A 250 µg/week dose of vitamin D was as effective as a 50 µg/d dose in healthy adults, but a regimen of four weekly followed by monthly doses of 1250 µg raised the risk of hypercalciuria.

The risk of vitamin D insufficiency is increased in persons having limited sunlight exposure and dietary vitamin D. Supplementation compliance might be improved with larger doses taken less often, but this may increase the potential for side effects. The objective of the present study was to determine whether a weekly or weekly/monthly regimen of vitamin D supplementation is as effective as daily supplementation without increasing the risk of side effects. Participants were forty-eight healthy adults who were randomly assigned for 3 months to placebo or one of three supplementation regimens: 50 µg/d (2000 IU/d, analysed dose 70 µg/d), 250 µg/week (10 000 IU/week, analysed dose 331 µg/week) or 1250 µg/week (50 000 IU/week, analysed dose 1544 µg/week) for 4 weeks and then 1250 µg/ month for 2 months. Daily and weekly doses were equally effective at increasing serum 25-hydroxyvitamin D, which was significantly greater than baseline in all the supplemented groups after 30 d of treatment. Subjects in the 1250 µg treatment group, who had a BMI >26 kg/m2, had a steady increase in urinary Ca in the first 3 weeks of supplementation, and, overall, the relative risk of hypercalciuria was higher in the 1250 µg group than in the placebo group (P=0·01). Although vitamin D supplementation remains a controversial issue, these data document that supplementing with ≤ 250 mg/week (≤ 10 000 IU/week) can improve or maintain vitamin D status in healthy populations without the risk of hypercalciuria, but 24 h urinary Ca excretion should be evaluated in healthy persons receiving vitamin D3 supplementation in weekly single doses of 1250 µg (50 000 IU).

Growth assessment in clinical practice: whose growth curve?

Differences in growth curves can influence the diagnosis of under- and overnutrition, and the interpretation of adequate growth following nutrition intervention. This effect is notable when comparing the World Health Organization (WHO) 2006 Growth Standard and the Centers for Disease Control and Prevention (CDC) 2000 Growth Reference for infants and children to 59 months of age. Important differences relate to conceptual approaches for generating growth standards to describe what population growth should be, compared to a reference of what growth is. WHO included only term infants exclusively or predominantly breast-fed beyond 4 months, and data for infants and children indicative of excess adiposity and growth failure were removed. Thus, fewer children are diagnosed with poor weight gain, and more with excess adiposity, using the WHO Growth Standard than when using the CDC Growth Reference. Adequate growth is based on proportional height and weight gains that track along growth curve trajectories. Use of the WHO curves should assist in prevention of inappropriate intervention or overfeeding in young children.

The impact of a fast track area on quality and effectiveness outcomes: a Middle Eastern emergency department perspective.

BACKGROUND: Emergency department (ED) overcrowding is a ubiquitous problem with serious public health implications. The fast track area is a novel method which aims to reduce waiting time, patient dissatisfaction and morbidity. |The study objective was to determine the impact of a fast track area (FTA) on both effectiveness measures (i.e. waiting times [WT] and length of stay [LOS]) and quality measures (i.e. LWBS rates and mortality rates) in non-urgent patients. The secondary objective was to assess if a FTA negatively impacted on urgent patients entering the ED. METHODS: The study took place in a 500 bed, urban, tertiary care hospital in Abu Dhabi, United Arab Emirates. This was a quasi-experimental, which examined the impact of a FTA on a pre-intervention control group (January 2005) (n = 4,779) versus a post-intervention study group (January 2006) (n = 5,706). RESULTS: Mean WTs of Canadian Triage Acuity Scale (CTAS) 4 patients decreased by 22 min (95% CI 21 min to 24 min, P < 0.001). Similarly, mean WTs of CTAS 5 patients decreased by 28 min (95% CI 19 min to 37 min, P < 0.001) post FTA. The mean WTs of urgent patients (CTAS 2/3) were also significantly reduced after the FTA was opened (P < 0.001). The LWBS rate was reduced from 4.7% to 0.7% (95% CI 3.37 to 4.64; P < 0.001). Opening a FTA had no significant impact on mortality rates (P = 0.88). CONCLUSION: The FTA improved ED effectiveness (WTs and LOS) and quality measures (LWBS rates) whereas mortality rate remained unchanged.

Hepatic cirrhosis, dystonia, polycythaemia and hypermanganesaemia--a new metabolic disorder.

We report a new constellation of clinical features consisting of hypermanganesaemia, liver cirrhosis, an extrapyramidal motor disorder and polycythaemia in a 12 year-old girl born to consanguineous parents. Blood manganese levels were >3000 nmol/L (normal range <320 nmol/L) and MRI revealed signal abnormalities of the basal ganglia consistent with manganese deposition. An older brother with the same phenotype died at 18 years, suggesting a potentially lethal, autosomal recessive disease. This disorder is probably caused by a defect of manganese metabolism with the accumulation of manganese in the liver and the basal ganglia similar to the copper accumulation in Wilson disease. In order to assess the genetic basis of this syndrome we investigated two candidate genes: ATP2C2 and ATP2A3 encoding the manganese-transporting calcium-ATPases, SPCA2 and SERCA3, respectively. Genotyping of the patient and the family for microsatellite markers surrounding ATP2C2 and ATP2A3 excluded these genes. The patient was found to be heterozygous for both gene loci. Despite the unknown pathophysiology, we were able to develop a successful treatment regime. Chelation therapy with disodium calcium edetate combined with iron supplementation is the treatment of choice, lowering blood manganese levels significantly and improving clinical symptoms.

Nutritional rickets and z scores for height in the United Arab Emirates: to D or not to D?

BACKGROUND: Vitamin D deficiency is still prevalent worldwide, including the Middle East. A cohort of patients with nutritional rickets was treated with vitamin D(2) (ergocalciferol) alone. After this intervention, patients were followed to document changes in z scores for height after treatment. The secondary aim was to determine the proportion of affected children who had vitamin D deficiency or calcium deficiency. METHODS: Z score for height was calculated as the difference between the observed value and the median value, divided by the SD of the population. Z scores were compared in patients before and after treatment. RESULTS: The improvement in z score after treatment was 0.86 +/- 0.95. The 95% confidence interval for the mean difference was 1.32-0.40 (t = 3.95, P < 0.001). With a diagnostic cut-off for 25 hydroxyvitamin D(3) (25D) deficiency of <25 nmol/L, only half were diagnosed with severe vitamin D deficiency. The remaining patients had presumable calcium deficiency. The alkaline phosphatase (ALP) was negatively correlated to z scores, implying that higher ALP concentrations predicted severe bone disease (lower z scores). The variables 25D and age were moderately and positively correlated (Pearson's r = 0.59, 95%CI: 0.15-0.84; P = 0.01), indicating that younger infants had the lowest 25D levels. CONCLUSION: Vitamin D alone was efficient in resolving radiological and biochemical disturbances as well as improving z scores for height in a cohort of children with nutritional rickets, which included patients with 25D deficiency as well as calcium deficiency. The results support the hypothesis of the interplay and continuum of 25D deficiency and calcium deficiency in the pathogenesis of rickets.

Childhood seroprevalence of hepatitis A in the United Arab Emirates.

The seroprevalence of hepatitis A in Emirati children less than 12 years was 20.1% (95% CI 16.4-24.6%) in 2004.

Vitamin B12 decreases, but does not normalize, homocysteine and methylmalonic acid in end-stage renal disease: a link with glycine metabolism and possible explanation of hyperhomocysteinemia in end-stage renal disease.

The genetic and environmental factors influencing catabolism of homocysteine in end-stage renal disease (ESRD) patients remain poorly understood. This study investigated how genetic and nutritional influences affect the response to high-dose vitamin B(12) and folate treatment in ESRD patients with hyperhomocysteinemia. We studied 81 hemodialysis patients with hyperhomocysteinemia (> 16 micromol/L) on varied doses of a multivitamin containing 1 mg of folic acid per day. After screening blood work, all patients were switched to daily multivitamin therapy including 1 mg of folic acid for 4 weeks. Vitamin B(12), 1 mg/d, was added for an additional 4 weeks. Patients were then randomized to receive folic acid or placebo. The influence of the 3 methylenetetrahydrofolate reductase (MTHFR) 677 C-->T genotypes on the efficacy of vitamin therapy was assessed. In addition, we investigated how the metabolic complications of ESRD, including the relationship between methylmalonic acid (MMA) and circulating glycine, may contribute to hyperhomocysteinemia. There was no significant difference in total homocysteine (tHcy) levels between the MTHFR 677 C-->T genotypes during the screening phase of the trial. Treatment with a daily multivitamin containing 1 mg folate significantly lowered tHcy levels in all patients by 19.2%. Further supplementation with 1 mg vitamin B(12) resulted in greater tHcy reduction among subjects with the MTHFR 677 T/T genotype (P<.01, T/T v C/C or C/T) while lowering MMA equally in all MTHFR genotypes. There was a significant positive correlation between plasma glycine levels and MMA (P <.05). High-dose vitamin therapy significantly lowers, but does not normalize, MMA and tHcy levels. The MTHFR genotype, while influencing homocysteine levels, was not responsible for the majority of the elevation in plasma tHcy.

The severity of respiratory syncytial virus bronchiolitis in young infants in the United Arab Emirates.

Respiratory syncytial virus (RSV) respiratory infections are very common during infancy and account for the majority of hospitalizations during the fall and winter seasons. Patients vary in the severity of their illnesses, with most hospitalized patients needing oxygen and intravenous fluids. The objective of this study was to assess in hospitalized patients the severity of the disease in relation to age. We compared children who were <90 days old with children who were >90 days old for the duration of oxygen therapy, maximum oxygen concentration used, duration of stay and duration of intravenous fluids. We conducted a retrospective case review of national children <2 years admitted to the pediatric ward at Sheikh Khalifa Medical City with RSV proven bronchiolitis/pneumonia over a 3-month period from 1 September to 30 November 2001. Morbidity for group 1 (birth-90 days) and group 2 (91 days-2 years) was compared by the Mann-Whitney U-test using duration of oxygen therapy, maximum oxygen concentration used, duration of stay and duration of intravenous fluids. Multiple regression for duration of oxygen therapy was tested using the following risk factors as predictors: age group (1 or 2), previous ventilation, bronchopulmonary dysplasia (BPD) and prematurity. A total of 89 patients were admitted during this period. The mean age (SD) of group 1 (n = 28) and group 2 (n = 61) was 46.35 (25.57) days and 275.67 (156.79) days, respectively. The only statistically significant difference using the Mann-Whitney U-test was detected for duration of oxygen between the groups (p = 0.002). Using multiple regression, only age group acted as a predictor for duration of oxygen therapy (p < 0.001). This implies that the youngest children, group 1, are at a risk for prolonged oxygen therapy. Four patients from group 1 were admitted to the intensive care unit, of which two received ventilatory support. RSV respiratory infections affect infants <3 months old in a more severe form than older infants. Even though overall duration of stay was similar for both groups, young infants who in fact did require oxygen had a more protracted and severe illness compared with the older infants. This was evidenced by their longer duration of oxygen and more frequent need to be managed in the intensive care unit.

Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function.

The present study was designed to investigate the interaction between 5-methyltetrahydrofolate and tetrahydrobiopterin in modulating endothelial function. Tetrahydrobiopterin is a critical cofactor for nitric oxide synthase and maintains this enzyme as a nitric oxide- versus superoxide-producing enzyme. The structure of 5-methyltetrahydrofolate is similar to tetrahydrobiopterin and both agents have been shown to improve endothelium-dependent vasodilatation. We hypothesized that 5-methyltetrahydrofolate interacts with nitric oxide synthase in a fashion analogous, yet independent, of tetrahydrobiopterin to improve endothelial function. We demonstrate that 5-methyltetrahydrofolate binds the active site of nitric oxide synthase and mimics the orientation of tetrahydrobiopterin. Furthermore, 5-methyltetrahydrofolate attenuates superoxide production (induced by inhibition of tetrahydrobiopterin synthesis) and improves endothelial function in aortae isolated from tetrahydrobiopterin-deficient rats. We suggest that 5-methyltetrahydrofolate directly interacts with nitric oxide synthase to promote nitric oxide (vs. superoxide) production and improve endothelial function. 5-Methyltetrahydrofolate may represent an important strategy for intervention aimed at improving tetrahydrobiopterin bioavailability.

MAP kinases contribute to IL-8 secretion by intestinal epithelial cells via a posttranscriptional mechanism.

The intracellular pathways that regulate intestinal epithelial gene expression are poorly understood. In this study we examined the roles of extracellular signal-regulated kinase (ERK) and p38 in the expression of interleukin-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1) using the human intestinal cell line HT-29. HT-29 cells were treated with tumor necrosis factor-alpha (TNF-alpha) in the presence or absence of ERK and p38 pathway inhibitors. TNF-alpha treatment resulted in increased IL-8 and ICAM-1 protein and mRNA synthesis, increased ERK and p38 activity, and activation of the transcription factors activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB). Inhibition of the ERK and p38 pathways attenuated IL-8 secretion but did not alter ICAM-1 expression. Furthermore, AP-1 and NF-kappaB DNA binding was not affected by ERK and p38 inhibition. In contrast, ERK and p38 inhibition resulted in the accelerated degradation of the IL-8 mRNA, suggesting that in HT-29 cells, p38 and ERK contribute to TNF-alpha-stimulated IL-8 secretion by intestinal epithelial cells via a posttranscriptional mechanism that involves stabilization of the IL-8 transcript.

Arginine supplementation prevents necrotizing enterocolitis in the premature infant.

OBJECTIVES: To determine whether supplementation with L -arginine reduces the incidence of all stages of necrotizing enterocolitis (NEC) in premature infants with birth weight < or =1250 g and gestational age < or =32 weeks. STUDY DESIGN: In a randomized, double-blind, placebo-controlled study, 152 premature infants were prospectively, randomly assigned to receive either supplemental L -arginine (1.5 mmol/kg per day; n =75 [group A]) or placebo (control group; n = 77 [group B]) with oral feeds/parenteral nutrition during the first 28 days of life. Nutrient intake, plasma ammonia, arginine, and amino acid concentrations were measured in all infants at days 3, 14, and 28 and at the time of diagnosis of NEC. RESULTS: NEC developed in 5 infants in group A compared with 21 infants in group B (P <.001). Arginine intake and plasma arginine concentrations were similar in both groups at study entry and (as expected) increased in group A at days 14 and 28. Plasma arginine concentrations were lower in both groups at time of diagnosis of NEC. No significant differences in maternal and neonatal demographics, nutrient intake, plasma ammonia and total and essential amino acid concentrations were present between the two groups. CONCLUSIONS: Arginine supplementation (1.5 mmol/kg per day) in premature infants reduces the incidence of all stages of NEC.

The T-786-->C mutation in endothelial nitric oxide synthase is associated with hypertension.

Although the pathogenic mechanisms involved in predisposing individuals to hypertension are not well defined, evidence is accumulating that suggests a strong genetic transmission. Animal studies and some clinical investigations have revealed that aberrant NO production may be an important contributing factor. Indeed, a missense mutation in the endothelial NO gene caused by a Glu298Asp alteration has been strongly associated with essential hypertension, coronary artery spasm, and myocardial infarction. Recently, another point mutation caused by a T-786-->C transition in the 5'-flanking region of the endothelial NO synthase gene has been identified and, like the Glu298Asp mutation, is associated with coronary artery spasm. The present study was conducted to determine the effect of the T-786-->C point mutation on hypertension. We investigated the interaction between the endothelial NO synthase T-786-->C polymorphism and blood pressure in a large (n=705) clinically healthy population. Allele frequencies for the T and C alleles were 62% and 38%, translating into 39%, 46% and 15% of the population having the T/T, T/C, and C/C genotypes, respectively, for the T-786-->C point mutation. Subjects with the C/C genotype had significantly higher systolic blood pressures and were 2.16(95% confidence interval, 1.3 to 3.7) more likely to be hypertensive. Therefore, the -786 C/C genotype in NO synthase is a significant contributing factor for increasing the risk of essential hypertension.