Publications by authors named "Leonard Siew"

Background: Immediate IgE-mediated hypersensitivity reactions to polyethylene glycol (PEG) are rare. Our understanding of PEG hypersensitivity is limited.

Objective: To evaluate the clinical characteristics and investigation outcomes of the largest cohort of patients with PEG allergy reported.

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Background: Vitamin B (Vit B) deficiency affects approximately 20% of those above the age of 60 years in the United Kingdom and United States. If untreated, it leads to detrimental health outcomes.

Objective: To investigate a cohort of patients with Vit B hypersensitivity (VB12H) referred to 3 UK allergy centers and design a pathway for the investigation of VB12H.

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Background: Dysregulated inflammatory responses and oxidative stress are key pathogenic drivers of chronic inflammatory diseases such as liver cirrhosis (LC). Regulatory T cells (Tregs) are essential to prevent excessive immune activation and maintain tissue homeostasis. While inflammatory cues are well known to modulate the function and stability of Tregs, the extent to which Tregs are influenced by oxidative stress has not been fully explored.

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Background: The emerging role of sphingosine-1-phosphate (S1P) in regulating smooth muscle functions has led to the exploration of the possibility that this sphingolipid could represent a potential therapeutic target in asthma and other lung diseases. Several studies in animal surrogates have suggested a role for S1P-mediated signaling in the regulation of airway smooth muscle (ASM) contraction, airway hyperresponsiveness, and airway remodeling, but evidence from human studies is lacking.

Objective: We sought to compare the responsiveness of the airways to S1P in healthy and asthmatic individuals in vivo, in isolated human airways ex vivo, and in murine airways dissected from healthy and house dust mite (HDM)-sensitized animals.

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Background: Pollen from grasses and trees can trigger allergic rhinitis (AR), where the symptoms and associated consequences can negatively affect quality of life (QoL). The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) is frequently used in clinical trials of AR to assess QoL. To help interpret RQLQ data, the minimal important difference (MID) can be used to assess whether a mean difference in QoL between treatment groups is clinically meaningful.

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Background: Piperacillin/tazobactam is a broad-spectrum penicillin. Hypersensitivity reactions are less commonly reported than with other penicillins except in patients with cystic fibrosis.

Objective: Detailed clinical characterization of a patient cohort referred with suspected piperacillin-tazobactam hypersensitivity.

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Background: The outbreak of the COVID-19 pandemic facilitated a rapid transition to non-face-to-face models of care across the allergy services.

Objective: To describe the outcomes of the use of synchronous telemedicine for outpatient consultations in a tertiary adult allergy center.

Methods: We retrospectively reviewed all non-face-to-face appointments during the second month of the pandemic in the United Kingdom.

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Background: We report a case of IgE-mediated hypersensitivity to lemon seed. We demonstrate for the first time a pattern of cross-sensitisation between seeds of citrus hybrid species from similar ancestral species origins.

Case Report: Described is a case of a 26-year-old female with recurrent anaphylaxis on exposure to lemon seed with sensitisation shown on prick to prick testing.

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Optic neuropathies are a group of optic nerve (ON) diseases caused by various insults including glaucoma, inflammation, ischemia, trauma, and genetic deficits, which are characterized by retinal ganglion cell (RGC) death and ON degeneration. An increasing number of genes involved in RGC intrinsic signaling have been found to be promising neural repair targets that can potentially be modulated directly by gene therapy, if we can achieve RGC specific gene targeting. To address this challenge, we first used adeno-associated virus (AAV)-mediated gene transfer to perform a low-throughput screening in both male and female mouse eyes and identified the mouse γ-synuclein (mSncg) promoter, which specifically and potently sustained transgene expression in mouse RGCs and also works in human RGCs.

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Introduction: Beta-lactams (BL) are the most frequently reported drug allergy, but the vast majority of patients are found not to be genuinely allergic after evaluation. Few studies have investigated the clinical predictors of genuine BL allergy, and the prevalence in hospitalized Chinese patients is unknown.

Methods: Patients admitted to a tertiary hospital in Hong Kong (HK) were analyzed to identify the prevalence and factors associated with the presence of BL allergy labels among hospitalized Chinese patients.

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Background: There are marked geographical as well as temporal differences in patient sensitization profiles to β-lactams (BL).

Objective: To determine the utility of skin test reagents and identify a cohort of patients where skin testing can be safely omitted in a cohort of patients referred to a UK tertiary referral center.

Methods: A retrospective study of the clinical characteristics of 1092 patients referred for BL allergy testing was analyzed using multivariate regression analysis.

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Background: Flucloxacillin is a narrow-spectrum, beta-lactamase-resistant penicillin. Type I (IgE-mediated) and type IV (T-cell-mediated) reactions are less frequently reported than with other penicillins.

Objective: To undertake a detailed clinical characterization of a cohort of patients referred with suspected flucloxacillin hypersensitivity.

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Neurotropic viruses, such as the rabies virus (RABV) and Japanese encephalitis virus (JEV), induce neuronal dysfunction and complication, causing neuronal damage. Currently, there are still no effective clinical treatments for neuronal injury caused by neurotropic viruses. Memantine, a drug capable of passing through the blood-brain barrier, noncompetitively and reversibly binds to n-methyl- d-aspartic acid (NMDA) receptors.

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Background: p38 mitogen-activated protein kinase (MAPK) plays a central role in the regulation and activation of pro-inflammatory mediators. COPD patients have increased levels of activated p38 MAPK, which correlate with increased lung function impairment, alveolar wall inflammation, and COPD exacerbations.

Objectives: These studies aimed to assess the effect of p38 inhibition with AZD7624 in healthy volunteers and patients with COPD.

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Background: Inhaled LPS causes neutrophilic airway inflammation in healthy subjects. We compared the effects of p38 MAPK inhibitors and fluticasone propionate on the LPS response.

Methods: Three randomised, double-blind, placebo-controlled, single dose crossover studies were performed.

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Objectives: The aim of this Phase 1, open-label study (NCT01395420) was to measure and compare concentrations of ceftazidime and avibactam in bronchial epithelial lining fluid (ELF) and plasma, following administration of two different dosing regimens in healthy subjects.

Patients And Methods: Healthy volunteers received 2000 mg of ceftazidime + 500 mg of avibactam (n = 22) or 3000 mg of ceftazidime + 1000 mg of avibactam (n = 21), administered intravenously every 8 h for 3 days (total of nine doses). Bronchoscopy with bronchoalveolar lavage was performed once per subject, 2, 4, 6 or 8 h after the last infusion.

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Thymic stromal lymphopoietin (TSLP) primes dendritic cells to promote a Th2 inflammatory response. Its action is mediated by a heterodimeric receptor which consists of the interleukin-7 receptor alpha chain and the TSLP receptor chain (TSLPR). TSLPR resembles the common gamma chain subunit utilized by many type 1 cytokine receptors.

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Phenotypic modulation of airway smooth muscle (ASM) is an important feature of airway remodeling in asthma that is characterized by enhanced proliferation and secretion of pro-inflammatory chemokines. These activities are regulated by the concentration of free Ca(2+) in the cytosol ([Ca(2+)](i)). A rise in [Ca(2+)](i) is normalized by rapid reuptake of Ca(2+) into sarcoplasmic reticulum (SR) stores by the sarco/endoplasmic reticulum Ca(2+) (SERCA) pump.

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