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Selected AbstractsHuman 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] Postprandial hyperglycaemia in type 2 diabetes: pathophysiological aspects, teleological notions and flags for clinical practiceDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S2 2004Eleni I. Boutati Abstract Type 2 diabetes subjects carry an excess risk for micro- and macrovascular disease and a higher cardiovascular morbidity and mortality rate. The beneficial impact of tight glycaemic control,evidenced by the integrated marker of fasting glucose and postprandial glucose values, the HbA1c,for the prevention of microvascular complications is definitely confirmed. Over the past few years, several studies have identified postprandial hyperglycaemia as a better predictor of cardiovascular or even of all-cause mortality, as well as an independent risk factor for atherosclerosis. The continuous glucose monitoring could offer a rationale means for the detection of postprandial hyperglycaemia and ultimately for its effective management. Advances in technology keep a promise for a reliable, convenient and closer to the idea of the artificial endocrine pancreas glucose sensor. Subcutaneous glucose levels charted by one of the new sensors were found to be well correlated with venous glucose measurements. Intervention for a healthy lifestyle is frequently hampered by patients' poor compliance. The availability of diverse antidiabetic agents provides options for targeting the glycaemic goal and a choice more fitted to the particularized pathophysiology of each individual subject. Drugs targeting postprandial glycaemia may prove to represent the ,sine qua non' for the ,return' of postprandial glucose values at a ,non-deleterious' threshold, either as monotherapy for the early stages of the disease or as combination therapy later in the progression of diabetes. Copyright © 2004 John Wiley & Sons, Ltd. [source] Simplified intersubject averaging on the cortical surface using SUMAHUMAN BRAIN MAPPING, Issue 1 2006Brenna D. Argall Abstract Task and group comparisons in functional magnetic resonance imaging (fMRI) studies are often accomplished through the creation of intersubject average activation maps. Compared with traditional volume-based intersubject averages, averages made using computational models of the cortical surface have the potential to increase statistical power because they reduce intersubject variability in cortical folding patterns. We describe a two-step method for creating intersubject surface averages. In the first step cortical surface models are created for each subject and the locations of the anterior and posterior commissures (AC and PC) are aligned. In the second step each surface is standardized to contain the same number of nodes with identical indexing. An anatomical average from 28 subjects created using the AC,PC technique showed greater sulcal and gyral definition than the corresponding volume-based average. When applied to an fMRI dataset, the AC,PC method produced greater maximum, median, and mean t -statistics in the average activation map than did the volume average and gave a better approximation to the theoretical-ideal average calculated from individual subjects. The AC,PC method produced average activation maps equivalent to those produced with surface-averaging methods that use high-dimensional morphing. In comparison with morphing methods, the AC,PC technique does not require selection of a template brain and does not introduce deformations of sulcal and gyral patterns, allowing for group analysis within the original folded topology of each individual subject. The tools for performing AC,PC surface averaging are implemented and freely available in the SUMA software package. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc. [source] Evaluation of the relationship between smoking during pregnancy and subgingival microbiotaJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 1 2005Nurcan Buduneli Abstract Background: Numerous studies have shown that smoking negatively affects periodontal health. Hormonal changes, which occur during pregnancy have also been reported to have adverse effects on the periodontal tissues or indirectly through alterations in the subgingival bacterial flora. At present, no knowledge exists concerning possible effects of smoking on the composition of subgingival plaque in pregnancy. The purpose of the present study was to evaluate the effects of smoking during pregnancy on the subgingival plaque bacteria most commonly associated with periodontal disease. Methods: A total number of 181 women were examined within 72 h post-partum. Smoking status was recorded by means of a self-reported questionnaire and the study population was divided into three groups; non-smokers, light smokers, and heavy smokers. In each woman, two subgingival plaque samples were obtained from mesio- or disto-buccal aspect of randomly selected one molar and one incisor tooth by sterile paperpoints. Clinical periodontal recordings comprising presence of dental plaque, bleeding on probing (BOP), and probing pocket depth (PPD) were performed at six sites per each tooth at all teeth. Plaque samples were analysed by checkerboard DNA,DNA hybridization with respect to 12 bacterial species. In all analyses, the individual subject was the computational unit. Thus, mean values for all clinical parameters were calculated and bacterial scores from each individual sample were averaged. Statistical methods included ,2 test, Kruskal,Wallis test and Mann,Whitney U -test. Results: Mean ages were similar in the study groups. Plaque, BOP and PPD recordings were lower in the heavy-smoker group, but the differences were not statistically significant (p>0.05). The detection rates and bacterial loads of the specific subgingival bacteria exhibited no significant differences between the groups. No correlation could be found between smoking status and detection rates and bacterial loads of various bacterial species. Conclusion: The present findings suggest that smoking during pregnancy does not have a significant effect on the composition of subgingival plaque bacteria. [source] Dose-response relationship of rocuronium: A comparison of electromyographic vs. acceleromyographic-derived valuesACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2005A. F. Kopman Background: Acceleromyography (AMG) is being employed with increasing frequency as a research tool. However, there is almost no information available regarding the accuracy of values for drug potency obtained using AMG. This study was an attempt to determine if AMG-derived ED50/95 values are interchangeable with those measured with a more traditional neuromuscular monitor. Methods: Thirty adult patients were studied. Anesthesia was induced and maintained with N20, propofol, and supplementation opioid. Tracheal intubation was accomplished without muscle relaxants. Simultaneous ipsilateral AMG and EMG responses to 0.10 Hz stimulation was recorded. Following instrument calibrations, a single dose of rocuronium was administered. The first patient received a bolus of 0.17 mg kg,1 of rocuronium. Using the Hill equation with a postulated slope of 4.50, the ED50 was calculated. The second subject received a dose which approximated the calculated ED50 for patient no. 1. Successive subjects were given a dose based on the running average of the estimated ED50. Results: The AMG-derived ED50/95 values for rocuronium (0.163 ± 0.055 and 0.314 ± 0.105 mg mg,1) were virtually identical to those established using EMG (0.159 ± 0.043 and 0.306 ± 0.084 mg kg,1). While mean peak twitch depression (,T1) was the same in both groups for individual subjects ,T1 differed by ± 20% (95% confidence interval). Discussion: Acceleromyography-derived twitch heights for individual patients are not necessarily interchangeable with information obtained using electromyography. Nevertheless, acceleromyography appears to be a valid methodology for determining the drug potency when a population rather than an individual subject is being studied. [source] Circadian Variation in QT Dispersion Determined from a 12-Lead Holter Recording: A Methodological Study of an Age- and Sex-Stratified Group of Healthy SubjectsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2007Stig Hansen M.D. Background: QT dispersion is considered to reflect inhomogeneity of myocardial repolarization. Method: The circadian variation of QT interval dispersion was examined in 95 healthy subjects using 24-hour Holter monitoring. Three different methods of lead selection were applied: all 12 leads (QTdisp 12), only precordial leads (QTdisp 6), and the pair of leads selected at 3 a.m. in which the longest and shortest QT intervals were found in each individual subject (QTdisp 2). Results: A preliminary methodological study including measurements from every minute in 10 subjects revealed no significant circadian variation using mean values of QTdisp 12, QTdisp 6, or QTdisp 2 obtained every hour, every 2, or every 4 hours, except in QTdisp 6, which demonstrated a significant circadian variation (P < 0.01) in 1-hour measurements. Analysis of all 95 subjects using measurements obtained every 4 hours revealed a significant circadian variation in QTdisp 12 and QTdisp 6 (P < 0.0001), whereas no circadian variation was seen in QTdisp 2. A subdivision into 10-year age groups revealed that subjects at age >50 years had a significant circadian variation in QTdisp 12 and QTdisp 6, but not in QTdisp 2. Only in males a significant circadian variation was seen in QTdisp 12 (P < 0.0001), whereas QTdisp 6 demonstrated a circadian variation both in females (P < 0.001) and in males (P < 0.0001). Conclusions: Selection of leads is of crucial importance for repetitive measurements of QT dispersion. Circadian variation was detected in subjects over 50 years of age, when all 12 or only the 6 precordial leads were taken into account. [source] Diabetes control and complications: the role of glycated haemoglobin, 25 years onDIABETIC MEDICINE, Issue 7 2004S. L. Jeffcoate Abstract The long-term complications of diabetes have major consequences for individual subjects and growing healthcare delivery and cost implications for society. Evidence for the benefits of good glycaemic control, as monitored by glycated haemoglobin measurements, has been developed in the 25 years since they were introduced to the point where HbA1c assays play central roles in patient management, clinical guidance and audit, and clinical trial design. In this review this evidence is examined and three classes of uncertainty identified that diminish confidence in the effectiveness of these roles for HbA1c. 1Analytical variability between different methods for HbA1c has restricted the application of clinical targets and this problem has recently been addressed by reference method standardization. There are two approaches to this which result in different HbA1c values and this discrepancy needs to be resolved. 2Biological variability in HbA1c values between individuals also restricts its predictive role when applied to populations. The correlations between HbA1c measurements and various components of glycaemia (overall, fasting, postprandial) are still uncertain and differences in protein glycation and de-glycation are greater between subjects than often thought. The influence of variability in erythrocyte life span is an area where research is needed, especially in diabetic subjects. 3Clinical variability is the most important and complex area of uncertainty. A predictive link between HbA1c and clinical outcomes is not as clear-cut as often stated. The correlation with the development of microvascular disease is well established in Type 1 diabetes, but in Type 2 subjects (90% of those with diabetes) the evidence that HbA1c monitoring is of value in predicting or preventing macrovascular disease is not strong, although it is the major cause of morbidity and early death in this group. It is recommended that, as a matter of urgency, these issues be examined, particularly within the context of self-care in diabetes. Diabet. Med. **, ***,*** (2003) [source] Genome-wide association studies for discrete traitsGENETIC EPIDEMIOLOGY, Issue S1 2009Duncan C. Thomas Abstract Genome-wide association studies of discrete traits generally use simple methods of analysis based on ,2 tests for contingency tables or logistic regression, at least for an initial scan of the entire genome. Nevertheless, more power might be obtained by using various methods that analyze multiple markers in combination. Methods based on sliding windows, wavelets, Bayesian shrinkage, or penalized likelihood methods, among others, were explored by various participants of Genetic Analysis Workshop 16 Group 1 to combine information across multiple markers within a region, while others used Bayesian variable selection methods for genome-wide multivariate analyses of all markers simultaneously. Imputation can be used to fill in missing markers on individual subjects within a study or in a meta-analysis of studies using different panels. Although multiple imputation theoretically should give more robust tests of association, one participant contribution found little difference between results of single and multiple imputation. Careful control of population stratification is essential, and two contributions found that previously reported associations with two genes disappeared after more precise control. Other issues considered by this group included subgroup analysis, gene-gene interactions, and the use of biomarkers. Genet. Epidemiol. 33 (Suppl. 1):S8,S12, 2009. © 2009 Wiley-Liss, Inc. [source] Construction of periventricular white matter hyperintensity maps by spatial normalization of the lateral ventriclesHUMAN BRAIN MAPPING, Issue 7 2009Cynthia Jongen Abstract Subcortical and periventricular white matter hyperintensities (WMHs) may have different associations with cognition and pathophysiology. The aim of the present study is to develop an automated method for construction of periventricular WMH maps that enables the analysis of between-group differences in WMH location and characteristics in the periventricular region without the requirement of prior boundary definition. To avoid influence of WMHs on spatial normalization, a reference image of the lateral ventricles was constructed based on images of 24 subjects. Construction was not biased to a single subject. WMHs were segmented by k-nearest neighbor-based classification of magnetic resonance inversion recovery and fluid attenuated inversion recovery images. Cerebrospinal fluid segmentations of individual subjects were nonrigidly mapped to the reference image of the lateral ventricles. The subject's WMHs were transformed to the reference space accordingly. Spatial normalization accuracy was validated using measures of overlap and of displacement relative to the boundary of the lateral ventricles. After spatial normalization, the boundaries of the lateral ventricles closely matched the reference image and in an area of ,1 cm around the lateral ventricles the relative displacement was less than 1 mm. To illustrate the method, it was applied to 61 patients with Type 2 diabetes and 26 control subjects, whereupon periventricular WMH maps were constructed and compared. The proposed method is particularly suited to analyze WMH distribution differences at the level of the lateral ventricles between large groups of patients. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [source] Comparing MEG and fMRI views to naming actions and objectsHUMAN BRAIN MAPPING, Issue 6 2009Mia Liljeström Abstract Most neuroimaging studies are performed using one imaging method only, either functional magnetic resonance imaging (fMRI), electroencephalography (EEG), or magnetoencephalography (MEG). Information on both location and timing has been sought by recording fMRI and EEG, simultaneously, or MEG and fMRI in separate sessions. Such approaches assume similar active areas whether detected via hemodynamic or electrophysiological signatures. Direct comparisons, after independent analysis of data from each imaging modality, have been conducted primarily on low-level sensory processing. Here, we report MEG (timing and location) and fMRI (location) results in 11 subjects when they named pictures that depicted an action or an object. The experimental design was exactly the same for the two imaging modalities. The MEG data were analyzed with two standard approaches: a set of equivalent current dipoles and a distributed minimum norm estimate. The fMRI blood-oxygen-level dependent (BOLD) data were subjected to the usual random-effect contrast analysis. At the group level, MEG and fMRI data showed fairly good convergence, with both overall activation patterns and task effects localizing to comparable cortical regions. There were some systematic discrepancies, however, and the correspondence was less compelling in the individual subjects. The present analysis should be helpful in reconciling results of fMRI and MEG studies on high-level cognitive functions. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] Spatiotemporal mapping of cortical activity accompanying voluntary movements using an event-related beamforming approachHUMAN BRAIN MAPPING, Issue 3 2006Douglas Cheyne Abstract We describe a novel spatial filtering approach to the localization of cortical activity accompanying voluntary movements. The synthetic aperture magnetometry (SAM) minimum-variance beamformer algorithm was used to compute spatial filters three-dimensionally over the entire brain from single trial neuromagnetic recordings of subjects performing self-paced index finger movements. Images of instantaneous source power ("event-related SAM") computed at selected latencies revealed activation of multiple cortical motor areas prior to and following left and right index finger movements in individual subjects, even in the presence of low-frequency noise (e.g., eye movements). A slow premovement motor field (MF) reaching maximal amplitude ,50 ms prior to movement onset was localized to the hand area of contralateral precentral gyrus, followed by activity in the contralateral postcentral gyrus at 40 ms, corresponding to the first movement-evoked field (MEFI). A novel finding was a second activation of the precentral gyrus at a latency of ,150 ms, corresponding to the second movement-evoked field (MEFII). Group averaging of spatially normalized images indicated additional premovement activity in the ipsilateral precentral gyrus and the left inferior parietal cortex for both left and right finger movements. Weaker activations were also observed in bilateral premotor areas and the supplementary motor area. These results show that event-related beamforming provides a robust method for studying complex patterns of time-locked cortical activity accompanying voluntary movements, and offers a new approach for the localization of multiple cortical sources derived from neuromagnetic recordings in single subject and group data. Hum. Brain Mapping 2005. © 2005 Wiley-Liss, Inc. [source] Simplified intersubject averaging on the cortical surface using SUMAHUMAN BRAIN MAPPING, Issue 1 2006Brenna D. Argall Abstract Task and group comparisons in functional magnetic resonance imaging (fMRI) studies are often accomplished through the creation of intersubject average activation maps. Compared with traditional volume-based intersubject averages, averages made using computational models of the cortical surface have the potential to increase statistical power because they reduce intersubject variability in cortical folding patterns. We describe a two-step method for creating intersubject surface averages. In the first step cortical surface models are created for each subject and the locations of the anterior and posterior commissures (AC and PC) are aligned. In the second step each surface is standardized to contain the same number of nodes with identical indexing. An anatomical average from 28 subjects created using the AC,PC technique showed greater sulcal and gyral definition than the corresponding volume-based average. When applied to an fMRI dataset, the AC,PC method produced greater maximum, median, and mean t -statistics in the average activation map than did the volume average and gave a better approximation to the theoretical-ideal average calculated from individual subjects. The AC,PC method produced average activation maps equivalent to those produced with surface-averaging methods that use high-dimensional morphing. In comparison with morphing methods, the AC,PC technique does not require selection of a template brain and does not introduce deformations of sulcal and gyral patterns, allowing for group analysis within the original folded topology of each individual subject. The tools for performing AC,PC surface averaging are implemented and freely available in the SUMA software package. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc. [source] Molecular imaging: The application of small animal positron emission tomographyJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S39 2002Douglas J. Rowland Abstract The extraordinary advances in genomic technologies over the last decade have led to the establishment of new animal models of disease. The use of molecular imaging techniques to examine these models, preferably with non-destructive imaging procedures, such as those offered by positron emission tomography (PET), are especially valuable for the timely advancement of research. With the use of small animal PET imaging it is possible to follow individual subjects of a sample population over an extended time period by using highly specific molecular probes and radiopharmaceuticals. In this Prospect small animal PET imaging will be described, specifically focusing on the current technologies, its applications in molecular imaging and the logistics of performing small animal PET. J. Cell. Biochem. Suppl. 39: 110,115, 2002. © 2002 Wiley-Liss, Inc. [source] Comparison of phosphocreatine concentration in the human masseter and medial pterygoid muscles by 31P-CSIJOURNAL OF ORAL REHABILITATION, Issue 11 2001T. Kanayama The aim of this study is to compare phosphocreatine (PCr) concentrations of human masseter and medial pterygoid muscles by a recently developed localized magnetic resonance spectroscopy (MRS) method, chemical shift imaging (CSI). The characteristic spectra of phosphorous metabolites including PCr and ,-ATP from the superficial part of the masseter (SM) and the deep part of the masseter (DM) and the medial pterygoid muscles (MPt) from 11 volunteers, 20,27-year-old were obtained. The study clearly demonstrated higher PCr/,-ATP in the SM and MPt than in the DM both in mean values (P < 0·01) and in individual subjects. The results indicate that SM and MPt are power producers. There were no significant differences in the mean values of the PCr/,-ATP ratios in SM and MPt, however, the PCr/,-ATP ratios varied individually and the subjects could be divided into three distinct groups: values of MPt higher than SM (group A, 4 subjects); values of MPt almost equal to SM (group B, 3 subjects); and values of MPt lower than SM (group C, 4 subjects). There appears to be a close relationship between the PCr content as determined in the groups here and occlusal guidance. [source] Quantitative study of bite force during sleep associated bruxismJOURNAL OF ORAL REHABILITATION, Issue 5 2001K. Nishigawa Nocturnal bite force during sleep associated bruxism was measured in 10 subjects. Hard acrylic dental appliances were fabricated for the upper and lower dentitions of each subject. Miniature strain-gauge transducers were mounted to the upper dental appliance at the right and left first molar regions. In addition, thin metal plates that contact the strain-gauge transducers were attached to the lower dental appliance. After a 1-week familiarization with the appliances, nocturnal bite force was measured for three nights at the home of each subject. From the 30 recordings, 499 bruxism events that met the definition criteria were selected. The above described system was also used to measure the maximum voluntary bite forces during the daytime. The mean amplitude of detected bruxism events was 22·5 kgf (s.d. 13·0 kgf) and the mean duration was 7·1 s (s.d. 5·3 s). The highest amplitude of nocturnal bite force in individual subjects was 42·3 kgf (15·6,81·2 kgf). Maximum voluntary bite force during the daytime was 79·0 kgf (51·8,99·7 kgf) and the mean ratio of nocturnal/daytime maximum bite force was 53·1% (17·3,111·6%). These data indicate that nocturnal bite force during bruxism can exceed the amplitude of maximum voluntary bite force during the daytime. [source] Relationship between the prognosis of periodontitis and occlusal force during the maintenance phase , a cohort studyJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2010N. Takeuchi Takeuchi N, Ekuni D, Yamamoto T, Morita M. Relationship between the prognosis of periodontitis and occlusal force during the maintenance phase , a cohort study. J Periodont Res 2010; 45: 612,617. © 2010 John Wiley & Sons A/S Background and Objective:, Few studies have longitudinally investigated the relationship between periodontal disease progression and occlusal factors in individual subjects during the maintenance phase of periodontal therapy. The aim of this cohort study was to investigate the relationship between biting ability and the progression of periodontal disease in the maintenance phase. Material and Methods:, A total of 194 patients were monitored for 3 years during the maintenance phase of periodontal therapy. The subjects with disease progression (Progress group) were defined based on the presence of , 2 teeth demonstrating a longitudinal loss of proximal attachment of , 3 mm or tooth-loss experience as a result of periodontal disease during the study period. The subjects with high occlusal force were diagnosed as men who showed an occlusal force of more than 500 N and women who showed an occlusal force of more than 370 N. The association between biting ability and the progression of periodontitis was investigated using logistic regression analysis. Results:, There were 83 subjects in the Progress group and 111 subjects in the Non-progress group. A backward, stepwise logistic regression model showed that the progression of periodontal disease was significantly associated with the presence of one or more teeth with a high clinical attachment level (CAL) of , 7 mm (odds ratio: 2.397; 95% confidence interval: 1.306,4.399) (,p = 0.005) and low occlusal force (odds ratio: 2.352; 95% confidence interval: 1.273,4.346) (,p = 0.006). Conclusion:, The presence of one or more teeth with a high CAL of , 7 mm and low occlusal force might be possible risk factors for periodontal progression in the maintenance phase of periodontal therapy. [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] MEASUREMENT OF BITING VELOCITIES AT PREDETERMINED AND INDIVIDUAL CROSSHEAD SPEED INSTRUMENTAL IMITATIVE TESTS FOR PREDICTING SENSORY HARDNESS OF GELATIN GELSJOURNAL OF SENSORY STUDIES, Issue 2 2005M. FINNEY ABSTRACT Jaw movements during the act of biting were measured for seven subjects trained in descriptive analysis using an electrognathograph. The effectiveness of instrumental imitative tests performed at predefined and individual crosshead speeds (matching velocities measured in vivo) to predict the perception of hardness in 14 gelatin gels was assessed. For all seven subjects, the perception of hardness was adequately described by imitative instrumental tests performed with dental replicas of individual subjects (0.88 < R < 0.97). For some of the subjects, tests performed at crosshead speeds matching biting speeds improved the instrumental prediction of hardness, suggesting that biting velocity is an important aspect of the perception of hardness in food. [source] Cortical locations of maximal spindle activity: magnetoencephalography (MEG) studyJOURNAL OF SLEEP RESEARCH, Issue 2 2009VALENTINA GUMENYUK Summary The aim of this study was to determine the main cortical regions related to maximal spindle activity of sleep stage 2 in healthy individual subjects during a brief morning nap using magnetoencephalography (MEG). Eight volunteers (mean age: 26.1 ± 8.7, six women) all right handed, free of any medical psychiatric or sleep disorders were studied. Whole-head 148-channel MEG and a conventional polysomnography montage (EEG; C3, C4, O1 and O2 scalp electrodes and EOG, EMG and ECG electrodes) were used for data collection. Sleep MEG/EEG spindles were visually identified during 15 min of stage 2 sleep for each participant. The distribution of brain activity corresponding to each spindle was calculated using a combination of independent component analysis and a current source density technique superimposed upon individual MRIs. The absolute maximum of spindle activation was localized to frontal, temporal and parietal lobes. However, the most common cortical regions for maximal source spindle activity were precentral and/or postcentral areas across all individuals. The present study suggests that maximal spindle activity localized to these two regions may represent a single event for two types of spindle frequency: slow (at 12 Hz) and fast (at 14 Hz) within global thalamocortical coherence. [source] MEASUREMENT OF BITING VELOCITIES, AND PREDETERMINED AND INDIVIDUAL CROSSHEAD SPEED INSTRUMENTAL IMITATIVE TESTS FOR PREDICTING CHEESE HARDNESSJOURNAL OF TEXTURE STUDIES, Issue 1 2002J.-F. MEULLENET ABSTRACT Average first bite velocities of ten cheeses were measured for seven subjects trained in descriptive analysis using an electrognathograph. The effectiveness of instrumental imitative tests performed at predefined and individual crosshead speeds (matching velocities measured in vivo) to predict hardness perception of cheeses were assessed. For five of the seven subjects, the perception of hardness was adequately described by imitative instrumental tests performed with dental replicas of individual subjects. For some of the subjects (2 of 5), individual crosshead speed testing significantly improved the instrumental prediction of hardness. For other subjects, the instrumental test method did not seem to greatly influence the results. [source] Recognition of coagulation factor VIII by CD4+ T cells of healthy humansJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2003G-L. Hu Summary., Hemophilia A patients treated with coagulation factor (F)VIII may develop an anti-FVIII immune response. Anti-FVIII antibodies may occur also in healthy subjects. To understand the extent to which an immune response to FVIII occurs in healthy subjects, we investigated the proliferative response of blood CD4+ T cells from 90 blood donors to FVIII and to pools of overlapping synthetic peptides spanning the sequences of individual FVIII domains (A1,A3, C1,C2). Most subjects responded to FVIII and several FVIII domains. Men had stronger responses to FVIII than women, and older subjects than younger subjects. The domain-induced responses were weaker than the FVIII-induced responses, yet their intensity in individual subjects correlated with that of the response to FVIII. We examined whether Th1 and/or Th2 cells responded to FVIII in 68 subjects, by determining the CD4+ T cells that secreted interferon-, (IFN-,) or interleukin (IL)-5 after stimulation with FVIII: 25 subjects had FVIII-specific IFN-,-secreting cells, and seven of them had also FVIII-specific IL-5-secreting cells. None had only IL-5-secreting cells. Thus, a CD4+ T cell response to FVIII, which first involves Th1 cells, is common among subjects with a normal procoagulant function. [source] Dose-response relationship of rocuronium: A comparison of electromyographic vs. acceleromyographic-derived valuesACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2005A. F. Kopman Background: Acceleromyography (AMG) is being employed with increasing frequency as a research tool. However, there is almost no information available regarding the accuracy of values for drug potency obtained using AMG. This study was an attempt to determine if AMG-derived ED50/95 values are interchangeable with those measured with a more traditional neuromuscular monitor. Methods: Thirty adult patients were studied. Anesthesia was induced and maintained with N20, propofol, and supplementation opioid. Tracheal intubation was accomplished without muscle relaxants. Simultaneous ipsilateral AMG and EMG responses to 0.10 Hz stimulation was recorded. Following instrument calibrations, a single dose of rocuronium was administered. The first patient received a bolus of 0.17 mg kg,1 of rocuronium. Using the Hill equation with a postulated slope of 4.50, the ED50 was calculated. The second subject received a dose which approximated the calculated ED50 for patient no. 1. Successive subjects were given a dose based on the running average of the estimated ED50. Results: The AMG-derived ED50/95 values for rocuronium (0.163 ± 0.055 and 0.314 ± 0.105 mg mg,1) were virtually identical to those established using EMG (0.159 ± 0.043 and 0.306 ± 0.084 mg kg,1). While mean peak twitch depression (,T1) was the same in both groups for individual subjects ,T1 differed by ± 20% (95% confidence interval). Discussion: Acceleromyography-derived twitch heights for individual patients are not necessarily interchangeable with information obtained using electromyography. Nevertheless, acceleromyography appears to be a valid methodology for determining the drug potency when a population rather than an individual subject is being studied. [source] Linearity and reliability of the mechanomyographic amplitude versus dynamic torque relationships for the superficial quadriceps femoris musclesMUSCLE AND NERVE, Issue 3 2010Matthew S. Stock MS Abstract The purpose of this investigation was to examine the linearity and reliability of the mechanomyographic (MMG) amplitude versus dynamic torque relationships for the vastus lateralis (VL), rectus femoris (RF), and vastus medialis (VM) muscles. Nine healthy men and 11 healthy women performed submaximal to maximal, concentric, isokinetic muscle actions of the leg extensors at 30° s,1 on two occasions. Surface MMG signals were detected from the VL, RF, and VM of the dominant thigh during both trials. The ranges of the coefficients of determination for the MMG amplitude versus dynamic torque relationships were 0.01,0.94 for the VL, 0.01,0.84 for the RF, and 0.19,0.96 for the VM. The intraclass correlation coefficients for the linear MMG amplitude versus torque slope coefficients were 0.823 (VL), 0.792 (RF), and 0.927 (VM). These results indicate that, when analyzed for individual subjects, the MMG amplitude versus dynamic torque relationships demonstrated inconsistent linearity. When using MMG in the clinical setting, dynamic muscle actions of the superficial quadriceps femoris muscles do not appear to be appropriate for assessing changes in muscle function during strength training. Muscle Nerve, 2009 [source] Steady-State versus Non-Steady-State QT-RR Relationships in 24-hour Holter RecordingsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 3 2000GILLES LANDE The aim of the present study was to investigate the QT-RR interval relationship in ambulatory ECG recordings with special emphasis on the physiological circumstances under which the QT-RR intervals follow a linear relation. Continuous ECG recordings make it possible to automatically measure QT duration in individual subjects under various physiological circumstances. However, identification of QT prolongation in Holter recordings is hampered by the rate dependence of QT duration. Comparison of QT duration and QT interval rate dependence between different individuals implies that the nature of the QT-RR relationship is defined in ambulatory ECG. Holter recordings were performed in healthy volunteers at baseline and after administration of dofetilide, a Class III antiarrhythmic drug. After dofetilide, beat-to-beat automated QT measurements on Holter tapes were compared with manually measured QT intervals on standard ECGs matched by time. The QT-RR relationship was analyzed at baseline in individual and group data during three different periods: 24-hour, daytime, and nighttime. Data were collected under steady-state or non-steady-state conditions of cycle length and fitted with various correction formulae. Our study demonstrated an excellent agreement between manually and automated measurements. The classic Bazett correction formula did not fit the QT-RR data points in individual or group data. When heart beats were selected for a steady rhythm during the preceding minute, QT-RR intervals fit a linear relationship during the day and night periods, but not during the 24-hour period in both individual and group data. In contrast, in the absence of beat selection, data fit a more complex curvilinear relationship irrespective of the period. Our study provides the basis for comparison of QT interval durations and QT-RR relationships between individuals and between groups of subjects. [source] The reproducibility of ethnic differences in the proportional awake,sleep blood pressure decline among womenAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2010Helene M. Van Berge-Landry A growing body of evidence indicates that African Americans (AA), on average, have a smaller proportional decline in blood pressure (BP) from waking to sleep than European Americans (EA), but this difference is largely based on correlational data from a single assessment day. The persistence of this difference over repeated sampling is not well established. The purpose of this study was to evaluate whether ethnic differences in the awake,sleep BP decline between AA and EA persisted over three monthly assessments. The subjects were 47 AA (age = 39.7 ± 8.7) and 92 EA (age = 37.4 ± 9.2) normotensive women. Subjects had 24-h ambulatory BP monitoring done on midweek workdays at 1-month intervals for three consecutive months. The proportional decline in BP was calculated as follows: (average awake , average sleep)/average sleep. The persistence of ethnic differences was evaluated using repeated-measures ANCOVA and by examining Bland,Altman plots. The ANCOVA results revealed that overall, the proportional decline of AA women was less than that of EA women for both SBP (P < 0.038) and DBP (P < 0.083), consistent with previous research, and that there were also no significant ethnic differences by monthly assessment. Bland,Altman plots revealed that overall and by ethnicity, the proportional decline in BP among individual subjects over the 3 months was also reproducible. These results suggest that the ethnic difference in awake,sleep BP between AA and EA women persists over time and that the awake,sleep decline in BP among individuals, whether AA or EA, is also reproducible. Am. J. Hum. Biol., 2010. © 2009 Wiley-Liss, Inc. [source] Dynamics and Rate-Dependence of the Spatial Angle between Ventricular Depolarization and Repolarization Wave Fronts during Exercise ECGANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2010Tuomas Kenttä M.Sc. Background: QRS/T angle and the cosine of the angle between QRS and T-wave vectors (TCRT), measured from standard 12-lead electrocardiogram (ECG), have been used in risk stratification of patients. This study assessed the possible rate dependence of these variables during exercise ECG in healthy subjects. Methods: Forty healthy volunteers, 20 men and 20 women, aged 34.6 ± 3.4, underwent an exercise ECG testing. Twelve-lead ECG was recorded from each test subject and the spatial QRS/T angle and TCRT were automatically analyzed in a beat-to-beat manner with custom-made software. The individual TCRT/RR and QRST/RR patterns were fitted with seven different regression models, including a linear model and six nonlinear models. Results: TCRT and QRS/T angle showed a significant rate dependence, with decreased values at higher heart rates (HR). In individual subjects, the second-degree polynomic model was the best regression model for TCRT/RR and QRST/RR slopes. It provided the best fit for both exercise and recovery. The overall TCRT/RR and QRST/RR slopes were similar between men and women during exercise and recovery. However, women had predominantly higher TCRT and QRS/T values. With respect to time, the dynamics of TCRT differed significantly between men and women; with a steeper exercise slope in women (women, ,0.04/min vs ,0.02/min in men, P < 0.0001). In addition, evident hysteresis was observed in the TCRT/RR slopes; with higher TCRT values during exercise. Conclusions: The individual patterns of TCRT and QRS/T angle are affected by HR and gender. Delayed rate adaptation creates hysteresis in the TCRT/RR slopes. Ann Noninvasive Electrocardiol 2010;15(3):264,275 [source] Effect of low frequency modulated microwave exposure on human EEG: Individual sensitivityBIOELECTROMAGNETICS, Issue 7 2008Hiie Hinrikus Abstract The aim of this study was to evaluate the effect of modulated microwave exposure on human EEG of individual subjects. The experiments were carried out on four different groups of healthy volunteers. The 450 MHz microwave radiation modulated at 7 Hz (first group, 19 subjects), 14 and 21 Hz (second group, 13 subjects), 40 and 70 Hz (third group, 15 subjects), 217 and 1000 Hz (fourth group, 19 subjects) frequencies was applied. The field power density at the scalp was 0.16 mW/cm2. The calculated spatial peak SAR averaged over 1 g was 0.303 W/kg. Ten cycles of the exposure (1 min off and 1 min on) at fixed modulation frequencies were applied. All subjects completed the experimental protocols with exposure and sham. The exposed and sham-exposed subjects were randomly assigned. A computer also randomly assigned the succession of modulation frequencies. Our results showed that microwave exposure increased the EEG energy. Relative changes in the EEG beta1 power in P3-P4 channels were selected for evaluation of individual sensitivity. The rate of subjects significantly affected is similar in all groups except for the 1000 Hz group: in first group 3 subjects (16%) at 7 Hz modulation; in second group 4 subjects (31%) at 14 Hz modulation and 3 subjects (23%) at 21 Hz modulation; in third group 3 subjects (20%) at 40 Hz and 2 subjects (13%) at 70 Hz modulation; in fourth group 3 subjects (16%) at 217 Hz and 0 subjects at 1000 Hz modulation frequency. Bioelectromagnetics 29:527,538, 2008. © 2008 Wiley-Liss, Inc. [source] Time-Varying Functional Regression for Predicting Remaining Lifetime Distributions from Longitudinal TrajectoriesBIOMETRICS, Issue 4 2005Hans-Georg Müller Summary A recurring objective in longitudinal studies on aging and longevity has been the investigation of the relationship between age-at-death and current values of a longitudinal covariate trajectory that quantifies reproductive or other behavioral activity. We propose a novel technique for predicting age-at-death distributions for situations where an entire covariate history is included in the predictor. The predictor trajectories up to current time are represented by time-varying functional principal component scores, which are continuously updated as time progresses and are considered to be time-varying predictor variables that are entered into a class of time-varying functional regression models that we propose. We demonstrate for biodemographic data how these methods can be applied to obtain predictions for age-at-death and estimates of remaining lifetime distributions, including estimates of quantiles and of prediction intervals for remaining lifetime. Estimates and predictions are obtained for individual subjects, based on their observed behavioral trajectories, and include a dimension-reduction step that is implemented by projecting on a single index. The proposed techniques are illustrated with data on longitudinal daily egg-laying for female medflies, predicting remaining lifetime and age-at-death distributions from individual event histories observed up to current time. [source] Desloratadine dose selection in children aged 6 months to 2 years: comparison of population pharmacokinetics between children and adultsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2007Samir K. Gupta What is already known about this subject ,,According to recent literature, the pathophysiologies of allergic rhinitis and chronic idiopathic urticaria are thought to be similar in adults and children. In addition, the response to antihistamine treatment is similar in adults and children, suggesting a similar concentration-response relationship. ,,However, an appropriate dose selection and the pharmacokinetics of desloratadine in children of ,6 months,,2 years old have never been addressed in the literature. What this study adds ,,This study demonstrated that desloratadine syrup offers a safe treatment option for allergic conditions in young children. ,,A suitable dose for children aged ,6 months,<1 year is 1.0 mg, while the corresponding predicted dose for children aged ,1 year,,2 years is 1.25 mg. These paediatric doses yielded similar systemic desloratadine exposures (AUC) to those seen with a typical adult dose of 5.0 mg. Aims The aim of this study was to identify the dose of desloratadine in children aged ,6 months,,2 years that would yield a single-dose target exposure (AUC) comparable with that in adults taking 5 mg desloratadine as syrup. Methods In a phase 1, single-dose, open-label, pharmacokinetic study in 58 children aged ,6 months,<1 year and ,1 year,,2 years were randomly assigned to desloratadine syrup 0.625 mg (1.25 ml) and 1.25 mg (2.5 ml), respectively. Because the volume of blood that could be collected from individual subjects was limited, a population pharmacokinetic approach was used to estimate the pharmacokinetics of desloratadine. Safety was assessed based on results of screening and postdose physical examinations, laboratory safety tests, vital signs, and adverse events. Results The apparent clearance (CL/F) of desloratadine, population estimate (%CV), in children aged ,6 months,<1 year was 27.8 l h,1 (35) and corresponding values in children ,1 year,,2 years was 35.5 l h,1 (51), compared with 137 l h,1 (58) for adults. The CL/F ratios (children to adults) indicated that doses of 1 mg for ,6 months,<1 year and 1.25 mg for ,1 year,,2 years would result in similar systemic exposure to that observed in adults receiving the recommended 5 mg dose. Desloratadine was well tolerated with no safety issues. Conclusions Doses of 1.0 and 1.25 mg in children aged ,6 months,,2 years should result in an exposure to desloratadine similar to that of adults receiving doses of 5 mg. [source] | ||||||||||||||||||||||||||||