Does radiotherapy have consequences on plasma concentration of toxic pollutants?
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Biomedical subjects
Publications and source records attributed to G Plomteux.
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BACKGROUND: Body weight loss occurring after a hypoenergetic diet or a gastroplasty could be followed by an increase in blood concentration of potentially toxic pollutants that can interfere with the hormonal system (endocrine disrupters). DESIGN: Thirty obese individuals recruited for gastroplasty were compared before and after treatment with 45 normal-weight people. MEASUREMENTS: Blood samples were analyzed for DDT, DDE, HCB and PCBs no. 28, 52, 101, 118, 138, 153 and 180, by gas chromatography-mass spectrometry. RESULTS: The results indicate clearly that body weight loss occurring after gastroplasty increases plasma concentration of lipophilic pollutants. CONCLUSION: Gastroplasty increases plasma concentration of organochlorine pesticides and PCBs, which could be a risk factor of endocrine disruption. Future longitudinal research will have to determine if the advantages of body weight loss are reduced by this potentially harmful effect.
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.
Xenoestrogens such organochlorine pesticides are known to induce changes in reproductive development, function or behaviour in wildlife. Because these compounds are able to modify the estrogens metabolism, or to compete with estradiol for binding to the estrogen receptor, it may be possible that these products affect the risk of developing impaired fertility, precocious puberty or some kinds of cancer in man.
In a retrospective auxological study of 145 patients seen in Belgium during a 9-year period for treatment of precocious puberty, 28% appeared to be foreign children (39 girls, one boy) who immigrated 4 to 5 years earlier from 22 developing countries, without any link to a particular ethnic or country background. The patients were either adopted (n = 28) or non-adopted (n = 12), the latter having normal weight and height at immigration and starting early puberty without evidence of earlier deprivation. This led to the hypothesis that the mechanism of precocious puberty might involve previous exposure to oestrogenic endocrine disrupters. A toxicological plasma screening for eight pesticides detected p,p'-DDE, which is derived from the organochlorine pesticide DDT. Median p,p'-DDE concentrations were respectively 1.20 and 1.04 ng/ml in foreign adopted (n = 15) and non-adopted (n = 11) girls with precocious puberty, while 13 out of 15 Belgian native girls with idiopathic or organic precocious puberty showed undetectable concentrations (<0.1 ng/ml). A possible relationship between transient exposure to endocrine disrupters and sexual precocity is suggested, and deserves further studies in immigrant children with non-advanced puberty.
Controversy still exists concerning the proper daily dose of methadone to be used in opiate dependency treatment. Because it is admitted that serum methadone concentration may be significantly correlated with the amount of drug available at the receptor level, it could be interesting to predict the methadone daily doses necessary to reach such a serum concentration. The authors have attempted to correlate the serum methadone level with the daily intake, considering the metabolic activity of the patients. A poor correlation was found between methadone doses and methadone serum concentrations (r2 = 0.0409, p = 0.048). The test used to determine the metabolic activity of patients is the 6-OH cortisol/17-OH corticosteroids ratio in urine. This urinary 6-OH cortisol/17-OH corticosteroids ratio was tested because cortisol is metabolized through the same P450 cytochromes as methadone, namely cytochrome P450 3A4. This determination could be of interest because it could be tested before methadone administration to predict optimal doses. But when the authors tried to correlate the methadone serum concentration with the steroid ratio, they failed to find a significant correlation (r2 = 0.0046, N.S.), even when they took into account the daily doses (r2 = 0.0015, N.S.), most probably because of some limitations of the cortisol ratio.
The objectives of the therapeutic drug monitoring are to assume the efficacy and inocuity of a medical treatment and the patient's observance. The administration of a drug to a patient is not always performed in the same conditions and therefore treatment has to be adapted. When necessary, this one is very often based on empiric or very approximative notions and, more seldom, on results of plasmatic concentrations of the drug. The CAPCIL program allows the possibility to objectivate the medical decision and adapt the posology on the basis of two kinetic parameters: the biological half-life and the distribution volume. Indeed, most of pharmacokinetics modifications (drug interactions, diseases, ...) are affecting the two parameters. With basic informations so as height and weight, posology, treatment objectives and peak/trough plasmatic concentrations of the drug, the program is proposing several posology adaptation schemes. The example of a once-a-day administration of amikacin is discussed.
Reduced vitamins K are acting as cofactors of glutamic carboxylation of procoagulant factors (II, VII, IX and X). The reduction of these vitamins is inhibited by oral anticoagulants. The response to antivitamins K is individual and may change during the treatment of a patient. The determinations of plasmatic vitamin K and acenocoumarol may help to explain the mechanism of a resistance to the anticoagulant therapy. Quantifications of vitamin K1 are realized after liquid-liquid extraction with liquid chromatography and fluorescence detection after post-column reduction. For acenocoumarol, plasma concentration is measured, after liquid-liquid extraction, by liquid chromatograph, with ion trap mass spectrometer detector.
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.
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.
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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.
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 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.
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.
Unlike conventional antidepressants, rolipram (a new approach in the treatment of depression) stimulates both the presynaptic and the postsynaptic component of monoaminergic transmission. Several double blind trials are under way to assess the clinical efficacy and safety of this compound. The present study was a randomized, 4-week interindividual double blind double-dummy comparison with desipramine in inpatients with major (DSM-III) and/or endogenous (ICD-9) depressions. After a minimum washout period of three days the patients received either 0.50 mg rolipram or 25 mg desipramine orally t.i.d. for the first three days, then 0.75 mg rolipram or 50 mg desipramine t.i.d. until day 28. Rating tests were based principally on the AMDP-system and the HAMD scale. The study showed no differences between the two drugs as regards the efficacy, but a definite trend in favour of rolipram as regards the side effects and, in particular, anticholinergic effects.
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.