1,750 research outputs found

    The pharmacokinetics of nebulized nanocrystal budesonide suspension in healthy volunteers.

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    Nanocrystal budesonide (nanobudesonide) is a suspension for nebulization in patients with steroid-responsive pulmonary diseases such as asthma. The pharmacokinetics and safety of the product were compared to those of Pulmicort Respules. Sixteen healthy volunteers were administered nanobudesonide 0.5 and 1.0 mg, Pulmicort Respules 0.5 mg, and placebo in a four-way, randomized crossover design. All nebulized formulations were well tolerated, with no evidence of bronchospasm. Nebulization times were significantly shorter for nanobudesonide compared to Pulmicort Respules. Because of a low oral bioavailability, plasma concentration of budesonide is a good marker of lung-delivered dose. The pharmacokinetics of nanobudesonide 0.5 and 1.0 mg were approximately dose proportional with respect to Cmax, AUC(0-t), and AUC(0-infinity). Nanobudesonide 0.5 mg and Pulmicort Respules 0.5 mg exhibited similar AUCs, suggesting a similar extent of pulmonary absorption. A higher Cmax was noted with nanobudesonide 0.5 mg, and the tmax was significantly different, suggesting a more rapid rate of drug delivery of nanobudesonide 0.5 mg than Pulmicort Respules. In conclusion, nebulized nanobudesonide 0.5 mg was safe in healthy volunteers, with a similar extent of absorption as Pulmicort Respules

    Antimicrobial Susceptibility Testing of Mycobacterium bovis Isolates from Michigan White-Tailed Deer during the 2009 Hunting Season

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    Michigan has had an ongoing outbreak of endemic Mycobacterium bovis which has been recognized within and sustained by its free-ranging white-tailed deer population since 1994. Worldwide, organisms within the Mycobacterium tuberculosis complex have exhibited the ability to develop resistance to antimicrobial agents, resulting in both the multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of human tuberculosis. Michigan's Bovine Tuberculosis Working Group has conducted active antimicrobial susceptibility testing on wildlife isolates of the endemic M. bovis organism at five-year intervals to detect any emerging drug resistance patterns. The results of 33 white-tailed deer origin isolates collected from the 2009 hunting season are reported here. There continues to be no evidence of any drug resistance except for pyrazinamide resistance. These results are likely due to the lack of antibacterial treatment applied to either wildlife or domestic animals which would provide selection pressure for the development of drug resistance

    Recent Decisions

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    Comments on recent decisions by Robert E. Veverka, John W. Dell, James A. Wysocki, Theodore A. Fitzgerald, Robert W. Cox, Philip B. Byrne, Thomas R. Joyce, and Cornelius Collins

    Development and preliminary testing of the psychosocial adjustment to hereditary diseases scale

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    Background: The presence of Lynch syndrome (LS) can bring a lifetime of uncertainty to an entire family as members adjust to living with a high lifetime cancer risk. The research base on how individuals and families adjust to genetic-linked diseases following predictive genetic testing has increased our understanding of short-term impacts but gaps continue to exist in knowledge of important factors that facilitate or impede long-term adjustment. The failure of existing scales to detect psychosocial adjustment challenges in this population has led researchers to question the adequate sensitivity of these instruments. Furthermore, we have limited insight into the role of the family in promoting adjustment. Methods: The purpose of this study was to develop and initially validate the Psychosocial Adjustment to Hereditary Diseases (PAHD) scale. This scale consists of two subscales, the Burden of Knowing (BK) and Family Connectedness (FC). Items for the two subscales were generated from a qualitative data base and tested in a sample of 243 participants from families with LS. Results: The Multitrait/Multi-Item Analysis Program-Revised (MAP-R) was used to evaluate the psychometric properties of the PAHD. The findings support the convergent and discriminant validity of the subscales. Construct validity was confirmed by factor analysis and Cronbach’s alpha supported a strong internal consistency for BK (0.83) and FC (0.84). Conclusion: Preliminary testing suggests that the PAHD is a psychometrically sound scale capable of assessing psychosocial adjustment. We conclude that the PAHD may be a valuable monitoring tool to identify individuals and families who may require therapeutic interventions

    Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model

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    peer-reviewedThe aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~109microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~109 L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.The authors and their work were supported by the APC Microbiome Institute. The APC Microbiome Institute is funded by Science Foundation Ireland (SFI). This publication has emanated from research supported by a research grant from Science Foundation Ireland (SFI) under Grant Number SFI/12/RC/2273

    Test-retest reliability of TRIMP in collegiate ice hockey players

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    The utility of the heart rate derived variable TRaining IMPulse (TRIMP) for assessing internal training load in ice hockey players is not clear. Having a reliable measure of internal training load during on-ice training sessions would help coaches program exercise training. This study determined the reliability of TRIMP during on-ice training sessions in ice hockey players. Twelve Division I collegiate male ice hockey players (aged 18–23 years) had their heart rate (HR) data recorded during two on-ice practice sessions separated by two weeks. TRIMP and other descriptive HR variables were compared between sessions. TRIMP demonstrated moderate reliability during on-ice sessions. Systematic error, quantified as standardized change in means was negligible (–0.19); random error quantified as the percent typical error (%TE) was moderate (12.2%); and, test-retest correlation was very strong (0.75). TRIMP is suitable for quantifying training load during intermittent work in hockey athletes. The results from our study can be used to determine the threshold for meaningful change in TRIMP, which may aid in informing decisions by coaches and strength training staff regarding on-ice training session difficulty and composition

    Modeling of Water Injection into a Vacuum

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    A loosely coupled two-phase vacuum water plume model has been developed. This model consists of a source flow model to describe the expansion of water vapor, and the Lagrangian equations of motion for particle trajectories. Gas/Particle interaction is modeled through the drag force induced by the relative velocities. Particles are assumed traveling along streamlines. The equations of motion are integrated to obtain particle velocity along the streamline. This model has been used to predict the mass flux in a 5 meter radius hemispherical domain resulting from the burst of a water jet of 1.5 mm in diameter, mass flow rate of 24.2 g/s, and stagnation pressure of 21.0 psia, which is the nominal Orbiter water dump condition. The result is compared with an empirical water plume model deduced from a video image of the STS-29 water dump. To further improve the model, work has begun to numerically simulate the bubble formation and bursting present in a liquid stream injected into a vacuum. The technique of smoothed particle hydrodynamics was used to formulate this simulation. A status and results of the on-going effort are presented and compared to results from the literature

    Heatwaves and mortality in Queensland 2010–2019: implications for a homogenous state-wide approach

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    Heatwaves are a significant cause of adverse health outcomes and mortality in Australia, worsening with climate change. In Queensland, the northeastern-most state, little is known about the impact of heatwaves outside of the capital city of Brisbane. This study aims to explore the impact of heatwaves on mortality across various demographic and environmental conditions within Queensland from 2010 to 2019. The Excess Heat Factor was used to indicate heatwave periods at the Statistical Area 2 (SA2) level. Registered deaths data from the Australian Bureau of Statistics and heatwave data from the Bureau of Meteorology were matched using a case-crossover approach. Relative risk and 95% confidence intervals were calculated across years, regions, age, sex, rurality, socioeconomic status, and cause of death. Heatwaves were associated with a 5% increase in all-cause mortality compared to deaths on non-heatwave days, with variability across the state. The risk of death on a heatwave day versus a non-heatwave day varied by heatwave severity. Individuals living in urban centers, the elderly, and those living in regions of lower socioeconomic status were most impacted by heatwave mortality. The relative risk of dying from neoplasms, nervous system conditions, respiratory conditions, and mental and behavioral conditions increased during heatwaves. As heatwaves increase in Queensland due to climate change, understanding the impact of heatwaves on mortality across Queensland is important to tailor public health messages. There is considerable variability across communities, demographic groups, and medical conditions, and as such messages need to be tailored to risk
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