Is there an optimal sampling time and number of samples for assessing exposure to fast elimination endocrine disruptors with urinary biomarkers?

In studies investigating the effects of endocrine disruptors (ED) such as phthalates, bisphenols and some pesticides on human health, exposure is usually characterized with urinary metabolites. The variability of biomarkers concentration, due to rapid elimination from the body combined with frequent exposure is however pointed out as a major limitation to exposure assessment. This study was conducted to assess variability of urinary metabolites of ED, and to investigate how sampling time and number of samples analyzed impacts exposure assessment. Urine samples were collected over 6 months from 16 volunteers according to a random sampling design, and analyzed for 16 phthalate metabolites, 9 pesticide metabolites and 4 bisphenols. The amount of biomarkers excreted in urine at different times of the day were compared. In parallel, 2 algorithms were developed to investigate the effect of the number of urine samples analyzed per subject on exposure assessment reliability. In the 805 urine samples collected from the participants, all the biomarkers tested were detected, and 18 were present in >90% of the samples. Biomarkers variability was highlighted by the low intraclass correlation coefficients (ICC) ranging from 0.09 to 0.51. Comparing the amount of biomarkers excreted in urine at different time did not allow to identify a preferred moment for urine collection between first day urine, morning, afternoon and evening. Algorithms demonstrated that between 10 (for monobenzyl (MBzP) phthalate) and 31 (for bisphenol S) samples were necessary to correctly classify 87.5% of the subjects into quartiles according to their level of exposure. The results illustrate the high variability of urinary biomarkers of ED over time and the impossibility to reliably classify subjects based on a single urine sample (or a limited number). Results showed that classifying individuals based on urinary biomarkers requires several samples per subject, and this number is highly different for different biomarkers.

New insights into urine-based assessment of polycyclic aromatic hydrocarbon-exposure from a rat model: Identification of relevant metabolites and influence of elimination kinetics.

A gas chromatography tandem mass-spectrometry method dedicated to the analysis of 50 metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) was applied to urine specimens collected from female Long Evans rats under controlled exposure to a mixture of PAHs (at 7 doses ranging from 0.01 to 0.8 mg/kg, by gavage, 3 times per week for 90 days). On four occasions (day 1, 28, 60 and 90), urine samples were collected over a 24 h period. Among these 50 OH-PAHs, 41 were detected in urine samples. Seven additional OH-PAHs were identified for the first time: 1 corresponding to metabolite of pyrene and 3 of anthracene. Strong linear dose versus urinary concentration relationships were observed for 25 of the 41 OH-PAHs detected in rat urine, confirming their suitability for assessing exposure to their respective parent compound. In addition, some isomers (e.g. 1-OH-pyrene, 3-OH-/4-OH-chrysene, 10-OH-benz[a]anthracene, 8-OH-benzo[k]fluoranthene, 11-OH-benzo[b]fluoranthene and 3-OH-benzo[a]pyrene) that were detected starting from the lowest levels of exposure or even in controls were considered particularly relevant biomarkers compared to metabolites only detected at higher levels of exposure. Finally, on the basis of the excretion profiles (on days 1, 28, 60 and 90) and urinary elimination kinetics of each OH-PAH detected at days 1 and 60, this study highlighted the fact that sampling time may influence the measurement of metabolites in urine. Taken together, these results provide interesting information on the suitability of the analysis of OH-PAHs in urine for the assessment of PAH exposure, which could be taken into consideration for the design of epidemiological studies in the future.

[Gallbladder duplication: diagnosis using cholecystography and ultrasonography]. / La duplication vésiculaire: diagnostic par cholécystographie et échographie.

Duplication of the gallbladder is a rare congenital anomaly. Preoperative diagnosis is sometimes difficult. We report the imaging findings of two cases of gallbladder duplication. Cholecystography and sonography are complementary for this diagnosis.

Sciatic venous drainage demonstrated by varicography in patients with a patent deep venous system.

Varicography, consisting of direct puncture and injection into a varicosity, is the diagnostic procedure of choice in the assessment of varicose veins of the lower limbs. It must be performed in cases of recurrent posterior varicose veins of the leg, after negative ascending phlebography, when looking for possible drainage by a sciatic venous pathway. A series of 7 patients with such sciatic venous drainage is presented. Although infrequent, sciatic venous pathways may explain recurrent varicose veins and alter therapy.

Comparative study of two iodinated contrast media containing 20% iodine in lower-limb phlebography: ioxaglate versus a conventional product.

Forty-eight patients were examined by bilateral ascending phlebography in a crossover, prospective, randomised, double-blind study. A low-osmolar agent (Hexabrix) (ioxaglate, 200 mg iodine/ml) and a dilute conventional contrast medium (Angiografin) (meglumine diatrizoate) with the same iodine concentration were used for each limb alternately. The adverse reactions and the quality of diagnostic data were recorded: the Student paired-t-test showed statistically that ioxaglate containing 200 mg iodine per ml was better tolerated and that diagnostic information was equally good for the deep and ilio-caval systems, but seemed better with diatrizoate for superficial veins with extensive varicosity. The authors conclude that ioxaglate 200 is advantageous overall in lower-limb phlebography from the standpoints of tolerance, diagnostic data and cost.

Usefulness and limitations of sinus echography in the child.

The authors report their preliminary experience in B-mode maxillary sinus echography. The experience takes into account a series of 52 sinuses of children under 10. The study revealed that maxillary sinus echography is a rapid, harmless and quite specific method (i.e. a method which reports few false positives when the existence of possible artifactual echoes is not disregarded), sensitive for secretions, less sensitive for polyps and mucosal thickenings, mainly posterior ones. The method is hampered by the presence of the anterior bone wall, which creates artifacts and thus false positives; yet, it is probably in the child where this handicap is the smallest since normally, in the child, the bone wall is the thinnest. Echography appears to be a really complementary method for radiology, but--according to this preliminary experience, at least--it cannot still pretend to act as a substitute for it. The reproducibility of the method and its reliability, among others in relation to sinusoscopy, are still to be investigated with more accuracy.

['Sciatic" artery and vein. Apropos of 3 cases]. / Artère et veine "sciatiques". A propos de 3 observations.

Three cases of sciatic axis are reported: one case, documented by arteriography, of bilateral persistant sciatic artery, which is a rare but well known embryologic abnormality and two cases, documented by varicography, of sciatic vein. Vascular embryology of lower limb is briefly related; the usefulness of arteriography for pulsatile buttock masses and of varicography concerning some leg's varicose veins are developped.

[Value of varicography in the preoperative assessment of lower limb varicosities (author's transl)]. / Intérêt de la varicographie dans le bilan préopératoire des varices des membres infériurs.

The author's experience of a 100 pilot cases revives the role of varicography for the preoperative evaluation of varicose veins in the lower limbs. This procedure consists of directly injecting the contrast medium into the varicose network. The technique is described in full details, also with several recommendations aimed at preventing potential side effects. The main advantages of direct varicography over "downstream" ascending phlebography include: 1 degrees clearer opacification of the connections between the varicose plexuses, the deep venous line and the paraaxial surface routes; 2 degrees more reliable detection of any deep- seated incompetence. Varicography seems to be particularly useful for the reevaluation of varicose veins after surgical failure; for studying perineal varicosities; and for finding out the source of external varicose veins at the thigh or lower leg.