Vijaylaxmi Grey

Prevalence of Low Bone Mass and Deficiencies of Vitamins D and K in Pediatric Patients With Cystic Fibrosis From 3 Canadian Centers

OBJECTIVE. In this cross-sectional observational study, we assessed both vitamins D and K status and bone health in pancreatic insufficient pediatric patients with cystic fibrosis from 3 Canadian cystic fibrosis centers. METHODS. Eighty-one patients who had cystic fibrosis and were clinically stable for at least 3 months were enrolled. At the time of the clinic visit, anthropometric variables, lung function, pubertal status, intake of calcium and vitamins D and K, and physical activity were assessed. Blood was taken for analysis of biochemical biomarkers of bone turnover and status of vitamins D and K, and a urine sample was obtained for calcium, creatinine, sodium, and deoxypyridoline analyses. Whole-body bone mineral content and lumbar spine (L1–L4) bone mineral density were measured. RESULTS. The children were relatively well nourished and had moderate to mild lung disease. Low bone mineral mass defined as a z score between −1.0 and −2.0, for gender and age was detected in 38% of the children for whole body and in 28% for lumbar spine. z score less than −2.0 was observed in 7 children for both bone measures. Suboptimal vitamin D status occurred in 95% of patients; suboptimal vitamin K status occurred in 82% of patients. Measures of plasma osteocalcin and carboxy-terminal propeptide type 1 procollagen and urinary deoxypyridoline compared with reference values for age, gender, and pubertal status reflected a state of suppressed bone formation and elevated bone resorption in a large proportion of the patients. CONCLUSIONS. Bone mass of the whole body and spine was lower than expected for chronological age in approximately one third of pediatric patients with cystic fibrosis irrespective of gender or age. This may be explained by the observation of low bone turnover for developmental stage as indicated by bone biomarkers. Suboptimal status of vitamins D and K may be key causative factors of the low bone status for age.

Establishment of reference intervals for bone markers in children and adolescents.

OBJECTIVES To determine age and gender specific reference intervals for bone markers. DESIGN AND METHODS Morning blood samples were collected after overnight fast from 356 healthy children (6 to 18 year-old) for the determination of bone marker levels, PTH and vitamin D(3). Multiple regression analysis was done to assess the effect of factors that could influence the bone marker levels; the central 95% reference interval and their 90% CI were calculated. RESULTS After excluding samples when BMI-z -scores were <-2 or >+2, both vitamin D(3) and PTH levels were abnormal and from children who used steroids the remainder were partitioned using Tanner stage based chronological age. As expected the reference intervals show a significant variation with age and gender. All the bone marker levels, except total alkaline phosphatase, were significantly higher in puberty with vitamin D(3) >75nmol/L. CONCLUSION Vitamin D status, age and gender are important for establishing reference intervals of bone markers in healthy children.

An open-label dose–response study of lymphocyte glutathione levels in healthy men and women receiving pressurized whey protein isolate supplements

Background High-pressure treatment of whey protein may increase digestibility and bioavailability of cysteine. The purpose of the study was to determine whether total lymphocyte glutathione (γ-glutamyl-cysteinyl-glycine [GSH]) levels (oxidized+reduced) can be augmented from three different doses of pressurized whey protein supplements in a dose-dependent manner over a 2-week period. Methods Eighteen healthy males and 18 healthy females were randomized into three different groups, with 31 finishing the study. Each group ingested 15, 30, or 45 g/day pressurized whey protein in the morning in bar format for 14 days. Each group was blinded to the amount of whey protein they were ingesting. Ten millilitres of blood was withdrawn before and after the 2-week period to assess blood lymphocyte levels pre and post supplementation. Results There was no change in body weight or reported physical activity levels pre and post supplementation. Pre-lymphocyte GSH levels were not significantly different between groups (3.7±0.7µmol/l). Least-squares linear regression showed that the change in lymphocyte GSH levels from pre to post supplementation was affected by the amount of whey protein ingested daily (P=0.037). The group that ingested 45 g/day pressurized whey protein augmented GSH levels the most (by ∼24%), and the group that ingested 15 g/day did not increase lymphocyte GSH levels. Conclusions We conclude that there is a significant relationship between the dosage of supplementation and the change in lymphocyte GSH levels. Furthermore, the increase in GSH was linear with the amount of whey protein ingested. Pressurized whey protein supplementation of 45 g/day for 2 weeks can increase lymphocyte GSH by 24%.

Screening for hypoglycemia at the bedside in the neonatal intensive care unit (NICU) with the Abbott PCx glucose meter

BackgroundPoint of care (POC) glucose meters are routinely used as a screening tool for hypoglycemia in a neonatal setting. Glucose meters however, lack the same accuracy as laboratory instruments for glucose measurement. In this study we investigated potential reasons for this inaccuracy and established a cut off value for confirmatory testing.MethodsIn this prospective study, all patients in the neonatal intensive care unit who had a plasma glucose test ordered were eligible to participate. Demographic information, sample collection information (nine variables) and a recent hematocrit value were recorded for each sample. Glucose measurements were taken at the bedside on the glucose meter (RN PCx) as well as in the laboratory on both the glucose meter (LAB PCx) and the laboratory analyzer (PG). Data were analyzed by simple and mixed-effects regression analysis and by analysis of a receiver operator characteristics (ROC) curve.ResultsThere were 475 samples analyzed from 132 patients. RN PCx values were higher than PG values (mean = 4.9%), while LAB PCx results were lower (mean = -5.2%) than PG values. Only 31% of the difference between RN PCx – PG and 46% of the difference for LAB PCx – PG could be accounted for by the variables tested. The largest proportion of variance between PCx and PG measurements was explained by hematocrit (about 30%) with a greater effect seen at glucose concentrations ≤4.0 mmol/L (≤72 mg/dL)(48% and 40% for RN PCx and LAB PCx, respectively). The ROC analysis showed that for detection of all cases of hypoglycemia (PG < 2.6 mmol/L)(PG < 47 mg/dL) the PCx screening cut off value would need to be set at 3.8 mmol/L (68 mg/dL) requiring 20% of all samples to have confirmatory analysis by the laboratory method.ConclusionThe large difference between glucose results obtained by PCx glucose meter compared to the laboratory analyzer can be explained in part by hematocrit and low glucose concentration. These results emphasize that the glucose meter is useful only as a screening device for neonatal hypoglycemia and that a screening cut off value must be established.

Monitoring of 25-OH vitamin D levels in children with cystic fibrosis

BACKGROUND Patients with cystic fibrosis are at risk for malabsorption of fat-soluble vitamins, and those with low 25-OH vitamin D levels have a higher risk of low bone mineral density and long-term skeletal complications. It is currently recommended that vitamins A and E be monitored yearly; however, no recommendations exist for 25-OH vitamin D. Because all three vitamins are fat-soluble, the hypothesis in the current study was that low levels of vitamins A and E could identify patients at risk for low 25-OH vitamin D, so that 25-OH vitamin D measurements could be obtained in only selected circumstances. METHODS Forty (21 girls) patients with CF, age 10.5 +/- 3.9 (SD) years, were assessed in a cross-sectional survey for ideal weight for height (percentage of predicted), spirometry (percentage of predicted FEV1, 33/40 patients), and serum levels of vitamins A, E, 25-OH vitamin D, and cholesterol (37/40 patients). RESULTS Nine (22.5%) of 40 patients were malnourished (percentage of predicted ideal weight for height <85%), 7 (21.2%) of 33 had moderate to severe lung disease (FEV1 <60%), 4 (10%) of 40 had low levels of vitamin A, 3 (7.5%) of 40 had low vitamin E levels, 4 (10.8%) of 37 low vitamin E/cholesterol levels, and 4 (10%) of 40 had marginal or low levels of 25-OH vitamin D (<40 mmol/l). The patients with low 25-OH vitamin D were older, with no child < 12 years of age having a 25-OH vitamin D level less than 40 mmol/l. They also had lower vitamin E and vitamin E/cholesterol levels than those with normal 25-OH vitamin D levels. The groups did not differ in percentage of predicted ideal weight for height, lung function, or vitamin A levels. The best positive predictor for 25-OH vitamin D less than 40 mmol/l was low vitamin E (66.7%), with a negative predictive value of 94.6%. 25-OH vitamin D levels correlated with vitamin E/cholesterol levels (r = 0.41, P < 0.01) and weakly with vitamin E levels (r = 0.28, P < 0.08), but not with vitamin A levels. CONCLUSIONS These results suggest that children aged less than 12 years and older children with normal vitamin E levels are especially unlikely to have low 25-OH vitamin D levels, and this measure can therefore be omitted. In contrast, those children with low vitamin E levels may warrant monitoring.

Missed follow-up opportunities using a two-step screening approach for gestational diabetes

A 1-step approach for gestational diabetes (GDM) screening using a 75 g-oral glucose tolerance test (75 g-OGTT) has been recommended. We undertook an audit (January 2007-June 2010) to assess adherence to an existing 2-step approach (50 g-glucose challenge test followed by a 75 g-OGTT). Adherence was sub-optimal. Overall follow-up was missed in 14.5% of those screened. Only 36% of those who met dysglycemia criteria for a follow-up 75 g-OGTT received the test as per step 2 of the protocol.

Effect of whey protein to modulate immune response in children with atopic asthma.

Background Levels of glutathione (GSH) in antigen-presenting cells promote a T-helper type 2 (Th2) cytokine response in mice. We have previously demonstrated that we can increase intracellular GSH levels in healthy young adults using a whey-based oral supplement (HMS90™). We hypothesized that such supplementation in children with atopic asthma, a Th2 cytokine disease, would improve lung function and decrease atopy. Methods Eleven children (six females, five males; mean±standard deviation age, 12.6±3.6 years; baseline forced expired volume in 1 sec (FEV1), 82.4±15.4%predicted), underwent spirometry, methacholine provocation testing, and blood analysis for serum IgE and lymphocyte GSH before and after 1 month of supplementation (10 g twice daily). Results Initially the IgE was 1689±1596 µg/l (normal range ≤240 µg/l) and lymphocyte GSH was 1.75±0.48 µM (normal range 1.55±0.33 µM). IgE significantly decreased to 1379±1329 µg/l (P < 0.05) following supplementation. Although no significant changes in lymphocyte GSH or FEV1 were found for the group as a whole, the two patients with significant increases in lymphocyte GSH concentrations were the only two to demonstrate reductions in methacholine provocation doses (provocative concentration causing a 20% fall in FEV1). Conclusions These results suggest a modest impact of whey protein supplementation on the cytokine response in atopic asthma. Supplementation for longer periods, or with more potent whey-based supplements, currently under development, may prove more beneficial.

Pediatric critical values: laboratory-pediatrician discourse.

OBJECTIVES To review pediatric critical values after consultation with departmental pediatricians. METHODS An electronic survey with the critical value list of 26 high or low abnormal chemistry laboratory values of 12 analytes was circulated to pediatricians. The survey results were presented to a focus group of 3 pediatricians for comments and review. RESULTS Thirty-one of 125 pediatricians affiliated with the Department of Pediatrics responded. Sixteen of 26 (61.5%) current values met the agreement criteria. The procedures for calling high glucose levels in neonates and children, and the low magnesium and low ionized calcium critical values were revised after discussion with the focus group. CONCLUSIONS This survey among the hospitals pediatricians resulted not only in a revised list of critical values, but also the procedure for calling the user. The use of unique critical values for different areas of clinical practice within the childrens hospital was identified as an area for future development.