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PubMedDate not supplied

Contributing factors and variability of energy expenditure in non-obese, obese, and post-obese adolescents.

Energy expenditure (EE) is a major determinant of energy balance and body composition. The objectives of this paper were to review the contributing factors of the main components of daily EE (DEE) and the inter-individual variability in these components in non-obese (NOb), obese (Ob), and post-obese (POb) adolescents. Body composition especially fat-free mass (FFM), is the major determinant of the basal metabolic rate which contributes 50-70% of DEE, whereas fat mass (FM) is a significant factor only in obese subjects. Physical activity is the second main variation factor of DEE, whereas growth, the thermic effect of food, and thermoregulation are generally of marginal importance. The energy costs and EE associated with various sedentary and physical activities were assessed in NOb, Ob and POb subjects both in standardised and in free-living conditions. The interindividual variability of DEE is high, even after adjustment for body composition, mainly because of great differences in time devoted to the various physical activities. DEE and EE associated with sleep and sedentary activities are significantly higher in Ob than in NOb, but not after adjustment for FFM. On the contrary, EE associated with physical activities is not significantly different between Ob and NOb adolescents, but 61% lower in Ob subjects after adjustment for body composition. Multidisciplinary weight-reduction programmes including moderate energy restriction and physical training result in great FM loss, maintenance of FFM, improvement of physical capacities, but reductions in organ and tissue metabolic rate and in EE associated with the various sedentary and physical activities, which may favour body weight regain in the less active POb subjects.

Adolescent↗
PubMed2006

The psychological and physiological responses of sedentary individuals to prescribed and preferred intensity exercise.

OBJECTIVES: Affective valence responses to exercise may influence adherence. According to a newly proposed dual-mode model, affective responses have been proposed to vary depending on whether exercise is undertaken above or below the anaerobic threshold. With the model in mind, the study objectives were to explore the impact of an above-lactate, below-lactate, and self-selected exercise condition on acute affective responses in sedentary individuals. DESIGN: Using a repeated measures design, 12 volunteers participated in two prescribed intensity exercise conditions (above and below-lactate threshold) and one self-selected intensity exercise condition. The three conditions were randomized. METHOD: An incremental walking protocol was used to identify exercise intensities that would elicit above- and below-lactate threshold work rates for each participant. The exercise conditions were completed on different days and each lasted for 20 minutes. Physiological and affective responses were recorded pre-exercise, during exercise, and post-exercise. RESULTS: Affective responses were more negative in the above-lactate condition during exercise compared with the below-lactate and self-selected conditions. There were no differences between the conditions post-exercise. Participants exercised around the lactate threshold and at a significantly higher intensity in the self-selected compared with the below-lactate condition. Inter-individual variability in responses was greatest below the lactate threshold, with similar levels of variability in the self-selected and above-lactate conditions. CONCLUSIONS: Data are consistent with the proposals of the dual-mode model and support the use of self-selected intensity with sedentary individuals to promote positive affective responses.

Adult↗
PubMed2003

Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers.

Cigarette smoking is the major risk factor for developing chronic bronchitis, yet only 15-20% of smokers develop this disorder. Because oxidants are the major mechanism of smoking-induced airway damage, we hypothesized that smoking is associated with upregulation of various antioxidant-related genes in the airway epithelium, but the magnitude of the response shows high inter-individual variability. Microarray analysis was used to assess levels of expression of 44 antioxidant-related genes in four categories (catalase/superoxide dismutase family; glutathione metabolism; redox balance; and pentose phosphate cycle) in bronchoscopy-obtained airway epithelium of matched cohorts (13 current smokers, 9 nonsmokers), none of whom had lung disease. There was minimal variation in gene expression levels within the same individual (right versus left lung or over time), but significant upregulation of 16/44 antioxidant-related genes in smoker epithelium compared with nonsmokers. Subgroups of smokers were identified with clusters of expression levels of antioxidant-related genes. We propose that the antioxidant-related genes demonstrating the most variability in the level of expression in smokers may be useful genetic markers in epidemiologic studies assessing susceptibility to smoking-induced chronic bronchitis.

Adult↗
PubMed1993

Population pharmacokinetics of theophylline. II: Intravenous infusion to patients with stable chronic airway obstruction.

The population pharmacokinetics of theophylline were studied in 55 patients with stable chronic airway obstruction. Two hundred and seventy six theophylline serum concentrations after intravenous short infusion were analyzed using a nonlinear mixed-effect model. The influence of hepatic dysfunction, smoking habit, age and the measurement of arterial blood gases (oxygen tension: PaO2, carbon dioxide tension: PaCO2, blood pH) and clinical laboratory tests (serum albumin concentration, haematocrit) on the pharmacokinetic parameters of theophylline was examined by the likelihood ratio test. Assessment of each factor was made by a forward selection method. In the final regression model, the total body clearance (CL, l/h/kg) was related to the value of PaCO2 as well as to the presence of hepatic dysfunction, and the volume of distribution (Vd, l/kg) was related with the PaCO2 value as expressed in the following equations: CL = exp(-3.78 - 0.525.HF + 0.0233.PaCO2) and Vd = exp(-1.12 + 0.00934.PaCO2), where HF is a categorical variable with a value of unity if a patient has hepatic dysfunction otherwise zero. The interactions among blood gas measurements were observed and the CL and Vd of theophylline would be inversely correlated with PaO2 or pH, if we selected PaO2 or blood pH to be a more important factor than PaCO2. The inter-individual variabilities in CL and Vd were 38.5% and 12.5%, respectively, and the residual variability in theophylline serum concentrations was 10.6% as a coefficient of variation. This final model and the population parameters of theophylline will be useful for individualization of a drug dosage regimen by means of the Bayesian method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

[Acupuncture and bronchial asthma].

The 66 randomized patients with mild bronchial asthma who took part in this study were divided into three nearly equal groups. Group one was treated with true acupuncture during the first and the fourth month (up to week 16). Group two was treated similarly but needled at non-acupuncture points. The third group served as a control. All patients were allowed to maintain their normal asthma medication with the recommendation to keep the regimen unchanged until week 20, i. e. 4 weeks after termination of the specific treatment. The changes in peak flow variability up to week 16 served as main outcome criterion. Additional parameters included several spirometric analyses as well as various markers in blood and sputum that are specific for the allergic inflammatory reaction of the upper respiratory tract. The values measured showed considerable individual variability. This impeded the demonstration of efficacy. In conclusion it can be stated that there was a consistent, positive yet unspecified effect of the needling in both treated groups which can be interpreted as a trend in affecting the asthmatic condition. This effect could have been more pronounced or even clinically relevant for certain individuals had one considered a separate analysis of the data of each patient.

Acupuncture Therapy↗
PubMed2000

Isolated congenital nail dysplasia: a new autosomal dominant condition.

OBJECTIVE: Developmental nail abnormalities are extremely heterogeneous, with hereditary isolated conditions being a small and rare subgroup. An unusual congenital nail dysplasia observed in a large South German kindred was characterized clinically to review the question of uniqueness. DESIGN: Case series of affected family members. SETTING: University department of dermatology and houses of patients. PATIENTS: The history and clinical features in 22 affected family members (13 females and 9 males, aged 5 to 74 years) were recorded and documented by photographs. Nail biopsy samples were taken from 2 patients. INTERVENTIONS: None. RESULTS: The pedigree spanning 5 consecutive generations was best compatible with autosomal dominant inheritance with complete penetrance. Nail alterations were mostly present since birth and soon reached an individually variable degree of severity. Affected persons showed longitudinal streaks and thinning of nail plates, mostly of all fingernails and toenails, with some accentuation of the thumbnail and big toenails, poorly developed lunulae, longitudinal angular ridges of individual nail plates occasionally starting proximally from a reddish prominence, platonychia and koilonychia of individual nails often overgrowing the lateral folds, and notches and fissures of the free margins. Histological abnormalities included a prominent granular layer of the nail matrix and epithelial strands and buds extending from the nail bed. There were no associated anomalies. Other nail dystrophies were excluded by differences in clinical and histological features. CONCLUSION: The nail abnormality observed in our family represents a new autosomal dominant disorder for which we propose the term isolated congenital nail dysplasia. Arch Dermatol. 2000;136:1239-1243

Adolescent↗
PubMed2002

Variables influencing bacteriological outcome in patients with streptococcal tonsillopharyngitis treated with penicillin V.

UNLABELLED: Despite the fact that group A streptococci (GAS) remain susceptible to penicillin V (pen V), an increasing rate of bacteriological treatment failures has occurred. A recent study has suggested that the major variables associated with pen V treatment failures were the number of days ill prior to initiation of treatment (<2 days) and age <6 years. In order to study the link between pen V treatment failures and individual variables, we reviewed the files of all children enrolled in four randomised multicentre trials of oral antibiotic therapy, carried out from 1993 to 1999. A standard protocol and follow-up examination were used in these four studies: cultures were obtained 4 days and 1 month after completion of treatment. Total DNA restriction fragment length polymorphism was used to compare pre- and post-treatment GAS isolates. We enrolled 1560 children aged 3 to 12 years, 685 received a 10 day pen V regimen (45 mg/kg per day divided into three doses/day), among them 536 were assessable for bacteriological efficacy at the first and second follow-up visit. We found the only variable associated with penicillin treatment failure was the age of the child when infected. The rate of failure was statistically more important for children younger than 6 years (35.5%, 95% CI 29.9--41.1) than for older children (21.9%, 95% CI 16.9-26.9). CONCLUSION: in this study only young age (<6 years) increases penicillin V treatment failures for group A streptococcal tonsillopharyngitis. This may lead to different antibiotic regimens and follow-up modalities for these targeted patients.

Adolescent↗
PubMed2002

Estimate the time varying brain receptor occupancy in PET imaging experiments using non-linear fixed and mixed effect modeling approach.

Positron-Emission Tomography (PET) is an imaging technology currently used in drug development as a non-invasive measure of drug distribution and interaction with biochemical target system. The level of receptor occupancy achieved by a compound can be estimated by comparing time-activity measurements in an experiment done using tracer alone with the activity measured when the tracer is given following administration of unlabelled compound. The effective use of this surrogate marker as an enabling tool for drug development requires the definition of a model linking the brain receptor occupancy with the fluctuation of plasma concentrations. However, the predictive performance of such a model is strongly related to the precision on the estimate of receptor occupancy evaluated in PET scans collected at different times following drug treatment. Several methods have been proposed for the analysis and the quantification of the ligand-receptor interactions investigated from PET data. The aim of the present study is to evaluate alternative parameter estimation strategies based on the use of non-linear mixed effect models allowing to account for intra and inter-subject variability on the time-activity and for covariates potentially explaining this variability. A comparison of the different modeling approaches is presented using real data. The results of this comparison indicates that the mixed effect approach with a primary model partitioning the variance in term of Inter-Individual Variability (IIV) and Inter-Occasion Variability (IOV) and a second stage model relating the changes on binding potential to the dose of unlabelled drug is definitely the preferred approach.

Animals↗
PubMed2006

Overview of the pharmacogenetics of HIV therapy.

The administration of standard doses of most antiretroviral drugs results in significant variations in plasma drug concentrations among different individuals, influencing antiviral activity as well as incidence of drug-related toxicities. The reasons for this large inter-individual variability in drug levels are multifactorial, and involve differences in metabolism related to gender, concomitant medications, drug compliance, underlying diseases and genetic factors. Pharmacogenetics is the discipline that analyses the genetic basis for the inter-individual variation in the body disposition of drugs. One of its main goals is to give grounds to individualized treatment. The majority of pharmacogenetic traits so far have involved drug metabolism. This is the case for the inherited variation in the pharmacokinetics and pharmacodynamics of drugs such as hydralazine or isoniazid, which is due to polymorphisms in the N-acetyltransferase-2 (NAT2) gene, which allows splitting the population into three categories: slow, intermediate, and fast metabolizers. Pharmacogenetic studies conducted so far with antiretroviral drugs have focussed on metabolizer enzymes at the liver and on transporter proteins on cell membranes. Herein, we review the most relevant metabolizer enzymes and protein transporters, along with the genetic polymorphisms, which seem to influence the pharmacokinetics of antiretroviral drugs, ultimately determining its efficacy and toxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Sex determination: where environment and genetics meet.

In mammals and birds the genetic constitution established at the time of fertilization determines the type of gonad that develops, whereas in all crocodilians and many turtles it is the temperature experienced during the mid-trimester of embryogenesis that initiates gonadal differentiation. Research with the red-eared slider suggests considerable conservation in the genetic cascades that underlie the sex determination process in vertebrates and, further, that the patterns of expression of these genes appear to reflect phylogenetic relationships, with turtles being more similar to mammals than they are to birds and crocodilians. After the determination and differentiation of an individual's gonadal sex, epigenetic forces shape those morphological, physiological, and behavioral traits that characterize each individual's unique sexuality. Research with the leopard gecko thus relates to the fundamental question of what factors determine individual variability, particularly as it relates to sexually dimorphic behaviors. Taken together, this research illustrates how sexuality depends on sex, but sex should not be confused with sexuality. That is, sex is merely a means of categorizing individuals or gonads, whereas sexuality serves as a descriptor of concordant traits each of which is typically sexually dimorphic in its expression.

Alligators and Crocodiles↗
PubMed1996

Clonal stability of blood cell lineages indicated by X-chromosomal transcriptional polymorphism.

The idea that stem cells oscillate between a state of activity and dormancy, thereby giving rise to differentiating progeny either randomly or in orderly clonal succession, has important implications for understanding normal hematopoiesis and blood cell dyscrasias. The degree of clonal stability in individuals also has practical implications for the evaluation of clonal lymphomyeloproliferative diseases. To evaluate the clonality pattern of the different types of blood cells as a function of time we have validated the applicability, sensitivity, and reproducibility of a thermostable ligase reaction to detect transcripts of the G6PD allele on the active X-chromosome in normal heterozygous females. While the ratio of the two X-chromosome-derived allelic transcripts varied widely among hemopoietic tissues in a given individual, this allelic ratio was virtually identical in all types of mature myeloid and lymphoid cells. Longitudinal studies indicated constancy of the G6PD allelic ratio in blood cells over a 912-d period of observation in healthy females. The individual variability observed in this allelic ratio suggests that the progeny of a relatively small number of original embryonic hemopoietic stem cells, approximately eight, contribute to the sustained production of all types of blood cells in healthy individuals.

Alleles↗
PubMed1991

Recurrent and persistent diarrhoea in a rural Zimbabwean community: a prospective study.

Prospective surveillance of patterns of diarrhoeal disease was conducted in a cohort of 204 young children living in a rural community in Zimbabwe. Trained field assistants recorded morbidity data obtained by weekly recall of mothers. Diarrhoea was defined by a commonly used local word, and a diarrhoea-free gap of three or more days was taken to signify a new attack. Diarrhoea was common in this study population with a peak incidence between 6 and 18 months of age. There was, however, wide individual variability in diarrhoea attack rates (range 0 to 20 attacks) during the 22 month study period. Whilst only 6 per cent of the recorded diarrhoea episodes were persistent (lasting longer than 14 days), a high proportion (26 per cent) of subjects had at least one attack of persistent diarrhoea (PD) during follow up. Children who had frequent attacks of acute diarrhoea also tended to have PD; PD was rare in those with few attacks. Thus, within this uniformly deprived African community, there were individuals who had a much higher susceptibility to diarrhoea compared to others. An understanding of this variability may point the way towards more effective interventions in the control of diarrhoeal disease.

Child, Preschool↗
PubMed2006

Measurements of biomarker levels in flounder (Platichthys flesus) and blue mussel (Mytilus trossulus) from the Gulf of Gdańsk (southern Baltic).

In the framework of the EU funded BEEP project a set of biomarkers, gross morphometric indices and tissue concentrations of selected organic pollutants were measured in flounder (Platichthys flesus) and mussels (Mytilus trossulus) collected twice a year (April and October) from three sites in the inner Gulf of Gdańsk between autumn 2001 and spring 2003. In flounder, seasonal differences in most biomarkers were observed, but no correlations with tissue pollutant levels could be found. In mussels, highly variable levels in biomarker responses were seen, but no clear seasonal or spatial trends, directly related to tissue concentrations, could be established. The observed biomarkers distribution the study sites are probably mostly caused by interannual, seasonal and individual variability and, in case of flounder, possibly by exchange of stocks between the sampling sites.

Acetylcholinesterase↗
PubMed1999

Visual impairment and REP-1 gene mutations in Japanese choroideremia patients.

Choroideremia (CHM), an X-linked recessive hereditary disease, is an intractable chorioretinal dystrophy. The rate of disease progression of CHM reportedly shows considerable variability. A number of mutations involving the gene that codes for Rab escort protein-1 (REP-1) have been detected in CHM patients. We have analyzed REP-1 gene mutations of Japanese CHM patients. The present study was designed to investigate the clinical variability and the genotype to phenotype relationship in 15 Japanese CHM patients referred to the Department of Ophthalmology of Juntendo University Hospital. The clinical investigation of visual acuity, visual field, color vision and refraction revealed inter-individual variability. Mutation analyses of the REP-1 gene revealed 10 types of mutations in 13 patients from 11 families, including an insertion, small deletions, nonsense mutations and an A to CC mutation. In 13 CHM patients with detectable REP-1 gene mutations, no relationship of genotype to phenotype was detected. At present, we consider the REP-1 genotype to be an unreliable prognostic factor for counseling of CHM patients. In two patients from one family, no mutations were detected in coding regions of the REP-1 gene. These patients may have intron mutations of the REP-1 gene, not detectable by the techniques employed in this study, or other causative genes. Both were observed to have somewhat slower disease progression than the other 13 patients. More advanced analyses are necessary to answer questions regarding the genotype-phenotype relationship in CHM patients.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Histological changes in chronic experimental aneurysms surgically fashioned in sheep.

After experimental venous pouch saccular aneurysms were surgically fashioned on common carotid arteries of sheep, the ensuing long term hemodynamic effects on the vessel walls were examined up to seven years postoperatively. The aneurysms became more spherical rather than remaining elongated, enlarging at variable, individual rates. Venous sac changes were similar to phlebosclerosis in human veins with progression to sclerotic walls and loss of conventional mural architecture at most sites. Lipid accumulation, despite low serum cholesterol levels, calcification, intimal tears of variable depth, mural dissection and secondary mural thrombosis, occurred as in human atherosclerosis and indicated this model's potential for studies of such pathological disorders and the pathological effects of enhanced hemodynamic stress.

Aneurysm↗
PubMed1992

Paradoxical early lengthening and subsequent linear shortening of the QT interval in response to exercise.

The QT responses to exercise during ventricular pacing were evaluated in 12 patients in whom permanent pacemakers were implanted for complete heart block. The initial response of the QT to exercise was a paradoxical lengthening during the first minute of exercise (mean 4.8 ms P < 0.01). Thereafter, the QT was found to shorten in a linear fashion in response to increasing exercise, both in terms of exercise duration (r = 0.787; P < 0.001) and atrial rate (r = 0.712; P < 0.001). The total QT shortening with exercise was small (20 ms for a mean increase in atrial rate of 60 beats.min-1) and displayed substantial inter-individual variability (9-31 ms). These results explain some of the limitations of the QT pacemaker, and provide insights in to the dynamics of the QT response, which may help tailor the programming of these systems to the individual patient.

Adult↗
PubMed2005

Advanced qRT-PCR technology allows detection of the cholecystokinin 1 receptor (CCK1R) expression in human pancreas.

OBJECTIVES: To help clarify the controversy over the detection of expression of the cholecystokinin 1 receptor (CCK1R; CCKAR) in human pancreas. METHODS: Applied qRT-PCR to detect CCK1R expression using the SYBR green/Smart Cycler II and the QZyme oligonucleotide/ABI PRISM 7500 systems to detect CCK1R expressed message in highly purified cDNAs from human pancreas and other tissues. Samples of normal pancreas were obtained at operation (pancreaticoduodenectomy; Whipple's procedure) and used to ascertain the expression of CCK1R in human tissue and investigate donor individual variability in expression levels by semi-quantitative RT-PCR and scanning densitometry. RESULTS: We present molecular evidence obtained with advanced qRT-PCR technology that clearly establishes CCK1R expression in human pancreas. Amplification variation in individual human samples is documented here. By targeting different stretches of the sequence with several primer pairs, it was observed that SYBR green qRT-PCR failed to amplify efficiently over GGA-and GAA-rich nucleotide triplet regions, leading to false negative results. The QZyme system quantified the expression with the following distribution: stomach > small intestine approximately colon > brain approximately kidney > pancreas. CCK1R expression levels varied from undetectable, to high levels of expression, in individual samples collected from surgical specimens. CONCLUSION: CCK1R message can be conclusively detected and quantified in human pancreas cDNA by targeting the appropriate nucleotide sequence regions of this gene.

DNA, Complementary↗
PubMed2002

Nighttime sleep-wake patterns and self-soothing from birth to one year of age: a longitudinal intervention study.

BACKGROUND: The objectives of this study were to: (1) describe the longitudinal development of sleep-wake patterns of solitary-sleeping infants from 1 to 12 months of age, (2) identify effects on sleep patterns and on self-soothing behaviors of introducing a novel sleep aid, and (3) identify predictive factors of self-soothing at 12 months using a transactional model as a guide. METHODS: Eighty infants' nighttime sleep-wake patterns and associated variables were studied at 5 times across the first year of life using videosomnography and questionnaires. RESULTS: Sleep-wake state developmental changes, as reported in investigations of infant sleep, were replicated, although a great deal of individual variability in the development of all sleep-related variables was noted. No major effects on sleep or on self-soothing behavior were evident from the introduction of the novel sleep aid. Three variables were identified as significant predictors of self-soothing at 12 months: decreasing amounts of time spent out of crib across the first year, high levels of quiet sleep at birth, and longer parental response times to infant awakenings at 3 months. CONCLUSIONS: These data lend preliminary support for the transactional model and suggest that infant and parental factors interact to influence the development of self-soothing.

Circadian Rhythm↗