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Healthy Adults (healthy + adult)
Kinds of Healthy Adults Terms modified by Healthy Adults Selected AbstractsCircadian and Gender Effects on Repolarization in Healthy Adults: A Study Using Harmonic Regression AnalysisANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2010Kenneth A. Mayuga M.D. Background: Sudden cardiac death and myocardial infarction have a circadian variation with a peak incidence in the early morning hours. Increased dispersion of repolarization facilitates the development of conduction delay necessary to induce sustained arrhythmia. Both QT-dispersion and T-wave peak to T-wave end (TpTe) have been proposed as markers of dispersion of myocardial repolarization. Methods: Forty healthy adults (20 women), age 35,67 years old, with normal EKGs, echocardiograms, stress tests, and tilt-table tests were analyzed during a 27-hour hospital stay. EKGs were done at eight different time points. QT-intervals, QT-dispersion, and TpTe were measured at each time point. Harmonic regression was used to model circadian periodicity, P < 0.05 was considered significant. Results: The composite QT-interval was longer in women than in men (416 ± 17 msec vs 411 ± 20 msec, respectively, P = 0.006). The QT-dispersion among all leads was greater in men than women (37 ± 13 msec vs 30 ± 11 msec, respectively, P < 0.0001); a similar difference was found in the precordial leads. Harmonic regression showed that QT-dispersion had a significant circadian variation, primarily in men. In men, the maximum QT-dispersion occurred at 6 AM (45 ± 15 msec). TpTe also had a significant circadian variation that was not affected by gender in the majority of leads. Conclusions: A circadian variation exists in the dispersion of myocardial repolarization, as measured by both TpTe and QT-dispersion. Men and women have a different circadian variation pattern. Further studies regarding the mechanisms and clinical implications are needed. Ann Noninvasive Electrocardiol 2010;15(1):3,10 [source] Sensory acceptability of white bread with added Australian sweet lupin (Lupinus angustifolius) kernel fibre and its glycaemic and insulinaemic responses when eaten as a breakfastJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 13 2003Stuart K Johnson Abstract The aim of this study was to determine whether lupin kernel fibre (LKF) could lower the glycaemic and insulinaemic responses of bread without reducing palatability. Healthy adults (n = 21) consumed control (white) bread (2.7% total dietary fibre (TDF)) once and LKF bread (8.5% TDF) once, as 50 g available carbohydrate breakfasts, in random order on different occasions. Venous blood samples were taken fasting, then post-prandially over 2 h and analysed for plasma glucose and insulin. Incremental areas under curves (IAUC) for glucose and insulin, glycaemic index (GI) and insulinaemic index (II) were calculated. Sensory acceptability of a control (white) bread (3.5% TDF) and two LKF breads (6.6 and 8.3% TDF) was determined (n = 54). A reduction of 18.8% (P < 0.05) was seen in IAUC for insulin of LKF bread compared with the control (white) bread breakfast. No significant differences were seen in the other glucose or insulin measures. Mean sensory ratings for all breads were ,acceptable', with no significant differences between the ratings of the breads. In conclusion, LKF can be formulated into palatable bread and beneficially influenced the IAUC for insulin. Further studies are required to determine unequivocally whether LKF has beneficial effects on blood glucose and insulin measures. Copyright © 2003 Society of Chemical Industry [source] An Open Randomized Study of Inactivated Hepatitis A Vaccine Administered Concomitantly with Typhoid Fever and Yellow Fever VaccinesJOURNAL OF TRAVEL MEDICINE, Issue 2 2002Elaine C. Jong Background: Concomitant administration of several vaccines is a common practice when travel clinics prepare persons for international travel. The purpose of the study was to compare the immunogenicity and safety of hepatitis A, typhoid fever, and yellow fever vaccines administered concomitantly with hepatitis A vaccine administered alone and typhoid fever and yellow fever vaccines administered alone. Methods: Healthy adults 18 to 55 years of age were randomized to receive either VAQTA, TyphimVi, and YF-VAX on day 0 and VAQTA at week 24 (Group 1); TyphimVi and YF-VAX on day 0 and an optional dose of VAQTA 1 month later (Group 2); or VAQTA at day 0 and week 24 (Group 3). Results: From March to December 1997, a total of 240 subjects were enrolled, 80 in each treatment group. Most were female and Caucasian, and the mean age was 29.4 years. Four weeks after vaccine dose 1, seroconversion to protective antibody levels against hepatitis A was 95.9% in Group 1 and 100% in Group 3. In Group 1, 93.4% of subjects demonstrated at least a 4-fold rise in neutralizing antibody levels against typhoid, compared with 90% in Group 2. Serum neutralizing antibody against yellow fever developed in 98.6% of subjects in Group 1 compared with 100% in Group 2. Conclusions: These findings were consistent with similarity in the immune responses between treatment groups as defined a priori. The adverse experience (AE) profile did not appear to be substantially affected by concomitant administration of all three vaccines. Providing these three vaccines concomitantly can simplify the process of obtaining pretravel prophylaxis and may help ensure that all needed vaccines are administered. [source] Casual Chocolate Consumption and Inhibition of Platelet FunctionPREVENTIVE CARDIOLOGY, Issue 4 2007Bryan Bordeaux DO Observational studies have associated reduced cardiovascular mortality with chocolate consumption. Feeding studies of high-dose, flavanol-rich chocolate show antiplatelet effects, but the effect of casual chocolate consumption on platelet function is unknown. Healthy adults (N=1535) were proscribed from consuming foods affecting platelet function, including chocolate, for 48 hours and completed a 24-hour dietary recall before ex vivo platelet testing with the Platelet Function Analyzer (PFA)-100 (Dade Behring, Inc, Deerfield, IL) test and in vivo testing with urinary 11-dehydro thromboxane B2 (Tx-M) measurements. Some participants (n=141) reported ignoring the prohibition of consuming chocolate before platelet testing. Despite having similar baseline characteristics, chocolate consumers had longer PFA closure times (130 vs 123 seconds, P=.005) and decreased Tx-M levels (175 vs 290 ng/mol creatinine, P=.03). Chocolate remained a significant independent predictor of both ex vivo and in vivo platelet function testing after adjusting for confounders. The authors concluded that even consuming modest amounts of commercial chocolate has important antiplatelet effects. [source] Mindfulness-based stress reduction and attentional controlCLINICAL PSYCHOLOGY AND PSYCHOTHERAPY (AN INTERNATIONAL JOURNAL OF THEORY & PRACTICE), Issue 6 2007Nicole D. Anderson This study was designed to test the hypothesis that mindfulness involves sustained attention, attention switching, inhibition of elaborative processing and non-directed attention. Healthy adults were tested before and after random assignment to an 8-week Mindfulness-Based Stress Reduction (MBSR) course (n = 39) or a wait-list control (n = 33). Testing included measures of sustained attention, attention switching, Stroop interference (as a measure of inhibition of elaborative processing), detection of objects in consistent or inconsistent scenes (as a measure of non-directed attention), as well as self-report measures of emotional well-being and mindfulness. Participation in the MBSR course was associated with significantly greater improvements in emotional well-being and mindfulness, but no improvements in attentional control relative to the control group. However, improvements in mindfulness after MBSR were correlated with improvements in object detection. We discuss the implications of these results as they relate to the role of attention in mindfulness.,Copyright © 2007 John Wiley & Sons, Ltd. [source] Cutaneous abscess by Trichosporon asahii developing on a steroid injection site in a healthy adultCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2006S. J. Yun Summary We report a rare case of cutaneous abscess by Trichosporon asahii in an immunocompetent adult. A 31-year-old Korean woman presented to our hospital with a cutaneous abscess. She had received an intralesional steroid injection 4 months earlier on the site of a hypertrophic scar. Direct sequencing of the intergenic spacer regions of the rRNA genes identified T. asahii. The decreased local immunity after the steroid injection might have triggered the infection by T. asahii. A cutaneous abscess formation by T. asahii in an immunocompetent patient is an unusual cutaneous finding that to our knowledge has not been reported previously. The local immune reaction of the skin is important for the prevention of Trichosporon infection. [source] Human peripheral blood B-cell compartments: A crossroad in B-cell traffic,CYTOMETRY, Issue S1 2010M. Perez-Andres Abstract A relatively high number of different subsets of B-cells are generated through the differentiation of early B-cell precursors into mature B-lymphocytes in the bone marrow (BM) and antigen-triggered maturation of germinal center B-cells into memory B-lymphocytes and plasmablasts in lymphoid tissues. These B-cell subpopulations, which are produced in the BM and lymphoid tissues, recirculate through peripheral blood (PB), into different tissues including mucosa and the BM, where long-living plasma cells produce antibodies. These circulating PB B-cells can be classified according to their maturation stage into i) immature/transitional, ii) naïve, and iii) memory B-lymphocytes, and iv) plasmablasts/plasma cells. Additionally, unique subsets of memory B-lymphocytes and plasmablasts/plasma cells can be identified based on their differential expression of unique Ig-heavy chain isotypes (e.g.: IgM, IgD, IgG, IgA). In the present paper, we review recent data reported in the literature about the distribution, immunophenotypic and functional characteristics of these cell subpopulations, as well as their distribution in PB according to age and seasonal changes. Additional information is also provided in this regard based on the study of a population-based cohort of 600 healthy adults aged from 20 to 80 years, recruited in the Salamanca area in western Spain. Detailed knowledge of the distribution and traffic of B-cell subsets through PB mirrors the immune status of an individual subject and it may also contribute to a better understanding of B-cell disorders related to B-cell biology and homeostasis, such as monoclonal B-cell lymphocytosis (MBL). © 2010 International Clinical Cytometry Society [source] Oestrogen receptor , is expressed in adult human skeletal muscle both at the mRNA and protein levelACTA PHYSIOLOGICA, Issue 4 2003A. Wiik Abstract Aim:, There are two known oestrogen receptors (ER), oestrogen receptor , (ER,) and the recently cloned oestrogen receptor , (ER,). ER, mRNA has been detected in mouse, rat, bovine and human skeletal muscle. ER, mRNA has been detected in bovine skeletal muscle. To our knowledge, no study has investigated the expression of oestrogen receptor , in human skeletal muscle. Therefore, the primary aim of the present investigation was to study ER, mRNA and protein expression in human skeletal muscle. In addition the ER, expression was also studied. Methods:, Muscle biopsies were taken from vastus lateralis in six healthy adults (three women and three men). mRNA expression was detected with real-time PCR (TaqMan) and protein localization by immunohistochemistry. Results:, A clear expression of ER, and ER, mRNA was seen in skeletal muscle in all subjects. The ER, mRNA expression was 180 fold higher compared with that of ER, mRNA. Immunohistochemistry demonstrated positive staining for ER,, but not for ER,, with localization to the nuclei of skeletal muscle fibres. On average, 70% of all nuclei were ER, -positive. Conclusion:, The present study shows for the first time ER, mRNA and protein expression in human skeletal muscle tissue in both males and females. [source] The stability of correlates of labour force activityACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2009G. Waghorn Objective:, To investigate the stability of correlates of labour force activity among people with affective and anxiety disorders, compared with healthy adults, between 1998 and 2003. Method:, Secondary analyses of multi-stage probability samples of community residents (n1998 = 37 580 and n2003 = 36 088) obtained from repeat administrations of an Australian population survey. Results:, Proportionally, fewer people with affective or anxiety disorders were employed compared with well controls. Extent of employment restrictions, sex, age left school, country of birth, age and educational attainment were strong correlates of labour force participation and current employment. These effects were stable despite improved labour market conditions in 2003. Conclusion:, These results can inform decisions about access to substantial forms of employment assistance. Subgroups of people with anxiety and depression, with severe employment restrictions, low education, low language proficiency, aged 15,24 years, or aged 55 years or more, may require greater access to substantial employment assistance. [source] Measuring kinaesthetic sensitivity in typically developing childrenDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2009KRISTEN PICKETT MS This study presents a method to quantify a child's sensitivity to passive limb motion, which is an important aspect of kinaesthesia not easily examined clinically. Psychophysical detection thresholds to passive forearm motion were determined in a group of 20 typically developing pre-adolescent children (mean age 12y 6mo, SD 10mo, range 11,13y) and a group of 10 healthy adults (mean age 29y 10mo, SD 10y 7mo, range 18,50y). A newly designed passive motion apparatus was used to measure the time to detection of forearm motion and the errors in determining movement direction. Results showed that limb motion sensitivity became increasingly variable below 0.3°/s in children and adults. In comparison with adults, movement detection times in the pediatric group were increased by between 4% and 108% for the range of tested velocities (0.075,1.35°/s). At 0.075°/s, 5% of the children, but 50% of the adults, made no directional error, indicating that motion perception became unreliable at such low velocity in both groups. The findings demonstrate that sensitivity to passive forearm motion in children should be tested at a range between 0.075 and 0.3°/s. They further suggest that passive motion sensitivity may not be fully developed in pre-adolescent children. [source] Does aerobic fitness influence microvascular function in healthy adults at risk of developing Type 2 diabetes?DIABETIC MEDICINE, Issue 4 2005A. R. Middlebrooke Abstract Aim To investigate whether aerobic fitness is associated with skin microvascular function in healthy adults with an increased risk of developing Type 2 diabetes. Methods Twenty-seven healthy normal glucose-tolerant humans with either a previous diagnosis of gestational diabetes or having two parents with Type 2 diabetes and 27 healthy adults who had no history of diabetes were recruited. Maximal oxygen uptake was assessed using an incremental exercise test to exhaustion. Skin microvascular function was assessed using laser Doppler techniques as the maximum skin hyperaemic response to a thermal stimulus (maximum hyperaemia) and the forearm skin blood flow response to the iontophoretic application of acetylcholine (ACh) and sodium nitroprusside. Results Maximal oxygen uptake was not significantly different in the ,at-risk' group compared with healthy controls. Maximum hyperaemia was reduced in those ,at risk' (1.29 ± 0.30 vs. 1.46 ± 0.33 V, P = 0.047); however, the peak response to acetylcholine or sodium nitroprusside did not differ in the two groups. A significant positive correlation was demonstrated between maximal oxygen uptake and maximum hyperaemia (r = 0.52, P = 0.006 l/min and r = 0.60, P = 0.001 ml/kg/min) and peak ACh response (r = 0.40, P = 0.04 l/min and r = 0.47, P = 0.013 ml/kg/min) in the ,at-risk' group when expressed in absolute (l/min) or body mass-related (ml/kg/min) terms. No significant correlations were found in the control group. Conclusions In this ,at-risk' group with skin microvascular dysfunction maximal oxygen uptake was not reduced compared with healthy controls. However, in the ,at-risk' group alone, individuals with higher levels of aerobic fitness also had better microvascular and endothelial responsiveness. [source] EXAMINATION OF RESPIRATORY AND CIRCULATORY DYNAMICS DURING EXAMINATION USING A THIN GASTROINTESTINAL ENDOSCOPE IN ADVANCED-AGE SUBJECTSDIGESTIVE ENDOSCOPY, Issue 2 2007Miyako Niki Background:, Endoscopic examination influences cardiovascular hemodynamics. Upper gastrointestinal examinations are currently performed with a thin endoscope. In the present study, respiratory and circulatory dynamics and autonomic nervous activity using a thin endoscope (XP260) or a standard endoscope (XQ240) were investigated. Methods:, The subjects were 25 healthy adults aged less than 60 years (middle-aged group) and 15 healthy adults aged 60 years or older (advanced-age group). Percutaneous oxygen saturation, tonometric blood pressure, heart rate, and autonomic nervous activity were evaluated before the examination. After the endoscopic procedure, a questionnaire survey regarding examination-related stress was conducted. Results:, In the questionnaire survey, the proportion of subjects who answered ,very stress free' in the thin endoscope group was significantly higher than that in the standard endoscope group. The low frequency power of blood pressure variability (LFBP), an indicator of sympathetic nervous activity, was significantly lower during the thin endoscopic procedure than during the standard endoscopic procedure. Moreover, the ratio of low frequency power to high frequency power of heart rate variability (LFRR/HFRR), an indicator of sympathetic nervous activity, was significantly lower during thin endoscopic procedure than during the standard endoscopic procedure. The maximum rates of change in the LFBP and HFRR powers in the advanced-age group using thin and standard endoscopic procedures were significantly lower than in the middle-aged group. Conclusions:, The findings, although not in cross-over study, suggest that a thin endoscope has a less marked influence on circulatory kinetics. Gastrointestinal endoscopic examinations using a thin endoscope might reduce complications related to endoscopic screening examinations in advanced-age subjects. [source] A comparison of five fMRI protocols for mapping speech comprehension systemsEPILEPSIA, Issue 12 2008Jeffrey R. Binder Summary Aims:, Many fMRI protocols for localizing speech comprehension have been described, but there has been little quantitative comparison of these methods. We compared five such protocols in terms of areas activated, extent of activation, and lateralization. Methods:, fMRI BOLD signals were measured in 26 healthy adults during passive listening and active tasks using words and tones. Contrasts were designed to identify speech perception and semantic processing systems. Activation extent and lateralization were quantified by counting activated voxels in each hemisphere for each participant. Results:, Passive listening to words produced bilateral superior temporal activation. After controlling for prelinguistic auditory processing, only a small area in the left superior temporal sulcus responded selectively to speech. Active tasks engaged an extensive, bilateral attention, and executive processing network. Optimal results (consistent activation and strongly lateralized pattern) were obtained by contrasting an active semantic decision task with a tone decision task. There was striking similarity between the network of brain regions activated by the semantic task and the network of brain regions that showed task-induced deactivation, suggesting that semantic processing occurs during the resting state. Conclusions:, fMRI protocols for mapping speech comprehension systems differ dramatically in pattern, extent, and lateralization of activation. Brain regions involved in semantic processing were identified only when an active, nonlinguistic task was used as a baseline, supporting the notion that semantic processing occurs whenever attentional resources are not controlled. Identification of these lexical-semantic regions is particularly important for predicting language outcome in patients undergoing temporal lobe surgery. [source] Gabapentin Increases Slow-wave Sleep in Normal AdultsEPILEPSIA, Issue 12 2002Nancy Foldvary-Schaefer Summary: ,Purpose: The older antiepileptic drugs (AEDs) have a variety of effects on sleep, including marked reduction in rapid-eye-movement (REM) sleep, slow-wave sleep (SWS), and sleep latency, and an increase in light sleep. The effects of the newer AEDs on sleep are unknown. Our purpose was to study the effect of gabapentin (GBP) on sleep. Methods: Ten healthy adults and nine controls were the subjects of this study. All underwent baseline and follow-up polysomnography (PSG) and completed sleep questionnaires. After baseline, the treated group received GBP titrated to 1,800 mg daily. Polygraphic variables and Epworth Sleepiness Scale (ESS) scores, a subjective measure of sleep propensity, were compared by using the Wilcoxon signed rank test. Results: Nine of the treated subjects achieved the target dose; one was studied with 1,500 mg daily because of dizziness experienced at the higher dose. GBP-treated subjects had an increase in SWS compared with baseline. No difference in the ESS or other polygraphic variables was observed. However, a minor reduction in arousals, awakenings, and stage shifts was observed in treated subjects. Conclusions: GBP appears to be less disruptive to sleep than are some of the older AEDs. These findings may underlie the drug's therapeutic effect in the treatment of disorders associated with sleep disruption. [source] Covariance-based subdivision of the human striatum using T1-weighted MRIEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2008Michael X Cohen Abstract The striatum plays a key role in many cognitive and emotional processes, and displays an intricate pattern of connectivity with cortical and subcortical structures. Invasive tracing work in rats and non-human primates demonstrates that the striatum can be segregated into subregions based on similar clustering of input and output fibers. In contrast, the human striatum is typically segregated according to local anatomical landmarks without considering natural boundaries formed by functional/anatomical networks. Here, we used non-invasive magnetic resonance (MR) imaging in young, healthy adults to define subregions of the human striatum based on volume correlations with other subcortical and cortical structures. We present three methods to delineate anatomical volumetric correlations based on gray matter content estimated from T1-weighted MR images. We observed both consistencies with and divergences from invasive tracing work in animals, suggesting that magnetic resonance imaging (MRI)-based covariance likely does not correspond to direct anatomical connections, although it might index other forms of connectivity or tissue type similarity. These novel approaches may be useful in understanding connectivity of other regions, and changes in connectivity in patient or ageing populations. [source] Influence of drinking method on tooth-surface pH in relation to dental erosionEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 6 2004Ann-Katrin Johansson The aim of this investigation was to study the intraoral pH response on tooth surfaces in relation to dental erosion during and after drinking a sugar-free cola-type soft drink. Six different methods of drinking were tested in a randomized order: holding; short-sipping; long-sipping; gulping; nipping; and sucking. Two methods of pH measurement were used in two series of individuals. In the first series, pH was measured by using the microtouch method in 12 healthy adults at three dental erosion-prone sites: 11 palatally; 11 buccally; and at the mesiobuccal cusp tip of 16. In the second series, pH was measured by using the telemetric method in 6 healthy individuals, producing continuous recordings of pH by means of a glass electrode in a specified approximal area. The two series showed similar results, although the telemetric method generally recorded larger pH falls. Holding the drink in the mouth before swallowing led to the most pronounced pH drop, followed by the long-sipping method. Gulping resulted in only a small decrease of pH. No differences among the three intraoral sites were found when analyzed by using the microtouch method. The conclusion from this study is that the drinking method strongly affects tooth-surface pH and thereby the risk for dental erosion. It therefore seems appropriate to include advice on the method of drinking in dietary counseling related to dental erosion. [source] PCR DGGE and RT-PCR DGGE show diversity and short-term temporal stability in the Clostridium coccoides,Eubacterium rectale group in the human intestinal microbiotaFEMS MICROBIOLOGY ECOLOGY, Issue 3 2006Johanna Maukonen Abstract As the Clostridium coccoides,Eubacterium rectale (Erec; clostridial phylogenetic cluster XIVa) group is one of the major groups of the human intestinal microbiota, DNA- and RNA-based population analysis techniques (denaturing gradient gel electrophoresis; DGGE) were developed and applied to assess the diversity and temporal stability (6 months,2 years) of this faecal clostridial microbiota in 12 healthy adults. The stability of the Erec group was compared with the stability of the predominant bacterial microbiota, which was also assessed with PCR-DGGE. In addition, the Erec group was quantified with a hybridization-based method. According to our results, the Erec group was diverse in each subject, but interindividual uniqueness was not as clear as that of the predominant bacteria. The Erec group was found to be temporally as stable as the predominant bacteria. Over 200 clones obtained from two samples proved the developed method to be specific. However, the amount of bacteria belonging to the Erec group was not related to the diversity of that same bacterial group. In conclusion, the newly developed DGGE method proved to be a valuable and specific tool for the direct assessment of the stability of the Erec group, demonstrating diversity in addition to short-term stability in most of the subjects studied. [source] Impact of inter-individual differences in drug metabolism and pharmacokinetics on safety evaluationFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004J.L.C.M. Dorne Abstract Safety evaluation aims to assess the dose,response relationship to determine a dose/level of exposure for food contaminants below which no deleterious effect is measurable that is ,without appreciable health risk' when consumed daily over a lifetime. These safe levels, such as the acceptable daily intake (ADI) have been derived from animal studies using surrogates for the threshold such as the no-observed-adverse-effect-level (NOAEL). The extrapolation from the NOAEL to the human safe intake uses a 100-fold uncertainty factor, defined as the product of two 10-fold factors allowing for human variability and interspecies differences. The 10-fold factor for human variability has been further subdivided into two factors of 100.5 (3.16) to cover toxicokinetics and toxicodynamics and this subdivsion allows for the replacement of an uncertainty factor with a chemical-specific adjustment factor (CSAF) when compound-specific data are available. Recently, an analysis of human variability in pharmacokinetics for phase I metabolism (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, hydrolysis, alcohol dehydrogenase), phase II metabolism (N-acetyltransferase, glucuronidation, glycine conjugation, sulphation) and renal excretion was used to derive pathway-related uncertainty factors in subgroups of the human population (healthy adults, effects of ethnicity and age). Overall, the pathway-related uncertainty factors (99th centile) were above the toxicokinetic uncertainty factor for healthy adults exposed to xenobiotics handled by polymorphic metabolic pathways (and assuming the parent compound was the proximate toxicant) such as CYP2D6 poor metabolizers (26), CYP2C19 poor metabolizers (52) and NAT-2 slow acetylators (5.2). Neonates were the most susceptible subgroup of the population for pathways with available data [CYP1A2 and glucuronidation (12), CYP3A4 (14), glycine conjugation (28)]. Data for polymorphic pathways were not available in neonates but uncertainty factors of up to 45 and 9 would allow for the variability observed in children for CYP2D6 and CYP2C19 metabolism, respectively. This review presents an overview on the history of uncertainty factors, the main conclusions drawn from the analysis of inter-individual differences in metabolism and pharmacokinetics, the development of pathway-related uncertainty factors and their use in chemical risk assessment. [source] Investigation of 17 candidate genes for personality traits confirms effects of the HTR2A gene on novelty seekingGENES, BRAIN AND BEHAVIOR, Issue 4 2009A. Heck Genes involved in serotonergic and dopaminergic neurotransmission have been hypothesized to affect different aspects of personality, but findings from genetic association studies did not provide conclusive results so far. In previous studies, however, only one or a few polymorphisms within single genes were investigated neglecting the possibility that the genetic associations might be more complex comprising several genes or gene regions. To overcome this limitation, we performed an extended genetic association study analyzing 17 serotonergic (SLC6A4, HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR6, MAOA, TPH1, TPH2) and dopaminergic genes (SLC6A3, DRD2, DRD3, DRD4, COMT, MAOA, TH, DBH), which have been previously reported to be implicated with personality traits. One hundred and ninety-five single nucleotide polymorphisms (SNPs) within these genes were genotyped with the Illumina BeadChip technology (HumanHap300, Human-1) in a sample of 366 mentally healthy Caucasians. Additionally, we tried to replicate our results in an independent sample of further 335 Caucasians. Personality traits in both samples were assessed with the German version of Cloninger's Tridimensional Personality Questionnaire. From 30 SNPs showing associations at a nominal level of significance, two intronic SNPs, rs2770296 and rs927544, both located in the HTR2A gene, withstood correction for multiple testing. These SNPs were associated with the personality trait novelty seeking. The effect of rs927544 could be replicated for the novelty seeking subscale extravagance, and the same SNP was also associated with extravagance inthe combined samples. Our results show that HTR2A polymorphisms modulate facets of novelty seeking behaviour in healthy adults suggesting that serotonergic neurotransmission is involved in this phenotype. [source] Tryptophan hydroxylase 1 gene haplotypes modify the effect of a hostile childhood environment on adulthood harm avoidanceGENES, BRAIN AND BEHAVIOR, Issue 4 2007L. Keltikangas-Järvinen We conducted a series of tests to determine whether there is any association between tryptophan hydroxylase 1 (TPH1) and temperament in adulthood. In addition to testing for main effects, we investigated whether TPH1 gene variation modifies the influence of childhood environment on temperament in adulthood. The subjects were 341 healthy adults whose childhood environment was assessed by their mothers in 1980 and who self-rated their temperaments twice, in 1997 and 2001. We found no association between the TPH1 gene and temperament; however, among women, the TPH1 gene modified a relationship between adverse childhood environment and harm avoidance in adulthood. This finding was confirmed in the same sample in another test setting 4 years later. The presence of the A/A haplotype of the TPH1 intron 7 A218A and A779C polymorphism predicted a high level of adulthood harm avoidance in the presence of a hostile childhood environment as defined in terms of emotional rejection, maternal neglect and harsh and inconsistent discipline. In addition, the findings suggest a gene,environment correlation for novelty seeking in men. [source] Comparison of a Stool Antigen Test and Serology for the Diagnosis of Helicobacter pylori Infection in Mass SurveyHELICOBACTER, Issue 2 2009Tadashi Shimoyama Abstract Background: Serum antibody to Helicobacter pylori is tested in mass screening for gastric cancer along with the level of serum pepsinogens (PG) I and II. Recently, stool antigen tests have been developed as a new non-invasive test. We examined H. pylori infection by both serology and stool antigen test in a mass survey and compared the results to estimate applicability of stool antigen test for mass survey. Methods: A total of 994 healthy adults who received mass survey in April 2005 were tested. There were 379 men and 615 women, and the mean age was 57.7 years old. Stool samples were used to measure a H. pylori- specific antigen by enzyme immunoassay. Serum samples were tested for the prevalence of IgG antibody to H. pylori, and the level of PGs I and II was also measured to determine the presence of atrophic gastritis. Results: Infection of H. pylori was defined as positive 61.4% and 56.4% by serology and stool antigen test, respectively. The concordance of both tests was not affected by gender and age of the subjects but difference was seen in subjects with atrophic gastritis. In particular, positivity of stool antigen test (81.8%) was significantly lower than that of serology (88.7%, p < .05) in 303 subjects with severe atrophic gastritis. Conclusions: Stool antigen test, which detects present but not previous infection of H. pylori, would be applicable to diagnose H. pylori infection in mass survey. Usefulness of stool antigen tests for the screening of gastric cancer should be examined. [source] Pharmacology and safety of glycerol phenylbutyrate in healthy adults and adults with cirrhosis,,HEPATOLOGY, Issue 6 2010Brendan M. McGuire Phenylbutyric acid (PBA), which is approved for treatment of urea cycle disorders (UCDs) as sodium phenylbutyrate (NaPBA), mediates waste nitrogen excretion via combination of PBA-derived phenylacetic acid with glutamine to form phenylactylglutamine (PAGN) that is excreted in urine. Glycerol phenylbutyrate (GPB), a liquid triglyceride pro-drug of PBA, containing no sodium and having favorable palatability, is being studied for treatment of hepatic encephalopathy (HE). In vitro and clinical studies have been performed to assess GPB digestion, safety, and pharmacology in healthy adults and individuals with cirrhosis. GPB hydrolysis was measured in vitro by way of pH titration. Twenty-four healthy adults underwent single-dose administration of GPB and NaPBA and eight healthy adults and 24 cirrhotic subjects underwent single-day and multiple-day dosing of GPB, with metabolites measured in blood and urine. Simulations were performed to assess GPB dosing at higher levels. GPB was hydrolyzed by human pancreatic triglyceride lipase, pancreatic lipase-related protein 2, and carboxyl-ester lipase. Clinical safety was satisfactory. Compared with NaPBA, peak metabolite blood levels with GPB occurred later and were lower; urinary PAGN excretion was similar but took longer. Steady state was achieved within 4 days for both NaPBA and GPB; intact GPB was not detected in blood or urine. Cirrhotic subjects converted GPB to PAGN similarly to healthy adults. Simulations suggest that GPB can be administered safely to cirrhotic subjects at levels equivalent to the highest approved NaPBA dose for UCDs. Conclusion: GPB exhibits delayed release characteristics, presumably reflecting gradual PBA release by pancreatic lipases, and is well tolerated in adults with cirrhosis, suggesting that further clinical testing for HE is warranted. (HEPATOLOGY 2010;) [source] The neural control of bimanual movements in the elderly: Brain regions exhibiting age-related increases in activity, frequency-induced neural modulation, and task-specific compensatory recruitmentHUMAN BRAIN MAPPING, Issue 8 2010Daniel J. Goble Abstract Coordinated hand use is an essential component of many activities of daily living. Although previous studies have demonstrated age-related behavioral deficits in bimanual tasks, studies that assessed the neural basis underlying such declines in function do not exist. In this fMRI study, 16 old and 16 young healthy adults performed bimanual movements varying in coordination complexity (i.e., in-phase, antiphase) and movement frequency (i.e., 45, 60, 75, 90% of critical antiphase speed) demands. Difficulty was normalized on an individual subject basis leading to group performances (measured by phase accuracy/stability) that were matched for young and old subjects. Despite lower overall movement frequency, the old group "overactivated" brain areas compared with the young adults. These regions included the supplementary motor area, higher order feedback processing areas, and regions typically ascribed to cognitive functions (e.g., inferior parietal cortex/dorsolateral prefrontal cortex). Further, age-related increases in activity in the supplementary motor area and left secondary somatosensory cortex showed positive correlations with coordinative ability in the more complex antiphase task, suggesting a compensation mechanism. Lastly, for both old and young subjects, similar modulation of neural activity was seen with increased movement frequency. Overall, these findings demonstrate for the first time that bimanual movements require greater neural resources for old adults in order to match the level of performance seen in younger subjects. Nevertheless, this increase in neural activity does not preclude frequency-induced neural modulations as a function of increased task demand in the elderly. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc. [source] The effects of the glutamate antagonist memantine on brain activation to an auditory perception taskHUMAN BRAIN MAPPING, Issue 11 2009Heidi van Wageningen Abstract Glutamate is critically involved in the regulation of cognitive functions in humans. There is, however, sparse evidence regarding how blocking glutamate action at the receptor site during a cognitive task affects brain activation. In the current study, the effects of the glutamate antagonist memantine were examined with functional magnetic resonance imaging (fMRI). Thirty-one healthy adults were scanned twice in a counter-balanced design, either in a no-drug session or after administration of memantine for 21 days. The subjects performed a simple auditory perception task with consonant-vowel stimuli. Group-level spatial independent component analysis (ICA) was used to decompose the data and to extract task-related activations. The focus was on four task-related ICA components with frontotemporal localization. The results showed that glutamate-blockage resulted in a significant enhancement in one component, with no significant effect in the other three components. The enhanced effect of memantine was in the middle temporal gyrus, superior frontal gyrus, and middle frontal gyrus. It is suggested that the results reflect effects of glutamatergic processes primarily through non- N -methyl- D -aspartate (NMDA) receptor pathways. Moreover, the results demonstrate that memantine can be used as a probe which allows for studying the effect of excitatory neurotransmission on neuronal activation. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] Frontolimbic responses to emotional face memory: The neural correlates of first impressionsHUMAN BRAIN MAPPING, Issue 11 2009Theodore D. Satterthwaite Abstract First impressions, especially of emotional faces, may critically impact later evaluation of social interactions. Activity in limbic regions, including the amygdala and ventral striatum, has previously been shown to correlate with identification of emotional content in faces; however, little work has been done describing how these signals may influence emotional face memory. We report an event-related functional magnetic resonance imaging study in 21 healthy adults where subjects attempted to recognize a neutral face that was previously viewed with a threatening (angry or fearful) or nonthreatening (happy or sad) affect. In a hypothesis-driven region of interest analysis, we found that neutral faces previously presented with a threatening affect recruited the left amygdala. In contrast, faces previously presented with a nonthreatening affect activated the left ventral striatum. A whole-brain analysis revealed increased response in the right orbitofrontal cortex to faces previously seen with threatening affect. These effects of prior emotion were independent of task performance, with differences being seen in the amygdala and ventral striatum even if only incorrect trials were considered. The results indicate that a network of frontolimbic regions may provide emotional bias signals during facial recognition. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] Accessing newly learned names and meanings in the native languageHUMAN BRAIN MAPPING, Issue 3 2009Annika Hultén Abstract Ten healthy adults encountered pictures of unfamiliar archaic tools and successfully learned either their name, verbal definition of their usage, or both. Neural representation of the newly acquired information was probed with magnetoencephalography in an overt picture-naming task before and after learning, and in two categorization tasks after learning. Within 400 ms, activation proceeded from occipital through parietal to left temporal cortex, inferior frontal cortex (naming) and right temporal cortex (categorization). Comparison of naming of newly learned versus familiar pictures indicated that acquisition and maintenance of word forms are supported by the same neural network. Explicit access to newly learned phonology when such information was known strongly enhanced left temporal activation. By contrast, access to newly learned semantics had no comparable, direct neural effects. Both the behavioral learning pattern and neurophysiological results point to fundamentally different implementation of and access to phonological versus semantic features in processing pictured objects. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [source] Functional magnetic resonance imaging response to increased verbal working memory demands among patients with multiple sclerosisHUMAN BRAIN MAPPING, Issue 1 2006Lawrence H. Sweet Abstract Multiple sclerosis (MS) patients frequently experience impaired verbal working memory (VWM). Functional magnetic resonance imaging (fMRI) may help identify neural mechanisms underlying these deficits. Neuroimaging studies of healthy adults have characterized responses associated with increased VWM demands during the n-Back task, suggesting that this experimental paradigm could help identify neural correlates of VWM deficits among MS patients. Fifteen MS patients and 15 matched control participants completed the n-Back during whole-brain fMRI. Mean signal during adjacent 0-Back blocks was subtracted, on a voxel-wise basis, from mean signal observed during n-Back blocks. Resulting difference scores for 1-, 2-, and 3-Back were compared across groups and difficulty levels. Signal intensity was positively related to difficulty level in anterior regions, including premotor, supplementary motor, and dorsolateral prefrontal cortices. MS patients exhibited significantly greater intensity in these areas compared to controls during the 1-Back, while portions of the left superior frontal gyrus, cingulate, and parahippocampal gyri were relatively less intense at more difficult levels. MS group responses were slower during the 1-Back and tended to be slower during the 3-Back; however, accuracy did not differ at any level. Lesion load was positively related to only 1-Back activity and unrelated to any performance measure. Results suggest that compensatory activity occurs among MS patients matched on performance accuracy. Furthermore, compensatory activity occurs predominantly in regions associated with VWM, and this may decline relative to controls as task demands increase. These findings may help to explain why MS patient performance decreases as a function of effort on neuropsychological tests. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc. [source] Acute cognitive effects of donepezil in young, healthy volunteersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2009Ana LC Zaninotto Abstract Objective The acute nootropic potential of donepezil in young healthy volunteers has not been adequately investigated mainly because in previous studies: (1) effects were assessed before peak-plasma concentration (Tmax) was reached; (2) only a few cognitive processes were assessed. Here we investigated a myriad of cognitive effects of augmentation of acetylcholine using an acute dose of donepezil in healthy adults at theoretical Tmax. Methods This was a double-blind, placebo controlled, parallel group design study of cognitive effects of acute oral donepezil (5,mg). Subjects were tested twice after donepezil ingestion: 90,min (time that coincides with previous testing in the literature) and 210,min. (theoretical Tmax). The test battery included tasks that tap cognitive domains that are sensitive to acetylcholine manipulations. Results At both testing times donepezil improved long-term recall of prose, objects recall, recall of spatial locations, and integration of objects with their locations, some effects having been related to self-reported mood enhancement. However, improvement of performance in the central executive measure (backward digit span) occurred only at Tmax. Conclusion Positive cognitive effects of acute donepezil can be observed in various cognitive domains including mood, but its full nootropic potential is more clearly found close to theoretical peak-plasma concentration. Copyright © 2009 John Wiley & Sons, Ltd. [source] Acute cholecystokinin effects on event-related potentials in healthy volunteersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2002Verner J. Knott Abstract This study investigated the effects of a continuous slow infusion of cholecystokinin tetrapeptide (CCK-4), a neuropeptide with panicogenic properties, on brain event-related potentials (ERPs) in healthy adults. Twenty-four volunteers, 15 females and 9 males, were assigned to infusion with either placebo or CCK-4 in a randomized, double-blind, parallel group design. ERPs, elicited within a standard auditory odd-ball paradigm requiring the counting of rare (20%) occurring ,deviant' tones interspersed among more frequent (80%) occurring ,standard' tones, were assessed once before infusion, and at 10,min and 40,min after the onset of infusion. Compared with the placebo, CCK-4 delayed the latencies of N100 and P200 components elicited by ,deviant' stimuli. No significant treatment differences were observed with respect to N200, P300b, mood or adverse symptoms. These preliminary findings suggest that CCK-4 may interfere with information processing relating to the selection of significant stimuli and as such, may be of relevance to mechanisms underlying panic disorder. Copyright © 2002 John Wiley & Sons, Ltd. [source] Report on the vitamin D status of adult and pediatric patients with inflammatory bowel disease and its significance for bone health and diseaseINFLAMMATORY BOWEL DISEASES, Issue 12 2006Helen M. Pappa MD Abstract Vitamin D is a hormone responsible for calcium homeostasis and essential for bone mineralization throughout the lifespan. Recent studies revealed a high prevalence of hypovitaminosis D among healthy adults and children, especially in the northern hemisphere, and a link between this condition and suboptimal bone health. Moreover, maintenance of what are today considered optimal vitamin D stores has not been achieved throughout the year with currently recommended daily intake for vitamin D. The prevalence of hypovitaminosis D is even higher among adults with inflammatory bowel disease (IBD), a situation that may be caused by malabsorption and gastrointestinal losses through an inflamed intestine, among other factors. In children with IBD, existing reports of vitamin D status are scarce. The relationship between vitamin D status and bone health, although well-established in healthy adults and children, has been controversial among adults and children with IBD, and the reasons for this have not been investigated to date. Studies in animal models of colitis and in vitro human studies support a role of vitamin D in the regulation of the immune system of the gut and the potential of vitamin D and its derivatives as therapeutic adjuncts in the treatment of IBD. This role of vitamin D has not been investigated with translational studies to date. Currently, there are no guidelines for monitoring vitamin D status, treating hypovitaminosis D, and maintaining optimal vitamin D stores in patients with IBD. These tasks may prove particularly difficult because of malabsorption and gastrointestinal losses that are associated with IBD. [source] | |||||||||||||||||||||||||||||||||||||