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Sample records for hypersensitivity avaliacao clinica

  1. Hypersensitivity Pneumonitis

    MedlinePlus

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

  2. Drug hypersensitivity.

    PubMed

    Yawalkar, N

    2009-01-01

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

  3. Hypersensitivity pneumonitis

    MedlinePlus

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

  4. Copper hypersensitivity.

    PubMed

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

    2014-10-01

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

  5. An evening at "La Clinica del Pueblo".

    PubMed

    Shefsky, M L

    1986-01-01

    This article describes a typical evening at the Clinica del Pueblo in the Hispanic neighborhood of Adams-Morgan in Washington, D.c. The Clinical del Pueblo began operating in 1983 in response to the urgen medical needs of Central American refugees arriving in the Washington D.c. area. The refugees bring with them severe trauma, fear, and health problems caused by the civil was and exacerbated by inadequate or non-existant health services. Approximately 80,000 Salvadoran refugees live in the area. They do not receive adequate health care for 3 reasons. 1) Because the US goverment is unwilling to recognize them as true refugees, they live with the constant threat of deportatin back to the violence from which they have fled. 2) Refugees lack the ability to pay for private care. 3) Langauage and culture create frightening barriers to health care for the refugees. For those who do seek care, these barriers can lead to the inadequate or incomplete diagnoses and poor compliance and follow-up. Plenty International and the Central American Refugee Center responded to these problems by organizing a free clinic to provide not only medical care but also a training course for volunteers. The director of the clinic organizes the course, the classes are taught by a variety of people including the clinic's volunteer physicians, nurses, and public health educators as well as graduates of previus training courses and people from the wider community. The services of the clinic reach only a small portion of the population in need. However, the fact that free medical services are now available to some Central American refugees make the Clinica del Pueblo an important program.

  6. Oral Hypersensitivity Reactions

    MedlinePlus

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

  7. Drug hypersensitivity syndrome.

    PubMed

    Bonnetblanc, J M

    1993-01-01

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

  8. The first century of the "clinica del lavoro" in Milan.

    PubMed

    Bertazzi, Pier Alberto; Foà, Vito

    2005-01-01

    The Clinica del Lavoro was created in Milan at the beginning of the 20th century by Luigi Devotto, who deemed it essential for physicians and health researchers to get involved in the life and health problems of working populations. The main roles of the Clinica del Lavoro were to educate medical students and train physicians; study actual workplaces, examine health and safety hazards and their noxious effects; and create initiatives and services to protect and promote workers' health. Important scientific contributions were made in several fields, including chemical carcinogenesis, effects of mineral and biologicalfibers, mechanism of action of silica dust, methods for the detection and measurements of toxic substances in both the work environment and workers' biological media.

  9. Pharmacogenetics of drug hypersensitivity

    PubMed Central

    Phillips, Elizabeth J; Mallal, Simon A

    2010-01-01

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

  10. [Food hypersensitivity in children].

    PubMed

    Kolacek, Sanja

    2011-01-01

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

  11. Management Strategies for Clopidogrel Hypersensitivity.

    PubMed

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

    2015-06-01

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

  12. Laryngeal hypersensitivity in chronic cough.

    PubMed

    Hull, J H; Menon, A

    2015-12-01

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

  13. Chronic hypersensitivity pneumonitis

    PubMed Central

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

    2016-01-01

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

  14. Insect and arachnid hypersensitivity.

    PubMed

    Bevier, D E

    1999-11-01

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

  15. Hypersensitivity reactions to fluoroquinolones.

    PubMed

    Scherer, Kathrin; Bircher, Andreas J

    2005-01-01

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

  16. Food hypersensitivity by inhalation

    PubMed Central

    Ramirez, Daniel A; Bahna, Sami L

    2009-01-01

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

  17. Acta Clinica Croatica: progress of a journal step by step.

    PubMed

    Ramljak, Gordana

    2014-03-01

    The journal Acta Clinica Croatica (ACC) was founded in 1962 under the title Anali Bolnice Dr. M. Stojanović. In 1995, the title of the journal was changed into its present form and ever since all papers have been published in English. In 2000, the electronic (online) edition of the ACC was released in addition to the print version. The paper presents development of the journal from 1962 to 2012 based on the analysis of the following SCOPUS citation index parameters: type and number of documents published in the journal; number of citations; and number of domestic and foreign authors. The studied period was analyzed in three time segments: the period from 1995 to 1999, the period from 2000 to 2006 and the period from 2007 to 2012. The same parameters were analyzed in the Web of Science/SCI-Expanded bibliographic and citation index for the 2007-2012 period. The increasing number of documents, authors (both domestic and foreign) and citations demonstrates gradual rise in the quality, visibility and impact of the journal. The fifty years of experience show that a goal, at first very distant and almost unachievable, may be reached by progressing step by step.

  18. Jaundice induced by stanozolol hypersensitivity

    PubMed Central

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

    1976-01-01

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

  19. Hypersensitivity to antineoplastic agents.

    PubMed

    Castells, M C

    2008-01-01

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

  20. Hypersensitivity to fluoroquinolones

    PubMed Central

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

    2016-01-01

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

  1. Immunological Mechanisms of Drug Hypersensitivity.

    PubMed

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

    2016-01-01

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

  2. Cockroach hypersensitivity in asthmatic patients.

    PubMed

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

    1988-01-01

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

  3. OC ToGo: bed site image integration into OpenClinica with mobile devices

    NASA Astrophysics Data System (ADS)

    Haak, Daniel; Gehlen, Johan; Jonas, Stephan; Deserno, Thomas M.

    2014-03-01

    Imaging and image-based measurements nowadays play an essential role in controlled clinical trials, but electronic data capture (EDC) systems insufficiently support integration of captured images by mobile devices (e.g. smartphones and tablets). The web application OpenClinica has established as one of the world's leading EDC systems and is used to collect, manage and store data of clinical trials in electronic case report forms (eCRFs). In this paper, we present a mobile application for instantaneous integration of images into OpenClinica directly during examination on patient's bed site. The communication between the Android application and OpenClinica is based on the simple object access protocol (SOAP) and representational state transfer (REST) web services for metadata, and secure file transfer protocol (SFTP) for image transfer, respectively. OpenClinica's web services are used to query context information (e.g. existing studies, events and subjects) and to import data into the eCRF, as well as export of eCRF metadata and structural information. A stable image transfer is ensured and progress information (e.g. remaining time) visualized to the user. The workflow is demonstrated for a European multi-center registry, where patients with calciphylaxis disease are included. Our approach improves the EDC workflow, saves time, and reduces costs. Furthermore, data privacy is enhanced, since storage of private health data on the imaging devices becomes obsolete.

  4. [The role of the "Clinica del Lavoro Luigi Devoto" in international research].

    PubMed

    Bertazzi, P A; Forni, Alessandra M

    2003-01-01

    During its long history, the Clinica del Lavoro Luigi Devoto has produced numerous internationally recognized scientific contributions in the specific field of occupational medicine and health, and in other broader areas as, for example, immunology, toxicology, cytogenetics. Pivotal in this activity was the figure of Enrico C. Vigliani, director of the Clinica for over 35 years. We mention here, in particular, the results of the study of "early" markers of lead intoxication; the research on the carcinogenicity of benzene and aromatic amines; the study of the pathogenesis of silicosis and byssinosis; the study of cytogenetic damage after exposure to industrial toxic chemicals; the technical research for dust abatement in mines. Such research also played a major role in the development of pulmonary medicine, toxicology and immunology in Italy, and conferred scientific dignity on the newborn "industrial hygiene" discipline thanks to the work of Nicola Zurlo. Today, the Clinica's research is maintained at international standards especially by the work of thematic Research Centers recently established within the Clinica, covering fields such as occupational and environmental toxicology, occupational oncology, ergonomics, respiratory disease and allergy, psycho-social risk factors. These Centers are also devoted to the development of innovative methods in epidemiology, toxicology, psychology, molecular biology, and ergonomic measurement for the identification and evaluation of health risks at work.

  5. Drug hypersensitivity reactions involving skin.

    PubMed

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

    2010-01-01

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

  6. Central hypersensitivity in chronic musculoskeletal pain.

    PubMed

    Curatolo, Michele; Arendt-Nielsen, Lars

    2015-05-01

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

  7. Ibuprofen-induced hypersensitivity syndrome.

    PubMed

    Nanau, Radu M; Neuman, Manuela G

    2010-06-01

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

  8. Genotyping for Severe Drug Hypersensitivity

    PubMed Central

    Karlin, Eric; Phillips, Elizabeth

    2014-01-01

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

  9. Reaginic hypersensitivity in ulcerative colitis

    PubMed Central

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

    1972-01-01

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

  10. Cytomegalovirus reactivation in drug induced hypersensitivity syndrome.

    PubMed

    Mathuram, Alice J; George, Renu E

    2014-06-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2005-01-01

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

  13. Clinical heterogeneity of drug hypersensitivity.

    PubMed

    Roujeau, Jean-Claude

    2005-04-15

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

  14. Hypothesis on how to measure electromagnetic hypersensitivity.

    PubMed

    Tuengler, Andreas; von Klitzing, Lebrecht

    2013-09-01

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

  15. Hypersensitivity to contrast media and dyes.

    PubMed

    Brockow, Knut; Sánchez-Borges, Mario

    2014-08-01

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

  16. Sympathoinhibition and hypotension in carotid sinus hypersensitivity

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  17. Drug-Hypersensitivity Syndrome: Diagnosis and Treatment

    PubMed Central

    Hamm, Rose L.

    2012-01-01

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

  18. Esophageal hypersensitivity in noncardiac chest pain.

    PubMed

    Min, Yang Won; Rhee, Poong-Lyul

    2016-09-01

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

  19. Hypersensitivity reactions to dapsone: a systematic review.

    PubMed

    Lorenz, Maria; Wozel, Gottfried; Schmitt, Jochen

    2012-03-01

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

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

    PubMed

    Vickers, Kristin

    2012-05-15

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

  1. TRPA1 Contributes to Cold Hypersensitivity

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  3. Delayed cutaneous manifestations of drug hypersensitivity.

    PubMed

    Bircher, Andreas J; Scherer, Kathrin

    2010-07-01

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

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

    PubMed

    Burke, Michael J

    2014-12-01

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

  5. Severe Hyperacusis, Photophobia, and Skin Hypersensitivity

    PubMed Central

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

    2016-01-01

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

  6. Metal Hypersensitivity and Total Knee Arthroplasty.

    PubMed

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

    2016-02-01

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

  7. Immediate-type hypersensitivity drug reactions

    PubMed Central

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

    2014-01-01

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

  8. Anticonvulsant hypersensitivity syndrome secondary to carbamazepine

    PubMed Central

    Brown, Shannon C.

    2017-01-01

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

  9. Metal Hypersensitivity and Total Knee Arthroplasty

    PubMed Central

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

    2015-01-01

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

  10. Hydrocodone snorting leading to hypersensitivity pneumonitis

    PubMed Central

    Vijayaraghavan, Vimala

    2016-01-01

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

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

    PubMed

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

    1999-12-01

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

  12. Treatments for hypersensitive noncarious cervical lesions

    PubMed Central

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

    2014-01-01

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

  13. An unexpected positive hypersensitive reaction to eugenol.

    PubMed

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

    2013-09-18

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

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

    PubMed

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

    1997-01-01

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

  15. Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria

    PubMed Central

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

    2005-01-01

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

  16. Hypersensitivity pneumonitis due to an ultrasonic humidifier.

    PubMed

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

    1998-02-01

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

  17. Phenytoin-induced acute hypersensitivity pneumonitis.

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2014-07-07

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

  19. Drug hypersensitivity: pharmacogenetics and clinical syndromes.

    PubMed

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

    2011-03-01

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

  20. TRPA1 contributes to cold hypersensitivity.

    PubMed

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

    2010-11-10

    TRPA1 is a nonselective cation channel expressed by nociceptors. Although it is widely accepted that TRPA1 serves as a broad irritancy receptor for a variety of reactive chemicals, its role in cold sensation remains controversial. Here, we demonstrate that mild cooling markedly increases agonist-evoked rat TRPA1 currents. In the absence of an agonist, even noxious cold only increases current amplitude slightly. These results suggest that TRPA1 is a key mediator of cold hypersensitivity in pathological conditions in which reactive oxygen species and proinflammatory activators of the channel are present, but likely plays a comparatively minor role in acute cold sensation. Supporting this, cold hypersensitivity can be induced in wild-type but not Trpa1(-/-) mice by subcutaneous administration of a TRPA1 agonist. Furthermore, the selective TRPA1 antagonist HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide] reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain.

  1. Drug Hypersensitivity: Pharmacogenetics and Clinical Syndromes

    PubMed Central

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

    2011-01-01

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

  2. Stent hypersensitivity and infection in sinus cavities

    PubMed Central

    Soufras, George D.; Hahalis, George

    2013-01-01

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

  3. Delayed drug hypersensitivity reactions - new concepts.

    PubMed

    Posadas, S J; Pichler, W J

    2007-07-01

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

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

    PubMed

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

    2004-07-01

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

  5. A physiologic differentiation between delayed and immediate hypersensitivity

    PubMed Central

    Apicella, Michael A.; Allen, James C.

    1969-01-01

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

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

    PubMed

    Otani, Iris M; Banerji, Aleena

    2016-03-01

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

  7. X-ray induction of persistent hypersensitivity to mutation

    SciTech Connect

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

    1982-04-16

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

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

    PubMed

    Zhou, QiQi; Verne, G Nicholas

    2011-06-01

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

  9. Two factors responsible for the development of denervation hypersensitivity

    PubMed Central

    Jones, Rosemary; Vrbová, Gerta

    1974-01-01

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

  10. Lymphocyte transformation studies in drug hypersensitivity

    PubMed Central

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

    1979-01-01

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

  11. LLLT in treating dentinary hypersensitivity: new concepts

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

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

  12. Use of contact hypersensitivity in immunotoxicity testing.

    PubMed

    Descotes, Jacques

    2010-01-01

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

  13. Lymphocyte transformation studies in drug hypersensitivity.

    PubMed

    Warrington, R J; Tse, K S

    1979-05-05

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

  14. Management of nonimmediate hypersensitivity reactions to drugs.

    PubMed

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

    2014-08-01

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

  15. Acute eosinophilic pneumonia: a hypersensitivity phenomenon?

    PubMed

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

    1989-01-01

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

  16. Hypersensitivity and nanoparticles: update and research trends

    PubMed Central

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

    2016-01-01

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

  17. Automated Import of Clinical Data from HL7 Messages into OpenClinica and tranSMART Using Mirth Connect.

    PubMed

    Camacho Rodriguez, Juan Carlos; Stäubert, Sebastian; Löbe, Matthias

    2016-01-01

    Electronic data capture (EDC) tools are designed to simplify data acquisition, improving data quality and managing clinical data electronically. Some data are collected from the laboratory information management system (LIMS), which is an important data source for a study. OpenClinica is an open source clinical data management system (CDMS) for web-based electronic data capture (EDC), which is used widely in academic clinical research. TranSMART is also an open source web-based platform used for the management and analysis of different data types common in clinical and translational research. Many LIMS use the Health Level 7 standard - Version 2.x (HL7) as a message exchange protocol. In this paper, we implement Mirth Connect as a Communication Server (CS) to convert these HL7 messages either to Operational Data Model (ODM) data for the automatic import in OpenClinica or tabular-delimited text format files, whose data is uploaded in tranSMART using the tMDataLoader tool.

  18. Occupational hypersensitivity pneumonitis: an EAACI position paper.

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    1976-01-01

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

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  2. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  3. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  4. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  5. Stress induces transient auditory hypersensitivity in rats.

    PubMed

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

    2010-01-01

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

  6. Non-surgical management of tooth hypersensitivity.

    PubMed

    Clark, Danielle; Levin, Liran

    2016-10-01

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

  7. Hypersensitivity to ticks and Lyme disease risk.

    PubMed

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

    2005-01-01

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

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

    PubMed Central

    Ajwani, Sanil Harji; Charalambous, Charalambos P.

    2016-01-01

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

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

    PubMed

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

    2012-07-01

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

  10. Low Ubiquinone Content in Escherichia coli Causes Thiol Hypersensitivity

    PubMed Central

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

    1998-01-01

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

  11. Effectiveness of Lasers in the Treatment of Dentin Hypersensitivity

    PubMed Central

    Asnaashari, Mohammad; Moeini, Masoumeh

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2009-12-01

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

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

    EPA Pesticide Factsheets

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

  15. Dentin hypersensitivity: Recent trends in management

    PubMed Central

    Miglani, Sanjay; Aggarwal, Vivek; Ahuja, Bhoomika

    2010-01-01

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

  16. Immediate and delayed type hypersensitivity to malathion.

    PubMed

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

    1992-12-01

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

  17. Hypersensitivity pneumonitis associated with home ultrasonic humidifiers.

    PubMed

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

    1995-03-01

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

  18. IgE-mediated food hypersensitivity disorders.

    PubMed

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

    2008-04-01

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

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

    PubMed

    Garvey, Lene Heise

    2016-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  1. [Pathogenesis and treatment of hypersensitivity pneumonitis].

    PubMed

    Ando, M

    2000-01-01

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

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

    PubMed

    Victor, J B; Halverson, C F

    1975-01-01

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

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

    PubMed

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

    2015-12-01

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

  4. Hypersensitivity to thrombin of platelets from hypercholesterolemic rats

    SciTech Connect

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

    1986-03-01

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

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

    PubMed Central

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

    1975-01-01

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

  6. Effect of premedications in a murine model of asparaginase hypersensitivity.

    PubMed

    Fernandez, Christian A; Smith, Colton; Karol, Seth E; Ramsey, Laura B; Liu, Chengcheng; Pui, Ching-Hon; Jeha, Sima; Evans, William E; Finkelman, Fred D; Relling, Mary V

    2015-03-01

    A murine model was developed that recapitulates key features of clinical hypersensitivity to Escherichia coli asparaginase. Sensitized mice developed high levels of anti-asparaginase IgG antibodies and had immediate hypersensitivity reactions to asparaginase upon challenge. Sensitized mice had complete inhibition of plasma asparaginase activity (P = 4.2 × 10(-13)) and elevated levels of mouse mast cell protease 1 (P = 6.1 × 10(-3)) compared with nonsensitized mice. We investigated the influence of pretreatment with triprolidine, cimetidine, the platelet activating factor (PAF) receptor antagonist CV-6209 [2-(2-acetyl-6-methoxy-3,9-dioxo-4,8-dioxa-2,10-diazaoctacos-1-yl)-1-ethyl-pyridinium chloride], or dexamethasone on the severity of asparaginase-induced allergies. Combining triprolidine and CV-6209 was best for mitigating asparaginase-induced hypersensitivity compared with nonpretreated, sensitized mice (P = 1.2 × 10(-5)). However, pretreatment with oral dexamethasone was the only agent capable of mitigating the severity of the hypersensitivity (P = 0.03) and partially restoring asparaginase activity (P = 8.3 × 10(-4)). To rescue asparaginase activity in sensitized mice without requiring dexamethasone, a 5-fold greater dose of asparaginase was needed to restore enzyme activity to a similar concentration as in nonsensitized mice. Our results suggest a role of histamine and PAF in asparaginase-induced allergies and indicate that mast cell-derived proteases released during asparaginase allergy may be a useful marker of clinical hypersensitivity.

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

    PubMed

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

    2008-10-01

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

  8. Hypersensitivity to proton pump inhibitors: lansoprazole-induced Kounis syndrome.

    PubMed

    Vlahos, Nicholas P; Vavilis, George K; Giannelou, Ageliki G; Georgopoulou, Christina N; Kommata, Varvara J; Kougias, Constantinos T; Tsartsalis, Dimitrios N; Kounis, George N; Mazarakis, Andreas; Batsolaki, Maria; Gouvelou-Deligianni, Geogia V; Hahalis, George; Kounis, Nicholas G

    2009-05-29

    Proton pump inhibitors are commonly used in clinical practice for the treatment of peptic ulcer and gastroesophageal reflux and are well tolerated by the patients. Their use is rarely associated with hypersensitivity and anaphylactic reactions. According to the reports in the Uppsala Monitoring Center database the frequency of hypersensitivity reactions out of all reported adverse reactions for proton pump inhibitors and H2-histamine receptor antagonists was between 0.2% and 0.7%. A few cases of hypersensitivity to lansoprazole have been reported. We report a patient who developed Kounis syndrome after taking 30 mg of lansoprazole. This is the first report of Kounis syndrome associated with lansoprazole administration in the world literature.

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

    PubMed Central

    Davari, AR; Ataei, E; Assarzadeh, H

    2013-01-01

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

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

    PubMed Central

    Balla, Sudarshan; Aggarwal, Kul

    2016-01-01

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

  11. Contact hypersensitivity response to isophorone diisocyanate in mice

    SciTech Connect

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

    1989-09-01

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

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

    PubMed

    Keohane, John; Quigley, Eamonn M M

    2006-05-07

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

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

    PubMed

    Remes-Troche, Jose M

    2010-10-01

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

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

    PubMed

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

    2010-01-01

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

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

    PubMed

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

    2012-01-25

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

  16. Virtual-reality-based attention assessment of ADHD: ClinicaVR: Classroom-CPT versus a traditional continuous performance test.

    PubMed

    Neguț, Alexandra; Jurma, Anda Maria; David, Daniel

    2016-06-03

    Virtual-reality-based assessment may be a good alternative to classical or computerized neuropsychological assessment due to increased ecological validity. ClinicaVR: Classroom-CPT (VC) is a neuropsychological test embedded in virtual reality that is designed to assess attention deficits in children with attention deficit hyperactivity disorder (ADHD) or other conditions associated with impaired attention. The present study aimed to (1) investigate the diagnostic validity of VC in comparison to a traditional continuous performance test (CPT), (2) explore the task difficulty of VC, (3) address the effect of distractors on the performance of ADHD participants and typically-developing (TD) controls, and (4) compare the two measures on cognitive absorption. A total of 33 children diagnosed with ADHD and 42 TD children, aged between 7 and 13 years, participated in the study and were tested with a traditional CPT or with VC, along with several cognitive measures and an adapted version of the Cognitive Absorption Scale. A mixed multivariate analysis of covariance (MANCOVA) revealed that the children with ADHD performed worse on correct responses had more commissions and omissions errors than the TD children, as well as slower target reaction times . The results showed significant differences between performance in the virtual environment and the traditional computerized one, with longer reaction times in virtual reality. The data analysis highlighted the negative influence of auditory distractors on attention performance in the case of the children with ADHD, but not for the TD children. Finally, the two measures did not differ on the cognitive absorption perceived by the children.

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

    PubMed

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

    2012-01-01

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

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

    PubMed

    Potiwat, Rutcharin; Sitcharungsi, Raweerat

    2015-12-01

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

  19. Delayed-type hypersensitivity reaction against Nexplanon®.

    PubMed

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

    2015-01-01

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

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

    PubMed

    Shlyakhov, E; Rubinstein, E

    1994-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  2. Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood

    PubMed Central

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

    2017-01-01

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

  3. Estrogen-dependent visceral hypersensitivity following stress in rats

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Otani, Iris M; Banerji, Aleena

    2016-03-01

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

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

    PubMed

    Todd, Sej; Emerson, C R

    2017-03-01

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

  6. Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions

    PubMed Central

    Böhm, Ruwen; Cascorbi, Ingolf

    2016-01-01

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

  7. Hypersensitivity with Inhalational Budesonide: An Under Recognised Entity

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    De Almeida, F A; Croce, J

    1990-01-01

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

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

    PubMed

    Venter, Carina

    2009-01-01

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

  11. Hypersensitive reaction to praziquantel in a clonorchiasis patient.

    PubMed

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

    2011-09-01

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

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

    PubMed Central

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

    1988-01-01

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

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

    PubMed

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

    2013-02-01

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

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

    PubMed

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

    2017-02-01

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

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

    PubMed Central

    Zakrzewski, Aleksander; Matuszewski, Tomasz; Kruszewski, Jerzy

    2013-01-01

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

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

    SciTech Connect

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

    1992-03-01

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

  17. Carbimazole-associated hypersensitivity vasculitis in a cat.

    PubMed

    Bowlt, K; Cattin, I; Stewart, J

    2014-12-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

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

  20. Genome-wide analysis links NFATC2 with asparaginase hypersensitivity

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    1996-01-01

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

  2. Immediate hypersensitivity reactions to penicillins and other betalactams.

    PubMed

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

    2006-01-01

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

  3. Type I hypersensitivity reaction as a complication of lepa

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Lena, Karlsson; Marianne, Kjaeldgaard

    2017-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2017-01-25

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

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

    PubMed Central

    Dai, Jing; Ge, Changjiang

    2017-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Zhou, QiQi; Verne, G. Nicholas

    2012-01-01

    A subset of patients with IBS have visceral hypersensitivity and/or somatic hypersensitivity. Visceral hypersensitivity might have use as a clinical marker of IBS and could account for symptoms of urgency for bowel movements, bloating and abdominal pain. The mechanisms that lead to chronic visceral hypersensitivity in patients who have IBS are unclear. However, several working models may be considered, including: nociceptive input from the colon that leads to hypersensitivity; increased intestinal permeability that induces a visceral nociceptive drive; and alterations in the expression of microRNAs in gastrointestinal tissue that might be delivered via blood microvesicles to other target organs, such as the peripheral and/or central nervous system. As such, the chronic visceral hypersensitivity that is present in a subset of patients with IBS might be maintained by both peripheral and central phenomena. The theories underlying the development of chronic visceral hypersensitivity in patients with IBS are supported by findings from new animal models in which hypersensitivity follows transient inflammation of the colon. The presence of somatic hypersensitivity and an alteration in the neuroendocrine system in some patients who have IBS suggests that multisystemic factors are involved in the overall disorder. Thus, IBS is similar to other chronic pain disorders, such as fibromyalgia, chronic regional pain disorder and temporomandibular joint disorder, as chronic nociceptive mechanisms are activated in all of these disorders. PMID:21643039

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-02-01

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

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

    PubMed

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

    2016-01-01

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

  14. Hypersensitivity of excitation-contraction coupling in dystrophic cardiomyocytes

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed

    Zacharisen, Michael C; Fink, Jordan N

    2011-11-01

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

  17. Unusual formaldehyde-induced hypersensitivity in two schoolgirls

    SciTech Connect

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

    1990-01-01

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

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

    PubMed

    Tohyama, Mikiko; Hashimoto, Koji

    2009-06-01

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

  19. Electromagnetic hypersensitivity: The opinion of an observer neurologist

    NASA Astrophysics Data System (ADS)

    Marc-Vergnes, Jean-Pierre

    2010-11-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2011-05-01

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

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

    PubMed

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

    1998-07-01

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

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

    PubMed Central

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

    2016-01-01

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

  4. A Case of Occupational Hypersensitivity Pneumonitis Associated with Trichloroethylene

    PubMed Central

    Kim, Young Jae; Hwang, Eu Dong; Leem, Ah Young; Kang, Beo Deul; Chang, Soo Yun; Kim, Ho Keun; Park, In Kyu; Kim, Song Yee; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Park, Moo Suk; Kim, Young Sam; Kim, Se Kyu; Chang, Joon

    2014-01-01

    Trichloroethylene (TCE) is a toxic chemical commonly used as a degreasing agent, and it is usually found in a colorless or blue liquid form. TCE has a sweet, chloroform-like odor, and this volatile chlorinated organic chemical can cause toxic hepatitis, neurophysiological disorders, skin disorders, and hypersensitivity syndromes. However, the hypersensitivity pneumonitis (HP) attributed to TCE has rarely been reported. We hereby describe a case of HP associated with TCE in a 29-year-old man who was employed as a lead welder at a computer repair center. He was installing the capacitors on computer chip boards and had been wiped down with TCE. He was admitted to our hospital with complaints of dry coughs, night sweats, and weight losses for the past two months. HP due to TCE exposure was being suspected due to his occupational history, and the results of a video-associated thoracoscopic biopsy confirmed the suspicions. Symptoms have resolved after the steroid pulse therapy and his occupational change. TCE should be taken into consideration as a potential trigger of HP. Early recognition and avoidance of the TCE exposure in the future is important for the treatment of TCE induced HP. PMID:24624216

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

    PubMed

    Caballero, T; Martín-Esteban, M

    1998-01-01

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

  6. Airway Inflammation and Hypersensitivity Induced by Chronic Smoking

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2012-01-01

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

  8. Beta-lactam hypersensitivity and cross-reactivity.

    PubMed

    Terico, Adrienne T; Gallagher, Jason C

    2014-12-01

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

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

    PubMed

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

    2001-08-01

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

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

    PubMed

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

    2010-10-01

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed

    Prescott, William A; Kusmierski, Kristen A

    2007-01-01

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

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

    PubMed Central

    Sabir, Mohammad

    2015-01-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    PubMed

    Limsuwan, Ticha; Demoly, Pascal

    2010-07-01

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

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

    PubMed

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

    2009-01-01

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

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

    PubMed

    Bessmertny, Olga; Pham, Trinh

    2002-01-01

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

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

    PubMed

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

    2014-06-01

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

  19. THE MECHANISM OF ACTION OF CORTISONE IN EXPERIMENTAL HYPERSENSITIVITY

    PubMed Central

    Germuth, Frederick G.

    1953-01-01

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

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

    PubMed

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

    1999-03-01

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

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

    PubMed

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

    2016-11-02

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

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

    PubMed

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

    2010-04-01

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

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

    PubMed

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

    1994-04-01

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

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

    PubMed

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

    2007-01-01

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

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

    PubMed

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

    2008-06-01

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

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

    PubMed

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

    2015-04-07

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

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

    PubMed

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

    2009-09-01

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

  8. Gastroenterology case report of mesalazine-induced cardiopulmonary hypersensitivity

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. [The scientific progress of the "Clinica del Lavoro Luigi Devoto" as seen through the contents of the journal "La Medicina del Lavoro". ].

    PubMed

    Foà, V; Camerino, Donatella

    2003-01-01

    On occasion of the Centenary of the "Clinica del Lavoro Luigi Devoto", its researchers suggested that awareness of its historical identity and scientific development should constitute the basis for the future of the Institution. The directors of the Institute who have succeeded one to the other over the years have left a vivid report of the vast amount of work developed in several research fields and also of the original results achieved with significant impact on the scientific community and on society. Content analysis of "La Medicina del Lavoro" allowed us to shed light on strong bonds existing between manufacturing techniques, work organization and health, in the different political and social periods in which they developed. Many actions have been defined and several research subjects have been renewed (according to current demands and new methodological possibilities) between the past and the present, nevertheless many new approaches need to be taken in the fields of epidemiology, indoor air quality, ergophthalmology, muskuloskeletal disorders, environmental and molecular toxicology, and further research will be undertaken thanks to the potential of this discipline for the future. The aim of this report is also to express our thanks to all the medical and non-medical staff who have made their contribution over 100 years of engagement.

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

    PubMed

    Asselin, Barbara L; Fisher, Vicki

    2014-12-01

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

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

    PubMed

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

    1998-05-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Lucker, Jay R.; Doman, Alex

    2015-01-01

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

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

    PubMed

    Keefer, Laurie; Kahrilas, Peter J

    2016-02-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Noble, Suzanne

    2002-03-01

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

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

    PubMed

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

    2013-12-01

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

  20. Clinical Abacavir Hypersensitivity Reaction among Children in India.

    PubMed

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

    2016-08-01

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

  1. Evaluation of the hypersensitivity potential of alternative butter flavorings

    PubMed Central

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

    2015-01-01

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

  2. Occupational hypersensitivity pneumonitis in a green tea manufacturer.

    PubMed

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

    2016-04-01

    Hypersensitivity pneumonitis (HP) is caused by numerous agents, and one of its histopathological features is poorly formed granulomas. We report here a rare case of occupational HP caused by green tea, showing well-formed granulomas. The patient, a 54-year-old woman who had worked for 15 years in a green tea factory, was referred for abnormal chest X-ray shadows with cough and breathlessness over a 2-month period. The chest X-ray and high-resolution computed tomography showed diffuse bilateral ground-glass opacities and poorly defined centrilobular nodules. Histopathological examination of the thoracoscopic lung biopsy specimens showed bronchiolocentric interstitial pneumonia with well-formed granulomas. Although the form of granulomas were atypical, laboratory data, CT findings, and intradermal skin testing suggested the diagnosis of subacute HP caused by green tea. After transfer to a different department, her condition improved markedly. Taking a precise medical history and avoidance of the suspected environmental agent proved useful in diagnosing this condition. © 2016 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.

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

    PubMed

    Büdinger, L; Hertl, M

    2000-02-01

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

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

    PubMed

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

    2009-04-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

    Aalto-Korte, Kristiina; Mäkinen-Kiljunen, Soili

    2003-07-01

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

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

    PubMed

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

    2013-01-01

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

  8. Diagnosing the tight building syndrome or diagnosing chemical hypersensitivity

    SciTech Connect

    Rogers, S.A. )

    1989-01-01

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

  9. Quantifying serum antibody in bird fanciers' hypersensitivity pneumonitis

    PubMed Central

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

    2006-01-01

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

  10. Hypersensitivity to Aeroallergens in Patients with Nasobronchial Allergy

    PubMed Central

    Balaban, Jagoda; Bijelic, Radojka; Milicevic, Snjezana

    2014-01-01

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

  11. Drug hypersensitivity reactions during hematopoietic stem cell transplantation.

    PubMed

    Bircher, Andreas J; Scherer Hofmeier, Kathrin

    2012-01-01

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

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

    PubMed

    Picard, Matthieu; Castells, Mariana C

    2015-10-01

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

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

    PubMed

    Sykes, L M

    2007-03-01

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

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

    PubMed

    Dickson, Scott D; Salazar, Kimberly C

    2013-08-01

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

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

    PubMed Central

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

    2012-01-01

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

  16. Studies of migration inhibition tests in penicillin hypersensitivity.

    PubMed Central

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

    1979-01-01

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

  17. Concept of experimental preparation for treating dentin hypersensitivity

    PubMed Central

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

    2016-01-01

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

  18. Exploring Some Aspects Associated with Dentine Hypersensitivity in Children

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Ren, Ke; Dubner, Ronald

    2009-01-01

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

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

    PubMed

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

    2006-01-01

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

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

    PubMed

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

    2000-09-01

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

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

    PubMed

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

    2014-01-01

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

  3. FcγRIIa ligation induces platelet hypersensitivity to thrombotic stimuli.

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2017-02-15

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

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

    PubMed Central

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

    1972-01-01

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

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

    PubMed

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

    2013-07-01

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

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

    PubMed

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

    2008-02-01

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

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

    PubMed Central

    McIlwrath, Sabrina L; Westlund, Karin N

    2015-01-01

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

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

    PubMed

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

    2017-02-01

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

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

    PubMed

    Carpenter, David O

    2015-01-01

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

  12. Cellular Tests for the Evaluation of Drug Hypersensitivity.

    PubMed

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

    2016-01-01

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

  13. The role for decorin in delayed-type hypersensitivity

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  16. [The centenary of the founding of the "Clinica del Lavoro Luigi Devoto" in Milan (1902-2002). The oldest health organization in the world for the study, treatment, and prevention of occupational diseases].

    PubMed

    Grieco, A

    2003-01-01

    The foundation of the Clinica del Lavoro by Luigi Devoto cannot be dated back to the specific date of an event or, worse, to the official inauguration as has happened so far. It can rather be considered as a process started on November 20, 1902 (date of the first resolution by the Milan Municipality Council), continuing with the national law n. 365 of July 9, 1905, then with the laying of the first stone on December 11, 1907 bearing the motto of the Milanese School "In aliis vivimus, movemur et sumus" and finally the official inauguration on March 20, 1910. The Founder Luigi Devoto was born in 1864 at Borzonasca (Genoa) and took a degree of medicine and surgery at the Genoa University in 1888. After a period in Prague and then in Genoa, he was appointed temporary teacher of medical pathology in Pavia. He published several scientific contributions in different fields of occupational health (lead intoxication, ankylostomiasis, strain cardiopathy, etc.) and in other branches (tuberculosis, pellagra, etc.) that he considered as indirectly work-related diseases. He died in Milan in 1936. Three issues characterize the ingenious intuition of Luigi Devoto and his thirty-year direction of the Clinica del Lavoro: 1. Full respect for the principles of discipline and scientific method suggested by Bernardino Ramazzini; 2. The extremely broad conception of the diseases that had to be considered as "workers' diseases"; 3. The constant social attention towards the application of scientific knowledge also through workers' information and updating of regulations to improve working conditions. Many of the conflicts and events associated with the foundation of the Clinica del Lavoro can be summarized in the name chosen by the Founder. Actually to those asking why "Clinic of Work" and not "Clinic of Workers", Devoto used to reply that it was work that was ill and therefore it was necessary to treat the work to prevent workers' illnesses.

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

    PubMed

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

    2015-07-01

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

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

    PubMed

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

    2016-02-03

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

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

    PubMed

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

    2011-09-01

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

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

    PubMed Central

    Wang, Bing; Chen, Li-Hua

    2016-01-01

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

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

    PubMed

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

    2010-06-01

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

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

    PubMed Central

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

    1994-01-01

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed

    Torres, Pedro Paulo Teixeira E Silva; Moreira, Marise Amaral Rebouças; Silva, Daniela Graner Schuwartz Tannus; da Gama, Roberta Rodrigues Monteiro; Sugita, Denis Masashi; Moreira, Maria Auxiliadora do Carmo

    2016-01-01

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

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

    PubMed

    Dolan, Sharron; Nolan, Andrea Mary

    2007-08-01

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

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

    PubMed Central

    Al-Khafaji, Hasanain

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2008-10-01

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

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

    PubMed

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

    2007-12-01

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

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

    PubMed

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

    2013-03-01

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

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

    PubMed

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

    2001-01-01

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

  12. Mechanisms of drug hypersensitivity reactions and the skin.

    PubMed

    Kuljanac, Ilko

    2008-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-03-01

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

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

    PubMed

    Scerri, L; Shall, L; Zaki, I

    1993-11-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed

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

    2013-09-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

    Widhani, Alvina; Karjadi, Teguh Harjono

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2002-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2008-02-13

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

  5. Development of ClickClinica: a novel smartphone application to generate real-time global disease surveillance and clinical practice data

    PubMed Central

    2013-01-01

    -producing bodies, clinical governance and public health institutions and also for patient recruitment into ongoing studies. Conclusions Further parallel studies are needed to assess the clinical and epidemiological utility of novel disease surveillance applications, such as this, with direct comparisons made to data collected through routine surveillance routes. Nevertheless, current disease surveillance mechanisms do not always comprehensively and accurately reflect disease distribution for many conditions. Smartphone applications, such as ClickClinica, are a novel approach with the potential to generate real-time disease surveillance data that may augment current methods. PMID:23816161

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

    PubMed

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

    2014-10-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2010-12-01

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

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

    PubMed Central

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

    1994-01-01

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

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

    PubMed

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

    2016-11-01

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

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

    PubMed

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

    2009-08-01

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

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

    PubMed

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

    2011-10-01

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

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

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    1993-05-01

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

  15. "La Clinica Day"

    DTIC Science & Technology

    2002-12-01

    education and occasionally disease screenings for health problems such as high blood pressure or tuberculosis. No clients had experienced health...were identified as having either high blood pressure or high blood sugar readings at the screenings conducted during the health fairs. All of these

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

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2017-04-06

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

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

    PubMed

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

    2009-07-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

    Irritable bowel syndrome (IBS) is a very frequent functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort and alteration of bowel habits. The IBS physiopathology is extremely complex. Visceral hypersensitivity plays an important role in the pathogenesis of abdominal pain in both in vitro and in vivo models of this functional disorder. In order to obtain a general view of the participation of the main ion channels and receptors regarding the visceral hypersensitivity in the IBS and to describe their chemical structure, a literature review was carried out. A bibliographical research in the following electronic databases: Pubmed and Virtual Library in Health (BVS) was fulfilled by using the search terms “ion channels” “or” “receptors” “and” “visceral hypersensitivity” “or” “visceral nociception” “and” “irritable bowel syndrome”. Original and review articles were considered for data acquisition. The activation of the ATP ion-gated channels, voltage-gated sodium (Nav) and calcium (Cav) channels, as well as the activation of protease-activated receptors (PAR2), transient receptor potential vanilloide-1, serotonin, cannabinoids and cholecystokinin are involved in the genesis of visceral hypersensitivity in IBS. The involvement of ion channels and receptors concerning visceral hypersensitivity is noteworthy in IBS models. PMID:24976114

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

    PubMed

    Funke, M; Fellrath, J-M

    2008-08-01

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

  5. Association of CYP1B1 with hypersensitivity induced by taxane therapy in breast cancer patients.

    PubMed

    Rizzo, Roberta; Spaggiari, Federica; Indelli, Monica; Lelli, Giorgio; Baricordi, Olavio R; Rimessi, Paola; Ferlini, Alessandra

    2010-11-01

    Taxanes represent a group of anticancer drugs with a wide range of activity against breast cancer. Therapy side effects include haematologic toxicity (neutropenia, leucopenia), peripheral neuropathy and hypersensitivity, and demonstrate inter-individual variations. Since it is known that three genes are implicated in taxane turnover, namely ABCB1 in the transport, CYP2C8 in the metabolism and CYP1B1 in the activity, we explored the association among polymorphisms (single nucleotide polymorphisms, SNPs) in these three genes and the occurrence of taxane-induced toxicity. We studied 95 patients affected by breast cancer and under treatment with taxanes as adjuvant, metastatic or neo-adjuvant therapy. We genotyped them for SNPs in the CYP2C8 (alleles *1, *2, *3 and *4), CYP1B1 (alleles *1 and *3) and ABCB1 (1236 C>T; 2677 G>T/A; 3435 C>T) genes by real-time PCR assay. We observed a significant association between the CYP1B1*3 allele and a lower occurrence of hypersensitivity reactions to taxane treatment. We speculate that the highest production of 4-hydroxyestradiol (4-OHE2) metabolite by CYP1B1*3 allele could increase the formation of the 4-OHE2-taxane adduct and possibly inhibit taxane toxicity. We suggest that CYP1B1 might affect taxane hypersensitivity therefore representing, if confirmed in a large cohort of patients, an exploratory hypersensitivity predictive biomarker.

  6. USE OF THE RIBONUCLEASE PROTECTION ASSAY FOR IDENTIFYING CHEMICALS WHICH ELLICIT HYPERSENSITIVITY RESPONSES

    EPA Science Inventory

    Use of the Ribonuclease Protection Assay (RPA) for Identifying Chemicals that Elicit Hypersensitivity Responses. L.M. Plitnick, 1, D.M. Sailstad, 2, and R.J. Smialowicz, 2 1UNC, Curriculum in Toxicology, Chapel Hill, NC and 2USEPA, NHEERL, RTP, NC.

    The incidence of aller...

  7. The efficacy of single premedication with antihistamines for radiocontrast media hypersensitivity

    PubMed Central

    Lee, So-Hee; Park, Heung-Woo; Cho, Sang-Heon

    2016-01-01

    Background Single premedication with antihistamines for radiocontrast media (RCM) hypersensitivity is frequently used in real world at the emergent situation although its efficacy is not proven. Objective To evaluate the effect of intravenous antihistamines as a premedication in general population who had experience of mild adverse reactions to iodinated RCM. Methods A retrospective observational study on 14,785 subjects who had RCM-enhanced computed tomography scans between January 2014 and December 2015 in Seoul National University Hospital Gangnam Healthcare Center, Seoul, South Korea. Results Among 453 subjects who had a history of mild RCM-induced hypersensitivity reactions, 273 subjects had a single premedication of intravenous antihistamine. When comparing antihistamine-premedication group and nonpremedication group, there is no protective effect of antihistamines on the incidence rate and severity of hypersensitivity (10.6% vs. 11.7%, p = 0.729). Conclusion The clinical efficacy of a single premedication of antihistamines for mild RCM-induced hypersensitivity was not confirmed. PMID:27489788

  8. Loss of Central Inhibition: Implications for Behavioral Hypersensitivity after Contusive Spinal Cord Injury in Rats

    PubMed Central

    Berrocal, Yerko A.; Almeida, Vania W.; Puentes, Rocio; Knott, Eric P.; Hechtman, Jaclyn F.; Pearse, Damien D.

    2014-01-01

    Behavioral hypersensitivity is common following spinal cord injury (SCI), producing significant discomfort and often developing into chronic pain syndromes. While the mechanisms underlying the development of behavioral hypersensitivity after SCI are poorly understood, previous studies of SCI contusion have shown an increase in amino acids, namely, aspartate and glutamate, along with a decrease in GABA and glycine, particularly below the injury. The current study sought to identify alterations in key enzymes and receptors involved in mediating central inhibition via GABA and glycine after a clinically-relevant contusion SCI model. Following thoracic (T8) 25.0 mm NYU contusion SCI in rodents, significant and persistent behavioral hypersensitivity developed as evidenced by cutaneous allodynia and thermal hyperalgesia. Biochemical analyses confirmed upregulation of glutamate receptor GluR3 with downregulation of the GABA synthesizing enzyme (GAD65/67) and the glycine receptor α3 (GLRA3), notably below the injury. Combined, these changes result in the disinhibition of excitatory impulses and contribute to behavioral hyperexcitability. This study demonstrates a loss of central inhibition and the development of behavioral hypersensitivity in a contusive SCI paradigm. Future use of this model will permit the evaluation of different antinociceptive strategies and help in the elucidation of new targets for the treatment of neuropathic pain. PMID:25180088

  9. Carbamazepine hypersensitivity syndrome triggered by a human herpes virus reactivation in a genetically predisposed patient.

    PubMed

    Calligaris, Lorenzo; Stocco, Gabriele; De Iudicibus, Sara; Marino, Sara; Decorti, Giuliana; Barbi, Egidio; Carrozzi, Marco; Marchetti, Federico; Bartoli, Fiora; Ventura, Alessandro

    2009-01-01

    A case of severe hypersensitivity syndrome, triggered by carbamazepine in the presence of a concomitant active human herpes virus (HHV) 6 and 7 infection is described. To further understand the molecular mechanism of this adverse reaction, analyses of the genetic variants of human leukocyte antigen (HLA) and of the epoxide hydrolase gene (EPHX1), previously associated with carbamazepine hypersensitivity, were performed. A lymphocyte transformation test (LTT) was conducted in order to detect drug-specific lymphocytes. In the hypersensitive patient, 2 genetic factors previously associated with intolerance to carbamazepine were detected: the allele HLA-A*3101 and homozygosity for the variant allele of SNP rs1051740 in EPHX1. Drug-specific lymphocytes could be detected by LTT when the HHV was active (positive PCR for viral DNA and increased anti-HHV 6 IgG titer), but not when it was no longer active. In conclusion, we document a case of severe carbamazepine hypersensitivity triggered by viral reactivation in a patient presenting the interaction of 2 unfavorable genetic factors.

  10. Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions.

    PubMed

    Han, Jiayin; Yi, Yan; Li, Chunying; Zhang, Yushi; Wang, Lianmei; Zhao, Yong; Pan, Chen; Liang, Aihua

    2016-09-13

    The mechanism of penicillin immediate hypersensitivity reactions has not been completely elucidated. These reactions are generally considered to be mediated by IgE, but penicillin-specific IgE could not be detected in most cases. This study demonstrated that penicillin was able to cause vascular hyperpermeability in a mouse model mimicking clinical symptoms of penicillin immediate hypersensitivity reactions. The first exposure to penicillin also induced immediate edema and exudative reactions in ears and lungs of mice in a dose-dependent manner. Vasodilation was noted in microvessels in ears. These reactions were unlikely to be immune-mediated reactions, because no penicillin-specific IgE was produced. Furthermore, penicillin treatment directly elicited rapid histamine release. Penicillin also led to F-actin reorganization in human umbilical vein endothelial cells and increased the permeability of the endothelial monolayer. Activation of the RhoA/ROCK signaling pathway was observed in ears and lungs of mice and in endothelial cells after treatment with penicillin. Both an anti-histamine agent and a ROCK inhibitor attenuated penicillin immediate hypersensitivity reactions in mice. This study presents a novel mechanism of penicillin immediate hypersensitivity reactions and suggests a potential preventive approach against these reactions.

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

    PubMed

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

    2013-12-01

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

  12. DIESEL AND CARBON PARTICLES ENHANCE HOUSE DUST MITE-INDUCED PULMONARY HYPERSENSITIVITY IN BROWN NORWAY RATS

    EPA Science Inventory

    Diesel and Carbon Particles Enhance House Dust Mite-Induced Pulmonary Hypersensitivity in Brown Norway Rats. P. Singh1, M.J. Daniels2, D. Winsett2, J. Richards2, K. Crissman2, M. Madden2 and M.I. Gilmour2. 1NCSU, Raleigh, NC and 2 USEPA, Research Triangle Park, NC.

    Ep...

  13. Reduction in Dental Hypersensitivity with Nano-Hydroxyapatite, Potassium Nitrate, Sodium Monoflurophosphate and Antioxidants#

    PubMed Central

    B. Low, Samuel; Allen, Edward P.; Kontogiorgos, Elias D.

    2015-01-01

    Objective: This clinical study aimed to evaluate effectiveness of a commercially available toothpaste containing potassium nitrate, sodium monoflurophosphate, and nano-hydroxyapatite as well as antioxidants phloretin, ferulic acid and silymarin in reducing dental hypersensitivity in adults. Methods: The clinical trial enrolled patients with a history of dentin hypersensitivity. A test toothpaste was introduced into the daily routine, which included initial instruction on usage. Patients completed a five-question visual analog scale (VAS) at the inception/baseline, after two days and after two weeks of using the toothpaste to determine their level of tooth sensitivity at baseline with the use of the toothpaste over time. Results: Patients that had significant sensitivity at baseline had a range of 52% to 76 % improvement after 48 hours and a range of 70% to 84% improvement after two weeks. Conclusion: A toothpaste containing potassium nitrate, sodium monoflurophosphate, and nano-hydroxyapatite plus antioxidants phloretin, ferulic acid and silymarin applied daily significantly decreased tooth pain of dentin hypersensitivity within a two-day and two-week time period. Clinical Significance: Based on the clinical study results, a daily application of a toothpaste containing potassium nitrate, sodium monofluorophosphate, and nano-hydroxyapatite plus antioxidants phloretin, ferulic acid and silymarin can significantly and quickly reduce tooth pain of dentin hypersensitivity. PMID:25834655

  14. Calcium Efflux as a Component of Hypersensitive Response of Nicotiana benthamiana to Pseudomonas syringae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Using a model plant Nicotiana benthamiana we have demonstrated that initial calcium uptake in response to HR (hypersensitive response)-causing pathogen, P. syringae pv syringae 61 is followed by the net calcium efflux initiated at about 12 hrs after the bacterial challenge and sustained for at least...

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

    PubMed

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

    2009-02-01

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

  16. Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions

    PubMed Central

    Han, Jiayin; Yi, Yan; Li, Chunying; Zhang, Yushi; Wang, Lianmei; Zhao, Yong; Pan, Chen; Liang, Aihua

    2016-01-01

    The mechanism of penicillin immediate hypersensitivity reactions has not been completely elucidated. These reactions are generally considered to be mediated by IgE, but penicillin-specific IgE could not be detected in most cases. This study demonstrated that penicillin was able to cause vascular hyperpermeability in a mouse model mimicking clinical symptoms of penicillin immediate hypersensitivity reactions. The first exposure to penicillin also induced immediate edema and exudative reactions in ears and lungs of mice in a dose-dependent manner. Vasodilation was noted in microvessels in ears. These reactions were unlikely to be immune-mediated reactions, because no penicillin-specific IgE was produced. Furthermore, penicillin treatment directly elicited rapid histamine release. Penicillin also led to F-actin reorganization in human umbilical vein endothelial cells and increased the permeability of the endothelial monolayer. Activation of the RhoA/ROCK signaling pathway was observed in ears and lungs of mice and in endothelial cells after treatment with penicillin. Both an anti-histamine agent and a ROCK inhibitor attenuated penicillin immediate hypersensitivity reactions in mice. This study presents a novel mechanism of penicillin immediate hypersensitivity reactions and suggests a potential preventive approach against these reactions. PMID:27619816

  17. Reducing Auditory Hypersensitivities in Autistic Spectrum Disorder: Preliminary Findings Evaluating the Listening Project Protocol

    PubMed Central

    Porges, Stephen W.; Bazhenova, Olga V.; Bal, Elgiz; Carlson, Nancy; Sorokin, Yevgeniya; Heilman, Keri J.; Cook, Edwin H.; Lewis, Gregory F.

    2014-01-01

    Auditory hypersensitivities are a common feature of autism spectrum disorder (ASD). In the present study, the effectiveness of a novel intervention, the listening project protocol (LPP), was evaluated in two trials conducted with children diagnosed with ASD. LPP was developed to reduce auditory hypersensitivities. LPP is based on a theoretical “neural exercise” model that uses computer altered acoustic stimulation to recruit the neural regulation of middle ear muscles. Features of the intervention stimuli were informed by basic research in speech and hearing sciences that has identified the specific acoustic frequencies necessary to understand speech, which must pass through middle ear structures before being processed by other components of the auditory system. LPP was hypothesized to reduce auditory hypersensitivities by increasing the neural tone to the middle ear muscles to functionally dampen competing sounds in frequencies lower than human speech. The trials demonstrated that LPP, when contrasted to control conditions, selectively reduced auditory hypersensitivities. These findings are consistent with the polyvagal theory, which emphasizes the role of the middle ear muscles in social communication. PMID:25136545

  18. Pharmacogenomics of drug-induced hypersensitivity reactions: challenges, opportunities and clinical implementation.

    PubMed

    Sukasem, Chonlaphat; Puangpetch, Apichaya; Medhasi, Sadeep; Tassaneeyakul, Wichittra

    2014-06-01

    Drug hypersensitivity reactions affect many patients leading to a variety of clinical manifestations, mainly the cutaneous adverse reactions ranging from milder skin reactions to severe cutaneous adverse reactions (SCARs). Hypersensitivity reactions are unpredictable and are thought to have an underlying genetic etiology, as suggested by case reports. With the scientific knowledge of pharmacogenomics and the evidence based on the genomic testing, it is possible to identify genetic predisposing factors for these serious adverse reactions and personalize drug therapy. The most significant genetic associations have been identified in the major histocompatibility complex (MHC) genes encoded for human leukocyte antigens (HLA) alleles. Drugs associated with hypersensitivity reactions with strong genetic predisposing factors include abacavir, nevirapine, carbamazepine, and allopurinol. In this review, strong genetic associations of drug-induced SCARs are highlighted so as to improve drug safety and help to select optimal drugs for individual patients. Further investigation, however, is essential for the characterization of other genes involved in the hypersensitivity reactions with the use of several genetic strategies and technologies.

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

    PubMed

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

    1993-02-01

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

  20. The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats.

    PubMed

    Asgar, J; Zhang, Y; Saloman, J L; Wang, S; Chung, M-K; Ro, J Y

    2015-12-03

    Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is expressed in muscle afferents and direct activation of these receptors induces acute mechanical hypersensitivity. However, the functional role of TRPA1 under pathological muscle pain conditions and mechanisms by which TRPA1 mediate muscle pain and hyperalgesia are not clearly understood. Two rodent behavioral models validated to assess craniofacial muscle pain conditions were used to study ATP- and N-Methyl-D-aspartate (NMDA)-induced acute mechanical hypersensitivity and complete Freund's adjuvant (CFA)-induced persistent mechanical hypersensitivity. The rat grimace scale (RGS) was utilized to assess inflammation-induced spontaneous muscle pain. Behavioral pharmacology experiments were performed to assess the effects of AP18, a selective TRPA1 antagonist under these conditions. TRPA1 expression levels in trigeminal ganglia (TG) were examined before and after CFA treatment in the rat masseter muscle. Pre-treatment of the muscle with AP18 dose-dependently blocked the development of acute mechanical hypersensitivity induced by NMDA and α,β-methylene adenosine triphosphate (αβmeATP), a specific agonist for NMDA and P2X3 receptor, respectively. CFA-induced mechanical hypersensitivity and spontaneous muscle pain responses were significantly reversed by post-treatment of the muscle with AP18 when CFA effects were most prominent. CFA-induced myositis was accompanied by significant up-regulation of TRPA1 expression in TG. Our findings showed that TRPA1 in muscle afferents plays an important role in the development of acute mechanical hypersensitivity and in the maintenance of persistent muscle pain and hypersensitivity. Our data suggested that TRPA1 may serve as a downstream target of pro-nociceptive ion channels, such as P2X3 and NMDA receptors in masseter afferents, and that increased TRPA1 expression under inflammatory conditions may contribute to the maintenance of persistent muscle pain

  1. Molecular Mechanisms for Drug Hypersensitivity Induced by the Malaria Parasite’s Chloroquine Resistance Transporter

    PubMed Central

    Baker, Eileen S.; Webster, Michael W.; Lehane, Adele M.; Shafik, Sarah H.; Martin, Rowena E.

    2016-01-01

    Mutations in the Plasmodium falciparum ‘chloroquine resistance transporter’ (PfCRT) confer resistance to chloroquine (CQ) and related antimalarials by enabling the protein to transport these drugs away from their targets within the parasite’s digestive vacuole (DV). However, CQ resistance-conferring isoforms of PfCRT (PfCRTCQR) also render the parasite hypersensitive to a subset of structurally-diverse pharmacons. Moreover, mutations in PfCRTCQR that suppress the parasite’s hypersensitivity to these molecules simultaneously reinstate its sensitivity to CQ and related drugs. We sought to understand these phenomena by characterizing the functions of PfCRTCQR isoforms that cause the parasite to become hypersensitive to the antimalarial quinine or the antiviral amantadine. We achieved this by measuring the abilities of these proteins to transport CQ, quinine, and amantadine when expressed in Xenopus oocytes and complemented this work with assays that detect the drug transport activity of PfCRT in its native environment within the parasite. Here we describe two mechanistic explanations for PfCRT-induced drug hypersensitivity. First, we show that quinine, which normally accumulates inside the DV and therewithin exerts its antimalarial effect, binds extremely tightly to the substrate-binding site of certain isoforms of PfCRTCQR. By doing so it likely blocks the normal physiological function of the protein, which is essential for the parasite’s survival, and the drug thereby gains an additional killing effect. In the second scenario, we show that although amantadine also sequesters within the DV, the parasite’s hypersensitivity to this drug arises from the PfCRTCQR-mediated transport of amantadine from the DV into the cytosol, where it can better access its antimalarial target. In both cases, the mutations that suppress hypersensitivity also abrogate the ability of PfCRTCQR to transport CQ, thus explaining why rescue from hypersensitivity restores the parasite

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

    PubMed Central

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

    2015-01-01

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

  3. [The study of profile of hypersensitivity to pollen and fungal allergens in the Moscow region].

    PubMed

    Akhapkina, I G; Krakhanenkova, S N; Dobronravova, E V; Shushpanova, E N

    2014-05-01

    The profile of hypersensitivity to pollen and fungal allergens is an important element of common pattern of immune diseases needed for development of effective pharmaceuticals. The purpose of the study was to analyze the rate of detection of combined forms of hypersensitivity to pollen and fungal allergens (pollen of birch, hazel, cocksfoot, wormwood, fungi A. alternata, C. herbarum, R. nigricans, P. notatum, C. albicans, A. fumigatus) in the Moscow region on the basis of data of scarification skin samples. The mono-sensibilization was established in 23.36% of all cases of hypersensitivity. At that, among leading allergens turned out A. alternata and cocksfoot pollen (6.54% and 4.67%), followed by allergens of wormwood pollen, P. notatum, R. nigricans, birch pollen and C. albicans (3.74%, 3.74%, 1.87%, 1.87% and 0.93% correspondingly). The polysensibilization was established in 51.40% of cases. Besides, the combined hypersensitivity to pollen allergens of plants (20.26%) and to pollen and fungal allergens (20.56%) occurred more frequently In the group of patients with polysensibilization predominated combined allergic reactions to pollen allergens and A. alternata allergens (36.36%). On the whole, most frequently occurred sensitization to allergens of birch, hazel, cocksfoot, wormwood and A. alternata allergen (76.14%, 69.32%, 57.95%, 55.68%, 39.77% and 56.82% correspondingly). In the Moscow region predominate combined forms of hypersensitivity to two and more pollen and fungal allergens. The polysensitization to pollen allergens and A. alternata allergen occurs more frequently.

  4. Drug desensitization in the management of hypersensitivity reactions to monoclonal antibodies and chemotherapy.

    PubMed

    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.

  5. Fasting mitigates immediate hypersensitivity: a pivotal role of endogenous D-beta-hydroxybutyrate

    PubMed Central

    2014-01-01

    Background 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. Methods 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 [Ca2+]i responses to compound 48/80 were analyzed in fura 2-loaded rat peritoneal mast cells derived from the ketogenic diet and fasting. Results 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 [Ca2+]i was significantly lower in the ketogenic diet and fasting group than that in the control diet group. Conclusions 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

  6. Low Dose Radiation Hypersensitivity is Caused by p53-dependent Apoptosis

    SciTech Connect

    Enns, L; Bogen, K; Wizniak, J; Murtha, A; Weinfeld, M

    2004-04-08

    Exposure to environmental radiation and the application of new clinical modalities, such as radioimmunotherapy, have heightened the need to understand cellular responses to low dose and low-dose rate ionizing radiation. Many tumor cell lines have been observed to exhibit a hypersensitivity to radiation doses below 50 cGy, which manifests as a significant deviation from the clonogenic survival response predicted by a linear-quadratic fit to higher doses. However, the underlying processes for this phenomenon remain unclear. Using a gel microdrop/flow cytometry assay to monitor single cell proliferation at early times post irradiation, we examined the response of human A549 lung carcinoma, T98G glioma and MCF7 breast carcinoma cell lines exposed to gamma radiation doses from 0 to 200 cGy delivered at 0.18 and 22 cGy/min. The A549 and T98G cells, but not MCF7 cells, showed the marked hypersensitivity at doses <50 cGy. To further characterize the low-dose hypersensitivity, we examined the influence of low-dose radiation on cell cycle status and apoptosis by assays for active caspase-3 and phosphatidylserine translocation (annexin-V binding). We observed that caspase-3 activation and annexin-V binding mirrored the proliferation curves for the cell lines. Furthermore, the low-dose hypersensitivity and annexin-V binding to irradiated A549 and T98G cells were eliminated by treating the cells with pifithrin, an inhibitor of p53. When p53-inactive cell lines (2800T skin fibroblasts and HCT116 colorectal carcinoma cells) were examined for similar patterns, we found that there was no HRS and apoptosis was not detectable by annexin-V or caspase-3 assays. Our data therefore suggest that low-dose hypersensitivity is associated with p53-dependent apoptosis.

  7. Use of cephalosporins in patients with immediate penicillin hypersensitivity: cross-reactivity revisited.

    PubMed

    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.

  8. T-cell-mediated drug hypersensitivity: immune mechanisms and their clinical relevance

    PubMed Central

    Cai, Fenfen; Lee, Frederick J; Pichler, Werner J

    2016-01-01

    T-cell-mediated drug hypersensitivity represents a significant proportion of immune mediated drug hypersensitivity reactions. In the recent years, there has been an increase in understanding the immune mechanisms behind T-cell-mediated drug hypersensitivity. According to hapten mechanism, drug specific T-cell response is stimulated by drug-protein conjugate presented on major histocompatibility complex (MHC) as it is presented as a new antigenic determinant. On the other hand, p-i concept suggests that a drug can stimulate T cells via noncovalent direct interaction with T-cell receptor and/or peptide-MHC. The drug binding site is quite variable and this leads to several different mechanisms within p-i concept. Altered peptide repertoire can be regarded as an 'atypical' subset of p-i concept since the mode of the drug binding and the binding site are essentially identical to p-i concept. However, the intracellular binding of abacavir to HLA-B*57:01 additionally results in alteration in peptide repertoire. Furthermore the T-cell response to altered peptide repertoire model is only shown for abacavir and HLA-B*57:01 and therefore it may not be generalised to other drug hypersensitivity. Danger hypothesis has been postulated to play an important role in drug hypersensitivity by providing signal 2 but its experimental data is lacking at this point in time. Furthermore, the recently described allo-immune response suggests that danger signal may be unnecessary. Finally, in view of these new understanding, the classification and the definition of type B adverse drug reaction should be revised. PMID:27141480

  9. Estrogen-dependent visceral hypersensitivity following stress in rats: An fMRI study.

    PubMed

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

    2016-01-01

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

  10. [The preparation and characterization of fine dusts carried out in the Clinica del Lavoro di Milano in support of experimental studies].

    PubMed

    Occella, E; Maddalon, G; Peruzzo, G F; Foà, V

    1999-01-01

    This paper aims to illustrate the conditions selected at the Clinica del Lavoro of the University of Milan to prepare and analyze a large number of fine dust samples produced over a period of about 50 years, that were initially used for studies within the Clinic performed in its own facilities, and since 1956 were sent to other Italian and overseas laboratories (Luxembourg, UK, Germany, Norway, Sweden, South Korea, USA). The total quantity of material distributed (with maximum size 7-10 microns) was about 2 kg and consisted of the following mineral and artificial compounds: quartz, HF-treated quartz, tridymite, HF-treated tridymite, cristobalite, chromite, anthracite, quartz sand for foundry moulds, sand from the Lybian desert, vitreous silica, pumice, cement, as well small quantities of metallic oxides, organic resins, chrysotile, crocidolite, fibres (vitreous, cotton and polyamidic). About half of the entire quantity of dusts produced consisted of partially HF-treated tridymite. Initially, research on the etiology of silicosis used quartz dust samples, simply sieved or ventilated (consisting of classes finer than 0.04 mm, containing a 15-20% respirable fraction). From 1956 to 1960 the dusts were produced by manual grinding in an agate mortar, below about 10 microns, starting from quartz from Quincinetto (near Ivrea, Province of Turin), containing about 99.5% quartz: particle size and composition were checked using an optical-petrographic technique, with identification of the free and total silica content. Subsequently, the dusts used for biological research were obtained by grinding coarse material with a cast iron pestle and planetary mills, agate and corundum jars. The grinding products were sized by means of centrifugal classification, using the selector developed by N. Zurlo, ensuring control of dust size both optically and by means of wet levigators and hydraulic classifiers (in cooperation with the Institute of Mines of Turin Polytechnic School). After 1990

  11. Involvement of protein kinase ζ in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity

    PubMed Central

    Chen, Aiqin; Bao, Chengjia; Tang, Ying; Luo, Xiaoqing; Guo, Lixia; Liu, Bin

    2015-01-01

    The hippocampal long-term potentiation (LTP) was implicated in the formation of visceral hypersensitivity in rats with irritable bowel syndrome in our previous study. Recent studies have shown that protein kinase M ζ (PKMζ) may be responsible for the maintenance of LTP in memory formation. However, it remains unclear whether PKMζ is involved in the visceral hypersensitivity. In this study, a rat model of visceral hypersensitivity was generated by neonatal maternal separation (NMS). The visceral hypersensitivity was assessed by recording responses of the external oblique abdominal muscle to colorectal distension. Our results demonstrated that hippocampal LTP and visceral hypersensitivity were enhanced significantly in rats of NMS. ζ-Pseudosubstrate inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the expression of hippocampal phosphorylated PKMζ (p-PKMζ) significantly increased in rats of NMS. In addition, bilateral intrahippocampal injections of ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The maximal inhibition was observed at 30 min, and significant inhibition lasted for 1.5–2 h after ZIP application. Besides, data from the open-field test and Morris water maze showed that ZIP did not influence the movement and spatial procedural memory in rats of NMS. In conclusion, p-PKMζ might be a critical protein in the maintenance of hippocampal LTP, which could result in visceral hypersensitivity. PMID:25761958

  12. Involvement of protein kinase ζ in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity.

    PubMed

    Chen, Aiqin; Bao, Chengjia; Tang, Ying; Luo, Xiaoqing; Guo, Lixia; Liu, Bin; Lin, Chun

    2015-05-01

    The hippocampal long-term potentiation (LTP) was implicated in the formation of visceral hypersensitivity in rats with irritable bowel syndrome in our previous study. Recent studies have shown that protein kinase M ζ (PKMζ) may be responsible for the maintenance of LTP in memory formation. However, it remains unclear whether PKMζ is involved in the visceral hypersensitivity. In this study, a rat model of visceral hypersensitivity was generated by neonatal maternal separation (NMS). The visceral hypersensitivity was assessed by recording responses of the external oblique abdominal muscle to colorectal distension. Our results demonstrated that hippocampal LTP and visceral hypersensitivity were enhanced significantly in rats of NMS. ζ-Pseudosubstrate inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the expression of hippocampal phosphorylated PKMζ (p-PKMζ) significantly increased in rats of NMS. In addition, bilateral intrahippocampal injections of ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The maximal inhibition was observed at 30 min, and significant inhibition lasted for 1.5-2 h after ZIP application. Besides, data from the open-field test and Morris water maze showed that ZIP did not influence the movement and spatial procedural memory in rats of NMS. In conclusion, p-PKMζ might be a critical protein in the maintenance of hippocampal LTP, which could result in visceral hypersensitivity.

  13. Histone hyperacetylation modulates spinal type II metabotropic glutamate receptor alleviating stress-induced visceral hypersensitivity in female rats

    PubMed Central

    Cao, Dong-Yuan; Bai, Guang; Ji, Yaping; Karpowicz, Jane

    2016-01-01

    Stress is often a trigger to exacerbate chronic pain including visceral hypersensitivity associated with irritable bowel syndrome, a female predominant functional bowel disorder. Epigenetic mechanisms that mediate stress responses are a potential target to interfere with visceral pain. The purpose of this study was to examine the effect of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, on visceral hypersensitivity induced by a subchronic stressor in female rats and to investigate the involvement of spinal glutamate receptors. Three daily sessions of forced swim induced visceral hypersensitivity. Intrathecal suberoylanilide hydroxamic acid prevented or reversed the stress-induced visceral hypersensitivity, increased spinal histone 3 acetylation and increased mGluR2 and mGluR3 expression. Chromatin immunoprecipitation (ChIP) analysis revealed enrichment of H3K9Ac and H3K18Ac at several promoter Grm2 and Grm3 regions. The mGluR2/3 antagonist LY341495 reversed the inhibitory effect of suberoylanilide hydroxamic acid on the stress-induced visceral hypersensitivity. In surprising contrast, stress and/or suberoylanilide hydroxamic acid had no effect on spinal NMDA receptor expression or function. These data reveal histone modification modulates mGluR2/3 expression in the spinal cord to attenuate stress-induced visceral hypersensitivity. HDAC inhibitors may provide a potential approach to relieve visceral hypersensitivity associated with irritable bowel syndrome. PMID:27385724

  14. Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD database and the GALEN platform. The Galenda project.

    PubMed

    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.

  15. Enhanced in vitro phagocytic power of macrophages from PPD-stimulated skin sites in human subjects hypersensitive to PPD

    PubMed Central

    Magliulo, E.; De Feo, V.; Stirpe, A.; Riva, C.; Scevola, D.

    1973-01-01

    By a quantitative Rebuck's skin-window technique human macrophages were collected from individuals either unreactive or hypersensitive to PPD, the latter having recovered from tuberculous infection. In vitro testing of macrophages with a strain of Paracolonbacter aerogenoides proved that cells from hypersensitive convalescents were provided with increased pagocytic and bactericidal activities. An even higher degree of macrophage activation was attained when cells from hypersensitive individuals had previously been stimulated in vitro with PPD. Changes of macrophage functions such as those mentioned above might well result from the action on macrophages of lympho-kine-like agents released by sensitized lymphocytes coming in contact with PPD. PMID:4579779

  16. Basophil activation test for investigation of IgE-mediated mechanisms in drug hypersensitivity.

    PubMed

    Steiner, Markus; Harrer, Andrea; Lang, Roland; Schneider, Michael; Ferreira, Tima; Hawranek, Thomas; Himly, Martin

    2011-09-16

    Hypersensitivity reactions against non-steroidal anti-inflammatory drugs (NSAIDs) like propyphenazone (PP) and diclofenac (DF) can manifest as Type I-like allergic reactions (1). In clinical practice, diagnosis of drug hypersensitivity is mainly performed by patient history, as skin testing is not reliable and oral provocation testing bears life-threatening risks for the patient (2). Hence, evidence for an underlying IgE-mediated pathomechanism is hard to obtain. Here, we present an in vitro method based on the use of human basophils derived from drug-hypersensitive patients that mimics the allergic effector reaction in vivo. As basophils of drug-allergic patients carry IgE molecules specific for the culprit drug, they become activated upon IgE receptor crosslinking and release allergic effector molecules. The activation of basophils can be monitored by the determination of the upregulation of CD63 surface expression using flow cytometry (3). In the case of low molecular weight drugs, conjugates are designed to enable IgE receptor crosslinking on basophils. As depicted in Figure 1, two representatives of NSAIDs, PP and DF, are covalently bound to human serum albumin (HSA) via a carboxyl group reacting with the primary amino group of lysine residues. DF carries an intrinsic carboxyl group and, thus, can be used directly (4), whereas a carboxyl group-containing derivative of PP had to be organochemically synthesized prior to the study (1). The coupling degree of the low molecular weight compounds on the protein carrier molecule and their spatial distribution is important to guarantee crosslinking of two IgE receptor molecules. The here described protocol applies high performance-size exclusion chromatography (HPSEC) equipped with a sequential refractive index (RI) and ultra violet (UV) detection system for determination of the coupling degree. As the described methodology may be applied for other drugs, the basophil activation test (BAT) bears the potential to be

  17. A rare case of pseudotumor formation associated with methyl methacrylate hypersensitivity in a patient following cemented total knee arthroplasty.

    PubMed

    Kenan, Shachar; Kahn, Leonard; Haramati, Noga; Kenan, Samuel

    2016-08-01

    Hypersensitivity to orthopedic implant materials has been well documented with potential catastrophic consequences if not addressed pre-operatively. The spectrum of reactions is wide, from mild non-specific pain with localized erythema to severe periprosthetic inflammatory destruction and pseudotumor formation. It is therefore essential to identify patients who have or are at risk for implant-associated hypersensitivity. Although metal sensitivity is commonly cited as the cause of these reactions, methyl methacrylate (MMA) has rarely been implicated. To the best of our knowledge, methyl methacrylate-associated pseudotumor formation has not yet been described. The following is a case report of a 68-year-old female who, after undergoing a routine cemented right total knee arthroplasty, developed a painless, enlarging mass during a 13-year period. This mass was found to be a pseudotumor in association with methyl methacrylate hypersensitivity. A review of pseudotumor pathogenesis, methyl methacrylate hypersensitivity, and preoperative preventative care is discussed.

  18. Androgen hypersensitivity in prostate cancer: molecular perspectives on androgen deprivation therapy strategies.

    PubMed

    Foley, Ruth; Marignol, Laure; Keane, John P; Lynch, Thomas H; Hollywood, Donal

    2011-04-01

    Androgen deprivation therapy is initially successful in treating advanced prostate cancer. However, after a period of time tumors inevitably recur. Improved understanding of the various biochemical causes of resistance to hormonal therapy is of crucial importance for developing more effective therapeutic strategies in this cohort of patients. This review discusses the preclinical evidence for androgen hypersensitivity (AH), as a mechanism by which tumors become hormone-refractory (HR). We propose that the growth of some such tumors may be not only stimulated by, but also dependent on low hormone levels, and furthermore, that normal hormone concentrations can have an inhibitory effect on growth. The incidence and importance of AH merits further investigation both in preclinical studies and during clinical trials of intermittent androgen withdrawal or testosterone replacement. We suggest that a subset of HR prostate cancer patients who have androgen-hypersensitive tumors could be particularly amenable to these treatments. Finally, potential approaches for developing biomarkers to identify such patients are explored.

  19. Amalgam contact hypersensitivity lesion: an unusual presentation-report of a rare case.

    PubMed

    Ramnarayan, Bk; Maligi, Pm; Smitha, T; Patil, Us

    2014-09-01

    Amalgam or its components may cause Type IV hypersensitivity reactions on the oral mucosa. These amalgam contact hypersensitivity lesions (ACHL) present as white striae and plaques, erythematous, erosive, atrophic, or ulcerative lesions. Postinflammatory pigmentation in such lesions and pigmentation due to amalgam incorporation in the soft tissue have been reported in the literature. However, ACHL presenting primarily as a black pigmented lesion is extremely rare if not reported. The clinician should be aware of one such presentation of ACHL; we report a unique case of ACHL in a 30-year-old female with such a pigmented lesion in close contact with amalgam restorations. The lesion regressed considerably in a year after replacement of the restoration with posterior composites.

  20. Micronucleus assay in human fibroblasts: a measure of spontaneous chromosomal instability and mutagen hypersensitivity

    SciTech Connect

    Rudd, N.L.; Hoar, D.I.; Greentree, C.L.; Dimnik, L.S.; Hennig, U.S.S.

    1988-01-01

    By comparing fibroblast strains derived from individuals exhibiting chromosome instability and/or mutagen hypersensitivity (Cockayne syndrome, ataxia telangiectasia, and Fanconi anemia) with strains derived from health donors, the fibroblast micronucleus assay has been established as a reproducible measure of the genotypic variation in spontaneous or mitomycin C (MMC)-induced chromosomal instability. The patient strains that were moderately or exquisitely sensitive to MMC could be distinguished readily from the control strains, both in levels of spontaneous micronuclei and in sensitivity to MMC, whereas the mildly sensitive strain (Cockayne syndrome) overlapped with the control range. The reproducibility of the assay was evaluated within and between experiments. In addition to its value as a test system for genotoxins, the fibroblast micronucleus assay may be useful for investigating genetically determined hypersensitivity to mutagens, elevated spontaneous chromosomal breakage, and chromosome segregation errors.

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

    PubMed Central

    Estibeiro, Anita Sandhya Mendonca; Mesquita, Anthony Menezes

    2016-01-01

    Hypersensitivity Pneumonitis (HP) or Extrinsic Allergic Alveolitis (EAA) is a disease resulting from immunologically induced inflammation in response to inhalation of a wide variety of airborne allergens. The condition develops mainly in non atopic individuals sensitized to organic dust due to repeated exposures. It is a relatively rare disease constituting upto 2% of interstitial lung diseases. Knowledge of classical High Resolution Computed Tomography (HRCT) of lung findings aid in early diagnosis. We report a case of subacute hypersensitivity pneumonitis in a housewife who despite being symptomatic remained undiagnosed for two years. She showed a good response to therapy, but soon relapsed. Visit to her home revealed that she lived in a damp house full of moldy walls. PMID:26894116

  2. Further characterisation of allergens associated with hypersensitivity to the "green nimitti" midge (Cladotanytarsus lewisi, Diptera: Chironomidae).

    PubMed

    Tee, R D; Cranston, P S; Kay, A B

    1987-01-01

    Chironomid midges are small (2-15 mm) non-biting flies, characteristically seen swarming by water at dusk. Allergens of the "green nimitti" midge, Cladotanytarsus lewisi (Freeman) (Diptera: Chironomidae), a cause of widespread hypersensitivity in the Sudan, were isolated and partially characterized by Sephacryl S200 chromatography. The allergenicity of the fractions was identified by "rocket" autoradiography, RAST inhibition, skin "prick" tests, and the immunoblot technique. The fractions were further analysed by isoelectric focusing and SDS-PAGE. Two major allergens with pI's ranging from 4.3 to 6.0 were identified and had molecular weights of approximately 17,000 and 32,000 daltons, sizes compatible with their being monomeric and dimeric haemoglobins. Since chironomids occur in nuisance numbers worldwide and their haemoglobins have been shown to produce severe hypersensitivity reactions in man, they should be seen as an important potential cause of environmental and occupational allergy.

  3. Enhancement of hypersensitive transitions of rare-earth ions in the near field of nanoobjects

    NASA Astrophysics Data System (ADS)

    Pukhov, K. K.; Sekatskii, S. K.

    2014-05-01

    The change of intensities of optical transitions of atoms, molecules, and their ions in the near field of nanoobjects is of interest for researchers from both basic and applied points of view. The concept of a near field was used as early as the 1960s to study the mechanisms of hypersensitive transitions of rare-earth (RE) ions. In this work, it is once more emphasized that, precisely for these transitions, changes in characteristics under the action of local properties of the medium are especially strong and, correspondingly, these transitions are especially promising for use. The Judd method for the calculation of the intensities of hypersensitive transitions of RE ions taking into account the inhomogeneous ligand field is extended to RE ions in the near field of nanoobjects. A simple analytical expression for the Judd-Ofelt intensity parameter Ω2 for RE ions in the field of spherical nanoparticles of a subwavelength size is derived.

  4. A C. elegans homolog for the UV-hypersensitivity syndrome disease gene UVSSA

    PubMed Central

    Babu, Vipin; Schumacher, Björn

    2016-01-01

    The transcription-coupled repair pathway (TC-NER) plays a vital role in removing transcription-blocking DNA lesions, particularly UV-induced damage. Clinical symptoms of the two TC-NER-deficiency syndromes, Cockayne syndrome (CS) and UV-hypersensitivity syndrome (UVSS) are dissimilar and the underlying molecular mechanism causing this difference in disease pathology is not yet clearly understood. UV-stimulated scaffold protein A (UVSSA) has been identified recently as a new causal gene for UVSS. Here we describe a functional homolog of the human UVSSA gene in the nematode Caenorhabditis elegans, uvs-1 (UVSSA-like-1). Mutations in uvs-1 render the animals hypersensitive to UV-B irradiation and transcription-blocking lesion-inducing illudin-M, similar to mutations in TC-NER deficient mutants. Moreover, we demonstrate that TC-NER factors including UVS-1 are required for the survival of the adult animals after UV-treatment. PMID:27043179

  5. Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity.

    PubMed

    Clayton, Gina M; Wang, Yang; Crawford, Frances; Novikov, Andrey; Wimberly, Brian T; Kieft, Jeffrey S; Falta, Michael T; Bowerman, Natalie A; Marrack, Philippa; Fontenot, Andrew P; Dai, Shaodong; Kappler, John W

    2014-07-03

    T-cell-mediated hypersensitivity to metal cations is common in humans. How the T cell antigen receptor (TCR) recognizes these cations bound to a major histocompatibility complex (MHC) protein and self-peptide is unknown. Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a debilitating inflammatory lung condition caused by the reaction of CD4 T cells to inhaled beryllium. Here, we show that the T cell ligand is created when a Be(2+) cation becomes buried in an HLA-DP2/peptide complex, where it is coordinated by both MHC and peptide acidic amino acids. Surprisingly, the TCR does not interact with the Be(2+) itself, but rather with surface changes induced by the firmly bound Be(2+) and an accompanying Na(+) cation. Thus, CBD, by creating a new antigen by indirectly modifying the structure of preexisting self MHC-peptide complex, lies on the border between allergic hypersensitivity and autoimmunity.

  6. Amalgam Contact Hypersensitivity Lesion: An Unusual Presentation-Report Of A Rare Case

    PubMed Central

    Ramnarayan, BK; Maligi, PM; Smitha, T; Patil, US

    2014-01-01

    Amalgam or its components may cause Type IV hypersensitivity reactions on the oral mucosa. These amalgam contact hypersensitivity lesions (ACHL) present as white striae and plaques, erythematous, erosive, atrophic, or ulcerative lesions. Postinflammatory pigmentation in such lesions and pigmentation due to amalgam incorporation in the soft tissue have been reported in the literature. However, ACHL presenting primarily as a black pigmented lesion is extremely rare if not reported. The clinician should be aware of one such presentation of ACHL; we report a unique case of ACHL in a 30-year-old female with such a pigmented lesion in close contact with amalgam restorations. The lesion regressed considerably in a year after replacement of the restoration with posterior composites. PMID:25364611

  7. [Hypersensitivity to mosquito bite manifested as Skeeter síndrome].

    PubMed

    Pérez-Vanzzini, Rafael; González-Díaz, Sandra Nora; Arias-Cruz, Alfredo; Palma-Gómez, Samuel; Yong-Rodríguez, Adrián; Gutiérrez-Mujica, José Julio; García-Calderín, Diego; Ibarra, Jesús Arturo

    2015-01-01

    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.

  8. A delayed hypersensitivity reaction to a stainless steel crown: a case report.

    PubMed

    Yilmaz, A; Ozdemir, C E; Yilmaz, Y

    2012-01-01

    Stainless steel crowns are commonly used to restore primary or permanent teeth in pediatric restorative dentistry. Here, we describe a case of a delayed hypersensitivity reaction, which manifested itself as perioral skin eruptions, after restoring the decayed first permanent molar tooth of a 13-year-old Caucasian girl with a preformed stainless steel crown. The eruptions completely healed within one week after removal of the stainless steel crown. The decayed tooth was then restored with a bis-acryl crown and bridge. Since no perioral skin eruptions occurred during the six-month follow-up, we presume that the cause of the perioral skin eruptions was a delayed hypersensitivity reaction, which was triggered by the nickel in the stainless steel crown.

  9. Allotype specific interactions of drugs and HLA molecules in hypersensitivity reactions.

    PubMed

    Illing, Patricia T; Mifsud, Nicole A; Purcell, Anthony W

    2016-10-01

    It is hypothesised that associations between adverse drug reactions and specific alleles of the human leukocyte antigens arise due to specific interactions between the human leukocyte antigen molecules and the causative drug that stimulate immune responses targeting drug exposed tissues. To date this has only been definitively demonstrated for abacavir, an antiretroviral that causes a systemic adverse drug reaction, abacavir hypersensitivity syndrome, solely in HLA-B*57:01(+) individuals. Whilst this has informed the modification of abacavir to remove immunogenicity, there remains an imperative to define other interactions between drugs and specific HLA in order to understand the scope of interactions that can drive T cell mediated drug hypersensitivity. Here we review the current state of understanding of these interactions.

  10. Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation.

    PubMed

    van der Sluis, Inge M; Vrooman, Lynda M; Pieters, Rob; Baruchel, Andre; Escherich, Gabriele; Goulden, Nicholas; Mondelaers, Veerle; Sanchez de Toledo, Jose; Rizzari, Carmelo; Silverman, Lewis B; Whitlock, James A

    2016-03-01

    L-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 is the development of neutralizing antibodies and associated asparaginase inactivity. Also problematic in the use of asparaginase is the potential for the development of silent inactivation, with the formation of neutralizing antibodies and reduced asparaginase activity in the absence of a clinically evident allergic reaction. Here we present guidelines for the identification and management of clinical hypersensitivity and silent inactivation with Escherichia coli- and Erwinia chrysanthemi- derived asparaginase preparations. These guidelines were developed by a consensus panel of experts following a review of the available published data. We provide a consensus of expert opinions on the role of serum asparaginase level assessment, indications for switching asparaginase preparation, and monitoring after change in asparaginase preparation.

  11. Safe administration of iron sucrose in a patient with a previous hypersensitivity reaction to ferric gluconate.

    PubMed

    Sane, Radhika; Baribeault, David; Rosenberg, Carol L

    2007-04-01

    A 67-year-old woman with iron deficiency anemia required parenteral iron therapy and was treated with intravenous ferric gluconate. She tolerated the first dose, but after the second dose, she developed a tingling feeling all over her body, along with swelling in her hands and feet, and a rash with hives over most of her body. It was thought that she had likely experienced a hypersensitivity reaction to ferric gluconate. The decision was made to continue therapy; however, two modifications were made. The patient was given dexamethasone, diphenhydramine, and ibuprofen 1 hour before administering the third dose, and the infusion time was prolonged by 1 hour. Approximately 45 minutes after the infusion was completed, the patient developed hives on her arms and legs. At the patient's next clinic visit, it was decided that continuation of parenteral iron repletion was necessary, and the decision was made to attempt a challenge with iron sucrose. The patient was given dexamethasone 8 mg to be taken the night before and the morning of treatment. She successfully completed the iron repletion therapy with iron sucrose. Three parenteral iron products are available in the United States: iron dextran, sodium ferric gluconate complex, and iron sucrose. Iron dextran, the oldest of these products, carries the highest risk for hypersensitivity reactions. Available data suggest that either iron sucrose or ferric gluconate can be safely administered to patients with known hypersensitivity to iron dextran. Our patient's experience implies that it may be possible to safely administer iron sucrose to a patient with hypersensitivity to ferric gluconate. This finding has clinical implications and warrants confirmation in a larger population.

  12. A Hyperresponsive HPA Axis May Confer Resilience Against Persistent Paclitaxel-Induced Mechanical Hypersensitivity

    PubMed Central

    Kozachik, Sharon L.; Page, Gayle G.

    2016-01-01

    Paclitaxel (PAC) treatment is associated with persistent, debilitating neuropathic pain that affects the hands and feet. Female sex and biological stress responsivity are risk factors for persistent pain, but it is unclear whether these important biologically based factors confer risk for PAC-induced neuropathic pain. To determine the relative contributions of sex and hypothalamic–pituitary–adrenal (HPA)-axis stress responsivity to PAC-induced mechanical hypersensitivity, we employed a PAC protocol consisting of three, 2-week cycles of every-other-day doses of PAC 1 mg/kg versus saline (Week 1) and recovery (Week 2), totaling 42 days, in mature male and female Fischer 344, Lewis, and Sprague Dawley (SD) rats, known to differ in HPA axis stress responsivity. Mechanical sensitivity was operationalized using von Frey filaments, per the up–down method. Among PAC-injected rats, SD rats exhibited significantly greater mechanical hypersensitivity relative to accumulative PAC doses compared to Fischer 344 rats. Lewis rats were not significantly different in mechanical hypersensitivity from SD or Fischer 344 rats. At the end of the protocol, PAC-injected SD rats exhibited profound mechanical hypersensitivity, whereas the PAC-injected Fischer 344 rats appeared relatively resilient to the long-term effects of PAC and exhibited mechanical sensitivity that was not statistically different from their saline-injected counterparts. Sex differences were mixed and noted only early in the PAC protocol. Moderate HPA axis stress responsivity may confer additional risk for the painful effects of PAC. If these findings hold in humans, clinicians may be better able to identify persons who may be at increased risks for developing neuropathic pain during PAC therapy. PMID:26512050

  13. Pharmacological activation of 5-HT7 receptors reduces nerve injury-induced mechanical and thermal hypersensitivity.

    PubMed

    Brenchat, Alex; Nadal, Xavier; Romero, Luz; Ovalle, Sergio; Muro, Asunción; Sánchez-Arroyos, Ricard; Portillo-Salido, Enrique; Pujol, Marta; Montero, Ana; Codony, Xavier; Burgueño, Javier; Zamanillo, Daniel; Hamon, Michel; Maldonado, Rafael; Vela, José Miguel

    2010-06-01

    The involvement of the 5-HT(7) receptor in nociception and pain, particularly chronic pain (i.e., neuropathic pain), has been poorly investigated. In the present study, we examined whether the 5-HT(7) receptor participates in some modulatory control of nerve injury-evoked mechanical hypersensitivity and thermal (heat) hyperalgesia in mice. Activation of 5-HT(7) receptors by systemic administration of the selective 5-HT(7) receptor agonist AS-19 (1 and 10mg/kg) exerted a clear-cut reduction of mechanical and thermal hypersensitivities that were reversed by co-administering the selective 5-HT(7) receptor antagonist SB-258719. Interestingly, blocking of 5-HT(7) receptors with SB-258719 (2.5 and 10mg/kg) enhanced mechanical (but not thermal) hypersensitivity in nerve-injured mice and induced mechanical hypersensitivity in sham-operated mice. Effectiveness of the treatment with a 5-HT(7) receptor agonist was maintained after repeated systemic administration: no tolerance to the antiallodynic and antihyperalgesic effects was developed following treatment with the selective 5-HT(7) receptor agonist E-57431 (10mg/kg) twice daily for 11 days. The 5-HT(7) receptor co-localized with GABAergic cells in the dorsal horn of the spinal cord, suggesting that the activation of spinal inhibitory GABAergic interneurons could contribute to the analgesic effects of 5-HT(7) receptor agonists. In addition, a significant increase of 5-HT(7) receptors was found by immunohistochemistry in the ipsilateral dorsal horn of the spinal cord after nerve injury, suggesting a "pain"-triggered regulation of receptor expression. These results support the idea that the 5-HT(7) receptor subtype is involved in the control of pain and point to a new potential use of 5-HT(7) receptor agonists for the treatment of neuropathic pain.

  14. 5-HT7 receptor activation inhibits mechanical hypersensitivity secondary to capsaicin sensitization in mice.

    PubMed

    Brenchat, Alex; Romero, Luz; García, Mónica; Pujol, Marta; Burgueño, Javier; Torrens, Antoni; Hamon, Michel; Baeyens, José Manuel; Buschmann, Helmut; Zamanillo, Daniel; Vela, José Miguel

    2009-02-01

    This work aimed to evaluate the potential role of the 5-HT(7) receptor in nociception secondary to a sensitizing stimulus in mice. For this purpose, the effects of relevant ligands (5-HT(7) receptor agonists: AS-19, MSD-5a, E-55888; 5-HT(7) receptor antagonists: SB-258719, SB-269970; 5-HT(1A) receptor agonist: F-13640; 5-HT(1A) receptor antagonist: WAY-100635) were assessed on capsaicin-induced mechanical hypersensitivity, a pain behavior involving hypersensitivity of dorsal horn neurons (central sensitization). For the 5-HT(7) receptor agonists used, binding profile and intrinsic efficacy to stimulate cAMP formation in HEK-293F cells expressing the human 5-HT(7) receptor were also evaluated. AS-19 and E-55888 were selective for 5-HT(7) receptors. E-55888 was a full agonist whereas AS-19 and MSD-5a behaved as partial agonists, with maximal effects corresponding to 77% and 61%, respectively, of the cAMP response evoked by the full agonist 5-HT. Our in vivo results revealed that systemic administration of 5-HT(7) receptor agonists exerted a clear-cut dose-dependent antinociceptive effect that was prevented by 5-HT(7) receptor antagonists, but not by the 5-HT(1A) receptor antagonist. The order of efficacy (E-55888>AS-19>MSD-5a) matched their in vitro efficacy as 5-HT(7) receptor agonists. Contrary to agonists, a dose-dependent promotion of mechanical hypersensitivity was observed after administration of 5-HT(7) receptor antagonists, substantiating the involvement of the 5-HT(7) receptor in the control of capsaicin-induced mechanical hypersensitivity. These findings suggest that serotonin exerts an inhibitory role in the control of nociception through activation of 5-HT(7) receptors, and point to a new potential therapeutic use of 5-HT(7) receptor agonists in the field of analgesia.

  15. Histamine in the locus coeruleus promotes descending noradrenergic inhibition of neuropathic hypersensitivity.

    PubMed

    Wei, Hong; Jin, Cong-Yu; Viisanen, Hanna; You, Hao-Jun; Pertovaara, Antti

    2014-12-01

    Among brain structures receiving efferent projections from the histaminergic tuberomammillary nucleus is the pontine locus coeruleus (LC) involved in descending noradrenergic control of pain. Here we studied whether histamine in the LC is involved in descending regulation of neuropathic hypersensitivity. Peripheral neuropathy was induced by unilateral spinal nerve ligation in the rat with a chronic intracerebral and intrathecal catheter for drug administrations. Mechanical hypersensitivity in the injured limb was assessed by monofilaments. Heat nociception was assessed by determining radiant heat-induced paw flick. Histamine in the LC produced a dose-related (1-10μg) mechanical antihypersensitivity effect (maximum effect at 15min and duration of effect 30min), without influence on heat nociception. Pretreatment of LC with zolantidine (histamine H2 receptor antagonist), but not with pyrilamine (histamine H1 receptor antagonist), and spinal administration of atipamezole (an α2-adrenoceptor antagonist), prazosine (an α1-adrenoceptor antagonist) or bicuculline (a GABAA receptor antagonist) attenuated the antihypersensitivity effect of histamine. The histamine-induced antihypersensitivity effect was also reduced by pretreatment of LC with fadolmidine, an α2-adrenoceptor agonist inducing autoinhibition of noradrenergic cell bodies. Zolantidine or pyrilamine alone in the LC failed to influence pain behavior, while A-960656 (histamine H3 receptor antagonist) suppressed hypersensitivity. A plausible explanation for these findings is that histamine, due to excitatory action mediated by the histamine H2 receptor on noradrenergic cell bodies, promotes descending spinal α1/2-adrenoceptor-mediated inhibition of neuropathic hypersensitivity. Blocking the autoinhibitory histamine H3 receptor on histaminergic nerve terminals in the LC facilitates release of histamine and thereby, increases descending noradrenergic pain inhibition.

  16. Pilot study of the use of Yin Qiao San in children with conventional antipyretic hypersensitivity

    PubMed Central

    Liew, Woei Kang; Chiang, Wen Chin; Goh, Anne; Chay, Oh Moh; Iancovici Kidon, Mona

    2015-01-01

    Background Children with a diagnosis of cross-reactive hypersensitivity to both paracetamol and nonsteroidal anti-inflammatory drugs are limited in their choice of antipyretics. Objective The aim of this pilot study is to evaluate the feasibility of using a Chinese proprietary medicine, Yin Qiao San (YQS), for fever relief. Methods A single centre, open label, prospective clinical trial exploring the tolerability and feasibility of using YQS for fever relief in children who are unable to use conventional antipyretic medications. Children between 1-18 years of age with hypersensitivity to multiple antipyretics were recruited. Eligible participants underwent an oral provocation test with YQS. Children who passed the oral provocation test were instructed to take a prescribed dose of YQS when the temperature was >38.0℃ and continued till the fever settled. Time taken for fever resolution and any adverse events were collected. Results A total of 21 children, mean age 10.7 years, had a diagnosis of paracetamol and ibuprofen hypersensitivity. All except one patient successfully tolerated an oral challenge of YQS. Of the 88 doses of YQS taken for fever over 38.0℃, 16 (18%) had documented temperature reduction 2 hours after ingestion and 30 (34%) had documented temperature reduction 4 hours after ingestion. There were 2 reports of urticaria after YQS use which were attributed to flare of recurrent spontaneous urticaria during the illness. None of the patients developed symptoms of circulatory compromise or respiratory distress. Conclusion YQS is generally well tolerated in patients with paracetamol and ibuprofen hypersensitivity. PMID:26539405

  17. Hypersensitivity to aeroallergens in adult patients with atopic dermatitis develops due to the different immunological mechanisms.

    PubMed

    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.

  18. High cytokinin levels induce a hypersensitive-like response in tobacco

    PubMed Central

    Novák, Jan; Pavlů, Jaroslav; Novák, Ondřej; Nožková-Hlaváčková, Vladimíra; Špundová, Martina; Hlavinka, Jan; Koukalová, Šárka; Skalák, Jan; Černý, Martin; Brzobohatý, Břetislav

    2013-01-01

    Background and Aims Cytokinins are positive regulators of shoot development. However, it has previously been demonstrated that efficient activation of the cytokinin biosynthesis gene ipt can cause necrotic lesions and wilting in tobacco leaves. Some plant pathogens reportedly use their ability to produce cytokinins in disease development. In response to pathogen attacks, plants can trigger a hypersensitive response that rapidly kills cells near the infection site, depriving the pathogen of nutrients and preventing its spread. In this study, a diverse set of processes that link ipt activation to necrotic lesion formation were investigated in order to evaluate the potential of cytokinins as signals and/or mediators in plant defence against pathogens. Methods The binary pOp-ipt/LhGR system for dexamethasone-inducible ipt expression was used to increase endogenous cytokinin levels in transgenic tobacco. Changes in the levels of cytokinins and the stress hormones salicylic, jasmonic and abscisic acid following ipt activation were determined by ultra-performance liquid chromatography–electrospray tandem mass spectrometry (UPLC-MS/MS). Trends in hydrogen peroxide content and lipid peroxidation were monitored using the potassium iodide and malondialdehyde assays. The subcellular distribution of hydrogen peroxide was investigated using 3,3′-diaminobenzidine staining. The dynamics of transcripts related to photosynthesis and pathogen response were analysed by reverse transcription followed by quantitative PCR. The effects of cytokinins on photosynthesis were deciphered by analysing changes in chlorophyll fluorescence and leaf gas exchange. Key Results Plants can produce sufficiently high levels of cytokinins to trigger fast cell death without any intervening chlorosis – a hallmark of the hypersensitive response. The results suggest that chloroplastic hydrogen peroxide orchestrates the molecular responses underpinning the hypersensitive-like response, including the

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

    PubMed

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

    2016-04-15

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

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

    PubMed Central

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

    2016-01-01

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

  1. Drug Hypersensitivity: How Drugs Stimulate T Cells via Pharmacological Interaction with Immune Receptors.

    PubMed

    Pichler, Werner J; Adam, Jacqueline; Watkins, Stephen; Wuillemin, Natascha; Yun, James; Yerly, Daniel

    2015-01-01

    Small chemicals like drugs tend to bind to proteins via noncovalent bonds, e.g. hydrogen bonds, salt bridges or electrostatic interactions. Some chemicals interact with other molecules than the actual target ligand, representing so-called 'off-target' activities of drugs. Such interactions are a main cause of adverse side effects to drugs and are normally classified as predictable type A reactions. Detailed analysis of drug-induced immune reactions revealed that off-target activities also affect immune receptors, such as highly polymorphic human leukocyte antigens (HLA) or T cell receptors (TCR). Such drug interactions with immune receptors may lead to T cell stimulation, resulting in clinical symptoms of delayed-type hypersensitivity. They are assigned the 'pharmacological interaction with immune receptors' (p-i) concept. Analysis of p-i has revealed that drugs bind preferentially or exclusively to distinct HLA molecules (p-i HLA) or to distinct TCR (p-i TCR). P-i reactions differ from 'conventional' off-target drug reactions as the outcome is not due to the effect on the drug-modified cells themselves, but is the consequence of reactive T cells. Hence, the complex and diverse clinical manifestations of delayed-type hypersensitivity are caused by the functional heterogeneity of T cells. In the abacavir model of p-i HLA, the drug binding to HLA may result in alteration of the presenting peptides. More importantly, the drug binding to HLA generates a drug-modified HLA, which stimulates T cells directly, like an allo-HLA. In the sulfamethoxazole model of p-i TCR, responsive T cells likely require costimulation for full T cell activation. These findings may explain the similarity of delayed-type hypersensitivity reactions to graft-versus-host disease, and how systemic viral infections increase the risk of delayed-type hypersensitivity reactions.

  2. Zeta Inhibitory Peptide as a Novel Therapy to Control Chronic Visceral Hypersensitivity in a Rat Model

    PubMed Central

    Chen, Yu; Guo, Lixia; Dai, Hengfen; Huang, Yang; Chen, Qianqian; Lin, Chun

    2016-01-01

    Background The pathogenesis of multiple chronic visceral pain syndromes, such as irritable bowel syndrome (IBS), is not well known, and as a result current therapies are ineffective. The objective of this study was to investigate the effect of spinal protein kinase M zeta (PKMζ) on visceral pain sensitivity in rats with IBS to better understand the pathogenesis and investigate the effect of zeta inhibitory peptide (ZIP) as a therapy for chronic visceral pain. Methods Visceral hypersensitivity rats were produced by neonatal maternal separation (NMS). Visceral pain sensitivity was assessed by electromyographic (EMG) responses of abdominal muscles to colorectal distention (CRD). Spinal PKMζ and phosphorylated PKMζ (p-PKMζ) were detected by western blot. Varying doses of ZIP were intrathecally administered to investigate the role of spinal PKMζ in chronic visceral hypersensitivity. The open field test was used to determine if ZIP therapy causes spontaneous motor activity side effects. Results Graded CRD pressure significantly increased EMG responses in NMS rats compared to control rats (p < 0.05). p-PKMζ expression increased in the thoracolumbar and lumbosacral spinal cord in the IBS-like rats with notable concomitant chronic visceral pain compared to control rats (p < 0.05). EMG data revealed that intrathecal ZIP injection (1, 5, and 10 μg) dose-dependently attenuated visceral pain hypersensitivity in IBS-like rats. Conclusions Phosphorylated PKMζ may be involved in the spinal central sensitization of chronic visceral hypersensitivity in IBS, and administration of ZIP could effectively treat chronic visceral pain with good outcomes in rat models. PMID:27776136

  3. In vitro diagnosis of immediate IgE-mediated drug hypersensitivity: warnings and (unmet) needs.

    PubMed

    Uyttebroek, Astrid P; Sabato, Vito; Bridts, Chris H; Ebo, Didier G

    2014-08-01

    Immediate drug hypersensitivity reactions (DHR) constitute an important health condition, with serious consequences of inadequate diagnosis. In this article, some of the most important issues related to in vitro diagnosis of IgE-mediated allergies are discussed. In vitro diagnostics will benefit from expanded and novel insights and understandings in drug chemical reactivity, protein binding, biotransformation, degradation, identification of (cross-reactive) drug antigenic determinants, and deeper understanding of sensitization routes. Collective efforts should be undertaken to activate fundamental and clinical investigations.

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

    NASA Astrophysics Data System (ADS)

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

    2001-10-01

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

  5. Management of patients with nonaspirin-exacerbated respiratory disease aspirin hypersensitivity reactions.

    PubMed

    Saff, Rebecca R; Banerji, Aleena

    2015-01-01

    Because of widespread use, nonsteroidal anti-inflammatory drugs (NSAIDs) are the second most common cause of all adverse drug reactions, with hypersensitivity reported in ∼1% of the population. NSAID hypersensitivity can be categorized into five types by the underlying disease, symptoms of reaction, and timing of reaction. These include rhinitis and asthma induced by NSAIDs (also known as aspirin-exacerbated respiratory disease), NSAID-exacerbated cutaneous disease (NECD), urticaria or angioedema induced by multiple NSAIDs, single NSAID-induced reactions, and delayed NSAID reactions. NECD occurs in one-third of patients with chronic urticaria who develop an exacerbation of their urticaria, sometimes with angioedema, typically beginning 30-90 minutes after ingestion of NSAIDs that inhibit cyclooxygenase (COX)-1. In urticaria or angioedema induced by multiple NSAIDs, patients without underlying disease develop urticaria or angioedema 30-90 minutes after ingestion of COX-1-inhibiting NSAIDs including aspirin. Single NSAID-induced reactions are immediate and specific to a single NSAID and are thought to occur because of an IgE-mediated reaction against a specific epitope of the NSAID. Delayed NSAID reactions occur days to weeks after initiating an NSAID. These are T-cell mediated and not amenable to desensitization or rechallenge. Classifying the type of NSAID hypersensitivity is important because many patients with a prior history of urticaria or angioedema induced by multiple NSAIDs will often tolerate aspirin test dose. This would allow the use of an aspirin for primary or secondary prevention in patients with coronary artery disease despite a presumed history of NSAID hypersensitivity.

  6. Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons.

    PubMed

    Langeslag, Michiel; Constantin, Cristina E; Andratsch, Manfred; Quarta, Serena; Mair, Norbert; Kress, Michaela

    2011-12-23

    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.

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

    PubMed Central

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

    2004-01-01

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

  8. Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde.

    PubMed

    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.

  9. Duodenal administered seal oil for patients with subjective food hypersensitivity: an explorative open pilot study

    PubMed Central

    Gregersen, Kine; Lind, Ragna A; Valeur, Jørgen; Bjørkkjær, Tormod; Berstad, Arnold; Lied, Gülen Arslan

    2010-01-01

    Short-term duodenal administration of n-3 polyunsaturated fatty acid (PUFA)-rich seal oil may improve gastrointestinal complaints in patients with subjective food hypersensitivity, as well as joint pain in patients with inflammatory bowel disease (IBD). The aim of the present explorative pilot study was to investigate whether 10-day open treatment with seal oil, 10 mL self-administrated via a nasoduodenal tube 3 times daily, could also benefit nongastrointestinal complaints and quality of life (QoL) in patients with subjective food hypersensitivity. Twenty-six patients with subjective food hypersensitivity, of whom 25 had irritable bowel syndrome (IBS), were included in the present study. Before and after treatment and 1 month posttreatment, patients filled in the Ulcer Esophagitis Subjective Symptoms Scale (UESS) and the Gastrointestinal Symptom Rating Scale (GSRS) for gastrointestinal symptoms and subjective health complaints (SHC) inventory for nongastrointestinal symptoms in addition to short form of the Nepean dyspepsia index (SF-NDI) for evaluation of QoL. Compared with baseline, gastrointestinal, as well as nongastrointestinal, complaints and QoL improved significantly, both at end of treatment and 1 month posttreatment. The consistent improvements following seal oil administration warrant further placebo-controlled trials for confirmation of effect. PMID:21189836

  10. Eight International London Cough Symposium 2014: Cough hypersensitivity syndrome as the basis for chronic cough.

    PubMed

    Chung, Kian Fan; Canning, Brendan; McGarvey, Lorcan

    2015-12-01

    At the Eighth International London Cough Conference held in London in July 2014, the focus was on the relatively novel concept of cough hypersensitivity syndrome (CHS) as forming the basis of chronic cough. This concept has been formulated following understanding of the neuronal pathways for cough and a realisation that not all chronic cough is usually associated with a cause. The CHS is defined by troublesome coughing triggered by low level of thermal, mechanical or chemical exposure. It also encompasses other symptoms or sensations such as laryngeal hypersensitivity, nasal hypersensitivity and possibly also symptoms related to gastrooesopahgeal reflux. The pathophysiologic basis of the CHS is now being increasingly linked to an enhancement of the afferent pathways of the cough reflex both at the peripheral and central levels. Mechanisms involved include the interactions of inflammatory mechanisms with cough sensors in the upper airways and with neuronal pathways of cough, associated with a central component. Tools for assessing CHS in the clinic need to be developed. New drugs may be developed to control CHS. A roadmap is suggested from the inception of the CHS concept towards the development of newer antitussives at the Symposium.

  11. A novel regulatory mechanism of naringenin through inhibition of T lymphocyte function in contact hypersensitivity suppression

    SciTech Connect

    Fang, Feng; Tang, Yijun; Gao, Zhe; Xu, Qiang

    2010-06-25

    Naringenin, a flavonoid in grapefruits and citrus fruits, has been reported to exhibit anti-inflammatory and anti-oxidative activities. Contact hypersensitivity (CHS) is a T cell-mediated immune reaction, and the factors released from macrophages also contribute to this response. Previous studies showed that naringenin suppressed CHS by inhibiting activation and migration of macrophages. However, little is known about naringenin's effects on T lymphocytes. Our study indicated that naringenin potently suppressed picryl chloride (PCl)-induced contact hypersensitivity by inhibiting the proliferation and activation of T lymphocytes. In vitro, both of the activated hapten-specific T cells and the T cells stimulated with anti-CD3/anti-CD28 showed growth arrest after naringenin treatment. Furthermore, naringenin reduced CD69 (the protein level) and cytokines such as IL-2, TNF-{alpha}, and IFN-{gamma} (the mRNA level) expressions which highly expressed by activated T cells. Meanwhile, naringenin also induced T cell apoptosis by upregulation of Bax, Bad, PARP, cleaved-caspase 3 and downregulation of phosphorylated Akt, Bcl-2. These findings suggest that, besides its anti-inflammatory activities in macrophages, naringenin also showed inhibitory effects on the activation and proliferation of T cells to alleviate symptoms of contact hypersensitivity.

  12. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back.

    PubMed

    Schrijvers, Rik; Gilissen, Liesbeth; Chiriac, Anca Mirela; Demoly, Pascal

    2015-01-01

    Drug hypersensitivity reactions (DHR) have been present since the advent of drugs. In particular T-cell mediated delayed-type hypersensitivity reactions represent a heterogeneous clinical entity with a diverse pathogenesis and result in a considerable burden of morbidity and mortality not only driven by the reactions themselves but also by the use of alternatives which are sometimes less effective or even more dangerous. Diagnostic procedures rely on clinical history, skin testing and potential provocation testing, whereas validated in vitro diagnostic procedures are still lacking for most of them. Recent work in the field of pharmacogenomics combined with basic scientific research has provided insights in the pathogenesis of abacavir and carbamazepine hypersensitivities linked with certain human leucocyte antigen risk alleles. Nevertheless, important scientific questions on how other DHR arise and how host-drug interactions occur, remain unanswered. Recent work indicates an intricate relation between host, drug and pathogens in severe cutaneous and systemic reactions and provides more insights in the role of regulatory T-cells and viral reactivation in these reactions. In this review we focus on type IV delayed-type DHR, and address recent advances in the pathogenesis, pharmacogenomics, and diagnosis of these reactions with an emphasis on the understandings arising from basic research.

  13. New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity.

    PubMed

    Pirmohamed, Munir; Ostrov, David A; Park, B Kevin

    2015-08-01

    Drug hypersensitivity reactions are an important clinical problem for both health care and industry. Recent advances in genetics have identified a number of HLA alleles associated with a range of these adverse reactions predominantly affecting the skin but also other organs, such as the liver. The associations between abacavir hypersensitivity and HLA-B*57:01 and carbamazepine-induced Stevens-Johnson syndrome and HLA-B*15:02 have been implemented in clinical practice. There are many different mechanisms proposed in the pathogenesis of drug hypersensitivity reactions, including the hapten hypothesis, direct binding to T-cell receptors (the pharmacologic interaction hypothesis), and peptide-binding displacement. A problem with all the hypotheses is that they are largely based on in vitro findings, with little direct in vivo evidence. Although most studies have focused on individual mechanisms, it is perhaps more important to consider them all as being complementary, potentially occurring at the same time with the same drug in the same patient. This might at least partly account for the heterogeneity of the immune response seen in different patients. There is a need to develop novel methodologies to evaluate how the in vitro mechanisms relate to the in vivo situation and how the highly consistent genetic findings with different HLA alleles can be more consistently used for both prediction and prevention of these serious adverse reactions.

  14. The hypersensitive glucocorticoid response specifically regulates period 1 and expression of circadian genes.

    PubMed

    Reddy, Timothy E; Gertz, Jason; Crawford, Gregory E; Garabedian, Michael J; Myers, Richard M

    2012-09-01

    Glucocorticoids regulate gene expression by binding and activating the glucocorticoid receptor (GR). While ligand affinity determines the global sensitivity of the response, additional proteins act on the genome to tune sensitivity of some genes. However, the genomic extent and specificity of dose-specific glucocorticoid responses are unknown. We show that dose-specific glucocorticoid responses are extraordinarily specific at the genomic scale, able to distinctly express a single gene, the circadian rhythm gene for Period 1 (PER1), at concentrations consistent with the nighttime nadir of human cortisol. We mapped the PER1 response to a single GR binding site. The specific GR binding sequence did not impact sensitivity, and we instead attributed the response to a combination of additional transcription factors and chromatin accessibility acting in the same locus. The PER1 hypersensitive response element is conserved in the mouse, where we found similar upregulation of Per1 in pituitary cells. Targeted and transient overexpression of PER1 led to regulation of additional circadian rhythm genes hours later, suggesting that hypersensitive expression of PER1 impacts circadian gene expression. These findings show that hypersensitive GR binding occurs throughout the genome, drives targeted gene expression, and may be important to endocrine mediation of peripheral circadian rhythms.

  15. Influence of PUVA and UVB radiation on delayed hypersensitivity in the guinea pig

    SciTech Connect

    Morison, W.L.; Parrish, J.A.; Woehler, M.E.; Krugler, J.I.; Bloch, K.J.

    1981-06-01

    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.

  16. Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.

    PubMed

    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.

  17. Is Tadpole Pupil in an Adolescent Girl Caused by Denervation Hypersensitivity?

    PubMed

    Hansen, Jonas Kjeldbjerg; Møller, Hans Ulrik

    2017-01-04

    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.

  18. Metal hypersensitivity in total knee arthroplasty: revision surgery using a ceramic femoral component - a case report.

    PubMed

    Bergschmidt, Philipp; Bader, Rainer; Mittelmeier, Wolfram

    2012-03-01

    We present a case involving the revision of a total knee arthroplasty with a metal femoral component using a ceramic implant due to metal hypersensitivity. A 58-year-old female patient underwent total knee arthroplasty (TKA) with a standard metal bicondylar knee system. She suffered from persistent pain and strong limitations in her range of motion (ROM) associated with flexion during the early postoperative period. Arthroscopic arthrolysis of the knee joint and intensive active and passive physical treatment, in combination with a cortisone regime, temporarily increased the ROM and reduced pain. No signs of low grade infection or other causes of implant failure were evident. Histology of synovial tissue revealed lymphoplasmacellular fibrinous tissue, consistent with a type IV allergic reaction. Allergometry (skin reaction) revealed type IV hypersensitivity against nickel-II-sulfate and palladium chloride. Revision surgery of the metal components was performed with a cemented ceramic femoral component (same bicondylar design) and a cemented titanium alloy tibial component. Postoperative evaluations were performed 10days, and 3 and 12months after the revision surgery. There was an increased ROM in flexion to 90° at the 12month follow-up. No swelling or effusion was observed at all clinical examinations after the revision surgery. No pain at rest and moderate walking pain were evident. The presented case demonstrates that ceramic implants are a promising solution for patients suffering from hypersensitivity to metal ions in total knee arthroplasty.

  19. A World Allergy Organization International Survey on Diagnostic Procedures and Therapies in Drug Allergy/Hypersensitivity

    PubMed Central

    Mirakian, Rita; Castells, Mariana; Pichler, Werner; Romano, Antonino; Bonadonna, Patrizia; Diana, Deleanu; Kowalski, Marek; Yanez, Anahi; Lleonart, Ramon; Sanchez-Borges, Mario; Demoly, Pascal

    2011-01-01

    Objective To study the diagnostic and treatment modalities used in drug allergy/hypersensitivity among members of the World Allergy Organization (WAO). Methods A questionnaire comprising 39 questions was circulated electronically to member societies, associate member societies, and regional and affiliate organizations of WAO between June 29, 2009, and August 9, 2009. Results Eighty-two responses were received. Skin testing was used by 74.7%, with only 71.4% having access to penicillin skin test reagents. In vitro–specific IgE tests were used by 67.4%, and basophil activation test was used by 54.4%. Lymphocyte transformation tests were used by 36.8% and patch tests by 54.7%. Drug provocation tests were used by 68.4%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (76.9%). Rapid desensitization for chemotherapy, antibiotics, or biologic agents was used by 69.6%. Systemic corticosteroid was used in the treatment of Stevens–Johnson syndrome by 72.3%, and high-dose intravenous immunoglobulins in toxic epidermal necrolysis by 50.8%. Human leukocyte antigen screening before prescription of abacavir was used by 92.9% and before prescription of carbamazepine by 21.4%. Conclusions Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across WAO member societies. PMID:23268453

  20. Anaesthesia-associated hypersensitivity reactions: seven years' data from a British bi-specialty clinic.

    PubMed

    Low, A E; McEwan, J C; Karanam, S; North, J; Kong, K-L

    2016-01-01

    Our bi-specialty clinic was established to systematically investigate patients with suspected peri-operative hypersensitivity reactions. Four hundred and ten patients were studied; 316 following an intra-operative reaction ('postoperative' group) and 94 with a previous history of reaction, referred before undergoing anaesthesia ('pre-operative' group). In the postoperative group, 173 (54.7%) were diagnosed with IgE-mediated reactions: 65 (37.6%) to neuromuscular blocking drugs; 54 (31.2%) antibiotics; 15 (8.7%) chlorhexidine and 12 (6.9%) patent blue dye. Reactions were severe in 114 patients (65.9%). All reactions to patent blue dye were severe. We identified IgE sensitisation in 22 (13.2%) cases with isolated mucocutaneous reactions. Only 173 (54.7%) patients had serum tryptase samples taken. Referrers' suspected causal agent was confirmed in only 37.2% of patients. Of 94 patients reviewed 'pre-operatively', 29 (30.8%) were diagnosed with IgE-mediated hypersensitivity reactions, reinforcing the importance of investigating this group of patients. Knowledge of the range of causative agents identified in our study should guide the investigation of suspected peri-operative hypersensitivity reactions.

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

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

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

  2. Arithmetic facts storage deficit: the hypersensitivity-to-interference in memory hypothesis.

    PubMed

    De Visscher, Alice; Noël, Marie-Pascale

    2014-05-01

    Dyscalculia, or mathematics learning disorders, is currently known to be heterogeneous (Wilson & Dehaene, ). While various profiles of dyscalculia coexist, a general and persistent hallmark of this math learning disability is the difficulty in memorizing arithmetic facts (Geary, Hoard & Hamson, ; Jordan & Montani, ; Slade & Russel, ). Arithmetic facts are simple arithmetic problems that are solved by direct retrieval from memory. Recently, De Visscher and Noël () showed hypersensitivity-to-interference in memory in an adult suffering from a specific deficit of arithmetic facts storage. According to the authors, arithmetic facts share many features. The overlapping of these features between arithmetic facts may provoke interference. Consequently, learners who are hypersensitive-to-interference could have considerable difficulties in storing arithmetic facts. The present study aims at testing this new hypothesis on fourth-grade children who are learning multiplication tables. Among 101 children that were assessed, 23 low arithmetic facts learners were selected because of their low score in arithmetic facts fluency (controlling for processing speed). Twenty-three control children were selected, matched for classroom, gender, and age. In addition to a subtest of global reasoning, these participants were given a multiplication production task and a memorization task of low- and high-interference associations. The results show that children with low arithmetic fluencies experience hypersensitivity-to-interference in memory compared with children with typical arithmetic fluencies.

  3. Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases

    PubMed Central

    Ceuleers, Hannah; Van Spaendonk, Hanne; Hanning, Nikita; Heirbaut, Jelena; Lambeir, Anne-Marie; Joossens, Jurgen; Augustyns, Koen; De Man, Joris G; De Meester, Ingrid; De Winter, Benedicte Y

    2016-01-01

    Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling molecules through the activation of protease-activated receptors (PARs). Based on their chemical mechanism for catalysis, proteases can be classified into several classes: serine, cysteine, aspartic, metallo- and threonine proteases represent the mammalian protease families. In particular, the class of serine proteases will play a significant role in this review. In the last decades, proteases have been suggested to play a key role in the pathogenesis of visceral hypersensitivity, which is a major factor contributing to abdominal pain in patients with inflammatory bowel diseases and/or irritable bowel syndrome. So far, only a few preclinical animal studies have investigated the effect of protease inhibitors specifically on visceral sensitivity while their effect on inflammation is described in more detail. In our accompanying review we describe their effect on gastrointestinal permeability. On account of their promising results in the field of visceral hypersensitivity, further research is warranted. The aim of this review is to give an overview on the concept of visceral hypersensitivity as well as on the physiological and pathophysiological functions of proteases herein. PMID:28058009

  4. Ocular delayed hypersensitivity: a pathogenetic mechanism of chlamydial-conjunctivitis in guinea pigs.

    PubMed Central

    Watkins, N G; Hadlow, W J; Moos, A B; Caldwell, H D

    1986-01-01

    We used a naturally occurring, Chlamydia psittaci-caused eye disease in guinea pigs, guinea pig inclusion conjunctivitis, as an animal model to understand both the immune response and the pathogenesis of chlamydial eye infections. When instilled into the conjunctival sac of guinea pigs that had been previously infected and were immune, viable chlamydiae or a Triton X-100-soluble extract of them produced a short-lived (12-48 hr) eye disease indistinguishable clinically and histologically from that observed during primary chlamydial eye infection. The clinical and histologic findings were consistent with those of ocular delayed hypersensitivity. Ocular delayed hypersensitivity was induced by primary chlamydial infection at mucosal sites other than conjunctival, such as vaginal and intestinal. Preliminary characterization of the hypersensitivity allergen shows that it is heat sensitive and common to the genus Chlamydia. The allergen is apparently not surface-exposed on chlamydiae and requires viable but not replicating organisms for activity. Our observation should be useful in understanding pathogenetic mechanisms of Chlamydia trachomatis-caused infections in humans, in particular those that produce chronic inflammatory diseases, such as blinding trachoma and urogenital diseases. Images PMID:3463978

  5. Edrophonium provocative testing for the evaluation of upper gastrointestinal hypersensitivity in patients with nonulcer dyspepsia.

    PubMed

    Tsutsui, Shinichi; Mine, Kazunori; Handa, Masanori; Hayashi, Haruo; Hosoi, Masako; Kinukawa, Naoko; Kubo, Chiharu

    2006-08-01

    The aim of this study was to examine if edrophonium provocative testing is useful for evaluating upper gastrointestinal hypersensitivity in patients with nonulcer dyspepsia (NUD). A questionnaire rating dyspeptic symptoms was done for 58 patients with NUD. The patients were then given an intravenous infusion of saline followed by 5 mg of edrophonium. Baseline esophageal manometry was also done. Patients whose usual symptoms were reproduced (48.3%) had significantly higher symptom scores (13.0 [8.5, 17.0] vs. 8.5 [6.0, 11.0]; P = 0.015) and a significantly higher number of symptoms (4.0 [2.5, 6.0] vs. 3.0 [1.0, 4.0]; P = 0.010) than patients whose usual symptoms were not reproduced. The presence of an esophageal motility disorder was not significantly different between the two groups. These findings suggest upper gastrointestinal hypersensitivity in the patients whose symptoms were reproduced. Edrophonium provocative testing might be useful for evaluating upper gastrointestinal hypersensitivity in patients with NUD.

  6. Anisakis simplex: from obscure infectious worm to inducer of immune hypersensitivity.

    PubMed

    Audicana, M Teresa; Kennedy, Malcolm W

    2008-04-01

    Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites ("gastroallergic anisakiasis"), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive.

  7. Effects and mechanisms of auricular electroacupuncture on gastric hypersensitivity in a rodent model of functional dyspepsia

    PubMed Central

    Zhou, Jingzhu; Li, Shiying; Wang, Yinping; Lei, Yong; Foreman, Robert D.; Yin, Jieyun; Chen, Jiande D. Z.

    2017-01-01

    Background Functional dyspepsia (FD) is a common functional gastrointestinal disease, and abdominal pain is one of the main symptoms. The aim of this study was to explore the effects and mechanisms of auricular electro-acupuncture (AEA) on gastric hypersensitivity in a rodent model of FD. Methods Ten-day-old pups were gavaged with 0.2 ml of 0.1% iodoacetamide daily for 6 days. AEA at the “stomach” point with different parameters or sham-EA was performed on 8-week-old animals. Gastric sensitivity to gastric distention was measured under different conditions. Autonomic functions were assessed from the spectral analysis of heart rate variability (HRV) derived from the electrocardiogram. Naloxone was injected intraperitoneally before AEA to explore the opioid mechanism. Gastric emptying was measured at the end of the study. Results 1) Gastric sensitivity to gastric distention was higher in the FD rats. AEA with parameters of 0.1s on, 0.4s off, 100Hz, 0.3ms and 0.4–0.5mA, but not other parameters or sham-EA, decreased gastric hypersensitivity in the FD rats. Naloxone did not block the effect of AEA. 2) Lower vagal activity and higher sympathovagal ratio were noted in the FD rats, compared with the controls. AEA increased vagal activity and improved sympathovagal imbalance. Conclusions AEA ameliorates gastric hypersensitivity in FD rats and this effect may be attributed to the improvement of sympathovagal balance. PMID:28350818

  8. Morphological and morphometric studies of the airways of sheep with acute airway hypersensitivity to inhaled Ascaris suum.

    PubMed

    Chen, W; Alley, M R; Manktelow, B W

    1991-10-01

    The airways of 12 sheep with naturally-occurring allergic airway hypersensitivity, six of which had changes in both airway resistance and dynamic lung compliance (Group A) and six of which had changes in only dynamic lung compliance (Group B), were compared quantitatively with six non-reacting sheep (Group C) in order to examine the relation between airway hypersensitivity and various morphological features thought to be related to airway hypersensitivity. Compared to the non-reacting sheep (Group C), the hypersensitive sheep (Groups A and B) had a thinner epithelium in medium bronchi and bronchioles, fewer goblet cells in bronchioles, and greater gland area at most airway levels. The differences of the gland dimensions and the types of mucosubstance between hypersensitive and non-reacting animals were more variable. No significant differences between the three groups were noted with regard to luminal occlusion or epithelial sloughing and squamous metaplasia. Although there was a positive association between epithelial thickness and goblet cell density in the small airways, the development of allergic airway hypersensitivity in sheep may occur in the absence of major morphological changes in the airway epithelium.

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

    PubMed

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

    2009-02-01

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

  10. Hypersensitivity of bronchial asthmatics to cockroach in Taiwan. comparative study between American and German cockroaches.

    PubMed

    Tsai, J J; Kao, M H; Wu, C H

    1998-11-01

    This study was performed to test the hypersensitivity of asthmatics to American and German cockroaches, which are both common in Taiwan. A total of 236 asthmatic patients received skin prick test using allergen extracts from both American and German cockroaches, and 596 sera from asthmatic patients were analyzed for their specific IgE against German cockroach extract. The results of skin test showed that 39.4 and 36.4% asthmatic patients were hypersensitive to American and German cockroaches. Fifteen among 236 patients were only allergic to American cockroaches and 8 were only allergic to German cockroaches. Using the Pharmacia CAP system, 36% of the sera were found to contain the specific IgE to German cockroach extract. Eighty-nine sera positive for German cockroach extract were then tested for their reactivity to American cockroach extract using the fluoroallergosorbent test (FAST). Sixty among 89 (68%) of their sera contained American cockroach-specific IgE. The correlation coefficient between both parameters was r = 0.45. Immunoblot and immunoblot inhibition studies were performed to analyze the IgE-binding components and the cross-reactivity between American and German cockroaches. The results showed that there are different IgE-binding components between American and German cockroaches. Sera containing specific IgE to both species of cockroach were absorbed with both species of cockroach extracts. The specific IgE to German cockroaches can be absorbed by American cockroach extract in all selected sera and the specific IgE to American cockroaches can only partially be absorbed by German cockroaches. The nonabsorbed allergens in American cockroaches had molecular weights of 33 and 50 kD. In conclusion, one-third of the asthmatic population tested was allergic to cockroaches. Although most cockroach-hypersensitive patients were allergic to both American and German cockroaches, more asthmatic patients were allergic to American cockroaches in Taiwan. The use of

  11. The Validity of Claims-Based Algorithms to Identify Serious Hypersensitivity Reactions and Osteonecrosis of the Jaw.

    PubMed

    Wright, Nicole C; Curtis, Jeffrey R; Arora, Tarun; Smith, Wilson K; Kilgore, Meredith L; Saag, Kenneth G; Safford, Monika M; Delzell, Elizabeth S

    2015-01-01

    Validation of claims-based algorithms to identify serious hypersensitivity reactions and osteonecrosis of the jaw has not been performed in large osteoporosis populations. The objective of this project is to estimate the positive predictive value of the claims-based algorithms in older women with osteoporosis enrolled in Medicare. Using the 2006-2008 Medicare 5% sample data, we identified potential hypersensitivity and osteonecrosis of the jaw cases based on ICD-9 diagnosis codes. Potential hypersensitivity cases had a 995.0, 995.2, or 995.3 diagnosis code on emergency department or inpatient claims. Potential osteonecrosis of the jaw cases had ≥1 inpatient or outpatient physician claim with a 522.7, 526.4, 526.5, or 733.45 diagnosis code or ≥2 claims of any type with a 526.9 diagnosis code. All retrieved records were redacted and reviewed by experts to determine case status: confirmed, not confirmed, or insufficient information. We calculated the positive predictive value as the number of confirmed cases divided by the total number of retrieved records with sufficient information. We requested 412 potential hypersensitivity and 304 potential osteonecrosis of the jaw records and received 174 (42%) and 84 (28%) records respectively. Of 84 potential osteonecrosis of the jaw cases, 6 were confirmed, resulting in a positive predictive value (95% CI) of 7.1% (2.7, 14.9). Of 174 retrieved potential hypersensitivity records, 95 were confirmed. After exclusion of 25 records with insufficient information for case determination, the overall positive predictive value (95% CI) for hypersensitivity reactions was 76.0% (67.5, 83.2). In a random sample of Medicare data, a claim-based algorithm to identify serious hypersensitivity reactions performed well. An algorithm for osteonecrosis of the jaw did not, partly due to the inclusion of diagnosis codes that are not specific for osteoporosis of the jaw.

  12. Dissociation between the relief of skeletal pain behaviors and skin hypersensitivity in a model of bone cancer pain.

    PubMed

    Guedon, Jean-Marc G; Longo, Geraldine; Majuta, Lisa A; Thomspon, Michelle L; Fealk, Michelle N; Mantyh, Patrick W

    2016-06-01

    Recent studies have suggested that in humans and animals with significant skeletal pain, changes in the mechanical hypersensitivity of the skin can be detected. However, whether measuring changes in skin hypersensitivity can be a reliable surrogate for measuring skeletal pain itself remains unclear. To explore this question, we generated skeletal pain by injecting and confining GFP-transfected NCTC 2472 osteosarcoma cells unilaterally to the femur of C3H male mice. Beginning at day 7 post-tumor injection, animals were administered vehicle, an antibody to the P2X3 receptor (anti-P2X3) or anti-NGF antibody. Pain and analgesic efficacy were then measured on days 21, 28, and 35 post-tumor injection using a battery of skeletal pain-related behaviors and von Frey assessment of mechanical hypersensitivity on the plantar surface of the hind paw. Animals with bone cancer pain treated with anti-P2X3 showed a reduction in skin hypersensitivity but no attenuation of skeletal pain behaviors, whereas animals with bone cancer pain treated with anti-NGF showed a reduction in both skin hypersensitivity and skeletal pain behaviors. These results suggest that although bone cancer can induce significant skeletal pain-related behaviors and hypersensitivity of the skin, relief of hypersensitivity of the skin is not always accompanied by attenuation of skeletal pain. Understanding the relationship between skeletal and skin pain may provide insight into how pain is processed and integrated and help define the preclinical measures of skeletal pain that are predictive end points for clinical trials.

  13. [Characteristics of hypersensitivity syndrome to lamotrigine: review of one case reported in the Regional Center of Pharmacovigilance of Nantes].

    PubMed

    Veyrac, G; Marcade, G; Chiffoleau, A; Bourin, M; Jolliet, P

    2002-01-01

    Drug-induced hypersensitivity syndrome is an uncommon but potentially life-threatening idiosyncratic drug reaction. In the literature, about five cases have been reported concerning hypersensitivity syndrome with lamotrigine. Most cases concern aromatic anticonvulsants but we report a case induced by lamotrigine which is a non aromatic anticonvulsant. A 73-year-old man was treated with lamotrigine for epilepsy due to a cerebrovascular stroke for 5 weeks. After 2 weeks with a single oral dose of 50 mg lamotrigine, the patient received 100 mg. Quickly thereafter fever, erythema and edema involving the periorbital area appeared. He was then admitted to hospital and lamotrigine was immediately discontinued. He developed acute hepatic and renal failure. During his hospital stay, he was treated with systemic and topical corticosteroids. After slow improvement, he was discharged 4 weeks later. Concerning this typical case, we review the characteristics of hypersensitivity syndrome and the different etiopathogenesis. The hypersensitivity syndrome typically develops two to six weeks after a drug is first administered, later than most other serious skin reactions. This syndrome manifests as rash, fever, tender lymphadenopathy, hepatitis and eosinophilia. The mechanism of hypersensitivity syndrome is unknown. Several theories have been proposed. The reaction is secondary to circulating antibodies or concerns toxic metabolities. On the other hand, association of human herpes virus 6 infection may play a role in the development of hypersensitivity syndrome. Hypersensitivity reactions to the aromatic antiepileptic drugs appear to have an immune etiology much like lamotrigine: bioactivation, detoxification, covalent adduct formation, processing and presentation of antigen to the immune system, and consequent formation of antibody and T-cell immune effectors. Another theory involves toxic metabolites; the aromatic antiepileptic agents are metabolised by cytochrome P-450 to an

  14. [Hypersensitivity to pollen of Olea europea in patients with pollen allergy in the area of Zadar and Dubrovnik].

    PubMed

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

    2004-01-01

    Olive pollen is one of the most important causes of inhalant allergy in countries around the Mediterranean sea. Due to the lack of information on hypersensitivity to the pollen of Olea europea from Croatian coast, the aim of this investigation was to establish the frequency of hypersensitivity to the pollen of Olea europea in pollen allergic patients in Zadar and Dubrovnik. Also, we compared two areas of Dalmatia regarding the number of patients and expression of allergy to the Olea europea. A total of 810 patients, children and adults, with pollen allergy were examined in both areas, Zadar and Dubrovnik. In the area of Zadar we examined 546 participants and in the area of Dubrovnik 264 participants. The patients were assessed by anamnestic data, clinical examination, measurement of pulmonary function (adults and children older than 7 years), skin prick test and enzymo-immunologic UniCAP test for measurements of specific IgE antibodies. For statistical analysis we used chi square test. Hypersensitivity to the allergy of Olea europea occurred in 66/810 (8.15%) assessed participants with pollen allergy. The comparison between the two areas didn't show any statistical difference in the number of affected participants with hypersensitivity to the Olea europea. Also, we didn't show any statistical difference in comparison of skin prick tests, immunologic measurements of specific IgE antibodies, or clinical manifestations between participants in the two investigated areas. The most prevalent clinical manifestation was rhinitis registered in 39/66 (59%) patients with hypersensitivity to the olive pollen. The majority of patients with hypersensitivity to olive pollen 51/66 (77%) live in towns. Only 3/66 (4%) participants live on an island. Rhinitis was the most prevalent clinical manifestation in our patients with hypersensitivity to allergen of Olea europea. Hypersensitivity to olive pollen was higher in participants who lived in towns. The hypersensitivity to Olea

  15. Use of lymphoblastoid cell lines to evaluate the hypersensitivity to ultraviolet radiation in Cockayne syndrome

    SciTech Connect

    Otsuka, F.; Tarone, R.E.; Cayeux, S.; Robbins, J.H.

    1984-05-01

    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.

  16. Schisandra chinensis reverses visceral hypersensitivity in a neonatal-maternal separated rat model.

    PubMed

    Yang, Jia-Ming; Xian, Yan-Fang; Ip, Paul S P; Wu, Justin C Y; Lao, Lixing; Fong, Harry H S; Sung, Joseph J Y; Berman, Brian; Yeung, John H K; Che, Chun-Tao

    2012-03-15

    Visceral hypersensitivity is an important characteristic feature of functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). This study evaluated the effect of Schisandra chinensis on visceral hyperalgesia induced by neonatal maternal separation (NMS) in an IBS rat model. The visceromotor responses to colorectal balloon distension (CRD) were measured by abdominal withdrawal reflex (AWR) and electromyographic (EMG) activities. NMS control rats (receiving vehicle) underwent aggravated visceral pain in response to CRD as compared to normal rats, evidenced by the reduced pain threshold, enhanced AWR scores and EMG responses. Treatment with a 70% ethanol extract of S. chinensis (0.3g/kg and 1.5g/kg/day) for 7 days resulted in an increase in the pain threshold (NMS control: 19.1±1.0mmHg vs low-dose: 24.8±1.3mmHg and high-dose: 25.2±1.8mmHg, p<0.01), and abolished the elevated AWR and EMG responses to CRD in NMS rats (AUC values of EMG response curve were: 1952±202 in NMS control group vs 1074±90 in low-dose group and 1145±92 in high-dose group, p<0.001), indicating that S. chinensis could reverse the visceral hypersensitivity induced by early-life stress event. The result of ELSA measurement shows that the elevated serotonin (5-HT) level in the distal colon of NMS rats returned to normal level after treatment with S. chinensis. Moreover, the increase in pain threshold in rats treated with S. chinensis was associated with a decline of the mRNA level of 5-HT(3) receptor in the distal colon. All available results demonstrate that S. chinensis can reverse visceral hypersensitivity induced by neonatal-maternal separation, and the effect may be mediated through colonic 5-HT pathway in the rat.

  17. Schisandra chinensis reverses visceral hypersensitivity in a neonatal-maternal separated rat model

    PubMed Central

    Yang, Jia-Ming; Xian, Yan-Fang; Ip, Paul SP; Wu, Justin CY; Lao, Lixing; Fong, Harry HS; Sung, Joseph JY; Berman, Brian; Yeung, John HK; Che, Chun-Tao

    2012-01-01

    Visceral hypersensitivity is an important characteristic feature of functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). This study evaluated the effect of Schisandra chinensis on visceral hyperalgesia induced by neonatal maternal separation (NMS) in an IBS rat model. The visceromotor responses to colorectal balloon distension (CRD) were measured by abdominal withdrawal reflex (AWR) and electromyographic activities (EMG). NMS control rats (receiving vehicle) underwent aggravated visceral pain in response to CRD as compared to normal rats, evidenced by the reduced pain threshold, enhanced AWR scores and EMG responses. Treatment with a 70% ethanol extract of S. chinensis (0.3 g/kg and 1.5 g/kg per day) for seven days resulted in an increase in the pain threshold (NMS control: 19.1 ± 1.0 mmHg vs low-dose: 24.8 ± 1.3 mmHg and high-dose: 25.2 ± 1.8 mmHg, p<0.01), and abolished the elevated AWR and EMG responses to CRD in NMS rats (AUC values of EMG response curve were: 1952 ± 202 in NMS control group vs 1074 ± 90 in low-dose group and 1145 ± 92 in high-dose group, p<0.001), indicating that S. chinensis could reverse the visceral hypersensitivity induced by early-life stress event. The result of ELSA measurement shows that the elevated serotonin (5-HT) level in the distal colon of NMS rats returned to normal level after treatment with S. chinensis. Moreover, the increase in pain threshold in rats treated with S. chinensis was associated with a decline of the mRNA level of 5-HT3 receptor in the distal colon. All available results demonstrate that S. chinensis can reverse visceral hypersensitivity induced by neonatal-maternal separation, and the effect may be mediated through colonic 5-HT pathway in the rat. PMID:22230486

  18. Noninflammatory upregulation of nerve growth factor underlies gastric hypersensitivity induced by neonatal colon inflammation

    PubMed Central

    Li, Qingjie; Winston, John H.

    2015-01-01

    Gastric hypersensitivity is one of the key contributors to the postprandial symptoms of epigastric pain/discomfort, satiety, and fullness in functional dyspepsia patients. Epidemiological studies found that adverse early-life experiences are risk factors for the development of gastric hypersensitivity. Preclinical studies found that neonatal colon inflammation elevates plasma norepinephrine (NE), which upregulates expression of nerve growth factor (NGF) in the muscularis externa of the gastric fundus. Our goal was to investigate the cellular mechanisms by which NE upregulates the expression of NGF in gastric hypersensitive (GHS) rats, which were subjected previously to neonatal colon inflammation. Neonatal colon inflammation upregulated NGF protein, but not mRNA, in the gastric fundus of GHS rats. Western blotting showed upregulation of p110γ of phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K), phosphoinositide-dependent kinase-1 (PDK1), pAKT(Ser473), and phosphorylated 4E-binding protein (p4E-BP1)(Thr70), suggesting AKT activation and enhanced NGF protein translation. AKT inhibitor MK-2206 blocked the upregulation of NGF in the fundus of GHS rats. Matrix metalloproteinase 9 (MMP-9), the major NGF-degrading protease, was suppressed, indicating that NGF degradation was impeded. Incubation of fundus muscularis externa with NE upregulated NGF by modulating the protein translation and degradation pathways. Yohimbine, an α2-adrenergic receptor antagonist, upregulated plasma NE and NGF expression by activating the protein translation and degradation pathways in naive rats. In contrast, a cocktail of adrenergic receptor antagonists suppressed the upregulation of NGF by blocking the activation of the protein translation and degradation pathways. Our findings provide evidence that the elevation of plasma NE induces NGF expression in the gastric fundus. PMID:26608656

  19. CD11b+Ly6G− myeloid cells mediate mechanical inflammatory pain hypersensitivity

    PubMed Central

    Ghasemlou, Nader; Chiu, Isaac M.; Julien, Jean-Pierre; Woolf, Clifford J.

    2015-01-01

    Pain hypersensitivity at the site of inflammation as a result of chronic immune diseases, pathogenic infection, and tissue injury is a common medical condition. However, the specific contributions of the innate and adaptive immune system to the generation of pain during inflammation have not been systematically elucidated. We therefore set out to characterize the cellular and molecular immune response in two widely used preclinical models of inflammatory pain: (i) intraplantar injection of complete Freund’s adjuvant (CFA) as a model of adjuvant- and pathogen-based inflammation and (ii) a plantar incisional wound as a model of tissue injury-based inflammation. Our findings reveal differences in temporal patterns of immune cell recruitment and activation states, cytokine production, and pain in these two models, with CFA causing a nonresolving granulomatous inflammatory response whereas tissue incision induced resolving immune and pain responses. These findings highlight the significant differences and potential clinical relevance of the incisional wound model compared with the CFA model. By using various cell-depletion strategies, we find that, whereas lymphocyte antigen 6 complex locus G (Ly)6G+CD11b+ neutrophils and T-cell receptor (TCR) β+ T cells do not contribute to the development of thermal or mechanical pain hypersensitivity in either model, proliferating CD11b+Ly6G− myeloid cells were necessary for mechanical hypersensitivity during incisional pain, and, to a lesser extent, CFA-induced inflammation. However, inflammatory (CCR2+Ly6Chi) monocytes were not responsible for these effects. The finding that a population of proliferating CD11b+Ly6G− myeloid cells contribute to mechanical inflammatory pain provides a potential cellular target for its treatment in wound inflammation. PMID:26598697

  20. A histamine release assay to identify sensitization to Culicoides allergens in horses with skin hypersensitivity.

    PubMed

    Wagner, Bettina; Childs, Bronwen A; Erb, Hollis N

    2008-12-15

    Skin hypersensitivity is an allergic disease induced in horses by allergens of Culicoides midges. The condition is typically diagnosed by clinical signs and in some horses in combination with allergy testing such as intradermal skin testing or serological allergen-specific IgE determination. Here, we describe an alternative method for allergy testing: a histamine release assay (HRA) that combines the functional aspects of skin testing with the convenience of submitting a blood sample. The assay is based on the principle that crosslinking of allergen-specific IgE bound via high-affinity IgE receptors to the surfaces of mast cells and basophils induces the release of inflammatory mediators. One of these mediators is histamine. The histamine was then detected by a colorimetric enzyme-linked immunosorbent assay. The histamine assay was used to test 33 horses with skin hypersensitivity and 20 clinically healthy control animals for histamine release from their peripheral blood basophils after stimulation with Culicoides allergen extract or monoclonal anti-IgE antibody. An increased histamine release was observed in the horses with skin hypersensitivity compared to the control group after allergen-specific stimulation with Culicoides extract (p=0.023). In contrast, stimulation with anti-IgE induced similar amounts of released histamine in both groups (p=0.46). For further evaluation of the HRA, we prepared a receiver operating-characteristic (ROC) curve and performed a likelihood-ratio analysis for assay interpretation. Our results suggested that the assay is a valuable diagnostic tool to identify sensitization to Culicoides allergens in horses. Because some of the clinically healthy horses also showed sensitization to Culicoides extract, the assay cannot be used to distinguish allergic from non-allergic animals. The observation that sensitization is sometimes detectable in non-affected animals suggested that clinically healthy horses use immune mechanisms to control the

  1. Human Telomeres Are Hypersensitive to UV-Induced DNA Damage and Refractory to Repair

    PubMed Central

    Rochette, Patrick J.; Brash, Douglas E.

    2010-01-01

    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. PMID:20442874

  2. Follow-up assessment of two cases of trichloroethylene hypersensitivity syndrome: A case report.

    PubMed

    Huang, Yong-Shun; Huang, Han-Lin; Wu, Qi-Feng; Xia, Li-Hua; Huang, Ming; Qiu, Xin-Xiang; Zhou, Shan-Yu

    2016-08-01

    The present study aimed to explore the stability, curability and sequelae of cases of Trichloroethylene (TCE) Hypersensitivity Syndrome (THS), and to investigate the causal allergens of THS. Two cases of THS were followed-up in the current study; both cases were healing following glucocorticoid therapy and were discharged >10 weeks prior to follow-up. A questionnaire investigation, health examination and patch test were performed. Allergens of TCE and its metabolites, including chloral hydrate, trichloroethanol (TCOH) and trichloroacetic acid, were applied in the patch test; 4 controls were included. The two subjects were experiencing itching, pigmentation and xerosis of the skin, and had abnormal results in the ophthalmology Schirmer I test and tear break-up time. The body temperature, liver function, superficial lymph nodes, blood, urine routine and autoimmune antibodies of two subjects were shown to be normal, and no new rashes had appeared. All mass concentration of chloral hydrate and TCOH were positive; 5.0% trichloroacetic acid was weakly positive, 0.5% trichloroacetic acid and all mass concentration of TCE were negative. All patch tests were negative in the 4 control subjects. The results suggest that THS was stable following treatment with glucocorticoid therapy. Dry eye syndrome may continue as a sequelae of THS. The patch test demonstrated that the mechanism underlying THS is delayed-type hypersensitivity induced by TCE. In addition, as the hypersensitivity state in a THS rehabilitee could be sustained over a long period of time, it suggests that the metabolites of TCE, not TCE itself, are responsible for THS. Therefore, patients with THS should avoid contact with TCE and its metabolites, and avoid using hypnotic and anticonvulsive drugs containing chloral hydra as the primary ingredient.

  3. Follow-up assessment of two cases of trichloroethylene hypersensitivity syndrome: A case report

    PubMed Central

    Huang, Yong-Shun; Huang, Han-Lin; Wu, Qi-Feng; Xia, Li-Hua; Huang, Ming; Qiu, Xin-Xiang; Zhou, Shan-Yu

    2016-01-01

    The present study aimed to explore the stability, curability and sequelae of cases of Trichloroethylene (TCE) Hypersensitivity Syndrome (THS), and to investigate the causal allergens of THS. Two cases of THS were followed-up in the current study; both cases were healing following glucocorticoid therapy and were discharged >10 weeks prior to follow-up. A questionnaire investigation, health examination and patch test were performed. Allergens of TCE and its metabolites, including chloral hydrate, trichloroethanol (TCOH) and trichloroacetic acid, were applied in the patch test; 4 controls were included. The two subjects were experiencing itching, pigmentation and xerosis of the skin, and had abnormal results in the ophthalmology Schirmer I test and tear break-up time. The body temperature, liver function, superficial lymph nodes, blood, urine routine and autoimmune antibodies of two subjects were shown to be normal, and no new rashes had appeared. All mass concentration of chloral hydrate and TCOH were positive; 5.0% trichloroacetic acid was weakly positive, 0.5% trichloroacetic acid and all mass concentration of TCE were negative. All patch tests were negative in the 4 control subjects. The results suggest that THS was stable following treatment with glucocorticoid therapy. Dry eye syndrome may continue as a sequelae of THS. The patch test demonstrated that the mechanism underlying THS is delayed-type hypersensitivity induced by TCE. In addition, as the hypersensitivity state in a THS rehabilitee could be sustained over a long period of time, it suggests that the metabolites of TCE, not TCE itself, are responsible for THS. Therefore, patients with THS should avoid contact with TCE and its metabolites, and avoid using hypnotic and anticonvulsive drugs containing chloral hydra as the primary ingredient. PMID:27446293

  4. Speech Discrimination Difficulties in High-Functioning Autism Spectrum Disorder Are Likely Independent of Auditory Hypersensitivity

    PubMed Central

    Dunlop, William A.; Enticott, Peter G.; Rajan, Ramesh

    2016-01-01

    Autism Spectrum Disorder (ASD), characterized by impaired communication skills and repetitive behaviors, 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. PMID:27555814

  5. Constructing a classification of hypersensitivity/allergic diseases for ICD-11 by crowdsourcing the allergist community.

    PubMed

    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.

  6. Cytokine overproduction and crosslinker hypersensitivity are unlinked in Fanconi anemia macrophages.

    PubMed

    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.

  7. Adrenergic denervation hypersensitivity in ileal circular smooth muscle after small bowel transplantation in rats.

    PubMed

    Shibata, C; Balsiger, B M; Anding, W J; Sarr, M G

    1997-11-01

    Effects of small bowel transplantation (SBT) on ileal motility are unknown. The aim of the present study was to investigate changes in spontaneous contractile activity and sensitivity to cholinergic and adrenergic agents in the ileal circular muscle after SBT in rats. Orthotopic SBT was performed in syngeneic rats to avoid immune phenomena. Distal ileal circular muscle strips from rats one week (N = 10) and eight weeks (N = 10) after SBT were stretched to optimal length (Lo), and basal spontaneous activity at Lo was measured. Dose-response experiments to the cholinergic agonist bethanechol (Be, 10(-8)-10(-4) M) were performed in the presence of tetrodotoxin (TTX, 10(-6) M) and to the adrenergic agonist norepinephrine (NE, 10(-8)-10(-4) M) with or without TTX. ED50 (negative log of drug-concentration that induced 50% effect) was calculated. We also studied rats with selective jejunoileal ischemia/ reperfusion, intestinal transection/reanastomosis, naive controls, and sham operated controls (N > or = 8/group). Spontaneous basal activity did not differ among groups. Sensitivity to Be was not different in rats after SBT or in other groups compared to control tissue. After SBT, hypersensitivity to NE was shown by a significant increase of ED50 at one and eight weeks after SBT (5.1 +/- 0.3 vs 6.2 +/- 0.4 and 6.2 +/- 0.2, respectively; P < 0.05) regardless of the presence of TTX. No hypersensitivity was observed after ischemia-reperfusion intestinal transection-reanastomosis, or sham operation. It is concluded that ileal hypersensitivity to NE was related to the extrinsic denervation obligated by the transplantation procedure, possibly mediated through an increase in number of receptors on smooth muscle, not on the enteric nerves.

  8. Practical Management of Patients with a History of Immediate Hypersensitivity to Common non-Beta-Lactam Drugs.

    PubMed

    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.

  9. Hippocampal microglial activation and glucocorticoid receptor down-regulation precipitate visceral hypersensitivity induced by colorectal distension in rats.

    PubMed

    Zhang, Gongliang; Zhao, Bing-Xue; Hua, Rong; Kang, Jie; Shao, Bo-Ming; Carbonaro, Theresa M; Zhang, Yong-Mei

    2016-03-01

    Visceral hypersensitivity is a common characteristic in patients suffering from irritable bowel syndrome (IBS) and other disorders with visceral pain. Although the pathogenesis of visceral hypersensitivity remains speculative due to the absence of pathological changes, the long-lasting sensitization in neuronal circuitry induced by early life stress may play a critical role beyond the digestive system even after complete resolution of the initiating event. The hippocampus integrates multiple sources of afferent inputs and sculpts integrated autonomic outputs for pain and analgesia regulation. Here, we examined the hippocampal mechanism in the pathogenesis of visceral hypersensitivity with a rat model induced by neonatal and adult colorectal distensions (CRDs). Neither neonatal nor adult CRD evoked behavioral abnormalities in adulthood; however, adult re-exposure to CRD induced persistent visceral hypersensitivity, depression-like behaviors, and spatial learning impairment in rats that experienced neonatal CRD. Rats that experienced neonatal and adult CRDs presented a decrease in hippocampal glucocorticoid receptor (GR) immunofluorescence staining and protein expression, and increases in hippocampal microglial activation and cytokine (IL-1β and TNF-α) accumulation. The decrease in hippocampal GR expression and increase in hippocampal IL-1β and TNF-α accumulation could be prevented by hippocampal local infusion of minocycline, a microglial inhibitor. These results suggest that neonatal CRD can increase the vulnerability of hippocampal microglia, and adult CRD challenge facilitates the hippocampal cytokine release from the sensitized microglia, which down-regulates hippocampal GR protein expression and, subsequently, precipitates visceral hypersensitivity.

  10. Oral antiplatelet agent hypersensitivity and cross-reactivity managed by successful desensitisation

    PubMed Central

    Rangamuwa, Kanishka; Mariasoosai, Raymond; Carnes, Jonathan; Thien, Francis

    2015-01-01

    Oral platelet aggregation inhibitors are widely used for the treatment and prevention of cardiovascular diseases, including coronary stent thrombosis. Premature discontinuation following percutaneous coronary intervention would pose a grave risk of in-stent thrombosis, acute myocardial infarction and eventual death. Although they share the same mechanism of adenosine diphosphate P2Y12 platelet receptor inhibition, they belong to either the chemical class of thienopyridines (clopidogrel, prasugrel, and ticlopidine) or cyclopentyl-triazolo-pyrimidines (ticagrelor and cangrelor). This case describes the first documented cross-reactive hypersensitivity of clopidogrel towards both its fellow thienopyridine, prasugrel, as well as the structurally dissimilar ticagrelor, and its subsequent successful desensitisation. PMID:25653921

  11. Equine allergy therapy: update on the treatment of environmental, insect bite hypersensitivity, and food allergies.

    PubMed

    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.

  12. [Selected clinical and laboratory tests during specific immunotherapy of patients hypersensitive to insect bites].

    PubMed

    Szymański, W; Kazberuk, M; Michalska, I; Chyrek-Borowska, S

    The study aimed at determining selected immunologic parameters of the cellular histamine secretion and skin reactivity in the group of 9 patients hypersensitive to insect poison with effective immunotherapy following 2 years of maintenance treatment. It has been shown that the continuation of the specific immunotherapy for 2 years maintains and even increases favourable changes in humoral and cellular immunity induced already in the early phase of desensitization. An assay of the specific IgE and IgG4, cellular histamine secretion, and skin reactivity is of value in monitoring specific allergy to insect poison immunotherapy.

  13. The Return of Delayed-Type Hypersensitivity Skin Testing for Coccidioidomycosis.

    PubMed

    Wack, Elizabeth E; Ampel, Neil M; Sunenshine, Rebecca H; Galgiani, John N

    2015-09-01

    A skin test that detects dermal hypersensitivity in persons with past infection with Coccidioides species is again available for clinical use. Nearly all of the clinical studies with similar materials were published prior to the 1990s, and as a result, many practicing physicians will be unfamiliar with how skin testing for coccidioidomycosis might be useful in patient management or as a research tool. We review clinical and epidemiological studies with past skin test antigens, the composition of past and current skin test preparations with particular attention to differences in the preservatives, and how the current preparation could be used today.

  14. Liver dysfunction induced by systemic hypersensitivity reaction to lamotrigine: case report.

    PubMed

    Im, Sung Gyu; Yoo, Sun Hong; Park, Young Min; Lee, Sang Jin; Jang, Sun Kyung; Jeon, Dong Ok; Cho, Hyo Jin; Oh, Mi Jung

    2015-06-01

    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.

  15. Bronchoscopic Investigation of Atypical Drug-induced Hypersensitivity Syndrome Showing Viral Lung Involvement.

    PubMed

    Hase, Isano; Arakawa, Hiroaki; Sakuma, Hideo; Kaneko, Fumio; Watanabe, Yuzuru; Fujiu, Koichi; Miyamoto, Hideaki; Ishii, Yoshiki

    We herein report a case of atypical drug-induced hypersensitivity syndrome (DIHS) involving serological reactivation of cytomegalovirus induced by carbamazepine with pulmonary and skin manifestations. These lesions were not present on admission, but developed on virus reactivation as indicated by the presence of inclusion bodies and multinucleated giant cells in alveolar cells with CD8(+) T lymphocyte infiltration on a transbronchial lung biopsy. Although the precise mechanism of DIHS remains unknown, this case suggests the crucial role of viral reactivation in pulmonary lesions in DIHS.

  16. [Impairment of social interaction, coordination disorder, and hypersensitivity in Asperger's syndrome].

    PubMed

    Asai, Tomoko; Sugiyam, Toshiro

    2007-03-01

    Asperger's syndrome is not accompanied with intellectual disability, however it has social impairments as well as autism and demonstrates failure to develop peer relationships according to each life stage. Social reciprocal behavior deficits are revealed typically during childhood. On the other hand, after school age these deficits are modified by environmental factors that may induce secondary disorders consequently. Hypersensitivity and coordination disorder, which are not included in diagnostic criteria for Asperger's syndrome, are often in presence. These symptoms are diminished and rarely interfere daily living as growth. However they may keep Asperger's syndrome individuals from adapting to others, so we need to take it into consideration.

  17. Prediction of hypersensitivity to antibiotics: what factors need to be considered?

    PubMed

    Ariza, Adriana; Fernández, Tahía D; Mayorga, Cristobalina; Blanca, Miguel; Torres, María José

    2013-12-01

    This review focuses on the epidemiology and different risk factors related to the development of hypersensitivity reactions to antibiotics, with a focus on betalactams and fluoroquinolones, the compounds most frequently involved in these reactions, due to their high level of consumption. The true prevalence of allergic drug reactions is unknown and the corresponding morbidity, mortality and associated economic costs are often underestimated. It is reported that multiple risk factors, related to both the drug and the patient, can modify the clinical expression of immune-mediated drug reactions. These include the chemical properties, molecular weight and administration route of the drug and the age, gender, concomitant diseases and genetic factors of the patient.

  18. Neonatal parenteral nutrition hypersensitivity: a case report implicating bisulfite sensitivity in a newborn infant.

    PubMed

    Huston, Robert K; Baxter, Louise M; Larrabee, Paige B

    2009-01-01

    This report describes a case of parenteral nutrition hypersensitivity in a 37 weeks' gestation infant with congenital diaphragmatic hernia complicated by bowel necrosis and functional short bowel syndrome. The patient developed a rash with subsequent urticaria beginning on the 50th day of life. The reactions were confirmed with a positive rechallenge. After the amino acid solution was replaced with a non-bisulfite-containing product, the infant was able to continue to receive nutrition support through parenteral nutrition without recurrence of symptoms. It is speculated that the bisulfite additive in the amino acid solution may have interacted with the lipid emulsion to sensitize the patient.

  19. Skin Testing in the Evaluation and Management of Carboplatin-Related Hypersensitivity Reactions.

    PubMed

    Lax, Timothy; Long, Aidan; Banerji, Aleena

    2015-01-01

    Carboplatin-induced hypersensitivity reactions (HSRs) are a frequent occurrence in patients being retreated for malignancy. The most common and severe reactions are thought to be IgE mediated. Currently, skin testing is the only method used clinically to identify individuals sensitized to carboplatin. Despite almost 20 years of clinical use, a standardized approach to skin testing and its use in the management of carboplatin HSRs has not been well established. We review the utility of carboplatin skin testing and discuss factors that influence the interpretation of skin testing results. A risk stratification strategy using skin testing and desensitization to manage patients with carboplatin HSRs is proposed.

  20. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans.

    PubMed

    Tamura, Akitoshi; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence.

  1. Hypersensitivity Vasculitis

    MedlinePlus

    ... most frequently listed as being associated with the development of HV include: penicillin, cephalosporin, sulfonamide, some medicines used to control blood pressure (loop and thiazide-type diuretics), phenytoin and allopurinol. Infections that may be ...

  2. Unexplained hypotension and exertional dyspnea in a night-cycled peritoneal dialysis patient--a rare form of icodextrin hypersensitivity.

    PubMed

    Onuigbo, Macaulay A C

    2014-01-01

    In recent years, icodextrin 7.5% has been used in PD as an alternative to glucose to achieve sustained reliable ultrafiltration (UF) and clearance without adversely increasing glucose absorption. Icodextrin is generally well tolerated. The most commonly reported adverse events are cutaneous reactions. We report a rare form of hypersensitivity to icodextrin 7.5% that was accompanied by dyspnea and symptomatic hypotension, without increased UF to account for the observed hypotension. Icodextrin produces symptomatic hypotension in up to 40% of patients by a known mechanism of increased UF and corresponding weight loss. However, it can also produce symptomatic hypotension accompanied by several other systemic symptoms in a hypersensitivity reaction. Discontinuation of the icodextrin results in prompt resolution of those symptoms. Treating nephrologists must be aware of this rare form of icodextrin hypersensitivity.

  3. Seven steps to the diagnosis of NSAIDs hypersensitivity: how to apply a new classification in real practice?

    PubMed

    Kowalski, Marek L; Makowska, Joanna S

    2015-07-01

    Frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) has been paralleled by increasing occurrence of adverse reactions, which vary from mild local skin rashes or gastric irritation to severe, generalized symptoms and even life-threatening anaphylaxis. NSAID-induced hypersensitivity reactions may involve both immunological and non-immunological mechanisms and should be differentiated from type A adverse reactions. Clinical diagnosis and effective management of a hypersensitive patient cannot be achieved without identifying the underlying mechanism. In this review, we discuss the current classification of NSAID-induced adverse reactions and propose a practical diagnostic algorithm that involves 7 steps leading to the determination of the type of NSAID-induced hypersensitivity and allows for proper patient management.

  4. Effects of active immunisation with myelin basic protein and myelin-derived altered peptide ligand on pain hypersensitivity and neuroinflammation.

    PubMed

    Perera, Chamini J; Lees, Justin G; Duffy, Samuel S; Makker, Preet G S; Fivelman, Brett; Apostolopoulos, Vasso; Moalem-Taylor, Gila

    2015-09-15

    Neuropathic pain is a debilitating condition in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Specific myelin basic protein (MBP) peptides are encephalitogenic, and myelin-derived altered peptide ligands (APLs) are capable of preventing and ameliorating EAE. We investigated the effects of active immunisation with a weakly encephalitogenic epitope of MBP (MBP87-99) and its mutant APL (Cyclo-87-99[A(91),A(96)]MBP87-99) on pain hypersensitivity and neuroinflammation in Lewis rats. MBP-treated rats exhibited significant mechanical and thermal pain hypersensitivity associated with infiltration of T cells, MHC class II expression and microglia activation in the spinal cord, without developing clinical signs of paralysis. Co-immunisation with APL significantly decreased pain hypersensitivity and neuroinflammation emphasising the important role of neuroimmune crosstalk in neuropathic pain.

  5. Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity

    PubMed Central

    Ye, Yi; Dang, Dongmin; Viet, Chi T.; Dolan, John C.; Schmidt, Brian L.

    2013-01-01

    Cancer patients often suffer from pain and most will be prescribed μ-opioids. μ-opioids are not satisfactory in treating cancer pain and are associated with multiple debilitating side effects. Recent studies show that μ and δ opioid receptors are separately expressed on IB4 (−) and IB4 (+) neurons which control thermal and mechanical pain, respectively. In this study we investigated IB4 (+) and IB4 (−) neurons in mechanical and thermal hypersensitivity in an orthotopic mouse oral cancer model. We used a δ opioid receptor agonist and a P2X3 antagonist to target IB4 (+) neurons and to demonstrate that this subset plays a key role in cancer-induced mechanical allodynia, but not in thermal hyperalgesia. Moreover, selective removal of IB4 (+) neurons using IB4-SAP impacts cancer-induced mechanical but not thermal hypersensitivity. Our results demonstrate that peripherally administered pharmacological agents targeting IB4 (+) neurons, such as a selective δ-opioid receptor agonist or P2X3 antagonist, might be useful in treating oral cancer pain. Perspective To clarify the mechanisms of oral cancer pain, we examined the differential role of IB4 (+) and IB4 (−) neurons. Characterization of these two subsets of putative nociceptors is important for further development of effective clinical cancer pain relief. PMID:22483679

  6. Talent in autism: hyper-systemizing, hyper-attention to detail and sensory hypersensitivity

    PubMed Central

    Baron-Cohen, Simon; Ashwin, Emma; Ashwin, Chris; Tavassoli, Teresa; Chakrabarti, Bhismadev

    2009-01-01

    We argue that hyper-systemizing predisposes individuals to show talent, and review evidence that hyper-systemizing is part of the cognitive style of people with autism spectrum conditions (ASC). We then clarify the hyper-systemizing theory, contrasting it to the weak central coherence (WCC) and executive dysfunction (ED) theories. The ED theory has difficulty explaining the existence of talent in ASC. While both hyper-systemizing and WCC theories postulate excellent attention to detail, by itself excellent attention to detail will not produce talent. By contrast, the hyper-systemizing theory argues that the excellent attention to detail is directed towards detecting ‘if p, then q’ rules (or [input–operation–output] reasoning). Such law-based pattern recognition systems can produce talent in systemizable domains. Finally, we argue that the excellent attention to detail in ASC is itself a consequence of sensory hypersensitivity. We review an experiment from our laboratory demonstrating sensory hypersensitivity detection thresholds in vision. We conclude that the origins of the association between autism and talent begin at the sensory level, include excellent attention to detail and end with hyper-systemizing. PMID:19528020

  7. Novel TRPM8 antagonist attenuates cold hypersensitivity after peripheral nerve injury in rats.

    PubMed

    Patel, Ryan; Gonçalves, Leonor; Newman, Robert; Jiang, Feng Li; Goldby, Anne; Reeve, Jennifer; Hendrick, Alan; Teall, Martin; Hannah, Duncan; Almond, Sarah; Brice, Nicola; Dickenson, Anthony H

    2014-04-01

    Abnormal cold sensitivity is a common feature of a range of neuropathies. In the murine somatosensory system, multiple aspects of cold sensitivity are dependent on TRPM8, both short term and in response to peripheral nerve injury. The specialized nature of cold-sensitive afferents and the restricted expression of TRPM8 render it an attractive target for the treatment of cold hypersensitivity. This current study examines the effect of a novel TRPM8 antagonist (M8-An) in naive and spinal nerve-ligated rats through behavioral and in vivo electrophysiological approaches. In vitro, M8-An inhibited icilin-evoked Ca(2+) currents in HEK293 cells stably expressing human TRPM8 with an IC(50) of 10.9 nM. In vivo, systemic M8-An transiently decreased core body temperature. Deep dorsal horn recordings were made in vivo from neurons innervating the hind paw. M8-An inhibited neuronal responses to innocuous and noxious cooling of the receptive field in spinal nerve-ligated rats but not in naive rats. No effect on neuronal responses to mechanical and heat stimulation was observed. In addition, M8-An also attenuated behavioral responses to cold but not mechanical stimulation after nerve ligation without affecting the uninjured contralateral response. The data presented here support a contribution of TRPM8 to the pathophysiology of cold hypersensitivity in this model and highlight the potential of the pharmacological block of TRPM8 in alleviating the associated symptoms.

  8. Evidence for a unique species-specific hypersensitive epitope in Mycobacterium tuberculosis derived cord factor.

    PubMed

    McMullen, Ashley M; Hwang, Shen-An; O'Shea, Kelly; Aliru, Maureen L; Actor, Jeffrey K

    2013-12-01

    Presensitization with Mtb-derived trehalose 6,6'-dimycolate (TDM; cord factor) followed by challenge with the same glycolipid species resulted in elicitation of stronger inflammatory responses than when mice were similarly challenged with M. bovis-derived TDM. Mice presensitized to the homologous Mtb-derived TDM demonstrated cachexic over a 6 day period, whereas similarly presensitized mice challenged with the M. bovis-derived TDM, or with emulsion control, did not experience weight loss. Examination of inflammatory responses demonstrated increased lung histopathology in the Mtb-derived TDM challenged group, evidenced by severe tissue disruption, cellular influx, vascular occlusion and lymphocytic cuffing, and endothelial cell damage. Histological analysis demonstrated that lung pathology in the M. bovis challenged group was strikingly similar to that of the acute model challenge. Examination of proinflammatory mediators also showed findings consistent with histological manifestation, with significantly elevated TNF-α and IL-1β, as well as IFN-γ, in the homologous TDM challenged group relative to all other groups. Overall, these findings indicate a difference in hypersensitive immune responses to TDM derived from different mycobacterial strains. Development of specific adaptive immune responses to the Mtb-derived TDM were demonstrated that had limited cross-reactivity to that of M. bovis, thus strongly suggesting the presence of hypersensitive epitopes exclusive to Mtb TDM not present on M. bovis-derived TDM.

  9. [Sodium cromoglycate in the treatment of food hypersensitivity in children under 3 years of age].

    PubMed

    Zur, E; Kaczmarski, M

    2001-09-01

    Dietary elimination is a treatment of first choice in food hypersensitivity. Such therapy is not always enough to stop the disease and introduction of pharmacological treatment is necessary. In prevention and long term treatment antiallergic drugs are recommended. The aim of the study was to assess efficacy and safety of oral sodium cromoglycate in treatment of food hypersensitivity in the youngest children. In our study we examined: the group of 25 children aged 6 months-3 years treated with oral cromolyn sodium during the period 4-20 weeks and 29 children aged 6 months-3 years treated with ketotifen. Symptoms from skin, digestive and respiratory tract, behaviour status were evaluated for drugs efficacy. Cromolyn and ketotifen effected a significant decrease in total symptoms score. The treatment was well tolerated. No serious side effects were noted. The incidents of skin rash, disquiet during the night, diarrhoea and urticaria were only 8 percent. Sodium cromoglycate is safe and effective drug in treatment of food allergy in children; specially in symptoms from gastrointestinal tract and multi-organs allergy.

  10. Global classification and coding of hypersensitivity diseases - An EAACI - WAO survey, strategic paper and review.

    PubMed

    Demoly, P; Tanno, L K; Akdis, C A; Lau, S; Calderon, M A; Santos, A F; Sanchez-Borges, M; Rosenwasser, L J; Pawankar, R; Papadopoulos, N G

    2014-05-01

    Hypersensitivity diseases are not adequately coded in the International Coding of Diseases (ICD)-10 resulting in misclassification, leading to low visibility of these conditions and general accuracy of official statistics. To call attention to the inadequacy of the ICD-10 in relation to allergic and hypersensitivity diseases and to contribute to improvements to be made in the forthcoming revision of ICD, a web-based global survey of healthcare professionals' attitudes toward allergic disorders classification was proposed to the members of European Academy of Allergy and Clinical Immunology (EAACI) (individuals) and World Allergy Organization (WAO) (representative responding on behalf of the national society), launched via internet and circulated for 6 week. As a result, we had 612 members of 144 countries from all six World Health Organization (WHO) global regions who answered the survey. ICD-10 is the most used classification worldwide, but it was not considered appropriate in clinical practice by the majority of participants. The majority indicated the EAACI-WAO classification as being easier and more accurate in the daily practice. They saw the need for a diagnostic system useful for nonallergists and endorsed the possibility of a global, cross-culturally applicable classification system of allergic disorders. This first and most broadly international survey ever conducted of health professionals' attitudes toward allergic disorders classification supports the need to update the current classifications of allergic diseases and can be useful to the WHO in improving the clinical utility of the classification and its global acceptability for the revised ICD-11.

  11. Ranking of parameters of pain hypersensitivity according to their discriminative ability in chronic low back pain.

    PubMed

    Neziri, Alban Y; Curatolo, Michele; Limacher, Andreas; Nüesch, Eveline; Radanov, Bogdan; Andersen, Ole K; Arendt-Nielsen, Lars; Jüni, Peter

    2012-10-01

    Low back pain is associated with plasticity changes and central hypersensitivity in a subset of patients. We performed a case-control study to explore the discriminative ability of different quantitative sensory tests in distinguishing between 40 cases with chronic low back pain and 300 pain-free controls, and to rank these tests according to the extent of their association with chronic pain. Gender, age, height, weight, body mass index, and psychological measures were recorded as potential confounders. We used 26 quantitative sensory tests, including different modalities of pressure, heat, cold, and electrical stimulation. As measures of discrimination, we estimated receiver operating characteristics (ROC) and likelihood ratios. Six tests seemed useful (in order of their discriminative ability): (1) pressure pain detection threshold at the site of most severe pain (fitted area under the ROC, 0.87), (2) single electrical stimulation pain detection threshold (0.87), (3) single electrical stimulation reflex threshold (0.83), (4) pressure pain tolerance threshold at the site of most severe pain (0.81), (5) pressure pain detection threshold at suprascapular region (0.80), and (6) temporal summation pain threshold (0.80). Pressure and electrical pain modalities seemed most promising and may be used for diagnosis of pain hypersensitivity and potentially for identifying individuals at risk of developing chronic low back pain over time.

  12. Pretreatment with glycomacropeptide reduces allergen sensitization, alleviates immediate cutaneous hypersensitivity and protects from anaphylaxis

    PubMed Central

    Jiménez, M; Chávez, N A; Salinas, E

    2012-01-01

    Allergic disorders are characterized by the involvement of allergen-specific immunoglobulin (Ig)E antibodies and T helper type 2 (Th2) cells. The search for new therapies for allergic diseases has been the primary focus of interest for many investigators in recent years. Glycomacropeptide (GMP) is a biologically active component of milk that exhibits a range of immunomodulatory functions. We examined whether oral administration of GMP could affect the development of allergic sensitization and the severity of immediate cutaneous hypersensitivity reactions and of anaphylaxis. Rats treated with or without GMP were ovalbumin (OVA)-sensitized and several indicators of allergy were evaluated. Pretreatment with GMP resulted in reduction of antigen-specific IgE titre in rats when sensitized with OVA. GMP administration also markedly suppressed the proliferative response of splenocytes to antigen and the production of interleukin (IL)-13 by splenocytes of sensitized animals. In addition, GMP pretreatment attenuated the intensity of the immediate cutaneous reaction induced by antigen and protected the sensitized rats from severe anaphylaxis. These data demonstrate, for the first time, that the administration of GMP prevents allergen sensitization and reduces the severity of the early-phase reaction induced by antigen in cutaneous hypersensitivity and in anaphylaxis. GMP may be used as a novel prophylactic agent for the control of allergic diseases. PMID:22943197

  13. Brown coal derived humate inhibits contact hypersensitivity; An efficacy, toxicity and teratogenicity study in rats

    SciTech Connect

    Van Rensburg, C.E.J.; Snyman, J.R.; Mokoele, T.; Cromarty, A.D.

    2007-10-15

    The effects of two humate products were compared to that of prednisolone on a contact hypersensitivity rat model. Rats, sensitized with dinitrofluorobenzene (DNFB), were placed on a daily oral treatment of 61 mg/kg BW of humate derived from either leonardite or bituminous coal or on prednisolone at one mg/kg BW and challenged 6 days later with a topical application of DNFB to the right ear. The inflamed ears were measured daily. In a toxicity study rats were exposed to daily oral treatment of leonardite humate at 1,000 mg/kg BW for 1 month. A teratogenicity study was done where pregnant rats were treated with 500 mg/kg BW on days 5 to 17 of pregnancy. Only the leonardite humate compared favourably with prednisolone in suppressing contact hypersensitivity. No signs of toxicity were observed and weight gain was normal during the 6-day and 1 month treatments and during the teratogenicity study with the leonardite humate. However, the rats on the other two products experienced slower weight gain. The identification of a naturally occurring nontoxic compound with anti-inflammatory activity is exciting and merits further evaluation in the treatment of patients suffering from inflammatory conditions.

  14. Cytotoxicity of DP-bioglass paste used for treatment of dentin hypersensitivity.

    PubMed

    Kuo, Tien-Chun; Lee, Bor-Shiunn; Kang, Shu-Han; Lin, Feng-Huei; Lin, Chun-Pin

    2007-04-01

    DP-bioglass mixed with 30% phosphoric acid has been suggested to treat dentin hypersensitivity because the material is able to produce homogeneous occlusion of exposed dentinal tubules and is able to provide a sealing depth of up to 60 microm. The purpose of this study was to investigate the relative cytotoxic effect of the DP-bioglass paste, intermediate restorative material (IRM; DeTrey, Dentsply, Germany), and commercial desensitizing agent (Abmindent; Abmin Technologies Ltd, Turku, Finland) on human dental pulp cells by using a transwell insert model and a dentin-disc model. Cell viability was measured by means of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results of this study indicated that cell viability for the DP-bioglass paste did not differ significantly from those of the IRM or Abmindent in the transwell insert model. In addition, MTT results of DP-bioglass paste were similar to the control group in the dentin-disc model. The results indicated that DP-bioglass paste was a highly biocompatible material and could potentially serve as an effective material for treatment of dentin hypersensitivity.

  15. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2011.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2012-01-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2011. Food allergy appears to be increasing in prevalence and carries a strong economic burden. Risk factors can include dietary ones, such as deficiency of vitamin D and timing of complementary foods, and genetic factors, such as filaggrin loss-of-function mutations. Novel mechanisms underlying food allergy include the role of invariant natural killer T cells and influences of dietary components, such as isoflavones. Among numerous preclinical and clinical treatment studies, promising observations include the efficacy of sublingual and oral immunotherapy, a Chinese herbal remedy showing promising in vitro results, the potential immunotherapeutic effects of having children ingest foods with baked-in milk if they tolerate it, and the use of anti-IgE with or without concomitant immunotherapy. Studies of allergic skin diseases, anaphylaxis, and hypersensitivity to drugs and insect venom are elucidating cellular mechanisms, improved diagnostics, and potential targets for future treatment. The role of skin barrier abnormalities, as well as the modulatory effects of the innate and adaptive immune responses, are major areas of investigation.

  16. Pathogenesis and clinical approaches to anticonvulsant hypersensitivity syndrome: current state of knowledge.

    PubMed

    Scaparrotta, A; Verrotti, A; Consilvio, N P; Cingolani, A; Di Pillo, S; Di Gioacchino, M; Verini, M; Chiarelli, F

    2011-01-01

    Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but severe and potentially fatal, adverse reaction that occurs in patients who are treated with commonly used older anticonvulsant drugs (phenytoin, carbamazepine and phenobarbital) and/or with some newer agents (lamotrigine). Paediatric patients are at an increased risk for the development of AHS for the higher incidence of seizure disorder in the first decade of life. Hypersensitivity reactions range from simple maculopapular skin eruptions to a severe life-threatening disorder. AHS is typically associated with the development of skin rash, fever and internal organ dysfunctions. Recent evidence suggests that AHS is the result of a chemotoxic and immunologically-mediated injury, characterized by skin and mucosal bioactivation of antiepileptic drugs and by major histocompatibility complex-dependent clonal expansion of T cells. Early recognition of AHS and withdrawal of anticonvulsant therapy are essential for a successful outcome. In vivo and vitro tests can be helpful for the diagnosis that actually depends essentially on clinical recognition.

  17. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2010.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2011-02-01

    This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported in the Journal in 2010. Key epidemiologic observations include an apparent increase in peanut allergy, with more than 1% of children affected, and increasing evidence that early food allergen exposure, rather than avoidance, might improve allergy outcomes. Advances in food allergy diagnosis include improved insights into prognosis and estimation of severity through component-resolved diagnostics and characterization of IgE binding to specific epitopes. Regarding treatment, oral and epicutaneous immunotherapy show promise. Studies of drug allergies show insights into pathophysiology, and studies on insect hypersensitivity reveal improved diagnostic methods. Genetic and functional studies have revealed the important role of epidermal differentiation products in the pathogenesis of atopic dermatitis. Cross-talk between the atopic immune response with the innate immune response have also been found to predispose to infection in patients with atopic dermatitis. New therapeutic approaches to control chronic urticaria have also been identified during the past year.

  18. Hypersensitivity reactions to non-betalactam antibiotics in children: an extensive review.

    PubMed

    Kuyucu, Semanur; Mori, Francesca; Atanaskovic-Markovic, Marina; Caubet, Jean-Christoph; Terreehorst, Ingrid; Gomes, Eva; Brockow, Knut

    2014-10-01

    In contrast to hypersensitivity reactions (HSRs) to β-lactam antibiotics in children, studies about HSR to non-β-lactam antibiotics (NBLAs) such as sulfonamides, macrolides, quinolones, and antituberculosis agents are scarce, and information is generally limited to case reports. The aim of this extensive review was to summarize our present knowledge on clinical characteristics, evaluation, and management of HSR to NBLAs in children based on the literature published between 1980 and 2013. NBLAs have been reported to induce a wide spectrum of HSRs from mild eruptions to severe, and sometimes fatal, systemic drug reactions, especially in some high-risk groups. The diagnosis relied upon history and remained unconfirmed by allergological tests in most of the cases. Obtaining a detailed history is valuable in the diagnosis of suspected reactions to NBLAs. Diagnostic in vivo and in vitro tests for NBLAs lack validation, which makes the diagnosis challenging. The definitive diagnosis of NBLA hypersensitivity frequently depends upon drug provocation tests. Studies including children showed that only 7.8 to 36% of suspected immediate and delayed HSRs to NBLAs could be confirmed by skin and/or provocation tests. Therefore, a standardized diagnostic approach and management strategy should be developed and employed for pediatric patients in the evaluation of suspected HSRs to NBLAs, some of which may be critical and unreplaceable in certain clinical situations.

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

    PubMed Central

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

    2015-01-01

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

  20. Desensitizing treatments for dentin hypersensitivity: a randomized, split-mouth clinical trial.

    PubMed

    Camilotti, Veridiana; Zilly, Juliana; Busato, Priscilla do Monte Ribeiro; Nassar, Carlos Augusto; Nassar, Patrícia Oehlmeyer

    2012-01-01

    The aim of this randomized, controlled, split-mouth, clinical study was to differentiate and clinically qualify the effectiveness of different desensitizing agents in the treatment of painful symptoms caused by cervical dentin hypersensitivity (CDH). Two hundred-and-fifty-two teeth of 42 patients were distributed into seven groups (n = 36): G1 - placebo; G2, G3, G4 and G6 - fluoride varnishes; G5 - sodium fluoride; G7 - potassium oxalate. Three applications were made one week apart. A three-score system (Alfa = 0, Bravo = 2, and Charlie = 3, respectively for no sensitivity, slight sensitivity and high sensitivity) was used to assess CDH after each application and after 30 days. The data were subjected to statistical analysis using the Kruskall-Wallis and Dun tests. After the second week, statistically significant differences were observed for all materials compared with the baseline. After 30 days, Group G7 had presented a significant gradual reduction along all the evaluated time intervals. It was concluded that all the desensitizing agents were capable of reducing dentin hypersensitivity, with the exception of the placebo and the sodium fluoride groups.

  1. Transcriptomic analysis of Prunus domestica undergoing hypersensitive response to plum pox virus infection.

    PubMed

    Rodamilans, Bernardo; San León, David; Mühlberger, Louisa; Candresse, Thierry; Neumüller, Michael; Oliveros, Juan Carlos; García, Juan Antonio

    2014-01-01

    Plum pox virus (PPV) infects Prunus trees around the globe, posing serious fruit production problems and causing severe economic losses. One variety of Prunus domestica, named 'Jojo', develops a hypersensitive response to viral infection. Here we compared infected and non-infected samples using next-generation RNA sequencing to characterize the genetic complexity of the viral population in infected samples and to identify genes involved in development of the resistance response. Analysis of viral reads from the infected samples allowed reconstruction of a PPV-D consensus sequence. De novo reconstruction showed a second viral isolate of the PPV-Rec strain. RNA-seq analysis of PPV-infected 'Jojo' trees identified 2,234 and 786 unigenes that were significantly up- or downregulated, respectively (false discovery rate; FDR≤0.01). Expression of genes associated with defense was generally enhanced, while expression of those related to photosynthesis was repressed. Of the total of 3,020 differentially expressed unigenes, 154 were characterized as potential resistance genes, 10 of which were included in the NBS-LRR type. Given their possible role in plant defense, we selected 75 additional unigenes as candidates for further study. The combination of next-generation sequencing and a Prunus variety that develops a hypersensitive response to PPV infection provided an opportunity to study the factors involved in this plant defense mechanism. Transcriptomic analysis presented an overview of the changes that occur during PPV infection as a whole, and identified candidates suitable for further functional characterization.

  2. Steric gate variants of UmuC confer UV hypersensitivity on Escherichia coli.

    PubMed

    Shurtleff, Brenna W; Ollivierre, Jaylene N; Tehrani, Mohammad; Walker, Graham C; Beuning, Penny J

    2009-08-01

    Y family DNA polymerases are specialized for replication of damaged DNA and represent a major contribution to cellular resistance to DNA lesions. Although the Y family polymerase active sites have fewer contacts with their DNA substrates than replicative DNA polymerases, Y family polymerases appear to exhibit specificity for certain lesions. Thus, mutation of the steric gate residue of Escherichia coli DinB resulted in the specific loss of lesion bypass activity. We constructed variants of E. coli UmuC with mutations of the steric gate residue Y11 and of residue F10 and determined that strains harboring these variants are hypersensitive to UV light. Moreover, these UmuC variants are dominant negative with respect to sensitivity to UV light. The UV hypersensitivity and the dominant negative phenotype are partially suppressed by additional mutations in the known motifs in UmuC responsible for binding to the beta processivity clamp, suggesting that the UmuC steric gate variant exerts its effects via access to the replication fork. Strains expressing the UmuC Y11A variant also exhibit decreased UV mutagenesis. Strikingly, disruption of the dnaQ gene encoding the replicative DNA polymerase proofreading subunit suppressed the dominant negative phenotype of a UmuC steric gate variant. This could be due to a recruitment function of the proofreading subunit or involvement of the proofreading subunit in a futile cycle of base insertion/excision with the UmuC steric gate variant.

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

    PubMed

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

    2012-03-01

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

  4. Immune responses to ectoparasites of horses, with a focus on insect bite hypersensitivity.

    PubMed

    Wilson, A D

    2014-11-01

    Horses are affected by a wide variety of arthropod ectoparasites, ranging from lice which spend their entire life on the host, through ticks which feed over a period of days, to numerous biting insects that only transiently visit the host to feed. The presence of ectoparasites elicits a number of host responses including innate inflammatory responses, adaptive immune reactions and altered behaviour; all of which can reduce the severity of the parasite burden. All of these different responses are linked through immune mechanisms mediated by mast cells and IgE antibodies which have an important role in host resistance to ectoparasites, yet immune responses also cause severe pathological reactions. One of the best described examples of such pathological sequelae is insect bite hypersensitivity (IBH) of horses; an IgE-mediated type 1 hypersensitivity to the salivary proteins of Culicoides spp. associated with T-helper-2 production of IL4 and IL13. Importantly, all horses exposed to Culicoides have an expanded population of Culicoides antigen-specific T cells with this pattern of cytokine production, but in those which remain healthy, the inflammatory reaction is tempered by the presence of FoxP3+ CD4+ regulatory T cells that express IL10 and TGF-beta, which suppresses the IL4 production by Culicoides antigen-activated T cells.

  5. Occupational trichloroethylene hypersensitivity syndrome with human herpesvirus-6 and cytomegalovirus reactivation.

    PubMed

    Watanabe, Hideaki; Tohyama, Mikiko; Kamijima, Michihiro; Nakajima, Tamie; Yoshida, Takemi; Hashimoto, Koji; Iijima, Masafumi

    2010-08-01

    Patients having a generalised rash with severe liver dysfunction associated with exposure to trichloroethylene (TCE) have been reported mainly in Asian countries. However, no case has been reported in Japan since the 1990s. Here, we describe a case of hypersensitivity syndrome (HS) caused by TCE in a 30-year-old Japanese man. The patient developed a rash, fever and liver dysfunction 21 days after he had been exposed to TCE at his workplace. Serum human herpesvirus (HHV)-6 and cytomegalovirus (CMV) DNA were detected 4 and 7 weeks, respectively, after the onset; the IgG antibody titres to HHV-6 and CMV were significantly elevated 6 and 9 weeks, respectively, after the onset. Patch testing was positive for the metabolites of TCE (i.e. trichloroethanol, trichloroacetic acid and chloral hydrate) but not for TCE itself; these results suggest that the TCE metabolites induced this disease. Human leucocyte antigen-B*1301, which has been reported to be strongly associated with TCE-induced HS, was identified in this patient. In addition, the clinical findings, laboratory data and period of virus reactivation after onset were quite similar to those of drug-induced hypersensitivity syndrome (DIHS). We also review TCE-induced HS from the viewpoint of the similarity to DIHS in this article.

  6. Skin-prick tests for hypersensitivity to alpha-amylase preparations.

    PubMed

    Moneo, I; Alday, E; Sanchez-Agudo, L; Curiel, G; Lucena, R; Calatrava, J M

    1995-06-01

    Twenty-five asthmatic subjects with suspected alpha-amylase hypersensitivity were studied by skin-prick tests, a capture ELISA, immunoblotting and bronchial provocation tests. At the same time, different amylases were analysed by SDS-PAGE and immunoblotting using a polyclonal rabbit antiserum. Eight patients showed a positive bronchial response to amylase. Seven of them had positive skin-prick tests, with this method being the most sensitive approach for diagnosis. However, in four cases, skin tests were also positive although the patients had a negative provocation test, thus demonstrating that skin tests are not specific. ELISA and blotting showed similar results in terms of sensitivity and specificity. The enzymes used by the workers included several antigens besides alpha-amylase. The rabbit antiserum to alpha-amylase detected a protein in a wheat flour extract. In one case, the IgE antibodies were specific only for a contaminant of lower molecular weight than amylase. These facts suggest that proteins from the culture medium could be responsible for some cases of amylase hypersensitivity, making the diagnosis difficult. The presence of amylase in another enzymatic extract, a protease produced by Aspergillus oryzae, was proved by means of skin tests and immunoblotting, thus demonstrating the allergenic properties of this enzymatic preparation.

  7. An Arabidopsis mutant hypersensitive to red and far-red light signals.

    PubMed Central

    Genoud, T; Millar, A J; Nishizawa, N; Kay, S A; Schäfer, E; Nagatani, A; Chua, N H

    1998-01-01

    A new mutant called psi2 (for phytochrome signaling) was isolated by screening for elevated activity of a chlorophyll a/b binding protein-luciferase (CAB2-LUC) transgene in Arabidopsis. This mutant exhibited hypersensitive induction of CAB1, CAB2, and the small subunit of ribulose-1,5-bisphosphate carboxylase (RBCS) promoters in the very low fluence range of red light and a hypersensitive response in hypocotyl growth in continuous red light of higher fluences. In addition, at high- but not low-light fluence rates, the mutant showed light-dependent superinduction of the pathogen-related protein gene PR-1a and developed spontaneous necrotic lesions in the absence of any pathogen. Expression of genes responding to various hormone and environmental stress pathways in the mutant was not significantly different from that of the wild type. Analysis of double mutants demonstrated that the effects of the psi2 mutation are dependent on both phytochromes phyA and phyB. The mutation is recessive and maps to the bottom of chromosome 5. Together, our results suggest that PSI2 specifically and negatively regulates both phyA and phyB phototransduction pathways. The induction of cell death by deregulated signaling pathways observed in psi2 is reminiscent of retinal degenerative diseases in animals and humans. PMID:9634578

  8. Drug-reaction eosinophilia and systemic symptoms and drug-induced hypersensitivity syndrome.

    PubMed

    Fernando, Suran L

    2014-02-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a rare, severe cutaneous adverse reaction characterised by fever, rash, lymphadenopathy, eosinophilia and/or other leukocyte abnormalities, and internal organ involvement and often has a relapsing-remitting course despite withdrawal of the drug. The drugs that are most implicated include aromatic anticonvulsants, allopurinol, sulphonamides, antiretrovirals (abacavir and nevirapine), and minocycline. The pathogenesis of DRESS/DIHS is far from clear but probably involves a combination of impaired pharmacokinetics and the accumulation of drug metabolites, the sequential reactivation of the herpesvirus family and genetic susceptibility conferred by the association with certain human leukocyte antigen (HLA) class I alleles. The strong association between abacavir and HLA-B*5701 has enabled pharmacogenetics screening to be employed successfully to minimise the occurrence of hypersensitivity. A prolonged course of oral corticosteroids is required to treat DRESS/DIHS, given the relapsing-remitting nature of the condition with i.v. immunoglobulin and valgangciclovir reserved for refractory or life-threatening cases.

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

    NASA Astrophysics Data System (ADS)

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

    2010-11-01

    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.

  10. Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management

    PubMed Central

    Rampton, David; Folkersen, Joergen; Fishbane, Steven; Hedenus, Michael; Howaldt, Stefanie; Locatelli, Francesco; Patni, Shalini; Szebeni, Janos; Weiss, Guenter

    2014-01-01

    Intravenous iron is widely used for the treatment of iron deficiency anemia when oral iron is inappropriate, ineffective or poorly tolerated. Acute hypersensitivity reactions during iron infusions are very rare but can be life-threatening. This paper reviews their frequency, pathogenesis and risk factors, and provides recommendations about their management and prevention. Complement activation-related pseudo-allergy triggered by iron nanoparticles is probably a more frequent pathogenetic mechanism in acute reactions to current formulations of intravenous iron than is an immunological IgE-mediated response. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, severe atopy, and possibly systemic inflammatory diseases. Early pregnancy is a contraindication to iron infusions, while old age and serious co-morbidity may worsen the impact of acute reactions if they occur. Management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff. PMID:25420283

  11. In vitro efficacy of a novel potassium oxalate hydrogel for dentin hypersensitivity.

    PubMed

    Varoni, Elena M; Zuccheri, Tommaso; Carletta, Andrea; Palazzo, Barbara; Cochis, Andrea; Colonna, Martino; Rimondini, Lia

    2017-04-01

    A novel potassium oxalate-based hydrogel is proposed for treating dentin hypersensitivity and this study evaluates its in vitro performance as a remineralizing, desensitizing agent. Etched disks of human dentin were treated for 10 or 20 min using the test hydrogel, to mimic a professional application with dental mouth guards. Dentin disks were evaluated in terms of permeability indexes in a fluid-filled system, the surface morphology was assessed by scanning electron microscopy, and the structural properties were studied using X-ray diffraction analysis. The potassium oxalate hydrogel significantly reduced dentin permeability, in a time-dependent manner, and occluded most of the patent dentinal tubules via crystal precipitation, forming a remineralized layer. After hydrogel treatments, an acid solution (pH 4.2) was applied to the disks for 30 s, or 1, 2, or 5 min, in order to reproduce a plaque-like oral acidity, and further analysis showed a good resistance of the remineralized layer to the acid challenge. The potassium oxalate-based hydrogel showed a better performance over commercially available products and artificial saliva, appearing a promising candidate for the treatment of dentin hypersensitivity.

  12. Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity.

    PubMed

    Watanabe, Hideki; Gaide, Olivier; Pétrilli, Virginie; Martinon, Fabio; Contassot, Emmanuel; Roques, Stéphanie; Kummer, Jean A; Tschopp, Jürg; French, Lars E

    2007-08-01

    The inflammasome is a cytosolic protein complex regulating the activation of caspase-1, which cleaves the pro-inflammatory cytokines IL-1beta and IL-18 into their active form. The inflammasome is composed of a NACHT-, LRR- and pyrin (NALP) family member that acts as a sensor for danger signals and the adaptor protein apoptosis-associated speck-like protein containing a CARD domain (ASC), which allows the recruitment of caspase-1 in the complex. In the skin, exposure to contact sensitizers (CS) such as trinitro-chlorobenzene causes an immune response called contact hypersensitivity (CHS) or eczema. In this delayed-type hypersensitivity response, efficient priming of the adaptive immunity depends on the concomitant activation of the innate immune system, including IL-1beta/IL-18 activation in the skin. To determine if the inflammasome contributes to CHS, we have analyzed its capacity to react to CS in vitro and in vivo. We show here that key components of the inflammasome are present in human keratinocytes and that CS like trinitro-chlorobenzene induce caspase-1/ASC dependent IL-1beta and IL-18 processing and secretion. We also show that ASC- and NALP3-deficient mice display an impaired response to CS. These findings suggest that CS act as danger signals that activate the inflammasome in the skin, and reveal a new role of NALP3 and ASC as regulators of innate immunity in CHS.

  13. Hypersensitivity of human subjects to environmental electric and magnetic field exposure: a review of the literature.

    PubMed Central

    Levallois, Patrick

    2002-01-01

    Hypersensitivity to exposure to electric and magnetic fields (EMFs) has been reported for nearly 20 years; however, the literature on the subject is still very limited. Nearly all the literature published concerns a dermatological syndrome that consists of mainly subjective symptoms (itching, burning, dryness) and a few objective symptoms (redness, dryness) appearing after individuals begin working with video display units and decreasing during absence from work. Case-control studies as well as some good but limited double-blind trials have not found any clear relationship between this syndrome and exposure to EMFs. A "general syndrome" with more general symptoms has been rarely described but seems to have a worse prognosis. The symptoms often associated with skin disorders are mainly of neurasthenic type and can cover a lot of nonspecific symptoms present in other atypical syndromes such as multiple chemical sensitivity or chronic fatigue. Most of these symptoms are allegedly triggered by exposure to different sources of EMFs, but there have been no valid etiological studies published on this more general syndrome. It appears that the so-called hypersensitivity to environmental electric and magnetic fields is an unclear health problem whose nature has yet to be determined. PMID:12194895

  14. Small bowel transplantation induces adrenergic hypersensitivity in ileal longitudinal smooth muscle in rats.

    PubMed

    Ohtani, N; Balsiger, B M; Anding, W J; Duenes, J A; Sarr, M G

    2000-01-01

    Our aim was to determine the effects of small bowel transplantation on contractility of longitudinal muscle in the rat ileum. Full-thickness longitudinal muscle strips from four groups of rats (naive controls, sham-operated controls, and 1 week and 8 weeks after syngeneic orthotopic small bowel transplantation) were studied in vitro. Neither baseline contractility nor response to neural blockade (tetrodotoxin) or adrenergic/cholinergic blockade differed among the groups. Although the dose response to the cholinergic agonist bethanechol and to nitric oxide did not differ among groups, the ED50 (negative log of concentration giving half-maximal effect) for the adrenergic agonist norepinephrine was increased l week and 8 weeks after transplantation, indicating a hypersensitivity response not blocked by tetrodotoxin. Nonadrenergic, noncholinergic inhibitory responses to electrical field stimulation were of greater amplitude and occurred at lesser frequencies (>/=5 Hz) 1 week after small bowel transplantation, but returned to control values 8 weeks postoperatively. These inhibitory responses were blocked by the nitric oxide synthase inhibitor L-NMMA but not by methylene blue, a nonspecific inhibitor of guanylate cyclase. Small bowel transplantation induces a persistent adrenergic denervation hypersensitivity at the muscle and appears to upregulate, at least transiently, other inhibitory mechanisms mediated by neural release of nitric oxide. Small bowel transplantation does not alter muscle response to cholinergic pathways. These alterations in smooth muscle contractility may affect gut function early after clinical small bowel transplantation.

  15. Gastroesophageal reflux symptoms not responding to proton pump inhibitor: GERD, NERD, NARD, esophageal hypersensitivity or dyspepsia?

    PubMed

    Bashashati, Mohammad; Hejazi, Reza A; Andrews, Christopher N; Storr, Martin A

    2014-06-01

    Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy.

  16. Immediate systemic hypersensitivity reaction associated with topical application of Australian tea tree oil.

    PubMed

    Mozelsio, Nancy B; Harris, Kathleen E; McGrath, Kris G; Grammer, Leslie C

    2003-01-01

    Australian tea tree oil has been used as a veterinary antiseptic for many years and, more recently, has been extended into human use. There have been many reports of allergic contact dermatitis and toxicity reactions, but it has never been implicated in immediate systemic hypersensitivity reactions. A 38-year-old man experienced immediate flushing, pruritus, throat constriction, and lightheadedness after topical application of tea tree oil. Our purpose was to determine whether this represented an immunoglobulin E (IgE)--mediated reaction. Skin-prick and intradermal testing was performed, as well as enzyme-linked immunosorbent assays for specific IgG and IgE against tea tree oil. The patient had a positive wheal and flare reaction on intradermal testing with tea tree oil. All five patient controls were negative on skin testing. No specific IgG or IgE was detected. We present the first reported case of an immediate systemic hypersensitivity reaction occurring after topical application of Australian tea tree oil, confirmed by positive wheal and flare reaction on skin testing.

  17. Talent in autism: hyper-systemizing, hyper-attention to detail and sensory hypersensitivity.

    PubMed

    Baron-Cohen, Simon; Ashwin, Emma; Ashwin, Chris; Tavassoli, Teresa; Chakrabarti, Bhismadev

    2009-05-27

    We argue that hyper-systemizing predisposes individuals to show talent, and review evidence that hyper-systemizing is part of the cognitive style of people with autism spectrum conditions (ASC). We then clarify the hyper-systemizing theory, contrasting it to the weak central coherence (WCC) and executive dysfunction (ED) theories. The ED theory has difficulty explaining the existence of talent in ASC. While both hyper-systemizing and WCC theories postulate excellent attention to detail, by itself excellent attention to detail will not produce talent. By contrast, the hyper-systemizing theory argues that the excellent attention to detail is directed towards detecting 'if p, then q' rules (or [input-operation-output] reasoning). Such law-based pattern recognition systems can produce talent in systemizable domains. Finally, we argue that the excellent attention to detail in ASC is itself a consequence of sensory hypersensitivity. We review an experiment from our laboratory demonstrating sensory hypersensitivity detection thresholds in vision. We conclude that the origins of the association between autism and talent begin at the sensory level, include excellent attention to detail and end with hyper-systemizing.

  18. PERSISTENT SUPPRESSION OF CONTACT HYPERSENSITIVITY, AND ALTERED T-CELL PARAMETERS IN F344 RATS EXPOSED PERINATALLY TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)

    EPA Science Inventory

    Abstract
    The outcome of perinatal low-level TCDD exposure on the T cell-mediated contact hypersensitivity response (CHS) in adult F344 rats was investigated. Suppression of the 2,4- dinitrofluorobenzene (DNFB)-specific contact hypersensitivity reponse occurred in mature off...

  19. [Administration of premedication with fexofenadine for paclitaxel-induced hypersensitive reactions in breast cancer patients complicated with closed-angle glaucoma].

    PubMed

    Komatsubara, Kazuo; Miyoshi, Kyoko; Kogure, Yuuki; Matsuhisa, Tetsuaki; Eguchi, Hisae

    2010-01-01

    Paclitaxel (PTX) is one of the most important breast cancer treatment drugs. However, severe hypersensitivity reactions such as decreases in blood pressure and impaired breathing occur with high frequency. For the prevention of such hypersensitivity reactions, administration of a premedication composed of three components, diphenhydramine, ranitidine (or famotidine), and dexamethasone, has been advised in package insert information of medicine. Administration of diphenhydramine is difficult in breast cancer patients complicated with closed-angle glaucoma, because diphenhydramine has a weak anticholinergic adverse effect which can induce mydriasis and glaucoma attack. We studied the prevention of severe hypersensitivity reactions and of glaucoma attack in 2 breast cancer patients complicated with closed angle glaucoma at our hospital from April 2007 to March 2008. We switched from diphenhydramine to fexofenadine as the medicine to prevent hypersensitivity reactions. Hypersensitivity reactions were not observed throughout all courses in both patients, and no glaucoma attack was observed.

  20. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    SciTech Connect

    Tamura, Akitoshi Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  1. STUDIES ON THE TUBERCULIN REACTION AND ON SPECIFIC HYPERSENSITIVENESS IN BACTERIAL INFECTION.

    PubMed

    Zinsser, H

    1921-10-31

    The work reported in the preceding sections justifies, we think, a number of definite conclusions. In addition to this, some of the experiments indicate a line of thought which may lead to considerable alteration in our conceptions, both of phenomena of bacterial hypersensitiveness and of infection. 1. In guinea pigs two fundamentally different types of intradermal reactions may be observed. One of these is the immediate, transitory reaction which develops in animals sensitized against proteins (horse serum, etc.) and may be regarded as one of the manifestations of general protein hypersensitiveness, or anaphylaxis; the other is the tuberculin type of skin reaction which develops more slowly, leads to a more profound injury of the tissues and is independent of anaphylaxis as ordinarily conceived. 2. The tuberculin type of hypersensitiveness (as well as probably the typhoidin, mallein, abortin reactions, etc.) does not develop at all in guinea pigs sensitized with proteins, like horse serum, etc. While this form of hypersensitiveness may eventually be induced with materials not bacterial in origin, it has been observed up to date only as a reaction of bacterial infection. 3. Methods of treatment with protein material from bacterial cultures which sensitize guinea pigs to anaphylactic reactions with the bacterial extracts, do not sensitize them to the tuberculin type of reaction. Such sensitization is easily accomplished only by infecting the animals with living organisms. No reliable method of sensitizing guinea pigs to such reactions with dead bacterial material has as yet been worked out, though a few hopeful experiments have been obtained with massive injections of large amounts of the acid-precipitable substances (nucleoproteins?) from bacterial extracts. 4. In animals made hypersensitive to the tuberculin type of reaction by infection with living bacteria, the reaction may be elicited by intradermal injections of bacterial extracts from which all coagulable

  2. Clinical evaluation of low-power laser and a desensitizing agent on dentin hypersensitivity.

    PubMed

    Lopes, Anely Oliveira; Eduardo, Carlos de Paula; Aranha, Ana Cecília Correa

    2015-02-01

    The aim of this randomized, longitudinal clinical study was to evaluate different protocols for dentin hypersensitivity treatment with low-power laser at different dosages, desensitizing agent, and associations, for a period of 6 months. After analysis of the inclusion and exclusion criteria of volunteer participants, those who present pain resulting from non-carious cervical lesions were selected. Twenty-seven patients participated in the study, and 55 lesions were recorded. The lesions were divided into five groups (n = 11), treated, and evaluated: G1: Gluma Desensitizer (Heraeus); G2: low-power laser (Photon Lase, DMC) at low dose (three vestibular points and one apical point of irradiation: 30 mW, 10 J/cm(2), 9 s per point with wavelength of 810 nm), three sessions were performed with an interval of 72 h between them; G3: low-power laser at high dose (application at one cervical and one apical point: 100 mW, 90 J/cm(2), 11 s per point with wavelength of 810 nm), three sessions were performed with an interval of 72 h between irradiations; G4: low-power laser at low dose + Gluma Desensitizer; and G5: low-power laser at high dose + Gluma Desensitizer, the level of sensitivity of each volunteer was evaluated with a visual analog scale of pain (VAS) with the use of air from a triple syringe and exploration with a probe after time intervals of 5 min, 1 week, and 1, 3, and 6 months after treatment. Data were collected and subjected to statistical analysis. Kolmogorov-Smirnov test was used to verify the distribution of the data, and nonparametric Kruskal-Wallis and Friedman tests were performed for comparison among the experimental groups and time intervals studied, respectively. Statistically significant differences between the studied time intervals (p < 0.05) were detected. From the difference in pain, it was observed that for both stimuli, the protocol with the Gluma desensitizing agent presented immediate effects of pain reduction. For low

  3. Tunicate-Inspired Gallic Acid/Metal Ion Complex for Instant and Efficient Treatment of Dentin Hypersensitivity.

    PubMed

    Prajatelistia, Ekavianty; Ju, Sung-Won; Sanandiya, Naresh D; Jun, Sang Ho; Ahn, Jin-Soo; Hwang, Dong Soo

    2016-04-20

    Dentin hypersensitivity is sharp and unpleasant pains caused by exposed dentinal tubules when enamel outside of the tooth wears away. The occlusion of dentinal tubules via in situ remineralization of hydroxyapatite is the best method to alleviate the symptoms caused by dentin hypersensitivity. Commercially available dental desensitizers are generally effective only on a specific area and are relatively toxic, and their performance usually depends on the skill of the clinician. Here, a facile and efficient dentin hypersensitivity treatment with remarkable aesthetic improvement inspired by the tunicate-self-healing process is reported. As pyrogallol groups in tunicate proteins conjugate with metal ions to heal the torn body armor of a tunicate, the ingenious mechanism by introducing gallic acid (GA) as a cheap, abundant, and edible alternative to the pyrogallol groups of the tunicate combined with a varied daily intake of metal ion sources is mimicked. In particular, the GA/Fe(3+) complex exhibits the most promising results, to the instant ≈52% blockage in tubules within 4 min and ≈87% after 7 d of immersion in artificial saliva. Overall, the GA/metal ion complex-mediated coating is facile, instant, and effective, and is suggested as an aesthetic solution for treating dentin hypersensitivity.

  4. Use of prasugrel in the setting of clopidogrel hypersensitivity: Case report and systematic review of the literature.

    PubMed

    Siu, Henry; Kaliyadan, Antony; Fischman, David L; Nardone, Evan; Poll, David; Savage, Michael P

    2016-12-01

    Allergic reactions to clopidogrel soon after coronary stent implantation pose an important and challenging clinical problem. We describe a 44-year-old man who developed a diffuse maculopapular rash four days after initiation of clopidogrel with drug-eluting coronary stent placement. An initial treat-through strategy was unsuccessful due to patient intolerance to corticosteroids. Because of persistent hypersensitivity, clopidogrel was substituted with prasugrel which was continued successfully for one year without reaction. A systematic review of the literature was performed which identified 10 prior case reports of patients with clopidogrel hypersensitivity who were subsequently treated with prasugrel. Patient characteristics and clinical outcomes of these patients plus the current case were reviewed. There were 9 men and 2 women with ages from 44 to 76 years. All patients had undergone coronary stent procedures. Prasugrel was successfully used without cross-reactivity in 9 of the 11 patients (82%). Cross-reactivity was reported in two patients who developed hypersensitivity reactions to prasugrel similar to those experienced on clopidogrel. In conclusion, prasugrel can be used successfully in most patients with a history of clopidogrel hypersensitivity. However, potential cross-reactivity between these two thienopyridines may occur in some patients.

  5. A connected set of genes associated with programmed cell death implicated in controlling the hypersensitive response in maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rp1-D21 is a maize auto-active resistance gene that confers a spontaneous hypersensitive response (HR). Depending on the genetic background in which it operates; variable levels of HR are observed. This offers a convenient system to identify alleles that modulate HR and genes involved in disease res...

  6. Cytoplasmic and nuclear localizations are important for the hypersensitive response conferred by maize autoactive Rp1-D21 protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Disease resistance (R-) genes have been isolated from many plant species. Most encode nucleotide binding leucine-rich-repeat (NLR) proteins that trigger a rapid localized programmed cell death termed the hypersensitive response (HR) upon pathogen recognition. Despite their structural similarities, d...

  7. Rash and hepatitis within days of starting a new antiretroviral regimen: nevirapine hypersensitivity, secondary syphilis or both?

    PubMed

    Saxon, Cara J; Helbert, Matthew R; Komolafe, Adeniyi J; Higgins, Stephen P

    2014-03-01

    We report a case in which an HIV-positive man developed general malaise, skin rash and biochemical hepatitis within days of starting a nevirapine-based antiretroviral treatment regimen. At the same time, his syphilis serology proved positive. We discuss the diagnostic dilemma: was this a nevirapine hypersensitivity reaction, secondary syphilis or both?

  8. Variation in plant defense against invasive herbivores: evidence for a hypersensitive response in eastern hemlocks (Tsuga canadensis).

    PubMed

    Radville, Laura; Chaves, Arielle; Preisser, Evan L

    2011-06-01

    Herbivores can trigger a wide array of morphological and chemical changes in their host plants. Feeding by some insects induces a defensive hypersensitive response, a defense mechanism consisting of elevated H(2)O(2) levels and tissue death at the site of herbivore feeding. The invasive hemlock woolly adelgid Adelges tsugae ('HWA') and elongate hemlock scale Fiorinia externa ('EHS') feed on eastern hemlocks; although both are sessile sap feeders, HWA causes more damage than EHS. The rapid rate of tree death following HWA infestation has led to the suggestion that feeding induces a hypersensitive response in hemlock trees. We assessed the potential for an herbivore-induced hypersensitive response in eastern hemlocks by measuring H(2)O(2) levels in foliage from HWA-infested, EHS-infested, and uninfested trees. Needles with settled HWA or EHS had higher H(2)O(2) levels than control needles, suggesting a localized hypersensitive plant response. Needles with no direct contact to settled HWA also had high H(2)O(2) levels, suggesting that HWA infestation may induce a systemic defense response in eastern hemlocks. There was no similar systemic defensive response in the EHS treatment. Our results showed that two herbivores in the same feeding guild had dramatically different outcomes on the health of their shared host.

  9. Identification of a Maize Locus that Modulates the Hypersensitive Defense Response, Using Mutant-Assisted Gene Identification and Characterization (MAGIC)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The hypersensitive response (HR) is the most visible and arguably the most important defense response in plants, although the details of how it is controlled and executed remain patchy. In this paper a novel genetic technique called MAGIC (Mutant-Assisted Gene Identification and Characterization) i...

  10. TRPV1-mediated presynaptic transmission in basolateral amygdala contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation

    PubMed Central

    Xiao, Ying; Chen, Xiaoqi; Zhang, Ping-An; Xu, Qiya; Zheng, Hang; Xu, Guang-Yin

    2016-01-01

    The central mechanisms of visceral hypersensitivity remain largely unknown. It’s reported that there are highest densities of TRPV1 labeled neurons within basolateral amygdala (BLA). The aim of this study was to explore the role and mechanisms of TRPV1 in BLA in development of visceral hypersensitivity. Visceral hypersensitivity was induced by neonatal maternal deprivation (NMD) and was quantified by abdominal withdrawal reflex. Expression of TRPV1 was determined by Western blot. The synaptic transmission of neurons in BLA was recorded by patch clamping. It was found that the expression of TRPV1 in BLA was significantly upregulated in NMD rats; glutamatergic synaptic activities in BLA were increased in NMD rats; application of capsazepine (TRPV1 antagonist) decreased glutamatergic synaptic activities of BLA neurons in NMD slices through a presynaptic mechanism; application of capsaicin (TRPV1 agonist) increased glutamatergic synaptic activities of BLA neurons in control slices through presynaptic mechanism without affecting GABAergic synaptic activities; microinjecting capsazepine into BLA significantly increased colonic distension threshold both in control and NMD rats. Our data suggested that upregulation of TRPV1 in BLA contributes to visceral hypersensitivity of NMD rats through enhancing excitation of BLA, thus identifying a potential target for treatment of chronic visceral pain. PMID:27364923

  11. In vitro Models to Evaluate Drug-Induced Hypersensitivity: Potential Test Based on Activation of Dendritic Cells

    PubMed Central

    Galbiati, Valentina; Papale, Angela; Kummer, Elena; Corsini, Emanuela

    2016-01-01

    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. PMID:27462271

  12. Diagnoses and Management of Drug Hypersensitivity and Anaphylaxis in Cancer and Chronic Inflammatory Diseases: Reactions to Taxanes and Monoclonal Antibodies.

    PubMed

    Bonamichi-Santos, Rafael; Castells, Mariana

    2016-06-08

    Due to the increase in utilization of chemotherapies and antibodies, drug hypersensitivity reactions have increased dramatically worldwide, preventing the use of first-line therapies and impacting patients' survival and quality of life. Some of the more frequently used medications in cancer include taxanes for ovarian, lung, breast, and prostate cancers. Monoclonal antibodies are used in the treatment of neoplastic, autoimmune, and inflammatory diseases, and their clinical applications are becoming broader. Monoclonal antibody targets include CD20, HER-2, EGFR, IL-6 receptor, TNF-α, CD30, VEGF-A, IgE, and more, and examples of immune-mediated and inflammatory diseases that respond to monoclonal antibodies include rheumatoid arthritis, Crohn's disease, ulcerative colitis, juvenile idiopathic arthritis, psoriasis and psoriatic arthritis, Wegener's granulomatosis, microscopic polyangiitis, ankylosing spondylitis, plaque psoriasis, and asthma. Neoplastic diseases include non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and colorectal, breast, gastric, and lung cancer. The clinical presentation of drug hypersensitivity reactions ranges from mild cutaneous reactions to life-threatening symptoms including anaphylaxis. Rapid drug desensitization (RDD) has become a groundbreaking approach to the management of immediate drug hypersensitivity reactions IgE and non-IgE mediated. It is the only effective procedure that enables sensitized patients to receive the full treatment dose safely, thus representing an important advance in the patients' treatment and prognosis. The aim of this review is to provide an update on hypersensitivity reactions to commonly used monoclonal and taxanes, their clinical presentations, diagnosis, and the use of RDD for their management.

  13. Molecular cloning and characterization of two hypersensitive induced reaction genes from wheat infected by stripe rust pathogen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel gene induced during hypersensitive reaction (HIR) in wheat was identified using in silico cloning and designated as TaHIR2. The TaHIR2 gene was deduced to encode a 284-amino acid protein, whose molecular mass and isoelectric point (pI) were 31.05 kD and 5.18, respectively. Amino acid sequenc...

  14. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Neural and neuro-immune mechanisms of visceral hypersensitivity in irritable bowel syndrome.

    PubMed

    Feng, Bin; La, Jun Ho; Schwartz, Erica S; Gebhart, G F

    2012-05-15

    Irritable bowel syndrome (IBS) is characterized as functional because a pathobiological cause is not readily apparent. Considerable evidence, however, documents that sensitizing proinflammatory and lipotoxic lipids, mast cells and their products, tryptases, enteroendocrine cells, and mononuclear phagocytes and their receptors are increased in tissues of IBS patients with colorectal hypersensitivity. It is also clear from recordings in animals of the colorectal afferent innervation that afferents exhibit long-term changes in models of persistent colorectal hypersensitivity. Such changes in afferent excitability and responses to mechanical stimuli are consistent with relief of discomfort and pain in IBS patients, including relief of referred abdominal hypersensitivity, upon intra-rectal instillation of local anesthetic. In the aggregate, these experimental outcomes establish the importance of afferent drive in IBS, consistent with a larger literature with respect to other chronic conditions in which pain is a principal complaint (e.g., neuropathic pain, painful bladder syndrome, fibromyalgia). Accordingly, colorectal afferents and the environment in which these receptive endings reside constitute the focus of this review. That environment includes understudied and incompletely understood contributions from immune-competent cells resident in and recruited into the colorectum. We close this review by highlighting deficiencies in existing knowledge and identifying several areas for further investigation, resolution of which we anticipate would significantly advance our understanding of neural and neuro-immune contributions to IBS pain and hypersensitivity.

  15. A Systematic Desensitization Paradigm to Treat Hypersensitivity to Auditory Stimuli in Children with Autism in Family Contexts

    ERIC Educational Resources Information Center

    Koegel, Robert L.; Openden, Daniel; Koegel, Lynn Kern

    2004-01-01

    Many children with autism display reactions to auditory stimuli that seem as if the stimuli were painful or otherwise extremely aversive. This article describes, within the contexts of three experimental designs, how procedures of systematic desensitization can be used to treat hypersensitivity to auditory stimuli in three young children with…

  16. The wheat ABA hypersensitive ERA8 mutant is associated with increased preharvest sprouting tolerance and altered hormone accumulation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wheat preharvest sprouting (PHS) is the germination of mature grain on the mother plant when rain occurs before harvest. Higher abscisic acid (ABA) hormone levels and sensitivity are associated with higher seed dormancy and PHS tolerance. Consistent with this, the ABA hypersensitive ERA8 (Enhanced...

  17. A genome-wide association study of the maize hypersensitive defense response identifies genes that cluster in related pathways

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Much remains unknown of molecular events controling the plant hypersensitive response (HR), a rapid localized cell death that limits pathogen spread and is mediated by resistance (R-) genes. Natural modifiers of the ectopic HR phenotype induced by an aberrant auto-active R-gene (Rp1-D21), were mappe...

  18. TRPV1, but not TRPA1, in primary sensory neurons contributes to cutaneous incision-mediated hypersensitivity

    PubMed Central

    2013-01-01

    Background Mechanisms underlying postoperative pain remain poorly understood. In rodents, skin-only incisions induce mechanical and heat hypersensitivity similar to levels observed with skin plus deep incisions. Therefore, cutaneous injury might drive the majority of postoperative pain. TRPA1 and TRPV1 channels are known to mediate inflammatory and nerve injury pain, making them key targets for pain therapeutics. These channels are also expressed extensively in cutaneous nerve fibers. Therefore, we investigated whether TRPA1 and TRPV1 contribute to mechanical and heat hypersensitivity following skin-only surgical incision. Results Behavioral responses to mechanical and heat stimulation were compared between skin-incised and uninjured, sham control groups. Elevated mechanical responsiveness occurred 1 day post skin-incision regardless of genetic ablation or pharmacological inhibition of TRPA1. To determine whether functional changes in TRPA1 occur at the level of sensory neuron somata, we evaluated cytoplasmic calcium changes in sensory neurons isolated from ipsilateral lumbar 3–5 DRGs of skin-only incised and sham wild type (WT) mice during stimulation with the TRPA1 agonist cinnamaldehyde. There were no changes in the percentage of neurons responding to cinnamaldehyde or in their response amplitudes. Likewise, the subpopulation of DRG somata retrogradely labeled specifically from the incised region of the plantar hind paw showed no functional up-regulation of TRPA1 after skin-only incision. Next, we conducted behavior tests for heat sensitivity and found that heat hypersensitivity peaked at day 1 post skin-only incision. Skin incision-induced heat hypersensitivity was significantly decreased in TRPV1-deficient mice. In addition, we conducted calcium imaging with the TRPV1 agonist capsaicin. DRG neurons from WT mice exhibited sensitization to TRPV1 activation, as more neurons (66%) from skin-incised mice responded to capsaicin compared to controls (46%), and the

  19. Bivariate genomic analysis identifies a hidden locus associated with bacteria hypersensitive response in Arabidopsis thaliana

    PubMed Central

    Wang, Biao; Li, Zhuocheng; Xu, Weilin; Feng, Xiao; Wan, Qianhui; Zan, Yanjun; Sheng, Sitong; Shen, Xia

    2017-01-01

    Multi-phenotype analysis has drawn increasing attention to high-throughput genomic studies, whereas only a few applications have justified the use of multivariate techniques. We applied a recently developed multi-trait analysis method on a small set of bacteria hypersensitive response phenotypes and identified a single novel locus missed by conventional single-trait genome-wide association studies. The detected locus harbors a minor allele that elevates the risk of leaf collapse response to the injection of avrRpm1-modified Pseudomonas syringae (P = 1.66e-08). Candidate gene AT3G32930 with in the detected region and its co-expressed genes showed significantly reduced expression after P. syringae interference. Our results again emphasize that multi-trait analysis should not be neglected in association studies, as the power of specific multi-trait genotype-phenotype maps might only be tractable when jointly considering multiple phenotypes. PMID:28338080

  20. Cutaneous hypersensitivity tests in guinea-pig of lanolin and derivatives used in cosmetology.

    PubMed

    Bourrinet, P; Berkovic, A

    1981-06-01

    Summary Among the warnings which are now necessary in Europe for the protection of the consumer and which must appear on the packagings of cosmetic and corporal hygiene products, there is one concerning lanolin. The regulation requires the mention 'Important, this product contains lanolin'. Cutaneous allergic reactions have been reported in the last few years after application of products containing lanolin or lanolin derivatives although lanolin has been used for a long time. The paper describes tests of cutaneous hypersensitivity on the guinea-pig with lanolin, lanolin alcohol and a semi-liquid lanolin. No reaction was observed with a purified lanolin, even if it was old. A weak allergenic effect was shown with the semi-liquid derivative. Sensitization reactions were observed with a sample of lanolin fatty alcohols. These results were analysed and compared to those published in literature.

  1. Beyond immediate hypersensitivity: evolving roles for IgE antibodies in immune homeostasis and allergic diseases.

    PubMed

    Burton, Oliver T; Oettgen, Hans C

    2011-07-01

    Immunoglobulin E (IgE) antibodies have long been recognized as the antigen-specific triggers of allergic reactions. This review briefly introduces the established functions of IgE in immediate hypersensitivity and then focuses on emerging evidence from our own investigations as well as those of others that IgE plays important roles in protective immunity against parasites and exerts regulatory influences in the expression of its own receptors, FcεRI and CD23, as well as controlling mast cell homeostasis. We provide an overview of the multifaceted ways in which IgE antibodies contribute to the pathology of food allergy and speculate regarding potential mechanisms of action of IgE blockade.

  2. Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M.

    PubMed

    Singh, Thiyam Ramsing; Bakker, Sietske T; Agarwal, Sheba; Jansen, Michael; Grassman, Elke; Godthelp, Barbara C; Ali, Abdullah Mahmood; Du, Chang-hu; Rooimans, Martin A; Fan, Qiang; Wahengbam, Kebola; Steltenpool, Jurgen; Andreassen, Paul R; Williams, David A; Joenje, Hans; de Winter, Johan P; Meetei, Amom Ruhikanta

    2009-07-02

    FANCM is a component of the Fanconi anemia (FA) core complex and one FA patient (EUFA867) with biallelic mutations in FANCM has been described. Strikingly, we found that EUFA867 also carries biallelic mutations in FANCA. After correcting the FANCA defect in EUFA867 lymphoblasts, a "clean" FA-M cell line was generated. These cells were hypersensitive to mitomycin C, but unlike cells defective in other core complex members, FANCM(-/-) cells were proficient in monoubiquitinating FANCD2 and were sensitive to the topoisomerase inhibitor camptothecin, a feature shared only with the FA subtype D1 and N. In addition, FANCM(-/-) cells were sensitive to UV light. FANCM and a C-terminal deletion mutant rescued the cross-linker sensitivity of FANCM(-/-) cells, whereas a FANCM ATPase mutant did not. Because both mutants restored the formation of FANCD2 foci, we conclude that FANCM functions in an FA core complex-dependent and -independent manner.

  3. Hypersensitivity dermatitis following suction-assisted lipectomy: a complication of local anesthetic.

    PubMed

    Fine, P G; Dingman, D L

    1988-06-01

    We report a case of severe dermatitis involving the abdomen and thighs following suction-assisted lipectomy of these areas wherein local anesthetic containing the preservative methylparaben was used for infiltrative anesthesia. This use of local anesthetics with epinephrine can be of value in the performance of suction-assisted lipectomy to reduce blood loss, serve as an adjunct to other intraoperative anesthetic techniques, and for postoperative analgesia. Local anesthetic solutions commonly contain additives, which serve as antioxidants and antimicrobials. The most common of these preservatives is methylparaben, which can cause delayed hypersensitivity reactions. These reactions may be neither recognized nor clinically significant in small areas of infection, whereas in large body surface infiltrative procedures, such as suction-assisted lipectomy, these reactions may be of considerable consequence. This article reviews the pathophysiology and treatment of these reactions and gives recommendations for avoiding them.

  4. The basophil activation test: a sensitive test in the diagnosis of allergic immediate hypersensitivity to pristinamycin.

    PubMed

    Viel, Sébastien; Garnier, Lorna; Joly, Elodie; Rouzaire, Paul; Nosbaum, Audrey; Pralong, Pauline; Faudel, Amélie; Rioufol, Catherine; Bienvenu, Françoise; Bienvenu, Jacques; Berard, Frédéric

    2015-01-01

    Immediate hypersensitivity (IHS) reactions to macrolides and to macrolide-derived antibiotics like pristinamycin are uncommon. In this context, there is little data available to appreciate the true value of biological tools regarding the diagnosis of immediate allergy to pristinamycin. Here we assess the clinical usefulness of the basophil activation test (BAT) to differentiate allergic from nonallergic IHS to pristinamycin. Thirty-six patients were tested with skin tests as the gold standard and BAT. The BAT achieved a sensitivity of 76% and a specificity of 100%, implying an absence of false positive results. Multicenter studies remain to be performed to better define the sensitivity, specificity and interlaboratory variation of BAT in the diagnosis of allergy to pristinamycin and macrolides.

  5. [Summary of the Dutch College of General Practitioners' practice guideline on food hypersensitivity].

    PubMed

    Luning-Koster, Marleen N; Lucassen, Peter L B J; Boukes, Froukje S; Goudswaard, A N Lex

    2011-01-01

    October 2010 the Dutch College of General Practitioners issued a revised version of their previous practice guideline of 1995 on food hypersensitivity in infants. If patients suspect either themselves or their child of having a food allergy, this is usually not demonstrated in subsequent investigation. Wrongly prescribed elimination diets may have adverse effects. Examination of serum specific IgE levels has no place in the diagnosis of food allergy in general practice. An open elimination challenge is especially suitable in order to exclude a food allergy. A sure diagnosis of food allergy can only be made by a double-blind placebo-controlled food challenge. There are no proven effective measures that can prevent food allergy.

  6. Langerhans cell function dictates induction of contact hypersensitivity or unresponsiveness to DNFB in Syrian hamsters

    SciTech Connect

    Streilein, J.W.; Bergstresser, P.R.

    1981-09-01

    The relationship between distribution and function of Langerhans cells within the epidermis and the capacity of cutaneous surfaces to promote the induction of contact hypersensitivity to DNFB have been examined in inbred Syrian hamsters. In a manner very similar to previous findings in mice, the results indicate that hamster cutaneous surfaces deficient in normally functioning Langerhans cells, naturally (cheek pouch epithelium) or artificially (after perturbation with ultraviolet light), are inefficient at promoting DNFB sensitization. Instead, DNFB applied to these regions of skin results in the induction of a state of specific unresponsiveness. Viable lymphoid cells from unresponsive hamsters can transfer the unresponsiveness to naive hamsters suggesting that active suppression is at least partly responsible, probably mediated by T lymphocytes.

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

    SciTech Connect

    Dewair, M. )

    1989-01-01

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

  8. Fluctuating local moments, itinerant electrons, and the magnetocaloric effect: Compositional hypersensitivity of FeRh

    NASA Astrophysics Data System (ADS)

    Staunton, J. B.; Banerjee, R.; Dias, M. dos Santos; Deak, A.; Szunyogh, L.

    2014-02-01

    We describe an ab initio disordered local moment theory for materials with quenched static compositional disorder traversing first-order magnetic phase transitions. It accounts quantitatively for metamagnetic changes and the magnetocaloric effect. For perfect stoichiometric B2-ordered FeRh, we calculate the transition temperature of the ferromagnetic-antiferromagnetic transition to be Tt= 495 K and a maximum isothermal entropy change in 2 T of |ΔS|=21.1 J K-1 kg-1. A large (40%) component of |ΔS| is electronic. The transition results from a fine balance of competing electronic effects which is disturbed by small compositional changes; e.g., swapping just 2% Fe of "defects" onto the Rh sublattice makes Tt drop by 290 K. This hypersensitivity explains the narrow compositional range of the transition and impurity doping effects.

  9. Chronic Toxoplasmosis Modulates the Induction of Contact Hypersensitivity by TNCB in Mouse Model.

    PubMed

    Yang, Zhaoshou; Ahn, Hye-Jin; Nam, Ho-Woo

    2015-12-01

    Mouse models of chronic toxoplasmosis and atopic dermatitis (AD) were combined to clarify the effect of opportunistic Toxoplasma gondii infection on the development of AD. AD was induced as a chronic contact hypersensitivity (CHS) with repeated challenge of 2,4,6-trinitro-1-chlorobenzene (TNCB) on the dorsal skin of mice. TNCB induced skin thickness increases in both normal and toxoplasmic mice. The changing patterns were different from the sigmoidal which saturated at 20 days in normal mice to the convex saturated at 12 days in toxoplasmic mice with the crossing at 18 days. Compared to normal mice, toxoplasmic mice presented CHS more severely in earlier times and then moderately in later times. These data suggest that host immune modification by T. gondii infection enhances CHS in early times of atopic stimulation but soothes the reaction of CHS in later times in mouse model.

  10. Parkinson's disease and Alzheimer's disease: hypersensitivity to X rays in cultured cell lines.

    PubMed Central

    Robbins, J H; Otsuka, F; Tarone, R E; Polinsky, R J; Brumback, R A; Nee, L E

    1985-01-01

    Fibroblast and/or lymphoblastoid lines from patients with several inherited primary neuronal degenerations are hypersensitive to DNA-damaging agents. Therefore, lymphoblastoid lines were irradiated from patients with sporadic Parkinson's disease (PD), Alzheimer's disease, and amyotrophic lateral sclerosis. The mean survival values of the eight Parkinson's disease and of the six Alzheimer's disease lines, but not of the five amyotrophic lateral sclerosis lines, were less than that of the 28 normal lines. Our results with Parkinson's disease and Alzheimer's disease cells can be explained by a genetic defect arising as a somatic mutation during embryogenesis, causing defective repair of the X-ray type of DNA damage. Such a DNA repair defect could cause an abnormal accumulation of spontaneously occurring DNA damage in Parkinson's disease and Alzheimer's disease neurons in vivo, resulting in their premature death. PMID:3876409

  11. Hypersensitivity to mosquito bites as the primary clinical manifestation of an Epstein-Barr virus infection.

    PubMed

    Chiu, Tsu-Man; Lin, Yueh-Min; Wang, Shing-Chuang; Tsai, Yi-Giien

    2016-08-01

    Hypersensitivity to mosquito bites (HMB) is a rare disease characterized by intense local skin reactions with general symptoms, such as high fever and regional lymphadenopathy after mosquito bites. Epstein-Barr virus (EBV) chronic infection and NK cell lymphoproliferative disease have been reported first in diagnosed HMB patients. Here, we present the case of a 6-year-old girl with 2 months' history of bullae and necrotic skin lesions, accompanied by a high temperature, visual hallucinations, and liver dysfunction after mosquito bites. A histopathologic examination of the skin lesion showed vasculitis and EBV infection. We could not detect any findings of hematologic malignancies or NK cell proliferative disease in the patient. Clinicians should closely evaluate HMB patients for possible development of lymphoproliferative status or hematologic malignant disorders.

  12. Pharmacokinetics and effects of cetirizine in horses with insect bite hypersensitivity.

    PubMed

    Olsén, Lena; Bondesson, Ulf; Broström, Hans; Olsson, Ulf; Mazogi, Behnaz; Sundqvist, Marie; Tjälve, Hans; Ingvast-Larsson, Carina

    2011-03-01

    Horses with insect bite hypersensitivity (IBH) have difficulty in completely avoiding allergens, so effective treatment options are required. A randomised, placebo controlled and double blinded field study was conducted to determine the pharmacokinetics and efficacy in reducing dermatitis of the antihistamine cetirizine given orally at 0.4 mg/kg twice daily for 3 weeks. The influence of protection blankets and stabling were also investigated. The estimated maximum plasma concentration (C(max)) and trough plasma concentration of cetirizine were 135 ng/mL and 18 ng/mL, respectively. There was no difference in dermatitis reduction between the treatment and placebo groups (P = 0.77). The findings indicated that cetirizine was of no apparent benefit in treating IBH at the dose rate tested. The use of blankets and stabling were shown to have favourable influence on the dermatitis (P < 0.05) and may be the preferred options to prevent this condition.

  13. Drug-Induced Hypersensitivity Syndrome Caused by Carbamazepine Used for the Treatment of Trigeminal Neuralgia

    PubMed Central

    Ono, Yuko; Shirafuji, Yoshinori; Hamada, Toshihisa; Masui, Masanori; Obata, Kyoichi; Yao, Mayumi; Kishimoto, Koji; Sasaki, Akira

    2016-01-01

    An 88-year-old man was diagnosed with trigeminal neuralgia, and treatment of carbamazepine 200 mg/day was initiated. About 6 weeks later, the patient developed a skin rash accompanied by fever. He was admitted to hospital and diagnosed with drug-induced hypersensitivity syndrome (DIHS) caused by carbamazepine. Oral carbamazepine treatment was stopped, but blood tests showed acute liver and acute renal failure. Drug-induced lymphocyte stimulation test (DLST) for carbamazepine, human herpes virus-6 (HHV-6) IgG, and CMV-HRP were negative. Oral prednisolone therapy was begun 18 days later. The titer of HHV-6 IgG antibodies was then detected (640 times). Following treatment, liver and renal function improved and the erythema disappeared. PMID:27885344

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

    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.

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

    PubMed Central

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

    1982-01-01

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

  17. Ultraviolet-irradiated urocanic acid suppresses delayed-type hypersensitivity to herpes simplex virus in mice

    SciTech Connect

    Ross, J.A.; Howie, S.E.; Norval, M.; Maingay, J.; Simpson, T.J.

    1986-11-01

    Ultraviolet radiation is known to induce a transient defect in epidermal antigen presentation which leads to the generation of antigen-specific suppression of the delayed-type hypersensitivity (DTH) response. The putative receptor in skin for the primary event in UV-suppression is urocanic acid (UCA) which may then interact locally, or systemically, with antigen presenting cells or initiate a cascade of events resulting in suppression. We present the first direct evidence that UCA, when irradiated with a dose (96 mJ/cm2) of UVB radiation known to suppress the DTH response to herpes simplex virus, type 1 (HSV-1) in mice, can induce suppression following epidermal application or s.c. injection of the irradiated substance. This suppression is transferable with nylon wool-passed spleen cells.

  18. Azathioprine Hypersensitivity Syndrome: Two Cases of Febrile Neutrophilic Dermatosis Induced by Azathioprine

    PubMed Central

    Aleissa, Majed; Nicol, Perrine; Godeau, Marion; Tournier, Emilie; de Bellissen, Frederic; Robic, Marie-Angèle; Livideanu, Cristina Bulai; Mazereeuw-Hautier, Juliette; Paul, Carle

    2017-01-01

    Background Azathioprine is an immunosuppressive agent used in the treatment of immune-mediated diseases. Azathioprine hypersensitivity syndrome is a rare adverse reaction occurring a few days to weeks after the administration of azathioprine. Case 1 A 36-year-old male with ulcerative colitis presented with erythematous plaques, pustules and erosions on the lower back, buttocks and thighs associated with high fever (39°C) 2 weeks after the initiation of azathioprine 100 mg/day. Additional findings included leukocytosis (18.6 g/L) with neutrophilia (11.1 g/L) and elevated C-reactive protein (128 mg/L). Histopathology showed a dense infiltrate of neutrophils in the hair follicles. We increased the dose of prednisone to 1 mg/kg/day (60 mg/day) and azathioprine was discontinued. He had marked improvement within 3 weeks and did not have any relapse with a 1-year follow-up. Case 2 A 57-year-old male with ulcerative colitis presented with erythematous plaques and pustules on the lower limbs associated with high fever (40°C) 1 week after the initiation of azathioprine 75 mg/day. Leukocytosis with neutrophilia (13.6 g/L) and elevated C-reactive protein (344 mg/L) were among the laboratory findings. Histopathology showed a dense infiltrate of neutrophils in the hair follicles. The dose of prednisone was increased to 20 mg/day and azathioprine was discontinued, which led to complete remission within 7 days. He did not have any relapse with a 6-month follow-up. Conclusion The development of acute neutrophilic dermatitis 2 weeks after the initiation of azathioprine and the complete resolution after its withdrawal were in favor of azathioprine hypersensitivity syndrome. It should not be confused with Sweet syndrome associated with inflammatory bowel disease, as maintenance of azathioprine treatment may lead to life-threatening reactions. PMID:28203157

  19. Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity.

    PubMed

    Nazimek, Katarzyna; Bryniarski, Krzysztof; Askenase, Philip W

    2016-01-01

    Extracellular vesicles, such as exosomes, are newly recognized intercellular conveyors of functional molecular mechanisms. Notably, they transfer RNAs and proteins between different cells that can then participate in the complex pathogenesis of allergic and related hypersensitivity responses and disease mechanisms, as described herein. This review highlights this important new appreciation of the in vivo participation of such extracellular vesicles in the interactions between allergy-mediating cells. We take into account paracrine epigenetic exchanges mediated by surrounding stromal cells and the endocrine receipt of exosomes from distant cells via the circulation. Exosomes are natural ancient nanoparticles of life. They are made by all cells and in some form by all species down to fungi and bacteria, and are present in all fluids. Besides a new focus on their role in the transmission of genetic regulation, exosome transfer of allergens was recently shown to induce allergic inflammation. Importantly, regulatory and tolerogenic exosomes can potently inhibit allergy and hypersensitivity responses, usually acting nonspecifically, but can also proceed in an antigen-specific manner due to the coating of the exosome surface with antibodies. Deep analysis of processes mediated by exosomes should result in the development of early diagnostic biomarkers, as well as allergen-specific, preventive and therapeutic strategies. These will likely significantly diminish the risks of current allergen-specific parenteral desensitization procedures, and of the use of systemic immunosuppressive drugs. Since extracellular vesicles are physiological, they can be fashioned for the specific delivery of therapeutic molecular instructions through easily tolerated, noninvasive routes, such as oral ingestion, nasal administration, and perhaps even inhalation.

  20. The Effect of Calcium Sodium Phosphosilicate on Dentin Hypersensitivity: A Systematic Review and Meta-Analysis

    PubMed Central

    Chen, Bin; Mei, Li; Yao, Liang; Tian, Jinhui; Li, Huang

    2015-01-01

    Objective To investigate the effect of calcium sodium phosphosilicate (CSPS) in treating dentin hypersensitivity (DH) and to compare this effect to that of a negative (placebo) control. Materials and Methods Several databases, including Medline, EMBASE, Web of Science, The Cochrane Library, and the Chinese Biomedical Literature Database, were searched to identify relevant articles published through January 2015; grey literature (i.e., academic literature that is not formally published) was also searched. Two authors performed data extraction independently and jointly using data collection forms. The primary outcome was the DH pain response to routine activities or to thermal, tactile, evaporative, or electrical stimuli, and the secondary outcome was the side effects of CSPS use. Each study was evaluated using the Cochrane Collaboration tool for assessing risk bias. Meta-analysis of studies with the same participant demographics, interventions, controls, assessment methods and follow-up periods was performed. The Grading of Recommendations Assessment Development and Evaluation System was used to assess the quality of the evidence and the risk of bias across studies. Results Meta-analysis demonstrated that toothpaste containing 5% CSPS was more effective than the negative control at relieving dentin sensitivity, with the level of evidence classified as “moderate”. In addition, prophylaxis paste containing 15% calcium sodium phosphosilicate was favored over the negative control at reducing post-periodontal therapy hypersensitivity, with the level of evidence categorized as “low”. Only two studies reported side effects of CSPS use. Conclusions The majority of studies found that calcium sodium phosphosilicate was more effective than the negative control at alleviating DH. Because strong evidence is scarce, high-quality, well-designed clinical trials are required in the future before definitive recommendations can be made. PMID:26544035

  1. Evaluation of the irritancy and hypersensitivity potential following topical application of didecyldimethylammonium chloride

    PubMed Central

    Anderson, Stacey E.; Shane, Hillary; Long, Carrie; Lukomska, Ewa; Meade, B. Jean; Marshall, Nikki B.

    2016-01-01

    Didecyldimethylammonium chloride (DDAC) is a dialkyl-quaternary ammonium compound that is used in numerous products for its bactericidal, virucidal and fungicidal properties. There have been clinical reports of immediate and delayed hypersensitivity reactions in exposed individuals; however, the sensitization potential of DDAC has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAC following dermal exposure in a murine model. DDAC induced significant irritancy (0.5 and 1%), evaluated by ear swelling in female Balb/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625–1%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.17%. Dermal exposure to DDAC did not induce increased production of IgE as evaluated by phenotypic analysis of draining lymph node B-cells (IgE+B220+) and measurement of total serum IgE levels. Additional phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4+ T-cells, CD8+ T-cells and dendritic cells in the draining lymph nodes, along with significant increases in the percentage of B-cells (0.25% and 1% DDAC) at Day 10 following 4 days of dermal exposure. There was also a significant and dose-responsive increase in the number of activated CD44 + CD4 + and CD8+ T-cells and CD86+ B-cells and dendritic cells following exposure to all concentrations of DDAC. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAC following dermal exposure and raise concerns about the use of this chemical and other quaternary ammonium compounds that may elicit similar effects. PMID:27216637

  2. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2009.

    PubMed

    Sicherer, Scott H; Leung, Donald Y M

    2010-01-01

    This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insects, as well as advances in allergic skin disease that were reported in the Journal in 2009. Among key epidemiologic observations, several westernized countries report that more than 1% of children have peanut allergy, and there is some evidence that environmental exposure to peanut is a risk factor. The role of regulatory T cells, complement, platelet-activating factor, and effector cells in the development and expression of food allergy were explored in several murine models and human studies. Delayed anaphylaxis to mammalian meats appears to be related to IgE binding to the carbohydrate moiety galactose-alpha-1,3-galactose, which also has implications for hypersensitivity to murine mAb therapeutics containing this oligosaccharide. Oral immunotherapy studies continue to show promise for the treatment of food allergy, but determining whether the treatment causes tolerance (cure) or temporary desensitization remains to be explored. Increased baseline serum tryptase levels might inform the risk of venom anaphylaxis and might indicate a risk for mast cell disorders in persons who have experienced such episodes. Reduced structural and immune barrier function contribute to local and systemic allergen sensitization in patients with atopic dermatitis, as well as increased propensity of skin infections in these patients. The use of increased doses of nonsedating antihistamines and potential usefulness of omalizumab for chronic urticaria was highlighted. These exciting advances reported in the Journal can improve patient care today and provide insights on how we can improve the diagnosis and treatment of these allergic diseases in the future.

  3. Cost-effectiveness of various methods of diagnosing hypersensitivity to Alternaria.

    PubMed

    Escudero, A I; Sánchez-Guerrero, I M; Mora, A M; Soriano, V; López, J D; García, F J; Negro, J M; Hernández, J; Pagán, J A

    1993-01-01

    This study was undertaken for two reasons: 1) It is more difficult to diagnose hypersensitivity to molds than to other allergens, so an evaluation of diagnostic tests was needed. 2) Alternaria is the principal cause of mold sensitization in our area. Sixty-six patients (20 +/- 4 years) were selected and divided into two groups. Group A was made up of patients with rhinitis and/or asthma due to Alternaria sensitization. Group B consisted of patients sensitized to other allergens and patients with nonrespiratory allergic disorders. Skin tests (prick and intradermal), challenge tests (conjunctival, nasal, and bronchial), and specific IgE determination were performed for all patients. A biologically standardized extract of Alternaria tenuis (Alergia e Inmunología Abelló, S. A., Madrid, Spain) obtained from a single batch was used for all tests. Our diagnostic criterion was a clinical history of rhinitis or asthma that coincided with the results of nasal/bronchial challenge. The diagnostic value of the other tests was compared to this criterion. In the group of rhinitic patients, skin tests and conjunctival challenge were more sensitive than specific IgE determination. In asthmatic patients, the most sensitive techniques were nasal and conjunctival challenges, followed by prick and intradermal skin tests, and, lastly, serum specific IgE determination. When rhinitis and asthma were considered jointly, the most sensitive test was conjunctival challenge, followed by skin-prick and intradermal tests. All tests had the same specificity, regardless of disorder. Nasal challenge was positive in all patients. Skin tests are easy to perform, cheap, non-traumatic for the patient, and sufficiently specific and sensitive for the diagnosis of Alternaria hypersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Role of CCL7 in Type I Hypersensitivity Reactions in Murine Experimental Allergic Conjunctivitis

    PubMed Central

    Kuo, Chuan-Hui; Collins, Andrea M.; Boettner, Douglas R.; Yang, YanFen

    2017-01-01

    Molecules that are necessary for ocular hypersensitivity reactions include the receptors CCR1 and CCR3; CCL7 is a ligand for these receptors. Therefore, we explored the role of CCL7 in mast cell activity and motility in vitro and investigated the requirement for CCL7 in a murine model of IgE-mediated allergic conjunctivitis. For mast cells treated with IgE and Ag, the presence of CCL7 synergistically enhanced degranulation and calcium influx. CCL7 also induced chemotaxis in mast cells. CCL7-deficient bone marrow–derived mast cells showed decreased degranulation following IgE and Ag treatment compared with wild-type bone marrow–derived mast cells, but there was no difference in degranulation when cells were activated via an IgE-independent pathway. In vivo, CCL7 was upregulated in conjunctival tissue during an OVA-induced allergic response. Notably, the early-phase clinical symptoms in the conjunctiva after OVA challenge were significantly higher in OVA-sensitized wild-type mice than in control challenged wild-type mice; the increase was suppressed in CCL7-deficient mice. In the OVA-induced allergic response, the numbers of conjunctival mast cells were lower in CCL7-deficient mice than in wild-type mice. Our results demonstrate that CCL7 is required for maximal OVA-induced ocular anaphylaxis, mast cell recruitment in vivo, and maximal FcεRI-mediated mast cell activation in vitro. A better understanding of the role of CCL7 in mediating ocular hypersensitivity reactions will provide insights into mast cell function and novel treatments for allergic ocular diseases. PMID:27956527

  5. Basophil Reactivity as Biomarker in Immediate Drug Hypersensitivity Reactions—Potential and Limitations

    PubMed Central

    Steiner, Markus; Harrer, Andrea; Himly, Martin

    2016-01-01

    Immediate drug hypersensitivity reactions (DHRs) resemble typical immunoglobulin E (IgE)-mediated symptoms. Clinical manifestations range from local skin reactions, gastrointestinal and/or respiratory symptoms to severe systemic involvement with potential fatal outcome. Depending on the substance group of the eliciting drug the correct diagnosis is a major challenge. Skin testing and in vitro diagnostics are often unreliable and not reproducible. The involvement of drug-specific IgE is questionable in many cases. The culprit substance (parent drug or metabolite) and potential cross-reacting compounds are difficult to identify, patient history and drug provocation testing often remain the only means for diagnosis. Hence, several groups proposed basophil activation test (BAT) for the diagnosis of immediate DHRs as basophils are well-known effector cells in allergic reactions. However, the usefulness of BAT in immediate DHRs is highly variable and dependent on the drug itself plus its capacity to spontaneously conjugate to serum proteins. Stimulation with pure solutions of the parent drug or metabolites thereof vs. drug-protein conjugates may influence sensitivity and specificity of the test. We thus, reviewed the available literature about the use of BAT for diagnosing immediate DHRs against drug classes such as antibiotics, radio contrast media, neuromuscular blocking agents, non-steroidal anti-inflammatory drugs, and biologicals. Influencing factors like the selection of stimulants or of the identification and activation markers, the stimulation protocol, gating strategies, and cut-off definition are addressed in this overview on BAT performance. The overall aim is to evaluate the suitability of BAT as biomarker for the diagnosis of immediate drug-induced hypersensitivity reactions. PMID:27378928

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Black, L.; Pay, T. W.

    1975-01-01

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

  8. Transcriptomic Analysis of Prunus domestica Undergoing Hypersensitive Response to Plum Pox Virus Infection

    PubMed Central

    Rodamilans, Bernardo; San León, David; Mühlberger, Louisa; Candresse, Thierry; Neumüller, Michael; Oliveros, Juan Carlos; García, Juan Antonio

    2014-01-01

    Plum pox virus (PPV) infects Prunus trees around the globe, posing serious fruit production problems and causing severe economic losses. One variety of Prunus domestica, named ‘Jojo’, develops a hypersensitive response to viral infection. Here we compared infected and non-infected samples using next-generation RNA sequencing to characterize the genetic complexity of the viral population in infected samples and to identify genes involved in development of the resistance response. Analysis of viral reads from the infected samples allowed reconstruction of a PPV-D consensus sequence. De novo reconstruction showed a second viral isolate of the PPV-Rec strain. RNA-seq analysis of PPV-infected ‘Jojo’ trees identified 2,234 and 786 unigenes that were significantly up- or downregulated, respectively (false discovery rate; FDR≤0.01). Expression of genes associated with defense was generally enhanced, while expression of those related to photosynthesis was repressed. Of the total of 3,020 differentially expressed unigenes, 154 were characterized as potential resistance genes, 10 of which were included in the NBS-LRR type. Given their possible role in plant defense, we selected 75 additional unigenes as candidates for further study. The combination of next-generation sequencing and a Prunus variety that develops a hypersensitive response to PPV infection provided an opportunity to study the factors involved in this plant defense mechanism. Transcriptomic analysis presented an overview of the changes that occur during PPV infection as a whole, and identified candidates suitable for further functional characterization. PMID:24959894

  9. Analysis of Arabidopsis Accessions Hypersensitive to a Loss of Chloroplast Translation1[OPEN

    PubMed Central

    Parker, Nicole; Wang, Yixing; Meinke, David

    2016-01-01

    Natural accessions of Arabidopsis (Arabidopsis thaliana) differ in their ability to tolerate a loss of chloroplast translation. These differences can be attributed in part to variation in a duplicated nuclear gene (ACC2) that targets homomeric acetyl-coenzyme A carboxylase (ACCase) to plastids. This functional redundancy allows limited fatty acid biosynthesis to occur in the absence of heteromeric ACCase, which is encoded in part by the plastid genome. In the presence of functional ACC2, tolerant alleles of several nuclear genes, not yet identified, enhance the growth of seedlings and embryos disrupted in chloroplast translation. ACC2 knockout mutants, by contrast, are hypersensitive. Here we describe an expanded search for hypersensitive accessions of Arabidopsis, evaluate whether all of these accessions are defective in ACC2, and characterize genotype-to-phenotype relationships for homomeric ACCase variants identified among 855 accessions with sequenced genomes. Null alleles with ACC2 nonsense mutations, frameshift mutations, small deletions, genomic rearrangements, and defects in RNA splicing are included among the most sensitive accessions examined. By contrast, most missense mutations affecting highly conserved residues failed to eliminate ACC2 function. Several accessions were identified where sensitivity could not be attributed to a defect in either ACC2 or Tic20-IV, the chloroplast membrane channel required for ACC2 uptake. Overall, these results underscore the central role of ACC2 in mediating Arabidopsis response to a loss of chloroplast translation, highlight future applications of this system to analyzing chloroplast protein import, and provide valuable insights into the mutational landscape of an important metabolic enzyme that is highly conserved throughout eukaryotes. PMID:27707889

  10. The environmental hypersensitivity symptom inventory: metric properties and normative data from a population-based study

    PubMed Central

    2013-01-01

    Background High concomitant intolerance attributed to odorous/pungent chemicals, certain buildings, electromagnetic fields (EMF), and everyday sounds calls for a questionnaire instrument that can assess symptom prevalence in various environmental intolerances. The Environmental Hypersensitivity Symptom Inventory (EHSI) was therefore developed and metrically evaluated, and normative data were established. The EHSI consists of 34 symptom items, requires limited time to respond to, and provides a detailed and broad description of the individual’s symptomology. Methods Data from 3406 individuals who took part in the Västerbotten Environmental Health Study were used. The participants constitute a random sample of inhabitants in the county of Västerbotten in Sweden, aged 18 to 79 years, stratified for age and gender. Results Exploratory factor analysis identified five significant factors: airway symptoms (9 items; Kuder-Richardson Formula 20 coefficient, KR-20, of internal consistency = 0.74), skin and eye symptoms (6 items; KR-20 = 0.60), cardiac, dizziness and nausea symptoms (4 items; KR-20 = 0.55), head-related and gastrointestinal symptoms (5 items; KR-20 = 0.55), and cognitive and affective symptoms (10 items; KR-20 = 0.80). The KR-20 was 0.85 for the entire 34-item EHSI. Symptom prevalence rates in percentage for having the specific symptoms every week over the preceding three months constitute normative data. Conclusions The EHSI can be recommended for assessment of symptom prevalence in various types of environmental hypersensitivity, and with the advantage of comparing prevalence rates with normality. PMID:23837629

  11. Analysis of Arabidopsis Accessions Hypersensitive to a Loss of Chloroplast Translation.

    PubMed

    Parker, Nicole; Wang, Yixing; Meinke, David

    2016-11-01

    Natural accessions of Arabidopsis (Arabidopsis thaliana) differ in their ability to tolerate a loss of chloroplast translation. These differences can be attributed in part to variation in a duplicated nuclear gene (ACC2) that targets homomeric acetyl-coenzyme A carboxylase (ACCase) to plastids. This functional redundancy allows limited fatty acid biosynthesis to occur in the absence of heteromeric ACCase, which is encoded in part by the plastid genome. In the presence of functional ACC2, tolerant alleles of several nuclear genes, not yet identified, enhance the growth of seedlings and embryos disrupted in chloroplast translation. ACC2 knockout mutants, by contrast, are hypersensitive. Here we describe an expanded search for hypersensitive accessions of Arabidopsis, evaluate whether all of these accessions are defective in ACC2, and characterize genotype-to-phenotype relationships for homomeric ACCase variants identified among 855 accessions with sequenced genomes. Null alleles with ACC2 nonsense mutations, frameshift mutations, small deletions, genomic rearrangements, and defects in RNA splicing are included among the most sensitive accessions examined. By contrast, most missense mutations affecting highly conserved residues failed to eliminate ACC2 function. Several accessions were identified where sensitivity could not be attributed to a defect in either ACC2 or Tic20-IV, the chloroplast membrane channel required for ACC2 uptake. Overall, these results underscore the central role of ACC2 in mediating Arabidopsis response to a loss of chloroplast translation, highlight future applications of this system to analyzing chloroplast protein import, and provide valuable insights into the mutational landscape of an important metabolic enzyme that is highly conserved throughout eukaryotes.

  12. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Methods to assess visceral hypersensitivity in irritable bowel syndrome.

    PubMed

    Keszthelyi, D; Troost, F J; Masclee, A A

    2012-07-15

    Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, characterized by recurrent abdominal pain or discomfort in combination with disturbed bowel habits in the absence of identifiable organic cause. Visceral hypersensitivity has emerged as a key hypothesis in explaining the painful symptoms in IBS and has been proposed as a "biological hallmark" for the condition. Current techniques of assessing visceral perception include the computerized barostat using rectal distensions, registering responses induced by sensory stimuli including the flexor reflex and cerebral evoked potentials, as well as brain imaging modalities such as functional magnetic resonance imaging and positron emission tomography. These methods have provided further insight into alterations in pain processing in IBS, although the most optimal method and condition remain to be established. In an attempt to give an overview of these methods, a literature search in the electronic databases PubMed and MEDLINE was executed using the search terms "assessment of visceral pain/visceral nociception/visceral hypersensitivity" and "irritable bowel syndrome." Both original articles and review articles were considered for data extraction. This review aims to discuss currently used modalities in assessing visceral perception, along with advantages and limitations, and aims also to define future directions for methodological aspects in visceral pain research. Although novel paradigms such as brain imaging and neurophysiological recordings have been introduced in the study of visceral pain, confirmative studies are warranted to establish their robustness and clinical relevance. Therefore, subjective verbal reporting following rectal distension currently remains the best-validated technique in assessing visceral perception in IBS.

  13. Clinical efficiency of low-level diode laser in reducing dentin hypersensitivity

    NASA Astrophysics Data System (ADS)

    Clavijo, E. M. A.; Clavijo, V. R. G.; Bandéca, M. C.; Nadalin, M. R.; Andrade, M. F.; Saad, J. R. C.; Pelegrine, A. A.

    2009-10-01

    Dentin hipersensitivity (DH) is a relatively common clinical condition, especially in periodontal patients after treatment. In this study it was evaluated 28 teeth who presented dentin hypersensitivity. The teeth were subjected to clinical and radiographic exams and were divided into groups following the treatment and the time of examination after application proposed: GI: PO 3% (Potassium Oxalate—group control)/Baseline; GII: PO 3%/3 days after first session; GIII: PO 3%/6 days; GIV: PO 3%/30 days; GV: PO 3%/60 days; GVI: PO 3%/90 days; GVII: Laser (Low_level diode laser with 110 mW/cm2)/Baseline; GVIII: Laser/7 days after first session; GIX: Laser/14 days; GX: Laser/30 days; GXI: Laser/60 days; and GXII: Laser/90 days. The groups I-VI, the teeth were subjected to 3 applications (GI-GIII) of desensitizing agent at regular intervals of seven days. The Groups VII-XI, each tooth was subjected to three applications (GVII-GIX) in three different points (mesial, meddle and distal surfaces) with an interval of 72 h. The time of application in each point was of 33 s and the patients from both groups were followed up to 90 days. The nonparametric test Friedman (α = 0.05) was applied and the test of Mann Whitney (α = 0.05) was used to compare the time of examination between groups. The application of Laser was effective 6 days after first session and to PO was 30 days. It was observed that both treatments were effective for the reduction of dentin hypersensitivity, however the laser presented better effectiveness.

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

    PubMed

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

    1991-06-01

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

  15. Altered sympathovagal balance and pain hypersensitivity in TNBS-induced colitis

    PubMed Central

    Furgała, Agata; Dobrek, Łukasz; Juszczak, Kajetan; Thor, Piotr

    2016-01-01

    Introduction Pain hypersensitivity, abnormal motility and autonomic dysfunction contribute to functional symptoms of inflammatory bowel disease (IBD). Material and methods The aim of this study was to assess: nociceptive thresholds for mechanical allodynia (MA) and thermal hyperalgesia (TH), intestinal motility (distal colonic transit and emptying), and cardiac autonomic neuropathy (indices of heart rate variability – HRV) in male Wistar rats with experimental trinitrobenzene sulfonic acid (TNBS) induced colitis. To identify a potential vagal contribution the bilateral subdiaphragmatic vagotomy (SDV) was performed. Results Experimental colitis resulted in a significant decrease in pain threshold (MA 23.60 ±2.12, p < 0.001, TH 8.51 ±1.49, p < 0.001), reduced expulsion time (6.2 ±3.5, p < 0,01) and increase in the sympathetic autonomic activity (LFnu 32.54 ±21.16, p < 0.03). The animals with diminished vagal integrity presented with reduced gastrointestinal motility (39.8 ±25.1, p < 0.01) and a decrease in the parasympathetic high-frequency domain of HRV (HFnu 55.37 ±22.80, p < 0.002). The vagotomized rats with colitis showed the strongest nociceptive response (MA 22.46 ±3.02, p < 0.004; TH 7.99 ±1.12, p < 0.003) as well as significant changes in sympatho-vagal balance on HRV testing (LFnu 28.25 ±14.66, p < 0.04; HFnu 71.34 ±14.55, p < 0.04). Conclusions The relationship between the cardiovascular and gastrointestinal system is modulated by neural, hormonal and inflammatory factors. This leads to dysregulation of the brain-gut interactions in the course of IBD. Sensitization and visceral-somatic convergence trigger pain hypersensitivity and autonomic sympathovagal imbalance. While integral vagal innervation impacts analgesic mechanisms via modulation of the immune response, SDV raises sympathetic activity and induces excessive hyperalgesia. PMID:28144278