Reduced total plasma homocyst(e)ine in children and adolescents with type 1 diabetes

OBJECTIVES: The objective was to investigate total plasma homocyst(e)ine (tHcy), methylenetetrahydrofolate reductase (MTHFR) genotype, and the contribution of diet to homocysteine values in children and adolescents with type 1 diabetes and a control group. STUDY DESIGN: A total of 78 children with type 1 diabetes and 59 members of an age- and sex-matched control group were recruited. Fasting samples were collected for tHcy, MTHFR genotype, serum vitamin B(12), serum folate, red cell folate, and plasma creatinine. Food frequency questionnaires targeted intake of folate, vitamin B(6), and vitamin B(12). RESULTS: Fasting tHcy was reduced in patients compared with the control group (4.7 vs 5.9 micromol/L, P <.001). Serum folate (P =.002), red cell folate(P <.001), and serum vitamin B(12) (P =.005) were higher, and plasma creatinine was lower. A significant difference in tHcy values between patients and the control group persisted after correction was done for these factors (r = 0.1, P =.02). No difference was seen in the frequency of MTHFR polymorphisms. tHcy was not elevated in those patients with the 677TT or 677T/1298C genotypes, although red cell folate was significantly higher in members of the case (P =.01) and control groups (P =.05) with a 677 TT genotype. Dietary intake of folate correlated with serum folate (r = 0.4,P =.005). CONCLUSION: tHcy values are lower in children and adolescents with type 1 diabetes. Higher serum levels of folic acid and vitamin B(12), reflecting differences in dietary intake between children with diabetes and members of a control group, partially account for this difference.     

窒息新生儿血清同型半胱氨酸与叶酸的变化

目的：探讨血清中高同型半胱氨酸（Hcy）血症及低叶酸水平与新生儿窒息的发生是否具有相关性,并对性别、胎龄等因素对血清中同型半胱氨酸及叶酸水平是否有一定影响进行分析。方法：应用酶联免疫吸附实验方法检测血清中Hcy水平,应用放射免疫法测定血中叶酸浓度。结果：①与无窒息对照组相比, 新生儿窒息患儿血清Hcy水平显著升高,而叶酸水平显著降低;②窒息组男婴血清Hcy、叶酸水平分别为15.82 ±2.51 μmol/L; 2.49 ±0.19 ng/mL,女婴为10.50±2.19 μmol/L; 2.38±0.40 ng/mL,男、女婴之间比较差异无显著性;③窒息组足月儿血清Hcy、叶酸水平为12.34 ±2. 01 μmol/L,2.58 ±0.19 ng/mL;早产儿为21.25±5.01 μmol/L; 2.14±0.34 ng/mL。早产儿Hcy水平显著高于足月儿（P<0.05）。结论：①新生儿窒息与血清Hcy及叶酸水平具有显著相关性。②血清Hcy及叶酸水平在性别上无显著差异。③缺氧窒息合并早产者血清Hcy水平升高最为显著。     

Homocysteine levels during fasting and after methionine loading in adolescents with diabetic retinopathy and nephropathy

OBJECTIVE: To assess plasma homocysteine levels in adolescents and young adults with type 1 (insulin-dependent) diabetes with and without microvascular complications. STUDY DESIGN: Homocysteine levels were measured during fasting and after methionine loading in plasma of 61 patients with onset of diabetes before the age of 12 years and duration of disease longer than 7 years. They had an albumin excretion rate (AER) between 20 and 200 microg/min in 2 of 3 overnight urine collections in a period of 6 months and/or retinopathy. Patients with persistent microalbuminuria were divided into 2 groups: subjects with AER of 20 to 70 microg/min and patients with AER of 70 to 200 microg/min. Adolescents (n = 54) without signs of diabetic retinopathy or nephropathy and matched control subjects (n = 63) were also studied. RESULTS: Homocysteine concentrations before and after methionine load were higher in adolescents with diabetic complications than in healthy subjects (fasting values: 12. 4 +/- 7.9 micromol/L vs 7.8 +/- 4.2 micromol/L; P <.01; after methionine load: 28.1 +/- 13.2 micromol/L vs 16.6 +/- 7.3 micromol/L; P <.005). Values of 11.9 micromol/L or higher were considered to constitute fasting hyperhomocysteinemia. The increase of homocysteine concentrations was particularly evident in young diabetic patients with AER >70 microg/min (fasting values: 14.7 +/- 5.6 micromol/L; after methionine load: 34.2 +/- 12.6 micromol/L) and in patients with proliferative retinopathy (fasting values: 15.1 +/- 5.0 micromol/L; after methionine load: 36.8 +/- 12.5 micromol/L). CONCLUSIONS: Increased plasma homocysteine concentrations may contribute to increased morbidity and death from cardiovascular disease in adolescents and young adults with diabetic retinopathy and nephropathy.     

Folic acid improves endothelial function in children and adolescents with type 1 diabetes

OBJECTIVE: To evaluate the effect of folate supplementation on endothelial function in children and adolescents with type 1 diabetes. STUDY DESIGN: Thirty-six subjects with type 1 diabetes age 13.6+/-2.6 years completed a randomized, double-blind, placebo-controlled crossover trial. Each subject received 8 weeks of oral folic acid (5 mg/d) and 8 weeks of placebo, with an 8-week washout period. Before and after each intervention, we assessed endothelial function by using brachial artery responses to flow (flow-mediated dilatation [FMD]) and glyceryl trinitrate, von Willebrand factor, glucose, hemoglobin A1c, total plasma homocyst(e)ine (tHcy), vitamin B(12), serum folate, and red cell folate (RCF). RESULTS: Folic acid increased FMD by 2.58 (3.1-5.7) % (95% confidence interval, 1.28-3.88), whereas placebo did not change FMD (-0.42%; 95% confidence interval, -1.67 to 0.83; P<.001). Folic acid increased serum folate by 14 nmol/L (6.2 ng/mL, P<.001) and RCF by 467.2 nmol/L (206 ng/mL, P<.001). Change in FMD was related to change in serum folate (r=0.46, P=.005) and RCF (r=0.39, P=.02). Glyceryl trinitrate responses, von Willebrand factor, tHcy, and hemoglobin A1c were not affected by the intervention. CONCLUSIONS: Short-term high-dose folic acid improves endothelial function in children and adolescents with type 1 diabetes and normal folate status independently of tHcy.     

Plasma homocysteine levels and folate status in children with sickle cell anemia.

PURPOSE: A sensitive inverse relationship between plasma homocysteine concentration and folate status has been demonstrated. Although children with sickle cell anemia (SCA) are at potential risk for folate deficiency, plasma homocysteine levels have not been reported in such patients. Therefore, a study was designed to assess plasma homocysteine levels as a marker of folate status. DESIGN: Plasma homocysteine concentrations were measured in 120 children with SCA (102 in steady state and 18 during an acute complication) who had never received supplemental folic acid. Folate status was directly assessed in 34 of these patients. RESULTS: Plasma homocysteine levels in the patients with SCA and control subjects were similar. The mean value +/- 1 SD was 5.8+/-2.5 micromol/L (range, 1.6 to 14.1 micromol/L) in the patients with SCA and 6.1+/-2.7 micromol/L (range, 1.7 to 15.3 micromol/L) in 73 pediatric control subjects. In a subpopulation of the study group (34 children), simultaneous serum folate, red cell folate, and total homocysteine concentrations were also measured. Their serum folate and red cell folate concentrations were normal: 12.4+/-10.0 nmol/L (range, 1 to 42 nmol/L) and 604+/-374.7 nmol/L (range, 205 to 1741 nmol/L), respectively. There was no correlation of plasma homocysteine concentration with various clinical or laboratory measures or with red cell folate concentration. CONCLUSION: Folate stores in children with SCA not receiving folic acid supplements are adequate despite an underlying hemolytic anemia.     

Serum total homocysteine concentrations in children and adolescents in Jos, Nigeria

BACKGROUND: Although the elevation of circulating total serum homocysteine (tHcy) concentration in a fasting state is associated with an increased risk of occlusive vascular disease in adults, the levels in children in Nigeria are not known. AIM: The goals of this study were to describe the distribution of tHcy among a representative sample of children and adolescents in Jos, Nigeria, and to test for differences in tHcy among sex and age categories. METHODS: The sampling scheme, which included persons aged 10 to 19 years, was a stratified, multistage probability design. This cross sectional study involved 182 school children drawn from secondary schools in Jos, Nigeria between January and July 2003. Fasting venous samples were collected and assayed for tHcy, Total protein and Albumin. Anthropometric measurements were taken. RESULT: The mean tHcy concentrations were 2.7 +/- 2.4 (95% CI 2.4-2.9), 3.5 +/- 3.2 (3.3-3.8) and 3.6 +/- 3.2 (3.3-4.1), 4.1 +/- 3.6 (4.0-4.4) micromol/l for the girls and boys aged 10-14 and 15-19 years, respectively. Albumin levels correlate positively with plasma total homocysteine, tHcy (r = 0.45, P = 0.03). CONCLUSION: This study provided age-specific data regarding tHcy concentrations between 10-19 years population in Jos, Nigeria. The tHcy concentration increased as a function of age in both sexes.     

Improved folate status in children and adolescents during voluntary fortification of food with folate

OBJECTIVE: To assess longitudinal changes in folate status in South Australian children and adolescents during fortification of food with folic acid. METHODS: Sixty-nine children and adolescents (age 12.8 +/- 2.3 years), 47 with diabetes and 22 healthy controls, had their folate status assessed at the beginning of 1999 and again after a mean 1.1 +/- 0.23 years. Intake of folate at baseline was assessed with a quantitative food frequency questionnaire. RESULTS: Baseline red cell folate (mean +/- standard deviation (SD)) was 756 +/- 294.5 nmol/L and remained constant at follow up at 736 +/- 299 nmol/L (P = 0.55) in the whole group. Serum folate increased from 24.4 +/- 6.3 nmol/L to 27.2 +/- 8.8 nmol/L (P = 0.002). Children with diabetes showed a significant increase in serum folate (from 26.3 +/- 5.7-30.1 +/- 7.9, P < 0.001) and stable red cell folate (835.8 +/- 278.6 and 808.6 +/- 296.7, P = 0.51) between baseline and the second samples, while controls showed stable serum (20.4 +/- 5.7 and 21.1 +/- 7.7, P = 0.7) and red cell folate (586.6 +/- 255.9 and 579.8 +/- 240.1, P = 0.92). A third sample collected in 17 subjects after a further 9 +/- 1.3 months showed a further increase in serum and red cell folate. Mean folate intake at baseline was 301 +/- 129 micro g/day, below the mean recommended for prevention of neural tube defects. CONCLUSIONS: Voluntary fortification of food with folate is associated with improved folate status in South Australian children and adolescents, but may not be sufficient at current levels to provide maximal protection against neural tube defects at a population level.     

Homocysteine, MTHFR C677 T, vitamin B12, and folate levels in Thai children with ischemic stroke: a case-control study

Hyperhomocysteinemia has been identified as a risk factor for venous and arterial thrombosis especially in adult populations. Twenty-eight patients with an initial diagnosis of ischemic stroke and 100 controls, aged 相似文献   

Plasma total homocysteine increases from day 20 to 40 in breastfed but not formula-fed low-birthweight infants

Homocysteine is an intermediate in the folate cycle and methionine metabolism. This study investigated whether formula-fed infants have different plasma total homocysteine to their breastfed counterparts, and during what period any difference developed. Plasma total homocysteine was determined in 53 formula-fed and 15 breastfed healthy low-birthweight babies (< or = 2500 g) around days 10, 20 and 40. Total homocysteine was also measured in human milk. Mean +/- SD plasma total homocysteine levels (micromol l(-1)) at days 10, 20 and 40 were 6.4 +/- 2.6, 6.7 +/- 2.4 and 9.1 +/- 2.4 (breastfed), and 7.5 +/- 3.2, 7.3 +/- 2.1 and 7.4 +/- 1.6 (formula-fed). Homocysteine of breastfed babies at day 40 was higher than that of breastfed babies at day 20 (p < 0.0001), and that of formula-fed counterparts at day 40 (p = 0.002). Homocysteine correlated negatively with formula (day 10) and breast milk (day 40) volume intakes. Median (range) homocysteine in 12 mature human milk samples was 0.30 (not detectable to 0.7) micromol l(-1). Conclusion: Increasing plasma total homocysteine in breastfed babies to higher levels compared with formula-fed babies may be caused by a gradually developing suboptimal B-vitamin status in lactating women.     

Serum interleukin-18 levels are raised in diabetic ketoacidosis in Chinese children with type 1 diabetes mellitus

OBJECTIVE: To investigate the role of serum interleukin (IL-18) in children with type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis (DKA). DESIGN: Case-control study. SUBJECTS: Sixty-one children with T1DM including 28 with DKA and 33 without DKA and 30 age - and sex-matched healthy controls were recruited. METHODS: Serum IL-18, IL-12, and IFN-gamma levels were measured in all subjects by enzyme linked immunosorbent assay. RESULTS: Serum IL-18 levels were significantly higher in patients with DKA than those in patients without DKA (759.2 +/- 353.8 pg/mL vs. 634.9 +/- 399.7 pg/mL, P = 0.001) and healthy controls (310.0 +/- 265.3 pg/mL). The serum IL-12 and IFN-gamma levels were not different between patients and controls (277.5 +/- 207 pg/mL vs. 351.4 +/- 223.4 pg/mL, P = 0.45 and 7.02 +/- 7.53 pg/mL vs. 5.59 +/- 5.34 pg/mL, P = 0.21, respectively). CONCLUSION: Serum IL-18 levels are increased in children with type 1 diabetes mellitus and could be a predictor of diabetic ketoacidosis.     

Elevation of serum stem-cell factor in postoperative biliary atresia

BACKGROUND: Biliary atresia (BA) is one of the most common causes of neonatal cholestasis. Stem-cell factor (SCF) has been implicated in the development of fibrosis in various diseases. The objective of the present study was to examine the significant role of SCF in BA. METHODS: Fifty-seven pediatric patients with BA after Kasai operation and 30 healthy children were recruited. The mean ages of BA patients and controls were 6.1 +/- 0.6 years and 6.1 +/- 0.7 years, respectively. The patients were categorized into two groups according to their serum levels of total bilirubin (TBil < 2 mg/dL, no jaundice vs TBil > or = 2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT < 100 vs ALT > or = 100 U/L). The serum SCF levels were determined on commercially available enzyme-linked immunosorbent assay. RESULTS: The mean serum SCF level of the BA children was higher than that of normal controls (748.3 +/- 17.9 pg/mL vs 582.2 +/- 17.3 pg/mL; P < 0.001). Subsequent analysis demonstrated that the BA patients with serum ALT > or = 100 U/L had significantly greater levels of serum SCF compared to those with serum ALT < 100 U/L (796.5 +/- 22.6 pg/mL vs 694.7 +/- 25.0 pg/mL, respectively; P = 0.002). In addition, serum SCF levels were significantly elevated in the patients with portal hypertension (PH) compared with those without PH (810.0 +/- 18.8 pg/mL vs 634.1 +/- 20.1 pg/mL, P < 0.001). CONCLUSION: The current study showed that BA patients had higher serum SCF levels compared with controls. The significant elevation in SCF levels is associated with the presence of PH and the degree of hepatic injury. These findings suggest that SCF may play a part in the pathogenesis of hepatic fibrosis in BA patients after Kasai procedure.     

过敏性紫癜病儿树突细胞分泌白细胞介素-12水平与T_H1/T_H2的变化

目的：观察过敏性紫癜(HSP)病儿外周血树突细胞(DC)产生IL12的变化,并探讨其对TH1/TH2平衡的影响及在HSP发病机制中的意义。方法：应用酶联免疫吸附试验(ELISA)检测60例HSP病儿(HSP组)及21例健康儿童(对照组)血浆干扰素γ(IFNγ)、白细胞介素4(IL4)、白细胞介素12(IL12)水平。并对其中22例HSP病儿及21例健康儿童外周血单个核细胞(PBMC)进行体外培养以诱生出DC,用ELISA法检测培养上清液中IL12水平,同时应用间接免疫荧光法检测CD1a+细胞表达率。结果：①HSP组血浆IFNγ水平低于对照组(30.59±11.27pg/mLvs43.38±19.19pg/mL,P<0.01),IL4水平高于对照组(45.08±9.19pg/mLvs32.95±7.10pg/mL,P<0.01),IFNγ/IL4比值低于对照组(0.70±0.28vs1.33±0.57,P<0.01),IL12水平低于对照组(153.95±91.88pg/mLvs323.06±162.34pg/mL,P<0.01);HSP组和对照组各自血浆中IL12水平与IFNγ水平呈正相关(P<0.01,0.05),与IL4水平无相关性(P>0.05),与IFNγ/IL4比值呈正相关(P<0.01)。②HSP组培养上清液IL12水平低于对照组(357.06±153.56pg/mLvs489.80±213.45pg/mL,P<0.05),且与血浆IL12水平呈正相关(P<0.01)。③HSP组CD1a+细胞表达率低于对照组(27.42±10.75)%vs(35.68±12.18)%,(P<0.05),与培养上清液和血浆IL12水平皆呈正相关(P<0.01)。结论：HSP病儿存在TH1/TH2平衡失调,TH1功能的下降与血浆IL12水平低下呈正相关,而后者又与DC数量减少和/或功能低下关系密切,表明HSP病儿外周血DC数量减少和/或功能低下间接导致了TH1/TH2平衡的失调。     

Possible effect of leptin on renal magnesium excretion in adolescent patients with type 1 diabetes

BACKGROUND: Hypomagnesaemia and hyperleptinemia are common in patients with diabetes. Moreover, it has been demonstrated that leptin stimulates diuresis and natriuresis. The aim of this study was to evaluate the relationship between serum leptin, serum magnesium (Mg) and urinary Mg/urinary creatinine levels in patients with type 1 diabetes. METHODS: Serum leptin and Mg and urinary Mg/urinary creatinine levels were measured in 67 patients with diabetes (33 girls and 34 boys). The age, diabetes duration, anthropometric and metabolic parameters of the subjects were matched between girls and boys. The relation of serum leptin levels to serum and urinary Mg/urinary creatinine levels was assessed. RESULTS: Serum leptin levels of girls with diabetes were higher than those of the boys (14 +/- 5.3 microg/L vs 5.8 +/- 1.5 microg/L, P < 0.001, respectively). The differences for serum Mg and for urinary Mg/urinary creatinine levels were not significant between girls and boys with diabetes. Leptin levels were correlated with urinary Mg/urinary creatinine levels in both girls and boys (r = 0.39, P = 0.02 and r = 0.37, P = 0.03, respectively). In a multivariate regression model, leptin emerged as independent correlates for mean urinary Mg/urinary creatinine in both girls and boys with the total variance explained being 14%, and 15%, respectively. CONCLUSION: The data suggest that serum leptin might be related to increased urinary Mg loss in patients with type I diabetes.     

肾病综合征患儿血清铁与转铁蛋白的变化

目的：肾病综合征(NS)患儿尿中丢失白蛋白的同时也伴有转铁蛋白的丢失,测定血清铁及转铁蛋白等铁代谢相关指标以及尿转铁蛋白,了解其变化及其相互关系。方法：NS患儿37例,测定其治疗前和恢复期铁代谢相关指标(血清铁、铁蛋白、转铁蛋白、转铁蛋白饱和度、总铁结合力以及外周血红细胞参数)及尿转铁蛋白,并与正常对照组比较。结果：①在NS治疗前血清铁为18.8±3.8μmol/L,分别与恢复期的21.0±3.5μmol/L,及对照组的22.2±3.8μmol/L比较,差异有显著性(P<0.01);转铁蛋白为1.9±0.3g/L,分别与恢复期的2.9±0.6g/L和对照组的3.1±0.5g/L比较,差异有显著性(P<0.01);总铁结合力为56.4±9.2μmol/L,分别与恢复期的51.9±7.7μmol/L和对照组的50.7±6.8μmol/L比较,差异亦有显著性(均P<0.01);转铁蛋白饱和度为(55.7±9.2)%,与NS恢复期及对照组的(47.4±13.3)%,(46.4±8.2)%比较,差异有显著性(P<0.01)。②血清白蛋白与转铁蛋白呈正相关(r=0.609,P<0.01)。③血清转铁蛋白浓度与尿转铁蛋白呈负相关(r=-0.550,P<0.01)。结论：NS患儿血清铁及转铁蛋白明显降低,可能与转铁蛋白从尿中丢失有关。     

Alanine amino transferase concentrations are linked to folate intakes and methylenetetrahydrofolate reductase polymorphism in obese adolescent girls

OBJECTIVE: The objective of this study was to investigate the consequences of low dietary folate intake and the impact of the 677 C-->T methylenetetrahydrofolate reductase (MTHFR) common mutation on liver function in obese adolescents. METHODS: Fifty-seven obese girls (BMI = 36.1 +/- 6.0 kg/m) aged 14.1 +/- 1.5 years were included before starting a weight reduction program. Dietary intakes for folate were assessed by means of an adapted food frequency questionnaire (n = 50). Liver enzymes, plasma lipids, glucose metabolism parameters, ferritin, homocysteine and erythrocyte folate content were measured in plasma or blood obtained under fasting conditions. The MTHFR 677 C-->T polymorphism, which is associated with decreased enzyme activity, was determined using PCR. Body composition was assessed using dual x-ray absorptiometry. RESULTS: Twenty-three subjects were heterozygote (CT) for the mutation and 5 were homozygote (TT). An increase in alanine amino transferase (ALT) and ALT/aspartate aminotransferase ratio was associated with the mutation (F = 4.46, P = 0.016 and F = 5.92, P = 0.0049, respectively). Alanine amino transferase was correlated negatively to folate intake (r = -0.32, P = 0.024) (n = 50) and positively to homocysteine concentrations (r = 0.30, P = 0.025). Body composition was similar among the 3 genotypic groups. Ferritin was also correlated to ALT concentrations of the entire group (P = 0.009). CONCLUSION: Our data suggest that folate intake and the MTHFR polymorphism represent a part of the link between antioxidant status and liver disease in obese adolescent girls.     

Plasma endothelin-1 concentrations in children with cirrhosis and their relationship to renal function and the severity of portal hypertension

BACKGROUND: Plasma endothelin-1 (ET-1) is a potent vasoconstrictor peptide involved in the pathogenesis of several disorders. Endothelin-1 concentrations are increased in adult patients with cirrhosis. However, little is known about ET-1 concentrations in children with cirrhosis. METHODS: Radioimmune assay was used to measure plasma ET-1 concentrations in 19 children with cirrhosis (8 patients with ascites, and 11 without ascites), and 11 age- and sex-matched healthy children. The plasma ET-1 concentrations were correlated with the mean blood pressure, creatinine clearance, and severity of portal hypertension, as measured by portal flow volume and portal flow velocity. RESULTS: Patients with cirrhosis and ascites had increased plasma ET-1 concentrations compared with patients who did not have ascites (6.8 pg/mL +/- 0.62 pg/mL vs. 4.6 pg/mL +/- 0.35 pg/mL; mean +/- SEM; < 0.01) and controls (3.6 pg/mL +/- 0.27 pg/mL; mean +/- SEM; < 0.0005). Plasma ET-1 concentrations were higher in patients with cirrhosis who did not have ascites compared with controls ( < 0.005). No significant differences were observed between concentrations of the patients with cholestasis and those without cholestasis (5.4 pg/mL +/- 0.52 pg/mL vs. 5.2 +/- 0.32 pg/mL; mean +/- SEM; = 0.1). Plasma ET-1 concentrations correlated positively with the mean blood pressure ( = 0.58; < 0.05) and negatively with renal function, as measured by creatinine clearance ( = -0.7; <0.005). However, no correlation was detected between ET-1 concentrations and portal flow volume ( = -0.02; = 0.4) or portal flow velocity ( = -0.16; = 0.4). CONCLUSIONS: Plasma ET-1 concentrations are increased in children with cirrhosis, with or without ascites, compared with controls. Patients with cirrhosis and ascites have increased ET-1 concentrations compared with those without ascites. The degree of increase does not relate to the severity of portal hypertension. This increase tends to maintain systemic blood pressure but is associated with a decrease in renal function.     

Correlation of serum parathormone level with biochemical parameters in chronic renal failure

A prospective study was carried out to assay the level of serum intact parathormone and its correlation with biochemical parameters in patients with chronic renal failure (CRF). The study included 64 children (44 with CRF, and 20 age and sex matched controls). Serum intact parathormone (iPTH), serum creatinine, urea, calcium, inorganic phosphate and alkaline phosphatase were estimated. Creatinine clearance (Ccr) was estimated by Schwartz formula. Patients with CRF were divided into four groups based on their Ccr (mild CRF with mean Ccr 59.17 +/- 1:18.53 mL/min/1.73 m2 (n = 6) moderate CRF with mean Ccr 34.98 +/- 7.75 mL/min/1.73 m2 (n = 7); severe CRF with mean Ccr 17.71 +/- 5.40 mL/min/1.73 m2 (n = 15); and end-stage renal disease with mean Ccr 6.46 +/- 1.71 mL/min/1.73 m2 (n = 16). Mean serum iPTH levels were 93.00 +/- 46.62 pg/mL in CRF and 16.52 +/- 9.35 pg/mL in controls. Groupwise mean serum (iPTH) levels were 48.50 +/- 4.76, 67.29 +/- 7.91, 82.42 +/- 9.67 and 130.66 +/- 58.74 pg/mL in mild, moderate, severe CRF and endstage renal failure respectively. Mean serum iPTH level of CRF (93.00 +/- 46.42 pg/mL) negatively correlated with mean Ccr (22.02 +/- 18.53 mL/min/l.73 m2) (P < 0.001) and mean serum calcium (7.30 +/- 1.02 mg/dL) (P < 0.001) and positively correlated with mean inorganic phosphate (5.76 +/- 1.1 mg/dL) (P < 0.05) and mean alkaline phosphatase (355.14 +/- 185.53 UL) (P < 0.001). We conclude that increased iPTH level occur even early in the course of CRF and progressive hypocalcemia and hyperphosphatemia are the initiating factors for the development of hyperparathyroidism.     

Energy expenditure, inflammation, and oxidative stress in steady-state adolescents with sickle cell anemia

Sickle cell anemia (HbSS) is characterized by hypermetabolism, chronic inflammation, and increased oxidative stress, but the relationship between these factors is undefined. In this study, we examined indicators of inflammatory process and markers of oxidative damage and their impact on resting energy expenditure (REE) in stable HbSS adolescents (n = 35) and healthy controls carrying normal hemoglobin genotype (HbAA) (n = 39). C-reactive protein (CRP), white blood cell (WBC) count, and proinflammatory cytokines were measured as markers of inflammation and 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-IsoPM) as a marker of oxidative stress. REE was measured by indirect calorimetry. WBC counts (11.90 +/- 5.3 x10/muL versus 5.6 +/- 1.9 x10/muL; p < 0.001), serum CRP (9.1 +/- 11.0 mug/mL versus 0.4 +/- 0.7 mug/mL; p < 0.001) and serum IL-8 (7.5 +/- 4.4 pg/mL versus 5.5 +/- 4.8 pg/mL; p = 0.011) were higher in HbSS than HbAA, suggesting an anti-inflammatory response in HbSS. Higher urinary F2-IsoPM in HbSS (1.2 +/- 0.4 versus 0.7 +/- 0.3 ng/mg creatinine; p < 0.001) indicates increased oxidative stress. Fat free mass (FFM), hemoglobin (Hgb), interleukin (IL)-8, and F2-IsoPM were independent predictors of REE in HbSS (overall r = 0.778; p < 0.001). Low-grade inflammation and increased oxidative stress are present in adolescents with HbSS in the absence of acute crisis, and their markers are correlated with elevated REE.     

Plasma zinc and growth status in preadolescent children with cystic fibrosis

OBJECTIVE: To investigate plasma zinc status in relation to dietary and supplemental zinc intake, growth and pulmonary status in preadolescent children with cystic fibrosis (CF) and pancreatic insufficiency (PI). METHODS: Fasting plasma zinc was assessed in children (age, 8-11 years) with CF and PI. Food (7-day weighed records) and supplemental zinc intake, serum alkaline phosphatase and albumin, pulmonary function (spirometry), coefficient of fat absorption (%COA, 72-hour fecal fat) and growth status [height adjusted for genetic potential (AHAZ), weight (WAZ) and BMI Z scores (BMIZ)] were assessed. RESULTS: For the 62 children (32 males), mean plasma zinc (+/-SD) was 16.8 +/- 3.1 micromol/L (110 +/- 20 ug/dL). Sixty-five percent of the subjects had levels above the study reference range of 9.2 to 15.3 micromol/L (60-100 ug/dL); no subjects had low zinc levels. Median (range) total daily zinc intake was 279% (83-988%) recommended dietary allowance, growth status was suboptimal (mean +/- SD: AHAZ, -0.8 +/- 1.0; WAZ, -0.5 +/- 1.2; BMIZ, -0.2 +/- 1.1), and forced expiratory volume at 1 second (FEV1) was 92 +/- 13% predicted. Plasma zinc was not correlated with growth, pulmonary or alkaline phosphatase status. Plasma zinc was correlated with serum albumin (r = 0.25, P < 0.05) and was inversely correlated with coefficient of fat absorption (as %; r = -0.30, P = 0.02). CONCLUSIONS: Under current patterns of care in CF Centers, total zinc intake and plasma zinc status were adequate. These findings suggest that zinc was not a limiting micronutrient for preadolescent children with CF and PI and mild-to-moderate lung disease, and not likely contributing to their suboptimal growth status.     

Ghrelin levels in young children with Prader-Willi syndrome

OBJECTIVE: To explore the hypothesis that high ghrelin levels contribute to obesity in Prader-Willi syndrome (PWS), we assessed whether the increased levels observed in older persons with PWS exist in very young children, before the onset of hyperphagia. STUDY DESIGN: We measured ghrelin levels in nine children with PWS (17-60 months of age) and eight healthy control subjects of equivalent body mass index (BMI), age, and sex. RESULTS: PWS and control groups had equivalent BMI (16.8 +/- 1.4 vs 16.1 +/- 0.9 kg/m(2), respectively; P = .24), age (37.8 +/- 15.4 vs 50.3 +/- 17.7 months; P = .14), and sex. PWS and control groups also had equivalent fasting levels of total ghrelin (787 +/- 242 vs 716 +/- 135 pg/mL, respectively; P = .24), bioactive ghrelin (102 +/- 35 vs 91 +/- 23 pg/mL; P = .45), insulin, and glucose. Ghrelin correlated negatively with BMI among controls (r = -0.760, P = .029) but not PWS (r = 0.015, P = .97). CONCLUSIONS: Children <5 years of age with PWS, who had not yet developed hyperphagia or excessive obesity, had normal ghrelin levels, in contrast with the hyperghrelinemia of older, hyperphagic people with PWS. It is possible that ghrelin levels increase suddenly before hyperphagia develops.