23 results on '"Herkert L"'
Search Results
2. PO-1803: Preventing Radioinduced Injury by Topical Application of an Amifostine Metabolite-Loaded Thermogel
- Author
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Clémenson, C., primary, Liu, W., additional, Bricout, D., additional, Soyez-Herkert, L., additional, Chargari, C., additional, Mondini, M., additional, Haddad, R., additional, Wang-Zang, X., additional, Benel, L., additional, Bloy, C., additional, and Deutsch, E., additional
- Published
- 2020
- Full Text
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3. Therapy at 30 Days of Life Predicts Lung Function at 6-12 Months in Infants with Congenital Diaphragmatic Hernia
- Author
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Chotzoglou, E., primary, Hedrick, H.L., additional, Herkert, L., additional, Rintoul, N., additional, and Panitch, H.B., additional
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- 2019
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4. Eigenschaften und biologische Bedeutung der Desoxyribonuclease aus Säugetierorganen
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Siebert, G., primary, Lang, K., additional, Lucius-Lang, S., additional, Herkert, L., additional, Stark, G., additional, Rossmüller, G., additional, and Jöckel, H., additional
- Published
- 1953
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5. Prevalence and patterns of executive function, adaptive function, and behavioral outcomes in preschool and school age children with congenital diaphragmatic hernia.
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Danzer E, Schreiber JE, Hoffman C, Mathew L, Flohr SJ, Eppley E, Land SD, Herkert L, Rintoul NE, Adzick NS, and Hedrick HL
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- Humans, Child, Preschool, Child, Executive Function, Retrospective Studies, Prevalence, Follow-Up Studies, Hernias, Diaphragmatic, Congenital epidemiology
- Abstract
Background: Executive function, adaptive function, and behavioral outcomes in congenital diaphragmatic hernia (CDH) survivors have not been well studied., Aim: To evaluate executive and neurobehavioral dysfunction in preschool and early school-aged children with CDH., Study Design: Retrospective cohort study., Subjects: All eligible CDH survivors ages 3 to 7 years enrolled in our follow-up program between February 2020 and February 2021., Outcome Measures: The Behavior Rating Inventory of Executive Function (BRIEF), the Adaptive Behavior Assessment System, 2nd Edition (ABAS-II), and the Child Behavior Checklist (CBCL) were used to assess functional and behavioral outcomes. Summary scores were compared to standard population norms., Results: A total of 100 patients were enrolled during the study period. Of those, 73 parents completed at least one of the questionnaires, resulting in completion of the BRIEF, ABAS-II, and CBCL for 63, 68, and 63 patients, respectively. Preschool children had normal executive function (BRIEF-P) while global executive composite (P = 0.012) and the emotional regulation index (P = 0.010) for school age patients (BRIEF-2) were worse. CDH survivors had favorable adaptive functioning (ABAS-II). Mean CBCL scores for preschool attention problems (P = 0.018), school age attention problems (P = 0.001), and attention deficits hyperactivity problems (P = 0.027) were significantly worse. Prematurity, surrogate markers of disease severity, non-white race, and public insurance status were associated with worse neurobehavioral dysfunction in bivariable analysis., Conclusions: The majority of preschool and school age CDH survivors have age-appropriate executive, adaptive and behavioral functioning. CDH survivors, however, have lower executive function and attention scores compared with the general population., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2024
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6. Extracorporeal Membrane Oxygenation for Neonates With Congenital Diaphragmatic Hernia: Prevalence of Seizures and Outcomes.
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Danzer E, Massey SL, Flohr SJ, Mathew L, Hoffman C, Abramson A, Selenski P, Canning CE, Eppley E, Connelly JT, Herkert L, Rintoul NE, Adzick NS, Abend NS, and Hedrick HL
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- Humans, Infant, Newborn, Retrospective Studies, Prevalence, Intensive Care Units, Neonatal, Electroencephalography, Extracorporeal Membrane Oxygenation, Hernias, Diaphragmatic, Congenital diagnosis, Hernias, Diaphragmatic, Congenital therapy, Seizures epidemiology
- Abstract
Objectives: We aimed to determine the prevalence of electrographic seizures and associated odds of adverse outcomes of electrographic seizures in neonates with congenital diaphragmatic hernia (CDH) receiving extracorporeal membrane oxygenation (ECMO)., Design: Retrospective, descriptive case series., Setting: Neonatal ICU (NICU) in a quaternary care institution., Patients: All neonates with CDH receiving ECMO undergoing continuous electroencephalographic monitoring (CEEG) and follow-up between January 2012 and December 2019., Interventions: None., Measurements and Main Results: All eligible neonates with CDH receiving ECMO underwent CEEG (n = 75). Electrographic seizures occurred in 14 of 75 (19%): they were exclusively electrographic-only in nine of 14, both electrographic-only and electroclinical in three of 14, and electroclinical only in two of 14. Two neonates developed status epilepticus. We identified an association between presence of seizures, rather than not, and longer duration of initial session of CEEG monitoring (55.7 hr [48.2-87.3 hr] vs 48.0 hr [43.0-48.3 hr]; p = 0.001). We also found an association between presence of seizures, rather than not, and greater odds of use of a second CEEG monitoring (12/14 vs 21/61; odds ratio [OR], 11.43 [95% CI, 2.34-55.90; p = 0.0026). Most neonates with seizures (10/14), experienced their onset of seizures more than 96 hours after the start of ECMO. Overall, the presence of electrographic seizures, compared with not, was associated with lower odds of survival to NICU discharge (4/14 vs 49/61; OR 0.10 [95% CI 0.03 to 0.37], p = 0.0006). Also, the presence of seizures-rather than not-was associated with greater odds of a composite of death and all abnormal outcomes on follow-up (13/14 vs 26/61; OR, 17.5; 95% CI, 2.15-142.39; p = 0.0074)., Conclusions: Nearly one in five neonates with CDH receiving ECMO developed seizures during the ECMO course. Seizures were predominantly electrographic-only and when present were associated with great odds of adverse outcomes. The current study provides evidence to support standardized CEEG in this population., Competing Interests: Dr. Massey received support for article research from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)
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- 2023
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7. Pathway-Controlled Aqueous Supramolecular Polymerization via Solvent-Dependent Chain Conformation Effects.
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Borsdorf L, Herkert L, Bäumer N, Rubert L, Soberats B, Korevaar PA, Bourque C, Gatsogiannis C, and Fernández G
- Abstract
Solute-solvent interactions play a critical role in multiple fields, including biology, materials science, and (physical) organic, polymer, and supramolecular chemistry. Within the growing field of supramolecular polymer science, these interactions have been recognized as an important driving force for (entropically driven) intermolecular association, particularly in aqueous media. However, to date, solute-solvent effects remain poorly understood in the context of complex self-assembly energy landscapes and pathway complexity. Herein, we unravel the role of solute-solvent interactions in controlling chain conformation effects, allowing energy landscape modulation and pathway selection in aqueous supramolecular polymerization. To this end, we have designed a series of oligo(phenylene ethynylene) (OPE)-based bolaamphiphilic Pt(II) complexes OPE2 - 4 bearing solubilizing triethylene glycol (TEG) chains of equal length on both molecule ends, but a different size of the hydrophobic aromatic scaffold. Strikingly, detailed self-assembly studies in aqueous media disclose a different tendency of the TEG chains to fold back and enwrap the hydrophobic molecular component depending on both the size of the core and the volume fraction of the co-solvent (THF). The relatively small hydrophobic component of OPE2 can be readily shielded by the TEG chains, leading to only one aggregation pathway. In contrast, the decreased capability of the TEG chains to effectively shield larger hydrophobic cores ( OPE3 and OPE4 ) enables different types of solvent quality-dependent conformations (extended, partly back-folded and back-folded), which in turn induce various controllable aggregation pathways with distinct morphologies and mechanisms. Our results shed light on previously underappreciated solvent-dependent chain conformation effects and their role in governing pathway complexity in aqueous media.
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- 2023
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8. Tuning the Molecular Packing of Self-Assembled Amphiphilic Pt II Complexes by Varying the Hydrophilic Side-Chain Length.
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Herkert L, Selter P, Daniliuc CG, Bäumer N, Palakkal JP, Fernández G, and Hansen MR
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Understanding the relationship between molecular design and packing modes constitutes one of the major challenges in self-assembly and is essential for the preparation of functional materials. Herein, we have achieved high precision control over the supramolecular packing of amphiphilic Pt
II complexes by systematic variation of the hydrophilic side-chain length. A novel approach of general applicability based on complementary X-ray diffraction and solid-state NMR spectroscopy has allowed us to establish a clear correlation between molecular features and supramolecular ordering. Systematically increasing the side-chain length gradually increases the steric demand and reduces the extent of aromatic interactions, thereby inducing a gradual shift in the molecular packing from parallel to a long-slipped organization. Notably, our findings highlight the necessity of advanced solid-state NMR techniques to gain structural information for supramolecular systems where single-crystal growth is not possible. Our work further demonstrates a new molecular design strategy to modulate aromatic interaction strengths and packing arrangements that could be useful for the engineering of functional materials based on PtII and aromatic molecules., (© 2020 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)- Published
- 2021
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9. Right Ventricular Strain, Brain Natriuretic Peptide, and Mortality in Congenital Diaphragmatic Hernia.
- Author
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Avitabile CM, Wang Y, Zhang X, Griffis H, Saavedra S, Adams S, Herkert L, Frank DB, Quartermain MD, Rintoul NE, Hedrick HL, and Mercer-Rosa L
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- Heart Ventricles diagnostic imaging, Humans, Infant, Natriuretic Peptide, Brain, Retrospective Studies, Hernias, Diaphragmatic, Congenital complications, Hernias, Diaphragmatic, Congenital diagnostic imaging, Hernias, Diaphragmatic, Congenital surgery, Ventricular Dysfunction, Right diagnostic imaging
- Abstract
Rationale: Brain-type natriuretic peptide (BNP) correlates with pulmonary hypertension as demonstrated by echocardiogram in congenital diaphragmatic hernia (CDH); however, its association with right ventricular (RV) function and mortality is unknown. Objectives: To characterize the relationships between echocardiogram-derived RV strain, BNP, and mortality in diaphragmatic hernia. Methods: We performed a single-center retrospective cohort study of infants with CDH and at least one BNP-echocardiogram pair within a 24-hour period. RV global longitudinal strain (GLS) and free-wall strain (FWS) were measured on existing echocardiograms. Associations among strain, BNP, and mortality were tested using mixed-effect linear and logistic regression models. Survival analysis was stratified by BNP and strain abnormalities. Results: There were 220 infants with 460 BNP-echocardiogram pairs obtained preoperatively ( n = 237), ≤1 week postoperatively ( n = 35), and >1 week postoperatively ("recovery"; n = 188). Strain improved after repair ( P < 0.0001 for all periods). Higher BNP level was associated with worse strain in recovery but not before or immediately after operation (estimate [95% confidence interval] for recovery: GLS, 1.03 [0.50-1.57]; P = 0.0003; FWS, 0.62 [0.01-1.22]; P = 0.047). BNP and strain abnormalities were associated with an extracorporeal-membrane oxygenation requirement. Higher BNP level in recovery was associated with greater mortality (odds ratio, 11.2 [1.2-571.3]; P = 0.02). Abnormal strain in recovery had high sensitivity for detection of mortality (100% for GLS; 100% for FWS) but had low specificity for detection of mortality (28% for GLS; 48% for FWS). Conclusions: Persistent RV dysfunction after CDH repair may be detected by a high BNP level and abnormal RV strain.
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- 2020
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10. Inhaled Nitric Oxide Is Associated with Improved Oxygenation in a Subpopulation of Infants with Congenital Diaphragmatic Hernia and Pulmonary Hypertension.
- Author
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Lawrence KM, Monos S, Adams S, Herkert L, Peranteau WH, Munson DA, Hopper RK, Avitabile CM, Rintoul NE, and Hedrick HL
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- Administration, Inhalation, Female, Hernias, Diaphragmatic, Congenital complications, Humans, Hypertension, Pulmonary complications, Infant, Male, Retrospective Studies, Treatment Outcome, Hernias, Diaphragmatic, Congenital drug therapy, Hypertension, Pulmonary drug therapy, Nitric Oxide administration & dosage, Oxygen metabolism
- Abstract
Objectives: To determine which patients with congenital diaphragmatic hernia (CDH) and pulmonary hypertension (PH) benefit from inhaled nitric oxide (iNO) treatment by comparing characteristics and outcomes of iNO responders to nonresponders., Study Design: We performed a retrospective chart review of infants with CDH treated at our center between 2011 and 2016. In a subset of patients, iNO was initiated for hypoxemia or echocardiographic evidence of extrapulmonary right to left shunting. Initial post-treatment blood gases were reviewed, and patients were classified as responders (increased PaO
2 >20 mm Hg) or nonresponders. Baseline characteristics, echocardiograms and outcomes were compared between groups with Fisher exact tests and Mann-Whitney t tests, as appropriate., Results: During the study period, 95 of 131 patients with CDH (73%) were treated with iNO. All patients with pretreatment echocardiograms (n = 90) had echocardiographic evidence of PH. Thirty-eight (40%) patients met treatment response criteria. Responders had significant improvements in PaO2 (51 ± 3 vs 123 ± 7 mm Hg, P < .01), alveolar-arterial gradient (422 ± 30 vs 327 ± 27 mm Hg, P < .01), and PaO2 to FiO2 ratio (82 ± 10 vs 199 ± 15 mm Hg, P < .01). Nonresponders were more likely to have left ventricular systolic dysfunction (27% vs 8%, P = .03) on echocardiogram. Responders were less likely to require extracorporeal membrane support (50 vs 24%, P = .02)., Conclusions: iNO treatment is associated with improved oxygenation and reduced need for ECMO in a subpopulation of patients with CDH with PH and normal left ventricular systolic function., (Published by Elsevier Inc.)- Published
- 2020
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11. Pathway Control in Cooperative vs. Anti-Cooperative Supramolecular Polymers.
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Herkert L, Droste J, Kartha KK, Korevaar PA, de Greef TFA, Hansen MR, and Fernández G
- Abstract
Controlling the nanoscale morphology in assemblies of π-conjugated molecules is key to developing supramolecular functional materials. Here, we report an unsymmetrically substituted amphiphilic Pt
II complex 1 that shows unique self-assembly behavior in nonpolar media, providing two competing anti-cooperative and cooperative pathways with distinct molecular arrangement (long- vs. medium-slipped, respectively) and nanoscale morphology (discs vs. fibers, respectively). With a thermodynamic model, we unravel the competition between the anti-cooperative and cooperative pathways: buffering of monomers into small-sized, anti-cooperative species affects the formation of elongated assemblies, which might open up new strategies for pathway control in self-assembly. Our findings reveal that side-chain immiscibility is an efficient method to control anti-cooperative assemblies and pathway complexity in general., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)- Published
- 2019
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12. Preventing Radiation-Induced Injury by Topical Application of an Amifostine Metabolite-Loaded Thermogel.
- Author
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Clémenson C, Liu W, Bricout D, Soyez-Herkert L, Chargari C, Mondini M, Haddad R, Wang-Zhang X, Benel L, Bloy C, and Deutsch E
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- Amifostine adverse effects, Animals, Blood Pressure drug effects, Breast Neoplasms radiotherapy, DNA Damage, Disease Models, Animal, Dogs, Drug Carriers, Female, Head and Neck Neoplasms radiotherapy, Hypotension, Orthostatic chemically induced, Mice, Mice, Inbred C57BL, Radiation Injuries, Experimental drug therapy, Radiation-Protective Agents adverse effects, Radiodermatitis drug therapy, Random Allocation, Skin Neoplasms radiotherapy, Stomatitis drug therapy, Stomatitis etiology, Amifostine administration & dosage, Gels administration & dosage, Radiation Injuries, Experimental prevention & control, Radiation-Protective Agents administration & dosage, Radiodermatitis prevention & control, Stomatitis prevention & control
- Abstract
Purpose: Despite the development of high-precision radiation therapy, ionizing radiation inevitably damages healthy tissues. Radiodermatitis and radioinduced oral mucositis are frequent and significant side effects among patients with breast and head and neck cancer, respectively. These radiation-related injuries negatively affect patient quality of life and can lead to unplanned therapeutic breaks and compromise treatment outcomes. Currently, no preventive or mitigating agent has emerged to address these issues. Although amifostine, a well-known free radical scavenger, has proven efficacy against specific radio- and chemo-induced toxicities, severe adverse side effects (reversible hypotension, nausea, emesis, etc) combined with logistical hurdles are associated with its recommended intravenous route of administration, limiting its use., Methods and Materials: We developed a thermogel containing the active thiol metabolite of amifostine (CPh-1014) that polymerizes at body temperature and serves as a matrix for topical application onto the skin or mucosa., Results: Applied before irradiation, CPh-1014 greatly reduced the severity of oral mucositis and dermatitis induced by either a single dose or fractionated irradiation regimens in in vivo mouse models. The cytoprotective effect of CPh-1014 was confirmed by the decrease in DNA double-strand breaks in the irradiated epithelium. Noticeably, CPh-1014 did not affect radiation therapy efficacy against tumors grafted at submucosal and subcutaneous sites. In contrast to the intravenous administration of amifostine, CPh-1014 oral application did not induce hypotension in dogs., Conclusions: CPh-1014 confers radioprotective effects in healthy tissues with reduced systemic side effects without compromising radiation therapy efficacy. We propose CPh-1014 as an easy-to-implement therapeutic approach to alleviate radiation therapy toxicity in patients with breast and head and neck cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2019
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13. Use of prostaglandin E1 to treat pulmonary hypertension in congenital diaphragmatic hernia.
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Lawrence KM, Berger K, Herkert L, Franciscovich C, O'Dea CLH, Waqar LN, Partridge E, Hanna BD, Peranteau WH, Avitabile CM, Hopper RK, Rintoul NE, and Hedrick HL
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- Echocardiography methods, Female, Humans, Hypertension, Pulmonary complications, Infant, Newborn, Male, Natriuretic Peptide, Brain blood, Philadelphia, Registries, Retrospective Studies, Treatment Outcome, Alprostadil therapeutic use, Hernias, Diaphragmatic, Congenital complications, Hypertension, Pulmonary drug therapy, Vasodilator Agents therapeutic use
- Abstract
Background/purpose: Prostaglandin E1 (PGE) has been used to maintain ductus arteriosus patency and unload the suprasystemic right ventricle (RV) in neonates with congenital diaphragmatic hernia (CDH) and severe pulmonary hypertension (PH). Here we evaluate the PH response in neonates with CDH and severe PH treated with PGE., Methods: We performed a retrospective chart review of CDH infants treated at our center between 2011 and 2016. In a subset, PGE was initiated for echocardiographic evidence of severe PH, metabolic acidosis, or hypoxemia. To assess PH response, we evaluated laboratory data, including B-type natriuretic peptide (BNP) and echocardiograms before and after PGE treatment. Categorical and continuous data were analyzed with Fisher's exact tests and Mann-Whitney t-tests, respectively., Results: Fifty-seven infants were treated with PGE a mean 17 ± 2 days. BNP levels declined after 1.4 ± 0.2 days of treatment and again after 5.2 ± 0.6 days. After 6 ± 0.8 days of treatment, echocardiographic estimates of severe PH by tricuspid regurgitation jet velocity, ductus arteriosus direction, and ventricular septum position also improved significantly. Treatment was not associated with postductal hypoxemia or systemic hypoperfusion., Conclusions: In patients with CDH and severe PH, PGE is well tolerated and associated with improved BNP and echocardiographic indices of PH, suggesting successful unloading of the RV., Type of Study: Treatment study., Level of Evidence: Level III., (Copyright © 2018. Published by Elsevier Inc.)
- Published
- 2019
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14. Treprostinil Improves Persistent Pulmonary Hypertension Associated with Congenital Diaphragmatic Hernia.
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Lawrence KM, Hedrick HL, Monk HM, Herkert L, Waqar LN, Hanna BD, Peranteau WH, Rintoul NE, and Hopper RK
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- Antihypertensive Agents administration & dosage, Dose-Response Relationship, Drug, Epoprostenol administration & dosage, Female, Follow-Up Studies, Humans, Hypertension, Pulmonary etiology, Hypertension, Pulmonary physiopathology, Infant, Infant, Newborn, Male, Retrospective Studies, Treatment Outcome, Epoprostenol analogs & derivatives, Hernias, Diaphragmatic, Congenital complications, Hypertension, Pulmonary drug therapy, Pulmonary Wedge Pressure drug effects, Registries
- Abstract
Objective: To evaluate the effect of continuous treprostinil in infants with severe pulmonary hypertension associated with congenital diaphragmatic hernia (CDH) on specific markers of pulmonary hypertension severity and to report the safety and tolerability of treprostinil., Study Design: We conducted a retrospective cohort study of infants with CDH-associated pulmonary hypertension treated with treprostinil from January 2011 to September 2016. Severity of pulmonary hypertension was assessed by echocardiogram and serum B-type natriuretic peptide (BNP) by using time points before initiation and 24 hours, 1 week, and 1 month after treprostinil initiation. Fisher exact tests, Wilcoxon-rank sum tests, and mixed-effects models were used for analysis., Results: Seventeen patients were treated with treprostinil for a median of 54.5 days (IQR 44.3-110 days). Compared with the concurrent CDH population (n = 147), infants treated with treprostinil were more likely to require extracorporeal support (76.5% vs 25.2%, P < .0001), to have a longer hospital stay (144 vs 60 days, P < .0001), and to need longer mechanical ventilator support (76.5 vs 30.9 days, P < .0001). Following treprostinil initiation, there was a significant reduction in BNP at 1 week (1439 vs 393 pg/mL, P < .01) and 1 month (1439 vs 242 pg/mL, P = .01). Severity of pulmonary hypertension by echocardiogram improved at 1 month (OR 0.14, CI 95% 0.04-0.48, P = .002). Despite these improvements, overall mortality remained high (35%). There were no adverse events related to treprostinil, including no hypotension, hypoxia, or thrombocytopenia., Conclusions: In this cohort, treprostinil use was associated with improved severity of pulmonary hypertension assessed by echocardiogram and decreased BNP, with no significant side effects., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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15. Protonation versus Oxonium Salt Formation: Basicity and Stability Tuning of Cyanoborate Anions.
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Kerpen C, Sprenger JA, Herkert L, Schäfer M, Bischoff LA, Zeides P, Grüne M, Bertermann R, Brede FA, Müller-Buschbaum K, Ignat'ev NV, and Finze M
- Abstract
Anhydrous H[BH
2 (CN)2 ] crystallizes from acidic aqueous solutions of the dicyanodihydridoborate anion. The formation of H[BH2 (CN)2 ] is surprising as the protonation of nitriles requires strongly acidic and anhydrous conditions but it can be rationalized based on theoretical data. In contrast, [BX(CN)3 ]- (X=H, F) gives the expected oxonium salts (H3 O)[BX(CN)3 ] while (H3 O)[BF2 (CN)2 ]/H[BF2 (CN)2 ] is unstable. H[BH2 (CN)2 ] forms chains via N-H⋅⋅⋅N bonds in the solid state and melts at 54 °C. Solutions of H[BH2 (CN)2 ] in the room-temperature ionic liquid [EMIm][BH2 (CN)2 ] contain the [(NC)H2 BCN-H⋅⋅⋅NCBH2 (CN)]- anion and are unusually stable, which enabled the study of selected spectroscopic and physical properties. [(NC)H2 BCN-H⋅⋅⋅NCBH2 (CN)]- slowly gives H2 and [(NC)H2 BCN-BH(CN)2 ]- . The latter compound is a source of the free Lewis acid BH(CN)2 , as shown by the generation of [BHF(CN)2 ]- and BH(CN)2 ⋅py., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)- Published
- 2017
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16. Right- versus left-sided congenital diaphragmatic hernia: a comparative outcomes analysis.
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Partridge EA, Peranteau WH, Herkert L, Rendon N, Smith H, Rintoul NE, Flake AW, Adzick NS, and Hedrick HL
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- Female, Hernias, Diaphragmatic, Congenital diagnosis, Hernias, Diaphragmatic, Congenital surgery, Humans, Hypertension, Pulmonary epidemiology, Incidence, Infant, Newborn, Male, Retrospective Studies, United States epidemiology, Forecasting, Hernias, Diaphragmatic, Congenital complications, Herniorrhaphy methods, Hypertension, Pulmonary complications
- Abstract
Purpose: Right-sided congenital diaphragmatic hernia (R-CDH) occurs in up to 25% of all CDH cases, but has been less widely studied compared to left-sided defects. We sought to compare characteristics and outcomes of left- versus right-sided defects in a large cohort of CDH patients who underwent standardized treatment and follow-up at a single institution., Methods: We retrospectively reviewed charts of all CDH patients in our pulmonary hypoplasia program from January 2002 through December 2014. Categorical variables were analyzed by Fisher's exact test and continuous variables by Mann-Whitney t-test (p≤0.05)., Results: A total of 330 CDH patients were treated more than the 12-year study period, with 274 (83%) left-sided and 56 (17%) right-sided cases identified. Specific pulmonary morbidities were associated with R-CDH, with increased duration of nitric oxide therapy, increased requirement for tracheostomy, increased requirement for supplemental oxygen at the time of NICU discharge, and increased chronic pulmonary hypertension with requirement for long-term Sildenafil therapy., Conclusions: In this series, R-CDH was not associated with increased mortality, but was associated with increased requirement for pulmonary vasodilatory therapy and requirement for tracheostomy. The high incidence of pulmonary complications indicates increased severity of pulmonary hypoplasia in R-CDH, supporting a role for delivery in tertiary centers with expertise in CDH management., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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17. Rate of increase of lung-to-head ratio over the course of gestation is predictive of survival in left-sided congenital diaphragmatic hernia.
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Partridge EA, Peranteau WH, Herkert L, Rintoul NE, Flake AW, Adzick NS, and Hedrick HL
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- Chi-Square Distribution, Female, Gestational Age, Head diagnostic imaging, Head embryology, Hernias, Diaphragmatic, Congenital diagnostic imaging, Humans, Lung diagnostic imaging, Lung embryology, Male, Pregnancy, Prognosis, Regression Analysis, Retrospective Studies, Severity of Illness Index, Ultrasonography, Ultrasonography, Prenatal, Head pathology, Hernias, Diaphragmatic, Congenital mortality, Hernias, Diaphragmatic, Congenital pathology, Lung pathology
- Abstract
Purpose: Congenital diaphragmatic hernia (CDH) is associated with high postnatal mortality because of pulmonary hypoplasia. The prognostic utility of serial lung-to-head circumference measurements as a marker of lung growth has not been described. Our objective was to examine the relationship between the rate of interval increase of LHR and postnatal survival in left-sided CDH., Methods: We retrospectively reviewed charts of all left-sided CDH patients from January 2004 to July 2014. All ultrasound studies performed at our institution (n=473) were reviewed. Categorical and continuous data were analyzed by chi-square and Mann-Whitney t-test, respectively, and slope analysis was performed by linear regression analysis (p<0.05)., Results: A total of 226 patients were studied, with 154 long-term survivors and 72 non-survivors. Established markers of CDH severity, including intrathoracic liver position and requirement for patch repair, were significantly increased in non-survivors (p<0.0001). The rate of LHR increase as measured by linear regression and slope analysis was significantly increased in long-term survivors (p=0.0175)., Conclusions: Our findings indicate that the interval increase in LHR levels over the course of gestation correlate with survival in left-sided CDH patients. Regular ultrasonographic re-evaluation of LHR throughout gestation following diagnosis of CDH may provide prognostic insight and help guide patient management., (Copyright © 2016. Published by Elsevier Inc.)
- Published
- 2016
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18. Systemic hypertension in giant omphalocele: An underappreciated association.
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Peranteau WH, Tharakan SJ, Partridge E, Herkert L, Rintoul NE, Flake AW, Adzick NS, and Hedrick HL
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- Antihypertensive Agents therapeutic use, Female, Hernia, Umbilical physiopathology, Hernia, Umbilical surgery, Herniorrhaphy, Humans, Hypertension drug therapy, Hypertension epidemiology, Incidence, Infant, Infant, Newborn, Male, Pennsylvania epidemiology, Retrospective Studies, Blood Pressure physiology, Hernia, Umbilical complications, Hypertension etiology
- Abstract
Purpose: To evaluate the incidence, severity and duration of systemic hypertension in infants born with giant omphalocele (GO)., Methods: A retrospective review of patients born from 2003 through 2013 with a GO or intestinal atresia (control population) and managed at a single institution was performed. The hospital course was reviewed including all blood pressures, method of omphalocele repair, requirement for antihypertensive medications and renal function., Results: Forty-five GO and 20 control patients met criteria for the study. Thirty-three GO patients underwent Schuster repair and 12 GO patients underwent delayed repair after epithelialization. Overall, 78% of GO patients had episodes of hypertension (82% Schuster and 67% delayed repair) compared to 15% of control patients (P<0.001). The majority of episodes were transient and occurred in the postoperative period (97%). Hypertension was persistent in 4 GO patients. These patients required antihypertensive medication at discharge, which was discontinued as an outpatient. No patient demonstrated significant evidence of renal abnormalities as indicated by renal ultrasound, urinalysis and/or serum creatinine level at the time of hypertension., Conclusion: Episodes of systemic hypertension are frequent in patients with GO. Episodes are often post-operative, transient and can be present in patients undergoing either a delayed or Schuster repair. A small subset of patients will have persistent hypertension requiring antihypertensive medication that can be weaned off in an outpatient setting., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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19. Neurodevelopmental outcome at one year of age in congenital diaphragmatic hernia infants not treated with extracorporeal membrane oxygenation.
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Danzer E, Gerdes M, D'Agostino JA, Bernbaum J, Hoffman C, Herkert L, Rintoul NE, Peranteau WH, Flake AW, Adzick NS, and Hedrick HL
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- Cross-Sectional Studies, Female, Hernias, Diaphragmatic, Congenital complications, Humans, Infant, Infant, Newborn, Male, Neurodevelopmental Disorders diagnosis, Neuropsychological Tests, Risk Factors, Treatment Outcome, Extracorporeal Membrane Oxygenation, Hernias, Diaphragmatic, Congenital therapy, Neurodevelopmental Disorders etiology
- Abstract
Background: We evaluated the neurodevelopmental (ND) outcome at one year of age for congenital diaphragmatic hernia (CDH) children who have not undergone extracorporeal membrane oxygenation (ECMO) treatment during the neonatal period., Material and Methods: Between 01/2005 and 06/2012, 63 consecutive CDH patients underwent ND assessment using the BSID-III at a median age of 12 months. ND delay was defined by a score of ≤ 85 in any of the composite scales. Severe impairment was defined as a score of ≤ 69 in at least one domain., Results: Mean ± SD cognitive, language, and motor functions were 94 ± 14, 86 ± 14, 90 ± 15, respectively (normal 100 ± 15, P<0.01 for each). Forty-three-percent scored within the average range for all scales. Forty-four-percent had mild, and 13% had severe delays in at least one domain. Prolonged NICU stay, intubation and O2 requirement, fundoplication, abnormal BAERs, and tracheostomy were associated with lower scores in all domains. Right-sided CDH, male gender, lower 5 min APGAR, pulmonary hypertension, and delayed start of enteral feeding were predictive of lower cognitive and/or language scores., Conclusion: At one year of age, a high percentage of CDH children whose illness did not necessitate ECMO have below normal ND scores. Modifiable and non-modifiable factors are significant determinants of adverse outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
20. Brain-type natriuretic peptide levels correlate with pulmonary hypertension and requirement for extracorporeal membrane oxygenation in congenital diaphragmatic hernia.
- Author
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Partridge EA, Hanna BD, Rintoul NE, Herkert L, Flake AW, Adzick NS, Hedrick HL, and Peranteau WH
- Subjects
- Female, Hernias, Diaphragmatic, Congenital blood, Hernias, Diaphragmatic, Congenital complications, Humans, Hypertension, Pulmonary blood, Hypertension, Pulmonary physiopathology, Infant, Newborn, Male, Monitoring, Intraoperative, Retrospective Studies, Extracorporeal Membrane Oxygenation methods, Hernias, Diaphragmatic, Congenital surgery, Herniorrhaphy, Hypertension, Pulmonary complications, Natriuretic Peptide, Brain blood, Ventricular Pressure
- Abstract
Purpose: B-type natriuretic peptide (BNP), an established biomarker of ventricular pressure overload, is used in the assessment of children with pulmonary hypertension (PH). PH is commonly observed in congenital diaphragmatic hernia (CDH). However, the use of BNP levels to guide treatment in this patient population has not been well defined. In this study, we investigate BNP levels in a large cohort of CDH patients treated at a single institution., Methods: We retrospectively reviewed charts of all CDH patients enrolled in our pulmonary hypoplasia program from 2004-2013. PH was assessed by echocardiography using defined criteria, and patients were further stratified into the following cohorts: no PH, short-term PH (requiring nitric oxide but no additional vasodilatory therapy), long-term PH (requiring continued vasodilatory therapy post-discharge), and ECMO (requiring ECMO therapy)., Results: A total of 132 patients were studied. BNP levels were significantly increased in patients with PH compared to patients with normal pulmonary pressures (P<0.01). BNP levels were not significantly different between the ST-PH, LT-PH, and ECMO cohorts, but all levels in all three cohorts were significantly increased compared to patients who did not develop PH., Conclusion: Our findings indicate that plasma BNP levels correlate with pulmonary hypertension as well as the requirement for ECMO in CDH patients. Monitoring of serial BNP levels may provide a useful prognostic tool in the management of CDH., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
21. Gold(I)-catalysed direct thioetherifications using allylic alcohols: an experimental and computational study.
- Author
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Herkert L, Green SL, Barker G, Johnson DG, Young PC, Macgregor SA, and Lee AL
- Subjects
- Catalysis, Models, Molecular, Stereoisomerism, Allyl Compounds chemistry, Gold chemistry, Propanols chemistry, Sulfides chemistry
- Abstract
A gold(I)-catalysed direct thioetherification reaction between allylic alcohols and thiols is presented. The reaction is generally highly regioselective (S(N)2'). This dehydrative allylation procedure is very mild and atom economical, producing only water as the by-product and avoiding any unnecessary waste/steps associated with installing a leaving or activating group on the substrate. Computational studies are presented to gain insight into the mechanism of the reaction. Calculations indicate that the regioselectivity is under equilibrium control and is ultimately dictated by the thermodynamic stability of the products., (© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)
- Published
- 2014
- Full Text
- View/download PDF
22. Difunctionalized {closo-1-CB11 } clusters: 1- and 2-amino-12-ethynylcarba-closo-dodecaborates.
- Author
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Hailmann M, Herkert L, Himmelspach A, and Finze M
- Abstract
Carba-closo-dodecaborate anions with two functional groups have been synthesized via a simple two-step procedure starting from monoamino-functionalized {closo-1-CB11 } clusters. Iodination at the antipodal boron atom provided access to [1-H2 N-12-I-closo-1-CB11 H10 ](-) (1 a) and [2-H2 N-12-I-closo-1-CB11 H10 ](-) (2 a), which have been transformed into the anions [1-H2 N-12-RCC-closo-1-CB11 H10 ](-) (R=H (1 b), Ph (1 c), Et3 Si (1 d)) and [2-H2 N-12-RCC-closo-1-CB11 H10 ](-) (R=H (2 b), Ph (2 c), Et3 Si (2 d)) by microwave-assisted Kumada-type cross-coupling reactions. The syntheses of the inner salts 1-Me3 N-12-RCC-closo-1-CB11 H10 (R=H (1 e), Et3 Si (1 f)) and 2-Me3 N-12-RCC-closo-1-CB11 H10 (R=H (2 e), Et3 Si (2 f)) are the first examples for a further derivatization of the new anions. All {closo-1-CB11 } clusters have been characterized by multinuclear NMR and vibrational spectroscopy as well as by mass spectrometry. The crystal structures of Cs1 a, [Et4 N]2 a, K1 b, [Et4 N]1 c, [Et4 N]2 c, 1 e, and [Et4 N][1-H2 N-2-F-12-I-closo-1-CB11 H9 ]⋅0.5 H2 O ([Et4 N]4 a⋅0.5 H2 O) have been determined. Experimental spectroscopic data and especially spectroscopic data and bond properties derived from DFT calculations provide some information on the importance of inductive and resonance-type effects for the transfer of electronic effects through the {closo-1-CB11 } cage., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2013
- Full Text
- View/download PDF
23. [Properties and biological importance of desoxyribonuclease from mammalian organs].
- Author
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SIEBERT G, LANG K, LUCIUS-LANG S, HERKERT L, STARK G, ROSSMULLER G, and JOCKEL H
- Subjects
- Animals, DNA, Deoxyribonucleases, Mammals, RNA
- Published
- 1953
- Full Text
- View/download PDF
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