Maximum Percent Decrease Research Articles

SU-E-J-117: Assessing Response to Radiochemotherapy Treatment On 18F-FDG PET in Non-Small Cell Lung Cancer Using Approaches of Histogram and Gray Level Co-Occurrence Matrix

Purpose: The aim of this study was to propose and investigate gray level histogram and texture features information provided by 18F-FDG PET to assess patients imaging response to radiochemotherapy in non-small cell lung cancer (NSCLC). Methods: Twelve patients with newly diagnosed NSCLC treated with combined radiochemotherapy were involved in this study. Patients were categorized under three headings (non-responders, partial responders and complete responders) by experienced radiologists on the basis of RECIST according PET scans changes between pretreatment and 1 month after treatment. We analyzed the percentage variation of PET density using histogram analysis approach which characterizes global change of tumor region on PET. Texture parameters variation between pretreatment and 1 month after treatment completion which describe local voxel spatial distribution were extracted from Gray Level Co-occurrence Matrix (GLCM). Correlation between characteristics variation and three type response status were analyzed. Results: The uniformity of gray level histogram on the whole and the maximum percentage decrease in histogram was well associated with tumor shrinkage and response status. The above indices derived from histogram were capable to differentiate three groups tumor response to radiochemotherapy. Texture parameters variation (ASM, ENT and IDM) were able to differentiate the 3 response groups considering a high correlation with response status. Conclusion: We demonstrated that histogram and texture analysis methods on baseline 18F-FDG PET scans provided robust, discriminative stratification in assessing response to combined radiochemotherapy and may have a good application prospect in clinical practice.

Numerical Simulation of Airfoil Aerodynamic Penalties and Mechanisms in Heavy Rain

Numerical simulations that are conducted on a transport-type airfoil, NACA 64-210, at a Reynolds number of2.6×106and LWC of 25 g/m3explore the aerodynamic penalties and mechanisms that affect airfoil performance in heavy rain conditions. Our simulation results agree well with the experimental data and show significant aerodynamic penalties for the airfoil in heavy rain. The maximum percentage decrease inCLis reached by 13.2% and the maximum percentage increase inCDby 47.6%. Performance degradation in heavy rain at low angles of attack is emulated by an originally creative boundary-layer-tripped technique near the leading edge. Numerical flow visualization technique is used to show premature boundary-layer separation at high angles of attack and the particulate trajectories at various angles of attack. A mathematic model is established to qualitatively study the water film effect on the airfoil geometric changes. All above efforts indicate that two primary mechanisms are accountable for the airfoil aerodynamic penalties. One is to cause premature boundary-layer transition at low AOA and separation at high AOA. The other occurs at times scales consistent with the water film layer, which is thought to alter the airfoil geometry and increase the mass effectively.

Impact of heavy metals on changes in metabolic biomarkers of carp fish, Cirrhinus mrigala

The Indian Major carp fish, Cirrhinus mrigala were exposed to 1/10 th sub lethal concentration of three toxic heavy metals – Cadmium chloride (CdCl 2 ), Lead chloride (PbCl 2 ) and Mercuric Chloride (HgCl 2 ) for a period of 3, 7, 15, 30 and 45 days to study their effect on biochemical and metabolic enzyme biomarkers. The glycogen contents in gill, liver and muscle tissues of carp fish, Cirrhinus mrigala were found to be decreased. The maximum percentage decrease (65.57%) was observed on day 45 in liver tissue under mercuric chloride toxic stress. The succinate dehydrogenase (SDH), malate dehydrogenase (MDA), cytochrome C-oxidase and protein contents in three tissues were gradually decreased, whereas lactate dehydrogenase (LDH), aspartate amino transferase (AAT) and alanine transferase (AIAT) showed a constant and gradual elevation throughout the experimental period of 45 days under the treatment of heavy metals intoxicated fish. It is observed that the increased / decreased percentage was very much pronounced by HgCl 2 ) in liver tissue in particular. These variations have assumed that the fish yields high energy demands to overcome the stress indicated by the existence of hypoproteinamea in all tissues of fish. // //

Exercise-Induced Bronchoconstriction in Children with Asthma: Is There an Association with Urinary Leukotriene E4 or Exhaled Nitric Oxide

Cysteinyl leukotrienes (LT) and airway inflammation are thought to affect exercise-induced bronchoconstriction (EIB). The aim of this study was to investigate the relations between EIB and urinary leukotriene E4 (LTE4) levels and other noninvasive measures of airways inflammation markers in a sample of children with asthma. Pre-exercise urinary LTE4, fractional concentration of exhaled nitric oxide (FeNO) and blood eosinophil count and pulmonary function were measured in 32 children with asthma (mean age±SD, 11.2±2.9 years). Change in forced expiratory volume in one second (FEV1) was determined at 5, 10, and 15 min following 6 min of exercise on a cycle ergometer. Fifteen of the 32 subjects experienced EIB (≥10% decrease in FEV1). The urinary LTE4, FeNO, and blood eosinophil count were significantly related to the maximal percentage decrease in FEV1 after exercise (r=0.44, P<0.05; r=0.36, P<0.05, and r=0.40, P<0.05, respectively). By multiple linear regression, after adjusting for age, gender, and treatment with inhaled corticosteroids, only the pre-exercise urinary LTE4 level was correlated with the maximal percentage decrease in FEV1 after exercise (β=32, P<0.05). Bronchoconstriction after exercise is related to the pre-exercise urinary LTE4 in children with asthma.

Resource and Cost Adjustment in the Design of Allocation Funding Formulas in Public Health Programs

Multiple federal public health programs use funding formulas to allocate funds to states. To characterize the effects of adjusting formula-based allocations for differences among states in the cost of implementing programs, the potential for generating in-state resources, and income disparities, which might be associated with disease risk. Fifty US states and the District of Columbia. Formula-based funding allocations to states for 4 representative federal public health programs were adjusted using indicators of cost (average salaries), potential within-state revenues (per-capita income, the Federal Medical Assistance Percentage, per-capita aggregate home values), and income disparities (Theil index). Percentage of allocation shifted by adjustment, the number of states and the percentage of US population living in states with a more than 20% increase or decrease in funding, maximum percentage increase or decrease in funding. Each adjustor had a comparable impact on allocations across the 4 program allocations examined. Approximately 2% to 8% of total allocations were shifted, with adjustments for variations in income disparity and housing values having the least and greatest effects, respectively. The salary cost and per-capita income adjustors were inversely correlated and had offsetting effects on allocations. With the exception of the housing values adjustment, fewer than 10 states had more than 20% increases or decreases in allocations, and less than 10% of the US population lived in such states. Selection of adjustors for formula-based funding allocations should consider the impacts of different adjustments, correlations between adjustors and other data elements in funding formulas, and the relationship of formula inputs to program objectives.

Combined fluticasone furoate/vilanterol reduces decline in lung function following inhaled allergen 23 h after dosing in adult asthma: a randomised, controlled trial

BackgroundThere is a need for preventative asthma maintenance therapy that provides lasting bronchoprotection against allergen provocation. Fluticasone furoate (FF) is a novel inhaled once-daily corticosteroid, being investigated as monotherapy for asthma and in combination with vilanterol (VI), a novel inhaled once-daily long-acting beta-agonist, for asthma and chronic obstructive pulmonary disease.MethodsIn a crossover study of 52 subjects with mild asthma, FF/VI 100/25mcg and FF 100 dosed once-daily in the evening for 28 days were compared with placebo to evaluate their capacity to provide bronchoprotection against the early asthmatic response (EAR) stimulated by an inhaled allergen challenge. Bronchoprotection was assessed by change from post-saline baseline in weighted mean (wm) forced expiratory volume in 1 s (FEV1) for the first 2 h post-allergen challenge, which was on Day 29 (22–23 h post final dose on Day 28). The EAR was also assessed using maximum percent decrease from post-saline baseline and minimum absolute FEV1; the incidence of adverse events was a secondary endpoint.ResultsFF/VI 100/25 and FF 100 both provided significant bronchoprotection against the EAR for all endpoints assessed. For wmFEV1 over the first 2 h post-allergen challenge, a 162 mL (95% CI, 87 to 237 mL) difference was observed between placebo and FF 100, while a 145 mL (95% CI, 69 to 222 mL) difference was observed between placebo and FF/VI 100/25 treatment. No difference between active treatments was observed (−17 mL; 95% CI, –91 to 57 mL). Both treatments were well tolerated.ConclusionsFF 100 alone and in combination with VI 25 provides significant bronchoprotection against the EAR in subjects with mild asthma. That this protection is provided at the trough of dosing, i.e. 23 h post last dose, supports the utility of FF 100 and FF/VI 100/25 as viable once-daily therapies.Trial registrationClinicaltrials.gov identifier: NCT01128569, GSK Study number: HZA113090

Free Radical Scavenging Activity of Elsholtzia densa

Medicinal plants have been used traditionally to cure a variety of diseases since ancient times. Elsholtzia densa, a rare annual herb of the Kashmir valley, was assessed for its antioxidant efficacy. Antioxidant activity of the crude extracts was evaluated using 1, 1- diphenyl-2-picryl hydrazyl free radical (DPPH), DNA sugar damage, lipid peroxidation, ferric thiocyanate (FTC) and hydrogen peroxide scavenging assays. The maximum percentage decrease of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH) standard solution was recorded for the 50% ethanolic extract (90.48%). The extracts were further evaluated using the thiobarbituric acid reactive substances assay. The methanolic extract showed the highest activity (32.02%) in reducing oxidative damage to DNA. The antioxidant activity of the extracts was also determined using the linoleic acid system and the highest antioxidant activity (49.64%) was found in the 50% ethanolic extract. In the case of the FTC assay, the 50% ethanolic extract showed the highest activity (70.14%) which was comparable to that of α-tocopherol. Moreover, total phenolics concentration was found to be 62.5mg% and 77.5mg% in the cases of absolute ethanolic and 50% ethanolic extracts, respectively. These findings indicate promising antioxidant activity of crude extracts of the plant and the need for further exploration of their effective use in both modern and traditional systems of medicine.

Abstract A6: Association of clinical outcomes and the change in circulating soluble VEGF receptor 2 (VEGFR2) levels in advanced gastric cancer patients treated with telatinib (Tel), capecitabine (X), and cislatin (P).

Abstract Background: Serum VEGFA concentrations and association with metastasic disease/and or poor outcome has been well documented in gastric cancer (GC) patients (pts). However, VEGFA has not been a useful predictor for outcome of treatment with VEGF pathway inhibitors. The soluble form of the VEGF receptor 2 (sVEGFR2) neutralizes circulating VEGF and functions as a negative feedback mechanism to enable partial inhibition of angiogenesis. Reduction in circulating sVEGFR2 levels has been shown upon treatment with multiple small molecule VEGFR inhibitors. Tel is a potent, oral and selective inhibitor of VEGFR 1, 2 and 3 and PDGF receptors. We investigated if marked decrease in the concentration of sVEGFR2 from baseline in response to Tel treatment were associated with lower risk of progression and death compared to pts with smaller decreases or no decrease from baseline. Methods: TEL0805, a phase 2 study, administered Tel with X and P (TEL-XP) as first-line treatment for advanced GC pts. Tel was administered at 900 mg bid beginning day (d)-7 (lead-in for PK/PD analysis) continuously until progression, X was administered d1–14, and P d1 of each 21 day cycle. Serum samples for sVEGR2 analysis were collected on d-7 (baseline) and d1 prior to treatment of the first and every other cycle. Pts whose maximum percentage decrease from baseline was &amp;gt;33% were considered to have “larger” decreases in sVEGFR2. Pts whose maximum percentage decrease from baseline was &amp;lt;33% were considered to have “smaller” decreases, this group included pts with sVEGFR2 levels unchanged or increased from baseline. Results: Twenty-eight pts (25 metastatic, 3 stage III) had sVEGFR2 levels available for analysis. The median baseline sVEGR2 levels were 6,780 pg/mL (range 3,750 to 9,100). Treatment with Tel alone demonstrated onset of reduction of sVEGFR2 by d 7 of the first cycle. Reductions were achieved regardless of tumor histology or disease location. The median of the distribution corresponds to a maximum decrease from baseline of 25%. The duration of OS and PFS were both significantly longer for pts with ≥33% in sVEGFR2 relative to pts with &amp;lt;33%. Median PFS was 4.7 vs. 11.6 months (mths) for pts with smaller versus larger decreases in sVEGFR2 (hazard ratio 0.19; 95% CI: 0.05 to 0.68; p=0.01 by log-rank test). Similarly, median OS was 7.6 mths for pts with smaller decreases in sVEGFR2 and was not reached for pts with larger decreases (hazard ratio 0.23; 95% CI: 0.05 to 1.03; P=0.04 by log-rank test). Follow-up for surviving pts with larger decreases in sVEGFR2 ranges from 9 to 14 mths. Conclusions: In GC pts treated with the TEL-XP regimen, larger percentage decreases in the concentration of sVEGFR2 from baseline were associated with lower risk of progression and death compared to pts with smaller decreases or no decrease from baseline. Further study of sVEGR2 levels as a predictor of response to TEL-XP will be explored in a randomized setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A6.

Effects of intranasal salmeterol and fluticasone given alone and in combination in persistent allergic rhinitis

Backgroundβ2-Agonists have previously been shown to be effective inhibitors of mediator release from airway mucosal mast cells. ObjectiveTo evaluate the effects of intranasal salmeterol and fluticasone propionate alone and in combination on the response to nasal adenosine monophosphate (AMP) challenge to assess mast cell activation. MethodsTwenty-three patients with persistent allergic rhinitis completed a randomized, double-blind, placebo-controlled, 4-way crossover trial. They received once daily treatment with placebo, salmeterol, 50 μg, fluticasone propionate, 500 μg, or fluticasone propionate and salmeterol combination, 500/50 μg, delivered via an antistatic spacer with nasal adapter for 1 week each, with trough measurements being made 12 hours after the first and last dose. The primary outcome was the maximum percentage decrease in peak nasal inspiratory flow after nasal AMP challenge. ResultsFor the primary outcome there was significant protection after single and long-term dosing with fluticasone alone and fluticasone-salmeterol combination, whereas salmeterol alone only afforded protection after the first dose. Fluticasone-salmeterol combination and fluticasone but not salmeterol conferred significant chronic dosing effects on secondary outcomes of nasal symptoms and disease-specific quality of life. There was no potentiation of the response to fluticasone by salmeterol on any outcomes when given in combination. ConclusionChronic dosing with fluticasone but not salmeterol confers anti-inflammatory activity against nasal AMP challenge, but there was no potentiation of fluticasone when given in combination with salmeterol. Thus, salmeterol may not be an effective treatment for use in allergic rhinitis. Trial Registrationclinicaltrials.gov Identifier: NCT01388595.

Asthma diagnosis and treatment: Filling in the information gaps

Current approaches to the diagnosis and management of asthma are based on guideline recommendations, which have provided a framework for the efforts. Asthma, however, is emerging as a heterogeneous disease, and these features need to be considered in both the diagnosis and management of this disease in individual patients. These diverse or phenotypic features add complexity to the diagnosis of asthma, as well as attempts to achieve control with treatment. Although the diagnosis of asthma is often based on clinical information, it is important to pursue objective criteria as well, including an evaluation for reversibility of airflow obstruction and bronchial hyperresponsiveness, an area with new diagnostic approaches. Furthermore, there exist a number of treatment gaps (ie, exacerbations, step-down care, use of antibiotics, and severe disease) in which new direction is needed to improve care. Amajor morbidity in asthmatic patients occurs with exacerbations and in patients with severe disease. Novel approaches to treatment for these conditions will be an important advance to reduce the morbidity associated with asthma.

The Influence of Duration of Fluid Abstinence on Hypotension During Propofol Induction

Prolonged preoperative fasting might be expected to exacerbate hypotension during the induction of general anesthesia. We aimed to establish whether the duration of preoperative abstinence from fluids independently contributed to arterial blood pressure changes and dosage requirements during propofol induction. We prospectively recruited 130 ASA I or II nonhypertensive patients, ages 18 to 65 years scheduled for surgery under general anesthesia. Standard physiological and electroencephalographic bispectral index (BIS) monitoring was applied to each patient. Intravenous propofol infusion was commenced at 40 mg · kg(-1) · h(-1) and reduced to 8 mg · kg(-1) · h(-1) when the BIS decreased to 50. Frequent cardiovascular data were collected for 15 minutes. The primary endpoint was maximal percentage decrease from baseline mean arterial blood pressure (max%ΔMAP). The secondary endpoint was the propofol dose at which BIS decreased to 50 (PDBIS50). Univariate linear regression and then multivariate linear regression was used to analyze the associations between potential predictors, including fasting time, and these 2 endpoints. Mean fluid abstinence time was 694 minutes (range: 115 to 1263 minutes). Unstandardized regression coefficients (95% confidence intervals [CIs]) for fluid abstinence (minutes) versus max%ΔMAP (%) and PDBIS50 (mg) were, respectively, 0.003% (-0.002% to + 0.009%) and 0.021 mg (-0.017 mg to + 0.059 mg). On adjusting for other, significant predictors in a multivariate model and applying type II sum of squares tests, the corresponding values were -0.0001% (-0.004% to + 0.004%, P = 0.94) and -0.006 mg (-0.039 mg to + 0.026 mg, P = 0.70). The effect of a 1-hour increase in fluid abstinence on max%ΔMAP was therefore -0.01% (-0.26% to + 0.24%) and on PDBIS50, -0.38 mg (-2.34 mg to + 1.58 mg). When propofol is infused rapidly for induction of anesthesia in healthy adults younger than 65 years, the duration of preoperative fluid abstinence does not appear to affect MAP or propofol dose requirements.

Urocortin 2 Lowers Blood Pressure and Reduces Plasma Catecholamine Levels in Mice with Hyperadrenergic Activity

Exaggerated adrenergic activity is associated with human hypertension. The peptide urocortin 2 (Ucn 2) inhibits catecholamine synthesis and secretion from adrenal chromaffin cells in vitro and administration to mammals lowers blood pressure (BP). The chromogranin A-null mouse (Chga-/-) manifests systemic hypertension because of excessive catecholamine secretion from the adrenal and decreased catecholamine storage. In the present study, we investigated whether systemic administration of Ucn 2 could reduce BP and adrenal and plasma levels of catecholamines in vivo. Ucn 2 peptide was administered to freely moving, conscious Chga-/- and wild-type control mice. Telemetry and HPLC measured changes in BP and catecholamine levels, respectively. In both groups of mice, Ucn 2 dose-dependently decreased BP, and this effect was mediated by corticotropin factor-receptor type 2. However, in Chga-/- mice, the maximal percentage decrease of systolic BP from basal systolic BP was 37% compared with only a 23% reduction in wild-type mice (P=0.04). In Chga-/- mice only, Ucn 2 decreased adrenal and plasma levels of catecholamines as well as adrenal levels of tyrosine hydroxylase protein and phosphorylation. In vitro mechanistic studies demonstrated that Ucn 2 reduces both catecholamine secretion and tyrosine hydroxylase promoter activity, suggesting that the exaggerated action of Ucn 2 to reduce BP in the Chga-/- mouse is mediated through inhibition of both catecholamine synthesis and secretion. The data suggest that Ucn 2 may be therapeutically useful in regulating the exaggerated sympathoadrenal function of hyperadrenergic hypertension.

TH-D-201B-05: Monte Carlo Simulations of the Effects of Bowtie Filtration on X-Ray Scatter in Cone-Beam CT

Purpose: X‐ray scatter in cone‐beam CT(CBCT) is known to cause image artifacts contrast reduction and CT number inaccuracy. The extent of the effect of x‐ray scatter on CBCTimage quality is determined by the shape and magnitude of the scatter distribution in the projection images. We investigate the effect that bowtie filtration has on the resulting scatter distribution in CBCT.Methods and Materials: A CBCTMonte Carlo(MC) simulation created using an extension of the EGSnrc code is used to evaluate the changes in the scatter distribution of projection images taken with and without bowtie filtration. The bowtie filter is modeled on the F1 bowtie filter used in the Elekta XVI system. The effects of using the bowtie filter is examined for a 16.4 (head) and 30.6 cm (body) water cylinder at four different axis‐to‐detector distances (ADD). The effects of bowtie filtration are also simulated for three views corresponding to rotation angles of 0 45 and 90° of an abdominal scan of a voxelized anthropomorphic phantom. Results: Bowtie filtration caused a maximum percent decrease in the center pixel value of the SPR for the head and body cylinders of 12 and 29 % respectively at an ADD of 56 cm. The percent decrease in the SPR decreased with decreasing ADD reducing to 7 and 19% for the head and body cylinders respectively at an ADD of 18 cm. The percent decrease in the SPR for the three abdominal scan views of 0 45 and 90° when using the bowtie was 28 27 and 18% respectively. Conclusion: The bowtie filter is an effective means of decreasing the magnitude and flattening out the scatter distribution. The bowtie filter is less effective in geometries with small air gaps (decreased ADD) where the magnitude of the scatter is the largest.

Effect of montelukast or salmeterol added to inhaled fluticasone on exercise-induced bronchoconstriction in children

To evaluate the effect of montelukast, 5 mg, or inhaled salmeterol, 50 microg, added to inhaled fluticasone in reducing the maximum percentage decrease in forced expiratory volume in 1 second (FEV1) after a standardized exercise challenge and response to rescue bronchodilation with albuterol in children aged 6 to 14 years with persistent asthma and exercise-induced bronchoconstriction (EIB). Randomized, double-blind, double-dummy, multicenter, 2-period, 4-week, crossover study conducted between December 22, 2005 and November 14, 2008 at 30 centers in Europe, Asia, Mexico, and South America. Patients with asthma receiving inhaled corticosteroids demonstrated an FEV1 of 70% or higher of the predicted value and EIB (defined as a decrease in FEV1 > or = 15% compared with preexercise baseline FEV1 on 2 occasions before randomization). Standardized exercise challenges were performed at baseline (prerandomization) and at the end of each active treatment period. Of 154 patients randomized, 145 completed the study. Montelukast, compared with salmeterol, significantly reduced the mean maximum percentage decrease in FEV1 (10.6% vs 13.8%; P = .009), mean area under the curve for the first 20 minutes after exercise (116.0% x min vs 168.8% x min; P = .006), and median time to recovery (6.0 vs 11.1 minutes; P = .04). Response to albuterol rescue after exercise challenge was significantly greater (P < .001) with montelukast. Montelukast and salmeterol were generally well tolerated. Attenuation and response of EIB to albuterol rescue after exercise challenge were significantly better with montelukast than with salmeterol after 4 weeks of treatment.

Torsional behaviour of rotary NiTi ProTaper Universal instruments after multiple clinical use

To assess the influence of multiple clinical uses on the torsional behaviour of ProTaper Universal rotary NiTi instruments. Root canal treatments were performed on patients using the ProTaper Universal rotary system to prepare canals. Ten sets of instruments were used by an experienced endodontist, each set being used in five molar teeth. After clinical use, S1, S2, F1 and F2 instruments were analysed for damage by optical and scanning electron microscopy. The used sets, along with a control group of 10 sets of new instruments, were then torsion tested based on the ISO 3630-1 specification. Data obtained were subjected to a one-way analysis of variance (anova) with alpha = 0.05. The use of the ProTaper Universal rotary instruments by an experienced endodontist allowed for the cleaning and shaping of the root canal system of five molar teeth without fracture. The maximum torque for instruments S2, F1 and F2, and the angular deflection at fracture for instruments S2 and F1 were significantly lower following clinical use. The largest decrease in maximum torque was 18.6% (P = 0.014) for S2 instruments. The same maximum percent decrease was found for angular deflection at fracture for F1 instruments (P = 0.009). Torsional resistance and angular deflection of used instruments, as compared to that of new instruments, were reduced following clinical use.

Effect of Different Antiasthmatic Treatments on Exercise-Induced Bronchoconstriction in Children With Asthma

Stelmach I, Grzelewski T, Majak P, Jerzynska J, Stelmach W, Kuna P. J Allergy Clin Immunol. 2008;121(2):383–389 PURPOSE OF THE STUDY. To compare the effectiveness of different patterns of antiasthmatic treatments to protect children from exercise-induced bronchospasm (EIB). STUDY POPULATION. This was a randomized, double-blind, placebo-controlled study of 100 children aged 6 to 18 years with atopic asthma sensitive only to house dust mites and EIB. Subjects must have had a resting forced expiratory volume in 1 second (FEV1) of ≥70% predicted and at least a 20% drop in FEV1 after exercise to qualify for the study. METHODS. Participants were randomly assigned to a 4-week double-blind, placebo-controlled trial to receive 1 of the following treatments: (1) budesonide 100 μg + formoterol 4.5 μg twice daily; (2) budesonide 100 μg twice daily + montelukast 5 or 10 mg at bedtime; (3) montelukast 5 or 10 mg at bedtime; (4) budesonide 100 μg twice daily; or (5) placebo alone. All study arms had matching placebo medications from which active drugs were omitted (eg, group 1 had placebo tablets in place of montelukast, etc). At randomization and after 4 weeks on the study medication(s), a treadmill exercise test was performed to evaluate the effectiveness of treatment. RESULTS. Ninety-one subjects with a median age of 11.3 to 12.2 among the groups completed the study. Preexercise FEV1 and EIB, as represented by the area under the curve of time-response curve and by maximum percentage decrease in FEV1 after exercise, did not differ at baseline between the groups. EIB was diminished with all treatments when compared with placebo. The effect of treatment with budesonide plus montelukast and with montelukast alone were greater than budesonide alone or budesonide plus formoterol (P &amp;lt; .001). The budesonide-plus-formoterol group was also better than budesonide alone, but these results did not reach significance (P = .59). CONCLUSIONS. Budesonide plus montelukast or montelukast alone were the most effective treatments for EIB in children. REVIEWER COMMENTS. This was the first study in asthmatic children that evaluated both monotherapy and combination therapy for the reduction of EIB. This study highlights the importance of controller therapy in childhood asthma and the effects on EIB between therapeutic options recommended for childhood asthma. In particular, consideration for the use of montelukast as monotherapy or in combination therapy with inhaled corticosteroids is indicated for EIB in children with similar asthmatic phenotypes.

Investigation of Pulse Transit Time Characteristics During Single and Recurrent Obstructive Respiratory Events

Conventional overnight polysomnography (PSG) used to determine the respiratory behaviour during sleep can be a complex and expensive procedure. Pulse transit time analysis (PTT) has shown potential to detect obstructive apnoeic and hypopnoeic events (OE) in adults. Due to abnormalities in central ventilatory control, recurring OE may occur. This study was undertaken to determine the potential of PTT to differentiate responses during upper airway obstruction in the paediatric population. This preliminary study included 11 children (10 male; aged 7.5 +/- 3.8 year) recruited to investigate PTT trend during single and recurrent OE. PTT measurements were evaluated against the corresponding PSG results pre-scored by two blinded observers. A total of 110 valid OE (47 single and 63 recurrent) were observed during these PSG studies. There were distinct PTT responses observed for these two types of OE with respect to those of tidal breathing (P < 0.05). For the tidal breathing events, the mean absolute standard deviation (SD) and maximal percentage (%) decrease (MAX) were 7.71 ms and 3.88% respectively. For the recurrent OE, the absolute SD, SD (%) and MAX were 52.21 ms, 8.52% and 55.08% accordingly while for the single OE, the absolute SD, SD (%) and MAX were 12.23 ms, 5.27% and 13.56% respectively. The findings herein can suggest that PTT can be a valuable clinical tool in the paediatric respiratory sleep studies.

Tissue zinc levels in precancerous tissue in the gastrointestinal tract of azoxymethane (AOM)-treated rats

Alterations in tissue zinc levels have been documented in patients with gastrointestinal tract malignancies and more frequently, in those with colonic cancer. However, the precise role of tissue zinc in carcinogenesis is not well elucidated. This study, using a well-established colon cancer model in rats, was designed to investigate the relationship of tissue zinc to the carcinogenic process. The aim was to examine tissue zinc levels in the preneoplastic tissues and to study the changes that occur during transition of mucosa from normal to preneoplastic state. Six-week old rats were given a single dose subcutaneous injection of azoxymethane (AOM) (30 mg/kg body weight) and sacrificed after 1, 2, 5, and 9 months of the treatment. Plasma zinc levels showed a significant decrease ( p<0.05) at 9 months compared with controls. Tissue zinc levels showed a significant decrease in the large intestine at 1 and 2 months ( p<0.05) and at 5 and 9 months ( p<0.01), in the small intestine at 2, 5, and 9 months ( p<0.05), and in the stomach at 5 and 9 months ( p<0.05). The maximum percent decrease (45%) in tissue zinc was observed in the large intestine at 9 months. Tissue copper zinc super oxide dismutase (CuZnSOD) activity was assessed in the body of the stomach, small intestine, and large intestine and compared with the control group. There was a significant fall in CuZnSOD levels in the small intestine at 9 months ( p<0.05) and in the large intestine at 5 and 9 months ( p<0.01). Two of these six rats showed histological evidence of precancerous lesions in the mucosa of the colon. This study suggests that the decrease in plasma zinc, tissue zinc and activity of CuZnSOD is associated with development of preneoplastic lesions in the colonic mucosa.

Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies

Increases in T helper (Th) 2 cytokine concentrations have been seen in atopic asthma, with interleukin 4 and interleukin 13 thought to have a role in the physiological response to allergen challenge. Our aim was to assess the therapeutic effect of pitrakinra, an interleukin-4 variant that targets allergic Th2 inflammation by potently inhibiting the binding of interleukin 4 and interleukin 13 to interleukin-4Ralpha receptor complexes. In two independent randomised, double-blind, placebo-controlled, parallel group phase 2a clinical trials, patients with atopic asthma were treated with pitrakinra or placebo via two routes. In study 1, patients were randomly assigned to receive either 25 mg pitrakinra (n=12) or placebo (n=12) by subcutaneous injection once daily. In study 2, patients were randomly assigned to receive either 60 mg pitrakinra (n=16) or placebo (n=16) by nebulisation twice daily. Inhaled allergen challenge was done before and after 4 weeks of treatment. The primary endpoint for study 1 was maximum percentage decrease in forced expiratory volume in 1 s (FEV1) over 4-10 h after allergen challenge, whereas that in study 2 was average percentage decrease in FEV(1) over 4-10 h after allergen challenge. All patients except those with baseline data only were included in our analyses. These trials are registered with ClinicalTrials.gov, numbers NCT00535028 and NCT00535031. No patients dropped out or were lost to follow-up in study 1; in study 2, two patients in the placebo group and one in the pitrakinra group dropped out or were lost to follow-up. These individuals had baseline data only, and were excluded from the analyses. In study 1, there was a 17.1% maximum percentage decrease in FEV1 in the pitrakinra group; by contrast, the maximum decrease was 23.1% in the placebo group (difference 6%, 95% CI -4.37 to 16.32; p=0.243). In study 2, there was a 4.4% average percentage decrease in FEV1 in the pitrakinra group; by contrast, the average percentage decrease was 15.9% in the placebo group (3.7 [95% CI 2.08-6.25] times lower in the pitrakinra group; p=0.0001). There were fewer asthma-related adverse events (p=0.069) and fewer adverse events requiring beta-agonist rescue (p=0.031) after subcutaneous administration of pitrakinra than with placebo. There were too few asthma-related adverse events in study 2 to assess the effect of inhalation of pitrakinra on adverse events. Local treatment, targeted at inhibition of interleukins 4 and 13 in the lung, could substantially diminish the symptoms of asthma.

Toxicity of Organophosphates on Morphology and Locomotor Behavior in Brine Shrimp, Artemia salina

The acute toxicity and hatching success of four organophosphorus insecticides--acephate (ACEP), chlorpyrifos (CPP), monocrotophos (MCP), and profenofos (PF)--was studied in a short-term bioassay using brine shrimp, Artemia salina. Fifty percent hatchability inhibition concentration and median lethal concentration (LC(50)) values were calculated after probit transformation of the resulting data. Among the insecticides tested, CPP is found to be the most toxic and also to inhibit hatching success of A. salina cysts in a concentration-dependent manner. In addition, the effect of these pesticides on locomotor behavior (swimming speed) and morphologic differences were studied in LC(50)-exposed nauplii after 24 hours. The in vivo effect of these insecticides on acetylcholinesterase (Enzyme commission number (EC 3.1.1.7) activity was also determined in LC(50)-exposed nauplii after 24 hours. Maximum percent decrease in their swimming speed and significant morphologic alterations were noticed in CPP-exposed brine shrimps. The order of toxicity was CPP > PF > MCP > ACEP in all the parameters studied.