Helicobacter pylori Infection: Clinical, Endoscopic, and Histological Findings in Lebanese Pediatric Patients.

BACKGROUND: Helicobacter pylori (H. pylori) is a common and universally distributed bacterial infection. However, in children, active gastritis and ulcer are rarely seen. OBJECTIVES: The aims of this study were to establish the prevalence of H. pylori infection and to compare the clinical, endoscopic, and histopathological findings between infected and noninfected pediatric patients at Makassed General Hospital. METHODS: Patients aged between 1 month and 17 years who underwent upper gastrointestinal endoscopy from January 2011 to January 2017 were included. The diagnosis of H. pylori was confirmed by a CLO test and/or its presence on biopsy specimens. Demographic data, clinical characteristics, endoscopic and histopathological findings, and gastritis score were recorded retrospectively. RESULTS: During the study period, 651 children underwent upper gastrointestinal endoscopy. The main indication was abdominal pain (61%). The prevalence of H. pylori infection was 16.5%. The infection was most commonly seen among children aged between 6 and 10 years (43%). A large number of family members were associated with increased risk of infection (4.8 ± 1.5 versus 5.2 ± 1.8; p < 0.05). Epigastric pain was more associated with H. pylori (61.3% versus 14.6% in noninfected patients; p < 0.05). Nodular gastritis was commonly seen in infected patients (41.5% vs. 7.9%; p < 0.05). Mild and moderate gastritis was seen more in infected versus noninfected patients (mild: 53.8% vs. 14%; moderate: 27.4% vs. 2.4%, respectively). CONCLUSION: Although epigastric pain was associated with H. pylori, other diagnoses should be considered since the infection are rarely symptomatic in children. Antral nodularity was associated with H. pylori infection; however, its absence does not preclude the diagnosis.

Ultrasound-triggered delivery of paclitaxel encapsulated in an emulsion at low acoustic pressures.

We investigated the in vitro ultrasound-triggered delivery of paclitaxel, a well known anti-cancerous drug, encapsulated in an emulsion and in the presence of CT26 tumor cells. The emulsion was made of nanodroplets, whose volume comprised 95% perfluoro-octyl bromide and 5% tributyl O-acetylcitrate, in which paclitaxel was solubilized. These nanodroplets, prepared using a high-pressure microfluidizer, were stabilized by a tailor-made and recently patented biocompatible fluorinated surfactant. The delivery investigations were performed at 37 °C using a high intensity focused ultrasound transducer at a frequency of 1.1 MHz. The ultrasonic pulse was made of 275 sinusoidal periods and the pulse repetition frequency was 200 Hz with a duty cycle of 5%. The measured viabilities of CT26 cells showed that paclitaxel delivery was achievable for peak-to-peak pressures of 0.4 and 3.5 MPa, without having to vaporize the perfluorocarbon part of the droplet or to induce inertial cavitation.

Plasma inflammatory cytokines and survival of pancreatic cancer patients.

OBJECTIVES: Inflammation and inflammatory conditions have been associated with pancreatic cancer risk and progression in a number of clinical, epidemiological, and animal model studies. The goal of the present study is to identify plasma markers of inflammation associated with survival of pancreatic cancer patients, and assess their joint contribution to patient outcome. METHODS: We measured circulating levels of four established markers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor type II (sTNF-RII), and macrophage inhibitory cytokine-1 (MIC-1)) in 446 patients enrolled in an ongoing prospective clinic-based study. Hazard ratios (HRs) and 95% confidence intervals (CI) for death were estimated using multivariate Cox proportional hazards models. RESULTS: Overall mortality was significantly increased in patients in the top quartile of CRP (HR = 2.52, 95% CI: 1.82-3.49), IL-6 (HR = 2.78, 95% CI: 2.03-3.81), sTNF-RII (HR = 2.00, 95% CI: 1.46-2.72), and MIC-1 (HR = 2.53, 95% CI: 1.83-3.50), compared to those in the bottom quartile (P-trend <0.0001 for all four comparisons). Furthermore, patients with higher circulating concentrations of all four cytokines had a median survival of 3.7 months; whereas, those with lower levels had a median survival of 19.2 months (HR = 4.55, 95% CI: 2.87-7.20, P-trend <0.0001). CONCLUSION: Individual elevated plasma inflammatory cytokines are associated with significant and dramatic reductions in pancreatic cancer patient survival. Furthermore, we observed an independent combined effect of those cytokines on patient survival, suggesting that multiple inflammatory pathways are likely involved in PDAC progression. Future research efforts to target the inflammatory state using combination strategies in pancreatic cancer patients are warranted.

The use of multiplex PCR for the diagnosis of viral severe acute respiratory infection in children: a high rate of co-detection during the winter season.

Respiratory tract infection is a major cause of hospitalization in children. Although most such infections are viral in origin, it is difficult to differentiate bacterial and viral infections, as the clinical symptoms are similar. Multiplex polymerase chain reaction (PCR) methods allow testing for multiple pathogens simultaneously and are, therefore, gaining interest. This prospective case-control study was conducted from October 2013 to February 2014. Nasopharyngeal (NP) and oropharyngeal (throat) swabs were obtained from children admitted with severe acute respiratory infection (SARI) at a tertiary hospital. A control group of 40 asymptomatic children was included. Testing for 16 viruses was done by real-time multiplex PCR. Multiplex PCR detected a viral pathogen in 159/177 (89.9 %) patients admitted with SARI. There was a high rate of co-infection (46.9 %). Dual detections were observed in 64 (36.2 %), triple detections in 17 (9.6 %), and quadruple detections in 2 (1.1 %) of 177 samples. Seventy-eight patients required intensive care unit (ICU) admission, of whom 28 (35.8 %) had co-infection with multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected among asymptomatic children. This study confirms the high rate of detection of viral nucleic acids by multiplex PCR among hospitalized children admitted with SARI, as well as the high rate of co-detection of multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected in asymptomatic children, resulting in challenges in clinical interpretation. Studies are required to provide quantitative conclusions that will facilitate clinical interpretation and application of the results in the clinical setting.

Towards microfluidic reactors for in situ synchrotron infrared studies.

Anodically bonded etched silicon microfluidic devices that allow infrared spectroscopic measurement of solutions are reported. These extend spatially well-resolved in situ infrared measurement to higher temperatures and pressures than previously reported, making them useful for effectively time-resolved measurement of realistic catalytic processes. A data processing technique necessary for the mitigation of interference fringes caused by multiple reflections of the probe beam is also described.

Can fetal pulmonary artery Doppler indices predict neonatal respiratory distress syndrome?

OBJECTIVE: To study whether fetal main pulmonary artery (MPA) Doppler indices can predict the development of neonatal respiratory distress syndrome (RDS). STUDY DESIGN: This prospective cross-sectional study included pregnant women between 34 and 38+6 weeks gestation. The diagnostic accuracy of MPA Doppler measurements (systolic/diastolic (S/D) ratio, peak systolic velocity (PSV), pulsatility index (PI), resistance index (RI) and acceleration time/ejection time (At/Et)) for diagnosis of neonatal RDS was tested. RESULT: Of the 698 eligible fetuses, 55 (7.87%) developed neonatal RDS. PSV, PI, RI and At/Et were positively correlated with gestational age. The strongest correlation was found with At/Et (r=0.602, P<0.001). PI and RI were significantly higher, whereas At/Et and PSV were significantly lower in fetuses that developed RDS. A cutoff value of 0.305 for At/Et predicted the development of RDS (sensitivity: 76.4%; specificity: 91.6%). CONCLUSION: Development of neonatal RDS can be predicted using the MPA At/Et with high sensitivity and specificity.

Plasma sex steroid hormones and risk of developing type 2 diabetes in women: a prospective study.

AIMS/HYPOTHESIS: Prospective data directly investigating the role of endogenous sex hormones in diabetes risk have been scant, particularly in women. We aimed to examine comprehensively plasma sex hormones in connection with risk of developing type 2 diabetes in postmenopausal women. METHODS: We conducted a prospective, nested case-control study of plasma oestradiol, testosterone and dehydroepiandrosterone sulfate and risk of type 2 diabetes in a cohort of women health professionals with a mean age of 60.3 and 12.2 years since menopause. Among women not using hormone therapy and free of baseline cardiovascular disease, cancer and diabetes, 359 incident cases of type 2 diabetes were matched with 359 controls during an average follow-up of 10 years. RESULTS: Oestradiol and testosterone were each strongly and positively associated with risk of type 2 diabetes. After adjustment for BMI, family history, lifestyle and reproductive variables, the multivariable relative risks (95% CI) comparing the highest vs lowest quintile were 12.6 (2.83-56.3) for total oestradiol (p = 0.002 for trend), 13.1 (4.18-40.8) for free oestradiol (p < 0.001 for trend), 4.15 (1.21-14.2) for total testosterone (p = 0.019 for trend) and 14.8 (4.44-49.2) for free testosterone (p < 0.001 for trend). These associations remained robust after adjusting and accounting for other metabolic syndrome components and baseline HbA(1c) levels. CONCLUSIONS/INTERPRETATION: In postmenopausal women, higher plasma levels of oestradiol and testosterone were strongly and prospectively related to increased risk of developing type 2 diabetes. These prospective data indicate that endogenous levels of sex hormones may play important roles in the pathogenesis of type 2 diabetes. ClinicalTrials.gov ID no.: NCT00000479.

Effects of testosterone therapy on cardiovascular risk markers in androgen-deficient women with hypopituitarism.

CONTEXT: Low-dose testosterone replacement therapy in women with relative androgen deficiency has been shown to have beneficial effects on body composition, bone mass, and psychosexual function. However, the safety of chronic testosterone administration on cardiovascular risk and insulin resistance is unknown. OBJECTIVE: The aim of the study was to determine the effects of physiological testosterone replacement on cardiovascular risk markers and insulin resistance in women. DESIGN: A 12-month, randomized, placebo-controlled study was conducted. SETTING: A General Clinical Research Center was the setting for the study. STUDY PARTICIPANTS: A total of 51 women of reproductive age with androgen deficiency due to hypopituitarism participated. INTERVENTION: Study participants were randomized to physiological testosterone administration, 300 mug daily, or placebo, by patch. MAIN OUTCOME MEASURES: We measured fasting glucose, fasting insulin, insulin-resistance homeostasis model of assessment (IRHOMA), quantitative insulin sensitivity check index (QUICKI), high-sensitivity C-reactive protein, vascular cell adhesion molecule (VCAM), leptin, lipoprotein (a), apolipoprotein A1, and homocysteine. RESULTS: At 12 months, fasting insulin and IRHOMA were significantly lower in the testosterone compared with the placebo group, and there was a trend toward a higher QUICKI level at 12 months in the testosterone compared with the placebo group. These differences were no longer significant after controlling for baseline levels. We observed no effect, either positive or negative, of testosterone administration on high-sensitivity C-reactive protein, VCAM leptin, lipoprotein (a), or apolipoprotein A1. CONCLUSIONS: Our data suggest that physiological testosterone replacement in women with hypopituitarism for 12 months does not increase, and may improve, insulin resistance. Chronic low-dose testosterone administration does not increase markers of cardiovascular disease reflecting several different mechanistic pathways. Large, randomized, placebo-controlled, long-term prospective studies are needed to determine whether low-dose testosterone replacement affects cardiovascular risk and event rates in women.

High-sensitivity C-reactive protein, adiposity, and blood pressure in the Yakut of Siberia.

C-reactive protein (CRP), an acute-phase reactant and marker of inflammatory response, is known to be an important predictor of future cardiovascular mortality, independent of other risk factors. The purpose of this research was to investigate the association between CRP, adiposity, and blood pressure in the Yakut, an indigenous Siberian population undergoing rapid cultural change. We conducted a cross-sectional study of 265 healthy Yakut adults in six villages in rural northeastern Siberia. Plasma CRP was measured by high-sensitivity immunoturbidimetric assay. The median CRP value was 0.85 mg/l, with values for the 25th, 50th, and 75th percentiles of 0.30, 0.85, and 2.28 mg/l, respectively. CRP was positively associated with age (r = 0.19; P = 0.002), but not plasma lipids or smoking status. CRP was associated with measures of central adiposity and characteristics of the metabolic syndrome, particularly in women. We found significantly higher CRP across quintiles (Q) of waist circumference for women (difference = 0.7 mg/l; P = 0.035), but not men (difference = 0.36 mg/l; P = 0.515). CRP was significantly associated with systolic blood pressure in men (difference, Q1 vs. Q5 = 1.1 mg/l; P = 0.044) but not women (difference, Q1 vs. Q5 = 0.03 mg/l; P = 0.713) after adjusting for age, waist circumference, and smoking status. CRP in the Yakut was considerably lower than was reported for other populations. The low CRP levels may be explained in part by a low prevalence of abdominal obesity. Among the Yakut, the high physical-activity demands of a traditional herding lifeway likely play a role through high energy expenditure and maintenance of negative energy balance. Our findings underscore the need for further research on the metabolic activity of adipose tissue, blood pressure, and inflammatory activation in non-Western populations.

Cross-sectional relations of serum aldosterone and urine sodium excretion to urinary albumin excretion in a community-based sample.

Experimental models suggest that increased aldosterone and sodium intake are associated with renovascular damage and resultant proteinuria. We hypothesized that serum aldosterone and urinary sodium would be associated with urinary albumin excretion, an indicator of kidney damage. We evaluated 2700 participants (53% women, mean age 58 years) from the Framingham Offspring Study who attended a routine examination between 1995 and 1998, who were free of heart failure and renal failure, and underwent testing for serum aldosterone, spot urinary sodium, and urinary albumin excretion (urine albumin/creatinine ratio, UACR), the latter two indexed to urinary creatinine. Stepwise multivariable linear regression was used to evaluate the relations between UACR with urinary sodium index and serum aldosterone. In multivariable regression, log urinary sodium index was associated positively with log-UACR (P<0.0001). UACR levels in the fourth and fifth quintiles of urinary sodium index were 24% (95% confidence interval (CI) 3-49%), and twofold higher (95% CI 72-150%), respectively, relative to the lowest quintile (P-value for trend across quintiles <0.001). In multivariable models, log-transformed aldosterone was not related to log-UACR. The top quintile of serum aldosterone levels was associated with a 21% higher (95% 1-44%) UACR levels relative to the lowest quintile. Urinary albumin excretion was strongly and positively associated in a continuous fashion with urinary sodium excretion, whereas a weaker nonlinear positive relation with serum aldosterone was noted. Our cross-sectional observations raise the possibility that dietary salt intake may be associated with early renovascular damage.

Increased inflammatory markers in children with familial hypercholesterolaemia.

BACKGROUND: While data are abundant on increased levels of inflammatory markers in adult patients with hypercholesterolaemia, such data in children are limited. Therefore, we sought to investigate the degree and character of inflammation in children with heterozygous familial hypercholesterolaemia (FH) by measuring levels of neopterin, high-sensitivity C-reactive protein (hsCRP), and soluble CD40 ligand (sCD40L). MATERIALS AND METHODS: In the present study, we compared the concentration of inflammatory markers in children suffering from heterozygous FH (n = 207) with those in unaffected siblings (n = 84). Furthermore, we investigated the effect of 2-year treatment with pravastatin (20-40 mg qd) or placebo on plasma levels of those markers. RESULTS: Our main finding was that serum levels of neopterin and hsCRP were significantly higher in FH children compared with healthy siblings, whereas sCD40L was not. Body mass index and high-density lipoprotein cholesterol levels were significant independent predictors of hsCRP and neopterin. Furthermore, pravastatin therapy decreased neopterin, but not hsCRP and sCD40L, in the FH children, but these changes were not different from the placebo group. CONCLUSION: These findings indicate low-grade monocyte/macrophage hyperactivity in the early stages of atherogenesis, but our findings also suggest that inflammation as well as anti-inflammatory effects of statins are less prominent features of atherosclerosis in FH children than in FH adults.

The association of serum lipids and inflammatory biomarkers with renal function in men with type II diabetes mellitus.

Dyslipidemia and inflammation may promote renal disease via mechanisms of vascular endothelial cell dysfunction in type II diabetes mellitus (DM). Sparse data, however, are available on the relation of lipids and inflammatory biomarkers and glomerular filtration rate (GFR) in type II DM. We performed a cross-sectional study of 732 men with type II DM enrolled in the Health Professionals' Follow-Up Study. Plasma creatinine was used to estimate GFR by the simplified Modification of Diet in Renal Disease (MDRD) equation. In men with a GFR <60 ml/min/1.73 m(2), triglycerides, non-high-density lipoprotein (HDL), apoprotein B, fibrinogen, soluble tumor necrosis factor receptor (sTNFR-2) and vascular cell adhesion molecule-1 (VCAM) were significantly higher when compared to the referent group (GFR> or =90 ml/min/1.73 m(2)). In multivariable logistic regression, those in the highest quartiles of the following biomarkers had increased odds of having a GFR <60 ml/min/1.73 m(2) when compared to those in the lowest quartiles: triglycerides (odds ratio (OR) 3.11; 95% CI, 1.52-6.36), fibrinogen (OR 5.40; 95% CI 2.14-13.65), sTNFR-2 (OR 8.34; 95% CI 3.50-19.88) and VCAM (OR 4.50; 95% CI 1.98-10.23). An inverse association was observed for HDL (OR 0.48; 95% CI 0.24-0.98). We found no association between C-reactive protein and GFR. The results were similar when creatinine clearance by Cockcroft-Gault was used to estimate kidney function. We conclude that several potentially modifiable lipid and inflammatory biomarkers are elevated in the setting of moderately decreased GFR in men with type II DM and may be the link between renal insufficiency and increased risk for cardiovascular events in this population.

Tandem mass spectrometry method for the quantification of serum busulfan.

Busulfan, an alkylating agent, is most commonly used as a component of bone marrow transplantation preoperative regimens. Significant interpatient and intrapatient variations in pharmacokinetics require individualizing the dosage based on area under the time-versus-concentration curve. Timely result reporting is critical to dose adjustment to reduce morbidity and mortality associated with the regimen. The authors developed a rapid, accurate, and sensitive method for the quantification of serum busulfan using direct inject tandem mass spectrometry. Plasma samples (50 microL) are extracted in 1 mL of methanol containing 1,6-bis-(methanesulfonyloxy)hexane as an internal standard. The supernatant is dried under nitrogen (40 degrees C, 30 minutes) and then dissolved in 200 microL methanol and transferred into a clean glass vial suitable for LC/MS/MS analysis. The sample is delivered using an HPLC pump that delivers 0.2 mL of methanol per minute, and 20 microL of sample is injected into a turbo ion spray-equipped tandem mass spectrometer. Total analysis time is 5 minutes. The Q1/Q3 transition for busulfan (BU) is monitored at 269/55 and 297.1/55.1 for the internal standard. The assay is linear to 10 micromol/L and sensitive to at least 0.5 micromol/L. The interassay reproducibility at 1, 2.2, and 4.4 micromol/L were 4.2%, 5.6%, and 6.3%, respectively. Within-run precision using 3 different control samples was 3.9%, 3.9%, and 6.9%. Mean recovery of 4 different BU concentrations spiked into 10 different BU free plasma samples was 98%. Correlation with an established HPLC-UV method revealed a slope of 0.98, an intercept of 0.1, and r = 0.95 (n = 48). No significant interfering substances or ion suppression was identified. This method is a significant improvement over the existing HPLC-UV method for BU determination. The method is highly accurate, reproducible, and requires less specimen, sample preparation, and analysis time.

Hyperproinsulinaemia and risk of Type 2 diabetes mellitus in women.

AIMS: Our objective was to examine prospectively the associations between fasting plasma proinsulin and the proinsulin/insulin ratio and the incidence of Type 2 diabetes in women. SUBJECTS AND METHODS: We designed a nested case-control study within the Nurses' Health Study, a cohort of 121,700 US women aged 30-55 years at study inception in 1976. Fasting plasma proinsulin, specific insulin and C-peptide levels were determined in 183 women with a new diagnosis of diabetes made after blood sampling between 1989 and 1990, and 369 control subjects without diabetes. RESULTS: After adjustment for age, body mass index, family history of diabetes and other potential confounders, including HbA1c, the odds ratios for diabetes associated with increasing quartiles of proinsulin were 1.00, 0.85, 2.49 and 5.73 (P for trend: < 0.001). Proinsulin remained significantly associated with diabetes risk after adjusting for C-peptide and specific insulin (multivariate odds ratios for quartiles: 1.00, 0.78, 1.94, 3.69; P for trend = 0.001). In addition, the proinsulin/insulin ratio was significantly associated with diabetes risk, controlling in multivariate analysis for C-peptide (odds ratios for extreme quartiles: 2.48; 95% CI: 1.14-5.41; P for trend = 0.005). CONCLUSIONS: These data suggest that proinsulin and the proinsulin/insulin ratio are strong independent predictors of diabetes risk, after adjustment for obesity and other potential confounders.

Selenium levels in relation to morbidity and mortality among children born to HIV-infected mothers.

OBJECTIVE: To examine the relation between selenium status and child mortality and morbidity among children born to HIV-infected mothers. DESIGN: Prospective cohort study. METHODS: Study participants were originally part of a trial to study the effect of maternal vitamin supplements on maternal and child health outcomes. Morbidity information was collected during monthly clinic visits until the child reached 24 months of age. Out of 984 livebirths, 806 had morbidity information, and 610 also had data on plasma selenium levels available. SETTING: A study clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania, a tertiary-care hospital. RESULTS: The median age at baseline was 10.5 weeks. A total of 117 (19%) of the 610 study children died during follow-up. In a multivariate model, child plasma selenium levels were inversely associated with risk of all-cause mortality (P-value, test for trend=0.05). Plasma selenium levels were not significantly associated with risk of diarrhea or respiratory outcomes. CONCLUSIONS: Among infants born to HIV-infected women in sub-Saharan Africa, selenium status may be important to prevent child mortality. These preliminary findings warrant future reexamination.

A prospective study of lipoprotein(a) and risk of coronary heart disease among women with type 2 diabetes.

AIMS: We examined the association between lipoprotein (Lp)(a) and CHD among women with type 2 diabetes. METHODS: Of 32,826 women from the Nurses' Health Study who provided blood at baseline, we followed 921 who had a confirmed diagnosis of type 2 diabetes. RESULTS: During 10 years of follow-up (6,835 person-years), we documented 122 incident cases of CHD. After adjustment for age, smoking, BMI, glycosylated HbA(1)c, triglycerides (TGs), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and other cardiovascular risk factors, the relative risk (RR) comparing extreme quintiles of Lp(a) was 1.95 (95% CI 1.07-3.56). The association was not appreciably altered after further adjustment for apolipoprotein B(100) or several inflammatory biomarkers. Increasing levels of Lp(a) were associated with lower levels of TGs. The probability of developing CHD over 10 years was higher among diabetic women with substantially higher levels of both Lp(a) (>1.07 micromol/l) and TGs (>2.26 mmol/l) than among diabetic women with lower levels (22 vs 10%, p log-rank test=0.049). Diabetic women with a higher level of only Lp(a) or TGs had a similar (14%) risk. In a multivariate model, diabetic women with higher levels of Lp(a) and TGs had an RR of 2.46 (95% CI 1.21-5.01) for developing CHD, as compared with those with lower levels of both biomarkers (p for interaction=0.413). The RRs for women with a higher level of either Lp(a) (RR=1.22, 95% CI 0.77-1.92) or TGs (RR=1.39, 95% CI 0.78-2.42) were comparable. CONCLUSIONS/INTERPRETATION: Increased levels of Lp(a) were independently associated with risk of CHD among diabetic women.

Effect of vitamin supplementation to HIV-infected pregnant women on the micronutrient status of their infants.

OBJECTIVE: We examined whether supplementation with vitamin A and/or vitamins B, C, and E to HIV-infected women during pregnancy and lactation is related to increased concentrations of vitamins A, B12, and E in their infants during the first 6 months of life. DESIGN: We carried out a randomized clinical trial among 716 mother-infant pairs in Dar-es-Salaam, Tanzania. Women were randomly allocated to receive a daily oral dose of one of four regimens: vitamin A, multivitamins (B, C, and E), multivitamins including A, or placebo. Supplementation started at first prenatal visit and continued after delivery throughout the breastfeeding period. The serum concentration of vitamins A, E and B12 was measured in infants at 6 weeks and 6 months postpartum. RESULTS: Maternal vitamin A supplementation increased serum retinol in the infants at 6 weeks (mean difference=0.09 micromol/l, P<0.0001) and 6 months (mean difference=0.06 micromol/l, P=0.0002), and decreased the prevalence of vitamin A deficiency, but had no impact on serum vitamins E or B12. Multivitamins increased serum vitamin B12 at 6 weeks and 6 months (mean differences=176 pmol/l, P<0.0001 and 127 pmol/l, P<0.0001, respectively) and vitamin E (mean differences=1.8 micromol/l, P=0.0008 and 1.1 micromol/l, P=0.004, respectively) and decreased the prevalence of vitamin B12 deficiency. CONCLUSIONS: Vitamin supplementation to HIV-1-infected women is effective in improving the vitamin status of infants during the first 6 months of age.

Truncal adiposity, relative growth hormone deficiency, and cardiovascular risk.

We hypothesized that endogenous GH would be reduced in healthy women with relative truncal adiposity despite lack of generalized obesity and that decreased GH would be associated with increased cardiovascular risk markers. Fifteen healthy female volunteers were divided into two groups, low truncal fat and high truncal fat, of comparable body mass index (BMI). Age and BMI (23.7 +/- 2.1 vs. 25.8 +/- 2.8 kg/m(2)) were similar in the two groups. Trunk fat was higher in the high-truncal-fat group, as designed. Twenty-four-hour mean GH, amplitude, and basal GH concentration were 41, 32, and 36% lower, respectively, in the high-truncal-fat group, but GH pulse frequency and IGF-I levels did not differ. In a stepwise regression model, trunk fat accounted for 38% of the variation of mean GH levels (P = 0.02), but neither total body fat nor BMI were significant determinants of mean GH in the model. There was a strong inverse association between mean 24-h GH and both truncal fat and cardiovascular risk markers, including high-sensitivity C-reactive protein. Our data suggest that visceral adiposity may be associated with reduced endogenous GH in healthy women, even in the absence of generalized obesity, and that decreased GH secretion may be associated with increased cardiovascular risk markers in this population.

Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study.

OBJECTIVE: The primary objective of this study was to determine whether the National Cholesterol Education Program Step II (NCEP-II) diet or supplementation with docosahexaenoic acid (DHA) with the diet, affects endothelial function in children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). As secondary endpoints, the influence of diet and DHA supplementation on lipid profiles as well as biomarkers for oxidative stress and inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, were all evaluated. METHODS: In a double-blind, placebo-controlled, randomized, crossover study design, 20 children (ages 9-19 years) with FH (n = 12) and FCH (n = 8) received nutritional counseling based on the National Cholesterol Education Program Step II (NCEP-II) and food guide pyramid dietary guidelines for 6 weeks. They were then randomly assigned to supplementation with docosahexaenoic acid (DHA 1.2 g/d) or placebo for 6 weeks, followed by a washout phase of 6 weeks and crossover phase of 6 weeks while continuing the NCEP-II diet. Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery was determined by high-resolution ultrasound. Plasma levels of total cholesterol, triglycerides and lipoprotein classes (LDL, HDL, VLDL) were measured by ultracentrifugation and enzymatic methods, plasma F2 isoprostanes by gas chromatography/mass spectrometry, urinary 8-OH-2' deoxyguanosine by liquid chromatography, high sensitivity C-reactive protein by immunonephelometry and ADMA by liquid chromatography. RESULTS: FMD increased significantly after DHA supplementation compared to baseline (p < 0.001), diet alone (p < 0.002), placebo (p < 0.012) and washout (p < 0.001) phases of the study without affecting biomarkers for oxidative stress, inflammation or ADMA. DHA supplementation was associated with increased levels of total cholesterol (p < 0.01), LDL- and HDL cholesterol concentrations (p < 0.001) compared to the NCEP-II diet. CONCLUSION: This study demonstrates that DHA supplementation restores endothelial-dependent FMD in hyperlipidemic children. The endothelium may thus be a therapeutic target for DHA. This is consistent with a hypothesis of increasing NO bioavailability, with the potential for preventing the progression of early coronary heart disease in high-risk children.

Moderate alcohol intake and markers of inflammation and endothelial dysfunction among diabetic men.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus is characterised by heightened inflammation and endothelial dysfunction. Moderate alcohol intake has been associated with a reduced risk of cardiovascular disease in type 2 diabetic patients. It remains to be determined whether there is an association between alcohol and inflammation in individuals with diabetes. METHODS: We investigated the relationship between alcohol intake and inflammation in 726 of 18,159 men who returned blood samples in the Health Professionals Follow-up Study and had confirmed type 2 diabetes at blood draw. RESULTS: In age-adjusted analyses, alcohol intake was associated with lower levels of HbA1c, fibrinogen, soluble tumour necrosis factor receptor-2 (sTNF-R2) and soluble vascular adhesion molecule-1 (sVCAM-1), and with higher levels of HDL cholesterol and adiponectin (p value for trends <0.05). After adjustment for age, HbA1c, insulin use, fasting status, smoking, BMI, physical activity, aspirin use, prevalence of cardiovascular disease and dietary factors, each additional drink per day was related to increased HDL cholesterol (0.053 mmol/l, p<0.0001) and adiponectin (0.8 microg/ml, p=0.01), and decreased sTNFR-2 (73 pg/ml, p=0.03), fibrinogen (0.302 micromol/l, p=0.02) and sVCAM-1 (33 ng/ml, p=0.02). The relationship between alcohol and inflammatory biomarkers persisted when subjects were stratified according to HbA1c levels. CONCLUSIONS/INTERPRETATION: Moderate alcohol intake may have a beneficial effect on markers of inflammation and endothelial dysfunction in type 2 diabetic patients.