Special report on the data collection programs for the ground based nitrogen washout experiment. Volume 1: User's guide

NASA Technical Reports Server (NTRS)

Bueker, P. A.

1982-01-01

The Nitrogen Washout System measures nitrogen elimination on a breath basis from the body tissues of a subject breathing pure oxygen. The system serves as a prototype for a Space Shuttle Life Sciences experiment and in the Environmental Physiology Laboratory. Typically, a subject washes out body nitrogen for three hours while breathing oxygen from a mask enclosed in a positive-pressure oxygen tent. A nitrogen washout requires one test operator and the test subject. A DEC LSI-11/02 computer is used to (1) control and calibrate the mass spectrometer and Skylab spirometer, (2) gather and store experimental data and (3) provide limited real time analysis and more extensive post-experiment analysis. Five programs are used to gather and store the experimental data and perform all the real time control and analysis.

Enhanced washout of 99mTc-tetrofosmin in hypertrophic cardiomyopathy: quantitative comparisons with regional 123I-BMIPP uptake and wall thickness determined by MRI.

PubMed

Thet-Thet-Lwin; Takeda, Tohoru; Wu, Jin; Fumikura, Yuko; Iida, Keiji; Kawano, Satoru; Yamaguchi, Iwao; Itai, Yuji

2003-07-01

The diagnostic value of technetium-99m tetrofosmin (TF) washout in hypertrophic cardiomyopathy (HCM) was examined by investigating its relation to the metabolic abnormality depicted by iodine-123 beta-methyl- p-iodophenylpentadecanoic acid (BMIPP) uptake and the left ventricular (LV) myocardial wall thickness as measured by magnetic resonance imaging (MRI). TF washout was evaluated in 31 patients with HCM and 23 normal control subjects using 30-min (early) and 3-h (delayed) TF single-photon emission tomography images. The LV myocardial wall was divided into 19 segments and the percentage TF washout, regional BMIPP uptake and LV wall thickness were measured in each segment. Mean TF washout in the patients with HCM was significantly faster than that in normal control subjects (23.7+/-5.7 vs 13.4+/-4.1, P<0.0001). In the patients with HCM, TF washout showed an excellent correlation with MRI wall thickness ( r=0.82, P<0.0001) and a good inverse correlation with regional BMIPP uptake ( r=-0.72, P<0.0001). In addition, a good linear correlation was observed between TF uptake and MRI wall thickness in the 19 regional segments. In conclusion, the degree of TF washout corresponds well with the severity of myocardial wall thickness and the degree of metabolic abnormality in patients with HCM. These results suggest that enhanced TF washout might provide additional clinical information regarding metabolic alterations in HCM.

Hepatocellular carcinoma in cirrhotic patients at multidetector CT: hepatic venous phase versus delayed phase for the detection of tumour washout

PubMed Central

Furlan, A; Marin, D; Vanzulli, A; Patera, G Palermo; Ronzoni, A; Midiri, M; Bazzocchi, M; Lagalla, R; Brancatelli, G

2011-01-01

Objectives Our aim was to compare retrospectively hepatic venous and delayed phase images for the detection of tumour washout during multiphasic multidetector row CT (MDCT) of the liver in patients with hepatocellular carcinoma (HCC). Methods 30 cirrhotic patients underwent multiphasic MDCT in the 90 days before liver transplantation. MDCT was performed before contrast medium administration and during hepatic arterial hepatic venous and delayed phases, images were obtained at 12, 55 and 120 s after trigger threshold. Two radiologists qualitatively evaluated images for lesion attenuation. Tumour washout was evaluated subjectively and objectively. Tumour-to-liver contrast (TLC) was measured for all pathologically proven HCCs. Results 48 HCCs were detected at MDCT. 46 of the 48 tumours (96%) appeared as either hyper- or isoattenuating during the hepatic arterial phase subjective washout was present in 15 HCCs (33%) during the hepatic venous phase and in 35 (76%) during the delayed phase (p<0.001, McNemar’s test). Objective washout was present in 30 of the 46 HCCs (65%) during the hepatic venous phase and in 42 of the HCCs (91%) during the delayed phase (p=0.001). The delayed phase yielded significantly higher mean TLC absolute values compared with the hepatic venous phase (−16.1±10.8 HU vs −10.5±10.2 HU; p<0.001). Conclusions The delayed phase is superior to the hepatic venous phase for detection of tumour washout of pathologically proven HCC in cirrhotic patients. PMID:21081569

Wash-out in N{sub 2}-dominated leptogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hahn-Woernle, F., E-mail: fhahnwo@mppmu.mpg.de

2010-08-01

We study the wash-out of a cosmological baryon asymmetry produced via leptogenesis by subsequent interactions. Therefore we focus on a scenario in which a lepton asymmetry is established in the out-of-equilibrium decays of the next-to-lightest right-handed neutrino. We apply the full classical Boltzmann equations without the assumption of kinetic equilibrium and including all quantum statistical factors to calculate the wash-out of the lepton asymmetry by interactions of the lightest right-handed state. We include scattering processes with top quarks in our analysis. This is of particular interest since the wash-out is enhanced by scatterings and the use of mode equations withmore » quantum statistical distribution functions. In this way we provide a restriction on the parameter space for this scenario.« less

Penile blood flow by xenon-133 washout

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haden, H.T.; Katz, P.G.; Mulligan, T.

1989-06-01

Penile erectile failure is often attributed to abnormalities of vascular supply or drainage, but few direct measurements of penile blood flow have been made. We describe the xenon washout method for measurement of penile blood flow, and present the results obtained in a group of normal and impotent subjects. The procedure was performed with standard nuclear imaging equipment. Flaccid-state penile blood flow in the impotent patients studied was not significantly different from the normal group, suggesting that flaccid-state measurements may not be helpful in evaluation of erectile failure. However, this method can be used to measure penile venous outflow withmore » stimulated or induced erection, and may provide a method for detecting abnormal venous leakage.« less

Ventilatory inhomogeneity determined from multiple-breath washouts during sustained microgravity on Spacelab SLS-1.

PubMed

Prisk, G K; Guy, H J; Elliott, A R; Paiva, M; West, J B

1995-02-01

We used multiple-breath N2 washouts (MBNW) to study the inhomogeneity of ventilation in four normal humans (mean age 42.5 yr) before, during, and after 9 days of exposure to microgravity on Spacelab Life Sciences-1. Subjects performed 20-breath MBNW at tidal volumes of approximately 700 ml and 12-breath MBNW at tidal volumes of approximately 1,250 ml. Six indexes of ventilatory inhomogeneity were derived from data from 1) distribution of specific ventilation (SV) from mixed-expired and 2) end-tidal N2, 3) change of slope of N2 washout (semilog plot) with time, 4) change of slope of normalized phase III of successive breaths, 5) anatomic dead space, and 6) Bohr dead space. Significant ventilatory inhomogeneity was seen in the standing position at normal gravity (1 G). When we compared standing 1 G with microgravity, the distributions of SV became slightly narrower, but the difference was not significant. Also, there were no significant changes in the change of slope of the N2 washout, change of normalized phase III slopes, or the anatomic and Bohr dead spaces. By contrast, transition from the standing to supine position in 1 G resulted in significantly broader distributions of SV (P < 0.05) and significantly greater changes in the changes in slope of the N2 washouts (P < 0.001), indicating more ventilatory inhomogeneity in that posture. Thus these techniques can detect relatively small changes in ventilatory inhomogeneity. We conclude that the primary determinants of ventilatory inhomogeneity during tidal breathing in the upright posture are not gravitational in origin.

Ventilatory inhomogeneity determined from multiple-breath washouts during sustained microgravity on Spacelab SLS-1

NASA Technical Reports Server (NTRS)

Prisk, G. Kim; Guy, Harold J. B.; Elliott, Ann R.; Paiva, Manuel; West, John B.

1995-01-01

We used multiple-breath N2 washouts (MBNW) to study the homogeneity of ventilation in four normal humans (mean age 42.5 yr) before, during, and after 9 days of exposure to microgravity on Spacelab Life Sciences-1. Subjects performed 20-breath MBNW at tidal volumes of approximately 700 ml and 12-breath MBNW at tidal volumes of approximately 1,250 ml. Six indexes of ventilatory inhomogeneity were derived from data from (1) distribution of specific ventilation (SV) from mixed-expired and (2) end-tidal N2, (3) change of slope of N2 washout (semilog plot) with time, (4) change of slope of normalized phase III of successive breaths, (5) anatomic lead dead space, and (6) Bohr dead space. Significant ventilatory inhomogeneity was seen in the standing position at normal gravity (1 G). When we compared standing 1 G with microgravity, the distributions of SV became slightly narrower, but the difference was not significant. Also, there were no significant changes in the change of slope of the N2 washout, change of normalized phase III slopes, or the anatomic and Bohr dead spaces. By contrast, transition from the standing to supine position in 1 G resulted in significantly broader distributions of SV and significantly greater changes in the changes in slope of the N2 washouts, indicating more ventilatory inhomogeneity in that posture. Thus these techniques can detect relatively small changes in ventilatory inhomogeneity. We conclude that the primary determinants of ventilatory inhomogeneity during tidal breathing in the upright posture are not gravitational in origin.

Determination of washout performance of various monochrome displays under simulated flight ambient and solar lighting conditions

NASA Technical Reports Server (NTRS)

Batson, Vernon M.; Robertson, James B.; Parrish, Russell V.

1990-01-01

The aircraft cockpit ambient lighting simulation system (ACALSS) has been developed to study display readability and associated pilot/vehicle performance effects in a part-task simulator cockpit. In the study reported here, the ACALSS was used to determine the illumination levels at which subjects lose the ability to maintain aircraft states when using three display technologies as display media for primary flight displays: a standard monochrome EL (electroluminescent) flat-panel, a laboratory-class monochrome CRT, and an enhanced-brightness EL flat-panel. The multivariate statistical technique of modified profile analysis was used to test for performance differences between display devices as functions of illumination levels. The standard monochrome EL flat-panel display began to washout after the 2500 foot-candle level of illumination. The monochrome CRT began to washout after the 5500 foot-candle level of illumination. No performance decrements by increased illumination up to the 12,000 foot-candle level were found for the enhanced-brightness EL flat-panel display. What was not anticipated was that half the subjects would subjectively prefer the CRT over the enhanced-brightness EL, even though their performance errors would have indicated the opposite.

Roll tracking effects of G-vector tilt and various types of motion washout

NASA Technical Reports Server (NTRS)

Jex, H. R.; Magdaleno, R. E.; Junker, A. M.

1978-01-01

In a dogfight scenario, the task was to follow the target's roll angle while suppressing gust disturbances. All subjects adopted the same behavioral strategies in following the target while suppressing the gusts, and the MFP-fitted math model response was generally within one data symbol width. The results include the following: (1) comparisons of full roll motion (both with and without the spurious gravity tilt cue) with the static case. These motion cues help suppress disturbances with little net effect on the visual performance. Tilt cues were clearly used by the pilots but gave only small improvement in tracking errors. (2) The optimum washout (in terms of performance close to real world, similar behavioral parameters, significant motion attenuation (60 percent), and acceptable motion fidelity) was the combined attenuation and first-order washout. (3) Various trends in parameters across the motion conditions were apparent, and are discussed with respect to a comprehensive model for predicting adaptation to various roll motion cues.

Continuous distributions of specific ventilation recovered from inert gas washout

NASA Technical Reports Server (NTRS)

Lewis, S. M.; Evans, J. W.; Jalowayski, A. A.

1978-01-01

A new technique is described for recovering continuous distributions of ventilation as a function of tidal ventilation/volume ratio from the nitrogen washout. The analysis yields a continuous distribution of ventilation as a function of tidal ventilation/volume ratio represented as fractional ventilations of 50 compartments plus dead space. The procedure was verified by recovering known distributions from data to which noise had been added. Using an apparatus to control the subject's tidal volume and FRC, mixed expired N2 data gave the following results: (a) the distributions of young, normal subjects were narrow and unimodal; (b) those of subjects over age 40 were broader with more poorly ventilated units; (c) patients with pulmonary disease of all descriptions showed enlarged dead space; (d) patients with cystic fibrosis showed multimodal distributions with the bulk of the ventilation going to overventilated units; and (e) patients with obstructive lung disease fell into several classes, three of which are illustrated.

Emptying patterns of the lung studied by multiple-breath N2 washout

NASA Technical Reports Server (NTRS)

Lewis, S. M.

1978-01-01

Changes in the nitrogen concentration seen during the single-breath nitrogen washout reflect changes in relative flow (ventilation) from units with differing ventilation/volume ratios. The multiple-breath washout provides sufficient data on ventilation for units with varying ventilation/volume ratios to be plotted as a function of the volume expired. Flow from the dead space may also be determined. In young normals the emptying patterns are narrow and unimodal throughout the alveolar plateau with little or no flow from the dead space at the end of the breath. Older normals show more flow from the dead space, particularly toward the end of the breath, and some show a high ventilation/volume ratio mode early in the breath. Patients with obstructive lung disease have a high flow from the dead space which is present throughout the breath. A well ventilated mode at the end of the breath is seen in some obstructed subjects. Patients with cystic fibrosis showed a poorly ventilated mode appearing at the end of the breath as well as a very high dead space.

Risk Assessment for the Explosive Washout Lagoons (Site 4), Umatilla Depot Activity Hermiston, Oregon

DTIC Science & Technology

1992-03-01

Activity .............................. 2 2-2 Explosive Washout Lagoons (Site 4) and Washout Plant Area ............................... 2-3 3-1 Site 4...ponds for liquid wastes from bomb-washing operations in the washout plant . The measured dimensions of the flat bottoms of the two lagoons are 30 by 80...explosives washout plant system was drained, flushed, and cleaned approximately once each week from the mid-1950s until 1965. The lagoons received all of the

Washout policies in long-term indwelling urinary catheterization in adults: a short version cochrane review.

PubMed

Sinclair, Lesley; Hagen, Suzanne; Cross, Stephen

2011-09-01

People requiring long-term bladder draining with an indwelling catheter can experience catheter blockage. Regimens involving different solutions can be used to wash out catheters with the aim of preventing blockage. To determine if certain washout regimens (including no washout) are better than others in terms of effectiveness, acceptability, complications, quality of life, and economics for the management of long-term indwelling urinary catheters in adults. We searched the Cochrane Incontinence Group Specialized Trials Register (searched April 30, 2009), MEDLINE (January 1966 to April 2009), MEDLINE In-Process (April 30, 2009), EMBASE (January 1980 to April 2009), and CINAHL (December 1981 to April 2009). Additionally, we examined all reference lists of identified trials and contacted manufacturers and researchers in the field. All randomized and quasi-randomized trials comparing catheter washout policies (e.g., washout vs. no washout, different washout solutions, frequency, duration, volume, concentration, method of administration) in adults (16 years and above) in any setting (i.e., hospital, nursing/residential home, community) with an indwelling urethral or suprapubic catheter in place for more than 28 days. Data were extracted by three reviewers independently and compared. Disagreements were resolved by discussion. Data were processed as described in the Cochrane Handbook. If the trial data were not fully reported, clarification was sought from the authors. For categorical outcomes, the numbers reporting an outcome were related to the numbers at risk in each group to derive a risk ratio (RR). For continuous outcomes, means, and standard deviations were used to derive weighted mean differences (WMD). No meta-analysis of study results was possible. Five trials met the inclusion criteria involving 242 patients (132 completed) in two cross-over and three parallel-group randomized controlled trials. Only three of the eight comparisons pre-stated in the review

A six-month prospective evaluation of personality traits, psychiatric symptoms and quality of life in ayahuasca-naïve subjects.

PubMed

Barbosa, Paulo Cesar Ribeiro; Cazorla, Irene Maurício; Giglio, Joel Sales; Strassman, Rick

2009-09-01

The authors assessed 23 subjects immediately before and six months (27.5 weeks) after their first ayahuasca experience in an urban Brazilian religious setting, either Santo Daime (N = 15) or União do Vegetal (N = 8). Measures included scores on instruments assessing psychiatric symptoms, personality variables and quality of life. Independent variables were the frequency of ayahuasca use throughout the period and the length of ayahuasca wash-out after six months. Santo Daime subjects had a significant reduction of minor psychiatric symptoms, improvement of mental health, and a change in attitude towards more confidence and optimism. The União do Vegetal group had a significant decrease in physical pain, and attitude change towards more independence. Independence was positively correlated with the frequency of ayahuasca use and negatively correlated with the wash-out period. We discuss possible mechanisms by which these changes may occur and suggest areas for future research.

Measurement of lung volume in mechanically ventilated monkeys with an ultrasonic flow meter and the nitrogen washout method.

PubMed

Schibler, Andreas; Hammer, Jürg; Isler, Ruedi; Buess, Christian; Newth, Christopher J L

2004-01-01

Measurement of functional residual capacity (FRC) during mechanical ventilation is important to standardise respiratory system compliance and adjust the ventilator settings to optimise lung recruitment. In the present study we compared three methods to measure FRC. The bias flow nitrogen washout technique (FRC(N2MC)), the multiple breath nitrogen washout (FRC(MBNW)) and the multiple breath sulphur-hexafluoride washout using the molar mass signal of an ultrasonic flow meter (FRC(MBSF6)) were compared in six adult monkeys after endotracheal intubation and during spontaneous breathing and mechanical ventilation at three different positive end-expiratory pressure (PEEP) levels of 0, 5 and 10 cmH2O. Animal research laboratory. We found good agreement between all three methods and they all accurately measured changes in FRC when PEEP was increased. The coefficients of variance of the three measurement techniques were in the same range (1.3-9.2%). The measurement of the tracer gas concentration with the molar mass signal of the ultrasonic flow meter provides a good and simple alternative to respiratory mass spectrometer for FRC measurements in ventilated subjects.

CO2 Washout Testing of the REI and EM-ACES Space Suits

NASA Technical Reports Server (NTRS)

Mitchell, Kathryn C.; Norcross, Jason

2012-01-01

When a space suit is used during ground testing, adequate carbon dioxide (CO2) washout must be provided for the suited subject. Symptoms of acute CO2 exposure depend on partial pressure of CO2 (ppCO2), metabolic rate of the subject, and other factors. This test was done to characterize inspired oronasal ppCO2 in the Rear Entry I-Suit (REI) and the Enhanced Mobility Advanced Crew Escape Suit (EM-ACES) for a range of workloads and flow rates for which ground testing is nominally performed. Three subjects were tested in each suit. In all but one case, each subject performed the test twice. Suit pressure was maintained at 4.3 psid. Subjects wore the suit while resting, performing arm ergometry, and walking on a treadmill to generate metabolic workloads of about 500 to 3000 BTU/hr. Supply airflow was varied between 6, 5, and 4 actual cubic feet per minute (ACFM) at each workload. Subjects wore an oronasal mask with an open port in front of the mouth and were allowed to breathe freely. Oronasal ppCO2 was monitored in real time by gas analyzers with sampling tubes connected to the mask. Metabolic rate was calculated from the total CO2 production measured by an additional gas analyzer at the suit air outlet. Real-time metabolic rate was used to adjust the arm ergometer or treadmill workload to meet target metabolic rates. In both suits, inspired CO2 was affected mainly by the metabolic rate of the subject: increased metabolic rate significantly (P < 0.05) increased inspired ppCO2. Decreased air flow caused small increases in inspired ppCO2. The effect of flow was more evident at metabolic rates . 2000 BTU/hr. CO2 washout values of the EM-ACES were slightly but not significantly better than those of the REI suit. Regression equations were developed for each suit to predict the mean inspired ppCO2 as a function of metabolic rate and suit flow rate. This paper provides detailed descriptions of the test hardware, methodology, and results as well as implications for future

A New Surgical Device for Anterograde Intraoperative Rectal Washout.

PubMed

Rondelli, Fabio; Santinelli, Roberto; Stella, Paolo; Bugiantella, Walter; Ceccarelli, Graziano; Balzarotti, Ruben Carlo; De Rosa, Michele; Avenia, Nicola

2018-06-01

Colorectal cancer is the fourth most diffuse cause of death in the world and local recurrence is associated with a reduced long-term life expectancy, with a reduced quality of life. Rectal washout at the anastomosis site leads to a statistically significant reduction of local recurrences. We developed the idea of a new laparoscopic stapler with an integrated washout system that could decontaminate the rectal stump before resection, without the need to enlarge the standard surgical incision or even to distort the incision site, closing the rectal stump just below the inferior part of the cancer, and then proceeding with the resection and stapling of the distal part of the tumor. Combined with these canonical functionalities, the new device, equipped with a patented washout system (patent number EP 3103401A1) will also allow to inject in the closed bowel a physiologic saline liquid. In force of the mechanical action of the liquid injected, carcinogenic exfoliated cells eventually floating in the affected region of the colonic lumen will be expelled through the anal orifice. The intraoperative rectal washout, both in minimally invasive and in traditional open surgery, thus becomes a simple, effective, and reproducible procedure. We describe the technical features and the possible clinical applications of a potentially new surgical laparoscopic stapler coupled with an integrated irrigation system. We have patented the system and we are developing a prototype with the aim to start an experimental pilot study.

Burr Hole Washout versus Craniotomy for Chronic Subdural Hematoma: Patient Outcome and Cost Analysis

PubMed Central

Regan, Jacqueline M.; Worley, Emmagene; Shelburne, Christopher; Pullarkat, Ranjit; Watson, Joseph C.

2015-01-01

Chronic subdural hematomas (CSDH), which are frequently encountered in neurosurgical practice, are, in the majority of cases, ideally treated with surgical drainage. Despite this common practice, there is still controversy surrounding the best surgical procedure. With lack of clear evidence of a superior technique, surgeons are free to base the decision on other factors that are not related to patient care. A retrospective chart review of 119 patients requiring surgical drainage of CSDH was conducted at a large tertiary care center over a three-year period. Of the cases reviewed, 58 patients underwent craniotomy, while 61 patients underwent burr hole washout. The study focused on re-operation rates, mortality, and morbidity, as measured by Glasgow coma scores (GCS), discharge Rankin disability scores, and discharge disposition. Secondary endpoints included length of stay and cost of procedure. Burr hole washout was superior to craniotomy with respect to patient outcome, length of stay and recurrence rates. In both study groups, patients required additional surgical procedures (6.6% of burr hole patients and 24.1% of craniotomy patients) (P = 0.0156). Of the patients treated with craniotomy, 51.7% were discharged home, whereas 65.6% of the burr hole patients were discharged home. Patients who underwent burr hole washout spent a mean of 78.8 minutes in the operating suite while the patients undergoing craniotomy spent 129.4 minutes (P < 0.001). The difference in mean cost per patient, based solely on operating time, was $2,828 (P < 0.001). This does not include the further cost due to additional procedures and hospital stay. The mean length of stay after surgical intervention was 3 days longer for the craniotomy group (P = 0.0465). Based on this retrospective study, burr hole washout is superior for both patients’ clinical and financial outcome; however, prospective long-term multicenter clinical studies are required to verify these findings. PMID:25611468

Burr hole washout versus craniotomy for chronic subdural hematoma: patient outcome and cost analysis.

PubMed

Regan, Jacqueline M; Worley, Emmagene; Shelburne, Christopher; Pullarkat, Ranjit; Watson, Joseph C

2015-01-01

Chronic subdural hematomas (CSDH), which are frequently encountered in neurosurgical practice, are, in the majority of cases, ideally treated with surgical drainage. Despite this common practice, there is still controversy surrounding the best surgical procedure. With lack of clear evidence of a superior technique, surgeons are free to base the decision on other factors that are not related to patient care. A retrospective chart review of 119 patients requiring surgical drainage of CSDH was conducted at a large tertiary care center over a three-year period. Of the cases reviewed, 58 patients underwent craniotomy, while 61 patients underwent burr hole washout. The study focused on re-operation rates, mortality, and morbidity, as measured by Glasgow coma scores (GCS), discharge Rankin disability scores, and discharge disposition. Secondary endpoints included length of stay and cost of procedure. Burr hole washout was superior to craniotomy with respect to patient outcome, length of stay and recurrence rates. In both study groups, patients required additional surgical procedures (6.6% of burr hole patients and 24.1% of craniotomy patients) (P = 0.0156). Of the patients treated with craniotomy, 51.7% were discharged home, whereas 65.6% of the burr hole patients were discharged home. Patients who underwent burr hole washout spent a mean of 78.8 minutes in the operating suite while the patients undergoing craniotomy spent 129.4 minutes (P < 0.001). The difference in mean cost per patient, based solely on operating time, was $2,828 (P < 0.001). This does not include the further cost due to additional procedures and hospital stay. The mean length of stay after surgical intervention was 3 days longer for the craniotomy group (P = 0.0465). Based on this retrospective study, burr hole washout is superior for both patients' clinical and financial outcome; however, prospective long-term multicenter clinical studies are required to verify these findings.

Evaluation of the Appropriate Washout Period Following Fan Therapy for Dyspnea in Patients With Advanced Cancer: A Pilot Study.

PubMed

Kako, Jun; Morita, Tatsuya; Yamaguchi, Takuhiro; Sekimoto, Asuko; Kobayashi, Masamitsu; Kinoshita, Hiroya; Ogawa, Asao; Zenda, Sadamoto; Uchitomi, Yosuke; Inoguchi, Hironobu; Matsushima, Eisuke

2018-02-01

To clarify the duration required for dyspnea to return to baseline severity after fan therapy, to evaluate whether fan-to-legs therapy or no fan therapy would be a suitable control therapy, and to investigate changes in patients' face surface temperature after fan therapy. In this pilot study, all participants received 3 interventions in the following order: no fan, fan to legs, and fan to face. Participants used a fan for 5 minutes, and they scored their dyspnea at 10-minute intervals for 60 minutes or until the score had returned to its baseline value, whichever occurred first. Nine patients with advanced cancer admitted to a palliative care unit were included; they had dyspnea at rest and rated its severity as at least 3 points on a 0- to 10-point numerical rating scale. Descriptive statistics and the Wilcoxon signed rank test were used to analyze the data. All patients completed the study. Of the 9 participants, 6 experienced a clinical benefit from using a fan to their faces. Of these patients, only 2 participants' (2 of 6) dyspnea scores returned to baseline by the end of the 60-minute assessment period after exposure to fan-to-face therapy. In fan-to-legs and no fan settings, there was no change in the dyspnea scores. There were significant differences between the baseline face surface temperature and that after fan-to-face and fan-to-legs settings. When using a crossover design to investigate the effect of fan therapy on dyspnea, 1 hour is an insufficient washout period.

CO2 Washout Testing Using Various Inlet Vent Configurations in the Mark-III Space Suit

NASA Technical Reports Server (NTRS)

Korona, F. Adam; Norcross, Jason; Conger, Bruce; Navarro, Moses

2014-01-01

Requirements for using a space suit during ground testing include providing adequate carbon dioxide (CO2) washout for the suited subject. Acute CO2 exposure can lead to symptoms including headache, dyspnea, lethargy and eventually unconsciousness or even death. Symptoms depend on several factors including inspired partial pressure of CO2 (ppCO2), duration of exposure, metabolic rate of the subject and physiological differences between subjects. Computational Fluid Dynamic (CFD) analysis has predicted that the configuration of the suit inlet vent has a significant effect on oronasal CO2 concentrations. The main objective of this test is to characterize inspired oronasal ppCO2 for a variety of inlet vent configurations in the Mark-III space suit across a range of workload and flow rates. As a secondary objective, results will be compared to the predicted CO2 concentrations and used to refine existing CFD models. These CFD models will then be used to help design an inlet vent configuration for the Z-2 space suit, which maximizes oronasal CO2 washout. This test has not been completed, but is planned for January 2014. The results of this test will be incorporated into this paper. The testing methodology used in this test builds upon past CO2 washout testing performed on the Z-1 suit, Rear Entry I-Suit (REI) and the Enhanced Mobility Advanced Crew Escape Suit (EM-ACES). Three subjects will be tested in the Mark-III space suit with each subject performing two test sessions to allow for comparison between tests. Six different helmet inlet vent configurations will be evaluated during each test session. Suit pressure will be maintained at 4.3 psid. Subjects will wear the suit while walking on a treadmill to generate metabolic workloads of approximately 2000 and 3000 BTU/hr. Supply airflow rates of 6 and 4 actual cubic feet per minute (ACFM) will be tested at each workload. Subjects will wear an oronasal mask with an open port in front of the mouth and will be allowed to

Washout of ⁸²Rb as a marker of impaired tissue integrity, obtained by list-mode cardiac PET/CT: relationship with perfusion/metabolism patterns of myocardial viability.

PubMed

Chien, David T; Bravo, Paco; Higuchi, Takahiro; Merrill, Jennifer; Bengel, Frank M

2011-08-01

Myocardial washout of the potassium analogue (82)Rb may indicate tissue impairment. Few studies have evaluated its usefulness for viability assessment, and controversial results were reported. We revisited this topic using list-mode positron emission tomography (PET)/CT. A total of 22 patients with chronic ischemic cardiomyopathy (ICM) and 11 control subjects with normal CT coronary angiogram were studied. Rest (82)Rb PET/CT studies were acquired in list mode and resampled to static, gated, and dynamic images. Using a 17-segment model, (82)Rb washout was determined by monoexponential fitting of myocardial time-activity curves. In ICM patients, (18)F-fluorodeoxyglucose (FDG) studies were obtained in the same session and segments were classified as normally perfused, mismatch, or matched defect. (82)Rb washout was minimal and homogeneous in control subjects. Normally perfused segments of ICM did not differ (p = 0.33). ICM patients had a left ventricular ejection fraction (LVEF) of 25 ± 12%, 25/353 mismatched, and 46/353 matched defect segments. (82)Rb washout was higher in hypoperfused vs normal segments (p < 0.05), but not different between mismatch and matched defect (p = 0.18). Intraindividual analysis in nine patients showing both FDG mismatch and matched defect confirmed absence of differences. Overall, segmental (82)Rb washout correlated inversely with (82)Rb uptake (r = -0.70; p < 0.05) and less well with FDG uptake (r = -0.31; p < 0.05). Using state-of-the-art PET/CT technology for myocardial viability assessment, (82)Rb washout does not distinguish between perfusion/metabolism patterns of hibernating myocardium and scar. Tissue integrity may be at least partially impaired in hibernation.

CO2 Washout Testing of the REI and EM-ACES Space Suits

NASA Technical Reports Server (NTRS)

Mitchell, Kate; Norcross, Jason

2011-01-01

Requirements for using a space suit during ground testing include providing adequate carbon dioxide (CO2) washout for the suited subject. Acute CO2 exposure can lead to symptoms including headache, dyspnea, lethargy and eventually unconsciousness or even death. Symptoms depend on several factors including partial pressure of CO2 (ppCO2), duration of exposure, metabolic rate of the subject and physiological differences between subjects. The objective of this test was to characterize inspired oronasal ppCO2 in the Rear Entry I-Suit (REI) and the Enhanced Mobility Advanced Crew Escape Suit (EM-ACES) across a range of workloads and flow rates for which ground testing is nominally performed. Three subjects were tested in each suit. In all but one case, each subject performed the test twice to allow for comparison between tests. Suit pressure was maintained at 4.3 psid. Subjects wore the suit while resting, performing arm ergometry, and walking on a treadmill to generate metabolic workloads of approximately 500 to 3000 BTU/hr. Supply airflow was varied at 6, 5 and 4 actual cubic feet per minute (ACFM) at each workload. Subjects wore an oronasal mask with an open port in front of the mouth and were allowed to breathe freely. Oronasal ppCO2 was monitored real-time via gas analyzers with sampling tubes connected to the oronasal mask. Metabolic rate was calculated from the total CO2 production measured by an additional gas analyzer at the air outlet from the suit. Real-time metabolic rate was used to adjust the arm ergometer or treadmill workload to meet target metabolic rates. In both suits, inspired CO2 was primarily affected by the metabolic rate of the subject, with increased metabolic rate resulting in increased inspired ppCO2. Suit flow rate also affected inspired ppCO2, with decreased flow causing small increases in inspired ppCO2. The effect of flow was more evident at metabolic rates greater than or equal to 2000 BTU/hr. Results were consistent between suits, with

Krogh-cylinder and infinite-domain models for washout of an inert diffusible solute from tissue.

PubMed

Secomb, Timothy W

2015-01-01

Models based on the Krogh-cylinder concept are developed to analyze the washout from tissue by blood flow of an inert diffusible solute that permeates blood vessel walls. During the late phase of washout, the outflowing solute concentration decays exponentially with time. This washout decay rate is predicted for a range of conditions. A single capillary is assumed to lie on the axis of a cylindrical tissue region. In the classic "Krogh-cylinder" approach, a no-flux boundary condition is applied on the outside of the cylinder. An alternative "infinite-domain" approach is proposed that allows for solute exchange across the boundary, but with zero net exchange. Both models are analyzed, using finite-element and analytical methods. The washout decay rate depends on blood flow rate, tissue diffusivity and vessel permeability of solute, and assumed boundary conditions. At low blood flow rates, the washout rate can exceed the value for a single well-mixed compartment. The infinite-domain approach predicts slower washout decay rates than the Krogh-cylinder approach. The infinite-domain approach overcomes a significant limitation of the Krogh-cylinder approach, while retaining its simplicity. It provides a basis for developing methods to deduce transport properties of inert solutes from observations of washout decay rates. © 2014 John Wiley & Sons Ltd.

Altered metabolism of orally administered loxoprofen in human subjects after an oral administration of loxoprofen for three consecutive days followed by a seven-day washout.

PubMed

Kim, In-Wha; Chung, Suk-Jae; Shim, Chang-Koo

2002-04-01

The effect of pretreatment (i.e., oral administration of loxoprofen for 3 consecutive days followed by a 7-day washout) on the pharmacokinetics and metabolism of the drug was studied in humans. In a control study, a Loxonin tablet (60 mg as loxoprofen anhydrous) was administered orally to 6 healthy male Korean subjects. In a pretreatment study, a Loxonin tablet was administered orally to the subjects once daily for 3 consecutive days. On the 10(th) day, a Loxonin tablet was administered orally to the subjects, and the concentrations of loxoprofen and the trans- and cis-alcohol metabolites in the plasma and urine were measured as a function of time. Using this pretreatment, the area under the curve (AUC) of the trans-alcohol metabolite of loxoprofen in the plasma, but not those of loxoprofen and the cis-alcohol metabolite, was increased (1.5-fold, p < 0.05), leading to increased contribution of the trans-alcohol metabolite to the total urinary recovery of loxoprofen (1.3-fold, p < 0.05). The urinary recovery of total metabolites, which was largely (> 90%) comprised of conjugate metabolites, was also increased as a result of the pretreatment (1.5-fold, p < 0.05). These results indicate that stereoselective reduction to trans-alcohol metabolites as well as the phase II metabolism of loxoprofen may be increased by such a pretreatment in human subjects. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:973-979, 2002

Uricosuric effect of Roselle (Hibiscus sabdariffa) in normal and renal-stone former subjects.

PubMed

Prasongwatana, Vitoon; Woottisin, Surachet; Sriboonlue, Pote; Kukongviriyapan, Veerapol

2008-05-22

The Roselle (Hibiscus sabdariffa) was investigated for its uricosuric effect. A human model with nine subjects with no history of renal stones (non-renal stone, NS) and nine with a history of renal stones (RS) was used in this study. A cup of tea made from 1.5 g of dry Roselle calyces was provided to subjects twice daily (morning and evening) for 15 days. A clotted blood and two consecutive 24-h urine samples were collected from each subject three times: (1) at baseline (control); (2) on days 14 and 15 during the tea drinking period; and (3) 15 days after the tea drinking was stopped (washout). Serum and 24-h urinary samples were analyzed for uric acid and other chemical compositions related to urinary stone risk factors. All analyzed serum parameters were within normal ranges and similar; between the two groups of subjects and among the three periods. Vis-à-vis the urinary parameters, most of the baseline values for both groups were similar. After taking the tea, the trend was an increase in oxalate and citrate in both groups and uric acid excretion and clearance in the NS group. In the RS group, both uric acid excretion and clearance were significantly increased (p<0.01). When the fractional excretion of uric acid (FEUa) was calculated, the values were clearly increased in both the NS and SF groups after the intake of tea and returned to baseline values in the washout period. These changes were more clearly observed when the data for each subject was presented individually. Our data demonstrate a uricosuric effect of Roselle calyces. Since the various chemical constituents in Roselle calyces have been identified, the one(s) exerting this uricosuric effect need to be identified.

The washout of combustion-generated hydrogen chloride. [rocket exhaust raindrop scavenging quantification

NASA Technical Reports Server (NTRS)

Fenton, D. L.; Purcell, R. Y.; Hrdina, D.; Knutson, E. O.

1980-01-01

The coefficient for the washout from a rocket exhaust cloud of HCl generated by the combustion of an ammonium perchlorate-based solid rocket propellant such as that to be used for the Space Shuttle Booster is determined. A mathematical model of HCl scavenging by rain is developed taking into account rain droplet size, fall velocity and concentration under various rain conditions, partitioning of exhaust HCl between liquid and gaseous phases, the tendency of HCl to promote water vapor condensation and the concentration and size of droplets within the exhaust cloud. The washout coefficient is calculated as a function of total cloud water content, total HCl content at 100% relative humidity, condensation nuclei concentration and rain intensity. The model predictions are compared with experimental results obtained in scavenging tests with solid rocket exhaust and raindrops of different sizes, and the large reduction in washout coefficient at high relative humidities predicted by the model is not observed. A washout coefficient equal to 0.0000512 times the -0.176 power of the mass concentration of HCl times the 0.773 power of the rainfall intensity is obtained from the experimental data.

Preschool Multiple-Breath Washout Testing. An Official American Thoracic Society Technical Statement.

PubMed

Robinson, Paul D; Latzin, Philipp; Ramsey, Kathryn A; Stanojevic, Sanja; Aurora, Paul; Davis, Stephanie D; Gappa, Monika; Hall, Graham L; Horsley, Alex; Jensen, Renee; Lum, Sooky; Milla, Carlos; Nielsen, Kim G; Pittman, Jessica E; Rosenfeld, Margaret; Singer, Florian; Subbarao, Padmaja; Gustafsson, Per M; Ratjen, Felix

2018-03-01

Obstructive airway disease is nonuniformly distributed throughout the bronchial tree, although the extent to which this occurs can vary among conditions. The multiple-breath washout (MBW) test offers important insights into pediatric lung disease, not available through spirometry or resistance measurements. The European Respiratory Society/American Thoracic Society inert gas washout consensus statement led to the emergence of validated commercial equipment for the age group 6 years and above; specific recommendations for preschool children were beyond the scope of the document. Subsequently, the focus has shifted to MBW applications within preschool subjects (aged 2-6 yr), where a "window of opportunity" exists for early diagnosis of obstructive lung disease and intervention. This preschool-specific technical standards document was developed by an international group of experts, with expertise in both custom-built and commercial MBW equipment. A comprehensive review of published evidence was performed. Recommendations were devised across areas that place specific age-related demands on MBW systems. Citing evidence where available in the literature, recommendations are made regarding procedures that should be used to achieve robust MBW results in the preschool age range. The present work also highlights the important unanswered questions that need to be addressed in future work. Consensus recommendations are outlined to direct interested groups of manufacturers, researchers, and clinicians in preschool device design, test performance, and data analysis for the MBW technique.

Early surgical suction and washout for treatment of cytotoxic drug extravasations.

PubMed

Vandeweyer, E; Deraemaecker, R

2000-02-01

This case report is presented to assess safety and efficiency of early suction and saline washout of extravasated cytotoxic drugs. Through multiple small skin incisions, the area of extravasation is first suctioned and subsequently extensively washed out with saline. Incisions are left open and the arm is elevated for 24 hours. A complete healing was obtained in five days without any skin or soft tissue loss. No additional treatment was needed. Early referral and surgical treatment by suction and washout is a safe and reliable treatment protocol for major cytotoxic drug extravasation injuries.

Washout of hepatocellular carcinoma on portal venous phase of multidetector computed tomography in a pre-transplant population.

PubMed

Kitzing, Yu Xuan; Ng, Bernard H K; Kitzing, Bjoern; Waugh, Richard; Kench, James G; Strasser, Simone I; McCormack, Samuel

2015-12-01

Washout is an important diagnostic imaging feature of hepatocellular carcinoma (HCC) on computed tomography (CT). The primary aim of this study is to evaluate the prevalence and the interobserver variation in the detection of portal venous phase (PVP) washout of HCCs using CT in a transplant population. The secondary aim is to evaluate factors influencing the detection of PVP washout. Forty-five patients who underwent CT liver imaging within the 60 days before transplantation had viable HCCs confirmed on pathology. Two radiologists retrospectively reviewed the images for HCCs including features of arterial enhancement and PVP washout. Clinical data, peak kilovoltage, imaging features of portal hypertension, region of interest attenuation measurements of the individual lesions, background liver parenchyma and portal vein were obtained. Liver to lesion attenuation ratio was also calculated. Statistical analysis was performed. The two readers identified 50 arterially enhancing HCCs in 45 patients. In consensus, the two readers identified washout in 60% of the HCCs with a substantial interobserver agreement (kappa = 0.633). PVP washout was associated with larger lesion size, increased background liver parenchyma attenuation, increased liver to lesion attenuation ratio, increased portal vein attenuation and hepatitis B viral status (P = 0.027, 0.008, 0.014, 0.017 and 0.037 respectively). In our transplant population, portal venous phase washout was seen in 60% of the hypervascular HCCs. Factors influencing the presence of PVP washout include lesion size as well as the liver and portal vein attenuation reflective of the portal haemodynamics. © 2015 The Royal Australian and New Zealand College of Radiologists.

Gravitational independence of single-breath washout tests in recumbent dogs

NASA Technical Reports Server (NTRS)

Tomioka, Shinichi; Kubo, Susumu; Guy, Harold J. B.; Prisk, G. K.

1988-01-01

The effect of gravitational orientation in the mechanism of lung filling and emptying in dogs was examined by conducting simultaneously Ar-bolus and N2 single-breath washout tests (SBWTs) in 10 anesthetized dogs (prone and supine), with three of the dogs subjected to body rotation. Transpulmonary pressure was measured simultaneously, allowing identification of the lung volume above residual volume at which there was an inflection point in the pressure-volume curve. Combined resident gas and bolus SBWTs in recumbent dogs were found to be different from such tests in humans; in dogs, the regional distribution of ventilation was not primarily determined by gravity. The measurements did not make it possible to discern exact mechanisms of filling and emptying, but both processes appear to be related to lung, thorax, and mediastinum interactions and/or differences in regional mechanical properties of the lungs.

Evaluation of the Impact of Alveolar Nitrogen Excretion on Indices Derived from Multiple Breath Nitrogen Washout

PubMed Central

Nielsen, Niklas; Nielsen, Jorgen G.; Horsley, Alex R.

2013-01-01

Background A large body of evidence has now accumulated describing the advantages of multiple breath washout tests over conventional spirometry in cystic fibrosis (CF). Although the majority of studies have used exogenous sulphur hexafluoride (SF6) as the tracer gas this has also led to an increased interest in nitrogen washout tests, despite the differences between these methods. The impact of body nitrogen excreted across the alveoli has previously been ignored. Methods A two-compartment lung model was developed that included ventilation heterogeneity and dead space (DS) effects, but also incorporated experimental data on nitrogen excretion. The model was used to assess the impact of nitrogen excretion on washout progress and accuracy of functional residual capacity (FRC) and lung clearance index (LCI) measurements. Results Excreted nitrogen had a small effect on accuracy of FRC (1.8%) in the healthy adult model. The error in LCI calculated with true FRC was greater (6.3%), and excreted nitrogen contributed 21% of the total nitrogen concentration at the end of the washout. Increasing DS and ventilation heterogeneity both caused further increase in measurement error. LCI was increased by 6–13% in a CF child model, and excreted nitrogen increased the end of washout nitrogen concentration by 24–49%. Conclusions Excreted nitrogen appears to have complex but clinically significant effects on washout progress, particularly in the presence of abnormal gas mixing. This may explain much of the previously described differences in washout outcomes between SF6 and nitrogen. PMID:24039916

Can the Contrast-Enhanced Ultrasound Washout Rate Be Used to Predict Microvascular Invasion in Hepatocellular Carcinoma?

PubMed

Zhu, Wei; Qing, Xiachuan; Yan, Feng; Luo, Yan; Li, Yongzhong; Zhou, Xiang

2017-08-01

The objective of this study was to investigate use of the washout rate of hepatocellular carcinoma on contrast-enhanced ultrasound (CEUS) for pre-operative determination of the presence of microvascular invasion. The study included 271 patients who underwent liver resection for hepatocellular carcinoma between April 2008 and December 2012, and were examined with contrast-enhanced ultrasound before surgery. Patients were followed up at 3-mo intervals for 3 y. Four washout patterns were classified according to the start time of washout: rapid, portal, delayed and slow. Rapid washout, presence of two or more tumors and tumor size ≥5 cm were identified as independent pre-operative predictors of microvascular invasion on multivariate analysis. Recurrence rates for patients with none, one, two or three predictors were 22.6%, 34.7%, 57.6% and 75.0%, respectively. In combination with tumor number and tumor size, contrast-enhanced ultrasound washout rate may have a role in identifying hepatocellular carcinoma patients with microvascular invasion. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Washout Ratio in the Hepatic Vein Measured by Contrast-Enhanced Ultrasonography to Distinguish Between Inflammatory and Noninflammatory Hepatic Disorders in Dogs.

PubMed

Morishita, K; Hiramoto, A; Michishita, A; Takagi, S; Osuga, T; Lim, S Y; Nakamura, K; Sasaki, N; Ohta, H; Takiguchi, M

2017-05-01

Perflubutane microbubbles, a second-generation ultrasound contrast agent, are phagocytized by Kupffer cells. This characteristic may be useful to differentiate diffuse hepatic diseases in dogs. To determine whether the washout ratio in the hepatic vein (HV) measured by contrast-enhanced ultrasonography (CEUS) can distinguish between inflammatory and noninflammatory hepatic disorders in dogs. Forty-one client-owned dogs with hepatic disorders including 14 with hepatitis, 7 with primary hypoplasia of the portal vein (PHPV), 9 with congenital portosystemic shunt (cPSS), and 11 with other hepatopathy were enrolled. Six dogs without hepatic disease also were evaluated as healthy controls. Dogs with hepatic disorders were prospectively included. Contrast-enhanced ultrasonography of the HV was performed for 2 minutes. Washout ratio was defined as the attenuation rate from peak intensity to the intensity at the end of the CEUS study. Washout ratio in the hepatitis group (median, 18.0%; range, 2.0-37.0%) was significantly lower than that of the PHPV (median, 52.2%; range, 11.5-86.3%), cPSS (median, 60.0%; range, 28.6-77.4%), other hepatopathy (median, 70.5%; range, 26.6-88.4%), and normal (median, 78.0%; range, 60.7-91.7%) groups. The area under the receiver operating characteristic curve for hepatitis was 0.960, with a 95% confidence interval (CI) of 0.853-0.990. Washout ratio ≤37.1% resulted in a sensitivity of 100% (95% CI, 78.5-100%) and specificity of 85.2% (95% CI, 67.5-94.1%) for the prediction of hepatitis. Washout ratio can distinguish hepatitis from the other noninflammatory disorders with high accuracy. This result might reflect impaired Kupffer cell phagocytosis in dogs with hepatitis. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

CO2 Washout Testing Using Various Inlet Vent Configurations in the Mark-III Space Suit

NASA Technical Reports Server (NTRS)

Korona, F. Adam; Norcross, Jason; Conger, Bruce; Navarro, Moses

2014-01-01

Requirements for using a space suit during ground testing include providing adequate carbon dioxide (CO2) washout for the suited subject. Acute CO2 exposure can lead to symptoms including headache, dyspnea, lethargy and eventually unconsciousness or even death. Symptoms depend on several factors including inspired partial pressure of CO2 (ppCO2), duration of exposure, metabolic rate of the subject and physiological differences between subjects. Computational Fluid Dynamic (CFD) analysis has predicted that the configuration of the suit inlet vent has a significant effect on oronasal CO2 concentrations. The main objective of this test was to characterize inspired oronasal ppCO2 for a variety of inlet vent configurations in the Mark-III suit across a range of workload and flow rates. Data and trends observed during testing along with refined CFD models will be used to help design an inlet vent configuration for the Z-2 space suit. The testing methodology used in this test builds upon past CO2 washout testing performed on the Z-1 suit, Rear Entry I-Suit (REI) and the Enhanced Mobility Advanced Crew Escape Suit (EM-ACES). Three subjects performed two test sessions each in the Mark-III suit to allow for comparison between tests. Six different helmet inlet vent configurations were evaluated during each test session. Suit pressure was maintained at 4.3 psid. Suited test subjects walked on a treadmill to generate metabolic workloads of approximately 2000 and 3000 BTU/hr. Supply airflow rates of 6 and 4 actual cubic feet per minute (ACFM) were tested at each workload. Subjects wore an oronasal mask with an open port in front of the mouth and were allowed to breathe freely. Oronasal ppCO2 was monitored real-time via gas analyzers with sampling tubes connected to the oronasal mask. Metabolic rate was calculated from the total oxygen consumption and CO2 production measured by additional gas analyzers at the air outlet from the suit. Realtime metabolic rate measurements were

Carbon Dioxide Washout Testing Using Various Inlet Vent Configurations in the Mark-III Space Suit

NASA Technical Reports Server (NTRS)

Korona, F. Adam; Norcross, Jason; Conger, Bruce; Navarro, Moses

2014-01-01

Requirements for using a space suit during ground testing include providing adequate carbon dioxide (CO2) washout for the suited subject. Acute CO2 exposure can lead to symptoms including headache, dyspnea, lethargy, and eventually unconsciousness or even death. Symptoms depend on several factors including inspired partial pressure of CO2 (ppCO2), duration of exposure, metabolic rate of the subject, and physiological differences between subjects. Computational Fluid Dynamics (CFD) analysis has predicted that the configuration of the suit inlet vent has a significant effect on oronasal CO2 concentrations. The main objective of this test was to characterize inspired oronasal ppCO2 for a variety of inlet vent configurations in the Mark-III suit across a range of workload and flow rates. Data and trends observed during testing along with refined CFD models will be used to help design an inlet vent configuration for the Z-2 space suit. The testing methodology used in this test builds upon past CO2 washout testing performed on the Z-1 suit, Rear Entry I-Suit, and the Enhanced Mobility Advanced Crew Escape Suit. Three subjects performed two test sessions each in the Mark-III suit to allow for comparison between tests. Six different helmet inlet vent configurations were evaluated during each test session. Suit pressure was maintained at 4.3 psid. Suited test subjects walked on a treadmill to generate metabolic workloads of approximately 2000 and 3000 BTU/hr. Supply airflow rates of 6 and 4 actual cubic feet per minute were tested at each workload. Subjects wore an oronasal mask with an open port in front of the mouth and were allowed to breathe freely. Oronasal ppCO2 was monitored real-time via gas analyzers with sampling tubes connected to the oronasal mask. Metabolic rate was calculated from the CO2 production measured by an additional gas analyzer at the air outlet from the suit. Real-time metabolic rate measurements were used to adjust the treadmill workload to meet

CO2 Washout Testing Using Various Inlet Vent Configurations in the Mark-III Space Suit

NASA Technical Reports Server (NTRS)

Korona, F. Adam; Norcross, Jason; Conger, Bruce; Navarro, Moses

2014-01-01

Requirements for using a space suit during ground testing include providing adequate carbon dioxide (CO2) washout for the suited subject. Acute CO2 exposure can lead to symptoms including headache, dyspnea, lethargy and eventually unconsciousness or even death. Symptoms depend on several factors including inspired partial pressure of CO2 (ppCO2), duration of exposure, metabolic rate of the subject and physiological differences between subjects. Computational Fluid Dynamic (CFD) analysis has predicted that the configuration of the suit inlet vent has a significant effect on oronasal CO2 concentrations. The main objective of this test was to characterize inspired oronasal ppCO2 for a variety of inlet vent configurations in the Mark-III suit across a range of workload and flow rates. Data and trends observed during testing along with refined CFD models will be used to help design an inlet vent configuration for the Z-2 space suit. The testing methodology used in this test builds upon past CO2 washout testing performed on the Z-1 suit, Rear Entry I-Suit (REI) and the Enhanced Mobility Advanced Crew Escape Suit (EM-ACES). Three subjects performed two test sessions each in the Mark-III suit to allow for comparison between tests. Six different helmet inlet vent configurations were evaluated during each test session. Suit pressure was maintained at 4.3 psid. Suited test subjects walked on a treadmill to generate metabolic workloads of approximately 2000 and 3000 BTU/hr. Supply airflow rates of 6 and 4 actual cubic feet per minute (ACFM) were tested at each workload. Subjects wore an oronasal mask with an open port in front of the mouth and were allowed to breathe freely. Oronasal ppCO2 was monitored real-time via gas analyzers with sampling tubes connected to the oronasal mask. Metabolic rate was calculated from the total oxygen consumption and CO2 production measured by additional gas analyzers at the air outlet from the suit. Real-time metabolic rate measurements were

Analytical evaluation of two motion washout techniques

NASA Technical Reports Server (NTRS)

Young, L. R.

1977-01-01

Practical tools were developed which extend the state of the art of moving base flight simulation for research and training purposes. The use of visual and vestibular cues to minimize the actual motion of the simulator itself was a primary consideration. The investigation consisted of optimum programming of motion cues based on a physiological model of the vestibular system to yield 'ideal washout logic' for any given simulator constraints.

Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder.

PubMed

Correll, Christoph U; Josiassen, Richard C; Liang, Grace S; Burke, Joshua; O'Brien, Christopher F

2017-08-01

Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with mood disorder or schizophrenia/schizoaffective disorder (SCHZ, presented separately) who received up to 48 weeks of treatment. KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers); 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1-7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline); and CGI-TD responders (subjects with score ≤2 ["much improved" or "very much improved"]). Treatment effect sizes (Cohen's d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. Efficacy analyses were conducted in 77 subjects (DBPC) and 73 subjects (VE) with a mood disorder. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -3.6, d = 0.94; 40 mg, -2.4, d = 0.55; PBO, -0.7). AIMS mean score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -5.8; 40 mg, -4.2). By Week 52 (end of washout), AIMS mean scores in both dose groups were returning toward baseline levels, indicating re-emergence of TD. CGI-TD scores showed a similar pattern: Week 6 (80 mg, 2.7, d = 0.64; 40 mg, 2.9, d = 0.39; PBO, 3.2), Week 48

Bacterial Selection during the Formation of Early-Stage Aerobic Granules in Wastewater Treatment Systems Operated Under Wash-Out Dynamics

PubMed Central

Weissbrodt, David G.; Lochmatter, Samuel; Ebrahimi, Sirous; Rossi, Pierre; Maillard, Julien; Holliger, Christof

2012-01-01

Aerobic granular sludge is attractive for high-rate biological wastewater treatment. Biomass wash-out conditions stimulate the formation of aerobic granules. Deteriorated performances in biomass settling and nutrient removal during start-up have however often been reported. The effect of wash-out dynamics was investigated on bacterial selection, biomass settling behavior, and metabolic activities during the formation of early-stage granules from activated sludge of two wastewater treatment plants (WWTP) over start-up periods of maximum 60 days. Five bubble-column sequencing batch reactors were operated with feast-famine regimes consisting of rapid pulse or slow anaerobic feeding followed by aerobic starvation. Slow-settling fluffy granules were formed when an insufficient superficial air velocity (SAV; 1.8 cm s−1) was applied, when the inoculation sludge was taken from a WWTP removing organic matter only, or when reactors were operated at 30°C. Fast-settling dense granules were obtained with 4.0 cm s−1 SAV, or when the inoculation sludge was taken from a WWTP removing all nutrients biologically. However, only carbon was aerobically removed during start-up. Fluffy granules and dense granules were displaying distinct predominant phylotypes, namely filamentous Burkholderiales affiliates and Zoogloea relatives, respectively. The latter were predominant in dense granules independently from the feeding regime. A combination of insufficient solid retention time and of leakage of acetate into the aeration phase during intensive biomass wash-out was the cause for the proliferation of Zoogloea spp. in dense granules, and for the deterioration of BNR performances. It is however not certain that Zoogloea-like organisms are essential in granule formation. Optimal operation conditions should be elucidated for maintaining a balance between organisms with granulation propensity and nutrient removing organisms in order to form granules with BNR activities in short

Bacterial Selection during the Formation of Early-Stage Aerobic Granules in Wastewater Treatment Systems Operated Under Wash-Out Dynamics.

PubMed

Weissbrodt, David G; Lochmatter, Samuel; Ebrahimi, Sirous; Rossi, Pierre; Maillard, Julien; Holliger, Christof

2012-01-01

Aerobic granular sludge is attractive for high-rate biological wastewater treatment. Biomass wash-out conditions stimulate the formation of aerobic granules. Deteriorated performances in biomass settling and nutrient removal during start-up have however often been reported. The effect of wash-out dynamics was investigated on bacterial selection, biomass settling behavior, and metabolic activities during the formation of early-stage granules from activated sludge of two wastewater treatment plants (WWTP) over start-up periods of maximum 60 days. Five bubble-column sequencing batch reactors were operated with feast-famine regimes consisting of rapid pulse or slow anaerobic feeding followed by aerobic starvation. Slow-settling fluffy granules were formed when an insufficient superficial air velocity (SAV; 1.8 cm s(-1)) was applied, when the inoculation sludge was taken from a WWTP removing organic matter only, or when reactors were operated at 30°C. Fast-settling dense granules were obtained with 4.0 cm s(-1) SAV, or when the inoculation sludge was taken from a WWTP removing all nutrients biologically. However, only carbon was aerobically removed during start-up. Fluffy granules and dense granules were displaying distinct predominant phylotypes, namely filamentous Burkholderiales affiliates and Zoogloea relatives, respectively. The latter were predominant in dense granules independently from the feeding regime. A combination of insufficient solid retention time and of leakage of acetate into the aeration phase during intensive biomass wash-out was the cause for the proliferation of Zoogloea spp. in dense granules, and for the deterioration of BNR performances. It is however not certain that Zoogloea-like organisms are essential in granule formation. Optimal operation conditions should be elucidated for maintaining a balance between organisms with granulation propensity and nutrient removing organisms in order to form granules with BNR activities in short

Anticontrol of Hopf bifurcation and control of chaos for a finance system through washout filters with time delay.

PubMed

Zhao, Huitao; Lu, Mengxia; Zuo, Junmei

2014-01-01

A controlled model for a financial system through washout-filter-aided dynamical feedback control laws is developed, the problem of anticontrol of Hopf bifurcation from the steady state is studied, and the existence, stability, and direction of bifurcated periodic solutions are discussed in detail. The obtained results show that the delay on price index has great influences on the financial system, which can be applied to suppress or avoid the chaos phenomenon appearing in the financial system.

Comparison of flow and gas washout characteristics between pressure control and high-frequency percussive ventilation using a test lung

PubMed Central

Dutta, Rabijit; Xing, Tao; Swanson, Craig; Heltborg, Jeff; Murdoch, Gordon K

2018-01-01

Objective A comparison between flow and gas washout data for high-frequency percussive ventilation (HFPV) and pressure control ventilation (PCV) under similar conditions is currently not available. This bench study aims to compare and describe the flow and gas washout behavior of HFPV and PCV in a newly designed experimental setup and establish a framework for future clinical and animal studies. Approach We studied gas washout behavior using a newly designed experimental setup that is motivated by the multi-breath nitrogen washout measurements. In this procedure, a test lung was filled with nitrogen gas before it was connected to a ventilator. Pressure, volume, and oxygen concentrations were recorded under different compliance and resistance conditions. PCV was compared with two settings of HFPV, namely, HFPV-High and HFPV-Low, to simulate the different variations in its clinical application. In the HFPV-Low mode, the peak pressures and drive pressures of HFPV and PCV are matched, whereas in the HFPV-High mode, the mean airway pressures (MAP) are matched. Main results HFPV-Low mode delivers smaller tidal volume (VT) as compared to PCV under all lung conditions, whereas HFPV-High delivers a larger VT. HFPV-High provides rapid washout as compared to PCV under all lung conditions. HFPV-Low takes a longer time to wash out nitrogen except at a low compliance, where it expedites washout at a smaller VT and MAP compared to PCV washout. Significance Various flow parameters for HFPV and PCV are mathematically defined. A shorter washout time at a small VT in low compliant test lungs for HFPV could be regarded as a hypothesis for lung protective ventilation for animal or human lungs. PMID:29369819

Comparison of flow and gas washout characteristics between pressure control and high-frequency percussive ventilation using a test lung.

PubMed

Dutta, Rabijit; Xing, Tao; Swanson, Craig; Heltborg, Jeff; Murdoch, Gordon K

2018-03-15

A comparison between flow and gas washout data for high-frequency percussive ventilation (HFPV) and pressure control ventilation (PCV) under similar conditions is currently not available. This bench study aims to compare and describe the flow and gas washout behavior of HFPV and PCV in a newly designed experimental setup and establish a framework for future clinical and animal studies. We studied gas washout behavior using a newly designed experimental setup that is motivated by the multi-breath nitrogen washout measurements. In this procedure, a test lung was filled with nitrogen gas before it was connected to a ventilator. Pressure, volume, and oxygen concentrations were recorded under different compliance and resistance conditions. PCV was compared with two settings of HFPV, namely, HFPV-High and HFPV-Low, to simulate the different variations in its clinical application. In the HFPV-Low mode, the peak pressures and drive pressures of HFPV and PCV are matched, whereas in the HFPV-High mode, the mean airway pressures (MAP) are matched. HFPV-Low mode delivers smaller tidal volume (V T ) as compared to PCV under all lung conditions, whereas HFPV-High delivers a larger V T . HFPV-High provides rapid washout as compared to PCV under all lung conditions. HFPV-Low takes a longer time to wash out nitrogen except at a low compliance, where it expedites washout at a smaller V T and MAP compared to PCV washout. Various flow parameters for HFPV and PCV are mathematically defined. A shorter washout time at a small V T in low compliant test lungs for HFPV could be regarded as a hypothesis for lung protective ventilation for animal or human lungs.

Analytic model for washout of HCl(g) from dispersing rocket exhaust clouds

NASA Technical Reports Server (NTRS)

Pellett, G. L.

1981-01-01

The potential is investigated that precipitation scavenging of HCl from large solid rocket exhaust clouds may result in unacceptably acidic rain in the Cape Canaveral, Florida, area before atmospheric dispersion reduces HCl concentrations to safe limits. Several analytic expressions for HCl(g) and HCl(g + aq) washout are derived; a geometric mean washout coefficient is recommended. A previous HCl washout model is refined and applied to a space shuttle case (70 t HCl exhausted up to 4 km) and eight Titan 3 (60 percent less exhaust) dispersion cases. The vertical column density (sigma) decays were deduced by application of a multilayer Gaussian diffusion model to seven standard meteorological regimes for overland advection. The Titan 3 decays of sigma and initial rain pH differed greatly among regimes; e.g., a range of 2 pH units was spanned at x 100 km downwind and t = 2 hr. Environmentally significant pH's .5 for infrequent exposures were shown possible at X = 50 km and t 5 hr for the two least dispersive Titan 3 cases. Representative examples of downwind rainwater pH and G(X) are analyzed. Factors affecting the validity of the results are discussed.

Decreased oral bioavailability of loxoprofen at second administration in human subjects.

PubMed

Kim, I W; Choo, K S; Han, T G; Kim, K S; Chung, S J; Lee, M H; Shim, C K

2000-01-01

The objective of this study was to determine the extent of period effect on the pharmacokineitcs of loxoprofen during consecutive dosing. Loxipen and Loxonin tablets were administered to 16 healthy Korean male subjects at a single dose of 60 mg as loxoprofen sodium anhydrous in a 2 x 2 crossover investigation with a two-week wash-out phase. Concentrations of loxoprofen in plasma were measured by HPLC method for 6 h. The two formulations were found bioequivalent, but analysis of variance (ANOVA) indicated that there was a significant (p < 0.05) period effect in AUCinf (area under the plasma concentration-time curve from time zero to infinity) between the administrations. A 20% decrease in the AUC was seen at the second administration. This period effect on pharmacokinetics of loxoprofen may be relevant for the patients who need consecutive administration of the drug.

Analysis of metabolic washout of positron emitters produced during carbon ion head and neck radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helmbrecht, Stephan; Enghardt, Wolfgang; Parodi, Katia

2013-09-15

Purpose: Particle Therapy Positron Emission Tomography (PT-PET) is a suitable method for verification of therapeutic dose delivery by measurements of irradiation-induced β{sup +}-activity. Due to metabolic processes in living tissue β{sup +}-emitters can be removed from the place of generation. This washout is a limiting factor for image quality. The purpose of this study is to investigate whether a washout model obtained by animal experiments is applicable to patient data.Methods: A model for the washout has been developed by Mizuno et al. [Phys. Med. Biol. 48(15), 2269–2281 (2003)] and Tomitani et al. [Phys. Med. Biol. 48(7), 875–889 (2003)]. It ismore » based upon measurements in a rabbit in living and dead conditions. This model was modified and applied to PET data acquired during the experimental therapy project at GSI Helmholtzzentrum für Schwerionenforschung Darmstadt, Germany. Three components are expected: A fast one with a half life of 2 s, a medium one in the range of 2–3 min, and a slow component of the order of 2–3 h. Ten patients were selected randomly for investigation of the fast component. To analyze the other two components, 12 one-of-a-kind measurements from a single volunteer patient are available.Results: A fast washout on the time scale of a few seconds was not observed in the patient data. The medium processes showed a mean half life of 155.7 ± 4.6 s. This is in the expected range. Fractions of the activity not influenced by the washout were found.Conclusions: On the time scale of an in-beam or in-room measurement only the medium-time washout processes play a remarkable role. A slow component may be neglected if the measurements do not exceed 20 min after the end of the irradiation. The fast component is not observed due to the low relative blood filled volume in the brain.« less

Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Schizophrenia or Schizoaffective Disorder

PubMed Central

Kane, John M.; Correll, Christoph U.; Liang, Grace S.; Burke, Joshua; O’Brien, Christopher F.

2017-01-01

Background Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with schizophrenia/schizoaffective disorder (SCHZ) or mood disorder (mood disorder presented separately) who received up to 48 weeks of treatment. Methods KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers): 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) 1:1 from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1–7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline): and CGI-TD responders (subjects with score ≤2 [“much improved” or “very much improved”]). Treatment effect sizes (Cohen’s d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. Results Efficacy analyses were conducted in 148 subjects (DBPC) and 125 subjects (VE) with SCHZ. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -2.9, d = 0.88; 40 mg, -1.6, d = 0.52; PBO, +0.3). AIMS score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -4.2; 40 mg, -2.5). By Week 52 (end of washout), AIMS scores were returning toward baseline levels, indicating re-emergence of TD. CGI-TD mean scores were as follows: Week 6 (80 mg, 3.0, d = 0.11; 40 mg, 2.9, d = 0.23; PBO

Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Schizophrenia or Schizoaffective Disorder.

PubMed

Kane, John M; Correll, Christoph U; Liang, Grace S; Burke, Joshua; O'Brien, Christopher F

2017-08-01

Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with schizophrenia/schizoaffective disorder (SCHZ) or mood disorder (mood disorder presented separately) who received up to 48 weeks of treatment. KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers): 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) 1:1 from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1-7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline): and CGI-TD responders (subjects with score ≤2 ["much improved" or "very much improved"]). Treatment effect sizes (Cohen's d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. Efficacy analyses were conducted in 148 subjects (DBPC) and 125 subjects (VE) with SCHZ. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -2.9, d = 0.88; 40 mg, -1.6, d = 0.52; PBO, +0.3). AIMS score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -4.2; 40 mg, -2.5). By Week 52 (end of washout), AIMS scores were returning toward baseline levels, indicating re-emergence of TD. CGI-TD mean scores were as follows: Week 6 (80 mg, 3.0, d = 0.11; 40 mg, 2.9, d = 0.23; PBO, 3.2), Week 48 (80 mg, 2.2; 40 mg, 2

Efficacy of Valbenazine (NBI-98854) in Treating Subjects with Tardive Dyskinesia and Mood Disorder

PubMed Central

Correll, Christoph U.; Josiassen, Richard C.; Liang, Grace S.; Burke, Joshua; O’Brien, Christopher F.

2017-01-01

Background Valbenazine (VBZ, NBI-98854) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD). The KINECT 3 study (NCT02274558) evaluated the effects of VBZ on TD in subjects with mood disorder or schizophrenia/schizoaffective disorder (SCHZ, presented separately) who received up to 48 weeks of treatment. Methods KINECT 3 included: 6-week, double-blind, placebo (PBO)-controlled (DBPC) period (205 completers); 42-week VBZ extension (VE) period (124 completers); 4-week washout period (121 completers). Subjects entering the DBPC were randomized 1:1:1 to once-daily VBZ 80 mg, VBZ 40 mg, or PBO; stable concomitant antipsychotic medication regimens were allowed. Subjects completing the DBPC and entering the VE period were re-randomized (blinded) from PBO to VBZ (80 or 40 mg) or continued VBZ treatment at the same dose. Efficacy assessments included: mean changes from baseline in Abnormal Involuntary Movement Scale (AIMS) total score (items 1–7); mean Clinical Global Impression of Change (CGI-TD) scores; AIMS responders (subjects with ≥50% score reduction from baseline); and CGI-TD responders (subjects with score ≤2 [“much improved” or “very much improved”]). Treatment effect sizes (Cohen’s d) and numbers needed to treat (NNTs) were analyzed for DBPC outcomes. Results Efficacy analyses were conducted in 77 subjects (DBPC) and 73 subjects (VE) with a mood disorder. At Week 6 (end of DBPC), AIMS mean score improvements were greater in the VBZ groups (in a dose-related pattern) than in the PBO group (80 mg, -3.6, d = 0.94; 40 mg, -2.4, d = 0.55; PBO, -0.7). AIMS mean score changes at Week 48 (end of VE) showed continued TD improvement during long-term VBZ treatment (80 mg, -5.8; 40 mg, -4.2). By Week 52 (end of washout), AIMS mean scores in both dose groups were returning toward baseline levels, indicating re-emergence of TD. CGI-TD scores showed a similar pattern: Week 6 (80 mg, 2.7, d = 0.64; 40

Statistical comparison of pooled nitrogen washout data of various altitude decompression response groups

NASA Technical Reports Server (NTRS)

Edwards, B. F.; Waligora, J. M.; Horrigan, D. J., Jr.

1985-01-01

This analysis was done to determine whether various decompression response groups could be characterized by the pooled nitrogen (N2) washout profiles of the group members, pooling individual washout profiles provided a smooth time dependent function of means representative of the decompression response group. No statistically significant differences were detected. The statistical comparisons of the profiles were performed by means of univariate weighted t-test at each 5 minute profile point, and with levels of significance of 5 and 10 percent. The estimated powers of the tests (i.e., probabilities) to detect the observed differences in the pooled profiles were of the order of 8 to 30 percent.

The field experiments on the HTO washout from the atmosphere

DOE Office of Scientific and Technical Information (OSTI.GOV)

Golubev, A.V.; Mavrin, S.V.; Golubeva, V.N.

2015-03-15

HTO (tritiated water) wash-out from the atmosphere is one of the key processes governing the HTO transport from the atmosphere into soil and plants. Experimental studies of the HTO interaction with water drops were carried out both in laboratories and in the field. In the course of experiments, the following rain characteristics were recorded: rain intensity, size distribution of drops, and falling velocities and their dependence on drop diameter. A laser optical device was designed and used to measure the distribution of the drop radius and velocities during the period of experiment. The tritium source was placed at a heightmore » of 30 m. Rainwater samples were collected in plastic bottles and their HTO activity was determined by liquid scintillation techniques. The data obtained for the experimental values of the scavenging rate are within the range from 4.12*10{sup -5} to 1.57*10{sup -4} s{sup -1} and correspond to the precipitation intensity from 0.3 to 1.26 mm/hour. These results are in sufficiently good agreement with the results of earlier papers.« less

The wash-out of emissions from the atmosphere by precipitation

Treesearch

Ladislav Hanu& #154; ka; Eva Nov& #225; kov& #225; ; Nov& #225; kov& #225; Eva NO-VALUE

1976-01-01

We investigated the mechanism and dynamics of solid particles, emissions, and the concentrations of sulphur dioxide as integral components of the contamination of atmosphere. The only way of decontamination is the wash-out by precipitation (solid - snow, liquid - rain). We started from the items of information acquired during the studies of snow acidity in mountain...

Multiple-Breath Washout Outcomes Are Sensitive to Inflammation and Infection in Children with Cystic Fibrosis.

PubMed

Ramsey, Kathryn A; Foong, Rachel E; Grdosic, Jasmine; Harper, Alana; Skoric, Billy; Clem, Charles; Davis, Miriam; Turkovic, Lidija; Stick, Stephen M; Davis, Stephanie D; Ranganathan, Sarath C; Hall, Graham L

2017-09-01

The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. The lung clearance index is increased in the presence of lower respiratory tract inflammation and infection in infants with cystic fibrosis; however, the associations during the preschool years are unknown. We assessed the ability of the lung clearance index to detect the presence and extent of lower respiratory tract inflammation and infection in preschool children with cystic fibrosis. Ventilation distribution outcomes were assessed at 82 visits with 58 children with cystic fibrosis and at 38 visits with 31 healthy children aged 3-6 years. Children with cystic fibrosis also underwent bronchoalveolar lavage fluid collection for detection of lower respiratory tract inflammation and infection. Associations between multiple-breath washout indices and the presence and extent of airway inflammation and infection were assessed using linear mixed effects models. Lung clearance index was elevated in children with cystic fibrosis (mean [SD], 8.00 [1.45]) compared with healthy control subjects (6.67 [0.56]). In cystic fibrosis, the lung clearance index was elevated in individuals with lower respiratory tract infections (difference compared with uninfected [95% confidence interval], 0.62 [0.06, 1.18]) and correlated with the extent of airway inflammation. These data suggest that the lung clearance index may be a useful surveillance tool for monitoring the presence and extent of lower airway inflammation and infection in preschool children with cystic fibrosis.

Pharmacokinetic Interaction Between Rosuvastatin, Telmisartan, and Amlodipine in Healthy Male Korean Subjects: A Randomized, Open-label, Multiple-dose, 2-period Crossover Study.

PubMed

Son, Mijeong; Guk, Jinju; Kim, Yukyung; Woo Chae, Dong; Heo, Young-A; Soh, Dongjun; Park, Kyungsoo

2016-08-01

Rosuvastatin, a hydroxy methylglutaryl coenzyme A reductase inhibitor; telmisartan, an angiotensin receptor blocker; and amlodipine, a calcium channel inhibitor, are commonly prescribed together for the treatment of hypertension nonresponsive to monotherapy and accompanied by dyslipidemia. However, the pharmacokinetic interactions among these 3 substances are not well understood. The aim of this study was to investigate the pharmacokinetic drug-drug interactions among rosuvastatin, telmisartan, and amlodipine in a healthy Korean male population. In both parts of this randomized, open-label, multiple-dose, 2-part, 2-period crossover study, subjects aged 19 to 55 years were enrolled. In part 1, each subject received rosuvastatin 20 mg with and without 2 fixed-dose combination (FDC) tablets of telmisartan/amlodipine 40/5 mg, once daily for 9 consecutive days. In part 2, each subject received 2 FDC tablets of telmisartan/amlodipine 40/5 mg with and without rosuvastatin 20 mg, once daily for 9 consecutive days. In both parts, there was a 13-day washout period between treatments. Pharmacokinetic samples were collected up to 72 hours after the last dose in subjects who received rosuvastatin only, and up to 144 hours after the last dose in subjects who received telmisartan/amlodipine with or without rosuvastatin. Adverse events (AEs) were assessed via interviews and physical examinations. Forty-eight subjects were enrolled, of whom 19 in part 1 and 22 in part 2 completed the study. In Part 1, the 90% CIs of the geometric mean ratios (GMRs) (coadministration of rosuvastatin and telmisartan/amlodipine to monotherapy with rosuvastatin) of the primary pharmacokinetic parameters (AUCτ and Cmax,ss) were: rosuvastatin, 1.1436 to 1.3059 and 1.8970 to 2.3514, respectively; and N-desmethyl rosuvastatin, 0.8441 to 1.0200 and 1.1971 to 1.5457. In part 2, the 90% CIs of the GMRs (coadministration to monotherapy with telmisartan/amlodipine) were: telmisartan, 1.1204 to 1.4228 and 0

The contribution of site to washout and rainout: Precipitation chemistry based on sample analysis from 0.5 mm precipitation increments and numerical simulation

NASA Astrophysics Data System (ADS)

Aikawa, Masahide; Kajino, Mizuo; Hiraki, Takatoshi; Mukai, Hitoshi

2014-10-01

Datasets of precipitation chemistry at a precipitation resolution of 0.5 mm from three sites were studied to determine whether the washout and rainout mechanisms differed with site type (urban, suburban, rural). Rainout accounted for approximately one-third of the total NO3- deposition and washout contributed two-thirds, irrespective of the site type, although the washout contribution at the urban site (over 70%) was larger than that at the other two sites. The rainout mechanism and the washout mechanism both accounted for about half the total SO42- deposition at the suburban and rural sites, whereas at the urban site the rainout contribution was over 80%. A chemical transport model produced similar levels of washout and rainout contributions as the precipitation chemistry data.

The washout effects of rainfall on atmospheric particulate pollution in two Chinese cities.

PubMed

Guo, Ling-Chuan; Zhang, Yonghui; Lin, Hualiang; Zeng, Weilin; Liu, Tao; Xiao, Jianpeng; Rutherford, Shannon; You, Jing; Ma, Wenjun

2016-08-01

Though rainfall is recognized as one of the main mechanisms to reduce atmospheric particulate pollution, few studies have quantified this effect, particularly the corresponding lag effect and threshold. This study aimed to investigate the association between rainfall and air quality using a distributed lag non-linear model. Daily data on ambient PM2.5 and PM2.5-10 (particulate matter with an aerodynamic diameter less than 2.5 μm and from 2.5 to 10 μm) and meteorological factors were collected in Guangzhou and Xi'an from 2013 to 2014. A better washout effect was found for PM2.5-10 than for PM2.5, and the rainfall thresholds for both particle fractions were 7 mm in Guangzhou and 1 mm in Xi'an. The decrease in PM2.5 levels following rain lasted for 3 and 6 days in Guangzhou and Xi'an, respectively. Rainfall had a better washout effect in Xi'an compared with that in Guangzhou. Findings from this study contribute to a better understanding of the washout effects of rainfall on particulate pollution, which may help to understand the category and sustainability of dust-haze and enforce anthropogenic control measures in time. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bayesian population analysis of a washin-washout physiologically based pharmacokinetic model for acetone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moerk, Anna-Karin, E-mail: anna-karin.mork@ki.s; Jonsson, Fredrik; Pharsight, a Certara company, St. Louis, MO

2009-11-01

The aim of this study was to derive improved estimates of population variability and uncertainty of physiologically based pharmacokinetic (PBPK) model parameters, especially of those related to the washin-washout behavior of polar volatile substances. This was done by optimizing a previously published washin-washout PBPK model for acetone in a Bayesian framework using Markov chain Monte Carlo simulation. The sensitivity of the model parameters was investigated by creating four different prior sets, where the uncertainty surrounding the population variability of the physiological model parameters was given values corresponding to coefficients of variation of 1%, 25%, 50%, and 100%, respectively. The PBPKmore » model was calibrated to toxicokinetic data from 2 previous studies where 18 volunteers were exposed to 250-550 ppm of acetone at various levels of workload. The updated PBPK model provided a good description of the concentrations in arterial, venous, and exhaled air. The precision of most of the model parameter estimates was improved. New information was particularly gained on the population distribution of the parameters governing the washin-washout effect. The results presented herein provide a good starting point to estimate the target dose of acetone in the working and general populations for risk assessment purposes.« less

A simple method to reconstruct the molar mass signal of respiratory gas to assess small airways with a double-tracer gas single-breath washout.

PubMed

Port, Johannes; Tao, Ziran; Junger, Annika; Joppek, Christoph; Tempel, Philipp; Husemann, Kim; Singer, Florian; Latzin, Philipp; Yammine, Sophie; Nagel, Joachim H; Kohlhäufl, Martin

2017-11-01

For the assessment of small airway diseases, a noninvasive double-tracer gas single-breath washout (DTG-SBW) with sulfur hexafluoride (SF 6 ) and helium (He) as tracer components has been proposed. It is assumed that small airway diseases may produce typical ventilation inhomogeneities which can be detected within one single tidal breath, when using two tracer components. Characteristic parameters calculated from a relative molar mass (MM) signal of the airflow during the washout expiration phase are analyzed. The DTG-SBW signal is acquired by subtracting a reconstructed MM signal without tracer gas from the signal measured with an ultrasonic sensor during in- and exhalation of the double-tracer gas for one tidal breath. In this paper, a simple method to determine the reconstructed MM signal is presented. Measurements on subjects with and without obstructive lung diseases including the small airways have shown high reliability and reproducibility of this method.

Effects of cereal bar containing polydextrose on subjective feelings of appetite and energy intake in overweight adults over 15 d.

PubMed

Martinelli, Marcela; Hick, Emilia; Walz, Florencia; Drago, Silvina R

2018-01-18

The effects of 15 d polydextrose (16.7 g) consumption on energy intake (EI) and appetite feelings were investigated. Overweight adults consumed a polydextrose-bar or a control-bar matched in energy content as a midmorning snack for 15 consecutive days in a single-blind, randomised, crossover design. The two 15-d intervention periods were separated by a 15-d washout period. On the day 1 and the day 15 of each intervention period, energy intake (primary outcome) and appetite feelings (secondary outcome) were assessed. There were not significant main effects of the day, type of bar, or their interaction for EI (at lunchtime test meal, at rest of the day, or at total daily) or subjective feelings (hunger, desire to eat, fullness, and prospective food consumption) during the satiation and satiety periods. The results showed the consumption of polydextrose-bar during 15 d did not significantly affect energy intake and subjective feelings of appetite in overweight adults.

Evaluation of a linear washout for simulator motion cue presentation during landing approach

NASA Technical Reports Server (NTRS)

Parrish, R. V.; Martin, D. J., Jr.

1975-01-01

The comparison of a fixed-base versus a five-degree-of-freedom motion base simulation of a 737 conventional take-off and landing (CTOL) aircraft performing instrument landing system (ILS) landing approaches was used to evaluate a linear motion washout technique. The fact that the pilots felt that the addition of motion increased the pilot workload and this increase was not reflected in the objective data results, indicates that motion cues, as presented, are not a contributing factor to root-mean-square (rms) performance during the landing approach task. Subjective results from standard maneuvering about straight-and-level flight for specific motion cue evaluation revealed that the longitudinal channels (pitch and surge) possibly the yaw channel produce acceptable motions. The roll cue representation, involving both roll and sway channels, was found to be inadequate for large roll inputs, as used for example, in turn entries.

Similar Hydrodynamic and Morphological Changes in the Aqueous Humor Outflow Pathway after Washout and Y27632 Treatment in Monkey Eyes

PubMed Central

Lu, Zhaozeng; Zhang, Yuyan; Freddo, Thomas F.; Gong, Haiyan

2011-01-01

Our previous studies in bovine eyes demonstrated that the structural correlate to the increase in outflow facility after either Rho-kinase inhibitor Y-27632 (Y27) treatment or washout appeared to be separation between the juxtacanalicular tissue (JCT) and inner wall (IW) of the aqueous plexus, the bovine equivalent of Schlemm's canal (SC). While these findings suggest that Y27 and washout may increase outflow facility through a similar mechanism, the anatomy of bovine outflow pathway differs considerably from both the human and monkey outflow pathway; however, only the human eye does not exhibit washout. In light of this, we compared the effects of Y27 and washout on outflow facility, hydrodynamic patterns of outflow, and the morphology of the IW and JCT in monkey eyes, given that their anatomy is closer to human eyes. Twelve freshly enucleated monkey eyes were used in this study. Eyes were perfused with Dulbecco's PBS containing 5.5 mM glucose (GPBS) to establish a baseline facility at 15 mmHg. Four eyes were perfused for a short-duration (30 min) as a control, 4 eyes for a long-duration (180 min) to induce washout, and 4 eyes with GPBS+50 μM Y27 for 30 min. All eyes were then perfused with fluorescent microspheres (0.5μm; 0.002%) to label the hydrodynamic patterns of outflow and then perfusion-fixed. Confocal images of frontal sections were taken along the IW of SC. The total length (TL) and the tracer decorated length (FL) of the IW were measured to calculate the average percent effective filtration length (PEFL=FL/TL). Sections with SC were examined by light and electron microscopy. The TL of the IW and the length exhibiting separation (SL) in the JCT were measured to calculate the average percent separation length (PSL= SL/TL). Outflow facility increased 149.2% (p<0.01) from baseline after washout during long-duration perfusion, and 114.9% (p=0.004) after Y27 treatment, but did not change significantly after short-duration perfusion in control eyes (p=0

Influence of thyroid gland status on the thyroglobulin cutoff level in washout fluid from cervical lymph nodes of patients with recurrent/metastatic papillary thyroid cancer.

PubMed

Lee, Jun Ho; Lee, Hyun Chul; Yi, Ha Woo; Kim, Bong Kyun; Bae, Soo Youn; Lee, Se Kyung; Choe, Jun-Ho; Kim, Jung-Han; Kim, Jee Soo

2016-04-01

The influence of serum thyroglobulin (Tg) and thyroidectomy status on Tg in fine-needle aspiration cytology (FNAC) washout fluid is unclear. A total of 282 lymph nodes were prospectively subjected to FNAC, fine-needle aspiration (FNA)-Tg measurement, and frozen and permanent biopsies. We evaluated the diagnostic performance of several predetermined FNA-Tg cutoff values for recurrence/metastasis in lymph nodes according to thyroidectomy status. The diagnostic performance of FNA-Tg varied according to thyroidectomy status. The optimized cutoff value of FNA-Tg was 2.2 ng/mL. However, among FNAC-negative lymph nodes, the FNA-Tg cutoff value of 0.9 ng/mL showed better diagnostic performance in patients with a thyroid gland. An FNA-Tg/serum-Tg cutoff ratio of 1 showed the best diagnostic performance in patients without a thyroid gland. Applying the optimal cutoff values of FNA-Tg according to thyroid gland status and serum Tg level facilitates the diagnostic evaluation of neck lymph node recurrences/metastases in patients with papillary thyroid carcinoma (PTC). © 2015 Wiley Periodicals, Inc. Head Neck 38: E1705-E1712, 2016. © 2015 Wiley Periodicals, Inc.

Cadaveric renal preservation with hyperosmolar, intracellular hypothermic washout solution and cold storage.

PubMed

Diethelm, A G; Blackstone, E H

1978-07-01

All 54 kidneys obtained from heart-beating cadavers functioned when preserved by a brief washout using a hypothermic, hyperosmolar, hyperkalemic perfusate, followed by cold storage. The duration of preservation ranged from two hours and 57 minutes to 39 hours and 47 minutes. Two other kidneys retrieved from a nonheart-beating cadaver and preserved by the same technique failed to function because of irreversible acute tubular necrosis. Fifty-six consecutive transplant patients were divided into four groups according to the period of preservation. There was no correlation between graft rejection, frequency of post-transplant dialysis, long term graft function and survival time, when the duration of preservation was less than 24 hours. The advantages of this technique included technical simplicity, low cost, minimal risk of graft infection and easy transportation. The two primary disadvantages were an apparent 24 to 30 hour limit of organ preservation with prompt function and the inability to determine intrarenal perfusion pressure during preservation, thereby missing an important parameter of graft viability.

Love-type seam-waves in washout models of coal seams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Breitzke, M.; Dresen, L.

The propagation of Love seam-waves across washouts of coal seams was studied by calculating synthetic seismograms with a finite-difference method. Seam interruption, seam end and seam thinning models ere investigated. The horizontal offset, the dip of the discontinuities and the degree of erosion served as variable parameters. Maximum displacement amplitudes, relative spectral amplitudes and phase and group slowness curves were extracted from the synthetic seismograms. Both seam interruption and seam thinning reduce the maximum displacement amplitudes of the transmitted Love seam-waves. The degree of amplitude reduction depends on the horizontal offset and the degree of erosion. It is four timesmore » greater for a total seam interruption than for an equivalent seam thinning with a horizontal offset of four times the seam thickness. In a seam cut vertically, the impedance contrast between the coal and the washout filling determines the maximum displacement amplitudes of the reflected Love seam-waves. They diminish by a maximum factor of four in oblique interruption zone discontinuities with a dip of maximum 27/sup 0/, and by a maximum factor of ten in a seam thinning with a degree of erosion of at least 22%.« less

Microcrustacea in flowing water - experimental-analysis of washout times and a field-test

USGS Publications Warehouse

Richardson, W.B.

1992-01-01

1. Flow-chamber experiments were conducted to evaluate the ability of microcrustacea to maintain position in moving water. These results were compared to distributions of zooplankton and water velocity in a stream pool to determine the relationship of animal density to water movement and swimming ability.^2. Cladocerans exhibited negative rheotaxis (directed behaviour against a current) but poor ability to maintain position at velocities >2.5 Cm s-1. Daphnia and scapholeberis were better at avoiding washout than moina and diaphanosoma. At velocities 2.5 Cm s-1, scapholeberis >3.2 Cm s-1 and eucyclops >7.75 Cm s-1. Washout time of daphnia and scapholeberis was positively related to body size and negatively to water velocity and possession of eggs. Washout was inversely related to water velocity for eucyclops.^4. Highest densities of microcrustacea in a stream pool were found in non-flowing or downstream zones of the pool. Benthic (hydracarina, harpacticoid copepods, ostracods) and fast-swimming (cyclopoids) forms were most common in flowing zones. Facultatively benthic cladocera were abundant in regions of no flow. Rotifers and immature copepods were most abundant at the downstream end of the pool.^5. Behavioural mechanisms for remaining in stream pools at times of high flow appear to include: (i) flow avoidance (simocephalus, chydorus, scapholeberis and cyclopoids), (ii) use of benthic habitat (ostracods, harpacticoids, hydracarina), (iii) strong swimming ability (cyclopoids).

Thyroglobulin assay in fluids from lymph node fine needle-aspiration washout: influence of pre-analytical conditions.

PubMed

Casson, Florence Boux de; Moal, Valérie; Gauchez, Anne-Sophie; Moineau, Marie-Pierre; Sault, Corinne; Schlageter, Marie-Hélène; Massart, Catherine

2017-04-01

The aim of this study was to evaluate the pre-analytical factors contributing to uncertainty in thyroglobulin measurement in fluids from fine-needle aspiration (FNA) washout of cervical lymph nodes. We studied pre-analytical stability, in different conditions, of 41 samples prepared with concentrated solutions of thyroglobulin (FNA washout or certified standard) diluted in physiological saline solution or buffer containing 6% albumin. In this buffer, over time, no changes in thyroglobulin concentrations were observed in all storage conditions tested. In albumin free saline solution, thyroglobulin recovery rates depended on initial sample concentrations and on modalities of their conservation (in conventional storage tubes, recovery mean was 56% after 3 hours-storage at room temperature and 19% after 24 hours-storage for concentrations ranged from 2 to 183 μg/L; recovery was 95%, after 3 hours or 24 hours-storage at room temperature, for a concentration of 5,656 μg/L). We show here that these results are due to non-specific adsorption of thyroglobulin in storage tubes, which depends on sample protein concentrations. We also show that possible contamination of fluids from FNA washout by plasma proteins do not always adequately prevent this adsorption. In conclusion, non-specific adsorption in storage tubes strongly contributes to uncertainty in thyroglobulin measurement in physiological saline solution. It is therefore recommended, for FNA washout, to use a buffer containing proteins provided by the laboratory.

[Determination of polioksin B in the air environment and in washouts from skin of operators by HPLC].

PubMed

Volkova, V N; Mukhina, L P; Chistova, Zh A; Fedorova, S G

Polyoxin B being an effective inhibitor of synthesis of chitin of the cell wall of many phytopathogenic fungi, is recommended as a fungicide for control of phytopathogenic organisms that cause damage to crop. For the determination of the exposure of employees working with pesticides there was developed the method of the measurement of concentrations of polyoxin B in air of working area, atmospheric air of populated areas and washouts from the operators ’ integuments, based on high performance liquid chromatography with ultraviolet detector (detection wavelength of270 nm), including sampling air environment in the sorption tube ORBO-44, filled with sorbent XAD-2, extraction of the sorbent with polyoxin by a mixture of carbinol-water (in a ratio of 95:5,on volume), washout from the surface of the skin with ethyl alcohol by way of washing, concentrating, quantitative chromatographic analysis. Lower limits of the quantification ofpolyoxin B in the air ofworking area - 0.2 mg/m at the aspiration of 2 dm of air, atmospheric air - 0.016 mg/m at the aspiration of 25 dm of air, in washouts from the operators’ integuments - 0.4 pg/wash, the linear range of the defined concentrations accounted for of 0.2 - 2.4 pg/cm, the total error of measurement of the concentrations of polyoxin B in air is 17%; in washouts from the operators’ integuments - 16%. The developed method was approbated for the determination of polyoxin in samples of air of working zone, atmospheric air within the sanitary gap, washouts from the operators ’ integuments and air drift samples taken under processing of roses in the hothouse and in the monitoring of the phytosanitary condition of the plants every other day after treatment.

Tracer Studies In A Laboratory Beach Subjected To Waves

EPA Science Inventory

This work investigated the washout of dissolved nutrients from beaches due to waves by conducting tracer studies in a laboratory beach facility. The effects of waves were studied in the case where the beach was subjected to the tide, and that in which no tidal action was present...

Experimental and calculated characteristics of three wings of NACA 64-210 and 65-210 airfoil sections with and without 2 degree washout

NASA Technical Reports Server (NTRS)

Sivells, James C

1947-01-01

Report presents the results of an investigation conducted to determine some of the effects of airfoil section and washout on the experimental and calculated characteristics of 10-percent-thick wings. Three wings of aspect ratio 9 and ratio of root chord to tip chord 2.5 were tested. One wing had NACA 64-210 sections and 2 degree washout, the second had NACA 65-210 sections and 2 degree washout, and the third had NACA 65-210 sections and 0 degree washout. It was found that the experimental characteristics of the wings could be satisfactorily predicted from calculations based upon two-dimensional data when the airfoil contours of the wings conformed to the true airfoil sections with the same high degree of accuracy as the two-dimensional models.

Infant multiple breath washout using a new commercially available device: Ready to replace the previous setup?

PubMed

Kentgens, Anne-Christianne; Guidi, Marisa; Korten, Insa; Kohler, Lena; Binggeli, Severin; Singer, Florian; Latzin, Philipp; Anagnostopoulou, Pinelopi

2018-05-01

Multiple breath washout (MBW) is a sensitive test to measure lung volumes and ventilation inhomogeneity from infancy on. The commonly used setup for infant MBW, based on ultrasonic flowmeter, requires extensive signal processing, which may reduce robustness. A new setup may overcome some previous limitations but formal validation is lacking. We assessed the feasibility of infant MBW testing with the new setup and compared functional residual capacity (FRC) values of the old and the new setup in vivo and in vitro. We performed MBW in four healthy infants and four infants with cystic fibrosis, as well as in a Plexiglas lung simulator using realistic lung volumes and breathing patterns, with the new (Exhalyzer D, Spiroware 3.2.0, Ecomedics) and the old setup (Exhalyzer D, WBreath 3.18.0, ndd) in random sequence. The technical feasibility of MBW with the new device-setup was 100%. Intra-subject variability in FRC was low in both setups, but differences in FRC between the setups were considerable (mean relative difference 39.7%, range 18.9; 65.7, P = 0.008). Corrections of software settings decreased FRC differences (14.0%, -6.4; 42.3, P = 0.08). Results were confirmed in vitro. MBW measurements with the new setup were feasible in infants. However, despite attempts to correct software settings, outcomes between setups were not interchangeable. Further work is needed before widespread application of the new setup can be recommended. © 2018 Wiley Periodicals, Inc.

Compartmental analysis of washout effect in rat brain: in-beam OpenPET measurement using a 11C beam

NASA Astrophysics Data System (ADS)

Hirano, Yoshiyuki; Kinouchi, Shoko; Ikoma, Yoko; Yoshida, Eiji; Wakizaka, Hidekazu; Ito, Hiroshi; Yamaya, Taiga

2013-12-01

In-beam positron emission tomography (PET) is expected to enable visualization of a dose verification using positron emitters (β+ decay). For accurate dose verification, correction of the washout of the positron emitters should be made. In addition, the quantitative washout rate has a potential usefulness as a diagnostic index, but modeling for this has not been studied yet. In this paper, therefore, we applied compartment analyses to in-beam PET data acquired by our small OpenPET prototype, which has a physically opened field-of-view (FOV) between two detector rings. A rat brain was located at the FOV and was irradiated by a 11C beam. Time activity curves of the irradiated field were measured immediately after the irradiations, and the washout rate was obtained based on two models: the two-washout model (medium decay, k2m; slow decay, k2s) developed in a study of rabbit irradiation; and the two-compartment model used in nuclear medicine, where efflux from tissue to blood (k2), influx (k3) and efflux (k4) from the first to second compartments in tissue were evaluated. The observed k2m and k2s were 0.34 and 0.005 min-1, respectively, which was consistent with the rabbit study. Also k2m was close to the washout rate in cerebral blood flow (CBF) measurements by dynamic PET with 15O-water, while, k2, k3, and k4 were 0.16, 0.15 and 0.007 min-1. Our present work suggested the dynamics of 11C might be relevant to CBF or permeability of a molecule containing 11C atoms might be regulated by a transporter because the k2 was relatively low compared with a simple diffusion tracer.

Isocapnic hyperventilation shortens washout time for sevoflurane - an experimental in vivo study.

PubMed

Hallén, K; Stenqvist, O; Ricksten, S-E; Lindgren, S

2016-10-01

Isocapnic hyperventilation (IHV) is a method that fastens weaning from inhalation anaesthesia by increasing airway concentration of carbon dioxide (CO2 ) during hyperventilation (HV). In an animal model, we evaluated a technique of adding CO2 directly to the breathing circuit of a standard anaesthesia apparatus. Eight anaesthetised pigs weighing 28 ± 2 kg were intubated and mechanically ventilated. From a baseline ventilation of 5 l/min, HV was achieved by doubling minute volume and fresh gas flow. Respiratory rate was increased from 15 to 22/min. The CO2 absorber was disconnected and CO2 was delivered (DCO2 ) to the inspiratory limb of a standard breathing circuit via a mixing box. Time required to decrease end-tidal sevoflurane concentration from 2.7% to 0.2% was defined as washout time. Respiration and haemodynamics were monitored by blood gas analysis, spirometry, electric impedance tomography and pulse contour analysis. A DCO2 of 261 ± 19 ml/min was necessary to achieve isocapnia during HV. The corresponding FICO2 -level remained stable at 3.1 ± 0.3%. During IHV, washout of sevoflurane was three times faster, 433 ± 135 s vs. 1387 ± 204 s (P < 0.001). Arterial CO2 tension and end-tidal CO2 , was 5.2 ± 0.4 kPa and 5.6 ± 0.4%, respectively, before IHV and 5.1 ± 0.3 kPa and 5.7 ± 0.3%, respectively, during IHV. In this experimental in vivo model of isocapnic hyperventilation, the washout time of sevoflurane anaesthesia was one-third compared to normal ventilation. The method for isocapnic hyperventilation described can potentially be transferred to a clinical setting with the intention to decrease emergence time from inhalation anaesthesia. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Calcitonin assay in wash-out fluid after fine-needle aspiration biopsy in patients with a thyroid nodule and border-line value of the hormone.

PubMed

Massaro, F; Dolcino, M; Degrandi, R; Ferone, D; Mussap, M; Minuto, F; Giusti, M

2009-04-01

Assaying calcitonin (CT) in the wash-out fluid from fine-needle aspiration biopsies (CT-FNAB) could be useful in the diagnosis of medullary thyroid carcinoma (MTC). The aim of this study was to correlate serum CT with cytology and CT-FNAB. Twenty-seven subjects (age range 27-75 yr) were studied. FNAB was performed in a thyroid nodule (no.=16) or lymph-node (no.=1 previously operated on for MTC) or in the prevalent nodule of multinodular goiters (no.=10). CT-FNAB values obtained in 37 subjects with normal serum CT (<10 ng/l) who underwent FNAB for thyroid nodules served as a negative control. In these subjects, CTFNAB values were 8.2+/-6.4 ng/l (range 2-30 ng/l). In patients with a thyroid nodule under evaluation for MTC, serum CT and CT-FNAB values were 14.5+/-3.9 ng/l (range 10-24 ng/l) and 16.4+/-29.8 ng/l (range 2-144 ng/l), respectively. In 4 patients, CT-FNAB values were higher than the highest values found in our negative controls (30 ng/l), but cytology results were compatible with a benign thyroid lesion and pentagastrin testing was negative. In 3 cases with CT-FNAB <30 ng/l, cytology was indicative of an indeterminate or probably follicular malignant lesion and histology was negative for MTC. None of the other subjects in whom pentagastrin testing was conducted showed serum CT values >100 ng/l. Our data do not show any correlation between CT-FNAB and serum CT. In conclusion, borderline CT values in patients with thyroid nodules are not rare. Our experience suggests that CT-FNAB does not have the same importance as that reported in the literature for thyroglobulin and PTH assay in wash-out fluid after FNAB in malignant thyroid and hyperfunctioning parathyroid lesions.

Preparation of hydroxyapatite/collagen injectable bone paste with an anti-washout property utilizing sodium alginate. Part 1: influences of excess supplementation of calcium compounds.

PubMed

Sato, Taira; Kikuchi, Masanori; Aizawa, Mamoru

2017-03-01

The anti-washout property, viscosity, and cytocompatibility to an osteoblastic cell line, MG-63, of anti-washout pastes were investigated. Mixing a hydroxyapatite/collagen bone-like nanocomposite (HAp/Col), an aqueous solution of sodium alginate (Na-Alg), which is a paste hardening and lubricant agent, and supplementation of calcium carbonate or calcium citrate (Ca-Cit) as a calcium resource for the hardening reaction realized an injectable bone paste. Adding Ca-Cit at a concentration greater than eight times the Ca 2+ ion concentration to Na-Alg improved the anti-washout property. Although the viscosity test indicated a gradual increase in the paste viscosity as the calcium compounds increased, pastes with excess supplementation of calcium compounds exhibited injectability through a syringe with a 1.8 mm inner diameter, realizing an injectable bone filler. Furthermore, the anti-washout pastes with Ca-Cit had almost the same cell proliferation rate as that of the HAp/Col dense body. Therefore, HAp/Col injectable anti-washout pastes composed of the HAp/Col, Na-Alg, and Ca-Cit are potential candidates for bioresorbable bone filler pastes.

The Efficacy of an Air-Cooling Vest to Reduce Thermal Strain for Light Armour Vehicle Personnel

DTIC Science & Technology

2007-01-01

4 2.9.4 Thermal Comfort Measurements .................................................................... 4 2.9.5...5 3.2 Thermal Comfort ........................................................................................................... 5...period for each subject following a 1-min washout period. 2.9.4 Thermal Comfort Measurements Subjects were asked to provide a subjective

Lactobacillus gasseri SBT2055 reduces postprandial and fasting serum non-esterified fatty acid levels in Japanese hypertriacylglycerolemic subjects.

PubMed

Ogawa, Akihiro; Kadooka, Yukio; Kato, Ken; Shirouchi, Bungo; Sato, Masao

2014-02-19

Lactobacillus gasseri SBT2055 (LG2055) inhibits dietary fat absorption in rats and exerts preventive effects on abdominal adiposity in rats and humans. The present study aimed to evaluate the effects of LG2055 on postprandial serum lipid responses in Japanese subjects with hypertriacylglycerolemia after the intake of oral fat-loading test (OFLT) meals. We conducted a single-blind, placebo-controlled, within-subject, repeated-measure intervention trial. Twenty subjects initially ingested the fermented milk (FM) without LG2055 for 4 weeks (control FM period), followed by a 4-week washout period, and then consumed FM containing LG2055 for 4 weeks (active FM period). The subjects were asked to consume FM at 200 g/day. At the end of each 4-week period, an 8-h OFLT was conducted. Blood samples were collected at fasting and every hour for 8 h after OFLT meal intake. Thereafter, postprandial serum non-esterified fatty acid (NEFA) and triacylglycerol (TAG) levels and fasting blood parameters were measured. The OFLT showed that the postprandial serum NEFA levels from 120 to 480 min and the postprandial serum TAG level at 120 min in the active FM period were significantly (P < 0.05) lower than those in the control FM period. The fasting serum NEFA level in the active FM period significantly (P < 0.001) decreased at week 4 from the initial period compared with the control FM period. The consumption of probiotic LG2055 reduced postprandial and fasting serum NEFA levels, suggesting its possible contribution to the reduction of the risk for obesity and type 2 diabetes mellitus. UMIN000011605.

Free thyroxine in needle washout after fine needle aspiration biopsy of toxic thyroid nodules.

PubMed

Raikov, Nikolai; Nonchev, Boyan; Chaushev, Borislav; Vjagova, Diyana; Todorov, Svetoslav; Bocheva, Yana; Malceva, Daniela; Vicheva, Snejinka; Raikova, Asyia; Argatska, Antoaneta; Raikov, Miroslav

2016-01-01

The main diagnostic tool for toxic adenomas (TA) is radionuclide imaging indicated in patients with evidence of thyroid nodules in combination with thyrotoxic syndrome. Thyroid ultrasound and fine-needle aspiration biopsy (FNAB) are widely used for the valuation of thyroid masses. There is no literature data concerning the utility of FNAB and related tests for the diagnosis of hyperfunctioning thyroid nodules. The purpose of this study is to determine the levels of free thyroxine (FT4) in the needle washout after FNAB of hot thyroid nodules. The results of our study show that the FT4 levels in needle washout from TA were significantly higher than the surrounding parenchyma and correlated with the hormonal changes in patients with thyroid hyperfunctioning nodules. Further studies on a large number of patients are needed to refine the diagnostic value of this method and evaluate its importance in quantitative risk assessment of thyroid autonomy.

Delafloxacin Pharmacokinetics in Subjects With Varying Degrees of Renal Function.

PubMed

Hoover, Randall K; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K; Quintas, Megan; Cammarata, Sue K

2018-04-01

Delafloxacin, a fluoroquinolone, has activity against gram-positive organisms including methicillin-resistant Staphylococcus aureus and fluoroquinolone-susceptible and -resistant gram-negative organisms. This study was conducted to determine delafloxacin pharmacokinetics after a single intravenous infusion or oral dose administration in subjects with varying degrees of renal function. The study was an open-label, parallel-group crossover study in subjects with normal renal function or with mild, moderate, or severe renal impairment. Subjects received 300 mg delafloxacin intravenously, placebo intravenously, and 400 mg delafloxacin orally in 3 periods separated by ≥14-day washouts. Blood and urine pharmacokinetic parameters were calculated using noncompartmental methods. Delafloxacin total clearance decreased with decreasing renal function, with a corresponding increase in AUC 0-∞ . After intravenous administration, mean total clearance was 13.7 and 7.07 L/h, and mean AUC 0-∞ was 22.6 and 45.0 μg·h/mL in normal and severe renal subjects, respectively. Mean renal clearance as determined by urinary excretion was 6.03 and 0.44 L/h in normal and severe renal impairment subjects, respectively. Total clearance exhibited linear relationships to eGFR and CL CR . Similar observations were found after oral administration of delafloxacin. Single doses of delafloxacin 300 mg intravenously and 400 mg orally were well tolerated in all groups. In conclusion, renal insufficiency has an effect on delafloxacin clearance; a dosing adjustment for intravenous dosing is warranted for patients with severe renal impairment (eGFR < 30 mL/min). © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

A kinesthetic washout filter for force-feedback rendering.

PubMed

Danieau, Fabien; Lecuyer, Anatole; Guillotel, Philippe; Fleureau, Julien; Mollet, Nicolas; Christie, Marc

2015-01-01

Today haptic feedback can be designed and associated to audiovisual content (haptic-audiovisuals or HAV). Although there are multiple means to create individual haptic effects, the issue of how to properly adapt such effects on force-feedback devices has not been addressed and is mostly a manual endeavor. We propose a new approach for the haptic rendering of HAV, based on a washout filter for force-feedback devices. A body model and an inverse kinematics algorithm simulate the user's kinesthetic perception. Then, the haptic rendering is adapted in order to handle transitions between haptic effects and to optimize the amplitude of effects regarding the device capabilities. Results of a user study show that this new haptic rendering can successfully improve the HAV experience.

Kinetics of Uptake and Washout of Lidocaine in Rat Sciatic Nerve In Vitro

PubMed Central

Leeson, Stanley; Strichartz, Gary

2012-01-01

Background The potency and efficacy of local anesthetics injected clinically for peripheral nerve block depends strongly on the rate of neural drug uptake. However, since diffusion into surrounding tissues and removal by the vascular system are major factors in the overall distribution of lidocaine in vivo, true kinetics of drug/neural tissue interactions must be studied in the absence of those confounding factors. Methods Uptake: Ensheathed or desheathed isolated rat sciatic nerves were exposed to [14C]-lidocaine for 0-180min and then removed and the lidocaine content of nerve and sheath analyzed. Washout: Isolated nerves were soaked in [14C]-lidocaine for 60min and then placed in lidocaine-free solution for 0-30min, with samples removed at different times to assess the drug content. Experimental variables included the effects of the ensheathing epineurium, lidocaine concentration, pH, presence of CO2-bicarbonate, and incubation duration. Results The equilibrium uptake of lidocaine increased with incubation time, concentration and the fraction of molecules in the non-ionized form. The uptake rate was unaffected by drug concentration, but was about halved by the presence of the epineurial sheath, with the washout rate slowed less. Slight alkalinization, from pH 6.8 to pH 7.4, by bicarbonate-CO2 buffer or a non-bicarbonate buffer, enhanced the neural uptake, and to the same degree. The washout of lidocaine was faster after shorter incubations at high concentrations than when equal amounts of lidocaine were taken up after long incubations at low lidocaine concentrations. Conclusion Lidocaine enters a nerve by a process other than free diffusion, through an epineurial sheath that is a slight obstacle. Given the rapid entry in vitro compared to the much smaller and transient content measured in vivo, it seems highly unlikely that lidocaine equilibrates with the nerve during a peripheral blockade. PMID:23400993

Baru almond improves lipid profile in mildly hypercholesterolemic subjects: a randomized, controlled, crossover study.

PubMed

Bento, A P N; Cominetti, C; Simões Filho, A; Naves, M M V

2014-12-01

The usual consumption of nuts reduces cardiovascular diseases (CVD) risk by improving serum lipids and oxidation status. Baru almonds (Dipteryxalata Vog.), a native species of Brazilian Savannah, have considerable contents of monounsaturated fatty acids (MUFA), dietary fiber, vitamin E and zinc, which could exert positive effects in serum lipids and markers of oxidation. However, there is no study about the effect of their consumption on human health. Thus, the aim of this study was to evaluate the effect of baru almonds supplementation on lipid profile and oxidation of mildly hypercholesterolemic subjects. A randomized, crossover, placebo controlled study was performed with 20 mildly hypercholesterolemic subjects (total cholesterol (TC) mean ±SEM = 5.8 ± 0.2 mmol/L). The assay had 2 periods of 6 weeks each and a 4-week washout period between the treatments. Subjects were randomly allocated in alternated periods receiving the following treatments per period: supplementation with 20 g/day of baru almonds or placebo (1 corn starch capsule/day). Compared to placebo, supplementation of baru almonds reduced TC (-8.1 ± 2.4%, P = 0.007), low-density lipoprotein cholesterol (LDL-c) (-9.4 ± 2.4%, P = 0.006) and non-high-density lipoprotein cholesterol (non-HDL-c) (-8.1 ± 3.0%, P = 0.013). There were no significant changes on the oxidation biomarkers evaluated. Dietary supplementation of mildly hypercholesterolemic subjects with baru almonds improved serum lipid parameters, so that this food might be included in diets for reducing the CVD risk. Brazilian Registry of Clinical Trials (ReBEC) (website: http://www.ensaiosclinicos.gov.br). Register number: RBR-4zdy9p. Copyright © 2014 Elsevier B.V. All rights reserved.

A glass of water immediately increases gastric pH in healthy subjects.

PubMed

Karamanolis, George; Theofanidou, Ioanna; Yiasemidou, Marina; Giannoulis, Evangelos; Triantafyllou, Konstantinos; Ladas, Spiros D

2008-12-01

Onset of action of antisecretory agents is of pivotal importance for patients with gastroesophageal reflux disease (GERD) treated "on-demand." To study the acute effect of acid-inhibiting drugs and water administration on gastric pH. A cross-over study was performed in 12 H. pylori (-), healthy subjects (6 men; mean age: 26 years). A single oral dose of the following agents was received with a wash-out period between each study: a glass of water (200 ml), antacid, ranitidine, omeprazole, esomeprazole, and rabeprazole. Gastric pH was recorded for 6 h after drug intake. Water increased gastric pH >4 in 10/12 subjects after 1 min. The time (median) needed to pH >4 was for: antacid 2 min, ranitidine 50 min, omeprazole 171 min, esomeprazole 151 min, and rabeprazole 175 min. Gastric pH >4 lasted for 3 min after water and for 12 min after antacids; it remained >4 until the end of recording in: 4/12 subjects with ranitidine, 11/12 with rabeprazole, and all with omeprazole and esomeprazole. Water and antacid immediately increased gastric pH, while PPIs showed a delayed but prolonged effect compared to ranitidine.

Pharmacokinetics of neratinib during coadministration with lansoprazole in healthy subjects

PubMed Central

DiPrimeo, Daniel; Li, Ai; Obaidi, Mohammad; Swearingen, Dennis; Wong, Alvin

2016-01-01

Aims To evaluate the effect of lansoprazole, a proton‐pump inhibitor, on the absorption, pharmacokinetics, and safety of neratinib, a pan‐HER tyrosine kinase inhibitor, in healthy subjects. Methods This was an open‐label, two‐period, fixed‐sequence study. Fifteen healthy adult subjects received a single oral dose of neratinib 240 mg (Period 1), followed by a washout period, then oral lansoprazole 30 mg once daily for 7 days and a single dose of neratinib 240 mg on Day 5 (Period 2). Pharmacokinetic sampling was performed for 72 h following each neratinib dose. Plasma neratinib concentration–time data were analysed using noncompartmental methods. Geometric mean ratios for AUC0–t, AUC0–inf, and peak plasma concentrations (Cmax) for neratinib plus lansoprazole vs. neratinib were used to assess the magnitude of the drug–drug interaction if the 90% confidence intervals were outside 80.00–125.00%. Results Neratinib geometric least‐squares mean (LSM) Cmax was reduced from 84.5 ng ml−1 with neratinib alone to 24.5 ng ml−1 with neratinib plus lansoprazole. The extent of exposure to neratinib was also decreased: geometric LSM AUC0–t was 1478 ng ml−1 h with neratinib vs. 426 ng ml−1 h with neratinib plus lansoprazole, and geometric LSM AUC0–inf was 1557 ng ml−1 h vs. 542 ng ml−1 h, respectively. Mean t½ was similar with both treatments (approximately 14 h). Geometric mean ratios 90% confidence intervals for AUC0–t, AUC0–inf and Cmax fell outside the prespecified equivalence range (80.0–125.0%). Treatment‐emergent adverse events, all mild, were reported by five (33%) subjects. Conclusions Coadministration of lansoprazole with neratinib reduced the rate and extent of neratinib exposure in healthy subjects. PMID:27628584

Pharmacokinetics of neratinib during coadministration with lansoprazole in healthy subjects.

PubMed

Keyvanjah, Kiana; DiPrimeo, Daniel; Li, Ai; Obaidi, Mohammad; Swearingen, Dennis; Wong, Alvin

2017-03-01

To evaluate the effect of lansoprazole, a proton-pump inhibitor, on the absorption, pharmacokinetics, and safety of neratinib, a pan-HER tyrosine kinase inhibitor, in healthy subjects. This was an open-label, two-period, fixed-sequence study. Fifteen healthy adult subjects received a single oral dose of neratinib 240 mg (Period 1), followed by a washout period, then oral lansoprazole 30 mg once daily for 7 days and a single dose of neratinib 240 mg on Day 5 (Period 2). Pharmacokinetic sampling was performed for 72 h following each neratinib dose. Plasma neratinib concentration-time data were analysed using noncompartmental methods. Geometric mean ratios for AUC 0-t , AUC 0-inf , and peak plasma concentrations (C max ) for neratinib plus lansoprazole vs. neratinib were used to assess the magnitude of the drug-drug interaction if the 90% confidence intervals were outside 80.00-125.00%. Neratinib geometric least-squares mean (LSM) C max was reduced from 84.5 ng ml -1 with neratinib alone to 24.5 ng ml -1 with neratinib plus lansoprazole. The extent of exposure to neratinib was also decreased: geometric LSM AUC 0-t was 1478 ng ml -1  h with neratinib vs. 426 ng ml -1  h with neratinib plus lansoprazole, and geometric LSM AUC 0-inf was 1557 ng ml -1  h vs. 542 ng ml -1  h, respectively. Mean t ½ was similar with both treatments (approximately 14 h). Geometric mean ratios 90% confidence intervals for AUC 0-t , AUC 0-inf and C max fell outside the prespecified equivalence range (80.0-125.0%). Treatment-emergent adverse events, all mild, were reported by five (33%) subjects. Coadministration of lansoprazole with neratinib reduced the rate and extent of neratinib exposure in healthy subjects. © 2016 The British Pharmacological Society.

Optimum design of structures subject to general periodic loads

NASA Technical Reports Server (NTRS)

Reiss, Robert; Qian, B.

1989-01-01

A simplified version of Icerman's problem regarding the design of structures subject to a single harmonic load is discussed. The nature of the restrictive conditions that must be placed on the design space in order to ensure an analytic optimum are discussed in detail. Icerman's problem is then extended to include multiple forcing functions with different driving frequencies. And the conditions that now must be placed upon the design space to ensure an analytic optimum are again discussed. An important finding is that all solutions to the optimality condition (analytic stationary design) are local optima, but the global optimum may well be non-analytic. The more general problem of distributing the fixed mass of a linear elastic structure subject to general periodic loads in order to minimize some measure of the steady state deflection is also considered. This response is explicitly expressed in terms of Green's functional and the abstract operators defining the structure. The optimality criterion is derived by differentiating the response with respect to the design parameters. The theory is applicable to finite element as well as distributed parameter models.

Utility of Intermediate-Delay Washout CT Images for Differentiation of Malignant and Benign Adrenal Lesions: A Multivariate Analysis.

PubMed

Ng, Chaan S; Altinmakas, Emre; Wei, Wei; Ghosh, Payel; Li, Xiao; Grubbs, Elizabeth G; Perrier, Nancy D; Lee, Jeffrey E; Prieto, Victor G; Hobbs, Brian P

2018-06-27

The objective of this study was to identify features that impact the diagnostic performance of intermediate-delay washout CT for distinguishing malignant from benign adrenal lesions. This retrospective study evaluated 127 pathologically proven adrenal lesions (82 malignant, 45 benign) in 126 patients who had undergone portal venous phase and intermediate-delay washout CT (1-3 minutes after portal venous phase) with or without unenhanced images. Unenhanced images were available for 103 lesions. Quantitatively, lesion CT attenuation on unenhanced (UA) and delayed (DL) images, absolute and relative percentage of enhancement washout (APEW and RPEW, respectively), descriptive CT features (lesion size, margin characteristics, heterogeneity or homogeneity, fat, calcification), patient demographics, and medical history were evaluated for association with lesion status using multiple logistic regression with stepwise model selection. Area under the ROC curve (A z ) was calculated from both univariate and multivariate analyses. The predictive diagnostic performance of multivariate evaluations was ascertained through cross-validation. A z for DL, APEW, RPEW, and UA was 0.751, 0.795, 0.829, and 0.839, respectively. Multivariate analyses yielded the following significant CT quantitative features and associated A z when combined: RPEW and DL (A z = 0.861) when unenhanced images were not available and APEW and UA (A z = 0.889) when unenhanced images were available. Patient demographics and presence of a prior malignancy were additional significant factors, increasing A z to 0.903 and 0.927, respectively. The combined predictive classifier, without and with UA available, yielded 85.7% and 87.3% accuracies with cross-validation, respectively. When appropriately combined with other CT features, washout derived from intermediate-delay CT with or without additional clinical data has potential utility in differentiating malignant from benign adrenal lesions.

Multiple breath washout analysis in infants: quality assessment and recommendations for improvement.

PubMed

Anagnostopoulou, Pinelopi; Egger, Barbara; Lurà, Marco; Usemann, Jakob; Schmidt, Anne; Gorlanova, Olga; Korten, Insa; Roos, Markus; Frey, Urs; Latzin, Philipp

2016-03-01

Infant multiple breath washout (MBW) testing serves as a primary outcome in clinical studies. However, it is still unknown whether current software algorithms allow between-centre comparisons. In this study of healthy infants, we quantified MBW measurement errors and tried to improve data quality by simply changing software settings. We analyzed best quality MBW measurements performed with an ultrasonic flowmeter in 24 infants from two centres in Switzerland with the current software settings. To challenge the robustness of these settings, we also used alternative analysis approaches. Using the current analysis software, the coefficient of variation (CV) for functional residual capacity (FRC) differed significantly between centres (mean  ±  SD (%): 9.8  ±  5.6 and 5.8  ±  2.9, respectively, p  =  0.039). In addition, FRC values calculated during the washout differed between  -25 and  +30% from those of the washin of the same tracing. Results were mainly influenced by analysis settings and temperature recordings. Changing few algorithms resulted in significantly more robust analysis. Non-systematic inter-centre differences can be reduced by using correctly recorded environmental data and simple changes in the software algorithms. We provide implications that greatly improve infant MBW outcomes' quality and can be applied when multicentre trials are conducted.

Pharmacokinetics of a Single Oral Dose of the MEK1/2 Inhibitor Selumetinib in Subjects With End‐Stage Renal Disease or Varying Degrees of Hepatic Impairment Compared With Healthy Subjects

PubMed Central

Dymond, Angela W.; Martin, Paul; Huang, Yifan; Severin, Paul; Holmes, Victoria; Mariani, Gabriella; Marbury, Thomas

2016-01-01

Abstract Two phase I open‐label studies were conducted to investigate the pharmacokinetics (PK), safety, and tolerability of single oral doses of selumetinib in subjects with end‐stage renal disease (ESRD) undergoing hemodialysis and subjects with varying degrees of hepatic impairment; both studies included a matched control group comprised of healthy individuals. In the renal impairment study, subjects received single doses of selumetinib 50 mg; those with ESRD received selumetinib before and after dialysis (with a between‐treatment washout period of ≥7 days). In the hepatic impairment study, subjects received varying single doses of selumetinib (20‐50 mg) depending on liver dysfunction (mild, moderate, or severe as per Child‐Pugh classification). PK, safety, and tolerability data were collected from both studies. Overall, 24 subjects were included in the renal impairment study (ESRD, N = 12; healthy subjects, N = 12). Selumetinib exposure (AUC and Cmax) was not increased in the ESRD group vs healthy subjects. Selumetinib exposure was lower when selumetinib was dosed before vs after dialysis, although individual exposure was variable. Overall, 32 subjects were included in the hepatic impairment study (mild, moderate, and severe impairment, N = 8 per group; healthy subjects, N = 8). Generally, dose‐normalized total selumetinib exposure was increased by 25% to 59% in subjects with moderate and severe hepatic impairment compared with healthy subjects. Increasing Child‐Pugh score, decreasing serum albumin, and increasing prothrombin time correlated with increasing unbound selumetinib exposure. In both studies, selumetinib was well tolerated with no new safety concerns. These studies will inform dose adjustment considerations in patients. PMID:28019010

Actual driving performance and psychomotor function in healthy subjects after acute and subchronic treatment with escitalopram, mirtazapine, and placebo: a crossover trial.

PubMed

Wingen, Marleen; Bothmer, John; Langer, Stefan; Ramaekers, Johannes G

2005-04-01

The effects of escitalopram 10 to 20 mg/day and mirtazapine 30 to 45 mg/day on actual driving and psychomotor performance of 18 healthy subjects were determined in a randomized, double-blind, placebo-controlled, multiple-dose, 3-way crossover trial. Each treatment period lasted for 15 days and was separated from the next period by a washout period of at least 13 days. Subjects received an evening dose of escitalopram 10 mg, mirtazapine 30 mg, or placebo from days 1 to 7 and an evening dose of escitalopram 20 mg, mirtazapine 45 mg, or placebo from days 8 to 15. On days 2, 9, and 16, reflecting acute period, dose increase, and steady state, respectively, the Road Tracking Test was performed. The main parameter was standard deviation of lateral position. Psychomotor performance was also assessed on days 2, 9, and 16 by laboratory computer tasks. Subjective sleep quality was measured with the Groninger Sleep Quality Scale, and mood was measured by visual analogue scales. Treatment differences were apparent during the acute treatment period, in which subjects treated with mirtazapine 30 mg performed less well on the driving test as compared to placebo. The Divided Attention Task results also revealed a significant increase in tracking error after a single dose of mirtazapine 30 mg as compared to placebo. Mirtazapine decreased feelings of alertness and contentedness. Mirtazapine did not affect performance on days 9 and 16 of treatment. Escitalopram did not affect driving, psychomotor performance, or subjective mood throughout treatment. Driving performance, as well as psychomotor functioning, was not affected by escitalopram treatment in healthy subjects. Driving performance was significantly impaired after ingestion of mirtazapine 30 mg during the acute treatment period.

Consumption of strawberries on a daily basis increases the non-urate 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging activity of fasting plasma in healthy subjects

PubMed Central

Prymont-Przyminska, Anna; Zwolinska, Anna; Sarniak, Agata; Wlodarczyk, Anna; Krol, Maciej; Nowak, Michal; de Graft-Johnson, Jeffrey; Padula, Gianluca; Bialasiewicz, Piotr; Markowski, Jaroslaw; Rutkowski, Krzysztof P.; Nowak, Dariusz

2014-01-01

Strawberries contain anthocyanins and ellagitanins which have antioxidant properties. We determined whether the consumption of strawberries increase the plasma antioxidant activity measured as the ability to decompose 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in healthy subjects. The study involved 10 volunteers (age 41 ± 6 years, body weight 74.4 ± 12.7 kg) that consumed 500 g of strawberries daily for 9 days and 7 matched controls. Fasting plasma and spot morning urine samples were collected at baseline, during fruit consumption and after a 6 day wash-out period. DPPH decomposition was measured in both deproteinized native plasma specimens and pretreated with uricase (non-urate plasma). Twelve phenolics were determined with HPLC. Strawberries had no effect on the antioxidant activity of native plasma and circulating phenolics. Non-urate plasma DPPH decomposition increased from 5.7 ± 0.6% to 6.6 ± 0.6%, 6.5 ± 1.0% and 6.3 ± 1.4% after 3, 6 and 9 days of supplementation, respectively. The wash-out period reversed this activity back to 5.7 ± 0.8% (p<0.01). Control subjects did not reveal any changes of plasma antioxidant activity. Significant increase in urinary urolithin A and 4-hydroxyhippuric (by 8.7- and 5.9-times after 6 days of supplementation with fruits) was noted. Strawberry consumption can increase the non-urate plasma antioxidant activity which, in turn, may decrease the risk of systemic oxidants overactivity. PMID:25120279

Acute Consumption of Resistant Starch Reduces Food Intake but Has No Effect on Appetite Ratings in Healthy Subjects.

PubMed

Ble-Castillo, Jorge L; Juárez-Rojop, Isela E; Tovilla-Zárate, Carlos A; García-Vázquez, Carlos; Servin-Cruz, Magda Z; Rodríguez-Hernández, Arturo; Araiza-Saldaña, Claudia I; Nolasco-Coleman, Ana M; Díaz-Zagoya, Juan C

2017-07-04

Previous studies have shown the benefits of native banana starch (NBS) supplementation in improving glucose metabolism and reducing body weight (BW) in humans. However, the effect of this starch on appetite regulation is unknown. The aim of this study was to examine the effects of NBS rich resistant starch on subjective measurements of appetite, energy intake, and appetite hormones in healthy subjects. Postprandial glucose and insulin responses were also assessed. In a randomized, single-blind, crossover study, 28 healthy young subjects consumed a beverage containing either 40 g of NBS or 40 g of digestible corn starch (DCS) on two separate occasions. Effects on appetite were estimated using visual analogue scales (VAS) and satiety hormone responses. At the end of the intervention, participants were provided with a pre-weighed ad libitum homogeneous test meal. After a washout period of 1 week, subjects received the alternative treatment. NBS supplementation induced a reduction in food intake, glucose area under the curve (AUC)-180 min, and insulin AUC-180 min. However, there was no associated effect on the subjective appetite ratings or gut hormones. NBS supplementation may help to reduce meal size and control BW.

Acute Consumption of Resistant Starch Reduces Food Intake but Has No Effect on Appetite Ratings in Healthy Subjects

PubMed Central

Ble-Castillo, Jorge L.; Juárez-Rojop, Isela E.; Tovilla-Zárate, Carlos A.; García-Vázquez, Carlos; Servin-Cruz, Magda Z.; Rodríguez-Hernández, Arturo; Araiza-Saldaña, Claudia I.; Nolasco-Coleman, Ana M.

2017-01-01

Previous studies have shown the benefits of native banana starch (NBS) supplementation in improving glucose metabolism and reducing body weight (BW) in humans. However, the effect of this starch on appetite regulation is unknown. The aim of this study was to examine the effects of NBS rich resistant starch on subjective measurements of appetite, energy intake, and appetite hormones in healthy subjects. Postprandial glucose and insulin responses were also assessed. In a randomized, single-blind, crossover study, 28 healthy young subjects consumed a beverage containing either 40 g of NBS or 40 g of digestible corn starch (DCS) on two separate occasions. Effects on appetite were estimated using visual analogue scales (VAS) and satiety hormone responses. At the end of the intervention, participants were provided with a pre-weighed ad libitum homogeneous test meal. After a washout period of 1 week, subjects received the alternative treatment. NBS supplementation induced a reduction in food intake, glucose area under the curve (AUC)-180 min, and insulin AUC-180 min. However, there was no associated effect on the subjective appetite ratings or gut hormones. NBS supplementation may help to reduce meal size and control BW. PMID:28677623

Bioavailability of two oral suspension and two oral tablet formulations of acyclovir 400 mg: two single-dose, open-label, randomized, two-period crossover comparisons in healthy Mexican adult subjects.

PubMed

Palma-Aguirre, Jose Antonio; Absalón-Reyes, Jose Antonio; Novoa-Heckel, Germán; de Lago, Alberto; Oliva, Iván; Rodríguez, Zulema; González-de la Parra, Mario; Burke-Fraga, Victoria; Namur, Salvador

2007-06-01

Acyclovir is an important antiviral drug, used extensively for treatment of herpes simplex and varicella zoster. Six oral generic formulations of acyclovir are available in Mexico; however, a literature search failed to identify data information concerning the bioavailability of these formulations in the Mexican population. The aim of these 2 studies was to compare the bioavailability of 4 oral formulations of acyclovir 400 mg--2 tablet formulations and 2 suspension formulations--with their corresponding listed drug references in Mexico (a list issued by Mexican Health Authorities). Two separate, single-dose, open-label, randomized, 2-period crossover studies were conducted at the Centro de Estudios Científicos y Clínicos Pharma, S.A. de C.V. (clinical unit), Mexico City, Mexico. For each study, a different set of eligible subjects were selected. They included healthy Mexican volunteers of either sex. For each study, subjects were randomly assigned to receive 1 test formulation of acyclovir 400 mg followed by the reference formulation, or vice versa, with a 1-week washout period between doses. After a 12-hour (overnight) fast, subjects received a single 400-mg dose (tablet or 10-mL suspension) of the corresponding formulation. For the analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, and 24 hours after dosing. The formulations were considered bioequivalent if the natural logarithm (ln)-transformed ratios of Cmax and AUC were within the predetermined equivalence range of 80% to 125% and if P subject interviews. Twenty-six subjects were enrolled in the study for the suspension dosage form and 25 completed it (13 men, 12 women; mean age, 22.2 years

Effect of red yeast rice combined with antioxidants on lipid pattern, hs-CRP level, and endothelial function in moderately hypercholesterolemic subjects.

PubMed

Cicero, Arrigo F G; Morbini, Martino; Parini, Angelo; Urso, Riccardo; Rosticci, Martina; Grandi, Elisa; Borghi, Claudio

2016-01-01

Our aim was to test, through a crossover, double-blind, placebo-controlled randomized clinical trial, if a short-term treatment with 10 mg monacolins combined with antioxidants could improve lipid pattern, high-sensitivity C-reactive protein (hs-CRP), and endothelial function in a small cohort of moderately hypercholesterolemic subjects. Thus, 25 healthy, moderately hypercholesterolemic subjects were consecutively enrolled and, after 4 weeks of stabilization diet, were randomized to the sequence placebo followed by a washout, monacolins or monacolins followed by a washout, placebo, with each period being 4 weeks long. At each study step, a complete lipid pattern, safety parameters, hs-CRP, and endothelial function have been measured. When compared to the placebo phase, during monacolin treatment, patients experienced a more favorable percentage change in total cholesterol (TC) (TC after monacolin treatment, -18.35%; TC after placebo treatment, -5.39%), low-density lipoprotein cholesterol (LDL-C) (LDL after monacolin treatment, -22.36%; LDL after placebo treatment, -1.38%), non-high-density lipoprotein cholesterol (HDL-C) (non-HDL after monacolin treatment, -22.83%; non-HDL after placebo treatment: -7.15%), hs-CRP (hs-CRP after monacolin treatment: -2.33%; hs-CRP after placebo treatment, 2.11%), and endothelial function (pulse volume displacement after monacolin treatment, 18.59%; pulse volume displacement after placebo treatment, -6.69%). No significant difference was observed with regard to triglycerides, HDL-cholesterol, and safety parameters. On the basis of our data, we could demonstrate that a 10 mg monacolin nutraceutical treatment appears to safely reduce cholesterolemia, hs-CRP, and markers of vascular remodeling in moderately hypercholesterolemic subjects. These results need to be confirmed in larger patient samples and in studies with longer duration.

Delafloxacin Pharmacokinetics in Subjects With Varying Degrees of Renal Function

PubMed Central

Hoover, Randall K.; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K.; Quintas, Megan

2017-01-01

Abstract Delafloxacin, a fluoroquinolone, has activity against gram‐positive organisms including methicillin‐resistant Staphylococcus aureus and fluoroquinolone‐susceptible and –resistant gram‐negative organisms. This study was conducted to determine delafloxacin pharmacokinetics after a single intravenous infusion or oral dose administration in subjects with varying degrees of renal function. The study was an open‐label, parallel‐group crossover study in subjects with normal renal function or with mild, moderate, or severe renal impairment. Subjects received 300 mg delafloxacin intravenously, placebo intravenously, and 400 mg delafloxacin orally in 3 periods separated by ≥14‐day washouts. Blood and urine pharmacokinetic parameters were calculated using noncompartmental methods. Delafloxacin total clearance decreased with decreasing renal function, with a corresponding increase in AUC0–∞. After intravenous administration, mean total clearance was 13.7 and 7.07 L/h, and mean AUC0–∞ was 22.6 and 45.0 μg·h/mL in normal and severe renal subjects, respectively. Mean renal clearance as determined by urinary excretion was 6.03 and 0.44 L/h in normal and severe renal impairment subjects, respectively. Total clearance exhibited linear relationships to eGFR and CLCR. Similar observations were found after oral administration of delafloxacin. Single doses of delafloxacin 300 mg intravenously and 400 mg orally were well tolerated in all groups. In conclusion, renal insufficiency has an effect on delafloxacin clearance; a dosing adjustment for intravenous dosing is warranted for patients with severe renal impairment (eGFR < 30 mL/min). PMID:29251785

Optical spectroscopy of the bladder washout fluid to optimize fluorescence cystoscopy with Hexvix®.

PubMed

Martoccia, Carla; Zellweger, Matthieu; Lovisa, Blaise; Jichlinski, Patrice; van den Bergh, Hubert; Wagnières, Georges

2014-09-01

Fluorescence cystoscopy enhances detection of early bladder cancer. Water used to inflate thebladder during the procedure rapidly contains urine, which may contain fluorochromes. This frequently degradesfluorescence images. Samples of bladder washout fluid (BWF) or urine were collected (15 subjects). We studiedtheir fluorescence properties and assessed changes induced by pH (4 to 9) and temperature (15°C to 41°C).A typical fluorescence spectrum of BWF features a main peak (excitation/emission: 320∕420 nm, FWHM =50∕100 nm) and a weaker (5% to 20% of main peak intensity), secondary peak (excitation/emission: 455∕525 nm, FWHM = 80∕50 nm). Interpatient fluctuations of fluorescence intensity are observed. Fluorescence intensity decreases when temperature increases (max 30%) or pH values vary (max 25%). Neither approach is compatible with clinical settings. Fluorescence lifetime measurements suggest that 4-pyridoxic acid/riboflavin is the most likely molecule responsible for urine’s main/secondary fluorescence peak. Our measurements give an insight into the spectroscopy of the detrimental background fluorescence. This should be included in the optical design of fluorescence cystoscopes. We estimate that restricting the excitation range from 370–430 nm to 395–415 nm would reduce the BWF background by a factor 2.

Computationally-efficient optical coherence elastography to assess degenerative osteoarthritis based on ultrasound-induced fringe washout (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tong, Minh Q.; Hasan, M. Monirul; Gregory, Patrick D.; Shah, Jasmine; Park, B. Hyle; Hirota, Koji; Liu, Junze; Choi, Andy; Low, Karen; Nam, Jin

2017-02-01

We demonstrate a computationally-efficient optical coherence elastography (OCE) method based on fringe washout. By introducing ultrasound in alternating depth profile, we can obtain information on the mechanical properties of a sample within acquisition of a single image. This can be achieved by simply comparing the intensity in adjacent depth profiles in order to quantify the degree of fringe washout. Phantom agar samples with various densities were measured and quantified by our OCE technique, the correlation to Young's modulus measurement by atomic force micrscopy (AFM) were observed. Knee cartilage samples of monoiodo acetate-induced arthiritis (MIA) rat models were utilized to replicate cartilage damages where our proposed OCE technique along with intensity and birefringence analyses and AFM measurements were applied. The results indicate that our OCE technique shows a correlation to the techniques as polarization-sensitive OCT, AFM Young's modulus measurements and histology were promising. Our OCE is applicable to any of existing OCT systems and demonstrated to be computationally-efficient.

Insulin absorption and subcutaneous blood flow in normal subjects during insulin-induced hypoglycemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernqvist-Forbes, E.; Linde, B.; Gunnarsson, R.

1988-09-01

We studied the effects of insulin-induced hypoglycemia on the absorption of 10 U /sup 125/I-labeled soluble human insulin injected sc in the thigh in 10 normal subjects. The disappearance of /sup 125/I from the injection site was followed by external gamma-counting. Subcutaneous blood flow (ATBF) was measured concomitantly with the 133Xe washout technique. The plasma glucose nadir (mean, 2.0 +/- 0.1 (+/- SE) mmol/L) occurred at 33 +/- 3 min and resulted in maximal arterial plasma epinephrine concentrations of approximately 6 nmol/L. From 30 min before to 60 min after the glucose nadir the (/sup 125/I)insulin absorption rate was depressedmore » compared to that during normoglycemia. The first order disappearance rate constants were reduced by approximately 50% (P less than 0.01) during the first 30-min interval after the glucose nadir. During the same period ATBF increased by 100% (P less than 0.05). The results suggest that in normal subjects the absorption of soluble insulin from a sc depot is depressed in connection with hypoglycemia, despite considerably elevated ATBF.« less

Strong washout approximation to resonant leptogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garbrecht, Björn; Gautier, Florian; Klaric, Juraj, E-mail: garbrecht@tum.de, E-mail: florian.gautier@tum.de, E-mail: juraj.klaric@tum.de

We show that the effective decay asymmetry for resonant Leptogenesis in the strong washout regime with two sterile neutrinos and a single active flavour can in wide regions of parameter space be approximated by its late-time limit ε=Xsin(2φ)/(X{sup 2}+sin{sup 2}φ), where X=8πΔ/(|Y{sub 1}|{sup 2}+|Y{sub 2}|{sup 2}), Δ=4(M{sub 1}-M{sub 2})/(M{sub 1}+M{sub 2}), φ=arg(Y{sub 2}/Y{sub 1}), and M{sub 1,2}, Y{sub 1,2} are the masses and Yukawa couplings of the sterile neutrinos. This approximation in particular extends to parametric regions where |Y{sub 1,2}|{sup 2}>> Δ, i.e. where the width dominates the mass splitting. We generalise the formula for the effective decay asymmetry to themore » case of several flavours of active leptons and demonstrate how this quantity can be used to calculate the lepton asymmetry for phenomenological scenarios that are in agreement with the observed neutrino oscillations. We establish analytic criteria for the validity of the late-time approximation for the decay asymmetry and compare these with numerical results that are obtained by solving for the mixing and the oscillations of the sterile neutrinos. For phenomenologically viable models with two sterile neutrinos, we find that the flavoured effective late-time decay asymmetry can be applied throughout parameter space.« less

Wash-in and wash-out curves of sevoflurane and isoflurane in morbidly obese patients.

PubMed

Torri, G; Casati, A; Comotti, L; Bignami, E; Santorsola, R; Scarioni, M

2002-06-01

5th to the 30th min. Also the washout curve was faster in the sevoflurane group during the observation period; however, the observed differences were statistically significant only 30 and 60 sec after discontinuation of the inhalational agents. The results of this prospective, randomized study confirmed that sevoflurane provides more rapid wash-in and wash-out curves than isoflurane also in the morbid obese patient.

Training in multiple breath washout testing for respiratory physiotherapists.

PubMed

O'Neill, Katherine; Elborn, J Stuart; Tunney, Michael M; O'Neill, Philip; Rowan, Stephen; Martin, Susan; Bradley, Judy M

2018-03-01

The development of multiple breath washout (MBW) testing in respiratory disease highlights the need for increased awareness amongst respiratory physiotherapists and a potential opportunity for professional development in the use of an important outcome measure for clinical trials. To rationalise how MBW may be a useful assessment tool for respiratory physiotherapists and to describe a local MBW training and certification programme for physiotherapists. The respiratory Multidisciplinary Team in the Belfast Health and Social Care Trust (BHSCT) identified a need for MBW testing to be available to facilitate clinical research and assessment. A 2day training programme consisting of prereading preparation, self-directed learning, theory presentations, practical demonstrations and hands-on practice was developed and delivered. All participants underwent a certification process. We have demonstrated the successful training and certification of clinical and research physiotherapists and encourage other respiratory physiotherapists to consider MBW test training. Copyright © 2017 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Subjects with impaired fasting glucose: evolution in a period of 6 years.

PubMed

Leiva, E; Mujica, V; Orrego, R; Wehinger, S; Soto, A; Icaza, G; Vásquez, M; Díaz, L; Andrews, M; Arredondo, M

2014-01-01

To study the evolution of impaired fasting glucose (IFG), considering glucose and HbA1c levels and risk factors associated, in a period of 6 years. We studied 94 subjects with impaired fasting glucose (IFG) that were diagnosed in 2005 and followed up to 2012. Glucose and HbA1c levels were determined. A descriptive analysis of contingence charts was performed in order to study the evolution in the development of type-2 diabetes mellitus (T2DM). Twenty-eight of ninety-four subjects became T2DM; 51/94 remained with IFG; and 20/94 presented normal fasting glucose. From the 28 diabetic subjects, 9 had already developed diabetes and were under treatment with oral hypoglycemic agents; 5 were diagnosed with plasma glucose < 126 mg/dL, but with HbA1c over 6.5%. In those who developed diabetes, 15/28 had a family history of T2DM in first relative degree. Also, diabetic subjects had a BMI significantly higher than nodiabetics (t test: P < 0.01). The individuals that in 2005 had the highest BMI are those who currently have diabetes. The IFG constitutes a condition of high risk of developing T2DM in a few years, especially over 110 mg/dL and in obesity patients.

Subjects with Impaired Fasting Glucose: Evolution in a Period of 6 Years

PubMed Central

Leiva, E.; Mujica, V.; Orrego, R.; Wehinger, S.; Soto, A.; Icaza, G.; Vásquez, M.; Díaz, L.; Andrews, M.; Arredondo, M.

2014-01-01

Aim. To study the evolution of impaired fasting glucose (IFG), considering glucose and HbA1c levels and risk factors associated, in a period of 6 years. Methods. We studied 94 subjects with impaired fasting glucose (IFG) that were diagnosed in 2005 and followed up to 2012. Glucose and HbA1c levels were determined. A descriptive analysis of contingence charts was performed in order to study the evolution in the development of type-2 diabetes mellitus (T2DM). Results. Twenty-eight of ninety-four subjects became T2DM; 51/94 remained with IFG; and 20/94 presented normal fasting glucose. From the 28 diabetic subjects, 9 had already developed diabetes and were under treatment with oral hypoglycemic agents; 5 were diagnosed with plasma glucose < 126 mg/dL, but with HbA1c over 6.5%. In those who developed diabetes, 15/28 had a family history of T2DM in first relative degree. Also, diabetic subjects had a BMI significantly higher than nodiabetics (t test: P < 0.01). The individuals that in 2005 had the highest BMI are those who currently have diabetes. Conclusion. The IFG constitutes a condition of high risk of developing T2DM in a few years, especially over 110 mg/dL and in obesity patients. PMID:25215305

Novel methodology to perform sulfur hexafluoride (SF6)-based multiple-breath wash-in and washout in infants using current commercially available equipment.

PubMed

Gustafsson, P M; Robinson, P D; Lindblad, A; Oberli, D

2016-11-01

Multiple-breath inert gas washout (MBW) is ideally suited for early detection and monitoring of serious lung disease, such as cystic fibrosis, in infants and young children. Validated commercial options for the MBW technique are limited, and suitability of nitrogen (N 2 )-based MBW is of concern given the detrimental effect of exposure to pure O 2 on infant breathing pattern. We propose novel methodology using commercially available N 2 MBW equipment to facilitate 4% sulfur hexafluoride (SF 6 ) multiple-breath inert gas wash-in and washout suitable for the infant age range. CO 2 , O 2 , and sidestream molar mass sensor signals were used to accurately calculate SF 6 concentrations. An improved dynamic method for synchronization of gas and respiratory flow was developed to take into account variations in sidestream sample flow during MBW measurement. In vitro validation of triplicate functional residual capacity (FRC) assessments was undertaken under dry ambient conditions using lung models ranging from 90 to 267 ml, with tidal volumes of 28-79 ml, and respiratory rates 20-60 per minute. The relative mean (SD, 95% confidence interval) error of triplicate FRC determinations by washout was -0.26 (1.84, -3.86 to +3.35)% and by wash-in was 0.57 (2.66, -4.66 to +5.79)%. The standard deviations [mean (SD)] of percentage error among FRC triplicates were 1.40 (1.14) and 1.38 (1.32) for washout and wash-in, respectively. The novel methodology presented achieved FRC accuracy as outlined by current MBW consensus recommendations (95% of measurements within 5% accuracy). Further clinical evaluation is required, but this new technique, using existing commercially available equipment, has exciting potential for research and clinical use. Copyright © 2016 the American Physiological Society.

[Development of a Computer-aided Diagnosis System to Distinguish between Benign and Malignant Mammary Tumors in Dynamic Magnetic Resonance Images: Automatic Detection of the Position with the Strongest Washout Effect in the Tumor].

PubMed

Miyazaki, Yoshiaki; Tabata, Nobuyuki; Taroura, Tomomi; Shinozaki, Kenji; Kubo, Yuichiro; Tokunaga, Eriko; Taguchi, Kenichi

We propose a computer-aided diagnostic (CAD) system that uses time-intensity curves to distinguish between benign and malignant mammary tumors. Many malignant tumors show a washout pattern in time-intensity curves. Therefore, we designed a program that automatically detects the position with the strongest washout effect using the technique, such as the subtraction technique, which extracts only the washout area in the tumor, and by scanning data in 2×2 pixel region of interest (ROI). Operation of this independently developed program was verified using a phantom system that simulated tumors. In three cases of malignant tumors, the washout pattern detection rate in images with manually set ROI was ≤6%, whereas the detection rate with our novel method was 100%. In one case of a benign tumor, when the same method was used, we checked that there was no washout effect and detected the persistent pattern. Thus, the distinction between benign and malignant tumors using our method was completely consistent with the pathological diagnoses made. Our novel method is therefore effective for differentiating between benign and malignant mammary tumors in dynamic magnetic resonance images.

Comparison of Pharmacokinetics and Safety of a Fixed-dose Combination of Rosuvastatin and Ezetimibe Versus Separate Tablets in Healthy Subjects.

PubMed

Min, Kyoung Lok; Park, Min Soo; Jung, Jina; Chang, Min Jung; Kim, Choon Ok

2017-09-01

Rosuvastatin and ezetimibe are concomitantly used for dyslipidemia treatment. Compared with separate tablets, fixed-dose combination (FDC) tablets of rosuvastatin/ezetimibe could increase patient compliance. The aim of this study was to compare the pharmacokinetic (PK) profiles of an FDC tablet of rosuvastatin/ezetimibe and co-administration of rosuvastatin and ezetimibe as separate tablets in healthy Korean volunteers. This trial was a randomized, open-label, single-dose, 2-way crossover study. The healthy subjects received an FDC tablet of rosuvastatin 20 mg/ezetimibe 10 mg (test) or co-administration of rosuvastatin 20 mg and ezetimibe 10 mg (reference) in each period (periods 1 and 2), with a 14-day washout period. The blood samples for PK analysis were collected predose and up to 96 hours after administration, and safety was assessed throughout the study. Sixty-four healthy Korean subjects were enrolled, and 57 subjects completed the study. All subjects were men and mean age was 28.52 ± 5.93. The geometric least squares mean ratios (test/reference) and 90% CIs of C max and AUC 0-last were 101.54% (94.03-109.65) and 97.71% (91.86-103.93) for rosuvastatin, 108.93% (98.55-120.40) and 102.90% (96.72-109.47) for free ezetimibe, and 106.74% (98.18-116.05) and 104.24 % (99.53-109.17) for total ezetimibe. Twenty-four adverse events (AEs) were reported in 22 subjects. Three cases were related to the study drugs; 2 cases were mild, and 1 case was severe. However, all AEs were resolved without any sequelae. In addition, there were no serious AEs throughout the study. The FDC tablet of rosuvastatin/ezetimibe was well tolerated and resulted in comparable systemic exposure with co-administration of rosuvastatin and ezetimibe. ClinicalTrials.gov identifier: NCT02941848. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Utilizing a Suited Manikin Test Apparatus and Spacesuit Ventilation Loop to Evaluate Carbon Dioxide Washout

NASA Technical Reports Server (NTRS)

Chullen, Cinda; Conger, Bruce; Korona, Adam; Kanne, Bryan; McMillin, Summer; Norcross, Jason; Jeng, Frank; Swickrath, Mike

2014-01-01

NASA is pursuing technology development of an Advanced Extravehicular Mobility Unit (AEMU) which is an integrated assembly made up of primarily a pressure garment system and a Portable Life Support System (PLSS). The PLSS is further composed of an oxygen subsystem, a ventilation subsystem, and a thermal subsystem. One of the key functions of the ventilation system is to remove and control the carbon dioxide delivered to the crewmember. Carbon dioxide washout is the mechanism by which CO2 levels are controlled within the spacesuit helmet to limit the concentration of CO2 inhaled by the crew member. CO2 washout performance is a critical parameter needed to ensure proper and robust designs that are insensitive to human variabilities in a spacesuit. A Suited Manikin Test Apparatus (SMTA) is being developed to augment testing of the PLSS ventilation loop in order to provide a lower cost and more controlled alternative to human testing. The CO2 removal function is performed by the regenerative Rapid Cycle Amine (RCA) within the PLSS ventilation loop and its performance is evaluated within the integrated SMTA and Ventilation Loop test system. This paper will provide a detailed description of the schematics, test configurations, and hardware components of this integrated system. Results and analysis of testing performed with this integrated system will be presented within this paper.

Ventilation Inception and Washout, Scaling, and Effects on Hydrodynamic Performance of a Surface Piercing Strut

NASA Astrophysics Data System (ADS)

Harwood, Casey; Young, Yin Lu; Ceccio, Steven

2014-11-01

High-lift devices that operate at or near a fluid free surface (such as surface-piercing or shallowly-submerged propellers and hydrofoils) are prone to a multiphase flow phenomenon called ventilation, wherein non-condensable gas is entrained in the low-pressure flow, forming a cavity around the body and dramatically altering the global hydrodynamic forces. Experiments are being conducted at the University of Michigan's towing tank using a canonical surface-piercing strut to investigate atmospheric ventilation. The goals of the work are (i) to gain an understanding of the dominant physics in fully wetted, partially ventilated, and fully ventilated flow regimes, (ii) to quantify the effects of governing dimensionless parameters on the transition between flow regimes, and (iii) to develop scaling relations for the transition between flow regimes. Using theoretical arguments and flow visualization techniques, new criteria are developed for classifying flow regimes and transition mechanisms. Unsteady transition mechanisms are described and mapped as functions of the governing non-dimensional parameters. A theoretical scaling relationship is developed for ventilation washout, which is shown to adequately capture the experimentally-observed washout boundary. This material is based upon work supported by the National Science Foundation Graduate Student Research Fellowship under Grant No. DGE 1256260. Support also comes from the Naval Engineering Education Center (Award No. N65540-10-C-003).

99 mTc-MIBI washout as a complementary factor in the evaluation of idiopathic dilated cardiomyopathy (IDCM) using myocardial perfusion imaging.

PubMed

Shiroodi, Mohammad Kazem; Shafiei, Babak; Baharfard, Nastaran; Gheidari, Mohammad Esmail; Nazari, Babak; Pirayesh, Elaheh; Kiasat, Ali; Hoseinzadeh, Samaneh; Hashemi, Abolghassem; Akbarzadeh, Mohammad Ali; Javadi, Hamid; Nabipour, Iraj; Assadi, Majid

2012-01-01

Rapid technetium-99 m methoxyisobutylisonitrile (99 mTc-MIBI) washout has been shown to occur in impaired myocardia. This study is based on the hypothesis that scintigraphy can be applied to calculate the myocardial 99 mTc-MIBI washout rate (WR) to diagnose and evaluate heart failure severity and other left ventricular functional parameters specifically in idiopathic dilated cardiomyopathy (IDCM) patients. Patients with IDCMP (n = 17; 52.65 ± 11.47 years) and normal subjects (n = 6; 49.67 ± 10.15 years) were intravenously administered 99 mTc-hexakis-2-methoxyisobutylisonitrile (99 mTc-MIBI). Next, early and delayed planar data were acquired (at 3.5-h intervals), and electrocardiogram (ECG)-gated myocardial perfusion single photon emission computed tomography (SPECT) was performed. The 99 mTc-MIBI WR was calculated using early and delayed planar images. Left ventricular functional parameters were also analyzed using quantitative gated SPECT (QGS) data. In target group, myocardial WRs (29.13 ± 6.68%) were significantly higher than those of control subjects (14.17 ± 3.31%; P < 0.001). The 99 mTc-MIBI WR increased with the increasing severity of the NYHA functional class (23.16 ± 1.72% for class I, 30.25 ± 0.95% for class II, 32.60 ± 6.73% for class III, and 37.50 ± 7.77% for class IV; P = 0.02). The WR was positively correlated with the end-diastolic volume (EDV) index (r (2) = 0.216; β = 0.464; P = 0.02 [ml/m(2)], the end-systolic volume (ESV) index (r (2) = 0.234; β = 0.484; P = 0.01 [ml/m(2)]), the summed motion score (SMS) (r (2) = 0.544; β = 0.738; P = 0.00), and the summed thickening score (STS) (r (2) = 0.656; β = 0.810; P = 0.00); it was negatively correlated with the left ventricular ejection fraction (LVEF) (r (2) = 0.679; β = -0.824; P = 0.00). It can be concluded that 99 mTc-MIBI scintigraphy might be a valuable molecular imaging tool for the diagnosis and evaluation of myocardial damage or dysfunction severity.

A Novel Physiological Investigation of the Functional Residual Capacity by the Bias Flow Nitrogen Washout Technique in Infants

PubMed Central

Morris, Mohy G.

2011-01-01

Summary The dynamic functional residual capacity (FRCdyn), the lung volume most routinely measured in infants, is an unreliable volume landmark. In addition to the FRCdyn, we measured the (passive) static FRC (FRCst) by inducing a brief post-hyperventilation apnea (PHA) in 33 healthy infants aged 7.4–127.2 weeks. A commercial system for nitrogen (N2) washout to measure FRC, and a custom made system to monitor and record flow and airwayopening pressure signals in real-time were used in unison. Infants were manually hyperventilated to induce a PHA. After the last passive expiration, FRCst was estimated by measuring the volume of N2 expired after end-passive expiratory switching of the inspired gas from room air to 100% oxygen during the post-expiratory apneic pause. Repeatable intrasubject FRCst and FRCdyn measurements overlapped in most infants including the younger ones (P = 0.2839). Mean (95% confidence interval [CI]) FRCst was 21.1 (20.0–22.3), and error-corrected FRCdyn was 21.4 (20.4–22.4) ml/kg. Mean (washout time [t]) tFRCst was longer than tFRCdyn 60 sec (95% CI 55–65) versus 47 sec (95% CI 43–51) (P<0.0001). The FRC and washout time were dependent on body length, weight and age. We conclude that the FRCst is not different from the FRCdyn in infants. The FRCst is a reliable volume landmark because the PHA stabilizes the end-expiratory level by potentially abolishing the sedated infant’s breathing strategies. The FRCst lacks potential sources of errors and disadvantages associated with measuring the FRCdyn. The findings cast significant doubt on the traditional physiology of air trapping in healthy infants’ lungs. PMID:19499588

Effect of consuming a purple-fleshed sweet potato beverage on health-related biomarkers and safety parameters in Caucasian subjects with elevated levels of blood pressure and liver function biomarkers: a 4-week, open-label, non-comparative trial

PubMed Central

OKI, Tomoyuki; KANO, Mitsuyoshi; WATANABE, Osamu; GOTO, Kazuhisa; BOELSMA, Esther; ISHIKAWA, Fumiyasu; SUDA, Ikuo

2016-01-01

An open-label study with one treatment arm was conducted to investigate changes in health-related biomarkers (blood pressure and liver enzyme activity) and the safety of 4 weeks of consuming a purple-fleshed sweet potato beverage in Caucasian subjects. Twenty healthy adults, 18–70 years of age, with a body mass index >25 kg/m2, elevated blood pressure and elevated levels of liver function biomarkers consumed two cartons of purple-fleshed sweet potato beverage (125 ml, including 117 mg anthocyanin per carton) daily for 4 weeks. Hematology, serum clinical profile, dipstick urinalysis and blood pressure were determined before consumption, at 2 and 4 weeks of consumption and after a 2-week washout period. A trend was found toward lowering systolic blood pressure during the treatment period (p=0.0590). No significant changes were found in diastolic blood pressure throughout the study period. Systolic blood pressure was significantly lower after 4 weeks of consumption compared with before consumption (p=0.0125) and was significantly higher after the 2-week washout period compared with after consumption (p=0.0496). The serum alanine aminotransferase level significantly increased over time, but aspartate aminotransferase and γ-glutamyltransferase levels stayed within the normal range of reference values. Safety parameters of the blood and urine showed no clinically relevant changes. The consumption of a purple-fleshed sweet potato beverage for 4 weeks resulted in no clinically relevant changes in safety parameters of the blood and urine and showed a trend toward lowering systolic blood pressure. PMID:27508114

Two Formulations of Venlafaxine are Bioequivalent when Administered as Open Capsule Mixed with Applesauce to Healthy Subjects.

PubMed

Jain, Renu T; Panda, J; Srivastava, A

2011-09-01

Venlafaxine is a unique antidepressant approved for treatment of various depressive disorders. A single dose, cross-over bioequivalence study was performed with two different formulations of venlafaxine 150 mg extended-release capsules in which the contents of capsule were mixed with applesauce and administered to healthy subjects under fed condition. A total of 24 healthy adult male subjects participated in this randomized, single-dose, non-blinded, two-way crossover study conducted at a single centre and 23 subjects completed the study as per the study protocol. After an overnight fast of 10 h, a high-fat and high-calorie breakfast was served 30 min before dosing. The subjects then received a single dose of either formulation administered with apple sauce followed by 240 ml of water as per randomized schedule in each period separated by a washout period of 7 days. A series of blood samples were collected upto 72 h for estimation of venlafaxine and its active metabolite, O-desmethylvenlafaxine. The quantification of venlafaxine and O-desmethylvenlafaxine was done by LC-MS/MS method and pharmacokinetic and statistical analysis by WinNonlin(®) 5.2 and SAS(®) 9.1.3. The results of the study demonstrated bioequivalence of two formulations as the 90% confidence interval for the intra-individual mean ratio of log-transformed C(max), AUC(0-t) and AUC(0-inf) of the test to the reference formulation were found within the defined bioequivalence range of 80.00%-125.00%. Both the formulations were well tolerated. This alternative mode of administration may provide benefits to patients who have difficulty in swallowing the capsule as a whole.

Two Formulations of Venlafaxine are Bioequivalent when Administered as Open Capsule Mixed with Applesauce to Healthy Subjects

PubMed Central

Jain, Renu T.; Panda, J.; Srivastava, A.

2011-01-01

Venlafaxine is a unique antidepressant approved for treatment of various depressive disorders. A single dose, cross-over bioequivalence study was performed with two different formulations of venlafaxine 150 mg extended-release capsules in which the contents of capsule were mixed with applesauce and administered to healthy subjects under fed condition. A total of 24 healthy adult male subjects participated in this randomized, single-dose, non-blinded, two-way crossover study conducted at a single centre and 23 subjects completed the study as per the study protocol. After an overnight fast of 10 h, a high-fat and high-calorie breakfast was served 30 min before dosing. The subjects then received a single dose of either formulation administered with apple sauce followed by 240 ml of water as per randomized schedule in each period separated by a washout period of 7 days. A series of blood samples were collected upto 72 h for estimation of venlafaxine and its active metabolite, O-desmethylvenlafaxine. The quantification of venlafaxine and O-desmethylvenlafaxine was done by LC-MS/MS method and pharmacokinetic and statistical analysis by WinNonlin® 5.2 and SAS® 9.1.3. The results of the study demonstrated bioequivalence of two formulations as the 90% confidence interval for the intra-individual mean ratio of log-transformed Cmax, AUC0-t and AUC0-inf of the test to the reference formulation were found within the defined bioequivalence range of 80.00%-125.00%. Both the formulations were well tolerated. This alternative mode of administration may provide benefits to patients who have difficulty in swallowing the capsule as a whole. PMID:22923863

Determination of rifaximin treatment period according to lactulose breath test values in nonconstipated irritable bowel syndrome subjects.

PubMed

Bae, Suhyun; Lee, Kwang Jae; Kim, Young-Sang; Kim, Kyu-Nam

2015-06-01

Small intestinal bacterial overgrowth (SIBO) can partly explain irritable bowel syndrome (IBS), and rifaximin has been observed to improve abdominal symptoms in nonconstipated IBS patients. However, there are few reports on the association of the rifaximin treatment periods with the results of a lactulose breath test (LBT). Therefore, we performed a retrospective review of patient charts to investigate the relation between the rifaximin treatment periods with LBT results in nonconstipated IBS patients. We also evaluated the time to achieve a symptomatic improvement in the IBS patients as compared to the changes in the LBT. We reviewed the charts for patients who showed IBS symptoms with documented positive results for LBT during their initial visit and who had a follow-up LBT after treatment with rifaximin. The LBT values were compared to the subjects' symptom scores. A total of 102 subjects had a follow-up LBT to assess LBT normalization. The subjects were divided into groups according to treatment periods of 4 weeks (n = 36), 8 weeks (n = 43), and 12 weeks (n = 23). The groups with a longer treatment exhibited an increase in the hydrogen gas value at 90 min and its sum during 90 min at the initial LBT. There were significant differences in hydrogen gas value at 90 min and in its sum during 90 min at the initial LBT between the groups treated for 4 and 12 weeks. The most significant treatment response was observed during the first 4 weeks for all treatment groups. Symptomatic improvement occurred earlier than LBT normalization in the treatment period over 4 weeks. The results indicate that different rifaximin treatment periods are needed in accordance with LBT levels to effectively eradicate SIBO.

Pharmacokinetics of Caffeine following a Single Administration of Coffee Enema versus Oral Coffee Consumption in Healthy Male Subjects

PubMed Central

Tosri, Nisanuch; Rojanasthien, Noppamas; Srichairatanakool, Somdet; Sangdee, Chaichan

2013-01-01

The objective of this study was to determine the pharmacokinetics of caffeine after single administration of a coffee enema versus coffee consumed orally in healthy male subjects. The study design was an open-label, randomized two-phase crossover study. Eleven healthy subjects were randomly assigned either to receive 500 mL of coffee enema for 10 minutes or to consume 180 mL of ready-to-drink coffee beverage. After a washout period of at least 10 days, all the subjects were switched to receive the alternate coffee procedure. Blood samples were collected immediately before and at specific time points until 12 hours after coffee administration in each phase. The mean caffeine content in both the coffee solution prepared for the coffee enema and the ready-to-drink coffee beverage was not statistically different. The C max and AUC of caffeine obtained from the coffee enema were about 3.5 times significantly less than those of the coffee consumed orally, despite having slightly but statistically faster T max. The t 1/2 of caffeine obtained following both coffee procedures did not statistically differ. In summary, the relative bioavailability of caffeine obtained from the coffee enema was about 3.5 times significantly less than those of the coffee consumed orally. PMID:23533801

Influence of cilazapril on memory functions and sleep behaviour in comparison with metoprolol and placebo in healthy subjects

PubMed Central

Dietrich, B.; Herrmann, W. M.

1989-01-01

1 In a controlled, randomized, double-blind study the influence of cilazapril and metoprolol on learning and memory functions and on sleep behaviour was investigated in healthy young volunteers under steady-state conditions. Twenty-three subjects were given either 2.5 mg cilazapril, 200 mg metoprolol, or placebo for 14 days in a latin square design separated by washout periods of 7 days. 2 To test memory functions different modalities—verbal, visual, numerical associative and two dimensional spatial memory were tested for recent anterograde recall, both short-term (less than 10 s) and middle-term (up to 15 min) were selected. The test had a content similar to that used in daily life situations. The sleep behaviour was tested both by objective (all night sleep EEG) and subjective measures. 3 Neither antihypertensive drug had an observable influence on memory performance at the dosages used under steady-state conditions. However, sleep was disturbed during metoprolol, while cilazapril could not be differentiated from placebo. The effects of metoprolol on sleep behaviour were observed in the objective and subjective measures. There was more frequent awakening during the night with the subjective complaint of difficulties in sleeping through. 4 From this study it is concluded that cilazapril has no major effect on memory functions and sleep behaviour. This is only true for the dosages given and under steady-state conditions. PMID:2527538

Influence of cilazapril on memory functions and sleep behaviour in comparison with metoprolol and placebo in healthy subjects.

PubMed

Dietrich, B; Herrmann, W M

1989-01-01

1. In a controlled, randomized, double-blind study the influence of cilazapril and metoprolol on learning and memory functions and on sleep behaviour was investigated in healthy young volunteers under steady-state conditions. Twenty-three subjects were given either 2.5 mg cilazapril, 200 mg metoprolol, or placebo for 14 days in a latin square design separated by washout periods of 7 days. 2. To test memory functions different modalities--verbal, visual, numerical associative and two dimensional spatial memory were tested for recent anterograde recall, both short-term (less than 10 s) and middle-term (up to 15 min) were selected. The test had a content similar to that used in daily life situations. The sleep behaviour was tested both by objective (all night sleep EEG) and subjective measures. 3. Neither antihypertensive drug had an observable influence on memory performance at the dosages used under steady-state conditions. However, sleep was disturbed during metoprolol, while cilazapril could not be differentiated from placebo. The effects of metoprolol on sleep behaviour were observed in the objective and subjective measures. There was more frequent awakening during the night with the subjective complaint of difficulties in sleeping through. 4. From this study it is concluded that cilazapril has no major effect on memory functions and sleep behaviour. This is only true for the dosages given and under steady-state conditions.

Comparison of heliox and oxygen as washing gases for the nitrogen washout technique in preterm infants.

PubMed

Poets, C F; Rau, G A; Gappa, M; Seidenberg, J

1996-06-01

The nitrogen washout technique usually involves exposure of the patient to 100% oxygen for several minutes. This may be dangerous in preterm infants who are at risk of retinopathy of prematurity (ROP). We wanted to know whether heliox (79% He, 21% O2) can be used instead of oxygen when determining functional residual capacity (FRC). FRC measurements were made in 14 preterm infants [median (range) gestational age at birth 34 wk (27-37 wk), and at time of study 36 wk (33-40 wk)] who were breathing room air. FRC was measured using a computerized infant pulmonary function system, beginning in random order with either 100% O2 followed by heliox or vice versa. There was no systematic difference between the two methods with regard to lung volume measurements: mean (SD) FRC values, corrected for body weight, were 22.9 (7.1) mL/kg for O2 and 23.4 (7.0) mL/kg for heliox. We did not observe a systematic influence of the type of washing gas used (heliox or oxygen) on FRC in these infants. Our results suggest that the use of heliox instead of pure oxygen may be a suitable and safer alternative for FRC measurements with the nitrogen washout technique in preterm infants who are breathing low concentrations of inspired oxygen and are still at risk of ROP.

Utilizing a Suited Manikin Test Apparatus and Space Suit Ventilation Loop to Evaluate Carbon Dioxide Washout

NASA Technical Reports Server (NTRS)

Chullen, Cinda; Conger, Bruce; Korona, Adam; Kanne, Bryan; McMillin, Summer; Paul, Thomas; Norcross, Jason; Alonso, Jesus Delgado; Swickrath, Mike

2015-01-01

NASA is pursuing technology development of an Advanced Extravehicular Mobility Unit (AEMU) which is an integrated assembly made up of primarily a pressure garment system and a portable life support subsystem (PLSS). The PLSS is further composed of an oxygen subsystem, a ventilation subsystem, and a thermal subsystem. One of the key functions of the ventilation system is to remove and control the carbon dioxide (CO2) delivered to the crewmember. Carbon dioxide washout is the mechanism by which CO2 levels are controlled within the space suit helmet to limit the concentration of CO2 inhaled by the crew member. CO2 washout performance is a critical parameter needed to ensure proper and robust designs that are insensitive to human variabilities in a space suit. A suited manikin test apparatus (SMTA) was developed to augment testing of the PLSS ventilation loop in order to provide a lower cost and more controlled alternative to human testing. The CO2 removal function is performed by the regenerative Rapid Cycle Amine (RCA) within the PLSS ventilation loop and its performance is evaluated within the integrated SMTA and Ventilation Loop test system. This paper will provide a detailed description of the schematics, test configurations, and hardware components of this integrated system. Results and analysis of testing performed with this integrated system will be presented within this paper.

The Lack of Effect of Food on the Pharmacokinetics of ZX008 (Fenfluramine Oral Solution): Results of a Single-dose, Two-period Crossover Study.

PubMed

Gammaitoni, Arnold; Smith, Steven; Boyd, Brooks

2018-06-22

Fenfluramine is being developed as a low-dose adjunctive treatment for seizures in patients with Dravet syndrome and other epileptic encephalopathies, including Lennox-Gastaut syndrome. Most patients with Dravet syndrome receive multiple antiepileptic drugs, making it challenging for caregivers to track correct administration times. The present Phase I study was conducted to determine the effect of food on the pharmacokinetic properties of fenfluramine. Healthy nonsmoking subjects aged 18 to 50years were enrolled in an open-label, crossover, Phase I pharmacokinetic and safety profile study and received 2 single 0.8-mg/kg doses of ZX008 (fenfluramine hydrochloride oral solution), 1 after a 10-hour overnight fast and the other 30 minutes after the start of consumption of a high-fat breakfast, in a randomly assigned order. A washout period of at least 9days separated the 2 treatment periods. Venous blood samples were taken before each dose and periodically for 72hours after each dose for determination of concentrations of fenfluramine and its active metabolite norfenfluramine. Plasma pharmacokinetic parameters were estimated for each subject by noncompartmental analysis. In the 13 subjects completing both treatment periods, food had no effect on the rate or extent of absorption and bioavailability of fenfluramine as assessed by fed vs fasted adjusted geometric mean observed plasma C max (59.1vs 56.7 ng/mL; NS) and AUC 0-∞ (1640vs 1600 ng · h/mL; NS). Additionally, there was no impact of food on systemic exposure of norfenfluramine. Seven subjects reported at least 1 treatment-emergent adverse event; all treatment-emergent adverse events were mild in severity. The bioequivalence and tolerability of single 0.8-mg/kg oral doses of ZX008 in the fed and fasted states support ZX008 administration without regard to meals. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Pharmacokinetic interaction of flecainide and paroxetine in relation to the CYP2D6*10 allele in healthy Korean subjects

PubMed Central

Lim, Kyoung Soo; Cho, Joo-Youn; Jang, In-Jin; Kim, Bo-Hyung; Kim, JaeWoo; Jeon, Ji-Young; Tae, Yu-Mi; Yi, SoJeong; Eum, SoYoung; Shin, Sang-Goo; Yu, Kyung-Sang

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT The only existing study of CYP2D6*10-associated alterations in flecainide pharmacokinetics was retrospective. Paroxetine has been known as a strong inhibitor of CYP2D6. WHAT THIS STUDY ADDS This study reports that the extent of drug interaction between flecainide and paroxetine is influenced by the CYP2D6*10 allele in healthy subjects, which is frequent in Asians. AIMS The objectives were to evaluate the effect of CYP2D6 genetic polymorphism on the pharmacokinetics of flecainide, and also on the extent of drug interaction with paroxetine as a CYP2D6 inhibitor after a single oral administration in healthy subjects. METHODS An open-label, two-period, single-sequence, cross-over study was performed in 21 healthy Korean male volunteers (seven for CYP2D6*1/*1 or *1/*2, group 1; seven for CYP2D6*1/*10, group 2; seven for CYP2D6*10/*10 or *10/*36, group 3). Subjects were administered 200 mg of flecainide on day 1. After a 7-day wash-out period, subjects were administered 20 mg of paroxetine from day 8 to 14, and 200 mg of flecainide on day 15. Blood sampling was performed up to 72 h after flecainide administration. RESULTS Terminal elimination half-life and mean residence time (MRT) were significantly different among three genotype groups after a single oral administration of flecainide (P = 0.021, 0.011, respectively). Area under the concentration–time curve, terminal elimination half-life and MRT increased significantly after paroxetine co-administration only in groups 1 and 2. CONCLUSIONS This study reports that the extent of drug interaction between flecainide and paroxetine is influenced by the CYP2D6*10 allele in healthy subjects, which is frequent in Asians. PMID:18754843

41 CFR 102-118.405 - Are my agency's prepayment audited transportation bills subject to periodic postpayment audit...

Code of Federal Regulations, 2010 CFR

2010-07-01

... prepayment audited transportation bills subject to periodic postpayment audit oversight from the GSA Audit... Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION TRANSPORTATION 118-TRANSPORTATION PAYMENT AND AUDIT Prepayment Audits of Transportation Services Waivers from Mandatory Prepayment Audit...

Patterns of pulmonary perfusion scans in normal subjects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallace, J.M.; Moser, K.M.; Hartman, M.T.

1981-01-01

A vital factor conditioning the usage of the pulmonary perfusion (Q) scan in the evaluation of patients suspected of pulmonary embolism is the prevalence of abnormal Q scans in subjects free of cardiopulmonary disease. Because this prevalence has not been well defined, we performed Q scans in 80 nonsmoking subjects 18 to 29 yr of age having no known active cardiopulmonary disease. Each subject underwent a history, physical examination, electrocardiogram, spirometry, and PA chest roentgenogram, followed by a 6-view Q scan. Two subjects in whom a Q defect was suspected underwent a /sup 133/Xe equilibrium-washout ventilation (V) scan. All Qmore » scans were interpreted blindly and independently by 2 experienced readers. Seventy-nine of the 80 Q scans were read as normal. No subject demonstrated a lobar or segmental defect. One of the 80 subjects, who had a mild pectus excavatum, had a left upper lobe subsegmental defect, which was not seen on the V scan. Based on the statistical analysis of these data, no more than 3.68% of normal nonsmoking persons in this age group may have a lobar or segmental Q scan defect and no more than 6.77% may have a subsegmental defect (with 95% confidence). Therefore, our study indicated that Q scan defects, particularly lobar or segmental, are rarely present among normal nonsmokers in this age group.« less

Combined technetium radioisotope penile plethysmography and xenon washout: A technique for evaluating corpora cavernosal inflow and outflow during early tumescence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwartz, A.N.; Graham, M.M.

1991-03-01

Combined technetium radioisotope penile plethysmography and xenon washout is a new technique that measures both corporal arterial inflow and venous sinusoidal outflow during early tumescence in patients with erectile dysfunction. Fourteen patients were studied using 99mTc-RBCs to measure inflow and 133Xe or 127Xe in saline to measure outflow. Tumescence was induced by injecting papaverine intracorporally. Peak corporal rates corrected for inflow (r = 0.88) and uncorrected for outflow (r = 0.91) and change in volume over 2 min centered around peak inflow (r = 0.96) all correlated with angiography. Outflow measurements did not correlate with intracorporal resistance. Thus, outflow ratesmore » alone could not be used to predict venous sinusoidal competence. Normal inflow rate is greater than 20 ml/min; probable normal 12-20; indeterminate inflow 7-12; and abnormal inflow less than 7 ml/min. Technetium-99m radioisotope penile plethysmography and xenon washout can be performed together and both provide a method for simultaneously evaluating the relationship between corporal inflow and outflow rates in patients with erectile dysfunction.« less

Effects of stearidonic acid on serum triacylglycerol concentrations in overweight and obese subjects: a randomized controlled trial.

PubMed

Pieters, D J M; Mensink, R P

2015-01-01

Eicosapentaenoic acid (EPA), which may reduce the risk for coronary heart disease (CHD), can be synthesized at low rates from α-linolenic acid (ALA). The rate-limiting step for this conversion is the Δ6-desaturation of ALA into stearidonic acid (SDA). Thus providing oils rich in SDA may increase endogenous synthesis of EPA, which may subsequently lower serum triacylglycerol concentrations, an effect frequently observed after EPA supplementation. We therefore studied the effects of Echium oil on serum triacylglycerol concentrations and the omega-3 index, which correlate negatively with the risk for CHD. A randomized, double-blind, placebo-controlled crossover trial was conducted, in which 36 healthy overweight and slightly obese subjects daily received 10 g of Echium oil (providing 1.2 g of SDA) or a high oleic acid sunflower oil (HOSO) as control for 6 weeks, with a washout period of at least 14 days. Four subjects dropped out. Differences between periods were tested for statistical significance (P<0.05) using a paired t-test. Serum triacylglycerol and other lipid concentrations were not significantly affected by consumption of Echium oil compared with HOSO. Echium oil significantly increased percentage of EPA in red blood cell (RBC) membranes with 0.14 ± 0.25% (mean ± s.d.) compared with HOSO (P=0.02). No significant effects on docosahexaenoic acid in RBC membranes or on the omega-3 index were found. In healthy overweight and slightly obese subjects, an increased intake of SDA from Echium oil does not lower serum triacylglycerol concentrations. Despite an increase in the percentage of EPA in RBC membranes, the omega-3 index was not changed.

Effect of Polydextrose on Subjective Feelings of Appetite during the Satiation and Satiety Periods: A Systematic Review and Meta-Analysis.

PubMed

Ibarra, Alvin; Astbury, Nerys M; Olli, Kaisa; Alhoniemi, Esa; Tiihonen, Kirsti

2016-01-14

Subjective feelings of appetite are measured using visual analogue scales (VAS) in controlled trials. However, the methods used to analyze VAS during the Satiation (pre- to post-meal) and Satiety (post-meal to subsequent meal) periods vary broadly, making it difficult to compare results amongst independent studies testing the same product. This review proposes a methodology to analyze VAS during both the Satiation and Satiety periods, allowing us to compare results in a meta-analysis. A methodology to express VAS results as incremental areas under the curve (iAUC) for both the Satiation and Satiety periods is proposed using polydextrose as a case study. Further, a systematic review and meta-analysis on subjective feelings of appetite was conducted following the PRISMA methodology. Meta-analyses were expressed as Standardized Mean Difference (SMD). Seven studies were included in the meta-analysis. There were important differences in the methods used to analyze appetite ratings amongst these studies. The separate subjective feelings of appetite reported were Hunger, Satisfaction, Fullness, Prospective Food Consumption, and the Desire to Eat. The method proposed here allowed the results of the different studies to be homogenized. The meta-analysis showed that Desire to Eat during the Satiation period favors polydextrose for the reduction of this subjective feeling of appetite (SMD = 0.24, I² < 0.01, p = 0.018); this effect was also significant in the sub-analysis by sex for the male population (SMD = 0.35, I² < 0.01, p = 0.015). There were no other significant results. It is possible to compare VAS results from separate studies. The assessment of iAUC for both the Satiation and Satiety periods generates results of homogeneous magnitudes. This case study demonstrates, for the first time, that polydextrose reduces the Desire to Eat during the Satiation period. This may explain, at least in part, the observed effects of polydextrose on the reduction of levels of energy

Effect of Polydextrose on Subjective Feelings of Appetite during the Satiation and Satiety Periods: A Systematic Review and Meta-Analysis

PubMed Central

Ibarra, Alvin; Astbury, Nerys M.; Olli, Kaisa; Alhoniemi, Esa; Tiihonen, Kirsti

2016-01-01

Introduction: Subjective feelings of appetite are measured using visual analogue scales (VAS) in controlled trials. However, the methods used to analyze VAS during the Satiation (pre- to post-meal) and Satiety (post-meal to subsequent meal) periods vary broadly, making it difficult to compare results amongst independent studies testing the same product. This review proposes a methodology to analyze VAS during both the Satiation and Satiety periods, allowing us to compare results in a meta-analysis. Methods: A methodology to express VAS results as incremental areas under the curve (iAUC) for both the Satiation and Satiety periods is proposed using polydextrose as a case study. Further, a systematic review and meta-analysis on subjective feelings of appetite was conducted following the PRISMA methodology. Meta-analyses were expressed as Standardized Mean Difference (SMD). Results: Seven studies were included in the meta-analysis. There were important differences in the methods used to analyze appetite ratings amongst these studies. The separate subjective feelings of appetite reported were Hunger, Satisfaction, Fullness, Prospective Food Consumption, and the Desire to Eat. The method proposed here allowed the results of the different studies to be homogenized. The meta-analysis showed that Desire to Eat during the Satiation period favors polydextrose for the reduction of this subjective feeling of appetite (SMD = 0.24, I2 < 0.01, p = 0.018); this effect was also significant in the sub-analysis by sex for the male population (SMD = 0.35, I2 < 0.01, p = 0.015). There were no other significant results. Conclusion: It is possible to compare VAS results from separate studies. The assessment of iAUC for both the Satiation and Satiety periods generates results of homogeneous magnitudes. This case study demonstrates, for the first time, that polydextrose reduces the Desire to Eat during the Satiation period. This may explain, at least in part, the observed effects of

Effects of fresh gas flow, tidal volume, and charcoal filters on the washout of sevoflurane from the Datex Ohmeda (GE) Aisys, Aestiva/5, and Excel 210 SE Anesthesia Workstations.

PubMed

Sabouri, A Sassan; Lerman, Jerrold; Heard, Christopher

2014-10-01

We investigated the effects of tidal volume (VT), fresh gas flow (FGF), and a charcoal filter in the inspiratory limb on the washout of sevoflurane from the following Datex Ohmeda (GE) Anesthesia Workstations (AWSs): Aisys, Aestiva/5, and Excel 210SE. After equilibrating the AWSs with 2% sevoflurane, the anesthetic was discontinued, and the absorbent anesthesia breathing circuit (ABC), reservoir bag, and test lung were changed. The lung was ventilated with 350 or 200 mL·breath(-1), 15 breaths·min(-1), and a FGF of 10 L·min(-1) while the washout of sevoflurane was performed in triplicate using a calibrated Datex Ohmeda Capnomac Ultima™ and a calibrated MIRAN SapphIRe XL ambient air analyzer until the concentration was ≤ 10 parts per million (ppm). The effects of decreasing the FGF to 5 and 2 L·min(-1) after the initial washout and of a charcoal filter in the ABC were recorded separately. The median washout times with the Aisys AWS (14 min, P < 0.01) and the Aestiva/5 (17 min, P < 0.001) with VT 350 mL·breath(-1) were significantly less than that with the Excel 210SE (32 min). The mean (95% confidence interval) washout time with the Aisys increased to 23.5 (21.5 to 25.5) min with VT 200 mL·breath(-1) (P < 0.01). Decreasing the FGF from 10 to 5 and 2 L·min(-1) with the Aisys caused a rebound in sevoflurane concentration to ≥ 50 ppm. Placement of a charcoal filter in the inspiratory limb reduced the sevoflurane concentration to < 2 ppm in the Aisys and Aestiva/5 AWSs within two minutes. The GE AWSs should be purged with large FGFs and VTs ~350 mL·breath(-1) for ~25 min to achieve 10 ppm sevoflurane. The FGF should be maintained to avoid a rebound in anesthetic concentration. Charcoal filters rapidly decrease the anesthetic concentration to < 2 ppm.

Effect of Food and Esomeprazole on the Pharmacokinetics of Alectinib, a Highly Selective ALK Inhibitor, in Healthy Subjects.

PubMed

Morcos, Peter N; Guerini, Elena; Parrott, Neil; Dall, Georgina; Blotner, Steven; Bogman, Katrijn; Sturm, Carolina; Balas, Bogdana; Martin-Facklam, Meret; Phipps, Alex

2017-07-01

Alectinib, an anaplastic lymphoma kinase (ALK) inhibitor, is approved for treatment of patients with ALK+ non-small cell lung cancer who have progressed, on or are intolerant to, crizotinib. This study assessed the effect of a high-fat meal and the proton pump inhibitor, esomeprazole, on the pharmacokinetics (PK) of alectinib. This was an open-label, 2-group study in healthy subjects. In group 1 (n = 18), subjects were randomly assigned to a 2-treatment (A, fasted conditions; B, following a high-fat meal), 2-sequence (AB or BA) crossover assessment, separated by a 10-day washout. In group 2 (n = 24), subjects were enrolled in a 2-period, fixed-sequence crossover assessment to evaluate the effect of esomeprazole. PK parameters were evaluated for alectinib, its major similarly active metabolite, M4, and the combined exposure of alectinib and M4. Administration of alectinib following a high-fat meal substantially increased the combined exposure of alectinib and M4 to 331% (90%CI, 279%-393%) and 311% (90%CI, 273%-355%) for C max and AUC 0-∞ , respectively, versus fasted conditions. Coadministration of esomeprazole had no clinically relevant effect on the combined exposure of alectinib and M4. Alectinib should be administered under fed conditions to maximize its bioavailability, whereas no restrictions are required with antisecretory agents. © 2016, The American College of Clinical Pharmacology.

Bioavailability of two oral-tablet and two oral-suspension formulations of naproxen sodium/paracetamol (acetaminophen): single-dose, randomized, open-label, two-period crossover comparisons in healthy Mexican adult subjects.

PubMed

Palma-Aguirre, Jose Antonio; Villalpando-Hernández, Jorge; Novoa-Heckel, Germán; Oliva, Iván; Cariño, Lizbeth; López-Bojórquez, Ericka; Burke-Fraga, Victoria; Namur, Salvador; González-de la Parra, Mario

2009-02-01

Naproxen sodium/paracetamol (acetaminophen) is a combination for the treatment of symptomatic pain and fever marketed both as a prescription and an over-the-counter product in Mexico. The aim of these 2 studies was to compare the bioavailability and to determine the bioequivalence of 2 test formulations (an oral-tablet formulation containing the combination of naproxen sodium/paracetamol 275/300 mg and an oral-suspension formulation containing the combination of naproxen sodium/paracetamol 375/300 mg per 15 mL) with their corresponding listed reference-drug formulations in Mexico (a list issued by Mexican health authorities). Two separate, single-dose, randomized, open-label, 2-period crossover, postmarketing studies were conducted. For each study, a different set of eligible subjects was selected comprising healthy Mexican adults of either sex, and subjects were randomly assigned to receive 1 test formulation of the combination of naproxen sodium/paracetamol followed by the corresponding reference-drug formulation, or vice versa, with a 1-week washout period between doses. After a 12-hour overnight fast, subjects received a single dose of naproxen sodium/paracetamol 275/300-mg tablet or naproxen sodium/paracetamol 375/300 mg per 15 mL suspension, depending on the study. For the analysis of pharmacokinetic parameters, including C(max), AUC from time 0 (baseline) to 48 hours (AUC(0-48)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline and at 0.16, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours after administration. The formulations were considered bioequivalent if the geometric mean ratios (test/reference) of the C(max) and AUC were within the predetermined range of 80% to 125%. Tolerability was determined by clinical assessment, monitoring vital signs, laboratory analysis results, and subject interviews regarding adverse events. A total of 26 subjects (15 men, 11 women; mean [SD] age, 29 [8] years

Minimizing atelectasis formation during general anaesthesia—oxygen washout is a non-essential supplement to PEEP

PubMed Central

Östberg, Erland; Auner, Udo; Enlund, Mats; Zetterström, Henrik; Edmark, Lennart

2017-01-01

Background Following preoxygenation and induction of anaesthesia, most patients develop atelectasis. We hypothesized that an immediate restoration to a low oxygen level in the alveoli would prevent atelectasis formation and improve oxygenation during the ensuing anaesthesia. Methods We randomly assigned 24 patients to either a control group (n = 12) or an intervention group (n = 12) receiving an oxygen washout procedure directly after intubation. Both groups were, depending on body mass index, ventilated with a positive end-expiratory pressure (PEEP) of 6–8 cmH2O during surgery. The atelectasis area was studied by computed tomography before emergence. Oxygenation levels were evaluated by measuring blood gases and calculating estimated venous admixture (EVA). Results The atelectasis areas expressed as percentages of the total lung area were 2.0 (1.5–2.7) (median [interquartile range]) and 1.8 (1.4–3.3) in the intervention and control groups, respectively. The difference was non-significant, and also oxygenation was similar between the two groups. Compared to oxygenation before the start of anaesthesia, oxygenation at the end of surgery was improved in the intervention group, mean (SD) EVA from 7.6% (6.6%) to 3.9% (2.9%) (P = .019) and preserved in the control group, mean (SD) EVA from 5.0% (5.3%) to 5.6% (7.1%) (P = .59). Conclusion Although the oxygen washout restored a low pulmonary oxygen level within minutes, it did not further reduce atelectasis size. Both study groups had small atelectasis and good oxygenation. These results suggest that a moderate PEEP alone is sufficient to minimize atelectasis and maintain oxygenation in healthy patients. PMID:28434271

Minimizing atelectasis formation during general anaesthesia-oxygen washout is a non-essential supplement to PEEP.

PubMed

Östberg, Erland; Auner, Udo; Enlund, Mats; Zetterström, Henrik; Edmark, Lennart

2017-06-01

Following preoxygenation and induction of anaesthesia, most patients develop atelectasis. We hypothesized that an immediate restoration to a low oxygen level in the alveoli would prevent atelectasis formation and improve oxygenation during the ensuing anaesthesia. We randomly assigned 24 patients to either a control group (n = 12) or an intervention group (n = 12) receiving an oxygen washout procedure directly after intubation. Both groups were, depending on body mass index, ventilated with a positive end-expiratory pressure (PEEP) of 6-8 cmH 2 O during surgery. The atelectasis area was studied by computed tomography before emergence. Oxygenation levels were evaluated by measuring blood gases and calculating estimated venous admixture (EVA). The atelectasis areas expressed as percentages of the total lung area were 2.0 (1.5-2.7) (median [interquartile range]) and 1.8 (1.4-3.3) in the intervention and control groups, respectively. The difference was non-significant, and also oxygenation was similar between the two groups. Compared to oxygenation before the start of anaesthesia, oxygenation at the end of surgery was improved in the intervention group, mean (SD) EVA from 7.6% (6.6%) to 3.9% (2.9%) (P = .019) and preserved in the control group, mean (SD) EVA from 5.0% (5.3%) to 5.6% (7.1%) (P = .59). Although the oxygen washout restored a low pulmonary oxygen level within minutes, it did not further reduce atelectasis size. Both study groups had small atelectasis and good oxygenation. These results suggest that a moderate PEEP alone is sufficient to minimize atelectasis and maintain oxygenation in healthy patients.

Effect of Oral Coadministration of Ascorbic Acid with Ling Zhi Preparation on Pharmacokinetics of Ganoderic Acid A in Healthy Male Subjects: A Randomized Crossover Study

PubMed Central

Tawasri, Patcharanee; Ampasavate, Chadarat; Tharatha, Somsak

2016-01-01

The objective of this randomized, open-label, single-dose, two-phase crossover study was to determine the effect of ascorbic acid on pharmacokinetics of ganoderic acid A, an important biologically active triterpenoid compound with anticancer activities, following oral administration of water extract of fruiting bodies of Ling Zhi in 12 healthy male subjects. Each subject was randomized to receive either one of the two regimens: (1) a single dose of 3,000 mg of the Ling Zhi preparation or (2) a single dose of 3,000 mg of the Ling Zhi preparation in combination with 2,500 mg of ascorbic acid. After a washout period of at least two weeks, subjects were switched to receive the alternate regimen. Blood samples were collected in each phase immediately before dosing and at specific time points for 8 hours after dosing. Plasma ganoderic acid A concentrations were quantified using liquid chromatography-mass spectrometry (LC-MS). The pharmacokinetic parameters analyzed were maximal plasma concentration (C max), time to reach peak concentration (T max), area under the plasma concentration-time curve (AUC), and half-life (t 1/2). An oral coadministration of ascorbic acid with Ling Zhi preparation did not significantly alter the pharmacokinetic parameters of ganoderic acid A in healthy male subjects. PMID:27747224

Effect of pistachio consumption on the modulation of urinary gut microbiota-related metabolites in prediabetic subjects.

PubMed

Hernández-Alonso, Pablo; Cañueto, Daniel; Giardina, Simona; Salas-Salvadó, Jordi; Cañellas, Nicolau; Correig, Xavier; Bulló, Mònica

2017-07-01

The specific nutritional composition of nuts could affect different metabolic pathways involved in a broad range of metabolic diseases. We therefore investigated whether chronic consumption of pistachio nuts modifies the urine metabolome in prediabetic subjects. We designed a randomized crossover clinical trial in 39 prediabetic subjects. They consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out. Nuclear magnetic resonance (NRM) was performed to determine changes in 24-h urine metabolites. Significant changes in urine metabolites according to the different intervention periods were found in uni- and multivariate analysis. Score plot of the first two components of the multilevel partial least squares discriminant analysis (ML-PLS-DA) showed a clear separation of the intervention periods. Three metabolites related with gut microbiota metabolism (i.e., hippurate, p-cresol sulfate and dimethylamine) were found decreased in PD compared with CD (P<.05). Moreover, cis-aconitate [intermediate of the tricarboxylic acid (TCA)] was also found decreased following PD compared with CD. Intragroup analysis showed that creatinine levels were significantly increased in PD (P=.023), whereas trimethylamine N-oxide (TMAO) was found significantly reduced following PD (P=.034). Our results suggest that chronic pistachio consumption may modulate some urinary metabolites related to gut microbiota metabolism and the TCA cycle; all associated with metabolic derangements associated with insulin resistance and Type 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

Maintaining Adequate CO2 Washout for an Advanced EMU via a New Rapid Cycle Amine Technology

NASA Technical Reports Server (NTRS)

Chullen, Cinda; Conger, Bruce

2012-01-01

Over the past several years, NASA has realized tremendous progress in Extravehicular Activity (EVA) technology development. This has been evidenced by the progressive development of a new Rapid Cycle Amine (RCA) system for the Advanced Extravehicular Mobility Unit (AEMU) Portable Life Support Subsystem (PLSS). The PLSS is responsible for the life support of the crew member in the spacesuit. The RCA technology is responsible for carbon dioxide (CO2) and humidity control. Another aspect of the RCA is that it is on-back vacuum-regenerable, efficient, and reliable. The RCA also simplifies the PLSS schematic by eliminating the need for a condensing heat exchanger for humidity control in the current EMU. As development progresses on the RCA, it is important that the sizing be optimized so that the demand on the PLSS battery is minimized. As well, maintaining the CO2 washout at adequate levels during an EVA is an absolute requirement of the RCA and associated ventilation system. Testing has been underway in-house at NASA Johnson Space Center and analysis has been initiated to evaluate whether the technology provides exemplary performance in ensuring that the CO2 is removed sufficiently and the ventilation flow is adequate for maintaining CO2 washout in the AEMU spacesuit helmet of the crew member during an EVA. This paper will review the recent developments of the RCA unit, testing planned in-house with a spacesuit simulator, and the associated analytical work along with insights from the medical aspect on the testing. 1

SSRI effects on pyschomotor performance: assessment of citalopram and escitalopram on normal subjects.

PubMed

Paul, Michel A; Gray, Gary W; Love, Ryan J; Lange, Marvin

2007-07-01

Standard aeromedical doctrine dictates that aircrew receiving treatment for depression are grounded during treatment and follow-up observation, generally amounting to at least 1 yr. The Canadian Forces has initiated a program to return selected aircrew being treated for depression to restricted flying duties once stabilized on an approved antidepressant with resolution of depression. The currently approved medications are sertraline (a selective serotonin reuptake inhibitor) and bupropion (noradrenaline and dopamine reuptake inhibitor). This study was undertaken to determine whether or not citalopram or escitalopram affect psychomotor performance. In a double-blind crossover protocol with counter-balanced treatment order, 24 normal volunteer subjects (14 men and 10 women) were assessed for psychomotor performance during placebo, citalopram (40 mg), and escitalopram (20 mg) treatment. Each treatment arm lasted 2 wk, involving a daily morning ingestion of one capsule. There was a 1-wk washout period between medication courses. Subjects completed a drug side-effect questionnaire and were tested on three psychomotor test batteries once per week. Neither citalopram nor escitalopram affected serial reaction time, logical reasoning, serial subtraction, multitask, or MacWorth clock task performance. While we found some of the expected side effects due to citalopram and escitalopram, there was no impact on psychomotor performance. These findings support the possibility of using citalopram and escitalopram for returning aircrew to restricted flight duties (non-tactical flying) under close observation as a maintenance treatment after full resolution of depression.

Absorption spectrum of a two-level system subjected to a periodic pulse sequence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fotso, H. F.; Dobrovitski, V. V.

We investigate how the quantum control of a two-level system (TLS) coupled to photons can modify and tune the TLS’s photon absorption spectrum. Tuning and controlling the emission and the absorption is of much interest e.g. for the development of efficient interfaces between stationary and flying qubits in modern architectures for quantum computation and quantum communication. We consider the periodic pulse control, where the TLS is subjected to a periodic sequence of the near-resonant Rabi driving pulses, each pulse implementing a 180° rotation. For small inter-pulse delays, the absorption spectrum features a pronounced peak of stimulated emission at the pulsemore » frequency, as well as equidistant satellite peaks with smaller spectral weights. As long as the detuning between the carrier frequency of the driving and the TLS transition frequency remains moderate, this spectral shape shows little change. Therefore, the quantum control allows shifting the absorption peak to a desired position, and locks the absorption peak to the carrier frequency of the driving pulses. Detailed description of the spectrum, and its evolution as a function time, the inter-pulse spacing and the detuning, is presented.« less

Absorption spectrum of a two-level system subjected to a periodic pulse sequence

DOE PAGES

Fotso, H. F.; Dobrovitski, V. V.

2017-06-01

We investigate how the quantum control of a two-level system (TLS) coupled to photons can modify and tune the TLS’s photon absorption spectrum. Tuning and controlling the emission and the absorption is of much interest e.g. for the development of efficient interfaces between stationary and flying qubits in modern architectures for quantum computation and quantum communication. We consider the periodic pulse control, where the TLS is subjected to a periodic sequence of the near-resonant Rabi driving pulses, each pulse implementing a 180° rotation. For small inter-pulse delays, the absorption spectrum features a pronounced peak of stimulated emission at the pulsemore » frequency, as well as equidistant satellite peaks with smaller spectral weights. As long as the detuning between the carrier frequency of the driving and the TLS transition frequency remains moderate, this spectral shape shows little change. Therefore, the quantum control allows shifting the absorption peak to a desired position, and locks the absorption peak to the carrier frequency of the driving pulses. Detailed description of the spectrum, and its evolution as a function time, the inter-pulse spacing and the detuning, is presented.« less

Special Report on the Data Collection Programs for the Ground Based Nitrogen Washout Experiment. Volume 2 - Detailed Program Descriptions, Listings, Examples and Hardware Specifications

NASA Technical Reports Server (NTRS)

1982-01-01

Personal data input, decompression data, nitrogen washout, nitrogen data, and update computer programs are described. Input data and formats; program output, reports, and data; program flowcharts; program listings; sample runs with input and output pages; hardware operation; and engineering data are provided.

Assessment of Drug-Drug Interaction Potential Between Atorvastatin and LCZ696, A Novel Angiotensin Receptor Neprilysin Inhibitor, in Healthy Chinese Male Subjects.

PubMed

Ayalasomayajula, Surya; Pan, Wei; Han, Yi; Yang, Fan; Langenickel, Thomas; Pal, Parasar; Zhou, Wei; Yuan, Yaozong; Rajman, Iris; Sunkara, Gangadhar

2017-04-01

LCZ696 (sacubitril/valsartan), a novel angiotensin receptor neprilysin inhibitor has been recently approved for the treatment of patients with heart failure (HF) and reduced ejection fraction. As several HF patients are likely to use statins as co-medications, the potential for a pharmacokinetic drug-drug interaction between atorvastatin and LCZ696 was evaluated. This was an open-label, three-period, single-sequence study in 28 healthy Chinese male subjects wherein LCZ696 200 mg was administered twice daily for 5 days in period 1. Following a washout period, atorvastatin 80 mg was administered once daily for 4 days (period 2) and subsequently co-administered with LCZ696 200 mg for 5 days (period 3). Serial plasma samples were collected to determine pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan) and atorvastatin and its metabolites. Atorvastatin co-administration had no effect on the pharmacokinetics of LBQ657, while the AUC τ,ss and C max,ss of sacubitril increased by 30 and 19 %, respectively, and the corresponding values for valsartan decreased by 19 and 9 %, respectively. Co-administration with LCZ696 increased C max,ss of atorvastatin, o-hydroxyatorvastatin, and p-hydroxyatorvastatin by 74, 68, and 108 %, respectively, and the AUC τ,ss of corresponding analytes increased by 34, 22, and 26 %, respectively. While atorvastatin had no significant impact on the pharmacokinetics of LCZ696 analytes upon co-administration, the C max of atorvastatin and its metabolites increased twofold, with a marginal increase in AUC (<1.3-fold). Multiple-dose administration of LCZ696 200 mg twice daily and atorvastatin 80 mg once daily either alone or in combination was generally safe and well tolerated in healthy subjects.

Isotropic, anisotropic, and borehole washout analyses in Gulf of Mexico Gas Hydrate Joint Industry Project Leg II, Alaminos Canyon well 21-A

USGS Publications Warehouse

Lee, Myung W.

2012-01-01

Through the use of three-dimensional seismic amplitude mapping, several gas hydrate prospects were identified in the Alaminos Canyon area of the Gulf of Mexico. Two of the prospects were drilled as part of the Gulf of Mexico Gas Hydrate Joint Industry Program Leg II in May 2009, and a suite of logging-while-drilling logs was acquired at each well site. Logging-while-drilling logs at the Alaminos Canyon 21–A site indicate that resistivities of approximately 2 ohm-meter and P-wave velocities of approximately 1.9 kilometers per second were measured in a possible gas-hydrate-bearing target sand interval between 540 and 632 feet below the sea floor. These values are slightly elevated relative to those measured in the hydrate-free sediment surrounding the sands. The initial well log analysis is inconclusive in determining the presence of gas hydrate in the logged sand interval, mainly because large washouts in the target interval degraded well log measurements. To assess gas-hydrate saturations, a method of compensating for the effect of washouts on the resistivity and acoustic velocities is required. To meet this need, a method is presented that models the washed-out portion of the borehole as a vertical layer filled with seawater (drilling fluid). Owing to the anisotropic nature of this geometry, the apparent anisotropic resistivities and velocities caused by the vertical layer are used to correct measured log values. By incorporating the conventional marine seismic data into the well log analysis of the washout-corrected well logs, the gas-hydrate saturation at well site AC21–A was estimated to be in the range of 13 percent. Because gas hydrates in the vertical fractures were observed, anisotropic rock physics models were also applied to estimate gas-hydrate saturations.

Safety of HTX-019 (intravenous aprepitant) and fosaprepitant in healthy subjects.

PubMed

Ottoboni, Tom; Lauw, Michael; Keller, Mary Rose; Cravets, Matt; Manhard, Kimberly; Clendeninn, Neil; Quart, Barry

2018-06-06

Evaluate safety of HTX-019, a novel polysorbate 80- and synthetic surfactant-free intravenous formulation of neurokinin 1 receptor antagonist aprepitant for chemotherapy-induced nausea and vomiting. Two open-label, randomized, two-way crossover studies evaluated treatment-emergent adverse events (TEAEs) in 200 healthy subjects. Subjects received HTX-019 130 mg (30-min infusion) and fosaprepitant 150 mg (20- or 30-min infusion), with ≥7-day washout between doses. Less than or equal to 30 min after start of infusion, TEAEs occurred in 5 (3%) HTX-019 and 30 (15%) fosaprepitant recipients. No HTX-019 recipients had infusion-site adverse events, versus 15 (8%) fosaprepitant recipients. Treatment-related dyspnea occurred in one HTX-019 and six fosaprepitant recipients. No severe/serious TEAEs occurred; all TEAEs resolved. HTX-019 may provide a safer aprepitant formulation than fosaprepitant for chemotherapy-induced nausea and vomiting prevention.

Maintaining Adequate CO2 Washout for an Advanced EMU via a New Rapid Cycle Amine Technology

NASA Technical Reports Server (NTRS)

Chullen, Cinda

2011-01-01

Over the past several years, NASA has realized tremendous progress in Extravehicular Activity (EVA) technology development. This has been evidenced by the progressive development of a new Rapic Cycle Amine (RCA) system for the Advanced Extravehicular Mobility Unit (AEMU) Portable Life Support Subsystem (PLSS). The PLSS is responsible for the life support of the crew member in the spacesuit. The RCA technology is responsible for carbon dioxide (CO2) and humidity control. Another aspect of the RCA is that it is on-back vacuum-regenerable, efficient, and reliable. The RCA also simplifies the PLSS schematic by eliminating the need for a condensing heat exchanger for humidity control in the current EMU. As development progresses on the RCA, it is important that the sizing be optimized so that the demand on the PLSS battery is minimized. As well, maintaining the CO2 washout at adequate levels during an EVA is an absolute requirement of the RCA and associated ventilation system. Testing has been underway in-house at NASA Johnson Space Center and analysis has been initiated to evaluate whether the technology provides exemplary performance in ensuring that the CO2 is removed sufficiently enough and the ventilation flow is adequate enough to maintain CO2 1 Project Engineer, Space Suit and Crew Survival Systems Branch, Crew and Thermal Systems Division, 2101 NASA Parkway, Houston, TX 77058/EC5. washout in the AEMU spacesuit helmet of the crew member during an EVA. This paper will review the recent developments of the RCA unit, the testing results performed in-house with a spacesuit simulator, and the associated analytical work along with insights from the medical aspect on the testing.

Three different up-titration regimens of ponesimod, an S1P1 receptor modulator, in healthy subjects.

PubMed

Scherz, Michael W; Brossard, Patrick; D'Ambrosio, Daniele; Ipek, Murat; Dingemanse, Jasper

2015-06-01

Ponesimod is a selective S1P1 receptor modulator, and induces dose-dependent reduction of circulating lymphocytes upon oral dosing. Previous studies showed that single doses up to 75 mg or multiple doses up to 40 mg once daily are well tolerated, and heart rate (HR) reduction and atrio-ventricular conduction delays upon treatment initiation are reduced by gradual up-titration to the maintenance dose. This single-center, open-label, randomized, multiple-dose, 3-treatment, 3-way crossover study compared the tolerability, safety, pharmacokinetics, cardiodynamics, and effects on lymphocytes of 3 different up-titration regimens of ponesimod in healthy male and female subjects. Up-titration regimens comprised escalating periods of b.i.d. dosing (2.5 or 5 mg) and q.d. dosing (10 or 20 mg or both). After the third up-titration period a variable-duration washout period of 1-3 days was followed by re-challenge with a single 20-mg dose of ponesimod. Adverse events were transient and mild to moderate in intensity, not different between regimens. HR decrease after the first dose was greater than after all subsequent doses, including up-titration doses. Little or no HR change was observed with morning doses of b.i.d. regimens, suggesting that 2.5 and 5 mg b.i.d. are sufficient to sustain cardiac desensitization for the 12-hours dosing interval. © 2015, The American College of Clinical Pharmacology.

Wheat bran extract alters colonic fermentation and microbial composition, but does not affect faecal water toxicity: a randomised controlled trial in healthy subjects.

PubMed

Windey, Karen; De Preter, Vicky; Huys, Geert; Broekaert, Willem F; Delcour, Jan A; Louat, Thierry; Herman, Jean; Verbeke, Kristin

2015-01-28

Wheat bran extract (WBE), containing arabinoxylan-oligosaccharides that are potential prebiotic substrates, has been shown to modify bacterial colonic fermentation in human subjects and to beneficially affect the development of colorectal cancer (CRC) in rats. However, it is unclear whether these changes in fermentation are able to reduce the risk of developing CRC in humans. The aim of the present study was to evaluate the effects of WBE on the markers of CRC risk in healthy volunteers, and to correlate these effects with colonic fermentation. A total of twenty healthy subjects were enrolled in a double-blind, cross-over, randomised, controlled trial in which the subjects ingested WBE (10 g/d) or placebo (maltodextrin, 10 g/d) for 3 weeks, separated by a 3-week washout period. At the end of each study period, colonic handling of NH3 was evaluated using the biomarker lactose[15N, 15N']ureide, colonic fermentation was characterised through a metabolomics approach, and the predominant microbial composition was analysed using denaturing gradient gel electrophoresis. As markers of CRC risk, faecal water genotoxicity was determined using the comet assay and faecal water cytotoxicity using a colorimetric cell viability assay. Intake of WBE induced a shift from urinary to faecal 15N excretion, indicating a stimulation of colonic bacterial activity and/or growth. Microbial analysis revealed a selective stimulation of Bifidobacterium adolescentis. In addition, WBE altered the colonic fermentation pattern and significantly reduced colonic protein fermentation compared with the run-in period. However, faecal water cytotoxicity and genotoxicity were not affected. Although intake of WBE clearly affected colonic fermentation and changed the composition of the microbiota, these changes were not associated with the changes in the markers of CRC risk.

Effects of oral hygiene products containing lactoperoxidase, lysozyme, and lactoferrin on the composition of whole saliva and on subjective oral symptoms in patients with xerostomia.

PubMed

Kirstilä, V; Lenander-Lumikari, M; Söderling, E; Tenovuo, J

1996-12-01

This study evaluates the effects of two oral hygiene products containing nonimmunoglobulin antimicrobial agents on whole saliva and on subjective oral symptoms in patients with xerostomia. Twenty patients used a lactoperoxidase-system-containing toothpaste (Biotene) combined with the use of a mouthrinse (Biotene), comprising also lysozyme and lactoferrin, for 4 weeks. Saliva samples were collected at base line, after 4 weeks' use of the products, and at the end of a 4-week washout period. Samples were analyzed for selected biochemical and microbiologic factors. The effects on subjective oral symptoms were also recorded. A 4-week daily use of toothpaste and mouthrinse relieved the symptoms of oral dryness in 16 patients. The levels of salivary hypothiocyanite, lysozyme, lactoferrin, or myeloperoxidase activity did not change, but there was a significant decrease in salivary pH (P < 0.05), total peroxidase activity (P < 0.05), and total protein content (P = 0.01). In patients with the lowest salivary flow rates (n = 5) a significant (P > or = 0.04) increase was detected in salivary hypothiocyanite concentrations. No major changes occurred in salivary microflora. The products relieved subjective oral symptoms in most xerostomic patients, but this was not necessarily related to the presence of antimicrobial agents.

Modelling responses of the inert-gas washout and MRI to bronchoconstriction.

PubMed

Foy, Brody H; Kay, David; Bordas, Rafel

2017-01-01

Many lung diseases lead to an increase in ventilation heterogeneity (VH). Two clinical practices for the measurement of patient VH are in vivo imaging, and the inert gas multiple breath washout (MBW). In this study computational modelling was used to compare the responses of MBW indices LCI and s cond and MRI measured global and local ventilation indices, σ r and σ local , to constriction of airways in the conducting zone of the lungs. The simulations show that s cond , LCI and σ r behave quite similarly to each other, all being sensitive to increases in the severity of constriction, while exhibiting little sensitivity to the depth at which constriction occurs. In contrast, the local MRI index σ local shows strong sensitivity to depth of constriction, but lowered sensitivity to constriction severity. We finish with an analysis of the sensitivity of MRI indices to grid sizes, showing that results should be interpreted with reference to the image resolution. Overall we conclude that the application of both local and global VH measures may help to classify different types of bronchoconstriction. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of time-of-day and chest physiotherapy on multiple breath washout measures in children with clinically stable cystic fibrosis.

PubMed

Voldby, Christian; Green, Kent; Rosthøj, Susanne; Kongstad, Thomas; Philipsen, Lue; Buchvald, Frederik; Skov, Marianne; Pressler, Tania; Gustafsson, Per; Nielsen, Kim G

2018-01-01

In this pilot study we investigated daytime variation of multiple breath nitrogen washout (N2MBW) measures in children with clinically stable cystic fibrosis. To our knowledge the effect of time-of-day on multiple breath washout measures in patients with cystic fibrosis has not previously been reported. Furthermore, we assessed the influence of chest physiotherapy on N2MBW measures. Ten school children with cystic fibrosis performed N2MBW followed by spirometry and plethysmography in the morning and afternoon at three visits that were one month apart. Chest physiotherapy was performed immediately before the afternoon measurements at visit 2 and immediately before morning and afternoon measurements at visit 3. The influence of time-of-day and chest physiotherapy on the measures was evaluated using linear mixed models. There were adequate quality data from 8 children with median age (range) 9.6 (6.0; 15.1) years. Baseline lung clearance index (LCI) (range) was 9.0 (7.1; 13.0) and baseline FEV1% predicted was 97.5 (78.5; 117.9). No N2MBW measures were significantly influenced by time-of-day or chest physiotherapy. LCI (95% confidence interval) decreased non-significantly 0.05 (-0.32; 0.22) during the day and increased non-significantly 0.08 (-0.26; 0.42) after chest physiotherapy. All spirometric measures were unaffected by time-of-day and chest physiotherapy. For plethysmographic measures FRCpleth decreased significantly (p<0.01) 110 mL during the day, whereas a borderline significant (p = 0.046) decrease in ΔFRCpleth-MBW during the day and a borderline significant (p = 0.03) increase in TLC after CPT were observed. This study demonstrated that the time-of-day as well as chest physiotherapy performed immediately prior to N2MBW had no consistent or significant influence on N2MBW measures. However, we emphasize that further studies of the effect of both daytime variation and the effect of chest physiotherapy on multiple breath washout measures are warranted.

Effect of a high bicarbonate mineral water on fasting and postprandial lipemia in moderately hypercholesterolemic subjects: a pilot study.

PubMed

Zair, Yassine; Kasbi-Chadli, Fatima; Housez, Beatrice; Pichelin, Mathieu; Cazaubiel, Murielle; Raoux, François; Ouguerram, Khadija

2013-07-18

During postprandial state, TG concentration is increasing and HDL cholesterol decreasing, leading to a transitory pro-atherosclerotic profile. Previous studies have reported that bicarbonate water improve postprandial lipemia. The objective of this study was to analyze the effect of a strongly bicarbonated mineral water on lipoprotein levels during fasting and postprandial state. A controlled, randomised, double-blind cross-over design was conducted in 12 moderately hypercholesterolemic subjects after a daily ingestion of 1.25 L of mineral (SY) or low mineral water during eight weeks separated by a one week wash-out period. Blood samples were collected in first visit to the hospital (V1) before water consumption (referent or SY) and in a second visit (V2) after eight week water consumption period. The effect of the consumed water was studied in fasting and in postprandial state during ingestion of a meal and 0.5 L of water. Comparison of data between V1 and V2 after SY consumption showed a significant decrease in triglyceridemia (23%), VLDL TG (31%) and tendency to a decrease of VLDL cholesterol (p = 0.066) at fasting state. Whatever the consumed water during postprandial state, the measurement of total areas under curves did not show a significant difference. No difference was observed between SY and referent water consumption for measured parameters at fasting and postprandial state. When subjects consumed SY we showed a decrease of their basal TG and VLDLTG. The unexpected absence of effect of high mineralized water on postprandial lipemia, probably related to experimental conditions, is discussed in the discussion section.

A comparative pharmacokinetic and tolerability analysis of the novel orotic acid salt form of tenofovir disoproxil and the fumaric acid salt form in healthy subjects

PubMed Central

Kim, Yu Kyong; Choi, Mun Ju; Oh, Tae Young; Yu, Kyung-Sang; Lee, SeungHwan

2017-01-01

A novel orotic acid salt form of tenofovir disoproxil (DA-2802) was developed and is expected to replace the fumaric acid salt form. The pharmacokinetic (PK) characteristics and tolerability profiles of DA-2802 were compared to those of tenofovir disoproxil fumarate (TDF, Viread®) in healthy subjects. A randomized, open-label, single-dose study was conducted in 36 healthy subjects using a two-treatment, two-period, and two-sequence crossover design. Subjects received a single oral dose of 319 mg DA-2802 or 300 mg TDF, during each period, with a 7-day washout. Serial blood samples were collected pre-dosing and up to 72 hours post-dosing in each period, for determination of serum tenofovir concentration, which was measured by ultra-performance liquid chromatography-tandem mass spectrometry. A non-compartmental method was used to obtain PK parameters of tenofovir. For comparison between the two tenofovir disoproxil salts, the 90% confidence intervals (90% CIs) of geometric mean ratios of DA-2802 to TDF for the maximum concentration (Cmax) and the area under the concentration–time curve to the last quantifiable concentration (AUC0–t) were determined. The tolerability profiles of tenofovir were assessed by evaluation of adverse events and vital signs, physical examination, ECG, and clinical laboratory tests. The serum tenofovir concentration–time profiles of DA-2802 or TDF were comparable in 32 subjects who completed the study. In both profiles, a two-compartmental elimination with first-order elimination kinetics in the terminal phase was reported in a few subjects, showing a secondary peak in the initial phase of elimination. The geometric mean ratio (90% CI) of DA-2802 to TDF was 0.898 (0.815–0.990) for Cmax and 0.904 (0.836–0.978) for AUC0–t. There were no clinically significant findings in the tolerability assessments. DA-2802 showed comparable PK characteristics and tolerability profiles to TDF. PMID:29158663

Effects of self washout structure on the antithrombogenicity and the hemolytic properties of a centrifugal pump.

PubMed

Wakisaka, Y; Taenaka, Y; Araki, K; Chikanari, K; Nakatani, T; Baba, Y; Anai, H; Eya, K; Toda, K; Takano, H

1997-02-01

Antithrombogenicity in an initial type (N1) of a centrifugal pump (CP) developed in our institute is provided by the central balancing hole of an impeller. A new CP (N2) was modified to obtain better antithrombogenicity, in which the balancing hole was widened to improve self washout flow velocity (Vsf), and an edge of the thrust bearing was rounded off to minimize flow separation. Effects of the modifications were assessed in vitro and in vivo studies. The Vsf of the N1 and the N2 evaluated by a Doppler velocimeter were 12.8 and 22.1 cm/s, respectively. Flow around the thrust bearing, which was visualized by a light cutting method, confirmed less flow stagnation in the N2. The hemolytic indices of the N1 and the N2 were 0.023 and 0.008 mg/dl, respectively. In vivo antithrombogenicity and the hemolytic properties of the N2 and the N1 were investigated without anticoagulation therapy in 3 goats. In each goat the N2 was driven for 1 week and exchanged for the N1, which was driven for the same period. Red thrombi at the thrust bearing were found in 2 N1s, and 2 small thrombi were on the impeller of another N1, whereas a thrombus of less than 1 mm3 at the TB was noted in 1 N2. Plasma free hemoglobin was not increased in either CP. These results indicate that the N2 has better antithrombogenicity and hemolytic properties than the N1.

[Minimal effective dose on serum cholesterol concentration and the safety evaluation of dressing containing plant sterol in Japanese subjects].

PubMed

Kurokawa, Masanori; Masuda, Yasunobu; Noda, Mitsuhiro; Marushima, Ranko; Usuda, Mika; Takeda, Sayaka; Hasegawa, Mineo; Homma, Yasuhiko; Sugano, Michihiro

2008-01-01

We examined the minimal effective dose on serum cholesterol concentration and the safety of dressing containing plant sterol in humans. EXP.1: Sixty-eight healthy Japanese males (total cholesterol (TC) > or = 170 mg/dL) were randomly divided into four groups, and were given 0, 400, 800 or 1200 mg/day of plant sterol in 15 g dressing for 4 weeks followed by the washout period of 4 weeks. Although there were no significant differences in serum TC and low-density lipoprotein cholesterol (LDL-C) concentrations among all groups after feeding plant sterol for 4 weeks, in 36 subjects with TC > or = 220 mg/dL, serum LDL-C concentration tended to reduce when received 800 or 1200 mg of plant sterol, and the difference between 0 and 1200 mg groups was statistically significant. The difference between 0 and 800 mg groups was near significant (p=0.053). Intake of 400 mg of plant sterol did not change serum LDL-C concentration. EXP.2: Twenty-one healthy Japanese subjects (TC > or = 180 mg/dL, 10 men, 11 women) were given 2400 mg/day of plant sterol in 45 g dressing for 4 weeks. Clinical data were all remained normal. These results indicated that minimal effective dose of the plant sterol on serum cholesterol concentration in healthy male subjects is around 800 mg/day, and intake of 2400 mg/day of plant sterol is regarded to be safe.

Ability of the new AT1 receptor blocker azilsartan to block angiotensin II-induced AT1 receptor activation after wash-out.

PubMed

Miura, Shin-ichiro; Matsuo, Yoshino; Nakayama, Asuka; Tomita, Sayo; Suematsu, Yasunori; Saku, Keijiro

2014-03-01

The recently approved angiotensin II (Ang II) type 1 (AT1) receptor blocker (ARB) azilsartan strongly reduces blood pressure (BP) in patients with hypertension. We previously reported that azilsartan showed unique binding behavior to the AT1 receptor because of its 5-oxo-1,2,4-oxadiazole moiety. However, the ability of azilsartan to block Ang II-dependent AT1 receptor activation is not yet clear. Azilsartan and a derivative of azilsartan (azilsartan-7H) that lacks a carboxyl group at the benzimidazole ring were used. Ang II-induced inositol phosphate (IP) production and extracellular signal-regulated kinase (ERK) activation were analyzed in a cell-based wash-out assay. Azilsartan, but not azilsartan-7H, completely blocked Ang II-induced IP production and ERK activation. Our previous report demonstrated that azilsartan mainly interacts with Tyr(113), Lys(199), and Gln(257) in the AT1 receptor. The interactions between azilsartan and Tyr(113) and Gln(257), but not Lys(199), were critical for blocking Ang II-induced IP production and ERK activation after wash-out. Although our findings regarding the molecule-specific effects of azilsartan are based on basic research, they may lead to an exciting insight into the mechanism of azilsartan.

Do changes in subjective sleep and biological rhythms predict worsening in postpartum depressive symptoms? A prospective study across the perinatal period.

PubMed

Krawczak, Elizabeth M; Minuzzi, Luciano; Hidalgo, Maria Paz; Frey, Benicio N

2016-08-01

Abnormalities of sleep and biological rhythms have been widely implicated in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). However, less is known about the influence of biological rhythm disruptions across the perinatal period on postpartum depression (PPD). The objective of this study was to prospectively evaluate the relationship between subjective changes in both sleep and biological rhythms and worsening of depressive symptoms from pregnancy to the postpartum period in women with and without mood disorders. Eighty-three participants (38 euthymic women with a history of a mood disorder and 45 healthy controls) were studied. Participants completed subjective assessments of sleep (Pittsburgh Sleep Quality Index), biological rhythm disturbances (Biological Rhythms Interview of Assessment in Neuropsychiatry), and depressive symptoms (Edinburgh Postnatal Depression Scale) prospectively at two time points: third trimester of pregnancy and at 6-12 weeks postpartum. Multivariate regression analyses showed that changes in biological rhythms across the perinatal period predicted worsening of depressive symptoms in both groups. Moreover, women with a history of a mood disorder showed higher levels of sleep and biological rhythm disruption during both pregnancy and the postpartum period. These findings suggest that disruptions in biological rhythms during the perinatal period increase the risk for postpartum mood worsening in healthy pregnant as well as in pregnant women with a history of mood disorders.

The risk of river pollution due to washout from contaminated floodplain water bodies during high floods

NASA Astrophysics Data System (ADS)

Lyubimova, Tatyana; Lepikhin, Anatoly; Parshakova, Yanina; Tiunov, Alexey

2016-04-01

Today, the potential impact of extremely high floods, which in the last years have become a rather frequent weather-related disaster, is the problem of primary concern. In studies of the potential impact of floods the emphasis is placed first of all on the estimation of possible flood zones and the analysis of the flow regimes in these zones. However, in some cases the hydrochemical parameters related to changes in the chemical composition of water are more important than the hydraulic parameters. It is generally believed that the higher is the flow rate, the more intensive is the process of dissolution, i.e. the lower is the concentration of limiting contaminants in water. However, this statement is valid provided that flooding does not activate new sources of water pollution such as contaminated floodplain water bodies located in the vicinity of water supply systems. Being quite reliable and safe at small and moderate discharges, in the case of extremely high level of river waters they become intensive sources of water pollution, essentially limiting the water consumption schedule for downstream water consumers. It should be noted that compared to the well-studied mechanisms of waste discharge due to failure of hydraulic engineering structures by flood waves, the mechanisms of pollutant washout from the contaminated floodplain water bodies by the flood waves is still poorly understood. We analyze the impacts of such weather-related events on the quality of water in the water intake system, taking as an example, the section of the Vyatka River located in the Prikamskaya lowland of the Russian Federation. The risk of river pollution due to washout from the contaminated floodplain water bodies during high floods is studied by hydrodynamical modeling in the framework of combined approach using one-, two- and three-dimensional hydrodynamic models are implemented and by in situ measurements. It is shown that during high floods the removal of pollutants from the

Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects

PubMed Central

Vinson, Joe A; Burnham, Bryan R; Nagendran, Mysore V

2012-01-01

Background Adult weight gain and obesity have become worldwide problems. Issues of cost and potential side effects of prescription weight loss drugs have led overweight and obese adults to try nutraceuticals that may aid weight loss. One promising nutraceutical is green coffee extract, which contains high concentrations of chlorogenic acids that are known to have health benefits and to influence glucose and fat metabolism. A 22-week crossover study was conducted to examine the efficacy and safety of a commercial green coffee extract product GCA™ at reducing weight and body mass in 16 overweight adults. Methods Subjects received high-dose GCA (1050 mg), low-dose GCA (700 mg), or placebo in separate six-week treatment periods followed by two-week washout periods to reduce any influence of preceding treatment. Treatments were counterbalanced between subjects. Primary measurements were body weight, body mass index, and percent body fat. Heart rate and blood pressure were also measured. Results Significant reductions were observed in body weight (−8.04 ± 2.31 kg), body mass index (−2.92 ± 0.85 kg/m2), and percent body fat (−4.44% ± 2.00%), as well as a small decrease in heart rate (−2.56 ± 2.85 beats per minute), but with no significant changes to diet over the course of the study. Importantly, the decreases occurred when subjects were taking GCA. Body mass index for six subjects shifted from preobesity to the normal weight range (<25.00 kg/m2). Conclusion The results are consistent with human and animal studies and a meta-analysis of the efficacy of green coffee extract in weight loss. The results suggest that GCA may be an effective nutraceutical in reducing weight in preobese adults, and may be an inexpensive means of preventing obesity in overweight adults. PMID:22291473

A 4-week study assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of the glucagon receptor antagonist PF-06291874 administered as monotherapy in subjects with type 2 diabetes mellitus.

PubMed

Bergman, Arthur; Tan, Beesan; Somayaji, Veena R; Calle, Roberto A; Kazierad, David J

2017-04-01

The glucagon receptor antagonist PF-06291874 has demonstrated robust glucose reductions in subjects with type 2 diabetes mellitus (T2DM) on background metformin. This study assessed the pharmacokinetics, pharmacodynamics, safety, and tolerability of PF-06291874 administered as monotherapy in subjects with T2DM. After a ≥4-week antidiabetic therapy washout period, 172 subjects were randomized to placebo or PF-06291874 15, 35, 75, or 150mg once daily for 28days. Mean daily glucose (MDG), fasting plasma glucose (FPG), and predefined safety endpoints were assessed at baseline and day 28. Dose-dependent reductions (placebo-adjusted) from baseline in MDG ranged from 40.3 to 68.8mg/dL and in FPG from 27.1 to 57.2mg/dL after 28days of dosing with PF-06291874. There were no significant changes in low-density lipoprotein cholesterol at doses ≤75mg relative to placebo. Small, dose-dependent increases in alanine aminotransferase and aspartate aminotransferase were observed; however, the incidence of these values >3×upper limit of normal was similar across doses. PF-06291874 exposures were consistent with previous studies and PF-06291874 was well tolerated, with minimal incidence of hypoglycemia. PF-06291874 as monotherapy was well tolerated and produced robust reductions in plasma glucose following 4weeks of dosing in subjects with T2DM. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of a Traditional Dietary Supplement with Coconut Milk and Soya Milk on the Lipid Profile in Normal Free Living Subjects

PubMed Central

Ekanayaka, R. A. I.; Ekanayaka, N. K.; Perera, B.; De Silva, P. G. S. M.

2013-01-01

Background. The effects of coconut fat and soya fat on serum lipids are controversial. This study was designed to investigate the lipid effects of coconut milk and soya milk supplementation on the lipid profile of free living healthy subjects. Methods. Sixty (60) healthy volunteers aged 18–57 years were given coconut milk porridge (CMP) for 5 days of the week for 8 weeks, followed by a 2-week washout period, subsequent to which they received isoenergetic soya milk porridge (SMP) for 8 weeks. Results. The LDL (low density lipoprotein) levels decreased with CMP and reached statistical significance in the total study population and in the >130 baseline LDL group. The HDL (high density lipoprotein) levels rose significantly with CMP supplementation (P = 0.000). Conclusions. We conclude that coconut fat in the form of CM does not cause a detrimental effect on the lipid profile in the general population and in fact is beneficial due to the decrease in LDL and rise in HDL. SMP will be of benefit only in those whose baseline LDL levels are elevated. PMID:24282632

Effect of mushroom diet on pharmacokinetics of gabapentin in healthy Chinese subjects

PubMed Central

Toh, Dorothy Su Lin; Limenta, Lie Michael George; Yee, Jie Yin; Wang, Ling-Zhi; Goh, Boon-Cher; Murray, Michael; Lee, Edmund Jon Deoon

2014-01-01

Aims This study evaluated the pharmacokinetics of gabapentin in Chinese subjects who received a diet rich in shiitake mushrooms. Shiitake mushrooms have been shown to contain high amount of ergothioneine. In vitro studies have shown that OCTN1-mediated secretion of gabapentin is trans-stimulated by ergothioneine. This study also investigated the concentrations of ergothioneine in plasma at baseline and following mushroom consumption. Methods Ten healthy male subjects were recruited and received a diet containing no mushrooms (treatment A) or a high mushroom diet (treatment B; after at least a 7 day washout period) 1 day prior to administration of a single oral dose of gabapentin 600 mg. Results Ingestion of shiitake mushrooms produced significant increases in plasma ergothioneine concentrations that were sustained for more than 48 h. A statistically significant but modest increase in the renal clearance (CLR) of gabapentin occurred after intake of the mushroom diet (91.1 ± 25.1 vs. 76.9 ± 20.6 ml min−1, P = 0.031). No significant changes in AUC(0,tlast) of gabapentin were observed (P = 0.726). Creatinine clearance did not correlate with CLR of gabapentin at baseline (treatment A). After ingestion of the mushroom diet, creatinine clearance accounted for 65.3% of the variance in CLR of gabapentin. Conclusions These data suggest that diet–drug pharmacokinetic interactions may occur during co-exposure to gabapentin and mushroom constituents. However, as it does not affect the AUC(0,tlast) of gabapentin, it may not have clinically important consequences. Shiitake mushrooms can also be used as a source of ergothioneine for future clinical studies. PMID:24168107

Effect of mushroom diet on pharmacokinetics of gabapentin in healthy Chinese subjects.

PubMed

Toh, Dorothy Su Lin; Limenta, Lie Michael George; Yee, Jie Yin; Wang, Ling-Zhi; Goh, Boon-Cher; Murray, Michael; Lee, Edmund Jon Deoon

2014-07-01

This study evaluated the pharmacokinetics of gabapentin in Chinese subjects who received a diet rich in shiitake mushrooms. Shiitake mushrooms have been shown to contain high amount of ergothioneine. In vitro studies have shown that OCTN1-mediated secretion of gabapentin is trans-stimulated by ergothioneine. This study also investigated the concentrations of ergothioneine in plasma at baseline and following mushroom consumption. Ten healthy male subjects were recruited and received a diet containing no mushrooms (treatment A) or a high mushroom diet (treatment B; after at least a 7 day washout period) 1 day prior to administration of a single oral dose of gabapentin 600 mg. Ingestion of shiitake mushrooms produced significant increases in plasma ergothioneine concentrations that were sustained for more than 48 h. A statistically significant but modest increase in the renal clearance (CLR ) of gabapentin occurred after intake of the mushroom diet (91.1 ± 25.1 vs. 76.9 ± 20.6 ml min(-1) , P = 0.031). No significant changes in AUC(0,tlast ) of gabapentin were observed (P = 0.726). Creatinine clearance did not correlate with CLR of gabapentin at baseline (treatment A). After ingestion of the mushroom diet, creatinine clearance accounted for 65.3% of the variance in CLR of gabapentin. These data suggest that diet-drug pharmacokinetic interactions may occur during co-exposure to gabapentin and mushroom constituents. However, as it does not affect the AUC(0,tlast ) of gabapentin, it may not have clinically important consequences. Shiitake mushrooms can also be used as a source of ergothioneine for future clinical studies. © 2013 The British Pharmacological Society.

Technical note: adipose tissue blood flow in miniature swine (Sus scrofa) using the 133xenon washout technique.

PubMed

Moher, H E; Carey, G B

2002-05-01

The purpose of this study was to examine the 133xenon washout technique as a viable method for measuring adipose tissue blood flow (ATBF) in swine. Using a total of 32 female Yucatan miniature swine (Sus scrofa), the partition coefficient for 133xenon in swine subcutaneous adipose tissue was determined and ATBF was measured at rest and under various physiological conditions. These conditions included feeding, anesthesia, epinephrine infusion, and acute exercise. The effects of epinephrine and acute exercise were examined in both sedentary and exercise-trained swine. The partition coefficient value for 133xenon in swine subcutaneous adipose tissue was 9.23+/-0.26 mL/g (mean +/- SD, n = 10). The average value for resting ATBF in swine was 3.98+/-2.72 mL/(100 g tissue-min) (n = 19). Feeding increased ATBF by approximately fivefold over fasting values, and isoflurane anesthesia significantly decreased ATBF compared to rest (1.64+/-1.12 vs 3.92+/-4.22 mL/[100 g x min], n = 10). A 30-min epinephrine infusion (1 microg/[kg BW x min]) significantly increased ATBF from a resting value of 3.13+/-2.61 to 10.35+/-5.31 mL/(100 g x min) (n = 12). Epinephrine infusion into exercise-trained swine increased ATBF to the same extent as when infused into sedentary swine. An acute, 20-min bout of exercise significantly increased ATBF in swine, and the sedentary swine showed a larger increase in ATBF than their exercise-trained littermates relative to rest: 7.83 vs 2.98 mL/(100 g x min). In conclusion, the 133xenon washout technique appears to be a viable method for measuring ATBF in swine; our findings are comparable to swine ATBF values reported using the microsphere method and are consistent with values reported in animal and human studies.

Pharmacokinetics of Mirabegron, a β3-Adrenoceptor Agonist for Treatment of Overactive Bladder, in Healthy East Asian Subjects.

PubMed

Iitsuka, Hiromi; van Gelderen, Marcel; Katashima, Masataka; Takusagawa, Shin; Sawamoto, Taiji

2015-05-01

The objective of these studies was to evaluate the pharmacokinetic profile, safety, and tolerability of mirabegron, a β3-adrenoceptor agonist for the treatment of overactive bladder, including food effects (low- or high-fat meals) and sex, in healthy East Asian subjects. In total, 5 pharmacokinetic studies of mirabegron were conducted in healthy East Asian subjects. Food effects were assessed in 3 randomized, single-dose studies in young Japanese male subjects (study 1), male and female subjects (study 2), and young Taiwanese male and female subjects (study 3). In the other 2 single- and multiple-dose studies in young Chinese male and female subjects (study 4 and study 5), mirabegron was administered as a single dose under fasted conditions. After the washout period, mirabegron was administered once daily under fed conditions for 8 days. Pharmacokinetic parameters were determined using noncompartmental methods. Safety and tolerability assessments included physical examinations, vital signs, 12-lead ECG, clinical laboratory tests (biochemistry, hematology, and urinalysis), and adverse event monitoring. After administration of single oral doses of mirabegron, exposure under fed conditions was lower than under fasted conditions in Japanese and Taiwanese subjects. In Japanese subjects, a greater reduction in mirabegron Cmax and AUC0-∞ was observed after a low-fat meal compared with a high-fat meal. In Chinese subjects, Cmax was reached at approximately 4.0 hours after single oral doses. Mirabegron accumulated 2- to 3-fold on once-daily dosing of multiple-dose relative to single-dose data. Steady state was reached within 7 days. After administration of mirabegron, mean values for Cmax and AUC in female subjects were higher than those in male subjects. Mirabegron was well tolerated in Japanese, Taiwanese, and Chinese subjects. Our studies confirm the higher exposure levels of mirabegron in female compared with male East Asian subjects as found earlier in Western

Benefits of sodium hexametaphosphate-containing chewing gum for extrinsic stain inhibition.

PubMed

Walters, Patricia A; Biesbrock, Aaron R; Bartizek, Robert D

2004-01-01

This study was designed to examine the ability of sodium hexametaphosphate delivered from a chewing gum to prevent extrinsic tooth stain formation. This study was a negative-controlled, randomized, two-period crossover design, with a 10-day washout period between treatments. The two treatments were a chewing gum containing 5.6% sodium hexametaphosphate and a negative control chewing gum. Eleven subjects who met study criteria were enrolled, and 10 completed the study over a two-week period. Each treatment period lasted approximately 48 hours and was separated by a washout period. After a dental prophylaxis, a digital image of the anterior teeth was taken to assess baseline stain. The three-day stain induction phase consisted of the patient using a 10 ml 0.2% chlorhexidine rinse for 60 seconds, followed by chewing two pellets/sticks of their assigned gum for five minutes and rinsing with 10 ml of cold tea solution for 60 seconds. No oral hygiene was permitted other than use of the test products. During both treatment periods, each subject followed the same regimen eight times, once per hour, throughout the day. On Days 2 and 3, the adjusted mean L* measurement was statistically significantly greater for the sodium hexametaphosphate gum than for the control gum. Moreover, nine of the 10 subjects had whiter teeth while on the experimental gum treatment at both Day 2 and Day 3. The results of this study support that sodium hexametaphosphate delivered from a chewing gum prevents dental stain formation and leads to a patient-desired whitening benefit.

Alternatives for reducing relapse rate when switching from natalizumab to fingolimod in multiple sclerosis.

PubMed

Fragoso, Yara Dadalti; Adoni, Tarso; Alves-Leon, Soniza Vieira; Apostolos-Pereira, Samira Luisa; Araujo, Yuna Ribeiro de; Becker, Jefferson; Brooks, Joseph Bruno Bidin; Correa, Eber Castro; Damasceno, Alfredo; Damasceno, Carlos Augusto de Albuquerque; Ferreira, Maria Lucia B; Gama, Paulo Diniz da; Gama, Rodrigo Assad Diniz da; Gomes, Sidney; Goncalves, Marcus Vinicius Magno; Grzesiuk, Anderson Kuntz; Machado, Suzana Costa Nunes; Matta, Andre Palma da Cunha; Mendes, Maria Fernanda; Ribeiro, Taysa Alexandrino Goncalves Jube; Rocha, Cristiane Franklin da; Ruocco, Heloisa Helena; Sato, Henry; Simm, Renata Faria; Tauil, Carlos Bernardo; Vasconcelos, Claudia Cristina Ferreira; Vieira, Vera Lucia Ferreira

2016-02-21

Natalizumab is a therapeutic option for treating multiple sclerosis (MS) and is particularly efficacious for patients with highly active disease. A long washout period has been recommended between withdrawal of natalizumab and start of fingolimod (another option for treating MS). This long washout period has been associated with a significant increase in MS activity. In the present study, a group of 96 patients who were switched from natalizumab to fingolimod had short washout periods between drugs, or monthly corticosteroid pulse therapy if longer washout periods were recommended. This therapeutic approach led to the lowest reported relapse rate so far, among patients with MS switching from natalizumab to fingolimod (8.3%). No complications from short withdrawal were observed in this group of patients.

Antihypertensive effect of alpha- and beta-adrenergic blockade in obese and lean hypertensive subjects.

PubMed

Wofford, M R; Anderson, D C; Brown, C A; Jones, D W; Miller, M E; Hall, J E

2001-07-01

The purpose of this study was to determine the contribution of the adrenergic system in mediating hypertension in obese and lean patients. Thirteen obese, hypertensive patients with a body mass index (BMI) > or =28 kg/m2 (obese) and nine lean patients with a BMI < or =25 kg/m2 (lean) were recruited. After a 1-week washout period, participants underwent daytime ambulatory blood pressure monitoring (ABPM). Participants were then treated with the alpha-adrenergic antagonist doxazosin, titrating to 4 mg QHS in 1 week. In the next week, the beta-adrenergic antagonist atenolol was added at an initial dose of 25 mg/day and titrated to 50 mg/day within 1 week. One month after the addition of atenolol, all patients underwent a second ABPM session. There were no differences between the obese and lean subjects in baseline systolic (SBP), diastolic (DBP), or mean arterial pressures (MAP) measured by office recording or ABPM. However, obese subjects had higher heart rates than lean subjects (87.5+/-2.4 v 76.8+/-4.9 beats/min). After 1 month of treatment with the adrenergic blockers, obese patients had a significantly lower SBP (130.0+/-2.5 v 138.9+/-2.1 mm Hg, P = .02) and MAP (99.6+/-2.3 v 107.0+/-1.5 mm Hg, P = .02) than lean patients. Obese patients also tended to have a lower DBP than lean patients (84.3+/-2.5 v 90.9+/-1.6 mm Hg, P = .057), but there was no significant difference in heart rate after 1 month of adrenergic blockade. These results indicate that blood pressure is more sensitive to adrenergic blockade in obese than in lean hypertensive patients and suggest that increased sympathetic activity may be an important factor in the maintenance of hypertension in obesity.

Effect of cement washout on loosening of abutment screws and vice versa in screw- and cement- retained implant-supported dental prosthesis

PubMed Central

Kim, Seok-Gyu; Son, Mee-Kyoung

2015-01-01

PURPOSE The purpose of this study was to examine the abutment screw stability of screw- and cement-retained implant-supported dental prosthesis (SCP) after simulated cement washout as well as the stability of SCP cements after complete loosening of abutment screws. MATERIALS AND METHODS Thirty-six titanium CAD/CAM-made implant prostheses were fabricated on two implants placed in the resin models. Each prosthesis is a two-unit SCP: one screw-retained and the other cemented. After evaluating the passive fit of each prosthesis, all implant prostheses were randomly divided into 3 groups: screwed and cemented SCP (Control), screwed and noncemented SCP (Group 1), unscrewed and cemented SCP (Group 2). Each prosthesis in Control and Group 1 was screwed and/or cemented, and the preloading reverse torque value (RTV) was evaluated. SCP in Group 2 was screwed and cemented, and then unscrewed (RTV=0) after the cement was set. After cyclic loading was applied, the postloading RTV was measured. RTV loss and decementation ratios were calculated for statistical analysis. RESULTS There was no significant difference in RTV loss ratio between Control and Group 1 (P=.16). No decemented prosthesis was found among Control and Group 2. CONCLUSION Within the limits of this in vitro study, the stabilities of SCP abutment screws and cement were not significantly changed after simulated cement washout or screw loosening. PMID:26140172

Results from Carbon Dioxide Washout Testing Using a Suited Manikin Test Apparatus with a Space Suit Ventilation Test Loop

NASA Technical Reports Server (NTRS)

Chullen, Cinda; Conger, Bruce; McMillin, Summer; Vonau, Walt; Kanne, Bryan; Korona, Adam; Swickrath, Mike

2016-01-01

NASA is developing an advanced portable life support system (PLSS) to meet the needs of a new NASA advanced space suit. The PLSS is one of the most critical aspects of the space suit providing the necessary oxygen, ventilation, and thermal protection for an astronaut performing a spacewalk. The ventilation subsystem in the PLSS must provide sufficient carbon dioxide (CO2) removal and ensure that the CO2 is washed away from the oronasal region of the astronaut. CO2 washout is a term used to describe the mechanism by which CO2 levels are controlled within the helmet to limit the concentration of CO2 inhaled by the astronaut. Accumulation of CO2 in the helmet or throughout the ventilation loop could cause the suited astronaut to experience hypercapnia (excessive carbon dioxide in the blood). A suited manikin test apparatus (SMTA) integrated with a space suit ventilation test loop was designed, developed, and assembled at NASA in order to experimentally validate adequate CO2 removal throughout the PLSS ventilation subsystem and to quantify CO2 washout performance under various conditions. The test results from this integrated system will be used to validate analytical models and augment human testing. This paper presents the system integration of the PLSS ventilation test loop with the SMTA including the newly developed regenerative Rapid Cycle Amine component used for CO2 removal and tidal breathing capability to emulate the human. The testing and analytical results of the integrated system are presented along with future work.

Bifurcations and chaos in a parametrically damped two-well Duffing oscillator subjected to symmetric periodic pulses.

PubMed

Chacón, R; Martínez García-Hoz, A

1999-06-01

We study a parametrically damped two-well Duffing oscillator, subjected to a periodic string of symmetric pulses. The order-chaos threshold when altering solely the width of the pulses is investigated theoretically through Melnikov analysis. We show analytically and numerically that most of the results appear independent of the particular wave form of the pulses provided that the transmitted impulse is the same. By using this property, the stability boundaries of the stationary solutions are determined to first approximation by means of an elliptic harmonic balance method. Finally, the bifurcation behavior at the stability boundaries is determined numerically.

Long-acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader-Willi syndrome.

PubMed

De Waele, Kathleen; Ishkanian, Stacey L; Bogarin, Roberto; Miranda, Charmaine A; Ghatei, Mohammad A; Bloom, Stephen R; Pacaud, Danièle; Chanoine, Jean-Pierre

2008-10-01

Ghrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not desacyl) ghrelin stimulates appetite. Both concentrations are elevated in Prader-Willi syndrome (PWS), suggesting that ghrelin may contribute to hyperphagia and overweight in these subjects. We evaluated whether long-acting octreotide (Oct) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS. A 56-week prospective, randomized, cross-over trial. Nine subjects with PWS (age 14.6 (10.8-18.9) years, body mass index (BMI) Z-score +1.9 (0.6-3.0)) received either Oct (30 mg) or saline i.m. every 4 weeks for 16 weeks and were switched over to the other treatment after a 24-week washout period. Eight subjects completed the study. Oct caused a decrease in both acylated (-53%) and desacyl (-54%) fasting ghrelin concentrations (P<0.05) but did not significantly affect BMI. Oct had no significant effect on peptide YY concentrations, appetite or compulsive behaviour towards food. Oct caused a decrease in insulin-like growth factor-I concentrations, an increase in HbA1c and transient elevation of blood glucose in two subjects. Three subjects developed gallstones. Oct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Future intervention studies aiming at clarifying the role of ghrelin in PWS should focus on the administration of specific inhibitors of ghrelin secretion or ghrelin receptor activity that do not interfere with other appetite-regulating peptides.

Modifying upper-limb inter-joint coordination in healthy subjects by training with a robotic exoskeleton.

PubMed

Proietti, Tommaso; Guigon, Emmanuel; Roby-Brami, Agnès; Jarrassé, Nathanaël

2017-06-12

). Adaptation was evidenced by a partial decrease of the movement deviations due to the fields, during the repetitions, but it occurred only on 21% of the motions. Nonetheless post-effects were observed in 86% of cases during the wash-out and follow up periods (right after the removal of the perturbation by the fields and after 30 minutes of being detached from the exoskeleton). Important inter-individual differences were observed but with small variability within subjects. In particular, a group of subjects showed an over-shoot with respect to the original unexposed trajectories (in 30% of cases), but the most frequent consequence (in 55% of cases) was the partial persistence of the modified upper-limb coordination, adopted at the time of the perturbation. Temporal and spatial generalizations were also evidenced by the deviation of the movement trajectories, both at the end-effector and at the intermediate joints and the modification of the final pointing postures towards targets which were never exposed to any field. Such results are the first quantified characterization of the effects of modification of the upper-limb coordination in healthy subjects, by imposing modification through viscous force fields distributed at the joint level, and could pave the way towards opportunities to rehabilitate pathological arm synergies with robots.

A single-dose, crossover, placebo- and moxifloxacin-controlled study to assess the effects of neratinib (HKI-272) on cardiac repolarization in healthy adult subjects.

PubMed

Hug, Bruce; Abbas, Richat; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl

2010-08-01

Neratinib is an orally administered, small-molecule, irreversible pan-ErbB inhibitor in development for the treatment of ErbB2-positive breast cancer. This study assessed the effects of therapeutic and supratherapeutic neratinib concentrations on cardiac repolarization, in accordance with current regulatory guidance. This was a two-part study in healthy subjects. In part 1, subjects were randomized to receive placebo, 400 mg moxifloxacin, or 240 mg neratinib (therapeutic dose) following a high-fat meal. In part 2, after a washout period, subjects received placebo plus 400 mg ketoconazole or 240 mg neratinib plus ketoconazole (supratherapeutic dose). ANOVA was used to compare the baseline-adjusted QTc interval for neratinib with that of placebo (reference), and for neratinib plus ketoconazole with that of placebo plus ketoconazole (reference). Pharmacokinetic/pharmacodynamic analyses and categorical summaries of interval data were done. Assay sensitivity was evaluated by the effect of moxifloxacin on QTc compared with placebo. Sixty healthy subjects were enrolled in this study. The upper bounds of the 90% confidence interval for baseline-adjusted QTcN (population-specific corrected QT) were subjects had QTcI, QTcF, or QTcN intervals >450 milliseconds or change from baseline >30 milliseconds. Moxifloxacin produced a significant increase in QTcN compared with placebo (P < 0.05). Therapeutic and supratherapeutic plasma concentrations of neratinib do not prolong the QTc interval in healthy subjects. (c) 2010 AACR.

Effects of food and grapefruit juice on single-dose pharmacokinetics of blonanserin in healthy Chinese subjects.

PubMed

Shang, De-Wei; Wang, Zhan-Zhang; Hu, Hai-Tang; Zhang, Yue-Feng; Ni, Xiao-Jia; Lu, Hao-Yang; Zhang, Ming; Hu, Jin-Qing; Qiu, Chang; Peng, Huan; Shen, Ling-Fang; Wen, Yu-Guan

2018-01-01

The purpose of this study was to investigate the potential effects of a meal and grapefruit juice on the pharmacokinetics of blonanserin and its metabolite N-desethyl blonanserin in healthy Chinese volunteers. This was a single-centre, open-label, fixed-sequence study, where 12 healthy Chinese volunteers received a single dose of 8 mg blonanserin after an overnight fast in period 1 (reference), a high-fat meal during period 2 and with co-administration of 250 mL of grapefruit juice in period 3. The washout period was 7 days. Series of plasma samples were collected after each dose to determine concentrations of blonanserin and its metabolite N-desethyl blonanserin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated by non-compartmental analysis and compared between periods by standard average bioequivalence ANOVA. Adverse events were monitored throughout the study. All subjects completed the study. High-fat meals significantly increased blonanserin exposure (AUC t ) 2.58-fold (90% CI 2.21, 3.02), relative to the reference period. Co-administration of blonanserin with grapefruit juice remarkably prolonged elimination half-life of blonanserin (from 9.7 to 21.4 h) and significantly increased exposures to blonanserin and N-desethyl blonanserin by 5.82-fold (90% CI 4.57, 7.42) and 1.81-fold (90% CI 1.65, 1.98), respectively. These results suggested that blonanserin was largely metabolised in the intestinal tract before becoming systemically available, and both food and grapefruit juice enhanced exposure to blonanserin and N-desethyl blonanserin. Grapefruit juice increased bioavailability and may have reduced systemic clearance of blonanserin. Further intestinal CYP3A4 and hepatic CYP3A4 might be postulated to explain the delayed elimination of blonanserin. Dose adjustment of blonanserin is needed on the basis of co-intake of known strong CYP3A4 inhibitor. Patients taking high-dose blonanserin also need to be cautious about

Impact of Software Settings on Multiple-Breath Washout Outcomes.

PubMed

Summermatter, Selina; Singer, Florian; Latzin, Philipp; Yammine, Sophie

2015-01-01

Multiple-breath washout (MBW) is an attractive test to assess ventilation inhomogeneity, a marker of peripheral lung disease. Standardization of MBW is hampered as little data exists on possible measurement bias. We aimed to identify potential sources of measurement bias based on MBW software settings. We used unprocessed data from nitrogen (N2) MBW (Exhalyzer D, Eco Medics AG) applied in 30 children aged 5-18 years: 10 with CF, 10 formerly preterm, and 10 healthy controls. This setup calculates the tracer gas N2 mainly from measured O2 and CO2concentrations. The following software settings for MBW signal processing were changed by at least 5 units or >10% in both directions or completely switched off: (i) environmental conditions, (ii) apparatus dead space, (iii) O2 and CO2 signal correction, and (iv) signal alignment (delay time). Primary outcome was the change in lung clearance index (LCI) compared to LCI calculated with the settings as recommended. A change in LCI exceeding 10% was considered relevant. Changes in both environmental and dead space settings resulted in uniform but modest LCI changes and exceeded >10% in only two measurements. Changes in signal alignment and O2 signal correction had the most relevant impact on LCI. Decrease of O2 delay time by 40 ms (7%) lead to a mean LCI increase of 12%, with >10% LCI change in 60% of the children. Increase of O2 delay time by 40 ms resulted in mean LCI decrease of 9% with LCI changing >10% in 43% of the children. Accurate LCI results depend crucially on signal processing settings in MBW software. Especially correct signal delay times are possible sources of incorrect LCI measurements. Algorithms of signal processing and signal alignment should thus be optimized to avoid susceptibility of MBW measurements to this significant measurement bias.

The acute and temporary modulation of PERIOD genes by hydrocortisone in healthy subjects.

PubMed

Yurtsever, Türkan; Schilling, Thomas M; Kölsch, Monika; Turner, Jonathan D; Meyer, Jobst; Schächinger, Hartmut; Schote, Andrea B

2016-01-01

The physiological stress system and the circadian clock system communicate with each other at different signaling levels. The steroid hormone cortisol, the end-effector of the hypothalamus-pituitary-adrenal axis, is released in response to stress and acts as a mediator in circadian rhythms. We determined the effect of escalating cortisol doses on the expression of PERIOD genes (PER1, PER2 and PER3) in healthy subjects and analyzed whether the glucocorticoid receptor (GR) is involved in the cortisol-mediated PERIOD gene expression. Forty participants (50% males and 50% females) were randomly assigned to groups receiving a saline placebo solution or 3 mg, 6 mg, 12 mg and 24 mg of hydrocortisone. Blood was drawn every 15 min to measure quantitative gene expression of PER1, PER2 and PER3. A potential role of the GR was determined by an ex vivo study stimulating whole blood with hydrocortisone and RU486 (a GR antagonist). As a result, moderate doses of hydrocortisone produced an acute and temporary induction of PER1 and PER3 mRNA levels, whereas PER2 was not responsive to the hormone administration. The cortisol-dependent induction of PER1 was blocked by the GR antagonist in whole blood after treatment with hydrocortisone and RU486 ex vivo. In conclusion, acute pharmacological stress modulated the expression of PER1 and PER3 in whole blood temporarily in our short-term sampling design, suggesting that these circadian genes mediate stable molecular mechanisms in the periphery.

A 2-night, 3-period, crossover study of ramelteon's efficacy and safety in older adults with chronic insomnia.

PubMed

Roth, Thomas; Seiden, David; Wang-Weigand, Sherry; Zhang, Jeffrey

2007-05-01

To assess the efficacy and safety of ramelteon, a selective melatonin MT1/MT2-receptor agonist, for insomnia treatment in older adults. In a randomized, 9-week, 3-period crossover trial conducted at 17 sleep centers, older adults (N = 100) with chronic primary insomnia (37 men, 63 women; mean age [range], 70.7 [65-83] years) were administered placebo, ramelteon 4 mg, and ramelteon 8 mg in three treatment phases for two consecutive nights. Each phase was separated by 5- to 12-day washout periods. Sleep was monitored via polysomnography. Subjective sleep parameters, using a Postsleep Questionnaire, were recorded, and residual pharmacologic effects were assessed. Statistically significant reductions in latency to persistent sleep were observed with both ramelteon 4 mg and 8 mg compared to placebo (28.7 min vs. 38.4 min, p < 0.001; 30.8 min vs. 38.4 min, p = 0.005, respectively). Total sleep time (p = 0.036 and p = 0.007, respectively) and sleep efficiency (p = 0.037 and p = 0.007, respectively) were also significantly improved with ramelteon 4 mg and 8 mg compared to placebo. Statistically significant reductions in subjective sleep latency on a Postsleep Questionnaire were reported with ramelteon 4 mg versus placebo (p = 0.037), but not ramelteon 8 mg (p = 0.120); no significant differences on other subjective sleep assessments were reported. A lack of power limits interpretation of self-reported sleep parameters. Incidences of adverse events considered treatment related were placebo (7%), ramelteon 4 mg (11%), and ramelteon 8 mg (5%). No residual pharmacologic effects were observed via Digit Symbol Substitution Test, memory recall tests (immediate and delayed), visual analog scales (feelings and mood), and Postsleep Questionnaire (level of alertness and ability to concentrate). In older adults with chronic primary insomnia, ramelteon produced significant reductions in latency to persistent sleep and increases in total sleep time and sleep efficacy, and showed no

Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A.

PubMed

Coyle, T E; Reding, M T; Lin, J C; Michaels, L A; Shah, A; Powell, J

2014-04-01

BAY 94-9027 is a B-domain-deleted recombinant factor VIII (rFVIII) with site-specific attachment of poly(ethylene glycol) that has shown an extended half-life in animal models of hemophilia. To assess the pharmacokinetics and safety of BAY 94-9027 after single and repeated administration in subjects with severe hemophilia A. This 8-week, prospective, multicenter, open-label, phase I trial was conducted in 14 subjects aged 21–58 years with FVIII of < 1%, ≥ 150 days of exposure to FVIII, and no history of FVIII inhibitors. After a ≥ 3-day washout, subjects received a single dose of sucrose-formulated rFVIII (rFVIII-FS) (cohort 1 [n = 7], 25 IU kg−1; cohort 2 [n = 7], 50 IU kg−1) for a 48-h pharmacokinetic (PK) study. After another ≥ 3-day washout, cohort 1 received twice-weekly BAY 94-9027 at 25 IU kg−1 (16 doses), and cohort 2 received once-weekly BAY 94-9027 at 60 IU kg−1 (nine doses). A 168-h PK study was performed after the first and last BAY 94-9027 doses. BAY 94-9027 showed equivalent recovery and an improved PK profile vs. rFVIII-FS, with a half-life of ~ 19 h (vs. ~ 13.0 h for rFVIII-FS). BAY 94-9027 was well tolerated, and no immunogenicity was observed. This phase I study demonstrates that BAY 94-9027 has an extended half-life in subjects with hemophilia A and, after multiple dosing, was well tolerated with no immunogenicity during the 8-week trial. A phase III study in a larger number of subjects is underway to fully characterize how this prolonged half-life will permit less frequent prophylaxis dosing for patients with hemophilia.

Comparison of low-abundance biomarker levels in capillary-collected nonstimulated tears and washout tears of aqueous-deficient and normal patients.

PubMed

Guyette, Nicole; Williams, Larezia; Tran, My-Tho; Than, Tammy; Bradley, John; Kehinde, Lucy; Edwards, Clara; Beasley, Mark; Fullard, Roderick

2013-05-01

Low tear volume limits the use of nonstimulated (NS) microcapillary tear collection in aqueous-deficient (AD) patients. Adding a small amount of "washout" fluid to the eye prior to tear collection is a potentially viable alternative method for abundant proteins, but is relatively untested for low-abundance biomarkers. This study determined the feasibility of the washout (WO) method as an NS alternative for low-abundance biomarkers. NS and WO biomarker profiles were compared between AD patients and non-AD controls to determine if the two methods identify the same intergroup differences. Matching NS and WO tears were collected from 48 patients by micropipette, the WO sample after instillation of 10 μL saline. Tear cytokine levels were measured by 27-Plex Bio-Rad assay. Bland-Altman analyses for each biomarker determined the agreement between tear sample types. Patients were grouped as AD or non-AD based on Schirmer score to determine if NS profile between-group differences were preserved in WO tears. Bland-Altman plots showed good biomarker level agreement between NS and WO tears for most cytokines. Five biomarkers, among those most often cited as differing in AD dry eye, differed significantly between non-AD and AD groups in both tear types. Additional biomarker differences were seen in NS tears only. The WO tear collection method is a viable alternative to NS tears for many low-abundance biomarkers and is able to replicate major NS tear differences between dry eye groups. More subtle intergroup differences are lost in WO samples because of reduced statistical power.

TOPIRAMATE’S EFFECTS ON COCAINE-INDUCED SUBJECTIVE MOOD, CRAVING, AND PREFERENCE FOR MONEY OVER DRUG TAKING

PubMed Central

Johnson, Bankole A.; Roache, John D.; Ait-Daoud, Nassima; Gunderson, Erik W.; Haughey, Heather M.; Wang, Xin-Qun; Liu, Lei

2012-01-01

Topiramate, presumably through antagonism of excitatory glutaminergic pathways and facilitation of inhibitory gamma-aminobutyric acid neurons in the cortico-mesolimbic system, might reduce cocaine’s abuse liability. We tested whether topiramate (100 mg twice daily) would reduce the euphoria, subjective mood, craving, and preference for cocaine over money induced by low and high doses (0.325 and 0.650 mg/kg i.v., respectively) of experimentally administered cocaine in 24 male and female, cocaine-dependent, non-treatment-seeking research volunteers in a university inpatient laboratory. We utilized a randomized, double-blind, placebo-controlled, within-subject, Latin-square crossover design in which 3 experimental challenge doses of low-dose cocaine, high-dose cocaine, and placebo were administered in counterbalanced order after 5 days of topiramate or matching placebo pretreatments separated by a 1-week washout period (2006–2009). After placebo pretreatments, cocaine produced dose-related increases in euphoria, stimulant effects, craving for more cocaine, and monetary value of cocaine in a behavioral preference test of cocaine vs. money choice. Topiramate pretreatment reduced the cocaine-related craving and monetary value of high-dose cocaine while increasing the monetary value, euphoria, and stimulant effects of low-dose cocaine. Validated and standardized human experimental methods evaluating the potential for topiramate to alter cocaine’s abuse liability suggest that topiramate may reduce the reinforcing effects and craving induced by higher cocaine doses. Low-dose cocaine might appear to have some enhancement of its stimulant properties in the presence of topiramate’s prominent sedative effects. PMID:23039088

Treadmill training with partial body weight support compared with conventional gait training for low-functioning children and adolescents with nonspastic cerebral palsy: a two-period crossover study.

PubMed

Su, Ivan Y W; Chung, Kenny K Y; Chow, Daniel H K

2013-12-01

Partial body weight-supported treadmill training has been shown to be effective in gait training for patients with neurological disorders such as spinal cord injuries and stroke. Recent applications on children with cerebral palsy were reported, mostly on spastic cerebral palsy with single subject design. There is lack of evidence on the effectiveness of such training for nonspastic cerebral palsy, particularly those who are low functioning with limited intellectual capacity. This study evaluated the effectiveness of partial body weight-supported treadmill training for improving gross motor skills among these clients. A two-period randomized crossover design with repeated measures. A crossover design following an A-B versus a B-A pattern was adopted. The two training periods consisted of 12-week partial body weight-supported treadmill training (Training A) and 12-week conventional gait training (Training B) with a 10-week washout in between. Ten school-age participants with nonspastic cerebral palsy and severe mental retardation were recruited. The Gross Motor Function Measure-66 was administered immediately before and after each training period. Significant improvements in dimensions D and E of the Gross Motor Function Measure-66 and the Gross Motor Ability Estimator were obtained. Our findings revealed that the partial body weight-supported treadmill training was effective in improving gross motor skills for low-functioning children and adolescents with nonspastic cerebral palsy. .

Long-term titrated IOP control with one, two, or three trabecular micro-bypass stents in open-angle glaucoma subjects on topical hypotensive medication: 42-month outcomes

PubMed Central

Erb, Carl; Carceller Guillamet, Amadeu; Fea, Antonio M; Voskanyan, Lilit; Giamporcaro, Jane Ellen; Hornbeak, Dana M

2018-01-01

Purpose Evaluate long-term outcomes after one, two, or three trabecular micro-bypass stents implanted in a standalone procedure in eyes with open-angle glaucoma taking ocular hypotensive medication. Patients and methods Prospective randomized ongoing study of 119 subjects (109 with 42-month follow-up) with open-angle glaucoma, preoperative intraocular pressure (IOP) 18–30 mmHg on one to three glaucoma medications, and unmedicated (post-washout) IOP 22–38 mmHg. Subjects were randomized to receive one (n=38), two (n=41), or three (n=40) iStent trabecular micro-bypass stents in a standalone procedure. Postoperatively, IOP was measured with medication and annually following washout. Data included IOP, medications, gonioscopy, pachymetry, visual field, visual acuity, adverse events, and slit-lamp and fundus examinations. Results Preoperative mean medicated IOP was 19.8±1.3 mmHg on 1.71 medications in one-stent eyes, 20.1±1.6 mmHg on 1.76 medications in two-stent eyes, and 20.4±1.8 mmHg on 1.53 medications in three-stent eyes. Post-washout IOP prior to stent implantation was 25.0±1.2, 25.0±1.7, and 25.1±1.9 mmHg in the three groups, respectively. Postoperatively, Month 42 medicated IOP was 15.0±2.8, 15.7±1.0 and 14.8±1.3 mmHg in the three groups, and post-washout IOP (Months 36–37) was 17.4±0.9, 15.8±1.1 and 14.2±1.5 mmHg, respectively. IOP reduction ≥20% without medication was achieved in 89%, 90%, and 92% of one-, two-, and three-stent eyes, respectively, at Month 12; and in 61%, 91%, and 91% of eyes, respectively, at Month 42. The need for additional medication remained consistent at Months 12 and 42 in multi-stent eyes (four two-stent eyes and three three-stent eyes at both time points), whereas it increased in single-stent eyes (four eyes at Month 12 versus 18 eyes at Month 42). Safety parameters were favorable in all groups. Conclusion The standalone implantation of either single or multiple iStent® device(s) produced safe, clinically

Studies on the bioavailability of the provitamin A carotenoid, beta-carotene, using human exfoliated colonic epithelial cells.

PubMed

Gireesh, T; Nair, P P; Sudhakaran, P R

2004-08-01

The possibility of using exfoliated colonic epithelial cells for assessing the bioavailability of beta-carotene was examined. Analysis of exfoliated colonic epithelial cells showed the presence of beta-carotene and vitamin A. The beta-carotene content was significantly lower in cells from stool samples of subjects on a beta-carotene-poor diet than those receiving a single dose of a beta-carotene supplement. Colonic epithelial cells isolated from stool samples collected daily during a wash-out period while the subjects were on a beta-carotene-poor diet showed a steady decrease in beta-carotene content, reaching the lowest value on day 7. Kinetic analysis showed that a single dose of a beta-carotene supplement in the form of spirulina (Spirulina platensis) or agathi (Sesbania grandiflora) after the wash-out period caused an increase in the beta-carotene content after a lag period of 5-7 d, but the vitamin A levels during these periods were not significantly affected. Analysis of plasma beta-carotene concentration also showed similar changes, which correlated with those of exfoliated colonic cells. A relationship between the beta-carotene content of the diet and that of the colonic epithelial cells suggests that analysis of the beta-carotene content in exfoliated human colonic epithelial cells is a useful non-invasive method to assess the bioavailability of provitamin A beta-carotene.

Relative bioavailability of tizanidine hydrochloride capsule formulation compared with capsule contents administered in applesauce: a single-dose, open-label, randomized, two-way, crossover study in fasted healthy adult subjects.

PubMed

Henney, Herbert R; Fitzpatrick, Anthony; Stewart, Johnston; Runyan, Jacob D

2008-12-01

The alpha2-adrenergic agonist tizanidine has been reported to have a narrow therapeutic index. A multiparticulate capsule formulation of tizanidine has been developed in an attempt to improve patient tolerability. This study assessed bioequivalence between a single, intact, 6-mg capsule of tizanidine and the capsule contents sprinkled in applesauce in fasted healthy subjects. Healthy male and female subjects aged 18 to 45 years completed 2 treatment periods: one with a tizanidine 6-mg capsule administered intact and the other with capsule contents sprinkled in applesauce. The 2 treatment periods had a 6-day washout period between administrations. Plasma tizanidine concentrations were determined for blood samples collected over 24 hours after administration. All treatment-emergent adverse events were recorded and graded by intensity and relationship to the study drug (not, improbable, possible, probable, definite) by the attending physician based on his or her clinical impression. A total of 19 men and 9 women (mean age, 26 years) completed the trial. Geometric mean natural logarithm-transformed AUC values (AUC(0-infinity) [AUC to infinity] and AUC(0-t) [AUC to the last measurable time point]) and C(max) ratios were significantly (P subjects (61%), including 15 subjects (54%) with the intact capsule reporting 18 events and 11 subjects (39%) with the sprinkled contents reporting 13 events. No serious adverse events or deaths were reported, and no subjects were discontinued due to adverse events. The contents of the tizanidine capsule sprinkled in applesauce were not bioequivalent to the intact 6-mg capsule in these fasted healthy

Bayesian modelling of lung function data from multiple-breath washout tests.

PubMed

Mahar, Robert K; Carlin, John B; Ranganathan, Sarath; Ponsonby, Anne-Louise; Vuillermin, Peter; Vukcevic, Damjan

2018-05-30

Paediatric respiratory researchers have widely adopted the multiple-breath washout (MBW) test because it allows assessment of lung function in unsedated infants and is well suited to longitudinal studies of lung development and disease. However, a substantial proportion of MBW tests in infants fail current acceptability criteria. We hypothesised that a model-based approach to analysing the data, in place of traditional simple empirical summaries, would enable more efficient use of these tests. We therefore developed a novel statistical model for infant MBW data and applied it to 1197 tests from 432 individuals from a large birth cohort study. We focus on Bayesian estimation of the lung clearance index, the most commonly used summary of lung function from MBW tests. Our results show that the model provides an excellent fit to the data and shed further light on statistical properties of the standard empirical approach. Furthermore, the modelling approach enables the lung clearance index to be estimated by using tests with different degrees of completeness, something not possible with the standard approach. Our model therefore allows previously unused data to be used rather than discarded, as well as routine use of shorter tests without significant loss of precision. Beyond our specific application, our work illustrates a number of important aspects of Bayesian modelling in practice, such as the importance of hierarchical specifications to account for repeated measurements and the value of model checking via posterior predictive distributions. Copyright © 2018 John Wiley & Sons, Ltd.

Lack of a Pharmacokinetic Interaction Between Saxagliptin and Dapagliflozin in Healthy Subjects: A Randomized Crossover Study.

PubMed

Vakkalagadda, Blisse; Lubin, Susan; Reynolds, Laurie; Liang, Dan; Marion, Alan S; LaCreta, Frank; Boulton, David W

2016-08-01

This single-dose, open-label, randomized, 3-period, 3-treatment crossover drug-drug interaction study was conducted to evaluate differences in the pharmacokinetic properties of saxagliptin and dapagliflozin when coadministered. Healthy subjects (N = 42) were randomized to receive saxagliptin 5 mg alone, dapagliflozin 10 mg alone, or saxagliptin 5 mg plus dapagliflozin 10 mg coadministered; there was a washout period of ≥6 days between treatments. Serial blood samples for determining saxagliptin, 5-hydroxy saxagliptin (5-OH saxagliptin; major active metabolite) and dapagliflozin plasma concentrations and pharmacokinetic parameters were collected before and up to 60 hours after the dose. No interaction was to be concluded if the 90% CIs for the geometric mean ratios of the combination compared with each drug given alone for Cmax and AUCinf were within 0.80 to 1.25. The results indicated that dapagliflozin had no effect on the pharmacokinetic properties of saxagliptin, 5-OH saxagliptin, or saxagliptin total active moiety and vice versa. The 90% CIs for Cmax and AUCinf for all comparisons were contained entirely within the 0.80 to 1.25 equivalence intervals. Other pharmacokinetic parameters (apparent oral clearance or half-life) of saxagliptin or dapagliflozin were similar when each medicine was administered alone or when coadministered. No safety profile or tolerability findings of concern were observed during the study. All adverse events were mild, and no serious adverse events were reported. These data indicate that coadministration of saxagliptin and dapagliflozin exhibits no pharmacokinetic interaction and is well tolerated. ClinicalTrials.gov identifier: NCT01662999. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Effect of oral glycine on the clinical, spirometric and inflammatory status in subjects with cystic fibrosis: a pilot randomized trial.

PubMed

Vargas, Mario H; Del-Razo-Rodríguez, Rosangela; López-García, Amando; Lezana-Fernández, José Luis; Chávez, Jaime; Furuya, María E Y; Marín-Santana, Juan Carlos

2017-12-15

Patients with cystic fibrosis (CF) have airway inflammation that contributes to symptoms and to pulmonary function derangement. Current drugs used to diminish airway inflammation improve the clinical and spirometric status of patients with CF, but their use is limited due to their undesired side effects, for example, glucose intolerance, growth retardation, and cataracts with corticosteroids, gastrointestinal toxicity with ibuprofen, and macrolide resistance with azythromycin. Glycine is known to decrease activation of inflammatory cells, including alveolar macrophages and neutrophils, and is relatively inexpensive, palatable, and virtually devoid of untoward effects. These features make glycine a good candidate for antiinflammatory treatment of CF. Thus, we aimed to explore whether glycine can exert a beneficial effect in a population of patients with CF. This was a randomized, double blinded, cross-over pilot clinical trial. Subjects with CF received, in random order, oral glycine (0.5 g/kg/day, dissolved in any liquid) and placebo (glass sugar), each during 8 weeks with an intermediate 2-week wash-out period. Thirteen subjects aged 6-23 years, 8 females, completed the two arms of the study. As compared with placebo, after glycine intake patients had better symptom questionnaire scores (p = 0.02), mainly regarding sputum features and dyspnea. While spirometric variables tended to decline during placebo intake, they remained stable or even increased during glycine treatment (p = 0.04 to p = 0.003). In this context, FEV 1 declined 8.6% after placebo and increased 9.7% at the end of the glycine period. Pulse oximetry improved after glycine intake (p = 0.04 vs. placebo). TNF-α in serum and IL-6 and G-CSF in sputum tended to decline at the end of the glycine period (p = 0.061, p = 0.068 and p = 0.04, respectively, vs placebo). Glycine was remarkably well tolerated. The clinical, spirometric and inflammatory status of subjects with CF

Auditory attention and multiattribute decision-making during a 33 h sleep-deprivation period: mean performance and between-subject dispersions.

PubMed

Linde, L; Edland, A; Bergström, M

1999-05-01

One purpose of this study was to compare attention in the evening (22:00 h), in the late night (04:00 h), in the morning (10:00 h) and in the afternoon (16:00 h) during a period of complete wakefulness beginning at 08:00 h with a mean daytime performance without sleep deprivation. Another purpose was to investigate sleep deprivation effects on a multi-attribute decision-making task with and without time pressure. Twelve sleep-deprived male students were compared with 12 male non-sleep-deprived students. Both groups were tested five times with an auditory attention and a symbol coding task. Significant declines (p < 0.05) in mean level of performance on the auditory attention task were found at 04:00, 10:00 and 16:00 h for subjects forced to the vigil. However, the effect of the sleep deprivation manifested itself even more in increased between-subject dispersions. There were no differences between time pressure and no time pressure on the decision-making task and no significant differences between sleep-deprived and non-sleep-deprived subjects in decision strategies. In fact, the pattern of decision strategies among the sleep-deprived subject was more similar to a pattern of decision strategies typical for non-stressful conditions than the pattern of decision strategies among the non-sleep-deprived subjects. This result may have been due to the fact that the sleep loss acted as a dearouser. Here too, however, the variances differed significantly among sleep-deprived and non-sleep-deprived subjects, indicating that the sleep-deprived subjects were more variable in their decision strategy pattern than the control group.

Reversal of apixaban anticoagulation by four-factor prothrombin complex concentrates in healthy subjects: a randomized three-period crossover study.

PubMed

Song, Y; Wang, Z; Perlstein, I; Wang, J; LaCreta, F; Frost, R J A; Frost, C

2017-11-01

Essentials Prothrombin complex concentrates (PCCs) may reverse the effect of factor Xa (FXa) inhibitors. We conducted an open-label, randomized, placebo-controlled, three-period crossover study in 15 subjects. Both PCCs rapidly reversed apixaban-mediated decreases in mean endogenous thrombin potential. Four-factor PCC administration had no effect on apixaban pharmacokinetics or anti-FXa activity. Background Currently, there is no approved reversal agent for direct activated factor Xa (FXa) inhibitors; however, several agents are under investigation, including prothrombin complex concentrates (PCCs). Objective This open-label, randomized, placebo-controlled, three-period crossover study assessed the effect of two four-factor PCCs on apixaban pharmacodynamics and pharmacokinetics in 15 healthy subjects. Methods Subjects received apixaban 10 mg twice daily for 3 days. On day 4, 3 h after apixaban, subjects received a 30-min infusion of 50 IU kg -1 Cofact, Beriplex P/N (Beriplex), or saline. Change in endogenous thrombin potential (ETP), measured with a thrombin generation assay (TGA), was the primary endpoint. Secondary endpoints included changes in other TGA parameters, prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time, anti-FXa activity, apixaban pharmacokinetics, and safety. Results Apixaban-related changes in ETP and several other pharmacodynamic measures occurred following apixaban administration. Both PCCs reversed apixaban's effect on ETP; the differences in adjusted mean change from pre-PCC baseline to end of infusion were 425 nm min (95% confidence interval [CI] 219.8-630.7 nm min; P < 0.001) for Cofact, and 91 nm min (95% CI - 31.3 to 212.4 nm min; P > 0.05) for Beriplex. Both PCCs returned ETP to pre-apixaban baseline levels 4 h after PCC infusion, versus 45 h for placebo. For both PCCs, mean ETP peaked 21 h after PCC initiation, and then slowly decreased over the following 48 h. Both PCCs reversed apixaban

Prospective, randomized study of one, two, or three trabecular bypass stents in open-angle glaucoma subjects on topical hypotensive medication

PubMed Central

Katz, L Jay; Erb, Carl; Carceller, Guillamet Amadeu; Fea, Antonio M; Voskanyan, Lilit; Wells, Jeffrey M; Giamporcaro, Jane Ellen

2015-01-01

Purpose To assess the safety and efficacy of one, two, or three trabecular microbypass stents in eyes with primary open-angle glaucoma (OAG) not controlled on ocular hypotensive medication. A total of 119 subjects were followed for 18 months postoperatively. Materials and methods Subjects with medicated intraocular pressure (IOP) 18–30 mmHg and postmedication-washout baseline IOP 22–38 mmHg were randomized to implantation of one, two, or three stents. Ocular hypotensive medication was to be used if postoperative IOP exceeded 18 mmHg. Results A total of 38 subjects were implanted with one stent, 41 subjects with two stents, and 40 subjects with three stents. Both month 12 IOP reduction ≥20% without ocular hypotensive medication vs baseline unmedicated IOP and month 12 unmedicated IOP ≤18 mmHg were achieved by 89.2%, 90.2%, and 92.1% of one-, two-, and three-stent eyes, respectively. Furthermore, 64.9%, 85.4%, and 92.1% of the three respective groups achieved unmedicated IOP ≤15 mmHg. Over the 18-month follow-up period, medication was required in seven one-stent subjects, four two-stent subjects, and three three-stent subjects. At 18 months, mean unmedicated IOP was 15.9±0.9 mmHg in one-stent subjects, 14.1±1.0 mmHg in two-stent subjects, and 12.2±1.1 mmHg in three-stent subjects. Month 18 IOP reduction was significantly greater (P<0.001) with implantation of each additional stent, with mean differences in reduction of 1.84 mmHg (95% confidence interval 0.96–2.73) for three-stent vs two-stent groups and 1.73 mmHg (95% confidence interval 0.83–2.64) for two-stent vs one-stent groups. Adverse events through 18 months were limited to cataract progression with best-corrected visual acuity loss and subsequent cataract surgery. Conclusion In this series, implantation of each additional stent resulted in significantly greater IOP reduction with reduced medication use. Titratability of stents as a sole procedure was shown to be effective and safe, with

Percutaneous debridement and washout of walled-off abdominal abscess and necrosis using flexible endoscopy: a large single-center experience.

PubMed

Mathers, Bradley; Moyer, Matthew; Mathew, Abraham; Dye, Charles; Levenick, John; Gusani, Niraj; Dougherty-Hamod, Brandy; McGarrity, Thomas

2016-01-01

Direct percutaneous endoscopic necrosectomy has been described as a minimally invasive intervention for the debridement of walled-off pancreatic necrosis (WOPN). In this retrospective cohort study, we aimed to confirm these findings in a US referral center and evaluate the clinical value of this modality in the treatment of pancreatic necrosis as well as other types of intra-abdominal fluid collections and necrosis. Twelve consecutive patients with WOPN or other abdominal abscess requiring debridement and washout underwent computed tomography (CT)-guided drainage catheter placement. Each patient then underwent direct percutaneous endoscopic necrosectomy and washout with repeat debridement performed until complete. Drains were then removed once output fell below 30 mL/day and imaging confirmed resolution. The primary endpoints were time to clinical resolution and sustained resolution at 1-year follow up.  Ten patients were treated for WOPN, one for necrotic hepatic abscesses, and one for omental necrosis. The median time to intervention was 85 days with an average of 2.3 necrosectomies performed. Complete removal of drains was accomplished in 11 patients (92 %). The median time to resolution was 57 days. No serious adverse events occurred; however, one patient developed pancreaticocutaneous fistulas. Ten patients completed 1-year surveillance of which none required drain replacement. No patients required surgery or repeat endoscopy. This series supports the premise that direct percutaneous endoscopic necrosectomy is a safe and effective intervention for intra-abdominal fluid collections and necrosis in appropriately selected patients. Our study demonstrates a high clinical success rate with minimal adverse events. This modality offers several potential advantages over surgical and transgastric approaches including use of improved accessibility, an excellent safety profile, and requirement for only deep or moderate sedation.

A novel sidestream ultrasonic flow sensor for multiple breath washout in children.

PubMed

Fuchs, Susanne I; Sturz, J; Junge, S; Ballmann, M; Gappa, M

2008-08-01

Inert gas multiple breath washout (MBW) for measuring Lung Clearance Index using mass spectrometry and 4% sulfur hexafluoride (SF(6)) as the tracer gas has been shown to be sensitive for detecting early Cystic Fibrosis (CF) lung disease. However, mass spectrometry requires bulky equipment and is expensive to buy and maintain. A novel sidestream ultrasonic device may overcome this problem. The aims of this study were to assess the feasibility and clinical validity of measuring lung volume (functional residual capacity, FRC) and the LCI using the sidestream ultrasonic flow sensor in children and adolescents with CF in relation to spirometry and plain chest radiographs. MBW using the sidestream ultrasonic device and conventional spirometry were performed in 26 patients with CF and 22 healthy controls. In the controls (4.7-17.7 years) LCI was similar to that reported using mass spectrometry (mean (SD) 6.7 (0.5)). LCI was elevated in 77% of the CF children (6.8-18.9 years), whereas spirometry was abnormal in only 38.5%, 61.5%, and 26.9% for FEV(1), MEF(25), and FEV(1)/FVC, respectively. This was more marked in children <10 years. LCI correlated with the Crispin-Norman score, whereas FEV(1) did not. Sidestream ultrasonic MBW is a valid and simple alternative to mass spectrometry for assessing ventilation homogeneity in children. (c) 2008 Wiley-Liss, Inc.

The in vitro antibiotic release from anti-washout apatite cement using chitosan.

PubMed

Takechi, Masaaki; Miyamoto, Youji; Momota, Yukihiro; Yuasa, Tetsuya; Tatehara, Seikou; Nagayama, Masaru; Ishikawa, Kunio; Suzuki, Kazuomi

2002-10-01

The in vitro antibiotic release from anti-washout apatite cement using chitosan (aw-AC(chi)) was investigated in a preliminary evaluation. Flomoxef sodium was employed as the antibiotic and was incorporated into the powder phase aw-AC(chi) at up to 10%. The setting times were measured for aw-AC(chi) containing various amounts of flomoxef sodium. X-ray diffraction (XRD) analysis was also conducted for the identification of products. To evaluate the drug release profile, set aw-AC was immersed in saline and the released flomoxef sodium was determined at regular intervals. The setting time was prolonged slightly with the addition of flomoxef sodium. The difference at 10% flomoxef sodium (0% vs. 10%) was not significant (p>0.05), and can be negligible in clinic. The XRD analysis revealed that formation of hydroxyapatite (HAP) from aw-AC(chi) was reduced, even after 24 h, when the aw-AC(chi) contained flomoxef sodium at 8% or more. The flomoxef sodium release from aw-AC(chi) showed the typical profile observed in skeleton type drug delivery system (DDS). Changing the concentration of chitosan can control the rate of drug release from aw-AC. Therefore, we conclude that aw-AC(chi) is a good candidate for potential use as a DDS carrier that may be useful in surgical operations.

Topiramate's effects on cocaine-induced subjective mood, craving and preference for money over drug taking.

PubMed

Johnson, Bankole A; Roache, John D; Ait-Daoud, Nassima; Gunderson, Erik W; Haughey, Heather M; Wang, Xin-Qun; Liu, Lei

2013-05-01

Topiramate, presumably through antagonism of excitatory glutaminergic pathways and facilitation of inhibitory gamma-aminobutyric acid neurons in the cortico-mesolimbic system, might reduce cocaine's abuse liability. We tested whether topiramate (100 mg twice daily) would reduce the euphoria, subjective mood, craving and preference for cocaine over money induced by low and high doses (0.325 and 0.65 mg/kg i.v., respectively) of experimentally administered cocaine in 24 male and female, cocaine-dependent, non-treatment-seeking research volunteers in a university in-patient laboratory. We utilized a randomized, double-blind, placebo-controlled, within-subject, Latin-square cross-over design in which three experimental challenge doses of low-dose cocaine, high-dose cocaine and placebo were administered in counterbalanced order after 5 days of topiramate or matching placebo pre-treatments separated by a 1-week washout period (2006-2009). After placebo pre-treatments, cocaine produced dose-related increases in euphoria, stimulant effects, craving for more cocaine and monetary value of cocaine in a behavioral preference test of cocaine versus money choice. Topiramate pre-treatment reduced the cocaine-related craving and monetary value of high-dose cocaine while increasing the monetary value, euphoria and stimulant effects of low-dose cocaine. Validated and standardized human experimental methods evaluating the potential for topiramate to alter cocaine's abuse liability suggest that topiramate may reduce the reinforcing effects and craving induced by higher cocaine doses. Low-dose cocaine might appear to have some enhancement of its stimulant properties in the presence of topiramate's prominent sedative effects. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

Antihypertensive effect of low-frequency transcutaneous electrical nerve stimulation (TENS) in comparison with drug treatment.

PubMed

Silverdal, Jonas; Mourtzinis, Georgios; Stener-Victorin, Elisabet; Mannheimer, Clas; Manhem, Karin

2012-10-01

Hypertension is a major risk factor for vascular disease, yet blood pressure (BP) control is unsatisfactory low, partly due to side-effects. Transcutaneous electrical nerve stimulation (TENS) is well tolerated and studies have demonstrated BP reduction. In this study, we compared the BP lowering effect of 2.5 mg felodipin once daily with 30 min of bidaily low-frequency TENS in 32 adult hypertensive subjects (mean office BP 152.7/90.0 mmHg) in a randomized, crossover design. Office BP and 24-h ambulatory BP monitoring (ABPM) were performed at baseline and at the end of each 4-week treatment and washout period. Felodipin reduced office BP by 10/6 mmHg (p <0.001 respectively) and after washout BP rose to a level still significantly lower than at baseline. TENS reduced office BP by 5/1.5 mmHg (p <0.01, ns). After TENS washout, BP was further reduced and significantly lower than at baseline, but at levels similar to BP after felodipin washout and therefore reasonably caused by factors other than the treatment per se. ABPM revealed a significant systolic reduction of 3 mmHg by felodipin, but no significant changes were noted after TENS. We conclude that our study does not present any solid evidence of BP reduction of TENS.

Revisioning fat lesbian subjects in contemporary lesbian periodicals.

PubMed

Snider, Stefanie

2010-01-01

It is difficult to find a visual representation of any fat individual, let alone a queer woman, that is not denigrating and oppressive in conventional media outlets and contemporary visual culture. But even as the negative imagery of fat individuals has expanded over the past forty years in mainstream distribution channels, fat-positive imagery has come to the fore within many feminist and lesbian publications during this same time frame. This article looks at the strategies of representation taken by three contemporary United States lesbian feminist periodicals in visualizing fat and lesbian women within their pages since the 1980s.

Enhanced diffusion with abnormal temperature dependence in underdamped space-periodic systems subject to time-periodic driving

NASA Astrophysics Data System (ADS)

Marchenko, I. G.; Marchenko, I. I.; Zhiglo, A. V.

2018-01-01

We present a study of the diffusion enhancement of underdamped Brownian particles in a one-dimensional symmetric space-periodic potential due to external symmetric time-periodic driving with zero mean. We show that the diffusivity can be enhanced by many orders of magnitude at an appropriate choice of the driving amplitude and frequency. The diffusivity demonstrates abnormal (decreasing) temperature dependence at the driving amplitudes exceeding a certain value. At any fixed driving frequency Ω normal temperature dependence of the diffusivity is restored at low enough temperatures, T periodic ("square") driving.

Serum Proteomic Changes after Randomized Prolonged Erythropoietin Treatment and/or Endurance Training: Detection of Novel Biomarkers

PubMed Central

Christensen, Britt; Ludvigsen, Maja; Nellemann, Birgitte; Kopchick, John J.; Honoré, Bent; Jørgensen, Jens Otto L.

2015-01-01

Introduction Despite implementation of the biological passport to detect erythropoietin abuse, a need for additional biomarkers remains. We used a proteomic approach to identify novel serum biomarkers of prolonged erythropoiesis-stimulating agent (ESA) exposure (Darbepoietin-α) and/or aerobic training. Trial Design Thirty-six healthy young males were randomly assigned to the following groups: Sedentary-placebo (n = 9), Sedentary-ESA (n = 9), Training-placebo (n = 10), or Training-ESA (n = 8). They were treated with placebo/Darbepoietin-α subcutaneously once/week for 10 weeks followed by a 3-week washout period. Training consisted of supervised biking 3/week for 13 weeks at the highest possible intensity. Serum was collected at baseline, week 3 (high dose Darbepoietin-α), week 10 (reduced dose Darbepoietin-α), and after a 3-week washout period. Methods Serum proteins were separated according to charge and molecular mass (2D-gel electrophoresis). The identity of proteins from spots exhibiting altered intensity was determined by mass spectrometry. Results Six protein spots changed in response to Darbepoietin-α treatment. Comparing all 4 experimental groups, two protein spots (serotransferrin and haptoglobin/haptoglobin related protein) showed a significant response to Darbepoietin-α treatment. The haptoglobin/haptoglobin related protein spot showed a significantly lower intensity in all subjects in the training-ESA group during the treatment period and increased during the washout period. Conclusion An isoform of haptoglobin/haptoglobin related protein could be a new anti-doping marker and merits further research. Trial Registration ClinicalTrials.gov NCT01320449 PMID:25679398

Angiotensin receptor antagonist vs. angiotensin-converting enzyme inhibitor in Asian subjects with type 2 diabetes and albuminuria - a randomized crossover study.

PubMed

Lim, S-C; Koh, A F Y; Goh, S K; Chua, C-L; Heng, B-L; Subramaniam, T; Sum, C-F

2007-07-01

Subjects with type 2 diabetes mellitus (T2DM) and albuminuria are at risk for progressive diabetic nephropathy. The relative blood pressure lowering and antialbuminuric efficacy of angiotensin receptor antagonist (ARB) vs. angiotensin-converting enzyme (ACE) inhibitor has not been well studied. Forty-one ARB- and ACE inhibitor-naive T2DM subjects with albuminuria (>30 mg/g creatinine) were given either 50 mg of losartan (ARB) or 20 mg of quinapril (ACE inhibitor) (50% maximum dose) for 4 weeks, with a 4-week wash-out period in-between interventions in a crossover fashion. The order of intervention was randomized. The primary endpoint was the reduction of blood pressure and albuminuria. Secondary endpoint was changes in plasma transforming growth factor beta (TGF-beta). Among the 41 subjects, 66% were male. The mean age (s.d.) was 52 (10) years, and duration of diabetes was 8 (14) years. Blood pressure reduction (though not statistically significant) was similar on both interventions [systolic: losartan 3 (15) vs. quinapril 2 (13) mmHg, p = 0.52; diastolic: losartan 1 (9) vs. quinapril 2 (8) mmHg, p = 0.55]. However, amelioration of albuminuria [mean (s.e.)] was significantly greater with losartan [losartan vs. quinapril: -93 (82) vs. -49 (65) mg/g, p = 0.02]. There was no change in plasma TGF-beta levels [mean (s.d.)] on either treatment, losartan [before 12.1 (8.9) vs. after 11.9 (9.6) ng/ml, p = 0.68] and quinapril [11.1 (7.9) vs. 11.1 (7.8) ng/ml, p = 0.87). In Asian subjects with T2DM and albuminuria, 4 weeks of losartan therapy at 50 mg daily appeared to have greater antialbuminuric effect than 20 mg of quinapril.

Short-Term Effect of Autogenic Drainage on Ventilation Inhomogeneity in Adult Subjects With Stable Non-Cystic Fibrosis Bronchiectasis.

PubMed

Poncin, William; Reychler, Grégory; Leeuwerck, Noémie; Bauwens, Nathalie; Aubriot, Anne-Sophie; Nader, Candice; Liistro, Giuseppe; Gohy, Sophie

2017-05-01

Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from a multiple-breath washout test, is a promising tool for assessing airway function in patients with non-cystic fibrosis bronchiectasis. However, it is unknown whether ventilation inhomogeneity could improve after successful elimination of excessive secretions within bronchiectasis. The objective of this work was to assess the short-term effects of lung secretion clearance using the autogenic drainage technique on standard lung function tests and LCI in subjects with non-cystic fibrosis bronchiectasis. Nitrogen-based multiple-breath washout, spirometry, and body plethysmography tests were performed 30 min before autogenic drainage in adults with stable non-cystic fibrosis bronchiectasis. The autogenic drainage session was followed by a 5-min break, after which the tests were repeated in the same order. Sputum expectorated during autogenic drainage was quantified as dry weight and correlated with change between post- and pre-measurements (Δ). Paired t test or Wilcoxon signed-rank tests were used to compare pre- and post-autogenic drainage measurement outcomes. A P value of ≤.05 was considered as statistically significant. Twenty-four subjects were studied (18 females, median age [range]: 65 [21-81] y). Mean ± SD LCI significantly improved after autogenic drainage (10.88 ± 2.62 vs 10.53 ± 2.35, P = .042). However, only 20% of subjects with mucus hyperproduction during autogenic drainage had a ΔLCI that exceeded measurement variability. The percent of predicted slow vital capacity (SVC%) also slightly improved (88.7 ± 19.3% vs 90 ± 19.1%, P = .02). ΔLCI was inversely related to dry sputum weight (r = -.48, P = .02) and ΔSVC% (r = -.64, P = .001). ΔSVC% also correlated with dry sputum weight (r = 0.46, P = .02). In adults with non-cystic fibrosis bronchiectasis and mucus hypersecretion, autogenic drainage improved ventilation inhomogeneity. LCI change may be the result of the

Enhanced Photoacoustic Gas Analyser Response Time and Impact on Accuracy at Fast Ventilation Rates during Multiple Breath Washout

PubMed Central

Horsley, Alex; Macleod, Kenneth; Gupta, Ruchi; Goddard, Nick; Bell, Nicholas

2014-01-01

Background The Innocor device contains a highly sensitive photoacoustic gas analyser that has been used to perform multiple breath washout (MBW) measurements using very low concentrations of the tracer gas SF6. Use in smaller subjects has been restricted by the requirement for a gas analyser response time of <100 ms, in order to ensure accurate estimation of lung volumes at rapid ventilation rates. Methods A series of previously reported and novel enhancements were made to the gas analyser to produce a clinically practical system with a reduced response time. An enhanced lung model system, capable of delivering highly accurate ventilation rates and volumes, was used to assess in vitro accuracy of functional residual capacity (FRC) volume calculation and the effects of flow and gas signal alignment on this. Results 10–90% rise time was reduced from 154 to 88 ms. In an adult/child lung model, accuracy of volume calculation was −0.9 to 2.9% for all measurements, including those with ventilation rate of 30/min and FRC of 0.5 L; for the un-enhanced system, accuracy deteriorated at higher ventilation rates and smaller FRC. In a separate smaller lung model (ventilation rate 60/min, FRC 250 ml, tidal volume 100 ml), mean accuracy of FRC measurement for the enhanced system was minus 0.95% (range −3.8 to 2.0%). Error sensitivity to flow and gas signal alignment was increased by ventilation rate, smaller FRC and slower analyser response time. Conclusion The Innocor analyser can be enhanced to reliably generate highly accurate FRC measurements down at volumes as low as those simulating infant lung settings. Signal alignment is a critical factor. With these enhancements, the Innocor analyser exceeds key technical component recommendations for MBW apparatus. PMID:24892522

Treatment response of airway clearance assessed by single-breath washout in children with cystic fibrosis.

PubMed

Abbas, Chiara; Singer, Florian; Yammine, Sophie; Casaulta, Carmen; Latzin, Philipp

2013-12-01

We studied the ability of 4 single-breath gas washout (SBW) tests to measure immediate effects of airway clearance in children with CF. 25 children aged 4-16 years with CF performed pulmonary function tests to assess short-term variability at baseline and response to routine airway clearance. Tidal helium and sulfur hexafluoride (double-tracer gas: DTG) SBW, tidal capnography, tidal and vital capacity nitrogen (N2) SBW and spirometry were applied. We analyzed the gasses' phase III slope (SnIII--normalized for tidal volume) and FEV1 from spirometry. SnIII from tidal DTG-SBW, SnIII from vital capacity N2-SBW, and FEV1 improved significantly after airway clearance. From these tests, individual change of SnIII from tidal DTG-SBW and FEV1 exceeded short-term variability in 10 and 6 children. With the tidal DTG-SBW, an easy and promising test for peripheral gas mixing efficiency, immediate pulmonary function response to airway clearance can be assessed in CF children. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Thrombotic Markers in Metabolic Syndrome Subjects Exposed to Diesel Exhaust

PubMed Central

Carlsten, C.; Kaufman, J. D.; Trenga, C. A.; Allen, J.; Peretz, A.; Sullivan, J. H.

2011-01-01

Traffic-derived particulate matter (PM) is associated with cardiovascular morbidity and mortality, but the mechanism of this association is unclear. Prothrombotic processes have been linked to PM in epidemiological and animal models, but have not been consistently implicated in controlled human models. Diesel exhaust (DE) is a major contributor to PM. We conducted a controlled human exposure of DE in subjects with metabolic syndrome. The study objective was to evaluate DE exposure effects on prothrombotic markers in a population vulnerable to cardiovascular disease. A randomized, crossover, double-blinded design was used: 16 subjects with metabolic syndrome exposed on 3 different days (≥2 wk washout) to DE at 0 (filtered air, FA), 100 μg PM2.5/m3 (DE100) and 200 μg PM2.5/m3 (DE200). We assessed DE-associated changes in D-dimer, von Willebrand factor (VWF), and plasmin activator inhibitor-1 (PAI-1) at 3, 7, and 22 h after exposure initiation. A DE200-attributable decrease (1.17-fold; CI 1.04 to 1.34) in VWF was noted at 7 h. Significant changes did not occur in other primary endpoints. As previously noted with healthy subjects, strong diurnal patterns in PAI-1 were observed. Thus, in a novel study, we were unable to demonstrate a prothrombotic effect of moderate-dose diesel exhaust exposure in a population at risk for cardiovascular disease. PMID:18668408

Axillary pH and influence of deodorants.

PubMed

Stenzaly-Achtert, S.; Schölermann, A.; Schreiber, J.; Diec, K. H.; Rippke, F.; Bielfeldt, S.

2000-05-01

BACKGROUND/AIMS: In moist intertriginous regions, such as the armpit, the pH value is physiologically higher than in other skin regions. The regulation of the axillary pH-value was examined in an open study with 48 subjects in three groups with n=16 each. METHODS: In the first 10 days (run-in) the subjects received a standard treatment in the axilla with shaving, cleansing and application of a pH-neutral deodorant. This was followed by a 5 day treatment period with the three test products (pH5 Eucerin(R) Deodorant Roll-on, Deodorant Balsam Spray, Deodorant Cream). The study was concluded by a wash-out period with procedures identical to the run-in phase. The pH was measured with a calibrated pH-meter. RESULTS: A significant pH reduction was shown during the treatment period when compared to the run-in phase. The Deodorant Roll-on induced a reduction of the mean pH values from 6.1 to 5.3, the Deodorant Balsam Spray from 6.5 to 5.7 and the Deodorant Cream from 6.2 to 5.3. During the wash-out period all pH values returned to baseline. CONCLUSION: All of the deodorants tested demonstrated a significant reduction in axillary pH. There is evidence that a high skin pH promotes the growth of several microorganisms that produce malodor. Therefore, the regulation of pH may contribute to the deodorant efficacy of the test products.

Subcutaneous blood flow in psoriasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klemp, P.

1985-03-01

The simultaneously recorded disappearance rates of /sup 133/xe from subcutaneous adipose tissue in the crus were studied in 10 patients with psoriasis vulgaris using atraumatic labeling of the tissue in lesional skin (LS) areas and symmetrical, nonlesional skin (NLS) areas. Control experiments were performed bilaterally in 10 younger, healthy subjects. The subcutaneous washout rate constant was significantly higher in LS, 0.79 +/- 0.05 min-1 x 10(2) compared to the washout rate constant of NLS, 0.56 +/- 0.07 min-1. 10(2), or the washout rate constant in the normal subjects, 0.46 +/- 0.17 min-1 x 10(2). The mean washout rate constant inmore » NLS was 25% higher than the mean washout rate constant in the normal subjects. The difference was, however, not statistically significant. Differences in the washout rate constants might be due to abnormal subcutaneous tissue-to-blood partition (lambda) in the LS--and therefore not reflecting the real differences in the subcutaneous blood flow (SBF). The lambda for /sup 133/Xe was therefore measured--using a double isotope washout method (/sup 133/Xe and (/sup 131/I)antipyrine)--in symmetrical sites of the lateral crus in LS and NLS of 10 patients with psoriasis vulgaris and in 10 legs of normal subjects. In LS the lambda was 4.52 +/- 1.67 ml/g, which was not statistically different from that of NLS, 5.25 +/- 2.19 ml/g, nor from that of normal subcutaneous tissue, 4.98 +/- 1.04 ml/g. Calculations of the SBF using the obtained lambda values gave a significantly higher SBF in LS, 3.57 +/- 0.23 ml/100 g/min, compared to SBF in the NLS, 2.94 +/- 0.37 ml/100 g/min. There was no statistically significant difference between SBF in NLS and SBF in the normal subjects. The increased SBF in LS of psoriatics might be a secondary phenomenon to an increased heat loss in the lesional skin.« less

Lansoprazole 15 mg once daily for 14 days is effective for treatment of frequent heartburn: results of 2 randomized, placebo-controlled, double-blind studies.

PubMed

Kushner, Pamela R; Snoddy, Andrew M; Gilderman, Larry; Peura, David A

2009-07-01

To investigate the efficacy and safety of a 14-day treatment period with lansoprazole 15 mg for frequent heartburn in patients who are likely to select a nonprescription medication before consulting a prescriber. Adults with untreated frequent heartburn > or = 2 days a week over the past month were recruited for 2 identical multicenter, double-blind studies conducted with a 1-week screening and heartburn medication washout, a 1-week placebo run-in, a 2-week placebo-controlled treatment, and a 1-week placebo follow-up. After the washout and placebo run-in, subjects were randomly assigned to receive lansoprazole 15 mg or placebo once daily for 14 days in a double-blind fashion. Antacid tablets were permitted as rescue medication. Endpoints included percentage of 24-hour days without heartburn (primary), percentage of night-times without heartburn, and percentage of subjects without heartburn during day 1 of treatment (secondary endpoints). Data were collected daily via an interactive voice response system. In studies 1 and 2, 282 and 288 subjects, respectively, were randomly assigned to lansoprazole, and 282 in each study received placebo. The mean percentage of days without heartburn was greater among lansoprazole recipients compared with placebo recipients (P < 0.0001). Significantly more subjects treated with lansoprazole also reported no night-time heartburn and no heartburn during day 1 of the 14-day treatment. Adverse events were infrequent and were similar for lansoprazole and placebo groups. During the 14-day treatment period in a population with frequent heartburn who were likely to select a medication without consulting a prescriber, lansoprazole 15 mg once daily showed rapid and sustained effectiveness throughout a 24-hour period and was well tolerated.

EFFECTS OF LASER RADIATION ON MATTER: Growth of periodic structures on the surface of germanium subjected to pulsed laser radiation

NASA Astrophysics Data System (ADS)

Barsukov, D. O.; Gusakov, G. M.; Frolov, A. I.

1991-12-01

An experimental investigation was made of the dynamics of growth of periodic surface structures due to the interaction with pulsed laser radiation. Samples of Ge were subjected to laser pulses (λ = 1.06 μm, τ = 70 ns) with energy densities in the range 0.5-5.5 J/cm2. An investigation was made of the dynamics of the first-order diffraction of probe (λ = 0.53 μm) laser pulses with a time resolution 4 ns when p- and s-polarized laser radiation was incident at angles close to normal. A strong nonlinearity of the growth of such periodic surface structures was observed. The energy density from which such growth began depended on the quality of the polished Ge surface. The parameters of the dynamics of the growth of these structures were estimated.

Book Reviews in Periodicals.

ERIC Educational Resources Information Center

Ettelt, Harold J.

All recent issues of periodicals found which contain indexed book reviews are listed in this compilation from Drake Memorial Library at the New York State University at Brockport. The periodicals are listed by 29 subject headings in this informal guide designed to be used at Drake Library. The number of reviews in the periodical in a recent year…

Pharmacokinetic comparison of a fixed-dose combination versus concomitant administration of fimasartan, amlodipine, and rosuvastatin using partial replicated design in healthy adult subjects.

PubMed

Oh, Minkyung; Ghim, Jong-Lyul; Park, Sung-Eun; Kim, Eun-Young; Shin, Jae-Gook

2018-01-01

The aim of this study was to compare the pharmacokinetics (PK) and safety profiles of a fixed-dose combination (FDC) formulation of fimasartan, amlodipine, and rosuvastatin with the co-administration of the two products by using a replicated crossover study design in healthy male subjects. This was an open-label, randomized, three-sequence, three-period replicated crossover study in healthy male subjects. The replicated crossover design was done because of high coefficient of variation of PK parameter for fimasartan, that is, >30%. With a 14 days washout period, an FDC tablet containing 60 mg fimasartan, 10 mg amlodipine, and 20 mg rosuvastatin was administered only once, and separate formulations of fimasartan/amlodipine 60 mg/10 mg FDC tablet and 20 mg rosuvastatin tablet administered twice. Blood samples were collected up to 72 hours following drug administration. The plasma concentrations of fimasartan, amlodipine, and rosuvastatin were measured by liquid chromatography tandem mass spectrometry. Safety was assessed by evaluating vital signs, clinical laboratory parameters, physical examinations, and medical interviews. The geometric mean ratios and 90% confidence intervals (CIs) for the maximum plasma concentration (C max ) and area under the curve from time zero to the last measurable sampling time (AUC t ) were 1.0776 (0.9201-1.2622) and 0.9978 (0.9538-1.0439) for fimasartan, 1.0038 (0.9782-1.0301) and 1.0055 (0.9828-1.0288) for amlodipine, and 1.0006 (0.9290-1.0776) and 0.9986 (0.9532-1.0461) for rosuvastatin, respectively. A total of 22 adverse events (AEs) were reported by 60 subjects; there were no significant differences in the incidence of AEs between the two groups. The 90% CI of the C max of fimasartan was within the widened acceptance limit, ln(0.6984)-ln(1.4319). The 90% CIs of the other PK parameters for drugs were between ln(0.8) and ln(1.25). These results suggest that the FDC formulation is pharmacokinetically bioequivalent and has a similar

A comparison of lumbopelvic motion patterns and erector spinae behavior between asymptomatic subjects and patients with recurrent low back pain during pain-free periods.

PubMed

Sánchez-Zuriaga, Daniel; López-Pascual, Juan; Garrido-Jaén, David; García-Mas, Maria Amparo

2015-02-01

The purpose of this study was to determine the patterns of lumbopelvic motion and erector spinae (ES) activity during trunk flexion-extension movements and to compare these patterns between patients with recurrent low back pain (LBP) in their pain-free periods and matched asymptomatic subjects. Thirty subjects participated (15 patients with disc herniation and recurrent LBP in their pain-free periods and 15 asymptomatic control subjects). A 3-dimensional videophotogrammetric system and surface electromyography (EMG) were used to record the angular displacements of the lumbar spine and hip in the sagittal plane and the EMG activity of the ES during standardized trunk flexion-extension cycles. Variables were maximum ranges of spine and hip flexion; percentages of maximum lumbar and hip flexion at the start and end of ES relaxation; average percentages of EMG activity during flexion, relaxation, and extension; and flexion-extension ratio of myoelectrical activity. Recurrent LBP patients during their pain-free period showed significantly greater ES activation both in flexion and extension, with a higher flexion-extension ratio than controls. Maximum ranges of lumbar and hip flexion showed no differences between controls and patients, although patients spent less time with their lumbar spine maximally flexed. This study showed that reduced maximum ranges of motion and absence of ES flexion-relaxation phenomenon were not useful to identify LBP patients in the absence of acute pain. However, these patients showed subtle alterations of their lumbopelvic motion and ES activity patterns, which may have important clinical implications. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Effect of pinching-evoked pain on jaw-stretch reflexes and exteroceptive suppression periods in healthy subjects.

PubMed

Biasiotta, A; Peddireddy, A; Wang, K; Romaniello, A; Frati, A; Svensson, P; Arendt-Nielsen, L

2007-10-01

To investigate the influence of conditioning cutaneous nociceptive inputs by a new "pinch" model on the jaw-stretch reflex and the exteroceptive suppression periods (ES1 and ES2) in jaw muscles. The jaw-stretch reflex was evoked with the use of a custom-made muscle stretcher and electrical stimuli were used to evoke an early and late exteroceptive suppression period (ES1 and ES2) in the jaw-closing muscles. Electromyographic (EMG) activity was recorded bilaterally from the masseter and temporalis muscles. These brainstem reflexes were recorded in 19 healthy men (28.8+/-1.1 years) during three different conditions: one painful clip applied to the earlobe; one painful clip applied to the nostril, and four painful clips applied simultaneously to the earlobe, nostril, eyebrow, and lower lip. Pain intensity induced by the application of the clips was scored continuously by the subjects on a 100mm visual analogue scale (VAS). The highest VAS pain scores were evoked by placement of four clips (79+/-0.5mm). There was no significant modulation of the jaw-stretch reflex (ANOVAs: P=0.929), the ES1 (P=0.298) or ES2 (P=0.082) in any of the three painful conditions. Intense and tonic cutaneous pain could be elicited by this new "pinch" pain model; however, there was no significant modulation on either excitatory or inhibitory brainstem reflex responses. The novel observation that high-intensity pinch stimuli applied to the craniofacial region fail to modulate two different brainstem reflexes is in contrast to other experimental pain studies documented facilitation of the jaw-stretch reflexes or inhibition of exteroceptive suppression periods. The clinical implication of the present findings is that only some craniofacial pain conditions could be expected to show perturbation of the brainstem reflex responses.

5 CFR 9901.512 - Probationary periods.

Code of Federal Regulations, 2010 CFR

2010-01-01

... period in the new position; i.e., the supervisory probationary period does not start over. (1) Crediting... probationary period is subject to the probationary period prescribed for the new position. Service in the former position is credited toward completion of the probationary period in the new position. (ii...

[Periodic oscillating respiration outside of comatous stages].

PubMed

Jammes, Y; Delpierre, S; Zwirn, P; Nicoli, M M

1977-04-01

A periodic oscillating breathing was observed in 11 subjects during study of their pulmonary function. All these patients were male and more than 50 years old. A cardiovascular disease was clinically evident in eight of them. Arterial hypoxemia was found in five subjects and a light hypocapnia in three. Analysis of oscillating rhythms first, revealed unexistence of ventilatory pauses between periods of deep breaths in some subjects and secondly, showed existence of permanent or discontinuous periodic rhythms. Breath by breath changes in ventilation were essentially induced by oscillations in tidal volume. Discontinuous oscillating breathing appeared after forced maximal inspiration and this periodic rhythm was frequently associated with sights. This periodic breathing began or persisted under progressive hypoxia but disappeared under normobaric hyperoxia. These data are discussed in terms of changes in the ventilatory control system and in central regulation of breathing patterns.

Absolute Bioavailability and Effect of Food on the Disposition of Safinamide Immediate Release Tablets in Healthy Adult Subjects.

PubMed

Seithel-Keuth, Annick; Johne, Andreas; Freisleben, Achim; Kupas, Katrin; Lissy, Michael; Krösser, Sonja

2013-01-01

The objectives of this study were to establish the basic intravenous (IV) single-dose PK of safinamide and its major human metabolites, the absolute bioavailability (BA) and food effect on safinamide tablets. Fourteen healthy adult male and female subjects received 50 mg safinamide single-dose treatments according to a randomized, 3-period, 2-sequence crossover design: immediate release (IR) tablets, administered after an overnight fast and after a standardized high-fat, high-calorie breakfast, and IV solution, administered over 30 minutes. Treatments were separated by wash-out intervals of at least 17 days. Serial blood samples were collected for 240 hours postdosing to evaluate safinamide parent drug and metabolite concentrations for the determination of PK parameters. The absolute BA of safinamide 50 mg IR tablets was high, with geoMean AUC0-∞ ratios of about 95% (90% CI: 90-99%) indicating that safinamide is virtually completely absorbed after oral administration. Safinamide IR tablets did not display a food effect on exposure parameters; both 90% CIs for the ratios fed/fasted of AUC0-∞ and Cmax were entirely within the bioequivalence acceptance margins of 80-125%. Only tmax was delayed by about 30% in the fed state. Oral and IV safinamide 50 mg single-dose administrations were generally well tolerated. © The Author(s) 2013.

A randomized, double-blind, placebo-controlled study of the effect of ezetimibe on glucose metabolism in subjects with type 2 diabetes mellitus and hypercholesterolemia.

PubMed

Saito, Itori; Azuma, Kyoichi; Kakikawa, Taro; Oshima, Nobuyuki; Hanson, Mary E; Tershakovec, Andrew M

2015-05-01

Recent evidence points to an increased incidence of new-onset diabetes and a negative impact on glucose parameters with statin use. This study examined the safety of ezetimibe vs placebo for change from baseline to week 24 in HbA1c (primary endpoint), glycoalbumin, and fasting plasma glucose (secondary endpoints) in Japanese subjects with type 2 diabetes and hypercholesterolemia. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-site trial. Adults with type 2 diabetes and hypercholesterolemia whose LDL-C measured <140 mg/dl (subjects receiving lipid-lowering drugs) or <160 mg/dl (subjects not receiving lipid-lowering drugs) at the start of the screening phase, were randomized after a 5-week wash-out period to ezetimibe 10 mg or placebo (1:1) for 24 weeks. Changes in HbA1c, glycoalbumin and fasting plasma glucose from baseline to week 24 were evaluated. The non-inferiority margin was set at 0.5% for HbA1c. Overall, 152 subjects were randomized (75 to ezetimibe and 77 to placebo). From baseline to 24 weeks, HbA1c significantly increased in both the ezetimibe and placebo groups (between-treatment difference 0.08 [95% CI: -0.07 to 0.23]). Ezetimibe was statistically non-inferior to placebo. At 24 weeks, the mean change from baseline in glycoalbumin levels (between-treatment differences 0.00 [95% CI: -0.47, 0.47]) and fasting plasma glucose (between-treatment differences -4.8 [95% CI: -12.1, 2.1]) were similar in both treatment groups. These results suggest that ezetimibe 10 mg does not result in dysregulation of glucose metabolism in Japanese patients with type 2 diabetes and hypercholesterolemia over 24 weeks of treatment. ClinicalTrials.gov identifier NCT01611883 .

Peritoneal clearances in hypertensive CAPD patients after oral administration of clonidine, enalapril, and nifedipine.

PubMed

Favazza, A; Motanaro, D; Messa, P; Antonucci, F; Gropuzzo, M; Mioni, G

1992-01-01

The authors investigated whether the reduction of arterial pressure, induced by the oral administration of clonidine (CLO), enalapril (EN), and nifedipine (NIF), has any effect on peritoneal transport rates. The study was performed in nine hypertensive patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The patients were submitted to administration of CLO, EN, and NIF, each in randomized succession for two weeks, after withdrawal of any hypotensive therapy for eight days (washout period). The nine patients underwent a four-hour dwell exchange using a 2.27 g/dL glucose two-liter bag after washout and after each hypotensive period. The following parameters were analyzed: mean arterial pressure (MAP), performed in the sitting position; net ultrafiltration; effluent/initial dialysate glucose ratio (GL D/Do); peritoneal clearance of K, BUN, creatinine (Cr), phosphate, beta-2 microglobulin (beta 2), total proteins, and the ratio between beta 2 and Cr clearance. Moreover, residual renal Cr and beta 2 clearances were analyzed. The three drugs significantly reduced MAP at a similar rate. The peritoneal transport parameters after CLO were similar to the results in the washout period. On the contrary, after EN and NIF therapy, Cr and beta 2 clearances were significantly increased, and GL D/Do decreased in comparison to the washout period. The other peritoneal transport parameters after EN and NIF were similar to the washout period. Residual renal Cr and beta 2 clearances after the three drugs were similar to those in the washout. these data suggest that after two weeks of therapy with EN and NIF, glucose, Cr, and beta 2 peritoneal transports are influenced by these hypotensive drugs irrespective of the effect on the arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Mother chair reparation to decrease subjective disorders in exclusive breast-feeding period

NASA Astrophysics Data System (ADS)

Santiana, M. A.; Yusuf, M.; Lokantara, W. D.

2018-01-01

Exclusive breastfeeding is the responsibility of the mother after childbirth. A specific constraint arise for the mother when during the breastfeeding process, the place is not in accordance with the physiological condition of the mother's body. A not physiologically corrected lactation place will cause subjective disorders for breastfeeding mothers. Complaints that arise include quick tiredness, with certain muscles sore and pain, which will ultimately decrease the motivation of the mothers to perform exclusive breastfeeding especially in the first six months of the baby's birth. An improved ergonomic designed chair, this research used experimental method with group within treatment (treatment by subject) to solve the problem. The study took place in Maternity Clinic “CB” Badung regency, Bali. Subjective disorders are measured based on general fatigue and musculoskeletal disorders mothers breastfeeding. Fatigue is predicted using 30 items of questionnaires while musculoskeletal compaints are predicted from the Nordic Body Map questionnaire. Data were analyzed descriptively and inferentially in an experiment condition using using t-pair test. The results showed that there were significant differences in fatigue in general and skeletal musculoskeletal disorders between treatment 1 (using old chair) with treatment 2 (using repaired seats) in breastfeeding mothers. Fatigue in general decreased by 35.6% and skeletal musculoskeletal disorders decreased by 26.8%. It was concluded that improved breastfeeding mothers' seats may decrease subjective disorders during exclusive breastfeeding. It is therefore advisable for breastfeeding mothers to use seats that match their anthropometry.

Strawberries Added to the Usual Diet Suppress Fasting Plasma Paraoxonase Activity and Have a Weak Transient Decreasing Effect on Cholesterol Levels in Healthy Nonobese Subjects.

PubMed

Zasowska-Nowak, Anna; Nowak, Piotr J; Bialasiewicz, Piotr; Prymont-Przyminska, Anna; Zwolinska, Anna; Sarniak, Agata; Wlodarczyk, Anna; Markowski, Jaroslaw; Rutkowski, Krzysztof P; Nowak, Dariusz

2016-07-01

Strawberries can improve oxidants-antioxidants balance and reduce some cardiovascular risk factors in obese subjects. Paraoxonase-1 (PON-1) is a high-density lipoprotein-associated enzyme with antioxidant properties that can protect from coronary artery disease in humans. We examined the effect of strawberry consumption on plasma PON-1 activity and lipid profile in healthy nonobese subjects. Thirty-one subjects (body mass index [BMI] 24.4 ± 4.0 kg/m(2)) on their usual diet consumed 500 g of strawberry pulp daily for 30 days (first course) and after a 10-day washout the cycle was repeated (second course). Fasting blood and spot morning urine samples were collected before, during, and after each strawberry course (8 time points) for determination of paraoxonase and arylesterase PON-1 activities and lipid profile. Twenty subjects served as controls with respect to cholesterol and PON-1 activities changes over the study period. Strawberries decreased mean plasma paraoxonase PON-1 activity and this effect was more evident after the second course (by 11.6%, p < 0.05) than after the first course (5.4%, p = 0.06), whereas arylesterase activity was constant. Strawberries altered total cholesterol levels (p < 0.05) with a tendency to transiently decrease it (by 5.1%) only after 15 days of the first course. Triglycerides and high- and low-density lipoprotein cholesterol did not change in response to fruit consumption. No changes in PON-1 activities and lipid profile were noted in controls. Paraoxonase correlated with arylesterase activity (ƿ from 0.33 to 0.46 at the first 7 time points, p < 0.05). This association disappeared at the end of study (ƿ = 0.07) when the strongest inhibition of paraoxonase was noted. Supplementation of the usual diet with strawberries decreased paraoxonase PON-1 activity and did not improve lipid profiles in healthy nonobese subjects. Further studies are necessary to establish the clinical significance of paraoxonase suppression and to

Correlation Between High-sensitivity C-reactive Protein and Reactive Oxygen Metabolites During A One-year Period Among Asymptomatic Subjects

PubMed Central

Kotani, Kazuhiko; Taniguchi, Nobuyuki

2012-01-01

Background Inflammation and oxidative stress are associated with human health and the disease status. The present study aimed to investigate the longitudinal correlation between the diacron reactive oxygen metabolites (d-ROMs) level, as an oxidative stress-related marker, and high-sensitivity C-reactive protein (hsCRP), as an inflammatory marker, during a one-year period among asymptomatic subjects. Methods The data, including anthropometric and biochemical markers, were collected at baseline and after the one-year period from 71 participants (male/female = 41/30, mean age 50 years). The correlation between the changes of the d-ROMs and hsCRP levels during the study period was examined. Results A simple correlation analysis showed a significant and positive correlation to exist between the changes of the d-ROMs and hsCRP levels (r = 0.40, P < 0.01). This significant correlation remained independent in a multiple linear regression analysis adjusted for confounding factors. Conclusions The present findings suggest that the relationship between the d-ROMs and hsCRP levels could be prospectively followed, and that monitoring both markers may help to better understand the cooperation of inflammation and oxidative stress in association with health and disease. Further studies are necessary to clarify the biological mechanism(s) responsible for the observed relationship. Keywords Oxidative stress; Oxygen reactive species; Inflammation; CRP PMID:22383928

26 CFR 301.7609-5 - Suspension of periods of limitations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... accountant for B, requiring production of records relating to B's income tax liabilities for 2003. The... prosecutions) for the tax period or periods that are the subject of the summons are suspended for the period... 6501 and 6531 for the tax period or periods that are the subject of the summons are suspended for the...

Systematic Review of Bilateral Independent Periodic Discharges Written for Topical Journal Subject on Periodic Discharges.

PubMed

Freund, Brin; Kaplan, Peter W

2018-05-01

Periodic discharges (PDs) are EEG patterns that may have important clinical and prognostic implications. There are different subtypes of PDs that are delineated by their location, and each type may have different meaning regarding prognosis and clinical associations. Bilateral independent PDs are a subtype that have not been analyzed recently and remain poorly understood. In this article, we systematically review the literature to better describe bilateral independent PDs regarding underlying neuropathology, neuroimaging, and neuroexamination correlates, seizure incidence, EEG characteristics, their comparison with other PD subtypes, and prognostic meaning.

Relationship between the acid-inhibitory effects of two proton pump inhibitors and CYP2C19 genotype in Japanese subjects: a randomized two-way crossover study.

PubMed

Furuta, K; Adachi, K; Ohara, S; Morita, T; Tanimura, T; Koshino, K; Kinoshita, Y

2010-01-01

This two-way crossover study investigated possible differences between the proton pump inhibitors, omeprazole and rabeprazole, in their effect on gastric acid secretion in Japanese subjects with differing cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotypes. A total of 23 Helicobacter pylori-negative healthy volunteers received omeprazole 20 mg/day and rabeprazole 10 mg/day. Each drug treatment was given for a continuous 7-day period allocated in random order, with an interval of at least 1 week between drug treatment periods to allow for wash-out. Intragastric pH was measured on days 1 and 7. Overall median intragastric pH levels at 7 and 8 h after the first administration were significantly higher with omeprazole. There was no significant difference in intragastric pH in homozygous extensive metabolizers, whereas intragastric pH was significantly higher with omeprazole in combined data from heterozygous extensive metabolizers and poor metabolizers at 6, 7 and 8 h after the first drug administration. There were no significant differences in intragastric pH between omeprazole and rabeprazole irrespective of genotype on day 7 of administration. In conclusion, on day 1 the time to onset of the antisecretory action of 20 mg/day omeprazole was more rapid than that of 10 mg/day rabeprazole in Japanese individuals who have a higher incidence of the CYP2C19 poor metabolizer genotype, however by day 7 no difference in antisecretory effect was found, regardless of genotype.

Repeated exposures to diisopropylfluorophosphate result in impairments of sustained attention and persistent alterations of inhibitory response control in rats

PubMed Central

Terry, Alvin V.; Callahan, Patrick M.; Beck, Wayne D.; Vandenhuerk, Leah; Sinha, Samantha; Bouchard, Kristy; Schade, Rose; Waller, Jennifer L.

2014-01-01

Organophosphate (OP)-based chemicals are used worldwide for many purposes and they have likely saved millions of people from starvation and disease. However, due to their toxicity they can also pose a significant environmental risk. While considerable research has focused on the acute symptoms and long-term consequences of overtly toxic exposures to OPs, less attention has been given to the subject of repeated exposures to levels that are not associated with acute symptoms (subthreshold exposures). There is clinical evidence indicating that this type of OP exposure can lead to prolonged deficits in cognition; however only a few studies have addressed this issue prospectively in animal models. In this study, repeated subthreshold exposures to the OP nerve agent diisopropylfluorophosphate (DFP) were evaluated in a 5-Choice Serial Reaction Time Task (5C-SRTT), an animal model of sustained attention. Adult rats were trained to stably perform the 5C-SRTT and then injected subcutaneously with vehicle or DFP 0.5 mg/kg every other day for 30 days. Behavioral testing occurred daily during the DFP-exposure period and throughout a 45 day (OP-free) washout period. Compared to vehicle-treated controls, DFP-treated rats exhibited deficits in accuracy, increases in omissions and timeout responses during the OP exposure period, while no significant effects on premature responses, perseverative responses, or response latencies were noted. While the increase in timeout responses remained detectible during washout, all other DFP-related alterations in 5C-SRTT performance abated. When the demands of the task were increased by the presentation of variable intertrial intervals, premature responses were also elevated in DFP-treated rats during the washout period. These results indicate that repeated exposures to subthreshold doses of DFP lead to reversible impairments in sustained attention as well as persistent impairments of inhibitory response control in rats. PMID:24819591

Bright light therapy and melatonin in motor restless behaviour in dementia: a placebo-controlled study.

PubMed

Haffmans, P M; Sival, R C; Lucius, S A; Cats, Q; van Gelder, L

2001-01-01

The purpose of this study was to evaluate the effects of bright light therapy combined with melatonin on motor restless behaviour in dementia. Double-blind, placebo-controlled, cross-over trial consisting of four periods. One week wash-out was followed by a 2-week period of light therapy in combination with placebo or melatonin. The second wash-out period of 1 week was followed by 2 weeks of treatment (cross-over). Twenty-four bed medium-stay psychogeriatric ward at a Dutch psychiatric teaching hospital. Ten patients, who met the criteria for dementia (DSM-IV) and motor restless behaviour (subscale 10 of the GIP), were included. Informed consent was obtained by proxy. All subjects were exposed during 2x5 consecutive days for 30 minutes to 10,000 lux bright light and randomly administered 2.5 mg melatonin or placebo at 22.00 h. Clinical Global Impression (CGI), Dutch version of the geriatric behavioural observation scale (GIP), Social Dysfunction and Aggression Scale (SDAS) were assessed after each wash-out and treatment period. Outcome criteria were CGI, assessing motor restless behaviour, the SDAS, measuring extrovert aggression and the GIP, assessing social, psychomotor and emotional behaviour. Six demented inpatients completed the trial. Positive effects were found for the treatment combined with placebo. Patients were less restless and more co-operative. The condition with melatonin showed no additional positive effects, additionally, patients became more aggressive and showed the same or more disturbed behaviour. Bright light therapy has a positive effect on motor restless behaviour. Light therapy in combination with melatonin has no positive effects. The results might be explained by a possible overshoot of chronobiological synchronisation or the timing of the melatonin intake. Copyright 2001 John Wiley & Sons, Ltd.

Pharmacokinetic Profiles of Ticagrelor Orodispersible Tablets in Healthy Western and Japanese Subjects.

PubMed

Teng, Renli; Hammarberg, Maria; Carlson, Glenn F; Bokelund-Singh, Sara; Ruderfelt, Terese; Blychert, Eva

2017-11-01

Ticagrelor is an antiplatelet agent for patients with acute coronary syndrome or a history of myocardial infarction. Two studies compared pharmacokinetic profiles of orodispersible (OD) ticagrelor tablets versus immediate-release (IR) tablets in Western and Japanese subjects. Both studies were open-label, randomized, crossover, single-center trials. Thirty-six healthy subjects (94% white, 6% other race; Western study NCT02400333) and 42 Japanese healthy subjects (Japanese study NCT02436577) received a single 90-mg ticagrelor dose as an OD tablet [with/without water, and via a nasogastric tube (Western study only)], and an IR tablet; washout between treatments was ≥7 days. Assessments included ticagrelor and AR-C124910XX (active metabolite) plasma concentrations for pharmacokinetic analyses, and safety evaluations. In the Western study, the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for ticagrelor and AR-C124910XX maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC) were within the acceptance interval (80%-125%) for OD tablets (with/without water, via a nasogastric tube) versus the IR tablet; except for an ~15% lowering of ticagrelor C max (90% CI: 76.77%-93.78%) for the OD tablet taken with water. In the Japanese study, 90% CIs of the GMRs for AUC and C max of both ticagrelor and AR-C124910XX were all within the acceptance intervals for the OD (with/without water) versus IR tablet. No new safety issues were identified. Ticagrelor administered as an OD tablet to Western (without water, and via a nasogastric tube) and Japanese (with/without water) subjects was bioequivalent to the IR tablet.

Pharmacokinetics and Pharmacodynamics of Twice Daily and Once Daily Regimens of Empagliflozin in Healthy Subjects.

PubMed

Macha, Sreeraj; Brand, Tobias; Meinicke, Thomas; Link, Jasmin; Broedl, Uli C

2015-08-01

This study was undertaken to compare the steady-state pharmacokinetic and pharmacodynamic properties of empagliflozin 5 mg twice daily (BID) and 10 mg once daily (QD) in healthy subjects. In an open-label, 2-way crossover study, subjects (n = 16) received empagliflozin 5 mg BID for 5 days and empagliflozin 10 mg QD for 5 days in a randomized order, with a washout period of ≥6 days between each treatment. The primary objective was the comparison of the overall exposure during a 24-hour period at steady state (AUC0-24,ss) for empagliflozin, based on standard bioequivalence criteria, with BID and QD dose regimens. The study population comprised 7 (43.8%) men and 9 (56.3%) women with a baseline median age of 38.0 years (range, 23-47 years) and a median body mass index of 23.3 kg/m(2) (range, 19.8-27.8 kg/m(2)). Based on standard bioequivalence criteria, there was no difference in the overall exposure of empagliflozin between BID and QD dose regimens (geometric mean ratio of AUC0-24,ss for empagliflozin 5 mg BID compared with empagliflozin 10 mg QD = 99.36%; 90% CI, 94.29-104.71). For empagliflozin 10 mg QD, mean (%CV) AUC during the dosing interval was 1900 nmol · h/L (20.6%), mean (%CV) Cmax,ss was 330 nmol/L (25.3%), and median (range) Tmax,ss was 1.0 hour (0.7-2.0 hours). For empagliflozin 5 mg BID, mean (%CV) AUC during the dosing interval was 1010 nmol · h/L (15.1%) and 867 nmol · h/L (18.6%) after the morning and evening dose, respectively, mean (%CV) Cmax,ss was 193 nmol/L (16.5%) and 120 nmol/L (21.0%), respectively, and median Tmax,ss was 1.0 hour (range, 0.7-2.0 hours) and 2.0 hours (range, 1.0-4.0 hours), respectively. The mean (%CV) cumulative amount of glucose excreted in urine during 24 hours was 52.1 g (32.1%) with empagliflozin 5 mg BID and 43.9 g (30.3%) with empagliflozin 10 mg QD. Adverse events were reported in six subjects (37.5%) receiving empagliflozin 5 mg BID and four (25.0%) receiving empagliflozin 10 mg QD. Headache was the most frequent

Washout of heme-containing proteins dramatically improves tetrazolium-based infarct staining.

PubMed

Pitts, Kelly R; Stiko, Ann; Buetow, Bernard; Lott, Fred; Guo, Ping; Virca, Duke; Toombs, Christopher F

2007-01-01

Methods to determine infarct size following ischemia-reperfusion injury include gross staining with triphenyltetrazolium chloride (TTC) and perfusion of colored dyes to demarcate the non-ischemic zone. Infarcted tissue (INF) can typically appear a mottled tan to brownish color, making a border between INF and TTC-positive tissue difficult to discern. Previous work in our lab indicated that following TTC staining, prolonged washing of thick sections dramatically sharpened this boundary. Adult rats underwent 30 min ischemia via LAD ligation and reperfusion/recovery over 24 h. Hearts were then harvested, thick-sectioned, and stained with TTC. Stained sections were stored in PBS at 4 degrees C for up to 3 weeks. Histology on thin sections from infarcted hearts fixed directly after harvest revealed extensive hemorrhage within the INF. However, this hemorrhage is washed out when hearts are stored in PBS for 3 weeks. SDS-PAGE of PBS samples taken at 1, 2, and 3 weeks showed a low molecular weight band appearing over time. Peptide sequencing revealed the presence of several proteins including the heme-containing proteins (HCPs) hemoglobin, cytochrome c, and myoglobin. The loss of HCPs from thick sections to PBS corresponded with the blanching of the previously mottled INF within each section. HPLC analysis of these samples confirmed the loss of HCPs contributes to INF whitening. Further, analysis of infarct size values derived from heart slices with or without HCPs showed a significant decrease in measurement error when values were derived from slices without HCPs. These data suggest that HCPs in the heart tissue contribute to the non-uniform and discolored appearance of the INF, and that washout of these proteins produces an INF more easily distinguished from neighboring non-infarcted tissue. This method greatly reduces the error associated with infarct measurements and improves the analysis of the effects of drug treatments and other interventions designed to impact

40 CFR 35.9035 - Budget period.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Budget period. 35.9035 Section 35.9035... ASSISTANCE Financial Assistance for the National Estuary Program § 35.9035 Budget period. An applicant may choose its budget period in consultation with and subject to the approval of the Regional Administrator. ...

Nasal versus face mask for multiple-breath washout technique in preterm infants.

PubMed

Schulzke, S M; Deeptha, K; Sinhal, S; Baldwin, D N; Pillow, J J

2008-09-01

The large dead space associated with face masks might impede the accuracy and feasibility of multiple-breath washout (MBW) measurements in small infants. We asked if a low dead space nasal mask would provide measurements of resting lung volume and ventilation inhomogeneity comparable to those obtained with a face mask, when using the MBW technique. Unsedated preterm infants breathing without mechanical assistance and weighing between 1.50 and 2.49 kg were studied. Paired MBW tests with nasal and face masks were obtained using sulphur hexafluoride (SF(6)) as the tracer gas. The order of mask application was quasi-randomized. Bland-Altman method and intraclass correlation coefficient were used to analyze outcomes. Measurements were obtained in 20 infants with a mean (SD) postmenstrual age of 36 (1.4) w and a test weight of 2.0 (0.3) kg. The mean difference (95% CI) for nasal vs. face mask was -3.2 breaths/min (-6.2, -0.1 breaths/min) for respiratory rate, -1.0 ml/kg (-2.3, 0.3 ml/kg) for lung volume, 0.6 (0.1, 1.1) for lung clearance index, 0.2 (0.1, 0.3) for first to zeroeth moment ratio and 1.33 (0.6, 2.4) for second to zeroeth moment ratio. Paired measurements of lung volume showed acceptable agreement and good correlation, but there was poor agreement and poor correlation between indices of ventilation inhomogeneity obtained with the two masks. Functional dead space of the nasal mask was similar to that of the face mask despite its smaller water displacement volume. During MBW in infants below 2.5 kg body weight, a nasal mask results in comparable lung volume measurements. Indices of ventilation inhomogeneity may not be directly comparable using masks with different dead space. (c) 2008 Wiley-Liss, Inc.

Bioequivalence of generic lamotrigine 100-mg tablets in healthy Thai male volunteers: a randomized, single-dose, two-period, two-sequence crossover study.

PubMed

Srichaiya, Arunee; Longchoopol, Chaowanee; Oo-Puthinan, Sarawut; Sayasathid, Jarun; Sripalakit, Pattana; Viyoch, Jarupa

2008-10-01

Lamotrigine is an antiepileptic drug which has been used in the treatment of epilepsy and bipolar disorder. A search of the literature did not find previously published bioequivalence and pharmacokinetic evaluations of lamotrigine in healthy Thai male volunteers. The aim of this study was to compare the pharmacokinetic parameters between 2 brands of lamotrigine in healthy Thai male volunteers. A randomized, single-dose, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in healthy Thai males. Subjects were randomized to receive either the test or reference formulation in the first period. All subjects were required to be nonsmokers and without a history of alcohol or drug abuse. Plasma samples were collected over a 120-hour period after 100-mg lamotrigine administration in each period. A validated high-performance liquid chromatography ultraviolet method was used to analyze lamotrigine concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products, as defined by the US Food and Drug Administration (FDA), is determined when the ratio for the 90% CIs of the difference in the means of the log-transformed AUC(0-t), AUC(0-infinity), and C(max) of the 2 products are within 0.80 and 1.25. Adverse events were determined by measuring vital signs after dosing. Subjects were also asked if they suffered from undesirable effects such as nausea, vomiting, dizziness, and headache. This bioequivalence study was performed in 24 healthy Thai males (mean [SD] age, 20.5 [1.3] years; range, 19-24 years; weight, 62.5 [7.4] kg; height, 172.8 [6.9] cm; body mass index, 20.9 [2.0] kg/m(2)). The mean (SD) C(max) and T(max) of the test formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.2 (0.9) hours, respectively. The mean (SD) C(max) and T(max) of the reference formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.4 (1.0) hours, respectively. The mean

Association of Poor Subjective Sleep Quality With Risk for Death by Suicide During a 10-Year Period

PubMed Central

Bernert, Rebecca A.; Turvey, Carolyn L.; Conwell, Yeates; Joiner, Thomas E.

2014-01-01

IMPORTANCE Older adults have high rates of sleep disturbance, die by suicide at disproportionately higher rates compared with other age groups, and tend to visit their physician in the weeks preceding suicide death. To our knowledge, to date, no study has examined disturbed sleep as an independent risk factor for late-life suicide. OBJECTIVE To examine the relative independent risk for suicide associated with poor subjective sleep quality in a population-based study of older adults during a 10-year observation period. DESIGN, SETTING, AND PARTICIPANTS A longitudinal case-control cohort study of late-life suicide among a multisite, population-based community sample of older adults participating in the Established Populations for Epidemiologic Studies of the Elderly. Of 14 456 community older adults sampled, 400 control subjects were matched (on age, sex, and study site) to 20 suicide decedents. MAIN OUTCOMES AND MEASURES Primary measures included the Sleep Quality Index, the Center for Epidemiologic Studies–Depression Scale, and vital statistics. RESULTS Hierarchical logistic regressions revealed that poor sleep quality at baseline was significantly associated with increased risk for suicide (odds ratio [OR], 1.39; 95% CI, 1.14-1.69; P < .001) by 10 follow-up years. In addition, 2 sleep items were individually associated with elevated risk for suicide at 10-year follow-up: difficulty falling asleep (OR, 2.24; 95% CI, 1.27-3.93; P < .01) and nonrestorative sleep (OR, 2.17; 95% CI, 1.28-3.67; P < .01). Controlling for depressive symptoms, baseline self-reported sleep quality was associated with increased risk for death by suicide (OR, 1.30; 95% CI, 1.04-1.63; P < .05). CONCLUSIONS AND RELEVANCE Our results indicate that poor subjective sleep quality is associated with increased risk for death by suicide 10 years later, even after adjustment for depressive symptoms. Disturbed sleep appears to confer considerable risk, independent of depressed mood, for the most

[Predicting gainful employment in a population sample of 4225 statutory pension insurance members covering a prognostic period of five years using a brief subjective prognostic employment scale (SPE Scale)].

PubMed

Mittag, O; Meyer, T; Glaser-Möller, N; Matthis, C; Raspe, H

2006-05-01

Vocational (dis-)ability is a key concept in social medicine. It plays a major role in the realm of statutory pension funds (e. g. appraisal of applications for early retirement) as well as in epidemiologic or rehabilitation research. In a former population-based survey reliability of a short scale assessing the subjective prognosis of gainful employment (SPE-Scale, range = 0 - 3) had been tested. We now wanted to explore whether the SPE-Scale allows a prediction of vocational outcomes (early retirement) in the population sample over longer periods of time. Statutory pension insurees from Luebeck and surroundings aged between 40 and 55 were surveyed by questionnaire in 1999/2000. For 4225 subjects (= 95% of the original cohort) we obtained the following outcome data from pension fund records: dates of any applications for early retirement and beginning of retirement, date of death. The follow-up period covers 4.75 years on average. During this period 323 applications for early retirement (= 7.6%) were filed, and 200 subjects (= 4.7%) actually retired. First analysis including age and sex as covariates showed a threefold (SPE = 2) and eightfold (SPE = 3) risk of early retirement. Multivariate analysis (covariates: overall health status, number of chronic conditions, approved disability, subjective vocational ability, and length of sick leave measured at study onset) yielded a twofold risk of filing an application for early retirement (SPE = 3). The SPE-Scale is an appropriate screening instrument for hazards regarding gainful employment. It also can be recommended for use in epidemiologic or rehabilitation surveys.

Effect of silver-loaded PMMA on Streptococcus mutans in a drip flow reactor.

PubMed

Williams, Dustin L; Epperson, Richard Tyler; DeGrauw, Jeffery P; Nielsen, Mattias B; Taylor, Nicholas B; Jolley, Ryan D

2017-09-01

Orthodontic retention has been proposed as a life-long commitment for patients who desire to maintain straight teeth. However, the presence of foreign material increases risk of bacterial colonization and caries formation, of which Streptococcus mutans is a key contributor. Multiple studies have assessed the ability of silver to be added to base plate material and resist attachment of S. mutans. However, it does not appear that long-term washout in connection with biofilm growth under physiologically relevant conditions has been taken into consideration. In this study, silver was added to base plate material and exposed to short- or long-term washout periods. Materials were then assessed for their ability to resist biofilm formation of S. mutans using a drip flow reactor that modeled the human oral environment. Data indicated that silver was able to resist biofilm formation following short-term washout, but long-term washout periods resulted in a lack of ability to resist biofilm formation. These data will be important for future development of base plate materials to achieve long-term antimicrobial efficacy to reduce risk of caries formation and benefit patients in the long term. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2632-2639, 2017. © 2017 Wiley Periodicals, Inc.

Performance of 40- to 50-year-old subjects on a radar monitoring task : the effects of wearing bifocal glasses and interpolated rest periods on target detection time.

DOT National Transportation Integrated Search

1982-04-01

The present study examines the effects of wearing bifocal glasses and interpolated rest periods on the performance of 40- to 50-year-old subjects on a radar monitoring task. The visual display was designed to resemble an air traffic control radar dis...

High sensitive reflection type long period fiber grating biosensor for real time detection of thyroglobulin, a differentiated thyroid cancer biomarker: the Smart Health project

NASA Astrophysics Data System (ADS)

Quero, G.; Severino, R.; Vaiano, P.; Consales, M.; Ruvo, M.; Sandomenico, A.; Borriello, A.; Giordano, M.; Zuppolini, S.; Diodato, L.; Cutolo, A.; Cusano, A.

2015-09-01

We report the development of a reflection-type long period fiber grating (LPG) biosensor able to perform the real time detection of thyroid cancer markers in the needle washout of fine-needle aspiration biopsy. A standard LPG is first transformed in a practical probe working in reflection mode, then it is coated by an atactic-polystyrene overlay in order to increase its surrounding refractive index sensitivity and to provide, at the same time, the desired interfacial properties for a stable bioreceptor immobilization. The results provide a clear demonstration of the effectiveness and sensitivity of the developed biosensing platform, allowing the in vitro detection of human Thyroglobulin at sub-nanomolar concentrations.

Effect of food on the pharmacokinetics of triflusal and its major active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid, in healthy subjects.

PubMed

Ge, Jie; Ding, Li-Kun; Yang, Jing; Jia, Yan-yan; Lu, Cheng-tao; Ding, Yi; Song, Ying; Song, Wei; Wen, Ai-dong

2015-03-01

The objective of this study was to evaluate the pharmacokinetic parameters of triflusal and its major active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), following a single oral dose of 900 mg in healthy subjects under fed and fasting conditions. The study participants (n=12) were randomized to receive one 900 mg triflusal capsule in a fasting condition (no food for 12 hours) or a fed condition (after a high-fat meal); after a 2-week washout period, participants received the same dose of triflusal capsule under the converse condition. Pharmacokinetic parameters were calculated using WinNonlin 6.2 software. Safety was evaluated through assessment of adverse events, standard laboratory evaluations, vital signs, and 12-lead electrocardiography. The mean Cmax of triflusal and HTB were 13.96, 110.2 ug/mL for the fasting state and 9.546, 97.15 ug/mL for the fed state, respectively. The AUC0-144 of triflusal and HTB were 19.66, 5,572 hxμg/mL for the fasting state and 22.20, 5,038 hxμg/mL for the fed state, the AUC0-∞ of triflusal and HTB were 19.79, 6,333 hxμg/mL for the fasting state and 22.44, 5,632 hxμg/mL for the fed state, respectively. The results showed that Cmax and AUCs for triflusal were outside the bioequivalency (BE) interval after food intake, but there was no statistically significant change for HTB. High-fat food intake may affect the pharmacokinetics of triflusal capsule in healthy subjects.

A Phase 2 clinical trial of PF-05212377 (SAM-760) in subjects with mild to moderate Alzheimer's disease with existing neuropsychiatric symptoms on a stable daily dose of donepezil.

PubMed

Fullerton, Terence; Binneman, Brendon; David, William; Delnomdedieu, Marielle; Kupiec, James; Lockwood, Peter; Mancuso, Jessica; Miceli, Jeffrey; Bell, Joanne

2018-04-05

Symptomatic benefits have been reported for 5-HT 6 receptor antagonists in Alzheimer's disease (AD) trials. SAM-760 is a potent and selective 5-HT 6 receptor antagonist that has demonstrated central 5-HT 6 receptor saturation in humans at a dose of 30 mg. This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial evaluating the efficacy and safety of SAM-760 30 mg once daily (QD) for 12 weeks in subjects with AD on a stable regimen of donepezil 5 to 10 mg QD. The study included an interim analysis with stopping rules for futility or efficacy after 180 subjects completed the week 12 visit. Up to 342 subjects with AD (Mini-Mental State Examination (MMSE) score 10-24) and neuropsychiatric symptoms (Neuropsychiatric Inventory (NPI) total score ≥ 10) were to be enrolled if the study continued after the interim analysis. After a 4-week, single-blind, placebo run-in period, subjects entered the 12-week double-blind period and were randomized to either SAM-760 or placebo. The primary and key secondary efficacy endpoints were the change from baseline in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog13) and NPI total scores. Mixed models for repeated measures were used to analyze the data. At the interim analysis, when 186 subjects had been randomized and 163 had completed the week 12 visit, the study met futility criteria and was stopped. The mean week 12 treatment difference was 0.70 points (P = 0.43) for ADAS-cog13 and 2.19 points (P = 0.20) for NPI score, both of which were numerically in favor of placebo. Other secondary endpoints did not demonstrate any significant benefit for SAM-760. In total, 46.2% of SAM-760 subjects reported adverse events (AE) versus 44.7% for placebo, and there were 5 (5.5%) serious AEs in the SAM-760 group versus 3 (3.2%) for placebo. There were two deaths, one prior to randomization and one in the SAM-760 group (due to a traffic accident during washout of active treatment). SAM-760 was

The bioavailability and airway clearance of the steroid component of budesonide/formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial

PubMed Central

2009-01-01

Background Airway absorption and bioavailability of inhaled corticosteroids (ICSs) may be influenced by differences in pharmacokinetic properties such as lipophilicity and patient characteristics such as lung function. This study aimed to further investigate and clarify the distribution of budesonide and fluticasone in patients with severe chronic obstructive pulmonary disease (COPD) by measuring the systemic availability and sputum concentration of budesonide and fluticasone, administered via combination inhalers with the respective long-acting β2-agonists, formoterol and salmeterol. Methods This was a randomized, double-blind, double-dummy, two-way crossover, multicenter study. Following a run-in period, 28 patients with severe COPD (mean age 65 years, mean forced expiratory volume in 1 second [FEV1] 37.5% predicted normal) and 27 healthy subjects (mean age 31 years, FEV1 103.3% predicted normal) received two single-dose treatments of budesonide/formoterol (400/12 μg) and salmeterol/fluticasone (50/500 μg), separated by a 4–14-day washout period. ICS concentrations were measured over 10 hours post-inhalation in plasma in all subjects, and over 6 hours in spontaneously expectorated sputum in COPD patients. The primary end point was the area under the curve (AUC) of budesonide and fluticasone plasma concentrations in COPD patients relative to healthy subjects. Results Mean plasma AUC values were lower in COPD patients versus healthy subjects for budesonide (3.07 μM·hr versus 6.21 μM·hr) and fluticasone (0.84 μM·hr versus 1.50 μM·hr), and the dose-adjusted AUC (geometric mean) ratios in healthy subjects and patients with severe COPD for plasma budesonide and fluticasone were similar (2.02 versus 1.80; primary end point). In COPD patients, the Tmax and the mean residence time in the systemic circulation were shorter for budesonide versus fluticasone (15.5 min versus 50.8 min and 4.41 hrs versus 12.78 hrs, respectively) and Cmax was higher (1.08 �

Comparison of quantitative regional ventilation-weighted fourier decomposition MRI with dynamic fluorinated gas washout MRI and lung function testing in COPD patients.

PubMed

Kaireit, Till F; Gutberlet, Marcel; Voskrebenzev, Andreas; Freise, Julia; Welte, Tobias; Hohlfeld, Jens M; Wacker, Frank; Vogel-Claussen, Jens

2018-06-01

Ventilation-weighted Fourier decomposition-MRI (FD-MRI) has matured as a reliable technique for quantitative measures of regional lung ventilation in recent years, but has yet not been validated in COPD patients. To compare regional fractional lung ventilation obtained by ventilation-weighted FD-MRI with dynamic fluorinated gas washout MRI ( 19 F-MRI) and lung function test parameters. Prospective study. Twenty-seven patients with chronic obstructive pulmonary disease (COPD, median age 61 [54-67] years) were included. For FD-MRI and for 19 F-MRI a spoiled gradient echo sequence was used at 1.5T. FD-MRI coronal slices were acquired in free breathing. Dynamic 19 F-MRI was performed after inhalation of 25-30 L of a mixture of 79% fluorinated gas (C 3 F 8 ) and 21% oxygen via a closed face mask tubing using a dedicated coil tuned to 59.9 MHz. 19 F washout times in numbers of breaths ( 19 F-n breaths ) as well as fractional ventilation maps for both methods (FD-FV, 19 F-FV) were calculated. Slices were matched using a landmark driven algorithm, and only corresponding slices with an overlap of >90% were coregistered for evaluation. The obtained parameters were correlated with each other using Spearman's correlation coefficient (r). FD-FV strongly correlated with 19 F-n breaths on a global (r = -0.72, P < 0.0001) as well as on a lobar level and with lung function test parameters (FD-FV vs. FEV1, r = 0.76, P < 0.0001). There was a small systematic overestimation of FD-FV compared to 19 F-FV (mean difference -0.03 (95% confidence interval [CI]: -0.097; -0.045). Regional ventilation-weighted Fourier decomposition-MRI is a promising noninvasive, radiation-free tool for quantification of regional ventilation in COPD patients. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1534-1541. © 2017 International Society for Magnetic Resonance in Medicine.

29 CFR 783.47 - Off-duty periods.

Code of Federal Regulations, 2011 CFR

2011-07-01

... purpose. The fact that during such off-duty periods the employee is subject to call in case of emergency... 29 Labor 3 2011-07-01 2011-07-01 false Off-duty periods. 783.47 Section 783.47 Labor Regulations... EMPLOYED AS SEAMEN Computation of Wages and Hours § 783.47 Off-duty periods. Off-duty periods include not...

Inhibition of platelet function by low-dose plain and micro-encapsulated acetylsalicylic acid.

PubMed

Waldemar, G; Petersen, P; Boysen, G; Knudsen, J B

1988-04-15

The effect of two acetylsalicylic acid (ASA) formulations, plain (Magnyl) and micro-encapsulated (Globentyl), on platelet aggregation, thromboxane formation, and bleeding time was studied in 12 healthy volunteers in a randomized double-blind cross-over study. All subjects were treated with Magnyl and Globentyl (75 mg daily) in periods of 2 weeks, separated by a wash-out period of 2 weeks. Both drugs significantly depressed platelet aggregation and thromboxane formation and prolonged bleeding time without difference in mode of action of the drugs. It is concluded that significant inhibition of platelet activity may be achieved by low-dose ASA treatment with micro-encapsulated as well as with plain formulations.

Effect of pistachio consumption on plasma lipoprotein subclasses in pre-diabetic subjects.

PubMed

Hernández-Alonso, P; Salas-Salvadó, J; Baldrich-Mora, M; Mallol, R; Correig, X; Bulló, M

2015-04-01

Nuts have been demonstrated to improve several cardiovascular risk factors and the lipid profile in diabetic and pre-diabetic subjects. However, analysis of conventional serum lipid profiles does not completely explain the atherogenic risk associated with pre-diabetes. We therefore investigated whether chronic consumption of pistachio modifies the lipoprotein subclasses to a healthier profile in pre-diabetic subjects. Randomized cross-over clinical trial in 54 subjects with pre-diabetes. Subjects consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out. Diets were isocaloric and matched for protein, fiber and saturated fatty acids. Nuclear magnetic resonance (NMR) was performed to determine changes in plasma lipoprotein subclasses. Small low-density lipoprotein particles (sLDL-P) significantly decreased after pistachio consumption compared to the nut-free diet (P = 0.023). The non-high-density lipoprotein particles (non-HDL-P i.e. VLDL-P plus LDL-P) significantly decreased under the PD compared to CD (P = 0.041). The percentage of sHDL-P increased by 2.23% after the PD compared with a reduction of 0.08% after the CD (P = 0.014). Consequently, the overall size of HDL-P significantly decreased in the PD (P = 0.007). Chronic pistachio consumption could modify the lipoprotein particle size and subclass concentrations independently of changes in total plasma lipid profile, which may help to explain the decreased risk of cardiovascular disease and mortality associated with those individuals who frequently consumed nuts. This study is registered at www.clinicaltrials.gov as NCT01441921. Copyright © 2015 Elsevier B.V. All rights reserved.

First-phase insulin secretion has limited impact on postprandial glycemia in subjects with type 2 diabetes: correlations between hyperglycemic glucose clamp and meal test.

PubMed

Rave, Klaus; Sidharta, Patricia N; Dingemanse, Jasper; Heinemann, Lutz; Roggen, Kerstin

2010-02-01

Lack of first-phase insulin (INS) secretion is regarded as causative for high postprandial glucose excursions in subjects with type 2 diabetes. We aimed to determine the impact of early INS secretion on postprandial glycemia. Twenty subjects with type 2 diabetes (age 54 +/- 8 years, body mass index 28.7 +/- 2.7 kg/m(2) [mean +/- SD]) underwent a hyperglycemic glucose clamp and a meal test twice separated by a washout period of 4 weeks. Multiple regression analysis was used to identify determinants of postprandial glycemia. During hyperglycemic glucose clamps eight subjects showed a preserved first-phase INS secretion (P1+), whereas 12 subjects showed none (P1-). Both subject groups differed in fasting blood glucose (BG) (116 +/- 7 vs. 147 +/- 31 mg/dL, P = 0.011) and glycosylated hemoglobin (6.0 +/- 0.4 vs. 6.7 +/- 0.8, P = 0.041). Total INS secretory response during glucose clamps was higher in P1+ than P1- (INS-area under the concentration vs. time curve [AUC](0-120 min) 6.7 +/- 2.7 vs. 3.2 +/- 2.1 mU.min/mL; P = 0.006). During meal tests, however, INS-AUC(0-120 min) was similar between P1+ and P1-, whereas early INS secretion was still different (INS-AUC(0-60 min) 3.9 +/- 1.8 vs. 2.1 +/- 1.0 mU.min/mL; P = 0.031). Despite higher INS-AUC(0-60 min) in P1+, early postprandial BG was comparable between groups (BG-AUC(0-60 min) 1.5 +/- 0.5 vs. 1.6 +/- 0.6 g.min/dL; difference not significant). Multiple regression analyses showed no impact of first-phase INS secretion on postprandial glycemia, either in P1+ or in P1-. Nevertheless, in P1-, but not in P1+, postprandial glycemia was negatively correlated with INS sensitivity (R(2) = 0.83, P < 0.001). This study, correlating results of hyperglycemic glucose clamps with meal tests, shows that a preserved first-phase INS secretion has only a limited impact on postprandial glucose excursions in a group of subjects in early-stage type 2 diabetes.

Subjective and objective observation of skin graft recovery on Indonesian local cat with different periods of transplantation time.

PubMed

Erwin; Gunanti; Handharyani, Ekowati; Noviana, Deni

2016-05-01

The success of a skin graft in a cat is highly dependent on the granulation formed by the base of recipient bed. Granulation by the base of recipient bed will form after several days after injury. This research aimed to observe subjective and objective profile of skin graft recovery on forelimb of cats with different periods of donor skin placement. Nine male Indonesian local cats aged 1-2 years old, weighing 3-4 kg were divided into three groups. The first surgery for creating defect wound of 2 cm×2 cm in size was performed in the whole group. The wound was left for several days with the respective interval for each group, respectively: Group I (for 2 days), Group II (for 4 days), and Group III (for 6 days). In the whole group, the second surgery was done by the harvesting skin of thoracic area which then applied on recipient bed of respective groups. The donor skin on Group II was accepted faster compared to Group I and Group III. The donor skin did not show color differences compared to surrounding skin, painless, bright red in bleeding test had faster both hair growth and drug absorption. Test toward the size of donor skin and the effect of drugs did not show a significant difference between each group. The observe subjective and objective profile of skin graft recovery on forelimb of cats on Group II were accepted faster compared to Group I and III.

Steady-state phase error for a phase-locked loop subjected to periodic Doppler inputs

NASA Technical Reports Server (NTRS)

Chen, C.-C.; Win, M. Z.

1991-01-01

The performance of a carrier phase locked loop (PLL) driven by a periodic Doppler input is studied. By expanding the Doppler input into a Fourier series and applying the linearized PLL approximations, it is easy to show that, for periodic frequency disturbances, the resulting steady state phase error is also periodic. Compared to the method of expanding frequency excursion into a power series, the Fourier expansion method can be used to predict the maximum phase error excursion for a periodic Doppler input. For systems with a large Doppler rate fluctuation, such as an optical transponder aboard an Earth orbiting spacecraft, the method can be applied to test whether a lower order tracking loop can provide satisfactory tracking and thereby save the effect of a higher order loop design.

Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: a randomized, double blind, crossover study.

PubMed

Cabo, Rona; Hernes, Sigrunn; Slettan, Audun; Haugen, Margaretha; Ye, Shu; Blomhoff, Rune; Mansoor, M Azam

2015-05-01

Data on the effect of combined genetic polymorphisms, involved in folate metabolism, on the concentration of serum folate after folic acid supplementation are scarce. Therefore, we investigated the impact of seven gene polymorphisms on the concentration of serum folate and p-tHcy in healthy subjects after short-term folic acid supplementation. In a randomized, double blind, crossover study, apparently healthy subjects were given either 0.8 mg folic acid per day (n = 46) or placebo (n = 45) for 14 days. The washout period was 14 days. Fasting blood samples were collected on day 1, 15, 30 and 45. Data on subjects on folic acid supplementation (n = 91) and on placebo (n = 45) were used for the statistical analysis. The concentration of serum folate increased higher in subjects with higher age (53.5 ± 7.0 years) than in subjects with lower age (24.3 ± 3.2 years) after folic acid supplementation (p = 0.006). The baseline concentration of serum folate in subjects with polymorphism combination, reduced folate carrier protein, RFC1-80 GA and methylenetetrahydrofolate reductase, MTHFR677 CT+TT, was lower than RFC1-80 AA and MTHFR677 CT+TT (p = 0.002). After folic acid supplementation, a higher increase in the concentration of serum folate was detected in subjects with polymorphism combination RFC1-80 GA and MTHFR677 CC than RFC1-80 GG and MTHFR CT+TT combination (p < 0.0001). The baseline concentration of plasma total homocysteine (p-tHcy) was altered by combined polymorphisms in genes associated with folate metabolism. After folic acid supplementation, in subjects with combined polymorphisms in methylenetetrahydrofolate dehydrogenase, MTHFD1-1958 and MTHFR-677 genes, the concentration of p-tHcy was changed (p = 0.002). The combination of RFC1-80 and MTHFR-677 polymorphisms had a profound affect on the concentration of serum folate in healthy subjects before and after folic acid supplementation.

Relative bioequivalence evaluation of two oral atomoxetine hydrochloride capsules: a single dose, randomized, open-label, 2-period crossover study in healthy Chinese volunteers under fasting conditions.

PubMed

Shang, D-W; Guo, W; Zhou, F-C; Wang, X-P; Li, A-N; Zhang, L; Li, W-B; Lu, W; Wang, C-Y

2013-11-01

To evaluate the bioequivalence of a new formulation of atomoxetine hydrochloride (CAS 82248-59-7) capsules (test) and an available branded capsules (reference) after administration of a single 40 mg dose, randomized, open-label, 2-period crossover study was conducted in 22 healthy male Chinese subjects with a 1-week wash-out period. This study was designed for/the Honglin Pharmaceutical Co. Ltd and contracted to be done by the Beijing Anding Hospital in order to satisfy Chinese regulatory requirements to allow marketing of this generic product and performed according to the criteria of SFDA. Blood samples were collected before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16 and 24 h after drug administration. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) with UV detection. A non-compartmental method was used to calculate the pharmacokinetic parameters and evaluate bioequivalence of the 2 formulations. The 90% confidence interval (CI) of the ratios (test/reference) of atomoxetine for AUC0-24, AUC0-∞ and Cmax were 100.9% (93.6-108.8%), 103.1% (95.1-111.7%) and 105.2% (92.8-119.4%), respectively, which fell within the interval of 80-125% and 75-133%. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. From these results it can be concluded that the test formulation of atomoxetine capsules met the regulatory criterion for bioequivalence to the reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

46 CFR 403.115 - Accounting period.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Accounting period. 403.115 Section 403.115 Shipping COAST GUARD (GREAT LAKES PILOTAGE), DEPARTMENT OF HOMELAND SECURITY GREAT LAKES PILOTAGE UNIFORM ACCOUNTING SYSTEM General § 403.115 Accounting period. Each Association subject to this part shall maintain...

Diagnosis of vasculogenic impotence: Combination of penile xenon-133 washout and papaverine tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, S.N.; Liu, R.S.; Yu, P.C.

1989-07-01

The present study evaluates both penile xenon-133 washout (XWT) and papaverine tests (PT) in the diagnosis of vasculogenic impotence. XWT was accomplished by subcutaneous injection of xenon-133 (1-2 mCi in 0.1 mL saline solution) into the dorsal coronal prepuce. Abnormal XWT was suggested in patients whose clearance time (T1/2) was longer than 7.5 minutes and whose penile blood flow rate (Q) was less than 6 mL/100 g tissue/min. PT was done by intracavernous injection of papaverine (60 mg in 20 mL normal saline). Abnormal PT was indicated in patients whose onset of full erection was more than ten minutes aftermore » papaverine injection and whose duration of erection was less than one hour. Ten young and 11 older normal volunteers were examined with XWT only; all showed normal results. A total of 60 impotent patients were examined with both XWT and PT and were classified into four groups: in 2 patients (3.3%) both XWT and PT were normal (group I); in 8 (13.3%) XWT was abnormal and PT normal (group II); in 14 (23.3%) XWT was normal and PT abnormal (group III); and in 36 (60%) both XWT and PT were abnormal (group IV). On further examination with bilateral hypogastric arteriography in 10 XWT-abnormal patients and on surgical correction of abnormal curvature in 5 XWT-abnormal patients, all (100%) were proved to have penile arterial insufficiency. Erection cavernosography performed in 15 PT-abnormal patients confirmed penile venous insufficiency in 80 percent. We conclude both XWT and PT are simple and effective for evaluation of the penile arterial blood flow and venous competence, respectively.« less

Evaluation of a dental floss containing soluble pyrophosphate on calculus formation using a short-term clinical model.

PubMed

Kleber, C J; Putt, M S; Milleman, J L; Harris, M

1998-01-01

This clinical study compared the effect of a dental floss containing 0.25 mg tetrasodium pyrophosphate per cm and a placebo floss on supragingival calculus formation using a 6-week, partial-mouth toothshield model. The six lower anterior teeth were scaled and polished before each 2-week period (i.e., pre-trial, washout, trial). During both the pre-trial and trial periods, subjects brushed twice daily with a non-tartar control dentifrice, while a toothshield protected the six test teeth from brushing. After rinsing with water and removing the shield, they flossed the test teeth. All subjects used placebo floss during the pre-trial period in order to determine the baseline Volpe-Manhold Index (VMI) calculus formation scores, which were used to balance groups for the trial period. During the trial period, one group used the placebo floss, while the second group used the pyrophosphate floss. The final results demonstrated that the pyrophosphate floss significantly inhibited calculus formation between teeth (mesial-distal scores) by 21%, and on labial surfaces by 37% relative to the placebo floss.

Assessment of pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers.

PubMed

Lim, Mi-sun; Seong, Sook Jin; Park, Jeonghyeon; Seo, Jeong Ju; Lee, Joomi; Yu, Kyung-Sang; Lee, Hae Won; Yoon, Young-Ran

2012-04-01

Levofloxacin and cyclosporine show different pharmacokinetic properties, but are known to be dose proportional within the therapeutic range. The authors evaluated the pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers, by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two independent, randomized, crossover studies were performed. For levofloxacin, eight volunteers were randomly assigned in a 1:1 ratio to receive a low dose (7.5 mg) orally or intravenously, followed by a 1-week washout period and administration via the alternate route. After another 1-week washout period, a therapeutic dose (750 mg) was administered to all eight subjects. For cyclosporine, another eight volunteers received a low dose (2 mg) or a therapeutic dose (200 mg) orally with a 1-week washout period. Drug concentrations were determined by LC-MS/MS. For levofloxacin, the mean values for dose-normalized C(max) and AUC(last) with the two doses were as follows: therapeutic dose, 15.2 ± 4.6 ng/ml/mg and 103.6 ± 15.5 ng·h/ml/mg, respectively; low dose, 17.1 ± 6.5 ng/ml/mg and 72.6 ± 8.7 ng·h/ml/mg, respectively. For cyclosporine, the mean values for dose-normalized C(max) and AUC(last) were as follows: therapeutic dose, 4.9 ± 1.5 ng/ml/mg and 15.4 ± 4.9 ng·h/ml/mg, respectively; low dose, 1.6 ± 0.6 ng/ml/mg and 9.3 ± 7.3 ng·h/ml/mg, respectively. In this study levofloxacin, which is completely absorbed and primarily eliminated renally without modification, showed better pharmacokinetic proportionality than cyclosporine, which is poorly absorbed and extensively metabolized.

Endothelial function in patients with migraine during the interictal period.

PubMed

Silva, Federico A; Rueda-Clausen, Christian F; Silva, Sandra Y; Zarruk, Juan G; Guzmán, Juan C; Morillo, Carlos A; Vesga, Boris; Pradilla, Gustavo; Flórez, Mildred; López-Jaramillo, Patricio

2007-01-01

The aim of this study is to evaluate endothelial function in migraineurs subjects during the asymptomatic period. Migraine has been proposed as a risk factor for cerebrovascular events. The underlying mechanisms that relate these 2 pathologies are unknown. Nitric oxide (NO) has been proposed as the final causative molecule of migraine. Increased NO metabolites concentrations have been reported in migraineurs subjects during acute migraine attacks, but there is no evidence indicating alterations in endothelial NO release during the symptom free period in theses subjects. Fifty migraineurs subjects and 25 healthy subjects matched by gender and age were included. Every subject underwent a complete examination that included medical history, physical examination, resting electrocardiogram, forearm flow-mediated vasodilation (FMD), blood determinations of fasting nitrates and nitrites (NO(2) (-)+ NO(3) (-)), glucose, lipid profile, creatinine, C-reactive protein, and blood cell count. No differences in FMD or NO(2) (-)+ NO(3) (-) were detected among groups. The only difference between migraineurs and control subjects was a higher mean blood pressure 92.1 (8.8) mmHg versus 86.7 (8.2) mmHg P= .01. The endothelial function is not altered during the interictal period in migraineurs subjects.

Effects of alcohol and energy drink on mood and subjective intoxication: a double-blind, placebo-controlled, crossover study.

PubMed

Benson, Sarah; Scholey, Andrew

2014-07-01

There is concern that combining energy drinks with alcohol may 'mask' subjective intoxication leading to greater alcohol consumption. This study examines the effects of alcohol alone and combined with energy drink on objective and subjective intoxication and mood over the course of 3 h. Using a double-blind, placebo-controlled, balanced, crossover design, 24 participants (mean age 22.23 years) were administered with double placebo, 0.6 g/kg alcohol (mean peak blood alcohol content of 0.051%), 250 ml energy drink and alcohol/energy drink, according to a Latin square design, with a washout of >48 h. On each visit, they were breathalysed and rated themselves on a comprehensive battery of mood items at baseline and then at 45, 90 and 180 min post-drink. Blood alcohol and subjective intoxication were significantly increased following both alcohol alone and alcohol/energy drink. Both measures were statistically indistinguishable between alcohol conditions. In keeping with its (80 mg) caffeine content, the energy drink alone significantly increased self-rated 'alertness' and reduced 'depression-dejection' scores compared with the combined alcohol/energy drink. The alcohol/energy drink increased 'vigor' and 'contentment' at 45 min and decreased 'contentment' at 180 min. The co-ingestion of an energy drink with alcohol does not differently influence blood alcohol content recordings or subjective intoxication compared with alcohol alone, although some mood items are differentially affected. Copyright © 2014 John Wiley & Sons, Ltd.

Transient statistics in stabilizing periodic orbits

NASA Astrophysics Data System (ADS)

Meucci, R.; Gadomski, W.; Ciofini, M.; Arecchi, F. T.

1995-11-01

The statistics of chaotic and periodic transient time intervals preceding the stabilization of a given periodic orbit have been experimentally studied in a CO2 laser with modulated losses, subjected to a small subharmonic perturbation. As predicted by the theory, an exponential tail has been found in the probability distribution of chaotic transients. Furthermore, a fine periodic structure in the distributions of the periodic transients, resulting from the interaction of the control signal and the local structure of the chaotic attractor, has been revealed.

Analysis of the antibacterial activity and plaque control benefit of colgate total dentifrice via clinical evaluation and real-time polymerase chain reaction.

PubMed

Xu, Tao; Deshmukh, Meenal; Barnes, Virginia Monsul; Trivedi, Harsh M; Du-Thumm, Laurence; Richter, Rose; Cummins, Diane

2005-01-01

This study analyzed, from a combined clinical and molecular biologic perspective, the antibacterial and antiplaque efficacy of Colgate Total dentifrice (CTD). A single-blind crossover study design utilized 11 healthy human subjects. After a one-week washout period, subjects donated dental plaque, received a dental prophylaxis, and subsequently brushed with a test product. Twenty-four hours postbrushing, dental plaque was collected and a clinical plaque score determined. Dental plaque was submitted for Real-time Polymerase Chain Reaction (Real-time PCR) analysis. The same procedure was repeated in accordance with a crossover design for the use of the second test product. Following a one-week washout, a plaque donation, prophylaxis, and brushing with the test product ensued for each subject. Twenty-four hours post-brushing, the subjects returned for a plaque score and plaque donation. Twenty-four hours after brushing, dental plaque coverage increased 17.88% +/- 8.27% with CTD, compared to 30.42% +/- 9.97% with Colgate Cavity Protection (CCP; p = 0.005). Real-time PCR found plaque collected 24 hours after brushing with CTD exhibited, on average, fewer representative periodontal pathogens (Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans, Tannerella forsythensis, and Porphyromonas gingivalis) and fewer early colonizers (Actinomyces naeslundii) than plaque collected before brushing, whereas CCP showed a moderate effect on oral bacteria. The study provides clinical and molecular biological evidence to substantiate the antibacterial and plaque control benefits of Colgate Total, and suggests the value of combining a molecular biological method with clinical research to corroborate clinical benefits.

Crypto-periodicity in Mansonella ozzardi.

PubMed

Pichon, G

1983-01-01

Studying nycthemeral microfilarial density in eight carriers of Mansonella ozzardi, Nathan et al. concluded that there is an absence of periodicity in M. ozzardi in Trinidad. Re-examination of the results obtained shows evidence of crypto-periodicity. Two of the eight patients showed highly significant periodicity but the biorhythms appear to be almost out of phase, the respective peaks being at 18.00 hours and 02.00 hours. The six other patients showed no obvious periodicity; the calculated acrophases (peak hours), instead of being randomly spaced, regrouped with the preceding ones: late afternoon in two subjects and in the second half of the night for the other four. It is concluded that the apparent non-periodicity is due to the co-existence of two periodic forms, but these are markedly out of phase.

Acute systemic effects of inhaled salbutamol in asthmatic subjects expressing common homozygous beta2-adrenoceptor haplotypes at positions 16 and 27.

PubMed

Lee, Daniel K C; Bates, Caroline E; Lipworth, Brian J

2004-01-01

The relationship between beta2-adrenoceptor polymorphisms at positions 16 and 27, and the acute systemic beta2-adrenoceptor effects of inhaled salbutamol is unclear. We therefore elected to evaluate the influence of common homozygous beta2-adrenoceptor haplotypes on the acute systemic beta2-adrenoceptor effects following inhaled salbutamol in asthmatic subjects. An initial database search of 531 asthmatic subjects identified the two commonest homozygous haplotypes at positions 16 and 27 to be Arg16-Gln27 (12%) and Gly16-Glu27 (19%). After a 1-week washout period where all beta2-adrenoceptor agonists were withdrawn, 16 Caucasian subjects (Arg16-Gln27: n = 8 and Gly16-Glu27: n = 8) were given a single dose of inhaled salbutamol (1200 microg), followed by serial blood sampling for serum potassium, along with measurements of diastolic blood pressure and heart rate, at 5-min intervals for 20 min. The two groups were well matched for age, sex, FEV1, and inhaled corticosteroid dose. Baseline values for serum potassium, diastolic blood pressure and heart rate were not significantly different comparing Arg16-Gln27 vs Gly16-Glu27. The mean +/- SEM maximum serum potassium change from baseline over 20 min was significantly greater (P = 0.04) for Arg16-Gln27: -0.37 +/- 0.05 mmol l(-1) vs Gly16-Glu27: -0.23 +/- 0.04 mmol l(-1); 95% CI for difference: -0.01 to -0.28 mmol l(-1). The maximum diastolic blood pressure change from baseline over 20 min was significantly greater (P = 0.0008) for Arg16-Gln27: -13 +/- 1 mmHg vs Gly16-Glu27: -4 +/- 2 mmHg; 95% CI for difference: -5, 14 mmHg. There was no significant difference comparing the maximum heart rate change from baseline for Arg16-Gln27: 10 +/- 3 beats min(-1) vs Gly16-Glu27: 10 +/- 3 beats min(-1). Caucasian asthmatic subjects with the Arg16-Gln27 haplotype exhibited a greater systemic response to inhaled salbutamol, compared with those with the Gly16-Glu27 haplotype. The attenuated beta2-adrenoceptor response in the Gly16-Glu27

Haemodynamic and hormonal effects of cilazapril in comparison with propranolol in healthy subjects and in hypertensive patients

PubMed Central

Kleinbloesem, C. H.; Erb, K.; Essig, J.; Breithaupt, K.; Belz, G. G.

1989-01-01

1 The purpose of the present studies was to compare the pharmacodynamic profile of the new ACE inhibitor cilazapril with the β-adrenoceptor antagonist propranolol in healthy subjects and in hypertensive patients. 2 Hormonal and haemodynamic responses at rest and after pharmacological interventions with angiotensin I and isoprenaline were investigated in six healthy volunteers following a 1 week treatment with placebo, propranolol (120 mg day-1) and cilazapril (2.5 mg day-1) in a double-blind cross over design with a wash-out period of 1 week between the different treatments. 3 Cilazapril induced a pronounced increase of plasma renin activity and angiotensin I concentrations, whereas after propranolol both parameters decreased. After both compounds slight decreases in angiotensin II concentrations were found. After the pharmacological challenges with angiotensin I and isoprenaline specific effects of the ACE inhibitor and β-adrenoceptor blocker were found respectively. 4 Seventeen hypertensive patients received after a 2 week placebo period in random order cilazapril (2.5 mg day-1) or propranolol (120 mg day-1) for 3 weeks. A cross over design switched the patients to the other treatment. On the last day of each treatment period blood pressure, heart rate, cardiac output and total peripheral resistance were determined at rest and during handgrip test. In addition, bicycle exercise test was done and blood lactate concentrations were determined. 5 At rest blood pressure was lowered by both drugs, but total peripheral resistance increased after propranolol and decreased after cilazapril. After hand grip test, blood pressure was lowered after both drugs, but peripheral resistance decreased only after cilazapril. After bicycle exercise the median maximal exercise was 175 W after cilazapril and 150 W after propranolol, whereas lactate concentrations were higher in the propranolol group. 6 It could be concluded that cilazapril and propranolol suppressed the renin

Clinical application of inert gas Multiple Breath Washout in children and adolescents with asthma.

PubMed

Zwitserloot, Annelies; Fuchs, Susanne I; Müller, Christina; Bisdorf, Kornelia; Gappa, Monika

2014-09-01

Children with asthma often have normal spirometry despite significant disease. The pathology of the small airways in asthma may be assessed using Multiple Breath Washout (MBW) and calculating the Lung Clearance Index (LCI). There are only few studies using MBW in children with asthma and existing data regarding bronchodilator effect are contradictory. The aim of the present pilot study was to compare LCI in asthma and controls and assess the effect of salbutamol in children with asthma on the LCI. Unselected patients with a diagnosis of asthma visiting the outpatient department of our hospital between 04-2010 and 03-2011 were recruited and compared to a healthy control group. MBW was performed as inert gas MBW using sulfurhexafluorid (SF6) as the tracer gas. Clinical data were documented and spirometry and MBW (EasyOne Pro, MBW module, NDD Switzerland) were performed before and after the use of salbutamol (200-400 μg). Healthy controls performed baseline MBW only. 32 children diagnosed with asthma (4.7-17.4 years) and 42 controls (5.3-20.8) were included in the analysis. LCI differed between patients and controls, with a mean LCI (SD) of 6.48 (0.48) and 6.21 (0.38) (P = 0.008). Use of salbutamol had no significant effect on LCI for the group. These pilot data show that clinically stable asthma patients and controls both have a LCI in the normal range. However, in patients the LCI is significantly higher indicating that MBW may have a role in assessing small airways disease in asthma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Beneficial effects of viscous dietary fiber from Konjac-mannan in subjects with the insulin resistance syndrome: results of a controlled metabolic trial.

PubMed

Vuksan, V; Sievenpiper, J L; Owen, R; Swilley, J A; Spadafora, P; Jenkins, D J; Vidgen, E; Brighenti, F; Josse, R G; Leiter, L A; Xu, Z; Novokmet, R

2000-01-01

Dietary fiber has recently received recognition for reducing the risk of developing diabetes and heart disease. The implication is that it may have therapeutic benefit in prediabetic metabolic conditions. To test this hypothesis, we investigated the effect of supplementing a high-carbohydrate diet with fiber from Konjac-mannan (KJM) on metabolic control in subjects with the insulin resistance syndrome. We screened 278 free-living subjects between the ages of 45 and 65 years from the Canadian-Maltese Diabetes Study. A total of 11 (age 55+/-4 years, BMI 28+/-1.5 kg/m2) were recruited who satisfied the inclusion criteria: impaired glucose tolerance, reduced HDL cholesterol, elevated serum triglycerides, and moderate hypertension. After an 8-week baseline, they were randomly assigned to take either KJM fiber-enriched test biscuits (0.5 g of glucomannan per 100 kcal of dietary intake or 8-13 g/day) or wheat bran fiber (WB) control biscuits for two 3-week treatment periods separated by a 2-week washout. The diets were isoenergetic, metabolically controlled, and conformed to National Cholesterol Education Program Step 2 guidelines. Serum lipids, glycemic control, and blood pressure were the outcome measures. Decreases in serum cholesterol (total, 12.4+/-3.1%, P<0.004; LDL, 22+/-3.9%, P<0.002; total/HDL ratio, 15.2+/-3.4%, P<0.003; and LDL/HDL ratio, 22.2+/-4.1%, P< 0.002), apolipoprotein (apo) B (15.1+/-4.3%, P<0.0004), apo B/A-1 ratio (13.1+/-3.4%, P< 0.0003), and serum fructosamine (5.2+/-1.4%, P<0.002) were observed during KJM treatment compared with WB-control. Fasting blood glucose, insulin, triglycerides, HDL cholesterol, and body weight remained unchanged. A diet rich in high-viscosity KJM improves glycemic control and lipid profile, suggesting a therapeutic potential in the treatment of the insulin resistance syndrome.

Clinically-relevant consecutive treatment with isoproterenol and adenosine protects the failing heart against ischaemia and reperfusion

PubMed Central

2014-01-01

Background Consecutive treatment of normal heart with a high dose of isoproterenol and adenosine (Iso/Ade treatment), confers strong protection against ischaemia/reperfusion injury. In preparation for translation of this cardioprotective strategy into clinical practice during heart surgery, we further optimised conditions for this intervention using a clinically-relevant dose of Iso and determined its cardioprotective efficacy in hearts isolated from a model of surgically-induced heart failure. Methods Isolated Langendorff-perfused rat hearts were treated sequentially with 5 nM Iso and 30 μM Ade followed by different durations of washout prior to 30 min global ischaemia and 2 hrs reperfusion. Reperfusion injury was assessed by measuring haemodynamic function, lactate dehydrogenase (LDH) release and infarct size. Protein kinase C (PKC) activity and glycogen content were measured in hearts after the treatment. In a separate group of hearts, Cyclosporine A (CsA), a mitochondria permeability transition pore (MPTP) inhibitor, was added with Iso/Ade. Failing hearts extracted after 16 weeks of ligation of left coronary artery in 2 months old rats were also subjected to Iso/Ade treatment followed by ischaemia/reperfusion. Results Recovery of the rate pressure product (RPP) in Iso/Ade-treated hearts was significantly higher than in controls. Thus in Iso/Ade treated hearts with 5 nM Iso and no washout period, RPP recovery was 76.3 ± 6.9% of initial value vs. 28.5 ± 5.2% in controls. This was associated with a 3 fold reduction in LDH release irrespective to the duration of the washout period. Hearts with no washout of the drugs (Ade) had least infarct size, highest PKC activity and also showed reduced glycogen content. Cardioprotection with CsA was not additive to the effect of Iso/Ade treatment. Iso/Ade treatment conferred significant protection to failing hearts. Thus, RPP recovery in failing hearts subjected to the treatment was 69.0 ± 16.3% while in

Effect of a Synbiotic Yogurt on Levels of Fecal Bifidobacteria, Clostridia, and Enterobacteria

PubMed Central

Palaria, Amrita; Johnson-Kanda, Ivy

2012-01-01

While ingestion of synbiotic yogurts containing Bifidobacterium animalis subsp. lactis and inulin is increasing, their effect on certain microbial groups in the human intestine is unclear. To further investigate this, a large-scale, crossover-design, placebo-controlled study was utilized to evaluate the effect of a synbiotic yogurt containing B. animalis subsp. lactis Bb-12 and inulin on the human intestinal bifidobacteria, clostridia, and enterobacteria. Fecal samples were collected at 14 time points from 46 volunteers who completed the study, and changes in the intestinal bacterial levels were monitored using real-time PCR. Strain Bb-12 could not be detected in feces after 2 weeks of washout. A live/dead PCR procedure indicated that the Bb-12 strain detected in the fecal samples was alive. A significant increase (P < 0.001) in the total bifidobacterial numbers was seen in both groups of subjects during the final washout period compared to the prefeeding period. This increase in total bifidobacteria corresponded with a significant decrease (P < 0.05) in numbers of clostridia but not enterobacteria. No significant differences in numbers of bifidobacteria, clostridia, or enterobacteria were observed between the probiotic and placebo groups during any of the feeding periods. However, subgrouping subjects based on lower initial bifidobacterial numbers or higher initial clostridial numbers did show corresponding significant differences between the synbiotic yogurt and placebo groups. This was not observed for a subgroup with higher initial enterobacterial numbers. While this synbiotic yogurt can increase bifidobacterial numbers and decrease clostridial numbers (but not enterobacterial numbers) in some individuals, it cannot modulate these microbial groups in the majority of individuals. PMID:22101054

Multiple breath washout with a sidestream ultrasonic flow sensor and mass spectrometry: a comparative study.

PubMed

Fuchs, Susanne I; Buess, Christian; Lum, Sooky; Kozlowska, Wanda; Stocks, Janet; Gappa, Monika

2006-12-01

Over recent years, there has been renewed interest in the multiple breath wash-out (MBW) technique for assessing ventilation inhomogeneity (VI) as a measure of early lung disease in children. While currently considered the gold standard, use of mass spectrometry (MS) to measure MBW is not commercially available, thereby limiting widespread application of this technique. A mainstream ultrasonic flow sensor was marketed for MBW a few years ago, but its use was limited to infants. We have recently undertaken intensive modifications of both hardware and software for the ultrasonic system to extend its use for older children. The aim of the current in vivo study was to compare simultaneous measurements of end-tidal tracer gas concentrations and lung clearance index (LCI) from this modified ultrasonic device with those from a mass spectrometer. Paired measurements of three MBW, using 4% sulfur hexafluoride (SF(6)) as the tracer gas and the two systems in series, were obtained in nine healthy adult volunteers. End-tidal tracer gas concentrations (n = 675 paired values) demonstrated close agreement (95% CI of difference -0.23; -0.17%, r(2) = 1). FRC was slightly higher from the MS (95%CI 0.08;0.17 L), but there was no difference in LCI (95%CI -0.10; 0.3). We conclude, that this ultrasonic prototype system measures end-tidal tracer gas concentration accurately and may therefore be a valid tool for MBW beyond early childhood. This prototype system could be the basis for a commercial device allowing more widespread application of MBW in the near future.

Field studies of pine, spruce and aspen periodically subjected to sulfur gas emissions

Treesearch

A. H. Legge; R. G. Amundson; D. R. Jaques; R. B. Walker

1976-01-01

Field studies of photosynthesis in Pinus contorta/Pinus banksiana (lodgepole pine/jack pine) hybrids, Picea glauca (white spruce) and Populus tremuloides (aspen) subjected to SO2 and H2S from a nearby natural gas processing plant were initiated near Whitecourt,...

Electrogastrograms during motion sickness in fasted and fed subjects

NASA Technical Reports Server (NTRS)

Stewart, John J.; Wood, Mary J.; Wood, Charles D.

1989-01-01

Seven human volunteers were subjected to stressful Coriolis stimulation (rotating chair) either during the fasted state or following the ingestion of yogurt (6 oz). Subjects tested after yogurt reached a malaise-III (M-III) endpoint of motion sickness after significantly (p smaller than 0.01) fewer head movements than subjects tested in the fasted state. Surface electrogastrogram (EGG) recordings at M-III were similar for both dietary stats and consisted of a brief period of tachygastria, followed by a period of low-amplitude EGG waves. Ingestion of yogurt enhanced susceptibility to motion sickness but did not affect the associated pattern of EGG.

Comparison of sevelamer and calcium carbonate on endothelial function and inflammation in patients on peritoneal dialysis.

PubMed

Chennasamudram, Sudha P; Noor, Tanjila; Vasylyeva, Tetyana L

2013-06-01

Hyperphosphataemia is a known independent risk factor for cardiovascular mortality. The objective of the study was to compare the effects of two phosphate binders, sevelamer carbonate and calcium carbonate on endothelial function (EF) and inflammation in patients on peritoneal dialysis (PD) with Type 2 diabetes mellitus (T2DM). Fifteen subjects with hyperphosphataemia discontinued all phosphate binders to undergo a two-week washout and were assigned to sevelamer carbonate or calcium carbonate treatments for eight weeks. After a second two-week washout period, subjects crossed over to either of the alternate treatments for another eight weeks. At the beginning and end of each treatment, biomarkers of EF, pro-inflammatory cytokines, serum albumin, calcium, phosphate and lipids were measured. Sevelamer carbonate significantly improved lipid profile compared with calcium carbonate. Amongst the EF and pro-inflammatory biomarkers, sevelamer carbonate decreased serum endothelin-1, plasminogen activator inhibitor-1, C-reactive protein and interleukin-6. Both phosphate binders were effective in decreasing serum phosphate but sevelamer had a positive effect on EF. Treatment with sevelamer carbonate has beneficial effects compared with calcium carbonate in decreasing inflammation and improving EF in patients with T2DM on PD. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Phase synchronization of baroclinic waves in a differentially heated rotating annulus experiment subject to periodic forcing with a variable duty cycle

NASA Astrophysics Data System (ADS)

Read, P. L.; Morice-Atkinson, X.; Allen, E. J.; Castrejón-Pita, A. A.

2017-12-01

A series of laboratory experiments in a thermally driven, rotating fluid annulus are presented that investigate the onset and characteristics of phase synchronization and frequency entrainment between the intrinsic, chaotic, oscillatory amplitude modulation of travelling baroclinic waves and a periodic modulation of the (axisymmetric) thermal boundary conditions, subject to time-dependent coupling. The time-dependence is in the form of a prescribed duty cycle in which the periodic forcing of the boundary conditions is applied for only a fraction δ of each oscillation. For the rest of the oscillation, the boundary conditions are held fixed. Two profiles of forcing were investigated that capture different parts of the sinusoidal variation and δ was varied over the range 0.1 ≤δ≤1 . Reducing δ was found to act in a similar way to a reduction in a constant coupling coefficient in reducing the width of the interval in forcing frequency or period over which complete synchronization was observed (the "Arnol'd tongue") with respect to the detuning, although for the strongest pulse-like forcing profile some degree of synchronization was discernible even at δ=0.1 . Complete phase synchronization was obtained within the Arnol'd tongue itself, although the strength of the amplitude modulation of the baroclinic wave was not significantly affected. These experiments demonstrate a possible mechanism for intraseasonal and/or interannual "teleconnections" within the climate system of the Earth and other planets that does not rely on Rossby wave propagation across the planet along great circles.

A Randomized Clinical Study to Evaluate the Effect of Two Experimental Toothpastes on Tooth Enamel Gloss and Smoothness.

PubMed

Milleman, Kimberly R; Milleman, Jeffery L; Creeth, Jonathan E; Butler, Andrew; Bosma, Mary Lynn

2016-03-01

The study compared the effects on examiner-assessed tooth gloss and smoothness of two experimental toothpastes (1% or 2% alumina abrasive) with a reference, silica-based toothpaste used twice daily for one, four, and eight weeks. The study also monitored the safety of the products. This was a randomized, examiner-blind study, stratified by gloss score and age, three-treatment, parallel-group using healthy adult volunteers. Following a two-week washout period where subjects brushed with a conventional silica-abrasive toothpaste, 169 subjects began the trial period after receiving a dental scaling and polishing using the washout toothpaste. Subjects brushed for two minutes, twice daily, with their assigned toothpaste. The experimental toothpastes contained 927 ppm fluoride as NaF with either 1% or 2% alumina as the sole abrasive. The reference toothpaste contained 927 ppm fluoride as NaF in a conventional amorphous silica abrasive base. Enamel polish (i.e., gloss) was assessed visually by comparing the facial surfaces of the maxillary incisors with a set of standards. Tooth smoothness was assessed by lightly dragging a dental explorer over the surface. Subjects using the 2% alumina toothpaste had significantly higher gloss compared to the reference toothpaste at Weeks 1 and 4, but the difference was of borderline significance at Week 8 (one-covariate analysis: p = 0.0529; two-covariate analysis: p = 0.0494). Subjects using the 1% alumina toothpaste had significantly higher gloss improvement scores than the reference toothpaste at Weeks 4 and 8, but not at Week 1. All three treatment groups' gloss scores improved during the study. Regarding tooth smoothness, the effects of the experimental toothpastes followed a broadly similar profile to the effects on tooth gloss. After four weeks' use, both experimental toothpastes were superior to the reference. After eight weeks' use, however, only the 2% alumina toothpaste approached significant superiority versus the reference

14 CFR Sec. 2-4 - Accounting period.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Accounting period. Sec. 2-4 Section 2-4... REGULATIONS UNIFORM SYSTEM OF ACCOUNTS AND REPORTS FOR LARGE CERTIFICATED AIR CARRIERS General Accounting Provisions Sec. 2-4 Accounting period. (a) The accounting year of each air carrier subject to this Uniform...

The physiological rhythms of subjects living on a day of abnormal length.

PubMed Central

Mills, J N; Minors, D S; Waterhouse, J M

1977-01-01

1. Fourteen subjects, singly or in groups, have been observed while living on a 21 hr day for 8 or 16 experimental 'days' and fifteen other subjects similarly on a 27 hr day. 2. Rhythmic components of body temperature and excretion of various urinary constituents were calculated. 3. On a 21 hr day, for most components and most subjects, two periods were present, one of 21 hr and one of around or somewhat over 24 hr. 4. On a 27 hr day two periods were less often present and a larger number of observed rhythms could be satisfactorily described by a single period, usually between 23 and 28 hr. 5. In subjects spending a second week on a 21 hr day the circadian component was no less prominent than during the first week. 6. When, after life on a 21 hr day, subjects were deprived of knowledge of time, there was evidence that the 21 hr component did not persist. 7. The results are interpreted as evidence of the continuing existance of an influence with a period of around 24 hr, simultaneously rhythmic influences resulting from the subjects' habits. On a 27 hr day there was sometimes evidence of entrainment, yielding an intermediate period. 8. An attempt is made to compare the relative potency of the exogenous and of the persistent circadian influences on the several variables. PMID:881648

A randomised trial to investigate the effects of acute consumption of a blackcurrant juice drink on markers of vascular reactivity and bioavailability of anthocyanins in human subjects.

PubMed

Jin, Y; Alimbetov, D; George, T; Gordon, M H; Lovegrove, J A

2011-07-01

To study the bioavailability of anthocyanins and the effects of a 20% blackcurrant juice drink on vascular reactivity, plasma antioxidant status and other cardiovascular disease risk markers. The study was a randomised, cross-over, double-blind, placebo-controlled acute meal study. Twenty healthy volunteers (11 females and 9 males) were recruited, and all subjects completed the study. Fasted volunteers consumed a 20% blackcurrant juice drink (250 ml) or a control drink following a low-flavonoid diet for the previous 72 h. Vascular reactivity was assessed at baseline and 120 min after juice consumption by laser Doppler imaging (LDI). Plasma and urine samples were collected periodically over an 8-h period for analysis, with a final urine sample collected at 24 h. The cross-over was performed after a 4-week washout. There were no significant effects of the 20% blackcurrant juice drink on acute measures of vascular reactivity, biomarkers of endothelial function or lipid risk factors. Consumption of the test juice caused increases in plasma vitamin C (P=0.006), and urinary anthocyanins (P<0.001). Delphinidin-3-rutinoside and cyanidin-3-rutinoside were the main anthocyanins excreted in urine with delphinidin-3-glucoside also detected. The yield of anthocyanins in urine was 0.021±0.003% of the dietary intake of delphinidin glycosides and 0.009±0.002% of the dietary intake of cyanidin glycosides. The juice consumption did not have a significant effect on vascular reactivity. Anthocyanins were present at low concentrations in the urine, and microbial metabolites of flavonoids were detected in plasma after juice consumption.

Salvage of infected craniotomy bone flaps with the wash-in, wash-out indwelling antibiotic irrigation system. Technical note and case series of 12 patients.

PubMed

Auguste, Kurtis I; McDermott, Michael W

2006-10-01

When complicated by infection, craniotomy bone flaps are commonly removed, discarded, and delayed cranioplasty is performed. This treatment paradigm is costly, carries the risks associated with additional surgery, and may cause cosmetic deformities. The authors present their experience with an indwelling antibiotic irrigation system used for the sterilization and salvage of infected bone flaps as an alternative to their removal and replacement. The authors retrospectively reviewed the medical records for 12 patients with bone flap infections following craniotomy who received treatment with the wash-in, wash-out indwelling antibiotic irrigation system. Infected flaps were removed and scrubbed with povidone-iodine solution and soaked in 1.5% hydrogen peroxide while the wound was debrided. The bone flaps were returned to the skull and the irrigation system was installed. Antibiotic medication was infused through the system for a mean of 5 days. Intravenous antibiotic therapy was continued for 2 weeks and oral antibiotics for 3 months postoperatively. Wound checks were performed at clinic follow-up visits, and there was a mean follow-up period of 13 months. Eleven of the 12 patients who had undergone placement of the bone flap irrigation system experienced complete resolution of the infection. In five patients there was involvement of the nasal sinus cavities, and in four there was a history of radiation treatment. In the one patient whose infection recurred, there was both involvement of the nasal sinuses and a history of extensive radiation treatment. Infected bone flaps can be salvaged, thus avoiding the cost, risk, and possible disfigurement associated with flap removal and delayed cranioplasty. Although prior radiation treatment and involvement of the nasal sinuses may interfere with wound healing and clearance of the infection, these factors should not preclude the use of irrigation with antibiotic agents for bone flap salvage.

Influence of Pacing by Periodic Auditory Stimuli on Movement Continuation: Comparison with Self-regulated Periodic Movement

PubMed Central

Ito, Masanori; Kado, Naoki; Suzuki, Toshiaki; Ando, Hiroshi

2013-01-01

[Purpose] The purpose of this study was to investigate the influence of external pacing with periodic auditory stimuli on the control of periodic movement. [Subjects and Methods] Eighteen healthy subjects performed self-paced, synchronization-continuation, and syncopation-continuation tapping. Inter-onset intervals were 1,000, 2,000 and 5,000 ms. The variability of inter-tap intervals was compared between the different pacing conditions and between self-paced tapping and each continuation phase. [Results] There were no significant differences in the mean and standard deviation of the inter-tap interval between pacing conditions. For the 1,000 and 5,000 ms tasks, there were significant differences in the mean inter-tap interval following auditory pacing compared with self-pacing. For the 2,000 ms syncopation condition and 5,000 ms task, there were significant differences from self-pacing in the standard deviation of the inter-tap interval following auditory pacing. [Conclusion] These results suggest that the accuracy of periodic movement with intervals of 1,000 and 5,000 ms can be improved by the use of auditory pacing. However, the consistency of periodic movement is mainly dependent on the inherent skill of the individual; thus, improvement of consistency based on pacing is unlikely. PMID:24259932

The washout effect during laundry on benzothiazole, benzotriazole, quinoline, and their derivatives in clothing textiles.

PubMed

Luongo, Giovanna; Avagyan, Rozanna; Hongyu, Ren; Östman, Conny

2016-02-01

In two previous papers, the authors have shown that benzothiazole, benzotriazole, quinoline, and several of their derivatives are widespread in clothing textile articles. A number of these compounds exhibit allergenic and irritating properties and, due to their octanol-water partition coefficient, are prone to be absorbed by the skin. Moreover, they are slightly soluble in water, which could make washing of clothes a route of emission into the environment. In the present study, the washout effect of benzothiazole, benzotriazole, quinoline, and some of their derivatives has been investigated. Twenty-seven textile samples were analyzed before, as well as after five and ten times of washing. The most abundant analyte was found to be benzothiazole, which was detected in 85 % of the samples with an average concentration of 0.53 μg/g (median 0.44 μg/g), followed by quinoline, detected in 81 % of the samples with an average concentration of 2.42 μg/g (median 0.21 μg/g). The average decrease in concentration for benzothiazoles was 50 % after ten times washing, while it was around 20 % for quinolines. The average emission to household wastewater of benzothiazoles and quinolines during one washing (5 kg of clothes made from polyester materials) was calculated to 0.5 and 0.24 g, respectively. These results strongly indicate that laundering of clothing textiles can be an important source of release of these compounds to household wastewater and in the end to aquatic environments. It also demonstrates a potential source of human exposure to these chemicals since considerable amounts of the compounds remain in the clothes even after ten times of washing.

Hepatic Hemangiomas: Factors Associated with Pseudo Washout Sign on Gd-EOB-DTPA-enhanced MR Imaging.

PubMed

Tateyama, Akihiro; Fukukura, Yoshihiko; Takumi, Koji; Shindo, Toshikazu; Kumagae, Yuichi; Nakamura, Fumihiko

2016-01-01

Our study aim was to clarify the characteristics of hemangiomas with pseudo washout sign (PWS) by comparing their features with those of hemangiomas without PWS on gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) imaging. We evaluated the features of hemangiomas on Gd-EOB-DTPA-enhanced MR imaging of 70 hepatic hemangiomas in 31 patients, investigating the presence of peripheral or central nodular enhancement, diffuse enhancement, and arterioportal shunt during the arterial phase, fill-in enhancement during the portal venous phase, and PWS, which is low signal intensity during the late phase. We visually assessed the intensity of contrast enhancement of the lesion during the arterial, portal venous, late, and hepatobiliary phases using a 4-grade scale and used the Fisher exact and Mann-Whitney U tests to compare hemangiomas with and without PWS. We observed PWS in 33 (47%) of 70 hemangiomas, which were significantly smaller than the hemangiomas without PWS (17.4 mm ± 20.3 versus 30.1 mm ± 28.5; P = 0.005); more frequent diffuse enhancement in hemangiomas with PWS than those without (21.2% versus 2.7%; P = 0.026); and no significant differences in nodular enhancement (P = 0.231), arterioportal shunt (P = 0.403), or fill-in enhancement (P = 0.357) between hemangiomas with and without PWS. Visually determined grades of tumor contrast enhancement were significantly lower in hemangiomas with PWS during the portal venous (P = 0.007) and late (P < 0.001) phases. Small hemangiomas tend to decrease in signal intensity during the portal venous phase and show PWS during the late phase.

The Endotoxemia Marker Lipopolysaccharide-Binding Protein is Reduced in Overweight-Obese Subjects Consuming Pomegranate Extract by Modulating the Gut Microbiota: A Randomized Clinical Trial.

PubMed

González-Sarrías, Antonio; Romo-Vaquero, María; García-Villalba, Rocío; Cortés-Martín, Adrián; Selma, María Victoria; Espín, Juan Carlos

2018-06-01

Gut microbiota dysbiosis, intestinal barrier failure, obesity, metabolic endotoxemia, and pro-inflammatory status promote cardiovascular risk. However, the modulation of the gut microbiome to prevent endotoxemia in obesity has been scarcely studied. We investigated the association between gut microbiota modulation and plasma lipopolysaccharide-binding protein (LBP), a surrogate marker of endotoxemia, in overweight-obese individuals. In a randomized trial, 49 overweight-obese subjects (body mass index> 27 kg m -2 ) with mild hypelipidemia daily consumed, in a cross-over fashion, two doses (D1 and D2, lasting 3 weeks each) of pomegranate extract (PE) or placebo alternating with 3 weeks of wash-out periods. A significant decrease (p < 0.05) of plasma LBP and a marginal decrease (p = 0.054) of high-sensitivity C-reactive protein were observed, but only after PE-D2 administration (656 mg phenolics). 16S rDNA sequencing analyses revealed the increase of microorganisms important for maintaining normal balance of gut microbiota and gut barrier function, particularly Bacteroides, Faecalibacterium, Butyricicoccus, Odoribacter, and Butyricimonas. PE-D2 also decreased pro-inflammatory microorganisms including Parvimonas, Methanobrevibacter, and Methanosphaera. Remarkably, plasma LBP reduction was significantly associated (p < 0.05) with both Faecalibacterium and Odoribacter increase and Parvimonas decrease. Consumption of PE decreased endotoxemia in overweight-obese individuals by reshaping the gut microbiota, mainly through the modulation of Faecalibacterium, Odoribacter, and Parvimonas. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pulmonary performance of elderly normal subjects and subjects with chronic obstructive pulmonary disease exposed to 0. 3 ppm nitrogen dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morrow, P.E.; Utell, M.J.; Bauer, M.A.

1992-02-01

Symptoms and changes in pulmonary function of subjects with chronic obstructive pulmonary disease (COPD) and elderly normal subjects, induced by a 4-h exposure to 0.3 ppm NO2, were investigated using a double-blind, crossover design with purified air. The 5-day experimental protocol required approximately 2 wk with at least a 5-day separation between randomized 4-h exposures to either NO2 or air which included several periods of exercise. Over a 2-yr period, COPD subjects, all with a history of smoking, consisting of 13 men and 7 women (mean age of 60.0 yr) and 20 elderly normal subjects of comparable age and sexmore » were evaluated. During intermittent light exercise, COPD subjects demonstrated progressive decrements in FVC and FEV1 compared with baseline with 0.3 ppm NO2, but not with air. Differences in percent changes from baseline data (air-NO2) showed an equivocal reduction in FVC by repeated measures of analysis of variance and cross-over t tests (p less than 0.10). Subgroup analyses suggested that responsiveness to NO2 decreased with severity of COPD; in elderly normal subjects, NO2-induced reduction in FEV1 was greater among smokers than never-smokers. A comparison of COPD and elderly normal subjects also revealed distinctions in NO2-induced responsiveness.« less

A comparison of salicylic acid levels in normal subjects after rectal versus oral dosing.

PubMed

Maalouf, Roger; Mosley, Mark; James Kallail, K; Kramer, Karen M; Kumar, Gaurav

2009-02-01

The common practice is to use 162 mg of aspirin orally in the emergency department (ED) for patients presenting with myocardial infarction. If the patient cannot take aspirin orally in the authors' facility, then 600 mg of aspirin is given rectally. However, no strong evidence exists as to whether the oral and rectal doses provide equivalent risk protection. The authors hypothesized that the salicylic acid levels for orally and rectally administered aspirin will not be similar, because of the different dosages used and the different routes of administration. The study sample consisted of healthy, nonpregnant, adult volunteers without active illness, who did not take any medication regularly. Each subject served as his or her own control to account for any confounding factors. The study was conducted on 2 days, separated by a 1-week washout period. On the first day, 162 mg of oral aspirin was chewed and swallowed. Salicylic acid levels were obtained at baseline (i.e., before taking the aspirin) and then 30, 60, and 90 minutes after dosing. The 600-mg aspirin suppository was self-administered 1 week later with a sample for laboratory measures again drawn at baseline and then 30, 60, and 90 minutes after dosing. Twenty-four subjects completed the study. The rectal suppository provided significantly more salicylic acid into the blood than the oral tablets over 90 minutes (p < 0.001). No statistical difference was noted between oral and rectal administration from baseline to 30 minutes (p > 0.05). However, mean salicylic acid levels from the rectal suppository were statistically higher than from the oral tablets from 30 to 60 minutes (p < 0.001) and from 60 to 90 minutes (p = 0.002). More than 60% of the subjects had an increasing salicylic acid level response over time to the rectal suppository. The salicylic acid level response to the oral administration was more evenly divided between those subjects whose salicylic acid levels peaked quickly and then fell or held

Subjective age and personality development: a 10-year study.

PubMed

Stephan, Yannick; Sutin, Angelina R; Terracciano, Antonio

2015-04-01

Personality theory and research typically focus on chronological age as a key indicator of personality development. This study examines whether the subjective experience of age is an alternative marker of the biomedical and psychosocial factors that contribute to individual differences in personality development. The present study uses data from the Midlife in the United States longitudinal survey (N = 3,617) to examine how subjective age is associated with stability and change in personality and the dynamic associations between subjective age and personality traits over a 10-year period. Regression analyses indicated that a younger subjective age at baseline was associated with increases in Openness, Conscientiousness, and Agreeableness; correlated changes were also found. The rank-order stability of Extraversion and Openness and overall profile consistency were higher among those with a younger subjective age at baseline and were also associated with the rate of subjective aging over time. The present study reveals that beyond chronological age, the age an individual feels is related to changes in characteristic ways of thinking, feeling, and behaving over time. © 2014 Wiley Periodicals, Inc.

Impotence evaluated by the use of prostaglandin E1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, T.I.; Yang, C.R.; Wang, S.J.

1989-06-01

We screened 80 patients at our hospital for the differential diagnosis of impotence using intracavernous injection of prostaglandin E1 (20 micrograms). The rate of positive response was 78.8 per cent (63 patients). Neither systemic reactions nor priapism occurred. However, a considerable incidence (23.8 per cent, 19 of 80 patients) of tolerable injection pain was encountered. The 133-xenon penile washout study was conducted routinely in impotent men for hemodynamic evaluation of penile vascularity. In 80 patients a positive correlation between the response of intracavernous prostaglandin E1 injection and the result of the washout study was found (r equals 0.381, p lessmore » than 0.0002). We selected 14 subjects randomly to receive additional intravenous infusions of prostaglandin E1 (6 ampules, 120 micrograms total) for 3 days, after which another 133-xenon washout study was done. The washout studies before and after intravenous prostaglandin E1 infusion were compared, and 10 patients (71.4 per cent) appeared to obtain improvement in half-time clearance and penile blood flow. However, only 3 patients noticed improvement subjectively. We suggest that prostaglandin E1 could be a desirable alternative for the diagnosis and treatment of impotence.« less

The Effects of Valbenazine in Participants with Tardive Dyskinesia: Results of the 1-Year KINECT 3 Extension Study.

PubMed

Factor, Stewart A; Remington, Gary; Comella, Cynthia L; Correll, Christoph U; Burke, Joshua; Jimenez, Roland; Liang, Grace S; O'Brien, Christopher F

Valbenazine, a highly selective vesicular monoamine transporter 2 inhibitor, is approved for the treatment of tardive dyskinesia. This is the first report of long-term effects in adults with tardive dyskinesia. Participants with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or a mood disorder who completed the 6-week, double-blind, placebo-controlled period of KINECT 3 were eligible to enter the 42-week valbenazine extension (VE) period and subsequent 4-week washout period. The extension phase was conducted from December 16, 2014, to August 3, 2016. Participants who received placebo and entered the VE period were re-randomized 1:1 to valbenazine 80 or 40 mg while others continued valbenazine at the KINECT 3 dose. Safety assessments included treatment-emergent adverse events (TEAEs) and scales for suicidal ideation/behavior, treatment-emergent akathisia or parkinsonism, and psychiatric symptoms. Efficacy assessments included the Abnormal Involuntary Movement Scale (AIMS) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD). 198 participants entered the VE period, 124 (62.6%) completed treatment (week 48), and 121 (61.1%) completed the follow-up visit after washout (week 52). During the VE period, 69.2% of participants had ≥ 1 TEAE, 14.6% had a serious TEAE, and 15.7% discontinued due to a TEAE. During washout, 13.1% of participants experienced a TEAE. No apparent risk for suicidal ideation or behavior was found. Long-term valbenazine treatment did not appear to induce or worsen akathisia or parkinsonism. Participants generally remained psychiatrically stable during the study. AIMS and CGI-TD measures indicated sustained tardive dyskinesia improvement, with scores returning toward baseline after 4 weeks of valbenazine washout. The long-term safety and tolerability of valbenazine were generally favorable, and maintenance of treatment effect was apparent with both doses during this long-term study. ClinicalTrials.gov identifier: NCT

Improvement in antithrombogenicity in a centrifugal pump with self wash-out structure for long-term use.

PubMed

Wakisaka, Y; Taenaka, Y; Tatsumi, E; Araki, K; Masuzawa, T; Nakatani, T; Baba, Y; Anai, H; Eya, K; Toda, K

1995-01-01

Antithrombogenicity in the initial (NCVC-1) centrifugal pump (CP) developed at our institute is provided by a central balancing hole in an impeller that promotes self wash-out blood flow (Sf) around the impeller. The current CP (NCVC-2) was ameliorated to obtain better antithrombogenicity, where the balancing hole diameter was widened to improve Sf velocity (Vsf), and the edge of a thrust bearing (TB) was rounded to minimize flow separation. Effects of the modifications were assessed in in vitro and in vivo studies. The Vsf of the NCVC-1 and the NCVC-2 evaluated by Doppler velocimeter were 12.8 and 22.1 cm/sec, respectively. Flow around the TB visualized by a light cutting method confirmed less flow stagnation in the NCVC-2. In vivo antithrombogenicity of the CPs was investigated in three goats. A pulsatile VAD (P-VAD) was installed paracorporeally between the left atrium and the aorta. After 3 weeks, the P-VAD was exchanged for the NCVC-2 and the NCVC-1 in sequence. Each CP was driven for 1 week and disassembled. No anticoagulation was used, except for heparin injection at pump exchange. Thrombus at the TB was found in the two NCVC-1s, and two little thrombi were on the impeller of another NCVC-1, whereas a thrombus smaller than 1 mm3 at the TB was noted in one NCVC-2. These results indicate that the NCVC-2 has better antithrombogenicity and Sf around the impeller and the TB.

Fluoridated elastomers: effect on the microbiology of plaque.

PubMed

Benson, Philip E; Douglas, C W Ian; Martin, Michael V

2004-09-01

The objective of this study was to investigate the effect of fluoridated elastomeric ligatures on the microbiology of local dental plaque in vivo. This randomized, prospective, longitudinal, clinical trial had a split-mouth crossover design. The subjects were 30 patients at the beginning of their treatment with fixed orthodontic appliances in the orthodontic departments of the Liverpool and the Sheffield dental hospitals in the United Kingdom. The study consisted of 2 experimental periods of 6 weeks with a washout period between. Fluoridated elastomers were randomly allocated at the first visit to be placed around brackets on tooth numbers 12, 11, 33 or 22, 21, 43. Nonfluoridated elastomers were placed on the contralateral teeth. Standard nonantibacterial fluoridated toothpaste and mouthwash were supplied. After 6 weeks (visit 2), the elastomers were removed, placed in transport media, and plated on agar within 2 hours. Nonfluoridated elastomers were placed on all brackets for 1 visit to allow for a washout period. At visit 3, fluoridated elastomers were placed on the teeth contralateral to those that received them at visit 1. At visit 4, the procedures at visit 2 were repeated. Samples were collected on visits 2 and 4. A logistic regression was performed, with the presence or absence of streptococcal or anaerobic growth as the dependent variable. A mixed-effects analysis of variance was carried out with the percentage of streptococcal or anaerobic bacterial count as the dependent variable. The only significant independent variables were the subject variable (P =<.001) for the percentage of streptococcal and anaerobic bacterial count and the visit variable for the percentage of streptococcal count (P =<.001). The use of fluoridated or nonfluoridated elastomers was not significant for percentage of either streptococcal (P =.288) or anaerobic count (P =.230). Fluoridated elastomers are not effective at reducing local streptococcal or anaerobic bacterial growth after

Effect of alcohol consumption on the liver detoxication capacity as measured by [13C]methacetin- and [methyl-13C]methionine-breath tests.

PubMed

Wutzke, Klaus D; Forberger, Anke; Wigger, Marianne

2008-06-01

The aim of this study was to investigate the hepatic microsomal and mitochondrial functions by using the 13CO2-breath test in healthy subjects either before or after the consumption of red wine. Fourteen adults received [13C]methacetin and [methyl-13C]methionine together with a standardised dinner. Expired air samples were taken over 6 h. After a wash-out period, the subjects consumed 0.4 ml ethanol/kg/day together with dinner over a 10-day period. Thereafter, 13C-tracer administration was repeated under identical conditions. The 13CO2-enrichments were measured by isotope ratio mass spectrometry. The mean cumulative percentage 13C-dose recovery (CPDR) after administration of [13C]methacetin and [methyl-13C]methionine either without or with red wine consumption amounted to 38.2+/-6.3 vs. 36.3+/-6.7% (p=0.363) and 9.5+/-3.3 vs. 8.8+/-2.5% (p=0.47), respectively. Moderate alcohol consumption does not induce significant short-term changes of the microsomal and the mitochondrial functions of the human liver in healthy subjects.

Subjective Responses to Oral Tobacco Products: Scale Validation

PubMed Central

2013-01-01

Introduction: Several noncombusted oral tobacco products have been introduced that are primarily marketed to cigarette smokers. An important component of evaluating these products involves assessment of subjective responses to the product. To date, few studies have been undertaken to examine the validity of subjective response questionnaires for oral tobacco products. The goal of this study is to examine the extent subjective responses to a product are related to product preference and extent of product use. Methods: Data from a study examining oral tobacco product preference were used. Smokers were asked to sample a variety of oral tobacco products that differed in formulation (snus versus dissolvables) and dose of nicotine. At the end of the sampling period, subjects were asked to choose the product that they would use to completely substitute for cigarettes for the next 2 weeks. During the sampling period, subjects completed a Product Evaluation Scale (PES) that describes subjective responses to the product. During the treatment phase, they kept record of amount of product use. Results: Subjective responses to the product on the PES were related to product choice and to some extent, the amount of product use. Product choice was associated with different characteristics of the product and smoker needs. Conclusion: The PES may be a useful tool for the evaluation or oral tobacco products. PMID:23239843

Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients.

PubMed

Moreno-Indias, Isabel; Sánchez-Alcoholado, Lidia; Pérez-Martínez, Pablo; Andrés-Lacueva, Cristina; Cardona, Fernando; Tinahones, Francisco; Queipo-Ortuño, María Isabel

2016-04-01

This study evaluated the possible prebiotic effect of a moderate intake of red wine polyphenols on the modulation of the gut microbiota composition and the improvement in the risk factors for the metabolic syndrome in obese patients. Ten metabolic syndrome patients and ten healthy subjects were included in a randomized, crossover, controlled intervention study. After a washout period, the subjects consumed red wine and de-alcoholized red wine over a 30 day period for each. The dominant bacterial composition did not differ significantly between the study groups after the two red wine intake periods. In the metabolic syndrome patients, red wine polyphenols significantly increased the number of fecal bifidobacteria and Lactobacillus (intestinal barrier protectors) and butyrate-producing bacteria (Faecalibacterium prausnitzii and Roseburia) at the expense of less desirable groups of bacteria such as LPS producers (Escherichia coli and Enterobacter cloacae). The changes in gut microbiota in these patients could be responsible for the improvement in the metabolic syndrome markers. Modulation of the gut microbiota by using red wine could be an effective strategy for managing metabolic diseases associated with obesity.

Survival probability of a truncated radial oscillator subject to periodic kicks

NASA Astrophysics Data System (ADS)

Tanabe, Seiichi; Watanabe, Shinichi; Saif, Farhan; Matsuzawa, Michio

2002-03-01

Classical and quantum survival probabilities are compared for a truncated radial oscillator undergoing impulsive interactions with periodic laser pulses represented here as kicks. The system is truncated in the sense that the harmonic potential is made valid only within a finite range; the rest of the space is treated as a perfect absorber. Exploring extended values of the parameters of this model [Phys. Rev. A 63, 052721 (2001)], we supplement discussions on classical and quantum features near resonances. The classical system proves to be quasi-integrable and preserves phase-space area despite the momentum transfered by the kicks, exhibiting simple yet rich phase-space features. A geometrical argument reveals quantum-classical correspondence in the locations of minima in the paired survival probabilities while the ``ionization'' rates differ due to quantum tunneling.

Within- and between- subject variability in methadone pharmacokinetics and pharmacodynamics in methadone maintenance subjects

PubMed Central

Hanna, Julia; Foster, David JR; Salter, Amy; Somogyi, Andrew A; White, Jason M; Bochner, Felix

2005-01-01

Aims To investigate within- and between-subject variability of the pharmacodynamics and pharmacokinetics of (R)- and (S)-methadone in methadone maintenance subjects at steady-state. Methods Six non-holder subjects were studied on three occasions at 7–16 day intervals; doses (20–170 mg/day) remained unchanged. Blood samples and pharmacodynamic data were collected 10–12 times over a 24-h inter-dosing interval. All pharmacodynamic data were expressed as the area under the end-point versus time curve. Using analyses of variance with mixed effects, best estimates were made of the ratio of between- to within-subject variation, with corresponding 95% confidence intervals (CI) for within-subject variation at the average value. Results Subjects were relatively consistent between occasions, whereas there was much greater between-subject variability (P < 0.02) for all measures. Estimates of the ratio of between- to within-subject variation ranged from 2.2–12.8 for pharmacodynamic measures, and 1.3–7.9 for pharmacokinetic parameters. For pain, total mood disturbance, withdrawal, pupil size and respiration rate, 95% CI for within-subject measures ranged ≤2-fold, while this was greater for subjective direct opioid effects (4.2-fold). For CL/F of the active (R)-methadone, the variance ratio was 4.9 (P < 0.0003), with 95% CI for within-subject measures ranging ≤2-fold. (S)-methadone CL/F demonstrated greater within-subject variability (3.4-fold), possibly contributing to a smaller (2.7; P < 0.0003) ratio of between- to within-subject variance. Conclusions Non-holder methadone maintenance treatment participants appear to respond consistently with respect to pharmacokinetics and pharmacodynamics over a 1–2 month period. Such knowledge may help prescribers to determine whether alternative dosing regimens or treatments might be more appropriate in this population. PMID:16187972

Early detection of cystic fibrosis lung disease: multiple‐breath washout versus raised volume tests

PubMed Central

Lum, Sooky; Gustafsson, Per; Ljungberg, Henrik; Hülskamp, Georg; Bush, Andrew; Carr, Siobhán B; Castle, Rosemary; Hoo, Ah‐fong; Price, John; Ranganathan, Sarath; Stroobant, John; Wade, Angie; Wallis, Colin; Wyatt, Hilary; Stocks, Janet

2007-01-01

Background Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from the multiple‐breath inert gas washout (MBW) technique, has been shown to detect abnormal lung function more readily than spirometry in preschool children with cystic fibrosis, but whether this holds true during infancy is unknown. Objectives To compare the extent to which parameters derived from the MBW and the raised lung volume rapid thoraco–abdominal compression (RVRTC) techniques identify diminished airway function in infants with cystic fibrosis when compared with healthy controls. Methods Measurements were performed during quiet sleep, with the tidal breathing MBW technique being performed before the forced expiratory manoeuvres. Results Measurements were obtained in 39 infants with cystic fibrosis (mean (SD) age 41.4 (22.0) weeks) and 21 controls (37.0 (15.1) weeks). Infants with cystic fibrosis had a significantly higher respiratory rate (38 (10) vs 32 (5) bpm) and LCI (8.4 (1.5) vs 7.2 (0.3)), and significantly lower values for all forced expiratory flow‐volume parameters compared with controls. Girls with cystic fibrosis had significantly lower forced expiratory volume (FEV0.5 and FEF25–75 ) than boys (mean (95% CI girls–boys): –1.2 (–2.1 to −0.3) for FEV0.5 Z score; FEF25–75: –1.2 (–2.2 to −0.15)). When using both the MBW and RVRTC techniques, abnormalities were detected in 72% of the infants with cystic fibrosis, with abnormalities detected in 41% using both techniques and a further 15% by each of the two tests performed. Conclusions These findings support the view that inflammatory and/or structural changes in the airways of children with cystic fibrosis start early in life, and have important implications regarding early detection and interventions. Monitoring of early lung disease and functional status in infants and young children with cystic fibrosis may be enhanced by using both MBW and the RVRTC. PMID:17121870

Lack of a meaningful effect of anacetrapib on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects

PubMed Central

Krishna, Rajesh; Stypinski, Daria; Ali, Melissa; Garg, Amit; Cote, Josee; Maes, Andrea; DeGroot, Bruce; Liu, Yang; Li, Susie; Connolly, Sandra M; Wagner, John A; Stoch, S Aubrey

2012-01-01

AIM Anacetrapib is currently being developed for the treatment of dyslipidaemia. Since warfarin, an anticoagulant with a narrow therapeutic index, is expected to be commonly prescribed in this population, a drug interaction study was conducted. METHODS In a randomized, open-label, two-period fixed-sequence design, 12 healthy male subjects received two different treatments (treatment A followed by treatment B). In treatment A, a single oral dose of 30 mg warfarin (3 × 10 mg CoumadinTM) was administered on day 1. After a washout interval, subjects began treatment B, where they were given daily 100 mg doses of anacetrapib (1 × 100 mg) beginning on day −14 and continuing through day 7, with concomitant administration of 30 mg warfarin (3 × 10 mg) on day 1. All anacetrapib and warfarin doses were administered with a standard low fat breakfast. After warfarin concentrations and prothrombin time were measured, standard pharmacokinetic, pharmacodynamic and statistical (linear mixed effects model) analyses were applied. RESULTS Anacetrapib was generally well tolerated when co-administered with warfarin in the healthy males in this study. The geometric mean ratios (GMRs) for warfarin + anacetrapib : warfarin alone and 90% confidence interval (CIs) for warfarin AUC(0–∞) were 0.94 (0.90, 0.97) for the R(+) warfarin enantiomer and 0.93 (0.87, 0.98) for the S(−) warfarin enantiomer, both being contained in the interval (0.80, 1.25), supporting the primary hypothesis of the study. The GMRs warfarin + anacetrapib : warfarin alone and 90% CIs for the statistical comparison of warfarin Cmax were 1.01 (0.97, 1.05) for both the R(+) warfarin and the S(−) warfarin enantiomers, and were also contained in the interval (0.80, 1.25). The GMR (warfarin + anacetrapib : warfarin alone) and 90% CI for the statistical comparison of INR AUC(0–168 h) was 0.93 (0.89, 0.96). CONCLUSION The single dose pharmacokinetics and pharmacodynamics of orally administered warfarin were not

Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk.

PubMed

Jianqin, Sun; Leiming, Xu; Lu, Xia; Yelland, Gregory W; Ni, Jiayi; Clarke, Andrew J

2016-04-02

Cows' milk generally contains two types of β-casein, A1 and A2 types. Digestion of A1 type can yield the peptide β-casomorphin-7, which is implicated in adverse gastrointestinal effects of milk consumption, some of which resemble those in lactose intolerance. This study aimed to compare the effects of milk containing A1 β-casein with those of milk containing only A2 β-casein on inflammation, symptoms of post-dairy digestive discomfort (PD3), and cognitive processing in subjects with self-reported lactose intolerance. Forty-five Han Chinese subjects participated in this double-blind, randomized, 2 × 2 crossover trial and consumed milk containing both β-casein types or milk containing only A2 β-casein. Each treatment period was 14 days with a 14-day washout period at baseline and between treatment periods. Outcomes included PD3, gastrointestinal function (measured by smart pill), Subtle Cognitive Impairment Test (SCIT), serum/fecal laboratory biomarkers, and adverse events. Compared with milk containing only A2 β-casein, the consumption of milk containing both β-casein types was associated with significantly greater PD3 symptoms; higher concentrations of inflammation-related biomarkers and β-casomorphin-7; longer gastrointestinal transit times and lower levels of short-chain fatty acids; and increased response time and error rate on the SCIT. Consumption of milk containing both β-casein types was associated with worsening of PD3 symptoms relative to baseline in lactose tolerant and lactose intolerant subjects. Consumption of milk containing only A2 β-casein did not aggravate PD3 symptoms relative to baseline (i.e., after washout of dairy products) in lactose tolerant and intolerant subjects. Consumption of milk containing A1 β-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 β-casein attenuated these effects

Diminution of context association memory structure in subjects with subjective cognitive decline.

PubMed

Fan, Ling-Yun; Lai, Ya-Mei; Chen, Ta-Fu; Hsu, Yung-Chin; Chen, Pin-Yu; Huang, Kuo-Zhou; Cheng, Ting-Wen; Tseng, Wen-Yi Isaac; Hua, Mau-Sun; Chen, Ya-Fang; Chiu, Ming-Jang

2018-06-01

Alzheimer's disease (AD) progresses insidiously from the preclinical stage to dementia. While people with subjective cognitive decline (SCD) have normal cognitive performance, some may be in the preclinical stage of AD. Neurofibrillary tangles appear first in the transentorhinal cortex, followed by the entorhinal cortex in the clinically silent stage of AD. We expected the earliest changes in subjects with SCD to occur in medial temporal subfields other than the hippocampal proper. These selective structural changes would affect specific memory subcomponents. We used the Family Picture subtest of the Wechsler Memory Scale-III, which was modified to separately compute character, activity, and location subscores for episodic memory subcomponents. We recruited 43 subjects with SCD, 44 subjects with amnesic mild cognitive impairment, and 34 normal controls. MRI was used to assess cortical thickness, subcortical gray matter volume, and fractional anisotropy. The results demonstrated that SCD subjects showed significant cortical atrophy in their bilateral parahippocampus and perirhinal and the left entorhinal cortices but not in their hippocampal regions. SCD subjects also exhibited significantly decreased mean fractional anisotropy in their bilateral uncinate fasciculi. The diminution of cortical thickness over the mesial temporal subfields corresponded to brain areas with early tangle deposition, and early degradation of the uncinate fasciculus was in accordance with the retrogenesis hypothesis. The parahippocampus and perirhinal cortex contribute mainly to context association memory while the entorhinal cortex, along with the uncinate fasciculus, contributes to content-related contextual memory. We proposed that context association and related memory structures are vulnerable in the SCD stage. © 2018 Wiley Periodicals, Inc.

Cabin Safety Subject Index,

DTIC Science & Technology

1984-01-01

1949 CABIN SAFETY SUBJECT XNDEX(U) FEDERAL AVIATION /~D-AiS 4e9 ADMINISTRATION WASHINGTON DC OFFICE OF RYIRTION MEDICINE D N POLLARD ET AL. JAN 84...City, Oklahoma 73125 13. Type of Report and Period Covered 12. Sponsoring Agency Name and AddressOffice of Aviation Medicine & Office of Flight...Regulations numbers, Air Carrier Operations Bulletin numbers, Advisory Circular numbers, and Office of Aviation Medicine report numbers. U

Effects of Food on the Pharmacokinetics of Omega-3-Carboxylic Acids in Healthy Japanese Male Subjects: A Phase I, Randomized, Open-label, Three-period, Crossover Trial.

PubMed

Shimada, Hitoshi; Nilsson, Catarina; Noda, Yoshinori; Kim, Hyosung; Lundström, Torbjörn; Yajima, Toshitaka

2017-09-01

Omega-3-carboxylic acids (OM3-CA) contain omega-3 free fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as carboxylic acids. Food intake is known to affect the bioavailability of ethyl ester fatty acid formulations. We conducted a phase I study to investigate the effects of the timing of OM3-CA administration relative to food intake on the pharmacokinetics of EPA and DHA. In this randomized, open-label, three-period crossover study, Japanese healthy male subjects were administered 4×1 g OM3-CA capsules with continued fasting, before a meal, or after a meal. All subjects fasted for ≥10 h prior to drug/meal administration. The primary objective was to examine the effect of meal timing on the pharmacokinetics of EPA and DHA after OM3-CA administration. The secondary objectives were to examine the safety and tolerability of OM3-CA. A total of 42 Japanese subjects was enrolled in the study. The baseline-adjusted maximum concentration and area under the concentration-time curve from 0 to 72 h for EPA, DHA, and EPA +DHA were lower in the fasting and before meal conditions than in the after meal condition. The maximum total EPA, total DHA, and total EPA+DHA concentrations were reached later when administered in fasting conditions than in fed conditions, indicating slower absorption in fasting conditions. Diarrhea was reported by five, six, and no subjects in the fasting, before meal, and after meal conditions, respectively. The timing of OM3-CA administration relative to food intake influences the systemic bioavailability of EPA and DHA in healthy Japanese male subjects. NCT02372344.

Critical fluctuations near the pitchfork bifurcations of period-doubling maps

NASA Astrophysics Data System (ADS)

Noble, Andrew; Karimeddiny, Saba; Hastings, Alan; Machta, Jonathan

2015-03-01

Period-doubling maps, such as the logistic map, have been a subject of intense study in both physics and biology. The period-doubling route to chaos proceeds through a sequence of supercritical pitchfork bifurcations. Here, motivated by applications to population ecology, we investigate the asymptotic behavior of period-doubling bifurcations subject to environmental or demographic noise. We demonstrate, analytically, that fluctuations in the vicinity of each noisy pitchfork bifurcation are described by finite-size mean-field theory. Our results establish an exact correspondence between the bifurcations of far-from-equilibrium systems and the mean-field critical phenomena of equilibrium systems. This material is based upon work supported by the National Science Foundation under INSPIRE Grant No. 1344187.

New method to calculate the N2 evolution from mixed venous blood during the N2 washout.

PubMed

Han, D; Jeng, D R; Cruz, J C; Flores, X F; Mallea, J M

2001-08-01

To model the normalized phase III slope (Sn) from N2 expirograms of the multibreath N2 washout is a challenge to researchers. Experimental measurements show that Sn increases with the number of breaths. Previously, we predicted Sn by setting the concentration (atm) of mixed venous blood (Fbi,N2) to a constant value of 0.3 after the fifth breath to calculate the amount of N2 transferred from the blood to the alveoli. As a consequence, the predicted curve of the Sn values showed a maximum before the quasi-steady state was reached. In this paper, we present a way of calculating the amount of N2 transferred from the blood to the alveoli by setting Fbi,N2 in the following way: In the first six breaths Fbi,N2 is kept constant at the initial value of 0.8 because circulation time needs at least 30 s to alter it. Thereafter, a single exponential function with respect the number of breaths is used: Fbi = 0.8 exp[0.112(6-n)], in which n is the breath number. The predicted Sn values were compared with experimental data from the literature. The assumption of an exponential decay in the N2 evolved from mixed venous blood is important in determining the shape of the Sn curve but new experimental data are needed to determine the validity of the model. We concluded that this new approach to calculate the N2 evolution from the blood is more meaningful physiologically.

Effect of muscadine grape seed supplementation on vascular function in subjects with or at risk for cardiovascular disease: a randomized crossover trial.

PubMed

Mellen, Philip B; Daniel, Kurt R; Brosnihan, K Bridget; Hansen, Kim J; Herrington, David M

2010-10-01

Muscadine grape seeds have high concentrations of polyphenolic compounds with antioxidant and other properties that would be expected to have favorable effects on endothelial function. To evaluate the effect of muscadine grape seed supplementation on endothelial function and cardiovascular risk factors in subjects with increased cardiovascular risk. In a randomized, double-blind, placebo-controlled crossover trial, 50 adults with coronary disease or ≥1 cardiac risk factor received muscadine grape seed supplementation (1300 mg daily) and placebo for 4 weeks each, with a 4-week washout. Resting brachial diameter and brachial flow-mediated dilation (FMD) and biomarkers of inflammation, lipid peroxidation, and antioxidant capacity were determined at the beginning and end of each period and compared in mixed linear models. There was no evidence of improved FMD (% change) with muscadine grape seed (muscadine grape seed: pre 5.2% ± 0.3%, post 4.6% ± 0.3%, p = 0.06; placebo: pre 5.3% ± 0.4%, post 5.2% ± 0.4%, p = 0.82; p for muscadine grape seed vs. placebo = 0.25). However, there was a significant increase in baseline diameter (mm) with muscadine grape seed supplementation (muscadine grape seed: pre 4.05 ± 0.09, post 4.23 ± 0.10, p = 0.002; placebo: pre 4.12 ± 0.11, post 4.12 ± 0.10, p = 0.93; p for muscadine grape seed vs. placebo = 0.026). All other biomarkers were not significantly altered by muscadine grape seed supplementation. Four weeks of muscadine grape seed supplementation in subjects with increased cardiovascular risk did not produce a statistically significant increase in brachial flow-mediated vasodilation or a significant change in other biomarkers of inflammation, lipid peroxidation, or antioxidant capacity. However, the muscadine grape seed supplement did result in a significant increase in resting brachial diameter. The clinical significance of the effect on resting diameter is not yet established. More research is warranted to fully

Conduction velocity and refractory period of single motor nerve fibres in antecedent poliomyelitis.

PubMed Central

Borg, K; Borg, J

1987-01-01

The axonal conduction velocity and the axonal refractory period were determined using electromyographic techniques for 60 single motor units in 11 patients with antecedent poliomyelitis. The results were compared with previous observations in healthy subjects as well as subjects with motor neuron disease. In antecedent poliomyelitis there was a reduced proportion of nerve fibres with low conduction velocity as compared with the findings in healthy subjects. The mean value of the axonal conduction velocities in antecedent poliomyelitis (42.4 +/- 3.7 m/s, M +/- SD) was significantly higher (p less than 0.01) while in motor neuron disease the corresponding value (35.2 +/- 7.8 m/s) was significantly lower (p less than 0.005) than in healthy subjects (39.8 +/- 4.9 m/s). In antecedent poliomyelitis the conduction velocity and refractory period were related as in healthy subjects while abnormally long refractory periods were observed in motor neuron disease. Images PMID:3585356

Chronic dietary exposure to branched chain amino acids impairs glucose disposal in vegans but not in omnivores.

PubMed

Gojda, J; Rossmeislová, L; Straková, R; Tůmová, J; Elkalaf, M; Jaček, M; Tůma, P; Potočková, J; Krauzová, E; Waldauf, P; Trnka, J; Štich, V; Anděl, M

2017-05-01

Branched chain amino acids (BCAA) are among nutrients strongly linked with insulin sensitivity (IS) measures. We investigated the effects of a chronic increase of BCAA intake on IS in two groups of healthy subjects differing in their basal consumption of BCAA, that is, vegans and omnivores. Eight vegans and eight matched omnivores (five men and three women in each group) received 15 g (women) or 20 g (men) of BCAA daily for 3 months. Anthropometry, blood analyses, glucose clamp, arginine test, subcutaneous abdominal adipose tissue (AT) and skeletal muscle (SM) biopsies (mRNA levels of selected metabolic markers, respiratory chain (RC) activity) were performed at baseline, after the intervention and after a 6 month wash-out period. Compared with omnivores, vegans had higher IS at baseline (GIR, glucose infusion rate: 9.6±2.4 vs 7.1±2.4 mg/kg/min, 95% CI for difference: 0.55 to 5.82) that declined after the intervention and returned to baseline values after the wash-out period (changes in GIR with 95% CI, 3-0 months: -1.64 [-2.5; -0.75] and 9-3 months: 1.65 [0.75; 2.54] mg/kg/min). No such change was observed in omnivores. In omnivores the intervention led to an increased expression of lipogenic genes (DGAT2, FASN, PPARγ, SCD1) in AT. SM RC activity increased in both groups. Negative impact of increased BCAA intake on IS was only detected in vegans, that is, subjects with low basal amino acids/BCAA intake, which appear to be unable to induce sufficient compensatory changes within AT and SM on a BCAA challenge.

Periodic minimal surfaces

NASA Astrophysics Data System (ADS)

Mackay, Alan L.

1985-04-01

A minimal surface is one for which, like a soap film with the same pressure on each side, the mean curvature is zero and, thus, is one where the two principal curvatures are equal and opposite at every point. For every closed circuit in the surface, the area is a minimum. Schwarz1 and Neovius2 showed that elements of such surfaces could be put together to give surfaces periodic in three dimensions. These periodic minimal surfaces are geometrical invariants, as are the regular polyhedra, but the former are curved. Minimal surfaces are appropriate for the description of various structures where internal surfaces are prominent and seek to adopt a minimum area or a zero mean curvature subject to their topology; thus they merit more complete numerical characterization. There seem to be at least 18 such surfaces3, with various symmetries and topologies, related to the crystallographic space groups. Recently, glyceryl mono-oleate (GMO) was shown by Longley and McIntosh4 to take the shape of the F-surface. The structure postulated is shown here to be in good agreement with an analysis of the fundamental geometry of periodic minimal surfaces.

Effects of atrial fibrillation on myocardial washout rate of thallium-201 on myocardial perfusion single-photon emission computed tomography.

PubMed

Kurisu, Satoshi; Nitta, Kazuhiro; Sumimoto, Yoji; Ikenaga, Hiroki; Ishibashi, Ken; Fukuda, Yukihiro; Kihara, Yasuki

2018-04-20

Myocardial perfusion single-photon emission computed tomography (SPECT) with thallium (Tl)-201 is an established modality for evaluating myocardial ischemia. We assessed the effects of atrial fibrillation (AF) on the myocardial washout rate (WR) of Tl-201 on myocardial perfusion SPECT. A total of 231 patients with no evidence of myocardial ischemia were enrolled retrospectively in this study. Patients were divided into two groups on the basis of the ECG at the time of myocardial perfusion SPECT. The mean myocardial WR of Tl-201 was calculated from the stress and the redistribution Bull's eye maps. There were 34 patients with AF and 197 patients with sinus rhythm. There were no significant differences in clinical variables, except for older age and higher heart rate in patients with AF. Myocardial WR of Tl-201 was significantly lower in patients with AF than those with sinus rhythm (46±12 vs. 51±8%, P=0.03). Multivariate analysis including these factors showed that female sex (β=0.18, P=0.02), AF (β=-0.14 P=0.03), hemoglobin (β=-0.18, P<0.01), and serum creatinine (β=0.24, P<0.01) were determinants of myocardial WR of Tl-201. Our data suggest that AF is associated with reduced myocardial WR of Tl-201 on myocardial perfuison SPECT.

Cross-national and historical differences in subjective well-being.

PubMed

Jorm, Anthony F; Ryan, Siobhan M

2014-04-01

There is a growing body of population survey data on national subjective well-being which allows comparisons across countries and across periods. Key issues in this work are as follows. Can response to questions on well-being be meaningfully compared across countries and periods? What social conditions are associated with greater well-being both between countries and across periods? Are there lessons for how global well-being might be improved? This review aims to give an overview of this area and its relevance to psychiatric epidemiology. Systematic searches of the literature were carried out using eight academic databases between August 2012 and January 2013. Subjective well-being involves multiple components, including cognitive evaluation of satisfaction with life and emotional state, and these are separable from mental ill health. Although there are difficulties in measuring subjective well-being in comparable ways cross-culturally, there is sufficient evidence of validity to make comparisons meaningful. The subjective well-being of nations increases with income per capita, but gains are smaller in higher-income countries. Other national factors that affect well-being include income inequality, social welfare, individualism, democracy and freedom, social capital and physical health. Economic growth of lower-income nations will improve global subjective well-being. However, this needs to be sustainable or it will reduce the well-being of future generations. Higher-income nations need to focus on other determinants of well-being. Research on cross-national well-being suggests a number of directions that may be profitably pursued in psychiatric epidemiology.

46 CFR 15.1111 - Work hours and rest periods.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Work hours and rest periods. 15.1111 Section 15.1111 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Vessels Subject to Requirements of STCW § 15.1111 Work hours and rest periods. (a) Each person...

46 CFR 15.1111 - Work hours and rest periods.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Work hours and rest periods. 15.1111 Section 15.1111 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Vessels Subject to Requirements of STCW § 15.1111 Work hours and rest periods. (a) Each person...

46 CFR 15.1111 - Work hours and rest periods.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Work hours and rest periods. 15.1111 Section 15.1111 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Vessels Subject to Requirements of STCW § 15.1111 Work hours and rest periods. (a) Each person...

46 CFR 15.1111 - Work hours and rest periods.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Work hours and rest periods. 15.1111 Section 15.1111 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN MANNING REQUIREMENTS Vessels Subject to Requirements of STCW § 15.1111 Work hours and rest periods. (a) Each person...

The effect of fish oil supplements on blood pressure.

PubMed Central

Lofgren, R P; Wilt, T J; Nichol, K L; Crespin, L; Pluhar, R; Eckfeldt, J

1993-01-01

We conducted a double-blind, placebo-controlled crossover study to determine the effects of fish oil supplementation on blood pressure in middle-aged men. Subjects were randomly assigned to consume either 20 g of fish oil or safflower oil for 12 weeks and then consume the other oil for an additional 12 weeks after a 4-week washout period. We found no significant changes from the pretreatment value in systolic or diastolic blood pressure with the use of fish oil supplements. In addition, there were no significant differences in the posttreatment blood pressures comparing the fish and safflower oil phases of the study. PMID:8427339

Neither hereditary periodic fever nor periodic fever, aphthae, pharingitis, adenitis: Undifferentiated periodic fever in a tertiary pediatric center

PubMed Central

De Pauli, Silvia; Lega, Sara; Pastore, Serena; Grasso, Domenico Leonardo; Bianco, Anna Monica Rosaria; Severini, Giovanni Maria; Tommasini, Alberto; Taddio, Andrea

2018-01-01

AIM To describe the frequency and clinical characteristics of patients with undifferentiated periodic fever (UPF) and to investigate whether a clinical classification of UPF based on the PRINTO-Eurofever score can help predicting the response to treatment and the outcome at follow-up. METHODS Clinical and therapeutic information of patients with recurrent fever who presented at a single pediatric rheumatology center from January 2006 through April 2016 were retrospectively collected. Patients with a clinical suspicion of hereditary periodic fever (HPF) syndrome and patients with clinical picture of periodic fever, aphthae, pharingitis, adenitis (PFAPA) who were refractory to tonsillectomy underwent molecular analysis of five HPF-related genes: MEFV (NM_000243.2), MVK (NM_000431.3), TNFRSF1A (NM_001065.3), NLRP3 (NM_001079821.2), NLRP12 (NM_001277126.1). All patients who had a negative genetic result were defined as UPF and further investigated. PRINTO-Eurofever score for clinical diagnosis of HPF was calculated in all cases. RESULTS Of the 221 patients evaluated for periodic fever, twelve subjects with a clinical picture of PFAPA who were refractory to tonsillectomy and 22 subjects with a clinical suspicion of HPF underwent genetic analysis. Twenty-three patients (10.4%) resulted negative and were classified as UPF. The median age at presentation of patients with UPF was 9.5 mo (IQR 4-24). Patients with UPF had a higher frequency of aphthae (52.2% vs 0%, P = 0.0026) and musculoskeletal pain (65.2% vs 18.2%, P = 0.0255) than patients with genetic confirmed HPF. Also, patients with UPF had a higher frequency of aphthous stomatitis (52.2% vs 10.7%, P < 0.0001), musculoskeletal pain (65.2% vs 8,0%, P < 0.0001), and abdominal pain (52.2% vs 4.8%, P < 0.0001) and a lower frequency of pharyngitis (56.6% vs 81.3%, P = 0.0127) compared with typical PFAPA in the same cohort. Twenty-one of 23 patients with UPF (91.3%) received steroids, being effective in 16; 13 (56.2%) were

Effects of rinsing with arginine bicarbonate and urea solutions on initial enamel lesions in situ.

PubMed

Yu, Y; Wang, X; Ge, C; Wang, B; Cheng, C; Gan, Y-H

2017-04-01

The aim of this study was to investigate the effects of rinsing with arginine or urea solution on initial enamel lesions in situ. Fourteen subjects who wore mandibular removable partial dentures embedded with bovine enamel blocks with artificial enamel lesions were included. The experiment included four 4-week rinsing periods with a 10-day washout period between each rinsing period. In each rinsing period, the subjects rinsed after meal or snack using water, or 2% arginine bicarbonate, or 1% urea, or 0.05% NaF solution, five times daily. The mineralization changes of the enamel lesions were assessed using quantitative light-induced fluorescence. All groups except the water group showed a statistically significant decrease in the fluorescence loss after treatment, compared with their respective baseline. Although both the arginine group and urea group showed more decrease in fluorescence loss than that of the water group, the decrease was not statistically significantly different from that of the water group. The decrease in fluorescence loss of the NaF group was statistically significant than that of the water group, arginine group, and urea group. Rinsing with arginine or urea solution offers limited remineralizing benefit to enamel lesions over a period of 4-week time. © 2016 The Authors. Oral Diseases Published by John Wiley & Sons Ltd.

Predictors of Nightly Subjective-Objective Sleep Discrepancy in Poor Sleepers over a Seven-Day Period

PubMed Central

Herbert, Vanessa; Pratt, Daniel; Emsley, Richard; Kyle, Simon D.

2017-01-01

This study sought to examine predictors of subjective/objective sleep discrepancy in poor sleepers. Forty-two individuals with insomnia symptoms (mean age = 36.2 years, 81% female) were recruited to take part in a prospective study which combined seven days of actigraphy with daily assessment of sleep perceptions, self-reported arousal, sleep effort, and mood upon awakening. A high level of intra-individual variability in measures of sleep discrepancy was observed. Multilevel modelling revealed that higher levels of pre-sleep cognitive activity and lower mood upon awakening were significantly and independently predictive of the underestimation of total sleep time. Greater levels of sleep effort predicted overestimation of sleep onset latency. These results indicate that psychophysiological variables are related to subjective/objective sleep discrepancy and may be important therapeutic targets in the management of insomnia. PMID:28282912

Punctuation in Library of Congress Subject Headings

ERIC Educational Resources Information Center

Steinweg, Hilda

1978-01-01

An analysis of the punctuation of the eighth edition Library of Congress Subject Headings reveals that the hyphen, coma and parentheses are most often used. Examples of these and the use of the apostrophe, dash, and period are discussed. (Author/MBR)

Eating a healthy lunch improves serum alanine aminotransferase activity.

PubMed

Iwamoto, Masako; Yagi, Kaori; Yazumi, Kayoko; Komine, Airi; Shirouchi, Bungo; Sato, Masao

2013-09-14

Nutritional guidance and diet control play important roles in the treatment of obesity and non-alcoholic fatty liver. However, in Japan, nutritional guidance is difficult to provide in practice. Therefore, we evaluated the effects of providing the 'once-a-day' intervention of a healthy lunch on various metabolic parameters. For a 1-month preparatory period, 10 subjects generally consumed the lunches that were provided by the worksite cafeteria. This was followed by a 1-week washout period, after which, the subjects consumed healthy, low-calorie, well-balanced lunches for a 1-month test period. After the preparatory and test periods, blood samples were obtained from all subjects. The serum levels of indices relevant to metabolic syndrome and fatty liver were measured. Serum alanine aminotransferase activity significantly decreased by 20.3% after the healthy intervention. However, the indices of metabolic syndrome did not significantly change. Analysis of the relationship between serum alanine aminotransferase activity and nutrient content indicated that the improvement of serum alanine aminotransferase status was due to the higher vegetable content and lower animal-source protein of the meals provided. In summary, the 'once-a-day' intervention of providing a healthy lunch improved serum alanine aminotransferase status. A diet high in vegetables and low in animal-based protein is important in maintaining a healthy condition.

Physiological Responses to Two Hypoxic Conditioning Strategies in Healthy Subjects.

PubMed

Chacaroun, Samarmar; Borowik, Anna; Morrison, Shawnda A; Baillieul, Sébastien; Flore, Patrice; Doutreleau, Stéphane; Verges, Samuel

2016-01-01

Objective: Hypoxic exposure can be used as a therapeutic tool by inducing various cardiovascular, neuromuscular, and metabolic adaptations. Hypoxic conditioning strategies have been evaluated in patients with chronic diseases using either sustained (SH) or intermittent (IH) hypoxic sessions. Whether hypoxic conditioning via SH or IH may induce different physiological responses remains to be elucidated. Methods: Fourteen healthy active subjects (7 females, age 25 ± 8 years, body mass index 21.5 ± 2.5 kg·m -2 ) performed two interventions in a single blind, randomized cross-over design, starting with either 3 x SH (48 h apart), or 3 x IH (48 h apart), separated by a 2 week washout period. SH sessions consisted of breathing a gas mixture with reduced inspiratory oxygen fraction (FiO 2 ), continuously adjusted to reach arterial oxygen saturations (SpO 2 ) of 70-80% for 1 h. IH sessions consisted of 5 min with reduced FiO 2 (SpO 2 = 70-80%), followed by 3-min normoxia, repeated seven times. During the first (S1) and third (S3) sessions of each hypoxic intervention, cardiorespiratory parameters, and muscle and pre-frontal cortex oxygenation (near infrared spectroscopy) were assessed continuously. Results : Minute ventilation increased significantly during IH sessions (+2 ± 2 L·min -1 ) while heart rate increased during both SH (+11 ± 4 bpm) and IH (+13 ± 5 bpm) sessions. Arterial blood pressure increased during all hypoxic sessions, although baseline normoxic systolic blood pressure was reduced from S1 to S3 in IH only (-8 ± 11 mmHg). Muscle oxygenation decreased significantly during S3 but not S1, for both hypoxic interventions (S3: SH -6 ± 5%, IH -3 ± 4%); pre-frontal oxygenation decreased in S1 and S3, and to a greater extent in SH vs. IH (-13 ± 3% vs. -6 ± 6%). Heart rate variability indices indicated a significantly larger increase in sympathetic activity in SH vs. IH (lower SDNN, PNN50, and RMSSD values in SH). From S1 to S3, further reduction in heart

Comparative effect of fluoride, essential oil and chlorhexidine mouth rinses on dental plaque and gingivitis in patients with and without dental caries: a randomized controlled trial.

PubMed

Charugundla, B R; Anjum, S; Mocherla, M

2015-05-01

The objective of this study was to compare the effectiveness of fluoride, essential oil (EO) and chlorhexidine (CHX)-containing mouth rinses on dental plaque and gingivitis and to compare their relative efficacy in patients with and without dental caries. A randomized, controlled, double- blind, crossover clinical trial was conducted for a period of 8 weeks. Thiry-six qualifying subjects, aged 12-44 years, were included in the study. Subjects were divided into caries and caries-free groups and were randomly assigned to one of the following mouth rinse groups: fluoride; EO; CHX and saline as negative control. Subjects used their respective mouth rinse for a period of 7-days each with 1-week wash-out periods. Primary efficacy variables were Quigley-Hein plaque index (PI) and Loe and Silness gingival index. Fluoride and CHX mouth rinses showed significant reduction in plaque after use of mouth rinses (P < 0.05). However, no significant differences were observed with respect to each other in reducing gingivitis (P > 0.05). Further significant differences were found in reducing plaque and gingivitis in caries-free subjects in comparison to those with caries (P < 0.05). All the three mouth rinses significantly reduced plaque accumulation and gingivitis especially in caries-free subjects in comparison to those with caries, and amongst the three, fluoride and CHX proved to be more effective than EO mouth rinse. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The bile acid turnover rate assessed with the (75)SeHCAT test is stable in chronic diarrhoea but slightly decreased in healthy subjects after a long period of time.

PubMed

Bajor, Antal; Kilander, Anders; Sjövall, Henrik; Rudling, Mats; Ung, Kjell-Arne

2008-11-01

The stability of bile acid turnover rate was evaluated retrospectively using repeat SeHCAT tests in patients with chronic diarrhoea and prospectively for 16 years in healthy subjects. The SeHCAT values were stable in 39 patients with chronic diarrhoea, as shown by a comparison of the test results [data presented as median and (25th-75th percentile)]: 18% (8-23) in the first test versus 14% (9-21) in the second test [n = 39, P = 0.37, time interval 44 months (16-68), repeatability index >95%]. In contrast, they were reduced after 16 years in healthy subjects: 38% (30-49.5) in the first test versus 31% (21-49.5) in the second test (P < 0.03). In healthy subjects, the body mass index increased by 13% from 23.2 kg/m(2) (21-24.6) to 26.2 kg/m(2) (22.5-27.8) (P < 0.01) during the 16 years. There was a negative correlation between hepatic bile acid synthesis and the SeHCAT values (r = -0.615, P = 0.02, n = 14). In conclusion, the turnover rate of bile acids is stable over a long period of time in patients with chronic diarrhoea irrespective of bile acid malabsorption, suggesting that a repeat SeHCAT test is dispensable. There is a significant negative correlation between bile acid synthesis and SeHCAT test results in healthy subjects. The SeHCAT test values are slightly reduced in healthy subjects after 16 years.

Desipramine restricts estral cycle oscillations in swimming.

PubMed

Contreras, C M; Martínez-Mota, L; Saavedra, M

1998-10-01

1. Desipramine (DMI) is a tricyclic antidepressant which reduces the immobility in rats forced to swim; however, it is unknown whether estral cycle phases impinge on DMI actions on immobility in daily swimming tests during several weeks. 2. In female wistar rats, vaginal smears taken before testing defined four estral phases. Afterwards, the authors assessed the latency for the first period of immobility in five-min forced swim tests practiced on 21-day DMI (DMI group), 21-day washout saline given after a 21-day DMI treatment (washout-saline group), or non-treated rats (control group). 3. We observed a longer latency for the first period of immobility in proestrus-estrus from the control and washout-saline groups. The 21-day treatment with DMI (2.1 mg/kg i.p., once a day) significantly (p < 0.001) increased the latency by about 160% from control regardless of the estral cycle phase. 4. It is concluded that proestrus-estrus relates to increased struggling behavior. DMI enhances struggling behavior independently of hormonal state.

Effect of alcohol consumption on the liver detoxication capacity as measured by [13C2]aminopyrine and L-[1-13C]phenylalanine breath tests.

PubMed

Wutzke, Klaus D; Wigger, Marianne

2009-09-01

The aim of this study was to investigate the hepatic microsomal and cytosolic functions by using the 13CO2 breath test in healthy subjects either before or after consumption of red wine. Twelve adults received [13C2]aminopyrine and L-[1-13C]phenylalanine together with a standardised dinner. Expired air samples were taken over 6 h. After a wash-out period, the subjects consumed 0.4 ml ethanol per kg per day together with dinner over a 7.5-day period on average. Thereafter, 13C-tracer administration was repeated under identical conditions. The 13CO2 enrichments were measured by isotope ratio mass spectrometry. The mean cumulative percentage 13C-dose recovery after administration of [13C2]aminopyrine and L-[1-13C]phenylalanine either without or with red wine consumption amounted to 17.0+/-4.4 vs. 14.7+/-3.1% (p=0.170) and 14.0+/-2.8 vs. 11.5+/-3.9% (p=0.084), respectively. Moderate alcohol consumption does not induce significant short-term changes of the microsomal and the cytosolic function of the human liver in healthy subjects.

[The role of CD14 promoter - 159 C-> T polymorphism on changes of serum lipid ratios induced by high-carbohydrate/low-fat diets in healthy Chinese Han youth].

PubMed

Jiang, Zhe; Gong, Ren-rong; Li, Yuan-hao; Fan, Mei; Fang, Ding-zhi

2012-05-01

To investigate the role of CD14 promoter - 159 C-> T polymorphism on ratios of serum lipids and its interaction on the ratios with a high-carbohydrate/low-fat (HC/LF) diet in a young and healthy Chinese Han population. After a washout diet for seven days, fifty six healthy young subjects (22.89 +/- 1.80 years) were given the HC/LF diet for six days. Twelve-hour fasting venous blood samples were collected in the mornings of the first, the eighth and the fourteenth days. The serum lipid profiles and the CD14 -159 C->T polymorphism were analyzed. The ratios of triglyceride/high density lipoprotein-cholesterol (TG/HDL-c), log (TG/HDL-c), total cholesterol/high density lipoprotein-cholesterol (TC/HDL-c) and low density lipoprotein-cholesterol/high density lipoprotein-cholesterol (LDL-c/HDL-c) were calculated. The male carriers of the C allele had significantly higher TG/HDL-c and log (TG/HDL-c) than the female carriers at baseline, after the washout diet and after the HC/LF diet, higher TC/HDL-c at baseline and after the washout diet, and higher LDL-c/HDL-c only after the washout diet. The female subjects with the TT genotype had higher TG/HDL-c and log (TG/HDL-c) than the female carriers of the C allele at baseline, after the washout diet and after the HC/LF diet, higher LDL-c/HDL-c at baseline and after the HC/LF diet, and higher TC/HDL-c only after the washout diet. Compared with that before the HC/LF diet, TC/HDL-c was significantly decreased after the HC/LF diet regardless of gender and the genotype of the CD14 -159 polymorphism. LDL-c/HDL-c was significantly decreased in both the male and female carriers of the C allele. TG/HDL-c and log (TG/HDL-c) were significantly increased only in the female carriers of the C allele. In the subjects with C allele, the HC/LF diet is a minor factor and its effects on the lipid ratios can be masked by the effects of the C allele at CD14 -159. The interaction between the HC/LF diet and the C allele at CD14 -159 can decrease LDL

Comparative bioavailability and pharmacokinetics of two oral formulations of flurbiprofen: a single-dose, randomized, open-label, two-period, crossover study in Pakistani subjects.

PubMed

Qayyum, Aisha; Najmi, Muzammil Hasan; Abbas, Mateen

2013-11-01

Comparative bioavailability studies are conducted to establish the bioequivalence of generic formulation with that of branded reference formulation, providing confidence to clinicians to use these products interchangeably. This study was carried out to compare a locally manufactured formulation of flurbiprofen with that of a branded product. Twenty two healthy male adults received a single dose of flurbiprofen (100mg) either generic or branded product according to randomization scheme on each of 2 periods. Blood samples were collected and plasma flurbiprofen concentration was determined by a validated HPLC method. Pharmacokinetic parameters like AUC(0-t), AUC(0-oo), Cmax, Tmax, t½, Vd and clearance were determined. The 90% CI for the ratio of geometric means of test to reference product's pharmacokinetic variables was calculated. Pharmacokinetic parameters for two formulations were comparable. Ratio of means of AUC(0-24), AUC(0-oo) and Cmax for test to reference products and 90% CI for these ratios were within the acceptable range. The p-values calculated by TOST were much less than the specified value (p-0.05). ANOVA gave p-values which were more than the specified value (p-0.05) for sequence, subject, period and formulation. Test formulation of flurbiprofen (tablet Flurso) was found to meet the criteria for bioequivalence to branded product (tablet Ansaid) based on pharmacokinetic parameters.

Rapid distortion analysis of high speed homogeneous turbulence subject to periodic shear

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertsch, Rebecca L., E-mail: rlb@lanl.gov; Girimaji, Sharath S., E-mail: girimaji@aero.tamu.edu

2015-12-15

The effect of unsteady shear forcing on small perturbation growth in compressible flow is investigated. In particular, flow-thermodynamic field interaction and the resulting effect on the phase-lag between applied shear and Reynolds stress are examined. Simplified linear analysis of the perturbation pressure equation reveals crucial differences between steady and unsteady shear effects. The analytical findings are validated with numerical simulations of inviscid rapid distortion theory (RDT) equations. In contrast to steadily sheared compressible flows, perturbations in the unsteady (periodic) forcing case do not experience an asymptotic growth phase. Further, the resonance growth phenomenon found in incompressible unsteady shear turbulence ismore » absent in the compressible case. Overall, the stabilizing influence of both unsteadiness and compressibility is compounded leading to suppression of all small perturbations. The underlying mechanisms are explained.« less

Braille character discrimination in blindfolded human subjects.

PubMed

Kauffman, Thomas; Théoret, Hugo; Pascual-Leone, Alvaro

2002-04-16

Visual deprivation may lead to enhanced performance in other sensory modalities. Whether this is the case in the tactile modality is controversial and may depend upon specific training and experience. We compared the performance of sighted subjects on a Braille character discrimination task to that of normal individuals blindfolded for a period of five days. Some participants in each group (blindfolded and sighted) received intensive Braille training to offset the effects of experience. Blindfolded subjects performed better than sighted subjects in the Braille discrimination task, irrespective of tactile training. For the left index finger, which had not been used in the formal Braille classes, blindfolding had no effect on performance while subjects who underwent tactile training outperformed non-stimulated participants. These results suggest that visual deprivation speeds up Braille learning and may be associated with behaviorally relevant neuroplastic changes.

Exact states in waveguides with periodically modulated nonlinearity

NASA Astrophysics Data System (ADS)

Ding, E.; Chan, H. N.; Chow, K. W.; Nakkeeran, K.; Malomed, B. A.

2017-09-01

We introduce a one-dimensional model based on the nonlinear Schrödinger/Gross-Pitaevskii equation where the local nonlinearity is subject to spatially periodic modulation in terms of the Jacobi {dn} function, with three free parameters including the period, amplitude, and internal form-factor. An exact periodic solution is found for each set of parameters and, which is more important for physical realizations, we solve the inverse problem and predict the period and amplitude of the modulation that yields a particular exact spatially periodic state. A numerical stability analysis demonstrates that the periodic states become modulationally unstable for large periods, and regain stability in the limit of an infinite period, which corresponds to a bright soliton pinned to a localized nonlinearity-modulation pattern. The exact dark-bright soliton complex in a coupled system with a localized modulation structure is also briefly considered. The system can be realized in planar optical waveguides and cigar-shaped atomic Bose-Einstein condensates.

Zeaxanthin-based dietary supplement and topical serum improve hydration and reduce wrinkle count in female subjects.

PubMed

Schwartz, Steve; Frank, Emily; Gierhart, Dennis; Simpson, Paula; Frumento, Robert

2016-12-01

Dietary modification, through supplementation and elimination diets, has become an area of interest to help slow skin aging, reduce symptom severity or prevent reoccurrence of certain dermatologic conditions [Clinical Dermatology vol. 31 (2013) 677-700]. Free radical components (reactive oxygen species or ROS) or lipid peroxide (LPO) is involved in the pathogenesis and progression of accelerated skin aging when prolonged oxidative stress occurs. The use of antioxidant-related therapies such as nutraceuticals is of particular interest in restoring skin homeostasis. Antioxidant carotenoid zeaxanthin is concentrated in the eye and skin tissue and believed to decrease the formation of ROS associated with UV light exposure. With zeaxanthin, phytoceramides, and botanical extracts an oral and topical test product (with zeaxanthin, algae extracts, peptides, hyaluronate) have been developed to improve the appearance and condition of skin when used as directed. Subjects were divided into three groups: two tests (skin formula 1 - oral product alone (ZO-1), skin formula 2- oral product with topical product (ZO-2 + ZT)), and one placebo control. The study consisted of a washout visit, baseline (randomization), week two (2), week four (4), week six (6), week eight (8), and week twelve (12). Key parameters measured were as follows: fine lines, deep lines, total wrinkles, wrinkle severity, radiance/skin color (L, a*, b*), discolorations, and skin pigment homogeneity. Thirty-one subjects completed the twelve-week study; no adverse events were recorded during the study. Statistically significant improvements from baseline mean hydration score were observed in active groups at weeks 2, 6, and 8. A statistically significant difference was observed between mean differences from baseline scores for total wrinkle count at week 4 for the combination active groups compared to placebo. A statistically significant difference from baseline scores for fine lines count was also observed at

Effects of partial replacement of dietary fat by olestra on dietary cholesterol absorption in man

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jandacek, R.J.; Ramirez, M.M.; Crouse, J.R. III

1990-08-01

Olestra, a nonabsorbable fat substitute comprising long-chain fatty acid esters of sucrose, had been previously shown to reduce cholesterol absorption in humans when ingested at a level of 50 g/d. To determine whether or not a lower level of dietary olestra would also reduce cholesterol absorption, we studied the effect of 7 g of olestra twice a day in 20 normocholesterolemic male inpatients in a double-blind, crossover trial. Two 6-day diet treatment and stool collection periods were separated by a 14-day washout period. Half of the subjects received butter, and half, a butter-olestra blend during each treatment period according tomore » a crossover design. All subjects ingested trace amounts of 3H-cholesterol and 14C-beta-sitosterol with the butter or the butter-olestra blend. Cholesterol absorption was determined from the 3H/14C ratios in the diet and in saponified and extracted stools according to previously validated methodology. Cholesterol absorption during the butter regimen was significantly greater than that during the olestra regimen (56.1% +/- 1.6% v 46.7% +/- 1.1%, P less than .01).« less

Effect of ewe’s (semi-skimmed and whole) and cow’s milk yogurt consumption on the lipid profile of control subjects: a crossover study

PubMed Central

Olmedilla-Alonso, Begoña; Nova-Rebato, Esther; García-González, Natalia; Martín-Diana, Ana-Belén; Fontecha, Javier; Delgado, David; Gredilla, Ana-Elisa; Bueno, Francisco; Asensio-Vegas, Carmen

2017-01-01

ABSTRACT Yogurt is the most widely consumed fermented milk product worldwide. Studies have mainly used milk and dairy products from cow, which have a lower fat content than those from ewe and a different lipid profile. This study investigated the effect on the lipid profile of control subjects of three different set yogurts: (a) semi-skimmed ewe´s milk yogurt (2.8% milk fat); (b) whole ewe´s milk yogurt (5.8 % milk fat); (c) cow´s milk yogurt (3 % milk fat). A randomized crossover study included 30 healthy adults (16 women) to consume 250 g/yogurt/day during three consecutive 5-weeks periods separated by 4-week washouts. Blood samples were collected at the start and end of each period for the analysis of serum cholesterol (total, HDL-, LDL-) and triglycerides. We found no differences in the serum concentrations of lipid and lipoprotein fractions of the volunteers after the intake of any of the three types of yogurts. When the volunteers were grouped into two risk groups of risk according to their total cholesterol/HDL cholesterol ratio, the same differences between the groups in terms of the cholesterol (HDL-, LDL-) and triglyceride responses at baseline and after yogurt intake were found, with no effects due to the different types of yogurts. Moreover, we performed compositional analysis of the yogurts including determination of protein, fat, minerals and fatty acids (FA). Contents in protein, calcium, magnesium, non-protein nitrogen and some FA (mainly short-chain-FA) were higher for ewe’s than for cow’s milk yogurt. n6-n3 ratio was lower in the ewe’s milk yogurt. In conclusion, yogurt intake, from ewe’s and cow’s milk, at levels of consumption compatible with a varied diet, neither decreases nor increases plasma lipoprotein cholesterol levels in apparently healthy individuals. As ewe’s milk yogurt has a high content of macro- and micronutrients, certain target populations could benefit from its consumption. PMID:29151833

Subjective Response to Simulated Sonic Booms in Homes

NASA Technical Reports Server (NTRS)

McCurdy, David A.; Brown, Sherilyn A.

1996-01-01

One of the environmental issues affecting the development of a second-generation supersonic commercial transport is the impact of sonic booms on people. Aircraft designers are attempting to design the transport to produce sonic boom signatures that will have minimum impact on the public. Current supersonic commercial aircraft produce an 'N-wave' sonic boom pressure signature that is considered unacceptable by the public. This has resulted in first-generation supersonic transports being banned from flying supersonic over land in the United States, a severe economic constraint. By tailoring aircraft volume and lift distributions, designers hope to produce sonic boom signatures having specific shapes other than 'N-wave' that may be more acceptable to the public. As part of the effort to develop a second-generation supersonic commercial transport, Langley Research Center is conducting research to study people's subjective response to sonic booms. As part of that research, a system was developed for performing studies of the subjective response of people to the occurrence of simulated sonic booms in their homes. The In-Home Noise Generation/Response System (IHONORS) provides a degree of situational realism not available in the laboratory and a degree of control over the noise exposure not found in community surveys. The computer-controlled audio system generates the simulated sonic booms, measures the noise levels, and records the subjects' ratings and can be placed and operated in individual homes for extended periods of time. The system was used to conduct an in-home study of subjective response to simulated sonic booms. The primary objective of the study was to determine the effect on annoyance of the number of sonic boom occurrences in a realistic environment. The effects on annoyance of several other parameters were also examined. Initially, data analyses were based on all the data collected. However, further analyser found that test subjects adapted to the sonic

Cross-over assessment of serum bactericidal activity of moxifloxacin and levofloxacin versus penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae in healthy volunteers.

PubMed

Hart, Daniel; Weinstein, Melvin P

2007-07-01

We compared the serum bactericidal activity (SBA) of moxifloxacin and levofloxacin against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae in 12 healthy volunteers. Each subject received 3 days of oral moxifloxacin 400 mg daily and levofloxacin 750 mg daily, respectively, with a 2- to 4-week washout period between regimens. Blood was drawn at 6 time points after the third dose of each antibiotic. Mean serum bactericidal titers (MSBTRs) for moxifloxacin were 4-fold higher than the mean titers for levofloxacin at each time point. For each drug, MSBTRs at each time point were the same or within one 2-fold dilution when analyzed according to the penicillin susceptibility of the strains or the sex of the subjects. The difference in SBA of the 2 drugs may have implications for the emergence of resistance and clinical outcome.

Rapid distortion analysis of high speed homogeneous turbulence subject to periodic shear

DOE PAGES

Bertsch, Rebecca L.; Girimaji, Sharath S.

2015-12-30

The effect of unsteady shear forcing on small perturbation growth in compressible flow is investigated. In particular, flow-thermodynamic field interaction and the resulting effect on the phase-lag between applied shear and Reynolds stress are examined. Simplified linear analysis of the perturbation pressure equation reveals crucial differences between steady and unsteady shear effects. The analytical findings are validated with numerical simulations of inviscid rapid distortion theory (RDT) equations. In contrast to steadily sheared compressible flows, perturbations in the unsteady (periodic) forcing case do not experience an asymptotic growth phase. Further, the resonance growth phenomenon found in incompressible unsteady shear turbulence ismore » absent in the compressible case. Overall, the stabilizing influence of both unsteadiness and compressibility is compounded leading to suppression of all small perturbations. As a result, the underlying mechanisms are explained.« less

Exposure to formaldehyde: effects on pulmonary function.

PubMed

Alexandersson, R; Hedenstierna, G; Kolmodin-Hedman, B

1982-01-01

Forty-seven subjects exposed to formaldehyde (mean air concentration 0.45 mg/m3) and 20 unexposed subjects, all of whom were employed at a carpentry shop, were studied with regard to symptoms and pulmonary function. Symptoms involving eyes and throat as well as chest oppression were significantly more common in the exposed subjects than in the unexposed controls. Spirometry and single breath nitrogen washout were normal Monday morning before exposure to formaldehyde. A reduction in forced expiratory volume in 1 sec by an average of 0.2 L (P = .002), percent forced expiratory volume by 2% (P = .04), maximum midexpiratory flow by 0.3 L/sec (P = .04) and an increase in closing volume in percentage of vital capacity by 3.4% (P - .002) were seen after a day of work and exposure to formaldehyde, suggesting bronchoconstriction. Smokers and nonsmokers displayed similar changes in spirometry and nitrogen washout.

The circadian rhythms of human subjects without timepieces or indication of the alternation of day and night

PubMed Central

Mills, J. N.; Minors, D. S.; Waterhouse, J. M.

1974-01-01

1. Seven solitary subjects, and two groups of four, spent from 5 to 13 days in an isolation unit without knowledge of time. Three solitary subjects and one group of four adopted fairly regular activity habits with a period of 25-27 h; one subject adopted a period of 30 h, and one of 27 h initially, decreasing to 24-25 h after a few days. One group of four awoke roughly every 24 h, after a sleep which was alternately about 8 h, or about 4 h and believed by the subjects to be an afternoon siesta. Two solitary subjects alternated sleeps of about 8 or 16 h, separated by 24 h of activity. 2. Deep temperature in all subjects oscillated with a period of 24-26 h, which was thus commonly distinct from their activity habits. 3. Urinary potassium followed a rhythm whose period, though usually close to, was sometimes distinct from, that of temperature. A secondary period corresponding to that of activity was also sometimes present. 4. Urinary sodium and chloride usually gave evidence of two periodic components, one corresponding to activity and the other to the rhythm of either temperature or of urinary potassium. 5. Urinary creatinine and phosphate usually followed the subject's routine of activity. 6. Plasma samples were collected on a few occasions and analysed for phosphate and 11-hydroxycorticosteroids. Changes in plasma phosphate were usually, but not always, associated with similar changes in urinary phosphate, and changes in plasma corticosteroids were often, but not always, associated with similar changes in urinary potassium shortly afterwards. 7. Observations are recorded on a subject alone in a cave for 127 days. His activity habits, though wildly variable, gave evidence of a period of 25·1 h and his urinary electrolyte excretion indicated a shorter period, of 24·6 h. During the following 3 days, when he remained in the cave but was visited frequently, his plasma corticosteroids and urinary potassium oscillated with a period of 16 h. 8. The possible mechanisms

Safety and Efficacy of an Artificial Tear Containing 0.3% Hyaluronic Acid in the Management of Moderate-to-Severe Dry Eye Disease.

PubMed

López-de la Rosa, Alberto; Pinto-Fraga, José; Blázquez Arauzo, Francisco; Urbano Rodríguez, Rubén; González-García, María J

2017-11-01

To evaluate the safety and efficacy of a new 0.3% hyaluronic acid artificial tear compared with 0.9% saline solution (0.9% NaCl) in moderate-to-severe dry eye patients after 1 month's use. A total of 16 patients with moderate-to-severe dry eye were included in this crossover study. After a 1-week washout period, patients used the experimental (Visaid 0.3%) or control solution (0.9% NaCl), selected randomly, applying three to eight drops daily for a month. After another washout period, patients used the other solution in the same way. Percentage of change (ΔY) was calculated and analyzed for (1) safety variables: visual acuity, intraocular pressure, and ophthalmoscopy evaluation; (2) efficacy variable: Ocular Surface Disease Index (OSDI) questionnaire; and (3) secondary variables: biomicroscopy findings, fluorescein corneal staining, lissamine green conjunctival staining, tear breakup time (TBUT), contrast sensitivity, Schirmer test, and subject satisfaction. There were no significant differences in the safety parameters for either solution. After using Visaid 0.3%, patients showed significant improvements in OSDI score (ΔY: -9.66%±10.90), tarsal hyperemia (ΔY: -16.67%±27.89), corneal staining extension (ΔY: -34.90%±42.41), TBUT (ΔY: 13.98%±26.19), and subjective satisfaction (ΔY: 38.06%±47.06). When using 0.9% NaCl, Schirmer test results were significantly worse (ΔY: -11.47%±19.27). A significant difference between the 2 solutions was found in TBUT (ΔY: 13.98%±26.19 vs. 10.15%±42.34, respectively; P=0.0214). Visaid 0.3% is a safe product with some benefits over 0.9% NaCl in reducing ocular symptoms and improving some ocular signs in patients with moderate-to-severe dry eye.

Comparing the efficacy of xylitol-containing and conventional chewing gums in reducing salivary counts of Streptococcus mutans: An in vivo study

PubMed Central

Haghgoo, Rosa; Afshari, Elahe; Ghanaat, Tahere; Aghazadeh, Samaneh

2015-01-01

Objective: Dental caries is among the most common chronic diseases in humans. Streptococcus mutans is generally responsible for most cases of dental caries. The present study sought to compare the effects of xylitol-containing and conventional chewing gums on salivary levels of S. mutans. Materials and Methods: This study adopted a crossover design. Two type of chewing gums (one containing 70% xylitol and approved by the Iranian Dental Association, and another containing sucrose) were purchased. The participants were 32 individuals aged 18–35 years whose oral hygiene was categorized as moderate or poor based on a caries risk assessment table. Salivary levels of S. mutans were measured at baseline, after the first and second phases of chewing gums, and after the washout period. The measurements were performed on blood agar and mitis salivarius-bacitracin agar (MSBA). Pairwise comparisons were then used to analyze the collected data. Results: Salivary levels of S. mutans in both groups were significantly higher during the two stages of chewing gum than in the washout period or baseline. Moreover, comparisons between the two types of gums suggested that chewing xylitol-containing gums led to greater reductions in S. mutans counts. This effect was more apparent in subjects with poor oral hygiene than in those with moderate oral hygiene. Conclusions: Xylitol-containing chewing gums are more effective than conventional gums in reducing salivary levels of S. mutans in individuals with poor–moderate oral hygiene. PMID:26942114

Effect of drinking parsley leaf tea on urinary composition and urinary stones' risk factors.

PubMed

Alyami, Fahad A; Rabah, Danny M

2011-05-01

To investigate the effect of parsley leaf tea on urine composition and the inhibitors of urinary tract stones formation, we studied 20 healthy volunteers who were divided into two groups: the first group of 10 subjects drank daily 1,200 mL of parsley leaf tea for 2 weeks, while the second group drank at least 1,200 mL daily of bottled water for the same period. This was followed by a 2-week "washout" period before the two groups were crossed over for another 2 weeks. During the experimental phase, 24-h urine samples were collected at baseline, on day 14, and at the end of the 6-week period and different urinary parameters were measured and analyzed statistically. We found no significant difference in the urine volume, pH, sodium, potassium, chloride, urea, creatinine, phosphorus, magnesium, uric acid, cystine, or citric acid. Further research is needed to evaluate the effects of parsley leaf tea on urinary parameters in healthy and stone-forming patients.

Tradition and the individual sodomite: Barnfield, Shakespeare, and subjective desire.

PubMed

Bredbeck, G W

1992-01-01

This article compares Shakespeare's sonnets with those written by Richard Barnfield in order to examine the possibility of homoerotic subjectivity in early Renaissance England. Social constructionist debates about sexual subjectivity have convincingly argued that "the homosexual"--the person defined by homosexuality--did not exist before the Enlightenment. The sequences of Shakespeare and Barnfield, both of which deal with homoerotic desire, suggest that homoerotic desire could indeed play a role in defining the individuated subject prior to the Enlightenment. However, the ways in which they use homoeroticism also suggest that subjectivity was defined in radically different ways during the period.

Is the Sun a Long Period Variable

NASA Technical Reports Server (NTRS)

Sonett, Charles P.

1990-01-01

The inventory of atmospheric radiocarbon exhibits quasi-periodic variations of mean period of bar-lambda=269 years over the entire 9000 year record. But the period is inconstant and subject to random variability (sigma m exp. 1/2 = 119 years). The radiocarbon maxima correspond to the quasiperiodic extension of the Maunder minimum throughout the Holocene and resolve the long-standing issue of Maunder cyclicity. The radiocarbon maxima are amplitude modulated by the approx. 2300 year period and thus vary significantly in peak value. The approx. 2300 year period in turn appears to not be modulated by the secular geomagnetic variation. Detection of a Maunder-like sequence of minima in tree ring growth of Bristlecone pine and its correlation with the Maunder (1890, 1922) cyclicity in the radiocarbon record supports the inference that solar forcing of the radiocarbon record is accompanied by a corresponding forcing of growth of timberline Bristlecone pine. Because of the random component of the Maunder period, prediction of climate, if tied to the Maunder cycle other than probabilistically, is significantly hindered. For the mean Maunder period of 269 years, the probability is 67 percent that a given climatic maximum lies anywhere between 150 and 388 years.

Periodicity of extinction: A 1988 update

NASA Technical Reports Server (NTRS)

Sepkowski, J. John, Jr.

1988-01-01

The hypothesis that events of mass extinction recur periodically at approximately 26 my intervals is an empirical claim based on analysis of data from the fossil record. The hypothesis has become closely linked with catastrophism because several events in the periodic series are associated with evidence of extraterrestrial impacts, and terrestrial forcing mechanisms with long, periodic recurrences are not easily conceived. Astronomical mechanisms that have been hypothesized include undetected solar companions and solar oscillation about the galactic plane, which induce comet showers and result in impacts on Earth at regular intervals. Because these mechanisms are speculative, they have been the subject of considerable controversy, as has the hypothesis of periodicity of extinction. In response to criticisms and uncertainties, a data base was developed on times of extinction of marine animal genera. A time series is given and analyzed with 49 sample points for the per-genus extinction rate from the Late Permian to the Recent. An unexpected pattern in the data is the uniformity of magnitude of many of the periodic extinction events. Observations suggest that the sequence of extinction events might be the result of two sets of mechanisms: a periodic forcing that normally induces only moderate amounts of extinction, and independent incidents or catastrophes that, when coincident with the periodic forcing, amplify its signal and produce major-mass extinctions.

Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study.

PubMed

Udani, Jay K; Singh, Betsy B; Barrett, Marilyn L; Singh, Vijay J

2009-10-20

The ability to reduce inflammation in overweight and obese individuals may be valuable in preventing the progression to metabolic syndrome with associated risks for heart disease and diabetes. The purpose of this study was to evaluate the effect of multiple dosages of a proprietary Mangosteen Juice blend on indicators of inflammation and antioxidant levels in obese patients with elevated C-reactive protein (CRP) levels. The study was an 8 week randomized, double-blind, placebo-controlled study with a pre-study 2 week washout period. The study included four groups including placebo and three difference doses of the test product, XanGo Juice: 3, 6 or 9 oz twice daily. The primary outcome measure of this study was high-sensitivity (HS)-CRP. Secondary outcome measures included other biochemical indicators of inflammation, anthropomorphic measures and a safety evaluation. One hundred twenty two (122) persons were screened for the study, 44 were randomized and 40 completed the study. HS-CRP measurements dropped after 8 weeks treatment compared to baseline in all 3 dose groups and increased in the placebo group. The changes from baseline were not significant but the comparison of change from baseline was significant for the 18 oz group when compared to placebo (p = 0.02). Other markers of inflammation (inflammatory cytokines) and a marker for lipid peroxidation (F2 isoprostane) did not show any significant differences when compared with placebo. There was a trend towards a decrease in BMI in the juice groups. There were no side effects reported in any of the groups and none of the laboratory or EKG safety assessments indicated clinically significant changes for any subject. In this pilot, dose-finding study, a proprietary mangosteen juice blend (XanGo Juice) reduced CRP levels (increased change from baseline) compared to placebo for those taking the highest dose of 18 oz per day. Further studies with a larger population are required to confirm and further define the

Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study

PubMed Central

Udani, Jay K; Singh, Betsy B; Barrett, Marilyn L; Singh, Vijay J

2009-01-01

Background The ability to reduce inflammation in overweight and obese individuals may be valuable in preventing the progression to metabolic syndrome with associated risks for heart disease and diabetes. The purpose of this study was to evaluate the effect of multiple dosages of a proprietary Mangosteen Juice blend on indicators of inflammation and antioxidant levels in obese patients with elevated C-reactive protein (CRP) levels. Methods The study was an 8 week randomized, double-blind, placebo-controlled study with a pre-study 2 week washout period. The study included four groups including placebo and three difference doses of the test product, XanGo Juice™: 3, 6 or 9 oz twice daily. The primary outcome measure of this study was high-sensitivity (HS)-CRP. Secondary outcome measures included other biochemical indicators of inflammation, anthropomorphic measures and a safety evaluation. Results One hundred twenty two (122) persons were screened for the study, 44 were randomized and 40 completed the study. HS-CRP measurements dropped after 8 weeks treatment compared to baseline in all 3 dose groups and increased in the placebo group. The changes from baseline were not significant but the comparison of change from baseline was significant for the 18 oz group when compared to placebo (p = 0.02). Other markers of inflammation (inflammatory cytokines) and a marker for lipid peroxidation (F2 isoprostane) did not show any significant differences when compared with placebo. There was a trend towards a decrease in BMI in the juice groups. There were no side effects reported in any of the groups and none of the laboratory or EKG safety assessments indicated clinically significant changes for any subject. Conclusion In this pilot, dose-finding study, a proprietary mangosteen juice blend (XanGo Juice™) reduced CRP levels (increased change from baseline) compared to placebo for those taking the highest dose of 18 oz per day. Further studies with a larger population are

Changes in plasma and oral mucosal lycopene isomer concentrations in healthy adults consuming standard servings of processed tomato products.

PubMed

Allen, Charlotte M; Schwartz, Steven J; Craft, Neal E; Giovannucci, Edward L; De Groff, Valerie L; Clinton, Steven K

2003-01-01

The consumption of tomato products is associated with a reduced risk of cardiovascular disease and several cancers. It is hypothesized that lycopene, the major carotenoid in tomato products, may mediate this relationship. We designed a study to examine changes in plasma and buccal mucosal cell (BMC) lycopene concentrations in healthy adults consuming standard daily servings of processed tomato products: spaghetti sauce, tomato soup, or vegetable juice. Thirty-six healthy subjects consumed a lycopene-free diet for 2 wk and were then assigned to one of three (n = 12) intervention groups consuming daily, single servings of sauce (21 mg lycopene per (1/2) cup), soup (12 mg lycopene per 1 cup), or juice (17 mg lycopene per 8 oz) for 4 wk. Fasting blood and BMC samples were evaluated by high-performance liquid chromatography analysis for carotenoids and lycopene isomers. Total plasma lycopene concentrations (Mean +/- SEM) decreased from 1.05 +/- 0.07 to 0.54 +/- 0.05 micromol/l (49%, P < 0.0001) during the 2-wk washout period. Following intervention, plasma lycopene concentrations increased significantly for those consuming sauce, soup, and juice (compared with washout baseline) to 2.08 (192%, P < 0.0001), 0.91 (122%, P < 0.0001), and 0.99 (92%, P < 0.0001) micromol/l, respectively. Plasma isomer concentrations show a 61:39 ratio of cis:all-trans at the start of the study. During the 2-wk washout the decrease in plasma all-trans-lycopene was greater than that for pooled cis isomers (70:30 cis:trans ratio, P < 0.001). After 2 wk of dietary intervention isomer ratios returned to those observed at the start of the study. Total BMC lycopene concentrations did not significantly change during the brief washout. During the 4-wk intervention period, BMC total lycopene concentrations increased (P < 0.005) by 165, 42, and 48% nmol/mg protein for those consuming sauce, soup, and juice, respectively. This study demonstrates that plasma lycopene decreases by 50% after approximately 2

49 CFR 452.1 - Periodic examination required.

Code of Federal Regulations, 2013 CFR

2013-10-01

... SECURITY SAFETY APPROVAL OF CARGO CONTAINERS EXAMINATION OF CONTAINERS § 452.1 Periodic examination required. (a) Except as provided for in § 452.7, each owner of an approved container subject to this part shall examine the container or have it examined in accordance with the procedures prescribed in § 452.3...

49 CFR 452.1 - Periodic examination required.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SECURITY SAFETY APPROVAL OF CARGO CONTAINERS EXAMINATION OF CONTAINERS § 452.1 Periodic examination required. (a) Except as provided for in § 452.7, each owner of an approved container subject to this part shall examine the container or have it examined in accordance with the procedures prescribed in § 452.3...

49 CFR 452.1 - Periodic examination required.

Code of Federal Regulations, 2012 CFR

2012-10-01

... SECURITY SAFETY APPROVAL OF CARGO CONTAINERS EXAMINATION OF CONTAINERS § 452.1 Periodic examination required. (a) Except as provided for in § 452.7, each owner of an approved container subject to this part shall examine the container or have it examined in accordance with the procedures prescribed in § 452.3...

49 CFR 452.1 - Periodic examination required.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SECURITY SAFETY APPROVAL OF CARGO CONTAINERS EXAMINATION OF CONTAINERS § 452.1 Periodic examination required. (a) Except as provided for in § 452.7, each owner of an approved container subject to this part shall examine the container or have it examined in accordance with the procedures prescribed in § 452.3...

49 CFR 452.1 - Periodic examination required.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SECURITY SAFETY APPROVAL OF CARGO CONTAINERS EXAMINATION OF CONTAINERS § 452.1 Periodic examination required. (a) Except as provided for in § 452.7, each owner of an approved container subject to this part shall examine the container or have it examined in accordance with the procedures prescribed in § 452.3...

Washout of water-soluble vitamins and of homocysteine during haemodialysis: effect of high-flux and low-flux dialyser membranes.

PubMed

Heinz, Judith; Domröse, Ute; Westphal, Sabine; Luley, Claus; Neumann, Klaus H; Dierkes, Jutta

2008-10-01

Vitamin deficiencies are common in patients with end-stage renal disease (ESRD) owing to dietary restrictions, drug-nutrient interactions, changes in metabolism, and vitamin losses during dialysis. The present study investigated the levels of serum and red blood cell (RBC) folate, plasma pyridoxal-5'-phosphate (PLP), serum cobalamin, blood thiamine, blood riboflavin, and plasma homocysteine (tHcy) before and after haemodialysis treatment. Vitamin and tHcy blood concentrations were measured in 30 patients with ESRD before and after dialysis session either with low-flux (n = 15) or high-flux (n = 15) dialysers. After the dialysis procedure, significantly lower concentrations of serum folate (37%), plasma PLP (35%), blood thiamine (6%) and blood riboflavin (7%) were observed. No significant changes were found for serum cobalamin or for RBC folate. There were no differences in the washout of water-soluble vitamins between treatments with low-flux and high-flux membranes. Furthermore, a 41% lower concentration in tHcy was observed. The percentage decrease in tHcy was significantly greater in the patients treated with high-flux dialysers (48% vs 37%; P < 0.01). The percentage change during dialysis was significantly inversely related to the molecular weight of the vitamins measured (r =-0.867, P < 0.01). This study showed significantly lower blood or serum levels of various water-soluble vitamins after dialysis, independently of the dialyser membrane. The monitoring of the vitamin status is essential in patients treated with high-flux dialysers as well as in patients treated with low-flux dialysers.

An Analysis of Japanese Medical Periodicals

PubMed Central

Taniguchi, Mayumi

1965-01-01

Medical periodicals published in Japan were studied by analyzing the journals abstracted in Igaku Chuo Zasshi (ICZ), the most comprehensive abstracting service for Japanese medical journal articles. Since the inauguration of medical periodicals in 1869, the number of journals has increased remarkably. In 1963 ICZ abstracted 1,074 journals published in Japan (960 in Japanese and 114 in other languages). Of these 1,074 titles, 855 were on medical sciences, of which 740 were substantive. A subject analysis of the substantive journals in ICZ, as compared to the 124 Japanese journals currently indexed in Index Medicus, was also made. Data were presented relating the number of periodicals to the size of the medical scene in Japan and the United States, and it was pointed out that good control of the literature, by whatever methods, requires a knowledge of the extent of the publications. PMID:14223738

Cells anticipate periodic events

NASA Astrophysics Data System (ADS)

Nakagaki, Toshiyuki

2009-03-01

We show that an amoeboid organism can anticipate the timing of periodic events. The plasmodium of the true slime mold Physarum polycephalum moves rapidly under favourable conditions, but stops moving when transferred to less-favourable conditions. Plasmodia exposed to unfavourable conditions, presented in three consecutive pulses at constant intervals, reduced their locomotive speed in response to each episode. When subsequently subjected to favourable conditions, the plasmodia spontaneously reduced their locomotive speed at the time point when the next unfavourable episode would have occurred. This implied anticipation of impending environmental change. After this behaviour had been evoked several times, the locomotion of the plasmodia returned to normal; however, the anticipatory response could subsequently be induced by a single unfavourable pulse, implying recall of the memorized periodicity. We explored the mechanisms underlying these behaviours from a dynamical systems perspective. Our results hint at the cellular origins of primitive intelligence and imply that simple dynamics might be sufficient to explain its emergence.

[Behavioral reactions of animals subjected in the prenatal development period to space flight conditions].

PubMed

Apanasenko, Z I; Kuznetsova, M A; Korotkova, V Iu

1986-01-01

The Wistar female rats were flown on the biosatellite Cosmos-1514 during their pregnancy days 13-18. Offspring (at the age 1 to 3 months) of four of these rats were used to investigate their behavioral reactions in the open field and mazes of different design, food attraction being applied. Control rats of matched pregnancy term were kept either in a vivarium or in a biosatellite mockup where all flight factors, except for weightlessness, were simulated. It was found that exposure to weightlessness in the above intrauterine developmental period caused no serious changes in the behavioral reactions of rats during their postnatal development. The number of refusals and errors and the latency period were similar in the rats from the flight and control groups. Changes were seen only in fine behavioral regulation. The flown animals displayed a lower research activity in the open field, a longer time of search in the maze, a far longer time or grooming and a greater number of inadequate movements, and a stronger response to external inhibiting stimuli. These changes seem to be caused by a slight attenuation of the basic nervous processes (primarily, inhibitory) and a decrease of their balance and lability. These effects may be associated with an inhibitory influence of space flight factors on the maturation of cortical structures.

Pharmacokinetics of the B-Cell Lymphoma 2 (Bcl-2) Inhibitor Venetoclax in Female Subjects with Systemic Lupus Erythematosus.

PubMed

Minocha, Mukul; Zeng, Jiewei; Medema, Jeroen K; Othman, Ahmed A

2018-01-15

Venetoclax is an oral selective Bcl-2 inhibitor approved for the treatment of patients with chronic lymphocytic leukemia with 17p deletion. Mechanistic and preclinical evidence warranted evaluation of venetoclax for the treatment of systemic lupus erythematosus (SLE). This work characterized the pharmacokinetics of venetoclax in female subjects with SLE. Single (10-500 mg) and multiple (30-600 mg) escalating doses of venetoclax or matching placebo were evaluated using randomized, double-blind, placebo-controlled designs (6 active and 2 placebo per dose with 73 unique SLE patients enrolled, 25 of whom enrolled twice). The multiple-dose evaluation consisted of two cycles, each with once-daily dosing for 7 days followed by a 21-day washout. Non-compartmental and population pharmacokinetic analyses of venetoclax serial plasma concentrations were conducted. Venetoclax exhibited approximately dose-proportional exposures, with peak concentrations observed 4-8 h post-dose. Venetoclax steady-state exposures were achieved by day 4 of dosing, and the median area under the plasma concentration-time curve (AUC) accumulation ratio ranged from 1.1 to 1.5. A two-compartment model with first-order absorption and elimination described venetoclax pharmacokinetics. The estimates (95% bootstrap confidence interval) for venetoclax apparent clearance, central and peripheral volumes of distribution, intercompartmental clearance, absorption rate constant, and lag time were 16.3 L/h (14.6-17.9), 37 L (26-57), 122 L (98-183), 3.7 L/h (2.6-5.0), 0.13 h -1 (0.11-0.17), and 1.6 h (1.6-1.7), respectively. The population estimate for venetoclax terminal-phase elimination half-life was approximately 28 h. In female subjects with SLE, venetoclax displayed pharmacokinetic characteristics consistent with previous observations in subjects with hematologic malignancies. CLINICALTRIALS. NCT01686555.

Effect of Muscadine Grape Seed Supplementation on Vascular Function in Subjects with or at Risk for Cardiovascular Disease: A Randomized Crossover Trial

PubMed Central

Mellen, Philip B.; Daniel, Kurt R.; Brosnihan, K. Bridget; Hansen, Kim J.; Herrington, David M.

2012-01-01

Background Muscadine grape seeds have high concentrations of polyphenolic compounds with antioxidant and other properties that would be expected to have favorable effects on endothelial function. Objectives To evaluate the effect of muscadine grape seed supplementation on endothelial function and cardiovascular risk factors in subjects with increased cardiovascular risk. Design In a randomized, double-blind, placebo-controlled crossover trial, 50 adults with coronary disease or ≥1 cardiac risk factor received muscadine grape seed supplementation (1300 mg daily) and placebo for 4 weeks each, with a 4-week washout. Resting brachial diameter and brachial flow-mediated dilation (FMD) and biomarkers of inflammation, lipid peroxidation, and antioxidant capacity were determined at the beginning and end of each period and compared in mixed linear models. Results There was no evidence of improved FMD (% change) with muscadine grape seed (muscadine grape seed: pre 5.2% ± 0.3%, post 4.6% ± 0.3%, p = 0.06; placebo: pre 5.3% ± 0.4%, post 5.2% ± 0.4%, p = 0.82; p for muscadine grape seed vs. placebo = 0.25). However, there was a significant increase in baseline diameter (mm) with muscadine grape seed supplementation (muscadine grape seed: pre 4.05 ± 0.09, post 4.23 ± 0.10, p = 0.002; placebo: pre 4.12 ± 0.11, post 4.12 ± 0.10, p = 0.93; p for muscadine grape seed vs. placebo = 0.026). All other biomarkers were not significantly altered by muscadine grape seed supplementation. Conclusions Four weeks of muscadine grape seed supplementation in subjects with increased cardiovascular risk did not produce a statistically significant increase in brachial flow-mediated vasodilation or a significant change in other biomarkers of inflammation, lipid peroxidation, or antioxidant capacity. However, the muscadine grape seed supplement did result in a significant increase in resting brachial diameter. The clinical significance of the effect on resting diameter is not yet established

Pharmacokinetics and bioequivalence evaluation of two different atorvastatin calcium 10-mg tablets: A single-dose, randomized-sequence, open-label, two-period crossover study in healthy fasted Chinese adult males.

PubMed

Liu, Yan-Mei; Pu, Hua-Hua; Liu, Gang-Yi; Jia, Jing-Ying; Weng, Li-Ping; Xu, Rong-Jing; Li, Guo-Xiu; Wang, Wei; Zhang, Meng-Qi; Lu, Chuan; Yu, Chen

2010-07-01

Atorvastatin calcium is a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor indicated for the prevention of cardiovascular disease and for the treatment of dyslipidemia. Information on the pharmacokinetics of atorvastatin in a Chinese population is lacking, and regulatory requirements necessitate a bioequivalence study for the marketing of a generic product in China. The aim of the present study was to assess the pharmacokinetics and bioequivalence of a test and branded reference formulation of atorvastatin calcium 10-mg tablets in healthy fasted Chinese male volunteers. This was a single-dose, randomized-sequence, open-label, 2-period crossover study with a 2-week washout period between doses. Healthy Chinese males were randomly assigned to receive 20 mg of either the test or reference formulation, and 13 blood samples were obtained over a 48-hour interval. Plasma concentrations of parent atorvastatin and ortho-hydroxy-atorvastatin (primary active metabolite) were simultaneously determined using a validated liquid chromatography-isotopic dilution mass spectrometry method. Pharmacokinetic parameters, including C(max), T(max), t((1/2)), AUC(0-t), and AUC(0-infinity)), were calculated. The 2 formulations were to be considered bioequivalent if 90% CIs for the log transformed ratios of AUC and C(max) of atorvastatin were within the predetermined bioequivalence range (0.80-1.25 for AUC and 0.70-1.43 for C(max)) as established by the State Food and Drug Administration of China. Tolerability was evaluated throughout the study by vital signs monitoring, physical examinations, 12-lead ECGs, and subject interviews on adverse events (AEs). A total of 66 subjects were assessed for inclusion; 20 were excluded prior to study initiation. Of the 46 healthy subjects (mean [SD] age, 24.1 [2.5] years; height, 170.8 [5.1] cm; weight, 64.6 [6.4] kg; body mass index (BMI), 22.1 [1.7] kg/m(2)) who completed the study, 45 subjects (mean [SD] age, 24.1 [2.5] years; height, 171.1 [4

Distribution of 10 periodontal bacterial species in children and adolescents over a 7-year period.

PubMed

Nakano, K; Miyamoto, E; Tamura, K; Nemoto, H; Fujita, K; Nomura, R; Ooshima, T

2008-10-01

There is scant information available regarding the distribution of periodontal bacterial species in children and adolescents over an extended period. The purpose of this study was to compare bacterial profiles in the same individuals over a period of 7 years. Twenty-six children and adolescents from whom dental plaque and saliva specimens were obtained during both the first (1999-2000) and second (2006-2007) periods, were analyzed. Bacterial DNA was extracted from each specimen and the presence of 10 periodontal bacterial species was determined using a PCR method, with a focus on the red complex species of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. Subjects with red complex species in saliva specimens obtained during the second collection possessed a significantly higher number of total bacterial species than those without. The detection rate of the red complex species in the second collection period samples was significantly greater in subjects who had two or more species detected in samples taken during the first collection compared with the other subjects. Subjects possessing red complex species may be at possible risk for infection with a high number of periodontal bacterial species during adolescent and younger adult years.

The effect of vacuum devices on penile hemodynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katz, P.G.; Haden, H.T.; Mulligan, T.

1990-01-01

External vacuum devices are being used increasingly for the management of erectile dysfunction. There is limited information regarding the effect of vacuum devices on penile blood flow and potential for ischemic penile injury. The penile xenon washout rate was measured before and after application of 2 vacuum systems in 15 subjects. Compared to flaccid state measurements the xenon washout rate did not change significantly with the Synergist Erection System but it was significantly reduced with the Osbon ErecAid System. However, the degree and duration of decrease in penile blood flow that may result in ischemic changes are unknown.

Violence and Death in Stories of War Period Writer Omer Seyfettin

ERIC Educational Resources Information Center

Turan, Lokman

2006-01-01

In this article, a brief biography is given and information is provided on, the period Omer Seyfettin, one of the most widely read children's literature writers in Turkey lived in, and the subject of death and violence in 129 short stories he has written, compiled in 10 books, was analyzed. The data was subjected to computer aided quantitative…

A hybrid multibreath wash-in wash-out lung function quantification scheme in human subjects using hyperpolarized 3 He MRI for simultaneous assessment of specific ventilation, alveolar oxygen tension, oxygen uptake, and air trapping.

PubMed

Hamedani, Hooman; Kadlecek, Stephen; Xin, Yi; Siddiqui, Sarmad; Gatens, Heather; Naji, Joseph; Ishii, Masaru; Cereda, Maurizio; Rossman, Milton; Rizi, Rahim

2017-08-01

To present a method for simultaneous acquisition of alveolar oxygen tension (P A O 2 ), specific ventilation (SV), and apparent diffusion coefficient (ADC) of hyperpolarized (HP) gas in the human lung, allowing reinterpretation of the P A O 2 and SV maps to produce a map of oxygen uptake (R). An imaging scheme was designed with a series of identical normoxic HP gas wash-in breaths to measure ADC, SV, P A O 2 , and R in less than 2 min. Signal dynamics were fit to an iterative recursive model that regionally solved for these parameters. This measurement was successfully performed in 12 subjects classified in three healthy, smoker, and chronic obstructive pulmonary disease (COPD) cohorts. The overall whole lung ADC, SV, P A O 2 , and R in healthy, smoker, and COPD subjects was 0.20 ± 0.03 cm 2 /s, 0.39 ± 0.06,113 ± 2 Torr, and 1.55 ± 0.35 Torr/s, respectively, in healthy subjects; 0.21 ± 0.03 cm 2 /s, 0.33 ± 0.06, 115.9 ± 4 Torr, and 0.97 ± 0.2 Torr/s, respectively, in smokers; and 0.25 ± 0.06 cm 2 /s, 0.23 ± 0.08, 114.8 ± 6.0Torr, and 0.94 ± 0.12 Torr/s, respectively, in subjects with COPD. Hetrogeneity of SV, P A O 2 , and R were indicators of both smoking-related changes and disease, and the severity of the disease correlated with the degree of this heterogeneity. Subjects with symptoms showed reduced oxygen uptake and specific ventilation. High-resolution, nearly coregistered and quantitative measures of lung function and structure were obtained with less than 1 L of HP gas. This hybrid multibreath technique produced measures of lung function that revealed clear differences among the cohorts and subjects and were confirmed by correlations with global lung measurements. Magn Reson Med 78:611-624, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Mechanical instabilities in periodic porous elasto-plastic solids.

NASA Astrophysics Data System (ADS)

Singamaneni, Srikanth; Bertoldi, Katia; Chang, Sehoon; Jang, Ji-Hyun; Young, Seth; Thomas, Edwin; Boyce, Mary; Tsukruk, Vladimir

2009-03-01

We describe the transformation of the periodic microporous structures fabricated by interference lithography followed by their freezing below glass transition. Periodic porous microstructures subjected to internal compressive stresses can undergo sudden structural transformation at a critical strain. The pattern transformation of collapsed pores is caused by the stresses originated during the polymerization of acrylic acid (rubbery component) inside of cylindrical pores and the subsequent solvent evaporation in the organized microporous structure. The results of a non-linear numerical investigation confirm the critical role of the bifurcation of the periodic solid under compressive stresses. In striking contrast to the earlier observations of elastic instabilities in porous elastomeric solids, the elastic-plastic nature of the crosslinked periodic microstructure studied here provides for the ability to lock in the transformed pattern with complete relaxation of the internal stresses. By confining the polymerization of acrylic acid to localized porous areas complex microscopic periodic structures are obtained.

Clinical comparison of a new manual toothbrush on breath volatile sulfur compounds.

PubMed

Williams, Malcolm I; Vazquez, Joe; Cummins, Diane

2004-10-01

The objective of this randomized, crossover study was to compare the effectiveness of a newly designed manual toothbrush (Colgate 360 degrees) to two commercially available manual toothbrushes (Oral-B Indicator and Oral-B CrossAction) and a battery-powered toothbrush (Crest SpinBrush PRO) for their ability to reduce overnight volatile sulfur compounds (VSC) associated with oral malodor. The study followed a four-period crossover design. Following a washout period, prospective subjects arrived at the testing facility without eating, drinking, or performing oral hygiene for baseline evaluation of breath VSC levels. For each phase of the study, subjects were given one of the test tooth-brushes and a tube of regular toothpaste to take home, and they were instructed to brush their teeth in their customary manner for 1 minute. When using the Colgate 360 degrees toothbrush, subjects were instructed to clean their tongue with the implement on the back of the brush head for 10 seconds. The following morning, subjects reported to the testing facility, again without performing oral hygiene, eating, or drinking, for the overnight evaluation. After a minimum 2-day washout period, subjects repeated the same regimen using the other toothbrushes. The levels of breath VSC were evaluated instrumentally using a gas chromatograph equipped with a flame photometric detector. Measurements were taken in duplicate and then averaged. The levels of VSC were expressed as parts per billion (ppb) in mouth air. Sixteen men and women completed the study. At baseline, the mean levels of VSC in mouth air for the 4 toothbrushes were 719.8 ppb+/-318.4 ppb, 592.8 ppb+/-264.6 ppb, 673.8 ppb+/-405.9 ppb, and 656.2 ppb+/-310.2 ppb for the Colgate 360 degrees, Oral-B Indicator, Crest SpinBrush PRO, and Oral-B CrossAction, respectively. Overnight, the mean breath VSC levels after using the four toothbrushes were lower than those observed at baseline. The respective mean levels of breath VSC were 266.5 ppb

Existence of time-periodic weak solutions to the stochastic Navier-Stokes equations around a moving body

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Feng, E-mail: chenfengmath@163.com, E-mail: hanyc@jlu.edu.cn; Han, Yuecai, E-mail: chenfengmath@163.com, E-mail: hanyc@jlu.edu.cn

2013-12-15

The existence of time-periodic stochastic motions of an incompressible fluid is obtained. Here the fluid is subject to a time-periodic body force and an additional time-periodic stochastic force that is produced by a rigid body moves periodically stochastically with the same period in the fluid.

Multimedia Based on Scientific Approach for Periodic System of Element

NASA Astrophysics Data System (ADS)

Sari, S.; Aryana, D. M.; Subarkah, C. Z.; Ramdhani, M. A.

2018-01-01

This study aims to describe the application of interactive multimedia on the concept of the periodic system of elements. The study was conducted by using the one-shot case study design. The subjects in this study were 35 high school students of class XI IPA. Results showed that the stages of observing, questioning, data collecting (experimenting), and communicating are all considered very good. This shows that multimedia can assist students in explaining the development of the periodic system of elements, ranging from Triade doberrainer, Newland Octarchic Law, Mendeleyev, and the modern periodic, as well as atomic radius, ionization energy, and electronegativity of an element in the periodic system.

Angiotensin-converting enzyme inhibition improves cardiac fatty acid metabolism in patients with congestive heart failure.

PubMed

Yamauchi, S; Takeishi, Y; Minamihaba, O; Arimoto, T; Hirono, O; Takahashi, H; Miyamoto, T; Nitobe, J; Nozaki, N; Tachibana, H; Watanabe, T; Fukui, A; Kubota, I

2003-08-01

This study aimed to examine whether angiotensin-converting enzyme (ACE) inhibition improved cardiac fatty acid metabolism in patients with congestive heart failure (CHF). Myocardial 123I-beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP) imaging was performed in 25 patients with CHF and in 10 control subjects. Myocardial 123I-BMIPP images were obtained 30 min and 4 h after tracer injection. The heart-to-mediastinum (H/M) ratio of 123I-BMIPP uptake and the washout rate of 123I-BMIPP from the myocardium were calculated. Patients were given enalapril for 6 months, and 123I-BMIPP imaging was repeated. H/M ratios on early and delayed images were lower in CHF patients than in normal controls (P<0.01). The washout rate of 123I-BMIPP from the myocardium was faster in CHF patients than in controls (P<0.01). As the severity of the New York Heart Association (NYHA) functional class increased, the H/M ratio decreased and the washout rate increased. The washout rate of 123I-BMIPP was inversely correlated with left ventricular fractional shortening (R=-0.62, P<0.01). ACE inhibition with enalapril increased the H/M ratio on delayed images (P<0.05) and reduced the washout rate of 123I-BMIPP (P<0.05) in CHF patients. These data suggest that: (1) angiotensin II-mediated intracellular signalling activation may be a possible mechanism for the decreased myocardial uptake and enhanced washout of 123I-BMIPP in heart failure patients; and (2) the improvement in fatty acid metabolism by ACE inhibition may represent a new mechanism for the beneficial effect of this therapy in heart failure.

Assessment of inflow and washout of indocyanine green in the adult human brain by monitoring of diffuse reflectance at large source-detector separation

NASA Astrophysics Data System (ADS)

Liebert, Adam; Sawosz, Piotr; Milej, Daniel; Kacprzak, Michał; Weigl, Wojciech; Botwicz, Marcin; MaCzewska, Joanna; Fronczewska, Katarzyna; Mayzner-Zawadzka, Ewa; Królicki, Leszek; Maniewski, Roman

2011-04-01

Recently, it was shown in measurements carried out on humans that time-resolved near-infrared reflectometry and fluorescence spectroscopy may allow for discrimination of information originating directly from the brain avoiding influence of contaminating signals related to the perfusion of extracerebral tissues. We report on continuation of these studies, showing that the near-infrared light can be detected noninvasively on the surface of the tissue at large interoptode distance. A multichannel time-resolved optical monitoring system was constructed for measurements of diffuse reflectance in optically turbid medium at very large source-detector separation up to 9 cm. The instrument was applied during intravenous injection of indocyanine green and the distributions of times of flight of photons were successfully acquired showing inflow and washout of the dye in the tissue. Time courses of the statistical moments of distributions of times of flight of photons are presented and compared to the results obtained simultaneously at shorter source-detector separations (3, 4, and 5 cm). We show in a series of experiments carried out on physical phantom and healthy volunteers that the time-resolved data acquisition in combination with very large source-detector separation may allow one to improve depth selectivity of perfusion assessment in the brain.

Food increases the bioavailability of isotretinoin.

PubMed

Colburn, W A; Gibson, D M; Wiens, R E; Hanigan, J J

1983-01-01

Twenty healthy male subjects received 80 mg (2 X 40 mg SEG capsules) oral isotretinoin separated by two-week washout periods in an open randomized crossover design. Isotretinoin was administered during a complete fast, 1 hour after a standard breakfast, with a standard breakfast, or 1 hour before a standard breakfast. Blood samples were obtained at specific times over a 72-hour period. Isotretinoin blood concentrations were determined by a specific HPLC method. The relative bioavailability (AUC) of isotretinoin was found to be approximately 1.5 to 2 times greater when the dose was administered 1 hour before, concomitantly with, or 1 hour after a meal than when it was given during a complete fast. In addition, because the Cmax value is lower when the dose is administered with food rather than 1 hour after a meal, coadministration of isotretinoin with food may be the best method of administration.

Physiological Responses to Two Hypoxic Conditioning Strategies in Healthy Subjects

PubMed Central

Chacaroun, Samarmar; Borowik, Anna; Morrison, Shawnda A.; Baillieul, Sébastien; Flore, Patrice; Doutreleau, Stéphane; Verges, Samuel

2017-01-01

Objective: Hypoxic exposure can be used as a therapeutic tool by inducing various cardiovascular, neuromuscular, and metabolic adaptations. Hypoxic conditioning strategies have been evaluated in patients with chronic diseases using either sustained (SH) or intermittent (IH) hypoxic sessions. Whether hypoxic conditioning via SH or IH may induce different physiological responses remains to be elucidated. Methods: Fourteen healthy active subjects (7 females, age 25 ± 8 years, body mass index 21.5 ± 2.5 kg·m−2) performed two interventions in a single blind, randomized cross-over design, starting with either 3 x SH (48 h apart), or 3 x IH (48 h apart), separated by a 2 week washout period. SH sessions consisted of breathing a gas mixture with reduced inspiratory oxygen fraction (FiO2), continuously adjusted to reach arterial oxygen saturations (SpO2) of 70–80% for 1 h. IH sessions consisted of 5 min with reduced FiO2 (SpO2 = 70–80%), followed by 3-min normoxia, repeated seven times. During the first (S1) and third (S3) sessions of each hypoxic intervention, cardiorespiratory parameters, and muscle and pre-frontal cortex oxygenation (near infrared spectroscopy) were assessed continuously. Results: Minute ventilation increased significantly during IH sessions (+2 ± 2 L·min−1) while heart rate increased during both SH (+11 ± 4 bpm) and IH (+13 ± 5 bpm) sessions. Arterial blood pressure increased during all hypoxic sessions, although baseline normoxic systolic blood pressure was reduced from S1 to S3 in IH only (−8 ± 11 mmHg). Muscle oxygenation decreased significantly during S3 but not S1, for both hypoxic interventions (S3: SH −6 ± 5%, IH −3 ± 4%); pre-frontal oxygenation decreased in S1 and S3, and to a greater extent in SH vs. IH (−13 ± 3% vs. −6 ± 6%). Heart rate variability indices indicated a significantly larger increase in sympathetic activity in SH vs. IH (lower SDNN, PNN50, and RMSSD values in SH). From S1 to S3, further reduction in

Sleep, daily activity rhythms and postpartum mood: A longitudinal study across the perinatal period.

PubMed

Krawczak, Elizabeth M; Minuzzi, Luciano; Simpson, William; Hidalgo, Maria Paz; Frey, Benicio N

2016-01-01

Women with a diagnosis of bipolar and major depressive disorders are at higher risk to develop postpartum depression. The primary objective of this longitudinal study was to determine whether daily activity rhythms and sleep parameters differ between women with and without a history of a mood disorder across the perinatal period. A secondary objective was to determine whether changes in these parameters were associated with postpartum mood. In total, 33 women were included in this study, 15 of which had a history of a mood disorder (high-risk group) and 18 who did not (low-risk group). Sleep and daily rhythms were assessed subjectively and objectively during the third trimester (≥26 weeks gestation) and again at 6-12 weeks postpartum. Mood was also assessed at both time points. Women in the high-risk group showed greater subjective daily rhythms and sleep disturbances across the perinatal period. Objective sleep efficiency was worse in the high-risk group in the postpartum period. Changes in both subjective daily rhythms and objective sleep efficiency were predictive of changes in depressive symptoms across the perinatal period. These findings encourage the development of preventative therapeutics to ensure circadian rhythm and sleep stability throughout the perinatal period.

The neural networks of subjectively evaluated emotional conflicts.

PubMed

Rohr, Christiane S; Villringer, Arno; Solms-Baruth, Carolina; van der Meer, Elke; Margulies, Daniel S; Okon-Singer, Hadas

2016-06-01

Previous work on the neural underpinnings of emotional conflict processing has largely focused on designs that instruct participants to ignore a distracter which conflicts with a target. In contrast, this study investigated the noninstructed experience and evaluation of an emotional conflict, where positive or negative cues can be subjectively prioritized. To this end, healthy participants freely watched short film scenes that evoked emotional conflicts while their BOLD responses were measured. Participants' individual ratings of conflict and valence perception during the film scenes were collected immediately afterwards, and the individual ratings were regressed against the BOLD data. Our analyses revealed that (a) amygdala and medial prefrontal cortex were significantly involved in prioritizing positive or negative cues, but not in subjective evaluations of conflict per se, and (b) superior temporal sulcus (STS) and inferior parietal lobule (IPL), which have been implicated in social cognition and emotion control, were involved in both prioritizing positive or negative cues and subjectively evaluating conflict, and may thus constitute "hubs" or "switches" in emotional conflict processing. Psychophysiological interaction (PPI) analyses further revealed stronger functional connectivity between IPL and ventral prefrontal-medial parietal areas in prioritizing negative cues, and stronger connectivity between STS and dorsal-rostral prefrontal-medial parietal areas in prioritizing positive cues. In sum, our results suggest that IPL and STS are important in the subjective evaluation of complex conflicts and influence valence prioritization via prefrontal and parietal control centers. Hum Brain Mapp 37:2234-2246, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study

PubMed Central

Choi, YoonJung; Lee, SeungHwan; Cho, Sang-Min; Kang, Won-Ho; Nam, Kyu-Yeol; Jang, In-Jin; Yu, Kyung-Sang

2016-01-01

Background A fixed-dose combination (FDC) of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects. Subjects and methods A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography–tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs) of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax) and the area under the concentration curve from time zero to the last quantifiable time point (AUC0–t) were estimated. Tolerability assessments were performed for all subjects who received the drug at least once. Results The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0–t were 0.98 (0.94−1.01) and 0.97 (0.93−1.01), respectively. The corresponding values for losartan were 0.91 (0.81−1.02) and 1.05 (0.98−1.12), respectively. The incidence of adverse events was not significantly different between the two treatments, and both were well tolerated. Conclusion An FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK parameters of amlodipine and losartan based on Cmax and AUC0–t values. The amlodipine besylate

Internal jugular vein blood flow in multiple sclerosis patients and matched controls.

PubMed

Mancini, Marcello; Lanzillo, Roberta; Liuzzi, Raffaele; Di Donato, Orlando; Ragucci, Monica; Monti, Serena; Salvatore, Elena; Morra, Vincenzo Brescia; Salvatore, Marco

2014-01-01

The aim of the study was to investigate the Internal Jugular Veins dynamics using contrast enhanced ultrasonography in Multiple Sclerosis patients, clinically isolated syndrome patients and healthy controls. Contrast enhanced ultrasonography imaging of the Internal Jugular Vein was performed in fifty-eight patients with Multiple Sclerosis, seven clinically isolated syndrome patients and in thirteen healthy controls. Time-intensity curves were quantified using a semi-automated method and compared with clinical disease outcomes. Wash-out parameters were calculated and six Time-intensity curves shapes were created. Significantly reduction of wash-out rate in Internal Jugular Veins was detected in Multiple Sclerosis patients compared to healthy controls [22.2% (2.7%-65.9%) vs. 33.4% (16.2%-76.8%); P<0.005]. Internal Jugular Vein enhancement was heterogeneous in patients with Multiple Sclerosis and consisted of slow wash-out Time-intensity curves shapes, compared with almost only one type of Time-intensity curves shape in control subjects that correspond to fast enhancement and fast wash-out. The vein wash-in parameters were similar in Multiple Sclerosis group compared with controls. A significant correlation was found between Internal Jugular Vein wash-out and level of disability (R =  -0.402, p<0.05). Contrast enhanced ultrasonography of the Internal Jugular Vein with time intensity curve analysis revealed alterations of cerebral venous outflow in Multiple Sclerosis patients, however mechanisms that determine this condition remains unclear.

Single-dose pharmacokinetics of co-crystal of tramadol-celecoxib: Results of a four-way randomized open-label phase I clinical trial in healthy subjects.

PubMed

Videla, Sebastián; Lahjou, Mounia; Vaqué, Anna; Sust, Mariano; Encabo, Mercedes; Soler, Lluis; Sans, Artur; Sicard, Eric; Gascón, Neus; Encina, Gregorio; Plata-Salamán, Carlos

2017-12-01

Co-crystal of tramadol-celecoxib (CTC) is a novel co-crystal molecule containing two active pharmaceutical ingredients under development by Esteve (E-58425) and Mundipharma Research (MR308). This Phase I study compared single-dose pharmacokinetics (PK) of CTC with those of the individual reference products [immediate-release (IR) tramadol and celecoxib] alone and in open combination. Healthy adults aged 18-55 years were orally administered four treatments under fasted conditions (separated by 7-day wash-out period): 200 mg IR CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment 1); 100 mg IR tramadol (Treatment 2); 100 mg celecoxib (Treatment 3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment 4). Treatment sequence was assigned using computer-generated randomization. PK parameters were calculated using noncompartmental analysis with parameters for CTC adjusted according to reference product dose (100 mg). Thirty-six subjects (28 male, mean age 36 years) participated. Tramadol PK parameters for Treatments-1, -2 and -4, respectively, were 263, 346 and 349 ng ml -1 (mean maximum plasma concentration); 3039, 2979 and 3119 ng h ml -1 (mean cumulative area under the plasma concentration-time curve); and 2.7, 1.8 and 1.8 h (median time to maximum plasma concentration). For Treatments 1, 3 and 4, the respective celecoxib PK parameters were 313, 449 and 284 ng ml -1 ; 2183, 3093 and 2856 ng h ml -1 ; and 1.5, 2.3 and 3.0 h. No unexpected adverse events were reported. PK parameters of each API in CTC were modified by co-crystallization compared with marketed formulations of tramadol, celecoxib, and their open combination. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

An Exercise Prescription Intervention Program with Periodic Ergometric Grading

NASA Technical Reports Server (NTRS)

Owen, C. A.; Beard, E. F.

1970-01-01

A long term exercise prescription type of physical conditioning program has been available to executive personnel of the NASA Manned Spacecraft Center for the past two years. Periodic ergometric testing with a heart rate controlled, automatically programmed, bicycle ergometer is used to follow the individual's progress and appropriately alter his exercise prescription from time to time. Such a program appears feasible, and acceptance is excellent, dropout rates small and periodic testing participation good. Subjects training diligently can maintain satisfactory levels of conditioning.

Preventing a Washout.

ERIC Educational Resources Information Center

Poindexter, Dave

1996-01-01

Offers ideas for locating a roof leak. Discusses why many leaks originate in the roof's base flashings and the importance of knowing the roof's material makeup. Advocates keeping a roof-leak history and gives advice on performing inspections to check for leaks. Discusses how to find small holes in roofs. (RJM)

Effects of added antibiotics on the basic properties of anti-washout-type fast-setting calcium phosphate cement.

PubMed

Takechi, M; Miyamoto, Y; Ishikawa, K; Nagayama, M; Kon, M; Asaoka, K; Suzuki, K

1998-02-01

The effect of added antibiotics on the basic properties of anti-washout-type fast-setting calcium phosphate cement (aw-FSCPC) was investigated in a preliminary evaluation of aw-FSCPC containing drugs. Flomoxef sodium was employed as the antibiotic and was incorporated into the powder-phase aw-FSCPC at up to 10%. The setting time, consistency, wet diametral tensile strength (DTS) value, and porosity were measured for aw-FSCPC containing various amounts of flomoxef sodium. X-ray diffraction (XRD) analysis was also conducted for the identification of products. To evaluate the drug-release profile, set aw-FSCPC was immersed in saline and the released flomoxef sodium was determined at regular intervals. The spread area of the cement paste as an index of consistency of the cement increased progressively with the addition of flomoxef sodium, and it doubled when the aw-FSCPC contained 8% flomoxef sodium. In contrast, the wet DTS value decreased with increase in flomoxef sodium content. Bulk density measurement and scanning electron microscopic observation revealed that the set mass was more porous with the amount of flomoxef sodium contained in the aw-FSCPC. The XRD analysis revealed that formation of hydroxyapatite (HAP) from aw-FSCPC was reduced even after 24 h, when the aw-FSCPC contained flomoxef sodium at > or = 6%. Therefore, the decrease of wet DTS value was thought to be partly the result of the increased porosity and inhibition of HAP formation in aw-FSCPC containing large amounts of flomoxef sodium. The flomoxef sodium release from aw-FSCPC showed the typical profile observed in a skeleton-type drug delivery system (DDS). The rate of drug release from aw-FSCPC can be controlled by changing the concentration of sodium alginate. Although flomoxef sodium addition has certain disadvantageous effects on the basic properties of aw-FSCPC, we conclude that aw-FSCPC is a good candidate for potential use as a DDS carrier that may be useful in surgical operations.

Evolutionary dynamics of incubation periods.

PubMed

Ottino-Loffler, Bertrand; Scott, Jacob G; Strogatz, Steven H

2017-12-21

The incubation period for typhoid, polio, measles, leukemia and many other diseases follows a right-skewed, approximately lognormal distribution. Although this pattern was discovered more than sixty years ago, it remains an open question to explain its ubiquity. Here, we propose an explanation based on evolutionary dynamics on graphs. For simple models of a mutant or pathogen invading a network-structured population of healthy cells, we show that skewed distributions of incubation periods emerge for a wide range of assumptions about invader fitness, competition dynamics, and network structure. The skewness stems from stochastic mechanisms associated with two classic problems in probability theory: the coupon collector and the random walk. Unlike previous explanations that rely crucially on heterogeneity, our results hold even for homogeneous populations. Thus, we predict that two equally healthy individuals subjected to equal doses of equally pathogenic agents may, by chance alone, show remarkably different time courses of disease.

45 CFR 46.118 - Applications and proposals lacking definite plans for involvement of human subjects.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SERVICES GENERAL ADMINISTRATION PROTECTION OF HUMAN SUBJECTS Basic HHS Policy for Protection of Human... departments or agencies with the knowledge that subjects may be involved within the period of support, but...

Changing the Subject: English in London, 1945-1967

ERIC Educational Resources Information Center

Yandell, John

2014-01-01

Two recent books, "English Teachers in a Postwar Democracy: Emerging Choice in London Schools, 1945-1965" and "The London Association for the Teaching of English, 1947-67: A History," explore an important period in the development of English as a school subject and in the remaking of the professional identity of English…

Relative bioavailability of generic and branded acetylcysteine effervescent tablets: A single-dose, open-label, randomized-sequence, two-period crossover study in fasting healthy Chinese male volunteers.

PubMed

Liu, Yan-Mei; Liu, Yun; Lu, Chuan; Jia, Jing-Ying; Liu, Gang-Yi; Weng, Li-Ping; Wang, Jia-Yan; Li, Guo-Xiu; Wang, Wei; Li, Shui-Jun; Yu, Chen

2010-11-01

Acetylcysteine may be used as a muco- lytic agent for the treatment of chronic bronchitis, chronic obstructive pulmonary disease, and other pulmonary diseases complicated by the production of viscous mucus. However, little is known of its pharmacokinetic properties when given orally in healthy volunteers, particularly in a Chinese Han population. This study was conducted to provide support for the marketing of a generic product in China. The purpose of this study was to compare the pharmacokinetics and relative bioavailability of a generic test formulation and a branded reference formulation of acetylcysteine in fasting healthy Chinese male volunteers. A single-dose, open-label, randomized-sequence, 2-period crossover design with a 7-day washout period between doses was used in this study. Healthy Chinese male nonsmokers aged 18 to 40 years with a body mass index (BMI) of 19 to 25 kg/m(2) were selected. Eligible volunteers were randomly assigned to receive acetylcysteine 600 mg PO as either the test formulation (3 tablets of 200 mg each) or reference formulation (1 tablet of 600 mg) under fasting conditions. A total of 15 serial blood samples were collected over a 24-hour interval, and total plasma acetylcysteine concentrations were analyzed by a validated liquid chromatography-isotopic dilution mass spectrometry method. Pharmacokinetic parameters (C(max), T(max), t(½) AUC(0-t), and AUC(0-∞) were calculated and analyzed statistically. The 2 formulations were considered bioequivalent if the 90% CIs of the log-transformed ratios (test/reference) of C(max) and AUC were within the predetermined bioequivalence ranges (70%-143% for C(max); 80%-125% for AUC), as established by the State Food and Drug Administration of China. Tolerability was determined by vital signs, clinical laboratory tests, 12-lead ECGs, physical examinations, and interviews with the subjects about adverse events (AEs). A total of 24 healthy Chinese Han male volunteers were enrolled in and

Changes in prevalence of subjective fatigue during 14-day 6° head-down bed rest

NASA Astrophysics Data System (ADS)

Hirayanagi, Kaname; Natsuno, Toyoki; Shiozawa, Tomoki; Yamaguchi, Nobuhisa; Watanabe, Yoriko; Suzuki, Satomi; Iwase, Satoshi; Mano, Tadaaki; Yajima, Kazuyoshi

2009-06-01

The present study examines the prevalence of subjective fatigue in young healthy males during 14 days of 6° head-down bed rest (HDBR) by using a multidimensional questionnaire. Forty-one subjects completed the Subjective Fatigue Scale questionnaire to assess the fatigue-related complaints and symptoms. The questionnaire is composed of three sections, with 10 items each. The sections measured drowsiness and dullness (Section 1), difficulty in concentration (Section 2), and the projection of physical disintegration (Section 3). The subjects answered simple questions between 1400 and 1700 on 6 measurement days before and during the HDBR period. The prevalence rate of low back pain was markedly high (80.5%) on the second day and more than 50% in the first half of the HDBR period, and any complaints related to either a lack of sleep or a deterioration in the quality of sleep continued until the end of the HDBR period. Our findings may be useful in developing preventive strategies against physical and mental fatigue associated with prolonged HDBR, horizontal bed rest, and microgravity environments.

Subjective Ratings of Beauty and Aesthetics: Correlations With Statistical Image Properties in Western Oil Paintings

PubMed Central

Lehmann, Thomas; Redies, Christoph

2017-01-01

For centuries, oil paintings have been a major segment of the visual arts. The JenAesthetics data set consists of a large number of high-quality images of oil paintings of Western provenance from different art periods. With this database, we studied the relationship between objective image measures and subjective evaluations of the images, especially evaluations on aesthetics (defined as artistic value) and beauty (defined as individual liking). The objective measures represented low-level statistical image properties that have been associated with aesthetic value in previous research. Subjective rating scores on aesthetics and beauty correlated not only with each other but also with different combinations of the objective measures. Furthermore, we found that paintings from different art periods vary with regard to the objective measures, that is, they exhibit specific patterns of statistical image properties. In addition, clusters of participants preferred different combinations of these properties. In conclusion, the results of the present study provide evidence that statistical image properties vary between art periods and subject matters and, in addition, they correlate with the subjective evaluation of paintings by the participants. PMID:28694958

Two cholinesterase inhibitors trigger dissimilar effects on behavior and body weight in C57BL/6 mice: The case of chlorpyrifos and rivastigmine.

PubMed

Basaure, Pia; Peris-Sampedro, Fiona; Cabré, Maria; Reverte, Ingrid; Colomina, Maria Teresa

2017-02-01

Cholinesterases (ChE) are common targets of organophosphate (OP) pesticides and play a critical role in the pathology of some dementias. While chlorpyrifos (CPF) remains one of the most commonly used OPs in the world, numerous investigations have reported its neurotoxic potential and highlighted behavioral disturbances upon its administration. Rivastigmine currently serves to treat Alzheimer's disease, but it may induce cholinergic overstimulation in non-demented individuals. The present investigation aimed to compare the acute and delayed effects caused by both ChE inhibitors in adult C57BL/6 male mice. The animals were daily fed either a standard, a CPF- (5mg/kg body weight) or a rivastigmine-supplemented diet (1 or 2mg/kg body weight) for 8 weeks. After the treatment, we established an 8-week washout period to assess recovery. ChE enzyme activity, biomarkers, physical effects, and behavioral alterations were evaluated at different time points during the exposure and after the washout period. Both rivastigmine doses induced a time-dependent weight increase. CPF and rivastigmine inhibited brain acetylcholinesterase following an isoform-specific pattern. As for behavioral assessment, CPF negatively modulated learning strategies and impaired memory in a Barnes maze task at the end of the exposure. On the other hand, the low dose of rivastigmine improved memory recall at the end of the washout period in a Morris water maze. Indeed, our results endorse the positive effects of low doses of rivastigmine following a drug-free period in young mice. Therefore, doses and periodicity of treatment to improve cognition in elderly people upon rivastigmine administration should be revised. Copyright © 2016 Elsevier B.V. All rights reserved.

Individual survival curves comparing subjective and observed mortality risks.

PubMed

Bissonnette, Luc; Hurd, Michael D; Michaud, Pierre-Carl

2017-12-01

We compare individual survival curves constructed from objective (actual mortality) and elicited subjective information (probability of survival to a given target age). We develop a methodology to estimate jointly subjective and objective individual survival curves accounting for rounding on subjective reports of perceived survival. We make use of the long follow-up period in the Health and Retirement Study and the high quality of mortality data to estimate individual survival curves that feature both observed and unobserved heterogeneity. This allows us to compare objective and subjective estimates of remaining life expectancy for various groups and compare welfare effects of objective and subjective mortality risk using the life cycle model of consumption. We find that subjective and objective hazards are not the same. The median welfare loss from misperceptions of mortality risk when annuities are not available is 7% of current wealth at age 65 whereas more than 25% of respondents have losses larger than 60% of wealth. When annuities are available and exogenously given, the welfare loss is substantially lower. Copyright © 2017 John Wiley & Sons, Ltd.

Evolution of periodicity in periodical cicadas.

PubMed

Ito, Hiromu; Kakishima, Satoshi; Uehara, Takashi; Morita, Satoru; Koyama, Takuya; Sota, Teiji; Cooley, John R; Yoshimura, Jin

2015-09-14

Periodical cicadas (Magicicada spp.) in the USA are famous for their unique prime-numbered life cycles of 13 and 17 years and their nearly perfectly synchronized mass emergences. Because almost all known species of cicada are non-periodical, periodicity is assumed to be a derived state. A leading hypothesis for the evolution of periodicity in Magicicada implicates the decline in average temperature during glacial periods. During the evolution of periodicity, the determinant of maturation in ancestral cicadas is hypothesized to have switched from size dependence to time (period) dependence. The selection for the prime-numbered cycles should have taken place only after the fixation of periodicity. Here, we build an individual-based model of cicadas under conditions of climatic cooling to explore the fixation of periodicity. In our model, under cold environments, extremely long juvenile stages lead to extremely low adult densities, limiting mating opportunities and favouring the evolution of synchronized emergence. Our results indicate that these changes, which were triggered by glacial cooling, could have led to the fixation of periodicity in the non-periodical ancestors.

Evolution of periodicity in periodical cicadas

PubMed Central

Ito, Hiromu; Kakishima, Satoshi; Uehara, Takashi; Morita, Satoru; Koyama, Takuya; Sota, Teiji; Cooley, John R.; Yoshimura, Jin

2015-01-01

Periodical cicadas (Magicicada spp.) in the USA are famous for their unique prime-numbered life cycles of 13 and 17 years and their nearly perfectly synchronized mass emergences. Because almost all known species of cicada are non-periodical, periodicity is assumed to be a derived state. A leading hypothesis for the evolution of periodicity in Magicicada implicates the decline in average temperature during glacial periods. During the evolution of periodicity, the determinant of maturation in ancestral cicadas is hypothesized to have switched from size dependence to time (period) dependence. The selection for the prime-numbered cycles should have taken place only after the fixation of periodicity. Here, we build an individual-based model of cicadas under conditions of climatic cooling to explore the fixation of periodicity. In our model, under cold environments, extremely long juvenile stages lead to extremely low adult densities, limiting mating opportunities and favouring the evolution of synchronized emergence. Our results indicate that these changes, which were triggered by glacial cooling, could have led to the fixation of periodicity in the non-periodical ancestors. PMID:26365061

Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study.

PubMed

Choi, YoonJung; Lee, SeungHwan; Cho, Sang-Min; Kang, Won-Ho; Nam, Kyu-Yeol; Jang, In-Jin; Yu, Kyung-Sang

2016-01-01

A fixed-dose combination (FDC) of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects. A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography-tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs) of the geometric mean ratios of the two treatments for the maximum plasma concentration ( C max ) and the area under the concentration curve from time zero to the last quantifiable time point (AUC 0-t ) were estimated. Tolerability assessments were performed for all subjects who received the drug at least once. The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine besylate to amlodipine camsylate for the C max and AUC 0-t were 0.98 (0.94-1.01) and 0.97 (0.93-1.01), respectively. The corresponding values for losartan were 0.91 (0.81-1.02) and 1.05 (0.98-1.12), respectively. The incidence of adverse events was not significantly different between the two treatments, and both were well tolerated. An FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK parameters of amlodipine and losartan based on C max and AUC 0-t values. The amlodipine besylate/losartan potassium combination was well tolerated by healthy male

The role of FADS1/2 polymorphisms on cardiometabolic markers and fatty acid profiles in young adults consuming fish oil supplements.

PubMed

Roke, Kaitlin; Mutch, David M

2014-06-16

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 (n-3) fatty acids (FAs) known to influence cardiometabolic markers of health. Evidence suggests that single nucleotide polymorphisms (SNPs) in the fatty acid desaturase 1 and 2 (FADS1/2) gene cluster may influence an individual's response to n-3 FAs. This study examined the impact of a moderate daily dose of EPA and DHA fish oil supplements on cardiometabolic markers, FA levels in serum and red blood cells (RBC), and whether these endpoints were influenced by SNPs in FADS1/2. Young adults consumed fish oil supplements (1.8 g total EPA/DHA per day) for 12 weeks followed by an 8-week washout period. Serum and RBC FA profiles were analyzed every two weeks by gas chromatography. Two SNPs were genotyped: rs174537 in FADS1 and rs174576 in FADS2. Participants had significantly reduced levels of blood triglycerides (-13%) and glucose (-11%) by week 12; however, these benefits were lost during the washout period. EPA and DHA levels increased significantly in serum (+250% and +51%, respectively) and RBCs (+132% and +18%, respectively) within the first two weeks of supplementation and remained elevated throughout the 12-week period. EPA and DHA levels in RBCs only (not serum) remained significantly elevated (+37% and +24%, respectively) after the washout period. Minor allele carriers for both SNPs experienced greater increases in RBC EPA levels during supplementation; suggesting that genetic variation at this locus can influence an individual's response to fish oil supplements.

Effect of Terbinafine on Theophylline Pharmacokinetics in Healthy Volunteers

PubMed Central

Trépanier, Eric F.; Nafziger, Anne N.; Amsden, Guy W.

1998-01-01

Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) with and without multiple-dose terbinafine, and 11 blood samples were collected over 24 h. The study phases were separated by a 4-week washout period. Theophylline serum data were modeled via noncompartmental analysis. When the control phase (i.e., no terbinafine) was compared to the treatment phase (terbinafine), theophylline exposure (the area under the serum concentration-time curve from time zero to infinity) increased by 16% (P = 0.03), oral clearance decreased by 14% (P = 0.04), and half-life increased by 24% (P = 0.002). No significant changes in other theophylline pharmacokinetic parameters were evident. PMID:9517954

Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans.

PubMed

Allen, Jacob M; Mailing, Lucy J; Niemiro, Grace M; Moore, Rachel; Cook, Marc D; White, Bryan A; Holscher, Hannah D; Woods, Jeffrey A

2018-04-01

Exercise is associated with altered gut microbial composition, but studies have not investigated whether the gut microbiota and associated metabolites are modulated by exercise training in humans. We explored the impact of 6 wk of endurance exercise on the composition, functional capacity, and metabolic output of the gut microbiota in lean and obese adults with multiple-day dietary controls before outcome variable collection. Thirty-two lean (n = 18 [9 female]) and obese (n = 14 [11 female]), previously sedentary subjects participated in 6 wk of supervised, endurance-based exercise training (3 d·wk) that progressed from 30 to 60 min·d and from moderate (60% of HR reserve) to vigorous intensity (75% HR reserve). Subsequently, participants returned to a sedentary lifestyle activity for a 6-wk washout period. Fecal samples were collected before and after 6 wk of exercise, as well as after the sedentary washout period, with 3-d dietary controls in place before each collection. β-diversity analysis revealed that exercise-induced alterations of the gut microbiota were dependent on obesity status. Exercise increased fecal concentrations of short-chain fatty acids in lean, but not obese, participants. Exercise-induced shifts in metabolic output of the microbiota paralleled changes in bacterial genes and taxa capable of short-chain fatty acid production. Lastly, exercise-induced changes in the microbiota were largely reversed once exercise training ceased. These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent of diet and contingent on the sustainment of exercise.

Challenges to tracking subjects for follow-up research: a case study.

PubMed

Fenster, Judy

2009-01-01

This narrative presents issues faced by the author and her research assistants in attempting to locate 40 subjects who had participated in a child welfare research study two decades earlier. The experience of the researchers suggests that attempting to locate subjects, especially where contact has not been maintained over the years, may not be accomplished without considerable time and expense. The author reflects on possible contributors to the difficulties in contacting these participants, highlights some recent developments in techniques for locating subjects after long periods of time have elapsed, and discusses some relevant ethical dilemmas.

Comparison of Intermittent Fasting Versus Caloric Restriction in Obese Subjects: A Two Year Follow-Up.

PubMed

Aksungar, F B; Sarıkaya, M; Coskun, A; Serteser, M; Unsal, I

2017-01-01

Caloric restriction (CR) is proven to be effective in increasing life span and it is well known that, nutritional habits, sleeping pattern and meal frequency have profound effects on human health. In Ramadan some Muslims fast during the day-light hours for a month, providing us a unique model of intermittent fasting (IF) in humans. In the present study, we have investigated the effects of IF versus CR on the same non-diabetic obese subjects who were followed for two years according to the growth hormone (GH)/Insulin like growth factor (IGF)-1 axis and insulin resistance. Single-arm Interventional Human Study. 23 female subjects (Body Mass Index (BMI) 29-39, aged between 28-42years). Follow-up is designed as 12 months of CR, after which there was a month of IF and 11 months of CR again, to be totally 24 months. Subjects' daily diets were aligned as low calorie diet during CR and during the IF period, the same subjects fasted for 15 hours in a day for a month and there was no daily calorie restriction. Nutritional pattern was changed as 1 meal in the evening and a late supper before sleeping and no eating and drinking during the day light hours in the IF model. Subjects made brisk walking twice a day during the whole follow-up including both CR and IF periods. BMI, Blood glucose, insulin, TSH, GH, HbA1c, IGF-1, Homa-IR and urinary acetoacetate levels were monitored once in three months and twice in the fasting month. While subjects lost 1250 ± 372g monthly during the CR, in the IF period, weight loss was decreased to 473 ± 146 g. BMI of all subjects decreased gradually and as the BMI decreased, glucose, HbA1c, insulin, Homa-IR and TSH levels were decreased. GH levels were at baseline at the beginning, increased in the first six months and stayed steady during the CR and IF period than began decreasing after the IF period, while IGF-I increased gradually during the CR period and beginning with the 7th day of IF period, it decreased and kept on decreasing till the

Trajectories of Sleep Quality and Associations with Mood during the Perinatal Period.

PubMed

Tomfohr, Lianne M; Buliga, Elena; Letourneau, Nicole L; Campbell, Tavis S; Giesbrecht, Gerald F

2015-08-01

The aim of this study was to investigate trajectories of sleep quality and associations with mood in the perinatal period. Although it is commonly accepted that subjective sleep quality declines during pregnancy and the transition to parenthood, some women may follow qualitatively distinct trajectories. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Data were collected from 293 women at four time points: during early pregnancy, at Time 1 (T1; < 22 w gestational age [GA]; late pregnancy, at Time 2 (T2; 32 w GA); during the postnatal period at Time 3 (T3; 3 mo postpartum); and Time 4 (T4; 6 mo postpartum). A group-based semiparametric mixture model was used to estimate patterns of sleep quality throughout the perinatal period. Four trajectory groups were identified, including patterns defined by high sleep quality throughout (21.5%), mild decrease in sleep quality (59.5%), significant decrease in sleep quality (12.3%) and a group with poor sleep quality throughout (6.7%). Women who had the worst sleep quality at Time 1 and those who experienced significant increases in sleep problems throughout pregnancy were also the groups who reported the highest levels of anxiety and depressive symptoms in early pregnancy and the lowest levels of social support. After controlling for covariates, the groups with worst subjective sleep quality during pregnancy were also the most likely to experience high symptoms of depression in the postpartum period. Most of the women in our sample reported mild sleep disturbances through the perinatal period. A subgroup of women reported a significant decline in sleep quality from early to late pregnancy and another reported poor subjective sleep quality throughout pregnancy; these groups had the greatest risk of experiencing high symptoms of depression in the postpartum period. © 2015 Associated Professional Sleep Societies, LLC.

Muscle Synergies Facilitate Computational Prediction of Subject-Specific Walking Motions

PubMed Central

Meyer, Andrew J.; Eskinazi, Ilan; Jackson, Jennifer N.; Rao, Anil V.; Patten, Carolynn; Fregly, Benjamin J.

2016-01-01

Researchers have explored a variety of neurorehabilitation approaches to restore normal walking function following a stroke. However, there is currently no objective means for prescribing and implementing treatments that are likely to maximize recovery of walking function for any particular patient. As a first step toward optimizing neurorehabilitation effectiveness, this study develops and evaluates a patient-specific synergy-controlled neuromusculoskeletal simulation framework that can predict walking motions for an individual post-stroke. The main question we addressed was whether driving a subject-specific neuromusculoskeletal model with muscle synergy controls (5 per leg) facilitates generation of accurate walking predictions compared to a model driven by muscle activation controls (35 per leg) or joint torque controls (5 per leg). To explore this question, we developed a subject-specific neuromusculoskeletal model of a single high-functioning hemiparetic subject using instrumented treadmill walking data collected at the subject’s self-selected speed of 0.5 m/s. The model included subject-specific representations of lower-body kinematic structure, foot–ground contact behavior, electromyography-driven muscle force generation, and neural control limitations and remaining capabilities. Using direct collocation optimal control and the subject-specific model, we evaluated the ability of the three control approaches to predict the subject’s walking kinematics and kinetics at two speeds (0.5 and 0.8 m/s) for which experimental data were available from the subject. We also evaluated whether synergy controls could predict a physically realistic gait period at one speed (1.1 m/s) for which no experimental data were available. All three control approaches predicted the subject’s walking kinematics and kinetics (including ground reaction forces) well for the model calibration speed of 0.5 m/s. However, only activation and synergy controls could predict the

Effects of single doses of rabeprazole 20 mg and esomeprazole 40 mg on 24-h intragastric pH in healthy subjects.

PubMed

Warrington, Steve; Baisley, Kathy; Dunn, Kate; Boyce, Malcolm; Morocutti, Anna

2006-09-01

To compare antisecretory effects of single doses of rabeprazole and esomeprazole. Open, randomised, 2-way crossover, clinical pharmacology study. 24 healthy subjects (10 men; mean age 26.2 y) received a single dose of rabeprazole 20 mg or esomeprazole 40 mg, with a 14-day 'washout'. Intragastric pH was recorded continuously from 24 h before to 24 h after dosing. Mean intragastric pH was higher after esomeprazole than rabeprazole during 0-5 h after dosing (P=0.0001); the reverse was true from 14-24 h (P=0.0002). Mean % time pH>3 and >4 was greater after esomeprazole than rabeprazole during 0-14 h (P=0.041 and 0.044), but the reverse was true during 14-24 h (P=0.0005 and 0.001). In the 0-24 h interval as a whole, there was no difference between treatments in mean pH or % time pH>3 or >4. Single-dose rabeprazole 20 mg was as effective as esomeprazole 40 mg in increasing intragastric pH and maintaining pH>3 and >4, despite the 2-fold difference in dose.

The clinical utility of lung clearance index in early cystic fibrosis lung disease is not impacted by the number of multiple-breath washout trials

PubMed Central

Foong, Rachel E.; Harper, Alana J.; King, Louise; Turkovic, Lidija; Davis, Miriam; Clem, Charles C.; Davis, Stephanie D.; Ranganathan, Sarath; Hall, Graham L.

2018-01-01

The lung clearance index (LCI) from the multiple-breath washout (MBW) test is a promising surveillance tool for pre-school children with cystic fibrosis (CF). Current guidelines for MBW testing recommend that three acceptable trials are required. However, success rates to achieve these criteria are low in children aged <7 years and feasibility may improve with modified pre-school criteria that accepts tests with two acceptable trials. This study aimed to determine if relationships between LCI and clinical outcomes of CF lung disease differ when only two acceptable MBW trials are assessed. Healthy children and children with CF aged 3–6 years were recruited for MBW testing. Children with CF also underwent bronchoalveolar lavage fluid collection and a chest computed tomography scan. MBW feasibility increased from 46% to 75% when tests with two trials were deemed acceptable compared with tests where three acceptable trials were required. Relationships between MBW outcomes and markers of pulmonary inflammation, infection and structural lung disease were not different between tests with three acceptable trials compared with tests with two acceptable trials. This study indicates that pre-school MBW data from two acceptable trials may provide sufficient information on ventilation distribution if three acceptable trials are not possible. PMID:29707562

Evolutionary dynamics of incubation periods

PubMed Central

Ottino-Loffler, Bertrand; Scott, Jacob G

2017-01-01

The incubation period for typhoid, polio, measles, leukemia and many other diseases follows a right-skewed, approximately lognormal distribution. Although this pattern was discovered more than sixty years ago, it remains an open question to explain its ubiquity. Here, we propose an explanation based on evolutionary dynamics on graphs. For simple models of a mutant or pathogen invading a network-structured population of healthy cells, we show that skewed distributions of incubation periods emerge for a wide range of assumptions about invader fitness, competition dynamics, and network structure. The skewness stems from stochastic mechanisms associated with two classic problems in probability theory: the coupon collector and the random walk. Unlike previous explanations that rely crucially on heterogeneity, our results hold even for homogeneous populations. Thus, we predict that two equally healthy individuals subjected to equal doses of equally pathogenic agents may, by chance alone, show remarkably different time courses of disease. PMID:29266000

Improvement of antioxidant status after Brazil nut intake in hypertensive and dyslipidemic subjects.

PubMed

Huguenin, Grazielle V B; Oliveira, Glaucia M M; Moreira, Annie S B; Saint'Pierre, Tatiana D; Gonçalves, Rodrigo A; Pinheiro-Mulder, Alessandra R; Teodoro, Anderson J; Luiz, Ronir R; Rosa, Glorimar

2015-05-29

To investigate the effect of partially defatted Granulated Brazil nut (GBN) on biomarkers of oxidative stress and antioxidant status of hypertensive and dyslipidemic patients on nutrition and drug approaches. Ninety one hypertensive and dyslipidemic subjects of both genders (51.6 % men), mean age 62.1 ± 9.3 years, performed a randomized crossover trial, double-blind, placebo controlled. Subjects received a diet and partially defatted GBN 13 g per day (≈227.5 μg/day of selenium) or placebo for twelve weeks with four-week washout interval. Anthropometric, laboratory and clinic characteristics were investigated at baseline. Plasma selenium (Se), plasma glutathione peroxidase (GPx3) activity, total antioxidant capacity (TAC), 8-epi PGF2α and oxidized LDL were evaluated at the beginning and in the end of each intervention. GBN intake significantly increased plasma Se from 87.0 ± 16.8 to 180.6 ± 67.1 μg/L, increased GPx3 activity in 24,8% (from 112.66 ± 40.09 to 128.32 ± 38.31 nmol/min/mL, p < 0,05), and reduced 3.25% of oxidized-LDL levels (from 66.31 ± 23.59 to 60.68 ± 20.88 U/L, p < 0.05). An inverse association between GPx3 and oxidized LDL levels was observed after supplementation with GBN by simple model (β -0.232, p = 0.032) and after adjustment for gender, age, diabetes and BMI (β -0.298, p = 0.008). There wasn't association between GPx3 and 8-epi PGF2α (β -0.209, p = 0.052) by simple model. The partially defatted GBN intake has a potential benefit to increase plasma selenium, increase enzymatic antioxidant activity of GPx3 and to reduction oxidation in LDL in hypertensive and dyslipidemic patients. ClinicalTrials.gov Identifier NCT01990391; November 20, 2013.

Trajectories of Sleep Quality and Associations with Mood during the Perinatal Period

PubMed Central

Tomfohr, Lianne M.; Buliga, Elena; Letourneau, Nicole L.; Campbell, Tavis S.; Giesbrecht, Gerald F.

2015-01-01

Objective: The aim of this study was to investigate trajectories of sleep quality and associations with mood in the perinatal period. Although it is commonly accepted that subjective sleep quality declines during pregnancy and the transition to parenthood, some women may follow qualitatively distinct trajectories. Design, Setting, and Participants: Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Data were collected from 293 women at four time points: during early pregnancy, at Time 1 (T1; < 22 w gestational age [GA]; late pregnancy, at Time 2 (T2; 32 w GA); during the postnatal period at Time 3 (T3; 3 mo postpartum); and Time 4 (T4; 6 mo postpartum). A group-based semiparametric mixture model was used to estimate patterns of sleep quality throughout the perinatal period. Results: Four trajectory groups were identified, including patterns defined by high sleep quality throughout (21.5%), mild decrease in sleep quality (59.5%), significant decrease in sleep quality (12.3%) and a group with poor sleep quality throughout (6.7%). Women who had the worst sleep quality at Time 1 and those who experienced significant increases in sleep problems throughout pregnancy were also the groups who reported the highest levels of anxiety and depressive symptoms in early pregnancy and the lowest levels of social support. After controlling for covariates, the groups with worst subjective sleep quality during pregnancy were also the most likely to experience high symptoms of depression in the postpartum period. Conclusions: Most of the women in our sample reported mild sleep disturbances through the perinatal period. A subgroup of women reported a significant decline in sleep quality from early to late pregnancy and another reported poor subjective sleep quality throughout pregnancy; these groups had the greatest risk of experiencing high symptoms of depression in the postpartum period. Citation: Tomfohr LM, Buliga E, Letourneau NL, Campbell TS, Giesbrecht GF

Long-term results of treatment with diquafosol ophthalmic solution for aqueous-deficient dry eye.

PubMed

Koh, Shizuka; Ikeda, Chikako; Takai, Yoshihiro; Watanabe, Hitoshi; Maeda, Naoyuki; Nishida, Kohji

2013-09-01

To evaluate the preliminary long-term efficacy of diquafosol ophthalmic solution for aqueous-deficient dry eye. Fifteen patients with mild-to-moderate aqueous-deficient dry eye were enrolled. After a washout period, the patients were treated with 3 % diquafosol ophthalmic solution for 6 months. We assessed 12 subjective dry eye symptoms, corneal and conjunctival staining with fluorescein, tear film break-up time (BUT), lower tear meniscus height measured with anterior-segment optical coherence tomography, Schirmer's testing, and adverse reactions at baseline and 1, 3, and 6 months after the start of treatment. Treatment with diquafosol ophthalmic solution significantly improved dry eye symptoms, corneal staining, BUT, and tear meniscus height at 1 month and maintained the effectiveness for 6 months. Conjunctival staining significantly improved 3 and 6 months after treatment. No significant adverse reactions developed. Prolonged use of diquafosol ophthalmic solution for 6 months produced significant improvement both subjectively (dry eye symptom score) and objectively (ocular staining score and tear function tests) for aqueous-deficient dry eye.

NREM sleep architecture and relation to GH/IGF-1 axis in Laron syndrome.

PubMed

Verrillo, Elisabetta; Bizzarri, Carla; Cappa, Marco; Bruni, Oliviero; Pavone, Martino; Cutrera, Renato

2010-01-01

Laron syndrome (LS), known as growth hormone (GH) receptor deficiency, is a rare form of inherited GH resistance. Sleep disorders were described as a common feature of adult LS patients, while no data are available in children. Bi-directional interactions between human sleep and the somatotropic system were previously described, mainly between slow wave sleep and the nocturnal GH surge. To analyze the sleep macro- and microstructure in LS and to evaluate the influence of substitutive insulin-like growth factor 1 (IGF-1) therapy on it. Two young LS females underwent polysomnography; the first study was performed during IGF-1 therapy, the second one after a 3-month wash-out period. In both patients, the sleep macrostructure showed that time in bed, sleep period time, total sleep time, sleep efficiency and rapid eye movement (REM) percentage were all increased during wash-out. The sleep microstructure (cyclic alternating pattern: CAP) showed significantly higher EEG slow oscillations (A1%) in NREM sleep, both during IGF-1 therapy and wash-out. Sleep macrostructure in LS children is slightly affected by substitutive IGF-1 therapy. Sleep microstructure shows an increase of A1%, probably related to abnormally high hypothalamic GHRH secretion, due to GH insensitivity. Copyright 2010 S. Karger AG, Basel.

Consuming Two Eggs per Day, as Compared to an Oatmeal Breakfast, Decreases Plasma Ghrelin while Maintaining the LDL/HDL Ratio.

PubMed

Missimer, Amanda; DiMarco, Diana M; Andersen, Catherine J; Murillo, Ana Gabriela; Vergara-Jimenez, Marcela; Fernandez, Maria Luz

2017-01-29

Eggs contain high quality protein, vitamins, minerals and antioxidants, yet regular consumption is still met with uncertainty. Therefore, the purpose of this study was to compare the effects of consuming two eggs per day or a heart-healthy oatmeal breakfast on biomarkers of cardiovascular disease (CVD) risk and satiety measures in a young, healthy population. Fifty subjects participated in a randomized crossover clinical intervention; subjects were randomly allocated to consume either two eggs or one packet of oatmeal per day for breakfast for four weeks. After a three-week washout period, participants were allocated to the alternative breakfast. Fasting blood samples were collected at the end of each intervention period to assess plasma lipids and plasma ghrelin. Subjects completed visual analog scales (VAS) concurrent to dietary records to assess satiety and hunger. Along with an increase in cholesterol intake, there were significant increases in both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol following the egg consumption period ( p < 0.01). However, there was no difference in the LDL/HDL ratio, a recognized biomarker of CVD risk, nor in the plasma glucose, triglycerides or liver enzymes, between diet periods. Several self-reported satiety measures were increased following the consumption of eggs, which were associated with lower plasma ghrelin concentrations ( p < 0.05). These results demonstrate that compared to an oatmeal breakfast, two eggs per day do not adversely affect the biomarkers associated with CVD risk, but increase satiety throughout the day in a young healthy population.

Functional brain segmentation using inter-subject correlation in fMRI.

PubMed

Kauppi, Jukka-Pekka; Pajula, Juha; Niemi, Jari; Hari, Riitta; Tohka, Jussi

2017-05-01

The human brain continuously processes massive amounts of rich sensory information. To better understand such highly complex brain processes, modern neuroimaging studies are increasingly utilizing experimental setups that better mimic daily-life situations. A new exploratory data-analysis approach, functional segmentation inter-subject correlation analysis (FuSeISC), was proposed to facilitate the analysis of functional magnetic resonance (fMRI) data sets collected in these experiments. The method provides a new type of functional segmentation of brain areas, not only characterizing areas that display similar processing across subjects but also areas in which processing across subjects is highly variable. FuSeISC was tested using fMRI data sets collected during traditional block-design stimuli (37 subjects) as well as naturalistic auditory narratives (19 subjects). The method identified spatially local and/or bilaterally symmetric clusters in several cortical areas, many of which are known to be processing the types of stimuli used in the experiments. The method is not only useful for spatial exploration of large fMRI data sets obtained using naturalistic stimuli, but also has other potential applications, such as generation of a functional brain atlases including both lower- and higher-order processing areas. Finally, as a part of FuSeISC, a criterion-based sparsification of the shared nearest-neighbor graph was proposed for detecting clusters in noisy data. In the tests with synthetic data, this technique was superior to well-known clustering methods, such as Ward's method, affinity propagation, and K-means ++. Hum Brain Mapp 38:2643-2665, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Autoantibodies against AT1 and α1-adrenergic receptors predict arterial stiffness progression in normotensive subjects over a 5-year period.

PubMed

Li, Gang; Cao, Zhe; Wu, Xiao-Wei; Wu, Hui-Kun; Ma, Yi; Wu, Bin; Wang, Wei-Qing; Cheng, Jian; Zhou, Zi-Hua; Tu, Yuan-Chao

2017-12-15

Arterial stiffness is an independent indicator of cardiovascular risk. Autoantibodies (AAs) against angiotensin AT 1 receptor (AT 1 -AAs) and α 1 -adrenergic receptor (α 1 -AAs) are important in the pathogenesis of hypertension. We identified the types of AT 1 -AAs and α 1 -AAs in normotensive subjects, with the aim of determining whether these antibodies predict aortic stiffness progression. Carotid-femoral pulse wave velocity (cf-PWV) was used to measure aortic stiffness. Overall, 816 subjects (71% of those invited) underwent a medical examination and evaluation of aortic stiffness. The types of AT 1 -AAs and α 1 -AAs were measured at baseline. Meanwhile, plasma renin, angiotensin II (Ang II), and norepinephrine (NE) concentrations were measured at baseline and follow-up. Baseline mean cf-PWV was 9.90 ± 0.84 m/s and follow-up was 10.51 ± 1.12 m/s. The annualized ΔPWV was 0.12 ± 0.08 m/s/year. At the end of follow-up, 129 normotensive subjects developed hypertension and 144 subjects had PWV progression. After adjustment for covariates, AA type was independently associated with ΔPWV, annualized ΔPWV, and abnormal PWV. In our study, the risk of developing hypertension (RR =2.028, 95% CI: 1.227-3.351, P =0.006) and PWV progression (RR =2.910, 95% CI: 1.612-5.253, P <0.001) in AA-positive subjects was significantly higher than that in AA-negative subjects. Receiver operating characteristic (ROC) curve showed AA had an identify power to discriminate subjects with or without PWV and hypertension progression. We have shown for the first time that the types of A 1 -AAs and α 1 -AAs are independent predictors for aortic stiffness progression in normotensive subjects. Our data collectively support the utility of these AAs as potential markers of aortic stiffness. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

NASA thesaurus alphabetical update: Subject terms for indexing scientific and technical information

NASA Technical Reports Server (NTRS)

1971-01-01

The NASA THESAURUS - ALPHABETICAL UPDATE is an alphabetical listing of all subject terms (postable and nonpostable) that are currently approved for use in the NASA scientific and technical information system. Contained in the listing are the subject terms that were listed in the Preliminary Edition of the NASA THESAURUS and the additional subject terms that were approved during the period January 1, 1967 June 30, 1971. Complete Thesaurus structuring, including scope notes, category assignments, and cross-references, is provided for each term as appropriate.

Molecular evidence that oral supplementation with lycopene or lutein protects human skin against ultraviolet radiation: results from a double-blinded, placebo-controlled, crossover study.

PubMed

Grether-Beck, S; Marini, A; Jaenicke, T; Stahl, W; Krutmann, J

2017-05-01

Increasing evidence suggests photoprotection by oral supplementation with β-carotene and lycopene. To examine the capacity of lycopene-rich tomato nutrient complex (TNC) and lutein, to protect against ultraviolet (UV)A/B and UVA1 radiation at a molecular level. In a placebo-controlled, double-blinded, randomized, crossover study two active treatments containing either TNC or lutein were assessed for their capacity to decrease the expression of UVA1 the radiation-inducible genes HO1, ICAM1 and MMP1. Sixty-five healthy volunteers were allocated to four treatment groups and subjected to a 2-week washout phase, followed by two 12-week treatment phases separated by another 2 weeks of washout. Volunteers started either with active treatment and were then switched to placebo, or vice versa. At the beginning and at the end of each treatment phase skin was irradiated and 24 h later biopsies were taken from untreated, UVA/B- and UVA1-irradiated skin for subsequent reverse transcriptase polymerase chain reaction analysis of gene expression. Moreover, blood samples were taken after the washout and the treatment phases for assessment of carotenoids. TNC completely inhibited UVA1- and UVA/B-induced upregulation of heme-oxygenase 1, intercellular adhesion molecule 1 and matrix metallopeptidase 1 mRNA, no matter the sequence (anova, P < 0·05). In contrast, lutein provided complete protection if it was taken in the first period but showed significantly smaller effects in the second sequence compared with TNC. Assuming the role of these genes as indicators of oxidative stress, photodermatoses and photoageing, these results might indicate that TNC and lutein could protect against solar radiation-induced health damage. © 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

The Psychosocial Influences of Waiting Periods on Patients Undergoing Endoscopic Submucosal Dissection.

PubMed

Nagao, Noriko; Tsuchiya, Aya; Ando, Sae; Arita, Mizue; Toyonaga, Takashi; Miyawaki, Ikuko

This study aimed to clarify psychosocial influences of waiting periods on patients undergoing endoscopic submucosal dissection for cancer at an advanced medical care facility in Japan. Subjects were consenting patients hospitalized from 2009 to 2010. Qualitative and quantitative data were gathered about patients' characteristics, disease and stage, and waiting period. Qualitative content analysis was used to analyze free statements and interview data. Subjects included 154 patients with an average wait period of 46.28 days for admission. Qualitative analysis revealed the following wait period perceptions. For calmness, results indicated (1) no anxiety, (2) relief based on doctors' positive judgment, (3) whatever happens/no choice, and (4) trust in doctor. For uneasiness, perceptions included (1) the sooner, the better/eagerly waiting, (2) anxiety and concern, and (3) emotional instability. Four waiting period coping types were identified: (1) making phone inquiries, (2) busy and forgot about the medical procedure, (3) relief from anxiety, and (4) unable to function well in daily life. Patients need to be educated about cancer progression and provided an estimated wait time. They also require more information about how to manage daily life such as monitoring factors from the nursing domain including physical condition, digestive symptoms, diet, and exercise.

The Psychosocial Influences of Waiting Periods on Patients Undergoing Endoscopic Submucosal Dissection

PubMed Central

Tsuchiya, Aya; Ando, Sae; Arita, Mizue; Toyonaga, Takashi; Miyawaki, Ikuko

2017-01-01

This study aimed to clarify psychosocial influences of waiting periods on patients undergoing endoscopic submucosal dissection for cancer at an advanced medical care facility in Japan. Subjects were consenting patients hospitalized from 2009 to 2010. Qualitative and quantitative data were gathered about patients' characteristics, disease and stage, and waiting period. Qualitative content analysis was used to analyze free statements and interview data. Subjects included 154 patients with an average wait period of 46.28 days for admission. Qualitative analysis revealed the following wait period perceptions. For calmness, results indicated (1) no anxiety, (2) relief based on doctors' positive judgment, (3) whatever happens/no choice, and (4) trust in doctor. For uneasiness, perceptions included (1) the sooner, the better/eagerly waiting, (2) anxiety and concern, and (3) emotional instability. Four waiting period coping types were identified: (1) making phone inquiries, (2) busy and forgot about the medical procedure, (3) relief from anxiety, and (4) unable to function well in daily life. Patients need to be educated about cancer progression and provided an estimated wait time. They also require more information about how to manage daily life such as monitoring factors from the nursing domain including physical condition, digestive symptoms, diet, and exercise. PMID:26987103

Urinary stone risk and cola consumption.

PubMed

Herrel, Lindsey; Pattaras, John; Solomon, Tania; Ogan, Kenneth

2012-11-01

To evaluate the effect of cola consumption on urinary stone risk factors in a controlled metabolic environment with a prospective cross-over study. Thirteen participants (10 normal and 3 calcium oxalate stone-formers) underwent 2 6-day phases on a controlled metabolic diet. During phase 1, subjects ingested 1 liter of cola daily, followed by a 3-week washout period. During phase 2, subjects ingested 1 liter of deionized water daily. Twenty-four-hour urine collections and serum metabolic panels were obtained for stone risk factors at the end of each phase. Urine and serum results of the cola phase were compared with those of the water phase. Normal subjects and stone-formers were combined for analysis after determining no significant difference between the 2 groups. No significant differences were found among cola and water treatment groups for normal subjects, stone-formers, or the pooled group. Cola exerts no detectable change in urinary risk factors associated with calcium oxalate stone formation. Cola consumption may not increase stone risk and may be an acceptable alternative source of daily fluid for patients unwilling to increase water consumption. Copyright © 2012 Elsevier Inc. All rights reserved.

Simulations of light effects on the human circadian pacemaker: implications for assessment of intrinsic period

NASA Technical Reports Server (NTRS)

Klerman, E. B.; Dijk, D. J.; Kronauer, R. E.; Czeisler, C. A.

1996-01-01

The sensitivity of the human circadian system to light has been the subject of considerable debate. Using computer simulations of a recent quantitative model for the effects of light on the human circadian system, we investigated these effects of light during different experimental protocols. The results of the simulations indicate that the nonuniform distribution over the circadian cycle of exposure to ordinary room light seen in classical free-run studies, in which subjects select their exposure to light and darkness, can result in an observed period of approximately 25 h, even when the intrinsic period of the subject's endogenous circadian pacemaker is much closer to 24 h. Other simulation results suggest that accurate assessment of the true intrinsic period of the human circadian pacemaker requires low ambient light intensities (approximately 10-15 lx) during scheduled wake episodes, desynchrony of the imposed light-dark cycle from the endogenous circadian oscillator, and a study length of at least 20 days. Although these simulations await further experimental substantiation, they highlight the sensitivity to light of the human circadian system and the potential confounding influence of light on the assessment of the intrinsic period of the circadian pacemaker.

Special interests and subjective wellbeing in autistic adults.

PubMed

Grove, Rachel; Hoekstra, Rosa A; Wierda, Marlies; Begeer, Sander

2018-05-01

Special interests form part of the core features of autism. However, to date there has been limited research focusing on the role of special interests in the lives of autistic adults. This study surveyed autistic adults on their special interest topics, intensity, and motivation. It also assessed the relationship between special interests and a range of quality of life measures including subjective wellbeing and domain specific life satisfaction. About two thirds of the sample reported having a special interest, with relatively more males reporting a special interest than females. Special interest topics included computers, autism, music, nature and gardening. Most autistic adults engaged in more than one special interest, highlighting that these interests may not be as narrow as previously described. There were no differences in subjective wellbeing between autistic adults with and without special interests. However, for autistic adults who did have special interests, motivation for engaging in special interests was associated with increased subjective wellbeing. This indicates that motivation may play an important role in our understanding of special interests in autism. Special interests had a positive impact on autistic adults and were associated with higher subjective wellbeing and satisfaction across specific life domains including social contact and leisure. However, a very high intensity of engagement with special interests was negatively related to wellbeing. Combined, these findings have important implications for the role of special interests in the lives of autistic adults. Autism Res 2018, 11: 766-775. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Autistic adults reported having special interests in a range of topics, including computers, music, autism, nature and gardening. Special interests were associated with a number of positive outcomes for autistic adults. They were also related to subjective wellbeing and

Bioequivalence of HTX-019 (aprepitant IV) and fosaprepitant in healthy subjects: a Phase I, open-label, randomized, two-way crossover evaluation.

PubMed

Ottoboni, Tom; Keller, Mary Rose; Cravets, Matt; Clendeninn, Neil; Quart, Barry

2018-01-01

Fosaprepitant, an intravenous (IV) aprepitant prodrug for chemotherapy-induced nausea and vomiting prophylaxis, is associated with systemic and infusion-site reactions attributed in part to its surfactant, polysorbate 80. HTX-019 is an IV aprepitant formulation free of polysorbate 80 and other synthetic surfactants. This open-label, single-dose, randomized, two-way crossover bioequivalence study compared pharmacokinetics and safety of HTX-019 and fosaprepitant. Healthy subjects received single-dose HTX-019 (130 mg) or fosaprepitant (150 mg) IV over 30 min, with ≥7-day washout between doses. Blood samples were evaluated for pharmacokinetics and bioequivalence; safety evaluation included treatment-emergent adverse events (TEAEs) and serious adverse events. Ninety-seven of one hundred enrolled subjects completed the study. Baseline characteristics were comparable between treatment sequences. For HTX-019, mean (percent coefficient of variation) area under the curve (AUC) from time 0 to time of last measurable plasma concentration (AUC 0-t ), AUC from time 0 to infinity (AUC 0-inf ), and plasma concentration at 12 h (C 12 h ) for HTX-019 were 43,729 h*ng/mL (32.7), 45,460 h*ng/mL (36.8), and 988.4 ng/mL (27.5), respectively; corresponding fosaprepitant values were 44,130 h*ng/mL (32.0), 46,163 h*ng/mL (36.6), and 1,022 ng/mL (28.5). Also, 90% CIs (94.186-101.354) were within bioequivalence bounds (80%-125%). Within 1 h following infusion start, one (1%) HTX-019 recipient reported one TEAE, while 20 (20%) fosaprepitant recipients reported 32 TEAEs. Dyspnea occurred in three fosaprepitant recipients (at <1 min in two subjects and at 18 min in one subject, considered study drug related) and one HTX-019 recipient (at 120 h, associated with a respiratory tract infection and considered not related to the study drug). No severe TEAEs, serious adverse events, or deaths occurred; all TEAEs resolved. HTX-019 was bioequivalent to fosaprepitant and may provide a safer alternative

Earthworm Activity and the Potential for Enhanced Leaching of Inorganic Elements in Soils

NASA Astrophysics Data System (ADS)

Gruau, G.; Ablain, F.; Cluzeau, D.

2002-12-01

The potential influence of earthworms on the mobility of soil inorganic constituents was experimentally investigated. Six 20 cm long and 15 cm i.d. columns were packed with soil (loamy material, Paris basin, France). Three earthworm specimens - Lombricus terrestris - were introduced into 3 of the 6 columns (earthworm treatment or ET), the remaing 3 being used to study changes in water composition and solute fluxes without earthworms (control treatment or CT). The 6 columns were operated for 8 weeks and were subjected to 100 ml addition of distilled water at 1, 8, 15, 22, 29, 36, 43 and 50 days. Effluents were collected weekly, filtered and analysed for their Dissolved Organic Carbon (DOC) as well as Si, Na, K, Mg, Ca, Fe, Mn, Al, Sr, Ba, Cu, Zn, Cr, Cd, REE and U concentrations. Replicates yielded extremely consistent results, with standard deviations generally lower than 10%. Effluent volumes were greatest during ET simulations (28% difference on a cumulative basis), which can be attributed to the construction by Lombricus terrestris of permanent vertical burrows into the soil columns. Different temporal chemical trends were observed depending on whether earthworms were present or not. During ET simulations, a washout phenomenon occurred for DOC, Ca, Mg, Fe, Ba, Sr, Cu and U during the startup outflow period (week 2). This washout was followed by a period of apparent equilibrium with concentrations in ET effluents remaining roughly constant for all solutes except REE, Zn and to a lesser extent Mn. No such washout nor equilibrium period was observed during CT simulations. Instead, concentrations in Ca, Mg, Fe, Ba, Sr, Cr and Cu decreased from week 2 to week 8, while those in other solutes increased from week 2 to week 5, then declining untill week 8. For many elements (not all), final (equilibrium?) concentrations (8 weeks simulation) were highest in ET effluents (e.g. 17% higher for Ca and Na; 30% higher for Zn), despite the enhanced infiltration rate (and thus

The efficacy of periodic +Gz exposure in the prevention of bedrest induced orthostatic intolerance

NASA Technical Reports Server (NTRS)

Ludwig, D. A.; Vernikos, J.; Duvoisin, M. R; Stinn, J. L.

1992-01-01

What is the most efficient dosage of periodic exposure to positive 1G(z) during microgravity to maintain a functional upright position after returning to a positive 1G(z) environment? The answer has implications for the type of countermeasures astronauts will be required to perform during long term space flight. Methods: Nine males were subjected to four different positive 1G exposure protocols plus a control protocol ('zero G(z)') during four days of continuous bedrest. The four positive 1G(z) exposures consisted of periodic standing or walking, each for a total period of two or four hours. Each subject was returned for bedrest on five different occasions over a period of approximately one year to obtain data on each of the nine subjects across all four positive 1G(z) treatments and the control. A 30 min tilt test was used to measure orthostatic response during pre and post bedrest. Results: In terms of survival rate (percentage of subjects who did not faint after 30 sec of tilt), four hours of intermittent standing was the only protocol that maintained a rate comparable to pre bedrest levels (87.5 percent). Although the other three positive 1G(z) protocols performed better than the 'zero G(z) control (22.2 percent), only the four hour standing returned post bedrest survival rates to pre bedrest levels. Conclusions: The results will need to be evaluated with regards to a variety of other physiological systems which are known to decondition during microgravitry.

Calcium phosphate supplementation increases faecal Lactobacillus spp. in a randomised trial of young adults.

PubMed

Dahl, W J; Ford, A L; Coppola, J A; Lopez, D; Combs, W; Rohani, A; Ukhanova, M; Culpepper, T; Tompkins, T A; Christman, M; Mai, V

2016-02-01

The aim of the studies was to determine the effects of calcium carbonate and calcium phosphate supplementation on faecal Lactobacillus spp., with and without a probiotic supplement, in healthy adults. Study 1 comprised of a randomised, double-blind, crossover design; participants (n=15) received 2 capsules/d of 250 mg elemental calcium as calcium carbonate (Ca1) and calcium phosphate (Ca2) each for 2-week periods, with 2-week baseline and washout periods. Study 2 was a randomised, double-blind, crossover design; participants (n=17) received 2 capsules/d of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 (probiotic) alone, the probiotic with 2 capsules/d of Ca1, and probiotic with 2 capsules/d of Ca2 each for 2-week periods with 2-week baseline and washout periods. In both studies, stools were collected during the baseline, intervention and washout periods for Lactobacillus spp. quantification and qPCR analyses. Participants completed daily questionnaires of stool frequency and compliance. In Study 1, neither calcium supplement influenced viable counts of resident Lactobacillus spp., genome equivalents of lactic acid bacteria or stool frequency. In Study 2, faecal Lactobacillus spp. counts were significantly enhanced from baseline when the probiotic was administered with Ca2 (4.83±0.30, 5.79±0.31) (P=0.02), but not with Ca1 (4.98±0.31) or with the probiotic alone (5.36±0.31, 5.55±0.29) (not significant). Detection of L. helveticus R0052 and L. rhamnosus R0011 was significantly increased with all treatments, but did not differ among treatments. There were no changes in weekly stool frequency. Calcium phosphate co-administration may increase gastrointestinal survival of orally-administered Lactobacillus spp.

A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study.

PubMed

Ridha, Basil H; Crutch, Sebastian; Cutler, Dawn; Frost, Christopher; Knight, William; Barker, Suzie; Epie, Norah; Warrington, Elizabeth K; Kukkastenvehmas, Riitta; Douglas, Jane; Rossor, Martin N

2018-05-01

The study investigated whether donepezil exerts symptomatic benefit in patients with posterior cortical atrophy (PCA), an atypical variant of Alzheimer's disease. A single-centre, double-blind, placebo-controlled, cross-over clinical trial was performed to assess the efficacy of donepezil in patients with PCA. Each patient received either donepezil (5 mg once daily in the first 6 weeks and 10 mg once daily in the second 6 weeks) or placebo for 12 weeks. After a 2-week washout period, each patient received the other treatment arm during the following 12 weeks followed by another 2-week washout period. The primary outcome was the Mini-Mental State Examination (MMSE) at 12 weeks. Secondary outcome measures were five neuropsychological tests reflecting parieto-occipital function. Intention-to-treat analysis was used. For each outcome measure, carry-over effects were first assessed. If present, then analysis was restricted to the first 12-week period. Otherwise, the standard approach to the analysis of a 2 × 2 cross-over trial was used. Eighteen patients (13 females) were recruited (mean age 61.6 years). There was a protocol violation in one patient, who subsequently withdrew from the study due to gastrointestinal side effects. There was statistically significant (p < 0.05) evidence of a carry-over effect on MMSE. Therefore, the analysis of treatment effect on MMSE was restricted to the first 12-week period. Treatment effect at 6 weeks was statistically significant (difference = 2.5 in favour of donepezil, 95% CI 0.1 to 5.0, p < 0.05). Treatment effect at 12 weeks was close, but not statistically significant (difference = 2.0 in favour of donepezil, 95% CI -0.1 to 4.5, p > 0.05). There were no statistically significant treatment effects on any of the five neuropsychological tests, except for digit span at 12 weeks (higher by 0.5 digits in favour of placebo, 95% CI 0.1 to 0.9). Gastrointestinal side effects occurred most frequently, affecting 13/18 subjects (72%), and

Enacting Subjectivities in Educational History: Methodological Reflections on the Use of Qualitative Interviews for History Writing

ERIC Educational Resources Information Center

Bjerg, Helle; Rasmussen, Lisa Rosen

2008-01-01

Two studies of the formation of pupils' subjectivities within the Danish school and educational system in the period 1945-2005 create the framework for a methodological discussion of how subjectivities in educational history can be studied. Both studies use qualitative interviews as a way of studying subject formations in educational history. This…

Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects.

PubMed

Darwish, Mona; Bond, Mary; Tracewell, William; Robertson, Philmore; Yang, Ronghua

2015-01-01

A hydrocodone extended-release (ER) formulation employing the CIMA(®) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release (IR) product. In this four-period crossover study, healthy subjects aged 18-45 years were randomized to receive a single intact, oral 45-mg tablet of one of three hydrocodone ER prototypes (low-, intermediate-, or high-level coating) or an intact, oral tablet of hydrocodone IR/acetaminophen (APAP) 10/325 mg every 6 h until four tablets were administered, with each of the four treatments administered once over the four study periods. Dosing periods were separated by a minimum 5-day washout. Naltrexone 50 mg was administered to block opioid receptors. Blood samples for pharmacokinetic assessments were collected predose and through 72 h postdose. Parameters assessed included maximum observed plasma hydrocodone concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)). Mean C(max) values were 49.2, 32.6, and 28.4 ng/mL for the low-, intermediate-, and high-level coating hydrocodone ER tablet prototypes, respectively, and 37.3 ng/mL for the hydrocodone IR/APAP tablet; respective median t(max) values were 5.9, 8.0, 8.0, and 1.0 h. Total systemic exposure to hydrocodone (AUC(0-∞)) was comparable between hydrocodone ER tablet prototypes (640, 600, and 578 ng·h/mL, respectively) and hydrocodone IR/APAP (581 ng·h/mL). No serious adverse events or deaths were reported. The most common adverse events included

Comparative Bioavailability and Tolerability of a Single 2-mg Dose of 2 Repaglinide Tablet Formulations in Fasting, Healthy Chinese Male Volunteers: An Open-Label, Randomized-Sequence, 2-Period Crossover Study☆

PubMed Central

Zhai, Xue-jia; Hu, Kai; Chen, Fen; Lu, Yong-ning

2013-01-01

Background Repaglinide, an oral insulin secretagogue, was the first meglitinide analogue to be approved for use in patients with type 2 diabetes mellitus. Objective In our study, the bioavailability and tolerability of the proposed generic formulation with the established reference formulation of repaglinide 2 mg were compared in a fasting, healthy Chinese male population. Methods This 2-week, open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in 22 healthy native Han Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 2-mg dose of the test or reference formulation, followed by a 7-day washout period and administration of the alternate formulation. After an overnight fast, subjects received a single oral dose of repaglinide (2 mg). Blood samples were drawn at predetermined time points (0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, and 6.0 hours). All plasma concentrations of repaglinide were measured by LC-MS/MS. The observed Cmax, Tmax, t1/2, and AUC were assessed. The formulations were to be considered bioequivalent if the ln-transformed ratios of Cmax and AUC were within the predetermined bioequivalence range of 80% to 125% established by the State Food and Drug Administration of the People’s Republic of China. Tolerability was assessed throughout the study via subject interview, vital signs, and blood sampling. Results The mean (SD) age of the subjects was 24.2 (2.3) years; their mean (SD) weight was 62.6 (5.8) kg, their mean (SD) height was 172 (5.7) cm, and their mean (SD) body mass index was 21.0 (1.1). The mean (SD) Cmax for repaglinide with the test and reference formulations were 20.0 (5.1) and 18.7 (8.7) ng/mL. The AUC0–t for the test formulation was 46.3 (15.1) and AUC0–∞ was 47.9 (16.5) ng•h/mL. With the reference formulation, the corresponding values were 46.4 (26.1) and 49.0 (31.3) ng•h/mL. The mean (SD) Tmax values with the test and reference

Comparative Bioavailability and Tolerability of a Single 2-mg Dose of 2 Repaglinide Tablet Formulations in Fasting, Healthy Chinese Male Volunteers: An Open-Label, Randomized-Sequence, 2-Period Crossover Study.

PubMed

Zhai, Xue-Jia; Hu, Kai; Chen, Fen; Lu, Yong-Ning

2013-12-01

Repaglinide, an oral insulin secretagogue, was the first meglitinide analogue to be approved for use in patients with type 2 diabetes mellitus. In our study, the bioavailability and tolerability of the proposed generic formulation with the established reference formulation of repaglinide 2 mg were compared in a fasting, healthy Chinese male population. This 2-week, open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in 22 healthy native Han Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 2-mg dose of the test or reference formulation, followed by a 7-day washout period and administration of the alternate formulation. After an overnight fast, subjects received a single oral dose of repaglinide (2 mg). Blood samples were drawn at predetermined time points (0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, and 6.0 hours). All plasma concentrations of repaglinide were measured by LC-MS/MS. The observed Cmax, Tmax, t1/2, and AUC were assessed. The formulations were to be considered bioequivalent if the ln-transformed ratios of Cmax and AUC were within the predetermined bioequivalence range of 80% to 125% established by the State Food and Drug Administration of the People's Republic of China. Tolerability was assessed throughout the study via subject interview, vital signs, and blood sampling. The mean (SD) age of the subjects was 24.2 (2.3) years; their mean (SD) weight was 62.6 (5.8) kg, their mean (SD) height was 172 (5.7) cm, and their mean (SD) body mass index was 21.0 (1.1). The mean (SD) Cmax for repaglinide with the test and reference formulations were 20.0 (5.1) and 18.7 (8.7) ng/mL. The AUC0-t for the test formulation was 46.3 (15.1) and AUC0-∞ was 47.9 (16.5) ng(•)h/mL. With the reference formulation, the corresponding values were 46.4 (26.1) and 49.0 (31.3) ng(•)h/mL. The mean (SD) Tmax values with the test and reference formulations were 1.2 (0.7) hours and 1

Period doubling in period-one steady states

NASA Astrophysics Data System (ADS)

Wang, Reuben R. W.; Xing, Bo; Carlo, Gabriel G.; Poletti, Dario

2018-02-01

Nonlinear classical dissipative systems present a rich phenomenology in their "route to chaos," including period doubling, i.e., the system evolves with a period which is twice that of the driving. However, typically the attractor of a periodically driven quantum open system evolves with a period which exactly matches that of the driving. Here, we analyze a periodically driven many-body open quantum system whose classical correspondent presents period doubling. We show that by studying the dynamical correlations, it is possible to show the occurrence of period doubling in the quantum (period-one) steady state. We also discuss that such systems are natural candidates for clean and intrinsically robust Floquet time crystals.

Development, glycolytic activity, and viability of preimplantation mouse embryos subjected to different periods of glucose starvation.

PubMed

Leppens-Luisier, G; Sakkas, D

1997-03-01

After compaction, the preimplantation mouse embryo switches to a glucose-based metabolism, whereas for the 2- to 4-cell stage embryo, glucose can be inhibitory. In this study, we investigated the adaptability of preimplantation embryos to different periods of glucose starvation by culturing in vitro fertilized (IVF) and in vivo-fertilized 1-cell OF1 mouse embryos. Blastocysts obtained from exposure to glucose starvation for different periods of time were examined for the number of cells in the trophectoderm and inner cell mass, and for glycolytic activity and viability. A high percentage of blastocysts was obtained when 1-cell embryos fertilized in vitro or in vivo were cultured in M16 until the 2-cell stage, were transferred to M16 without glucose (M16-G) until the 4- or 8-cell stage, and then were transferred to fresh M16-G. When in vivo-fertilized 1-cell embryos were cultured to the 2-cell stage and then left in M16, less than 5% formed blastocysts compared to 26% of those transferred into M16-G. Blastocysts obtained when in vivo-fertilized 1-cell embryos were left in M16-G after the 2-cell stage, however, showed a significantly elevated glycolytic activity compared to those transferred to fresh M16 or M16-G medium at the 4- or 8-cell stage. Interestingly, even though these embryos displayed elevated glycolytic activity, they did not exhibit differences in the numbers of inner cell mass and trophectoderm cells or in viability compared to embryos cultured according to other protocols. Blastocysts from all cultured protocols had a significantly lower total cell number and a lower trophectoderm, but not inner cell mass, cell number compared to blastocysts developed in vivo. This study documents the metabolic adaptability of the preimplantation embryo by highlighting its ability to proceed with development and retain viability when challenged with glucose starvation at different periods.

[Longitudinal follow-up of contact subjects of cases of tuberculosis in Paris].

PubMed

Fournier, A; Antoun, F; Charlois Ou, C; Muller, G; Ezri, L; Morin, P; Faure, A; Marteau, D; Keshtmand, H; Quelet, S

2015-09-01

To our knowledge, the proportion of active tuberculosis diagnosed after 12-18 months during a screening tuberculosis process in a specialized centre (centre de lutte antituberculeuse [CLAT]) has not been described in France. The majority of other countries do not have any recommendation to screen at this time. We evaluated the number of treated or not treated latent tuberculosis infections (LTI) identified during tuberculosis screening. We identified the causes of ITL non-treatment, the number of active disease cases and the proportion of subjects lost to follow-up after 12-18 months. Among the 1066 contact subjects, 159 (15 %) had a positive QuantiFERON-TB-Gold In-Tube(®) test. A prophylactic treatment with Rifinah(®) was given to 97 (61 %) subjects, 7 (7.3 %) having developed side effects that led to treatment interruption. A high proportion (56 %) of contact subjects were lost of follow-up and the main reason for no prophylactic treatment (20/52, 38 %) was due to these losses. No active disease cases were identified among the 474 (44 %) contact subjects who had a chest X-ray after 12-18 months follow-up by the CLAT. The low level of positive QuantiFERON-TB-Gold In-Tube(®) tests (15 %) could be explained by the high specificity of this test and the strong proportion of occupational contacts, of whom a probably significant number were not exposed to active disease. The absence of active disease at 12-18 months and a majority (56 %) of contact subjects lost from follow-up at this period let us propose not to recall contact subjects at 12-18 months with the exception of those living under the same roof as the index case and/or those having a cumulative contact time of greater than 100 hours during the theoretical infectious period. This proposal remains to be confirmed by other studies, particularly including possible secondary cases diagnosed outside the screening periods by the CLAT. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Reducing Operating Room Costs Through Real-Time Cost Information Feedback: A Pilot Study.

PubMed

Tabib, Christian H; Bahler, Clinton D; Hardacker, Thomas J; Ball, Kevin M; Sundaram, Chandru P

2015-08-01

To create a protocol for providing real-time operating room (OR) cost feedback to surgeons. We hypothesize that this protocol will reduce costs in a responsible way without sacrificing quality of care. All OR costs were obtained and recorded for robot-assisted partial nephrectomy and laparoscopic donor nephrectomy. Before the beginning of this project, costs pertaining to the 20 most recent cases were analyzed. Items were identified from previous cases as modifiable for replacement or omission. Timely feedback of total OR costs and cost of each item used was provided to the surgeon after each case, and costs were analyzed. A cost analysis of the robot-assisted partial nephrectomy before the washout period indicates expenditures of $5243.04 per case. Ten recommended modifiable items were found to have an average per case cost of $1229.33 representing 23.4% of the total cost. A postwashout period cost analysis found the total OR cost decreased by $899.67 (17.2%) because of changes directly related to the modifiable items. Therefore, 73.2% of the possible identified savings was realized. The same stepwise approach was applied to laparoscopic donor nephrectomies. The average total cost per case before the washout period was $3530.05 with $457.54 attributed to modifiable items. After the washout period, modifiable items costs were reduced by $289.73 (8.0%). No complications occurred in the donor nephrectomy cases while one postoperative complication occurred in the partial nephrectomy group. Providing surgeons with feedback related to OR costs may lead to a change in surgeon behavior and decreased overall costs. Further studies are needed to show equivalence in patient outcomes.

Comprehensive integrated spirometry using raised volume passive and forced expirations and multiple-breath nitrogen washout in infants

PubMed Central

Morris, Mohy G.

2009-01-01

With the rapid somatic growth and development in infants, simultaneous accurate measurements of lung volume and airway function are essential. Raised volume rapid thoracoabdominal compression (RTC) is widely used to generate forced expiration from an airway opening pressure of 30 cm H2O (V30). The (dynamic) functional residual capacity (FRCdyn) remains the lung volume most routinely measured. The aim of this study was to develop comprehensive integrated spirometry that included all subdivisions of lung volume at V30 or total lung capacity (TLC30). Measurements were performed on seventeen healthy infants aged 8.6–119.7 weeks. A commercial system for multiple-breath nitrogen washout (MBNW) to measure lung volumes and a custom made system to perform RTC were used in unison. A refined automated raised volume RTC and the following two novel single maneuvers with dual volume measurements were performed from V30 during a brief post-hyperventilation apneic pause: (1) the passive expiratory flow was integrated to produce the inspiratory capacity (IC) and the static (passive) FRC (FRCst) was estimated by initiating MBNW after end-passive expiration; (2) RTC was initiated late during passive expiration, flow was integrated to produce the slow vital capacity (jSVC) and the residual volume (RV) was measured by initiating MBNW after end-expiration while the jacket (j) was inflated. Intrasubject FRCdyn and FRCst measurements overlapped (p= 0.6420) but neither did with the RV (p<0.0001). Means (95% confidence interval) of FRCdyn, IC, FRCst, jSVC, RV, forced vital capacity and tidal volume were 21.2 (19.7–22.7), 36.7 (33.0–40.4), 21.2 (19.6–22.8), 40.7 (37.2–44.2), 18.1 (16.6–19.7), 40.7 (37.1–44.2) and 10.2 (9.6–10.7) ml/kg, respectively. Static lung volumes and capacities at V30 and variables from the best forced expiratory flow-volume curve were dependent on age, body length and weight. In conclusion, we developed a comprehensive physiologically

Comprehensive integrated spirometry using raised volume passive and forced expirations and multiple-breath nitrogen washout in infants.

PubMed

Morris, Mohy G

2010-02-28

With the rapid somatic growth and development in infants, simultaneous accurate measurements of lung volume and airway function are essential. Raised volume rapid thoracoabdominal compression (RTC) is widely used to generate forced expiration from an airway opening pressure of 30 cmH(2)O (V(30)). The (dynamic) functional residual capacity (FRC(dyn)) remains the lung volume most routinely measured. The aim of this study was to develop comprehensive integrated spirometry that included all subdivisions of lung volume at V(30) or total lung capacity (TLC(30)). Measurements were performed on 17 healthy infants aged 8.6-119.7 weeks. A commercial system for multiple-breath nitrogen washout (MBNW) to measure lung volumes and a custom made system to perform RTC were used in unison. A refined automated raised volume RTC and the following two novel single maneuvers with dual volume measurements were performed from V(30) during a brief post-hyperventilation apneic pause: (1) the passive expiratory flow was integrated to produce the inspiratory capacity (IC) and the static (passive) FRC (FRC(st)) was estimated by initiating MBNW after end-passive expiration; (2) RTC was initiated late during passive expiration, flow was integrated to produce the slow vital capacity ((j)SVC) and the residual volume (RV) was measured by initiating MBNW after end-expiration while the jacket (j) was inflated. Intrasubject FRC(dyn) and FRC(st) measurements overlapped (p=0.6420) but neither did with the RV (p<0.0001). Means (95% confidence interval) of FRC(dyn), IC, FRC(st), (j)SVC, RV, forced vital capacity and tidal volume were 21.2 (19.7-22.7), 36.7 (33.0-40.4), 21.2 (19.6-22.8), 40.7 (37.2-44.2), 18.1 (16.6-19.7), 40.7 (37.1-44.2) and 10.2 (9.6-10.7)ml/kg, respectively. Static lung volumes and capacities at V(30) and variables from the best forced expiratory flow-volume curve were dependent on age, body length and weight. In conclusion, we developed a comprehensive physiologically integrated

The Art of Projecting: The Cost of Keeping Periodicals.

ERIC Educational Resources Information Center

Ketcham, Lee; Born, Kathleen

1993-01-01

Provides periodical prices for 1993 and projects 1994 costs. Trends and projections, cost by country of origin, the role of foreign publications, currency fluctuations, and the basis for forecasting are discussed. Cost histories are given by subject area and country of publication. Prices of interest to smaller and public libraries are also given.…

Predictors of subjective health status 10 years post-PCI.

PubMed

van den Berge, Jan C; Dulfer, Karolijn; Utens, Elisabeth M W J; Hartman, Eline M J; Daemen, Joost; van Geuns, Robert J; van Domburg, Ron T

2016-06-01

Subjective health status is an increasingly important parameter to assess the effect of percutaneous coronary intervention (PCI) in clinical practice. Aim of this study was to determine medical and psychosocial predictors of poor subjective health status over a 10 years' post-PCI period. We included a series of consecutive PCI patients (n = 573) as part of the RESEARCH registry, a Dutch single-center retrospective cohort study. These patients completed the 36-item Short-Form Health Survey (SF-36) at baseline and 10 years post-PCI. We found 6 predictors of poor subjective health status 10 years post-PCI: SF-36 at baseline, age, previous PCI, obesity, acute myocardial infarction as indication for PCI, and diabetes mellitus (arranged from most to least numbers of sub domains). SF-36 scores at baseline, age, and previous PCI were significant predictors of subjective health status 10 years post-PCI. Specifically, the SF-36 score at baseline was an important predictor. Thus assessment of subjective health status at baseline is useful as an indicator to predict long-term subjective health status. Subjective health status becomes better by optimal medical treatment, cardiac rehabilitation and psychosocial support. This is the first study determining predictors of subjective health status 10 years post-PCI.

Period locking due to delayed feedback in a laser with saturable absorber.

PubMed

Carr, T W

2003-08-01

We consider laser with saturable absorber operating in the pulsating regime that is subject to delayed feedback. Alone, both the saturable absorber and delayed feedback cause the clockwise output to become unstable to periodic output via Hopf bifurcations. The delay feedback causes the laser pulse period to lock to an integer fraction of the feedback time. We derive a map from the original model to describe the periodic pulsations of the laser. Equations for the period of the laser predict the occurrence of the different locking states as well as the value of the pump when there is a switch between the locked states.

A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects.

PubMed

Costabile, Adele; Kolida, Sofia; Klinder, Annett; Gietl, Eva; Bäuerlein, Michael; Frohberg, Claus; Landschütze, Volker; Gibson, Glenn R

2010-10-01

There is growing interest in the use of inulins as substrates for the selective growth of beneficial gut bacteria such as bifidobacteria and lactobacilli because recent studies have established that their prebiotic effect is linked to several health benefits. In the present study, the impact of a very-long-chain inulin (VLCI), derived from globe artichoke (Cynara scolymus), on the human intestinal microbiota compared with maltodextrin was determined. A double-blind, cross-over study was carried out in thirty-two healthy adults who were randomised into two groups and consumed 10 g/d of either VLCI or maltodextrin, for two 3-week study periods, separated by a 3-week washout period. Numbers of faecal bifidobacteria and lactobacilli were significantly higher upon VLCI ingestion compared with the placebo. Additionally, levels of Atopobium group significantly increased, while Bacteroides-Prevotella numbers were significantly reduced. No significant changes in faecal SCFA concentrations were observed. There were no adverse gastrointestinal symptoms apart from a significant increase in mild and moderate bloating upon VLCI ingestion. These observations were also confirmed by in vitro gas production measurements. In conclusion, daily consumption of VLCI extracted from globe artichoke exerted a pronounced prebiotic effect on the human faecal microbiota composition and was well tolerated by all volunteers.

Values Education in Ottoman Empire in the Second Constitutional Period: A Sample Lesson

ERIC Educational Resources Information Center

Oruc, Sahin; Ilhan, Genc Osman

2015-01-01

Values education holds a significant place in an education environment and many studies are carried out about this new subject area. The aim of this study is to define how the subject of "values education" is handled in a sample lesson designed in the period of Constitution II in the Ottoman Empire. In this study, the lesson plan in the…

Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

PubMed

Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

2012-01-01

Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

Effect of Sugar-Free and Regular Toothpaste on Salivary Glucose and pH among Type 2 Diabetes- A Randomized Crossover Trial.

PubMed

Kapadia, Junaid; Dodamani, Arun; Baviskar, Priya; Karibasappa, G N; Pathak, Parag; Bezalwar, Abhishek

2017-07-01

Diabetes is one of the most prevalent diseases of mankind having general as well as oral health manifestations. Also, there is an increase of salivary glucose level in diabetic, inducing saccharolytic bacteria in saliva which can have adverse effects on oral tissue. To assess and compare the effect of sugar-free toothpaste on salivary glucose and pH among Type 2 diabetic and non-diabetic individuals. A randomized controlled-crossover study was carried out on 30 Type 2 diabetic (Group A) and 45 non-diabetic (Group B) subjects. In first half of study, subjects in Group A and Group B were intervened with sugar-free and regular toothpaste respectively. Salivary glucose and pH was assessed before and after brushing at interval of one week for a period of four weeks. In second half, toothpastes were switched over between the groups, after sufficient washout period. Salivary glucose and pH were assessed again in the same manner for both the groups. The data was subjected to paired t-test and unpaired t-test for intragroup and intergroup comparison respectively. Salivary glucose level was significantly reduced and salivary pH was increased significantly (p<0.001) in both groups with sugar free toothpaste when compared to regular toothpaste. Sugar free toothpaste showed beneficial effect on salivary glucose level and salivary pH level on diabetes and non-diabetes population.

Robotic therapy provides a stimulus for upper limb motor recovery after stroke that is complementary to and distinct from conventional therapy.

PubMed

Brokaw, Elizabeth B; Nichols, Diane; Holley, Rahsaan J; Lum, Peter S

2014-05-01

Individuals with chronic stroke often have long-lasting upper extremity impairments that impede function during activities of daily living. Rehabilitation robotics have shown promise in improving arm function, but current systems do not allow realistic training of activities of daily living. We have incorporated the ARMin III and HandSOME device into a novel robotic therapy modality that provides functional training of reach and grasp tasks. To compare the effects of equal doses of robotic and conventional therapy in individuals with chronic stroke. Subjects were randomized to 12 hours of robotic or conventional therapy and then crossed over to the other therapy type after a 1-month washout period. Twelve moderate to severely impaired individuals with chronic stroke were enrolled, and 10 completed the study. Across the 3-month study period, subjects showed significant improvements in the Fugl-Meyer (P = .013) and Box and Blocks tests (P = .028). The robotic intervention produced significantly greater improvements in the Action Research Arm Test than conventional therapy (P = .033). Gains in the Box and Blocks test from conventional therapy were larger than from robotic therapy in subjects who received conventional therapy after robotic therapy (P = .044). Data suggest that robotic therapy can elicit improvements in arm function that are distinct from conventional therapy and supplements conventional methods to improve outcomes. Results from this pilot study should be confirmed in a larger study.

One Egg per Day Improves Inflammation when Compared to an Oatmeal-Based Breakfast without Increasing Other Cardiometabolic Risk Factors in Diabetic Patients

PubMed Central

Ballesteros, Martha Nydia; Valenzuela, Fabrizio; Robles, Alma E.; Artalejo, Elizabeth; Aguilar, David; Andersen, Catherine J.; Valdez, Herlindo; Fernandez, Maria Luz

2015-01-01

There is concern that egg intake may increase blood glucose in patients with type 2 diabetes mellitus (T2DM). However, we have previously shown that eggs reduce inflammation in patients at risk for T2DM, including obese subjects and those with metabolic syndrome. Thus, we hypothesized that egg intake would not alter plasma glucose in T2DM patients when compared to oatmeal intake. Our primary endpoints for this clinical intervention were plasma glucose and the inflammatory markers tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). As secondary endpoints, we evaluated additional parameters of glucose metabolism, dyslipidemias, oxidative stress and inflammation. Twenty-nine subjects, 35–65 years with glycosylated hemoglobin (HbA1c) values <9% were recruited and randomly allocated to consume isocaloric breakfasts containing either one egg/day or 40 g of oatmeal with 472 mL of lactose-free milk/day for five weeks. Following a three-week washout period, subjects were assigned to the alternate breakfast. At the end of each period, we measured all primary and secondary endpoints. Subjects completed four-day dietary recalls and one exercise questionnaire for each breakfast period. There were no significant differences in plasma glucose, our primary endpoint, plasma lipids, lipoprotein size or subfraction concentrations, insulin, HbA1c, apolipoprotein B, oxidized LDL or C-reactive protein. However, after adjusting for gender, age and body mass index, aspartate amino-transferase (AST) (p < 0.05) and tumor necrosis factor (TNF)-α (p < 0.01), one of our primary endpoints were significantly reduced during the egg period. These results suggest that compared to an oatmeal-based breakfast, eggs do not have any detrimental effects on lipoprotein or glucose metabolism in T2DM. In contrast, eggs reduce AST and TNF-α in this population characterized by chronic low-grade inflammation. PMID:25970149

Fish oil-supplementation increases appetite in healthy adults. A randomized controlled cross-over trial.

PubMed

Damsbo-Svendsen, Signe; Rønsholdt, Mia Dybkjær; Lauritzen, Lotte

2013-07-01

Marine n-3 fatty acids are hypothesized to have beneficial effects on obesity and cancer cachexia possibly via an effect on appetite. The aim of this study was to investigate, if fish oil-supplementation affects appetite in healthy individuals. In a randomized cross-over study, 20 normal-weight subjects (50% females) were given ten 0.5-mL capsules/day of fish oil or soybean oil for 3 weeks separated by 1-week wash-out. In the end of each period, appetite was assessed by 10-cm visual analog scales immediately before and after a standardized breakfast. Results were analyzed in accordance with the paired design considering oil sequence and gender. All subjects completed both periods with a compliance of 96% and oil sequence did not affect the results. There was no difference between the two supplements in any pre-breakfast appetite scores, but the post-prandial sensation of being full was 1.21 cm (0.20; 2.22) lower after the fish oil-period. Furthermore, there was a supplement × gender-interaction on "desire to eat more" due to a score increase of 1.09 cm (0.28; 1.90) in women only. These results suggest that marine n-3 fatty acid may increase appetite. This finding would be potentially beneficial for patients with compromised nutritional status. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rectosigmoid stump washout as an alternative to permanent mucous fistula in patients undergoing subtotal colectomy for ulcerative colitis in emergency settings.

PubMed

Pellino, Gianluca; Sciaudone, Guido; Candilio, Giuseppe; Canonico, Silvestro; Selvaggi, Francesco

2012-01-01

Restorative proctocolectomy with ileopouch-anal anastomosis (IPAA) is the treatment of choice for intractable or complicated ulcerative colitis(UC). Elderly patients often present with acute colitis requiring emergent subtotal colectomy(SC). Frail patients are at risk of developing septic complications related to the closed rectosigmoidal stump, often requiring formation of a second stoma to be reversed at the time of completion proctectomy. This carries nuisance to such exhausted patients. We propose a simple and inexpensive trick to avoid the need for creating a mucous fistula. IPAA was performed as a 3-stage procedure in emergency settings. The rectosigmoidal stump was closed and placed subcutaneously; skin was closed over it. After SC, if patients showed signs of stump-related pelvic sepsis, a lavage of the rectal stump with povidone iodine solution and with saline was carried out as a rescue treatment aiming to avoid the need of opening the rectal stump to drain sepsis. Thirty-five patients underwent SC for UC between 1987 and 2012. The skin was closed over the closed stump in the 20. Seven patients out of these 20 experienced early stump-related septic complication. In five cases, we were able to avoid opening of the rectal stump, and a second stoma was unnecessary. After opening the closed stump in the remaining ones, a prompt improving of symptoms was observed. Rectal washout was well tolerated and avoided a second stoma in five out of seven patients, with better quality of life and body perception after IPAA surgery. This is relevant when dealing with geriatric patients, needing to completely recover before undergoing completion proctectomy.

Complementary role of parathormone washout test to 99mTc-MIBI parathyroid scintigraphy and histopathologic analysis of cell types in parathyroid adenomas.

PubMed

Ince, Semra; Emer, Ozdes; Deveci, Salih; Okuyucu, Kursat; Alagoz, Engin; San, Huseyin; Ayan, Aslı; Karacalioglu, Ozgur; Haymana, Cem; Gunalp, Bengul; Arslan, Nuri

2018-05-02

Parathyroid scintigraphy (PS) can be negative or equivocal (N/E) in a considerable number of cases with highly suspicious clinical findings and biochemical results for parathyroid adenoma (PA). The aims of this study were to investigate the complementary role of parathormone washout test (PWT) to PS in patients with primary hyperparathyroidism (PHPT) and evaluate histopathologic aspects of PAs in comparison with PS results. Thirty-eight patients with PHPT referred for PS were included in the study. Seventeen patients had both scintigraphic and ultrasonographic findings concordant with PA (Group A). Twenty-one patients having N/E PS, but suspected lesions for PA on ultrasonography (US) formed Group B. PWT was performed for all patients and they underwent the surgical intervention. An adenoma was removed in all patients and the histopathologic cell characteristics were established. The tumor size on US was larger in those patients whose adenomas were seen on the PS (P<.001). The percentages of chief (or principal), oxyphilic and clear cells in PAs were not statistically different between the groups. Serum parathormone level and PWT were not statistically significant between Group A and Group B (P=.095 and P=.04, respectively). Although there is not a definitive threshold value, the sensitivity of PS increases with lesion size. While chief cell and oxyphilic cell content of PAs tend to deplete in N/E PS, clear cell rate increases substantially. Combining PS with both US and PWT increases the sensitivity of detection and localization of PAs. Copyright © 2018. Publicado por Elsevier España, S.L.U.

Phase I clinical studies of the advanced glycation end-product (AGE)-breaker TRC4186: safety, tolerability and pharmacokinetics in healthy subjects.

PubMed

Chandra, Kumar P; Shiwalkar, Ajay; Kotecha, Jignesh; Thakkar, Purav; Srivastava, Ambrish; Chauthaiwale, Vijay; Sharma, Sanjay K; Cross, Maurice R; Dutt, Chaitanya

2009-01-01

-blind, placebo-controlled, single-dose, dose-ascending study in elderly male and female subjects at a dose of TRC4186 500 mg followed by TRC4186 1000 mg after a 7-day washout period. The safety and tolerability of TRC4186 were assessed by considering adverse events (AEs), ECG findings, vital signs and laboratory investigation results. TRC4186 was rapidly absorbed, with maximum plasma concentrations (C(max)) attained within 1-4 hours. C(max) and area under the plasma concentration-time curve (AUC) were dose proportional over the range 250-2500 mg for a single dose and 500-2000 mg for multiple doses with twice-daily administration. Steady-state conditions were attained within 6 days at different dose levels. C(max) and AUC were not affected by age, sex, race or type of formulation. The tablet formulation of TRC4186 was bioequivalent with the solution form of the drug under fasting conditions and systemic availability of the tablet formulation was reduced by 40% when administered under fed conditions. Terminal elimination and renal clearance in the elderly male (age 69.1 +/- 6.0 years) were not significantly different compared with younger subjects (age 31 +/- 8.6 years). TRC4186 was safe and well tolerated when administered orally with either a single or multiple doses across the different ages, sexes, races and formulations studied. A dose-proportional increase in plasma TRC4186 concentration was seen, with steady state being achieved within 6 days.

[Vaginitis and vaginosis. Comparison of two periods].

PubMed

Ceruti, M; Canestrelli, M; Piantelli, G; Amone, F; Condemi, V; De Paolis, P; Ludovici, G; Somenzi, P

1993-10-01

Vaginitis is the most frequent gynecological disease. It is characterized by objective and subjective signs of inflammation and differs from bacterial vaginosis (BV) which is an abnormal condition of the vaginal ecosystem caused by the excessive growth of aerobic and anaerobic flora normally present in the vagina with an increased risk of pelvic inflammatory disease (PID). The authors report the results of a study carried out at the Centre for Gynecological Infections at the Clinic of Obstetrics and Gynecology of the University of Parma. 828 patients were enrolled in the study during the period 1985-86 and 1559 patients during the two-year period 1991-92. The aim of the study was to evaluate variations in epidemiological data for vaginitis and bacterial vaginosis in the two periods examined. No significant changes were observed (p > 0.05) with regard to the prevalence of Ca, Tv and BV forms. On the other hand, there was a significant reduction (p < 0.001) in the forms sustained by other microorganisms (above all, streptococcus and enterobacteria) between the first and second periods with a parallel increase in the number of negative cases. The analysis of the age distribution of vaginitis and BV showed a reduction of other microorganisms and an increase in negative vaginal swabs in adults (> 20 years old).

[SEASONAL VARIATION OF MICROVOLT T-WAVE ALTERNANS IN PATIENTS WITH CARDIOVASCULAR DISEASE AND HEALTHY SUBJECTS].

PubMed

Halabi, Gh; Bulanova, N; Aleksandrova, S; Ivanov, G; Aleksandrova, M

2018-05-01

Objective - to access seasonal variation of microvolt T-wave alternans of ECG dispersion mapping in patients with cardiovascular disease and healthy subjects. ECG data of the three groups of healthy subjects have been compared: inhabitants of Beirut, Lebanon (n=51), inhabitants of Moscow, Russia (n=94) and ECG data of healthy subjects (n=44) from the testing ECG database of the PTB - The National Metrology Institute of Germany as well as a group of patients with cardiovascular disease (n=138), inhabitants of Beirut, Lebanon. Microvolt T-wave alternans of ECG dispersion mapping was evaluated in three points - Tbeginning, Tmaximum, Tend. In healthy subjects, the seasonal variation of ECG dispersion mapping microvolt T-wave alternans was nonexistent. Myocardial lesion is characterized by an increase in Tbeg, Tmax, Tend in relation to the healthy individuals. Tbeg values are minimal in winter and summer and increase in spring and autumn. Tend values were reversed - they were maximal in winter and summer, decreasing in spring-autumn period. Seasonal variation of Tmax - Tbeg, and Tmax -Tend was detected: Tmax - Tbeg increased in the winter-summer period and decreased in spring and autumn, Tmax-Tend - increased in the spring-autumn period in relation to the winter-summer period. In patients with cardiovascular disease, in contrast to the healthy, there is a seasonal variation in microvolt T-wave alternans of ECG dispersion mapping, with the maximum differences in the winter and spring seasons, which should be taken into account when applying the method in clinical practice.

Effects of salt supplementation on the albuminuric response to telmisartan with or without hydrochlorothiazide therapy in hypertensive patients with type 2 diabetes are modulated by habitual dietary salt intake.

PubMed

Ekinci, Elif I; Thomas, Georgina; Thomas, David; Johnson, Cameron; Macisaac, Richard J; Houlihan, Christine A; Finch, Sue; Panagiotopoulos, Sianna; O'Callaghan, Chris; Jerums, George

2009-08-01

OBJECTIVE This prospective randomized double-blind placebo-controlled crossover study examined the effects of sodium chloride (NaCl) supplementation on the antialbuminuric action of telmisartan with or without hydrochlorothiazide (HCT) in hypertensive patients with type 2 diabetes, increased albumin excretion rate (AER), and habitual low dietary salt intake (LDS; <100 mmol sodium/24 h on two of three consecutive occasions) or high dietary salt intake (HDS; >200 mmol sodium/24 h on two of three consecutive occasions). RESEARCH DESIGN AND METHODS Following a washout period, subjects (n = 32) received 40 mg/day telmisartan for 4 weeks followed by 40 mg telmisartan plus 12.5 mg/day HCT for 4 weeks. For the last 2 weeks of each treatment period, patients received either 100 mmol/day NaCl or placebo capsules. After a second washout, the regimen was repeated with supplements in reverse order. AER and ambulatory blood pressure were measured at weeks 0, 4, 8, 14, 18, and 22. RESULTS In LDS, NaCl supplementation reduced the anti-albuminuric effect of telmisartan with or without HCT from 42.3% (placebo) to 9.5% (P = 0.004). By contrast, in HDS, NaCl supplementation did not reduce the AER response to telmisartan with or without HCT (placebo 30.9%, NaCl 28.1%, P = 0.7). Changes in AER were independent of changes in blood pressure. CONCLUSIONS The AER response to telmisartan with or without HCT under habitual low salt intake can be blunted by NaCl supplementation. By contrast, when there is already a suppressed renin angiotensin aldosterone system under habitual high dietary salt intake, the additional NaCl does not alter the AER response.

Effects of Salt Supplementation on the Albuminuric Response to Telmisartan With or Without Hydrochlorothiazide Therapy in Hypertensive Patients With Type 2 Diabetes Are Modulated by Habitual Dietary Salt Intake

PubMed Central

Ekinci, Elif I.; Thomas, Georgina; Thomas, David; Johnson, Cameron; MacIsaac, Richard J.; Houlihan, Christine A.; Finch, Sue; Panagiotopoulos, Sianna; O'Callaghan, Chris; Jerums, George

2009-01-01

OBJECTIVE This prospective randomized double-blind placebo-controlled crossover study examined the effects of sodium chloride (NaCl) supplementation on the antialbuminuric action of telmisartan with or without hydrochlorothiazide (HCT) in hypertensive patients with type 2 diabetes, increased albumin excretion rate (AER), and habitual low dietary salt intake (LDS; <100 mmol sodium/24 h on two of three consecutive occasions) or high dietary salt intake (HDS; >200 mmol sodium/24 h on two of three consecutive occasions). RESEARCH DESIGN AND METHODS Following a washout period, subjects (n = 32) received 40 mg/day telmisartan for 4 weeks followed by 40 mg telmisartan plus 12.5 mg/day HCT for 4 weeks. For the last 2 weeks of each treatment period, patients received either 100 mmol/day NaCl or placebo capsules. After a second washout, the regimen was repeated with supplements in reverse order. AER and ambulatory blood pressure were measured at weeks 0, 4, 8, 14, 18, and 22. RESULTS In LDS, NaCl supplementation reduced the anti-albuminuric effect of telmisartan with or without HCT from 42.3% (placebo) to 9.5% (P = 0.004). By contrast, in HDS, NaCl supplementation did not reduce the AER response to telmisartan with or without HCT (placebo 30.9%, NaCl 28.1%, P = 0.7). Changes in AER were independent of changes in blood pressure. CONCLUSIONS The AER response to telmisartan with or without HCT under habitual low salt intake can be blunted by NaCl supplementation. By contrast, when there is already a suppressed renin angiotensin aldosterone system under habitual high dietary salt intake, the additional NaCl does not alter the AER response. PMID:19549737

Pharmacokinetics of detomidine following intravenous or oral-transmucosal administration and sedative effects of the oral-transmucosal treatment in dogs.

PubMed

Messenger, Kristen M; Hopfensperger, Marie; Knych, Heather K; Papich, Mark G

2016-04-01

To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs. 12 healthy adult dogs. In phase 1, detomidine was administered by IV (0.5 mg/m(2)) or OTM (1 mg/m(2)) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m(2)) or detomidine gel by OTM administration (0.5 mg/m(2)), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment. Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation. Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.

Absolute Bioavailability and Pharmacokinetics of Linezolid in Hospitalized Patients Given Enteral Feedings

PubMed Central

Beringer, Paul; Nguyen, Megan; Hoem, Nils; Louie, Stan; Gill, Mark; Gurevitch, Michael; Wong-Beringer, Annie

2005-01-01

Linezolid is a new antimicrobial agent effective against drug-resistant gram-positive pathogens which are common causes of infections in hospitalized patients. Many such patients rely on the intravenous or enteral route for nutrition and drug administration. Therefore, the bioavailability of linezolid administered enterally in the presence of enteral feedings in hospitalized patients was examined. Eighteen subjects were assessed in a randomized single-dose crossover study; 12 received continuous enteral feedings, while 6 did not (controls). Both groups received linezolid 600 mg intravenously and orally (control) or enterally, with the alternate route of administration separated by a 24-h washout period. Pharmacokinetic parameters derived from noncompartmental and compartmental analysis incorporating linear and nonlinear elimination pathways were compared between groups: F, Ka, Vs, K23, K32, Vmax, Km, and K20 (bioavailability, absorption rate constant, volume of central compartment normalized to body weight, intercompartmental rate constants, maximum velocity, Michaelis-Menten constant, and elimination rate constant, respectively). Pharmacokinetic (PK) data were available from 17 patients. The linezolid oral suspension was rapidly and completely absorbed by either the oral or enteral route of administration. Bioavailability was unaltered in the presence of enteral feedings. PK estimates remain similar regardless of the model applied. At the therapeutic dose used, only slight nonlinearity in elimination was observed. A linezolid oral suspension may be administered via the enteral route to hospitalized patients without compromise in its excellent bioavailability and rapid rate of absorption. Compartmental pharmacokinetic analysis offers a more flexible study application, since bioavailability (F) can be estimated directly with intermixed intravenous/oral doses without a need for a washout period. PMID:16127039

Pomegranate juice does not affect the disposition of simvastatin in healthy subjects.

PubMed

Park, Soo-Jin; Yeo, Chang-Woo; Shim, Eon-Jeong; Kim, Hyunmi; Liu, Kwang-Hyeon; Shin, Jae-Gook; Shon, Ji-Hong

2016-08-01

Previous in vitro and in vivo investigations reported controversial results for the inhibitory potential of pomegranate on Cytochrome P450 (CYP) 3A activity. This study evaluated the effect of pomegranate juice on the disposition of simvastatin, a CYP3A4 substrate, and simvastatin acid, its active metabolite, compared with grapefruit juice in healthy subjects. A single oral pharmacokinetic study of 40 mg simvastatin was conducted as a three-way crossover (control, pomegranate, and grapefruit juices) in 12 healthy male subjects. The subjects took pomegranate or grapefruit juice three times per day for 3 days (900 mL/day) and on the third day, the pharmacokinetic study was executed. Blood samples were collected to 24 h post-dose and the pharmacokinetic parameters of simvastatin and simvastatin acid were compared among the study periods. In the period of grapefruit juice, the mean C max and AUCinf of simvastatin [the geometric mean ratio (90 % CI) 15.6 (11.6-21.0) and 9.1 (6.0-13.7)] were increased significantly when compared with the control period, whereas they were not significantly different in the period of pomegranate juice [C max and AUCinf 1.20 (0.89-1.62) and 1.29 (0.85-1.94)]. The mean C max and AUCinf of simvastatin acid were increased significantly after intake of grapefruit juice, but not pomegranate juice. These results suggest that pomegranate juice affects little on the disposition of simvastatin in humans. Pomegranate juice does not seem to have a clinically relevant inhibitory potential on CYP3A4 activity.

Point-of-Purchase Price and Education Intervention to Reduce Consumption of Sugary Soft Drinks

PubMed Central

Chandra, Amitabh; McManus, Katherine D.; Willett, Walter C.

2010-01-01

Objectives. We investigated whether a price increase on regular (sugary) soft drinks and an educational intervention would reduce their sales. Methods. We implemented a 5-phase intervention at the Brigham and Women's Hospital cafeteria in Boston, Massachusetts. After posting existing prices of regular and diet soft drinks and water during baseline, we imposed several interventions in series: a price increase of 35% on regular soft drinks, a reversion to baseline prices (washout), an educational campaign, and a combination price and educational period. We collected data from a comparison site, Beth Israel Deaconess Hospital, also in Boston, for the final 3 phases. Results. Sales of regular soft drinks declined by 26% during the price increase phase. This reduction in sales persisted throughout the study period, with an additional decline of 18% during the combination phase compared with the washout period. Education had no independent effect on sales. Analysis of the comparison site showed no change in regular soft drink sales during the study period. Conclusions. A price increase may be an effective policy mechanism to decrease sales of regular soda. Further multisite studies in varied populations are warranted to confirm these results. PMID:20558801

Point-of-purchase price and education intervention to reduce consumption of sugary soft drinks.

PubMed

Block, Jason P; Chandra, Amitabh; McManus, Katherine D; Willett, Walter C

2010-08-01

We investigated whether a price increase on regular (sugary) soft drinks and an educational intervention would reduce their sales. We implemented a 5-phase intervention at the Brigham and Women's Hospital cafeteria in Boston, Massachusetts. After posting existing prices of regular and diet soft drinks and water during baseline, we imposed several interventions in series: a price increase of 35% on regular soft drinks, a reversion to baseline prices (washout), an educational campaign, and a combination price and educational period. We collected data from a comparison site, Beth Israel Deaconess Hospital, also in Boston, for the final 3 phases. Sales of regular soft drinks declined by 26% during the price increase phase. This reduction in sales persisted throughout the study period, with an additional decline of 18% during the combination phase compared with the washout period. Education had no independent effect on sales. Analysis of the comparison site showed no change in regular soft drink sales during the study period. A price increase may be an effective policy mechanism to decrease sales of regular soda. Further multisite studies in varied populations are warranted to confirm these results.

Periodic disorder along ramie cellulose microfibrils.

PubMed

Nishiyama, Yoshiharu; Kim, Ung-Jin; Kim, Dae-Young; Katsumata, Kyoko S; May, Roland P; Langan, Paul

2003-01-01

Small angle neutron scattering studies have been carried out on cellulose fibers from ramie and Populus maximowicii (cotton wood). Labile hydrogen atoms were replaced by deuterium atoms, in water-accessible disordered regions of the fibers, to increase the neutron scattering contrast between the disordered and crystalline regions. A meridional Bragg reflection, corresponding to a longitudinal periodicity of 150 nm, was observed when scattering collected from hydrogenated and deuterated dry ramie fibers was subtracted. No Bragg reflection was observed with the cotton wood fibers, probably because of lower orientation of the microfibrils in the cell wall. The ramie fibers were then subjected to electron microscopy, acid hydrolysis, gel permeation chromatography, and viscosity studies. The leveling off degree of polymerization (LODP) of the hydrolyzed samples matched exactly the periodicity observed in the diffraction studies. The weight loss related to the LODP was only about 1.5%, and thus, the microfibrils can be considered to have 4-5 disordered residues every 300 residues.

Dynamic 123I-BMIPP single-photon emission computed tomography in patients with congestive heart failure: effect of angiotensin II type-1 receptor blockade.

PubMed

Takeishi, Yasuchika; Minamihaba, Osamu; Yamauchi, Sou; Arimoto, Takanori; Hirono, Osamu; Takahashi, Hiroki; Akiyama, Hideyuki; Miyamoto, Takuya; Nitobe, Joji; Nozaki, Naoki; Tachibana, Hidetada; Okuyama, Masaki; Fukui, Akio; Kubota, Isao; Okada, Akio; Takahashi, Kazuei

2004-04-01

Heart failure is a major and growing public health problem with a high mortality rate. Although recent studies have demonstrated that a variety of metabolic and/or neurohumoral factors are involved in the progression of this syndrome, the precise mechanisms responsible for this complex condition are poorly understood. To examine 123I-beta-methyl-iodophenylpentadecanoic acid (BMIPP) kinetics in the early phase soon after tracer injection in patients with congestive heart failure (CHF), we performed dynamic single-photon emission computed tomography (SPECT). Twenty-six patients with CHF and eight control subjects were examined. The consecutive 15 images of 2-min dynamic SPECT were acquired for 30 min after injection. In the early phase after injection (0-4 min), a significant amount of radioactivity existed in the blood pool. After 6 min, the myocardial 123I-BMIPP image was clear and thus the washout rate of 123I-BMIPP from 6 to 30 min was calculated. The washout rate of 123I-BMIPP from the myocardium was faster in patients with CHF than in the controls (8 +/- 4 vs. -5 +/- 3%, p < 0.01). The washout rate of 123I-BMIPP demonstrated positive correlation with left ventricular (LV) end-diastolic volume index (R = 0.54, p < 0.02) and inverse correlation with LV ejection fraction (R = 0.53, p <0.02). Patients were given the angiotensin II type-1 receptor antagonist candesartan for 6 months, and dynamic SPECT was repeated. The enhanced washout rate of 123I-BMIPP in CHF was reduced after treatment with candesartan (p < 0.05). These data suggest that (1) enhanced washout of 123I-BMIPP was observed soon after injection in patients with CHF, (2) the activation of angiotensin II signaling pathway is involved as an intracellular mechanism for enhanced 123I-BMIPP washout in heart failure, and (3) improvement in fatty acid metabolism may represent a new mechanism for beneficial effects of angiotensin II receptor blockade on cardiac function and survival in patients with heart