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  • 1
    ISSN: 1539-6924
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Ethylene oxide is a gas produced in large quantities in the United States that is used primarily as a chemical intermediate in the production of ethylene glycol, propylene glycol, nonionic surfactants, ethanolamines, glycol ethers, and other chemicals. It has been well established that ethylene oxide can induce cancer, genetic, reproductive and developmental, and acute health effects in animals. The U.S. Environmental Protection Agency is currently developing both a cancer potency factor and a reference concentration (RfC) for ethylene oxide. This study used the rich database on the reproductive and developmental effects of ethylene oxide to develop a probabilistic characterization of possible regulatory thresholds for ethylene oxide. This analysis was based on the standard regulatory approach for noncancer risk assessment, but involved several innovative elements, such as: (1) the use of advanced statistical methods to account for correlations in developmental outcomes among littermates and allow for simultaneous control of covariates (such as litter size); (2) the application of a probabilistic approach for characterizing the uncertainty in extrapolating the animal results to humans; and (3) the use of a quantitative approach to account for the variation in heterogeneity among the human population. This article presents several classes of results, including: (1) probabilistic characterizations of ED10s for two quantal reproductive outcomes—resorption and fetal death, (2) probabilistic characterizations of one developmental outcome—the dose expected to yield a 5% reduction in fetal (or pup) weight, (3) estimates of the RfCs that would result from using these values in the standard regulatory approach for noncancer risk assessment, and (4) a probabilistic characterization of the level of ethylene oxide exposure that would be expected to yield a 1/1000 increase in the risk of reproductive or developmental outcomes in exposed human populations.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    BJOG 102 (1995), S. 0 
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 77 (1995), S. 2363-2369 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Using chemical-vapor deposition nanodispersed silicon has been prepared in carbon at temperatures between 850 and 1050 °C. Samples with up to 11% atomic silicon in carbon show the same pregraphitic x-ray-diffraction pattern as those without silicon. X-ray-absorption spectroscopy shows that the silicon is bonded mostly to carbon neighbors and that large clusters of silicon are not found. It is believed that silicon atoms, or small clusters of a few silicon atoms, are located in regions of "unorganized carbon'' which separate small regions of organized graphene layers. These materials may have application as electrode materials in advanced rechargeable lithium batteries. © 1995 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1520-5827
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background In vitro studies have shown much higher H 1 -receptor antagonist potency with desloratadine (DL) compared to fexofenadine (FEX), although it is unclear whether this has any clinical relevance on disease control parameters in seasonal allergic rhinitis (SAR), especially for nasal congestion.Objective To compare the relative efficacy between presently recommended doses of DL and FEX on daily measurements of peak nasal inspiratory flow (PNIF) and nasal symptoms in SAR.Methods Forty-nine patients with SAR were randomized into a double-blind, placebo-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 180 mg FEX or (b) 5 mg DL, taken in the morning. There was a 7–10 day placebo run-in and washout prior to each randomized treatment. Measurements were made in the morning (am) and in the evening (pm) for PNIF (the primary outcome variable), nasal and eye symptoms. The average of am/pm values were used for analysis.Results There were significant (P 〈 0.05) improvements, compared to placebo, with FEX and DL, for PNIF, nasal blockage, nasal irritation, and total nasal symptoms, but not nasal discharge or eye symptoms. There were no significant differences between active treatments. Values for PNIF (L/min) for mean placebo baseline, mean difference from baseline (95% CI for difference) were 126, 10 (4–16) for FEX; and 122, 11 (4–17) for DL. The mean difference (95% CI) between FEX vs. DL was 1 L/min (−7–8). Values for total nasal symptoms (out of 12) were: 3.2, 0.7 (0.2–1.2) for FEX; and 3.4, 0.9 (0.3–1.5) for DL, and for nasal blockage (out of 3) were: 1.1, 0.2 (0.1–0.4) for FEX; and 1.2, 0.3 (0.1–0.5) for DL. The mean difference (95% CI) in total nasal symptoms and nasal blockage between FEX vs. DL was 0.1 (−0.6–0.8) and 0.1 (−0.2–0.3), respectively.Conclusions Recommended once daily doses of fexofenadine and desloratadine were equally effective in improving nasal peak flow and nasal symptoms in SAR.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The combination of montelukast (ML) and loratadine (LT) has previously been shown to be superior to either drug alone in managing seasonal allergic rhinitis (SAR), whilst fexofenadine (FEX) has been shown to be better than LT as monotherapy.Objectives We wished to compare ML + LT vs. FEX alone for effects on daily measurements (am/pm) of peak inspiratory flow (PIF) and symptoms.Methods Thirty-seven patients with SAR (skin prick positive to grass pollen) were randomised into a single-blind, double-dummy placebo (PL)-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 120 mg FEX or (b) 10 mg ML + 10 mg LT. There was a 7–10 day placebo run-in and washout prior to each randomised treatment. The average of am/pm PIF (the primary outcome variable) was analysed. Patients recorded their symptom scores (from 0 to 3) twice daily, for nasal blockage, discharge, itching and sneezing with; total eye symptoms, ocular cromoglycate use, and daily activity. The total nasal symptom score was calculated as a composite (out of 24).Results There were no significant differences between baselines after the run-in and washout placebos for any variables. There were significant (P 〈 0.05, Bonferroni) improvements in all symptoms and PIF compared to pooled placebo with both treatments for all end-points, but no differences between the two treatment regimes (as means and within-treatment 95% confidence intervals): PIF: PL 102 (98–107), FEX 111 (107–116), ML + LT 113 (109–118); total nasal symptoms: PL 7.4 (6.7–2.0), FEX 5.0 (4.3–5.7), ML + LT 4.0 (3.3–4.7).Conclusions Once daily FEX as monotherapy was equally effective as the combination of once daily ML + LT in improving nasal peak flow and controlling symptoms in SAR. Further studies are indicated to assess whether ML confers additional benefits to FEX in SAR.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Airway hyper-responsiveness (AHR) to indirect stimuli is a useful non-invasive surrogate inflammatory marker in the evaluation of asthma, while histamine and cysteinyl leukotrienes are important inflammatory mediators.Objective To evaluate AHR to indirect bronchoconstrictor stimuli and time taken to recover following single doses of montelukast 10 mg and desloratadine 5 mg in combination, montelukast 10 mg alone and placebo.Methods Fifteen mild-to-moderate persistent asthmatics completed a randomized, double-blind, cross-over study. Patients received encapsulated montelukast 10 mg/desloratadine 5 mg combination, montelukast 10 mg alone and placebo, 10–14 h prior to challenge on two separate occasions. The mannitol threshold dose, AMP threshold concentration and recovery times after challenge were measured along with lung function.Results Compared to placebo, montelukast/desloratadine conferred improvements (P 〈 0.05) in adenosine monophosphate (AMP) threshold concentration and mannitol threshold dose: a 3.2-fold (95% CI 2.2–4.6) and 2.4-fold (95% CI 1.7–3.3) difference, respectively, while compared to montelukast this amounted to a 2.0-fold (95% CI 1.2–3.4) and 1.5-fold (95% CI 1.1–2.4) improvement, respectively. Montelukast was not significantly different from placebo. Both montelukast/desloratadine and montelukast compared to placebo, shortened recovery following both challenges (P 〈 0.05): a 27-min (95% CI 17–37) and 29-min (95% CI 20–36) reduction, respectively, for AMP, and a 27-min (95% CI 17–37) and 26-min (95% CI 17–35) reduction, respectively for mannitol.Conclusion The dissociated effects of single doses of montelukast alone but not montelukast/desloratadine combination on AHR and recovery time, highlights the relative roles of histamine in initiating the bronchoconstrictor response and cysteinyl leukotrienes in sustaining it. Similar improvements in AHR and recovery time were observed following both indirect bronchoconstrictor stimuli.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 31 (2001), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Allergic rhinitis and asthma commonly coexist and are both mediated by similar inflammatory mechanisms. Leukotriene antagonists may therefore be an alternative to corticosteroid therapy.Objective To compare oral montelukast with inhaled plus intranasal budesonide in patients with seasonal allergic rhinitis and asthma.Patients and methods A single-blind double-dummy placebo-controlled crossover study was performed comparing once daily 10 mg oral montelukast with 400 µg inhaled plus 200 µg intranasal budesonide in 12 patients with allergic rhinitis and asthma: mean (S.E.) age 34.0 years (2.7), forced expiratory volume in 1 s (FEV1) 91.2 (3.8)% predicted. Each treatment was for 2 weeks with a 1-week placebo run-in and washout. Measurements were made after each active treatment and placebo for: adenosine monophosphate bronchial challenge, exhaled and nasal nitric oxide. Patients also recorded their domiciliary peak expiratory flow, nasal peak inspiratory flow, asthma and seasonal allergic rhinitis symptoms.Results There were no significant differences between the placebos for any measurement. For adenosine monophosphate PC20, geometric mean fold differences (95% confidence interval (CI) for difference) were 6.4 (2.2–18.6) for placebo vs. budesonide, 2.9 (1.0–8.4) for placebo vs. montelukast, and 2.1 (1.1–4.5) for budesonide vs. montelukast. For exhaled nitric oxide (p.p.b.) there was significant (P 〈 0.05) suppression with both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For nasal nitric oxide and nasal peak flow there were only significant differences with budesonide compared with placebo. Both treatments reduced total seasonal allergic rhinitis symptoms but only budesonide had a significant effect on nasal symptoms.Conclusion Once-daily inhaled plus intranasal budesonide and once daily montelukast showed comparable efficacy on lower airway, but only the budesonide had significant efficacy on upper airway inflammatory markers. Both treatments significantly reduced allergic rhinitis symptoms.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The combination of a leukotriene receptor antagonist with an antihistamine may have beneficial effects in seasonal allergic rhinitis (SAR).To determine how combined oral mediator blockade compares to monotherapy with intranasal corticosteroid in the treatment of SAR.Twenty-two patients with seasonal allergic rhinitis were enrolled in a placebo controlled crossover study comparing 2 weeks therapy of either (a) 200 µg intranasal mometasone furoate (MF) once daily or (b) 10 mg oral montelukast plus 10 mg oral cetirizine once daily (MON/CZ), with a 7–10 day placebo period prior to each treatment period. Domiciliary measures of symptoms and nasal flow were recorded daily. Measurements of posterior rhinomanometry, acoustic rhinometry and nasal nitric oxide were made after all treatment and placebo periods.There were significant (P 〈 0.05) improvements in domiciliary peak nasal flow (l/min) with both MF (133 (3.8)) and MON/CZ (124 (3.8)) compared to pooled placebo (110 (4.0). Both treatments also showed significant improvement in terms of nasal blockage (units) (PL: 1.1(0.1), MF: 0.5 (0.1), MON/CZ 0.7 (0.1); and total nasal symptoms (units) (PL: 3.5 (0.3), MF 1.6 (0.3), MON/CZ 1.7 (0.3)), although there was no significant difference between the two active treatments. There were no significant differences between placebo and treatment for rhinomanometry, acoustic rhinometry or nitric oxide.Both intranasal mometasone furoate as monotherapy and oral cetirizine plus montelukast as cotherapy were equally effective for objective and subjective measures of treatment response in SAR. Domiciliary measurements of symptoms and peak flow were more sensitive than laboratory measurements of rhinomanometry, acoustic rhinometry and nasal nitric oxide.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1569-8041
    Keywords: low-dose continuous chemotherapy ; lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Although lymphoid malignancies are generallychemosensitive, relapse is common. The use of high-dose therapy can makesubsequent cytotoxic therapy intolerable. There is a need to develop regimenswith low acute toxicity which are suitable for use in patients post-high dosetherapy and following the failure of standard protocols. Patients and methods:Twenty-six patients with lymphomas, fifteenof whom had received high-dose therapy, were treated with a novel regimenconsisting of low-dose lomustine, chlorambucil, daily subcutaneous bleomycin,vincristine and methotrexate with dexamethasone on an eight-week cycle(LBCMVD-56). A median of three cycles was given. Results:The overall response rate at 12 weeks was 67%(21% complete remission (CR)) with a median overall survival of 13months. A symptomatic response was seen in 72%. Previous high-dosetherapy did not compromise the response rate. Toxicity was acceptable withgrade 3–4 haematological toxicity seen in 27% of cycles,gastrointestinal toxicity seen in 11% and pulmonary toxicity seen in8%. Thirty-one percent of patients required hospitalisation at somepoint during this treatment most commonly for neutropenic sepsis. Conclusions:LBCMVD-56 is an inexpensive, outpatient-based regimenwith low acute toxicity and a high response rate in this heavily pre-treatedgroup of patients.
    Type of Medium: Electronic Resource
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