Síndrome de Brown bilateral adquirido / Bilateral acquired Brown syndrome

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Hoxa-10 and Cyclin D3 Overexpression in the Decidual Reaction in a Superovulation Protocol in Young Adult C57BL/6J Mice.

Following the performance of a superovulation protocol, multiple nodules were observed bilaterally in the uterine horns of 31 of 276 (11.2%) C57BL/6 J female mice aged 8.5 ± 0.6 (mean and standard error of mean) weeks. These lesions prevented embryo collection, and the uterine decidual reaction was suspected. Samples of pathological uteri (n = 20) and the normal genital tracts of donors treated with a similar superovulation protocol (control group, n = 10) were collected. Immunohistochemistry was performed to evaluate pancytokeratin, desmin, vimentin, progesterone receptor (PR), estrogen receptor α (ERα), Ki-67, cyclin D3 and c-Myc expression, as well as quantitative polymerase chain reaction to assess cyclin D3, Hoxa-10 and heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA expression. The uterine decidual reaction presented a high degree of structural organization and specifically affected the antimesometrial region of the endometrium. The abnormal decidual cells were large polygonal cells that were frequently polyploid or binucleated and strongly positive for desmin. Immunohistochemistry showed higher Ki-67 proliferation index and higher expression of PR and cyclin D3 in decidual cells in the antimesometrial aspect of the endometrium, compared to nondecidualized endometrial stromal cells in the mesometrial aspect of affected uteri, and compared to endometrial stromal cells in healthy uteri. High expression of cyclin D3 and Hoxa-10 mRNA was also observed in uteri affected by the decidual reaction. These results suggest that PR overexpression in endometrial stromal cells, likely due to high progesterone levels, triggers cyclin D3 and Hoxa-10 overexpression, which may be involved in the pathological mechanisms of the mouse uterine decidual reaction.

Nasopharyngeal bacterial burden and antibiotics: Influence on inflammatory markers and disease severity in infants with respiratory syncytial virus bronchiolitis.

OBJECTIVES: Animal studies suggest that RSV increases nasopharyngeal (NP) bacterial colonization facilitating bacterial infections. We investigated the influence of antibiotic treatment and colonization with potentially pathogenic bacteria on inflammatory markers and disease severity in RSV-infected in infants. METHODS: Healthy young infants hospitalized with RSV bronchiolitis (n = 136) and age-matched healthy controls (n = 23) were enrolled and NP samples cultured for potentially pathogenic bacteria including: Gram-positive bacteria (GPB): Staphylococcus aureus, Streptococcus pneumoniae, ß-hemolytic Streptococcus; and Gram-negative bacteria (GNB): Moraxella catarrhalis and Haemophilus influenzae. Clinical parameters and plasma IL-8, IL-6 and TNF-α concentrations were compared according to the bacterial class and antibiotic treatment. RESULTS: Antibiotic treatment decreased by 10-fold NP bacterial recovery. Eighty-one percent of RSV infants who did not receive antibiotics before sample collection were colonized with pathogenic bacteria. Overall, GNB were identified in 21% of patients versus 4% of controls who were mostly colonized with GPB. Additionally, in RSV patients NP white blood cell counts (p = 0.026), and blood neutrophils (p = 0.02) were higher in those colonized with potentially pathogenic bacteria versus respiratory flora. RSV patients colonized with GNB had higher plasma IL-8 (p = 0.01) and IL-6 (p < 0.01) concentrations than controls, and required longer duration of oxygen (p = 0.049). CONCLUSIONS: Infants with RSV bronchiolitis colonized with potentially pathogenic bacteria had increased numbers of mucosal and systemic inflammatory cells. Specifically, colonization with GNB was associated with higher concentrations of proinflammatory cytokines and a trend towards increased disease severity.

Whole blood gene expression profiles to assess pathogenesis and disease severity in infants with respiratory syncytial virus infection.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract infection (LRTI) and hospitalization in infants. Mostly because of the incomplete understanding of the disease pathogenesis, there is no licensed vaccine, and treatment remains symptomatic. We analyzed whole blood transcriptional profiles to characterize the global host immune response to acute RSV LRTI in infants, to characterize its specificity compared with influenza and human rhinovirus (HRV) LRTI, and to identify biomarkers that can objectively assess RSV disease severity. METHODS AND FINDINGS: This was a prospective observational study over six respiratory seasons including a cohort of infants hospitalized with RSV (n = 135), HRV (n = 30), and influenza (n = 16) LRTI, and healthy age- and sex-matched controls (n = 39). A specific RSV transcriptional profile was identified in whole blood (training cohort, n = 45 infants; Dallas, Texas, US) and validated in three different cohorts (test cohort, n = 46, Dallas, Texas, US; validation cohort A, n = 16, Turku, Finland; validation cohort B, n = 28, Columbus, Ohio, US) with high sensitivity (94% [95% CI 87%-98%]) and specificity (98% [95% CI 88%-99%]). It classified infants with RSV LRTI versus HRV or influenza LRTI with 95% accuracy. The immune dysregulation induced by RSV (overexpression of neutrophil, inflammation, and interferon genes, and suppression of T and B cell genes) persisted beyond the acute disease, and immune dysregulation was greatly impaired in younger infants (<6 mo). We identified a genomic score that significantly correlated with outcomes of care including a clinical disease severity score and, more importantly, length of hospitalization and duration of supplemental O2. CONCLUSIONS: Blood RNA profiles of infants with RSV LRTI allow specific diagnosis, better understanding of disease pathogenesis, and assessment of disease severity. This study opens new avenues for biomarker discovery and identification of potential therapeutic or preventive targets, and demonstrates that large microarray datasets can be translated into a biologically meaningful context and applied to the clinical setting. Please see later in the article for the Editors' Summary.

Análisis de los factores que influyen en la pérdida hemática en la nefrolitotomía percutánea: registro de la Asociación Española de Urología sobre la posición supina / Analysis of the Factors Affecting Blood Loss in Percutaneous Nephrolithotomy: A Registry of the Spanish Association of Urology in the Supine Position

Objetivo: La nefrolitotomía percutánea (NLP) es la técnica mínimamente invasiva de elección para el tratamiento de la litiasis renal mayor de 2 cm. El objetivo de este estudio es analizar los diferentes factores que influyen en el descenso de hemoglobina durante el procedimiento, realizado en posición supina. Material y métodos: Realizamos un estudio prospectivo multicéntrico observacional de la nefrolitotomía percutánea en posición supina, basado en el registro de la AEU. Se estudian los diferentes factores que influyen en el descenso de hemoglobina: datos demográficos y antropométricos, comorbilidad asociada, localización y tamaño de la litiasis, variantes anatómicas y aspectos técnicos del procedimiento. Resultados: Desde septiembre de 2008 hasta diciembre de 2012 se han registrado 397 NLP en posición supina, realizadas en 15 centros españoles. El descenso medio de hemoglobina fue 2,3 ± 1,5 g/dl y la tasa de transfusión de 5,5%. No hubo diferencias significativas en el descenso de hemoglobina entre varones y mujeres, IMC ni por grupos de edad. Tampoco existen diferencias entre los pacientes con antecedentes cardiovasculares, diabetes, HTA o tratamiento anticoagulante. El tamaño y la localización de la litiasis no influyen de forma significativa en la pérdida hemática. La duración del procedimiento (> o < 120 min), técnica de punción (ecografía, fluoroscopia), el tipo de dilatación del trayecto percutáneo (Alken, balón o Amplatz) y la ausencia de catéter de nefrostomía final (tubeless) no afectaron al descenso de hemoglobina. Únicamente el número de trayectos percutáneos (≥ 2) y el acceso a través de un cáliz medio tuvieron repercusión estadísticamente significativa en la pérdida hemática (p = 0,03 y p = 0,01 respectivamente) (AU)

Conclusiones: La NLP en posición supina es un procedimiento mínimamente invasivo para el tratamiento de litiasis renales múltiples y de gran tamaño (> 2 cm), que implica escasa pérdida hemática, con mínima tasa de transfusión de hemoderivados. Los únicos factores relacionados con mayor descenso de hemoglobina fueron el número de accesos percutáneos y la localización del trayecto en el cáliz medio (AU)

Objective: Percutaneous nephrolithotomy (PCNL) is the minimally invasive procedure of choice for removing renal stones larger than 2 cm. This study has aimed to identify the different variables that might influence decrease of hemoglobin during the surgery performed in supine position. Material and methods: A prospective, multicenter, observational study of supine PCNL, based on the Spanish Association of Urology database, was analyzed. The different preoperative and postoperative factors that might affect the decrease of hemoglobin were assessed: demographics and anthropometric data, comorbidities, size and location of the stones, anatomical variants and technical aspects of the procedure. Results: From September 2008 to December 2012, 397 supine PCNL procedures performed in 15 Spanish centers were registered. Mean hemoglobin decrease was 2.3 ± 1.5 g/dl and overall blood transfusion rate was 5.5%. No statistically significant differences were found between genders, body mass index (BMI) and age in terms of blood loss. There were also no differences between patients with cardiovascular, hypertensive, diabetic and anticoagulant treatment background. Blood loss was not significantly influenced by stone size and location. Technical aspects of the procedure as operative time (> 120 min ≤), access to the pelvi-caliceal system (ultrasound, fluoroscopy), percutaneous tract dilation technique (Alken, balloon or Amplatz) or placement of nephrostomy (tube versus tubeless) were not associated with differences in pre-op/post-op hemoglobin. Only multiple percutaneous tracts (≥ 2) and middle calix access were statistically significantly (P = 0.03 and P = 0.01) related with less blood loss (AU)

Conclusions: PCNL in supine position is a minimally invasive procedure for removal of large (≥ 2 cm) and multiple renal stones, with a low incidence of blood loss and minimal transfusion rate. Multiple percutaneous tracts and middle calix puncture were the only statistically significant variables associated with decrease in hemoglobin levels (AU)

Analysis of the factors affecting blood loss in percutaneous nephrolithotomy: a registry of the Spanish Association of Urology in the supine position.

OBJECTIVE: Percutaneous nephrolithotomy (PCNL) is the minimally invasive procedure of choice for removing renal stones larger than 2 cm. This study has aimed to identify the different variables that might influence decrease of hemoglobin during the surgery performed in supine position. MATERIAL AND METHODS: A prospective, multicenter, observational study of supine PCNL, based on the Spanish Association of Urology database, was analyzed. The different preoperative and postoperative factors that might affect the decrease of hemoglobin were assessed: demographics and anthropometric data, comorbidities, size and location of the stones, anatomical variants and technical aspects of the procedure. RESULTS: From September 2008 to December 2012, 397 supine PCNL procedures performed in 15 Spanish centers were registered. Mean hemoglobin decrease was 2.3±1.5 g/dl and overall blood transfusion rate was 5.5%. No statistically significant differences were found between genders, body mass index (BMI) and age in terms of blood loss. There were also no differences between patients with cardiovascular, hypertensive, diabetic and anticoagulant treatment background. Blood loss was not significantly influenced by stone size and location. Technical aspects of the procedure as operative time (> 120 min ≤), access to the pelvi-caliceal system (ultrasound, fluoroscopy), percutaneous tract dilation technique (Alken, balloon or Amplatz) or placement of nephrostomy (tube versus tubeless) were not associated with differences in pre-op/post-op hemoglobin. Only multiple percutaneous tracts (≥2) and middle calix access were statistically significantly (P=.03 and P=.01) related with less blood loss. CONCLUSIONS: PCNL in supine position is a minimally invasive procedure for removal of large (≥2 cm) and multiple renal stones, with a low incidence of blood loss and minimal transfusion rate. Multiple percutaneous tracts and middle calix puncture were the only statistically significant variables associated with decrease in hemoglobin levels.

Tratamiento del cáncer de próstata y cáncer renal con fármacos orales (abiraterona y antiangiogénicos): posicionamiento de la Asociación Española de Urología / Treatment of prostate and renal cancer with oral drugs (abiratarone and antiangiogenic agents): Positioning statement from the Spanish Association of Urology

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Innate immune dysfunction is associated with enhanced disease severity in infants with severe respiratory syncytial virus bronchiolitis.

BACKGROUND: Most patients with respiratory syncytial virus (RSV) bronchiolitis requiring admission to the pediatric intensive care unit (PICU) have no risk factors for severe disease. We sought to investigate the relationship between serum cytokine concentrations, innate immune responsiveness, and RSV disease severity. METHODS: Previously healthy infants (median age, 2.6 months) with RSV bronchiolitis (PICU, n = 20; floor, n = 46) and healthy matched controls (n = 14) were enrolled, and blood samples were obtained within 24 hours of admission to measure plasma tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) concentrations and, whole blood lipopolysaccharide-stimulated cytokine production capacity. RESULTS: Plasma IL-6, IL-8, and IL-10 concentrations were comparable between PICU and floor patients, but higher than in healthy controls (P < .05). In contrast, TNF-α, IL-6, and IL-8 production capacity was significantly decreased in PICU compared with both floor patients and healthy controls. In adjusted analyses, only impaired TNF-α and IL-8 production capacity were associated with longer length of stay (P = .035) and greater disease severity scores (P = .001). CONCLUSIONS: Infants with severe RSV bronchiolitis had increased plasma cytokine concentrations and yet impaired innate immunity cytokine production capacity, which predicted worse disease outcomes. Immune monitoring of otherwise healthy infants with RSV lower respiratory tract infection could help identify patients at risk for severe disease at the time of hospitalization.

Mixed epithelial and stromal tumour of the kidney with luteinised ovarian stroma.

We report a case of a 9-cm mixed epithelial and stromal tumour of the kidney in an obese 70-year-old woman with diabetes. The ovarian-type stroma had a spindle cell component that was positive for progesterone receptors and had the hitherto unreported presence of abundant foci of luteinised stromal cells with characteristic immunohistochemical positivity to alpha-inhibin, calretinin, aromatase and gonadotropin-releasing hormone (GnRH) receptors. We conclude that the stromal component is identical to ovarian cortical stroma. We believe that ovarian-type stroma occurs in extragenital tumours as a result of an epithelial-stromal interaction in an environment of hormonal hyperstimulation.

[Atypical presentation of ocular hypertension following myopic LASIK]. / Presentación atípica de la hipertensión ocular en los pacientes intervenidos de LASIK miópico.

OBJECTIVE: We present a masquerade syndrome recently described following uneventful laser in situ keratomileusis (LASIK). If misdiagnosed or left unattended, this condition can lead to severe visual loss. METHODS: Findings concerning ten patients who underwent uneventful myopic LASIK, but who presented with a granular haze in the interface in the early postoperative period, are described. Initially, some of the patients were treated for diffuse lamellar keratitis with an intensive course of topical steroids, but, rather than improving, the haziness of the interface worsened or remained the same, and was even accompanied by the development of epithelial edema. RESULTS: Tonometry led to the diagnosis of ocular hypertension induced by the steroid therapy. The clinical picture resolved completely with topical hypotensive treatment and with the cessation of steroid treatment. CONCLUSION: In the early postoperative period following LASIK an atypical presentation of ocular hypertension can occasionally be observed. A high index of suspicion of this diagnosis must be maintained due to the inaccuracy of tonometry after LASIK and the similarity of this clinical picture with diffuse lamellar keratitis. These cases emphasize the importance of taking into account underestimation of the intraocular pressure after myopic LASIK.

Presentación atípica de la hipertensión ocular en los pacientes intervenidos de Lasik miópico / Atypical presentation of ocular hypertension following myopic Lasik

Objetivo: Se presenta un síndrome mascarada descrito recientemente en los pacientes sometidos a queratomileusis in situ asistida por láser excimer (LASIK). Si no se diagnostica a tiempo o si no recibe el correcto tratamiento, puede conducir a una pérdida visual severa.Métodos: Se exponen los casos clínicos de diez pacientes intervenidos de LASIK miópico sin incidencias, y que en el postoperatorio precoz presentaron un haze granular en la interfase corneal de ambos ojos. Algunos inicialmente fueron tratados como queratitis lamelares difusas con corticoides tópicos intensivos. La turbidez de la interfase en lugar de mejorar, se mantuvo o empeoró, desarrollando incluso edema epitelial.Resultados: La tonometría condujo al diagnóstico de hipertensión ocular inducida por los esteroides. La clínica se resolvió completamente con tratamiento médico hipotensor tópico y suprimiendo los corticoides.Conclusión: Esta presentación atípica de una hipertensión ocular puede producirse tras un LASIK reciente. La inexactitud en las técnicas tonométricas tras esta cirugía y la similitud del cuadro con la queratitis lamelar difusa deben hacernos mantener un alto índice de sospecha clínica. Estos casos enfatizan la importancia de la subestimación de la PIO tras el LASIK miópico

Objective: We present a masquerade syndrome recently described following uneventful laser in situ keratomileusis (LASIK). If misdiagnosed or left unattended, this condition can lead to severe visual loss.Methods: Findings concerning ten patients who underwent uneventful myopic LASIK, but who presented with a granular haze in the interface in the early postoperative period, are described. Initially, some of the patients were treated for diffuse lamellar keratitis with an intensive course of topical steroids, but, rather than improving, the haziness of the interface worsened or remained the same, and was even accompanied by the development of epithelial edema.Results: Tonometry led to the diagnosis of ocular hypertension induced by the steroid therapy. The clinical picture resolved completely with topical hypotensive treatment and with the cessation of steroid treatment.Conclusion: In the early postoperative period following LASIK an atypical presentation of ocular hypertension can occasionally be observed. A high index of suspicion of this diagnosis must be maintained due to the inaccuracy of tonometry after LASIK and the similarity of this clinical picture with diffuse lamellar keratitis. These cases emphasize the importance of taking into account underestimation of the intraocular pressure after myopic LASIK

A modified rhTGF-beta1 and rhBMP-2 are effective in initiating a chondro-osseous differentiation pathway in bone marrow cells cultured in vitro.

Rat bone marrow cells were cultured in vitro in a collagen-gel medium at 0.5% fetal bovine serum concentration for 10 days in the presence of recombinant human transforming growth factor-beta-1, genetically engineered to contain a collagen binding domain (rhTGF-beta1-F2), or a commercial rhTGF-beta1. To compare the effects of TGF-betas with other growth factors in which the osteogenic capacity has been widely documented, a recombinant human bone morphogenetic protein (rhBMP-2) was evaluated. Once serum conditions compatible with growth were re-established, the selected cells were cultured for 6 more days in the presence of the growth factor. In the last 2 days, dexamethasone (dex) and beta-glycerophosphate (beta-GP) were added to promote osteogenesis. After this 16-day period, cells were placed into diffusion chambers or demineralized bone matrix (DBM) implants, and implanted subdermally on the backs of rats for 28 days. Biochemical, histological, and immunohistochemistry analysis provided evidence of cartilage (commercial rhTGF-beta1-treated cells), osteoid (rhTGF-beta1-F2-treated cells), and bone tissues (rhBMP-2 treated cells), inside the diffusion chambers, whereas bone, cartilage, and osteoid were observed inside the DBM implants under any of the three growth factors effect. Our study advances the technology capable of selecting a cell population from bone marrow that, in the presence of rhTGF-beta1 or rhBMP-2 in vitro, achieves chondro-osteogenic potential in vitro and in vivo.

Células madre e ingeniería tisular ósea. Bases celulares y perspectivas terapéuticas / Stem cells and bone tissue engineering

Los avances en el conocimiento de las proteínas morfogenéticas de hueso (BMP) han propiciado su utilización directa en las reparaciones óseas, planteando la falta de control sobre el tiempo que estas proteínas permanecen en la lesión, la actividad real de las mismas y la imprescindible necesidad de células osteogénicas en el lugar de aplicación, efectores últimos de la acción inductora. Por lo tanto, cuando la falta de células sea el problema fundamental, la aplicación directa de factores osteoinductores, aun cuando en otras circunstancias puedan ser más útiles, no producirá los resultados esperados, siendo el aporte de células osteoprogenitoras la línea de actuación más apropiada, bien directamente o a través de un material transportador osteoconductor, sin descartar la posibilidad de inyección sistémica. Entre las aplicaciones directas a la cirugía ortopédica de esta ingeniería tisular, está la consecución de artrodesis del raquis como tratamiento de inestabilidades de origen diverso. Los problemas actuales se centran en el fracaso de la fusión y en la morbilidad de la zona donante de autoinjerto. En las artroplastias la ingeniería tisular muestra también un campo de aplicación inmediato, si bien antes es necesario solucionar los problemas relativos a la estabilidad primaria. En cualquier caso, la validez de las conclusiones de la ingeniería tisular pasará por su verificación en modelos clínicos humanos con diseños epidemiológicos prospectivos metodológicamente correctos. Los problemas éticos y legales serán, en fin, los condicionantes fundamentales para la generalización de la ingeniería tisular como propuesta terapéutica. En este trabajo se realiza una revisión conceptual de estos problemas (AU)

Síndrome de WEBINO como presentación de miastenia gravis / The WEBINO syndrome as putset of myasthenia gravis

Caso clínico: Presentamos el caso de un varón de 37 años que acudió a urgencias por diplopía de aparición brusca. A la exploración, observamos una exotropía severa, un déficit de convergencia y los signos típicos de una oftalmoplejía internuclear (OIN) bilateral: ausencia de aducción en ambos ojos y abducción nistágmica de ambos ojos. En conjunto, los signos clínicos que presentaba este paciente constituyen el síndrome de WEBINO (wall eyed internuclear ophthalmoplegia).Discusión: Tras descartar las causas más frecuentes de OIN bilateral (Esclerosis múltiple, trastorno vascular, etc.) llegamos al diagnóstico de Miastenia Gravis mediante el test de Tensilon y la electromiografía. El tratamiento con piridostigmina produjo en dos meses una remisión completa del cuadro. Esta es la primera vez que se describe un síndrome de WEBINO producido por miastenia gravis en la literatura. (AU)

[The usefulness of abdominal echography in the diagnosis of portal hypertension in cirrhotic patients]. / Utilidad de la ecografía abdominal en el diagnóstico de hipertensión portal en pacientes cirróticos.

The differences in sonographic measurements of the splanchnic vessels, their modifications during respiration, the spleen size and the presence of collaterals of the portal system among 110 cirrhotic patients with portal hypertension and 30 control subjects are analyzed to verify the usefulness of conventional sonography in the diagnosis of portal hypertension. We achieved a sensitivity above 70% and a specificity of at least 90% with the following signs: 1) dilation of portal, splenic and superior mesenteric veins, 2) limited variations of the latter two during respiration, and 3) splenomegaly. A higher sensitivity was achieved considering variations in splenic caliber during respiration under 33% (91%) or superior mesenteric vein during forced expiration above or equal than 7 mm (88%). These measurements could be found in 71.8% and 57.2% respectively. On the other hand, values of portal vein and spleen size were easily obtained. The usefulness of all measurements persists if we take into account only patients with Child-Pugh score < 7. Collateral circulation was demonstrated in 18%. Portal vein above 14 mm, variations in splenic caliber under 13% or superior mesenteric vein during forced expiration above or equal than 9 mm were obtained in any of control subjects but respectively in 33%, 46% and 69% of patients in portal hypertension group. We conclude that ultrasonography is a reliable and noninvasive tool in the diagnosis of portal hypertension in cirrhotic patients.

[Esophageal carcinoma after the endoscopic sclerotherapy of varices]. / Carcinoma esofágico tras escleroterapia endoscópica de varices.

We report the case of a 52-years-old smoking male, diagnosed of liver cirrhosis, who developed a squamous cell carcinoma of the esophagus 36 months after undergoing endoscopic injection sclerotherapy for bleeding esophageal varices. Nine courses with 3% polidocanol were performed along 10 months. It was injected intra and paravariceal at a total dose of 117 ml. The relationship between endoscopic injection sclerotherapy and developing squamous cell carcinoma of the esophagus is discussed.