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The article focuses on the inclusion of the optimal use of blood products in haemovigilance systems (HSs) in the hospitals. It states that questions on HS establishment and how to organize the inclusion of blood products were answered in international forum. C. A. Gonzalez, N. Lena and P. Muntaabski stress that HS limitations should include the control of the use of blood products. M. Lambermont, V. Deneys and D. Sondag say that blood transfusion committee is responsible for blood product use.

The aim of the present study was: (1) to develop a new method for total energy expenditure (TEE) assessment, using accelerometry (ACC) and heart rate (HR) telemetry in combination; (2) to validate the new method against the criterion measure (DLW) and to compare with two of the most common methods, FLEX-HR and ACC alone. In the first part of the study VO2, HR and ACC counts were measured in twenty-seven subjects during walking and running on a treadmill. Considering the advantages and disadvantages of the HR and ACC methods an analysis model was developed, using ACC at intensities of low and medium levels and HR at higher intensities. During periods of inactivity, RMR is used. A formula for determining TEE from ACC, HR and RMR was developed: TEE =1??1??(EQHR??TTHR+EQACC1??TTACC1+EQACC2??TTACC2+RMR??TTRMR). In the validation part of the study a sub-sample of eight subjects wore an accelerometer, HR was logged and TEE was measured for 14d with the DLW method. Analysis of the Bland???Altman plots with 95% CI indicates that there are no significant differences in TEE estimated with HR???ACC and ACC alone compared with TEE measured with DLW. It is concluded that the HR???ACC combination as well as ACC alone has potential as a method for assessment of TEE during free-living activities as compared with DLW [ABSTRACT FROM PUBLISHER]

The objectives of the present study were to study the correlation between the change in serum Fe and Fe absorption when administering 100 mg Fe (as FeSO4) orally, and to study the correlation between the absorption from a 3 mg and a 100 mg Fe (as FeSO4) dose. The study was conducted in a group of eleven male blood donors, without any evident infection, who had given blood 8 weeks before the study. On three consecutive mornings the subjects were served a wheat roll fortified with Fe. On the first 2 d the roll was fortified with 3 mg Fe labelled with 59Fe; on day 3 the roll was fortified with 100 mg Fe labelled with 55Fe. The serum Fe response to the 100 mg dose was followed for 6 h. Fe absorption was measured by whole-body counting. High correlations were seen between the absorption of Fe and the change in serum Fe after 100 mg Fe (r2 0??94, P>0??001), between the absorption from 3 mg and 100 mg Fe (r2 0??88, P>0??001), and between the absorption from 3 mg Fe and change in serum Fe after 100 mg Fe (r2 0??90, P>0??001). This strengthens the evidence that it is possible to use the change in serum Fe as a measure of Fe absorption, e.g. when establishing the relative bioavailability for Fe powders. The results also imply that the induced serum Fe increase following 100 mg Fe added to a food could predict the Fe absorption of a small dose of Fe added to the same meal. [ABSTRACT FROM PUBLISHER]

In several studies oats have been reported to be tolerated by coeliac patients. The aim of the present study was to investigate the nutritional and symptomatic effects of including oats in the gluten-free diet, as well as the patients' subjective experiences. Twenty adult coeliac patients included large amounts of oats in their diet. Food intake, gastrointestinal symptoms, blood samples and body weight were examined and compared with examination at baseline. Diet compliance was checked monthly. The results are based on fifteen patients eating oats for 2 years plus three with only 6-months consumption. The median daily intake of oats was 93 (range 27???137) g/d, and the compliance was good. The mean intakes of Fe and dietary fibre increased (P<0??001) with the oat diet, as well as the intakes of thiamin and Zn (P<0??02). The bioavailability of Fe tended to decrease; this seems not to have influenced the Fe status. Temporary increased flatulence was experienced the first few weeks, as well as improved bowel function with oats in the diet. All patients who carried out the whole study period wanted to continue eating oats after the study, as they found that addition of oats in the gluten-free diet gave more variation, better taste and satiety. Oats improved the nutritional value of the gluten-free diet, had no negative effects on nutritional status and were appreciated by the subjects. Including oats can help coeliac patients following a strict gluten-free diet. [ABSTRACT FROM PUBLISHER]

Determination of methotrexate (MTX) kinetics after an IV bolus (50 mg/m2) allows prediction of the steady-state plasma level of this drug during a constant infusion. This prediction allows high-dose MTX (HD-MTX) therapy without major toxicity. Patients with head and neck carcinoma received HD-MTX and vindesine (VDS) infusions concomitantly. The therapeutic survey of these patients showed that the predicted plasma level of MTX was not achieved in the presence of VDS. Moreover, the computed dose of MTX had to be increased by a larger amount if the MTX plasma clearance after the identification IV push was low (less than 9 l/h). In the presence of VDS, the creatinine clearance is lower than when MTX is infused alone, and MTX renal elimination is identical (MTX or MTX + VDS infusions). Thus it seems that the decrease of the MTX plasma level during MTX-VDS infusion could be due to an increase of cellular incorporation.

Uptake characteristics of Cyclosporine A (CsA), an immunosuppressive agent widely used in organ transplantation, have been evaluated in RAJI cells, a human Burkitt lymphoma cell line which (i) does not bear T-cell markers, (ii) is insensitive to CsA after a 1 hr exposure to concentrations up to 50 micrograms/ml, and (iii) does not metabolize CsA. CsA is rapidly accumulated inside the cells until a near steady-state is achieved (within 1-3 min). This uptake is characterized by two components: one linear process saturable at low drug concentrations (lower than 1 microgram/ml) and another not saturable component even at high drug concentrations (up to 50 micrograms/ml). Uptake of CsA is temperature-dependent and unaffected by the presence of CsD, a structural CsA analog (50 micrograms/ml CsD) or sodium azide (10 mM) in the extracellular compartment. Intracellular accumulation of CsA is associated with the rapid appearance of a cytosolic drug-protein complex, which is responsible at least in part, for the large amount of total drug accumulated inside the cells. Chromatographic analysis of this (3H)CsA-macromolecule complex on a Bio-Gel P-60 exclusion column demonstrates that the molecular weight of this protein(s), likely cyclophilin, is around 15,000-20,000 daltons. Using Lineweaver-Burk analysis of binding equilibrium data, the dissociation constant of CsA for this binding site was approximately 2.2 microM. these studies, which demonstrate that CsA (i) is rapidly accumulated inside the cells as free drug but is also specifically bound to an intracellular macromolecule, and (ii) is selectively retained in the intracellular compartment after the extracellular drug is removed, could explain the intense distribution of CsA in the organs and the slow disappearance of CsA from plasma after CsA therapy in humans.

Population pharmacokinetics of methotrexate (MTX) was evaluated from intravenous test-dose (TD) data (n = 20 corresponding to 174 measured samples). Bayesian prediction of MTX clearance from TD experiments combining population data with measured levels (at times 0.5 and 6 h) was found to be feasible in routine situations with good performance (root mean squared error : rmse (precision) = 1.14 1.h-1 (11.2%) and mean error : me (bias) = 0.06 1.h-1 (NS) relatively to weighted least-square estimates, n = 50). The precision of Bayesian prediction was comparable to that of the model independent which is used in routine practice and involves 9 measured levels over 30 h, (rmse = 1.35 1.h-1 (10.9%), n = 50). However, the routine method presented a significative bias (me = -0.81 1.h-1, n = 50).

The pharmacokinetics of methotrexate and 7-hydroxy-methotrexate were studied in patients undergoing very high-dose methotrexate monotherapy. The patients received, first, two methotrexate intravenous bolus test doses (50 mg/m2) one with and one without concomitant administration of folinic acid (15 mg every 6 h) in a random sequence, and, second, an 8 h infusion, individualized to achieve a peak plasma concentration of 5 X 10(-4) M methotrexate (infusion rates greater than 1000 mg/h). Methotrexate and 7-hydroxy-methotrexate concentrations were measured by specific radioimmunoassays and the data were analysed simultaneously by an integrated pharmacokinetic model. Following test dose administration, methotrexate and 7-hydroxy-methotrexate plasma concentration kinetics were best described by assuming that methotrexate elimination (and 7-hydroxy-methotrexate formation) occurred from a peripheral compartment reaching rapid equilibrium with the plasma. Folinic acid administration did not influence the disposition of either compound. Following the infusion, a significant (P less than 0.01) decrease of methotrexate total plasmatic clearance occurred without modification of 7-hydroxy-methotrexate formation and elimination.

It has been suggested that the intra-erythrocyte levels of methotrexate (MTX) and its polyglutamized derivatives could offer a method for evaluating intracellular MTX accumulation and its metabolism in children with acute lymphoblastic leukemia. We were interested in measuring the intra-erythrocyte levels of MTX in patients with solid tumors receiving high-dose MTX treatment. After a first incorporation stage occurring during infusion, MTX concentrations subsequently increased 9-12 days after the treatment as polyglutamized derivatives. Thirty days after the infusion, MTX and its polyglutamates were still measurable in erythrocytes. The percentage of polyglutamization varied on an individual basis, but two groups of patients could be separated according to their ability to form polyglutamates. We also noted the presence of 7-hydroxy-methotrexate (7-OH-MTX) appearing 48 hours after the beginning of the infusion which was still present in 17/20 samples 30 days after the treatment.

Methotrexate (MTX) and vindesine (VDS) have both been found effective in the treatment of acute leukemia. With regard to their pharmacological effects at the cellular level they can reportedly interact. Administration of MTX at high dose levels has been suggested as both a curative and preventive treatment of blastic meningitis. The purpose of this work was to determine whether an injection of VDS leads to any change in MTX clearance and uptake in the cerebrospinal fluid (CSF). The plasma pharmacokinetic and CSF influx of MTX and VDS were assayed after high dose systemic MTX with an intravenous bolus of VDS administered in the treatment of acute lymphoblastic leukemia. The MTX concentration was determined by enzymatic assay and VDS by radio immunoassay. No interrelation between these drugs was found. MTX levels in the CSF were sufficient for therapeutic effectiveness but were not affected by intravenous VDS. Detectable amounts of VDS were observed in the CSF but were not altered by MTX.

High-dose methotrexate (HD-MTX) infusions associated with vindesine (VDS) have been used in the treatment of head and neck cancer. In a previous study, VDS was shown to increase the apparent plasma clearance of MTX. We have studied the MTX hydroxylation process in the presence of VDS. Different routes of administration have been tested (IV pushes and 24-h or 36-h infusions). A radioimmunoassay has been developed to measure 7-OH-MTX. The defined protocols enabled us to show that VDS influences not only the pharmacokinetic behavior of methotrexate but also its hydroxylation, which is decreased in presence of VDS.

Some of 66 patients with head and neck tumors were treated with high-dose methotrexate monochemotherapy. The use of a prospective mathematical model with pharmacokinetic surveillance proved to be reliable, practical, and useful. By this means chemotherapy could be individualized, with a resultant marked reduction in the frequency and severity of toxicity. The onset of clinical toxic manifestations was significantly correlated with a poor therapeutic response and poor prognosis. The patients were classified in to three groups according to poor, intermediate, and good pharmacokinetic parameters calculated after an intravenous identification dose of methotrexate. These group allocations had a very high prognostic value with regard to toxicity, and especially to the quality of therapeutic response to high-dose methotrexate. They are suggested as useful guidelines in the prescription of high-dose methotrexate chemotherapy.

A preliminary methotrexate (MTX) kinetic evaluation following administration of an IV bolus (test-dose) allowed individualization of high-dose infusions (HD-MTX). This approach combined with therapeutic drug monitoring was found to have good performance over a large scale of predicted steady-state levels (Css) (10(-5) to 10(-4) M over 24 to 36 h) corresponding to 17 to 650 mg/h deliveries (root mean squared error : rmse (precision) = 1.54 X 10(-5) M (21.4%) and mean error : me (bias) = 0.043 X 10(-5) M (NS)). However a significative (p less than 0.05) but rather low over-estimation of dosage (me = 7.38 X 10(-5) M (14.8%)) associated to a decrease in the prediction precision (rmse = 13.3 X 10(-5) M (26.6%)) occurred in 5 X 10(-4) M predicted Css over 8 h (970 to 1970 mg/h deliveries). However in a number of cases (6 out of 29) important deviations from predicted Css occurred, implying the need to stop the infusion before 8 h. These results indicated that MTX pharmacokinetics was linear from low test-dose bolus injections to high-dose infusions. This allowed dosage predictions based upon preliminary estimation of MTX clearance and associated to therapeutic drug monitoring during and following infusion.

Methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) plasma concentration-time curves (AUC) have been analyzed in 24 patients after different routes of MTX administration. After an i.v. bolus (50 mg/m2), the AUC for 7-OH-MTX is correlated with that for MTX and inversely correlated with the MTX plasma clearance. When MTX is administered with plasma steady level standardization, using the test-dose protocol, at a level of 10(-5) M over 36 hr (10(-5), 36 hr), 7-OH-MTX-AUC is still correlated with the i.v. bolus pharmacokinetic parameters. The dose prediction using the classical test-dose protocol provides a less efficient MTX dose adjustment at 5 X 10(-4) M over 8 hr (5.10(-4), 8 hr) and the hydroxylation process is no more correlated with the i.v. parameters. On the opposite, upon 6 successive infusions with 10(-5), 36 hr or 5.10(-4), 8 hr protocols, the plasma concentrations of 7-OH-MTX are not significantly modified. This suggests that the hydroxylation process is not inducible.