Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Individual variability”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed1976

[Investigations on the Variability of the phasic pupillary light reflex (author's transl)].

Infrared pupillography was used to determine physiological time parameters of the direct phasic light reflex in 101 normal subjects. These parameters include latency, contraction and redilatation times as well as total reaction time, measured in response to 4 different light stimulus intensities. A total of more than 4000 pupillary stimulations in these subjects was analyzed statistically. The study of these time parameters included determination of the mean, the standard deviation and three dimensional analysis of variance, with the following results: 1. The physiological time parameters are bilaterally symmetrical. 2. The most stable parameters with least variability in an individual subject were latency and contraction time. The redilatation time, however, showed marked intra-individual variability. 3. Variance analysis revealed a high degree of correlation among the different parameters to light stimuli of varying intensity. 4. There was a highly significant prolongation of latency and of contraction time with increasing age. 5. No sex dependent effect on physiological time parameters was found. In addition, no interaction among light stimulus intensity, age and sex could be detected. Possible applications of the method for clinical neurological examination are discussed.

Adolescent↗
PubMed2003

Population pharmacokinetics of gentamicin in South African newborns.

OBJECTIVE: Gentamicin population pharmacokinetics in newborns were studied with special reference to possible gender effects. METHODS: Steady-state serum levels ( n=139) were obtained from 79 neonates with a mean birth weight of 2.1 kg, mean gestational age of 35.1 weeks and mean age at the time of sampling of 4.2 days. The data were analysed using the non-linear mixed effects model (NONMEM). A one-compartment model was used to fit the data. RESULTS: The final models for clearance (CL) and volume of distribution (V) were: CL(l/h)=0.001xWGTxGAxP and V(l)=0.472xWGT, where WGT=birth weight (kg), GA=gestational age (weeks) and P=1.2 for girls and 1.0 for boys. The values of inter-individual variability in CL and V were 34% and 35%, respectively. Intra-individual variability was 5% (proportional) and 7.2% (additive). Mean (95% confidence interval) values of CL and half-life were 0.042 l h(-1) kg(-1) (0.041, 0.043 l h(-1) kg(-1)) and 8.0 h (7.7, 8.3 h), while V was 0.472 (0.428, 0.516) l/kg for all patients. CONCLUSION: Mean population pharmacokinetic values were similar to those obtained with NONMEM for gentamicin in other neonates of similar age. Gender was found to be a determinant of CL, with girls clearing faster than boys.

Anti-Bacterial Agents↗
PubMed1998

Determination of population pharmacokinetic parameters for amikacin in neonates using mixed-effect models.

OBJECTIVE: The population pharmacokinetics of amikacin, in neonates, was investigated using the nonlinear mixed effects model (NONMEM). METHODS: One hundred and six steady-state amikacin serum levels were obtained from 53 black neonates with a mean gestational age of 35.1 weeks and mean age at the start of treatment of 3.1 days. A one-compartment model was used to fit the data. RESULTS: The final models for clearance (CL) and volume of distribution (V) were: CL(l.h(-1)) = 0.031WT(1.45) x P and V(l) = 0.316WT(1.44) where WT = birth weight (kg) and P = 1.28 for girls and 1.0 for boys. Inclusion of other fixed effect parameters in the model did not significantly improve the fit of the data. The inter-individual variability for CL and V were 18% and 13%. respectively. Intra-individual variability was 29%. Mean (95% CI) values of CL, V and half-life were 0.048 (0.045, 0.051) l.h(-1).kg(-1), 0.434 (0.414, 0.453) l.kg(-1) and 6.4 (6.2, 6.6) h respectively. CONCLUSION: Birth weight was an important determinant of both CL and V and, in this data set, gender was also found to influence CL. Mean population pharmacokinetic values were within the range of those previously derived for other neonatal populations using traditional methods.

Amikacin↗
PubMed1985

The mortality predictive power of discharge electrocardiogram after first acute myocardial infarction.

The prognostic value of discharge ECG was studied in 457 patients after their first acute myocardial infarction. Thirteen different ECG variables were studied on the discharge ECG. When cumulative 4-year survival rates were calculated by standard life-table method for each variable individually, the following variables had statistically significant prognostic power: PTF (P terminal force), PTFA (P terminal frontal axis), AF (atrial fibrillation), ST depression, ST elevation, QRS duration, and the combination block (LBBB/RBBB + LAHB/LPHB). The variables with no statistically significant predictive power were: QTc, LBBB or RBBB, LAHB or LPHB, AV block, T wave angle, T negativity, and sigma R. The relative risks for the most important variables in the discrete life-table model were: PTF 3.4, QRS duration 3.3, ST depression 2.6, PTFA 2.5, and ST elevation 2.2. In further analysis a model with only three ECG variables (PTF, ST depression, and ST elevation) was developed which stratified the study population in categories with 1.9% to 75.5% estimated 4-year survival rates.

Adult↗
PubMed1990

Molluscicidal trials and correlation between the presence of Tetrapleura tetraptera in an area and the absence of the intermediate hosts of schistosomiasis and fascioliasis in southwest Nigeria.

A schistosomiasis research project, carried out in Southwest Nigeria, yielded data by which it was possible to relate snail recovery from potential transmission sites to the presence or absence of Tetrapleura tetraptera. A significant negative correlation with snail numbers was found for distance of T. tetraptera from transmission sites and fruiting of the trees when these variables were tested individually. There were no significant differences between individual variables such as pH, Ca2+ concentrations and temperatures for these snail habitats but these variables produced significant positive correlation with the number of snails recovered. Thus, the presence of T. tetraptera appeared to be the most important limiting factor for the presence of snails. Aqueous extracts of T. tetraptera were effective as a molluscicide against Bulinus globosus and Lymnaea natalensis. However, pollution of the environment by oils reduced or abolished the molluscicidal activity of T. tetraptera. The results indicate that the planting of T. tetraptera has potential for the local control of schistosomiasis.

Animals↗
PubMed2004

Discriminant function sexing of fragmentary femur of South African blacks.

When fragmentary and incomplete bones are all that are available to the forensic anthropologist for use in sex determination, non-metric and metric sex discriminating parameters that have been derived from complete bones may be of little use. In such circumstances, sex discriminating metric methods that are of specific application to fragmentary bones will be more useful. Since such studies have not been systematically carried out in bones of South African blacks, the aim of this study was to begin to provide such data. Two hundred and twenty left femurs of black South Africans were obtained from the Raymond A. Dart Collection of African Skeleton, School of Anatomical Sciences, University of the Witwatersrand, South Africa. Five variables from the upper end of the femur and three variables from the lower end of the femur were measured and subjected to univariate and multivariate discriminant function analyses. The vertical head diameter and the medial condylar length were most successful in sex identification from the upper and lower ends of the femur respectively. The combined variables were more useful than the use of variables individually. Discriminant function score equations were derived for individual and combined variables from the upper and lower ends of the femur of the South African blacks.

Anthropometry↗
PubMed2001

Applications of population approaches in toxicology.

Many experimental or observational studies in toxicology are best analysed in a population framework. Recent examples include investigations of the extent and origin of intra-individual variability in toxicity studies, incorporation of genotypic information to address intra-individual variability, optimal design of experiments, and extension of toxicokinetic modelling to the analysis of biomarker studies. Bayesian statistics provide powerful numerical methods for fitting population models, particularly when complex mechanistic models are involved. Challenges and limitations to the use of population models, in terms of basic structure, computational burden, ease of implementation and data accessibility, are identified and discussed.

Animals↗
PubMed2004

Evaluating differences between measured personal exposures to volatile organic compounds and concentrations in outdoor and indoor air.

Accurate estimation of human exposures to volatile organic compounds (VOCs) is a key element of strategies designed to protect public health from the adverse effects of hazardous air pollutants. The focus here is on examining the capability of three different exposure metrics (outdoor community concentrations, indoor residential concentrations, and a simple time-weighted model) to estimate observed personal exposures to 14 VOCs. The analysis is based on 2-day average concentrations of individual VOCs measured concurrently in outdoor (O) air in three urban neighborhoods, indoor (I) air in participant's residences, and personal (P) air near the breathing zone of 71 healthy, nonsmoking adults. A median of four matched P-I-O samples was collected for each study participant in Minneapolis/St. Paul over three seasons (spring, summer, and fall) in 1999 using charcoal-based passive air samplers (3M model 3500 organic vapor monitors). Results show a clear pattern for the 14 VOCs, with P > I > O concentrations. Intra-individual variability typically spanned at least an order of magnitude, and inter-individual variability spanned 2 or more orders of magnitude for each of the 14 VOCs. Although both O and I concentrations generally underestimated personal exposures, I concentrations provided a substantially better estimate of measured P concentrations. Mean squared error (MSE) as well as correlation measures were used to assess estimator performance at the subject-specific level, and hierarchical, mixed effects models were used to estimate the bias and variance components of MSE by tertile of personal exposure. Bias and variance both tended to increase in the upper third of the P exposure distribution for O versus P and I versus P. A simple time-weighted model incorporating measured concentrations in both outdoor community air and indoor residential air provided no improvement over I concentration alone for the estimation of P exposure.

Air Pollutants↗
PubMed1994

Comparative dosimetry of O6-methylguanine in humans and rodents treated with procarbazine.

The accumulation of O6-methylguanine (O6-meG) in the DNA of blood leukocytes of 21 Hodgkin's lymphoma patients (followed for up to 12 cycles of treatment) treated in the context of MOPP combination chemotherapy with 150 mg procarbazine daily for 10 days was examined and compared to that observed in rats treated with different doses of procarbazine as a single agent once per day for 10 days. In humans, the adduct accumulated in a dose-related fashion and appeared to approach a steady-state after 7-8 days of treatment. Adduct levels on day 10 of the treatment cycle averaged 0.25 +/- 0.09 (mean +/- SD) mumol/molG and, for different individuals, covered a 3-fold range. Intra-individual variability between different treatment cycles was much more limited than inter-individual variability, the two parameters accounting for 8.9% and 84.5% respectively of adduct variance at a constant cumulative dose. Comparison of the dose-response relationships for humans and rats indicates that, under conditions of no depletion of O6-alkylguanine-DNA alkyltransferase (AGT), O6-meG accumulates in blood leukocyte DNA of humans at a rate which is only approximately 2-fold lower than in rats, implying that, to the extent to which O6-meG contributes to the genotoxic activity of procarbazine, human susceptibility to it is likely to be comparable to that of the rat. This is likely to be true also of the bone marrow (the tissue of interest as a target tissue for leukaemogenesis), since the tissue distribution of O6-meG induced by low doses of procarbazine in rats, mice and rabbits indicated that blood leukocyte levels of this adduct closely reflect those in the bone marrow. Based on these results, it is estimated that by the end of a MOPP chemotherapy cycle O6-meG reaches levels of the order of 0.2-0.3 fmol/microgram DNA (0.3-0.5 mumol/molG) in human bone marrow (the target tissue of leukaemogenesis observed after such treatment).

Animals↗
PubMed1990

Chlorination, water hardness and serum cholesterol in forty-six Wisconsin communities.

The Wisconsin Heart Health Research Program measured serum lipids and other clinical parameters among residents of 46 neighbouring small communities in central Wisconsin. The purpose of the study was to determine whether distribution of serum lipids, blood pressure or thyroid hormones differed according to the chlorination of water supply, or to its calcium and magnesium content (hardness). This report examines serum lipid levels in relation to the drinking water characteristics chlorination and hardness. Variables measured on individuals included age, education level, alcohol intake, cigarette smoking, dietary fat and dietary calcium. An analysis of covariance was used to estimate effects of chlorination and hardness on each of the serum lipids, with individual variables included as covariates. Among females, serum cholesterol (SC) levels are significantly higher in chlorinated communities than in non-chlorinated communities. Community SC levels are also higher for males in chlorinated communities, on the average, but differences are smaller and not statistically significant. Low density lipoprotein (LDL) cholesterol levels follow a similar pattern to that for total SC levels, higher in chlorinated communities for females, but not different for males. On the other hand, high density lipoprotein (HDL) cholesterol community means are nearly identical in the chlorinated and non-chlorinated communities for each sex.

Adult↗
PubMed2007

Radiation-induced micronucleus frequencies in female peripheral blood lymphocytes collected during the first and second half of the menstrual cycle.

Biological dosimetry relies on the assessment of dose in peripheral blood lymphocytes (PBL) of a victim. Variability in the individual radiosensitivity of PBL has an impact on the precision of dose estimate and radiation-induced micronuclei show a strong individual variability. A factor which can influence the radiosensitivity of PBL is the hormonal status of female donors, which shows a regular pattern during the menstrual cycle. The aim of the present investigation was to verify whether the position within the menstrual cycle has an impact on the level of micronuclei in PBL. Blood was collected from 19 donors during the first and second half of the menstrual cycle and exposed to 2 Gy. Although statistically significant differences between the MN frequencies in PBL collected during the different time points were observed in the case of some donors, no reproducible trend that could find application in biological dosimetry could be detected.

Adult↗
PubMed1987

Longitudinal study of pulmonary function development in childhood, adolescence, and early adulthood. Development of pulmonary function.

The growth of pulmonary function between 5.5 and 25 yr of age was determined using 1,511 observations over time on 353 subjects from a representative population sample of white non-Mexican-Americans in Tucson. There was an average of 8.8 yr of follow-up, with a maximum of 12. The method used was shown to be robust for span of follow-up from 3 to 12 yr (3 to 7 observations), and the results were verified by standard statistical methods. The standard error of the estimate decreased linearly with follow-up, indicating the need for longitudinal evaluation. Respiratory symptoms and diagnoses had the biggest negative impact on growth of lung function, using FVC, FEV1, Vmax50, and size-compensated flows (Vmax50/FVC). Smoking had the next biggest negative impact. Smoking cessation was shown to have a positive impact on growth of pulmonary function. Using a second linear model to adjust for individual variability and the random variability over surveys, individual growth showed similar trends. Further negative impacts were due to parental smoking, especially as it interacts with active smoking and respiratory disease. Flows at end of follow-up (Vmax50, Vmax50/FVC) were more sensitive than FEV1 to the effects of concurrent disease and smoking, and more persistent effects of these factors in early adulthood.

Adolescent↗
PubMed1994

Effects of Valsalva's manoeuvre on intraocular pressure.

We examined the effects of breath holding against a closed glottis (Valsalva's manoeuvre) on intraocular pressure (IOP) in four groups of volunteer subjects: 37 healthy young control subjects, 10 patients with chronic open-angle glaucoma, 11 age-matched control subjects and 8 glaucoma suspects. IOP was recorded by one person using a Digilab 30R/T Pneuma-Tonometer. Chart recordings of the IOP were measured independently by a second investigator. Recordings were taken before, during and 5 minutes after the seated subject exhaled into an aneroid manometer to a pressure of 25 to 35 cm H2O. There was marked variability in the individual responses to Valsalva's manoeuvre in all four groups, with substantial increases (to +9.5 mm Hg) and decreases (to -4.0 mm Hg) in IOP seen. The mean change in IOP during Valsalva's manoeuvre was a small, statistically insignificant decrease in all four groups. The mean change in IOP following Valsalva's manoeuvre was a larger, but still clinically small, decrease. The clinician should be aware of the individual variability in IOP changes with Valsalva's manoeuvre.

Adult↗
PubMed1995

Pharmacokinetics, safety and tolerability of the orally administered receptor antagonist of cysteinyl-leukotrienes BAY x 7195 in single-dose escalation studies.

BAY x 7195 is a novel receptor antagonist of cysteinyl-leukotrienes currently under development for the treatment of asthma. It is effective in antagonizing the leukotriene-D4 induced bronchoconstriction in healthy volunteers following oral administration. The pharmacokinetics, safety and tolerability of the drug were investigated in six partially placebo-controlled studies in healthy volunteers with single oral administration of a 50, 100, 250, 500 and 1000 mg dose as a tablet. The drug was well tolerated. The only remarkable adverse event was diarrhea in one volunteer receiving the highest dose of 1000 mg. There were no additional clinically relevant changes in any safety parameter including laboratory values. Concentrations of BAY x 7195 were determined in plasma and urine by high performance liquid chromatography with fluorescence detection and plasma-concentrations were further evaluated by compartmental and non-compartmental methods. The concentration vs time profiles of the drug were biphasic with a dominant t1/2 of 0.5-2 h and a terminal t1/2 of 5-10 h. Pharmacokinetics were linear in the investigated range of doses. In spite of substantial inter-subject variability intra-individual variability in AUC and Cmax was reasonable. In general, the concentration vs time profiles could be described with a 2-compartment body model. However, in some cases the occurrence of second and third concentration maxima necessitated the use of a multiple segment absorption model to accomplish a good fit to the data. Enterohepatic recirculation following glucuronidation of the drug is the likely reason for the multiple peaks. Urinary excretion of BAY x 7195 and its glucuronide metabolite was negligible the amount excreted into urine from 0 to 48 h being < 0.1% of the dose. The low renal clearance of BAY x 7195 (< or = 0.07 ml/min) is suggestive of significant reabsorption in the renal tubuli taking into account that the expected renal clearance for a drug with 99.5% protein binding is about 0.6 ml/min.

Administration, Oral↗
PubMed1987

Variable threshold of exertional ischaemia in patients with positive exercise test at low workload.

In order to determine individual variability of ischaemic threshold on different days, 18 patients with exertional ischaemia at low workload were studied. All patients performed two exercise tests during different days in the morning and three on the same day at 9 am, 2 pm and 5 pm. The test performed in the morning on different days resulted in a significant difference in the mean values of rate pressure product at the ischaemic threshold as a consequence of individual variability observed in 10 patients. In 8 of these patients the differences were greater than 4000 mmHg beats min-1. Two patients showed respectively, 1 and 5 negative exercise tests despite the greater values of rate pressure product reached. Only 3 patients showed circadian variation of the ischaemic threshold; in these 3 patients variations of rate pressure product at the ischaemic threshold were also observed between different days. These data indicate that in patients with exertional ischaemia at low workload the rate pressure product at the ischaemic threshold shows considerable variability between tests performed on different days.

Angina Pectoris↗
PubMed1992

Stability and variability in hormonal responses to prolonged exercise.

To study the dynamics of alterations in blood hormones and their individual variability during prolonged exercise, changes in plasma levels of corticotropin, cortisol, aldosterone, testosterone, progesterone, somatotropin, insulin and C-peptide were recorded in 32 endurance athletes and 50 untrained persons during a 2-hour exercise on a cycle ergometer at 60% VO2max. Common changes were activation of the pituitary corticotropin function, mostly at the end of exercise, rises in aldosterone and somatotropin concentrations and decreases in insulin and C-peptide levels during exercise. The activation of pituitary-adrenocortical system and the decrease of insulin but not C-peptide levels were more pronounced in athletes than in untrained persons. A large inter-individual variability existed in changes of cortisol, testosterone and progesterone in both groups. Five variants were found in the dynamics of cortisol concentration. Whereas the alterations of corticotropin were characterized mainly by a biphasic increase, the dynamics of corticotropin and cortisol coincided only in one variant out of five. Most characteristic for the postexercise recovery period were decreased activity of the pituitary-adrenocortical system and delayed normalization of aldosterone level.

Adolescent↗
PubMed2002

In silico prediction of optimal in vivo delivery properties using convolution-based model and clinical trial simulation.

PURPOSE: To develop a new strategy for the in silico evaluation of the optimal in vivo delivery properties of a drug, minimizing a cost function defined by the brain receptor occupancy obtained in positron-emission tomography experiments. METHODS: A convolution-based model was formulated to link in vivo delivery rate to plasma concentrations whereas a second-stage model was used to link plasma concentrations to the pharmacodynamic effect. A feedback control approach was applied to identify the optimal in vivo delivery rate given an appropriate optimality criterion. Finally, clinical trial simulation was used as a supportive tool for decision-making by evaluating different scenarios accounting for pharmacokinetic/pharmacodynamic parameter uncertainty, inter-subject variability. and drug potency. RESULTS: The results revealed that the mean in vivo delivery time significantly affects brain receptor occupancy whereas the fraction of the dose available for the systemic circulation shows the highest influence on brain receptor occupancy for a given in vivo delivery rate. Finally, variability on receptor occupancy seems to be more affected by the inter-individual variability on the disposition PK parameters. CONCLUSION: The integration of convolution-based model. feedback control approach, and clinical trial simulation offers a unique tool for in ilico improvement of the drug development process by identifying critical issues on drug properties, optimal in vivo delivery rate, and potential problems related to the inter-individual variability.

Clinical Trials as Topic↗
PubMed2006

Dose-response of altitude training: how much altitude is enough?

Altitude training continues to be a key adjunctive aid for the training of competitive athletes throughout the world. Over the past decade, evidence has accumulated from many groups of investigators that the "living high--training low" approach to altitude training provides the most robust and reliable performance enhancements. The success of this strategy depends on two key features: 1) living high enough, for enough hours per day, for a long enough period of time, to initiate and sustain an erythropoietic effect of high altitude; and 2) training low enough to allow maximal quality of high intensity workouts, requiring high rates of sustained oxidative flux. Because of the relatively limited access to environments where such a strategy can be practically applied, numerous devices have been developed to "bring the mountain to the athlete," which has raised the key issue of the appropriate "dose" of altitude required to stimulate an acclimatization response and performance enhancement. These include devices using molecular sieve technology to provide a normobaric hypoxic living or sleeping environment, approaches using very high altitudes (5,500m) for shorter periods of time during the day, and "intermittent hypoxic training" involving breathing very hypoxic gas mixtures for alternating 5 minutes periods over the course of 60-90 minutes. Unfortunately, objective testing of the strategies employing short term (less than 4 hours) normobaric or hypobaric hypoxia has failed to demonstrate an advantage of these techniques. Moreover individual variability of the response to even the best of living high--training low strategies has been great, and the mechanisms behind this variability remain obscure. Future research efforts will need to focus on defining the optimal dosing strategy for these devices, and determining the underlying mechanisms of the individual variability so as to enable the individualized "prescription" of altitude exposure to optimize the performance of each athlete.

Acclimatization↗