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     

Phototherapy for neonatal hyperbilirubinemia affects cytokine production by peripheral blood mononuclear cells

The capacity of peripheral blood mononuclear cells (PBMC) to produce interleukin (IL) IL-1β, IL-2, IL-3, IL-6, IL-10 and tumor necrosis factor-α (TNFα) was examined in term newborns with hyperbilirubinemia after 24 hours' exposure to phototherapy (wave length 425–475 nm). The results were compared with those from untreated neonates. Fifty newborns spontaneously delivered at term were included in the study. Blood samples were collected from 20 newborns before and 24 h after phototherapy. The control group consisted of 30 neonates examined on two consecutive days. PBMC isolated from blood samples were incubated in vitro for cytokine production. The concentration of cytokines in the supernatants was tested using ELISA kits (for IL-1β, IL-6, IL-10 and TNFα), or by bioassays (for IL-2 and IL-3). Phototherapy caused a 70% increase in IL-2 secretion (123 ± 27 vs 208 ± 30 units/ml, P < 0.01) and 56% in IL-10 production (1.07 ± 0.19 vs 1.67 ± 0.33 ng/ml, P < 0.03), whereas the spontaneous secretion of IL-1β was reduced by 43% (13.7 ± 2.3 vs 7.3 ± 1.7 ng/ml, P < 0.02). In the control group the secretion of these cytokines was similar on the two consecutive days and did not differ significantly from secretion in the other group before phototherapy. On the other hand, lipopolysaccharide induced TNFα production was higher on the second day in the two groups of newborns irrespective of phototherapy (388 ± 58 vs 683 ± 88 pg/ml, P < 0.001, in the control group and 384 ± 75 vs 588 ± 91, P < 0.05, before and after phototherapy). The synthesis of IL-3 and IL-6 did not change significantly between the two days of the study. The results demonstrate that in addition to the well-known positive effect of phototherapy on the neonate serum bilirubin level, this treatment affects the function of the immune system in newborns via alterations in cytokine production. Received: 4 September 1997 / Accepted: 14 February 1998     

Immunoglobulin preparations affect hyponatremia in Kawasaki disease

Hyponatremia frequently occurs in Kawasaki disease (KD). The aim of this study was to investigate the effect of Na content of the intravenous immunoglobulin (IVIG) preparation on serum Na levels in KD. Seventy-eight subjects, of whom 27 had hyponatremia, were split up into two groups: group A receiving IVIG preparations containing high Na (0.9%) and group B receiving IVIG preparations containing trace Na. While the data before IVIG therapy revealed no significant differences in the median serum Na between the groups, an administration of IVIG preparations increased the serum levels of Na in group A (P < 0.01) but not in group B (P > 0.05). Furthermore, the median serum Na level was significantly higher in group A than that in group B (139.0 vs 137.0 mEq/L, respectively, P < 0.01). No significant difference was found in the prevalence of coronary artery lesions between the groups. In conclusion, we should keep it in mind that the IVIG products without Na have an adverse affect on hyponatremia in KD though their efficacy seems to be equivalent to those containing high Na.     

Effect of inhaled nitric oxide on intrapulmonary right-to-left-shunting in two rabbit models of saline lavage induced surfactant deficiency and meconium instillation

Marked hypoxia secondary to intrapulmonary right-to-left shunting is a characteristic of respiratory failure in human neonates and can sometimes be complicated by additional extrapulmonary right-to-left shunting. To investigate the effect of inhaled nitric oxide (iNO) on intrapulmonary shunting, two typical pulmonary diseases of the newborn (respiratory distress syndrome and meconium aspiration) were reproduced in 32 mechanically ventilated rabbits weighing approximately 2 kg each. After tracheotomy, catheters were inserted into a jugular vein, a carotid artery and the right ventricle (to measure systolic right ventricular pressure [SRVP] and mixed venous oxygen content for calculation of shunt by Fick equation). Repeated airway lavages (LAV) with normal saline or repeated instillations of a suspension of human meconium (MEC) were continued until both the a/A-ratio was ≤0.14 and a peak inspiratory pressure ≥22 mbar was needed to keep the tidal volume constant at 10 ml/kg of body weight. Measurements of shunt, SRVP, systolic systemic pressure, physiological dead space, tidal volume and a ventilation index were performed before and after completion of lung damage and at 20 and 60 min after administering iNO at 80 ppm. Four groups of rabbits were studied (n = 8 in each group): LAV control and intervention, Mec control and intervention. 60 min after starting iNO, there was a decrease in shunt (LAV: 67.6% ± [SD] 11.3% vs 56.2 ± 16.4, P = 0.05; MEC: 52.6 ± 6.3 vs 44.3 ± 8.3, P < 0.05), in SRVP (LAV: 29.7 mmHg ± 10.1 mmHg vs 20.0 ± 8.2, P < 0.01; MEC: 25.1 ± 4.4 vs 22.3 ± 5.0, P = 0.46) and in dead space (% of tidal volume, LAV: 32.7% ± 10.5% vs 25.9 ± 10.1, P < 0.01; MEC: 26.1 ± 16.6 vs 18.9 ± 10.1, P = 0.05). These results demonstrate that iNO decreases intrapulmonary shunt (as well as SRVP and dead space). We suggest that iNO may be beneficial in human newborns with severe respiratory failure even if no extrapulmonary shunting via ductus or foramen ovale is apparent. Received: 18 March 1997 and revised form 6 September 1997 / Accepted: 7 September 1997     

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).     

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     

Disease-related response to inhaled nitric oxide in newborns with severe hypoxaemic respiratory failure

Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10–80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was significantly reduced in either preterm neonates (51 ± 21 vs 23 ± 17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45 ± 20 vs 20 ± 17, P < .0001), `idiopathic' PPHN (39 ± 14 vs 14 ± 9, P < .0001), and sepsis (55 ± 25 vs 26 ± 20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less significant and sustained (OI = 41 ± 16 vs 28 ± 18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI = 58 ± 25 vs 46 ± 32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age ≥34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants. Received: 24 April 1997 / Accepted in revised form 3 January 1998     

Cardiopulmonary interaction during partial liquid ventilation in surfactant-treated preterm lambs

Gas ventilation following instillation of perfluorochemical (PFC) liquid, partial liquid ventilation (PLV), improves gas exchange and pulmonary mechanics in neonatal animals and humans with severe respiratory distress. The effect of PLV on cardiac contractility, performance, pulmonary blood flow and ductal shunt has not been fully described. To this end, we evaluated these indices of cardiopulmonary function in eight conventionally gas ventilated, surfactant-treated premature lambs (125 days gestation) before and during PLV. Animals were instrumented with central venous and aortic lines. Serial evaluation of arterial blood chemistry/pressure, and pulmonary mechanics was performed; cardiac contractility, performance, pulmonary blood flow and ductal shunts were serially assessed by echocardiography. As compared to conventional gas ventilation, during PLV there was a significant decrease in left ventricular meridian (22.5 ± 6.6 SE vs 8.1 ± 1.4 SE g/cm², P < 0.02) and circumferential wall stress (54.1 ± 16.5 vs 24.4 ± 3.8 SE g/cm², P < 0.04) at end systole. The fall in wall stress at end systole was associated with a significant decrease in left ventricular internal diameter (1.2 ± 0.05 SE vs 1.04 ± 0.045 SE cm; P < 0.01). There were no significant changes in heart rate, systemic arterial and central venous pressures, systemic vascular resistance, left ventricular shortening and ejection fractions during PLV. The decrease in wall stress was associated with a significant decrease in mean airway pressures (15.9 ± 1.1 SE vs 9.9 ± 0.2 SE cmH₂O; P < 0.05) and ostensibly a change in intrathoracic pressures during PLV. There were no significant differences in blood flows (pre vs during PLV; ml/min/kg): pulmonary (226 ± 62 SE vs 293 ± 65 SE), aortic (237 ± 36 SE vs 204 ± 21 SE), and left to right ductal (119 ± 25 SE vs 105.5 ± 26 SE) measured before and during PLV. Conclusion Cardiac output and pulmonary blood flow do not change significantly during PLV and therefore do not appear to contribute to improved gas exchange. This stable cardiac performance occurs at lower wall stress and thereby more advantageous energetic conditions. Received: 18 July 1996 and in revised form: 28 May 1997 / Accepted: 31 May 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.     

Clinical significance of plasma endothelin levels in patients with biliary atresia

Biliary atresia (BA) is the end-result of a destructive inflammatory process that affects intra- and extrahepatic bile ducts, leading to fibrosis and obliteration of the biliary tracts with the development of biliary cirrhosis and portal hypertension (PH). Endothelins (ET) are 21-amino-acid peptides of endothelial origin with potent vasoconstrictor activity that bind to various cells of the liver. Nothing is presently known about plasma ET levels in BA. The aim of this study was to determine the clinical significance of plasma ET levels in patients with BA after hepatic portoenterostomy (Kasai's procedure) and to correlate these with liver function tests (LFT) and PH. We measured plasma concentrations of ET in 19 patients with BA (5 boys and 14 girls; mean age 11.6 ± 5.5 years) after portoenterostomy and 10 age-matched controls. Patients were grouped according to outcome based on LFT: group A consisted of 9 patients with an ‘‘unfavorable outcome” and Group B 10 patients with a “favorable outcome”. The plasma ET levels were measured using a highly sensitive and specific enzyme immunometeric assay (EIA). No patient had ascites or hepatorenal syndrome. Plasma ET levels were significantly higher in patients with BA than in controls (3.42 ± 0.42 vs 1.75 ± 0.39 pg/ml, respectively; P < 0.01) and in patients in group A than in group B. (3.75 ± 0.25 vs 3.06 ± 0.23 pg/ml, respectively; P < 0.01). In group A, plasma ET levels were higher in patients with PH (n = 4) than in those without PH (n = 5) (3.99 ± 0.06 vs 3.64 ± 0.22 pg/ml, respectively; P < 0.05). We conclude that plasma ET levels are high in patients with BA, especially those with severe biliary cirrhosis, and that ET may partially contribute to development of PH in BA. The results of the present study also suggest that plasma ET concentrations may be a useful marker in the follow-up of patients with BA. Accepted: 12 September 1997     

The influence of growth hormone monotherapy and growth hormone in combination with oxandrolone or testosterone on thyroxid hormone parameters and thyrxine binding globulin in patients with Ullrich- Turner syndrome

 Administration of human growth hormone (GH) has yielded conflicting results concerning its role on thyroid function in patients with Ullrich-Turner syndrome. Therefore, we investigated the course of thyroid hormone parameters and thyroxin binding globulin in relation to GH therapy, IGF-I and additional oxandrolone-(Ox) or testosterone (T) treatment in 20 patients with Ullrich-Turner syndrome. During the 1st year the patients received only GH. There was no change in T4, fT4, and TSH levels, T3 increased significantly (P <  0.01) after 6 and 12 months, resulting in a higher T3/T4 ratio. TBG (P < 0.05) and IGF-I (P < 0.01) increased after 6 months and remained elevated at 12 months. A significant positive correlation was found between the change of T4 and TBG after 6 months (r = 0.47, P < 0.05) and after 12 months (r = 0.69, P < 0.005). Thirteen patients were further investigated after addition of an anabolic compound; 7 received Ox (0.0625 mg/kg/day po) and 6 low dose T (5 mg i.m. every 14 days). Chronological age was comparable in these groups (10.7 ±  2.7 vs 10.7  ± 3.6 years). After 6 months of combination therapy with Ox, T4, T3 and TSH decreased. As T4 and T3 showed a parallel decrease the T3/T4 ratio remained elevated. TBG declined after 6 and 12 months (P < 0.05), while IGF-I showed a further increment (P < 0.05). There was no correlation between the changes in T4 and IGF-I, TSH and TBG, respectively. In the T-treated group only IGF-I increased (P < 0.05) to the same extent as in the Ox-treated patients, whereas the thyroid parameters did not change. Conclusion The observed changes in thyroid hormone and TBG levels in the Ox group were not mediated by GH or IGF-I. The Ox-induced TBG decrease might be linked to altered pancreatic functions regulating carbo-hydrate metabolism. Received: 22 April 1996 / Accepted: 1 August 1996     

Evaluation of postoperative pulmonary regurgitation after surgical repair of tetralogy of Fallot: comparison between Doppler echocardiography and MR velocity mapping

Background Pulmonary regurgitation is a common finding in patients after correction of tetralogy of Fallot (TOF). Right ventricular impairment and even ventricular arrhythmia have been ascribed to pulmonary valve insufficiency (PI), which is therefore an important issue in follow-up examinations. Objective To compare PI measured by echocardiography (ECHO) with data provided by cardiac MRI (CMR). Materials and methods We studied 54 selected patients (18 female; median age 14.0 years, range 3.8–53.4 years) after surgical correction of TOF. To quantify pulmonary regurgitant fraction (PRF) by CMR, flow velocity mapping was performed. On Doppler ECHO, length, width and localization of regurgitant flow was measured. The severity of PI was categorized as mild, moderate or severe and compared to the data obtained by CMR. Results On CMR the mean PRF was 29.2 ± 13.4%. Patients with a transannular patch had a significantly higher PRF (39.9 ± 11.6%) than patients with an intact annular ring (23.6 ± 11.4%). Differentiation by Doppler ECHO between the categories mild, moderate and severe PI was confirmed by significant differences in PRF measured by CMR (mild vs. moderate P < 0.04; moderate vs. severe P < 0.014; mild vs. severe P < 0.001). Furthermore, PRF correlated with right ventricular end diastolic volume index (r = 0.45, P < 0.01) and right ventricular end systolic volume index (r = 0.39, P < 0.01). Conclusion Doppler ECHO can estimate the severity of PI after repair of TOF with acceptable results compared to CMR flow measurement. In univariate analysis there is only a weak influence of PRF on right ventricular volume.     

Tachycardia as a potential risk indicator for coronary arterial lesions in Kawasaki disease

Tachycardia is frequently observed in the acute phase of Kawasaki Disease (KD) patients. However, little is known about the association between the tachycardia in the acute phase of KD and the development of coronary arterial lesions (CAL). We examined the association between the mean 24 h heart rate in the acute phase of KD observed using 24 h ambulatory ECG monitoring (24 h-ECG) and the occurrence of CAL in patients. In a study conducted between 1994 and 1997, 26 patients with KD underwent 24 h-ECG within the febrile period and before the 9th day of illness. We compared the mean 24 h heart rate based on 24 h-ECG between patients with and those without CAL. Of 26 patients, 7 had CAL. The groups with and without CAL had similar baseline characteristics. The mean 24 h heart rate in the group with CAL was significantly higher than that in the group without CAL (144 ± 14 vs. 124 ± 22, P = 0.033). On multiple regression analysis, the mean 24 h heart rate was significantly correlated with the development of CAL (P = 0.019). Conclusion Marked tachycardia detected by 24 h-ambulatory ECG monitoring in the acute phase of Kawasaki disease might provide important information on the development of coronary arterial lesions. Received: 18 May 1998 / Accepted in revised form: 23 September 1998     

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     

Total energy expenditure in infants with bronchopulmonary dysplasia is associated with respiratory status

Growth failure is a well-known problem in infants with bronchopulmonary dysplasia (BPD). We studied BPD infants' total daily energy expenditure (Ee), nutritional balance, and growth in relation to their past and current clinical status. Applying the doubly labelled water technique, Ee was measured in nine preterm infants with BPD receiving supplemental oxygen (postnatal age 61 ± 13 days) and nine matched controls (36 ± 21 days) during a 6-day period. Energy and protein balance, past and present respiratory status, and growth were assessed as well. The results show that Ee was higher in the BPD infants compared to controls (73 ± 9 vs 63 ± 8 kcal/kg/day, P < 0.05), but their faecal energy loss was lower (P < 0.01). Weight gain, energy intake, energy cost of growth, protein retention, and physical activity were not different. The respiratory frequency (RR) in the BPD infants was elevated in comparison with controls (P < 0.01). Within the BPD group, RR was positively correlated with energy expenditure (regression equation: Ee [kcal/kg/day] = 26.3 + 0.71*RR [min⁻¹]; r ² = 0.82, P < 0.001), and was the single most significant determinant of Ee. Conclusion Total energy expenditure in BPD infants is elevated and is strongly associated with their respiratory status. These findings could be of practical value for the nutritional management in infants with severe BPD. Received: 17 January 1996 / Accepted: 23 July 1996     

Endothelial dysfunction in adult patients with a history of Kawasaki disease

To assess the existence of endothelial dysfunction and the possibility of the early onset of atherosclerosis in the chronic stage of Kawasaki disease (KD), we examined endothelial function in adult patients late after the onset of KD. We evaluated two age-matched groups: 35 adult KD patients (KD group) (mean age, 27.0 years; mean interval time, 24.1 years), and 36 healthy adults (control group). To assess vascular endothelial function, flow-mediated dilatation (%FMD) of the brachial artery and urinary nitrites and nitrates (NOx) were examined. We also measured adhesion molecules and several coagulation-fibrinolysis markers. In addition, we measured high-sensitive C-reactive protein (hs-CRP) as a chronic inflammatory marker, and brachial-ankle pulse wave velocity (baPWV) as a marker for arterial stiffness. %FMD was significantly reduced in the KD group when compared with that of the control group (KD group, 10.4 ± 2.6%; control group, 14.4 ± 3.2%, p<0.05), particularly in patients with coronary artery lesions. Thrombin-antithrombin III complex values were higher in the KD group, although no significant differences were observed in the other markers for endothelial function. Hs-CRP was significantly elevated only in the patients with coronary aneurysms. Furthermore, in the male KD patients, the baPWV values were significantly higher than those in the control subjects. This study revealed that the adult patients with a history of KD had systemic vascular endothelial dysfunction, and also suggested that a history of KD was possibly one of the risk factors for early onset of atherosclerosis.     

Ureaplasma urealyticum colonization and bronchopulmonary dysplasia: a comparative prospective multicentre study

To determine the role of tracheal colonization at birth with Ureaplasma urealyticum and other pathogenic bacteria with regard to the development of bronchopulmonary dysplasia (BPD), 97 premature infants with very low birth weight (<1500 g) were followed prospectively over 30 days in a multicentre study. Of those infants, 35 were colonized with Ureaplasma urealyticum (group Ia), 22 with other pathogenic bacteria (group Ib) and 40 infants with sterile tracheal aspirates served as controls (group II). Colonization with Ureaplasma urealyticum or with pathogenic bacteria independently increased the risk of developing BPD as compared to the controls (OR 2.55; 95% CI [1.11, 5.87]). Among Ureaplasma urealyticum and bacterial colonized infants, duration of mechanical ventilation and oxygen requirement were significantly longer than among controls (P < 0.05); during the interval of 11 to 35 days of life, every additional day of ventilation significantly increased the risk of BPD (OR 1.22; CI [1.12, 1.32]). The rate of oxygen supplementation, which was similar in both groups during the first 2 weeks of life, was significantly higher among the colonized infants at day 21 (0.38 ± 0.18 and 0.39 ± 0.16 vs 0.31 ± 0.13, P < 0.05) and at day 28 (0.38 ± 0.21 and 0.34 ± 0.15 vs 0.28 ± 0.12, P < 0.05). For infants still ventilated at age of 28 days, Ureaplasma urealyticum and bacterial colonization were associated with a significant higher risk for BPD than for uncolonized controls (OR 5.53; [1.27, 24.02]. Association of Ureaplasma urealyticum and of bacterial colonization and BPD was not weakened after adjustments were made in a multivariate analysis for other significant risk factors. Conclusion Ureaplasma urealyticum colonization is as an important risk factor in the development of bronchopulmonary dysplasia as bacterial colonization even after treatment with surfactant. Received: 23 January 1997 and in revised form: 30 December 1997 / Accepted: 5 January 1998     

Right Ventricular Diastolic Function After Repair of Tetralogy of Fallot

The objective of this study was quantitate diastolic dysfunction in the postoperative phase of tetralogy of Fallot (TOF) and to correlate it with the type of surgical procedure and clinical parameters. Fifty consecutive patients (mean age, 5.0 years; mean weight, 13.5 kg), operated for TOF during the period November 2004 to May 2005, were prospectively studied [infundibular resection, 23; infundibular resection and transannular patch (TAP), 19; right ventricle→pulmonary artery conduit, 8). Detailed echocardiography was done on postoperative days 3 and 9 with a focus on Doppler indices of right ventricular (RV) function, Antegrade late diastolic flow in the right ventricular outflow tract (RVOT) was taken as the marker of restrictive RV physiology. The previous parameters were correlated to the type of surgery and clinical indices of RV dysfunction. There was no mortality. Twenty-four patients showed restrictive RV physiology. This finding correlated with lower values of E/A ratio (0.98 ± 0.17 vs 1.33 ± 0.49, p < 0.002), tricuspid valve E-wave deceleration time (86.9 ± 21.7 vs 151.4 ± 152 msec, p < 0.05), index of myocardial performance (0.15 ± 0.06 vs 0.26 ± 0.09, p < 0.001), isovolumic relaxation time (19.4 ± 17 vs 39±30 msec, p < 0.009), and a higher central venous pressure (15.1 ± 1.5 vs 12.7 ± 1.9, p < 0.001). Restrictive RV physiology correlated with prolonged intensive case unit (ICU) stay (5.1 ± 3.7 vs 2.8 ± 2 days, p < 0.015), longer duration of inotropic support (108.3 ± 56.2 vs 55.5 ± 28.3 hours, p < 0.02), and higher dosage of diuretics. RV diastolic dysfunction is demonstrable by Doppler echocardiography in the first week following surgery for TOF and tends to be worse with TAP. Restrictive physiology demonstrated by RVOT pulse Doppler predicts longer duration of inotropic support, prolonged ICU stay, and higher dosage of diuretics.     

Recovery of the Chronically Hypoxic Young Rabbit Heart Reperfused Following No-Flow Ischemia

The objective of this study was to test whether chronically hypoxic immature hearts exhibit greater tolerance to no-flow ischemia than normoxic hearts. Rabbits (N = 36) were raised from birth to 5 weeks of age in either hypoxic (10% O₂/90% N₂) or normoxic (room air) environment. Isolated, isovolumically beating hearts, with a fluid-filled balloon catheter in the left ventricular chamber, were perfused with a well-oxygenated buffer and studied during baseline [30 minutes; perfusion pressure, 60 mmHg; end diastolic pressure (EDP), 5 mmHg], no-flow ischemia (until onset of contracture or for 30 minutes), and Reperfusion (30 minutes; perfusion pressure, 60 mmHg). Time for onset of contracture (TOC) was defined by an increase in balloon pressure of 5 mmHg. The results were as follows: hypoxic vs normoxic: Hct, 56.4 ± 2.5* vs 36.3 ± 0.4%, (right ventricle/left ventricle) weight (dry) ratio, 0.50 ± 0.04* vs 0.28 ± 0.02. Baseline: developed pressure (ΔP), 96 ± 4 vs 93 ± 5 mmHg; coronary flow, 90 ± 10* vs 62 ± 4 ml/min/g_dry. No-flow ischemia: TOC, 12 ± 1* vs 24 ± 2 minutes. All hypoxic (no normoxic) hearts reached peak contracture. Reperfusion: Just after onset of contracture, ΔP, 80 ± 3* vs 67 ± 4 mmHg; EDP, 5 ± 1* vs 13 ± 2 mmHg; after 30 minutes of no-flow ischemia, ΔP, 58 ± 5 vs 46 ± 4 mmHg; EDP, 13 ± 1* vs 24 ± 3 mmHg; lactate release (LR), 0.15 ± 0.01 vs 0.17 ± 0.01 mmol/g_dry, creatine kinase release (CKR), 46 ± 8* vs 242 ± 28 U/g_dry. For hypoxic hearts reperfused after onset of contracture, LR was 0.11 ± 0.03 mmol/g_dry, comparable to that following 30 minutes of no-flow ischemia (*p < 0.05). Rabbit hearts subjected to hypoxia from birth developed ischemic contracture earlier and reached peak contracture, showed no significant increase in LR after onset of contracture, exhibited better recovery of EDP, and had markedly reduced CKR compared to normoxic controls.     

A Prospective Analysis of the Incidence and Risk Factors Associated with Junctional Ectopic Tachycardia Following Surgery for Congenital Heart Disease

This study was designed to evaluate the incidence and risk factors associated with the occurrence of junctional ectopic tachycardia (JET) in patients after congenital heart surgery. We prospectively analyzed cardiac rhythm status in 336 consecutive patients undergoing surgery for congenital heart disease at our institution during a 1-year period. The incidence of JET was 8% (27/336). Repairs with the highest incidence of JET were arterial switch operation (3/13, 23%), atrioventricular (AV) canal repair (4/19, 21%), and Norwood repair (2/10, 20%). Compared to patients with no arrhythmias, patients with JET were more likely to be younger (2.75 ± 2.44 vs 5.38 ± 7.25 years, p < 0.01), have had longer cardiopulmonary bypass times (126 ± 50 vs 85 ± 73, p < 0.01), and have a higher inotrope score (6.26 ± 7.55 vs 2.41 ± 8.11, p < 0.01). By multivariate analysis, ischemic time was the only factor associated with JET [odds ratio, 1.01 (confidence interval, 1.005–1.02); p = 0.0014). The presence of JET did not correlate with electrolyte abnormalities. JET is not necessarily related to surgery near the His bundle or hypomagnesemia. Longer ischemic time is the best predictor of JET. Patients undergoing arterial switch operation, AV canal repair, and Norwood repair are at highest risk of postoperative JET and should be considered for prophylactic therapy.