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PubMed2005

Individual variability in cardiovascular disease risk factor responses to low-fat and low-saturated-fat diets in men: body mass index, adiposity, and insulin resistance predict changes in LDL cholesterol.

BACKGROUND: Although reductions in total and saturated fat consumption are recommended to reduce the risk of cardiovascular disease, individual variability in plasma lipid responses exists. OBJECTIVE: Our aim was to determine the effect of adiposity and insulin resistance on the lipoprotein response to diets lower in total and saturated fat than the average American diet (AAD). DESIGN: A randomized, double-blind, 3-period crossover controlled feeding design was used to examine the effects on plasma lipids of 3 diets that differed in total fat: the AAD [designed to contain 38% fat and 14% saturated fatty acids (SFAs)], the Step I diet (30% fat with 9% SFAs), and the Step II diet (25% fat with 6% SFAs). The diets were fed for 6 wk each to 86 free-living, healthy men aged 22-64 y at levels designed to maintain weight. RESULTS: Compared with the AAD, the Step I and Step II diets lowered LDL cholesterol by 6.8% and 11.7%, lowered HDL cholesterol by 7.5% and 11.2%, and raised triacylglycerols by 14.3% and 16.2%, respectively. The Step II diet response showed significant positive correlations between changes in both LDL cholesterol and the ratio of total to HDL cholesterol and baseline percentage body fat, body mass index, and insulin. These associations were largely due to smaller reductions in LDL cholesterol with increasing percentage body fat, body mass index, or insulin concentrations. Subdivision of the study population showed that the participants in the upper one-half of fasting insulin concentrations averaged only 57% of the reduction in LDL cholesterol with the Step II diet of the participants in the lower half. CONCLUSION: Persons who are insulin resistant respond less favorably to Step II diets than do those who are insulin sensitive.

Adipose Tissue↗
PubMed1993

Carbonyl (phenone) reductase in human liver: inter-individual variability.

The enzyme family carbonyl reductase, which catalyses the reduction of xenobiotic as well as endogenous ketones and aldehydes, has not been very well studied in terms of its biological functions and structural aspects. The aim of the present study was to check for the occurrence of inter-individual variability of carbonyl reductase activity in human liver. In vitro metabolism of p-nitroacetophenone (PNAP, a prototype substrate) indicated the presence of a high- and low-affinity enzyme site. The reductase activity of 17 kidney donor livers was screened at two concentrations (0.05 and 0.5 mM PNAP, below and above Km). The rates of reductase activity at 0.05 mM suggested a normal distribution. In contrast, at 0.5 mM the rates indicated a non-normal distribution, i.e. bi- or tri-modality. As an index of variability of enzyme affinity, ratios of velocities at 0.5 to 0.05 mM PNAP were calculated in order to check their frequency distributions. Three out of 17 kidney donor livers showed an atypical ratio. In these three cases, the high ratio was due to the low activity of the high affinity form of carbonyl reductase. Autopsy livers are a more readily available tissue source and about half the activity of the kidney donor livers was found in 43 autopsy livers indicating that they are a useful source of human tissue for studies of carbonyl reductase.

Acetophenones↗
PubMed2006

Age and individual variability in performance during sleep restriction.

The effect of sleep loss on reaction time (RT) performance varies as a function of age, with RTs of older subjects typically showing less decrement (relative to rested baseline) than those of younger subjects. In the current paper, we examined the nature of this relationship in a 7-day sleep restriction study. The number of repeated measures made it possible to model both intra-individual trajectories over days and individual differences in these trajectories. Results revealed (a) consistent individual differences in RT patterns over time after controlling for experimental design effects; (b) less cumulative RT decline among older individuals regardless of the degree of sleep restriction; and (c) consistent individual variability in performance patterns even after accounting for the effects of age.

Adult↗
PubMed2000

Effect of tourniquet pressure and intra-individual variability on plasma fibrinogen, platelet P-selectin and monocyte tissue factor.

Small differences in levels of certain haemostatic components may be clinically significant. It is important therefore to eliminate potential sources of confounding variability. This study investigated the effect of removing tourniquet pressure prior to sample collection on plasma fibrinogen levels, platelet P-selectin and monocyte tissue factor expression. Blood was collected from the right arm under maintained tourniquet pressure and from the left arm following the release of pressure once the vein was sufficiently inflated for insertion of a needle. Whole blood was labelled within one hour of venepuncture to allow analysis of platelet P-selectin and monocyte tissue factor by flow cytometry. Plasma fibrinogen levels were analysed in samples stored at -70 degrees C, for all individuals at the end of the study using a method based on the Clauss technique. Intra-individual variability for each of the components was assessed by collecting samples under tourniquet pressure from four individuals on the same day on three consecutive weeks. Intra-individual variations were greater than assay CVs for all three components. There were no significant differences between the two tourniquet methods of collection for fibrinogen, P-selectin or tissue factor. In conclusion, there is no reason not to use a tourniquet during collection of blood for analysis of plasma fibrinogen, platelet P-selectin or monocyte tissue factor.

Adolescent↗
PubMed2005

Inter- and intra-individual variability in transdermal fentanyl absorption in cancer pain patients.

A transdermal therapeutic system (TTS) is recommended for use in chronic cancer pain, particularly in the advanced stages. The aim of this trial was to study intra- and interindividual variabilities in fentanyl transdermal absorption and investigate physiological and clinical parameters that can influence the absorption in patients treated using a TTS for moderate to severe cancer pain. The study group consisted of 108 patients (71 men and 37 women; mean age, 61.3 years) with chronic cancer pain. A total of 507 patches were analysed. The TTSs used to administer fentanyl were removed after a 72-h period. The amount of fentanyl remaining in the patches was determined using a high-performance liquid chromatography method with ultraviolet detection. Depending on the analgesic requirements of the patient, the dose of fentanyl administered by TTS ranged from 25 to 500 microg/h. The study period was 6 months. Large interindividual variability in the amount of remaining fentanyl in the patches occurred. For 58.1% of patches, absorption was 60 to 84%; for 33.2% of them, it was lower; and for 8.8%, it was higher than this range. The intra-individual variability ranged from 2.8 to 75.1%. The bioavailability of fentanyl was statistically different according to patient age. Patients >75 years of age absorbed 50% of the fentanyl during the selected 72-h period, whereas patients <65 years absorbed 66%. Moreover, there is a significant difference in the percentage of absorbed fentanyl according to the type of cancer. The absorption was higher in patients with breast or digestive cancer than in those with lung cancer. Hyperhidrosis, hypertrichosis and the localization of patches on the skin did not influence bioavailability. For the entire group, transdermal fentanyl treatment provided good to excellent pain relief in the majority of patients.

Administration, Cutaneous↗
PubMed1994

The micronucleus assay in human lymphocytes: screening for inter-individual variability and application to biomonitoring.

Micronuclei levels were assessed in cytokinesis-blocked lymphocytes of 200 male and female healthy donors not occupationally exposed to genotoxic risks and of 33 male industrial painters handling genotoxic substances. Frequency of micronucleated cells was 9.87 +/- 3.1 per 1000 in the control population and was shown to have a large inter-individual variability. The study of factors contributing to this variability showed that only smoking could affect micronucleated cell rate, inducing an increase of 25%, whereas age and sex had no effect. Among the industrial painters, frequency of micronucleated cells averaged 18.30 +/- 7.39 per 1000: the difference between the two populations studied was shown to be statistically significant by the Mann-Whitney rank sum test (one-sided U test) and indicated that exposed painters need preventive measures.

Adult↗
PubMed1983

Prognosis in equine colic: a study of individual variables used in case assessment.

The individual merit of the use of 43 variables to assess the prognosis of equine colic cases was examined. The following variables revealed highly significant (P less than 0.001) differences between cases which survived and those which died: blood pressure; heart rate; oral mucosal capillary refill time; degree of mental depression; venous haemoglobin concentration, haematocrit, erythrocyte count, urea concentration and lactate concentration; peritoneal fluid lactate concentration; and haematocrit/plasma protein and serum protein concentration ratios. Thus, in general, variables which assessed cardiovascular function were good prognostic guides.

Animals↗
PubMed1993

Thermogenic response to food: intra-individual variability and measurement reliability.

The objective of this study was to assess the reliability and variability of the thermogenic response to food (TRF) in healthy adult subjects. Eight healthy adults (4 men, 4 women) participated in three sets of measurements of TRF, evaluated by indirect calorimetry with a ventilated hood system during 6 hours after a standardized meal. The reliability of TRF measurement was estimated using a one-way analysis of variance with repeated measurements. After the 6-hour period of measurement, the within-subject coefficient of variation for TRF was 10.7%, while the between-subject variability was twice as high (24.1%, p < 0.01). The overall reliability estimate of TRF was acceptable (RE > or = 0.80) after a single measurement which lasted at least 6 hours postprandially, while duplicate and triplicate measurements reached a similar degree of reliability in 3 hours. These results suggest that intra-individual variability contributes little to the variability commonly seen in TRF studies, provided that the measurement period is at least 6 hours.

Adult↗
PubMed1992

Individual variability in the response to different opioids: report of five cases.

Although it is widely appreciated that patients can demonstrate highly variable responses to different opioid drugs, there have been few detailed descriptions of this phenomenon. To illustrate this variability, we present 5 patients, 4 with cancer pain and 1 with non-malignant pain, who underwent dose titration with more than 1 opioid and developed markedly different responses to each. In every case, dose escalation led to successful treatment with 1 opioid and to intolerable side effects without adequate relief with others. The existence of this individual variability in the response to different opioids has important implications for both clinical practice and current understanding of opioid pharmacology in man. It contradicts the view that any opioid is inherently more efficacious than any other, suggests that patients who fail to obtain adequate pain relief at maximally tolerated doses of 1 opioid may benefit from an alternative drug, and underscores the potential importance of genetic factors as a determinant of opioid response.

Adult↗
PubMed1984

The visual field representation in striate cortex of the macaque monkey: asymmetries, anisotropies, and individual variability.

The topographic organization of striate cortex in the macaque was studied using physiological recording techniques. Results were displayed on two-dimensional maps of the cortex, which facilitated the quantitative analysis of various features of the visual representation. The representation was found to be asymmetric with more cortex devoted to lower than to upper fields. Over much of striate cortex the representation is anisotropic, in that the magnification factor depends upon the direction along which it is measured. There is considerable individual variability in these features as well as in the overall size of striate cortex. Outside the fovea, the cortical representation shows only modest deviations from a logarithmic conformal mapping, in which the magnification factor is proportional to the inverse of eccentricity in the visual field. Comparison of receptive field size with cortical magnification was used to estimate the "point image size" in the cortex (i.e. the extent of cortex concerned with processing inputs from any given point in the visual field). Our evidence supports a previous report that point-image size varies significantly with eccentricity. This is of interest in relation to anatomical evidence that the dimensions of columnar systems in striate cortex are largely independent of eccentricity.

Animals↗
PubMed2006

Individually variable energy management strategies in relation to energetic costs of egg production.

Marked interindividual variation in metabolic rate suggests considerable complexity in energy management strategies, but attempts to further our understanding of the relationship between resting metabolic rate (RMR), daily energy expenditure (DEE), and reproductive effort have been hampered by the complexity of studying this system in the field. Here, we describe energy management strategies in a captive-breeding system, using Zebra Finches (Taeniopygia guttata), to demonstrate the high level of complexity and interindividual variability in energy expenditure, food intake, locomotor activity, and reproductive effort. In particular, we investigated whether the increase in RMR associated with egg production is additive, resulting in higher DEE and a need for elevated food intake, or whether this cost is compensated by reduced expenditure in nonreproductive components of the energy budget. We found high levels of intra-individual variation in energy expenditure associated with egg production in female Zebra Finches, e.g., comparing nonbreeding stage with the one-egg stage, change in RMR varied from 4.0% and 41.3%, and change in DEE varied from -33.3% to +46.4%. This variation was systematically related to aspects of locomotor activity and reproductive effort. Females with the largest increase in RMR during egg production decreased locomotor activity the most but still had increased DEE at the one-egg stage, and females with high DEE at the one-egg stage produced larger clutches. Our study suggests that females minimize increases in DEE during egg production through behavioral energy reallocation (reduced locomotor activity) but that individuals differ in their use of this strategy, which, in turn, is related to the absolute level of reproductive investment. This suggests a very complex, individually variable system of energy management to meet the demands of egg production.

Animals↗
PubMed1993

Skin barrier function in healthy volunteers as assessed by transepidermal water loss and vascular response to hexyl nicotinate: intra- and inter-individual variability.

This study assesses the variability of two non-invasive methods of measuring stratum corneum barrier function in vivo. Transepidermal water loss (TEWL), and the vascular response to hexyl nicotinate (HN) penetration as determined by laser-Doppler flowmetry, were measured in a group of 21 healthy volunteers. Each time profile of the vascular response to HN penetration was analysed using the following parameters: the baseline cutaneous blood flow, the lag-time between application and initial response (t0), the time between application and maximum response (tmax), the maximum response, and the slope of the curve. TEWL measured on the left volar forearm showed a normal range of 3.9-7.6 g/m2h and a small inter-individual variability [coefficient of variation (CV) 19.4%]. TEWL values at three other forearm sites did not show differences of clinical importance compared with the left volar forearm. The parameters of the vascular response to HN penetration spanned a wider normal range than the TEWL values (CV between 33 and 52%). Repeat measurements after a 1-2 month interval showed highly reproducible individual TEWL values. The mean difference between first and second measurements was only 0.03 g/m2h; the relative difference 0.6%. The intra-individual reproducibility of t0 and tmax. for HN penetration was also high (relative differences of 2.8 and 3.1%, respectively). The other vascular response parameters were less reproducible (relative differences of 6.9-18.6%). We conclude that TEWL and selected parameters of HN penetration, as non-invasive tests of the stratum corneum barrier function, yield reproducible results and are hence useful for investigations assessing the skin barrier function in various disorders.

Adolescent↗
PubMed1991

Individual variability in concentrations of urinary sulindac sulfide.

Among 70 patients with arthritis who were receiving satisfactory maintenance therapy with sulindac (300 to 400 mg daily), 64% had no detectable sulindac sulfide (active metabolite) in one to four random urine specimens. However, 36% had 1.0 to 7.8 (mean, 2.2 +/- 1.4) micrograms/ml sulindac sulfide in urine, similar to the therapeutically effective concentrations found in 24 concurrent plasma specimens (1.4 to 9.0 micrograms/ml). Ten patients had sulindac sulfide in only one or two of two to four urine specimens. Thus, 36% of the patients had pharmacodynamically significant concentrations of sulindac sulfide in urine, presumably capable of suppressing the cyclooxygenase pathway responsible for prostaglandin synthesis in the kidney and elsewhere. The findings suggest individual variability in the capacity for renal oxidation of sulindac sulfide to inactive metabolites, perhaps related to genetic or environmental factors or both. These findings may help to explain conflicting reports on the effects of sulindac on urinary prostaglandins and renal function.

Adult↗
PubMed2006

Individual variability, end-point effects and possible biases in electrophysiological research.

Neocortical dynamics and signals reflect spatiotemporal cortical synchronization as well as functional condition and modulation by subcortical projecting structures that determine the brain state. However, neurotransmitters interact and neuronal function and signals also reflect non-neuronal factors that should (but not necessarily are, or can) be taken into proper consideration in neuroscience. Examples in this regard are the CNS modulation by spontaneous or induced changes in metabolism (e.g. glucose, ammonia), blood flow, pO(2), pCO(2), hormones (thyroxine; sexual hormones, ATCH) and neurohormonal interaction, maturation, aging, temperature, light-dark regulation of serotonine, histamine and dopamine/melatonin/vitamin B12 secretion and interaction, etc. Hormones also regulate the (functional) maturation and differentiation between sexes both during development and in adult life. These factors interact with each other and individually or collectively can account for unexplained or underestimated individual variability; on occasions, may become critical variables in animal or human research. In specific instances, variability is the information of interest. However, physiological variability due to neuronal or non-neuronal factors can interact with the experimental setups or affect electrophysiological signals to extents that can result in biased findings in otherwise controlled studies. An "inverse problem" difficult to approach may ensue in both animal and human research; in several instances, the specificity of brain signals for the investigated function may require experimental validation.

Analgesia↗
PubMed1994

Inter and intra-individual variability of sperm morphology after selection with three different techniques: layering, swimup from pellet and percoll.

Sperm morphology has been suggested to be one of the most reliable factor in predicting male fertility potential both in spontaneous cycles and in assisted reproduction. In this work the morphology of spermatozoa selected with three different techniques (layering, swimup from pellet and mini-percoll) has been assessed and compared in 20 infertile patients. All the techniques allowed the recovery of sperm populations of a better quality than in basal samples, with a higher percentage of normal forms (p < 0.001). No significant differences were observed among the three different techniques in selecting sperm populations. The scatter diagrams comparing pairwise differences between the methods against their means regard the percentage of normal forms selected show a great (over 20%) inter and intra-individual variability. These data demonstrate that the three techniques select different percentages of normal spermatozoa, even in the same patient. Since it is crucial to obtain the highest number of morphologically normal and motile spermatozoa and each technique may provide different results in a given patient, we suggest that at least two techniques of sperm selection be performed before assisted reproduction procedures. This combined testing could also be relevant in the prognostic evaluation of the infertile male, since it explores the different characteristics of sperm function.

Adult↗
PubMed2006

Marked individual variability in the levels of trimethylselenonium ion in human urine determined by HPLC/ICPMS and HPLC/vapor generation/ICPMS.

Selenium species were determined using HPLC/ICPMS and HPLC/vapor generation/ICPMS in the urine from seven human volunteers investigated at background selenium concentrations and at slightly elevated concentrations after ingestion of 200 microg Se as a selenite supplement. Trimethylselenonium ion (TMSe) was present, together with selenosugars, in the urine samples, a result that dispels recent doubts about its possible previous misidentification with a cationic selenosugar. Although TMSe was present as only a trace metabolite in urine from five of the seven volunteers (0.02-0.28 microg Se/L, equivalent to 1-5% of the sum of selenosugars and TMSe), it was a significant metabolite (up to 4.6 microg Se/L, 22%) in one volunteer, and it was the major identified metabolite (up to 15 microg Se/L, 53%) in another volunteer. This marked individual variability in the formation of TMSe was maintained in a duplicate investigation of urine from the same seven volunteers.

Adult↗
PubMed1993

Inter-individual variability in the dynamics of natural accommodation in humans: relation to age and refractive errors.

1. To study the relationship between accommodation under natural viewing conditions, age and refractive errors, we have measured time courses of accommodation in thirty-nine human subjects aged 5-49 years using a newly developed technique. The technique is based on infrared photoretinoscopy and involves fully automated on-line image processing of digitized video images of the eyes with a sampling rate of 5.3 Hz. 2. The distance between the subject and the video camera was about 1.3 m. Head movements of the subject required little restriction because the eyes were automatically tracked in the video image by the computer program. All subjects were tested under binocular viewing conditions. 3. Both refraction of the right eye and pupil diameter were measured with a precision of 0.2-0.4 dioptres (D) and 0.1 mm, respectively, and were plotted on-line. The data were subsequently automatically analysed. 4. Automated infrared photoretinoscopy proved to be very convenient and easy to handle in both children and adults. 5. The maximal speed of accommodation for a target at a distance of 5 D declined in the subjects with age (from up to 21.7 D s-1 for accommodation and 32.7 D s-1 for subsequent accommodation to a distant target ('near to far accommodation') in children down to 2-18 D s-1 in adults). There was a striking inter-individual variability in the maximum possible speed of accommodation and near to far accommodation. 6. Speed of accommodation and of near to far accommodation was correlated for each subject. However, in most of the subjects, the process of near to far accommodation was faster than accommodation (P < 0.005, if averaged over all subjects). This correlation was independent of age. 7. The accommodation-induced pupillary constriction (pupillary near response) was absent in children for a 4 D target; even at 10 D, there was no reliable pupillary response. The pupillary near response increased to about 1.6 mm D-1 of accommodation at the age of 47. Since a pupillary near response could still be elicited in presbyopic subjects unable to accommodate, the ratio of pupillary constriction per dioptre of accommodation approached infinity. 8. The magnitude of the pupillary near response was highly variable even among subjects of the same age but was typical for each subject. There was a correlation (P < 0.01) to refractive error: corrected myopes had weaker pupillary near responses than emmetropes or hyperopes.(ABSTRACT TRUNCATED AT 400 WORDS)

Accommodation, Ocular↗
PubMed1992

Cortisol metabolism by human liver in vitro--I. Metabolite identification and inter-individual variability.

The measurement of urinary 6 beta-hydroxycortisol (6 beta-OHF) has been widely used as a non-invasive clinical test to detect cytochrome P450 induction. Although only a minor biotransformation, 6 beta-OHF formation represents a sensitive target for many P450-inducing drugs and environmental chemicals in man. There is good evidence that an isozyme of the P450IIIA subfamily is predominantly responsible for 6 beta-hydroxylase activity and therefore it has been suggested that urinary 6 beta-OHF is a marker of the induction of P450IIIA. The basis of the present study was that in order to realistically assign to 6 beta-OHF the status of a P450IIIA marker we should characterize all the metabolites of cortisol produced by human liver and assess inter-liver variability. Incubations at 37 degrees C for 2 h contained [3H]cortisol (0.1 microCi, 1 or 50 microM), MgCl2 (10 mM), microsomal or cytosolic protein (3 mg), an NADPH-regenerating system and 1/15 M phosphate buffer (pH 7.4) to give a final volume of 0.5 ml. Extraction with ethyl acetate (2 x 2 ml) was followed by radiometric HPLC analysis. Metabolites were identified by co-chromatography with authentic standards and mass spectrometry (electron impact and chemical ionization). All the microsomal incubations (n = 6 livers) produced 6 alpha-hydroxycortisol (6 alpha-OHF), 6 beta-OHF, 20 beta-dihydroxycortisol, 20 beta-dihydroxycortisone, cortisone, and 3 alpha, 5 beta-tetrahydrocortisone (3 alpha, 5 beta-THE), while five produced 6 beta-hydroxycortisone and four produced 3 alpha, 5 beta-tetrahydrocortisol (3 alpha, 5 beta-THF). The cytosolic incubations gave a much simpler metabolic profile, with 3 alpha, 5 beta-THF the major metabolite and 3 alpha, 5 beta-THE a minor metabolite. There was considerable inter-individual variability in metabolite profiles from microsomal incubations. 6 beta-OHF varied from 2.8 to 31.7%. Major metabolites were cortisone and 3 alpha, 5 beta-THE. Inter-liver variability was less for cytosolic incubations, the major metabolite always being 3 alpha, 5 beta-THF. In conclusion we have rigorously identified the hepatic metabolites of cortisol formed in vitro. The highly complex and variable hepatic metabolism of cortisol clearly limits the use of urinary 6 beta-OHF excretion as a marker of baseline P450IIIA activity in man.

Adolescent↗