Human papillomavirus does not play a role in the Barrett esophagus: a French cohort.

The role of human papillomavirus (HPV) in Barrett's esophagus (BE) has been examined but remains unclear. The purpose of the study is to dispute the connection between HPV and BE in a prospective case-control study. Biopsies were performed above and inside the Barrett's segment for BE patients and in the distal third of the esophagus for control patients for histological interpretation and for virological analysis. Biopsies for virological analysis were placed in a virus transport medium and immediately frozen in liquid nitrogen. Virological analysis involved real-time PCR using the SyBr® green protocol with modified SPF10 general primers. A total of 180 patients (119 control and 61 BE, respectively) were included. In BE patients, 31, 18, and 12 patients had, respectively, no dysplasia, low-grade dysplasia, and high grade dysplasia. Overall, nine were found to be HPV positive: five were control patients and four BE patients. HPV positive status was not associated with BE. No factors were associated with HPV, in particular the degree of BE dysplasia. HPV infection appears unlikely to be significant in the etiology of BE compared with control patients. (ClinicalTrials.gov, Number NCT02549053).

Accuracy of water-enema multidetector computed tomography (WE-MDCT) in colon cancer staging: a prospective study.

PURPOSE: To assess the accuracy of water-enema multidetector computed tomography (WE-MDCT) in extra-rectal colon cancer staging. MATERIALS AND METHODS: Fifty-three patients (mean age 70 years) with extra-rectal colon cancer proven by colonoscopy and biopsy were prospectively evaluated by preoperative WE-MDCT. CT scans were both intraluminal (water enema or WE) and intravenous (iodinated) contrast enhanced (CE). All patients underwent surgery. Tumors were classified with the TNM staging system. Noted CT features were: tumor size and location; tumor form and edges; spread to the pericolic fat or neighboring organs; thickening of retroperitoneal fascia; number, size, and enhancement of the peritumoral lymph nodes. Tumors were classified on CT into 3 T-stage groups: T1/T2, T3, and T4. Lymph nodes were classified by their density after injection [positive over 100 Hounsfield units (HU)]. RESULTS: Tumor localization to the specific colon segment was correct in all the cases. The agreement between WE-MDCT staging and histopathology staging was good (k = 0.64). An irregular and bowl-shaped aspect of the external edges of tumor provided excellent sensitivity for T3/T4 inclusion (Se 97.7%, NPV 85.7%). Thickening of a fascia or the abdominal wall provided good specificity for T4 stage (Sp 88.1%, NPV 94.9%). Enhancement over 100 HU of at least one peritumoral lymph node was the best criterion of N+ staging (Sp 67.7%, NPV 87.5%). CONCLUSION: WE-MDCT permits good staging of colon cancer based on objective features.

Fibrosis progression under maintenance interferon in hepatitis C is better detected by blood test than liver morphometry.

We evaluated whether quantitative measurements of liver fibrosis with recently developed diagnostics outperform histological staging in detecting natural or interferon-induced changes. We compared Metavir staging, morphometry (area and fractal dimension) and six blood tests in 157 patients with chronic hepatitis C from two trials testing maintenance interferon for 96 weeks. Paired liver biopsies and blood tests were available for 101 patients, and there was a significant improvement in Metavir activity and a significant increase in blood tests reflecting fibrosis quantity in patients treated with interferon when compared with controls - all per cent changes in histological fibrosis measures were significantly increased in F1 vs F2-4 stages only in the interferon group. For the whole population studied between weeks 0 and 96, there was significant progression only in the area of fibrosis (AOF) (P = 0.026), FibroMeter (P = 0.020) and CirrhoMeter (P = 0.003). With regards to dynamic reproducibility, agreement was good (r(ic) ≥ 0.72) only for Metavir fibrosis score, FibroMeter and CirrhoMeter. The per cent change in AOF was significantly higher than that of fractal dimension (P = 0.003) or Metavir fibrosis score (P = 0.015). CirrhoMeter was the only blood test with a change significantly higher than that of AOF (P = 0.039). AOF and two blood tests, reflecting fibrosis quantity, have high sensitivity and/or reproducibility permitting the detection of a small progression in liver fibrosis over two years. A blood test reflecting fibrosis quantity is more sensitive and reproducible than morphometry. The study also shows that maintenance interferon does not improve fibrosis, whatever its stage.

Distribution of abdominal adipose tissue as a predictor of hepatic steatosis assessed by MRI.

AIM: To evaluate the relationship between the distribution of visceral and subcutaneous adipose tissue and hepatic steatosis assessed using magnetic resonance imaging (MRI). MATERIALS AND METHODS: One T1-weighted, in-/out-of-phase, single-section sequence at the L3/L4 level and one multi-echo gradient MRI (MGRE) sequence were performed on 65 patients [19 females and 46 males; age 57+/-9.5 years; body mass index (BMI) 31+/-5.1kg/m(2)]. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) surfaces, and hepatic steatosis were automatically calculated using in-house software. Weight, height, BMI, waist circumference, hip circumference, and waist:hip ratio were recorded. The probability of having a steatosis greater than 10% on MRI was evaluated by receiver operating characteristic (ROC) curves. RESULTS: The anthropometric parameter best correlated to hepatic steatosis was the waist-to-hip ratio (r=0.301). VAT and proportion of VAT were correlated to liver fat content (r=0.307 and r=0.249, respectively). No significant correlations were found for BMI, hip circumference, and SAT. The area under the receiver operating characteristics (AUROCs) for the relationship between liver steatosis and BMI, waist circumference, waist:hip ratio, VAT surface, and proportion of VAT, were respectively 0.52, 0.63, 0.71, 0.73 and 0.75. CONCLUSION: Adipose tissue distribution is more relevant than total fat mass when assessing the possibility of liver steatosis in overweight patients.

Weight fluctuations and risk for metabolic syndrome in an adult cohort.

OBJECTIVE: Weight gain is a risk factor for metabolic syndrome (MS). However, it is not known whether weight fluctuations (WF) have a deleterious effect upon MS risk. In the present study, we investigated this association in subjects participating in the SU.VI.MAX cohort. METHODS: MS status was assessed at baseline (1994/1995) and at the end of follow-up (2001/2002) using the National Cholesterol Education Program-Adult Treatment Panel III criteria. WF were estimated with four weight measures during follow-up. Odds ratio (OR, 95% confidence interval (CI)) for incident MS cases was evaluated according to four WF groups (no WF and tertiles of WF) in 3553 middle-aged subjects. RESULTS: The OR (95% CI) for MS was 2.06 (1.20-3.52) for the third WF tertile compared to the first tertile. This association was independent of confounding variables, especially relative weight change during follow-up. Subjects without WF had a 2.72-fold increase (1.64-4.53) for MS risk compared to the first tertile of WF. For MS components taken separately, similar associations were found for raised blood pressure, low high-density lipoprotein-cholesterol and increased waist circumference. CONCLUSION: Our results showed that WF was an independent risk factor for MS after 7 years of follow-up. Moreover, subjects without WF were also at risk for MS, due to the highest weight gain during follow-up. These results support the benefits of weight stability and emphasize the importance of weight gain prevention starting from early adulthood.

Promoter adiponectin polymorphisms and waist/hip ratio variation in a prospective French adults study.

BACKGROUND: Adiponectin expression and plasma concentrations are decreased in human and animal models of obesity. Several single nucleotide polymorphisms (SNPs) in the adiponectin gene are known to influence the plasmatic concentration of the encoded protein. Some of these adiponectin polymorphisms have been associated with BMI in cross-sectional studies. OBJECTIVE: The aim of our study was to examine the longitudinal relationships between adiponectin gene polymorphisms and anthropometric indices. DESIGN: Two adiponectin gene (ADIPOQ) SNPs, -11391G>A and -11377C>G, were genotyped in 837 French Caucasian subjects from the SUpplémentation en VItamines et Minéraux Anti-oXydants (SU.VI.MAX) cohort. Anthropometric scores were measured at three clinical examinations over a 7-year period. RESULTS: For -11391G>A as well as for -11377C>G, we detected no association between the variant allele and anthropometric measurements at baseline. Considering longitudinal effects, we detected moderately higher waist-to-hip ratio (WHR) changes for the carriers of the -11391A (P=0.02) and -11377C (P=0.03) allele over the follow-up of the study. -11391G>A and -11377C>G define haplotypes associated also with WHR measurements and their changes over the follow-up of the study. Diploid configurations that combine -11391A and -11377C were associated with significantly higher WHR changes (DeltaCE: P=0.02) compared to other haplotypes. In addition, higher adiponectin levels were observed in AC/AC diplotypes compared to GG/GG carriers (P<0.0001). CONCLUSION: In the SU.VI.MAX study, genetic variations in the adiponectin gene affect abdominal fat gain over life span.

Cathepsin S genotypes are associated with Apo-A1 and HDL-cholesterol in lean and obese French populations.

Cathepsin S (CTSS) is a cysteine protease that has a central role in remodeling the extracellular matrix and, as such, has been implicated in the etiology of cardiovascular disease. This study used five tag single nucleotide polymorphisms (tSNPs) to screen the CTSS gene in healthy lean (n = 1891) and obese French populations (n = 477) for their association with various phenotypes: body mass index, waist-to-hip ratio, glycemia, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo-A1) and apolipoprotein B. Significant associations were identified between rs11576175 tSNP (A/G) and Apo-A1 and HDL-C plasma levels in a sex-specific manner. Lean female subjects homozygous for the minor A-allele had higher levels of circulating Apo-A1 (p = 0.0003), while lean male A/A carriers had higher levels of HDL-C (p = 0.007) compared with the other genotypes. In the obese cohort, associations were found between three tSNPs and Apo-A1 levels in adult female subjects: rs10888390 (G/A), p = 0.01; rs10888394 (T/C), p = 0.03; and rs1136774 (C/T), p = 0.02; however, only rs10888390 remained significant in a combined model (p = 0.03). These results provide the first evidence that CTSS sequence variations are associated with two human metabolic risk factors for cardiovascular diseases: plasma Apo-A1 and HDL-C concentrations.

High plasma aldosterone and low renin predict blood pressure increase and hypertension in middle-aged Caucasian populations.

Plasma aldosterone and renin levels have been associated with blood pressure increase and 3-4 year incidence of hypertension in a middle-aged North American community in Framingham. To confirm these findings in a different population, a nested case-control study was performed in a national sample of 1984 French non-hypertensive volunteers aged 45-64 year and followed for 5 years. Cases and controls (individuals becoming hypertensive or remaining non-hypertensive on follow-up) were individually matched on sex, diastolic and systolic pressures at baseline. Multivariable regression models show that plasma aldosterone and renin are respectively positively and negatively associated with the increase in systolic pressure (P=0.01 and 0.001) and the risk of hypertension (22% increase and 16% decrease per s.d. increment in the log, P=0.04 and 0.07). These associations are mostly observed in the lowest tertiles of dietary sodium and potassium intakes where plasma aldosterone is positively associated with the increase in systolic pressure (P=0.01 and 0.08) and the risk of hypertension (59 and 69% increase per s.d. increment in the log, P=0.02 and 0.01), whereas plasma renin is negatively associated with the increase in systolic pressure (P=0.0004 and 0.004) and the risk of hypertension (31 and 28% decrease per s.d. increment in the log, P=0.03 and 0.05). These results reinforce the hypothesis that high plasma aldosterone and low plasma renin levels precede blood pressure increase and the occurrence of hypertension in middle-aged Caucasian populations.

Plasma n-6 and n-3 polyunsaturated fatty acids as biomarkers of their dietary intakes: a cross-sectional study within a cohort of middle-aged French men and women.

OBJECTIVE: To measure the correlations between habitual intakes of individual n-6 and n-3 polyunsaturated fatty acids (PUFA) and their percentages in total plasma fatty acids in a population of adult men and women. SUBJECTS/METHODS: Two hundred and seventy-six men and 257 women aged 45-60 (men) or 35-60 (women) at baseline, volunteers of the French SU.VI.MAX cohort. Fifteen 24-h record questionnaires were used to estimate the habitual intake of energy, total fat and linoleic, alpha-linolenic acid, arachidonic, eicosapentaenoic (EPA), n-3 docosapentaenoic (DPA) and docosahexaenoic (DHA) acids. Fatty acid composition of fasting plasma total lipids has been determined at baseline. RESULTS: Dietary intakes of linoleic acid, arachidonic acid, EPA and DHA were weakly but significantly correlated (0.16

Screening for therapeutic trials and treatment indication in clinical practice: MACK-3, a new blood test for the diagnosis of fibrotic NASH.

BACKGROUND: The composite histological endpoint comprising nonalcoholic steatohepatitis (NASH) and NAFLD activity score ≥4 and advanced fibrosis (F ≥ 2) ("fibrotic NASH") is becoming an important diagnostic target in NAFLD: it is currently used to select patients for inclusion in phase III therapeutic trials and will ultimately be used to indicate treatment in clinical practice once the new drugs are approved. AIM: To develop a new blood test specifically dedicated for this new diagnostic target of interest. METHODS: Eight Hundred and forty-six biopsy-proven NAFLD patients from three centres (Angers, Nice, Antwerp) were randomised into derivation and validation sets. RESULTS: The blood fibrosis tests BARD, NFS and FIB4 had poor accuracy for fibrotic NASH with respective AUROC: 0.566 ± 0.023, 0.654 ± 0.023, 0.732 ± 0.021. In the derivation set, fibrotic NASH was independently predicted by AST, HOMA and CK18; all three were combined in the new blood test MACK-3 (hoMa, Ast, CK18) for which 90% sensitivity and 95% specificity cut-offs were calculated. In the validation set, MACK-3 had a significantly higher AUROC (0.847 ± 0.030, P ≤ 0.002) than blood fibrosis tests. Using liver biopsy in the grey zone between the two cut-offs (36.0% of the patients), MACK-3 provided excellent accuracy for the diagnosis of fibrotic NASH with 93.3% well-classified patients, sensitivity: 90.0%, specificity: 94.2%, positive predictive value: 81.8% and negative predictive value: 97.0%. CONCLUSION: The new blood test MACK-3 accurately diagnoses fibrotic NASH. This new test will facilitate patient screening and inclusion in NAFLD therapeutic trials and will enable the identification of patients who will benefit from the treatments once approved.

Dietary iron intake and serum ferritin in relation to 7.5 years structure and function of large arteries in the SUVIMAX cohort.

AIM: Few studies have investigated the relationship between iron stores and measures of atherosclerosis. Most of these studies were cross-sectional and yielded conflicting results. We aimed to assess the relationship between serum ferritin concentrations and dietary iron intake measured at baseline and 7.5 year pulse wave velocity (PWV), intima-media thickness (IMT) and plaques in a group of 824 men and women without known CVD, cancer or hemochromatosis. METHODS: The SUVIMAX study is a randomized double-blind, placebo-controlled primary prevention trial designed to test the effect of antioxidant supplementation in reducing ischemic cardiovascular diseases and cancer. RESULTS: In multivariate analyses, no association was found between baseline serum ferritin levels and IMT 7 years later (beta (95% CI)=0.003 (-0.005;0.011) in men; -0.005 (-0.013;0.004) and -0.001 (-0.011;0.009) in women, before and after menopause, respectively), plaques (OR (95% CI)=1.09 (0.88;1.34) in men; 0.93 (0.66;1.31) and 0.95 (0.70;1.29) in women, before and after menopause, respectively) or PWV (beta (95% CI)=0.078 (-0.154;0.310) in men; -0.018 (-0266;0.231) in women before and after menopause). Results for dietary iron intake were similar. CONCLUSION: Our results do not support the hypothesis that dietary iron intake and body iron stores are deleterious to the structure and function of large arteries in subjects free of CVD, cancer or hemochromatosis.

Consumption of black, green and herbal tea and iron status in French adults.

OBJECTIVE: A number of potential health effects have lately been accorded to tea consumption. It is, however, not clear whether an increase in tea consumption increases the risk of iron depletion in a normal apparently healthy adult population. We have therefore evaluated this. DESIGN: Cross-sectional study. SUBJECTS: A total of 954 men (aged 52-68 years) and 1639 women (aged 42-68 years), who were participants of SU.VI.MAX Study, completed a detailed questionnaire on tea consumption. To determine the iron status of the participants, a venous blood sample was drawn and serum-ferritin was measured. Iron depletion was defined as a serum ferritin concentration <16 microg/l. Three 1-day food records were used to estimate the intake of other dietary enhancing or inhibiting factors of iron absorption, which were included in the logistic regression models. RESULTS: The mean serum-ferritin concentration was not related to black, green and herbal tea consumption in men, pre- or postmenopausal women. Also the risk of iron depletion was in the multivariate model not related to any kind of tea drinking or to the strength of tea, the infusion time or the time of tea drinking. CONCLUSIONS: The data suggest that normal apparently healthy adults are not at risk of iron depletion owing to any kind of tea drinking.

Factors influencing blood concentration of retinol, alpha-tocopherol, vitamin C, and beta-carotene in the French participants of the SU.VI.MAX trial.

OBJECTIVES: The data was collected during the inclusion step of the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) study. This article deals with the study's first stage before any supplementation. The collected data shows factors influencing blood vitamin concentrations and may reflect the vitamin status of volunteers. MATERIAL AND METHODS: A total of 12,741 volunteers were enrolled in the SU.VI.MAX study 7,713 women 35-60 years of age and 5,028 men 50-60 years of age. The serum concentrations of retinol, alpha-tocopherol, and beta-carotene were measured by HPLC, and vitamin C concentration was measured by spectrofluorimetry using a Technicon continuous flow analysis apparatus. The volunteers recorded their 24 h diet by means of a specific terminal that was connected to the main central computer of the SU.VI.MAX study. Volunteers recorded the food they consumed daily and estimated its quantity by comparing pictures of dishes. RESULTS: Retinol concentration was significantly higher in older volunteers, and was higher in male than in female volunteers. Smoking had no effect on serum retinol, but the latter was higher in the autumn than in the winter. Serum retinol concentrations were higher in the Southwest region and lower in the Ile-de-France and East-Centre regions. Serum alpha-tocopherol was slightly higher in older volunteers and also higher in male volunteers. Serum alpha-tocopherol was significantly lower in smokers, and former smokers showed intermediate levels. Like retinol, serum alpha-tocopherol was higher in the autumn, and higher in the Southwest as compared to the East-Centre Serum beta-carotene was slightly higher in younger volunteers, and concentrations were higher in female than in male volunteers. Tobacco smoking decreased serum beta-carotene, which was higher in the autumn, and higher in the East, West, and North regions. Serum vitamin C was higher in female volunteers, and was not age related. Serum vitamin C was lower in smokers, was season-dependant, but contrary to fat-soluble vitamins, concentrations were higher in the winter and spring. Serum vitamin C was higher in the Southeast and East-Centre, but lower in the North region. CONCLUSION: These results suggest that serum retinol concentrations depend on gender, age, seasons, and location of residence. Similarly, serum alpha-tocopherol concentrations were slightly influenced by age, but more by tobacco smoking, seasons, dietary intake, and location of residence. Serum concentrations of beta-carotene depend on gender, age, smoking status, dietary intake, and location of residence. Serum vitamin C concentrations depend on gender, age, smoking status, seasons, dietary intake, and location of residence. Contrary to beta-carotene, retinol concentrations were higher in male than in female volunteers. Such a reversed relation suggests a higher beta-carotene-retinol conversion in male volunteers.

[Fruits and vegetables intake in the SU.VI.MAX study and systolic blood pressure change]. / Consommation de fruits et de légumes et évolution de la pression artérielle dans la cohorte SU.VI.MAX.

BACKGROUND: In intervention studies (DASH), high fruits and vegetables intake lower blood pressure (BP). Less is known on long-term effects of fruits and vegetables intake on BP, especially in European population. OBJECTIVE: To study the relation between fruits and vegetables intake and BP change in the SU.VI.MAX study. METHOD: In the SU.VI.MAX study (1994-2002), BP was measured and information on medical treatment was collected during two clinical examination session in 1995-1996 and 2001-2002. Dietary information came from 24 h dietary records completed every two months, by each volunteer during the first two years of follow-up. We performed a transversal analysis of BP measured at the first clinical examination in 6 427 subjects aged 36-62 years. A longitudinal analysis including subjects without hypertension at baseline was performed on BP change between the two examination (n=2958). RESULTS: At first examination, after adjusting for main confounding factors, subjects reporting high vegetables intake (last quintile) had a lower (-1.6 mmHg, p trend <0.01) systolic BP (SBP) than subjects reporting lower intake (first quintile). High fruits intake was slightly associated with lower SBP (1.1 mmHg, NS). At the end of the follow-up, the mean increase of SBP was of 9.5 mmHg. This increase was 2.2 mmHg lower (p < 0.003) in the last quintile of vegetables intake. No similar relation was observed with fruits intake. CONCLUSION: These results suggest that vegetables intake may be associated with lower BP and a lower increase of BP over years. This last association may have implications for the prevention of hypertension which appears with aging.

[Antioxidant supplements and risk of hypertension in the SU.VI.MAX trial: relationship to plasma antioxidants]. / Supplementation en antioxydants et risque d'hypertension artérielle dans l'étude SU.VI.MAX: relations avec les antioxydants plasmatiques.

The object of this work was to determine the risk of hypertension after 6.5 years'- follow-up of supplementation in vitamins and antioxidant minerals at nutritional doses in the SU.VI.MAX trial. The authors also studied the association with plasma concentrations of antioxidants at inclusion and at long term. This was a randomised nutritional primary prevention study including 5086 adults of the SU.VI.MAX trial. After 6.5 years' follow-up, no effect of supplementation on the risk of developing hypertension could be shown compared with the placebo group: odds ratios (OR IC 95%): 1.04 (0.87-1.23) in men and 1.10 (0.95-1.29) in women. Besides, in the male 2nd and 3rd tertiles of serum beta-carotene levels at inclusion the risk of hypertension was lower [multivariate OR: 0.70 (0.44-1.12) and 0.53 (0.33-0.86) for placebo, and 0.59 (0.37-0.94) and 0.67 (0.42-1.07) for the supplemented groups]. The authors conclude that, despite a reverse relationship in men between the plasma concentrations of beta-carotene and the risk of hypertension, supplementation in antioxidants at nutritional doses had no effect on the risk of developing hypertension after 6.5 years' follow-up.

[Phototype, vitamin D status and bone mineral density among women at risk of osteoporosis]. / Phototype, statut en vitamine D et densité minérale osseuse chez des femmes à risque d'ostéoporose.

PURPOSE: The aim of this study was to test the influence of phototype and vitamin D status feature on the bone mineral density (BMD) of the femoral neck in a group of middle-aged women considered at risk of osteoporosis (low levels of vitamin D [25(OH)D3<78 nmol/L] and hyperparathyroidism [parathormone level>36 pg/mL]). METHODS: This two-step study was conducted on 122 French women enrolled in the SUVIMAX (supplémentation en vitamines et minéraux antioxydants: antioxidant vitamin and mineral supplementation) cohort. The impact of various variables on BMD, including age, body mass index (BMI), vitamin D status, alcohol intake, sun exposure intensity and phototype was investigated using regression models. RESULTS: No statistical link was found between BMD and the variables documenting vitamin D status and parathormone levels, nor phototype. Nevertheless, fair phototypes tended to be associated with lower BMD values. However, BMD decreased with age and increased with BMI and physical activity level. CONCLUSIONS: Whatever their phototype, adult women concerned about precarious vitamin D status should undergo a vitamin D supplementation in combination with an adequate calcium intake all year long and a proper sun protection. Moreover, a physical activity maintenance should provide an additional benefit for prevention of osteoporosis.

Serum concentrations of beta-carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population.

OBJECTIVE: To assess relationships between energy, nutrient and food intakes, alcohol consumption, smoking status and body mass index (BMI), and serum concentrations of beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc. METHODS: Data on health status, alcohol consumption, smoking habits, anthropometric data and biochemical measurements were obtained in 1821 women aged 35-60 y and 1307 men aged 45-60 y, participant to the SU.VI.MAX Study. Data on dietary intake were available on a subsample who reported six 24-h dietary records during the first 18 months of the study. RESULTS: Women had higher baseline serum beta-carotene and vitamin C concentrations and lower concentration for serum vitamin E, zinc and selenium than men. In women, younger age was associated with lowered mean concentration of serum beta-carotene, vitamin E and selenium. In men, only differences were observed for serum zinc, which was lower in older men. Current smokers of both sexes had significantly lower concentrations of serum beta-carotene, vitamin C and selenium, and, only in women, of vitamin E, than nonsmokers. Alcohol consumers had lower concentrations of serum beta-carotene and higher selenium concentrations. Serum beta-carotene and vitamin C concentrations were lower in obese subjects. There were positive associations of dietary beta-carotene, vitamin C and E with their serum concentrations. Age, nutrient and alcohol intakes, serum cholesterol, BMI and smoking status explained 15.2% of the variance of serum beta-carotene in men and 13.9% in women, and 10.8 and 10.0% for serum vitamin C, and 26.3 and 28.6% for serum vitamin E, respectively. CONCLUSION: Serum antioxidant nutrient concentrations are primarily influenced by sex, age, obesity, tobacco smoking, alcohol consumption and especially dietary intake of those antioxidant nutrients.

Is there a glycemic threshold for mortality risk?

OBJECTIVE: To determine whether there are thresholds for fasting and for 2-h glucose above which the risk of death from all causes and from coronary heart disease (CHD) increases. RESEARCH DESIGN AND METHODS: We studied 23-year mortality data from the Paris Prospective Study of the 7,018 men, aged 44-55 years, who were not known as diabetic at the baseline examination. The effect of glucose concentrations on mortality was studied using the observed relative risks and an age-adjusted Cox proportional hazards model. RESULTS: For all causes of death, there were J-shaped relationships with both fasting and 2-h glucose concentrations, and the lowest observed death rates were in the intervals centered on 5.5 mmol/l for fasting glucose and 5.0 mmol/l for 2-h glucose. The death rates for CHD were low in this population: for fasting glucose, the hazards ratio was best modeled by a positive linear relationship; for 2-h glucose, it was modeled by a J-shaped curve and the lowest observed death rate was in the interval centered on 6.0 mmol/l. CONCLUSIONS: In the Paris Prospective Study, there were no clear thresholds for fasting or 2-h glucose concentrations above which mortality sharply increased; in the upper levels of the glucose distributions, the risk of death progressively increased with increasing fasting and 2-h glucose concentrations.

Identification of a duplicated V3 domain in NS5A associated with cirrhosis and hepatocellular carcinoma in HCV-1b patients.

BACKGROUND: The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. OBJECTIVES: In a French multicenter study, we investigated the clinical and epidemiological features of a new HCV genotype 1b strain bearing a wide insertion into the V3 domain. STUDY DESIGN: We studied NS5A gene sequences in 821 French patients infected with genotype 1b HCV. RESULTS: We identified an uncharacterized V3 insertion without ORF disruption in 3.05% of the HCV sequences. The insertion comprised 31 amino-acids for the majority of patients; 3 patients had 27 amino-acids insertions and 1 had a 12 amino-acids insertion. Sequence identity between the 31 amino-acids insertions and the V3 domain ranged from 48 to 96% with E-values above 4e(-5), thus illustrating sequence homology and a partial gene duplication event that to our knowledge has never been reported in HCV. Moreover we showed the presence of the duplication at the time of infection and its persistence at least during 12 years in the entire quasispecies. No association was found with extrahepatic diseases. Conversely, patients with cirrhosis were two times more likely to have HCV with this genetic characteristic (p=0.04). Moreover, its prevalence increased with liver disease severity (from 3.0% in patients without cirrhosis to 9.4% in patients with both cirrhosis and HCC, p for trend=0.045). CONCLUSIONS: We identified a duplicated V3 domain in the HCV-1b NS5A protein for the first time. The duplication may be associated with unfavorable evolution of liver disease including a possible involvement in liver carcinogenesis.

Puberty-associated differences in total cholesterol and triglyceride levels according to sex in French children aged 10-13 years.

PURPOSE: To assess the relationships between lipid levels and sexual maturity, independently of age-related differences, and to investigate possible differences related to sexual maturity across the percentiles of the lipid distributions. METHODS: Fasting serum total cholesterol and triglyceride concentrations were measured in 6577 boys and 6605 girls, aged from 10 to 13 years, with different Tanner stages. The total cholesterol and triglyceride mean and percentile levels were estimated according to age and Tanner stage by ordinary least squares and percentile regression models, separately in both sexes. RESULTS: In boys and girls, total cholesterol levels were significantly associated with pubertal stage after controlling for age. At age 12, the estimated mean levels in boys varied from 4.82 mmol/L for Tanner 1 to 4.41 for Tanner 5. The corresponding values were 5.05 and 4.62 mmol/L in girls, for whom the association with maturity was stronger in the upper than in the lower percentiles (p < 0.0001); between the extreme Tanner stages, the 95th percentiles of total cholesterol differed by 0.80 mmol/L, in comparison to 0.19 mmol/L for the 5th percentiles. Therefore, 1. 8% of girls and 0.7% of boys were classified differently whether Tanner stage was used or not to assess hypercholesterolemia (concentrations in the upper 5% of the distributions). Triglycerides were positively related to sexual maturity independently of age, but the discrepancies between classifications were lower; 1.1% in girls and 0.4% in boys. CONCLUSIONS: Our findings emphasize the importance of sexual maturity, even for a given age, for interpreting lipid levels in children.