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     

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.     

Could lipid infusion be a risk for parenteral nutrition-associated cholestasis in low birth weight neonates?

To assess whether lipid infusion could be a risk factor for parenteral nutrition-associated cholestasis (PNAC) in low birth weight neonates, 22 newborns with cholestasis (29.8 ± 1.6 weeks, 1298 ± 217 g) were compared with 22 without cholestasis (29.5 ± 1.7 weeks, 1286 ± 363 g). The mean level of peak direct bilirubin for the cholestasis group was 4.6 mg/dl compared to 1.2 mg/dl for the noncholestasis group. A univariate analysis revealed that PNAC was significantly related to duration of fasting (p = 0.008) and parenteral nutrition (p < 0.0001), days of antibiotics use (p = 0.025), positive C-reactive protein (p = 0.018) or gastric culture (p = 0.018), and feeding intolerance (p < 0.0001). Total amino acid amount (p < 0.0001), total lipid amount (p < 0.0001), and average daily lipid amount (p = 0.002) were significantly higher in the cholestasis group than in the noncholestasis group. Conversely, prenatal administration of dexamethasone was a significant protective factor of PNAC (p = 0.008). Logistic regression analysis revealed that the cumulative amount of lipid infusion was an independent risk factor for PNAC (p = 0.041; OR 1.174; CI 1.007–1.369). We suggest that decreasing the cumulative load of amino acids and intralipids with early trophic feeding, control of infection, and prenatal administration of dexamethasone could possibly attenuate the severity of PNAC.     

Down syndrome patients with pulmonary hypertension have elevated plasma levels of asymmetric dimethylarginine

Down syndrome (DS) patients have an increased risk of developing pulmonary hypertension (PH). Increased plasma levels of asymmetric dimethylarginine (ADMA) may contribute to vascular dysfunction in adults with idiopathic pulmonary hypertension. Our goal was to test the hypothesis that DS patients with PH have higher plasma levels of ADMA than DS patients without PH. DS patients with definitive PH (n = 6) and DS patients with no evidence of PH (n = 12) were studied. Plasma levels of arginine, ADMA, and nitrite/nitrate (NOx; stable metabolites of nitric oxide (NO)) were measured. Plasma arginine concentration was lower (p < 0.05) in PH patients (23 ± 11 μM) versus non-PH patients (46 ± 24 μM). Plasma ADMA concentration was higher (p < 0.005) in PH patients (18.0 ± 4.2 μM) versus non-PH patients (8.6 ± 5.9 μM). Plasma NOx was lower (p < 0.05) in PH patients (4.5 ± 1.7 μM) versus non-PH patients (8.5 ± 7.3 μM). These results are consistent with ADMA contributing to lower NO production in DS patients with PH and suggest that ADMA levels may be a potential biomarker for PH in DS patients.     

Effect of elective antibiotic therapy on resting energy expenditure and inflammation in cystic fibrosis

Cystic fibrosis (CF) patients often present with malnutrition which may partly be due to increased resting energy expenditure (REE) secondary to inflammation. Both REE and tumour necrosis factor-alpha (TNF-α), as other markers of inflammation, are elevated during respiratory exacerbations and decrease after antibiotic treatment. However, the effect of antibiotic therapy on REE and inflammation in patients without respiratory exacerbation is not known. The aim of our study was to determine the effect of such an elective antibiotic therapy on REE, TNF-α, and other serum markers of inflammation. Twelve CF patients 5F/7M, age 15.9 ± 6.1 years, weight for height ratio 89 ± 8% without clinically obvious exacerbation and treated by intravenous antibiotics were studied. Both before (D0) and after (D14) treatment, pulmonary function tests were performed. REE was measured by indirect calorimetry and blood taken to measure inflammation parameters. Body weight increased by 1.1 kg from D0 to D14 (P < 0.001), composed of 0.3 kg fat mass and 0.8 kg fat-free mass (FFM). The forced expiratory volume at 1 s increased from 43 ± 15% of predicted at D0 to 51 ± 15% of predicted at D14 (P < 0.01). Mean REE was 41.1 ± 7.6 kcal/kg FFM per day at D0 and did not change significantly at D14 (40.6 ± 8.5 kcal/kg FFM per day). Serum markers of inflammation decreased from D0 to D14: C-reactive protein 17 ± 17 mg/l to 4 ± 7 mg/l (P < 0.05), elastase 62 ± 29 μg/l to 45 ± 18 μg/l (P < 0.02), orosomucoid acid 1.25 ± 0.11 g/l to 0.80 ± 0.15 g/l (P < 0.001), and TNF-α 37 ± 14 pg/ml to 29 ± 6 pg/ml (P = 0.05). Individual values showed a correlation between changes in REE and in TNF-α (P < 0.02). Conclusion The contribution of inflammation to energy expenditure is possible but appears to be minimal in cystic fibrosis patients treated by antibiotics on a regular basis in the absence of clinically obvious exacerbation. Received: 6 August 1998 and in revised form: 23 November 1998 / Accepted: 23 November 1998     

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     

Effect of patent ductus arteriosus and indomethacin treatment on serum cardiac troponin T levels in preterm infants with respiratory distress syndrome

Cardiac troponin T (cTnT) represents a sensitive and specific marker of ischemic myocardial damage in adult and neonatal populations. The aim of this study was to detect the potential ischemic effect of persistent patent ductus arteriosus (PDA) and indomethacin treatment on the coronary vascular bed by measuring cTnT concentrations. cTnT levels were measured in 23 preterm infants (<32 weeks of gestational age) with respiratory distress syndrome (RDS), 11 with PDA and 12 without, at 2, 4, and 7 days after birth. cTnT concentrations (mean ± SEM) significantly decreased (P < 0.05) from the 2nd (0.63 ± 0.09 μg/l) and the 4th (0.77 ± 0.13 μg/l) to the 7th postnatal day (0.28 ± 0.04 μg/l). At day 2 after birth, cTnT levels in preterm infants with RDS were significantly higher (P < 0.05) than our reference values for healthy preterm neonates (0.63 ± 0.09 μg/l vs 0.18 ± 0.04 μg/l). No differences were found between RDS infants with and without PDA at 2 (0.65 ± 0.13 vs 0.61 ± 0.14 μg/l), 4 (0.71 ± 0.21 vs 0.87 ± 0.16 μg/l), and 7 (0.26 ± 0.05 vs 0.29 ± 0.07 μg/l) days of life. In infants with PDA, cTnT levels did not differ before the first dose of indomethacin was given (0.65 ± 0.14 μg/l) or 2 h (0.65 ± 0.15 μg/l) and 48 h (0.71 ± 0.21 μg/l) afterwards. Conclusion In preterm infants with RDS the occurrence of PDA and indomethacin treatment are not associated with ischemic cardiac damage as detected by cTnT measurements. Received: 23 December 1998 and in revised form: 4 May 1999 / Accepted: 11 October 1999     

Manganese elevations in blood of children with congenital portosystemic shunts

Magnetic response imaging has demonstrated increased signal intensities within the basal ganglia in patients with hepatic encephalopathy; the densities are considered to represent manganese deposition. We measured whole blood manganese concentrations in nine children with congenital portosystemic venous shunts detected by screening tests for galactosaemia. Beyond 1 year of age, these patients showed significantly higher manganese concentrations than controls (2.40 ± 0.43 versus 1.48 ± 0.38 μg/dl; P=0.0001). Four of the nine patients were studied by magnetic response imaging. T1-weighted images showed increased signal intensities in the basal ganglia of those four patients, suggesting manganese accumulation. Conclusion Children with congenital portosystemic venous shunts showed manganese elevations in blood and magnetic response imaging changes in the basal ganglia. These children should avoid excessive manganese intake. Received: 11 September 2000 / Accepted: 30 November 2000     

Inhibition of the Na<Superscript>+</Superscript>/H<Superscript>+</Superscript> Exchanger Protects the Immature Rabbit Myocardium From Ischemia and Reperfusion Injury

Background This study investigated the cardioprotective effects of pharmacologic pretreatment with HOE642, a selective Na⁺/H⁺ exchanger (NHE) isoform-1 inhibitor, in immature rabbit hearts, as compared with ischemic preconditioning (IPC). Methods For this study, 36 isolated immature New Zealand white rabbit hearts were equilibrated on the Langendorff apparatus. They were randomly divided into three groups: control group, IPC group, and HOE642 group. The hearts in each group were subjected to 60 min of ischemia plus 60 min of reperfusion (I/R). In the IPC group, the hearts were preconditioned by 5 min of ischemia followed by 10 min of reperfusion before I/R. In the HOE642 group, the hearts were pretreated with HOE642 (5 μmol/l) for 15 min before I/R. Left ventricular performance (LVDP, +dp/dt_max, −dp/dt_max), coronory artery flow (CF), myocardial water content, adenosine triphosphate (ATP), cardiac-specific enzymes (creatine kinase [CK], CK fraction MB [CK-MB], and lacate dehydrogenase [LDH]), and intracellular calcium content were measured. Myocardial ultrastructure was observed under transmission electron microscopy. Results The recovery rates for left ventricular performance and CF in both the HOE642 and the IPC groups increased compared with those for the control subjects (p < 0.05). Moreover, the recovery rates for LVDP, +dp/dt_max, −dp/dt_max, and CF in the HOE642 group were markedly higher than in the IPC group at most time points of reperfusion (p < 0.05). Compared with the control group, CK, CK-MB, and LDH in the HOE642 group were decreased significantly (p < 0.05), whereas only LDH was reduced in the IPC group (p < 0.05). Water content was significantly reduced and ATP reserve was significantly increased in both the IPC and HOE642 groups (p < 0.05). However, compared with the IPC group, water content in the HOE642 group was significantly lower (81.26% ± 1.26% vs 83.58% ± 1.27%; p < 0.05) and ATP was significantly higher (21.46 ± 2.40 vs 17.66 ± 1.50 μg/g; p < 0.05). The HOE642 pretreatment exerted a better effect of reducing calcium overload than IPC (265.8 ± 41.1 vs 408.5 ± 56.8 mg/kg dry weight; p < 0.05). The blinded ultrastructural assessment under transmission electron microscopy showed that HOE642 brought about more myocyte salvage than IPC. Conclusion This study demonstrated that HOE642 pretreatment is superior to IPC against ischemia and reperfusion injury in isolated immature rabbit myocardium.     

Effect of antioxidant therapy on collagen synthesis in corrosive esophageal burns

To investigate the efficacy of antioxidant therapy on collagen synthesis in corrosive esophageal burns, 110 Sprague-Dawley rats were divided into five groups of 22 animals each. A standard esophageal caustic burn was produced by 1 ml of 10% sodium hydroxide solution for the rats in groups B to E; group A was instilled only with 0.9% saline after preparation of the distal esophageal segment. Group A animals (controls) were uninjured and untreated. Group B had untreated esophageal burns. Esophageal burns were treated in group C with vitamin E (10 mg/kg IM), in group D with vitamin C (10 mg/kg IP), and in group E with methylprednisolone (30 mg/kg IM) on each of 5 days. Eight rats from each group were killed 4 days after initiation of the study and the abdominal esophagus was studied for tissue malondialdehyde (MDA; μmol/g protein) levels. The other rats were killed 28 days after initiation of the study and determination of hydroxyproline (HP) (μg/g tissue) levels in esophageal tissue was performed for 8 rats in each group. Histopathologic evaluation was also performed in the other 6 rats from each group. MDA levels in esophageal tissue were significantly lower in groups C (9.24 ± 2.62, P < 0.01) and group E (6.26 ± 2.22, P < 0.001) than in group B (12.35 ± 1.80). HP levels were significantly lower in groups A (0.75 ± 0.21, P < 0.001), C (1.11 ± 0.15, P < 0.01), and E (0.96 ± 0.15, P < 0.001) than in group B (1.40 ± 0.20). Histopathologically, collagen deposition in the submucosa and tunica muscularis was lower in groups C and E than in group B (P < 0.05, and 0.01, respectively). Our results demonstrate that treatment with antioxidant drugs such as vitamin E and methylprednisolone decreased tissue HP levels, and thus inhibited new collagen synthesis and stricture formation in rats with alkali-induced caustic esophageal burns. Accepted: 16 February 2001     

Preventive effect of 2 and 10 mg of sodium cromoglycate on exercise-induced bronchoconstriction

This double-blind, randomised and cross-over study was designed to compare the preventive effect against exercise-induced bronchoconstriction (EIB), defined as the percentage decrease in FEV₁≥15% after 6 min of exercise, of 2 mg and 10 mg of sodium cromoglycate (SCG), administered through a metered dose inhaler via spacer, in asthmatic children. Each of the 30 subject (age 11.6 ± 3.2 years) was tested on five occasions. For inclusion, EIB in test1 was required. In tests 2 to 5, all subjects inhaled 2 mg or 10 mg of SCG 20 min and 120 min before exercise in a randomised order. In order to assess excretion of eosinophil protein X (EPX) accompanying EIB, urine samples were collected before and after exercise. The mean percentage fall in FEV₁ (±SD) in test 1 was 26.8 ± 9.8%. Inhalation of 2 mg and 10 mg of SCG 20 min before exercise provided a significant preventive effect in 83% and 77% and inhalation 120 min before exercise provided a preventive effect in 63% and 70%, respectively (n=30). Variance analysis did not reveal a statistically different absolute fall in FEV₁ after exercise when both doses (120 min before exercise) were compared (P=0.356). In an unselected subgroup of 12 children, urinary EPX increased after the challenge without SCG premedication (test 1) (mean change: +48.7 μg/mmol creatinine, P=0.034), whereas no significant increase was found in case of SCG premedication (mean change in μg/mmol creatinine): 2 mg/20 min: +12.1; 2 mg/120 min: +8.5; 10 mg/20 min: −10.4 and 10 mg/120 min: −23.5; P > 0.1). Conclusion Administration of 10 mg of sodium cromoglycate is no more effective in preventing exercise-induced bronchoconstriction than 2 mg regardless of whether the medication is given 20 or 120 min before exercise. The preventive effect of sodium cromoglycate on exercise-induced bronchoconstriction in asthmatic children is associated with the inhibition of urinary eosinophil protein X excretion. Received: 5 January 2000 and in revised form: 3 April and 25 April 2000 / Accepted: 26 April 2000     

Circulating soluble adhesion molecule levels in children with acute lymphoblastic leukaemia

The aim of this study was to evaluate levels of serum soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) as parameters of disease activity and to monitor the response to treatment in children with acute lymphoblastic leukaemia (ALL). The above soluble adhesion molecules were determined in the serum of 35 children with ALL and 30 healthy children (control group) of the same age range. The samples were obtained before treatment, 6 months after the beginning of the treatment (remission of the disease), 6 months after the end of the treatment and during relapse of the disease. The mean levels of sICAM-1, sVCAM-1 and sE-selectin at the onset of the disease were 646.6 ± 80.9 ng/ml, 1786 ± 151.8 ng/ml and 140.5 ± 17.3 ng/ml, respectively. These values were significantly higher (P < 0.001) than those of the control group, which were, 245.8 ± 25.7 ng/ml, 798.6 ± 78.9 ng/ml and 44.7 ± 18.2 ng/ml respectively. During remission, the mean levels did not differ significantly from those of the control group. After the end of the treatment the mean levels again did not show any significant differences compared to the control group. During relapse the soluble adhesion molecule mean levels (923.9 ± 110.1 ng/ml, 2945.7 ± 349.9 ng/ml and 258.2 ± 5.1 ng/ml) were significantly higher (P < 0.001) than those of the control group and also than those obtained during remission and after the end of the treatment (P < 0.001). Pearson's correlation coefficient r was computed in order to detect possible linear correlations between: (1) sICAM-1 and sVCAM-1 (r = 0.632); (2) sICAM-1 and sE-selectin (r = 0.788) and (3) sVCAM-1 and sE-selectin (r = 0.752). All three cases correspond to P < 0.001, thus indicating strong linear correlations. Conclusion The levels of soluble circulating adhesion molecule levels can be utilized for monitoring disease activity of ALL and its response to treatment, as well as for early detection of relapse. Strong linear correlations between the three soluble adhesion molecules tested suggest that each of them may be sufficient as an indicator. Received: 5 August 1996 / Accepted: 13 February 1997     

Precision of continuous neonatal ventilator respiratory mechanics is improved with selected optimal respiratory cycles

Given their high apparent variability, bedside continuous respiratory mechanics (RM) parameters [excepting tidal volume (V _T)] remain infrequently used for adjustment of neonatal ventilatory settings. RM parameters provided by ventilator (VRC) from ten recordings of newborns [10 min in synchronised intermittent mandatory ventilation and 10 min in assist/control (A/C)] were compared to those computed from visually selected assisted leak-free optimal respiratory cycles (SRC). Mean values, variability and ability to distinguish patients were compared between VRC and SRC. Dynamic resistances were more correlated (r ² = 0.95) than compliances (r ² = 0.42). V _Ts were correlated only in A/C (r ² = 0.78). C20/C was significantly higher in VRC (1.81 ± 0.67) than in SRC (1.23 ± 0.36) and frequently out of neonatal reference range. In A/C ventilation, V _T was higher in VRC (5.6 ± 1.8 ml/kg) than in SRC (4.8 ± 1.0 ml/kg) (p < 0.05). Displayed V _Ts do not reflect those found in optimal assisted breaths and therefore have incomplete value in assessing adequacy of ventilator settings. The variability of RM parameters provided by the ventilator is large, and coefficients of variation were significantly lower with optimal respiratory cycles (for resistance, compliance, V _T and C20/C; 27%, 26%, 18%, 24% in SRC and 36%, 35%, 40% and 33% in VRC). Selecting optimal cycles yields RM with two to three times higher discriminating power between patients. Conclusion: Current ventilator’s RM parameters have limited clinical use. Using optimal breaths to calculate RM parameters improves precision and discriminating power. For integration to ventilatory care, automation of this selection must be implemented first.     

Effects of dobutamine on left ventricular performance in newborns as determined by systolic time intervals

To evaluate the effects of dobutamine on myocardial function in newborns, left ventricular systolic time intervals (STI) — normalized pre-ejection period (PEPI), normalized left ventricular ejection time (LVETI) and pre-ejection period to left ventricular ejection time ratio (PEP/LVET) — were assessed by echocardiography in 18 newborns treated with dobutamine for clinically diagnosed heart failure. Examinations were performed prior to and 30 min after starting dobutamine infusion (7.5 or 10 μg/kg per min). Patients were assigned to two groups according to their PEP/LVET prior to dobutamine administration: group I (n=9) with pre-treatment PEP/LVET ≤ 0.35 and group II (n=9) with pre-treatment PEP/LVET > 0.35. While there was no change of STI in group I, dobutamine infusion resulted in a significant decrease in PEPI (from 102±4.8 to 87.8±4.2; mean ± SEM;P<0.01) and of PEP/LVET (from 0.56±0.05 to 0.45±0.05; mean ±SEM;P<0.01) and in a significant increase of LVETI (from 237.6±5.6 to 253.3±5.2; mean ±SEM;P<0.01) in group II. Heart rate increased significantly in both groups. Left ventricular end-diastolic dimension, also assessed by echocardiography, did not change in the eight studies performed. An increase in mean arterial pressure was found in three out of five newborns of group II and in one out of four patients in group I. It is concluded that dobutamine can improve cardiac performance in newborns with impaired left venfricular function. This effect is probably due to an improvement in myocardial contractility.     

Iron metabolism in burned children

The administration of iron supplementation in children with burns has been a subject of controversy. Recent studies argue against its use in the acute phase of stress. To assess whether iron metabolism parameters show significant differences in the acute phase and the recovery phase of burn, 21 patients (age range: 17 months to 13 years) with burns of more than 10% of body surface who had not received blood transfusions or iron supplementation were studied. Sideraemia, ferritin, transferrin, transferrin saturation index (TSI) and C-reactive protein (CRP) were assessed both in the acute and the recovery phase after burn. Sideraemia, transferrin, and TSI were significantly lower in the acute than in the recovery phase (17.3 ± 3 vs 53.8 ± 6.6 μg/dL, 190.5 ± 15 vs 287.9 ± 14.3 mg/dL and 7.7 ± 1.3 vs 15.4 ± 1.6%, P < 0.0001, P < 0.001 and P = 0.0006, respectively) while plasma ferritin and CRP were significantly higher (84.7 ± 8.8 vs 43.1 ± 8.5 ng/mL and 9.5 ± 1.5 vs 0.7 ± 0.2 mg/dL, P = 0.016 and P < 0.0001, respectively). When the above parameters were analysed based on age (≤ 2 years, >2 years), the observed differences persisted. Conclusion Hyposideraemia is a frequent finding in the acute phase of paediatric burns and is accompanied by increased ferritin levels and decreased transferrin concentrations. The low iron values tend to recover without the use of iron supplementation suggesting an endogenous block of iron release in the acute phase and indicates that iron therapy should be not recommended in the initial period of stress of the burned patient. Received: 12 March 1998 / Accepted in revised form: 2 September 1998     

Are stable postoperative biliary atresia patients really stable?

 Transforming growth factor-beta 1 (TGF β-1) is an important mediator of liver-cell proliferation and replication that is implicated in hepatic fibrosis (HF). Hepatic stellate cells (HSC) are activated by TGF β-1 and are the main precursor cells involved in fibrogenesis. The correlation between serum TGF β-1, activated HSC in liver-biopsy specimens, and liver biochemistry was investigated to determine the value of TGF β-1 as an indicator of clinical status in postoperative biliary atresia (BA) patients. Thirty-two postoperative BA patients (mean age 11.2 ± 2.8 years) and 13 normal controls (mean age 10.3 ± 3.7 years) were studied. Based on average liver function test (LFT) results over a 3-month period immediately prior to this study, the BA patients were divided into group I (anicteric, normal LFT; n = 10); group II (anicteric, elevated liver transaminases; n = 12), and group III (jaundiced end-stage liver fibrosis awaiting liver transplantation; n = 10). Serum TGF β-1 was determined using ELISA. Liver-biopsy specimens were examined with antibody against TGF β-1 and α-smooth muscle actin (SMA) antibody for detection of activated HSC. Serum TGF β-1 was significantly higher in groups I (11.4 ± 3.7 ng/ml; P < 0.01) and II (23.3 ± 11.3 ng/ml; P < 0.001) than in group III (3.0 ± 1.5 ng/ml) and controls (4.5 ± 2.5 ng/ml) despite normal LFT in group I. The 3 subjects with the highest serum TGF β-1 in group II had bile lakes. Biopsies from groups I and II were strongly positive for TGF β-1 in hepatocytes and Kupffer cells and for activated HSC detected by SMA compared with group III and controls. Because serum TGF β-1 and activated HSC are only present during active fibrosis, we conclude that there is progressive fibrogenesis even in seemingly normal postoperative BA patients. In particular, bile lakes should be regarded as a key sign of progressive HF, the presence of which should be regarded with extreme caution. We suggest that serum TGF β-1 could be used as an accurate indicator of progressive fibrogenesis in postoperative BA patients. Accepted: 14 April 2000     

Study of serum zinc in neonates and their mothers in Shimla Hills (Himachal Pradesh)

Serum zinc level in cord blood of 159 neonates was estimated by atomic absorption spectrophotometer. The cases were classified according to birth weight and gestation of babies as Term appropriate for date (TAFD), Term small for date (TSFD), Term large for date (TLFD), Preterm appropriate for date (PAFD), Preterm small for date (PSFD) and Preterm large for date (PLFD). The zinc level were also estimated in mothers of these groups at the time of delivery, and compared with cord blood levels of those in non-pregnant mothers. Mean serum zinc level in infants born full term AFD, full term SFD, full term LFD, preterm AFD, preterm SFD and preterm LFD were 79.6±17.8 μg/dl, 58.2±13.4 μg/dl, 84.1±21.1 μg/dl, 81±25.2 μg/dl, 51.2±51.7 μg/dl and 76±14.7 μg/dl respectively. The maternal zinc levels in respective groups were 67±9.6 μg/dl, 56.5±7.5 μg/dl, 63.6±14.4 μg/dl, 62.7±21.1 μg/dl, 54.5±5.4 μg/dl, and 58.2±2.7 μg/dl. The mean serum zinc values in mothers and babies in birth weight group ranging from 1500–2000 gm were 55.3±4.3 μg/dl and 60±23.1 μg/dl, 2001–2500 gm were 59.5±11.3 and 65.8±17 μg/dl, 2501–3000 gm were 69.2±9.5 and 84.7±14 μg/dl, 3001–3500 gm were 65.8±12.7 μg/dl, 82.2±20.8 μg/dl and 3501 and above were 70.5±8.2 μg/dl and 85±14.3 μg/dl respectively. Statistically significant low zinc levels were observed in SFD babies and their mothers. The zinc levels in non-pregnant mothers were 82.2±11.6 μg/dl which were significantly higher from the levels obtained for pregnant mothers. Statistically significant low levels were observed in mothers as well as in babies of low birth weight group.     

The number and function of circulating endothelial progenitor cells in patients with Kawasaki disease

Kawasaki disease (KD) is associated with coronary artery injury. Studies have shown that the endothelial progenitor cell (EPC) participates in the process of arterial repair. Data have been reported that the number of EPC increased significantly in the subacute phase of KD. However, until now, there are no data about the functions of EPC in KD patients. The present study was designed to further investigate the number and functions of EPC in KD. Ten KD patients in the acute phase and ten healthy volunteers were recruited and attributed to the KD group and control group, respectively. The circulating CD34/kinase insert domain-containing receptor double positive cells were evaluated in the two groups using flow cytometry. In vitro assays were used to measure the functions of EPC, including proliferation, adhesion, and migration activities. The plasma levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP) were also assessed in both groups. The number of EPC in the KD group was significantly higher than that of the control group (0.021 ± 0.007% vs. 0.014 ± 0.003%, P < 0.05). The migratory response of EPC was significantly decreased in the KD group, compared with that of the control group (5.50 ± 1.78 vs. 3.40 ± 1.35 cells/high power field, P < 0.01). Similarly, the proliferative and adhesive activities of EPC in the KD group were also decreased (0.47 ± 0.08 vs. 0.66 ± 0.07, P < 0.01; 6.5 ± 2.12 vs. 11.2 ± 2.04 cells/high power field, P < 0.01). The plasma NO, TNF-α, and hs-CRP levels in the KD group were higher than those of the control group (54.10 ± 11.78 vs. 38.80 ± 11.10 μmol/l, P < 0.01; 48.20 ± 7.42 vs. 37.00 ± 11.12 pg/ml, P < 0.05; 87.10 ± 30.18 vs. 5.30 ± 3.37 mg/l, P < 0.01). The number of circulating EPC positively correlated with the level of NO (r = 0.92, P < 0.001), and the functions of EPC negatively correlated with the levels of TNF-α and hs-CRP, respectively. In Kawasaki disease, the number of EPC was enhanced and the functions of EPC were attenuated. The two-way regulation of circulating EPC in KD patients may be associated with the disorders of cytokines or messengers in KD patients.     

Growth hormone secretion, puberty and adult height after cranial irradiation with 18 Gy for leukaemia

The dose of prophylactic cranial irradiation given to patients for acute lymphoblastic leukaemia has been decreased from 24 to 18 Gy, but the beneficial effect of this decrease on growth is controversial. This study compares the growth hormone (GH) secretion and growth of 35 patients (20 boys) given 18 Gy at 3.7 ± 0.3 (SE) years, and routinely evaluated 5.4 ± 0.4 years after irradiation to define the indications for GH treatment in these patients. Of these, 63% had a low GH peak (<10 μg/l) after one (22 cases) or two (17 cases) stimulation tests. The plasma concentrations of insulin-like growth factor I and its GH-dependent binding protein were normal for age in all but two cases. The height changes between irradiation and evaluation were correlated with the GH peaks (P < 0.03) and were concordant, except in patients with early puberty. This occurred in 16 patients including all 12 girls irradiated before 4 years of age. A significant (P < 0.03) reduction in height (SD) between irradiation and adult height occurred in untreated GH-deficient patients (−1 ± 0.3, n = 6), but not in GH-deficient patients given GH (−0.6 ± 0.3, n = 8) or in those with normal GH peak (−0.4 ± 0.3, n = 7). Conclusion In children irradiated for acute lymphoblastic leukaemia, GH deficiency is frequent after 18 Gy but its impact on adult height is smaller than after higher doses. We suggest that the indications for gonadotropin releasing hormone analogue therapy should be broad in patients with early or rapidly progressing puberty and those for GH therapy in those patients with a below average constitutional height before irradiation. Received: 17 November 1997 / Accepted: 9 February 1998     

Thyroid function in fullterm and preterm newborns

The development of the hypothalamic-pituitary-thyroid system in the fetus occurs through three phases: thyroid pituitary embryogenesis, maturation of hypothalamus, maturation of thyroid system, neuroendocrine control and T₄ tissue deiodination. Defects in early phases I and II lead to permanent disorders whereas abnormalities in phase III result in transient functional immaturities especially in preterms. Cord serum TSH, T₄ and T₃ were estimated in 450 newborns (390 full term>36 wk gestation and 60 preterms<36 wk). The mean cord TSH of 5·069±7·4 μ U/ml in full term was lower than 7·88±3·77 μ U/ml in preterms (P<0·01). The mean cord T₄ and T₃ were significantly higher (P<0·01) 9·716±6·44 μg/dl and 0·425±0·17 ng/ml in full term as compared to preterms 6·46±3·4 and 0·355±0·16 respectively. There was significant negative correlation of serum TSH (r=−0·84 and P<0·05) and positive correlation of serum T₄ (r=0·97, P<0·001) and T₃ (r=0·89, P<0·05) with gestational age. The relationship of these hormones to weight irrespective of gestational age was more significant when compared in newborns >3 kg and <2 kg rather than in all intermediate groups. No significant differences in these hormones were evident amongst the AGA and SGA infants above and below 36 weeks gestation. Transient hypothyroxinemia, and hyper-thyrotropinemia, transient primary hypothyroidism and low T₃ syndromes are some of the transient abnormalities of thyroid function and are more commonly encountered in preterms.