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PubMed2001

Three-dimensional kinematics of the lumbar spine during treadmill walking at different speeds.

The lumbar spine is of primary importance in gait and its development is influenced by the upright posture adopted in human locomotion. However, little is known about the kinematic behavior of the lumbar spine during walking. The aim of this study was to examine (1) lumbar spine kinematics during walking, (2) the effect of walking velocity on lumbar motion patterns and (3) the coupling characteristics of rotation and bending. In 22 volunteers aged 15-57 years, the three-dimensional displacements of T12 to the sacrum were sampled during elementary movements of the trunk and during walking on a treadmill at four walking velocities. A three-dimensional electrogoniometer (CA 6000 Spine Motion Analyzer) sampling at 100 Hz was used. We analyzed maximal primary and coupled motion ranges (ROM) and velocities in each plane. Lumbar ROM during walking did not exceed 40% of maximal active ROM. Transverse plane ROM and frontal and transverse velocities increased with walking velocity. Coupling of rotation and bending during walking was individually variable and dependent on walking velocity. Moreover, the smoothness of the bending-rotation path varied with walking velocity. A simplified envelope of lumbar coupling characteristics during walking is presented, and the existence of an individually variable walking speed that is characterized by a more harmonic lumbar contribution is hypothesized.

Adult↗
PubMed1976

Effects of transcendental meditation on fine motor skill.

46 college female volunteers were given 66 10-sec. trials on the pursuit rotor task in 3 practice sessions (18, 30, and 18 trials/sessions). After the first 18 trials, the 23 subjects who were practiced Transcendental Meditators mediated for a 20-min. period followed by a 5-min. "waking" phase prior to the performance of a further 30 trials on the rotor. A 4-min. rest was taken before resuming practice for the final 18 trials. The other 23 subjects, who were not meditators, followed the same procedures except instead of mediating they sat quietly with closed eyes. In terms of performance, learning, reminiscence and intra-individual variability, the two groups were similar. These results were not in accordance with the expectations that these parameters would reflect the facilitative effects of Transcendental Meditation on alertness, awareness, consistency, and resistance to stress. After the meditation session, inter-individual variability was increased for the mediation group. While the conclusion that the practice of Transcendental Meditation does not benefit acquisition of fine perceptual-motor skill appears strong, further investigation would assist in obtaining a more complete understanding of such effects on perceptual-motor behavior.

Female↗
PubMed2005

Resistance to abomasal nematodes and individual genetic variability in reindeer.

Resistance to parasites is believed to have a widespread influence on demographic and adaptive processes. In systems where parasites impose a fitness cost on their host, heterozygotes may be selected because they are more resistant to parasites than homozygotes. Our objective was to assess the relationships between genomewide individual heterozygosity and abomasal nematode burdens in female Svalbard reindeer (Rangifer tarandus platyrhynchus) after the effects of host age, locality, season, and year had been accounted for. Samples were obtained from 306 female reindeer that were culled and genotyped at nine microsatellite loci. Reindeer in our study populations are mainly parasitized by the gastrointestinal nematodes Ostertagia gruehneri and Marshallagia marshalli. The infection intensity of each parasite differed between subpopulations, and among host age classes, seasons and years. We found no significant relationships between abomasal worm burdens, or lumen and mucosa larvae, of either O. gruehneri or M. marshalli and individual heterozygosity (or mean d(2)) alone or in interactions with host age, locality, and year. Although we analysed one of the largest data set available to date on gastrointestinal nematodes of a wild ruminant, we used a typical data set of nine genetic neutral markers that may have had low power to detect heterozygosity-fitness correlations. We conclude that the proportion of the variance in parasite resistance explained by individual heterozygosity for neutral genetic markers is low in Svalbard reindeer and in vertebrates in general, and we suggest that the candidate-gene approach might be more fruitful for further research on gene-fitness correlations.

Abomasum↗
PubMed2004

Cyclosporin A pharmacokinetics and efficacy in the treatment of atopic dermatitis in dogs.

A series of experiments was conducted to study cyclosporin A (CsA) pharmacokinetics in dogs and the factors influencing variability of blood concentrations. In a first study, influence of feeding on drug absorption and blood profile was evaluated. Administration of CsA as micro-emulsion (ME) formulation with food decreased the bioavailability by 22% and increased the individual variability of drug absorption. In a second study, pharmacokinetic profiles from laboratory fasted beagle dogs receiving orally CsA ME formulation were analyzed. CsA was measured in blood samples by high-performance liquid chromatography (HPLC, 34 profiles) and fluorescent polarization immunoassay (FPIA, 16 profiles). A two-compartment model with first-order absorption was used to calculate the pharmacokinetic parameters. Using FPIA, blood concentrations were 1.5 to 1.7 times higher than when using HPLC, but elimination half-life and MRT were similar. The coefficient of variation of key pharmacokinetic parameters ranged from 27 to 34% following HPLC assay. The same range of variation was obtained after FPIA assay. In a third study, in a clinical trial evaluating CsA for the treatment of canine atopic dermatitis, a single blood sample was collected in dogs which had received CsA for 28 days. No significant correlation was found between clinical improvement and CsA blood concentrations. Considering the large margin of safety of CsA in dogs, the limited inter-individual variability and the lack of correlation between blood concentrations and clinical response, routine monitoring of blood CsA does not appear necessary in dogs with atopic dermatitis.

Administration, Oral↗
PubMed1992

Variability in response to a low-fat, low-cholesterol diet in children with elevated low-density lipoprotein cholesterol levels.

The reduction of dietary cholesterol and fat lowers low-density lipoprotein cholesterol (LDL-C) and reduces risk of coronary heart disease in adults. The purpose of this study was to determine the individual variability of response of serum lipid and lipoprotein levels to a low-fat, low-cholesterol diet in children with elevated LDL-C levels. Thirty-two children (2 to 16 years of age) enrolled in a diet modification program, who had LDL-C levels of at least 110 mg/dL but normal triglyceride levels for their ages, were studied. Lipid levels and dietary nutrients were analyzed at the time of admission, and final assessments were made at least 3 months after entry. There was a significant correlation, for the group as a whole, between change in LDL-C concentration and change in grams of dietary saturated fat; however, there was marked individual variability in LDL-C response. There were no significant correlations between changes in LDL-C levels and changes in either total fat, polyunsaturated fat, or cholesterol intake. It is concluded that modest decreases in dietary saturated fat coincide with a lowering of LDL-C concentration, over a short term, in many children, but the degree of lowering varies considerably from one child to another. This variability is consistent with the concept that response of serum lipid levels to dietary changes is modified by genetic, metabolic, and other, as of yet, undefined variables.

Child↗
PubMed1990

Morphology and development of the terminal portion of the abdominal aorta in cow during fetal and neonatal periods.

Analysis of morphological and developmental features of arteries forming the terminal portion of the aorta was performed. These are the external iliac, umbilical, median sacral, ovarian, caudal mesenteric and lumbar arteries. In the earliest fetuses slow rate of development of the branches of aorta is stated. However, beginning from 13th week ot gestation the rate increases causing considerable developmental and individual variability of the vessels. At the end of the fetal period and in newborns a decrease in the rate of the development of the terminal portion of the aorta is typical for the species and sex except individual variability of its secondary branches.

Animals↗
PubMed1996

Acute sensitivity vs. context-specific sensitization to cocaine as a function of genotype.

Individual variability in the acute and chronic effects of psychomotor stimulants is due, in part, to genetic factors. The purpose of this series of studies was to utilize a behavioral model of sensitization, namely increased locomotor activity, to assess individual variability in sensitization to the chronic effects of cocaine and its relationship to the acute stimulant effects of cocaine. Because the degree of sensitization is proportional to the training dose, genetic differences in acute sensitivity to cocaine were assessed and incorporated into the sensitization paradigm. Acute sensitivity and context-dependent sensitization were determined in six inbred mouse strains. Large quantitative and qualitative differences were found in the acute potency and efficacy of cocaine to stimulate locomotor activity. The ED50 was higher in the strains in which cocaine was most efficacious. Context-specific sensitization was determined via chronic administration of equiactive doses of cocaine (ED50) specifically paired with the test apparatus or with the home colony. Sensitization was time, environment, and genotype dependent. The differences in the number of trials required to show sensitization were unrelated to the acute locomotor stimulant effects of cocaine. These findings suggest that acute cocaine-induced locomotor activity and context-specific sensitization reflect different pharmacological properties of cocaine.

Animals↗
PubMed2006

Poor correlation between 6beta-hydroxycortisol:cortisol molar ratios and midazolam clearance as measure of hepatic CYP3A activity.

AIMS: A non-invasive proposed method for measuring CYP3A activity is the urinary 6beta-hydroxycortisol:cortisol ratio. This ratio has been used as an indicator of CYP3A induction and inhibition, with mixed results. This investigation evaluated the relationship between a validated, biomarker, intravenous midazolam clearance and the urinary cortisol ratio under constitutive conditions and with the influence of a moderate CYP3A inhibitor. METHODS: This was a sequential, cross-over study design. Intravenous midazolam 0.025 mg kg(-1) was administered to 10 male and 10 female subjects once every 14 days for 4 months. Fluvoxamine 150 mg day(-1) was given to all subjects during the last two visits. Total body clearance of midazolam and urinary 6beta-hydroxycortisol:cortisol molar ratio were used as biomarkers of hepatic CYP3A activity. RESULTS: No significant correlations were found between these two markers (r(2) < 0.5, P > 0.05). Larger interindividual and intra-individual variability in CYP3A activity was observed in 6beta-hydroxycortisol:cortisol ratios compared with midazolam clearances. With fluvoxamine therapy, midazolam clearance values decreased approximately 1.5-fold and cortisol ratios decreased approximately 1.9-fold. CONCLUSIONS: The high intra-individual variability of the urinary cortisol ratio, compared with midazolam, makes this a suboptimal CYP3A phenotyping tool.

Adult↗
PubMed1997

Digital-image analysis of the rhomboid fossa surface.

Forty brainstems were investigated in order to evaluate morphological and morphometrical variability of the 4th ventricle floor. Visibility evaluation of the following rhomboid fossa structures: striae medullares, facial colliculus, superior fovea, vestibular area, sulcus limitans, incisure, medial eminence, median sulcus, vagal triangle, hypoglossal triangle and obex was performed. Obex, median sulcus, vestibular area, vagal and hypoglossal triangles were found to be sufficiently visible in all specimens. Facial colliculus was poorly visible in 37% of the examined brainstems. Striae medullares were invisible in 30% of the analysed material and exhibited individual variability of a high degree in relation to their number and arrangement. Morphometrical study showed measured distances to be individually variable with a relatively low coefficient of variation of approximately 10%.

Adult↗
PubMed1981

Thresholds for the perception of rotation: variability, psychometric curves, and comparison with hearing thresholds.

Psychometric curves were determined for the perception of rotation about a vertical axis. If a logarithmic scale is used, an integrated Gaussian curve gives a reasonable description of the psychometric curve. This curve is characterized by two values: the 50% point, which is defined as the threshold, and the s.d. The s.d. of the vestibular psychometric curve is about 10 dB which is 4 times larger than the s.d. found for the auditory system. The distribution of vestibular thresholds in healthy subjects obtained by Clark and Stewart (1969) is plotted on a logarithmic acceleration scale; it can fitted by a Gaussian function. The s.d. of this function is 5.5 dB, a value which is similar to that found for auditory thresholds. From this it is concluded that the inter-individual variability of the detection threshold for the vestibular system is the same as the inter-individual variability of the detection for the auditory system.

Acoustic Stimulation↗
PubMed1999

Leptin concentration in newborns' cord blood: relationship to gender and growth-regulating hormones.

AIMS: To verify if plasma leptin concentrations of newborns at birth differ significantly between sexes; and to investigate the potential interactions between plasma leptin and growth-regulating hormones at birth. SUBJECTS: 98 healthy newborns (48 male, 50 female) were studied. Leptin, insulin, cortisol, insulin-like growth factor-1 (IGF-1), testosterone, and sex hormone binding globulin (SHBG) concentrations were measured from venous blood collected from the umbilical cord vein immediately after birth. RESULTS: The serum leptin concentration of newborns averaged 8.05(0.5) ng/ml. Females had significantly (P<0.005) higher serum leptin values than males [9. 6(0.8) vs 6.0(0.6) ng/ml]. IGF-1 was significantly (P<0.05) higher in females than in males [87(4) vs 74(5) microg/l], whereas SHBG was slightly lower [29(1) vs 33(2) nmol/l]. Insulin, cortisol, and testosterone serum concentrations were not statistically different between the sexes. Among the variables examined, birth weight (expressed as Z-score of weight) and insulin showed the highest degree of relationship with serum leptin in newborns (r=0.48 and r=0.31 respectively, P<0.001). Multiple regression analysis showed that Z-score of birth weight, gender and cortisol were able to account for approximately 44% of inter-individual variability of serum leptin concentrations in newborns. CONCLUSIONS: Female newborns have significantly higher serum leptin concentrations than males. Insulin, IGF-1, testosterone, and SHBG did not independently affect leptin inter-individual variability when gender, Z-score of body weight, and cortisol were taken into account. Other factors may be involved in the differences in circulating leptin concentrations between the sexes in newborns.

Female↗
PubMed2001

The predictive value of MDR1, CYP2C9, and CYP2C19 polymorphisms for phenytoin plasma levels.

Phenytoin, an anticonvulsant, exhibits nonlinear pharmacokinetics with large interindividual differences. Because of its small therapeutic range with the risk of therapeutic failure or adverse drug effects in susceptible persons, therapeutic drug monitoring is frequently applied. The interindividual differences in dose response can partially be explained by known genetic polymorphisms in the metabolic enzyme CYP2C9 but a large deal of individual variability remains still unexplained. Part of this variability might be accounted for by variable uptake of phenytoin, which is a substrate of p-glycoprotein, encoded by the human MDR1 gene. We evaluated, whether phenytoin plasma levels correlate with a polymorphism in the MDR1 gene, C3435T, which is associated with intestinal PGP activity. Genotyping and analyses of plasma levels of phenytoin and metabolites in 96 healthy Turkish volunteers showed that the MDR1C > T3435 polymorphism affects phenytoin plasma levels (P = 0.064) and the metabolic ratio of p-HPPH vs phenytoin (MDR1*TT genotype, P = 0.026). The MDR1*CC genotype is more common in volunteers with low phenytoin levels (P < or = 0.001, chi2 test). A combined analysis of variable alleles of CYP2C9, 2C19 and MDR1 revealed that the number of mutant CYP2C9 alleles is a major determinant, the number of MDR1*T alleles further contributes to the prediction of phenytoin plasma levels and CYP2C19*2 does not explain individual variability. The regression equation that fitted the data best included the number of mutant CYP2C9 and MDR*T alleles as predictory variables and explained 15.4% of the variability of phenytoin data (r2 = 0.154, P = 0.0002). Furthermore, analysis of CYP2C9 and MDR1 genotypes in 35 phenytoin-treated patients recruited from therapeutic drug monitoring showed that combined CYP2C9 and MDR1 analysis has some predictive value not only in the controlled settings of a clinical trial, but also in the daily clinical practice.

Adolescent↗
PubMed1999

Night-time quiescence and morning activation in the human colon: effect on transit of dispersed and large single unit formulations.

OBJECTIVES: Controlling the delivery of drugs to different regions of the colon remains an elusive goal. The aim of this study was to define the diurnal variation in colonic transit and show how this influences the colonic distribution and residence time of different formulations given either in the morning or evening. METHODS: Colonic transit of small particulates and a large capsule was measured during nocturnal sleep and daytime wakefulness. Eighteen healthy volunteers participated in a randomised crossover study. 111In-labelled resin (150-300 microm) and a large 99mTc-labelled non-disintegrating capsule (22 x 8 mm) were swallowed at either 0800h or 1700h. MAIN OUTCOME MEASURES: The geometric centre of isotope (range 1-9) was calculated from serial scintiscans allowing comparison of overnight and daytime transit. RESULTS: Transit of resin was delayed in the overnight compared to daytime 8 h periods (change in geometric centres (GCs), mean +/- SEM, 0.59 +/- 0.14 vs 1.46 +/- 0.39 respectively, P < 0.02). Maximal resin movement occurred immediately after awakening, prior to breakfast, in 9/18 studies (P < 0.05). The capsule was more distal than the resin at the end of the study 15 h after dosing (P < 0.001). There was marked inter-individual variability in distribution of both resin and capsule at 15 h, the range of GCs being 2.8-9 and 2.2-9, respectively. CONCLUSION: Sleep delays colonic transit and large capsules travel faster than dispersed small particles. However, substantial inter-individual variability in transit makes targeting specific regions of the human colon unreliable with either dispersed or single unit formulations.

Administration, Rectal↗
PubMed1997

Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes.

Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism. The chromium requirement is postulated to increase with increased glucose intolerance and diabetes. The objective of this study was to test the hypothesis that the elevated intake of supplemental chromium is involved in the control of type 2 diabetes. Individuals being treated for type 2 diabetes (180 men and women) were divided randomly into three groups and supplemented with: 1) placebo, 2) 1.92 micromol (100 microg) Cr as chromium picolinate two times per day, or 3) 9.6 micromol (500 microg) Cr two times per day. Subjects continued to take their normal medications and were instructed not to change their normal eating and living habits. HbA1c values improved significantly after 2 months in the group receiving 19.2 pmol (1,000 microg) Cr per day and was lower in both chromium groups after 4 months (placebo, 8.5 +/- 0.2%; 3.85 micromol Cr, 7.5 +/- 0.2%; 19.2 micromol Cr, 6.6 +/- 0.1%). Fasting glucose was lower in the 19.2-micromol group after 2 and 4 months (4-month values: placebo, 8.8 +/- 0.3 mmol/l; 19.2 micromol Cr, 7.1 +/- 0.2 mmol/l). Two-hour glucose values were also significantly lower for the subjects consuming 19.2 micromol supplemental Cr after both 2 and 4 months (4-month values: placebo, 12.3 +/- 0.4 mmo/l; 19.2 micromol Cr, 10.5 +/- 0.2 mmol/l). Fasting and 2-h insulin values decreased significantly in both groups receiving supplemental chromium after 2 and 4 months. Plasma total cholesterol also decreased after 4 months in the subjects receiving 19.2 micromol/day Cr. These data demonstrate that supplemental chromium had significant beneficial effects on HbA1c, glucose, insulin, and cholesterol variables in subjects with type 2 diabetes. The beneficial effects of chromium in individuals with diabetes were observed at levels higher than the upper limit of the Estimated Safe and Adequate Daily Dietary Intake.

Adult↗
PubMed2002

A new accelerometric method to assess the daily walking practice.

OBJECTIVE: To describe a method to obtain a profile of the duration and intensity (speed) of walking periods over 24 hours in women under free-living conditions. DESIGN: A new method based on accelerometry was designed for analyzing walking activity. In order to take into account inter-individual variability of acceleration, an individual calibration process was used. Different experiments were performed to highlight the variability of acceleration vs walking speed relationship, to analyze the speed prediction accuracy of the method, and to test the assessment of walking distance and duration over 24-h. SUBJECTS: Twenty-eight women were studied (mean+/-s.d.) age: 39.3+/-8.9 y; body mass: 79.7+/-11.1 kg; body height: 162.9+/-5.4 cm; and body mass index (BMI) 30.0+/-3.8 kg/m(2). RESULTS: Accelerometer output was significantly correlated with speed during treadmill walking (r=0.95, P<0.01), and short unconstrained walks (r=0.86, P<0.01), although with a large inter-individual variation of the regression parameters. By using individual calibration, it was possible to predict walking speed on a standard urban circuit (predicted vs measured r=0.93, P<0.01, s.e.e.=0.51 km/h). In the free-living experiment, women spent on average 79.9+/-36.0 (range: 31.7-168.2) min/day in displacement activities, from which discontinuous short walking activities represented about 2/3 and continuous ones 1/3. Total walking distance averaged 2.1+/-1.2 (range: 0.4-4.7) km/day. It was performed at an average speed of 5.0+/-0.5 (range: 4.1-6.0) km/h. CONCLUSION: An accelerometer measuring the anteroposterior acceleration of the body can estimate walking speed together with the pattern, intensity and duration of daily walking activity.

Acceleration↗
PubMed1992

Drug-testing in patients with pulmonary hypertension of unknown cause.

The acute haemodynamic effects of seven different drugs were serially evaluated in eight patients suffering from pulmonary hypertension of unknown cause. The following drugs were tested in randomized order: nifedipine, amrinone, isoproterenol, captopril, prostacyclin, dihydralazine and nitroglycerin. Only a reduction in pulmonary vascular resistance (PVR) of more than 30% of baseline was considered a satisfactory response. Overall, the decrease in PVR ranged from 9 +/- 12% (nitroglycerin) to 38 +/- 23% (prostacyclin). However, marked inter- and intra-individual variability in the efficacy of all drugs was observed, making cross reactivity totally unpredictable. The number of responders for each drug varied between five (prostacyclin) and zero (dihydralazine, nitroglycerin). Conversely, a maximum of three drugs was capable of eliciting a response in an individual patient, with only two out of eight patients being total non-responders. A reduction in PVR of more than 30% (n = 16) was associated with a significant decrease in mean pulmonary artery pressure (49.1 +/- 8.2 versus 39.4 +/- 6.4 mmHg) and a significant increase in cardiac index (2.5 +/- 0.6 versus 3.4 +/- 0.8l.min-1.m-2). Overall, none of the drugs tested proved to be clearly superior. However, because of marked inter- and intra-individual variability, the therapeutic approach must be based on trial and error and the evaluation of all drugs is indicated if one fails.

Adult↗
PubMed1995

The psychopharmacological basis of nicotine's differential effects on behavior: individual subject variability in the rat.

Nicotine, the presumed active pharmacological agent in tobacco, produces variable effects on behavior that are at best described as "paradoxical" in nature. Thus, nicotine, via tobacco use in humans or nicotine administration in experimental animals, tends to transpose behavior depending on predrug baseline rates of behavior. High rates of behavior appear to be reduced, while low rates of behavior appear to be increased by nicotine. This work further proposes that nicotine's variable effects on behavior may be related to its capacity to act as a behavioral agonist and/or antagonist via its ability either to activate or to desensitize distinct central nicotinic acetylcholinergic receptors (nAChR's). Nicotine is portrayed as a neuronal modulating agent that can affect behavior contingent upon the genetic makeup of the individual subject being studied. Depending on the structure, function, and location of distinct nAChR's, nicotine appears to be able to induce a wide range of behavioral effects important to the tobacco user. However, this does not rule out the role the importance that other biogenic amine systems (i.e., serotonin or dopamine) may have in the genetics of tobacco use or nicotine's variable effects on behavior.

Acetylcholine↗
PubMed2004

The bispectral index does not correlate with clinical signs of inhalational anesthesia during sevoflurane induction and arousal in children.

PURPOSE: Validation of the bispectral index (BIS) in children requires correlating BIS with several levels of sedation, hypnosis and anesthesia. Our purpose was to compare BIS values with objective assessments of the level of hypnosis in children. We postulated that BIS predicted the level of anesthesia during induction and emergence in children. METHODS: In a prospective observational study, we evaluated the BIS monitor in 87 children (ages: 0.3 to 14 yr) ASA physical status I-II undergoing general surgery under sevoflurane and nitrous oxide. Clinical signs of inhalational anesthesia (CSA), the motor response to surgical incision and signs of arousal were used as indicators of the depth of anesthesia. CSA and BIS measurements were paired every minute during induction and emergence until arousal. RESULTS: CSA scores decreased during induction and increased during emergence (P < 0.001) and correlated with changes in sevoflurane concentrations (r = -0.46; P < 0.001). BIS was associated with changes in CSA scores during induction (r = 0.49; P < 0.01) and emergence (r = 0.62; P < 0.01), but the ranges of individual BIS values overlapped several levels of hypnosis. A BIS value greater than 50 had a positive predictive value of 25% for distinguishing between responders and non-responders to surgical incision. A BIS score equal or greater than 72 had a predictive value of 63% for discriminating between pre-arousal and arousal. CONCLUSIONS: BIS correlates with several levels of hypnosis during inhalational induction and emergence in children, but individual BIS values show large inter-individual variability. The BIS monitor identified the physiological changes associated with arousal and distinguished the effects of preoperative sedation during emergence. The use of movement as an endpoint of hypnosis during surgical stimulation does not correlate with BIS values in children. The large inter-individual variability of BIS at different levels of anesthetic depth may limit the applicability of BIS to pediatric anesthesia.

Adolescent↗