Low vitamin D status in children with sickle cell disease

OBJECTIVES: To examine vitamin D status in children with sickle cell disease (SCD)-SS and its relation to season and dietary intake. STUDY DESIGN: Growth, dietary intake, 25-hydroxyvitamin D (25-OHD), and parathyroid hormone levels were measured. Children with low and normal vitamin D status were compared. Low vitamin D status was defined as a serum concentration of 25-OHD <27.5 nmol/L. Serum 25-OHD and parathyroid hormone levels were compared among children with SCD-SS and healthy children. RESULTS: Children with SCD-SS (n=65), 5 to 18 years of age, were evaluated. Mean (+/-SD) serum 25-OHD concentration was 25.5 +/- 12.8 nmol/L; 65% of subjects had low vitamin D status. Low vitamin D prevalence was highest during spring (100%). Children with SCD-SS were at higher risk for low vitamin D status than healthy children. Vitamin D intake was lower in subjects with SCD-SS and low vitamin D than those with normal serum vitamin D status (P <.05). CONCLUSIONS: Low serum vitamin D status was highly prevalent in black children with SCD-SS. Vitamin D status was associated with season and dietary intake.     

Deficiency of vitamins E and A in cystic fibrosis is independent of pancreatic function and current enzyme and vitamin supplementation

Abstract The aim of this study was to evaluate to what extent serum vitamins A and E in cystic fibrosis are affected by the underlying disease, pancreatic sufficiency or insufficiency, meconium ileus, nutritional status, age and treatment (enzyme and vitamin supplementation). Serum vitamin A and E levels were determined by high performance liquid chromatography in 210 cystic fibrosis patients, subdivided according to clinical condition into four subgroups (unsupplemented pancreatic insufficiency, supplemented meconium ileus, pancreatic sufficiency, supplemented pancreatic insufficiency) and compared with 42 control subjects. Vitamin A and E levels were generally lower in cystic fibrosis patients than in controls (P<0.002 andP<0.001 respectively). Subjects with pancreatic insufficiency regularly receiving enzyme and vitamin supplementation had significantly lower vitamin A (P<0.05) and vitamin E (P<0.01) levels than controls. In subjects with pancreatic sufficiency only vitamin A was significantly lower than in controls (P<0.01). Vitamin levels were not age-dependent in cystic fibrosis, and no significant correlation with standardized body weight (Z-score) was observed.Conclusion Cystic fibrosis patients show a clear tendency to vitamin A and E deficiency, irrespective of pancreatic function, body weight and standardized supplementation with pancreatic extract and liposoluble vitamins. Since the clinical significance of this deficiency is still not clear, longitudinal studies of cystic fibrosis patients with and without adequate vitamin supplementation are required.     

儿童急性淋巴细胞性白血病细胞内IL-6IFN-γ水平变化及其临床意义

目的：了解急性淋巴细胞性白血病(acutelymphoblasticleukemia,ALL)在不同病期单个核细胞内白细胞介素-6(interleukin-6,IL-6)、γ-干扰素(interferon-γ,IFN-γ)水平变化规律,并探讨不同病期ALL患儿IL-6与IFN-γ之间相关关系,以期为临床开展细胞因子等细胞生物学方法治疗白血病提供一定依据。方法：采用流式细胞仪活细胞直接/间接免疫荧光法测定42例ALL患者初发期及缓解期静脉血经培养和刺激后单个核细胞内IL-6及IFN-γ的表达水平。20例健康儿童作为正常对照。结果：①ALL患儿初发期其静脉血单个核细胞内IL-6表达水平为81.74±9.31,较正常对照组的5.67±0.96明显升高(P<0.01),而静脉血单个核细胞内IFN-γ表达水平为1.31±0.32,较正常对照组的1.46±0.49有所下降(P<0.01);经化疗获得缓解后,ALL患者静脉血单个核细胞内IL-6表达水平为27.52±3.40,较初发期明显降低(P<0.01),却仍较正常对照组升高(P<0.01),而静脉血单个核细胞内IFN-γ表达水平为1.97±0.72,较初发期明显升高(P<0.01),且较正常对照组也明显升高,(P<0.01)。②ALL患儿不同病期静脉血单个核细胞内IL-6与IFN-γ表达呈明显的负相关(r=-0.476,P<0.05)。结论：ALL患儿静脉血单个核细胞内IL-6水平与其病情是否缓解有着密切的关系,ALL治疗中单个核细胞内IL-6水平下降表示ALL可能获得缓解。当ALL患者经化疗获得缓解时,IFN-γ的水平增高,但二者相互作用机制及其与ALL患者所处病期的因果关系还有待进一步阐明。     

Prevalence of vitamin K deficiency in children with mild to moderate chronic liver disease

OBJECTIVES: Children with chronic liver disease are at risk for vitamin K deficiency because of fat malabsorption and inadequate dietary intake. The objective of this study was to determine the prevalence of vitamin K deficiency in children with mild to moderate chronic cholestatic and noncholestatic liver disease. METHODS: Vitamin K status was examined in 43 children (0.25-15.9 years) with mild to moderate chronic cholestatic liver disease, 29 children (0.9-16.9 years) with chronic mild to moderate noncholestatic liver disease, and in 44 healthy children (1-18 years). Vitamin K status was assessed by the plasma PIVKA-II (protein induced in vitamin K absence) assay (enzyme-linked immunosorbent assay). Plasma PIVKA-II values greater than 3 ng/mL are indicative of vitamin K deficiency. RESULTS: The mean plasma PIVKA-II (+/-SD) in cholestatic, noncholestatic, and healthy children was 61.9 +/-144, 1.2 +/- 3, and 2.1 +/- ng/mL, respectively (P < 0.002). Fifty-four percent of the children supplemented with vitamin K had plasma PIVKA-II greater than 3 ng/mL. Plasma conjugated bilirubin, total bile acids, and severity of liver disease were positively correlated with plasma PIVKA-II levels (P < 0.05). CONCLUSIONS: Vitamin K deficiency is prevalent in children with mild to moderate chronic cholestatic liver disease, even with vitamin K supplementation. Elevated PIVKA-II levels occurred in children with a normal prothrombin, indicating that more sensitive markers of vitamin K status should be used in children with chronic liver disease. Vitamin K deficiency was related to degree of cholestasis and severity of liver disease in children. Children without cholestasis did not exhibit vitamin K deficiency.     

Subclinical Vascular Endothelial Dysfunctions and Myocardial Changes With Type 1 Diabetes Mellitus in Children and Adolescents

Vascular endothelial dysfunction, accelerated thickening of arterial intima, and changes in ventricular functions contribute to increased cardiovascular morbidity in type 1 diabetes mellitus (T1DM). This study aimed to investigate the functional-structural changes in the arteries and myocardium together with affection of highly sensitive C-reactive protein (hsCRP), circulating endothelial cells (CECs), and vitamin C levels in children with T1DM. Also, to test the association with early atherosclerotic changes. The study included 30 children with a diagnosis of T1DM and 30 healthy subjects matched by sex, age, and body mass index. Serum lipids, HbA1c, hsCRP, vitamin C, and CECs were detected. Corrected QT interval (QTc), cardiac dimensions, and left ventricular (LV) functions were assessed using conventional echocardiography. Noninvasive ultrasound was used to measure brachial artery flow-mediated dilation (FMD) responses and carotid intima-media thickness (IMT). The QTc interval was significantly higher in the diabetic patients than in the control subjects (P < 0.001). The findings showed LV diastolic dysfunction as reflected by significantly lower early peak flow velocity, decreased E/A ratio, increased early filling deceleration time (DcT), and prolonged isovolumic relaxation time (IVRT) (P < 0.001 for each). The children with diabetes had a significantly lower FMD response, increased IMT, lower vitamin C level, higher hsCRP, and higher CEC compared with the control subjects (P < 0.001 for each). A positive correlation between CEC and HbA1c was found (P = 0.004). An alteration in myocardial function and endothelial dysfunction may begin early with the association of early atherosclerotic changes. These changes are accelerated when glycemic control is poor. The authors recommend early and close observation of children with diabetes for any alterations in cardiac and vascular endothelial function. Vitamin C supplementation may reduce the risk of complications.     

Plasma and erythrocyte vitamin E levels in children with insulin dependent diabetes mellitus.

Vitamin E is considered to be one of the most important antioxidants. There is a trend today to supply diabetic children with vitamin E in order to prevent microvascular complications. In this study, our objective was to demonstrate validity of plasma and erythrocyte vitamin E levels in diabetic children. This study was conducted on twenty-five diabetic patients aged from 7-16 years and ten non-diabetic, age-matched healthy subjects as the control group. Vitamin E levels were measured by high-performance liquid chromatography. There was no significant difference between the mean plasma vitamin E levels of diabetic and control groups, 870.80 +/- 220.51 micrograms/dl and 891 +/- 221.21 micrograms/dl, respectively (p > 0.05). The mean erythrocyte vitamin E levels of diabetic and control groups were significantly different: 183.12 +/- 62.58 micrograms/dl and 246.90 +/- 68.26 micrograms/dl, respectively (p < 0.05). Erythrocyte vitamin E levels were significantly lower than plasma vitamin E levels in both groups. We further investigated whether a correlation exists between plasma and erythrocyte vitamin E levels and duration of diabetes, insulin dose and HbA1c measurements. However no correlation was found. In conclusion, measurement of erythrocyte vitamin E levels may be considered to be more valuable than plasma vitamin E levels in diabetic children and supplementation may be provided according to erythrocyte levels rather than plasma levels.     

Bone mineral density in malnourished children without rachitic manifestations

BACKGROUND: The purpose of this study was to determine bone mineral density (BMD) of lumbar spine in malnourished children without rachitic manifestations, before and after dietary treatment and vitamin D supplementation, and to compare with healthy children of the same community. METHODS: The subjects were 41 children with malnutrition and 21 healthy controls. None of the children had clinical, biochemical and/or radiological rickets features. The patients had moderate 15 and severe 26 malnutrition according to Gomez's criteria. Using the Wellcome Classification, marasmus was diagnosed in 16 children, kwashiorkor in 10 children. The children with malnutrition were given vitamin D supplementation. RESULTS: BMD was lower in children with malnutrition than in controls (P < 0.01). Mineralization significantly effected the severity of malnutrition (P < 0.01). BMD in kwashiorkor was similar to that of marasmus. The mean BMD level of infants receiving 400 IU of vitamin D daily was similar to that of infants receiving 800 IU of vitamin D daily at the beginning of treatment. In two supplementation groups, the BMD gradually increased during the first 3 months of treatment, but this increase in the infants receiving 800 IU of vitamin D daily was significantly higher than that in the infants receiving 400 IU of vitamin D daily. CONCLUSION: Measurements of BMD in children with malnutrition, especially severe malnutrition, are to be recommended in the initial assessment of the severity of osteopenia and in the follow up to monitor the response to therapy. Children with malnutrition should be given 800 IU of vitamin D daily. The loss of BMD must be accepted as a complication of malnutrition.     

Antioxidant status in children with homozygous thalassemia

The status of enzymatic and non-enzymatic anti-oxidants was evaluated in 41 patients with transfusion dependent beta-thalassemia. An additional 20 age-matched children, with non-hemolytic anemia, served as controls. Fresh blood samples, obtained in the morning, were processed immediately. Plasma was stored at -80 degrees C. Levels of vitamins A and E were assayed simultaneously by HPLC. RBC vitamin A was not measurable in 29 (70.7%) thalassemics and in all the controls. Plasma vitamin A levels were lower in thalassemics than in controls (p<0.05). Vitamin E in RBCs was not measurable in 13 (31. 7%) cases. The mean level of RBC vitamin E was 3 times lower in thalassemics. Similarly, SOD enzyme activity in thalassemics, was at least 1.5 lower in comparison to the activity documented in controls (p<0. 05). The observations indicate that thalassemics have enhanced oxidative stress. Administration of selective antioxidants and a balanced diet may preclude oxidative damage.     

Pulmonary function correlates with body composition in Nigerian children and young adults with sickle cell disease

Sickle cell disease (SCD) is associated with impaired growth and skeletal maturation. Decreased fat-free mass (FFM) and body fat (BF) have been reported in Nigerian children with SCD relative to healthy age- and gender-matched controls. Pulmonary abnormalities, including reduced forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)) and total lung capacity (TLC), have also been described in children with SCD. Since undernutrition is common in sub-Saharan Africa, we were interested in knowing the relationship between pulmonary function and body composition in Nigerian children and young adults with SCD. Body composition was determined using bioelectrical impedance and pulmonary function was assessed by spirometry in Nigerian children and young adults aged 7-35 years (n = 102) as well as healthy age-and gender-matched controls (n = 104). Age-adjusted data revealed 19-26% lower FFM for male (P < 0.001) and female (P < 0.001) subjects with SCD relative to the controls. FVC, FEV(1) and PEF were also significantly reduced in male and female children and young adults with SCD compared to their control counterparts. For both male and female patients and controls, FVC, FEV(1) and PEF correlated positively with FFM (P < 0.001). PEF for the female subjects with SCD diverged progressively with increasing age relative to the controls and the rate of change was significantly lower (P < 0.001). We conclude that pulmonary function is reduced in Nigerian children and young adults with SCD compared to controls and that for both groups, pulmonary function is directly related to body composition. These findings underscore the need for early nutritional intervention for children with SCD.     

孤独症谱系障碍患儿血清25(OH)D水平的检测

目的了解孤独症谱系障碍(ASD)患儿维生素D营养状况,探讨维生素D水平与ASD的关系。方法采用高效液相色谱-串联质谱法对117例新诊断的ASD患儿和109例健康对照儿童进行血清25(OH)D检测,并根据血清25(OH)D水平,将维生素D状况分为正常(30 ng/m L)、不足(10~30 ng/m L)和缺乏(10 ng/m L),比较两组儿童维生素D营养状况。结果 ASD患儿25(OH)D水平(19±9 ng/m L)明显低于对照组(36±13 ng/m L),差异有统计学意义(P0.01)。ASD患儿中维生素D缺乏和不足率为89.7%,明显高于对照组(52.3%),差异有统计学意义(P0.01)。结论 ASD患儿存在维生素D缺乏或不足,维生素D缺乏和不足有可能是ASD发病的环境/遗传因素。     

Concentration of plasma beta-carotene in cystic fibrosis children with pancreatic insufficiency

Patients with cystic fibrosis (CF) have significantly decreased plasma concentrations of antioxidant vitamins which is considered to result both from fat malabsorption and from chronic pulmonary infection. The aim of this study was to investigate levels of vitamin A and beta-carotene in plasma of CF subjects with pancreatic exocrine insufficiency. In thirty CF patients mean plasma concentrations of vitamin A (1.17 micromol/l) was lower by 30% and that of beta-carotene (1.3 micromol/l) by 60% than in healthy children. Vitamin A level was positively correlated with beta-carotene (r=0.67; p<0.001). Ratios of beta-carotene to total cholesterol and cholesterol of LDL (low density lipoprotein) were 40% lower than in the control group. We conclude that in our CF patients the concentration of beta-carotene does not seem to be sufficient to inhibit lipid peroxidation especially of LDL fraction.     

维生素D缺乏性佝偻病遗传易感性的研究

目的：遗传因素是否参与维生素D缺乏性佝偻病目前尚未明了。拟通过研究维生素D受体基因多态性与维生素D缺乏性佝偻病易感性的相关性,探讨维生素D缺乏性佝偻病的遗传易感性。方法：应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测159例维生素D缺乏性佝偻病儿童和78例正常儿童(对照组)维生素D受体(VDR)基因FokI位点的多态性,比较两组之间VDR基因型和等位基因的频率。结果：维生素D缺乏性佝偻病患儿和对照组儿童的VDR基因FokI位点基因型分布频率分别为:FF(37%),Ff(51%),ff(12%)和FF(18%),Ff(55%),ff(27%),两组之间的差异有显著性(χ20.01(2)=9.210,χ2=13.3880,P<0.01);佝偻病患儿和对照组儿童的VDR基因FokI位点等位基因分布频率分别为:F(63%),f(37%)和F(46%),f(54%),两组之间的差异有显著性(χ2=6.18,P<0.05)。佝偻病患儿F等位基因分布频率明显高于对照组人群(63%vs46%)两组之间的差异有显著性;而佝偻病患儿f等位基因频率显著低于对照组(37%vs 54%)。结论：VDR基因FokI酶切位点的多态性可能与维生素D缺乏性佝偻病的遗传易感性有关。     

Cerebrospinal fluid and plasma levels of vitamin C in children

Vitamin C (ascorbic acid) levels in cerebrospinal fluid (CSF) and plasma from 67 children, in whom lumbar puncture had to be performed for medical reasons, are reported in this preliminary paper. 14 children of this group show normal CSF laboratory values and serve as controls. Vitamin C concentrations in CSF of controls are on average 2.5-3-times higher (30.1 +/- 6.3 mg/l) than the pertaining values in their plasma (12.2 +/- 4.9 mg/l). Significant differences are exhibited by premature and term babies, which have up to 16-times higher values of vitamin C in CSF than in plasma. Furthermore CSF vitamin C is 4-5 times higher in premature babies than in schoolchildren of our group (118.2 +/- 65.9 versus 28.3 +/- 3.0 mg/l). Another interesting finding in this study is a significant decrease of CSF vitamin C in cases of acute purulent meningitis (12.3 +/- 4.8 versus 30.1 +/- 6.3 mg/l, p less than 0.05). These results, in connection with reports about high vitamin C concentrations in brain tissue, particularly in prematures, make one suspect important functions of this vitamin in physiological and pathological mechanisms in the central nervous system.     

Vitamin A,Carotin, retinolbindendes Protein und Präalbumin im Serum von Patienten mit cystischer Fibrose

Vitamin A, carotene, retinol-binding protein (RBP), and prealbumin (PA) have been measured in 42 children and adolescents with cystic fibrosis (CF) and in 92 normal controls. All patients with CF were on vitamin A palmitate in twice the dose for normals. For statistical analysis U-test of Wilcoxon, Mann and Whitney, parametric correlation coefficient and Spearman's rank correlation coefficient were used. Compared with those in normal controls mean serum concentrations of vitamin A, carotene and RBP were depressed in patients with CF (P<0.001), whereas PA levels did not differ significantly from those of normal individuals. In normal controls there was only in serum concentration of PA an elevation with age (r=0.455, P<0.001). In patients with CF, serum concentration of vitamin A decreased in correlation with age (r=?0.423,P<0.01). PA and RBP as well as RBP and vitamin A were positively related in both groups (P<0.001). In normal individuals there was a highly significant correlation between serum concentrations of vitamin A and carotene (r _s=0.606, P<0.001), whereas in patients with CF this relationship was less significant (r _s=0.311, P<0.02).     

A pilot study of prophylactic ciprofloxacin during delayed intensification in children with acute lymphoblastic leukemia

BACKGROUND: We hypothesized that prophylactic administration of an appropriate antibiotic following each delayed intensification (DI) in children with acute lymphoblastic leukemia (ALL) would reduce the episodes of fever and bacteremia associated with neutropenia, and hence reduce both the rate and duration of hospitalization. PROCEDURE: All patients in the study were treated according to a modified Medical Research Council United Kingdom ALL XI (MRC UKALL XI) protocol utilizing three DI courses. Between June and December 2000 patients received prophylactic ciprofloxacin following DI courses. The rates of hospitalization and bacteremias were compared to ALL patients who had received between one and three DI courses prior to June 2000. RESULTS: There were 69 patients who received a total of 194 DIs (controls 130; study group 64). The rate of hospitalization was 90% in the controls and 58% in the study group (P < 0.001). The median hospital stay was 10.1 days for controls and 6.0 for the study group (P < 0.001). Intensive care unit admissions were reduced from 12 to 1.5% (P = 0.02). The overall rate of proven bacteremia was reduced from 22 to 9% (P = 0.028). There were no Gram-negative bacteremias in the study group compared to 10 (7.7%) in the controls (P < 0.001). CONCLUSIONS: Compared to historical controls, patients in this study receiving prophylactic ciprofloxacin had a reduced rate and duration of hospitalization and incidence of Gram-negative bacteremia.     

Avidity of tetanus and Hib antibodies after childhood acute lymphoblastic leukaemia - implications for vaccination strategies

AIM: To investigate the possible relationship between serum levels and avidities of antibodies against tetanus toxoid (TT) and Haemophilus influenzae type b (Hib) in children that were vaccinated after treatment for childhood acute lymphoblastic leukaemia (ALL). METHODS: The study groups were 31 paediatric patients with ALL and 18 healthy controls. All subjects were vaccinated with TT and a protein conjugated Hib vaccine. Antibody levels were analysed at three time points: At diagnosis of ALL, after cessation of treatment before vaccination and three weeks after vaccination. Avidity was measured twice, with a thiocyanate elution assay, at diagnosis of ALL and three weeks after vaccination. RESULTS: There was a correlation between level and avidity of tetanus antibodies after vaccination (r(s) = 0.59, P < 0.001). In the standard-risk and intermediate-risk ALL groups, all patients responded with protective levels of tetanus antibodies with normal avidity. In the high-risk ALL group 7/9 patients had subprotective levels of tetanus antibodies after vaccination and concomitantly the lowest avidity, implying poor protection against tetanus. No patients were found with low levels and low avidity of anti-Hib IgG, and 29/31 patients had full protection after a single dose of conjugated Hib-vaccine. CONCLUSION: The vaccination strategy after childhood ALL must be different for low-risk and high-risk ALL groups, since the high-risk group fail to elicit a recall response to tetanus.     

Vitamin A status in children with asthma

Low vitamin A levels have been found in a number of diseases in children. The aim of this study was to examine the vitamin A status in children with asthma and to correlate the changes with severity of disease. Serum levels of vitamin A, retinol‐binding protein (RBP), and albumin were estimated in 35 asthmatic children (24 males) in the age group of 2–12 years (mean 5.89 years) and 29 controls (19 males). Both study and control groups were similar with respect to age, sex, and overall nutritional status. Twenty‐four children in the study group (68.6%) had moderate to severe persistent asthma and eight children had mild persistent asthma. Only three patients suffered from mild intermittent asthma. Vitamin A levels in children with asthma (mean ± SD 22.14 ± 5.38 µg/dl) were found to be significantly lower than their controls (mean ± SD 27.54 ± 4.83 µg/dl) (p = 0.0001). Age, age of onset of asthma, and gender had no correlation with serum vitamin A levels. Low serum vitamin A levels (< 20 µg/dl) were observed four times more commonly in the study group (28.6%) than controls (6.9%). Severity of asthma had a negative correlation with serum vitamin A levels (r = ? 0.61, p = 0.0001). Children with severe persistent asthma had markedly low serum vitamin A levels (mean ± SD 13.42 ± 5.19 µg/dl) as compared with mild intermittent asthma (mean ± SD 24.61 ± 2.32 µg/dl). Therapeutic trials are needed to prove whether low vitamin A levels contribute to asthma severity and the clinical utility of vitamin A supplementation in asthmatic children.     

实时荧光定量PCR检测细胞周期蛋白C在小儿急性淋巴细胞白血病中的表达

目的：应用实时荧光定量PCR（RQ-PCR）法检测人细胞周期蛋白C(CCNC)在儿童急性淋巴细胞白血病（ALL）中的表达，以探讨CCNC基因与儿童ALL的关系。方法：提取正常儿童、初治儿童ALL骨髓组织及ALL细胞系6T-CEM的总RNA并逆转录为cDNA，应用RQ-PCR法检测CCNC的表达。结果：在正常儿童、初治儿童ALL骨髓及6T-CEM细胞系的CCNC的阳性表达率均为100%，在正常儿童CCNC基因平均相对表达强度为13.5±0.30，而在初治儿童ALL中为2.35±0.83，两者比较有统计学意义（P＜0.05）。结论： CCNC在初治ALL患儿中低表达，提示其有可能是一个抑癌基因。