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Healthy Volunteers (healthy + volunteer)
Kinds of Healthy Volunteers Selected AbstractsA Comparative Pharmacokinetic Study in Healthy Volunteers of the Effect of Carbamazepine and Oxcarbazepine on Cyp3a4EPILEPSIA, Issue 3 2007Astrid-Helene Andreasen Summary:,Purpose: Carbamazepine (CBZ) and oxcarbazepine (OXCZ) are well-known inducers of drug metabolism via CYP3A4. Indirect interaction studies and clinical experience suggest that CBZ has a stronger potential in this regard than OXCZ. However this has never been subject to a direct comparative study. We performed a study in healthy volunteers to investigate the relative inductive effect of CBZ and OXCZ on CYP3A4 activity using the metabolism of quinidine as a biomarker reaction. Methods: Ten healthy, male volunteers participated in an open, randomized crossover study consisting of two periods separated by a 4-week wash-out period. The subjects received 1200 mg oral OXCZ daily for 17 days and 800 mg oral CBZ for 17 days. A single 200 mg oral dose of quinidine was administered at baseline and following administration of CBZ and OXCZ. Outcome parameters were the formation clearance of 3-hydroxyquinidine dose and the ratio of the AUCs of 3-hydroxyquinidine to quinidine. Results: Formation clearance of 3-hydroxyquinidine was increased by means of 89% (CI: 36,164; p = 0.0022) and 181% (CI: 120,260, p < 0.0001) after treatment with OXCZ and CBZ, respectively, compared to baseline. The relative inductive effect of CBZ was 46% higher than for OXCZ. AUC ratio increased by means of 161% (CI: 139,187, p < 0.0001) (OXCZ) and 222% (CI: 192,257, p < 0.0001) (CBZ). Quinidine Cmax decreased by means of 29% (CI: 16,40, p = 0.0018) (OXCZ) and 33% (CI: 18,45, p = 0.0020) (CBZ). T½ decreased by means of 12% (CI: 6,17, p < 0.0014) (OXCZ) and 32% (CI: 25,38, p < 0.0001) (CBZ). tmax was not changed in either period. Conclusion: We confirm a clinically significant inductive effect of both OXCZ and CBZ. The inductive effect of CBZ was about 46% higher than that of OXCZ, a difference that may be of clinical relevance. [source] Influence of Colors on Habituation of Visual Evoked Potentials in Patients With Migraine With Aura and in Healthy VolunteersHEADACHE, Issue 1 2000J. Áfra MD Objective., To investigate whether colored glasses influence the habituation of visual evoked potentials. Background., We have previously shown that during pattern-reversal stimulations lasting 2 minutes the amplitude of the visual evoked potential increases in migraine with and without aura between attacks, whereas it decreases in healthy volunteers. Red light was found to increase visually evoked EEG fast activity only in children with migraine with aura. Wearing rose-tinted glasses for 4 months decreased attack frequency in parallel with a reduction of the visually evoked EEG fast activity. Methods., We compared the change in amplitude of the visual evoked potential using five different tinted glasses in 12 patients with migraine with aura and in 10 healthy volunteers. During continuous stimulation at 3.1 Hz, five blocks of 50 responses were sequentially averaged using red, yellow, green, blue, and grey glasses and without glasses in a random order and analyzed in terms of latencies and N1-P1 amplitudes. Amplitude changes were calculated for each block by comparison with the first block in every condition and analyzed statistically using Zerbe's method. Results., In healthy volunteers, the visual evoked potential amplitude increased with red glasses compared to without glasses (P=.05) or with green glasses (P=.03). In patients with migraine with aura, no significant difference was detected using colored glasses. Our findings in healthy volunteers are in line with earlier reports of increased excitability of the human visual cortex when exposed to red light. The lack of such a pattern in patients with migraine with aura suggests that the visual cortex is interictally hypoexcitable rather than hyperexcitable, which is consistent with studies of transcranial magnetic stimulation. [source] Intravenous Ethanol Infusions Can Mimic the Time Course of Breath Alcohol Concentrations Following Oral Alcohol Administration in Healthy VolunteersALCOHOLISM, Issue 5 2009Vijay A. Ramchandani Background:, Our previous studies have used intravenous (IV) clamping methods to demonstrate that family history positive (FHP) subjects exhibit a greater initial response to alcohol than family history negative (FHN) subjects. These results differ from other studies of family history of alcoholism (FHA) influences, most of which have used an oral alcohol challenge, suggesting that the route of administration may influence both the response to alcohol and FHA-related differences in response. To examine this possibility, one approach would be to directly compare responses following oral and IV alcohol administration in the same subjects. There is, however, a 3- to 4-fold variance, between- and within-subjects, in the breath alcohol concentrations (BrACs) following oral alcohol administration. Thus, our objective was to characterize the between-subject variability in the time course of BrACs following oral alcohol administration in healthy volunteers and to develop an IV infusion method to mimic the BrAC-time course attained following oral alcohol in the same subject. Methods:, This was a 2-session study in young adult, healthy, nondependent drinkers. In the first session, subjects ingested an oral dose of alcohol, based on total body water, to achieve a target peak BrAC of 80 mg%. In the second session, subjects received an IV infusion of ethanol designed to achieve the same BrAC time course as that achieved in the first session. The individualized infusion-rate profile was precomputed using a physiologically-based pharmacokinetic (PBPK) model for alcohol with model parameters adjusted to the individual's physiology. The peak BrACs (Cmax), times of peak BrAC (Tmax), and the areas under the BrAC vs. time curve (AUC) were compared between sessions to assess how closely the BrAC exposure during the IV infusion session mimicked the exposure following oral alcohol. Results:, The time course of BrACs following oral alcohol administration showed a high degree of between-subject variability. Mean Cmax, Tmax, and AUC did not differ by gender, indicating that calculation of oral doses based on total body water results in comparable BrAC-time courses, on average, for females and males. The IV infusion driven BrAC-time profiles demonstrated good fidelity to the BrAC-time curves resulting from oral alcohol: the mean %difference in Cmax and AUC were both 11%, while the mean %difference for Tmax was 27%. This degree of variability is less than half that seen across individuals following oral alcohol administration, which was substantial [coefficient of variation (%CV) ranging from 22 to 52%]. Conclusions:, Despite the use of standardized doses and controlled experimental conditions, there was substantial between-subject variability in the BrAC time course following oral administration of alcohol. The PBPK-model-based infusion method can mimic the BrACs attained with oral alcohol for individual subjects. This method provides a platform to evaluate effects attributable to the route of administration on the response to alcohol, as well as the influence of determinants such as family history of alcoholism on the alcohol response. [source] Inferior Vena Cava Percentage Collapse During Respiration Is Affected by the Sampling Location: An Ultrasound Study in Healthy VolunteersACADEMIC EMERGENCY MEDICINE, Issue 1 2010David J. Wallace MD Abstract Objectives:, Physicians are unable to reliably determine intravascular volume status through the clinical examination. Respiratory variation in the diameter of the inferior vena cava (IVC) has been investigated as a noninvasive marker of intravascular volume status; however, there has been a lack of standardization across investigations. The authors evaluated three locations along the IVC to determine if there is clinical equivalence of the respiratory percent collapse at these sites. The objective of this study was to determine the importance of location when measuring the IVC diameter during quiet respiration. Methods:, Measurements of the IVC were obtained during quiet passive respiration in supine healthy volunteers. All images were recorded in B-mode, with cine-loop adjustments in real time, to ensure that maximum and minimum IVC dimensions were obtained. One-way repeated-measures analysis of variance (ANOVA) was used for comparison of IVC measurement sites. Results:, The mean (±SD) percentage collapse was 20% (±16%) at the level of the diaphragm, 30% (±21%) at the level of the hepatic vein inlet, and 35% (±22%) at the level of the left renal vein. ANOVA revealed a significant overall effect for location of measurement, with F(2,35) = 6.00 and p = 0.006. Contrasts showed that the diaphragm percentage collapse was significantly smaller than the hepatic (F(1,36) = 5.14; p = 0.03) or renal caval index (F(1,36) = 11.85; p = 0.002). Conclusions:, Measurements of respiratory variation in IVC collapse in healthy volunteers are equivalent at the level of the left renal vein and at 2 cm caudal to the hepatic vein inlet. Measurements taken at the junction of the right atrium and IVC are not equivalent to the other sites; clinicians should avoid measuring percentage collapse of the IVC at this location. ACADEMIC EMERGENCY MEDICINE 2010; 17:96,99 © 2009 by the Society for Academic Emergency Medicine [source] Effects of Angelicae tenuissima radix, Angelicae dahuricae radix and Scutellariae radix Extracts on Cytochrome P450 Activities in Healthy VolunteersBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2009SoJeong Yi A total of 24 healthy male volunteers were assigned to one of three parallel herbal treatment groups, each consisting of eight volunteers. A cocktail of probe drugs for CYP enzymes was orally administered before and after multiple administrations of herbal medicines, three times a day for 13 days. Probe drugs used to measure CYP activities were caffeine (CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A4). The probe drugs and their metabolites were quantified in plasma or urine using HPLC or LC-MS/MS. Changes in each CYP activity was evaluated by metabolic ratio of the probe drug (concentration ratio of metabolite to parent form at reference time point) following the herbal medication period, compared to the baseline values. A. dahuricae radix significantly decreased CYP1A2 activity to 10% of baseline activity (95% CI: 0.05,0.21). S. radix also showed significant changes in CYP2C9 and CYP2E1 activities. Compared to baseline values, the metabolic activities of losartan were decreased to 71% (0.54,0.94). In addition, S. radix showed a 1.42-fold (1.03,1.97) increase in chlorzoxazone metabolic activity. However, CYP activities were not meaningfully influenced by A. tenuissima radix. Changes in certain CYP activities were observed after the administration of S. radix and A. dahuricae radix in healthy volunteers. Therefore, herbal medicines containing S. radix or A. dahuricae radix are candidates for further evaluation of clinically significant CYP-mediated herb-drug interactions in human beings. [source] Continuous glucose monitoring by intravenous microdialysisACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2010O. ROOYACKERS Background: The conflicting results from studies over tight glucose control in intensive care unit (ICU) patients ask for a continuous on-line real-time glucose monitoring in future. Here, intravenous microdialysis was tested in ICU patients and healthy volunteers. Primary aims were technical feasibility and accuracy. Methods: A microdialysis catheter was inserted into a peripheral vein. ICU patients (n=10) were studied for up to 5 days. Healthy volunteers (n=6) were studied on one occasion. Recordings were monitored during 70 min each 24-h period to allow for an estimate of variability over time. Microdialysis glucose and lactate were compared with plasma glucose and whole blood lactate. Results are presented as medians (quartiles) of the differences between microdialysis and plasma concentrations over each of the 70-min recording periods. Results: Out of the included ICU patients, no exclusions or early terminations were due to failure of the microdialysis catheter. The concordance was highly variable. The difference of medians over the recording periods differed by ,34% (,40, ,16) in patients and ,22% (,31, ,15) for the volunteers. In contrast, the overall variability within the individual measurement periods was low. Conclusion: Technical feasibility was good, but the accuracy was not sufficient and the variability between the recording periods was high without calibrations. The non-availability of suitable peripheral veins was a problem in many patients screened but not included in the study. Intravenous microdialysis to obtain continuous on-line real-time glucose monitoring is technically feasible, but accuracy needs to be improved. [source] Estimating Cardiorespiratory Fitness in Well-Functioning Older Adults: Treadmill Validation of the Long Distance Corridor WalkJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2006Eleanor M. Simonsick PhD Objectives: To determine criterion validity of the 400-m walk component of the Long Distance Corridor Walk (LDCW) and develop equations for estimating peak oxygen consumption (VO2) from 400-m time and factors intrinsic to test performance (e.g., heart rate (HR) and systolic blood pressure (SBP) response) in older adults. Design: Cross-sectional validation study. Setting: Gerontology Research Center, National Institute on Aging, Baltimore, Maryland. Participants: Healthy volunteers (56 men and 46 women) aged 60 to 91 participating in the Baltimore Longitudinal Study of Aging between August 1999 and July 2000. Measurements: The LDCW, consisting of a 2-minute walk followed immediately by a 400-m walk "done as quickly as possible" over a 20-m course was administered the day after maximal treadmill testing. HR and SBP were measured before testing and at the end of the 400-m walk. Weight, height, activity level, perceived effort, and stride length were also acquired. Results: Peak VO2 ranged from 12.2 to 31.1 mL oxygen/kg per minute, and 400-m time ranged from 2 minutes 52 seconds to 6 minutes 18 seconds. Correlation between 400-m time and peak VO2 was ,0.79. The estimating equation from linear regression included 400-m time (partial coefficient of determination (R2)=0.625), long versus short stride (partial R2=0.090), ending SBP (partial R2=0.019), and a correction factor for fast 400-m time (<240 seconds; partial R2=0.020) and explained 75.5% of the variance in peak VO2 (correlation coefficient=0.87). Conclusion: A 400-m walk performed as part of the LDCW provides a valid estimate of peak VO2 in older adults. Incorporating low-cost, safe assessments of fitness in clinical and research settings can identify early evidence of physical decline and individuals who may benefit from therapeutic interventions. [source] Pharmacodynamic differentiation of lorazepam sleepiness and dizziness using an ordered categorical measureJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2010Mohamed A. Kamal Abstract Categorical measures of lorazepam sleepiness and dizziness were modeled to identify differences in pharmacodynamic (PD) parameters between these adverse events (AEs). Differences in data-derived PD parameters were compared with relative incidence rates in the drug label (15.7% and 6.9%, respectively). Healthy volunteers (n,=,20) received single oral doses of 2,mg lorazepam or placebo in a randomized, double-blind, cross-over fashion. A seven-point categorical scale measuring the intensity of AEs was serially administered over 24,h. The maximum score (MaxS), and area under the effect curve (AUEC) were determined by noncompartmental methods and compared using a paired t -test. Individual scores were modeled using a logistic function implemented in NONMEM. AUEC and MaxS for sleepiness were significantly higher than dizziness (20.35 vs. 9.76, p,<,0.01) and (2.35 vs. 1.45, p,<,0.01). Model slope estimates were similar for sleepiness and dizziness (0.21,logits,×,mL/ng vs. 0.19,logits,×,mL/ng), but baseline logits were significantly higher for sleepiness (,2.81 vs. ,4.34,logits). Data-derived PD parameters were in concordance with label incidence rates. The higher intensity of sleepiness may be directly related to baseline (no drug present) while the increase in intensity as a result of drug was relatively similar for both AEs. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3628,3641, 2010 [source] Gelatin "Shots" as a New Method for Alcohol Administration in a Laboratory SettingALCOHOLISM, Issue 3 2006Elizabeth Ralevski Background: This experiment was designed to compare gelatin "shots",a new procedure for administering alcohol in a laboratory setting,to the alcohol beverage method. We proceeded to test whether the two methods were comparable in terms of alcohol absorption, metabolism, and effects on mood and whether gelatin "shots" were better than the beverage in disguising alcohol in a blind, placebo comparison. Methods: Healthy volunteers participated in a two-phase trial. In the first phase they completed 2 days of testing during which the effects of alcohol,delivered in beverage (1 day) or gelatin "shots" (alternative day),on blood and breathalyzer concentrations and mood were assessed. In the second phase participants completed 2 days of testing and were asked to identify if samples contained alcohol or placebo. The presentation of alcohol and placebo and the presentation of beverage or gelatin "shots" were random. Results: In the first phase there was a significant time-by-condition interaction in the blood alcohol concentration. Two-and-a-half hours after the alcohol was administered, those given gelatin "shots" had slightly lower but statistically significant blood alcohol concentrations. There was a significant time effect for breathalyzer alcohol levels but no condition or condition-by-time interaction. There were no differences between the two methods on any of the subjective mood measures. In the second phase of the study there were differences in the ability to differentiate alcohol from placebo between the two conditions with significantly more participants making errors in the gelatin "shots" than in the beverage condition. Conclusions: Our findings indicate that gelatin "shots" are an effective method for delivering alcohol to humans in a laboratory setting. This method may be superior to the alcohol beverage mixture in a placebo-controlled design because gelatin "shots" mask the alcohol much better than a beverage and are easier to administer. [source] Dual task interference in psychogenic tremorMOVEMENT DISORDERS, Issue 14 2007Hatice Kumru MD Abstract Psychogenic tremor (PT) is visually indistinguishable from voluntarily mimicked tremor. Healthy volunteers have difficulties with carrying out simultaneously two tasks due to the phenomenon known as dual task interference. Therefore, performing voluntary rhythmic movements would be a burden for carrying out fast ballistic movements with the contralateral hand. We hypothesized that, similarly to healthy volunteers performing rhythmic movements, patients with PT should show the effects of dual task interference, and this may distinguish them from patients with other types of tremor. We studied 6 patients with PT, 9 with Parkinson's disease (PD) and predominantly unilateral tremor, 11 with essential tremor (ET), and 10 normal volunteers (NV) mimicking tremor. They were requested to perform a unilateral simple reaction time task (SRT) to a visual imperative signal in two different conditions: at rest (rSRT) and during contralateral hand tremor (tSRT). Reaction time was significantly longer in tSRT than in rSRT in PT and in NV groups (P < 0.01 for both groups). However, no significant differences were observed between rSRT and tSRT in PD and ET. The delay of unilateral tSRT with respect to rSRT suggests an effect of tremorlike oscillatory movements on reaction time that is consistent with the concept of dual-task interference in NV or PT patients but not in PD or ET. These observations may be useful in the evaluation of psychogenic movement disorders. © 2007 Movement Disorder Society [source] Total body exposure to ultraviolet radiation does not influence plasma levels of immunoreactive ,-endorphin in manPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 6 2001Marjolein Wintzen Background/Aims: A growing number of reports support evidence of proopiomelanocortin (POMC)-derived peptides in human skin cells, although not consistently. Also the effect of ultraviolet radiation (UVR) on cutaneous and plasma levels of these POMC peptides has not been established unequivocally. We hypothesized that production of ,-endorphin (,E) may explain the sense of well-being many people experience when sun-bathing. The aim of the present study was to investigate whether exposure of the skin to UVR elevates plasma ,E. Method: Healthy volunteers (n=26) received a single, weighted dose of 15 J/cm2 of UVA. Several times during the hour following irradiation, plasma ,E- immunoreactivity (,E-IR) was determined by radioimmunoassay. The effect of repeated exposure wasassessed in 35 patients treated with UVB, UVA, or UVA-1. Plasma ACTH-IR was monitored in parallel. Results: Overall, plasma levels of ,E-IR and ACTH-IR showed no significant changes during the experiment, indicating that these peptides are not influenced by single or repeated exposures to UVR of different wavelengths. Conclusion: On the basis of these results, the skin does not appear to contribute significantly to the levels of circulating ,E or ACTH. These data offer no support for the hypothesis that exposure to UVR leads to an increased concentration of circulating ,E, which could contribute to the feeling of well-being that often accompanies sun-bathing. [source] Airways inflammation after exposure in a swine confinement building during cleaning procedureAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 4 2002Britt-Marie Larsson PhD Abstract Background Healthy volunteers exposed for 3 hr during weighing of pigs develop an airway inflammation characterized by a massive influx of neutrophilic granulocytes in the upper and lower airways and increased bronchial responsiveness to methacholine. The purpose of the present study was to investigate health effects from exposure during cleaning of the swine confinement building and to evaluate the effect of a respiratory protection device. Methods Sixteen subjects were exposed for 3 hr during cleaning of a swine confinement room with a high-pressure cleaner. Seven out of sixteen subjects were equipped with a mask during exposure. Results The bronchial responsiveness increased in all subjects following exposure, significantly more in the group exposed without a mask (P,<,0.05). The cell concentration (mainly neutrophilic granulocytes) in nasal lavage fluid as well as the concentration of interleukin-8, increased significantly only in those subjects exposed without a respiratory protection device. In peripheral blood, an increase of neutrophilic granulocytes was observed in both groups, although it was significantly higher in the group without mask (P,<,0.05). The inhalable dust level was 0.94 (0.74 , 1.55) mg/m3 and respirable dust 0.56 (0.51,0.63) mg/m3. Conclusion Exposure to dust aerosols during the cleaning of the interior of a swine confinement building induces increased bronchial responsiveness and an acute inflammatory reaction in the upper airways. The use of a mask attenuated but did not abolish the inflammatory response. This suggests that gases and/or ultrafine particles in this environment could be important factors in the development of increased bronchial responsiveness. Am. J. Ind. Med. 41:250,258, 2002. © 2002 Wiley-Liss, Inc. [source] Unilateral suppression of pharyngeal motor cortex to repetitive transcranial magnetic stimulation reveals functional asymmetry in the hemispheric projections to human swallowingTHE JOURNAL OF PHYSIOLOGY, Issue 2 2007Satish Mistry Inhibitory patterns of repetitive transcranial magnetic stimulation (rTMS) were applied to pharyngeal motor cortex in order to establish its role in modulating swallowing activity and provide evidence for functionally relevant hemispheric asymmetry. Healthy volunteers underwent single pulse TMS before and for 60 min after differing intensities of 1 Hz rTMS (n= 9, 6 male, 3 female, mean age 34 ± 3 years) or theta burst stimulation (TBS) (n= 9, 6 male, 3 female, mean age 37 ± 4 years). Electromyographic responses recorded from pharynx and hand were used as a measure of cortico-motor pathway excitability. Swallowing behaviour was then examined with a reaction time protocol, before and for up to 60 min after the most effective inhibitory protocol (1 Hz) applied to each hemisphere. Interventions were conducted on separate days and compared to sham using ANOVA. Only high intensity 1 Hz rTMS consistently suppressed pharyngeal motor cortex immediately and for up to 45 min (,34 ± 7%, P, 0.001). Adjacent hand and contralateral pharyngeal motor cortex showed no change in response (,15 ± 12%, P= 0.14 and 15 ± 12%, P= 0.45, respectively). When used to unilaterally disrupt each hemisphere, rTMS to pharyngeal motor cortex with the stronger responses altered normal (,12 ± 3%, P, 0.001) and fast (,9 ± 4%, P, 0.009) swallow times, not seen following rTMS to the contralateral cortex or after sham. Thus, suppression of pharyngeal motor cortex to rTMS is intensity and frequency dependent, which when applied to each hemisphere reveals functionally relevant asymmetry in the motor control of human swallowing. [source] Pharmacokinetics and pharmacodynamic effects of ABT-627, an oral ETA selective endothelin antagonist, in humansBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2000Marianne C. Verhaar Aims, Endothelins (ETs) may play a role in the pathogenesis of a variety of cardiovascular diseases. The present study was designed to investigate the pharmacokinetic and pharmacodynamic effects of the orally active ETA selective receptor antagonist ABT-627 in healthy humans. Methods, Healthy volunteers were included in two studies with cross-over design. Subjects received single or multiple dose (an 8 day period) administration of oralABT-627 or matched placebo, in a dose range of 0.2,40 mg. The pharmacokinetics of ABT-627 were described and its effects on systemic haemodynamics under resting conditions and on forearm vasoconstriction in response to ET-1 were assessed. Results, ABT-627 was generally well tolerated in both studies, with transient headache being the most reported adverse event (in 62%vs 4% during placebo, P < 0.05, for Study 1 and in 42%vs 60%, P = 0.2, for Study 2). ABT-627 was rapidly absorbed, reaching maximum plasma levels at ,,1 h post dose. Single dose ABT-627, at a dose of 20 and 40 mg, inhibited ET-1 induced forearm vasoconstriction at 8 h post dose. Eight days ABT-627 treatment, at a dose level of 5 mg and above, also effectively blocked forearm vasoconstriction to ET-1. ABT-627 caused a significant reduction in peripheral resistance as compared with placebo (16 ± 1 vs 19 ± 1, 18 ± 2 vs 23 ± 3, 15 ± 1 vs 17 ± 1 AU at 1, 5, 20 mg in Study 2) with only a mild decrease in blood pressure (79 ± 2 vs 84 ± 3, 80 ± 4 vs 90 ± 5, 75 ± 3 vs 79 ± 1 at 1, 5, 20 mg in Study 2). ABT-627 caused a moderate dose-dependent increase in circulating immunoreactive ET levels (a maximal increase of 50% over baseline at the 20 mg dose level). Conclusions, The oral ETA receptor blocker ABT-627 is well tolerated, rapidly absorbed, effectively blocks ET-1 induced vasoconstriction and causes a decrease in total peripheral resistance and mean arterial pressure. Our data suggest that ABT-627 may be a valuable tool in treatment of cardiovascular disease. [source] High-definition Fourier domain OCT: non-invasive assessment of BRB changesACTA OPHTHALMOLOGICA, Issue 2009R BERNARDES Purpose To demonstrate the possibility of using a non-invasive imaging technique, the high-definition spectral domain optical coherence tomography, as a surrogate detector of blood-retinal barrier (BRB) breakdown. Methods Healthy volunteers and diabetic patients with diabetic retinopathy, age- related macular degeneration, choroidal neo-vascularisation and cystoid macular edema, underwent optical coherence tomography by Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA, USA). Profiles of reflectivity distribution between the inner-limiting membrane and the retinal pigment epithelium were built, normalized, aligned and compared. Patients underwent retinal leakage analyzer (RLA) to identify areas of retinal fluorescein leakage into the vitreous as areas of blood-retinal barrier breakdown. Results The comparison between healthy volunteers' and patients' reflectivity distribution demonstrates these profiles differ. Moreover, when comparing reflectivity distribution within the same eye between areas of leakage and areas of non-leakage, the sum of the squared differences is over one decade relatively to the comparison between two similar areas (leakage/leakage or non-leakage/non-leakage). Conclusion These findings suggest that high-definition OCT may be useful in identifying areas of retinal leakage/BRB breakdown and therefore to be used as surrogate for fluorescein angiography and retinal leakage analyzer. [source] Immediate effect of benzalkonium chloride in decongestant nasal spray on the human nasal mucosal temperatureCLINICAL OTOLARYNGOLOGY, Issue 4 2004J. Lindemann Benzalkonium chloride is a preservative commonly used in nasal decongestant sprays. It has been suggested that benzalkonium chloride may be harmful to the nasal mucosa. Decongestion with the vasoconstrictor xylometazoline containing benzalkonium chloride has been shown to cause a significant reduction of the nasal mucosal temperature. The purpose of the present study was to determine the short-term influence of xylometazoline nasal spray with and without benzalkonium chloride on the nasal mucosal temperature. Healthy volunteers (30) were included in the study. Fifteen volunteers received xylometazoline nasal spray (1.0 mg/mL) containing benzalkonium chloride (0.1 mg/mL) and 15 age-matched subjects, received xylometazoline nasal spray without benzalkonium chloride. Using a miniaturized thermocouple the septal mucosal temperature was continuously measured at defined intranasal detection sites before and after application of the nasal spray. The mucosal temperature values did not significantly differ between the group receiving xylometazoline containing benzalkonium chloride and the group receiving xylometazoline spray without benzalkonium chloride before and after decongestion (P > 0.05). In both study groups septal mucosal temperatures significantly decreased after decongestion (P < 0.05) because of a reduction of the nasal mucosal blood flow following vasoconstriction. This study indicates that benzalkonium chloride itself does not seem to influence nasal blood flow and nasal mucosal temperature in topical nasal decongestants. [source] The Effect of Noise in the Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 7 2005Leslie S. Zun MD Abstract Background: It is hypothesized that high ambient noise in the emergency department (ED) adversely affects the ability of the examiner to hear heart and lung sounds. Objective: To determine the ability of various examiners to hear heart tones and lung sounds at the high end of loudness typically found in the ED setting. Methods: The study was divided into two parts. First, sound levels in the ED were measured over various times during the months of January through June 2001, using a sound level monitor. The second part of the study was the determination of the ability to hear heart and lung sounds on a young healthy volunteer using the same Littmann lightweight stethoscope at a predetermined ambient noise level of 90 dB. The results were entered into a database and analyzed using SPSS version 10 (Chicago, IL). Descriptive statistics, analysis of variance, frequencies, and correlation were calculated using this program. Results: Two hundred five sound measurements were taken in the ED during the study period in three locations at various hours. The mean noise level at the nursing station was 57.60 dB, with a minimum of 45.00 dB and a maximum of 70.00 dB. Four of the 104 test subjects (3.8%) were unable to hear the heart tones, and nine of the 104 (8.7%) were unable to hear the lung sounds. Fifty percent (27 of 54) of the test subjects reported diminished lung sounds and eight of 15 (53.3%) reported diminished heart sounds. No significant difference was found between hearing heart sounds and years of experience, age, professional position, and quality of the sound. Significant differences were found between hearing lung sounds and years of experience and professional position, but not with age, gender, and sound quality. Conclusions: This study demonstrated that most of the tested examiners have the ability to hear heart and lung sounds at the extreme of loudness found in one ED. [source] Rapid detection of Staphylococcus aureus by a combination of monoclonal antibody-coated latex and capillary electrophoresisELECTROPHORESIS, Issue 9 2006Peng Gao Abstract The rapid detection of pathogenic bacteria is extremely important in biotechnology and clinical diagnosis. CE has been utilized in the field of bacterial analysis for many years, but to some extent, simultaneous separation and identification of certain microbes from complex samples by CE coupled with UV detector is still a challenge. In this paper, we propose a new strategy for rapid separation and identification of Staphylococcus aureus (S.,aureus) in bacterial mixtures by means of specific mAb-coated latex coupled with CZE. An appropriate set of conditions that selectively isolated S.,aureus from the microorganisms Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae were established. S.,aureus could be differentiated from the others by unique peaks in the electropherograms. The validity was also confirmed by LIF with antibodies specific to both the latex and the microbial cells. The LOD is as low as 9.0×105 colony forming unit/mL. We have also utilized this technology to identify S.,aureus in a stool sample coming from a healthy volunteer spiked successfully with S.,aureus. This CZE-UV technique can be applied to rapid diagnosis of enteritis caused by S.,aureus or other bacterial control-related fields needing rapid identification of target pathogens from microbial mixtures. In theory, this method is suitable for the detection of any bacterium as long as corresponding bacterium-specific antibody-coated latex is available. [source] Enantioselective analysis of mirtazapine, demethylmirtazapine and 8-hydroxy mirtazapine in human urine after solid-phase microextractionJOURNAL OF SEPARATION SCIENCE, JSS, Issue 2 2010Fernando José Malagueño de Santana Abstract A selective and reproducible off-line solid-phase microextraction procedure was developed for the simultaneous enantioselective determination of mirtazapine (MRT), demethylmirtazapine and 8-hydroxymirtazapine in human urine. CE was used for optimization of the extraction procedure whereas LC-MS was used for method validation and application. The influence of important factors in the solid-phase microextraction efficiency is discussed, such as the fiber coatings, extraction time, pH, ionic strength, temperature and desorption time. Before extraction, human urine samples were submitted to enzymatic hydrolysis at 37°C for 16,h. Then, the enzyme was precipitated with trichloroacetic acid and the pH was adjusted to 8 with 1,mol/L pH 11 phosphate buffer solution. In the extraction, the analytes were transferred from the aqueous solution to the polydimethylsiloxane-divinylbenzene fiber coating and then desorbed in methanol. The mean recoveries were 5.4, 1.7 and 1.0% for MRT, demethylmirtazapine and 8-hydroxymirtazapine enantiomers, respectively. The method was linear over the concentration range of 62,1250,ng/mL. The within-day and between-day assay precision and accuracy were lower than 15%. The method was successfully employed in a preliminary cumulative urinary excretion study after administration of racemic MRT to a healthy volunteer. [source] A simple method for rectified noise floor suppression: Phase-corrected real data reconstruction with application to diffusion-weighted imagingMAGNETIC RESONANCE IN MEDICINE, Issue 2 2010Douglas E. Prah Abstract Diffusion-weighted MRI is an intrinsically low signal-to-noise ratio application due to the application of diffusion-weighting gradients and the consequent longer echo times. The signal-to-noise ratio worsens with increasing image resolution and diffusion imaging methods that use multiple and higher b-values. At low signal-to-noise ratios, standard magnitude reconstructed diffusion-weighted images are confounded by the existence of a rectified noise floor, producing poor estimates of diffusion metrics. Herein, we present a simple method of rectified noise floor suppression that involves phase correction of the real data. This approach was evaluated for diffusion-weighted imaging data, obtained from ethanol and water phantoms and the brain of a healthy volunteer. The parameter fits from monoexponential, biexponential, and stretched-exponential diffusion models were computed using phase-corrected real data and magnitude data. The results demonstrate that this newly developed simple approach of using phase-corrected real images acts to reduce or even suppress the confounding effects of a rectified noise floor, thereby producing more accurate estimates of diffusion parameters. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc. [source] Compressed sensing in hyperpolarized 3He Lung MRIMAGNETIC RESONANCE IN MEDICINE, Issue 4 2010Salma Ajraoui Abstract In this work, the application of compressed sensing techniques to the acquisition and reconstruction of hyperpolarized 3He lung MR images was investigated. The sparsity of 3He lung images in the wavelet domain was investigated through simulations based on fully sampled Cartesian two-dimensional and three-dimensional 3He lung ventilation images, and the k -spaces of 2D and 3D images were undersampled randomly and reconstructed by minimizing the L1 norm. The simulation results show that temporal resolution can be readily improved by a factor of 2 for two-dimensional and 4 to 5 for three-dimensional ventilation imaging with 3He with the levels of signal to noise ratio (SNR) (,19) typically obtained. The feasibility of producing accurate functional apparent diffusion coefficient (ADC) maps from undersampled data acquired with fewer radiofrequency pulses was also demonstrated, with the preservation of quantitative information (mean ADCcs , mean ADCfull , 0.16 cm2 sec,1). Prospective acquisition of 2-fold undersampled two-dimensional 3He images with a compressed sensing k -space pattern was then demonstrated in a healthy volunteer, and the results were compared to the equivalent fully sampled images (SNRcs = 34, SNRfull = 19). Magn Reson Med 63:1059,1069, 2010. © 2010 Wiley-Liss, Inc. [source] Fast CT-PRESS-based spiral chemical shift imaging at 3 TeslaMAGNETIC RESONANCE IN MEDICINE, Issue 5 2006Dirk Mayer Abstract A new sequence is presented that combines constant-time point-resolved spectroscopy (CT-PRESS) with fast spiral chemical shift imaging. It allows the acquisition of multivoxel spectra without line splitting with a minimum total measurement time of less than 5 min for a field of view of 24 cm and a nominal 1.5 × 1.5-cm2 in-plane resolution. Measurements were performed with 17 CS encoding steps in t1 (,t1 = 12.8 ms) and an average echo time of 151 ms, which was determined by simulating the CT-PRESS experiment for the spin systems of glutamate (Glu) and myo -inositol (mI). Signals from N-acetyl-aspartate, total creatine, choline-containing compounds (Cho), Glu, and mI were detected in a healthy volunteer with no or only minor baseline distortions within 14 min on a 3 T MR scanner. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source] Dynamic NMR spectroscopy of hyperpolarized 129Xe in human brain analyzed by an uptake modelMAGNETIC RESONANCE IN MEDICINE, Issue 4 2004Wolfgang Kilian Abstract Hyperpolarized 129Xe (HpXe) NMR not only holds promise for functional lung imaging, but for measurements of tissue perfusion as well. To investigate human brain perfusion, several time-series of 129Xe MR spectra were recorded from one healthy volunteer after HpXe inhalation. The time-dependent amplitudes of the MR spectra were analyzed by using a compartment model for xenon uptake modified to account for the loss of 129Xe polarization due to RF-excitation and for the breathhold technique used in the experiments. This analysis suggests that the resonances detected at 196.5 ± 1 ppm and 193 ± 1 ppm originate from HpXe dissolved in gray and white matter, respectively, and that T1 relaxation times of HpXe are different in gray and white matter (T1g > T1w). Magn Reson Med 51:843,847, 2004. © 2004 Wiley-Liss, Inc. [source] Characterization of boldione and its metabolites in human urine by liquid chromatography/electrospray ionization mass spectrometry and gas chromatography/mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 1 2006Yunje Kim Boldione (1,4-androstadiene-3,17-dione) is a direct precursor (prohormone) to the anabolic steroid boldenone (1,4-androstadiene-17,-ol-3-one). It is advertised as a highly anabolic/androgenic compound promoting muscularity, enhancing strength and overall physical performance, and is available on the Internet and in health stores. This work was undertaken to determine and characterize boldione and its metabolites in human urine, using both liquid chromatography with electrospray ionization mass spectrometry and gas chromatography with mass spectrometry and derivatization. Boldione and its three metabolites were detected in dosed human urine after dosing a healthy volunteer with 100,mg boldione. The excretion studies showed that boldione and its metabolites were detectable in urine for 48,h after oral administration, with maximum excretion rates after 1.8 and 3.6,h (boldenone case). The amounts of boldione and boldenone excreted in urine from this 100,mg dose were 34.45 and 15.95,mg, respectively. Copyright © 2005 John Wiley & Sons, Ltd. [source] Virtual Laryngoscopy: a Noninvasive Tool for the Assessment of Laryngeal Tumor ExtentTHE LARYNGOSCOPE, Issue 6 2007Yuling Yan PhD Abstract Objectives: Present a clinical application of virtual laryngoscopy (VL) in the assessment of laryngeal tumor and its extent. Study Design: CT data from two subjects are acquired for this preliminary study. One subject is a healthy volunteer and the other is a patient with laryngeal tumor. The laryngeal framework and upper airway are reconstructed using CT data, which allows for computer-aided internal and external anatomical views and interactive fly-through. Methods: These CT data are reconstructed into 0.5 mm slice images, resulting in a total of 200,300 image slices. An advanced commercial visualization software (AMIRA) is used for 3D image segmentation, reconstruction and surface rendering of laryngeal anatomical structures. Results: The 3D laryngeal framework and upper airway are reconstructed for both the tumor patient and the healthy subject. The conventional views of the reconstructed vocal folds are compared with those obtained from fiber-optic laryngoscope. Additionally, unique views of the vocal folds obtained from retrograde visualization and fly-through are presented, which are not possible to obtain using conventional endoscope imaging. The segmented anatomical model and the tumor from the patient's CT images were displayed individually to show the distribution of the tumor and its extent as well as spatial and contextual relationships to the larynx and airway anatomical structures. Conclusions: This study demonstrated the potential application of VL as a noninvasive clinical diagnostic tool for the assessment of laryngeal tumor and its extent. Our preliminary results demonstrated that the VL may provide valuable insights for the diagnosis and treatment planning for laryngeal and airway tumors. The noninvasive VL may complement the invasive laryngoscopic examinations for the staging of tumors and follow-ups on surgical interventions. [source] ORIGINAL ARTICLE: The ability of anaesthetists to identify the position of the right internal jugular vein correctly using anatomical landmarksANAESTHESIA, Issue 9 2010C. R. Harber Summary We performed a study of 85 consenting anaesthetists to assess their ability to locate the right internal jugular vein using a landmark technique. Initially, a questionnaire was completed ascertaining previous user experience. An ultrasound probe, using the midpoint as an ,imaginary needle', was placed on the neck of a healthy volunteer (with previously confirmed normal anatomy) and the image recorded. Both anaesthetist and volunteer were blinded to the screen until the image was stored. Anaesthetists were grouped into those in training before 2002 (Pre-2002, n = 58), when National Institute for Health and Clinical Excellence guidelines recommending ultrasound guidance were published, and those training after this time point (Post-2002, n = 27). The success rate for identifying the internal jugular vein using the landmark technique was 36/58 (62%) in the Pre-2002 group and 6/27 (22%) in the Post-2002 group (p < 0.001). Three participants in each group would have hit the carotid artery (5% Pre-2002 and 11% Post-2002 respectively; p = 0.2). The advent of routine use of ultrasound has resulted in a cohort of anaesthetists who are unable to use a landmark technique effectively or safely. This has significant training implications. [source] Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary resultsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2008Beatriz Bicalho Abstract Dihydroergotoxine is a mixture of semi-synthetic ergot alkaloids mainly used for age-related cognitive impairment. In this study, dihydroergotoxine (30,µM) was added to incubates of rat and bovine liver microsomes, and the resulting major metabolites were identified as hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine on the basis of molecular mass measurements, determined with a time-of-flight mass spectrometer. The relevance of these to humans was then investigated by simultaneously monitoring dihydroergotoxine and its hydroxy-metabolites in human plasma by LC-MS/MS after oral dosing of dihydroergotoxine mesylate (27,mg) to a healthy volunteer (male, age 45, height 1.93,m, weight 103,kg). In this preliminary approach, the peaks (Cmax) of dihydroergocornine, dihydroergocryptine and dihydroergocristine were about 0.04,µg/l. The peaks (Cmax) of their hydroxy-metabolites were 0.98, 0.53 and 0.30,µg/l, respectively. In conclusion, in this preliminary approach it was found that hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine were one order of magnitude higher in concentration than their parents in human plasma. Copyright © 2007 John Wiley & Sons, Ltd. [source] Population modelling of the effect of inogatran, at thrombin inhibitor, on ex vivo coagulation time (APTT) in healthy subjects and patients with coronary artery diseaseBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2001Marie Cullberg Aims, The purpose of this study was to characterize the relationship between the degree of anticoagulation, assessed by APTT, and the plasma concentration of inogatran in healthy subjects and in patients with coronary artery disease. Methods, Data from five phase I studies in 78 healthy males and two phase II multicentre studies in 948 patients of both sexes with unstable angina pectoris or non-Q-wave myocardial infarction were evaluated. A total of 3296 pairs of concentration-APTT samples were obtained before, during, and after intravenous infusions of inogatran. Mixed effects modelling was used for population pharmacodynamic analysis of the drug effect and for describing the variability in baseline APTT. Results, The population mean baseline APTT was 29 s, but large variations between individuals (s.d. 3.6 s) were observed. The variability between studies (1.3 s) and centres (1.8 s) were of less importance, though statistically significant. APTT increased in a nonlinear manner with increasing inogatran concentration and the relationship was well described by a combined linear and Emax model. A significant part of the overall variability could be ascribed to the APTT reagent and equipment used at the different study centres. These method-dependent differences were compensated for by including the lower limit of the normal reference range as a covariate, affecting both baseline and Emax, in the model. For the typical healthy subject and patient, the method-corrected population mean parameters were: APTTbaseline 35 and 31 s, slope 8.0 and 5.8 s l µmol,1, Emax 36 and 34 s, and EC50 0.54 and 0.72 µmol l,1, respectively. The model predicted plasma concentration needed to double the APTT from the baseline value was 1.25 and 1.45 µmol l,1 in the healthy volunteer and patient, respectively. Conclusions, The nonlinear relationship between APTT and inogatran concentration in plasma was well described by a combined linear and Emax model. Pooling of data was made possible by incorporating a centre-specific characteristic of the assay method in the model. Patients had lower baseline APTT and appeared to have less pronounced effect of inogatran than young healthy subjects. [source] Identifying Left Ventricular Dysfunction in Pulmonary HypertensionCONGESTIVE HEART FAILURE, Issue 5 2009Navin Rajagopalan MD The significance of left ventricular (LV) dysfunction in patients with pulmonary hypertension (PH) is unknown. Our purpose was to quantify LV function in PH patients by measuring LV myocardial performance index (MPI) and correlating it with invasively determined hemodynamic variables. The authors prospectively measured LV MPI via transthoracic echocardiography in 50 patients with PH (53±11 years; 35 women) who also underwent right heart catheterization within 1 day of echocardiography. For comparative purposes, LV MPI was also measured in 15 healthy volunteers who served as controls. LV MPI was significantly increased in the PH group compared with controls (0.62±0.27 vs 0.36±0.08; P<.001), indicating worse LV dysfunction despite that LV ejection fraction was not significantly different between the groups (58%±4% vs 60%±3%). LV MPI demonstrated significant correlations with invasively determined mean pulmonary artery pressure (r=.50; P<.001), pulmonary vascular resistance (r=.57; P<.001), and cardiac index (r=,.64; P<.001). By receiver operating characteristic analysis, LV MPI >0.75 predicted cardiac index <2 L/min/m2 with 89% sensitivity and 78% specificity (area under the curve, 0.89). In a multivariate model, LV MPI was independently associated with cardiac index (P<.01). Patients with PH demonstrate abnormal LV function as quantified by elevated LV MPI, which correlates significantly with pulmonary vascular resistance and cardiac index. [source] Monitoring Lung Resistivity Changes in Congestive Heart Failure Patients Using the Bioimpedance TechniqueCONGESTIVE HEART FAILURE, Issue 6 2005Sharon Zlochiver MSc The feasibility of a novel, dedicated system for monitoring lung resistivity in congestive heart failure patients, implementing a hybrid approach of the bioimpedance technique, was assessed in this preliminary study. Thirty-three healthy volunteers and 34 congestive heart failure patients were measured with the PulmoTrace system (Cardiolnspect, Tel Aviv University, Tel Aviv, Israel) during tidal respiration, and the ability to monitor the respective lung resistivity values was assessed. Mean left and right lung resistivity values of 1205±163 and 1200±165 ,·cm for the control group and 888±193 and 943±187 ,·cm for the congestive heart failure group were found, indicating a significant (p<2·10,7) difference between the two groups. The results of long-term monitoring of two patients during medical treatment are also shown. This hybrid approach system is believed to improve diagnostic capabilities and help physicians to better adjust medication dosage on a frequent basis. [source] | |||||||||||||||||||||||||||||||||||||||||||