Small airway patency in infants with apparent life-threatening events

A reduction in specific airway conductance has been reported in infants with a history of an apparent life-threatening event (ALTE). It is unclear, however, whether this reflects upper or lower airway narrowing. We performed a controlled study to determine small airway patency in infants with ALTE. Lung function tests were performed in 26 infants with a history of ALTE and 27 healthy controls. Partial expiratory flow-volume curves were obtained during quiet sleep using the rapid chest compression technique; thoracic gas volume (TGV) and expiratory airway resistance (RAW) were measured by whole body plethysmography. Compliance of the respiratory system (Crs) was measured using the single breath occlusion technique. The median maximal flow at functional residual capacity (V˙_maxFRC) was 85 ml/s (range 10–198 ml/s) in patients and 123 (range 47–316 ml/s) in controls (P = 0.003). V˙_maxFRC corrected for TGV was 0.5 s⁻¹ (range 0.06–1.3 s⁻¹) and 0.9 s⁻¹ (range 0.4–1.8 s⁻¹), respectively (P = 0.001). TGV, RAW and Crs were not significantly different between patients and controls. Conclusion Reduced small airway patency may play a role in the pathogenesis of ALTE. Received: 26 November 1996 / Accepted: 20 May 1997     

Association between toll-like receptor 10 (TLR10) gene polymorphisms and childhood IgA nephropathy

Toll-like receptors (TLRs) play an important role in the induction and regulation of the innate immune system and adaptive immune responses. TLR10 gene polymorphisms have been reported to be associated with a range of immune-related diseases. In this study, we investigated the association of TLR10 gene polymorphisms with immunoglobulin A nephropathy (IgAN) in Korean children. To examine the association, we genotyped one promoter single nucleotide polymorphisms (SNP) [rs10004195 (−113T/A)] and three missense SNPs [rs11096957 (Asn241His), rs11096955 (Ile369Leu), and rs4129009 (Ile775Val)] using direct sequencing in 199 IgAN patients and 289 control subjects. Our case–control analysis showed that rs10004195 was associated with IgAN (codominant model, p = 0.016 in TT vs. TA; p = 0.044 in TT vs. AA; dominant model, p = 0.0068). In addition, when comparing the proteinuria level of IgAN patients according to the genotypes of each SNP, we found that in dominant model of rs1004195, the level of proteinuria of patients with TA or AA genotypes (median, 4.01 mg/m²/h) was higher than that of patients with TT genotype (2.00 mg/m²/h, p = 0.033). In conclusion, these results suggest that TLR10 gene may be associated with susceptibility to IgAN in Korean children.     

Contribution of the blood glucose level in perinatal asphyxia

This is a comparative study between 60 asphyxiated newborns (cases) and 60 normal neonates (controls) in respect of their plasma glucose and uric acid levels and also their clinical and neurological status. The mean plasma glucose level was significantly lower (35.1 ± 11.4 mg/dl vs. 56.9 ± 5.5 mg/dl; P < 0.001) and the mean serum uric acid level was higher (8.0 ± 1.2 mg/dl vs. 4.5 ± 0.83 mg/dl; P < 0.001) in the asphyxiated group when compared to the controls. Within the perinatal asphyxia group, the plasma glucose level and Apgar scores showed a significant positive linear correlation (r = 0.740, P < 0.001), whereas a significant negative linear correlation was observed between the glucose level and different stages of hypoxic ischemic encephalopathy (HIE) (r = −0.875, P < 0.001). Although a strong positive linear correlation was found between uric acid and HIE stages (r = 0.734, P ≤ 0.001), the linear correlation between uric acid and Apgar scores (r = −0.885, P < 0.001) and uric acid and the plasma glucose level (r = −0.725, P < 0.001) were found to be significantly negative among the cases. Conclusion: The severity of encephalopathy and cellular damage varies with the severity of hypoglycemia.     

Caloric intake and weight gain in a neonatal intensive care unit

The aim of this paper was to study the weight gain in very-low-birthweight (VLBW) infants by adopting earlier and higher intake of proteins and earlier intake of lipids. We studied 28 VLBW infants admitted to Neonatal Intensive Care Unit during the year 2004 (group 1) and 18 during the first semester of 2006 (group 2). Dietary intakes for group 1 were: 1 g kg⁻¹ day⁻¹ of proteins started at postnatal day 2 (P2) and 0.5–1 g kg⁻¹ day⁻¹ of lipids at P3; for group 2, 1–1.5 g kg⁻¹ day⁻¹ of proteins and 0.5–1 g kg⁻¹ day⁻¹ of lipids, both started at P1. Caloric intake was significantly higher in group 2 (p < 0.05), whereas cumulative nutritional deficit was higher in group 1 (p ≤ 0.01). Weight z scores were significantly lower at discharge comparing with z scores at birth for each group (p ≤ 0.01), with no differences between the two groups. Despite a higher protein intake which resulted in a lower nutritional deficit, the weight z score did not improve significantly at discharge.     

Left ventricle output and mean arterial blood pressure in preterm infants during the 1st day of life

The objective was to assess the contribution of left ventricular output (LVO) in determining low mean arterial blood pressure (MABP) in preterm infants admitted to the neonatal intensive care unit. Doppler echocardiography was prospectively performed on a cohort of 17 consecutive infants with low MABP (<30 mmHg) and on 17 consecutive control subjects (range: 600–1520 g; 27–30.7 weeks gestation). The median haematocrit was 42.5% in the low MABP group versus 49.4% in the control group (P < 0.01). The index of resistance to the LVO (RILV = MABP:LVO ratio) was lower in the low MABP group (98 vs 156 mmHg · l⁻¹ · kg⁻¹ · min⁻¹; P < 0.05). An analysis of the low MABP group regarding LVO revealed that a subgroup of four infants had LVO <10th percentile (185 ml · kg⁻¹ · min⁻¹) with a high RILV (>90th percentile: 226 mmHg · l⁻¹ · kg⁻¹ ·  min⁻¹) for three of the infants. The remaining 13 infants had LVO >10th percentile and a shortening fraction >25th percentile. In this subgroup, a high proportion of infants (9/13 vs 2/17, P < 0.01) had low RILV (<10th percentile: 96 mmHg · l⁻¹ · kg⁻¹ · min⁻¹) and the incidence of haemodynamically significant patent ductus arteriosus was higher than in the control group (10/13 vs 4/17, P < 0.01). Conclusion Left ventricular output, index of resistance to left ventricular output and patent ductus arteriosus status are important to consider in evaluating mean arterial blood pressure during early postnatal life in preterm infants. Low mean arterial blood pressure is frequently associated with normal or high left ventricular output, low index of resistance to left ventricular output and significant patent ductus arteriosus. Received: 10 November 1998 and in revised form: 8 February 1999 / Accepted: 9 February 1999     

The prevalence and etiology of anemia among HIV-infected children in India

In this report, the prevalence and multifactorial etiology of anemia among Indian human immunodeficiency virus (HIV)-infected children are described. HIV-infected children aged 2–12 years were prospectively enrolled in 2007–2008. Measured parameters included serum ferritin, vitamin B₁₂, red-cell folate, soluble transferrin receptor, and C-reactive protein. Children received antiretroviral therapy (ART), iron and, folate supplements as per standard of care. Among 80 enrolled HIV-infected children (mean age 6.8 years), the prevalence of anemia was 52.5%. Etiology of anemia was found to be iron deficiency alone in 38.1%, anemia of inflammation alone in 38.1%, combined iron deficiency and anemia of inflammation alone in 7.1%, vitamin B₁₂ deficiency in 7.1%, and others in 9.5%. Median iron intake was 5.7 mg/day (recommended dietary allowance 18–26 mg/day). Compared to nonanemic children, anemic children were more likely to be underweight (weight Z-score −2.5 vs. -1.9), stunted (height Z-score −2.6 vs. -1.9), with lower CD4 counts (18% vs. 24%, p < 0.01), and higher log viral load (11.1 vs. 7.1, p < 0.01). Hemoglobin (Hb) improved significantly among those who started ART (baseline Hb 11.6 g/dl, 6-month Hb 12.2 g/dl, p = 0.03). Children taking ART combined with iron supplements experienced a larger increase in Hb compared to those receiving neither ART nor iron supplements (mean Hb change 1.5 g/dl, p < 0.01). Conclusion Anemia, particularly iron deficiency anemia and anemia of inflammation, is highly prevalent among children with HIV infection. Micronutrient supplements combined with ART improved anemia in HIV-infected children.     

Lipoprotein lipase gene polymorphisms and risks of childhood obesity in Chinese preschool children

Childhood obesity is increasingly prevalent in the community and is related to many adult diseases. Lipoprotein lipase (LPL) plays a central role in dyslipidemia, and polymorphisms of the LPL gene may result in the disturbance in the lipid’s metabolism. The aim of this study is to test the hypothesis that genetic variants of LPL and serum lipid levels are associated with the risk of childhood obesity. We genotyped +495T > G and PvuII T > C in an LPL gene and measured the serum lipid levels in a case–control study of 124 obese children and 346 frequency-matched normal controls in preschool Chinese children. The variant genotypes of LPL +495GG and PvuII CC were associated with a significantly increased risk of childhood obesity [adjusted odds ratio (OR) = 2.39, 95% CI = 1.09–5.23 for +495 GG; adjusted OR = 2.00, 95% CI = 1.04–3.83 for PvuII CC], compared with their wild-type genotypes, respectively. In addition, compared with the lower serum level cut off by the control median, the higher level of serum triglyceride (TG) (>0.59 mmol/L) was associated with a 1.32-fold increased risk of childhood obesity, and the higher level of high density lipoprotein cholesterol (HDLC) (>1.14 mmol/L) was associated with a 36% decrease in risk of childhood obesity. Furthermore, the median levels of TG were higher in obese children carrying LPL +495TT/TG and PvuII TT/CT genotypes than those in controls, the HDLC levels were lower in obese children carrying LPL +495TG and PvuII CT/CC genotypes than those in controls. In conclusion, the LPL gene +495T > G and PvuII T > C polymorphisms may modulate the magnitude of dyslipidemia in Chinese early-onset obesity.     

Evaluation of tumour necrosis during chemotherapy with diffusion-weighted MR imaging: preliminary results in osteosarcomas

Background During successful chemotherapy of osteosarcomas tumour size does not diminish significantly because the therapy has limited impact on the mineralized matrix of the tumour. Treatment response is considered successful if, histologically, more than 90% of tumour cells show necrosis. Objective To determine if osteosarcomas change their water diffusion during preoperative chemotherapy in relation to the amount of tumour necrosis. Materials and Methods Eight patients (age 11–19 years) with histologically proven limb osteosarcoma underwent T1-weighted, fat-suppressed T2-weighted and contrast-enhanced T1-weighted spin-echo imaging together with diffusion-weighted EPI sequences (b = 700) at 1.5 T before and after five cycles of standard chemotherapy. Tumour volume and apparent diffusion coefficient (ADC) maps were calculated before and after chemotherapy. The degree of tumour necrosis after chemotherapy was assessed using the histological Salzer-Kuntschik classification (grades 1–6). Results During chemotherapy, the ADC values of osteosarcomas changed significantly. The ADC of untreated tumour was 2.1 ± 0.4 × 10⁻³ mm²/s (mean ± SD) (95% CI 1.6–2.0). The ADC of chemotherapy-treated sarcomas was 2.5 ± 0.4 × 10⁻³ mm²/s (95% CI 1.8–2.2). Necrotic areas, which were confirmed by macroscopic examination, showed ADC values up to 2.7 × 10⁻³ mm²/s. Four patients with little viable tumour tissue within the neoplasm (Salzer-Kuntschik grades 1–2) had an increase in ADC of 0.4 up to 0.7 × 10⁻³ mm²/s. Four patients with larger areas of viable tumour (Salzer-Kuntschik grade 4) showed a lesser increase in ADC of 0.0 up to 0.3 × 10⁻³ mm²/s. The differences in ADC values in tumour tissue before and after chemotherapy were highly significant (P = 0.01). Conclusion During chemotherapy of osteosarcomas, tumour ADC changes are related to the degree of tumour necrosis. Supported by Grant DFG# u103     

Serum vascular endothelial growth factor: a new predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease

We investigated serum vascular endothelial growth factor (SVEGF) levels in Kawasaki disease and determined whether these levels had any association with the development of coronary artery lesions. We measured SVEGF levels in 66 patients with Kawasaki disease, 18 patients with active infections and 18 afebrile controls. SVEGF levels of patients in the acute phase of Kawasaki disease (0.0–2003.6 pg/ml, median 59.87 pg/ml) were significantly higher than those of patients with active infections (0.0–45.2 pg/ml, median 8.10 pg/ml; P < 0.05) or afebrile controls (0.0–49.8 pg/ml, median 7.75 pg/ml; P < 0.05) and decreased to undetectable or low levels in the recovery phase (n=31, acute phase: 0.0–2003.6 pg/ml, median 62.50 pg/ml versus recovery phase: 0.0–146.5 pg/ml, median 26.90 pg/ml; P=0.0007) of the disease. There existed a positive correlation between SVEGF levels and serum C-reactive protein concentrations in the acute phase of Kawasaki disease (r _s =0.347, P=0.0051). In addition, SVEGF level and duration of fever were found to be major risk factors for the occurrence of coronary artery lesions by univariate (P=0.012 and P=0.003, respectively) and multivariate (P=0.037, OR 6.16 and P=0.0059, OR 7.59, respectively) analyses. Conclusion Serum vascular endothelial growth factor level, in combination with persistence of fever, could be a powerful predictor for the development of coronary aneurysms. Received: 16 March 1999 / Accepted: 30 November 1999     

Glutamine attenuates TPN-associated liver injury in infant rabbits

The aim of this study was to assess the effects of parenteral alanyl-glutamine dipeptide (Ala-Gln) on TPN-associated liver injury. Forty-three New Zealand rabbits (6–8 days old) were divided into three groups: 12 in the control group (maternal fed); 18 in the TPN group (TPN for 10 days); 13 in the Gln-PN group (TPN+Ala-Gln 400 mg kg⁻¹ day⁻¹ for 10 days). At the end of the experiment, liver function and histology were evaluated; MDA content of liver tissues and hepatocyte apoptosis by TUNEL assay were also determined. The serum concentration of direct bilirubin and bile acid in the Gln-PN group was significantly lower than TPN group (P < 0.05), but showed no difference compared with the control group. AST level of the Gln-PN group was lower than the other two groups. The light microscopy (LM) features in the TPN group included cholestasis or diffuse steatosis, while in the Gln-PN group, inflammatory infiltration and mild hydropic degenerative changes were mainly found without obvious cholestasis or proliferation of bile ducts. The electron microscopy appearances corresponded with LM findings. The liver MDA content in the Gln-PN group was clearly lower than the TPN group (P < 0.05), and was lower without statistical significance compared with control group. TUNEL assays showed the ratio of apoptotic hepatocytes in the TPN group was the highest among all the groups (44.59 ± 6.68 vs. 0.92 ± 0.85 in the control group, P < 0.01; 44.59 ± 6.68 vs. 4.14 ± 2.76 in the Gln-PN group, P < 0.01). There were significantly fewer apoptotic hepatocytes in the Gln-PN group. From this study, we found that glutamine dipeptide supplementation could attenuate TPN-associated liver injury in infant rabbits, and could also decrease liver MDA production and hepatocyte apoptosis during total parenteral nutrition. This study was supported in part by the National Key Program Grant (No.2004BA709B09).     

Serum osteocalcin has limited usefulness as a diagnostic marker for rickets

Serum alkaline phosphatase (AP), the bone fraction of which is secreted by osteoblasts, is elevated in rickets. Both normal and elevated levels of serum osteocalcin (OC), a bone-specific marker secreted by osteoblasts, have been reported in rickets. Expression of the OC gene is enhanced by 1,25-dihydroxyvitamin D (1,25(OH)₂D) in experimental models. This study assessed serum OC levels in 14 controls and 41 patients with active rickets divided into a phosphopenic (n=20) and a calciopenic (n=21) group. Phosphopenic subjects were older (9.5 versus 5.7 years, P=0.03) with higher median serum calcium level (2.35 versus 2.16 mmol/l, P=0.0002) and serum 25-hydroxyvitamin D level (15.4 versus 10.4 ng/l, P=0.003); and lower serum phosphate (0.80 versus 1.51 mmol/l, P=0.0001), serum 1,25(OH)₂D (43.0 versus 95.6 pg/ml, P=0.0001) and intact serum parathyroid hormone level (45.0 versus 141.5 ng/l, P=0.01) than calciopenic subjects. There were no differences in median serum AP (774 versus 1430 IU/l, P=0.17) and OC (14.5 versus 13.4 ng/ml, P=0.6) between the two groups. The mean OC value for the 41 rickets subjects was 15.1 ± 6.2 ng/ml and 17.4 ± 7.8 ng/ml for the 14 control subjects. In the face of markedly elevated serum AP levels in the rickets subjects, all of the serum OC values in the study fell within two standard deviations of the mean for normals. There was no association between serum OC and 1,25-(OH)₂D in either the phosphopenic or the calciopenic group. Conclusion These results show that serum osteocalcin levels are not elevated in all forms of active rickets and that, unlike serum alkaline phosphatase, serum osteocalcin cannot be used in the diagnosis of rickets. Received: 24 September 1999 / Accepted: 23 March 2000     

Normal saline is a safe initial rehydration fluid in children with diarrhea-related hypernatremia

To demonstrate safety and efficacy of using normal saline (NS) for initial volume expansion (IVE) and rehydration in children with diarrhea-related hypernatremic dehydration (DR-HD), forty eight patients with DR-HD were retrospectively studied. NS was used as needed for IVE and for initial rehydration. Fluid deficit was given over 48 h. Median Na⁺ level on admission was 162.9 mEq/L (IQR 160.8–165.8). The median average hourly drop at 6 and 24 h was 0.53 mEq/L/h (0.48–0.59) and 0.52 mEq/L/h (0.47–0.57), respectively. Compared to children not needing IVE, receiving ≥40 ml/kg IVE was associated with a higher average hourly drop of Na⁺ at 6 h (0.51 vs. 0.58 mEq/L/h, p = 0.013) but not at 24 h (p = 0.663). The three patients (6.3%) with seizures had a higher average hourly drop of Na⁺ at 6 and 24 h (p = 0.084 and 0.021, respectively). Mortality (4/48, 8.3%) was not related to Na⁺ on admission or to its average hourly drop at 6 or 24 h. Children receiving ≥40 ml/kg IVE were more likely to die (OR 3.3; CI, 1.5–7.2). Conclusion: In children with DR-HD, NS is a safe rehydration fluid with a satisfactory rate of Na⁺ drop and relatively low incidence of morbidity and mortality. Judicious use of IVE should be exerted and closer monitoring should be guaranteed for children requiring large volumes for IVE and for those showing rapid initial drop of serum Na⁺ to avoid neurological complications and poor outcome.     

Complicated parapneumonic effusion in Belgian children: increased occurrence before routine pneumococcal vaccine implementation

An increased occurrence of complicated parapneumonic effusions in children has been reported from the UK and USA. Data from mainland Europe are scarce. We investigated the incidence of complicated parapneumonic effusion and empyaema in children admitted to the University Hospital of Leuven between 1993 and 2005, an era when pneumococcal conjugated vaccination had not yet been implemented. Sixty-eight cases were identified. The incidence increased from 20–55/100,000 hospital admissions to 120–130/100,000 hospital admissions in 2005, with 50% of the cases occurring from 2003 onwards (late cohort). This increase occurred later than that reported in the UK and US, but is of similar magnitude. The median patient age was 3.6 years (range 0.5–17 years). The median duration of symptoms before admission was 4 days (quartile values 3–7 days). The median white blood cell (WBC) count was 15,450 WBC/mm³ (quartile values 11,300–21,200 WBC/mm³) and the median C-reactive protein (CRP) level was 242 mg/L (quartile values 143–344 mg/L). Patients in the late cohort seemed to have worse disease compared to early cohort patients; significantly higher pleural lactate dehydrogenase (LDH) level (P = 0,02), higher pleural WBC, lower pleural glucose level and significantly longer duration of hospitalisation in the later cohort (P < 0,05), possibly reflecting more severe disease. In both cohorts, Streptococcus pneumoniae was the most frequently isolated pathogen, with serogroup 1 prevailing. The occurrence of complicated parapneumonic effusion increased in Belgian children before pneumococcal vaccination was added to routine childhood immunisations. This increase is pronounced from 2003 onwards (late cohort) and, thus, occurred later than that reported in the UK and USA; several parameters point towards the occurrence of more serious disease in the late cohort patients. Tine Van Ackere and Marijke Proesmans contributed equally to this paper and are the first authors.     

Arterial distensibility is reduced in overweight pre- and early pubescent children

The objective of this study was to examine the differences in arterial distensibility between overweight/obese and normal weight pre- and early pubescent boys and girls. Arterial distensibility was measured in 65 children (43 normal weight and 22 overweight/obese) between the ages of 9 and 12 years. Weight classification was based on age and sex-specific body mass index (BMI) cut-offs and pubertal maturation by Tanner staging. Distensibility was determined using B-Mode echo-Doppler ultrasound to measure changes in the right common carotid artery (CCA) diameter, while carotid pulse pressure was measured at the left CCA by applanation tonometry. Accounting for age and sex (ANCOVA), CCA distensibility showed a significant difference (P < 0.05) between normal weight (0.79 ± 0.21) and overweight children (0.61 ± 0.21 mmHg⁻¹ × 10⁻²). Univariate analysis revealed that CCA distensibility was related to BMI, systolic blood pressure, brachial pulse pressure, and relative oxygen uptake (VO_2peak, milliliter per kilogram per minute). Multivariate analysis revealed that, when adjusting for brachial pulse pressure and relative VO_2peak, differences in CCA distensibility by BMI were no longer significant. This study demonstrates that attenuated arterial distensibility exists in overweight pre- and early pubescent children. As well, this study highlights the influential role of blood pressure and aerobic fitness on arterial distensibility.     

Serum D-lactate levels as a predictor of intestinal ischemia-reperfusion injury

Currently, no serum marker has proved helpful in diagnosing intestinal ischemia and reperfusion (I/R) injury. An experimental study was conducted to determine the value of serum D-lactate in detecting intestinal I/R injury. Thirty New Zealand White rabbits were divided into three groups of 10 animals each: sham-operation controls (S); I/R; and I/R plus mannitol treatment (M). Serum samples were obtained before operation (T₀), at the end of the ischemic period (T₁), after the first 30 min of reperfusion (T₂), and at the end of the reperfusion period (T₃). In Group S, mean D-lactate levels for T₀, T₁, and T₂ were 0 μg/dl, while T₃ was 5.8 ± 4.7 μg/dl. Before the operation (T₀), serum mean D-lactate levels were 0 μg/dl in all groups (S, I/R, M). Levels increased after 1 h of ischemia (T₁) in groups I/R (83.5 ± 25.6 μg/dl) and M (89.8 ± 19.9 μg/dl), but not in group S (0 μg/dl). The mean T₂ level in group I/R (231.6 ± 78.6 μg/dl) was statistically higher than in group M (140.1 ± 53.5 μg/dl) (P = 0.007). At the end of the reperfusion period, the mean T₃ level in group I/R (698.4 ± 360.4 μg/dl) was significantly higher than in group M (158.7 ± 61.4 μg/dl) (P = 0.000). In group I/R, mean D-lactate levels changed significantly at each time point (T₁ vs T₂, P = 0.001; T₂ vs T₃, P = 0.004). However, in group M the increase from T₁ to T₂ was significant (P = 0.012), but that from T₂ to T₃ was not (P = 0.293). As a result, the mean T₃ level was significantly higher than the T₂ level in group I/R (P = 0.004), but not in group M. This study confirmed a significance rise in D-lactate levels in animals with I/R injury compared to sham-operated and I/R injury plus M treatment. We suggest that serum D-lactate levels could be a useful marker of intestinal I/R injury before laparatomy. Accepted: 26 May 1998     

Effect of central precocious puberty and gonadotropin-releasing hormone analogue treatment on peak bone mass and final height in females

To evaluate the effect of central precocious puberty (CPP) and its treatment with gonadotropin-releasing hormone (GnRH) analogues on final height and peak bone mass (PBM), we measured lumbar bone mineral density (BMD) in 23 girls at final height. Patients were distributed in two groups. Group 1: 14 patients with progressive CPP were treated with GnRH analogues; seven patients received buserelin (1600 μg/daily), subsequently switched to depot triptorelin (60 μg/kg/26–28 days); seven patients were treated with depot triptorelin (60 μg/kg/26–28 days); mean age of treatment was 6.2 years (range 2.7–7.8 years); the treatment was discontinued at the mean age of 10.1 years (range 8.7–11.3 years); final height was reached at the mean age 13.4 years (range 12.0–14.9 years). Group 2: 9 patients (mean age 6.5 years, range 4.8–7.7 years) with a slowly progressing variant of CPP were followed without treatment; final height was reached at the mean␣age␣13.6 years (range 12.5–14.8 years). Lumbar BMD (L₂-L₄ by dual energy X-ray␣absorptiometry) was measured in all patients at final height. In group 1, final height␣(158.9 ± 5.4 cm) was significantly greater than the pre-treatment predicted height (153.5 ± 7.2 cm, P < 0.001), but significantly lower than mid-parental height (163.2 ± 6.2 cm, P < 0.005). Subdividing the girls of group 1 according to the bone age at discontinuation of therapy (i.e. ≤11.5 years, n = 5, or ≥12.0 years, n = 9), the former patients had a final height significantly higher than the latter (163.7 ± 3.9 cm vs 156.5 ± 4.6 cm, P < 0.02). In group 2, final height (161.8 ± 4.6 cm) was similar to the pre-treatment predicted height (163.1 ± 6.2 cm, P = NS) and was not significantly different from mid-parental height (161.0 ± 5.9 cm). BMD values (group 1: 1.11 ± 0.14 g/cm², group 2: 1.22 ± 0.08 g/cm²) were not significantly different from those of a control group (1.18 ± 0.10 g/cm²; n = 20, age 16.3–20.5 years) and the patients' mothers (group 1: 1.16 ± 0.07 g/cm², n = 11, age 32.9–45.1 years; group 2: 1.20 ± 0.08 g/cm², n = 7, age 33.5–46.5 years). In group 1, the girls who stopped therapy at a bone age ≤11.5 years had significantly higher BMD (1.22 ± 0.10 g/cm²) compared to those who discontinued therapy at a bone age ≥12.0 years (1.04 ± 0.12 g/cm², P < 0.05). Conclusion In girls with progressive CPP, long-term treatment with GnRH analogues improves final height. A subset of patients with CPP does not require treatment because good statural outcome (slowly progressing variant). In CPP, the abnormal onset of puberty and the long-term GnRH analogue treatment do not impair the achievement of PBM. In GnRH treated patients, the discontinuation of therapy at an appropriate bone age for pubertal onset may improve both final height and PBM. Received: 5 June 1997 / Accepted in revised form 21 November 1997     

Effects of a low-calorie diet on resting metabolic rate and serum tri-iodothyronine levels in obese children

The purpose of the study was to examine the effects of weight loss on resting metabolic rate (RMR) and on serum T3 levels in obese children and to investigate whether RMR changes are related to T3 changes. Sixty-four healthy, overweight, children (age: 12.1 ± 1.1 years, body mass index 29.3 ± 4.3 kg/m²) were studied during a 6-week weight reduction programme. RMR (by indirect calorimetry) total T3, total T4, TSH and fat-free mass (FFM) (by anthropometry) were measured at baseline and after 6 weeks of dietary treatment. Weight loss resulted in a 10.1% decline in RMR (P < 0.01) and a 23.4% decrease in serum T3 levels (P < 0.001). RMR was correlated with FFM before (r = 0.78, P < 0.001) and after weight loss (r = 0.76, P < 0.001). The changes in RMR were positively correlated with the changes in FFM (r = 0.48, P < 0.05) but also with the changes in serum T3 levels (r = 0.47, P < 0.05). The initial T3 levels predicted the subsequent fall in T3 that occurred after 6 weeks of dietary treatment (r = −0.60, P < 0.001). Conclusions A significant decrease in serum T3 concentrations and resting metabolic rate occurred as a result of a 6-week weight reduction programme in an obese child population. The decline in T3 levels combined with fat-free mass loss could be responsible for the reduction in resting metabolic rate. Received: 30 June 1998 / Accepted in revised form: 22 October 1998     

Rapid appearance and onset of action of insulin aspart in paediatric subjects with type 1 diabetes

The pharmacokinetics of the novel, rapid-acting insulin aspart were compared with those of soluble human insulin following subcutaneous administration in nine children (aged 6–12 years) and nine adolescents (aged 13–17 years) with stable type 1 diabetes. The study had a randomised, double-blind, two-period crossover design. Each patient received a single subcutaneous dose of insulin aspart or human insulin (0.15 IU/kg body weight) 5 min before breakfast and the plasma insulin and glucose concentrations were measured at intervals during the following 5 h. The pharmacokinetic profile of insulin aspart differed significantly from that of human insulin with a higher mean maximum serum insulin (C_{max ins}), 881 ± 321 (SD) pmol/l versus 422 ± 193 pmol/l for human insulin (P < 0.001); and with a shorter median serum insulin t _{max ins}, 40.0 min (interquartile range: 40–50 min) versus 75.0 min (interquartile range: 60–120 min) for human insulin, (P < 0.001). An age-related effect on C_{max ins} and area under the curve (AUC_{0–5h ins}) was observed with higher values in adolescents than in children for both insulin aspart and human insulin. Postprandial glycaemic control was improved with insulin aspart; the baseline-adjusted ΔC_{max glu} being lower for insulin aspart compared with human insulin (increase of 7.6 ± 5.1 versus 9.4 ± 4.4 mmol/l respectively, P < 0.05). The incidence of adverse events was similar for the two insulin types. Conclusion The more rapid onset of action of insulin aspart versus human insulin, previously observed in adults, is confirmed in a paediatric population with type 1 diabetes. Received: 30 June 1999 and in revised form: 20 September 1999 and 23 November 1999 /Accepted: 9 December 1999     

Reduced physical activity level and cardiorespiratory fitness in children with chronic diseases

We aimed to compare physical activity level and cardiorespiratory fitness in children with different chronic diseases, such as type 1 diabetes mellitus (T1DM), obesity (OB) and juvenile idiopathic arthritis (JIA), with healthy controls (HC). We performed a cross-sectional study including 209 children: OB: n = 45, T1DM: n = 48, JIA: n = 31, and HC: n = 85. Physical activity level was assessed by accelerometer and cardiorespiratory fitness by a treadmill test. ANOVA, linear regressions and Pearson correlations were used. Children with chronic diseases had reduced total daily physical activity counts (T1DM 497 ± 54 cpm, p = 0.003; JIA 518 ± 28, p < 0.001, OB 590 ± 25, p = 0.003) and cardiorespiratory fitness (JIA 39.3 ± 1.7, p = 0.001, OB 41.7 ± 1.2, p = 0.020) compared to HC (668 ± 35 cpm; 45.3 ± 0.9 ml kg⁻¹ min⁻¹, respectively). Only 60.4% of HC, 51.6% of OB, 38.1% of JIA and 38.5% of T1DM children met the recommended daily 60 min of moderate-to-vigorous physical activity. Low cardiorespiratory fitness was associated with female gender and low daily PA. Conclusion: Children with chronic diseases had reduced physical activity and cardiorespiratory fitness. As the benefits of PA on health have been well demonstrated during growth, it should be encouraged in those children to prevent a reduction of cardiorespiratory fitness and the development of comorbidities.     

Serum asymmetric dimethylarginine (ADMA), homocysteine,vitamin B<Subscript>12</Subscript>, folate levels,and lipid profiles in epileptic children treated with valproic acid

Recent reports have demonstrated elevated serum homocysteine (Hcy) levels in children receiving valproic acid (VPA) therapy. Elevated Hcy levels might play a potential role in the resistance to antiepileptic drugs, and might lead to an increased risk for a vascular disease. It has been reported that elevated total homocysteine (tHcy) levels are associated with elevated asymmetric dimethylarginine (ADMA) levels, which are factors that may be better indicators of endothelial dysfunction compared to serum homocysteine levels, because they are less sensitive to changes, such as fasting status, physical activity, and other factors. In this study, we aim to evaluate serum ADMA, Hcy, lipid, folate, and vitamin B₁₂ levels in epileptic children, receiving VPA monotherapy. Forty-four epileptic children, receiving VPA monotherapy for at least 6 months and 28 healthy children aged between 4 and 16 years, were recruited. Serum lipids, lipoproteins, folate, vitamin B₁₂, Hcy, and ADMA levels were analyzed in both study groups. Serum Hcy, ADMA, and vitamin B₁₂ levels were higher in patients than in controls (p < 0.001 for tHcy and ADMA levels; p < 0.05 for vitamin B₁₂ levels); however, serum lipid, lipoprotein, and folate levels were similar. According to the duration of epilepsy, serum tHcy, ADMA, and triglyceride (TG) levels were higher in patients with epilepsy for ≥2 years than in patients with epilepsy for <2 years (p < 0.001 for serum ADMA levels, p < 0.01 for tHcy levels, and p < 0.05 for serum TG levels). Similarly, with respect to the duration of VPA therapy, serum tHcy, ADMA, and TG levels were higher in patients who had received VPA therapy for more than 2 years (p < 0.001 for serum ADMA levels, p < 0.05 for serum tHcy levels, p < 0.01 for TG levels). Serum ADMA levels were significantly higher in patients receiving VPA at the dose of 25–30 mg/kg/day than in those receiving 20 mg/kg/day (p < 0.01). In conclusion, our study found increased serum ADMA levels and increased tHcy levels in epileptic children receiving VPA monotherapy. Increased serum ADMA levels were demonstrated in epileptic children who have had a seizure history greater than 2 years, and have used VPA therapy for more than 2 years, and have received higher doses of VPA. Routine monitoring of serum ADMA and tHcy levels might have beneficial effects for patients receiving long-term VPA therapy, especially in children who have other potential risk factors for vascular diseases. Further studies are needed to investigate serum ADMA and Hcy levels, and the presence of vascular disease, as well as the potential interactions between serum ADMA levels and seizure control.