The Experts below are selected from a list of 291123 Experts worldwide ranked by ideXlab platform
Anne K Ellis - One of the best experts on this subject based on the ideXlab platform.
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clinical validation of controlled grass pollen challenge in the Environmental Exposure unit eeu
Allergy Asthma & Clinical Immunology, 2015Co-Authors: Anne K Ellis, Lisa M Steacy, Barnaby Hobsbawn, Caroline E Conway, Terry J WalkerAbstract:Rationale The Environmental Exposure Unit (EEU), a controlled allergen Exposure model of allergic rhinitis (AR), has traditionally utilized ragweed pollen. We sought to clinically validate the use of grass pollen in the EEU.
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onset of action efficacy and safety of a single dose of fexofenadine hydrochloride for ragweed allergy using an Environmental Exposure unit
Annals of Allergy Asthma & Immunology, 1997Co-Authors: Maureen P Briscoe, Anne K Ellis, April Welsh, Jeffrey Norman Smith, Adrian Clark, Jolene MasonAbstract:Background Fexofenadine hydrochloride is the active acid metabolite of terfenadine. Fexofenadine's antiallergic properties require confirmation in a clinical setting. Objective The purpose of this study was to characterize the time to onset of clinically important relief of symptoms of allergic rhinitis in subjects taking single doses of either 60 mg or 120 mg fexofenadine HCl, or placebo, after Exposure to ragweed pollen in a controlled environment. Other objectives were to assess the efficacy and safety of single doses of fexofenadine HCl. Methods One hundred forty-six ragweed-sensitive subjects were primed in the off-season with ragweed pollen in the Environmental Exposure unit. One hundred thirty-six subjects who adequately responded to priming entered a single-dose placebo phase. Placebo-responders were disqualified from the study, leaving 99 subjects with adequate symptoms to be randomized and given a single dose of either fexofenadine HCl 120 mg (33), 60 mg (33), or placebo (33) after 60 minutes of allergen Exposure. Exposure continued over five hours and subjects recorded symptoms every 20 minutes. This study was of a randomized, placebo-controlled, double-blind, parallel design. Results Median time to onset for relaxed criteria clinically important relief was 60 minutes for both fexofenadine treatment groups, and 100 minutes for placebo ( P = .018). The proportion with relief was 82% at 60 mg, 85% at 120 mg, and 64% for placebo. Treated groups had reductions in symptom scores double that of placebo. Conclusions Fexofenadine is safe and efficacious at single doses of 60 mg and 120 mg. Average time to onset was 60 minutes using controlled pollen Exposure in an Environmental Exposure units.
Norbert Krug - One of the best experts on this subject based on the ideXlab platform.
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effect of loteprednol etabonate nasal spray suspension on seasonal allergic rhinitis assessed by allergen challenge in an Environmental Exposure unit
Allergy, 2005Co-Authors: Norbert Krug, Jens M Hohlfeld, H Geldmacher, M Larbig, R Heermann, N Lavallee, D T Nguyen, U Petzold, Robert HermannAbstract:Background: Loteprednol etabonate (LE) is a novel soft steroid that was designed to improve the benefit/risk ratio of topical corticosteroid therapy. This study assesses the clinical efficacy and safety of three different doses of LE nasal spray in seasonal allergic rhinitis (SAR). Methods: In this single-center, double-blind, placebo-controlled, parallel-group trial 165 subjects with SAR to grass pollen received daily single doses of either 100, 200, 400 μg LE nasal spray, or placebo for 14 days. The patients underwent three 4-h allergen challenges with grass pollen in an Environmental Exposure unit at a screening visit (baseline) and on days 7 and 14 of treatment. Standardized nasal symptom scores were obtained every 20 min. Nasal flow, nasal secretions, and FEV1 were measured every hour during allergen challenges. Results: After 14 days of treatment, patients who received 400 μg LE had significantly lower total nasal symptom scores compared with those receiving placebo (P = 0.007). LE400 reduced rhinorrhea, nasal congestion, nasal itching, the amount of nasal secretions, and improved nasal flow as compared with placebo (P < 0.05). LE100 and LE200 were not significantly different from placebo. All treatments were well tolerated. Conclusions: Loteprednol 400 μg once daily is superior to placebo and the only effective dose tested in improving nasal symptoms and objective parameters in patients with SAR.
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validation of an Environmental Exposure unit for controlled human inhalation studies with grass pollen in patients with seasonal allergic rhinitis
Clinical & Experimental Allergy, 2003Co-Authors: Norbert Krug, Jens M Hohlfeld, H Geldmacher, M Larbig, H Loedding, A Buckendahl, Philipp Badorrek, W Behnke, Wilhelm Dunkhorst, Horst WindtAbstract:Summary Background There is an increasing need for allergen inhalation systems to perform basic clinical research and test anti-allergic drugs under well-controlled conditions. This requires stability of Environmental conditions like temperature and humidity, as well as allergen concentration and reproducible induction of allergic symptoms. Objective The aim of this study was to validate an Environmental Exposure unit for controlled human pollen inhalation studies in participants with seasonal allergic rhinitis. Methods Temperature, relative humidity, and air flow rate were kept constant with an air conditioning system. Pollen atmosphere was generated using a specially designed feeding system and monitored online by laser counter and offline using rotating rod samplers. Efficacy (total nasal symptom score, nasal air flow rate, nasal secretion) and safety (lung function) parameters were evaluated at different pollen concentrations and repeated allergen challenges. Results Temperature, humidity, and air flow rate in the Environmental Exposure unit remained constant within a range of <2%. The spatial distribution and the temporal stability of the pollen concentration varied only slightly over 4 h (±10% and <4%, respectively). Dose-dependent induction of allergic rhinitis symptoms, reduction in nasal air flow rate, and increase in nasal secretion were observed over time. These effects were reproducible from day to day. Lung function remained clinically normal at all concentrations and from day to day. Conclusions Thus, pollen Exposure in the Environmental Exposure unit is an effective, reproducible, safe, and suitable method for single-centre clinical studies on the efficacy of anti-allergic treatment or basic clinical research.
Terry J Walker - One of the best experts on this subject based on the ideXlab platform.
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clinical validation of controlled grass pollen challenge in the Environmental Exposure unit eeu
Allergy Asthma & Clinical Immunology, 2015Co-Authors: Anne K Ellis, Lisa M Steacy, Barnaby Hobsbawn, Caroline E Conway, Terry J WalkerAbstract:Rationale The Environmental Exposure Unit (EEU), a controlled allergen Exposure model of allergic rhinitis (AR), has traditionally utilized ragweed pollen. We sought to clinically validate the use of grass pollen in the EEU.
Tim S Nawrot - One of the best experts on this subject based on the ideXlab platform.
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Environmental Exposure to human carcinogens in teenagers and the association with DNA damage
Environmental research, 2016Co-Authors: Carmen Franken, Gudrun Koppen, Nathalie Lambrechts, Eva Govarts, Liesbeth Bruckers, Elly Den Hond, Ilse Loots, Vera Nelen, Isabelle Sioen, Tim S NawrotAbstract:Abstract Background We investigated whether human Environmental Exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Material and methods Six hundred 14–15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal Exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for Exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid as a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish Exposure-response relationships. Results Biomarkers of Exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter Exposure biomarkers were also associated with higher fish intake. Urinary nickel and t,t-muconic acid were inversely associated with the alkaline comet assay. Conclusion This cross-sectional study found associations between current Environmental Exposure to (potential) human carcinogens in 14–15-year-old Flemish adolescents and short-term (oxidative) damage to DNA. Prospective follow-up will be required to investigate whether long-term effects may occur due to complex Environmental Exposures.
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bone resorption and Environmental Exposure to cadmium in women a population study
Environmental Health Perspectives, 2008Co-Authors: Rudolph Schutte, Harry Roels, Lutgarde Thijs, Tim S Nawrot, Tom Richart, Dirk Vanderschueren, Tatiana Kuznetsova, Etienne Van Hecke, Jan A StaessenAbstract:BACKGROUND: Environmental Exposure to cadmium decreases bone density indirectly through hypercalciuria resulting from renal tubular dysfunction. OBJECTIVE: We sought evidence for a direct osteotoxic effect of cadmium in women. METHODS: We randomly recruited 294 women (mean age, 49.2 years) from a Flemish population with Environmental cadmium Exposure. We measured 24-hr urinary cadmium and blood cadmium as indexes of lifetime and recent Exposure, respectively. We assessed the multivariate-adjusted association of Exposure with specific markers of bone resorption, urinary hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), as well as with calcium excretion, various calciotropic hormones, and forearm bone density. RESULTS: In all women, the effect sizes associated with a doubling of lifetime Exposure were 8.4% (p = 0.009) for HP, 6.9% (p = 0.10) for LP, 0.77 mmol/day (p = 0.003) for urinary calcium, -0.009 g/cm(2) (p = 0.055) for proximal forearm bone density, and -16.8% (p = 0.065) for serum parathyroid hormone. In 144 postmenopausal women, the corresponding effect sizes were -0.01223 g/cm(2) (p = 0.008) for distal forearm bone density, 4.7% (p = 0.064) for serum calcitonin, and 10.2% for bone-specific alkaline phosphatase. In all women, the effect sizes associated with a doubling of recent Exposure were 7.2% (p = 0.001) for urinary HP, 7.2% (p = 0.021) for urinary LP, -9.0% (p = 0.097) for serum parathyroid hormone, and 5.5% (p = 0.008) for serum calcitonin. Only one woman had renal tubular dysfunction (urinary retinol-binding protein > 338 mu g/day). CONCLUSIONS: In the absence of renal tubular dysfunction, Environmental Exposure to cadmium increases bone resorption in women, suggesting a direct osteotoxic effect with increased calciuria and reactive changes in calciotropic hormones.
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Environmental Exposure to cadmium and risk of cancer a prospective population based study
Lancet Oncology, 2006Co-Authors: Tim S Nawrot, Harry Roels, Lutgarde Thijs, Jaco Vangronsveld, Etienne Van Hecke, Michelle Plusquin, Janneke G F Hogervorst, Hilde Celis, Jan A StaessenAbstract:Summary Background Cadmium is a ubiquitous Environmental pollutant, which accumulates in the human body such that 24-h urinary excretion is a biomarker of lifetime Exposure. We aimed to assess the association between Environmental Exposure to cadmium and cancer. Methods We recruited a random population sample (n=994) from an area close to three zinc smelters and a reference population from an area with low Exposure to cadmium. At baseline (1985–89), we measured cadmium in urine samples obtained over 24 h and in the soil of participants' gardens, and followed the incidence of cancer until June 30, 2004. We used Cox regression to calculate hazard ratios for cancer in relation to internal (ie, urinary) and external (ie, soil) Exposure to cadmium, while adjusting for covariables. Findings Cadmium concentration in soil ranged from 0·8 mg/kg to 17·0 mg/kg. At baseline, geometric mean urinary cadmium excretion was 12·3 nmol/day for people in the high-Exposure area, compared with 7·7 nmol/day for those in the reference (ie, low-Exposure) area (p Interpretation Historical pollution from non-ferrous smelters continues to present a serious health hazard, necessitating targeted preventive measures.
Jan A Staessen - One of the best experts on this subject based on the ideXlab platform.
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bone resorption and Environmental Exposure to cadmium in women a population study
Environmental Health Perspectives, 2008Co-Authors: Rudolph Schutte, Harry Roels, Lutgarde Thijs, Tim S Nawrot, Tom Richart, Dirk Vanderschueren, Tatiana Kuznetsova, Etienne Van Hecke, Jan A StaessenAbstract:BACKGROUND: Environmental Exposure to cadmium decreases bone density indirectly through hypercalciuria resulting from renal tubular dysfunction. OBJECTIVE: We sought evidence for a direct osteotoxic effect of cadmium in women. METHODS: We randomly recruited 294 women (mean age, 49.2 years) from a Flemish population with Environmental cadmium Exposure. We measured 24-hr urinary cadmium and blood cadmium as indexes of lifetime and recent Exposure, respectively. We assessed the multivariate-adjusted association of Exposure with specific markers of bone resorption, urinary hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), as well as with calcium excretion, various calciotropic hormones, and forearm bone density. RESULTS: In all women, the effect sizes associated with a doubling of lifetime Exposure were 8.4% (p = 0.009) for HP, 6.9% (p = 0.10) for LP, 0.77 mmol/day (p = 0.003) for urinary calcium, -0.009 g/cm(2) (p = 0.055) for proximal forearm bone density, and -16.8% (p = 0.065) for serum parathyroid hormone. In 144 postmenopausal women, the corresponding effect sizes were -0.01223 g/cm(2) (p = 0.008) for distal forearm bone density, 4.7% (p = 0.064) for serum calcitonin, and 10.2% for bone-specific alkaline phosphatase. In all women, the effect sizes associated with a doubling of recent Exposure were 7.2% (p = 0.001) for urinary HP, 7.2% (p = 0.021) for urinary LP, -9.0% (p = 0.097) for serum parathyroid hormone, and 5.5% (p = 0.008) for serum calcitonin. Only one woman had renal tubular dysfunction (urinary retinol-binding protein > 338 mu g/day). CONCLUSIONS: In the absence of renal tubular dysfunction, Environmental Exposure to cadmium increases bone resorption in women, suggesting a direct osteotoxic effect with increased calciuria and reactive changes in calciotropic hormones.
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Environmental Exposure to cadmium and risk of cancer a prospective population based study
Lancet Oncology, 2006Co-Authors: Tim S Nawrot, Harry Roels, Lutgarde Thijs, Jaco Vangronsveld, Etienne Van Hecke, Michelle Plusquin, Janneke G F Hogervorst, Hilde Celis, Jan A StaessenAbstract:Summary Background Cadmium is a ubiquitous Environmental pollutant, which accumulates in the human body such that 24-h urinary excretion is a biomarker of lifetime Exposure. We aimed to assess the association between Environmental Exposure to cadmium and cancer. Methods We recruited a random population sample (n=994) from an area close to three zinc smelters and a reference population from an area with low Exposure to cadmium. At baseline (1985–89), we measured cadmium in urine samples obtained over 24 h and in the soil of participants' gardens, and followed the incidence of cancer until June 30, 2004. We used Cox regression to calculate hazard ratios for cancer in relation to internal (ie, urinary) and external (ie, soil) Exposure to cadmium, while adjusting for covariables. Findings Cadmium concentration in soil ranged from 0·8 mg/kg to 17·0 mg/kg. At baseline, geometric mean urinary cadmium excretion was 12·3 nmol/day for people in the high-Exposure area, compared with 7·7 nmol/day for those in the reference (ie, low-Exposure) area (p Interpretation Historical pollution from non-ferrous smelters continues to present a serious health hazard, necessitating targeted preventive measures.
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Environmental Exposure to cadmium forearm bone density and risk of fractures prospective population study
The Lancet, 1999Co-Authors: Jan A Staessen, Harry Roels, Dmitri Emelianov, Tatyana Kuznetsova, Lutgarde Thijs, Jaco Vangronsveld, Robert FagardAbstract:Background Chronic low-level Exposure to cadmium may promote calcium loss via urinary excretion. We undertook a prospective population study to investigate whether Environmental Exposure to cadmium lowers bone density and increases risk of fractures. Methods We measured urinary cadmium excretion, a biomarker of lifetime Exposure, in people from ten districts of Belgium, of which six districts bordered on three zinc smelters. We also measured cadmium in soil and in vegetables from the districts, and collected data on incidence of fractures and height loss. Bone density was measured at the forearm just above the wrist by single photon absorptiometry, and calculated as the mean of six proximal and four distal scans. Findings Mean cadmium excretion at baseline was 8.7 nmol dairy. Across the ten districts, mean cadmium concentration in soil ranged from 0.8 to 14.7 mg/kg, and from 0.1 to 4.0 mg/kg dry weight in vegetables. Median follow-up was 6.6 years. Mean forearm bane density in proximal and distal scans was 0.54 g/cm(2) and 0.43 g/cm(2) in men, and 0.44 g/cm(2) and 0.34 g/cm(2) in women, in postmenopausal women, a twofold increase in urinary cadmium correlated with 0.01 g/cm(2) decrease in bone density (p < 0.02). The relative risks associated with doubted urinary cadmium were 1.73 (95% CI 1.16-2.57; p = 0.007) for fractures in women and 1.60 (0.94-2.72, p = 0.08) for height toss in men. Cadmium excretion in districts near smelters was 22.8% higher (p = 0.001) than in other districts, with fracture rates of 16.0 end 10.3 cases per 1000 person-years, respectively, and a population-attributable risk of 35.0%. Interpretation Even at a low degree of Environmental Exposure, cadmium may promote skeletal demineralisation, which may lead to increased bone fragility and raised risk of fractures.
