Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons^™

Survival Advantage Of Both Human Hepatocyte Xenografts And Genome-Edited Hepatocytes For Treatment Of Alpha-1 Antitrypsin Deficiency, Florie Borel, Qiushi Tang, Gwladys Gernoux, Cynthia Greer, Ziqiong Wang, Adi Barzel, Mark A. Kay, Leonard D. Shultz, Dale L. Greiner, Terence R. Flotte, Michael A. Brehm, Christian Mueller

Christian Mueller

Hepatocytes represent an important target for gene therapy and editing of single-gene disorders. In alpha-1 antitrypsin (AAT) deficiency, one missense mutation results in impaired secretion of AAT. In most patients, lung damage occurs due to a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In some patients, accumulation of misfolded PiZ mutant AAT protein triggers hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that correcting the Z mutant defect in hepatocytes would confer a selective advantage for repopulation of hepatocytes within an intact liver. A human PiZ allele was crossed onto an immune-deficient (NSG) strain to create …

Possible Breakdown Of Dopamine Receptor Synergism In A Mouse Model Of Huntington's Disease, Samantha F. Kennedy

University of New Orleans Theses and Dissertations

The model of basal ganglia function proposed by Albin, Young and Penney (1989) describes two anatomically independent motor pathways, the direct and indirect. However, under normal conditions striatal dopamine (DA) is required for the expression of motor behavior, and DAergic control of the two pathways (via D1 and D2 receptors, respectively) is dependent on co-activation. We tested for a possible breakdown of D1/D2 synergism using transgenic R6/1 mice bearing the human huntingtin allele (Htt). Motor stereotypy, observed prior to the onset of HD-related symptoms, was rated on a 5-point scale following activation of: A) D1 receptors alone, B) D2 receptors …

Prenatal Opioid Exposure And Intermittent Hypoxemia In Preterm Infants: A Retrospective Assessment, Elie G. Abu Jawdeh, Philip M. Westgate, Amrita Pant, Audra L. Stacy, Divya Mamilla, Aayush Gabrani, Abhijit R. Patwardhan, Henrietta S. Bada, Peter J. Giannone

Pediatrics Faculty Publications

Introduction: Intermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO₂). Preterm infants are at increased risk for IH due to their immature respiratory control/apnea of prematurity. The clinical relevance of IH is a relatively new observation with rising evidence linking IH to neonatal morbidities and long-term impairment. Hence, assessing factors that influence IH in preterm infants is imperative. Given the epidemic of opioid misuse in the USA, there is an urgent need to understand the impact of prenatal opioid exposure on neonatal outcomes. Hence, we wanted to assess the relationship between isolated prenatal opioid exposure …

Successful Reversal Of Furosemide-Induced Secondary Hyperparathyroidism With Cinacalcet., Tarak Srivastava, Shahryar Jafri, William E. Truog, Judith Sebestyen Vansickle, Winston M. Manimtim, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Secondary hyperparathyroidism (SHPT) is a rare complication of furosemide therapy that can occur in patients treated with the loop diuretic for a long period of time. We report a 6-month-old 28-weeks premature infant treated chronically with furosemide for his bronchopulmonary dysplasia, who developed hypocalcemia and severe SHPT, adversely affecting his bones. Discontinuation of the loop diuretic and the addition of supplemental calcium and calcitriol only partially reversed the SHPT, bringing serum parathyroid hormone level down from 553 to 238 pg/mL. After introduction of the calcimimetic Cinacalcet, we observed a sustained normalization of parathyroid hormone concentration at 27 to 63 pg/mL …

Plasma Brain-Derived Neurotrophic Factor Levels In Newborn Infants With Neonatal Abstinence Syndrome, Lochan Subedi, Hong Huang, Amrita Pant, Philip M. Westgate, Henrietta S. Bada, John A. Bauer, Peter J. Giannone, Thitinart Sithisarn

Pediatrics Faculty Publications

Background: Brain-derived neurotrophic factor (BDNF) is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS). Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS.

Objective: To compare …

Cost-Effectiveness Analysis Of Neonatal Screening Of Critical Congenital Heart Defects In China., Ruoyan Gai Tobe, Gerard R Martin, Fuhai Li, Akinori Moriichi, Bin Wu, Rintaro Mori

Pediatrics Faculty Publications

Background: Pulse oximetry screening is a highly accurate tool for the early detection of critical congenital heart disease (CCHD) in newborn infants. As the technique is simple, noninvasive, and inexpensive, it has potentially significant benefits for developing countries. The aim of this study is to provide information for future clinical and health policy decisions by assessing the costeffectiveness of CCHD screening in China.

Methods and Findings: We developed a cohort model to evaluate the cost-effectiveness of screening all Chinese newborns annually using 3 possible screening options compared to no intervention: pulse oximetry alone, clinical assessment alone, and pulse oximetry as …

Increased Birth Weight Is Associated With Altered Gene Expression In Neonatal Foreskin, Leryn J. Reynolds, Rebecca I. Pollack, Richard J. Charnigo, Cetewayo S. Rashid, Arnold J. Stromberg, Shu Shen, John O'Brien, Kevin J. Pearson

Pharmacology and Nutritional Sciences Faculty Publications

Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n = 7) v. the remainder of the cohort (n = 40). Multivariate linear regression models were fit to relate expression levels on differentially …

The World Database For Pediatric And Congenital Heart Surgery: The Dawn Of A New Era Of Global Communication And Quality Improvement In Congenital Heart Disease., James D St Louis, Hiromi Kurosawa, Richard A Jonas, Nestor Sandoval, Jorge Cervantes, Christo I Tchervenkov, Jeffery P Jacobs, Kisaburo Sakamoto, Giovanni Stellin, James K Kirklin

Surgery Faculty Publications

No abstract provided.

Interventions To Reduce Neonatal Mortality From Neonatal Tetanus In Low And Middle Income Countries - A Systematic Review, Adeel Ahmed Khan, Aysha Zahidie, F. Rabbani

Fauziah Rabbani

Background In 1988, WHO estimated around 787,000 newborns deaths due to neonatal tetanus. Despite few success stories majority of the Low and Middle Income Countries (LMICs) are still struggling to reduce neonatal mortality due to neonatal tetanus. We conducted a systematic review to understand the interventions that have had a substantial effect on reducing neonatal mortality rate due to neonatal tetanus in LMICs and come up with feasible recommendations for decreasing neonatal tetanus in the Pakistani setting. Methods We systemically reviewed the published literature (Pubmed and Pubget databases) to identify appropriate interventions for reducing tetanus related neonatal mortality. A total …

The Effects Of Perinatal Oxycodone Exposure On Behavioral Outcome In A Rodent Model, Thitinart Sithisarn, Sandra J. Legan, Philip M. Westgate, Melinda E. Wilson, Kristen Wellmann, Henrietta S. Bada, Susan Barron

Pediatrics Faculty Publications

Opiate addiction is now a major public health problem. Perinatal insults and exposure to opiates such as morphine in utero are well known to affect development of the hypothalamic–pituitary–adrenal axis of the offspring adversely and are associated with a higher risk of developing neurobehavioral problems. Oxycodone is now one of the most frequently abused pain killers during pregnancy; however, limited data are available regarding whether and how perinatal oxycodone exposure (POE) alters neurobehavioral outcomes of the offspring. We demonstrated that exposure to 0.5 mg/kg/day oxycodone in utero was associated with hyperactivity in adult rats in an open field. No significant …

Characterization Of Hemangioma-Initiating Stem Cells, Natalie Montwill

Electronic Thesis and Dissertation Repository

Infantile hemangioma (IH) is the most common vascular tumour of infancy. IH undergoes a unique life cycle consisting of robust endothelial cell proliferation and vessel formation in the proliferating phase, followed by spontaneous regression in the involuting phase. Our laboratory has shown that IH arises from multipotential stem cells termed hemangioma stem cells (HemSCs). However, the phenotype of HemSCs has not been fully elucidated. Here, I examined HemSCs and compared these lesion-derived cells to a panel of normal counterparts. My results show that HemSCs share similar gene expression profiles with human fetal liver-derived stem cells (FLSCs) and postnatal bone marrow …

Sustained Immune Tolerance Induction In Enzyme Replacement Therapy-Treated Crim-Negative Patients With Infantile Pompe Disease, Zoheb Kazi, Ankit Desai, K Berrier, R Troxler, R Wang, O Abdul-Rahman, P Tanpaiboon, N Mendelsohn, E Herskovitz, David Kronn, M Inbar-Feigenberg, C Ward-Melver, M Polan, P Gupta, A Rosenberg, P Kishnani

NYMC Faculty Publications

BACKGROUND: Cross-reactive immunological material-negative (CRIM-negative) infantile Pompe disease (IPD) patients develop an immune response against enzyme replacement therapy (ERT) with alglucosidase alfa that nullifies ERT efficacy. Prophylactic immune tolerance induction (ITI) with rituximab, methotrexate, and IVIG successfully prevents development of deleterious rhGAA IgG antibodies; however, safety, likelihood of success, and long-term efficacy of ITI in a larger cohort remain unknown. METHODS: Clinical data were analyzed for 19 CRIM-negative IPD patients who received ITI with rituximab, methotrexate, and IVIG in the ERT-naive setting (ERT+ITI) and compared to a historical cohort of 10 CRIM-negative IPD patients on ERT monotherapy. RESULTS: ITI was …

Risk Of Respiratory Syncytial Virus Hospitalization In The First And Second Years Of Life In Pediatric Patients With Congenital Heart Disease, Deborah Friedman, Pierre Wong

NYMC Faculty Publications

No abstract provided.

Expression Profiling Of Non-Coding Rna By Environmental Interactions In Innate Immunity, Jacob R. Longfellow

Electronic Theses and Dissertations

Cystic fibrosis (CF) is a genetic disorder that affects 30,000 people in the United States and currently has no cure. Although CF affects all of the body’s systems, it is largely characterized as a lung disease. CF is caused by a mutation in both copies of the gene for cystic fibrosis transmembrane conductance regulator (CFTR). A mutation in the CFTR gene leads to improper movement of chloride ions and water into the airways, which dysregulates the airway surface liquid volume and composition. Individuals with CF are prone to lung infections due to inefficient bacterial clearance and by the age of …

Effect Of Provision Of Home-Based Curative Health Services By Public Sector Health-Care Providers On Neonatal Survival: A Community-Based Cluster-Randomised Trial In Rural Pakistan, Sajid Bashir Soofi, Simon Cousens, Ali Turab, Yaqub Wasan, Shah Mohammed, Shabina Arif, Zaid Ahmad Bhatti, Imran Ahmed, Steve Wall, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Background : Although the effectiveness of community mobilisation and promotive care delivered by community health workers in reducing perinatal and neonatal mortality is well established, evidence in support of home-based neonatal resuscitation and infection management is mixed. We assessed the effectiveness of adding training in neonatal bag and mask resuscitation and oral antibiotic therapy for suspected neonatal infections to a basic preventive and promotive interventions package delivered by public sector community-based lady health workers (LHWs) in rural Pakistan.

Methods: We did a cluster-randomised controlled trial in two subdistricts of Naushahro Feroze in rural Sindh, Pakistan, between April 15, 2009, …

Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte

Christian Mueller

Alpha-one antitrypsin (AAT) deficiency is a genetic disease affecting the lungs due to inadequate anti-protease activity in the pulmonary interstitium. On-going human trials use intra-muscular delivery of adeno-associated virus (rAAV1), allowing expressing myofibers to secrete normal (M)AAT protein. In the Phase IIa trial, patients in the highest dose cohort (6x1012vg/kg) were given 100 intra-muscular (IM) injections of undiluted vector, with serum AAT levels still substantially below target levels. Previous work has shown that delivering rAAV vector to the musculature via limb perfusion leads to widespread gene expression in myofibers. We hypothesize that widespread delivery would result in an overall increase …

Alternative Interventions For Children Coping With Chronic Conditions: A Critical Review Of The Literature, Nina M. Pelsi, Kim S. Amer

DePaul Discoveries

Reduction of stressors and anxiety levels in adolescents with chronic illnesses is a critical concept in pediatric health care in America today. The many stressors associated with chronic illness include displaying physical and mental differences, social stigma, financial difficulty, and family stress. These stressors may affect the adolescent’s ability to learn and cope in everyday life. The current research was a critical review of the literature examining studies done with adolescents coping with chronic diseases and illnesses. The aim was to analyze the most efficacious non-pharmacological methods for reducing stressors in adolescents with chronic illness. A critical review of the …

Brain Injury With Systemic Inflammation In Newborns With Congenital Heart Disease Undergoing Heart Surgery, R Pironkova, Joseph Giamelli, H Seiden, V Parnell, D Gruber, C Sison, K Ojamaa

NYMC Faculty Publications

The potential role of systemic inflammation on brain injury in newborns with congenital heart disease (CHD) was assessed by measuring levels of central nervous system (CNS)-derived proteins in serum prior to and following cardiac surgery. A total of 23 newborns (gestational age, 39±1 weeks) with a diagnosis of CHD that required cardiac surgery with cardiopulmonary bypass (CPB) were enrolled in the current study. Serum samples were collected immediately prior to surgery and 2, 24 and 48 h following CPB, and serum levels of phosphorylated neurofilament-heavy subunit (pNF-H), neuron-specific enolase (NSE) and S100B were analyzed. Systemic inflammation was assessed by measuring …

Term Neonate With Atypical Hypoxic-Ischemic Encephalopathy Presentation: A Case Report., Nick Townley, Emily Mcnellis, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

We describe a case of atypical hypoxic-ischemic encephalopathy (HIE) in a neonate following a normal pregnancy and delivery who was found to have an umbilical vein thrombosis. The infant arrived to our center with continuous bicycling movement of her lower extremities. She had a continuous electroencephalogram that showed burst suppression and magnetic resonance imaging of the brain showed diffusely abnormal cerebral cortical/subcortical diffusion restriction which may be secondary hypoxic-ischemic injury. Interestingly, a pathology report noted a focal umbilical vein thrombosis appearing to have compressed an umbilical artery with associated arterial dissection and hematoma. Our case illustrates how umbilical venous or …

Re-Tubularization Of Highly-Ischemic Anti-Mesenteric Border (Rehab): A Novel Bowel Preservation Technique In Complex Gastroschisis., Richard J. Hendrickson, Ashwini S. Poola, Katherine W. Gonzalez, Joel Lim, Tolulope A. Oyetunji

Manuscripts, Articles, Book Chapters and Other Papers

Complex gastroschisis with bowel necrosis poses an operative challenge. Surgeons must weigh the decision between resection versus preservation of ischemic bowel. As one of the leading causes of short bowel syndrome, aggressive resection in complicated gastroschisis subjects children to prolonged dependence on parenteral nutrition and its attendant complications. Herein, we describe a novel technique aimed towards bowel preservation in complex gastroschisis patients with severe bowel ischemia with the ultimate goal for enteral autonomy.

Knowledge Base Of Adolescents With Congenital Heart Disease, Mark Gelatt, Julie Martin, Jennifer A. Marshall, Jennifer Panuco, Jenea Schmidt, Pamela Finn

Posters

Introduction:

Most congenital heart disease [CHD] is diagnosed and treated in early childhood with parents responsible for decision-making. The adolescent assumes this role in preparation for transition to an adult congenital heart program. We studied the knowledge base of our adolescent CHD patients and their parents.

Methods:

Established CHD patients, >11 y.o. and their parents, were independently surveyed in the outpatient clinic. Participation was voluntary. Cardiomyopathy, electrophysiology and transplant patients were excluded. Scores were assessed as full, partial or incomplete.

Results:

Most (98% parents; 83% adolescents) reported that their cardiologist had provided education. Adolescents provided a full (49%) and partial …

Congenital Left Ventricle-To-Coronary Sinus Fistula: A Rare Isolated Anomaly Of The Coronary Sinus., Doaa M. Aly, Nikki M. Singh, Sanket Shah

Manuscripts, Articles, Book Chapters and Other Papers

Congenital anomalies of the coronary sinus (CS) are very uncommon. They can occur either in isolation or in association with other congenital heart defects. 1 Among those anomalies, congenital fistulae connecting the left ventricle and the CS represent a very rare entity. Most reported cases of CS fistula generally originate in the right coronary artery or left anterior descending coronary artery system. 2 We describe an extremely rare case of an isolated high-pressure congenital left ventricle–to–CS fistula as an anomaly of the CS in an otherwise asymptomatic child. The initial clinical presentation and follow-up, imaging studies, and plan for management …

Abnormal Dendritic Maturation Of Developing Cortical Neurons Exposed To Corticotropin Releasing Hormone (Crh): Insights Into Effects Of Prenatal Adversity?, Megan M. Curran, Curt A. Sandman, Elyssia Poggi Davis, Laura M. Glynn, Tallie Z. Baram

Psychology Faculty Articles and Research

Corticotropin releasing hormone (CRH) produced by the hypothalamus initiates the hypothalamic- pituitary-adrenal (HPA) axis, which regulates the body's stress response. CRH levels typically are undetectable in human plasma, but during pregnancy the primate placenta synthesizes and releases large amounts of CRH into both maternal and fetal circulations. Notably, placental CRH synthesis increases in response to maternal stress signals. There is evidence that human fetal exposure to high concentrations of placental CRH is associated with behavioral consequences during infancy and into childhood, however the direct effects on of the peptide on the human brain are unknown. In this study, we used …

Validating Candidate Congenital Heart Disease Genes In Drosophila., Jun-Yi Zhu, Yulong Fu, Adam Richman, Zhe Han

Pediatrics Faculty Publications

Genomic sequencing efforts can implicate large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system to validate candidate gene association with pathology is therefore useful. We present such a system employing Drosophila to validate candidate congenital heart disease (CHD) genes. The protocols exploit comprehensive libraries of UAS-GeneX-RNAi fly strains that when crossed into a 4×Hand-Gal4 genetic background afford highly efficient cardiac-specific knockdown of endogenous fly orthologs of human genes. A panel of quantitative assays evaluates phenotypic severity across multiple cardiac parameters. These include developmental lethality, larva and adult heart morphology, …

5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte

Christian Mueller

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2.5% of the target level from …

Zika 2016: A 3-Phase Longitudinal Study Of The Media Impact On Public Attitudes And Behavioral Response Characteristics, Karly Kownslar

Electronic Theses & Dissertations

Using the Extended Parallel Processing Model (EPPM) as a theoretical framework, the present 3-phase longitudinal study examines the impact of media exposure to Zika information on public perception of the threat severity, personal susceptibility, and behavioral intentions toward the threat of Zika virus between May and November of 2016. A total of 826 participants took an online survey throughout three phases, roughly one month apart. Participants were recruited using Amazon Mechanical Turk and TurkPrime. Measured EPPM concepts include: perceived severity, susceptibility, self- efficacy, response-efficacy, third-person effects, combined with behavioral intentions. Participants also selected the sources from which they …

Audiology Students’ Perception Of Hybrid Simulation Experiences: Qualitative Evaluation Of Debriefing Sessions, Ahmad A. Alanazi, Nannette Nicholson, Samuel R. Atcherson, Clifford A. Franklin, Naveen K. Nagaraj, Michael Anders, Laura Smith-Olinde

Journal of Early Hearing Detection and Intervention

Simulation-based research is still new in the audiology field and requires more research to better understand students’ perspectives on standardized patients/parents (SPs) and manikins use. There is also limited research about debriefing practices in audiology. This qualitative study used a baby simulator and SPs to evaluate audiology students’ reflection during three debriefing sessions conducted at the University of Arkansas for Medical Science (UAMS) Simulation Center. Seventeen Doctor of Audiology (AuD) students participated in the simulation event, and the data were collected using the transcripts of videotaped debriefing sessions. The qualitative content analysis of the transcripts revealed eight sub-themes: support, compassion, …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

A Description Of The Methods Of The Aspirin Supplementation For Pregnancy Indicated Risk Reduction In Nulliparas (Aspirin) Study, Matthew K. Hoffman, Shivaprasad S. Goudar, Bhalachandra S. Kodkany, Norman Goco, Marion Koso-Thomas, Menachem Miodovnik, Elizabeth M. Mcclure, Dennis D. Wallace, Jennifer J. Emingway-Foday, Antoinette Tshefu, Adrien Lokangaka, Carl L. Bose, Elwyn Chomba, Musaku Mwenechanya, Waldemar A. Carlo, Ana Garces, Nancy F. Krebs, K. Michael Hambidge, Sarah Saleem, Robert L. Goldenberg, Archana Patel, Patricia L. Hibberd, Fabian Esamai, Edward A. Liechty, Robert Silver, Richard J. Derman

Community Health Sciences

Background: Preterm birth (PTB) remains the leading cause of neonatal mortality and long term disability throughout the world. Though complex in its origins, a growing body of evidence suggests that first trimester administration of low dose aspirin (LDA) may substantially reduce the rate of PTB.
Methods: Hypothesis: LDA initiated in the first trimester reduces the risk of preterm birth. Study Design Type: Prospective randomized, placebo-controlled, double-blinded multi-national clinical trial conducted in seven low and middle income countries. Trial will be individually randomized with one-to-one ratio (intervention/control) Population: Nulliparous women between the ages of 14 and 40, with a …

Role Of Biomechanical Forces In Hyperfiltration-Mediated Glomerular Injury In Congenital Anomalies Of The Kidney And Urinary Tract., Tarak Srivastava, Ganesh Thiagarajan, Uri S. Alon, Ram Sharma, Ashraf El-Meanawy, Ellen T. Mccarthy, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Congenital anomalies of the kidney and urinary tract (CAKUT) including solitary kidney constitute the main cause of progressive chronic kidney disease (CKD) in children. Children born with CAKUT develop signs of CKD only during adolescence and do not respond to renin-angiotensin-aldosterone system blockers. Early cellular changes underlying CKD progression to end-stage renal disease by early adulthood are not well understood. The mechanism of maladaptive hyperfiltration that occurs from loss of functional nephrons, including solitary kidney, is not clear. We re-examine the phenomenon of hyperfiltration in the context of biomechanical forces with special reference to glomerular podocytes. Capillary stretch exerts tensile …