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PubMedDate not supplied

[Cytogenetic results of irradiation of Southern Ural residents].

The paper summarizes the results of studies of 85 individuals exposed in the Southern Ural region. The spontaneous frequency of the cells with micronuclei (MN) in a population of human blood lymphocytes after PHA stimulation and cytokinetic block with cytochalasin B has been determined. The sensitivity of lymphocytes to the irradiation at the dose of 1.0 Gy and the adaptive response (AR) after the irradiation at the low adaptive dose of 0.05 Gy, and the challenge dose of 1.0 Gy 5 h later have been studied too. It was shown that the peculiarity of the Urals population consists in a higher individual variability of the frequency of cells with MN in all groups have been investigated (spontaneous, after acute irradiation in the dose 1.0 Gy) in comparison with Moscow people. The proportion of persons with a significant AR in the Urals groups was considerably lower than that identified among Moscow residents, and the number of persons with enhanced radiosensitivity increased following low-dose irradiation. We can suppose that prolonged action of low level radiation with another ecological factors, living in the contaminated regions result in the enhancement of the sensitivity to the genotoxic agents in the separate individuals.

Adult↗
PubMed1999

The relationship between stress and absenteeism.

UNLABELLED: BACKGROUND OF STUDY: Three hundred and sixty three subjects from various civil service organisations were administered the SCOPE-i (Stress, Coping and Personality Inventory) as part of the Institute of Mental Health's efforts to promote mental health in the workplace. AIM OF STUDY: This study examines the relationship between stress-related factors and absenteeism. Absenteeism is measured by the number of days of medical leave taken (MC) and self-report of minor illnesses (MI) which are not severe enough to warrant the coverage of a medical certificate. RESULTS: In this study, we are interested in the differences between MI and MC, and their respective relationships with stress-related factors. We hypothesised that MI, rather than MC, is more related to poor workplace conditions. The findings of this study support this hypothesis. Thus if workplace environment is stressful, people are still likely to come to work despite their illness. An interesting observation in this study is the different ways in which environmental stressors and psychosocial aspects of the workplace environment affect the MC variable. Individuals are more likely to take MC when the environmental stressors are high (i.e., poor lighting, uncomfortable temperatures, etc) as compared to poor psychosocial environmental conditions (e.g., work overload, high organisational tension, career limitations and high personal constraints). On the other hand, when faced with poor psychosocial environmental conditions, MI increases instead of MC. CONCLUSION: These findings have implications on the types of changes in a workplace which employers should make in order to decrease MC and improve physical well-being. In addition, the study shows the usefulness of MI in future studies as a dependent variable.

Absenteeism↗
PubMed1987

[Variability in the levels of carotenoids and vitamin A in the blood serum and milk of cows].

Observations of 20 milk cows of the lowland black and white breed were conducted for 14 successive days in four seasons of the year. The age, lactation stages and efficiency of the animals were different. They were divided into two groups: the first with healthy udders (clinically, bacteriologically, cytologically); the second with secretion disturbances and mastitis subclinical. Blood and milk samples were taken every day during the morning milking. The content of carotenoids and vitamin A was determined by the methods of Carr-Price. Although the same feeding and environment conditions of the animals were maintained, the determined levels of the studied components of both body fluids showed a great variation. Significant differences were found between the mean values calculated for individual cows (individual variability). In the milk of cows from group II, a higher concentration of carotenoids and vitamin A was found. It is proposed to assume a physiological minimum of 30 mcg/100 cm3 for vitamin A and of 100 mcg/100 cm3 respectively for carotenoids in blood serum and 100 mcg/100 cm3 and 5 mcg/100 cm3 respectively in milk.

Animals↗
PubMed1996

Salivary IgA secretion rate in young and elderly persons.

Immunoglobulin A (IgA) is the dominant immunoglobulin isotype on all mucosal surfaces where it acts as a first line of defense against microbial invasion. Recent investigations suggest that secretory IgA (sIgA) concentrations vary over the day due to a range of variables including dietary factors, daily mood, and exercise. In this study, salivary IgA was determined by ELISA in samples of 48 persons grouped as "young" (20-30 years old) and "elderly" (60-80 years old). Unstimulated, stabilized morning and afternoon saliva was collected during 7 consecutive days. Saliva flow, total proteins, sIgA concentrations, and sIgA secretion rates were determined. The main finding was that saliva flow and sIgA secretion rate were significantly lower in the elderly than in the young. Salivary IgA secretion rate was found to be independent of total proteins secreted in all samples. There is individual variability within a particular age group. It was also found that stress and daily events influence the sIgA secretion rate.

Adult↗
PubMed1989

[The effect of acute-phase proteins on inflammation edema due to vaccination].

The authors describe the profiles of a series of acute phase plasma proteins induced by vaccination (VAC) for cholera, typhoid, yellow fever and combinations of these with DTP. Cholera and typhoid VAC as single vaccinations induce the strongest reaction, yellow fever the weakest. The reaction pattern depends also on the kind of vaccination: DTP, especially, raises haptoglobin levels. Great individual variability in reaction exists. The authors also investigated the relation between the levels of these acute phase proteins, including alpha 2-macroglobulin, and the amount of inflammatory oedema that developed at the vaccination site. It was found that the pre-vaccination levels of alpha 2-macroglobulin and haptoglobin were correlated negatively with the oedema developed 24 hrs later, while fibrinogen showed a positive relationship. The acute phase reaction of these proteins did not alter these correlations. The other acute phase proteins had no influence on the oedema in this model. It is concluded that the existing substantial individual differences in plasma levels of alpha 2-macroglobulin, fibrinogen and haptoglobin in part govern the degree of oedema developing after a vaccination; they are to be regarded as factors of the so called 'innate immunity'.

Acute-Phase Proteins↗
PubMed2001

Risk factors for progression of visual field abnormalities in normal-tension glaucoma.

PURPOSE: To uncover risk factors for the highly variable individual rates of progression in cases of untreated normal-tension glaucoma. METHODS: Visual field data were assembled from 160 subjects (160 eyes) enrolled in the collaborative normal-tension glaucoma study during intervals in which the eye under study was not receiving intraocular pressure-lowering treatment during prerandomization and postrandomization intervals. Analyses included multivariate analysis of time-dependent Cox proportional hazard, Kaplan-Meier analysis of "survival" without an increment of visual field worsening, and comparison of slopes of change in mean deviation global index over time. RESULTS: Most migraine occurred in women, but analysis demonstrated that gender and presence of migraine contribute separately to the overall risk. The risk ratio for migraine, adjusted for the other variables was 2.58 (P =.0058), for disk hemorrhage was 2.72 (P =.0036), and for female gender 1.85 (P =.0622). The average fall in the mean deviation index was faster in nonmigrainous women than in nonmigrainous men (P =.05). Suggesting genetic influence, Asians had a slower rate of progression (P =.005), and the few black patients enrolled had a tendency for faster progression. However, self-declared history of family with glaucoma or treated for glaucoma did not affect the rate of progression. Neither age nor the untreated level of intraocular pressure affected the rate of untreated disease progression, despite their known influence on prevalence. CONCLUSIONS: Whereas risk factors for prevalence help select populations within which to screen for glaucoma, the factors that affect the rate of progression help decide the expected prognosis of the individual's untreated disease and thereby the frequency of follow-up and aggressiveness of the therapy to be undertaken.

Aged↗
PubMed1994

Carotenoids, tocopherols, and retinoids in human buccal mucosal cells: intra- and interindividual variability and storage stability.

The baseline, intra-, and interindividual variability as well as storage stability of carotenoids, tocopherols, and retinoids in human buccal mucosal cells were determined because this information is lacking. All the buccal mucosal cell samples were collected after an overnight fast. In the variability study, 154 subjects (median age 57.5 y) provided three samples each at 7-10-d intervals over a 1-mo period. In the stability study, 13 young volunteers provided four samples each before and during the 11 d of oral administration of beta-carotene, alpha-tocopherol, and vegetable juice; the cells were pooled and stored as a pellet at -80 degrees C. Eleven micronutrients were analyzed simultaneously with HPLC. The results indicated that 1) lycopene and beta-carotene were the two major carotenoids, retinol was not detected in most cell samples; 2) the intra-individual variability was small, but the interindividual variability was very large; 3) two measurements of micronutrient concentration in fasting buccal mucosal cells should be adequate to establish a representative baseline for each micronutrient; and 4) the micronutrients under the storage conditions were stable for > or = 8 mo.

Administration, Oral↗
PubMed1994

Portal venous and segmental anatomy of the right hemiliver: observations based on three-dimensional spiral CT renderings.

OBJECTIVE: The purpose of this study was to evaluate the segmental anatomy of the right hemiliver and to assess whether the right hepatic vein and right portal trunk are accurate indicators of the position of the right and transverse scissurae, respectively. SUBJECTS AND METHODS: We examined 26 patients with spiral CT using 5-mm slices, reconstructed at 2-mm intervals. Three-dimensional renderings of the portal and hepatic venous structures were created. The portal ramification pattern and relationship between the hepatic veins and portal system were evaluated. RESULTS: In the right hemiliver, an anterosuperior sector and a posteroinferior sector were present in all patients. In addition, in nine patients, a total of 15 accessory portal sectors were present, each arising directly from the portal bifurcation or the right portal trunk. Further subdivision of the portal sectors showed marked individual variability, with no prevailing branching pattern. The scissura between the anterosuperior and posteroinferior sectors showed an angled orientation--its cranial part was tilted posteriorly (average, 58.4 degrees) and its caudal part was tilted anteriorly (average, 2.8 degrees)--relative to the coronal plane. In 24 patients, portal branches crossed the plane of the right hepatic vein. No transverse scissura could be seen in the anterosuperior or posteroinferior sector. CONCLUSION: The right hemiliver could be divided into anterosuperior and posteroinferior sectors in all patients studied. Many patients have accessory sectors. Further subdivision into portal segments can be described only after the individual portal branching pattern has been studied. The right hepatic vein is an inaccurate indicator of the position of the right scissura. No clear transverse scissura can be seen in the right hemiliver.

Adult↗
PubMed2001

Variability in the cardiac EIT image as a function of electrode position, lung volume and body position.

A study was conducted using the Sheffield electrical impedance tomography (EIT) portable system DAS-01 P to determine the change in the cardiac image with electrode position, lung volume and body position. Sixteen electrodes were positioned in three transverse planes around the thorax at the level of the second intercostal space, at the level of the xiphisternal joint, and midway between upper and lower locations. Data were collected at each electrode level with the breath held at end expiration and after inspiring 0.5, 1 and 1.5 l of air with the subject in both the supine and sitting position. These data were analysed using a Matlab developed program that calculates the average resistivity change in the cardiac region from automatically determined borders. Results show significant individual variability with electrode position and air volume. The middle electrode most consistently shows an increase in impedance in the region of the heart during systole. In some subjects the change in the ventricular-volume-like curve showed a greater than 50% change as a function of lung volume. The pattern of variability with electrode position was not consistent among subjects. In one subject MRI images were obtained to compare actual structures with those seen in the EIT image. The results suggest that using these electrode locations reliable and consistent data, which could be used in clinical applications, cannot be obtained.

Electric Impedance↗
PubMed1987

Formate in urine as a biological indicator of formaldehyde exposure: a review.

The presence of a small amount of endogenously derived formate in human urine is normal; however, formate derived from the metabolism of formaldehyde, several other industrial compounds and some pharmaceuticals may elevate the urine formate concentration above the normally expected values. This elevation in the urine formate concentration presents the possibility of using this as a tool for monitoring exposure to chemicals. Unfortunately, the use of urine formate as a technique for monitoring personal chemical exposure has yet to be evaluated. This review identifies several potentially important variables that could alter the extent to which formate is eliminated through the urine and that could affect the accuracy of using urine formate concentration as an indicator of chemical exposure. Some potentially important confounders that have been identified, but not evaluated adequately, include dietary intake, nutritional status and exposure to cigarette smoke. Furthermore, the metabolism and elimination kinetics have yet to be adequately demonstrated in humans. Without having controlled for potential confounders in previous pharmacokinetic studies, it is unknown whether or not the large range and variation observed in human studies is due to the confounders or to innate individual variability. Given the poor understanding of the normal variation of formate concentration in the urine, the use of it as a biological indicator of chemical exposure becomes questionable. Without appreciable skin penetration, as in this case, the reliance upon air monitoring alone may be more practical. The evidence at this time suggests that the use of urine formate to monitor chemical exposure offers a broad opportunity for investigative research. At the present time, however, the interpretation of urine formate concentration in samples obtained from workers would be difficult.

Animals↗
PubMed2006

ESC study group of sports cardiology position paper on adverse cardiovascular effects of doping in athletes.

The use of doping substances and methods is extensive not only among elite athletes, but also among amateur and recreational athletes. Many types of drugs are used by athletes to enhance performance, to reduce anxiety, to increase muscle mass, to reduce weight or to mask the use of other drugs during testing. However, the abuse of doping substances and methods has been associated with the occurrence of numerous health side-effects. The adverse effects depend on the type of the consumed drug, as well as the amount and duration of intake and the sensitivity of the body, since there is a large inter-individual variability in responses to a drug. Usually the doses used in sports are much higher than those used for therapeutic purposes and the use of several drugs in combination is frequent, leading to higher risk of side-effects. Among biomedical side-effects of doping, the cardiovascular ones are the most deleterious. Myocardial infarction, hyperlipidemia, hypertension, thrombosis, arrythmogenesis, heart failure and sudden cardiac death have been noted following drug abuse. This paper reviews the literature on the adverse cardiovascular effects after abuse of prohibited substances and methods in athletes, aiming to inform physicians, trainers and athletes and to discourage individuals from using drugs during sports.

Adrenergic Agents↗
PubMed2004

Informational masking in hearing-impaired and normal-hearing listeners: sensation level and decision weights.

Informational masking (IM) refers to elevations in signal threshold caused by masker uncertainty. The purpose of this study was to investigate two factors expected to influence IM in hearing-impaired listeners. Masked thresholds for a 2000-Hz signal in the presence of simultaneous multitone maskers were measured in 16 normal-hearing (NH) and 9 hearing-impaired (HI) listeners. The maskers were 70 dB SPL average total power and were comprised of fixed-frequency components between 522 and 8346 Hz that were separated from each other by at least 1/3 oct and from the signal by at least 2/3 octs. Masker uncertainty was manipulated by randomly presenting each masker component with probability p = 0.1,0.2,...,0.9, or 1.0 across different trial blocks. Energetic masking was estimated as the amount of masking for p = 1.0, where masker uncertainty was minimum. IM was estimated as the amount of masking in excess of energetic masking. Decision weights were estimated by a regression of the listener's yes/no responses against the presence or absence of the signal and masker components. The decision weights and sensation levels (SLs) of the stimulus components were incorporated as factors in a model that predicts individual differences in IM based on the level variance (in dB) at the output of independent auditory filters [Lutfi, J. Acoust. Soc. Am. 94, 748-758 (1993)]. The results showed much individual variability in IM for the NH listeners (over 40 dB), but little IM for most HI listeners. When masker components were presented to a group of NH listeners at SLs similar to the HI listeners, IM was also similar to the HI listeners. IM was also similar for both groups when the level per masker component was 10 dB SL. These results suggest that reduced masker SLs for HI listeners decrease IM by effectively reducing masker variance. Weighting efficiencies, computed by comparing each listener's pattern of weights to that of an ideal analytic listener, were a good predictor of individual differences in IM among the NH listeners. For the HI listeners weighting efficiency and IM were unrelated because of the large variation in masker SLs among individual listeners, the small variance in IM, and perhaps because broadened auditory filters in some listeners increased the covariance in auditory filter outputs.

Adult↗
PubMed1992

The effect of a ligament-augmentation device on allograft reconstructions for chronic ruptures of the anterior cruciate ligament.

A prospective study was performed to determine the effect of a combination of a ligament-augmentation device with a bone-patellar ligament-bone allograft for the treatment of chronic rupture of the anterior cruciate ligament. One hundred and fifteen knees in 110 patients were divided into two groups. Group BLB consisted of sixty-six knees in sixty-four patients who were managed with a bone-patellar ligament-bone allograft only, and Group BLB-LAD consisted of forty-nine knees in forty-six patients who were managed with both the allograft and a ligament-augmentation device. Preoperatively, there were no statistically significant differences between the two groups with regard to fifteen variables. All patients were managed with the same postoperative program of immediate motion and rehabilitation of the knee. All patients returned for evaluation at a mean of thirty-four months (range, twenty-three to fifty-three months) postoperatively. The results were evaluated with a comprehensive rating system that assessed twenty factors. Both of these procedures significantly decreased functional limitations and symptoms and improved the level of sports activity and the over-all score. However, the use of the ligament-augmentation device did not improve the efficacy of the reconstruction with regard to any of the individual variables that were assessed or in terms of the over-all score. All but one of the patients regained an arc of 0 to 135 degrees of motion. Although the augmentation device reduced anterior-posterior displacement effectively for the first twenty weeks postoperatively (p less than 0.05), there was no difference between the groups in terms of the percentage of knees that had abnormal displacement at the latest follow-up. A new classification system was developed to determine rates of failure. The over-all rate of failure was 28 per cent (thirty-two) of the 115 knees: 29 per cent (nineteen) of the sixty-six knees in Group BLB and 27 per cent (thirteen) of the forty-nine knees in Group BLB-LAD. The difference between the two groups was not statistically significant. The addition of the ligament-augmentation device did not improve the results of allograft reconstruction in the treatment of chronic rupture of the anterior cruciate ligament. The use of either an allograft alone or an allograft combined with a ligament-augmentation device did not reduce the amount of anterior-posterior displacement satisfactorily in all of the knees.

Adolescent↗
PubMed1997

Pharmacokinetics of oral morphine sulfate in dogs: a comparison of sustained release and conventional formulations.

The pharmacokinetics and bioavailability (F) of single dose sustained release morphine sulfate (OSRMS) and nonsustained release morphine sulfate (NSRMS) were compared to each other and to a bolus injection of morphine sulfate (MS) intravenously (i.v.) in dogs. Beagles (n = 6) were randomly assigned to 3 treatment groups: namely, OSRMS 15 mg orally, NSRMS 15 mg orally, and 15 mg i.v. Serum samples were drawn at intervals up to 480 min following oral and 420 min following i.v. administration. Serum was analysed for morphine concentration using a radioimmunoassay. Data were analysed using non-compartmental pharmacokinetics. The only statistically significant difference between OSRMS and NSRMS was maximum serum concentration (Cmax). There were trends toward longer time to maximum serum concentration (Tmax) and longer mean absorption time (MAT) for OSRMS when compared to NSRMS, but the differences were not statistically significant (P < 0.05). Pharmacokinetic parameters for both oral formulations exhibited large variability in the rate of absorption of MS from the gastrointestinal tract. Bioavailability of both OSRMS and NSRMS was low (15%-17%). As expected, the area under the concentration vs time curve (AUC) and Cmax for the i.v. data was significantly greater than for both oral groups, and Tmax and mean residence time (MRT) were significantly less following i.v. administration. There were no statistically significant differences among the 3 treatment groups for apparent volume of distribution at steady state (Vdss) or elimination parameters. The OSRMS formulation used in this study provided equivalent bioavailability to NSRMS in dogs, accompanied by large individual variability in drug absorption. It also did not appear that the sustained release formulation provided sufficiently prolonged release of morphine sulfate from the tablet matrix in dogs to allow prolonged dosing intervals compared to NSRMS.

Administration, Oral↗
PubMed1995

From controlled drug intake to loss of control: the irreversible development of drug addiction in the rat.

The development of drug taking from controlled intake to drug addiction was studied by means of an animal model. Outbred rats had continuous free access to water and drinking fluids containing different concentrations of a drug for 7-9 months. After an abstinence period of 4-9 months, the drug was offered again (retest). Previous ethological classification of each rat and changes of housing conditions were used to study the modifiability of drug taking. With ethanol and the mu-agonistic opiate etonitazene, two stages followed each other. Controlled drug intake was adjusted to situational and individual variables. Social isolation of the rats raised the intake of ethanol and opiate. Dominant rats took less drugs than subordinate ones, but, in contrast to the latter, increased drug consumption after social disturbances. The adjustment of drug taking to social variables, was accompanied by changes in the dopaminergic and GABAA-ergic neurotransmission and by altered responses to acute drug administrations. Further, place preference, associated with reinforcing stimuli was modulated by subchronic sensitization/desensitization of dopaminergic transmission. Controlled drug intake lasted for 6-8 months, after which a spontaneous increase of drug consumption was found which latently continued during abstinence periods of 1 month. In the retest after abstinence, drug intake of these rats was strongly increased compared with both their previous consumption and that of drug-naive controls. Since drug taking could no longer be modulated by gustatory, environmental or individual factors (loss of control), it was considered as addictive. Addiction appeared to be specific to the kind of the drug. It persisted for the rest of the rat's life. After long periods of abstinence, ethanol-addicted rats revealed a completely altered pattern of response to self-administered alcohol compared with controlled drinkers. Their dopaminergic D1-transmission was irreversibly altered. Drug addiction only developed when the rat had free choice between water and drug-containing solutions. Long-term forced administration of ethanol or opiate, only led to physical dependence bot not to addiction. Some applications of the animal model are discussed, concerning the assessment of risk factors, the intake of drug combinations, residual neurochemical changes and concepts of treatment.

Animals↗
PubMed1990

Five-year reproducibility of natural head posture: a longitudinal study.

Natural head posture (NHP) is being increasingly used as the logical reference position for the evaluation of craniofacial morphology. The basic premise underlying its use is that the long-term clinical reproducibility (variability) of NHP is significantly less than the variability of conventional intracranial reference planes with respect to the vertical. This study reports the results of a 5-year longitudinal study evaluating the reproducibility over time of NHP lateral cephalometric radiographs. The subjects were 126 randomly selected Chinese children in Hong Kong who were first assessed at the age of 12 years. Thirty subjects were recorded after 5 years. NHP reproducibility deteriorated over time but showed signs of stabilizing after 1 to 1 1/2 years. The method error was 1.93 degrees after 1 to 2 hours, 2.34 degrees after 3 to 6 months, and 3.04 degrees after 5 years. The individual variability of NHP reproducibility also increased over time. The standard deviation of the SN/vertical angulation was 2.61 degrees after 1 to 2 hours, 3.16 degrees after 3 to 6 months, and 4.20 degrees after 5 years. Further longitudinal data are required to determine whether NHP reproducibility continues to deteriorate after 5 years. After 5 years, however, the variance of NHP (9.24 degrees [= 3.04(2)]) remains significantly less than the variance of intracranial reference planes to the vertical (25 degrees to 36 degrees).

Cephalometry↗
PubMed1989

Pharmacokinetics and effects on exercise heart rate of PK 11195 (52028 RP), an antagonist of peripheral benzodiazepine receptors, in healthy volunteers.

PK 11195 (or 52028 RP; 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide), an antagonist of the peripheral-type benzodiazepine receptors which are coupled to calcium channels, was administered to 10 healthy volunteers in order to study the pharmacokinetics and cardiovascular effects of the drug. PK 11195 was randomly administered intravenously (10 mg) and orally in three single dosages (100, 200 and 400 mg). Placebo was only given orally. Heart rate and blood pressure were recorded at rest and during exercise tests which were performed at 0, 1, 3, 6 and 24 h after dosing on each study day. The results showed that after IV administration, PK 11195 was rapidly distributed in two or three open compartments. Its elimination T 1/2 was short (3.7 +/- 3.0 h) with high interindividual variability. After oral ingestion the pharmacokinetics of PK 11195 were linear over the range of 100-400 mg single oral doses with a stable absolute bioavailability (33%). T 1/2 elimination was prolonged (7-12 h) and the presence of secondary increases in plasma concentration at 8-10 h and 22-24 h after drug absorption may have been related to enterohepatic cycling. No unchanged PK 11195 could be detected in urine. PK 11195 did not significantly modify heart rate and blood pressure at rest or during exercise and was well tolerated by the subjects. These data suggest a high inter-individual variability in PK 11195 disposition with extensive metabolism in normal exercising volunteers.

Administration, Oral↗
PubMed1999

Prediction of methotrexate elimination after high dose infusion in children with acute lymphoblastic leukaemia using a population pharmacokinetic approach.

High-dose methotrexate (HD-MTX) with leucovorin rescue is a component of therapy in children with acute lymphoblastic leukaemia. Since MTX toxicity is related to drug exposure, a monitoring of serum MTX concentrations at H24, H48, H72 and until the concentration is less than 0.2 micromol/L is commonly performed. However, a number of patients may reach concentrations of less than 0.2 micromol/L long before the next sampling is scheduled. The aim of our study was to develop a Bayesian method predicting the time at which MTX concentration reaches 0.2 micromol/L in order to decrease the number of samples drawn and to allow for a more rapid patient discharge. Methotrexate population parameters were estimated from a retrospective analysis of 60 infusions in 23 children and MTX concentrations were predicted from an independent set of 20 courses in 14 children with a Bayesian approach using either one (H48) or two (H24 and H48) samples. The following population parameters were obtained using a two-compartment model: CL = 3.51 L/h (inter-individual variability: 66%), Vd = 8.67 L (58%), k12 = 0.0044 h(-1)(105%), k21 = 0.039 h(-1)(25%). Clearance and Vd were found to increase with weight and age respectively. Both sampling schedules tested for the Bayesian estimation enabled accurate prediction of concentrations and provided satisfactory precision despite a small bias. When considering the ability to predict the time at which the threshold was reached, the one-sample (H48) schedule gave the best results. We conclude that a sampling schedule involving only one sample and Bayesian parameter estimation may be able to predict the delay necessary to reach 0.2 micromol/L in each individual.

Adolescent↗