IU Indianapolis ScholarWorks :: Browsing by Author "Ingram, David A."

Browsing by Author "Ingram, David A."

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ACTUAL AND PRESCRIBED ENERGY AND PROTEIN INTAKES FOR VERY LOW BIRTH WEIGHT INFANTS: AN OBSERVATIONAL STUDY
(2012-10-11) Abel, Deborah Marie; Rickard, Karyl A.; Brady, Mary Sue; Engle, William A.; Ingram, David A.; Poindexter, Brenda B.
Objectives: To determine (1) whether prescribed and delivered energy and protein intakes during the first two weeks of life met Ziegler’s estimated requirements for Very Low Birth Weight (VLBW) infants, (2) if actual energy during the first week of life correlated with time to regain birth weight and reach full enteral nutrition (EN) defined as 100 kcal/kg/day, (3) if growth velocity from time to reach full EN to 36 weeks’ postmenstrual age (PMA) met Ziegler’s estimated fetal growth velocity (16 g/kg/day), and (4) growth outcomes at 36 weeks’ PMA. Study design: Observational study of feeding, early nutrition and early growth of 40 VLBW infants ≤ 30 weeks GA at birth in three newborn intensive care units NICUs. Results: During the first week of life, the percentages of prescribed and delivered energy (69% [65 kcal/kg/day]) and protein (89% [3.1 g/kg/day]) were significantly less than theoretical estimated requirements. Delivered intakes were 15% less than prescribed because of numerous interruptions in delivery and medical complications. During the second week, the delivered intakes of energy (90% [86 kcal/kg/day]) and protein (102% [3.5 g/kg/day]) improved although the differences between prescribed and delivered were consistently 15%. Energy but not protein intake during the first week was significantly related to time to reach full EN. Neither energy nor protein intake significantly correlated with days to return to birth weight. The average growth velocity from the age that full EN was attained to 36 weeks’ PMA (15 g/kg/day) was significantly less than the theoretical estimated fetal growth velocity (16 g/kg/day) (p<0.03). A difference of 1 g/kg/day represents a total deficit of 42 - 54 grams over the course of a month. At 36 weeks’ PMA, 53% of the VLBW infants had extrauterine growth restriction, or EUGR (<10th percentile) on the Fenton growth grid and 34% had EUGR on the Lubchenco growth grid. Conclusions: The delivered nutrient intakes were consistently less than 15% of the prescribed intakes. Growth velocity between the age when full EN was achieved and 36 weeks’ PMA was 6.7% lower than Ziegler’s estimate. One-third to one-half of the infants have EUGR at 36 weeks’ PMA.
Antenatal Determinants of Bronchopulmonary Dysplasia and Late Respiratory Disease in Preterm Infants
(American Thoracic Society, 2017-08-01) Morrow, Lindsey A.; Wagner, Brandie D.; Ingram, David A.; Poindexter, Brenda B.; Schibler, Kurt; Cotten, C. Michael; Dagle, John; Sontag, Marci K.; Mourani, Peter M.; Abman, Steven H.; Pediatrics, School of Medicine
RATIONALE: Mechanisms contributing to chronic lung disease after preterm birth are incompletely understood. OBJECTIVES: To identify antenatal risk factors associated with increased risk for bronchopulmonary dysplasia (BPD) and respiratory disease during early childhood after preterm birth, we performed a prospective, longitudinal study of 587 preterm infants with gestational age less than 34 weeks and birth weights between 500 and 1,250 g. METHODS: Data collected included perinatal information and assessments during the neonatal intensive care unit admission and longitudinal follow-up by questionnaire until 2 years of age. MEASUREMENTS AND MAIN RESULTS: After adjusting for covariates, we found that maternal smoking prior to preterm birth increased the odds of having an infant with BPD by twofold (P = 0.02). Maternal smoking was associated with prolonged mechanical ventilation and respiratory support during the neonatal intensive care unit admission. Preexisting hypertension was associated with a twofold (P = 0.04) increase in odds for BPD. Lower gestational age and birth weight z-scores were associated with BPD. Preterm infants who were exposed to maternal smoking had higher rates of late respiratory disease during childhood. Twenty-two percent of infants diagnosed with BPD and 34% of preterm infants without BPD had no clinical signs of late respiratory disease during early childhood. CONCLUSIONS: We conclude that maternal smoking and hypertension increase the odds for developing BPD after preterm birth, and that maternal smoking is strongly associated with increased odds for late respiratory morbidities during early childhood. These findings suggest that in addition to the BPD diagnosis at 36 weeks, other factors modulate late respiratory outcomes during childhood. We speculate that measures to reduce maternal smoking not only will lower the risk for preterm birth but also will improve late respiratory morbidities after preterm birth.
Assessing identity, phenotype, and fate of endothelial progenitor cells
(American Heart Association, 2008-09) Hirschi, Karen K.; Ingram, David A.; Yoder, Mervin C.; Department of Biochemistry & Molecular Biology, IU School of Medicine
From the paradigm shifting observations of Harvey, Malpighi, and van Leeuwenhoek, blood vessels have become recognized as distinct and dynamic tissue entities that merge with the heart to form a closed circulatory system.1 Vessel structures are comprised predominantly of a luminal layer of endothelial cells that is surrounded by some form of basement membrane, and mural cells (pericytes or vascular smooth muscle cells) that make up the vessel wall. In larger more complex vessel structures the vessel wall is composed of a complex interwoven matrix with nerve components. Understanding the cellular and molecular basis for the formation, remodeling, repair, and regeneration of the vasculature have been and continue to be popular areas for investigation. The endothelium has become a particularly scrutinized cell population with the recognition that these cells may play important roles in maintaining vascular homeostasis and in the pathogenesis of a variety of diseases.2 Although it has been known for several decades that some shed or extruded endothelial cells enter the circulation as apparent contaminants in the human blood stream,3 only more recent technologies have permitted the identification of not only senescent sloughed endothelial cells,4 but also endothelial progenitor cells (EPCs), which have been purported to represent a normal component of the formed elements of circulating blood5 and play roles in disease pathogenesis.6–9 Most citations refer to an article published in 1997 in which Asahara and colleagues isolated, characterized, and examined the in vivo function of putative EPCs from human peripheral blood as a major impetus for generating interest in the field.10 This seminal article presented some evidence to consider emergence of a new paradigm for the process of neovascularization in the form of postnatal vasculogenesis. Since publication of that article, interest in circulating endothelial cells, and particularly EPCs, has soared, and one merely has to type the keyword search terms, endothelial progenitor cell, to recover more than 8984 articles including 1347 review articles in PubMed (as of June 2008). What can we possibly add in the form of another EPC review that will be considered of significant value for the reader? We will attempt to review some of the early article in the field and reflect on how information in those articles was gradually derivatized into perhaps more conflicting rather than unifying concepts. We will also attempt to concisely address some of the important determinants and principles that are now leading to a new understanding of what functionally constitutes an EPC and outline some of the current measures used to identify, enumerate, and quantify these cells. Finally, we give our opinion of the best definition for an EPC based on some comparative analyses performed primarily in human subjects.
Brief report: Endothelial colony-forming cells and inflammatory monocytes in HIV
(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2015-04-15) Hays, Travis R.; Mund, Julie A.; Liu, Ziyue; Case, Jamie; Ingram, David A.; Gupta, Samir K.; Department of Medicine, IU School of Medicine
The relationships between HIV infection, monocyte activation, and endothelial colony-forming cells (ECFCs) are unknown. We compared ECFC, intermediate monocytes (CD14 CD16), and nonclassical monocytes (CD14 CD16) levels in HIV-infected participants virologically suppressed on antiretroviral therapy, HIV-infected treatment-naive participants, and HIV-uninfected healthy controls. ECFC levels were significantly higher in the HIV-infected virologically suppressed group compared with the uninfected controls. CD14 CD16 percentages (but not CD14 CD16 cells) were significantly higher in both HIV-infected groups vs. uninfected controls. In the HIV-infected groups, ECFCs and CD14 CD16 intermediate monocytes were significantly and inversely correlated. Lower availability of ECFCs may partly explain the relationship between greater intermediate monocytes and atherosclerosis in HIV.
Clinical significance of monocyte heterogeneity
(SpringerOpen, 2015-02-14) Stansfield, Brian K.; Ingram, David A.; Department of Medicine, IU School of Medicine
Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. Until recently, human monocytes were subdivided based on expression of the surface marker CD16. "Classical" monocytes express surface markers denoted as CD14(++)CD16(-) and account for greater than 70% of total monocyte count, while "non-classical" monocytes express the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition of an intermediate population identified as CD14(++)CD16(+) supports the new paradigm that monocytes are a true heterogeneous population and careful identification of specific subpopulations is necessary for understanding monocyte function in human disease. Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen. In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis.
Early administration of imatinib mesylate reduces plexiform neurofibroma tumor burden with durable results after drug discontinuation in a mouse model of neurofibromatosis type 1
(Wiley, 2020-05-27) Armstrong, Amy E.; Rhodes, Steven D.; Smith, Abbi; Chen, Shi; Bessler, Waylan; Ferguson, Michael J.; Jiang, Li; Li, Xiaohong; Yuan, Jin; Yang, Xianlin; Yang, Feng-Chun; Robertson, Kent A.; Ingram, David A.; Blakeley, Jaishri O.; Clapp, D. Wade; Pediatrics, School of Medicine
BACKGROUND Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by plexiform neurofibromas (pNF), which are thought to be congenital tumors that arise in utero and enlarge throughout life. Genetic studies in murine models delineated an indispensable role for the stem cell factor (SCF)/c-kit pathway in pNF initiation and progression. A subsequent phase 2 clinical trial using imatinib mesylate to inhibit SCF/c-kit demonstrated tumor shrinkage in a subset of pre-existing pNF, however imatinib’s role on preventing pNF development has yet to be explored. PROCEDURE We evaluated the effect of imatinib dosed at 10–100 mg/kg/day for 12 weeks to 1-month old Nf1flox/flox;PostnCre(+) mice, prior to onset of pNF formation. To determine durability of response, we then monitored for pNF growth at later time points, comparing imatinib to vehicle treated mice. We assessed gross and histopathological analysis of tumor burden. RESULTS Imatinib administered preventatively led to a significant decrease in pNF number, even at doses as low as 10 mg/kg/day. Tumor development continued to be significantly inhibited after cessation of imatinib dosed at 50 and 100 mg/kg/day. In the cohort of treated mice that underwent prolonged follow-up, the size of residual tumors was significantly reduced as compared to age-matched littermates that received vehicle control. CONCLUSIONS Early administration of imatinib inhibits pNF genesis in vivo and effects are sustained after discontinuation of therapy. These findings may guide clinical use of imatinib in young NF1 patients prior to substantial development of pNF.
Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia
(AJRCCM, 2015-01-01) Mourani, Peter M.; Sontag, Marci K.; Younoszai, Adel; Miller, Joshua I.; Kinsella, John P.; Baker, Christopher D.; Poindexter, Brenda B.; Ingram, David A.; Abman, Steven H.; Department of Pediatrics, IU School of Medicine
RATIONALE: Pulmonary hypertension (PH) is associated with poor outcomes among preterm infants with bronchopulmonary dysplasia (BPD), but whether early signs of pulmonary vascular disease are associated with the subsequent development of BPD or PH at 36 weeks post-menstrual age (PMA) is unknown. OBJECTIVES: To prospectively evaluate the relationship of early echocardiogram signs of pulmonary vascular disease in preterm infants to the subsequent development of BPD and late PH (at 36 wk PMA). METHODS: Prospectively enrolled preterm infants with birthweights 500-1,250 g underwent echocardiogram evaluations at 7 days of age (early) and 36 weeks PMA (late). Clinical and echocardiographic data were analyzed to identify early risk factors for BPD and late PH. MEASUREMENTS AND MAIN RESULTS: A total of 277 preterm infants completed echocardiogram and BPD assessments at 36 weeks PMA. The median gestational age at birth and birthweight of the infants were 27 weeks and 909 g, respectively. Early PH was identified in 42% of infants, and 14% were diagnosed with late PH. Early PH was a risk factor for increased BPD severity (relative risk, 1.12; 95% confidence interval, 1.03-1.23) and late PH (relative risk, 2.85; 95% confidence interval, 1.28-6.33). Infants with late PH had greater duration of oxygen therapy and increased mortality in the first year of life (P < 0.05). CONCLUSIONS: Early pulmonary vascular disease is associated with the development of BPD and with late PH in preterm infants. Echocardiograms at 7 days of age may be a useful tool to identify infants at high risk for BPD and PH.
Endothelial progenitor cells: identity defined?
(Wiley, 2009-01) Timmermans, Frank; Plum, Jean; Yöder, Mervin C.; Ingram, David A.; Vandekerckhove, Bart; Case, Jamie; Department of Pediatrics, IU School of Medicine
In the past decade, researchers have gained important insights on the role of bone marrow (BM)-derived cells in adult neovascularization. A subset of BM-derived cells, called endothelial progenitor cells (EPCs), has been of particular interest, as these cells were suggested to home to sites of neovascularization and neoendothelialization and differentiate into endothelial cells (ECs) in situ, a process referred to as postnatal vasculogenesis. Therefore, EPCs were proposed as a potential regenerative tool for treating human vascular disease and a possible target to restrict vessel growth in tumour pathology. However, conflicting results have been reported in the field, and the identification, characterization, and exact role of EPCs in vascular biology is still a subject of much discussion. The focus of this review is on the controversial issues in the field of EPCs which are related to the lack of a unique EPC marker, identification challenges related to the paucity of EPCs in the circulation, and the important phenotypical and functional overlap between EPCs, haematopoietic cells and mature ECs. We also discuss our recent findings on the origin of endothelial outgrowth cells (EOCs), showing that this in vitro defined EC population does not originate from circulating CD133+ cells or CD45+ haematopoietic cells.
Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial
(Elsevier, 2012-12) Robertson, Kent A.; Nalepa, Grzegorz; Yang, Feng-Chun; Bowers, Daniel C.; Ho, Chang Y.; Hutchins, Gary D.; Croop, James M.; Vik, Terry A.; Denne, Scott C.; Parada, Luis F.; Hingtgen, Cynthia M.; Walsh, Laurence E.; Yu, Menggang; Pradhan, Kamnesh R.; Edwards-Brown, Mary K.; Cohen, Mervyn D.; Fletcher, James W.; Travers, Jeffrey B.; Staser, Karl W.; Lee, Melissa W.; Sherman, Marcie R.; Davis, Cynthia J.; Miller, Lucy C.; Ingram, David A.; Clapp, D. Wade; Pediatrics, School of Medicine
BACKGROUND: Plexiform neurofibromas are slow-growing chemoradiotherapy-resistant tumours arising in patients with neurofibromatosis type 1 (NF1). Currently, there are no viable therapeutic options for patients with plexiform neurofibromas that cannot be surgically removed because of their proximity to vital body structures. We undertook an open-label phase 2 trial to test whether treatment with imatinib mesylate can decrease the volume burden of clinically significant plexiform neurofibromas in patients with NF1. METHODS: Eligible patients had to be aged 3-65 years, and to have NF1 and a clinically significant plexiform neurofibroma. Patients were treated with daily oral imatinib mesylate at 220 mg/m(2) twice a day for children and 400 mg twice a day for adults for 6 months. The primary endpoint was a 20% or more reduction in plexiform size by sequential volumetric MRI imaging. Clinical data were analysed on an intention-to-treat basis; a secondary analysis was also done for those patients able to take imatinib mesylate for 6 months. This trial is registered with ClinicalTrials.gov, number NCT01673009. FINDINGS: Six of 36 patients (17%, 95% CI 6-33), enrolled on an intention-to-treat basis, had an objective response to imatinib mesylate, with a 20% or more decrease in tumour volume. Of the 23 patients who received imatinib mesylate for at least 6 months, six (26%, 95% CI 10-48) had a 20% or more decrease in volume of one or more plexiform tumours. The most common adverse events were skin rash (five patients) and oedema with weight gain (six). More serious adverse events included reversible grade 3 neutropenia (two), grade 4 hyperglycaemia (one), and grade 4 increases in aminotransferase concentrations (one). INTERPRETATION: Imatinib mesylate could be used to treat plexiform neurofibromas in patients with NF1. A multi-institutional clinical trial is warranted to confirm these results.
Impaired compensation to femoral artery ligation in diet-induced obese mice is primarily mediated via suppression of collateral growth by Nox2 and p47phox.
(APS, 2015-10) DiStasi, Matthew R.; Mund, Julie A.; Bohlen, H. Glenn; Miller, Steven J.; Ingram, David A.; Dalsing, Michael C.; Unthank, Joseph L.; Department of Cellular and Integrative Physiology, IU School of Medicine
Novel observations in this report include the demonstration of collateral resistance as the primary limitation of hindlimb perfusion, elevated NADPH oxidase (Nox) expression in peripheral arteries, unimpaired monocyte mobilization and demargination, and reversal of suppressed principle collateral growth by Nox2 ablation/inhibition in a diet-induced obese mouse model of arterial occlusion.

Browsing by Author "Ingram, David A."

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