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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. 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

  4. [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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. [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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. [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.

  13. 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 ...

  14. 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

  15. 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.

  16. [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.

  17. [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)

  18. 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

  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. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. [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.

  6. 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

  7. 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

  8. 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.

  9. 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 ...

  10. Management of hypersensivity pneumonitis

    PubMed Central

    2013-01-01

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

  11. 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

  12. 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

  13. 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.

  14. [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.

  15. 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.

  16. 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.

  17. 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...

  18. 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...

  19. 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.

  20. 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

  1. 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.

  2. [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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. Oral Hypersensitivity Reactions

    MedlinePlus

    ... often flavored with agents like cinnamon, peppermint or menthol, which can trigger hypersensitivity reactions in susceptible individuals. ... potential allergens such as cinnamon, peppermint, eugenol and menthol. Even dental floss and denture cleansers may contain ...

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. [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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  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. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. [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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

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

    SciTech Connect

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

    2011-06-01

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

  10. 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

  11. 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.

  12. 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... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall...

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

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Chlamydia Psittaci Vaccine (Feline... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall...

  14. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Chlamydia Psittaci Vaccine (Feline... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall...

  15. 9 CFR 113.71 - Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  16. 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... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall...

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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.

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

    PubMed Central

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

    2014-01-01

    Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used as an antidepressant. Interindividual variability and herb-drug interactions can lead to drug-induced toxicity. We report the case of a 35-year-old female patient diagnosed with synchronous pneumonitis and acute cardiomyopathy attributed to venlafaxine. The patient sought medical attention due to dyspnea and dry cough that started three months after initiating treatment with venlafaxine for depression. The patient was concomitantly taking Centella asiatica and Fucus vesiculosus as phytotherapeutic agents. Chest CT angiography and chest X-ray revealed parenchymal lung disease (diffuse micronodules and focal ground-glass opacities) and simultaneous dilated cardiomyopathy. Ecocardiography revealed a left ventricular ejection fraction (LVEF) of 21%. A thorough investigation was carried out, including BAL, imaging studies, autoimmune testing, right heart catheterization, and myocardial biopsy. After excluding other etiologies and applying the Naranjo Adverse Drug Reaction Probability Scale, a diagnosis of synchronous pneumonitis/cardiomyopathy associated with venlafaxine was assumed. The herbal supplements taken by the patient have a known potential to inhibit cytochrome P450 enzyme complex, which is responsible for the metabolization of venlafaxine. After venlafaxine discontinuation, there was rapid improvement, with regression of the radiological abnormalities and normalization of the LVEF. This was an important case of drug-induced cardiopulmonary toxicity. The circumstantial intake of inhibitors of the CYP2D6 isoenzyme and the presence of a CYP2D6 slow metabolism phenotype might have resulted in the toxic accumulation of venlafaxine and the subsequent clinical manifestations. Here, we also discuss why macrophage-dominant phospholipidosis was the most likely mechanism of toxicity in this case. PMID:25029655

  8. 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.

  9. 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%.

  10. 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.

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

    SciTech Connect

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

    2013-08-01

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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

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

    SciTech Connect

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

    2013-02-01

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

  5. 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.

  6. 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

  7. 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.

  8. 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%.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

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

    PubMed Central

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

    2015-01-01

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

  15. 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').

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. [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)

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. [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.

  20. 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.

  1. [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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  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. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  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. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. [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.

  4. [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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. [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.

  13. 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

  14. 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

  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. 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.

  17. Old, New and Hidden Causes of Perioperative Hypersensitivity.

    PubMed

    Garvey, Lene Heise

    2016-01-01

    Perioperative hypersensitivity reactions are rare, often life-threatening events, and subsequent investigations to identify the culprit are important to avoid re-exposure. All exposures in the perioperative setting may potentially be the cause of a hypersensitivity reaction, but drugs administered intravenously such as neuromuscular blocking agents (NMBA), induction agents and antibiotics have traditionally been reported to be implicated most commonly. It has recently become apparent that there are geographical differences in sensitization patterns related to variation in exposures, referral patterns and performance and interpretation of investigations. Differences in sensitization to NMBAs are partly explained by cross sensitization to pholcodine, an ingredient in cough-medicines available in some countries. While NMBAs are the most common causes of perioperative hypersensitivity in some countries, this may not necessarily be the case in all countries. New and hidden allergens have emerged as causes of perioperative hypersensitivity such as blue dyes, chlorhexidine and excipients. Detailed knowledge of the events at the time of reaction is necessary to identify potential culprits including rare and hidden allergens. Cooperation between allergists and anaesthetists, or other staff present perioperatively, is often needed to identify hidden or even undocumented exposures. The objectives of this review are to provide an overview of the history of investigation of perioperative hypersensitivity, to describe the differences in causes of perioperative hypersensitivity emerging over time and to increase awareness about the "hidden allergens" in the perioperative setting. Some practical advice on how to approach the patient testing negative on all initial investigations is also included.

  18. 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

  19. Pneumonic Plague

    MedlinePlus

    ... CDC.gov . Specific Hazards Bioterrorism A-Z Anthrax (Bacillus anthracis) Arenaviruses Treatment & Infection Control Specimen Submission & Lab Testing Education & Training Related Bioterrorism Resources Bacillus anthracis (Anthrax) Botulism (Clostridium botulinum toxin) Brucella species ( ...

  20. 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: ...

  1. 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

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

    PubMed Central

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

    1991-01-01

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

  3. 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

  4. 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.

  5. 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.

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

    PubMed

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

    2015-05-01

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

  7. 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.

  8. 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

  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. 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

  11. 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.

  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. 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

  14. Culicoides species attracted to horses with and without insect hypersensitivity.

    PubMed

    van der Rijt, Renske; van den Boom, Robin; Jongema, Yde; van Oldruitenborgh-Oosterbaan, Marianne M Sloet

    2008-10-01

    The aims of this study were to determine (1) which species of Culicoides is most commonly attracted to horses, (2) whether horses suffering insect hypersensitivity attract more Culicoides spp. than unaffected horses, and (3) the times when Culicoides spp. are most active. Horses affected by insect hypersensitivity and unaffected horses were placed inside mosquito netting tents for 30 min at different times of the day. All Culicoides spp. trapped inside the tents were collected and identified. C. obsoletus was the most common species found, followed by C. pulicaris. Healthy horses attracted slightly more midges than horses that were affected with insect hypersensitivity. All of the Culicoides species were most active at sunset, less so at sunrise and very few or no midges were trapped in the afternoon or at night.

  15. 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.

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

    PubMed Central

    Davari, AR; Ataei, E; Assarzadeh, H

    2013-01-01

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

  17. Clozapine-induced hypersensitivity myocarditis presenting as sudden cardiac death

    PubMed Central

    Balla, Sudarshan; Aggarwal, Kul

    2016-01-01

    Hypersensitivity myocarditis is a rare but serious adverse effect of clozapine, a commonly used psychiatric drug. We report the case of sudden cardiac death from clozapine-induced hypersensitivity myocarditis diagnosed at autopsy. A 54-year-old Caucasian male on clozapine therapy for bipolar disorder presented with a sudden onset of shortness of breath. Laboratory studies were significant for elevated N-terminal prohormone of brain natriuretic peptide. During his hospital stay, the patient died of sudden cardiac arrest from ventricular tachycardia. The autopsy revealed hypersensitivity myocarditis, which usually occurs in the first 4 weeks after the initiation of clozapine. A 4-week monitoring protocol, including laboratory assessment of troponin and C-reactive protein, may assist in the early diagnosis of this potentially fatal condition. PMID:28210568

  18. Contact hypersensitivity response to isophorone diisocyanate in mice

    SciTech Connect

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

    1989-09-01

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

  19. Efficacy of the UK Recombinant Plague Vaccine to Protect Against Pneumonic Plague in the Nonhuman Primate, Macaca Fascicularis (PRIVATE)

    DTIC Science & Technology

    2007-11-02

    septicaemic illness. This prese classical bubonic plague [2]. However, man-to-man transmission can occu nuclei spread by the coughing of patients with... bubonic or septicaemic plagu as the USP plague vaccine. A new sub-unit vaccine for plague has been rese developed at DSTL, Porton Down in the UK and...Efficacy of the UK recombinant plague vaccine to protect against pneumonic plague in the nonhuman primate, Macaca fascicularis {PRIVATE

  20. 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.

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

    PubMed

    Keohane, John; Quigley, Eamonn M M

    2006-05-07

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

  4. The hypersensitive esophagus: pathophysiology, evaluation, and treatment options.

    PubMed

    Remes-Troche, Jose M

    2010-10-01

    Visceral hypersensitivity plays a key role in the pathogenesis of esophageal functional disorders such as functional heartburn and chest pain of presumed esophageal origin (noncardiac chest pain). About 80% of patients with unexplained noncardiac chest pain exhibit lower esophageal sensory thresholds when compared to controls during esophageal sensory testing (ie, esophageal barostat, impedance planimetry). Such information has led to prescription of peripherally and/or centrally acting therapies for the management of these patients. This review summarizes and highlights recent and significant findings regarding the pathophysiology, evaluation, and treatment of the hypersensitive esophagus, a central factor in functional esophageal disorders.

  5. Acute kidney injury caused by zonisamide-induced hypersensitivity syndrome.

    PubMed

    Fujita, Yoshiro; Hasegawa, Midori; Nabeshima, Kuihiro; Tomita, Makoto; Murakami, Kazutaka; Nakai, Shigeru; Yamakita, Takashi; Matsunaga, Kayoko

    2010-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a severe adverse drug reaction affecting multiple organs caused by drug treatment. The current report describes a man who was prescribed zonisamide for epilepsy and subsequently developed widespread skin rash, acute kidney injury, high-grade fever, eosinophilia, liver dysfunction, lymphadenopathy and an increase in antihuman herpesvirus-6 immunoglobulin G titer. Hypersensitivity to zonisamide was confirmed by the skin patch test. Based on these findings, the patient was diagnosed with DRESS/DIHS caused by zonisamide. This is the first report of acute kidney injury due to zonisamide-induced DRESS/DIHS.

  6. Expression of a modified Mannheimia haemolytica GS60 outer membrane lipoprotein in transgenic alfalfa for the development of an edible vaccine against bovine pneumonic pasteurellosis.

    PubMed

    Lee, Raymond W H; Cornelisse, Mette; Ziauddin, Asma; Slack, Penelope J; Hodgins, Douglas C; Strommer, Judith N; Shewen, Patricia E; Lo, Reggie Y C

    2008-06-01

    The GS60 antigen is one of the protective antigens of Mannheimia haemolytica A1. GS60 contains conserved domains belonging to the LppC family of bacterial outer membrane lipoproteins. A high antibody titer to GS60 has been shown to be significantly correlated with resistance to pneumonic pasteurellosis. Calves vaccinated with a commercial vaccine (Presponse) and demonstrating protection against M. haemolytica A1 produced antibodies directed against GS60. Alfalfa was chosen as the platform for an edible vaccine. Agrobacterium tumefaciens was used to mediate the transformation of alfalfa with sequences encoding a slightly shortened derivative of the GS60 antigen (GS60(54)). Stable transgenic alfalfa lines were recovered and production of GS60(54) was examined by Western immunoblot analysis. The antigen is stable in dried transgenic plant material stored at ambient temperature for more than a year. The plant-produced GS60(54) protein was shown to be immunogenic when injected into rabbits. Feeding of the dried transgenic alfalfa expressing the GS60(54) to rabbits is capable of inducing seroconversion, suggesting that GS60(54) could be an effective oral antigen for stimulating mucosal immune responses.

  7. Pneumonitis in cancer patients receiving anti-PD-1 and radiotherapies

    PubMed Central

    Lu, Chieh-Sheng; Liu, Jin-Hwang

    2017-01-01

    Abstract Introduction: In development of novel therapies for the treatment of patient with cancer, the use of radiotherapy (RT) can produce significant local control and, in recent studies, has also been shown to mediate anti-tumor responses at distant sites by triggering and enhancing the endogenous cellular immune responses. Although RT induces an abscopal effect in some patients due to enhanced immune response to the tumor, immune-escape mechanisms, including up-regulation of programmed death-ligand 1 (PD-L1) on tumor cells, limit this benefit in other patients. Hence, many studies have promoted the synergy of RT and anti-programmed cell death protein 1 (PD-1) treatment for antitumor immunity. However, outcome may be improved when more therapies are combined, but risk of side effects can be increased. Case Presentation: We herein present 3 advanced cancer patients with pulmonary metastasis and who received RT. Later, they underwent anti-PD-1 treatment and unfortunately suffered from anti-PD-1-related pneumonitis over the nonirradiated areas after 4 cycles of treatment. The upregulation of cellular PD-1 expression in these areas was considered and the immune overreaction by anti-PD-1 treatment may cause these severe pulmonary adverse effects. Conclusion: Our review of 3 cases warrants careful workup to reduce the risk of side effects by combinative therapy with RT and anti-PD-1 treatment. PMID:28072716

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-10-01

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

  10. Nonspecific Interstitial Pneumonitis after Bortezomib and Thalidomide Treatment in a Multiple Myeloma Patient

    PubMed Central

    Kang, Wonseok; Kim, Jin Seok; Cho, Sang Ho; Kim, Sung Kyu; Chang, Joon

    2010-01-01

    Bortezomib, an inhibitor of 26S proteosome, is recently approved treatment option for multiple myeloma. Thalidomide, a drug with immunomodulating and antiangiogenic effects, has also shown promise as an effective treatment in multiple myeloma. Pulmonary complications are believed to be rare, especially interstitial lung disease. Here, we describe a patient with dyspnea and diffuse pulmonary infiltrates while receiving bortezomib and thalidomide in combination with dexamethasone for treatment-naïve multiple myeloma. Bronchoalveolar lavage demonstrated a significant decrease in the ratio of CD4 : CD8 T lymphocytes (CD4/8 ratio, 0.54). Extensive workup for other causes, including infections, was negative. A lung biopsy under video-assisted thorascopic surgery revealed a diagnosis of nonspecific interstitial pneumonitis. The symptoms and imaging study findings improved after initiating steroid treatment. Physicians should be aware of this potential complication in patients receiving the novel molecular-targeted antineoplastic agents, bortezomib and thalidomide, who present with dyspnea and new pulmonary infiltrates and fail to improve despite treatment with broad-spectrum antibiotics. PMID:20376900

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

    SciTech Connect

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

    1983-07-01

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

  12. Amiodarone pneumonitis: three further cases with a review of published reports.

    PubMed Central

    Darmanata, J I; van Zandwijk, N; Düren, D R; van Royen, E A; Mooi, W J; Plomp, T A; Jansen, H M; Durrer, D

    1984-01-01

    Three further patients are presented who developed evidence of a parenchymal pulmonary disturbance in the course of treatment with amiodarone. In one case the progress of the condition was rapid and ended fatally. Histological examination of the lungs showed evidence of diffuse alveolar damage. The concentration of amiodarone was from four to seven times higher in the lungs than in other organs studied. The concentration of the metabolite desethylamiodarone in the lungs was even higher in relation to other organs studied. The remaining two patients showed a more insidious onset and improvement after withdrawal of amiodarone and treatment with corticosteroids. Gallium 67 scintigraphy appeared to be a sensitive indicator of this adverse effect. Review of published reports revealed 35 cases of amiodarone pneumonitis, including the cases reported in this study. In 11 instances the dose of amiodarone was 400 mg or less. The onset was either insidious or rapidly progressive. Exertional dyspnoea was always present and a nonproductive cough, hypoxaemia, a raised erythrocyte sedimentation rate and diminished carbon monoxide diffusing capacity (transfer factor) were usually noted. Chest radiographs showed either a reticular pattern or diffuse patchy alveolar infiltrates. Discontinuation of amiodarone and an institution of corticosteroid treatment was usually followed by improvement or resolution. Images PMID:6695354

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

    SciTech Connect

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

    1983-08-01

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

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

    SciTech Connect

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

    2012-05-01

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

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

    PubMed Central

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

    2015-01-01

    Purpose To develop mitigators for combined irradiation to the lung and skin. Methods Rats were treated with X-rays as follows: (1) 12.5 or 13 Gy whole thorax irradiation (WTI) (2) 30 Gy soft X-rays to 10% area of the skin only (3) 12.5 or 13 Gy WTI+30 Gy skin irradiation after 3 hours (4) 12.5 Gy WTI+skin irradiation and treated with captopril (160 mg/m2/day) started after 7 days. Our end points were survival (primary) based on IACUC euthanization criteria and secondary measurements of breathing intervals and skin injury. Lung collagen at 210 days was measured in rats surviving 13 Gy WTI. Results After 12.5 Gy WTI with or without skin irradiation, one rat (12.5 Gy WTI) was euthanized. Survival was less than 10% in rats receiving 13 Gy WTI, but was enhanced when combined with skin irradiation (p<0.0001). Collagen content increased at 210 days after 13 Gy WTI vs 13 Gy WTI+30 Gy skin irradiation (p<0.05). Captopril improved radiation-dermatitis after 12.5 Gy WTI+30 Gy skin irradiation (p=0.008). Conclusions Radiation to the skin given 3 hours after WTI mitigated morbidity during pneumonitis in rats. Captopril enhanced the rate of healing of radiation-dermatitis after combined irradiations to the thorax and skin. PMID:24827855

  16. A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation

    PubMed Central

    Shi, Hua-shan; Gao, Xiang; Li, Dan; Zhang, Qiong-wen; Wang, Yong-sheng; Zheng, Yu; Cai, Lu-Lu; Zhong, Ren-ming; Rui, Ao; Li, Zhi-yong; Zheng, Hao; Chen, Xian-cheng; Chen, Li-juan

    2012-01-01

    Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application. PMID:22679371

  17. Trichloroethylene hypersensitivity syndrome: a disease of fatal outcome.

    PubMed

    Jung, Hyun Gul; Kim, Hyung Hun; Song, Bong Gun; Kim, Eun Jin

    2012-01-01

    Trichloroethylene is commonly used as an industrial solvent and degreasing agent. The clinical features of acute and chronic intoxication with trichloroethylene are well-known and have been described in many reports, but hypersensitivity syndrome caused by trichloroethylene is rarely encountered. For managing patients with trichloroethylene hypersensitivity syndrome, avoiding trichloroethylene and initiating glucocorticoid have been generally accepted. Generally, glucocorticoid had been tapered as trichloroethylene hypersensitivity syndrome had ameliorated. However, we encountered a typical case of trichloroethylene hypersensitivity syndrome refractory to high dose glucocorticoid treatment. A 54-year-old Korean man developed jaundice, fever, red sore eyes, and generalized erythematous maculopapular rashes. A detailed history revealed occupational exposure to trichloroethylene. After starting intravenous methylprednisolone, his clinical condition improved remarkably, but we could not reduce prednisolone because his liver enzyme and total bilirubin began to rise within 2 days after reducing prednisolone under 60 mg/day. We recommended an extended admission for complete recovery, but the patient decided to leave the hospital against medical advice. The patient visited the emergency department due to pneumonia and developed asystole, which did not respond to resuscitation.

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

    PubMed

    Potiwat, Rutcharin; Sitcharungsi, Raweerat

    2015-12-01

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

  19. Delayed-type hypersensitivity reaction against Nexplanon®.

    PubMed

    Serati, Maurizio; Bogani, Giorgio; Kumar, Sanjeev; Cromi, Antonella; Ghezzi, Fabio

    2015-01-01

    Nexplanon® is an etonogestrel implant with a long-acting contraceptive effect. Although several studies underlined its safety profile, its implant can rarely lead to moderate or severe adverse event. Here, we presented a case of delayed-type hypersensitivity reaction against Nexplanon® that resolved after its removal.

  20. [Post anthrax vaccine delayed hypersensitivity. II--delayed hypersensitivity in humans vaccinated against anthrax].

    PubMed

    Shlyakhov, E; Rubinstein, E

    1994-01-01

    To detect cell immunity characterized by delayed postvaccination hypersensitivity to anthrax in man and assess its dynamics, vaccination using unencapsulated live anthrax vaccine was performed in 668 healthy volunteers. Vaccination was performed either by scarification (n = 172), subcutaneous injection (n = 202), or low-dose (n = 202) or high-dose (n = 83) inhalation. The anthraxin intradermal tests were performed in each patient at various times during the year following vaccination (D7, D15, D90, D180, D365). This study confirm that, regardless of the mode of administration, the vaccine induces cell-mediated immunity in man, as determined by positive anthraxine skin test. The incidence of positive tests decreases with time regardless of the mode of vaccination. After one year, the test remained positive in 34.8% of subjects vaccinated by subcutaneous injection, 37.5% vaccinated by low-dose inhalation, 34.2% vaccinated by high-dose inhalation, and 22.4% vaccinated by scarification. These findings are in agreement with those obtained in clinical epidemiological studies documenting the effectiveness of encapsulated live anthrax vaccine in man.

  1. Application of Diode Laser in the Treatment of Dentine Hypersensitivity

    PubMed Central

    Gojkov-Vukelic, Mirjana; Hadzic, Sanja; Zukanovic, Amila; Pasic, Enes; Pavlic, Veriva

    2016-01-01

    Introduction: Dentine hypersensitivity is characterized by acute, sharp pain arising from the exposed dentine, most commonly in response to thermal, tactile, or chemical stimuli, and which cannot be linked to any other pathological changes in the tooth or the environment. Therapy uses various impregnating agents in the form of solutions or gels and, in more recent times, laser. Aim: The aim of this research was to examine the effects of treatment of hypersensitive dental cervix with diode laser. Materials and Methods: The study included 18 patients with 82 sensitive teeth. The degree of dentine hypersensitivity was evaluated by visual analogue scale (VAS), and the treatment was carried out by application of low-power diode laser over the span of three visits, which depended on the initial sensitivity. Results: There is a significant difference in VAS values measured at the onset of treatment (baseline) and immediately after the first laser treatment (t=9.275; p=0.000), after 7 days, after the second laser treatment (14 days) (t=7.085, p=0.000), as well as after 14 days and the third laser treatment (t=5.517, p=0.000), which confirms the effectiveness of this therapeutic procedure. The results showed a reduction of hypersensitivity in response to tactile stimulus with a probe after the third treatment, even with teeth whose value on the VAS was very high at the beginning of treatment (baseline). Conclusion: Within the scope of the conducted study, laser therapy has provided extremely safe and effective results in the treatment of cervical dentine hypersensitivity. PMID:28210023

  2. Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood

    PubMed Central

    Yi, Lisha; Zhang, Haiqin; Sun, Huihui; Zhou, Lu; Chen, Ying; Xuan, Liqian; Jiang, Yuanxi; Xu, Shuchang

    2017-01-01

    Background/Aims Early adverse life events (EALs) are relevant to irritable bowel syndrome in adulthood. Maternal separation (MS), as one of the EALs, has proved to induce visceral hypersensitivity in adult rats. However, the effect of MS on visceral hypersensitvity from the post-weaning period to adulthood remains unknown. Methods One hundred and ten neonatal Sprague-Dawley rats were randomly divided into 2 groups: rats in the MS group were exposed to 3 hours daily MS on postnatal day (PND) 2–14; the normal control (NC) group remained undisturbed. Visceral sensitivity was determined by measuring the visceromotor response to colorectal distention on PND21, 35, and 56. Anxiety-like behaviors were measured by the open field test. Results Compared with NC rats, MS rats showed significant visceral hypersensitivity from the post-weaning period to adult. The proportion of visceral hypersensitive rats decreased with age from 87.5% to 70.0% in the female MS group and from 90.0% to 66.7% in the male MS group. The relative VMR ratio of MS and NC on PND21 was higher than PND35 and PND56. MS rats showed decreased ability of movement and exploration to the novel environment in the post-weaning period, obesity in the prepubertal period, and more anxiety-like behaviors in adulthood. Conclusions MS can significantly affect visceral sensitivity and behaviors of rats in different age stages, especially in the post-weaning period. Visceral hypersensitivity of MS rats is more pronounced in the post-weaning period and slightly restored in adults. Thus, visceral hypersensitivity in the post-weaning period might play a more meaningful pathophysiologic role in the formation of adult irritable bowel syndrome. PMID:28238254

  3. Estrogen-dependent visceral hypersensitivity following stress in rats

    PubMed Central

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

    2016-01-01

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

  4. Delayed-type hypersensitivity and immunoglobulin E in American cutaneous leishmaniasis.

    PubMed Central

    Lynch, N R; Yarzábal, L; Verde, O; Avila, J L; Monzon, H; Convit, J

    1982-01-01

    Delayed-type hypersensitivity (DTH) and both total and specific immunoglobulin E (IgE) antibody levels were studied during an outbreak of American cutaneous leishmaniasis. Direct correlations were detected between DTH reactivity and either age or the period of evolution of the infection, and a clear association with sex (strongest response in females) was observed. Extremely high, age-dependent, total serum IgE levels were measured in the study group, probably due to concurrent intestinal helminthiasis. A low proportion of the group also had detectable levels of specific anti-Leishmania IgE antibody. Total and specific IgE levels were also sex dependent (lowest in females), and an inverse correlation was found between these levels and DTH responsiveness, possibly reflecting the intervention of regulatory influences of T-lymphocyte activity. PMID:7152676

  5. Drug-induced pneumonitis detected earlier by 18F-FDG-PET than by high-resolution CT: a case report with non-Hodgkin's lymphoma.

    PubMed

    Yamane, Tomohiko; Daimaru, Osami; Ito, Satoshi; Nagata, Takeshi; Yoshiya, Kazuhiko; Fukaya, Nobuyuki; Ito, Shinichi; Imai, Teruhiko; Uchida, Hideo

    2008-10-01

    Drug-induced pneumonitis is a serious and an unpredictable side effect of chemotherapy in patients with malignant lymphoma. We present the case of a 51-year-old man who developed drug-induced pneumonitis during chemotherapy for non-Hodgkin's lymphoma in which pneumonitis was detected earlier by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) than by high-resolution computed tomography (HRCT). After five courses of chemotherapy, 18F-FDG-PET was performed for assessing residual lesions, and diffuse lung uptake was incidentally observed. No symptoms were present, and HRCT performed immediately following PET revealed no abnormalities. Mild dyspnea appeared 3 days after PET, and additional HRCT revealed patchy ground-glass opacities disseminated with the appearance of interlobular septum thickening. Drug-induced pneumonitis was finally diagnosed, and treatment was initiated. 18F-FDG-PET can be an imaging modality for detecting drug-induced pneumonitis at an extremely early stage in which HRCT is incapable of revealing any abnormal changes.

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

    PubMed Central

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

    2015-01-01

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

  7. Effects of palmitoylethanolamide on the cutaneous allergic inflammatory response in Ascaris hypersensitive Beagle dogs.

    PubMed

    Cerrato, Santiago; Brazis, Pilar; Della Valle, Maria Federica; Miolo, Alda; Petrosino, Stefania; Di Marzo, Vincenzo; Puigdemont, Anna

    2012-03-01

    Palmitoylethanolamide (PEA) is an endogenous lipid mediator with anti-inflammatory and anti-hyperalgesic properties. The main objective of the present study was to evaluate the effects of PEA on the cutaneous allergic inflammatory reaction induced by different immunological and non-immunological stimuli in hypersensitive dogs. Six spontaneously Ascaris hypersensitive Beagle dogs were challenged with intradermal injections of Ascaris suum extract, substance P and anti-canine IgE, before and after a single oral administration of PEA at doses of 3, 10 and 30 mg/kg. A significant reduction in wheal area induced by both antigen and anti-canine IgE challenge was observed after PEA administration. No significant differences were observed between the two higher doses studied, suggesting that the 10 mg/kg dose had exerted the maximum inhibitory effect. When blood levels of PEA were compared with the effects at different times, an evident correlation was obtained. However, the anti-inflammatory effects of PEA were more long-lasting than their plasma concentrations. The intradermal injection of substance P did not reveal any skin reaction (wheal or erythema formation) at any of the concentrations tested. In conclusion, PEA might constitute a new therapeutic strategy for the treatment of allergic inflammatory skin diseases in companion animals.

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

    PubMed

    Otani, Iris M; Banerji, Aleena

    2016-03-01

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

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

    SciTech Connect

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

    Early identification of impending illness during widespread exposure to a pathogenic agent offers a potential means to initiate treatment during a timeframe when it would be most likely to be effective and has the potential to identify novel therapeutic strategies. The latter could be critical, especially as antibiotic resistance is becoming widespread. In order to examine pre-symptomatic illness, African green monkeys were challenged intranasally with aerosolized Yersinia pestis strain CO92 and blood samples were collected in short intervals from 45 m till 42 h post-exposure. Presenting one of the first genomic investigations of a NHP model challenged by pneumonic plague, whole genome analysis was annotated in silico and validated by qPCR assay. Transcriptomic profiles of blood showed early perturbation with the number of differentially expressed genes increasing until 24 h. By then, Y. pestis had paralyzed the host defense, as suggested by the functional analyses. Early activation of the apoptotic networks possibly facilitated the pathogen to overwhelm the defense mechanisms, despite the activation of the pro-inflammatory mechanism, toll-like receptors and microtubules at the port-of-entry. The overexpressed transcripts encoding an early pro-inflammatory response particularly manifested in active lymphocytes and ubiquitin networks were a potential deviation from the rodent models, which needs further verification. In summary, the present study recognized a pattern of Y. pestis pathogenesis potentially more applicable to the human system. Independent validation using the complementary omics approach with comprehensive evaluation of the organs, such as lungs which showed early bacterial infection, is essential. PMID:27003632

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

    SciTech Connect

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

    2010-08-01

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

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

    SciTech Connect

    Krafft, S; Briere, T; Court, L; Martel, M

    2015-06-15

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

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

    SciTech Connect

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

    2013-03-01

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

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

    SciTech Connect

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

    2015-08-15

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

  15. A severe hypersensitivity reaction to abacavir following re-challenge.

    PubMed

    Todd, Sej; Emerson, C R

    2017-03-01

    We report this case to highlight the possibility of a severe hypersensitivity reaction as an important potential consequence of couples, living with HIV, sharing anti-retroviral treatment. An HIV-1 positive and carrier of HLA-B*57:01 allele, treatment experienced man was commenced one pill Regimen Stribild (tenofovir, emtricitabine, elvitegravir and cobicistat) in July 2015. On running short of medication, he admitted to sharing his partner's treatment (Triumeq; abacavir, lamivudine and dolutegravir). On the second occasion, re-introduction resulted in whole body rash 4 h post dose and was associated with fever, respiratory symptoms, headache and vomiting. On examination, he was pyrexic, tachyponeic, tachycardiac and hypotensive. Hypersensitivity to abacavir can cause significant morbidity. Re-challenge can result in a more rapid, severe and potentially life-threatening reaction. This potentially could become an increasing problem with more couples, living with HIV, sharing medication.

  16. Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions

    PubMed Central

    Böhm, Ruwen; Cascorbi, Ingolf

    2016-01-01

    Adverse drug reactions adverse drug reaction (ADR) occur in approximately 17% of patients. Avoiding ADR is thus mandatory from both an ethical and an economic point of view. Whereas, pharmacogenetics changes of the pharmacokinetics may contribute to the explanation of some type A reactions, strong relationships of genetic markers has also been shown for drug hypersensitivity belonging to type B reactions. We present the classifications of ADR, discuss genetic influences and focus on delayed-onset hypersensitivity reactions, i.e., drug-induced liver injury, drug-induced agranulocytosis, and severe cutaneous ADR. A guidance how to read and interpret the contingency table is provided as well as an algorithm whether and how a test for a pharmacogenetic biomarker should be conducted. PMID:27818635

  17. Hypersensitivity with Inhalational Budesonide: An Under Recognised Entity

    PubMed Central

    Sharma, Pramod Kumar; Hasan, Najmul; Krishnamurthy, Bhaskar; Singh, Surjit

    2016-01-01

    Hypersensitivity reactions are commonly encountered with drugs such as beta lactams, sulphonamides, allopurinol etc., Corticosteroids are frequently employed in the treatment of drug induced allergic reactions. Therefore, it is highly unlikely that a corticosteroid itself may cause such a reaction as an adverse effect. We had encountered a rare case of hypersensitivity reaction with inhalational budesonide in an eight-year-old boy. The patient developed maculopapular rashes over the back, buttocks and legs accompanied with pruritus within four hours of administration of the first dose. The reaction subsided within two days on withdrawal of the drug and treatment with oral fexofenadine. Re-introduction of budesonide by the same route after a month resulted in appearance of similar reaction. Both the parents of the patient were known cases of allergic rhinitis suggesting allergic pre-disposition in the family. Causality analysis using WHO-UMC scale suggested certain association of this allergic reaction with inhaled budesonide. PMID:27891350

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

    PubMed Central

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

    2015-01-01

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

  19. [Hypersensitivity in patients with Hebra's prurigo caused by flea bite].

    PubMed

    De Almeida, F A; Croce, J

    1990-01-01

    The authors present a study of hypersensitivity of patients with Hebra's prurigo (HP) to feleabites. Thirty six patients were studied. With the results obtained the following conclusions are held: 1. Among the probable responsible factors found in the history of patients with HP, the flea bite is the principal factor. 2. Almost all the patients with HP who were studied show hypersensitivity to flea bites. 3. With the flea bites on the patients with HP, one can observe the clinical and histopathology similarity of both the experimental and elementary lesions of the disease. 4. It was possible to show humoral antibodies in the serum of the patients with HP immunodiffusion technique to the 1:40 flea extract.

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

    PubMed

    Venter, Carina

    2009-01-01

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

  1. Hypersensitive reaction to praziquantel in a clonorchiasis patient.

    PubMed

    Lee, Jung-Min; Lim, Hyun-Sul; Hong, Sung-Tae

    2011-09-01

    Praziquantel is the drug of choice for clonorchiasis. Since clonorchiasis is endemic in most river basins, praziquantel has been widely used for 30 years in Korea. A 54-year-old Korean woman suffered from hypersensitive reactions, such as nausea, dyspnea, rash, and urticaria after taking the first dose of praziquantel to treat clonorchiasis. She ingested one dose again and the same symptoms appeared, and she was treated at a clinic with anti-histamines. She tried one more dose with anti-histamines but found the same symptoms. Later, she was found to pass eggs of Clonorchis sinensis and medicated with flubendazole. The hypersensitive reaction to praziquantel is rare but occurs. This is the 5th case report in the world.

  2. The Hypersensitivity of Horses to Culicoides Bites in British Columbia

    PubMed Central

    Anderson, Gail S.; Belton, Peter; Kleider, Nicholas

    1988-01-01

    Culicoides hypersensitivity is a chronic, recurrent, seasonal dermatitis of horses that has a worldwide distribution, but has only recently been reported in Canada. It is characterized by intense pruritus resulting in lesions associated with self-induced trauma. A survey of veterinarians and horse-owners in British Columbia showed no differences in susceptibility due to the sex, color, breed, or height of the horses. The prevalence of the disease in the 209 horses surveyed was 26%. Horses sharing the same pasture could be unaffected. The disease was reported primarily from southwestern British Columbia; it occurred between April and October and usually affected the ventral midline, mane, and tail. Horses were generally less than nine years old when the clinical signs first appeared ([unk]=5.9 yr). Culicoides hypersensitivity was common in the lineage of several affected horses, possibly indicating a genetic susceptibility. Most cases were severe enough to require veterinary attention and some horses were euthanized. PMID:17423117

  3. Allopurinol hypersensitivity reactions: desensitization strategies and new therapeutic alternative molecules.

    PubMed

    Calogiuri, Gianfranco; Nettis, Eustachio; Di Leo, Elisabetta; Foti, Caterina; Ferrannini, Antonio; Butani, Lavjay

    2013-02-01

    Allopurinol, an analog of hypoxanthine has been worldwide used for the treatment of hyperuricemia and gout for over 40 years. Unfortunately some patients assuming this medication have developed hypersensitivity reactions ranging from mild cutaneous eruption to more severe clinical manifestations such as allopurinol hypersensitivity syndrome or Steven-Johnson syndrome and lethal toxic epidermal necrolysis. Various strategies of slow desensitization have been elaborated to reintroduce allopurinol in a part of these patients, mainly patients affected by mild skin reactions as fixed drug eruption or exanthema. However, several new uricosuric therapies have been recently introduced. Actually drugs as recombinant urate oxidase and febuxostat are under post-marketing surveillance to control potential adverse effects related to their immunogenicity even.

  4. The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders.

    PubMed

    Farmer, Adam D; Ruffle, James K; Aziz, Qasim

    2017-02-01

    The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.

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

    PubMed Central

    Zakrzewski, Aleksander; Matuszewski, Tomasz; Kruszewski, Jerzy

    2013-01-01

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

  6. Carbimazole-associated hypersensitivity vasculitis in a cat.

    PubMed

    Bowlt, K; Cattin, I; Stewart, J

    2014-12-01

    Feline hyperthyroidism can be treated medically, surgically or with radioactive iodine. Carbimazole inhibits both triiodothyronine and thyroxine synthesis in the thyroid gland and reported side effects include mild eosinophilia, leucopenia and lymphocytosis, thrombocytopenia, elevated liver enzyme activities, gastrointestinal signs and skin abnormalities. This case report describes a cat with carbimazole-associated apparent hypersensitivity vasculitis causing digital and tail necrosis, with multiple renal infarcts. Withdrawal of carbimazole resulted in stable disease.

  7. [Allopurinol hypersensitivity syndrome. A report of two cases].

    PubMed

    Rodríguez-Arámbula, Adriana; Arenas-Velázquez, Elsa; Castanedo-Cázares, Juan Pablo; Hernández-Blanco, Diana; Oros-Ovalle, Cuauhtémoc; Torres-Álvarez, Bertha

    2016-01-01

    Patients in treatment with allopurinol are in risk of having life threatening adverse reactions particularly at the beginning of the treatment. Two percent of the patients prescribed with this drug have associated severe cutaneous adverse reactions. We present two cases of allopurinol hypersensitivity syndrome in mexican patients in which asymptomatic hyperuricemia was the indication to its use. The general physician and the specialist must be alert of this syndrome that causes elevate morbidity and mortality.

  8. Genome-wide analysis links NFATC2 with asparaginase hypersensitivity

    PubMed Central

    Fernandez, Christian A.; Smith, Colton; Yang, Wenjian; Mullighan, Charles G.; Qu, Chunxu; Larsen, Eric; Bowman, W. Paul; Liu, Chengcheng; Ramsey, Laura B.; Chang, Tamara; Karol, Seth E.; Loh, Mignon L.; Raetz, Elizabeth A.; Winick, Naomi J.; Hunger, Stephen P.; Carroll, William L.; Jeha, Sima; Pui, Ching-Hon; Evans, William E.; Devidas, Meenakshi

    2015-01-01

    Asparaginase is used to treat acute lymphoblastic leukemia (ALL); however, hypersensitivity reactions can lead to suboptimal asparaginase exposure. Our objective was to use a genome-wide approach to identify loci associated with asparaginase hypersensitivity in children with ALL enrolled on St. Jude Children’s Research Hospital (SJCRH) protocols Total XIIIA (n = 154), Total XV (n = 498), and Total XVI (n = 271), or Children’s Oncology Group protocols POG 9906 (n = 222) and AALL0232 (n = 2163). Germline DNA was genotyped using the Affymetrix 500K, Affymetrix 6.0, or the Illumina Exome BeadChip array. In multivariate logistic regression, the intronic rs6021191 variant in nuclear factor of activated T cells 2 (NFATC2) had the strongest association with hypersensitivity (P = 4.1 × 10−8; odds ratio [OR] = 3.11). RNA-seq data available from 65 SJCRH ALL tumor samples and 52 Yoruba HapMap samples showed that samples carrying the rs6021191 variant had higher NFATC2 expression compared with noncarriers (P = 1.1 × 10−3 and 0.03, respectively). The top ranked nonsynonymous polymorphism was rs17885382 in HLA-DRB1 (P = 3.2 × 10−6; OR = 1.63), which is in near complete linkage disequilibrium with the HLA-DRB1*07:01 allele we previously observed in a candidate gene study. The strongest risk factors for asparaginase allergy are variants within genes regulating the immune response. PMID:25987655

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

    PubMed

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

    1996-01-01

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

  10. Immediate hypersensitivity reactions to penicillins and other betalactams.

    PubMed

    Antúnez, C; Martín, E; Cornejo-García, J A; Blanca-Lopez, N; R-Pena, R; Mayorga, C; Torres, M J; Blanca, M

    2006-01-01

    Immediate hypersensitivity reactions to betalactams are IgE mediated and constitute the most frequent allergic reactions mediated by specific immunological mechanisms. IgE responses to benzyl penicillin (BP), the first antibiotic producing the benzyl penicilloyl structure (BPO), are characterized by a quick release of inflammatory mediators, resulting in anaphylactic shock, urticaria and angioedema. With the progressive appearance of other structures, comprising cephalosporins, carbapenems, monobactams and clavulanic acid, IgE selective responses and cross-reactivity reactions were observed. The diagnosis of betalactam hypersensitivity, classically based on skin testing with major and minor determinants of benzyl penicillin or in vitro IgE antibodies to BP, has been modified by the inclusion of different determinants generated from these compounds, for which amoxicillin (AX) is the most relevant, followed by cephalosporins. Some subjects develop positive responses to several betalactams, mostly within the same family, but others develop a selective response. These are relevant for the appropriate selection of antimicrobial drugs in patients who have immediate hypersensitivity to betalactams.

  11. Type I hypersensitivity reaction as a complication of lepa

    PubMed Central

    Janthli, Deepa Manjunath; Chaturvedi, Ashutosh; Somashekar, Shruthi; Lohith, B. A.

    2015-01-01

    Adverse drug reaction is defined as response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological functions. Type I hypersensitivity reaction is known as anaphylactic reaction which is due to immediate immunoglobulin E-mediated reaction. It is characterized by symptoms such as fever nausea, back pain, angiodema, rash, flushing, etc. Lepa generally refers to the application of pastes formed by mixing powder of herbs with water, milk, etc., and liquids. Complementary and alternative medicines are frequently used by the general population. Many people consider them to be without side effects. Ayurvedic treatment involves Shodhana (biopurification), Shaman (pacification), Bahya (external therapy), and Abhyantara karma's (internal therapy) for treating different diseases. One such bahya karma or external therapy is lepa. Even though lepa is said as “Aadhya Upakrama,” undue hypersensitivity is observed in many patients. A 60-year-old woman had an adverse reaction to lepa after being administered as an external medication. The observations were erythema, eruptions, and itching. Such case of hypersensitivity is discussed in the present study. PMID:26792959

  12. Ozone Treatment on Dentin Hypersensitivity Surfaces – A Pilot Study

    PubMed Central

    Lena, Karlsson; Marianne, Kjaeldgaard

    2017-01-01

    Background: Dentin hypersensitivity (DH) is a frequent condition in adults and difficult to treat. The aim of this single-blind, randomised controlled clinical trial was to investigate immediate and long-term effect of ozone treatment (Prozone, W&H NORDIC AB) for 12 seconds on hypersensitive teeth compared to placebo treatment, using a split-mouth design. Methods: 26 patients (12 M, 14 F, mean age 44+ 2) were included in the study having at least two teeth with confirmed DH in different quadrants of the dentition (each subject had one test and one control tooth). A visual analogue scale (VAS) was used to measure the patients´ pain perception immediately and at a long-term follow-up three months later. Results: Significant reduction in pain perception from DH surfaces was demonstrated from ozone treated test teeth as well as in placebo treated control teeth. We found a moderate (16.2%) but significant pain relief (p< 0.012) over time in 57.7% of all treated teeth. Conclusion: Results from this study confirm previously published results showing no significant effect of ozone treatment on hypersensitive teeth compared to placebo treatment. PMID:28356999

  13. Type I hypersensitivity reaction as a complication of lepa.

    PubMed

    Janthli, Deepa Manjunath; Chaturvedi, Ashutosh; Somashekar, Shruthi; Lohith, B A

    2015-12-01

    Adverse drug reaction is defined as response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological functions. Type I hypersensitivity reaction is known as anaphylactic reaction which is due to immediate immunoglobulin E-mediated reaction. It is characterized by symptoms such as fever nausea, back pain, angiodema, rash, flushing, etc. Lepa generally refers to the application of pastes formed by mixing powder of herbs with water, milk, etc., and liquids. Complementary and alternative medicines are frequently used by the general population. Many people consider them to be without side effects. Ayurvedic treatment involves Shodhana (biopurification), Shaman (pacification), Bahya (external therapy), and Abhyantara karma's (internal therapy) for treating different diseases. One such bahya karma or external therapy is lepa. Even though lepa is said as "Aadhya Upakrama," undue hypersensitivity is observed in many patients. A 60-year-old woman had an adverse reaction to lepa after being administered as an external medication. The observations were erythema, eruptions, and itching. Such case of hypersensitivity is discussed in the present study.

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

    PubMed Central

    Black, L.; Pay, T. W.

    1975-01-01

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

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

    PubMed

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

    2008-10-01

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

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

    SciTech Connect

    Gordon, J; Snyder, K; Zhong, H; Chetty, I

    2014-06-01

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

  17. Effects of positioning uncertainty and breathing on dose delivery and radiation pneumonitis prediction in breast cancer.

    PubMed

    Mavroidis, Panayiotis; Axelsson, Sofie; Hyödynmaa, Simo; Rajala, Juha; Pitkänen, Maunu A; Lind, Bengt K; Brahme, Anders

    2002-01-01

    The quality of the radiation therapy delivered in the treatment of breast cancer is susceptible to setup errors and organ motion uncertainties. For 60 breast cancer patients (24 resected with negative node involvement, 13 resected with positive node involvement and 23 ablated) who were treated with three different irradiation techniques. these uncertainties are simulated. The delivered dose distributions in the lung were recalculated taking positioning uncertainty and breathing effects into account. In this way the real dose distributions delivered to the patients are more closely determined. The positioning uncertainties in the anteroposterior (AP) and the craniocaudal (CC) directions are approximated by Gaussian distributions based on the fact that setup errors are random. Breathing is assumed to have a linear behavior because of the chest wall movement during expiration and inspiration. The combined frequency distribution of the positioning and breathing distributions is obtained by convolution. By integrating the convolved distribution over a number of intervals, the positions and the weights of the fields that simulate the original 'effective fields' are calculated. Opposed tangential fields are simulated by a set of 5 pairs of fields in the AP direction and 3 such sets in the CC direction. Opposed AP + PA fields are simulated by a set of 3 pairs of fields in the AP direction and 3 such sets in the CC direction. Single frontal fields are simulated by a set of 5 fields. In radiotherapy for breast cancer, the lung is often partly within the irradiated volume even though it is a sensitive organ at risk. The influence of the deviation in the dose delivered by the original and the adjusted treatment plans on the clinical outcome is estimated by using the relative seriality model and the biologically effective uniform dose concept. Radiation pneumonitis is used as the clinical endpoint for lung complications. The adjusted treatment plans show larger lung

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

    SciTech Connect

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

    2005-11-01

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

  19. Type IV hypersensitivity reactions following Dermabond adhesive utilization in knee surgery: A Report of Three Cases.

    PubMed

    Yagnatovsky, Michelle; Pham, Hien; Rokito, Andrew; Jazrawi, Laith; Strauss, Eric

    2017-01-25

    ​We retrospectively reviewed the records of 3 patients (3 knees) with a delayed type hypersensitivity reaction following Dermabond exposure after an orthopaedic knee procedure. Delayed hypersensitivity reactions are mediated by CD4+ helper T cells. The use of skin adhesives in place of traditional sutures is increasing in popularity given Dermabond's potential benefits of decreased wound infection rate and better wound approximation. However, hypersensitivity reactions to the cyanoacrylate material in Dermabond have been described. Differentiating hypersensitivity reactions from post-operative infections is important as septic arthritis is a potentially devastating complication. This case series presents the challenge of properly diagnosing and managing hypersensitivity reactions. Consultation with allergists and dermatologists may be appropriate for ascertaining the nature of the surgical site complication and proper management. The recommended management of hypersensitivity-type reactions is a course of topical steroids and infection work up if needed.

  20. Hypersensitivity to ticagrelor and low response to clopidogrel: a case report

    PubMed Central

    Dai, Jing; Ge, Changjiang

    2017-01-01

    Ticagrelor is widely used to treat acute coronary syndrome. Hypersensitivity reaction of ticagrelor is rarely recognized. A low response to clopidogrel, which occurs in up to 23% of patients, is an independent risk factor for stent thrombosis. Management of patients with a low response to clopidogrel and ticagrelor hypersensitivity who are undergoing antithrombotic therapy remains to be a challenge. Herein, we report a patient with low response to clopidogrel and ticagrelor hypersensitivity, who was successfully managed using aspirin and warfarin. PMID:28154807

  1. Prevalence of dentine hypersensitivity: A cross-sectional study in rural Punjabi Indians

    PubMed Central

    Dhaliwal, Jagjit Singh; Palwankar, Pooja; Khinda, Paramjit K.; Sodhi, Sachinjeet K.

    2012-01-01

    Aims and Objectives: To study the prevalence of dentine hypersensitivity and related risk factors in rural population of Punjab, India. Materials and Methods: A total of 650 subjects reporting dentine sensitivity were included in the study comprising of 270 males and 380 females. All the subjects completed an interview and the subjects reporting dentine hypersensitivity were examined further using air syringe to put a blast of air to confirm the diagnosis of dentine hypersensitivity. Periodontal attachment loss and gingival recession of all the sensitive teeth were examined and recorded. Results: The prevalence of dentine hypersensitivity was 25% in the oral test. The subjects receiving the treatment of hypersensitivity were only 15.1%. The older group in the 50-59 years had the highest number (98%) of subjects with dentine hypersensitivity. Most commonly affected teeth were mandibular incisors. The other factors related to dentine hypersensitivity were the socioeconomic status, lower education level, and access to dental care. The periodontal factors related to hypersensitivity were gingival recession and poor oral hygiene. Conclusions: The prevalence of dentine hypersensitivity was 25% in the rural population of Punjab. PMID:23162341

  2. New insights into visceral hypersensitivity —clinical implications in IBS

    PubMed Central

    Zhou, QiQi; Verne, G. Nicholas

    2012-01-01

    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. PMID:21643039

  3. Peripheral NMDA Receptors Mediate Antidromic Nerve Stimulation-Induced Tactile Hypersensitivity in the Rat.

    PubMed

    Jang, Jun Ho; Nam, Taick Sang; Jun, Jaebeom; Jung, Se Jung; Kim, Dong-Wook; Leem, Joong Woo

    2015-01-01

    We investigated the role of peripheral NMDA receptors (NMDARs) in antidromic nerve stimulation-induced tactile hypersensitivity outside the skin area innervated by stimulated nerve. Tetanic electrical stimulation (ES) of the decentralized L5 spinal nerve, which induced enlargement of plasma extravasation, resulted in tactile hypersensitivity in the L4 plantar dermatome of the hind-paw. When intraplantar (i.pl.) injection was administered into the L4 dermatome before ES, NMDAR and group-I metabotropic Glu receptor (mGluR) antagonists and group-II mGluR agonist but not AMPA/kainate receptor antagonist prevented ES-induced hypersensitivity. I.pl. injection of PKA or PKC inhibitors also prevented ES-induced hypersensitivity. When the same injections were administered after establishment of ES-induced hypersensitivity, hypersensitivity was partially reduced by NMDAR antagonist only. In naïve animals, i.pl. Glu injection into the L4 dermatome induced tactile hypersensitivity, which was blocked by NMDAR antagonist and PKA and PKC inhibitors. These results suggest that the peripheral release of Glu, induced by antidromic nerve stimulation, leads to the expansion of tactile hypersensitive skin probably via nociceptor sensitization spread due to the diffusion of Glu into the skin near the release site. In addition, intracellular PKA- and PKC-dependent mechanisms mediated mainly by NMDAR activation are involved in Glu-induced nociceptor sensitization and subsequent hypersensitivity.

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

    PubMed Central

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

    2014-01-01

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

  5. Hypersensitivity reaction to high-dose methotrexate and successful rechallenge in a pediatric patient with osteosarcoma.

    PubMed

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

    2014-02-01

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

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

    PubMed

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

    2016-01-01

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

  7. Hypersensitivity of excitation-contraction coupling in dystrophic cardiomyocytes

    PubMed Central

    Ullrich, Nina D.; Fanchaouy, Mohammed; Gusev, Konstantin; Shirokova, Natalia

    2009-01-01

    Duchenne muscular dystrophy represents a severe inherited disease of striated muscle. It is caused by a mutation of the dystrophin gene and characterized by a progressive loss of skeletal muscle function. Most patients also develop a dystrophic cardiomyopathy, resulting in dilated hypertrophy and heart failure, but the cellular mechanisms leading to the deterioration of cardiac function remain elusive. In the present study, we tested whether defective excitation-contraction (E-C) coupling contributes to impaired cardiac performance. “E-C coupling gain” was determined in cardiomyocytes from control and dystrophin-deficient mdx mice. To this end, L-type Ca2+ currents (ICaL) were measured with the whole cell patch-clamp technique, whereas Ca2+ transients were simultaneously recorded with confocal imaging of fluo-3. Initial findings indicated subtle changes of E-C coupling in mdx cells despite matched Ca2+ loading of the sarcoplasmic reticulum (SR). However, lowering the extracellular Ca2+ concentration, a maneuver used to unmask latent E-C coupling problems, was surprisingly much better tolerated by mdx myocytes, suggesting a hypersensitive E-C coupling mechanism. Challenging the SR Ca2+ release by slow elevations of the intracellular Ca2+ concentration resulted in Ca2+ oscillations after a much shorter delay in mdx cells. This is consistent with an enhanced Ca2+ sensitivity of the SR Ca2+-release channels [ryanodine receptors (RyRs)]. The hypersensitivity could be normalized by the introduction of reducing agents, indicating that the elevated cellular ROS generation in dystrophy underlies the abnormal RyR sensitivity and hypersensitive E-C coupling. Our data suggest that in dystrophin-deficient cardiomyocytes, E-C coupling is altered due to potentially arrhythmogenic changes in the Ca2+ sensitivity of redox-modified RyRs. PMID:19783774

  8. Microglia: a newly discovered role in visceral hypersensitivity?

    PubMed Central

    Saab, Carl Y.; Wang, Jing; Gu, Chunping; Garner, Kirsten N.; Al-Chaer, Elie D.

    2007-01-01

    Given the growing body of evidence for a role of glia in pain modulation, it is plausible that the exaggerated visceral pain in chronic conditions might be regulated by glial activation. In this study, we have investigated a possible role for microglia in rats with chronic visceral hypersensitivity and previously documented altered neuronal function. Experiments were performed on adult male Sprague-Dawley rats pre-treated with neonatal colon irritation (CI) and on control rats. Effects of fractalkine (FKN, a chemokine involved in neuron-to-microglia signaling) and of minocycline (an inhibitor of microglia) on visceral sensitivity were examined. Visceral sensitivity was assessed by recording the electromyographic (EMG) responses to graded colorectal distension (CRD) in mildly sedated rats. Responses to CRD were recorded before and after injection of FKN, minocycline or vehicle. Somatic thermal hyperalgesia was measured by latency of paw withdrawal to radiant heat. The pattern and intensity of microglial distribution at L6–S2 in the spinal cord was also compared in rats with CI and controls by fluorescence microscopy using OX-42. Results show that: (1) FKN significantly facilitated EMG responses to noxious CRD by >52% in control rats. FKN also induced thermal hyperalgesia in control rats, consistent with previous reports; (2) minocycline significantly inhibited EMG responses to noxious CRD by >70% in rats with CI compared to controls 60 min after injection. The anti-nociceptive effect of minocycline lasted for 180 min in rats with CI, reaching peak values 60 min after injection. Our results show that FKN enhances visceral and somatic nociception, whereas minocycline inhibits visceral hypersensitivity in chronically sensitized rats, which indicates a role for microglia in visceral hypersensitivity. PMID:18496611

  9. Unusual formaldehyde-induced hypersensitivity in two schoolgirls

    SciTech Connect

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

    1990-01-01

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

  10. [Drug-induced hypersensitivity syndrome and HHV-6 reactivation].

    PubMed

    Tohyama, Mikiko; Hashimoto, Koji

    2009-06-01

    Drug-induced hypersensitivity syndrome (DIHS) is an adverse reaction with clinical signs of fever, rash, and internal organ involvement. The culprit drugs of DIHS are limited to several drugs such as carbamazepine, phenytoin, phenobarbital, zonisamide, allopurinol, salazosulfapyridine, diaphenylsulphone, and mexiletine. The association of HHV-6 reactivation with DIHS has been known. Flaring of symptoms such as fever and hepatitis is closely related to HHV-6 reactivation. A combination of immunologic reaction to a drug and HHV-6 reactivation results in the severe course of DIHS.

  11. Electromagnetic hypersensitivity: The opinion of an observer neurologist

    NASA Astrophysics Data System (ADS)

    Marc-Vergnes, Jean-Pierre

    2010-11-01

    Electromagnetic hypersensitivity (EHS) is a recent, uncertain and somehow confusing concept. It is now widely agreed that people claiming to be EHS really experience symptoms. However, no evidence for a causal link between the symptoms and electromagnetic fields (EMF) has been reported. Thus, we have to wonder whether EHS constitutes truly a relevant entity. Most of the previous studies suffer from methodological flaws. Owing to the quantification of symptoms, the interdisciplinary assessment of patients, and the use of personal exposimeters, the recent studies are of better quality. A set of convergent associated signs suggests that individual neuropsychic factors take a prominent, but maybe not unique, part in this condition.

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

    PubMed

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

    2014-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  14. Alcohol and High Fat Induced Chronic Pancreatitis: TRPV4 Antagonist Reduces Hypersensitivity

    PubMed Central

    Zhang, Liping; Kline, Robert H; Deevska, Gergana; Ma, Fei; Nikolova-Karakashian, Mariana; Westlund, Karin N

    2015-01-01

    The pathogenesis of pain in chronic pancreatitis is poorly understood, and its treatment can be a major clinical challenge. Surgical and other invasive methods have variable outcomes that can be unsatisfactory. Therefore, there is a great need for further discovery of the pathogenesis of pancreatitis pain and new therapeutic targets. Human and animal studies indicate a critical role for oxidative stress and activation of transient receptor potential (TRP) cation channel subfamily members TRPV1 and TRPA1 on pancreatic nociceptors in sensitization mechanisms that result in pain. However, the in vivo role of TRPV4 in chronic pancreatitis needs further evaluation. The present study characterized a rat alcohol/high fat diet (AHF) induced chronic pancreatitis model with hypersensitivity, fibrotic pathology, and fat vacuolization consistent with the clinical syndrome. The rats with AHF induced pancreatitis develop referred visceral pain-like behaviors, i.e. decreased hindpaw mechanical thresholds and shortened abdominal and hindpaw withdrawal latency to heat. In this study, oxidative stress was characterized as well as the role of TRPV4 in chronic visceral hypersensitivity. Lipid peroxidase and oxidative stress were indicated by increased plasma thiobarbituric acid reactive substances (TBARS) and diminished pancreatic manganese superoxide dismutase (MnSOD). The secondary sensitization associated with AHF induced pancreatitis was effectively alleviated by the TRPV4 antagonist, HC 067047. Similarity of the results to those with the peripherally restricted µ-opiate receptor agonist, loperamide, suggested TRPV4 channel activated peripheral sensitization. This study using a reliable model that provides pre-clinical correlates of human chronic pancreatitis provides further evidence that TRPV4 channel is a potential therapeutic target for treatment of pancreatitis pain. PMID:26480812

  15. Hypersensitivity of Drosophila mei-41 mutants to hydroxyurea is associated with reduced mitotic chromosome stability.

    PubMed

    Banga, S S; Shenkar, R; Boyd, J B

    1986-11-01

    6 mutant alleles of the mei-41 locus in Drosophila melanogaster are shown to cause hypersensitivity to hydroxyurea in larvae. The strength of that sensitivity is directly correlated with the influence of the mutant alleles on meiosis in that: alleles exhibiting a strong meiotic effect (mei-41D2, mei-41D5, mei-41D7) are highly sensitive; alleles with negligible meiotic effects (mei-41(104)D1, mei-41(104)D2) are moderately sensitive and an allele which expresses meiotic effects only under restricted conditions (mei-41D9) has an intermediate sensitivity. This sensitivity is not a general feature of strong postreplication repair-deficient mutants, because mutants with that phenotype from other loci do not exhibit sensitivity (mus(2)205A1, mus(3)302D1, mus(3)310D1). The observed lethality is not due to hypersensitivity of DNA synthesis in mei-41 larvae to hydroxyurea as assayed by tritiated thymidine incorporation. Lethality is, however, potentially attributable to an abnormal enhancement of chromosomal aberrations by hydroxyurea in mutant mei-41 larvae. Both in vivo and in vitro exposure of neuroblast cells to hydroxyurea results in an increase in 3 types of aberrations which is several fold higher in mei-41 tissue. Since hydroxyurea disrupts DNA synthesis, these results further implicate the mei-41 locus in DNA metabolism and provide an additional tool for an elucidation of its function. The possible existence of additional genes of this nature is suggested by a more modest sensitivity to hydroxyurea which has been detected in two stocks carrying mutagen-sensitive alleles of alternate genes.

  16. TRPA1 in the spinal dorsal horn is involved in post-inflammatory visceral hypersensitivity: in vivo study using TNBS-treated rat model

    PubMed Central

    Li, Qian; Guo, Cheng-Hao; Chowdhury, Mohammed Ali; Dai, Tao-Li; Han, Wei

    2016-01-01

    Introduction The transient receptor potential ankyrin-1 (TRPA1) channel, a pain transducer and amplifier, is drawing increasing attention in the field of visceral hypersensitivity, commonly seen in irritable bowel syndrome and inflammatory bowel disease. However, the role of TRPA1 in visceral nociception during post-inflammatory states is not well defined. Here, we explore the correlation between TRPA1 expression in the spinal dorsal horn (SDH) and persistent post-inflammatory visceral hypersensitivity. Methods We injected rats intracolonically with 2,4,6-trinitrobenzene sulfonic acid (TNBS) or vehicle (n=12 per group). Post-inflammatory visceral hypersensitivity was assessed by recording the electromyographic activity of the external oblique muscle in response to colorectal distension. TRPA1 expression and distribution in the spinal cord and colon were examined by Western blotting and immunohistochemistry. Results Animals exposed to TNBS had more abdominal contractions than vehicle-injected controls (P<0.05), which corresponded to a lower nociceptive threshold. Expression of TRPA1 in the SDH (especially in the substantia gelatinosa) and the colon was significantly greater in the TNBS-treated group than in controls (P<0.05). In the SDH, the number of TRPA1-immunopositive neurons was 25.75±5.12 in the control group and 34.25±7.89 in the TNBS-treated group (P=0.023), and integrated optical density values of TRPA1 in the control and TNBS-treated groups were 14,544.63±6,525.54 and 22,532.75±7,608.11, respectively (P=0.041). Conclusion Our results indicate that upregulation of TRPA1 expression in the SDH is associated with persistent post-inflammatory visceral hypersensitivity in the rat and provides insight into potential therapeutic targets for the control of persistent visceral hypersensitivity. PMID:27980434

  17. The prevalence of dentin hypersensitivity in general dental practices in the northwest United States

    PubMed Central

    Cunha-Cruz, Joana; Wataha, John C.; Heaton, Lisa J.; Rothen, Marilynn; Sobieraj, Martin; Scott, JoAnna; Berg, Joel

    2013-01-01

    Background The prevalence of dentin hypersensitivity is uncertain, yet appropriate diagnosis and treatment of dentin hypersensitivity require accurate knowledge regarding its prevalence. The authors conducted a study to estimate the prevalence of dentin hypersensitivity in general dental practices and to investigate associated risk factors. Methods The authors conducted a cross-sectional survey of 787 adult patients from 37 general dental practices within Northwest Practice-based Research Collaborative in Evidence-based DENTistry (PRECEDENT). Dentin hypersensitivity was diagnosed by means of participants’ responses to a question regarding pain in their teeth and gingivae, and practitioner-investigators conducted a clinical examination to rule out alternative causes of pain. Participants recorded their pain level on a visual analog scale and the Seattle Scales in response to a one-second air blast. The authors used generalized estimating equation log-linear models to estimate the prevalence and the prevalence ratios. Results The prevalence of dentin hypersensitivity was 12.3 percent; patients with hypersensitivity had, on average, 3.5 hypersensitive teeth. The prevalence of dentin hypersensitivity was higher among 18- to 44-year olds than among participants 65 years or older; it also was higher in women than in men, in participants with gingival recession than in those without gingival recession and in participants who underwent at-home tooth whitening than in those who did not. Hypersensitivity was not associated with obvious occlusal trauma, noncarious cervical lesions or aggressive toothbrushing habits. Conclusions One in eight participants from general practices had dentin hypersensitivity, which was a chronic condition causing intermittent, low-level pain. Patients with hypersensitivity were more likely to be younger, to be female and to have a high prevalence of gingival recession and at-home tooth whitening. Practical Implications Given dentin

  18. Treatment of experimentally induced pneumonic pasteurellosis of young calves with tilmicosin.

    PubMed Central

    Morck, D W; Merrill, J K; Gard, M S; Olson, M E; Nation, P N

    1997-01-01

    concentrations of the antibiotic were comparatively high, even at 72 h post-infection (6.50 +/- 0.75 ppm). Lung tissue concentrations at 72 h were significantly higher in experimentally infected calves than in non-infected tilmicosin-treated animals (P < 0.05). These data demonstrate that tilmicosin was effective in treating experimentally-induced pneumonic pasteurellosis as determined by alleviation of clinical signs, pathological findings at post mortem, and presence of viable bacteria from the lung. Concentrations substantially above MIC for P. haemolytica were present in lung tissue even at 72 h following a single subcutaneous injection of 10 mg tilmicosin per kg body weight. Images Figure 2A. Figure 2B. PMID:9242998

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  1. Genetic parameters of insect bite hypersensitivity in Dutch Friesian broodmares.

    PubMed

    Schurink, A; Ducro, B J; Heuven, H C M; van Arendonk, J A M

    2011-05-01

    Insect bite hypersensitivity (IBH) is a seasonal allergic skin disease in horses caused by bites of certain Culicoides spp. The aim of our study was to investigate the maternal effect on IBH and to estimate the heritability and repeatability of IBH in the Dutch Friesian horse population. Data consisted of 3,453 Dutch Friesian broodmares with 3,763 visual observations on IBH clinical symptoms scored by 12 inspectors during organized foal inspections in 2004 and 2008. Nine percent of the mares (n = 310) were scored in both years. Mares descended from 144 sires and 2,554 dams and 26.2% of the dams (n = 669) had more than 1 offspring in the data set (range: 2 to 6). Insect bite hypersensitivity was analyzed as a binary trait with a threshold animal model with and without a maternal effect, using a Bayesian approach. Observed IBH prevalence in Dutch Friesian broodmare population was 18.2%. Heritability on the liability scale was 0.16 (SD = 0.06); heritability on the observed scale was 0.07; and repeatability was 0.89 (SD = 0.03). Maternal effect was 0.17 (SD = 0.06) and significantly differed from zero, although the animal model without a maternal effect fitted the data better. These results show that genetic and permanent environmental factors affect IBH in Dutch Friesian horses. The dam affected the IBH development of her offspring through an additive genetic influence but also by being part of their rearing environment.

  2. Hypersensitive radical probe studies of chloroperoxidase-catalyzed hydroxylation reactions.

    PubMed

    Toy, P H; Newcomb, M; Hager, L P

    1998-07-01

    The oxidation of hypersensitive radical probes by chloroperoxidase from Caldariomyces fumago (CPO) was studied in an attempt to "time" a putative radical intermediate. Oxidation of (trans-2-phenylcyclopropyl)methane, previously studied by Zaks and Dodds [Zaks, A., and Dodds, D. R. (1995) J. Am. Chem. Soc. 115, 10419-10424] was reinvestigated. Unrearranged oxidation products were found as previously reported, and control experiments demonstrated that the cyclic alcohol from oxidation at the cyclopropylcarbinyl position, while subject to further oxidation, survives CPO oxidation as detectable species. However, in contrast to the report by Zaks and Dodds, the rearranged alcohol product expected from ring opening of a cyclopropylcarbinyl radical intermediate was shown to be unstable toward the enzyme oxidation reaction. Because of this instability, two new hypersensitive radical probes, (trans-2-phenylcyclopropyl)ethane and 2-(trans-2-phenylcyclopropyl)propane, and their potential cyclic and acyclic products from oxidation at the cyclopropylcarbinyl position were synthesized and tested. Oxidation of both of these probes at the cyclopropylcarbinyl position by CPO gave unrearranged alcohol products only, but control experiments again demonstrated that the rearranged alcohol products were unstable toward CPO oxidation conditions. From the combination of the probe and control studies, the lifetime of a putative radical intermediate must be less than 3 ps. Whereas the results are consistent with an insertion mechanism for production of alcohol product, they do not exclude a very short-lived intermediate.

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

    PubMed Central

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

    2016-01-01

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

  4. Association between pollen hypersensitivity and edible vegetable allergy: a review.

    PubMed

    Caballero, T; Martín-Esteban, M

    1998-01-01

    Over the last three decades several authors have described the existence of an association between sensitivity to different pollens and sensitivity to diverse edible vegetables. An association between ragweed pollinosis and hypersensitivity to Cucurbitaceae vegetables (e.g., watermelon, melon, cucumber) and banana has been reported. Other authors have found a relationship between birch pollinosis and sensitization to hazelnut, apple, carrot, potato, kiwi and other vegetables. Additionally, several papers have shown the association between mugwort pollinosis and sensitization to celery, carrot, spices, nuts, mustard and Leguminoseae vegetables. Later, some studies showed association between grass pollinosis and sensitization to tomato, potato, green- pea, peanut, watermelon, melon, apple, orange and kiwi. Finally, an association between sensitization to plantain pollen and melon hypersensitivity was also described. The association between pollinosis and edible vegetable sensitization has been explained by the combination of different hypotheses, such as the following: 1) presence of lectins in edible vegetables; 2) existence of IgE to carbohydrates of the glycoproteins (cross-reactive carbohydrate determinants); and, 3) existence of common allergens between pollens and edible vegetables. Up to now three allergens have been identified as responsible for cross-reactivity in these associations: profilin, a 14 kd protein that regulates actin; Bet v 1, the 18 kd birch pollen allergen; and a 60-69 kd allergen. It is important to study in depth these associated sensitizations and the common allergens responsible for them in order to improve diagnostic methods and treatment of these syndromes.

  5. Airway Inflammation and Hypersensitivity Induced by Chronic Smoking

    PubMed Central

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

    2011-01-01

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

  6. Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation.

    PubMed

    Riyaz, Najeeba; Sarita, S; Arunkumar, G; Sabeena, S; Manikoth, Neeraj; Sivakumar, C P

    2012-01-01

    A 45-year-old man, on carbamazepine for the past 3 months, was referred as a case of atypical measles. On examination, he had high-grade fever, generalized itchy rash, cough, vomiting and jaundice. A provisional diagnosis of drug hypersensitivity syndrome to carbamazepine was made with a differential diagnosis of viral exanthema with systemic complications. Laboratory investigations revealed leukocytosis with eosnophilia and elevated liver enzymes. Real-time multiplex polymerase chain reaction (PCR) on throat swab and blood was suggestive of human herpesvirus-6 (HHV-6). Measles was ruled out by PCR and serology. The diagnosis of drug-induced hypersensitivity syndrome (DIHS) was confirmed, which could explain all the features manifested by the patient. HHV-6 infects almost all humans by age 2 years. It infects and replicates in CD4 T lymphocytes and establishes latency in human peripheral blood monocytes or macrophages and early bone marrow progenitors. In DIHS, allergic reaction to the causative drug stimulates T cells, which leads to reactivation of the herpesvirus genome. DIHS is treated by withdrawal of the culprit drug and administration of systemic steroids. Our patient responded well to steroids and HHV-6 was negative on repeat real-time multiplex PCR at the end of treatment.

  7. Beta-lactam hypersensitivity and cross-reactivity.

    PubMed

    Terico, Adrienne T; Gallagher, Jason C

    2014-12-01

    Penicillin is the most frequently reported cause of drug allergy, and cross-reactivity of penicillins with other beta-lactam antibiotics is an area of debate. This review evaluates the available data on immunoglobulin E-mediated penicillin hypersensitivity and cross-reactivity with cephalosporin, carbapenem, and monobactam antibiotics. A MEDLINE search was conducted from 1950 to October 2013, and selected references from review articles were also evaluated. There is a wide variety in reported incidences of cross-reactivity between penicillins and cephalosporins or carbapenems, with early retrospective studies suggesting up to 41.7% and 47.4% cross-reactivity, respectively. Conversely, the use of monobactam antibiotics is frequently employed in the case of a penicillin allergy, as prescribers believe that there is no cross-reactivity between the 2 drug classes. More recent prospective studies suggest that the rates of cross-reactivity with cephalosporins and carbapenems are <5% and <1%, respectively. Similarities in penicillin and cephalosporin side chains may play a role in cross-reactivity between these classes. Cross-reactivity with monobactams is essentially negligible; however, there are some clinical data to support an interaction between ceftazidime and aztreonam, due to the similarity of their side chains. The data reviewed suggest that avoidance of other beta-lactams in patients with type 1 hypersensitivity to penicillins should be reconsidered.

  8. Hypersensitive response of beans to Apion godmani (Coleoptera: Curculionidae).

    PubMed

    Garza, R; Vera, J; Cardona, C; Barcenas, N; Singh, S P

    2001-08-01

    High levels of resistance to Apion godinani Wagner have been reported in bean, Phaseolus vulgaris L., landraces from Mexico. We report on the role of hypersensitivity to A. godmani in five resistant and three susceptible bean genotypes. In susceptible genotypes (cultivars 'Canario 107','Jamapa', and 'Zacatecas 45'), the eggs and first instars of A. godmani were embedded in the pod mesocarp and usually were surrounded by healthy tissue. In contrast, in resistant landraces ('Amarillo 154', 'Amarillo 155', 'J-117', 'Puebla 36', and 'Pinto 168'), necrotic tissues developed concentrically around the oviposition site, encapsulating eggs and dead larvae. An inverse relationship between percentage egg and larval encapsulation at the early immature pod stages and percentage of damaged seeds at harvest was found. Results indicate that hypersensitivity in developing pods plays an important role in antibiosis to A. godmani in beans. This information will facilitate future genetic and biochemical research and provide much needed information concerning the phenotypic basis of resistance to A. godmani in bean.

  9. Esophageal sensation and esophageal hypersensitivity - overview from bench to bedside.

    PubMed

    Miwa, Hiroto; Kondo, Takashi; Oshima, Tadayuki; Fukui, Hirokazu; Tomita, Toshihiko; Watari, Jiro

    2010-10-01

    Noxious stimuli in the esophagus activate nociceptive receptors on esophageal mucosa, such as transient receptor potential, acid-sensing ion channel and the P2X family, a family of ligand-gated ion channels responsive to ATP, and this generates signals that are transmitted to the central nervous system via either spinal nerves or vagal nerves, resulting in esophageal sensation. Among the noxious stimuli, gastric acid and other gastric contents are clinically most important, causing typical reflux symptoms such as heartburn and regurgitation. A conventional acid penetration theory has been used to explain the mechanism of heartburn, but much recent evidence does not support this theory. Therefore, it may be necessary to approach the causes of heartburn symptoms from a new conceptual framework. Hypersensitivity of the esophagus, like that of other visceral organs, includes peripheral, central and probably psychosocial factor-mediated hypersensitivity, and is known to play crucial roles in the pathoegenesis of nonerosive reflux disease, functional heartburn and non-cardiac chest pain. There also are esophagitis patients who do not perceive typical symptoms. This condition is known as silent gastroesophageal reflux disease. Although the pathogenesis of silent gastroesophageal reflux disease is still not known, hyposensitivity to reflux of acid may possibly explain the condition.

  10. Pneumonitis in Syrian golden hamsters (Mesocricetus auratus) infected with Rio Mamoré virus (family Bunyaviridae, genus Hantavirus).

    PubMed

    Milazzo, Mary Louise; Eyzaguirre, Eduardo J; Fulhorst, Charles F

    2014-10-13

    Rio Mamoré virus is an etiological agent of hantavirus pulmonary syndrome in South America. The purpose of this study was to determine whether Rio Mamoré virus strain HTN-007 in Syrian golden hamsters is pathogenic. None of 37 adult hamsters infected by intramuscular injection of HTN-007, including 10 animals killed on Day 42 or 43 post-inoculation, exhibited any symptom of disease. Histological abnormalities included severe or moderately severe pneumonitis in 6 (46.2%) of the 13 animals killed on Day 7 or 10 post-inoculation. The primary target of infection in lung was the endothelium of the microvasculature. Collectively, these results indicate that Rio Mamoré virus strain HTN-007 in adult Syrian golden hamsters can cause a nonlethal disease that is pathologically similar to hantavirus pulmonary syndrome.

  11. Acute pneumonitis in a patient with adult-onset disease after toclizumab treatment with good response to anakinra.

    PubMed

    Sangüesa Gómez, Clara; Flores Robles, Bryan Josué; Jara Chinarro, Beatriz; Espinosa Malpartida, María; Barbadillo Mateos, Carmen

    Pulmonary involvement in the form of acute pneumonitis in adult-onset Still's disease (AOSD) is an uncommon manifestation, with few cases reported in the literature. We report the case of a 61-year-old male with 3 years of AOSD evolution, treated with methotrexate (MTX) and half-dose corticosteroids, which debuted with symptoms of fever, dyspnea and dry cough after 3 weeks of receiving the first dose of tocilizumab (TCZ). In the follow-up study showed leukocytosis with left shift, elevated serum ferritin and C-reactive protein standard. The chest CT scan showed ground-glass pattern predominantly in central and upper lobes and the BAL shows an increase in the percentage of lymphocyte with normal subpopulations and negative cultures. MTX and TCM were suspended, prednisone was increased to 30mg/day and within a week Anakinra 100mg/day SC was iniciated, noting in a few days a progressive clinical, analytical and radiological improvement.

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

    PubMed Central

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

    2012-01-01

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

  13. Identification of MHC Haplotypes Associated with Drug-induced Hypersensitivity Reactions in Cynomolgus Monkeys.

    PubMed

    Wu, Hong; Whritenour, Jessica; Sanford, Jonathan C; Houle, Christopher; Adkins, Karissa K

    2017-01-01

    Drug-induced hypersensitivity reactions can significantly impact drug development and use. Studies to understand risk factors for drug-induced hypersensitivity reactions have identified genetic association with specific human leukocyte antigen (HLA) alleles. Interestingly, drug-induced hypersensitivity reactions can occur in nonhuman primates; however, association between drug-induced hypersensitivity reactions and major histocompatibility complex (MHC) alleles has not been described. In this study, tissue samples were collected from 62 cynomolgus monkeys from preclinical studies in which 9 animals had evidence of drug-induced hypersensitivity reactions. Microsatellite analysis was used to determine MHC haplotypes for each animal. A total of 7 haplotypes and recombinant MHC haplotypes were observed, with distribution frequency comparable to known MHC I allele frequency in cynomolgus monkeys. Genetic association analysis identified alleles from the M3 haplotype of the MHC I B region (B*011:01, B*075:01, B*079:01, B*070:02, B*098:05, and B*165:01) to be significantly associated (χ(2) test for trend, p < 0.05) with occurrence of drug-induced hypersensitivity reactions. Sequence similarity from alignment of alleles in the M3 haplotype B region and HLA alleles associated with drug-induced hypersensitivity reactions in humans was 86% to 93%. These data demonstrate that MHC alleles in cynomolgus monkeys are associated with drug-induced hypersensitivity reactions, similar to HLA alleles in humans.

  14. Clinical importance of carbapenem hypersensitivity in patients with self-reported and documented penicillin allergy.

    PubMed

    Prescott, William A; Kusmierski, Kristen A

    2007-01-01

    The risk of carbapenem hypersensitivity in patients with self-reported or documented penicillin allergy needs to be determined so that practitioners can make better-informed decisions regarding antibiotic therapy for this patient population. The risk of cross-reactivity between penicillin and carbapenem antibiotics initially was reported to approach 50%. Recent retrospective studies have suggested that the clinical risk of cross-hypersensitivity between these two drug classes is 9.2-11%, which is significantly lower than initially reported. Patients whose history of penicillin allergy is self-reported and is not type 1 may be at moderate risk for hypersensitivity when treated with a carbapenem antibiotic. The risk of hypersensitivity appears to be higher in patients whose penicillin allergy was documented by a health care provider, those with several antibiotic allergies, and those with a positive penicillin skin test result or a history of type 1 penicillin hypersensitivity.

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

    PubMed Central

    Sabir, Mohammad

    2015-01-01

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

  16. Suppression of spinal connexin 43 expression attenuates mechanical hypersensitivity in rats after an L5 spinal nerve injury.

    PubMed

    Xu, Qian; Cheong, Yong-Kwan; He, Shao-Qiu; Tiwari, Vinod; Liu, Jian; Wang, Yun; Raja, Srinivasa N; Li, Jinheng; Guan, Yun; Li, Weiyan

    2014-04-30

    Activation of spinal astrocytes may contribute to neuropathic pain. Adjacent astrocytes can make direct communication through gap junctions formed by connexin 43 (Cx43) in the central nervous system. Yet, the role of spinal astroglial gap junctions in neuropathic pain is not fully understood. Since Cx43 is the connexin isoform expressed preferentially in astrocytes in the spinal cord, we used a small interfering RNA (siRNA) approach to examine whether suppression of spinal Cx43 expression inhibits mechanical hypersensitivity in rats after an L5 spinal nerve ligation (SNL). SNL rats were administered intrathecal Cx43 siRNA (3μg/15μl, twice/day) or an equal amount of mismatch siRNA (control) on days 14-17 post-SNL. Cx43 siRNA, but not mismatch siRNA, alleviated mechanical hypersensitivity in SNL rats. Furthermore, Western blot analysis showed that the pain inhibition induced by Cx43 siRNA correlated with downregulation of Cx43 expression, but not that of Cx36 (the neuronal gap junction protein) or glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes) in the spinal cord of SNL rats. Western blot analysis and immunohistochemistry also showed that SNL increased GFAP expression, but decreased Cx43 expression, in spinal cord. Our results provide direct evidence that selective suppression of spinal Cx43 after nerve injury alleviates neuropathic mechanical hypersensitivity. These findings suggest that in the spinal cord, the enhanced function of astroglial gap junctions, especially those formed by Cx43, may be important to neuropathic pain in SNL rats.

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  18. Acute symptoms of drug hypersensitivity (urticaria, angioedema, anaphylaxis, anaphylactic shock).

    PubMed

    Limsuwan, Ticha; Demoly, Pascal

    2010-07-01

    Drug hypersensitivity reactions (HSRs) are the adverse effects of drugs which, when taken at doses generally tolerated by normal subjects, clinically resemble allergy. Immediate-reaction of drug HSRs are those that occur less than 1 hour after the last drug intake, usually in the form of urticaria, angioedema, rhinitis, conjunctivitis, bronchospasm, and anaphylaxis or anaphylactic shock. Acute urticarial and angioedema reactions are common clinical problems frequently encountered by internists and general practitioners. They are not specific to drug allergic reaction, and can be caused by various pathogenic mechanisms. Despite the benign course of urticaria and angioedema, a mucocutaneous swelling of the upper respiratory tract could be life-threatening by itself or a feature of anaphylaxis. This article reviews acute symptoms of drug HSR-related urticaria, angioedema, anaphylaxis, and anaphylactic shock, and how clinicians should approach these problems.

  19. Antiepileptic hypersensitivity syndrome: clinicians beware and be aware.

    PubMed

    Bessmertny, Olga; Pham, Trinh

    2002-01-01

    Antiepileptic hypersensitivity syndrome is a serious idiosyncratic, non-dose-related adverse reaction reported to occur with phenytoin, phenobarbital, carbamazepine, primidone, and lamotrigine. The reaction usually develops 1 to 12 weeks after initiation of therapy with one of the above agents and is recognized by the classic triad of fever, rash, and internal organ involvement. Immediate discontinuation of the suspected anticonvulsant is essential for good outcome. Patients usually are managed supportively with hydration, antihistamines, H(2)-receptor blockers, and topical corticosteroids. In severe cases, the use of systemic corticosteroids may be necessary. The use of intravenous immune globulin should be limited to severe cases where Kawasaki disease or idiopathic thrombocytopenic purpura cannot be ruled out. Education of health care professionals and patients is imperative to improving outcomes and prevention of this reaction in the future.

  20. Mast Cells in Lung Homeostasis: Beyond Type I Hypersensitivity.

    PubMed

    Campillo-Navarro, Marcia; Chávez-Blanco, Alma D; Wong-Baeza, Isabel; Serafín-López, Jeanet; Flores-Mejía, Raúl; Estrada-Parra, Sergio; Estrada-García, Iris; Chacón-Salinas, Rommel

    2014-06-01

    Lungs are indispensable organs for the respiratory process, and maintaining their homeostasis is essential for human health and survival. However, during the lifetime of an individual, the lungs suffer countless insults that put at risk their delicate organization and function. Many cells of the immune system participate to maintain this equilibrium and to keep functional lungs. Among these cells, mast cells have recently attracted attention because of their ability to rapidly secrete many chemical and biological mediators that modulate different processes like inflammation, angiogenesis, cell proliferation, etc. In this review, we focus on recent advances in the understanding of the role that mast cells play in lung protection during infections, and of the relation of mast cell responses to type I hypersensitivity-associated pathologies. Furthermore, we discuss the potential role of mast cells during wound healing in the lung and its association with lung cancer, and how mast cells could be exploited as therapeutic targets in some diseases.

  1. THE MECHANISM OF ACTION OF CORTISONE IN EXPERIMENTAL HYPERSENSITIVITY

    PubMed Central

    Germuth, Frederick G.

    1953-01-01

    Cortisone markedly suppressed the cardiovascular and renal lesions of serum sickness type hypersensitivity which ordinarily develop following the intravenous injection of bovine albumin. The inhibitory effect of cortisone on the allergic granulomatous lesions of the spleen was less striking; the lesions were less extensive, but the percentage of animals affected was unchanged. Cortisone in the dosage employed had no effect on the elimination of antigen following its intravenous administration or on the appearance of circulating antibody. These findings indicate that inhibition of the lesions of serum sickness by cortisone does not depend on the suppression of antibody production. Therefore, it is inferred that cortisone somehow protects the animal from the damaging effects of antigen-antibody union. PMID:13069645

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

    PubMed

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

    1999-03-01

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

  3. Persistent Skin Reactions and Aluminium Hypersensitivity Induced by Childhood Vaccines.

    PubMed

    Salik, Elaha; Løvik, Ida; Andersen, Klaus E; Bygum, Anette

    2016-11-02

    There is increasing awareness of reactions to vaccination that include persistent skin reactions. We present here a retrospective investigation of long-lasting skin reactions and aluminium hypersensitivity in children, based on medical records and questionnaires sent to the parents. In the 10-year period 2003 to 2013 we identified 47 children with persistent skin reactions caused by childhood vaccinations. Most patients had a typical presentation of persisting pruritic subcutaneous nodules. Five children had a complex diagnostic process involving paediatricians, orthopaedics and plastic surgeons. Two patients had skin biopsies performed from their skin lesions, and 2 patients had the nodules surgically removed. Forty-two children had a patch-test performed with 2% aluminium chloride hexahydrate in petrolatum and 39 of them (92%) had a positive reaction. The persistent skin reactions were treated with potent topical corticosteroids and disappeared slowly. Although we advised families to continue vaccination of their children, one-third of parents omitted or postponed further vaccinations.

  4. Drug-induced hypersensitivity syndrome due to carbapenem antibiotics.

    PubMed

    Goto, Mizuki; Shimizu, Fumiaki; Takeo, Naoko; Okamoto, Osamu; Katagiri, Kazumoto; Ikewaki, Junji; Ogata, Masao; Kadota, Jun-ichi; Fujiwara, Sakuhei

    2010-04-01

    Drug-induced hypersensitivity syndrome (DIHS) is characterized by a serious adverse systemic reaction that usually appears after a 3-6-week exposure to certain drugs, for example, anticonvulsants. Many different precipitating factors have been reported, but the pathophysiology of DIHS remains unknown. However, reactivation of members of the human herpesvirus (HHV) family, and of HHV-6 in particular, has been reported in patients with DIHS. We report the case of a 64-year-old man who developed a generalized erythematous rash, fever, hepatic failure, lymphadenopathy and an increased number of atypical lymphocytes. In addition, reactivation of HHV-6 and cytomegalovirus (CMV) was demonstrated by real-time quantitative amplification by polymerase chain reaction. The patient was given a diagnosis of DIHS due to carbapenem antibiotics based on his clinical course, laboratory data, and results of lymphocyte-stimulation tests with various drugs. This is the first report, to our knowledge, of DIHS induced by carbapenem antibiotics.

  5. Topical capsaicin application causes cold hypersensitivity in awake monkeys.

    PubMed

    Kamo, Hiroshi; Honda, Kuniya; Kitagawa, Junichi; Tsuboi, Yoshiyuki; Kondo, Masahiro; Taira, Masato; Yamashita, Akiko; Katsuyama, Narumi; Masuda, Yuji; Kato, Takafumi; Iwata, Koichi

    2008-06-01

    Recent animal studies have demonstrated that many trigeminal ganglion neurons co-express TRPV1 and TRPA1 receptors following peripheral inflammation. In the present study, we examined whether cold receptors were sensitized by capsaicin in awake monkeys. Two monkeys were trained to detect a change in cold stimulus temperature (30 degrees C to 0.5, 1.0, 1.5 or 2.0 degrees C) applied to the facial skin. A total of 589 trials were studied, and the number of escape and hold-through trials and detection latency were measured. The number of escape trials was increased after capsaicin treatment, whereas that of hold-through trials was decreased. Detection latency was significantly decreased after capsaicin treatment. The present findings suggest that topical application of capsaicin to the facial skin induces reversible hypersensitivity to a facial cold stimulus in behaving monkeys.

  6. Gastroenterology case report of mesalazine-induced cardiopulmonary hypersensitivity.

    PubMed

    Ferrusquía, José; Pérez-Martínez, Isabel; Gómez de la Torre, Ricardo; Fernández-Almira, María Luisa; de Francisco, Ruth; Rodrigo, Luis; Riestra, Sabino

    2015-04-07

    Mesalazine is a 5-aminosalicylic acid derivative that has been widely used to treat patients with inflammatory bowel disease. Accumulating evidence indicates that mesalazine has a very low rate of adverse drug reactions and is well tolerated by patients. However, a few cases of pulmonary and cardiac disease related to mesalazine have been reported in the past, though infrequently, preventing clinicians from diagnosing the conditions early. We describe the case of a 32-year-old man with ulcerative colitis who was admitted with a two-month history of persistent fever following mesalazine treatment initiated 14 mo earlier. At the time of admission, mesalazine dose was increased from 1.5 to 3.0 g/d, and antibiotic therapy was started with no improvement. Three weeks after admission, the patient developed dyspnea, non-productive cough, and chest pain. Severe eosinophilia was detected in laboratory tests, and a computed tomography scan revealed interstitial infiltrates in both lungs, as well as a large pericardial effusion. The bronchoalveolar lavage reported a CD4/CD8 ratio of 0.5, and an increased eosinophil count. Transbronchial biopsy examination showed a severe eosinophilic infiltrate of the lung tissue. Mesalazine-induced cardiopulmonary hypersensitivity was suspected after excluding other possible etiologies. Consequently, mesalazine treatment was suspended, and corticosteroid therapy was initiated, resulting in resolution of symptoms and radiologic abnormalities. We conclude that mesalazine-induced pulmonary and cardiac hypersensitivity should always be considered in the differential diagnosis of unexplained cardiopulmonary symptoms and radiographic abnormalities in patients with inflammatory bowel disease.

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

    PubMed

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

    2009-09-01

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

  8. Gastroenterology case report of mesalazine-induced cardiopulmonary hypersensitivity

    PubMed Central

    Ferrusquía, José; Pérez-Martínez, Isabel; Gómez de la Torre, Ricardo; Fernández-Almira, María Luisa; de Francisco, Ruth; Rodrigo, Luis; Riestra, Sabino

    2015-01-01

    Mesalazine is a 5-aminosalicylic acid derivative that has been widely used to treat patients with inflammatory bowel disease. Accumulating evidence indicates that mesalazine has a very low rate of adverse drug reactions and is well tolerated by patients. However, a few cases of pulmonary and cardiac disease related to mesalazine have been reported in the past, though infrequently, preventing clinicians from diagnosing the conditions early. We describe the case of a 32-year-old man with ulcerative colitis who was admitted with a two-month history of persistent fever following mesalazine treatment initiated 14 mo earlier. At the time of admission, mesalazine dose was increased from 1.5 to 3.0 g/d, and antibiotic therapy was started with no improvement. Three weeks after admission, the patient developed dyspnea, non-productive cough, and chest pain. Severe eosinophilia was detected in laboratory tests, and a computed tomography scan revealed interstitial infiltrates in both lungs, as well as a large pericardial effusion. The bronchoalveolar lavage reported a CD4/CD8 ratio of 0.5, and an increased eosinophil count. Transbronchial biopsy examination showed a severe eosinophilic infiltrate of the lung tissue. Mesalazine-induced cardiopulmonary hypersensitivity was suspected after excluding other possible etiologies. Consequently, mesalazine treatment was suspended, and corticosteroid therapy was initiated, resulting in resolution of symptoms and radiologic abnormalities. We conclude that mesalazine-induced pulmonary and cardiac hypersensitivity should always be considered in the differential diagnosis of unexplained cardiopulmonary symptoms and radiographic abnormalities in patients with inflammatory bowel disease. PMID:25852295

  9. Genetic parameters of insect bite hypersensitivity in the Old Grey Kladruber horse.

    PubMed

    Citek, J; Vostry, L; Vostra-Vydrova, H; Brzakova, M; Prantlova, V

    2017-01-01

    The objective of this study was to assess the genetic parameters of insect bite hypersensitivity (IBH) in the Old Grey Kladruber horse, an original Czech warmblood horse breed. Insect bite hypersensitivity is a recurrent allergic skin disease affecting horses worldwide. Its etiology is multifactorial. The defect is genetically controlled, and the starting impulse is a bite by midges of the spp. and less frequently spp. Knowledge about the associated genes is limited. Horses were kept by the National Stud in Kladruby (1,146 measurements) and by 10 private breeders (63 measurements). The horses were visually scored by the same inspector over a period of 13 yr from 1996 to 2009. A linear logistic model with a binary variable was used for subsequent statistical analysis. The fixed effects of the farm, year of evaluation, age of evaluation, and sex were significant, and the nonsignificant effect was the intensity of greying. The animals from the National Stud were more strongly affected by IBH than animals from private studs. The National Stud is located near the Labe River, at an altitude of 206 m; there are bottomland pastures in the vicinity, blind river arms, and numerous pools and marshes, and the climate is mild. These conditions are convenient for horse keeping but also for the propagation of . The stallions were less affected than the mares. The occurrence in years of age was influenced by selection; scoring began in the first year of age, and when the young animal was repeatedly positive, it was eliminated from breeding. The estimated h differed significantly from 0, and the direct h were 0.626 in the animal model with a maternal effect, 0.359 in the animal model without a maternal effect, and 0.363 in the animal model without correlation between direct and maternal effect. The maternal h was 0.305. The estimated repeatabilities were 0.636 with a maternal effect, 0.615 without a maternal effect, and 0.623 without correlation. The h of IBH was found to be medium

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    SciTech Connect

    Liu Fan; Yorke, Ellen D.; Belderbos, Jose S.A.; Borst, Gerben R.; Rosenzweig, Kenneth E.; Lebesque, Joos V.; Jackson, Andrew

    2013-01-01

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

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

    SciTech Connect

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

    2011-07-01

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

  14. Host transcriptomic responses to pneumonic plague reveal that Yersinia pestis inhibits both the initial adaptive and innate immune responses in mice.

    PubMed

    Yang, Huiying; Wang, Tong; Tian, Guang; Zhang, Qingwen; Wu, Xiaohong; Xin, Youqian; Yan, Yanfeng; Tan, Yafang; Cao, Shiyang; Liu, Wanbing; Cui, Yujun; Yang, Ruifu; Du, Zongmin

    2017-01-01

    Pneumonic plague is the most deadly form of infection caused by Yersinia pestis and can progress extremely fast. However, our understanding on the host transcriptomic response to pneumonic plague is insufficient. Here, we used RNA-sequencing technology to analyze transcriptomic responses in mice infected with fully virulent strain 201 or EV76, a live attenuated vaccine strain lacking the pigmentation locus. Approximately 600 differentially expressed genes (DEGs) were detected in lungs from both 201- and EV76-infected mice at 12h post-infection (hpi). DEGs in lungs of 201-infected mice exceeded 2000 at 48hpi, accompanied by sustained large numbers of DEGs in the liver and spleen; however, limited numbers of DEGs were detected in those organs of EV-infected mice. Remarkably, DEGs in lungs were significantly enriched in critical immune responses pathways in EV76-infected but not 201-infected mice, including antigen processing and presentation, T cell receptor signaling among others. Pathological and bacterial load analyses confirmed the rapid systemic dissemination of 201-infection and the confined EV76-infection in lungs. Our results suggest that fully virulent Y. pestis inhibits both the innate and adaptive immune responses that are substantially stimulated in a self-limited infection, which update our holistic views on the transcriptomic response to pneumonic plague.

  15. New Insights into Autoinducer-2 Signaling as a Virulence Regulator in a Mouse Model of Pneumonic Plague

    PubMed Central

    Fitts, Eric C.; Andersson, Jourdan A.; Kirtley, Michelle L.; Sha, Jian; Erova, Tatiana E.; Chauhan, Sadhana; Motin, Vladimir L.

    2016-01-01

    ABSTRACT The Enterobacteriaceae family members, including the infamous Yersinia pestis, the causative agent of plague, have a highly conserved interbacterial signaling system that is mediated by the autoinducer-2 (AI-2) quorum-sensing molecule. The AI-2 system is implicated in regulating various bacterial virulence genes in diverse environmental niches. Deletion of the gene encoding the synthetic enzyme for the AI-2 substrate, luxS, leads to either no significant change or, paradoxically, an increase in in vivo bacterial virulence. We showed that deletion of the rbsA and lsrA genes, components of ABC transport systems that interact with AI-2, synergistically disrupted AI-2 signaling patterns and resulted in a more-than-50-fold decrease in Y. pestis strain CO92 virulence in a stringent pneumonic plague mouse model. Deletion of luxS or lsrK (encoding AI-2 kinase) from the ΔrbsA ΔlsrA background strain or complementation of the ΔrbsA ΔlsrA mutant with the corresponding gene(s) reverted the virulence phenotype to that of the wild-type Y. pestis CO92. Furthermore, the administration of synthetic AI-2 in mice infected with the ΔrbsA ΔlsrA ΔluxS mutant strain attenuated this triple mutant to a virulence phenotype similar to that of the ΔrbsA ΔlsrA strain in a pneumonic plague model. Conversely, the administration of AI-2 to mice infected with the ΔrbsA ΔlsrA ΔluxS ΔlsrK mutant did not rescue animals from lethality, indicating the importance of the AI-2–LsrK axis in regulating bacterial virulence. By performing high-throughput RNA sequencing, the potential role of some AI-2-signaling-regulated genes that modulated bacterial virulence was determined. We anticipate that the characterization of AI-2 signaling in Y. pestis will lead to reexamination of AI-2 systems in other pathogens and that AI-2 signaling may represent a broad-spectrum therapeutic target to combat antibiotic-resistant bacteria, which represent a global crisis of the 21st century. IMPORTANCE

  16. Further characterization of a rat model of varicella zoster virus-associated pain: Relationship between mechanical hypersensitivity and anxiety-related behavior, and the influence of analgesic drugs.

    PubMed

    Hasnie, F S; Breuer, J; Parker, S; Wallace, V; Blackbeard, J; Lever, I; Kinchington, P R; Dickenson, A H; Pheby, T; Rice, A S C

    2007-02-23

    Persistent herpes zoster-associated pain is a significant clinical problem and an area of largely unmet therapeutic need. Progress in elucidating the underlying pathophysiology of zoster-associated pain and related co-morbidity behavior, in addition to appropriately targeted drug development has been hindered by the lack of an appropriate animal model. This study further characterizes a recently developed rat model of zoster-associated hypersensitivity and investigates (a) response to different viral strains; (b) relationship between viral inoculum concentration ('dose') and mechanical hypersensitivity ('response'); (c) attenuation of virus-associated mechanical hypersensitivity by clinically useful analgesic drugs; and (d) measurement of pain co-morbidity (anxiety-like behavior) and pharmacological intervention in the open field paradigm (in parallel with models of traumatic peripheral nerve injury). Varicella zoster virus was propagated on fibroblast cells before s.c. injection into the glabrous footpad of the left hind limb of adult male Wistar rats. Control animals received injection of uninfected fibroblast cells. Hind-limb reflex withdrawal thresholds to mechanical, noxious thermal and cooling stimuli were recorded at specified intervals post-infection. Infection with all viral strains was associated with a dose-dependent mechanical hypersensitivity but not a thermal or cool hypersensitivity. Systemic treatment with i.p. morphine (2.5 mg/kg), amitriptyline (10 mg/kg), gabapentin (30 mg/kg), (S)-(+)-ibuprofen (20 mg/kg) and the cannabinoid WIN55,212-2 (2 mg/kg) but not the antiviral, acyclovir (50 mg/kg), was associated with a reversal of mechanical paw withdrawal thresholds. In the open field paradigm, virus-infected and nerve-injured animals demonstrated an anxiety-like pattern of ambulation (reduced entry into the central area of the open arena) which was positively correlated with mechanical hypersensitivity. This may reflect pain-related co

  17. Recovery from sexual exhaustion-induced copulatory inhibition and drug hypersensitivity follow a same time course: two expressions of a same process?

    PubMed

    Rodríguez-Manzo, Gabriela; Guadarrama-Bazante, Irma Lorena; Morales-Calderón, Aída

    2011-03-01

    Male rats allowed copulating without restriction with a single oestrous female ejaculate repeatedly until reaching sexual exhaustion. Twenty-four hours after this process, sexually exhausted males exhibit a series of physiological alterations when compared to non-exhausted males. Among them, the most conspicuous are a long-lasting sexual behaviour inhibition and a generalised hypersensitivity to drug actions. The objective of the present work was to establish if there was a correlation between these two features of sexual satiation in relation to the duration of its expression. To that aim, we characterised the spontaneous sexual behaviour recovery process from sexual satiation, as well as the duration of the drug hypersensitivity phenomenon. The latter was assessed through the appearance of a sign of the serotonergic syndrome: the flat body posture. Results showed that the drug hypersensitivity phenomenon and the sexual inhibition that results from copulation to satiation follow a similar time course of recovery, with a drastic decrease in their expression 96 h after the sexual satiation process. This finding indicates that these phenomena might represent two expressions of a same brain plasticity process, as suggested by the long lasting character of both events, which interestingly appears to be reversible.

  18. The predictive role of delayed cutaneous hypersensitivity testing in postoperative complications.

    PubMed

    Schackert, H K; Betzler, M; Zimmermann, G F; Decker, R; Geelhaar, G H; Edler, L; Hess, C; Herfarth, C

    1986-06-01

    Ten parameters, including delayed cutaneous hypersensitivity testing (DCH), were evaluated with regard to their predictive value in instances of postoperative septic complications. In 302 patients undergoing surgical treatment, 45 complications, including wound infection, abscess, pneumonia and sepsis, were seen postoperatively in 42 patients. When these patients were compared with 260 patients without complications, hemoglobin, leukocyte count, serum albumin, total protein, blood sedimentation rate, age and sex were found not to contribute to the prediction of postoperative complications. In DCH testing, the complication rate increased from 7.5 per cent in normergic patients to 20.6 per cent in anergic patients. With increasing length and severity of operation, the complication rate increased from 6.5 to 26.4 per cent and from 6.5 to 31.8 per cent, respectively. Only in severe, long lasting operations could DCH testing differentiate the complication risk. Normergic patients had a 8.6 per cent complication rate; hypoergic patients, 36.6 per cent, and anergic patients, 37.5 per cent. The results of DCH testing did not correlate with the complication rate in any of the other operative groups. In conclusion, the predictive value of DCH testing is clearly greater in groups of patients highly affected by the operative trauma. The results of this study show that it is important to consider both host defense mechanisms and environmental factors in the assessment of operative risks.

  19. [Delayed hypersensitivity after anthrax vaccination. I--Study of guinea pigs vaccinated against anthrax].

    PubMed

    Shlyakhov, E; Rubinstein, E

    1994-01-01

    To evaluate delayed hypersensitivity after anthrax vaccination, an Anthraxin skin test was performed in 682 guinea pigs at various times after immunization with veterinary unencapsulated active anthrax vaccine. Results were compared with those obtained in unimmunized control guinea pigs (n = 216), in guinea pigs that received a non-immunizing dose of live vaccine (n = 183) and in guinea pigs inoculated with inactivated vaccine (n = 120). Anthraxin skin tests were positive in the first postvaccination days. The incidence and intensity of positive tests peaked between two weeks and one month after vaccination and then gradually decreased during the first year. Study of resistance of guinea pigs to an inoculum at a lethal dose of a virulent strain of Bacillus anthracis showed a close correlation between positive tests and resistance. These findings demonstrate development of cell-mediated immunity after anthrax vaccination. The Anthraxin skin test should have practical applications for the production of vaccines and for evaluation of the immune status of vaccinated livestock [corrected].

  20. The phytoalexin resveratrol regulates the initiation of hypersensitive cell death in Vitis cell.

    PubMed

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

    2011-01-01

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

  1. THE USE OF SPECIFIC "LYMPHOCYTE" ANTISERA TO INHIBIT HYPERSENSITIVE REACTIONS OF THE "DELAYED" TYPE

    PubMed Central

    Waksman, Byron H.; Arbouys, Simone; Arnason, Barry G.

    1961-01-01

    Rabbit antisera against normal guinea pig lymph node, when injected into guinea pigs, produced transient depression of the level of blood lymphocytes. It had no effect on other circulating cellular elements. Repeated injection over several days produced lymphopenia, which became progressively less marked with continued treatment, and clear-cut depletion of small lymphocytes in lymph nodes, whether draining an inoculation site or remote. In guinea pigs treated with lymphocyte antiserum, there was marked suppression of the tuberculin and contact allergic reactions and the "delayed" skin reaction to purified diphtheria toxoid, and a relative suppression of allergic encephalomyelitis and the rejection of first set skin homografts. There was a slight effect on second set graft rejection and no effect on PCA or the reversed passive Arthus reaction. Non-specific reactions to intradermal turpentine or to concentrated dinitrochlorobenzene placed on the skin were moderately reduced. The suppression of these reactions (except allergic encephalomyelitis) was closely correlated with the degree of lymphopenia. Lymphocyte antiserum absorbed with normal blood white cells lost both its lymphopenic effect and its ability to suppress the tuberculin reaction. It is tentatively concluded that a circulating mononuclear cell, probably the small lymphocyte, is the primary reactant in the various types of delayed hypersensitive reactions. PMID:14004486

  2. Bacteriophage Mu as a genetic tool to study Erwinia amylovora pathogenicity and hypersensitive reaction on tobacco.

    PubMed Central

    Vanneste, J L; Paulin, J P; Expert, D

    1990-01-01

    Erwinia amylovora 1430 was shown to be sensitive to Mu G(-) particles. Infection resulted either in lytic development or in lysogenic derivatives with insertion of the Mu genome at many sites in the bacterial chromosome. We used the Mu d1Bx::Tn9 (lac Apr Cmr) derivative, called Mu dX, to identify mutants affected in pathogenicity and in their ability to induce a hypersensitive reaction (HR) on tobacco plants. Inoculation of 1,400 lysogenic derivatives on apple root calli led to the identification of 12 mutants in three classes: (i) class 1 mutants were nonpathogenic and unable to induce an HR on tobacco plants; (ii) class 2 mutants were nonpathogenic but retained the ability to induce an HR; and (iii) class 3 mutants showed attenuated virulence. Of the 12 mutants, 8 had a single insertion of the Mu dX prophage. For class 1 and 2 mutants, reversion to pathogenicity was concomitant with the loss of the Mu dX prophage. Furthermore, revertants from the class 1 mutants also recovered the ability to induce an HR on tobacco plants. Five of the six class 3 mutants were impaired in exopolysaccharide production. No changes of the envelope structure (lipopolysaccharide and outer membrane proteins) were correlated with differences in pathogenicity. One class 3 mutant did not produce any functional siderophore, suggesting that iron uptake could be involved in pathogenicity. Images FIG. 2 FIG. 3 FIG. 4 FIG. 5 PMID:2137121

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    1995-04-01

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

  5. Host Genotype and Hypersensitive Reaction Influence Population Levels of Xanthomonas campestris pv. vitians in Lettuce.

    PubMed

    Bull, Carolee T; Gebben, Samantha J; Goldman, Polly H; Trent, Mark; Hayes, Ryan J

    2015-03-01

    Dynamics of population sizes of Xanthomonas campestris pv. vitians inoculated onto or into lettuce leaves were monitored on susceptible and resistant cultivars. In general, population growth was greater for susceptible (Clemente, Salinas 88, Vista Verde) than resistant (Batavia Reine des Glaces, Iceberg, Little Gem) cultivars. When spray-inoculated or infiltrated, population levels of X. campestris pv. vitians were consistently significantly lower on Little Gem than on susceptible cultivars, while differences in the other resistant cultivars were not consistently statistically significant. Populations increased at an intermediate rate on cultivars Iceberg and Batavia Reine des Glaces. There were significant positive correlations between bacterial concentration applied and disease severity for all cultivars, but bacterial titer had a significantly greater influence on disease severity in the susceptible cultivars than in Little Gem and an intermediate influence in Iceberg and Batavia Reine des Glaces. Infiltration of X. campestris pv. vitians strains into leaves of Little Gem resulted in an incompatible reaction, whereas compatible reactions were observed in all other cultivars. It appears that the differences in the relationship between population dynamics for Little Gem and the other cultivars tested were due to the hypersensitive response in cultivar Little Gem. These findings have implications for disease management and lettuce breeding because X. campestris pv. vitians interacts differently with cultivars that differ for resistance mechanisms.

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

    PubMed Central

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

    1977-01-01

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

  7. Impact of clinical and subclinical hypersensitivity to asparaginase in acute lymphoblastic leukemia.

    PubMed

    Asselin, Barbara L; Fisher, Vicki

    2014-12-01

    Asparaginase is an essential element of acute lymphoblastic leukemia treatment. It depletes serum asparagine (an amino acid necessary for synthesis of cellular proteins), deprives leukemic blast cells of asparagine, and eventually results in cell death. To gain benefit from asparaginase, asparagine depletion must be ensured by giving intensive therapy and completing the full course of treatment. Three formulations of asparaginase exist; two are derived from Escherichia coli, a native form and pegylated form, and one is derived from Erwinia chrysanthemi (Erwinia asparaginase). Like many large proteins, asparaginases are immunogenic, and some patients develop antibodies to asparaginase. Antibodies may result in clinical hypersensitivity or subclinical hypersensitivity without symptoms, and both can result in a reduction in asparaginase activity and may affect therapeutic benefit. Clinical hypersensitivity is the most common reason for patients to stop asparaginase treatment. Subclinical hypersensitivity can only be identified by laboratory testing; therapeutic monitoring of asparaginase activity is used as a surrogate measure for asparagine depletion.

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

    PubMed

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

    1998-05-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Lucker, Jay R.; Doman, Alex

    2015-01-01

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

  11. Low-Dose Tricyclics for Esophageal Hypersensitivity: Is it all Placebo Effect?

    PubMed

    Keefer, Laurie; Kahrilas, Peter J

    2016-02-01

    Limsrivilai et al. report on a randomized control trial (RCT) testing the efficacy of imipramine for treating esophageal hypersensitivity and functional heartburn, the first RCT to test this therapy in this indication. Among 43 functional heartburn and esophageal hypersensitivity patients randomized to treatment with 25 mg qhs imipramine and 40 randomized to matched placebo, the response rates, judged by a 50% reduction in gastroesophageal reflux disease symptoms, were 37.2% and 37.5%, respectively, with no observed difference between patients with hypersensitivity and those with functional heartburn. On the positive side, imipramine treatment was associated with improvement in quality of life as assessed by total SF-36 score. Although negative at first glance, there are several important lessons from this study: (i) low-dose tricyclic is sufficient in these patients; (ii) proton pump inhibitors can (and should) be discontinued when they are ineffective; and (iii) distinguishing between functional heartburn and esophageal hypersensitivity is of unclear clinical relevance.

  12. 915 MHz microwaves and 50 Hz magnetic field affect chromatin conformation and 53BP1 foci in human lymphocytes from hypersensitive and healthy persons.

    PubMed

    Belyaev, Igor Y; Hillert, Lena; Protopopova, Marina; Tamm, Christoffer; Malmgren, Lars O G; Persson, Bertil R R; Selivanova, Galina; Harms-Ringdahl, Mats

    2005-04-01

    We used exposure to microwaves from a global system for mobile communication (GSM) mobile phone (915 MHz, specific absorption rate (SAR) 37 mW/kg) and power frequency magnetic field (50 Hz, 15 muT peak value) to investigate the response of lymphocytes from healthy subjects and from persons reporting hypersensitivity to electromagnetic field (EMF). The hypersensitive and healthy donors were matched by gender and age and the data were analyzed blind to treatment condition. The changes in chromatin conformation were measured with the method of anomalous viscosity time dependencies (AVTD). 53BP1 protein, which has been shown to colocalize in foci with DNA double strand breaks (DSBs), was analyzed by immunostaining in situ. Exposure at room temperature to either 915 MHz or 50 Hz resulted in significant condensation of chromatin, shown as AVTD changes, which was similar to the effect of heat shock at 41 degrees C. No significant differences in responses between normal and hypersensitive subjects were detected. Neither 915 MHz nor 50 Hz exposure induced 53BP1 foci. On the contrary, a distinct decrease in background level of 53BP1 signaling was observed upon these exposures as well as after heat shock treatments. This decrease correlated with the AVTD data and may indicate decrease in accessibility of 53BP1 to antibodies because of stress-induced chromatin condensation. Apoptosis was determined by morphological changes and by apoptotic fragmentation of DNA as analyzed by pulsed-field gel electrophoresis (PFGE). No apoptosis was induced by exposure to 50 Hz and 915 MHz microwaves. In conclusion, 50 Hz magnetic field and 915 MHz microwaves under specified conditions of exposure induced comparable responses in lymphocytes from healthy and hypersensitive donors that were similar but not identical to stress response induced by heat shock.

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

    PubMed Central

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

    2016-01-01

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

  14. Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation

    PubMed Central

    Chiang, Yun; Tsai, Cheng-Hong; Kuo, Sung-Hsin; Liu, Chieh-Yu; Yao, Ming; Li, Chi-Cheng; Huang, Shang-Yi; Ko, Bor-Sheng; Lin, Chien-Ting; Hou, Hsin-An; Chou, Wen-Chien; Liu, Jia-Hau; Lin, Chien-Chin; Wu, Shang-Ju; Hsu, Szu-Chun; Chen, Yao-Chang; Lin, Kai-Hsin; Lin, Dong-Tsamn; Chou, Hsien-Tang; Lu, Meng-Yu; Yang, Yung-Li; Chang, Hsiu-Hao; Liu, Ming-Chih; Liao, Xiu-Wen; Wu, Jian-Kuen; Chou, Sheng-Chieh; Cheng, Chieh-Lung; Chen, Chien-Yuan; Tsay, Woei; Tien, Hwei-Fang; Tang, Jih-Luh; Chen, Yu-Hsuan

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy. PMID:27830767

  15. Genetic Variants in MTHFR Gene Predict ≥ 2 Radiation Pneumonitis in Esophageal Squamous Cell Carcinoma Patients Treated with Thoracic Radiotherapy

    PubMed Central

    Zhang, Jian; Li, Hongsheng; Qiao, Yumei; Huang, Chengsuo; Li, Baosheng

    2017-01-01

    Reactive oxygen species (ROS), formed as an indirect production of radiotherapy (RT), could cause DNA damage of normal tissues. Meanwhile, our body possesses the ability to restore the damage by DNA repair pathways. The imbalance between the two systems could finally result in radiation injury. Therefore, in this prospective cohort study, we explored the association of genetic variants in ROS metabolism and DNA repair pathway-related genes with radiation pneumonitis (RP). A total of 265 locally advanced esophageal squamous cell carcinoma (ESCC) patients receiving RT in Chinese Han population were enrolled. Five functional single nucleotide polymorphisms (SNPs) (rs1695 in GSTP1; rs4880 in SOD2; rs3957356 in GSTA1; and rs1801131, rs1801133 in MTHFR) were genotyped using the MassArray system, and rs1801131 was found to be a predictor of ≥ 2 RP. Our results showed that, compared with TT genotype, patients with GG/GT genotypes of rs1801131 had a notably lower risk of developing ≥ 2 RP (HR = 0.339, 95% CI = 0.137–0.839, P = 0.019). Further independent studies are required to confirm this findings. PMID:28046029

  16. The Combined Use of Inhaled and Intravenous Steroids for Children With Chemical Pneumonitis After Ingestion of Paint Thinner

    PubMed Central

    Konca, Capan; Tekin, Mehmet; Turgut, Mehmet

    2016-01-01

    Background Some studies in the literature support the use of either inhaled or systemic steroids for the treatment of chemical pneumonitis; however, no data have been published on the combined use of inhaled and intravenous (IV) steroids. Objectives This brief report describes the effective use of inhaled plus systemic steroids in managing six critical pediatric patients. Patients and Methods Medical records of patients were analyzed retrospectively. Results Of the six patients, 83.3% (n = 5) were male and 16.7% (n = 1) were female, with a mean age of 2.1 ± 0.49 years. The most common clinical signs were dyspnea (83.3%), fever (66.6%), and vomiting (66.6%). Owing to supportive treatments and the combined steroid treatment, respiratory distress diminished and there was no need for oxygen in any of the patients after 5 days. All patients were discharged without any sequelae. Conclusions The use of steroids in treating hydrocarbon pneumonias is still controversial. However, we suggest that the combined use of inhaled and intravenous steroids had positive effects on the clinical and radiological recovery of our patients. PMID:27651946

  17. Dentinal hypersensitivity: A comparative clinical evaluation of CPP-ACP F, sodium fluoride, propolis, and placebo

    PubMed Central

    Madhavan, Souparna; Nayak, Moksha; Shenoy, Amarnath; Shetty, Rajesh; Prasad, Krishna

    2012-01-01

    Background: Dentine hypersensitivity is a transient condition that often resolves with the natural sclerotic obturation of dentinal tubules. A potent topically applied in-office desensitizing treatment is indicated as the choice of treatment when dentine hypersensitivity is localized to one or two teeth. Aim: The present study aimed to evaluate and compare the clinical efficiency of CPP-ACP F, sodium fluoride, propolis, and distilled water that was used as placebo in treating dentinal hypersensitivity. Materials and Methods: 120 patients aged 20–40 years reporting with dentinal hypersensitivity in relation to canine, premolar and molars with erosion, abrasion, and gingival recession were randomly assigned to four groups of 30 patients each. Response to air jet and tactile stimuli were measured using visual analogue scale initially on 1st, 7th, 15th, 28th, 60th, and final assessment was done on the 90th day. Statistical Analysis: A statistical analysis was done using Anova test (Fischer's test) and Tukey HSD test for multicomparison. Results: The teeth treated with the test group showed decrease in the mean hypersensitivity values compared to control group, over a period of three months. The results showed propolis to be most efficient in treating dentinal hypersensitivity and CPP- ACPF showed to be the least efficient. Conclusion: All test groups were effective in reducing dentinal hypersensitivity, although they differed in rapidity of action over the period of 3 months. Further studies can be done using advanced materials and techniques. Multiple therapeutic modalities have been developed to treat dentinal hypersensitivity including products that impede nerve conduction of pain stimulus, products that mechanically occlude dentinal tubules, and calcium containing products designed to create plugs in the tubules utilizing a demineralization mechanism. PMID:23112475

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

    PubMed

    Noble, Suzanne

    2002-03-01

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

  19. Evaluation of the hypersensitivity potential of alternative butter flavorings.

    PubMed

    Anderson, Stacey E; Franko, Jennifer; Wells, J R; Lukomska, Ewa; Meade, B Jean

    2013-12-01

    Concern has been raised over the association of diacetyl with lung disease clinically resembling bronchiolitis obliterans in food manufacturing workers. This has resulted in the need for identification of alternative chemicals to be used in the manufacturing process. Structurally similar chemicals, 2,3-pentanedione, 2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione, used as constituents of synthetic flavoring agents have been suggested as potential alternatives for diacetyl, however, immunotoxicity data on these chemicals are limited. The present study evaluated the dermal irritation and sensitization potential of diacetyl alternatives using a murine model. None of the chemicals were identified as dermal irritants when tested at concentrations up to 50%. Similar to diacetyl (EC3=17.9%), concentration-dependent increases in lymphocyte proliferation were observed following exposure to all four chemicals, with calculated EC3 values of 15.4% (2,3-pentanedione), 18.2% (2,3-hexanedione), 15.5% (3,4-hexanedione) and 14.1% (2,3-heptanedione). No biologically significant elevations in local or total serum IgE were identified after exposure to 25-50% concentrations of these chemicals. These results demonstrate the potential for development of hypersensitivity responses to these proposed alternative butter flavorings and raise concern about the use of structurally similar replacement chemicals. Additionally, a contaminant with strong sensitization potential was found in varying concentrations in diacetyl obtained from different producers.

  20. Clinical Abacavir Hypersensitivity Reaction among Children in India.

    PubMed

    Chakravarty, Jaya; Sharma, Saurabh; Johri, Anuradha; Chourasia, Ankita; Sundar, Shyam

    2016-08-01

    Abacavir is currently recommended as a part of first line regimen by National AIDS Control Organization. The objective of this study was to observe the incidence of clinically diagnosed abacavir Hypersensitivity reaction (HSR) among children on abacavir based therapy in the National program. In this observational study, all children started on abacavir were included and HSR reaction was diagnosed clinically as per National guidelines. HLA- B*5701 testing was done in children diagnosed with clinical abacavir HSR. Among 101 children started on abacavir during the study period, 8 [7.9 % (95 % CI 3.5-15.0 %)] children developed clinically diagnosed abacavir HSR. All children with concomitant illness (4/8) were HLA-B*5701 negative. Only 2 (25 %, 2/8) carried HLA-B*5701 allele. Fever with abdominal symptoms as compared to respiratory symptoms were more common in HLA-B*5701 positive cases. Overdiagnosis of clinically diagnosed abacavir HSR is common and could be decreased by treating concomitant illness before starting abacavir.

  1. Evaluation of the hypersensitivity potential of alternative butter flavorings

    PubMed Central

    Anderson, Stacey E.; Franko, Jennifer; Wells, J.R.; Lukomska, Ewa; Meade, B. Jean

    2015-01-01

    Concern has been raised over the association of diacetyl with lung disease clinically resembling bronchiolitis obliterans in food manufacturing workers. This has resulted in the need for identification of alternative chemicals to be used in the manufacturing process. Structurally similar chemicals, 2,3-pentanedione, 2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione, used as constituents of synthetic flavoring agents have been suggested as potential alternatives for diacetyl, however, immunotoxicity data on these chemicals are limited. The present study evaluated the dermal irritation and sensitization potential of diacetyl alternatives using a murine model. None of the chemicals were identified as dermal irritants when tested at concentrations up to 50%. Similar to diacetyl (EC3 = 17.9%), concentration-dependent increases in lymphocyte proliferation were observed following exposure to all four chemicals, with calculated EC3 values of 15.4% (2,3-pentanedione), 18.2% (2,3-hexanedione), 15.5% (3,4-hexanedione) and 14.1% (2,3-heptanedione). No biologically significant elevations in local or total serum IgE were identified after exposure to 25–50% concentrations of these chemicals. These results demonstrate the potential for development of hypersensitivity responses to these proposed alternative butter flavorings and raise concern about the use of structurally similar replacement chemicals. Additionally, a contaminant with strong sensitization potential was found in varying concentrations in diacetyl obtained from different producers. PMID:24007741

  2. Immunologic mechanisms in hypersensitivity reactions to metal ions: an overview.

    PubMed

    Büdinger, L; Hertl, M

    2000-02-01

    Metal ions such as Ni2+, Co2+, Cu2+, or Cr3+ are haptens with a high immunogenic potential, as contact dermatitis caused by ionic metals occurs in about 10-15% of the human population. Since alloys containing Ni2+, Co2+, and Cr3+ are components of implants in replacement surgery, dentures, orthodontic wires, and various other devices, adverse reactions to metal ions create serious problems in practical medicine as incompatibility reactions to metal-containing biomaterials. On the other hand, contact dermatitis to metal ions such as Ni2+ is a well-established model for studying the molecular mechanisms involved in the recognition of haptens by the immune system. Although many investigations have been performed to elucidate the molecular interactions causing contact hypersensitivity in man, many aspects remain to be clarified. This review will focus on the experimental data accumulated so far on the immunologic mechanisms responsible for the recognition of metal ions by T cells and eliciting adverse immune reactions causing contact dermatitis.

  3. Chronic mouse model of TMA-induced contact hypersensitivity.

    PubMed

    Schneider, Claudia; Döcke, Wolf-Dietrich F; Zollner, Thomas M; Röse, Lars

    2009-04-01

    Due to the steadily increasing incidence of atopic dermatitis (AD), especially in children, there is a high medical need for new therapies and improved animal models. In mice, trimellitic anhydride (TMA) is routinely used to trigger T-cell-dependent contact hypersensitivity (CHS) reactions. In this study, we compared the standard acute TMA-induced CHS in Balb/c mice with subacute and chronic models of TMA-induced ear inflammation. Compared to the acute model, the chronic CHS model more closely reflects characteristics of AD, such as typical morphological changes of the inflamed skin, strong infiltration with T cells, major histocompatibility complex II-positive cells, eosinophils, and mast cells, a T-helper cell-type (Th) 2 cytokine profile and a strong increase of serum IgE levels. Moreover, a strong lymph node involvement with T-helper cell dominance and a mixed Th1/Th2 T-cell differentiation and activation pattern was demonstrated. Importantly, as demonstrated by successful therapy with prednisolone, the chronic TMA-induced CHS model, in contrast to acute and subacute models, made prolonged therapeutic treatment of a pre-established skin inflammation possible. Altogether, we present an improved model of mouse T-cell-dependent skin inflammation for AD. We hope this model will enhance the predictive value of animal models for therapeutic treatment of atopic eczema.

  4. Drug hypersensitivity reactions targeting the skin in dogs and cats.

    PubMed

    Voie, K L; Campbell, K L; Lavergne, S N

    2012-01-01

    Adverse drug reactions (ADRs) can be dose dependent or idiosyncratic. Most idiosyncratic reactions are believed to be immune-mediated; such drug hypersensitivities and allergies are unpredictable. Cutaneous reactions are the most common presentation of drug allergies. In veterinary medicine it can be difficult to assess the true prevalence of adverse drug reactions, although reports available suggest that they occur quite commonly. There are multiple theories that attempt to explain how drug allergies occur, because the pathogenesis is not yet well understood. These include the (pro)-hapten hypothesis, the Danger Theory, the pi concept, and the viral reactivation theory. Cutaneous drug allergies in veterinary medicine can have a variety of clinical manifestations, ranging from pruritus to often fatal toxic epidermal necrolysis. Diagnosis can be challenging, as the reactions are highly pleomorphic and may be mistaken for other dermatologic diseases. One must rely heavily on history and physical examination to rule out other possibilities. Dechallenge of the drug, histopathology, and other diagnostic tests can help to confirm the diagnosis. New diagnostic tools are beginning to be used, such as antibody or cellular testing, and may be used more in the future. There is much yet to learn about drug allergies, which makes future research vitally important. Treatment of drug allergies involves supportive care, and additional treatments, such as immunosuppressive medications, depend on the manifestation of the disease. Of utmost importance is to avoid the use of the incriminating drug in future treatment of the patient, as subsequent reactions can be worse, and ultimately can prove fatal.

  5. Specific immunoglobulin E in patients with immediate persulfate hypersensitivity.

    PubMed

    Aalto-Korte, Kristiina; Mäkinen-Kiljunen, Soili

    2003-07-01

    Persulfate salts may cause contact urticaria, allergic and irritant contact dermatitis, rhinitis and asthma. The mechanism of the immediate reactions has been unclear. Positive prick test, skin application and nasal and bronchial provocations identify immediate allergy. There is only 1 previous report of specific binding of immunoglobulin E (IgE) to ammonium persulfate demonstrated by radioallergosorbent test (RAST). In the present study, fresh 2% ammonium and potassium persulfate solutions were used for prick testing. Patients with positive prick tests were further evaluated with open skin application, immunospot and RAST. Prick testing with persulfate salts was performed in a total of 138 patients. 7 patients had a positive reaction to at least 1 persulfate salt. 6 of the patients had had skin symptoms, urticaria, eczema or angioedema, because of contact with hair bleaches. Open application on healthy skin was performed in 4 patients, and 3 out of them had urticarial reactions. The sera of 5 patients were investigated with immunospot and RAST. On immunospot, specific binding of IgE to human serum albumin (HSA)-conjugated ammonium and potassium persulfate was found in 2 patients. 1 immunospot-positive patient also had a positive RAST to ammonium persulfate-HSA conjugate. The mechanism of immediate hypersensitivity to persulfates thus seems to be IgE-mediated at least in some patients.

  6. In vitro methods for diagnosing nonimmediate hypersensitivity reactions to drugs.

    PubMed

    Mayorga, C; Sanz, M L; Gamboa, P; Garcia-Aviles, M C; Fernandez, J; Torres, M J

    2013-01-01

    Nonimmediate drug hypersensitivity reactions (DHRs) are difficult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and the lack of selective biological markers. In vitro methods are necessaryto establish a diagnosis, especially given the low sensitivity of skin tests and the inherent risks of drug provocation testing. In vitro evaluation of nonimmediate DHRs must include approaches that can be applied during the different phases of the reaction. During the acute phase, monitoring markers in both skin and peripheral blood helps to discriminate between immediate and nonimmediate DHRs with cutaneous responses and to distinguish between reactions that, although they present similar clinical symptoms, are produced by different immunological mechanisms and therefore have a different treatment and prognosis. During the resolution phase, in vitro testing is used to detect the response of T cells to drug stimulation; however, this approach has certain limitations, such as the lack of validated studies assessing sensitivity. Moreover, in vitro tests indicate an immune response that is not always related to a DHR. In this review, members of the Immunology and Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) provide an overview of the most widely used in vitro tests for evaluating nonimmediate DHRs.

  7. Diagnosing the tight building syndrome or diagnosing chemical hypersensitivity

    SciTech Connect

    Rogers, S.A. )

    1989-01-01

    The abrupt exposure to urea foam formaldehyde insulation served as an alert to its spectrum of symptoms, including attacks of headache, flushing, laryngitis, dizziness, nausea, extreme weakness or exhaustion, arthralgia, an inability to concentrate, unwarranted depression, arrhythmia, or muscle spasms, and baffled physicians from many specialties. Later it was learned that toluene, xylene, benzene, natural gas, trichloroethylene, and many other chemicals were also capable of triggering chemical hypersensitivity. Other names for this condition include Environmentally Induced Illness (EI), the Tight Building Syndrome (TBS), the Sick Building Syndrome, and Building-Related Illness. The very symptoms patients complain of can be provoked within minutes and then subsequently alleviated with an intradermal injection of the appropriate strength of the triggering chemical. This technique aids in convincing the patient of the EI or TBS triggers so that the patient can begin to relate symptoms to environmental exposures and initiate measure to bring the disease under control. The key to safer buildings is increased ventilation, increased filtration of air, and decreased use of off-gassing synthetic materials.

  8. Hypersensitivity to Aeroallergens in Patients with Nasobronchial Allergy

    PubMed Central

    Balaban, Jagoda; Bijelic, Radojka; Milicevic, Snjezana

    2014-01-01

    ABSTRACT Background: Aeroallergens are the most common causes of allergy. Aim: The aim of this study was to determine hypersensitivity to aeroallergens in patients with nasobronchial allergy. Methods: This retrospective population study included 2254 patients with nasobronchial allergy, from late adolescents to adults. Their response to aeroallergens was assessed by skin prick tests. Results: More patients had rhinitis (72.7%), than asthma (27.6%). Although majority of patients were female, allergy is more common in men than in women (p<0.05). Both groups of patients had the greatest number of positive skin prick tests for Dermatophagoides pteronyssinus (27.5%) and weed pollens (21.9%), followed by grass (18.3%) and tree pollens (10.1%). Ragweed is the most common positive weed pollen in both groups, more in patients with rhinitis (p=0.022). The cocksfoot is the most common grass pollen in rhinitis group (15.3%), but meadow grass (12.6%) in asthma patients. Birch is the most common tree allergen in the both groups. Conclusions: More patients with nasobronchial allergy have rhinitis than asthma. Skin prick tests are usually positive for Dermatophagoides pteronyssinus and weed pollens, followed by grass and tree pollens, and they are more common positive in patients with rhinitis than asthma. PMID:24937928

  9. Drug hypersensitivity reactions during hematopoietic stem cell transplantation.

    PubMed

    Bircher, Andreas J; Scherer Hofmeier, Kathrin

    2012-01-01

    Drugs may elicit a considerable variety of clinical signs, often affecting the skin and the mucous membranes. The most common are maculopapular exanthema, urticaria and angioedema. More rarely pustular, vesiculobullous, vasculitic and lichenoid lesions may be observed. Apart from the morphology, also the chronology of the occurrence and the evolution of the single skin lesions and the exanthema are paramount in the clinical diagnosis. Often, the skin is the only affected organ; however, it may herald a systemic involvement of internal organs, such as in severe drug-induced hypersensitivity syndromes or anaphylaxis. Cutaneous manifestations, particularly maculopapular exanthemas have a high incidence among patients treated with hematopoietic stem cell transplantation. In many cases, a virus- or drug-induced origin or a combination of both is responsible. However, the transplantation itself may also induce similar skin changes. These exanthemas include most often graft-versus-host disease, and rarely engraftment syndrome or eruption of lymphocyte recovery. The elucidation of the underlying cause of the exanthemas occurring in immune compromised patients and the determination of the correct diagnosis remain challenging. An extensive differential diagnosis has to be put forward. This includes several groups of disorders with sometimes very similar cutaneous manifestations. Manifestations form the underlying disease, complications from therapy, infections and drug reactions are the most common differential diagnoses.

  10. Re-visiting Hypersensitivity Reactions to Taxanes: A Comprehensive Review.

    PubMed

    Picard, Matthieu; Castells, Mariana C

    2015-10-01

    Taxanes (a class of chemotherapeutic agents) are an important cause of hypersensitivity reactions (HSRs) in cancer patients. During the last decade, the development of rapid drug desensitization has been key to allow patients with HSRs to taxanes to be safely re-treated although the mechanisms of these HSRs are not fully understood. Earlier studies suggested that solvents, such as Cremophor EL used to solubilize paclitaxel, were responsible for HSRs through complement activation, but recent findings have raised the possibility that some of these HSRs are IgE-mediated. Taxane skin testing, which identifies patients with an IgE-mediated sensitivity, appears as a promising diagnostic and risk stratification tool in the management of patients with HSRs to taxanes. The management of patients following a HSR involves risk stratification and re-exposure could be performed either through rapid drug desensitization or graded challenge based on the severity of the initial HSR and the skin test result. Rapid drug desensitization has been shown to be an effective and safe method to re-introduce taxanes in hundreds of patients, including those with life-threatening HSRs. Patients with non-severe delayed skin HSRs may benefit from rapid drug desensitization since they may be at increased risk for an immediate HSR upon re-exposure. This review focuses on the clinical presentation, diagnosis, and novel mechanisms of immediate HSRs to taxanes. A new management strategy for HSRs to taxanes based on skin testing and rapid drug desensitization is proposed.

  11. Dentine hypersensitivity: a review of its aetiology, pathogenesis and management.

    PubMed

    Sykes, L M

    2007-03-01

    Dentine hypersensitivity (DH) is defined as pain arising from exposed dentine and represents a distinct clinical entity. Reported cases are increasing particularly among the younger age groups and are thought to be due to acidogenic diets, destructive habits, poor tooth brushing techniques, and the increased use of tooth whitening products. Dentine exposure may be due to a number of processes, both physical and chemical, that lead to either loss of enamel/ cementum or loss of gingival tissue. These causative factors seldom act in isolation and include erosion, abrasion, attrition, abfraction, bruxing, bleaching, medication, ageing, genetic conditions, gingival recession, and periodontal disease or procedures. There are diverse range of treatment products available, which aim at either occluding the dentinal tubules or blocking the neural transmission from the pulp. Most reversible options make use of chemical agents such as fluorides, oxalate, strontium or potassium salts, or dentine-bonding agents. Non-reversible options should only be employed after one or more of the reversible options have been attempted. These usually involve placement of permanent restorations, occlusal adjustments or periodontal flap surgery. Careful diagnosis, patient counseling and management strategies are crucial to the success of any intervention.

  12. Diagnosis and management of immediate hypersensitivity reactions to cephalosporins.

    PubMed

    Dickson, Scott D; Salazar, Kimberly C

    2013-08-01

    Cephalosporins are one of the most commonly prescribed classes of antibiotics. Immediate IgE-mediated hypersensitivity reactions have been reported with use of a specific cephalosporin, as a cross-reaction between different cephalosporins or as a cross-reaction to other β-lactam antibiotics, namely, penicillin. Historically, frequent reports of anaphylaxis following administration of first- and second-generation cephalosporins to patients with a history of penicillin allergy led to the belief of a high degree of allergic cross-reactivity. More recent evidence reveals a significantly lower risk of cross-reactivity between penicillins and the newer-generation cephalosporins. The current thought is that a shared side chain, rather than the β-lactam ring structure, is the determining factor in immunologic cross-reactivity. Understanding the chemical structure of these agents has allowed us to identify the allergenic determinants for penicillin; however, the exact allergenic determinants of cephalosporins are less well understood. For this reason, standardized diagnostic skin testing is not available for cephalosporins as it is for penicillin. Nevertheless, skin testing to the cephalosporin in question, using a nonirritating concentration, provides additional information, which can further guide the work-up of a patient suspected of having an allergy to that drug. Together, the history and the skin test results can assist the allergist in the decision to recommend continued drug avoidance or to perform a graded challenge versus an induction of tolerance procedure.

  13. Treatment of Dentine Hypersensitivity by Diode Laser: A Clinical Study

    PubMed Central

    Umberto, Romeo; Claudia, Russo; Gaspare, Palaia; Gianluca, Tenore; Alessandro, Del Vecchio

    2012-01-01

    Introduction. Dentine hypersensitivity (DH) is characterized by pain after stimuli that usually provoke no symptoms. This study compared the effectiveness of GaAlAs diode laser alone and with topical sodium fluoride gel (NaF). Materials and Methods. The study was conducted on 10 patients (8 F/2 M, age 25–60) and 115 teeth with DH assessed by air and tactile stimuli measured by Numeric Rating Scale (NRS). Teeth were randomly divided into G1 (34 teeth) treated by 1.25% NaF; G2 (33 teeth) lased at 0.5 W PW (T on 100 m and T off 100 ms), fluence 62.2 J/cm2 in defocused mode with a 320 μ fiber. Each tooth received three 1′ applications; G3 (48 teeth) received NaF gel plus laser at same G2 parameters. NRS was checked at each control. Results. Significant pain reduction was showed. The NRS reduction percentages were calculated, and there was a concrete decrease of DH above all in G3 than G2 and G1. Conclusion. Diode laser is a useful device for DH treatment if used alone and mainly if used with NaF gel. PMID:22792109

  14. Studies of migration inhibition tests in penicillin hypersensitivity.

    PubMed Central

    Warrington, R J; Sauder, P J; Rutherford, W J

    1979-01-01

    The release of the migration inhibition factors, leucocyte inhibitory factor (LIF) and macrophage migration inhibition factor (MIF) from stimulated peripheral blood lymphocytes has been compared in patients with immediate (IgE-mediated) penicillin allergy and in patients with delayed hypersensitivity to tuberculin PPD. It has been shown that in these two groups of subjects, a comparable specific proliferative response can occur following stimulation with the appropriate drug (benzylpenicillin) or antigen (PPD). By cell fractionation studies, the proliferation was found to occur in the isolated T cell population in both subject groups. However, the lymphocyte response to benzylpenicillin was rarely associated with the release of LIF or MIF, in contrast to the situation in tuberculin sensitivity where a concomitant release of LIF and MIF was found. In about one third of penicillin allergic subjects, culture supernatants from specifically stimulated lymphocyte cultures induced migration inhibition in the indirect leucocyte migration test, but the inhibitory activity apparently resulted from the presence of penicillin-specific antibody and not from LIF. PMID:393437

  15. Concept of experimental preparation for treating dentin hypersensitivity

    PubMed Central

    Tanasiewicz, Marta; Gibas, Mirosław; Twardawa, Henryk; Machorowska-Pieniążek, Agnieszka

    2016-01-01

    Abstract Background Dentinal hypersensitivity (DH) is a diagnostic and therapeutic problem that is now appearing more frequently in modern dentistry. The aim of this work was to elaborate formulation of a new, original desensitizing preparation with prolonged action based on the knowledge of similar commercializations and to compare their performance in vitro. Methodology The analyses were performed with the aid of NMR spectroscopy. The experimental and commercial preparations were examined in vitro after thermocycling on human teeth by optical microscopy. The presence of the material on tooth tissue, its ability to penetrate into the tooth structure and its layer thickness were subjected to statistical analysis. Results A detailed knowledge on composition of commercial material was achieved from spectroscopic measurements. A new adhesive monomer was synthesized and incorporated into an experimental desensitizing formulation. The new monomer appeared to have comparable performance to the commercial one when regarding the affinity to tooth tissue and resistance to thermocycling. Conclusions The experimental formulation comprising a new adhesive monomer seems to be promising and could be applied in dental practice providing that biocompatibility is satisfactory. PMID:28352825

  16. Exploring Some Aspects Associated with Dentine Hypersensitivity in Children

    PubMed Central

    Shitsuka, Caleb; Mendes, Fausto Medeiros; Corrêa, Maria Salete Nahás Pires; Leite, Mariana Ferreira

    2015-01-01

    Background. The etiology of dentine hypersensitivity (DH) is still inconclusive and there are few studies concerning it in children. Aim. To evaluate clinical, dietary, and salivary variables in children with DH complaints. Design. Forty-eight children were asked about DH. Data regarding dietary habits were collected from the children's parents and an examination was performed to determine dental erosion. Dental biofilm was estimated by oral hygiene status, according to Greene and Vermillion's Simplified Oral Hygiene Index (OHI-S). Whole saliva was collected under mechanical stimulation and evaluated salivary flow rate, initial pH, buffer capacity, and calcium and phosphate concentrations. The temperature of soft drinks, drinking method, sense of bitter taste, and other variables were also determined. Possible factors associated with DH were analyzed by univariate and multiple Poisson regression analyses. The prevalence ratio (PR) values and 95% confidence intervals (95% CI) were calculated. Results. DH was associated with the presence of dental erosion (PR; 95% CI = 2.23; 1.05 to 4.71) and salivary flow rate (2.49; 1.05 to 5.91). When the presence of erosion was not included, other variables were retained as follows: bitter taste (2.36; 1.38 to 4.03), OHI-S (0.47; 0.23 to 0.97). Conclusion. DH in children is associated with factors related to dental erosion. PMID:25879070

  17. Neuron-glia crosstalk gets serious: Role in pain hypersensitivity

    PubMed Central

    Ren, Ke; Dubner, Ronald

    2009-01-01

    Purpose of review Recent studies show that peripheral injury activates both neuronal and non-neuronal or glial components of the peripheral and central cellular circuitry. The subsequent neuron-glial interactions contribute to pain hypersensitivity. This review will briefly discuss novel findings that have shed light on the cellular mechanisms of neuron-glial interactions in persistent pain. Recent findings Two fundamental questions related to neuron-glial interactions in pain mechanisms have been addressed: 1) what are the signals that lead to central glial activation after injury and 2) how glial cells affect CNS neuronal activity and promote hyperalgesia. Summary Evidence indicates that central glial activation depends on nerve inputs from the site of injury and release of chemical mediators. Hematogenous immune cells may migrate/infiltrate to the brain and circulating inflammatory mediators may penetrate the blood brain barrier to participate in central glial responses to injury. Inflammatory cytokines such as IL-1β released from glia may facilitate pain transmission through its coupling to neuronal glutamate receptors. This bidirectional neuron-glial signaling plays a key role in glial activation, cytokine production and the initiation and maintenance of hyperalgesia. Recognition of the contribution of the mutual neuron-glial interactions to central sensitization and hyperalgesia prompts new treatment for chronic pain. PMID:18784481

  18. Cross-sensitivity in a child with anticonvulsant hypersensitivity syndrome.

    PubMed

    Kwong, Karen L; Lam, Shu Yan; Lui, Ying Shun; Wong, Sik Nin; So, Kwan Tong

    2006-01-01

    We describe a fulminant picture of anticonvulsant hypersensitivity syndrome (AHS) and the possible role of nitrazepam. A 5-month-old boy developed fever and rash after the use of phenobarbitone. Allergy to phenobarbitone was suspected. Nitrazepam was substituted for seizure control. Over the next few days he progressively collapsed with fever, facial oedema and multi-organ involvement. The diagnosis of AHS was delayed because nitrazepam has not been implicated in the development of cross-sensitivity. AHS is a severe multi-organ reaction to aromatic anti-epileptic drugs. It has been thought to occur as a consequence of pre-existing pharmacogenetic and immunologic abnormalities. Careful selection of anti-epileptic drugs is essential as cross-sensitivity is common. Intermittent benzodiazepines have been recommended in managing breakthrough seizures in AHS. However, the structure of benzodiazepines contains aromatic rings and potential cross-reactivity cannot be totally ignored. Although we do not have direct proof, we believe that nitrazepam prolonged the clinical course.

  19. Jasmonic acid signaling modulates ozone-induced hypersensitive cell death.

    PubMed

    Rao, M V; Lee, H; Creelman, R A; Mullet, J E; Davis, K R

    2000-09-01

    Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent signaling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O(3)) exposure activates a hypersensitive response (HR)-like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling in influencing O(3)-induced cell death. Expression of salicylate hydroxylase (NahG) in Cvi-0 reduced O(3)-induced cell death. Methyl jasmonate (Me-JA) pretreatment of Cvi-0 decreased O(3)-induced H(2)O(2) content and SA concentrations and completely abolished O(3)-induced cell death. Cvi-0 synthesized as much JA as did Col-0 in response to O(3) exposure but exhibited much less sensitivity to exogenous Me-JA. Analyses of the responses to O(3) of the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic relationship between JA- and SA-signaling pathways in controlling the magnitude of O(3)-induced HR-like cell death.

  20. Examination of patients suspected as having hypersensitivity to iodinated contrast media with leukocyte migration test.

    PubMed

    Saito, Mikio; Abe, Manabu; Furukawa, Tomoyasu; Yagi, Motohiro; Koike, Yoshihiro; Wakasugi, Yutaka; Tabuchi, Norihiko; Uno, Katsuji

    2014-01-01

    In vivo tests may be used for the diagnosis of allergy to iodinated contrast media (ICM); however, the tests do not provide definitive diagnosis and are associated with risks for patients. Diagnoses based on in vitro tests are limited, and there are almost no relevant studies. Herein, the authors examined involvement of allergic reaction from a multilateral standpoint in 39 patients suspected of having ICM allergies using leukocyte migration test (LMT). The positive rate of LMT was 44%. A comparison with the positive rate of LMT in drugs other than ICM (74%) indicated 30% difference, which was significantly low value, suggesting that there is poor involvement of these drugs in the allergic reaction. In LMT positives, 76% of hypersensitivity reactions were skin rash mainly erythema, and 18% was anaphylactic reactions. Cases considered as non-immediate hypersensitivity accounted for about 4 times as many as immediate-type hypersensitivity. In examination of relevancy between a history of drugs or food allergies, the incidence of ICM allergies was 35%. There is a high possibility that these adverse reactions were caused by pseudoallergy to drug. It was suggested that most hypersensitivity reactions were skin rash related to non-immediate hypersensitivity, and approximately 20% of the reaction was immediate anaphylactic reaction. Therefore attention should be paid not only to immediate-type hypersensitivity but also delayed reactions. Moreover, it was considered that patients with past history of drug or food allergies have a high potential for manifestation of the reactions.

  1. Clinical guidelines for interstitial cystitis and hypersensitive bladder updated in 2015.

    PubMed

    Homma, Yukio; Ueda, Tomohiro; Tomoe, Hikaru; Lin, Alex Tl; Kuo, Hann-Chorng; Lee, Ming-Huei; Oh, Seung-June; Kim, Joon Chul; Lee, Kyu-Sung

    2016-07-01

    Clinical guidelines for interstitial cystitis and hypersensitive bladder have been updated as of 2015. The guidelines define interstitial cystitis by the presence of hypersensitive bladder symptoms (discomfort, pressure or pain in the bladder usually associated with urinary frequency and nocturia) and bladder pathology, after excluding other diseases explaining symptoms. Interstitial cystitis is further classified by bladder pathology; either Hunner type interstitial cystitis with Hunner lesions or non-Hunner type interstitial cystitis with mucosal bleeding after distension in the absence of Hunner lesions. Hypersensitive bladder refers to a condition, where hypersensitive bladder symptoms are present, but bladder pathology or other explainable diseases are unproven. Interstitial cystitis and hypersensitive bladder severely affect patients' quality of life as a result of disabling symptoms and/or comorbidities. Reported prevalence suggestive of these disorders varies greatly from 0.01% to >6%. Pathophysiology would be an interaction of multiple factors including urothelial dysfunction, inflammation, neural hyperactivity, exogenous substances and extrabladder disorders. Definite diagnosis of interstitial cystitis and hypersensitive bladder requires cystoscopy with or without hydrodistension. Most of the therapeutic options lack a high level of evidence, leaving a few as recommended therapeutic options.

  2. Formalin injection produces long-lasting hypersensitivity with characteristics of neuropathic pain.

    PubMed

    Salinas-Abarca, Ana Belen; Avila-Rojas, Sabino Hazael; Barragán-Iglesias, Paulino; Pineda-Farias, Jorge Baruch; Granados-Soto, Vinicio

    2017-02-15

    The purpose of this study was to investigate whether 1%, 2% or 5% formalin injection produce hypersensitivity with characteristics of the neuropathic pain induced by spinal nerve injury. Formalin injection (1%, 2% and 5%) produced concentration-dependent long-lasting (at least 14 days) mechanical allodynia and hyperalgesia in both paws. Likewise, L5/L6 spinal nerve ligation induced allodynia and hyperalgesia in both paws. The intensity of hypersensitivity was greater in the ipsilateral than in the contralateral paw in all models. Systemic gabapentin or morphine completely reduced 1% formalin-induced hypersensitivity. In contrast, both drugs were not able to fully diminish 2-5% formalin- and nerve injury-induced hypersensitivity. Indomethacin produced a significant effect in the chronic 1% formalin test. Conversely, this drug did not modify 2 or 5% formalin- and nerve injury-induced hypersensitivity. Spinal nerve injury and 2-5%, but not 1%, formalin injection enhanced ATF3 protein expression and immunofluorescence in dorsal root ganglia (DRG) in a time-dependent manner. Furthermore, 2-5%, but not 1%, formalin injection or spinal nerve injury also enhanced α2δ-1 subunit protein levels in DRG. Our results suggest that 5% and, at lesser extent, 2% formalin injection produces long-lasting hypersensitivity with a pharmacological and molecular pattern that resembles neuropathic pain induced by spinal nerve ligation.

  3. Juvenile rheumatoid arthritis: cellular hypersensitivity and selective IgA deficiency

    PubMed Central

    Panush, R. S.; Bianco, N. E.; Schur, P. H.; Rocklin, R. E.; David, J. R.; Stillman, J. S.

    1972-01-01

    Although humoral immune mechanisms are currently thought to be of pathogenetic significance in juvenile rheumatoid arthritis (JRA), little is known about the role of cellular hypersensitivity in this disease. A possible association between abnormalities of humoral and cellular immunity exists in patients with ataxia-telangiectasia, who may have absent IgA, abnormal delayed hypersensitivity, or both. As IgA deficiency has been noted in 2–3% of patients with JRA, we have studied selected aspects of humoral and cellular hypersensitivity in patients with JRA and IgA deficiency and in patients with JRA and normal IgA levels. All patients had normal serum levels of complement, IgG, IgM, and IgD. Cellular hypersensitivity was evaluated by cutaneous delayed-type hypersensitivity, in vitro migration inhibitory factor production, and antigen induced 3H-thymidine incorporation by lymphocytes using Candida and Streptokinase–Streptodornase antigens. Two of four IgA deficient patients had positive in vitro but negative in vivo responses to antigens. Seven of fourteen JRA patients with normal immunoglobulin levels exhibited a similar dissociation of in vivo and in vitro manifestations of delayed hypersensitivity. This pattern of cellular immune response was associated with activity and chronicity of disease; it was independent of IgA deficiency. PMID:5022450

  4. Desensitization in delayed drug hypersensitivity reactions -- an EAACI position paper of the Drug Allergy Interest Group.

    PubMed

    Scherer, K; Brockow, K; Aberer, W; Gooi, J H C; Demoly, P; Romano, A; Schnyder, B; Whitaker, P; Cernadas, J S R; Bircher, A J

    2013-07-01

    Drug hypersensitivity may deprive patients of drug therapy, and occasionally no effective alternative treatment is available. Successful desensitization has been well documented in delayed drug hypersensitivity reactions. In certain situations, such as sulfonamide hypersensitivity in HIV-positive patients or hypersensitivity to antibiotics in patients with cystic fibrosis, published success rates reach 80%, and this procedure appears helpful for the patient management. A state of clinical tolerance may be achieved by the administration of increasing doses of the previously offending drug. However, in most cases, a pre-existent sensitization has not been proven by positive skin tests. Successful re-administration may have occurred in nonsensitized patients. A better understanding of the underlying mechanisms of desensitization is needed. Currently, desensitization in delayed hypersensitivity reactions is restricted to mild, uncomplicated exanthems and fixed drug eruptions. The published success rates vary depending on clinical manifestations, drugs, and applied protocols. Slower protocols tend to be more effective than rush protocols; however, underreporting of unsuccessful procedures is very probable. The decision to desensitize a patient must always be made on an individual basis, balancing risks and benefits. This paper reviews the literature and presents the expert experience of the Drug Hypersensitivity Interest Group of the European Academy of Allergy and Clinical Immunology.

  5. Visceral and somatic hypersensitivity in TNBS-induced colitis in rats.

    PubMed

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

    2008-02-01

    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 (200-250 g) 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 tests were used to evaluate for visceral, mechanical, and thermal sensitivity. The rats demonstrated visceral hypersensitivity at 2-28 days following TNBS administration (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.

  6. Use of RAST technique in wasp sting hypersensitivity. Cross-reactions between various insect antigens are specially considered.

    PubMed

    Müller, U; Roth, A; Yman, L; Patrizzi, R

    1978-08-01

    Clinical hypersensitivity to wasp stings was found to be fairly well correlated with the presence of serum IgE-antibodies against yellow jacket venom as detected by the RAST technique. Such antibodies were never found in a control group of non-allergic blood donors, but they were detected in a surprisingly large proportion of patients with bee sting allergy without known allergic reactions to wasps. Studies using RAST inhibition technique failed to prove cross-reactions between bee and wasp venoms. Considerably better results were obtained when venom antigens instead of whole body antigens were used in the RAST. RAST inhibition studies suggested that IgE-antibodies detected with RAST using whole body antigen are directed against bee venom constituents in the whole body extract.

  7. Pharmacological attenuation of chronic alcoholic pancreatitis induced hypersensitivity in rats

    PubMed Central

    McIlwrath, Sabrina L; Westlund, Karin N

    2015-01-01

    AIM: To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices. METHODS: Experimental rats were fed a modified Lieber-DeCarli alcohol (6%) and high-fat (65%) diet (AHF) for 10 wk while control animals received a regular rodent chow diet. Weekly behavioral tests determined mechanical and heat sensitivity. In week 10 a fasting glucose tolerance test was performed, measuring blood glucose levels before and after a 2 g/kg bodyweight intraperitoneal (i.p.) injection of glucose. Post mortem histological analysis was performed by staining pancreas and liver tissue sections with hematoxylin and eosin. Pancreas sections were also stained with Sirius red and fast green to quantify collagen content. Insulin-expressing cells were identified immunohistochemically in separate sections. Tissue staining density was quantified using Image J software. After mechanical and heat sensitivity became stable (weeks 6-10) in the AHF-fed animals, three different drugs were tested for their efficacy in attenuating pancreatitis associated hypersensitivity: a Group II metabotropic glutamate receptor specific agonist (2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate (APDC, 3 mg/kg, ip; Tocris, Bristol, United Kingdom), nociceptin (20, 60, 200 nmol/kg, ip; Tocris), and morphine sulfate (3 mg/kg, μ-opioid receptor agonist; Baxter Healthcare, Deerfield, IL, United States). RESULTS: Histological analysis of pancreas and liver determined that unlike control rats, AHF fed animals had pancreatic fibrosis, acinar and beta cell atrophy, with steatosis in both organs. Fat vacuolization was significantly increased in AHF fed rats (6.4% ± 1.1% in controls vs 23.8% ± 4.2%, P < 0.05). Rats fed the AHF diet had reduced fasting glucose tolerance in week 10 when peak blood glucose levels reached significantly higher concentrations than controls (127.4 ± 9.2 mg/dL in controls vs 161.0 ± 8.6 mg/dL, P < 0.05). This concurred with a 3.5 fold higher

  8. The microwave syndrome or electro-hypersensitivity: historical background.

    PubMed

    Carpenter, David O

    2015-01-01

    Microwave generating equipment first became common during World War 2 with the development of radar. Soviet bloc countries reported that individuals exposed to microwaves frequently developed headaches, fatigue, loss of appetite, sleepiness, difficulty in concentration, poor memory, emotional instability, and labile cardiovascular function, and established stringent exposure standards. For a variety of reasons these reports were discounted in Western countries, where the prevailing belief was that there could be no adverse health effects of electromagnetic fields (EMFs) that were not mediated by tissue heating. The reported Soviet effects were at lower intensities than those that cause heating. However, there were several accidental exposures of radar operators in Western countries that resulted in persistent symptoms similar to those described above. The Soviets irradiated the US Embassy in Moscow with microwaves during the period 1953-1975, and while no convincing evidence of elevated cancer rates was reported, there were reports of "microwave illness". Officials passed these complaints off as being due to anxiety, not effects of the microwave exposure. There is increasing evidence that the "microwave syndrome" or "electro-hypersensitivity" (EHS) is a real disease that is caused by exposure to EMFs, especially those in the microwave range. The reported incidence of the syndrome is increasing along with increasing exposure to EMFs from electricity, WiFi, mobile phones and towers, smart meters and many other wireless devices. Why some individuals are more sensitive is unclear. While most individuals who report having EHS do not have a specific history of an acute exposure, excessive exposure to EMFs, even for a brief period of time, can induce the syndrome.

  9. Cellular Tests for the Evaluation of Drug Hypersensitivity.

    PubMed

    Ariza, Adriana; Montanez, Maria I; Fernandez, Tahia D; Perkins, James R; Mayorga, Cristobalina

    2016-01-01

    The diagnosis of drug hypersensitivity reactions (DHR) is complex, with many potential pitfalls. Although the use of clinical history and skin testing can be valuable, drug provocation testing (DPT) remains the gold standard for many DHR. However, DPT carries some potential risk and should not be performed for severe reactions. There is therefore a general consensus on the need to improve in vitro tests to achieve safe and accurate diagnosis of DHR. A range of in vitro approaches can be applied depending on the type of reaction and the immunological mechanism involved, i.e. IgE- or T-cell-mediated. However, commercially available tests only exist for a handful of drugs, and only for drugs that provoke IgEmediated DHR. Of the cellular tests that focus on the identification of the culprit drug, the best validated is the basophil activation test used for evaluating IgE-mediated reactions. For T-cell-mediated DHR, the lymphocyte transformation test and enzyme-linked immunosorbent spot appear to be the most promising. However, these tests often show low sensitivity. Despite their current drawbacks, in vitro tests can complement in vivo testing and further work in this area will be crucial to improve our current arsenal of tools for the detection and assessment of DHR. For this, the use of appropriate and relevant drug metabolites as well as other factors that can amplify the cell response as well as the use of multiple tests in concert key to improving in vitro diagnosis. Such improvements will be crucial to diagnose patients with severe reactions for whom DPT cannot be performed.

  10. The role for decorin in delayed-type hypersensitivity

    PubMed Central

    Seidler, Daniela G.; Mohamed, Negia A.; Bocian, Carla; Stadtmann, Anika; Hermann, Sven; Schäfers, Klaus; Schäfers, Michael; Iozzo, Renato V.; Zarbock, Alexander; Götte, Martin

    2016-01-01

    Decorin, a small leucine-rich proteoglycan, regulates extracellular matrix organization, growth factor-mediated signaling and cell growth. As decorin may directly modulate immune responses, we investigated its role in a mouse model of contact allergy (oxazolone-mediated delayed-type hypersensitivity, DTH) in decorin-deficient (Dcn−/−) and wild-type mice. Dcn−/− mice showed a reduced ear swelling 24 hours after oxazolone treatment with a concurrent attenuation of leukocyte infiltration. These findings were corroborated by reduced glucose metabolism as determined by 18FDG uptake in positron emission tomography scans. Unexpectedly, polymorphonuclear leukocyte numbers in Dcn−/− blood vessels were significantly increased, accompanied by large numbers of flattened leukocytes adherent to the endothelium. Intravital microscopy, flow chamber and static adhesion assays confirmed increased adhesion and reduced transmigration of Dcn−/− leukocytes. Circulating blood neutrophil numbers were significantly increased in Dcn−/− mice 24 hours after DTH elicitation, but only moderately increased in wild-type mice. Expression of the pro-inflammatory cytokine TNF-α was reduced, while syndecan-1 and ICAM-1 were overexpressed in inflamed ears of Dcn−/− mice, indicating that these adhesion molecules could be responsible for increased leukocyte adhesion. Decorin treatment of endothelial cells increased tyrosine phosphorylation and reduced syndecan-1 expression. Notably, absence of syndecan-1 in a genetic background lacking decorin rescued the attenuated DTH phenotype of Dcn−/− mice. Collectively, these results implicate a role for decorin in mediating DTH responses by influencing polymorphonuclear leukocyte attachment to the endothelium. This occurs via two non-mutually exclusive mechanisms that involve a direct anti-adhesive effect on polymorphonuclear leukocytes and a negative regulation of ICAM-1 and syndecan-1 expression. PMID:22043007

  11. Biomaterial Hypersensitivity: Is It Real? Supportive Evidence and Approach Considerations for Metal Allergic Patients following Total Knee Arthroplasty

    PubMed Central

    Mihalko, William M.; Grupp, Thomas M.; Manning, Blaine T.; Dennis, Douglas A.; Goodman, Stuart B.; Saleh, Khaled J.

    2015-01-01

    The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected. PMID:25883940

  12. Evaluation of the Effect of Low Level Laser Therapy Toothbrush in Treatment of Dentin Hypersensitivity

    PubMed Central

    Yaghini, Jaber; Mogharehabed, Ahmad; Safavi, Nassimeh; Mohamadi, Mehrnush; Ashtiju, Fahime

    2015-01-01

    Introduction: Dentin hypersensitivity is one of the most common complications that affect patients after periodontal therapy. Recently low level laser therapy has been introduced as a new treatment modality and has produced beneficial results. The purpose of this study is to evaluate the effect of low level laser therapy toothbrushes in reduction of dentin hypersensitivity. Methods: In this pilot interventional controlled clinical trial, 40 patients suffering from dentin hypersensitivity were selected using simple randomization. Half of the patients were given laser toothbrushes and the other half was given non-laser sensodyne toothbrushes. Primary dentin hypersensitivity was recorded by visual analogue scale (VAS) score and ice spray. Then dentin hypersensitivity was measured right after the treatment as well az in the intervals of 1 month and 2 months after initiation of the study. Data were compared using Statistical Package for the Social Sciences (SPSS) software and Analysis of variance (ANOVA) paired T test. Results: The results of this study showed that there was a significant difference in each of the two kinds of tooth brushes separately for all time intervals (P < 0.001). Also the effect of the type of toothbrush was investigated using before treatment VAS with covariance analyses. P values for immediately, 1 month and 2 months after treatment were calculated to be 0.078, 0.02, 0.01 respectfully. Also the effect of the toothbrush type was significant in the manner that laser toothbrushes reduce dentin hypersensitivity more than ordinary toothbrushes (P< 0.05). Conclusion: Both sensodyne and laser tooth brushes improve dentin hypersensitivity, although the laser toothbrush led to better results in short. PMID:25987974

  13. Professional exposure to goats increases the risk of pneumonic-type lung adenocarcinoma: results of the IFCT-0504-Epidemio study.

    PubMed

    Lutringer-Magnin, Delphine; Girard, Nicolas; Cadranel, Jacques; Leroux, Caroline; Quoix, Elisabeth; Cottin, Vincent; Del Signore, Corinne; Lebitasy, Marie-Paule; Cordier, Geneviève; Vanhems, Philippe; Mornex, Jean-François

    2012-01-01

    Pneumonic-type lung adenocarcinoma (P-ADC) represents a distinct subset of lung cancer with specific clinical, radiological, and pathological features. Given the weak association with tobacco-smoking and the striking similarities with jaagsiekte sheep retrovirus (JSRV)-induced ovine pulmonary adenocarcinoma, it has been suggested that a zoonotic viral agent infecting pulmonary cells may predispose to P-ADC in humans. Our objective was to explore whether exposure to domestic small ruminants may represent a risk factor for P-ADC. We performed a multicenter case-control study recruiting patients with P-ADC as cases and patients with non-P-ADC non-small cell lung cancer as controls. A dedicated 356-item questionnaire was built to evaluate exposure to livestock. A total of 44 cases and 132 controls were included. At multivariate analysis, P-ADC was significantly more associated with female gender (Odds-ratio (OR) = 3.23, 95% confidence interval (CI): 1.32-7.87, p = 0.010), never-smoker status (OR = 3.57, 95% CI: 1.27-10.00, p = 0.015), personal history of extra-thoracic cancer before P-ADC diagnosis (OR = 3.43, 95% CI: 1.10-10.72, p = 0.034), and professional exposure to goats (OR = 5.09, 95% CI: 1.05-24.69, p = 0.043), as compared to other subtypes of lung cancer. This case-control suggests a link between professional exposure to goats and P-ADC, and prompts for further epidemiological evaluation of potential environmental risk factors for P-ADC.

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

    SciTech Connect

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

    2013-10-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    SciTech Connect

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

    2013-03-15

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

  17. Nickel hypersensitivity and orthodontic treatment: a systematic review and meta-analysis.

    PubMed

    Gölz, Lina; Papageorgiou, Spyridon N; Jäger, Andreas

    2015-07-01

    Nickel-containing alloys are widely used in orthodontic appliances, even though nickel is by far the most common contact allergen. However, the scientific evidence concerning allergic reactions to nickel in orthodontic patients has not been evaluated systematically. The objective of this study was to investigate whether the prevalence of nickel hypersensitivity is affected by orthodontic treatment. Unrestricted electronic and manual searches were performed until July 2013 for human clinical studies assessing orthodontic treatment and nickel hypersensitivity. Methodological limitations were evaluated with the Downs and Black tool. Crude and adjusted odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated from random-effects meta-analyses, followed by subgroup and sensitivity analyses. Thirty studies were included in the review, and 24 datasets with 10 184 patients in the meta-analyses. Orthodontic treatment had no significant effect on nickel hypersensitivity (n = 11; crude OR 0.99; 95%CI: 0.78-1.25; p = 0.914). However, when confounding from factors such as sex and piercings was taken into account, orthodontic treatment was associated with a lower risk of hypersensitivity (n = 1; adjusted OR 0.60; 95%CI: 0.40-0.80; p < 0.001). This was even more pronounced when orthodontic treatment was performed prior to piercing (n = 7; crude OR 0.35; 95%CI: 0.24-0.50; p < 0.001). Orthodontic treatment seems to have a protective role against nickel hypersensitivity, especially when it precedes piercings.

  18. BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit.

    PubMed

    Wang, Peng; Du, Chao; Chen, Fei-Xue; Li, Chang-Qing; Yu, Yan-Bo; Han, Ting; Akhtar, Suhail; Zuo, Xiu-Li; Tan, Xiao-Di; Li, Yan-Qing

    2016-02-03

    The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF(+/-) mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently, and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity, and this process is likely initiated by BDNF-TrkB pathway activation.

  19. Low-level laser therapy of dentin hypersensitivity: a short-term clinical trial.

    PubMed

    Orhan, Kaan; Aksoy, Umut; Can-Karabulut, Deniz C; Kalender, Atakan

    2011-09-01

    The aim of this study was to evaluate low-level laser therapy in cervical dentin hypersensitivity. A randomized controlled clinical trial was conducted with a total of 64 teeth. Dentin desensitizer and diode laser were applied on the cervical dentin surfaces. Distilled water and placebo laser was used as the placebo groups. The irradiance used was 4 J/cm(2) per treatment site. The baseline measurement of hypersensitivity was made by using visual analog scale (VAS). Twenty-four hours and 7 days after the application of desensitizer, diode laser and placebo groups, a new VAS analysis was conducted for the patients' sensitivity level. The mean pain scores of placebo groups were significantly higher than the desensitizer's and diode laser's mean scores (ANOVA, p < 0.05). The VAS analysis revealed a significant decrease in dentin hypersensitivity in 7 days with the use of the desensitizer and low-level laser therapy and no statistically significant difference was observed between these two treatments (p > 0.05). Although low-level laser and glutaraldehyde containing desensitizer present distinct modes of action, experimental agents caused a significant reduction of dentin hypersensitivity without showing secondary effects, not irritating the pulp or causing pain, not discoloring or staining the teeth, and not irritating the soft tissues at least for a period of 1 week with no drawbacks regarding handling and/or ease of application. Low-level laser therapy and desensitizer application had displayed similar effectiveness in reducing moderate dentin hypersensitivity.

  20. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease

    PubMed Central

    Wang, Bing; Chen, Li-Hua

    2016-01-01

    In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain. PMID:27747105

  1. [Hypersensitivity to pollen of Olea europea in patients with pollen allergy in Zadar County, Croatia].

    PubMed

    Skitarelić, Natasa; Mazzi, Antun; Skitarelić, Neven; Misulić, Josko; Vuletić, Ana

    2010-06-01

    Olive pollen is one of the most common respiratory allergens in the Mediterranean countries. The aim of this study was to establish the frequency of hypersensitivity to the pollen of Olea europea in pollen allergic patients in the County of Zadar. The study included 671 patients with pollen allergy; 61 % were male and 39 % female. 53.5 % were children aged from 4 to 14 years and 46.5 % adolescents and adults from 15 to 59 years. We took their case history, clinically examined them, and tested using the skin prick test and enzymo-immunologic UniCAP test for specific IgE antibodies. For statistical analysis we used the chi-square test. Hypersensitivity to Olea europea pollen was confirmed in 8.8 % patients with pollen allergy. Among them, the most prevalent symptom was rhinitis (58 %). Most hypersensitive patients were urban residents. Only 3 % patients lived on an island. Judging by available data, our findings show the lowest hypersensitivity to olive pollen in the Mediterranean. A comparison with our two earlier studies did not show any fluctuation in this kind of hypersensitivity.

  2. Isolation of uvh1, an Arabidopsis mutant hypersensitive to ultraviolet light and ionizing radiation.

    PubMed Central

    Harlow, G R; Jenkins, M E; Pittalwala, T S; Mount, D W

    1994-01-01

    A genetic screen for mutants of Arabidopsis that are hypersensitive to UV light was developed and used to isolate a new mutant designated uvh1. UV hypersensitivity in uvh1 was due to a single recessive trait that is probably located on chromosome 3. Although isolated as hypersensitive to an acute exposure to UV-C light, uvh1 was also hypersensitive to UV-B wavelengths, which are present in sunlight that reaches the earth's surface. UV-B damage to both wild-type and uvh1 plants could be significantly reduced by subsequent exposure of UV-irradiated plants to photoreactivating light, showing that photoreactivation of UV-B damage is important for plant viability and that uvh1 plants are not defective in photoreactivation. A new assay for DNA damage, the Dral assay, was developed and used to show that exposure of wild-type and uvh1 plants to a given dose of UV light induces the same amount of damage in chloroplast and nuclear DNA. Thus, uvh1 is not defective in a UV protective mechanism. uvh1 plants were also found to be hypersensitive to ionizing radiation. These results suggest that uvh1 is defective in a repair or tolerance mechanism that normally provides plants with resistance to several types of DNA damage. PMID:8148646

  3. A case of chlorpheniramine maleate-induced hypersensitivity with aspirin intolerance.

    PubMed

    Kim, Min-Hye; Lee, Sang-Min; Lee, So-Hee; Kwon, Hyouk-Soo; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Chang, Yoon-Seok

    2011-01-01

    Antihistamines are commonly used to treat allergic disease, such as allergic rhinitis, urticaria, and angioedema. Although several previous reports describe hypersensitivity to antihistamines such as cetirizine and hydroxyzine, documented cases of chlorpheniramine hypersensitivity are extremely rare. Here, we report the case of a 45-year-old Korean woman who presented with urticaria after ingesting a cold medication. Over the previous 5 years, she had also experienced a food allergy to crab and shrimp, allergic rhinitis, and repeated urticaria after ingesting cold medication. Provocation with aspirin elicited generalized urticaria. Intravenous chlorpheniramine and methylprednisolone was injected for symptom control, but in fact appeared to aggravate urticaria. A second round of skin and provocation tests for chlorpheniramine and methylprednisolone showed positive results only for chlorpheniramine. She was diagnosed with aspirin intolerance and chlorpheniramine hypersensitivity, and was instructed to avoid these drugs. To date, this is the second of only two cases of chlorpheniramine-induced type I hypersensitivity with aspirin intolerance. Although the relationship between aspirin intolerance and chlorpheniramine-induced type I hypersensitivity is unclear, physicians should be aware of the possibility of urticaria or other allergic reactions in response to antihistamines.

  4. Blockade of metabotropic glutamate receptor 5 activation inhibits mechanical hypersensitivity following abdominal surgery.

    PubMed

    Dolan, Sharron; Nolan, Andrea Mary

    2007-08-01

    This study used the metabotropic glutamate 5 (mGlu5) receptor subtype-selective antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) to characterise the contribution of mGlu5 receptor activity to pain and hypersensitivity in an animal model of post-surgical pain. Adult female Wistar rats (200-250g) were anaesthetised with isoflurane (2%) and underwent a midline laparotomy with gentle manipulation of the viscera, and the effects of pre- (30min) or post- (5h) operative treatment with MPEP (1, 3 or 10mgkg(-1); i.p.) or drug-vehicle on hindpaw withdrawal latency (in seconds) to thermal stimulation (Hargreave's Test) and response threshold (in grams) to mechanical stimulation (using a dynamic plantar aesthesiometer) were measured. Animals that underwent surgery displayed significant hypersensitivity to mechanical stimulation of the hindpaws. Hypersensitivity was maximum at 6h post-surgery (44.5+/-2.4% decrease; p<0.01 vs. anaesthesia only controls) and persisted for 48h. Surgery had no effect on thermal withdrawal latency. Both pre-operative and post-operative administration of 10mgkg(-1)MPEP blocked mechanical hypersensitivity induced by surgery (p<0.01 vs. vehicle treatment). MPEP had no effect on acute nociceptive thresholds in naïve animals. These data suggest that activity at mGlu5 receptors contributes to development of pain and hypersensitivity following surgery.

  5. Observations on dentine hypersensitivity in general dental practices in the United Arab Emirates

    PubMed Central

    Al-Khafaji, Hasanain

    2013-01-01

    Dentine hypersensitivity is a common clinical finding with a wide variation in prevalence values and etiological factors. The objective of this cross-sectional study was to investigate the prevalence and some etiological factors of dentine hypersensitivity of Emirati patients visiting general dental clinics in the United Arab Emirates (UAE) over a period of three calendar months. Materials and Methods: Six general dental practitioners examined 204 Emirati patients over a period of three calendar months and patients who had dentine hypersensitivity diagnosed were questioned further about their smoking habits and the frequency, severity, and duration of their pain. Furthermore, cervical tooth surface loss was noted. Results: A total of 55 patients were diagnosed as having dentine hypersensitivity, giving a prevalence figure of 27%. The most common teeth affected were the lower anterior teeth. Conclusions: The prevalence of dentine hypersensitivity in Emirati patients visiting a general dental clinic in the UAE was 27%. The most common etiology appeared to be the loss of cervical tooth surface structure. PMID:24932110

  6. BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit

    PubMed Central

    Wang, Peng; Du, Chao; Chen, Fei-Xue; Li, Chang-Qing; Yu, Yan-Bo; Han, Ting; Akhtar, Suhail; Zuo, Xiu-Li; Tan, Xiao-Di; Li, Yan-Qing

    2016-01-01

    The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF+/− mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently, and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity, and this process is likely initiated by BDNF-TrkB pathway activation. PMID:26837784

  7. Anti-inflammatory and immune-regulatory mechanisms prevent contact hypersensitivity to Arnica montana L.

    PubMed

    Lass, Christian; Vocanson, Marc; Wagner, Steffen; Schempp, Christoph M; Nicolas, Jean-Francois; Merfort, Irmgard; Martin, Stefan F

    2008-10-01

    Sesquiterpene lactones (SL), secondary plant metabolites from flowerheads of Arnica, exert anti-inflammatory effects mainly by preventing nuclear factor (NF)-kappaB activation because of alkylation of the p65 subunit. Despite its known immunosuppressive action, Arnica has been classified as a plant with strong potency to induce allergic contact dermatitis. Here we examined the dual role of SL as anti-inflammatory compounds and contact allergens in vitro and in vivo. We tested the anti-inflammatory and allergenic potential of SL in the mouse contact hypersensitivity model. We also used dendritic cells to study the activation of NF-kappaB and the secretion of interleukin (IL)-12 in the presence of different doses of SL in vitro. Arnica tinctures and SL potently suppressed NF-kappaB activation and IL-12 production in dendritic cells at high concentrations, but had immunostimulatory effects at low concentrations. Contact hypersensitivity could not be induced in the mouse model, even when Arnica tinctures or SL were applied undiluted to inflamed skin. In contrast, Arnica tinctures suppressed contact hypersensitivity to the strong contact sensitizer trinitrochlorobenzene and activation of dendritic cells. However, contact hypersensitivity to Arnica tincture could be induced in acutely CD4-depleted MHC II knockout mice. These results suggest that induction of contact hypersensitivity by Arnica is prevented by its anti-inflammatory effect and immunosuppression as a result of immune regulation in immunocompetent mice.

  8. Colonic mast cell infiltration in rats with TNBS-induced visceral hypersensitivity.

    PubMed

    Ohashi, Katsuyo; Sato, Yasushi; Iwata, Hiroshi; Kawai, Mitsuhisa; Kurebayashi, Yoichi

    2007-12-01

    Colonic mucosal mast cells are implicated in the pathogenesis of visceral hypersensitivity associated with irritable bowel syndromes. This study was designed to investigate the roles of mucosal mast cells in development of an experimental visceral hypersensitivity induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats. TNBS, when injected into the proximal colon through laparotomy, produced a significant decrease in pain threshold of the distal colon to mechanical distention, indicating a visceral hypersensitivity. In the proximal colon that was directly insulted by TNBS, mucosal necrosis and extensive inflammatory cell infiltration were observed with concomitant increase in tissue myeloperoxide (MPO) activity. In the distal colon where distention stimuli were applied, the number of mucosal mast cells significantly increased following TNBS treatment, although neither mucosal injury nor increase in tissue MPO activity was observed. In an organ culture, spontaneous release of a mucosal mast cell-specific protease (RMCP-2) from the distal colon tissue of TNBS-treated rats was significantly larger than that of sham animals. Furthermore, TNBS-induced visceral hypersensitivity was significantly suppressed by subcutaneous pretreatment with a mast cell stabilizer doxantrazole in a dose-dependent manner. These findings suggest that prominent colonic mast cell infiltration associated with an enhanced spontaneous mediator release is responsible, at least partly, for development of visceral hypersensitivity induced by TNBS in rats.

  9. Hypersensitivity reaction studies of a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation.

    PubMed

    Wang, Hongbo; Cheng, Guang; Du, Yuan; Ye, Liang; Chen, Wenzhong; Zhang, Leiming; Wang, Tian; Tian, Jingwei; Fu, Fenghua

    2013-03-01

    The commercial drug paclitaxel (Taxol) may introduce hypersensitivity reactions associated with the polyethoxylated castor oil-ethanol solvent. To overcome these problems, we developed a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation, known as Lipusu. In this study, we performed in vitro and in vivo experiments to compare the safety profiles of Lipusu and Taxol, with special regard to hypersensitivity reactions. First, Swiss mice were used to determine the lethal dosages, and then to evaluate hypersensitivity reactions, followed by histopathological examination and enzyme-linked immunosorbent assays (ELISAs) of serum SC5b-9 and lung histamine. Additionally, healthy human serum was used to analyze in vitro complement activation. Finally, an MTT assay was used to determine the in vitro anti-proliferation activity. Our data clearly showed that Lipusu displayed a much higher safety margin and did not induce hypersensitivity or hypersensitivity-related lung lesions, which may be associated with the fact that Lipusu did not activate complement or increase histamine release in vivo. Moreover, Lipusu did not promote complement activation in healthy human serum in vitro, and demonstrated anti-proliferative activity against human cancer cells, similar to that of Taxol. Therefore, the improved formulation of paclitaxel, which exhibited a much better safety profile and comparable cytotoxic activity to Taxol, may bring a number of benefits to cancer patients.

  10. Comparison of dentine hypersensitivity in selected occidental and oriental populations.

    PubMed

    Gillam, D G; Seo, H S; Newman, H N; Bulman, J S

    2001-01-01

    Epidemiological data on dentine hypersensitivity (DH) prevalence are limited. Few studies have compared prevalence between populations. The aim of this investigation, therefore, was to compare the perception and prevalence of DH in two distinct non-periodontal practice populations, one U.K. and one Korean. Completed questionnaires from 557 patients (230 males and 327 females, comprising 115 males and 162 females, mean age 41.7 years (s.d.=14.36), U.K. and 115 males and 165 females, mean age 29.7 years (s.d.=11.86), Korean) were collected. Analysis was by frequency distribution and cross-tabulation (Statistical Package for the Social Sciences (SPSS)). DH prevalence was similar and at levels comparable with those reported previously. Prevalence was higher in the third and fourth decades in both populations. Although there were no differences between U.K. or Korean males and U.K. or Korean females, there was a significant difference between gender reporting of DH, with more females complaining of DH than males (standard normal deviation (SND)=4.3, 95% confidence interval (CI)=0.1134-0.2736). DH appeared to be regarded by patients as not severe in most cases, so treatment was not generally sought. Of those who claimed to have sought treatment, a significant number had received restorative treatment. Of those patients, only 23.3% of U.K. and or=7 days in either population. The results indicated

  11. Mechanisms of drug hypersensitivity reactions and the skin.

    PubMed

    Kuljanac, Ilko

    2008-01-01

    The skin is an organ most often affected by adverse drug reactions. Because of limited reactivity of the skin, different drugs may induce the same reactions on the skin, even if the same drug may induce different adverse drug reactions. Many of these adverse drug reactions do not include immunological mechanisms, most of them are non-immunological processes. Adverse drug reactions which involve an immune system, may appear different times after drug administration. The severity of reactions is not dependent on the time at which adverse drug reaction appeared, even if some life threatening adverse drug reactions appear immediately after a drug administration. Four types of immunological reactions, (according to Cooms and Gell), may be involved in a drug adverse reaction. The first type of reaction (anaphylactic reaction) begins early after drug administration and different severities of the reactions could exist. The second type, known as cytotoxic hypersensitivity, begins after some minutes to a few hours after a drug administration. Third and fourth types of immunological reactions begin usually hours to days after drug administration. Some types of immunological reactions may begin days to weeks after drug administration. Sensitization to the drugs must be happen early, since re-exposition to the drug leads to the adverse drug reactions. The way of sensitization sometimes determines which immune mechanism will be involved and which clinical reaction will appear. Tests in vivo and in vitro can be used in the diagnosis of adverse drug reactions. All these tests are more or less limited to a false positive or false negative reaction and possibilities of serious reactions in tests. Provocations tests give the most satisfactory results but they may be dangerous and life threatening. We must carefully choose the skin tests and apply them according to the suspected pathomechanism of adverse drug reaction geneses and estimate the usefulness and the risks of the tests

  12. Analysis of deep tissue hypersensitivity to pressure pain in professional pianists with insidious mechanical neck pain

    PubMed Central

    2011-01-01

    Background The aim of this study was to investigate whether pressure pain hyperalgesia is a feature of professional pianists suffering from neck pain as their main playing-related musculoskeletal disorder. Methods Twenty-three active expert pianists, 6 males and 17 females (age: 36 ± 12 years) with insidious neck pain and 23 pianists, 9 males and 14 females (age: 38 ± 10 years) without neck pain the previous year were recruited. A numerical pain rate scale, Neck Disability Index, hand size and pressure pain thresholds (PPT) were assessed bilaterally over the C5-C6 zygapophyseal joint, deltoid muscle, the second metacarpal and the tibialis anterior muscle in a blinded design. Results The results showed that PPT levels were significantly decreased bilaterally over the second metacarpal and tibialis anterior muscles (P < 0.05), but not over C5-C6 zygapophyseal joint and deltoid muscle (P > 0.10), in pianists with neck pain as compared to healthy pianists. Pianists with neck pain had a smaller (P < 0.05) hand size (mean: 181.8 ± 11.8) as compared to pianists without neck pain (mean: 188. 6 ± 13.1). PPT over the tibialis anterior muscles was negatively correlated with the intensity of neck pain. Conclusions Our findings revealed pressure pain hypersensitivity over distant non-symptomatic distant points but not over the symptomatic areas in pianists suffering from neck pain. In addition, pianists with neck pain also had smaller hand size than those without neck pain. Future studies are needed to further determine the relevance of these findings in the clinical course of neck pain as playing-related musculoskeletal disorder in professional pianists. PMID:22111912

  13. Severe Acute Respiratory Syndrome: Clinical Outcome and Prognostic Correlates1

    PubMed Central

    Kwok, Man Leung; Yuen, Hon; Lai, Sik To

    2003-01-01

    Severe acute respiratory syndrome (SARS) poses a major threat to the health of people worldwide. We performed a retrospective case series analysis to assess clinical outcome and identify pretreatment prognostic correlates of SARS, managed under a standardized treatment protocol. We studied 127 male and 196 female patients with a mean age of 41±14 (range 18–83). All patients, except two, received ribavirin and steroid combination therapy. In 115 (36%) patients, the course of disease was limited. Pneumonitis progressed rapidly in the remaining patients. Sixty-seven (21%) patients required intensive care, and 42 (13%) required ventilator support. Advanced age, high admission neutrophil count, and high initial lactate dehydrogenase level were independent correlates of an adverse clinical outcome. SARS-associated coronavirus caused severe illnesses in most patients, despite early treatment with ribavirin and steroid. This study has identified three independent pretreatment prognostic correlates. PMID:14519241

  14. Evaluation of Dentifrice Containing Nano-hydroxyapatite for Dentinal Hypersensitivity: A Randomized Controlled Trial

    PubMed Central

    Gopinath, Nithin Manchery; John, Joseph; Nagappan, N; Prabhu, S; Kumar, E Senthil

    2015-01-01

    Background: This randomized, double-blind, parallel arm study was carried out to evaluate and compare the effectiveness between nano-hydroxyapatite (HAP) and a benchmark dentifrice in reducing dentin hypersensitivity. Materials and Methods: About 36 patients were selected, randomly divided into two groups and was evaluated clinically using three different stimuli, i.e., tactile, air blast, and cold water test. The patient’s responses to various stimuli were recorded using a visual analog scale at baseline and after 4 weeks. Results: Statistical analysis was done using unpaired and paired t-tests. It was seen that patients treated in both groups showed significant reductions scores across all sensitivity measures at the end of 4 weeks. Conclusion: The HAP containing toothpaste was effective in reducing dentin hypersensitivity with pre-existing benchmark toothpaste tested and hence can be advocated in the management of hypersensitivity. PMID:26464553

  15. Hypersensitivity myocarditis confirmed by cardiac magnetic resonance imaging and endomyocardial biopsy.

    PubMed

    Park, Yumi; Ahn, Sung Gyun; Ko, Anna; Ra, Sang Ho; Cha, Jaehwang; Jee, Yong Gwan; Lee, Ji Hyun

    2014-03-01

    Myocarditis often occurs due to viral infections and postviral immune-mediated responses. Hypersensitivity myocarditis is a rare form of myocarditis. Numerous drugs can induce myocarditis, which is typically reversible after withdrawal of the causative agent. Here, we report a case of hypersensitivity myocarditis that was probably triggered by amoxicillin and that resolved completely with heart failure management as well as discontinuation of the drug. A 68-year-old woman presented with acute chest pain mimicking acute coronary syndromes, but the coronary angiography was normal. A recent history of taking medications, skin rash, and peripheral eosinophilia suggested a diagnosis of hypersensitivity myocarditis, which was confirmed by cardiac magnetic resonance imaging and endomyocardial biopsy.

  16. Carbamazepine-induced anticonvulsant hypersensitivity syndrome--pathogenic and diagnostic considerations.

    PubMed

    Scerri, L; Shall, L; Zaki, I

    1993-11-01

    Two epileptic patients developed an infectious mononucleosis-like illness which subsequently proved to be a carbamazepine-induced anticonvulsant hypersensitivity syndrome. Patch testing to carbamazepine 3 years later was positive in the one patient tested and negative in normal controls. The second patient died a few weeks after the illness, secondary to long-standing cardiac disease without having undergone patch testing. A skin biopsy was, however, consistent with an immune complex mediated drug reaction. Patch testing for systemically administered drugs is generally believed to be of little value in diagnosing drug allergies. However, we reinforce a previous suggestion that this investigation may be helpful in some cases of anticonvulsant hypersensitivity syndrome caused by carbamazepine. The pathogenic role of type 3 and 4 hypersensitivity is also discussed.

  17. Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity

    PubMed Central

    Yin, Shijin; Luo, Jialie; Qian, Aihua; Du, Junhui; Yang, Qing; Zhou, Shentai; Yu, Weihua; Du, Guangwei; Clark, Richard B.; Walters, Edgar T.; Carlton, Susan M.; Hu, Hongzhen

    2013-01-01

    Retinoids are structurally related derivatives of vitamin A and are required for normal vision as well as cell proliferation and differentiation. Clinically, retinoids are effective in treating many skin disorders and cancers. Application of retinoids evokes substantial irritating side effects, including pain and inflammation; however, the precise mechanisms accounting for the sensory hypersensitivity are not understood. Here we show that both naturally occurring and synthetic retinoids activate recombinant or native transient receptor potential channel vanilloid subtype 1 (TRPV1), an irritant receptor for capsaicin, the pungent ingredient of chili peppers. In vivo, retinoids produced pain-related behaviors that were either eliminated or significantly reduced by genetic or pharmacological inhibition of TRPV1 function. These findings identify TRPV1 as an ionotropic receptor for retinoids and provide cellular and molecular insights into retinoid-evoked hypersensitivity. These findings also suggest that selective TRPV1 antagonists are potential therapeutic drugs for treating retinoid-induced sensory hypersensitivity. PMID:23925292

  18. Sensory Hypersensitivity Predicts Reduced Sleeping Quality in Patients With Major Affective Disorders.

    PubMed

    Engel-Yeger, Batya; Gonda, Xenia; Walker, Muffy; Rihmer, Zoltan; Pompili, Maurizio; Amore, Mario; Serafini, Gianluca

    2017-01-01

    The goal of this study was to examine the sensory profile (expressed as hypersensitivity or hyposensitivity) of patients with major affective disorders and its relative contribution to the prediction of sleep quality while considering affective temperaments and depression, which may impact sleep quality. We recruited 176 participants (mean age, 47.3 y), of whom 56.8% had a diagnosis of unipolar major depressive disorder and 43.2% a diagnosis of bipolar disorder. Reduced sleep quality was evaluated using the Pittsburgh Sleep Quality Index. Affective temperaments were assessed using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego. Sensory hypersensitivity, assessed using the Adolescent/Adult Sensory Profile, significantly distinguished between poor and good sleepers. Sleep quality was mainly predicted by the Beck Depression Inventory-II total score and anxious temperament. Sensory hypersensitivity contributed to this prediction mainly with regard to sleep efficiency and related daytime dysfunction.

  19. Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity.

    PubMed

    Yin, Shijin; Luo, Jialie; Qian, Aihua; Du, Junhui; Yang, Qing; Zhou, Shentai; Yu, Weihua; Du, Guangwei; Clark, Richard B; Walters, Edgar T; Carlton, Susan M; Hu, Hongzhen

    2013-09-01

    Retinoids are structurally related derivatives of vitamin A and are required for normal vision as well as cell proliferation and differentiation. Clinically, retinoids are effective in treating many skin disorders and cancers. Application of retinoids evokes substantial irritating side effects, including pain and inflammation; however, the precise mechanisms accounting for the sensory hypersensitivity are not understood. Here we show that both naturally occurring and synthetic retinoids activate recombinant or native transient receptor potential channel vanilloid subtype 1 (TRPV1), an irritant receptor for capsaicin, the pungent ingredient of chili peppers. In vivo, retinoids produced pain-related behaviors that were either eliminated or significantly reduced by genetic or pharmacological inhibition of TRPV1 function. These findings identify TRPV1 as an ionotropic receptor for retinoids and provide cellular and molecular insights into retinoid-evoked hypersensitivity. These findings also suggest that selective TRPV1 antagonists are potential therapeutic drugs for treating retinoid-induced sensory hypersensitivity.

  20. Aminophylline suppresses stress-induced visceral hypersensitivity and defecation in irritable bowel syndrome

    PubMed Central

    Asano, Teita; Tanaka, Ken-ichiro; Tada, Arisa; Shimamura, Hikaru; Tanaka, Rikako; Maruoka, Hiroki; Takenaga, Mitsuko; Mizushima, Tohru

    2017-01-01

    Pharmacological therapy for irritable bowel syndrome (IBS) has not been established. In order to find candidate drugs for IBS with diarrhea (IBS-D), we screened a compound library of drugs clinically used for their ability to prevent stress-induced defecation and visceral hypersensitivity in rats. We selected the bronchodilator aminophylline from this library. Using a specific inhibitor for each subtype of adenosine receptors (ARs) and phosphodiesterases (PDEs), we found that both A2BARs and PDE4 are probably mediated the inhibitory effect of aminophylline on wrap restraint stress (WRS)-induced defecation. Aminophylline suppressed maternal separation- and acetic acid administration-induced visceral hypersensitivity to colorectal distension (CRD), which was mediated by both A2AARs and A2BARs. We propose that aminophylline is a candidate drug for IBS-D because of its efficacy in both of stress-induced defecation and visceral hypersensitivity, as we observed here, and because it is clinically safe. PMID:28054654

  1. Drug hypersensitivity in human immunodeficiency virus-infected patient: challenging diagnosis and management

    PubMed Central

    Widhani, Alvina; Karjadi, Teguh Harjono

    2014-01-01

    Human immunodeficiency virus (HIV)-infected patients present complex immunological alterations. Multiple drugs that usually prescribed for prevention or treatment of opportunistic infections and antiretroviral pose these patients a higher risk of developing drug hypersensitivity. All antiretroviral agents and drugs to treat opportunistic infections have been reported to cause drug hypersensitivity reactions. Allergic reactions with antiretroviral are not restricted to older agents, although newer drugs usually more tolerated. Cutaneous adverse drug reactions are the most common manifestation of drug hypersensitivity in HIV, typically manifesting as maculopapular rash with or without systemic symptoms in the presence or absence of internal organ involvement. The onset of an allergic reaction is usually delayed. Severe drug hypersensitity reactions as erythema multiforme, Stevens Johnson syndrome and toxic epidermal necrolysis develop more often in HIV-infected patients compared to other populations. Mild to moderate rash without systemic symptom or organ involvement usually do not need drug discontinuation. Appropriate diagnosis and management of drug hypersensitivity reactions are essential, especially in patients with very low CD4+ T-cell count and multiple opportunistic infections. Clinicians should aware of different half-life of each drug when decided to stop the drug. Knowledge of the metabolism, recognition of the risk factors, and the ability to suggest the probability of particular drug as causative are also important points. A step wise rechallenge test or desensitization with the offending drug might be a preferable action and more commonly used in managing drug hypersensitivity in HIV-infected patients. Desensitization protocols have been successfully done for several antiretroviral and opportunistic infection drugs. PMID:24527412

  2. Adrenergic β2-receptors mediates visceral hypersensitivity induced by heterotypic intermittent stress in rats.

    PubMed

    Zhang, Chunhua; Rui, Yun-Yun; Zhou, Yuan-Yuan; Ju, Zhong; Zhang, Hong-Hong; Hu, Chuang-Ying; Xiao, Ying; Xu, Guang-Yin

    2014-01-01

    Chronic visceral pain in patients with irritable bowel syndrome (IBS) has been difficult to treat effectively partially because its pathophysiology is not fully understood. Recent studies show that norepinephrine (NE) plays an important role in the development of visceral hypersensitivity. In this study, we designed to investigate the role of adrenergic signaling in visceral hypersensitivity induced by heterotypical intermittent stress (HIS). Abdominal withdrawal reflex scores (AWRs) used as visceral sensitivity were determined by measuring the visceromoter responses to colorectal distension. Colon-specific dorsal root ganglia neurons (DRGs) were labeled by injection of DiI into the colon wall and were acutely dissociated for whole-cell patch-clamp recordings. Blood plasma level of NE was measured using radioimmunoassay kits. The expression of β2-adrenoceptors was measured by western blotting. We showed that HIS-induced visceral hypersensitivity was attenuated by systemic administration of a β-adrenoceptor antagonist propranolol, in a dose-dependent manner, but not by a α-adrenoceptor antagonist phentolamine. Using specific β-adrenoceptor antagonists, HIS-induced visceral hypersensitivity was alleviated by β2 adrenoceptor antagonist but not by β1- or β3-adrenoceptor antagonist. Administration of a selective β2-adrenoceptor antagonist also normalized hyperexcitability of colon-innervating DRG neurons of HIS rats. Furthermore, administration of β-adrenoceptor antagonist suppressed sustained potassium current density (IK) without any alteration of fast-inactivating potassium current density (IA). Conversely, administration of NE enhanced the neuronal excitability and produced visceral hypersensitivity in healthy control rats, and blocked by β2-adrenoceptor antagonists. In addition, HIS significantly enhanced the NE concentration in the blood plasma but did not change the expression of β2-adrenoceptor in DRGs and the muscularis externa of the colon. The

  3. Fanconi anemia complementation group A cells are hypersensitive to chromium(VI)-induced toxicity.

    PubMed Central

    Vilcheck, Susan K; O'Brien, Travis J; Pritchard, Daryl E; Ha, Linan; Ceryak, Susan; Fornsaglio, Jamie L; Patierno, Steven R

    2002-01-01

    Fanconi anemia (FA) is an autosomal recessive disorder characterized by diverse developmental abnormalities, progressive bone marrow failure, and a markedly increased incidence of malignancy. FA cells are hypersensitive to DNA cross-linking agents, suggesting a general defect in the repair of DNA cross-links. Some forms of hexavalent chromium [Cr(VI)] are implicated as respiratory carcinogens and induce several types of DNA lesions, including ternary DNA-Cr-DNA interstrand cross-links (Cr-DDC). We hypothesized that human FA complementation group A (FA-A) cells would be hypersensitive to Cr(VI) and Cr(VI)-induced apoptosis. Using phosphatidylserine translocation and caspase-3 activation, human FA-A fibroblasts were found to be markedly hypersensitive to chromium-induced apoptosis compared with CRL-1634 cells, which are normal human foreskin fibroblasts (CRL). The clonogenicity of FA-A cells was also significantly decreased compared with CRL cells after Cr(VI) treatment. There was no significant difference in either Cr(VI) uptake or Cr-DNA adduct formation between FA-A and CRL cells. These results show that FA-A cells are hypersensitive to Cr(VI) and Cr-induced apoptosis and that this hypersensitivity is not due to increased Cr(VI) uptake or increased Cr-DNA adduct formation. The results also suggest that Cr-DDC may be proapoptotic lesions. These results are the first to show that FA cells are hypersensitive to an environmentally relevant DNA cross-linking agent. PMID:12426130

  4. Abolishment of TNBS-induced visceral hypersensitivity in mast cell deficient rats.

    PubMed

    Ohashi, Katsuyo; Sato, Yasushi; Kawai, Mitsuhisa; Kurebayashi, Yoichi

    2008-02-13

    Mucosal mast cells are implicated in visceral hypersensitivity associated with irritable bowel syndrome (IBS). In this study, we investigated the role of mast cells in the development of visceral hypersensitivity by using mast cell deficient (Ws/Ws) rats and their control (W+/W+). In W+/W+ rats, an injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the proximal colon produced a significant decrease in pain threshold of the distal colon. Severe mucosal necrosis and inflammatory cell infiltration with concomitant increase in tissue myeloperoxidase activity were observed in the proximal colon that was directly insulted by TNBS, whereas neither necrosis nor increased myeloperoxidase activity occurred in the distal colon, indicating that TNBS-induced hypersensitivity is not caused by the local tissue damage or inflammation in the region of the gut where distention stimuli were applied. On the other hand, TNBS failed to elicit visceral hypersensitivity in Ws/Ws rats. This finding indicates that mast cells are essential for development of TNBS-induced visceral hypersensitivity in rats. Since the severity of TNBS-induced proximal colon injury and MPO activity was not affected by mast cell deficiency, it is unlikely that abolishment of visceral hypersensitivity in mast cell deficient rats was a result of altered development of the primary injury in the proximal colon. There was no difference between sham-operated Ws/Ws and W+/W+ rats in colonic pain threshold to distention stimuli, indicating that mast cells play no modulatory roles in normal colonic nociception. The present results support the view that mucosal mast cells play key roles in the pathogenesis of IBS.

  5. Phenotypic analysis of pulmonary perivascular mononuclear infiltrates that occur as a direct result of acute lethal graft-versus-host disease describes the onset of interstitial pneumonitis.

    PubMed Central

    Workman, D. L.; Clancy, J.

    1995-01-01

    We recently determined that the sequential development of interstitial pneumonitis and lymphocytic bronchiolitis/bronchitis occurs as a direct result of acute lethal graft-versus-host disease. Interstitial pneumonitis develops before lymphocytic bronchiolitis/bronchitis primarily from the dissemination of perivascular mononuclear infiltrates. We have used the adult, nonirradiated (DA x LEW) F1 hybrid rat in the absence of chemotherapy, immunosuppression, or overt infection to determine the phenotype of infiltrating perivascular mononuclear cells throughout acute lethal graft-versus-host disease. F1 animals were intravenously injected with 1 x 10(6) DA parental lymphoid cells/g body weight, which produced 100% morbidity and mortality by day 21. Graft-versus-host disease animals were killed on days 3, 7, 10, 14, and 15 to 21 after injection. Whole left lung lobes were frozen, serially sectioned (4 microns), and incubated with a panel of mouse anti-rat monoclonal antibodies. Labeled antibody density was determined by computerized image analysis. Perivascular infiltration was observed first for ED1+, OX8+, and W3/25+ cells, and then OX41+, W3/13+ and OX19/25+ populations. OX6 was expressed in control tissues and at all time points tested. OX12+, OX39+ and MOM/3F12/F2+ cells were not quantifiable. The present study has determined that the process of perivascular infiltration was produced through a biphasic influx of OX6+, T-cell, and macrophage populations. Images Figure 1 Figure 4 PMID:7485398

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

    PubMed Central

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

    2014-01-01

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

  7. Pneumonitis and Multi-Organ System Disease in Common Marmosets (Callithrix jacchus) Infected with the Severe Acute Respiratory Syndrome-Associated Coronavirus

    PubMed Central

    Greenough, Thomas C.; Carville, Angela; Coderre, James; Somasundaran, Mohan; Sullivan, John L.; Luzuriaga, Katherine; Mansfield, Keith

    2005-01-01

    Severe acute respiratory syndrome (SARS) is a significant emerging infectious disease. Humans infected with the etiological agent, SARS-associated coronavirus (SARS-CoV), primarily present with pneumonitis but may also develop hepatic, gastrointestinal, and renal pathology. We inoculated common marmosets (Callithrix jacchus) with the objective of developing a small nonhuman primate model of SARS. Two groups of C. jacchus were inoculated intratracheally with cell culture supernatant containing SARS-CoV. In a time course pathogenesis study, animals were evaluated at 2, 4, and 7 days after infection for morphological changes and evidence of viral replication. All animals developed a multifocal mononuclear cell interstitial pneumonitis, accompanied by multinucleated syncytial cells, edema, and bronchiolitis in most animals. Viral antigen localized primarily to infected alveolar macrophages and type-1 pneumocytes by immunohistochemistry. Viral RNA was detected in all animals from pulmonary tissue extracts obtained at necropsy. Viral RNA was also detected in tracheobronchial lymph node and myocardium, together with inflammatory changes, in some animals. Hepatic inflammation was observed in most animals, predominantly as a multifocal lymphocytic hepatitis accompanied by necrosis of individual hepatocytes. These findings identify the common marmoset as a promising nonhuman primate to study SARS-CoV pathogenesis. PMID:16049331

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

    PubMed

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

    2014-07-01

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

  9. Immediate hypersensitivity reaction following liposomal amphotericin-B (AmBisome) infusion.

    PubMed

    Nath, Proggananda; Basher, Ariful; Harada, Michiyo; Sarkar, Santana; Selim, Shahjada; Maude, Richard J; Noiri, Eisei; Faiz, Abul

    2014-10-01

    Liposomal amphotericin-B (AmBisome) is now becoming first choice for the treatment of visceral leishmaniasis (kala-azar) patients due to high efficacy and less toxicity. The reported incidence of hypersensitivity reactions to liposomal amphotericin-B (AmBisome), especially during therapy, is very rare. We report two patients with kala-azar: one developed breathing difficulties and hypotension followed by shock and the other had facial angioedema with chest tightness during treatment. Both patients were managed with immediate action of injection: adrenaline, diphenhydramine and hydrocortisone. In our experience, AmBisome can cause severe hypersensitivity reactions that warrant proper support and close supervision.

  10. Visceral hypersensitivity and electromechanical dysfunction as therapeutic targets in pediatric functional dyspepsia

    PubMed Central

    Rosen, John M; Cocjin, Jose T; Schurman, Jennifer V; Colombo, Jennifer M; Friesen, Craig A

    2014-01-01

    Functional gastrointestinal disorders (FGID) are common clinical syndromes diagnosed in the absence of biochemical, structural, or metabolic abnormalities. They account for significant morbidity and health care expenditures and are identifiable across variable age, geography, and culture. Etiology of abdominal pain associated FGIDs, including functional dyspepsia (FD), remains incompletely understood, but growing evidence implicates the importance of visceral hypersensitivity and electromechanical dysfunction. This manuscript explores data supporting the role of visceral hypersensitivity and electromechanical dysfunction in FD, with focus on pediatric data when available, and provides a summary of potential therapeutic targets. PMID:25133041

  11. Antibiotic hypersensitivity in CF: drug-induced life-threatening hemolytic anemia in a pediatric patient.

    PubMed

    Chavez, Alma; Mian, Amir; Scurlock, Amy M; Blackall, Douglas; Com, Gulnur

    2010-12-01

    Adverse reactions to antibiotics in patients with cystic fibrosis (CF) are a growing concern. We report the case of a pediatric patient with CF with multiple comorbidities and a history of drug reactions, who developed life-threatening piperacillin-induced immune hemolytic anemia. We review drug-induced hemolytic anemia (DIIHA) in particular, and antibiotic hypersensitivity in CF in general, including the frequency, pathogenesis, and risk factors. Finally, we discuss the treatment options and propose an algorithm for the management of drug-induced hypersensitivity reactions in patients with CF.

  12. Hypersensitivity to molybdenum as a possible trigger of ANA-negative systemic lupus erythematosus.

    PubMed Central

    Federmann, M; Morell, B; Graetz, G; Wyss, M; Elsner, P; von Thiessen, R; Wüthrich, B; Grob, D

    1994-01-01

    After implantation of two metal plates a 24 year old woman developed fever of unknown origin and successively more symptoms of an ANA-negative systemic lupus erythematosus (SLE). These symptoms resolved after removal of the plates and recurred during patch testing of the metal components, which showed a reaction to molybdenum. A lymphocyte transformation test indicated a delayed-type hypersensitivity to molybdenum. Subsequent progressive flare ups of SLE appeared without molybdenum reexposure. This is the first report suggesting the existence of a hypersensitivity to molybdenum, which may act as another environmental trigger for SLE. PMID:8037499

  13. Hypersensitivity to aspirin and urgent percutaneous coronary intervention: A therapeutic challenge.

    PubMed

    Duarte, Tatiana; Gonçalves, Sara; Sá, Catarina; Marinheiro, Rita; Rodrigues, Rita; Seixo, Filipe; Tomas, Elza; Caria, Rui

    2016-11-01

    Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs are common and five types of reactions have been defined. The prevalence of such reactions in patients with myocardial infarction is unclear, and so antiplatelet therapy in this population is a challenge. Various desensitization protocols have been developed but there are no specific guidelines for their use. The authors present the case of a patient with acute coronary syndrome and aspirin hypersensitivity referred for urgent coronary angiography. Aspirin desensitization therapy is safe and successful in many patients, but more randomized trials are needed to confirm its benefits in coronary artery disease patients.

  14. Immediate hypersensitivity to penicillins with negative skin tests--the value of specific IgE.

    PubMed

    Silva, R; Cruz, L; Botelho, C; Castro, E; Cadinha, S; Castel-Branco, M G; Rodrigues, J

    2009-08-01

    The determination of specific IgE in patients with history of penicillins hypersensitivity is simple, safe and widely available. The positive and negative predictive values of this determination, however, are not yet established. In order to evaluate them, we performed specific IgE determination and diagnostic drug challenges in a group of 22 patients with a clear history of immediate penicillins hypersensitivity but negative skin tests. In this sample, the positive and negative predictive values were 29% and 87%, respectively. This seems to indicate that a positive specific IgE is not enough to confirm the diagnosis, and further study is necessary.

  15. Cracking the shell on egg-hypersensitive patients and egg-containing vaccines.

    PubMed

    Chernin, Leah R; Swender, David; Hostoffer, Robert W

    2011-10-01

    Hens' eggs are a common food in the American diet. They are consumed as a primary food source and added as an ingredient to other foods. In individuals who are hypersensitive to eggs, egg-containing foods can cause mild to severe allergic reactions if ingested. These individuals may also have adverse reactions to vaccines produced on egg media. Vaccines that are created on egg media include those for measles, mumps, and rubella; rabies; yellow fever; and influenza. The authors discuss recent developments in the use of egg-containing vaccines in hypersensitive patients.

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

    SciTech Connect

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

    2014-02-01

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

  17. LcrV delivered via type III secretion system of live attenuated Yersinia pseudotuberculosis enhances immunogenicity against pneumonic plague.

    PubMed

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

    2014-10-01

    Here, we constructed a Yersinia pseudotuberculosis mutant strain with arabinose-dependent regulated and delayed shutoff of crp expression (araC P(BAD) crp) and replacement of the msbB gene with the Escherichia coli msbB gene to attenuate it. Then, we inserted the asd mutation into this construction to form χ10057 [Δasd-206 ΔmsbB868::P(msbB) msbB(EC) ΔP(crp21)::TT araC P(BAD) crp] for use with a balanced-lethal Asd-positive (Asd(+)) plasmid to facilitate antigen synthesis. A hybrid protein composed of YopE (amino acids [aa]1 to 138) fused with full-length LcrV (YopE(Nt138)-LcrV) was synthesized in χ10057 harboring an Asd(+) plasmid (pYA5199, yopE(Nt138)-lcrV) and could be secreted through a type III secretion system (T3SS) in vitro and in vivo. Animal studies indicated that mice orally immunized with χ10057(pYA5199) developed titers of IgG response to whole-cell lysates of Y. pestis (YpL) and subunit LcrV similar to those seen with χ10057(pYA3332) (χ10057 plus an empty plasmid). However, only immunization of mice with χ10057(pYA5199) resulted in a significant secretory IgA response to LcrV. χ10057(pYA5199) induced a higher level of protection (80% survival) against intranasal (i.n.) challenge with ~240 median lethal doses (LD50) (2.4 × 10(4) CFU) of Y. pestis KIM6+(pCD1Ap) than χ10057(pYA3332) (40% survival). Splenocytes from mice vaccinated with χ10057(pYA5199) produced significant levels of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-17 (IL-17) after restimulation with LcrV and YpL antigens. Our results suggest that it is possible to use an attenuated Y. pseudotuberculosis strain delivering the LcrV antigen via the T3SS as a potential vaccine candidate against pneumonic plague.

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

    SciTech Connect

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

    2015-05-01

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

  19. Evidence for reactivation of human herpesvirus 6 in generalized lymphadenopathy in a patient with drug-induced hypersensitivity syndrome.

    PubMed

    Saraya, Takeshi; Mikoshiba, Michiaki; Kamiyama, Harumi; Yoshizumi, Masakazu; Tsuchida, Shigeru; Tsukagoshi, Hiroyuki; Ishioka, Taisei; Terada, Miho; Tanabe, Eiichi; Tomioka, Chizuko; Ishii, Haruyuki; Kimura, Hirokazu; Kozawa, Kunihisa; Shiohara, Tetsuo; Takizawa, Hajime; Goto, Hajime

    2013-06-01

    The present case provides direct evidence of human herpesvirus 6 reactivation in resected lymph node tissue in a patient with drug-induced hypersensitivity syndrome. This case clearly demonstrates that appropriate pathological evaluation of lymphadenopathy for drug-induced hypersensitivity syndrome, which mimics malignant lymphoma in clinical, radiological, and pathological findings, is required.

  20. Zirconium granuloma resulting from an aluminum zirconium complex: a previously unrecognized agent in the development of hypersensitivity granulomas.

    PubMed

    Skelton, H G; Smith, K J; Johnson, F B; Cooper, C R; Tyler, W F; Lupton, G P

    1993-05-01

    Zirconium compounds have been associated with the development of hypersensitivity granulomas. However, aluminum zirconium complexes have not previously been shown to induce sensitization. We present the clinical and histologic findings of a case in which a patient developed an acute hypersensitivity reaction to an aluminum zirconium complex.

  1. Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients.

    PubMed

    Ben m'rad, Mona; Leclerc-Mercier, Stéphanie; Blanche, Philippe; Franck, Nathalie; Rozenberg, Flore; Fulla, Yvonne; Guesmi, Myriam; Rollot, Florence; Dehoux, Monique; Guillevin, Loïc; Moachon, Laurence

    2009-05-01

    ) levels in 18 patients and found that 9 patients had vitamin D deficiency (<25 nmol/L or <10 microg/L) and 5 had vitamin D insufficiency (25-50 nmol/L). Moreover, 25(OH)D3 levels were inversely correlated with ferritin values. After culprit-drug withdrawal, outcomes were favorable for all patients, including those with cardiac abnormalities under slow tapering of glucocorticoids.We recommend looking for the frequent but underdiagnosed hypersensitivity myocarditis with noninvasive diagnostic tools, such as N-terminal probrain natriuretic peptide, and promptly withdrawing the culprit drug and starting glucocorticoids. Vitamin D deficiency might be a DIHS risk or severity factor, especially for patients with high skin phototype and during the winter. Because DIHS clinical and laboratory patterns share similarities with AOSD and hemophagocytosis, DIHS should be included in their differential diagnoses.

  2. Seasonal differences in cytokine expression in the skin of Shetland ponies suffering from insect bite hypersensitivity.

    PubMed

    Meulenbroeks, C; van der Meide, N M A; Zaiss, D M W; van Oldruitenborgh-Oosterbaan, M M Sloet; van der Lugt, J J; Smak, J; Rutten, V P M G; Willemse, T

    2013-01-15

    Insect bite hypersensitivity (IBH) in horses is a seasonal, IgE-mediated, pruritic skin disorder primarily caused by Culicoides spp. We hypothesize that a mixed Th2/Th1-type immune status, off season, alters into Th2-dominated immune reactivity in the skin of IBH-affected ponies in the IBH season. To study these immune response patterns Culicoides-specific IgE levels, skin histopathology and cytokine and transcription factor mRNA expression (IL4, IL10, IL13, IFNγ, FoxP3 and CD3(ζ)) in lesional and non-lesional skin of ponies affected by IBH in the IBH season were compared with those of the same animals off season and those in skin of healthy ponies in both seasons. The present study revealed a significantly higher histopathology score in lesional skin of affected ponies than in non-lesional skin and skin of healthy ponies in the IBH season. Culicoides obsoletus-specific IgE serum levels of ponies with IBH were significantly higher than those in healthy ponies in both seasons. Interestingly, C. obsoletus-specific IgE serum levels within each group were the same in the IBH season and off season. The expression of IL4, IL13 and IFNγ mRNA in skin biopsies in the IBH season showed a significant increase compared to off season in both skin derived from healthy control ponies (n=14) as well as in lesional and in non-lesional skin from IBH-affected animals (n=17). This apparently general up-regulation of cytokine expression during the IBH season directly correlated with an increased CD3(ζ) mRNA expression in the skin, indicating an overall increased T cell influx during the summer months. The only significant difference observed between lesional skin from IBH-affected animals as compared to skin from healthy control animals in the IBH season was a lower expression of IL13/CD3(ζ) in the affected animals. FoxP3 and IL10 levels were unaffected, except for a lower expression of FoxP3 in healthy control skin in the IBH season as compared to off season, In addition, the

  3. Correlations between edema and the immediate and prolonged painful consequences of inflammation: therapeutic implications?

    SciTech Connect

    Chesler, Elissa J; Lariviere, William R; Zhen, Li; Shang, G; Chen, Ya; Yu, Yao; Lu, Zhuo; Chang, Ying; Luo, Ceng; Li, KaiCheng; Chen, Jun

    2005-06-01

    The precise relationship between the degree of pan and the degree of inflammation in the individual remains debated. A quantitative analysis simultaneously applied to the immediate and prolonged painful consequences of inflammation has not yet been done. Thus, the correlations between edema, nociception and hypersensitivity following an inflammatory insult were assessed in rodents. To better understand the therapeutic value of modifying specific aspects of inflammation, the effects of anti-inflammatory drug were compared to the results. Inbred strains of mice and outbred rats received an intraplantar injection of honeybee venom and the between group and within-group correlations were calculated for spontaneous nociceptive measures, thermal and mechanical hypersensitivity, and edema and temperature. The effect of indomethacin on the pain and the inflammation measures was examined. Edema correlated with spontaneous flinching, licking and lifting of the inject paw, and not with thermal or mechanical hypersensitivity. Indomethacin affected edema and spontaneous nociception dose-dependently, and affected hypersensitivity only at the highest dose test (P <0.005). These results suggest that edema may contribute only to immediate spontaneous nociceptive responses to an inflammatory insult, and not to the more clinically relevant prolonged hypersensitivity. This analysis represents a method for determine which inflammatory processes are the most promising therapeutic targets against the multiple painful consequences of inflammation.

  4. Proliferation of the synovial lining cell layer in suggested metal hypersensitivity.

    PubMed

    Burkandt, Andreas; Katzer, Alexander; Thaler, Karlheinz; Von Baehr, Volker; Friedrich, Reinhard E; Rüther, Wolfgang; Amling, Michael; Zustin, Jozef

    2011-01-01

    Synovial tissues in joints with prostheses display characteristic morphological changes in cases with aseptic failure, particularly macrophage infiltration. Since proliferation of the synovial lining cell layer represents a feature characteristic of autoimmune joint diseases, the possibility of morphological changes of the synovial lining cell layer in periprosthetic tissues was investigated. Synovial biopsies from five groups of morphologically well-defined lesions (osteoarthritis, rheumatoid arthritis, aseptic loosened metal-on-polyethylene and metal-on-metal arthroplasty and suggested metal hypersensitivity) were compared using a conventional staining method and immunohistochemistry. The synovial lining cell layer was substantially enlarged in both rheumatoid arthritis and cases suggestive of metal hypersensitivity. Macrophage infiltrates were apparent in rheumatoid arthritis and all specimens from retrieved hip arthroplasties. Although both synovial and subsynovial macrophages were positive for CD163 (indicating synovial M2 macrophages), the remaining fibroblast-like synoviocytes and scattered stromal fibroblasts showed a positive reaction with the D2-40 antibody (indicating fibroblast-like synoviocytes). Furthermore, in contrast to CD163-positive macrophages, the enlarged D2-40-positive fibroblast-like synoviocytes displayed cytoplasmatic tubular projections. Proliferation of the periprosthetic synovial lining cell layer occurred in cases with unexplained groin pain following metal-on-metal hip resurfacing arthroplasty, suggestive of hypersensitivity. Despite some important study limitations, the present observation adds to the evidence that metal hypersensitivity shares characteristic morphological features with autoimmune diseases of the joints.

  5. New Allergic and Hypersensitivity Conditions Section in the International Classification of Diseases-11.

    PubMed

    Tanno, Luciana K; Calderon, Moises A; Demoly, Pascal

    2016-07-01

    Allergy and hypersensitivity, originally perceived as rare and secondary disorders, are one of the fastest growing conditions worldwide, but not adequately tracked in international information systems, such as the International Classification of Diseases (ICD). Having allergic and hypersensitivity conditions classification able to capture conditions in health international information systems in a realistic manner is crucial to the identification of potential problems, and in a wider system, can identify contextually specific service deficiencies and provide the impetus for changes. Since 2013, an international collaboration of Allergy Academies has spent tremendous efforts to have a better and updated classification of allergies in the forthcoming International Classification of Diseases (ICD)-11 version, by providing scientific and technical evidences for the need for changes. The following bilateral discussions with the representatives of the ICD-11 revision, a simplification process was carried out. The new parented "Allergic and hypersensitivity conditions" section has been built under the "Disorders of the Immune System" chapter through the international collaboration of Allergy Academies and upon ICD WHO representatives support. The classification of allergic and hypersensitivity conditions has been updated through the ICD-11 revision and will allow the aggregation of reliable data to perform positive quality-improvements in health care systems worldwide.

  6. Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1/CCR3 blockade

    PubMed Central

    Nakamura, Takao; Ohbayashi, Masaharu; Kuo, Chuan Hui; Komatsu, Naoki; Yakura, Keiko; Tominaga, Takeshi; Inoue, Yoshitsugu; Higashi, Hidemitsu; Murata, Meguru; Takeda, Shuzo; Fukushima, Atsuki; Liu, Fu-Tong; Rothenberg, Marc E.; Ono, Santa Jeremy

    2009-01-01

    The immune response is regulated, in part, by effector cells whose activation requires multiple signals. For example, T cells require signals emanating from the T cell antigen receptor and co-stimulatory molecules for full activation. Here, we present evidence indicating that IgE-mediated hypersensitivity reactions in vivo also require cognate signals to activate mast cells. Immediate hypersensitivity reactions in the conjunctiva are ablated in mice deficient in eotaxin-1, despite normal numbers of tissue mast cells and levels of IgE. To further define the co-stimulatory signals mediated by chemokine receptor 3 (CCR3), an eotaxin-1 receptor, effects of CCR3 blockade were tested with an allergic conjunctivitis model and in ex vivo isolated connective tissue-type mast cells. Our results show that CCR3 blockade significantly suppresses allergen-mediated hypersensitivity reactions as well as IgE-mediated mast cell degranulation. We propose that a co-stimulatory axis by CCR3, mainly stimulated by eotaxin-1, is pivotal in mast cell-mediated hypersensitivity reactions. PMID:19147836

  7. Transient Receptor Potential Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades Underlying Visceral Hypersensitivity.

    PubMed

    Balemans, Dafne; Boeckxstaens, Guy E; Talavera, Karel; Wouters, Mira M

    2017-04-06

    Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders (FGID) including functional dyspepsia, irritable bowel syndrome (IBS) and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family. A variety of TRP channels are present in the gastrointestinal tract (TRPV1, TRPV3, TRPV4, TRPA1, TRPM2, TRPM5 and TRPM8) and modulation of their function by increased activation or sensitization (decreased activation threshold) or altered expression in visceral afferents, have been reported in visceral hypersensitivity. TRP channels directly detect or transduce osmotic, mechanical, thermal and chemosensory stimuli. In addition, pro-inflammatory mediators released in tissue damage or inflammation can activate receptors of the G-protein coupled receptor (GPCR) superfamily leading to TRP channel sensitization and activation, which amplify pain and neurogenic inflammation. In this review, we highlight the current knowledge on the functional roles of neuronal TRP channels in visceral hypersensitivity and discuss the signaling pathways that underlie TRP channel modulation. We propose that a better understanding of TRP channels and their modulators may facilitate the development of more selective and effective therapies to treat visceral hypersensitivity.

  8. Drug-eluting stent thrombosis: the Kounis hypersensitivity-associated acute coronary syndrome revisited.

    PubMed

    Chen, Jack P; Hou, Dongming; Pendyala, Lakshmana; Goudevenos, John A; Kounis, Nicholas G

    2009-07-01

    The advent of drug-eluting stents (DES) has revolutionized the field of interventional cardiology. Their dramatic and persistent restenotic and target lesion revascularization advantages are unquestioned. However, concerns over the rare but potentially catastrophic risk of stent thrombosis (ST) have tempered universal acceptance of these devices. Although the precise mechanism of DES ST is undoubtedly multifactorial and as yet not fully elucidated, delayed or incomplete endothelial healing clearly plays a pivotal role. Detailed histopathological data have implicated a contributory allergic or hypersensitivity component, as verified by the Food and Drug Administration's Manufacturer and User Device Experience Center and the Research on Adverse Drug/device events And Reports (RADAR) project. These findings thus suggest a potential connection with the Kounis syndrome, the concurrence of acute coronary events with allergic, hypersensitivity, anaphylactic, or anaphylactoid reactions. Potential culprits responsible for this phenomenon include: arachidonic acid metabolites such as leukotrienes and thromboxane, proteolytic enzymes such as chymase and tryptase, histamine, cytokines, and chemokines. Additionally, inflammatory cells such as macrophages, T-lymphocytes, and mast cells are probably also contributory. Autopsy-confirmed infiltrates of various inflammatory cells including lymphocytes, plasma cells, macrophages, and eosinophils have been reported in all 3 vascular wall layers and are reminiscent of those associated with the Kounis syndrome. Although the concurrence of acute coronary syndromes with hypersensitivity reactions has been long established, the specific association with DES ST remains unproven. Potential incorporation of hypersensitivity suppressive agents might represent a promising paradigm shift from efficacy to safety in future DES designs.

  9. The potential utility of iodinated contrast media (ICM) skin testing in patients with ICM hypersensitivity.

    PubMed

    Ahn, Young-Hwan; Koh, Young-Il; Kim, Joo-Hee; Ban, Ga-Young; Lee, Yeon-Kyung; Hong, Ga-Na; Jin, U-Ram; Choi, Byung-Joo; Shin, Yoo-Seob; Park, Hae-Sim; Ye, Young-Min

    2015-03-01

    Both immediate and delayed hypersensitivity reactions to iodinated contrast media (ICM) are relatively common. However, there are few data to determine the clinical utility of immunologic evaluation of ICM. To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity, 23 patients (17 immediate and 6 delayed reactions) were enrolled from 3 university hospitals in Korea. With 6 commonly used ICM including iopromide, iohexol, ioversol, iomeprol, iopamidol and iodixanol, skin prick (SPT), intradermal (IDT) and patch tests were performed. Of 10 patients with anaphylaxis, 3 (30.0%) and 6 (60.0%) were positive respectively on SPTs and IDTs with the culprit ICM. Three of 6 patients with urticaria showed positive IDTs. In total, 11 (64.7%) had positive on either SPT or IDT. Three of 6 patients with delayed rashes had positive response to patch test and/or delayed IDT. Among 5 patients (3 anaphylaxis, 1 urticaria and 1 delayed rash) taken subsequent radiological examinations, 3 patients administered safe alternatives according to the results of skin testing had no adverse reaction. However, anaphylaxis developed in the other 2 patients administered the culprit ICM again. With 64.7% (11/17) and 50% (3/6) of the sensitivities of corresponding allergic skin tests with culprit ICM for immediate and delayed hypersensitivity reactions, the present study suggests that skin tests is useful for the diagnosis of ICM hypersensitivity and for selecting safe ICM and preventing a recurrence of anaphylaxis caused by the same ICM.

  10. Glial pannexin1 contributes to tactile hypersensitivity in a mouse model of orofacial pain

    PubMed Central

    Hanstein, Regina; Hanani, Menachem; Scemes, Eliana; Spray, David C.

    2016-01-01

    Drug studies in animal models have implicated pannexin1 (Panx1) in various types of pain, including trigeminal hypersensitivity, neuropathic pain and migraine. However, the tested drugs have limited specificity and efficacy so that direct evidence for Panx1 contribution to pain has been lacking. We here show that tactile hypersensitivity is markedly attenuated by deletion of Panx1 in a mouse model of chronic orofacial pain; in this model, trigeminal ganglion Panx1 expression and function are markedly enhanced. Targeted deletion of Panx1 in GFAP-positive glia or in neurons revealed distinct effects. Panx1 deletion in GFAP-positive glia cells prevented hypersensitivity completely, whereas deletion of neuronal Panx1 reduced baseline sensitivity and the duration of hypersensitivity. In trigeminal ganglia with genetically encoded Ca2+ indicator in GFAP-positive glia or in neurons, both cell populations were found to be hyperactive and hyper-responsive to ATP. These novel findings reveal unique roles for GFAP-positive glial and neuronal Panx1 and describe new chronic pain targets for cell-type specific intervention in this often intractable disease. PMID:27910899

  11. Main ion channels and receptors associated with visceral hypersensitivity in irritable bowel syndrome

    PubMed Central

    de Carvalho Rocha, Heraldo Arcela; Dantas, Bruna Priscilla Vasconcelos; Rolim, Thaísa Leite; Costa, Bagnólia Araújo; de Medeiros, Arnaldo Correia

    2014-01-01

    Irritable bowel syndrome (IBS) is a very frequent functional gastrointestinal disorder characterized by recurrent abdominal