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[The psychophysics of sweet taste. 8. Interindividual variability of differential findings].

Contribution to the psychophysics of sweet taste. Part 8. On the inter-individual variability of the difference sensitivity. The variability of sensitivity of volunteers is a considerable imponderability for the comparison of sensoric results. The paper deals with the quantitative determination of the different sensitivity of sweet taste of 132 persons, 38 men and 94 women at the age of 19 to 64 years, using a statistically defined method. The numbers of errors are estimated for each person by means of one test difference of two saccharose concentrations using 10 pairs of comparisons and 4 runs. The average number of error of 10 comparisons corresponds to the individual measure of sensitivity. The medium value of the total distribution is 1.54 and the standard deviation is 1.19 errors. The value is only less above the binomial calculated number. In random test women show in comparison to men a significant higher variance at the statistical identical mean. A variance analysis based on the cutting of the distribution edges in the range of 0.5 to 4.0 errors can detect high significantly the steady learning effect of the volunteers during the runs. The method is applicable to determine classified subjective characteristics. The calculations of necessary group numbers for such experiments on the base of binomial distribution are discussed.

Adult↗

Definition of chemiluminescence and superoxide production responses of bovine neutrophils to selected soluble and particulate stimulants, and comparisons with the responses to Pasteurella haemolytica.

We defined methods for use of luminol-dependent chemiluminescence (LDCL) and superoxide anion (O2-) production as parameters of the oxidative metabolism of neutrophils isolated from 1.5- to 5-week-old neonatal calves. We determined how variations in blood sample handling, agonist preparation, individual variability, and age of calves influenced the LDCL and O2- responses to certain agonists, and defined concentrations of soluble and particulate agonists that maximally stimulated the oxidative metabolism of bovine neutrophils. Oxidative responses, particularly LDCL, were characterized by marked day-to-day variability, differed greatly within and between calves, were partially age-dependent, and were partially dependent on the individual agonist. Superoxide anion production had substantially less variability. We compared the in vitro oxidative (LDCL and O2-) responses of neutrophils isolated from neonatal calves stimulated by defined concentrations of the agonists--latex, phorbol myristate acetate, calcium ionophore, and opsonized zymosan--with responses to formylated oligopeptides and zymosan-activated serum, and to live, dead, live opsonized, and dead opsonized Pasteurella haemolytica organisms. Opsonization of particulates, pathogenic or nonpathogenic, enhanced the LDCL and O2- responses of stimulated neutrophils although P haemolytica was a less potent stimulant of oxidative functions than were nonbiological agonists. We conclude that the generation of reactive oxygen species by bovine neutrophils in response to P haemolytica is highly dependent on the presence of opsonins and is greatly enhanced in live vs killed bacteria. Furthermore, the in vitro generation of reactive oxygen species, including O2- by stimulated neutrophils, may be of biologic importance if similar events occur in vivo, and could have a major role in the pathogenesis of the acute lung injury associated with pneumonic pasteurellosis.

Adjuvants, Immunologic↗

P300 after minor head injury (a follow-up examination).

BACKGROUND AND METHODS: The aim of the study was to examine whether--like in severe head injuries--the endogenous evoked potential P300 is influenced by minor head injury (MHI) and how the eventual abnormalities develop within a follow-up period of 8 weeks after trauma. Therefore we examined the cognitive auditory evoked potential P300 (latency, amplitude), the neurologic state and the performance in psychometric testing (Mini-Mental-State, Number Connection test part A and B) in 15 patients within the first 24 hours as well as 1, 3 and 8 weeks after MHI. The P300 results were compared to the age-related normal ranges under consideration of the intra-individual variability. For both parameters normative values were established before in our own laboratory. RESULTS: For the patient group as a whole the mean values for P300 latency and amplitude were always within the age-related normal range and normal intra-individual long-term variability of healthy controls, respectively. Significant posttraumatic prolongations of P300 latency were exclusively observed in the only 20% of our patients with clinically suspected posttraumatic organic brain syndrome. These prolongations of latency decreased during follow-up and on the last examination the latencies were normalised. Compared to psychometric tests, P300 latency seems to be more sensitive in early detection of cerebral dysfunction. CONCLUSIONS: We conclude that, in contrast to severe head injury, in general the P300 is not affected by minor head injury. If there are clinical signs of organic brain syndrome following MHI posttraumatic prolongation of P300 latency is a marker of cerebral dysfunction and may serve as a valuable parameter for follow-up examination and documentation.

Adolescent↗

Standardized noninvasive assessment of myocardial free fatty acid kinetics by means of 15-(p-iodo-phenyl) pentadecanoic acid (123I-pPPA) scintigraphy: II. Clinical results.

Our results establish that myocardial regions supplied by a significantly stenosed coronary vessel can be distinguished with high statistical significance from healthy regions on account of changes in the myocardium/background ratio, i.e. a reduction of regional uptake of 15-(p-iodo-phenyl) pentadecanoic acid (pPPA). The statistical significance applies to patients with coronary artery disease (CAD), to all examined CAD areas without areas of infarction as well as to infarcted regions. Our results also confirm the suitability of labelled fatty acids, such as pPPA, for the visualization of damaged myocardial regions. The results further indicate that pPPA practically is of comparable value to 201Tl with regard to their respective qualities as 'static' imaging agents for the heart muscle. This study, with the help of a simultaneous analysis of regional myocardial perfusion rates (rMBF) and of a parameter for the metabolism of fatty acids, practised here for the first time, could demonstrate interindividual differences between patients and groups of patients with a correlation between perfusion and the utilization of pPPA in patients with CAD. The reciprocal of the rMBF, the mean transit time (MTT), was significantly prolonged after stress in patients with CAD (P less than 0.05), suggesting impaired 'microcirculation' in the patient group. The determination of elimination half-lives (T1/2) contributes little if any information towards delineation of cardiac disease entities. The wide overlap of T1/2 values between various clinical syndromes and entities with extreme standard deviations remained an annoying problem in our studies. Nevertheless, certain trends in T1/2 behaviour could be recorded, but they did not yield any statistical significances, because of the high degree of individual variability. A considerable variability of T1/2 values among healthy controls was recorded as well as intra-individually in different regions of the heart muscle. The wide range of 'normal' values rendered statistical evaluation almost, if not entirely, impossible. It appears that the high degree of variability results amongst others, from technical shortcomings in the external recording instruments, i.e. gamma cameras, as well as from the presence of interfering alternate substrates such as glucose and lactate. Nevertheless, the wide range of measured results in healthy control subjects suggests the presence of a considerable regional intra-individual heterogeneity of cardiac substrate metabolism. One must therefore accept, at least in our opinion, that T1/2 values are not sufficiently reliable as an indicator of myocardial metabolism and are of little value with respect to clinical diagnostic considerations and to prognosis as well. Possible explanations for this finding are offered and discussed in this paper.

Adult↗

Variability of fMRI activation during a phonological and semantic language task in healthy subjects.

Assessing inter-individual variability of functional activations is of practical importance in the use of functional magnetic resonance imaging (fMRI) in a clinical context. In this fMRI study we addressed this issue in 30 right-handed, healthy subjects using rhyme detection (phonologic) and semantic categorization tasks. Significant activations, found mainly in the left hemisphere, concerned the inferior frontal gyrus, the superior/middle temporal gyri, the prefrontal cortex, the inferior parietal lobe, the superior parietal lobule/superior occipital gyrus, the pre-central gyrus, and the supplementary motor area. Intensity/spatial analysis comparing activations in both tasks revealed an increased involvement of frontal regions in the semantic task and of temporo-parietal regions in the phonologic task. The frequency of activation analyzed in nine regional subdivisions revealed a high inter-subject variability but showed that the most frequently activated regions were the inferior frontal gyrus and the prefrontal cortex. Laterality indices, strongly lateralizing in both tasks, were slightly higher in the semantic (0.76 +/- 0.19) than the phonologic task (0.66 +/- 0.27). Frontal dominance indices (a measure of frontal vs. posterior left hemisphere dominance) indicated more robust frontal activations in the semantic than the phonologic task. Our study allowed the characterization of the most frequently involved foci in two language tasks and showed that the combination of these tasks constitutes a suitable tool for determining language lateralization and for mapping major language areas.

Adult↗

The role of pharmacogenetically-variable cytochrome P450 enzymes in drug abuse and dependence.

The risk of drug dependence is determined by the interaction of drug, individual and environment. 'Pharmacogenetics' is the study of the influence of heredity on the response to drugs and their fate in the body; these studies aim to improve the understanding of inter-individual variability in drug response. The authors have applied this research approach to the study of drug metabolism and dependence. Specifically the interaction of genetically variable hepatic cytochrome P450 (CYP) enzymes and their effect on self-administration of drugs has been examined. Many drugs of abuse are substrates (e.g., amphetamines, codeine, nicotine) or inhibitors (e.g., (-)-cocaine) of polymorphic CYPs. Drug metabolism by genetically polymorphic enzymes can have significant clinical implications relating to drug toxicity, therapeutic failure, drug-drug interactions, disease susceptibility and abuse liability. There is good evidence that drug metabolism by genetically variable CYPs can influence the risk of drug dependence, the amount of drug consumed by dependent individuals and some of the toxicities associated with drug-taking behavior. It is anticipated that pharmacogenetics will be used to identify individuals at a greater risk for specific drug dependencies, provide information that can lead to novel treatment and prevention approaches as well as provide guidance for individualization of treatment choice.

Animals↗

Seasonal changes in power of competitive cyclists: implications for monitoring performance.

Sport scientists should consider seasonal trends and individual variability in performance when using tests to track performance changes resulting from training or other medium-term interventions with individuals or in research studies. We report here the seasonal changes and variability in power of 12 male competitive cyclists, who performed laboratory tests of incremental peak and 4-km mean power measured with three ergometers simultaneously in each of five sessions during three phases (base, pre-comp, comp) of a season. Repeated-measures analysis of log-transformed power provided mean percent changes in performance between phases and within-cyclist variability in performance expressed as coefficients of variation between sessions < or = 2 wk apart within a phase and between sessions 8 wk-12 wk apart in different phases. Peak power increased from the base phase to the pre-comp phase on average by 5.3%, and by a further 1.8% from pre-comp to comp phase; corresponding increases in 4-km mean power were 6.1% and 2.2% (90% likely limits all approximately +/-2.6%). The variabilities for peak and 4-km mean powers were 1.2%-1.8% for sessions separated by < or = 2 wk and 2.0%-2.3% for sessions in pre-comp and comp phases, but increased to 3.4%-3.8% for sessions between the base and other phases (likely limits approximately (x/)/(1.6). Individual differences in the improvement in performance after the base phase evidently produced the greater variability between the base and the other phases. Interventions that might produce small but worthwhile changes in performance over a period of weeks-months need to be researched in pre-comp and comp phases, when the variability is small.

Adult↗

Stress, depression, and anxiety predict average symptom severity and daily symptom fluctuation in systemic lupus erythematosus.

Forty-one subjects diagnosed with systemic lupus erythematosus (SLE) were recruited from across the United States. Regressions were conducted to evaluate the relation among stress, depression, anxiety, anger, and SLE symptom complaints. Negative weighting of major life events predicted symptom history. Significant hierarchical regressions using negative weighting of major life events, impact of daily stress, depression, anxiety, and anger were found for severity of joint pain, abdominal distress, and rash. Analyses using 1-day-lagged predictors yielded similar results. Within-subject analyses suggested that there was much individual variability in the strength of the stress-illness relation. Thus, some individuals appeared to be stress responders, while others did not. Findings for impact of minor life events and depression were consistent across the different levels of analyses. It was concluded that stress, depression, anxiety, and anger are associated with, and may exacerbate, self-reported symptomatology of SLE patients.

Adult↗

Blood flow heterogeneity in the heart.

Local deposition density of microspheres is heterogeneous in histologically homogeneous myocardium under physiological conditions. The underlying biological heterogeneity must be distinguished from a methodological heterogeneity which depends preferentially on the number of microspheres injected, blood flow to a particular myocardial region and sample mass. As the variables space (spat), time (temp), and method (meth) are independent of each other, the observed (obs) variability may be approximated using the coefficients of variation (CV) of the individual variables: CVobs = (CV2spat+CV2temp+CV2meth)0.5. Studies in which these different variables have been quantified indicate that the largest fraction of the observed variability of microsphere deposition density is contributed by spatial flow heterogeneity which exists independent of the myocardial layer. Spatial flow heterogeneity increases with decreasing sample mass and decreasing mean flow. Fractal and autocorrelation analyses have shown that adjacent myocardial flows are spatially correlated and nonrandom. Local blood flow was shown to correlate with various metabolic and transport rates, while no differences were found between low and high flow regions with respect to several metabolic markers of tissue hypoxia. In conclusion, the evidence available to date indicates that 1) in histologically homogeneous myocardium there exists a spatial blood flow heterogeneity which 2) is temporally stable, 3) resolution dependent, 4) largely layer-independent, 5) nonrandom, and 6) related to local aerobic metabolism.

Aerobiosis↗

Hipocrates: a robust system for the control of neuromuscular blockade.

OBJECTIVE: Development of an automatic system (software package Hipocrates) for the control of neuromuscular blockade by continuous infusion of the non-depolarising types of muscle relaxant drugs presently used in anaesthesia, namely atracurium, cisatracurium, vecuronium and rocuronium. METHODS: Hipocrates incorporates control strategies based upon classical, adaptive and robust control, as well as a wide range of noise reduction techniques and on-line adaptation to patient-specific characteristics. Therefore, the system provides strong robustness to inter- and intra-individual variability of the patients responses or unexpected circumstances and adaptation to the individual requirements. RESULTS: The control system is easy to set up and to use in a clinical environment. It consists of a portable PC computer, a Datex AS/3 NMT sensor and a B/Braun compact perfusion pump. In the simulation mode the software package incorporates sophisticated generation of pharmacokinetic/pharmacodynamic models driven by simulated drug administration regimes (bolus, continuous infusion and a combination of both). CONCLUSIONS: Hipocrates is an advanced standalone application for the control of neuromuscular blockade with a friendly graphic interface. It has been extensively validated, and it can be used on patients undergoing surgery as well as for simulation studies. Therefore Hipocrates also provides an excellent environment for education and training purposes.

Anesthesia, General↗

The use of biomarkers in epidemiology: the example of bladder cancer.

Epidemiological studies have suggested that genetically based polymorphism for N-acetylation of arylamines might play an important role in the susceptibility to bladder cancer induction. However, these studies show large differences in the extent of such susceptibility. We have undertaken collaborative investigations (with IARC, MIT, NCI and NCTR) which couple internal dosimetry among smokers (measurement of hemoglobin and DNA adducts of arylamines) with the assessment of metabolic polymorphism. In one of these studies, hemoglobin adducts of 14 arylamines (including 2-naphthylamine and 4-aminobiphenyl) were analysed in a group of 86 subjects (smokers and non-smokers) in order to establish whether the inter-individual variability left unexplained by tobacco smoking could be attributed to differences in individual metabolic patterns. In another investigation on 100 smokers and non-smokers, metabolic polymorphism for N-acetylatransferase was assessed by measuring five different urinary metabolites of caffeine, after timed urine collection following coffee consumption. Arylamine-hemoglobin adducts were also measured. 4-Aminobiphenyl-hemoglobin adducts were found to be related to both the quantity and the type of tobacco smoked, as well as to the acetylator phenotype (independently of smoking habits).

Aminobiphenyl Compounds↗

Habituation of cortisol responses to repeated psychosocial stress-further characterization and impact of genetic factors.

Although a rapid response habituation to repeated stress exposure is a key characteristic of the hypothalamus-pituitary-adrenal (HPA) axis, several studies document a substantial inter-individual variability of such HPA response patterns. In order to further investigate the individual differences in the habituation of this important neuroendocrine system to psychosocial stress, 54 male twin pairs were exposed to moderate psychosocial stress on three occasions, each exposure separated by a 1-week interval. Additionally, an ACTH(1-24) stimulation test (1 microg) and a dexamethasone suppression test (0.5mg) were performed. Although on average the expected decrease of mean cortisol and ACTH responses across stress exposures was observed, only 52% of the subjects showed this well-documented general decline and almost 16% of the participants even showed a response sensitization across sessions. Furthermore, a weak habituation was related to low cortisol responses to both the first stress exposure as well as the ACTH challenge. Moreover, genetic analyses did not reveal any evidence for a substantial heritability of the individual cortisol response habituation or an association between this habituation and two common polymorphisms in the glucocorticoid receptor gene.

Adaptation, Physiological↗

Intestinal absorption of triglyceride and cholesterol. Dietary and pharmacological inhibition to reduce cardiovascular risk.

Triglycerides and cholesterol are important biological lipids, and their excessive intake in the diet is relevant to the development of two prevalent cardiovascular risk factors, obesity and hypercholesterolemia. Because most lipids are essentially water-insoluble molecules, their transport within and absorption from the aqueous medium of intestinal contents is rather complex. This takes place in a series of orderly and interrelated steps, including emulsification, hydrolysis by specific esterases, micellar transport, mucosal absorption, re-synthesis of parent molecules in enterocytes, and assembly with apolipoproteins and other molecules to form chylomicrons, the secretory product of intestinal cells. Many of these processes, however, are not well characterized at the molecular level. While in health the intestinal absorption of triglycerides is very efficient, the same does not apply to cholesterol absorption. Besides being generally inefficient, cholesterol absorption is highly variable, with a between-subject variability that depends in part on genetic factors and an intra-individual variability, which may be modulated by physiological and dietary conditions. All of the sequential steps in intestinal lipid absorption can be interfered with by dietary components or drugs and thus are potential therapeutic targets for inducing a controlled malabsorption of triglyceride, useful in the treatment of obesity, or for rendering cholesterol absorption even more inefficient in an attempt to lower blood cholesterol levels. Nevertheless, intestinally derived cholesterol available to the liver exerts complex feedback regulation on whole-body cholesterol homeostasis that limits the efficacy of cholesterol absorption inhibitors to lower blood cholesterol. This review focuses first on present knowledge of the physiology of intestinal fat absorption, necessary to understand the ways to manipulate it in order to obtain the desired effects on dietary triglyceride and cholesterol disposition. The second part discusses old, present and future ways, both dietary and pharmacological. of interfering with cholesterol and triglyceride absorption to reduce blood cholesterol and energy acquisition, respectively.

Animals↗

The immunobiology of gastrointestinal nematode infections in ruminants.

The major gastrointestinal nematode parasites of ruminants all belong to the Order Strongylida and the family Trichostrongyloidea. Despite this close evolutionary relationship, distinct differences exist in the microenvironmental niches occupied by the developmental stages of the various parasites, which may account for the variable susceptibility of the different parasite species to the immune effector mechanisms generated by the host. In addition, different manifestations of resistance have been observed against the adult and larval stages of the same parasite species, and even against the same parasite stage. In particular, both rapid and delayed rejection of infective larval stages of gastrointestinal nematode parasites has been documented. This review will give an overview of the various manifestations of resistance to gastrointestinal nematode parasites of ruminants, as well as the immune mechanisms and antigens associated with the generation of immunity by the ruminant hosts to these parasites. In addition, a working model is provided aimed at reconciling most of the present knowledge on the different immune responses generated during infection with the various parasite rejection profiles. Extrapolation of these results to field conditions will need to take into account the variability imposed by seasonal changes and management practices, as well as the individual variability in immune responsiveness present in outbred animal populations.

Animals↗

Antioxidant intervention does not affect the response of plasma erythropoietin to short-term normobaric hypoxia in humans.

Recent research has demonstrated that reactive oxygen species (ROS) participate in intracellular signaling processes initiated during hypoxia. We investigated the role of ROS in the response of plasma erythropoietin (Epo) to short-term normobaric hypoxia in humans. Twelve male subjects were exposed twice to 4 h of normobaric hypoxia (H; inspired oxygen fraction 12.5%) with a period of 6 wk between both experiments (H1 and H2). With the use of a randomized placebo-controlled crossover design, the subjects received orally a combination of the antioxidants all-rac-alpha-tocopherol (800 mg/day for 3 wk) and alpha-lipoic acid (600 mg/day for 2 wk) or placebo before H1 and H2, respectively. Three weeks before H1, the subjects underwent one control experiment in normoxia (N; inspired oxygen fraction 20.9%) without any treatment. Serum alpha-tocopherol was significantly higher after treatment with antioxidants compared with placebo. Capillary Po(2) declined during H without significant differences between antioxidants and placebo. Plasma peroxide levels were lower under antioxidant treatment but not affected by hypoxia. The response of Epo to H did not show significant differences between antioxidant [maximum increase (means, 95% confidence interval): +121%, +66 to +176%] and placebo conditions (+108%, +68 to +149%). Similarly, hypoxia-induced increase of Epo corrected for diurnal variations, as revealed during N, did not differ between antioxidants and placebo. Individual variability of Epo in response to H was not related to the individual degree of hypoxemia during H. Our results do not support the assumption that ROS play a major modulating role in the response of Epo to short-term normobaric hypoxia in humans.

Antioxidants↗

[Individual radioresistance and principles of its formation].

Individual variability of resistance to a broad range of ionizing radiation was analyzed. Individual radioresistance depends both on physical (radiation type, dose, and distribution along the body, dose rate) and biological (species, strain, sex, body mass of animal etc.) factors. Individual radioresistance is manifested by specific and nonspecific responses of organism to radiation. Three components of individual radioresistance are stable, semistable and labile. The stable component is genetically determined by species, sex, habitus status and radiosensitivity of cells of critical organs. The semistable component is determined by embryogenetic, early postnatal development and reflected in functional activity of the main regulatory systems of the body. The labile component is a parameter of current functional state of an indviduum. The stable and semistable components characterize inborn whereas the labile component--acquired radioresistance.

Animals↗

[Quantified research of measuring postural balance by posturography using inclinometer technique].

OBJECTIVE: To gain the normal values of posturography using inclinometer technique in people, to gain the normal values of posturography using inclinometer technique in people. METHOD: The messages of postural average sway angular velocity (omega) obtained by posturography using inclinometer technique in four various conditions were measured in 167 normal subjects who were grouped by age. RESULT: The normal omega values show that there is no correlation between postural balance with gender, but postural balance is related with age. The postural stability is at its best at the age of 20 to 60 years. The direction of postural sway has a large inter-individual variability, but no significant inclined direction is found. CONCLUSION: The results of individual tests should be compared with match-aged normative data in order to determine abnormal postural balance function. We measured many subjects and grouped by ages in detail. Therefore, the result can be taken as normative data of the measuring system. The omega value of standing on global-ottomed platform with eye closed could distinguish abnormal balance function of vestibo-spinal system accurately.

Adult↗

Temporal and intrapopulation variation in prey choice of wintering geese determined by stable isotope analysis.

1. Individual variability in prey preferences can have marked effects on many demographic parameters from individual survival and fecundity to the vital rates of entire populations. A population level response is ultimately determined by individual prey choices; however, the effect of individual dietary choice is often overlooked. 2. We determined prey choice by individual consumers, light-bellied Brent geese Branta bernicla, during the overwintering period. Two hundred and eighty-one individuals were sampled at distinct temporal points over two winters. Stable isotopic ratios of carbon and nitrogen for blood cells and blood plasma, from each sampled individual were measured. Isotopic ratios for potential prey items were also measured. 3. Delta15N and delta13C for blood samples were both significantly different between sample months. Generally we found a decrease in both isotopic ratios during the course of the winter. All potential prey items were also isotopically distinct. Multisource mixing models (isosource) were used to determine the range of possible contribution to the diet of individuals. 4. During early winter, diet consisted almost exclusively of sea grass Zostera spp. The level of Zostera spp. in the diet dropped until mid-winter, and was supplemented by the utilization of green algae Ulva lactuca, and Enteromorpha spp., and terrestrial grasses. Terrestrial grass comprised an increasing proportion of the diet in late winter, representing virtually the exclusive food source by April. 5. By examining intrapopulation variability in resource utilization we highlight a number of ecologically important factors not addressed by previous population level studies.

Animals↗