21 results on '"Raker C"'
Search Results
2. The Habitats and Biodiversity of Watamu Marine National Park: Evaluating Our Knowledge of One of East Africa's Oldest Marine Protected Areas
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Cowburn, B., primary, Musembi, P.M., additional, Sindorf, V., additional, Kohlmeier, D., additional, Raker, C., additional, Nussbaumer, A., additional, Hereward, H.F.R., additional, Van Baelenberghe, B., additional, Goebbels, D., additional, Kamire, J., additional, Horions, M., additional, Sluka, R.D., additional, Taylor, M.L., additional, and Rogers, A.D., additional
- Published
- 2018
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3. Abstract P6-12-25: Sexual function in breast cancer survivors stratified by adjuvant therapies and surgical modalities
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Gandhi, C, primary, Butler, EC, additional, Pesek, S, additional, Kwait, R, additional, Clark, M, additional, Raker, C, additional, Stuckey, A, additional, and Gass, J, additional
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- 2018
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4. Pregnancy and fetal outcomes of symptoms of sleep-disordered breathing
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Bourjeily, G., primary, Raker, C. A., additional, Chalhoub, M., additional, and Miller, M. A., additional
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- 2010
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5. Misoprostol for the non-viable first trimester pregnancies – can patients accurately determine spontaneous miscarriage completion?
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Carey, M., primary, Masterton, D., additional, Matteson, K., additional, and Raker, C., additional
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- 2009
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6. Saquinavir-mediated inhibition of human immunodeficiency virus (HIV) infection in SCID mice implanted with human fetal thymus and liver tissue: an in vivo model for evaluating the effect of drug therapy on HIV infection in lymphoid tissues
- Author
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Pettoello-Mantovani, M, primary, Kollmann, T R, additional, Raker, C, additional, Kim, A, additional, Yurasov, S, additional, Tudor, R, additional, Wiltshire, H, additional, and Goldstein, H, additional
- Published
- 1997
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- View/download PDF
7. Pregnancy Outcomes from a Multidisciplinary Obstetric-Medicine/Rheumatology Clinic in the United States: A Five-Year Retrospective Analysis.
- Author
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Reed G, Deeb M, Mathew J, Rigby K, Cravens E, Raker C, Jafari-Esfahani S, Reginato AM, Tarabulsi G, and Cunha JS
- Abstract
Objectives: At Women & Infants Hospital in Providence, Rhode Island, the Specialty Care in Pregnancy clinic combines obstetric-medicine internists with rheumatologists to care for pregnant women with rheumatologic conditions. These clinics are scarce, with only three known similar clinics in the United States. This study aims to characterize the population cared for in this clinic, identify interventions, and analyze pregnancy outcomes for the mothers and newborns., Methods: A five-year retrospective chart review was performed from January 1
st , 2016, through December 31st , 2021., Results: Of 81 patients, 62% had a clinically diagnosed rheumatic disorder. Of 87 patient visits, which included preconception, prenatal and postpartum encounters, 54% were on conventional synthetic disease modifying antirheumatic drugs and 17% were on biologic disease modifying antirheumatic drugs. New medications were started in 52% of patients. 52% of pregnancies resulted in live births with 2% resulting in miscarriages. Prematurity occurred in 19% of newborns, and 9% had intrauterine growth restriction., Conclusion: Our study illustrates the benefits of multidisciplinary care in patients with rheumatologic disorders during their prenatal and perinatal periods. The expertise from both the obstetric-medicine internists and rheumatologists was critical in making complex decisions that weigh the benefits of therapy against potential risks for the fetus. Our multidisciplinary approach resulted in doubling of the number of patients on disease modifying therapy and increased prophylaxis with hydroxychloroquine and/or aspirin therapy as recommended by current guidelines. Additional multidisciplinary clinics of this type would help coordinate care between physicians that frequently treat these high-risk, unique patients and open the door for more research of this understudied population., (This article is protected by copyright. All rights reserved.)- Published
- 2024
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8. Unexpected Medical Conditions Discovered During Live Donor Kidney Evaluation: Single Center Study.
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Lee A, Bayliss G, Osband A, Morrissey P, Gohh R, Raker C, and Merhi B
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- Humans, Living Donors, Retrospective Studies, Kidney, Kidney Transplantation, Kidney Failure, Chronic epidemiology, Kidney Failure, Chronic surgery
- Abstract
Objectives: Living donor kidney transplantation (LDKT) is the preferred method of treatment for patients with end-stage kidney disease. Potential living kidney donors (PLKD) are evaluated through a thorough medical, psychological and surgical work-up to ensure successful transplantation with minimal risks to all parties involved. The transplant center at Rhode Island Hospital has noticed an increasing number of PLKDs excluded from donation due to conditions newly diagnosed during the screening process. Our objective is to understand the local trends underlying the high PLKD exclusion rates in the context of newly diagnosed conditions, age, race, and sex of the excluded donors., Study Design and Methods: Our study is a retrospective electronic medical record review of the 429 PLKDs screened at Rhode Island Hospital Kidney Transplant Center between December 2012 and April 2023. Age, race, gender, relationship to recipient, and reasons for exclusion were collected from the medical record for each PLKD., Conclusion: 115 of the 429 total PLKDs screened were excluded for newly diagnosed conditions, the most common of which were renal issues (49%), diabetes mellitus (33%), and hypertension (13%), with many comorbid diagnoses. While these donors were able to receive proper treatment after their diagnosis, the earliest intervention possible yields the best prognosis. The high prevalence of treatable yet undiagnosed conditions raise many public health concerns, such as primary care gaps or discontinuous healthcare, and increases awareness about the importance of follow-up care for the excluded PLKDs.
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- 2024
9. Maternal education and its association with maternal and neonatal adverse outcomes in live births conceived using medically assisted reproduction (MAR).
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Hobbs CL, Raker C, Jude G, Eaton JL, and Wagner S
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Background: To examine the association between maternal education and adverse maternal and neonatal outcomes in women who conceived using medically assisted reproduction, which included fertility medications, intrauterine insemination, or in vitro fertilization., Methods: We conducted a retrospective cohort study utilizing the US Vital Statistics data set on national birth certificates from 2016 to 2020. Women with live, non-anomalous singletons who conceived using MAR and had education status of the birthing female partner recorded were included. Patients were stratified into two groups: bachelor's degree or higher, or less than a bachelor's degree. The primary outcome was a composite of maternal adverse outcomes: intensive care unit (ICU) admission, uterine rupture, unplanned hysterectomy, or blood transfusion. The secondary outcome was a composite of neonatal adverse outcomes: neonatal ICU admission, ventilator support, or seizure. Multivariable modified Poisson regression models with robust error variance adjusted for maternal age, race, marital status, prenatal care, smoking during pregnancy, neonatal sex, and birth year estimated the relative risk (RR) of outcomes with a 95% confidence interval (CI)., Results: 190,444 patients met the inclusion criteria: 142,943 had a bachelor's degree or higher and 47,501 were without a bachelor's degree. Composite maternal adverse outcomes were similar among patients with a bachelor's degree (10.1 per 1,000 live births) and those without a bachelor's degree (9.4 per 1,000 live births); ARR 1.05, 95% CI (0.94-1.17). However, composite adverse neonatal outcomes were significantly lower in women with a bachelor's degree or higher (94.1 per 1,000 live births) compared to women without a bachelor's degree (105.9 per 1,000 live births); ARR 0.91, 95% CI (0.88-0.94)., Conclusions: Our study demonstrated that lower maternal education level was not associated with maternal adverse outcomes in patients who conceived using MAR but was associated with increased rates of neonatal adverse outcomes. As access to infertility care increases, patients who conceive with MAR may be counseled that education level is not associated with maternal morbidity. Further research into the association between maternal education level and neonatal morbidity is indicated., (© 2023. The Author(s).)
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- 2023
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10. Survey of young women with breast cancer to identify rates of fertility preservation (FP) discussion and barriers to FP care.
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Sauerbrun-Cutler MT, Pandya S, Recabo O, Raker C, Clark MA, and Robison K
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- Humans, Female, Cross-Sectional Studies, Neoplasm Recurrence, Local, Cryopreservation, Counseling, Fertility Preservation methods, Neoplasms therapy, Infertility, Breast Neoplasms epidemiology, Breast Neoplasms drug therapy
- Abstract
Purpose: To identify the proportion of reproductive age women with breast cancer that engaged in a fertility preservation discussion and reproductive endocrinology and infertility (REI) consultation., Methods: This cross-sectional survey recruited women 18-42 years who were diagnosed with breast cancer from 2006 to 2016 by phone or email and asked them to complete an online survey. Demographic characteristics, barriers to FP, utilization of FP consultation, and FP procedures (oocyte and embryo cryopreservation) were analyzed., Results: A majority of women (64%) did not have FP discussed by any provider. Older women and those who were parents at the time of diagnosis were less likely to engage in a FP discussion. However, there were no significant differences in partner status or cancer stage between women with or without FP discussions. Of the women who desired future children prior to the cancer diagnosis, 93% received chemotherapy; however, only 34% of these women had a consultation with an REI. The most common reasons for declining FP consultation were already having their desired number of children (41%), financial barriers (14%), and concern about delaying cancer treatment and cancer recurrence (12%). Forty percent of women who desired future children and met with an REI pursued FP procedures., Conclusion: Younger women were more likely to receive FP counseling. FP consultations and procedures were low even in women who desired future fertility, with the predominant barriers being cost, fears concerning a delay in cancer treatment, and future cancer recurrence., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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11. Comparing Effectiveness of Remote-learning Formats for Resident Physician Didactics.
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Shinnick JK, Narvaez JL, Raker C, and Brousseau EC
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- Humans, Curriculum, Internship and Residency, Education, Medical, Physicians
- Abstract
Background: It is important to investigate remote- learning options for medical education. We evaluated retention of research-related knowledge after exposure to pre-recorded audio-based didactics (AUDIO) versus video conference-based didactics (ZOOM)., Methods: Obstetrics and Gynecology residents over the 2020-2021 academic year were randomized to didactics delivered in AUDIO versus ZOOM formats. At baseline, immediately post-exposure, and 3-month post-exposure, objective knowledge was assessed through 15 multiple choice questions. Confidence and satisfaction were assessed on a 5-point Likert scale. Median differences and 95% confidence intervals (CI) were applied to identify a 10% non-inferiority margin., Results: Thirty of thirty-one (30/31, 96.8%) eligible residents participated. At 3-month post-exposure, AUDIO was non-inferior to ZOOM (6.3% mean difference in knowledge scores, 95% CI -3.5-16.2). There were no differences in satisfaction or confidence, though a greater proportion of AUDIO participants indicated they would use a similar resource independently (p=0.008)., Conclusion: AUDIO didactics may be non-inferior to ZOOM.
- Published
- 2023
12. Factors associated with disparate outcomes among Black women undergoing in vitro fertilization.
- Author
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Ghidei L, Wiltshire A, Raker C, Ayyar A, and Brayboy LM
- Abstract
Objective: To determine if Black women have worse in vitro fertilization (IVF) outcomes than women of other races/ethnicities, and to establish which factors are associated with the IVF outcomes of Black women., Design: Retrospective cohort study., Setting: Not applicable., Patients: All patients undergoing IVF., Interventions: Not applicable., Main Outcome Measures: Spontaneous abortion rate, clinical pregnancy rate, and live birth rate., Results: A total of 71,389 patient cycles were analyzed. Of the 40,545 patients who were included, 6.4% of patients were Black, 62% were White, 7.3% were Hispanic/Latino, and 15% were Asian. After IVF, Black women had significantly more miscarriages than White but not Hispanic or Asian patients (8.0% Black vs. 6.9% White, 7.4% Hispanic, and 7.5% Asian). Clinical pregnancy rates were significantly lower for Black women compared with all other races (45% Black vs. 52% White, 52% Hispanic, and 53% Asian). The odds ratio (OR) of live birth from all cycles were 30% less than that for White women (OR, 1.00 Black vs. 1.43 White) and 22% less than that for Hispanic women (OR, 1.00 Black vs. 1.29 Hispanic). This statistically significant difference in the live birth rate persisted even after adjusting for patient characteristics (OR, 1.00 Black vs. 1.32 White, 1.23 Hispanic, and 1.18 Asian)., Conclusions: Black women have worse IVF outcomes than women of all other racial backgrounds undergoing IVF. The factors associated with the disparate outcomes of Black women undergoing IVF outcomes include older age starting IVF, higher body mass index, tubal factor infertility, and diabetes., (© 2021 Published by Elsevier Inc. on behalf of American Society for Reproductive Medicine.)
- Published
- 2021
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13. Molecular markers in uterine serous cancer: Correlation between endometrial biopsy and hysterectomy specimens.
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Lokich E, Kole M, Raker C, Quddus MR, and Mathews C
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Objectives: To measure the correlation of molecular biomarkers between biopsy and final pathology specimens in uterine serous cancer (USC) and to establish the overall prevalence of specific biomarkers among subjects with USC., Methods: Twenty eight patients with a diagnosis of USC and sufficient biopsy and hysterectomy specimens were identified. IHC was used to measure the biomarker status of EGFR, phospho-AKT, ER, PR, Her2/neu, and PTEN in FFPE tissue. The presence or absence of individual biomarkers was then compared between a given subject's diagnostic biopsy specimen and final hysterectomy specimen., Results: In the cohort identified, average age was 72 and average BMI was 29. 75% of patients had full lymphadenectomy performed. The average time from biopsy to surgery was 33 days (range 9-91 days). The distribution of disease was 61% stage I (n = 17), 14% stage II (n = 4), 22% stage III (n = 6) and 4% stage IV (n = 1). Biopsy and hysterectomy specimens agreed 67% of the time for phospho-AKT, 80% for ER, 73% for PR, 83% for EGFR, 100% for Her2/neu and 95% for PTEN loss., Conclusions: The measurement of specific biomarkers correlated well between subjects' biopsy and hysterectomy specimens in women with USC as measured by a pathologist using routine clinical techniques. Preoperative diagnostic biopsy may be a useful tool for guiding neoadjuvant targeted therapy in USC.
- Published
- 2019
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14. Project ESCUCHE: A Spanish-language Radio-based Intervention to Increase Science Literacy.
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Phipps MG, Venkatesh KK, Ware C, Lightfoot M, Raker C, and Rodriguez P
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- Adolescent, Adult, Female, Humans, Language, Male, Middle Aged, Rhode Island, Young Adult, Health Literacy, Hispanic or Latino statistics & numerical data, Radio
- Abstract
Project ESCUCHE was developed to evaluate the potential to increase science literacy among Spanish-language radio listeners. In collaboration with community partners, we developed a 10-week culturally applicable science and health curriculum delivered through Spanish-language radio. Science literacy was assessed before and after the intervention. Among the 51 participants, 70% were female, 76% were > 35 years old, 60% reported some college education, and 90% preferred speaking in Spanish versus English. The majority of participants (>94%) demonstrated adequate baseline functional health literacy, and 70% reported listening to all ten of the radio programs. Participants demonstrated significant increases in science knowledge post intervention (mean score before intervention 68.4% and after intervention 77%). This improvement was consistent across gender, education level, age, and baseline functional health literacy. Radio has the potential to be an effective method of engaging the Spanish-speaking community to improve science literacy. The results from the ESCUCHE program add to the groundwork for further exploration of how radio programming and other media platforms can be used to impact health.
- Published
- 2018
15. Levels of antimüllerian hormone in serum during the normal menstrual cycle.
- Author
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Lambert-Messerlian G, Plante B, Eklund EE, Raker C, and Moore RG
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- Adolescent, Adult, Age Factors, Body Mass Index, Female, Follicular Phase blood, Humans, Immunoassay, Luteal Phase blood, Middle Aged, Prospective Studies, Smoking blood, Time Factors, Young Adult, Anti-Mullerian Hormone blood, Menstrual Cycle blood
- Abstract
Objective: To determine whether levels of antimüllerian hormone (AMH) in serum vary during the normal menstrual cycle, using the most recently developed immunoassay method., Design: Prospective cohort study., Setting: Local community., Patient(s): Women with normal menstrual cycles and between the ages of 18 and 45 years were recruited (n = 45). Blood samples were collected on 5 days within each cycle: two in the follicular phase and three after confirmed ovulation. Exclusion criteria were anovulatory cycles, incomplete sample collection, insufficient blood volume, or non-Caucasian ethnicity., Intervention(s): None., Main Outcome Measure(s): Serum samples were tested for levels of AMH using a new immunoassay method (Ansh Labs). The effects of body mass index (BMI) and smoking on serum AMH levels were considered., Result(s): Serum AMH levels varied significantly during the menstrual cycle, with the highest levels in the follicular phase. When the analysis was stratified by age, AMH variation during the menstrual cycle was significant only for women older than 30 years. Serum AMH levels were not significantly altered by BMI or smoking., Conclusion(s): The new AMH immunoassay revealed a follicular phase rise in serum levels, particularly in women over the age of 30 years. This is consistent with other reports finding an interaction of menstrual cycle variation in AMH and chronological age. Nonetheless, the extent of variation is small, and sampling on any day of the menstrual cycle is expected to adequately reflect ovarian reserve., Clinical Trial Registration Number: NCT01337999., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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16. The metabolic profile of intrahepatic cholestasis of pregnancy is associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth.
- Author
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Martineau MG, Raker C, Dixon PH, Chambers J, Machirori M, King NM, Hooks ML, Manoharan R, Chen K, Powrie R, and Williamson C
- Subjects
- Adult, Birth Weight physiology, Blood Glucose metabolism, Cholesterol metabolism, Dyslipidemias metabolism, Female, Fetal Macrosomia metabolism, Gestational Age, Glucagon-Like Peptide 1 metabolism, Glucose Intolerance metabolism, Glucose Tolerance Test, Humans, Lipids blood, Male, Metabolic Syndrome metabolism, Metabolome physiology, Pregnancy, Pregnancy Outcome, Prospective Studies, Triglycerides metabolism, Cholestasis, Intrahepatic metabolism, Diabetes, Gestational metabolism, Fetal Development physiology, Pregnancy Complications metabolism
- Abstract
Objective: Quantification of changes in glucose and lipid concentrations in women with intrahepatic cholestasis of pregnancy (ICP) and uncomplicated pregnancy and study of their influence on fetal growth., Research Design and Methods: A prospective study comparing metabolic outcomes in cholestastic and uncomplicated singleton pregnancies was undertaken at two university hospitals in the U.K. and U.S. from 2011-2014. A total of 26 women with ICP and 27 control pregnancies with no prior history of gestational diabetes mellitus were recruited from outpatient antenatal services and followed until delivery. Alterations in glucose, incretins, cholesterol, and triglycerides were studied using a continuous glucose monitoring (CGM) system and/or a standard glucose tolerance test (GTT) in conjunction with GLP-1 and a fasting lipid profile. Fetal growth was quantified using adjusted birth centiles., Results: Maternal blood glucose concentrations were significantly increased in ICP during ambulatory CGM (P < 0.005) and following a GTT (P < 0.005). ICP is characterized by increased fasting triglycerides (P < 0.005) and reduced HDL cholesterol (P < 0.005), similar to changes observed in metabolic syndrome. The offspring of mothers with ICP had significantly larger customized birth weight centiles, adjusted for ethnicity, sex, and gestational age (P < 0.005)., Conclusions: ICP is associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth. These findings may have implications regarding the future health of affected offspring., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
- Published
- 2015
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17. Randomised controlled trial comparing hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors: a pilot study.
- Author
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Maclaughlan David S, Salzillo S, Bowe P, Scuncio S, Malit B, Raker C, Gass JS, Granai CO, and Dizon DS
- Abstract
Objectives: To compare the efficacy of hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors, and to evaluate the feasibility of conducting a clinical trial comparing a drug with a complementary or alternative method (CAM)., Design: Prospective randomised trial., Setting: Breast health centre of a tertiary care centre., Participants: 15 women with a personal history of breast cancer or an increased risk of breast cancer who reported at least one daily hot flash., Interventions: Gabapentin 900 mg daily in three divided doses (control) compared with standardised hypnotherapy. Participation lasted 8 weeks., Outcome Measures: The primary endpoints were the number of daily hot flashes and hot flash severity score (HFSS). The secondary endpoint was the Hot Flash Related Daily Interference Scale (HFRDIS)., Results: 27 women were randomised and 15 (56%) were considered evaluable for the primary endpoint (n=8 gabapentin, n=7 hypnotherapy). The median number of daily hot flashes at enrolment was 4.5 in the gabapentin arm and 5 in the hypnotherapy arm. HFSS scores were 7.5 in the gabapentin arm and 10 in the hypnotherapy arm. After 8 weeks, the median number of daily hot flashes was reduced by 33.3% in the gabapentin arm and by 80% in the hypnotherapy arm. The median HFSS was reduced by 33.3% in the gabapentin arm and by 85% in the hypnotherapy arm. HFRDIS scores improved by 51.6% in the gabapentin group and by 55.2% in the hypnotherapy group. There were no statistically significant differences between groups., Conclusions: Hypnotherapy and gabapentin demonstrate efficacy in improving hot flashes. A definitive trial evaluating traditional interventions against CAM methods is feasible, but not without challenges. Further studies aimed at defining evidence-based recommendations for CAM are necessary., Trial Registration: clinicaltrials.gov (NCT00711529).
- Published
- 2013
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18. Effect of laparoscopic adjustable gastric banding on metabolic syndrome and its risk factors in morbidly obese adolescents.
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Conroy R, Lee EJ, Jean A, Oberfield SE, Sopher A, Kiefer K, Raker C, McMahon DJ, Zitsman JL, and Fennoy I
- Abstract
We examined the effect of laparoscopic adjustable gastric banding (LAGB) on weight loss, inflammatory markers, and components of the Metabolic Syndrome (MeS) in morbidly obese adolescents and determined if those with MeS lose less weight post-LAGB than those without. Data from 14-18 yr adolescents were obtained at baseline, 6 and 12 months following LAGB. Significant weight loss and improvements in MeS components were observed 6 months and one year following LAGB. The incidence of MeS declined 56.8% after 6 months and 69.6% after 12 months. There was no significant difference in amount of weight lost post-LAGB between those with and without MeS at either timepoint. Correlations between change in weight parameters and components of MeS in those with and without MeS at baseline were examined and found to vary by diagnostic category. LAGB is effective for short-term improvement in weight, inflammatory markers, and components of MeS in morbidly obese adolescents.
- Published
- 2011
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19. thy/liv-SCID-hu mice: a system for investigating the in vivo effects of multidrug therapy on plasma viremia and human immunodeficiency virus replication in lymphoid tissues.
- Author
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Pettoello-Mantovani M, Kollmann TR, Katopodis NF, Raker C, Kim A, Yurasov S, Wiltshire H, and Goldstein H
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- Animals, Anti-HIV Agents pharmacokinetics, Chronic Disease, Drug Resistance, Microbial, Drug Therapy, Combination, Fetal Tissue Transplantation, Flow Cytometry, HIV Infections prevention & control, HIV-1 growth & development, Lamivudine therapeutic use, Leukocytes, Mononuclear virology, Liver Transplantation, Mice, Mice, SCID, RNA, Viral analysis, RNA, Viral blood, RNA, Viral drug effects, Recurrence, Ritonavir pharmacokinetics, Saquinavir pharmacokinetics, Thymus Gland embryology, Thymus Gland transplantation, Zidovudine therapeutic use, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, Ritonavir therapeutic use, Saquinavir therapeutic use, Viremia drug therapy
- Abstract
Modified, human immunodeficiency virus (HIV)-inoculated thy/liv-SCID-hu mice were used to evaluate the in vivo efficacy of antiretroviral drugs. Ritonavir treatment alone initially suppressed plasma viremia, but the viremia recurred with the appearance of ritonavir-resistant HIV isolates. Multidrug therapy suppressed plasma HIV RNA to undetectable levels; however, plasma viremia returned after therapy was stopped, showing that the therapy did not completely suppress HIV infection in the thymic implant. When thy/liv-SCID-hu mice were treated with a combination of zidovudine, lamivudine, and ritonavir immediately after inoculation with HIV, cocultures of the thymic implants remained negative for HIV even 1 month after therapy was discontinued, suggesting that acute treatment can prevent the establishment of HIV infection. Thus, these modified thy/liv-SCID-hu mice should prove to be a useful system for evaluating the effectiveness of different antiretroviral therapies on acute and chronic HIV infection.
- Published
- 1998
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20. Mice transgenic for human CD4 and CCR5 are susceptible to HIV infection.
- Author
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Browning J, Horner JW, Pettoello-Mantovani M, Raker C, Yurasov S, DePinho RA, and Goldstein H
- Subjects
- Animals, CD4 Antigens immunology, Genetic Predisposition to Disease, HIV Infections immunology, Humans, Mice, Mice, Transgenic, Receptors, CCR5 immunology, CD4 Antigens genetics, HIV Infections genetics, HIV-1, Receptors, CCR5 genetics
- Abstract
HIV entry into human cells is mediated by CD4 acting in concert with one of several members of the chemokine receptor superfamily. The resistance to HIV infection observed in individuals with defective CCR5 alleles indicated that this particular chemokine receptor plays a crucial role in the initiation of in vivo HIV infection. Expression of human CD4 transgene does not render mice susceptible to HIV infection because of structural differences between human and mouse CCR5. To ascertain whether expression of human CD4 and CCR5 is sufficient to make murine T lymphocytes susceptible to HIV infection, the lck promoter was used to direct the T cell-specific expression of human CD4 and CCR5 in transgenic mice. Peripheral blood mononuclear cells and splenocytes isolated from these mice expressed human CD4 and CCR5 and were infectible with selected M-tropic HIV isolates. After in vivo inoculation, HIV-infected cells were detected by DNA PCR in the spleen and lymph nodes of these transgenic mice, but HIV could not be cultured from these cells. This indicated that although transgenic expression of human CD4 and CCR5 permitted entry of HIV into the mouse cells, significant HIV infection was prevented by other blocks to HIV replication present in mouse cells. In addition to providing in vivo verification for the important role of CCR5 in T lymphocyte HIV infection, these transgenic mice represent a new in vivo model for understanding HIV pathogenesis by delineating species-specific cellular factors required for productive in vivo HIV infection. These mice should also prove useful for the assessment of potential therapeutic and preventative modalities, particularly vaccines.
- Published
- 1997
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21. Severe combined immunodeficiency mice engrafted with human T cells, B cells, and myeloid cells after transplantation with human fetal bone marrow or liver cells and implanted with human fetal thymus: a model for studying human gene therapy.
- Author
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Yurasov S, Kollmann TR, Kim A, Raker CA, Hachamovitch M, Wong-Staal F, and Goldstein H
- Subjects
- Animals, Blood Cell Count, Bone Marrow Transplantation, Cell Differentiation, Graft Survival, Humans, Liver Transplantation, Mice, Mice, SCID, B-Lymphocytes transplantation, Fetal Tissue Transplantation, Genetic Therapy, Hematopoietic Stem Cell Transplantation methods, T-Lymphocytes transplantation, Thymus Gland transplantation
- Abstract
To develop an in vivo model wherein human hematopoiesis occurs, we transplanted severe combined immunodeficiency (SCID) mice with either human fetal bone marrow (HFBM) or human fetal liver (HFL). After transplantation of SCID mice with cultured HFBM (BM-SCID-hu mice) or HFL cells (Liv-SCID-hu mice), significant engraftment of the mouse bone marrow (BM) and population of the peripheral blood with human leukocytes was detected. Human colony-forming unit-granulocyte macrophage and burst forming unit-erythroid were detected in the BM of the BM-SCID-hu and Liv-SCID-hu mice up to 8 months after transplantation. When the HFBM or HFL cells were transduced with a retroviral vector before transplantation, integrated retroviral sequences were detected in human precursor cells present in the SCID mouse BM and in leukocytes circulating in the peripheral blood (PB) up to 7 months after transplantation. The PB of the BM-SCID-hu mice also became populated with human T cells after implantation with human thymic tissue, which provided a human microenvironment wherein human pre-T cells from the BM could mature. When the HFBM was retrovirally transduced before transplantation, integrated retrovirus was detected in sorted CD4+CD8+ double positive and CD4+ single positive cells from the thymic implant and CD4+ cells from the PB. Taken together, these data indicated that the BM of our BM-SCID-hu and Liv-SCID-hu mice became engrafted with retrovirally transduced human hematopoietic precursors that undergo the normal human hematopoietic program and populate the mouse PB with human cells containing integrated retroviral sequences. In addition to being a model for studying in vivo human hematopoiesis, these mice should also prove to be a useful model for investigating in vivo gene therapy using human stem/precursor cells.
- Published
- 1997
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