[A case of loxoprofen-induced pneumonitis pathologically resembling hypersensitivity pneumonitis].

PubMed

Tohyama, Masaki; Tamaki, Yuichiro; Toyama, Masato; Ishimine, Tomohiko; Miyazato, Akiko; Nakamoto, Atsushi; Miyara, Takayuki; Higa, Futoshi; Tateyama, Masao; Kawakami, Kazuyoshi; Nakamura, Hiroaki; Saito, Atsushi

2002-02-01

A 66-year-old woman was admitted to our hospital because of high fever, general fatigue, hypoxemia and liver dysfunction. Chest radiographs showed diffuse interstitial shadows in both lungs. We suspected drug-induced pneumonitis because of her history of drug administration for upper respiratory infection. Her symptoms and findings were markedly decreased by discontinuation of the drugs. Transbronchial lung biopsy specimens showed infiltration of eosinophils and lymphocytes to the alveolar septa, granuloma with Langhans' giant cells, and Masson bodies in a manner suggestive of hypersensitivity pneumonitis. Drug lymphocyte stimulation tests were negative except for loxoprofen. There was no recurrence of systemic or respiratory symptoms during overnight stays at home. On the basis of these findings, we arrived at a diagnosis of drug-induced pneumonitis caused by loxoprofen.

[Familial summer-type hypersensitivity pneumonitis in a husband and wife].

PubMed

Amemiya, Yuka; Shirai, Ryo; Ando, Syunji; Fujii, Hiroyuki; Iwata, Atsuko; Kai, Naoko; Otani, Satoshi; Umeki, Kenji; Ishii, Hiroshi; Kadota, Jun-Ichi

2008-11-01

We encountered a family in which two of four members, the husband and his wife, had summer-type hypersensitivity pneumonitis at the same time, about two months after they moved to the residence. A 45-year-old man had cough, fever and exertional dyspnea. Chest computed tomography showed diffuse centriloblar ground-glass attenuation in both lung fields. His 43-year-old wife had chest small nodular shadows and similar symptoms to his husband. Serum anti-Tricosporon cutaneum (T. asahi: serotype II and T. mucoides: serotype I) antibodies of both patients were at the positive level. They were given diagnosis as summer-type hypersensitivity pneumonitis by radiological, serological and histological examinations. The symptoms in both cases were improved immediately after administration of systemic corticosteroid. Summer-type hypersensitivity pneumonitis was assumed to be caused for about two months duration of expousure to antigen.

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. Copyright © 2011 Elsevier Inc. All rights reserved.

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

PubMed

Gupta, Amit; Rosenman, Kenneth D

2006-06-01

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

[Prolonged disease in a farmer with simultaneous Q fever pneumonia and subacute hypersensitivity pneumonitis].

PubMed

Nielsen, Monica Etler; Hilberg, Ole; Bendstrup, Elisabeth

2015-06-22

This case report describes the first incident of a patient with simultaneous occurrence of Q fever pneumonia and subacute hypersensitivity pneumonitis (HP). The 52-year-old patient was from his occupation as a farmer exposed to agents causing both diseases. Except for a weight loss in subacute/chronic incidents of HP the symptoms of Q fever and HP are similar. However, differences in CT findings and histopathology make it possible to differentiate between the two diseases. This report highlights the importance of a thorough occupational history.

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

Working with argan cake: a new etiology for hypersensitivity pneumonitis.

PubMed

Paris, Christophe; Herin, Fabrice; Reboux, Gabriel; Penven, Emmanuelle; Barrera, Coralie; Guidat, Cécile; Thaon, Isabelle

2015-03-06

Argan is now used worldwide in numerous cosmetic products. Nine workers from a cosmetic factory were examined in our occupational medicine department, following the diagnosis of a case of hypersensitivity pneumonitis (HP) related to handling of argan cakes. Operators were exposed to three forms of argan (crude granulates, powder or liquid) depending on the step of the process. All workers systematically completed standardized questionnaires on occupational and medical history, followed by medical investigations, comprising, in particular, physical examination and chest X-rays, total IgE and a systematic screening for specific serum antibodies directed against the usual microbial agents of domestic and farmer's HP and antigens derived from microbiological culture and extracts of various argan products. Subjects with episodes of flu-like syndrome several hours after handling argan cakes, were submitted to a one-hour challenge to argan cakes followed by physical examination, determination of Carbon Monoxide Diffusing Capacity (DLCO) and chest CT-scan on day 2, and, when necessary, bronchoalveolar lavage on day 4. Six of the nine workers experienced flu-like symptoms within 8 hours after argan handling. After challenge, two subjects presented a significant decrease of DLCO and alveolitis with mild lymphocytosis, and one presented ground glass opacities. These two patients and another patient presented significant arcs to both granulates and non-sterile powder. No reactivity was observed to sterile argan finished product, antigens derived from argan cultures (various species of Bacillus) and Streptomyces marokkonensis (reported in the literature to contaminate argan roots). We report the first evidence of hypersensitivity pneumonitis related to argan powder in two patients. This implies preventive measures to reduce their exposure and clinical survey to diagnose early symptoms. As exposure routes are different and antibodies were observed against argan powder and not

Metalworking fluid-associated hypersensitivity pneumonitis: a workshop summary.

PubMed

Kreiss, K; Cox-Ganser, J

1997-10-01

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

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

PubMed

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

2005-01-01

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

Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case-cohort study.

PubMed

Morell, Ferran; Villar, Ana; Montero, María-Ángeles; Muñoz, Xavier; Colby, Thomas V; Pipvath, Sudhakar; Cruz, María-Jesús; Raghu, Ganesh

2013-11-01

The clinical features of idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis can be indistinguishable; the need to eliminate occult environmental factors known to cause pulmonary fibrosis in patients suspected to have IPF during diagnostic evaluation is evident. We aimed to investigate occult, putative causes in the environments of patients diagnosed with IPF using tests beyond those conventionally used. In this case-cohort study, 60 consecutive patients diagnosed with IPF on the basis of the 2000 American Thoracic Society (ATS) and the European Respiratory Society (ERS) criteria were prospectively followed up every 4 months for 6 years between Jan 1, 2004, and Dec 31, 2009. At each visit a uniformly applied questionnaire was administered to these 60 patients to identify occult antigen exposure known to cause hypersensitivity pneumonitis. Patients underwent specific IgG determination, bronchoalveolar lavage, bronchial challenge testing with suspected antigens, and re-review of histopathological features in existing and subsequently obtained surgical lung biopsy samples and from lung explants. Specimens obtained from suspected sources from the patient's environment were subjected to cultures in microbiology laboratory. These clinical data and discussions among pulmonologists and radiologists familiar with IPF were used to confirm the diagnosis in accordance with 2011 ATS, ERS, Japanese Respiratory Society, and Latin American Thoracic Association guidelines; 46 of the 60 patients had IPF according to the 2011 guidelines, and our analyses in this study were focused on these 46 patients. 20 of the 46 (43%, 95% CI 29-58) patients with IPF according to 2011 guidelines had a subsequent diagnosis of chronic hypersensitivity pneumonitis: nine patients had positive bronchial challenge testing (eight of whom were also IgG positive and six of these patients also had surgical lung biopsy showing a pattern consistent with chronic hypersensitivity

Asthma, hypersensitivity pneumonitis and other respiratory diseases caused by metalworking fluids.

PubMed

Rosenman, Kenneth D

2009-04-01

To highlight advances in understanding the respiratory disease associated with metal machining, a common work process involving approximately 1.2 million workers in the USA. Recent studies emphasize that work-related asthma and hypersensitivity pneumonitis continue to be caused by exposure to metalworking fluid. Identification of an individual patient indicates the need for follow-up investigations at the work site to prevent additional disease and/or identify additional effected individuals. Identification of the causal agent for hypersensitivity pneumonitis has centered on microbial contamination of metalworking fluids with a number of studies focusing on Mycobacterium immunogenum. Both asthma and hypersensitivity pneumonitis occur among workers exposed to metalworking fluid. The incidence of these diseases among such workers is unknown. Outbreaks of these conditions continue to be identified among metal machinists. Whether these are true outbreaks associated with some breakdown in workplace controls or, rather the recognition of ongoing endemic disease that is typically misdiagnosed as pneumonia or common adult onset asthma, needs further evaluation. Further work to elucidate the specific causal agent(s) is necessary to affect effective workplace controls. Treating an identified individual case as an index case with a follow-up workplace investigation will only be possible if practicing physicians interact with public health authorities to report newly diagnosed cases.

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

PubMed

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

2013-10-04

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

Hypersensitivity pneumonitis: a complex lung disease.

PubMed

Riario Sforza, Gian Galeazzo; Marinou, Androula

2017-01-01

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

Methotrexate-induced Hypersensitivity Pneumonitis appearing after 30 years of use: a case report.

PubMed

Salehi, Mashal; Miller, Robertha; Khaing, Myint

2017-06-28

Methotrexate has been implicated in a variety of lung complications, one of which is hypersensitivity pneumonitis. Hypersensitivity pneumonitis most often occurs within the first year of starting low-dose orally administered methotrexate. We present a case of methotrexate-induced hypersensitivity pneumonitis after 30 years of methotrexate use, which is the first case to be reported so far. A 77-year-old African American woman with a history of rheumatoid arthritis presented with progressively worsening shortness of breath and nonproductive cough. She was on a daily dose of 2.5 mg of methotrexate that had been orally administered for the last 30 years. A physical examination was significant for fever of 38.2 °C (100.8 °F), tachycardia, bilateral basal crackles, and oxygen saturation of 88% on room air. A laboratory work up was significant for normal white blood cell count, increased eosinophil count of 18.3%, and erythrocyte sedimentation rate of 111 mm/hour. Sputum cultures were negative for any bacterial pathogens including acid-fast bacilli. Influenza and respiratory syncytial viral infection were ruled out. A (1-3)-B-D-glucan assay (Fungitell®) was within normal limits. Pulmonary embolism was ruled out and echocardiography was normal. A chest X-ray showed hazy opacity with prominent reticulation within the upper lung fields bilaterally, right greater than the left with no pleural effusion. Lung computed tomography revealed nonspecific bilateral upper lung opacification. A pulmonary function test was significant for no obstruction, normal maximum voluntary ventilation, and no restriction, with mildly decreased diffusion. Methotrexate was stopped, and our patient was started on prednisone 60 mg orally administered daily with dramatic clinical and radiologic improvement. Methotrexate-induced hypersensitivity pneumonitis usually occurs in the initial few weeks to months of starting treatment with methotrexate; however, it can occur late during therapy too

[Cutaneous lesions during hot-tub hypersensitivity pneumonitis: Pseudomonas folliculitis ?

PubMed

Sokolowsky, N; Rolland, L; Vandenhende, M-A; Colin, J-Y; Laurent, F; Morlat, P; Bonnet, F; Beylot-Barry, M

2017-04-01

Interstitial lung disease, cutaneous rash and elevated serum angiotensin converting enzyme (ACE) may suggest diagnoses other than sarcoidosis. A 58-year-old man had presented dyspnoea for 2 years with increased angiotensin-converting enzyme, as well as an interstitial syndrome and micronodules. The possibility of sarcoidosis was raised. Systemic corticosteroids resulted in improvement of the dyspnoea although it recurred on dose reduction. We noted fluctuating eczematous macules of the limbs with a histology of aspecific folliculitis. The identification of Mycobacterium avium complex (MAC) in the bronchoalveolar wash prompted us to initiate antimycobacterial therapy, but this was to no avail. Review of the CT-scan and questioning of the patient (daily use of a Jacuzzi for 7 years) resulted in diagnosis of hypersensitivity pneumonitis due to MAC. The cutaneous lesions were taken to indicate "hot tub folliculitis". Discontinuation of hot-tub use and a short course of oral corticosteroids resulted in healing within 4 months, with no recurrence at 2 years. HTL is a form of hypersensitivity pneumonitis due to the presence of MAC in the water of Jacuzzis. This condition regresses spontaneously without treatment on discontinuation of Jacuzzi use. Hot-tub folliculitis due to Pseudomonas aeruginosa (PA) presents as macules and papules on covered skin areas (swimsuit) within 48hours of bathing and often declines within 2 weeks. Our case is original as regards the concomitant lung and cutaneous involvement associated with Jacuzzi use, with an immunoallergic mechanism for the MAC and probably an infectious mechanism for the PA. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

PubMed Central

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

2017-01-01

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

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.

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

PubMed

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

2017-07-01

To estimate the reported incidence of occupational hypersensitivity pneumonitis (OHP) in the UK and to consider whether the pattern of attributed causation has changed over time. All cases of OHP reported to the SWORD scheme between January 1996 and December 2015 were classified into 1 of 10 categories of the suspected agent. Cases were grouped into four 5-year time periods to examine any changing pattern in incidence or suspected causation. For each time period, the annual incidence was calculated using the estimated number of reported cases and the working population of the UK. Between 1996 and 2015, there were 202 actual cases of OHP reported to SWORD, equating to an estimated 818 cases, when adjusting for the sampling ratio. Over this period, the annual UK incidence was 1.4 per million workers. The mean (SD) age of reported cases was 52 (13) years, and cases were four-times more likely to be men than women. Over the study period, there was a fall in the proportion of cases reported to be due to agricultural exposures (44-12%), and an increase in cases due to metalworking fluids (MWFs, 2-45%). Over the last 20 years, the incidence of OHP in the UK has been ∼1-2 cases per million workers per year. Working with water-based MWFs is now the most commonly suspected causative exposure for OHP cases reported to the SWORD scheme in the UK. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

PubMed

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

2010-02-01

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

Lung Transplantation for Hypersensitivity Pneumonitis

PubMed Central

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

2015-01-01

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

[Environmental causes of the distal airways disease. Hypersensitivity pneumonitis and rare causes].

PubMed

Dalphin, J-C; Didier, A

2013-10-01

Hypersensitivity pneumonitis is one of the most frequent causes of distal airways disease. It is associated with inflammation of the bronchioles, predominantly by lymphocytic infiltrates, and with granuloma formation causing bronchial obstruction. This inflammation explains the clinical manifestations and the airways obstruction seen on pulmonary function tests, most often in the distal airways but proximal in almost 20%. CT scan abnormalities reflect the lymphocytic infiltrates and air trapping and, in some cases, the presence of emphysema. Bronchiolitis induced by chronic inhalation of mineral particles or acute inhalation of toxic gases (such as NO2) are other examples of small airways damage due to environmental exposure. The pathophysiological mechanisms are different and bronchiolar damage is either exclusive or predominant. Bronchiolitis induced by tobacco smoke exposure, usually classified as interstitial pneumonitis, is easily diagnosed thanks to broncho-alveolar lavage. Its prognosis is linked to the other consequences of tobacco smoke exposure including respiratory insufficiency. Finally, the complex lung exposure observed in some rare cases (such as the World Trade Center fire or during wars) may lead to a less characteristic pattern of small airways disease. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Diagnosis of hypersensitivity pneumonitis by measurement of antibodies against environmental antigens

DOE Office of Scientific and Technical Information (OSTI.GOV)

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),more » was developed for measurement of antibodies against antigens relevant to Farmer's Lung Disease (FLD), a type of HP affecting farmers.« less

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

PubMed

Gómez Tejada, Ricardo A; Legarreta, Cora G; Enghelmayer, Juan Ignacio; Dianti, Milagros; Acuña, Silvana; Olmedo, Gloria

2017-01-01

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

Quantifying serum antibody in bird fanciers' hypersensitivity pneumonitis.

PubMed

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

2006-06-26

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. 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. 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. 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.

The hypersensitivity pneumonitis diagnostic index: use of non-invasive testing to diagnose hypersensitivity pneumonitis in metalworkers.

PubMed

Dangman, Kenneth H; Cole, Solon R; Hodgson, Michael J; Kuhn, Charles; Metersky, Mark L; Schenck, Paula; Storey, Eileen

2002-08-01

Since 1993, several outbreaks of hypersensitivity pneumonitis (HP) have been reported in metalworkers. We report the largest outbreak of HP in metalworkers yet known. It occurred in a Connecticut factory that produces precision parts for the aerospace industry. The workers typically presented with systemic and respiratory problems ("sick fatigue," myalgias, cough, dyspnea, wheezing, and chest tightness). They had variable findings on clinical tests, which complicated diagnosis. An HP diagnostic index was developed to help reduce the uncertainties in case identification. Data from 16 biopsy-confirmed cases and 14 non-HP patients were compared, and the HP diagnostic index was derived using variables that best discriminated between the two groups. The index is based on (a) work-related symptoms, (b) dry crackles on auscultation, (c) restrictive spirometry, (d) decreased diffusion capacity and/or increased A-a oxygen gradient, (e) elevated erythrocyte sedimentation rate, (f) abnormal radiographic images, and (g) abnormal gallium scans. We then applied the HP diagnostic index and, for comparison, the "Kenosha epidemiological case criteria" (developed during a recent HP outbreak in an automobile factory) to our data set. The HP diagnostic index and the Kenosha criteria confirmed HP in overlapping sets of 36 and 34 patients, respectively, that were both in good agreement with the clinical diagnoses. The HP diagnostic index relies less heavily on symptoms, subjective evaluations, and invasive tests than the Kenosha criteria, but both identified similar subsets of the 61 patients as having HP. The HP diagnostic index could provide a useful tool in future HP outbreaks, which are increasingly being recognized in metalworking facilities. Copyright 2002 Wiley-Liss, Inc.

[A case of flomoxef-induced pneumonitis].

PubMed

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

1992-04-01

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

Computed tomography in hypersensitivity pneumonitis: main findings, differential diagnosis and pitfalls.

PubMed

Dias, Olívia Meira; Baldi, Bruno Guedes; Pennati, Francesca; Aliverti, Andrea; Chate, Rodrigo Caruso; Sawamura, Márcio Valente Yamada; Carvalho, Carlos Roberto Ribeiro de; Albuquerque, André Luis Pereira de

2018-01-01

Hypersensitivity pneumonitis (HP) is a disease with variable clinical presentation in which inflammation in the lung parenchyma is caused by the inhalation of specific organic antigens or low molecular weight substances in genetically susceptible individuals. Alterations of the acute, subacute and chronic forms may eventually overlap, and the diagnosis based on temporality and presence of fibrosis (acute/inflammatory HP vs. chronic HP) seems to be more feasible and useful in clinical practice. Differential diagnosis of chronic HP with other interstitial fibrotic diseases is challenging due to the overlap of the clinical history, and the functional and imaging findings of these pathologies in the terminal stages. Areas covered: This article reviews the essential features of HP with emphasis on imaging features. Moreover, the main methodological limitations of high-resolution computed tomography (HRCT) interpretation are discussed, as well as new perspectives with volumetric quantitative CT analysis as a useful tool for retrieving detailed and accurate information from the lung parenchyma. Expert commentary: Mosaic attenuation is a prominent feature of this disease, but air trapping in chronic HP seems overestimated. Quantitative analysis has the potential to estimate the involvement of the pulmonary parenchyma more accurately and could correlate better with pulmonary function results.

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

PubMed Central

2014-01-01

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

Hypersensitivity pneumonitis in a hardwood processing plant related to heavy mold exposure.

PubMed

Veillette, Marc; Cormier, Yvon; Israël-Assayaq, Evelyne; Meriaux, Anne; Duchaine, Caroline

2006-06-01

Two workers employed in a hardwood floor plant presented symptoms suggestive of hypersensitivity pneumonitis (HP). At that plant, kiln-dried wood often shows moldy growth and is subsequently brought inside for processing. This study evaluated the environment in attempt to identify the causative antigen and verify whether other workers of this and similar plants had or were at risk of developing HP. Dust from dust-removing systems and molds on the surface of wood planks were collected and air samples taken from a sister plant. Blood samples, spirometry, and symptoms' questionnaires were obtained from 11 co-workers. Dense Paecilomyces growth was observed on the surface of the dried processed wood in the index plant. This fungal genus was not detected in the sister plant. An additional worker had symptoms suggestive of HP, and his bronchoalveolar lavage revealed a lymphocytic alveolitis. The 3 confirmed cases of HP and the other 10 workers had positive specific IgG antibodies to Paecilomyces. We report 3 cases of HP out of 13 workers and a 100% sensitization to molds in workers of a hardwood processing plant. This rate is much higher than what is commonly seen in other environments associated with HP. The drying process is suspected of being responsible for the massive Paecilomyces contamination likely responsible for the HP.

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

PubMed Central

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

2014-01-01

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

Polarized type 1 cytokine profile in bronchoalveolar lavage T cells of patients with hypersensitivity pneumonitis.

PubMed

Yamasaki, H; Ando, M; Brazer, W; Center, D M; Cruikshank, W W

1999-09-15

Hypersensitivity pneumonitis (HP) is characterized by an inflammatory lymphocytic alveolitis comprised of both CD8+ and CD4+ T cells. Animal models suggest that HP is facilitated by overproduction of IFN-gamma, and that IL-10 ameliorates severity of the disease, indicating a Th1-type response. To determine whether a Th1 phenotype in HP also exists clinically, bronchoalveolar lavage (BAL) and peripheral blood (PB) T cells were obtained from HP individuals and analyzed for Th1 vs Th2 cytokine profiles. It was determined that soluble OKT3-stimulated BAL T cells cocultured with alveolar macrophages produced more IFN-gamma and less IL-10 than PB T cells cocultured with monocytes, but no difference was observed in IL-4 production. The monocytic cells did not account for this difference, as CD80 and CD86 expressions were similar, and coculturing PB T cells with alveolar macrophages resulted in no difference in IFN-gamma production. Similarly, there was no difference in IL-12 production between stimulated BAL or PB T cells; however, addition of rIL-12 significantly increased production of IFN-gamma by BAL T cells, but not by PB T cells. This effect was due to a difference in IL-12R expression. High affinity IL-12R were only present in association with BAL T cells. These studies indicate that clinical HP is characterized by a predominance of IFN-gamma-producing T cells, perhaps resulting from a reduction in IL-10 production and an increase in high affinity IL-12R compared with blood T cells.

Chronic Hypersensitivity Pneumonitis With a Usual Interstitial Pneumonia-Like Pattern: Correlation Between Histopathologic and Clinical Findings.

PubMed

Chiba, Sahoko; Tsuchiya, Kimitake; Akashi, Takumi; Ishizuka, Masahiro; Okamoto, Tsukasa; Furusawa, Haruhiko; Tateishi, Tomoya; Kishino, Mitsuhiro; Miyazaki, Yasunari; Tateishi, Ukihide; Takemura, Tamiko; Inase, Naohiko

2016-06-01

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of environmental antigens. The relationship between clinical, radiologic, and histopathologic findings of chronic HP remains unclear. Sixteen patients with proven chronic bird-related HP with a usual interstitial pneumonia-like pattern were analyzed retrospectively. Histopathologic findings were semiquantitatively assessed and compared with clinical and radiologic findings. We also evaluated the histopathologic findings affecting prognosis. The extent of centrilobular fibrosis was negatively correlated with Pao2 (r = -0.55, P = .03). The extent of bridging fibrosis was positively correlated with the ratio of maximal expiratory flow at 50% of forced vital capacity to that at 25% (r = 0.60, P = .02). Patients with a greater extent of fibroblastic foci (FF) had more radiologic reticulation (P = .01), honeycombing (P = .01), and traction bronchiectasis (P = .02), and had significantly shorter survival time (P = .01) than patients with a lesser extent of FF. Multivariate analysis showed that the extent of FF was a significant prognostic factor (hazard ratio, 2.36; 95% confidence interval, 1.02-5.48; P = .04). Our findings demonstrated that the extent of FF was significantly associated with reticulation, honeycombing, and traction bronchiectasis on high-resolution CT scanning. Moreover, the extent of FF could be a useful predictor of mortality in chronic HP with a usual interstitial pneumonia-like pattern. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2013-12-01

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

Analysis of cellular and protein content of broncho-alveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

PubMed Central

Reynolds, H Y; Fulmer, J D; Kazmierowski, J A; Roberts, W C; Frank, M M; Crystal, R G

1977-01-01

To evaluate cellular and protein components in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP), limited broncho-alveolar lavage was done in 58 patients (19 IPF, 7 CHP, and 32 controls). Analysis of the cells and protein in the lavage fluids from patients with IPF revealed an inflammatory and eosinophilic response and a significant elevation of IgG in the lungs. With corticosteroid therapy, inflammation diminished but eosinophils remained. Lavage fluid from patients with CHP also had eosinophils and elevated levels of IgG. However, in contrast to IPF, lavage fluid from CHP patients contained IgM, fewer inflammatory cells, and a strikingly increased number (38-74%) of lymphocytes. Identification of lavage lymphocytes in CHP showed that T lymphocytes were significantly elevated and B lymphocytes were decreased compared to peripheral blood. These studies suggest nthat the lung in IPF and CHP may function as a relatively independent immune organ, and that analysis of cells and proteins in broncho-alveolar lavage fluid may be of diagnostic, therapeutic, and investigative value in evaluating patients with fibrotic lung disease. PMID:830661

A comparison of health-related quality of life in idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

PubMed

Lubin, Molly; Chen, Hubert; Elicker, Brett; Jones, Kirk D; Collard, Harold R; Lee, Joyce S

2014-06-01

Patients with interstitial lung disease (ILD) have poor health-related quality of life (HRQL). However, whether HRQL differs among different subtypes of ILD is unclear. The aim of this study was to determine whether HRQL was different among patients with idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP). We identified patients from an ongoing longitudinal cohort of patients with ILD. HRQL was assessed using the Short Form (SF)-36 medical outcomes form (version 2.0). Regression analysis was used to determine the association between clinical covariates and HRQL, primarily the physical component summary (PCS) and mental component summary (MCS) score. A multivariate regression model was created to identify potential covariates that could help explain the association between the ILD subtype and HRQL. Patients with IPF (n = 102) were older, more likely to be men, and more likely to have smoked. Pulmonary function was similar between the groups. The patients with CHP (n = 69) had worse HRQL across all eight domains of the SF-36, as well as the PCS and MCS, compared with patients with IPF (P < .01-.09). This pattern remained after controlling for age and pulmonary function (P < .01-.02). Covariates explaining part of the relationship between disease subtype and PCS score included severity of dyspnea (P < .01) and fatigue (P < .01). Covariates explaining part of the relationship between disease subtype and MCS score included severity of dyspnea (P < .01), female sex (P = .02), and fatigue (P = .02). HRQL is worse in CHP compared with IPF. HRQL differences between ILD subtypes are explained in part by differences in sex, dyspnea, and fatigue.

Hypersensitivity pneumonitis in a beautician.

PubMed

Soumagne, Thibaud; Reboux, Gabriel; Degano, Bruno; Dalphin, Jean Charles

2016-11-01

A 52-year-old non-smoking beautician using a skincare device spraying steam and ozone (a "vapozone" facial steamer) was referred for progressive dyspnea and dry cough during working periods. Although spirometry was normal, she had decreased diffusing capacity of the lung for carbon monoxide, bronchiolitis with air trapping on high-resolution CT scan and 60% lymphocytosis by bronchoalveolar lavage. Twenty-six antigens were tested and serum-specific precipitins were found mainly against Pseudomonas sp. and Mycobacterium mucogenicum. Cultures from her skincare device isolated Pseudomonas sp. Outcome was favorable with cessation of occupational exposure to the device, without any medication. This is the first report of a case of HP in a beautician due to steam contaminated by Pseudomonas sp. from a vapozone. HP, and not only asthma and contact dermatitis, should be suspected in beauticians with respiratory symptoms. Am. J. Ind. Med. 59:1041-1045, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

PubMed Central

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

2013-01-01

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

Effects of cigarette smoking on diagnostic tests for work-related hypersensitivity pneumonitis: data from an outbreak of lung disease in metalworkers.

PubMed

Dangman, Kenneth H; Storey, Eileen; Schenck, Paula; Hodgson, Michael J

2004-05-01

It is widely believed that development of hypersensitivity pneumonitis (HP) is forestalled in cigarette smokers. We encountered the largest outbreak of HP in metalworkers yet reported [Hodgson et al. (2001): Am J Ind Med 39:616-628] and subsequently did a chart review of the 61 patients seen in connection with the outbreak [Dangman et al. (2002a): Am J Resp Crit Care Med 165(8):A528; Dangman et al. (2002b): Am J Ind Med 42:150-162], developing a diagnostic index for this disease. A re-examination of data from the chart review was carried out to explore possible effects of cigarette smoking on the clinical tests used to diagnose HP [Hodgson et al. (2001): Am J Ind Med 39:616-628]. Cigarette smokers with HP were less likely than non-smokers with HP to develop crackles in the lungs, elevated erythrocyte sedimentation rates (ESRs), and restrictive spirometry. Smoking habits had little effect on diffusion capacity and alveolar-arterial oxygen gradients in the patients with HP. Smokers were more likely to have abnormal gallium scans than non-smokers. It appears that cigarette smoking can affect the physical examination findings, spirometry, and ESR changes associated with HP, making these tests less sensitive and specific, and potentially obscuring the diagnosis. Such changes may contribute to the apparent "protective" effect of smoking on the development of HP.

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

PubMed Central

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

2015-01-01

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

Human monocyte-derived dendritic cells exposed to microorganisms involved in hypersensitivity pneumonitis induce a Th1-polarized immune response.

PubMed

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

2013-08-01

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

Pneumonitis

MedlinePlus

... of lung inflammation. Common causes of pneumonitis include airborne irritants at your job or from your hobbies. ... alveoli into the bloodstream. Many irritants, ranging from airborne molds to chemotherapy drugs, have been linked to ...

Hypersensitivity Pneumonitis

MedlinePlus

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

How to Diagnose Early 5-Azacytidine-Induced Pneumonitis: A Case Report.

PubMed

Misra, Srimanta Chandra; Gabriel, Laurence; Nacoulma, Eric; Dine, Gérard; Guarino, Valentina

2017-12-01

Interstitial pneumonitis is a classical complication of many drugs. Pulmonary toxicity due to 5-azacytidine, a deoxyribonucleic acid methyltransferase inhibitor and cytotoxic drug, has rarely been reported. We report a 67-year-old female myelodysplastic syndrome patient treated with 5-azacytidine at the conventional dosage of 75 mg/m 2 for 7 days. One week after starting she developed moderate fever along with dry cough and subsequently her temperature rose to 39.5 °C. She was placed under broad-spectrum antibiotics based on the protocol for febrile neutropenia, including ciprofloxacin 750 mg twice daily, ceftazidime 1 g three times daily (tid), and sulfamethoxazole/trimethoprim 400 mg/80 mg tid. High-resolution computed tomography of the chest disclosed diffuse bilateral opacities with ground-glass shadowing and pleural effusion bilaterally. Mediastinal and hilar lymph nodes were moderately enlarged. polymerase chain reaction for Mycobacterium tuberculosis, Pneumocystis jiroveci, and cytomegalovirus were negative. Cultures including viral and fungal were all negative. A diagnosis of drug-induced pneumonitis was considered and, given the negative bronchoalveolar lavage in terms of an infection, corticosteroid therapy was given at a dose of 1 mg/kg body weight. Within 4 weeks, the patient became afebrile and was discharged from hospital. Development of symptoms with respect to drug administration, unexplained fever, negative workup for an infection, and marked response to corticosteroid therapy were found in our case. An explanation could be a delayed type of hypersensitivity (type IV) with activation of CD8 T cell which could possibly explain most of the symptoms. We have developed a decision algorithm in order to anticipate timely diagnosis of 5-azacitidine-induced pneumonitis, and with the aim to limit antibiotics abuse and to set up emergency treatment.

Chapter 17: Occupational immunologic lung disease.

PubMed

Sabin, Bradley R; Grammer, Leslie C

2012-01-01

Occupational immunologic lung disease is characterized by an immunologic response in the lung to an airborne agent inhaled in the work environment and can be subdivided into immunologically mediated occupational asthma (OA) and hypersensitivity pneumonitis (HP). Irritant-induced OA, a separate nonimmunologic entity, can be caused by chronic exposure to inhaled irritants or reactive airways dysfunction syndrome, defined as an asthma-like syndrome that persists for >3 months and occurs abruptly after a single exposure to a high concentration of an irritating industrial agent. High-risk fields for OA include farmers, printers, woodworkers, painters, plastic workers, cleaners, spray painters, electrical workers, and health care workers. OA can be triggered by high molecular weight (HMW) proteins that act as complete allergens or low molecular weight (LMW) sensitizers that act as haptens. HMW proteins (>10 kDa) are generally derived from microorganisms (such as molds and bacteria, including thermophilic actinomycetes), plants (such as latex antigens and flour proteins), or animals (such as animal dander, avian proteins, and insect scales) and are not specifically regulated by the Occupational Safety and Health Administration (OSHA). LMW haptens that bind to proteins in the respiratory mucosa include some OSHA-regulated substances such as isocyanates, anhydrides, and platinum. HP can present in an acute, a chronic, or a subacute form. The acute, subacute, and early chronic form is characterized by a CD4(+) T(H)1 and CD8(+) lymphocyte alveolitis. Classically, the bronchoalveolar lavage will show a CD4/CD8 ratio of <1.

Pneumonic Plague Cluster, Uganda, 2004

PubMed Central

Asiki, Gershim; Anywaine, Zaccheus; Yockey, Brook; Schriefer, Martin E.; Aleti, Philliam; Ogen-Odoi, Asaph; Staples, J. Erin; Sexton, Christopher; Bearden, Scott W.; Kool, Jacob L.

2006-01-01

The public and clinicians have long-held beliefs that pneumonic plague is highly contagious; inappropriate alarm and panic have occurred during outbreaks. We investigated communicability in a naturally occurring pneumonic plague cluster. We defined a probable pneumonic plague case as an acute-onset respiratory illness with bloody sputum during December 2004 in Kango Subcounty, Uganda. A definite case was a probable case with laboratory evidence of Yersinia pestis infection. The cluster (1 definite and 3 probable cases) consisted of 2 concurrent index patient–caregiver pairs. Direct fluorescent antibody microscopy and polymerase chain reaction testing on the only surviving patient's sputum verified plague infection. Both index patients transmitted pneumonic plague to only 1 caregiver each, despite 23 additional untreated close contacts (attack rate 8%). Person-to-person transmission was compatible with transmission by respiratory droplets, rather than aerosols, and only a few close contacts, all within droplet range, became ill. PMID:16704785

Proposed national strategies for the prevention of leading work-related diseases and injuries. Part 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1986-01-01

Preliminary strategies developed at the National Symposium on the Prevention of Leading Work Related Diseases and Injuries, held in Atlanta, Georgia on May 1 to 3, 1985 were revised, elaborated, and further developed. Strategies were developed for the prevention of occupational lung diseases, musculoskeletal injuries, occupational cancers, severe occupational traumatic injuries, and occupational cardiovascular diseases. Lung diseases considered included silicosis, asbestosis, lung cancer mesothelioma, coal workers' pneumoconiosis, byssinosis, occupational asthma, hypersensitivity pneumonitis, asphyxiation, irritation, pulmonary edema, brucellosis, psitticosis, anthrax, mycobacterioses, histoplasmosis, aspergillosis, and coccidioidomycosis. Occupational cancers were discussed as they occur in the lung, pleura, peritoneum, bladder, kidneys, blood, nasalmore » cavity, skin, nasal sinuses, and liver.« less

Pneumonic Plague: The Darker Side of Yersinia pestis.

PubMed

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

2016-03-01

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

Pneumonitis and pneumonia after aspiration

PubMed Central

Son, Young Gon; Shin, Jungho

2017-01-01

Aspiration pneumonitis and aspiration pneumonia are clinical syndromes caused by aspiration. These conditions are clinically significant due to their high morbidity and mortality. However, aspiration as a preceding event are often unwitnessed, particularly in cases of asymptomatic or silent aspiration. Furthermore, despite the difference in treatment approaches for managing aspiration pneumonitis and aspiration pneumonia, these two disease entities are often difficult to discriminate from one another, resulting in inappropriate treatment. The use of unclear terminologies hinders the comparability among different studies, making it difficult to produce evidence-based conclusions and practical guidelines. We reviewed the most recent studies to define aspiration, aspiration pneumonitis, and aspiration pneumonia, and to further assess these conditions in terms of incidence and epidemiology, pathophysiology, risk factors, diagnosis, management and treatment, and prevention. PMID:28879323

[Minocycline pneumonitis and eosinophilia].

PubMed

Fink, N; Mouallem, M

2000-06-15

Pneumonitis with eosinophilia is one of the less common and severe adverse effects of minocycline. The disease evolves in days or weeks from the beginning of treatment, and is usually characterized by dyspnea, fever and bilateral infiltrates in the chest X-ray. With cessation of the antibiotic, and sometimes adding cortico-steroids, clinical and roentgenological resolution follow. We present a case given minocycline for folliculitis and 3 weeks later fever, cough and shortness of breath developed. The clinical and roentgenological course was consistent with minocycline pneumonitis accompanied by eosinophilia.

Occupational lung disease survey of respiratory physicians in Northern Ireland.

PubMed

McKeagney, T F P; Addley, K; Asanati, K

2015-12-01

Respiratory physicians are likely to encounter occupational lung disease (OLD) in their daily practice. To assess the profile of cases being encountered by general respiratory physicians in Northern Ireland (NI) and determine satisfaction with training, confidence in diagnosis and management of OLD. An online survey of all consultant respiratory physicians currently practising in NI. Questions assessed the numbers of new cases seen over the preceding year, case type, satisfaction with specialist registrar training in OLD and degree of confidence in the diagnosis and management of these conditions. Of the 40 consultants identified, the response rate was 80% (n = 32) with 94% of respondents (n = 30) indicating they had dealt with patients suspected of having occupation-related respiratory symptoms. The most commonly encountered OLDs were pleural plaques (91% of respondents), occupational asthma (88%), asbestosis (84%), non-asbestosis pulmonary fibrosis (76%), hypersensitivity pneumonitis (67%) and mesothelioma (66%). Just over one third of consultants (36%, n = 10) indicated a lack of confidence in diagnosis and management of OLD with almost half (48%) dissatisfied with OLD training as a registrar and a further 78% (n = 25) indicating they would value additional training in OLD as a consultant. The majority of respiratory consultants in NI encountered OLD in their day to day practice and half were dissatisfied with their specialist registrar training in OLD and express a lack of confidence in the diagnosis and management of these conditions. This highlights the need for additional training at both registrar and consultant level. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Trichloroethylene Hypersensitivity Syndrome: A Disease of Fatal Outcome

PubMed Central

Jung, Hyun Gul; 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. PMID:22187259

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.

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

PubMed

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

2017-11-01

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

Vaccination against bubonic and pneumonic plague.

PubMed

Titball, R W; Williamson, E D

2001-07-20

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

Lung Size and the Risk of Radiation Pneumonitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Briere, Tina Marie, E-mail: tmbriere@mdanderson.org; Krafft, Shane; Liao, Zhongxing

2016-02-01

Purpose: The purpose of this study was to identify patient populations treated for non-small cell lung cancer (NSCLC) who may be more at risk of radiation pneumonitis. Methods and Materials: A total of 579 patients receiving fractionated 3D conformal or intensity modulated radiation therapy (IMRT) for NSCLC were included in the study. Statistical analysis was performed to search for cohorts of patients with higher incidences of radiation pneumonitis. In addition to conventional risk factors, total and spared lung volumes were analyzed. The Lyman-Kutcher-Burman (LKB) and cure models were then used to fit the incidence of radiation pneumonitis as a functionmore » of lung dose and other factors. Results: Total lung volumes with a sparing of less than 1854 cc at 40 Gy were associated with a significantly higher incidence of radiation pneumonitis at 6 months (38% vs 12% for patients with larger volumes, P<.001). This patient cohort was overwhelmingly female and represented 22% of the total female population of patients and nearly 30% of the cases of radiation pneumonitis. An LKB fit to normal tissue complication probability (NTCP) including volume as a dose modifying factor resulted in a dose that results in a 50% probability of complication for the smaller spared volume cohort that was 9 Gy lower than the fit to all mean lung dose data and improved the ability to predict radiation pneumonitis (P<.001). Using an effective dose parameter of n=0.42 instead of mean lung dose further improved the LKB fit. Fits to the data using the cure model produced similar results. Conclusions: Spared lung volume should be considered when treating NSCLC patients. Separate dose constraints based on smaller spared lung volume should be considered. Smaller spared lung volume patients should be followed closely for signs of radiation pneumonitis.« less

Bubonic and pneumonic plague - Uganda, 2006.

PubMed

2009-07-24

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

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

PubMed

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

2004-01-01

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

CT findings in hydrocarbon pneumonitis after diesel fuel siphonage.

PubMed

Yi, Mi Seon; Kim, Kun-Il; Jeong, Yeon Joo; Park, Hye Kyung; Lee, Min Ki

2009-10-01

The purpose of this study was to assess CT findings in a series of patients with hydrocarbon pneumonitis after diesel fuel siphonage. The characteristic CT findings of hydrocarbon pneumonitis after diesel fuel siphonage are the presence of air-space consolidations with predominant right middle lobe involvement and areas of low attenuation within consolidation. Occasionally, bronchoalveolar lavage is needed to confirm the diagnosis of hydrocarbon pneumonitis by the presence of lipid-laden macrophages on the basis of a history of diesel fuel aspiration.

The occupational exposure limit for fluid aerosol generated in metalworking operations: limitations and recommendations.

PubMed

Park, Donguk

2012-03-01

The aim of this review was to assess current knowledge related to the occupational exposure limit (OEL) for fluid aerosols including either mineral or chemical oil that are generated in metalworking operations, and to discuss whether their OEL can be appropriately used to prevent several health risks that may vary among metalworking fluid (MWF) types. The OEL (time-weighted average; 5 mg/m(3), short-term exposure limit ; 15 mg/m(3)) has been applied to MWF aerosols without consideration of different fluid aerosol-size fractions. The OEL, is also based on the assumption that there are no significant differences in risk among fluid types, which may be contentious. Particularly, the health risks from exposure to water-soluble fluids may not have been sufficiently considered. Although adoption of The National Institute for Occupational Safety and Health's recommended exposure limit for MWF aerosol (0.5 mg/m(3)) would be an effective step towards minimizing and evaluating the upper respiratory irritation that may be caused by neat or diluted MWF, this would fail to address the hazards (e.g., asthma and hypersensitivity pneumonitis) caused by microbial contaminants generated only by the use of water-soluble fluids. The absence of an OEL for the water-soluble fluids used in approximately 80-90 % of all applicants may result in limitations of the protection from health risks caused by exposure to those fluids.

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

PubMed

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

2016-02-19

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

Successful osimertinib rechallenge after osimertinib-induced pneumonitis in a patient with lung adenocarcinoma.

PubMed

Satoh, Shingo; Shiroyama, Takayuki; Tamiya, Motohiro; Nasu, Shingo; Tanaka, Ayako; Morita, Satomu; Morishita, Naoko; Suzuki, Hidekazu; Okamoto, Norio; Hirashima, Tomonori

2018-01-01

Pneumonitis is a serious adverse event of EGFR-TKI treatment. Although several cases of EGFR-TKI rechallenge after EGFR-TKI-induced pneumonitis have been reported, little is known about post-pneumonitis osimertinib rechallenge. We describe a 69-year-old never-smoking Japanese woman with postoperative recurrent lung adenocarcinoma retreated with osimertinib after osimertinib-induced pneumonitis. Although osimertinib rechallenge must be carefully chosen based on risk/benefit analysis, osimertinib rechallenge after osimertinib-induced pneumonitis may be an option, with limited alternative therapeutic options.

Current challenges in the development of vaccines for pneumonic plague

PubMed Central

Smiley, Stephen T

2008-01-01

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

Acute mercurial pneumonitis

PubMed Central

Milne, James; Christophers, Allen; Silva, Pamela De

1970-01-01

Milne, J., Christophers, A., and de Silva, Pamela (1970).Brit. J. industr. Med.,27, 334-338. Acute mercurial pneumonitis. Mercury vapour has been shown to cause acute effects on the lung when inhaled in high concentrations. Four men, exposed to mercury inside a tank, developed, hours later, signs and symptoms of an acute febrile illness with severe pulmonary irritation, characterized by fever, rigors, cough, dyspnoea, and tightness in the chest. A review of the literature revealed that this syndrome had been described and investigated previously in fewer than 20 cases during the past 40 years, and is apparently little known. Fatalities have been described, particularly in children, and necropsy evidence has consistently revealed the pattern of an acute diffuse interstitial pneumonitis, accompanied by profuse fibrinous exudation and erosion of the bronchial and bronchiolar lining. The two common features in all reports are the heating of mercury or the entering into a confined space, or both. Adequate respiratory protection by an efficient air-supplied respirator is mandatory in industrial circumstances of the kind described in this report. PMID:5488692

Pneumonic plague pathogenesis and immunity in Brown Norway rats.

PubMed

Anderson, Deborah M; Ciletti, Nancy A; Lee-Lewis, Hanni; Elli, Derek; Segal, Joshua; DeBord, Kristin L; Overheim, Katie A; Tretiakova, Maria; Brubaker, Robert R; Schneewind, Olaf

2009-03-01

The Brown Norway rat was recently described as a bubonic plague model that closely mimics human disease. We therefore evaluated the Brown Norway rat as an alternative small animal model for pneumonic plague and characterized both the efficacy and potency of vaccine candidates. When infected by intranasal instillation, these rats rapidly developed fatal pneumonic plague within 2 to 4 days of infection. Plague disease was characterized by severe alveolar edema and vascular hemorrhage in the lung in addition to fulminant necrotizing pneumonia caused by massive bacterial replication and inflammation. Twenty-four hours before death, animals developed systemic disease with an apparent delayed inflammatory response. We evaluated the ability of the protective antigen, LcrV, and a mutant derivative, V10, to protect these rats from pneumonic plague. Both were highly effective vaccines because complete protection was observed at challenge doses of 7500 LD(50). Antibody analyses suggested stronger potency of V10 immune sera compared with LcrV in the passive transfer of immunity to bubonic plague, with multiple neutralizing epitopes in LcrV. Taken together, these data demonstrate the effectiveness of inhibiting type III secretion in the prevention of pneumonic plague in rats and reveal critical contributions from both the cellular and humoral immune systems. Thus, the Brown Norway rat is an appealing alternative small animal model for the study of pneumonic plague pathogenesis and immunity.

Interstitial pneumonitis after acetylene welding: a case report.

PubMed

Brvar, Miran

2014-01-01

Acetylene is a colorless gas commonly used for welding. It acts mainly as a simple asphyxiant. In this paper, however, we present a patient who developed a severe interstitial pneumonitis after acetylene exposure during aluminum welding. A 44-year old man was welding with acetylene, argon and aluminum electrode sticks in a non-ventilated aluminum tank for 2 h. Four hours after welding dyspnea appeared and 22 h later he was admitted at the Emergency Department due to severe respiratory insufficiency with pO2 = 6.7 kPa. Chest X-ray showed diffuse interstitial infiltration. Pulmonary function and gas diffusion tests revealed a severe restriction (55% of predictive volume) and impaired diffusion capacity (47% of predicted capacity). Toxic interstitial pneumonitis was diagnosed and high-dose systemic corticosteroid methylprednisolone and inhalatory corticosteroid fluticasone therapy was started. Computed Tomography (CT) of the lungs showed a diffuse patchy ground-glass opacity with no signs of small airway disease associated with interstitial pneumonitis. Corticosteroid therapy was continued for the next 8 weeks gradually reducing the doses. The patient's follow-up did not show any deterioration of respiratory function. In conclusion, acetylene welding might result in severe toxic interstitial pneumonitis that improves after an early systemic and inhalatory corticosteroid therapy.

Turpentine-induced chemical pneumonitis with broncho-pleural fistula.

PubMed

Rodricks, A; Satyanarayana, M; D'Souza, G A; Ramachandran, P

2003-07-01

Turpentine is a volatile hydrocarbon used in polishes, solvents, paints and textile industry. When hydrocarbons are aspirated into the lung, they cause chemical pneumonitis, acute respiratory distress syndrome (ARDS), and rarely pneumatoceles and pneumothorax. We report a 20-year old boy with turpentine-induced chemical pneumonitis that evolved into a bronchopleural fistula. He was treated with oxygen, steroids and intercostal tube drainage. This is the first reported case of turpentine-associated bronchopleural fistula.

Hypersensitivity reactions to non-steroidal anti-inflammatory drugs.

PubMed

Cornejo-Garcia, José Antonio; Blanca-López, Natalia; Doña, Inmaculada; Andreu, Inmaculada; Agúndez, José A G; Carballo, Miguel; Blanca, Miguel; Canto, María Gabriela

2009-11-01

NSAIDs are the most important group of drugs involved in hypersensitivity drug reactions, and include heterogeneous compounds with very different chemical structures. These reactions can be IgE dependent (immediate reactions), T cell-mediated (non-immediate), or induced by a non-specific immunological mechanism related with the blocking of the COX-1 enzyme and the shunting to the lipooxygenase pathway (cross-intolerant reactions). Cutaneous symptoms are the most frequent, with ibuprofen, naproxen and diclofenac being common culprit drugs worldwide, although others can be involved because patterns of consumption and exposure rates vary between countries. A very important proportion of immunological reactions are immediate, with urticaria and anaphylaxis being the typical clinical manifestations. Non-immediate reactions comprise a number of heterogeneous entities ranging from mild exanthema to severe TEN or DRESS syndrome, as well as organ-specific reactions such as hepatitis or pneumonitis. Cross-intolerant reactions appear to non-chemically related drugs, and involve respiratory airways, skin or both. In vivo diagnostic tests are based on the capacity of the skin to respond to the culprit drug, but their sensitivity is in many instances rather low. The approach for in vitro testing consists of either detecting specific IgE antibodies or studying the proliferation of T lymphocytes toward the eliciting drug. No appropriate tests are yet available for the in vitro validation of cross-intolerance reactions, although techniques based on the stimulation of basophils have been proposed. Based on these findings, the diagnostic approach is often based on the controlled administration of the drug to assess tolerance. In this work we review current knowledge on hypersensitivity reactions to NSAIDs, including diagnostic approach and genetic studies.

Occupational asthma due to formaldehyde.

PubMed Central

Burge, P S; Harries, M G; Lam, W K; O'Brien, I M; Patchett, P A

1985-01-01

Bronchial provocation studies on 15 workers occupationally exposed to formaldehyde are described. The results show that formaldehyde exposure can cause asthmatic reactions, and suggest that these are sometimes due to hypersensitivity and sometimes to a direct irritant effect. Three workers had classical occupational asthma caused by formaldehyde fumes, which was likely to be due to hypersensitivity, with late asthmatic reactions following formaldehyde exposure. Six workers developed immediate asthmatic reactions, which were likely to be due to a direct irritant effect as the reactions were shorter in duration than those seen after soluble allergen exposure and were closely related to histamine reactivity. The breathing zone concentrations of formaldehyde required to elicit these irritant reactions (mean 4.8 mg/m3) were higher than those encountered in buildings recently insulated with urea formaldehyde foam, but within levels sometimes found in industry. Images PMID:4023975

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

Code of Federal Regulations, 2011 CFR

2011-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Chlamydia Psittaci Vaccine (Feline... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall be...

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Chlamydia Psittaci Vaccine (Feline... VECTORS STANDARD REQUIREMENTS Live Bacterial Vaccines § 113.71 Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia. Chlamydia Psittaci Vaccine (Feline Pneumonitis), Live Chlamydia, shall be...

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

Code of Federal Regulations, 2014 CFR

2014-01-01

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

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

PubMed

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

2018-01-01

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

Associated factors of radiation pneumonitis induced by precise radiotherapy in 186 elderly patients with esophageal cancer.

PubMed

Cui, Zhen; Tian, Ye; He, Bin; Li, Hongwei; Li, Duojie; Liu, Jingjing; Cai, Hanfei; Lou, Jianjun; Jiang, Hao; Shen, Xueming; Peng, Kaigui

2015-01-01

Radiation pneumonitis is one of the most severe complications of esophageal cancer. To explore the factors correlated to radiation pneumonitis induced by precise radiotherapy for elderly patients with esophageal cancer. The retrospective analysis was used to collect clinical data from 186 elderly patients with esophageal cancer. The incidence of radiation pneumonitis was observed, followed by statistical analysis through ANVON or multiple regression analysis. 27 in 186 cases of esophageal cancer suffered from radiation pneumonitis, with incidence of 14.52%. The single factor analysis showed that, Karnofsky performance status (KPS) score, chronic obstructive pulmonary disease, concurrent chemoradiotherapy, gross tumor volume (GTV) dose, lung V20, mean lung dose (MLD) and planning target volume (PTV) were associated with radiation pneumonitis. The logistic regression analysis indicated that, concurrent chemoradiotherapy, GTV dose, lung V20 and PTV were the independent factors of radiation pneumonitis. The concurrent chemoradiotherapy, GTV dose, lung V20, MLD and PTV are the major risk factors of radiation pneumonitis for elderly patients with esophageal cancer.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palma, David A., E-mail: david.palma@uwo.ca; Senan, Suresh; Tsujino, Kayoko

2013-02-01

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

Trichloroethylene Hypersensitivity Syndrome Is Potentially Mediated through Its Metabolite Chloral Hydrate.

PubMed

Huang, Yongshun; Xia, Lihua; Wu, Qifeng; Zeng, Zifang; Huang, Zhenlie; Zhou, Shanyu; Jin, Jiachun; Huang, Hanlin

2015-01-01

We documented previously the entity of trichloroethylene (TCE) hypersensitivity syndrome (THS) in occupational workers. To identify the culprit causative compound, determine the type of hypersensitivity of THS, and establish a screening test for subjects at risk of THS. TCE and its main metabolites chloral hydrate (CH), trichloroethanol (TCOH) and trichloroacetic acid (TCA) were used as allergens at different concentrations in skin patch tests. The study included 19 case subjects diagnosed with occupational THS, 22 control healthy workers exposed to TCE (exposure >12 weeks), and 20 validation new workers exposed to TCE for <12 weeks free of THS. All subjects were followed-up for 12 weeks after the patch test. The highest patch test positive rate in subjects with THS was for CH, followed by TCOH, TCA and TCE. The CH patch test positive rate was 100% irrespective of CH concentrations (15%, 10% and 5%). The TCOH patch test positive rate was concentration-dependent (89.5%, 73.7% and 52.6% for 5%, 0.5% and 0.05%, respectively). Lower patch test positive rates were noted for TCA and TCE. All patch tests (including four allergens) were all negative in each of the 22 control subjects. None of the subjects of the validation group had a positive 15% CH patch test. Chloral hydrate seems to be the culprit causative compound of THS and type IV seems to be the major type of hypersensitivity of THS. The CH patch test could be potentially useful for screening workers at risk of THS.

Trichloroethylene Hypersensitivity Syndrome Is Potentially Mediated through Its Metabolite Chloral Hydrate

PubMed Central

Huang, Yongshun; Xia, Lihua; Wu, Qifeng; Zeng, Zifang; Huang, Zhenlie; Zhou, Shanyu; Jin, Jiachun; Huang, Hanlin

2015-01-01

Background We documented previously the entity of trichloroethylene (TCE) hypersensitivity syndrome (THS) in occupational workers. Objectives To identify the culprit causative compound, determine the type of hypersensitivity of THS, and establish a screening test for subjects at risk of THS. Methods TCE and its main metabolites chloral hydrate (CH), trichloroethanol (TCOH) and trichloroacetic acid (TCA) were used as allergens at different concentrations in skin patch tests. The study included 19 case subjects diagnosed with occupational THS, 22 control healthy workers exposed to TCE (exposure >12 weeks), and 20 validation new workers exposed to TCE for <12 weeks free of THS. All subjects were followed-up for 12 weeks after the patch test. Results The highest patch test positive rate in subjects with THS was for CH, followed by TCOH, TCA and TCE. The CH patch test positive rate was 100% irrespective of CH concentrations (15%, 10% and 5%). The TCOH patch test positive rate was concentration-dependent (89.5%, 73.7% and 52.6% for 5%, 0.5% and 0.05%, respectively). Lower patch test positive rates were noted for TCA and TCE. All patch tests (including four allergens) were all negative in each of the 22 control subjects. None of the subjects of the validation group had a positive 15% CH patch test. Conclusions Chloral hydrate seems to be the culprit causative compound of THS and type IV seems to be the major type of hypersensitivity of THS. The CH patch test could be potentially useful for screening workers at risk of THS. PMID:26020924

Pneumonitis in Adult Onset Still's Disease: Uncommon or Under Diagnosed?

PubMed

Fernandes, Silvia; Almeida, Margarida; Pereira da Silva, José Alberto; Romeu, José Carlos

2017-08-31

The adult onset Still's Disease is an uncommon entity characterized by multiple clinical manifestations. Pneumonitis, less often considered, deserves particular emphasis given the need for differential diagnosis and because it can progress to severe respiratory failure. With the aim to highlight the pulmonary parenchyma involvement in patients with adult onset Still's Disease, we present a case report which progresses with pneumonitis.

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. Copyright 2010 S. Karger AG, Basel.

Antibiotic Treatment of Experimental Pneumonic Plague in Mice

PubMed Central

Byrne, William R.; Welkos, Susan L.; Pitt, M. Louise; Davis, Kelly J.; Brueckner, Ralf P.; Ezzell, John W.; Nelson, Gene O.; Vaccaro, Joseph R.; Battersby, Luann C.; Friedlander, Arthur M.

1998-01-01

A mouse model was developed to evaluate the efficacy of antibiotic treatment of pneumonic plague; streptomycin was compared to antibiotics with which there is little or no clinical experience. Infection was induced by inhalation of aerosolized Yersinia pestis organisms. Antibiotics were administered by intraperitoneal injection every 6 hours for 5 days, at doses that produced levels of drug in serum comparable to those observed in humans treated for other serious infections. These studies compared in vitro to in vivo activity and evaluated the efficacy of antibiotics started at different times after exposure. Early treatment (started 24 h after challenge, when 0 of 10 mice tested had positive blood cultures) with netilmicin, ciprofloxacin, ofloxacin, ceftriaxone, ceftazidime, aztreonam, ampicillin, and rifampin (but not cefazolin, cefotetan, or ceftizoxime) demonstrated efficacy comparable to streptomycin. Late treatment (started 42 h after exposure, when five of five mice tested had positive blood cultures) with netilmicin, ciprofloxacin, ofloxacin, and a high dose (20 mg/kg of body weight every 6 h) of gentamicin produced survival rates comparable to that with streptomycin, while all of the beta-lactam antibiotics (cefazolin, cefotetan, ceftriaxone, ceftazidime, aztreonam, and ampicillin) and rifampin were significantly inferior to streptomycin. In fact, all groups of mice treated late with beta-lactam antibiotics experienced accelerated mortality rates compared to normal-saline-treated control mice. These studies indicate that netilmicin, gentamicin, ciprofloxacin, and ofloxacin may be alternatives for the treatment of pneumonic plague in humans. However, the beta-lactam antibiotics are not recommended, based upon poor efficacy in this mouse model of pneumonic plague, particularly when pneumonic plague may be associated with bacteremia. PMID:9517950

Biomarkers for Radiation Pneumonitis Using Noninvasive Molecular Imaging.

PubMed

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

2016-08-01

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

Pulmonary health effects of agriculture.

PubMed

Nordgren, Tara M; Bailey, Kristina L

2016-03-01

Occupational exposures in the agricultural industry are associated with numerous lung diseases, including chronic obstructive pulmonary disease, asthma, hypersensitivity pneumonitis, lung cancer, and interstitial lung diseases. Efforts are ongoing to ascertain contributing factors to these negative respiratory outcomes and improve monitoring of environmental factors leading to disease. In this review, recently published studies investigating the deleterious effects of occupational exposures in the agricultural industry are discussed. Occupational exposures to numerous agricultural environment aerosols, including pesticides, fungi, and bacteria are associated with impaired respiratory function and disease. Increases in certain farming practices, including mushroom and greenhouse farming, present new occupational exposure concerns. Improved detection methods may provide opportunities to better monitor safe exposure levels to known lung irritants. In the agricultural industry, occupational exposures to organic and inorganic aerosols lead to increased risk for lung disease among workers. Increased awareness of respiratory risks and improved monitoring of agricultural environments are necessary to limit pulmonary health risks to exposed populations.

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

PubMed

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

2017-10-01

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

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

PubMed Central

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

2017-01-01

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

DELAYED HYPERSENSITIVITY

PubMed Central

Uhr, Jonathan W.; Salvin, S. B.; Pappenheimer, A. M.

1957-01-01

A general method for induction of the delayed hypersensitive state directed against single protein antigens is described. The method consists of intradermal injection of minute amounts of washed immune precipitates containing the antigen in question. Provided the specific precipitates are formed in the region of antibody excess, maximal sensitivity develops at least 2 to 3 weeks before detectable circulating antibody is formed in guinea pigs against the sensitizing antigen. Neither adjuvant nor killed acid-fast bacteria are required for induction of the delayed hypersensitive state although the degree of sensitization is considerably increased when the sensitizing material is incorporated in Freund's complete adjuvant. Characteristics of the "delayed" as opposed to the "immediate" hypersensitive states in the guinea pig are described and implications of the findings are discussed. PMID:13385403

Hypersensitivity reactions to etoposide.

PubMed

Hoetelmans, R M; Schornagel, J H; ten Bokkel Huinink, W W; Beijnen, J H

1996-04-01

To report a hypersensitivity reaction to etoposide occurring in a patient after 2 months of drug therapy. A 20-year-old man with a diagnosis of testicular carcinoma was treated with bleomycin, etoposide, and cisplatin (BEP regimen). After dose 20 of etoposide, an exanthema was noted, which was attributed to etoposide. The patient had received 19 doses of etoposide during the previous 2 months without any sign of an allergic reaction. Rechallenging the patient with etoposide from another batch resulted in recurrence of the exanthema. Both etoposide and its excipient (polysorbate 80) are suspected of causing hypersensitivity reactions. Although the exact mechanism of the hypersensitivity reaction is not known, it is believed to be of nonimmunogenic origin. With a lower rate of infusion of etoposide and/or by premedication with antihistamines and/or corticosteroids, hypersensitivity reactions to etoposide might be prevented in patients with a history of hypersensitivity to this drug.

Risk Analysis of Pneumonitis in Taxane Therapy After Chemoradiotherapy for Patients With Metastatic or Recurrent Esophageal Cancer.

PubMed

Kishida, Yoshihiro; Tsushima, Takahiro; Endo, Masahiro; Hamauchi, Satoshi; Todaka, Akiko; Yokota, Tomoya; Machida, Nozomu; Yamazaki, Kentaro; Fukutomi, Akira; Onozawa, Yusuke; Yasui, Hirofumi

2018-01-01

Taxane chemotherapy for esophageal cancer causes pneumonitis, not only by itself but also by radiation recall. This study aimed to clarify the risk of pneumonitis in patients with esophageal cancer who receive taxane therapy after chemoradiotherapy. The data of 129 patients with metastatic or recurrent esophageal cancer who initiated taxane therapy between September 2002 and June 2013 were retrospectively analyzed. Patient selection criteria were as follows: performance status ≤2, preserved organ functions, previous chemoradiotherapy with a radiation dose of ≥50 Gy, grade 0 or 1 pneumonitis at taxane initiation, and no concomitant malignancy. Logistic regression analysis was performed to identify risk factors for pneumonitis. Patient characteristics were as follows: males/females, 116/13; median age, 63 years (range, 44 to 80 y); performance status of 0/1/2, 61/60/8; smoking history, 112 (88%); location of the primary tumor Ce/Ut/Mt/Lt/Ae 12/30/66/20/1; median radiation dose, 60 Gy; history of radiation pneumonitis, 39 (30%); history of other pulmonary disease, 4 (3%); and median duration between the last radiation therapy (RT) exposure and taxane initiation, 6.1 months (range, 1.0 to 71 mo). During the median observation period of 7.8 months from taxane initiation, the incidence of grade 2 and 3 pneumonitis was observed in 7 (5.4%) and 3 (2.3%) patients, respectively. No patient died of pneumonitis. The only independent risk factor for pneumonitis was a ≤4-month period between the last RT exposure and taxane initiation (P=0.03). A short period between the last RT exposure and taxane initiation is an independent risk factor for pneumonitis development.

Pneumonic Plague in Johannesburg, South Africa, 1904

PubMed Central

Egan, Joseph R.; Hall, Ian

2018-01-01

Plague is a potentially dangerous reemerging disease. Because modern outbreaks are relatively infrequent, data for epidemiologic study are best found in historical accounts. In 1905, the Rand Plague Committee published a report describing an explosive outbreak of 113 cases of pneumonic plague that occurred in Johannesburg, South Africa, in 1904. Using these data, we investigated social, spatial, and temporal dynamics and quantified transmissibility as measured by the time-varying reproduction number. Risk for transmission was highest when friends, family members, and caregivers approached the sick. Reproduction numbers were 2–4. Transmission rates rapidly diminished after implementation of control measures, including isolation and safer burial practices. A contemporaneous smaller bubonic plague outbreak associated with a low-key epizootic of rats also occurred. Clusters of cases of pneumonic plague were mostly limited to the Indian community; cases of bubonic plague were mostly associated with white communities and their black African servants.

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

NASA Astrophysics Data System (ADS)

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

2009-02-01

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

Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lingos, T.I.; Recht, A.; Vicini, F.

1991-07-01

The likelihood of radiation pneumonitis and factors associated with its development in breast cancer patients treated with conservative surgery and radiation therapy have not been well established. To assess these, the authors retrospectively reviewed 1624 patients treated between 1968 and 1985. Median follow-up for patients without local or distant failure was 77 months. Patients were treated with either tangential fields alone (n = 508) or tangents with a third field to the supraclavicular (SC) or SC-axillary (AX) region (n = 1116). Lung volume treated in the tangential fields was generally limited by keeping the perpendicular distance (demagnified) at the isocentermore » from the deep field edges to the posterior chest wall (CLD) to 3 cm or less. Seventeen patients with radiation pneumonitis were identified (1.0%). Radiation pneumonitis was diagnosed when patients presented with cough (15/17, 88%), fever (9/17, 53%), and/or dyspnea (6/17, 35%) and radiographic changes (17/17) following completion of RT. Radiographic infiltrates corresponded to treatment portals in all patients, and in 12 of the 17 patients, returned to baseline within 1-12 months. Five patients had permanent scarring on chest X ray. No patient had late or persistent pulmonary symptoms. The incidence of radiation pneumonitis was correlated with the combined use of chemotherapy (CT) and a third field. Three percent (11/328) of patients treated with a 3-field technique who received chemotherapy developed radiation pneumonitis compared to 0.5% (6 of 1296) for all other patients (p = 0.0001). When patients treated with a 3-field technique received chemotherapy concurrently with radiation therapy, the incidence of radiation pneumonitis was 8.8% (8/92) compared with 1.3% (3/236) for those who received sequential chemotherapy and radiation therapy (p = 0.002).« less

Pneumonic Plague Transmission, Moramanga, Madagascar, 2015.

PubMed

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

2017-03-01

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

Symptomatic Radiation Pneumonitis After Accelerated Partial Breast Irradiation Using Three-dimensional Conformal Radiotherapy.

PubMed

Shikama, Naoto; Kumazaki, Y U; Miyazawa, Kazunari; Miyaura, Kazunori; Kato, Shingo; Nakamura, Naoki; Kawamori, Jiro; Shimizuguchi, Takuya; Saito, Naoko; Saeki, Toshiaki

2016-05-01

To examine the relationship between symptomatic radiation pneumonitis and lung dose-volume parameters for patients receiving accelerated partial breast irradiation (APBI) using three dimensional-conformal radiotherapy (3D-CRT). The prescribed radiation dose was 30 Gy in 5 fractions over 10 days. Toxicity was graded according to the Common Terminology Criteria for Adverse Events (version 4.0). Fifty-five patients were enrolled from August 2010 to October 2013 and the median follow-up time was 30 months (range=18-46 months). Three patients (5%) developed grade 2 symptomatic radiation pneumonitis after 3D-CRT APBI. Among 16 patients with ILV10Gy (% ipsilateral lung receiving ≥10 Gy) of 10% or higher, three patients (19%) developed symptomatic radiation pneumonitis. This trend was not observed in any of the patients with ILV10Gy less than 10% (p=0.005). High ILV10Gy might be associated with symptomatic radiation pneumonitis after 3D-CRT APBI. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Biomarkers for radiation pneumonitis using non-invasive molecular imaging

PubMed Central

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

2016-01-01

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

Expectations and effectiveness of medical treatment and classical homeopathic treatment for patients with hypersensitivity illnesses--one year prospective study.

PubMed

Launsø, Laila; Henningsen, Inge; Rieper, Jonas; Brender, Henriette; Sandø, Finn; Hvenegaard, Anne

2007-10-01

To describe and compare characteristics of adult patients who received treatment for hypersensitivity illnesses by general practitioners (GPs) and classical homeopaths (CHs) over a period of 1 year and examine the statistical predictors of self-reported treatment outcomes. We conducted a survey on 151 Danish adult patients with hypersensitivity illnesses, who chose treatment from one of 13 GPs or one of 10 CHs who participated in the project. The treatments were given as individual packages in the naturalistic clinical setting. Patients completed questionnaires at start of treatment, after 6 months and a year after start of treatment. Response rates for the first, second and third questionnaire were respectively 68%, 98%, 95% for the GP patients and 82%, 98%, 94% for the CH patients. Patients seeking CH treatment in this study are significantly different in gender and education from patients seeking GP treatment. We did not find significant differences in terms of occupational training, occupation, sickness absence due to hypersensitivity illnesses, diseases other than hypersensitivity illnesses, symptoms severity due to hypersensitivity illnesses before treatment and expectation of the ability of the treatment to alleviate symptoms. Eighty-eight percent of GP and 21% of CH patients were continuing treatment after 1 year. Regression analysis showed that the only significant independent variables to explain the probability of obtaining very positive effect or cure for GPs and CHs were that the patients were in 'maintenance treatment', and had high expectation before treatment of the ability of the treatment to relieve their symptoms. In this study self-reported very positive effect of GP treatment and very positive effect and cure of CH treatment are associated with the patients' high expectation of the treatment and continuation of maintenance treatment.

Detection of CMV pneumonitis after lung transplantation using PCR of DNA from bronchoalveolar lavage cells.

PubMed

Bewig, B; Haacke, T C; Tiroke, A; Bastian, A; Böttcher, H; Hirt, S W; Rautenberg, P; Haverich, A

2000-01-01

Cytomegalovirus (CMV) is known as a common pathogen causing infections after lung transplantation. Rapid diagnosis of CMV infection is important for the initiation of a specific treatment. Evaluation of methods for the rapid diagnosis of CMV pneumonitis. The detection rates of CMV DNA in bronchoalveolar lavage (BAL) and bronchial brushes by polymerase chain reaction (PCR), of viral antigens (p52 and IE1) in BAL and of pp65 antigen in peripheral blood leukocytes were compared to the clinical status after lung transplantation. In 28 patients, 105 BAL, 96 blood samples and 14 brushes were analyzed. In 6 patients, a total of eight episodes of CMV pneumonitis occurred. Five of the 6 with positive CMV antigens in BAL (p52 or IE1) showed signs of CMV pneumonitis. All episodes of CMV pneumonitis were detected by the PCR of BAL cells. Fourteen samples positive for CMV pp65 antigen in blood were negative in BAL PCR. In these cases, no clinical signs of pulmonary CMV infection occurred. Overall sensitivity, specificity, and positive and negative predictive values for the detection of CMV pneumonitis by PCR of BAL cells were 100, 98.9, 88.9 and 100%, respectively. In brush samples, PCR did not provide additional information to the results of the PCR of BAL cells. PCR of DNA from BAL cells is suitable for reliable and rapid detection of CMV pneumonitis. Copyright 2000 S. Karger AG, Basel.

Pneumonic Plague Transmission, Moramanga, Madagascar, 2015

PubMed Central

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

2017-01-01

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

Metronidazole hypersensitivity.

PubMed

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

1994-03-01

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

IgE-mediated hypersensitivity reactions to cannabis in laboratory personnel.

PubMed

Herzinger, T; Schöpf, P; Przybilla, B; Ruëff, F

2011-01-01

There have been sporadic reports of hypersensitivity reactions to plants of the Cannabinaceae family (hemp and hops), but it has remained unclear whether these reactions are immunologic or nonimmunologic in nature. We examined the IgE-binding and histamine-releasing properties of hashish and marijuana extracts by CAP-FEIA and a basophil histamine release test. Two workers at a forensic laboratory suffered from nasal congestion, rhinitis, sneezing and asthmatic symptoms upon occupational contact with hashish or marijuana, which they had handled frequently for 25 and 16 years, respectively. Neither patient had a history of atopic disease. Serum was analyzed for specific IgE antibodies to hashish or marijuana extract by research prototype ImmunoCAP, and histamine release from basophils upon exposure to hashish or marijuana extracts was assessed. Results were matched to those of 4 nonatopic and 10 atopic control subjects with no known history of recreational or occupational exposure to marijuana or hashish. Patient 1 had specific IgE to both hashish and marijuana (CAP class 2), and patient 2 to marijuana only (CAP class 2). Controls proved negative for specific IgE except for 2 atopic individuals with CAP class 1 to marijuana and 1 other atopic individual with CAP class 1 to hashish. Stimulation of basophils with hashish or marijuana extracts elicited histamine release from basophils of both patients and 4 atopic control subjects. Our results suggest an IgE-related pathomechanism for hypersensitivity reactions to marijuana or hashish. Copyright © 2011 S. Karger AG, Basel.

Ovine Mannheimia haemolytica isolates from lungs with and without pneumonic lesions belong to similar genotypes.

PubMed

García-Alvarez, Andrés; Fernández-Garayzábal, José Francisco; Chaves, Fernando; Pinto, Chris; Cid, Dolores

2018-06-01

This study investigated the genetic characteristics of 121 ovine Mannheimia haemolytica isolates from lungs with (n = 75) and without pneumonic lesions (n = 46) using multilocus sequence typing (MLST), virulence-associated gene typing and pulsed-field gel electrophoresis (PFGE). Twelve STs were identified with most isolates (81%) belonged to ST16, ST28 and ST8. Analysis of the M. haemolytica MLST Database indicate a wide distribution of these genotypes in small ruminants, never reported in bovine isolates. This could suggest the adaptation of certain genetic lineages of M. haemolytica to small ruminants. e-BURST analysis grouped most STs into three clonal complexes (CC2, CC8 and CC28), consistent with a clonal population structure of M. haemolytica. Virulence-associated gene typing identified five virulence profiles in 64% and 65.1% of the M. haemolytica isolates from lungs with and without pneumonic lesions, respectively. These data suggest that M. haemolytica isolates from the lungs with and without pneumonic lesions are genetically homogeneous. By PGFE analysis a high level of genetic diversity was observed not only within isolates from lungs without pneumonic lesions but also among isolates from pneumonic lesions (GD 0.69 and GD 0.66, respectively; P > 0.05). These results indicate that multiple strains of M. haemolytica may be associated with individual cases of pneumonia in sheep. Copyright © 2018 Elsevier B.V. All rights reserved.

[Immune-related pneumonitis caused by programmed death-1 inhibitor Pembrolizumab: a case report and literature review].

PubMed

Chen, Y L; Zhao, J; Jia, R; Wang, H Y; Zheng, J; Bai, C Q; Wang, M Z; Xu, J M

2017-10-12

Objective: To investigate the risk factors, clinical manifestations, radiological features, diagnosis, treatment and prognosis of immune-related pneumonitis caused by programmed death-1(PD-1)/PD-L1 inhibitors. Methods: The clinical data of immune-related pneumonitis caused by PD-1 inhibitor Pembrolizumab in a patient with advanced esophageal carcinoma admitted to the 307(th) Hospital of Chinese People's Liberation Army was retrospectively analyzed and the related literatures were reviewed. We searched Medline database using the keywords"PD-1 inhibitor","PD-L1 inhibitor","Pembrolizumab","Nivolumab","Atezolizumab"combined with"Pneumonitis"by Mar 31, 2017. Results: The patient was a 60-year-old male presented with progression disease after surgery, local radiation and couples of chemotherapy for his esophageal carcinoma. Then pembrolizumab, a kind of PD-l inhibitors, was given intravenously every 3 weeks with the average dosage 3 mg per kg. After six cycles of pembrolizumab, the patient began to have fever, cough and dyspnea, which aggravated gradually. Chest CT showed diffuse ground glass opacity, exudation and consolidation in both lungs and little pleural effusion in the right side. Cellular interstitial pneumonitis was confirmed by pathological examination. The patient's symptoms were alleviated after enough steroids and chest CT showed pulmonary infiltration was also absorbed. But the pneumonitis reoccurred twice after stopping or tapering steroids quickly and could also be controlled by using steroids again. Now the patient was still given steroids treatment and the primary esophageal cancer remained stable. 14 articles were retrieved and 88 cases of immune-related pneumonitis caused by PD-1/PD-L1 inhibitors were reported. Among these 89 cases with immune-related pneumonitis, both male and female could attack and the median age was 67 years old. Most cases were grade 1 or 2. The common clinical manifestations were dyspnea, cough, fever and other immune

Dietary hypersensitivity in cats and dogs.

PubMed

Mandigers, Paul; German, Alexander J

2010-10-01

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

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

PubMed

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

2016-11-01

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

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

PubMed

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

2015-01-01

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

Can lung function measurements be used to predict which patients will be at risk of developing interstitial pneumonitis after bone marrow transplantation?

PubMed

Milburn, H J; Prentice, H G; du Bois, R M

1992-06-01

Lung function often deteriorates after bone marrow transplantation for haematological malignancies. Whether pulmonary function measurements are useful for monitoring patients' progress after transplantation and for alerting clinicians to the development of pneumonitis is uncertain. Serial pulmonary function measurements were made in 39 patients with a haematological malignancy, and the values from 18 recipients of T cell depleted allogeneic (n = 17) or autologous (n = 1) bone marrow transplants who developed interstitial pneumonitis were compared retrospectively with values from 21 recipients of allogeneic (n = 17) or autologous (n = 4) transplants who did not develop pneumonitis. Lung function was measured at the onset of a further 18 episodes of pneumonitis. Measurements made before transplantation showed no difference in forced expiratory volume in one second (FEV1), transfer factor for carbon monoxide (TLCO), or total lung capacity between the two groups, but the forced vital capacity (FVC) was slightly higher in those who developed pneumonitis (mean (SD)% predicted 104 (12)) than in those who did not (93 (17%)). Six weeks and three months after transplantation all pulmonary function measurements had fallen slightly in both groups but TLCO had fallen considerably more in those who later developed pneumonitis, being 71% (SD 11%) and 77% (7%) of pretransplant values in patients who later developed pneumonitis compared with 109% (38%) and 96% (26%) in those who did not. All lung function measurements were significantly lower at the onset of pneumonitis than three months after transplantation, even in patients with no abnormal signs and a normal chest radiograph. Serial measurements of gas transfer before and after bone marrow transplantation may be useful for predicting which patients will be at risk of developing pneumonitis and may help to diagnose pneumonitis in breathless patients with no abnormal signs.

Hypersensitivity reactions in patients receiving hemodialysis.

PubMed

Butani, Lavjay; Calogiuri, Gianfranco

2017-06-01

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

Levofloxacin Cures Experimental Pneumonic Plague in African Green Monkeys

PubMed Central

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

2011-01-01

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

Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allen, Aaron M.; Czerminska, Maria; Jaenne, Pasi A.

2006-07-01

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

Oral administration of herbal medicines for radiation pneumonitis in lung cancer patients: A systematic review and meta-analysis

PubMed Central

Baek, Hyunjung; Kim, Jae-Hyo; Lee, Beom-Joon

2018-01-01

Background Radiation pneumonitis is a common and serious complication of radiotherapy. Many published randomized controlled studies (RCTs) reveal a growing trend of using herbal medicines as adjuvant therapy to prevent radiation pneumonitis; however, their efficacy and safety remain unexplored. Objective The aim of this systematic review is to evaluate the efficacy and safety of herbal medicines as adjunctive therapy for the prevention of radiation pneumonitis in patients with lung cancer who undergo radiotherapy. Methods We searched the following 11 databases: three English medical databases [MEDLINE (PubMed), EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL)], five Korean medical databases (Korean Studies Information, Research information Service System, KoreaMed, DBPIA, National Digital Science Library), and three Chinese medical databases [the China National Knowledge Database (CNKI), Journal Integration Platform (VIP), and WanFang Database]. The primary outcome was the incidence of radiation pneumonitis. The risk of bias was assessed using the Cochrane risk-of-bias tool. Results Twenty-two RCTs involving 1819 participants were included. The methodological quality was poor for most of the studies. Meta-analysis showed that herbal medicines combined with radiotherapy significantly reduced the incidence of radiation pneumonitis (n = 1819; RR 0.53, 95% CI 0.45–0.63, I2 = 8%) and the incidence of severe radiation pneumonitis (n = 903; RR 0.22, 95% CI 0.11–0.41, I2 = 0%). Combined therapy also improved the Karnofsky performance score (n = 420; WMD 4.62, 95% CI 1.05–8.18, I2 = 82%). Conclusion There is some encouraging evidence that oral administration of herbal medicines combined with radiotherapy may benefit patients with lung cancer by preventing or minimizing radiation pneumonitis. However, due to the poor methodological quality of the identified studies, definitive conclusion could not be drawn. To confirm the merits of this approach

Occupational contact allergy to omeprazole and ranitidine.

PubMed

Herrera-Mozo, Inmaculada; Sanz-Gallen, Pere; Martí-Amengual, Gabriel

2017-05-16

Omeprazole is a proton pump inhibition and ranitidine is an H2 histamine receptor antagonist widely used in the treatment of gastroesophageal reflex disease, peptic ulcer disease, Zollinger-Ellison syndrome and as a protector of the gastric mucosae. We report a case of occupational contact allergy to omeprazole and ranitidine. A 48-year-old man, with no pre-existing history of atopy or lifestyle factors. He neither had any medical history of consumption of drugs such as ranitidine and omeprazole. He worked for 19 months in the pharmaceutical company that manufactured ranitidine base. He presented rash in the face and eczema on the dorsum of the hands with itching. The study by prick tests with ranitidine gave negative response. Patch testing with ranitidine base and ranitidine hydrochloride gave positive response. A month later, when the patient was asymptomatic he returned to the pharmaceutical company, being switched from this previous job to the reactor manufacturing omeprazole. A few days after that, he presented erythematous eruptions involving face and neck with itching. Prick tests, path tests and in vitro laboratories studies with omeprazole gave positives. In this case the patient presented hypersensitivity type I at omeprazole and hypersensitivity type IV at omeprazole and ranitidine. Our aportation indicates the importance of careful analysis of the occupational exposure histories of patients with the suspected type I or type IV hypersensitivity to allergens, to determine whether work exposure is the cause. Med Pr 2017;68(3):433-435. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Risk Factors Associated With Symptomatic Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer.

PubMed

Shi, Shiming; Zeng, Zhaochong; Ye, Luxi; Huang, Yan; He, Jian

2017-06-01

Radiation pneumonitis is the most frequent acute pulmonary toxicity following stereotactic body radiation therapy for lung cancer. Here, we investigate clinical and dosimetric factors associated with symptomatic radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy. A total of 67 patients with stage I non-small cell lung cancer who received stereotactic body radiation therapy at our institution were enrolled, and their clinicopathological parameters and dosimetric parameters were recorded and analyzed. The median follow-up period was 26.4 months (range: 7-48 months). In univariate analysis, tumor size ( P = .041), mean lung dose ( P = .028), V2.5 ( P = .024), V5 ( P = .014), V10 ( P = .004), V20 ( P = .024), V30 ( P = .020), V40 ( P = .040), and V50 ( P = 0.040) were associated with symptomatic radiation pneumonitis. In multivariable logistic regression analysis, V10 ( P = .049) was significantly associated with symptomatic radiation pneumonitis. In conclusion, this study found that tumor size, mean lung dose, and V2.5 to V50 were risk factors markedly associated with symptomatic radiation pneumonitis. Our data suggested that lung V10 was the most significant factor, and optimizing lung V10 may reduce the risk of symptomatic radiation pneumonitis. For both central and peripheral stage I lung cancer, rate of radiation pneumonitis ≥grade 2 was low after stereotactic body radiation therapy with appropriate fraction dose.

Effects of proton pump inhibitors on lung cancer precise radiotherapy-induced radiation pneumonitis.

PubMed

Su, QiaoLi; Wang, Duoning; Yuan, Bo; Liu, Feng; Lei, Yi; Li, Shuangqing

2014-11-01

The objective of this study was to explore the effects of proton pump inhibitors (PPIs) on the development and prognosis of lung cancer precise radiotherapy-induced radiation pneumonitis. Clinical materials of 84 lung cancer patients who had radiation pneumonitis after precise radiotherapy were retrospectively analyzed, and the patients were divided into PPI group and control group, according to whether or not PPIs were applied. The development and prognosis of patients and the effects of different doses of PPI on patient condition from two groups were compared. There were 57 PPI cases in PPI group and 27 cases in control group. Basic characteristics of patients were not statistically different between the two groups; however, white blood cell count, oxygenation indexes, blood gas pH, and lung imaging index were significantly different (p < 0.05), indicating that radiation pneumonitis tended to be more severe in PPI group. As regards effects of PPI on prognosis of two groups, remission rate of radiation pneumonia in PPI group was significantly less than that of the control group. Among 57 cases in PPI group, there were 31 patients applied with PPI ≤ 1DDD and 31 patients applied with PPI > 1DDD. In comparison of the various parameters of patients, 7 days after being applied with different doses of PPI, there were no significant differences between the parameters of radiation pneumonitis. PPIs should be cautiously utilized to avoid the effects of lung cancer radiotherapy-induced radiation pneumonia.

Sulfite hypersensitivity. A critical review

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

The role of lymphocyte proliferation tests in assessing occupational sensitization and disease

PubMed Central

Hines, Stella E.; Pacheco, Karin; Maier, Lisa A.

2018-01-01

Purpose of Review Lymphocyte proliferation testing (LPT) is used in diagnosing occupationally-acquired delayed-type hypersensitivity. It has been used in beryllium-health effects, and it role is expanding in metal allergy. It may find application in diagnosis of other sensitizers. Recent findings Use of the beryllium LPT (BeLPT) in medical surveillance identifies beryllium sensitization at low exposure with chronic beryllium disease (CBD) that leads to physiologic impairment and need for immunosuppressive medications. New studies indicate that both beryllium exposure and genetic variation are associated with increased risk of CBD. Borderline positive BeLPTs warrant inclusion into diagnostic algorithms. Furthermore, use of LPTs to diagnose metal allergy is being proposed in diagnosis of chromium allergy and hypersensitivity to surgical implants. New occupational sensitizers continue to be identified including metalworking fluids, the sterilizing agent ortho-phthalaldehyde and the solvent parachlorobenzotrifluoride. Use of LPT in occupational surveillance to these agents, and other known sensitizers may play expanding roles. Summary Lymphocyte proliferation testing serves a valuable role in diagnosing occupational sensitization, as demonstrated with beryllium-health effects, as cases continue to be found at low exposure levels. The use of LPTs in diagnosing contact allergy is expanding, and new applications may be identified in human and animal studies. PMID:22306552

Incidence of hypersensitivity and anaphylaxis with sugammadex.

PubMed

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

2018-06-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2012-01-01

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

Acute respiratory failure secondary to mesalamine-induced interstitial pneumonitis

PubMed Central

Abraham, Albin; Karakurum, Ali

2013-01-01

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

Acute respiratory failure secondary to mesalamine-induced interstitial pneumonitis.

PubMed

Abraham, Albin; Karakurum, Ali

2013-08-20

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

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

PubMed

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

2013-03-01

Yersinia pestis causes bubonic and pneumonic plague in humans. The pneumonic infection is the most severe and invariably fatal if untreated. Because of its high virulence, ease of delivery and precedent of use in warfare, Y. pestis is considered as a potential bioterror agent. No licensed plague vaccine is currently available in the US. Laboratory research with virulent strains requires appropriate biocontainment (i.e., Biosafety Level 3 (BSL-3) for procedures that generate aerosol/droplets) and secure facilities that comply with federal select agent regulations. To assist in the identification of promising vaccine candidates during the early phases of development, we characterized mouse models of systemic and pneumonic plague infection using the Y. pestis strain EV76, an attenuated human vaccine strain that can be rendered virulent in mice under in vivo iron supplementation. Mice inoculated intranasally or intravenously with Y. pestis EV76 in the presence of iron developed a systemic and pneumonic plague infection that resulted in disease and lethality. Bacteria replicated and severely compromised the spleen, liver and lungs. Susceptibility was age dependent, with younger mice being more vulnerable to pneumonic infection. We used these models of infection to assess the protective capacity of newly developed Salmonella-based plague vaccines. The protective outcome varied depending on the route and dose of infection. Protection was associated with the induction of specific immunological effectors in systemic/mucosal compartments. The models of infection described could serve as safe and practical tools for identifying promising vaccine candidates that warrant further potency evaluation using fully virulent strains in BSL-3 settings. Copyright © 2012 Elsevier Ltd. All rights reserved.

Biodefense-driven murine model of pneumonic melioidosis.

PubMed

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

2003-01-01

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

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

PubMed

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

2009-10-01

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

THE HYPERSENSITIVITY PNEUMONITIS DIAGNOSTIC INDEX: USE OF NON-INVASIVE TESTING TO DIAGNOSE HYPERSENSITIVITY PNEUMONITIS IN METALWORKERS. (R825251)

EPA Science Inventory

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

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

PubMed Central

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

2012-01-01

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

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

PubMed Central

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

2001-01-01

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

Reflux Hypersensitivity: A New Functional Esophageal Disorder

PubMed Central

Yamasaki, Takahisa; Fass, Ronnie

2017-01-01

Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients’ heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity. PMID:28992673

Reflux Hypersensitivity: A New Functional Esophageal Disorder.

PubMed

Yamasaki, Takahisa; Fass, Ronnie

2017-10-30

Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients' heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity.

Hypersensitivity lo local anesthetics.

PubMed

Grzanka, Alicja; Wasilewska, Iwona; Śliwczyńska, Magdalena; Misiołek, Hanna

2016-01-01

Using local anaesthetics in daily practice, particularly by anaesthetists and dentists, is connected with the risk of side effects. Therefore, the observation of side effects, carrying out detailed research (according to the chart proposed in this study) and conducting specialist examinations is of the highest importance. There is a variety of side effects that could occur during local anaesthesia procedures, with the intensity ranging from clinically unimportant to life threatening. Clinicians' major concerns are the appearance of various hypersensitivity reactions, including anaphylaxis. Healthcare providers responsible for the administration of local anaesthetics should be able to detect hypersensitivity reactions to implement appropriate treatment and then choose highly selected diagnostic procedures. The final diagnosis should be based on specific medical history; documentation, including a description of the case and measurement of tryptase activity; skin tests; and provocation trials. Screening tests are not recommended in populations without hypersensitivity to local anaesthestics in their medical history.

Acute hypersensitivity to mannitol: a case report

NASA Astrophysics Data System (ADS)

Siahaan, A. M.; Fithrie, A.

2018-03-01

Mannitol is an osmotic diuretic agent that has been considered a main therapeutic option in cerebral edema for the past several decades. The most common adverse effect reported is acute kidney injury and electrolyte imbalance. Hypersensitivity associated with mannitol is not a usual finding. Here we describe a case of a traumatic brain injury patient who had a hypersensitivity reaction to mannitol. It is the first reported case report about hypersensitivity to Mannitol in Indonesia.

Antigen-specific histamine release in dogs with food hypersensitivity.

PubMed

Ishida, Rinei; Masuda, Kenichi; Sakaguchi, Masahiro; Kurata, Keigo; Ohno, Koichi; Tsujimoto, Hajime

2003-03-01

An in vitro evidence of IgE-mediated hypersensitivity to food allergens was detected by positive results of antigen-specific histamine release in dogs with food hypersensitivity. Eight dogs were diagnosed to have food hypersensitivity based on identification of offending food allergens with food elimination followed by oral food provocation. The percentages of histamine release against the stimulation of offending food allergens in the cases ranged from 2.1% to 70.9%. Six of the 8 cases showed histamine release higher than those of healthy control dogs. Four dogs showed relatively high histamine release at the percentage beyond 10% that was compatible with a positive value of histamine release in humans with food hypersensitivity. These findings would suggest that IgE-mediated hypersensitivity against food allergens could be involved in canine food hypersensitivity.

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

PubMed

Alvarez, M Lucrecia; Cardineau, Guy A

2010-01-01

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

Hypersensitivity Events, Including Potentially Hypersensitivity-Related Skin Events, with Dapagliflozin in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis.

PubMed

Mellander, Annika; Billger, Martin; Johnsson, Eva; Träff, Anna Karin; Yoshida, Shigeru; Johnsson, Kristina

2016-11-01

In patients with type 2 diabetes mellitus (T2DM), dapagliflozin improves glycemic control and has a safety profile typically related to its mechanism of action. Hypersensitivity adverse events (AEs) have been reported in some patients with sodium-glucose cotransporter 2 (SGLT2) inhibitors, including a recent report of dermatological AEs in Japan. We investigated the frequency and characteristics of hypersensitivity AEs, including potentially hypersensitivity-related skin AEs, across 21 phase IIb/III trials of dapagliflozin (N = 5936) versus active or placebo comparators (N = 3403), including the subpopulation of Asian patients (N = 1563). Overall, AEs and serious AEs (SAEs) of hypersensitivity were infrequent and were reported in a similar proportion of patients with dapagliflozin versus active or placebo comparators (AEs: 4.5 vs. 4.3 %; SAEs: 0.2 vs. 0.1 %, respectively). The most common events affected the skin or subcutaneous tissue: rash (dapagliflozin: 1.1 %, comparator: 1.1 %), eczema (0.6, 0.8 %), dermatitis (0.5, 0.4 %), and urticaria (0.5, 0.2 %). Few patients discontinued as a result of hypersensitivity AEs (≤0.2 %). In patients of Asian descent, a lower frequency of hypersensitivity AEs was observed with dapagliflozin versus comparators (2.0 vs. 4.5 %). In the subset of placebo-controlled trials, hypersensitivity AEs were slightly more frequent with dapagliflozin than with placebo across the overall population (4.7 vs. 3.8 %), and less frequent with dapagliflozin in Asian patients (1.5 vs. 5.0 %). The findings of this post hoc analysis indicate that dapagliflozin does not lead to an increased risk of serious hypersensitivity reactions or potentially hypersensitivity-related skin events among patients with T2DM, including Asian patients. Long-term outcome studies and postmarketing surveillance will provide further information on hypersensitivity reactions with SGLT2 inhibitors. CLINICALTRIALS. NCT01042977, NCT01031680, NCT00855166, NCT

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. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Immediate-type hypersensitivity drug reactions.

PubMed

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

2014-07-01

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. © 2013 The British Pharmacological Society.

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

Oral Hypersensitivity Reactions

MedlinePlus

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

Leucovorin-induced hypersensitivity reaction.

PubMed

Damaske, Avni; Ma, Nichole; Williams, Reba

2012-03-01

Leucovorin is a reduced form of folic acid, which has multiple uses.(1) In this case report, it is used in combination with fluorouracil in the treatment of colon cancer. We describe a 53-year-old male, who was started on FOLFOX 6 + bevacizumab who experienced a hypersensitivity reaction to leucovorin. There have been very few cases of leucovorin hypersensitivity reactions reported in the literature. In this case, symptoms include flushing, hives, body pain, headaches, elevated blood pressures, and general discomfort. Although leucovorin reactions are considered rare, one should be aware of the types of reactions that can occur with leucovorin.

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

PubMed

Fritzsch, Joerg; Splettstoesser, Wolf D

2010-09-01

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

Classification and pathophysiology of radiocontrast media hypersensitivity.

PubMed

Brockow, Knut; Ring, Johannes

2010-01-01

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

Drug metabolism and hypersensitivity reactions to drugs.

PubMed

Agúndez, José A G; Mayorga, Cristobalina; García-Martin, Elena

2015-08-01

The aim of the present review was to discuss recent advances supporting a role of drug metabolism, and particularly of the generation of reactive metabolites, in hypersensitivity reactions to drugs. The development of novel mass-spectrometry procedures has allowed the identification of reactive metabolites from drugs known to be involved in hypersensitivity reactions, including amoxicillin and nonsteroidal antiinflammatory drugs such as aspirin, diclofenac or metamizole. Recent studies demonstrated that reactive metabolites may efficiently bind plasma proteins, thus suggesting that drug metabolites, rather than - or in addition to - parent drugs, may elicit an immune response. As drug metabolic profiles are often determined by variability in the genes coding for drug-metabolizing enzymes, it is conceivable that an altered drug metabolism may predispose to the generation of reactive drug metabolites and hence to hypersensitivity reactions. These findings support the potential for the use of pharmacogenomics tests in hypersensitivity (type B) adverse reactions, in addition to the well known utility of these tests in type A adverse reactions. Growing evidence supports a link between genetically determined drug metabolism, altered metabolic profiles, generation of highly reactive metabolites and haptenization. Additional research is required to developing robust biomarkers for drug-induced hypersensitivity reactions.

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

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

PubMed

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

2014-10-01

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

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

Mycobacterial Aerosols and Respiratory Disease

PubMed Central

2003-01-01

Environmental opportunistic mycobacteria, including Mycobacterium avium, M. terrae, and the new species M. immunogenum, have been implicated in outbreaks of hypersensitivity pneumonitis or respiratory problems in a wide variety of settings. One common feature of the outbreaks has been exposure to aerosols. Aerosols have been generated from metalworking fluid during machining and grinding operations as well as from indoor swimming pools, hot tubs, and water-damaged buildings. Environmental opportunistic mycobacteria are present in drinking water, resistant to disinfection, able to provoke inflammatory reactions, and readily aerosolized. In all outbreaks, the water sources of the aerosols were disinfected. Disinfection may select for the predominance and growth of mycobacteria. Therefore, mycobacteria may be responsible, in part, for many outbreaks of hypersensitivity pneumonitis and other respiratory problems in the workplace and home. PMID:12890314

Mycobacterial aerosols and respiratory disease.

PubMed

Falkinham, Joseph O

2003-07-01

Environmental opportunistic mycobacteria, including Mycobacterium avium, M. terrae, and the new species M. immunogenum, have been implicated in outbreaks of hypersensitivity pneumonitis or respiratory problems in a wide variety of settings. One common feature of the outbreaks has been exposure to aerosols. Aerosols have been generated from metalworking fluid during machining and grinding operations as well as from indoor swimming pools, hot tubs, and water-damaged buildings. Environmental opportunistic mycobacteria are present in drinking water, resistant to disinfection, able to provoke inflammatory reactions, and readily aerosolized. In all outbreaks, the water sources of the aerosols were disinfected. Disinfection may select for the predominance and growth of mycobacteria. Therefore, mycobacteria may be responsible, in part, for many outbreaks of hypersensitivity pneumonitis and other respiratory problems in the workplace and home.

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

PubMed Central

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

2018-01-01

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

[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.

The canine model of dietary hypersensitivity.

PubMed

Day, Michael J

2005-11-01

IgE-mediated dietary hypersensitivity affects approximately 1% of the canine population. There are no breed associations and < or =50% of the patients are aged <1 year at presentation. The most common causative allergens are beef, chicken, milk, eggs, maize, wheat and soyabean. Affected dogs generally display cutaneous disease and 10-15% of the patients may have concurrent alimentary involvement. Diagnosis is currently based on dietary restriction followed by provocation. Procedures for the detection of serum allergen-specific IgE and IgG antibodies are widely available, but these tests correlate poorly with clinical presentation and dietary testing. Recent studies have demonstrated the allergen specificity of IgE antibodies by immunoblotting and have described blood lymphocyte proliferative responses to food allergens. In addition to investigations of spontaneously-arising dietary hypersensitivity, it has also proved possible to study this disorder experimentally. Small colonies of dogs sensitive to particular dietary proteins have been used to study clinical and serological responses to allergen challenge. Hypersensitivity has been experimentally induced in dogs of an atopic phenotype by repeated subcutaneous injection of alum-adjuvanted dietary allergen during neonatal life. These models have been used to trial a range of modified protein or hydrolysate diets. The dog provides a unique large-animal model for investigation of the immunopathogenesis of human dietary hypersensitivity. The dog is closely related genetically to man and shares environmental disease triggers with man. Spontaneously arising canine dietary hypersensitivity is a good clinical mimic of the human disease, and ability to therapeutically manipulate this adverse response in the dog might lead to benefits for human patients.

Spatially distinct neutrophil responses within the inflammatory lesions of pneumonic plague.

PubMed

Stasulli, Nikolas M; Eichelberger, Kara R; Price, Paul A; Pechous, Roger D; Montgomery, Stephanie A; Parker, Joel S; Goldman, William E

2015-10-13

During pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence are poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and transcriptome sequencing (RNA-seq) analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are downregulated in the center of lung lesions compared to the periphery. Probing for the bacterial factor(s) important for the alteration in neutrophil survival, we show both in vitro and in vivo that Y. pestis increases neutrophil survival in a manner that is dependent on the type III secretion system effector YopM. This research explores the complexity of spatially distinct host-microbe interactions and emphasizes the importance of cell relevance in assays in order to fully understand Y. pestis virulence. Yersinia pestis is a high-priority pathogen and continues to cause outbreaks worldwide. The ability of Y. pestis to be transmitted via respiratory droplets and its history of weaponization has led to its classification as a select agent most likely to be used as a biological weapon. Unrestricted bacterial growth during the initial preinflammatory phase primes patients to be infectious once disease symptoms begin in the proinflammatory phase, and the rapid disease progression can lead to death before Y. pestis infection can be diagnosed and treated. Using in vivo analyses and focusing on relevant cell types during pneumonic plague infection, we can identify host pathways that may be manipulated to extend the treatment window for pneumonic plague patients. Copyright © 2015 Stasulli et al.

Cardiac Iodine-123-Meta-Iodo-Benzylguanidine Uptake in Carotid Sinus Hypersensitivity

PubMed Central

Tan, Maw Pin; Murray, Alan; Hawkins, Terry; Chadwick, Thomas J.; Kerr, Simon R. J.; Parry, Steve W.

2015-01-01

Background Carotid sinus syndrome is the association of carotid sinus hypersensitivity with syncope, unexplained falls and drop attacks in generally older people. We evaluated cardiac sympathetic innervation in this disorder in individuals with carotid sinus syndrome, asymptomatic carotid sinus hypersensitivity and controls without carotid sinus hypersensitivity. Methods Consecutive patients diagnosed with carotid sinus syndrome at a specialist falls and syncope unit were recruited. Asymptomatic carotid sinus hypersensitivity and non-carotid sinus hypersensitivity control participants recruited from a community-dwelling cohort. Cardiac sympathetic innervation was determined using Iodine-123-metaiodobenzylguanidine (123-I-MIBG) scanning. Heart to mediastinal uptake ratio (H:M) were determined for early and late uptake on planar scintigraphy at 20 minutes and 3 hours following intravenous injection of 123-I-MIBG. Results Forty-two subjects: carotid sinus syndrome (n = 21), asymptomatic carotid sinus hypersensitivity (n = 12) and no carotid sinus hypersensitivity (n = 9) were included. Compared to the non- carotid sinus hypersensitivity control group, the carotid sinus syndrome group had significantly higher early H:M (estimated mean difference, B = 0.40; 95% confidence interval, CI = 0.13 to 0.67, p = 0.005) and late H:M (B = 0.32; 95%CI = 0.03 to 0.62, p = 0.032). There was, however, no significant difference in early H:M (p = 0.326) or late H:M (p = 0.351) between the asymptomatic carotid sinus hypersensitivity group and non- carotid sinus hypersensitivity controls. Conclusions Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome but not those with asymptomatic carotid sinus hypersensitivity. Blood pressure and heart rate measurements alone may therefore represent an over simplification in the assessment for carotid sinus syndrome and the relative increase in cardiac sympathetic innervation

Cardiac Iodine-123-Meta-Iodo-Benzylguanidine Uptake in Carotid Sinus Hypersensitivity.

PubMed

Tan, Maw Pin; Murray, Alan; Hawkins, Terry; Chadwick, Thomas J; Kerr, Simon R J; Parry, Steve W

2015-01-01

Carotid sinus syndrome is the association of carotid sinus hypersensitivity with syncope, unexplained falls and drop attacks in generally older people. We evaluated cardiac sympathetic innervation in this disorder in individuals with carotid sinus syndrome, asymptomatic carotid sinus hypersensitivity and controls without carotid sinus hypersensitivity. Consecutive patients diagnosed with carotid sinus syndrome at a specialist falls and syncope unit were recruited. Asymptomatic carotid sinus hypersensitivity and non-carotid sinus hypersensitivity control participants recruited from a community-dwelling cohort. Cardiac sympathetic innervation was determined using Iodine-123-metaiodobenzylguanidine (123-I-MIBG) scanning. Heart to mediastinal uptake ratio (H:M) were determined for early and late uptake on planar scintigraphy at 20 minutes and 3 hours following intravenous injection of 123-I-MIBG. Forty-two subjects: carotid sinus syndrome (n = 21), asymptomatic carotid sinus hypersensitivity (n = 12) and no carotid sinus hypersensitivity (n = 9) were included. Compared to the non- carotid sinus hypersensitivity control group, the carotid sinus syndrome group had significantly higher early H:M (estimated mean difference, B = 0.40; 95% confidence interval, CI = 0.13 to 0.67, p = 0.005) and late H:M (B = 0.32; 95%CI = 0.03 to 0.62, p = 0.032). There was, however, no significant difference in early H:M (p = 0.326) or late H:M (p = 0.351) between the asymptomatic carotid sinus hypersensitivity group and non- carotid sinus hypersensitivity controls. Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome but not those with asymptomatic carotid sinus hypersensitivity. Blood pressure and heart rate measurements alone may therefore represent an over simplification in the assessment for carotid sinus syndrome and the relative increase in cardiac sympathetic innervation provides additional clues to

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

PubMed Central

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

2010-01-01

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

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

PubMed

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

2010-05-01

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

Desensitization for Drug Hypersensitivity to Chemotherapy and Monoclonal Antibodies.

PubMed

Bonamichi-Santos, Rafael; Castells, Mariana

2016-01-01

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

Evaluation of dose response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy

NASA Astrophysics Data System (ADS)

Tsougos, Ioannis; Mavroidis, Panayiotis; Rajala, Juha; Theodorou, Kyriaki; Järvenpää, Ritva; Pitkänen, Maunu A.; Holli, Kaija; Ojala, Antti T.; Lind, Bengt K.; Hyödynmaa, Simo; Kappas, Constantin

2005-08-01

The purpose of this work is to evaluate the predictive strength of the relative seriality, parallel and LKB normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis, in a large group of patients following breast cancer radiotherapy, and furthermore, to illustrate statistical methods for examining whether certain published radiobiological parameters are compatible with a clinical treatment methodology and patient group characteristics. The study is based on 150 consecutive patients who received radiation therapy for breast cancer. For each patient, the 3D dose distribution delivered to lung and the clinical treatment outcome were available. Clinical symptoms and radiological findings, along with a patient questionnaire, were used to assess the manifestation of radiation-induced complications. Using this material, different methods of estimating the likelihood of radiation effects were evaluated. This was attempted by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Additionally, the need for an update of the criteria that are being used in the current clinical practice was also examined. The patient material was selected without any conscious bias regarding the radiotherapy treatment technique used. The treatment data of each patient were applied to the relative seriality, LKB and parallel NTCP models, using published parameter sets. Of the 150 patients, 15 experienced radiation-induced pneumonitis (grade 2) according to the radiation pneumonitis scoring criteria used. Of the NTCP models examined, the relative seriality model was able to predict the incidence of radiation pneumonitis with acceptable accuracy, although radiation pneumonitis was developed by only a few patients. In the case of modern breast radiotherapy, radiobiological modelling appears to be very sensitive to model and parameter selection giving clinically

Decreased Risk of Radiation Pneumonitis With Incidental Concurrent Use of Angiotensin-Converting Enzyme Inhibitors and Thoracic Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kharofa, Jordan; Cohen, Eric P.; Tomic, Rade

2012-09-01

Purpose: Angiotensin-converting enzyme (ACE) inhibitors have been shown to mitigate radiation-induced lung injury in preclinical models. The aim of this study was to evaluate whether ACE inhibitors decrease the risk of radiation pneumonitis in lung cancer patients receiving thoracic irradiation. Methods and Materials: Patients with Stage I through III small-cell and non-small-cell lung cancer treated definitively with radiation from 2004-2009 at the Clement J. Zablocki Veterans Affairs Medical Center were retrospectively reviewed. Acute pulmonary toxicity was quantified within 6 months of completion of treatment according to the Common Terminology Criteria for Adverse Events version 4. The use of ACE inhibitors,more » nonsteroidal anti-inflammatory drugs, inhaled glucocorticosteroids, statins, and angiotensin receptor blockers; dose-volume histogram parameters; and patient factors were assessed for association with Grade 2 or higher pneumonitis. Results: A total of 162 patients met the criteria for inclusion. The majority of patients had Stage III disease (64%) and received concurrent chemotherapy (61%). Sixty-two patients were identified as ACE inhibitor users (38%). All patients had acceptable radiation plans based on dose-volume histogram constraints (V20 [volume of lung receiving at least 20 Gy] {<=}37% and mean lung dose {<=}20 Gy) with the exception of 2 patients who did not meet both criteria. Grade 2 or higher pulmonary toxicity occurred in 12 patients (7.4%). The rate of Grade 2 or higher pneumonitis was lower in ACE inhibitor users vs. nonusers (2% vs. 11%, p = 0.032). Rates of Grade 2 or higher pneumonitis were significantly increased in patients aged greater than 70 years (16% vs. 2%, p = 0.005) or in whom V5 (volume of lung receiving at least 5 Gy) was 50% or greater (13% vs. 4%, p = 0.04). V10 (volume of lung receiving at least 10 Gy), V20, V30 (volume of lung receiving at least 30 Gy), and mean lung dose were not independently associated with Grade

Occupational protein contact dermatitis.

PubMed

Barbaud, Annick; Poreaux, Claire; Penven, Emmanuelle; Waton, Julie

2015-01-01

Occupational contact dermatitis is generally caused by haptens but can also be induced by proteins causing mainly immunological contact urticaria (ICU); chronic hand eczema in the context of protein contact dermatitis (PCD). In a monocentric retrospective study, from our database, only 31 (0.41%) of patients with contact dermatitis had positive skin tests with proteins: 22 had occupational PCD, 3 had non-occupational PCD, 5 occupational ICU and 1 cook had a neutrophilic fixed food eruption (NFFE) due to fish. From these results and analysis of literature, the characteristics of PCD can be summarized as follows. It is a chronic eczematous dermatitis, possibly exacerbated by work, suggestive if associated with inflammatory perionyxix and immediate erythema with pruritis, to be investigated when the patient resumes work after a period of interruption. Prick tests with the suspected protein-containing material are essential, as patch tests have negative results. In case of multisensitisation revealed by prick tests, it is advisable to analyse IgE against recombinant allergens. A history of atopy, found in 56 to 68% of the patients, has to be checked for. Most of the cases are observed among food-handlers but PCD can also be due to non-edible plants, latex, hydrolysed proteins or animal proteins. Occupational exposure to proteins can thus lead to the development of ICU. Reflecting hypersensitivity to very low concentrations of allergens, investigating ICU therefore requires caution and prick tests should be performed with a diluted form of the causative protein-containing product. Causes are food, especially fruit peel, non-edible plants, cosmetic products, latex, animals.

Neuropeptide Y stimulation as primary target for preventive measures of maladaptative cardiovascular reactions in occupational chronic stress exposure.

PubMed

Ciumaşu-Rîmbu, Mălina; Popa, Livia; Vulpoi, Carmen

2012-01-01

Chronic stress may produce a decrease in central NPY expression and subjects exposed to it may prove hypersensitivity to a novel stressor with dysfunctions in the NPY system and cardiovascular maladaptation to stress, even hypertension. Upregulation of NPY expression may contribute to successful behavioral adaptation to stress by reducing cardiovascular tone and suppressing anxious behaviors. Adaptogens, a new class of metabolic regulators stimulate NPY expression and release. The aim of this study is to increase tolerance and adaptation to stress of hypersensitive to novel stressor, occupational chronic stress exposed subjects with cardiovascular maladaptation to mild new stressor using adaptogens as part of prevention protocol. 40 military personnel with known cardiostressor reactional mode and occupational chronic stress exposure were exposed to mild novel stressor: occupational medicine routine evaluation and clinically assessed for maladaptative cardiovascular response prior and before application of 30 day prevention protocol. Employees were randomly split in two groups, one receiving standard prevention protocol (lifestyle counseling) plus adaptogens in multiple dose administration, twice daily and the other receiving only standard prevention protocol. We found significant statistic differences in all cardiovascular parameters in adaptogen group and only in diastolic blood pressure in control group. Adaptogens could be an important factor in successful prevention protocols of chronic occupational stress dysfunctions involving NPY systems.

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.

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

PubMed Central

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

2011-01-01

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

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

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

[Food hypersensitivity dermatitis in the dog: diagnostic possibilities].

PubMed

Wilhelm, S; Favrot, C

2005-04-01

Dogs with food hypersensitivity usually develop chronic pruritic dermatoses virtually indistinguishable from atopic dermatitis. These reactions are often called food allergy but the pathogenesis is poorly characterized. Several studies have addressed the incidence of canine adverse reactions to food but the outcomes were conflicting. The gold standard for the diagnosis of such a condition is the restricted dietary trial and the subsequent provocation challenge. Some attempts have been made to develop serological tests but none of these tests accurately predicted canine food sensitivity. The aim of the present study was to determine the incidence of food hypersensitivity dermatitis and to evaluate a newly developed serological test for the diagnosis of food allergy in dogs. Only 9% of 55 dogs with dermatological signs compatible with food hypersensitivity or atopic dermatitis have been diagnosed as food hypersensitive dogs. The repeatability of the serological test has shown to be insufficient.

Entomologic evaluation of insect hypersensitivity in horses.

PubMed

Greiner, E C

1995-04-01

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

Managing hypersensitivity to asparaginase in pediatrics, adolescents, and young adults.

PubMed

Shinnick, Sara E; Browning, Mary L; Koontz, Susannah E

2013-01-01

Hypersensitivity reactions to chemotherapeutic drugs have been documented for numerous cancer therapies. Clinical hypersensitivity to Escherichia coli asparaginase has been reported to range from 0% to 75%. Throughout the United States, nurses assume frontline responsibility for the assessment of asparaginase-related hypersensitivity reactions. It is essential that nurses educate themselves on the signs and symptoms of asparaginase-related hypersensitivity reactions as well as current supportive care approaches. The purpose of this review is to summarize acute lymphoblastic leukemia and the role of asparaginase and the pathology of allergic reactions. We will also update nurses on the differences in asparaginase preparations including dosing, half-life, rates of hypersensitivity, and routes of administration. A summary of current management and supportive care strategies will be provided as will a discussion of the relationship between allergy, antibodies, and asparaginase activity.

Practical Management of Antibiotic Hypersensitivity in 2017.

PubMed

Macy, Eric; Romano, Antonino; Khan, David

Antibiotics are the most common class of medications that individuals report allergy or intolerance to. Adverse reactions are reported at a predictable rate with all antibiotic use that vary by antibiotic. Antibiotic allergy incidence rates are sex dependent, higher in females than in males. Most of these events are not reproducible or immunologically mediated. Antibiotic allergy prevalence increases with increasing age and is more common in hospitalized populations and in populations that use more antibiotics. Determining potential mechanisms for the observed symptoms of the adverse reactions is the starting point for effective management of antibiotic hypersensitivity. Skin testing and direct challenges are the primary tools used to determine acute tolerance in 2017. Commercially available in vitro testing is not currently clinically useful in determining antibiotic hypersensitivity, with rare exceptions. Desensitization can be used when acute-onset immunologically mediated hypersensitivity is confirmed to safely administer a needed antibiotic. Desensitization is not possible when clinically significant T-cell-mediated delayed-type hypersensitivity is present. Effective management of antibiotic allergy is an important part of a comprehensive antibiotic stewardship program. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Cat-transmitted fatal pneumonic plague in a person who traveled from Colorado to Arizona.

PubMed

Doll, J M; Zeitz, P S; Ettestad, P; Bucholtz, A L; Davis, T; Gage, K

1994-07-01

Plague, primarily a disease of rodents and their infected fleas, is fatal in 50% of infected humans if untreated. In the United States, human cases have been concentrated in the southwest. The most common modes of plague transmission are through flea bites or through contact with infected blood or tissues; however, primary pneumonic plague acquired from cats has become increasingly recognized. We report on the case investigation of a patient, presumably exposed to a plague-infected cat in Colorado, who presented with gastrointestinal symptoms, and subsequently died of primary pneumonic plague. Public health officials should be vigilant for plague activity in rodent populations, veterinarians should suspect feline plague in ill or deceased cats, and physicians should have a high index of suspicion for plague in any person who has traveled to plague enzootic areas.

Corticosteroid hypersensitivity studies in a skin allergy clinic.

PubMed

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

2015-12-01

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

An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity

PubMed Central

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

2018-01-01

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

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. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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

PubMed

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

2013-12-01

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

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

PubMed

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

2017-01-01

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

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

Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies

PubMed Central

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

2017-01-01

We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease (P < 0.001, Kruskal-Wallis test), serous and mixed histological types (P = 0.003, Kruskal-Wallis test), malignant ascites (P = 0.009, chi-square test), and history of other drug allergy (P < 0.001, chi-square test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P < 0.001, independent sample t-test) and dose (6,816 vs. 3,844 mg, P < 0.001, independent sample t-test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications. PMID:29163180

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

PubMed

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

2017-01-01

We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease ( P < 0.001, Kruskal-Wallis test), serous and mixed histological types ( P = 0.003, Kruskal-Wallis test), malignant ascites ( P = 0.009, chi-square test), and history of other drug allergy ( P < 0.001, chi-square test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P < 0.001, independent sample t -test) and dose (6,816 vs. 3,844 mg, P < 0.001, independent sample t -test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.

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

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

Management of trichomonas vaginalis in women with suspected metronidazole hypersensitivity.

PubMed

Helms, Donna J; Mosure, Debra J; Secor, W Evan; Workowski, Kimberly A

2008-04-01

Standard treatment for Trichomonas vaginalis is metronidazole or tinidazole. Hypersensitivity to these drugs has been documented but is poorly understood. Desensitization is an option described in limited reports of women with hypersensitivity to nitroimidazoles. The purpose of this analysis is to improve documentation of management for trichomonas infections among women with metronidazole hypersensitivity. Clinicians who consulted Centers for Disease Control and Prevention concerning patients with suspected hypersensitivity to metronidazole were provided with treatment options and asked to report outcomes. From September 2003-September 2006, complete information was obtained for 59 women. The most common reactions were urticaria (47%) and facial edema (11%). Fifteen of these women (25.4%) were treated with metronidazole desensitization and all had eradication of their infection. Seventeen women (28.8%) were treated with alternative intravaginal drugs, which were less successful; 5 of 17 infections (29.4%) were eradicated. Metronidazole desensitization was effective in the management of women with nitroimidazole hypersensitivity.

Bird fanciers lung in mushroom workers.

PubMed

Hayes, J; Barrett, M

2015-04-01

Hypersensitivity pneumonitis has been described in mushrooms workers caused by exposure to mushroom or fungal spores in the compost used to grow mushrooms. We describe two mushroom workers who developed hypersensitivity pneumonitis due to exposure to avian proteins found in poultry manure which was used in producing mushroom compost. Both workers were employed in the compost production area. Both presented with typical features of HP. Both workers had negative serological and precipitin studies to Apergillus fumigatus, Saccarhopolyspora rectivirgula and thermophilic actinomycetes but had positive responses to poultry antibodies. Neither was exposed to mushroom spores. Both workers required initial therapy with corticosteroids. Relocation with avoidance of further exposure resulted in complete cure in one worker and change in work practice with the use of personal protections equipment resulted in the second workerclinical stabilisation. These are the first reported cases of bird fanciers lung in mushroom workers.

HLA-B*1301 as a Biomarker for Genetic Susceptibility to Hypersensitivity Dermatitis Induced by Trichloroethylene among Workers in China

PubMed Central

Li, Haishan; Dai, Yufei; Huang, Hanlin; Li, Laiyu; Leng, Shuguang; Cheng, Juan; Niu, Yong; Duan, Huawei; Liu, Qingjun; Zhang, Xing; Huang, Xianqing; Xie, Jinxin; Feng, Zhiming; Wang, Juncai; He, Jiaxi; Zheng, Yuxin

2007-01-01

Background Trichloroethylene (TCE) is used extensively as an industrial solvent and has been recognized as one of the major environmental pollutants. To date, > 200 cases of TCE-induced hypersensitivity dermatitis among exposed workers have been reported worldwide, and TCE exposure has become one of the critical occupational health issues in Asia. Objectives The study aimed to identify genetic susceptible biomarkers associated with the TCE-induced hypersensitivity dermatitis in genes located in the human leukocyte antigen (HLA) region. Methods From 1998 to 2006, 121 cases with TCE-induced hypersensitivity dermatitis and 142 tolerant controls were recruited into the population-based case–control study. We determined HLA alleles B, DRB1, DQA1, and DQB1, by sequence-based typing. p-Values were corrected for comparisons of multiple HLA alleles. In addition, we compared and analyzed the structure character of amino acid residues of HLA molecules found in participants. Results We obtained complete genotyping data of 113 cases and 142 controls. The allele HLA-B*1301 was present in 83 (73.5%) of 113 patients compared with 13 (9.2%) of 142 tolerant workers (odds ratio = 27.5; 95% confidence interval, 13.5–55.7; corrected p = 1.48 × 10−21). In addition, the HLA-B*44 alleles were present in 6.2% (7/113) of patients, but were absent in TCE-tolerant workers. Residue 95 shared by HLA-B*1301 and HLA-B*44 molecules formed a different pocket F than other residues. Conclusions The allele HLA-B*1301 is strongly associated with TCE-induced hypersensitivity dermatitis among exposed workers and might be used as a biomarker to predict high risk individuals to TCE. PMID:18007983

Pneumonitis: a serious adverse effect of PD-L1 inhibitors including pembrolizumab.

PubMed

Rickard, Frances; Hyams, Catherine; Low, Andrew T

2018-05-07

A 70-year-old man presented with breathlessness, cough and fever while receiving pembrolizumab for melanoma. A CT pulmonary angiogram demonstrated small bilateral upper lobe segmental pulmonary emboli with patchy ground-glass opacities and basal perilobular consolidation, in keeping with organising pneumonia. He was treated for community-acquired pneumonia and pulmonary emboli but rapidly deteriorated, with increasing hypoxia and dyspnoea. He was admitted to the intensive care unit for support with continuous positive airway pressure and high flow nasal oxygen. His clinical condition improved once he received high-dose intravenous methylprednisolone to treat pneumonitis. His treatment was continued with a weaning course of high-dose oral steroids, and he was discharged with a persistent oxygen requirement. The patient maintained a requirement for high doses of oral steroids and continued to deteriorate. He was referred to palliative care for symptom management and died a month following hospital discharge, as a result of pneumonitis due to pembrolizumab. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Association of HLA genotypes with phenobarbital hypersensitivity in children.

PubMed

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

2016-10-01

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

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

PubMed

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

2017-11-01

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

Self-report prevalence and associated factors to drug hypersensitivity in Mexican young adults.

PubMed

Bedolla-Barajas, Martín; Puente-Fernández, Cecilia; Flores-Merino, Miriam V; Morales-Romero, Jaime; Domínguez-García, Ma Victoria

2017-07-01

Drug hypersensitivity is defined as any unfavorable reaction that occurs after the administration of any drug. It may or may not be mediated by the involvement of the immune system. Epidemiological data related to drug hypersensitivity reactions in our country are scarce. To determine the prevalence of drug hypersensitivity in a group of young adults, as well as to identify associated factors. A structured questionnaire was applied to young people aged 18 to 25 years. The instrument was oriented to identify reactions of drug hypersensitivity, as well as the most prevalent drugs involved. In addition, a personal and family history of atopic diseases was included. Analysis for associations between variables was been done through logistic regression. The prevalence of drug hypersensitivity reactions was 12% (144 of 1,200). The antibiotics were the agents most related to hypersensitivity reactions (9.8%) followed by nonsteroidal anti-inflammatory drugs (1.6%). Factors associated with drug hypersensitivity were a personal history of asthma, odds ratio (OR) 3.15 (95% confidence interval [CI], 1.44-6.91), maternal and paternal history of drug hypersensitivity, OR 2.33 (95% CI, 1.21-4.48) and OR 3.11 (95% CI, 1.22-7.92), respectively. The results of this research show that drug hypersensitivity in young adults is a highly prevalent event and it is associated with personal history of asthma and history of drug hypersensitivity in parents.

Using patient data similarities to predict radiation pneumonitis via a self-organizing map

NASA Astrophysics Data System (ADS)

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

2008-01-01

This work investigates the use of the self-organizing map (SOM) technique for predicting lung radiation pneumonitis (RP) risk. SOM is an effective method for projecting and visualizing high-dimensional data in a low-dimensional space (map). By projecting patients with similar data (dose and non-dose factors) onto the same region of the map, commonalities in their outcomes can be visualized and categorized. Once built, the SOM may be used to predict pneumonitis risk by identifying the region of the map that is most similar to a patient's characteristics. Two SOM models were developed from a database of 219 lung cancer patients treated with radiation therapy (34 clinically diagnosed with Grade 2+ pneumonitis). The models were: SOMall built from all dose and non-dose factors and, for comparison, SOMdose built from dose factors alone. Both models were tested using ten-fold cross validation and Receiver Operating Characteristics (ROC) analysis. Models SOMall and SOMdose yielded ten-fold cross-validated ROC areas of 0.73 (sensitivity/specificity = 71%/68%) and 0.67 (sensitivity/specificity = 63%/66%), respectively. The significant difference between the cross-validated ROC areas of these two models (p < 0.05) implies that non-dose features add important information toward predicting RP risk. Among the input features selected by model SOMall, the two with highest impact for increasing RP risk were: (a) higher mean lung dose and (b) chemotherapy prior to radiation therapy. The SOM model developed here may not be extrapolated to treatment techniques outside that used in our database, such as several-field lung intensity modulated radiation therapy or gated radiation therapy.

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

PubMed

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

2015-09-01

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. This study proposed to evaluate the desensitizing effect of the oxalic acid agent on pain caused by dentin hypersensitivity during ultrasonic scaling. 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. 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. 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.

Diagnostic testing of dogs for food hypersensitivity.

PubMed

Jeffers, J G; Shanley, K J; Meyer, E K

1991-01-15

Thirteen food-allergic dogs were studied to evaluate the efficacy of feeding a commercially available egg and rice diet, intradermal skin testing, and serologic testing by ELISA for diagnosing and/or characterizing food hypersensitivity. Feeding of a home-cooked whole lamb meat and rice diet for 3 weeks, followed by challenge with each dog's regular diet, served as the standard for diagnosing food hypersensitivity. Each dog underwent provocative testing with 6 individual ingredients to determine as many of its dietary allergens as possible. Prior to skin testing and serologic testing by ELISA, most dogs had been recently exposed to the offending diet and subsequently manifested clinical signs of allergy. All dogs that tolerated the aforementioned commercial diet were exposed to it for at least 7 weeks; 84.6% of food-hypersensitive dogs ate the commercial diet with impunity. Of the 2 reactors to the commercial diet, only 1 became pruritic in response to provocation testing with chicken eggs. Low sensitivity and high specificity were found for skin testing and the ELISA, indicating a lack of true- and false-positive reactions. Neither the positive nor negative predictive values adequately predicted positive and negative reactions, respectively, for either test. On the basis of these results, the commercial diet, skin testing, and anti-IgE ELISA cannot replace an owner-prepared food elimination diet for food hypersensitivity testing in dogs.

Life threatening acute pneumonitis during low dose methotrexate treatment for rheumatoid arthritis: a case report and review of the literature.

PubMed Central

Ridley, M G; Wolfe, C S; Mathews, J A

1988-01-01

A patient is described with definite rheumatoid arthritis (RA) who developed life threatening acute pneumonitis after receiving a total dose of only 12.5 mg methotrexate (MTX). This complication has been previously described, but this is probably the lowest reported dose before development of pneumonitis in a patient with RA. The possible significance of this case is discussed in the light of recent reports suggesting an increased susceptibility of patients with RA to the pulmonary toxicity of MTX. Images PMID:3052323

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

PubMed

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

2016-11-11

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

Metal hypersensitivity after knee arthroplasty: fact or fiction?

PubMed

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

2017-06-07

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

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

Outpatient desensitization in selected patients with platinum hypersensitivity reactions.

PubMed

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

2017-06-01

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

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

Current Epidemiologic Trends of the Nontuberculous Mycobacteria (NTM).

PubMed

Falkinham, Joseph O

2016-06-01

The nontuberculous mycobacteria (NTM) are waterborne opportunistic pathogens of humans. They are normal inhabitants of premise plumbing, found, for example, in household and hospital shower heads, water taps, aerators, and hot tubs. The hydrophobic NTM are readily aerosolized, and pulmonary infections and hypersensitivity pneumonitis have been traced to the presence of NTM in shower heads. Hypersensitivity pneumonitis in automotive workers was traced to the presence of NTM in metal recovery fluid used in grinding operations. Recently, NTM bacteremia in heart transplant patients has been traced to the presence of NTM in water reservoirs of instruments employed in operating rooms to heat and cool patient blood during periods of mechanical circulation. Although NTM are difficult to eradicate from premise plumbing as a consequence of their disinfectant-resistance and formation of biofilms, measures such as reduction of turbidity and reduction in carbon and nitrogen for growth and the installation of microbiological filters can reduce exposure of NTM to susceptible individuals.

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

PubMed

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

2014-06-01

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

Deletion of Braun Lipoprotein and Plasminogen-Activating Protease-Encoding Genes Attenuates Yersinia pestis in Mouse Models of Bubonic and Pneumonic Plague

PubMed Central

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

2014-01-01

Currently, there is no FDA-approved vaccine against Yersinia pestis, the causative agent of bubonic and pneumonic plague. Since both humoral immunity and cell-mediated immunity are essential in providing the host with protection against plague, we developed a live-attenuated vaccine strain by deleting the Braun lipoprotein (lpp) and plasminogen-activating protease (pla) genes from Y. pestis CO92. The Δlpp Δpla double isogenic mutant was highly attenuated in evoking both bubonic and pneumonic plague in a mouse model. Further, animals immunized with the mutant by either the intranasal or the subcutaneous route were significantly protected from developing subsequent pneumonic plague. In mice, the mutant poorly disseminated to peripheral organs and the production of proinflammatory cytokines concurrently decreased. Histopathologically, reduced damage to the lungs and livers of mice infected with the Δlpp Δpla double mutant compared to the level of damage in wild-type (WT) CO92-challenged animals was observed. The Δlpp Δpla mutant-immunized mice elicited a humoral immune response to the WT bacterium, as well as to CO92-specific antigens. Moreover, T cells from mutant-immunized animals exhibited significantly higher proliferative responses, when stimulated ex vivo with heat-killed WT CO92 antigens, than mice immunized with the same sublethal dose of WT CO92. Likewise, T cells from the mutant-immunized mice produced more gamma interferon (IFN-γ) and interleukin-4. These animals had an increasing number of tumor necrosis factor alpha (TNF-α)-producing CD4+ and CD8+ T cells than WT CO92-infected mice. These data emphasize the role of TNF-α and IFN-γ in protecting mice against pneumonic plague. Overall, our studies provide evidence that deletion of the lpp and pla genes acts synergistically in protecting animals against pneumonic plague, and we have demonstrated an immunological basis for this protection. PMID:24686064

Chronic occupational stress exposure may increase the vulnerability to acoustic trauma in military professionals.

PubMed

Mălina, Ciumaşu-Rimbu

2015-01-01

Today little is known about the connection between chronic stress exposure and hearing loss. These effects cannot be explained by differences in HPA axis response but recent studies saying that chronic stress induced limbic system alterations spread to nonlimbic areas affecting auditory system might be the key. On the other hand we know that subjects exposed to chronic stress may prove hypersensitivity to novel stressors. The aim of this study is to confirm that occupational chronic stress (OCS) exposure determines vulnerability to acoustic trauma and to establish a method to identify individuals at risk prior to their exposure to high intensity acoustic stimulus. 60 military personnel with known acoustic trauma injury evidentiated through audiograms and occupational chronic stress exposure quantified through validated questionnaires were exposed to mild novel stressor: occupational medicine evaluation and clinically assessed for maladaptive cardiovascular response (MCVR). Employees were split in two groups, group 1 (MCVR) and group 2 (non MCVR). We found positive correlation between level of perceived OCS and level of hearing loss on entire group and between groups with values of parameters significantly higher in group 1. Subjects exposed to OCS with hypersensitivity to novel stressor evidentiated through maladaptive cardiovascular stress response may be more vulnerable to high intensity acoustic stimulus and consequently acoustic trauma. Establishing methods and biomarkers that help us indentify individuals at risk of developing acoustic trauma might decrease the high burden of hearing loss.

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. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

[Hypersensitivity to dacarbazine in patients with metastatic malignant melanoma].

PubMed

Levy, A; Guitera, P; Kerob, D; Ollivaud, L; Archimbaud, A; Dubertret, L; Basset-Seguin, N

2006-02-01

Dacarbazine (DTIC) is the first-line chemotherapy for metastatic malignant melanoma without cerebral metastasis. Its clinical and hematological safety is usually good. Hypersensitivity in hepatic failure patients is the most serious side effect described. This was a retrospective study of the prevalence of hypersensitivity in patients treated with DTIC for metastatic melanoma between 11/01/2002 and 10/31/2003. Hypersensitivity was diagnosed in the event of fever, hypereosinophilia (> 500/mm3) with or without liver dysfunction (> twice pre-therapeutic values). Clinical data, DTIC administration modalities, number of courses and clinical and laboratory safety data were recorded. Twenty patients were included, 11 women and 9 men of median age 58.6 years (22-82 years) with multiple metastases in all cases. DTIC was the first-line treatment for 19 patients, being administered for 4 days to 10 patients and for 1 day to the other 10 patients, depending on their overall health status. Five hypersensitivity-like manifestations were observed, all in the 4-day treatment group. In 3 patients, fever and hypereosinophilia were seen without liver dysfunction at D3 of the second course of treatment. In 2 patients, treatment was stopped after the second course because of disease progression. In the third patient, 4 courses were given with recurrence of symptoms, although the latter were controlled during the fifth course with corticosteroids and antihistamines given 15 minutes before the start of treatment. Two patients experienced severe forms of hypersensitivity with fever, hypereosinophilia, liver dysfunction (cytolysis and cholestasis) and delayed medullar aplasia, after the first and second course respectively. In one patient, bone marrow examination showed a block at the promyelocytic stage consistent with a toxic etiology. Treatment with DTIC was stopped, and all signs regressed with symptomatic treatment. Hypersensitivity with DTIC seems to be frequent, being observed in 20

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

PubMed Central

Benson, Al; Yaghmai, Vahid; Costa, Ricardo L. B.; Zhou, Haijun; Behdad, Amir; Kaplan, Jason B.; Sadim, Maureen; Talamantes, Sarah; Kalyan, Aparna

2018-01-01

Pancreatic cancer is the fourth most common cancer death in the United States despite comprising a small percentage of the total number of cancer cases. The estimated 5-year overall survival (OS) for patients with distant metastatic disease is approximately 3%. New treatment options are an unmet need and remain an area of active investigation. A 53-year-old male with metastatic pancreatic cancer presented to the hospital with acute-on-chronic respiratory failure approximately 24 hours after receiving a novel therapeutic combination. Chest imaging showed marked changes as concerning for pneumonitis. Infectious workup was negative. The patient had initial clinical improvement after receiving initial intravenous steroids and oxygen support but eventually deteriorated later opting for supportive measures only. With infection ruled out, drug-induced pneumonitis was felt to be the likely cause of the radiologic and clinical changes. The rapidity of onset of symptoms is the aspect being highlighted in this case. PMID:29808141

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

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

PubMed

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

2016-01-01

Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P < .0001) and less likely to have an underlying condition not typically associated with lung disease (3% vs 20%, P < .0001). Histopathology was performed in only 17.3% of CMV-positive bronchoscopy episodes. When CMV diagnostic methods were evaluated against the comprehensive definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis.

N-Acetylcysteine Attenuates Hexavalent Chromium-Induced Hypersensitivity through Inhibition of Cell Death, ROS-Related Signaling and Cytokine Expression

PubMed Central

Huang, Chien-Cheng; Sheu, Hamm-Ming; Tsai, Jui-Chen; Lin, Chia-Ho; Wang, Ying-Jan; Wang, Bour-Jr

2014-01-01

Chromium hypersensitivity (chromium-induced allergic contact dermatitis) is an important issue in occupational skin disease. Hexavalent chromium (Cr (VI)) can activate the Akt, Nuclear factor κB (NF-κB), and Mitogen-activated protein kinase (MAPK) pathways and induce cell death, via the effects of reactive oxygen species (ROS). Recently, cell death stimuli have been proposed to regulate the release of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1). However, the exact effects of ROS on the signaling molecules and cytotoxicity involved in Cr(VI)-induced hypersensitivity have not yet been fully demonstrated. N-acetylcysteine (NAC) could increase glutathione levels in the skin and act as an antioxidant. In this study, we investigated the effects of NAC on attenuating the Cr(VI)-triggered ROS signaling in both normal keratinocyte cells (HaCaT cells) and a guinea pig (GP) model. The results showed the induction of apoptosis, autophagy and ROS were observed after different concentrations of Cr(VI) treatment. HaCaT cells pretreated with NAC exhibited a decrease in apoptosis and autophagy, which could affect cell viability. In addition, Cr (VI) activated the Akt, NF-κB and MAPK pathways thereby increasing IL-1α and TNF-α production. However, all of these stimulation phenomena could be inhibited by NAC in both of in vitro and in vivo studies. These novel findings indicate that NAC may prevent the development of chromium hypersensitivity by inhibiting of ROS-induced cell death and cytokine expression. PMID:25248126

Isocyanates and respiratory disease: current status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musk, A.W.; Peters, J.M.; Wegman, D.H.

This paper reviews the known respiratory effects of isocyanates. There is good evidence to indicate that isocyanates: cause chemical bronchitis/pneumonitis; are potent pulmonary sensitizers capable of causing isocyanate asthma; cause nonspecific airways disease, including chronic bronchitis; can induce a general asthmatic state; and can cause hypersensitivity pneumonitis. Similar dose-response relationships are seen for both acute and chronic effects. There are plants operating in which exposures are well controlled and in which no respiratory effects can be detected. Suggestions are provided for preplacement assessment and periodic surveillance for workers exposed to these compounds.114 references.

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

PubMed

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

2017-08-01

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

Pneumonic Plague Outbreak, Northern Madagascar, 2011

PubMed Central

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

2015-01-01

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

Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity.

PubMed

Hughes, Dyfrig A; Vilar, F Javier; Ward, Charlotte C; Alfirevic, Ana; Park, B Kevin; Pirmohamed, Munir

2004-06-01

Abacavir, a human immunodeficiency virus-1 (HIV-1) nucleoside-analogue reverse transcriptase inhibitor, causes severe hypersensitivity in 4-8% of patients. HLA B*5701 is a known genetic risk factor for abacavir hypersensitivity in Caucasians. Our aim was to confirm the presence of this genetic factor in our patients, and to determine whether genotyping for HLA B*5701 would be a cost-effective use of healthcare resources. Patients with and without abacavir hypersensitivity were identified from a UK HIV clinic. Patients were genotyped for HLA B*5701, and pooled data used for calculation of test characteristics. The cost-effectiveness analysis incorporated the cost of testing, cost of treating abacavir hypersensitivity, and the cost and selection of alternative antiretroviral regimens. A probabilistic decision analytic model (comparing testing versus no testing) was formulated and Monte Carlo simulations performed. Of the abacavir hypersensitive patients, six (46%) were HLA B*5701 positive, compared to five (10%) of the non-hypersensitive patients (odds ratio 7.9 [95% confidence intervals 1.5-41.4], P = 0.006). Pooling of our data on HLA B*5701 with published data resulted in a pooled odds ratio of 29 (95% CI 6.4-132.3; P < 0.0001). The cost-effectiveness model demonstrated that depending on the choice of comparator, routine testing for HLA B*5701 ranged from being a dominant strategy (less expensive and more beneficial than not testing) to an incremental cost-effectiveness ratio (versus no testing) of Euro 22,811 per hypersensitivity reaction avoided. Abacavir hypersensitivity is associated with HLA B*5701, and pre-prescription pharmacogenetic testing for this appears to be a cost-effective use of healthcare resources.

Pro and Contra: Provocation Tests in Drug Hypersensitivity

PubMed Central

Soyer, Ozge; Sahiner, Umit Murat; Sekerel, Bulent Enis

2017-01-01

Drug provocation test (DPT) is the controlled administration of a drug to diagnose immune- or non-immune-mediated drug hypersensitivity and the last step for accurate recognition of drug hypersensitivity reactions when the previous diagnostic evaluations are negative or unavailable. A DPT is performed only if other conventional tests fail to yield conclusive results. In each clinical presentation, “to provoke or not to provoke” a patient should be decided after careful assessment of the risk–benefit ratio. Well-defined benefits of DPT include confirmative exclusion of diagnoses of drug hypersensitivity and provision of safe alternatives. However, disadvantages such as safety, difficulty in interpretations of results, lack of objective biomarkers, risks of resensitization, efficiency in daily practice, and lack of standardized protocols, are poorly debated. This review summarizes the current published research concerning DPT, with particular emphasis on the advantages and disadvantages of DPT in an evidence-based manner. PMID:28677662

Analysis of dose-volume parameters predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-conformal radiation therapy or IMRT.

PubMed

Kumar, Gaurav; Rawat, Sheh; Puri, Abhishek; Sharma, Manoj Kumar; Chadha, Pranav; Babu, Anand Giri; Yadav, Girigesh

2012-01-01

Multimodality therapy for esophageal cancer can cause various kinds of treatment-related sequelae, especially pulmonary toxicities. This prospective study aims to investigate the clinical and dosimetric parameters predicting lung injury in patients undergoing radiation therapy for esophageal cancer. Forty-five esophageal cancer patients were prospectively analyzed. The pulmonary toxicities (or sequelae) were evaluated by comparing chest X-ray films, pulmonary function tests and symptoms caused by pulmonary damage before and after treatment. All patients were treated with either three-dimensional radiotherapy (3DCRT) or with intensity-modulated radiotherapy (IMRT). The planning dose volume histogram was used to compute the lung volumes receiving more than 5, 10, 20 and 30 Gy (V5, V10, V20, V30) and mean lung dose. V20 was larger in the IMRT group than in the 3DCRT group (p = 0.002). V20 (>15%) and V30 (>20%) resulted in a statistically significant increase in the occurrence of chronic pneumonitis (p = 0.03) and acute pneumonitis (p = 0.007), respectively. The study signifies that a larger volume of lung receives lower doses because of multiple beam arrangement and a smaller volume of lung receives higher doses because of better dose conformity in IMRT plans. Acute pneumonitis correlates more with V30 values, whereas chronic pneumonitis was predominantly seen in patients with higher V20 values.

Pre-clinical methods for detecting the hypersensitivity potential of pharmaceuticals: regulatory considerations.

PubMed

Hastings, K L

2001-02-02

Immune-based systemic hypersensitivities account for a significant number of adverse drug reactions. There appear to be no adequate nonclinical models to predict systemic hypersensitivity to small molecular weight drugs. Although there are very good methods for detecting drugs that can induce contact sensitization, these have not been successfully adapted for prediction of systemic hypersensitivity. Several factors have made the development of adequate models difficult. The term systemic hypersensitivity encompases many discrete immunopathologies. Each type of immunopathology presumably is the result of a specific cluster of immunologic and biochemical phenomena. Certainly other factors, such as genetic predisposition, metabolic idiosyncrasies, and concomitant diseases, further complicate the problem. Therefore, it may be difficult to find common mechanisms upon which to construct adequate models to predict specific types of systemic hypersensitivity reactions. There is some reason to hope, however, that adequate methods could be developed for at least identifying drugs that have the potential to produce signs indicative of a general hazard for immune-based reactions.

Different immune cells mediate mechanical pain hypersensitivity in male and female mice

PubMed Central

Sorge, Robert E.; Mapplebeck, Josiane C.S.; Rosen, Sarah; Beggs, Simon; Taves, Sarah; Alexander, Jessica K.; Martin, Loren J.; Austin, Jean-Sebastien; Sotocinal, Susana G.; Chen, Di; Yang, Mu; Shi, Xiang Qun; Huang, Hao; Pillon, Nicolas J.; Bilan, Philip J.; Tu, Yu Shan; Klip, Amira; Ji, Ru-Rong; Zhang, Ji; Salter, Michael W.; Mogil, Jeffrey S.

2016-01-01

A large and rapidly increasing body of evidence indicates that microglia-neuron signaling is essential for chronic pain hypersensitivity. Here we show using multiple approaches that microglia are not required for mechanical pain hypersensitivity in female mice; female mice achieve similar levels of pain hypersensitivity using adaptive immune cells, likely T-lymphocytes. This sexual dimorphism suggests that male mice cannot be used as proxies for females in pain research. PMID:26120961

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

PubMed

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

2014-05-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

HYPERSENSITIVITY PNEUMONITIS IN A METAL-WORKING ENVIRONMENT. (R825251)

EPA Science Inventory

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

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

Protection against experimental bubonic and pneumonic plague by a recombinant capsular F1-V antigen fusion protein vaccine.

PubMed

Heath, D G; Anderson, G W; Mauro, J M; Welkos, S L; Andrews, G P; Adamovicz, J; Friedlander, A M

1998-07-01

The current human whole-cell vaccine is ineffective against pneumonic plague caused by typical F1 capsule positive (F1+) strains of Yersinia pestis. The authors found this vaccine to also be ineffective against F1-negative (F1-) Y. pestis strains, which have been isolated from a human case and from rodents. For these reasons, the authors developed a recombinant vaccine composed of a fusion protein of F1 with a second protective immunogen, V antigen. This vaccine protected experimental mice against pneumonic as well as bubonic plague produced by either an F1+ or F1- strain of Y. pestis, gave better protection than F1 or V alone against the F1+ strain, and may provide the basis for an improved human plague vaccine.

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

PubMed

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

2017-08-01

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

Protection of mice from fatal bubonic and pneumonic plague by passive immunization with monoclonal antibodies against the F1 protein of Yersinia pestis.

PubMed

Anderson, G W; Worsham, P L; Bolt, C R; Andrews, G P; Welkos, S L; Friedlander, A M; Burans, J P

1997-04-01

Monoclonal antibodies (MAbs) to the fraction 1 (F1) protein of Yersinia pestis protected mice against fatal pneumonic as well as bubonic plague from wild-type F1+ organisms. The rare isolation of a virulent F1- isolate from surviving animals supports earlier studies suggesting that improved vaccines should consist of immunogens to protect against F1- variants. The high degree of protection with IgG MAb suggests that secretory IgA is not required for protection from pneumonic plague.

Effect of Premedications in a Murine Model of Asparaginase Hypersensitivity

PubMed Central

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

2015-01-01

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. PMID:25573198

Comparison of the prevalence and characteristics of food hypersensitivity among adolescent and older women.

PubMed

Fujimori, Anri; Yamashita, Tomomi; Kubota, Masaru; Saito, Hiromi; Takamatsu, Nobue; Nambu, Mitsuhiko

2016-12-01

Although food hypersensitivity is a public health concern, its documentation among the elderly is limited. The current study aims to compare the prevalence and characteristics of food hypersensitivity among adolescent women between aged 18-24 with among older women >50 years of age. 660 female university students between the ages of 18 and 24 who volunteered were enrolled as adolescent subjects. 470 women >50 years old who visited the Health Care Centre of Kyoto Katsura Hospital for health check-ups were enrolled as the older subjects. A questionnaire created by ourselves asking the presence of food hypersensitivity, symptoms, causative food, personal or family history of other allergic disorders was distributed. The prevalence of food hypersensitivity was statistically similar between adolescent (8.2%) and older women (8.9%). Among them, only 24.1% of the adolescent women and 26.2% of the older women had been diagnosed by physicians as having food allergy. The main causative foods (fruits, shellfish and fish) and the manifestations relating to food hypersensitivity were almost identical between adolescent and older women. In both adolescent and older women, food hypersensitivity positive group showed significantly higher prevalence of personal or family history of allergic disorders than that in food hypersensitivity negative group. These data indicate that food hypersensitivity in older women should be given more attention because the prevalence of this condition was as common as that in adolescent women.

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

PubMed

Riehm, Julia M; Löscher, Thomas

2015-07-01

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

An Improved Model for Predicting Radiation Pneumonitis Incorporating Clinical and Dosimetric Variables;Lung cancer; Radiation pneumonitis; Dose-volume histogram; Angiotensin converting enzyme inhibitor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jenkins, Peter, E-mail: peter.jenkins@glos.nhs.uk; Watts, Joanne

2011-07-15

Purpose: Single dose-volume metrics are of limited value for the prediction of radiation pneumonitis (RP) in day-to-day clinical practice. We investigated whether multiparametric models that incorporate clinical and physiologic factors might have improved accuracy. Methods and Materials: The records of 160 patients who received radiation therapy for non-small-cell lung cancer were reviewed. All patients were treated to the same dose and with an identical technique. Dosimetric, pulmonary function, and clinical parameters were analyzed to determine their ability to predict for the subsequent development of RP. Results: Twenty-seven patients (17%) developed RP. On univariate analysis, the following factors were significantly correlatedmore » with the risk of pneumonitis: fractional volume of lung receiving >5-20 Gy, absolute volume of lung spared from receiving >5-15 Gy, mean lung dose, craniocaudal position of the isocenter, transfer coefficient for carbon monoxide (KCOc), total lung capacity, coadministration of angiotensin converting enzyme inhibitors, and coadministration of angiotensin receptor antagonists. By combining the absolute volume of lung spared from receiving >5 Gy with the KCOc, we defined a new parameter termed Transfer Factor Spared from receiving >5 Gy (TFS{sub 5}). The area under the receiver operator characteristic curve for TFS{sub 5} was 0.778, increasing to 0.846 if patients receiving modulators of the renin-angiotensin system were excluded from the analysis. Patients with a TFS{sub 5} <2.17 mmol/min/kPa had a risk of RP of 30% compared with 5% for the group with a TFS{sub 5} {>=}2.17. Conclusions: TFS{sub 5} represents a simple parameter that can be used in routine clinical practice to more accurately segregate patients into high- and low-risk groups for developing RP.« less

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

PubMed

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

2014-01-01

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

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

PubMed

Egan, Joseph R

2010-10-25

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

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

PubMed Central

2010-01-01

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

Probiotics for Prevention of Atopy and Food Hypersensitivity in Early Childhood

PubMed Central

Zhang, Guo-Qiang; Hu, Hua-Jian; Liu, Chuan-Yang; Zhang, Qiao; Shakya, Shristi; Li, Zhong-Yue

2016-01-01

Abstract Most studies investigated probiotics on food hypersensitivity, not on oral food challenge confirmed food allergy in children. The authors systematically reviewed the literature to investigate whether probiotic supplementation prenatally and/or postnatally could reduce the risk of atopy and food hypersensitivity in young children. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and 4 main Chinese literature databases (Wan Fang, VIP, China National Knowledge Infrastructure, and SinoMed) were searched for randomized controlled trials regarding the effect of probiotics on the prevention of allergy in children. The last search was conducted on July 11, 2015. Seventeen trials involving 2947 infants were included. The first follow-up studies were analyzed. Pooled analysis indicated that probiotics administered prenatally and postnatally could reduce the risk of atopy (relative risk [RR] 0.78; 95% confidence interval [CI] 0.66–0.92; I2 = 0%), especially when administered prenatally to pregnant mother and postnatally to child (RR 0.71; 95% CI 0.57–0.89; I2 = 0%), and the risk of food hypersensitivity (RR 0.77; 95% CI 0.61–0.98; I2 = 0%). When probiotics were administered either only prenatally or only postnatally, no effects of probiotics on atopy and food hypersensitivity were observed. Probiotics administered prenatally and postnatally appears to be a feasible way to prevent atopy and food hypersensitivity in young children. The long-term effects of probiotics, however, remain to be defined in the follow-up of existing trials. Still, studies on probiotics and confirmed food allergy, rather than surrogate measure of food hypersensitivity, are warranted. PMID:26937896

Toxic pneumonitis caused by inhalation of hydrocarbon waterproofing spray in two dogs.

PubMed

Young, Brian C; Strom, Adam M; Prittie, Jennifer E; Barton, Linda J

2007-07-01

2 dogs were evaluated because of vomiting and lethargy (a Toy Poodle; dog 1) and acute respiratory distress, vomiting, and anorexia (a Chihuahua; dog 2). Dog 1 had been exposed to a commercial hydrocarbon waterproofing spray 24 hours before the development of clinical signs, and dog 2 was examined 18 hours after exposure to a waterproofing spray containing heptane, a highly flammable liquid hydrocarbon. In both dogs, major gastrointestinal tract abnormalities were ruled out but respiratory status worsened. Thoracic radiography revealed a diffuse interstitial pulmonary pattern, and hypoxemia was detected. Hospitalization for monitoring and care was required for both dogs. The dogs recovered with supportive care, which included administration of oxygen, fluids, and bronchodilators. Additionally, dog 1 received glucocorticoids via inhalation and supplemental enteral nutrition, whereas dog 2 was treated with an antimicrobial. The dogs of this report developed hydrocarbon pneumonitis following exposure to waterproofing sprays. Such sprays contain potentially toxic hydrocarbons. The severity of the adverse effects associated with exposure may have been amplified because the dogs were physically small and were exposed to a relatively large amount of aerosolized spray within small areas. Development of chemical pneumonitis in pet animals is best prevented by application of waterproofing sprays in well-ventilated or outdoor areas from which pets have been excluded. With prolonged hospitalization and considerable monitoring and care, affected dogs can recover from these exposures.

HLA- B*5701 Allele in HIV-infected Indian Children and its Association with Abacavir Hypersensitivity.

PubMed

Manglani, Mamta V; Gabhale, Yashwant R; Lala, Mamatha M; Sekhar, Rohini; More, Dipti

2018-02-15

To determine the prevalence of HLA-B*5701 allele in HIV-infected children, and to find its association with Abacavir hypersensitivity. Children (2 to 18 y) already on, or to be initiated on Abacavir were included for PCR sequencing to detect HLA-B*5701. proportion with HLA B*5701 allele and hypersensitivity with Abacavir. Abacavir was stopped if patient tested positive for HLA-B*5701 allele. 100 children (median age 11 y) were enrolled; 10 were already on Abacavir. HLA-B*5701 positivity was observed in 11 (11%) children. Two of these 11 children developed hypersensitivity after initiation of Abacavir. Abacavir was thereafter stopped in all who tested HLA-B*5701 positive, irrespective of the development of hypersensitivity reaction. HLA-B*5701 allele was present in 11 (11%) of HIV-infected children, of which two developed Abacavir hypersensitivity. None of the patients without the allele developed hypersensitivity.

Dentin hypersensitivity: from diagnosis to a breakthrough therapy for everyday sensitivity relief.

PubMed

Cummins, Diane

2009-01-01

This paper provides an overview of the current knowledge of diagnosis, epidemiology, etiology, and clinical management of dentin hypersensitivity. It summarizes technical approaches to relieve sensitivity in professional and home-use products, with emphasis on the clinical evidence for the efficacy of desensitizing toothpaste, and introduces a new innovative dentifrice technology containing 8% arginine, calcium carbonate, and 1450 ppm fluoride. Dentin hypersensitivity is characterized by short, sharp pain arising from exposed dentin in response to external stimuli which cannot be ascribed to any other form of dental defect or disease. The hydrodynamic theory proposes that pain-producing stimuli cause a change in dentin fluid flow that activates intra-dental nerve fibers, via a mechanoreceptor response, to cause pain. To be hypersensitive, dentin must be exposed and dentin tubules must be open to external stimuli and patent at the pulp. Gingival recession is the primary cause of dentin exposure, and a major predisposing factor for dentin hypersensitivity. Dentin hypersensitivity is a prevalent condition. It has been reported to afflict 15-20% of the adult population, typically 20 to 50-year-olds, with peak incidence between 30 and 39 years. Some studies have reported higher prevalence levels of up to 57%. The incidence of dentin hypersensitivity is expected to rise with changing diets, and as caries and periodontal disease prevention result in improved oral health status, and retention and functionality of the dentition. Treatments to relieve dentin hypersensitivity are based on interruption of the neural response to pain stimuli or occlusion of open tubules to block the hydrodynamic mechanism. Effective and robust dentin occlusion offers the greatest prospect for instant and lasting relief of dentin hypersensitivity. In particular, materials which can coat exposed dentin surfaces, in addition to plugging and sealing open dentin tubules, offer the intriguing

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

PubMed Central

2018-01-01

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

Application of Diode Laser in the Treatment of Dentine Hypersensitivity.

PubMed

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

2016-12-01

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. The aim of this research was to examine the effects of treatment of hypersensitive dental cervix with diode laser. 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. 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). Within the scope of the conducted study, laser therapy has provided extremely safe and effective results in the treatment of cervical dentine hypersensitivity.

Aspirin and Nonsteroidal Antiinflammatory Drugs Hypersensitivity and Management.

PubMed

Modena, Brian; White, Andrew A; Woessner, Katharine M

2017-11-01

Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) are widely used in the United States and throughout the world for a variety of indications. Several unique hypersensitivity syndromes exist to this class of medications, making them one of the common reasons for consultation to the allergist. The lack of any laboratory-based diagnostic studies to assist in identifying the culprits in these reactions make evaluation of aspirin and NSAID hypersensitivity challenging. Identifying patients appropriate for oral challenge and/or desensitization protocols is the standard pragmatic approach to this issue when it arises. Copyright © 2017 Elsevier Inc. All rights reserved.

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

NASA Technical Reports Server (NTRS)

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

1993-01-01

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

An unexpected cause of an acute hypersensitivity reaction during recovery from anaesthesia.

PubMed

Thong, C L; Lambros, M; Stewart, M G; Kam, P C A

2005-08-01

Acute hypersensitivity reactions to chlorhexidine in the operating room are probably more likely to occur during the early phases of anaesthesia because chlorhexidine is often used for cleaning the surgical field or during placement of indwelling catheters. We report a case of an acute hypersensitivity reaction that occurred in the post anaesthetic care unit. Subsequent skin testing suggested sensitivity to chlorhexidine, which had been applied over the vaginal mucosa at the end of surgery. Relevant issues in the investigation of acute hypersensitivity reactions in the post anaesthetic period are discussed.

Hypersensitivity to lipid transfer protein is frequently associated with chronic urticaria.

PubMed

Asero, R

2011-02-01

Sparse clinical observations suggest a possible association between food allergy to lipid transfer protein (LTP) and chronic urticaria (CU). To investigate the possible association between LTP hypersensitivity and CU. History of CU, and/or of NSAID hypersensitivity was prospectively assessed in 75 consecutive LTP-allergic subjects (M/F 27/48; age 33.6 years); those with positive histories underwent an autologous serum skin test (ASST). 100 atopic subjects not sensitized to LTP and 100 subjects with chronic urticaria served as controls. 16/75 (21%) patients had a history of current or past CU. 7 (9%) had a history of NSAID-induced urticaria, and the ASST scored positive in 9/11 patients (82%). By comparison with atopic controls patients showed a significantly higher prevalence of CU (21% vs 6%; p < 0.01), a > 4 times more frequent history of NSAID hypersensitivity (9% vs 2%), and a higher prevalence of females (p< 0.05). In contrast, patients and controls with chronic urticaria showed a similar sex distribution, prevalence of positive ASST, and prevalence of NSAID hypersensitivity. An unidirectional association between LTP hypersensitivity and chronic urticaria seems to exist. The reasons for this are unclear although it is possible that CU makes mast cells more easily excitable by food allergens. Further, it has been shown that NSAIDs may up-regulate type 1 allergic responses to foods, possibly increasing permeability of the gut mucosa.

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

PubMed

Prasertvit, Piyatida; Chareonyingwattana, Angkana; Wattanakrai, Penpun

2017-12-01

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

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

PubMed

Mühlmeier, G; Hausch, R; Maier, H

2015-10-01

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

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

Acute hypersensitivity reactions associated with administration of crotalidae polyvalent immune Fab antivenom.

PubMed

Cannon, Robert; Ruha, Anne-Michelle; Kashani, John

2008-04-01

Acute hypersensitivity reactions are well known to occur with the administration of the Antivenin (Crotalidae) Polyvalent (Wyeth Laboratories, Marietta, PA). Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV, Protherics, Inc., Brentwood, TN) was introduced in 2001, and early studies reported a hypersensitivity reaction rate up to 19%. We describe the incidence of acute hypersensitivity reactions to FabAV in patients bitten by rattlesnakes. This was a nonconcurrent observational cohort study, with data obtained by chart review of all patients admitted to our service for rattlesnake bites from July 2000 to June 2004. The study was conducted at an urban Level I trauma center and urban children's hospital. All patients treated with FabAV were included. Those who received no antivenom or who were treated with Antivenin (Crotalidae) Polyvalent were excluded. The main outcome variable was whether an acute hypersensitivity reaction developed. Ninety-three patients were included in the review (72 male and 21 female patients). The mean age was 34.5 years (range 16 months to 91 years), and the mean dose of antivenom was 12 vials (range 4 to 32 vials). The incidence of acute hypersensitivity reactions was 5 of 93, or 5.4%. Four patients developed a mild reaction that was easily treated and were able to finish the full course of antivenom. Only 1 patient developed a reaction that prevented further antivenom administration. FabAV appears to be associated with a lower incidence of acute hypersensitivity than initially reported. Most reactions are mild and easily treated and do not preclude further dosing of antivenom.

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

PubMed

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

2008-01-01

A 78-year-old man was admitted to our hospital for irradiation therapy of non-resectable primary lung squamous cell carcinoma of the right middle lobe (T3N2M0). The Linac irradiation through opposing 2 gates (2Gy per day and 60Gy in total) was performed to the affected area including the metastatic right hilar and mediastinal lymphadenopathy. One week after completing the irradiation therapy, fever developed with infiltrates in the area from the right middle lobe to the right lower lobe, which did not necessarily coincide with the irradiated area. Antibiotic therapies were not effective. Both the serum LDH level and eosinophil count in the peripheral blood increased. Bronchoalveolar lavage was performed at the right B8, and differential cell counts of the lavage fluid were: macrophages, 17%; lymphocytes, 60%; neutrophils, 5%; and eosinophils, 18%. No significant organisms were obtained by culture of the lavage fluid. The %VC and DLCO/VA became lower than before the irradiation therapy. Thus, the patient was given a diagnosis of radiation pneumonitis. Treatment with 40mg/day oral prednisolone was commenced with a stepwise dose-reduction (5mg every two weeks) until reaching the maintenance dose of 15mg/day. The serum LDH level and blood eosinophil count recovered promptly to the normal range. The pulmonary infiltrates and the lung functions substantially improved. There have been few reports of radiation pneumonitis in which eosinophil counts increased in peripheral blood and bronchoalveolar lavage fluid after irradiation therapy. In the present case report, the possible mechanisms for the irradiation-induced eosinophilia were also reviewed.

Agricultural lung diseases.

PubMed Central

Kirkhorn, S R; Garry, V F

2000-01-01

Agriculture is considered one of the most hazardous occupations. Organic dusts and toxic gases constitute some of the most common and potentially disabling occupational and environmental hazards. The changing patterns of agriculture have paradoxically contributed to both improved working conditions and increased exposure to respiratory hazards. Animal confinement operations with increasing animal density, particularly swine confinement, have contributed significantly to increased intensity and duration of exposure to indoor air toxins. Ongoing research has implicated bacterial endotoxins, fungal spores, and the inherent toxicity of grain dusts as causes of upper and lower airway inflammation and as immunologic agents in both grain and animal production. Animal confinement gases, particularly ammonia and hydrogen sulfide, have been implicated as additional sources of respiratory irritants. It has become evident that a significant percentage of agricultural workers have clinical symptoms associated with long-term exposure to organic dusts and animal confinement gases. Respiratory diseases and syndromes, including hypersensitivity pneumonitis, organic dust toxic syndrome, chronic bronchitis, mucous membrane inflammation syndrome, and asthmalike syndrome, result from ongoing acute and chronic exposures. In this review we focus upon the emerging respiratory health issues in a changing agricultural economic and technologic environment. Environmental and occupational hazards and exposures will be emphasized rather than clinical diagnosis and treatment. Methods of prevention, from both engineering controls and personal respiratory perspectives, are also addressed. PMID:10931789

Cough Hypersensitivity Syndrome: A Few More Steps Forward

PubMed Central

Song, Woo-Jung

2017-01-01

Cough reflex is a vital protective mechanism against aspiration, but when dysregulated, it can become hypersensitive. In fact, chronic cough is a significant medical problem with a high degree of morbidity. Recently, a unifying paradigm of cough hypersensitivity syndrome has been proposed. It represents a clinical entity in which chronic cough is a major presenting problem, regardless of the underlying condition. Although it remains a theoretical construct, emerging evidence suggests that aberrant neurophysiology is the common etiology of this syndrome. Recent success in randomized clinical trials using a P2X3 receptor antagonist is the first major advance in the therapeutics of cough in the past 30 years; it at last provides a strategy for treating intractable cough as well as an invaluable tool for dissecting the mechanism underpinning cough hypersensitivity. Additionally, several cough measurement tools have been validated for use and will help assess the clinical relevance of cough in various underlying conditions. Along with this paradigm shift, our understanding of cough mechanisms has improved during the past decades, allowing us to continue to take more steps forward in the future. PMID:28677352

Lymphocyte blastogenic responses to inciting food allergens in dogs with food hypersensitivity.

PubMed

Ishida, Rinei; Masuda, Kenichi; Kurata, Keigo; Ohno, Koichi; Tsujimoto, Hajime

2004-01-01

Lymphocyte blastogenic responses against food allergens in dogs with food hypersensitivity were evaluated in this study. Eleven dogs with food hypersensitivity, based on food elimination and oral food provocation tests and allergic responses to food allergens, were examined by various tests such as intradermal testing, antigen-specific IgE testing, and lymphocyte blastogenic responses. The number and kinds of food allergens identified as positive by these tests were compared with the offending food allergens that were found in an oral food provocation test. In 9 (82%) of the 11 dogs with food hypersensitivity, there was close agreement for positive allergens between the results of lymphocyte blastogenic responses and oral food provocation test; however, there was little agreement for intradermal and IgE testing of the positive allergens with those of the oral food provocation test (11% and 31%, respectively). In the 9 dogs, the stimulation indices of lymphocyte blastogenic responses increased to 2.0-10.1 upon food provocation but decreased significantly to 0.7-1.4 upon feeding the elimination diet until clinical signs disappeared. These results indicate that lymphocyte blastogenic responses may fluctuate because of exposure to offending food allergens in dogs with food hypersensitivity. Lymphocytes reactive to food allergens may play an important role in the pathogenesis of food hypersensitivity in dogs.

Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection.

PubMed

Descamps, V; Mahe, E; Houhou, N; Abramowitz, L; Rozenberg, F; Ranger-Rogez, S; Crickx, B

2003-05-01

Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.

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

PubMed

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

2012-01-01

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

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

PubMed

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

2017-02-01

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

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

[Preventive dentistry 3. Prevalence, aetiology and diagnosis of dentine (hyper)sensitivity].

PubMed

van der Weijden, F N; van Loveren, C; Slot, D E; van der Weijden, G A

2017-02-01

Many people sometimes experience pain when they inhale breath across the cingula, or sensitivity and/or pain when they eat ice cream, for example. In some cases, however, this can become seriously unpleasant. In those cases, one can speak of dentine hypersensitivity. In Europe, an average of 27% of the population suffers from this. Dentine hypersensitivity is characterised by a short, sharp pain reaction after a warm or cold sensation. The external sensation causes an accelerated or converse flow of fluid in the dentinal tubules that excites the extremities of the nerve cells, which results in the sensation pain. For the external sensation, it is necessary that the cingula are exposed and the dentinal tubules are open. Dentine hypersensitivity is diagnosed after other possibilities have been eliminated.

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

Case of immediate hypersensitivity to beer.

PubMed

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

2016-06-01

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

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

PubMed

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

2004-02-01

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

Electromagnetic hypersensitivity: fact or fiction?

PubMed

Genuis, Stephen J; Lipp, Christopher T

2012-01-01

As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home or workplace; others suggest that electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various organizations including the World Health Organization as well as some nation states are carefully exploring this clinical phenomenon in order to better explain the rising prevalence of non-specific, multi-system, often debilitating symptoms associated with non-ionizing EMR exposure. As well as an assortment of physiological complaints, patients diagnosed with EHS also report profound social and personal challenges, impairing their ability to function normally in society. This paper offers a review of the sparse literature on this perplexing condition and a discussion of the controversy surrounding the legitimacy of the EHS diagnosis. Recommendations are provided to assist health professionals in caring for individuals complaining of EHS. Copyright © 2011 Elsevier B.V. All rights reserved.

Field Evaluation of Solvent-Free Sampling with Di-n-butylamine for the Determination of Airborne Monomeric and Oligomeric 1,6-Hexamethylene Diisocyanate

DTIC Science & Technology

2014-03-27

cause contact dermatitis , asthma, and hypersensitivity pneumonitis; the most common adverse health outcome associated with isocyanate exposure is...linked to allergic contact dermatitis in humans and respiratory sensitization in animals. Chronic dermal exposure has resulted in skin irritation and...derivatization stabilizes the highly reactive isocyanates and enhances recovery of the isocyanates that do not come into contact with the derivatization

An algorithm for treatment of patients with hypersensitivity reactions after vaccines.

PubMed

Wood, Robert A; Berger, Melvin; Dreskin, Stephen C; Setse, Rosanna; Engler, Renata J M; Dekker, Cornelia L; Halsey, Neal A

2008-09-01

Concerns about possible allergic reactions to immunizations are raised frequently by both patients/parents and primary care providers. Estimates of true allergic, or immediate hypersensitivity, reactions to routine vaccines range from 1 per 50000 doses for diphtheria-tetanus-pertussis to approximately 1 per 500000 to 1000000 doses for most other vaccines. In a large study from New Zealand, data were collected during a 5-year period on 15 marketed vaccines and revealed an estimated rate of 1 immediate hypersensitivity reaction per 450000 doses of vaccine administered. Another large study, conducted within the Vaccine Safety Datalink, described a range of reaction rates to >7.5 million doses. Depending on the study design and the time after the immunization event, reaction rates varied from 0.65 cases per million doses to 1.53 cases per million doses when additional allergy codes were included. For some vaccines, particularly when allergens such as gelatin are part of the formulation (eg, Japanese encephalitis), higher rates of serious allergic reactions may occur. Although these per-dose estimates suggest that true hypersensitivity reactions are quite rare, the large number of doses that are administered, especially for the commonly used vaccines, makes this a relatively common clinical problem. In this review, we present background information on vaccine hypersensitivity, followed by a detailed algorithm that provides a rational and organized approach for the evaluation and treatment of patients with suspected hypersensitivity. We then include 3 cases of suspected allergic reactions to vaccines that have been referred to the Clinical Immunization Safety Assessment network to demonstrate the practical application of the algorithm.

Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions.

PubMed

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.

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

PubMed

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

2010-12-30

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

Assessment of Workers' Exposure to Grain Dust and Bioaerosols During the Loading of Vessels' Hold: An Example at a Port in the Province of Québec.

PubMed

Marchand, Geneviève; Gardette, Marie; Nguyen, Kiet; Amano, Valérie; Neesham-Grenon, Eve; Debia, Maximilien

2017-08-01

Longshoremen are exposed to large amounts of grain dust while loading of grain into the holds of vessels. Grain dust inhalation has been linked to respiratory diseases such as chronic bronchitis, hypersensitivity, pneumonitis, and toxic pneumonitis. Our objective was to characterize the exposure of longshoremen to inhalable and total dust, endotoxins, and cultivable bacteria and fungi during the loading of grain in a vessel's hold at the Port of Montreal in order to assess the potential health risks. Sampling campaigns were conducted during the loading of two different types of grain (wheat and corn). Environmental samples of microorganisms (bacteria, fungus, and actinomycetes) were taken near the top opening of the ship's holds while personal breathing zone measurements of dust and endotoxins were sampled during the worker's 5-hour shifts. Our study show that all measurements are above the recommendations with concentration going up to 390 mg m-3 of total dust, 89 mg m-3 of inhalable fraction, 550 000 EU m-3 of endotoxins, 20 000 CFU m-3 of bacteria, 61 000 CFU m-3 of fungus and 2500 CFU m-3 of actinomycetes. In conclusion, longshoremen are exposed to very high levels of dust and of microorganisms and their components during grain loading work. Protective equipment needs to be enforced for all workers during such tasks in order to reduce their exposure. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Cracking the egg: An insight into egg hypersensitivity.

PubMed

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

2015-08-01

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

Upregulation of calprotectin in mild IgE-mediated ovalbumin hypersensitivity

PubMed Central

Wang, Junli; Ma, Jingqiu; Sheng, Xiaoyang

2017-01-01

Calprotectin, also known as S100A8/A9, has been linked to gut inflammation caused by IgE-mediated food hypersensitivities, but the pathophysiologic abnormalities it causes remain to be determined. We created a mild food hypersensitivity model through oral gavage of ovalbumin in Norway brown rats without using immune adjuvant. Changes in the levels of calprotectin and inflammation-associated cytokines were then observed over time. We found that fecal calprotectin as well as jejunal and liver TLR4, TNF-α, NF-κB, IL-1β, and IL-6 were upregulated in hypersensitive rats. Additionally, the influence of calprotectin on CD4+ T and dendritic cells was observed by co-culturing CD4+ T cells with dendritic cells, which revealed a shift toward increased Th2 T cells in calprotectin-treated cultures. These results suggest that calprotectin, along with other inflammatory factors, promotes the inflammation seen in mild food allergy. PMID:28454097

Immunological diagnosis of cutaneous-pulmonary hypersensitivity vasculitis.

PubMed

Skjodt, Neil M; Elliot, Tracey L; Puttagunta, Lakshmi; Yacyshyn, Elaine A; Tron, Victor A

2007-11-01

A 47-year-old woman had episodic dyspnoea, fatigue, chest radiograph opacifications, and palpable purpura whose biopsy showed leucocytoclastic vasculitis. Negative immunoglobulin A immunofluorescence staining and clinical exclusion of other disorders narrowed her diagnosis to cutaneous pulmonary hypersensitivity vasculitis.

An approach to natalizumab hypersensitivity: a case series of induction of tolerance.

PubMed

Camacho-Halili, Marie; George, Roxanne; Gottesman, Malcolm; Davis-Lorton, Mark

2011-02-01

Induction of tolerance protocols have been applied successfully to manage allergic reactions to many medications. Hypersensitivity reactions to natalizumab (TYSABRI®) have been recognized as a growing problem. In circumstances where a hypersensitivity reaction to a medication has occurred, but no suitable alternative exists, drug induction of tolerance protocols may be considered. Drug induction of tolerance protocols were performed in three patients with prior hypersensitivity reactions to natalizumab. All three patients tolerated the protocol without adverse reactions, allowing for the safe reintroduction of natalizumab. To conclude, this case series demonstrates success with an induction of tolerance procedure to a highly effective biological agent for multiple sclerosis, in patients with allergic reactions to natalizumab.

Toll-Like Receptor 4 in Paraventricular Nucleus Mediates Visceral Hypersensitivity Induced by Maternal Separation

PubMed Central

Tang, Hui-Li; Zhang, Gongliang; Ji, Ning-Ning; Du, Lei; Chen, Bin-Bin; Hua, Rong; Zhang, Yong-Mei

2017-01-01

Neonatal maternal separation (MS) is a major early life stress that increases the risk of emotional disorders, visceral pain perception and other brain dysfunction. Elevation of toll-like receptor 4 (TLR4) signaling in the paraventricular nucleus (PVN) precipitates early life colorectal distension (CRD)-induced visceral hypersensitivity and pain in adulthood. The present study aimed to investigate the role of TLR4 signaling in the pathogenesis of postnatal MS-induced visceral hypersensitivity and pain during adulthood. The TLR4 gene was selectively knocked out in C57BL/10ScSn mice (Tlr4-/-). MS was developed by housing the offspring alone for 6 h daily from postnatal day 2 to day 15. Visceral hypersensitivity and pain were assessed in adulthood. Tlr4+/+, but not Tlr4-/-, mice that had experienced neonatal MS showed chronic visceral hypersensitivity and pain. TLR4 immunoreactivity was observed predominately in microglia in the PVN, and MS was associated with an increase in the expression of protein and/or mRNA levels of TLR4, corticotropin-releasing factor (CRF), CRF receptor 1 (CRFR1), tumor necrosis factor-α, and interleukin-1β in Tlr4+/+ mice. These alterations were not observed in Tlr4-/- mice. Local administration of lipopolysaccharide, a TLR4 agonist, into the lateral cerebral ventricle elicited visceral hypersensitivity and TLR4 mRNA expression in the PVN, which could be prevented by NBI-35965, an antagonist to CRFR1. The present results indicate that neonatal MS induces a sensitization and upregulation of microglial TLR4 signaling activity, which facilitates the neighboring CRF neuronal activity and, eventually, precipitates visceral hypersensitivity in adulthood. Highlights (1)Neonatal MS does not induce chronic visceral hypersensitivity and pain in Tlr4-/- mice.(2)Neonatal MS increases the expression of TLR4 mRNA, CRF protein and mRNA, CRFR1 protein, TNF-α protein, and IL-1β protein in Tlr4+/+ mice.(3)TLR4 agonist LPS (i.c.v.) elicits visceral

COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice

PubMed Central

Vardeh, Daniel; Wang, Dairong; Costigan, Michael; Lazarus, Michael; Saper, Clifford B.; Woolf, Clifford J.; FitzGerald, Garret A.; Samad, Tarek A.

2009-01-01

A cardinal feature of peripheral inflammation is pain. The most common way of managing inflammatory pain is to use nonsteroidal antiinflammatory agents (NSAIDs) that reduce prostanoid production, for example, selective inhibitors of COX2. Prostaglandins produced after induction of COX2 in immune cells in inflamed tissue contribute both to the inflammation itself and to pain hypersensitivity, acting on peripheral terminals of nociceptors. COX2 is also induced after peripheral inflammation in neurons in the CNS, where it aids in developing a central component of inflammatory pain hypersensitivity by increasing neuronal excitation and reducing inhibition. We engineered mice with conditional deletion of Cox2 in neurons and glial cells to determine the relative contribution of peripheral and central COX2 to inflammatory pain hypersensitivity. In these mice, basal nociceptive pain was unchanged, as was the extent of peripheral inflammation, inflammatory thermal pain hypersensitivity, and fever induced by lipopolysaccharide. By contrast, peripheral inflammation–induced COX2 expression in the spinal cord was reduced, and mechanical hypersensitivity after both peripheral soft tissue and periarticular inflammation was abolished. Mechanical pain is a major symptom of most inflammatory conditions, such as postoperative pain and arthritis, and induction of COX2 in neural cells in the CNS seems to contribute to this. PMID:19127021

Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats.

PubMed

Koizuka, Shiro; Obata, Hideaki; Sasaki, Masayuki; Saito, Shigeru; Goto, Fumio

2005-05-01

Systemic ketamine suppresses several types of chronic pain. Although ketamine is used as a general anesthetic agent, the analgesic effect of systemic ketamine for early-stage postoperative pain is not clear. We investigated the efficacy and mechanism of systemic ketamine in a rat model of postoperative pain. An incision was made in the plantar aspect of the left hind paw in male Wistar rats. Mechanical hypersensitivity was measured using calibrated von Frey filaments. The anti-hypersensitivity effect of systemic or intrathecal administration of ketamine was determined every hour after making the incision. We examined the effects of intrathecal pretreatment with yohimbine, an alpha2-adrenoceptor antagonist, and methysergide, a serotonergic receptor antagonist, on the anti-hypersensitivity effect of ketamine. We also examined the effect of systemic ketamine on the c-fos immunoreactivity in the spinal cord. Systemic administration of ketamine at doses from 3 to 30 mg.kg(-1) produced anti-hypersensitivity effects in a dose-dependent manner. Intrathecal administration of ketamine had no effect. There was no significant difference between effects of pre- and post-incisional administration. Intrathecal pretreatment with yohimbine (10 microg) or methysergide (15 microg) completely reversed the anti-hypersensitivity effects of systemic ketamine. Systemic ketamine reduced fos expression in laminae I-II in the dorsal horn of the lumbar spinal cord ipsilateral to the paw incision. The results suggest that systemic administration of ketamine perioperatively suppresses early-stage postoperative pain via monoaminergic descending inhibitory pathways.

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

PubMed

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

2015-09-01

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

[Dentinal hypersensitivity in periodontal disease. Aetiology Aetiology--management].

PubMed

Andronikaki-Faldani, A; Kamma, I

1988-01-01

The exposure of dentine has a multifactoral aetiology and pain may frequently be elicited by a number of stimuli. Management of dentinal hypersensitivity tends to be empirical because of the lack of knowledge concerning the mechanism of pain transmission through dentine. Nevertheless, whichever theory proves to be correct, occlusion of dentinal tubules would appear an essential prerequisite for an effective desensitising agent. A large number of compounds as well as iontophoresis have been employed in the management of dentinal hypersensitivity. These desensitising agents are: sodium, fluoride, stannous fluoride, sodium monofluorophosphate, strontium chloride, calcium hydroxide, potassium nitrate, silver nitrate, formalin, corticosteroids, resins, varnishes and glass ionomers. The most effective of the compounds mentioned above, are fluorides used as gels, varnishes, mouthwashes or toothpastes, strontium chloride and potassium nitrate.

Methyl methacrylate and respiratory sensitization: A Critical review

PubMed Central

Borak, Jonathan; Fields, Cheryl; Andrews, Larry S; Pemberton, Mark A

2011-01-01

Methyl methacrylate (MMA) is a respiratory irritant and dermal sensitizer that has been associated with occupational asthma in a small number of case reports. Those reports have raised concern that it might be a respiratory sensitizer. To better understand that possibility, we reviewed the in silico, in chemico, in vitro, and in vivo toxicology literature, and also epidemiologic and occupational medicine reports related to the respiratory effects of MMA. Numerous in silico and in chemico studies indicate that MMA is unlikely to be a respiratory sensitizer. The few in vitro studies suggest that MMA has generally weak effects. In vivo studies have documented contact skin sensitization, nonspecific cytotoxicity, and weakly positive responses on local lymph node assay; guinea pig and mouse inhalation sensitization tests have not been performed. Cohort and cross-sectional worker studies reported irritation of eyes, nose, and upper respiratory tract associated with short-term peaks exposures, but little evidence for respiratory sensitization or asthma. Nineteen case reports described asthma, laryngitis, or hypersensitivity pneumonitis in MMA-exposed workers; however, exposures were either not well described or involved mixtures containing more reactive respiratory sensitizers and irritants.The weight of evidence, both experimental and observational, argues that MMA is not a respiratory sensitizer. PMID:21401327

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

PubMed

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

2017-01-01

Pneumonic plague is the most deadly form of infection caused by Yersinia pestis and can progress extremely fast. However, our understanding on the host transcriptomic response to pneumonic plague is insufficient. Here, we used RNA-sequencing technology to analyze transcriptomic responses in mice infected with fully virulent strain 201 or EV76, a live attenuated vaccine strain lacking the pigmentation locus. Approximately 600 differentially expressed genes (DEGs) were detected in lungs from both 201- and EV76-infected mice at 12h post-infection (hpi). DEGs in lungs of 201-infected mice exceeded 2000 at 48hpi, accompanied by sustained large numbers of DEGs in the liver and spleen; however, limited numbers of DEGs were detected in those organs of EV-infected mice. Remarkably, DEGs in lungs were significantly enriched in critical immune responses pathways in EV76-infected but not 201-infected mice, including antigen processing and presentation, T cell receptor signaling among others. Pathological and bacterial load analyses confirmed the rapid systemic dissemination of 201-infection and the confined EV76-infection in lungs. Our results suggest that fully virulent Y. pestis inhibits both the innate and adaptive immune responses that are substantially stimulated in a self-limited infection, which update our holistic views on the transcriptomic response to pneumonic plague. Copyright © 2016 Elsevier GmbH. All rights reserved.

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…

Functional dyspepsia: The role of visceral hypersensitivity in its pathogenesis

PubMed Central

Keohane, John; Quigley, Eamonn M M

2006-01-01

Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD. PMID:16718751

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.

Systemic lupus erythematosus (SLE) pneumonitis mimicking swine influenza pneumonia during the swine influenza (H1N1) pandemic.

PubMed

Cunha, Burke A; Syed, Uzma; Mickail, Nardeen

2011-01-01

We present a young woman with a negative medical history who presented with acute systemic lupus erythematosus (SLE) pneumonitis mimicking swine influenza (H1N1) pneumonia. Because this case occurred during the H1N1 pandemic, the initial diagnostic impression was of H1N1 pneumonia. Although her clinical and laboratory findings were consistent with the diagnosis of H1N1 pneumonia, e.g., fever, sore throat, dry cough, arthralgias, myalgias, thrombocytopenia, relative lymphopenia, and elevated serum transaminases, some findings suggested an alternate diagnosis, e.g., leukopenia, a highly elevated erythrocyte sedimentation rate, highly elevated serum ferritin levels, elevated antinuclear antibody (ANA) levels, and double-stranded (DS) DNA titers. Her chest x-ray showed an accentuation of basilar lung markings, with a small pleural effusion similar to the chest x-ray findings of early H1N1 pneumonia. Initially, her headaches were thought to be related to central nervous system manifestations of H1N1. After laboratory test results demonstrated elevated ANA and anti-DS DNA titers, she was diagnosed with acute SLE pneumonitis. The take-home lesson for clinicians is that other infectious diseases, e.g., human parainfluenza virus or Legionnaires' disease, can mimic H1N1 pneumonia during an influenza pandemic. Excluding asthma, congestive heart failure, exacerbations of acute bronchitis, chronic obstructive pulmonary disorder, and pulmonary interstitial disease, noninfectious mimics of H1N1 are extremely rare. To the best of our knowledge, this is the first reported case of de novo SLE pneumonitis mimicking H1N1 pneumonia during the swine influenza pandemic. Copyright © 2011 Elsevier Inc. All rights reserved.

Predictive factors for acute radiation pneumonitis in postoperative intensity modulated radiation therapy and volumetric modulated arc therapy of esophageal cancer.

PubMed

Zhao, Yaqin; Chen, Lu; Zhang, Shu; Wu, Qiang; Jiang, Xiaoqin; Zhu, Hong; Wang, Jin; Li, Zhiping; Xu, Yong; Zhang, Ying Jie; Bai, Sen; Xu, Feng

2015-01-01

Radiation pneumonitis (RP) is a common side reaction in radiotherapy for esophageal cancer. There are few reports about RP in esophageal cancer patients receiving postoperative intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). This study aims to analyze clinical or dosimetric factors associated with RP, and provides data for radiotherapy planning. We reviewed 68 postoperative esophageal cancer patients who were treated with radiotherapy at the West China Hospital from October 2010 to November 2012 to identify any correlation between the clinical or dosimetric parameters and acute radiation pneumonitis (ARP) or severe acute radiation pneumonitis (SARP) by t-test, chi-square test, and logistic regression analysis. Of the 68 patients, 33 patients (48.5%) developed ARP, 13 of which (19.1%) developed SARP. Of these 33 patients, 8 (11.8%), 12 (17.6%), 11 (16.2%), and 2 (2.9%) patients were grade 1, 2, 3, and 4 ARP, respectively. Univariate analysis showed that lung infection during radiotherapy, use of VMAT, mean lung dose (MLD), and dosimetric parameters (e.g. V20, V30) are significantly correlated with RP. Multivariate analysis found that lung infection during radiotherapy, MLD ≥ 12 Gy, and V30 ≥ 13% are significantly correlated with an increased risk of RP. Lung infection during radiotherapy and low radiation dose volume distribution were predictive factors associated with RP and should be accounted for during radiation planning.

Anticonvulsant hypersensitivity syndrome. In vitro assessment of risk.

PubMed Central

Shear, N H; Spielberg, S P

1988-01-01

Arene oxide metabolites of aromatic anticonvulsants (phenytoin, phenobarbital, and carbamazepine) may be involved in the pathogenesis of hypersensitivity reactions. We investigated 53 patients with clinical sensitivity to anticonvulsants by exposing their lymphocytes in vitro to drug metabolites generated by a murine hepatic microsomal system. The diagnosis of a hypersensitivity reaction was corroborated by in vitro rechallenge for each drug (phenytoin, n = 34; phenobarbital, n = 22; carbamazepine, n = 25) when cytotoxicity (% dead cells) exceeded 3 SD above the mean result for controls. Cross-reactivity among the drugs was noted. 7 out of 10 patients who had received all three anticonvulsants had adverse reactions to each. 40 out of 50 patients tested to all three drugs in vitro were positive to each. Adverse reactions were indistinguishable among anti-convulsants. Skin rash (87%), fever (94%), hepatitis (51%), and hematologic abnormalities (51%) were common clinical features of each drug. 62% of reactions involved more than two organs. Cells from patients' parents exhibited in vitro toxicity that was intermediate between values for controls and patients. In vitro testing can help diagnose hypersensitivity to anticonvulsants. Cells from patients may also be used for prospective individualization of therapy to decrease risk of adverse reaction. Cross-reactivity among the major anticonvulsants is common and should be considered before deciding on alternative therapy. Images PMID:3198757

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.

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

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.

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

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

PubMed

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

2013-01-01

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

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.

Fatal hypersensitivity reaction to an oral spray of flurbiprofen: a case report.

PubMed

Calapai, G; Imbesi, S; Cafeo, V; Ventura Spagnolo, E; Minciullo, P L; Caputi, A P; Gangemi, S; Milone, L

2013-08-01

Safety of the anti-inflammatory drug flurbiprofen is comparable with that of other non-steroidal anti-inflammatory drugs of the propionic acid class, which are commonly associated with gastrointestinal and renal side effects. Here we report a case of a fatal hypersensitivity reaction to an oral spray of flurbiprofen taken for sore throat. A 29-year-old man came to the emergency care unit reporting sore throat with an intense burning sensation associated with fever. Pharyngotonsillitis was diagnosed, and local treatment with oral flurbiprofen spray was prescribed. Immediately after using the spray, the patient experienced a severe reaction characterized by serious dyspnoea, followed by death. The cause of death was heart failure with acute asphyxia from oedema of the glottis. The cause of death was concluded to be hypersensitivity to flurbiprofen spray. Oral propionic acid derivatives have been associated with a relatively high frequency of allergic reactions. However, allergy to flurbiprofen has rarely been documented. Scientific literature reports two relevant cases of hypersensitivity reaction to flurbiprofen: in one case, a patient presented with a maculopapular rash 48 h after having taken oral flurbiprofen followed by angio-oedema and hypotension. In another case, a single oral dose of flurbiprofen caused itching and swelling around the eyes, redness and increased lacrimation. We describe, for the first time, a fatal case of hypersensitivity reaction to flurbiprofen oral spray. Hypersensitivity reactions to flurbiprofen are infrequent; however, health professionals should be aware of potential adverse reactions, even during topical administration as oral spray. © 2013 John Wiley & Sons Ltd.

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

PubMed

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

2011-06-01

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

Occupational asthma in the commercial fishing industry: a case series and review of the literature.

PubMed

Lucas, David; Lucas, Raymond; Boniface, Keith; Jegaden, Dominique; Lodde, Brice; Dewitte, Jean-Ariel

2010-01-01

We present a case series of snow crab-induced occupational asthma (OA) from a fishing and processing vessel, followed by a review of OA in the commercial fishing industry. OA is typically caused from an IgE-mediated hypersensitivity reaction after respiratory exposure to aerosolized fish and shellfish proteins. It more commonly occurs due to crustaceans, but molluscs and fin fish are implicated as well. Standard medical therapy for asthma may be used acutely; however, steps to reduce atmospheric allergen concentrations in the workplace have proven to be preventive for this disease.

A comparison of dentifrices for clinical relief from dentin hypersensitivity using the Jay Sensitivity Sensor Probe.

PubMed

Hegde, Shashikanth; Rao, B H Sripathi; Kakar, Ravish Chander; Kakar, Ashish

2013-05-01

To evaluate the clinical relief from dentin hypersensitivity among subjects provided with a dentifrice formulated with 8% arginine, calcium carbonate and 1,000 ppm fluoride [sodium monofluorophosphate (MFP)] in comparison to those issued a commercially available dentifrice containing 1,000 ppm fluoride [as sodium monofluorophosphate (MFP)]. Clinical evaluations for hypersensitivity were performed with a novel tactile hypersensitivity measuring instrument--the Jay Sensitivity Sensor (Jay) Probe--in conjunction with evaporative triggers by air blast (Schiff scale) and Visual Analog Scores (VAS). Qualified adults from the Mangalore, India area who presented two teeth with dentin hypersensitivity were enrolled for this double-blind, randomized, parallel, controlled clinical trial conducted in an outpatient clinical setting. At baseline, dentin hypersensitivity was evaluated by the Jay Probe (tactile), air blast and VAS methods. Subjects were randomly issued a study dentifrice and instructed to brush their teeth for 1 minute twice daily with the provided dentifrice. Clinical evaluations for hypersensitivity were repeated after 2, 4 and 8 weeks of product use. 86 subjects (35 males and 51 females) complied with the study protocol and completed the entire study. At each recall visit, both treatment groups demonstrated significant reductions in dentin hypersensitivity from their corresponding baselines (P < 0.05). Subjects assigned the 8% arginine, calcium carbonate and 1,000 ppm fluoride dentifrice demonstrated statistically significant reductions in responses to tactile stimuli, air blast, and VAS responses in comparison to those using the dentifrice containing 1,000 ppm fluoride after 2, 4, and 8 weeks, respectively.

Development and pharmacological characterization of a model of sleep disruption-induced hypersensitivity in the rat.

PubMed

Wodarski, R; Schuh-Hofer, S; Yurek, D A; Wafford, K A; Gilmour, G; Treede, R-D; Kennedy, J D

2015-04-01

Sleep disturbance is a commonly reported co-morbidity in chronic pain patients, and conversely, disruption of sleep can cause acute and long-lasting hypersensitivity to painful stimuli. The underlying mechanisms of sleep disruption-induced pain hypersensitivity are poorly understood. Confounding factors of previous studies have been the sleep disruption protocols, such as the 'pedestal over water' or 'inverted flower pot' methods, that can cause large stress responses and therefore may significantly affect pain outcome measures. Sleep disruption was induced by placing rats for 8 h in a slowly rotating cylindrical cage causing arousal via the righting reflex. Mechanical (Von Frey filaments) and thermal (Hargreaves) nociceptive thresholds were assessed, and plasma corticosterone levels were measured (mass spectroscopy). Sleep disruption-induced hypersensitivity was pharmacologically characterized with drugs relevant for pain treatment, including gabapentin (30 mg/kg and 50 mg/kg), Ica-6p (Kv7.2/7.3 potassium channel opener; 10 mg/kg), ibuprofen (30 mg/kg and 100 mg/kg) and amitriptyline (10 mg/kg). Eight hours of sleep disruption caused robust mechanical and heat hypersensitivity in the absence of a measurable change in plasma corticosterone levels. Gabapentin had no effect on reduced nociceptive thresholds. Ibuprofen attenuated mechanical thresholds, while Ica-6p and amitriptyline attenuated only reduced thermal nociceptive thresholds. These results show that acute and low-stress sleep disruption causes mechanical and heat hypersensitivity in rats. Mechanical and heat hypersensitivity exhibited differential sensitivity to pharmacological agents, thus suggesting dissociable mechanisms for those two modalities. Ultimately, this model could help identify underlying mechanisms linking sleep disruption and hypersensitivity. © 2014 European Pain Federation - EFIC®

Management of hypersensitivity to platinum- and taxane-based chemotherapy: cepo review and clinical recommendations

PubMed Central

Boulanger, J.; Boursiquot, J.N.; Cournoyer, G.; Lemieux, J.; Masse, M.S.; Almanric, K.; Guay, M.P.

2014-01-01

Background Although antineoplastic agents are critical in the treatment of cancer, they can potentially cause hypersensitivity reactions that can have serious consequences. When such a reaction occurs, clinicians can either continue the treatment, at the risk of causing a severe or a potentially fatal anaphylactic reaction, or stop the treatment, although it might be the only one available. The objective of the present work was to evaluate the effectiveness of methods used to prevent and treat hypersensitivity reactions to platinum- or taxane-based chemotherapy and to develop evidence-based recommendations. Methods The scientific literature published to December 2013, inclusive, was reviewed. Results Premedication with antihistamines, H2 blockers, and corticosteroids is not effective in preventing hypersensitivity reactions to platinum salts. However, premedication significantly reduces the incidence of hypersensitivity to taxanes. A skin test can generally be performed to screen for patients at risk of developing a severe reaction to platinum salts in the presence of grade 1 or 2 reactions, but skin testing does not appear to be useful for taxanes. A desensitization protocol allows for re-administration of either platinum- or taxane-based chemotherapy to some patients without causing severe hypersensitivity reactions. Conclusions Several strategies such as premedication, skin testing, and desensitization protocols are available to potentially allow for administration of platinum- or taxane-based chemotherapy to patients who have had a hypersensitivity reaction and for whom no other treatment options are available. Considering the available evidence, the Comité de l’évolution des pratiques en oncologie made recommendations for clinical practice in Quebec. PMID:25089112

Telangiectatic Matting is Associated with Hypersensitivity and a Bleeding Tendency.

PubMed

Kadam, Pooja; Lim, Jerrick; Paver, Ian; Connor, David E; Parsi, Kurosh

2018-04-01

The aim was to investigate the pathogenesis of telangiectatic matting (TM) and identify possible risk factors. This study had two parts. The clinical records of consecutive patients were retrospectively analysed to identify risk factors for TM. In the second part, the haemostatic and coagulation profile of the subset of patients with TM were analysed and compared with controls using standard coagulation tests, platelet function and a global assay of coagulation (rotational thromboelastometry, ROTEM). In 352 consecutive patients presenting to a phlebology practice, 25 patients had TM (7.1%). All 25 patients were female with the median age of 45 (27-57) years. A comprehensive medical history was taken. Among 27 possible risk factors assessed, statistically significant associations included recurrent epistaxis, easy bruising, hypersensitivity (eczema, hives, hay fever, and rhinitis), previous treatment with sclerotherapy or endovenous laser for lower limb veins, and a family history of telangiectasias. Variables not associated with TM included oral contraceptive intake, hormone replacement therapy, and age. The haemostatic and coagulation profile of 12 patients (6 male and 6 female) with TM did not differ significantly from those without TM. TM is associated with both hypersensitivity and a bleeding tendency. This study revealed no significant increase in the incidence of haemostatic abnormalities in patients with TM compared with the control group. Given the significant association with hypersensitivity disorders, the underlying mast cell hyper-reactivity may contribute to both hypersensitivity and a bleeding tendency and predispose patients to TM. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Intestinal Membrane Permeability and Hypersensitivity In the Irritable Bowel Syndrome

PubMed Central

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

2009-01-01

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

Perceived food hypersensitivity relates to poor asthma control and quality of life in young non-atopic asthmatics.

PubMed

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

2015-01-01

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

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

PubMed

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

2014-12-30

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

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

PubMed Central

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

2014-01-01

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. PMID:25139411

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vogelius, Ivan S.; Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI; Department of Radiation Oncology, Rigshospitalet

2011-07-01

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

Clinical efficacy of a herbal dentifrice on dentinal hypersensitivity: a randomized controlled clinical trial.

PubMed

Kumari, M; Naik, S B; Rao, N S; Martande, S S; Pradeep, A R

2013-12-01

Dentinal hypersensitivity is a common problem and there is a growing interest in herbal based formulations for the treatment of oral diseases. This study was conducted to assess the efficacy of a commercially available novel herbal dentifrice in reduction of dentinal hypersensitivity. A total of 73 subjects (38 males and 35 females; aged 25-60 years) were randomly divided into two groups: Group 1 - a placebo dentifrice (The Himalaya Drug Company Research and Development, Makali, Bangalore) and Group 2 - (test group), a commercially available herbal dentifrice (Hi Ora K, The Himalaya Drug Company Research and Development, Makali, Bangalore). Sensitivity scores for controlled air stimulus and cold water were recorded at baseline, 6 weeks and 12 weeks. The test group was found to be significantly better compared to the placebo group at the end of 6 and 12 weeks in reduction of dentinal hypersensitivity. The novel herbal dentifrice can be recommended for treatment of dentinal hypersensitivity. © 2013 Australian Dental Association.

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

PubMed

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

2000-12-01

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

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�

[Anaphylaxis after vaccination due to hypersensitivity to gelatin].

PubMed

Kamin, W; Staubach, P; Klär-Hlawatsch, B; Erdnüss, F; Knuf, M

2006-01-01

Most allergic reactions after vaccination occur in patients sensitive to egg protein. Therefore this subject is well investigated, and the majority of common vaccines today contain only traces of egg protein. In contrast, there is little knowledge of hypersensitivities to other substances frequently contained in vaccines, e. g. antibiotics, phenol, gelatin and different preservatives. Here we report the case of a boy who had an anaphylactic reaction after being vaccinated against measles, mumps, rubella (MMR), and tick-born encephalitis (TBE) simultaneously. Different tests finally revealed a hypersensitivity to gelatin. This should be kept in mind especially during emergency care, since gelatin containing products like Haemaccel, Gelifundol or Gelofusin are widely used as colloid for resuscitation. If type 1 reactions after vaccination occur, gelatin should be taken into account as the causative agent. A medical alert card is recommended for such patients.

Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity

PubMed Central

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

2014-01-01

Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories. PMID:24707159

Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

PubMed

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

2014-04-07

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

Hypersensitivity reactions to HIV therapy

PubMed Central

Chaponda, Mas; Pirmohamed, Munir

2011-01-01

Many drugs used for the treatment of HIV disease (including the associated opportunistic infections) can cause drug hypersensitivity reactions, which vary in severity, clinical manifestations and frequency. These reactions are not only seen with the older compounds, but also with the newer more recently introduced drugs. The pathogenesis is unclear in most cases, but there is increasing evidence to support that many of these are mediated through a combination of immunologic and genetic factors through the major histocompatibility complex (MHC). Genetic predisposition to the occurrence of these allergic reactions has been shown for some of the drugs, notably abacavir hypersensitivity which is strongly associated with the class I MHC allele, HLA-B*5701. Testing before the prescription of abacavir has been shown to be of clinical utility, has resulted in a change in the drug label, is now recommended in clinical guidelines and is practiced in most Western countries. For most other drugs, however, there are no good methods of prevention, and clinical monitoring with appropriate (usually supportive and symptomatic) treatment is required. There is a need to undertake further research in this area to increase our understanding of the mechanisms, which may lead to better preventive strategies through the development of predictive genetic biomarkers or through guiding the design of drugs less likely to cause these types of adverse drug reactions. PMID:21480946

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

PubMed Central

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

2015-01-01

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

Spinal astrocyte gap junctions contribute to oxaliplatin-induced mechanical hypersensitivity.

PubMed

Yoon, Seo-Yeon; Robinson, Caleb R; Zhang, Haijun; Dougherty, Patrick M

2013-02-01

Spinal glial cells contribute to the development of many types of inflammatory and neuropathic pain. Here the contribution of spinal astrocytes and astrocyte gap junctions to oxaliplatin-induced mechanical hypersensitivity was explored. The expression of glial fibrillary acidic protein (GFAP) in spinal dorsal horn was significantly increased at day 7 but recovered at day 14 after oxaliplatin treatment, suggesting a transient activation of spinal astrocytes by chemotherapy. Astrocyte-specific gap junction protein connexin 43 (Cx43) was significantly increased in dorsal horn at both day 7 and day 14 following chemotherapy, but neuronal (connexin 36 [Cx36]) and oligodendrocyte (connexin 32 [Cx32]) gap junction proteins did not show any change. Blockade of astrocyte gap junction with carbenoxolone (CBX) prevented oxaliplatin-induced mechanical hypersensitivity in a dose-dependent manner and the increase of spinal GFAP expression, but had no effect once the mechanical hypersensitivity induced by oxaliplatin had fully developed. These results suggest that oxaliplatin chemotherapy induces the activation of spinal astrocytes and this is accompanied by increased expression of astrocyte-astrocyte gap junction connections via Cx43. These alterations in spinal astrocytes appear to contribute to the induction but not the maintenance of oxaliplatin-induced mechanical hypersensitivity. Combined, these results suggest that targeting spinal astrocyte/astrocyte-specific gap junction could be a new therapeutic strategy to prevent oxaliplatin-induced neuropathy. Spinal astrocytes but not microglia were recently shown to be recruited in paclitaxel-related chemoneuropathy. Here, spinal astrocyte gap junctions are shown to play an important role in the induction of oxaliplatin neuropathy. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

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

Usual interstitial pneumonia: typical, possible, and “inconsistent” patterns

PubMed Central

Torres, Pedro Paulo Teixeira e Silva; Rabahi, Marcelo Fouad; Moreira, Maria Auxiliadora Carmo; Meirelles, Gustavo de Souza Portes; Marchiori, Edson

2017-01-01

ABSTRACT Idiopathic pulmonary fibrosis is a severe and progressive chronic fibrosing interstitial lung disease, a definitive diagnosis being established by specific combinations of clinical, radiological, and pathological findings. According to current international guidelines, HRCT plays a key role in establishing a diagnosis of usual interstitial pneumonia (UIP). Current guidelines describe three UIP patterns based on HRCT findings: a typical UIP pattern; a pattern designated “possible UIP”; and a pattern designated “inconsistent with UIP”, each pattern having important diagnostic implications. A typical UIP pattern on HRCT is highly accurate for the presence of histopathological UIP, being currently considered to be diagnostic of UIP. The remaining patterns require further diagnostic investigation. Other known causes of a UIP pattern include drug-induced interstitial lung disease, chronic hypersensitivity pneumonitis, occupational diseases (e.g., asbestosis), and connective tissue diseases, all of which should be included in the clinical differential diagnosis. Given the importance of CT studies in establishing a diagnosis and the possibility of interobserver variability, the objective of this pictorial essay was to illustrate all three UIP patterns on HRCT. PMID:29160385

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.

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

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

ERIC Educational Resources Information Center

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

2017-01-01

Sensory hypersensitivity and insistence on sameness (I/S) are common, co-occurring features of autism, yet the relationship between them is poorly understood. This study assessed the impact of sensory hypersensitivity on the clinical symptoms of specific phobia, separation anxiety, social anxiety and I/S for autistic and typically developing (TD)…

Randomized clinical trial on the effect of a multispecies probiotic on visceroperception in hypersensitive IBS patients.

PubMed

Ludidi, S; Jonkers, D M; Koning, C J; Kruimel, J W; Mulder, L; van der Vaart, I B; Conchillo, J M; Masclee, A A M

2014-05-01

Irritable bowel syndrome (IBS) is characterized by heterogeneous pathophysiology and low response to treatment. Up to 60% of IBS patients suffers from visceral hypersensitivity, which is associated with symptom severity and underlying pathophysiological mechanisms. Recently, positive effects of probiotics in IBS have been reported, but overall the response was modest. We performed a study in IBS patients, characterized by visceral hypersensitivity measured with the rectal barostat, aiming to assess the effect of 6 weeks of multispecies probiotic mix on visceral pain perception. We conducted a randomized, placebo-controlled, double-blind trial in forty Rome III IBS patients with visceral hypersensitivity. Prior to intake, patients kept a 2-week symptom diary and underwent a rectal barostat measurement. When hypersensitivity was confirmed, participation was allowed and patients received a multispecies probiotic with in vitro proven potential beneficial effects on mechanisms contributing to visceral hypersensitivity (six different probiotic strains; 10(9)  cfu/g), or a placebo product of one sachet (5 g) per day for 6 weeks. At the end of the intervention period, visceroperception and symptoms were reassessed. Thirty-five patients completed the trial. The percentage of patients with visceral hypersensitivity decreased significantly in the probiotic and placebo group (76.5% and 71.4%, respectively; N.S. between groups). Improvement in pain scores and mean symptom score did not differ between the probiotic and placebo group. In this placebo-controlled trial in IBS patients with visceral hypersensitivity, no significant effect of a multispecies probiotic on viscerperception was observed. The study has been registered in the US National Library of Medicine (http://www.clinicaltrials.gov, NCT00702026). © 2014 John Wiley & Sons Ltd.

Protection from radiation-induced pneumonitis using cerium oxide nanoparticles.

PubMed

Colon, Jimmie; Herrera, Luis; Smith, Joshua; Patil, Swanand; Komanski, Chris; Kupelian, Patrick; Seal, Sudipta; Jenkins, D Wayne; Baker, Cheryl H

2009-06-01

In an effort to combat the harmful effects of radiation exposure, we propose that rare-earth cerium oxide (CeO(2)) nanoparticles (free-radical scavengers) protect normal tissue from radiation-induced damage. Preliminary studies suggest that these nanoparticles may be a therapeutic regenerative nanomedicine that will scavenge reactive oxygen species, which are responsible for radiation-induced cell damage. The effectiveness of CeO(2) nanoparticles in radiation protection in murine models during high-dose radiation exposure is investigated, with the ultimate goal of offering a new approach to radiation protection, using nanotechnology. We show that CeO(2) nanoparticles are well tolerated by live animals, and they prevent the onset of radiation-induced pneumonitis when delivered to live animals exposed to high doses of radiation. In the end, these studies provide a tremendous potential for radioprotection and can lead to significant benefits for the preservation of human health and the quality of life for humans receiving radiation therapy.

Immediate hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines: reports to VAERS.

PubMed

Halsey, Neal A; Griffioen, Mari; Dreskin, Stephen C; Dekker, Cornelia L; Wood, Robert; Sharma, Devindra; Jones, James F; LaRussa, Philip S; Garner, Jenny; Berger, Melvin; Proveaux, Tina; Vellozzi, Claudia; Broder, Karen; Setse, Rosanna; Pahud, Barbara; Hrncir, David; Choi, Howard; Sparks, Robert; Williams, Sarah Elizabeth; Engler, Renata J; Gidudu, Jane; Baxter, Roger; Klein, Nicola; Edwards, Kathryn; Cano, Maria; Kelso, John M

2013-12-09

Hypersensitivity disorders following vaccinations are a cause for concern. To determine the type and rate by age, gender, and vaccine received for reported hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines. A systematic review of reports to the Vaccine Adverse Event Reporting System (VAERS) following monovalent 2009 pandemic influenza A (H1N1) vaccines. US Civilian reports following vaccine received from October 1, 2009 through May 31, 2010. Age, gender, vaccines received, diagnoses, clinical signs, and treatment were reviewed by nurses and physicians with expertise in vaccine adverse events. A panel of experts, including seven allergists reviewed complex illnesses and those with conflicting evidence for classification of the event. Of 1984 reports, 1286 were consistent with immediate hypersensitivity disorders and 698 were attributed to anxiety reactions, syncope, or other illnesses. The female-to-male ratio was ≥4:1 for persons 20-to-59 years of age, but approximately equal for children under 10. One hundred eleven reports met Brighton Collaboration criteria for anaphylaxis; only one-half received epinephrine for initial therapy. The overall rate of reported hypersensitivity reactions was 10.7 per million vaccine doses distributed, with a 2-fold higher rate for live vaccine. Underreporting, especially of mild events, would result in an underestimate of the true rate of immediate hypersensitivity reactions. Selective reporting of events in adult females could have resulted in higher rates than reported for males. Adult females may be at higher risk of hypersensitivity reactions after influenza vaccination than men. Although the risk of hypersensitivity reactions following 2009 pandemic influenza A (H1N1) vaccines was low, all clinics administering vaccines should be familiar with treatment guidelines for these adverse events, including the use of intramuscular epinephrine early in the course of serious hypersensitivity

Intraluminal fibrosis in interstitial lung disorders.

PubMed Central

Basset, F.; Ferrans, V. J.; Soler, P.; Takemura, T.; Fukuda, Y.; Crystal, R. G.

1986-01-01

The histopathologic and ultrastructural features of intraluminal organizing and fibrotic changes were studied in open lung biopsies and autopsy specimens from 373 patients with interstitial lung disorders, including hypersensitivity pneumonitis (n = 44), idiopathic pulmonary fibrosis (n = 92), collagen-vascular diseases (n = 20), chronic eosinophilic pneumonia (n = 10), pulmonary histiocytosis X (n-90), pulmonary sarcoidosis (n = 62), pneumoconioses (n = 25), Legionnaire's disease (n = 5), drug- and toxin-induced pneumonitis (n = 4), radiation-induced pneumonitis (n = 2), lymphangioleiomyomatosis (n = 11), and chronic organizing pneumonia of unknown cause (n = 8). Three patterns of intraluminal organization and fibrosis were recognized: 1) intraluminal buds, which partially filled the alveoli, alveolar ducts and/or distal bronchioles; 2) obliterative changes, in which loose connective tissue masses obliterated the lumens of alveoli, alveolar ducts or distal bronchioles, and 3) mural incorporation of previously intraluminal connective tissue masses, which fused with alveolar, alveolar ductal, or bronchiolar structures and frequently became reepithelialized. All three patterns had common morphologic features, suggesting that, regardless of their severity, they resulted from a common pathogenetic mechanism, ie, the migration of activated connective tissue cells, through defects in the epithelial lining and its basement membrane, from the interstitial into the intraluminal compartment. Intraluminal buds were observed most frequently in hypersensitivity pneumonitis, chronic eosinophilic pneumonia, and organizing pneumonia of unknown cause. Mural incorporation and, to a lesser extent, obliterative changes were observed in most interstitial disorders and were very prominent in idiopathic pulmonary fibrosis. Mural incorporation and obliterative changes play an important role in pulmonary remodeling, especially when several adjacent alveoli and/or other air spaces are

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

Moldy buildings, health of their occupants and fungal prevention.

PubMed

Mihinova, D; Pieckova, E

2012-01-01

Microscopic fungi are important biological pollutants in the indoor environment, they are spread generally: on building materials, carpets, ceiling tiles, insulations, any surfaces, wallpapers, or in heating, ventilation, and air conditioning systems. Molds are able to grow on any materials, as long as moisture and oxygen are available. Exposure to fungi in indoor environments (esp. in water-damaged buildings) can cause adverse health effects, such as allergy, asthma, hypersensitivity pneumonia, mucous membrane irritation, different toxic effects, or even mycoses (in immunocompromised individuals) - alone or in combination. As serious adverse health effects could be caused antifungal prevention is an absolute need.This review article summarizes the occurrence of fungi in the indoor environment of buildings and their contribution to occupants´ health problems, and preventive measures against molds (Tab. 1, Fig. 1, Ref. 48).

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.

Inhibition by Agrobacterium tumefaciens and Pseudomonas savastanoi of development of the hypersensitive response elicited by Pseudomonas syringae pv. phaseolicola.

PubMed Central

Robinette, D; Matthysse, A G

1990-01-01

Injection into tobacco leaves of biotype 1 Agrobacterium tumefaciens or of Pseudomonas savastanoi inhibited the development of a visible hypersensitive response to the subsequent injection at the same site of Pseudomonas syringae pv. phaseolicola. This interference with the hypersensitive response was not seen with injection of bacterial growth medium or Escherichia coli cells. Live A. tumefaciens cells were required for the inhibitory effect. Various mutants and strains of A. tumefaciens were examined to determine the genes involved. Known chromosomal mutations generally had no effect on the ability of A. tumefaciens to inhibit the hypersensitive response, except for chvB mutants which showed a reduced (but still significant) inhibition of the hypersensitive response. Ti plasmid genes appeared to be required for the inhibition of the hypersensitive response. The bacteria did not need to be virulent in order to inhibit the hypersensitive response. Deletion of the vir region from pTi had no effect on the inhibition. However, the T region of the Ti plasmid was required for inhibition. Studies of transposon mutants suggested that the tms but not tmr or ocs genes were required. These genes were not acting after transfer to plant cells since they were effective in strains lacking vir genes and thus unable to transfer DNA to plant cells. The results suggest that the expression of the tms genes in the bacteria may inhibit the development of the hypersensitive response by the plant. An examination of the genes required in P. savastanoi for the inhibition of the hypersensitive response suggested that bacterial production of auxin was also required for the inhibition of the hypersensitive response by these bacteria. Images PMID:2211508

The role of skin barrier in occupational contact dermatitis.

PubMed

Jakasa, Ivone; Thyssen, Jacob P; Kezic, Sanja

2018-06-12

Skin diseases represent one of the most common work-related diseases and may have a detrimental effect on social, personal and occupational aspects of life. Contact dermatitis, which comprises predominately irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) accounts for vast majority of occupational skin diseases, especially in occupations associated with frequent skin contact with irritants and contact allergens. Although ICD and ACD have similar clinical manifestation, their pathophysiology and the role of the skin barrier is different. In ICD, perturbation of the skin barrier is the primary event which sets into motion diverse metabolic processes and triggers activation of innate immunity without involvement of adaptive immune system. In ACD, a type IV hypersensitivity reaction induced by contact allergens, the skin barrier impairment may evoke innate signaling pathways during the sensitization phase required for the activation of T-cell adaptive response. Thus, skin barrier impairment may increase the risk of ICD or ACD not only because of enhanced permeability and ingress of irritants and allergens, but also by generation of innate immune signal needed for the induction of allergic response. Hence, an efficient way to prevent CD is to avoid skin barrier damage in the workplace. This review focuses on the skin barrier, how it is affected by skin irritants and how its impairment contributes to development of ICD and ACD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Desensitization to ceftaroline in a patient with multiple medication hypersensitivity reactions.

PubMed

Jones, Justin M; Richter, Lisa M; Alonto, Augusto; Leedahl, David D

2015-02-01

The case of a patient with multiple medication hypersensitivity reactions and a methicillin-resistant Staphylococcus aureus (MRSA) infection who underwent desensitization to ceftaroline is reported. A 32-year-old Caucasian woman with asthma, gastroesophageal reflux disease, heart murmur, and major depression was admitted for MRSA cellulitis with a subcutaneous abscess along the left sternomanubrial joint and clavicular osteomyelitis secondary to port placement after gastric bypass surgery. The patient had an extensive history of hypersensitivity reactions. Pertinent documented allergies were as follows: penicillin (anaphylaxis), daptomycin (anaphylaxis), vancomycin (hives), linezolid (hives), ertapenem (rash), ciprofloxacin (rash), and tigecycline (rash). The patient also reported previous reactions to aztreonam (unknown) and gentamicin (hives). The pharmacy was consulted to develop a desensitization protocol for ceftaroline. The desensitization protocol used three serial dilutions of ceftaroline to make 14 sequential infusions with escalating doses. Intramuscular epinephrine, i.v. diphenhydramine, and i.v. methylprednisolone were ordered as needed for the development of immediate hypersensitivity reactions during or after administration of ceftaroline. The cumulative dose (574.94 mg) was administered intravenously over 225 minutes with no breakthrough symptoms reported during or after the desensitization protocol. Ceftaroline fosamil 600 mg i.v. every 12 hours was continued for six weeks. Desensitization to ceftaroline was conducted for a patient with extensive history of hypersensitivity reactions to other drugs, including penicillin-induced anaphylaxis. Desensitization and subsequent treatment with full doses of ceftaroline were accomplished without apparent adverse effects. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Calcium-mediated apoptosis in a plant hypersensitive disease resistance response.

PubMed

Levine, A; Pennell, R I; Alvarez, M E; Palmer, R; Lamb, C

1996-04-01

Avirulent pathogens elicit a battery of plant defenses, often accompanied by collapse of the challenged cells. In soybean cells, sustained accumulation of H2O2 from an oxidative burst cues localized host cell death. Such hypersensitive cell death appears to be an active process, but little is known about the mechanisms underlying cellular collapse. We show that H2O2 stimulates a rapid influx of Ca2+ into soybean cells, which activates a physiological cell death program resulting in the generation of large (approximately 50 kb) DNA fragments and cell corpse morphology--including cell shrinkage, plasma membrane blebbing and nuclear condensation--characteristic of apoptosis. In contrast, H2O2 induction of the cellular protectant gene glutathione S-transferase is Ca(2+)-independent. Apoptosis in soybean cells and leaf tissue was induced by avirulent Pseudomonas syringae pv. glycinea but was not observed at comparable stages of the compatible interaction with the isogenic virulent strain, which fails to elicit a hypersensitive response. Apoptosis was also observed at the onset of the hypersensitive response in Arabidopsis leaves inoculated with avirulent P. syringae pv. tomato and in tobacco cells treated with the fungal peptide cryptogein, which is involved in the induction of non-host resistance to Phytophthora cryptogea. These observations establish a signal function for Ca2+ downstream of the oxidative burst in the activation of a physiological cell death program in soybean cells that is similar to apoptosis in animals. That the characteristic cell corpse morphology is also induced in Arabidopsis and tobacco by different avirulence signals suggests that apoptosis may prove to be a common, but not necessarily ubiquitous, feature of incompatible plant-pathogen interactions. Emerging similarities between facets of hypersensitive disease resistance and the mammalian native immune system indicate that apoptosis is a widespread defence mechanism in eukaryotes.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-01

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

Self-reported prevalence of hypersensitivity reactions against drugs among medical students: does awareness cause any difference?

PubMed

Bavbek, Sevim; Erkekol, Ferda Öner; Celik, Gülfem Elif; Gönüllü, Ipek; Misirligil, Zeynep

2011-02-01

True epidemiologic data on hypersensitivity reactions to drugs are scarce. More accurate data may be obtained in more specific clinical settings. Considering their educational background, medical students may be an appropriate target audience for evaluating prevalence of drug hypersensitivity. This study is designed to determine the prevalence of self-reported drug hypersensitivity alongside related factors among young adults. A structured questionnaire was administered to the students. A total of 1267 students (mean age: 21.71+1.90 years, F/M: 648/619) from all grades responded to the survey. The mean prevalence of self-reported drug hypersensitivity was 4.7% (60/1267). The most frequently involved drugs were beta-lactam antibiotics (55%) followed by non-steroidal anti-inflammatory drugs (28%). The most commonly reported clinical presentations were cutaneous (43.3%), followed by systemic (36.8%), cardiovascular (8.3%) and respiratory (8.3%) symptoms. Factors related with reported reactions were higher grades (p=0.015, OR: 2.09), female gender (p=0.006, OR: 2.13), personal history of allergic diseases (p=0.001, OR: 2.64), and family history of drug hypersensitivity (p<0.001, OR: 5.78). Half of the students sought medical help during the acute stage of their reaction. Only 3.2% of the cases have been referred to an allergist for further evaluation. This study, the first of its kind in Turkey, with medical students showed that self-reported hypersensitivity reactions to drugs is highly prevalent and its prevalence seems to be affected by awareness of the individuals in addition to previously reported risk factors. The education of both patients and physicians on the management of drug hypersensitivity seems to be necessary. Copyright © 2010 John Wiley & Sons, Ltd.

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. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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.

Investigation of Seminal Plasma Hypersensitivity Reactions

DTIC Science & Technology

1998-10-01

the same questionnaire which has been used to screen civilian populations of women with localized and/or systemic seminal plasma hypersensitivity. This...3. If not, how many times have you experienced a reaction with other sexual partners? 4. Did you have the reaction on your first intercourse? A...YES B. NO 5. 6. If the answer above is no, how many years after your first intercourse did the firstreaction occur? Prior to the

Hypersensitivity reaction to mizolastine: study of cross reactions.

PubMed

Gonzalo-Garijo, M A; Jiménez-Ferrera, G; Bobadilla-González, P; Cordobés-Durán, C

2006-01-01

A 26-year-old male suffering from acute rhinitis took the first dose of Zolistan (mizolastine, 10 mg), orally, and 15 minutes later he developed intense generalized pruritus, cutaneous rash, oropharyngeal pruritus, edema on his face, difficulty in swallowing, and mild dyspnea. He was treated with methylprednisolone and epinephrine and improved within 30 minutes. The patient had not taken mizolastine before and he has avoided it since the reaction. Cutaneous tests with Zolistan and its excipients proved negative. Simple-blind oral challenge tests with the excipients and then with Zolistan were positive only with Zolistan. In order to confirm the absence of cross-reactivity between mizolastine and other benzimidazoles, we tested omeprazole, domperidone and mebendazole, all of which yielded negative results. To our knowledge, this is the second case of immediate hypersensitivity to mizolastine documented to date. In our case, the clinical history, physical examination and provocation tests allow us to establish the diagnosis of hypersensitivity to mizolastine and exclude the cross reactivity with other benzimidazole derivatives.

Absence of cellular hypersensitivity to muscle and thymic antigens in myasthenia gravis.

PubMed Central

Behan, W M; Behan, P O; Simpson, J A

1975-01-01

Humoral antibodies to skeletal muscle and its components and to thymus have been demonstrated in the sera of patients with myasthenia gravis. A role for cellular hypersensitivity to similar antigens in the pathogenesis of the disease has been suggested by some reports of the presence of cellular immunity. A detailed immunological study using muscle and thymic antigens, including those prepared from the patients' own tissues, failed to confirm these findings. It is suggested that previous reports of cellular hypersensitivity represent the demonstration of an epiphenomenon. PMID:1206412

Immediate-type hypersensitivity reaction to Mannitol as drug excipient (E421): a case report.

PubMed

Calogiuri, G F; Muratore, L; Nettis, E; Casto, A M; Di Leo, E; Vacca, A

2015-05-01

Allergic reactions to mannitol have been reported rarely, despite its widespread use as a drug and as a food excipient. This is the first case report in which oral mannitol induces an immediate type hypersensitivity as a drug excipient, in a 42 year old man affected by rhinitis to olive tree pollen. Unusual and undervalued risk factors for mannitol hypersensitivity are examined.

Comparison of two different forms of varnishes in the treatment of dentine hypersensitivity: a subject-blind randomised clinical study.

PubMed

Sethna, Gulnar Dara; Prabhuji, M L V; Karthikeyan, B V

2011-01-01

Dentine hypersensitivity is one of the most frequently recorded complaints of dental discomfort. Current evidence implicates patent dentinal tubules in hypersensitive dentine, and it follows that one effective way to reduce dentine sensitivity is to occlude the dentinal tubules. The purpose of this study was to compare the efficacy of two different desensitising agents, Cervitec varnish and Gluma varnish. Two hundred fifty patients self-reporting dentine hypersensitivity completed the paired split mouth randomised, subject-blind study. Each participant had a minimum of two sensitive teeth in at least two different quadrants and displaying a response of ≥3 cm to an evaporative stimulus. The hypersensitivity levels were measured with a tactile stimulus (scratchometer), thermal stimulus (cold water test), and an evaporative stimulus (air blast test) using a visual analogue scale. The teeth were evaluated immediately after treatment, and at 4 and 12 weeks after application of the chlorhexidine-containing varnish Cervitec and the glutaraldehyde-containing varnish, Gluma Desensitizer. Statistical analysis indicated that both the desensitising varnishes were effective in alleviating dentine hypersensitivity at all time intervals compared to baseline. There was a highly statistically significantly greater reduction in dentine hypersensitivity to evaporative stimulus, cold stimulus, and tactile stimulus after application of Cervitec than after Gluma Desensitizer (P < 0.001). Both the varnishes have a therapeutic potential to alleviate dentine hypersensitivity at all time intervals compared to baseline. However, Cervitec varnish is more efficacious in reducing dentine hypersensitivity than Gluma varnish at both 4 weeks and 12 weeks post-treatment.

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

Suspected zonisamide-related anticonvulsant hypersensitivity syndrome in a cat.

PubMed

Collinet, Audrey; Sammut, Veronique

2017-12-15

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

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

Effect of Rap1 binding on DNA distortion and potassium permanganate hypersensitivity.

PubMed

Le Bihan, Yann-Vaï; Matot, Béatrice; Pietrement, Olivier; Giraud-Panis, Marie-Josèphe; Gasparini, Sylvaine; Le Cam, Eric; Gilson, Eric; Sclavi, Bianca; Miron, Simona; Le Du, Marie-Hélène

2013-03-01

Repressor activator protein 1 (Rap1) is an essential factor involved in transcription and telomere stability in the budding yeast Saccharomyces cerevisiae. Its interaction with DNA causes hypersensitivity to potassium permanganate, suggesting local DNA melting and/or distortion. In this study, various Rap1-DNA crystal forms were obtained using specifically designed crystal screens. Analysis of the DNA conformation showed that its distortion was not sufficient to explain the permanganate reactivity. However, anomalous data collected at the Mn edge using a Rap1-DNA crystal soaked in potassium permanganate solution indicated that the DNA conformation in the crystal was compatible with interaction with permanganate ions. Sequence-conservation analysis revealed that double-Myb-containing Rap1 proteins all carry a fully conserved Arg580 at a position that may favour interaction with permanganate ions, although it is not involved in the hypersensitive cytosine distortion. Permanganate reactivity assays with wild-type Rap1 and the Rap1[R580A] mutant demonstrated that Arg580 is essential for hypersensitivity. AFM experiments showed that wild-type Rap1 and the Rap1[R580A] mutant interact with DNA over 16 successive binding sites, leading to local DNA stiffening but not to accumulation of the observed local distortion. Therefore, Rap1 may cause permanganate hypersensitivity of DNA by forming a pocket between the reactive cytosine and Arg580, driving the permanganate ion towards the C5-C6 bond of the cytosine.

Natural history of perceived food hypersensitivity and IgE sensitisation to food allergens in a cohort of adults.

PubMed

Patelis, Antonios; Gunnbjörnsdottir, Maria; Borres, Magnus P; Burney, Peter; Gislason, Thorarinn; Torén, Kjell; Forsberg, Bertil; Alving, Kjell; Malinovschi, Andrei; Janson, Christer

2014-01-01

No longitudinal studies exist on the natural history of food hypersensitivity and IgE sensitisation to food allergens in adults. To examine the natural history of food hypersensitivity, the natural history of IgE sensitisation to food allergens and to investigate the risk factors for new onset food hypersensitivity. Food hypersensitivity was questionnaire-assessed in 2307 individuals (aged 20-45 years) from Iceland and Sweden during the European Community Respiratory Health Survey both at baseline and follow-up 9 years later. IgE food and aeroallergen sensitisation were assessed in a subgroup of these individuals (n = 807). Values of 0.35 kU/L and above were regarded as positive sensitisation. Food hypersensitivity was reported by 21% of the subjects and this proportion remained unchanged at follow-up (p = 0.58). Fruits, nuts and vegetables were the three most common causes of food hypersensitivity, with a similar prevalence at baseline and follow-up. The prevalence IgE sensitisation to food allergens decreased in general by 56% (p<0.001) and IgE sensitisation to peanut decreased in particular by 67% (p = 0.003). The prevalence of timothy grass IgE sensitisation decreased by 15% (p = 0.003) while cat, mite and birch IgE sensitisation did not decrease significantly. Female sex, rhinitis, eczema and presence of IgE sensitisation to aeroallergens were independently associated with new onset food hypersensitivity. The prevalence of food hypersensitivity remained unchanged while the prevalence of IgE sensitisation to food allergens decreased in adults over a 9-year follow-up period. The decrease in prevalence of IgE sensitisation to food allergens was considerably larger than the change in prevalence of IgE sensitisation to aeroallergens.

Natural History of Perceived Food Hypersensitivity and IgE Sensitisation to Food Allergens in a Cohort of Adults

PubMed Central

Patelis, Antonios; Gunnbjörnsdottir, Maria; Borres, Magnus P.; Burney, Peter; Gislason, Thorarinn; Torén, Kjell; Forsberg, Bertil; Alving, Kjell

2014-01-01

Background No longitudinal studies exist on the natural history of food hypersensitivity and IgE sensitisation to food allergens in adults. Objective To examine the natural history of food hypersensitivity, the natural history of IgE sensitisation to food allergens and to investigate the risk factors for new onset food hypersensitivity. Methods Food hypersensitivity was questionnaire-assessed in 2307 individuals (aged 20–45 years) from Iceland and Sweden during the European Community Respiratory Health Survey both at baseline and follow-up 9 years later. IgE food and aeroallergen sensitisation were assessed in a subgroup of these individuals (n = 807). Values of 0.35 kU/L and above were regarded as positive sensitisation. Results Food hypersensitivity was reported by 21% of the subjects and this proportion remained unchanged at follow-up (p = 0.58). Fruits, nuts and vegetables were the three most common causes of food hypersensitivity, with a similar prevalence at baseline and follow-up. The prevalence IgE sensitisation to food allergens decreased in general by 56% (p<0.001) and IgE sensitisation to peanut decreased in particular by 67% (p = 0.003). The prevalence of timothy grass IgE sensitisation decreased by 15% (p = 0.003) while cat, mite and birch IgE sensitisation did not decrease significantly. Female sex, rhinitis, eczema and presence of IgE sensitisation to aeroallergens were independently associated with new onset food hypersensitivity. Conclusion The prevalence of food hypersensitivity remained unchanged while the prevalence of IgE sensitisation to food allergens decreased in adults over a 9-year follow-up period. The decrease in prevalence of IgE sensitisation to food allergens was considerably larger than the change in prevalence of IgE sensitisation to aeroallergens. PMID:24427301

Clinical Correlates of Carbon Dioxide Hypersensitivity in Children.

PubMed

Rappaport, Lance M; Sheerin, Christina; Carney, Dever M; Towbin, Kenneth E; Leibenluft, Ellen; Pine, Daniel S; Brotman, Melissa A; Roberson-Nay, Roxann; Hettema, John M

2017-12-01

Hypersensitivity to carbon dioxide (CO 2 )-enriched air may be a promising risk marker for anxiety disorders. Among adult and adolescent samples, heterogeneity in distress response to the CO 2 challenge task indexes 3 underlying classes of individuals, which distinguish between sustained and acute threat response as markers for internalizing disorders, broadly, and anxiety disorders, specifically. The present study examines latent classes in children's response to the CO 2 challenge task to clarify the association of CO 2 hypersensitivity with anxiety and internalizing symptomatology in childhood. Healthy children from a community twin sample (N = 538; age 9-13 years) rated anxious distress every 2 minutes while breathing air enriched to 7.5% CO 2 for 8 minutes. Latent growth mixture modeling evaluated potential classes of individuals with characteristic trajectories of distress during the task to clarify the association with internalizing disorder symptoms and related traits (e.g., anxiety sensitivity, irritability). Although all participants reported increased distress during the task, interindividual heterogeneity in distress indexed 3 underlying classes: a consistently low class ("low"), a consistently high class ("high"), and participants who demonstrated markedly increased acute distress ("acute"). Compared to the low class, the high class reported greater internalizing psychopathology, whereas membership in the acute class was associated with experiencing a panic-like event during the task. As in older individuals, 3 distinct trajectories emerged to capture interindividual heterogeneity in children's distress during the CO 2 challenge task. These classes were distinguished by clinical validators that reinforce the association of CO 2 hypersensitivity and internalizing disorder phenotypes in children. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. All rights reserved.

Pharmacological evaluation of NSAID-induced gastropathy as a "Translatable" model of referred visceral hypersensitivity.

PubMed

Hummel, Michele; Knappenberger, Terri; Reilly, Meghan; Whiteside, Garth T

2017-09-07

To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice ( n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential (TRP), sodium and acid-sensing ion channels (ASICs) as well as opioid receptors and guanylate cyclase C (GC-C). Results showed that two opioids and a GC-C agonist, morphine, asimadoline and linaclotide, respectively, the TRP antagonists, AMG9810 and HC-030031 and the sodium channel blocker, carbamazepine, elicited a dose- and/or time-dependent attenuation of referred visceral hypersensitivity, while the ASIC blocker, amiloride, was ineffective at all doses tested. Together, these findings implicate opioid receptors, GC-C, and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly, these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties.

Pharmacological evaluation of NSAID-induced gastropathy as a "Translatable" model of referred visceral hypersensitivity

PubMed Central

Hummel, Michele; Knappenberger, Terri; Reilly, Meghan; Whiteside, Garth T

2017-01-01

AIM To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. METHODS Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice (n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential (TRP), sodium and acid-sensing ion channels (ASICs) as well as opioid receptors and guanylate cyclase C (GC-C). RESULTS Results showed that two opioids and a GC-C agonist, morphine, asimadoline and linaclotide, respectively, the TRP antagonists, AMG9810 and HC-030031 and the sodium channel blocker, carbamazepine, elicited a dose- and/or time-dependent attenuation of referred visceral hypersensitivity, while the ASIC blocker, amiloride, was ineffective at all doses tested. CONCLUSION Together, these findings implicate opioid receptors, GC-C, and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly, these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties. PMID:28970722

Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain

PubMed Central

Liu, Da-Lu; Lu, Na; Han, Wen-Juan; Chen, Rong-Gui; Cong, Rui; Xie, Rou-Gang; Zhang, Yu-Fei; Kong, Wei-Wei; Hu, San-Jue; Luo, Ceng

2015-01-01

Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron’s ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensitivity. Amongst nociceptive DRG neurons, a mechanically sensitive neuron, isolectin B4 negative Aδ-type (IB4− Aδ) DRG neuron displays spontaneous activity with hyperexcitability after chronic compression of cervical DRGs. Focal mechanical stimulation on somata of IB4- Aδ neuron induces abnormal hypersensitivity. Upregulated HCN1 and HCN3 channels and increased Ih current on this subset of primary nociceptors underlies the spontaneous activity together with neuronal mechanical hypersensitivity, which further contributes to the behavioral mechanical hypersensitivity associated with CRP. This study sheds new light on the functional plasticity of a specific subset of nociceptive DRG neurons to mechanical stimulation and reveals a novel mechanism that could underlie the mechanical hypersensitivity associated with cervical radiculopathy. PMID:26577374

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.

Microbiological agents as health risks in indoor air.

PubMed Central

Burrell, R

1991-01-01

Ambient air may be contaminated with or carry significant levels of a variety of potentially harmful microorganisms. There are three major sources of such microbes: a) those arising from microbial decomposition of various substrates associated with particular occupations (e.g., "moldy" hay leading to hypersensitivity pneumonitis), b) those associated with certain types of environments (e.g., Legionnaires' bacteria in water supplies), and c) those stemming from infective individuals harboring a particular pathogen (e.g., tuberculosis). This presentation deals primarily with important microorganisms from occupational and environmental sources and clearly differentiates from case to case transmission via droplet nuclei infection. Microorganisms that are uniformly injurious are differentiated from those that are more opportunistic (i.e., those that cause problems only in people with preexisting debilities). Such microorganisms are categorized according to whether they are allergenic, infectious, or capable of inducing toxic or inflammatory reactions when inhaled. Representative examples from each of these categories, which include bacteria, fungi, rickettsia, and amoebae, are discussed. The conditions responsible for the entrance of significant numbers of these microbes into the air, the mechanisms by which they produce injury, and the methods of prevention are also considered. With attention given to some of the basic sources and requirements for such microorganisms to reproduce and enter the ambient air environment, it is a relatively simple matter to prevent the occurrence of health problems. PMID:1669959

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

PubMed

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

2015-12-01

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

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

PubMed Central

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

2015-01-01

Many pathogens usurp the host hemostatic system during infection to promote pathogenesis. Yersinia pestis, the causative agent of plague, expresses the plasminogen activator protease Pla, which has been shown in vitro to target and cleave multiple proteins within the fibrinolytic pathway, including the plasmin inhibitor α2-antiplasmin (A2AP). It is not known, however, if Pla inactivates A2AP in vivo; the role of A2AP during respiratory Y. pestis infection is not known either. Here, we show that Y. pestis does not appreciably cleave A2AP in a Pla-dependent manner in the lungs during experimental pneumonic plague. Furthermore, following intranasal infection with Y. pestis, A2AP-deficient mice exhibit no difference in survival time, bacterial burden in the lungs, or dissemination from wild-type mice. Instead, we found that in the absence of Pla, A2AP contributes to the control of the pulmonary inflammatory response during infection by reducing neutrophil recruitment and cytokine production, resulting in altered immunopathology of the lungs compared to A2AP-deficient mice. Thus, our data demonstrate that A2AP is not significantly affected by the Pla protease during pneumonic plague, and although A2AP participates in immune modulation in the lungs, it has limited impact on the course or ultimate outcome of the infection. PMID:26438794

Anisakis hypersensitivity in Italy: prevalence and clinical features: a multicenter study.

PubMed

2011-12-01

Anisakis simplex (As), a parasite in fish, is able to sensitize humans via the alimentary tract. The prevalence of hypersensitivity and allergy to As outside the Iberian peninsula has not been investigated so far. We investigated Anisakis hypersensitivity in different areas of Italy. Consecutive subjects seen at 34 Italian allergy centers from October to December 2010 were investigated both by specific interview and by skin prick test (SPT) with As extract. A total of 10 570 subjects were screened, of which 474 (4.5%) scored positive on Anisakis SPT and 66 of these (14% of those sensitized; 0.6% of the studied population) had a history of As allergy. Marinated anchovies were the most frequent cause of allergic reactions. Thirty-four (52%) patients were mono-sensitized to Anisakis. Sensitization rate showed marked geographic differences (range: 0.4-12.7%), being highest along the Adriatic and Tyrrhenian coasts, where homemade marinated anchovies are an age-old tradition. In inland centers in northern Italy, the prevalence was directly related to the number of inhabitants. The analysis of the impact of immigration on the prevalence of Anisakis hypersensitivity showed that about 60% of sensitized subjects in Milano and Torino came from southern Italy or from non-European countries. Anisakis hypersensitivity and allergy are mainly a matter of dietary habits. Areas where marinated anchovies are popular can be considered as 'endemic' for this type of food allergy, whereas immigration and, possibly, new or imported trendy food styles, such as eating raw fish carpaccios or sushi, are a major causative factor in big cities of inland zones. © 2011 John Wiley & Sons A/S.

Giardia duodenalis induces paracellular bacterial translocation and causes postinfectious visceral hypersensitivity

PubMed Central

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

2016-01-01

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

Auditory Hypersensitivity in Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Lucker, Jay R.

2013-01-01

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

Condition-specific role of colonic inflammatory molecules in persistent functional colorectal hypersensitivity in the mouse

PubMed Central

La, Jun-Ho; Gebhart, G. F.

2014-01-01

Background A low-level inflammation has been hypothesized to mediate visceral hypersensitivity in functional bowel disorders that persist after or even in the absence of gut inflammation. We aimed to test the efficacy of a steroidal anti-inflammatory treatment, and identify local inflammatory molecules mediating post- and non-inflammatory colorectal hypersensitivity using two mouse models. Methods Visceromotor responses to colorectal distension were quantified as a measure of colorectal sensitivity. On day 1, mice received intracolonic saline (control), trinitrobenzenesulfonic acid (post-inflammatory on day 15), or acidified hypertonic saline (non-inflammatory). Colorectal sensitivity before (day 10) and after (day 15) four-day dexamethasone treatment was compared, and colonic gene expression of inflammatory molecules was quantified. Results Dexamethasone effectively inhibited gene expression of inflammatory molecules such as interleukin (IL)-1β and mast cell protease-1 in the colon, but did not attenuate colorectal hypersensitivity in either model. Gene expression of inflammatory molecules in the colon did not differ between control and the non-inflammatory model, but the post-inflammatory model showed increased IL-10 and tight junction protein 2, and decreased IL-6, transforming growth factor (TGF)-β, a precursor of β-endorphin, occludin, and mucin 2. While no common molecule explained colorectal hypersensitivity in these models, hypersensitivity was positively correlated with TGF-β2 mRNA in control, and with IL-1β, inhibin βA and prostaglandin E2 synthase in the dexamethasone-treated post-inflammatory model. In the non-inflammatory model, cyclooxygenase-2 mRNA was negatively correlated with colorectal sensitivity. Conclusion These results suggest that persistent functional colorectal hypersensitivity is mediated by condition-specific mediators whose gene expression in the colon is not inevitably sensitive to steroidal anti-inflammatory treatment. PMID

Surveillance of contrast-media-induced hypersensitivity reactions using signals from an electronic medical recording system.

PubMed

Kim, Min-Hye; Park, Chang-Han; Kim, Duk-In; Kim, Kyung-Mook; Kim, Hui-Kyu; Lim, Kyu-Hyoung; Song, Woo-Jung; Lee, Sang-Min; Kim, Sae-Hoon; Kwon, Hyouk-Soo; Park, Heung-Woo; Yoon, Chang-Jin; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Chang, Yoon-Seok

2012-03-01

Contrast-media (CM) hypersensitivity is a well-known adverse drug reaction. Surveillance of adverse drug reactions usually depends on spontaneous reports. However, the rate of spontaneous reports is low. Recent progress in information technology enables the electronic search on signals of adverse drug reactions from electronic medical recording (EMR) systems. To analyze the incidence and clinical characteristics of CM hypersensitivity using an EMR-based surveillance system. The surveillance system used signals from standardized terms within the international classification of nursing practice terms that can indicate symptoms of CM hypersensitivity and from the order codes for procedures that used contrast media, antihistamine, and epinephrine. The search strategy was validated by allergists comparing the electronic search strategy versus manually reviewing medical charts over one month. The main study covered for one year period. Detection rate of the electronic search method was 0.9% (7/759), while that of the manual search method was 0.8% (6/759). EMR-based electronic search method was highly efficient: reduced the charts that needed to be reviewed by 96% (28/759). The sensitivity of electronic screening was 66.7%, specificity was 99.6%, and the negative predictive value was 99.7%. CM hypersensitivity reactions were noted in 266 among 12,483 cases (2.1%). Urticaria was the most frequent symptom (74.4%). CT was the most frequent procedure (3.6%) that induced CM hypersensitivity. A surveillance system using EMR may be a useful tool in the study of drug hypersensitivity epidemiology and may be used in an adverse drug reaction alarm system and as a clinical, decision making support system. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Association of Human Leukocyte Antigen Alleles and Nevirapine Hypersensitivity in a Malawian HIV-Infected Population

PubMed Central

Carr, Daniel F.; Chaponda, Mas; Jorgensen, Andrea L.; Castro, Elena Cornejo; van Oosterhout, Joep J.; Khoo, Saye H.; Lalloo, David G.; Heyderman, Robert S.; Alfirevic, Ana; Pirmohamed, Munir

2013-01-01

Background. The nonnucleoside reverse transcriptase inhibitor nevirapine is the cornerstone of treatment for human immunodeficiency virus (HIV) in many sub-Saharan African countries. However, nevirapine is associated with a 6%–10% risk of developing a hypersensitivity reaction, with different phenotypes, including the blistering conditions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Our aim was to identify predictive human leukocyte antigen (HLA) markers that are associated with nevirapine hypersensitivity. Methods. We identified 117 HIV-infected Malawian adults with nevirapine hypersensitivity (15 drug-induced liver injury [DILI], 33 SJS/TEN, 20 hypersensitivity syndrome, and 46 nevirapine-induced rash plus 3 with both DILI and SJS phenotype) and 155 age-, sex- and ethnicity-matched nevirapine-exposed controls. HLA typing for 5 loci (A, B, C, DRB1, and DQB1) was undertaken using a sequence-based high-resolution protocol. Logistic regression analysis included CD4+ cell count as a covariate. Results. HLA-C*04:01 was found to markedly increase the risk for SJS (odds ratio [OR] = 17.52; 95% confidence interval, 3.31–92.80) and all hypersensitivity phenotypes (OR = 2.64; 95% CI, 1.13–6.18) when compared to the baseline rare allele group in a binary logistic regression model. The OR for absolute risk of SJS/TEN associated with carriage of HLA-C*04:01 was 5.17 (95% CI, 2.39–11.18). Positive predictive value was 2.6% and negative predictive value was 99.2%. In addition, a number of alleles within the HLA-DQB1 loci protected against nevirapine-induced hypersensitivity phenotypes. Conclusions. Our study has identified HLA-C*04:01 carriage as a risk factor for nevirapine-induced SJS/TEN in a Malawian HIV cohort. Validation of these findings in a larger cohort of patients and mechanistic investigation of the pathogenesis are required. PMID:23362284

Performance of genetic risk factors in prediction of trichloroethylene induced hypersensitivity syndrome.

PubMed

Dai, Yufei; Chen, Ying; Huang, Hanlin; Zhou, Wei; Niu, Yong; Zhang, Mingrong; Bin, Ping; Dong, Haiyan; Jia, Qiang; Huang, Jianxun; Yi, Juan; Liao, Qijun; Li, Haishan; Teng, Yanxia; Zang, Dan; Zhai, Qingfeng; Duan, Huawei; Shen, Juan; He, Jiaxi; Meng, Tao; Sha, Yan; Shen, Meili; Ye, Meng; Jia, Xiaowei; Xiang, Yingping; Huang, Huiping; Wu, Qifeng; Shi, Mingming; Huang, Xianqing; Yang, Huanming; Luo, Longhai; Li, Sai; Li, Lin; Zhao, Jinyang; Li, Laiyu; Wang, Jun; Zheng, Yuxin

2015-07-20

Trichloroethylene induced hypersensitivity syndrome is dose-independent and potentially life threatening disease, which has become one of the serious occupational health issues and requires intensive treatment. To discover the genetic risk factors and evaluate the performance of risk prediction model for the disease, we conducted genomewide association study and replication study with total of 174 cases and 1761 trichloroethylene-tolerant controls. Fifty seven SNPs that exceeded the threshold for genome-wide significance (P < 5 × 10(-8)) were screened to relate with the disease, among which two independent SNPs were identified, that is rs2857281 at MICA (odds ratio, 11.92; P meta = 1.33 × 10(-37)) and rs2523557 between HLA-B and MICA (odds ratio, 7.33; P meta = 8.79 × 10(-35)). The genetic risk score with these two SNPs explains at least 20.9% of the disease variance and up to 32.5-fold variation in inter-individual risk. Combining of two SNPs as predictors for the disease would have accuracy of 80.73%, the area under receiver operator characteristic curves (AUC) scores was 0.82 with sensitivity of 74% and specificity of 85%, which was considered to have excellent discrimination for the disease, and could be considered for translational application for screening employees before exposure.

Carboplatin hypersensitivity: evaluation and successful desensitization protocol.

PubMed

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

2014-01-01

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

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

PubMed

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

2010-09-01

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

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

PubMed

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

2016-01-01

The use of carboplatin for the treatment of pediatric low grade gliomas (PLGG) is often limited by the development of carboplatin hypersensitivity. Reported rates of carboplatin hypersensitivity reactions vary between 6% and 32% in these patients. Here we report the frequency of carboplatin hypersensitivity reactions depending on the treatment regimen used, and outcomes of carboplatin desensitization. The records of all patients in a single institution who were treated with carboplatin for PLGG were accessed and all patients receiving more than one dose of carboplatin are reported. Thirty four patients with PLGG were treated with carboplatin according to one of the two different regimens. Carboplatin hypersensitivity was documented in 47% of patients, but the frequency differed by treatment protocol. Those patients treated with 4-weekly single agent carboplatin had carboplatin allergy in 8% of cases whereas 68% of those treated with combined carboplatin and vincristine (every three weeks, according to the SIOP 2004 low grade glioma protocol) had carboplatin reactions (OR 23.6, P < 0.01). Desensitization was only successful in two out of 10 patients in whom it was attempted. Hypersensitivity reactions to carboplatin are more common in this cohort than previously reported and rates are protocol-dependent. Desensitization showed limited effectiveness in this cohort. © 2015 Wiley Periodicals, Inc.

[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.

Studies of the quenching phenomenon in delayed contact hypersensitivity reactions.

PubMed

Basketter, D A; Allenby, C F

1991-09-01

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

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

Testing for Drug Hypersensitivity Syndromes

PubMed Central

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

2013-01-01

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

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.

Dissociation between the relief of skeletal pain behaviors and skin hypersensitivity in a model of bone cancer pain

PubMed Central

Guedon, Jean-Marc G.; Longo, Geraldine; Majuta, Lisa A.; Thomspon, Michelle L.; Fealk, Michelle N.; Mantyh, Patrick W.

2016-01-01

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 was 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 hindpaw. 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 while 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 endpoints for clinical trials. PMID:27186713

The efficacy of prophylactic antibiotics in the management of children with kerosene-associated pneumonitis: a double-blind randomised controlled trial.

PubMed

Balme, Kate H; Zar, Heather; Swift, Donne K; Mann, Michael D

2015-01-01

Hydrocarbons, especially kerosene (paraffin), are the most common agents causing childhood poisoning in low and middle income countries (LMICs). Aspiration of kerosene causes an inflammatory sterile chemical pneumonitis, which may increase susceptibility to secondary lower respiratory tract bacterial infection. This study aimed to assess the efficacy of prophylactic antibiotics in the management of kerosene-associated pneumonitis in children and to identify risk factors associated with severity or outcome. A double-blind placebo-controlled trial of prophylactic antibiotics in the management of kerosene-associated pneumonitis of children presenting to a referral hospital was performed from July 2010 to September 2011. Sequential children with a history of kerosene ingestion and mild respiratory illness were randomised to receive placebo or amoxicillin. Each child was followed-up at Day 3 and Day 5 post-ingestion. The primary outcome measure was the number of treatment failures in each group, defined as any child who deteriorated within this time, necessitating a change in treatment regimen. Secondary outcome measures were length of hospital stay and symptoms and signs at follow-up. Seventy-four patients were enrolled. Thirty-five (47%) received placebo and 39 (53%) active treatment. There was no significant difference in treatment failures between placebo (3/35, 9%; 95% CI, 3-22) and active (2/39, 5%; 95% CI, 1-17) groups (relative risk, 0.60; 95% CI, 0.11-3.37). The median length of hospital stay was identical (placebo 0.5 days; IQR, 0-1.0 and active 0.5 days; IQR, 0.5-1.0). Symptoms and signs at Days 3 and 5 post-ingestion were similar. The only significant risk factor for treatment failure was residence in formal housing. Clinical severity at presentation was similar for treatment successes and failures. Prophylactic antibiotics do not improve the outcome in children with mild respiratory illness after kerosene ingestion.

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. © The Author(s) 2014.

HLA-A*31:01 and HLA-B*15:02 as genetic markers for carbamazepine hypersensitivity in children

PubMed Central

Amstutz, Ursula; Ross, Colin J.D.; Castro-Pastrana, Lucila I.; Rieder, Michael J.; Shear, Neil H.; Hayden, Michael R.; Carleton, Bruce C.

2013-01-01

The occurrence of hypersensitivity reactions including rare but life-threatening Stevens-Johnson syndrome (SJS) and drug-induced hypersensitivity syndrome (HSS) limits the use of the anticonvulsant carbamazepine (CBZ). HLA-B*15:02 and HLA-A*31:01 have been identified as predictive genetic markers for CBZ hypersensitivity in Asian and European patients. To replicate these genetic associations in pediatric patients from North America with a diverse ethnic background, we investigated HLA-A*31:01 and HLA-B*15:02 in 42 children with CBZ hypersensitivity, and 91 CBZ-tolerant children from across Canada. HLA-A*31:01 was significantly associated with CBZ-HSS (odds ratio (OR): 26.4, p=0.0025) and maculopapular exanthems (OR: 8.6, p=0.0037), but not with CBZ-SJS. Conversely, HLA-B*15:02 was associated with CBZ-SJS (OR: 38.6, p=0.002), but not HSS and maculopapular exanthems. This study is the first to demonstrate the association of HLA-A*31:01 with CBZ hypersensitivity in children, providing important replication of this association and highlighting the importance of HLA-A*31:01 as a predictive biomarker across various ancestries. PMID:23588310

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

PubMed Central

Kutszegi, Nóra; Semsei, Ágnes F.; Gézsi, András; Sági, Judit C.; Nagy, Viktória; Csordás, Katalin; Jakab, Zsuzsanna; Lautner-Csorba, Orsolya; Gábor, Krisztina Míta; Kovács, Gábor T.; Erdélyi, Dániel J.; Szalai, Csaba

2015-01-01

L-asparaginase (ASP) is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL). However, hypersensitivity reactions (HSRs) to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin—Frankfurt—Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs) in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01–0.26); p = 4.70E-04), while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176) were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09–0.53); p = 8.48E-04 and OR = 3.02 (1.36–6.73); p = 6.76E-03, respectively). Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect. PMID:26457809

The Effectiveness of Automatic Recommending System for Premedication in Reducing Recurrent Radiocontrast Media Hypersensitivity Reactions

PubMed Central

Bae, Yun-Jeong; Hwang, Ye Won; Yoon, Sun-young; Kim, Sujeong; Lee, Taehoon; Lee, Yoon Su; Kwon, Hyouk-Soo; Cho, You Sook; Shin, Myung Jin; Moon, Hee-Bom; Kim, Tae-Bum

2013-01-01

Background Non-ionic radiocontrast media (RCM) is rarely associated with hypersensitivity reactions. Premedication of patients who reacted previously to RCM with systemic corticosteroids and/or antihistamines can help reduce recurrent hypersensitivity reactions. However, premedication is still not prescribed in many cases for various reasons. This study aimed to determine the effectiveness of our novel RCM hypersensitivity surveillance and automatic recommending system for premedication. Methods and Results Hospitalized patients with a history of RCM hypersensitivity were identified in an electronic medical record system that included a mandatory reporting system for past adverse drug reactions. In 2009, a novel automatic prescription system was added that classified index RCM reactions by severity and dispensed appropriate corticosteroid and/or antihistamine pretreatment prior to new RCM exposures. The data from 12 months under the previous system and 12 months under the current system were compared. The two systems had similar overall premedication rates (91% and 95%) but the current system was associated with a significantly higher corticosteroid premedication rate (65% vs. 14%), which significantly reduced the breakthrough reaction rate (6.7% vs. 15.2%). The current system was also associated with increased corticosteroid and antihistamine premedication of patients with a mild index reaction (61% vs. 7%) and a reduction in their breakthrough reaction rate (6% vs. 15%). Conclusions Premedication with corticosteroid and/or antihistamine, which was increased by our novel automatic prescription system, significantly reduced breakthrough reactions in patients with a history of RCM hypersensitivity. PMID:23840391

Linezolid desensitization for a patient with multiple medication hypersensitivity reactions.

PubMed

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

2013-01-01

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

Antibiotic Therapy in Comatose Mechanically Ventilated Patients Following Aspiration: Differentiating Pneumonia From Pneumonitis.

PubMed

Lascarrou, Jean Baptiste; Lissonde, Floriane; Le Thuaut, Aurélie; Bachoumas, Konstantinos; Colin, Gwenhael; Henry Lagarrigue, Matthieu; Vinatier, Isabelle; Fiancette, Maud; Lacherade, Jean Claude; Yehia, Aihem; Joret, Aurélie; Lebert, Christine; Bourdon, Sandra; Martin Lefèvre, Laurent; Reignier, Jean

2017-08-01

To determine the proportion of patients with documented bacterial aspiration pneumonia among comatose ICU patients with symptoms suggesting either bacterial aspiration pneumonia or non-bacterial aspiration pneumonitis. Prospective observational study. University-affiliated 30-bed ICU. Prospective cohort of 250 patients admitted to the ICU with coma (Glasgow Coma Scale score ≤ 8) and treated with invasive mechanical ventilation. None. The primary outcome was the proportion of patients with microbiologically documented bacterial aspiration pneumonia. Patients meeting predefined criteria for aspiration syndrome routinely underwent telescopic plugged catheter sampling during bronchoscopy before starting probabilistic antibiotic treatment. When cultures were negative, the antibiotic treatment was stopped. Of 250 included patients, 98 (39.2%) had aspiration syndrome, including 92 before mechanical ventilation discontinuation. Telescopic plugged catheter in these 92 patients showed bacterial aspiration pneumonia in 43 patients (46.7%). Among the remaining 49 patients, 16 continued to receive antibiotics, usually for infections other than pneumonia; of the 33 patients whose antibiotics were discontinued, only two subsequently showed signs of lung infection. In the six patients with aspiration syndrome after mechanical ventilation, and therefore without telescopic plugged catheter, antibiotic treatment was continued for 7 days. Mechanical ventilation duration, ICU length of stay, and mortality did not differ between the 43 patients with bacterial aspiration pneumonia and the 49 patients with non-bacterial aspiration pneumonitis. The 152 patients without aspiration syndrome did not receive antibiotics. Among comatose patients receiving mechanical ventilation, those without clinical, laboratory, or radiologic evidence of bacterial aspiration pneumonia did not require antibiotics. In those with suspected bacterial aspiration pneumonia, stopping empirical antibiotic therapy

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.

[Low salicylate diet in hypersensitivity to nonsteroidal anti-inflammatory drugs].

PubMed

Ignacak, Maria; Mastalerz, Lucyna

2015-01-01

The article below shows different forms, patomechanisms and diagnostics criteria of hypersensitivity to NSAIDs based on available literature as well as up to date outlook on implementing low salicylate diet as a treatment.

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

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

PubMed

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

2016-06-14

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

A rapid, efficient, and facile solution for dental hypersensitivity: The tannin–iron complex

PubMed Central

Oh, Dongyeop X.; Prajatelistia, Ekavianty; Ju, Sung-Won; Jeong Kim, Hyo; Baek, Soo-Jin; Joon Cha, Hyung; Ho Jun, Sang; Ahn, Jin-Soo; Soo Hwang, Dong

2015-01-01

Dental hypersensitivity due to exposure of dentinal tubules under the enamel layer to saliva is a very popular and highly elusive technology priority in dentistry. Blocking water flow within exposed dentinal tubules is a key principle for curing dental hypersensitivity. Some salts used in “at home” solutions remineralize the tubules inside by concentrating saliva ingredients. An “in-office” option of applying dense resin sealants on the tubule entrance has only localized effects on well-defined sore spots. We report a self-assembled film that was formed by facile, rapid (4 min), and efficient (approximately 0.5 g/L concentration) dip-coating of teeth in an aqueous solution containing a tannic acid–iron(III) complex. It quickly and effectively occluded the dentinal tubules of human teeth. It withstood intense tooth brushing and induced hydroxyapatite remineralisation within the dentinal tubules. This strategy holds great promise for future applications as an effective and user-friendly desensitizer for managing dental hypersensitivity. PMID:26039461

A rapid, efficient, and facile solution for dental hypersensitivity: The tannin-iron complex.

PubMed

Oh, Dongyeop X; Prajatelistia, Ekavianty; Ju, Sung-Won; Jeong Kim, Hyo; Baek, Soo-Jin; Joon Cha, Hyung; Ho Jun, Sang; Ahn, Jin-Soo; Soo Hwang, Dong

2015-06-03

Dental hypersensitivity due to exposure of dentinal tubules under the enamel layer to saliva is a very popular and highly elusive technology priority in dentistry. Blocking water flow within exposed dentinal tubules is a key principle for curing dental hypersensitivity. Some salts used in "at home" solutions remineralize the tubules inside by concentrating saliva ingredients. An "in-office" option of applying dense resin sealants on the tubule entrance has only localized effects on well-defined sore spots. We report a self-assembled film that was formed by facile, rapid (4 min), and efficient (approximately 0.5 g/L concentration) dip-coating of teeth in an aqueous solution containing a tannic acid-iron(III) complex. It quickly and effectively occluded the dentinal tubules of human teeth. It withstood intense tooth brushing and induced hydroxyapatite remineralisation within the dentinal tubules. This strategy holds great promise for future applications as an effective and user-friendly desensitizer for managing dental hypersensitivity.

A systematic review of validated methods for identifying hypersensitivity reactions other than anaphylaxis (fever, rash, and lymphadenopathy), using administrative and claims data.

PubMed

Schneider, Gary; Kachroo, Sumesh; Jones, Natalie; Crean, Sheila; Rotella, Philip; Avetisyan, Ruzan; Reynolds, Matthew W

2012-01-01

The Food and Drug Administration's Mini-Sentinel pilot program aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest from administrative and claims data. This article summarizes the process and findings of the algorithm review of hypersensitivity reactions. PubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the hypersensitivity reactions of health outcomes of interest. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify hypersensitivity reactions and including validation estimates of the coding algorithms. We identified five studies that provided validated hypersensitivity-reaction algorithms. Algorithm positive predictive values (PPVs) for various definitions of hypersensitivity reactions ranged from 3% to 95%. PPVs were high (i.e. 90%-95%) when both exposures and diagnoses were very specific. PPV generally decreased when the definition of hypersensitivity was expanded, except in one study that used data mining methodology for algorithm development. The ability of coding algorithms to identify hypersensitivity reactions varied, with decreasing performance occurring with expanded outcome definitions. This examination of hypersensitivity-reaction coding algorithms provides an example of surveillance bias resulting from outcome definitions that include mild cases. Data mining may provide tools for algorithm development for hypersensitivity and other health outcomes. Research needs to be conducted on designing validation studies to test hypersensitivity-reaction algorithms and estimating their predictive power, sensitivity, and specificity. Copyright © 2012 John Wiley & Sons, Ltd.

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

PubMed

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

2013-07-01

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. 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. 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 inhibition of photosynthesis, elevated levels of

In vitro analysis of metabolic predisposition to drug hypersensitivity reactions.

PubMed Central

Riley, R J; Leeder, J S

1995-01-01

Idiosyncratic hypersensitivity reactions may account for up to 25% of all adverse reactions, and pose a constant problem to physicians because of their unpredictable nature, potentially fatal outcome and resemblance to other disease processes. Current understanding of how drug allergy arises is based largely on the hapten hypothesis: since most drugs are not chemically reactive per se, they must be activated metabolically to reactive species which may become immunogenic through interactions with cellular macromolecules. The role of drug metabolism is thus pivotal to the hapten hypothesis both in activation of the parent compound and detoxification of the reactive species. Although conjugation reactions may occasionally produce potential immunogens (for example, the generation of acylglucuronides from non-steroidal anti-inflammatory drugs such as diclofenac), bioactivation is catalysed most frequently by cytochrome P450 (P450) enzymes. The multifactorial nature of hypersensitivity reactions, particularly the role of often unidentified, reactive drug metabolites in antigen generation, has hampered the routine diagnosis of these disorders by classical immunological methods designed to detect circulating antibodies or sensitized T cells. Similarly, species differences in drug metabolism and immune system regulation have largely precluded the establishment of appropriate animal models with which to examine the immunopathological mechanisms of these toxicities. However, the combined use of in vitro toxicity assays incorporating human tissues and in vivo phenotyping (or, ultimately, in vitro genotyping) methods for drug detoxification pathways may provide the metabolic basis for hypersensitivity reactions to several drugs. This brief review highlights recent efforts to unravel the bases for hypersensitivity reactions to these therapeutic agents (which include anticonvulsants and sulphonamides) using drug metabolism and immunochemical approaches. In particular, examples

Common allergies do not influence the prevalence of cutaneous hypersensitivity reactions to antiepileptic drugs.

PubMed

Bosak, Magdalena; Porębski, Grzegorz; Słowik, Agnieszka; Turaj, Wojciech

2017-09-01

The aim of the study was to establish whether the presence of common allergies increases the risk of drug-related hypersensitivity reactions among patients with epilepsy treated with antiepileptic drugs (AEDs). We studied 753 patients with epilepsy seen in tertiary outpatient epilepsy clinic. We obtained data related to epilepsy type, past and ongoing treatment with AEDs, occurrence of maculopapular exanthema or more serious cutaneous adverse reactions (Stevens-Johnson syndrome - SJS) and their characteristics. We noted an occurrence of allergic reactions unrelated to treatment with AED, including rash unrelated to AED, bronchial asthma, persistent or seasonal allergic rhinitis, atopic dermatitis, rash after specific food and other allergic reactions. There were 61 cases of AED-related cutaneous hypersensitivity reaction (including 3 cases of SJS) noted in association with 2319 exposures to AEDs (2.63%) among 55 out of 753 patients (7.3%). Cutaneous hypersensitivity reaction to AED was most commonly noted after lamotrigine (12.1%), carbamazepine (5.4%) and oxcarbazepine (4.1%). Prevalence of allergic reactions unrelated to AED was similar between patients with and without AED-related cutaneous hypersensitivity reaction (rash unrelated to AED: 16.4% vs. 10.2%; bronchial asthma: 1.8% vs. 0.1%; persistent allergic rhinitis: 7.3% vs. 10.2%; seasonal allergic rhinitis: 7.3% vs. 11.7%; atopic dermatitis: 0 vs. 0.7%; rash after specific food: 5.4% vs. 6.4%; other allergic reactions: 5.4% vs. 5.2%, respectively; P>0.1 for each difference). Presence of common allergies is not a significant risk factor for AED-related cutaneous hypersensitivity reaction among patients with epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

Opioid Hypersensitivity: Predictors of Allergy and Role of Drug Provocation Testing.

PubMed

Li, Philip H; Ue, Kok Loong; Wagner, Annette; Rutkowski, Ryszard; Rutkowski, Krzysztof

True IgE-mediated hypersensitivity to opioids is rare and many reactions are due to direct mast cell degranulation. Opioid drug provocation testing (DPT) is the gold standard for diagnosis but is underutilized. The objective of this study was to evaluate the clinical characteristics and predictors of opioid hypersensitivity, as well as outcomes of opioid DPT. Patients referred for opioid DPT over the past 9 years were studied. Patient characteristics, indications for opioid use, symptoms of index reaction, and outcomes of DPT were analyzed. Association analysis was performed to study variables associated with a diagnosis of opioid hypersensitivity. Of the total of 98 patients referred with suspected opioid hypersensitivity, 15 (15%) were diagnosed with opioid allergy. Angioedema (odds ratio [OR]: 5.66; 95% confidence interval [CI]: 1.49-21.47; P = .011) and hypotension (OR: 5.00; 95% CI: 1.15-21.70; P = .032) were significantly more frequent in opioid allergic patients than those with a negative DPT. Patients who received opioids during anesthesia were significantly more likely to be opioid allergic (OR: 6.74; 95% CI: 2.05-22.13; P = .001). In contrast, a negative association was identified with patients who received opioids for analgesia (OR: 0.27; 95% CI: 0.08-0.86; P = .008). Only 15% of our cohort were diagnosed with opioid allergy, emphasizing the importance of DPT in preventing erroneous overdiagnosis. Patients with a history of angioedema or hypotension as their index reaction were significantly more likely to be opioid allergic. DPT are safe when performed by experienced clinicians after risk stratification and using individualized protocols. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Parathyroid Hormone-Related Peptide Elicits Peripheral TRPV1-dependent Mechanical Hypersensitivity

PubMed Central

Shepherd, Andrew J.; Mickle, Aaron D.; Kadunganattil, Suraj; Hu, Hongzhen; Mohapatra, Durga P.

2018-01-01

Bone metastasis in breast, prostate and lung cancers often leads to chronic pain, which is poorly managed by existing analgesics. The neurobiological mechanisms that underlie chronic pain associated with bone-metastasized cancers are not well understood, but sensitization of peripheral nociceptors by tumor microenvironment factors has been demonstrated to be important. Parathyroid hormone-related peptide (PTHrP) is highly expressed in bone-metastasized breast and prostate cancers, and is critical to growth and proliferation of these tumors in the bone tumor microenvironment. Previous studies have suggested that PTHrP could sensitize nociceptive sensory neurons, resulting in peripheral pain hypersensitivity. In this study, we found that PTHrP induces both heat and mechanical hypersensitivity, that are dependent on the pain-transducing transient receptor potential channel family vanilloid, member-1 (TRPV1), but not the mechano-transducing TRPV4 and TRPA1 ion channels. Functional ratiometric Ca2+ imaging and voltage-clamp electrophysiological analysis of cultured mouse DRG neurons show significant potentiation of TRPV1, but not TRPA1 or TRPV4 channel activation by PTHrP. Interestingly, PTHrP exposure led to the slow and sustained activation of TRPV1, in the absence of any exogenous channel agonist, and is dependent on the expression of the type-1 parathyroid hormone receptor (PTH1), as well as on downstream phosphorylation of the channel by protein kinase C (PKC). Accordingly, local administration of specific small-molecule antagonists of TRPV1 to mouse hindpaws after the development of PTHrP-induced mechanical hypersensitivity led to its significant attenuation. Collectively, our findings suggest that PTHrP/PTH1-mediated flow activation of TRPV1 channel contributes at least in part to the development and maintenance of peripheral mechanical pain hypersensitivity, and could therefore constitute a mechanism for nociceptor sensitization in the context of metastatic bone

Risk Factors for Oxaliplatin-Induced Hypersensitivity Reactions in Japanese Patients with Advanced Colorectal Cancer

PubMed Central

Seki, Kyoko; Senzaki, Kenzou; Tsuduki, Yasuo; Ioroi, Takeshi; Fujii, Michiko; Yamauchi, Hiroko; Shiraishi, Yukinari; Nakata, Izumi; Nishiguchi, Kohshi; Matsubayashi, Teruhisa; Takakubo, Yoshihide; Okamura, Noboru; Yamamori, Motohiro; Tamura, Takao; Sakaeda, Toshiyuki

2011-01-01

Objective: Previously, we suggested that oxaliplatin (L-OHP)-related grade 3/4 hypersensitivity reactions occurred immediately after the initiation, but grade 1/2 reactions did not. This study was conducted to clarify the risk factors for L-OHP-related hypersensitivity reactions. Methods: Clinical data from 108 Japanese patients with colorectal cancer were analyzed, who were treated with L-OHP-containing regimens, FOLFOX4 and/or mFOLFOX6. The risk factors examined included demographic data, preexisting allergies, laboratory test data, treatment regimen, treatment line of therapy, pretreatment with steroids, total number of cycles and cumulative amount of L-OHP. Results: The incidence of grade 1/2 and grade 3/4 hypersensitivity reactions were found at 13.0% (14/108) and 9.3% (10/108), respectively. Female (P=0.037), preexisting allergies (P=0.004) and lower level of lactate dehydrogenase (P=0.003) were risk factors for grade 1/2 hypersensitivity reactions, and higher neutrophil count (P=0.043) and lower monocyte count (P=0.007) were for grade 3/4 reactions. Total number of cycles were larger in the patients with grade 3/4 reactions than those without reactions (P=0.049). Conclusions: Further extensive examination with a large number of patients is needed to establish a patient management strategy. PMID:21448307

The Role of Esophageal Hypersensitivity in Functional Heartburn.

PubMed

Kondo, Takashi; Miwa, Hiroto

2017-08-01

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

Hypersensitivity to sub-Tenon's topotecan in fibrin adhesive in patients with retinoblastoma.

PubMed

Astudillo, Paulita Pamela P; Durairaj, Priya; Chan, Helen S L; Héon, Elise; Gallie, Brenda L

2015-02-01

Sub-Tenon's space delivery of topotecan in a fibrin sealant was used as an adjunct to laser therapy for small retinoblastoma tumors in 25 children (77 injections). We report serious hypersensitivity reactions in 2 children on their third sub-Tenon's injection of topotecan in fibrin sealant. One child subsequently had topotecan in an autologous blood clot with no allergic reaction. Although allergic reaction to topotecan has been reported in the literature, fibrin glue reactions are more common and are likely due to aprotinin hypersensitivity. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Glycerol Hypersensitivity in a Drosophila Model for Glycerol Kinase Deficiency Is Affected by Mutations in Eye Pigmentation Genes

PubMed Central

Wightman, Patrick J.; Jackson, George R.; Dipple, Katrina M.

2012-01-01

Glycerol kinase plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP dependent reaction. In humans, glycerol kinase deficiency results in a wide range of phenotypic variability; patients can have severe metabolic and CNS abnormalities, while others possess hyperglycerolemia and glyceroluria with no other apparent phenotype. In an effort to help understand the pathogenic mechanisms underlying the phenotypic variation, we have created a Drosophila model for glycerol kinase deficiency by RNAi targeting of dGyk (CG18374) and dGK (CG7995). As expected, RNAi flies have reduced glycerol kinase RNA expression, reduced phosphorylation activity and elevated glycerol levels. Further investigation revealed these flies to be hypersensitive to fly food supplemented with glycerol. Due to the hygroscopic nature of glycerol, we predict glycerol hypersensitivity is a result of greater susceptibility to desiccation, suggesting glycerol kinase to play an important role in desiccation resistance in insects. To evaluate a role for genetic modifier loci in determining severity of the glycerol hypersensitivity observed in knockdown flies, we performed a preliminary screen of lethal transposon insertion mutant flies using a glycerol hypersensitive survivorship assay. We demonstrate that this type of screen can identify both enhancer and suppressor genetic loci of glycerol hypersensitivity. Furthermore, we found that the glycerol hypersensitivity phenotype can be enhanced or suppressed by null mutations in eye pigmentation genes. Taken together, our data suggest proteins encoded by eye pigmentation genes play an important role in desiccation resistance and that eye pigmentation genes are strong modifiers of the glycerol hypersensitive phenotype identified in our Drosophila model for glycerol kinase deficiency. PMID:22427807

Polymorphism in glutamate cysteine ligase catalytic subunit (GCLC) is associated with sulfamethoxazole-induced hypersensitivity in HIV/AIDS patients

PubMed Central

2012-01-01

Background Sulfamethoxazole (SMX) is a commonly used antibiotic for prevention of infectious diseases associated with HIV/AIDS and immune-compromised states. SMX-induced hypersensitivity is an idiosyncratic cutaneous drug reaction with genetic components. Here, we tested association of candidate genes involved in SMX bioactivation and antioxidant defense with SMX-induced hypersensitivity. Results Seventy seven single nucleotide polymorphisms (SNPs) from 14 candidate genes were genotyped and assessed for association with SMX-induced hypersensitivity, in a cohort of 171 HIV/AIDS patients. SNP rs761142 T > G, in glutamate cysteine ligase catalytic subunit (GCLC), was significantly associated with SMX-induced hypersensitivity, with an adjusted p value of 0.045. This result was replicated in a second cohort of 249 patients (p = 0.025). In the combined cohort, heterozygous and homozygous carriers of the minor G allele were at increased risk of developing hypersensitivity (GT vs TT, odds ratio = 2.2, 95% CL 1.4-3.7, p = 0.0014; GG vs TT, odds ratio = 3.3, 95% CL 1.6 – 6.8, p = 0.0010). Each minor allele copy increased risk of developing hypersensitivity 1.9 fold (95% CL 1.4 – 2.6, p = 0.00012). Moreover, in 91 human livers and 84 B-lymphocytes samples, SNP rs761142 homozygous G allele carriers expressed significantly less GCLC mRNA than homozygous TT carriers (p < 0.05). Conclusions rs761142 in GCLC was found to be associated with reduced GCLC mRNA expression and with SMX-induced hypersensitivity in HIV/AIDS patients. Catalyzing a critical step in glutathione biosynthesis, GCLC may play a broad role in idiosyncratic drug reactions. PMID:22824134

[Questionnaire about the intake of and hypersensitivity to fruits, vegetables and nuts including birch pollen related foods].

PubMed

Yamamoto, Tetsuo; Asakura, Kohji; Shirasaki, Hideaki; Himi, Tetsuo

2013-07-01

In Hokkaido and Scandinavia, birch pollen allergic persons are common and they often report oral and pharyngeal hypersensitivity to fruits and vegetables (oral allergy syndrome, OAS), because of immunological cross-reactivity. In Scandinavia, nuts as well as Rosaceae fruits such as apples were the foods most often reported to elicit symptoms. On the other hand, nuts are minor foods causing hypersensitivity in Japan. Even in Japan, regional differences of foods causing hypersensitivity have been reported, which may be related to the regional differences of elementary habit and pollen dispersion. In the present study, we evaluated the intake history of the foods and the frequency of food hypersensitivity in adults from the general population. Three hundreds and thirty nine subjects (20-67 years old) took part in the study. With a questionnaire survey, we asked them about their intake history and hypersensitive symptoms for 33 kinds of fruit, vegetables, and nuts. 30% of subjects had eaten Brazil nuts, 80% had eaten pomegranates, and 81% had eaten hazelnuts. And over 95% of subjects had eaten the other 30 foods. Those who had lived in Hokkaido for more than 20 years had a higher frequency of plum consumption than the others. Those who had lived in Hokkaido for more than 20 years had a lower frequency of loquat, fig and pomegranate consumption than the others. Food hypersensitivity was found in 52 subjects (15.3%). The most common symptom was OAS (46 subjects, 13.6%), and foods most frequently causing OAS were peach (21 subjects, 6.2%), cherry (19 subjects, 5.6%) and apple (17 subjects, 5.0%). 26 subjects (7.7%) reported OAS to Rosaceae fruits. The ratio of having OAS to consuming Rosaceae fruits was 11.0% in the group who had lived in Hokkaido for more than 20 years, which was higher than the group who has lived in Hokkaido for less than 20 years. The intake history of hazelnuts and Brazil nuts was very low, with a correspondingly low frequency of food

Cyproterone acetate in the treatment of oestrogen hypersensitivity vulvovaginitis.

PubMed

Nguyen, Yvonne; Bradford, Jennifer; Fischer, Gayle

2018-02-01

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

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. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

Is Tadpole Pupil in an Adolescent Girl Caused by Denervation Hypersensitivity?

PubMed

Hansen, Jonas Kjeldbjerg; Møller, Hans Ulrik

2017-06-01

Tadpole pupil is a rarely encountered phenomenon caused by episodic, segmental iris dilator muscle spasm of short duration (2-15 minutes), occurring in clusters without a known precipitating factor. It has most commonly been described in women aged 28 to 48 years. A few hypotheses on pathogenesis have been discussed but none has been proved. Here, we present an adolescent girl with bilateral tadpole pupil that appeared during physical exercise. This is the first pediatric case of tadpole pupil, not caused by preceding surgery, to be published. Based on (1) this case in which tadpole pupil developed when the norepinephrine level rose during exercise, (2) the high ratio of patients with tadpole pupil who concurrently have or later develop Horner syndrome, in which denervation hypersensitivity is well described, (3) a previous report of a patient with both tadpole pupil and Horner syndrome who had denervation hypersensitivity on pharmacological testing, (4) a 29-year-old man with unilateral tadpole pupil induced by exercise, and (5) a 19-year-old man with bilateral tadpole pupil and possible autonomic neuropathy, we suggest denervation hypersensitivity as a probable pathogenic mechanism causing tadpole pupil. In addition, a suggestion for investigations to be performed in future pediatric cases is provided. Georg Thieme Verlag KG Stuttgart · New York.

Making Sense of Metal Allergy and Hypersensitivity to Metallic Implants in Relation to Hand Surgery.

PubMed

Christensen, Thomas J; Samant, Shefali A; Shin, Alexander Y

2017-09-01

All metals implanted into a biological system undergo some degree of corrosion depending upon its composition. The electrochemical process of corrosion produces free metal ions, which may activate the host's immune system through a variety of mechanisms. Whereas dermal metal hypersensitivity is common, affecting 10% to 15% of the population, the immune reaction from implanted metals is much less common (< 0.1%), but has been associated with metal allergy and hypersensitivity producing a multitude of patient symptoms. Superficial symptoms may be mild to severe forms of dermatitis, urticaria, pruritus, and vasculitis, whereas deep sequelae include metallosis-related pseudotumor, implant loosening, and joint stiffness. Currently, there are clinical tests to evaluate patients for metal hypersensitivity, but there is little agreement regarding the ideal timing and clinical situation prompting the work-up of a patient for a metal allergy or hypersensitivity. An understanding of the epidemiology, etiology, basic science, diagnostic testing, and treatment of patients with suspected metal allergy, as it pertains to the current literature, will aid orthopedic and plastic surgeons of all subspecialties in the management of patients requiring metallic implants. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru

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 ofmore » 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

LETTER TO THE EDITOR: Clinical validation of the LKB model and parameter sets for predicting radiation-induced pneumonitis from breast cancer radiotherapy

NASA Astrophysics Data System (ADS)

Tsougos, Ioannis; Mavroidis, Panayiotis; Theodorou, Kyriaki; Rajala, J.; Pitkänen, M. A.; Holli, K.; Ojala, A. T.; Hyödynmaa, S.; Järvenpää, Ritva; Lind, Bengt K.; Kappas, Constantin

2006-02-01

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

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

PubMed

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

2016-06-01

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

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.

Cough reflex hypersensitivity: A role for neurotrophins.

PubMed

El-Hashim, Ahmed Z; Jaffal, Sahar M

2017-03-01

Cough is one of the most common complaints for which sufferers seek medical assistance. However, currently available drugs are not very effective in treating cough, particularly that which follows an upper respiratory tract infection. Nonetheless, there has been a significant increase in our understanding of the mechanisms and pathways of the defensive cough as well as the hypersensitive/pathophysiological cough, both at airway and central nervous system (CNS) levels. Numerous molecules and signaling pathways have been identified as potential targets for antitussive drugs, including neurotrophins (NTs). NTs belong to a family of trophic factors and are critical for the development and maintenance of neurons in the central and peripheral nervous system including sympathetic efferents, sensory neuron afferents, and immune cells. Nerve growth factor (NGF) was the first member of the NT family to be discovered, with wide ranging actions associated with synapse formation, survival, proliferation, apoptosis, axonal and dendritic outgrowth, expression and activity of functionally important proteins such as ion channels, receptors, and neurotransmitters. In addition, NGF has been implicated in several disease states particularly neuropathic pain and most recently in the sensitization of the cough reflex. This review will briefly address the peripheral and central sensitization mechanisms of airway neurons and will then focus on NGF signaling and its role in cough hypersensitivity.

Imipramine for Treatment of Esophageal Hypersensitivity and Functional Heartburn: A Randomized Placebo-Controlled Trial.

PubMed

Limsrivilai, Julajak; Charatcharoenwitthaya, Phunchai; Pausawasdi, Nonthalee; Leelakusolvong, Somchai

2016-02-01

Tricyclic antidepressants could be effective in the treatment of symptoms related to hypersensitive esophagus through their pain-modulating effect. We therefore assessed the benefit of imipramine in patients with esophageal hypersensitivity and functional heartburn. Patients with normal endoscopy findings and typical reflux symptoms despite standard-dose proton-pump inhibitor therapy underwent 24-h pH-impedance monitoring. Patients with established esophageal hypersensitivity or functional heartburn were randomly assigned to receive 8 weeks of either once-daily imipramine 25 mg (n=43) or placebo (n=40). The primary end point was satisfactory relief of reflux symptoms, defined as a >50% reduction in the gastroesophageal reflux disease score. The secondary end point was improvement in quality-of-life (QoL) as assessed by the 36-Item Short Form Health Survey score. Patients receiving imipramine did not achieve a higher rate of satisfactory relief of reflux symptoms than did patients receiving placebo (intention-to-treat (ITT) analysis: 37.2 vs. 37.5%, respectively; odds ratio (OR), 0.99; 95% confidence interval (CI), 0.41-2.41; per-protocol (PP) analysis: 45.5 vs. 41.2%, respectively; OR, 1.19; 95% CI, 0.45-3.13). Subgroup analysis to assess the efficacy of imipramine for either esophageal hypersensitivity or functional heartburn yielded similar results. Treatment with imipramine provided significant improvement of QoL by PP analysis (72±17 and 61±19, respectively; P=0.048), but ITT analysis did not reveal any differences between imipramine and placebo (68±19 and 61±19, respectively; P=0.26). Adverse events were similar in both groups; however, constipation was more common with imipramine than placebo (51.2 vs. 22.5%, respectively; P=0.01). Although low-dose imipramine shows potential QoL benefits, it does not relieve symptoms more effectively than does placebo in patients with either esophageal hypersensitivity or functional heartburn.

Cross-protection against Salmonella enteritidis infection in mice. III. Delayed hypersensitivity reaction and clearance of the challenge organism.

PubMed

Padmanaban, V D; Mittal, K R

1979-01-01

Mice were immunized with live vaccines and with live vaccines with complete adjuvant incorporating Salmonella enteritidis, Salmonella typhi-murium, Salmonella gallinarum or Salmonella pullorum. On the 21st day after vacination, the hypersensitivity reactions elicited by the mice to extracts of the challenge organism (S. enteritidis 5694 SMR) were assessed. The degree of delayed hypersensitivity reaction was compared with the level of protection induced by the vaccine. The role in protection of delayed hypersensitivity is discussed. Clearance of the challenge organism from the liver of previously vaccinated and unvaccinated mice was assessed quantitatively.

Incidence and risk factors for food hypersensitivity in UK infants: results from a birth cohort study.

PubMed

Grimshaw, Kate E C; Bryant, Trevor; Oliver, Erin M; Martin, Jane; Maskell, Joe; Kemp, Terri; Clare Mills, E N; Foote, Keith D; Margetts, Barrie M; Beyer, Kirsten; Roberts, Graham

2015-01-01

The prevalence of food hypersensitivity in the UK is still largely open to debate. Additionally its pathogenesis is also unclear although it is known that there are differing phenotypes. Determining its prevalence, along with identifying those factors associated with its development will help to assess its clinical importance within the national setting and also add to the debate on appropriate prevention strategies. A population based birth cohort study conducted in Hampshire, UK as part of the EuroPrevall birth cohort study. 1140 infants were recruited with 823 being followed up until 2 years of age. Infants with suspected food reactions were assessed including specific IgE measurement and skin prick testing. Diagnosis of food hypersensitivity was by positive double-blind, placebo-controlled food challenge (DBPCFC) where symptoms up to 48 h after the end of the food challenge were considered indicative of a food hypersensitivity. Factors associated with food hypersensitivity and its two phenotypes of IgE-mediated and non-IgE-mediated disease were modelled in a multivariable logistic regression analysis. Cumulative incidence of food hypersensitivity by 2 years of age was 5.0 %. The cumulative incidence for individual food allergens were hens' egg 2.7 % (1.6-3.8); cows' milk 2.4 % (1.4-3.5); peanut 0.7 % (0.1-1.3); soy 0.4 % (0.0-0.8); wheat 0.2 % (0.0-0.5) and 0.1 % (0.0-0.32) for fish. The cumulative incidence of IgE-mediated food allergy was 2.6 % with 2.1 % reacting to hens' egg. For non-IgE-mediated food allergy the cumulative incidence was 2.4 % (cows' milk 1.7 %). Predictors for any food hypersensitivity were wheeze, maternal atopy, increasing gestational age, age at first solid food introduction and mean healthy dietary pattern score. Predictors for IgE mediated allergy were eczema, rhinitis and healthy dietary pattern score whereas for non-IgE-mediated food allergy the predictors were dog in the home, healthy dietary pattern score, maternal

Peripheral and central P2X3 receptor contributions to colon mechanosensitivity and hypersensitivity in the mouse

PubMed Central

Shinoda, Masamichi; Feng, Bin; Gebhart, G. F.

2009-01-01

Background & Aims Irritable bowel syndrome is characterized by altered sensory qualities, namely discomfort/pain and colorectal hypersensitivity. In mice, we examined the role of P2X3 receptors in colon mechanosensitivity and intracolonic zymosan-produced hypersensitivity, a model of persistent colon hypersensitivity without colon inflammation. Methods The visceromotor response (VMR) to colon distension (15 – 60 mmHg) was determined before and after intracolonic saline or zymosan (30 mg/mL, 0.1 mL, daily for 3 days) treatment. Colon pathology and intracolonic ATP release was assessed in parallel experiments. To examine P2X3 receptor contributions to colon mechanosensation and hypersensitivity, electrophysiological experiments were performed using an in vitro colon-pelvic nerve preparation. Results VMRs to distension were significantly reduced in P2X3+/−and P2X3−/− mice relative to wildtype mice. Colon hypersensitivity produced by zymosan was virtually absent in P2X3−/− relative to wildtype or P2X3+/− mice. Intralumenal release of the endogenous P2X receptor ligand ATP did not differ between wildtype and P2X3−/− mice or change after intracolonic zymosan treatment. Responses of muscular and muscular-mucosal pelvic nerve afferents to mechanical stretch did not differ between P2X3−/− and wildtype mice. Both muscular and muscular-mucosal afferents in wildtype mice sensitized to application of an inflammatory soup, whereas only muscular-mucosal afferents did so in P2X3−/− mice. Conclusions These results suggest differential roles for peripheral and central P2X3 receptors in colon mechanosensory transduction and hypersensitivity. PMID:19549524

Personalized medicine in interstitial lung diseases.

PubMed

Spagnolo, Paolo; Oldham, Justin M; Jones, Mark G; Lee, Joyce S

2017-05-01

A number of recent studies have explored the possibility to apply personalized medicine to interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF), the most common and deadly of the idiopathic interstitial pneumonias. In our review, we summarize and discuss the most recent literature on personalized medicine in IPF as well as hypersensitivity pneumonitis and sarcoidosis, with emphasis on patient subgroups for which a personalized approach to disease prognostication and management may become a reality in the near future. Most of the studies that have explored the applicability of personalized medicine to ILDs have been conducted in patients with IPF. Such studies have suggested the existence of several distinct disease subgroups defined by similar genetic profiles, molecular pathways, exposures and individual lifestyles. Personalized medicine in hypersensitivity pneumonitis is in its infancy. The development and applicability of personalized medicine to sarcoidosis, on the other hand, remains problematic for several reasons, including the lack of a diagnostic gold standard, the highly variable and unpredictable disease course, particularly across patients of different ethnicities, the poor correlation between disease activity and disease severity and the lack of a validated management algorithm. A number of distinct patient subgroups have been identified in ILDs. Although available data need to be validated longitudinally, the possibility to study homogeneous groups of patients may allow prediction of disease behavior and response to treatment with dramatic clinical implications.

The search for early markers of plague: evidence for accumulation of soluble Yersinia pestis LcrV in bubonic and pneumonic mouse models of disease.

PubMed

Flashner, Yehuda; Fisher, Morly; Tidhar, Avital; Mechaly, Adva; Gur, David; Halperin, Gideon; Zahavy, Eran; Mamroud, Emanuelle; Cohen, Sara

2010-07-01

Markers of the early stages of plague, a rapidly progressing deadly disease, are crucial for enabling the onset of an effective treatment. Here, we show that V-antigen protein (LcrV) is accumulated in the serum of Yersinia pestis-infected mice before bacterial colonization of the spleen and dissemination to blood, in a model of bubonic plague. LcrV accumulation is detected earlier than that of F1 capsular antigen, an established marker of disease. In a mouse model of pneumonic plague, LcrV can be determined in the bronchoalveolar lavage fluid somewhat later than F1, but before dissemination of Y. pestis to the blood. Thus, determination of soluble LcrV is suggested as a potential useful tool for monitoring disease progression in both bubonic and pneumonic plague. Moreover, it may be of particular advantage in cases of infections with F1 nonproducing strains.

Carbamazepine-hypersensitivity: assessment of clinical and in vitro chemical cross-reactivity with phenytoin and oxcarbazepine.

PubMed Central

Pirmohamed, M; Graham, A; Roberts, P; Smith, D; Chadwick, D; Breckenridge, A M; Park, B K

1991-01-01

1. Seven patients clinically diagnosed as being hypersensitive to carbamazepine and one patient hypersensitive to both carbamazepine and oxcarbazepine have been identified. They have been compared with a control group (hereafter referred to as 'control subjects') comprising five patients on chronic carbamazepine therapy without adverse effects and 12 healthy volunteers who have never been exposed to anticonvulsants. 2. An in vitro cytotoxicity assay employing mononuclear leucocytes as target cells has been used first, to determine the ability of 10 different human livers to bioactivate carbamazepine to a cytotoxic metabolite, and secondly, to compare the cell defences of carbamazepine-hypersensitive patients and control subjects to oxidative drug metabolites generated by a murine microsomal system, using a blinded protocol. 3. With human liver microsomes, the metabolism-dependent cytotoxicity of carbamazepine increased with increasing microsomal protein concentration. At a protein concentration of 2 mg per incubation, the cytotoxicity of carbamazepine with human liver microsomes (n = 10 livers) increased from 7.2 +/- 0.8% (baseline) to 16.4 +/- 2.1% (with NADPH; P = 0.002). 4. In the presence of phenobarbitone-induced mouse microsomes and NADPH, the mean increase in cytotoxicity above the baseline with carbamazepine was significantly greater (P less than 0.001) for the cells from the carbamazepine-hypersensitive patients (7.9 +/- 0.8%) than from control subjects (2.6 +/- 0.3%). 5. In the presence of phenobarbitone-induced mouse microsomes and NADPH, there was no significant difference in cytotoxicity between the cells from carbamazepine hypersensitive patients and from control subjects in the presence of either phenytoin or oxcarbazepine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1768568

Improved reactive nanoparticles to treat dentin hypersensitivity.

PubMed

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

2018-05-01

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

Loss of central inhibition: implications for behavioral hypersensitivity after contusive spinal cord injury in rats.

PubMed

Berrocal, Yerko A; Almeida, Vania W; Puentes, Rocio; Knott, Eric P; Hechtman, Jaclyn F; Garland, Mary; 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.

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

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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Performance of genetic risk factors in prediction of trichloroethylene induced hypersensitivity syndrome

PubMed Central

Dai, Yufei; Chen, Ying; Huang, Hanlin; Zhou, Wei; Niu, Yong; Zhang, Mingrong; Bin, Ping; Dong, Haiyan; Jia, Qiang; Huang, Jianxun; Yi, Juan; Liao, Qijun; Li, Haishan; Teng, Yanxia; Zang, Dan; Zhai, Qingfeng; Duan, Huawei; Shen, Juan; He, Jiaxi; Meng, Tao; Sha, Yan; Shen, Meili; Ye, Meng; Jia, Xiaowei; Xiang, Yingping; Huang, Huiping; Wu, Qifeng; Shi, Mingming; Huang, Xianqing; Yang, Huanming; Luo, Longhai; Li, Sai; Li, Lin; Zhao, Jinyang; Li, Laiyu; Wang, Jun; Zheng, Yuxin

2015-01-01

Trichloroethylene induced hypersensitivity syndrome is dose-independent and potentially life threatening disease, which has become one of the serious occupational health issues and requires intensive treatment. To discover the genetic risk factors and evaluate the performance of risk prediction model for the disease, we conducted genomewide association study and replication study with total of 174 cases and 1761 trichloroethylene-tolerant controls. Fifty seven SNPs that exceeded the threshold for genome-wide significance (P < 5 × 10−8) were screened to relate with the disease, among which two independent SNPs were identified, that is rs2857281 at MICA (odds ratio, 11.92; Pmeta = 1.33 × 10−37) and rs2523557 between HLA-B and MICA (odds ratio, 7.33; Pmeta = 8.79 × 10−35). The genetic risk score with these two SNPs explains at least 20.9% of the disease variance and up to 32.5-fold variation in inter-individual risk. Combining of two SNPs as predictors for the disease would have accuracy of 80.73%, the area under receiver operator characteristic curves (AUC) scores was 0.82 with sensitivity of 74% and specificity of 85%, which was considered to have excellent discrimination for the disease, and could be considered for translational application for screening employees before exposure. PMID:26190474

Cutaneous and systemic hypersensitivity reactions to metallic implants.

PubMed

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

2011-01-01

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

Burning mouth syndrome: the role of contact hypersensitivity.

PubMed

Marino, R; Capaccio, P; Pignataro, L; Spadari, F

2009-05-01

Burning mouth syndrome is a burning sensation or stinging disorder affecting the oral mucosa in the absence of any clinical signs or mucosal lesions. Some studies have suggested that burning mouth syndrome could be caused by the metals used in dental prostheses, as well as by acrylate monomers, additives and flavouring agents, although others have not found any aetiologic role for hypersensitivity to dental materials. To evaluate the extent and severity of adverse reactions to dental materials in a group of patients with burning mouth syndrome, and investigate the possible role of contact allergy in its pathogenesis. We prospectively studied 124 consecutive patients with burning mouth syndrome (108 males; mean age 57 years, range 41-83), all of whom underwent allergen patch testing between 2004 and 2007. Sixteen patients (13%) showed positive patch test reactions and were classified as having burning mouth syndrome type 3 or secondary burning mouth syndrome (Lamey's and Scala's classifications). Although we did not find any significant association between the patients and positive patch test reactions, it would be advisable to include hypersensitivity to dental components when evaluating patients experiencing intermittent oral burning without any clinical signs.

Point mutant mice with hypersensitive alpha 4 nicotinic receptors show dopaminergic deficits and increased anxiety.

PubMed

Labarca, C; Schwarz, J; Deshpande, P; Schwarz, S; Nowak, M W; Fonck, C; Nashmi, R; Kofuji, P; Dang, H; Shi, W; Fidan, M; Khakh, B S; Chen, Z; Bowers, B J; Boulter, J; Wehner, J M; Lester, H A

2001-02-27

Knock-in mice were generated that harbored a leucine-to-serine mutation in the alpha4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor display dominant neonatal lethality. These mice have a severe deficit of dopaminergic neurons in the substantia nigra, possibly because the hypersensitive receptors are continuously activated by normal extracellular choline concentrations. A strain that retains the neo selection cassette in an intron has reduced expression of the hypersensitive receptor and is viable and fertile. The viable mice display increased anxiety, poor motor learning, excessive ambulation that is eliminated by very low levels of nicotine, and a reduction of nigrostriatal dopaminergic function upon aging. These knock-in mice provide useful insights into the pathophysiology of sustained nicotinic receptor activation and may provide a model for Parkinson's disease.

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

PubMed Central

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

2014-01-01

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

Rehabilitation modality and onset differentially influence whisker sensory hypersensitivity after diffuse traumatic brain injury in the rat.

PubMed

Thomas, Theresa Currier; Stockhausen, Ellen Magee; Law, L Matthew; Khodadad, Aida; Lifshitz, Jonathan

2017-01-01

As rehabilitation strategies advance as therapeutic interventions, the modality and onset of rehabilitation after traumatic brain injury (TBI) are critical to optimize treatment. Our laboratory has detected and characterized a late-onset, long-lasting sensory hypersensitivity to whisker stimulation in diffuse brain-injured rats; a deficit that is comparable to visual or auditory sensory hypersensitivity in humans with an acquired brain injury. We hypothesize that the modality and onset of rehabilitation therapies will differentially influence sensory hypersensitivity in response to the Whisker Nuisance Task (WNT) as well as WNT-induced corticosterone (CORT) stress response in diffuse brain-injured rats and shams. After midline fluid percussion brain injury (FPI) or sham surgery, rats were assigned to one of four rehabilitative interventions: (1) whisker sensory deprivation during week one or (2) week two or (3) whisker stimulation during week one or (4) week two. At 28 days following FPI and sham procedures, sensory hypersensitivity was assessed using the WNT. Plasma CORT was evaluated immediately following the WNT (aggravated levels) and prior to the pre-determined endpoint 24 hours later (non-aggravated levels). Deprivation therapy during week two elicited significantly greater sensory hypersensitivity to the WNT compared to week one (p < 0.05), and aggravated CORT levels in FPI rats were significantly lower than sham levels. Stimulation therapy during week one resulted in low levels of sensory hypersensitivity to the WNT, similar to deprivation therapy and naïve controls, however, non-aggravated CORT levels in FPI rats were significantly higher than sham. These data indicate that modality and onset of sensory rehabilitation can differentially influence FPI and sham rats, having a lasting impact on behavioral and stress responses to the WNT, emphasizing the necessity for continued evaluation of modality and onset of rehabilitation after TBI.

Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague

PubMed Central

Stasulli, Nikolas M.; Eichelberger, Kara R.; Price, Paul A.; Pechous, Roger D.; Montgomery, Stephanie A.; Parker, Joel S.

2015-01-01

ABSTRACT During pneumonic plague, the bacterium Yersinia pestis elicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence are poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and transcriptome sequencing (RNA-seq) analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are downregulated in the center of lung lesions compared to the periphery. Probing for the bacterial factor(s) important for the alteration in neutrophil survival, we show both in vitro and in vivo that Y. pestis increases neutrophil survival in a manner that is dependent on the type III secretion system effector YopM. This research explores the complexity of spatially distinct host-microbe interactions and emphasizes the importance of cell relevance in assays in order to fully understand Y. pestis virulence. PMID:26463167

Seven Steps to the Diagnosis of NSAIDs Hypersensitivity: How to Apply a New Classification in Real Practice?

PubMed Central

Makowska, Joanna S.

2015-01-01

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. PMID:25749768

Evaluation of basophil activation test in suspected food hypersensitivity.

PubMed

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

2017-07-01

Food hypersensitivity is characterized by a wide range of symptoms. The relationship between symptoms and food is more frequently suspected than objectively proven. Basophil activation test (BAT) is based on the evaluation of activation markers on blood basophils in vitro stimulated with drugs or allergens. The aim of the study was to evaluate the usefulness of BAT when introduced in the routine work-up of suspected food hypersensitivity. BAT was requested in subjects with food adverse reactions when a discrepancy existed among history and skin prick test (SPT) and/or specific IgE. Data from 150 subjects were analysed using CD63 as basophil activation marker. Thirty controls were evaluated for cut-offs. Immunoblots was performed with the sera of representative subjects positive for BAT and negative for SPT and sIgE. 1,024 BAT were carried out, the agreement (positive/positive and negative/negative) was 78.5% for BAT vs. SPT and 78.3% for BAT vs. IgE. Atopic patients, but not atopic controls, more frequently had a positive BAT than non-atopic patients (P < 0.0001). Among subjects with positive BAT, those with negative sIgE had lower total IgE, P = 0.001. Nearly 23.3% of all subjects had positive BAT (for at least one tested food) and both negative sIgE and SPT. Immunoblots revealed the presence of sIgE for the tested foods in representative patients with positive BAT, negative SPT and sIgE. Introduction of BAT in routine of food hypersensitivity, limited to subjects with a discrepancy between history and traditional tests, might be useful particularly when total IgE are low. © 2015 International Clinical Cytometry Society. © 2015 International Clinical Cytometry Society.

Multinational experience with hypersensitivity drug reactions in Latin America.

PubMed

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

2014-09-01

Epidemiologic drug allergy data from Latin America are scarce, and there are no studies on specific procedures focusing on this topic in Latin America. To assess the clinical characteristics and management of hypersensitivity drug reactions in different Latin American countries. An European Network of Drug Allergy questionnaire survey was implemented in 22 allergy units in 11 Latin American countries to report on consecutive patients who presented with a suspected hypersensitivity drug reaction. Each unit used its own protocols to investigate patients. Included were 868 hypersensitivity drug reactions in 862 patients (71% of adults and elderly patients were women and 51% of children were girls, P = .0001). Children presented with less severe reactions than adults and elderly patients (P < .0001). Urticaria and angioedema accounted for the most frequent clinical presentations (71%), whereas anaphylaxis was present in 27.3% of cases. There were no deaths reported. Nonsteroidal anti-inflammatory drugs (52.3%), β-lactam antibiotics (13.8%), and other antibiotics (10.1%) were the drugs used most frequently. Skin prick tests (16.7%) and provocation tests (34.2%) were the study procedures most commonly used. A large proportion of patients were treated in the emergency department (62%) with antihistamines (68%) and/or corticosteroids (53%). Only 22.8% of patients presenting with anaphylaxis received epinephrine. Nonsteroidal anti-inflammatory drugs and antibiotics were the drugs used in at least 75% of patients. More than half the reactions were treated in the emergency department, whereas epinephrine was administered in fewer than 25% of patients with anaphylaxis. Dissemination of guidelines for anaphylaxis among primary and emergency department physicians should be encouraged. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Modified criteria for carotid sinus hypersensitivity are associated with increased mortality in a population-based study

PubMed Central

McDonald, Claire; Pearce, Mark S.; Newton, Julia L.; Kerr, Simon R.J.

2016-01-01

Abstract Aims Carotid sinus hypersensitivity (CSH) is arbitrarily defined as ≥3 s asystole or vasodepression of ≥50 mmHg in response to carotid sinus massage (CSM). Using this definition, 39% of older people meet the criteria for CSH. It has been suggested that current criteria are too sensitive. Krediet et al. [The history of diagnosing carotid sinus hypersensitivity: why are the current criteria too sensitive? Europace 2011;13:14–22] and Kerr et al. [Carotid sinus hypersensitivity in asymptomatic older persons: implications for diagnosis of syncope and falls. Arch Intern Med 2006;166:515–20] have proposed modified criteria. This population-based study aimed to compare the prevalence of CSH defined according to standard, Krediet and Kerr criteria, and to establish if CSH defined according these criteria is associated with all-cause mortality. Methods and results A total of 272 community-dwelling people aged ≥65 were recruited at random. Carotid sinus massage was performed for 5 s in supine and head-up positions. Heart rate and blood pressure response were recorded using an electrocardiogram and photoplethysmography. Cox regression analysis was used to examine the association between each definition of CSH and all-cause mortality. The prevalence of CSH defined according to standard, Krediet, and Kerr criteria was 39, 52, and 10%, respectively. Seventy-one participants died over a mean follow-up of 8.6 years (SD 2.1). Carotid sinus hypersensitivity defined according to standard and Krediet criteria was not associated with survival. Carotid sinus hypersensitivity defined according to Kerr criteria was associated with all-cause mortality independent of age and sex [hazard ratio (HR) 2.023 (95% confidence interval (95% CI) 1.131–3.618) P = 0.018)]. This remained significant after adjusting for cardiovascular risk factors [HR 2.174 (1.075–3.900) P = 0.009]. Conclusion Carotid sinus hypersensitivity defined according to Kerr criteria is associated with

Optimization and simplification of the Allergic and Hypersensitivity conditions classification for the ICD-11.

PubMed

Tanno, L K; Calderon, M A; Demoly, P

2016-05-01

Since 2013, an international collaboration of Allergy Academies, including first the World Allergy Organization (WAO), the American Academy of Allergy Asthma and Immunology (AAAAI), and the European Academy of Allergy and Clinical Immunology (EAACI), and then the American College of Allergy, Asthma and Immunology (ACAAI), the Latin American Society of Allergy, Asthma and Immunology (SLAAI), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI), has spent tremendous efforts to have a better and updated classification of allergic and hypersensitivity conditions in the forthcoming International Classification of Diseases (ICD)-11 version by providing evidences and promoting actions for the need for changes. The latest action was the implementation of a classification proposal of hypersensitivity/allergic diseases built by crowdsourcing the Allergy Academy leaderships. Following bilateral discussions with the representatives of the ICD-11 revision, a face-to-face meeting was held at the United Nations Office in Geneva and a simplification process of the hypersensitivity/allergic disorders classification was carried out to better fit the ICD structure. We are here presenting the end result of what we consider to be a model of good collaboration between the World Health Organization and a specialty. We strongly believe that the outcomes of all past and future actions will impact positively the recognition of the allergy specialty as well as the quality improvement of healthcare system for allergic and hypersensitivity conditions worldwide. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In Vivo Cysteinyl Leukotriene Release in Allergic and Nonallergic Immediate Hypersensitivity Reactions during Anesthesia.

PubMed

Laroche, Dominique; Léturgie, Pierre; Mariotte, Delphine; Ollivier, Yann; Hanouz, Jean-Luc; Le Mauff, Brigitte; Parienti, Jean-Jacques

2017-05-01

Immediate hypersensitivity reactions occurring during anesthesia are classified as allergic when skin tests and mast cell tryptase are positive and as nonallergic when negative results are obtained. Cysteinyl leukotrienes (cysLTs) are potent mediators synthesized by mast cell and eosinophil that induce bronchial constriction. They could play a role in hypersensitivity reactions. cysLT C4, D4, and E4 concentrations were measured by a competition immunoassay in serial plasma samples obtained prospectively from 21 anesthetized controls and retrospectively from 34 patients who reacted at induction of anesthesia (24 with allergic and 10 with nonallergic reactions). In controls, the median (interquartile range) cysLT concentration was 0.83 (0.69 to 1.02) μg/l before anesthesia and was unchanged 30 min, 6 h, and 24 h afterward. In the patients with allergic reactions, the values were highly increased 30 to 60 min after the reaction (17.9 [7.8 to 36.0] μg/l), while the patients with nonallergic reactions had less increased values (7.3 [3.0 to 11.5] μg/l). The difference between the three groups was significant (P < 0.0001). Increased values persisted during the 24 h of observation. Concentrations were significantly higher in patients with bronchospasm (P = 0.016). cysLTs appear to be an important mediator of allergic and nonallergic immediate hypersensitivity reactions. These findings might open a new field for management of patients with hypersensitivity reactions, especially nonallergic ones.

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

Current use of Australian snake antivenoms and frequency of immediate-type hypersensitivity reactions and anaphylaxis.

PubMed

Isbister, Geoffrey K; Brown, Simon G; MacDonald, Ellen; White, Julian; Currie, Bart J

2008-04-21

To investigate current use of Australian snake antivenoms and the frequency and severity of immediate-type hypersensitivity reactions. Nested prospective cohort study as part of the Australian Snakebite Project. Patients receiving snake antivenom in Australian hospitals between 1 January 2002 and 30 November 2007. The use of CSL Limited antivenom; frequency and severity of hypersensitivity reactions to antivenom; premedication and treatment of these reactions. Snake antivenom was administered to 195 patients, mostly for venom-induced consumption coagulopathy (145 patients, 74%), followed by non-specific systemic effects (12%), neurotoxicity (5%) and myotoxicity (4%). Antivenom was given to nine patients (5%) without evidence of envenoming or who were bitten by a species of snake for which antivenom is not required. The commonest antivenoms used were brown snake (46%), tiger snake (30%) and polyvalent (11%). The median dose was four vials (interquartile range, 2-5 vials), and 24 patients received two different types of antivenom. Immediate-type hypersensitivity reactions occurred in 48 patients (25%); 21 satisfied our definition of anaphylaxis, with 11 moderate and 10 severe cases, including nine in which patients were hypotensive. The remaining 27 reactions were mild (skin only). Adrenaline was used in 26 cases with good effect. The frequency of reactions to tiger snake (41%) and polyvalent (41%) antivenoms was higher than that to brown snake antivenom (10%). Hypersensitivity reactions occurred in 11 of 40 patients receiving any form of premedication (28%) and in 2 of 11 given adrenaline for premedication (18%) versus 20 of 86 not receiving premedication (23%). Antivenom was used appropriately, and most commonly for coagulopathy. Hypersensitivity reactions were common, but most were not severe. The discretionary use of premedication was not associated with any reduction in reactions.

Impact of Prophylactic Conversion to an Extended Infusion Schedule to Prevent Hypersensitivity Reactions in Ovarian Cancer Patients during Carboplatin Retreatment

PubMed Central

O’Cearbhaill, Roisin; Zhou, Qin; Iasonos, Alexia; Hensley, Martee L.; Tew, William P.; Aghajanian, Carol; Spriggs, David R.; Lichtman, Stuart M.; Sabbatini, Paul J.

2015-01-01

Objective Repeated exposure to carboplatin can lead to hypersensitivity reactions during retreatment with carboplatin. This may prevent its further use in platinum-sensitive ovarian cancer patients. At our institution, an increasing proportion of patients are prophylactically converted to an extended schedule of infusion after 8 cycles of carboplatin. We sought to determine whether an incrementally increasing, extended 3-hour infusion of carboplatin was associated with a lower rate of hypersensitivity reactions compared to the standard 30-minute schedule in sequentially treated patients. Methods We performed a retrospective electronic medical record review of patients with recurrent ovarian cancer retreated with carboplatin at our institution from 01/98–12/08. Results Seven hundred seventy-seven patients with relapsed ovarian, fallopian tube, or primary peritoneal cancer were retreated with carboplatin and met study inclusion criteria. Of these, 117 (17%) developed hypersensitivity reactions during second-line or greater carboplatin-based treatment for recurrent disease. Only 6 (3.4%) of the 174 patients who received the extended schedule developed hypersensitivity reactions (0% grade 4; 1.7% grade 3) compared to 111 (21%) of 533 patients in the standard schedule group (12% grade 4; 77% grade 3). The first hypersensitivity episode occurred after a median of 16 platinum (carboplatin and cisplatin) treatments in the extended group compared to 9 in the standard group. Using the Fisher-exact test, there was an association with a reduced incidence of hypersensitivity reactions with the extended infusion schedule (P<0.001). Conclusion Our data suggest appropriate premedication and prophylactic conversion to an extended infusion during carboplatin retreatment may reduce hypersensitivity reactions. PMID:19944454

Delayed-type hypersensitivity reactions induced by proton pump inhibitors: A clinical and in vitro T-cell reactivity study.

PubMed

Lin, C-Y; Wang, C-W; Hui, C-Y R; Chang, Y-C; Yang, C-H; Cheng, C-Y; Chen, W-W; Ke, W-M; Chung, W-H

2018-01-01

Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed-type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T-cell reactivity to PPI in PPI-related DHR patients. We retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities. There were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay. PPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Tinnitus and other auditory problems - occupational noise exposure below risk limits may cause inner ear dysfunction.

PubMed

Lindblad, Ann-Cathrine; Rosenhall, Ulf; Olofsson, Åke; Hagerman, Björn

2014-01-01

The aim of the investigation was to study if dysfunctions associated to the cochlea or its regulatory system can be found, and possibly explain hearing problems in subjects with normal or near-normal audiograms. The design was a prospective study of subjects recruited from the general population. The included subjects were persons with auditory problems who had normal, or near-normal, pure tone hearing thresholds, who could be included in one of three subgroups: teachers, Education; people working with music, Music; and people with moderate or negligible noise exposure, Other. A fourth group included people with poorer pure tone hearing thresholds and a history of severe occupational noise, Industry. Ntotal = 193. The following hearing tests were used: - pure tone audiometry with Békésy technique, - transient evoked otoacoustic emissions and distortion product otoacoustic emissions, without and with contralateral noise; - psychoacoustical modulation transfer function, - forward masking, - speech recognition in noise, - tinnitus matching. A questionnaire about occupations, noise exposure, stress/anxiety, muscular problems, medication, and heredity, was addressed to the participants. Forward masking results were significantly worse for Education and Industry than for the other groups, possibly associated to the inner hair cell area. Forward masking results were significantly correlated to louder matched tinnitus. For many subjects speech recognition in noise, left ear, did not increase in a normal way when the listening level was increased. Subjects hypersensitive to loud sound had significantly better speech recognition in noise at the lower test level than subjects not hypersensitive. Self-reported stress/anxiety was similar for all groups. In conclusion, hearing dysfunctions were found in subjects with tinnitus and other auditory problems, combined with normal or near-normal pure tone thresholds. The teachers, mostly regarded as a group exposed to noise

The Effect of Various Concentrations of Nitrous Oxide and Oxygen on the Hypersensitive Gag Reflex.

PubMed

De Veaux, Candace K E; Montagnese, Thomas A; Heima, Masahiro; Aminoshariae, Anita; Mickel, Andre

2016-01-01

The purpose of this study was to compare the effectiveness of various concentrations of N 2 O/O 2 on obtunding a hypersensitive gag reflex. We hypothesized that the administration of nitrous oxide and oxygen would obtund a hypersensitive gag reflex enough to allow a patient to tolerate the placement and holding of a digital x-ray sensor long enough to obtain a dental radiograph. Volunteers claiming to have a hypersensitive gag reflex were first screened to validate their claim and then tested by placing a size 2 digital x-ray sensor in the position for a periapical radiograph of the right mandibular molar area and holding it in place for 10 seconds. Subjects were first tested using room air only, then 30%, 50%, or 70% nitrous oxide until they were able to tolerate the sensor without gagging or discomfort. A visual analog scale was used for subjective responses, and other statistical tests were used to analyze the results. We found that for some subjects, 30% nitrous oxide was sufficient; for others, 50% was needed; and for the remainder of the subjects, 70% was sufficient to tolerate the test. Using a combination of 70% nitrous oxide and 30% oxygen allowed all patients claiming to have a hypersensitive gag reflex to tolerate the placement and holding of a digital x-ray sensor long enough to take a periapical radiograph.

Should patients with risk factors be tested for hypersensitivity to contrast media: a prospective study.

PubMed

Tepetam, Fatma Merve; Çiftaslan, Nezihe; Oruç, Özlem; Duman, Dildar; Ağca, Meltem; Bulut, İsmet; Çolakoğlu, Bahattin

2016-08-01

Previous hypersensitivity reactions to contrast media (CM), atopy, atopic disease, drug allergy, and age (20-29 or >55) are risk factors for CM hypersensitivity reactions. Our aim was to evaluate whether these risk factors should prompt skin testing for diagnosing CM allergy. The study was conducted among patients referred for allergy testing with CM. Skin tests were performed with non ionic or gadolinium CM, recommended by a radiologist. After completion of tests patients were telephonically queried on their symptoms of reactions. 151 risk patients (53 men, 98 women; mean age 55.2) were included in the study. Only 13 (9 %) had a history of hypersensitivity reaction to CM. Compared with the other patients, atopy was significantly more common in patients with a history of CM hypersensitivity reactions. Female gender and mean age were also higher, but not significant. All of the tests with CMs were negative. Only one patient reported urticaria within 1-2 min after administration of CM (telephonically). Atopy can increase the risk of CM allergy. However, skin tests with CMs may be inefficient, unnecessary, and time-consuming, except in cases with a history of CM allergy. Premedication protocols appear to be beneficial in patients with a history of CM allergy and cannot be recommended for patients with well-controlled asthma, rhinitis, atopic dermatitis or history of drug allergy.

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

PubMed

Schalock, Peter C; Thyssen, Jacob P

2013-01-01

Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated. Diagnostic criteria for hypersensitivity reactions after metallic device implantation are evaluated in this study by a multinational group of patch testers using Thyssen's previously published criteria. A total of 119 dermatologists at the 2012 European Contact Dermatitis Society and 2013 American Contact Dermatitis Society meetings answered a survey regarding their opinions on topics relating to metal hypersensitivity. Four major and 5 minor diagnostic criteria emerged. Approximately 80% of respondents found the following criteria useful (major criteria): chronic dermatitis beginning weeks to months after metallic implantation, eruption overlying the metal implant, positive patch test to a metal component of the implant, and complete clearing after removal of the potentially allergenic implant. Minor criteria (<61% of respondents) were as follows: systemic allergic dermatitis reaction, therapy-resistant dermatitis, morphology consistent with dermatitis, histology consistent with allergic contact dermatitis, and a positive in vitro test to metals (eg, lymphocyte transformation test). In the challenging situation such as a symptomatic or failing orthopedic device, applying these 4 major criteria and the 5 supportive minor criteria may be useful for guiding decision making.

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. © 2015 The Association of Anaesthetists of Great Britain and Ireland.

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

Dental Erosion and Dentin Hypersensitivity among Adult Asthmatics and Non-asthmatics Hospital-based: A Preliminary Study.

PubMed

Farag, Zahra Hassan Abdelaziz; Awooda, Elhadi Mohieldin

2016-01-01

Asthma is a chronic inflammatory condition affecting the airways leading to spasm and swelling of the airways. The medications taken for the treatment of asthma can result in dental erosion and dentin hypersensitivity. The aims of this study were to investigate the severity of dental erosion amongst adult asthmatics according to: gender, type and duration of medication taken and to compare dental erosion and dentin hypersensitivity between asthmatics and non-asthmatics. Comparative, cross-sectional hospital based study among 40 asthmatics (M=15 & F=25) and 40 non-asthmatics (M=18 & F=22) in the age range of 18-60 year selected purposefully from Al-Shaab Teaching Hospital in Khartoum city. The Basic Erosive Wear Index was used for dental erosion assessment. Dentine hypersensitivity was determined by giving ice cold water and rated using the Visual Analogue Scale. Chi-square and Student's t-test were used for statistical analysis with P value ≤.05. There was an association between severity of dental erosion and presence of asthma (P=0.03), where asthmatics had a higher degree of erosion (moderate and severe) and non-asthmatics a lower degree. No significant association was found between dental erosion and gender, type and duration of medication among asthmatics group. A statistically significant difference was revealed in the degree of dentin hypersensitivity (P=0.00) among asthmatics (35.13%) and non-asthmatics (14.13%). Asthmatic patients had a higher degree of dental erosion and dentin hypersensitivity compared to non-asthmatics. Among asthmatic patients there was no association between severity of dental erosion and gender, type and duration medication was taken for.

Signal interactions between nitric oxide and reactive oxygen intermediates in the plant hypersensitive disease resistance response.

PubMed

Delledonne, M; Zeier, J; Marocco, A; Lamb, C

2001-11-06

Nitric oxide (NO) and reactive oxygen intermediates (ROIs) play key roles in the activation of disease resistance mechanisms both in animals and plants. In animals NO cooperates with ROIs to kill tumor cells and for macrophage killing of bacteria. Such cytotoxic events occur because unregulated NO levels drive a diffusion-limited reaction with O(2)(-) to generate peroxynitrite (ONOO(-)), a mediator of cellular injury in many biological systems. Here we show that in soybean cells unregulated NO production at the onset of a pathogen-induced hypersensitive response (HR) is not sufficient to activate hypersensitive cell death. The HR is triggered only by balanced production of NO and ROIs. Moreover, hypersensitive cell death is activated after interaction of NO not with O(2)- but with H(2)O(2) generated from O(2)(-) by superoxide dismutase. Increasing the level of O(2)(-) reduces NO-mediated toxicity, and ONOO(-) is not a mediator of hypersensitive cell death. During the HR, superoxide dismutase accelerates O(2)(-) dismutation to H(2)O(2) to minimize the loss of NO by reaction with O(2)(-) and to trigger hypersensitive cell death through NO/H(2)O(2) cooperation. However, O(2)(-) rather than H(2)O(2) is the primary ROI signal for pathogen induction of glutathione S-transferase, and the rates of production and dismutation of O(2)(-) generated during the oxidative burst play a crucial role in the modulation and integration of NO/H(2)O(2) signaling in the HR. Thus although plants and animals use a similar repertoire of signals in disease resistance, ROIs and NO are deployed in strikingly different ways to trigger host cell death.

Mechanism of auditory hypersensitivity in human autism using autism model rats.

PubMed

Ida-Eto, Michiru; Hara, Nao; Ohkawara, Takeshi; Narita, Masaaki

2017-04-01

Auditory hypersensitivity is one of the major complications in autism spectrum disorder. The aim of this study was to investigate whether the auditory brain center is affected in autism model rats. Autism model rats were prepared by prenatal exposure to thalidomide on embryonic day 9 and 10 in pregnant rats. The superior olivary complex (SOC), a complex of auditory nuclei, was immunostained with anti-calbindin d28k antibody at postnatal day 50. In autism model rats, SOC immunoreactivity was markedly decreased. Strength of immunostaining of SOC auditory fibers was also weak in autism model rats. Surprisingly, the size of the medial nucleus of trapezoid body, a nucleus exerting inhibitory function in SOC, was significantly decreased in autism model rats. Auditory hypersensitivity may be, in part, due to impairment of inhibitory processing by the auditory brain center. © 2016 Japan Pediatric Society.

Effect of Prophylactic Extended-Infusion Carboplatin on Incidence of Hypersensitivity Reactions in Patients with Ovarian, Fallopian Tube, or Peritoneal Carcinomas.

PubMed

Pasternak, Amy L; Link, Nicholas A; Richardson, Carolyn M; Rose, Peter G

2016-07-01

To determine whether extended-infusion carboplatin, initiated at approximately the eighth cumulative carboplatin cycle and prior to development of carboplatin hypersensitivity, reduces the incidence of carboplatin hypersensitivity reactions in patients with ovarian, fallopian tube, or peritoneal cancer. Retrospective chart review. Large integrated health system. A total of 326 patients with ovarian, fallopian tube, or primary peritoneal cancer who received at least eight cumulative cycles of carboplatin between January 2007 and September 2014 were included. Of these, 161 patients received all doses of carboplatin infused over 30 or 60 minutes (standard-infusion group [total of 1317 carboplatin cycles]), and 165 patients received the 3-hour extended infusion of carboplatin administered at approximately the eighth cumulative cycle and prior to development of a hypersensitivity reaction (extended-infusion group [total of 1527 carboplatin cycles]). Baseline characteristics were similar between the groups, except significantly more patients in the extended-infusion group received triple premedication therapy prior to infusion (p<0.001). Hypersensitivity reactions occurred in 64 patients (40%) who received standard-infusion carboplatin and 40 patients (24.2%) who received extended-infusion carboplatin (p=0.0027). The median cycle of hypersensitivity reaction development did not differ significantly between the groups: 9 cycles in patients who received standard-infusion versus 11 cycles in patients who received extended-infusion carboplatin (p=0.06). Through regression analysis, the premedication regimen received prior to carboplatin infusion was the only variable significantly associated with hypersensitivity reactions (odds ratio 0.59, 95% confidence interval 0.36-0.97, p=0.038). Patients who received extended-infusion carboplatin experienced a lower incidence of hypersensitivity reactions than patients who received standard-infusion carboplatin, which may be attributed

From the Children’s Oncology Group: Evidence-based recommendations for PEG-asparaginase nurse monitoring, hypersensitivity reaction management, and patient/family education

PubMed Central

Woods, Deborah; Winchester, Kari; Towerman, Alison; Gettinger, Katie; Carey, Christina; Timmermann, Karen; Langley, Rachel; Browne, Emily

2017-01-01

PEG-aspariginase is a backbone chemotherapy agent in pediatric acute lymphoblastic leukemia and in some non-Hodgkin lymphoma therapies. Nurses lack standardized guidelines for monitoring patients receiving PEG-asparaginase and for educating patients/families about hypersensitivity reaction risks. An electronic search of six databases using publication years 2000–2015 and multiple professional organizations and clinical resources was conducted. Evidence sources were reviewed for topic applicability. Each of the final 23 sources was appraised by two team members. The GRADE system was used to assign a quality and strength rating for each recommendation. Multiple recommendations were developed: four relating to nurse monitoring of patients during and after drug administration, eight guiding hypersensitivity reaction management, and four concerning patient/family educational content. These strong recommendations were based on moderate, low, or very-low quality evidence. Several recommendations relied upon generalized drug hypersensitivity guidelines. Additional research is needed to safely guide PEG-asparaginase monitoring, hypersensitivity reaction management and patient/family education. Nurses administering PEG-asparaginase play a critical role in the early identification and management of hypersensitivity reactions. PMID:28602129

Incidence of immediate hypersensitivity reaction and serum sickness following administration of Crotalidae polyvalent immune Fab antivenom: a meta-analysis.

PubMed

Schaeffer, Tammi H; Khatri, Vaishali; Reifler, Liza M; Lavonas, Eric J

2012-02-01

  Crotalidae polyvalent immune Fab (ovine) (FabAV) is commonly used in the treatment of symptomatic North American crotaline snake envenomation. When approved by the U.S. Food and Drug Administration in 2000, the incidences of immediate hypersensitivity reactions and serum sickness were reported as 0.14 and 0.18, respectively. The objective of this meta-analysis was to evaluate the incidence of immediate hypersensitivity reactions and serum sickness reported in studies of patients treated with FabAV therapy after North American crotaline envenomation.   The authors searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to September 20, 2010, for English-language medical literature and cross-referenced bibliographies of reviewed articles. The published abstracts of the major toxicology conferences were also searched. All prospective and retrospective cohort studies with patients receiving FabAV therapy for North American crotaline envenomations were eligible for data abstraction. Two content experts reviewed full-text articles and extracted relevant study design and outcome data. Proportions of immediate hypersensitivity and serum sickness for each study were analyzed in a random-effects model to produce an overall estimate of immediate hypersensitivity and serum sickness incidence associated with FabAV administration.   The literature search revealed 11 unique studies of patients who received FabAV that contained information on immediate hypersensitivity reactions and serum sickness. The meta-analysis produced a combined estimate of the incidence of immediate hypersensitivity of 0.08 (95% confidence interval [CI] = 0.05 to 0.11) and a combined estimate of the incidence of serum sickness of 0.13 (95% CI = 0.07 to 0.21).   In this systematic literature review and meta-analysis, the combined estimates of the incidence of immediate hypersensitivity reactions and serum sickness from FabAV in the treatment of symptomatic North American crotaline

Association of dentine hypersensitivity with different risk factors - a cross sectional study.

PubMed

Vijaya, V; Sanjay, Venkataraam; Varghese, Rana K; Ravuri, Rajyalakshmi; Agarwal, Anil

2013-12-01

This study was done to assess the prevalence of Dentine hypersensitivity (DH) and its associated risk factors. This epidemiological study was done among patients coming to dental college regarding prevalence of DH. A self structured questionnaire along with clinical examination was done for assessment. Descriptive statistics were obtained and frequency distribution was calculated using Chi square test at p value <0.05. Stepwise multiple linear regression was also done to access frequency of DH with different factors. The study population was comprised of 655 participants with different age groups. Our study showed prevalence as 55% and it was more common among males. Similarly smokers and those who use hard tooth brush had more cases of DH. Step wise multiple linear regression showed that best predictor for DH was age followed by habit of smoking and type of tooth brush. Most aggravating factors were cold water (15.4%) and sweet foods (14.7%), whereas only 5% of the patients had it while brushing. A high level of dental hypersensitivity has been in this study and more common among males. A linear finding was shown with age, smoking and type of tooth brush. How to cite this article: Vijaya V, Sanjay V, Varghese RK, Ravuri R, Agarwal A. Association of Dentine Hypersensitivity with Different Risk Factors - A Cross Sectional Study. J Int Oral Health 2013;5(6):88-92 .

Occupational asthma due to turpentine in art painter--case report.

PubMed

Dudek, Wojciech; Wittczak, Tomasz; Swierczyńska-Machura, Dominika; Walusiak-Skorupa, Jolanta; Pałczyński, Cezary

2009-01-01

Turpentine is a fluid obtained by distillation of wood resins containing mixture of terpens. It can act as an irritant and sensitiser. Most common health problem among workers exposed to turpentine is contact dermatitis. Little is know about turpentine to cause type I hypersensitivity reaction. We present a case of a 27-year old art painter using turpentine as a thinner for oil-based paints. She developed asthmatic reactions after 5 years of working with turpentine. A number of clinical procedures were performed, including clinical examination, routine laboratory tests, total serum IgE, skin prick tests to common aeroallergens, metal salts, oil-based paints and balsamic turpentine, resting spirometry test, histamine challenge, and a single-blind, placebo-controlled specific inhalation challenge with balsamic turpentine. Clinical findings and laboratory test results were normal but a significant bronchial hyperreactivity was found. During the specific challenge, dyspnoea and decreased forced expiratory volume (FEV1) were observed in late phase of asthmatic reaction. An increased proportion of eosinophils in induced sputum could also be noted 24 h after the challenge. Positive clinical response to the specific challenge as well as the morphological changes found in induced sputum served as the basis for diagnosing occupational asthma. To our knowledge, this is the first well-documented case of turpentine-induced occupational asthma.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-10-01

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

T regulatory cells in contact hypersensitivity.

PubMed

Cavani, Andrea

2008-08-01

The review summarizes the recent investigations focused on T regulatory cells in hapten diseases. Multiple mechanisms ensure tolerance to small chemicals penetrating the skin. Among these, specific T regulatory cells play a major role in controlling harmful immune responses to environmental antigens. Most of the T regulatory cells involved in this process belongs to the CD4 subset and suppress hapten-specific immune response through the release of IL-10 and through direct interaction with effector T cells, blocking their function. Methods for in-vitro and in-vivo expansion of specific T regulatory cells may represent an innovative approach for the cure of contact hypersensitivity.

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. © 2015 The Author(s) Published by S. Karger AG, Basel.

Characterization of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database.

PubMed

Suwankesawong, Wimon; Saokaew, Surasak; Permsuwan, Unchalee; Chaiyakunapruk, Nathorn

2014-12-24

Andrographis paniculata (andrographis) is one of the herbal products that are widely used for various indications. Hypersensitivity reactions have been reported among subjects receiving Andrographis paniculata in Thailand. Understanding of characteristics of patients, adverse events, and clinical outcomes is essential for ensuring population safety.This study aimed to describe the characteristics of hypersensitivity reactions reported in patients receiving andrographis containing products in Thailand using national pharmacovigilance database. Thai Vigibase data from February 2001 to December 2012 involving andrographis products were used. This database includes the reports submitted through the spontaneous reporting system and intensive monitoring programmes. The database contained patient characteristic, adverse events associated with andrographis products, and details on seriousness, causality, and clinical outcomes. Case reports were included for final analysis if they met the inclusion criteria; 1) reports with andrographis being the only suspected cause, 2) reports with terms consistent with the constellation of hypersensitivity reactions, and 3) reports with terms considered critical terms according to WHO criteria. Descriptive statistics were used. A total of 248 case reports of andrographis-associated adverse events were identified. Only 106 case reports specified andrographis herbal product as the only suspected drug and reported at least one term consistent with constellation of hypersensitivity reactions. Most case reports (89%) came from spontaneous reporting system with no previously documented history of drug allergy (88%). Of these, 18 case reports were classified as serious with 16 cases requiring hospitalization. For final assessment, the case reports with terms consistent with constellation of hypersensitivity reactions and critical terms were included. Thirteen case reports met such criteria including anaphylactic shock (n = 5), anaphylactic

Identification of risk factors of severe hypersensitivity reactions in general anaesthesia.

PubMed

Mirone, Corrado; Preziosi, Donatella; Mascheri, Ambra; Micarelli, Gianluigi; Farioli, Laura; Balossi, Luca G; Scibilia, Joseph; Schroeder, Jan; Losappio, Laura M; Aversano, Maria G; Stafylaraki, Chrysi; Nichelatti, Michele; Pastorello, Elide A

2015-01-01

Hypersensitivity reactions to anaesthetic agents are rare but often severe, with a mortality ranging from 4 to 9% in IgE-mediated events. Identification of the risk factors may contribute to limit the incidence of these reactions. The aim of our study was to search for possible risk factors of severe perioperative hypersensitivity reactions in our study population. For this study we retrospectively reviewed data from 193 patients who experienced drug hypersensitivity reactions during general anaesthesia. The diagnostic protocol consisted of 1) history of the reaction, 2) measurement of serum baseline tryptase and specific IgE-assays for latex, beta-lactams and succinylcholine, 3) skin tests for the agents listed in the anaesthesia chart and for others likely to be safe for future use, latex, and others medications administered during the perioperative period (i.e. antibiotics), 4) subdivision of our patients on the basis of two criteria: a) grade of severity of clinical reactions according to the Ring and Messmer classification; b) results of skin tests and/or serum specific IgE-assays. One hundred of 193 patients had reactions of grade I, 32/193 patients had reactions of grade II, 55/193 patients had reactions of grade III and 6/193 patients had reactions of grade IV. A diagnosis of IgE-mediated reaction was established in 55 cases (28.50%); the most common causes were neuromuscular blocking agents, followed by latex and beta-lactams. Severe reactions were associated with older age (p = 0.025), asthma (p = 0.042), history of hypertension (p = 0.001), intake of serum angiotensin converting enzyme inhibitor medication (p = 0.012) or serum angiotensin II antagonist (p = 0.033), higher levels of basal tryptase (p = 0.0211). Cardiovascular symptoms (p = 0.006) and history of hypersensitivity to antibiotics (p = 0.029) were more frequently reported in IgE-mediated reactions. We confirmed the relevance of several clinical features as risk

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.

Chronic lymphadenopathic toxoplasmosis. A case with marked hyperglobulinemia and impaired delayed hypersensitivity responses during active infection.

PubMed

Sheagren, J N; Lunde, M N; Simon, H B

1976-02-01

A patient with lymphadenopathic toxoplasmosis characterized by prolonged symptoms and repeated relapses with isolation of toxoplasma from lymph nodes is described. As the disease persisted and progressed, striking immunologic changes occurred that ultimately resulted in a state of extreme hyperglobulinemia associated with impaired delayed hypersensitivity responses. The case in question illustrates that progressive infection may occur in the face of high antibody levels of all immunoglobulin types whereas the only demonstrable immunologic impairment was of delayed hypersensitivity.

An outer membrane protein (porin) as an eliciting antigen for delayed-type hypersensitivity in murine salmonellosis.

PubMed Central

Udhayakumar, V; Muthukkaruppan, V R

1987-01-01

The porin, an outer membrane protein of Salmonella typhimurium, was found to be a suitable antigen for eliciting delayed-type hypersensitivity in mouse salmonellosis. Histological examination of the reaction site revealed that the porin was superior to other antigenic preparations in eliciting a typical delayed-type hypersensitivity reaction consisting of mononuclear cell infiltration without polymorphonuclear cell contamination. This study indicates the importance of using a suitable protein antigen from S. typhi for human application. Images PMID:3028963

An adult case of chronic active Epstein-Barr virus infection with interstitial pneumonitis.

PubMed

Joo, Eun-Jeong; Ha, Young Eun; Jung, Dong Sik; Cheong, Hae Suk; Wi, Yu Mi; Song, Jae-Hoon; Peck, Kyong Ran

2011-12-01

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment.

Methotrexate-induced pneumonitis in Crohn's disease. Case report and review of the literature

PubMed Central

2010-01-01

Methotrexate (MTX) is a folate-antagonist used in several neoplastic and inflammatory diseases. Reports of pulmonary complications in patients given low-dose MTX therapy are increasing. Pulmonary toxicity from MTX has a variable frequency and can present with different forms. Most often MTX-induced pneumonia in patients affected by rheumatoid arthritis (RA) is reported. In this paper we describe a case of MTX-related pneumonitis in a relatively young woman affected by Crohn's disease who presented non-productive cough, fever and dyspnea on exercise. Chest X-ray demonstrated bilateral interstitial infiltrates and at computed tomography (CT) ground-glass opacities appeared in both lungs. At spirometry an obstructive defect was demonstrated. A rapid improvement of symptoms and the regression of radiographic and spirometric alterations was achieved through MTX withdrawal and the introduction of corticosteroid therapy. PMID:22958737

Efficacy of desensitizing products containing 8% arginine and calcium carbonate for hypersensitivity relief in MIH-affected molars: an 8-week clinical study.

PubMed

Bekes, Katrin; Heinzelmann, Karolin; Lettner, Stefan; Schaller, Hans-Günter

2017-09-01

The objective of this study was to compare the efficacy in reducing hypersensitivity in molar incisor hypomineralization (MIH)-affected molars immediately and over 8 weeks combining a single in-office application and a homed-based program with desensitizing products containing 8% arginine and calcium carbonate. Nineteen children with at least one MIH-affected molar with hypersensitivity were included. Hypersensitivity was assessed with an evaporative (air) stimulus and a tactile stimulus. Each child received a single in-office treatment with a desensitizing paste containing 8% arginine and calcium carbonate (elmex Sensitive Professional desensitizing paste), followed by 8 weeks of brushing twice daily with a desensitizing toothpaste containing 8% arginine, calcium carbonate with 1450 ppm fluoride (elmex Sensitive Professional toothpaste), using the elmex Sensitive Professional toothbrush. Additionally, the corresponding mouthwash (elmex Sensitive Professional mouthwash) was used. Clinical assessments were made at baseline, immediately after the in-office treatment and after 1, 2, 4 and 8 weeks of brushing twice daily. Fifty-six molars with an air blast hypersensitivity score of 2 or 3 (Schiff Cold Air Sensitivity Scale) were included. Application of the desensitizing paste decreased hypersensitivity significantly immediately and throughout the 8 weeks recalls (p < 0.001). In conclusion, 8% arginine and calcium carbonate were able to reduce hypersensitivity successfully during this 8-week trial. Hypersensitivity is a major complaint in patients with MIH. This is the first study evaluating the desensitizing effect of a desensitizing paste containing 8% arginine and calcium carbonate in patients with MIH.

Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity

PubMed Central

Audicana, M. Teresa; Kennedy, Malcolm W.

2008-01-01

Summary: 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. PMID:18400801

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dobrocky, Tomas, E-mail: tomas.dobrocky@insel.ch; Fuerstner, Markus, E-mail: markus.fuerstner@insel.ch; Klaeser, Bernd, E-mail: bernd.klaeser@insel.ch

2015-08-15

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

Skin testing for immediate hypersensitivity to corticosteroids: a case series and literature review.

PubMed

Baker, A; Empson, M; The, R; Fitzharris, P

2015-03-01

Immediate hypersensitivity to corticosteroids is reported to occur with an incidence of 0.1%. The largest previous case series reporting corticosteroid skin testing has seven patients. We identified 23 patients (mean age 50 years, 65% female) from Auckland City Hospital who underwent skin testing (ST) for suspected corticosteroid hypersensitivity between July 2005 and April 2012. We performed a retrospective clinical case note review detailing clinical history of reaction, skin test results and subsequent management. Most patients (21/23) had a standard panel of testing with prednisolone, triamcinolone, methylprednisolone, hydrocortisone and dexamethasone. Skin tests used a 10% steroid stock concentration for skin prick tests (SPT) and dilutions of 1 : 1000, 1 : 100 and 1 : 10 for subsequent intradermal testing. A weal 3 mm greater than the negative control was considered positive. A total of 23 patients were identified who had skin testing for suspected acute hypersensitivity to corticosteroids, eight of which had a history of anaphylaxis. From 28 reactions (in 23 patients), the most common route of administration was intra-articular (13), followed by oral (7), intravenous (3) and other (5). Skin tests were positive in 8/23 patients, and 7/8 of these patients had a history of corticosteroid-associated anaphylaxis. Skin tests were positive at either the skin prick test or intradermal stages. There was evidence suggesting clinical and skin test cross-reactivity between corticosteroids in one patient. One patient had a positive skin test, but negative oral challenge suggesting the skin test was false positive. Skin tests were negative in 15/23 patients. One patient had a negative prednisolone skin test and positive unblinded oral challenge, suggesting a false-negative skin test. Skin testing can provide sufficient evidence to diagnose allergy in patients with a clear history of immediate hypersensitivity to corticosteroids such as anaphylaxis. Both skin prick

Kodak film type SO-394-4-1 mottling and hypersensitization test

NASA Technical Reports Server (NTRS)

Weinstein, M. S.

1972-01-01

A number of tests were conducted to show the effects of various environmental conditions in terms of mottling and hypersensitization on Kodak Film type SO-394-4-1. The first two weeks of environmental testing is described, along with the test plan and matrix.

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

PubMed

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

2017-03-01

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

Analysis of the Protective Biochemical and Pathologic Effects of Aminoguanidine on an Experimental Aspiration Pneumonitis Model Induced by Bile Acids

PubMed Central

Karli, Rifat; Alacam, Hasan; Duran, Latif; Alici, Omer; Kati, Celal; Karli, Arzu; Guzel, Ahmet

2012-01-01

Background Gastroesophageal reflux (GER) is a common clinical pathology detected in childhood. Bile acids (BAs) are present in reflux and cause various pathologies in the esophagus, the larynx, and the lungs. Objective We aimed to show if aminoguanidine (AG) contributes to the biochemical and histopathologic treatment of experimental aspiration pneumonitis induced by BAs. Methods Twenty-eight female Sprague Dawley rats were used. There were 4 groups in the study: (1) group aspirated with 0.9% saline (n = 7), (2) group aspirated with 0.9% saline and treated with AG (n = 7), (3) group aspirated with a solution of 10 mg/kg taurocholic acid and 5 mg/kg taurochenodeoxycholate (n = 7), and (4) group aspirated with BA and treated with AG (n = 7). The saline and BA solutions were administered as 1 mL/kg intratracheally. The AG was administered intraperitoneally twice a day at a 150 mg/kg dose for 7 days. The different histopathologic and biochemical parameters were analyzed. Results Clara cell protein 16 and malondialdehyde levels were found to be significantly higher in the BA group than in the group where saline was administered; however, they were significantly lower in the BA + AG group than in the BA group. The total superoxide dismutase activity decreased significantly in the BA group compared with the group where saline was administered. A significant increase in superoxide dismutase activity was observed in the BA + AG group when compared with the group where only BA was administered. When the group where BA was administered solely was compared with the group where saline was administered, peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar histiocytes, interstitial fibrosis, and granuloma were significantly higher in the BA group than in the saline group. When the BA + AG group was compared with the BA group, peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar histiocytes, interstitial fibrosis, and

Evaluation of T-cell activation in the duodenum of dogs with cutaneous food hypersensitivity.

PubMed

Veenhof, Eveline Z; Rutten, Victor P; van Noort, Ronald; Knol, Edward F; Willemse, Ton

2010-04-01

To determine whether skin-related clinical signs in cutaneous food hypersensitivity (CFH) coincide with immune reactivity in the intestine in dogs. 11 dogs with CFH without intestinal clinical signs and 8 healthy control dogs. After a provocation and elimination diet, the duodenal gene expression levels of Th1-, Th2- and Treg-related cytokines and transcription factors were investigated by means of quantitative PCR assay. The presence of CD3(+), CD8(+), CD4(+), CD1c(+), gammadelta T-cell receptor(+), and major histocompatibility complex II(+) cells in duodenal epithelium and lamina propria were determined. The expression of Th1-, Th2-, and Treg-related genes in dogs with CFH and healthy control dogs was similar. Although clinical signs disappeared, there was no effect of the elimination diet on cytokines, transcription factors, or cellular phenotypes. No change in T-cell phenotypes or a distinct Th1, Th2, or Treg profile was detected in the duodenum of dogs with only cutaneous clinical signs of food hypersensitivity. This suggested that the intestinal mucosa is not the primary site of T-cell activation that eventually leads to cutaneous food hypersensitivity.

Diagnosis of carotid sinus hypersensitivity in older adults: carotid sinus massage in the upright position is essential

PubMed Central

Parry, S; Richardson, D; O'Shea, D; Sen, B; Kenny, R

2000-01-01

OBJECTIVE—To assess the diagnostic value of supine and upright carotid sinus massage in elderly patients.
DESIGN—Prospective controlled cohort study.
SETTING—Three inner city accident and emergency departments and a dedicated syncope facility.
PATIENTS—1375 consecutive patients aged > 55 years presenting with unexplained syncope and drop attacks; 25 healthy controls.
INTERVENTIONS—Bilateral supine carotid sinus massage, repeated in the 70° head up tilt position if the initial supine test was not diagnostic of cardioinhibitory and mixed carotid sinus hypersensitivity.
MAIN OUTCOME MEASURES—Diagnosis of cardioinhibitory or mixed carotid sinus hypersensitivity; clinical characteristics of supine v upright positive groups.
RESULTS—226 patients were excluded for contraindications to carotid sinus massage. Of 1149 patients undergoing massage, 223 (19%) had cardioinhibitory or mixed carotid sinus hypersensitivity; 70 (31%) of these had a positive response to massage with head up tilt following negative supine massage (95% confidence interval, 25.3% to 37.5%). None of the healthy controls showed carotid sinus hypersensitivity on erect or supine massage. The initially positive supine test had 74% specificity and 100% sensitivity; these were both 100% for the upright positive test. The clinical characteristics of the supine v upright positive subgroups were similar.
CONCLUSIONS—The diagnosis of carotid sinus hypersensitivity amenable to treatment by pacing may be missed in one third of cases if only supine massage is performed. Massage should be done routinely in the head up tilt position if the initial supine test is negative.


Keywords: carotid sinus; tilt table testing; syncope; elderly patients PMID:10618329

Effectiveness of an in-office arginine-calcium carbonate paste on dentine hypersensitivity in periodontitis patients: a double-blind, randomized controlled trial.

PubMed

Pepelassi, Eudoxie; Rahiotis, Christos; Peponi, Eleni; Kakaboura, Afrodite; Vrotsos, Ioannis

2015-01-01

The aim of this single-centre, two-cell, double-blind, randomized controlled clinical study was to evaluate the effectiveness of an in-office desensitizing paste containing 8% arginine and calcium carbonate in providing relief on dentine hypersensitivity immediately after scaling and root planing and its sustained relief over a 6-week period. Fifty periodontitis subjects presenting hypersensitivity were subjected to scaling and root planing and in-office application of either 8% arginine and calcium carbonate desensitizing paste (25 subjects, test group) or fluoride-free prophylaxis paste (25 subjects, control group). Air-blast hypersensitivity was assessed using Schiff and Visual Analogue (VAS) scales at baseline, post-scaling, post-application, 2, 4 and 6 weeks. At all evaluation times, the test group presented significant % reduction in hypersensitivity relative to post-scaling (t-test, p < 0.05) (Schiff - Test: 57, 58.6, 60.2, 68; 28.6, 22.2, 23, 23) (VAS - Test: 60, 55.6, 60.1, 68.4; 25.9, 18.2, 20.6, 22.7) and significant % hypersensitivity difference relative to control (ancova, p < 0.05) (Schiff: 38.9, 45.9, 47.4, 57.7; VAS: 49.1, 48.9, 52.6, 61). The single in-office application of the 8% arginine-calcium carbonate desensitizing paste after scaling and root planing provided significant immediate reduction in dentine hypersensitivity, which sustained over a 6-week period. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Examining a Dual-Process Model of Desensitization and Hypersensitization to Community Violence in African American Male Adolescents.

PubMed

Gaylord-Harden, Noni K; Bai, Grace J; Simic, Dusan

2017-10-01

The purpose of the current study was to examine a dual-process model of reactivity to community violence exposure in African American male adolescents from urban communities. The model focused on desensitization and hypersensitization effects as well as desensitization and hypersensitization as predictors of aggressive behavior. Participants were 133 African American male high school students, mean age = 15.17 years, SD = 0.96. Participants completed measures of exposure to community violence, depressive symptoms, hyperarousal symptoms, aggressive beliefs, and aggressive behaviors at two time points. Community violence exposure predicted changes in aggression, β = .25, p = .004, and physiological arousal, β = .22, p = .010, over time, but not aggressive beliefs. The curvilinear association between community violence exposure and changes in depression over time was not significant, β = .42, p = .083, but there was a significant linear association between the exposure to community violence (ECV) and changes in levels of depression over time, β = .21, p = .014. Results indicated a significant mediation effect for hyperarousal on the association between community violence exposure and aggressive behavior, B = 0.20, 95% CI = [0.04, 0.54]. Results showed support for physiological hypersensitization, with hypersensitization increasing the risk for aggressive behavior. Copyright © 2017 International Society for Traumatic Stress Studies.

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.

Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches

PubMed Central

de las Vecillas Sánchez, Leticia; Alenazy, Leila A.; Garcia-Neuer, Marlene; Castells, Mariana C.

2017-01-01

Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS). DS induces a temporary hyporesponsive state by incremental escalation of sub-optimal doses of the offending drug. In vitro models have shown evidence that IgE desensitization is an antigen-specific process which blocks calcium flux, impacts antigen/IgE/FcεRI complex internalization and prevents the acute and late phase reactions as well as mast cell mediator release. Through a “bench to bedside” approach, in vitro desensitization models help elucidate the molecular pathways involved in DS, providing new insights to improved desensitization protocols for all patients. The aim of this review is to summarize up to date information on the drug HSRs, the IgE mediated mechanisms of desensitization, and their clinical applications. PMID:28632196

Essential Role of Lymph Nodes in Contact Hypersensitivity Revealed in Lymphotoxin-α–Deficient Mice

PubMed Central

Rennert, Paul D.; Hochman, Paula S.; Flavell, Richard A.; Chaplin, David D.; Jayaraman, Sundararajan; Browning, Jeffrey L.; Fu, Yang-Xin

2001-01-01

Lymph nodes (LNs) are important sentinal organs, populated by circulating lymphocytes and antigen-bearing cells exiting the tissue beds. Although cellular and humoral immune responses are induced in LNs by antigenic challenge, it is not known if LNs are essential for acquired immunity. We examined immune responses in mice that lack LNs due to genetic deletion of lymphotoxin ligands or in utero blockade of membrane lymphotoxin. We report that LNs are absolutely required for generating contact hypersensitivity, a T cell–dependent cellular immune response induced by epicutaneous hapten. We show that the homing of epidermal Langerhans cells in response to hapten application is specifically directed to LNs, providing a cellular basis for this unique LN function. In contrast, the spleen cannot mediate contact hypersensitivity because antigen-bearing epidermal Langerhans cells do not access splenic white pulp. Finally, we formally demonstrate that LNs provide a unique environment essential for generating this acquired immune response by reversing the LN defect in lymphotoxin-α−/− mice, thereby restoring the capacity for contact hypersensitivity. PMID:11390430

Type IV Hypersensitivity to Gold Weight Upper-Eyelid Implant: Case Report and Review of the Literature.

PubMed

Kilduff, Caroline L S; Casswell, Edward J; Imonikhe, Richard; Marjanovic, Branka

2017-05-04

Complications associated with gold-weight insertion for lagophthalmos are uncommon, recent reports have provided evidence to suggest that type IV hypersensitivity to gold can cause a persistent inflammatory reaction. We present a case of a 46-year-old man who experienced persistent post-operative inflammation, and summarize previously documented cases. This patient underwent uncomplicated insertion of an upper eyelid gold weight for right-sided facial nerve palsy. He had no allergies or implanted metalwork. Post-operatively erythema was noted at seven-weeks and did not resolve. The weight was removed after six-months. The histopathological findings were in keeping with type IV hypersensitivity and similar to previous cases. Although infrequent, this complication has poor outcomes. The definitive management is removal of the weight. Information regarding implanted gold, and previous reactions should be elicited pre-operatively. Type IV hypersensitivity should be considered in patients with persistent inflammation that do not respond to antibiotic or steroid therapy.

Occupational therapy students' perceptions of occupational therapy.

PubMed

Turpin, Merrill June; Rodger, Sylvia; Hall, Anna R

2012-10-01

An understanding of students' perceptions of occupational therapy on entry is required to recognise how professional socialisation occurs through curriculum. Findings pertain to a qualitative study investigating students' perceptions of occupational therapy upon entry to two occupational therapy programmes in Australia. Students commencing Bachelor of Occupational Therapy and Masters of Occupational Therapy Studies programmes participated in the study (n = 462). A purpose-designed questionnaire was distributed to students in the first lecture of each programme. Preliminary analysis comprised identification of keywords/phrases and coding categories were generated from patterns of keywords. Frequency counts and percentages of keywords/phrases within categories were completed. Students' responses were categorised as 'what' occupational therapists do; 'how' they do it; 'why' they do it; and 'who' they work with. In 'what' occupational therapists do students frequently described 'helping' people. Both undergraduate and graduate entry masters students used the term 'rehabilitation' to describe how occupational therapy is done, with graduate entry students occasionally responding with 'through occupation' and 'modifying the environment'. Students perceived the 'why' of occupational therapy as getting back to 'everyday activities', with some students emphasising returning to 'normal' activities or life. Regarding the 'who' category, students also thought occupational therapists worked with people with an 'injury' or 'disability'. Students entered their occupational therapy programmes with perceptions consistent with the general public's views of occupational therapy. However, graduate entry students exposed to a pre-reading package prior to entry had more advanced occupational therapy concepts than undergraduate students. © 2011 The Authors. Australian Occupational Therapy Journal © 2011 Occupational Therapy Australia.

Management of stinging insect hypersensitivity: a 5-year retrospective medical record review.

PubMed

Johnson, Thomas; Dietrich, Jeffrey; Hagan, Larry

2006-08-01

The Joint Task Force on Practice Parameters for Allergy and Immunology recommends that patients with a history of a systemic reaction to an insect sting be educated on ways to avoid insect stings, carry injectable epinephrine for emergency self-treatment, undergo specific IgE testing for stinging insect sensitivity, and be considered for immunotherapy. To review frontline providers' documented care and recommendations for imported fire ant and flying insect hypersensitivity reactions. A retrospective medical record review was performed of emergency department and primary care clinic visits between November 1, 1999, and November 30, 2004. Using International Classification of Diseases, Ninth Revision, codes, medical records were selected for review to identify patients with potential insect hypersensitivity. A total of 769 medical records from patients who experienced an insect sting were reviewed. Of 120 patients with a systemic reaction, 66 (55.0%) received a prescription for injectable epinephrine, and 14 (11.7%) were given information regarding avoidance of the offending insect. Forty-seven patients with systemic reactions (39.2%) were referred to an allergist. Of 28 patients who kept their appointments and underwent skin testing, 3 had negative results and 25 (89%) had positive results and were advised to start immunotherapy. Adherence to the stinging insect hypersensitivity practice parameter recommendations is poor. Many patients who have experienced a systemic reaction after an insect sting and have sought medical care are not afforded an opportunity for potentially lifesaving therapy.

Hypersensitivity reaction to ranitidine: description of a case and review of the literature.

PubMed

Foti, Caterina; Cassano, Nicoletta; Panebianco, Rosanna; Calogiuri, Gian Franco; Vena, Gino A

2009-01-01

Ranitidine is an H2-receptor antagonist which is usually well tolerated. Hypersensitivity reactions to ranitidine, as well as other H2 antihistamines, have been rarely described. We report the case of a 47-year-old woman who developed an anaphylactic reaction to ranitidine used as intravenous premedication before anesthesia induction. The patient's history revealed that previous use of oral ranitidine for a peptic ulcer disease did not cause any adverse reaction. Intradermal test with ranitidine at a dilution of 1:100 gave an intense positive reaction. The protective role of H2-receptor antagonists as premedication is still unclear and should be carefully reconsidered on the basis of the available controversial evidence and the possible risk of hypersensitivity reactions.

Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats

PubMed Central

Diesel, Alison

2017-01-01

Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly “feline atopic syndrome” when compared to dogs or people. This article aims to review what is currently known in regards to allergic skin disease in the feline patient, with focus on non-flea, non-food hypersensitivity dermatitis. PMID:29056684

Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats.

PubMed

Diesel, Alison

2017-05-09

Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly "feline atopic syndrome" when compared to dogs or people. This article aims to review what is currently known in regards to allergic skin disease in the feline patient, with focus on non-flea, non-food hypersensitivity dermatitis.

21 CFR 310.103 - New drug substances intended for hypersensitivity testing.

Code of Federal Regulations, 2014 CFR

2014-04-01

... testing. 310.103 Section 310.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 310.103 New drug substances intended for hypersensitivity testing. (a) The Food and Drug... testing is not promoted by the manufacturer or distributor. (2) The new drug substance requested is an...

21 CFR 310.103 - New drug substances intended for hypersensitivity testing.

Code of Federal Regulations, 2012 CFR

2012-04-01

... testing. 310.103 Section 310.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 310.103 New drug substances intended for hypersensitivity testing. (a) The Food and Drug... testing is not promoted by the manufacturer or distributor. (2) The new drug substance requested is an...

21 CFR 310.103 - New drug substances intended for hypersensitivity testing.

Code of Federal Regulations, 2011 CFR

2011-04-01

... testing. 310.103 Section 310.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 310.103 New drug substances intended for hypersensitivity testing. (a) The Food and Drug... testing is not promoted by the manufacturer or distributor. (2) The new drug substance requested is an...

21 CFR 310.103 - New drug substances intended for hypersensitivity testing.

Code of Federal Regulations, 2013 CFR

2013-04-01

... testing. 310.103 Section 310.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 310.103 New drug substances intended for hypersensitivity testing. (a) The Food and Drug... testing is not promoted by the manufacturer or distributor. (2) The new drug substance requested is an...

21 CFR 310.103 - New drug substances intended for hypersensitivity testing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... testing. 310.103 Section 310.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 310.103 New drug substances intended for hypersensitivity testing. (a) The Food and Drug... testing is not promoted by the manufacturer or distributor. (2) The new drug substance requested is an...

An Adult Case of Chronic Active Epstein-Barr Virus Infection with Interstitial Pneumonitis

PubMed Central

Joo, Eun-Jeong; Ha, Young Eun; Jung, Dong Sik; Cheong, Hae Suk; Wi, Yu Mi; Song, Jae-Hoon

2011-01-01

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment. PMID:22205850

Minocycline Prevents Muscular Pain Hypersensitivity and Cutaneous Allodynia Produced by Repeated Intramuscular Injections of Hypertonic Saline in Healthy Human Participants.