Persistent organic pollutants and transthyretin-bound thyroxin in plasma of Inuit women of childbearing age.

The Inuit population of Nunavik (Northern Quebec, Canada) is highly exposed to persistent organic pollutants (POPs) through their traditional diet. Some POPs, i.e., hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs), pentachlorophenol (PCP), and perfluorooctane sulfonate (PFOS), compete with thyroxin (T4) for binding sites on transthyretin (TTR), a T4 transport protein found in plasma and cerebrospinal fluid. We tested the hypothesis that these TTR-binding compounds decrease circulating concentrations of T4 bound to TTR (T4-TTR) in Inuit women of reproductive age. We measured the concentration of T4-TTR in plasma samples obtained from 120 Inuit women (18-39 years old) by combining native-polyacrylamide gel electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques. Total T4, TTR, and thyroxin-binding globulin (TBG) concentrations were also determined, while POPs levels had been previously measured. The mean T4-TTR concentration was 8.4 nmol/L (SD = 2.4) with values ranging from 2.9 to 14.4 nmol/L. Linear regression analysis revealed that TTR, TBG, and total T4 concentrations were significant predictors (p < 0.002) of T4-TTR levels (total adjusted R-squared = 0.26, p < 0.0001) but not levels of OH-PCBs, chlorophenols, or PFOS. Our results suggest that circulating levels of these TTR-binding compounds in Inuit women of childbearing age are not high enough to affect TTR-mediated thyroid hormone transport. The possibility of increased delivery of these compounds to the developing brain requires further investigation.

[Evaluation of the antihypertensive efficacy of lisinopril and captopril associated with hydrochlorothiazide by ambulatory measurement of arterial pressure]. / Evaluation de l'efficacité antihypertensive du lisinopril et du captopril associés à l'hydrochlorothiazide par mesure ambulatoire de la pression artérielle.

The objective of this study was to evaluate the efficacy, particularly in terms of the 24-hour cover, and the safety of lisinopril 20 mg + hydrochlorothiazide 12.5 mg 5L/HCTZ) and captopril 50 mg + hydrochlorothiazide 25 mg (C/HCTZ) in patients with essential HT requiring two-agent therapy. Twenty patients with a diastolic blood pressure (DBP) between 95 and 120 mmHg after 2 weeks of placebo were randomised to receive, under double-blind conditions, either L/HCTZ or C/HCTZ as a single daily dose for 4 weeks. Clinical examination, laboratory tests and 24-hour ambulatory blood pressure monitoring (ABPM) were performed at the end of the placebo and active treatment periods. L/HCTZ and C/HCTZ significantly lowered SBP and DBP on occasional recordings and on ABPM. The mean fall in blood pressure on ABPM (SBP, DBP, mean of 24-hour recording, diurnal and nocturnal) at 4 weeks was greater with L/HCTZ than with C/HCTZ. Both treatments were effective for 24 hours and did not alter the circadian cycle. The clinical and laboratory safety was good. The blood pressure figures obtained by ABPM were lower than on occasional recordings, emphasising the value of this technique in the evaluation of a patient's poor response to antihypertensive treatment.

Sonography in AIDS-related cholangitis: prevalence and cause of an echogenic nodule in the distal end of the common bile duct.

OBJECTIVE: The purpose of this study was to determine the prevalence and cause of an echogenic nodule in the distal end of the common bile duct seen on sonograms in patients who have AIDS-related cholangitis. SUBJECTS AND METHODS: Sonograms of the liver and bile ducts were obtained in 15 patients who had AIDS-related cholangitis. Both 3.75- and 5-MHz transducers were used in all patients. The appearance of an echogenic nodule in the distal end of the common bile duct was compared with the results of endoscopic retrograde cholangiograms in 12 patients and with biopsies of the papilla of Vater in the first five cases. RESULTS: Sonograms showed a hyperechoic nodule in the distal end of the common bile duct in 10 of the 15 cases. Visualization was improved after oral administration of water. The finding correlated with edema of the papilla of Vater noted on retrograde cholangiograms in eight cases. Biopsy of the papilla of Vater in five cases showed an inflammatory infiltrate. The nodule became smaller in one patient when cholestasis improved after treatment for cryptosporidiosis. CONCLUSION: An echogenic nodule was detected in the distal end of the common bile duct on sonograms in two thirds of patients who had AIDS-related cholangitis. Our findings suggest the abnormality is caused by edema of the papilla of Vater.

[Influence of the position of the arm on the level of clinical arterial pressure]. / Influence de la position du bras sur le niveau de pression artérielle clinique.

The position of the arm in relation to the heart is one of the factors responsible for variations in arterial blood pressure. The purpose of this study was to confirm these variations and their diagnostic and therapeutic consequences. The blood pressure of 59 subjects was measured in supine position with or without support, this support being a device, recently developed by Swedish physicians, that brings the radial notch of the ulna at heart level. The results obtained confirmed the existence of variations in blood pressure values according to the position of the arm in relation to the heart. When measured with the support, blood pressure fell by 5 mmHg for systolic pressure and 4.6 mmHg for diastolic pressure. These results prove the need for standardization of blood pressure measurement in supine position. It is permissible to believe that at this moment a non-negligible proportion of patients (12 percent in our series) is either wrongly regarded as hypertensive or overtreated. In addition, the blood pressure variations induced by the brachial support should be taken into account in the analysis of future epidemiological studies. We conclude that using the brachial support can be recommended for a better evaluation of supine blood pressure measurements.

[Ambulatory blood pressure, reproducibility, variability and change, placebo effect]. / Charge tensionnelle ambulatoire, reproductibilité, variabilité et variation, effet placebo.

Blood pressure assessment by ambulatory recordings is a recent clinical method. What is the reproducibility and variability of the results and what is the circadian variation of blood pressure? How useful is the technique for evaluating therapeutic efficacy? Several groups have reported that the reproducibility is good within a group of patients but that this is not observed in case by case and measurement by measurement analysis; however, when the periods of observation are sufficiently long (several hours) the recordings are comparable. In clinical practice for an individual patient, it would seem better to compare the average daily pressure load, at rest and during activity, which is more reproducible than the hourly average of blood pressure. The circadian variation of blood pressure and short-term (within the hour) or long-term (24 hours) variability have been analysed in depth and although the ambulatory blood pressure shows the same circadian variation as invasive arterial measurement, it does not show instantaneous variability. The placebo effect is not marked when a large group of patients is studied. On the other hand, case by case analysis shows the persistance of this phenomenon in small numbers of cases and, in practice, these results make the maintenance of a placebo period in therapeutic trials a necessity. In conclusion, ambulatory blood pressure recording in daily medical practice enables the study of therapeutic variations in blood pressure over a 24 hour period. However, it does not yet enable satisfactory analysis of the variability of blood pressure.

[Antihypertensive treatments: drug efficacy effect and initial ambulatory blood pressure]. / Traitements antihypertenseurs: effet médicament et niveau de pression artérielle ambulatoire initial.

OBJECTIVE: we used initial whole day blood pressure (BP) level to evaluate antihypertensive therapy in different class of agents. DESIGN AND METHODS: The study was performed with 205 hypertensive patients. All patients had essential mild to moderate hypertension after single-blind placebo run in period. At the end of this period, and after 1 month of active treatment (3 class of agents: angiotensin converting enzyme inhibitors (ACEI) = 117, calcium channel blockers (CCB) = 52, beta-blockers (BB) = 36) casual blood pressure was performed and ambulatory BP was monitored during the whole day. At the start of the study, 91 of 205 patients had an ambulatory diastolic BP less than to 90 mmHg (group I: "normotensive patients") and 114 greater than or = 90 mmHg (group II: "hypertensive patients"). Clinical measurements and whole day BP monitoring are used to assess response to treatment for all patients and for the group I and II. RESULTS: Therapy decreased clinical BP by 19 +/- 15/11 +/- 9 mmHg and average whole day BP by 10 +/- 11/7 +/- 8 mmHg. In the 3 class of agents, there is no difference between group I and II at the start of study. ACEI treatment: In group I, decrease of average whole-day BP by 12/7 and by 11/8 mmHg in group II. In contrast for CCB treatment: 2/2 and 13/7 (p less than 0.001), for BB treatment 10/4 and 13/11. In the 3 class of agents, there is no difference in the clinical BP decreases between group I and II. CONCLUSION: Our data emphasize a significant discrepancy between clinical and ambulatory BP evaluation among patients displaying low ambulatory BP particularly with CCB treatment in contrast with ACEI treatment. In the low group, CCB decreased ambulatory BP less than ACEI did. These results suggest that there is a lesser chance of overtreating "normotensive" patients with CCB than there is with ACEI.

[Comparative study of enalapril, hydrochlorothiazide and their combination in the treatment of essential hypertension]. / Etude comparative de l'énalapril, de l'hydrochlorothiazide et de leur association dans le traitement de l'HTA essentielle.

This was a randomized double-blind, multiclinic, parallel, three treatments group study to compare the safety and efficacy of a fixed-ratio combination of enalapril/hydrochlorothiazide (E/HCTZ: 20/12.5-40/25 N = 46) to enalapril (E = 20-40 mg, N = 49) and hydrochlorothiazide (HCTZ: 12.5-25 mg, N = 51) once daily, in the treatment of patients with moderate to severe essential hypertension (100 less than or equal to supine diastolic blood pressure less than or equal to 120 mmHg). A significant decrease of systolic and diastolic blood pressure was shown in the 3 subgroups of patients. The decrease of blood pressure was significantly greater in the E/HCTZ subgroup. After 8 weeks of treatment, the E/HCTZ group had the greatest proportion of normotensive patients (65.9 p. cent, DBP less than or equal to 90 mmHg) and of responders (81.8 p. cent, diastolic blood pressure decrease greater than 10 mmHg). The treatment groups did not differ significantly with respect to clinical adverse events. The study results document the well-known hyperuricemic effect of diuretics and also indicate that the combination of enalapril and HCTZ ameliorates this effects. In this study plasma potassium was slightly but not significantly decreased by HCTZ. The combination of enalapril and hydrochlorothiazide did not alter this parameter. The results support the conclusion that in the treatment of moderate to severe hypertension, the combination enalapril/HCTZ 20/12.5 to 40/25 mg, taken once daily, is more effective than either its components used alone. This combination is well tolerated, probably due to an adequate enalapril/HCTZ dosage ratio.

Intractable ascites in systemic mastocytosis treated by portal diversion.

A 50-year-old male presented with intractable ascites due to systemic mastocytosis. The diagnosis of systemic mastocytosis was established by histology of the bone marrow which showed mast cell infiltration and fibrosis. Ascites was related to portal hypertension which was documented by esophageal varices at endoscopy and by an increase of wedged-free hepatic venous pressure gradient. Liver biopsy disclosed dense fibrosis of hepatic arterial and portal venule walls, resulting in complete obstruction of some portal radicles. Peliosis hepatis and fibrous deposits in the walls of hepatic venules were also present. Because of intractable ascites and significant malnutrition, a portacaval shunt was performed which cleared ascites and dramatically improved the general condition of the patient.

[Different effects of taurocholate and ursodeoxycholate on the maximal rate of biliary sulfobromophthalein secretion in hamsters]. / Effets différents du taurocholate et de l'ursodésoxycholate sur la vitesse maximale de sécrétion de la bromesulfonephtaléine dans la bile chez le hamster.

Because of the special physiochemical properties of ursodeoxycholate and its tauroconjugate, the effect of these two bile acids on the maximal biliary secretory rate of sulfobromophtalein was compared to that of taurocholate in the hamster. It was confirmed that taurocholate increased the maximal biliary secretory rate of the dye, while it was shown that ursodeoxycholate did not. When the bile acids were infused before sulfobromophtalein, the maximal biliary secretory rate of the dye was significantly higher under taurocholate infusion than under tauroursodeoxycholate and ursodeoxycholate infusions. Under the same conditions, the biliary bile acid output was only slightly decreased by the dye under taurocholate infusion, while it was reduced by approximately one-half under urso- and tauroursodeoxycholate infusions. These observations indicate that ursodeoxycholate is unable to increase the maximal biliary secretory rate of sulfobromophthalein (in contrast to taurocholate). It is suggested that urso- and tauroursodeoxycholate interact with sulfobromophthalein during hepatic transport and that these two bile acids may be transported by the liver by mechanisms different from those of taurocholate.

[Ascites inaugurating systemic mastocytosis (author's transl)]. / Ascite révélatrice d'une mastocytose cutanéo-viscérale.

The authors report a case of urticaria pigmentosa with systemic mastocytosis and review the literature on this occasion. The onset of the disease was marked by the development of ascites. Ascites is rarely mentioned in this affection and remains, as with other manifestations of systemic mastocytosis, without any explanation. The diagnosis was established first on the diffuse mastocyte-infiltration especially in the bone-marrow and second, on the hypersecretion of hormonal factors especially histamine by mastocytes. The symptomatic treatment of this affection is based on histamine inhibitors and disodium cromoglycate seems to be an efficient drug. With the possible development of acute leukemia, the eventual association with a carcinoma and the frequency of serious digestive bleeding, the prognosis may be very poor.

[Upper gastrointestinal haemorrhage in the patients aged over 65 years. The contribution of endoscopy (author's transl)]. / Hémorragies digestives d'origine haute chez les sujets de plus de 65 ans. Apport de l'endoscopie.

One hundred and eighty four patients aged over 65 years and hospitalised for gastrointestinal haemorrhage of high origin underwent emergency oesophago-gastro-duodenoscopy. It was thereby possible to make an aetiological diagnosis in 94.5% of cases. The study demonstrated certain special features: the preponderance of acute gastro-duodenal lesions, possibly explained by the high consumption of gastrotoxic drugs in the elderly subject; the relative frequency of oesophagitis (11%), one out of two cases being responsible for the bleeding; the discovery of a hiatal hernia in 59 patients (1/3 of cases), 25% of them bleeding from a lesion directly related to the latter. Bleeding was in large quantity in 57% of cases. Mortality, which was quite high (17%) appeared to be more related to the underlying general condition than to the haemorrhage itself. Endoscopy gave rise to complications in 8 patients, including 3 who died.

Influence of taurocholate, taurochenodeoxycholate, and taurodehydrocholate on sulfobromophthalein transport into bile.

To test the hypothesis that incorporation of sulfobromophthalein (BSP) into mixed micelles could account for the increase in its biliary transport maximum (Tmax) by bile salts, we have compared in hamsters the influence on BSP Tmax of taurocholate and taurochenodeoxycholate (two micelle-forming physiological bile salts) to that of taurodehydrocholate, a bile salt which, in vitro, does not form micelles. In a first series of experiments, it was observed that taurocholate and taurochenodeoxycholate increased the secretion of phospholipid (40 and 53%, respectively), and cholesterol (50 and 110%, respectively), whereas taurodehydrocholate decreased the secretion of phospholipid (-31%) and cholesterol (-43%). This result suggests that, in vivo, taurodehydrocholate or its metabolites do not form mixed micelles. In a second series of experiments, it was seen that the three bile salts induced a similar increase in BSP Tmax (63% with taurocholate, 52% with taurochenodeoxycholate, and 51% with taurodehydrocholate). These results provide circumstantial evidence for the hypothesis that mixed micelle formation is not an important determinant of maximal BSP secretion into bile.