The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.
If you have any questions or comments, please contact us.
OBJECTIVE - To assess drug reactions (ADRs) encountered by practicing urologists for contrast instilled into the urinary collecting system, and to describe current practice patterns regarding contrast administration into the urinary tract for patients with known contrast allergies.
METHODS - Endourological Society members were e-mailed a web-based survey about their prior experience with contrast-related ADRs and practices for contrast administration into the urinary tract among patients with known intravenous contrast allergies. Chi-squared analysis was used to compare management patterns between patients with established allergies and those without.
RESULTS - An estimated 2300-2500 e-mails were reached, resulting in an estimated response rate of 6.3%-8%. Over 75% of respondents were fellowship trained. Average time in practice was 16 years, and respondents performed a mean of 6.7 urologic contrast studies per week. Among respondents, 32.6%, 14.7%, and 4.0% had treated at least 1 patient with a mild, moderate, or severe reaction, respectively. Contrast-related ADRs were most commonly associated with retrograde pyelogram (50%). For patients with known contrast allergies, 5.4% pursue additional work-up before administering contrast in the urinary tract. Pretreatment with antihistamine or steroids is used by 24.8% and 23.4%, respectively. When performing retrograde pyelograms for such patients, urologists are more likely to use dilute contrast (P = .003), but otherwise do not significantly alter technique.
CONCLUSION - Contrast ADRs are encountered not infrequently among practicing urologists. There is notable practice variation in the management of patients with known contrast allergies, though the overall perceived risk of contrast use in these patients is low, provided good technique is used.
Copyright © 2018 Elsevier Inc. All rights reserved.
BACKGROUND - Food allergy is an increasingly common health problem in Western populations. Epidemiological studies have suggested both positive and negative associations between food allergy and infection with the gastric bacterium Helicobacter pylori.
OBJECTIVE - The objective of this work was to investigate whether experimental infection with H. pylori, or prophylactic treatment with H. pylori-derived immunomodulatory molecules, affects the onset and severity of food allergy, either positively or negatively.
METHODS - We infected neonatal C57BL/6 or C3H mice with H. pylori or treated animals with H. pylori components (bacterial lysate or the immunomodulator VacA) and subsequently subjected them to four different protocols for food allergy induction, using either ovalbumin or peanut extract as allergens for sensitization and challenge. Readouts included anaphylaxis scoring, quantification of allergen-specific serum IgE and IgG1 and of the mast cell protease MCPT1, as well as splenic T-helper-2 cell-derived cytokine production. Mesenteric lymph node CD4 FoxP3 regulatory T cells were subjected to flow cytometric quantification and sorting followed by qRT-PCR, and to DNA methylation analyses of the Treg-specific demethylated region (TSDR) within the FOXP3 locus.
RESULTS - Mice that had been infected with H. pylori or treated with H. pylori-derived immunomodulators showed reduced anaphylaxis upon allergen sensitization and challenge, irrespective of the allergen used. Most of the immunologic assays confirmed a protective effect of H. pylori. CD4 FoxP3 T cells were more abundant in protected mice and exhibited a stable Treg phenotype characterized by FOXP3 TSDR demethylation.
CONCLUSIONS AND CLINICAL RELEVANCE - Helicobacter pylori confers protection against the anaphylaxis associated with ovalbumin and peanut allergy and affects the epigenome of T cells, thereby promoting stable Treg differentiation and functionality. Prophylactic treatment with H. pylori-derived immunomodulators appears to be a promising strategy for food allergy prevention.
© 2017 John Wiley & Sons Ltd.
Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system, and their occurrence is not predictable based on the known pharmacological action of the drug's therapeutic effect. Off-target ADRs may or may not be associated with immunological memory, although they can manifest with a variety of shared clinical features, including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus and bronchospasm. Discovery of specific genes associated with a particular ADR phenotype is a foundational component of clinical translation into screening programmes for their prevention. In this review, genetic associations of off-target drug-induced ADRs that have a clinical phenotype suggestive of an immunologically mediated process and their mechanisms are highlighted. A significant proportion of these reactions lack immunological memory and current data are informative for these ADRs with regard to disease pathophysiology, therapeutic targets and biomarkers which may identify patients at greatest risk. Although many serious delayed immune-mediated (IM)-ADRs show strong human leukocyte antigen associations, only a small subset have successfully been implemented in screening programmes. More recently, other factors, such as drug metabolism, have been shown to contribute to the risk of the IM-ADR. In the future, pharmacogenomic targets and an understanding of how they interact with drugs to cause ADRs will be applied to drug design and preclinical testing, and this will allow selection of optimal therapy to improve patient safety.
© 2017 The British Pharmacological Society.
Allergic airway diseases are immune disorders associated with heightened type 2 immune responses and IL-5 and IL-13 production at the site of inflammation. We have previously reported that cyclooxygenase (COX) inhibition by indomethacin augmented allergic airway inflammation in a STAT6-independent manner. However, the key COX product(s) responsible for restraining indomethacin-mediated STAT6-independent allergic inflammation is unknown. In this study, using the mouse model of OVA-induced allergic airway inflammation, we identified that PGI2 receptor (IP) signaling was critical for indomethacin-induced, STAT6-independent proallergic effects. We demonstrated that IP deficiency increased inflammatory cell infiltration, eosinophilia, and IL-5 and IL-13 expression in the lung in a STAT6-independent manner. The augmented STAT6-independent allergic inflammation correlated with enhanced primary immune responses to allergic sensitization and elevated production of multiple inflammatory chemokines (CCL11, CCL17, CCL22, and CXCL12) in the lung after allergen challenge. We also showed that the PGI2 analogue cicaprost inhibited CD4 T cell proliferation and IL-5 and IL-13 expression in vitro, and IP deficiency diminished the stimulatory effect of indomethacin on STAT6-independent IL-5 and IL-13 responses in vivo. The inhibitory effects of PGI2 and the IP signaling pathway on CD4 T cell activation, inflammatory chemokine production, and allergic sensitization and airway inflammation suggest that PGI2 and its analogue iloprost, both Food and Drug Administration-approved drugs, may be useful in treating allergic diseases and asthma. In addition, inhibiting PGI2 signaling by drugs that either block PGI2 production or restrain IP signaling may augment STAT6-independent pathways of allergic inflammation.
Copyright © 2016 by The American Association of Immunologists, Inc.
OBJECTIVE - Peanut allergy (PA) clearly has a heritable component. Specific genetic contributions are unknown, but human leukocyte antigen (HLA) loci are obvious candidates. This review focuses on emerging studies of HLA associations with PA.
DATA SOURCES - PubMed was searched with no time limitations using key terms human leukocyte antigen, HLA, MHC, peanut, peanut hypersensitivity, and peanut allergy.
STUDY SELECTIONS - Qualifying studies were English-language reports of genetic analyses examining PA and HLA associations.
RESULTS - Seven relevant citations were identified, which were published from 1996 to 2015. Early studies using candidate gene approaches found associations between PA and HLA-DR and -DQ alleles (HLA-DRB1*08 and DQB1*06:03P) when comparing subjects with peanut allergy with nonallergic unrelated control groups. No significant associations were found between siblings with and without peanut allergy. However, a recent large genomewide association study of patients with peanut allergy and their family members found 2 PA-associated single-nucleotide polymorphisms (rs9275596 and rs7192) mapping to regions involving the HLA-DR and HLA-DQ genes. Associations with differential DNA methylation partly mediated the associations between PA and single-nucleotide polymorphisms.
CONCLUSION - Early studies using candidate gene approaches identified HLA associations with PA compared with the general population, suggesting a link with atopy but failing to identify a PA-specific association. These studies had various limitations that included small samples. The most compelling evidence for a PA-specific HLA association comes from a genomewide association study, which examined the entire genome in large, well-defined, related cohorts. More research is needed to validate and replicate these findings, to perform fine genetic mapping of specific HLA loci, and to demonstrate underlying mechanisms of HLA contributions to PA.
Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Prostaglandins (PGs) are products of the COX pathway of arachidonic acid metabolism. There are five primary PGs, PGD₂, PGE₂, PGF₂, PGI₂ and thromboxane A₂, all of which signal through distinct seven transmembrane, G-protein coupled receptors. Some PGs may counteract the actions of others, or even the same PG may have opposing physiologic or immunologic effects, depending on the specific receptor through which it signals. In this review, we examine the effects of COX activity and the various PGs on allergic airway inflammation and physiology that is associated with asthma. We also highlight the potential therapeutic benefit of targeting PGs in allergic lung inflammation and asthma based on basic science, animal model and human studies.
Antimicrobial efficacy and toxicity varies between individuals owing to multiple factors. Genetic variants that affect drug-metabolizing enzymes may influence antimicrobial pharmacokinetics and pharmacodynamics, thereby determining efficacy and/or toxicity. In addition, many severe immune-mediated reactions have been associated with HLA class I and class II genes. In the last two decades, understanding of pharmacogenomic factors that influence antimicrobial efficacy and toxicity has rapidly evolved, leading to translational success such as the routine use of HLA-B*57:01 screening to prevent abacavir hypersensitivity reactions. This article examines recent advances in the field of antimicrobial pharmacogenomics that potentially affect treatment efficacy and toxicity, and challenges that exist between pharmacogenomic discovery and translation into clinical use.
Amphibians are suffering unprecedented global declines. A leading cause is the infectious disease chytridiomycosis caused by the chytrid fungus Batrachochytrium dendrobatidis. Chytridiomycosis is a skin disease which disrupts transport of essential ions leading to death. Soluble factors produced by B. dendrobatidis impair amphibian and mammalian lymphocytes in vitro, but previous studies have not shown the effects of these inhibitory factors in vivo. To demonstrate in vivo inhibition of immunity by B. dendrobatidis, a modified delayed-type-hypersensitivity (DTH) protocol was developed to induce innate and adaptive inflammatory swelling in the feet of Xenopus laevis by injection of killed bacteria or phytohemagglutinin (PHA). Compared to previous protocols for PHA injection in amphibians, this method induced up to 20-fold greater inflammatory swelling. Using this new protocol, we measured DTH responses induced by killed bacteria or PHA in the presence of B. dendrobatidis supernatants. Swelling induced by single injection of PHA or killed bacteria was not significantly affected by B. dendrobatidis supernatants. However, swelling caused by a secondary injection of PHA, was significantly reduced by B. dendrobatidis supernatants. As previously described in vitro, factors from B. dendrobatidis appear to inhibit lymphocyte-mediated inflammatory swelling but not swelling caused by an inducer of innate leukocytes. This suggests that B. dendrobatidis is capable of inhibiting lymphocytes in a localized response to prevent adaptive immune responses in the skin. The modified protocol used to induce inflammatory swelling in the present study may be more effective than previous methods to investigate amphibian immune competence, particularly in nonmodel species.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
While a doctor-diagnosis of asthma is associated with an increased risk of pain and acute chest syndrome (ACS) in children with sickle cell anemia (SCA), little is known about the relationship between specific asthma characteristics and clinical factors and future morbidity in children with SCA. We evaluated the relationship between (i) asthma risk factors at the time of a clinical visit (respiratory symptoms, maternal history of asthma, allergy skin tests, spirometry results) and (ii) the known risk factor of ACS early in life, on prospective pain and ACS episodes in a cohort of 159 children with SCA followed from birth to a median of 14.7 years. An ACS episode prior to 4 years of age, (incidence rate ratio [IRR] = 2.84; P < 0.001], female gender (IRR = 1.80; P = 0.009), and wheezing causing shortness of breath (IRR = 1.68; P = 0.042) were associated with future ACS rates. We subsequently added spirometry results (obstruction defined as FEV1 /FVC less than the lower limits of normal; and bronchodilator response, FEV1 ≥ 12%) and prick skin test responses to the model. Only ≥ 2 positive skin tests had a significant effect (IRR 1.87; P = 0.01). Thus, early in life ACS events, wheezing causing shortness of breath, and ≥ 2 positive skin tests predict future ACS events.
© 2014 Wiley Periodicals, Inc.
BACKGROUND - The prevalence of allergic diseases has doubled in developed countries in the past several decades. Cyclooxygenase (COX)-inhibiting drugs augmented allergic diseases in mice by increasing allergic sensitization and memory immune responses. However, whether COX inhibition can promote allergic airway diseases by inhibiting immune tolerance is not known.
OBJECTIVE - To determine the role of the COX pathway and prostaglandin I2 (PGI2) signaling through the PGI2 receptor (IP) in aeroallergen-induced immune tolerance.
METHODS - Wild-type (WT) BALB/c mice and IP knockout mice were aerosolized with ovalbumin (OVA) to induce immune tolerance prior to immune sensitization with an intraperitoneal injection of OVA/alum. The COX inhibitor indomethacin or vehicle was administered in drinking water to inhibit enzyme activity during the sensitization phase. Two weeks after sensitization, the mice were challenged with OVA aerosols. Mouse bronchoalveolar lavage fluid was harvested for cell counts and TH2 cytokine measurements.
RESULTS - WT mice treated with indomethacin had greater numbers of total cells, eosinophils, and lymphocytes, and increased IL-5 and IL-13 protein expression in BAL fluid compared to vehicle-treated mice. Similarly, IP knockout mice had augmented inflammation and TH2 cytokine responses compared to WT mice. In contrast, the PGI2 analog cicaprost attenuated the anti-tolerance effect of COX inhibition.
CONCLUSION - COX inhibition abrogated immune tolerance by suppressing PGI2 IP signaling, suggesting that PGI2 signaling promotes immune tolerance and that clinical use of COX-inhibiting drugs may increase the risk of developing allergic diseases.
Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.