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Sample records for experimental hypersensitivity pneumonitis

  1. Blast cells transfer experimental hypersensitivity pneumonitis in guinea pigs

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  2. Chronic hypersensitivity pneumonitis.

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    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.

  3. Chronic hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Pereira CA

    2016-09-01

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

  4. Hypersensitivity pneumonitis: an immunopathology review.

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    Woda, Bruce A

    2008-02-01

    Hypersensitivity pneumonitis (HSP) is an immunologically mediated alveolar and interstitial lung disease caused by repeated inhalation of organic dusts and some occupational agents. The pathogenesis of HSP is uncertain. A number of unexplained features of HSP remain, namely (1) why do so few exposed individuals develop clinical HSP, (2) what triggers an acute episode after prolonged periods of previous sensitization, and (3) what leads to disease progression. This article considers these issues and aims to discuss and clarify current concepts in pathogenesis. Pertinent literature review in conjunction with the author's personal interpretive opinion. Current data suggest that individuals with a T(H)1 dominant response are likely to develop clinical disease. There is also some evidence that genetic factors such as polymorphisms in the major histocompatibility complex, tumor necrosis factor alpha, and tissue inhibitor of metalloproteinase 3 are associated with the development of or resistance to the disease.

  5. Hazards of the 'hard cash': hypersensitivity pneumonitis.

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    Kupeli, Elif; Karnak, Demet; Sak, Serpil Dizbay; Kayacan, Oya

    2010-01-01

    Hypersensitivity pneumonitis (HP) is a nonimmunoglobulin E-related immune-mediated parenchymal lung disease. A 45-year-old woman who was a lifelong nonsmoker with a six-month history of frequent episodes of cough and dyspnea was admitted to hospital. She had been working as a money counter for 20 years at a central bank. Bibasilar crackles on lung auscultation, ground-glass opacities and a mosaic pattern on high-resolution computed tomography, restrictive abnormality on pulmonary function tests and mild hypoxemia were the prominent findings. Bronchoalveolar lavage fluid analysis revealed a predominance of CD4-positive T cells, and she tested positive on her natural challenge test. She was diagnosed with subacute HP based on established criteria. She was advised to discontinue counting fresh banknotes. Prednisolone was commenced, then tapered to discontinue in the ensuing six months. Clinical and radiological improvement was achieved within two months. To the authors' knowledge, the present report is the first to describe 'hard cash HP', possibly caused by chipping dust or printing dye.

  6. Hypersensitivity pneumonitis: a complex lung disease.

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    Riario Sforza, Gian Galeazzo; Marinou, Androula

    2017-01-01

    Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a respiratory syndrome involving the lung parenchyma and specifically the alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic reaction. Such reaction is secondary to a repeated and prolonged inhalation of different types of organic dusts or other substances to which the patient is sensitized and hyper responsive, primarily consisting of organic dusts of animal or vegetable origin, more rarely from chemicals. The prevalence of HP is difficult to evaluate because of uncertainties in detection and misdiagnosis and lacking of widely accepted diagnostic criteria, and varies considerably depending on disease definition, diagnostic methods, exposure modalities, geographical conditions, agricultural and industrial practices, and host risk factors. HP can be caused by multiple agents that are present in work places and in the home, such as microbes, animal and plant proteins, organic and inorganic chemicals. The number of environment, settings and causative agents is increasing over time. From the clinical point of view HP can be divided in acute/subacute and chronic, depending on the intensity and frequency of exposure to causative antigens. The mainstay in managing HP is the avoidance of the causative antigen, though the complete removal is not always possible due to the difficulties to identify the agent or because its avoidance may lead to major changes in life style or occupational settings. HP is a complex syndrome that needs urgently for more stringent and selective diagnostic criteria and validation, including wider panels of IgG, and a closer collaboration with occupational physicians, as part of a multidisciplinary expertise.

  7. A haemodynamic study of pulmonary hypertension in chronic hypersensitivity pneumonitis.

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    Oliveira, Rudolf K F; Pereira, Carlos A C; Ramos, Roberta P; Ferreira, Eloara V M; Messina, Carolina M S; Kuranishi, Lilian T; Gimenez, Andrea; Campos, Orlando; Silva, Célia M C; Ota-Arakaki, Jaquelina S

    2014-08-01

    Chronic hypersensitivity pneumonitis is a common fibrotic interstitial lung disease. The prevalence of pulmonary hypertension diagnosed by right heart catheterisation and its cardiopulmonary function findings in patients with chronic hypersensitivity pneumonitis are unknown. Consecutive symptomatic patients with chronic hypersensitivity pneumonitis were prospectively evaluated. All patients were submitted to right heart catheterisation, pulmonary function testing, a 6-min walk test, echocardiography, blood gas determination and N-terminal pro-brain natriuretic peptide analyses. Nonhypoxaemic patients also underwent incremental cardiopulmonary exercise testing. 50 patients underwent right heart catheterisation; 25 (50%) of these had pulmonary hypertension and 22 (44%) had a pre-capillary haemodynamic pattern. The patients with pre-capillary pulmonary hypertension had lower forced vital capacity (mean ± sd 50 ± 17% versus 69 ± 22% predicted, p<0.01), carbon monoxide diffusing capacity (37 ± 12% versus 47 ± 14% predicted, p<0.01), arterial oxygen tension (median (interquartile range) 59.0 (47.8-69.3) versus 73.0 (62.2-78.5) mmHg, p<0.01) and saturation after the 6-min walk test (78 ± 8% versus 86 ± 7%, p<0.01). In pre-capillary pulmonary hypertension, oxygen uptake was also lower at the anaerobic threshold (41 ± 11% versus 50 ± 8% predicted, p=0.04) and at peak exercise (12.8 ± 1.6 versus 15.0 ± 2.5 mL · kg(-1) · min(-1), p=0.02). Pre-capillary pulmonary hypertension is common in symptomatic chronic hypersensitivity pneumonitis and is related to interstitial lung disease severity. Additionally, pulmonary hypertension is more prevalent in hypoxaemic patients with impaired lung function and exercise capacity. ©ERS 2014.

  8. CT findings associated with survival in chronic hypersensitivity pneumonitis

    International Nuclear Information System (INIS)

    Chung, Jonathan H.; Montner, Steven M.; Adegunsoye, Ayodeji; Vij, Rekha; Noth, Imre; Strek, Mary E.; Oldham, Justin M.; Husain, Aliya N.

    2017-01-01

    To identify CT findings in chronic hypersensitivity pneumonitis (cHP) associated with survival. Two thoracic radiologists assessed CT scans for specific imaging findings and patterns in 132 subjects with cHP. Survival analyses were performed. The majority of subjects had an inconsistent with usual interstitial pneumonitis pattern on CT (55.3%,73/132). Hypersensitivity pneumonitis (HP) diagnosis on CT was less common in those with fibrosis (66.1%, 74/112) than those without fibrosis (85%,17/20). Smoking was associated with a lower prevalence of HP on CT (p=0.04). CT features of pulmonary fibrosis, especially traction bronchiectasis (HR 8.34, 95% CI 1.98-35.21) and increased pulmonary artery (PA)/aorta ratio (HR 2.49, 95% CI 1.27-4.89) were associated with worse survival, while ground-glass opacity (HR 0.31, 95% CI 0.12-0.79) was associated with improved survival. Survival association with imaging was less pronounced after adjustment for gender, age and physiology score. A substantial proportion of cHP cases have a non-HP-like appearance. Ground-glass opacity, pulmonary fibrosis features and elevated PA/aorta ratio on CT likely reflect varying degrees of disease severity in cHP and may inform future clinical prediction models. (orig.)

  9. CT findings associated with survival in chronic hypersensitivity pneumonitis

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    Chung, Jonathan H.; Montner, Steven M. [University of Chicago Medical Center, Department of Radiology, Chicago, IL (United States); Adegunsoye, Ayodeji; Vij, Rekha; Noth, Imre; Strek, Mary E. [University of Chicago Medical Center, Section of Pulmonary/Critical Care, Department of Medicine, Chicago, IL (United States); Oldham, Justin M. [University of California at Davis, Section of Pulmonary/Critical Care, Department of Medicine, Sacramento, CA (United States); Husain, Aliya N. [University of Chicago Medical Center, Department of Pathology, Chicago, IL (United States)

    2017-12-15

    To identify CT findings in chronic hypersensitivity pneumonitis (cHP) associated with survival. Two thoracic radiologists assessed CT scans for specific imaging findings and patterns in 132 subjects with cHP. Survival analyses were performed. The majority of subjects had an inconsistent with usual interstitial pneumonitis pattern on CT (55.3%,73/132). Hypersensitivity pneumonitis (HP) diagnosis on CT was less common in those with fibrosis (66.1%, 74/112) than those without fibrosis (85%,17/20). Smoking was associated with a lower prevalence of HP on CT (p=0.04). CT features of pulmonary fibrosis, especially traction bronchiectasis (HR 8.34, 95% CI 1.98-35.21) and increased pulmonary artery (PA)/aorta ratio (HR 2.49, 95% CI 1.27-4.89) were associated with worse survival, while ground-glass opacity (HR 0.31, 95% CI 0.12-0.79) was associated with improved survival. Survival association with imaging was less pronounced after adjustment for gender, age and physiology score. A substantial proportion of cHP cases have a non-HP-like appearance. Ground-glass opacity, pulmonary fibrosis features and elevated PA/aorta ratio on CT likely reflect varying degrees of disease severity in cHP and may inform future clinical prediction models. (orig.)

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

    Science.gov (United States)

    Kreiss, K; Cox-Ganser, J

    1997-10-01

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

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

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    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.

  12. Hypersensitivity pneumonitis with Mycobacterium avium complex among spa workers.

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    Moraga-McHaley, Stephanie Ann; Landen, Michael; Krapfl, Heidi; Sewell, C Mack

    2013-01-01

    The New Mexico Department of Health (NMDOH) investigated the cause of two cases of hypersensitivity pneumonitis (HP) in spa maintenance workers with laboratory confirmed Mycobacterium avium complex (MAC). The investigation occurred in tandem with worker protection and swimming pool regulatory investigations by the New Mexico Environment Department at the spa where the workers were employed. The investigation was conducted in order to identify unreported cases, exposure source(s), and to prevent further worker exposure. NMDOH surveyed 57 spa employees about symptoms and exposures, categorized jobs according to self-reported exposure to water, and computed odds ratios for symptom reporting by exposure category. Environmental isolates from spa water and filter swabs were cultured and compared to patient isolates by the Environmental and Applied Microbiology Team, Centers for Disease Control and Prevention (CDC). Workers with the highest exposure reported more HP-like symptoms (OR = 9.6), as did intermediate exposure workers (OR = 6.5), compared to workers with no aerosolized water exposure. Two of 13 environmental isolates were closely related to one of the patient isolates. Workers were likely exposed during spray cleaning of cartridge filters in a poorly ventilated work space. Recommendations include inhibiting organism growth in spa systems, assuring the use of respiratory protection, and adequately ventilating work spaces where filters and equipment are cleaned.

  13. Hazards of the ‘Hard Cash’: Hypersensitivity Pneumonitis

    Directory of Open Access Journals (Sweden)

    Elif Kupeli

    2010-01-01

    Full Text Available Hypersensitivity pneumonitis (HP is a nonimmunoglobulin E-related immune-mediated parenchymal lung disease. A 45-year-old woman who was a lifelong nonsmoker with a six-month history of frequent episodes of cough and dyspnea was admitted to hospital. She had been working as a money counter for 20 years at a central bank. Bibasilar crackles on lung auscultation, ground-glass opacities and a mosaic pattern on high-resolution computed tomography, restrictive abnormality on pulmonary function tests and mild hypoxemia were the prominent findings. Bronchoalveolar lavage fluid analysis revealed a predominance of CD4-positive T cells, and she tested positive on her natural challenge test. She was diagnosed with subacute HP based on established criteria. She was advised to discontinue counting fresh banknotes. Prednisolone was commenced, then tapered to discontinue in the ensuing six months. Clinical and radiological improvement was achieved within two months. To the authors’ knowledge, the present report is the first to describe ‘hard cash HP’, possibly caused by chipping dust or printing dye.

  14. Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis

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    Ayodeji Adegunsoye

    2017-08-01

    Full Text Available In chronic hypersensitivity pneumonitis (CHP, lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival. Patients with CHP were identified. Demographic features, pulmonary function tests, incidence of treatment-emergent adverse events (TEAEs and transplant-free survival were characterised, compared and analysed between patients stratified by immunosuppressive therapy. A multicentre comparison was performed across four independent tertiary medical centres. Among 131 CHP patients at the University of Chicago medical centre (Chicago, IL, USA, 93 (71% received immunosuppressive therapy, and had worse baseline forced vital capacity (FVC and diffusing capacity, and increased mortality compared with those who did not. Compared to patients treated with prednisone alone, TEAEs were 54% less frequent with azathioprine therapy (p=0.04 and 66% less frequent with mycophenolate mofetil (p=0.002. FVC decline and survival were similar between treatment groups. Analyses of datasets from four external tertiary medical centres confirmed these findings. CHP patients who did not receive immunosuppressive therapy had better survival than those who did. Use of mycophenolate mofetil or azathioprine was associated with a decreased incidence of TEAEs, and no difference in lung function decline or survival when compared with prednisone alone. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP, but more studies are needed.

  15. Change in FVC and survival in chronic fibrotic hypersensitivity pneumonitis.

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    Gimenez, Andrea; Storrer, Karin; Kuranishi, Lilian; Soares, Maria Raquel; Ferreira, Rimarcs Gomes; Pereira, Carlos A C

    2018-04-01

    The predictive value of the decline in FVC by ≥10% on survival in patients with fibrotic hypersensitivity pneumonitis is unknown. Of 112 patients included, 66 (59%) had surgical lung biopsies. Patients with ≥10% decline in predicted FVC after 6-12 months had a significantly increased risk of all-cause mortality (median survival 53 months, 95% CI 37 to 69 vs 139 months, 95% CI 66 to 212 months, p=0.007). On multivariate analysis remained associated with increasing mortality: decline in FVC by ≥10% (HR 4.13, 95% CI 1.96 to 8.70, p=0.005), lower FVC% (HR 1.03, 95% CI 1.01 to 1.05, p=0.003) and with decreasing mortality improvement with antigen avoidance (HR 0.18, 95% CI 0.04 to 0.77, p=0.021). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

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

    2016-03-15

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

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

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

    2006-10-01

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

  18. PENINGKATAN CD8 DAN IFN-γ PADA HYPERSENSITIVITY PNEUMONITIS (HP AKIBAT PAJANAN DEBU PENGGILINGAN PADI

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    Isa Ma'rufi

    2017-10-01

    Full Text Available Abstrak     Masalah klinis kesehatan kerja pada pekerja penggilingan padi saat ini adalah penyakit saluran pernafasan. Penelitian ini bertujuan untuk menganalisis peningkatan CD8 dan IFN-γ pada Pneumonitis Hipersensitif (HP akibat pajanan debu penggilingan padi pada mencit  (Musmusculus BALB/C. Penelitian yang dilakukan adalah penelitian eksperimental laboratoris dengan hewan coba mencit (Musmusculus BALB/C,  rancangan penelitian yang digunakan adalah Randomized the post test only control group design. Mencit  (Musmusculus BALB/C dipajan dengan debu penggilingan padi selama empat jam/hari selama tiga puluh hari dengan konsentrasi 0.50 mg/m3, 0.75 mg/m3, 1.00 mg/m3. Variabel bebas adalah debu penggilingan padi, sedangkan variabel tergantung adalah   CD8 dan IFN-γ, serta gambaran histopatologis paru mencit, sedangkan variabel kendali adalah strain, berat badan, dan umur. Hasil penelitian menunjukkan bahwa terjadi peningkatan kadar CD8 antara kontrol dengan perlakuan, dan secara statistik  ada perbedaan yang bermakna. Kemudian terjadi peningkatan IFN-γ dan secara statistik ada perbedaan yang bermakna antara kontrol dan perlakuan pada mencit  (Musmusculus BALB/C. Hasil penelitian dapat digunakan sebagai dasar upaya pencegahan dan pemberian terapi penyakit HP lebih dini sehingga dapat meningkatkan kualitas paru.   Kata Kunci: CD8, IFN-γ,  debu penggilingan padi     Abtract   The purpose of this research was to analyze increase of CD8  and IFN-γ of Hypersensitivity Pneumonitis (HP as a result from the exposure of dust from paddy milling on mice (MusmusculusBALB/C. The research done was a laboratory experimental research with mice (MusMusculus as experimental animal.  The research design used was the post only control group design using mice (MusMusculus Balb/c as experimental animal.  Mice (Musmusculus Balb/c were exposed to dust from paddy milling for four (4 hours/day and it was done for thirty (30 days with the exposed

  19. A case of hypersensitivity pneumonitis with giant cells in a female dental technician.

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    Kim, Yong-Hyun; Chung, Yun Kyung; Kim, Changhwan; Nam, Eun Suk; Kim, Hyun-Jun; Joo, Youngsu

    2013-10-04

    Dental technicians are exposed to methyl methacrylate(MMA) and hard metal dusts while working, and several cases of hypersensitivity pneumonitis caused by the exposure have been reported. The authors experienced a case of hypersensitivity pneumonitis in a female dental technician who had 10 years' work experience and report the case with clinical evidence. The patient's work, personal, social, and past and present medical histories were investigated based on patient questioning and medical records. Furthermore, the workplace conditions and tools and materials the patient worked with were also evaluated. Next, the pathophysiology and risk factors of pneumonitis were studied, and studies on the relationship between hypersensitivity pneumonitis and a dental technician's exposure to dust were reviewed. Any changes in the clinical course of her disease were noted for evaluation of the work-relatedness of the disease. The patient complained of cough and sputum for 1 year. In addition, while walking up the stairs, the patient was not able to ascend without resting due to dyspnea. She visited our emergency department due to epistaxis, and secondary hypertension was incidentally suspected. Laboratory tests including serologic, electrolyte, and endocrinologic tests and a simple chest radiograph showed no specific findings, but chest computed tomography revealed a centrilobular ground-glass pattern in both lung fields. A transbronchial biopsy was performed, and bronchoalveolar washing fluid was obtained. Among the findings of the laboratory tests, microcalcification, noncaseating granuloma containing foreign body-type giant cells, and metal particles within macrophages were identified histologically. Based on these results, hypersensitivity pneumonitis was diagnosed. The patient stopped working due to admission, and she completely quit her job within 2 months of restarting work due to reappearance of the symptoms. In this study, the patient did not have typical radiologic

  20. Histographical presentation of frequency distribution of attenuation numbers of hypersensitivity pneumonitis

    International Nuclear Information System (INIS)

    Uchino, Akira; Nishitani, Hiromu; Onitsuka, Hideo; Baba, Hiromi; Kawahira, Kozaburo

    1981-01-01

    Based on the attenuation numbers in computed tomography of the chest, histograms for 5 patients with hypersensitivity pneumonitis were analysed. For analysis of histograms, we established 3 parameters: A, tan theta, and M. Of histograms in normal subjects, maximum inspiration scan was more stable than maximum expiration scan, and parameter A was most stable. In patients with hypersensitivity pneumonitis, histograms shifted to the range of higher attenuation numbers than normal subjects. Follow up studies showed decrease in the shift, but parameter A and M of maximum inspiration scan never reached to normal ranges. This suggested that organic parenchymal changes never disappeared completely, even in clinical remission stage. Therefore, parameter A or M of maximum inspiration scan was adequate for analysis, and histographic analysis of chest CT scan was considered to be useful also for early detections and follow-up studies of all diffuse pulmonary disorders. (author)

  1. Chronic hypersensitivity pneumonitis: high resolution computed tomography patterns and pulmonary function indices as prognostic determinants

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    Walsh, Simon L.F.; Devaraj, Anand; Hansell, David M. [Royal Brompton Hospital, Department of Radiology, London (United Kingdom); Sverzellati, Nicola [University of Parma, Department of Clinical Sciences, Section of Radiology, Parma (Italy); Wells, Athol U. [Royal Brompton Hospital, Interstitial Lung Diseases Unit, London (United Kingdom)

    2012-08-15

    To investigate high resolution computed tomography (HRCT) and pulmonary function indices (PFTs) for determining prognosis in patients with chronic fibrotic hypersensitivity pneumonitis (CHP). Case records, PFTs (FEV{sub 1}, FVC and DLco) and HRCTs of ninety-two patients with chronic hypersensitivity pneumonitis were evaluated. HRCT studies were scored by two observers for total disease extent, ground-glass opacification, fine and coarse reticulation, microcystic and macrocystic honeycombing, centrilobular emphysema and consolidation. Traction bronchiectasis within each pattern was graded. Using Cox proportional hazards regression models the prognostic strength of individual HRCT patterns and pulmonary function test variables were determined. There were forty two deaths during the study period. Increasing severity of traction bronchiectasis was the strongest predictor of mortality (HR 1.10, P < 0.001, 95%CI 1.04-1.16). Increasing global interstitial disease extent (HR 1.02, P = 0.02, 95%CI 1.00-1.03), microcystic honeycombing (HR 1.09, P = 0.019, 95%CI 1.01-1.17) and macrocystic honeycombing (HR 1.06, P < 0.01, 95%CI 1.01-1.10) were also independent predictors of mortality. In contrast, no individual PFT variable was predictive of mortality once HRCT patterns were accounted for. HRCT patterns, in particular, severity of traction bronchiectasis and extent of honeycombing are superior to pulmonary function tests for predicting mortality in patients with CHP. (orig.)

  2. Chronic hypersensitivity pneumonitis: high resolution computed tomography patterns and pulmonary function indices as prognostic determinants

    International Nuclear Information System (INIS)

    Walsh, Simon L.F.; Devaraj, Anand; Hansell, David M.; Sverzellati, Nicola; Wells, Athol U.

    2012-01-01

    To investigate high resolution computed tomography (HRCT) and pulmonary function indices (PFTs) for determining prognosis in patients with chronic fibrotic hypersensitivity pneumonitis (CHP). Case records, PFTs (FEV 1 , FVC and DLco) and HRCTs of ninety-two patients with chronic hypersensitivity pneumonitis were evaluated. HRCT studies were scored by two observers for total disease extent, ground-glass opacification, fine and coarse reticulation, microcystic and macrocystic honeycombing, centrilobular emphysema and consolidation. Traction bronchiectasis within each pattern was graded. Using Cox proportional hazards regression models the prognostic strength of individual HRCT patterns and pulmonary function test variables were determined. There were forty two deaths during the study period. Increasing severity of traction bronchiectasis was the strongest predictor of mortality (HR 1.10, P < 0.001, 95%CI 1.04-1.16). Increasing global interstitial disease extent (HR 1.02, P = 0.02, 95%CI 1.00-1.03), microcystic honeycombing (HR 1.09, P = 0.019, 95%CI 1.01-1.17) and macrocystic honeycombing (HR 1.06, P < 0.01, 95%CI 1.01-1.10) were also independent predictors of mortality. In contrast, no individual PFT variable was predictive of mortality once HRCT patterns were accounted for. HRCT patterns, in particular, severity of traction bronchiectasis and extent of honeycombing are superior to pulmonary function tests for predicting mortality in patients with CHP. (orig.)

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

    Directory of Open Access Journals (Sweden)

    J. L. Pérez-Arellano

    1995-01-01

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

  4. Hypersensitivity Pneumonitis

    Science.gov (United States)

    ... breed animals or birds, cheese washers, woodworkers, and wine makers—have a greater chance of exposure to ... this test, talk to your doctor about the benefits and possible risks of this procedure. Lung biopsies ...

  5. Occupational Hypersensitivity Pneumonitis Reported to the Czech National Registry of Occupational Diseases in the Period 1992-2005

    Czech Academy of Sciences Publication Activity Database

    Fenclová, Z.; Pelclová, D.; Urban, P.; Navrátil, Tomáš; Klusáčková, P.; Lebedová, J.

    2009-01-01

    Roč. 47, č. 4 (2009), s. 443-448 ISSN 0019-8366 Institutional research plan: CEZ:AV0Z40400503 Keywords : Hypersensitivity pneumonitis * Incidence * Branch of economic activity * Occupation Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.215, year: 2009

  6. Hypersensitivity pneumonitis. A series of nine cases with surgical lung biopsy

    Directory of Open Access Journals (Sweden)

    Ricardo A Gómez Tejada

    2017-12-01

    Full Text Available In a series of nine patients with histopathological diagnosis of hypersensitivity pneumonitis, we retrospectively evaluated clinical data, exposure related factors, pulmonary function tests and chest computed tomography scans. A restrictive abnormality with reduction of diffusion capacity for carbon monoxide was mainly found. Chest scans showed fibrotic patterns in most cases; ground glass attenuation areas with mosaic pattern and consolidation in the rest. Exposure to avian antigens, cereal grains and air conditioners contaminated with fungi yeasts and bacteria, were suspected from clinical data in two-thirds of the cases. Since there are no unique features that allow differentiation from other interstitial lung diseases, a high clinical suspicion is required and a careful search of environmental exposure to possible antigens is needed that, together with clinical, radiological and pathological data, may lead to diagnosis.

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    Masahiro Ishizuka

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

  9. An onion farmer with a case of hypersensitivity pneumonitis caused by Aspergillus niger.

    Science.gov (United States)

    Sakamoto, Tomohiro; Yamasaki, Akira; Funaki, Yoshihiro; Harada, Tomoya; Okazaki, Ryota; Hasegawa, Yasuyuki; Sueda, Yuriko; Fukushima, Takehito; Morita, Masahito; Yamamoto, Akihiro; Kodani, Masahiro; Shimizu, Eiji

    2018-01-01

    A 62-year old man was admitted to our hospital with a 2-week complaint of a dry cough, general fatigue, and dyspnea on effort. He has been an onion farmer for several years and developed these symptoms after cleaning up onion peels with air compressors. A chest roentgenogram and computed tomography showed a ground glass shadow in the bilateral upper lung field. Cellular analysis of the bronchoalveolar lavage fluid showed elevated total cell numbers and lymphocytes. Transbronchial lung biopsies revealed a non-caseating granuloma with both epithelioid cells and Langhans giant cells. After the admission, these symptoms and radiological findings gradually improved without any treatment. Then, a returning-home provocation test was positive only when he worked cleaning up onion peels with air compressors. A. niger was cultured from his workplace and black mold from the onion peels. The precipitation antibody and the antigen were both positive for Aspergillus . Therefore, we diagnosed this case as hypersensitivity pneumonitis caused by inhalation of A. niger . Although hypersensitivity pneumonia caused by A. niger is rare, physicians should aware the possibility of this condition in farmers because A niger is ubiquitously present in several vegetables and fruits.

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

    Science.gov (United States)

    Gupta, Amit; Rosenman, Kenneth D

    2006-06-01

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

  11. Hypersensitivity pneumonitis associated with mushroom worker's lung: an update on the clinical significance of the importation of exotic mushroom varieties.

    Science.gov (United States)

    Moore, John E; Convery, Rory P; Millar, B Cherie; Rao, Juluri R; Elborn, J Stuart

    2005-01-01

    Hypersensitivity pneumonitis remains an important industrial disease in mushroom workers. It has a significant morbidity, and early diagnosis and removal from exposure to the antigen are critically important in its management. Recently, several new allergens have been described, particularly those from mushroom species originating in the Far East, which are of clinical significance to workers occupationally exposed to such allergens in cultivation, picking, and packing of commercial mushroom crops. Importing of exotic mushrooms including Shiitake is common in EU countries, and some of the exotic species of mushrooms are cultivated for local markets. This practice may contribute to an increase in clinical cases of mushroom hypersensitivity pneumonitis. This update reviews the recent literature and examines changing trends of mushroom worker's lung, with increased movement of commercial product and labour markets worldwide.

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, Joseph; Mak, S.M.; Mok, W.; Hansell, D.M. [Royal Brompton and Harefield NHS Foundation Trust, Department of Radiology, Royal Brompton Hospital, London (United Kingdom); Bartholmai, B.J. [Mayo Clinic Rochester, Division of Radiology, Rochester, MN (United States); Rajagopalan, S.; Karwoski, R. [Mayo Clinic Rochester, Biomedical Imaging Resource, Rochester, MN (United States); Della Casa, G. [Universita degli Studi di Modena e Reggio Emilia, Modena, Emilia-Romagna (Italy); Sugino, K. [Toho University Omori Medical Centre, Tokyo (Japan); Walsh, S.L.F. [Kings College Hospital, London (United Kingdom); Wells, A.U. [Royal Brompton and Harefield NHS Foundation Trust, Interstitial Lung Disease Unit, Royal Brompton Hospital, London (United Kingdom)

    2017-09-15

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

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

    Directory of Open Access Journals (Sweden)

    Joana Cardoso

    2014-04-01

    Full Text Available Hypersensitivity pneumonitis (HP, or extrinsic allergic alveolitis, is an immunologically mediated disease resulting from the inhalation of organic substances that trigger an inflammatory response in the alveolar wall, bronchioles, and interstitium in susceptible individuals. Although HP is predominantly an occupational disease, seen in adulthood, cases in children have been described. The diagnosis of HP requires a high degree of suspicion. The treatment consists in avoiding contact with the antigen, and, in some cases, systemic corticosteroids might be necessary in order to prevent its progression to pulmonary fibrosis. We report the clinical cases of three children with a history of contact with birds and a family history of HP. All three patients presented with cough and dyspnea on exertion. The disease was diagnosed on the basis of the clinical history and ancillary diagnostic test results consistent with the diagnosis, including a predominance of lymphocytes (> 60%, CD8+ T lymphocytes in particular in bronchoalveolar lavage fluid and a ground-glass pattern seen on HRCT of the chest. Early diagnosis is crucial in order to prevent HP from progressing to pulmonary fibrosis. Hereditary factors seem to influence the onset of the disease.

  15. Immunoglobulin free light chains are increased in hypersensitivity pneumonitis and idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Tom Groot Kormelink

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

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

    International Nuclear Information System (INIS)

    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 FCγ-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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2010-02-01

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

  20. Neumonitis por hipersensibilidad en la ciudad de México Hypersensitivity pneumonitis in Mexico City

    Directory of Open Access Journals (Sweden)

    José G. Carrillo-Rodríguez

    2000-06-01

    Full Text Available OBJETIVO: Determinar la asociación entre la zona urbana de origen del paciente en la ciudad de México y la prevalencia de neumonitis por hipersensibilidad inducida por antígeno aviario. MATERIAL Y MÉTODOS: Se trata de un estudio de casos y controles realizado en el Instituto Nacional de Enfermedades Respiratorias, en la ciudad de México, en el año de 1999. Se estudiaron 109 casos con neumonitis por hipersensibilidad y 184 controles: de éstos, 39, con fibrosis pulmonar idiopática; 63, con tuberculosis pulmonar, y 82, con asma. La ciudad de México y las zonas conurbadas se dividieron en cinco zonas geográficas: centro, noreste, sureste, noroeste y el suroeste. Se calcularon las prevalencias de las diferentes enfermedades por zona urbana de los pacientes que participaron en el estudio; como medida de asociación, se estimó la razón de momios, con un intervalo de confianza al 95%. Asimismo, se realizó regresión logística múltiple ajustando por edad, sexo y estrato socioeconómico. RESULTADOS: Ochenta casos de neumonitis por hipersensibilidad se concentraron en el sur del noreste de las zonas conurbadas y la parte norte del sureste de la ciudad de México, 48 y 32, respectivamente (RM= 3.86, IC 95% 2.17-6.96. Treinta y seis controles de asma se localizaron en el suroeste de la ciudad de México, zona donde se ubica el Intituto Nacional de Enfermedades Respiratorias (pOBJECTIVE: To investigate the association between the urban area of origin of patients and the prevalence of hypersensitivity pneumonitis (HP, induced by avian antigens. MATERIAL AND METHODS: A case-control study was conducted in 1999 at the National Institute of Respiratory Diseases (NIRD. Cases were 109 consecutive HP patients and controls were 184 patients: 39 with idiopathic pulmonary fibrosis (IPF, 63 with pulmonary tuberculosis (PTB, and 82 with asthma. Mexico City and surrounding counties (SC were divided into 5 geographical areas: 1 Downtown; 2 North-East (NE; 3

  1. Hypersensitivity pneumonitis (extrinsic allergic alveolitis): high-resolution computed tomography findings; Pneumonite por hipersensibilidade (alveolite alergica extrinseca): achados na tomografia computadorizada de alta resolucao

    Energy Technology Data Exchange (ETDEWEB)

    Almeida Junior, Jose Guiomar de; Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Faculdade de Ciencias Medicas. Dept. de Radiologia]. E-mail: edmarchiori@zipmail.com.br; Escuissato, Dante L. [Parana Univ., Curitiba, PR (Brazil). Dept. de Radiologia; Souza Junior, Arthur Soares [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Dept. de Radiologia; Gasparetto, Emerson L. [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas; Nobre, Luiz Felipe [Santa Catarina Univ., Florianopolis, SC (Brazil); Irion, Klaus L. [Santa Casa de Misericordia de Porto Alegre, RS (Brazil). Pavilhao Pereira Filho. Servico de Radiologia

    2003-12-01

    Hypersensitivity pneumonitis, or extrinsic allergic alveolitis, is an immunologic disease of the lungs caused by inhaled chemicals or organics allergens. A lymphocytic inflammatory response in the peripheral airways and surrounding interstitial tissue occurs. In this study the high-resolution computed tomography findings of 13 patients with hypersensitivity pneumonitis were analyzed and discussed. The most frequent high-resolution computed tomography findings were: ground-glass opacities (92.3%), centrilobular nodules (38.4%) and air trapping (38.4%). Other findings included bronchiectasis (23.1%), consolidation (23.1%), crazy paving (7.7%), parenchymal bands (15.4%), linear opacities (7.7%), architectural distortion (7.7%), tracheal dilatation (7.7%), intralobular reticulate (7.7%), honeycombing (7.7%), emphysema (7.7%) and atelectasis (7.7%). In two of the 13 patients there was fibrosis (architectural distortion and honeycombing), which represents the chronic phase of the disease. (author)

  2. Epidemiology of occupational hypersensitivity pneumonitis; reports from the SWORD scheme in the UK from 1996 to 2015

    Science.gov (United States)

    Barber, C M; Wiggans, R E; Carder, M; Agius, R

    2017-01-01

    Objective To estimate the reported incidence of occupational hypersensitivity pneumonitis (OHP) in the UK and to consider whether the pattern of attributed causation has changed over time. Methods All cases of OHP reported to the SWORD scheme between January 1996 and December 2015 were classified into 1 of 10 categories of the suspected agent. Cases were grouped into four 5-year time periods to examine any changing pattern in incidence or suspected causation. For each time period, the annual incidence was calculated using the estimated number of reported cases and the working population of the UK. Results Between 1996 and 2015, there were 202 actual cases of OHP reported to SWORD, equating to an estimated 818 cases, when adjusting for the sampling ratio. Over this period, the annual UK incidence was 1.4 per million workers. The mean (SD) age of reported cases was 52 (13) years, and cases were four-times more likely to be men than women. Over the study period, there was a fall in the proportion of cases reported to be due to agricultural exposures (44–12%), and an increase in cases due to metalworking fluids (MWFs, 2–45%). Conclusions Over the last 20 years, the incidence of OHP in the UK has been ∼1–2 cases per million workers per year. Working with water-based MWFs is now the most commonly suspected causative exposure for OHP cases reported to the SWORD scheme in the UK. PMID:27919062

  3. Hypersensitivity pneumonitis to tobacco

    OpenAIRE

    MACEDO, SÍLVIA E.C.; ZAGO, ELICARLOS; TORRES, VÍTOR F.; BERGAMASCHI, FABIANO

    2001-01-01

    Pneumonite de hipersensibilidade (PH) é decorrente da inalação de antígenos orgânicos e/ou inorgânicos por indivíduos suscetíveis. Relata-se o caso de uma mulher de 18 anos, plantadora de tabaco em Pelotas, no Sul do Brasil, com dispnéia progressiva, tosse seca e emagrecimento havia 35 dias. Apresentava crepitações finas no tórax e a radiografia evidenciou infiltrado intersticial difuso. O diagnóstico de PH foi estabelecido pela história de exposição, achados tomográficos e exame anatomopatol...

  4. Fatal pneumonia by Legionella in a farmer with hypersensitivity pneumonitis Neumonía por Legionella con desenlace fatal en un granjero con neumonitis por hipersensibilidad

    Directory of Open Access Journals (Sweden)

    Vega García López

    2009-12-01

    Full Text Available Background: The retrospective investigation of a fatal sporadic Legionnaires' disease identified an unknown case of occupational hypersensitivity pneumonitis in a swine breeder. Methods: Chest high-resolution computed tomography, bronchoalveolar lavage, lung biopsy, arterial gasometry, pulmonary function tests and autopsy were performed. It was studied the presence of Legionella by serology and risk water samples were analyzed to identify the Legionella's source. Results: HP and Legionella pneumophila pneumonia diagnostics were confirmed. Lung fibrosis, a restrictive functional pattern, decreased diffusion, hypoxemia and bronchoalveolar lavage lymphocytosis were evidenced. Legionella´s source was detected in a shower and a positive serology in the patient. Autopsy verified pulmonary fibrosis and the septic shock leaded to Legionella causing the death. Conclusions: Chronic cough and pulmonary infiltrates in a farmer should suspect the presence of hypersensitivity pneumonitis. Later diagnosis carries a worse prognosis, the offending antigens exposure can't be avoided and fibrotic stage enhanced opportunity infection disease.Introducción: La investigación retrospectiva sobre un fallecimiento aislado por Legionelosis, hizo aflorar un caso de neumonitis por hipersensibilidad en un granjero cuidador de cerdos. Métodos: Se realizaron las siguientes pruebas: tomografía axial computerizada de alta resolución, lavado broncoalveolar, biopsia pulmonar, gasometría arterial, pruebas de función respiratoria y autopsia. Se estudió la presencia de Legionella por serología y se analizaron las muestras de fuentes de riesgo para identificar el foco de Legionella. Resultados: El estudio confirmó los diagnósticos de neumonitis por hipersensibilidad y neumonía por Legionella pneumophila. Las pruebas realizadas objetivaron la fibrosis pulmonar, un patrón respiratorio funcional restrictivo, un descenso de la difusión pulmonar, hipoxemia y la presencia de

  5. Evaluation of visual and computer-based CT analysis for the identification of functional patterns of obstruction and restriction in hypersensitivity pneumonitis.

    Science.gov (United States)

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

    2017-11-01

    To determine whether computer-based quantification (CALIPER software) is superior to visual computed tomography (CT) scoring in the identification of CT patterns indicative of restrictive and obstructive functional indices in hypersensitivity pneumonitis (HP). A total of 135 consecutive HP patients had CT parenchymal patterns evaluated quantitatively by both visual scoring and CALIPER. Results were evaluated against: forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DL CO ) and a composite physiological index (CPI) to identify which CT scoring method better correlated with functional indices. CALIPER-derived scores of total interstitial lung disease extent correlated more strongly than visual scores: FVC (CALIPER R = 0.73, visual R = 0.51); DL CO (CALIPER R = 0.61, visual R = 0.48); and CPI (CALIPER R = 0·70, visual R = 0·55). The CT variable that correlated most strongly with restrictive functional indices was CALIPER pulmonary vessel volume (PVV): FVC R = 0.75, DL CO R = 0.68 and CPI R = 0.76. Ground-glass opacity quantified by CALIPER alone demonstrated strong associations with restrictive functional indices: CALIPER FVC R = 0.65; DL CO R = 0.59; CPI R = 0.64; and visual = not significant. Decreased attenuation lung quantified by CALIPER was a better morphological measure of obstructive lung disease than equivalent visual scores as judged by relationships with TLC (CALIPER R = 0.63 and visual R = 0.12). All results were maintained on multivariate analysis. CALIPER improved on visual scoring in HP as judged by restrictive and obstructive functional correlations. Decreased attenuation regions of the lung quantified by CALIPER demonstrated better linkages to obstructive lung physiology than visually quantified CT scores. A novel CALIPER variable, the PVV, demonstrated the strongest linkages with restrictive functional indices and could represent a new

  6. Copper hypersensitivity

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-09-01

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

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

    International Nuclear Information System (INIS)

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

    1991-01-01

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

  9. Decreased delayed hypersensitivity to tuberculin demonstrated in experimental leptospirosis in guinea pigs

    DEFF Research Database (Denmark)

    Colding, H; Johansen, K S; Bentzon, M W

    1976-01-01

    Skin reactivity to tuberculin has been studied during the course of experimental leptospirosis in guinea pigs. A depression of the delayed hypersensitivity to tuberculin was demonstrated in the infected animals. The depression was most pronounced when icterus had developed. The depression...

  10. [A case of flomoxef-induced pneumonitis].

    Science.gov (United States)

    Wako, Y; Hamauzu, T; Tamura, M; Yokote, M; Yokote, M; Shoji, S; Takikawa, H; Miyake, K; Yamanaka, M; Goto, H

    1992-04-01

    We report a case of flomoxef-induced pneumonitis. A 22-year-old man was treated with flomoxef following liver biopsy. A few days later he developed a high fever and severe dyspnea, and his chest X-ray film revealed diffuse reticulo-nodular shadows in both lung fields. We suspected interstitial pneumonitis due to flomoxef, and pulse therapy with methylprednisolone was started. He showed rapid recovery of symptoms and marked regression of pulmonary infiltration in his chest X-ray. Lymphocyte stimulation test was positive to flomoxef, which was compatible with the diagnosis of drug-induced pneumonitis. To our knowledge, there has been no previous case of pulmonary hypersensitivity to flomoxef reported in Japan.

  11. Risk of radiation-induced pneumonitis after helical and static-port tomotherapy in lung cancer patients and experimental rats

    International Nuclear Information System (INIS)

    Zhang, Xianglan; Shin, You Keun; Zheng, Zhenlong; Zhu, Lianhua; Lee, Ik Jae

    2015-01-01

    Radiotherapy (RT) is one of the major non-operative treatment modalities for treating lung cancer. Tomotherapy is an advanced type of intensity-modulated radiotherapy (IMRT) in which radiation may be delivered in a helical fashion. However, unexpected pneumonitis may occur in patients treated with tomotherapy, especially in combination with chemotherapy, as a result of extensive low-dose radiation of large lung volumes. The aim of our study was to investigate the risk of radiation-induced pneumonitis after helical-mode and static-mode tomotherapy in patients with lung cancer and in an animal model. A total of 63 patients with primary lung cancer who were treated with static or helical tomotherapy with or without concurrent chemoradiotherapy (CCRT) were analyzed. Additionally, rats with radiation-induced pulmonary toxicity, which was induced by the application of helical or static tomography with or without CCRT, were evaluated. Helical-mode tomotherapy resulted in a significantly higher rate of late radiation pneumonitis in lung cancer patients than static-mode tomotherapy when evaluated by the Radiation Therapy Oncology Group (RTOG) and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) scoring system. In the animal model, helical tomotherapy alone induced significantly higher expression of interleukin (IL)-1α, IL-1β, IL-6, and transforming growth factor (TGF)-β in lung specimens, especially on the untreated side, compared to static tomotherapy alone. Additionally, rats treated with helical tomotherapy and CCRT demonstrated significantly higher expression of inflammatory cytokines compared to those treated with static tomotherapy and CCRT. Rat models treated with tomotherapy with or without CCRT could present similar patterns of pulmonary toxicity to those shown in lung cancer patients. The models can be used in further investigations of radiation induced pulmonary toxicity

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  13. Peracute radiation pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Dvorak, E

    1982-01-01

    Progressive tendencies in curative radiation therapy approach in the treatment of bronchogenic carcinoma will generally prolong a treatment course and modify the manifestation of radiation pneumonitis. There will probably be a tendency for an earlier onset of its acute phase, especially if the irradiated lung was atelectatic with or without post-obstructive pneumonia or if there were changes of chronic pulmonary disease. A peracute of radiation pneumonitis after a tumor dose of 6400 cGy in 29 fractions over 48 days starting within one week after the completion of irradiation is documented and discussed. Literature dealing with clinical, pathological, pathophysiological, and radiographic manifestations of radiation pneumonitis is shortly reviewed. Usage of corticosteroid therapy in the acute phase of radiation pneumonitis is described and controversial reports on this subject are mentioned. Beneficial effect of dexamethasone in the presented case is demonstrated on sequential radiograms.

  14. Voluntary wheel running delays disease onset and reduces pain hypersensitivity in early experimental autoimmune encephalomyelitis (EAE).

    Science.gov (United States)

    Benson, Curtis; Paylor, John W; Tenorio, Gustavo; Winship, Ian; Baker, Glen; Kerr, Bradley J

    2015-09-01

    Multiple sclerosis (MS) is classically defined by motor deficits, but it is also associated with the secondary symptoms of pain, depression, and anxiety. Up to this point modifying these secondary symptoms has been difficult. There is evidence that both MS and the animal model experimental autoimmune encephalomyelitis (EAE), commonly used to study the pathophysiology of the disease, can be modulated by exercise. To examine whether limited voluntary wheel running could modulate EAE disease progression and the co-morbid symptoms of pain, mice with EAE were allowed access to running wheels for 1h every day. Allowing only 1h every day of voluntary running led to a significant delay in the onset of clinical signs of the disease. The development of mechanical allodynia was assessed using Von Frey hairs and indicated that wheel running had a modest positive effect on the pain hypersensitivity associated with EAE. These behavioral changes were associated with reduced numbers of cFOS and phosphorylated NR1 positive cells in the dorsal horn of the spinal cord compared to no-run EAE controls. In addition, within the dorsal horn, voluntary wheel running reduced the number of infiltrating CD3(+) T-cells and reduced the overall levels of Iba1 immunoreactivity. Using high performance liquid chromatography (HPLC), we observed that wheel-running lead to significant changes in the spinal cord levels of the antioxidant glutathione. Oxidative stress has separately been shown to contribute to EAE disease progression and neuropathic pain. Together these results indicate that in mice with EAE, voluntary motor activity can delay the onset of clinical signs and reduce pain symptoms associated with the disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Bleomycin-induced pneumonitis

    NARCIS (Netherlands)

    S. Sleijfer (Stefan)

    2001-01-01

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

  16. Hypersensitivity vasculitis

    Science.gov (United States)

    Cutaneous small vessel vasculitis; Allergic vasculitis; Leukocytoclastic vasculitis ... Hypersensitivity vasculitis, or cutaneous small vessel vasculitis, is caused by: An allergic reaction to a drug or other foreign ...

  17. Radiation pneumonitis and fibrosis

    International Nuclear Information System (INIS)

    Shopova, V.; Salovsky, P.; Dancheva, V.

    2001-01-01

    The likelihood of toxic pulmonary lesions development as the result of radiation therapy for pulmonary carcinoma and breast cancer is discussed. Two possible forms of radiation induced changes are described, namely: classical radiation pneumonitis (RP) terminating with lung fibrosis circumscribed in the radiation zone, and sporadic RP giving rise to bilateral lymphatic alveolitis and manifestations outside the irradiation field. Attention is called to the fact that chemotherapy augments the risk of toxic lung damage occurrence. A number of markers for early RP diagnosis, including lactate dehydrogenase activity, KL-6, procollagen III, transforming growth factor β, C-reactive protein and partial oxygen pressure are listed. Therapeutic possibilities in coping with RP and pulmonary fibrosis are assayed. Apart from the standard therapeutic approach using corticosteroids and azatioprin, ideas are set forth concerning the application of some antioxidants, angiotensin converting enzyme inhibitors and γ-interferon. It is pointed out that radiation pneumonitis and pulmonary fibrosis treatment has an essential practical bearing on life expectancy and quality of life in a great number of cancer patients. (author)

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

    DEFF Research Database (Denmark)

    Møller, Janne; Hyldgaard, Charlotte; Kronborg-White, Sissel Brix

    2017-01-01

    antigen is important for the prognosis. We report two cases of HP caused by molds and atypical mycobacteria isolated from wind instruments. We present the first case of HP caused by bassoon playing and another case of HP caused by molds in a trombone. HP caused by fungi and bacteria in wind instruments...... may be much more common than previously thought. HP caused by fungi and bacteria in wind instruments is probably underdiagnosed; this calls for more clinical attention when HP is suspected....

  19. Hypersensitive tourists

    DEFF Research Database (Denmark)

    Jensen, Martin Trandberg

    2016-01-01

    This research note sets forth a new agendum for sensuous tourism scholarship. It departs in the neglected study of the embodied life of hypersensitive tourists, and argues that the ambiguousness of the sensuous be better understood. To contextualise this argument the following suggests that aller......This research note sets forth a new agendum for sensuous tourism scholarship. It departs in the neglected study of the embodied life of hypersensitive tourists, and argues that the ambiguousness of the sensuous be better understood. To contextualise this argument the following suggests...... that allergic tourists make up a contemporary and increasingly relevant empirical field through which to illuminate the dark sides of the sensuous. Finally, the note develops four analytical dimensions that structure critical sensuous scholarship....

  20. Metronidazole hypersensitivity.

    Science.gov (United States)

    Knowles, S; Choudhury, T; Shear, N H

    1994-03-01

    To report a case of a possible hypersensitivity reaction induced by metronidazole. An Asian woman with a history of recurrent vaginitis had previously developed localized erythema while on intravaginal metronidazole and nystatin. While receiving oral metronidazole for treatment of a current bacterial vaginosis, she developed chills, fever, generalized erythema, and a rash within 60 minutes of the first dose. Treatment with diphenhydramine was instituted. The following day while in the hospital, the patient's condition worsened; she experienced shortness of breath and increased edema of the extremities. Methylprednisolone was administered with diphenhydramine and her condition improved over the next 5 days. The patient's vaginitis was treated with gentian violet and she was discharged on a tapering dosage of prednisone. Metronidazole-induced cutaneous reactions and systemic hypersensitivity reactions are reviewed. Alternatives to metronidazole and other potential cross-reactive drugs are suggested for the treatment of recurrent vaginitis. Although the patient's initial reaction to metronidazole represented a rare event, written documentation and communication in the patient's native language may have prevented the subsequent severe hypersensitivity reaction.

  1. Radiation pneumonitis in breast cancer

    International Nuclear Information System (INIS)

    Ferrino, R.; Carvalho, H.A.; Gomes, H.C.; Kuang, L.F.; Aguilar, P.B.; Lederman, M.V.

    1987-01-01

    Forty-nine observations of patients with breast cancer frm 1980 to 1985 were reviewed. All of them received radiotherapy. In 44.9% radiologic findings of radiation pneumonitis were detected and only 9% presented mild or moderate respiratory symptoms. (M.A.C.) [pt

  2. Pneumonitis following infradiaphragmatic irradiation in Hodgkin's disease

    International Nuclear Information System (INIS)

    Zierhut, D.; Flentje, M.; Kalle, A. von; Moeller, P.

    1992-01-01

    A case is reported on radiation pneumonitis in the left costodiaphragmatic sinus 6 weeks following combined chemo- and radiotherapy of Hodgkin's disease. Thoracotomy was performed in order to exclude a pulmonal relapse of Hodgkin's disease. Thereby the diagnosis of radiation pneumonitis was histologically proven. The development of pneumonitis after irradiation of the spleen may occur and has to be considered in the differential diagnosis of pulmonal affections. (orig.) [de

  3. The interstitial pneumonitis induced by cytostatics

    International Nuclear Information System (INIS)

    Dubrava, M.; Markova, I.; Mistina, L.

    1998-01-01

    The author presents a cause of 9-year old boy with ALL-F2B in the stage of the prevention treatment where in the its course the induced interstitial pneumonitis by cytostatics was developed. The bacterial, virus, mycological and parasitic causes of the interstitial pneumonitis on the basis of the bronchoscopy, BAL, CT, scintigraphy, laboratory and by cultivation were excluded. (authors)

  4. Chlorambucil-Induced Acute Interstitial Pneumonitis

    Directory of Open Access Journals (Sweden)

    Hammad Shafqat

    2014-01-01

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

  5. Effects of ongoing smoking on the development of radiation-induced pneumonitis in breast cancer and oesophagus cancer patients

    International Nuclear Information System (INIS)

    Johansson, S.; Franzen, L.; Henriksson, R.; Bjermer, L.

    1998-01-01

    Purpose: To investigate the influence of smoking on the development of radiation-induced pneumonitis in patients treated for breast and oesophagus cancer. Materials and methods: This is a retrospective study on 405 females diagnosed with primary unilateral breast cancer stages 1 and 2 and 201 oesophagus carcinoma patients. The possibilities in Sweden to obtain detailed information from different medical records were used to collect data on smoking habits, radiation treatment and spontaneously reported pneumonitis. Radiation-induced pneumonitis was defined as a combination of roentgenographic infiltrate in the lung field involving an irradiated area on the chest X-ray and clinical symptoms such as non-productive cough and dyspnoea. Results: Six breast cancer patients had spontaneously reported pneumonitis. Five of them were non-smokers (P=0.182) and the other was a former smoker. Eight of the oesophagus cancer patients had spontaneously reported radiation-induced clinical pneumonitis and they were all non-smokers (P=0.022), except one, who was a pipe smoker. None of the patients who were cigarette smokers were recorded as developing clinical pneumonitis after irradiation. Conclusion: These data could support the previous clinical observations and experimental studies that smoking depresses the frequency of radiation-induced pneumonitis. The present study as well as earlier observations could justify further studies concerning the possibility of an interaction of smoking with cancer treatment, both from the view of therapeutic failures and reduced adverse effects. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  6. Genetic evidence for an essential role of neuronally expressed IL-6 signal transducer gp130 in the induction and maintenance of experimentally induced mechanical hypersensitivity in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Constantin Cristina E

    2011-09-01

    Full Text Available Abstract Tenderness and mechanical allodynia are key symptoms of malignant tumor, inflammation and neuropathy. The proinflammatory cytokine interleukin-6 (IL-6 is causally involved in all three pathologies. IL-6 not only regulates innate immunity and inflammation but also causes nociceptor sensitization and hyperalgesia. In general and in most cell types including immune cells and sensory neurons, IL-6 binds soluble μ receptor subunits which heteromerizes with membrane bound IL-6 signal transducer gp130. In the present study, we used a conditional knock-out strategy to investigate the importance of signal transducer gp130 expressed in C nociceptors for the generation and maintenance of mechanical hypersensitivity. Nociceptors were sensitized to mechanical stimuli by experimental tumor and this nociceptor sensitization was preserved at later stages of the pathology in control mice. However, in mice with a conditional deletion of gp130 in Nav1.8 expressing nociceptors mechanical hypersensitivity by experimental tumor, nerve injury or inflammation recovery was not preserved in the maintenance phase and nociceptors exhibited normal mechanical thresholds comparable to untreated mice. Together, the results argue for IL-6 signal transducer gp130 as an essential prerequisite in nociceptors for long-term mechanical hypersensitivity associated with cancer, inflammation and nerve injury.

  7. CT appearance of amiodarone-induced pneumonitis

    International Nuclear Information System (INIS)

    Nicholson, A.A.; Hayward, C.

    1989-01-01

    Basal peripheral pleuroparenchymal opacities are described on CT of early cryptogenic fibrosing alveolitis, asbestosis and bleomycin pneumonitis. These diseases may be caused by free radical effects on phospholipid metabolism causing cell wall damage. Amiodarone hydrochloride alters phospholipid synthesis metabolically. Amiodarone pneumonitis might be expected to show similar CT appearances. Sixteen patients who have developed new respiratory symptoms while taking amiodarone have been scanned prone and supine and at inspiration and expiration by means of a scanner with 2-mm sections at 1-cm intervals. All have been previously healthy nonsmokers with no relevant occupational history. Previous chest radiographs have been normal. Results are presented

  8. Chlamydial Pneumonitis: A Creepy Neonatal Disease

    Directory of Open Access Journals (Sweden)

    Kam Lun Hon

    2013-01-01

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

  9. Pneumonic Plague Transmission, Moramanga, Madagascar, 2015.

    Science.gov (United States)

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

    2017-03-01

    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.

  10. Legionnaire's disease - a puzzling pneumonic illness

    International Nuclear Information System (INIS)

    Stark, P.; Harvard Medical School, Boston, MA

    1981-01-01

    Three cases of a pneumonic illness are described, produced by a newly discovered causal organism. This is the weakly gram negative bacterium Legionelle pneumophila. The organisms is found intracellularly and can be recognised by direct or indirect immunofluorescence or the Dieterle staining. The clinical picture is characterised by a fulminating pneumonia with accompanying diarrhoea. Treatment of choice is intravenous erythromycin. (orig.) [de

  11. Clinical spectrum of cryptogenic organising pneumonitis.

    Science.gov (United States)

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

    1991-01-01

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

  12. Clinical and morphological aspects of radiation pneumonitis

    International Nuclear Information System (INIS)

    Schuh, D.; Eberhardt, H.J.

    1983-01-01

    Individually different radiation tolerance with relative dose dependence of the radioreaction could be revealed. Various radiation independent diseases of the lungs are predisposing factors of radiogenic pneumonitis. Even severe diffuse pneumonias can be clinically and radiologically asymptomatic. An enhanced toxic effect of combined cytostatic and radiotherapy could be demonstrated once more. Obviously irradiation causes lasting damage of the pulmonary tissue, being a changed but stereotype reaction to different irritations

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

    Science.gov (United States)

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

    2004-01-01

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

  14. Pneumonitis following infradiaphragmatic irradiation in Hodgkin's disease. Pneumonitis nach infradiaphragmaler Bestrahlung bei Morbus Hodgkin

    Energy Technology Data Exchange (ETDEWEB)

    Zierhut, D.; Flentje, M. (Radiologische Klinik, Heidelberg Univ. (Germany)); Kalle, A. von (Medizinische Poliklinik, Heidelberg Univ. (Germany)); Moeller, P. (Pathologisches Inst., Heidelberg Univ. (Germany))

    1992-12-01

    A case is reported on radiation pneumonitis in the left costodiaphragmatic sinus 6 weeks following combined chemo- and radiotherapy of Hodgkin's disease. Thoracotomy was performed in order to exclude a pulmonal relapse of Hodgkin's disease. Thereby the diagnosis of radiation pneumonitis was histologically proven. The development of pneumonitis after irradiation of the spleen may occur and has to be considered in the differential diagnosis of pulmonal affections. (orig.).

  15. Gallium-67 citrate imaging for the assessment of radiation pneumonitis

    International Nuclear Information System (INIS)

    Kataoka, Masaaki

    1989-01-01

    In order to evaluate its usefulness in the assessment of radiation pneumotinis, gallium-67 citrate ( 67 Ga) imaging was performed before and after radiation therapy (RT) on 103 patients with lung cancer. In 23 patients with radiation pneumonitis detected radiographically, abnormal 67 Ga uptake in sites other than tumors was found in all post-RT 67 Ga lung images. Three patterns of uptake were found: (A) focal uptake corresponding to the RT field (n=10); (B) diffuse uptake including the RT field (n=4); and (C) diffuse uptake outside the RT field (n=9). The area of 67 Ga uptake was consistent with that of interstitial pneumonitis as revealed histopathologically in 7 cases. 67 Ga uptake in pattern (C) was an indicator of poor prognosis for the patients with radiation pneumonitis. 67 Ga uptake in the patients with reversible pneumonitis disappeared with steroid therapy. Sixteen (20%) of 80 asymptomatic patients, in whose chest radiographs there was no finding of radiation pneumonitis, showed transient 67 Ga uptake. These were considered to occur in the subclinical radiation pneumonitis. These data suggest that 67 Ga imaging is more sensitive than chest radiography in the detection of radiation pneumonitis and is useful in the assessment of the extent and clinical course of radiation pneumonitis. (author)

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

    Science.gov (United States)

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

    2016-03-01

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

  17. Pulmonary function and fitness years after treatment for hypersensitivity pneumonitis during childhood

    DEFF Research Database (Denmark)

    Sisman, Yagmur; Buchvald, Frederik Fouirnaies; Blyme, Anne Katrine

    2016-01-01

    (fitness) are lacking. Hence, the aim of this study was to conduct a comprehensive study to determine the stability of pulmonary function and fitness in patients previously diagnosed with HP. METHODS: We performed a cross-sectional follow-up study with inclusion of longitudinal data if available...

  18. Drug hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Rashmi Kumari

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-06-01

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

  20. Food hypersensitivity by inhalation

    Directory of Open Access Journals (Sweden)

    Bahna Sami L

    2009-02-01

    Full Text Available Abstract 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.

  1. Metal Hypersensitivity in Orthodontic Patients

    Directory of Open Access Journals (Sweden)

    Sandhya Maheshwari Sanjeev K

    2015-06-01

    Full Text Available Orthodontic treatment of individuals with metal hypersensitivity is a matter of concern for the orthodontist. Orthodontic appliances contain metals like Nickel, Cobalt and Chromium etc. Metals may cause allergic reactions and are known as allergens. Reaction to these metals is due to biodegradation of metals in the oral cavity. This may lead to the formation of corrosion products and their exposure to the patient. Nickel is the most common metal to cause hypersensitivity reaction. Chromium ranks second among the metals, known to trigger allergic reactions. The adverse biological reactions to these metals may include hypersensitivity, dermatitis and asthma. In addition, a significant carcinogenic and mutagenic potential has been demonstrated. The orthodontist must be familiar with the best possible alternative treatment modalities to provide the safest, most effective care possible in these cases. The present article focuses on the issue of metal hypersensitivity and its management in orthodontic

  2. Lung function evaluation in acute postradiation pneumonitis

    International Nuclear Information System (INIS)

    Jassem, E.; Zandwijk, N. van; Jassem, J.; Badzio, A.

    1997-01-01

    The aim of this study was pulmonary function evaluation in patients with radiation pneumonitis (rp). Study group included 18 patients with symptomatic rp (8 with breast cancer, 6 with Hodgkin's disease and 4 with lung cancer) treated at the Netherland s Cancer inst. In Amsterdam between 1988 and 1994. The lung function tests were performed at the time of rp presentation and monthly thereafter and consisted of a standard spirometry: forced expiratory volume in 1 sec. (FEV1), vital capacity (VC) and diffusing capacity for carbon monoxide (DLCO) performed with the use of a single breath technique. The mean values of DLCO, VC, FEV1 and TLC at the time of rp presentation were 72.2%, 91.0% and 85.8% of predicted value (pv), respectively. The results of the a bone tests at the last examination (66.4%, 85.6%, 77.2% and 76.2% of pv), respectively, were lower than those registered at the time of rp presentation. The highest degree of functional deterioration included diffusion capacity; the mean of the lowest values of DLCO was 56.4% of pv. Usually the lowest value of DLCO accompanied the exacerbation of clinical symptoms. The results of this study demonstrated pulmonary function deterioration in patients with rp. (author)

  3. IL-6 is a potential marker for radiation pneumonitis: a prospective clinical study of circulating cytokines in predicting radiation pulmonary injury

    International Nuclear Information System (INIS)

    Chen Yuhchyau; Rubin, Philip; McDonald, Sandra; Finkelstein, Jacob; Smudzin, Therese; Hernady, Eric; Williams, Jacqueline

    1997-01-01

    -β (TGF-β), and procollagen III were measured before, weekly during, and periodically post-irradiation up to 6 months. Results: Six patients developed radiation pneumonitis 2 to 4 months after irradiation: two had symptoms treated without steroids (grade 1); three required steroids to relieve symptoms (grade 2); and one had fatal pneumonitis (grade 3). Radiographic mild fibrotic changes started as early as 1 month or as late as 4 months post-irradiation. Most fibrotic changes were progressive with longer radiographic follow-up. Three patients showed no fibrosis at all by 6 months; two had mild fibrotic changes; four had moderate fibrotic changes and eight developed severe fibrosis. Although not all the severe fibrosis was preceded by radiation pneumonitis, more patients with symptomatic pneumonitis developed radiographic severe fibrosis than those without clinical symptoms (p = 0.04). Pretreatment cytokine levels of IL-6, TNF, TGF-β, and procollagen III levels varied markedly among these individuals. Despite the significant variation of baseline cytokine profiles, percent IL-6 increase during the last two weeks of irradiation and the period immediately after irradiation was associated with and preceded symptomatic radiation pneumonitis. This change in IL-6 was significant (p < 0.05 at weeks 4 and 6) when compared to the group of patients without pneumonitis. Conclusions: In this prospective clinical study, percent increase of IL-6 during the last two weeks of thoracic radiotherapy and the period immediately after irradiation correlated with subsequent development of symptomatic pneumonitis. This is consistent with our laboratory finding in experimental animals. Thus changes in IL-6 levels during and immediately following irradiation may potentially serve as a predictor for radiation pneumonitis. All patients with radiation pneumonitis developed radiographic severe fibrosis on follow-up. A significant portion of patients without symptomatic pneumonitis also developed

  4. Women with dysmenorrhoea are hypersensitive to experimentally induced forearm ischaemia during painful menstruation and during the pain-free follicular phase.

    Science.gov (United States)

    Iacovides, S; Avidon, I; Baker, F C

    2015-07-01

    Monthly primary dysmenorrhoeic pain is associated with increased sensitivity to painful stimuli, particularly in deep tissue. We investigated whether women with dysmenorrhoea, compared with controls, have increased sensitivity to experimentally induced deep-tissue muscle ischaemia in a body area distant from that of referred menstrual pain. The sub-maximal effort tourniquet test was used to induce forearm ischaemia in 11 women with severe dysmenorrhoea and in nine control women both during menstruation and in the follicular phase of the menstrual cycle. Von Frey hair assessments confirmed the presence of experimental ischaemia. Women rated the intensity of menstrual and ischaemic pain on a 100-mm visual analogue scale. Women with dysmenorrhoea [mean (SD): 68 (20) mm] reported significantly greater menstrual pain compared with controls [mean (SD): 2 (6) mm; p = 0.0001] during the menstruation phase. They also rated their forearm ischaemic pain as significantly greater than the controls during the menstruation [dysmenorrhoeics vs. controls mean (SD): 58 (19) mm vs. 31 (21) mm, p menstruation phase and pain-free follicular phase. These findings suggest the presence of long-lasting changes in muscle pain sensitivity in women with dysmenorrhoea. Our findings that dysmenorrhoeic women are hyperalgesic to a clinically relevant, deep-muscle ischaemic pain in areas outside of referred menstrual pain confirm other studies showing long-lasting changes in pain sensitivity outside of the painful period during menstruation. © 2014 European Pain Federation - EFIC®

  5. The pictures of CT scan of gold pneumonitis

    International Nuclear Information System (INIS)

    Taguchi, Yoshio; Iwata, Takekuni; Kuroda, Yasumasa; Sadato, Norihiro; Tanemoto, Kiichiro; Adachi, Kazuhiko.

    1987-01-01

    We experienced two cases of gold pneumonitis and their interesting findings of CT scan. After the cessation of gold salt, both cases were treated with the corticosteroid, resulting in the disappearance of pulmonary manifestations and clearing of shadows on chest roentgenograms. The findings of CT scan on both cases were very interesting. They were the high density shadows along the bronchovascular bundles, the fluffy figures surroundings these shadows and band like shadows reached to the thoracic wall. We considered that each shadows were pathologically compatible with severe exudative changes of interstitial pneumonitis, shrinkage surroundings them and thickness of interlobular septum. (author)

  6. Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Harris, Nicholas; Koppel, Juraj; Zsila, Ferenc; Juhas, Stefan; Il'kova, Gabriela; Kogan, Faina Yurgenzon; Lahmy, Orly; Wildbaum, Gizi; Karin, Nathan; Zhuk, Regina; Gregor, Paul

    2016-04-01

    Elucidate the mechanism of action of the small molecule inhibitor of protein binding to glycosaminoglycans, RX-111 and assay its anti-inflammatory activity in animal models of inflammatory disease. The glycosaminoglycan, heparin, was used in the mechanism of action study of RX-111. Human T lymphocytes and umbilical vein endothelial cells were used to assay the in vitro activity of RX-111. Mouse and rat models of disease were used to assay the anti-inflammatory activity of RX-111 in vivo. Circular dichroism and UV/Vis absorption spectroscopy were used to study the binding of RX-111 to the glycosaminoglycan, heparin. T lymphocyte rolling on endothelial cells under shear flow was used to assay RX-111 activity in vitro. Delayed-type hypersensitivity (DTH) and tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in mice and experimental autoimmune encephalomyelitis (EAE) in rats were used to assay anti-inflammatory activity of RX-111 in vivo. RX-111 was shown to bind directly to heparin. It inhibited leukocyte rolling on endothelial cells under shear flow and reduced inflammation in the mouse model of DTH. RX-111 was efficacious in the mouse model of inflammatory bowel disease, TNBS-induced colitis and the rat model of multiple sclerosis, EAE. RX-111 exercises its broad spectrum anti-inflammatory activity by a singular mechanism of action, inhibition of protein binding to the cell surface GAG, heparan sulfate. RX-111 and related thieno[2,3-c]pyridine derivatives are potential therapeutics for the treatment of inflammatory and autoimmune diseases.

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

    Directory of Open Access Journals (Sweden)

    Yuki Nakajima

    2016-02-01

    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.

  8. 355-nm hypersensitization of optical fibers

    NARCIS (Netherlands)

    Canagasabey, A.; Canning, J.; Groothoff, N.

    2003-01-01

    A study is presented on 355-nm hypersensitization of optical fibers. It is found that the intrinsic 244-nm photosensitivity of boron-codoped germanosilicate optical fibers is enhanced by 355-nm hypersensitization. Hypersensitization through standard polymer coating is also demonstrated.

  9. [Sirolimus associated pneumonitis in a hematopoietic stem cell transplant patient].

    Science.gov (United States)

    García, Estefanía; Buenasmañanas, Diana; Martín, Carmen; Rojas, Rafael

    2015-07-06

    Sirolimus (SR) is a lipophilic macrocytic lactone with immunosuppressive properties (mTOR inhibitor) commonly used in solid organ transplantation and recently introduced in the prophylaxis and treatment of graft-versus-host disease. Its numerous side effects include: hyperlipidemia, arthralgias, noncardiac peripheral edema, thrombotic microangiopathy and interstitial pneumonitis. SR-associated pneumonitis is a rare but potentially serious complication due to its increasing utilization in transplant patients. We report the case of a patient undergoing hematopoietic stem cell transplantation with severe respiratory distress and SR therapy. Microbiological tests were all negative and other complications related to transplantation were discarded. The chest computed tomography of high-resolution showed pneumonitis. The SR therapy was interrupted and treatment was started with steroids with resolution of symptoms. SR associated pneumonitis is a potentially fatal side effect. In patients treated with SR and respiratory failure, we must suspect this complication because early recognition along with drug discontinuation and steroid treatment is essential to reverse this complication. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  10. Radiation dermatitis and pneumonitis following breast conserving therapy

    International Nuclear Information System (INIS)

    Yoden, Eisaku; Hiratsuka, Junichi; Imajo, Yoshinari

    2000-01-01

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

  11. Recall lung pneumonitis due to carmustine after radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, P.S.; Geddes, D.M. [Royal Brompton Hospital, London (United Kingdom). Dept. of Respiratory Medicine; Agrawal, S.; Gore, M. [Royal Marsden Hospital, London (United Kingdom)

    1995-10-01

    A patient who developed pneumonitis immediately after the administration of carmustine (BCNU), within exactly the same field as previous irradiation, is presented. The patient responded partially to corticosteroids. This case suggests that irradiation causes subclinical sensitisation of the lung and can therefore have an additive effect in precipitating lung damage when another pulmonary toxin is encountered at a later date. (Author).

  12. [Anticonvulsant hypersensitivity syndrome and lamotrigine-associated anticonvulsant hypersensitivity syndrome].

    Science.gov (United States)

    Taillia, H; Alla, P; Fournier, B; Bounolleau, P; Ouologem, M; Ricard, D; Sallansonnet-Froment, M; de Greslan, T; Renard, J-L

    2009-10-01

    Anticonvulsant hypersensitivity syndrome (AHS) is defined by the association of high fever, cutaneous rash and multiorgan-system abnormalities (incidence, one in 1000 to one in 10,000 exposures). Fatal complications are described in 10%. This reaction usually develops 1 to 12 weeks after initiation of an aromatic anticonvulsant. Drug rash with eosinophilia and systemic symptoms (DRESS) can be discussed as differential diagnosis. Several hypotheses have been put forward to explain the pathogenesis of AHS. These include accumulation of toxic metabolites, antibody production and viral infection. The one based on toxic metabolites has found the greatest acceptance due to the fact that it can be proven by an in vitro test, the lymphocyte toxicity assay. In vivo, skin biopsies show characteristic findings of erythema multiform or typical leucocytoclastic angitis. The patch-test is positive in 80% of the cases. Lamotrigine-associated anticonvulsant hypersensitivity syndrome (LASH) is rare and was described in 1998. We report two new cases demonstrating the two particular configurations of apparition of LASH found in the 14 cases from the review of literature (Pubmed: anticonvulsant hypersensitivity syndrome - lamotrigine): high doses of lamotrigine (or lamotrigine in very young or old patients), and lamotrigine associated with another anti-epileptic (phenobarbital or sodium valproate). We discuss the links between DRESS after lamotrigine and LASH as illustrated in a new case.

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

    Science.gov (United States)

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

    2015-12-01

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

  14. Electromagnetic hypersensitivity: Fact or fiction?

    International Nuclear Information System (INIS)

    Genuis, Stephen J.; Lipp, Christopher T.

    2012-01-01

    As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home or workplace; others suggest that electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various organizations including the World Health Organization as well as some nation states are carefully exploring this clinical phenomenon in order to better explain the rising prevalence of non-specific, multi-system, often debilitating symptoms associated with non-ionizing EMR exposure. As well as an assortment of physiological complaints, patients diagnosed with EHS also report profound social and personal challenges, impairing their ability to function normally in society. This paper offers a review of the sparse literature on this perplexing condition and a discussion of the controversy surrounding the legitimacy of the EHS diagnosis. Recommendations are provided to assist health professionals in caring for individuals complaining of EHS. - Highlights: ► Many people report symptoms when near devices emanating electromagnetic fields(EMF). ► Electromagnetic hypersensitivity (EHS) research has generated conflicting outcomes. ► Recent evidence suggests pathophysiological change in some individuals with EHS. ► EHS patients consistently report profound social and personal challenges. ► Clinicians need to be apprised of the EHS condition and potential interventions.

  15. Climate hypersensitivity to solar forcing?

    Directory of Open Access Journals (Sweden)

    W. Soon

    2000-05-01

    Full Text Available We compare the equilibrium climate responses of a quasi-dynamical energy balance model to radiative forcing by equivalent changes in CO2, solar total irradiance (Stot and solar UV (SUV. The response is largest in the SUV case, in which the imposed UV radiative forcing is preferentially absorbed in the layer above 250 mb, in contrast to the weak response from global-columnar radiative loading by increases in CO2 or Stot. The hypersensitive response of the climate system to solar UV forcing is caused by strongly coupled feedback involving vertical static stability, tropical thick cirrus ice clouds and stratospheric ozone. This mechanism offers a plausible explanation of the apparent hypersensitivity of climate to solar forcing, as suggested by analyses of recent climatic records. The model hypersensitivity strongly depends on climate parameters, especially cloud radiative properties, but is effective for arguably realistic values of these parameters. The proposed solar forcing mechanism should be further confirmed using other models (e.g., general circulation models that may better capture radiative and dynamical couplings of the troposphere and stratosphere.Key words: Meteorology and atmospheric dynamics (climatology · general or miscellaneous · Solar physics · astrophysics · and astronomy (ultraviolet emissions

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

    Directory of Open Access Journals (Sweden)

    Supriya Sarkar

    2012-01-01

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

  17. Biodefense-driven murine model of pneumonic melioidosis.

    Science.gov (United States)

    Jeddeloh, J A; Fritz, D L; Waag, D M; Hartings, J M; Andrews, G P

    2003-01-01

    A whole-body mouse model of pneumonic melioidosis was established for future evaluation of biodefense vaccine candidates. The aerosol 50% lethal doses of Burkholderia pseudomallei strain 1026b for BALB/c and C57BL/6 mice and the times to death, dissemination in organs, and tissue loads after exposure of the mice to low- and high-dose aerosols are reported. In addition, rpsL mutant backgrounds were attenuated in this acute model of disease.

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

    International Nuclear Information System (INIS)

    Olsen, Oeystein E.; Owens, Catherine M.; Sebire, Neil J.; Jaffe, Adam

    2004-01-01

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

  19. Protective effect of corticosteroids on radiation pneumonitis in mice

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  20. Pneumonitis and pneumonitis-related death in cancer patients treated with programmed cell death-1 inhibitors: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Cui P

    2017-09-01

    Full Text Available Peng-Fei Cui,1–3,* Jun-Xun Ma,1,* Fei-Xue Wang,1,* Jing Zhang,1 Hai-Tao Tao,1 Yi Hu1 1First Department of Medical Oncology, 2Department of Graduate Administration, Chinese PLA General Hospital, Beijing, 3Health Bureau of the 75709 Army, Central Theater of the Chinese PLA, Wuhan, China *These authors contributed equally to this work Purpose: We conducted a meta-analysis of published clinical trials to determine the relationship between the risks of pneumonitis and pneumonitis-related death and programmed cell death-1 (PD-1 inhibitor treatment in patients with cancer.Materials and methods: We examined clinical trials from the Medline and Google Scholar databases. Data from original studies and review articles were also cross-referenced and evaluated. Randomized Phase II and Phase III trials of pembrolizumab and nivolumab treatment in patients with cancer were eligible for the analysis. Information about the participants, all-grade and high-grade pneumonitis, and pneumonitis-related death was extracted from each study and analyzed.Results: After the exclusion of ineligible studies, 12 clinical trials were included in the analysis. The odds ratio (OR for all-grade pneumonitis after PD-1 inhibitor treatment was 4.59 (95% confidence interval [CI]: 2.51–8.37; P<0.00001, and the OR for high-grade pneumonitis after PD-1 inhibitor treatment was 3.83 (95% CI: 1.54–9.48; P=0.004. The OR for pneumonitis-related death after PD-1 inhibitor treatment was 2.47 (95% CI: 0.41–14.81; P=0.32. Moreover, the OR for all-grade pneumonitis after nivolumab/ipilimumab combination therapy versus nivolumab monotherapy was 3.54 (95% CI: 1.52–8.23; P=0.003, and that for high-grade pneumonitis after nivolumab/ipilimumab combination therapy versus nivolumab monotherapy was 2.35 (95% CI: 0.45–12.13; P=0.31. Treated cancer appeared to have no effect on the risk of pneumonitis.Conclusion: Our data showed that PD-1 inhibitors were associated with increased risks of all

  1. Improved reactive nanoparticles to treat dentin hypersensitivity.

    Science.gov (United States)

    Toledano-Osorio, Manuel; Osorio, Estrella; Aguilera, Fátima S; Luis Medina-Castillo, Antonio; Toledano, Manuel; Osorio, Raquel

    2018-05-01

    The aim of this study was to evaluate the effectiveness of different nanoparticles-based solutions for dentin permeability reduction and to determine the viscoelastic performance of cervical dentin after their application. Four experimental nanoparticle solutions based on zinc, calcium or doxycycline-loaded polymeric nanoparticles (NPs) were applied on citric acid etched dentin, to facilitate the occlusion and the reduction of the fluid flow at the dentinal tubules. After 24 h and 7 d of storage, cervical dentin was evaluated for fluid filtration. Field emission scanning electron microscopy, energy dispersive analysis, AFM and Nano-DMA analysis were also performed. Complex, storage, loss modulus and tan delta (δ) were assessed. Doxycycline-loaded NPs impaired tubule occlusion and fluid flow reduction trough dentin. Tubules were 100% occluded in dentin treated with calcium-loaded NPs or zinc-loaded NPs, analyzed at 7 d. Dentin treated with both zinc-NPs and calcium-NPs attained the highest reduction of dentinal fluid flow. Moreover, when treating dentin with zinc-NPs, complex modulus values attained at intertubular and peritubular dentin were higher than those obtained after applying calcium-NPs. Zinc-NPs are then supposed to fasten active dentin remodeling, with increased maturity and high mechanical properties. Zinc-based nanoparticles are then proposed for effective dentin remineralization and tubular occlusion. Further research to finally prove for clinical benefits in patients with dentin hypersensitivity using Zn-doped nanoparticles is encouraged. Erosion from acids provokes dentin hypersensitivity (DH) which presents with intense pain of short duration. Open dentinal tubules and demineralization favor DH. Nanogels based on Ca-nanoparticles and Zn-nanoparticles produced an efficient reduction of fluid flow. Dentinal tubules were filled by precipitation of induced calcium-phosphate deposits. When treating dentin with Zn-nanoparticles, complex modulus

  2. Electromagnetic hypersensitivity: Fact or fiction?

    Energy Technology Data Exchange (ETDEWEB)

    Genuis, Stephen J., E-mail: sgenuis@ualberta.ca [University of Alberta (Canada); Lipp, Christopher T. [Faculty of Medicine at the University of Calgary (Canada)

    2012-01-01

    As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home or workplace; others suggest that electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various organizations including the World Health Organization as well as some nation states are carefully exploring this clinical phenomenon in order to better explain the rising prevalence of non-specific, multi-system, often debilitating symptoms associated with non-ionizing EMR exposure. As well as an assortment of physiological complaints, patients diagnosed with EHS also report profound social and personal challenges, impairing their ability to function normally in society. This paper offers a review of the sparse literature on this perplexing condition and a discussion of the controversy surrounding the legitimacy of the EHS diagnosis. Recommendations are provided to assist health professionals in caring for individuals complaining of EHS. - Highlights: Black-Right-Pointing-Pointer Many people report symptoms when near devices emanating electromagnetic fields(EMF). Black-Right-Pointing-Pointer Electromagnetic hypersensitivity (EHS) research has generated conflicting outcomes. Black-Right-Pointing-Pointer Recent evidence suggests pathophysiological change in some individuals with EHS. Black-Right-Pointing-Pointer EHS patients consistently report profound social and personal challenges. Black-Right-Pointing-Pointer Clinicians need to be apprised of the EHS condition and potential interventions.

  3. Amalgam Contact Hypersensitivity Lesion: An Unusual Presentation ...

    African Journals Online (AJOL)

    Contact allergic reactions due to hypersensitivity to dental materials in professionals and ... Keywords: Amalgam, Amalgam contact hypersensitivity lesion, Lichenoid reaction, Oral mucosa ... was associated with mild burning sensation. The patient did ... OLLD in which oral and/or skin lesions appear in temporal association ...

  4. Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Penttilä, P; Donskov, F; Rautiola, J

    2017-01-01

    BACKGROUND: Mammalian target of rapamycin inhibitors may induce pneumonitis. We analysed the association of pneumonitis with outcomes in everolimus treated metastatic renal cell carcinoma (mRCC) patients. PATIENTS AND METHODS: Eighty-five mRCC patients received everolimus at Helsinki University...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

    Vogelius, Ivan R; Bentzen, Søren M

    2012-01-01

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

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

    OpenAIRE

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

    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 ...

  8. Hypersensitivity reactions in patients receiving hemodialysis.

    Science.gov (United States)

    Butani, Lavjay; Calogiuri, Gianfranco

    2017-06-01

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

  9. Hypersensitive transition spectrum of f-element and coordination structure

    International Nuclear Information System (INIS)

    Cao Xuan; Song Chongli; Zhu Youngjun

    1992-10-01

    Some f-f transitions of Ln(An) metallic ions have particular super-sensitivity to the change of coordination environments. This is called super-sensitive transitions. Based on the irreducible tensor operator method, a computation model and corresponding computer program for calculating the hypersensitive transition spectrum of f-element were developed. By comparing the theoretical spectra of all possible coordination structures with experimental one, the possible coordination structures of complex can be determined. The coordination structures of Nd 3+ , Er 3 + hydrate and their extraction complex with H(DEHP) were successfully determined by this method, and the experimental spectra were also assigned

  10. Hypersensitivity to contrast media and dyes.

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Cutaneous drug hypersensitivity : Immunological and genetic perspective

    Directory of Open Access Journals (Sweden)

    Kisalay Ghosh

    2011-01-01

    Full Text Available Drug hypersensitivity is an unpredictable, immunologically mediated adverse reaction, clustered in a genetically predisposed individual. The role of "hapten concept" in immune sensitization has recently been contested by the "pharmacological interaction" hypothesis. After completion of the "human genome project" and with the availability of high-resolution genotyping, genetic susceptibility to hypersensitivity for certain drugs has been proved beyond doubt though the trend is ethnicity and phenotype dependent. Application of this newly acquired knowledge may reduce or abolish the morbidity and mortality associated with cutaneous drug hypersensitivity.

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

    Directory of Open Access Journals (Sweden)

    Corey A. Carter

    2016-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  14. Immediate-type hypersensitivity to polyethylene glycols

    DEFF Research Database (Denmark)

    Wenande, E; Garvey, L H

    2016-01-01

    Polyethylene glycols (PEGs) or macrogols are polyether compounds widely used in medical and household products. Although generally considered biologically inert, cases of mild to life-threatening immediate-type PEG hypersensitivity are reported with increasing frequency. Nevertheless, awareness...

  15. Visceral pain hypersensitivity in functional gastrointestinal disorders.

    Science.gov (United States)

    Farmer, A D; Aziz, Q

    2009-01-01

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

  16. The measurements of plasma cytokines in radiation-induced pneumonitis in lung cancer patients

    International Nuclear Information System (INIS)

    Hur, Won Joo; Youn, Seon Min; Lee, Hyung Sik; Yang, Kwang Mo; Sin, Geun Ho; Son, Choon Hee; Han, Jin Yeong; Lee, Ki Nam; Jeong, Min Ho

    2000-01-01

    To investigate whether changes in plasma concentrations of transforming growth factor-β 1(TGF-β 1), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (lL -6) could be used to identify the development of radiation-induced pneumonitis in the lung cancer patients. Seventeen patients with lung cancer (11 NSCLC. 6 SCLC) were enrolled in a prospective study designed to evaluate clinical and molecular biologic correlation of radiation-induced pneumonitis. The study began in May 1998 and completed in July 1999. All patients were treated with radiotherapy with curative intent: 1.8 Gy per day, 5 fractions per week. Serial measurements of plasma TGF-β1, TNF--α and IL -6 were obtained in all patients before, weekly during radiotherapy and at each follow-up visits after completion of treatment. These measurements were quantified using enzyme linked immunosorbent assay (ELISA). All patients were evaluated for signs and symptoms of pneumonitis at each follow-up visits after completion of radiotherapy. High resolution CT (HRCT) scans were obtained when signs and symptoms of pneumonitis were developed after completion of radiotherapy. Thirteen patients eventually developed signs and symptoms of clinical pneumonitis while four patients did not. TGF- P 1 levels were elevated in - all 13 patients with pneumonitis, which showed characteristic pattern of elevation (38.45 ng/ml at pretreatment, 13.66 ng/ml during radiotherapy, then 60.63 ng/ml at 2-4 weeks after completion of radiotherapy). The levels of TNF--α and IL -6 were also elevated in the group of patients who developed pneumonitis but the pattern was not characteristic. Changes in plasma TGFβ-1 levels before, during and after radiotherapy appears to be a useful means by which to identify patients at risk for the development of symptomatic pneumonitis. Other cytokines like TNF--α and IL-6 shows no meaningful changes in association with radiation pneumonitis

  17. Classification and pathophysiology of radiocontrast media hypersensitivity.

    Science.gov (United States)

    Brockow, Knut; Ring, Johannes

    2010-01-01

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

  18. Radiation pneumonitis in a patient exposed to asbestos

    International Nuclear Information System (INIS)

    Ashford, R.F.U.; Maher, J.; Drury, A.; Pickering, D.

    1981-01-01

    A case report is presented of a 58 year old man who had for many years run an asbestos importing and fibreizing plant. He developed radiation pneumonitis following radiotherapy to a squamous cell carcinoma of the middle 3rd of the oesophagus. Detailed lung studies at autopsy revealed asbestos bodies associated with macrophages in many alveoli and areas of subpleural fibrosis typical of asbestos exposure. This was the most florid case of radiation seen in the Westminster Hospital for some years and the first seen in patients treated for carcinoma of the oesophagus using a three field technique. It is suggested that when planning radiotherapy to an asbestos-exposed patient, a possible increase in lung sensitivity to radiation should be considered when planning dosage. (U.K.)

  19. Simultaneous interstitial pneumonitis and cardiomyopathy induced by venlafaxine

    Directory of Open Access Journals (Sweden)

    Pedro Gonçalo Ferreira

    2014-06-01

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

  20. Incidence of hypersensitivity and anaphylaxis with sugammadex.

    Science.gov (United States)

    Min, K Chris; Woo, Tiffany; Assaid, Christopher; McCrea, Jacqueline; Gurner, Deborah M; Sisk, Christine McCrary; Adkinson, Franklin; Herring, W Joseph

    2018-06-01

    To evaluate the incidence of hypersensitivity and anaphylaxis after administration of sugammadex. Retrospective analysis. Sugammadex clinical development program and post-marketing experience. Surgical patients and healthy volunteers who received sugammadex or placebo/comparator with anesthesia and/or neuromuscular blockade (NMB). Sugammadex administered as 2.0 mg/kg at reappearance of the second twitch, 4.0 mg/kg at 1-2 post-tetanic count, or 16.0 mg/kg at 3 min after rocuronium 1.2 mg/kg. Three analytical methods were used: 1) automated MedDRA queries; 2) searches of adverse events (AEs) consistent with treatment-related hypersensitivity reactions as diagnosed by the investigator; and 3) a retrospective adjudication of AEs suggestive of hypersensitivity by a blinded, independent adjudication committee (AC). In addition, a search of all post-marketing reports of events of hypersensitivity was performed, and events were retrospectively adjudicated by an independent AC. Anaphylaxis was determined according to Sampson Criterion 1. The pooled dataset included 3519 unique subjects who received sugammadex and 544 who received placebo. The automated MedDRA query method showed no apparent increase in hypersensitivity or anaphylaxis with sugammadex as compared to placebo or neostigmine. Similarly, there was a low overall incidence of AEs of treatment-related hypersensitivity (sugammadex and placebo or neostigmine. Finally, the retrospective adjudication of AEs suggestive of hypersensitivity showed a low incidence of hypersensitivity (0.56% and 0.21% for sugammadex 2 mg/kg and 4 mg/kg, respectively), with an incidence similar to subjects who received placebo (0.55%). There were no confirmed cases of anaphylaxis in the pooled studies. During post-marketing use, spontaneous reports of anaphylaxis occurred with approximately 0.01% of sugammadex doses. Subjects who received sugammadex with general anesthesia and/or NMB had a low overall incidence of

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

    LENUS (Irish Health Repository)

    Morcos, A

    2012-06-01

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

  2. [Human herpesvirus-6 pneumonitis following autologous peripheral blood stem cell transplantation].

    Science.gov (United States)

    Saitoh, Yuu; Gotoh, Moritaka; Yoshizawa, Seiichiro; Akahane, Daigo; Fujimoto, Hiroaki; Ito, Yoshikazu; Ohyashiki, Kazuma

    2018-01-01

    A-46-year-old man was diagnosed with peripheral T cell lymphoma, not otherwise specified. He achieved a complete remission after pirarubicin, cyclophosphamide, vincristine, and prednisolone (THP-COP) therapy and successful autologous peripheral blood stem-cell transplantation (AutoSCT). However, 6 months post AutoSCT, he complained of fever. Chest computed tomography of the patient displayed bilateral interstitial pneumonitis. Human herpesvirus-6 (HHV-6) DNA was detected in his bronchoalveolar lavage fluid. Therefore, the patient was confirmed for HHV-6 pneumonitis. The treatment with foscarnet was effective, and no relapse was noticed in the patient. Besides, we have experienced pneumonitis of unknown origin in some patients after autologous or allogeneic stem-cell transplantations. Moreover, most of the above patients were clinically diagnosed using serum or plasma markers. Therefore, examining respiratory symptoms after AutoSCT would enable a more accurate diagnosis as well as treatment of patients with HHV-6 pneumonitis.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-08-01

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

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

    International Nuclear Information System (INIS)

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

    1988-01-01

    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

  5. Diclofenac hypersensitivity: antibody responses to the parent drug and relevant metabolites.

    Directory of Open Access Journals (Sweden)

    Andrea Harrer

    2010-10-01

    Full Text Available Hypersensitivity reactions against nonsteroidal antiinflammatory drugs (NSAIDs like diclofenac (DF can manifest as Type I-like allergic reactions including systemic anaphylaxis. However, except for isolated case studies experimental evidence for an IgE-mediated pathomechanism of DF hypersensitivity is lacking. In this study we aimed to investigate the possible involvement of drug- and/or metabolite-specific antibodies in selective DF hypersensitivity.DF, an organochemically synthesized linkage variant, and five major Phase I metabolites were covalently coupled to carrier proteins. Drug conjugates were analyzed for coupling degree and capacity to crosslink receptor-bound IgE antibodies from drug-sensitized mice. With these conjugates, the presence of hapten-specific IgE antibodies was investigated in patients' samples by ELISA, mediator release assay, and basophil activation test. Production of sulfidoleukotrienes by drug conjugates was determined in PBMCs from DF-hypersensitive patients. All conjugates were shown to carry more than two haptens per carrier molecule. Immunization of mice with drug conjugates induced drug-specific IgE antibodies capable of triggering mediator release. Therefore, the conjugates are suitable tools for detection of drug-specific antibodies and for determination of their anaphylactic activity. Fifty-nine patients were enrolled and categorized as hypersensitive either selectively to DF or to multiple NSAIDs. In none of the patients' samples evidence for drug/metabolite-specific IgE in serum or bound to allergic effector cells was found. In contrast, a small group of patients (8/59, 14% displayed drug/metabolite-specific IgG.We found no evidence for an IgE-mediated effector mechanism based on haptenation of protein carriers in DF-hypersensitive patients. Furthermore, a potential involvement of the most relevant metabolites in DF hypersensitivity reactions could be excluded.

  6. Entomologic evaluation of insect hypersensitivity in horses.

    Science.gov (United States)

    Greiner, E C

    1995-04-01

    Potential methods of incriminating insects as the cause of insect hypersensitivity are presented. A listing of the biting midges known to attack horses in North America is presented also. An example of how species may be determined to be the cause of the hypersensitivity is given using data from a recent study in Florida. Light trap collections indicated the temporal and geographic distribution of potential contributing species and collections made by vacuuming horses further delineated species by proving they feed on horses and the correct locations on the horses to match lesion distribution. Culicoides hypersensitivity in horses in Florida seems to be caused by a series of species active and feeding on the horses at different times of the year.

  7. Drug hypersensitivity in clonal mast cell disorders

    DEFF Research Database (Denmark)

    Bonadonna, P; Pagani, M; Aberer, W

    2015-01-01

    and severity of immediate hypersensitivity reactions. Mastocytosis in adults is associated with a history of anaphylaxis in 22-49%. Fatal anaphylaxis has been described particularly following hymenoptera stings, but also occasionally after the intake of drugs such as nonsteroidal anti-inflammatory drugs......, opioids and drugs in the perioperative setting. However, data on the frequency of drug hypersensitivity in mastocytosis and vice versa are scarce and evidence for an association appears to be limited. Nevertheless, clonal MC disorders should be ruled out in cases of severe anaphylaxis: basal serum...... tryptase determination, physical examination for cutaneous mastocytosis lesions, and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC...

  8. Hypersensitivity Reactions from Excipients in Systemic Glucocorticoid Formulations

    DEFF Research Database (Denmark)

    Calogiuri, Gianfranco; Garvey, Lene H; Romita, Paolo

    2016-01-01

    Glucocorticoids are the most widely used drugs for the treatment of hypersensitivity, however these drugs themselves and the excipients contained in commercial corticosteroid formulations are able to induce severe immediate-type hypersensitivity reactions. Reactions involving excipients have been...

  9. Heart irradiation as a risk factor for radiation pneumonitis

    International Nuclear Information System (INIS)

    Huang, Ellen X.; El Naqa, Issam; Deasy, Joseph O.; Bradley, Jeffrey D.; Hope, Andrew J.; Lindsay, Patricia E.; Trovo, Marco

    2011-01-01

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

  10. Sirolimus-associated interstitial pneumonitis in a liver transplant recipient

    International Nuclear Information System (INIS)

    Claire Berrouet, Marie; Aristizabal, Julian Miguel; Restrepo, Juan Carlos; Correa, Gonzalo

    2005-01-01

    Sirolimus is an immunosuppressive drug that has been used during the past few years. Sirolimus is indicated in rescue therapies and to reduce the secondary toxic effects of calcineurin inhibitors. This drug has been associated with infrequent but severe pulmonary toxicity. Cases of interstitial pneumonitis, bronchiolitis obliterans with organizing pneumonia, and alveolar proteinosis have been described. We describe a case of pulmonary toxicity associated with the use of sirolimus in a 59-yr-old liver transplant recipient. We also review all reported cases of sirolimus-associated lung toxicity among liver transplantation recipients, with the intention of understanding the risk factors, the clinical picture and the outcomes of this complication. Five cases have been reported since January 2000, including the present case. Clinical presentation is similar, with fever, dyspnoea, fatigue, cough, and hemoptysis. Discontinuation of the drug led to resolution of clinical and radiographic findings. Sirolimus-induced pulmonary toxicity is a serious condition and should be considered in the differential diagnosis of liver recipients presenting with respiratory findings. Discontinuation of the drug is associated with resolution of the pulmonary compromise

  11. The Dapsone Hypersensitivity Syndrome revisited: a potentially fatal multisystem disorder with prominent hepatopulmonary manifestations

    Directory of Open Access Journals (Sweden)

    Chi David S

    2006-06-01

    Full Text Available Abstract 4,4'-Diaminodiphenylsulphone (Dapsone is widely used for a variety of infectious, immune and hypersensitivity disorders, with indications ranging from Hansen's disease, inflammatory disease and insect bites, all of which may be seen as manifestations in certain occupational diseases. However, the use of dapsone may be associated with a plethora of adverse effects, some of which may involve the pulmonary parenchyma. Methemoglobinemia with resultant cyanosis, bone marrow aplasia and/or hemolytic anemia, peripheral neuropathy and the potentially fatal dapsone hypersensitivity syndrome (DHS, the focus of this review, may all occur individually or in combination. DHS typically presents with a triad of fever, skin eruption, and internal organ (lung, liver, neurological and other systems involvement, occurring several weeks to as late as 6 months after the initial administration of the drug. In this sense, it may resemble a DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms. DHS must be promptly identified, as untreated, the disorder could be fatal. Moreover, the pulmonary/systemic manifestations may be mistaken for other disorders. Eosinophilic infiltrates, pneumonitis, pleural effusions and interstitial lung disease may be seen. This syndrome is best approached with the immediate discontinuation of the offending drug and prompt administration of oral or intravenous glucocorticoids. An immunological-inflammatory basis of the syndrome can be envisaged, based on the pathological picture and excellent response to antiinflammatory therapy. Since dapsone is used for various indications, physicians from all specialties may encounter DHS and need to familiarize themselves with the salient features about the syndrome and its management.

  12. Dentine hypersensitivity: real or imagined | Gbadebo | Nigerian ...

    African Journals Online (AJOL)

    Background: Dentine hypersensitivity is a common presentation of cause of pain and or discomfort with mastication which has been shown to affect the quality of life of the affected individual. It is also a common cause of presentation at the dental clinics. However, the cause, diagnosis and possible management to give relief ...

  13. Tuberculous Lymphadenitis: Skin Delayed-Type Hypersensitivity ...

    African Journals Online (AJOL)

    Tuberculous Lymphadenitis: Skin Delayed-Type Hypersensitivity Reaction and Cellular Immune Responses. ... The tuberculin skin test (TST) and peripheral blood mono-nuclear cells (PBMCs) culture were conducted using PPD. The cytokines were measured using commercial kits. Results: The mean TST was 24.6 ±8.0 ...

  14. Investigation of Seminal Plasma Hypersensitivity Reactions

    Science.gov (United States)

    1998-10-01

    diseases, chronic vaginal candidiasis ); 3) establish the prevalence of BSS and localized/systemic seminal plasma protein hypersensitivity among the GW...of further investigation as our population grows. Subsequent pharmacologic treatment of this female for chronic vaginal candidiasis with an...partner.2Ř Subsequently, women experiencing localized vaginal inflammation, characterized by burning and pain and occurring immediately after contact

  15. Severe Hyperacusis, Photophobia, and Skin Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Alessandra Barbara Fioretti

    2016-01-01

    Full Text Available 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.

  16. Factors predicting radiation pneumonitis in locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Kim, Myung Soo; Lee, Ji Hae; Ha, Bo Ram; Lee, Re Na

    2011-01-01

    Thoracic radiotherapy is a major treatment modality of stage III non-small cell lung cancer. The normal lung tissue is sensitive to radiation and radiation pneumonitis is the most important dose-limiting complication of thoracic radiation therapy. This study was performed to identify the clinical and dosimetric parameters related to the risk of radiation pneumonitis after definitive radiotherapy in stage III non-small cell cancer patients. The medical records were reviewed for 49 patients who completed definitive radiation therapy for locally advanced non-small cell lung cancer from August 2000 to February 2010. Radiation therapy was delivered with the daily dose of 1.8 Gy to 2.0 Gy and the total radiation dose ranged from 50.0 Gy to 70.2 Gy (median, 61.2 Gy). Elective nodal irradiation was delivered at a dose of 45.0 Gy to 50.0 Gy. Seven patients (14.3%) were treated with radiation therapy alone and forty two patients (85.7%) were treated with chemotherapy either sequentially or concurrently. Twenty-five cases (51.0%) out of 49 cases experienced radiation pneumonitis. According to the radiation pneumonitis grade, 10 (20.4%) were grade 1, 9 (18.4%) were grade 2, 4 (8.2%) were grade 3, and 2 (4.1%) were grade 4. In the univariate analyses, no clinical factors including age, sex, performance status, smoking history, underlying lung disease, tumor location, total radiation dose and chemotherapy were associated with grade ≥2 radiation pneumonitis. In the subgroup analysis of the chemotherapy group, concurrent rather than sequential chemotherapy was significantly related to grade ≥2 radiation pneumonitis comparing sequential chemotherapy. In the univariate analysis with dosimetric factors, mean lung dose (MLD), V20, V30, V40, MLDipsi, V20ipsi, V30ipsi, and V40ipsi were associated with grade ≥2 radiation pneumonitis. In addition, multivariate analysis showed that MLD and V30 were independent predicting factors for grade ≥2 radiation pneumonitis. Concurrent

  17. Pathological study about two autopsy cases of bilateral irradiation pneumonitis induced by unilateral irradiation

    International Nuclear Information System (INIS)

    Yamauchi, Noriko; Tajima, Yo; Iio, Masaaki; Oshima, Takeo; Iino, Koichi.

    1978-01-01

    The first case is a 73-year-old man with left lung cancer. Seven days after completion of radiotherapy 7,000 rad, a chest roentgenogram showed diffuse bilateral pneumonia. The second case is a 61-year-old woman with right lung cancer and about one month after completion of radiotherapy 2,600 rad, a chest roentgenogram showed bilateral pneumonia. Pathological findings, all lobes of both lungs of these cases showed acute interstitial pneumonitis. The pathogenesis of irradiation pneumonitis is poorly understood. Several investigators thought that the pathogenesis of irradiation pneumonitis was caused by autoimmune mechanism, they carried out sero-pathological studies and demonstrated the bilateral pneumonia caused by unilateral irradiation. (author)

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Keisuke Imafuku

    2017-04-01

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

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

    International Nuclear Information System (INIS)

    Kocak, Zafer; Borst, Gerben R.; Zeng Jing; Zhou Sumin; Hollis, Donna R.; Zhang Junan; Evans, Elizabeth S.; Folz, Rodney J.; Wong, Terrence; Kahn, Daniel; Belderbos, Jose S.A.; Lebesque, Joos V.; Marks, Lawrence B.

    2007-01-01

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

  1. Usefulness of serum KL-6 and SP-D in the diagnosis of radiation pneumonitis

    International Nuclear Information System (INIS)

    Saika, Yoshinori; Doi, Kenji; Misaki, Toshimasa; Tatsumi, Tomoaki; Komori, Tsuyoshi; Narabayashi, Isamu

    2004-01-01

    The objective of this study was to investigate the usefulness of serum KL-6 and SP-D in the diagnosis of radiation pneumonitis. We measured serum KL-6 and SP-D in patients undergoing radiation therapy of the chest, primarily for lung cancer, in the Department of Radiology, Osaka Medical College and compared the results with the findings on plain chest X-ray films and thoracic computed tomography conducted at the same time. The sensitivity of serum KL-6 and SP-D for diagnosing radiation pneumonitis were 68.2% and 70.0%, respectively, the specificity were 86.6% and 80.0%, and the accuracy were 82.0% and 77.8%. Examination of the relationship between lesion extent and activity and serum KL-6 showed that serum KL-6 values were higher when the lesion extended beyond the irradiation field than when the lesion was confined to within the irradiation field and that the value tended to be lower for old lesions than for active lesions. In patients with radiation pneumonitis in whom serum KL-6 and SP-D could be measured over time, KL-6 tended to increase after the lesion was discovered by imaging, whereas SP-D increased prior to this in many cases. Examination of the comparison between before radiotherapy and just after radiotherapy in the patients with radiation pneumonitis showed that SP-D had a consistent tendency to increase. Both serum KL-6 and SP-D had a satisfactory degree of sensitivity and specificity for diagnosing radiation pneumonitis. Serum KL-6 correlated with the extent and activity of the lesions. The results suggested that serum SP-D may be helpful for the early detection of radiation pneumonitis. (author)

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

    International Nuclear Information System (INIS)

    Tsoutsou, Pelagia G.; Koukourakis, Michael I.

    2006-01-01

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

  3. Concomitant Human Herpes Virus 6 and nivolumab-related pneumonitis: Potential pathogenetic insights

    Directory of Open Access Journals (Sweden)

    Periklis G. Foukas

    2018-01-01

    Full Text Available The development of immune system modulating agents, such as immune checkpoint inhibitors (ICIs, has revolutionized cancer treatment. Nivolumab, a human monoclonal antibody against PD-1, has emerged as an efficient treatment for various malignancies, including non-small cell lung cancer (NSCLC; however, it is associated with important immune related side-effects, attributed to organ-specific inflammation, such as immune-mediated pneumonitis, a relatively uncommon, albeit potentially fatal adverse event. We herein present the unique case of severe interstitial pneumonitis with concomitant detection of Human Herpes Virus 6 (HHV-6 in a nivolumab treated patient with NSCLC. Potential pathogenetic mechanisms are discussed.

  4. Case of immediate hypersensitivity to beer.

    Science.gov (United States)

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

    2016-06-01

    We report here a case of immediate hypersensitivity to beer, in which a female patient developed angioedema of the eyelids shortly after consuming beer. In skin prick tests, the patient showed positive reactions to the base ingredients of beer, particularly malt and barley. The specific serum immunoglobulin E antibodies against barley and malt displayed weakly positive reactivity. To identify the immunoreactive antigens, malt and barley proteins were separated by 2-D polyacrylamide gel electrophoresis and immunoreacted with the patient's serum. The results of mass spectrometric analysis revealed that the main antigen was a protein with similarity to protein z-type serpin. Notably, the identified antigen had a molecular weight of 20-25 kDa, which is markedly smaller than that previously reported for protein Z4 (44 kDa). Taken together, these analyses indicate that a possible new antigen which belongs to the protein Z family elicits immediate hypersensitivity to beer. © 2015 Japanese Dermatological Association.

  5. 7th drug hypersensitivity meeting: part one

    OpenAIRE

    Carr, Daniel F.; Chung, Wen-Hung; Jenkiins, Rosalind E.; Chaponda, Mas; Nwikue, Gospel; Cornejo Castro, Elena M.; Antoine, Daniel J.; Pirmohamed, Munir; Wuillemin, Natascha; Dina, Dolores; Eriksson, Klara K.; Yerly, Daniel; Pavlos, Rebecca; Mckinnin, Elizabeth; Ostrov, David

    2016-01-01

    Table of contents Oral Abstracts O1 Functionally distinct HMGB1 isoforms correlate with physiological processes in drug-induced SJS/TEN Daniel F. Carr, Wen-Hung Chung, Rosalind E. Jenkiins, Mas Chaponda, Gospel Nwikue, Elena M. Cornejo Castro, Daniel J. Antoine, Munir Pirmohamed O2 Hypersensitivity reactions to beta-lactams, does the t cell recognition pattern influence the clinical picture? Natascha Wuillemin, Dolores Dina, Klara K. Eriksson, Daniel Yerly O3 Specific binding characteristics ...

  6. Dentin Hypersensitivity: Recent Concepts in Management

    Directory of Open Access Journals (Sweden)

    Vijay Mantri

    2011-01-01

    Full Text Available Tooth sensitivity is a very common clinical presentation which can cause considerable concern for patients. Dentin hypersensitivity (DH is characterized by short sharp pain arising from exposed dentin in response to stimuli. The most widely accepted theory of how the pain occurs is Brannstrom′s hydrodynamic theory, fluid movement within the dentinal tubules. The condition generally involves the facial surfaces of teeth near the cervical aspect and is very common in premolars and canines. This condition is frequently encountered by dentists, periodontists, hygienists and dental therapists. Some dental professionals lack confidence in treating DH. The management of this condition requires a good understanding of the complexity of the problem, as well as the variety of treatments available. This review considers the etiopathogenesis, incidence, diagnosis, prevention and management of dentinal hypersensitivity. DH is diagnosed after elimination of other possible causes of the pain. Any treatment plan for DH should include identifying and eliminating predisposing etiologic factors. Professionals should appreciate the role causative factors play in localizing and initiating hypersensitive lesions. It is important to identify these factors so that prevention can be included in the treatment plan. Treatments can be self-administered by the patient at home or be applied by a dental professional in the dental office. At-home methods tend to be simple and inexpensive and can treat simultaneously generalized DH affecting many teeth Desensitizing treatment should be delivered systematically, beginning with prevention and at-home treatments. The latter may be supplemented with in-office modalities.

  7. Purple sweet potato (Ipomea Batatas P. as dentin hypersensitivity desensitization gel

    Directory of Open Access Journals (Sweden)

    Chariza Hanum Mayvita Iskandar

    2015-12-01

    Full Text Available Background: Dentin hypersensitivity is a short sharp sense of pain in the teeth when exposed to excitatory stimulus. A total of 74% of world population experiencing dentin hypersensitivity. Home treatment topical desensitization is rarely found in Indonesia. The use of dentrifice is less practical because it must be done with regular brushing. Indonesia has abundant natural resources, one of which is purple sweet potato. Purple sweet potato (Ipomea Batatas P. has highest potasium ions compared to other foodstuffs. Potassium ions can be a solution of dentin hypersensitivity by temporary blocking the suffix pulp nerve impulses. Purpose: The research objective was to determine the effectiveness of the 10% purple sweet potato extract gel of the dental pain threshold score. Method: An experimental study carried out by dental pain threshold score measurements using vitality tester into the teeth with gum recession. Samples included 32 respondents with a single blind and pre-post test control group design. They were divided into treatment group and negative control group. Paired T-test and Wilcoxon were used as data analysis. Result: The results showed dental pain threshold score increasing either in treatment group and negative control, although not as significant as in the treatment group. Conclusion: 10% purple sweet potato extract gel containing potassium ions is able to reduce the pain of dentin hypersensitivity.

  8. Dynamics of the pneumonic plague epidemic in Madagascar, August to October 2017.

    Science.gov (United States)

    Tsuzuki, Shinya; Lee, Hyojung; Miura, Fuminari; Chan, Yat Hin; Jung, Sung-Mok; Akhmetzhanov, Andrei R; Nishiura, Hiroshi

    2017-11-01

    Transmission potential and severity of pneumonic plague in Madagascar were assessed. Accounting for reporting delay, the reproduction number was estimated at 1.73. The case fatality risk was estimated as 5.5%. Expected numbers of exported cases from Madagascar were estimated across the world and all estimates were below 1 person from August to October, 2017.

  9. First case of severe pneumonic tularemia in an immunocompetent patient in the Netherlands

    NARCIS (Netherlands)

    Sigaloff, K.C.E.; Chung, P.K.; Koopmans, J.; Notermans, D.W.; Rijckevorsel, Van G.G.C.; Koene, M.; Sprengers, R.W.; Gooskens, J.; Stalenhoef, J.E.

    2017-01-01

    Tularemia is a zoonosis caused by different subspecies of the Gram-negative bacterium Francisella tularensis. We report the first case in the Netherlands of pneumonic tularemia caused by the F. tularensis subspecies holarctica after probable occupational inhalation of contaminated aerosols.

  10. First case of severe pneumonic tularemia in an immunocompetent patient in the Netherlands.

    NARCIS (Netherlands)

    Sigaloff, K C E; Chung, P K; Koopmans, J; Notermans, D W; van Rijckevorsel, G G C; Koene, M; Sprengers, R W; Gooskens, J; Stalenhoef, J E

    Tularemia is a zoonosis caused by different subspecies of the Gram-negative bacterium Francisella tularensis. We report the first case in the Netherlands of pneumonic tularemia caused by the F. tularensis subspecies holarctica after probable occupational inhalation of contaminated aerosols.

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

    International Nuclear Information System (INIS)

    Ogo, Etsuyo; Fujimoto, Kiminori; Hayabuchi, Naofumi

    2002-01-01

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

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

    Science.gov (United States)

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

    2010-09-01

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

  13. Carboplatin hypersensitivity: evaluation and successful desensitization protocol.

    Science.gov (United States)

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

    2014-01-01

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

  14. An unusual oral habit presenting as Dentin Hypersensitivity | Afolabi ...

    African Journals Online (AJOL)

    We present the case of a 30-year-old man with an unusual oral habit- office pin chewing and filing of the front tooth which resulted in dentine hypersensitivity. Clinical relevance: The role of daily oral habits and techniques of cessation were suggested in the management of dentine hypersensitivity. Keywords: Unusual oral ...

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

    Science.gov (United States)

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

    2010-06-01

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

  16. Association between Severity of Tooth Wear and Dentinal Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Ashok Ayer

    2016-11-01

    Full Text Available Background & Objectives: Tooth wear (attrition, abrasion, erosion, and abfraction is perceived globally as ever increasing problem. Several outcome of the tooth wear are hypersensitivity, esthetic problems, functional impairment, annoyance to the patient, and fracture of the tooth. Among these, the measurable and more commonly reported outcome is hypersensitivity to stimuli. Although dentin hypersensitivity is a common clinical condition and is generally reported by the patient after experiencing a sharp, short pain caused by one of the several different external stimuli, it is often inadequately understood. None of the scientific literature available till date attempted to establish the relationship between tooth wear and dentin hypersensitivity which could be a key factor in monitoring those patients.  The aim of the study was to estimate the association between severity of teeth wear and sensitivity in the patients with reported dentinal hypersensitivity.Materials & Methods: Fifty patients with dentin hypersensitivity were investigated for tooth wear. Tooth wear measured using exact tooth wear index and level of sensitivity to stimuli was recorded using a numerical rating scale. Results: Enamel wear at cervical region of teeth showed a positive correlation (p=.010, similarly, dentin wear at cervical region of teeth showed positive correlation and significant association (p<.001 with dentinal hypersensitivity.Conclusion: The observation supports a significant association between severities of tooth surface wear and dentinal hypersensitivity.

  17. Estimation of pneumonitis risk in three-dimensional treatment planning using dose-volume histogram analysis

    International Nuclear Information System (INIS)

    Oetzel, Dieter; Schraube, Peter; Hensley, Frank; Sroka-Perez, Gabriele; Menke, Markus; Flentje, Michael

    1995-01-01

    Purpose: Investigations to study correlations between the estimations of biophysical models in three dimensional (3D) treatment planning and clinical observations are scarce. The development of clinically symptomatic pneumonitis in the radiotherapy of thoracic malignomas was chosen to test the predictive power of Lyman's normal tissue complication probability (NTCP) model for the assessment of side effects for nonuniform irradiation. Methods and Materials: In a retrospective analysis individual computed-tomography-based 3D dose distributions of a random sample of (46(20)) patients with lung/esophageal cancer were reconstructed. All patients received tumor doses between 50 and 60 Gy in a conventional treatment schedule. Biological isoeffective dose-volume histograms (DVHs) were used for the calculation of complication probabilities after applying Lyman's and Kutcher's DVH-reduction algorithm. Lung dose statistics were performed for single lung (involved ipsilateral and contralateral) and for the lung as a paired organ. Results: In the lung cancer group, about 20% of the patients (9 out of 46) developed pneumonitis 3-12 (median 7.5) weeks after completion of radiotherapy. For the majority of these lung cancer patients, the involved ipsilateral lung received a much higher dose than the contralateral lung, and the pneumonitis patients had on average a higher lung exposure with a doubling of the predicted complication risk (38% vs. 20%). The lower lung exposure for the esophagus patients resulted in a mean lung dose of 13.2 Gy (lung cancer: 20.5 Gy) averaged over all patients in correlation with an almost zero complication risk and only one observed case of pneumonitis (1 out of 20). To compare the pneumonitis risk estimations with observed complication rates, the patients were ranked into bins of mean ipsilateral lung dose. Particularly, in the bins with the highest patient numbers, a good correlation was achieved. Agreement was not reached for the lung functioning as

  18. Clinical efficacy of toothpaste containing potassium citrate in treating dentin hypersensitivity

    Directory of Open Access Journals (Sweden)

    Shih-Ya Shen

    2009-12-01

    Conclusion: The prevalence of dentin hypersensitivity in this study was 38%. The use of desensitizing toothpaste containing potassium citrate with oral hygiene instruction can effectively reduce dentin hypersensitivity.

  19. Dentinal hypersensitivity following scaling and root planing: comparison of low-level laser and topical fluoride treatment.

    Science.gov (United States)

    Pesevska, Snezana; Nakova, Marija; Ivanovski, Kiro; Angelov, Nikola; Kesic, Ljiljana; Obradovic, Radmila; Mindova, Sonja; Nares, Salvador

    2010-09-01

    The aim of this study is to compare the effectiveness of low-level laser irradiation to traditional topical fluoride treatment for treatment choices of dentinal hypersensitivity following scaling and root planing. The experimental group (15 patients) was treated with low-energy-level diode laser at each site of dentinal hypersensitivity following scaling and root planning. The control group (15 patients) received topical fluoride treatment (protective varnish for desensitization). All the patients were treated at baseline visit, and then at day 2 and 4 after the initial treatment; the pain was subjectively assessed by the patients as strong, medium, medium low, low, or no pain. Total absence of the dental hypersensitivity was reported in 26.66% of the examined group even after the second visit, compared to the control group where complete resolution of the hypersensitivity was not present after the second visit in any of the treated cases. Complete absence of pain was achieved in 86.6% of patients treated with laser and only in 26.6% in the fluoride treated group, after the third visit. Based on our findings, we conclude that low-energy biostimulative laser treatment can be successfully used for treatment of dental hypersensitivity following scaling and root planing.

  20. A case of severe radiation pneumonitis. A trial of plasma exchange

    International Nuclear Information System (INIS)

    Miyagawa, Tomoko; Mochizuki, Yoshirou; Nakahara, Yasuharu

    2009-01-01

    A 77-year-old man underwent radiotherapy for the squamous cell carcinoma of the right lung. Two months after the 60 Gy/30 fr irradiation was completed, he complained of dyspnea and his chest X-ray showed ground glass opacities and reticular shadows in both lung fields. Severe radiation pneumonitis was diagnosed. Two grams of methylprednisolone did not improve his symptoms and on the next day his hypoxemia worsened. We then tried plasma exchange because of his critical status. His respiratory status improved rapidly after plasma exchange and his chest X-ray showed remarkable improvement 10 days later. We think this case suggests the effectiveness of plasma exchange for severe radiation pneumonitis. (author)

  1. Early host cell targets of Yersinia pestis during primary pneumonic plague.

    Directory of Open Access Journals (Sweden)

    Roger D Pechous

    Full Text Available Inhalation of Yersinia pestis causes primary pneumonic plague, a highly lethal syndrome with mortality rates approaching 100%. Pneumonic plague progression is biphasic, with an initial pre-inflammatory phase facilitating bacterial growth in the absence of host inflammation, followed by a pro-inflammatory phase marked by extensive neutrophil influx, an inflammatory cytokine storm, and severe tissue destruction. Using a FRET-based probe to quantitate injection of effector proteins by the Y. pestis type III secretion system, we show that these bacteria target alveolar macrophages early during infection of mice, followed by a switch in host cell preference to neutrophils. We also demonstrate that neutrophil influx is unable to limit bacterial growth in the lung and is ultimately responsible for the severe inflammation during the lethal pro-inflammatory phase.

  2. Radiation pneumonitis: generalised lung changes detected by radionuclide imaging following focal lung irradiation

    International Nuclear Information System (INIS)

    Ball, D.; Sephton, R.; Irving, L.; Crennan, E.

    1992-01-01

    The usefulness of a nuclear imaging technique as a means of detecting radiation-induced lung injury is examined. The technique involves the patient inhaling modified technegas TM , a gas-like radiotracer which is an ultra fine particulate dispersion. This crosses the alveolar-capillary membrane and the clearance rate of the tracer from the lungs is presumed to reflect membrane permeability. A case of a patient who, after receiving localised radiotherapy and chemotherapy for lung cancer, developed symptoms and signs of radiation pneumonitis is reported. Pre- and post-radiotherapy investigations using the nuclear technique showed acceleration of rates of tracer clearance from both lungs, consistent with generalised changes in alveolar-capillary membrane permeability. It is suggested that the symptoms of radiation pneumonitis may in part result from pathophysiologic changes in nonirradiated lung which may appear radiologically normal. 4 refs., 2 figs

  3. An Extremely Rapid Case of Pneumonitis with the Use of Nivolumab for Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Rubens Barros Costa

    2018-01-01

    Full Text Available Pancreatic cancer is the fourth most common cancer death in the United States despite comprising a small percentage of the total number of cancer cases. The estimated 5-year overall survival (OS for patients with distant metastatic disease is approximately 3%. New treatment options are an unmet need and remain an area of active investigation. A 53-year-old male with metastatic pancreatic cancer presented to the hospital with acute-on-chronic respiratory failure approximately 24 hours after receiving a novel therapeutic combination. Chest imaging showed marked changes as concerning for pneumonitis. Infectious workup was negative. The patient had initial clinical improvement after receiving initial intravenous steroids and oxygen support but eventually deteriorated later opting for supportive measures only. With infection ruled out, drug-induced pneumonitis was felt to be the likely cause of the radiologic and clinical changes. The rapidity of onset of symptoms is the aspect being highlighted in this case.

  4. Correlation factor analysis between radiation pneumonitis and chemo-radiotherapy in breast cancer patients

    International Nuclear Information System (INIS)

    Li Huiping; Wang Junjie; Ma Liwen; Zhang Shulan; Deng Huijing; Jia Tingzhen

    2004-01-01

    Objective: To investigate the relationship between radiotherapy-induced lung injury and chemotherapy agents as well as other factors. Methods: A total of 85 breast cancer patients received radiotherapy with sequential or concurrent chemotherapy after surgery were analysed for radiation dose, chemotherapy schedule, age, and lung disease history. Results: Five patients had clinical symptoms of radiation pneumonitis, one of them was necessary to treat and 16 patients developed radiological changes (18.8%). Close relationship was noted between incidence of radiation pneumonitis and radiation dose, timing and drugs used in chemotherapy and lung disease history. Conclusion: High irradiation dose, concurrent chemotherapy, and lung disease history can increase the rate of radiotherapy-induced pulmonary injury in breast cancer patients. (authors)

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

    Science.gov (United States)

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

    1992-01-01

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

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  7. Inhalational Gentamicin Treatment Is Effective Against Pneumonic Plague in a Mouse Model

    Directory of Open Access Journals (Sweden)

    David Gur

    2018-04-01

    Full Text Available Pneumonic plague is an infectious disease characterized by rapid and fulminant development of acute pneumonia and septicemia that results in death within days of exposure. The causative agent of pneumonic plague, Yersinia pestis (Y. pestis, is a Tier-1 bio-threat agent. Parenteral antibiotic treatment is effective when given within a narrow therapeutic window after symptom onset. However, the non-specific “flu-like” symptoms often lead to delayed diagnosis and therapy. In this study, we evaluated inhalational gentamicin therapy in an infected mouse model as a means to improve antibiotic treatment efficacy. Inhalation is an attractive route for treating lung infections. The advantages include directly dosing the main infection site, the relative accessibility for administration and the lack of extensive enzymatic drug degradation machinery. In this study, we show that inhalational gentamicin treatment administered 24 h post-infection, prior to the appearance of symptoms, protected against lethal intranasal challenge with the fully virulent Y. pestis Kimberley53 strain (Kim53. Similarly, a high survival rate was demonstrated in mice treated by inhalation with another aminoglycoside, tobramycin, for which an FDA-approved inhaled formulation is clinically available for cystic fibrosis patients. Inhalational treatment with gentamicin 48 h post-infection (to symptomatic mice was also successful against a Y. pestis challenge dose of 10 i.n.LD50. Whole-body imaging using IVIS technology demonstrated that adding inhalational gentamicin to parenteral therapy accelerated the clearance of Y. pestis from the lungs of infected animals. This may reduce disease severity and the risk of secondary infections. In conclusion, our data suggest that inhalational therapy with aerosolized gentamicin may be an effective prophylactic treatment against pneumonic plague. We also demonstrate the benefit of combining this treatment with a conventional parenteral

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

    Directory of Open Access Journals (Sweden)

    Anne Derbise

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

  9. Differentiation between endobronchial tuberculosis and bronchogenic carcinoma associated with atelectasis or obstructive pneumonitis: CT evaluation

    International Nuclear Information System (INIS)

    Chung, Hwan Hoon; Oh, Yu Whan; Kim, Kyeong Ah; Kim, Jung Hyuk

    1995-01-01

    Endobronchial tuberculosis and bronchogenic cancer are common causes of atelectasis or obstructive pneumonitis in Korea. Differentiation between endobronchial tuberculosis and bronchogenic carcinoma is important for the treatment and prognosis but it is sometimes difficult to differentiate these two lesions with radiologic examinations. The purpose of this study was to find the differential points between endobronchial tuberculosis and bronchogenic carcinoma associated with atelectasis or obstructive pneumonitis. Forty patients in whom atelectasis or obstructive pneumonitis was detected on chest radiographs comprised the study. A definite mass opacity was not observed on chest radiographs in all patients. In these patients, the causes of obstruction were endobronchial tuberculosis (n = 20) and bronchogenic cancer (n = 20) which were microbiologically or pathologically confirmed. Double obstructive lesions were more frequently found in endobronchial tuberculosis (8/20) than in bronchogenic cancer (1/20). Multiple calcification along the bronchial wall and severe distortion of bronchi were observed only in endobronchial tuberculosis (4/20) and associated low density mass at obstruction site was only observed in bronchogenic cancer (6/20). Bronchial dilatation (11/20) and parenchymal calcifications (14/20) distal to obstruction site, air containing bronchogram at post obstructive bronchus (14/20) were more frequently found in endobronchial tuberculosis. Contour bulging at obstruction site (14/20), and only mucus bronchogram at post obstructive bronchus (14/20) were more frequently found in bronchogenic carcinoma. In patients with atelectasis or obstructive pneumonitis, endobronchial tuberculosis is characterized by double obstructive lesion, multiple calcifications at the bronchial wall, and severe distortion of the bronchi. Endobronchial carcinoma is characterized by a low density mass at the obstructive site

  10. Hypersensitivity to pain in congenital blindness

    DEFF Research Database (Denmark)

    Slimani, Hocine; Danti, Sabrina; Ricciardi, Emiliano

    2013-01-01

    Vision is important for avoiding encounters with objects in the environment that may imperil physical integrity. We tested whether, in the absence of vision, a lower pain threshold would arise from an adaptive shift to other sensory channels. We therefore measured heat and cold pain thresholds an...... that blind subjects are more attentive to signals of external threats. These findings indicate that the absence of vision from birth induces a hypersensitivity to painful stimuli, lending new support to a model of sensory integration of vision and pain processing......., congenitally blind subjects have lower heat pain thresholds, rate suprathreshold heat pain stimuli as more painful, and have increased sensitivity for cold pain stimuli. Thresholds for nonpainful thermal stimulation did not differ between groups. The results of the pain questionnaires further indicated...

  11. Respiratory hypersensitivity reactions to NSAIDs in Europe

    DEFF Research Database (Denmark)

    Makowska, J S; Burney, P; Jarvis, D

    2016-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper...... and lower respiratory tract disorders. METHODS: The GA(2) LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled...... prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants...

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

    Science.gov (United States)

    Tan, Susanna K; Burgener, Elizabeth B; Waggoner, Jesse J; Gajurel, Kiran; Gonzalez, Sarah; Chen, Sharon F; Pinsky, Benjamin A

    2016-01-01

    Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis.

  13. POSSIBILITY OF PHARMACOMODULATION OF THE HYPERSENSITIVE RHINITIS JOINED WITH THE NASAL POLYPOSIS

    Directory of Open Access Journals (Sweden)

    Dejan Ursulović

    2001-11-01

    Full Text Available The research goai is to examine the effects of the local corticosteroidapplication to the number of eosinophils in the nasal secretion of the patients withhypersensitive rhinitis joined with the nasal polyposis. The study comprises 13patients with hypersensitive rhinitis joined with the nasal polyposis; 9 of them madeup the experimental group. The local corticosteroid (bechomethasone dipropionatein water spray was given at 12 hours in individual doses of 200 micrograms to theexperimental group patients in six weeks. During the treatment it was confirmed thatthere was a highly important reduction of the number of eosinophils of the nasalsecretion in the experimental group patients.

  14. Dilemma in the Diagnosis of Povidone-Iodine Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Patil N

    2016-01-01

    Full Text Available Povidone-iodine is a commonly used antiseptic solution in surgical practice. Almost every patient who needs a minor or a major surgical procedure (sometimes, a medical procedure too gets exposed to this antiseptic. Even though the use of this antiseptic is widespread, the number of cases reporting hypersensitivity to it is meagre. This case report highlights a case of povidone-iodine – induced hypersensitivity, which presented a great difficulty in diagnosis, due to the usage of other drugs that could have been more likely causes for this hypersensitivity.

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Anne Derbise

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

  18. Correlations between Ape1/Ref-1, ICAM-1 and IL-17A Levels in Serum and Radiation Pneumonitis for Local Advanced Non-small Cell Lung Cancer Patients

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    Leiming GUO

    2018-05-01

    Full Text Available Background and objective The main manifestations of radiation pneumonitis are injury of alveolar epithelial and endothelial cells, abnormal expression of cytokines, abnormal proliferation of fibroblasts and synthesis of fibrous matrix. The occurrence of radiation pneumonitis is associated with multiplecytokine level abnormality. These cytokines can also be used as bio-markers to predict the occurrence of radiation pneumonitis. This study was to evaluate the correlation between the change of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1, intercellular adhesion molecules 1 (ICAM-1 and interleukin-17A (IL-17A before and after radiotherapy and radiation pneumonitis for local advanced non-small cell lung cancer (NSCLC patients with concurrent chemoradiotherapy. Methods NSCLC patients (68 cases were treated with concurrent radiotherapy and chemotherapy, every patient’s normal tissue were controlled with a same radation dose. 68 local advanced NSCLC patients with concurrent chemoradiotherapy were detected the levels of Ape1/Ref-1, ICAM-1 and IL-17A in serum by ELISA before radiotherapy and in the 14th week after radiotherapy. Acute and advanced radiation pulmonary injury was graded according to Radiation Therapy Oncology Group/European Organization For Research and Treatment (RTOG/EORTC diagnostic and grading criteria. Grade 2 or more radiation pneumonitis was taken as the main end point. Results Eighteen cases out of 68 developed radiation pneumonitis, 50 of 68 cases have no radiation pneumonia development. There was no significant change of Ape1/Ref-1 levels before and after radiotherapy in radiation pneumonitis group (P>0.05. There was no significant change of Ape1/Ref-1 concentration in serum after radiotherapy between radiation pneumonitis group and non-radiation pneumonitis group (P>0.05. Compared with before radiotherapy, upregulation degree of ICAM-1 levels in radiation pneumonitis group was significantly higher than that in

  19. IN VITRO MODELS TO EVALUATE DRUG-INDUCED HYPERSENSITIVITY: POTENTIAL TEST BASED ON ACTIVATION OF DENDRITIC CELLS

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    Valentina Galbiati

    2016-07-01

    Full Text Available Hypersensitivity drug reactions (HDRs are the adverse effect of pharmaceuticals that clinically resemble allergy. HDRs account for approximately 1/6 of drug-induced adverse effects, and include immune-mediated ('allergic' and non immune-mediated ('pseudo allergic' reactions. In recent years, the severe and unpredicted drug adverse events clearly indicate that the immune system can be a critical target of drugs. Enhanced prediction in preclinical safety evaluation is, therefore, crucial. Nowadays, there are no validated in vitro or in vivo methods to screen the sensitizing potential of drugs in the pre-clinical phase. The problem of non-predictability of immunologically-based hypersensitivity reactions is related to the lack of appropriate experimental models rather than to the lack of -understanding of the adverse phenomenon.We recently established experimental conditions and markers to correctly identify drug associated with in vivo hypersensitivity reactions using THP-1 cells and IL-8 production, CD86 and CD54 expression. The proposed in vitro method benefits from a rationalistic approach with the idea that allergenic drugs share with chemical allergens common mechanisms of cell activation. This assay can be easily incorporated into drug development for hazard identification of drugs, which may have the potential to cause in vivo hypersensitivity reactions. The purpose of this review is to assess the state of the art of in vitro models to assess the allergenic potential of drugs based on the activation of dendritic cells.

  20. Progressive anticonvulsant hypersensitivity syndrome associated with change of drug product

    DEFF Research Database (Denmark)

    Sabroe, T.P.; Sabers, A.

    2008-01-01

    This report describes the laboratory and physical manifestations of lamotrigine-like toxicity in a young man with refractory epilepsy receiving lamotrigine presenting as anticonvulsant hypersensitivity syndrome (AHS) associated with an abrupt change of drug product Udgivelsesdato: 2008/6...

  1. The radiation hypersensitivity of cells at mitosis.

    Science.gov (United States)

    Stobbe, C C; Park, S J; Chapman, J D

    2002-12-01

    Mitotic cells are hypersensitive to ionizing radiation, exhibiting single-hit inactivation coefficients near to those of repair deficient cell lines and lymphocytes. To elucidate possible mechanisms for this hypersensitivity, the kinetics of oxygen radiosensitization, the proportion of indirect effect by OH radicals and the kinetics of radiation-induced DNA strand breakage in the chromatin of mitotic cells were investigated. Synchronized populations of >90% mitotic HT-29 cells were obtained by the mitotic shake-off method. Cells were irradiated at indirect effect of OH radicals was investigated with the radical scavenger, DMSO. DNA strand breakage was measured by the comet assay. Mitotic HT-29 cell inactivation is well described by a single-hit inactivation coefficient (alpha) of 1.14 +/- 0.06 Gy(-1). The oxygen enhancement ratio of mitotic cells (at 10% survival) was found to be approximately 2.0, significantly lower than the value of 2.8 measured for interphase (asynchronous) cells. More than 60% of mitotic cell killing was eliminated when the media contained 2 M DMSO, indicating that indirect effect is as important in the killing of mitotic cells as it is for interphase cells. The chromatin in mitotic cells was found to be ~2.8 times more sensitive to radiation-induced DNA single-strand breakage than the chromatin of interphase cells. The alpha-inactivation coefficient of mitotic HT-29 cells was ~30 times larger than that of interphase cells. Mitotic cell chromatin appears to contain intrinsic DNA breaks that are not lethal. In addition, chromatin in mitotic cells was found to be more susceptible to radiation-induced DNA strand-breakage than the dispersed chromatin of interphase cells. How the enhanced production of these simple DNA lesions (that are usually reparable) translates into the lethal (non-reparable) events associated with alpha-inactivation is not known. The compaction/dispersion status of DNA throughout the cell cycle appears to be an important

  2. DEVELOPMENT OF A PEROXIDASE-ANTIPEROXIDASE (PAP) TECHNIQUE FOR THE IDENTIFICATION OF HAEMOPHILUS-SOMNUS IN PNEUMONIC CALF LUNGS IN DENMARK

    DEFF Research Database (Denmark)

    Tegtmeier, Conny; Jensen, N.E.; Jensen, H.E.

    1995-01-01

    A peroxidase-antiperoxidase (PAP) technique was developed for the identification of Haemophilus somnus bacteria in lung tissues of calves. Antisera raised against somatic and wall antigens of a Danish and American strain of H. somnus were produced. Experimentally infected murine tissues were used...... strain of H. somnus revealed the highest sensitivity in the PAP technique and became specific following absorption. Heterologous absorption also rendered this antiserum specific in crossed immunoelectrophoresis. Subsequently, the PAP technique was applied on formalin-fixed pneumonic lung tissues of 86...... calves. An immunodiagnosis of H. somnus pneumonia was obtained in 15 of 17 lungs from which the bacterium had been isolated. Moreover, immunostained bacteria were also demonstrated in 20 lungs from which H. somnus had not been isolated. Thus, application of immunohistochemistry significantly enhanced...

  3. A Rare Diabetic Autonomic Neuropathy: Carotid Sinus Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Ahmet Kaya

    2016-03-01

    Full Text Available Carotid sinus hypersensitivity is a common cause of fainting and falls in the elderly, and can be diagnosed by carotid sinus massage. We present a 67-year-old diabetic man who was admitted with hyperglycemia. During thyroid examination, clouding of consciousness occurred with unilateral palpation. Asystole was documented for 4.8 seconds and suspected for 7 seconds upon carotid sinus massage. A cardioverter defibrillator was implanted. Carotid sinus hypersensitivity should be kept in mind when examining diabetic patients.

  4. Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update

    OpenAIRE

    Sánchez-Borges, Mario; Caballero-Fonseca, Fernan; Capriles-Hulett, Arnaldo; González-Aveledo, Luis

    2010-01-01

    After beta lactam antibiotics, hypersensitivity reactions to nonsteroidal antiinflammatory drugs are the second cause of hypersensitivity to drugs. Acute manifestations affect the respiratory tract (aspirin exacerbated respiratory disease), the skin (urticaria and angioedema), or are generalized (anaphylaxis). Correct diagnosis and treatment in order to prevent unnecessary morbidity and the potential risk of death from these severe reactions, and to provide proper medical advice on future dru...

  5. An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Chun-Bing Chen

    2018-01-01

    Full Text Available Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS/drug-induced hypersensitivity syndrome (DIHS, or Stevens–Johnson syndrome (SJS/toxic epidermal necrolysis (TEN. Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs. The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity.

  6. An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity

    Science.gov (United States)

    Abe, Riichiro; Pan, Ren-You; Wang, Chuang-Wei

    2018-01-01

    Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR) molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity. PMID:29651444

  7. Desensitization for Drug Hypersensitivity to Chemotherapy and Monoclonal Antibodies.

    Science.gov (United States)

    Bonamichi-Santos, Rafael; Castells, Mariana

    2016-01-01

    Chemotherapies drugs and monoclonal antibodies are key components of the treatment of cancer patients and patients with chronic inflammatory conditions to provide increase in life expectancy and quality of life. Their increased use has lead to an increase in drugs hypersensitivity reactions (DHR) worldwide. DHR to those agents prevented their use and promoted the use of second line therapies to protect patients' hypersensitive reactions and anaphylaxis. Second line medications may not fully address the patients' medical condition and it is desirable to keep patients on first line therapy. Drug hypersensitivity symptoms can range from mild cutaneous reactions to life-threatening anaphylaxis. Rapid drug desensitization (RDD) is a novel approach to the management of drug hypersensitivity reactions which are IgE and non-IgE mediated. Through the diferent desensitization protocols patients can receive the full dose of the medications that they have presented a hypersensitive reaction and been protected against anaphylaxis. This review looks at the current literature on hypersensitivity reactions (HSR) to chemotherapy drugs and monoclonal antibodies and the potential use of RDD for their management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Nonimmediate hypersensitivity reactions to iodinated contrast media.

    Science.gov (United States)

    Gómez, Enrique; Ariza, Adriana; Blanca-López, Natalia; Torres, Maria J

    2013-08-01

    To provide a detailed analysis of the latest findings on the mechanisms underlying the nonimmediate reactions to iodinated contrast media and comment on the recent advances in diagnosis, focusing on the roles of the skin test, drug provocation test (DPT), and lymphocyte transformation test (LTT). Several studies have reported new findings supporting an important role for T-lymphocytes in the nonimmediate reactions to iodinated contrast media. The LTT has been used as an in-vitro tool for diagnosis, but with variable results. However, the inclusion of autologous monocyte-derived dendritic cells as professional antigen-presenting cells has improved the sensitivity of this test. Regarding in-vivo diagnosis, although skin testing has been routine, it has now been shown that its sensitivity and negative predictive value are low. Recent studies have demonstrated that the DPT is a well tolerated and useful procedure that is necessary to confirm the diagnosis of nonimmediate hypersensitivity reactions to iodinated contrast media. Nonimmediate reactions to contrast media are usually T-cell mediated. Diagnosis is based on skin testing, although its sensitivity and negative predictive value are not optimal. Consequently, drug provocation testing is often needed to confirm the diagnosis and also to seek alternative contrast media that can be tolerated.

  9. Severe dapsone hypersensitivity syndrome in a child

    Directory of Open Access Journals (Sweden)

    So Yoon Choi

    2013-06-01

    Full Text Available Dapsone (4,4'-diaminodiphenylsulfone, DDS, a potent anti-inflammatory agent, is widely used in the treatment of leprosy and several chronic inflammatory skin diseases. Dapsone therapy rarely results in development of dapsone hypersensitivity syndrome, which is characterized by fever, hepatitis, generalized exfoliative dermatitis, and lymphadenopathy. Here, we describe the case of an 11-year-old Korean boy who initially presented with high fever, a morbilliform skin rash, generalized lymphadenopathy, hepatosplenomegaly, and leukopenia after 6 weeks of dapsone intake. Subsequently, he exhibited cholecystitis, gingivitis, colitis, sepsis, aseptic meningitis, disseminated intravascular coagulation, syndrome of inappropriate antidiuretic hormone secretion, pneumonia, pleural effusions, peritonitis, bronchiectatic changes, exfoliative dermatitis, and acute renal failure. After 2 months of supportive therapy, and prednisolone and antibiotic administration, most of the systemic symptoms resolved, with the exception of exfoliative dermatitis and erythema, which ameliorated over the following 4 months. Agranulocytosis, atypical lymphocytosis, aseptic meningitis, and bronchiectatic changes along with prolonged systemic symptoms with exfoliative dermatitis were the most peculiar features of the present case.

  10. Gelofen Induced Hypersensitivity: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    M. Nikkhah Rankohie

    2016-07-01

    Full Text Available Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs are drugs commonly pre-scribed in dental practice for the management of pain and swelling. But, rarely hypersensitiv-ity reactions are reported. Case Report: A 28 year old woman underwent periodontal plastic surgery (gingival graft. Postoperative analgesics (400 mg Gelofen ,oral and antibiotics were administrated for the patient. Three hours after discharge of patient, she complained of redness, itching , rapid swelling of her eyes in 10 minutes, and watery eye discharge 1 hour after taking the drugs. She was treated with 8mg/2ml mg Dexamethasone IM at the dental department and with Hy-drocortisone 100mg/ml IM and antihistamine drugs at the hospital. Conclusion: There are no published protocols and sensitivity and specifity of skin pick testing and patch testing for Gelofen. So avoidance of re-exposure is the best management strategy. The use of Cox-2 specific medications would be a proper alternative for pain relief. (Sci J Hamadan Univ Med Sci 2016; 23 (2:179-183

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-05-15

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

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

    Science.gov (United States)

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

    2016-02-19

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

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

    International Nuclear Information System (INIS)

    Castillo, Richard; Guerrero, Thomas; Pham, Ngoc; Ansari, Sobiya; Meshkov, Dmitriy; Castillo, Sarah; Li, Min; Olanrewaju, Adenike; Hobbs, Brian; Castillo, Edward

    2014-01-01

    A retrospective analysis is performed to determine if pre-treatment [ 18 F]-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) image derived parameters can predict radiation pneumonitis (RP) clinical symptoms in lung cancer patients. We retrospectively studied 100 non-small cell lung cancer (NSCLC) patients who underwent FDG PET/CT imaging before initiation of radiotherapy (RT). Pneumonitis symptoms were evaluated using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4) from the consensus of 5 clinicians. Using the cumulative distribution of pre-treatment standard uptake values (SUV) within the lungs, the 80th to 95th percentile SUV values (SUV 80 to SUV 95 ) were determined. The effect of pre-RT FDG uptake, dose, patient and treatment characteristics on pulmonary toxicity was studied using multiple logistic regression. The study subjects were treated with 3D conformal RT (n = 23), intensity modulated RT (n = 64), and proton therapy (n = 13). Multiple logistic regression analysis demonstrated that elevated pre-RT lung FDG uptake on staging FDG PET was related to development of RP symptoms after RT. A patient of average age and V 30 with SUV 95 = 1.5 was an estimated 6.9 times more likely to develop grade ≥ 2 radiation pneumonitis when compared to a patient with SUV 95 = 0.5 of the same age and identical V 30 . Receiver operating characteristic curve analysis showed the area under the curve was 0.78 (95% CI = 0.69 – 0.87). The CT imaging and dosimetry parameters were found to be poor predictors of RP symptoms. The pretreatment pulmonary FDG uptake, as quantified by the SUV 95 , predicted symptoms of RP in this study. Elevation in this pre-treatment biomarker identifies a patient group at high risk for post-treatment symptomatic RP

  14. CT findings of pulmonary consolidation: focused on tuberculosis, malignant obstructive pneumonitis, and lung abscess

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Wang Jung; Kim, Sung Jin; Cha, Sang Hoon; Park, Kit Sun; Kim, Dae Young [College of Medicine, Chung Buk National University, Cheongju (Korea, Republic of); Han, Gi Seuk [Seoul National University Hospital, Seoul (Korea, Republic of)

    1994-12-15

    The aim of our study was to identify the CT features helpful in the differential diagnosis of Iobar consolidation. We evaluated the CT findings in 52 consecutive patients with lobar consolidation which were proved to be pulmonary tuberculosis(n=24), malignant obstructive pneumonitis due to bronchogenic carcinoma(n=21), and lung abscess(n=7). We retrospectively reviewed CT scans with respect to 1) number of cavities or low attenuation area suggesting necrosis(we described these as cavity), 2) the contour of cavity, 3) enhancement of the cavity wall, 4) enhancement of pleura, 5) small nodules adjacent to the consolidation, 6) similar lesion in other location in lung, 7) air-bronchogram 8) mediastinal lymph node enlargement, and 9) extrapleural change. The helpful CT findings in the patients with pulmonary tuberculosis were multiple cavities(more than three; 79.2%), small nodules adjacent to the lobar consolidation(75.0%), similar lesion in another lobe or lung(91.7%), air-bronchogram(91.7%), and mediastinal lymph node enlargement(58.3%). Although extrapleural change had low sensitivity it was highly specific for pulmonary tuberculosis(sensitivity, 43.5%; specificity, 91.7%). Multiple cavities(61.9%) and mediastinal lymph node enlargement(52.4%) were common findings of malignant obstructive pneumonitis. In the patients with lung abscess, the common findings were small number of cavities(one or two, 85.7%) and air-bronchogram(85.7%). However, other findings of pulmonary tuberculosis were rarely seen in the patients with malignant obstructive pneumonitis or lung abscess. The CT findings of lobar consolidation may be used as useful adjuncts in the differential diagnosis of lobar consolidation.

  15. CT findings of pulmonary consolidation: focused on tuberculosis, malignant obstructive pneumonitis, and lung abscess

    International Nuclear Information System (INIS)

    Kim, Wang Jung; Kim, Sung Jin; Cha, Sang Hoon; Park, Kit Sun; Kim, Dae Young; Han, Gi Seuk

    1994-01-01

    The aim of our study was to identify the CT features helpful in the differential diagnosis of Iobar consolidation. We evaluated the CT findings in 52 consecutive patients with lobar consolidation which were proved to be pulmonary tuberculosis(n=24), malignant obstructive pneumonitis due to bronchogenic carcinoma(n=21), and lung abscess(n=7). We retrospectively reviewed CT scans with respect to 1) number of cavities or low attenuation area suggesting necrosis(we described these as cavity), 2) the contour of cavity, 3) enhancement of the cavity wall, 4) enhancement of pleura, 5) small nodules adjacent to the consolidation, 6) similar lesion in other location in lung, 7) air-bronchogram 8) mediastinal lymph node enlargement, and 9) extrapleural change. The helpful CT findings in the patients with pulmonary tuberculosis were multiple cavities(more than three; 79.2%), small nodules adjacent to the lobar consolidation(75.0%), similar lesion in another lobe or lung(91.7%), air-bronchogram(91.7%), and mediastinal lymph node enlargement(58.3%). Although extrapleural change had low sensitivity it was highly specific for pulmonary tuberculosis(sensitivity, 43.5%; specificity, 91.7%). Multiple cavities(61.9%) and mediastinal lymph node enlargement(52.4%) were common findings of malignant obstructive pneumonitis. In the patients with lung abscess, the common findings were small number of cavities(one or two, 85.7%) and air-bronchogram(85.7%). However, other findings of pulmonary tuberculosis were rarely seen in the patients with malignant obstructive pneumonitis or lung abscess. The CT findings of lobar consolidation may be used as useful adjuncts in the differential diagnosis of lobar consolidation

  16. Central lung tumors with obstructive pneumonitis; ultrasonographic findings and usefulness of ultrasound-guided biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong An; Kim, Sun Su; Seon, Young Seok; Lee, Kyoung Rok; Kim, Byoung Geun; Park, Byung Ran; Kim, Se Jong [Kwangju Christian Hospital, Kwangju (Korea, Republic of)

    2001-02-01

    To determine the ultrasonographic findings and assess the usefulness of ultrasound (US)-guided biopsy of central lung tumors in patients with obstructive pneumonitis. Fourteen patients with central lung tumors causing obstructive pneumonitis, as seen on chest radiographs and chest CT scans, were examined between January 1997 and January 2000. In no patient conclusive histologic diagnosis obtained by means of bronchoscopic biopsy or sputum cytology. Eleven patients were men and three were women, and their ages ranged from 45 to 83 (mean, 64) years. For all examinations, real-time, linear-array, convex US units with a 3.75-and a 5.0-MHz transducer were used. The images obtained were analyzed for evidence of consolidation or atelectasis in the lung, demonstrable tumors, and tumor size and echogenicity. For US-guided percutaneous transthoracic biopsy, 19.5G automatic biopsy devices, were employed. Lung consolidation due to a wedge-shaped, homogeneous, hypoechoic lesion was revealed by sonographic fluid bronchograms, air bronchograms, air alvelograms, and visualization of intraparenchymal pulmonary vessels, which showed appropriate motion with respiration. The tumor presumed to be causing obstruction was seen as a hypoechoic nodule near the hilum or as a well-defined hyperechoic mass inside the partially consolidated lung. Pleural effusion was observed in one case. The cytologic findings indicated the presence of squamous cell carcinoma (n=4), adenocarcinoma (n=4), small cell carcinoma (n=3), non-small cell carcinoma (n=2) and large cell carcinoma (n=1). The success rate was 100%, and there were no complications. In patients with central lung tumors causing obstructive pneumonitis, chest ultrasonography and US-guided biopsy are useful adjunctive diagnostic modalities and techniques.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-11-15

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

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

    Science.gov (United States)

    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. © 2015 The Authors. European Journal of Neuroscience published by Federation of

  19. Hypersensitivity myocarditis associated with ephedra use.

    Science.gov (United States)

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

    1999-01-01

    Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.

  20. Hypersensitivity to thrombin of platelets from hypercholesterolemic rats

    International Nuclear Information System (INIS)

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

    1986-01-01

    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 14 C-serotonin. In the presence of acetylsalicyclic acid (ASA) (to inhibit thromboxane A 2 (TXA 2 ) formation) and creatine phosphate/creatine phosphokinase (CP/CPK) (to remove released ADP), HC platelets aggregated more (26 +/- 1%) and released more 14 C (9.1 +/- 2.0%) than NC platelets (aggregation: 0%, p 14 C release: 1.5 +/- 0.5%, p 2 formation is involved in the hypersensitivity of HC platelets to thrombin. Total binding of 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 2 formation, the action of released ADP or increased thrombin binding

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

    Science.gov (United States)

    Riehm, Julia M; Löscher, Thomas

    2015-07-01

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

  2. Prevention of radiation pneumonitis from inhaled 144Ce by lung lavage in beagle dogs

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Mauderly, J.L.; Boecker, B.B.; Hahn, F.F.; McClellan, R.O.

    1975-01-01

    This study was performed to evaluate bronchopulmonary lavage and chelation therapy as a treatment method to prevent the development of radiation pneumonitis after inhalation of a radioactive aerosol. Twelve beagle dogs were exposed to an aerosol of cerium-144 in fused clay particles resulting in initial lung burdens from 47 to 64 μCi of 144 Ce per kg of body weight. Eight of the dogs were treated with a series of 10 bronchopulmonary lavages and 10 intravenous injections of calcium diethylenetriamine pentaacetate acid during the first 56 days after exposure to remove the deposited 144 Ce; the remaining 4 exposed dogs received no treatment. An additional 4 dogs were exposed to stable cerium and were given the course of treatment as an additional control group. Three of the 4 untreated dogs and 2 of the 8 treated dogs died 171 to 246 days after exposure with radiation pneumonitis or pulmonary fibrosis, or both. All but one of the remaining dogs were alive and apparently in good clinical health 550 days after exposure; the one dog had radiographic indications of pulmonary fibrosis by 365 days after exposure. The relative distribution of 144 Ce in the lungs and other major organs was similar in the treated and untreated dogs that died

  3. Lipid peroxidation in radiation pneumonitis in mouse lung and its preventation

    International Nuclear Information System (INIS)

    Kodama, Akihisa; Tsujino, Kayoko; Kono, Michio

    1998-01-01

    Lipid peroxidation of the lung in irradiated C57BL6J mice was analyzed by gas chromatography. Among six major fatty acids in the mouse lung tissue, the amounts of two unsaturated fatty acids, arachidonic acid and DHA reduced one day after irradiation, and then recovered up to the level of in the control group four weeks after irradiation. In contrast, the amounts of stearic and palmitic acid did not change significantly. The mice fed with vitamin E-enriched food showed no significant changes of fatty acids which were compatible with pathophysiological findings 4 weeks after irradiation. Reduction of both arachidonic acid and DHA following lipid peroxidation in lung tissue, was assumed to play an important role in development of radiation pneumonitis. Vitamin E seems to enable to prevent or reduce the occurrence and progression of radiation pneumonitis, but as a radical scavenger, it may also weaken the anti-tumor growth effect of low linear energy transfer (LET) irradiation as photon. (author)

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

    Directory of Open Access Journals (Sweden)

    He Liu

    2015-04-01

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

  5. Asthma and chemical hypersensitivity: prevalence, etiology, and age of onset.

    Science.gov (United States)

    Caress, S M; Steinemann, A C

    2009-02-01

    This study investigates asthma's national prevalence and potential overlap with chemical hypersensitivity. It also examines asthma's etiology, age of onset, and demographic characteristics. Data were collected from a geographically weighted random sample of the continental U.S. (1058 cases), in four seasonal cohorts (2005-2006). The study found that 12.9% of the sample report asthma, 11.6% report chemical hypersensitivity, and 31.4% of those with asthma report chemical hypersensitivity. Among asthmatics, 38% report irritation from scented products, 37.2% report health problems from air fresheners, and 13.6% report their asthma was caused by toxic exposure. Asthma cases affected each racial/ethic group in roughly the same proportion, with nearly 50% classified as childhood onset.

  6. Multinational experience with hypersensitivity drug reactions in Latin America.

    Science.gov (United States)

    Jares, Edgardo José; Sánchez-Borges, Mario; Cardona-Villa, Ricardo; Ensina, Luis Felipe; Arias-Cruz, Alfredo; Gómez, Maximiliano; Barayazarra, Susana; Bernstein, Jonathan A; Serrano, Carlos D; Cuello, Mabel Noemi; Morfin-Maciel, Blanca María; De Falco, Alicia; Cherrez-Ojeda, Iván

    2014-09-01

    Epidemiologic drug allergy data from Latin America are scarce, and there are no studies on specific procedures focusing on this topic in Latin America. To assess the clinical characteristics and management of hypersensitivity drug reactions in different Latin American countries. An European Network of Drug Allergy questionnaire survey was implemented in 22 allergy units in 11 Latin American countries to report on consecutive patients who presented with a suspected hypersensitivity drug reaction. Each unit used its own protocols to investigate patients. Included were 868 hypersensitivity drug reactions in 862 patients (71% of adults and elderly patients were women and 51% of children were girls, P = .0001). Children presented with less severe reactions than adults and elderly patients (P Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. FOOD HYPERSENSITIVITY AND PRODUCTS OF ANIMAL ORIGIN RESOURCES

    Directory of Open Access Journals (Sweden)

    A. B. Lisitsyn

    2017-01-01

    Full Text Available The number of people with food hypersensitivity, namely food intolerance and food allergies, grows every year. Food intolerance is classified into following types: enzymopathy; leaky gut syndrome; psychogenic food intolerance; detoxification insufficiency and true food intolerance. Food allergens mainly are glycoproteins, haptensor polypeptides. Most cases of food allergy are IgE-mediated allergic reactions. Recent discoveries in medicine, detailing and classification of food hypersensitivity require further researches to develop modern techniques and product recipes with specified propertiesfor consumers with food hypersensitivity. Existing technologies are based on the elimination and or reduction of the content of the allergenic substance in food. The article provides an overview of causes of food intolerance and food allergy, legislative background, a list of food allergens and methods of control, market profile of hypoallergenic produce and scientific approaches to creating hypoallergenic food products based on raw materials of animal origin.

  8. [Adaptive desensitization for acetylsalicylic acid hypersensitivity: A success story?].

    Science.gov (United States)

    Mühlmeier, G; Hausch, R; Maier, H

    2015-10-01

    Adaptive desensitization still remains the only causative therapy for acetylsalicylic acid (ASA) hypersensitivity and is carried out nearly worldwide. To date there are hardly any data available on disease development under current desensitization therapy and longitudinal data in particular are missing. Out of a large collective of patients with proven hypersensitivity to ASA, 194 patients with initiated desensitization treatment were observed for periods up to 5 years (average 32 months). Patients with immediate reactions to systemic challenge tests revealed a response rate of 77% after 12 months of therapy. In this period 12% reached complete remission, 38% showed a clear reduction in symptoms, 32% reached partial remission, 13% remained unchanged and 5% suffered from disease progression. Adaptive desensitization therapy for hypersensitivity to ASA has been shown to be an effective causative therapy and chronic hyperplastic sinusitis as well as bronchial asthma could be improved. For the determination of maintenance dosages and required time periods more data are needed.

  9. Metal hypersensitivity after knee arthroplasty: fact or fiction?

    Science.gov (United States)

    Innocenti, Massimo; Vieri, Berti; Melani, Tommaso; Paoli, Tommaso; Carulli, Christian

    2017-06-07

    Hypersensitivity to metals in the general population has an incidence of about 15%, and in rising also for the higher number of joint replacements in the last decades. Total Knee Arthroplasty (TKA) represents the most performed orthopaedic procedure during last years, and it seems to be particularly associated with sensitization after surgery. On the other hand, there is a rising amount of patients with painful but well implanted and functioning TKAs: in certain cases, after the exclusion of the most frequent causes of failure, a condition of hypersensitivity may be found, and a revision with anallergic implants is mandatory. The present study is a review of the potential problems related to hypersensitivity in TKA, its possible diagnostic procedures, and the surgical options to date available. Medical history, patch testing, and other specific laboratory assays are useful to assess a status of metals hypersensitivity before surgery in subjects undergoing a knee replacement, or even after TKA in patients complaining pain in otherwise well implanted and aligned prostheses. However, few groups worlwide deal with such condition, and all proposed diagnostic protocols may be considered still today conjectural. On the other hand, these represent the most updated knowledge of this condition, and may be useful for both the patient and the orthopaedic surgeon. Once assessed a possible or ascertained allergy to metals, several options are available for primary andr revision knee surgery, in order to avoid the risk of hypersensitivity. A review of the recent publications on this topic and an overview of the related aspects has been made to understand a condition to date considered negligible. Hypersensitivity to metals has not to be nowadays considered a "fiction", but rather a possible preoperative risk or a postoperative cause of failure of TKA. Crucial is the information of patients and the medical history, associated in suspect cases to laboratory testings. Today in the

  10. Efficacy of two commercially available dentifrices in reducing dentinal hypersensitivity

    Directory of Open Access Journals (Sweden)

    Prasad KVV

    2010-01-01

    Full Text Available Objective: A parallel design clinical study evaluated reduction in hypersensitivity after brushing for 12 weeks with Anchor toothpaste (containing potassium citrate, zinc citrate, triclosan and sodium monofluorophosphate (test and Colgate Total (sodium fluoride, silica, triclosan and copolymer (control dentifrices. Materials and Methods: Sixty adults with sensitivity to hot and cold stimulus in at least two tooth surfaces were stratified at the baseline examination by tactile, hot and cold stimuli scores in two balanced groups. Subjects were randomly allocated the test and control dentifrices and evaluated after 6 and 12 weeks of dentifrice use for hypersensitivity. Results: The two teeth that were selected in each patient were designated as two different sets. The 12 th -week scores as compared to baseline scores for tactile, heat and cold tests in the test group showed a reduction in tooth hypersensitivity by 36.67% (P < 0.01, 20.35% (P < 0.01 and 53.64 % (P < 0.01, respectively, in the first set of teeth and 43.75% (P < 0.01, 24.48% (P < 0.01 and 59.78% (P < 0.01, respectively, in the second set of teeth. The 12 th -week scores as compared to baseline scores for tactile, heat and cold tests in the control group showed a reduction in tooth hypersensitivity by 42.86% (P < 0.01, 13.02% (P < 0.01 and 45.14% (P < 0.01, respectively, in the first set of teeth and 40% (P < 0.01, 16.59% (P < 0.01 and 44.16% (P < 0.01, respectively, in the second set of teeth. Conclusions: Both the products reduced dentinal hypersensitivity in the study subjects at the end of the 12-week period. However, there was no statistically significant difference in reduction in hypersensitivity between the two products.

  11. Corticosteroid hypersensitivity studies in a skin allergy clinic.

    Science.gov (United States)

    Berbegal, L; DeLeon, F J; Silvestre, J F

    2015-12-01

    Corticosteroids can cause hypersensitivity reactions, particularly delayed-type allergic reactions. A new classification system for testing hypersensitivity to corticosteroids distributes the drugs into 3 groups according to molecular structure; patients are classified according to whether they are allergic to agents in 1 or more of the groups. We aimed to describe the clinical characteristics of corticosteroid-allergic patients treated at our clinic and apply the new classification system to them; we also compared these patients' characteristics to those of others treated at our clinic. Retrospective study of cases of delayed-type corticosteroid hypersensitivity treated in the skin allergy clinic of a tertiary level hospital over an 11-year period. We reviewed the records of 2857 patients, finding 33 with at least one positive patch test result showing corticosteroid hypersensitivity. Atopic dermatitis and hand involvement were less common in our corticosteroid-allergic patients. All were allergic to a group 1 corticosteroid (most often, budesonide, the culprit in 87.9%). Testing with a specific corticosteroid series revealed that 14 (42.4%) were also allergic to corticosteroids in group 2 and/or group 3. None were allergic exclusively to group 2 or group 3 agents. Twenty-one patients were exposed to a corticosteroid cream from a group their patch test results indicated allergy to; 13 of them (61.9%) did not develop a hypersensitivity reaction. The Spanish standard series only contains group 1 corticosteroids. In the interest of improving allergy management, we recommend testing with a specific corticosteroid series and a patient's own creams whenever patch testing with a standard series reveals a hypersensitivity reaction to corticosteroids. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  12. Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs)

    DEFF Research Database (Denmark)

    Nissen, Christoffer V; Bindslev-Jensen, Carsten; Mørtz, Charlotte G

    2015-01-01

    BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are reported to be the second most common cause of drug hypersensitivity. In 2011, experts from the EAACI/ENDA group and GA(2)LEN proposed a new classification system for NSAID hypersensitivity. The aim of this study was to classify...... responders reacted to non-pyrazolone drugs. Only one patient could not be classified according to the EAACI/ENDA system. An overlap between respiratory and cutaneous symptoms was found in 15/39 (38%) of patients. CONCLUSIONS: All but one of our patients could be classified according to the EAACI...

  13. Cutaneous and systemic hypersensitivity reactions to metallic implants

    DEFF Research Database (Denmark)

    Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C

    2011-01-01

    Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous....... However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis...

  14. Functional dyspepsia: The role of visceral hypersensitivity in its pathogenesis

    Institute of Scientific and Technical Information of China (English)

    John Keohane; Eamonn M M Quigley

    2006-01-01

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

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

    LENUS (Irish Health Repository)

    Keohane, John

    2012-02-03

    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.

  16. Association of HLA genotypes with phenobarbital hypersensitivity in children.

    Science.gov (United States)

    Manuyakorn, Wiparat; Mahasirimongkol, Surakameth; Likkasittipan, Plernpit; Kamchaisatian, Wasu; Wattanapokayakit, Sukanya; Inunchot, Wimala; Visudtibhan, Anannit; Wichukchinda, Nuanjun; Benjaponpitak, Suwat

    2016-10-01

    Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes (MPs) to severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drug hypersensitivity has been demonstrated to be associated with variations in the HLA genotypes. This study was to investigate the association between the variations of HLA genotypes and phenobarbital hypersensitivity in Thai children. The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included SCARs and MPs. The control patients were Thai children of a corresponding age who had taken phenobarbital for at least 12 weeks without any hypersensitivity reaction. Blood samples were collected for HLA genotyping by using a reverse-sequence-specific oligonucleotide (SSO) probes method. The carrier rates of HLA alleles were compared between 47 cases (27 SCARs and 20 MPs) and 54 controls. The carrier rates of HLA-A*01:01 and HLA-B*13:01 were significantly higher in the phenobarbital-induced SCARs than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [OR] 11.66, 95% confidence interval [CI] 1.21-578.19; 37.04% vs. 11.11%, p = 0.009, OR 4.60, 95%CI 1.29-17.98). There was a trend of a higher carrier rate of HLA-C*06:02 in the phenobarbital-induced SCARs when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, OR 3.31, 95% CI 0.88-13.31). In contrast to the phenobarbital-induced SCARs, only the HLA-A*01:01 carrier rate in the phenobarbital-induced MPs was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, OR 12.69, 95% CI 1.15-661.62). An association between phenobarbital hypersensitivity and HLA-A*01:01 and HLA-B*13:01 has been demonstrated in Thai children

  17. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    Kaman, W.E.; Hawkey, S.; Kleij, D. van der; Broekhuijsen, M.P.; Silman, N.J.; Bikker, F.J.

    2011-01-01

    We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all

  18. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    W.E. Kaman (Wendy); S. Hawkey; D. van der Kleij (Desiree); M.P. Broekhuijsen; N.J. Silman; F.J. Bikker (Floris)

    2011-01-01

    textabstractWe determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The

  19. Chemical pneumonitis

    Science.gov (United States)

    ... cleaning materials such as chlorine bleach, during industrial accidents, or near swimming pools) Grain and fertilizer dust ... and the A.D.A.M. Editorial team. Chemical Emergencies ... about A.D.A.M.'s editorial policy , editorial process and privacy policy . A.D.A.M. is ...

  20. Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

    NARCIS (Netherlands)

    Schurink, A.; Wolc, A.; Ducro, B.J.; Frankena, K.; Garrick, D.J.; Dekkers, J.C.M.; Arendonk, van J.A.M.

    2012-01-01

    Background: Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite

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

    International Nuclear Information System (INIS)

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

    2011-01-01

    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, 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. 18 F-FDG-PET may be useful in the prediction, diagnosis and therapeutic monitoring of radiation pneumonitis.

  2. The Cynomolgus Macaque Natural History Model of Pneumonic Tularemia for Predicting Clinical Efficacy Under the Animal Rule

    Science.gov (United States)

    Guina, Tina; Lanning, Lynda L.; Omland, Kristian S.; Williams, Mark S.; Wolfraim, Larry A.; Heyse, Stephen P.; Houchens, Christopher R.; Sanz, Patrick; Hewitt, Judith A.

    2018-01-01

    Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a Tier 1 select agent. The natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCM) in human populations. Development and licensure of tularemia therapeutics and vaccines need to occur under the Food and Drug Administration's (FDA's) Animal Rule under which efficacy studies are conducted in well-characterized animal models that reflect the pathophysiology of human disease. The Tularemia Animal Model Qualification (AMQ) Working Group is seeking qualification of the cynomolgus macaque (Macaca fascicularis) model of pneumonic tularemia under Drug Development Tools Qualification Programs with the FDA based upon the results of studies described in this manuscript. Analysis of data on survival, average time to death, average time to fever onset, average interval between fever and death, and bacteremia; together with summaries of clinical signs, necropsy findings, and histopathology from the animals exposed to aerosolized F. tularensis Schu S4 in five natural history studies and one antibiotic efficacy study form the basis for the proposed cynomolgus macaque model. Results support the conclusion that signs of pneumonic tularemia in cynomolgus macaques exposed to 300–3,000 colony forming units (cfu) aerosolized F. tularensis Schu S4, under the conditions described herein, and human pneumonic tularemia cases are highly similar. Animal age, weight, and sex of animals challenged with 300–3,000 cfu Schu S4 did not impact fever onset in studies described herein. This study summarizes critical parameters and endpoints of a well-characterized cynomolgus macaque model of pneumonic tularemia and demonstrates this model is appropriate for qualification, and for testing efficacy of tularemia therapeutics under Animal Rule. PMID

  3. Acute radiation dermatitis and pneumonitis in Japanese breast cancer patients with whole breast hypofractionated radiotherapy compared to conventional radiotherapy

    International Nuclear Information System (INIS)

    Osako, Tomo; Oguchi, Masahiko; Kumada, Madoka; Nemoto, Keiko; Iwase, Takuji; Yamashita, Takashi

    2008-01-01

    The objective of this study was to evaluate acute morbidity, radiation dermatitis and pneumonitis, of Japanese patients treated with whole breast hypofractionated radiotherapy (RT) after breast-conserving surgery (BCS), compared to conventional RT. Japanese patients who received whole breast RT after BCS between October 2003 and September 2006 were retrospectively reviewed. Patients who had selected the conventional or hypofractionated schedule received whole breast irradiation of 50 Gy in 25 fractions plus boost or 40 Gy in 16 fractions plus boost. Radiation dermatitis and symptomatic pneumonitis were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Of 443 consecutive patients, 377 (85%) received the conventional schedule and 66 (15%) received the hypofractionated schedule. Of patients treated with the conventional schedule, Grade 0, 1, 2 and 3 radiation dermatitis were observed in 16 (4%), 278 (74%), 77 (20%) and 6 (2%), respectively. Of patients treated with the hypofractionated schedule, Grade 0, 1, 2 and 3 dermatitis were observed in 11 (17%), 49 (74%), 5 (8%) and 1 (1%), respectively. Grade 2-3 dermatitis by the hypofractionated schedule (9%) was observed less frequently than that by the conventional schedule (22%) (chi-square test; P=0.016). Moreover, of patients treated with the conventional schedule, 4 (1%) had Grade 2 radiation pneumonitis. No patient treated with the hypofractionated schedule had symptomatic pneumonitis. Radiation dermatitis and pneumonitis in Japanese patients treated with the hypofractionated schedule is acceptable. Especially, radiation dermatitis by the hypofractionated schedule is milder than that by the conventional schedule. (author)

  4. Agrobacterium -induced hypersensitive necrotic reaction in plant cells

    African Journals Online (AJOL)

    High necrosis and poor survival rate of target plant tissues are some of the major factors that affect the efficiency of Agrobacterium-mediated T-DNA transfer into plant cells. These factors may be the result of, or linked to, hypersensitive defense reaction in plants to Agrobacterium infection, which may involve the recognition ...

  5. Incidence of abacavir hypersensitivity reactions in euroSIDA

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Friis-Møller, Nina; Mocroft, Amanda

    2008-01-01

    BACKGROUND: The aim of the study was to investigate the incidence of abacavir-related hypersensitivity reaction (HSR) and associated deaths in EuroSIDA HIV-1-infected patients. METHODS: Poisson regression models were developed to compare incidence of abacavir discontinuation according to the line...

  6. Auditory Hypersensitivity in Children with Autism Spectrum Disorders

    Science.gov (United States)

    Lucker, Jay R.

    2013-01-01

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

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

    NARCIS (Netherlands)

    Rijt, van der R.; Boom, van den R.; Jongema, Y.; Sloet van Oldruitenborgh-Oosterbaan, M.M.

    2008-01-01

    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

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

    Science.gov (United States)

    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.

  9. Cyproterone acetate in the treatment of oestrogen hypersensitivity vulvovaginitis.

    Science.gov (United States)

    Nguyen, Yvonne; Bradford, Jennifer; Fischer, Gayle

    2018-02-01

    Oestrogen hypersensitivity vulvovaginitis is a rare chronic cyclical vulvovaginitis responsive to oestrogen suppression or antagonism. We present a case series of 16 patients with refractory cyclical vulvovaginitis, all of whom responded to oestrogen suppression with cyproterone acetate. © 2017 The Australasian College of Dermatologists.

  10. Effects of tobacco-smoke on radiation-induced pneumonitis in rats

    International Nuclear Information System (INIS)

    Nilsson, K.; Henriksson, R.; Cai, Y.-Q.; Hellstroem, S.; Bjermer, L.; Hoernqvist Bylunds, S.

    1992-01-01

    To investigate the effect of exposure to tobacco smoke (TS) on the development of irradiation-induced pneumonitis in rats, five groups of animals were investigated including controls (C), tobacco smoke exposed (S), irradiated (RNS) and irradiated and tobacco smoke exposed (RS). An additional group (RS/NS) was exposed to tobacco before irradiation but not afterwards. Results indicate that smoking suppresses the radiation-induced inflammation but to a lesser degree affects the radiation-induced increase in membrane permeability as reflected by increased protein levels in BAL. Moreover, the marked effects on the numbers of mast cells and neutrophils in the RS group may indicate that these cells play an important role in the mechanism by which tobacco smoke modulates the effects of irradiation. When exposure to tobacco smoke was terminated immediately after irradiation (RS/NS), the inflammatory response was unaffected. (author)

  11. An intractable empyema proceeded from radiation pneumonitis after operation of lung cancer

    International Nuclear Information System (INIS)

    Masuya, Daiki; Gotoh, Masashi; Nakashima, Takashi; Okamoto, Taku; Liu, Dage; Ishikawa, Shinya; Yamamoto, Yasumichi; Huang, Cheng-Long; Yokomise, Hiroyasu

    2005-01-01

    A 54-year-old man underwent left upper lobectomy with c-stage IIIA lung squamous cell carcinoma after concurrent chemo-radiotherapy. Radiation pneumonitis focusing on the residual left S 6 appeared after operation. Following steroid pulse treatment, the pneumonitic focus was cavitated and proceeded to pulmonary abscess. Although chest drainage was performed, control of the pulmonary fistula was poor, so an operation was performed. Pulmonary decortication and pleurodesis were performed, but failed to control the fistula and infection. Finally, thoracoplasty, omentoplasty and free rectus abdominis musculocutaneous flap were filled in intrathorasic to manage the fistula. In this case of operation following concurrent chemo-radiotherapy, the original recovery power declined. We therefore conclude this was an intractable case of empyema. (author)

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

    Science.gov (United States)

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

    1984-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Yaron Vagima

    2015-05-01

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

  14. A case of radiation pneumonitis with eosinophilia in bronchoalveolar lavage fluid

    International Nuclear Information System (INIS)

    Kawai, Seiko; Baba, Kenji; Tanaka, Hiroyuki; Takahashi, Daisuke; Yagi, Takeo; Hattori, Tsutomu; Yamaguchi, Etsuro

    2008-01-01

    A 78-year-old man was admitted to our hospital for irradiation therapy of non-resectable primary lung squamous cell carcinoma of the right middle lobe (T3N2M0). The Linac irradiation through opposing 2 gates (2 Gy per day and 60 Gy in total) was performed to the affected area including the metastatic right hilar and mediastinal lymphadenopathy. One week after completing the irradiation therapy, fever developed with infiltrates in the area from the right middle lobe to the right lower lobe, which did not necessarily coincide with the irradiated area Antibiotic therapies were not effective. Both the serum lactic dehydrogenase (LDH) level and eosinophil count in the peripheral blood increased. Bronchoalveolar lavage was performed at the right B 8 , and differential cell counts of the lavage fluid were macrophages, 17%; lymphocytes, 60%; neutrophils, 5%; and eosinophils, 18%. No significant organisms were obtained by culture of the lavage fluid. The %VC and D LCO /VA became lower than before the irradiation therapy. Thus, the patient was given a diagnosis of radiation pneumonitis. Treatment with 40 mg/day oral prednisolone was commenced with a stepwise dose-reduction (5 mg every two weeks) until reaching the maintenance dose of 15 mg/day. The serum LDH level and blood eosinophil count recovered promptly to the normal range. The pulmonary infiltrates and the lung functions substantially improved. There have been few reports of radiation pneumonitis in which eosinophil counts increased in peripheral blood and bronchoalveolar lavage fluid after irradiation therapy. In the present case report, the possible mechanisms for the irradiation-induced eosinophilia were also reviewed. (author)

  15. Hypersensitivity Responses in the Central Nervous System

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen

    2015-01-01

    of pathology in neuromyelitis optica (NMO), a central nervous system (CNS) demyelinating disease where activated neutrophils infiltrate, unlike in MS. The most widely used model for MS, experimental autoimmune encephalomyelitis, is an autoantigen-immunized disease that can be transferred to naive animals...

  16. Early Graphical Appearance of Radiation Pneumonitis Correlates With the Severity of Radiation Pneumonitis After Stereotactic Body Radiotherapy (SBRT) in Patients With Lung Tumors

    International Nuclear Information System (INIS)

    Takeda, Atsuya; Ohashi, Toshio; Kunieda, Etsuo

    2010-01-01

    Purpose: To investigate factors associated with Grade ≥3 radiation pneumonitis (RP) in patients with lung tumors treated with stereotactic body radiotherapy (SBRT). Methods and Materials: We retrospectively analyzed 128 patients with 133 lung tumors treated with SBRT. RP was graded according to the Common Terminology Criteria for Adverse Events version 3.0. Univariate analyses were used to identify predictive factors for RP. Results: The median follow-up period after SBRT was 12 months (range, 5-45 months). Incidences of Grades 0, 1, 2, and 3 RP were 27%, 52%, 16%, and 5%, respectively. No patients suffered Grade 4 or 5 RP. For all patients with Grade 2 or 3, symptoms occurred either simultaneously with or subsequent to graphical appearances. The latent period was the only significant factor associated with Grade ≥3 RP (p < 0.01). A latent period of 1 or 2 months indicated a 40% (6/15) risk for Grade 3. However, the risk for Grade 3 was 1.2% (1/82) 3 months after SBRT. No pretreatment clinical or dosimetric factors were significantly associated with Grade ≥3 RP. However, 4 of 7 patients with Grade 3 RP had severe pulmonary comorbidities. Conclusion: Only the latency period was a significant factor in the development of RP. No pretreatment clinical or dosimetric factors were significantly associated with Grade ≥3 RP. Patients, especially those with severe pulmonary comorbidities, should be carefully observed for the graphical appearance of RP within a few months during the follow-up period after SBRT.

  17. Dentin hypersensitivity clinical study comparing LILT and LEDT keeping the same irradiation parameters

    International Nuclear Information System (INIS)

    Lizarelli, R F Z; Miguel, F A C; Bagnato, V S; Freitas-Pontes, K M; Villa, G E P; Nunez, S C

    2010-01-01

    Dentin hypersensitivity is a common condition associated with high dental pain. A new LED-based (light emitting diode) light source has been used as an experimental tool in some studies. Purpose: The main objective was to compare these two light sources emitting in the same spectral band (red – from 625 to 660 nm) to promote pain relief. Material and methods: A total of 6 sessions were accomplished, being three irradiation sessions and three follow-up sessions. This single-blind study compared a control group (Placebo) and two other groups with different equipments: low laser intensity treatment (LILT) and a light emitting diode system treatment (LEDT). Results: The results showed that there is no statistical difference between LILT and LEDT groups, however, both were better than control group (p ≤ 0.01) in terms of treatment efficiency; there is no difference between the second and the third sessions for both treatment, it means that the third session was not necessary; finally, the improvement at the end of the entire research (follow up care of 30 days) was very expressive in comparison to pre-treatment situation for all teeth (p ≤ 0.01). Conclusion: LILT and LEDT were equally effective to treat dentine hypersensitivity, a 3rd treatment session was not necessary/two sessions are enough

  18. A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans.

    Science.gov (United States)

    Reitz, Marie-Céline; Hrncic, Dragan; Treede, Rolf-Detlef; Caspani, Ombretta

    2016-06-01

    The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P pain models (P pain sensitivity, but probe size and shape should be standardized. Hypersensitivity to blunt pressure-the leading positive sensory sign after peripheral nerve injury in humans-is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species.

  19. Preliminary analysis of the risk factors for radiation pneumonitis in patients with non- small-cell lung cancer treated with concurrent erlotinib and thoracic radiotherapy

    Directory of Open Access Journals (Sweden)

    Zhuang H

    2014-05-01

    Full Text Available Hongqing Zhuang,* Hailing Hou,* Zhiyong Yuan, Jun Wang, Qingsong Pang, Lujun Zhao, Ping WangDepartment of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, and Tianjin Lung Cancer Center, Tianjin, People's Republic of China*These authors contributed equally to this workPurpose: The aim of this study was to investigate radiation pneumonitis and its associated risk factors in patients with non-small-cell lung cancer treated with concurrent erlotinib and thoracic radiotherapy.Materials and methods: We conducted an analysis of patients with nonoperable stage IIIA–IV non-small-cell lung cancer who were treated with concurrent thoracic radiotherapy and erlotinib (ClinicalTrials.gov identifier: NCT00973310. The Common Terminology Criteria for Adverse Events version 3.0 grading system was applied to evaluate the incidence of radiation pneumonitis. The lung dosimetric parameters were recorded in accordance with the treatment plan, and the study endpoint was radiation pneumonitis at grade 2 or more.Results: Among the 24 selected clinical cases, nine were identified with radiation pneumonitis of grade 2 or above (37.5%. This included four cases with grade 2 (16.7%, two cases with grade 3 (8.3%, and three cases with grade 5 (12.5%. The results showed that the planning target volume was a significant factor affecting the incidence of radiation pneumonitis. All lung dosimetric parameters exhibited statistically significant differences between patients with pneumonitis and patients without pneumonitis. The receiver operating characteristic (ROC curve analysis showed that all lung dosimetric parameters were useful in predicting the incidence of radiation pneumonitis. In addition, the threshold values of V5, V10, V15, V20, V30, and mean lung dose were >4%, >29%, >27%, >22%, >17% and >1,027 cGy, respectively.Conclusion: Special attention

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    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

  1. Investigation of the relationship between gross tumor volume location and pneumonitis rates using a large clinical database of non-small-cell lung cancer patients.

    Science.gov (United States)

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

    2012-04-01

    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. 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. 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. 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 in the fit of the pneumonitis model. Copyright

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

    Science.gov (United States)

    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.

  3. ATM status of the clinically radio-hypersensitive

    International Nuclear Information System (INIS)

    Clarke, R. A.; Hasnain, H.; Goozee, G.; Alvandi, R.; Miller, A.; Kearsley, J.H.; Farrell, A.; Bittell, G.; Chen, P.; Lavin, M.

    1996-01-01

    The aim of this study was to characterise the response to ionising radiation of normal tissues from patients that display early and acute hypersensitivity to radiotherapy. Methods include cell proliferation assay using MTT, induced chromosomal aberration testing, cell cycle response to radiation via FACs, mutation analysis of Ataxia Telangiectasia (AT) gene, p53 and AT Western analysis. It is now well appreciated that standard clinical doses (1.8-2 Gy per fraction per day) produce predictable acute and late toxicity in most patients. Occasionally, however, the standard clinical dose produces acute and late toxicity which can exceed the norm both in their extent and timing. The study confirmed the innate cellular radiosensitivity of the clinically radio-hypersensitive patients. No indication of AT gene mutations was found

  4. Hypersensitivity to mosquito bite manifested as Skeeter syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Pérez-Vanzzini

    2015-02-01

    Full Text Available The reactions to mosquito bites are immunological reactions with involvement of IgE, IgG and T cells mediated hypersensitivity. These reactions are common and range from small local reactions, large local reactions to systemic allergic reactions. Skeeter syndrome is defined as a large local induced inflammatory reaction to mosquito bite and sometimes accompanied by systemic symptoms such as fever and vomiting. Diagnosis is based on clinical history and physical examination, supported by the identification of specific IgE by skin testing. Treatment includes prevention, antihistamines and steroids in some cases. Specific immunotherapy still requires further study. This paper reports two cases of patients with hypersensitivity reactions to mosquito bites, which were evaluated in our center presenting positive skin tests.

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

    Science.gov (United States)

    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.

  6. Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

    Science.gov (United States)

    Ding, Hao; Liu, Xiao-Chang; Mei, Qiao; Xu, Jian-Ming; Hu, Xiang-Yang; Hu, Jing

    2014-04-07

    Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.

  7. The Prevalence of food hypersensitivity in young adults

    DEFF Research Database (Denmark)

    Østerballe, Morten; Mørtz, Charlotte G; Hansen, Tine Kjær

    2009-01-01

    by questionnaire, skin prick test (SPT) and histamin release (HR) followed by oral challenge to the most common allergenic foods. FHS was divided into primary and secondary FHS. Primary FHS was defined as being independent of pollen sensitization, whereas secondary FHS was defined as reactions to pollen related......Osterballe M, Mortz CG, Hansen TK, Andersen KE, Bindslev-Jensen C. The Prevalence of food hypersensitivity in young adults. Pediatr Allergy Immunol 2009. (c) 2009 The Authors Journal compilation (c) 2009 John Wiley & Sons A/SA rising prevalence of food hypersensitivity (FHS) and severe allergic...... reactions to foods have been reported in the last decade. However, little is known on the prevalence in young adults. This study estimated the prevalence of FHS to the most common allergenic foods in an unselected population of young adults. We investigated a cohort of 1272 young adults 22 years of age...

  8. Old, new and hidden causes of perioperative hypersensitivity

    DEFF Research Database (Denmark)

    Garvey, Lene Heise

    2016-01-01

    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...... 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....

  9. [Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

    Science.gov (United States)

    Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

    2016-06-01

    Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  10. Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions.

    Science.gov (United States)

    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.

  11. Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague.

    Science.gov (United States)

    Arnaboldi, Paul M; Sambir, Mariya; D'Arco, Christina; Peters, Lauren A; Seegers, Jos F M L; Mayer, Lloyd; McCormick, Alison A; Dattwyler, Raymond J

    2016-11-11

    Yersinia pestis, one of history's deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y. pestis virulence factors, F1 and LcrV, demonstrated variable levels of protection in primate pneumonic plague models. As the most likely mode of exposure in biological attack with Y. pestis is by aerosol, this raises a question of whether this parenteral vaccine will adequately protect humans against pneumonic plague. In the present study we evaluated two distinct mucosal delivery platforms for the intranasal (IN) administration of LcrV and F1 vaccine proteins, a live bacterial vector, Lactobacillus plantarum, and a Tobacco Mosaic Virus (TMV) based delivery platform. IN administration of L. plantarum expressing LcrV, or TMV-conjugated to LcrV and F1 (TMV-LcrV+TMV-F1) resulted in the similar induction of high titers of IgG antibodies and evidence of proinflammatory cytokine secretion. However, only the TMV-conjugate delivery platform protected against subsequent lethal challenge with Y. pestis. TMV-LcrV+TMV-F1 co-vaccinated mice had no discernable morbidity and no mortality, while mice vaccinated with L. plantarum expressing LcrV or rLcrV+rF1 without TMV succumbed to infection or were only partially protected. Thus, TMV is a suitable mucosal delivery platform for an F1-LcrV subunit vaccine that induces complete protection against pneumonic infection with a lethal dose of Y. pestis in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Induction of Hypozincemia and Hepatic Metallothionein Synthesis in Hypersensitivity Reactions.

    Science.gov (United States)

    1978-06-19

    cells to produce endogenous pyrogen (EP), the mediator of febrile response. Controversial evidence exists, however , concerning the differentiation of LEM...hypersensitivity reactions, Kampschmid t and Pulliam (1) proposed that leukocytic endogenous mediator (LEN) is released from phagocytic cells after... endogenous mediator(s) such as LEN, no conclusive evidence is available to indicate a mRNA requirement for the production of potential mediator(s

  13. Early detection of drug-induced pneumonitis by gallium-67 lung scan in six patients with normal chest radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, H; Sawa, H; Takashima, S [Osaka City Univ. (Japan). Hospital

    1981-06-01

    Increased pulmonary accumulation of Gallium-67-citrate was observed in 6 patients (4 with malignant lymphoma, 1 with uterine cancer and 1 with acute myelocytic leukemia) preceding the appearance of any abnormal findings in both chest X-ray and blood gas data. All of them had received multiple courses of chemotherapy. In these patients, the anticancer drugs were administered for 13 to 22 weeks (mean 15 weeks). One patient with malignant lymphoma showed abnormal /sup 67/Ga lung uptake greater than hepatic activity, 3 patients (malignant lymphoma, 2 and uterine cancer, 1) visualized abnormal /sup 67/Ga lung uptake equal to hepatic activity and 2 cases (malignant lymphoma, 1 and acute myelocytic leukemia, 1) demonstrated abnormal accumulation of /sup 67/Ga in the lung greater than background activity. In 4 patients (3 with malignant lymphoma and 1 with uterine cancer) out of 6, transbronchial lung biopsy obtained after the /sup 67/Ga scans showed non-specific interstitial pneumonitis with infiltration of lymphocytes and macrophages compatible with drug-induced pneumonitis. In the other 2 patients, cytology and cultures were negative and follow up /sup 67/Ga lung scans revealed a reduction in intensity of uptake after treatment with corticosteroid. Therefore, we considered that the /sup 67/Ga lung scan was useful for early detection of drug-induced pneumonitis.

  14. Nickel-induced hypersensitivity: etiology, immune reactions, prevention and therapy.

    Science.gov (United States)

    Hostýnek, Jurij J

    2002-08-01

    As a contact allergen causing type I and type IV hypersensitivity, mediated by reagins and allergen-specific T lymphocytes, expressed in a wide range of cutaneous eruptions following dermal or systemic exposure, nickel has acquired the distinction of being among the most frequent causes of hypersensitivity, occupationally as well as among the general population. In synoptic form the many effects that nickel has on the organism are presented, to provide a comprehensive picture of the aspects of that metal with many biologically noxious, but metallurgically indispensable characteristics. This paper reviews the epidemiology, the prognosis for occupational and non-occupational nickel allergic hypersensitivity (NAH), the many types of exposure and the resulting immune responses, immunotoxicity and rate of diffusion through the skin. Alternatives towards prevention and remediation, topical and systemic, for this pervasive and increasing form of morbidity resulting from multiple types of exposure are discussed. Merits and limitations of preventive measures in industry and private life are considered, as well as the effectiveness of topical and systemic therapy in treating NAH.

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

    Science.gov (United States)

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

    2015-08-01

    Hypersensitivity to the chicken egg is a widespread disorder mainly affecting 1-2% of children worldwide. It is the second most common food allergy in children, next to cow's milk allergy. Egg allergy is mainly caused by hypersensitivity to four allergens found in the egg white; ovomucoid, ovalbumin, ovotransferrin and lysozyme. However, some research suggests the involvement of allergens exclusively found in the egg yolk such as chicken serum albumin and YGP42, which may play a crucial role in the overall reaction. In egg allergic individuals, these allergens cause conditions such as itching, atopic dermatitis, bronchial asthma, vomiting, rhinitis, conjunctivitis, laryngeal oedema and chronic urticaria, and anaphylaxis. Currently there is no permanent cure for egg allergy. Upon positive diagnosis for egg allergy, strict dietary avoidance of eggs and products containing traces of eggs is the most effective way of avoiding future hypersensitivity reactions. However, it is difficult to fully avoid eggs since they are found in a range of processed food products. An understanding of the mechanisms of allergic reactions, egg allergens and their prevalence, egg allergy diagnosis and current treatment strategies are important for future studies. This review addresses these topics and discusses both egg white and egg yolk allergy as a whole. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Suspected zonisamide-related anticonvulsant hypersensitivity syndrome in a cat.

    Science.gov (United States)

    Collinet, Audrey; Sammut, Veronique

    2017-12-15

    CASE DESCRIPTION A 2-year-old neutered male domestic shorthair cat was evaluated for sudden onset of cluster seizures. CLINICAL FINDINGS At an emergency clinic, the cat had hyperimmunoglobulinemia and thrombocytopenia. On referral, treatment with levetiracetam, zonisamide, and phenobarbital initially provided good control of cluster seizure activity (attributable to epilepsy of unknow origin). Two weeks later, assessments revealed that serum phenobarbital concentration was within the ideal range but serum zonisamide concentration exceeded the recommended therapeutic range. The dosage of zonisamide was therefore decreased. Four days after dosage reduction, the cat developed generalized lymphadenopathy. Cytologic analysis of lymph node aspirate samples revealed a heterogeneous population of well-differentiated lymphocytes, interpreted as marked reactivity. Although neoplasia could not be ruled out, hypersensitivity to phenobarbital was suspected, and this treatment was discontinued. TREATMENT AND OUTCOME Despite cessation of phenobarbital administration, generalized peripheral lymphadenopathy progressed and hyperglobulinemia and cytopenias developed. These abnormalities resolved after discontinuation of zonisamide administration. The cat remained seizure free with no recurrence of the aforementioned concerns after reinstitution of phenobarbital treatment. CLINICAL RELEVANCE To the authors' knowledge, this is the first reported case of zonisamide-related lymphadenopathy, hyperglobulinemia, and cytopenias in a cat. Anticonvulsant hypersensitivity syndrome is well documented in human medicine, but little information has been published in the veterinary medical literature. Although the effects of anticonvulsant hypersensitivity syndrome in this cat were serious, these effects were reversible with treatment discontinuation.

  17. Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children

    Directory of Open Access Journals (Sweden)

    Kidon Mona

    2007-12-01

    Full Text Available Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction after ASA challenge is seen in 0 to 22% of asthmatic children so challenged, ibuprofen at antipyretic doses may cause acute respiratory problems only in a very small number of mild to moderate asthmatics. The recently elucidated mechanism of action of acetaminophen may explain some occurrences of adverse reactions in patients with cross-reactive NSAID hypersensitivity on the basis of its inhibitory activity on the newly described enzyme, cyclooxygenase (COX-3. This nonspecific sensitivity to inhibition of COX is most likely genetically determined and shows a remarkable association with atopic disease even in the very young age group and possibly an increased predilection in specific ethnic groups. This review summarizes state-of-the-art published data on NSAID hypersensitivity in preschool children.

  18. Linezolid desensitization for a patient with multiple medication hypersensitivity reactions.

    Science.gov (United States)

    Bagwell, Autumn D; Stollings, Joanna L; White, Katie D; Fadugba, Olajumoke O; Choi, Jane J

    2013-01-01

    To describe a case in which a linezolid desensitization protocol was successfully used for a polymicrobial surgical wound infection in a patient with multiple drug hypersensitivity reactions. A 24-year-old woman with vocal cord dysfunction requiring tracheostomy was admitted for a surgical wound infection following a tracheostomy fistula closure procedure. The patient reported multiple antibiotic allergies including penicillins (rash), sulfonamides (rash), vancomycin (anaphylaxis), azithromycin (rash), cephalosporins (anaphylaxis), levofloxacin (unspecified), clindamycin (unspecified), and carbapenems (unspecified). Gram stain of the purulent wound drainage demonstrated mixed gram-negative and gram-positive flora, and bacterial cultures were overgrown with Proteus mirabilis, which precluded identification of other pathogens. Following failed test doses of linezolid, tigecycline, and daptomycin, all of which resulted in hypersensitivity reactions, a 16-step linezolid desensitization protocol was developed and successfully implemented without adverse reactions. The patient completed a 2-week course of antibiotic therapy that included linezolid upon finishing the desensitization protocol. Linezolid is useful in treating complicated and uncomplicated skin and soft tissue infections caused by gram-positive bacteria. With precautions, including premedication, a monitored nursing unit, and immediate availability of an emergency anaphylaxis kit, drug desensitization allows patients the ability to safely use medications to which they may have an immediate hypersensitivity reaction. Minimal data exist on linezolid desensitization protocols. Linezolid desensitization can be a viable option in patients requiring antimicrobial therapy for complicated gram-positive skin infections.

  19. Factors predicting radiation pneumonitis in lung cancer patients: a retrospective study

    International Nuclear Information System (INIS)

    Rancati, T.; Ceresoli, G.L.; Gagliardi, G.; Schipani, S.; Cattaneo, G.M.

    2003-01-01

    Purpose: To evaluate clinical and lung dose-volume histogram based factors as predictors of radiation pneumonitis (RP) in lung cancer patients (PTs) treated with thoracic irradiation. Methods and materials: Records of all lung cancer PTs irradiated at our Institution between 1994 and 2000 were retrospectively reviewed. Eighty-four PTs with small or non-small-cell lung cancer, irradiated at >40 Gy, with full 3D dosimetry data and a follow-up time of >6 months from start of treatment, were analysed for RP. Pneumonitis was scored on the basis of SWOG toxicity criteria and was considered a complication when grade≥II. The following clinical parameters were considered: gender, age, surgery, chemotherapy agents, presence of chronic obstructive pulmonary disease (COPD), performance status. Dosimetric factors including prescribed dose (D iso ), presence of final conformal boost, mean lung dose (D mean ), % of lung receiving ≥20, 25, 30, 35, 40, and 45 Gy (respectively V 20 →V 45 ), and normal tissue complication probability (NTCP) values were analysed. DVHs data and NTCP values were collected for both lungs considered as a paired organ. Median and quartile values were taken as cut-off for statistical analysis. Factors that influenced RP were assessed by univariate (log-rank) and multivariate analyses (Cox hazard model). Results: There were 14 PTs (16.6%) who had ≥grade II pulmonary toxicity. In the entire population, the univariate analysis revealed that many dosimetric parameters (D iso , V 20 , V 30 , V 40 , V 45 ) were significantly associated with RP. No significant correlation was found between the incidence of RP and D mean or NTCP values. Multivariate analysis revealed that the use of mitomycin (MMC) (P=0.005) and the presence of COPD (P=0.026) were the most important risk factor for RP. In the group without COPD (55 PTs, seven RP) a few dosimetric factors (D mean , V 20 , V 45 ) and NTCP values (all models) were associated with RP in the univariate analysis

  20. Reduction of radiation pneumonitis by V20-constraints in breast cancer

    International Nuclear Information System (INIS)

    Goldman, Ulla Blom; Wennberg, Berit; Svane, Gunilla; Bylund, Håkan; Lind, Pehr

    2010-01-01

    Adjuvant local-regional radiotherapy (LRRT) is routinely recommended for breast cancer patients. It is well known being related to pulmonary side-effects. We studied post-RT radiological changes on X-ray and CT, and correlated the findings with Quality of Life (QoL), common dosimetric factors and co-variates. The results were compared with a previously reported cohort of 137 irradiated women. 88 women underwent chest X-ray and CT pre-and 4-5 months after 3-D planned LRRT, minimizing the dose to the ipsilateral lung to V 20 < 30%. The lung field was divided into 3 regions and the development of post-RT density changes were graded (0-3). Patients with radiological changes were compared with non-responders. Clinical symptoms were registered and data on patient and treatment related co-variates were gathered prospectively. The ipsilateral lung dosimetric factors V 13 , V 20 , V 30 and mean dose were calculated and QoL was assessed before and 4 months after RT. The use of dose-volume constraints significally reduced moderate-severe radiological changes on chest X-ray compared with our earlier study (Chi square trend test: p < 0.001). Symptomatic pneumonitis was also rare in the present study. No agreement was found between CT and chest X-ray as diagnostic tools for post-RT pneumonitis. V 13 correlated independently with radiological changes on CT (logistic regression: p = 0.04; ROC area: 0.7). The Co-variates smoking habits, age, chemotherapy, endocrine or trastuzumab therapy did not influence the outcome on multivariate analysis. QoL changes in physical function, i.e. fatigue, dyspnoea were not detected but there was a trend for a worse recovery after chemotherapy in patients with high V 13 (Spearman Rank Correlation: p < 0.05). The use of dose-volume constraints significantly reduced post-RT radiological changes on chest X-ray in LRRT for BC. The lung changes on CT were also generally limited when we used this strategy and was not always picked up on chest X

  1. [Clinical study of the effect of preventing dentine hypersensitiveness by using Fluor Protector and Green Or on the prepared vital pulp abutment teeth].

    Science.gov (United States)

    Qin, Jia-nan; Lu, Yu-miao; Zhou, Xiao-yan

    2005-04-01

    To study and evaluate the effect preventing dentine hypersensitiveness by using Fluor Protector or Green Or on the prepared vital pulp abutment teeth of PFM bridges. 118 cases, 246 prepared vital pulp abutment teeth, were randomly divided into three groups: Experimental Group A--treated with the Fluor Protector and temporary crown; Experimental Group B--treated with the Green Or and temporary crown, and Control Group--only using temporary crown. The results of desensitization in 3 groups were evaluated. F test was used for analysis (DSPV6.01). Significant differences were found between experimental Group A, B and the control group after 1 week (when cementing the PFM bridges); and also after 1 month (P0.05). The effect of preventing dental hypersensitiveness by using Fluor Protector or Green Or on the prepared vital pulp abutment teeth of PFM bridges is ideal. It is easy to use and worth being widely applied.

  2. Hypersensitivity to Contingent Behavior in Paranoia: A New Virtual Reality Paradigm.

    Science.gov (United States)

    Fornells-Ambrojo, Miriam; Elenbaas, Maaike; Barker, Chris; Swapp, David; Navarro, Xavier; Rovira, Aitor; Sanahuja, Josep Maria Tomàs; Slater, Mel

    2016-02-01

    Contingency in interpersonal relationships is associated with the development of secure attachment and trust, whereas paranoia arises from the overattribution of negative intentions. We used a new virtual reality paradigm to experimentally investigate the impact of contingent behavior on trust along the paranoia continuum. Sixty-one healthy participants were randomly allocated to have a social interaction with a pleasant virtual human (avatar) programmed to be highly responsive or not (high/low contingency). Perceived trustworthiness and trusting behavior were assessed alongside control variables attachment and anxiety. Higher paranoia and dismissive attachment were associated with larger interpersonal distances. Unexpectedly, extremely paranoid individuals experienced the highly contingent avatar as more trustworthy than their low contingency counterpart. Higher dismissive attachment was also associated with more subjective trust in both conditions. Extreme paranoia is associated with hypersensitivity to noncontingent behavior, which might explain experiences of mistrust when others are not highly responsive in everyday social situations.

  3. Chest radiographic features of lymphocytic interstitial pneumonitis in HIV-infected children

    Energy Technology Data Exchange (ETDEWEB)

    Pitcher, R.D., E-mail: pitcher@iafrica.co [Division of Paediatric Radiology, Red Cross War Memorial Children' s Hospital, Department of Radiation Medicine, University of Cape Town (South Africa); Beningfield, S.J. [Division of Radiology, New Groote Schuur Hospital and University of Cape Town (South Africa); Zar, H.J. [Department of Paediatric Pulmonology, Red Cross War Memorial Children' s Hospital, School of Child and Adolescent Health, University of Cape Town (South Africa)

    2010-02-15

    Aim: To review the radiological features of biopsy-proven lymphocytic interstitial pneumonitis (LIP) in human immunodeficiency virus (HIV)-infected children and establish whether these are based on systematic radiological analysis, and to investigate whether more specific radiological diagnostic criteria can be developed. Materials and methods: A Medline search of English-language articles on the radiological features of biopsy-proven LIP in HIV-infected children was conducted for the period 1982 to 2007 inclusive. Radiological findings were compared with the Centers for Disease Control and Prevention (CDC) criteria for a presumptive diagnosis of LIP. Results: Pulmonary pathology was recorded as 'diffuse' and 'bilateral' in 125 (97.6%) of 128 reported cases of LIP. Twenty-five different terms were used to describe the pulmonary parenchyma. In 96 (75%), the terminology was consistent with CDC diagnostic criteria. Radiological evolution was documented in 43 (33.5%). Persistent focal opacification superimposed on diffuse pulmonary nodularity was demonstrated in 10 (7.8%). The method of radiological evaluation was described in six (4.6%). In no instance was the terminology defined. Conclusion: The radiological features of LIP have not been systematically analysed. However, CDC criteria remain reliable, allowing diagnosis of at least 75% of cases. The sensitivity of these criteria may be increased by including cases with persistent focal pulmonary opacification superimposed on diffuse nodularity. Longitudinal studies utilizing standardized radiographic analysis are needed to elucidate the natural history of LIP.

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

    Directory of Open Access Journals (Sweden)

    Abidullah Khan

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

    1983-01-01

    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

  6. Proton therapy radiation pneumonitis local dose–response in esophagus cancer patients

    International Nuclear Information System (INIS)

    Echeverria, Alfredo E.; McCurdy, Matthew; Castillo, Richard; Bernard, Vincent; Ramos, Natalia Velez; Buckley, William; Castillo, Edward; Liu, Ping; Martinez, Josue; Guerrero, Thomas

    2013-01-01

    Purpose: This study quantifies pulmonary radiation toxicity in patients who received proton therapy for esophagus cancer. Materials/methods: We retrospectively studied 100 esophagus cancer patients treated with proton therapy. The linearity of the enhanced FDG uptake vs. proton dose was evaluated using the Akaike Information Criterion (AIC). Pneumonitis symptoms (RP) were assessed using the Common Toxicity Criteria for Adverse Events version 4.0 (CTCAEv4). The interaction of the imaging response with dosimetric parameters and symptoms was evaluated. Results: The RP scores were: 0 grade 4/5, 7 grade 3, 20 grade 2, 37 grade 1, and 36 grade 0. Each dosimetric parameter was significantly higher for the symptomatic group. The AIC winning models were 30 linear, 52 linear quadratic, and 18 linear logarithmic. There was no significant difference in the linear coefficient between models. The slope of the FDG vs. proton dose response was 0.022 for the symptomatic and 0.012 for the asymptomatic (p = 0.014). Combining dosimetric parameters with the slope did not improve the sensitivity or accuracy in identifying symptomatic cases. Conclusions: The proton radiation dose response on FDG PET/CT imaging exhibited a predominantly linear dose response on modeling. Symptomatic patients had a higher dose response slope

  7. Chest radiographic features of lymphocytic interstitial pneumonitis in HIV-infected children

    International Nuclear Information System (INIS)

    Pitcher, R.D.; Beningfield, S.J.; Zar, H.J.

    2010-01-01

    Aim: To review the radiological features of biopsy-proven lymphocytic interstitial pneumonitis (LIP) in human immunodeficiency virus (HIV)-infected children and establish whether these are based on systematic radiological analysis, and to investigate whether more specific radiological diagnostic criteria can be developed. Materials and methods: A Medline search of English-language articles on the radiological features of biopsy-proven LIP in HIV-infected children was conducted for the period 1982 to 2007 inclusive. Radiological findings were compared with the Centers for Disease Control and Prevention (CDC) criteria for a presumptive diagnosis of LIP. Results: Pulmonary pathology was recorded as 'diffuse' and 'bilateral' in 125 (97.6%) of 128 reported cases of LIP. Twenty-five different terms were used to describe the pulmonary parenchyma. In 96 (75%), the terminology was consistent with CDC diagnostic criteria. Radiological evolution was documented in 43 (33.5%). Persistent focal opacification superimposed on diffuse pulmonary nodularity was demonstrated in 10 (7.8%). The method of radiological evaluation was described in six (4.6%). In no instance was the terminology defined. Conclusion: The radiological features of LIP have not been systematically analysed. However, CDC criteria remain reliable, allowing diagnosis of at least 75% of cases. The sensitivity of these criteria may be increased by including cases with persistent focal pulmonary opacification superimposed on diffuse nodularity. Longitudinal studies utilizing standardized radiographic analysis are needed to elucidate the natural history of LIP.

  8. Incidence of radiation pneumonitis after thoracic irradiation: Dose-volume correlates

    International Nuclear Information System (INIS)

    Schallenkamp, John M.; Miller, Robert C.; Brinkmann, Debra H.; Foote, Tyler; Garces, Yolanda I.

    2007-01-01

    Purpose: To define clinical and dosimetric parameters correlated with the risk of clinically relevant radiation pneumonitis (RP) after thoracic radiotherapy. Methods and Materials: Records of consecutive patients treated with definitive thoracic radiotherapy were retrospectively reviewed for the incidence of RP of Grade 2 or greater by the Common Toxicity Criteria. Dose-volume histograms using total lung volume (TL) and TL minus gross tumor volume (TL-G) were created with and without heterogeneity corrections. Mean lung dose (MLD), effective lung volume (V eff ), and percentage of TL or TL-G receiving greater than or equal to 10, 13, 15, 20, and 30 Gy (V10-V30, respectively) were analyzed by logistic regression. Receiver operating characteristic (ROC) curves were generated to estimate RP predictive values. Results: Twelve cases of RP were identified in 92 eligible patients. Mean lung dose, V10, V13, V15, V20, and V eff were significantly correlated to RP. Combinations of MLD, V eff , V20, and V30 lost significance using TL-G and heterogeneity corrections. Receiver operating characteristic analysis determined V10 and V13 as the best predictors of RP risk, with a decrease in predictive value above those volumes. Conclusions: Intrathoracic radiotherapy should be planned with caution when using radiotherapy techniques delivering doses of 10 to 15 Gy to large lung volumes

  9. A prospective study of whether radiation pneumonitis is influenced by low-dose irradiated lung volume in primary lung cancer with chronic pulmonary disease

    International Nuclear Information System (INIS)

    Niibe, Yuzuru; Hayakawa, Kazushige; Masuda, Noriyuki; Yoshimura, Hirokuni

    2007-01-01

    The current study prospectively investigated the optimal dose-volume condition in cases of lung cancer with chronic pulmonary disease compared to those without chronic pulmonary disease. Cases of primary lung cancer treated with intended curative radiation therapy were registered in the current study. Their fraction size was limited to 2-3 Gy, so-called standard fractionation. They were prescribed a total dose of 60 Gy for non-small cell lung cancer (NSCLC; n=17) and a total dose of 54 Gy for small cell lung cancer (SCLC; n=4). Of the 21 patients enrolled in this study, 4 had chronic pulmonary disease (study arm), and the others had no chronic pulmonary disease (control arm). Seven received chemotherapy. Symptomatic radiation pneumonitis occurred in 5. Of the four patients in the study arm, two (50%) experienced symptomatic radiation pneumonitis; only 3 of the 17 patients in the control arm (17.6%) experienced symptomatic radiation pneumonitis. Furthermore, the median V 20 of patients who experienced symptomatic radiation pneumonitis in the study arm was 14%, which was higher than that of patients with no symptomatic radiation pneumonitis in the study arm, 5.8%. On the other hand, in the control arm, the median V 20 of patients with symptomatic radiation pneumonitis was 14.2%, about the same as that of patients with no symptomatic radiation pneumonitis in the control arm, 15.1%. The current study suggested that, as much as 15% of V 20 , might play an important role in cases of lung cancer with chronic pulmonary disease. (author)

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

    Science.gov (United States)

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

    2013-03-01

    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. 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. 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. 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. Given dentin hypersensitivity's prevalence, clinicians should diagnose it only after

  11. α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats

    Directory of Open Access Journals (Sweden)

    Sun Y

    2017-07-01

    treatment significantly downregulated NaV1.7 and NaV1.8 expression in colon DRGs from rats with diabetes. Conclusion: Our results suggest that ALA plays an analgesic role, which was likely mediated by downregulation of NaV1.7 and NaV1.8 expressions and functions, thus providing experimental evidence for using ALA to treat colonic hypersensitivity in patients with diabetic visceral pain. Keywords: diabetes, colonic hypersensitivity, dorsal root ganglion, voltage-gated sodium channels, α-lipoic acid

  12. Carboplatin hypersensitivity in children with glial tumors: a report of two cases

    Directory of Open Access Journals (Sweden)

    Tugce Kazgan

    2016-12-01

    Full Text Available Carboplatin, commonly used chemotherapeutic agent in treatment of pediatric cancers, can cause life-threatening hypersensitivty reactions. Carboplatin hypersensitivity is protocol-specific and associated with repeated doses and prolonged use of the drug. Vincristin and carboplatin combination is used efficiently in treatment of pediatric low-grade gliomas. However, hypersensitivity reactions are frequently observed during usage of this protocol. Desensitization strategies with variable success rates were reported. Failure of these strategies may lead to cessation of carboplatin Here, we report two cases with carboplatin hypersensitivity treated with epinephrine administration, in whom carboplatin was discontinued after hypersensitivity reaction. [Cukurova Med J 2016; 41(4.000: 796-798

  13. Evaluation of basophil activation test in suspected food hypersensitivity.

    Science.gov (United States)

    Pignatti, Patrizia; Yacoub, Mona-Rita; Testoni, Claudia; Pala, Gianni; Corsetti, Maura; Colombo, Giselda; Meriggi, Antonio; Moscato, Gianna

    2017-07-01

    Food hypersensitivity is characterized by a wide range of symptoms. The relationship between symptoms and food is more frequently suspected than objectively proven. Basophil activation test (BAT) is based on the evaluation of activation markers on blood basophils in vitro stimulated with drugs or allergens. The aim of the study was to evaluate the usefulness of BAT when introduced in the routine work-up of suspected food hypersensitivity. BAT was requested in subjects with food adverse reactions when a discrepancy existed among history and skin prick test (SPT) and/or specific IgE. Data from 150 subjects were analysed using CD63 as basophil activation marker. Thirty controls were evaluated for cut-offs. Immunoblots was performed with the sera of representative subjects positive for BAT and negative for SPT and sIgE. 1,024 BAT were carried out, the agreement (positive/positive and negative/negative) was 78.5% for BAT vs. SPT and 78.3% for BAT vs. IgE. Atopic patients, but not atopic controls, more frequently had a positive BAT than non-atopic patients (P tested food) and both negative sIgE and SPT. Immunoblots revealed the presence of sIgE for the tested foods in representative patients with positive BAT, negative SPT and sIgE. Introduction of BAT in routine of food hypersensitivity, limited to subjects with a discrepancy between history and traditional tests, might be useful particularly when total IgE are low. © 2015 International Clinical Cytometry Society. © 2015 International Clinical Cytometry Society.

  14. Considerations on the electromagnetic hypersensitivity and idiopathic environmental intolerances

    International Nuclear Information System (INIS)

    Perrin, Anne

    2017-01-01

    After having noticed that environmental and health concerns are an important matter of concern in our society, and that always more pathologies are blamed on the environment, the author more particularly addresses electromagnetic hypersensitivity (EHS) which is considered by the WHO as a part of idiopathic environmental intolerances (IEI). He more particularly discusses the various conditions of emergence of these syndromes as they have been noticed, analysed and identified in different countries and in different studies. He discusses the possible definition to be given to these syndromes and their possible meaning

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...... 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....

  16. Electromagnetic hypersensitivity: The opinion of an observer neurologist

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rasha Hammamieh

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

  1. Does Bleomycin Lung Toxicity Increase the Risk of Radiation Pneumonitis in Hodgkin Lymphoma?

    Energy Technology Data Exchange (ETDEWEB)

    Abou Yehia, Zeinab [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mikhaeel, George N. [Department of Clinical Oncology, Guy' s & St Thomas' Hospital, London (United Kingdom); Smith, Grace; Pinnix, Chelsea C.; Milgrom, Sarah A.; Tang, Chad; Jiang, Wen [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fanale, Michelle A.; Oki, Yasuhiro [Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shank, JoAnn H.; Horace, Trisha; Reddy, Jay [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Akhtari, Mani [Department of Radiation Oncology, The University of Texas Medical Branch Hospitals, Galveston, Texas (United States); Gunther, Jillian R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Suki, Tina [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Turner, Shryll [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2016-12-01

    Purpose: Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in patients with Hodgkin lymphoma (HL). We undertook the present study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation therapy (RT) in these patients. Methods and Materials: We identified 123 HL patients treated with ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) followed by RT to the chest from January 2009 to December 2014. The medical records were reviewed for clinical, pathologic, and treatment information and toxicities. Our primary outcome was RP of any grade. Univariate and multivariate analyses were used to assess the association of BPT, baseline patient characteristics, and treatment variables with the incidence of RP. Results: A total of 123 patients were included, of whom 99 (80%) received consolidation intensity modulated RT after ABVD treatment. We identified 31 patients (25.2%) with BPT after frontline ABVD. Seventeen patients (13.8%) developed RP a median of 8 weeks (range 1-39) after RT completion. BPT did not correlate with the risk of developing RP (P=.36). We evaluated the RP outcomes with respect to the bleomycin to RT interval (≤6 weeks vs >6 weeks), and we found that this interval did not predict for RP risk (P=.60). Dosimetric parameters such as the volume covered by 5 Gy and the mean lung dose were analyzed. A volume covered by 5 Gy of >55% and mean lung dose >13.5 Gy increased the risk of RP by 1.14-fold (P=.002) and 4.24-fold (P=.007), respectively. Conclusions: The results of our study suggest that BPT does not increase the risk of developing RP. Furthermore, RT initiation does not need to be delayed after chemotherapy, except to allow for the completion of steroid therapy or clinical recovery from BPT.

  2. Does Bleomycin Lung Toxicity Increase the Risk of Radiation Pneumonitis in Hodgkin Lymphoma?

    International Nuclear Information System (INIS)

    Abou Yehia, Zeinab; Mikhaeel, George N.; Smith, Grace; Pinnix, Chelsea C.; Milgrom, Sarah A.; Tang, Chad; Jiang, Wen; Fanale, Michelle A.; Oki, Yasuhiro; Shank, JoAnn H.; Horace, Trisha; Reddy, Jay; Akhtari, Mani; Gunther, Jillian R.; Suki, Tina; Allen, Pamela K.; Turner, Shryll; Mawlawi, Osama; Dabaja, Bouthaina S.

    2016-01-01

    Purpose: Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in patients with Hodgkin lymphoma (HL). We undertook the present study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation therapy (RT) in these patients. Methods and Materials: We identified 123 HL patients treated with ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) followed by RT to the chest from January 2009 to December 2014. The medical records were reviewed for clinical, pathologic, and treatment information and toxicities. Our primary outcome was RP of any grade. Univariate and multivariate analyses were used to assess the association of BPT, baseline patient characteristics, and treatment variables with the incidence of RP. Results: A total of 123 patients were included, of whom 99 (80%) received consolidation intensity modulated RT after ABVD treatment. We identified 31 patients (25.2%) with BPT after frontline ABVD. Seventeen patients (13.8%) developed RP a median of 8 weeks (range 1-39) after RT completion. BPT did not correlate with the risk of developing RP (P=.36). We evaluated the RP outcomes with respect to the bleomycin to RT interval (≤6 weeks vs >6 weeks), and we found that this interval did not predict for RP risk (P=.60). Dosimetric parameters such as the volume covered by 5 Gy and the mean lung dose were analyzed. A volume covered by 5 Gy of >55% and mean lung dose >13.5 Gy increased the risk of RP by 1.14-fold (P=.002) and 4.24-fold (P=.007), respectively. Conclusions: The results of our study suggest that BPT does not increase the risk of developing RP. Furthermore, RT initiation does not need to be delayed after chemotherapy, except to allow for the completion of steroid therapy or clinical recovery from BPT.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-01-01

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

  4. Clinical validation of the LKB model and parameter sets for predicting radiation-induced pneumonitis from breast cancer radiotherapy

    International Nuclear Information System (INIS)

    Tsougos, Ioannis; Mavroidis, Panayiotis; Theodorou, Kyriaki; Rajala, J; Pitkaenen, M A; Holli, K; Ojala, A T; Hyoedynmaa, S; Jaervenpaeae, Ritva; Lind, Bengt K; Kappas, Constantin

    2006-01-01

    The choice of the appropriate model and parameter set in determining the relation between the incidence of radiation pneumonitis and dose distribution in the lung is of great importance, especially in the case of breast radiotherapy where the observed incidence is fairly low. From our previous study based on 150 breast cancer patients, where the fits of dose-volume models to clinical data were estimated (Tsougos et al 2005 Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy Phys. Med. Biol. 50 3535-54), one could get the impression that the relative seriality is significantly better than the LKB NTCP model. However, the estimation of the different NTCP models was based on their goodness-of-fit on clinical data, using various sets of published parameters from other groups, and this fact may provisionally justify the results. Hence, we sought to investigate further the LKB model, by applying different published parameter sets for the very same group of patients, in order to be able to compare the results. It was shown that, depending on the parameter set applied, the LKB model is able to predict the incidence of radiation pneumonitis with acceptable accuracy, especially when implemented on a sub-group of patients (120) receiving D-bar-bar vertical bar EUD higher than 8 Gy. In conclusion, the goodness-of-fit of a certain radiobiological model on a given clinical case is closely related to the selection of the proper scoring criteria and parameter set as well as to the compatibility of the clinical case from which the data were derived. (letter to the editor)

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

    International Nuclear Information System (INIS)

    Das, Shiva K.; Zhou Sumin; Zhang, Junan; Yin, F.-F.; Dewhirst, Mark W.; Marks, Lawrence B.

    2007-01-01

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

  6. Rice hypersensitive induced reaction protein 1 (OsHIR1) associates with plasma membrane and triggers hypersensitive cell death.

    Science.gov (United States)

    Zhou, Liang; Cheung, Ming-Yan; Li, Man-Wah; Fu, Yaping; Sun, Zongxiu; Sun, Sai-Ming; Lam, Hon-Ming

    2010-12-30

    In plants, HIR (Hypersensitive Induced Reaction) proteins, members of the PID (Proliferation, Ion and Death) superfamily, have been shown to play a part in the development of spontaneous hypersensitive response lesions in leaves, in reaction to pathogen attacks. The levels of HIR proteins were shown to correlate with localized host cell deaths and defense responses in maize and barley. However, not much was known about the HIR proteins in rice. Since rice is an important cereal crop consumed by more than 50% of the populations in Asia and Africa, it is crucial to understand the mechanisms of disease responses in this plant. We previously identified the rice HIR1 (OsHIR1) as an interacting partner of the OsLRR1 (rice Leucine-Rich Repeat protein 1). Here we show that OsHIR1 triggers hypersensitive cell death and its localization to the plasma membrane is enhanced by OsLRR1. Through electron microscopy studies using wild type rice plants, OsHIR1 was found to mainly localize to the plasma membrane, with a minor portion localized to the tonoplast. Moreover, the plasma membrane localization of OsHIR1 was enhanced in transgenic rice plants overexpressing its interacting protein partner, OsLRR1. Co-localization of OsHIR1 and OsLRR1 to the plasma membrane was confirmed by double-labeling electron microscopy. Pathogen inoculation studies using transgenic Arabidopsis thaliana expressing either OsHIR1 or OsLRR1 showed that both transgenic lines exhibited increased resistance toward the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. However, OsHIR1 transgenic plants produced more extensive spontaneous hypersensitive response lesions and contained lower titers of the invading pathogen, when compared to OsLRR1 transgenic plants. The OsHIR1 protein is mainly localized to the plasma membrane, and its subcellular localization in that compartment is enhanced by OsLRR1. The expression of OsHIR1 may sensitize the plant so that it is more prone to HR and hence can react more

  7. Cutaneous and systemic hypersensitivity reactions to metallic implants.

    Science.gov (United States)

    Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C

    2011-01-01

    Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous, and vasculitic eruptions may occur. Also, more complex immune reactions may develop around the implants, resulting in pain, inflammation, and loosening. Nickel, cobalt, and chromium are the three most common metals that elicit both cutaneous and extracutaneous allergic reactions from chronic internal exposure. However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions remains to be fully understood. This review provides an update of the current knowledge in this field and should be valuable to health care providers who manage patients with conditions related to this field.

  8. The Role of Esophageal Hypersensitivity in Functional Heartburn.

    Science.gov (United States)

    Kondo, Takashi; Miwa, Hiroto

    2017-08-01

    Functional heartburn (FH) is defined as a functional esophageal disorder characterized by symptoms of chronic heartburn with no apparent correlation to acid or nonacid reflux. In addition, its symptoms persist despite the lack of organic abnormalities or inflammation, esophageal motility disorders, or metabolic disorders. Although conditions presenting with esophageal symptoms without endoscopic abnormalities were previously categorized as nonerosive reflux disease, such conditions are now classified into 3 categories under Rome IV criteria: nonerosive reflux disease, reflux hypersensitivity, and FH. Although many aspects of FH remain unclear, its onset mechanism is considered to be strongly associated with peripheral or central sensitization, given the fact that its symptoms seem to be unrelated to gastroesophageal reflux. In addition, the cause of such hypersensitivity is an interesting topic in itself, and psychological factors, such as stress followed by increasing esophageal permeability are gaining attention as factors that can potentially influence this condition. There is a great unmet clinical need for therapeutic drugs that can be used to treat FH, and the development of novel drugs, diagnostic tests and biomarkers is eagerly awaited.

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

    Directory of Open Access Journals (Sweden)

    Najeeba Riyaz

    2012-01-01

    Full Text Available 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.

  10. Patch testers' opinions regarding diagnostic criteria for metal hypersensitivity reactions to metallic implants

    DEFF Research Database (Denmark)

    Schalock, Peter C; Thyssen, Jacob P

    2013-01-01

    Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated.......Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated....

  11. Genome-wide association study of insect bite hypersensitivity in swedish-born icelandic horses

    NARCIS (Netherlands)

    Shrestha, M.; Eriksson, S.; Schurink, A.; Andersson, L.S.; Sundquist, M.; Frey, R.; Brostrom, H.; Bergstrom, T.; Ducro, B.J.; lindgren, G.

    2015-01-01

    Insect bite hypersensitivity (IBH) is the most common allergic skin disease in horses and is caused by biting midges, mainly of the genus Culicoides. The disease predominantly comprises a type I hypersensitivity reaction, causing severe itching and discomfort that reduce the welfare and commercial

  12. Baroreflex Sensitivity And Autonomic Nervous System Function In Carotid Sinus Hypersensitivity

    DEFF Research Database (Denmark)

    Brinth, Louise Schouborg; Pors, Kirsten; Theibel, Ann Cathrine

    2015-01-01

    hypersensitivity ranging from reduced to increased sensitivity compared to controls. We wanted to establish whether measures of baroreflex sensitivity and autonomic function differed between patients diagnosed with carotid sinus hypersensitivity and age matched controls. We included 36 patients (12 women; 74 +/-10...... sensitivity may not follow the same neuronal pathways as those responding to the crude external pressures applied during carotid sinus massage...

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

    Science.gov (United States)

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

    2015-09-01

    Vemurafenib and dabrafenib are both orally bioavailable small molecule agents that block mitogen activated protein kinase signalling in patients with melanoma and BRAF(V600E) mutation. Generalized hypersensitivity reactions to vemurafenib or dabrafenib have not been described. Continuing vemurafenib or dabrafenib therapy despite hypersensitivity reaction is especially important in patients with melanoma and BRAF(V600E) mutation, in whom this mutation plays a critical role in tumour growth. Desensitization protocols to overcome hypersensitivity reactions by gradual reintroduction of small amounts of the offending drug up to full therapeutic doses are available for many anti-cancer agents, including vemurafenib but, to the best of our knowledge, have not been reported for dabrafenib. We describe a patient with metastatic melanoma who developed Type I hypersensitivity reaction to vemurafenib and to subsequent treatment with dabrafenib, and who was successfully treated by drug desensitization which allowed safe prolonged continuation of dabrafenib. The development of hypersensitivity reactions for both dabrafenib and vemurafinib in the current case could be because these drugs have a similar chemical structure and cause a cross-reactivity. However, hypersensitivity reaction to a non-medicinal ingredient shared by the two drugs is also possible. Oral desensitization appears to be an option for patients with hypersensitivity Type I to dabrafenib. This approach may permit clinicians to safely administer dabrafenib to patients who experience hypersensitivity reactions to this life-prolonging medication. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Hypersensitive cell death in plants : its mechanisms and role in plant defense against pathogens

    NARCIS (Netherlands)

    Iakimova, E.T.; Michalczuk, L.; Woltering, E.J.

    2005-01-01

    This review is a recent update in the understanding of the hypersensitive response (HR) of plants with special consideration to the physiological and biochemical determinants in different model systems. Hypersensitive response is reviewed as a form of programmed cell death (PCD) representing one of

  15. Detective quantum efficiency gains compared with speed gains for hypersensitized astronomical plates

    International Nuclear Information System (INIS)

    Kaye, A.L.

    1977-01-01

    It is reasonable to assume that gains in detective quantum efficiency (DQE) are far better criteria for assessing the performance of hypersensitizing techniques than gains in speed. It is shown here that gains in speed can be misleading, for some methods of hypersensitization give plates of increased speed but reduced detective quantum efficiency. (author)

  16. Intestinal Fungal Dysbiosis Is Associated With Visceral Hypersensitivity in Patients With Irritable Bowel Syndrome and Rats.

    Science.gov (United States)

    Botschuijver, Sara; Roeselers, Guus; Levin, Evgeni; Jonkers, Daisy M; Welting, Olaf; Heinsbroek, Sigrid E M; de Weerd, Heleen H; Boekhout, Teun; Fornai, Matteo; Masclee, Ad A; Schuren, Frank H J; de Jonge, Wouter J; Seppen, Jurgen; van den Wijngaard, René M

    2017-10-01

    Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in the activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in the development of IBS. We analyzed intestinal mycobiomes of patients with IBS and a rat model of visceral hypersensitivity. We used internal transcribed spacer 1-based metabarcoding to compare fecal mycobiomes of 18 healthy volunteers with those of 39 patients with IBS (with visceral hypersensitivity or normal levels of sensitivity). We also compared the mycobiomes of Long-Evans rats separated from their mothers (hypersensitive) with non-handled (normally sensitive) rats. We investigated whether fungi can cause visceral hypersensitivity using rats exposed to fungicide (fluconazole and nystatin). The functional relevance of the gut mycobiome was confirmed in fecal transplantation experiments: adult maternally separated rats were subjected to water avoidance stress (to induce visceral hypersensitivity), then given fungicide and donor cecum content via oral gavage. Other rats subjected to water avoidance stress were given soluble β-glucans, which antagonize C-type lectin domain family 7 member A (CLEC7A or DECTIN1) signaling via spleen-associated tyrosine kinase (SYK), a SYK inhibitor to reduce visceral hypersensitivity, or vehicle (control). The sensitivity of mast cells to fungi was tested with mesenteric windows (ex vivo) and the human mast cell line HMC-1. α diversity (Shannon index) and mycobiome signature (stability selection) of both groups of IBS patients differed from healthy volunteers, and the mycobiome signature of hypersensitive patients differed from that of normally sensitive patients. We observed mycobiome dysbiosis in rats that had been separated from their mothers compared with non-handled rats. Administration of fungicide to hypersensitive rats reduced their visceral hypersensitivity to normal

  17. National prevalence of asthma and chemical hypersensitivity: an examination of potential overlap.

    Science.gov (United States)

    Caress, Stanley M; Steinemann, Anne C

    2005-05-01

    The objective of this study was to investigate the linkage between asthma and chemical hypersensitivity. The authors conducted a population study with a random sample of 1057 geographically weighted cases to determine the prevalence of both asthma and chemical hypersensitivity in the American population and to explore their co-occurrence. A total of 14.1% of the respondents reported being diagnosed with asthma and 11.2% reported a hypersensitivity to chemicals. Of those with asthma, 27.2% also reported being hypersensitive to chemicals and 7.4% reported also being diagnosed with multiple chemical sensitivities (MCS). Of those diagnosed with MCS, 42% reported also being diagnosed with asthma. Additionally, 29.7% of those with asthma said air fresheners caused breathing difficulties, and 37.2% found scented products irritating. The results indicate that there is significant overlap between some forms of asthma and chemical hypersensitivity.

  18. Linking Anxiety and Insistence on Sameness in Autistic Children: The Role of Sensory Hypersensitivity.

    Science.gov (United States)

    Black, Karen R; Stevenson, Ryan A; Segers, Magali; Ncube, Busiswe L; Sun, Sol Z; Philipp-Muller, Aviva; Bebko, James M; Barense, Morgan D; Ferber, Susanne

    2017-08-01

    Sensory hypersensitivity and insistence on sameness (I/S) are common, co-occurring features of autism, yet the relationship between them is poorly understood. This study assessed the impact of sensory hypersensitivity on the clinical symptoms of specific phobia, separation anxiety, social anxiety and I/S for autistic and typically developing (TD) children. Parents of 79 children completed questionnaires on their child's difficulties related to sensory processing, I/S, and anxiety. Results demonstrated that sensory hypersensitivity mediated 67% of the relationship between symptoms of specific phobia and I/S and 57% of the relationship between separation anxiety and I/S. No relationship was observed between sensory hypersensitivity and social anxiety. These mediation effects of sensory hypersensitivity were found only in autistic children, not in TD children.

  19. Comparative evaluation of Type 1 latex hypersensitivity in patients with chronic urticaria, rubber factory workers and healthy control subjects

    NARCIS (Netherlands)

    Piskin, Gamze; Akyol, Aynur; Uzar, Hatice; Tulek, Necla; Boyvat, Ayse; Gurgey, Erbak

    2003-01-01

    Latex hypersensitivity manifests itself most commonly with contact urticaria. In this study, we investigated the frequency of latex hypersensitivity as a possible aetiological factor in patients with chronic urticaria (CU) and compared latex hypersensitivity of CU patients (n = 50) with that of

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

    Science.gov (United States)

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

    2016-10-01

    Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Shi HS

    2012-05-01

    Full Text Available Hua-shan Shi1,* Xiang Gao,1,3,* Dan Li,1,* Qiong-wen Zhang,1 Yong-sheng Wang,2 Yu Zheng,1 Lu-Lu Cai,1 Ren-ming Zhong,2 Ao Rui,1 Zhi-yong Li,1 Hao Zheng,1 Xian-cheng Chen,1 Li-juan Chen,11State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, People's Republic of China; 2State Key Laboratory of Biotherapy and Department of Thoracic Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China; 3Deparment of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, People's Republic of China*These authors contributed equally to this workAbstract: 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

  3. Effects of Positioning Uncertainty and Breathing on Dose Delivery and Radiation Pneumonitis Prediction in Breast Cancer

    International Nuclear Information System (INIS)

    Mavroidis, Panayiotis; Axelsson, Sofie; Hyoedynmaa, Simo; Rajala, Juha; Pitkaenen, 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

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

    International Nuclear Information System (INIS)

    Sampath, Sagus; Schultheiss, Timothy E.; Wong, Jeffrey

    2005-01-01

    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 α/β value of the linear-quadratic model was estimated to be 2.8 Gy. The dose eliciting a 50% incidence, D 50 , for IP after 120 mg/kg of cyclophosphamide was 8.8 Gy; in the absence of chemotherapy, the estimated D 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. Shielding the lung

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-15

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

  6. Paradoxical effect of pertussis toxin on the delayed hypersensitivity response to autoantigens in mice.

    Directory of Open Access Journals (Sweden)

    Rajwahrdhan Yadav

    2010-08-01

    Full Text Available Pertussis toxin (PTX, an exotoxin of Bordetella pertussis, enhances the development of experimental autoimmune diseases such as experimental autoimmune uveitis (EAU and experimental autoimmune encephalomyelitis (EAE in rodent models. The mechanisms of the promotion of experimental autoimmune diseases by PTX may be based upon PTX-induced disruption of the blood eye/brain barriers facilitating the infiltration of inflammatory cells, the modulation of inflammatory cell migration and the enhancement of the activation of inflammatory cells. We hypothesized that the facilitation of experimental autoimmunity by PTX suggests that its influence on the in vivo immune response to auto-antigen may differ from its influence on non-self antigens.We have evaluated the effect of PTX on the simultaneous generation of delayed type hypersensitivity (DTH responses and autoimmune responses to uveitogenic interphotoreceptor retinoid binding protein peptide (IRBP161-180, encephalitogenic myelin oligodendrocyte glycoprotein peptide (MOG35-55 or ovalbumin (OVA. PTX injection of mice immunized to IRBP peptide161-180 led to (i the development of EAU as shown by histopathology of the retina, (ii pro-inflammatory cytokine production by splenocytes in response to IRBP peptide161-180, and (iii symptomatic EAE in mice immunized with encephalitogenic MOG peptide35-55. However, mice that received PTX had a reduced DTH response to IRBP161-180 peptide or MOG peptide35-55 when challenged distal to the site affected by autoreactive T cells. Moreover, footpad challenge with MOG35-55 peptide reduced EAE in mice immunized with MOG peptide. In contrast, the use of PTX when immunizing with OVA protein or an OVA immunogenic peptide did not affect the DTH response to OVA.The results suggest that that the reduced DTH response in mice receiving PTX may be specific for autoantigens and autoantigen-reactive T cells are diverted away from ectopic sites that received the autoantigen and towards

  7. Adrenergic receptors are a fallible index of adrenergic denervation hypersensitivity

    DEFF Research Database (Denmark)

    Dejgaard, Anders; Liggett, S B; Christensen, N J

    1991-01-01

    In view of evidence that neither interindividual nor induced intra-individual variations of adrenergic receptor status are related to metabolic or haemodynamic sensitivity to adrenaline in vivo, we took an alternative approach to assessment of the relevance of adrenergic receptor measurement...... by measuring these in a group of subjects with well-documented adrenergic denervation hypersensitivity, patients with diabetic autonomic neuropathy. Mononuclear leukocyte beta 2-adrenergic receptor densities (and binding affinities), measured with 125I-labelled pindolol, and isoproterenol-stimulated cyclic AMP...... accumulation, in samples from patients with insulin-dependent diabetes mellitus (IDDM) with diabetic autonomic neuropathy (n = 8), were no different from those in samples from patients with IDDM without neuropathy (n = 8), or from non-diabetic subjects (n = 8). In addition, platelet alpha 2-adrenergic receptor...

  8. Immediate and delayed contact hypersensitivity to verbena plants

    DEFF Research Database (Denmark)

    Potter, P C; Mather, S; Lockey, P

    1995-01-01

    Plants from the Verbenaceae family may cause contact dermatitis of unknown nature. This report describes 2 cases of allergic reactions to the Verbena species. A teenage boy developed an anaphylactic allergic response following contact with the leaves of Verbena hybrida. Characterization...... of the patient's specific IgE response to Verbena hybrida, using Western blots and autoradiography, identified the specific 62000 Dalton allergen present in the verbena leaves to which the patient reacted. This is the first report of an IgE-mediated immediate contact hypersensitivity reaction to Verbena hybrida......, a common perennial in South African gardens. The other case was a 23-year-old female gardener who developed immediate and delayed-type contact dermatitis from Verbena elegans 'Cleopatra' produced in a Danish nursery. Prick tests to plant material were considered positive and of an allergic nature....

  9. Allopurinol-induced Severe Hypersensitivity with Acute Renal Failure

    Directory of Open Access Journals (Sweden)

    I-Hung Chen

    2005-05-01

    Full Text Available A 62-year-old male was sent to the emergency room due to a high fever and generalized skin rash after taking allopurinol for 9 days. Physical examination was normal except for the generalized skin rash presenting with erythematous macules. Complete blood count showed leukocytosis with eosinophilia. Blood biochemistry showed impaired renal and hepatic function. Pathologic examination concluded that the skin rash was erythema multiforme. These findings met the diagnostic criteria for allopurinol-induced hypersensitivity syndrome (AHS. Our patient not only had the most common skin lesion but soon developed acute renal failure that required intermittent hemodialysis, despite rapid discontinuation of allopurinol and adequate hydration and steroid therapy. No other causes of acute renal failure were found. Renal impairment was the worst part of the patient's condition and he never completely recovered. AHS should be considered in the differential diagnosis of acute renal and hepatic failure in patients with evidence of allergy and recent use of allopurinol.

  10. Autophagic components contribute to hypersensitive cell death in Arabidopsis

    DEFF Research Database (Denmark)

    Hofius, Daniel; Schultz-Larsen, Torsten; Joensen, Jan

    2009-01-01

    Autophagy has been implicated as a prosurvival mechanism to restrict programmed cell death (PCD) associated with the pathogen-triggered hypersensitive response (HR) during plant innate immunity. This model is based on the observation that HR lesions spread in plants with reduced autophagy gene...... expression. Here, we examined receptor-mediated HR PCD responses in autophagy-deficient Arabidopsis knockout mutants (atg), and show that infection-induced lesions are contained in atg mutants. We also provide evidence that HR cell death initiated via Toll/Interleukin-1 (TIR)-type immune receptors through...... the defense regulator EDS1 is suppressed in atg mutants. Furthermore, we demonstrate that PCD triggered by coiled-coil (CC)-type immune receptors via NDR1 is either autophagy-independent or engages autophagic components with cathepsins and other unidentified cell death mediators. Thus, autophagic cell death...

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

    Science.gov (United States)

    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.

  12. Desensitization of delayed-type hypersensitivity in mice: suppressive environment

    Directory of Open Access Journals (Sweden)

    Takashi Katsura

    1993-01-01

    Full Text Available The systemic injection of high doses of antigen into a preimmunized animal results in transient unresponsiveness of cell-mediated immune responses. This phenomenon is known as desensitization. Serum interleukin 2 (IL-2 activity was found transiently in desensitized mice at 3 h after the antigen challenge. These mice could not reveal antigen nonspecific delayed-type hypersensitivity (DTH 1 d after the challenge. Specific suppression of DTH was observed at later stages. Sera from 3 h desensitized mice showed suppressive effects on DTH in preo immunized mice. Administration of recombinant IL-2 into preimmunized mice led to the failure of development of DTH to antigens. These observations suggest that IL-2 plays an important role in the suppressive environment.

  13. On the phenomenon of electromagnetic hypersensitivity; Das Phaenomen der Elektrosensibilitaet

    Energy Technology Data Exchange (ETDEWEB)

    David, E.; Reissenweber, J.; Wojtysiak, A.; Pfotenhauer, M. [Witten-Herdecke Univ., Witten (Germany). Inst. fuer Normale und Pathologische Physiologie; Witten-Herdecke Univ., Witten (Germany). Zentrum fuer Elektropathologie

    2002-07-01

    For more than fifteen years electromagnetic fields (EMFs) are intensively discussed in connection with health hazards in mass media as well as questions of standard setting by the authorities. The present elaboration gives an extended overview over the actual situation of the special electromagnetic hypersensitivity issue in relation to electromagnetic field research in the international scientific community. There are parallels and analogies between the symptoms of electromagnetic hypersensitivity and those of the Multiple-Chemical-Sensitivity-Syndrome and other environmental diseases. The first part deals with the biophysical fundamental knowledge of interactions between electromagnetic fields and biological systems such as man or animal including threshold values and threshold philosophy. Then hypothetical mechanisms of action of EMF are demonstrated, with a special focus on the melatonin hypothesis, which has not been proved in all its parts up to now. Additionally, in the context of our biomedical research into disorders of well-being we conducted an analysis of written and telephone questions about the EMF issue which are sent to our center. The results are of scientific and political interest and are demonstrated in detail. (orig.) [German] Das Phaenomen der Elektrosensibilitaet gewinnt zunehmend an Bedeutung innerhalb der Diskussion um die medizinisch-biologischen Wirkungen elektromagnetischer Felder. Es konnte bisher nicht nachgewiesen werden, dass die Elektrosensibilitaet/Magnetosensibilitaet als eigenstaendige Krankheitseinheit (Krankheitsentitaet) existiert. Es handelt sich dabei um ein Phaenomen, das vor etwa 15 Jahren benannt und zunaechst nicht ernst genommen wurde. Im Rahmen des relativ jungen medizinisch-biologischen Fachgebietes Elektropathologie scheinen weitere Untersuchungen erforderlich, um die teilweise auch widerspruechlichen Befunde aufzuklaeren und zu erfahren, ob Felder Befindlichkeitsstoerungen ausloesen koennen, die in aehnlicher Form

  14. The scientific rationale and development of an optimized dentifrice for the treatment of dentin hypersensitivity.

    Science.gov (United States)

    Tavss, Edward A; Fisher, Steven W; Campbell, Shannon; Bonta, Yolanda; Darcy-Siegel, Joann; Blackwell, Bernie L; Volpe, Anthony R; Miller, Steven E

    2004-02-01

    To describe the development of a new dentin hypersensitivity treatment, Colgate Sensitive Maximum Strength dentifrice, containing 5% potassium nitrate as the anti-hypersensitivity active agent. The objective was to develop a home-use hypersensitivity dentifrice that would be superior to the market leader, improving on what is available, which also contains 5% potassium nitrate as the anti-hypersensitivity active agent. In vivo (clinicals, taste evaluation and rat caries), in vitro (potassium flux) and analytical (rheology, dispensed volume, scanning electron microscopy, electron scanning chemical analysis and radioactive dentin abrasion) methods were performed. The objective was accomplished with the development of a new activated silica technology that resulted in enhanced potassium ion activity. In vitro documentation, supported by clinical studies, demonstrated that the resulting formula is more effective than the market leader for relief of hypersensitivity pain. Fast pain relief in less than 2 weeks and long-lasting protection against pain with regular use have also been clinically documented. Furthermore, FDA-required in vivo and in vitro studies indicate that this formula, which contains 0.45% stannous fluoride (1100 ppm fluoride) as the anti-caries active agent, is effective against caries. Good taste, acceptable rheology, acceptable abrasivity, and cosmetic and chemical stability have all been engineered into this unique dentin hypersensitivity treatment. In summary, a highly efficacious consumer friendly treatment for dentin hypersensitivity has been developed.

  15. Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies.

    Science.gov (United States)

    Tai, Yu-Hsiao; Tai, Yi-Jou; Hsu, Heng-Cheng; Lee, Shu-Ping; Chen, Yun-Yuan; Chiang, Ying-Cheng; Chen, Yu-Li; Chen, Chi-An; Cheng, Wen-Fang

    2017-01-01

    We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease ( P Kruskal-Wallis test), serous and mixed histological types ( P = 0.003, Kruskal-Wallis test), malignant ascites ( P = 0.009, chi-square test), and history of other drug allergy ( P test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P test) and dose (6,816 vs. 3,844 mg, P test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.

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

    Science.gov (United States)

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

    2013-12-01

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

  17. The Natural History of Pneumonic Tularemia in Female Fischer 344 Rats after Inhalational Exposure to Aerosolized Francisella tularensis Subspecies tularensis Strain SCHU S4.

    Science.gov (United States)

    Hutt, Julie A; Lovchik, Julie A; Dekonenko, Alexander; Hahn, Andrew C; Wu, Terry H

    2017-02-01

    The inbred Fischer 344 rat is being evaluated for testing novel vaccines and therapeutics against pneumonic tularemia. Although primary pneumonic tularemia in humans typically occurs by inhalation of aerosolized bacteria, the rat model has relied on intratracheal inoculation of organisms because of safety and equipment issues. We now report the natural history of pneumonic tularemia in female Fischer 344 rats after nose-only inhalational exposure to lethal doses of aerosolized Francisella tularensis subspecies tularensis, strain SCHU S4. Our results are consistent with initial uptake of aerosolized SCHU S4 from the nasal cavity, lungs, and possibly the gastrointestinal tract. Bacteremia with hematogenous dissemination was first detected 2 days after exposure. Shortly thereafter, the infected rats exhibited fever, tachypnea, and hypertension that persisted for 24 to 36 hours and then rapidly decreased as animals succumbed to infection between days 5 and 8 after exposure. Tachycardia was observed briefly, but only after the core body temperature and blood pressure began to decrease as the animals were near death. Initial neutrophilic and histiocytic inflammation in affected tissues became progressively more fibrinous and necrotizing over time. At death, as many as 10 10 colony-forming units were found in the lungs, spleen, and liver. Death was attributed to sepsis and disseminated intravascular coagulation. Overall, the pathogenesis of pneumonic tularemia in the female F344 rat model appears to replicate the disease in humans. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Egan Joseph R

    2010-10-01

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

  1. Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion

    Directory of Open Access Journals (Sweden)

    L. D. Wang

    2016-01-01

    Full Text Available Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25 and Shangjuxu (ST37 acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25 and Shangjuxu (ST37 acupoints on spinal cord NR1, NR2B, and PKCε protein and mRNA expression in irritable bowel syndrome (IBS visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCε in the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCε in spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCε of spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Background. Traditionally, radiation therapy plans are optimized without consideration of chemotherapy. Here, we model the risk of radiation pneumonitis (RP) in the presence of a possible interaction between chemotherapy and radiation dose distribution. Material and methods. Three alternative......-radiation combinations could be an interesting indication for selecting patients for proton therapy. It is likely that the IMRT plans would perform better if the CERD was accounted for during optimization, but more clinical data is required to facilitate evidence-based plan optimization in the multi-modality setting....... treatment plans are compared in 18 non-small cell lung cancer patients previously treated with helical tomotherapy; the tomotherapy plan, an intensity modulated proton therapy plan (IMPT) and a three dimensional conformal radiotherapy (3D-CRT) plan. All plans are optimized without consideration...

  3. electro-hypersensitivity: survey among general practitioners, occupational physicians and hygienist from the Netherlands

    International Nuclear Information System (INIS)

    Bonnet-Belfais, Monique; Salines, Georges

    2017-01-01

    From October 2013 through January 2014, Dutch and Swiss researchers conducted a survey in the Netherlands on electro-hypersensitive (EHS) people among the health care providers likely to be consulted for primary care and prevention. (author)

  4. Hypersensitivity reactions to metallic implants-diagnostic algorithm and suggested patch test series for clinical use

    DEFF Research Database (Denmark)

    Schalock, Peter C; Menné, Torkil; Johansen, Jeanne D

    2011-01-01

    Cutaneous and systemic hypersensitivity reactions to implanted metals are challenging to evaluate and treat. Although they are uncommon, they do exist, and require appropriate and complete evaluation. This review summarizes the evidence regarding evaluation tools, especially patch and lymphocyte...... transformation tests, for hypersensitivity reactions to implanted metal devices. Patch test evaluation is the gold standard for metal hypersensitivity, although the results may be subjective. Regarding pre-implant testing, those patients with a reported history of metal dermatitis should be evaluated by patch...... testing. Those without a history of dermatitis should not be tested unless considerable concern exists. Regarding post-implant testing, a subset of patients with metal hypersensitivity may develop cutaneous or systemic reactions to implanted metals following implant. For symptomatic patients, a diagnostic...

  5. Nickel in nails, hair and plasma from nickel-hypersensitive women

    DEFF Research Database (Denmark)

    Gammelgaard, Bente; Veien, Niels

    1990-01-01

    The concentrations of nickel in finger-nails, toe-nails, hair and plasma from 71 nickel-hypersensitive women and 20 non-hypersensitive women were determined. Nickel concentrations in finger-nails were significantly higher than in toe-nails in both the nickel-hypersensitive group and the control...... group. Nickel-sensitive women had significantly higher levels of nickel in toe-nails, hair and plasma than had control subjects, whereas there was no significant difference in nickel concentration in finger-nails between the two groups. No correlation could be demonstrated between nickel levels in any...... combination of nails, hair and plasma in the nickel-hypersensitive or in the control group....

  6. Immunotoxicity of epicutaneously applied anticoagulant rodenticide warfarin: evaluation by contact hypersensitivity to DNCB in rats

    International Nuclear Information System (INIS)

    Kataranovski, Milena; Vlaski, Marija; Kataranovski, Dragan; Tosic, Natasa; Mandic-Radic, Slavka; Todorovic, Vera

    2003-01-01

    The immunotoxicity of epicutaneously administered anticoagulant rodenticide warfarin (WF) was examined in this work by using experimental contact hypersensitivity (CHS) reaction to hapten dinitrochlorobenzene (DNCB). WF (0.05 and 0.5 mg/kg) administration 24 h before the induction of CHS does not change expression of CHS evaluated by ear swelling assay. Regional draining lymph node response during sensitization phase was characterized by decreased cellularity but increased spontaneous and IL-2 stimulated proliferation of draining lymph node cells (DLC). No changes in IL-2 production and in numbers of CD25 + cells were noted and even decreased proliferative index (ratio of IL-2 stimulated to unstimulated DLC proliferation) was detected. Increase in granulocyte activity (MTT reduction and adhesion to plastic) was noted following application of WF solely with further increase following subsequent application of DNCB, when granulocyte activation (NBT reduction) was noted also. Access of WF into general circulation might be responsible for observed changes, what was supported by ex vivo changes in DLC and granulocyte functions assessed before initiation of sensitization and by in vitro effect of exogenous WF as well. Differential effects of WF on lymphocytes and granulocytes noted in this study highlight the need for simultaneous testing of both cell type activity what might constitute a more integrated approach in immunotoxicity studies

  7. Health-related quality of life in food hypersensitive schoolchildren and their families: parents' perceptions

    Directory of Open Access Journals (Sweden)

    Marklund Birgitta

    2006-08-01

    Full Text Available Abstract Background About 20% of schoolchildren and adolescents in Sweden suffer from perceived food hypersensitivity (e.g. allergy or intolerance. Our knowledge of how child food hypersensitivity affects parents HRQL and what aspects of the hypersensitivity condition relate to HRQL deterioration in the family is limited. Thus the aim of this study was to investigate the parent-reported HRQL in families with a schoolchild considered to be food hypersensitive. The allergy-associated parameters we operated with were number of offending food items, adverse food reactions, additional hypersensitivity, allergic diseases and additional family members with food hypersensitivity. These parameters, along with age and gender were assessed in relation to child, parent and family HRQL. Methods In May 2004, a postal questionnaire was distributed to parents of 220 schoolchildren with parent-reported food hypersensitivity (response rate 74%. Two questionnaires were used: CHQ-PF28 and a study-specific questionnaire including questions on allergy-associated parameters. In order to find factors that predict impact on HRQL, stepwise multiple linear regression analyses were carried out. Results An important predictor of low HRQL was allergic disease (i.e. asthma, eczema, rhino conjunctivitis in addition to food hypersensitivity. The higher the number of allergic diseases, the lower the physical HRQL for the child, the lower the parental HRQL and the more disruption in family activities. Male gender predicted lower physical HRQL than female gender. If the child had sibling(s with food hypersensitivity this predicted lower psychosocial HRQL for the child and lower parental HRQL. Food-induced gastro-intestinal symptoms predicted lower parental HRQL while food-induced breathing difficulties predicted higher psychosocial HRQL for the child and enhanced HRQL with regards to the family's ability to get along. Conclusion The variance in the child's physical HRQL was to a

  8. Yersinia pestis endowed with increased cytotoxicity is avirulent in a bubonic plague model and induces rapid protection against pneumonic plague.

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    Ayelet Zauberman

    Full Text Available An important virulence strategy evolved by bacterial pathogens to overcome host defenses is the modulation of host cell death. Previous observations have indicated that Yersinia pestis, the causative agent of plague disease, exhibits restricted capacity to induce cell death in macrophages due to ineffective translocation of the type III secretion effector YopJ, as opposed to the readily translocated YopP, the YopJ homologue of the enteropathogen Yersinia enterocolitica Oratio8. This led us to suggest that reduced cytotoxic potency may allow pathogen propagation within a shielded niche, leading to increased virulence. To test the relationship between cytotoxic potential and virulence, we replaced Y. pestis YopJ with YopP. The YopP-expressing Y. pestis strain exhibited high cytotoxic activity against macrophages in vitro. Following subcutaneous infection, this strain had reduced ability to colonize internal organs, was unable to induce septicemia and exhibited at least a 10(7-fold reduction in virulence. Yet, upon intravenous or intranasal infection, it was still as virulent as the wild-type strain. The subcutaneous administration of the cytotoxic Y. pestis strain appears to activate a rapid and potent systemic, CTL-independent, immunoprotective response, allowing the organism to overcome simultaneous coinfection with 10,000 LD(50 of virulent Y. pestis. Moreover, three days after subcutaneous administration of this strain, animals were also protected against septicemic or primary pneumonic plague. Our findings indicate that an inverse relationship exists between the cytotoxic potential of Y. pestis and its virulence following subcutaneous infection. This appears to be associated with the ability of the engineered cytotoxic Y. pestis strain to induce very rapid, effective and long-lasting protection against bubonic and pneumonic plague. These observations have novel implications for the development of vaccines/therapies against Y. pestis and shed

  9. Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress

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    Chen Zhao

    2018-01-01

    Full Text Available Background. Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1 is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs and the role of CHT1 in visceral hypersensitivity. Methods. Repetitive water avoidance stress (WAS was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD was determined, and the abdominal withdrawal reflex (AWR and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3, the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results. Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion. Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity.

  10. Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress

    Science.gov (United States)

    2018-01-01

    Background Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1) is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs) and the role of CHT1 in visceral hypersensitivity. Methods Repetitive water avoidance stress (WAS) was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD) was determined, and the abdominal withdrawal reflex (AWR) and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3), the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity. PMID:29849603

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

    OpenAIRE

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

    2012-01-01

    Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the di...

  12. Expression of antibacterial resistance at the site of a delayed hypersensitivity reaction.

    OpenAIRE

    Patel, P J

    1980-01-01

    The site of a delayed hypersensitivity reaction to tuberculin or bovine serum ablumin was shown to contain mechanisms that expressed increased antibacterial activity, as evidenced by restricted growth of a local inoculum of Listeria monocytogenes. As was the case with a delayed hypersensitivity reaction, the local generation of antibacterial activity was antigen specific and T-cell dependent. Antibacterial resistance was always expressed at the site of injection of specific antigen in sensiti...

  13. Food hypersensitivity in patients over 14 years of age suffering from atopic dermatitis

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    Jarmila Čelakovská

    2014-01-01

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

  14. Food hypersensitivity in patients over 14 years of age suffering from atopic dermatitis.

    Science.gov (United States)

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

    2014-05-01

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

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

    Science.gov (United States)

    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. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. The Relationship between Grandiose and Vulnerable (Hypersensitive Narcissism

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    Emanuel Jauk

    2017-09-01

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

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

    Science.gov (United States)

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

    2017-01-01

    Narcissistic grandiosity is characterized by overt expressions of feelings of superiority and entitlement, while narcissistic vulnerability reflects hypersensitivity and introversive self-absorbedness. Clinical evidence suggests that grandiosity is accompanied by vulnerable aspects, pointing to a common foundation. Subclinical personality research, however, views grandiose and vulnerable narcissism as independent traits. Grandiose narcissism displays substantial correlation with extraversion, while vulnerable narcissism correlates highly with introversion. We investigated if (1) controlling for intro-/extraversion might reveal a “common core” of grandiose and vulnerable narcissism, and if (2) the correlation between both aspects might be higher at higher levels of narcissism. Latent variable structural equation modeling and segmented regression analysis confirmed these hypotheses in a large non-clinical sample (N = 1,006). Interindividual differences in intro-/extraversion mask the common core of grandiose and vulnerable narcissism. The association between both aspects increases at high levels (upper 10%) of grandiose narcissism, which suggests a possible transition to clinically relevant (pathological) narcissism. PMID:28955288

  18. Exploring Some Aspects Associated with Dentine Hypersensitivity in Children

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    Caleb Shitsuka

    2015-01-01

    Full Text Available 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.

  19. A Case of Immediate Hypersensitivity Reaction to Maltitol

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    Ana Rodríguez Trabado

    2017-01-01

    Full Text Available Background. Maltitol is a sugar alcohol that is frequently used as a noncaloric sweetener, although it is also used as an excipient, a plasticizer in gelatin capsules, and an emollient. It has not been previously described as an agent involved in immediate hypersensitivity reactions. Methods. We report on an anaphylactoid reaction with pharyngeal occlusion suffered by a 60-year-old man after ingestion of a candy containing maltitol syrup. A prick-to-prick test was performed with the candy and maltitol powder. Other allergens were excluded as causative agents of the adverse reaction, although the patient refused to undergo an oral challenge test with the candy. A basophil activation test (BAT was performed with maltitol powder, and a dose-response curve was generated. The test was also performed in 3 healthy controls. Results. Both prick-to-prick tests were negative. The result of the BAT was positive at all the concentrations tested in the patient’s blood and negative in all the controls. Conclusions. The BAT can help to clarify the agents implicated in an adverse reaction and can reduce the risk involved in diagnosis. The BAT can also prove useful in the study of reactions caused by low-molecular-weight antigens, for which routine diagnostic tests are not feasible.

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

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    Romeo Umberto

    2012-01-01

    Full Text Available 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.

  1. Evaluation of the hypersensitivity potential of alternative butter flavorings

    Science.gov (United States)

    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. Presumed hydrochlorothiazide-associated immunologic-hypersensitivity-induced pericardial effusion

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    Michael J Chaskes

    2013-08-01

    Full Text Available A 50-year-old Caucasian female presented for a second opinion regarding a newly diagnosed pericardial effusion. Seven months previously, hydrochlorothiazide was introduced into her pharmacologic regimen to aid in the management of her hypertension. A routine echocardiogram indicated a large pericardial effusion with signs of early cardiac tamponade. The patient subsequently underwent successful pericardiocentesis with complete drainage of the pericardial effusion. The effusion was empirically attributed to a viral etiology. Repeat echocardiograms showed recurrence of the pericardial effusion. Prior to undergoing a second pericardiocentesis with pericardial biopsy, as her physicians recommended, the patient sought a second opinion. While obtaining the patient’s history, an allergy to sulfa was elicited. The possibility that the pericardial effusion may be secondary to an immunologic-hypersensitivity reaction was considered. It was recommended the patient discontinue the use of hydrochlorothiazide. Nine days following discontinuation of hydrochlorothiazide and without any other intervention, an echocardiogram was reported to show the size of the pericardial effusion had subsided substantially. Nine weeks following discontinuation, almost complete resolution of the pericardial effusion was reported. It is hypothesized that when treated with hydrochlorothiazide, the patient had an immune response leading to the pericardial effusion.

  3. Hypersensitive Reaction to Tattoos: A Growing Menace in Rural India.

    Science.gov (United States)

    Shashikumar, B M; Harish, M R; Shwetha, B; Kavya, M; Deepadarshan, K; Phani, H N

    2017-01-01

    Increased enthusiasm toward newer fashion trends among rural India along with the lack of government regulation has led to increased tattoo reactions. The objective of this study is to describe various clinical manifestations of hypersensitive reactions to tattoo ink reported at a tertiary care hospital in Mandya district. An observational study was carried out over a period of 1 year from June 2014 to May 2015 at Mandya Institute of Medical Sciences, Mandya. All the patients reporting with allergic reaction due to tattooing were included in the present study after obtaining informed consent. Transient acute inflammatory reaction, infections, and skin diseases localized on tattooed area were excluded from this study. A detailed history regarding the onset, duration and color used for tattooing were collected. Cutaneous examination and biopsy was to done to know the type of reaction. Fifty cutaneous allergic reactions were diagnosed among 39 patients. Mean age of subjects was 22 years and mean duration before the appearance of lesion was 7 months. Common colors associated with reactions were red (53.9%), black (33.3%), green (5.1%), and multicolor (7.7%). Itching was the predominant symptom. Skin lesions mainly consisted of lichenoid papules and plaques, eczematous lesions, and verrucous lesions. Lichenoid histopathology reaction was the most common tissue allergic reaction. Increasing popularity of tattooing among young people has predisposed to parallel increase in adverse reactions. Red pigment is most common cause of allergic reaction in the present study, and lichenoid reaction is the most common reaction.

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

    Science.gov (United States)

    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.

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

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    Andrew J. Mitchelson

    2015-01-01

    Full Text Available 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.

  6. Association of tinnitus and electromagnetic hypersensitivity: hints for a shared pathophysiology?

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    Michael Landgrebe

    Full Text Available BACKGROUND: Tinnitus is a frequent condition with high morbidity and impairment in quality of life. The pathophysiology is still incompletely understood. Electromagnetic fields are discussed to be involved in the multi-factorial pathogenesis of tinnitus, but data proofing this relationship are very limited. Potential health hazards of electromagnetic fields (EMF have been under discussion for long. Especially, individuals claiming themselves to be electromagnetic hypersensitive suffer from a variety of unspecific symptoms, which they attribute to EMF-exposure. The aim of the study was to elucidate the relationship between EMF-exposure, electromagnetic hypersensitivity and tinnitus using a case-control design. METHODOLOGY: Tinnitus occurrence and tinnitus severity were assessed by questionnaires in 89 electromagnetic hypersensitive patients and 107 controls matched for age-, gender, living surroundings and workplace. Using a logistic regression approach, potential risk factors for the development of tinnitus were evaluated. FINDINGS: Tinnitus was significantly more frequent in the electromagnetic hypersensitive group (50.72% vs. 17.5% whereas tinnitus duration and severity did not differ between groups. Electromagnetic hypersensitivity and tinnitus were independent risk factors for sleep disturbances. However, measures of individual EMF-exposure like e.g. cell phone use did not show any association with tinnitus. CONCLUSIONS: Our data indicate that tinnitus is associated with subjective electromagnetic hypersensitivity. An individual vulnerability probably due to an over activated cortical distress network seems to be responsible for, both, electromagnetic hypersensitivity and tinnitus. Hence, therapeutic efforts should focus on treatment strategies (e.g. cognitive behavioral therapy aiming at normalizing this dysfunctional distress network.

  7. The role for decorin in delayed-type hypersensitivity

    Science.gov (United States)

    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

  8. Hypersensitive reaction to tattoos: A growing menace in rural India

    Directory of Open Access Journals (Sweden)

    B M Shashikumar

    2017-01-01

    Full Text Available Background: Increased enthusiasm toward newer fashion trends among rural India along with the lack of government regulation has led to increased tattoo reactions. Objective: The objective of this study is to describe various clinical manifestations of hypersensitive reactions to tattoo ink reported at a tertiary care hospital in Mandya district. Materials and Methods: An observational study was carried out over a period of 1 year from June 2014 to May 2015 at Mandya Institute of Medical Sciences, Mandya. All the patients reporting with allergic reaction due to tattooing were included in the present study after obtaining informed consent. Transient acute inflammatory reaction, infections, and skin diseases localized on tattooed area were excluded from this study. A detailed history regarding the onset, duration and color used for tattooing were collected. Cutaneous examination and biopsy was to done to know the type of reaction. Results: Fifty cutaneous allergic reactions were diagnosed among 39 patients. Mean age of subjects was 22 years and mean duration before the appearance of lesion was 7 months. Common colors associated with reactions were red (53.9%, black (33.3%, green (5.1%, and multicolor (7.7%. Itching was the predominant symptom. Skin lesions mainly consisted of lichenoid papules and plaques, eczematous lesions, and verrucous lesions. Lichenoid histopathology reaction was the most common tissue allergic reaction. Conclusion: Increasing popularity of tattooing among young people has predisposed to parallel increase in adverse reactions. Red pigment is most common cause of allergic reaction in the present study, and lichenoid reaction is the most common reaction.

  9. Pomalidomide desensitization in a patient hypersensitive to immunomodulating agents

    Science.gov (United States)

    Seki, J.T.; Sakurai, N.; Lam, W.; Reece, D.E.

    2017-01-01

    Despite progressive treatments with tandem stem-cell transplantation, patients with incurable myeloma eventually succumb to relapsed or refractory disease if left untreated. Promising agents such as proteasome inhibitors and immunomodulating imide drugs (imids), including the newer-generation agent pomalidomide, in combination with lower-dose dexamethasone, have been shown to be effective and to significantly improve and prolong survival in pretreated patients. Although the incidence of pomalidomide hypersensitivity reaction (hsr) in this class of drugs is not as well known, we have documented cutaneous toxicity (grade 3 by the Common Terminology Criteria for Adverse Events, version 4) in 2 separate cases (not yet published). Because the imids are chemically, structurally, and pharmacologically similar, it is not unreasonable to consider possible cross-reactivity in pomalidomide recipients who developed hsr when receiving previous lines of imids. As a patient’s advocate, it is only prudent to provide a responsible, and yet practical, means to better address cross-sensitivity for patients. Intervention with the use of a rapid desensitization program (rdp) as a preventive measure should be introduced before initiating pomalidomide. Such a proactive measure for the patient’s safety will ensure a smooth transition into pomalidomide treatment. A hsr can be either related or non-related to immunoglobulin E. As imids become an essential treatment backbone for myeloma and other plasma-cell diseases, an increasing number of patients could experience skin and other life-threatening toxicities, resulting in unnecessary discontinuation of these life-prolonging agents. An extemporaneously prepared pomalidomide suspension developed at our centre enables patients to undergo rdp safely. Patients enjoy a good quality of life and clinical response after the rdp procedure. PMID:28874903

  10. Association of anticonvulsant hypersensitivity syndrome with Herpesvirus 6, 7.

    Science.gov (United States)

    Oskay, Tuğba; Karademir, Asli; Ertürk, Ozcan I

    2006-07-01

    Anticonvulsant hypersensitivity syndrome (AHS) is one of the most severe forms of drug eruption with potentially lethal, and multiorgan involvement. Recently, it has been suggested that Human Herpesvirus (HHV) infection has been involved in this syndrome, although the pathogenesis of this syndrome remains still unclear. The objective of this study was to determine the clinical characteristics of AHS and the possible role of viral infection as a co-factor. We prospectively analyzed clinical, laboratory and virological findings for 23 cases of AHS. A viral study including viral serology and a polymerase chain reaction (PCR) was performed. The most common anticonvulsant was carbamazepine (12) followed by phenytoin (6), phenobarbital (4) and gabapentin (1). All patients met fulfill the clinical criteria of AHS. Even though internal organ involvement such as liver (52%), kidney (34%), and lung (13%) has been observed, involvement of heart, lung, thyroid, muscle, pancreas, spleen, and brain was less frequent. We also noted two patients who died due to multiorgan failure. No association with viral infection including HSV, VZV, HHV-8, CMV, EBV, measles, rubella and parvovirus B19 was detected in the current series. Increased serum anti-HHV-6 IgG and HHV-7 titers and presence of HHV-6 and -7 DNA in serum, revealed by PCR analysis, suggested reactivation of HHV-6. In contrast to the control groups, DNA for HHV-6 was detected in serum in 5 out of the 23 patients while HHV-7 was seen in two patients. We found an evidence to link reactivation of HHV-6 or HHV-7 in the development of only carbamazepine-induced AHS. We propose that some cases of AHS are accompanied by reactivation of not only HHV-6 but also HHV-7. HHV infection may contribute to the severity, prolongation, or relapse of AHS and may possibly have fatal consequences in some susceptible individuals receiving the anticonvulsants.

  11. Gemcitabine and paclitaxel associated pneumonitis in non-small cell lung cancer: report of a phase I/II dose-escalating study.

    Science.gov (United States)

    Thomas, A L; Cox, G; Sharma, R A; Steward, W P; Shields, F; Jeyapalan, K; Muller, S; O'Byrne, K J

    2000-12-01

    The aim of this phase I/II dose escalating study was to establish the maximum tolerated dose (MTD) of gemcitabine and paclitaxel given in combination in non-small cell lung cancer (NSCLC). 12 patients with stage IIIB and IV NSCLC received paclitaxel administered intravenously over 1 h followed by gemcitabine given over 30 min on days 1, 8 and 15 every 28 days. Pneumonitis was the principal side-effect observed with 4 patients affected. Of these, 1 experienced grade 3 toxicity after one cycle of treatment and the others had grade 2 toxicity. All 4 cases responded to prednisolone. No other significant toxicities were observed. Of the 8 evaluable patients, 3 had a partial response and 2 had minor responses. The study was discontinued due to this dose-limiting toxicity. The combination of paclitaxel and gemcitabine shows promising antitumour activity in NSCLC, however, this treatment schedule may predispose to pneumonitis.

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

    Directory of Open Access Journals (Sweden)

    Chang Joe Y

    2012-09-01

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

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier GmbH. All rights reserved.

  14. Role of insular cortex in visceral hypersensitivity model in rats subjected to chronic stress.

    Science.gov (United States)

    Yi, LiSha; Sun, HuiHui; Ge, Chao; Chen, Ying; Peng, HaiXia; Jiang, YuanXi; Wu, Ping; Tang, YinHan; Meng, QingWei; Xu, ShuChang

    2014-12-30

    Abnormal processing of visceral sensation at the level of the central nervous system has been proven to be important in the pathophysiologic mechanisms of stress related functional gastrointestinal disorders. However, the specific mechanism is still not clear. The insular cortex (IC) was considered as one important visceral sensory area. Moreover, the IC has been shown to be involved in various neuropsychiatric diseases such as panic disorders and post-traumatic stress disorder. However, whether the IC is important in psychological stress related visceral hypersensitivity has not been studied yet. In our study, through destruction of the bilateral IC, we explored whether the IC played a critical role in the formation of visceral hypersensitivity induced by chronic stress on rats. Chronic partial restraint stress was used to establish viscerally hypersensitive rat model. Bilateral IC lesions were generated by N-methyl-D-day (door) aspartate. After a recovery period of 7 days, 14-day consecutive restraint stress was performed. The visceromotor response to colorectal distension was monitored by recording electromyogram to measure rats׳ visceral sensitivity. We found that bilateral insular cortex lesion could markedly inhibit the formation of visceral hypersensitivity induced by chronic stress. The insular cortex plays a critical role in the pathophysiology of stress-related visceral hypersensitivity.

  15. Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Nóra Kutszegi

    Full Text Available L-asparaginase (ASP is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL. However, hypersensitivity reactions (HSRs to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin-Frankfurt-Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01-0.26; p = 4.70E-04, while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176 were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09-0.53; p = 8.48E-04 and OR = 3.02 (1.36-6.73; p = 6.76E-03, respectively. Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-02-15

    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.

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

    International Nuclear Information System (INIS)

    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

  18. Sensory hypersensitivity predicts enhanced attention capture by faces in the early development of ASD

    Directory of Open Access Journals (Sweden)

    E.J.H Jones

    2018-01-01

    Full Text Available Sensory sensitivity is prevalent among young children with ASD, but its relation to social communication impairment is unclear. Recently, increased sensory hypersensitivity has been linked to greater activity of the neural salience network (Green et al., 2016. Increased neural sensitivity to stimuli, especially social stimuli, could provide greater opportunity for social learning and improved outcomes. Consistent with this framework, in Experiment 1 we found that parent report of greater sensory hypersensitivity at 2 years in toddlers with ASD (N = 27 was predictive of increased neural responsiveness to social stimuli (larger amplitude event-related potential/ERP responses to faces at P1, P400 and Nc at 4 years, and this in turn was related to parent report of increased social approach at 4 years. In Experiment 2, parent report of increased perceptual sensitivity at 6 months in infants at low and high familial risk for ASD (N = 35 predicted larger ERP P1 amplitude to faces at 18 months. Increased sensory hypersensitivity in early development thus predicted greater attention capture by faces in later development, and this related to more optimal social behavioral development. Sensory hypersensitivity may index a child's ability to benefit from supportive environments during development. Early sensory symptoms may not always be developmentally problematic for individuals with ASD. Keywords: Autism, Sensory hypersensitivity, Social attention, Salience network, Infant, EEG

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

    Science.gov (United States)

    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.

  20. Carboplatin Hypersensitivity Reactions in Pediatric Low Grade Glioma Are Protocol Specific and Desensitization Shows Poor Efficacy.

    Science.gov (United States)

    Dodgshun, Andrew J; Hansford, Jordan R; Cole, Theresa; Choo, Sharon; Sullivan, Michael J

    2016-01-01

    The use of carboplatin for the treatment of pediatric low grade gliomas (PLGG) is often limited by the development of carboplatin hypersensitivity. Reported rates of carboplatin hypersensitivity reactions vary between 6% and 32% in these patients. Here we report the frequency of carboplatin hypersensitivity reactions depending on the treatment regimen used, and outcomes of carboplatin desensitization. The records of all patients in a single institution who were treated with carboplatin for PLGG were accessed and all patients receiving more than one dose of carboplatin are reported. Thirty four patients with PLGG were treated with carboplatin according to one of the two different regimens. Carboplatin hypersensitivity was documented in 47% of patients, but the frequency differed by treatment protocol. Those patients treated with 4-weekly single agent carboplatin had carboplatin allergy in 8% of cases whereas 68% of those treated with combined carboplatin and vincristine (every three weeks, according to the SIOP 2004 low grade glioma protocol) had carboplatin reactions (OR 23.6, P Desensitization was only successful in two out of 10 patients in whom it was attempted. Hypersensitivity reactions to carboplatin are more common in this cohort than previously reported and rates are protocol-dependent. Desensitization showed limited effectiveness in this cohort. © 2015 Wiley Periodicals, Inc.

  1. Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Trials.

    Science.gov (United States)

    Khunger, Monica; Rakshit, Sagar; Pasupuleti, Vinay; Hernandez, Adrian V; Mazzone, Peter; Stevenson, James; Pennell, Nathan A; Velcheti, Vamsidhar

    2017-08-01

    Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune-mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use. MEDLINE, Embase, and Scopus databases were searched up to November 2016. Rates of pneumonitis of any grade and grade ≥ 3 from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab as single agents in NSCLC were collected. The incidence of pneumonitis across trials was calculated using DerSimonian-Laird random effects models. We compared incidences between PD-1 and PD-L1 inhibitors and between treatment naive and previously treated patients. Nineteen trials (12 with PD-1 inhibitors [n = 3,232] and 7 with PD-L1 inhibitors [n = 1,806]) were identified. PD-1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis compared with PD-L1 inhibitors (3.6%; 95% CI, 2.4%-4.9% vs 1.3%; 95% CI, 0.8%-1.9%, respectively; P = .001). PD-1 inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis (1.1%; 95% CI, 0.6%-1.7% vs 0.4%; 95% CI, 0%-0.8%; P = .02). Treatment naive patients had higher incidence of grade 1 through 4 pneumonitis compared with previously treated patients (4.3%; 95% CI, 2.4%-6.3% vs 2.8%; 95% CI, 1.7%- 4%; P = .03). There was a higher incidence of pneumonitis with use of PD-1 inhibitors compared with PD-L1 inhibitors. Higher rate of pneumonitis was more common in treatment naive patients. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  2. pDHS-SVM: A prediction method for plant DNase I hypersensitive sites based on support vector machine.

    Science.gov (United States)

    Zhang, Shanxin; Zhou, Zhiping; Chen, Xinmeng; Hu, Yong; Yang, Lindong

    2017-08-07

    DNase I hypersensitive sites (DHSs) are accessible chromatin regions hypersensitive to cleavages by DNase I endonucleases. DHSs are indicative of cis-regulatory DNA elements (CREs), all of which play important roles in global gene expression regulation. It is helpful for discovering CREs by recognition of DHSs in genome. To accelerate the investigation, it is an important complement to develop cost-effective computational methods to identify DHSs. However, there is a lack of tools used for identifying DHSs in plant genome. Here we presented pDHS-SVM, a computational predictor to identify plant DHSs. To integrate the global sequence-order information and local DNA properties, reverse complement kmer and dinucleotide-based auto covariance of DNA sequences were applied to construct the feature space. In this work, fifteen physical-chemical properties of dinucleotides were used and Support Vector Machine (SVM) was employed. To further improve the performance of the predictor and extract an optimized subset of nucleotide physical-chemical properties positive for the DHSs, a heuristic nucleotide physical-chemical property selection algorithm was introduced. With the optimized subset of properties, experimental results of Arabidopsis thaliana and rice (Oryza sativa) showed that pDHS-SVM could achieve accuracies up to 87.00%, and 85.79%, respectively. The results indicated the effectiveness of proposed method for predicting DHSs. Furthermore, pDHS-SVM could provide a helpful complement for predicting CREs in plant genome. Our implementation of the novel proposed method pDHS-SVM is freely available as source code, at https://github.com/shanxinzhang/pDHS-SVM. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Electromagnetic hypersensitivity (EHS) in the media - a qualitative content analysis of Norwegian newspapers.

    Science.gov (United States)

    Huiberts, Ashild; Hjørnevik, Mari; Mykletun, Arnstein; Skogen, Jens C

    2013-01-01

    Electromagnetic hypersensitivity (EHS) is a condition characterized by experiencing symptoms after perceived exposure to weak electromagnetic fields (EMFs). There is substantial debate concerning the aetiology of EHS, but experimental data indicate no association between EHS and actual presence of EMFs. Newspapers play a key role in shaping peoples' understanding of health-related issues. The aim of this study was to describe the content of newspaper articles concerning aetiology and treatment of EHS. Qualitative content analysis of newspaper articles. Norwegian newspaper articles were identified using a comprehensive electronic media archive. Norwegian newspaper articles published between 1 February 2006 and 11 August 2010. Statements coded according to source of information, whether it was pro or con scientific evidence on EHS aetiology, and type of intervention presented as treatment option for EHS. Of the statements concerning EHS aetiology (n = 196), 35% (n = 69) were categorized as pro evidence, 65% (n = 127) as con evidence. Of the statements about EHS interventions assessed, 78% (n = 99) were categorized as 'radiance reduction', 4% (n = 5) as 'complementary medicine', and 18% (n = 23) as 'other'. Cognitive behavioural therapy (CBT) and psychotropic drugs were never presented as possible treatment options for EHS. The newspaper media discourse of EHS aetiology and recommended treatment interventions is much in conflict with the current evidence in the field. The majority of statements concerning aetiology convey that EHS is related to the presence of weak EMFs, and radiance reduction as the most frequently conveyed measure to reduce EHS-related symptoms.

  4. Evidentiation of Paramyosin (Sm-97 as a Modulating Antigen on Granulomatous Hypersensitivity to Schistosoma mansoni Eggs

    Directory of Open Access Journals (Sweden)

    Hirsch Cristine

    1997-01-01

    Full Text Available A Schistosoma mansoni adult worm anionic fraction (PIII has previously been shown to protect mice against challenge infection and to reduce pulmonary and hepatic granulomatous hypersensitivity. Serum from PIII-immunized rabbit was used to screen a lgt11 cDNA library from S. mansoni adult worm in order to identify antigens capable of modulating granulomatous hypersensitivity. We obtained four clones with 400 (Sm-III.11, 900 (Sm-III.16, 1100 (Sm-III.10 and 1300 (Sm-III.12 bp of length. All clone-specific antibodies were able to recognize most of the PIII components. The sequence analysis showed that these clones presented high homology with S. mansoni paramyosin (Sm-97. These findings ascribe a new function to this antigen with an important role in modulation of granulomatous hypersensitivity to S. mansoni eggs

  5. Hypersensitivity reactions to metallic implants-diagnostic algorithm and suggested patch test series for clinical use

    DEFF Research Database (Denmark)

    Schalock, Peter C; Menné, Torkil; Johansen, Jeanne D

    2011-01-01

    algorithm to guide the selection of screening allergen series for patch testing is provided. At a minimum, an extended baseline screening series and metal screening is necessary. Static and dynamic orthopaedic implants, intravascular stent devices, implanted defibrillators and dental and gynaecological......Cutaneous and systemic hypersensitivity reactions to implanted metals are challenging to evaluate and treat. Although they are uncommon, they do exist, and require appropriate and complete evaluation. This review summarizes the evidence regarding evaluation tools, especially patch and lymphocyte...... transformation tests, for hypersensitivity reactions to implanted metal devices. Patch test evaluation is the gold standard for metal hypersensitivity, although the results may be subjective. Regarding pre-implant testing, those patients with a reported history of metal dermatitis should be evaluated by patch...

  6. Leukemoid reaction secondary to hypersensitivity syndrome to phenobarbital: a case report.

    Science.gov (United States)

    Zeng, Qinghai; Wu, Yuanqiang; Zhan, Yi; Tang, Ling; Zhou, Yangmei; Yin, Jun; Fan, Fan; Zhang, Guiying; Lu, Qianjin; Xiao, Rong

    2013-01-01

    The most important adverse effects of phenobarbital, an anticonvulsant drug, are behavior and cognitive alterations. Hypersensitivity syndrome caused by phenobarbital presenting with a leukemoid reaction is a rare side effect, which is rarely ever reported and needs to be known. We report on a 27-year-old Chinese woman who experienced hypersensitivity syndrome three weeks after the initiation of phenobarbital. The patient developed fever, skin rash, face swelling, lymphadenopathy, myalgia, hepatitis, eosinophilia, atypical lymphocytes and leukocytosis. Along with the pathological progress of the disease, the patient noticed a gradual exacerbation of her symptoms. And the highest leukocyte count was up to 127.2 x 10(9)/L. After discontinuing of phenobarbital and administration of methylprednisolone combined with the intravenous immunoglobulin shock therapy, all initial symptoms improved and the leukocyte count normalized. This case is reported because of its rarity of the leukemoid reaction secondary to hypersensitivity syndrome to phenobarbital.

  7. Dose-volume histogram analysis as predictor of radiation pneumonitis in primary lung cancer patients treated with radiotherapy

    International Nuclear Information System (INIS)

    Fay, Michael; Tan, Alex; Fisher, Richard; Mac Manus, Michael; Wirth, Andrew; Ball, David

    2005-01-01

    Purpose: To determine the relationship between various parameters derived from lung dose-volume histogram analysis and the risk of symptomatic radiation pneumonitis (RP) in patients undergoing radical radiotherapy for primary lung cancer. Methods and Materials: The records of 156 patients with lung cancer who had been treated with radical radiotherapy (≥45 Gy) and for whom dose-volume histogram data were available were reviewed. The incidence of symptomatic RP was correlated with a variety of parameters derived from the dose-volume histogram data, including the volume of lung receiving 10 Gy (V 10 ) through 50 Gy (V 50 ) and the mean lung dose (MLD). Results: The rate of RP at 6 months was 15% (95% confidence interval 9-22%). On univariate analysis, only V 30 (p = 0.036) and MLD (p = 0.043) were statistically significantly related to RP. V 30 correlated highly positively with MLD (r = 0.96, p 30 and MLD can be used to predict the risk of RP in lung cancer patients undergoing radical radiotherapy

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    Purpose: To determine the incidence of and risk factors for radiation pneumonitis (RP) after stereotactic ablative radiation therapy (SABR) to the lung in patients who had previously undergone conventional thoracic radiation therapy. Methods and Materials: Seventy-two patients who had previously received conventionally fractionated radiation therapy to the thorax were treated with SABR (50 Gy in 4 fractions) for recurrent disease or secondary parenchymal lung cancer (T 10 and mean lung dose (MLD) of the previous plan and the V 10 -V 40 and MLD of the composite plan were also related to RP. Multivariate analysis revealed that ECOG PS scores of 2-3 before SABR (P=.009), FEV1 ≤65% before SABR (P=.012), V 20 ≥30% of the composite plan (P=.021), and an initial PTV in the bilateral mediastinum (P=.025) were all associated with RP. Conclusions: We found that severe RP was relatively common, occurring in 20.8% of patients, and could be predicted by an ECOG PS score of 2-3, an FEV1 ≤65%, a previous PTV spanning the bilateral mediastinum, and V 20 ≥30% on composite (previous RT+SABR) plans. Prospective studies are needed to validate these predictors and the scoring system on which they are based.

  9. Correlation of the acute oxidative stress markers with radiation induced late lung disease response of pneumonitis and/or fibrosis

    International Nuclear Information System (INIS)

    Kunwar, Amit

    2016-01-01

    Biomarkers which predict for the occurrence of radiation-induced lung responses of pneumonitis and/or fibrosis are largely unknown. Herein, we investigated whether markers of oxidative stress and intracellular antioxidants, measured within days of radiation exposure, correlated with the lung tissue injury response occurring weeks later. Inbred strains of mice (KK/HIJ, C57BL/6J, 129S1/SvImJ, C3H/HeJ, A/J, AKR/J, CBA/J, NZW/LacJ) known to differ in their susceptibility to radiation induced pulmonary fibrosis, and to vary in time to onset of respiratory distress post thoracic irradiation (from 10-23 weeks) were studied. Mice were unirradiated (controls) or received whole thorax irradiation (18 Gy) and were euthanized at 6h, 1d, 7d, 8w and upon presentation of respiratory distress. Pulmonary levels of antioxidants superoxide dismutase, catalase, glutathione peroxidase (GPx) and glutathione, and of oxidative damage (reactive oxygen species (ROS), 8-hydroxydeoxyguanosine (8-OHdG) and numbers of γH2AX foci), were assessed

  10. Defective DNA cross-link removal in Chinese hamster cell mutants hypersensitive to bifunctional alkylating agents

    International Nuclear Information System (INIS)

    Hoy, C.A.; Thompson, L.H.; Mooney, C.L.; Salazar, E.P.

    1985-01-01

    DNA repair-deficient mutants from five genetic complementation groups isolated previously from Chinese hamster cells were assayed for survival after exposure to the bifunctional alkylating agents mitomycin C or diepoxybutane. Groups 1, 3, and 5 exhibited 1.6- to 3-fold hypersensitivity compared to the wild-type cells, whereas Groups 2 and 4 exhibited extraordinary hypersensitivity. Mutants from Groups 1 and 2 were exposed to 22 other bifunctional alkylating agents in a rapid assay that compared cytotoxicity of the mutants to the wild-type parental strain, AA8. With all but two of the compounds, the Group 2 mutant (UV4) was 15- to 60-fold more sensitive than AA8 or the Group 1 mutant (UV5). UV4 showed only 6-fold hypersensitivity to quinacrine mustard. Alkaline elution measurements showed that this compound produced few DNA interstrand cross-links but numerous strand breaks. Therefore, the extreme hypersensitivity of mutants from Groups 2 and 4 appeared specific for compounds the main cytotoxic lesions of which were DNA cross-links. Mutant UV5 was only 1- to 4-fold hypersensitive to all the compounds. Although the initial number of cross-links was similar for the three cell lines, the efficiency of removal of cross-links was lowest in UV4 and intermediate in UV5. These results suggest that the different levels of sensitivity are specifically related to different efficiencies of DNA cross-link removal. The phenotype of hypersensitivity to both UV radiation and cross-link damage exhibited by the mutants in Groups 2 and 4 appears to differ from those of the known human DNA repair syndromes

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

    Directory of Open Access Journals (Sweden)

    Chunhua Zhang

    Full Text Available 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

  12. Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats

    Directory of Open Access Journals (Sweden)

    Alison Diesel

    2017-05-01

    Full Text Available Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly “feline atopic syndrome” when compared to dogs or people. This article aims to review what is currently known in regards to allergic skin disease in the feline patient, with focus on non-flea, non-food hypersensitivity dermatitis.

  13. Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats.

    Science.gov (United States)

    Diesel, Alison

    2017-05-09

    Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly "feline atopic syndrome" when compared to dogs or people. This article aims to review what is currently known in regards to allergic skin disease in the feline patient, with focus on non-flea, non-food hypersensitivity dermatitis.

  14. Cloning and expression of candidate allergens from Culicoides obsoletus for diagnosis of insect bite hypersensitivity in horses

    NARCIS (Netherlands)

    Meide, van der N.M.A.; Roders, N.; Sloet van Oldruitenborgh-Oosterbaan, M.M.; Schaap, P.J.; Oers, van M.M.; Leibold, W.; Savelkoul, H.F.J.; Tijhaar, E.

    2013-01-01

    Insect bite hypersensitivity (IBH) is an IgE-mediated (Type I) hypersensitivity reaction induced by allergens from biting midges of the Culicoides spp. The aim of the present study was to identify, clone and express recombinant allergens from C. obsoletus, the main species found feeding on horses in

  15. Drug hypersensitivity in children: report from the pediatric task force of the EAACI Drug Allergy Interest Group

    NARCIS (Netherlands)

    Gomes, E. R.; Brockow, K.; Kuyucu, S.; Saretta, F.; Mori, F.; Blanca-Lopez, N.; Ott, H.; Atanaskovic-Markovic, M.; Kidon, M.; Caubet, J.-C.; Terreehorst, I.

    2016-01-01

    When questioned, about 10% of the parents report suspected hypersensitivity to at least one drug in their children. However, only a few of these reactions can be confirmed as allergic after a diagnostic workup. There is still a lack of knowledge on drug hypersensitivity (DH) epidemiology, clinical

  16. Natural history of perceived food hypersensitivity and IgE sensitisation to food allergens in a cohort of adults.

    Science.gov (United States)

    Patelis, Antonios; Gunnbjörnsdottir, Maria; Borres, Magnus P; Burney, Peter; Gislason, Thorarinn; Torén, Kjell; Forsberg, Bertil; Alving, Kjell; Malinovschi, Andrei; Janson, Christer

    2014-01-01

    No longitudinal studies exist on the natural history of food hypersensitivity and IgE sensitisation to food allergens in adults. To examine the natural history of food hypersensitivity, the natural history of IgE sensitisation to food allergens and to investigate the risk factors for new onset food hypersensitivity. Food hypersensitivity was questionnaire-assessed in 2307 individuals (aged 20-45 years) from Iceland and Sweden during the European Community Respiratory Health Survey both at baseline and follow-up 9 years later. IgE food and aeroallergen sensitisation were assessed in a subgroup of these individuals (n = 807). Values of 0.35 kU/L and above were regarded as positive sensitisation. Food hypersensitivity was reported by 21% of the subjects and this proportion remained unchanged at follow-up (p = 0.58). Fruits, nuts and vegetables were the three most common causes of food hypersensitivity, with a similar prevalence at baseline and follow-up. The prevalence IgE sensitisation to food allergens decreased in general by 56% (pfood hypersensitivity. The prevalence of food hypersensitivity remained unchanged while the prevalence of IgE sensitisation to food allergens decreased in adults over a 9-year follow-up period. The decrease in prevalence of IgE sensitisation to food allergens was considerably larger than the change in prevalence of IgE sensitisation to aeroallergens.

  17. Hypersensitivity reaction with intravenous GnRH after pulsatile subcutaneous GnRH treatment in male hypogonadotrophic hypogonadism.

    OpenAIRE

    Popović, V.; Milosević, Z.; Djukanović, R.; Micić, D.; Nesović, M.; Manojlović, D.; Djordjević, P.; Mićić, J.

    1988-01-01

    Chronic pulsatile subcutaneous administration of low doses of gonadotrophin releasing hormone (GnRH) is an effective therapy for men with hypogonadotrophic hypogonadism. Hypersensitivity reactions to GnRH are rare. We wish to report hypersensitivity reactions with intravenous GnRH after low dose subcutaneous pulsatile GnRH treatment in two men with hypogonadotrophic hypogonadism due to suprasellar disease.

  18. Evidence of isolate-specificity in non-hypersensitive resistance in spring wheat (Triticum aestivum) to wheat leaf rust

    NARCIS (Netherlands)

    Qamar, Maqsood; Niks, R.E.

    2007-01-01

    Isolate-specific aspect of non-hypersensitive resistance in wheat to wheat leaf rust was studied at seedling stage in the green house. Isolate-specific response of non-hypersensitive resistance was assessed from latency period (LP) and infection frequency (IF) of two single-pustule isolates of

  19. Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain

    OpenAIRE

    Da-Lu Liu; Na Lu; Wen-Juan Han; Rong-Gui Chen; Rui Cong; Rou-Gang Xie; Yu-Fei Zhang; Wei-Wei Kong; San-Jue Hu; Ceng Luo

    2015-01-01

    Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron?s ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensit...

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

    International Nuclear Information System (INIS)

    Wang Shulian; Liao Zhongxing; Wei Xiong; Liu, Helen H.; Tucker, Susan L.; Hu Chaosu; Mohan, Rodhe; Cox, James D.; Komaki, Ritsuko

    2006-01-01

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

  1. System-Wide Hypersensitive Response-Associated Transcriptome and Metabolome Reprogramming in Tomato

    NARCIS (Netherlands)

    Etalo, D.W.; Stulemeijer, I.J.E.; Esse, van H.P.; Vos, de R.C.H.; Bouwmeester, H.J.; Joosten, M.H.A.J.

    2013-01-01

    The hypersensitive response (HR) is considered to be the hallmark of the resistance response of plants to pathogens. To study HR-associated transcriptome and metabolome reprogramming in tomato (Solanum lycopersicum), we used plants that express both a resistance gene to Cladosporium fulvum and the

  2. High cytokinin levels induce a hypersensitive-like response in tobacco

    Czech Academy of Sciences Publication Activity Database

    Novák, J.; Pavlů, J.; Novák, Ondřej; Nožková-Hlaváčková, V.; Špundová, M.; Hlavinka, J.; Koukalová, Š.; Skalák, J.; Černý, M.; Brzobohatý, B.

    2013-01-01

    Roč. 112, č. 1 (2013), s. 41-55 ISSN 0305-7364 R&D Projects: GA MŠk 1M06030; GA MŠk LK21306 Institutional support: RVO:61389030 Keywords : Cytokinin * hypersensitive response * hydrogen peroxide Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.295, year: 2013

  3. Kodak film type SO-394-4-1 mottling and hypersensitization test

    Science.gov (United States)

    Weinstein, M. S.

    1972-01-01

    A number of tests were conducted to show the effects of various environmental conditions in terms of mottling and hypersensitization on Kodak Film type SO-394-4-1. The first two weeks of environmental testing is described, along with the test plan and matrix.

  4. Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation

    NARCIS (Netherlands)

    I.M. van der Sluis (Inge); L.M. Vrooman (Lynda M.); R. Pieters (Rob); A. Baruchel (André); G. Escherich (Gabriele); N. Goulden (Nicholas); V. Mondelaers (Veerle); J.S. de Toledo (Jose Sanchez); C. Rizzari (Carmelo); L.B. Silverman (Lewis); J.A. Whitlock (James A.)

    2016-01-01

    textabstractL-asparaginase is an integral component of therapy for acute lymphoblastic leukemia. However, asparaginase-related complications, including the development of hypersensitivity reactions, can limit its use in individual patients. Of considerable concern in the setting of clinical allergy

  5. Should patients with risk factors be tested for hypersensitivity to contrast media: a prospective study.

    Science.gov (United States)

    Tepetam, Fatma Merve; Çiftaslan, Nezihe; Oruç, Özlem; Duman, Dildar; Ağca, Meltem; Bulut, İsmet; Çolakoğlu, Bahattin

    2016-08-01

    Previous hypersensitivity reactions to contrast media (CM), atopy, atopic disease, drug allergy, and age (20-29 or >55) are risk factors for CM hypersensitivity reactions. Our aim was to evaluate whether these risk factors should prompt skin testing for diagnosing CM allergy. The study was conducted among patients referred for allergy testing with CM. Skin tests were performed with non ionic or gadolinium CM, recommended by a radiologist. After completion of tests patients were telephonically queried on their symptoms of reactions. 151 risk patients (53 men, 98 women; mean age 55.2) were included in the study. Only 13 (9 %) had a history of hypersensitivity reaction to CM. Compared with the other patients, atopy was significantly more common in patients with a history of CM hypersensitivity reactions. Female gender and mean age were also higher, but not significant. All of the tests with CMs were negative. Only one patient reported urticaria within 1-2 min after administration of CM (telephonically). Atopy can increase the risk of CM allergy. However, skin tests with CMs may be inefficient, unnecessary, and time-consuming, except in cases with a history of CM allergy. Premedication protocols appear to be beneficial in patients with a history of CM allergy and cannot be recommended for patients with well-controlled asthma, rhinitis, atopic dermatitis or history of drug allergy.

  6. Identification of factors associated with the development of insect bite hypersensitivity in horses in the Netherlands

    NARCIS (Netherlands)

    Boom, van den R.; Ducro, B.J.; Sloet van Oldruitenborgh-Oosterbaan, M.M.

    2008-01-01

    An Internet-based questionnaire among horse owners was carried out to identify factors affecting the incidence of insect bite hypersensitivity (IBHI) among horses in the Netherlands. Information was obtained for 794 horses of various breeds, but the breed distribution was not representative for the

  7. Effect of Rap1 binding on DNA distortion and potassium permanganate hypersensitivity.

    Science.gov (United States)

    Le Bihan, Yann-Vaï; Matot, Béatrice; Pietrement, Olivier; Giraud-Panis, Marie-Josèphe; Gasparini, Sylvaine; Le Cam, Eric; Gilson, Eric; Sclavi, Bianca; Miron, Simona; Le Du, Marie-Hélène

    2013-03-01

    Repressor activator protein 1 (Rap1) is an essential factor involved in transcription and telomere stability in the budding yeast Saccharomyces cerevisiae. Its interaction with DNA causes hypersensitivity to potassium permanganate, suggesting local DNA melting and/or distortion. In this study, various Rap1-DNA crystal forms were obtained using specifically designed crystal screens. Analysis of the DNA conformation showed that its distortion was not sufficient to explain the permanganate reactivity. However, anomalous data collected at the Mn edge using a Rap1-DNA crystal soaked in potassium permanganate solution indicated that the DNA conformation in the crystal was compatible with interaction with permanganate ions. Sequence-conservation analysis revealed that double-Myb-containing Rap1 proteins all carry a fully conserved Arg580 at a position that may favour interaction with permanganate ions, although it is not involved in the hypersensitive cytosine distortion. Permanganate reactivity assays with wild-type Rap1 and the Rap1[R580A] mutant demonstrated that Arg580 is essential for hypersensitivity. AFM experiments showed that wild-type Rap1 and the Rap1[R580A] mutant interact with DNA over 16 successive binding sites, leading to local DNA stiffening but not to accumulation of the observed local distortion. Therefore, Rap1 may cause permanganate hypersensitivity of DNA by forming a pocket between the reactive cytosine and Arg580, driving the permanganate ion towards the C5-C6 bond of the cytosine.

  8. Culicoides obsoletus extract relevant for diagnostics of insect bite hypersensitivity in horses

    NARCIS (Netherlands)

    Meide, van der N.M.A.; Meulenbroeks, C.; Altena, van S.E.C.; Schurink, A.; Ducro, B.J.; Wagner, B.; Leibold, W.; Rohwer, J.; Jacobs, F.; Sloet van Oldruitenborgh-Oosterbaan, M.M.; Savelkoul, H.F.J.; Tijhaar, E.

    2012-01-01

    Insect bite hypersensitivity (IBH) is an allergic dermatitis in horses caused by the bites of Culicoides species. The aim of the present study was to evaluate the applicability of whole body extracts of C. obsoletus (the main species found feeding on horses in the Netherlands), C. nubeculosus

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

    NARCIS (Netherlands)

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

    2013-01-01

    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 IBM season.

  10. Prevalence of self-reported food hypersensitivity among school children in The Netherlands

    NARCIS (Netherlands)

    Brugman, E.; Meulmeester, J.F.; Spee-Wekke, A. van der; Beuker, R.J.; Radder, J.J.; Verloove-Vanhorick, S.P.

    1998-01-01

    Objectives: To provide national figures on the prevalence of self-reported food hypersensitivity (S-FH), and the association with socio-demographic variables and some health indicators in schoolchildren in The Netherlands. Design: As part of the Child Health Monitoring System, data were collected

  11. Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions.

    LENUS (Irish Health Repository)

    McCormack, Mark

    2012-03-01

    An association between carbamazepine-induced hypersensitivity and HLA-A*3101 has been reported in populations of both European and Asian descent. We aimed to investigate HLA-A*3101 and other common variants across the genome as markers for cutaneous adverse drug reactions (cADRs) attributed to lamotrigine and phenytoin.

  12. IMMEDIATE AND DELAYED HYPERSENSITIVITY REACTIONS TO LATEX GLOVES IN A DENTAL STUDENT. A case report.

    Directory of Open Access Journals (Sweden)

    Iliyana Stoeva

    2011-08-01

    Full Text Available The article presents a case of dental student with immediate and delayed hypersensitivity reaction to latex gloves. Symptoms appeared during the second year of regularly using of latex gloves. The student was with no history of allergies and no previous exposure to latex products.

  13. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.

    LENUS (Irish Health Repository)

    McCormack, Mark

    2011-03-24

    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.

  14. Evaluation of potential regulatory elements identified as DNase I hypersensitive sites in the CFTR gene

    DEFF Research Database (Denmark)

    Phylactides, M.; Rowntree, R.; Nuthall, H.

    2002-01-01

    hypersensitive sites (DHS) within the locus. We previously identified at least 12 clusters of DHS across the CFTR gene and here further evaluate DHS in introns 2,3,10,16,17a, 18, 20 and 21 to assess their functional importance in regulation of CFTR gene expression. Transient transfections of enhancer/reporter...

  15. Infection or metal hypersensitivity? The diagnostic challenge of failure in metal-on-metal bearings.

    LENUS (Irish Health Repository)

    Galbraith, John G

    2011-04-01

    The use of second generation metal-on-metal hip articulations has gained favour in the past few years. A hypersensitivity reaction to the metal-on-metal bearing, although rare, is a reported complication and is a novel mode of failure of these implants. Differentiating failure secondary to infection from failure secondary to metal hypersensitivity represents a significant diagnostic challenge. A retrospective review of all cases of hip arthroplasty using metal-on-metal bearings over a 5-year period at a tertiary referral centre identified 3 cases of failure secondary to metal hypersensitivity. Clinical presentation, serological markers, radiological imaging and histological analysis of all cases identified were evaluated. Histological analysis of periprosthetic tissue in all 3 cases identified characteristic features such as perivascular lymphocytic aggregates and chronic inflammation consistent with aseptic lymphocytic vasculitis-associated lesions (ALVAL). This study highlights that failure secondary to metal hypersensitivity must be considered in patients presenting with the reappearance of persistent pain, marked joint effusion, and the development of early osteolysis in the absence of infection.

  16. Pharmacological evaluation of NSAID-induced gastropathy as a "Translatable" model of referred visceral hypersensitivity.

    Science.gov (United States)

    Hummel, Michele; Knappenberger, Terri; Reilly, Meghan; Whiteside, Garth T

    2017-09-07

    To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice ( n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential (TRP), sodium and acid-sensing ion channels (ASICs) as well as opioid receptors and guanylate cyclase C (GC-C). Results showed that two opioids and a GC-C agonist, morphine, asimadoline and linaclotide, respectively, the TRP antagonists, AMG9810 and HC-030031 and the sodium channel blocker, carbamazepine, elicited a dose- and/or time-dependent attenuation of referred visceral hypersensitivity, while the ASIC blocker, amiloride, was ineffective at all doses tested. Together, these findings implicate opioid receptors, GC-C, and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly, these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties.

  17. Detection of systemic hypersensitivity to drugs using standard guinea pig assays.

    Science.gov (United States)

    Weaver, James L; Staten, David; Swann, Joslyn; Armstrong, George; Bates, Melissa; Hastings, Kenneth L

    2003-12-01

    The most commonly used assays designed to detect either skin or systemic immune-based hypersensitivity reactions are those using guinea pigs (GP). We obtained data from various FDA records to evaluate the correlation between GP assay results and reported post-marketing systemic hypersensitivity reactions. We examined the new drug application (NDA) reviews of approved drugs for the results of GP assays. Post-marketing human data were extracted from the FDA adverse event reporting system (AERS). Drug usage data were obtained from a commercial database maintained by IMS Health Inc. We found 83 (21%) of 396 drugs approved between 1978 and 1998 had reported GP test results. Among these 83 drugs, 14 (17%) were found to have positive results in at least one GP assay. Simple reporting index (RI) values for systemic hypersensitivity reactions were calculated from AERS data and usage to produce the index of adverse event reports per million shipping units of drug. A variety of definitions of positive human response were examined. A statistically significant association was seen for rash between post-marketing and clinical trials adverse event reports. No statistically significant associations between human data and GP test results were observed. These data suggest that standard GP assays have limited ability to predict human systemic hypersensitivity potential for pharmaceuticals.

  18. IL-1β-Dependent Activation of Dendritic Epidermal T Cells in Contact Hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Morten M; Lovato, Paola; Macleod, Amanda S

    2014-01-01

    Substances that penetrate the skin surface can act as allergens and induce a T cell-mediated inflammatory skin disease called contact hypersensitivity (CHS). IL-17 is a key cytokine in CHS and was originally thought to be produced solely by CD4(+) T cells. However, it is now known that several cell...

  19. Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection.

    Science.gov (United States)

    Descamps, V; Mahe, E; Houhou, N; Abramowitz, L; Rozenberg, F; Ranger-Rogez, S; Crickx, B

    2003-05-01

    Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.

  20. Making Sense of Metal Allergy and Hypersensitivity to Metallic Implants in Relation to Hand Surgery.

    Science.gov (United States)

    Christensen, Thomas J; Samant, Shefali A; Shin, Alexander Y

    2017-09-01

    All metals implanted into a biological system undergo some degree of corrosion depending upon its composition. The electrochemical process of corrosion produces free metal ions, which may activate the host's immune system through a variety of mechanisms. Whereas dermal metal hypersensitivity is common, affecting 10% to 15% of the population, the immune reaction from implanted metals is much less common (allergy and hypersensitivity producing a multitude of patient symptoms. Superficial symptoms may be mild to severe forms of dermatitis, urticaria, pruritus, and vasculitis, whereas deep sequelae include metallosis-related pseudotumor, implant loosening, and joint stiffness. Currently, there are clinical tests to evaluate patients for metal hypersensitivity, but there is little agreement regarding the ideal timing and clinical situation prompting the work-up of a patient for a metal allergy or hypersensitivity. An understanding of the epidemiology, etiology, basic science, diagnostic testing, and treatment of patients with suspected metal allergy, as it pertains to the current literature, will aid orthopedic and plastic surgeons of all subspecialties in the management of patients requiring metallic implants. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  1. Gender and dose dependent ovalbumin induced hypersensitivity responses in murine model of food allergy

    Science.gov (United States)

    While federal regulations mandate the labeling of major food allergens, allowable food allergen thresholds have yet to be determined. Therefore the aim of this project was to identify the lowest egg allergen ovalbumin (OVA) dose causing hypersensitization using a validated murine model. Mice were or...

  2. Systemic Immediate Hypersensitive Reactions after Treatment with Sweet Bee Venom: A Case Report

    Directory of Open Access Journals (Sweden)

    NaYoung Jo

    2015-12-01

    Full Text Available Objectives: A previous study showed that bee venom (BV could cause anaphylaxis or other hypersensitivity reactions. Although hypersensitivity reactions due to sweet bee venom (SBV have been reported, SBV has been reported to be associated with significantly reduced sensitization compared to BV. Although no systemic immediate hypersensitive response accompanied by abnormal vital signs has been reported with respect to SBV, we report a systemic immediate hypersensitive response that we experienced while trying to use SBV clinically. Methods: The patient had undergone BV treatment several times at other Oriental medicine clinics and had experienced no adverse reactions. She came to acupuncture & moxibustion department at Semyung university hospital of Oriental medicine (Je-cheon, Korea complaining of facial hypoesthesia and was treated using SBV injections, her first SBV treatment. SBV, 0.05 cc, was injected at each of 8 acupoints, for a total of 0.40 cc: Jichang (ST4, Daeyeong (ST5, Hyeopgeo (ST6, Hagwan (ST7, Yepung (TE17, Imun (TE21, Cheonghoe (GB2, and Gwallyeo (SI18. Results: The patient showed systemic immediate hypersensitive reactions. The main symptoms were abdominal pain, nausea and perspiration, but common symptoms associated with hypersensitivity, such as edema, were mild. Abdominal pain was the most long-lasting symptom and was accompanied by nausea. Her body temperature decreased due to sweating. Her diastolic blood pressure could not be measured on three occasions. She remained alert, though the symptoms persisted. The following treatments were conducted in sequence; intramuscular epinephrine, 1 mg/mL, injection, intramuscular dexamethasone, 5 mg/mL, injection, intramuscular buscopan, 20 mg/mL, injection, oxygen (O2 inhalation therapy, 1 L/minutes, via a nasal prong, and intravascular injection of normal saline, 1 L. After 12 hours of treatment, the symptoms had completely disappeared. Conclusion: This case shows that the use of SBV

  3. Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

    Directory of Open Access Journals (Sweden)

    Schurink Anouk

    2012-10-01

    Full Text Available Abstract Background Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with insect bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands. Methods Data on 200 Shetland pony mares and 146 Icelandic horses were collected according to a matched case–control design. Cases and controls were matched on various factors (e.g. region, sire to minimize effects of population stratification. Breed-specific genome-wide association studies were performed using 70 k single nucleotide polymorphisms genotypes. Bayesian variable selection method Bayes-C with a threshold model implemented in GenSel software was applied. A 1 Mb non-overlapping window approach that accumulated contributions of adjacent single nucleotide polymorphisms was used to identify associated genomic regions. Results The percentage of variance explained by all single nucleotide polymorphisms was 13% in Shetland pony mares and 28% in Icelandic horses. The 20 non-overlapping windows explaining the largest percentages of genetic variance were found on nine chromosomes in Shetland pony mares and on 14 chromosomes in Icelandic horses. Overlap in identified associated genomic regions between breeds would suggest interesting candidate regions to follow-up on. Such regions common to both breeds (within 15 Mb were found on chromosomes 3, 7, 11, 20 and 23. Positional candidate genes within 2 Mb from the associated windows were identified on chromosome 20 in both breeds. Candidate genes are within the equine lymphocyte antigen class II region, which evokes an immune response by recognizing many foreign molecules. Conclusions The genome-wide association

  4. Feasibility and potential utility of multicomponent exhaled breath analysis for predicting development of radiation pneumonitis after stereotactic ablative radiotherapy.

    Science.gov (United States)

    Moré, Jayaji M; Eclov, Neville C W; Chung, Melody P; Wynne, Jacob F; Shorter, Joanne H; Nelson, David D; Hanlon, Alexandra L; Burmeister, Robert; Banos, Peter; Maxim, Peter G; Loo, Billy W; Diehn, Maximilian

    2014-07-01

    In this prospective pilot study, we evaluated the feasibility and potential utility of measuring multiple exhaled gases as biomarkers of radiation pneumonitis (RP) in patients receiving stereotactic ablative radiotherapy (SABR) for lung tumors. Breath analysis was performed for 26 patients receiving SABR for lung tumors. Concentrations of exhaled nitric oxide (eNO), carbon monoxide (eCO), nitrous oxide (eN2O), and carbon dioxide (eCO2) were measured before and immediately after each fraction using real-time, infrared laser spectroscopy. RP development (CTCAE grade ≥2) was correlated with baseline gas concentrations, acute changes in gas concentrations after each SABR fraction, and dosimetric parameters. Exhaled breath analysis was successfully completed in 77% of patients. Five of 20 evaluable patients developed RP at a mean of 5.4 months after SABR. Acute changes in eNO and eCO concentrations, defined as percent changes between each pre-fraction and post-fraction measurement, were significantly smaller in RP versus non-RP cases (p = 0.022 and 0.015, respectively). In an exploratory analysis, a combined predictor of baseline eNO greater than 24 parts per billion and acute decrease in eCO less than 5.5% strongly correlated with RP incidence (p =0.0099). Neither eN2O nor eCO2 concentrations were significantly associated with RP development. Although generally higher in patients destined to develop RP, dosimetric parameters were not significantly associated with RP development. The majority of SABR patients in this pilot study were able to complete exhaled breath analysis. Baseline concentrations and acute changes in concentrations of exhaled breath components were associated with RP development after SABR. If our findings are validated, exhaled breath analysis may become a useful approach for noninvasive identification of patients at highest risk for developing RP after SABR.

  5. A Nomogram to Predict Radiation Pneumonitis, Derived From a Combined Analysis of RTOG 9311 and Institutional Data

    International Nuclear Information System (INIS)

    Bradley, Jeffrey D.; Hope, Andrew; El Naqa, Issam; Apte, Aditya M.S.; Lindsay, Patricia E.; Bosch, Walter D.Sc.; Matthews, John D.Sc.; Sause, William; Graham, Mary V.; Deasy, Joseph O.

    2007-01-01

    Purpose: To test the Washington University (WU) patient dataset, analysis of which suggested that superior-to-inferior tumor position, maximum dose, and D35 (minimum dose to the hottest 35% of the lung volume) were valuable to predict radiation pneumonitis (RP), against the patient database from Radiation Therapy Oncology Group (RTOG) trial 9311. Methods and Materials: The entire dataset consisted of 324 patients receiving definitive conformal radiotherapy for non-small-cell lung cancer (WU = 219, RTOG 9311 = 129). Clinical, dosimetric, and tumor location parameters were modeled to predict RP in the individual datasets and in a combined dataset. Association quality with RP was assessed using Spearman's rank correlation (r) for univariate analysis and multivariate analysis; comparison between subgroups was tested using the Wilcoxon rank sum test. Results: The WU model to predict RP performed poorly for the RTOG 9311 data. The most predictive model in the RTOG 9311 dataset was a single-parameter model, D15 (r = 0.28). Combining the datasets, the best derived model was a two-parameter model consisting of mean lung dose and superior-to-inferior gross tumor volume position (r = 0.303). An equation and nomogram to predict the probability of RP was derived using the combined patient population. Conclusions: Statistical models derived from a large pool of candidate models resulted in well-tuned models for each subset (WU or RTOG 9311), which did not perform well when applied to the other dataset. However, when the data were combined, a model was generated that performed well on each data subset. The final model incorporates two effects: greater risk due to inferior lung irradiation, and greater risk for increasing normal lung mean dose. This formula and nomogram may aid clinicians during radiation treatment planning for lung cancer

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-06-15

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

  8. The impact of radiation dose and fractionation on the risk factor of radiation pneumonitis on four radiation therapy oncology group (RTOG) lung cancer trials

    International Nuclear Information System (INIS)

    Roach, Mack; Pajak, Thomas F; Byhardt, Roger; Graham, Mary L; Asbell, Sucha O; Russell, Anthony H; Fu, Karen K; Urtasun, Raul C; Herskovic, Arnold M; Cox, James D

    1997-01-01

    Purpose/Objective: To assess the relationship between total dose of radiation delivered, the fractionation scheme used, age, and Karnofsky Performance Status (KPS) on the risk of moderate to severe (≥ Grade 2) radiation pneumonitis in patients treated with radiotherapy alone for lung cancer on four RTOG Trials. Materials and Methods: Between February of 1984 and April of 1989, 1701 patients with clinically localized (I-IIIb) lung cancer were entered on clinical trials employing radiotherapy alone. Twelve hundred and forty-seven patients were entered on RTOG 8311 or 8407 (phase I/II trials) and 454 patients were entered on RTOG 8321 or 8403 (phase III trials). RTOG 8403 and 8321 patients received once-a-day irradiation to 60 Gy. Patients treated on RTOG 8407 were treated with a concomitant boost technique in a non-randomized fashion to 64.8, 69.6, 74.4 or 79.2 Gy. Patients treated on RTOG 8407 were treated with a concomitant boost technique in a non-randomized fashion to 63 Gy or 70.2 Gy. All patients were assessed for the incidence of Grade 2-5, radiation pneumonitis. One hundred and seven (6%) of patients were either ineligible or canceled (n=60), or were excluded because of incomplete data (n=47). The factors evaluated included total dose of radiation, the fractionation scheme, age and pre-treatment KPS. Patients treated to doses ≥ 72 Gy were considered to have received high doses (72.0 - 81.6 Gy), while the remaining patients treated to doses < 72 Gy (57.6 - 71.9 Gy) were considered to have received standard dose radiation. For the this analysis, information regarding field size and baseline pulmonary function was not available. Results: Age, sex, stage distribution, and the percentage of patients with a KPS ≥90 were similar among the patients treated on these four studies. Patients receiving hyperfractionated radiotherapy to doses ≥ 72 Gy experienced a higher incidence of radiation pneumonitis ≥ Grade 2, than patients treated with standard doses < 72

  9. Common allergies do not influence the prevalence of cutaneous hypersensitivity reactions to antiepileptic drugs.

    Science.gov (United States)

    Bosak, Magdalena; Porębski, Grzegorz; Słowik, Agnieszka; Turaj, Wojciech

    2017-09-01

    The aim of the study was to establish whether the presence of common allergies increases the risk of drug-related hypersensitivity reactions among patients with epilepsy treated with antiepileptic drugs (AEDs). We studied 753 patients with epilepsy seen in tertiary outpatient epilepsy clinic. We obtained data related to epilepsy type, past and ongoing treatment with AEDs, occurrence of maculopapular exanthema or more serious cutaneous adverse reactions (Stevens-Johnson syndrome - SJS) and their characteristics. We noted an occurrence of allergic reactions unrelated to treatment with AED, including rash unrelated to AED, bronchial asthma, persistent or seasonal allergic rhinitis, atopic dermatitis, rash after specific food and other allergic reactions. There were 61 cases of AED-related cutaneous hypersensitivity reaction (including 3 cases of SJS) noted in association with 2319 exposures to AEDs (2.63%) among 55 out of 753 patients (7.3%). Cutaneous hypersensitivity reaction to AED was most commonly noted after lamotrigine (12.1%), carbamazepine (5.4%) and oxcarbazepine (4.1%). Prevalence of allergic reactions unrelated to AED was similar between patients with and without AED-related cutaneous hypersensitivity reaction (rash unrelated to AED: 16.4% vs. 10.2%; bronchial asthma: 1.8% vs. 0.1%; persistent allergic rhinitis: 7.3% vs. 10.2%; seasonal allergic rhinitis: 7.3% vs. 11.7%; atopic dermatitis: 0 vs. 0.7%; rash after specific food: 5.4% vs. 6.4%; other allergic reactions: 5.4% vs. 5.2%, respectively; P>0.1 for each difference). Presence of common allergies is not a significant risk factor for AED-related cutaneous hypersensitivity reaction among patients with epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Fatal hypersensitivity reaction to an oral spray of flurbiprofen: a case report.

    Science.gov (United States)

    Calapai, G; Imbesi, S; Cafeo, V; Ventura Spagnolo, E; Minciullo, P L; Caputi, A P; Gangemi, S; Milone, L

    2013-08-01

    Safety of the anti-inflammatory drug flurbiprofen is comparable with that of other non-steroidal anti-inflammatory drugs of the propionic acid class, which are commonly associated with gastrointestinal and renal side effects. Here we report a case of a fatal hypersensitivity reaction to an oral spray of flurbiprofen taken for sore throat. A 29-year-old man came to the emergency care unit reporting sore throat with an intense burning sensation associated with fever. Pharyngotonsillitis was diagnosed, and local treatment with oral flurbiprofen spray was prescribed. Immediately after using the spray, the patient experienced a severe reaction characterized by serious dyspnoea, followed by death. The cause of death was heart failure with acute asphyxia from oedema of the glottis. The cause of death was concluded to be hypersensitivity to flurbiprofen spray. Oral propionic acid derivatives have been associated with a relatively high frequency of allergic reactions. However, allergy to flurbiprofen has rarely been documented. Scientific literature reports two relevant cases of hypersensitivity reaction to flurbiprofen: in one case, a patient presented with a maculopapular rash 48 h after having taken oral flurbiprofen followed by angio-oedema and hypotension. In another case, a single oral dose of flurbiprofen caused itching and swelling around the eyes, redness and increased lacrimation. We describe, for the first time, a fatal case of hypersensitivity reaction to flurbiprofen oral spray. Hypersensitivity reactions to flurbiprofen are infrequent; however, health professionals should be aware of potential adverse reactions, even during topical administration as oral spray. © 2013 John Wiley & Sons Ltd.

  11. Hypersensitivity to DNA-damaging agents in primary degenerations of excitable tissue

    International Nuclear Information System (INIS)

    Robbins, J.H.

    1983-01-01

    Defects in DNA-repair mechanisms render xeroderma pigmentosum cells hypersensitive to killing by the uv-type of DNA-damaging agent. Some xeroderma pigmentosum patients develop a primary neuronal degeneration, and cell lines from patients with the earliest onset of neurodegeneration are the most sensitive to killing by uv radiation. These findings led to the neuronal DNA integrity theory which holds that when the integrity of neuronal DNA is destroyed by the accumulation of unrepaired DNA damaged spontaneously or by endogenous metabolites, the neurons will undergo a primary degeneration. Cells from patients with Cockayne syndrome, a demyelinating disorder with a primary retinal degeneration, are also hypersensitive to the uv-type of DNA-damaging agent. Cells from patients with the primary neuronal degeneration of ataxia telangiectasia are hypersensitive to the x-ray-type of DNA-damaging agent. Cells from other patients with primary degeneration of excitable tissue also have hypersensitivity to the x-ray-type of DNA-damaging agent. These disorders include (1) primary neuronal degenerations which are either genetic (e.g., Huntington disease, familial dysautonomia, Friedreich ataxia) or sporadic (e.g., Alzheimer disease, Parkinson disease), (2) primary muscle degenerations (e.g., Duchenne muscular dystrophy), and (3) a primary retinal degeneration (Usher syndrome). Death of excitable tissue in vivo in these radiosensitive diseases may result from unrepaired DNA. This hypersensitivity provides the basis for developing suitable presymptomatic and prenatal tests for these diseases, for elucidating their pathogenesis, and for developing future therapies. 119 references, 3 figures, 3 tables

  12. Use of cephalosporins in patients with immediate penicillin hypersensitivity: cross-reactivity revisited.

    Science.gov (United States)

    Lee, Q U

    2014-10-01

    A 10% cross-reactivity rate is commonly cited between penicillins and cephalosporins. However, this figure originated from studies in the 1960s and 1970s which included first-generation cephalosporins with similar side-chains to penicillins. Cephalosporins were frequently contaminated by trace amount of penicillins at that time. The side-chain hypothesis for beta-lactam hypersensitivity is supported by abundant scientific evidence. Newer generations of cephalosporins possess side-chains that are dissimilar to those of penicillins, leading to low cross-reactivity. In the assessment of cross-reactivity between penicillins and cephalosporins, one has to take into account the background beta-lactam hypersensitivity, which occurs in up to 10% of patients. Cross-reactivity based on skin testing or in-vitro test occurs in up to 50% and 69% of cases, respectively. Clinical reactivity and drug challenge test suggest an average cross-reactivity rate of only 4.3%. For third- and fourth-generation cephalosporins, the rate is probably less than 1%. Recent international guidelines are in keeping with a low cross-reactivity rate. Despite that, the medical community in Hong Kong remains unnecessarily skeptical. Use of cephalosporins in patients with penicillin hypersensitivity begins with detailed history and physical examination. Clinicians can choose a cephalosporin with a different side-chain. Skin test for penicillin is not predictive of cephalosporin hypersensitivity, while cephalosporin skin test is not sensitive. Drug provocation test by experienced personnel remains the best way to exclude or confirm the diagnosis of drug hypersensitivity and to find a safe alternative for future use. A personalised approach to cross-reactivity is advocated.

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

    Directory of Open Access Journals (Sweden)

    Daniela eWeth

    2015-04-01

    Full Text Available 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, neutralisation 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.

  14. Drug desensitization in the management of hypersensitivity reactions to monoclonal antibodies and chemotherapy.

    Science.gov (United States)

    Mezzano, Veronica; Giavina-Bianchi, Pedro; Picard, Matthieu; Caiado, Joana; Castells, Mariana

    2014-04-01

    Hypersensitivity reactions to monoclonal antibodies and chemotherapy, which may vary in severity from mild to life-threatening, can lead to their discontinuation and replacement by alternative agents that are often less effective, more toxic, and/or more expensive. Drug desensitization has emerged as the best treatment modality capable of allowing re-introduction of the hypersensitivity reaction-inducing medication in highly sensitized patients in need of first line therapies. In recent years, the availability of new anti-neoplastic drugs and therapeutic monoclonal antibodies has increased, as has the potential for hypersensitivity reactions. Development of desensitization protocols for these new medications requires a careful assessment of the potential risks and benefits. The purposes of this review are to provide an overview of the presentation of hypersensitivity reactions amenable to desensitization and to increase awareness of the indications for and outcomes of desensitization protocols. Rapid drug desensitization has proven to be a safe and effective way of administering first line therapy to patients with hypersensitivity reactions, providing an extremely powerful treatment modality for patients for whom alternative drugs are deemed unacceptable. Rapid drug desensitization protocols should be administered only by highly trained allergists and nurses who have experience in determining which reactions are amenable to desensitization, and can identify high risk patients and provide them with appropriate care. Efforts should be made to increase awareness of the remarkable safety and efficacy of rapid drug desensitization among non-allergists, especially in the fields of oncology and rheumatology, so as to favor its universal application. Development of desensitization units to provide state-of-the-art care is possible only through coordinated teamwork.

  15. Dendritic cell populations in patients with self-reported food hypersensitivity

    Directory of Open Access Journals (Sweden)

    Lied GA

    2011-05-01

    Full Text Available Gülen A Lied1,3,4,*, Petra Vogelsang2,*, Arnold Berstad1,4, Silke Appel2 1Institute of Medicine, 2Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Norway; 3Division of Gastroenterology, Department of Medicine; 4Section of Clinical Allergology, Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway *These authors contributed equally to this workAbstract: Self-reported hypersensitivity to food is a common condition and many of these patients have indications of intestinal immune activation. Dendritic cells (DCs are recognized as the most potent antigen-presenting cells involved in both initiating immune responses and maintaining tolerance. The aims of this study were to evaluate the DC populations with their phenotype and T cell stimulatory capacity in patients with food hypersensitivity and to study its relationship with atopic disease. Blood samples from 10 patients with self-reported food hypersensitivity, divided into atopic and nonatopic subgroups, and 10 gender- and age-matched healthy controls were analyzed by flow cytometry using the Miltenyi Blood Dendritic cells kit. Monocyte-derived DCs (moDCs were evaluated concerning their phenotype and T cell stimulatory capacity. DC populations and cell surface markers were not significantly different between patients and healthy controls, but moDCs from atopic patients expressed significantly more CD38 compared to moDCs from nonatopic patients. Moreover, lipopolysaccharide stimulated moDCs from atopic patients produced significantly more interleukin-10 compared to nonatopic patients. CD38 expression was correlated to total serum immunoglobulin E levels. These findings support the notion of immune activation in some patients with self-reported food hypersensitivity. They need to be confirmed in a larger cohort.Keywords: food hypersensitivity, atopy, dendritic cells, CD38

  16. Fasting mitigates immediate hypersensitivity: a pivotal role of endogenous D-beta-hydroxybutyrate.

    Science.gov (United States)

    Nakamura, Shigeru; Hisamura, Ryuji; Shimoda, Sachiko; Shibuya, Izumi; Tsubota, Kazuo

    2014-01-01

    Fasting is a rigorous type of dietary restriction that is associate with a number of health benefits. During fasting, ketone bodies significantly increase in blood and become major body fuels, thereby sparing glucose. In the present study, we investigated effects of fasting on hypersensitivity. In addition, we also investigated the possible role of D-beta-hydroxybutyrate provoked by fasting in the attenuation of immediate hypersensitivity by fasting. Effects of fasting on systemic anaphylaxis were examined using rat model of toluene 2, 4-diisocyanate induced nasal allergy. In addition to food restriction, a ketogenic high-fat and low-carbohydrate diet that accelerates fatty acid oxidation and systemic instillation of D-beta-hydroxybutyrate were employed to elevate internal D-beta-hydroxybutyrate concentration. We assessed relationship between degranulation of rat peritoneal mast cells and internal D-beta-hydroxybutyrate concentration in each treatment. Changes in [Ca(2+)]i responses to compound 48/80 were analyzed in fura 2-loaded rat peritoneal mast cells derived from the ketogenic diet and fasting. Immediate hypersensitivity reaction was significantly suppressed by fasting. A significant reduction in mast cells degranulation, induced by mast cell activator compound 48/80, was observed in rat peritoneal mast cells delivered from the 24 hours fasting treatment. In addition, mast cells delivered from a ketogenic diet and D-beta-hydroxybutyrate infusion treatment also had reduced mast cell degranulation and systemic D-beta-hydroxybutyrate concentrations were elevated to similar extent as the fasting state. The peak increase in [Ca(2+)]i was significantly lower in the ketogenic diet and fasting group than that in the control diet group. The results of the present study demonstrates that fasting suppress hypersensitivity reaction, and indicate that increased level of D-beta-hydroxybutyrate by fasting plays an important role, via the stabilization of mast cells, in

  17. Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD database and the GALEN platform. The Galenda project.

    Science.gov (United States)

    Bousquet, P-J; Demoly, P; Romano, A; Aberer, W; Bircher, A; Blanca, M; Brockow, K; Pichler, W; Torres, M J; Terreehorst, I; Arnoux, B; Atanaskovic-Markovic, M; Barbaud, A; Bijl, A; Bonadonna, P; Burney, P G; Caimmi, S; Canonica, G W; Cernadas, J; Dahlen, B; Daures, J-P; Fernandez, J; Gomes, E; Gueant, J-L; Kowalski, M L; Kvedariene, V; Mertes, P-M; Martins, P; Nizankowska-Mogilnicka, E; Papadopoulos, N; Ponvert, C; Pirmohamed, M; Ring, J; Salapatas, M; Sanz, M L; Szczeklik, A; Van Ganse, E; De Weck, A L; Zuberbier, T; Merk, H F; Sachs, B; Sidoroff, A

    2009-02-01

    Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments.

  18. Severe nivolumab-induced pneumonitis preceding durable clinical remission in a patient with refractory, metastatic lung squamous cell cancer: a case report

    Directory of Open Access Journals (Sweden)

    Hong Li

    2017-02-01

    Full Text Available Abstract Background Programmed cell death 1 (PD-1 and its ligand 1 (PD-L1 inhibitors have quickly become standard of care for patients with advanced non-small cell lung cancer and increasing numbers of other cancer types. In this report, we discuss the clinical history, pathological evaluation, and genomic findings in a patient with metastatic lung squamous cell cancer (SCC who developed severe nivolumab-induced pneumonitis preceding durable clinical remission after three doses of nivolumab. Case presentation A patient with chemotherapy-refractory, metastatic lung SCC developed symptomatic pneumonitis by week 4 after nivolumab treatment, concurrently with onset of a potent antitumor response. Despite discontinuation of nivolumab after three doses and the use of high dose oral corticosteroids for grade 3 pneumonitis, continued tumor response to a complete remission by 3 months was evident by radiographic assessment. At the time of this submission, the patient has remained in clinical remission for 14 months. High PD-L1 expression by immunohistochemistry staining was seen in intra-alveolar macrophages and viable tumor cells in the pneumonitis and recurrent tumor specimens, respectively. Tumor genomic profiling by FoundationOne targeted exome sequencing revealed a very high tumor mutation burden (TMB corresponding to 95–96 percentile in lung SCC, i.e., 87.4–91.0 and 82.9 mut/Mb, respectively, in pre- and post-nivolumab tumor specimens. Except for one, the 13 functional genomic alterations remained the same in the diagnostic, recurrent, and post-treatment, relapsed tumor specimens, suggesting that nivolumab reset the patient’s immune system against one or more preexisting tumor-associated antigens (TAAs. One potential TAA candidate is telomerase reverse transcriptase (TERT in which an oncogenic promoter -146C>T mutation was detected. Human leukocyte antigen (HLA typing revealed HLA-A*0201 homozygosity, which is the prevalent HLA class I

  19. The diagnostic accuracy of the atopy patch test in diagnosing hypersensitivity to cow's milk and hen's egg in unselected children with and without atopic dermatitis

    DEFF Research Database (Denmark)

    Osterballe, Morten; Andersen, Klaus E; Bindslev-Jensen, Carsten

    2004-01-01

    BACKGROUND: Previous studies have suggested that the atopy patch test (APT) may make oral challenge superfluous in diagnosing children with food hypersensitivity. OBJECTIVE: To investigate the clinical relevance of APT in predicting hypersensitivity to cow's milk and hen's egg in 486 unselected...... children 3 years of age. METHOD: The children were examined by APT, skin prick (SPT), histamine release (HR), and specific IgE followed by oral challenge when hypersensitivity to cow's milk or hen's egg was suspected. RESULTS: Food hypersensitivity confirmed by oral challenge was 1.6% to hen's egg and 0.......6% to cow's milk. No hypersensitivity to cow's milk or hen's egg was predicted by APT alone. CONCLUSION: APT could not predict food hypersensitivity not predicted by SPT, HR, or specific IgE. Thus, APT cannot be recommended in daily practice for the diagnosis of hypersensitivity to cow's milk and hen's egg...

  20. Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

    International Nuclear Information System (INIS)

    Chi, Yan; Liu, Xin-Guang; Wang, Hua-Hong; Li, Jun-Xia; Li, Yi-Xuan

    2012-01-01

    Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT 4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT 4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT 4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg −1 ·day −1 , days 36-42), tegaserod (1 mg·kg −1 ·day −1 , day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT 4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT 4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level

  1. Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

    Directory of Open Access Journals (Sweden)

    Chi Yan

    2012-10-01

    Full Text Available Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05 and increased 5-HT4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05. Treatment with fluoxetine (10 mg·kg-1·day-1, days 36-42, tegaserod (1 mg·kg-1·day-1, day 43, or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01 but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654. These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.

  2. The correlation between clinical factors and radiation pneumonitis in advanced stage non-small-cell lung cancer treated with concurrent radiochemotherapy

    International Nuclear Information System (INIS)

    Han Lei; Lu Bing; Fu Heyi; Hu Yinxiang; Gan Jiaying; Li Huiqin

    2011-01-01

    Objective: To evaluate clinical factors as predictors of radiation pneumonitis (RP)in advanced stage non-small cell lung cancer (NSCLC) patients treated with concurrent radio chemotherapy when gross tumor volume is 70 Gy. Methods: Data of 84 patients with histologically proved NSCLC treated with 3DCRT or IMRT were collected. To evaluate the correlation between clinical parameters and radiation pneumonitis (RP). The clinical parameters were considered: pathological type, therapy agents, age,gender, stage, karnofsky performance status (KPS), smoking status, diabetes, chronic obstructive pulmonary disease (COPD). Results: The occurrence of grade 1, 2 RP was 63%, 33%, respectively. In univariate analysis, diabetes was significantly associated with RP of ≥ grade 1(χ 2 =4.03, P = 0.045)and ≥grade 2(χ 2 = 15.59, P =0.000). KPS was significantly associated with RP of ≥grade 1(χ 2 =3.98, P = 0.046)and ≥grade 2(χ 2 = 5.21, P = 0.023). In logistic multivariate analysis, diabetes was significantly associated with RP of ≥grade 1(χ 2 =5.50, P =0.019)and ≥grade 2(χ 2 = 12.92, P =0.000). KPS was significantly associated with RP of ≥ grade 1(χ 2 = 6.29, P = 0.012)and ≥ grade 2(χ 2 = 6.61, P =0.010). Conclusion: The definite statistical significant risk factors of RP are diabetes and KPS. (authors)

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

    Directory of Open Access Journals (Sweden)

    Cristi L. Galindo

    2009-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-01

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

  5. Updated assessment of the six-minute walk test as predictor of acute radiation-induced pneumonitis

    International Nuclear Information System (INIS)

    Mao Jingfang; Zhang Junan; Zhou Sumin; Das, Shiva; Hollis, Donna R.; Folz, Rodney J.; Wong, Terence Z.; Marks, Lawrence B.

    2007-01-01

    Purpose: To assess the utility of the 6-minute walk test (6MWT) as a predictor of symptomatic radiation-induced pneumonitis (RP). Methods: As part of a prospective trial to study radiation-induced lung injury, 53 patients receiving thoracic radiotherapy (RT) underwent a pre-RT 6MWT, pulmonary function tests (PFTs), and had ≥3-month follow-up for prospective assessment of Grade 2 or worse RP (requiring medications or worse). Dosimetric parameters (e.g., the percentage of lung receiving ≥30 Gy) were extracted from the lung dose-volume histogram. The correlations between the 6MWT and PFT results were assessed using Pearson's correlation. The receiver operating characteristic technique was used in patient subgroups to evaluate the predictive capacities for RP of the dosimetric parameters, 6MWT results, and PFT results, or the combination (using discriminant analysis) of all three metrics. ROCKIT software was used to compare the receiver operating characteristic areas between each predictive model. The association of the decline in 6MWT with the development of RP was evaluated using Fisher's exact test. Results: The pre-RT PFT and 6MWT results correlated weakly (r = 0.44-0.57, p ≤ 0.001), suggesting that they measure somewhat different physiologic functions. Of the 53 patients, 9 (17%) developed RP. The dose-volume histogram-based dosimetric parameters were the best single-metric model for predicting RP (e.g., percentage of lung receiving ≥30 Gy, receiver operating characteristic area 0.73, p = 0.03). Including the PFT or 6MWT results with the percentage of lung receiving ≥30 Gy did not improve the predictions. The predictive abilities of dosimetric-based models improved when the analysis was restricted to those patients whose tumors were not causing regional lung dysfunction. No correlation was found between the decline in the 6MWT result and the RP rate (p = 0.6). Conclusion: Although the PFTs and 6MWT are related to each other, the correlation coefficients

  6. Lymphocyte mediators of delayed hypersensitivity; the early phase cells

    Energy Technology Data Exchange (ETDEWEB)

    Lefford, M J; McGregor, D D [Trudeau Inst., Saranac Lake, N.Y. (USA)

    1978-04-01

    Inbred rats were immunized with living Bacillus Calmette-Guerin (BCG) and lymphocytes which mediate tuberculin DTH and anti-tuberculosis immunity were found 10 days later in the draining lymph nodes, thoracic duct, blood, spleen, and acute peritoneal exudates. The lymphocytes that mediated DTH incorporated /sup 3/HT in vitro, were large in size, sensitive to vinblastine but relatively resistant to irradiation, and had a short effective lifespan in syngeneic recipients. These properties characterize the cells as short-lived, nonrecirculating immunoblasts. In some experimental situations it was possible to dissociate the expression of DTH and immunity following the transfer of sensitized lymphocytes.

  7. Involvement of ethylene in lesion development and systemic acquired resistance in tobacco during the hypersensitive reaction to tobacco mosaic virus

    NARCIS (Netherlands)

    Knoester, M.; Linthorst, H.J.M.; Bol, J.F.; Loon, L.C. van

    2001-01-01

    Different approaches were taken to investigate the significance of ethylene in lesion development and systemic acquired resistance (SAR) in tobacco (Nicotiana tabacum) reacting hypersensitively to tobacco mosaic virus (TMV). Gaseous ethylene, the ethylene precursor 1-aminocyclopropane-1-carboxylic

  8. The retreatment of carboplatin via high-dose intraperitoneal chemotherapy in patients with a history of a hypersensitivity reaction

    NARCIS (Netherlands)

    Kerkhof, M.H.; Ruiz Zapata, A.M.; Bril, H.; Bleeker, M.C.G.; Belien, J.A.M.; Stoop, R.; Helder, M.N.

    2014-01-01

    A hypersensitivity reaction attributed to platinum-based chemotherapy is a relatively common occurrence. Hyperthermic intraperitoneal chemotherapy potentially facilitates the safe retreatment of platinum therapy following this complication. We describe 3 ovarian cancer patients who were successfully

  9. Hypersensitivity to norepinephrine in vasa deferentia from diabetic rats. Possible participation of metabolic products of arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Peredo, H; Agostini, M D; Gimeno, M F; Borda, E S

    1984-08-01

    Contractile responses to norepinephrine of the vas deferens isolated from normal and diabetic rats as well as tissue radio-conversion of exogenous arachidonic acid, were studied. Vasa deferentia from rats with acute streptozotocin-induced diabetes showed hypersensitivity to exogenous norepinephrine (NE). This increased contractile response was associated with the interaction of the agonist with alpha adrenoceptors. Inhibitors of cyclooxygenase increased and inhibitors of lipoxygenase(s) abolished the enhanced response to NE of diabetic vas deferens. Vasa deferentia from both normal and diabetic rats, converted (1-/sup 14/C)-arachidonic acid (AA) into PGF, PGE, PGD and thromboxane (TX) B2, but the % of AA metabolites formed was significantly higher in the diabetic than in the normal condition. Moreover, the predominant prostanoid generated by tissue preparations from diabetic animals was PGD2. Taken together the present experimental findings indicate that preparations from rats with acute streptozotocin-induced diabetes have an augmented reactivity towards NE, which appeared associated with changes in metabolites of AA generated via cyclooxygenase and lipoxygenase catalized pathways.

  10. PhyloChip microarray analysis reveals altered gastrointestinal microbial communities in a rat model of colonic hypersensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, T.A.; Holmes, S.; Alekseyenko, A.V.; Shenoy, M.; DeSantis, T.; Wu, C.H.; Andersen, G.L.; Winston, J.; Sonnenburg, J.; Pasricha, P.J.; Spormann, A.

    2010-12-01

    Irritable bowel syndrome (IBS) is a chronic, episodic gastrointestinal disorder that is prevalent in a significant fraction of western human populations; and changes in the microbiota of the large bowel have been implicated in the pathology of the disease. Using a novel comprehensive, high-density DNA microarray (PhyloChip) we performed a phylogenetic analysis of the microbial community of the large bowel in a rat model in which intracolonic acetic acid in neonates was used to induce long lasting colonic hypersensitivity and decreased stool water content and frequency, representing the equivalent of human constipation-predominant IBS. Our results revealed a significantly increased compositional difference in the microbial communities in rats with neonatal irritation as compared with controls. Even more striking was the dramatic change in the ratio of Firmicutes relative to Bacteroidetes, where neonatally irritated rats were enriched more with Bacteroidetes and also contained a different composition of species within this phylum. Our study also revealed differences at the level of bacterial families and species. The PhyloChip is a useful and convenient method to study enteric microflora. Further, this rat model system may be a useful experimental platform to study the causes and consequences of changes in microbial community composition associated with IBS.

  11. THE IMMUNOPATHOBIOLOGY OF SYPHILIS: THE MANIFESTATIONS AND COURSE OF SYPHILIS ARE DETERMINED BY THE LEVEL OF DELAYED-TYPE HYPERSENSITIVITY

    Science.gov (United States)

    Carlson, J. Andrew; Dabiri, Ganary; Cribier, Bernard; Sell, Stewart

    2013-01-01

    Syphilis has plagued mankind for centuries and is currently resurgent in the Western hemisphere. While there has been a significant reduction of tertiary disease, and recognition of facilitative interactions with HIV infection, the natural history of syphilis has remained largely unchanged; thus, new strategies are required to more effectively combat this pathogen. The immunopathologic features of experimental syphilis in the rabbit; the course, stages, and pathology of human syphilis; and a comparison of human syphilis with leprosy suggest that the clinical course of syphilis and its tissue manifestations are determined by the balance between delayed type hypersensitivity (DTH) and humoral immunity to the causative agent, Treponema pallidum. A strong DTH response is associated with clearance of the infecting organisms in a well-developed chancre, whereas a cytotoxic T-cell response or strong humoral antibody response is associated with prolonged infection and progression to tertiary disease. Many of the protean symptoms/appearances of secondary and tertiary human syphilis are manifestations of immune reactions that fail to clear the organism, due to a lack of recruitment and more importantly, activation of macrophages by sensitized CD4 T-cells. The Bacillus Calmette Guerin (BCG) vaccination can enhance DTH and has been shown to produce a low, but measurable beneficial effect in the prevention of leprosy, a disease that shows a disease spectrum with characteristics in common with syphilis. In the prevention of syphilis, a potential vaccine protective against syphilis should be designed to augment the DTH response. PMID:21694502

  12. Effect of Schizonepeta tenuifolia extract on mast cell-mediated immediate-type hypersensitivity in rats.

    Science.gov (United States)

    Shin, T Y; Jeong, H J; Jun, S M; Chae, H J; Kim, H R; Baek, S H; Kim, H M

    1999-11-01

    We investigated the effect of an aqueous extract of Schizonepeta tenuifolia (STAE) on mast cell-mediated immediate-type hypersensitivity. STAE inhibited systemic allergic reaction induced by compound 48/80 in rats dose-dependently. STAE also inhibited plasma histamine levels induced by compound 48/80. STAE inhibited local allergic reaction activated by anti-dinitrophenyl (DNP) IgE. In addition, STAE does-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. However, STAE had a significant enhancing effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) production from RPMC. These results indicate that STAE inhibits immediate-type hypersensitivity and suggest that STAE can selectively activate the TNF-alpha production from RPMC.

  13. Immunotherapy using regulatory T cells in cancer suggests more flavors of hypersensitivity type IV.

    Science.gov (United States)

    Pakravan, Nafiseh; Hassan, Zuhair Mohammad

    2018-03-01

    Regulatory T cells (Tregs) profoundly affect tumor microenvironment and exert dominant suppression over antitumor immunity in response to self-antigen expressed by tumor. Immunotherapy targeting Tregs lead to a significant improvement in antitumor immunity. Intradermal injection of tumor antigen results in negative delayed-type hypersensitivity (DTH) type IV. However, anti-Tregs treatment/use of adjuvant along with tumor antigens turns DTH to positive. Considering Tregs as the earliest tumor sensor/responders, tumor can be regarded as Treg-mediated type IV hypersensitivity and negative DTH to tumor antigen is due to anti-inflammatory action of Tregs to tumor antigens at the injection site. Such a view would help us in basic and clinical situations to testify a candidate vaccine via dermal administration and evaluation of Treg proportion at injection site.

  14. [Epidemiology of contact hypersensitivity to rubber components in manufacturers of automobile tires at the Stomil plant].

    Science.gov (United States)

    Rubisz-Brzezińska, J; Bogdanowski, T; Brzezińska-Wcisło, L; Mozdzanowska, K; Bajcar, S

    1990-01-01

    Dermatological examination and patch tests with 34 rubber components were carried out in 114 tire manufacturers, 78 women and 36 men aged 29 years on average, with a mean duration of work in the plant 7 years. For correct interpretation of the obtained results patch tests with the same components were done in two control groups that is in 120 healthy subjects and 120 patients with contact dermatitis. Patch tests with proper concentrations of the studied components were evaluated after 48, 72 and 96 hours. Positive patch tests were found most frequently with antioxidants--16.6% (including IPPD--8.6%), followed by vulcanization accelerators--10.6%, and other rubber components--11.4% in all. During about 3 years of follow-up in 4 manufacturers contact allergic eczema was noted and polyvalent hypersensitivity to antioxidants and vulcanization accelerators without clinical manifestations of this hypersensitivity was diagnosed in 3 other subjects.

  15. Dysmenorrhoea is associated with hypersensitivity in the sigmoid colon and rectum

    DEFF Research Database (Denmark)

    Brinkert, Willem; Dimcevski, Georg; Arendt-Nielsen, Lars

    2007-01-01

    if dysmenorrhoea is associated with hypersensitivity in the referred somatic skin area or in the large bowel, i.e., viscero-visceral hyperalgesia. We measured skin sensitivity in the referred area of the sigmoid colon as well as stimulus-response relationships in the sigmoid colon and rectum. The latter were...... measured using mechanical (balloon) distension applied via a Barostat in 11 dysmenorrhoea patients without gastro-intestinal complaints and 10 healthy and age matched women, again without gastrointestinal complaints. We found no skin hypersensitivity in the colonic referred area. In contrast, significantly...... lower distension volumes were seen at each threshold in dysmenorrhoea patients, particularly in the sigmoid colon. The mean reduction in colonic distension volume thresholds for dysmenorrhoea patients vs. controls was 57% at the detection threshold and 39% at the pain threshold. There were...

  16. Perceived food hypersensitivity relates to poor asthma control and quality of life in young non-atopic asthmatics.

    Directory of Open Access Journals (Sweden)

    Jennifer Johnson

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

  17. Perceived food hypersensitivity relates to poor asthma control and quality of life in young non-atopic asthmatics.

    Science.gov (United States)

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

    2015-01-01

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

  18. Minocycline Prevents Muscular Pain Hypersensitivity and Cutaneous Allodynia Produced by Repeated Intramuscular Injections of Hypertonic Saline in Healthy Human Participants.

    Science.gov (United States)

    Samour, Mohamad Samir; Nagi, Saad Saulat; Shortland, Peter John; Mahns, David Anthony

    2017-08-01

    Minocycline, a glial suppressor, prevents behavioral hypersensitivities in animal models of peripheral nerve injury. However, clinical trials of minocycline in human studies have produced mixed results. This study addressed 2 questions: can repeated injections of hypertonic saline (HS) in humans induce persistent hypersensitivity? Can pretreatment with minocycline, a tetracycline antibiotic with microglial inhibitory effects, prevent the onset of hypersensitivity? Twenty-seven healthy participants took part in this double-blind, placebo-controlled study, consisting of 6 test sessions across 2 weeks. At the beginning of every session, pressure-pain thresholds of the anterior muscle compartment of both legs were measured to determine the region distribution and intensity of muscle soreness. To measure changes in thermal sensitivity in the skin overlying the anterior muscle compartment of both legs, quantitative sensory testing was used to measure the cutaneous thermal thresholds (cold sensation, cold pain, warm sensation, and heat pain) and a mild cooling stimulus was applied to assess the presence of cold allodynia. To induce ongoing hypersensitivity, repeated injections of HS were administered into the right tibialis anterior muscle at 48-hour intervals. In the final 2 sessions (days 9 and 14), only sensory assessments were done to plot the recovery after cessation of HS administrations and drug washout. By day 9, nontreated participants experienced a significant bilateral increase in muscle soreness (P minocycline-treated participants experienced a bilateral 70% alleviation in muscle soreness (P minocycline-treated participants showed cold allodynia. This study showed that repeated injections of HS can induce a hypersensitivity that outlasts the acute response, and the development of this hypersensitivity can be reliably attenuated with minocycline pretreatment. Four repeated injections of HS at 48-hour intervals induce a state of persistent hypersensitivity in

  19. Pain hypersensitivity in congenital blindness is associated with faster central processing of C-fibre input

    DEFF Research Database (Denmark)

    Slimani, H.; Plaghki, L.; Ptito, M.

    2016-01-01

    Background We have recently shown that visual deprivation from birth exacerbates responses to painful thermal stimuli. However, the mechanisms underlying pain hypersensitivity in congenital blindness are unclear. Methods To study the contribution of Aδ- and C-fibres in pain perception, we measure...... The increased sensitivity to painful thermal stimulation in congenital blindness may be due to more efficient central processing of C-fibre–mediated input, which may help to avoid impending dangerous encounters with stimuli that threaten the bodily integrity....

  20. [Hypersensitivity to platinum salts and taxanes: The value of skin tests and tolerance induction procedures].

    Science.gov (United States)

    Brault, F; Waton, J; Poreaux, C; Schmutz, J-L; Barbaud, A

    2017-11-01

    The rate of hypersensitivity reactions to platinum salts (PS) and taxanes (TX) is on the increase. The aim of our study was to show the value of skin testing and efficacy of rapid drug desensitization. This was a retrospective study conducted between January 2007 and February 2016 in patients consulting for immediate or delayed hypersensitivity to PS and TX. Skin prick tests (pT) and intradermal reaction tests (IDR) were performed according to the ENDA/EAACI recommendations. We used a 12-step desensitization protocol for rapid drug desensitization. Among the 99 patients included (30 men, 69 women, age 60.4) PS were suspected in 86 cases and taxanes in 13 cases. Skin tests were positive in 25 patients (7 pT, 18 IDR), 23 for platinum salts and 2 for taxanes. Rapid drug desensitization was proposed in 50 patients and performed in 33 (30 PS and 3 TX), proved effective in 29 patients, with protocol adaptation being necessary in 7 cases, and was ineffective in 4 patients. The skin tests for the latter 4 patients were positive. Seventy-five percent of patients with positive skin tests to oxaliplatin presented hypersensitivity reactions during desensitization, i.e. twice as many as patients having negative skin tests. Two percent of patient for PS and 7% for TX had cross reactivity. This French study confirms the efficacy of the 12-step protocol that allows patients to receive chemotherapy after hypersensitivity reaction. Skin test permits the detection of cross-reactions but their practice must be considered based on the patient's history. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Development of mechanical hypersensitivity in rats during heroin and ethanol dependence: alleviation by CRF₁ receptor antagonism.

    Science.gov (United States)

    Edwards, Scott; Vendruscolo, Leandro F; Schlosburg, Joel E; Misra, Kaushik K; Wee, Sunmee; Park, Paula E; Schulteis, Gery; Koob, George F

    2012-02-01

    Animal models of drug dependence have described both reductions in brain reward processes and potentiation of stress-like (or anti-reward) mechanisms, including a recruitment of corticotropin-releasing factor (CRF) signaling. Accordingly, chronic exposure to opiates often leads to the development of mechanical hypersensitivity. We measured paw withdrawal thresholds (PWTs) in male Wistar rats allowed limited (short access group: ShA) or extended (long access group: LgA) access to heroin or cocaine self-administration, or in rats made dependent on ethanol via ethanol vapor exposure (ethanol-dependent group). In heroin self-administering animals, after transition to LgA conditions, thresholds were reduced to around 50% of levels observed at baseline, and were also significantly lower than thresholds measured in animals remaining on the ShA schedule. In contrast, thresholds in animals self-administering cocaine under either ShA (1 h) or LgA (6 h) conditions were unaltered. Similar to heroin LgA rats, ethanol-dependent rats also developed mechanical hypersensitivity after eight weeks of ethanol vapor exposure compared to non-dependent animals. Systemic administration of the CRF1R antagonist MPZP significantly alleviated the hypersensitivity observed in rats dependent on heroin or ethanol. The emergence of mechanical hypersensitivity with heroin and ethanol dependence may thus represent one critical drug-associated negative emotional state driving dependence on these substances. These results also suggest a recruitment of CRF-regulated nociceptive pathways associated with escalation of intake and dependence. A greater understanding of relationships between chronic drug exposure and pain-related states may provide insight into mechanisms underlying the transition to drug addiction, as well as reveal new treatment opportunities. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Hypersensitivity to mechanical and intra-articular electrical stimuli in persons with painful temporomandibular joints

    DEFF Research Database (Denmark)

    Ayesh, Emad; Jensen, Troels Staehelin; Svensson, P

    2007-01-01

    This study tested whether persons with TMJ arthralgia have a modality-specific and site-specific hypersensitivity to somatosensory stimuli assessed by quantitative sensory tests (QST). Forty-three healthy persons and 20 with TMJ arthralgia participated. The QST consisted of: sensory and pain dete...... of sensitization of the TMJs as well as central nociceptive pathways. QST may facilitate a mechanism-based classification of temporomandibular disorders. Udgivelsesdato: 2007-Dec...

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  5. Enhancement of cutaneous delayed hypersensitivity reactions by a single exposure to UV-A or PUVA

    International Nuclear Information System (INIS)

    Moberg, S.; Mobacken, H.

    1982-01-01

    The influence of irradiation with UV-A and PUVA (8-methoxy-psoralen and UV-A) on delayed hypersensitivity reactions to microbial antigens was studied in healthy human individuals. Skin reactions to Candida albicans antigen and PPD were enhanced by UV-A als well as by PUVA compared with nonirradiated tests. A statistically significant difference was reached with UV-A for both antigens. For PUVA, erythemogenic doses to Candida tests produced a significant increase of response. (orig.)

  6. Hypersensitivity to aeroallergens in adult patients with atopic dermatitis develops due to the different immunological mechanisms.

    Science.gov (United States)

    Samochocki, Zbigniew; Owczarek, Witold; Rujna, Paweł; Raczka, Alicja

    2007-01-01

    Atopic dermatitis (AD) is a disease with a complex pathomechanism, it is very difficult to establish the exact factors which can either trigger or exacerbate the disease. Knowledge of the mechanisms involved in AD development can be increased by, among others, applying new diagnostic tests and careful assessment of the results obtained. The aim of this study was to determine the allergic mechanisms of hypersensitivity to selected aeroallergens in patients with AD. The study comprised 109 AD patients. In all the patients the total IgE level was measured and atopy patch tests and skin prick tests were performed. We also assessed the presence of specific IgE against house dust mite, birch-tree, mixed grass pollen and cat dander. The highest incidence of positive results was found for house dust mite allergens, irrespective of the test employed. Analysing hypersensitivity to all the examined allergens we revealed the presence of allergic mechanisms in 85.3% of the patients. In 30.2% of the examined individuals we proved a type I immunological response, in 45.9% -- both types I and IV in 9.2% -- only type IV in one patient. In 14.7% of the patients the results of all the tests performed were negative. Analysing hypersensitivity to particular aeroallergens, negative test results to house dust mite were observed in 25.8% of the patients. The percentage of positive results for birch pollen, grass pollen and cat dander were 45.0, 44.1 and 53.2, respectively. Analysis of the results showed that allergic reactions to the same aeroallergens may develop via different mechanisms. We also revealed that the coexistence of various mechanisms involved in the development of hypersensitivity to a particular aeroallergen may occur in individual patients.

  7. Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats

    OpenAIRE

    Alison Diesel

    2017-01-01

    Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly “feline atopic syndrome” when compared to...

  8. Piezo2: A Candidate Biomarker for Visceral Hypersensitivity in Irritable Bowel Syndrome?

    OpenAIRE

    Bai, Tao; Li, Ying; Xia, Jing; Jiang, Yudong; Zhang, Lei; Wang, Huan; Qian, Wei; Song, Jun; Hou, Xiaohua

    2017-01-01

    Background/Aims Currently, there exists no biomarker for visceral hypersensitivity in irritable bowel syndrome (IBS). Piezo proteins have been proven to play an important role in the mechanical stimulation to induce visceral pain in other tissues and may also be a biomarker candidate. The aim of this study was to test the expressions of Piezo1 and Piezo2 proteins in the intestinal epithelial cells from different intestinal segments and to explore the correlation between Piezo proteins express...

  9. Exploring the Hypersensitivity of PTEN Deleted Prostate Cancer Stem Cells to WEE1 Tyrosine Kinase Inhibitors

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-14-1-0251 TITLE: Exploring the Hypersensitivity of PTEN Deleted Prostate Cancer Stem Cells to WEE1 Tyrosine Kinase... Tyrosine Kinase Inhibitors 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0251 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Kiran Mahajan 5d...ABSTRACT Central to all cycling cells-including prostate cancer stem cells- is the expression of WEE1 tyrosine kinase. WEE1 monitors duplication of

  10. Desensitization to ceftaroline in a patient with multiple medication hypersensitivity reactions.

    Science.gov (United States)

    Jones, Justin M; Richter, Lisa M; Alonto, Augusto; Leedahl, David D

    2015-02-01

    The case of a patient with multiple medication hypersensitivity reactions and a methicillin-resistant Staphylococcus aureus (MRSA) infection who underwent desensitization to ceftaroline is reported. A 32-year-old Caucasian woman with asthma, gastroesophageal reflux disease, heart murmur, and major depression was admitted for MRSA cellulitis with a subcutaneous abscess along the left sternomanubrial joint and clavicular osteomyelitis secondary to port placement after gastric bypass surgery. The patient had an extensive history of hypersensitivity reactions. Pertinent documented allergies were as follows: penicillin (anaphylaxis), daptomycin (anaphylaxis), vancomycin (hives), linezolid (hives), ertapenem (rash), ciprofloxacin (rash), and tigecycline (rash). The patient also reported previous reactions to aztreonam (unknown) and gentamicin (hives). The pharmacy was consulted to develop a desensitization protocol for ceftaroline. The desensitization protocol used three serial dilutions of ceftaroline to make 14 sequential infusions with escalating doses. Intramuscular epinephrine, i.v. diphenhydramine, and i.v. methylprednisolone were ordered as needed for the development of immediate hypersensitivity reactions during or after administration of ceftaroline. The cumulative dose (574.94 mg) was administered intravenously over 225 minutes with no breakthrough symptoms reported during or after the desensitization protocol. Ceftaroline fosamil 600 mg i.v. every 12 hours was continued for six weeks. Desensitization to ceftaroline was conducted for a patient with extensive history of hypersensitivity reactions to other drugs, including penicillin-induced anaphylaxis. Desensitization and subsequent treatment with full doses of ceftaroline were accomplished without apparent adverse effects. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  11. Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons

    Directory of Open Access Journals (Sweden)

    Langeslag Michiel

    2011-12-01

    Full Text Available Abstract Oncostatin M (OSM is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/- and gp130 floxed (gp130fl/fl mice. Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.

  12. Overexpression of the transcription factor NF-YC9 confers abscisic acid hypersensitivity in Arabidopsis.

    Science.gov (United States)

    Bi, Chao; Ma, Yu; Wang, Xiao-Fang; Zhang, Da-Peng

    2017-11-01

    Nuclear factor Y (NF-Y) family proteins are involved in many developmental processes and responses to environmental cues in plants, but whether and how they regulate phytohormone abscisic acid (ABA) signaling need further studies. In the present study, we showed that over-expression of the NF-YC9 gene confers ABA hypersensitivity in both the early seedling growth and stomatal response, while down-regulation of NF-YC9 does not affect ABA response in these processes. We also showed that over-expression of the NF-YC9 gene confers salt and osmotic hypersensitivity in early seedling growth, which is likely to be directly associated with the ABA hypersensitivity. Further, we observed that NF-YC9 physically interacts with the ABA-responsive bZIP transcription factor ABA-INSENSITIVE5 (ABI5), and facilitates the function of ABI5 to bind and activate the promoter of a target gene EM6. Additionally, NF-YC9 up-regulates expression of the ABI5 gene in response to ABA. These findings show that NF-YC9 may be involved in ABA signaling as a positive regulator and likely functions redundantly together with other NF-YC members, and support the model that the NF-YC9 mediates ABA signaling via targeting to and aiding the ABA-responsive transcription factors such as ABI5.

  13. Patch testers' opinions regarding diagnostic criteria for metal hypersensitivity reactions to metallic implants.

    Science.gov (United States)

    Schalock, Peter C; Thyssen, Jacob P

    2013-01-01

    Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated. Diagnostic criteria for hypersensitivity reactions after metallic device implantation are evaluated in this study by a multinational group of patch testers using Thyssen's previously published criteria. A total of 119 dermatologists at the 2012 European Contact Dermatitis Society and 2013 American Contact Dermatitis Society meetings answered a survey regarding their opinions on topics relating to metal hypersensitivity. Four major and 5 minor diagnostic criteria emerged. Approximately 80% of respondents found the following criteria useful (major criteria): chronic dermatitis beginning weeks to months after metallic implantation, eruption overlying the metal implant, positive patch test to a metal component of the implant, and complete clearing after removal of the potentially allergenic implant. Minor criteria (metals (eg, lymphocyte transformation test). In the challenging situation such as a symptomatic or failing orthopedic device, applying these 4 major criteria and the 5 supportive minor criteria may be useful for guiding decision making.

  14. Trichloroethylene Hypersensitivity Syndrome Is Potentially Mediated through Its Metabolite Chloral Hydrate.

    Science.gov (United States)

    Huang, Yongshun; Xia, Lihua; Wu, Qifeng; Zeng, Zifang; Huang, Zhenlie; Zhou, Shanyu; Jin, Jiachun; Huang, Hanlin

    2015-01-01

    We documented previously the entity of trichloroethylene (TCE) hypersensitivity syndrome (THS) in occupational workers. To identify the culprit causative compound, determine the type of hypersensitivity of THS, and establish a screening test for subjects at risk of THS. TCE and its main metabolites chloral hydrate (CH), trichloroethanol (TCOH) and trichloroacetic acid (TCA) were used as allergens at different concentrations in skin patch tests. The study included 19 case subjects diagnosed with occupational THS, 22 control healthy workers exposed to TCE (exposure >12 weeks), and 20 validation new workers exposed to TCE for <12 weeks free of THS. All subjects were followed-up for 12 weeks after the patch test. The highest patch test positive rate in subjects with THS was for CH, followed by TCOH, TCA and TCE. The CH patch test positive rate was 100% irrespective of CH concentrations (15%, 10% and 5%). The TCOH patch test positive rate was concentration-dependent (89.5%, 73.7% and 52.6% for 5%, 0.5% and 0.05%, respectively). Lower patch test positive rates were noted for TCA and TCE. All patch tests (including four allergens) were all negative in each of the 22 control subjects. None of the subjects of the validation group had a positive 15% CH patch test. Chloral hydrate seems to be the culprit causative compound of THS and type IV seems to be the major type of hypersensitivity of THS. The CH patch test could be potentially useful for screening workers at risk of THS.

  15. Management of stinging insect hypersensitivity: a 5-year retrospective medical record review.

    Science.gov (United States)

    Johnson, Thomas; Dietrich, Jeffrey; Hagan, Larry

    2006-08-01

    The Joint Task Force on Practice Parameters for Allergy and Immunology recommends that patients with a history of a systemic reaction to an insect sting be educated on ways to avoid insect stings, carry injectable epinephrine for emergency self-treatment, undergo specific IgE testing for stinging insect sensitivity, and be considered for immunotherapy. To review frontline providers' documented care and recommendations for imported fire ant and flying insect hypersensitivity reactions. A retrospective medical record review was performed of emergency department and primary care clinic visits between November 1, 1999, and November 30, 2004. Using International Classification of Diseases, Ninth Revision, codes, medical records were selected for review to identify patients with potential insect hypersensitivity. A total of 769 medical records from patients who experienced an insect sting were reviewed. Of 120 patients with a systemic reaction, 66 (55.0%) received a prescription for injectable epinephrine, and 14 (11.7%) were given information regarding avoidance of the offending insect. Forty-seven patients with systemic reactions (39.2%) were referred to an allergist. Of 28 patients who kept their appointments and underwent skin testing, 3 had negative results and 25 (89%) had positive results and were advised to start immunotherapy. Adherence to the stinging insect hypersensitivity practice parameter recommendations is poor. Many patients who have experienced a systemic reaction after an insect sting and have sought medical care are not afforded an opportunity for potentially lifesaving therapy.

  16. Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde.

    Science.gov (United States)

    Ridpath, John R; Nakamura, Ayumi; Tano, Keizo; Luke, April M; Sonoda, Eiichiro; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Gillespie, David A F; Sale, Julian E; Yamazoe, Mitsuyoshi; Bishop, Douglas K; Takata, Minoru; Takeda, Shunichi; Watanabe, Masami; Swenberg, James A; Nakamura, Jun

    2007-12-01

    Formaldehyde is an aliphatic monoaldehyde and is a highly reactive environmental human carcinogen. Whereas humans are continuously exposed to exogenous formaldehyde, this reactive aldehyde is a naturally occurring biological compound that is present in human plasma at concentrations ranging from 13 to 97 micromol/L. It has been well documented that DNA-protein crosslinks (DPC) likely play an important role with regard to the genotoxicity and carcinogenicity of formaldehyde. However, little is known about which DNA damage response pathways are essential for cells to counteract formaldehyde. In the present study, we first assessed the DNA damage response to plasma levels of formaldehyde using chicken DT40 cells with targeted mutations in various DNA repair genes. Here, we show that the hypersensitivity to formaldehyde is detected in DT40 mutants deficient in the BRCA/FANC pathway, homologous recombination, or translesion DNA synthesis. In addition, FANCD2-deficient DT40 cells are hypersensitive to acetaldehyde, but not to acrolein, crotonaldehyde, glyoxal, and methylglyoxal. Human cells deficient in FANCC and FANCG are also hypersensitive to plasma levels of formaldehyde. These results indicate that the BRCA/FANC pathway is essential to counteract DPCs caused by aliphatic monoaldehydes. Based on the results obtained in the present study, we are currently proposing that endogenous formaldehyde might have an effect on highly proliferating cells, such as bone marrow cells, as well as an etiology of cancer in Fanconi anemia patients.

  17. Influence of PUVA and UVB radiation on delayed hypersensitivity in the guinea pig

    International Nuclear Information System (INIS)

    Morison, W.L.; Parrish, J.A.; Woehler, M.E.; Krugler, J.I.; Bloch, K.J.

    1981-01-01

    Exposure of guinea pigs to UVA (320--400 nm) radiation following administration of 8-methoxypsoralen by gavage (referred to by the acronym, PUVA) or exposure to UVB (290--320 nm) radiation, produced suppression of the cutaneous delayed hypersensitivity reaction at the site of exposure to radiation and at distant nonexposed sites. In these experiments, the animals were immunized by injection of dinitrophenyl-bovine gamma-globulin (DNP-BGG) in complete Freund's adjuvant and delayed hypersensitivity responses were provoked by intradermal injections of DNP-BGG, DNP and BGG on the flanks. Exposure to erythemogenic doses of either PUVA or UVB radiation for 7 days prior to immunization and for the 7 days between immunization and challenge (total period of radiation: 14 days) produced inhibiton of responses to each of the test substances. In addition, treatment with erythemogenic doses of PUVA either for 7 days prior to immunization or during the interval between immunization and challenge with DNP-BGG, inhibited the delayed hypersensitivity responses at the site of irradiation and at a nonexposed site. These findings suggest that in vivo exposure to nonionizing radiation leads to both local and systemic alteration of certain immune responses

  18. Is Tadpole Pupil in an Adolescent Girl Caused by Denervation Hypersensitivity?

    Science.gov (United States)

    Hansen, Jonas Kjeldbjerg; Møller, Hans Ulrik

    2017-06-01

    Tadpole pupil is a rarely encountered phenomenon caused by episodic, segmental iris dilator muscle spasm of short duration (2-15 minutes), occurring in clusters without a known precipitating factor. It has most commonly been described in women aged 28 to 48 years. A few hypotheses on pathogenesis have been discussed but none has been proved. Here, we present an adolescent girl with bilateral tadpole pupil that appeared during physical exercise. This is the first pediatric case of tadpole pupil, not caused by preceding surgery, to be published. Based on (1) this case in which tadpole pupil developed when the norepinephrine level rose during exercise, (2) the high ratio of patients with tadpole pupil who concurrently have or later develop Horner syndrome, in which denervation hypersensitivity is well described, (3) a previous report of a patient with both tadpole pupil and Horner syndrome who had denervation hypersensitivity on pharmacological testing, (4) a 29-year-old man with unilateral tadpole pupil induced by exercise, and (5) a 19-year-old man with bilateral tadpole pupil and possible autonomic neuropathy, we suggest denervation hypersensitivity as a probable pathogenic mechanism causing tadpole pupil. In addition, a suggestion for investigations to be performed in future pediatric cases is provided. Georg Thieme Verlag KG Stuttgart · New York.

  19. Effects of electroacupuncture on corticotropin-releasing hormone in rats with chronic visceral hypersensitivity.

    Science.gov (United States)

    Liu, Hui-Rong; Fang, Xiao-Yi; Wu, Huan-Gan; Wu, Lu-Yi; Li, Jing; Weng, Zhi-Jun; Guo, Xin-Xin; Li, Yu-Guang

    2015-06-21

    To investigate the effect of electroacupuncture on corticotropin-releasing hormone (CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity. A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7(th) week after the procedure, rats were randomly divided into a model group (MG), electroacupuncture group (EA), and sham electroacupuncture group (S-EA). After treatment, the abdominal withdrawal reflex (AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry (EnVision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and mRNA in the colon, spinal cord, and hypothalamus. The sensitivity of the rats to the colorectal distension stimulus applied at different strengths (20-80 mmHg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased (P 0.05) compared with normal rats (NG). However, the decrease in EA compared with MG rats was statistically significant (P 0.05). Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and mRNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.

  20. Restorative effect of peritoneal macrophages on delayed hypersensitivity following ionizing radiation

    International Nuclear Information System (INIS)

    Volkman, A.; Collins, F.M.

    1971-01-01

    Sublethal whole-body irradiation in the guinea pig had little demonstrable effect on the development of delayed hypersensitivity but caused a profound, though transient depression of dermal reactivity in previously sensitized animals. Macrophage-rich peritoneal cell suspensions from non-sensitive donors when injected intradermally with eliciting antigen, resulted in the restoration of a significant degree of reactivity following irradiation. Inocula of lymphocytes, on the other hand, failed to yield similar results. These findings, when taken with the persistence of low levels of reactivity following irradiation and the ability to transfer reactivity with peritoneal exudate cells from animals so treated, warrant the conclusion that the presence of macrophages is necessary for the expression of cutaneous delayed hypersensitivity. The spontaneously renewed activity which follows the depressed phase is thus more of a reflection of the recovery of macrophage precursors from radiation injury, rather than the emergence of a new population of sensitized cells. The results, in addition, substantiate the belief that the expression of delayed hypersensitivity requires at least two cell populations, only one of which carries the property of specificity at the outset

  1. Prevalence of hypersensitivity to dental local anesthetic drugs in patients referred to Tehran Allergy clinic (2005-2007

    Directory of Open Access Journals (Sweden)

    Akhlaghi F.

    2009-03-01

    Full Text Available "nBackground and Aim: According to controversies in the prevalence of hypersensitivity to dental local anesthetic drugs and patients who claim hypersensitivity to these drugs, the aim of this study was to determine the prevalence of hypersensitivity to dental amide local anesthetic drugs in patients referred to Tehran Allergy Clinic in 2005-2007. "nMaterials and Methods: In this Study (Review of existing data, records of 130 patients who were referred to "Tehran allergy Clinic" (2005-2007 were studied. "nResults: The average age of patients was 29.5±18.8 years. 34% of cases showed positive skin reactions to at least one of the tested Lidocain concentrations and 10% of cases showed positive skin reactions to at least one of the tested Prilocain concentrations. There was a statistically significant difference in hypersensitivity to Lidocain 0.01 and 0.001 (p=0.017 and also between Lidocain 0.001 and 0.0001 (p<0.01. There was no statistically significant difference between other tested drug concentrations (p>0.05. "nConclusion: Many patients with history of hypersensitivity, show positive reaction to local dental anesthetic drugs. Prilocain hypersensitivity reactions are less than Lidocain. So application of Prilocain accompanies with less risk but its application should not be considered completely safe.

  2. Imipramine for Treatment of Esophageal Hypersensitivity and Functional Heartburn: A Randomized Placebo-Controlled Trial.

    Science.gov (United States)

    Limsrivilai, Julajak; Charatcharoenwitthaya, Phunchai; Pausawasdi, Nonthalee; Leelakusolvong, Somchai

    2016-02-01

    Tricyclic antidepressants could be effective in the treatment of symptoms related to hypersensitive esophagus through their pain-modulating effect. We therefore assessed the benefit of imipramine in patients with esophageal hypersensitivity and functional heartburn. Patients with normal endoscopy findings and typical reflux symptoms despite standard-dose proton-pump inhibitor therapy underwent 24-h pH-impedance monitoring. Patients with established esophageal hypersensitivity or functional heartburn were randomly assigned to receive 8 weeks of either once-daily imipramine 25 mg (n=43) or placebo (n=40). The primary end point was satisfactory relief of reflux symptoms, defined as a >50% reduction in the gastroesophageal reflux disease score. The secondary end point was improvement in quality-of-life (QoL) as assessed by the 36-Item Short Form Health Survey score. Patients receiving imipramine did not achieve a higher rate of satisfactory relief of reflux symptoms than did patients receiving placebo (intention-to-treat (ITT) analysis: 37.2 vs. 37.5%, respectively; odds ratio (OR), 0.99; 95% confidence interval (CI), 0.41-2.41; per-protocol (PP) analysis: 45.5 vs. 41.2%, respectively; OR, 1.19; 95% CI, 0.45-3.13). Subgroup analysis to assess the efficacy of imipramine for either esophageal hypersensitivity or functional heartburn yielded similar results. Treatment with imipramine provided significant improvement of QoL by PP analysis (72±17 and 61±19, respectively; P=0.048), but ITT analysis did not reveal any differences between imipramine and placebo (68±19 and 61±19, respectively; P=0.26). Adverse events were similar in both groups; however, constipation was more common with imipramine than placebo (51.2 vs. 22.5%, respectively; P=0.01). Although low-dose imipramine shows potential QoL benefits, it does not relieve symptoms more effectively than does placebo in patients with either esophageal hypersensitivity or functional heartburn.

  3. Plasticity in intact A delta- and C-fibers contributes to cold hypersensitivity in neuropathic rats.

    Science.gov (United States)

    Ji, G; Zhou, S; Kochukov, M Y; Westlund, K N; Carlton, S M

    2007-11-30

    Cold hypersensitivity is a common sensory abnormality accompanying peripheral neuropathies and is difficult to treat. Progress has been made in understanding peripheral mechanisms underlying neuropathic pain but little is known concerning peripheral mechanisms of cold hypersensitivity. The aim of this study was to analyze the contribution of uninjured primary afferents to the cold hypersensitivity that develops in neuropathic rats. Rats with a lumbar 5 (L5) and L6 spinal nerve ligation (SNL, Chung model) but not sham, developed mechanical allodynia, evidenced by decreased paw withdrawal thresholds and increased magnitude of response to von Frey stimulation. Cold hypersensitivity also developed in SNL but not sham rats, evidenced by enhanced nociceptive behaviors induced by placement on a cold plate (6 degrees C) or application of icilin (a transient receptor potential M8 (TRPM8)/transient receptor potential A1 (TRPA1) receptor agonist) to nerve-injured hind paws. Single fiber recordings demonstrated that the mean conduction velocities of intact L4 cutaneous A delta- and C-fibers were not different between naive and SNL rats; however, mechanical thresholds of the A delta- but not the C-fibers were significantly decreased in SNL compared with naive. There was a higher prevalence of C-mechanoheat-cold (CMHC) fibers in SNL compared with naive, but the overall percentage of cold-sensitive C-fibers was not significantly increased compared with naive. This was in contrast to the numerous changes in A delta-fibers: the percentage of L4 cold sensitive A delta-, but not C-fibers, was significantly increased, the percentage of L4 icilin-sensitive A delta-, but not C-fibers, was significantly increased, the icilin-induced activity of L4 A delta-, but not C-fibers, was significantly increased. Icilin-induced activity was blocked by the TRPA1 antagonist Ruthenium Red. The results indicate plasticity in both A delta- and C-uninjured fibers, but A delta fibers appear to provide a

  4. Prescreening based on the presence of CT-scan abnormalities and biomarkers (KL-6 and SP-D may reduce severe radiation pneumonitis after stereotactic radiotherapy

    Directory of Open Access Journals (Sweden)

    Wakui Reiko

    2010-05-01

    Full Text Available Abstract Purpose To determine the risk factors of severe radiation pneumonitis (RP after stereotactic body radiation therapy (SBRT for primary or secondary lung tumors. Materials and methods From January 2003 to March 2009, SBRT was performed on 117 patients (32 patients before 2005 and 85 patients after 2006 with lung tumors (primary = 74 patients and metastatic/recurrent = 43 patients in our institution. In the current study, the results on cases with severe RP (grades 4-5 were evaluated. Serum Krebs von den Lungen-6 (KL-6 and serum Surfactant protein-D (SP-D were used to predict the incidence of RP. A shadow of interstitial pneumonitis (IP on the CT image before performing SBRT was also used as an indicator for RP. Since 2006, patients have been prescreened for biological markers (KL-6 & SP-D as well as checking for an IP-shadow in CT. Results Grades 4-5 RP was observed in nine patients (7.7% after SBRT and seven of these cases (6.0% were grade 5 in our institution. A correlation was found between the incidence of RP and higher serum KL-6 & SP-D levels. IP-shadow in patient's CT was also found to correlate well with the severe RP. Severe RP was reduced from 18.8% before 2005 to 3.5% after 2006 (p = 0.042. There was no correlation between the dose volume histogram parameters and these severe RP patients. Conclusion Patients presenting with an IP shadow in the CT and a high value of the serum KL-6 & SP-D before SBRT treatment developed severe radiation pneumonitis at a high rate. The reduction of RP incidence in patients treated after 2006 may have been attributed to prescreening of the patients. Therefore, pre-screening before SBRT for an IP shadow in CT and serum KL-6 & SP-D is recommended in the management and treatment of patients with primary or secondary lung tumors.

  5. Combinational deletion of three membrane protein-encoding genes highly attenuates yersinia pestis while retaining immunogenicity in a mouse model of pneumonic plague.

    Science.gov (United States)

    Tiner, Bethany L; Sha, Jian; Kirtley, Michelle L; Erova, Tatiana E; Popov, Vsevolod L; Baze, Wallace B; van Lier, Christina J; Ponnusamy, Duraisamy; Andersson, Jourdan A; Motin, Vladimir L; Chauhan, Sadhana; Chopra, Ashok K

    2015-04-01

    Previously, we showed that deletion of genes encoding Braun lipoprotein (Lpp) and MsbB attenuated Yersinia pestis CO92 in mouse and rat models of bubonic and pneumonic plague. While Lpp activates Toll-like receptor 2, the MsbB acyltransferase modifies lipopolysaccharide. Here, we deleted the ail gene (encoding the attachment-invasion locus) from wild-type (WT) strain CO92 or its lpp single and Δlpp ΔmsbB double mutants. While the Δail single mutant was minimally attenuated compared to the WT bacterium in a mouse model of pneumonic plague, the Δlpp Δail double mutant and the Δlpp ΔmsbB Δail triple mutant were increasingly attenuated, with the latter being unable to kill mice at a 50% lethal dose (LD50) equivalent to 6,800 LD50s of WT CO92. The mutant-infected animals developed balanced TH1- and TH2-based immune responses based on antibody isotyping. The triple mutant was cleared from mouse organs rapidly, with concurrent decreases in the production of various cytokines and histopathological lesions. When surviving animals infected with increasing doses of the triple mutant were subsequently challenged on day 24 with the bioluminescent WT CO92 strain (20 to 28 LD50s), 40 to 70% of the mice survived, with efficient clearing of the invading pathogen, as visualized in real time by in vivo imaging. The rapid clearance of the triple mutant, compared to that of WT CO92, from animals was related to the decreased adherence and invasion of human-derived HeLa and A549 alveolar epithelial cells and to its inability to survive intracellularly in these cells as well as in MH-S murine alveolar and primary human macrophages. An early burst of cytokine production in macrophages elicited by the triple mutant compared to WT CO92 and the mutant's sensitivity to the bactericidal effect of human serum would further augment bacterial clearance. Together, deletion of the ail gene from the Δlpp ΔmsbB double mutant severely attenuated Y. pestis CO92 to evoke pneumonic plague in a

  6. Minimizing the source of nociception and its concurrent effect on sensory hypersensitivity: An exploratory study in chronic whiplash patients

    Directory of Open Access Journals (Sweden)

    Stratford Paul

    2010-02-01

    Full Text Available Abstract Background The cervical zygapophyseal joints may be a primary source of pain in up to 60% of individuals with chronic whiplash associated disorders (WAD and may be a contributing factor for peripheral and centrally mediated pain (sensory hypersensitivity. Sensory hypersensitivity has been associated with a poor prognosis. The purpose of the study was to determine if there is a change in measures indicative of sensory hypersensitivity in patients with chronic WAD grade II following a medial branch block (MBB procedure in the cervical spine. Methods Measures of sensory hypersensitivity were taken via quantitative sensory testing (QST consisting of pressure pain thresholds (PPT's and cold pain thresholds (CPT's. In patients with chronic WAD (n = 18, the measures were taken at three sites bilaterally, pre- and post- MBB. Reduced pain thresholds at remote sites have been considered an indicator of central hypersensitivity. A healthy age and gender matched comparison group (n = 18 was measured at baseline. An independent t-test was applied to determine if there were any significant differences between the WAD and normative comparison groups at baseline with respect to cold pain and pressure pain thresholds. A dependent t-test was used to determine whether there were any significant differences between the pre and post intervention cold pain and pressure pain thresholds in the patients with chronic WAD. Results At baseline, PPT's were decreased at all three sites in the WAD group (p Conclusions The patients with chronic WAD showed evidence of widespread sensory hypersensitivity to mechanical and thermal stimuli. The WAD group revealed decreased sensory hypersensitivity following a decrease in their primary source of pain stemming from the cervical zygapophyseal joints.

  7. Minimizing the source of nociception and its concurrent effect on sensory hypersensitivity: an exploratory study in chronic whiplash patients.

    Science.gov (United States)

    Schneider, Geoff M; Smith, Ashley D; Hooper, Allen; Stratford, Paul; Schneider, Kathryn J; Westaway, Michael D; Frizzell, Bevan; Olson, Lee

    2010-02-09

    The cervical zygapophyseal joints may be a primary source of pain in up to 60% of individuals with chronic whiplash associated disorders (WAD) and may be a contributing factor for peripheral and centrally mediated pain (sensory hypersensitivity). Sensory hypersensitivity has been associated with a poor prognosis. The purpose of the study was to determine if there is a change in measures indicative of sensory hypersensitivity in patients with chronic WAD grade II following a medial branch block (MBB) procedure in the cervical spine. Measures of sensory hypersensitivity were taken via quantitative sensory testing (QST) consisting of pressure pain thresholds (PPT's) and cold pain thresholds (CPT's). In patients with chronic WAD (n = 18), the measures were taken at three sites bilaterally, pre- and post- MBB. Reduced pain thresholds at remote sites have been considered an indicator of central hypersensitivity. A healthy age and gender matched comparison group (n = 18) was measured at baseline. An independent t-test was applied to determine if there were any significant differences between the WAD and normative comparison groups at baseline with respect to cold pain and pressure pain thresholds. A dependent t-test was used to determine whether there were any significant differences between the pre and post intervention cold pain and pressure pain thresholds in the patients with chronic WAD. At baseline, PPT's were decreased at all three sites in the WAD group (p < 0.001). Cold pain thresholds were increased in the cervical spine in the WAD group (p < 0.001). Post-MBB, the WAD group showed significant increases in PPT's at all sites (p < 0.05), and significant decreases in CPT's at the cervical spine (p < 0.001). The patients with chronic WAD showed evidence of widespread sensory hypersensitivity to mechanical and thermal stimuli. The WAD group revealed decreased sensory hypersensitivity following a decrease in their primary source of pain stemming from the cervical

  8. Increased mortality by septicemia, interstitial pneumonitis and pulmonary fibrosis among bone marrow transplant recipients receiving an increased mean dose rate of total irradiation

    International Nuclear Information System (INIS)

    Ringden, O.; Baaryd, I.; Johansson, B.

    1983-01-01

    Seven bone marrow transplant recipients with acute lymphoblastic leukemia receiving a mean dose rate of 0.07 Gy/min of total body irradiation towards the pelvic midpoint and the lungs had an increased (p<0.01) overall death rate of 86 per cent compared with 33 per cent among 27 patients with acute non-lymphoblastic leukemia or acute lymphoblastic leukemia treated with a mean dose rate of 0.04 Gy/min. Among the patients receiving the higher dose rate there was an increased mortality in causes related to radiation toxicity like early septicemia, interstitial pneumonitis and pulmonary fibrosis, compared with all patients receiving the lower dose rate (p<0.01) and also with 10 patients from this group with acute lymphoblastic leukemia (p<0.02). (Auth.)

  9. A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.

    Directory of Open Access Journals (Sweden)

    Joel Bozue

    Full Text Available Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

  10. Distribution of the ompA-types among ruminant and swine pneumonic strains of Pasteurella multocida exhibiting various cap-locus and toxA patterns.

    Science.gov (United States)

    Vougidou, C; Sandalakis, V; Psaroulaki, A; Siarkou, V; Petridou, E; Ekateriniadou, L

    2015-05-01

    Pasteurella multocida is an important pathogen in food-producing animals and numerous virulence genes have been identified in an attempt to elucidate the pathogenesis of pasteurellosis. Currently, some of these genes including the capsule biosynthesis genes, the toxA and the OMPs-encoding genes have been suggested as epidemiological markers. However, the number of studies concerning ruminant isolates is limited, while, no attempt has ever been made to investigate the existence of ompA sequence diversity among P. multocida isolates. The aim of the present study was the comparative analysis of 144 P. multocida pneumonic isolates obtained from sheep, goats, cattle and pigs by determining the distribution of the ompA-types in conjunction with the cap-locus and toxA patterns. The ompA genotypes of the isolates were determined using both a PCR-RFLP method and DNA sequence analysis. The most prevalent capsule biosynthesis gene among the isolates was capA (86.1%); a noticeable, however, rate of capD-positive isolates (38.6%) was found among the ovine isolates that had been associated primarily with the capsule type A in the past. Moreover, an unexpectedly high percentage of toxA-positive pneumonic isolates was noticed among small ruminants (93.2% and 85.7% in sheep and goats, respectively), indicating an important epidemiological role of toxigenic P. multocida for these species. Despite their great heterogeneity, certain ompA-genotypes were associated with specific host species, showing evidence of a host preference. The OmpA-based PCR-RFLP method developed proved to be a valuable tool in typing P. multocida strains. Copyright © 2015 Elsevier GmbH. All rights reserved.

  11. Multiple hypersensitivity to mutagens in a cell strain (46BR) derived from a patient with immuno-deficiencies

    International Nuclear Information System (INIS)

    Teo, I.A.; Arlett, C.F.; Harcourt, S.A.; Priestley, A.; Broughton, B.C.

    1983-01-01

    46BR is a fibroblast cell strain established from an individual with hypogammaglobulinaemia. The cells are unique in showing hypersensitivity to the lethal effects of a wide range of DNA-damaging agents. Thus they are hypersensitive to #betta#- and 254-nm UV-irradiation and show a limited capacity to repair potentially lethal #betta#-irradiation damage when compared with fibroblasts from normal individuals. A slight hypersensitivity to mitomycin C was also revealed but we were not able to discriminate 46BR from normals with 4-nitroquinoline oxide. The cells were hypersensitive to the alkylating agents, dimethyl sulphate, methyl methanesulphonate, ethyl methanesulphonate, N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea but not N-ethyl-N-nitrosourea. A consideration of the spectra of DNA lesions produced by these alkylating agents together with the sensitivity to ionising radiation and mitomycin C suggests that 46BR cells are defective in a repair step that is common to all agents. We suggest that the cells are defective in DNA polymerisation or ligation. Support for this suggestion comes from the absence of any hypersensitivity to N-ethyl-N-nitrosourea since its major reaction products are not removed by excision pathways that require polymerisation and ligation. (orig.)

  12. A garlic extract protects from ultraviolet B (280-320 nm) radiation-induced suppression of contact hypersensitivity

    International Nuclear Information System (INIS)

    Reeve, V.E.; Bosnic, M.; Rozinova, E.; Boehm-Wilcox, C.

    1993-01-01

    Lyophilized aged garlic extract has been incorporated at concentrations of 0.1%, 1% and 4% by weight into semi purified powdered diets and fed to hairless mice. Under moderate UVB exposure conditions resulting in 58% suppression of the systemic contact hypersensitivity response in control-fed mice, a dose-responsive protection was observed in the garlic-fed mice; contact hypersensitivity in the UVB-exposed mice fed 4% garlic extract was suppressed by only 19%. If the UVB exposure was replaced by topical application of one of a series of lotions containing increasing concentrations of cis-urocanic acid, a dose-responsive suppression of contact hypersensitivity was demonstrated in control-fed mice (urocanic acid at 25, 50, 100 and 200 micrograms per mouse resulting in 22-46% suppression). Mice fed a diet containing 1% aged garlic extract were partially protected from cis-urocanic acid-induced suppression of contact hypersensitivity, with greater protection from the lower concentrations of urocanic acid. Mice fed a diet containing 4% aged garlic extract were protected from all concentrations of urocanic acid. The results indicate that aged garlic extract contains ingredient(s) that protect from UVB-induced suppression of contact hypersensitivity and suggest that the mechanism of protection is by antagonism of the cis-urocanic acid mediation of this form of immunosuppression

  13. Practical Management of Patients with a History of Immediate Hypersensitivity to Common non-Beta-Lactam Drugs.

    Science.gov (United States)

    Macy, Eric

    2016-01-01

    Immediate hypersensitivity reactions to medications are among the most feared adverse drug reactions, because of their close association with anaphylaxis. This review discusses a practical management approach for patients with a history of an immediate hypersensitivity to a non-beta-lactam medication, where reexposure to the implicated, or similar, medication is clinically necessary. Mechanisms associated with severe immediate hypersensitivity reactions include IgE-mediated mast cell activation, complement-mediated mast cell activation, and direct mast cell activation. Immediate hypersensitivity reactions may also be mediated by vasodilators, other pharmacologic mechanisms, or be secondary to underlying patient-specific biochemical abnormalities such as endocrine tumors or chronic spontaneous urticaria. The key features in the reaction history and the biochemistry of the implicated medication are discussed. Most individuals with a history of immediate hypersensitivity to a medication, who require reuse of that drug, can be safely retreated with a therapeutic course of the implicated drug after a full-dose challenge, graded challenge, or desensitization, with or without premedication and/or any preliminary diagnostic testing, depending on the specific situation.

  14. The preventive effect of resiniferatoxin on the development of cold hypersensitivity induced by spinal nerve ligation: involvement of TRPM8.

    Science.gov (United States)

    Koh, Won Uk; Choi, Seong-Soo; Kim, Ji Hyun; Yoon, Hye Joo; Ahn, Ho-Soo; Lee, Sun Kyung; Leem, Jeong Gil; Song, Jun Gol; Shin, Jin Woo

    2016-06-21

    Resiniferatoxin (RTX) is a potent analog of capsaicin and activates transient receptor potential (TRP) vanilloid type (TRPV) 1. In the current study, we investigated the preventive effect of perineural RTX on the development of cold hypersensitivity induced by spinal nerve ligation (SNL) in rats. Furthermore, we examined the association between the expression level of TRPV1, TRP ankyrin type (TRPA) 1 and TRP melastatin type (TRPM) 8 in the dorsal root ganglion (DRG) and cold hypersensitivity after SNL. RTX pretreatment prevented the development of SNL-induced hypersensitivity to mechanical, thermal, and cold stimuli. Western blot analysis 4 weeks after RTX pretreatment showed that RTX pretreatment decreased the protein expression level of SNL-induced TRPM8, but not TRPV1 or TRPA1, in the DRG of SNL rats. Immunofluorescent analysis revealed that up-regulated TRPM8-stained neurons after SNL co-localized with neurofilament 200-positive neurons located in the DRG. Pretreatment with perineural RTX significantly inhibits SNL-induced mechanical, thermal, and cold hypersensitivity. The antinociceptive effect of perineural RTX, especially on cold hypersensitivity, may be related to the suppression of TRPM8 expression in DRG.

  15. Effectiveness of a baking soda toothpaste delivering calcium and phosphate in reducing dentinal hypersensitivity.

    Science.gov (United States)

    Ghassemi, A; Hooper, W; Winston, A E; Sowinski, J; Bowman, J; Sharma, N

    2009-01-01

    The purpose of this controlled clinical trial was to determine the effectiveness and safety of a single-phase dentifrice that delivers calcium, phosphate, and fluoride to the tooth surface (Arm & Hammer Enamel Care for Sensitive Teeth toothpaste, United Kingdom) in reducing dentinal hypersensitivity. Two-hundred and eight qualifying subjects were randomly assigned to either the Enamel Care dentifrice group or a control dentifrice group, and brushed twice daily with their assigned dentifrice for eight weeks. Pain/discomfort in response to a thermal stimulus was assessed at baseline, week 4, and week 8 using a Visual Analogue Scale (VAS; primary outcome variable) and the Schiff Thermal Sensitivity Scale (STSS; secondary outcome variable). After eight weeks, volunteers from the Enamel Care group were switched to the control dentifrice and participated in a second eight-week study to determine the degree of persistence of pain reduction. Both groups had statistically significant VAS score reductions from baseline at weeks 4 and 8, with mean VAS scores in the Enamel Care group decreasing by 45.6% at week 4 and 61.1% at week 8 (p < 0.0001). Enamel Care was statistically significantly more effective than the control at weeks 4 and 8, with respective mean VAS reductions of 63% (p < 0.0001) and 33% (p = 0.0004) greater than the control. Consistent with the VAS score results, the Enamel Care group had respective statistically significant STSS score reductions of 77% and 58% greater than the control group (p < 0.0001). The reductions in dentinal hypersensitivity seen in the Enamel Care group at week 8 persisted for an additional eight weeks, during which the subjects discontinued use of Enamel Care and brushed with the control dentifrice. Enamel Care for Sensitive Teeth toothpaste (United Kingdom) is an effective dentifrice for the management of dentinal hypersensitivity, and its efficacy persists for a least eight weeks following discontinued product use.

  16. Constructing a classification of hypersensitivity/allergic diseases for ICD-11 by crowdsourcing the allergist community.

    Science.gov (United States)

    Tanno, L K; Calderon, M A; Goldberg, B J; Gayraud, J; Bircher, A J; Casale, T; Li, J; Sanchez-Borges, M; Rosenwasser, L J; Pawankar, R; Papadopoulos, N G; Demoly, P

    2015-06-01

    The global allergy community strongly believes that the 11th revision of the International Classification of Diseases (ICD-11) offers a unique opportunity to improve the classification and coding of hypersensitivity/allergic diseases via inclusion of a specific chapter dedicated to this disease area to facilitate epidemiological studies, as well as to evaluate the true size of the allergy epidemic. In this context, an international collaboration has decided to revise the classification of hypersensitivity/allergic diseases and to validate it for ICD-11 by crowdsourcing the allergist community. After careful comparison between ICD-10 and 11 beta phase linearization codes, we identified gaps and trade-offs allowing us to construct a classification proposal, which was sent to the European Academy of Allergy and Clinical Immunology (EAACI) sections, interest groups, executive committee as well as the World Allergy Organization (WAO), and American Academy of Allergy Asthma and Immunology (AAAAI) leaderships. The crowdsourcing process produced comments from 50 of 171 members contacted by e-mail. The classification proposal has also been discussed at face-to-face meetings with experts of EAACI sections and interest groups and presented in a number of business meetings during the 2014 EAACI annual congress in Copenhagen. As a result, a high-level complex structure of classification for hypersensitivity/allergic diseases has been constructed. The model proposed has been presented to the WHO groups in charge of the ICD revision. The international collaboration of allergy experts appreciates bilateral discussion and aims to get endorsement of their proposals for the final ICD-11. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Cytokine overproduction and crosslinker hypersensitivity are unlinked in Fanconi anemia macrophages.

    Science.gov (United States)

    Garbati, Michael R; Hays, Laura E; Rathbun, R Keaney; Jillette, Nathaniel; Chin, Kathy; Al-Dhalimy, Muhsen; Agarwal, Anupriya; Newell, Amy E Hanlon; Olson, Susan B; Bagby, Grover C

    2016-03-01

    The Fanconi anemia proteins participate in a canonical pathway that repairs cross-linking agent-induced DNA damage. Cells with inactivated Fanconi anemia genes are universally hypersensitive to such agents. Fanconi anemia-deficient hematopoietic stem cells are also hypersensitive to inflammatory cytokines, and, as importantly, Fanconi anemia macrophages overproduce such cytokines in response to TLR4 and TLR7/8 agonists. We questioned whether TLR-induced DNA damage is the primary cause of aberrantly regulated cytokine production in Fanconi anemia macrophages by quantifying TLR agonist-induced TNF-α production, DNA strand breaks, crosslinker-induced chromosomal breakage, and Fanconi anemia core complex function in Fanconi anemia complementation group C-deficient human and murine macrophages. Although both M1 and M2 polarized Fanconi anemia cells were predictably hypersensitive to mitomycin C, only M1 macrophages overproduced TNF-α in response to TLR-activating signals. DNA damaging agents alone did not induce TNF-α production in the absence of TLR agonists in wild-type or Fanconi anemia macrophages, and mitomycin C did not enhance TLR responses in either normal or Fanconi anemia cells. TLR4 and TLR7/8 activation induced cytokine overproduction in Fanconi anemia macrophages. Also, although TLR4 activation was associated with induced double strand breaks, TLR7/8 activation was not. That DNA strand breaks and chromosome breaks are neither necessary nor sufficient to account for the overproduction of inflammatory cytokines by Fanconi anemia cells suggests that noncanonical anti-inflammatory functions of Fanconi anemia complementation group C contribute to the aberrant macrophage phenotype and suggests that suppression of macrophage/TLR hyperreactivity might prevent cytokine-induced stem cell attrition in Fanconi anemia. © Society for Leukocyte Biology.

  18. Trichloroethylene Hypersensitivity Syndrome Is Potentially Mediated through Its Metabolite Chloral Hydrate.

    Directory of Open Access Journals (Sweden)

    Yongshun Huang

    Full Text Available We documented previously the entity of trichloroethylene (TCE hypersensitivity syndrome (THS in occupational workers.To identify the culprit causative compound, determine the type of hypersensitivity of THS, and establish a screening test for subjects at risk of THS.TCE and its main metabolites chloral hydrate (CH, trichloroethanol (TCOH and trichloroacetic acid (TCA were used as allergens at different concentrations in skin patch tests. The study included 19 case subjects diagnosed with occupational THS, 22 control healthy workers exposed to TCE (exposure >12 weeks, and 20 validation new workers exposed to TCE for <12 weeks free of THS. All subjects were followed-up for 12 weeks after the patch test.The highest patch test positive rate in subjects with THS was for CH, followed by TCOH, TCA and TCE. The CH patch test positive rate was 100% irrespective of CH concentrations (15%, 10% and 5%. The TCOH patch test positive rate was concentration-dependent (89.5%, 73.7% and 52.6% for 5%, 0.5% and 0.05%, respectively. Lower patch test positive rates were noted for TCA and TCE. All patch tests (including four allergens were all negative in each of the 22 control subjects. None of the subjects of the validation group had a positive 15% CH patch test.Chloral hydrate seems to be the culprit causative compound of THS and type IV seems to be the major type of hypersensitivity of THS. The CH patch test could be potentially useful for screening workers at risk of THS.

  19. Hypersensitivity reactions to penicillins: studies in a group of patients with negative benzylpenicillin G skin test.

    Science.gov (United States)

    Qiao, H-L; Li, Z; Yang, J; Tian, X; Gao, N; Jia, L-J

    2009-06-01

    Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. The rate of positive reactions for the specific IgE antibodies was 59.40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39.10% (52) and 42.86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7.5%), were significantly fewer than the cross-reacting positive cases (36) to PG (P penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. Radioallergosorbent test is a good complementary test in persons who are skin-test negative with PG, and the sensitivity of RAST increases with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross-reactivity.

  20. Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.

    Science.gov (United States)

    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R; Rago, Carlo; Bhunia, Anil K; Hossain, M Zulfiquer; Paun, Bogdan C; Ren, Yunzhao R; Iacobuzio-Donahue, Christine A; Azad, Nilofer A; Kern, Scott E

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Use of lymphoblastoid cell lines to evaluate the hypersensitivity to ultraviolet radiation in Cockayne syndrome

    International Nuclear Information System (INIS)

    Otsuka, F.; Tarone, R.E.; Cayeux, S.; Robbins, J.H.

    1984-01-01

    Cockayne syndrome (CS) is a rare autosomal recessive disease characterized by acute sun sensitivity, cachectic dwarfism, and neurologic and skeletal abnormalities. Cultured skin fibroblasts from patients with this disease are known to be hypersensitive to the lethal effects of 254-nm UV radiation. The authors have studied the sensitivity of 254-nm UV radiation of lymphoblastoid lines derived from 3 typical CS patients, 1 atypical CS patient who had a very late age of onset of clinical manifestations, 2 patients who had both xeroderma pigmentosum (XP) and typical CS, and 3 heterozygous parents of these patients. Post-UV survival was determined by the trypan-blue dye-exclusion method. The lymphoblastoid lines from the 3 typical CS patients, the atypical CS patient, and the 2 patients with both CS and XP had decreased post-UV viability in comparison with lines from normal donors. Lines from the heterozygous parents had normal post-UV viability. The post-UV viability of the typical CS lines was similar to that of a XP complementation group C line. The relative post-UV viability of lymphoblastoid lines from the typical CS patients was similar to the relative post-UV survival of their fibroblast lines. The lymphoblastoid line from the atypical CS patient had a post-UV viability similar to that of the typical CS patients. Thus, the relative hypersensitivity of CS patients cells in vitro does not reflect the severity or age of onset of the patients clinical manifestations. The lymphoblastoid lines from the 2 patients who had both CS and XP were significantly more sensitive to the UV radiation than those from patients with only CS. Our studies demonstrate that lymphoblastoid lines from patients with CS are appropriate and useful cell lines for the study of the inherited hypersensitivity to UV radiation

  2. Human telomeres are hypersensitive to UV-induced DNA Damage and refractory to repair.

    Directory of Open Access Journals (Sweden)

    Patrick J Rochette

    2010-04-01

    Full Text Available Telomeric repeats preserve genome integrity by stabilizing chromosomes, a function that appears to be important for both cancer and aging. In view of this critical role in genomic integrity, the telomere's own integrity should be of paramount importance to the cell. Ultraviolet light (UV, the preeminent risk factor in skin cancer development, induces mainly cyclobutane pyrimidine dimers (CPD which are both mutagenic and lethal. The human telomeric repeat unit (5'TTAGGG/CCCTAA3' is nearly optimal for acquiring UV-induced CPD, which form at dipyrimidine sites. We developed a ChIP-based technique, immunoprecipitation of DNA damage (IPoD, to simultaneously study DNA damage and repair in the telomere and in the coding regions of p53, 28S rDNA, and mitochondrial DNA. We find that human telomeres in vivo are 7-fold hypersensitive to UV-induced DNA damage. In double-stranded oligonucleotides, this hypersensitivity is a property of both telomeric and non-telomeric repeats; in a series of telomeric repeat oligonucleotides, a phase change conferring UV-sensitivity occurs above 4 repeats. Furthermore, CPD removal in the telomere is almost absent, matching the rate in mitochondria known to lack nucleotide excision repair. Cells containing persistent high levels of telomeric CPDs nevertheless proliferate, and chronic UV irradiation of cells does not accelerate telomere shortening. Telomeres are therefore unique in at least three respects: their biophysical UV sensitivity, their prevention of excision repair, and their tolerance of unrepaired lesions. Utilizing a lesion-tolerance strategy rather than repair would prevent double-strand breaks at closely-opposed excision repair sites on opposite strands of a damage-hypersensitive repeat.

  3. Speech discrimination difficulties in High-Functioning Autism Spectrum Disorder are likely independent of auditory hypersensitivity.

    Directory of Open Access Journals (Sweden)

    William Andrew Dunlop

    2016-08-01

    Full Text Available Autism Spectrum Disorder (ASD, characterised by impaired communication skills and repetitive behaviours, can also result in differences in sensory perception. Individuals with ASD often perform normally in simple auditory tasks but poorly compared to typically developed (TD individuals on complex auditory tasks like discriminating speech from complex background noise. A common trait of individuals with ASD is hypersensitivity to auditory stimulation. No studies to our knowledge consider whether hypersensitivity to sounds is related to differences in speech-in-noise discrimination. We provide novel evidence that individuals with high-functioning ASD show poor performance compared to TD individuals in a speech-in-noise discrimination task with an attentionally demanding background noise, but not in a purely energetic noise. Further, we demonstrate in our small sample that speech-hypersensitivity does not appear to predict performance in the speech-in-noise task. The findings support the argument that an attentional deficit, rather than a perceptual deficit, affects the ability of individuals with ASD to discriminate speech from background noise. Finally, we piloted a novel questionnaire that measures difficulty hearing in noisy environments, and sensitivity to non-verbal and verbal sounds. Psychometric analysis using 128 TD participants provided novel evidence for a difference in sensitivity to non-verbal and verbal sounds, and these findings were reinforced by participants with ASD who also completed the questionnaire. The study was limited by a small and high-functioning sample of participants with ASD. Future work could test larger sample sizes and include lower-functioning ASD participants.

  4. Updating Allergy and/or Hypersensitivity Diagnostic Procedures in the WHO ICD-11 Revision.

    Science.gov (United States)

    Tanno, Luciana Kase; Calderon, Moises A; Li, James; Casale, Thomas; Demoly, Pascal

    2016-01-01

    The classification of allergy and/or hypersensitivity conditions for the World Health Organization (WHO) International Classification of Diseases (ICD)-11 provides the appropriate corresponding codes for allergic diseases, assuming that the final diagnosis is correct. This classification should be linked to in vitro and in vivo diagnostic procedures. Considering the impact for our specialty, we decided to review the codification of these procedures into the ICD aiming to have a baseline and to suggest changes and/or submit new proposals. For that, we prepared a list of the relevant allergy and/or hypersensitivity diagnostic procedures that health care professionals are dealing with on a daily basis. This was based on the main current guidelines and selected all possible and relevant corresponding terms from the ICD-10 (2015 version) and the ICD-11 β phase foundation (June 2015 version). More than 90% of very specific and important diagnostic procedures currently used by the allergists' community on a daily basis are missing. We observed that some concepts usually used by the allergist community on a daily basis are not fully recognized by other specialties. The whole scheme and the correspondence in the ICD-10 (2015 version) and ICD-11 foundation (June 2015 version) provided us a big picture of the missing or imprecise terms and how they are scattered in the current ICD-11 framework, allowing us to submit new proposals to increase the visibility of the allergy and/or hypersensitivity conditions and diagnostic procedures. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  5. Outcomes of premedication for non-ionic radio-contrast media hypersensitivity reactions in Korea

    International Nuclear Information System (INIS)

    Kim, Sae-Hoon; Lee, So-Hee; Lee, Sang-Min; Kang, Hye-Ryun; Park, Heung-Woo; Kim, Sun-Sin; Cho, Sang-Heon

    2011-01-01

    Background: Radio-contrast media (CM)-related adverse reactions are important clinical problems that may cause fatal anaphylaxis. Accordingly, it has been common practice to premedicate patients who have had previous reactions to CM with corticosteroids, antihistamines, and H2 blockers to prevent hypersensitive reactions. However, the effectiveness of premedication has not been properly demonstrated, especially in cases related to non-ionic CM. In this study, we evaluated the effectiveness of premedication at preventing of non-ionic CM immediate-type hypersensitivity reactions. Methods: A total of 30 patients who had been pretreated with corticosteroid and H1 antihistamines and/or H2 blockers in a 3-year period were enrolled. The results of premedication were evaluated in terms of clinical characteristics and the features of breakthrough reactions. Results: Hypersensitivity reactions were not prevented in 5 of the 30 patients who had experienced prior CM reactions (overall recurrence rate after premedication 16.7%; 4/17 patients with mild previous reactions, and 1/13 patients with severe previous reactions). The recurrence rate after premedication was significantly higher in patients with mild previous reactions than in those with severe reactions (23.5% vs. 7.7%; p < 0.001). The breakthrough reactions were similar to the prior reactions in terms of severity and clinical manifestations. Conclusion: Premedication with corticosteroid and H1 antihistamines and/or H2 blockers effectively prevent non-ionic CM-related adverse events in most patients who have had severe previous reactions to CM. However, physicians should be aware of the possibility of premedication failing and of breakthrough reactions, even in cases in which the previous reactions were mild.

  6. Disturbances of motility and visceral hypersensitivity in irritable bowel syndrome: biological markers or epiphenomenon.

    LENUS (Irish Health Repository)

    Quigley, Eamonn M M

    2012-02-03

    Motility and visceral hypersentitivity are regarded as the primary mechanisms of symptom development in irritable bowel syndrome(IBS). While a variety of motor abnormalities have been described throughout the gastrointestinal tract in IBS, their specificity and relationship to symptoms remain unclear. Visceral hypersensitivity is ubiquitous in functional gastrointestinal disease and is especially common in IBS. Again, however, its specificity for IBS has been questioned. Many factors, including stress and psychopathology,complicate the interpretation of these phenomena and new re-search suggests that mucosal inflammation and luminal factors may be more fundamental to the etiology of this common disorder.

  7. Equine allergy therapy: update on the treatment of environmental, insect bite hypersensitivity, and food allergies.

    Science.gov (United States)

    Marsella, Rosanna

    2013-12-01

    Allergies are common in horses. It is important to identify and correct as many factors as possible to control pruritus and make the patient comfortable. Culicoides hypersensitivity is a common component in allergic horses. The main treatment continues to be rigorous fly control and avoidance of insect bites. Environmental allergies are best addressed by early identification of the offending allergens and formulation of allergen-specific immunotherapy to decrease the need for rescue medications. Food allergy is best managed with food avoidance. Urticaria is one of the manifestations of allergic disease wherein detection of the triggering cause is essential for management. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

    DEFF Research Database (Denmark)

    Ostrov, David A; Grant, Barry J; Pompeu, Yuri A

    2012-01-01

    cells, thus causing the equivalent of an alloreactive T-cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir and that were recognized by T cells of hypersensitive patients. The assays that we have established can be applied to test additional...... unclear. Here we show that abacavir can bind within the F pocket of the peptide-binding groove of HLA-B*57:01, thereby altering its specificity. This provides an explanation for HLA-linked idiosyncratic adverse drug reactions, namely that drugs can alter the repertoire of self-peptides presented to T...

  9. Effect of ranitidine on postoperative suppression of natural killer cell activity and delayed hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Pedersen, B K; Moesgaard, F

    1989-01-01

    hypersensitivity (DTH) antigens, and blood drawn immediately before and 24 hours after skin incision was analyzed for spontaneous and in vitro stimulated (IL-2, IFN-alpha or indomethacin) natural killer (NK) cell activity and PHA and PPD-stimulated lymphocyte proliferation. Lymphocyte subsets (helper......-cell activity (p less than 0.02). Postoperative decrease in helper/inducer-T cell numbers was not significantly lessened (p = 0.07), and ranitidine did not influence the levels of suppressor-T cells. PHA and PPD responses in peripheral blood mononuclear cells were unaltered. The results may suggest potential...

  10. Liver dysfunction induced by systemic hypersensitivity reaction to lamotrigine: case report

    Directory of Open Access Journals (Sweden)

    Sung Gyu Im

    2015-06-01

    Full Text Available Lamotrigine is an anticonvulsant drug used to treat partial and generalized seizure disorders. Hypersensitivity to lamotrigine usually causes mild symptoms such as fever, rash, and slight invasion of internal organs. However, a 33-year-old male patient who was admitted with Stevens-Johnson syndrome after taking lamotrigine for 15 days experienced hepatic failure and died 5 days after admission. This case demonstrates the importance of realizing that lamotrigine can lead to fatal hepatic failure, and that tests for the normal liver function should be performed when administering lamotrigine.

  11. The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation

    Directory of Open Access Journals (Sweden)

    Joshua C. Pritchett

    2012-01-01

    Data Sources and Extraction. Drugs identified as causes of (i idiosyncratic reactions, (ii drug-induced hypersensitivity, drug-induced hepatotoxicity, acute liver failure, and Stevens-Johnson syndrome, and (iii human herpes virus reactivation in PubMed since 1997 have been collected and discussed. Results. Data presented in this paper show that HHV-6 reactivation is associated with more severe organ involvement and a prolonged course of disease. Conclusion. This analysis of HHV-6 reactivation associated with drug-induced severe cutaneous reactions and hepatotoxicity will aid in causality assessment and clinical diagnosis of possible life-threatening events and will provide a basis for further patient characterization and therapy.

  12. Epidermal growth factor upregulates serotonin transporter and its association with visceral hypersensitivity in irritable bowel syndrome.

    Science.gov (United States)

    Cui, Xiu-Fang; Zhou, Wei-Mei; Yang, Yan; Zhou, Jun; Li, Xue-Liang; Lin, Lin; Zhang, Hong-Jie

    2014-10-07

    To investigate the role of epidermal growth factor (EGF) in visceral hypersensitivity and its effect on the serotonin transporter (SERT). A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson's correlation analysis. SERT function was examined by tritiated serotonin (5-HT) uptake experiments. Rat intestinal epithelial cells (IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor (EGFR). EGF levels were significantly lower in the rats with visceral hypersensitivity as measured in plasma (2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, P < 0.01) and in colonic tissue (3.244 ± 0.135 ng/100 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P < 0.01) compared with controls. Moreover, the EGF levels were positively correlated with SERT levels (r = 0.820, P < 0.01). EGF displayed dose- and time-dependent increased SERT gene expressions in IEC-6 cells. An EGFR kinase inhibitor inhibited the effect of EGF on SERT gene upregulation. SERT activity was enhanced following treatment with EGF (592.908 ± 31.515 fmol/min per milligram vs 316.789 ± 85.652 fmol/min per milligram protein, P < 0.05) and blocked by the EGFR kinase inhibitor in IEC-6 cells (590.274 ± 25.954 fmol/min per milligram vs 367.834 ± 120.307 fmol/min per milligram protein, P < 0.05). A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT

  13. Hypersensitivity to acid is associated with impaired esophageal mucosal integrity in patients with gastroesophageal reflux disease with and without esophagitis.

    Science.gov (United States)

    Weijenborg, Pim W; Smout, André J P M; Verseijden, Caroline; van Veen, Henk A; Verheij, Joanne; de Jonge, Wouter J; Bredenoord, Albert J

    2014-08-01

    Increased esophageal sensitivity and impaired mucosal integrity have both been described in patients with gastroesophageal reflux disease, but the relationship between hypersensitivity and mucosal integrity is unclear. The aim of the present study was to investigate acid sensitivity in patients with erosive and nonerosive reflux disease and control subjects to determine the relation with functional esophageal mucosal integrity changes as well as to investigate cellular mechanisms of impaired mucosal integrity in these patients. In this prospective experimental study, 12 patients with nonerosive reflux disease, 12 patients with esophagitis grade A or B, and 11 healthy control subjects underwent an acid perfusion test and upper endoscopy. Mucosal integrity was measured during endoscopy by electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance, transepithelial permeability and gene expression of tight junction proteins and filaggrin. Patients with nonerosive reflux disease and esophagitis were more sensitive to acid perfusion compared with control subjects, having a shorter time to perception of heartburn and higher perceived intensity of heartburn. In reflux patients, enhanced acid sensitivity was associated with impairment of in vivo and vitro esophageal mucosal integrity. Mucosal integrity was significantly impaired in patients with esophagitis, displaying higher transepithelial permeability and lower extracellular impedance. Although no significant differences in the expression of tight junction proteins were found in biopsies among patient groups, mucosal integrity parameters in reflux patients correlated negatively with the expression of filaggrin. In conclusion, sensitivity to acid is enhanced in patients with gastroesophageal reflux disease, irrespective of the presence of erosions, and is associated with impaired esophageal mucosal integrity. Mucosal integrity of the esophagus

  14. Type IV Hypersensitivity to Gold Weight Upper-Eyelid Implant: Case Report and Review of the Literature.

    Science.gov (United States)

    Kilduff, Caroline L S; Casswell, Edward J; Imonikhe, Richard; Marjanovic, Branka

    2017-05-04

    Complications associated with gold-weight insertion for lagophthalmos are uncommon, recent reports have provided evidence to suggest that type IV hypersensitivity to gold can cause a persistent inflammatory reaction. We present a case of a 46-year-old man who experienced persistent post-operative inflammation, and summarize previously documented cases. This patient underwent uncomplicated insertion of an upper eyelid gold weight for right-sided facial nerve palsy. He had no allergies or implanted metalwork. Post-operatively erythema was noted at seven-weeks and did not resolve. The weight was removed after six-months. The histopathological findings were in keeping with type IV hypersensitivity and similar to previous cases. Although infrequent, this complication has poor outcomes. The definitive management is removal of the weight. Information regarding implanted gold, and previous reactions should be elicited pre-operatively. Type IV hypersensitivity should be considered in patients with persistent inflammation that do not respond to antibiotic or steroid therapy.

  15. Pneumonia de hipersensibilidade crônica: análise de oito casos e revisão da literatura Chronic hypersensitivity pneumonia: analysis of eight cases and review of the literature

    Directory of Open Access Journals (Sweden)

    MARIA DE FATIMA DO AMPARO TEIXEIRA

    2002-06-01

    Full Text Available A pneumonia de hipersensibilidade é uma doença de natureza imunológica secundária à ina