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Large Individual Variation (large + individual_variation)
Selected AbstractsEffect of lansoprazole and rabeprazole on tacrolimus pharmacokinetics in healthy volunteers with CYP2C19 mutationsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2004Fumio Itagaki The aim of this study was to investigate the effects of the proton pump inhibitors (PPIs), lansoprazole and rabeprazole, on tacrolimus pharmacokinetics in healthy volunteers with mutations in the cytochrome P450 (CYP) 2C19 gene (CYP2C19). An open-label crossover study was performed with 19 healthy subjects. Tacrolimus (2 mg) was administered orally with and without lansoprazole (30 mg per day for 4 days) or rabeprazole (10 mg per day for 4 days). Blood concentrations of tacrolimus were determined before and 1, 2, 4 and 8 h after dosing. Genotyping for CYP2C19 was conducted by a polymerase chain reaction-restriction fragment length polymorphism method. Coadministration of lansoprazole significantly decreased the oral tacrolimus clearance, resulting in an increase in the area under the blood concentration-time curve (AUC0,8) (control vs with lansoprazole: 29.7 ± 3.5 vs 44.1 ± 5.0 ng h mL,1, P<0.05). Large individual variation was observed in the effects of lansorazole on tacrolimus AUC0,8 owing to CYP2C19 genotype status. The percent change for tacrolimus AUC0,8 in subjects with and without CYP2C19 mutant alleles was 81% and 29%, respectively. Coadministration of rabeprazole also increased the mean AUC0,8 of tacrolimus, but the difference was not statistically significant. These observations suggest that drug interaction between tacrolimus and lansoprazole occurs in subjects with higher lansoprazole blood concentrations corresponding to CYP2C19 genetic status. In contrast, rabeprazole has minimal effect on tacrolimus pharmacokinetics regardless of CYP2C19 genotype status. [source] Lifetime reproductive success in relation to morphology in the house sparrow Passer domesticusJOURNAL OF ANIMAL ECOLOGY, Issue 4 2004Henrik Jensen Summary 1In this study we relate variation in lifetime reproductive success (LRS) of male and female house sparrows Passer domesticus to morphological characteristics. 2Our analyses demonstrated no sex-specific difference in the distribution of LRS. The variance in LRS was influenced mainly by variation in individual annual reproductive success, and to a lesser extent by variation in individual lifespan. 3Phenotypic traits explained a significant proportion of the variation in LRS in males, but not in females. The effect of male morphology on LRS operated mainly through an effect on the number of recruiting daughters. 4The size of the patch of black feathers on the chest of males (badge size) and male bill length were both positively associated with LRS. Lifespan and bill length were positively related and reproductive success increased with badge size. In females, number of recruiting daughters was positively related to bill length, body mass and body condition index due to the positive effect of these traits on annual production of daughters. 5These results indicate that identifying factors causing the large individual variation in LRS, which is likely to be closely related to fitness, will be important to understand microevolutionary processes in this metapopulation, and hence their demographic feedbacks. [source] A reliable externally fixated murine femoral fracture model that accounts for variation in movement between animalsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2003Chris K. Connolly Abstract Fifty-two CFLP mice had an open femoral diaphyseal osteotomy held in compression by a four-pin external fixator. The movement of 34 of the mice in their cages was quantified before and after operation, until sacrifice at 4, 8, 16 or 24 days. Thirty-three specimens underwent histomorphometric analysis and 19 specimens underwent torsional stiffness measurement. The expected combination of intramembranous and endochondral bone formation was observed, and the model was shown to be reliable in that variation in the histological parameters of healing was small between animals at the same time point, compared to the variation between time-points. There was surprisingly large individual variation in the amount of animal movement about the cage, which correlated with both histomorphometric and mechanical measures of healing. Animals that moved more had larger external calluses containing more cartilage and demonstrated lower torsional stiffness at the same time point. Assuming that movement of the whole animal predicts, at least to some extent, movement at the fracture site, this correlation is what would be expected in a model that involves similar processes to those in human fracture healing. Models such as this, employed to determine the effect of experimental interventions, will yield more information if the natural variation in animal motion is measured and included in the analysis. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Exercise tolerance and daily life in McArdle's diseaseMUSCLE AND NERVE, Issue 5 2005Karen Ollivier MSc Abstract McArdle's disease is a common disorder of muscle metabolism and is due to myophosphorylase deficiency. The major complaint of patients with this disease is effort intolerance. Although the clinical features of affected patients are well known, their daily lifestyle is not well documented. The main objective of this work was to assess their mean daily energy expenditure (DEE) and compare it with control subjects. Thirty patients and 87 control subjects completed a questionnaire. A 3-day self-record of daily physical activities was used to estimate the mean DEE for patients and control subjects. A separate section of the questionnaire was used to assess patients' clinical features and daily lifestyle. The DEE of patients (44.1 ± 6.9 kcal/kg) was not significantly different from control subjects (44.5 ± 5.6 kcal/kg). Half of the patients with McArdle's disease performed a daily physical leisure activity as sport, sometimes at a high level (17%). Despite large individual variation, physical abilities and patients' symptoms were negatively correlated. Physical leisure activity significantly decreased the sensation of muscle pain (P < 0.03). These findings show that patients with McArdle's disease do not have a strictly sedentary lifestyle. Moreover, physical exercise appears to have positive effects on the main clinical features, such as effort intolerance. Thus, regular, moderate physical activity may be beneficial in McArdle's disease. Muscle Nerve, 2005 [source] Determination of plasma vitamin C concentration in fattening cattleANIMAL SCIENCE JOURNAL, Issue 1 2003Lin HAIYING ABSTRACT Plasma vitamin C (ascorbic acid + dehydroascorbic acid) concentration is a good index of the nutritional status of vitamin C. However, the methodologies for storage and analyses have not been investigated in bovine plasma. The validity of an analytical method for bovine plasma using high performance liquid chromatography (HPLC) with a spectrophotometric detector was examined. Exogenous dehydroascorbic acid was almost completely converted to ascorbic acid during the preparation for analysis with a reducing reagent, dithioerythritol. The analytical recoveries of ascorbic acid were high. Ascorbic acid was not detected after treatment with ascorbic acid oxidase. Thus, the specificity of this method is considered to be high. Although vitamin C was stable in plasma treated by dithioerythritol at ,20°C for 6 days, vitamin C in untreated plasma significantly decreased during 3-day storage at ,20°C. These results indicate that the HPLC method is suitable for the determination of plasma vitamin C in cattle and that the storage conditions are important for determination of plasma vitamin C. Plasma vitamin C concentration ranged between 1.49 mg/L and 3.33 mg/L in fattening cattle. This result suggests that fattening cattle show large individual variation in plasma vitamin C concentration. [source] The wisdom behind third molar extractionsAUSTRALIAN DENTAL JOURNAL, Issue 4 2009S Kandasamy Abstract The literature pertaining to the extraction of third molars is extensive. There is a large individual variation and a multitude of practitioners' beliefs and biases relating to the extraction of especially asymptomatic and pathology free third molars. With the current emphasis in dentistry being placed on clinicians to make evidence-based decisions, the routine removal of third molars has been re-assessed and questioned. The purpose of this paper was to evaluate past and present knowledge of third molar extractions and relate it to logical considerations relevant to science and the evidence-based decision-making process. This paper endeavours to encourage and stimulate clinicians to re-evaluate their views on third molar extractions based on suggested guidelines and current evidence. [source] Extremely low frequency (ELF) electric and magnetic field exposure limits: Rationale for basic restrictions used in the development of an Australian standard,BIOELECTROMAGNETICS, Issue 6 2008Andrew W. Wood Abstract There are large disparities between basic restrictions for exposure to extremely low-frequency (0,3 kHz) Electric and Magnetic Fields set by two major international bodies. Both bodies agree that these basic restrictions should prevent neuro-stimulatory effects: the retinal phosphene at frequencies up to a few hundred Hertz and peripheral nervous stimulation (PNS) at higher frequencies. The disparity arises from differences in estimated thresholds and frequency dependence, and whether restrictions should be of tissue induced current density or electric field. This paper argues that the latter metric more directly relates to neurostimulatory processes. By analysing available literature, a threshold for retinal phosphenes occurrence is found to be 56 mV/m (95% Confidence Interval 2,1330 mV/m), with a characteristic frequency of 20 Hz. Similarly, the smallest PNS sensation threshold is identified at 2 V/m (characteristic frequency above 3 kHz). In the case of the former, the large range of uncertainty suggests a ,power of ten' value of 100 mV/m. For the latter, because of the small margin between sensation and pain threshold, and because of the large individual variation, the smallest estimate of sensation threshold (2 V/m) represents a basic restriction with precaution incorporated. Bioelectromagnetics 29:414,428, 2008. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||