Medicine and Health Sciences Commons^™

The Association Between Hospital Obstetrical Volume And Maternal Postpartum Complications, Kathy Kyser, Xin Lu, Donna Santillan, Mark Santillan, Stephen Hunter, Alison Cahill, Peter Cram

Stephen K. Hunter

OBJECTIVE: The purpose of this study was to examine the relationship between delivery volume and maternal complications. STUDY DESIGN: We used administrative data to identify women who had been admitted for childbirth in 2006. Hospitals were stratified into deciles that were based on delivery volume. We compared composite complication rates across deciles. RESULTS: We evaluated 1,683,754 childbirths in 1045 hospitals. Decile 1 and 2 hospitals had significantly higher rates of composite complications than decile 10 (11.8% and 10.1% vs 8.5%, respectively; P < .0001). Decile 9 and 10 hospitals had modestly higher composite complications as compared with decile 6 (8.8% and …

The Gamete And Embryo Compatibility Of Various Synthetic Polymers., Stephen Hunter, J. Scott, D. Hull, R. Urry

Stephen K. Hunter

Several popular and well-characterized polymeric materials were evaluated for their biocompatibility toward the cells unique to reproduction. To accomplish these studies, several in vitro tests were developed that evaluated biocompatibility between the polymers and spermatozoa, ova, and embryos. The data indicated significant differences between the materials with respect to their biocompatibility toward sperm motility, the sperm's ability to penetrate zona-free hamster eggs, and the ability of two-cell mouse embryos to divide. Polytetrafluoroethylene (PTFE-Teflon; PTFE, Chemplast Inc., Wayne, NJ), polyethylene glycol (PEG), and polyhydroxyethyl methacrylate (PHEMA) appear to be the most inert of the materials studied. Polyvinyl chloride (PVC; Tygon-Norton, Akron, …

Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter

Stephen K. Hunter

OBJECTIVE: The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria. STUDY DESIGN: Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium alginate. Timed measurements of Phe in media were performed using tandem mass spectrometry. RESULTS: Both nonencapsulated and encapsulated transiently transfected cells overexpressing PAH significantly reduced the Phe concentration in media by approximately 50% in comparison to mock-transfected cells. Cell line clones stably expressing PAH significantly …

Gene Modification Via "Plug And Socket" Gene Targeting., J. Lewis, Baoli Yang, P. Detloff, O. Smithies

Baoli Yang

No abstract provided.

A Common Human Beta Globin Splicing Mutation Modeled In Mice., J. Lewis, Baoli Yang, R. Kim, H. Sierakowska, R. Kole, O. Smithies, N. Maeda

Baoli Yang

The betaIVS-2-654 C-->T mutation accounts for approximately 20% of beta thalassemia mutations in southern China; it causes aberrant RNA splicing and leads to beta0 thalassemia. To provide an animal model for testing therapies for correcting splicing defects, we have used the "plug and socket" method of gene targeting in murine embryonic stem cells to replace the two (cis) murine adult beta globin genes with a single copy of the human betaIVS-2-654 gene. No homozygous mice survive postnatally. Heterozygous mice carrying this mutant gene produce reduced amounts of the mouse beta globin chains and no human beta globin, and have …

Appropriate Tissue- And Cell-Specific Expression Of A Single Copy Human Angiotensinogen Transgene Specifically Targeted Upstream Of The Hprt Locus By Homologous Recombination., B. Cvetkovic, Baoli Yang, R. Williamson, C. Sigmund

Baoli Yang

Development of experimental models by genetic manipulation in mice has proven to be very useful in determining the significance of particular genes in the development of or susceptibility to hypertension. Advances in molecular genetics, transgenic mouse technology, and physiological measurements in mice provided an opportunity to go a step further and develop models to analyze the physiological significance of specific gene variants potentially causing hypertension. In this report, we describe the development of a human angiotensinogen transgenic mouse model generated by targeting the human angiotensinogen gene upstream of the mouse HPRT locus by homologous recombination. The main benefit of this …

Identification Of A Tripartite Basal Promoter Which Regulates Human Terminal Deoxynucleotidyl Transferase Gene Expression., D. Bhaumik, Baoli Yang, T. Trangas, J. Bartlett, M. Coleman, D. Sorscher

Baoli Yang

In order to locate the promoter region of the human terminal deoxynucleotidyl transferase gene, serially truncated segments of the 5'-flanking region of the gene were cloned into a chloramphenicol acetyltransferase reporter vector. Transient transfection analyses of the terminal transferase-reporter gene constructs identified the basal promoter region within -34 to +40 base pairs relative to the transcription start site. Three promoter elements were defined in this region. The primary element is within 34 base pairs upstream of the transcription start site. The CAP site is 62 base pairs upstream of the translation start site. The secondary element involves sequences around the …

Regulation Of Terminal Deoxynucleotidyl Transferase Gene Expression In Mice And Men., M. Coleman, Baoli Yang, D. Sorscher

Baoli Yang

A nontemplate directed DNA polymerase, terminal deoxynucleotidyl transferase (terminal transferase) is expressed in a tissue-specific and development stage-specific manner. Its enzymatic properties and tissue localization have implicated the protein in development of normal immune function. Significant progress has been made in understanding the enzymology and important domains of this protein. More recently, studies have focused on regulation of the gene that codes for the protein in mice and humans. The murine gene has yielded to these studies more readily than the human gene. A murine basal promoter element has been identified along with several trans-acting protein factors that may regulate …

Mutational Analysis Of Residues In The Nucleotide Binding Domain Of Human Terminal Deoxynucleotidyl Transferase., Baoli Yang, K. Gathy, M. Coleman

Baoli Yang

Human terminal deoxynucleotidyl transferase (TdT) was overexpressed in a baculovirus system. The pure recombinant enzyme was identical in size, activity, kinetic constants, and metal effects to native enzyme. Three amino acids, within either the putative nucleotide binding domain and part of a DNA polymerase consensus sequence, YGDTDSLF, or a TdT consensus sequence, GGFRRGK, were altered by site-directed mutagenesis. The four mutant forms of terminal transferase were also overexpressed in the baculovirus expression system and purified from Trichoplusia ni larvae by a monoclonal antibody affinity column and compared with wild-type enzyme with respect to thermostabilities, secondary structure, metal effects, and kinetic …

The Association Between Hospital Obstetrical Volume And Maternal Postpartum Complications., Kathy L Kyser, Xin Lu, Donna Santillan, Mark Santillan, Stephen Hunter, Alison G Cahill, Peter Cram

Donna A. Santillan

OBJECTIVE: The purpose of this study was to examine the relationship between delivery volume and maternal complications.

STUDY DESIGN: We used administrative data to identify women who had been admitted for childbirth in 2006. Hospitals were stratified into deciles that were based on delivery volume. We compared composite complication rates across deciles.

RESULTS: We evaluated 1,683,754 childbirths in 1045 hospitals. Decile 1 and 2 hospitals had significantly higher rates of composite complications than decile 10 (11.8% and 10.1% vs 8.5%, respectively; P < .0001). Decile 9 and 10 hospitals had modestly higher composite complications as compared with decile 6 (8.8% and 8.5% vs 7.6%, respectively; P < .0001). Sixty percent of decile 1 and 2 hospitals were located within 25 miles of the nearest greater volume hospital.

CONCLUSION: Women who deliver at very low-volume hospitals have higher complication rates, as do women who deliver at …

Loss Of Mll Phd Finger 3 Is Necessary For Mll-Enl-Induced Hematopoietic Stem Cell Immortalization, J. Chen, Donna Santillan, M. Koonce, W. Wei, R. Luo, M. Thirman, N. Zeleznik-Le, M. Diaz

Donna A. Santillan

Reciprocal chromosomal translocations at the MLL gene locus result in expression of novel fusion proteins, such as MLL-ENL, associated with leukemia. The three PHD finger cassette, one of the highly conserved domains in MLL, is absent in all fusion proteins. This domain has been shown to interact with Cyp33, a cyclophilin which enhances the recruitment of histone deacetylases (HDAC) to the MLL repression domain and mediates HOX gene repression. Insertion of the third PHD finger of MLL into MLL-ENL allows the recruitment of Cyp33 and, subsequently, HDAC1 to the fusion protein. Furthermore, expression of the fusion protein with the PHD …

From Molecules To Medicine: A Future Cure For Preeclampsia?, Mark Santillan, Donna Santillan, Curt Sigmund, Stephen Hunter

Donna A. Santillan

In the United States, preeclampsia (PreE) affects 5-7% of all pregnancies, yet represents 15% of all maternal-fetal morbidity and mortality. PreE causes fetal growth restriction, oligohydramnios, fetal death, and maternal seizures, stroke, cerebrovascular hemorrhage and death. It has immediate and potentially long-term effects on both the fetus and mother. To date, the molecular pathogenesis of PreE is largely unknown. Multiple pathways, including dysfunctional angiogenesis, inappropriate placentation, oxidative stress and an altered immunological milieu have been proposed as key players in the development of PreE. In addition, genetic factors in all of these pathways are essential components in the etiology of …

Noninvasive Whole-Genome Sequencing Of A Human Fetus, J. Kitzman, M. Snyder, M. Ventura, A. Lewis, R. Qiu, L. Simmons, H. Gammill, C. Rubens, Donna Santillan, J. Murray, H. Tabor, M. Bamshad, E. Eichler, J. Shendure

Donna A. Santillan

Analysis of cell-free fetal DNA in maternal plasma holds promise for the development of noninvasive prenatal genetic diagnostics. Previous studies have been restricted to detection of fetal trisomies, to specific paternally inherited mutations, or to genotyping common polymorphisms using material obtained invasively, for example, through chorionic villus sampling. Here, we combine genome sequencing of two parents, genome-wide maternal haplotyping, and deep sequencing of maternal plasma DNA to noninvasively determine the genome sequence of a human fetus at 18.5 weeks of gestation. Inheritance was predicted at 2.8 x 10(6) parental heterozygous sites with 98.1% accuracy. Furthermore, 39 of 44 de novo …

Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter

Donna A. Santillan

OBJECTIVE: The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria. STUDY DESIGN: Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium alginate. Timed measurements of Phe in media were performed using tandem mass spectrometry. RESULTS: Both nonencapsulated and encapsulated transiently transfected cells overexpressing PAH significantly reduced the Phe concentration in media by approximately 50% in comparison to mock-transfected cells. Cell line clones stably expressing PAH significantly …

Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter

Mark K. Santillan

OBJECTIVE: The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria. STUDY DESIGN: Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium alginate. Timed measurements of Phe in media were performed using tandem mass spectrometry. RESULTS: Both nonencapsulated and encapsulated transiently transfected cells overexpressing PAH significantly reduced the Phe concentration in media by approximately 50% in comparison to mock-transfected cells. Cell line clones stably expressing PAH significantly …

Helping New Nurses Be Assertive About Patient Safety, S. Kinsella, K. Bigelow, S. Romano, Amy Sparks

Amy E.T. Sparks

No abstract provided.

Decreased Expression Of The Heat Shock Protein Hsp70-2 Is Associated With The Pathogenesis Of Male Infertility, H. Feng, J. Sandlow, Amy Sparks

Amy E.T. Sparks

OBJECTIVE: To examine the expression of the heat shock protein hsp70-2, and the possible relationship with the pathogenesis of male infertility. DESIGN: Prospective study. SETTING: Reproductive testing laboratory in a university hospital. PATIENT(S): Men undergoing testicular biopsy during an investigation of subfertility. INTERVENTION(S): Testicular tissues were obtained from biopsies of men undergoing infertility evaluation and subdivided into three groups: normal testes, maturational arrest and Sertoli cell-only syndrome. Immunostaining and Western blotting techniques determined expression of the heat shock protein hsp70-2 MAIN OUTCOME MEASURE(S): Expression of the heat shock protein hsp70-2 in the testes. RESULT(S): The experimental data demonstrated that the …

Semen Quality In Fertile Men In Relation To Psychosocial Stress, A. Gollenberg, F. Liu, C. Brazil, E. Drobnis, D. Guzick, J. Overstreet, J. Redmon, Amy Sparks, C. Wang, S. Swan

Amy E.T. Sparks

OBJECTIVE: To examine the association between stressful life events and semen parameters. DESIGN: Cross-sectional analysis in a pregnancy cohort study. SETTING: Prenatal clinics in five U.S. cities. PATIENT(S): Fertile men (n = 744) in the Study for Future Families, a cohort study of pregnant women and their partners. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm concentration, percent motile, and percent normal morphology and classification above/below World Health Organization (WHO) cutoffs for semen quality. RESULT(S): After adjusting for confounders, men reporting 2+ recent stressful life events had an increased risk of being classified below WHO thresholds for "normal" defined by concentration, motility, …

Serum Inhibin-B In Fertile Men Is Strongly Correlated With Low But Not High Sperm Counts: A Coordinated Study Of 1,797 European And Us Men, N. Jorgensen, F. Liu, A. Andersson, M. Vierula, D. Irvine, J. Auger, C. Brazil, E. Drobnis, T. Jensen, P. Jouannet, J. Overstreet, J. Redmon, Amy Sparks, J. Toppari, C. Wang, N. Skakkebaek, S. Swan

Amy E.T. Sparks

OBJECTIVE: To describe associations between serum inhibin-b and sperm counts, adjusted for effect of time of blood sampling, in larger cohorts than have been previously reported. DESIGN: Cross-sectional studies of spermatogenesis markers. SETTING: Four European and four US centers. PATIENT(S): Fertile men (1,797) were included and examined from October 1996-February 2005. INTERVENTION(S): The study was observational and therefore without any intervention. MAIN OUTCOME MEASURE(S): Associations between inhibin-b and semen variables controlled for time of blood sampling and other covariates. RESULT(S): Inhibin-b decreased about 2.00% per hour from 8 am-12 pm and then about 3.25% per hour from 12 pm-4 pm. …

The Clinical Benefits Of The Bladder Scanner: A Research Synthesis, Amy Sparks, D. Boyer, A. Gambrel, M. Lovett, J. Johnson, T. Richards, J. Johnson, E. Grimm, C. Daniels, S. Tylka, H. Mattingly, M. Harper, D. Palermo

Amy E.T. Sparks

No abstract provided.

Decreased Expression Of The C-Kit Receptor Is Associated With Increased Apoptosis In Subfertile Human Testes, H. Feng, J. Sandlow, Amy Sparks, A. Sandra, L. Zheng

Amy E.T. Sparks

OBJECTIVE: To examine the expression of the c-kit receptor and its ligand, stem cell factor, and their possible relation with apoptosis in infertile men. DESIGN: Prospective laboratory study. SETTING: Urology laboratory in a university hospital. PATIENT(S): Men undergoing testicular biopsy during an investigation of subfertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Expression of the c-kit receptor protein, stem cell factor, and apoptosis in the testes. RESULT(S): The c-kit receptor was strongly present in Leydig cells and type A spermatogonia of normal testes, with decreased staining in Leydig cells and type A spermatogonia of testes with maturational arrest, and staining in only …

Psychological Empowerment And Job Satisfaction Between Baby Boomer And Generation X Nurses, Amy Sparks

Amy E.T. Sparks

AIM: This paper is a report of a study of differences in nurses' generational psychological empowerment and job satisfaction. BACKGROUND: Generations differ in work styles such as autonomy, work ethics, involvement, views on leadership, and primary views on what constitutes innovation, quality, and service. METHOD: A secondary analysis was conducted from two data sets resulting in a sample of 451 registered nurses employed at five hospitals in West Virginia. One data set was gathered from a convenience sample and one from a randomly selected sample. Data were collected from 2000 to 2004. RESULTS: Baby Boomer nurses reported higher mean total …

The Effect Of Music Therapy On Patients' Perception And Manifestation Of Pain, Anxiety, And Patient Satisfaction, T. Richards, J. Johnson, Amy Sparks, H. Emerson

Amy E.T. Sparks

An extensive review and synthesis of current research was completed to identify the clinical benefit of using music therapy in the hospital setting. It demonstrated that music therapy has the potential to improve the hospital experience of patients.

One Semen Sample Or 2? Insights From A Study Of Fertile Men, A. Stokes-Riner, S. Thurston, C. Brazil, D. Guzick, F. Liu, J. Overstreet, C. Wang, Amy Sparks, J. Redmon, S. Swan

Amy E.T. Sparks

No abstract provided.

Effect Of Exogenous Testosterone On Prostate Volume, Serum And Semen Prostate Specific Antigen Levels In Healthy Young Men, C. Cooper, P. Perry, Amy Sparks, J. Macindoe, W. Yates, R. Williams

Amy E.T. Sparks

PURPOSE: We investigate and define the effects of exogenous testosterone on the normal prostate. MATERIALS AND METHODS: A total of 31 healthy volunteers 21 to 39 years old were randomized to receive either 100, 250 or 500 mg. testosterone via intramuscular injection once a week for 15 weeks. Baseline measurements of serum testosterone, free testosterone and prostate specific antigen (PSA) were taken at week 1. Semen samples were also collected for PSA content and prostate volumes were determined by transrectal ultrasound before testosterone injection. Blood was then drawn every other week before each testosterone injection for the 15 weeks, every …

Characterization Of Human Sperm Antigens Reacting With Anti-Sperm Antibodies From An Infertile Female Patient's Serum, H. Feng, Y. Han, Amy Sparks, J. Sandlow

Amy E.T. Sparks

Identification of sperm antigens that elicit immunoglobulin (Ig) production and knowledge of their roles in sperm transport and fertilization may enhance diagnosis and treatment of immunologic infertility. Sperm antigens recognized by a female patient's serum anti-sperm antibodies were characterized using an indirect immunobead-binding test, immunoblot analysis, and immunochemical labeling. The anti-sperm antibodies' effect on sperm function was evaluated by acrosome induction by calcium ionophore. Immunobeads specific for IgG were bound to the head of 79% of motile donor sperm. Immunochemical labeling of antibody-binding sites was restricted to the plasma membrane over the acrosomal crescent. No labeling was observed on the …

Social Cognition, Empathy And Functional Outcome In Schizophrenia, Amy Sparks, S. Mcdonald, B. Lino, M. O'Donnell, M. Green

Amy E.T. Sparks

Social and occupational functioning difficulties are a characteristic feature of schizophrenia, and a growing body of evidence suggests that deficits in social cognition contribute significantly to these functional impairments. The present study sought to investigate whether the association between social cognition and social functioning in schizophrenia would be mediated by self-reported levels of empathy. Thirty outpatients with a diagnosis of schizophrenia or schizoaffective disorder, and twenty-five healthy controls completed a well-validated facial affect processing task (Ekman 60-faces facial task from the Facial Expressions of Emotion - Stimuli and Tests; FEEST), The Awareness of Social Inference Test (TASIT; to assess emotion …

Imaging Of Abdominal Aortic Aneurysms, Amy Sparks, P. Johnson, M. Meyer

Amy E.T. Sparks

Given the high rate of morbidity and mortality associated with abdominal aortic aneurysms (AAAs), accurate diagnosis and preoperative evaluation are essential for improved patient outcomes. Ultrasonography is the standard method of screening and monitoring AAAs that have not ruptured. In the past, aortography was commonly used for preoperative planning in the repair of AAAs. More recently, computed tomography (CT) has largely replaced older, more invasive methods. Recent advances in CT imaging technology, such as helical CT and CT angiography, offer significant advantages over traditional CT. These methods allow for more rapid scans and can produce three-dimensional images of the AAA …

Development Of An Immunocontraceptive Vaccine. Current Status, H. Feng, J. Sandlow, Amy Sparks, A. Sandra

Amy E.T. Sparks

Development of an effective and modern contraceptive vaccine is a key factor in the global issue of regional population growth as well as agricultural, medical, economic and social development. A review was done of the current medical literature concerning development of an immunocontraceptive vaccine and relative molecular biology technology. Various approaches have been taken to identify candidate-specific antigens for immunocontraceptive development, such as sperm, zona pellucida and hormonal antigens. Suppressed fertility and the reversibility of these effects on mammalian species, including humans, have been demonstrated. The successful results obtained so far support the continued investigation for an effective immunocontraceptive vaccine.

Culture Systems: Embryo Culture And Monozygotic Twinning, Amy Sparks

Amy E.T. Sparks

The incidence of monozygotic twinning in pregnancies achieved with assisted reproductive technologies (ART) is significantly higher than spontaneously conceived pregnancies. The factors associated with ART that predispose the embryos to splitting are not well-characterized. Assisted hatching and extended embryo culture are two ART laboratory methods that have been risk factors for monozygotic twinning. The methods and strategies that may be employed to avoid monozygotic twinning are discussed in this chapter.