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Inter- and intra-individual variation in the metabolism of methaqualone in man after a single oral dose.

The urinary excretion of five C-monohydroxy metabolites and the N-oxide metabolite of methaqualone in the 24 h period immediately after oral dosing with 250 mg methaqualone (Melsed) has been measured in ninteen healthy adults (13 male, 6 female) to assess interindividual variations and in five adults (3 male, 2 female) on five separate occasions to assess intraindividual variation. The overall importance of the six metabolites was 4'-hydroxy greater than N-oxide greater than 2'-hydroxymethyl greater than 3'-hydroxy greater than 6-hydroxy = 2-hydroxymethyl. Variations in this order both within the 24 h period and within each of the three eight-hour periods constituting the 24 hours were minor and variations in the absolute amount of each metabolie excreted ranged from two to three-fold. Intraindividual variations were generally smaller than interindividual variations and for each individual the pattern of metabolism was similar on the five occasions. There is evidence that the C-oxidation of methaqualone may be more sensitive to cyclical variations in hormone levels than is N-oxidation.

Adult↗

Inter- and intra-individual sources of variation in levels of urinary styrene metabolites.

OBJECTIVE: Given the paucity of studies that have examined variability in biological measures of exposure to workplace contaminants, we quantified the intra- and inter-individual sources of variation in urinary levels of mandelic acid (MA) and phenylglyoxylic acid (PGA) among workers exposed to styrene. A secondary objective was to examine effects of job task and the timing of sampling during the workweek on the variation in workers' urinary styrene metabolite levels. METHODS: As part of routine biological monitoring, a total of 1,714 measurements of MA and PGA collected from 331 workers between 1985 and 1999 from eight reinforced-plastics plants were abstracted from laboratory reports. To evaluate sources of variation in levels of urinary styrene metabolites, we applied random-effects models. The influence of job task and day of sampling on metabolite levels was examined using mixed-effects models. RESULTS: PGA levels were characterized by less variation than levels of MA, as were metabolite levels expressed in terms of urinary creatinine concentration. The relative magnitude of the inter-individual to the intra-individual source of variation was generally higher for post-shift urine samples than for pre-shift urine samples. As expected, urinary metabolite levels were highest for laminators and for samples collected at the latter end of the workweek. Owing to the effects of variation from day-to-day, estimates of workers' exposures that rely on single measurements would generally perform poorly in a regression analysis designed to examine effects resulting from chronic exposure. However, the bias in an observed slope coefficient would be diminished if a second or third urine sample were collected. CONCLUSIONS: Quantification of the intra- and inter-individual sources of variation provides useful information that can be used to design optimal sampling strategies, which would allow for the collection of sufficient data to estimate workers' exposures reliably when evaluating health risks associated with occupational contaminants.

Glyoxylates↗

An empirical analysis of mt 16S rRNA covarion-like evolution in insects: site-specific rate variation is clustered and frequently detected.

The structural and functional analysis of rRNA molecules has attracted considerable scientific interest. Empirical studies have demonstrated that sequence variation is not directly translated into modifications of rRNA secondary structure. Obviously, the maintenance of secondary structure and sequence variation are in part governed by different selection regimes. The nature of those selection regimes still remains quite elusive. The analysis of individual bacterial models cannot adequately explore this topic. Therefore, we used primary sequence data and secondary structures of a mitochondrial 16S rRNA fragment of 558 insect species from 15 monophyletic groups to study patterns of sequence variation, and variation of secondary structure. Using simulation studies to establish significance levels of change, we found that despite conservation of secondary structure, the location of sequence variation within the conserved rRNA structure changes significantly between groups of insects. Despite our conservative estimation procedure we found significant site-specific rate changes at 56 sites out of 184. Additionally, site-specific rate variation is somewhat clustered in certain helices. Both results confirm what has been predicted from an application of non-stationary maximum likelihood models to rRNA sequences. Clearly, constraints on sequence variation evolve and leave footprints in the form of evolutionary plasticity in rRNA sequences. Here, we show that a better understanding of the evolution of rRNA sequences can be obtained by integrating both phylogenetic and structural information.

Animals↗

Variation in scanning line source sensitivity: a significant source of error in simultaneous emission-transmission tomography.

Transmission measurement is recommended in order to accurately correct for attenuation in myocardial single-photon emission tomography (SPET) studies. It is important that transmission studies are artefact-free, otherwise the attenuation-corrected SPET studies may also be affected. An assumption in transmission studies is that the measured transmission in air used as a reference scan is valid for any camera orientation. Variation in transmission source sensitivity (both source efficiency and detector sensitivity) with rotation negates this assumption and can produce errors that result in significant reconstructed artefacts. The aim of this study was to investigate the variation in transmission source sensitivity with a view to defining action thresholds for routine quality control tests. Transmission measurements in air were recorded on two commercial scanning line source installations for the 180 degrees arc normally used in myocardial SPET. Significant variation in transmission source sensitivity was observed on one system (exceeding 30%). Comparison was also made with the reference scan recorded at a different time at a fixed angular location. Both systems demonstrated measurable variation between transmission counts and the corresponding reference scan. A simulation study was undertaken using patient data to determine the influence of transmission sensitivity variation on reconstructed myocardial counts. To maintain reconstructed counts to within 15% of that obtained with artefact-free transmission data, the variation in transmission sensitivity with rotation needed to be within 5%. These results have necessitated the addition of quality control procedures and specific maintenance procedures to attempt rectification of the problem. Variation in transmission source sensitivity with rotation is a potential source of error in attenuation-corrected SPET. Steps should be taken to stabilise transmission source mountings so as to minimise this potential source of error.

Algorithms↗

Intra-individual variation in the metabolism of inorganic arsenic.

OBJECTIVE: Inorganic arsenic is metabolized to methylarsonic acid (MMA) and dimethylarsinic acid (DMA), which are excreted in the urine. Previous studies have shown a marked inter-individual variation in the metabolism, but the within-person variation is unknown. Therefore, we determined the variation in the relative amount of urinary arsenic metabolites, i.e., inorganic arsenic, MMA and DMA, over time in women living in an Andean village with elevated arsenic levels in drinking water. METHODS: For our investigation of the individual day-to-day variation, daily spot urine samples were collected (at the same time of the day) for 5 consecutive days by 15 women. For our investigation of the within-day variation, seven women collected all the urine voided over a 72-h period, each voided into a separate container. RESULTS: Repeated measures analysis of variance (ANOVA) revealed no significant day-to-day variation, either in the relative distribution of inorganic arsenic metabolites (inorganic arsenic, MMA and DMA), or in the concentration of the metabolites. However, the percentage of DMA was slightly higher (on average 5.0%; P=0.003) and the percentage of inorganic arsenic lower (on average 5.8%; P=0.001) during the morning/day (03:00-15:00) compared with the evening/night (15:00-03:00). No within-day variation in the percentage of MMA was observed. CONCLUSION: The arsenic methylation efficiency of an individual is remarkably stable over time.

Adult↗

Effects of range position, inter-annual variation and density on demographic transition rates of Hornungia petraea populations.

The central-marginal model assumes unfavourable and more variable environmental conditions at the periphery of a species' distribution range to negatively affect demographic transition rates, finally resulting in reduced population sizes and densities. Previous studies on density-dependence as a crucial factor regulating plant population growth have mainly focussed on fecundity and survival. Our objective is to analyse density-dependence in combination with the effect of inter-annual variation and range position on all life stages of an annual plant species, Hornungia petraea, including germination and seed incorporation into the seed bank. As previous studies on H. petraea had revealed a pattern opposite to existing theory with lower population densities at the distribution centre in Italy than at the periphery in Germany, we hypothesised that (1) demographic transition rates are lower, (2) the inter-annual variation in demographic transition rates is higher and (3) the intensity of density-dependence is weaker in Italy than in Germany. To analyse demographic transition rates, we used an autoregressive covariance strategy for repeated measures including density and inter-annual variation. All the three hypotheses were confirmed, but the impact of range position, density-dependence and inter-annual variation differed among the transition steps. All transition rates except fecundity were higher in the German populations than in the Italian populations. Germination rate and incorporation rate into the seed bank were strongly density-dependent. Central populations showed a larger inter-annual variation in fecundity and winter survival rate. Winter survival rate was the only transition step with a stronger density-dependence in peripheral populations. In most cases, these differences between distribution centre and periphery would not have emerged without taking density-dependence and inter-annual variation into account. We conclude that including range position, inter-annual variation and density-dependence in one single statistical model is an important tool for the interpretation of demographic patterns regarding the central-marginal model.

Analysis of Variance↗

Fusion variations of pancreatic ducts in patients with anomalous arrangement of pancreaticobiliary ductal system.

Fusion variations of the pancreatic ducts were studied to elucidate the significance of such variations. We classified structural fusion anomalies of the main and accessory pancreatic ducts on endoscopic retrograde cholangio-pancreatography (ERCP) in 37 patients with anomalous arrangement of the pancreaticobiliary ductal system (AAPB). The fusion variations of the pancreatic ducts were classified into five types: common, ansa pancreatica, branch fusion, looped, and separated. These fusion variations, except for common type, were found in 68% of the 37 patients with AAPB on ERCP. Fusion variations of the pancreatic ducts were very frequent (93%) in the 30 patients with congenital cystic dilatation of the common bile duct (CCD). The branch confluence fashion, in which the terminal bile duct communicated with a pancreatic duct branch, was found only in patients with cystic dilatation cyst of the CCD, and it appeared that cystic dilatation cyst of CCD might differ from spindle or cylindrical cyst originating from embryonic formation of an anomalous confluence. It was also suggested that in patients with fusion variations of the pancreatic ducts, the flow of pancreatic juice might be disordered, leading to the development of acute pancreatitis or pancreatic dysfunction. Consequently, it appears to be necessary to carefully examine patients with AAPB for the presence or absence of any fusion variations of the pancreatic ducts and to observe such patients with long-term monitoring by ERCP, and computed temography, and with pancreatic function tests.

Adult↗

Measurement of the AH and HV interval and His bundle duration: interobserver and intraobserver variation.

Conduction system intervals measured during intracardiac electrophysiologic testing influence clinical decisions. To evaluate measurement reliability, interobserver and intraobserver variation for AH, HV, and His bundle duration measurements from 50 patients were evaluated. The square of the correlation coefficient (r2) was used as the index for measurement reliability. Three investigators performed the measurements. The r2 for interobserver variation of the AH interval ranged from 0.55 to 0.68 and for intraobserver variability from 0.60 to 0.88. The standard error of measurement based on intraobserver measurements ranged from 10.2 to 18.0 ms. The r2 for interobserver variation of the HV interval ranged from 0.42 to 0.63 and for intraobserver variation from 0.489 to 0.73. The standard error of measurement was 6.2 to 9.9 ms. For the His bundle duration, the r2 for interobserver variation ranged from 0.42 to 0.52 and for intraobserver variation from 0.19 to 0.52. The standard error of measurement was 3.1 to 5.2 ms. Although there is measurement variation for AH and HV intervals, their use in conjunction with the history and the surface electrocardiogram to make clinical decisions is appropriate. His bundle duration cannot be measured reliably using the standard recording technique and should not be used for clinical decision making.

Bundle of His↗

Diurnal and other cyclic variations in human fetal heart rate near term.

In 10 healthy women near term, fetal heart rate, as monitored from an abdominal electrocardiogram, and its variation were analyzed over 24 hours. During the daytime, this was combined with real-time scanning for fetal breathing and movements. There was an episodic change in high and low pulse (R-R) interval variation with a mean cycle length of 92 minutes. The changes in cycle length were large; around midnight, episodes of high variation lasted up to 6 hours. Episodes of high variation coincided with greater fetal movement (measured only in daytime). Neither low nor high episodes were consistently related to fetal breathing. Both fetal heart rate and its variability showed a diurnal variation, by 11% and 50%, respectively; these were not statistically related. There was a particularly large change in pulse interval variation with peak values around midnight; concomitantly, there was a diurnal variation in the incidence of accelerations of defined size. The implications of these findings are discussed.

Adult↗

Short-term variation in abnormal antenatal fetal heart rate records.

In a retrospective study the relation of reduced fetal heart rate variation to fetal acidemia was analyzed with a computerized system for numeric analysis. Between 1983 and 1987, 78 pregnancies were identified in which at least one record of the fetal heart rate had very low long-term variation. The outcome was analyzed to determine the numeric criteria of fetal heart rate variation that most efficiently detect a fetus that will die (preterminal) or is dying (terminal). Because fetal compromise was found on occasion to be associated with a slow sinusoidal fetal heart rate rhythm that increased measures of long-term variation. It was necessary to define a new index of short-term fetal heart rate variation (the 1/16 minute epoch-epoch variation). This was closely related to long-term variation (r = 0.9) but provided better detection of preterminal records as judged by metabolic acidemia at delivery or intrauterine death.

Adult↗

Computerized analysis of episodic changes in fetal heart rate variation in early labor.

Fetal heart rate variation in early labor was measured by computerized analysis in cyclic episodes of low or high variation in 136 women at 37 to 42 weeks' gestation. The amplitude (mean +/- SE) in episodes of low variation was 20.6 +/- 0.4 milliseconds; in high variation it was 57.3 +/- 1.1 milliseconds. The duration (mean +/- SE) of low episodes (24.3 +/- 1.3 minutes) was less than that of high episodes (45.1 +/- 2.7 minutes) but was sometimes greater than 1 hour. In episodes of low variation the amplitude was less than 5 beats/min long term in 11% and less than 2.5 milliseconds (pulse intervals) short term in 8%; these measures would be predictive of intrauterine death if persistent before birth. We conclude that the use of decreased fetal heart rate variation as a diagnostic sign of acute fetal hypoxemia in labor is incorrect, because changes of this size occur randomly as a consequence of fetal sleep states. There was no significant correlation between fetal heart rate variation over the last hour of labor and umbilical arterial base deficit on delivery.

Adult↗

Computerized analysis of fetal heart rate variation in postterm pregnancy: prediction of intrapartum fetal distress and fetal acidosis.

OBJECTIVE: Our purpose was to evaluate whether computerized analysis of fetal heart rate variation may improve fetal surveillance in postterm pregnancy. STUDY DESIGN: Three hundred thirty-seven pregnant women who were delivered after 41 weeks' gestation and who had 610 antenatal tests were included in this study. Fetal tests included a nonstress test with a computerized analysis of the fetal heart rate, Doppler examination of the umbilical artery, and a biophysical profile, performed every 2 to 4 days. Induction of labor was performed when the fetal heart rate variation was reduced (< 30 msec), when fetal heart rate decelerations appeared, or when the amniotic fluid index was < or = 5. The results of the fetal surveillance tests were compared with the results of the intrapartum fetal heart rate monitoring and with the metabolic status of the babies at delivery. Sensitivity and specificity of the various tests in predicting intrapartum fetal distress and acidosis at delivery were described by means of the receiver-operator characteristic curve. RESULTS: Ten of 12 fetuses with reduced fetal heart rate variation had a trial of labor. Nine of these 10 fetuses had fetal distress during labor. Seven of the 12 fetuses with reduced fetal heart rate variation were acidotic at delivery (umbilical artery pH < 7.2). Overall, there were 10 acidotic fetuses at delivery in the study group. Only two of them had an umbilical systolic/diastolic ratio > 95th percentile, three had an amniotic fluid index < or = 5, and five had fetal heart rate decelerations before labor. Fetuses who demonstrated an abnormal intrapartum fetal heart rate tracing or who were acidotic at delivery had a significantly higher rate of reduced fetal heart rate variation or decelerations before labor. The largest area under the receiver-operator curve curve for predicting fetal acidosis at delivery or fetal distress during labor was achieved by means of computerized analysis of fetal heart rate variation. CONCLUSION: A computerized numeric analysis of fetal heart rate variation may improve fetal surveillance in postterm pregnancy.

Acidosis↗

Seasonal variation in high density lipoprotein cholesterol.

We investigated the seasonal variation in high density lipoprotein cholesterol (HDL) in 142 dyslipidemic (non-HDL-cholesterol > or = 5.2 mmol/l) middle-aged men in the placebo group of the Helsinki Heart Study over the 5-year trial period. A seasonal pattern was found in HDL fluctuation, with a 4.5% drop during mid-winter (5-year mean 1.192 +/- 0.265 mmol/l) compared with a stable level (5-year mean 1.248 +/- 0.281 mmol/l) during the rest of the year (P < 0.001). A less pronounced seasonal variation in HDL was observed in 85 subjects receiving gemfibrozil. Although affecting pretrial HDL level in cross-sectional analyses, age, alcohol consumption, dietary adherence, physical activity and serum triglycerides had no influence on the seasonality of HDL variation. Smoking had a slight attenuating effect on the variation pattern. Pretrial HDL was influenced by relative weight, but there was also an inverse relationship between HDL and body weight variations, i.e. the annual drop in HDL coincided with the annual peak in body weight. However, seasonal HDL variation was not directly reflected in the annual variation in CHD incidence.

Adult↗

Variations in function and design: testing symmorphosis in the respiratory system.

We explore the question of whether and to what extent the large variation in energy requirements observed among mammals is related to variations in the design of the respiratory system, from the lung to the mitochondria in muscle cells. Resting metabolic rate is determined by body size (allometric variation). Maximal rates of O2 consumption (VO2 max) also vary in a regular manner with body size, but adaptive variation allows some species to achieve much higher values than others of the same body size. We, therefore, consider adaptive variation as modulation of structures and functions above those determined by allometric variation. A model is presented that separates functional and design parameters at four steps of the respiratory cascade: the pulmonary gas exchanger, heart and blood, microvasculature, and mitochondria. The variations observed in these parameters are analyzed with respect to those in energy demand and are discussed in relation to the hypothesis of symmorphosis. We conclude that the design of the internal steps of the respiratory system (mitochondria, capillaries, blood, and heart) is matched to functional demand, whereas the lung maintains a variable excess of morphometric diffusing capacity which may be related to the facts that the lung has limited malleability and that it forms the interface with the environment.

Animals↗

Molecular indicators for palaeoenvironmental change in a Messinian evaporitic sequence (Vena del Gesso, Italy). II: High-resolution variations in abundances and 13C contents of free and sulphur-bound carbon skeletons in a single marl bed.

The extractable organic matter of 10 immature samples from a marl bed of one evaporitic cycle of the Vena del Gesso sediments (Gessoso-solfifera Fm., Messinian, Italy) was analyzed quantitatively for free hydrocarbons and organic sulphur compounds. Nickel boride was used as a desulphurizing agent to recover sulphur-bound lipids from the polar and asphaltene fractions. Carbon isotopic compositions (delta vs PDB) of free hydrocarbons and of S-bound hydrocarbons were also measured. Relationships between these carbon skeletons, precursor biolipids, and the organisms producing them could then be examined. Concentrations of S-bound lipids and free hydrocarbons and their delta values were plotted vs depth in the marl bed and the profiles were interpreted in terms of variations in source organisms, 13 C contents of the carbon source, and environmentally induced changes in isotopic fractionation. The overall range of delta values measured was 24.7%, from -11.6% for a component derived from green sulphur bacteria (Chlorobiaceae) to -36.3% for a lipid derived from purple sulphur bacteria (Chromatiaceae). Deconvolution of mixtures of components deriving from multiple sources (green and purple sulphur bacteria, coccolithophorids, microalgae and higher plants) was sometimes possible because both quantitative and isotopic data were available and because either the free or S-bound pool sometimes appeared to contain material from a single source. Several free n-alkanes and S-bound lipids appeared to be specific products of upper-water-column primary producers (i.e. algae and cyanobacteria). Others derived from anaerobic photoautotrophs and from heterotrophic protozoa (ciliates), which apparently fed partly on Chlorobiaceae. Four groups of n-alkanes produced by algae or cyanobacteria were also recognized based on systematic variations of abundance and isotopic composition with depth. For hydrocarbons probably derived from microalgae, isotopic variations are well correlated with those of total organic carbon. A resistant aliphatic biomacromolecule produced by microalgae is, therefore, probably an important component of the kerogen. These variations reflect changes in the depositional environment and early diagenetic transformations. Changes in the concentrations of S-bound lipids induced by variations in conditions favourable for sulphurization were discriminated from those related to variations in primary producer assemblages. The water column of the lagoonal basin was stratified and photic zone anoxia occurred during the early and middle stages of marl deposition. During the last stage of the marl deposition the stratification collapsed due to a significant shallowing of the water column. Contributions from anaerobic photoautotrophs were apparently associated with variations in depth of the chemocline.

Animals↗

Temporal and spatial variation of RNA content in nymphs of the mayfly, Stenonema femoratum (Say).

Temporal variation of RNA: weight, RNA: protein, RNA: DNA, and protein: DNA ratios in Stenonema femoratum (Say) was assessed by monitoring at the same site in a small midwestern stream over a two-year period. Variation components were estimated using a two-way mixed model analysis of variance with weight class and collection date as main effects. About 30% of the variation in RNA concentration was within-cell variation associated with differences among individuals and analytical error. Temporal variation accounted for about 50% of the total variability in RNA concentration data. RNA: weight had 11% and RNA: protein had 17% variation attributed to weight class effects indicating that these ratios were dependent on the size of the mayfly. RNA: DNA ratios were not influenced by mayfly weight, suggesting that this ratio would be the most appropriate for comparing populations based on means of mixed individual sizes. Comparison of mean RNA: DNA ratios among collection dates yielded significant increases in the ratio during late fall in two consecutive years. Spatial variations in RNA: DNA ratios of S. femoratum collected from sites of similar habitats were not significantly different. These data encourage the future development of RNA concentration as an in situ biochemical indicator of growth rate and possibly of stress related effects on growth rate.

Journal Article↗

Variation in duration of hospital stay between hospitals and between doctors within hospitals.

Whether one examines the average length of hospital stay at the level of geographic areas, at the level of hospitals, or at the level of doctors, length-of-stay figures are known to vary widely. Even for hospital admissions for comparable surgical procedures among comparable groups of patients, significant length-of-stay variations have been reported. As is the case for variations in the occurrence of common surgical procedures, the overall conclusion is that large variations in duration of hospital stay associated with these common surgical procedures are the rule rather than the exception. The objective of the study is to examine whether variations in hospital medical practice, indicated by the duration of hospital stay in this study, can be reduced to differences in practice style between individual doctors within the same institutional setting or to differences in practice style between groups of doctors within the same institutional setting. The latter is assumed to be the combined effect of restrictions on the (hospital) supply side and the predilection of doctors to conform to the practice of immediate colleagues. It was found out that the variation in length of hospital stay, adjusted for patient case-mix, within hospitals is much smaller than the length-of-stay variation between different hospitals. The within hospital variation between (partnership of) doctors is in most of the cases statistically insignificant. Doctors working in more than one hospital on average choose a length of stay close to the average length of stay prevailing in the different hospitals.

Appendectomy↗

A morphometric study and variations on the lumbar arteries of human fetuses.

Lumbar arteries are in series with the posterior intercostal arteries. The aim of this study has been to investigate the morphometric data on the abdominal aorta of the human fetus and define different types of origin variations of the lumbar artery. Initially, the latex solution colored with red ink was injected into the thoracic aorta. The abdominal aorta and its branches were dissected and examined bilaterally in 120 fetuses (ranging between 16 and 32 post-menstrual weeks) and the anatomic variations recorded. Fourteen fetuses with variations were studied and photographed. The origins and morphologic variations of the lumbar arteries were defined and classified. The morphological relationship of the lumbar arteries to the abdominal aorta and the length and width (diameter) of the vessels were investigated by performing measurements using a digital calliper (mm). The frequency and the types of the different variations determined in the present study have been listed. Abdominal aortic branches and Lumbar artery aneurysms are rare lesions with potentially life-threatening consequences and they are difficult to access anatomically and formidable to manage operatively. During the performance of conventional or open surgical replacement of an abdominal aortic aneurysm with prosthetic grafts, the surgeon needs precise knowledge of the anatomy of the abdominal aortic branches and immediate retroperitoneal structures. The variations on the lumbar arteries may have clinical importance. When this region is under diagnostic and/or surgical investigation using computed tomography scan or diagnostic angiography, the possibility of these variations should be take into consideration to avoid complications.

Aorta, Abdominal↗