Altered Response to A(H1N1)pnd09 Vaccination in Pregnant Women: A Single Blinded Randomized Controlled Trial

Background

Pregnant women were suspected to be at particular risk when H1N1pnd09 influenza became pandemic in 2009. Our primary objective was to compare the immune responses conferred by MF59®-adjuvanted vaccine (Focetria®) in H1N1pnd09-naïve pregnant and non-pregnant women. The secondary aims were to compare influences of dose and adjuvant on the immune response.

Methods

The study was nested in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC₂₀₁₀) pregnancy cohort in 2009-2010 and conducted as a single-blinded block-randomised [1∶1∶1] controlled clinical trial in pregnant women after gestational week 20: (1) 7.5 µg H1N1pnd09 antigen with MF59-adjuvant (Pa7.5 µg); (2) 3.75 µg antigen half MF59-adjuvanted (Pa3.75 µg); (3) 15 µg antigen unadjuvanted (P15 µg); and in non-pregnant women receiving (4) 7.5 µg antigen full adjuvanted (NPa7.5 µg). Blood samples were collected at baseline, 3 weeks, 3 and 10 months after vaccination, adverse events were recorded prospectively.

Results

58 pregnant women were allocated to Pa7.5 µg and 149 non-pregnant women were recruited to NPa7.5 µg. The sero-conversion rate was significantly increased in non-pregnant (NPa7.5 µg) compared with pregnant (Pa7.5 µg) women (OR = 2.48 [1.03–5.95], p = 0.04) and geometric mean titers trended towards being higher, but this difference was not statistically significant (ratio 1.27 [0.85–1.93], p = 0.23). The significant titer increase rate showed no difference between pregnant (Pa7.5 µg) and non-pregnant (NPa7.5 µg) groups (OR = 0.49 [0.13–1.85], p = 0.29).

Conclusion

Our study suggests the immune response to the 7.5 µg MF59-adjuvanted Focetria® H1N1pnd09 vaccine in pregnant women may be diminished compared with non-pregnant women.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01012557","term_id":"NCT01012557"}}NCT01012557.     

Individual Variations in Serum Melatonin Levels through Time: Implications for Epidemiologic Studies

Melatonin, a marker for the circadian rhythm with serum levels peaking between 2AM and 5AM, is hypothesized to possess anti-cancer properties, making it a mechanistic candidate for the probable carcinogenic effect of circadian rhythm disruption. In order to weigh epidemiologic evidence on the association of melatonin with cancer, we must first understand the laboratory and biological sources of variability in melatonin levels measured in samples. Participants for this methodological study were men enrolled in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO). We measured serum melatonin levels over a five year period in 97 individuals to test if melatonin levels are steady over time. The Pearson correlation coefficient between two measures separated by 1 year was 0.87, while the correlation between two measures separated by 5 years was to 0.70. In an additional cross-sectional study of 292 individuals, we used Analysis of Variance to identify differences in melatonin levels between different lifestyle and environmental characteristics. Serum melatonin levels were slightly higher in samples collected from 130 individuals during the winter, (6.36±0.59 pg/ml) than in samples collected from 119 individuals during the summer (4.83±0.62 pg/ml). Serum melatonin levels were lowest in current smokers (3.02±1.25 pg/ml, p = 0.007) compared to never (6.66±0.66 pg/ml) and former (5.59±0.50 pg/ml) smokers whereas BMI did not significantly affect serum melatonin levels in this study. In conclusion, the high 5 year correlation of melatonin levels implies that single measurements may be used to detect population level associations between melatonin and risk of cancer. Furthermore, our results reiterate the need to record season of sample collection, and individual characteristics in order to maximize study power and prevent confounding.     

Leucocyte Ascorbic Acid Levels and Vitamin C Intake in Older People

Leucocyte ascorbic acid (L.A.A.) levels and vitamin C intake were measured in a random sample of men and women aged 62-94 years. L.A.A. distributions are positively skewed but log normal. L.A.A. mean values show no age difference in men but are significantly lower in older women. The mean value for all women (23·88μg/10⁸ cells) is significantly higher than that for all men (18·11 μg/10⁸ cells). L.A.A. values are significantly higher in both sexes in the six months July to December. Vitamin C intake distributions are positively skewed but not improved by log transformation. No significant age or sex differences were found except that a significantly greater proportion of men over than of those under 70 years have intakes less than 30 mg daily. Mean intake is significantly higher in men but not in women in the six months April to September, though in both sexes a significantly greater proportion have intakes less than 30 mg daily in October to March compared with April to September. Fifty per cent. of men and 58% of women have intakes less than 30 mg daily, 23·6% of men and 28·1% of women have intakes less than 20 mg daily, and 4·7% of men and 3% of women have intakes less than 10 mg daily. These percentages increase during the winter. A moderate correlation is present between vitamin C intake and L.A.A. level. L.A.A. levels increase in parallel with but lag behind seasonal increases in vitamin C intake.     

Blood lipid concentrations and other cardiovascular risk factors: distribution,prevalence, and detection in Britain

To establish the distribution of blood lipid concentrations and the prevalences of other risk factors for cardiovascular disease in Britain 12 092 men and women aged 25-59 in Glasgow, Leicester, London, and Oxford were studied. Subjects were selected by opportunistic case finding, in which patients consulting their general practitioner for any reason were offered a health check by appointment, or random selection from age-sex registers, in which an invitation for a health check was posted. The overall rate of response was 73%, being 91-94% by opportunistic case finding and 36-63% by random selection. At the health check subjects answered a brief questionnaire about risk factors for cardiovascular disease, and their height, weight, and blood pressure were recorded; a blood sample was taken for measuring plasma concentrations of cholesterol, triglyceride, high density lipoprotein cholesterol, and glucose.The mean cholesterol concentrations were 5·9 (SD 1·2) and 5·8 (1·2) mmol/l in men and women, respectively. In London the mean value was 5·5 (1·2) mmol/l for both men and women and was significantly lower than mean values in the three other centres, among which there were no significant differences. In men and women aged 25-29 concentrations were similar but they increased in men until the age of 45-49, after which they showed no further increase; in women concentrations did not increase until the age of 40-44 and by the age of 50-59 values were higher than in men. Mean triglyceride concentrations were significantly higher in men than in women (1·8 (1·4) v 1·3 (0·9) mmol/l, respectively), and trends with age were similar to those for cholesterol concentrations, except that at no age were values higher in women than in men. Mean triglyceride values overall were higher in Glasgow and London than in Oxford and Leicester. Body mass index was higher in Glasgow and London than in the other two centres and correlated with systolic and diastolic blood pressures and triglyceride concentration. In addition, subjects in Glasgow smoked significantly more than those in the other centres. These observations could contribute to the higher rate of coronary heart disease in Glasgow. Plasma lipid concentrations and the prevalences of other risk factors for cardiovascular disease were similar in subjects selected by opportunistic case finding and by random selection.In Britain cholesterol values have changed little during the past 12 years despite dietary recommendations and health education. Identifying subjects at particularly high risk of coronary heart disease is required to supplement advice to the general population to reduce the prevalence of this disease. Opportunistic case finding would be an appropriate method of identifying such subjects in general practice, although none of the potential markers for hyperlipidaemia was particularly useful in identifying all subjects at high risk.     

Growth hormone,prolactin, and corticosteroid responses to insulin hypoglycaemia in alcoholics

Plasma growth hormone (GH), prolactin, and corticosteroid responses to insulin-induced hypoglycaemia were studied in 24 men with progressive alcoholism who had been abstinent for two to seven days. Ten normal healthy subjects (five men, five women) served as controls for comparing GH and prolactin responses, while cortisol responses were studied in a further six male controls. Blood samples were taken at intervals after an injection of soluble insulin (0·1 U/kg body weight). All patients developed adequate hypoglycaemia (blood glucose <2·2 mmol/l (<39·6 mg/100 ml)) and nine had impaired GH responses (peak concentration <10 mU/1). Prolactin concentrations fell or remained unchanged in nine patients, eight of whom also had impaired GH responses. In seven patients corticosteroid concentrations decreased from basal concentrations, and six of these patients had impaired GH responses. All three hormone responses were impaired in several patients, and significant correlations were found between the GH and prolactin responses at 45 and 60 minutes. GH response was not correlated with age, duration of drinking, duration of alcoholism, or admitted alcohol intake. GH responses were significantly lower in patients who had the most severe withdrawal symptoms. Our observations of impaired stress responses in some recently abstinent alcoholics may have important implications for the management of alcohol withdrawal syndrome.     

Circadian variations in plasma growth hormone and prolactin in the infant rat: Comparison with the adult pattern

Radioimmunoassayable (RIA) plasma growth hormone (GH) and prolactin (PRL) levels were determined at 3 hr intervals during a controlled 24-hr light-dark cycle in 10-day-old male and female rats; parallel measurements were made of brain monoamines (MA's), dopamine (DA), norepinephrine (NE) and serotonin (5-HT) concentration. Plasma GH and PRL and brain MA levels found in infant rats were compared to the same determinations made during the 24-hr cycle in 50-day-old male rats. GH levels were rather uniform and did not show circadian periodicity in the plasma of infant rats, while PRL levels showed a diurnal surge in the late afternoon hr (1800). In adult rats, GH levels exhibited wide fluctuations during the 24-hr cycle and no circadian periodicity, while PRL levels showed one diurnal (1500–1800) and one nocturnal (2400) surge. A pulsatile GH secretion was found in adult rats sampled at 15 min intervals over a period of 2 hr, which seemed to be lacking in infant rats. In the brain of infant rats, DA and NE levels exhibited circadian patterns which resembled the ones present in the brain of adult rats, whereas no circadian variations were present in 5-HT levels.     

DNA Methylation as a Biomarker for Cardiovascular Disease Risk

Background

Elevated serum homocysteine is associated with an increased risk of cardiovascular disease (CVD). This may reflect a reduced systemic remethylation capacity, which would be expected to cause decreased genomic DNA methylation in peripheral blood leukocytes (PBL).

Methodology/Principal Findings

We examined the association between prevalence of CVD (myocardial infarction, stroke) and its predisposing conditions (hypertension, diabetes) and PBL global genomic DNA methylation as represented by ALU and Satellite 2 (AS) repetitive element DNA methylation in 286 participants of the Singapore Chinese Health Study, a population-based prospective investigation of 63,257 men and women aged 45–74 years recruited during 1993–1998. Men exhibited significantly higher global DNA methylation [geometric mean (95% confidence interval (CI)): 159 (143, 178)] than women [133 (121, 147)] (P = 0·01). Global DNA methylation was significantly elevated in men with a history of CVD or its predisposing conditions at baseline (P = 0·03) but not in women (P = 0·53). Fifty-two subjects (22 men, 30 women) who were negative for these CVD/predisposing conditions at baseline acquired one or more of these conditions by the time of their follow-up I interviews, which took place on average about 5·8 years post-enrollment. Global DNA methylation levels of the 22 incident cases in men were intermediate (AS, 177) relative to the 56 male subjects who remained free of CVD/predisposing conditions at follow-up (lowest AS, 132) and the 51 male subjects with a diagnosis of CVD or predisposing conditions reported at baseline (highest AS 184) (P for trend = 0.0008) No such association was observed in women (P = 0.91). Baseline body mass index was positively associated with AS in both men and women (P = 0·007).

Conclusions/Significance

Our findings indicate that elevated, not decreased, PBL DNA methylation is positively associated with prevalence of CVD/predisposing conditions and obesity in Singapore Chinese.     

Blood concentrations of gonadotrophins, prolactin and gonadal steroids in males and in non-pregnant and pregnant female African elephants (Loxodonta africana)

No seasonal variation in any of the hormones measured was apparent in males or females. Testosterone levels in males increased around puberty (10-11 years) and remained significantly higher in adult than prepubertal males. This was not accompanied by any significant change in levels of LH, FSH or prolactin. In non-pregnant females there was no apparent difference in levels of LH, FSH or prolactin with age. There was a significant increase in progesterone around puberty (12 years) but there was considerable overlap in values between prepubertal and adult females. During pregnancy, progesterone levels were significantly higher than in non-pregnant females with maximum levels occurring at mid-pregnancy (9-12 months). However, there was considerable overlap in values between non-pregnancy and pregnancy. Concentrations of LH and FSH decreased significantly during mid-pregnancy while prolactin levels increased dramatically during pregnancy; after 7 months of gestation until term levels were always at least 8 ng/ml greater than in any non-pregnant female. It is suggested that this consistent increase in plasma/serum levels of prolactin can be used to diagnose pregnancy in the elephant.     

Plasma Testosterone and Testosterone Binding Affinities in Men with Impotence,Oligospermia, Azoospermia,and Hypogonadism

Mean plasma testosterone levels (± S.D.), using Sephadex LH-20 and competitive protein binding, were 629 ± 160 ng/100 ml for a group of 27 normal adult men, 650 ± 205 ng/100 ml for 27 impotent men with normal secondary sex characteristics, 644 ± 178 ng/100 ml for 20 men with oligospermia, and 563 ± 125 ng/100 ml for 16 azoospermic men. None of these values differ significantly. For 21 men with clinical evidence of hypogonadism the mean plasma testosterone (± S.D.), at 177 ± 122 ng/100 ml, differed significantly (P < 0·001) from that of the normal men.The mean testosterone binding affinities (as measured by the reciprocal of the quantity of plasma needed to bind 50% of ³H-testosterone tracer) were similar for normal, impotent, and oligospermic men. Though lower for azoospermic men the difference was not significant (P >0·1). For 12 of the 16 hypogonadal males the testosterone binding affinity was normal, but raised binding affinities, similar to those found in normal adult females or prepubertal boys (about twice normal adult male levels), were found in four cases of delayed puberty. These findings help to explain why androgen therapy is usually useless in the treatment of impotence.     

Movies and TV Influence Tobacco Use in India: Findings from a National Survey

Background

Exposure to mass media may impact the use of tobacco, a major source of illness and death in India. The objective is to test the association of self-reported tobacco smoking and chewing with frequency of use of four types of mass media: newspapers, radio, television, and movies.

Methodology/Principal Findings

We analyzed data from a sex-stratified nationally-representative cross-sectional survey of 123,768 women and 74,068 men in India. All models controlled for wealth, education, caste, occupation, urbanicity, religion, marital status, and age. In fully-adjusted models, monthly cinema attendance is associated with increased smoking among women (relative risk [RR]: 1·55; 95% confidence interval [CI]: 1·04–2·31) and men (RR: 1·17; 95% CI: 1·12–1·23) and increased tobacco chewing among men (RR: 1·15; 95% CI: 1·11–1·20). Daily television and radio use is associated with higher likelihood of tobacco chewing among men and women, while daily newspaper use is related to lower likelihood of tobacco chewing among women.

Conclusion/Significance

In India, exposure to visual mass media may contribute to increased tobacco consumption in men and women, while newspaper use may suppress the use of tobacco chewing in women. Future studies should investigate the role that different types of media content and media play in influencing other health behaviors.     

Serum Uric Acid Concentrations in Meat Eaters,Fish Eaters,Vegetarians and Vegans: A Cross-Sectional Analysis in the EPIC-Oxford Cohort

Introduction

Circulating concentrations of uric acid may be affected by dietary components such as meat, fish and dairy products, but only a few studies have compared uric acid concentrations among individuals who exclude some or all of these foods from their diet. The aim of this study was to investigate differences in serum uric acid concentrations between meat eaters, fish eaters, vegetarians and vegans.

Subjects and Methods

A sample of 670 men and 1,023 women (424 meat eaters, 425 fish eaters, 422 vegetarians and 422 vegans, matched on age and sex) from the European Prospective Investigation into Cancer and Nutrition Oxford cohort were included in this cross-sectional analysis. Diet was assessed using a semi-quantitative food frequency questionnaire and serum concentrations of uric acid were measured. Mean concentrations of uric acid by diet group were calculated after adjusting for age, body mass index, calcium and alcohol intake.

Results

In both men and women, serum uric acid concentrations differed significantly by diet group (p<0.0001 and p = 0.01, respectively). The differences between diet groups were most pronounced in men; vegans had the highest concentration (340, 95% confidence interval 329–351 µmol/l), followed by meat eaters (315, 306–324 µmol/l), fish eaters (309, 300–318 µmol/l) and vegetarians (303, 294–312 µmol/l). In women, serum uric acid concentrations were slightly higher in vegans (241, 234–247 µmol/l) than in meat eaters (237, 231–242 µmol/l) and lower in vegetarians (230, 224–236 µmol/l) and fish eaters (227, 221–233 µmol/l).

Conclusion

Individuals consuming a vegan diet had the highest serum concentrations of uric acid compared to meat eaters, fish eaters and vegetarians, especially in men. Vegetarians and individuals who eat fish but not meat had the lowest concentrations of serum uric acid.     

Salivary and serum cortisol levels during recovery from intense exercise and prolonged,moderate exercise

The aim of this study was to compare serum (SERc) and salivary cortisol (SALc) responses during recovery from two different exhaustive exercises to determine peak cortisol sampling time and the agreement between SERc and SALc levels. Twelve healthy men underwent a maximal treadmill graded exercise to exhaustion (MEx) and a prolonged, submaximal cycle exercise in the heat for 90 min (PEx) while SERc and SALc samples were taken in parallel at baseline, end of exercise, and 15 min intervals over one hour of recovery. MEx and PEx significantly increased SERc and SALc levels (p < 0.01) while absolute SERc levels were approximately 7-10 folds higher than SALc. SERc and SALc showed highly positive correlation (R = 0.667-0.910, p < 0.05) at most sampling times and only a few individual values were out of 95% limit of agreement when analyzed by Bland-Altman plots. However, peak SERc levels (MEx: 784.0±147, PEx: 705.5±212.0 nmol · L⁻¹) occurred at 15 min of recovery, whereas peak SALc levels (MEx: 102.7±46.4, PEx: 95.7±40.9 nmol · L⁻¹) were achieved at the end of exercise in MEx and PEx. The recovery trend of SERc and SALc also differed following MEx and PEx. Activity of 11β-hydroxysteroid dehydrogenase type 2 enzymes may be suppressed following MEx compared to PEx. In conclusion, sampling for peak SERc and SALc levels should take into account their evolution and clearance characteristics as well as type of exercise performed, whereas SALc appeared to be a more sensitive marker than SERc for the measurement of cortisol responses during exercise recovery.     

Gender Differences in the Association between Socioeconomic Status and Subclinical Atherosclerosis

Objectives

This study explored the pattern of associations between socioeconomic status (SES) and atherosclerosis progression (as indicated by carotid intima media thickness, CIMT) across gender.

Design

Cross-sectional analysis of a sample of 5474 older persons (mean age 73 years) recruited between 1999 and 2001 in the 3C study (France). We fitted linear regression models including neighborhood SES, individual SES and cardiovascular risk factors.

Results

CIMT was on average 24 µm higher in men (95% CI: 17 to 31). Neighborhood SES was inversely associated with CIMT in women only (highest versus lowest tertiles: −12.2 µm, 95%CI −22 to −2.4). This association persisted when individual SES and risk factors were accounted for. High individual education was associated with lower CIMT in men (−21.4 µm 95%CI −37.5 to −5.3) whereas high professional status was linked to lower CIMT among women (−15.7 µm 95%CI: −29.2 to −2.2). Adjustment for cardiovascular risk factors resulted in a slightly more pronounced reduction of the individual SES-CIMT association observed in men than in women.

Conclusion

In this sample, neighborhood and individual SES displayed different patterns of associations with subclinical atherosclerosis across gender. This suggests that the causal pathways leading to SES variations in atherosclerosis may differ among men and women.     

Cardio-Respiratory Reference Data in 4631 Healthy Men and Women 20-90 Years: The HUNT 3 Fitness Study

Purpose

To provide a large reference material on key cardio-respiratory variables in a healthy population of Norwegian men and women aged 20–90 years.

Methods

Sub maximal and peak levels of cardio-respiratory variables were measured using cardiopulmonary exercise testing during treadmill running.

Results

The highest peak ventilation among men (141.9±24.5 L·min⁻¹) and women (92.0±16.5 L·min⁻¹) was observed in the youngest age group (20–29 years, sex differences p<0.001) with an average 7% reduction per decade. The highest tidal volumes were observed in the 30–39 and 40–49 year age groups among men (2.94±0.46 L) and women (2.06±0.32 L) (sex differences p<0.001), with a subsequent average 6% reduction per decade. Ventilatory threshold and respiratory compensation point were observed at approximately 77% and 87% of peak oxygen uptake (VO_2peak) among men and women, respectively. The best ventilatory efficiency (EqVCO_2Than) was observed in the youngest age group (20–29 years) in both men (26.2±2.8) and woman (27.5±2.7) (sex differences p<0.001) with an average 3% deterioration in ventilatory efficiency per decade.

Conclusion

This is the largest European reference material of cardio-respiratory variables in healthy men and women aged 20–90 years, establishing normal values for, and associations between key cardio-respiratory parameters. This will be useful in clinical decision making when evaluating cardiopulmonary health in similar populations.     

Postural influence on maternal capillary oxygen and carbon dioxide tension

The effect of posture on maternal capillary blood Po₂ and Pco₂ was studied in pregnant and non-pregnant women. There was a significant decrease of Po₂ (mean 13·0 mm. Hg) and significant decrease of Pco₂ (mean 2·4 mm. Hg) when pregnant women sat up, but these changes did not occur in the non-pregnant. These findings may be relevant to debate on the optimum posture for labour.     

The Metabolic Syndrome and ECG Detected Left Ventricular Hypertrophy – Influences from IGF-1 and IGF-Binding Protein-1

Background and Aims

The metabolic syndrome (MetS) is associated with an increased risk for left ventricular hypertrophy (LVH) and cardiovascular mortality. The aim of this study was to investigate potential influences from insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP-1) on the relationship between the MetS and LVH, also taking into account the role of physical activity (PA), use of oestrogen and gender.

Methods and Results

In a population-based cross-sectional study of 60-year-old men (n = 1822) and women (n = 2049) participants underwent physical examination and laboratory tests, including electrocardiography (ECG), and completed an extensive questionnaire. Women showed higher levels of IGFBP-1 than men (37.0 vs. 28.0 µg/l, p<0.001), and women with LVH had lower levels of IGFBP-1 than women without LVH (31.0 µg/l vs. 37.0 µg/l, p<0.001). Furthermore, women with low levels of IGFBP-1 had a significantly increased risk of having LVH (crude OR≈2.5). When stratifying for PA and oestrogen, respectively, a weaker association between IGFBP-1 and LVH was demonstrated in physically active men and women, compared to inactive individuals, as well as in women using oestrogen, compared to non-users.

Conclusion

In a representative sample of 60-year-old Swedish men and women, the main findings were higher levels of IGFBP-1 in women than in men; lower levels of IGFBP-1 in women with LVH, compared to women without LVH; and an increased risk of having LVH in women with low levels of IGFBP-1. The association between IGFBP-1 and LVH was diminished in physically active men and women, as well as in women using oestrogen.     

Association of Estimated Glomerular Filtration Rate with Hemoglobin Level in Korean Adults: The 2010–2012 Korea National Health and Nutrition Examination Survey

PurposeLittle is known about anemia in patients with early renal dysfunction. We aimed to investigate the association of hemoglobin level and anemia prevalence with estimated glomerular filtration rate (eGFR) decline using a nation-wide representative sample of the adult Korean population.MethodsIn total, 17,373 participants (7,296 men; weighted n = 18,330,187; mean age, 44.2±0.3 years; 9,886 women, weighted n = 18,317,454; mean age, 46.9±0.3 years) were included. eGFR was divided into 5 groups: Group 1, ≥105; Group 2, 90–104; 75–89; Group 4, 60–74; and Group 5, <60 mL/min/1.73m².ResultsThe weighted anemia prevalence rates were 2.6% in men and 12.8% in women. In men, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked at an eGFR of 60–89 mL/min/1.73m² and decreased thereafter at an eGFR of <60 mL/min/1.73m² (15.19±0.03, 15.35±0.03, 15.53±0.03, 15.52±0.06, and 14.90±0.12 g/dL from Groups 1 to 5) after adjustment for age, college graduation, cancer history, current smoking, waist circumference, serum cholesterol level, serum triglyceride level, and diastolic blood pressure. In women, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked with an eGFR of 75–89 mL/min/1.73m² and decreased thereafter (12.90±0.03, 13.08±0.02, 13.20±0.04, 13.14±0.05, and 12.47±0.11 g/dL from Groups 1 to 5) after adjustment for menstruation, pregnancy, estrogen replacement, and the above-mentioned variables. In both sexes, the weighted prevalence of anemia with an eGFR of 60–104 mL/min/1.73m² was significantly lower than that with an eGFR of ≥105 mL/min/1.73m² (men, 3.2±0.4%, 1.9±0.3%, 1.8±0.3%, 2.0±0.9%, and 18.1±3.1%; women, 14.0±0.8%, 11.2±0.7%, 10.5±1.0%, 13.2±1.6%, and 32.3±3.2% from Groups 1 to 5).ConclusionsWe noted a compensatory increase in the hemoglobin level with a minor decline in kidney function (in the range of eGFR ≥60 mL/min/1.73m²) prior to a marked decrease in hemoglobin level with severe renal dysfunction.     

Serum Lipids in Cholelithiasis: Effect of Chenodeoxycholic Acid Therapy

Hypercholesterolaemia has been predicted as a possible complication of chenodeoxycholic acid treatment for gall stones. To exclude this, fasting serum lipids were measured in patients with stones before and at monthly intervals for six months after starting chenodeoxycholic acid. Before treatment half of a group of 36 patients with presumed cholesterol gall stones had serum cholesterol levels exceeding 260 mg/100 ml or serum triglyceride values greater than 160 mg/100 ml or both; these lipid levels were significantly greater than those in control subjects matched for age and sex. Treatment with chenodeoxycholic acid (0·5-1·5 g/day by mouth) did not change serum cholesterol levels but did significantly reduce serum triglyceride concentrations from a pretreatment level of 118 (± S.E. of mean 11·7) mg/100 ml to 95 (± 7·2) mg/100 ml after six months of therapy. The mechanism of this triglyceride-lowering action of chenodeoxycholic acid is not known, but it may have therapeutic value in patients with hypertriglyceridaemia.     

Estimation of Dietary Iron Bioavailability from Food Iron Intake and Iron Status

Currently there are no satisfactory methods for estimating dietary iron absorption (bioavailability) at a population level, but this is essential for deriving dietary reference values using the factorial approach. The aim of this work was to develop a novel approach for estimating dietary iron absorption using a population sample from a sub-section of the UK National Diet and Nutrition Survey (NDNS). Data were analyzed in 873 subjects from the 2000–2001 adult cohort of the NDNS, for whom both dietary intake data and hematological measures (hemoglobin and serum ferritin (SF) concentrations) were available. There were 495 men aged 19–64 y (mean age 42.7±12.1 y) and 378 pre-menopausal women (mean age 35.7±8.2 y). Individual dietary iron requirements were estimated using the Institute of Medicine calculations. A full probability approach was then applied to estimate the prevalence of dietary intakes that were insufficient to meet the needs of the men and women separately, based on their estimated daily iron intake and a series of absorption values ranging from 1–40%. The prevalence of SF concentrations below selected cut-off values (indicating that absorption was not high enough to maintain iron stores) was derived from individual SF concentrations. An estimate of dietary iron absorption required to maintain specified SF values was then calculated by matching the observed prevalence of insufficiency with the prevalence predicted for the series of absorption estimates. Mean daily dietary iron intakes were 13.5 mg for men and 9.8 mg for women. Mean calculated dietary absorption was 8% in men (50^th percentile for SF 85 µg/L) and 17% in women (50^th percentile for SF 38 µg/L). At a ferritin level of 45 µg/L estimated absorption was similar in men (14%) and women (13%). This new method can be used to calculate dietary iron absorption at a population level using data describing total iron intake and SF concentration.     

Serum Lipopolysaccharide Binding Protein Levels Predict Severity of Lung Injury and Mortality in Patients with Severe Sepsis

Background

There is a need for biomarkers insuring identification of septic patients at high-risk for death. We performed a prospective, multicenter, observational study to investigate the time-course of lipopolysaccharide binding protein (LBP) serum levels in patients with severe sepsis and examined whether serial serum levels of LBP could be used as a marker of outcome.

Methodology/Principal Findings

LBP serum levels at study entry, at 48 hours and at day-7 were measured in 180 patients with severe sepsis. Data regarding the nature of infections, disease severity, development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), and intensive care unit (ICU) outcome were recorded. LBP serum levels were similar in survivors and non-survivors at study entry (117.4±75.7 µg/mL vs. 129.8±71.3 µg/mL, P = 0.249) but there were significant differences at 48 hours (77.2±57.0 vs. 121.2±73.4 µg/mL, P<0.0001) and at day-7 (64.7±45.8 vs. 89.7±61.1 µg/ml, p = 0.017). At 48 hours, LBP levels were significantly higher in ARDS patients than in ALI patients (112.5±71.8 µg/ml vs. 76.6±55.9 µg/ml, P = 0.0001). An increase of LBP levels at 48 hours was associated with higher mortality (odds ratio 3.97; 95%CI: 1.84–8.56; P<0.001).

Conclusions/Significance

Serial LBP serum measurements may offer a clinically useful biomarker for identification of patients with severe sepsis having the worst outcomes and the highest probability of developing sepsis-induced ARDS.