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PubMed1995

Major geometric variations between multiple high-dose-rate applications of brachytherapy in cancer of the cervix: frequency and types of variation.

PURPOSE: To evaluate major geometric variations in multiple intracavitary applications for carcinoma of the cervix. MATERIALS AND METHODS: Orthogonal radiographs were reviewed of 17 consecutive patients with carcinoma of the cervix treated with 70 applications of high-dose-rate brachytherapy. In seven patients, conscious sedation was used for all applications. In 10 patients, general anesthesia was used for the first application and conscious sedation for subsequent applications. Major geometric variation between applications in axis, length, and slippage in tandem placement and separation, packing, and slippage in colpostats placement were reviewed. A major variation was defined as more than 1.0-cm deviation. RESULTS: Major variations between applications occurred more commonly in colpostats placement than in tandem placement. For tandems, the rates of variation were 5.7% in axis, 4.3% in length, and 1.4% in slippage. For colpostats, rates of variation were 7.1% in separation, 25.7% in vaginal packing, and 7.1% in slippage. No consistent pattern of variation was found between applications except in vaginal packing. CONCLUSION: Awareness of geometric variations should improve proper placement of intracavitary applicators for brachytherapy.

Anesthesia, General↗
PubMed1991

Priority of peak circadian variation of bronchial responsiveness to the trough of circadian variation of bronchial caliber in asthmatic children.

To study the temporal relation between the peak of circadian variation of bronchial responsiveness and the trough of circadian variation of bronchial caliber, we performed seven inhalation challenges with histamine at 4-h intervals in six stable asthmatic children aged eight to ten years. Bronchial responsiveness was expressed as PC20. Coefficient of variation of baseline FEV1 within the study day was less than 7 percent in all. The trough of FEV1 variation by cosinor analysis ranged from 02.50 to 11.99 h (mean, 05.66). All had both significant (p less than 0.05) or marginally significant (0.05 less than p less than 0.1) cosinusoidal rhythm of PC20 and two or more doubling concentration differences between the highest and lowest PC20s. The trough of PC20 variation ranged from 16.32 to 02.87 h (mean, 22.30). There was a significant (p less than 0.05) difference between troughs of FEV1 and PC20 variations. We conclude that the peak of circadian variation of bronchial responsiveness precedes the trough of circadian variation of bronchial caliber in asthmatic children.

Asthma↗
PubMed2005

[Anatomic variations of the paranasal sinuses detected by computed tomography and the relationship between variations and sex].

OBJECTIVES: In this study, we evaluated anatomic variations detected by computed tomography (CT) of the paranasal sinuses and their relationship with sex. PATIENTS AND METHODS: Computed tomography scans of the paranasal sinuses of 464 patients (206 males, 258 females; mean age 37.5 years; range 4-87 years) were retrospectively analyzed. In cases requiring further investigation, axial and sagittal views were obtained using multiplanar reformatted images. Bone window images were also obtained particularly to evaluate dehiscence variations. Paranasal sinus variations were classified into eight subgroups according to their origins (nasal septum, ethmoid cells, maxillary sinus, uncinate process, frontal and sphenoid sinuses, orbit, and nasal concha). The frequency of variations was compared between male and females. RESULTS: The most common anatomic variation was agger nasi cells (80.4%) followed by pneumatization of the middle concha (37%). The least encountered variations were pneumatization of the inferior turbinate, bony dehiscence of the ethmoidal roof, and duplication of the middle and superior turbinates. The frequency of variations did not differ significantly with respect to gender (p>0.05) except for frontal hypoplasia, which was more often in females (p<0.05). CONCLUSION: Axial and sagittal views using multiplanar reformatted images can be helpful in eliminating artefacts and in identifying variations of the paranasal sinuses. Utilization of soft tissue and bone windows, when necessary, may facilitate evaluation of dehiscence abnormalities.

Adolescent↗
PubMed2001

Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite.

African trypanosomes are unicellular, eukaryotic parasites that live extracellularly in a wide range of mammals, including humans. They have a surface coat, composed of variant surface glycoprotein (VSG), which probably is essential and acts as a defence against general innate immunity and against acquired immunity directed at invariant surface antigens. In effect, the VSG is the only antigen that the host can target, and each trypanosome expresses only one VSG. To counter specific antibodies against the VSG, trypanosomes periodically undergo antigenic variation, the change to expression of another VSG. Antigenic variation belongs to the general survival strategy of enhanced phenotypic variation, where a subset of 'contingency' genes of viruses, bacteria and parasites hypermutate, allowing rapid adaptation to hostile or changing environments. A fundamental feature of antigenic variation is its link with the population dynamics of trypanosomes within the single host. Antigenic variants appear hierarchically within the mammalian host, with a mixture of order and randomness. The underlying mechanisms of this are not understood, although differential VSG gene activation may play a prominent part. Trypanosome antigenic variation has evolved a second arm in which the infective metacyclic population in the tsetse fly expresses a defined mixture of VSGs, although again each trypanosome expresses a single VSG. Differential VSG expression enhances transmission to new hosts, in the case of bloodstream trypanosomes by prolonging infection, and in the metacyclic population by generating diversity that may counter existing partial immunity in reservoir hosts. Antigenic variation employs a huge repertoire of VSG genes. Only one is expressed at a time in bloodstream trypanosomes, as a result of transcription being restricted to a set of about 20 bloodstream expression sites (BESs), which are at chromosome telomeres. Only one BES is active at a time, probably through transcriptional elongation being inhibited in the silent BESs. Although transcriptional switching between BESs can effect a VSG switch, the most prolific switch route involves homologous recombination of deoxyribonucleic acid, usually by the copying of a silent gene into a BES. Hierarchical expression of VSGs may be dictated in part by the different types of locus occupied by VSG genes. The VSG genes expressed in the metacyclic population also occupy telomeric sites, which appear to be derived from BESs but have a simpler structure. Their differential expression is achieved by random transcriptional activation; the detailed story requires direct study of the metacyclic stage itself. Available evidence suggests that the VSG originated as a surface receptor, and it can be proposed that a number of selective events have contributed to the evolution of the complex, multisystem phenomenon that antigenic variation has become.

Animals↗
PubMed1997

Common genomic variation in the APOC3 promoter associated with variation in plasma lipoproteins.

We hypothesized that common genomic variation that affected the expression and/or function of the products of the APOC3, APOE, FABP2, and PON1 genes would be associated with variation in biochemical phenotypes in a previously unstudied human sample. We determined genotypes of functional genomic variants of APOC3, APOE, FABP2, and PON1 in 509 adult aboriginal Canadians from an isolated community in Northern Ontario. We tested for genotype associations with plasma lipoprotein traits. We found that (1) common variation at nucleotide -455 of the APOC3 promoter was associated with variation in plasma triglycerides (P = .006) and (2) common variation of APOE determining plasma isoforms of apo E was associated with variation in plasma apo B (P = .009). Analysis of subjects classed by APOC3 markers showed that homozygosity for presence of a C at nucleotide -455 and a T at nucleotide -482 was associated with significantly increased plasma triglycerides in both men and women. Furthermore, this allele was approximately twice as frequent in subjects within the highest quartile of plasma triglycerides as in subjects within the lowest quartile. Since the DNA variation detected by the APOC3 markers affects in vitro expression of the gene product, it is possible that the marker itself caused the associations. However, the associations could also have resulted from linkage disequilibrium with other functional variants in APOC3 or the closely linked APOA1 and/or APOA4 genes.

Adolescent↗
PubMed2003

Spatial and temporal variation in mortality of newly settled damselfish: patterns, causes and co-variation with settlement.

Local abundance and dynamics of sedentary species with a dispersing life stage reflect factors that influence input and loss rates to patches of suitable habitat. For reef fishes, more attention has focused on sources of variation in input (larval settlement) than on patterns and causes of subsequent losses. We estimated spatial and temporal variation in juvenile mortality of a tropical damselfish, yellow-tail dascyllus (Dascyllus flavicaudus; Pomacentridae), using a fixed density experiment that was repeated 5 times at the same eight mid-lagoon localities at Moorea, French Polynesia. There was little temporal variation in the overall percent of outplanted fish lost in 48 h among five time periods (range: 32-37%), whereas there was substantial variation among the sites in the average percent lost (range: 16-56%). Differences in loss rates among the sites were highly consistent among the time periods. Densities of predators of juvenile dascyllus varied substantially among the eight sites and were highly correlated with loss rate of dascyllus. We used the empirically derived relationship between predator density and damselfish loss rate to predict the loss rate of dascyllus at four additional sites, and there was excellent agreement between the predicted and observed loss rates. There was a strong positive relationship between predator densities at the 12 sites and structural attributes of the reefs that do not change on a fast time scale, suggesting why there was strong spatial and weak temporal variation in mortality rates, with no interaction between spatial and temporal variation. Natural settlement rates of yellow-tail dascyllus and of a close congener (humbug dascyllus, D. aruanus) varied among the sites, and settlement of the two species was inversely correlated (r=-0.68). Settlement of these species was not statistically correlated with variation in mortality rate, but there was a weak trend for settlement of yellow-tail dascyllus to be greater at sites with higher mortality (r=0.27), and for settlement of humbug dascyllus to be greater at sites with lower mortality (r=-0.32). We calculated that even these weak co-variances could reduce (yellow-tail dascyllus) or increase (humbug dascyllus) the spatial variance in density of 48-h-old recruits arising at settlement by 19 and 27% respectively. Taken together, the findings suggest that the interactions between and relative contributions of input and loss processes can differ substantially over a scale of a few kilometers, resulting in a mosaic of local patches characterized by different abundances and dynamics.

Analysis of Variance↗
PubMed1985

Intra-individual variation: significant changes in parameters of lipid and carbohydrate metabolism in the individual and intra-individual variation in different test populations.

Fasting serum triglyceride, cholesterol, HDL cholesterol, HDL 2&3 cholesterol, fasting plasma glucose and insulin and haemoglobin A1 were measured under standardised conditions in a group of laboratory volunteers. Intra-individual variation was calculated for each parameter from weekly measurements on at least eleven successive occasions, and the minimum change in each parameter that would be significant at the level P less than 0.05 was calculated. A further study compared intra-individual variation in different test populations. Data from the group of laboratory volunteers were taken to represent intra-individual variation under standard test conditions with an informed test population and data from a group of regularly monitored out-patients undergoing drug therapy for hypercholesterolaemia were taken to represent intra-individual variation under standard conditions in a typical test population. A group of in-patients under strict dietary control provided information on variation under extreme standardisation of test conditions. Intra-individual variation was greatest for all parameters in the outpatient population. Extreme standardisation of test condition reduced intra-individual variation beyond that of the laboratory volunteers only in the case of serum triglyceride.

Blood Glucose↗
PubMed2006

VKORC1 gene variations are the major contributors of variation in warfarin dose in Japanese patients.

OBJECTIVES: To compare the genetic and clinical factors that cause large interpatient variability and ethnic differences in warfarin efficacy, we investigated variations of the VKORC1, CYP2C9, and CYP2C19 genes in Japanese subjects. Furthermore, we evaluated the genetic variations and clinical data as contributors of variation in warfarin maintenance dose. METHODS: Gene variations of VKORC1, CYP2C9, and CYP2C19 in 125 patients treated with warfarin and 114 healthy subjects were analyzed. The daily dose of warfarin, concentrations of S- and R-warfarin in plasma, and prothrombin time expressed as the international normalized ratio were used as the pharmacokinetic and pharmacodynamic indices. Data were evaluated by a multivariate analysis method. RESULTS: Three missense mutations (47 G>C, 113 A>C, and 1338 A>G) in VKORC1 were newly identified in the Japanese population. The 113 A>C (Asp38Ser) variant decreased the warfarin dose requirement from 3.33 +/- 1.54 mg/d (n = 122) to 1.5 mg/d (n = 1). The variants -1639 G>A in the 5'-upstream region, 1173 C>T in intron 1, and 1542 G>C in intron 2 were in complete linkage disequilibrium, and the frequency of the -1639 G>A variation was only 0.8%, which contrasts with the frequency (39.8%-45.8%) reported previously for white persons. The dose of warfarin was larger in the VKORC1 -1639 GA genotype group (4.55 +/- 1.75 mg/d, P < .001) than in the -1639 AA group (2.94 +/- 1.15 mg/d). The mean daily dose of warfarin was lower in subjects with CYP2C9*1/*3 (1.86 +/- 0.80 mg/d, P = .007) than in subjects with CYP2C9*1/*1 (3.36 +/- 1.43 mg/d). When the relative contributions of the VKORC1 variants, CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3, as well as the clinical characteristics of the patients, diagnoses, and concurrent medications, were compared, the VKORC1 -1639 GA genotype group accounted for 16.5% and CYP2C9 variants accounted for 13.4% of variation in warfarin dose. CONCLUSION: The ethnic difference in warfarin maintenance dose was mainly dependent on the linked VKORC1 variants. Genotyping of -1639 G>A of the VKORC1 gene could be clinically important for predicting individual variability in anticoagulant responses to warfarin.

Adult↗
PubMed2000

Maintenance of genetic variation in phenotypic plasticity: the role of environmental variation.

We study genetic variation in phenotypic plasticity maintained by a balance between mutation and weak stabilizing selection. We consider linear reaction norms allowing for spatial and/or temporal variation in the environments of development and selection. We show that the overall genetic variation maintained does not depend on whether the trait is plastic or not. The genetic variances in height and slope of a linear reaction norm, and their covariance, are predicted to decrease with the variation in the environment. Non-pleiotropic loci influencing either height or slope are expected to decrease the genetic variance in slope relative to that in height. Decrease in the ratio of genetic variance in slope to genetic variance in height with increasing variation in the environment presents a test for the presence of loci that only influence the slope, and not the height. We use data on Drosophila to test the theory. In seven of eight pair-wise comparisons genetic variation in reaction norm is higher in a less variable environment than in a more variable environment, which is in accord with the model's predictions.

Alleles↗
PubMed1985

Genome size variation among north american minnows (Cyprinidae). I. Distribution of the variation in five species.

Genome sizes (nuclear DNA contents) were examined spectrophotometrically from ten individuals of each of five species of North American cyprinid fishes (minnows). The distributions of DNA values both within and between the five species were essentially continuous and normal. Differences between individuals within populations were significant and contributed to approximately 16 per cent of the total variation. Variation between individuals within species ranged from 4.7-13.5 per cent and averaged ca. 7.4 per cent. Variation between species ranged from 0-9.5 per cent and the average difference between any species pair was ca. 4.6 per cent. Statistical analyses showed that the methodology used was sufficient to detect significant differences in genome size as small as 2-3 per cent. Consideration of these data lead to the following tentative conclusions: (i) changes in genome size in cyprinids appear small in amount, frequent in occurrence, to involve both gains and losses of DNA, and to be cumulative and independent in effect; (ii) differences within and between cyprinid taxa are likely the result of accumulations of small changes in DNA quantity; and (iii) the primary focus of quantitative DNA variation in cyprinids is between individuals within populations. The extent of DNA quantity variation which occurs within species would appear to preclude any direct relationship between genome size variation and many of the organismal parameters (including speciation) which differentiate the five species. In short, the data suggest that a significant fraction of the cyprinid genome, perhaps more than 10 per cent, is free to vary quantitatively without phenotypic constraint or biological consequence. This fraction is considerably larger than that theoretically needed for the structural gene component.

Animals↗
PubMed1998

Genetic variation in paraoxonase-2 is associated with variation in plasma lipoproteins in Canadian Oji-Cree.

We report studies of the association between genetic variation in PON2 and variation in plasma quantitative traits in a sample of 334 non-diabetic Oji-Cree. We detected associations between PON2 variation in codon 148 (Ala --> Gly) and variation in fasting plasma concentrations of total and low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B. In particular, homozygotes for a PON2 allele that encoded A148 had significantly higher plasma total, LDL cholesterol and apo B than subjects having the other two genotypes (p < 0.01). Taken together, our results suggest that common genetic variation on chromosome 7q21.3-22.1 in PON2 is associated with significant variation of intermediate traits in plasma lipoprotein metabolism.

Adult↗
PubMed1995

Genetic variation on chromosome 1 associated with variation in body fat distribution in men.

BACKGROUND: Interindividual variation in fat deposition in swine is determined by loci on porcine chromosome 4, which are contained in a region that is syntenic with part of the long arm of human chromosome 1. We hypothesized that genomic variation of chromosome 1q would be associated with variation in the ratio of waist-to-hip circumference in male North American Hutterites, a genetic isolate characterized by significant relatedness and sharing of environmental factors. METHODS AND RESULTS: In 316 male Hutterites, we tested for phenotype-genotype association of two DNA polymorphisms on chromosome 1q and the ratio of waist-to-hip circumference. We included control loci on 10 other chromosomes in the multivariate model. We observed that DNA variation on chromosome 1q was significantly associated with variation in the ratio of waist-to-hip circumference in men (P = .0029). CONCLUSIONS: The association of DNA variation chromosome 1q with the ratio of waist-to-hip circumference in male Hutterites suggests that there are important structural elements in this genomic region that have a functional impact on body fat distribution.

Adipose Tissue↗
PubMed1998

Intrapopulational body size variation and cranial capacity variation in Middle Pleistocene humans: the Sima de los Huesos sample (Sierra de Atapuerca, Spain).

A sexual dimorphism more marked than in living humans has been claimed for European Middle Pleistocene humans, Neandertals and prehistoric modern humans. In this paper, body size and cranial capacity variation are studied in the Sima de los Huesos Middle Pleistocene sample. This is the largest sample of non-modern humans found to date from one single site, and with all skeletal elements represented. Since the techniques available to estimate the degree of sexual dimorphism in small palaeontological samples are all unsatisfactory, we have used the bootstraping method to asses the magnitude of the variation in the Sima de los Huesos sample compared to modern human intrapopulational variation. We analyze size variation without attempting to sex the specimens a priori. Anatomical regions investigated are scapular glenoid fossa; acetabulum; humeral proximal and distal epiphyses; ulnar proximal epiphysis; radial neck; proximal femur; humeral, femoral, ulnar and tibial shaft; lumbosacral joint; patella; calcaneum; and talar trochlea. In the Sima de los Huesos sample only the humeral midshaft perimeter shows an unusual high variation (only when it is expressed by the maximum ratio, not by the coefficient of variation). In spite of that the cranial capacity range at Sima de los Huesos almost spans the rest of the European and African Middle Pleistocene range. The maximum ratio is in the central part of the distribution of modern human samples. Thus, the hypothesis of a greater sexual dimorphism in Middle Pleistocene populations than in modern populations is not supported by either cranial or postcranial evidence from Sima de los Huesos.

Adult↗
PubMed1998

The value of the coefficient of variation in assessing repeat variation in ECG measurements.

AIMS: The coefficient of variation is a popular measure for describing the amount of repeat variability present in ECG measurements from recording to recording. However, it can be misleading. The aim of the present study was to assess repeat variation (reclassification) in computer measured ECG criteria, i.e. positive to negative or vice versa, and compare this with the coefficient of variability. METHODS AND RESULTS: Two ECGs were obtained from each of 295 patients, one day apart, and separately from a further 364 patients, several minutes apart. All patients were considered to be in a stable condition. Estimates of the coefficients of variation were obtained for a number of ECG parameters used in the diagnosis of left ventricular hypertrophy. Corresponding reclassification rates of relevant ECG criteria were also calculated. Large coefficients of variation were observed in voltage parameters, e.g. R in V5 (20% for day-to-day recordings and 6% for minute-to-minute recordings) while the corresponding reclassification rates were 8% and 0% respectively. The repeat variation in the diagnosis of left ventricular hypertrophy was up to 5% for day-to-day recordings and up to 3% for minute-to-minute recordings based on several different criteria. CONCLUSION: A large coefficient of variation in a particular variable does not necessarily correspond to a high reclassification rate. A better measure of the impact of ECG variability for a particular measurement is obtained from its reclassification rate. In turn, this may have a minimal effect on the overall diagnosis of a particular abnormality.

Adult↗
PubMed1998

Association of variation in hepatic lipase activity with promoter variation in the hepatic lipase gene. The LOCAT Study Invsestigators.

The associations between six genetic polymorphisms in the hepatic lipase (HL) gene (LIPC) and variation in postheparin HL activity and fasting serum lipoproteins were evaluated in 395 male Finnish coronary heart disease patients with HDL cholesterol concentrations </= 1.1 mmol/liter. The LIPC promoter polymorphism at position -514 was highly significantly associated with variation in HL activity (P = 0.0000008), with mean activities of 20.4, 17.5, and 13.2 mumol free fatty acid/ml per hour in subjects having C/C, C/T, and T/T genotypes, respectively. Furthermore, the triglyceride content of low density lipoprotein, intermediate density lipoprotein and HDL, and the cholesterol content of intermediate density lipoprotein were found to be associated with variation at LIPC position -514. However, there was no association of this polymorphism with coronary heart disease. These data suggest that the LIPC promoter variation is likely to be the basis for variation in HL activity, which underlies the variation in serum lipoprotein phenotypes in this sample.

Cholesterol↗
PubMed1976

Factors contributing to intra-individual variation of serum constituents: Physiological day-to-day variation in concentrations of 10 specific proteins in sera of healthy subjects.

Using an automated immunoprecipitin method, we assayed human sera for 10 proteins: haptoglobin, orosomucoid, transferrin, alpha1 antitrypsin, alpha2-macroglobulin, IgG, IGa, IgM, complement C3, and complement C4. Blood from 14 healthy subjects (25-40y) was sampled on six separate days. From each venipuncture serum was divided into four eliquots; two were assayed on the day of venipuncture and two were frozen and kept until the end of the study, when all of the frozen samples were analyzed in one batch. With this experimental design, batch-to-batch analytical variation could be estimated, and we avoided confounding it with the biological variation. Data analysis was based on the analysis of variance technique. The average physiological intra-individual coefficient of variation ranged from 2.5% for transferrin to 11.1% for orosomucoid. THe interindividual variation ranged from 9.5% for transferrin to 70.5% for haptoglobin and the ratio between intra-individual variation and interindividual variation ranged from 0.66 for IgM to 0.26 for orosomucoid and transferrin.

Adult↗
PubMed1994

Between-subjects variation in energy expenditure: estimation of the effect of variation in organ size.

The between-subjects variation in energy expenditure over 24 h at a fixed physical activity and corrected for differences in fat and fat-free mass has recently been determined to be 6-7%. New data on the variation between subjects of the weights of the brain, liver, kidneys, heart and spleen together with estimates of the energy expenditure of these organs were used to calculate the part of the between-subjects variation in energy expenditure at a fixed physical activity that is due to this variation alone. The results show that this variation is close to 5%. Thus, a very considerable part of the total between-subjects variation can be explained by differences in the composition of the fat-free mass.

Adolescent↗