22 results on '"Holley SL"'
Search Results
2. History of Midwifery at Tuskegee: Vanguards of Midwifery Education.
- Author
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Holley SL, Mitchell S, Muñoz EG, and Cockerham AZ
- Subjects
- Alabama, Humans, History, 20th Century, Pregnancy, Female, Education, Nursing history, Schools, Nursing history, Midwifery education, Midwifery history, Black or African American history, Nurse Midwives education, Nurse Midwives history
- Abstract
Tuskegee, in Macon County, Alabama, has played an important role in Alabama's midwifery legacy and was home to 2 different midwifery education programs from the 1920s through the 1940s. In response to a 1918 state law requiring midwives to pass an examination to receive a practice permit in their county, stakeholders developed a four-week course for Black Alabamian midwives on the grounds of Tuskegee Institute at the John A. Andrew Memorial Hospital. In the 1940s, in the same location on the grounds of Tuskegee Institute, the Tuskegee School of Nurse-Midwifery educated Black nurse-midwives to improve Black maternal and neonatal outcomes in the South., (© 2024 The Author(s). Journal of Midwifery & Women's Health published by Wiley Periodicals LLC on behalf of American College of Nurse Midwives (ACNM).)
- Published
- 2024
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- View/download PDF
3. Malaria in Pregnancy: Considerations for Health Care Providers in Nonendemic Countries.
- Author
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Mills M, Holley SL, Coly P, and DeJoy S
- Subjects
- Female, Health Personnel, Humans, Population Surveillance, Pregnancy, Severity of Illness Index, United States, Antimalarials therapeutic use, Malaria diagnosis, Malaria drug therapy, Malaria prevention & control, Plasmodium
- Abstract
Malaria is a common infection world-wide, which carries significant risk of morbidity and mortality. Health care providers in the United States may lack experience in recognizing and treating this disease. The pathophysiology of malaria differs during pregnancy, resulting in increased risk for serious morbidity and mortality for the woman and her fetus. Screening for risk factors, especially immigration from and travel to endemic countries, is critical. Symptoms of malaria can mimic influenza-type illnesses, causing delay in diagnosis. Consultation with an infectious disease specialist and hospitalization may be required for appropriate testing and treatment. Chemoprophylaxis and counseling regarding methods to reduce risk are important components of prevention. The US Centers for Disease Control and Prevention and the World Health Organization have established protocols for treatment and are helpful resources for clinicians. A team approach to care based on the woman's stage of illness and recovery, can involve midwives, physicians, specialists and others., (© 2021 by the American College of Nurse-Midwives.)
- Published
- 2021
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4. Educating Parents on Vitamin K Prophylaxis for Newborns.
- Author
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Holley SL, Green K, Mills M, Detterman C, Rappold MF, and Thayer S
- Subjects
- Female, Humans, Infant, Newborn, Vitamin K Deficiency Bleeding nursing, Antifibrinolytic Agents therapeutic use, Chemoprevention nursing, Parents education, Vitamin K administration & dosage, Vitamin K Deficiency Bleeding prevention & control
- Abstract
Vitamin K is important in the clotting cascade, and vitamin K prophylaxis is important in preventing vitamin K deficiency bleeding (VKDB) in newborns. Breastfed newborns have been found to be particularly vulnerable to VKDB. Although oral vitamin K is available, there is no version for newborns approved by the U.S. Food and Drug Administration (FDA), and if a dose is missed, the risk of VKDB may more than double. Therefore, an injection is recommended by the American Academy of Pediatrics to prevent VKDB in newborns. Nurses often administer the newborn vitamin K injection, and they play a key role in educating parents and helping them make informed decisions about vitamin K prophylaxis for their newborns., (Copyright © 2020 AWHONN. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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5. Implementation of a Perinatal Depression Care Bundle in a Nurse-Managed Midwifery Practice.
- Author
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Gillis BD, Holley SL, Leming-Lee TS, and Parish AL
- Subjects
- Adult, Depression diagnosis, Depression psychology, Female, Humans, Midwifery instrumentation, Midwifery methods, Patient Care Bundles standards, Perinatal Care methods, Pregnancy, Pregnant People education, Pregnant People psychology, Retrospective Studies, Depression therapy, Patient Care Bundles methods
- Abstract
Objective: To implement a perinatal depression care bundle at a midwifery practice to help certified nurse-midwives (CNMs) educate women about perinatal depression and direct those affected to mental health services., Design: Quality improvement project to implement a perinatal depression care bundle for care of pregnant women between 24 and 29 weeks gestation., Setting/local Problem: CNMs practicing in a nurse-managed midwifery practice systematically screen all women for perinatal depression during pregnancy and the postpartum period but do not have a consistent method of providing anticipatory guidance about perinatal depression., Participants: All CNMs in the midwifery practice providing prenatal care (n = 16) participated in implementation., Intervention/measurements: The perinatal depression care bundle included three elements: (a) an educational handout; (b) a brief, provider-initiated discussion about perinatal depression; and (c) lists of local and online mental health resources. Four weeks after the care bundle was implemented, we conducted a retrospective chart review to assess CNMs' adherence to the new bundle., Results: Over 4 weeks, 51 prenatal visits met eligibility criteria for participation. CNMs implemented the perinatal depression care bundle for 22 (43.1%) eligible visits. CNM feedback indicated that the care bundle was brief, easy to incorporate into routine care, and well received by women., Conclusion: This project incorporated the use of a perinatal depression care bundle for women seen during routine prenatal care. Using a systematic approach to deliver perinatal depression education and resources reduces process variability and may destigmatize the illness, allowing women to feel empowered to seek help before depression symptoms become severe., (Copyright © 2019 AWHONN. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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6. A Planning Checklist for Interprofessional Consultations for Women in Midwifery Care.
- Author
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Phillippi JC, Holley SL, Thompson JL, Virostko K, and Bennett K
- Subjects
- Communication, Evaluation Studies as Topic, Female, Humans, Midwifery, Nurses, Physicians, Pregnancy, Referral and Consultation, Checklist, Continuity of Patient Care organization & administration, Maternal Health Services organization & administration, Patient Care Planning organization & administration, Patient Care Team
- Abstract
Team-based, interprofessional models of maternity care can allow women to receive personalized care based on their health needs and personal preferences. However, involvement of multiple health care providers can fragment care and increase communication errors, which are a major cause of preventable maternal morbidity and mortality. In order to improve communication within one health system, a community-engaged approach was used to develop a planning checklist for the care of women who began care with midwives but developed risks for poor perinatal outcomes. The planning checklist was constructed using feedback from women, nurses, midwives, and physicians in one interprofessional, collaborative network. In feasibility testing during 50 collaborative visits, the planning checklist provided a prompt to generate a comprehensive plan for maternity care and elucidate the rationale for interventions to women and future health care providers. In interviews after implementation of the checklist within a new collaborative format of prenatal physician consultations, women were pleased with the information received, and nurses, midwives, and physicians were positive about improved communication. This tool, developed with stakeholder input, was easy to implement and qualitatively beneficial to satisfaction and health system function. This article details the creation, implementation, and qualitative evaluation of the planning checklist. The checklist is provided and can be modified to meet the needs of other health systems., (© 2018 by the American College of Nurse-Midwives.)
- Published
- 2019
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7. Pregnancy-Associated Stroke.
- Author
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Sanders BD, Davis MG, Holley SL, and Phillippi JC
- Subjects
- Female, Humans, Pregnancy, Risk Factors, Stroke therapy, Postnatal Care, Postpartum Period, Primary Health Care, Puerperal Disorders therapy, Stroke etiology
- Abstract
Cerebrovascular accident, or stroke, is the fourth leading cause of death for all women and the eighth leading cause of pregnancy-associated death. The physiologic changes of pregnancy increase the risk of cerebrovascular accident for women. With current incidence rates, a facility with 3300 births per year can anticipate caring for one woman with a pregnancy-related stroke at least every 2 years. All maternity care providers must be able to assess women experiencing stroke-like symptoms and initiate timely care to mitigate brain tissue damage, decrease long-term morbidity, and prevent mortality. The 2 main types of stroke, ischemic and hemorrhagic, have similar presenting symptoms but very different pathophysiology and treatment. This article reviews assessment and initial treatment of pregnant and postpartum women experiencing stroke and provides guidance for subsequent maternity and primary care to assist front-line perinatal care providers who may be the first to treat affected women or may resume primary care after diagnosis., (© 2018 by the American College of Nurse-Midwives.)
- Published
- 2018
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8. Providing Evidence-Based Care During the Golden Hour.
- Author
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Neczypor JL and Holley SL
- Subjects
- Breast Feeding methods, Female, Guidelines as Topic standards, Humans, Hypoglycemia prevention & control, Hypothermia prevention & control, Infant, Newborn, Pregnancy, Umbilical Cord surgery, Evidence-Based Practice methods, Parturition, Time Factors
- Abstract
The Golden Hour encompasses a set of evidence-based practices that contribute to the physiologic stabilization of the mother-newborn dyad after birth. Important elements of the Golden Hour include delayed cord clamping, skin-to-skin contact for at least an hour, the performance of newborn assessments on the maternal abdomen, delaying non-urgent tasks (e.g., bathing the newborn) for 60 minutes, and the early initiation of breastfeeding. The Golden Hour contributes to neonatal thermoregulation, decreased stress levels in a woman and her newborn, and improved mother-newborn bonding. Implementation of these actions is further associated with increased rates and duration of breastfeeding. This article explores the evidence supporting the Golden Hour and provides strategies for successfully implementing a Golden Hour protocol on a hospital-based labor and delivery unit., (© 2017 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.)
- Published
- 2017
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9. On the same page: a novel interprofessional model of patient-centered perinatal consultation visits.
- Author
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Phillippi JC, Holley SL, Schorn MN, Lauderdale J, Roumie CL, and Bennett K
- Subjects
- Adult, Female, Humans, Patient Satisfaction, Pregnancy, Qualitative Research, Young Adult, Continuity of Patient Care organization & administration, Maternal Health Services organization & administration, Nurse Midwives organization & administration, Patient-Centered Care methods, Prenatal Care organization & administration, Professional-Patient Relations
- Abstract
Objective: To plan and implement an interprofessional collaborative care clinic for women in midwifery care needing a consultation with a maternal-fetal medicine specialist., Study Design: A community-engaged design was used to develop a new model of collaborative perinatal consultation, which was tested with 50 women. Participant perinatal outcomes and semistructured interviews with 15 women (analyzed using qualitative descriptive analysis) and clinic providers were used to evaluate the model., Results: Participant perinatal outcomes following a simultaneous consultation visit involving a nurse-midwife and maternal-fetal medicine specialist were similar to practice and hospital averages. Women's comments on their experience were positive and had the theme 'on the same page' with six subcategories: clarity, communication, collaboration, planning, validation and 'above and beyond'. Providers also were pleased with the model., Conclusion: A simultaneous consultation involving the woman, a nurse-midwife and a maternal-fetal medicine specialist improved communication and satisfaction among women and providers.
- Published
- 2016
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10. Prevention of Vitamin K Deficiency Bleeding.
- Author
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Phillippi JC, Holley SL, Morad A, and Collins MR
- Subjects
- Administration, Oral, Breast Feeding, Female, Humans, Infant, Newborn, Risk Factors, Infant, Newborn, Diseases prevention & control, Vitamin K therapeutic use, Vitamin K Deficiency Bleeding prevention & control
- Abstract
The risk that a newborn will develop vitamin K deficiency bleeding is 1700/100,000 (one out of 59) if vitamin K is not administered. When intramuscular vitamin K is administered, the risk of vitamin K deficiency bleeding is reduced to 1/100,000. While women may have misconceptions about vitamin K prophylaxis for their newborns, health care providers should be prepared with factual information. Prophylaxis is needed even for healthy newborns without risk factors for bleeding. Other forms of vitamin K supplementation, including oral administration of Food and Drug Administration-approved vitamin K preparations and maternal supplements during pregnancy or lactation, do not have the same effectiveness as the parenteral form. The formulations of vitamin K approved for use in the United States have not been associated with childhood leukemia or other childhood health problems. Care providers need to give accurate information to families regarding the risks and benefits of vitamin K prophylaxis. An interprofessional approach to education can be effective in increasing acceptance of vitamin K prophylaxis and decreasing the incidence of vitamin K deficiency bleeding. This article uses a case study approach to highlight common misconceptions about vitamin K prophylaxis and discuss a recent interprofessional collaboration to prevent vitamin K deficiency bleeding., (© 2016 by the American College of Nurse-Midwives.)
- Published
- 2016
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11. Facilitators of prenatal care in an exemplar urban clinic.
- Author
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Phillippi JC, Holley SL, Payne K, Schorn MN, and Karp SM
- Subjects
- Adolescent, Adult, Clinical Competence, Communication, Female, Humans, Interviews as Topic, Nurse Midwives, Parturition, Pregnancy, Prenatal Care organization & administration, Qualitative Research, Young Adult, Ambulatory Care Facilities organization & administration, Attitude of Health Personnel, Health Services Accessibility, Midwifery, Patient-Centered Care, Prenatal Care methods
- Abstract
Background: Perinatal outcomes have complex causes that include biologic, maternal, structural, and societal components. We studied one urban nurse-led clinic serving women at risk for poor perinatal outcomes with superior pre-term birth rates (4%) when compared with the surrounding county (11.2%)., Aim: To explore women's perspectives of their interface with the clinic, staff, and providers to understand this exemplary model., Methods: A qualitative descriptive approach with semi-structured interviews as the primary data source. Participants (n=50) were recruited from an urban clinic in the Southeast United States designed to serve women of low socio-economic status or who are recent immigrants., Findings: Women greatly valued a personal connection with the nurse-midwives and staff, and felt this resulted in high-quality care. Convenient appointment times and the lack of wait for initial or subsequent appointments made care accessible. Participants reported the relaxed and helpful approach and attitudes of the office staff were essential components of their positive experience. Women valued unrushed visits to ask questions and receive information. In addition, participants felt that clinic staff were easy to reach., Conclusion: While qualitative data cannot demonstrate causation, this study provides support that a compassionate and personalized approach to care motivates women to access needed services in pregnancy. Clinic staff are an essential component of the access process. Women overcame barriers to obtain personalized, culturally appropriate care provided by kind, competent practitioners. Clinic staff and practitioners should develop a connection with each woman by providing care that meets her physical, cultural, and personal needs., (Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2016
- Full Text
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12. Labor Dystocia: Uses of Related Nomenclature.
- Author
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Neal JL, Ryan SL, Lowe NK, Schorn MN, Buxton M, Holley SL, and Wilson-Liverman AM
- Subjects
- Cesarean Section, Female, Humans, Pregnancy, Trial of Labor, Delivery, Obstetric, Dystocia diagnosis, Labor, Obstetric, Midwifery methods, Obstetrics methods, Practice Guidelines as Topic standards, Terminology as Topic
- Abstract
Introduction: Labor dystocia (slow or difficult labor or birth) is the most commonly diagnosed aberration of labor and the most frequently documented indication for primary cesarean birth. Yet, dystocia remains a poorly specified diagnostic category, with determinations often varying widely among clinicians. The primary aims of this review are to 1) summarize definitions of active labor and dystocia, as put forth by leading professional obstetric and midwifery organizations in world regions wherein English is the majority language and 2) describe the use of dystocia and related terms in contemporary research studies., Methods: Major national midwifery and obstetric organizations from qualifying United Nations-member sovereign nations and international organizations were searched to identify guidelines providing definitions of active labor and dystocia or related terms. Research studies (2000-2013) were systematically identified via PubMed, MEDLINE, and CINAHL searches to describe the use of dystocia and related terms in contemporary scientific publications., Results: Only 6 organizational guidelines defined dystocia or related terms. Few research teams (n = 25 publications) defined dystocia-related terms with nonambiguous clinical parameters that can be applied prospectively. There is heterogeneity in the nomenclature used to describe dystocia, and when a similar term is shared between guidelines or research publications, the underlying definition of that term is sometimes inconsistent between documents., Discussion: Failure to define dystocia in evidence-based, well-described, clinically meaningful terms that are widely acceptable to and reproducible among clinicians and researchers is concerning at both national and global levels. This failure is particularly problematic in light of the major contribution of this diagnosis to primary cesarean birth rates., (© 2015 by the American College of Nurse-Midwives.)
- Published
- 2015
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13. Labor Dystocia: A Common Approach to Diagnosis.
- Author
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Neal JL, Lowe NK, Schorn MN, Holley SL, Ryan SL, Buxton M, and Wilson-Liverman AM
- Subjects
- Cesarean Section, Female, Humans, Labor, Obstetric, Oxytocin, Pregnancy, Delivery, Obstetric, Dystocia diagnosis, Labor Onset, Trial of Labor
- Abstract
Contemporary labor and birth population norms should be the basis for evaluating labor progression and determining slow progress that may benefit from intervention. The aim of this article is to present guidelines for a common, evidence-based approach for determination of active labor onset and diagnosis of labor dystocia based on a synthesis of existing professional guidelines and relevant contemporary publications. A 3-point approach for diagnosing active labor onset and classifying labor dystocia-related labor aberrations into well-defined, mutually exclusive categories that can be used clinically and validated by researchers is proposed. The approach comprises identification of 1) an objective point that strictly defines active labor onset (point of active labor determination); 2) an objective point that identifies when labor progress becomes atypical, beyond which interventions aimed at correcting labor dystocia may be justified (point of protraction diagnosis); and 3) an objective point that identifies when interventions aimed at correcting labor dystocia, if used, can first be determined to be unsuccessful, beyond which assisted vaginal or cesarean birth may be justified (earliest point of arrest diagnosis). Widespread adoption of a common approach for diagnosing labor dystocia will facilitate consistent evaluation of labor progress, improve communications between clinicians and laboring women, indicate when intervention aimed at speeding labor progress or facilitating birth may be appropriate, and allow for more efficient translation of safe and effective management strategies into clinical practice. Correct application of the diagnosis of labor dystocia may lead to a decrease in the rate of cesarean birth, decreased health care costs, and improved health of childbearing women and neonates., (© 2015 by the American College of Nurse-Midwives.)
- Published
- 2015
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14. The maternal early warning criteria: a proposal from the national partnership for maternal safety.
- Author
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Mhyre JM, D'Oria R, Hameed AB, Lappen JR, Holley SL, Hunter SK, Jones RL, King JC, and D'Alton ME
- Subjects
- Critical Illness therapy, Early Diagnosis, Female, Health Services Needs and Demand, Humans, Maternal Mortality, Patient Care Team, Population Surveillance methods, United States, Early Medical Intervention standards, Maternal Death etiology, Maternal Death prevention & control, Maternal Death statistics & numerical data, Time-to-Treatment standards
- Abstract
Case reviews of maternal death have revealed a concerning pattern of delay in recognition of hemorrhage, hypertensive crisis, sepsis, venous thromboembolism, and heart failure. Early-warning systems have been proposed to facilitate timely recognition, diagnosis, and treatment for women developing critical illness. A multidisciplinary working group convened by the National Partnership for Maternal Safety used a consensus-based approach to define The Maternal Early Warning Criteria, a list of abnormal parameters that indicate the need for urgent bedside evaluation by a clinician with the capacity to escalate care as necessary in order to pursue diagnostic and therapeutic interventions. This commentary reviews the evidence supporting the use of early-warning systems, describes The Maternal Early Warning Criteria, and provides considerations for local implementation., (© 2014 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.)
- Published
- 2014
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15. Ongoing professional practice evaluation and focused professional practice evaluation: an overview for advanced practice clinicians.
- Author
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Holley SL and Ketel C
- Subjects
- Humans, Clinical Competence standards, Health Personnel standards, Professional Practice standards
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- 2014
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16. Expanding primary care opportunities: simulation for clinical reasoning.
- Author
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Phillippi JC, Bull A, and Holley SL
- Subjects
- Competency-Based Education methods, Competency-Based Education organization & administration, Evidence-Based Practice education, Humans, Nursing Education Research, Education, Nursing, Graduate methods, Education, Nursing, Graduate organization & administration, Faculty, Nursing, Nurse Practitioners education, Primary Health Care
- Abstract
Many nurse practitioner specialties are requiring that basic primary care be included in their curricula. However, some experienced faculty within the specialty lack primary care experience. With a national shortage of nursing faculty, it is more important than ever to maximize available resources without overtaxing faculty workloads. Revision of our primary care practicum allowed nurse-midwifery faculty to lead a primary care clinical conference, using Family Nurse Practitioner (FNP) faculty as primary care experts. We revamped the clinical conference time to simulate clinical visits to guide the students through the clinical reasoning process. Low-fidelity simulation allowed students time to take a systematic approach to patient assessment, planning, and charting. The FNP "experts" were used to critique student chart notes prior to grading. This collaborative approach to the primary care clinical conference was well received by students, faculty, and preceptors and was quick and inexpensive to implement., (Copyright 2013, SLACK Incorporated.)
- Published
- 2013
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17. Polymorphisms of the cannabinoid 1 receptor gene and cognitive impairment in multiple sclerosis.
- Author
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Woolmore J, Stone M, Holley S, Jenkinson P, Ike A, Jones P, Fryer A, Strange R, Stephens R, Langdon D, and Hawkins C
- Subjects
- Adult, Cognition Disorders etiology, Female, Genotype, Homozygote, Humans, Linear Models, Linkage Disequilibrium, Male, Middle Aged, Multiple Sclerosis complications, Neuropsychological Tests, Cognition Disorders genetics, Multiple Sclerosis genetics, Polymorphism, Single Nucleotide, Receptor, Cannabinoid, CB1 genetics
- Abstract
Cognitive impairment occurs in 45-65% of multiple sclerosis (MS) patients. The cannabinoid system may potentially be neuroprotective in MS. We examined the relationship between polymorphisms of the CNR1 gene and neuropsychological outcome in MS using a test and confirmatory sample of patients. One hundred and ninety-four MS patients were assessed over five key areas of neuropsychological function, which are most commonly impaired in MS. The first 97 patients formed the test sample. A further confirmatory sample of 97 patients was used to test association found in the test sample. The schedule included: Wisconsin card sorting test 64 version, Rey auditory verbal learning task immediate and delayed scores, controlled oral word association task, judgement of line orientation and symbol digit modalities task. Three single nucleotide polymorphisms (SNPs) were typed within the CNR1 gene. For the overall neuropsychological assessment score we used a multiple linear regression model with selected covariates to show that subjects with the AA genotype of the SNP RS1049353 were more impaired (mean -2.47, SD 5.75, P = 0.008, Bonferroni corrected P = 0.024) than the other subjects (mean 0.24, SD 4.24). This was not confirmed when the association was retested in the confirmatory sample. No associations were identified between these CNR1 variants and cognitive impairment in MS.
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- 2008
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18. Differential effects of glutathione S-transferase pi (GSTP1) haplotypes on cell proliferation and apoptosis.
- Author
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Holley SL, Fryer AA, Haycock JW, Grubb SE, Strange RC, and Hoban PR
- Subjects
- Animals, Blotting, Western, Enzyme Activation, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, G1 Phase, MAP Kinase Kinase 4 metabolism, Mice, Mutagenesis, Site-Directed, NIH 3T3 Cells, Oxidative Stress, S Phase, Apoptosis, Cell Proliferation, Glutathione Transferase genetics, Haplotypes
- Abstract
Expression of the glutathione S-transferase, GSTP1, is associated with phase 1 detoxification of the products of oxidative stress. Recently, GSTP1 expression has been implicated in the regulation of cell proliferation and apoptosis through direct interaction with the c-Jun N-terminal kinase, (JNK). GSTP1 is polymorphic and allelic variants have been associated with disease susceptibility and clinical outcome. However, the influence of GSTP1 alleles on proliferation and apoptosis has not been studied previously. To investigate this, we have examined the effects of inducible expression of wild-type GSTP1*A and mutant GSTP1*C haplotypes on cell proliferation and apoptosis in NIH3T3 fibroblasts. Cells expressing GSTP1*A displayed increased doubling times and a delayed G1-S phase transition compared with cells expressing GSTP1*C. Both GSTP1*A and GSTP1*C haplotypes protected cells from undergoing apoptosis when exposed to oxidative stress. However, analysis of JNK status revealed that only GSTP1*C expression led to a reduction in JNK activity compared with GSTP1*A-expressing cells and non-induced cells. We further examined the effect of GSTP1 alleles on colony-forming efficiency (CFE) in soft agar following exposure to oxidative stress and found that GSTP1*A-expressing clones had increased CFE compared with non-induced and GSTP1*C-expressing clones. Our data suggest that GSTP1 alleles have differential effects on proliferation and apoptosis; GSTP1*A reduces cellular proliferation and protects against apoptosis through a JNK-independent mechanism. In contrast, GSTP1*C does not influence cellular proliferation but protects cells from apoptosis through JNK-mediated mechanisms.
- Published
- 2007
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19. Polymorphisms in the glutathione S-transferase mu cluster are associated with tumour progression and patient outcome in colorectal cancer.
- Author
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Holley SL, Rajagopal R, Hoban PR, Deakin M, Fawole AS, Elder JB, Elder J, Smith V, Strange RC, and Fryer AA
- Subjects
- Aged, Cohort Studies, Colorectal Neoplasms therapy, Disease-Free Survival, Female, Genotype, Glutathione S-Transferase pi metabolism, Glutathione Transferase metabolism, Humans, Isoenzymes genetics, Isoenzymes metabolism, Male, Middle Aged, Prognosis, Retrospective Studies, Treatment Outcome, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Glutathione S-Transferase pi genetics, Glutathione Transferase genetics, Polymorphism, Genetic
- Abstract
Glutathione S-transferase (GST) enzymes catalyse the detoxification of by-products of reactive oxygen species and are thus important in cellular defence mechanisms. The GSTs are polymorphic with allelic variants encoding isoforms with functional differences. GST polymorphism has been associated with susceptibility and clinical outcome in patients with cancer. In this retrospective cohort, we have investigated associations between common GSTM1, GSTM3 and GSTP1 polymorphisms with factors known to influence clinical out-come and patient survival in colorectal cancer. Significant linkage disequilibrium was demonstrated between GSTM1 and GSTM3 alleles (P< or =0.001). We identified no significant associations between the GSTP1(Ile105Val105) polymorphism and any clinical outcome parameters or patient survival. However significant associations were demonstrated with mu class GSTs. Those patients who were GSTM1 null presented less frequently with poorly-differentiated tumours (P=0.038). Furthermore, patients who were GSTM3 AA were less likely to present with advanced stage tumours (T-stage, P=0.036 and Dukes' classifications, P=0.012) or distant metastases (P=0.017) when examined alone. Upon further examination of the effect of linkage disequilibrium, we found that, in GSTM1 null individuals, GSTM3 AA (compared with other GSTM3 genotypes combined) had longer disease-free survival (HR=0.54, 95% CI 0.30-0.98, P=0.044). Thus, the GSTM3 AA genotype is associated with improved prognosis especially in those with GSTM1 null. Our findings suggest that the GST mu gene cluster mediates tumour characteristics and survival in patients with colorectal cancer.
- Published
- 2006
20. Induced expression of human CCND1 alternative transcripts in mouse Cyl-1 knockout fibroblasts highlights functional differences.
- Author
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Holley SL, Heighway J, and Hoban PR
- Subjects
- Animals, Cyclin D1 genetics, DNA biosynthesis, Disease Progression, Fibroblasts physiology, Genotype, Humans, Mice, Mice, Knockout, Mitogens pharmacology, Neoplasms genetics, Neoplasms physiopathology, Transfection, Cell Cycle genetics, Cyclin D1 biosynthesis, Polymorphism, Genetic
- Abstract
Splicing of human cyclin D1 (CCND1) mRNA producing transcripts a and b is modulated by a common polymorphism (A --> G) located in a conserved splice donor region at nucleotide 870. CCND1 A/G(870) genotype is associated with tumour progression and clinical outcome in a variety of cancers. Although in vitro expression of cyclin D1 transcript a (CCND1(tra)) has been widely investigated, few studies have examined the expression of CCND1 transcript b (CCND1(trb)). We have studied the effects of inducible expression of human CCND1(trb) in comparison with human CCND1(tra) in a mouse fibroblast knock-out for cyclin D1 (MEF(Cyl-1-/-)). Inducible expression was in stable clones isolated from MEF(Cyl-1-/-) transfectants. Induction of CCND1(tra) produced a 36-kDa protein, which led to a significant increase in the proportion of cells in S-phase, as detected by BrdU incorporation after 32 hr, compared to non-induced cells (p = 0.012). Clones induced to express CCND1(tra) exhibited a significantly increased ability to grow in serum depleted (2% FCS) medium compared to non-induced clones (p = 0.0004). Induced expression of CCND1(trb) in MEF(Cyl-1-/-) transfectants produced a 31-kDa protein and resulted in no significant difference in DNA synthesis, neither did the cells acquire the ability to grow in serum-depleted conditions compared to non-induced cells. Induction of CCND1(trb) significantly enhanced the ability of MEF(Cyl-1-/-) transfectants to form colonies in soft agar, (average 30-fold increase) compared to non-induced clones or those induced to express CCND1(tra). Our data supports the emerging view that CCND1 alternate transcripts encode proteins with differing independent biological functions. We suggest that CCND1(tra) encodes a protein involved in regulating mitogen responsive, anchorage-dependent G(1) progression, whereas CCND1(trb) modulates the ability of the cell to grow in an anchorage-independent manner., ((c) 2004 Wiley-Liss, Inc.)
- Published
- 2005
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21. Association of cyclin D1 polymorphism with increased susceptibility to oral squamous cell carcinoma.
- Author
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Holley SL, Matthias C, Jahnke V, Fryer AA, Strange RC, and Hoban PR
- Subjects
- Adult, Aged, Female, Genetic Predisposition to Disease, Humans, Logistic Models, Male, Middle Aged, Risk Factors, Smoking adverse effects, Smoking genetics, Carcinoma, Squamous Cell genetics, Cyclin D1 genetics, Mouth Neoplasms genetics, Polymorphism, Genetic
- Abstract
We have examined the association of the CCND1 A/G870 polymorphism with susceptibility and outcome in 174 German patients with oral SCC (OSCC). The CCND1 G870 allele frequency was increased in cases (G870=0.65) when compared to controls (n=155, G870=0.54) and the distribution of CCND1 genotypes were significantly different (p=0.014). Using logistic regression, correcting for age, gender and tobacco consumption, an increased frequency of the CCND1 GG870 genotype was observed in the OSCC cases (p=0.025, OR 3.37, 95% CI 1.61-9.80). No significant associations were observed between CCND1 A/G870 and tumour histological factors. Our data suggests that the CCND1 GG870 genotype is associated with increased susceptibility to OSCC. The involvement of cyclin D1 polymorphism in mechanisms of SCC development may differ in the different sub-sites of the head and neck.
- Published
- 2005
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22. Cyclin D1 polymorphism and expression in patients with squamous cell carcinoma of the head and neck.
- Author
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Holley SL, Parkes G, Matthias C, Bockmühl U, Jahnke V, Leder K, Strange RC, Fryer AA, and Hoban PR
- Subjects
- Alleles, Female, Genotype, Humans, Male, Sex Characteristics, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Cyclin D1 genetics, Cyclin D1 metabolism, Head and Neck Neoplasms genetics, Head and Neck Neoplasms metabolism, Polymorphism, Genetic
- Abstract
We have previously reported that the cyclin D1 (CCND1) GG870 genotype was associated with poorly differentiated tumors and reduced disease-free interval in patients with squamous cell carcinoma of the head and neck (SCCHN). We have now examined the association of this and a second CCND1 polymorphism with gene expression and outcome in SCCHN patients. Analysis of a CCND1 G/C1722 polymorphism revealed that CCND1 CC1722 genotype was associated with poorly differentiated tumors [P = 0.005; odds ratio (OR), 5.7; 95% CI, 1.7 to 19.2), and reduced disease-free interval (P = 0.003; Hazard Ratio (HR), 7.3; 95% CI, 1.1 to 27.2.) independently from the influence of CCND1 GG870 genotype. Patients whose tumors were negative for cyclin D1 were associated with reduced disease-free interval (P = 0.028; HR, 4.1; 95% CI, 1.4 to 14.2). Although G/C1722 genotypes were not associated with expression, we found a significant trend between reduced expression of cyclin D1 in patients with the CCND1 GG870 genotype (P = 0.04). Splicing of CCND1 mRNA in head and neck tissues was modulated by CCND1 A/G870 alleles, thus CCND1 transcript a was spliced equally from CCND1 A870 and G870 alleles, whereas CCND1 transcript b was spliced mainly from the CCND1 A870 allele. Our analysis has also identified differences in cyclin D1 genotype and protein expression and the pathogenesis of SCCHN in males and females. Thus, CCND1 CC1722 genotype was more common in female patients (P = 0.019; OR, 3.3; 95% CI, 1.3 to 10) and cyclin D1 expression was more frequent (chi-square1, 3.96; P = 0.046) and at higher levels (P = 0.004) in tumors from female patients. In summary, our data show that the two CCND1 polymorphic sites are independently associated with tumor biology and clinical outcome. CCND1 A/G870 alleles affect gene expression in head and neck tissues. We also provide preliminary evidence that the molecular genetics of SCCHN development may be influenced by patient gender.
- Published
- 2001
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