[Dioxin, poisoning information or brainwashing? On Seveso's and Yushchenko's acne]. / La dioxine, info ou intox? A propos de l'acné de Seveso et de Yushchenko.

The generic term "dioxin" covers more than 400 chemicals of which less than 30 prove to be toxic. Such compounds are involved in environmental pollutions and in food contaminations. Some selected dioxins have also been used as a non-lethal chemical weapon. The assessment of the impact on health needs a precise toxicological identification. Without that basic assessment, a discrepancy may appear between the real risk linked to the exposure and the concerns and fear generated in the population, particularly because in animals the toxic concentrations of dioxins can interfere with some hormonal systems, alter immunity, induce chloracne, and participate in the development of sarcomas, lymphomas and some carcinomas. They may be responsible for some birth defects.

Venlafaxine: the relationship between dose, plasma concentration and clinical response in depressive patients.

The relationship between plasma drug level of venlafaxine and daily intake was studied in 89 major depressive inpatients. In addition, changes over time in severity were assessed weekly in a subgroup of 22 depressed patients using the Montgomery and Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression improvement scale. The results indicate a moderate correlation between daily doses and plasma concentrations, together with a higher relationship between improvement on the MADRS scale and concentration. Moreover, plasma concentrations (for venlafaxine and its predominant metabolite, O-desmethylvenlafaxine) up to 400 microg/l can be considered as effective, as already suggested in a previous study. No case of venlafaxine discontinuation occurred during the longitudinal study, and the incidence of adverse event, as estimated by the Target Emergent Symptoms and Side-effects scale, was low, suggesting that the drug is well tolerated for such plasma concentrations.

Relationship between clinical effects, serum drug concentration, and concurrent drug interactions in depressed patients treated with citalopram, fluoxetine, clomipramine, paroxetine or venlafaxine.

The relationship between clinical effects and plasma concentrations of citalopram, fluoxetine, clomipramine, paroxetine and venlafaxine was studied in 119 cases of major depression. Clinical effects were evaluated using the Clinical Global Impression (CGI) improvement scale. Antidepressants were quantified by a separative chromatographic methodology. Plasma concentrations in responder patients were compared with the plasma concentrations proposed in literature as effective values. We found that the usual therapeutic window is convenient for citalopram and clomipramine, but could be reduced for fluoxetine and increased for venlafaxine and paroxetine. Concurrent drug interactions were also evaluated and clomipramine or citalopram plasma levels were found to be influenced by the presence of associated drugs. A larger study is needed, taking into account not only plasma concentrations and clinical effects, but also some pharmacokinetic data, especially the metabolic activity characterising the patient, and the presence or not of associated drugs. Copyright 2000 John Wiley & Sons, Ltd.

Fatal overdosage with cisplatin.

This paper presents a case of fatal overdosage due to an accidental massive administration (750 mg instead of 170 mg) of cisplatin, an anticancer agent, to a 63-year-old patient suffering from lymphoma. Platinum was measured in various postmortem samples by means of inductively coupled plasma mass spectrometry. Heart and peripheral blood concentrations of platinum were 1515 and 1253 micro g/L, respectively. Concentrations in urine and bile were 1038 and 501 micro g/L, respectively. Renal dialysis was started immediately after the end of cisplatin perfusion, when the mistake was noticed, but the patient deceased at day 16, presenting renal and hepatic insufficiency, ototoxicity, and pancytopenia.

[Environmental chemical pollution and toxic risk for humans: the particular role of organochlorine pesticides]. / Pollution chimique de l'environement et risque toxique pour l'homme. Le rôle particulier des dérivés pesticides organochlorés.

There is an increasing concern about environmental exposure to multiple chemicals and adverse changes in reproductive development, function, or behaviour in wildlife. The major group of environmental chemicals, such as organochlorine pesticides, polychlorinated biphenyls (PCBs) and other xenoestrogens are currently known to have estrogenic effects in vertebrates or fishes. Recent studies suggest that past exposure to such estrogenic compounds may affects the risk of developing breast cancer, precocious puberty, or impaired fertility in man.

[Adaptation on the ABA-100 of the optimized method of measurement of serum aspartate aminotransferase activity]. / Adaptation sur ABA-100 de la méthode optimisée de mesure de l'activité sérique de l'aspartate aminotransférase.

The analytical modifications necessary for adaptation of the SFBC technic for measurement of the activity of TGO method and those obtained by the technic adapted on ABA 100 suggest that the modifications proposed have no influence on the result of the enzyme estimation. The activation of TGO by addition of its coenzyme was assessed using mathematical models uniting the values of TGO recorded with and without pyridoxal phosphate. It has been shown that the parabolic model is more suitable than the linear model to explain the relation between transaminase activity determined without pyridoxal phosphate and that measured in the presence of the coenzyme. Using estimations carried out in 850 blood donors, it was possible to show that the reference interval of TGO lay between 7 and 28 mUI/ml. In man, the value of TGO is statistically higher than in women. On the other hand between 20 and 60 years there does not seem to be any significant difference depending on age.

[Measurement of the hepatic, intestinal and bony fractions of the serum alkaline phosphatase (author's transl)]. / Mesure des fractions hépatique, intestinale et osseuse des phosphatases alcalines du sérum.

A trial of thermostability associated with immunological estimation of alkaline phosphatase of intestinal origin permits evaluation of the various fractions of serum alkaline phosphatase. The usual values, drawn up on the basis of data collected in 35 subjects in apparently good health and chosen among a laboratory population, indicate that on average, 9 per cent of the enzyme activity is of intestinal origin whereas the hepatic and bony fractions are respectively 25 per cent and 67 per cent. On the basis of the results presented in this paper, it appears that the method proposed is able, in the presence of raised alkaline phosphatase, to determine the tissue origin of this blood abnormality. Whereas the coefficient of correlation drawn up between the values of 5-nucleotidase and those of the hepatic fraction of serum alkaline phosphatase determined by the technic described is satisfactory, if the raised alkaline phosphatase is of hepatic origin, it becomes poor or nil, if the latter is from an extra-hepatic source. In the cases of hyperphosphatasemia of extra-hepatic origin, there is excess evaluation of the hepatic alkaline phosphatase, if one concludes from the results of 5-nucleotidase.

[Postprandial variations of several biological blood tests]. / Variations postprandiales de quelques tests biologiques sanguins.

One generally concede that a blood test must be taken on an empty stomach, to abstain from the influence of food on the serum concentration of the different parameters evaluated. To confirm that, the authors have studied, on 22 subjects in good health and from 20 to 25 years old, the postprandial variations of the serum parameters the most required in their laboratory. Some blood tests executed at different moments after the ingestion of a standardized meal prove that some meaningful variations exist. So, it seems evident that the blood tests have to be taken on an empty stomach, and early in the morning.

[Statistical evaluation of biochemical data by the method of discrimination analysis. Selection of the discriminant biochemical variables. Attempted biochemical discrimination of intrahepatic cholestasis, extrahepatic obstruction and liver cancer]. / Traitement statistique des données biochimiques par la méthode d'analyse discriminante. Sélection des variables biochimiques discriminantes. Essai de discrimination biochimique de la cholostase intrahéatique de l'obstacle extrahépatique et du cancer du foie

An original method of statistical treatment of biological data is proposed. It permits satisfactory biochemical classification of 322 patients divided up into 3 groups : intrahepatic cholestasis (235 patients), extrahepatic obstruction (44 patients) and carcinoma of the liver (43 patients). On the basis of 32 tests, it was possible to define discriminating areas permitting satisfactory diagnosis in 95 per cent of published cases. The reduction in the number of tests necessary for diagnosis was considered. The selection technic used was original to the extent that it dose not require, like most methods used today, the determination of better individual discriminators, but the establishment of a better discriminating subunit, obtained from the initial subunit composed of a group of variables. From the 32 parameters contained in the standard liver function tests, a search for a better discriminating subunit consisting of the best four tests, permitted the authors to select a group of 10 tests : bilirubin, alkaline phosphatase, 5-nucleotidase, Thymolturbidity, Cetavlon test, serum albumin, total LDH, TGP (ALAT), OCT, GLDH, of which the discriminating value remains very satisfactory.

[Attempt to adapt measurement of serum iron levels to the Centrifichem with a direct method using bathophenanthroline sulfonate-guanidine. Value and limits]. / Essai d'adaptation du dosage du fer sérique sur Centrifichem par une méthode directe à la bathophénanthroline sulfonée-guanidine. Intérêt et limites.

The authors have studied a direct automated colorimetric determination of iron serum on Centrifichem. Accuracy and linearity are the same than these obtained by the SFBC recommended method. Precision is poor: the coefficient of variation is about 15% for low values. No alteration in the absorbance is recognized by bilirubin, even in the serum which contains 342 mumol.l-1 of bilirubin. The value of serum iron increases significantly as hemoglobin and copper are added to the serum.

[Biochemical characterization of a high-molecular weight alkaline phosphatase in a patient with cholangiocarcinoma (alpha-1 alkaline phosphatase)]. / Caractérisation biochimique d'une phosphatase alcaline de haute masse moléculaire chez un patient atteint de cholangiocarcinome (alpha 1-PAL).

The authors analysed the alkaline phosphatases present in the serum of a patient with cholangiocarcinoma. The electrophoretic analysis on cellulose acetate revealed two bands of AP activity in positions alpha 1 and alpha 2. The more anodic of the isoenzymes of AP presented most of the features of the high molecular weight isoenzyme found in human bile, except that it was non-competitively inhibited by L-homoarginine. This feature, which distinguishes this isoenzyme form the biliary isoenzyme of AP, indicates the existence of another type of high molecular weight isoenzyme present in malignant hepatic diseases.

[Therapeutic monitoring of antidepressant drugs]. / Le controle thérapeutique des médicaments antidépresseurs.

Depression is a pathology frequently observed in general medicine (10%). Treatment of depression makes great use of drugs from different pharmacological classes. The optimal posology is difficult to establish, and clinicians prefer to avoid side effects by prescribing low regimen. This study is related to an evaluation of seric antidepressant concentrations in comparison with the daily doses in a large psychiatric population. Side effects of drugs are appreciated by enzymatic determinations.

[Reference values of erythrocyte ferritin in children and adults]. / Valeurs de référence de la ferritine érythrocytaire chez l'enfant et l'adulte.

The erythrocyte ferritin content was measured in 183 healthy subjects in age from 4 to 68 years; 80 were male and 103 were female. In children between the ages of 4 and 12 years there is no significant difference in the mean value between boys and girls. In females the erythrocyte ferritin concentration is independent of age. After 12 years of age the erythrocyte ferritin content is higher in men. Reference intervals were determined by the two quantiles 0.05 and 0.95. The reference interval is 3-24 age by cell in boys between 4 and 12 and females between 4 and 63; the reference interval is 5-38 age by cell in males between 13 and 68 years of age.

Modification of the selected method for the determination of serum iron. Substitution of bathophenanthroline by ferene S.

The previously selected method (1977) for the measurement of iron in human serum has been modified by the working group on Iron and Iron-Transport Proteins (Sociéte Française de Biologie Clinique). Ferene S is used as the chromogen, it is more sensitive and cheaper than bathophenanthroline. The sample size has been reduced from 2 to 0.5 ml. No interference could be shown with high concentrations of bilirubin, copper or hemoglobin.

[Multicenter study of sialic acid deficient transferrin determined by two chromatographic techniques]. / Etude multicentrique du dosage de la transferrine déficiente en acide sialique par deux techniques chromatographiques.

Serum carbohydrate-deficient-transferrin (CDT) was measured by a micro anion-exchange chromatography/enzyme immunoassay. Results obtained on 245 sera analyzed in four laboratories were compared. Moreover, one laboratory used a commercial kit with ready-to-use microcolumns and a radioimmunoassay for measuring eluted CDT. Imprecision was judged to be satisfactory. Within-assay coefficients of variation ranged from 5 to 10%, between-assay coefficients of variation ranged from 9 to 18%. Between-laboratory results were compared for 110 sera from control subjects (daily alcohol intake < 40 g), for 57 sera from chronic ethylic subjects and for 78 sera from patients suffering from non-alcoholic liver diseases. There was a large between-laboratory variation, suggesting that the method is difficult to standardize and that results are not transferable. Results of enzyme and radioimmunoassays were compared on 325 sera. The best correlation was obtained in the groups of ethylic subjects and those with non-alcoholic hepatic diseases. Finally the performance of the CDT-test was evaluated by calculating sensitivity and specificity. With both methods specificity was very high (> 85%) but sensitivity was poor (< 50%).

[The coefficient of saturation of iron in transferrin]. / A propos du coefficient de saturation en fer de la transferrine.

Theoretical iron fixation capacity of transferrin (FCT) can be calculated on its immunochemical titration: (FCT (mumol/l = transferrin (g/l) x 25). Today, its reckoning is more advisable to serum total iron binding capacity measurement. The authors studied the effects of this new proceeding upon usual values interval of transferrin saturation (i.e. serum iron/FCT ratio). The mean value and the distribution of transferrin saturation appear displaced with regard to those achieved by chemical measurement of serum total iron binding capacity. We discuss interpretation of transferrin saturation related to its methods of determination and its semiological interest.

The effect of intravenous administration of WEB 2086 on PAF-induced platelet aggregation in healthy Friesian calves.

The in vivo ability of the specific PAF-antagonist WEB 2086, a thienotriazolodiazepine, to inhibit platelet-activating factor (PAF) in cattle was investigated by in vitro determination of platelet aggregation curves. WEB 2086 was infused intravenously into a group of 5 healthy male Friesian calves in a dose of 3 mg/kg over 1 min. The resultant inhibition peaked between 30 min and 1 h after administration of WEB 2086. The inhibition was significantly reduced after 3 h and became non-significant after 6 h, but maximal pre-treatment aggregation had not been restored by 24 h after the injection of WEB 2086. These results confirm previous results obtained in vitro and suggest that WEB 2086 is a potent antagonist of PAF activity in calves. They also suggest that further clinical studies with WEB 2086 in cattle are desirable.

[Reference values of serum transferrin in newborn infants, children and adults]. / Valeurs de référence de la transferrine sérique chez le nouveau-né, l'enfant et l'adulte.

The authors have studied the evolution of serum transferrin concentration in relation with age (newborn child, infant, adult). The mean concentration of serum transferrin is the lowest for neonates (2.15 g/l). At 10 months, it increases to reach a value of about 3.10 g/l then reduces at 24 (3.0 g/l) and 48 months (2.8 g/l). By the 4 to 18 years subjects, serum transferrin is approaching that of 10 months children (3.15 g/l). At last it doesn't support any modification during all the adult life. The diversity of the obtained results dependent of the used technique and/or of the laboratory, justifies that each one defines his own reference values.

[Tamoxifen in the treatment of breast cancer]. / Le tamoxifène dans le traitement du cancer du sein.

Tamoxifen is the most often prescribed non steroidal antioestrogenic agent in the world for breast cancer. Worldwide collaboration. has centralized the results, of different trials throughout the world on oral adjuvant therapy in the early stages of breast cancer. A significative regression of the tumour was observed in most cases. Moreover, recent epidemiological studies suggest that tamoxifen could prevent new contralateral primary tumours. The risk of the disease should thus be reduced by the prophylactic use of antioestrogens such as tamoxifen. Investigations using a variety of models have evaluated the effect of tamoxifen on tumour promotion and cell growth. Tamoxifen-induced growth inhibition is associated with major changes in biochemical events in cultured human breast cancer cells including cell proliferation or growth factor production. Growth inhibition of oestrogen-responsive human breast cancer cells is associated with an induced secretion of autoinhibitory polypeptides (TGF beta) and an antagonistic effect on the synthesis of proliferative proteins (TGF alpha,...). The first step in the mechanism of action of the drug is binding of tamoxifen to the oestrogen receptors. Development of resistance to tamoxifen treatment is a great problem in treatment of breast cancer patients and the mechanism of resistance will require further study: under the influence of the drug, tumours could become remodelled as selected subpopulations emerge resistant-tamoxifen. The fact that some breast cancers which are oestrogen receptor-negative respond to antioestrogen suggests that parallel but separate pathways for oestrogen and antioestrogen action may exist. This paper summarizes the results of the most recent studies concerning this promising drug.

[Alcohol, drugs, medication and highway safety in Belgium. Belgian Toxicology and Trauma Study Research Group]. / Alcool, drogues, médicaments et sécurité routière en Belgique. Belgian Toxicology and Trauma Study Research Group.

The BTTS study (Belgian Toxicology and Trauma Study) was performed in Belgium between January 15th 1995 and June 15th 1996. The purpose was to investigate how frequently the drivers involved in road accidents were driving under the influence of psychotropic drugs. Two thousand fifty-three blood tests were performed of which 207 in the Liège region. The results obtained at the national level are compared to those obtained at the level of the Liège region. In both cases, the BTTS study allows the conclusion that a considerable proportion of drivers involved in road accidents resulting in significant traumatic consequences were driving under the influence of substances with psychotropic properties.