Pathogenesis of chronic urticaria Kaplan, A. P.; Greaves, M.
Clinical and experimental allergy,
June 2009, Letnik:
39, Številka:
6
Journal Article
Recenzirano
Summary
Chronic urticaria is defined as the presence of urticaria (hives) for at least 6 weeks with the assumption that it occurs daily or close to it. If we eliminate physical urticarias and ...urticarial vasculitis from consideration, the remainder can be divided into autoimmune chronic urticaria (45%) and idiopathic chronic urticaria (55%). The autoimmune subgroup is associated with the IgG anti‐IgE receptor α subunit in 35–40% of patients and IgG anti‐IgE in an additional 5–10%. These autoantibodies have been shown to activate blood basophils and cutaneous mast cells in vitro with augmentation of basophil activation by complement and release of C5a, in particular. Binding methods (immunoblot and ELISA) yield positives in many autoimmune diseases as well as occasional normal subjects or patients with other forms of urticaria but most such sera are non‐functional. Activation of basophils or mast cells causing histamine release is quite specific for chronic urticaria and defines the autoimmune subgroup. Although pathogenicity is not formally proven, the antibodies cause wealing upon intradermal injection, and removal of the autoantibody leads to remission. A cellular infiltrate is seen to be characterized by mast cell degranulation and infiltration of CD4+ T lymphocytes, monocytes, neutrophils, eosinophils, and basophils. The intensity of the infiltrate and clinical severity of the disease (including accompanying angio‐oedema) is more severe in the autoimmune subpopulation. This latter group also has a higher evidence of human leucocyte antigen DR alleles associated with autoimmunity and a 25% incidence of antithyroid antibodies with diagnosed hypothyroidism in some. Hypo‐responsiveness of patients' basophils to anti‐IgE and hyperresponsiveness to serum defines another subpopulation (at least 50%) that overlaps the idiopathic and autoimmune subgroups. Hypo‐responsiveness to anti‐IgE has been shown to be associated with elevated levels of cytoplasmic phosphatases that inhibit degranulation. Reversal of the abnormality is seen with disease remission. Further work will be needed to distinguish whether this is a cause or a consequence of persistent urticaria and to further assess the relationship (or lack thereof) of altered responsiveness (decreased or increased) with the presence or absence of activating autoantibodies.
The monoclonal anti‐immunoglobulin E (IgE) antibody, omalizumab, was the first drug approved for use in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) who remain symptomatic despite ...H1‐antihistamine treatment. Omalizumab binds to free IgE, which lowers free IgE levels and causes FcεRI receptors on basophils and mast cells to be downregulated. It has been shown to improve symptoms of CIU/CSU, but its mechanism of action is not currently understood. Potential mechanisms in CIU/CSU include reducing mast cell releasability, reversing basopenia and improving basophil IgE receptor function, reducing activity of IgG autoantibodies against FcεRI and IgE, reducing activity of IgE autoantibodies against an antigen or autoantigen that has yet to be definitively identified, reducing the activity of intrinsically ‘abnormal’ IgE, and decreasing in vitro coagulation abnormalities associated with disease activity. However, none of these theories alone or in combination fully account for the pattern of symptom improvement seen with omalizumab therapy, and therefore, no one mechanism is likely to be the definitive mechanism of action. Additional research is needed to further clarify the involvement of omalizumab in relieving symptoms associated with the complex, multifactorial pathogenesis of CIU/CSU.
Angioedema is defined as localized and self‐limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive ...mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema.
We investigated the biological lability of fluorescent dissolved organic matter (FDOM) from a temperate Piedmont stream. Plug-flow bioreactors, colonized and maintained with natural stream water, ...were used to determine the concentrations of stream-water biodegradable dissolved organic carbon (BDOC) and relative concentrations of FDOM within operationally defined biodegradability classes. Labile molecules with turnover times of hours are metabolized within the stream reach where they originated; semi-labile molecules with turnover times of days travel out of the reach and are transported downstream before being metabolized; and a more recalcitrant class with a longer but undetermined turnover time flows through the river network without being metabolized. Between 26% and 31% of the DOC was biodegradable, with 8.6% labile and the balance semi-labile. Humic-like FDOM was a proxy for more recalcitrant DOM, exhibiting a ± 2% change as a function of increased bioreactor residence time. Humic-like FDOM represents only the more recalcitrant and perhaps the more hydrophobic constituents and not the ecologically important semi-labile humic substances within the BDOC pool. Tyrosine-like and tryptophan-like FDOM constituents included not only labile DOM, but also semi-labile, and more recalcitrant moieties. For example, 13% of the tryptophan-like FDOM was labile, 14% was semi-labile, and 73% was more recalcitrant, while tyrosine-like FDOM was 100% biodegraded and the majority (44–69%) was classified as labile. Collectively our results challenge some previous assessments of FDOM lability classifications and highlight the need to connect fluorescence characteristics of DOM to residence times of different carbon pools that spiral through a river network.
Identifying biological and behavioural causes of diseases has been one of the central concerns of epidemiology for the past half century. This has led to the development of increasingly sophisticated ...conceptual and analytical approaches focused on the isolation of single causes of disease states. However, the growing recognition that (i) factors at multiple levels, including biological, behavioural and group levels may influence health and disease, and (ii) that the interrelation among these factors often includes dynamic feedback and changes over time challenges this dominant epidemiological paradigm. Using obesity as an example, we discuss how the adoption of complex systems dynamic models allows us to take into account the causes of disease at multiple levels, reciprocal relations and interrelation between causes that characterize the causation of obesity. We also discuss some of the key difficulties that the discipline faces in incorporating these methods into non-infectious disease epidemiology. We conclude with a discussion of a potential way forward.
Male lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) is common in men and can have negative effects on quality of life (QoL). It is the hope that this Guideline ...becomes a reference on the effective evidence-based surgical management of LUTS/BPH.
The evidence team searched Ovid MEDLINE, the Cochrane Library, and the Agency for Healthcare Research and Quality (AHRQ) database to identify studies indexed between January 2007 and September 2017. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1 in supplementary unabridged guideline, http://jurology.com/).
This Guideline provides updated, evidence-based recommendations regarding management of LUTS/BPH utilizing surgery and minimally invasive surgical therapies; additional statements are made regarding diagnostic and pre-operative tests. Clinical statements are made in comparison to what is generally accepted as the gold standard (i.e. transurethral resection of the prostate TURP–monopolar and/or bipolar). This guideline is designed to be used in conjunction with the associated treatment algorithm.
The prevalence and the severity of LUTS increases as men age and is an important diagnosis in the healthcare of patients and the welfare of society. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future surgical options continues to expand.
Computed Tomography is an essential diagnostic tool in the management of COVID-19. Considering the large amount of examinations in high case-load scenarios, an automated tool could facilitate and ...save critical time in the diagnosis and risk stratification of the disease.
A novel deep learning derived machine learning (ML) classifier was developed using a simplified programming approach and an open source dataset consisting of 6868 chest CT images from 418 patients which was split into training and validation subsets. The diagnostic performance was then evaluated and compared to experienced radiologists on an independent testing dataset. Diagnostic performance metrics were calculated using Receiver Operating Characteristics (ROC) analysis. Operating points with high positive (>10) and low negative (<0.01) likelihood ratios to stratify the risk of COVID-19 being present were identified and validated.
The model achieved an overall accuracy of 0.956 (AUC) on an independent testing dataset of 90 patients. Both rule-in and rule out thresholds were identified and tested. At the rule-in operating point, sensitivity and specificity were 84.4 % and 93.3 % and did not differ from both radiologists (p > 0.05). At the rule-out threshold, sensitivity (100 %) and specificity (60 %) differed significantly from the radiologists (p < 0.05). Likelihood ratios and a Fagan nomogram provide prevalence independent test performance estimates.
Accurate diagnosis of COVID-19 using a basic deep learning approach is feasible using open-source CT image data. In addition, the machine learning classifier provided validated rule-in and rule-out criteria could be used to stratify the risk of COVID-19 being present.
Abstract Background The aim was to examine the prevalence and consequences of co-occurring insomnia and hypersomnia symptoms in depressed adults drawn from a representative sample of the U.S. ...population. Method Data from 687 National Comorbidity Survey Replication (NCS-R) respondents meeting criteria for a major depressive episode (MDE) in the past year were included. Respondents completed clinical interviews that assessed 12-month DSM-IV disorders, impairment, mental health treatment, and depressive symptom severity. Outcomes were compared between respondents who experienced insomnia symptoms-only ( N =404), hypersomnia symptoms-only ( N =44), both insomnia and hypersomnia symptoms ( N =184) and no sleep problems ( N =55) during an MDE. Results Insomnia and hypersomnia symptoms co-occurred in 27.7% of respondents with past-year MDEs, most frequently in bipolar spectrum disorders and major depressive disorder with dysthymia. Similar to the insomnia-only group, respondents with co-occurring sleep disturbances had more severe depression, and higher rates of past-year impulse control disorders and suicide planning. Similar to the hypersomnia-only group, respondents with co-occurring sleep disturbances had higher rates of past-year drug use disorders and suicide attempts. Compared to the insomnia-only and no sleep problem groups, respondents with both sleep disturbances were more frequently in mental health treatment, seeing a general practitioner, and taking antidepressants. Limitations The NCS-R is cross-sectional and did not evaluate sleep disorder diagnoses. Conclusions Co-occurring insomnia and hypersomnia symptoms were associated with a more severe MDE. Further research is warranted to more fully understand the joint presentation of insomnia and hypersomnia in depression.
•Laser welding with argon shield gas results in a reduced level of austenite in the weld metal.•Higher welding speeds are linked to lower austenite levels and harder, more brittle welds.•The use of ...nitrogen (instead of argon) as the weld shield gas increases the austenite content of the weld. This is probably linked to the uptake of nitrogen by the weld pool and this compensates to some extent for nitrogen lost by the weld pool as a result of the laser welding process.•Nitrogen as a shield gas has minimal effects on weld hardness but improves weld toughness.
Nitrogen loss from laser welding melts pools and can have a deleterious effect on weld toughness for duplex stainless steels. This effect can be alleviated by using nitrogen as the shielding gas during laser welding. The use of nitrogen results in increased austenite levels in the weld metal and improved toughness levels.
PDF
