A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the ...definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, −0.5, and −1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: “GLILD is a distinct clinico-radio-pathological ILD occurring in patients with common variable immunodeficiency disorders, associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded.” There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51).
Optimal acetabular component orientation in total hip arthroplasty (THA) is a necessity in achieving a stable implant. Although there has been considerable debate in the literature concerning the ...safe zone, to date, there has not been any review to determine if these references are consistent with the definition applied by Lewinnek et al. in 1978. Therefore, this article aims to examine the available literature in the PubMed database to determine how often a correct reference to the safe zone as defined by Lewinnek was applied to discussions regarding THA.
A search for literature in the PubMed database was performed for articles from 1978 to 2019. Search criteria included terms ‘Lewinnek,’ ‘safe zone,’ and ‘total hip arthroplasty.’ Exclusions included abstract-only articles, non-English articles, articles unrelated to THA, and those lacking full content.
A review of literature yielded 147 articles for inclusion. Overall, only 11% (17) cited the Lewinnek article correctly. Forty-five percent (66) of articles referenced measurements in the supine position, 18% (26) referenced other positions, and 37% (55) did not specify. Nineteen percent (28) reported measurements of the acetabular cup orthogonal to the anterior pelvic plane, while 73% (108) did not, and 7% (11) did not specify. Twenty-three percent (34) measured from computed tomography scans instead of other methods.
In the discussion of the safe zone regarding THA, only 11% of articles listed are consistent with the definition established by Lewinnek. This warrants further investigation into a consistent application of the term and its implications for THA implant stability and dislocation rates.
Histamine (0.004–2
μ
M
) induced a concentration‐dependent shape change of human eosinophils, but not of neutrophils or basophils, detected as an increase in forward scatter (FSC) in the gated ...autofluorescence/forward scatter (GAFS) assay.
The histamine‐induced eosinophil shape change was completely abolished by thioperamide (10
μ
M
), an H
3
/H
4
receptor antagonist, but was not inhibited by pyrilamine or cimetidine (10
μ
M
), H
1
and H
2
receptor antagonists, respectively. The H
4
receptor agonists, clobenpropit and clozapine (0.004–2
μ
M
), which are also H
3
receptor antagonists, both induced eosinophil shape change, which was inhibited by thioperamide (10
μ
M
). The H
3
/H
4
receptor agonists, imetit,
R
‐
α
‐methyl histamine and
N
‐
α
‐methyl histamine (0.004–2
μ
M
) also induced eosinophil shape change.
Histamine induced actin polymerisation (0.015–10
μ
M
), intracellular calcium mobilisation (10–100
μ
M
) and a significant upregulation of expression of the cell adhesion molecule CD11b (0.004–10
μ
M
) in eosinophils, all of which were inhibited by thioperamide (10–100
μ
M
). In addition, the H
4
receptor agonist/H
3
receptor antagonist clozapine (20
μ
M
) stimulated a rise in intracellular calcium in eosinophils.
Activation of H
4
receptors by histamine (1
μ
M
) primed eosinophils for increased chemotactic responses to eotaxin, but histamine (0.1–10
μ
M
) did not directly induce chemotaxis of eosinophils.
Pertussis toxin (1
μ
g ml
−1
) inhibited shape change and actin polymerisation responses induced by histamine showing that these effects are mediated by coupling to a G
α
i/o
G‐protein.
This study demonstrates that human eosinophils express functional H
4
receptors and may provide a novel target for allergic disease therapy.
British Journal of Pharmacology
(2003)
140
, 1117–1127. doi:
10.1038/sj.bjp.0705530
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