Efficacy of corticosteroids in prevention of acute kidney injury in neonates undergoing cardiac surgery-A randomized controlled trial.

BACKGROUND: Heart surgery requiring cardiopulmonary bypass (CPB) causes an inflammatory response which may further induce acute kidney injury (AKI). In the present randomized controlled study we evaluated whether corticosteroids can prevent CPB related AKI in neonates undergoing heart surgery. METHODS: Forty neonates were randomized to receive 2 mg/kg methylprednisolone followed by hydrocortisone infusion 0.2 mg/kg/h perioperatively with tapering doses for 5 days, or placebo administered in a similar fashion. The primary outcome was the inflammatory response (plasma concentrations of interleukins 6 and 10). The correspondence of the interleukin concentrations with AKI was analysed as secondary outcome. In addition, plasma and urine neutrophil gelatinase-associated lipocalin (NGAL), plasma cystatin C, and urine kidney injury molecule-1 (KIM-1) levels were measured. RESULTS: Six patients (15%) developed post-operative AKI. No significant difference in the AKI occurrence between the treatment (n = 2) and the placebo (n = 4) groups could be found (risk ratio 2.00, 95% confidence interval 0.41-9.71; P = .661) despite significant reduction in inflammatory response in the treatment group. One patient in the treatment group and two patients in the placebo group required acute peritoneal dialysis. Plasma creatinine and cystatin C or urine NGAL and KIM-1 concentrations did not differ between the treatment and the placebo group. CONCLUSIONS: Significantly reduced inflammatory reaction induced by corticosteroid treatment in neonates undergoing cardiac surgery did not reduce the incidence of AKI defined by KDIGO classification or decrease the rise of AKI biomarkers.

High-dose methylprednisolone and endothelial glycocalyx in paediatric heart surgery.

BACKGROUND: Corticosteroids are used in paediatric heart surgery to attenuate systemic inflammatory response. Glycocalyx regulates vascular permeability, shear stress and cell adhesion on the endothelium. Syndecan-1 serves as a biomarker of glycocalyx degradation. Hydrocortisone decreased endothelial glycocalyx degradation in an experimental model. Our hypothesis was that high-dose methylprednisolone decreases glycocalyx degradation as measured by plasma sydecan-1 concentration in children undergoing cardiac surgery. METHODS: Two double-blinded, randomized, placebo-controlled trials were conducted. In the first trial ('neonatal trial'), 40 neonates undergoing open heart surgery received either 30 mg/kg intravenous methylprednisolone (n = 20) or placebo (n = 20). In the second trial ('VSD trial'), 45 infants and very young children, undergoing ventricular or atrioventricular septal defect correction received one of the following: 30 mg/kg of methylprednisolone intravenously after anaesthesia induction (n = 15), 30 mg/kg methylprednisolone in the cardiopulmonary bypass prime solution (n = 15) or placebo (n = 15). Plasma syndecan-1 concentrations were measured. Results were expressed both as absolute concentrations and in relative concentrations as multiples of the baseline values of syndecan-1. RESULTS: There were no statistically significant differences between the neonate trial groups for absolute syndecan-1 concentrations. However, operative administration of methylprednisolone to neonates significantly reduced the relative increases of syndecan-1 at weaning from cardiopulmonary bypass (P = 0.008) and at 6 h post-operatively (P = 0.018). There were no statistically significant differences in absolute or relative increases of syndecan-1 between the VSD trial study groups. CONCLUSION: High-dose methylprednisolone reduces shedding of glycocalyx in neonates after complex cardiac surgery but not in older infants after repair of VSD/AVSD with shorter ischaemia times.

Intraosseous access in neonates and infants: risk of severe complications - a case report.

Gaining vascular access in a neonate during cardiopulmonary resuscitation is crucial and challenging. Intraosseous (IO) access can offer a fast and reliable method for achieving emergency access for fluids and drugs when venous access fails in a critically ill child. IO access can however result in rare, but serious adverse events including compartment syndrome and amputation. We describe a case resulting in leg amputation due to IO infusion in a neonate after resuscitation and therapeutic hypothermia. We compared 10 tibia X-rays in three age groups. The mean medullary diameter of the proximal tibia at the recommended site for IO access was 7 mm in neonate, 10 mm in 1- to 12-month-old infants, and 12 mm in 3- to 4-year-old children. This provides a narrow margin of safety for the correct positioning and the avoidance of dislodgement of the IO needle. The correct position of the IO needle should be confirmed by bone marrow aspiration and fluid bolus. Unnecessary touching of the IO needle after fixing it in place should be avoided by inserting a luer-lock catheter with a three-way stop-cock for IO drug and fluid administration. Regular observation of the circulation and possible swelling of the leg should be performed. The IO administration of inotropic infusions should also be avoided after the initial resuscitation phase. When treating with therapeutic hypothermia, it may be wise to remove the IO needle much earlier than the currently recommended 24 h because of the problems in peripheral circulation and its monitoring.

Drowning in children: Utstein style reporting and outcome.

BACKGROUND: We report the incidence and mortality of paediatric drowning incidents according to 'Utstein Style for Drowning' guidelines. METHODS: Retrospective study including all the drowned children under 16 years of age who were hospitalised or died with or without attempted cardiopulmonary resuscitation (CPR) between 1997 and 2007 in the province of Uusimaa, Finland. Survival rates provided at hospital discharge and after 1-year follow-up period are reported. RESULTS: A total of 58 drowned children were either admitted to the paediatric intensive care unit or died during the study period. The median (interquartile range) age was 5.9 (3.1, 7.8) years. The annual incidence of drowning was 1.9/100,000 and was highest, 2.8/100,000, in children aged between 1 and 4 years. The annual mortality rate was 0.9/100,000. Of all the 58 patients, 14 (24%) died at the scene, 22 (38.1%) before the hospital discharge, and 26 (45%) within the 1 year. The number of non-fatal drownings was 1.2-fold that of fatal drownings. The survival rate of the 26 patients for whom CPR was initiated by emergency medical service (EMS) personnel was 42% at hospital discharge, with the 1-year survival rate being 27%. CONCLUSIONS: The incidence of drowning in children and the survival rate of those children in whom CPR was initiated by EMS personnel was in line with the previously reported. However, the overall mortality rate in drowned children was higher than estimated in previous studies.

The effect of tepid amino acid-enriched induction cardioplegia on the outcome of infants undergoing cardiac surgery.

BACKGROUND: Despite promising experimental results, no information has been published on the clinical effects of amino acid-enriched induction cardioplegic solution on outcome in children undergoing cardiac surgery. METHODS: This is a retrospective study of 185 consecutive patients younger than 12 months with one of the following defects undergoing open heart surgery: atrioventricular septal defect, transposition of the great arteries, tetralogy of Fallot or ventricular septal defect. Patients were divided into two groups according to the following myocardial protection approaches: tepid substrate-enriched induction cardioplegia followed by cold blood cardioplegia (n=113) or only cold blood induction cardioplegia (n=72). Patient allocation was determined by the anesthesiologist in charge of cardiopulmonary bypass (CPB). The primary outcome measure was postoperative myocardial injury assessed by troponin T level and inotrope score. RESULTS: Demographic data were similar for both groups. Cardioplegic induction had no overall effect for inotrope score (16.3 ± 9.2 vs.17.9 ± 10.0, p=0.276) or lactate release (1.8 ± 1.3 vs. 1.6 ± 0.8, p=0.110) on arrival to the paediatric intensive care unit. On the first postoperative day, there were no significant differences between the cardioplegia groups for inotrope score (13.7 ± 8.7 vs.14.3 ± 9.1, p=0.657), troponin T (2.4 ± 1.6 vs. 2.8 ± 2.7 µg/L, p=0.267), lactate (1.5 ± 2.0 vs. 1.5 ± 0.8, p=0.972), or any of the other clinical outcome measures. CONCLUSIONS: Compared to cold cardioplegia alone, the administration of tepid induction cardioplegia had no effect on the clinical outcome of infants who underwent cardiac surgery.

Outcome of drowned hypothermic children with cardiac arrest treated with cardiopulmonary bypass.

BACKGROUND: There is a lack of data on the outcome of cardiopulmonary bypass (CPB) rewarming of hypothermic children with cardiac arrest following drowning. AIM OF THE STUDY: To retrospectively analyze single-center outcome of drowning victims treated with CPB. MATERIALS AND METHODS: This retrospective study included all hypothermic drowning victims admitted to the Hospital for Children and Adolescents with attempted resuscitation on CPB between 1994 and 2008 inclusive. Median sternotomy and cannulation of the ascending aorta and the right atrium for CPB were performed on all victims. RESULTS: Nine hypothermic drowning victims, comprising five boys and four girls, with a median age of 3.8 years (range, 1.5-10 years). The median submersion time was 38 min (range, 5-75 min) and the median water temperature was 6.5 °C (range, 0.2-16.5 °C). The median core temperature was 21.9 °C (range 17.7-32.8 °C) at arrival to the hospital. All nine children were able to be weaned from CPB. Only one child, with mild to moderate neurological deficit, became a long-term survivor. She was slowly rewarmed up to 33 °C with CPB and kept in mild hypothermia for 48 h. CONCLUSIONS: Large numbers of submerged children can be primarily resuscitated with CPB. Unfortunately, many of them will decease from severe hypoxic brain injury. Slow rewarming with CPB may improve the likelihood of a better neurological outcome.

Electron cyclotron resonance ion sources with arc-shaped coils.

The minimum-B magnetic field structure of electron cyclotron resonance ion sources (ECRIS) has conventionally been formed with a combination of solenoids and a hexapole magnet. However, minimum-B structure can also be formed with arc-shaped coils. Recently it was shown that multiply charged heavy-ions can be produced with an ECRIS based on such a structure. In the future, the ARC-ECRIS magnetic field structure can be an interesting option for radioactive ion-beam sources and charge-breeders as well as for high performance ECRIS allowing for 100 GHz plasma heating. This paper presents some design aspects of the ARC-ECRIS.

Ion beam development for the needs of the JYFL nuclear physics programme.

The increased requirements towards the use of higher ion beam intensities motivated us to initiate the project to improve the overall transmission of the K130 cyclotron facility. With the facility the transport efficiency decreases rapidly as a function of total beam intensity extracted from the JYFL ECR ion sources. According to statistics, the total transmission efficiency is of the order of 10% for low beam intensities (I(total)< or =0.7 mA) and only about 2% for high beam intensities (I(total)>1.5 mA). Requirements towards the use of new metal ion beams for the nuclear physics experiments have also increased. The miniature oven used for the production of metal ion beams at the JYFL is not able to reach the temperature needed for the requested metal ion beams. In order to fulfill these requirements intensive development work has been performed. An inductively and a resistively heated oven has successfully been developed and both are capable of reaching temperatures of about 2000 degrees C. In addition, sputtering technique has been tested. GEANT4 simulations have been started in order to better understand the processes involved with the bremsstrahlung, which gives an extra heat load to cryostat in the case of superconducting ECR ion source. Parallel with this work, a new advanced ECR heating simulation program has been developed. In this article we present the latest results of the above-mentioned projects.

A status report of the multipurpose superconducting electron cyclotron resonance ion source.

Intense heavy ion beam production with electron cyclotron resonance (ECR) ion sources is a common requirement for many of the accelerators under construction in Europe and elsewhere. An average increase of about one order of magnitude per decade in the performance of ECR ion sources was obtained up to now since the time of pioneering experiment of R. Geller at CEA, Grenoble, and this trend is not deemed to get the saturation at least in the next decade, according to the increased availability of powerful magnets and microwave generators. Electron density above 10(13) cm(-3) and very high current of multiply charged ions are expected with the use of 28 GHz microwave heating and of an adequate plasma trap, with a B-minimum shape, according to the high B mode concept [S. Gammino and G. Ciavola, Plasma Sources Sci. Technol. 5, 19 (1996)]. The MS-ECRIS ion source has been designed following this concept and its construction is underway at GSI, Darmstadt. The project is the result of the cooperation of nine European institutions with the partial funding of EU through the sixth Framework Programme. The contribution of different institutions has permitted to build in 2006-2007 each component at high level of expertise. The description of the major components will be given in the following with a view on the planning of the assembly and commissioning phase to be carried out in fall 2007. An outline of the experiments to be done with the MS-ECRIS source in the next two years will be presented.

The performance of Bispectral Index in children during equi-MAC halothane vs. sevoflurane anaesthesia.

BACKGROUND AND OBJECTIVE: The reliability of the Bispectral Index for evaluating and monitoring the depth of general anaesthesia in children is not as great as for that in adults. Therefore we analysed Bispectral Index performance in children by comparing changes in Bispectral Index values during a standardized and equipotent anaesthetic regimen using either halothane or sevoflurane for the induction and maintenance of general anaesthesia. Special interest was focussed on excitation during induction, and whether it was associated with simultaneous changes in Bispectral Index scores. METHODS: Twenty children (3-15 yr, ASA I-II) scheduled for general surgery were randomly allocated to either halothane (10 patients) or sevoflurane group (10 patients). Anaesthesia was induced by 3% halothane or 7% sevoflurane, either agent administered with 50% N2O in oxygen for 5 min, the period from the beginning of induction until intubation. Thereafter, anaesthesia was maintained by the respective volatile agent at 1 MAC (minimum alveolar concentration; in addition to 70% N2O in oxygen) and supplemented with remifentanil infusion adjusted to maintain the heart rate and mean arterial pressure to within 20% of the baseline values. Excitation at induction was defined as involuntary muscular movements. RESULTS: Sevoflurane induction produced a more rapid depression in Bispectral Index than halothane, the mean difference being greatest (47 Bispectral Index score) at 105 s. Excitation occurred in three patients during sevoflurane induction, which coincided with increases in Bispectral Index values in two of the three patients. During the maintenance phase at 1 MAC, the Bispectral Index (mean +/- SD) was 57+/-7 for halothane and 47+/-9 for sevoflurane (P < 0.05). The remifentanil doses did not differ between both groups. CONCLUSION: In children, halothane anaesthesia was associated with higher Bispectral Index values than sevoflurane when administered at 1 MAC. Large individual variation in Bispectral Index occurred within both groups. Due to these limitations, one should be cautious when interpreting paediatric Bispectral Index data.

Serum TRACP 5b and ICTP as markers of bone metastases in breast cancer.

BACKGROUND: The purpose of this cross-sectional study was to evaluate the value of serum tartrate-resistant acid phosphatase 5b (TRACP 5b) and carboxyterminal telopeptide of type I collagen (ICTP) separately and in combination as markers of bone metastases compared to total alkaline phosphatase (tALP) in breast cancer. MATERIALS AND METHODS: Two groups of patients were studied, one with verfied bone metastases (N=46) and one without bone metastases (N=141). Bone marker levels were correlated with the presence or absence of bone metastases. RESULTS: Serum TRACP 5b concentrations exhibited the largest area under the receiver-operating characteristics (ROC) curve (AUC=0.845), followed by ICTP (0.818) and tALP (0.814) when all patients were included in the analysis. With the combination of TRACP 5b and ICTP, the AUC increased to 0.881. In multivariate regression analysis, all three markers were significant predictors of bone metastases. CONCLUSION: Serum TRACP 5b, ICTP and tALP exhibited equal performances in the detection of bone metastases. The combination of TRACP with ICTP did not significantly improve the detection of bone metastases over tALP.

Secretion of the Hormoconis resinae glucoamylase P enzyme from Trichoderma reesei directed by the natural and the cbh1 gene secretion signal.

Secretion of the Hormoconis resinae glucoamylase P (GAMP) enzyme from Trichoderma reesei using either the natural N-terminal extension of the premature glucoamylase P or the cellobiohydrolase I (CBHI) signal peptide was examined. The expression conditions for the heterologous glucoamylase P (gamP) gene in T. reesei were standardized by targeting one copy of a plasmid fragment, containing the gamP gene, to the cbh1 locus of the host. The results showed that the transient N-terminal extension of the premature GAMP acts as an efficient secretion signal in T. reesei and leads to a higher yield of extracellular glucoamylase activity than does the signal peptide of CBHI.

Immunoaffinity Chromatographic Purification of Cellobiohydrolase II Mutants from Recombinant Trichoderma reesei Strains Devoid of Major Endoglucanase Genes

Efficient purification of Trichoderma reesei cellobiohydrolase II (CBHII) requires the use of affinity chromatography based on a substrate analogue. Due to altered substrate binding, the purification of many active-site mutants of CBHII from the complex fungal culture media represents a considerable challenge. Here we describe a combination of two approaches to facilitate the purification: the first is based on the construction of novel engineered T. reesei strains devoid of the major contaminating endoglucanases, and the second uses immunoaffinity chromatography as the final purification step. Two different procedures for the preparation of the antibody matrix were tested. Crosslinking of the monoclonal antibody to Protein G matrix instead of the conventional immobilization via cyanogen bromide increased the binding efficiency. Three different active-site mutants of CBHII bound to the immunoaffinity column in neutral pH and were eluted in pH 2.7. The purity of the CBHII mutant preparations was tested using small chromophoric substrates and hydroxyethyl cellulose, which are hydrolyzed by many other cellulases but not by CBHII. The immunoaffinity column purified the CBHII mutants over 800-fold in a single step and resulted in homogeneous protein preparations free of proteolytically cleaved forms of CBHII. The use of the double replacement T. reesei production strains, especially the one lacking the genes coding for both the endogeneous CBHII and the endoglucanase II (EGII), helped to reduce the total endoglucanase activity in the preparations.

On the safety of Trichoderma reesei.

Trichoderma reesei has a long history of safe use in industrial-scale enzyme production. Applications of cellulases and xylanases produced by this fungus are found in food, animal feed, pharmaceutical, textile and pulp and paper industries. T. reesei is non-pathogenic for man and it has been shown not to produce fungal toxins or antibiotics under conditions used for enzyme production. During recent years genetic engineering techniques have also been used to improve the industrial production strains of T. reesei and, in addition, considerable experience of safe use of recombinant T. reesei strains in industrial scale has accumulated. Thus, T. reesei can be generally considered not only a safe production organism of its natural enzymes but also a safe host for other harmless gene products.

X-ray photographic method for determination of stable iodine in tissues.

A new x-ray photographic technique for imaging of small concentrations of iodine in tissues is presented. The method is based on the use of two x-ray beams of slightly different energies, which are obtained from the same primary source by appropriate use of critical absorbers. The beam energies are chosen so that the more energetic one is high enough to excite K x rays of the element under study while the less energetic beam is just below the required excitation energy. Two x-ray pictures are taken using the beams consecutively; thereafter, a difference picture is made by subtracting photographically the lower energy beam picture from that of higher energy. The difference picture then displays the distribution of the element to be imaged. This method is sensitive to iodine concentrations less than 100 microgram/mm2.

Paediatric out-of-hospital cardiac arrests--epidemiology and outcome.

OBJECTIVE: To determine the epidemiology and aetiology of out-of-hospital paediatric cardiac arrest and the outcome of resuscitation and to apply the Utstein template for the paediatric cardiac arrest population. DESIGN: Retrospective cohort study. SETTING: A middle-sized urban city (population 516,000) served by a single emergency medical services (EMS) system. PATIENTS: 79 consecutive paediatric (age under 16 years) prehospital cardiac arrest patients between January 1, 1985 and December 31, 1994. No patient was excluded. INTERVENTION: Advanced paediatric life support according to the recommendations of American Heart Association. MAIN OUTCOME MEASURES: Survival from cardiac arrest to discharge and factors associated with favourable outcome defined as alive 1 year after discharge with Bloom category I or II. RESULTS: 79 patients had cardiac arrest. The incidence of paediatric out-of-hospital cardiac arrest and sudden unexpected out-of-hospital death was 9.8 and 8.9/100,000/inhabitants aged under 16, respectively. The mean age was 2.9 years, 72.2% were under 18 months. SIDS was the leading cause of cardiac arrest followed by trauma, airway related cardiac arrest and (near)drowning. Fifty-two patients were considered for resuscitation in whom asystole was the most common initial rhythm (78.9%) followed by pulseless electrical activity (13.5%) and ventricular fibrillation (3.8%). Resuscitation was attempted in 34 patients. The overall survival rate was 9.6%, for attempted resuscitation 14.7%, for attempted resuscitation when cardiac arrest was witnessed 25.0% and for attempted resuscitation with witnessed arrest of cardiac origin 0%. Favourable outcome was registered in four of five survivors. Factors associated with favourable outcome were collapse in a public place, the near-drowning aetiology of arrest, bystander initiated CPR and short duration of resuscitation. Multivariate regression analysis showed no factor related to favourable outcome, but MICU time interval < 10 min was related with survival. Due to the retrospective nature of this study all core times could not be obtained. In spite of this, the Utstein template was applicable also in our paediatric cardiac arrest population. CONCLUSIONS: Survival from paediatric cardiac arrest has remained low. The overall survival rate was 9.6%, survival after attempted resuscitation 14.7% and 0% when resuscitation was attempted in witnessed arrest of cardiac origin. Asystole was the most common initial rhythm and the four leading causes for cardiac arrest were SIDS, trauma, airway related arrest and (near)drowning. The Utstein template adopted for adult out-of-hospital cardiac arrests was was found applicable also in paediatric cardiac arrests.