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INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) survivors live with long-term residual physical and cognitive disability. We studied whether neuromuscular electrical stimulation (NMES) and high-protein supplementation (HPRO) in the first 2 weeks after SAH could preserve neuromotor and cognitive function as compared to standard of care (SOC) for nutrition and mobilization. METHODS: SAH subjects with a Hunt Hess (HH) grade > 1,modified Fisher score > 1 and BMI < 40 kg/m2 were randomly assigned to SOC or NMES + HPRO. NMES was delivered to bilateral quadricep muscles daily during two 30-min sessions along with HPRO (goal:1.8 g/kg/day) between post-bleed day (PBD) 0 and 14. Primary endpoint was atrophy in the quadricep muscle as measured by the percentage difference in the cross-sectional area from baseline to PBD14 on CT scan. All subjects underwent serial assessments of physical (short performance physical battery, SPPB) cognitive (Montreal Cognitive Assessment Scale, MoCA) and global functional recovery (modified Rankin Scale, mRS) at PBD 14, 42, and 90. RESULTS: Twenty-five patients (SOC = 13, NMES + HPRO = 12) enrolled between December 2017 and January 2019 with no between-group differences in baseline characteristics (58 years old, 68% women, 50% HH > 3). Median duration of interventions was 12 days (range 9-14) with completion of 98% of NMES sessions and 83% of goal HPRO, and no reported serious adverse events. There was no difference in caloric intake between groups, but HPRO + NMES group received more protein (1.5 ± 0.5 g/kg/d v 0.9 ± 0.4 g/kg/d, P < 0.01). Muscle atrophy was less in NMES + HPRO than the SOC group (6.5 ± 4.1% vs 12.5 ± 6.4%, P 0.01). Higher atrophy was correlated with lower daily protein intake (ρ = - 0.45, P = 0.03) and lower nitrogen balance (ρ = 0.47, P = 0.02); and worse 3 month SPPB (ρ = - 0.31, P = 0.1) and mRS (ρ = 0.4, P = 0.04). NMES + HPRO patients had a better median [25%,75] SPPB (12[10, 12] v. 9 [4, 12], P = 0.01) and mRS (1[0,2] v.2[1, 3], P = 0.04) than SOC at PBD 90. CONCLUSIONS: NMES + HPRO appears to be feasible and safe acutely after SAH and may reduce acute quadriceps muscle wasting with a lasting benefit on recovery after SAH.
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Terapia por Estimulación Eléctrica , Hemorragia Subaracnoidea , Suplementos Dietéticos , Estimulación Eléctrica , Femenino , Humanos , Masculino , Recuperación de la Función , Hemorragia Subaracnoidea/terapiaRESUMEN
PURPOSE: To determine the utility of the endometrial receptivity analysis (ERA) in women with prior failed embryo transfers (ET). METHODS: This was a retrospective study of patients who underwent an ERA test with a subsequent frozen ET. Women were classified based on their indication for an ERA test: (1) ≥ 1 prior failed ET (cases), or (2) as a prophylactic measure (controls). A subset analysis of women with ≥ 3 prior failed transfers was performed. Pregnancy outcomes of the subsequent cycle were examined, including conception, clinical pregnancy, and ongoing pregnancy/live birth. RESULTS: A total of 222 women were included, 131 (59%) women with ≥ 1 prior failed ET and 91 (41%) controls. Among the 131 women with ≥ 1 prior failed ET, 20 women (9%) had ≥ 3 prior failed ETs. The proportion of non-receptive ERA tests in the three groups were the following: 45% (≥ 1 prior failed ET), 40% (≥ 3 prior failed ETs), and 52% (controls). The results did not differ between cases and controls. The pregnancy outcomes did not differ between women with ≥ 1 prior failed ET and controls. In women with ≥ 3 prior failed ETs, there was a lower ongoing pregnancy/live birth rate (28% vs 54%, P = 0.046). CONCLUSION: Women with ≥ 1 prior failed ET and ≥ 3 prior failed ETs had a similar prevalence of non-receptive endometrium compared to controls. Women with ≥ 3 prior failed ETs had a lower ongoing pregnancy/live birth rate despite a personalized FET, suggesting that there are additional factors in implantation failure beyond an adjustment in progesterone exposure.
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Endometrio/fisiopatología , Fertilización In Vitro/métodos , Infertilidad Femenina/terapia , Nacimiento Vivo/epidemiología , Adulto , Implantación del Embrión , Transferencia de Embrión , Femenino , Humanos , Infertilidad Femenina/fisiopatología , Embarazo , Resultado del Embarazo , Índice de Embarazo , Estudios RetrospectivosRESUMEN
The Ewing sarcoma family of tumors (EFT) is a group of highly malignant small round blue cell tumors occurring in children and young adults. We report here the largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines). Using a combination of whole genome sequencing and targeted sequencing approaches, we discover that EFT has a very low mutational burden (0.15 mutations/Mb) but frequent deleterious mutations in the cohesin complex subunit STAG2 (21.5% tumors, 44.4% cell lines), homozygous deletion of CDKN2A (13.8% and 50%) and mutations of TP53 (6.2% and 71.9%). We additionally note an increased prevalence of the BRCA2 K3326X polymorphism in EFT patient samples (7.3%) compared to population data (OR 7.1, pâ=â0.006). Using whole transcriptome sequencing, we find that 11% of tumors pathologically diagnosed as EFT lack a typical EWSR1 fusion oncogene and that these tumors do not have a characteristic Ewing sarcoma gene expression signature. We identify samples harboring novel fusion genes including FUS-NCATc2 and CIC-FOXO4 that may represent distinct small round blue cell tumor variants. In an independent EFT tissue microarray cohort, we show that STAG2 loss as detected by immunohistochemistry may be associated with more advanced disease (pâ=â0.15) and a modest decrease in overall survival (pâ=â0.10). These results significantly advance our understanding of the genomic and molecular underpinnings of Ewing sarcoma and provide a foundation towards further efforts to improve diagnosis, prognosis, and precision therapeutics testing.
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Antígenos Nucleares/genética , Mutación/genética , Proteínas de Neoplasias/genética , Sarcoma de Ewing/genética , Adolescente , Adulto , Proteínas de Ciclo Celular , Línea Celular Tumoral , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Eliminación de Gen , Genoma Humano , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Masculino , Sarcoma de Ewing/etiología , Sarcoma de Ewing/patologíaRESUMEN
Acute scrotal pain is a very common presentation to the emergency room. The most important pathology we must exclude is testicular infarction or testicular ischemia. Here we describe two rare cases of acute scrotum where incarcerated inguinal hernias containing omentum resulted in testicular ischemia/infarction. In Case 1, we describe a rare case in an adult where a large, incarcerated hernia containing omentum along with direct trauma to the testicle resulted in testicular infarction. In Case 2, we describe a 2-year-old boy who presented with left scrotal tenderness due to a left inguinal hernia containing omentum resulting in compromised testicular blood flow. Both patients underwent scrotal exploration. This article also explores the possible pathophysiology of how omentum containing hernias may result in an increased risk of testicular ischemia.
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We present a 67-year-old gentleman with a high perioperative mortality and morbidity risk who presented with spontaneous idiopathic tension pneumoperitoneum that was successfully managed with bedside pig-tail catheter insertion. Here we also discuss other potential non-surgical aetiologies of pneumoperitoneum.
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Parkinson disease affects more than 1% of the population over 60 y old. The dominant models for Parkinson disease are based on the use of chemical toxins to kill dopamine neurons, but do not address the risk factors that normally increase with age. Forkhead transcription factors are critical regulators of survival and longevity. The forkhead transcription factor, foxa2, is specifically expressed in adult dopamine neurons and their precursors in the medial floor plate. Gain- and loss-of-function experiments show this gene, foxa2, is required to generate dopamine neurons during fetal development and from embryonic stem cells. Mice carrying only one copy of the foxa2 gene show abnormalities in motor behavior in old age and an associated progressive loss of dopamine neurons. Manipulating forkhead function may regulate both the birth of dopamine neurons and their spontaneous death, two major goals of regenerative medicine.
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Envejecimiento/fisiología , Dopamina/metabolismo , Regulación del Desarrollo de la Expresión Génica/genética , Factor Nuclear 3-beta del Hepatocito/metabolismo , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/patología , Parto/metabolismo , Animales , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Factor Nuclear 3-beta del Hepatocito/deficiencia , Factor Nuclear 3-beta del Hepatocito/genética , Ratones , Ratones Noqueados , Degeneración Nerviosa/genética , Parto/genéticaRESUMEN
Juvenile polyposis syndrome (JPS) and hereditary haemorrhagic telangiectasia (HHT) are rare autosomal dominant diseases, where symptoms manifest at childhood. A 32-year-old man with no family history of JPS or HHT with SMAD4 gene mutation who developed signs and symptoms only at the age of 32, when he was an adult. In this article, we highlight the steps taken to diagnose this rare pathology, explain its pathophysiology and management.
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Anemia Ferropénica/diagnóstico , Gastritis/diagnóstico , Poliposis Intestinal/congénito , Pólipos Intestinales/diagnóstico , Síndromes Neoplásicos Hereditarios/diagnóstico , Telangiectasia Hemorrágica Hereditaria/diagnóstico , Adulto , Edad de Inicio , Anemia Ferropénica/sangre , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/genética , Colon/diagnóstico por imagen , Colon/patología , Endoscopía Gastrointestinal , Gastrectomía , Mucosa Gástrica/diagnóstico por imagen , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/microbiología , Gastritis/patología , Gastritis/cirugía , Helicobacter heilmannii/aislamiento & purificación , Hematínicos/administración & dosificación , Humanos , Hiperplasia , Mucosa Intestinal/diagnóstico por imagen , Mucosa Intestinal/patología , Poliposis Intestinal/complicaciones , Poliposis Intestinal/diagnóstico , Poliposis Intestinal/genética , Pólipos Intestinales/genética , Masculino , Mutación , Síndromes Neoplásicos Hereditarios/complicaciones , Síndromes Neoplásicos Hereditarios/genética , Índice de Severidad de la Enfermedad , Proteína Smad4/genética , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/genética , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: Walker-Warburg syndrome (WWS) is a genetically heterogeneous congenital muscular dystrophy caused by abnormal glycosylation of alpha-dystroglycan (alpha-DG) that is associated with brain malformations and eye anomalies. The Fukutin (FKTN) gene, which causes autosomal recessively inherited WWS is most often associated with Fukuyama congenital muscular dystrophy in Japan. We describe the clinical features of four nonconsanguinous Ashkenazi Jewish families with WWS and identify the underlying genetic basis for WWS. METHOD: We screened for mutations in POMGnT1, POMT1, POMT2, and FKTN, genes causing WWS, by dideoxy sequence analysis. RESULTS: We identified an identical homozygous c.1167insA mutation in the FKTN gene on a common haplotype in all four families and identified 2/299 (0.7%) carriers for the c.1167insA mutation among normal American Ashkenazi Jewish adults. CONCLUSION: These data suggest that the c.1167insA FKTN mutation described by us is a founder mutation that can be used to target diagnostic testing and carrier screening in the Ashkenazi Jewish population.
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Encéfalo/anomalías , Judíos/genética , Proteínas de la Membrana/genética , Distrofias Musculares/genética , Mutación , Ultrasonografía Prenatal , Adulto , Preescolar , Exones , Resultado Fatal , Femenino , Haplotipos , Humanos , Lactante , Recién Nacido , Masculino , Distrofias Musculares/diagnóstico por imagen , Linaje , Embarazo , SíndromeRESUMEN
Macaca fascicularis, also known as the cynomolgus macaque, is an important non-human primate animal model used in biomedical research. It is an Old-World primate widely distributed in Southeast Asia and is one of the most abundant macaque species in Malaysia. However, the genetic structure of wild cynomolgus macaque populations in Malaysia has not been thoroughly elucidated. In this study, we developed genic-simple sequence repeat (genic-SSR) markers from an in-house transcriptome dataset generated from the Malaysian cynomolgus macaque via RNA sequencing, and applied these markers on 26 cynomolgus macaque individuals. A collection of 14,751 genic-SSRs were identified, where 13,709 were perfect SSRs. Dinucleotide repeats were the most common repeat motifs with a frequency of 65.05%, followed by trinucleotide repeats (20.55%). Subsequently, we designed 300 pairs of primers based on perfect di- and trinucleotide SSRs, in which 105 SSRs were associated with functional genes. A subset of 30 SSR markers were randomly selected and validated, yielding 19 polymorphic markers with an average polymorphism information content value of 0.431. The development of genic-SSR markers in this study is indeed timely to provide useful markers for functional and population genetic studies of the cynomolgus macaque and other related non-human primate species.
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Bases de Datos Genéticas , Macaca fascicularis/genética , Repeticiones de Microsatélite/genética , Transcriptoma/genética , Animales , Análisis de Datos , Marcadores Genéticos , Anotación de Secuencia Molecular , Motivos de Nucleótidos/genética , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Type II odontoid fracture is a highly morbid injury among octogenarians, with 41% 1-year mortality. Our objective was to assess long-term fusion, complication, and survival rates. METHODS: Retrospective review of prospective trauma registry and blinded review of follow-up radiographs. RESULTS: Follow-up cohort included 94 nonoperative and 17 operative patients (median, 52 and 79 months). The operative group had significantly higher rates of repeated surgery for primary treatment failure or complication (1% vs. 18%; P = 0.01) and dysphagia, aspiration events, or tracheostomy (29% vs. 78%, P = 0.002; 6% vs. 30%, P = 0.04; 1% vs. 18%, P = 0.01). Three-year all-cause mortalities were 71% and 76%, respectively (P = 0.78). No delayed myelopathy was observed. One-year postinjury radiographs were available for 13 and 6 patients in the nonoperative and operative groups (P = 0.9); bony union was observed in 3 and 5 patients (23% vs. 83%; P = 0.04). Retrolisthesis greater than 2 mm was observed in 2 and 1 patients (15% vs. 17%; P = 1.0). Two patients in the operative group underwent repeated surgery for primary treatment failure. Dysphagia was diagnosed in 3 and 5 operative patients (23% vs. 83%; P = 0.04), whereas aspiration events occurred in 0 and 3 patients (0% vs. 50%; P = 0.02). Three-year mortalities in this cohort were 38% and 67% (P = 0.35). CONCLUSIONS: Radiographic union is significantly associated with operative management, but the corresponding clinical benefit is unclear. Complications were significantly more common after surgery. Long-term survival in octogenarians following type II odontoid fracture is poor, independent of management. Frequent complications without a proven survival benefit suggest that most patients are better managed conservatively.
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Apófisis Odontoides/lesiones , Fracturas de la Columna Vertebral/mortalidad , Fracturas de la Columna Vertebral/terapia , Anciano de 80 o más Años , Trastornos de Deglución/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Apófisis Odontoides/diagnóstico por imagen , Apófisis Odontoides/cirugía , Complicaciones Posoperatorias/mortalidad , Estudios Prospectivos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Unicentric Castleman disease is a rare condition of lymphoid hyperplasia, of which only 15% of cases occur in the abdomen. We report a 66-year-old man who presented with complaints of abdominal pain. Computed tomography scans revealed nephrolithiasis and a homogeneous calcified mass between the pancreas and stomach and several para-pancreatic nodes. Direct visualization during exploratory laparotomy revealed a mass on the lesser curvature of the stomach. Pyloromyotomy and mass resection were performed. Biopsy showed reactive lymphoid hyperplasia consistent with the hyaline vascular variant of Castleman disease.
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OBJECTIVE Type II odontoid fracture is a common injury among elderly patients, particularly given their predisposition toward low-energy falls. Previous studies have demonstrated a survival advantage following early surgery among patients older than 65 years, yet octogenarians represent a medically distinct and rapidly growing population. The authors compared operative and nonoperative management in patients older than 79 years. METHODS A single-center prospectively maintained trauma database was reviewed using ICD-9 codes to identify octogenarians with C-2 cervical fractures between 1998 and 2014. Cervical CT images were independently reviewed by blinded neurosurgeons to confirm a Type II fracture pattern. Prospectively recorded outcomes included Glasgow Coma Scale (GCS) score, Abbreviated Injury Scale (AIS) score, Injury Severity Score (ISS), additional cervical fracture, and cord injury. Primary end points were mortality at 30 days and at 1 year. Statistical tests included the Student t-test, chi-square test, Fisher's exact test, Kaplan-Meier test, and Cox proportional hazard. RESULTS A total of 111 patients met inclusion criteria (94 nonoperative and 17 operative [15 posterior and 2 anterior]). Mortality data were available for 100% of patients. The mean age was 87 years (range 80-104 years). Additional cervical fracture, spinal cord injury, GCS score, AIS score, and ISS were not associated with either management strategy at the time of presentation. The mean time to death or last follow-up was 22 months (range 0-129 months) and was nonsignificant between operative and nonoperative groups (p = 0.3). Overall mortality was 13% in-hospital, 26% at 30 days, and 41% at 1 year. Nonoperative and operative mortality rates were not significant at any time point (12% vs 18%, p = 0.5 [in-hospital]; 27% vs 24%, p = 0.8 [30-day]; and 41% vs 41%, p = 1.0 [1-year]). Kaplan-Meier analysis did not demonstrate a survival advantage for either management strategy. Spinal cord injury, GCS score, AIS score, and ISS were significantly associated with 30-day and 1-year mortality; however, Cox modeling was not significant for any variable. Additional cervical fracture was not associated with increased mortality. The rate of nonhome disposition was not significant between the groups. CONCLUSIONS Type II odontoid fracture is associated with high morbidity among octogenarians, with 41% 1-year mortality independent of intervention-a dramatic decrease from actuarial survival rates for all 80-, 90-, and 100-year-old Americans. Poor outcome is associated with spinal cord injury, GCS score, AIS score, and ISS.
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Apófisis Odontoides/lesiones , Fracturas de la Columna Vertebral/terapia , Accidentes por Caídas/mortalidad , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Escala de Coma de Glasgow , Humanos , Puntaje de Gravedad del Traumatismo , Estimación de Kaplan-Meier , Masculino , Apófisis Odontoides/diagnóstico por imagen , Apófisis Odontoides/cirugía , Estudios Prospectivos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/mortalidad , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/mortalidad , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: We undertook a multidimensional clinical genomics study of children and adolescent young adults with relapsed and refractory cancers to determine the feasibility of genome-guided precision therapy. EXPERIMENTAL DESIGN: Patients with non-central nervous system solid tumors underwent a combination of whole exome sequencing (WES), whole transcriptome sequencing (WTS), and high-density single-nucleotide polymorphism array analysis of the tumor, with WES of matched germline DNA. Clinically actionable alterations were identified as a reportable germline mutation, a diagnosis change, or a somatic event (including a single nucleotide variant, an indel, an amplification, a deletion, or a fusion gene), which could be targeted with drugs in existing clinical trials or with FDA-approved drugs. RESULTS: Fifty-nine patients in 20 diagnostic categories were enrolled from 2010 to 2014. Ages ranged from 7 months to 25 years old. Seventy-three percent of the patients had prior chemotherapy, and the tumors from these patients with relapsed or refractory cancers had a higher mutational burden than that reported in the literature. Thirty patients (51% of total) had clinically actionable mutations, of which 24 (41%) had a mutation that was currently targetable in a clinical trial setting, 4 patients (7%) had a change in diagnosis, and 7 patients (12%) had a reportable germline mutation. CONCLUSIONS: We found a remarkably high number of clinically actionable mutations in 51% of the patients, and 12% with significant germline mutations. We demonstrated the clinical feasibility of next-generation sequencing in a diverse population of relapsed and refractory pediatric solid tumors. Clin Cancer Res; 22(15); 3810-20. ©2016 AACR.
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Genómica , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisión , Adolescente , Adulto , Biomarcadores de Tumor , Niño , Preescolar , Resistencia a Antineoplásicos , Femenino , Genómica/métodos , Mutación de Línea Germinal , Humanos , Lactante , Masculino , Terapia Molecular Dirigida , Mutación , Neoplasias/diagnóstico , Polimorfismo de Nucleótido Simple , Medicina de Precisión/métodos , Recurrencia , Secuenciación del Exoma , Adulto JovenRESUMEN
Heterocyclic amines (HAAs) and polycyclic hydrocarbons are suspected colorectal cancer (CRC) carcinogens that are found in well-done meat. They require metabolic activation by phase I enzymes, such as the smoking-inducible CYP1A isoenzymes. N-acetyltransferase 2 (NAT2) also play a role in the further activation of HAAs. We conducted a population-based case-control study in Hawaii to test the associations of preference for well-done red meat and HAA intake with colon and rectal cancers, as well as the modifying effects of NAT2 and CYP1A2. We interviewed 727 Japanese, Caucasian or Native Hawaiian cases and 727 controls matched on sex, age, and ethnicity. HAA intake was estimated based on consumption of meat and fish for each of several cooking methods and doneness levels. A subgroup of 349 cases and 467 controls was phenotyped for CYP1A2 by a caffeine test. We found that preference for well-done red meat was associated with a 8.8-fold increased risk of CRC (95% CI: 1.7-44.9) among ever-smokers with the NAT2 and CYP1A2 rapid phenotypes, compared to ever-smokers with low NAT2 and CYP1A2 activities and who preferred their red meat rare or medium. A dose-dependent association was also found between the HAA intake estimates and male rectal cancer, with a two- to three-fold increase in risk from the low (T(1)) to high (T(3)) tertile of intake for each HAA. This association was strongest for MeIQx. HAA intake was not associated with male colon cancer or colon or rectal cancer in women. These data provide support to the hypothesis that exposure to pyrolysis products through consumption of well-done meat increases the risk of CRC, particularly in individuals who smoke and are genetically susceptible (as determined by a rapid phenotype for both NAT2 and CYP1A2). An attempt to examine the risk associated with specific HAAs suggested that the main HAAs increase risk of rectal cancer in men and that they do not appreciably affect risk of rectal cancer in women or of colon cancer in either sex.
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Arilamina N-Acetiltransferasa/genética , Neoplasias Colorrectales/etiología , Citocromo P-450 CYP1A2/genética , Predisposición Genética a la Enfermedad , Carne , Fumar/efectos adversos , Adolescente , Arilamina N-Acetiltransferasa/metabolismo , Estudios de Casos y Controles , Neoplasias Colorrectales/genética , Culinaria , Citocromo P-450 CYP1A2/metabolismo , Dieta , Inducción Enzimática , Femenino , Genotipo , Hawaii , Humanos , Linfocitos/fisiología , Masculino , Fenotipo , Sistema de Registros , Factores de RiesgoRESUMEN
The advent of human assisted reproductive technology (ART) has engendered much legal and ethical debate. This article examines the evolution of regulation in ART in the USA and discusses the impetus for, and repercussions of, the Human Fertilisation and Embryology Authority in the UK. Key differences in government legislation between the UK and USA have driven the evolution of a distinct regulatory body that oversees ART in the USA. The National Advisory Board on Ethics in Reproduction (NABER) serves as an unofficial advisory body that addresses ethical issues in reproduction. The Society for Assisted Reproductive Technology (SART) maintains a registry that collects, reports and verifies data for individual ART clinics. Clinic-specific success rates are readily available through annual reports published through a collaboration of SART, the American Society of Reproductive Medicine (ASRM), the Center for Disease Control (CDC), and the National Infertility Association (RESOLVE). The ASRM has assumed a strong advisory role in addressing ethical issues and practice guidelines in assisted reproduction. Thus, although there is no central body to regulate ART in the USA, basic legislation, standards and guidelines that drive the provision of these services do exist in the USA.
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Técnicas Reproductivas Asistidas/historia , Técnicas Reproductivas Asistidas/legislación & jurisprudencia , Femenino , Historia del Siglo XX , Humanos , Infertilidad/terapia , Guías de Práctica Clínica como Asunto , Embarazo , Sistema de Registros , Técnicas Reproductivas Asistidas/ética , Técnicas Reproductivas Asistidas/estadística & datos numéricos , Resultado del Tratamiento , Reino Unido , Estados UnidosRESUMEN
OBJECTIVE: To determine the impact of ovary-secreted products on adrenocortical function in women with PCOS by studying the adrenocortical response to acute adrenocorticotropic-stimulating hormone (ACTH) stimulation before and after bilateral oophorectomy. DESIGN: Prospective study. SETTING: Tertiary care medical center. PATIENT(S): Fourteen women with PCOS, scheduled for bilateral oophorectomy for benign indications, on postoperative transdermal estradiol (E(2)). INTERVENTION(S): Physical examination, blood sampling before and after oophorectomy, measurement of hormone levels; assessment of basal (Steroid(0)), maximum stimulated (Steroid(60)), and net increment (ΔSteroid) levels of androstenedione (A4), dehydroepiandrosterone (DHEA), and cortisol (F) before and after ACTH 1-24 stimulation. MAIN OUTCOME MEASURE(S): Preoperative and postoperative basal and ACTH (1-24) stimulated hormone levels. RESULT(S): Total testosterone, free testosterone, and estrone levels decreased, and follicle-stimulating hormone levels statistically significantly increased after oophorectomy. No statistically significant differences in E(2), DHEA sulfate (DHEAS), or sex hormone-binding globulin levels were detected. Basal and ACTH-stimulated A4 levels statistically significantly decreased after oophorectomy, and ΔA4 was statistically significantly increased. No statistically significant differences in DHEA(0), DHEA(60), or F(0) levels were detected. The F(60) and ΔF levels tended to increase after oophorectomy, but the differences did not reach statistical significance. CONCLUSION(S): Ovarian factors do not appear to contribute significantly to the adrenocortical dysfunction of PCOS.
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Enfermedades de la Corteza Suprarrenal/diagnóstico , Enfermedades de la Corteza Suprarrenal/etiología , Ovariectomía/efectos adversos , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/cirugía , Adulto , Femenino , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Accurate electrocardiographic (ECG) differentiation of ventricular tachycardia (VT) from supraventricular tachycardia with aberrancy (SVT-A) on ECG is key to therapeutic decision-making in the emergency department (ED) setting. OBJECTIVE: The goal of this study was to test the accuracy and agreement of emergency medicine residents to differentiate VT from SVT-A using the Vereckei criteria. METHODS: Six emergency medicine residents volunteered to participate in the review of 114 ECGs from 86 patients with a diagnosis of either VT or SVT-A based on an electrophysiology study. The resident reviewers initially read 12-lead ECGs blinded to clinical information, and then one week later reviewed a subset of the same 12-lead ECGs unblinded to clinical information. RESULTS: One reviewer was excluded for failing to follow study protocol and one reviewer was excluded for reviewing less than 50 blinded ECGs. The remaining four reviewers each read 114 common ECGs blinded to clinical data and their diagnostic accuracy for VT was 74% (sensitivity 70%, specificity 80%), 75% (sensitivity 76%, specificity 73%), 61% (sensitivity 81%, specificity 25%), and 68% (sensitivity 84%, specificity 40%). The intraclass correlation coefficient (ICC) was 0.31 (95% CI 0.22-0.42). Eliminating two of the four reviewers who left a disproportionately high number of ECGs unclassified resulted in an increase in overall mean diagnostic accuracy (70-74%) and agreement (0.31-0.50) in the two remaining reviewers. Three reviewers read 45 common ECGs unblinded to clinical information and had accuracies for VT 93%, 93% and 78%. CONCLUSION: The new single lead Vereckei criteria, when applied by emergency medicine residents achieved only fair-to-good individual accuracy and moderate agreement. The addition of clinical information resulted in substantial improvement in test characteristics. Further improvements (accuracy and simplification) of algorithms for differentiating VT from SVT-A would be helpful prior to clinical implementation.
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Electrocardiografía/métodos , Electrocardiografía/normas , Medicina de Emergencia/métodos , Internado y Residencia , Taquicardia Supraventricular/diagnóstico , Taquicardia Ventricular/diagnóstico , Diagnóstico Diferencial , Humanos , Variaciones Dependientes del Observador , Sensibilidad y Especificidad , Taquicardia Supraventricular/epidemiología , Taquicardia Ventricular/epidemiologíaRESUMEN
The floor plate, an essential ventral midline organizing center that produces the morphogen Shh, has distinct properties along the neuraxis. The neurogenic potential of the floor plate and its underlying mechanisms remain unknown. Using Shh as a driver for lineage analysis, we found that the mouse midbrain, but not the hindbrain, floor plate is neurogenic, giving rise to dopamine (DA) neurons. Distinct spatiotemporal Shh and Wnt expression may distinguish the neurogenetic potential of these structures. We discovered an inhibitory role for Shh: removal of Shh resulted in neurogenesis from the hindbrain midline and, conversely, high doses of Shh inhibited proliferation and DA neuron production in midbrain cultures. We found that Wnt/beta-catenin signaling is necessary and sufficient for antagonizing Shh, DA progenitor marker induction and promotion of dopaminergic neurogenesis. These findings demonstrate how the dynamic interplay of canonical Wnt/beta-catenin signaling and Shh may orchestrate floor plate neurogenesis or a lack thereof.
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Proteínas Hedgehog/metabolismo , Mesencéfalo/fisiología , Neurogénesis/fisiología , Neuronas/fisiología , Nicho de Células Madre/fisiología , Proteínas Wnt/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Células Cultivadas , Femenino , Regulación del Desarrollo de la Expresión Génica , Proteínas Hedgehog/genética , Factor Nuclear 3-beta del Hepatocito/metabolismo , Proteínas de Homeodominio/metabolismo , Proteínas con Homeodominio LIM , Masculino , Mesencéfalo/citología , Mesencéfalo/embriología , Ratones , Ratones Noqueados , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuronas/citología , Factores de Transcripción Otx/metabolismo , Embarazo , Rombencéfalo/citología , Rombencéfalo/embriología , Rombencéfalo/fisiología , Transducción de Señal/fisiología , Nicho de Células Madre/citología , Células Madre/citología , Células Madre/fisiología , Factores de Transcripción/metabolismo , beta Catenina/metabolismoRESUMEN
OBJECTIVE: To test the hypothesis that an abnormality in glycogen synthase kinase-3 (GSK3) is a pathogenic factor in polycystic ovary syndrome (PCOS). DESIGN: Prospective experimental study (adipocytes). SETTING: Tertiary-care academic medical center and teaching hospital. PATIENT(S): Twenty patients with PCOS and 21 healthy control women. INTERVENTION(S): Blood sampling, physical exam, biopsy of SC lower abdominal fat. MAIN OUTCOME MEASURE(S): Glucose transport and protein levels and phosphorylation state of glycogen synthase kinase (GSK)-3alpha and GSK3beta in adipocytes; assessment of GSK3beta activity. RESULT(S): Basal protein levels of glycogen synthase kinase (GSK3alpha and GSK3beta) did not differ between control women and women with PCOS, nor did basal or insulin-stimulated levels of serine phosphorylated GSK3alpha. However, in adipocytes of women with PCOS, insulin stimulation was not associated with increased serine phosphorylation of GSK3beta, in contrast to the case of control women. Tyrosine phosphorylation of GSK3beta also was higher in women with PCOS, compared with in control women. Consistent with the phosphorylation data, GSK3beta activity was elevated in PCOS adipocytes. CONCLUSION(S): These data suggest that GSK3beta is hyperactivated and resistant to down-regulation by insulin in PCOS. By using physiologic approaches, we demonstrated that abnormal GSK3beta regulation is a potential mechanism for the insulin resistance that is seen in some women with PCOS, which may contribute to their development of the syndrome.