ABSTRACT
Primary tumoral calcinosis is a rare and benign condition characterized by calcium salt deposition in periarticular soft tissues. It typically presents as a firm, rubbery mass that arises around large joints. While an estimated 250 cases have been described since its discovery, very few cases have been identified in the hand. We present a case of multiple calcified masses in the hand, one of which required meticulous dissection from a digital neurovascular bundle, and our technique for surgical excision. We present this case to lower the threshold for clinical suspicion of tumoral calcinosis for patients who present with a soft tissue mass in the hand. Furthermore, we recommend prompt surgical excision due to low success rates of alternative treatment options and to prevent potential neurovasculature or tendon injury.
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BACKGROUND: The clinical efficacy and safety of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) have been well-established; however, less is known about outcomes in patients undergoing preemptive ASA before transcatheter mitral valve replacement (TMVR). AIMS: The goal of this study is to characterize the procedural characteristics and examine the clinical outcomes of ASA in both HCM and pre-TMVR. METHODS: This retrospective study compared procedural characteristics and outcomes in patient who underwent ASA for HCM and TMVR. RESULTS: In total, 137 patients were included, 86 in the HCM group and 51 in the TMVR group. The intraventricular septal thickness (mean 1.8 vs. 1.2 cm; p < 0.0001) and the pre-ASA LVOT gradient (73.6 vs. 33.8 mmHg; p ≤ 0.001) were higher in the HCM group vs the TMVR group. The mean volume of ethanol injected was higher (mean 2.4 vs. 1.7 cc; p < 0.0001). The average neo-left ventricular outflow tract area increased significantly after ASA in the patients undergoing TMVR (99.2 ± 83.37 mm2 vs. 196.5 ± 114.55 mm2; p = <0.0001). The HCM group had a greater reduction in the LVOT gradient after ASA vs the TMVR group (49.3 vs. 18 mmHg; p = 0.0040). The primary composite endpoint was higher in the TMVR group versus the HCM group (50.9% vs. 25.6%; p = 0.0404) and had a higher incidence of new permanent pacemaker (PPM) (25.5% vs. 18.6%; p = 0.3402). The TMVR group had a higher rate of all-cause mortality (9.8% vs. 1.2%; p = 0.0268). CONCLUSIONS: Preemptive ASA before TMVR was performed in patients with higher degree of clinical comorbidities, and correspondingly is associated with worse short-term clinical outcomes in comparison to ASA for HCM patients. ASA before TMVR enabled percutaneous mitral interventions in a small but significant minority of patients that would have otherwise been excluded. The degree of LVOT and neoLVOT area increase is significant and predictable.
Subject(s)
Ablation Techniques , Cardiac Catheterization , Cardiomyopathy, Hypertrophic , Ethanol , Heart Valve Prosthesis Implantation , Mitral Valve , Humans , Retrospective Studies , Male , Ethanol/administration & dosage , Ethanol/adverse effects , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/mortality , Cardiomyopathy, Hypertrophic/therapy , Cardiomyopathy, Hypertrophic/surgery , Cardiomyopathy, Hypertrophic/physiopathology , Female , Treatment Outcome , Ablation Techniques/adverse effects , Ablation Techniques/mortality , Aged , Cardiac Catheterization/adverse effects , Cardiac Catheterization/mortality , Cardiac Catheterization/instrumentation , Middle Aged , Risk Factors , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/mortality , Time Factors , Mitral Valve/diagnostic imaging , Mitral Valve/physiopathology , Mitral Valve/surgery , Recovery of Function , Aged, 80 and over , Heart Septum/diagnostic imaging , Heart Septum/surgery , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/physiopathology , Mitral Valve Insufficiency/surgery , Mitral Valve Insufficiency/mortalityABSTRACT
Background: Asthma is a complex disease and a severe global public health problem resulting from interactions between genetic background and environmental exposures. It has been suggested that gut microbiota may be related to asthma development; however, such relationships needs further investigation. Objective: This study aimed to characterize the gut microbiota as well as the nasal lavage cytokine profile of asthmatic and nonasthmatic individuals. Methods: Stool and nasal lavage samples were collected from 29 children and adolescents with type 2 asthma and 28 children without asthma in Brazil. Amplicon sequencing of the stool bacterial V4 region of the 16S rRNA gene was performed using Illumina MiSeq. Microbiota analysis was performed by QIIME 2 and PICRUSt2. Type 2 asthma phenotype was characterized by high sputum eosinophil counts and positive skin prick tests for house dust mite, cockroach, and/or cat or dog dander. The nasal immune marker profile was assessed using a customized multiplex panel. Results: Stool microbiota differed significantly between asthmatic and nonasthmatic participants (P = .001). Bacteroides was more abundant in participants with asthma (P < .05), while Prevotella was more abundant in nonasthmatic individuals (P < .05). In people with asthma, the relative abundance of Bacteroides correlated with IL-4 concentration in nasal lavage samples. Inference of microbiota functional capacity identified differential fatty acid biosynthesis in asthmatic compared to nonasthmatic subjects. Conclusion: The stool microbiota differed between asthmatic and nonasthmatic young people in Brazil. Asthma was associated with higher Bacteroides levels, which correlated with nasal IL-4 concentration.
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Humans have lived from equator to poles for millennia but are now increasingly intruding into the wild spaces of other species and steadily extruding ourselves from our own wild spaces, with a profound impact on: our relationship with the natural world; survival of other species; pollution; climate change; etc. We have yet to grasp how these changes directly impact our own health. The primary focus of this paper is on the beneficial influence of proximity to the natural environment. We summarize the evidence for associations between exposure to green space and blue space and improvements in health. In contrast, grey space - the urban landscape - largely presents hazards as well as reducing exposure to green and blue space and isolating us from the natural environment. We discuss various hypotheses that might explain why green, blue, and grey space affect health and focus particularly on the importance of the biodiversity hypothesis and the role of microbiota. We discuss possible mechanisms and exposure routes - air, soil, and water. We highlight the problem of exposure assessment, noting that many of our current tools are not fit for the purpose of understanding exposure to green and blue space, aerosols, soils, and water. We briefly discuss possible differences between indigenous perspectives on the nature of our relationship with the environment and the more dominant international-science view. Finally, we present research gaps and discuss future directions, particularly focusing on the ways in which we might - even in the absence of a full understanding of the mechanisms by which blue, green, and grey space affect our health - begin to implement policies to restore some balance to our environment of with the aim of reducing the large global burden of ill health.
Subject(s)
Microbiota , Soil , Humans , Biodiversity , Environmental Pollution , Parks, RecreationalABSTRACT
BACKGROUND: Neural and remodeling mechanisms may play a role in asthma, particularly noneosinophilic asthma (NEA). OBJECTIVE: To assess sputum mediators associated with neural, remodeling, and inflammatory mechanisms in eosinophilic asthma (EA), NEA, and participants without asthma. METHODS: A total of 111 participants with and 62 without asthma (14-21 years old) underwent sputum induction, exhaled nitric oxide, atopy, and spirometry tests. There were 24 mediators measured in sputum using enzyme-linked immunosorbent assay or bead array. Eosinophilic asthma (n = 52) and NEA (n = 59) were defined using a sputum eosinophil level cut-point of greater than or equal to 2.5%. RESULTS: Elevated levels of nociceptin (median: 39.1 vs 22.4 ng/mL, P = .03), periostin (33.8 vs 9.4 ng/mL, P = .01), and ECP; (220.1 vs 83.7 ng/mL, P = .03) were found in patients with asthma compared with those without asthma. Nociceptin was elevated in EA (54.8 vs 22.4 ng/mL, P = .02) compared with participants without asthma. Eosinophilic asthma had higher levels of inflammatory mediators (ECP: 495.5 vs 100.3 ng/mL, P ≤ .01; interleukin-1ß: 285.3 vs 209.3 pg/mL, P = .03; histamine: 5805.0 vs 3172.5 pg/mL, P < .01) and remodeling mediators (VEGF-A); 3.3 vs 2.5 ng/mL, P = .03; periostin: 47.7 vs 22.1 ng/mL, P = .04) than NEA. Whereas macrophages were associated with neural mediators, for example, neurokinin A (r = 0.27, P = .01) and nociceptin (r = 0.30, P = .02), granulocytes were associated with inflammatory and remodeling mediators (eg, ECP and VEGF-A correlated with neutrophils (r = 0.53 and r = 0.33, respectively, P < .01) and eosinophils (r = 0.53 and r = 0.29 respectively, P ≤ .01). CONCLUSION: Elevated levels of nociceptin and inflammatory and remodeling markers were found in EA, but no evidence for neural and remodeling pathways was found in NEA. Neural and remodeling mechanisms seem to coexist with inflammation.
Subject(s)
Asthma , Pulmonary Eosinophilia , Humans , Adolescent , Young Adult , Adult , Sputum/metabolism , Vascular Endothelial Growth Factor A/metabolism , Eosinophils/metabolismABSTRACT
OBJECTIVE: An imbalance in autonomic nervous system (ANS) activity may play a role in asthma, but it is unclear whether this is associated with specific pathophysiology. This study assessed ANS activity by measuring heart rate variability (HRV) in eosinophilic (EA) and non-eosinophilic asthma (NEA) and people without asthma. METHODS: HRV, combined hypertonic saline challenge/sputum induction, exhaled nitric oxide (FeNO), skin prick tests to measure atopy, and spirometry tests were conducted in teenagers and young adults (14-21 years) with (n = 96) and without (n = 72) generally well-controlled asthma. HRV parameters associated with sympathetic and parasympathetic ANS branches were analyzed. EA and NEA were defined using a 2.5% sputum eosinophil cut-point. Airway hyperreactivity (AHR) was defined as ≥15% reduction in FEV1 following saline challenge. RESULTS: HRV parameters did not differ between asthmatics and non-asthmatics or EA and NEA. They were also not associated with markers of inflammation, lung function or atopy. However, increased absolute low frequency (LFµs2; representing increased sympathetic nervous system (SNS) activity) was found in asthmatics who used ß-agonist medication compared to those who did not (median: 1611, IQR 892-3036 vs 754, 565-1592; p < 0.05) and increased normalized low frequency (LF nu) was found in those with AHR compared to without AHR (64, 48-71 vs 53, 43-66; p < 0.05). CONCLUSION: ANS activity (as measured using HRV analysis) is not associated with pathophysiology or inflammatory phenotype in young asthmatics with generally well-controlled asthma. However, enhanced SNS activity can be detected in asthmatics with AHR or who use ß-agonist medication.
Subject(s)
Asthma , Pulmonary Eosinophilia , Humans , Asthma/diagnosis , Asthma/drug therapy , Heart Rate , Eosinophils , Autonomic Nervous System , Sputum , Nitric OxideABSTRACT
BACKGROUND: Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK). METHODS: We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016-20. All centres studied children and adolescents (age range 8-20 years), except the UK centre which involved 26-27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum. RESULTS: Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37-2.94) with lower odds in the LMICs: Brazil (0.73, 0.42-1.27), Ecuador (0.40, 0.24-0.66) and Uganda (0.62, 0.37-1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda. CONCLUSIONS: This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally.
Subject(s)
Asthma , Humans , Cross-Sectional Studies , Asthma/epidemiology , Asthma/drug therapy , Phenotype , Brazil/epidemiology , New Zealand/epidemiologyABSTRACT
Amyotrophic lateral sclerosis (ALS) is an incurable and rapidly progressive neurological disorder. Biomarkers are critical to understanding disease causation, monitoring disease progression and assessing the efficacy of treatments. However, robust peripheral biomarkers are yet to be identified. Neuroinflammation and breakdown of the blood-brain barrier (BBB) are common to familial and sporadic ALS and may produce a unique biomarker signature in peripheral blood. Using cytometric bead array (n = 15 participants per group (ALS or control)) and proteome profiling (n = 6 participants per group (ALS or control)), we assessed a total of 106 serum cytokines, growth factors, and BBB breakdown markers in the serum of control and ALS participants. Further, primary human brain pericytes, which maintain the BBB, were used as a biosensor of inflammation following pre-treatment with ALS serum. Principal components analysis of all proteome profile data showed no clustering of control or ALS sera, and no individual serum proteins met the threshold for statistical difference between ALS and controls (adjusted P values). However, the 20 most changed proteins between control and ALS sera showed a medium effect size (Cohen's d = 0.67) and cluster analysis of their levels together identified three sample subsets; control-only, mixed control-ALS, and ALS-only. These 20 proteins were predominantly pro-angiogenic and growth factors, including fractalkine, BDNF, EGF, PDGF, Dkk-1, MIF and angiopoietin-2. S100ß, a protein highly concentrated in glial cells and therefore a marker of BBB leakage when found in blood, was unchanged in ALS serum, suggesting that serum protein profiles were reflective of peripheral rather than CNS biofluids. Finally, primary human brain pericytes remained proliferative and their secretome was unchanged by chronic exposure to ALS serum. Our exploratory study suggests that individual serum cytokine levels may not be robust biomarkers in small studies of ALS, but that larger studies using multiplexed analysis of pro-angiogenic and growth factors may identify a peripheral signature of ALS pathogenesis.
Subject(s)
Amyotrophic Lateral Sclerosis , Amyotrophic Lateral Sclerosis/pathology , Biomarkers , Blood-Brain Barrier/metabolism , Cytokines , Humans , Intercellular Signaling Peptides and Proteins , Neuroinflammatory Diseases , Proteome/metabolismABSTRACT
Dust-exposed construction workers have an increased risk of respiratory symptoms, but the efficacy of dust-control measures remains unclear. This study compared respiratory symptoms, using a modified European Community Respiratory Health Survey questionnaire, between construction workers (n = 208) and a reference group of bus drivers and retail workers (n = 142). Within the construction workers, we assessed the effect of collective (on-tool vacuum/'wet-cut' systems) and personal (respirators) exposure controls on symptom prevalence. Logistic regression assessed differences between groups, adjusted for age, ethnicity, and smoking status. Construction workers were more likely to cough with phlegm at least once a week (OR 2.4, 95% CI 1.2-4.7) and cough with phlegm ≥3 months/year for ≥2 years (OR 2.8, CI 1.2-7.0), but they had similar or fewer asthma symptoms. Construction workers who had worked for 11-20 years reported more cough/phlegm symptoms (OR 5.1, 1.7-15.0 for cough with phlegm ≥3 months/year for ≥2 years) than those who had worked <10 years (OR 1.9, 0.6-5.8), when compared to the reference group. Those who used 'wet-cut' methods reported less cough with phlegm, although the evidence for this association was weak (OR 0.4, CI 0.2-1.1 for cough with phlegm at least once a week); use of on-tool extraction showed a similar trend. No associations between respiratory protective equipment-use and symptoms were found. In conclusion, construction workers reported more symptoms suggestive of bronchitis, particularly those employed in the industry for >10 years. Use of collective dust exposure controls might protect against these symptoms, but this requires confirmation in a larger study.
Subject(s)
Construction Industry , Occupational Diseases , Occupational Exposure , Cough/complications , Cough/epidemiology , Cross-Sectional Studies , Dust/analysis , Humans , New Zealand/epidemiology , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Occupational Diseases/prevention & control , Occupational Exposure/adverse effectsABSTRACT
Internationally, there is an effort to have schools adopt a whole-school approach to physical activity promotion. Such a model includes physical activity opportunities throughout the whole school day, including physical education; before, during, and after school physical activity; and staff and community engagement. The purpose of this study was to describe the physical activity experiences of young people attending secondary schools in Finland, Ireland, and the United States where a whole-school approach to physical activity promotion was employed. One school in each country was identified based on its adoption of a national physical activity initiative (i.e., Finland-Finnish Schools on the Move; Ireland-Active School Flag; United States-Let's Move Active Schools). Data were collected through observation with field notes, photos, and interviews with key stakeholders. The results are presented as analytic narrative vignettes that represent a "typical" school day. The results provide a glimpse into available physical activity opportunities for young people at each school and demonstrate an emphasis on active school culture.
Subject(s)
School Health Services , Schools , Adolescent , Exercise , Finland , Health Promotion/methods , Humans , Ireland , Students , United StatesABSTRACT
BACKGROUND: Neural mechanisms may play an important role in non-eosinophilic asthma (NEA). This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic asthma (EA) and NEA and non-asthmatics. METHODS: Thirty-eight asthmatics and 19 non-asthmatics (aged 14-21 years) underwent combined hypertonic saline challenge/sputum induction, fractional exhaled nitric oxide, atopy and spirometry tests, followed by capsaicin challenge. EA and NEA were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity was defined as a ≥15% drop in FEV1 during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs. RESULTS: Non-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared with non-asthmatics (n=19) (geometric mean C5: 58.3 µM, 95% CI 24.1 to 141.5 vs 193.6 µM, 82.2 to 456.0; p<0.05). NEA tended to also have greater capsaicin sensitivity than EA, with the difference in capsaicin sensitivity between NEA and EA being of similar magnitude (58.3 µM, 24.1 to 141.5 vs 191.0 µM, 70.9 to 514.0) to that observed between NEA and non-asthmatics; however, this did not reach statistical significance (p=0.07). FEV1 was significantly reduced from baseline following capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found between subgroups. No associations with capsaicin sensitivity and atopy, sputum eosinophils, blood eosinophils, asthma control or treatment were observed. CONCLUSION: NEA, but not EA, showed enhanced capsaicin sensitivity compared with non-asthmatics. Sensory nerve reactivity may therefore play an important role in the pathophysiology of NEA.
Subject(s)
Asthma , Pulmonary Eosinophilia , Eosinophils , Fractional Exhaled Nitric Oxide Testing , Humans , SputumABSTRACT
BACKGROUND: Cleaning is associated with an increased risk of asthma symptoms, but few studies have measured functional characteristics of airway disease in cleaners. AIMS: To assess and characterize respiratory symptoms and lung function in professional cleaners, and determine potential risk factors for adverse respiratory outcomes. METHODS: Symptoms, pre-/post-bronchodilator lung function, atopy, and cleaning exposures were assessed in 425 cleaners and 281 reference workers in Wellington, New Zealand between 2008 and 2010. RESULTS: Cleaners had an increased risk of current asthma (past 12 months), defined as: woken by shortness of breath, asthma attack, or asthma medication (OR = 1.83, 95% CI = 1.18-2.85). Despite this, they had similar rates of current wheezing (OR = 0.93, 95% CI = 0.65-1.32) and were less likely to have a doctor diagnosis of asthma ever (OR = 0.62, 95% CI = 0.42-0.92). Cleaners overall had lower lung function (FEV1 , FVC; P < .05). Asthma in cleaners was associated with less atopy (OR = 0.35, 95% CI = 0.13-0.90), fewer wheezing attacks (OR = 0.40, 95% CI = 0.17-0.97; >3 vs ≤3 times/year), and reduced bronchodilator response (6% vs 9% mean FEV1 -%-predicted change, P < .05) compared to asthma in reference workers. Cleaning of cafes/restaurants/kitchens and using upholstery sprays or liquid multi-use cleaner was associated with symptoms, whilst several exposures were also associated with lung function deficits (P < .05). CONCLUSIONS AND CLINICAL RELEVANCE: Cleaners are at risk of some asthma-associated symptoms and reduced lung function. However, as it was not strongly associated with wheeze and atopy, and airway obstruction was less reversible, asthma in some cleaners may represent a distinct phenotype.
Subject(s)
Asthma , Occupational Diseases , Occupational Exposure/adverse effects , Adult , Asthma/diagnosis , Asthma/etiology , Asthma/physiopathology , Female , Humans , Male , Middle Aged , Occupational Diseases/diagnosis , Occupational Diseases/physiopathology , Respiratory Function TestsABSTRACT
Activated NKT cells can stimulate antigen-presenting cells leading to enhanced peptide antigen-specific immunity. However, administration of potent NKT cell agonists like α-galactosylceramide (α-GalCer) can be associated with release of high levels of cytokines, and in some situations, hepatotoxicity. Here we show that it is possible to provoke sufficient NKT cell activity to stimulate strong antigen-specific T cell responses without these unwanted effects. This was achieved by chemically conjugating antigenic peptides to α-galactosylphytosphingosine (α-GalPhs), an NKT cell agonist with very weak activity based on structural characterisation and biological assays. Conjugation improved delivery to antigen-presenting cells in vivo, while use of a cathepsin-sensitive linker to release the α-GalPhs and peptide within the same cell promoted strong T cell activation and therapeutic anti-tumour responses in mice. The conjugates activated human NKT cells and enhanced human T cell responses to a viral peptide in vitro. Accordingly, we have demonstrated a means to safely exploit the immunostimulatory properties of NKT cells to enhance T cell activation for virus- and tumour-specific immunity.
Subject(s)
Antigen-Presenting Cells/immunology , Cancer Vaccines/administration & dosage , Natural Killer T-Cells/drug effects , Natural Killer T-Cells/immunology , Neoplasms, Experimental/immunology , Peptides/administration & dosage , Adjuvants, Immunologic , Animals , Antigens, CD1d/chemistry , Cancer Vaccines/immunology , Chemical and Drug Induced Liver Injury/prevention & control , Epitopes/chemistry , Glycolipids/chemistry , Lymphocyte Activation , Mice , Mice, Inbred C57BL , Neoplasms, Experimental/drug therapy , Peptides/chemistry , Peptides/immunologyABSTRACT
The World Asthma Phenotypes (WASP) study started in 2016 and has been conducted in five centres, in the UK, New Zealand, Brazil, Ecuador and Uganda. The objectives of this study are to combine detailed biomarker and clinical information in order to 1) better understand and characterise asthma phenotypes in high-income countries (HICs) and low and middle-income countries (LMICs), and in high and low prevalence centres; 2) compare phenotype characteristics, including clinical severity; 3) assess the risk factors for each phenotype; and 4) assess how the distribution of phenotypes differs between high prevalence and low prevalence centres. Here we present the rationale and protocol for the WASP study to enable other centres around the world to carry out similar analyses using a standardised protocol. Large collaborative and integrative studies like this are essential to further our understanding of asthma phenotypes. The findings of this study will help elucidate the aetiological mechanisms of asthma and might potentially identify new causes and guide the development of new treatments, thereby enabling better management and prevention of asthma in both HICs and LMICs.
ABSTRACT
OBJECTIVES: To conduct a cross-sectional morbidity survey among 245 former employees of a pesticide production plant exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in New Zealand. METHODS: Demographic factors and health information were collected in face-to-face interviews. TCDD, lipids, thyroid hormones, glucose and immunoglobulin G (IgG) were determined in non-fasting blood. For 111 participants, a neurological examination was conducted. Associations between health outcomes and working in a TCDD exposed job (prevalence 49%) and serum TCDD concentration≥10pg/g lipid (18%) were assessed using logistic regression whilst controlling for age, gender, smoking, body mass index and ethnicity. RESULTS: Diabetes was more common in those who had worked in TCDD exposed jobs (OR 4.0, 95%CI 1.0-15.4) and in those with serum TCDD ≥10pg/g (OR 3.1, 95%CI 0.9-10.7). Non-fasting glucose levels >6.6mmol/l were more common in those with TCDD exposed jobs (OR 3.6, 95%CI 1.0-12.9), as were serum free thyroxine 4<12.8pmol/l (OR 4.5, 95%CI 1.4-14.4), triglycerides >1.7mmol/l (OR 2.5, 95%CI 1.1-5.7) and high density lipoprotein cholesterol (HDL) <1mmol/l (OR 4.0, 95%CI 1.2-13.2). IgG was negatively associated with TCDD (linear regression p=0.05). The neurological examination revealed a higher frequency of abnormal reflexes in those with serum TCDD ≥10pg/g (OR 4.8, 95%CI 1.1-21.0). CONCLUSIONS: In this occupationally exposed population, TCDD was associated with an increased risk of diabetes and a range of subclinical responses in multiple systems (peripheral nervous system, immune system, thyroid hormones and lipid metabolism), several decades after last exposure. These results need to be interpreted with caution due to the small study size and the cross-sectional nature of the study.
Subject(s)
Occupational Diseases/epidemiology , Occupational Exposure/adverse effects , Pesticides/toxicity , Polychlorinated Dibenzodioxins/toxicity , Chemical Industry , Cross-Sectional Studies , Diabetes Mellitus, Type 2 , Female , Humans , Interviews as Topic , Logistic Models , Male , Middle Aged , New Zealand/epidemiology , Occupational Diseases/mortality , Pesticides/blood , Polychlorinated Dibenzodioxins/bloodABSTRACT
BACKGROUND: Asthma inflammatory phenotypes are often defined by relative cell counts of airway eosinophils/neutrophils. However, the importance of neutrophilia remains unclear, as does the effect of ICS treatment on asthma phenotypes and airway neutrophil function. The purpose of this study was to assess asthma phenotype prevalence/characteristics in a community setting, and, in a nested preliminary study, determine how treatment changes affect phenotype stability and inflammation, with particular focus on airway neutrophils. METHODS: Fifty adult asthmatics and 39 non-asthmatics were assessed using questionnaires, skin prick tests, spirometry, exhaled nitric oxide (FENO) measurement, and sputum induction. Twenty-one asthmatics underwent further assessment following treatment optimisation (n = 11) or sub-optimisation (n = 10). RESULTS: Forty percent (20/50) had eosinophilic asthma (EA) and 8% had neutrophilic asthma. EA was associated with increased FENO, bronchodilator reversibility (BDR) and reduced lung function (p < 0.05). Following optimisation/sub-optimisation, the EA/NEA (non-eosinophilic asthma) phenotype changed in 11/21 (52%) asthmatics. In particular, fewer subjects had EA post treatment optimisation, but this was not statistically significant. However, a significant (p < 0.05) reduction in FENO, ACQ7 score, and BDR was observed after treatment optimisation, as well as an increase in FEV1-% predicted (p < 0.05). It was also associated with reduced eosinophils (p < 0.05) and enhanced neutrophil phagocytosis (p < 0.05) in EA only, and enhanced neutrophil oxidative burst in both EA and NEA (p < 0.05). CONCLUSIONS: In this community based population, non-eosinophilic asthma was common, less severe than EA, and at baseline most asthmatics showed no evidence of inflammation. In the nested change in treatment study, treatment optimisation was associated with reduced sputum eosinophils, improved symptoms and lung function, and enhanced neutrophil function, but a significant reduction in EA could not be demonstrated. TRIAL REGISTRATION: The nested change in treatment component of this study is registered at the Australia and New Zealand Clinical Trial Registry ( www.ANZCTR.org.au ) ACTRN12617001356358 . Registration date 27/09/2017. Retrospectively registered.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Asthma/drug therapy , Bronchodilator Agents/therapeutic use , Eosinophilia/drug therapy , Neutrophils/physiology , Phenotype , Administration, Inhalation , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adult , Aged , Asthma/physiopathology , Breath Tests , Female , Forced Expiratory Volume , Humans , Inflammation/physiopathology , Male , Middle Aged , Nitric Oxide/analysis , Peak Expiratory Flow Rate , Phagocytosis , Respiratory Burst , Sputum/cytology , Surveys and Questionnaires , Young AdultABSTRACT
OBJECTIVES: Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has inconsistently been associated with a decreased sex ratio of the offspring (number of male births divided by total births). We conducted a study among men and women who were employed in a New Zealand phenoxy herbicide production plant between 1969 and 1984, to study their offspring sex ratio in relation to their back-calculated TCDD serum concentrations determined in 2007/2008. METHODS: A total of 127 men and 21 women reported that 355 children were conceived after starting employment at the plant. The association between their lipid-standardised TCDD serum concentrations back-calculated to the time of their offspring's birth and the probability of a male birth was estimated through logistic regression, adjusting for the age of the exposed parent at birth, current body mass index and smoking. RESULTS: The overall sex ratio was 0.55 (197 boys, 158 girls). For fathers with serum TCDD concentrations ≥20â pg/g lipid at time of birth, the sex ratio was 0.47 (OR 0.49; 95% CI 0.30 to 0.79). The probability of a male birth decreased with higher paternal serum TCDD at time of birth (<4; 4-20; 20-100; ≥100â pg/g lipid), with ORs of 1.00 (reference); 1.00 (95% CI 0.50 to 2.02); 0.52 (95% CI 0.29 to 0.92); 0.45 (95% CI 0.23 to 0.89), p trend 0.007. For exposed mothers, the sex ratio was not reduced. CONCLUSIONS: This study indicates that paternal serum TCDD concentrations in excess of an estimated 20â pg/g lipid at time of conception are associated with a reduced sex ratio.
Subject(s)
Dioxins/adverse effects , Occupational Exposure/adverse effects , Paternal Exposure/adverse effects , Sex Ratio , Adult , Body Mass Index , Cohort Studies , Dioxins/blood , Female , Herbicides/adverse effects , Humans , Industry , International Agencies , Interviews as Topic , Logistic Models , Male , Middle Aged , New Zealand , Pregnancy , Sex Distribution , Young AdultABSTRACT
Gastric glomus tumors are rare, mesenchymal neoplasms, generally described as benign and account for nearly 1% of all gastrointestinal soft tissue tumors. The most common gastrointestinal site of involvement is the stomach, particularly the antrum. Gastric glomus tumors are submucosal tumors that lack specific clinical and endoscopic characteristics, and are often mistaken for the more common gastrointestinal stromal tumors. A 62-year-old Caucasian female presented with shortness of breath and a persistent cough. Clinical workup revealed a mass in the upper abdomen. After endoscopic ultrasound and fine needle aspiration raised concerns for cancer, the patient elected to proceed with exploratory laparotomy. A local resection was performed at the time of surgery. Pathologic and immunohistochemical findings following surgical resection were consistent with a gastric glomus tumor. Consideration of gastric glomus tumors in the differential diagnosis may optimize the chance for a more accurate preoperative diagnosis and targeted surgical intervention.