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1.
J Cyst Fibros ; 23(3): 490-498, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38448281

RESUMEN

BACKGROUND: Cystic fibrosis associated liver disease (CFLD) carries a significant disease burden with no effective preventive therapies. According to the gut-liver axis hypothesis for CFLD pathogenesis, dysbiosis and increased intestinal inflammation and permeability permit pathogenic bacterial translocation into the portal circulation, leading to hepatic inflammation and fibrosis. Evaluating the effect of CFTR (cystic fibrosis transmembrane conductance regulator) modulation with elexacaftor/tezacaftor/ivacaftor (ETI) may help determine the role of CFTR in CFLD and increase understanding of CFLD pathogenesis, which is critical for developing therapies. We aimed to characterize the fecal microbiota in participants with CF with and without advanced CFLD (aCFLD) before and after ETI. METHODS: This is an ancillary analysis of stool samples from participants ages ≥12 y/o enrolled in PROMISE (NCT04038047). Included participants had aCFLD (cirrhosis with or without portal hypertension, or non-cirrhotic portal hypertension) or CF without liver disease (CFnoLD). Fecal microbiota were defined by shotgun metagenomic sequencing at baseline and 1 and 6 months post-ETI. RESULTS: We analyzed 93 samples from 34 participants (11 aCFLD and 23 CFnoLD). Compared to CFnoLD, aCFLD had significantly higher baseline relative abundances of potential pathogens Streptococcus salivarius and Veillonella parvula. Four of 11 aCFLD participants had an initially abnormal fecal calprotectin that normalized 6 months post-ETI, correlating with a significant decrease in S. salivarius and a trend towards decreasing V. parvula. CONCLUSIONS: These results support an association between dysbiosis and intestinal inflammation in CFLD with improvements in both post-ETI, lending further support to the gut-liver axis in aCFLD.


Asunto(s)
Aminofenoles , Benzodioxoles , Fibrosis Quística , Heces , Microbioma Gastrointestinal , Indoles , Quinolonas , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Aminofenoles/uso terapéutico , Benzodioxoles/uso terapéutico , Agonistas de los Canales de Cloruro/uso terapéutico , Fibrosis Quística/microbiología , Fibrosis Quística/tratamiento farmacológico , Combinación de Medicamentos , Disbiosis/microbiología , Disbiosis/etiología , Heces/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Indoles/uso terapéutico , Hepatopatías/microbiología , Hepatopatías/etiología , Pirazoles/uso terapéutico , Piridinas , Pirroles/administración & dosificación , Pirrolidinas , Quinolonas/uso terapéutico
2.
Pediatr Transplant ; 28(1): e14670, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38149456

RESUMEN

BACKGROUND: Deoxyguanosine kinase (DGUOK) deficiency is a rare mitochondrial disorder characterized by early onset liver failure and varying degrees of neurologic dysfunction. Patients typically present during infancy with progressive hepatic dysfunction leading to liver failure, which can precede neurologic deterioration. Outcomes posttransplantation are historically worse than average and the role of liver transplantation remains controversial. These factors, in combination with the increasing number of patients being diagnosed via molecular genetic testing, may impede waitlist access. METHODS: We report our single-center experience with three patients with DGUOK deficiency, all of whom were considered for transplant. We review the current literature regarding management and discuss the role of liver transplantation in DGUOK deficiency-associated liver failure. RESULTS: Two patients presented with hypoglycemia, conjugated hyperbilirubinemia, and lactic acidosis within the first week of life, were diagnosed with DGUOK deficiency prior to 2 months of age and had severe neurologic involvement. The third patient presented in later infancy was diagnosed with DGUOK deficiency at 18 months of age and had minimal neurologic involvement. All three patients were considered for transplant, though only two patients were listed. All three died from complications of end-stage liver failure prior to liver transplantation between the ages of 5-20 months. CONCLUSION: Selection for liver transplantation in DGUOK deficiency is complex, requiring a multidisciplinary team approach. Recent data suggest that liver transplantation can be successful in select patients with absent or mild neurologic manifestations. National databases reporting long-term outcomes posttransplantation are needed.


Asunto(s)
Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Enfermedades Mitocondriales , Humanos , Lactante , ADN Mitocondrial/genética , Enfermedad Hepática en Estado Terminal/cirugía
3.
Neoreviews ; 24(7): e414-e430, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37391660

RESUMEN

See Bonus NeoBriefs videos and downloadable teaching slides Gastrointestinal complications of cystic fibrosis (CF) are often the earliest manifestations of disease and contribute to significant morbidity and mortality. Early diagnosis of CF is paramount, as early intervention has been associated with improved long-term pulmonary and nutritional outcomes. In this review, we describe common gastrointestinal, pancreatic, hepatic, and nutritional manifestations of CF in neonates to aid clinicians in diagnosing and managing the earliest gastrointestinal manifestations of CF. Furthermore, we discuss how the use of CFTR-targeted therapies by pregnant and/or breastfeeding persons may affect CF diagnosis in newborns and their potential impact on halting or reversing CF disease progression.


Asunto(s)
Fibrosis Quística , Enfermedades Gastrointestinales , Recién Nacido , Humanos , Femenino , Embarazo , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico , Fibrosis Quística/terapia , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/terapia
4.
Pediatr Blood Cancer ; 69(11): e29970, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36094280

RESUMEN

Blue rubber bleb nevus syndrome (BRBNS) commonly presents with anemia from bleeding gastrointestinal (GI) vascular malformations. Management is highly variable, as no consensus guidelines for medical treatment currently exist. Sirolimus has been used in BRBNS to decrease GI bleeding and seems well tolerated, though questions remain regarding dosing, duration of therapy, and adverse effects. Here, we report our single-center experience of four pediatric patients with BRBNS who were successfully treated with sirolimus and review the existing literature regarding sirolimus for treatment of GI bleeding in BRBNS. Further prospective studies are needed to establish optimal dosage, drug monitoring, and duration.


Asunto(s)
Neoplasias Gastrointestinales , Nevo Azul , Neoplasias Cutáneas , Niño , Neoplasias Gastrointestinales/complicaciones , Neoplasias Gastrointestinales/tratamiento farmacológico , Humanos , Nevo Azul/complicaciones , Nevo Azul/tratamiento farmacológico , Sirolimus/efectos adversos , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/tratamiento farmacológico , Síndrome
5.
Artículo en Inglés | MEDLINE | ID: mdl-31507536

RESUMEN

Our previous work showed that the G protein-coupled estrogen receptor (GPER) is protective in the vasculature and kidneys during angiotensin (Ang) II-dependent hypertension by inhibiting oxidative stress. The goal of the current study was to assess the impact of GPER deletion on sex differences in Ang II-induced hypertension and oxidative stress. Male and female wildtype and GPER knockout mice were implanted with radiotelemetry probes for measurement of baseline blood pressure before infusion of Ang II (700 ng/kg/min) for 2 weeks. Mean arterial pressure was increased to the same extent in all groups, but female wildtype mice were protected from Ang II-induced increases in pulse pressure, aortic wall thickness, and Nox4 mRNA. In vitro studies using vascular smooth muscle cells found that pre-treatment with the GPER agonist G-1 inhibited Ang II-induced ROS and NADP/NADPH. Ang II increased while G-1 decreased Nox4 mRNA and protein. The effects of Ang II were blocked by losartan and Nox4 siRNA, while the effects of G-1 were inhibited by adenylyl cyclase inhibition and mimicked by phosphodiesterase inhibition. We conclude that during conditions of elevated Ang II, GPER via the cAMP pathway suppresses Nox4 transcription to limit ROS production and prevent arterial stiffening. Taken together with our previous work, this study provides insight into how acute estrogen signaling via GPER provides cardiovascular protection during Ang II hypertension and potentially other diseases characterized by increased oxidative stress.

8.
Perm J ; 22: 17-170, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30227906

RESUMEN

INTRODUCTION: Preeclampsia with severe hypertension, which occurs in 5% to 8% of pregnancies, is a leading cause of maternal and perinatal morbidity and mortality in the US. Early recognition and treatment of hypertensive crises can significantly reduce poor outcomes. A protocol to ensure prompt treatment with antihypertensive medication (intravenous labetalol) was implemented at our institution. OBJECTIVE: To determine adherence to this protocol on the Labor and Delivery Unit. DESIGN: Retrospective chart review was performed for patients admitted to the Labor and Delivery Unit between April 2015 and June 2015. Charts were reviewed if the patient had a diagnosis of chronic hypertension, gestational hypertension, superimposed preeclampsia, preeclampsia with severe features, eclampsia, or stroke in pregnancy. Only patients with confirmed severe blood pressures, in which the protocol would be initiated, were included in the final analysis. MAIN OUTCOME MEASURE: Overall compliance with the entire protocol. RESULTS: Of 178 cases reviewed, 58 (32.6%) had confirmed severe blood pressures. Most patients (n = 46, 79.3%) received a diagnosis of preeclampsia with severe features, and most delivered via cesarean delivery (n = 38, 65.5%). No cases were compliant with the entire labetalol protocol. Of 58 patients, 2 (3.5) adequately repeated a confirmation blood pressure within 5 minutes, and 34 (58.6%) were adequately treated with intravenous labetalol according to protocol requirements. CONCLUSION: Labetalol treatment was appropriately initiated in many cases; however, protocol adherence could greatly improve. Potential factors affecting protocol compliance include shift changes, communication issues, and conflicting protocols. Institutions should review protocol compliance to improve care.


Asunto(s)
Antihipertensivos/uso terapéutico , Parto Obstétrico/métodos , Adhesión a Directriz/estadística & datos numéricos , Hipertensión/tratamiento farmacológico , Labetalol/uso terapéutico , Preeclampsia/tratamiento farmacológico , Algoritmos , Salas de Parto , Femenino , Humanos , Recién Nacido , Trabajo de Parto , Embarazo , Estudios Retrospectivos
9.
Perm J ; 22: 17-204, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30010531

RESUMEN

CONTEXT: Results from chromosome testing after spontaneous abortion (SAB) or intrauterine fetal demise (IUFD) are useful in patient counseling; however, results can be inconclusive when cell cultures for chromosomes are unable to grow from products of conception. Chromosomal microarray analysis (CMA) can analyze DNA from nonviable fetal tissue. OBJECTIVE: To examine whether establishing a genetic testing protocol for karyotype and CMA on SAB and IUFD tissues increases diagnostic yield. DESIGN: A retrospective chart review was conducted in cases of SAB or IUFD when karyotyping and/or CMA was requested, comparing two periods: Preprotocol and postprotocol implementation. MAIN OUTCOME MEASURES: Diagnostic yield was compared by using the number of determinate test results in the preprotocol and postprotocol study periods. A case was considered to have indeterminate results when the final genetic test results reported no fetal tissue or no cell culture growth. RESULTS: A total of 55 preprotocol and 52 postprotocol patients were analyzed. Diagnostic yield increased from 72.7% to 94.2% after implementation of the genetic testing protocol (p = 0.0004). Indeterminate results occurred more frequently before compared with after implementation of the protocol. CONCLUSION: A protocol of reflexing to CMA or proceeding directly with CMA gives a higher diagnostic yield in the genetic evaluation of SAB or IUFD. Institutions should consider implementing a genetic testing protocol to improve diagnostic yield. Our study results emphasize the importance of proceeding directly to microarray analysis and give support for current clinical recommendations for genetic testing after fetal demise.


Asunto(s)
Aborto Espontáneo/diagnóstico , Aberraciones Cromosómicas , Trastornos de los Cromosomas/diagnóstico , Pruebas Genéticas/métodos , Análisis por Micromatrices/métodos , Mortinato , Femenino , Humanos , Cariotipificación , Embarazo , Estudios Retrospectivos
10.
Am J Obstet Gynecol ; 219(5): 488.e1-488.e7, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29902447

RESUMEN

BACKGROUND: Intravesical injection with onabotulinum toxin A injection can be performed in-office under local anesthesia. Rectally administered pain medication presents a potentially feasible and previously uninvestigated adjunct to office-based anesthesia protocols. OBJECTIVE: The primary aim of this study was to determine whether adding a belladonna and opiate suppository to standard lidocaine instillation resulted in reduction of bladder injection pain during onabotulinum toxin A injection procedure. STUDY DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study of patients undergoing onabotulinum toxin A bladder injection at a single clinic. Patients age ≥18 years, who met clinical criteria for invasive treatment of refractory urinary symptoms, had previously documented postvoid residual volumes <150 mL, and elected for in-office intravesical onabotulinum toxin A injection were eligible to participate. Participants were randomized by computer-generated block randomization to receive a belladonna and opiate (belladonna alkaloid with morphine 16.2/7.5 mg) or placebo suppository. Suppositories were placed immediately prior to lidocaine-based anesthesia, which all participants received. All participants underwent a standardized injection procedure using the same rigid cystoscope, needle type, and injection pattern (20 injections total). A 0-10 numeric rating scale was used to assess pain intensity before anesthesia and suppository, 40 minutes after administration of anesthesia and suppository, after first 10 bladder injections, and immediately after completion of 20 injections. Pain increase during procedure was calculated using the difference between score 40 minutes after administration of anesthesia and suppository and score after first 10 bladder injections. Postvoid residual were measured immediately postprocedure and 2 weeks later. Patient satisfaction with pain control was measured using a Likert scale. Our primary outcome was change in pain level from anesthetic baseline to midprocedure (score after first 10 bladder injections to score 40 minutes after administration of anesthesia and suppository). A final sample size of 26 patients was needed to have 80% power (alpha = 0.05) to detect a 50% reduction in bladder injection pain during the procedure as defined by our primary outcome. An intent-to-treat approach was used for all analyses. RESULTS: In all, 26 participants were enrolled and randomized with 13 in each study arm. Participants in the treatment group were slightly older than in the placebo group (P = .05); there were no statistically significant differences in medical comorbidities. Median score after first 10 bladder injections to score 40 minutes after administration of anesthesia and suppository for the placebo group and treatment group was 4 (range 1-10) and 5 (range 0,9), respectively (P = .94). Median scores immediately after completion of 20 injections for the placebo group and treatment group were 3 (range 0-10) and 2 (range 0,8), respectively (P = .29). There were no significant differences in preinjection pain scores reported before anesthesia and suppository and at 40 minutes after administration of anesthesia and suppository. Postprocedure postvoid residual >200 mL was noted in 5 (38%) of the placebo group and 3 (23%) of the treatment group (P = .67). Two-week postprocedure postvoid residual >200 mL was noted in 3 (25%) of the placebo group and 2 (15%) of the treatment group (P = .64) for an overall rate of 20%. Eleven (84%) participants in each group reported being "mostly satisfied" or "very much satisfied" with pain control. CONCLUSION: Belladonna and opiate suppository use did not significantly reduce bladder injection pain, or increase risk of urinary retention immediately postprocedure or 2 weeks later. Satisfaction with pain control among onabotulinum toxin A injection patients is high.


Asunto(s)
Analgésicos , Alcaloides de Belladona/administración & dosificación , Toxinas Botulínicas Tipo A/administración & dosificación , Morfina/administración & dosificación , Vejiga Urinaria/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Anestesia , Alcaloides de Belladona/efectos adversos , Método Doble Ciego , Femenino , Humanos , Inyecciones , Lidocaína/administración & dosificación , Persona de Mediana Edad , Morfina/efectos adversos , Dimensión del Dolor , Satisfacción del Paciente , Placebos , Estudios Prospectivos , Supositorios , Resultado del Tratamiento , Retención Urinaria/inducido químicamente , Retención Urinaria/epidemiología
11.
J Behav Med ; 41(5): 653-667, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29721813

RESUMEN

In the United States, more than 9 million rural women (15-44 years old) experience limited access and delivery of reproductive healthcare services. Rurality coupled with lower socio-economic status are associated with increased maternal and neonatal morbidity and mortality. The purpose of this qualitative study was to gain in-depth information from underserved English- and Spanish-speaking pregnant and postpartum rural women on what they would value in a health promotion program. Three focus group sessions were conducted exploring four domains: (1) physical activity, (2) dietary habits, (3) fetal movement/kick counts, and (4) breastfeeding and other support resources. Five overarching themes were observed across domains, with the following health promotion needs: (1) information on safe exercises, (2) advice on healthy food and drink, (3) breastfeeding support, (4) guidance on counting fetal movement, and (5) self- and peer-education. Study findings will inform intervention programming that aims to improve pregnancy and birth outcomes.


Asunto(s)
Promoción de la Salud/organización & administración , Servicios de Salud Materna/organización & administración , Periodo Posparto , Servicios de Salud Rural/organización & administración , Población Rural/estadística & datos numéricos , Adolescente , Adulto , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Lactante , Atención Posnatal/organización & administración , Embarazo , Adulto Joven
12.
Kans J Med ; 11(2): 1-19, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29796155

RESUMEN

BACKGROUND: A potential non-pharmacologic way to reduce postoperative pain and bleeding is using an abdominal binder during postoperative recovery. This study aims to determine the effect an elastic abdominal binder has on postoperative pain and hemorrhage after cesarean delivery. METHODS: A randomized, single-site, pilot trial was conducted at two prenatal care clinics and an academic hospital in Kansas. Beginning in April 2013, 60 patients were enrolled if delivering via cesarean. Participants were randomized to receive an abdominal binder or to a control group (did not use binder). Pain levels were reported by questionnaire one day after surgery using a 0 to 10 scale, with 10 being the worst pain. Patient characteristics and blood loss were assessed by medical record review. RESULTS: Of the 56 patients completing the study, 29 (51.8%) were randomized to the binder group and 27 (48.2%) were randomized to the control group. The binder group reported significantly lower pain score (p = 0.019) and average pain score (p = 0.024). There was no difference in body mass index, age, previous surgery, infant birth weight, estimated blood loss, and average dose of pain medication during the first 24 hours after the cesarean delivery between the two groups. There was no difference in pre- and post-operative hemoglobin levels by treatment group (p = 0.406). CONCLUSIONS: Abdominal binders may be associated with improved postoperative pain scores but did not affect postoperative hemorrhage.

13.
Methods Mol Biol ; 1760: 163-186, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29572803

RESUMEN

Nestin-expressing hair follicle-associated pluripotent (HAP) stem cells reside mainly in the bulge area (BA) of the hair follicle but also in the dermal papilla (DP). The BA appears to be origin of HAP stem cells. Long-term Gelfoam® histoculture was established of whiskers isolated from transgenic mice, in which there is nestin-driven green fluorescent protein (ND-GFP). HAP stem cells trafficked from the BA toward the DP area and extensively grew out onto Gelfoam® forming nerve-like structures. These fibers express the neuron marker ß-III tubulin-positive fibers and consisted of ND-GFP-expressing cells and extended up to 500 mm from the whisker nerve stump in Gelfoam® histoculture. The growing fibers had growth cones on their tips expressing F-actin indicating that the fibers were growing axons. HAP stem cell proliferation resulted in elongation of the follicle nerve and interaction with other nerves in 3D Gelfoam® histoculture, including the sciatic nerve, trigeminal nerve, and trigeminal nerve ganglion.


Asunto(s)
Técnicas de Cultivo de Célula , Tejido Nervioso/citología , Tejido Nervioso/crecimiento & desarrollo , Técnicas de Cultivo de Tejidos , Animales , Movimiento Celular , Expresión Génica , Genes Reporteros , Folículo Piloso/citología , Ratones , Ratones Transgénicos , Microscopía Fluorescente , Nestina/genética , Nestina/metabolismo , Neurogénesis , Imagen Óptica , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , Nervio Ciático/citología , Nervio Ciático/crecimiento & desarrollo , Nervio Trigémino/citología , Nervio Trigémino/crecimiento & desarrollo , Vibrisas
14.
J Womens Health (Larchmt) ; 27(7): 859-866, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29583064

RESUMEN

BACKGROUND: It is estimated that 1-2.5 million U.S. women use compounded bioidentical menopausal hormone therapy (MHT). However, the proportion of American physicians prescribing compounded bioidentical hormones remains unknown. This study aims to evaluate obstetrician-gynecologists' (OB/GYNs) and family medicine physicians' decisions reflected in prescribing practices of MHT in Kansas, and level of agreement with the American College of Obstetricians and Gynecologists (ACOG) recommendations. METHODS: An Internet-based 38-item survey was electronically disseminated to OB/GYNs and family medicine physicians identified through the Kansas State Board of Healing Arts licensure list. RESULTS: Out of 1349 physicians contacted, 164 (12.2%) responded to the survey. There were 128 (9.5%) responses included in the final analysis. In the past year, 96.1% (123/128) of respondents prescribed conventional MHT, 93.0% (119/128) prescribed Food and Drug Administration (FDA)-approved bioidentical MHT, and 66.1% (84/127) prescribed compounded bioidentical MHT. Of factors influencing MHT-prescribing practices, FDA regulation was not important to 16.7% (21/126) of physicians, whereas customization was important to 68.5% (87/127). There was a significant difference between specialties, 37.7% of OB/GYNs compared with 56.9% of family medicine physicians, regarding the ACOG statement that "patients should be counseled that conventional MHT is more appropriate than compounded preparations" (p = 0.031). Respondents disagreed with ACOG regarding the statements that "the practice of compounding makes it difficult to identify the active agent responsible for various effects" (41.0% of OB/GYNs and 34.8% of family medicine physicians) and "the practice of custom blending commercially available drug products lacks both a strong biological rationale and medical evidence for effectiveness" (36.1% of OB/GYNs and 37.9% of family medicine physicians). CONCLUSIONS: Prescribing practices for MHT vary between specialties. This study identifies a meaningful level of disagreement with ACOG recommendations regarding prescription of compounded rather than FDA-approved MHT. Further research is needed to better understand this level of discordance.


Asunto(s)
Composición de Medicamentos , Terapia de Reemplazo de Estrógeno , Menopausia/efectos de los fármacos , Pautas de la Práctica en Medicina , Actitud del Personal de Salud , Femenino , Ginecología/estadística & datos numéricos , Humanos , Persona de Mediana Edad , Obstetricia/estadística & datos numéricos , Médicos , Médicos de Familia , Encuestas y Cuestionarios , Estados Unidos
15.
Surg Infect (Larchmt) ; 19(4): 397-402, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29451847

RESUMEN

BACKGROUND: The purpose of this study was to establish compliance with guidelines published by the American College of Obstetricians and Gynecologists (ACOG) regarding prophylactic antibiotic use in gynecologic surgery at our institution, and define areas of improvement to promote antibiotic stewardship. PATIENTS AND METHODS: This was a retrospective cohort study at a single, large tertiary care and teaching hospital in Kansas. Patients who underwent inpatient or outpatient gynecologic surgery during 2013 were included. Based on published guidelines for prophylactic antibiotic agents for gynecologic surgery by ACOG, procedures were classified as antibiotic-indicated or antibiotic-not-indicated. Chi-square and Fisher exact test analysis were used to identify factors associated with antibiotic use. RESULTS: Of the 1,735 cases eligible for inclusion, 1,045 (60.2%) had antibiotic agents recommended per guidelines, and appropriate antibiotic agents were given in 1,031 (98.7%) of those cases. In 690 (39.8%) cases, prophylactic antibiotics were either not recommended or the guidelines are not well defined. Of the 690 cases without indication for antibiotic agents, 394 (57.1%) received prophylactic antibiotic agents. Agreement with guidelines varied substantially based on patient age, race, insurance status, area of residence, and if the procedure was a resident case (p < 0.05). Myomectomy, laparoscopy, and ectopic pregnancy procedures received antibiotic agents against recommendations 96.3%, 75.6%, and 45.5% of the time, respectively. CONCLUSIONS: Peri-operative antibiotics are often administered inappropriately to women undergoing gynecologic surgeries for which published guidelines are not well defined. Future studies need to identify strategies to reduce antibiotic use in surgical procedures unlikely to benefit from prophylaxis.


Asunto(s)
Antibacterianos/administración & dosificación , Profilaxis Antibiótica/métodos , Adhesión a Directriz , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Infección de la Herida Quirúrgica/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Investigación sobre Servicios de Salud , Hospitales de Enseñanza , Humanos , Kansas , Persona de Mediana Edad , Estudios Retrospectivos , Centros de Atención Terciaria , Adulto Joven
16.
Am J Physiol Renal Physiol ; 312(2): F305-F311, 2017 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-28153915

RESUMEN

Clinical recommendations limit menopausal hormone therapy to a few years, yet the impact of a shorter treatment duration on cardiovascular health is unknown. We hypothesized that both short- and long-term estradiol (E2) treatment exerts positive and lasting effects on blood pressure, vascular reactivity, and renal health. This study was designed to mimic midlife menopause, followed by E2 treatment, that either followed or exceeded the current clinical recommendations. Female Long-Evans retired breeders were ovariectomized (OVX) at 11 mo of age and randomized into three groups: 80-day (80d) vehicle (Veh>Veh), 40-day (40d) E2 + 40d vehicle (E2>Veh), and 80d E2 (E2>E2). In comparison to Veh>Veh, both the E2>Veh and E2>E2 groups had lower systolic blood pressure and enhanced mesenteric relaxation in response to estrogen receptor-α stimulation. Despite the reduced blood pressure, E2>E2 induced renal and cardiac hypertrophy, reduced glomerular filtration, and increased proteinuria. Interestingly, kidneys from E2>Veh rats had significantly fewer tubular casts than both of the other groups. In conclusion, long-term E2 lowered blood pressure but exerted detrimental effects on kidney health in midlife OVX Long-Evans rats, whereas short-term E2 lowered blood pressure and reduced renal damage. These findings highlight that the duration of hormone therapy may be an important factor for renal health in aging postmenopausal women.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Estradiol/administración & dosificación , Riñón/efectos de los fármacos , Animales , Femenino , Arterias Mesentéricas/efectos de los fármacos , Ovariectomía , Ratas , Ratas Long-Evans , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacos
17.
PLoS Pathog ; 12(11): e1005983, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27855210

RESUMEN

HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4. C34-conjugated coreceptors were expressed on the surface of T cell lines and primary CD4 T cells, retained the ability to mediate chemotaxis in response to cognate chemokines, and were highly resistant to HIV-1 utilization for entry. Notably, C34-conjugated CCR5 and CXCR4 each exhibited potent and broad inhibition of HIV-1 isolates from diverse clades irrespective of tropism (i.e., each could inhibit R5, X4 and dual-tropic isolates). This inhibition was highly specific and dependent on positioning of the peptide, as HIV-1 infection was poorly inhibited when C34 was conjugated to the amino terminus of CD4. C34-conjugated coreceptors could also inhibit HIV-1 isolates that were resistant to the soluble HR2 peptide inhibitor, enfuvirtide. When introduced into primary cells, CD4 T cells expressing C34-conjugated coreceptors exhibited physiologic responses to T cell activation while inhibiting diverse HIV-1 isolates, and cells containing C34-conjugated CXCR4 expanded during HIV-1 infection in vitro and in a humanized mouse model. Notably, the C34-conjugated peptide exerted greater HIV-1 inhibition when conjugated to CXCR4 than to CCR5. Thus, antiviral effects of HR2 peptides can be specifically directed to the site of viral entry where they provide potent and broad inhibition of HIV-1. This approach to engineer HIV-1 resistance in functional CD4 T cells may provide a novel cell-based therapeutic for controlling HIV infection in humans.


Asunto(s)
Linfocitos T CD4-Positivos/virología , Proteína gp41 de Envoltorio del VIH/metabolismo , Infecciones por VIH/metabolismo , VIH-1/metabolismo , Fragmentos de Péptidos/metabolismo , Receptores CXCR4/metabolismo , Internalización del Virus , Animales , Linfocitos T CD4-Positivos/metabolismo , Citometría de Flujo , Células HEK293 , Humanos , Ratones , Ratones Endogámicos NOD
18.
Methods Mol Biol ; 1453: 39-47, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27431245

RESUMEN

Mouse whiskers containing hair-follicle-associated pluripotent (HAP) stem cells, from nestin-driven green fluorescent protein (ND-GFP) transgenic mice, were placed in 3D histoculture supported by Gelfoam(®). ß-III tubulin-positive fibers, consisting of ND-GFP-expressing HAP stem cells, extended up to 500 mm from the whisker nerve stump in histoculture. The growing fibers had growth cones on their tips expressing F-actin indicating they were growing axons. The growing whisker sensory nerve was highly enriched in ND-GFP HAP stem cells which appeared to play a major role in its elongation and interaction with other nerves placed in 3D culture, including the sciatic nerve, the trigeminal nerve, and the trigeminal nerve ganglion. The results suggested that a major function of HAP stem cells in the hair follicle is for growth of the hair follicle sensory nerve.


Asunto(s)
Folículo Piloso/citología , Nestina/genética , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , Vibrisas/metabolismo , Animales , Técnicas de Cultivo de Célula , Ganglios/citología , Expresión Génica , Ratones , Ratones Transgénicos , Microscopía Confocal , Nestina/metabolismo , Traumatismos de los Nervios Periféricos , Nervio Ciático/citología
19.
J Grad Med Educ ; 7(3): 412-6, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26457148

RESUMEN

BACKGROUND: Resident physicians provide much of the clinical teaching for medical students during their clerkship rotations, but often receive no formal preparation or structure for teaching and mentoring students. OBJECTIVE: We sought to evaluate a medical student mentoring program (MSMP) for students during their obstetrics and gynecology clerkship at a midwestern teaching hospital during the 2013-2014 academic year. METHODS: A senior resident physician was assigned 1 to 2 medical students for a 6-week rotation. Students were provided MSMP information during clerkship orientation; residents were given information on MSMP requirements and were randomly assigned to students. We surveyed students and residents about their experience with the MSMP. RESULTS: Of 49 eligible medical students, 43 (88%) completed postsurveys. All students reported not having a mentoring program on other clerkships. Postclerkship, students indicated that they would participate in the MSMP again (32 of 38, 84%), and felt that having a mentor on other clerkships (30 of 36, 83%) would be beneficial. Students reported receiving educational (20 of 41, 49%) and procedural (33 of 41, 80%) instruction, personal development feedback (23 of 41, 56%), and career advice (14 of 41, 34%) from resident mentors. Out of a total of 45 possible surveys by residents, 17 (38%) were completed. Residents did not feel burdened by students (14 of 17, 82%), and all responded that they would participate in the MSMP again. CONCLUSIONS: Feedback from medical students suggests that a mentoring program during clerkships may provide potential benefits for their careers and in 1-on-1 instruction.


Asunto(s)
Prácticas Clínicas , Ginecología/educación , Internado y Residencia , Mentores/educación , Obstetricia/educación , Centros Médicos Académicos , Actitud del Personal de Salud , Humanos , Estudiantes de Medicina
20.
Spine (Phila Pa 1976) ; 39(15): E894-901, 2014 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-24825156

RESUMEN

STUDY DESIGN: Retrospective chart review. OBJECTIVE: To report outcomes of a consecutive series of patients diagnosed with degenerative disc disease (DDD) between L4 and S1, treated with stand-alone anterior lumbar interbody fusion (ALIF, either 1 or 2 levels) and use of recombinant human bone morphogenetic protein 2 for bony fusion with instrumented fixation. SUMMARY OF BACKGROUND DATA: Degeneration of the lumbar spine is described as lumbar spondylosis, or DDD. To treat DDD, surgical interventions include: ALIF, circumferential fusion (360° fusion), posterior spinal fusion, and total disc replacement. Currently, there has been paucity in the literature on the evaluation of ALIFs. METHODS: Researchers reviewed a consecutive series of patients with DDD who had undergone a 1-level or 2-level ALIF between 2005 and 2010, with the use of recombinant human bone morphogenetic protein 2. Patients' clinical and functional outcomes were documented. Radiographs were analyzed for disc height, mean optical density, and integrated optical density. Operative time, length of hospital stay, and estimated blood loss were also reported. RESULTS: Patients' 2-year Oswestry Disability Index and visual analogue scale presurgery scores significantly improved (P ≤ 0.0001). Patients' 2-year postoperative disc height was significantly greater than the preoperative disc height at the fused level (P ≤ 0.0001); there was no significant difference at the level adjacent to fusion. Majority of patients (107 of 115, 93.0%) satisfied fusion criteria based on mean optical density. Intraoperative time, estimated blood loss, and hospital stay was significantly fewer with 1-level and 2-level ALIFs than 360° fusions and total disc replacement. CONCLUSION: Stand-alone ALIF used to treat DDD can produce comparative clinical and functional outcomes. ALIFs showed significant decreases in blood loss, operative time, and hospital stay. Furthermore, at 2 years' time, mean optical density suggests high rate of bony fusion, and no significant loss of disc height was noted at the adjacent level. LEVEL OF EVIDENCE: 4.


Asunto(s)
Degeneración del Disco Intervertebral/cirugía , Vértebras Lumbares/cirugía , Sacro/cirugía , Fusión Vertebral/métodos , Adulto , Pérdida de Sangre Quirúrgica , Proteína Morfogenética Ósea 2/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Región Lumbosacra/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Reeemplazo Total de Disco/métodos , Factor de Crecimiento Transformador beta/uso terapéutico , Resultado del Tratamiento
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