Fasting plasma carotenoids concentrations in Crohn's and pancreatic cancer patients compared to control subjects.

Carotenoids are colored molecules that are widespread in the plant kingdom, but animals cannot synthesize them. Carotenes are long, apolar molecules which require fully functioning digestive processes to be absorbed properly. Hence they could be interesting markers of intestinal absorption and digestion. Indeed, only few tests are available to assess these processes and only the D-xylose tolerance test is routinely used. However D-xylose is a sugar that tests only the absorption of water-soluble compounds and it only tests duodenal absorption. In this study, we have evaluated carotenoids as markers of digestion and absorption. We compared fasting plasma carotenoids concentrations in 21 control subjects, 20 patients with Crohn's disease, and 18 patients with pancreatic cancer. Crohn's disease alters intestinal absorption while pancreatic cancer decreases pancreatic enzyme secretion thus impairing digestion. Results show that all carotenoids are significantly lower in Crohn's and cancer patients as compared to control subjects and the multifactorial analysis shows that this decrease is mostly independent of dietary intake. Interestingly, maldigestion as seen in pancreatic cancer more strongly influences plasma lutein and lycopene concentrations while malabsorption in Crohn's disease acts on other carotenoids. Thus carotenoids could be interesting alternatives for testing and following patients that are suspected of having malabsorption or maldigestion syndromes.

[Recent knowledge about intestinal absorption and cleavage of carotenoids]. / Données récentes sur l'absorption et le catabolisme des caroténoïdes.

Our knowledge about intestinal absorption and cleavage of carotenoids has rapidly grown during the last years. New facts about carotenoid absorption have emerged while some controversies about cleavage are close to end. The knowledge of the absorption and conversion processes is indispensable to understand and interpret the perturbations that can occur in the metabolism of carotenoids and vitamin A. Recently, it has been shown that the absorption of certain carotenoids is not passive - as believed for a long time - but is a facilitated process that requires, at least for lutein, the class B-type 1 scavenger receptor (SR-B1). Various epidemiological and clinical studies have shown wide variations in carotenoid absorption from one subject to another, such differences are now explained by the structure of the concerned carotenoid, by the nature of the food that is absorbed with the carotenoid, by diverse exogenous factors like the intake of medicines or interfering components, by diet factors, by genetic factors, and by the nutritional status of the subject. Recently, the precise mechanism of beta-carotene cleavage by betabeta-carotene 15,15' monooxygenase (EC 1.14.99.36) - formerly called beta-carotene 15,15' dioxygenase (ex EC 1.13.11.21) - has been discovered, and a second enzyme which cleaves asymmetrically the beta-carotene molecule has been found. beta-carotene 15,15' monooxygenase only acts on the 15,15' bond, thus forming two molecules of retinal from one molecule of beta-carotene by central cleavage. Even though the betabeta-carotene 15,15' monooxygenase is much more active on the beta-carotene molecule, a study has shown that it can act on all carotenoids. Searchers now agree that other enzymes that can catalyse an eccentric cleavage of carotenoids probably exist, but under physiological conditions the betabeta-carotene 15,15' monooxygenase is by far the most active, and it is mainly effective in the small bowel mucosa and in the liver. However the conversion of provitamin A carotenoids into vitamin A is only partial, and requires a satisfactory protein status.

[Urinary cotinine and nicotine metabolites measurement]. / Dosage urinaire de la cotinine et des métabolites de la nicotine.

UNLABELLED: According to the recent regulations (Circulaire DGS/DH du 3 avril 2000), tobacco dependence must be determined by the measurement of urine nicotine metabolites. Various assay methods are presently available. They were tested in order to evaluate their analytical performances and to determine how they can be used for the clinical management of smoking cessation. MATERIAL AND METHODS: Urine samples from a single void (n = 97) were obtained from active and abstinent smokers (with or without nicotine substitutive therapy). They were all analyzed by the various methods. Cotinine concentration was measured in six laboratories, using HPLC combined with UV detection according to a standardized procedure (Ann Biol Clin 2002 : 60 : 263-72). Immunoassay methods were also tested and the values obtained from urine samples were compared to urine cotinine measured by HPLC-UV. RESULTS: HPLC-UV: Urinary cotinine varied in a range from undetectable to 4 mg/L. An interlaboratory comparison was performed according to the Valtec procedure (calculation of equation of Deming, chart of differences). There was a good accordance between laboratories. Cotinine concentration was only slightly influenced by fluid intake, as shown by a poorly significant correlation between cotinine and creatinine (r = 0.23, p = 0.05). Homogeneous immunoassays: The two homogeneous immunoassays (Cotinine) from Thermo Electron and Cotinine Enzyme Immunoassay commercialized by Microgenics were highly correlated (r = 0.97). The correlation was not so strong with HPLC-UV (r = 0.86). Firstly, values were found higher with immunoassays because antibodies crossreact with 3-hydroxycotinine. Secondly, the ratio of immunoassays values to HPLC-UV values varied according to urine specimens. Finally, there was a highly significant correlation with urine creatinine (r = 0.40, p = 0.0001), thus indicating the influence of fluid intake. Heterogeneous immunoassay: The kit Metabolites of Nicotine commercialized by DPC France was tested on the analyzer Immulite, using a procedure specifically established for urine. Antibodies revealed a large spectrum of nicotine metabolites. Therefore, the values were much higher than those observed for the same urine samples with homogeneous immunoassays. CONCLUSION: HPLC-UV can be recommended for the measurement of urinary cotinine, as it was shown a good accordance between laboratories. The low detection limit is of interest for the diagnosis of Environmental Tobacco Smoking. Homogeneous immunoassays can be easily used for routine analysis as they can be performed directly on urine specimen. The results must be interpreted according to cut-off values specifically established according to homogeneous or heterogeneous immunoassays. Variability induced by fluid intake must be taken into account. The interest of the heterogeneous immunoassay needs to be confirmed for the diagnosis of Environmental Tobacco Smoking.

[Measurement of urinary free cotinine. Comparison with the level of expired air carbon monoxide]. / Dosage de la cotinine urinaire libre. Deuxième partie: comparaison avec le taux de monoxyde de carbone dans l'air expiré.

BACKGROUND AND AIM: Cotinine is a very reliable index for the estimation of active or passive smoking. Sampling from a single urine void is well accepted by smokers who are willing to stop. It is not possible to exclude modification of urine cotinine according to beverage intake. The aim of this study was to determine if urine cotinine concentration must necessarily be adjusted to creatinine or not, by making comparison with expired air carbon monoxide. MATERIAL AND METHODS: Carbon monoxide was measured in 53 smokers coming for the first time in a smoking cessation program. Urine cotinine was measured by HPLC-UV. The cut-off value for abstinence is 8ppm and 0.05 mg/L, repectively. Urine creatinine was determined using the Jaffe reaction. RESULTS: Mean CO level was 18.5 +/- 10.6 ppm and mean urine cotine was 1.45 +/- 0.86 mg/L. Eight smokers had CO 8 ppm. They should be considered as abstinent. However, only one of them had a cotinine under the detection limit. Urine creatinine varied in a large range (0.7 - 35 mmol/L). But, cotinine was only weakly correlated to creatinine (r = 0.279, p = 0.037). There was a highly significant correlation between cotinine and CO (0.649, p = 0.0001). The correlation of cotinine/creatinine versus CO was not significant (r = 0.249, p = 0.072). In order to take into account fluid intake, urine cotinine of each sample was adjusted as if creatinine was equal to the mean (8.3 mmol/L) of the group of subjects. The correlation observed with adjusted or non adjusted cotinine and CO (r = 0.640, p < 0.0001) was the same. CONCLUSION: Urine cotinine from a single void is an accurate index of tobacco smoking at the individual level. There is no need to adjust cotinine concentration, taking into account urine creatinine. Measurement of urine cotinine can be useful to manage smokers who deliberately wish to overcome tobacco dependence, offering the opportunity to provide an adequate level of nicotine substitutive therapy. It is also of peculiar importance to follow-up pregnant women and smokers for whom cessation is required after a clinical event. Finally, absence of cotinine in urine can be used to document abstinence from tobacco products.

Obesity and iron status in menstruating women.

The relationship between iron stores and obesity in menstruating women was studied in 20 obese and 20 nonobese women matched for age and contraception. Although no difference was observed in serum iron or total-iron-binding capacity, the obese group showed significantly higher hemoglobin (137 +/- 9 vs 10 g/L, mean +/- SD; P less than 0.01), hematocrit (0.41 +/- 0.02 vs 0.39 +/- 0.03, P less than 0.05), and serum ferritin concentrations (48.0 +/- 44.3 vs 25.8 +/- 19.5 micrograms/L, P less than 0.05). There was no difference between obese and nonobese women in either the menstrual-cycle interval or the duration of the menstrual flow. Iron intake was significantly higher in the obese group (15.9 +/- 2.9 vs 14.1 +/- 2.9 mg/d, P less than 0.05). These results suggest that obese menstruating women are at low risk of depleting iron stores, possibly because of high iron intake. Iron-fortification programs might thus be undesirable in such subjects.

[Quality control of capillary blood measurements in clinical services: follow up by the biologist]. / Contrôle de qualité des analyseurs de glycémie capillaire dans les services hospitaliers: suivi par le biologiste.

In Bichat-Claude Bernard Hospital, the study of capillary glucose analyzers in the aim of uniformizing the selection of glucose meters, has shown the relevance of a standardized handling in order to obtain clinically interpretable results. It has been necessary to implement a quality follow up by the biologist. In the first stage, the biochemistry laboratory, with the clinical service supervisor and the supplier, has assured the training of the medical staff habilitated to use the meters and to carry out a quality control. In the second stage, the biologist implemented a monthly control on a total blood control sample, the stability of which has been checked after the necessary addition of glucose. Dosing of that sample, which is used as an external control, is carried out in parallel by the QID Precision glucose analyzer (Abbott) and by the portable Hemocue B Glucose (Vermed), which is selected as a comparison standard. This allows a monthly control of the accuracy of the meter. The condition of the equipment, as well as the weekly control follow up, validated by the nurse, is registered on a sheet prepared by the biologist. In partnership with Vermed, we have developed a processing software of the data stored in the Hemocue, allowing the automatic issue of a report summarizing the equipment condition and the data of weekly and monthly controls follow up. This report, signed by the biologist, is sent to every Service Manager and Supervising Nurse. On the basis of our one year experience, this practice has generated an efficient collaboration between the clinical services and the biochemistry laboratory, allowing to keep the quality of the capillary glucose measurements performed in inpatients.

Beta 2-microglobulin in liver cirrhosis: study of a local synthesis in ascitic fluid.

Beta 2-microglobulin determinations in ascitic fluid (A) and serum (S) collected on the same day, were performed in 24 patients suffering from alcoholic liver cirrhosis. Ascitic beta 2-m concentration varied from 0.4 to 4.6 mg/l for patients with a normal renal function. Much higher values were found in patients with chronic renal failure. No correlation could be established between ascitic beta 2-m level and the clinical evolution of the cirrhosis. Comparative measurements of beta 2-m S/A ratio and albumin, transferrin, total protein S/A ratios suggests a local synthesis of beta 2-m in ascitic fluid. This is confirmed by an immuno-cytochemical technique which reveals the localisation of beta 2-m in the cytoplasm of peritoneal cells. The presence of beta 2-m in ascitic fluid seems to be related to an ultrafiltration across the peritoneal membrane as well as a local polyclonal activation of the immune system.

Study of carbohydrate material isolated from ultrafiltrates in patients with chronic renal failure.

We have isolated substances of molecular weight ranging between 350 and 2,000 daltons from ultrafiltrates of 3 patients treated by maintenance haemodialysis for chronic renal failure. Such substances might have a role in the genesis of uraemic toxicity. We have chiefly studied their carbohydrate content. Material was fractionated according to a procedure previously used to urine in healthy controls. Consecutive ion exchange, charcoal Celite and paper chromatography lead to the isolation and purification of oligosaccharides, glycopeptides, glucuronoconjugates and peptides. The different classes of carbohydrate material present in dialysis fluids from uraemic patients are close to those formed in normal urines. All the oligosaccharides in renal failure urine had have identified in normal urine. In a previous studies we have demonstrated that the levels of glucuronoconjugates are higher in the blood of uraemic patients. The glucuronoconjugates and their aglycones could have a toxic effect but a great part of them is removed by hemodialysis.

Glutamate-arginine salts and hormonal responses to exercise.

Hormonal changes during exercise is of growing interest because of their role in adaptation, and performance. The production of amino acids (AA) due to the degradation of muscle protein increases during exercise and some AA may be utilized for energy expenditure or as hormonal secretagogues. Thus, one can propose a strategy to reduce muscle protein breakdown and regulate hormones involved in energy metabolism by dietary AA supplementation. We assessed the effects of glutamate-arginine salt (AGs) ingestion on exercise-induced hormonal alterations in highly trained cyclists (age 18-22 yrs). Using an indwelling catheter, we collected multiple blood samples at rest, during warm up, during and after an intense exercise session. Plasma growth hormone (hGH), insulin and cortisol were measured by radioimmunoassay. As reported in previous studies, we observed a marked increase in plasma hGH and cortisol levels during and after exercise in the placebo (Pl) condition as well as a slight decrease in insulin concentration. In addition, we found that the ingestion of AGs had significant effects on some dynamic hormonal changes. AGs had no effect on resting plasma levels of hGH, insulin or cortisol. However, the marked elevation in cortisol and hGH during and after exercise in the placebo condition, was greatly diminished when subjects ingested AGs. Our results show that AGs can modify exercise-induced hormonal changes and raise the possibility that it may be used to alter energy metabolism during endurance exercise.

[Factors of gastroesophageal acid reflux in severe obesity]. / Facteurs de reflux gastro-oesophagien acide dans l'obésité sévère.

OBJECTIVE: To study in morbid obesity the relationship between the degree of gastro-oesophageal reflux (GER) and the excess of body weight, or the related factors such as the energy intake or the fat distribution (waist-hip ratio). METHODS: In 20 morbid obese subjects (body weight: 125 +/- 32 kg) consulting in a weight-loss programme, anthropometric measurements, 3-hr oesophageal pHmetry, double isotope labelled meal for studying gastric emptying, study of gastric acid and pepsin secretions using PEG 4,000 as marker, and upper endoscopy were performed. RESULTS: Nine out of the 20 patients had more than 10 GER per 3-hr period. Seven patients had at least one GER symptom per day. In 6 patients, pH was under 4 for more than 10% of the time. The total number of GER and the number of GER of more than 5 min duration were correlated to the body mass index (P = 0.016 and P < 0.05 respectively). The number of GER was also correlated to the android type of overweight (P < 0.03). These relationships persisted when sex, age, smoking, and obesity complications (such as diabetes) were taken into account. There was a positive correlation between the number of GER and energy and lipid intake (energy intake: 3,119 +/- 1,082 kcal/day; P < 0.003 for both). The degree of GER was positively related to basal acid output (P = 0.049), and to sham feeding-stimulated acid output (P = 0.05); it was negatively related to gastric emptying half time, but was not correlated with basal or stimulated pepsin output. A relationship was found between body mass index (BMI) and gastric emptying half time for solid (P = 0.002) and liquid phases (P = 0.001). CONCLUSION: GER seems to be common in long lasting morbid obesity. The number of refluxes increased with waist/hip ratio, BMI and energy or fat intake. GER was also increased by decreased gastric emptying rate, which was in part determined by BMI. The real prevalence of GER in morbid obeses must be determined by a large prospective study.

Evaluation of the Technicon Dax 48: a multiparametric biochemical analyzer.

The Technicon Dax 48 system is a random access, selective, multitest, open reagent autoanalyzer with a capability of performing up to 34 analytes (32 colorimetric + two ISE). The Technicon Dax 48 has been evaluated over a 3-month period. Twenty-one blood parameters and seven urinary parameters have been studied including substrates, enzymes and electrolytes, according to the 'Valtec' protocol from the French Society for Clinical Biology (SFBC). Comparison for accuracy was done with results from our routine analyzer. Praticability has been evaluated by methodology adaptation and effective throughput checking. Quality for spectrophotometer and temperature control is in agreement with required criteria. The overall design of the system, one sample, one flow cell, one reagent line and nozzle, one specific hydraulic circuit per analytical method, avoids, de facto, any contamination. Result analysis and interpretation show excellent analytical performance (precision, accuracy, analytical range). For the evaluated methods, 85% of the coefficients of variation are under 2%. Sample sizes of 500-microliters are hardly compatible with pediatric samples. There are many advantages when using Dax 48: blood and urine samples can be accommodated at random and the superior quality of electrodes guarantees 20,000 tests. Automated procedures for start up, shut down, maintenance and an effective throughput 1.5 higher than our current routine analyzer's (comparison system) makes Dax 48 more appropriate to handle a large workload. User-friendly software, ease of use and analytical performances make the Dax 48 system suitable for institutions with a large workload.

[Course of the concentration of serum free amino acids as a function of time and the method of preservation]. / Evolution de la concentration des acides aminés libres du sérum en fonction du temps et du mode de conservation.

In order to determine the optimal conditions for storage in the case of deferred serum amino acid assay, the authors studied the effect of storing the sample for four hours at two different temperatures: melting ice and ambient temperature, as well as the effect of storing the amino acids for three months according to four methods of storage; freezing at -20 degrees C and -80 degrees C of deproteinised and non-deproteinised serum. When the analysis was performed within four hours of collection of the specimen, the best conditions are obtained when the sample is kept at the temperature of melting ice. The optimal conservation consists of immediately deproteinising the sample and storing it frozen for 14 days.

[Stability of alpha-tocopherol: pre-analytical conditions in its determination in blood samples]. / Stabilité de l'alpha-tocophérol: conditions préanalytiques à son dosage dans les prélèvements sanguins.

Incomplete and controversial data exist concerning vitamin E or alpha-tocopherol stability in biological samples. Recent clinical interest in the protective function of alpha-tocopherol provided another reason for the setting-up of a multicenter study by the Sociéte Française de Biologie Clinique. Our purpose was to examine the effects on alpha-tocopherol stability, firstly, of collection and transportation of blood samples, and, secondly, of the temperature (-20 degrees C and -80 degrees C) and period of storage of serum or plasma. alpha-tocopherol was determined in serum or plasma by isocratic liquid chromatography with UV detection at 292 nm. Our results established that alpha-tocopherol was extremely stable in blood, serum or plasma over 8 hours without special handling conditions (light, temperature). Pools of serum or plasma were stable for at least 3 months at -20 degrees C and -80 degrees C. They are suitable for use in the quality control of alpha-tocopherol. On the other hand, in some samples, we observed great variability in the rate of alpha-tocopherol degradation. However, there was lesser degradation when these plasma samples were stored at -80 degrees C instead of -20 degrees C. We therefore do not advise storing serum or plasma for more than 1 month at -20 degrees C for more than 3 months at -80 degrees C. This latter temperature is recommended in epidemiological studies.

[Measurement of carotenoids by high pressure liquid chromatography: from difficulties to solutions]. / Dosage des caroténoïdes par chromatographie liquide haute performance: des difficultés aux solutions.

The measurement of serum carotenoids by HPLC has been largely improved during the last 10 years. However these techniques still require much time and skills, and direct application of published methods is rarely satisfying. We report here the difficulties that we met to transfer some HPLC methods described in the literature to our laboratories. We propose some solution to overcome the problems that we have encountered, our experience will perhaps help out other biologists. We reported also some results obtained in healthy populations.

[Determination of serum or plasma alpha-tocopherol by high performance liquid chromatography: optimization of operative models]. / Dosage de l'alpha-tocophérol sérique ou plasmatique par chromatographie liquide haute performance: optimisation du mode opératoire.

A previous multicentric study set up by the Société française de biologie clinique has emphasized the usefulness of a standardized procedure for the determination by high performance liquid chromatography of alpha-tocopherol in serum or plasma. In our study, we have tested every step of the different published procedures: internal standard adduct, lipoprotein denaturation and vitamin extraction. Reproducibility of results was improved by the use of tocol as an internal standard when compared to retinol or alpha-tocopherol acetates. Lipoprotein denaturation was more efficient with ethanol addition than with methanol and when the ethanol/water ratio was > or = 0.7. Use of n-hexane or n-heptane gave the same recovery of alpha-tocopherol. When organic solvent/water ratio was > or = 1, n-hexane enabled to efficiently extract, in a one-step procedure, the alpha-tocopherol from both normo and hyperlipidemic sera. Performances of the selected procedure were: detection limit: 0.5 microM--linear range: 750 microM--within run coefficient of variation: 2.03%--day to day: 4.76%. Finally, this pluricentric study allows us to propose an optimised procedure for the determination of alpha-tocopherol in serum or plasma.

[Recommendations for the installation in the laboratory of metrological functions and corresponding documentation (Document B)]. / Recommandations pour l'installation dans le laboratoire de la fonction métrologie et de la documentation correspondante (Document B).

In order to ensure the quality of analytical results, clinical laboratories shall have a perfect control of process and equipments of measurement. Therefore is recommended individualisation of metrological function, generally entrusted the quality manager. This quality manager will draw up a metrological traceability, verifications and confirmations, control of non conformities, follow-up and evaluation of metrological function.

[Carotenoids: 1. Metabolism and physiology]. / Les caroténoïdes: I. Métabolisme et physiologie.

Carotenoids are a family of pigments with at least 600 members. They derive from lycopene after steps of cyclisation, dehydrogenation and oxidation. It is their chemical structure that determines their physiochemical properties and, in part, their biological activities. About 50 carotenoids can be found in human diet and about 20 of them have been found in plasma and tissues. There is no RDA (Recommended Daily Allowance) for carotenoids. Quantities of carotenoids in diet are difficult to estimate, partly because methods used for the establishment of food composition tables were not specific and sensitive enough. Also, given values do not always take into account variations due to season and region of culture. Absorption of beta-carotene in humans has been the subject of numerous studies but only very little is known about other carotenoids. In general, absorption depends on bioavailability from the food matrix and solubility in micelles. After absorption through passive diffusion, carotenoids follow the chylomicrons metabolism. They are taken up by the liver and released in the blood stream in lipoproteins (VLDL). Carotenoids with no-substituted beta-ionone cycles (alpha and beta-carotene and beta-cryptoxanthin) have provitamin A activity. Highest activity has been found for all-trans beta-carotene. Not all steps of vitamin A biosynthesis and metabolism of other carotenoids have been clarified yet. Besides their provitamin A activity, carotenoids have numerous biological functions. They are efficient scavengers of free radicals, particularly of 1O2. In vitro they have been shown to protect LDL. However, results in vivo are inconsistent. Other functions include enhancement of gap junctions, immunomodulation and regulation of enzyme activity involved in carcinogenesis.

[Presentation for the use of a clinical laboratories of standards of metrology (Document A)]. / Présentation, à l'usage des laboratoires d'analyses de biologie médicale, des normes de métrologie (Document A).

Clinical laboratories shall have a perfect control of "in vitro diagnostic medical devices" to ensure the quality of their analytical results. This introductory presentation to a serie of documents of recommendations tackles the different standards of metrology concerning the requirements to reference materials, metrological traceability, metrological confirmation, management of measurement as well as uncertainty of measurement. The standards concerning clinical laboratories are then succinctly described.

[Biomarkers of tobacco smoke exposure]. / Les marqueurs spécifiques du tabagisme.

Tobacco smoking is a major risk factor for cancer, cardiovascular diseases and respiratory illnesses. Smoking is increasing among children and adolescents with subsequent consequences on the health. Furthermore, maternal tobacco smoking during pregnancy adversely affects prenatal growth. Nicotine, the most important tobacco alkaloid, is responsible for maintaining tobacco addiction. According to a recent Circulaire de la direction générale de la santé, nicotine dependence should be determined through questionnaires and quantitative estimate of nicotine metabolites. Nicotine blood level fluctuates and urinary nicotine excretion is of short duration. Nicotine is intensively metabolized in the liver and oxidized into cotinine. Urinary measurement of cotinine appears to be highly related with the degree of intoxication and to allow the differentiation between non exposed and exposed non-smokers. In order to check the present application of nicotine metabolites measurement, a survey was conducted in 340 smoking cessation units. Forty percent physicians (n = 137) answered the survey. For 17% of them, the quantification of nicotine metabolites is included in their daily practise and for 79%, guidelines about cotinine measurement should be given in France. Sixty-seven biologists answered the survey. Recommendations for immunoassay and HPLC determination of cotinine should be given as reported by 66 and 44% of them respectively. Indeed, urinary cotinine measurement with high performance liquid chromatography is highly sensitive and specific. However, immunoassays are more convenient. These two approaches are presently under investigation in order to provide guidelines for optimal use in various clinical situations. Traditional measures for nicotine dependence are the number of cigarettes smoked per day, nicotine intake expressed as mg per day, Fagerstr m questionnaire, expired air carbon monoxide, thiocyanates and cotinine levels in biological fluids. Urinary cotinine measurement is the most useful for the follow-up of smoking cessation including adjustment of nicotine replacement therapy, especially after a clinical event or for the follow-up of smoking pregnant women. It allows the detection of passive smoke exposure in children who are hospitalized for recurrent respiratory illnesses.

[Renal clearance technic for individualizing lithium dosage in routine hospital care]. / La méthode de la clairance rénale pour l'individualisation des posologies du lithium en routine hospitalière.

Lithium has a narrow therapeutic index and exhibits a wide pharmacokinetic variability. Individual dosage regimen adjustment is necessary to warrant the efficacy and safety of long-term treatment. We propose the "renal clearance method" for rapid determination of the lithium carbonate daily dose for chronic therapy. After the first intake of drug by a manic-depressive patient, a four-hour trial is performed. It involves two blood samplings and two urine collections, in which lithium and creatine are assayed. Comparison of observed creatinine with a value predicted according to age, morphological characteristics, sex and serum creatinine of the patients allows the interpretation of conflicting results. The estimation of lithium and creatinine clearances of each patient is performed using a computerized or manual method which unfolds a decision procedure. The daily dosage (1.5 to 6 250 mg tablets in two or three daily intakes) is deduced from the according lithium renal clearance (0.4 to over 2 l/h) by means of a nomogram established in previous studies on about 50 patients. The clearance method has been investigated in routine hospital care on a 40 patients sample. The range of satisfactory lithium serum levels during patients monitoring was 0.6-0.9 mmol/l. Accurate dosage regimen forecasting is obtained in 92% of the patients. The percentage observed in a subset of 13 patients with the C24 method, which relies on a unique blood sample 24 hours after the first dose, was much lower (54%). The renal clearance method appears as a robust and reliable technique for individual lithium dosage regimen adjustment in routine care.