Background: Insulin resistance, glucose dyshomeostasis and oxidative stress are associated to the cardiovascular consequences of obstructive sleep apnea (OSA). The effects of a long-term continuous positive airway pressure (LT-CPAP) treatment on such mechanisms still remain conflicting.Objective: To investigate the effect of LT-CPAP on glucose tolerance, insulin sensitivity, oxidative stress and cardiovascular biomarkers in non-obese non-diabetic OSA patients.Patients & methods: Twenty-eight apneic, otherwise healthy, men suffering from OSA (mean age = 48.9 +/- 9.4 years; apnea-hypopnea index = 41.1 +/- 16.1 events/h; BMI = 26.6 +/- 2.8 kg/m(2); fasting glucose = 4.98 +/- 0.37 mmol/L) were evaluated before and after LT-CPAP by an oral glucose tolerance test (OGTT), measuring plasma glucose, insulin and proinsulin. Glycated hemoglobin, homeostasis model assessment resistance insulin, blood lipids, oxidative stress, homocysteine and NT-pro-brain natriuretic peptide (NT-proBNP) were also measured.Results: LT-CPAP treatment lasted 13.9 +/- 6.5 months. At baseline, the time spent at SaO(2)<90%, minimal and mean SaO(2) were associated with insulin area under the curve during OGTT (r = 0.448, P = 0.011; r = -0.382; P = 0.047 and r = -0.424; P = 0.028, respectively) and most other glucose/insulin homeostasis biomarkers, as well as with homocysteine (r = 0.531, P = 0.006; r = -0.487; P = 0.011 and r = -0.409; P = 0.034, respectively). LT-CPAP had no effect on all the OGTT-related measurements, but increased plasma total antioxidant status (+7.74%; P = 0.035) in a duration-dependent manner (r = 0.607; P < 0.001), and decreased both homocysteine (-15.2%; P = 0.002) and NT-proBNP levels (-39.3%; P = 0.002).Conclusions: In non-obese non-diabetic OSA patients, nocturnal oxygen desaturation is strongly associated to insulin resistance. LT-CPAP does not improve glucose homeostasis nor insulin sensitivity but has a favorable effect on antioxidant capacity and cardiovascular risk biomarkers. (C) 2016 Elsevier Ltd. All rights reserved.

To examine time trends (study 1) and sociocultural factors associated with childhood overweight (study 2) in La Reunion Island.Study 1: a longitudinal analysis of anthropometric data available from health services in the town of Saint-Pierre. Study 2: a case – control study.Study 1: 1753 children born between 1977 and 1996. Study 2: 101 six-year old overweight children sex-matched with 101 non-overweight children.Study 1: overweight at birth (birth weight > 4 kg) and at age 4 and 6 using French references and references from the International Obesity Task Force. Study 2: parental and perinatal data, child's lifestyle and representation of food, all collected from the mother.Study 1: a dramatic increase in the prevalence rate of overweight at 4 and at 6 is observed, more severe in girls. Study 2: multivariate logistic regressions showed that mother's overweight was the only variable significantly associated with overweight in both the sexes. The other associated factors were related to sociocultural and family features and sedentarity. Logistic probability functions derived from these data are proposed as a tool for detection of at risk families.Our results show the need for a targeted prevention of overweight. We offer a proposal based on education and behaviour modification in La Reunion Island.Examiner l'évolution temporelle (étude 1) et les facteurs socioculturels associés au surpoids de l'enfant (étude 2) à l'île de la Réunion.Étude 1 : analyse longitudinale de données anthropométriques issues des services de santé scolaire de la ville de Saint-Pierre. Étude 2 : étude cas témoins.Étude 1 : 1753 enfants, nés entre 1977 et 1996. Étude 2 : 101 enfants de six ans en surpoids, appariés par sexe à 101 enfants normopondéraux.Étude 1 : le surpoids à la naissance (poids de naissance > 4 kg), à quatre et à six ans, en utilisant les références françaises et celles de l'International Obesity Task Force. Étude 2 : données parentales et périnatales, données collectées auprès des mères, relatives au mode de vie de l'enfant et à leur représentation de l'alimentation.Étude 1 : nous avons observé une spectaculaire augmentation de la prévalence du surpoids à quatre et à six ans, en particulier chez les filles. Étude 2 : des régressions logistiques multivariées ont montré que le surpoids de la mère était la seule variable associée au surpoids pour les deux sexes, de façon significative. Les autres facteurs associés sont liés à des caractéristiques socioculturelles et familiales, et à la sédentarité. Les fonctions de probabilité logistiques dérivées de ces données sont proposées comme un outil pour la détection des familles à risques.Nos résultats montrent le besoin de réaliser une prévention ciblée du surpoids. Nous faisons une proposition basée sur l'éducation et des modifications comportementales à la Réunion.

Obstructive sleep apnea (OSA) and metabolic syndrome (MetS) are associated with increased cardiovascular morbidity and mortality. Increased homocysteine is suggested as an independent risk factor for atherosclerosis and cardiovascular disease but remains disputed in OSA. We assessed polysomnography, carotid intima-media thickness (CIMT) and biology in 35 MetS patients, according to the presence (OSA + mets: n = 26) or the absence of OSA (mets: is = 9). In OSA + MetS patients, homocysteine levels were increased compared to MetS subjects (12.8 +/- 3.8 vs. 9.5 +/- 2.5 mu mol/L; P = 0.026). In the whole population, homocysteine correlated with apnea-hypopnea index (AHI) (r = 0.522: P = 0.001) and CIMT (r = 0.376; P = 0.026). Homocysteine was negatively correlated with plasma thiols (r = -0.406; P = 0.017) and positively with urinary 15-F2t-isoprostanes (r = 0.347; P = 0.044). Multivariate regression analysis revealed that AHI (beta = 0.559; P < 0.001) and urinary 15-F2t-isoprostane (beta = 0.310; P = 0.018) were independently associated with homocysteine level. We conclude that homocysteine level was higher in MetS when associated with OSA and proportional to OSA severity. In this context, vascular remodeling appeared more severe and mediated by oxidative stress. (C) 2011 Elsevier B.V. All rights reserved.

Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may unbalance oxidative stress, increasing atherosclerosis. Among oxidative stress markers, 15-F(2t)-isoprostane is considered one of the most sensitive and specific metabolites of lipid peroxidation. To explore the relationship between urinary 15-F(2t)-isoprostane with sleep apnea severity and carotid modifications in nonobese OSA patients, 31 nonobese sleep apnea patients were studied, along with 10 lean subjects without OSA. Patients were assessed by polysomnography, blood pressure measurement, and ultrasonography to determine the carotid intima-media thickness (IMT). Urinary 15-F(2t)-isoprostanes were measured by liquid chromatography-tandem mass spectrometry. Urinary 15-F(2t)-isoprostane concentrations were increased in severe OSA patients compared to control subjects (20.2+/-7.3 vs 12.3+/-2.8 ng/mmol creatinine; P=0.020). Mean carotid IMT was correlated with 15-F(2t)-isoprostane (r=0.532; P<0.001) and with the apnea-hypopnea index (r=0.345; P=0.029). 15-F(2t)-Isoprostane level was related to the night time spent at SaO(2)<90% (r=0.478; P=0.002), the apnea-hypopnea index (r=0.465; P=0.003), and the mean nocturnal SaO(2) (r=-0.424; P=0.007). These results showed a relationship between lipid peroxidation, carotid intima-media thickness, and intermittent hypoxia in nonobese OSA patients, thus reinforcing the hypothesis that oxidative stress could be involved in the early atherosclerotic process.

Cigarette smoke is known to generate free radicals by various mechanisms. In this study involving 30 nonsmokers and 30 smokers, we show that urinary excretion of 5-(hydroxymethyl) uracil (HMUra) was not different in the two groups (6.54 +/- 2.07 vs. 6.70 +/- 1.68 nmol/mmol creatinine). In contrast, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo) excretion increased by 16% (1.16 +/- 0.35 vs. 1.35 +/- 0.50 nmol/mmol creatinine, p = 0.039). Results concerning 8-oxo-dGuo are in agreement with those of previous studies. We observed significant multiple correlations between HMUra and creatinine (r(p) = 0.44), BMI (r(p) = -0.27) and nicotine derivatives (r(p) = 0.26). Multiple correlation analysis showed relations between 8-oxo-dGuo on the one hand, and: creatinine (r(p) = 0.36), nicotine derivatives (r(p) = 0.29), BMI (r(p) = -0.24) on the other.

L’hématopoïèse extra-médullaire est une tumeur bénigne rare, dont la localisation périrénale est exceptionnelle. Elle est secondaire à une stimulation médullaire, le plus souvent une hémolyse chronique chez l’enfant et l’adulte jeune, et un syndrome myéloprolifératif chez l’adulte d’âge mur.Un homme de 62 ans présentait une volumineuse tumeur périrénale bilatérale isolée. Les caractéristiques radiologiques et scintigraphiques (nanocolloïdes marqués au technétium et au chlorure d’indium) étaient en faveur d’un foyer d’hématopoïèse extra-médullaire. L’histologie était en faveur d’un myélolipome. La cause était une sphérocytose héréditaire atypique.Notre observation est la première à décrire une forme frontière entre hématopoïèse extra-médullaire et myélolipome de localisation périrénale révélant une sphérocytose héréditaire atypique à l’âge adulte.Myelolipomas and extramedullary hematopoietic tumors are uncommon benign tumors. They are variably composed of mature adipose tissue and hematopoietic tissue. Myelolipoma is usually observed in the adrenal gland and extramedullary hematopoietic tumors in the liver and spleen but may occasionally be found within solid tumors.A 62-year-old man without previous haematological history presented with a voluminous solitary bilateral renal tumor. Contrast-enhanced ultrasound CT-scan and scintigraphy with technetium-99m-nanocolloid and indium-111-chloride bone marrow were highly suggestive of extramedullary hematopoietic tumor. CT-guided biopsy suggested a diagnosis of myelolipoma. An atypical hereditary spherocytosis, undiagnosed until now, was demonstrated.We report, for the first time to our knowledge, a border form between extramedullary hematopoiesis tumor and myelolipoma of renal localisation revealing a hereditary spherocytosis in an adult patient.

Exchangeable pools of Se after an intravenous injection of 74Se-enriched isotope as sodium selenite were measured in two groups (n 9) of elderly women (free-living aged 64-82 years and institutionalized aged 68-82 years), and a comparison group (n 9) of young women aged 31-40 years to evaluate the effect of age and institutionalization on Se reserves. Dietary Se intake was not different among the three groups. Plasma Se and glutathione peroxidase (EC 1.11.1.9) levels were significantly lower in the institutionalized elderly women (P < 0.05). In each of the three groups, two pools were determined from our model. The size of the first pool and the sum of the two pools were lower in the group of institutionalized elderly women than in the other two groups. The significant correlation between plasma Se level and total Se pool size (r 0.66, P < 0.01) indicated that this last variable could serve as a new marker of Se status. Finally, these data suggest that the Se status of elderly women is more related to lifestyle, in terms of institutionalization or not, than to age per se.

PURPOSE OF THE STUDY:The production of particulate wear debris is a recognised complication of joint arthroplasty. Focus was made on local tissue reactions. Systemic distribution of wear debris are less know. We report two new cases of distant granulomatous reaction.MATERIAL:The first case concerned a 71-year-old man with lymph node histiocytosis incidentally discovered during the staging of a prostatic carcinoma. The second case concerned a 61-year-old man with a visceral granulomatosis reaction (liver, spleen and lymph node) associated to hepatic ans splenic enlargement.METHODS:We realised an histological analysis of several tissue specimens for these two patients and for one case an inductively coupled plasma-mass spectrometry technique (ICPMS).RESULTS:In all specimens we identified a foreign body granulomatous reaction characterized by the presence of particles coming from hip arthroplasty. The ICPMS identified titanium in spleen.DISCUSSION:Distant granulomatous reaction are generally localised in regional lymph nodes and discovered by accident. A systemic granulomatous reaction attributable to wear particles raises the question of long term biocompatibility of prosthetic materials.CONCLUSION:Besides local reaction, it is of utmost importance that physicians involved in prosthetic field take into consideration the possible systemic adverse effect of wear particles from arthroplasty.

The thymine oxidative lesion-5-hydroxymethyluracil (HMUra)-was measured in urine collected from cancer patients. These patients all received chemotherapy using Adriamycin. Adriamycin (ADR) intercalates DNA coils and interferes with normal cell metabolism through diverse biochemical mechanisms that may explain its different actions. The anticancer action of ADR could derive from its interaction with topoisomerase II, resulting in DNA nicking followed by DNA fragmentation and apoptosis. Side effects of ADR-mainly its cardiotoxicity-may derive from the fact that ADR generates superoxide and hydroxyl radicals in two ways: redox-cycling and a Haber-Weiss type reaction due to Fe-ADR complexes. The oxygen free radicals, particularly .OH, are thought to be produced by ADR directly in genomic material and attack all its components. 5-Hydroxymethyluracil is a thymine lesion provoked by these attacks, and it has been proposed as a marker of DNA alterations. In this article, we report the results of a study involving 14 cancer patients treated with ADR. We found that urine HMUra is significantly increased by the anticancer therapy (HMUra (nmol/24 h): 74.4 9.46 vs. 96.3 8.74; p < .01), this increase reveals a higher risk of mutagenesis. Our study is the first to show an in vivo alteration of DNA by ADR. Results also show that thiobarbituric acid reactants increase significantly, and that the vitamin levels for retinol and alpha-tocopherol, which are antioxidant vitamins, are lower at the end of chemotherapy. We suggest to supplement these patients with vitamins A and E, and selenium to reduce the side effects of ADR.

Purpose of the studyThe production of particulate wear debris is a recognised complication of joint arthroplasty. Focus was made on local tissue reactions. Systemic distribution of wear debris are less known. We report two new cases of distant granulomatous reaction.MaterialThe first case concerned a 71-year-old man with lymph node histiocytosis incidentally discovered during the staging of a prostatic carcinoma. The second case concerned a 61-year-old man with a visceral granulomatosis reaction (liver, spleen and lymph node) associated to hepatic ans splenic enlargement.MethodsWe realised an histological analysis of several tissue specimens for these two patients and for one case an inductively coupled plasma-mass spectrometry technique (ICPMS).ResultsIn all specimens we identified a foreign body granulomatous reaction characterized by the presence of particles coming from hip arthroplasty. The ICPMS identified titanium in spleen.DiscussionDistant granulomatous reaction are generally localised in regional lymph nodes and discovered by accident. A systemic granulomatous reaction attributable to wear particles raises the question of long term biocompatibility of prosthetic materials.ConclusionBesides local reaction, it is of utmost importance that physicians involved in prosthetic field take into consideration the possible systemic adverse effect of wear particles from arthroplasty.

OBJECTIVE:The purpose of the study was to assess the actual dietary intakes of zinc (Zn), copper (Cu) and selenium (Se) intakes in relation with some indicators of trace element status in a selected group of hospitalized elderly patients.SUBJECTS:24 elderly women aged 76-99 years were recruited in the Geriatric Department of the Grenoble University Hospital.MEASURES OF OUTCOME:Zn, Cu, and Se dietary intakes were estimated by duplicate portion analysis. Plasma trace element concentrations, Cu-Zn superoxide dismutase (Cu-Zn SOD) and Se glutathione peroxidase (Se GSH-Px) activities were determined in parallel.RESULTS:Mean daily intakes of Zn (5.6 mg), Cu (0.67 mg), and Se (23 micrograms) were low, in relation with poor energy intake and nutrient densities. Zn and Se levels in plasma were lower and plasma Cu increased compared to reference values obtained from healthy younger subjects. Thirty-eight percent of the elderly patients had plasma Zn concentrations < 10.7 mumol/l, but Cu status appeared adequate as suggested by the lack of decline in Cu-Zn SOD activity. A high proportion of plasma Se concentrations < 0.76 mumol/l and the parallel decrease in erythrocyte and plasma GSH-Px activities suggest a Se deficiency in this population.CONCLUSION:Our findings indicate that French hospitalized elderly patients may be at risk of Zn and Se marginal status and present altered antioxidant defenses in relation with low dietary intakes. It underlines the interest of supplementation studies in this population.

In France there is little information on trace element intakes. The present work reports the average daily trace element intakes from French collectivity diets (Grenoble Hospital). Fourteen healthy adult men were enrolled in this trial. Foods and beverages consumed were collected daily for 5 consecutive days, using the duplicate diet technique. Zn, Cu, Mn, and Fe were determined in lyophilised daily samples by flameless atomic absorption spectrometry, whereas Se was determined by gas chromatography-mass spectrometry. The average daily intakes were found to be 1.2 ± 0.05 mg for Cu, 10.8 ± 0.39 mg for Fe, 3.7 ± 0.15 mg for Mn, 10.5 ± 0.47 mg for Zn and 48 ± 3 μg for Se. The micronutrient densities were 0.12 ± 0.005 mg/MJ (0.52 ± 0.021 mg/1000kcal) for Cu, 1.12 ± 0.045 mg/MJ (4.7 ± 0.19 mg/1000kcal) for Fe, 0.39 ± 0.017 mg/MJ (1.64 ± 0.069 mg/1000kcal) for Mn, 1.10 ± 0.049 mg/MJ (4.6 ± 0.20 mg/1000 kcal) for Zn and 5.11 ± 0.362 μg/MJ (21.4 ± 1.51 μg/1000kcal) for Se. Expressed per kg body weight, daily intakes were found to be 16 ± 0.7 μg/kg/d for Cu, 0.14 ± 0.005 mg/kg/d for Fe, 49 ± 2.0 μg/kg/d for Mn, 0.64 ± 0.04 μg/kg/d for Se and 0.14 ± 0.006 mg/kg/d for Zn. These results were in agreement with previous studies in other countries, using the same method. Iron and manganese intakes appeared to be adequate, whereas the requirements recommended by the Food and Nutrition Board, National Academy of Sciences of the United States were not met for Cu, Zn and Se. The question of copper, zinc and selenium deficiencies because of a suboptimal intake and an increased requirement due to illness is raised.

We studied Ca and Mg and trace elements (Zn, Cu, Fe, Mn, Se) in 15 P.K.U. children treated with strict Phe-reduced diet and in a control group. P.K.U. children are significantly lower (p < 0.01) plasma and erythrocyte Se as well as significantly lower (p < 0.01) activities of Glutathione-Peroxidase (GSH-Px), a seleno-dependent enzyme in erythrocytes and in plasma. Concomitantly with defective GSH-Px activities we observe significantly (p < 0.01) increased levels of lipid peroxidation products: malonaldialdehyde (MDA) and organic hydroperoxides (O.H.P.). So, Se supplementation appears to be necessary in low phenylalanine products used in P.K.U. treatment.

Twenty-seven cystic fibrosis patients received selenium supplementation (2.8 micrograms of sodium selenite per kilogram of body weight per day) or a placebo. This 5-month trial was conducted as a double-blind, placebo-controlled study. After an interval of 2 months, treatments of the two groups were interchanged (crossed over) for another 5-month period. A group of healthy subjects, living in the same area, was investigated simultaneously. No selenium deficiency was found either in plasma or in erythrocytes before the supplementation. This result was inconsistent with a previous study performed in 1988 in our laboratory. This change in selenium status can be explained by progress in the nutritional nursing care of children and by the addition of selenium to the diet. During the study, selenium concentrations in plasma decreased when patients received placebo treatment and increased during selenium intake. In one of the two groups a similar variation was found for glutathione peroxidase activities in plasma and erythrocytes, whereas erythrocyte selenium was normal and did not change in any group. Nowadays, in the Grenoble area, the selenium status of cystic fibrosis patients is close to normal. Nevertheless, this study indicates a fragile equilibrium, given that selenium concentrations cn be lowered by placebo or mildly increased by supplementation.