Central Diabetes Insipidus in a Preterm Neonate Unresponsive to Intranasal Desmopressin.

Central or neurogenic diabetes insipidus (DI) is uncommon in the pediatric age group and rarely occurs in neonates. It should be suspected in any neonate presenting with excessive urine output and hypernatremia that persists despite increased fluid administration. Diabetes insipidus may be secondary to asphyxia, intraventricular hemorrhage, infection, and structural abnormalities or may be idiopathic or genetic. Diagnosis includes a careful history, laboratory testing, and magnetic resonance imaging. Management of neonatal DI involves a careful balance between fluid intake and pharmacologic treatment. In this article we report a case of an extremely low birth weight infant presenting with central DI possibly caused by abnormality of the pituitary gland. Persistent hypernatremia was the initial presentation. Increased fluids were given initially but were only partially helpful. Eventually subcutaneous desmopressin (DDAVP) was required. The infant was unresponsive to intranasal DDAVP and required subcutaneous DDAVP upon discharge.

Sensitivity analysis of a strongly-coupled human-based electromechanical cardiac model: Effect of mechanical parameters on physiologically relevant biomarkers.

The human heart beats as a result of multiscale nonlinear dynamics coupling subcellular to whole organ processes, achieving electrophysiologically-driven mechanical contraction. Computational cardiac modelling and simulation have achieved a great degree of maturity, both in terms of mathematical models of underlying biophysical processes and the development of simulation software. In this study, we present the detailed description of a human-based physiologically-based, and fully-coupled ventricular electromechanical modelling and simulation framework, and a sensitivity analysis focused on its mechanical properties. The biophysical detail of the model, from ionic to whole-organ, is crucial to enable future simulations of disease and drug action. Key novelties include the coupling of state-of-the-art human-based electrophysiology membrane kinetics, excitation-contraction and active contraction models, and the incorporation of a pre-stress model to allow for pre-stressing and pre-loading the ventricles in a dynamical regime. Through high performance computing simulations, we demonstrate that 50% to 200% - 1000% variations in key parameters result in changes in clinically-relevant mechanical biomarkers ranging from diseased to healthy values in clinical studies. Furthermore mechanical biomarkers are primarily affected by only one or two parameters. Specifically, ejection fraction is dominated by the scaling parameter of the active tension model and its scaling parameter in the normal direction ( k ort 2 ); the end systolic pressure is dominated by the pressure at which the ejection phase is triggered ( P ej ) and the compliance of the Windkessel fluid model ( C ); and the longitudinal fractional shortening is dominated by the fibre angle ( ϕ ) and k ort 2 . The wall thickening does not seem to be clearly dominated by any of the considered input parameters. In summary, this study presents in detail the description and implementation of a human-based coupled electromechanical modelling and simulation framework, and a high performance computing study on the sensitivity of mechanical biomarkers to key model parameters. The tools and knowledge generated enable future investigations into disease and drug action on human ventricles.

Error Bounds for Discontinuous Finite Volume Discretisations of Brinkman Optimal Control Problems.

We introduce a discontinuous finite volume method for the approximation of distributed optimal control problems governed by the Brinkman equations, where a force field is sought such that it produces a desired velocity profile. The discretisation of state and co-state variables follows a lowest-order scheme, whereas three different approaches are used for the control representation: a variational discretisation, and approximation through piecewise constant and piecewise linear elements. We employ the optimise-then-discretise approach, resulting in a non-symmetric discrete formulation. A priori error estimates for velocity, pressure, and control in natural norms are derived, and a set of numerical examples is presented to illustrate the performance of the method and to confirm the predicted accuracy of the generated approximations under various scenarios.

Emissions from corrosion protection systems of offshore wind farms: Evaluation of the potential impact on the marine environment.

Offshore wind energy is a fast growing sector of renewable energies worldwide. This will change the marine environment and thus, a wide range of environmental impacts of offshore wind farms are subject of current research. Here we present an overview about chemical emissions from corrosion protection systems, discuss their relevance and potential impact to the marine environment, and suggest strategies to reduce their emissions. Corrosion is a general problem for offshore infrastructures and corrosion protection systems are necessary to maintain the structural integrity. These systems are often in direct contact with seawater and have different potentials for emissions, e.g. galvanic anodes emitting substantial amounts of metals. Organic coatings may release organic substances due to weathering and/or leaching. Current assumptions suggesting a low environmental impact, but monitoring data is not sufficient to assess the environmental impact of this new source.

Nonlinear diffusion and thermo-electric coupling in a two-variable model of cardiac action potential.

This work reports the results of the theoretical investigation of nonlinear dynamics and spiral wave breakup in a generalized two-variable model of cardiac action potential accounting for thermo-electric coupling and diffusion nonlinearities. As customary in excitable media, the common Q10 and Moore factors are used to describe thermo-electric feedback in a 10° range. Motivated by the porous nature of the cardiac tissue, in this study we also propose a nonlinear Fickian flux formulated by Taylor expanding the voltage dependent diffusion coefficient up to quadratic terms. A fine tuning of the diffusive parameters is performed a priori to match the conduction velocity of the equivalent cable model. The resulting combined effects are then studied by numerically simulating different stimulation protocols on a one-dimensional cable. Model features are compared in terms of action potential morphology, restitution curves, frequency spectra, and spatio-temporal phase differences. Two-dimensional long-run simulations are finally performed to characterize spiral breakup during sustained fibrillation at different thermal states. Temperature and nonlinear diffusion effects are found to impact the repolarization phase of the action potential wave with non-monotone patterns and to increase the propensity of arrhythmogenesis.

Assessment of WINROP algorithm as screening tool for preterm infants in Manitoba to detect retinopathy of prematurity.

OBJECTIVE: Developing less invasive methods for early detection of retinopathy of prematurity (ROP) is vital to minimizing blindness in premature infants. Lofqvist and colleagues developed a computer-based ROP risk algorithm (WINROP) (https://winrop.com), which detects downtrends in postnatal weight gain that correlate with the development of sight-threatening ROP. The aim of this study is to investigate the sensitivity and specificity of the WINROP algorithm to detect vision-threatening ROP. METHODS: This is a retrospective chart review study between January 2008 and December 2013. This study was conducted in the neonatal intensive care unit in Children's Hospital at Health Sciences Centre, Winnipeg, Manitoba, Canada. The study included preterm infants, less than 32 weeks' gestation, who were admitted to the hospital during the study period. The included 215 infants were eligible for ROP screening and had sufficient data to be entered into the WINROP algorithm. Infants were screened by a paediatric ophthalmologist for retinopathy of prematurity. The body weight of infants was measured weekly and entered into the WINROP algorithm; the sensitivity and the specificity of the WINROP algorithm were assessed. RESULTS: The mean gestational age was 28.6 ± 1.8 weeks. The mean body weight was 1244 ± 294 g. The sensitivity of the WINROP algorithm to detect vision-threatening retinopathy of prematurity in our cohort was 90% (P=0.021) with a specificity of 60% (P=0.002). CONCLUSION: The WINROP algorithm lacks sufficient sensitivity to be used clinically in our population. The algorithm needs to be reassessed in contemporary populations.

Radiographic confirmation of feeding tube placement: a diagnostic tool identifying gastrointestinal anomalies.

Feeding tubes are commonly used in neonatal intensive care units, and their abnormal position seen on radiographs may indicate underlying serious problems. We recently cared for two infants who presented with clinical deterioration. An abnormally placed feeding tube seen on the chest radiograph revealed underlying serious conditions. The first case was an infant 29 weeks of age who presented with right-sided pneumothorax after birth. By history and a right-side-displaced orogastric (OG) tube, iatrogenic esophageal perforation was diagnosed. The second case was a 16-day-old infant who presented with recurrent vomiting. An OG tube extending into a cystic mass at the right cardiophrenic angle resulted in diagnosis of a herniated stomach with organoaxial-type volvulus, which required surgical repair. Both cases recovered uneventfully. As illustrated in these two rare cases, feeding tube position is not only important for feeding practice, but it also has diagnostic implications in newborn infants.

Post transfusion lung injury in the neonatal population.

OBJECTIVE: The objective of this study was to examine the changes in level of respiratory support following transfusion in neonates who require intermediate or intensive care. STUDY DESIGN: Data on respiratory support were collected retrospectively from the medical record before, during and after transfusion. Neonatal post transfusion lung injury (NPTLI) was defined as an increase in the highest mean airway pressure (MAP) of ≥2 cm H(2)O or FiO(2) >0.15 in the 6-h after transfusion that persisted from 6 to 18 h post transfusion. RESULT: A total of 373 (330 packed red blood cell) transfusions were given to 108 infants. NPTLI occurred following 31 (8.3%) transfusions in 23 patients. During the first 6 h after transfusion, FiO2 or MAP was increased in 47 transfusions (12.6%) and the changes persisted in 31 transfusions (7.8%). Infants who developed NPTLI were less mature (27.1±0.7 vs 31.0±0.5 weeks; P=0.005) and of lower birth weight (1001±110 vs1692±104 g; P=0.001). Infants who developed NPTLI were more likely to develop necrotizing enterocolitis (6/24 vs 4/85; P=0.002) and die within 24 h of transfusion (5/22 vs 3/85; P=0.003). CONCLUSION: In neonates receiving intensive or intermediate care, blood transfusion was associated with need for increased respiratory support in a significant number of cases. Development of NPTLI was associated with poorer outcomes.

An active strain electromechanical model for cardiac tissue.

We propose a finite element approximation of a system of partial differential equations describing the coupling between the propagation of electrical potential and large deformations of the cardiac tissue. The underlying mathematical model is based on the active strain assumption, in which it is assumed that there is a multiplicative decomposition of the deformation tensor into a passive and active part holds, the latter carrying the information of the electrical potential propagation and anisotropy of the cardiac tissue into the equations of either incompressible or compressible nonlinear elasticity, governing the mechanical response of the biological material. In addition, by changing from a Eulerian to a Lagrangian configuration, the bidomain or monodomain equations modeling the evolution of the electrical propagation exhibit a nonlinear diffusion term. Piecewise quadratic finite elements are employed to approximate the displacements field, whereas for pressure, electrical potentials and ionic variables are approximated by piecewise linear elements. Various numerical tests performed with a parallel finite element code illustrate that the proposed model can capture some important features of the electromechanical coupling and show that our numerical scheme is efficient and accurate.

New variable porosity flow diverter (VPOD) stent design for treatment of cerebrovascular aneurysms.

Using flow diverting Stents for intracranial aneurysm repair has been an area of recent active research. While current commercial flow diverting stents rely on a dense mesh of braided coils for flow diversion, our group has been developing a method to selectively occlude the aneurysm neck, without endangering nearby perforator vessels. In this paper, we present a new method of fabricating the low porosity patch, a key element of such asymmetric vascular stents (AVS).

Cytokine gene polymorphisms in preterm infants with necrotising enterocolitis: genetic association study.

BACKGROUND: The inflammatory cytokine cascade is implicated in the pathogenesis of necrotising enterocolitis (NEC). Genetic association studies of cytokine polymorphisms may help to detect molecular mechanisms that are causally related to the disease process. AIM: To examine associations between the common genetic variants in candidate inflammatory cytokine genes and NEC in preterm infants. METHODS: Multi-centre case-control and genetic association study. DNA samples were collected from 50 preterm infants with NEC and 50 controls matched for gestational age and ethnic group recruited to a multi-centre case-control study. Ten candidate single-nucleotide polymorphisms in cytokines previously associated with infectious or inflammatory diseases were genotyped. The findings were included in random-effects meta-analyses with data from previous genetic association studies. RESULTS: All allele distributions were in Hardy-Weinberg equilibrium. None of the studied cytokine polymorphisms was significantly associated with NEC. Four previous genetic association studies of cytokine polymorphisms and NEC in preterm infants were found. Meta-analyses were possible for several single-nucleotide polymorphisms. These increased the precision of the estimates of effect size but did not reveal any significant associations. CONCLUSIONS: The available data are not consistent with more than modest associations between these candidate cytokine variant alleles and NEC in preterm infants. Data from future association studies of these polymorphisms may be added to the meta-analyses to obtain more precise estimates of effects sizes.

IL-10, IL-6 and CD14 polymorphisms and sepsis outcome in ventilated very low birth weight infants.

BACKGROUND: Genetic variation in the innate immune system of the host may play a role in determining the risk of developing infection, as well as outcome from infection. METHODS: Infectious complications were retrospectively determined in 293 (233 African-American (AA), 57 Caucasian and 3 Hispanic) mechanically ventilated very low birth weight (VLBW) infants (<1500 grams at birth) who were genotyped for the IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T single nucleotide polymorphisms (SNPs). RESULTS: The IL-6 -174C allele was associated with an increased incidence of late blood stream infection (BSI) in AA but not Caucasian infants. In AA infants with the C allele the incidence of late BSI was 20/29 (69%) compared to 94/204 (46%) in homozygous GG infants (RR 2.6, 95% CI: 1.1-6.0, p = 0.021). The IL-10 -1082A allele was associated with an increased incidence of late BSI. One or more episodes of late BSI developed in 14 (35%) of 40 infants with the GG genotype, 71 (49%) of 145 infants with the GA genotype and 63 (58%) of 108 infants with the AA genotype (p = 0.036). Infants with the A allele (AA or GA genotypes) had an incidence of late BSI that was 134/253 (53%) compared to 14/40 (35%) in homozygous GG infants (RR 2.1, 95% CI: 1.04-4.19, p = 0.035). The CD14 -260 C/T SNP did not alter the overall risk for BSI in ventilated VLBW infants. Multiple BSI episodes were more common in the TT genotype group (CC: 17%, CT: 11%, TT: 30%, p = 0.022). This effect was due to the strong effect of the TT genotype on the incidence of multiple BSI in AA infants (CC: 15%, CT: 11%, TT: 39%, p = 0.003). CONCLUSION: The IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T SNPs may alter risk for BSI in ventilated VLBW infants.

Interleukin-10 -1082 G/A polymorphism and risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants.

IL-10 is an anti-inflammatory cytokine that may have a protective role in acute lung injury. IL-10 expression is affected by a single-nucleotide polymorphism (SNP) located at position -1082 (G to A). The A allele is associated with lower IL-10 production. Low IL-10 production has been linked to the development of BPD. Thus, the IL-10 -1082 SNP may be a genetic risk factor for the development of BPD in the premature newborn. The IL-10 -1082 SNP was determined in 294 (235 African American, 56 Caucasian, and 3 Hispanic) mechanically ventilated very low birth weight (VLBW) infants and compared to outcome (death and/or development of BPD). Differences in groups were analyzed using ANOVA (continuous variables) or chi square (proportions). The frequency of the A allele in our population was 0.62. Thirty-nine (13.3%) infants were homozygous GG, 146 (49.7%) were heterozygous GA, and 109 (37.0%) were homozygous AA. There were no significant differences between genotype groups with respect to ethnic origin, gender, need for surfactant replacement therapy, and isolation of Ureaplasma urealyticum or Mycoplasma hominis from tracheal aspirates at birth. However, AA infants were slightly more mature and of greater birth weight than GA infants (26.9 +/- 0.2 weeks vs. 26.3 +/- 0.2 weeks, P < 0.05, and 940 +/- 22 g vs. 882 +/- 18 g, P < 0.05, respectively). There was no significant effect of the IL-10 -1082 SNP on mortality or the development of BPD (O2 on 28 days or 36 weeks postconceptional age). However, when considered together, the IL-10 -1082 AA/GA genotypes (lower IL-10 production) were associated with a trend toward reduction in risk for the combined outcome of BPD or death (18/39 vs. 80/255, respectively; P = 0.068). The incidence of other complications of prematurity (retinopathy of prematurity, intraventricular hemorrhage, or periventricular leukomalacia) was not different between groups. In conclusion, the IL-10 -1082 G/A SNP does not have a major influence on mortality or the development of BPD in ventilated VLBW infants.

Angiotensin converting enzyme insertion/deletion polymorphism does not alter sepsis outcome in ventilated very low birth weight infants.

OBJECTIVE: This study compared the effect of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms on the incidence and outcome of sepsis in ventilated very low birth weight infants. STUDY DESIGN: Infectious complications were retrospectively determined in 295 (234 African-American, 58 Caucasian and three Hispanic) mechanically ventilated very low birth weight (VLBW) infants (<1500 g at birth) and compared ACE I/D genotype. RESULTS: The incidence of the D allele in the study population was 0.60. A total of 113 (38.3%) infants were homozygous DD, 128 (43.4%) were heterozygous ID and 54 (18.3%) were homozygous II. One or more episodes of late BSI developed in 28 (52%) of 54 infants with the II genotype, 66 (52%) of 128 infants with the ID genotype and 52 (46%) of 113 infants with the DD genotype (p=0.618). Neither the rates of non-CONS BSI (II: 24%, ID: 23%, DD: 22%; p=0.937) nor multiple bacteremic/fungemic episodes (II: 13%, ID: 16%, DD: 12%; p=0.641) were different between genotype groups. The ACE I/D polymorphism had no effect on sepsis-related mortality (II: 7%, ID: 5%, DD: 4%; p=0.692). Sepsis mortality for infants with late BSI was 14% in infants with the II genotype, 9% with the ID genotype and 10% with the DD genotype (p=0.764). CONCLUSIONS: The ACE I/D polymorphism does not have a significant effect on the incidence or outcome of sepsis in ventilated VLBW infants.

The Angiotensin Converting Enzyme Insertion/Deletion polymorphism is not associated with an increased risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants.

BACKGROUND: The ACE gene contains a polymorphism consisting of either the presence (insertion, I) or absence (deletion, D) of a 287 bp alu repeat in intron 16. The D allele is associated with increased ACE activity in both tissue and plasma. The DD genotype is associated with risk of developing ARDS and mortality. The frequency of the D allele is higher in patients with pulmonary fibrosis, sarcoidosis and berylliosis. The role of this polymorphism has not been studied in the development of BPD in the premature newborn. METHODS: ACE I/D genotype was determined in 245 (194 African-American, 47 Caucasian and 4 Hispanic) mechanically ventilated infants weighing less than 1250 grams at birth and compared to outcome (death and/or development of BPD). RESULTS: The incidence of the D allele in the study population was 0.58. Eighty-eight (35.9%) infants were homozygous DD, 107 (43.7%) were heterozygous ID and 50 (20.4%) were homozygous II. There were no significant differences between genotype groups with respect to ethnic origin, birth weight, gestation, or gender. There was no effect of the ACE I/D polymorphism on mortality or development of BPD (O2 on 28 days or 36 weeks PCA). Secondary outcomes (intraventricular hemorrhage and periventricular leukomalacia) similarly were not influenced by the ACE ID polymorphism. CONCLUSIONS: The ACE I/D polymorphism does not significantly influence the development of BPD in ventilated infants less than 1250 grams.

Elevated platelet-derived growth factor-BB concentrations in premature neonates who develop chronic lung disease.

BACKGROUND: Chronic lung disease (CLD) in the preterm newborn is associated with inflammation and fibrosis. Platelet-derived growth factor-BB (PDGF-BB), a potent chemotactic growth factor, may mediate the fibrotic component of CLD. The objectives of this study were to determine if tracheal aspirate (TA) concentrations of PDGF-BB increase the first 2 weeks of life in premature neonates undergoing mechanical ventilation for respiratory distress syndrome (RDS), its relationship to the development of CLD, pulmonary hemorrhage (PH) and its relationship to airway colonization with Ureaplasma urealyticum (Uu). METHODS: Infants with a birth weight less than 1500 grams who required mechanical ventilation for RDS were enrolled into this study with parental consent. Tracheal aspirates were collected daily during clinically indicated suctioning. Uu cultures were performed on TA collected in the first week of life. TA supernatants were assayed for PDGF-BB and secretory component of IgA concentrations using ELISA techniques. RESULTS: Fifty premature neonates were enrolled into the study. Twenty-eight infants were oxygen dependent at 28 days of life and 16 infants were oxygen dependent at 36 weeks postconceptual age. PDGF-BB concentrations peaked between 4 and 6 days of life. Maximum PDGF-BB concentrations were significantly higher in infants who developed CLD or died from respiratory failure. PH was associated with increased risk of CLD and was associated with higher PDGF-BB concentrations. There was no correlation between maximum PDGF-BB concentrations and Uu isolation from the airway. CONCLUSIONS: PDGF-BB concentrations increase in TAs of infants who undergo mechanical ventilation for RDS during the first 2 weeks of life and maximal concentrations are greater in those infants who subsequently develop CLD. Elevation in lung PDGF-BB may play a role in the development of CLD.

Tumor necrosis factor alpha -- 308 polymorphism associated with increased sepsis mortality in ventilated very low birth weight infants.

BACKGROUND: Sepsis commonly complicates the clinical course of critically ill very low birth weight infants, with as many as 30% developing hospital-acquired bacteremia. The tumor necrosis factor alpha (TNF-alpha) -- 308 G/A single nucleotide polymorphism (SNP) is associated with adverse outcome in septic adult patients. METHODS: One hundred seventy-three mechanically ventilated very low birth weight infants were genotyped for the TNF-alpha -- 308 G/A SNP. RESULTS: One hundred twenty (69%) infants were homozygous GG, 45 (26%) were heterozygous AG and 8 (5%) were homozygous AA; 2 of 120 (2%) infants developed early bacteremia in the GG group, and 1 of 53 (2%) developed early bacteremia in the AA/AG group (P = 0.919). One or more episodes of late bacteremia/fungemia developed in 59 of 120 (49%) infants with the GG genotype and 23 of 53 (43%) infants with the AG/AA genotype (P = 0.484). Endotracheal tube colonization rates were 65 of 120 (54%) for infants with the GG genotypes and 28 of 53 (53%) for infants with the AG/AA genotypes (P = 0.871). Nosocomial pneumonia developed in a similar number of infants in both genotype groups (9 of 120 infants vs. 3 of 53 infants; P = 0.461). Mortality from sepsis was 3 times greater in infants with the AA/AG genotypes than in those with the GG genotype (10%vs. 3%; P = 0.038). This difference in sepsis mortality was even greater when only bacteremic/fungemic infants are considered (4 of 59 infants vs. 6 of 23 infants; P = 0.026). CONCLUSIONS: These data suggest that the TNF-alpha -- 308 A allele does not affect the development of sepsis in ventilated premature infants but may increase mortality once sepsis develops.

Aggressive early total parental nutrition in low-birth-weight infants.

OBJECTIVE: This study aimed to compare nitrogen balance and biochemical tolerance of early aggressive versus late total parenteral nutrition in very-low-birth-weight (VLBW) infants over the first week of life. STUDY DESIGN: In all, 32 ventilator-dependent preterm infants were prospectively randomized into two groups. The Early Total Parenteral Nutrition (ETPN) group received 3.5 g/kilo-day amino acids (AA), and 3 g/kilo-day of 20% Intralipid (IL), starting within 1 hour after birth. The Late Total Parenteral Nutrition group (LTPN), started on a solution containing glucose during the first 48 hours of life, followed by 2 g/kilo-day of AA and 0.5 g/kilo-day of IL. For the LTPN group AA and IL were each increased by 0.5 g/kilo-day to a maximum of 3.5 and 3 g/kilo-day, respectively. RESULTS: Nitrogen retention was significantly greater in all infants in the ETPN group throughout the 7-day study period. All infants in the LTPN group were in negative nitrogen balance during the first 48 hours of life, while those in the ETPN group were in positive nitrogen balance throughout. The mean (+/-SD) nitrogen retention in the ETPN was 384.5 mg/kilo-day (+/-20.2), compared to 203.4 mg/kilo-day (+/-20.9) in the LTPN group (p <0.001). In each of the first 5 days of life, energy intake was significantly greater in the ETPN group compared to the LTPN group (p <0.001). Mean fluid intake during the study period was similar between, the ETPN and the LTPN groups (162 and 165 cm3/kilo-day, respectively). The mean weight gain was similar in the ETPN and LTPN groups. Plasma levels of cholesterol, triglycerides, bicarbonate, blood urea nitrogen, creatinine, and pH were similar in both groups during the study period. Mean (+/-SD) serum glucose in the LTPN group was higher, but remained in normal range (101.1+/-5.2 and 80.8+/-5.4 mg/kilo-day, respectively). The mean peak serum bilirubin was significantly higher in the ETPN group, compared to The LTPN group (7.7 and 6.2 mg/dl). CONCLUSION: This study shows that aggressive intake of AA and IL can be tolerated immediately after birth by VLBW infants. Also, ETPN significantly increased positive nitrogen balance and caloric intake, without increasing the risk of metabolic acidosis, hypercholesterolemia, or hypertriglyceridemia.

CC chemokine concentrations increase in respiratory distress syndrome and correlate with development of bronchopulmonary dysplasia.

Inflammation is one of the primary processes underlying respiratory distress syndrome (RDS) and its evolution into bronchopulmonary dysplasia (BPD). Recruitment and subsequent activation of macrophages in the lung are mediated by CC chemokines. The role of CC chemokines has not been extensively studied in the course of RDS. Serial tracheal aspirates (TA) were obtained from 56 mechanically ventilated infants with birth weights less than 1,500 g during intervals in the first 21 days of life. Tracheal aspirate concentrations of monocyte chemoattractant proteins-1,2,3 (MCP-1,2,3) and macrophage inflammatory proteins-1alpha and -1beta (MIP-1alpha, MIP-1beta) were determined by enzyme-linked immunosorbent assay (ELISA). Tracheal aspirate concentrations of MCP-1, MCP-2, MCP-3, and MIP-1beta increased during the first week of life in infants with RDS, whereas MIP-1alpha concentrations did not increase appreciably. Increased TA cytokine concentrations were associated with the development of BPD. Maximal TA concentrations of MCP-1, MCP-2, MCP-3, MIP-1alpha, and MIP-1beta were significantly higher in infants who were oxygen-dependent at 28 postnatal days compared to infant who were not. Similarly, maximal TA MCP-1, MCP-2, and MCP-3 but not MIP-1alpha and MIP-1beta concentrations were significantly higher in infants who were oxygen-dependent at 36 weeks of postconceptional age (PCA) than those who were not oxygen-dependent at 36 weeks PCA. Histologic chorioamnionitis and isolation of Ureaplasma urealyticum from the airways were associated with higher maximal TA concentrations of MIP-1alpha and MIP-1beta. Pulmonary hemorrhage was associated with increased maximal concentrations of MCP-1, MCP-2, and MCP-3. These data suggest a role for CC chemokines in the development of BPD in the newborn infant.

Failure of erythromycin to eliminate airway colonization with ureaplasma urealyticum in very low birth weight infants.

BACKGROUND: Airway colonization of mechanically ventilated very low birth weight infants (birth weight < 1500 grams) by Ureaplasma urealyticum (Uu) is associated with an increased risk of bronchopulmonary dysplasia (BPD). While Uu is sensitive to erythromycin in vitro, the efficacy of intravenous (IV) erythromycin to eliminate Uu from the airways has not been studied. METHODS: 17 very low birth weight infants with Uu positive tracheal aspirate (TA) cultures were randomized to either 5 (8 infants) or 10 days (9 infants) of IV erythromycin lactobionate (40 mg/kg/day in 3 divided doses). Tracheal aspirate cultures for Uu were performed on days 0, 5, 10 and 15. RESULTS: Intravenous erythromycin failed to eliminate airway colonization in a large proportion of infants regardless of whether they received 5 or 10 days of treatment. Ureaplasma urealyticum was isolated from 4/15 (27%) of TAs obtained at 5 days, 5/12 TAs (42%) obtained at 10 days and 6/11(55%) TAs obtained at 15 days (combined group data). CONCLUSIONS: Erythromycin administered IV does not eliminate Uu from the airways in a large proportion of infants. Failure of erythromycin to eliminate Uu from the airways may contribute to the lack of efficacy of this drug in reducing the incidence of BPD in very low birth weight infants.