Predicting death or extended length of stay in infants with congenital diaphragmatic hernia.

OBJECTIVE: To predict mortality or length of stay (LOS) >109 days (90th percentile) among infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We conducted a retrospective analysis using the Children's Hospital Neonatal Database during 2010 to 2014. Infants born >34 weeks gestation with CDH admitted at 22 participating regional neonatal intensive care units were included; patients who were repaired or were at home before admission were excluded. The primary outcome was death before discharge or LOS >109 days. Factors associated with this outcome were used to develop a multivariable equation using 80% of the cohort. Validation was performed in the remaining 20% of infants. RESULTS: The median gestation and age at referral in this cohort (n=677) were 38 weeks and 6 h, respectively. The primary outcome occurred in 242 (35.7%) infants, and was distributed between mortality (n=180, 27%) and LOS >109 days (n=66, 10%). Regression analyses showed that small for gestational age (odds ratio (OR) 2.5, P=0.008), presence of major birth anomalies (OR 5.9, P<0.0001), 5- min Apgar score ⩽3 (OR 7.0, P=0.0002), gradient of acidosis at the time of referral (P<0.001), the receipt of extracorporeal support (OR 8.4, P<0.0001) and bloodstream infections (OR 2.2, P=0.004) were independently associated with death or LOS >109 days. This model performed well in the validation cohort (area under curve (AUC)=0.856, goodness-of-fit (GF) χ(2), P=0.16) and acted similarly even after omitting extracorporeal support (AUC=0.82, GF χ(2), P=0.05). CONCLUSIONS: Six variables predicted death or LOS ⩾109 days in this large, contemporary cohort with CDH. These results can assist in risk adjustment for comparative benchmarking and for counseling affected families.

How to Reduce Head CT Orders in Children with Hydrocephalus Using the Lean Six Sigma Methodology: Experience at a Major Quaternary Care Academic Children's Center.

BACKGROUND AND PURPOSE: Lean Six Sigma methodology is increasingly used to drive improvement in patient safety, quality of care, and cost-effectiveness throughout the US health care delivery system. To demonstrate our value as specialists, radiologists can combine lean methodologies along with imaging expertise to optimize imaging elements-of-care pathways. In this article, we describe a Lean Six Sigma project with the goal of reducing the relative use of pediatric head CTs in our population of patients with hydrocephalus by 50% within 6 months. MATERIALS AND METHODS: We applied a Lean Six Sigma methodology using a multidisciplinary team at a quaternary care academic children's center. The existing baseline imaging practice for hydrocephalus was outlined in a Kaizen session, and potential interventions were discussed. An improved radiation-free workflow with ultrafast MR imaging was created. Baseline data were collected for 3 months by using the departmental radiology information system. Data collection continued postintervention and during the control phase (each for 3 months). The percentage of neuroimaging per technique (head CT, head ultrasound, ultrafast brain MR imaging, and routine brain MR imaging) was recorded during each phase. RESULTS: The improved workflow resulted in a 75% relative reduction in the percentage of hydrocephalus imaging performed by CT between the pre- and postintervention/control phases (Z-test, P = .0001). CONCLUSIONS: Our lean interventions in the pediatric hydrocephalus care pathway resulted in a significant reduction in head CT orders and increased use of ultrafast brain MR imaging.

Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children's Hospitals Neonatal Consortium HIE focus group.

OBJECTIVE: To characterize infants affected with perinatal hypoxic ischemic encephalopathy (HIE) who were referred to regional neonatal intensive care units (NICUs) and their related short-term outcomes. STUDY DESIGN: This is a descriptive study evaluating the data collected prospectively in the Children's Hospital Neonatal Database, comprised of 27 regional NICUs within their associated children's hospitals. A consecutive sample of 945 referred infants born ⩾36 weeks' gestation with perinatal HIE in the first 3 days of life over approximately 3 years (2010-July 2013) were included. Maternal and infant characteristics are described. Short-term outcomes were evaluated including medical comorbidities, mortality and status of survivors at discharge. RESULT: High relative frequencies of maternal predisposing conditions, cesarean and operative vaginal deliveries were observed. Low Apgar scores, profound metabolic acidosis, extensive resuscitation in the delivery room, clinical and electroencephalographic (EEG) seizures, abnormal EEG background and brain imaging directly correlated with the severity of HIE. Therapeutic hypothermia was provided to 85% of infants, 15% of whom were classified as having mild HIE. Electrographic seizures were observed in 26% of the infants. Rates of complications and morbidities were similar to those reported in prior clinical trials and overall mortality was 15%. CONCLUSION: Within this large contemporary cohort of newborns with perinatal HIE, the application of therapeutic hypothermia and associated neurodiagnostic studies appear to have expanded relative to reported clinical trials. Although seizure incidence and mortality were lower compared with those reported in the trials, it is unclear whether this represented improved outcomes or therapeutic drift with the treatment of milder disease.

Short-term outcomes for preterm infants with surgical necrotizing enterocolitis.

OBJECTIVE: To characterize the population and short-term outcomes in preterm infants with surgical necrotizing enterocolitis (NEC). STUDY DESIGN: Preterm infants with surgical NEC were identified from 27 hospitals over 3 years using the Children's Hospitals Neonatal Database; infants with gastroschisis, volvulus, major congenital heart disease or surgical NEC that resolved prior to referral were excluded. Patient characteristics and pre-discharge morbidities were stratified by gestational age (<28 vs 28(0/7) to 36(6/7) weeks' gestation). RESULT: Of the 753 eligible infants, 60% were born at <28 weeks' gestation. The median age at referral was 14 days; only 2 infants were inborn. Male gender (61%) was overrepresented, whereas antenatal steroid exposure was low (46%). Although only 11% had NEC totalis, hospital mortality (<28 weeks' gestation: 41%; 28(0/7) to 36(6/7) weeks' gestation: 32%, P=0.02), short bowel syndrome (SBS)/intestinal failure (IF) (20% vs 26%, P=0.06) and the composite of mortality or SBS/IF (50% vs 49%, P=0.7) were prevalent. Also, white matter injury (11.7% vs 6.6%, P=0.02) and grade 3 to 4 intraventricular hemorrhages (23% vs 2.7%, P<0.01) were commonly diagnosed. After referral, the median length of hospitalization was longer for survivors (106 days; interquartile range (IQR) 79, 152) relative to non-survivors (2 days; IQR 1,17; P<0.001). These survivors were prescribed parenteral nutrition infrequently after hospital discharge (<28 weeks': 5.2%; 28(0/7) to 36(6/7) weeks': 9.9%, P=0.048). CONCLUSION: After referral for surgical NEC, the short-term outcomes are grave, particularly for infants born <28 weeks' gestation. Although analyses to predict outcomes are urgently needed, these data suggest that affected infants are at a high risk for lengthy hospitalizations and adverse medical and neuro-developmental abnormalities.

The Children's Hospitals Neonatal Database: an overview of patient complexity, outcomes and variation in care.

The Children's Hospitals Neonatal Consortium is a multicenter collaboration of leaders from 27 regional neonatal intensive care units (NICUs) who partnered with the Children's Hospital Association to develop the Children's Hospitals Neonatal Database (CHND), launched in 2010. The purpose of this report is to provide a first summary of the population of infants cared for in these NICUs, including representative diagnoses and short-term outcomes, as well as to characterize the participating NICUs and institutions. During the first 2 1/2 years of data collection, 40910 infants were eligible. Few were born inside these hospitals (2.8%) and the median gestational age at birth was 36 weeks. Surgical intervention (32%) was common; however, mortality (5.6%) was infrequent. Initial queries into diagnosis-specific inter-center variation in care practices and short-term outcomes, including length of stay, showed striking differences. The CHND provides a contemporary, national benchmark of short-term outcomes for infants with uncommon neonatal illnesses. These data will be valuable in counseling families and for conducting observational studies, clinical trials and collaborative quality improvement initiatives.

Predicting death or tracheostomy placement in infants with severe bronchopulmonary dysplasia.

OBJECTIVE: To estimate the risk of death or tracheostomy placement (D/T) in infants with severe bronchopulmonary dysplasia (sBPD) born < 32 weeks' gestation referred to regional neonatal intensive care units. STUDY DESIGN: We conducted a retrospective cohort study in infants born < 32 weeks' gestation with sBPD in 2010-2011, using the Children's Hospital Neonatal Database. sBPD was defined as the need for FiO2 ⩾ 0.3, nasal cannula support >2 l min(-1) or positive pressure at 36 weeks' post menstrual age. The primary outcome was D/T before discharge. Predictors associated with D/T in bivariable analyses (P < 0.2) were used to develop a multivariable logistic regression equation using 80% of the cohort. This equation was validated in the remaining 20% of infants. RESULT: Of 793 eligible patients, the mean gestational age was 26 weeks' and the median age at referral was 6.4 weeks. D/T occurred in 20% of infants. Multivariable analysis showed that later gestational age at birth, later age at referral along with pulmonary management as the primary reason for referral, mechanical ventilation at the time of referral, clinically diagnosed pulmonary hypertension, systemic corticosteroids after referral and occurrence of a bloodstream infection after referral were each associated with D/T. The model performed well with validation (area under curve 0.86, goodness-of-fit χ(2), P = 0.66). CONCLUSION: Seven clinical variables predicted D/T in this large, contemporary cohort with sBPD. These results can be used to inform clinicians who counsel families of affected infants and to assist in the design of future prospective trials.

Characterization of peripheral nerve sheath tumors with 3T proton MR spectroscopy.

BACKGROUND AND PURPOSE: The characterization of peripheral nerve sheath tumors is challenging. The purpose here was to investigate the diagnostic value of quantitative proton MR spectroscopy at 3T for the characterization of peripheral nerve sheath tumors as benign or malignant, compared with PET. MATERIALS AND METHODS: Twenty participants with 24 peripheral nerve sheath tumors underwent MR spectroscopy by use of a point-resolved sequence (TE, 135 ms). Six voxels were placed in 4 histologically proven malignant peripheral nerve sheath tumors and 22 voxels in 20 benign peripheral nerve sheath tumors (9 histologically proven, 11 with documented stability). The presence or absence of a trimethylamine signal was evaluated, the trimethylamine concentration estimated by use of phantom replacement methodology, and the trimethylamine fraction relative to Cr measured. MR spectroscopy results for benign and malignant peripheral nerve sheath tumors were compared by use of a Mann-Whitney test, and concordance or discordance with PET findings was recorded. RESULTS: In all malignant tumors and in 9 of 18 benign peripheral nerve sheath tumors, a trimethylamine peak was detected, offering the presence of trimethylamine as a sensitive (100%), but not specific (50%), marker of malignant disease. Trimethylamine concentrations (2.2 ± 2.8 vs 6.6 ± 5.8 institutional units; P < .049) and the trimethylamine fraction (27 ± 42 vs 88 ± 22%; P < .012) were lower in benign than malignant peripheral nerve sheath tumors. A trimethylamine fraction threshold of 50% resulted in 100% sensitivity (95% CI, 58.0%-100%) and 72.2% (95% CI, 59.5%-75%) specificity for distinguishing benign from malignant disease. MR spectroscopy and PET results were concordant in 12 of 16 cases, (2 false-positive results for MR spectroscopy and PET each). CONCLUSIONS: Quantitative measurement of trimethylamine concentration by use of MR spectroscopy is feasible in peripheral nerve sheath tumors and shows promise as a method for the differentiation of benign and malignant lesions. Trimethylamine presence within a peripheral nerve sheath tumor is a sensitive marker of malignant disease, but quantitative measurement of trimethylamine content is required to improve specificity.

Therapeutic interventions and short-term outcomes for infants with severe bronchopulmonary dysplasia born at <32 weeks' gestation.

OBJECTIVE: To characterize the treatments and short-term outcomes in infants with severe bronchopulmonary dysplasia (sBPD) referred to regional neonatal intensive care units. STUDY DESIGN: Infants born <32 weeks' gestation with sBPD were identified using the Children's Hospital Neonatal Database. Descriptive outcomes are reported. RESULT: A total of 867 patients were eligible. On average, infants were born at 26 weeks' gestation and referred 43 days after birth. Infants frequently experienced lung injury (pneumonia: 24.1%; air leak: 9%) and received systemic corticosteroids (61%) and mechanical ventilation (median duration 37 days). Although 91% survived to discharge, the mean post-menstrual age was 47 weeks. Ongoing care such as supplemental oxygen (66%) and tracheostomy (5%) were frequently needed. CONCLUSION: Referred infants with sBPD sustain multiple insults to lung function and development. Because affected infants have no proven, safe or efficacious therapy and endure an exceptional burden of care even after referral, urgent work is required to observe and improve their outcomes.

Feto-maternal vitamin D status and infant whole-body bone mineral content in the first weeks of life.

BACKGROUND/OBJECTIVES: Compromised vitamin D status is common in pregnancy and may have adverse impacts on fetal development. The purpose of this study was to investigate the association of infant whole-body bone mineral content (WBBMC) at 8-21 days of age with feto-maternal vitamin D status in a multiethnic population in Oakland, California. SUBJECTS/METHODS: This was a cross-sectional study of 120 women and their newborn infants. Maternal and cord blood were collected at delivery. WBBMC was measured by dual-energy X-ray absorptiometry in term-born infants 8-21 days post birth. RESULTS: No significant association was observed between unadjusted or size-adjusted WBBMC and feto-maternal vitamin D status analyzed continuously or categorically. In multivariate modeling, unadjusted WBBMC was predicted by bone area (P<0.0001), weight-for-age (P<0.0001) and weight-for-length (P=0.0005) Z-scores, but not by feto-maternal vitamin D status. Anthropometric predictors but not vitamin D remained significant in the multivariate model after adjustment of WBBMC for weight, bone area (bone mineral density) or logarithmically derived exponents of the denominators. CONCLUSIONS: Results of the present study do not support an association between feto-maternal vitamin D status and early infant WBBMC, raw or adjusted for inter-individual differences in size, in a multiethnic population in Northern California.

The role of magnetic resonance imaging in the diagnostic evaluation of malignant peripheral nerve sheath tumors.

BACKGROUND AND AIMS: Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of mortality in patients with neurofibromatosis type-1 (NF1)); however, they may also arise sporadically. Differences in magnetic resonance imaging (MRI) features between MPNSTs arising in NF1 subjects versus non-NF1 subjects have not been studied before. The accuracy of MRI in distinguishing MPNSTs from benign peripheral nerve sheath tumors (BPNSTs) has also been debated. The objective of this study was to determine the potential differentiating MRI features between (a) NF1-related and non-NF1-related MPNSTs and (b) MPNSTs and BPNSTs. MATERIALS AND METHODS: We retrospectively evaluated the MRI studies of 21 patients (12 NF1 subjects and nine non-NF1 subjects) with MPNSTs and 35 patients with BPNSTs. In all studies, the lesions were assessed in terms of size, margins, T1 and T2 signal characteristics, internal architecture, pattern of contrast enhancement, invasion of adjacent structures and necrosis/cystic degeneration as well as for the presence of tail-, target- and split-fat signs. RESULTS: MPNSTs of NF1 subjects occurred at an earlier age and displayed a higher incidence of necrosis/cystic degeneration compared with MPNSTs of non-NF1 subjects. Compared with BPNSTs, MPNSTs were significantly larger at the time of diagnosis and demonstrated a higher incidence of ill-defined margins (specificity 91%, sensitivity 52%) and invasion of adjacent structures (specificity 100%, sensitivity 43%). CONCLUSIONS: Differences exist between NF1-related and non-NF1-related MPNSTs regarding the age of occurrence and MRI appearance. In the MRI evaluation of peripheral nerve sheath tumors, the presence of ill-defined tumor margins and/or invasion of adjacent structures are highly specific for malignancy.

Pilot trial of late booster doses of surfactant for ventilated premature infants.

OBJECTIVE: Many premature infants at risk for bronchopulmonary dysplasia experience episodes of surfactant dysfunction with reduced surfactant protein B (SP-B). In this study, we investigated the safety and responses to booster doses of surfactant. STUDY DESIGN: A total of 87 infants, 500 to 1250 g birth weight, who were ventilated at 7 to 10 days received 2 or 3 doses of Infasurf (Calfactant, Forest Pharmaceuticals, St Louis, MO, USA) within a 1-week period. RESULT: For 184 doses, occurrence rates of transient bradycardia (13) and plugged endotracheal tube (5) were low, and no other adverse effects were noted. Treatment transiently improved the respiratory severity score (FiO(2) × mean airway pressure), SP-B content (+75%) and surface properties of isolated surfactant. Levels of eight proinflammatory cytokines in tracheal aspirate were interrelated and unchanged from baseline after surfactant treatment. CONCLUSION: Booster doses of surfactant for premature infants with lung disease are safe and transiently improve respiratory status as well as composition and function of endogenous surfactant.

No enhancement of fusion probability by the neutron halo of 6He.

Quantum tunnelling through a potential barrier (such as occurs in nuclear fusion) is very sensitive to the detailed structure of the system and its intrinsic degrees of freedom. A strong increase of the fusion probability has been observed for heavy deformed nuclei. In light exotic nuclei such as 6He, 11Li and 11Be (termed 'halo' nuclei), the neutron matter extends much further than the usual nuclear interaction scale. However, understanding the effect of the neutron halo on fusion has been controversial--it could induce a large enhancement of fusion, but alternatively the weak binding energy of the nuclei could inhibit the process. Other reaction channels known as direct processes (usually negligible for ordinary nuclei) are also important: for example, a fragment of the halo nucleus could transfer to the target nucleus through a diminished potential barrier. Here we study the reactions of the halo nucleus 6He with a 238U target, at energies near the fusion barrier. Most of these reactions lead to fission of the system, which we use as an experimental signature to identify the contribution of the fusion and transfer channels to the total cross-section. At energies below the fusion barrier, we find no evidence for a substantial enhancement of fusion. Rather, the (large) fission yield is due to a two-neutron transfer reaction, with other direct processes possibly also involved.

Binding of correolide to the K(v)1.3 potassium channel: characterization of the binding domain by site-directed mutagenesis.

Correolide is a novel immunosuppressant that inhibits the voltage-gated potassium channel K(v)1.3 [Felix et al. (1999) Biochemistry 38, 4922-4930]. [(3)H]Dihydrocorreolide (diTC) binds with high affinity to membranes expressing homotetrameric K(v)1.3 channels, and high affinity diTC binding can be conferred to the diTC-insensitive channel, K(v)3.2, after substitution of three nonconserved residues in S(5) and S(6) with the corresponding amino acids present in K(v)1.3 [Hanner et al. (1999) J. Biol. Chem. 274, 25237-25244]. Site-directed mutagenesis along S(5) and S(6) of K(v)1.3 was employed to identify those residues that contribute to high affinity binding of diTC. Binding of monoiodotyrosine-HgTX(1)A19Y/Y37F ([(125)I]HgTX(1)A19Y/Y37F) in the external vestibule of the channel was used to characterize each mutant for both tetrameric channel formation and levels of channel expression. Substitutions at Leu(346) and Leu(353) in S(5), and Ala(413), Val(417), Ala(421), Pro(423), and Val(424) in S(6), cause the most dramatic effect on diTC binding to K(v)1.3. Some of the critical residues in S(6) appear to be present in a region of the protein that alters its conformation during channel gating. Molecular modeling of the S(5)-S(6) region of K(v)1.3 using the X-ray coordinates of the KcsA channel, and other experimental constraints, yield a template that can be used to dock diTC in the channel. DiTC appears to bind in the water-filled cavity below the selectivity filter to a hydrophobic pocket contributed by the side chains of specific residues. High affinity binding is predicted to be determined by the complementary shape between the bowl-shape of the cavity and the shape of the ligand. The conformational change that occurs in this region of the protein during channel gating may explain the state-dependent interaction of diTC with K(v)1.3.

Early high-frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation in very low birth weight infants: a pilot study of two ventilation protocols.

OBJECTIVE: To evaluate the feasibility of conducting a prospective, randomized trial comparing early high-frequency oscillatory ventilation (HFOV) to synchronized intermittent mandatory ventilation (SIMV) in very low birth weight (VLBW) premature infants. This pilot study evaluated two ventilator management protocols to determine how well they could be implemented in a multicenter clinical trial. Although this pilot study was not powered to detect differences in outcome, we also collected outcome data. DESIGN: Prospective, multicenter, randomized pilot study. SETTING: Seven tertiary-level intensive care nurseries with previous experience with both HFOV and flow-triggered SIMV. PATIENTS: Fifty infants weighing 501 to 1200 g, less than 4 hours of age, who had received one dose of surfactant and required ventilation with mean airway pressure > or =6 cm H2O and F(I)O2 > or =0.25, and had an anticipated duration of ventilation greater than 24 hours. INTERVENTIONS: Patients were stratified by birth weight and prenatal steroid status, then randomized to either HFOV or SIMV with tidal volume monitoring. Ventilator management for patients in both study arms was strictly governed by protocols that included optimizing lung inflation and blood gases, weaning strategies, and extubation criteria. MEASUREMENTS: Data were collected using the tools planned for the larger collaborative study. Protocol compliance was closely monitored, with successive changes in the protocol made as necessary to improve clarity and increase compliance. The incidence of major neonatal adverse outcomes was recorded. MAIN RESULTS: Data are presented for 24 HFOV and 24 SIMV infants (two infants, twins, were withdrawn from the study at parent's request). Nineteen of the 24 HFOV infants and 20 of the 24 SIMV infants survived to 36 weeks corrected age. Age at final extubation for survivors was 16+/-16 (mean+/-SD) days for HFOV infants and 24+/-24 days for SIMV infants. At 36 weeks corrected age, 14 of the 19 HFOV survivors were extubated and in room air, whereas 5 required supplemental oxygen. In comparison, 6 of the 20 SIMV survivors were extubated and in room air, whereas 14 required supplemental oxygen. Grade III/IV IVH and/or periventricular leukomalacia occurred in 2 HFOV and 2 SIMV patients. Overall compliance with the ventilator protocols was 82% for the SIMV protocol, and 88% for the HFOV protocol. CONCLUSIONS: The preliminary outcome data supports conducting the large randomized trial, which began in July of 1998. The protocols for the ventilator management of VLBW infants, both with HFOV and with SIMV were easily implemented and consistently followed, and are presented here.

Thrombolytic therapy for adhesion of percutaneous central venous catheters to vein intima associated with Malassezia furfur Infection.

OBJECTIVE: To report our experience with thrombolytic agents in the management of two infants with silicone central venous catheters that had adhered to the vein wall as a result of infection with Malassezia furfur. STUDY DESIGN: Case review of two very low birth weight infants with adherent central venous catheters. RESULTS: Treatment with urokinase and tissue plasminogen activator facilitated the removal of these catheters without breakage or surgical intervention. CONCLUSIONS: Thrombolytic agents should be considered as a treatment of adhered catheters, as well as of occluded catheters.

Neonatal high-frequency ventilation. Past, present, and future.

High-frequency ventilation has become established as an effective treatment modality in a variety of clinical situations. The laboratory and clinical investigations of these techniques have contributed tremendously to our understanding of the pathophysiology of respiratory failure and the important concept of maintaining adequate lung volume. Clinicians have come to appreciate better the factors involved in lung injury and the potential for damage to distant organs. The place of HFV in the therapeutic armamentarium will undoubtedly continue to evolve in the years to come. Of particular interest is the advent of advanced modes of fully synchronized and volume-targeted conventional mechanical ventilatory modes, along with the trend to use smaller tidal volumes and higher levels of PEEP with conventional ventilation. With these developments there seems to be a certain convergence of HFV and tidal ventilation that is the logical result of our improved understanding of respiratory pathophysiology. The available controlled trials of HFV versus tidal ventilation do not clearly differentiate whether improved outcomes are the result of HFV per se, or a reflection of the effects of optimizing lung volume, a benefit that may not be unique to HFV.

Chiral asymmetry in spiral galaxies?

Spiral galaxies are chiral entities when coupled with the direction of their recession velocity. As viewed from the Earth, the S-shaped and Z-shaped spiral galaxies are two chiral forms. What is the nature of chiral symmetry in spiral galaxies? In the Carnegie Atlas of Galaxies that lists photographs of a total of 1,168 galaxies, we found 540 galaxies, classified as normal or barred spirals, that are clearly identifiable as S- or Z- type. The recession velocities for 538 of these galaxies could be obtained from this atlas and other sources. A statistical analysis of this sample reveals no overall asymmetry but there is a significant asymmetry in certain subclasses: dominance of S-type galaxies in the Sb class of normal spiral galaxies and a dominance of Z-type in the SBb class of barred spiral galaxies. Both S- and Z-type galaxies seem to have similar velocity distribution, indicating no spatial segregation of the two chiral forms.

Peptide aldehyde inhibitors of bacterial peptide deformylases.

Bacterial peptide deformylases (PDF, EC 3.5.1.27) are metalloenzymes that cleave the N-formyl groups from N-blocked methionine polypeptides. Peptide aldehydes containing a methional or norleucinal inhibited recombinant peptide deformylase from gram-negative Escherichia coli and gram-positive Bacillus subtilis. The most potent inhibitor was calpeptin, N-CBZ-Leu-norleucinal, which was a competitive inhibitor of the zinc-containing metalloenzymes, E. coli and B. subtilis PDF with Ki values of 26.0 and 55.6 microM, respectively. Cobalt-substituted E. coli and B. subtilis deformylases were also inhibited by these aldehydes with Ki values for calpeptin of 9.5 and 12.4 microM, respectively. Distinct spectral changes were observed upon binding of calpeptin to the Co(II)-deformylases, consistent with the noncovalent binding of the inhibitor rather than the formation of a covalent complex. In contrast, the chelator 1,10-phenanthroline caused the time-dependent inhibition of B. subtilis Co(II)-PDF activity with the loss of the active site metal. The fact that calpeptin was nearly equipotent against deformylases from both gram-negative and gram-positive bacterial sources lends further support to the idea that a single deformylase inhibitor might have broad-spectrum antibacterial activity.

Disruption of barrier function in neonatal skin associated with adhesive removal.

OBJECTIVE: Patients in the neonatal intensive care unit require life support and monitoring equipment that must be securely attached to the skin; removal or replacement often causes skin trauma. In this study, we compared the effects of application and removal of three different adhesives on the skin barrier function of premature neonates. The effects were measured by transepidermal water loss (TEWL), colorimetric measurements, and visual inspection. DESIGN: Thirty neonates, between 26 and 40 weeks of gestational age and with birth weights ranging from 690 to 3000 gm, were enrolled in the study during the first week of life. Pieces of plastic tape (1 cm2), pectin barrier, and hydrophilic gel were applied to previously undisturbed sites on the back. A fourth site was used as a control. We measured TEWL, colorimetric readings, and visual inspection scores of skin irritation and stripping at each of the four sites serially: before adhesive application, 30 minutes after adhesive removal, and 24 hours later. RESULTS: Thirty minutes after adhesive removal, TEWL, colorimetric measurements, and visual inspection scores were all significantly higher at the sites of plastic tape and pectin barrier removal than at the control and gel adhesive sites (p < 0.01), demonstrating greater disruption of skin barrier function with removal of the plastic tape and pectin barrier. When the neonates were divided into three groups on the basis of birth weight (< 1000 gm [n = 10], 1000 to 1500 gm [n = 11], and > 1500 gm [n = 9], the same pattern of greater disruption in skin barrier function, as measured by TEWL, was observed in each birth weight group. Twenty-four hours after adhesive removal, TEWL of the plastic tape and pectin barrier sites were not significantly different from the control site, indicating recovery of skin barrier function. CONCLUSIONS: This study demonstrates that a single application and removal of two commonly used adhesives, plastic tape and pectin barrier, disrupts skin barrier function in neonates of varying gestational ages.