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AIMS: To assess if advanced characterization of serum glycoprotein and lipoprotein profile, measured by proton nuclear magnetic resonance spectroscopy (1H-NMRS) improves a predictive clinical model of cardioautonomic neuropathy (CAN) in subjects with type 1 diabetes (T1D). METHODS: Cross-sectional study (ClinicalTrials.gov Identifier: NCT04950634). CAN was diagnosed using Ewing's score. Advanced characterization of macromolecular complexes including glycoprotein and lipoprotein profiles in serum samples were measured by 1H-NMRS. We addressed the relationships between these biomarkers and CAN using correlation and regression analyses. Diagnostic performance was assessed by analyzing their areas under the receiver operating characteristic curves (AUCROC). RESULTS: Three hundred and twenty-three patients were included (46% female, mean age and duration of diabetes of 41 ± 13 years and 19 ± 11 years, respectively). The overall prevalence of CAN was 28% [95% confidence interval (95%CI): 23; 33]. Glycoproteins such as N-acetylglucosamine/galactosamine and sialic acid showed strong correlations with inflammatory markers such as high-sensitive C-reactive protein, fibrinogen, IL-10, IL-6, and TNF-α. On the contrary, we did not find any association between the former and CAN. A stepwise binary logistic regression model (R2 = 0.078; P = 0.003) retained intermediate-density lipoprotein-triglycerides (IDL-TG) [ß:0.082 (95%CI: 0.005; 0.160); P = 0.039], high-density lipoprotein-triglycerides (HDL-TGL)/HDL-Cholesterol [ß:3.633 (95%CI: 0.873; 6.394); P = 0.010], and large-HDL particle number [ß: 3.710 (95%CI: 0.677; 6.744); P = 0.001] as statistically significant determinants of CAN. Adding these lipoprotein particles to a clinical prediction model of CAN that included age, duration of diabetes, and A1c enhanced its diagnostic performance, improving AUCROC from 0.546 (95%CI: 0.404; 0.688) to 0.728 (95%CI: 0.616; 0.840). CONCLUSIONS: When added to clinical variables, 1H-NMRS-lipoprotein particle profiles may be helpful to identify those patients with T1D at risk of CAN.
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Biomarcadores , Diabetes Mellitus Tipo 1 , Lipoproteínas , Espectroscopía de Protones por Resonancia Magnética , Humanos , Femenino , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/sangre , Masculino , Adulto , Estudios Transversales , Lipoproteínas/sangre , Biomarcadores/sangre , Espectroscopía de Protones por Resonancia Magnética/métodos , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/epidemiología , Persona de Mediana Edad , Pronóstico , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/etiología , Enfermedades del Sistema Nervioso Autónomo/sangreRESUMEN
PURPOSE: Evidence-based guidelines for the management of polycystic ovary syndrome (PCOS) recommend clinical laboratories use liquid chromatography-tandem mass spectrometry (LC-MS/MS) for diagnosing biochemical hyperandrogenism. However, automated immunoassays are still mostly used in routine laboratories worldwide. Another hurdle for PCOS phenotyping in the clinical setting is ultrasound assessment of polycystic ovarian morphology. We address the impact of using state-of-the-art (LC-MS/MS) and of an anti-müllerian hormone (AMH) assay on the diagnosis of PCOS in routine practice. METHODS: In a cross-sectional study, we included 359 premenopausal women consecutively evaluated because of symptoms of functional androgen excess or hyperandrogenemia, and finally diagnosed with PCOS. Patients were submitted to routine phenotyping based on serum androgen measurements by immunoassays and an ovarian ultrasound when necessary. Samples of all patients were also assayed by LC-MS/MS for hyperandrogenemia and for circulating AMH. RESULTS: The observed agreement between immunoassays and LC-MS/MS in identifying hyperandrogenemia was poor [78.0%; k(95%CI): 0.366 (0.283;0.449)]. The observed agreement between ultrasound and increased AMH was 27.3% [(95%CI): 0.060 (0.005; 0.115)]. Using LC-MS/MS changed PCOS phenotypes in 60(15.8%) patients. Fifty-two (18.3%) individuals with hyperandrogenemia by routine immunoassays no longer presented with androgen excess by LC-MS/MS. Overall diagnostic agreement between routine assessment using immunoassays and ultrasound and that derived from LC-MS/MS and the addition of AMH to US was moderate [weighted κ (linear weights): 0.512 (0.416;0.608)]. CONCLUSIONS: Immunoassays used in routine practice are unacceptably inaccurate for phenotyping women with PCOS. Our data cast some doubts upon the interchangeability of serum AMH and ultrasound examination for the diagnosis of PCOS.
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Intensive care medicine in Chile is still in its dawn. It has experienced a progressive growth in the last decade, but continues to be weak. Although investments in the discipline have increased fivefold, there is still a severe deficiency of intensive care specialists. This issue will represent a serious problem in the near future. The Ministry of Health gathered an expert committee to study the problem and propose solutions for the future development of the discipline.
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Cuidados Críticos , Educación de Postgrado en Medicina , Programas de Gobierno/educación , ChileRESUMEN
The Insula Obesity Center has been treating extremely obese adolescents and young adults since 1992. Various programs ranging from 2-9 months' duration are offered. The mean BMI at admission has been increasing continuously and is presently 41.5 kg/m(2) with occasional extremes over 80 kg/m(2). Obesity comorbidities are common. A mean weight reduction of 1.3 kg/week is achieved during a mean duration of treatment of 4.7 months. Follow-up in residential support groups is offered for up to 2 years for selected patients with special challenges such as lack of family support.
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Obesidad Mórbida/terapia , Adolescente , Alemania , Humanos , Resultado del Tratamiento , Adulto JovenRESUMEN
Invasive infections by Candida strains are a relevant pathology in critically ill patients. Candida should be considered where a high risk of infection is present for a critical early diagnosis. Despite the incorporation of new drugs in the therapeutic armamentarium over the last decade, mortality remains high. The key in improving clinical outcomes of these patients are the use of early effective therapies that offer coverage against different strains of Candida: C. albicans and non-albicans. Recent international guidelines suggest empiric therapy with echinocandins in suspected invasive candidiasis in this patient population. This group of drugs adequately documented clinical efficacy and safe use in these patients. The emergence of new echinocandins could improve access to these drugs by reducing their cost.
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Candidiasis Invasiva , Adulto , Antifúngicos/uso terapéutico , Candidiasis Invasiva/diagnóstico , Candidiasis Invasiva/tratamiento farmacológico , Candidiasis Invasiva/epidemiología , Enfermedad Crítica , Humanos , Unidades de Cuidados Intensivos , Factores de RiesgoRESUMEN
INTRODUCTION: Although sexually active US adults wanting to prevent pregnancy have a wide variety of birth control methods readily available, there is little research that documents the contraceptive choices of rural adults in comparison to urban adults. This study compared the contraceptive choices of rural with urban adults. The comparative analysis joins the recent dialog in population health focused on assessing health related differences to detect if these are indicative of rural health disparities. DESIGN: This was a cross-sectional study analyzing 2004 Behavioral Risk Factor Surveillance Survey (BRFSS) data. Place of residence was ascertained by re-coding the state/county FIPS code as either urban or rural, based on 2003 Rural-Urban Continuum Codes from the US Office of Management and Budget (setting: US households; participants: US adults 18-55 years). MAIN OUTCOME MEASURES: characteristics and contraceptive method choice of rural adults using birth control. RESULTS: A multivariate regression model performed with 'use of birth control' as the dependent variable yielded that rural in comparison with urban adults 18-55 years were more likely to use female or male sterilization, non-injectable and injectable hormones for birth control. They were less likely to use: condoms, a diaphragm or NuvaRing, emergency contraception, withdrawal or rhythm methods. Additionally, in comparison with urban adults, rural persons younger than 35 years, those who had children younger than 18 years living with them, those who were partnered, males and those living in households with an income of less than US$35,000 were more likely to report using some form of contraception. CONCLUSION: There were differences in the contraception choices of urban and rural adults. How much primary care provider preferences explains the differences is not known and bears further exploration. These results should prove useful to healthcare providers as well as public health family planning programs.
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Anticoncepción/métodos , Adolescente , Adulto , Sistema de Vigilancia de Factor de Riesgo Conductual , Conducta de Elección , Estudios Transversales , Composición Familiar , Femenino , Accesibilidad a los Servicios de Salud , Humanos , Seguro de Salud/economía , Seguro de Salud/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Población Rural/estadística & datos numéricos , Factores Socioeconómicos , Estados Unidos , Población Urbana/estadística & datos numéricos , Adulto JovenRESUMEN
We have previously found that, following myocardial ischemia/reperfusion injury, isolated hearts from bax gene knockout mice [Bax(-/-)] exhibited higher cardioprotection than the wild-type. We here explore the effect of Bax(-/-), following myocardial infarction (MI) in vivo. Homozygotic Bax(-/-) and matched wild-type were studied. Mice underwent surgical ligation of the left anterior descending coronary artery (LAD). The progressive increase in left-ventricular end diastolic diameter, end systolic diameter, in Bax(-/-) was significantly smaller than in Bax(+/+) at 28 d following MI (p < 0.03) as seen by echocardiography. Concomitantly, fractional shortening was higher (35 +/- 4.1% and 27 +/- 2.5%, p < 0.001) and infarct size was smaller in Bax(-/-) compared to the wild-type at 28 days following MI (24 +/- 3.7 % and 37 +/- 3.3%, p < 0.001). Creatine kinase and lactate dehydrogenase release in serum were lower in Bax(-/-) than in Bax(+/+) 24 h following MI. Caspase 3 activity was elevated at 2 h after MI only in the wild-type, but reduced to baseline values at 1 and 28 d post-MI. Bax knockout mice hearts demonstrated reduced infarct size and improved myocardial function following permanent coronary artery occlusion. The Bax gene appears to play a significant role in the post-MI response that should be further investigated.
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Infarto del Miocardio/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Animales , Apoptosis , Peso Corporal , Caspasas/metabolismo , Ecocardiografía/métodos , Femenino , Heterocigoto , Homocigoto , Masculino , Ratones , Ratones Noqueados , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Miocardio/patología , Factores de TiempoRESUMEN
Resumen La palabra placebo ha sido usada, indistintamente, para referir a una sustancia o procedimiento que es "inerte" ("placebo") y al efecto que ocurre como consecuencia de la administración de un placebo ("efecto placebo"). El efecto placebo es un fenómeno psicobiológico que ha sido explicado desde el conductismo (condicionamiento clásico), desde fenómenos preconscientes (expectativas o "efecto placebo clásico"), desde el cognitivismo (disonancia cognitiva) y también a nivel neurobiológico. No obstante, los ensayos clínicos abiertos que verifican la respuesta a placebo desafían el mecanismo de la expectativa, dando lugar al análisis bayesiano, que integra sensaciones, experiencias, predicciones y claves del contexto; biológicamente, el efecto placebo no es inerte. Por tanto, el placebo ocupa un lugar relevante en la práctica clínica y en la investigación biomédica. Se realizó una búsqueda sistemática sobre placebo y otorrinolaringología en las bases de datos PubMed/Medline, SciELO y Cochrane Library. Se incluyeron estudios primarios y revisiones sistemáticas de la literatura. En cuanto a intervenciones placebo, la literatura publicada indica mejorías significativas en síntomas nasales y calidad de vida en rinitis alérgica (estacional y perenne) y disminución del dolor posoperatorio en amigdalectomía. En la enfermedad de Méniere, las intervenciones placebo son comparables a las de uso habitual, incluyendo las quirúrgicas. No se encontraron ensayos clínicos abiertos en otorrinolaringología ni evidencia sobre otras patologías del área. Las intervenciones y el efecto placebo abren un campo de investigación y desarrollo en otorrinolaringología que desafía la comprensión actual de las patologías, su funcionamiento, su tratamiento y la relación terapéutica.
Abstract The word placebo has been used interchangeably to refer to a substance or procedure that is "inert" ("placebo") and the effect that occurs as a consequence of its administration ("placebo effect"). The placebo effect corresponds to a psychobiological phenomenon that has been explained from behaviorism (classical conditioning), from preconscious phenomena (expectations or "classical placebo effect"), from cognitivism (cognitive dissonance) and at the neurobiological level as well. Nevertheless, some open-label trials that verify the response to placebo challenge the expectation mechanism, giving rise to Bayesian analysis, which integrates sensations, experiences, predictions and context clues; therefore, biologically, the placebo effect is not inert. The placebo has a relevant place both in clinical practice and in biomedical research. We conducted a systematic search on placebo and otolaryngology in PubMed/Medline, SciELO and Cochrane Library databases. We included primary studies and systematic reviews. Regarding placebo interventions, the available literature points out significant improvements in nasal symptoms and quality of life in allergic rhinitis (seasonal and perennial) and a decrease in post-tonsillectomy pain. In Méniére's disease, placebo interventions have demonstrated to be comparable to treatment-as-usual, including surgical interventions. No open-label clinical trials were found in otolaryngology, as well as no evidence on other diseases in the area. Placebo interventions and their effects open a field of research and development in otolaryngology, challenging the current understanding of pathologies, their functioning, their treatment and the therapeutic relationship.
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Humanos , Otolaringología , Efecto Placebo , Dolor Postoperatorio , Tonsilectomía , Rinitis Alérgica , Enfermedad de MeniereRESUMEN
The Montgomery T-tube is used as a combined tracheal stent and airway after laryngotracheoplasty, to keep the lumen open and prevent mucosal laceration from scarring. It is valuable in the management of upper and mid-tracheal lesions, while invaluable in long and multisegmental stenting lesions. Numerical simulations based on real-patient-tracheal geometry, experimental tissue characterization, and previous numerical estimation of the physiological swallowing force are performed to estimate the consequences of Montgomery T-tube implantation on swallowing and assisted ventilation: structural analysis of swallowing is performed to evaluate patient swallowing capacity, and computational fluid dynamics simulation is carried out to analyze related mechanical ventilation. With an inserted Montgomery T-tube, vertical displacement (Z-axis) reaches 8.01 mm, whereas in the Y-axis, it reaches 6.63 mm. The maximal principal stress obtained during swallowing was 1.6 MPa surrounding the hole and in the upper contact with the tracheal wall. Fluid flow simulation of the mechanical ventilation revealed positive pressure for both inhalation and exhalation, being higher for inspiration. The muscular deflections, considerable during normal breathing, are nonphysiological, and this aspect results in a constant overload of the tracheal muscle. During swallowing, the trachea ascends producing a nonhomogeneous elongation. This movement can be compromised when prosthesis is inserted, which explains the high incidence of glottis close inefficiency. Fluid simulations showed that nonphysiological pressure is established inside the trachea due to mechanical ventilation. This may lead to an overload of the tracheal muscle, explaining several related problems as muscle thinning or decrease in contractile function.
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Trastornos de Deglución/fisiopatología , Modelos Biológicos , Presión , Respiración Artificial/métodos , Stents , Humanos , Músculo Liso/fisiología , Implantación de Prótesis , Tráquea/fisiologíaRESUMEN
We describe a girl who presented at the age of 11 years with short stature. She had female external genitalia and some clinical features of Turner syndrome. At laparotomy a uterus and Fallopian tubes and small gonad-like tissue masses in the region of the Fallopian fimbria were found. The tissue masses were removed and histological examination revealed no organized testicular or ovarian morphology. Remnants of Fallopian tubes, epididymis, and clusters of Leydig cells were seen but no Sertoli cells were found. Endocrine studies showed levels of sex hormones consistent with primary gonadal failure. G-banding analysis of 16 blood lymphocytes revealed the karyotype 46,X,dicY(q11.2) in all cells. Varying proportions of X and Y centromeres in blood lymphocytes, skin fibroblasts, and in the incompletely formed Wolffian and Müllerian duct derivatives were demonstrated by FISH. Molecular studies confirmed the absence of most of the long arm of the Y chromosome and an intact short arm. The SRY gene was shown to be present, but we presume that due to the mosaicism the dose was insufficient to allow normal testicular development.
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Cromosomas Humanos Par 11/genética , Mosaicismo/genética , Translocación Genética/genética , Cromosoma X/genética , Cromosoma Y/genética , Niño , Análisis Citogenético/métodos , Femenino , Humanos , Hibridación Fluorescente in Situ/métodos , FenotipoRESUMEN
In the past two decades, transplantation has become a preferred modality of treatment of end-stage failure of vital organs. Currently, with the significant improvement in short-term graft survival rates, the main effort is concentrated on prolonging the functional life span of transplanted organs. One of the theories which were put forward to explain the progressive deterioration of transplant function was that of replicative senescence. Senescence of an organ or tissue results from age and/or environmental stress-dependant modification of cellular function. With time, the accumulation of cellular alterations may lead to deleterious effects in various organs and tissues and adversely affect transplants. In this article we are reviewing the candidate mechanisms of senescence such as telomere shortening, genetic regulation and environmental-'toxic' factors and are examining the implications of the theory of replicative senescence for organ allograft. We are also presenting our experiments with renal ischemia/reperfusion in rat serving as a model of kidney transplantation, where baseline kidney telomere length and novel marker of cellular senescence--senescence associated beta-Galactosidase (SA-Gal) expression in tissue served as markers. For the first time in vivo, we were able to show that with aging of the animals the amount of senescent cells in kidney tissue was increasing, while the average renal tissue telomere length was decreasing. The degree of tissue senescence, as determined by amount of SA-Gal positively stained cells, was inversely correlated with the recovery of the kidney function after ischemia/reperfusion injury. These results confirm the theory of replicative senescence in organ ischemia for the first time in vivo, and quantitatively validate the direct correlation between the amount of senescent cells in the organ and its susceptibility to ischemic injury. We conclude that recent advances in study of the cellular basis of senescence, in vitro and especially in vivo, may hold clues to the understanding of events which could be implicated in the damage or protection of organ allografts.
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Senescencia Celular , Trasplante de Riñón/efectos adversos , Riñón/patología , Animales , Genes p16/fisiología , Genes p53/fisiología , Humanos , Inmunosupresores/toxicidad , Riñón/efectos de los fármacos , Riñón/fisiología , TelómeroRESUMEN
Rhabdomyosarcoma may be divided into three subtypes--embryonal, alveolar, and undifferentiated sarcoma--which can be distinguished by molecular analysis. The authors applied reverse transcriptase-polymerase chain reaction analysis (RT-PCR) to analyze tumor samples from 14 children with rhabdomyosarcoma for the presence of the chimeric PAX3-FKHR transcript resulting from the translocation t(2;13)(q35,q14). Both fresh and paraffin-embedded tissues were used. In only nine specimens was the RNA intact for the analysis. The chimeric transcript was identified in seven samples: four alveolar type, one embryonal type, and two undifferentiated sarcoma. Histologic review was performed in the three samples with discordance between the molecular and histologic findings. A sample from a patient with a diagnosis of embryonal rhabdomyosarcoma on presentation and expression of PAX3-FKHR fusion transcript yielded a small focus of alveolar rhabdomyosarcoma and was reclassified as alveolar rhabdomyosarcoma. One of the samples from a patient with undifferentiated sarcoma was redefined as alveolar subtype; the diagnosis of the second undifferentiated sarcoma remained unchanged, in accordance with the histologic diagnosis. These findings further support the recommendation that molecular analysis be included in the diagnostic workup of childhood small round cell tumors to reach a more accurate diagnosis for tailoring of specific treatment.
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ADN de Neoplasias/análisis , Proteínas de Unión al ADN/genética , Proteínas de Neoplasias/genética , Rabdomiosarcoma Alveolar/diagnóstico , Neoplasias de los Tejidos Blandos/diagnóstico , Factores de Transcripción/genética , Adolescente , Adulto , Fusión Artificial Génica , Niño , Preescolar , Femenino , Proteína Forkhead Box O1 , Factores de Transcripción Forkhead , Humanos , Lactante , Pérdida de Heterocigocidad , Masculino , Factor de Transcripción PAX3 , Factores de Transcripción Paired Box , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rabdomiosarcoma Alveolar/genética , Neoplasias de los Tejidos Blandos/genética , Resultado del TratamientoRESUMEN
BACKGROUND: Mitral annular calcification is a common echocardiographic finding. Caseous calcification is a rare variant seen as a large mass with echolucencies that resembles a tumor, occasionally resulting in exploratory cardiotomy. The aim of this study was to assess the prevalence of caseous calcification of the mitral annulus, to evaluate patient characteristics and the echocardiographic variables for diagnosing this entity, and to describe the clinical outcome on follow-up of such patients. METHODS: Caseous calcification was defined as a large, round, echo-dense mass with smooth borders situated in the periannular region, with no acoustic shadowing artifacts and containing central areas of echolucencies resembling liquefaction. Eighteen patients were diagnosed by 2-dimensional echocardiography as having caseous calcification of the mitral annulus. One had calcification of the tricuspid annulus. Nine patients underwent transesophageal echocardiographic studies. RESULTS: A typical finding of a round, sometimes semilunar, large, echo-dense, soft mass with central echolucencies seen on both transthoracic and in particular transesophageal echocardiography, resembling a periannular mass, was demonstrated. The mass was posteriorly located in all mitral patients. Transesophageal echocardiography added limited information. Three patients underwent mitral valve replacement. The operative findings were a solid mass adherent to the posterior portion of the mitral valve. Sectioning revealed a toothpaste-like, white, caseous material. Sixteen (84%) patients were treated conservatively. On follow-up of 3.8 +/- 2.4 years, 4 patients died of unrelated causes. CONCLUSION: The characteristic appearance of a large, soft, echo-dense mass containing central areas of echolucencies resembling liquefaction at the posterior periannular region of the mitral valve on 2D echocardiography is compatible with the diagnosis of caseous abscess. Such a finding should not be confused with a tumor. Transesophageal echocardiography does not appear to contribute to the diagnosis. This rather impressive lesion appears to carry a benign prognosis.
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Calcinosis/diagnóstico por imagen , Estenosis de la Válvula Mitral/diagnóstico por imagen , Válvula Mitral/diagnóstico por imagen , Anciano , Calcinosis/patología , Calcinosis/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/patología , Válvula Mitral/cirugía , Estenosis de la Válvula Mitral/patología , Estenosis de la Válvula Mitral/cirugía , UltrasonografíaRESUMEN
Menopause is a time of anatomic, physiological and psychological changes that often influence in the sexuality of aging female. Being sexual functioning an important aspect of health and well-being, doctors should have an holistic approach reassuring about the possibility of treating the various symptoms. The central nervous system is an important target for sex steroid hormone; estrogen, progestagens and androgens are able to modulate several brain functions, and receptors for gonadal steroids have been identified in several brain areas. Because there is no test that physicians can make to assess sexual function, taking a sexual history is probably the most important aspect in the diagnostic and treatment of sexual problems. Hormonal transition with decreasing levels of estrogen and testosterone produces clinical effects, so women need to make adjustments for this period of life. Testosterone is an important component of female sexuality, and alterations in its circulating levels play an important role in psychological and sexual changes that occur after menopause. This is the reason why the research in identifying women who have a decrease androgen active should be aimed. Treatment may include education about sexuality and medical management of symptoms or problems interfering with sexual activity. Also treatment implications and the diverse aspects that may influence on sexuality in the climacteric years are discussed.
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Menopausia , Sexualidad , Envejecimiento , Antagonistas de Andrógenos/uso terapéutico , Andrógenos/sangre , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Norpregnenos/uso terapéuticoRESUMEN
BACKGROUND: Familial nephritis is a heterogeneous group of disorders caused by several genetic conditions such as Alport syndrome, glomerulonephritic syndromes, and unclassified nephritis without deafness or ocular defects. OBJECTIVES: To describe a family of Iraqi Jewish origin, several of whose members suffer from non-syndromic renal failure without deafness or ocular defects and where transmission is by autosomal dominant inheritance. We present the case histories of four family members and describe the molecular analysis performed in order to seek a possible linkage to one of the genes causing Alport or Alport-like syndromes. METHODS: We investigated all family members over the age of 18 for evidence of renal failure. We also extracted DNA and carried out molecular linkage analysis with polymorphic markers in each of the known loci involved in Alport and Alport-like syndromes. RESULTS: Histology of the renal biopsy specimens showed non-specific findings. Linkage was excluded for all the Alport and Alport-like syndrome loci. CONCLUSIONS: The condition suffered by several members of this family seems to represent a unique autosomal dominant type of progressive hereditary nephritis, characterized by hypertension and progressive renal failure without significant hematuria or proteinuria. The main histological changes are non-specific in the early stage of the disease. Our study rules out all the currently known genes that cause Alport syndrome as being responsible for the basic defect in this type of nephritis.
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Genes Dominantes/genética , Fallo Renal Crónico/etiología , Fallo Renal Crónico/genética , Nefritis Hereditaria/complicaciones , Nefritis Hereditaria/genética , Adolescente , Adulto , Creatinina/sangre , Femenino , Ligamiento Genético/genética , Genotipo , Humanos , Fallo Renal Crónico/patología , Masculino , Nefritis Hereditaria/patología , Linaje , Reacción en Cadena de la Polimerasa , Polimorfismo Genético/genéticaRESUMEN
The application of three-dimensional (3D) biomaterials to facilitate the adhesion, proliferation, and differentiation of cells has been widely studied for tissue engineering purposes. The fabrication methods used to improve the mechanical response of the scaffold produce complex and non regular structures. Apart from the mechanical aspect, the fluid behavior in the inner part of the scaffold should also be considered. Parameters such as permeability (k) or wall shear stress (WSS) are important aspects in the provision of nutrients, the removal of metabolic waste products or the mechanically-induced differentiation of cells attached in the trabecular network of the scaffolds. Experimental measurements of these parameters are not available in all labs. However, fluid parameters should be known prior to other types of experiments. The present work compares an experimental study with a computational fluid dynamics (CFD) methodology to determine the related fluid parameters (k and WSS) of complex non regular poly(L-lactic acid) scaffolds based only on the treatment of microphotographic images obtained with a microCT (µCT). The CFD analysis shows similar tendencies and results with low relative difference compared to those of the experimental study, for high flow rates. For low flow rates the accuracy of this prediction reduces. The correlation between the computational and experimental results validates the robustness of the proposed methodology.
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Simulación por Computador , Líquido Extracelular/metabolismo , Ácido Láctico/química , Metilmetacrilatos/química , Modelos Biológicos , Polímeros/química , Andamios del Tejido/química , Permeabilidad , PoliésteresRESUMEN
Pyrimidine nucleotides are signaling molecules, which activate G protein-coupled membrane receptors of the P2Y family. P2Y(2) and P2Y(4) receptors are part of the P2Y family, which is composed of 8 subtypes that have been cloned and functionally defined. We have previously found that uridine-5'-triphosphate (UTP) reduces infarct size and improves cardiac function following myocardial infarct (MI). The aim of the present study was to determine the role of P2Y(2) receptor in cardiac protection following MI using knockout (KO) mice, in vivo and wild type (WT) for controls. In both experimental groups used (WT and P2Y(2)(-/-) receptor KO mice) there were 3 subgroups: sham, MI, and MI+UTP. 24h post MI we performed echocardiography and measured infarct size using triphenyl tetrazolium chloride (TTC) staining on all mice. Fractional shortening (FS) was higher in WT UTP-treated mice than the MI group (44.7±4.08% vs. 33.5±2.7% respectively, p<0.001). However, the FS of P2Y(2)(-/-) receptor KO mice were not affected by UTP treatment (34.7±5.3% vs. 35.9±2.9%). Similar results were obtained with TTC and hematoxylin and eosin stainings. Moreover, troponin T measurements demonstrated reduced myocardial damage in WT mice pretreated with UTP vs. untreated mice (8.8±4.6 vs. 12±3.1 p<0.05). In contrast, P2Y(2)(-/-) receptor KO mice pretreated with UTP did not demonstrate reduced myocardial damage. These results indicate that the P2Y(2) receptor mediates UTP cardioprotection, in vivo.
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Infarto del Miocardio/tratamiento farmacológico , Receptores Purinérgicos P2Y2/genética , Receptores Purinérgicos P2Y2/metabolismo , Uridina Trifosfato/uso terapéutico , Animales , Difosfatos/metabolismo , Genotipo , Inflamación/metabolismo , L-Lactato Deshidrogenasa/sangre , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infarto del Miocardio/metabolismo , Miocardio/citología , Miocardio/metabolismo , Troponina T/sangre , Remodelación Ventricular/efectos de los fármacosRESUMEN
Emergency Departments (ED) are a key element of the health system, and for various reasons must face the phenomenon of overcrowding, which requires that the Director of Hospitals and Emergency teams to implement various improvements in clinical and administrative management of these units, all aimed at improving the quality of care with the patients and their families on the center of actions. All this in a service where the diagnostic accuracy is complex and service times play an important role. In this chapter we review some elements of management both in terms of people, as relevant critical processes in a shared vision for professionals in the field of health and management processes...
Asunto(s)
Humanos , Masculino , Femenino , Servicios Médicos de Urgencia/métodos , Servicios Médicos de Urgencia/organización & administración , Servicios Médicos de Urgencia , Servicios Médicos de Urgencia/tendencias , Gestión en Salud , Administración Hospitalaria , Gestión de la Calidad TotalRESUMEN
BACKGROUND: Previous reports describe 30-40% of small intestine bacterial overgrowth (SIBO) in patients with chronic pancreatitis (CP), SIBO is a cause of persistent symptoms in this group of patients even when they are treated with pancreatic enzymes. AIM: To asses the frequency of SIBO in patients with CP. PATIENTS AND METHODS: We studied 14 patients with CP using an hydrogen breath test with lactulose to detect SIBO, a nonabsorbable carbohydrate, whose results are not influenced by the presence of exocrine insufficiency. Main symptoms and signs were bloating in 9 (64%), recurrent abdominal pain in 8 (57%), intermittent diarrhea in 5 (36%) and steatorrhea in 5 (36%). At the same time we studied a healthy control group paired by age and sex. RESULTS: SIBO was present in 13 of 14 patients with CP (92%) and in 1 of 14 controls (p<0.001). The only patient with CP and without SIBO was recently diagnosed and had minimal morphologic alterations in computed tomography and endoscopic pancreatography. CONCLUSIONS: SIBO is common in CP and may be responsible for persistent symptoms. Proper diagnosis and treatment could alleviate symptoms and improve quality of Ufe.