Rinosinusitis micótica alérgica con destrucción de base de cráneo / Allergic fungal rhinosinusitis with skull base destruction

La sinusitis micótica alérgica es una enfermedad inflamatoria de la mucosa rinosinusal producida por hongos que pueden aislarse de la cavidad de nasal de individuos sanos. Se produce indirectamente por los hongos que actúan como antígeno y desencadenan una reacción inmunológica mediada por IgE que origina pólipos y una secreción mucosa espesa con detritus e hifas denominada mucina. Su presentación clínica más frecuente es una sinusitis crónica unilateral o bilateral con pólipos. Con menos frecuencia, las sustancias originadas por la desgranulación de los eosinófilos producen remodelación o destrucción ósea y la sinusitis puede simular una neoplasia. Se describe el caso clínico de un paciente que padeció una sinusitis micótica alérgica con destrucción ósea masiva de la base del cráneo y que tuvo extensión intracraneal extradural e intraorbitaria de la enfermedad. Fue tratado con éxito mediante cirugía y corticoides. (AU)

Allergic fungal sinusitis is an inflammatory disease of the rhinosinusal mucosa caused by fungi that can be isolated from the nasal cavity of healthy individuals. The pathology is produced indirectly by the fungus that acts as an antigen and triggers an IgE-mediated allergic reaction that causes polyps and a thick mucous discharge with detritus and hyphae called mucin. Its most common clinical presentation is unilateral or bilateral chronic sinusitis with polyps. Less commonly, substances originated by the degranulation of eosinophils cause bone remodeling or destruction, and sinusitis can simulate a neoplasia. We describe the clinical case of a patient who suffered from allergic fungal sinusitis with massive bone destruction of the skull base and who had intracranial, extradural and intraorbital extension of the disease. He was successfully treated with surgery and corticosteroids.Key words: allergic fungal sinusitis, intracranial extension, endoscopic surgery, transorbital transpalpebral approach. (AU)

Cauterización transoral de la arteria maxilar interna en la fosa infratemporal: informe de un caso / Transoral cauterization of the internal maxillary artery in the infratemporal fossa: case report

Se describe el caso clínico de una paciente de 84 años que tuvo epistaxis recidivante por padecer enfermedad de Rendu-Osler-Weber. Tuvo antecedentes de diversos tratamientos quirúrgicos que incluyeron el cierre de la fosa nasal izquierda (operación de Young). Por la persistencia de epistaxis izquierda se indicó una angiografía y embolización. Esta última no se hizo porque se diagnosticaron anastomosis entre el sistema carotídeo externo y el interno. Se realizó un abordaje intraoral paramaxilar asistido con endoscopios para cauterizar la arteria maxilar interna en la fosa infratemporal y un abordaje externo para cauterizar la arteria etmoidal anterior solucionando la epistaxis. (AU)

The clinical case of an 84-year-old patient who had recurrent epistaxis due to Rendu-Osler- Weber disease is described. She had a history of various surgical treatments including closure of the left nostril (Young's operation).Due to the persistence of left epistaxis, angiography and embolization were indicated. The latter was not done because anastomosis between the external and internal carotid system was diagnosed. An intraoral paramaxillary approach assisted with endoscopes was performed to cauterize the internal maxillary artery in the infratemporal fossa and an external approach to cauterize the anterior ethmoidal artery solving the epistaxis. (AU)

The use of urinary osmolality to evaluate postoperative renal function in children with ureteropelvic junction obstruction.

INTRODUCTION: Split renal function measured in a diuretic renogram is the most popular tool in initial assessment and follow-up of patients with ureteropelvic junction obstruction (UPJO). This study aims to evaluate the use of maximum urinary osmolality after desmopressin administration (DDAVP) to detect renal dysfunction. PATIENTS AND METHODS: 56 children (33 males, 23 females) diagnosed with UPJO underwent quantification of the maximum urinary osmolality (UOsm) at diagnosis. 41 of these children (28 males, 13 females) underwent surgery for UPJO and quantification of the UOsm before and after the surgical intervention (six to 18 months postoperatively) and were included in this longitudinal study. RESULTS AND DISCUSSION: At diagnosis, UOsm measured after desmopressin administration was abnormal in 64% of patients. After surgical intervention, this rate decreased to 53%. At initial assessment, high creatinine levels were found in 32% of infants younger than one year of age. Albumin/Cr and NAG/Cr ratios were elevated in 12% and 7% of cases, respectively. After surgical intervention, an improvement in the NAG/creatinine ratio and creatinine levels was observed. Preoperative split renal function of the affected kidney was less than 45% in 39% of cases, normal in 44%, and greater than 55% in 17%; in these three subgroups, no differences in renal function markers were found. CONCLUSIONS: The most sensitive parameter to detect alterations in renal function in children with UPJO is the UOsm and, therefore, the most useful in the follow-up after surgery. No correlation was found between other functional and morphological parameters obtained on renal ultrasound and renogram.

Validation of a novel online depression symptom severity rating scale: the R8 Depression.

BACKGROUND: An automated web-based assessment and monitoring system ( www.psynary.com ) has been developed to assist non-specialist clinicians in managing common mood and anxiety disorders. Psynary promotes the use of standardised outcome measures to assess symptom severity and optimise treatments with the aim of improving outcomes and enabling faster recovery. This paper analyses the results from two parallel studies in New Zealand and Japan (OptiMA-1 NZ and Japan) to assess the validity of the R8 Depression scale, one of the system's core outcome measures. METHODS: Clinical samples were recruited from a public secondary care and a private psychiatry clinic. Participants completed the outcome measures for the study via the online Psynary system. The R8 Depression scale is a 30-item questionnaire which includes all symptom domains covered in the ICD-10 classification of depression. The Patient Health Questionnaire (PHQ-9) was completed at the same time points as the R8 Depression, with a smaller sample also completing a paper-based Quick Inventory of Depressive Symptomatology (QIDS-SR16). Internal validity was quantified via Cronbach's alpha and Guttman lower bounds method. External validation against the PHQ-9 and QIDS used the Pearson's and Kendall's correlation coefficients. Severity categories were set using a multivariate regression model. RESULTS: 270 patients participated in the study and completed a maximum of 1 baseline and 5 reviews within a 90-day period, giving a total of 1124 assessments with the PHQ-9 also being completed in 1053 of these assessments. R8 Depression normative data was also collected from 204 non-clinical volunteers with 187 of these also completing the PHQ9. Internal reliability scores were all higher than 0.9 (n = 1328). There was overall good external validity when comparing the R8 Depression to the PHQ-9, with a correlation of 0.91 for the combined normative and clinical samples (n = 1240). CONCLUSIONS: The R8 Depression has been developed as a patient-rated outcome measure for depression for administration on an online system called "Psynary". It has high internal and external validity against current widely used scales. Further work is underway to determine the sensitivity to change of the R8 Depression.

Esophageal deviation with vacuum suction and mechanical deflection during ablation of atrial fibrillation: First in man evaluation.

Deviation of the esophagus during atrial fibrillation (AF) ablation can reduce esophageal injury. This study reports upon a novel esophageal retractor that utilizes vacuum suction and mechanical deflection to deviate the esophagus. The device was used in seven patients undergoing cryoballoon AF ablation. The esophagus was deviated 31.9 ± 4.4 mm to the right and 28.2 ± 5.9 mm to the left. Endoscopy at 4.4 ± 1.5 days postablation showed no esophageal injury. This study demonstrates the safe and effective deviation of the esophagus without a trailing edge with an esophageal retractor utilizing vacuum suction and mechanical deflection.

Acné queloideo de la nuca: excelente respuesta al tratamiento con imiquimod 5% / Keloid acne of the nape: excellent response to treatment with imiquimod 5%

El acné queloideo de la nuca (AKN) o foliculitis esclerosante es un proceso inflamatorio crónico del folículo piloso en la región de la nuca. Su incidencia es baja y su etiología desconocida. Afecta con mayor frecuencia a hombres de mediana edad y de raza negra. A lo largo del tiempo se han utilizado diferentes modalidades terapéuticas con resultados variables. Presentamos el caso de un paciente con AKN que mostró una excelente respuesta al uso diario de imiquimod 5% tópico durante ocho semanas

Keloid acne of the neck (AKN) or sclerosing folliculitis of the nape of the neck is a chronic inflammatory process of the nape region. Its incidence is low and its etiology is unknown. It mainly affects brown-black males in middle age. Different treatment modalities have been used with different responses. We present the case of a patient with AKN who presented an excellent response to the daily use of topical imiquimod 5% for eight weeks

Cirugía transoral en hemangiomas de laringe e hipofaringe en adultos / Transoral surgery in laryngeal hemangiomas e hypopharynx in adults

Los hemangiomas son tumores benignos infrecuentes en la laringe. El tratamiento está indicado cuando el tumor produce síntomas (disnea, hemoptisis, odinofagia) y también cuando el riesgo de hemorragia severa por traumatismo es alto. Tres hemangiomas de laringe e hipofaringe fueron tratados con éxito por vía transoral con láser de C02 y radiofrecuencia. Todos los pacientes se alimentaron por vía oral a las 24/48 horas y ninguno tuvo traqueostomía. La tasa de resección completa de los hemangiomas tratados por vía transoral fue 100%. (AU)

Hemangiomas are a rare type of benign tumors of the larynx. The treatment is indicated when the tumor produces symptoms (dyspnea, hemoptysis, odynophagia) and also when the risk of severe bleeding from trauma is high. Three hemangiomas of the larynx and hypopharynx were successfully treated transorally with C02 laser and radiofrequency. All were orally fed at 24/48 hours, and none had a tracheostomy The complete resection rate of hemangiomas treated transorally was 100%. (AU)

Tratamiento endovascular para epistaxis posterior / Endovascular treatment for posterior epistaxis / Tratamento endovascular para epistaxe posterior

INTRODUCCIÓN: Las complicaciones del tratamiento endovascular son infrecuentes. Las lesiones isquémicas a los tejidos de la cabeza y el cuello se han reportado de forma esporádica, siendo complicaciones raras gracias al aporte redundante de la amplia red anastomótica en esta región. OBJETIVOS: Realizar una análisis estadístico de los pacientes que se sometieron a tratamiento endovascular por epistaxis, identificando las complicaciones, y realizar una revisión comparada con la literatura disponible evaluando la efectividad del tratamiento...

INTRODUCTION: Complications of endovascular treatment are infrequent. Ischemic injuries to the tissues of the head and neck have been reported sporadically, being rare complications thanks to the redundant contribution of the extensive anastomotic network in this region. OBJECTIVES: Perform a statistical analysis of patients who underwent endovascular treatment for epistaxis, identifying complications and conducting a review compared to the available literature evaluating the effectiveness of the treatment...

INTRODUÇÃO: Complicações do tratamento endovascular são infrequentes. Lesões isquêmicas nos tecidos da cabeça e pescoço têm sido relatadas esporadicamente, sendo complicações raras graças à contribuição redundante da extensa rede anastomótica nessa região. OBJETIVOS: Realizar uma análise estatística dos pacientes que foram submetidos a tratamento endovascular para epistaxe, identificando complicações e realizando uma revisão em comparação com a literatura disponível que avalia a eficácia do tratamento...

Tratamiento quirúrgico de la epistaxis en la enfermedad de Rendu Osler Weber / Epistaxis surgical treatment in Rendu Osler Weber disease / Tratamento cirúrgico da epistaxe na doença de Rendu Osler Weber

Introducción: la telangiectasia hemorrágica hereditaria (THH) o Rendu Osler Weber es una enfermedad genética que produce falta de soporte elástico en el endotelio vascular, lo cual genera sangrado ante el mínimo trauma producido. Aunque la morbilidad y mortalidad en esta patología resultan de las malformaciones vasculares presentes en pulmón, hígado y cerebro, la calidad de vida se altera significativamente debido a los episodios recurrentes de epistaxis. Objetivos: El objetivo del presente trabajo es determinar el porcentaje de pacientes con diagnóstico de THH que requirieron uno o más tratamientos quirúrgicos para el sangrado nasal y realizar una revisión bibliográfica de las técnicas quirúrgicas utilizadas...

Introduction: HHT is a genetic disease that causes lack of elastic support in the vascular endothelium, which causes bleeding at the slightest trauma occurred. The quality of life is significantly altered due to recurrent episodes of epistaxis. The aim of this study is to determine the percentage of patients diagnosed with HHT, requiring one or more surgical procedures for treatment of epistaxis, and perform a literature review of surgical techniques used. Methods: The medical records of patients with Osler Rendu disease requiring surgical treatment for epistaxis, who consulted the service of Otolaryngology of the Hospital Italiano de Buenos Aires were analyzed...

Introdução: o THH é uma doença genética que provoca falta de suporte elástico no endotélio vascular, que provoca o sangramento ao menor trauma ocorreu. A qualidade de vida é significativamente alterada devido a episódios recorrentes de epistaxe. O objetivo deste estudo é determinar a porcentagem de pacientes diagnosticados com HHT, exigindo um ou mais procedimentos cirúrgicos para o tratamento de epistaxe, e realizar uma revisão da literatura sobre técnicas cirúrgicas utilizadas...

Anti-Tumor Effects of Peptide Therapeutic and Peptide Vaccine Antibody Co-targeting HER-1 and HER-2 in Esophageal Cancer (EC) and HER-1 and IGF-1R in Triple-Negative Breast Cancer (TNBC).

Despite the promise of targeted therapies, there remains an urgent need for effective treatment for esophageal cancer (EC) and triple-negative breast cancer (TNBC). Current FDA-approved drugs have significant problems of toxicity, safety, selectivity, efficacy and development of resistance. In this manuscript, we demonstrate that rationally designed peptide vaccines/mimics are a viable therapeutic strategy for blocking aberrant molecular signaling pathways with high affinity, specificity, potency and safety. Specifically, we postulate that novel combination treatments targeting members of the EGFR family and IGF-1R will yield significant anti-tumor effects in in vitro models of EC and TNBC possibly overcoming mechanisms of resistance. We show that the combination of HER-1 and HER-2 or HER-1 and IGF-1R peptide mimics/vaccine antibodies exhibited enhanced antitumor properties with significant inhibition of tumorigenesis in OE19 EC and MDA-MB-231 TNBC cell lines. Our work elucidates the mechanisms of HER-1/IGF-1R and HER-1/HER-2 signaling in these cancer cell lines, and the promising results support the rationale for dual targeting with HER-1 and HER-2 or IGF-1R as an improved treatment regimen for advanced therapy tailored to difference types of cancer.

Crystal structures of the carboxyl cGMP binding domain of the Plasmodium falciparum cGMP-dependent protein kinase reveal a novel capping triad crucial for merozoite egress.

The Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) is a key regulator across the malaria parasite life cycle. Little is known about PfPKG's activation mechanism. Here we report that the carboxyl cyclic nucleotide binding domain functions as a "gatekeeper" for activation by providing the highest cGMP affinity and selectivity. To understand the mechanism, we have solved its crystal structures with and without cGMP at 2.0 and 1.9 Å, respectively. These structures revealed a PfPKG-specific capping triad that forms upon cGMP binding, and disrupting the triad reduces kinase activity by 90%. Furthermore, mutating these residues in the parasite prevents blood stage merozoite egress, confirming the essential nature of the triad in the parasite. We propose a mechanism of activation where cGMP binding allosterically triggers the conformational change at the αC-helix, which bridges the regulatory and catalytic domains, causing the capping triad to form and stabilize the active conformation.

Insulin-like growth factor-1 receptor signaling increases the invasive potential of human epidermal growth factor receptor 2-overexpressing breast cancer cells via Src-focal adhesion kinase and forkhead box protein M1.

Resistance to the human epidermal growth factor receptor (HER2)-targeted antibody trastuzumab is a major clinical concern in the treatment of HER2-positive metastatic breast cancer. Increased expression or signaling from the insulin-like growth factor-1 receptor (IGF-1R) has been reported to be associated with trastuzumab resistance. However, the specific molecular and biologic mechanisms through which IGF-1R promotes resistance or disease progression remain poorly defined. In this study, we found that the major biologic effect promoted by IGF-1R was invasion, which was mediated by both Src-focal adhesion kinase (FAK) signaling and Forkhead box protein M1 (FoxM1). Cotargeting IGF-1R and HER2 using either IGF-1R antibodies or IGF-1R short hairpin RNA in combination with trastuzumab resulted in significant but modest growth inhibition. Reduced invasion was the most significant biologic effect achieved by cotargeting IGF-1R and HER2 in trastuzumab-resistant cells. Constitutively active Src blocked the anti-invasive effect of IGF-1R/HER2 cotargeted therapy. Furthermore, knockdown of FoxM1 blocked IGF-1-mediated invasion, and dual targeting of IGF-1R and HER2 reduced expression of FoxM1. Re-expression of FoxM1 restored the invasive potential of IGF-1R knockdown cells treated with trastuzumab. Overall, our results strongly indicate that therapeutic combinations that cotarget IGF-1R and HER2 may reduce the invasive potential of cancer cells that are resistant to trastuzumab through mechanisms that depend in part on Src and FoxM1.

Determinación de la cicloxigenasa-2en carcinoma escamocelular de lengua bien diferenciado, moderadamente diferenciado y poco diferenciado / Determination of cyclooxigenase-2 in well-differentiated, moderately differ entiated and P oorly differ entiated squamous cell carcinoma of the tongue

Propósito: Determinar y comparar la expresión de la cicloxigenasa-2 (COX-2) en el carcinomaescamocelular de lengua (CECL) según el grado de diferenciación, con la finalidadde explorar si este puede ser un marcador molecular útil en el diagnóstico y pronóstico delcáncer de la cavidad oral. Métodos: Se utilizaron 45 especímenes con CECL, 15 de ellos biendiferenciados, 12 moderadamente diferenciados, 18 mal diferenciados, un control positivode carcinoma de colon y un control negativo de mucosa oral sana. La identificación de laCOX-2 se obtuvo por medio de inmunohistoquímica. Resultados: La muestra de mucosalingual sana expresó la COX-2 en bajo nivel; el 60 % de las quince muestras de carcinomaescamocelular diferenciado mostraron un bajo nivel de expresión, el 41,3 % de 12 muestrasde carcinoma moderadamente diferenciado mostraron una alta expresión, y el 74 % de 18muestras de carcinoma no diferenciado mostraron una alta expresión de la enzima. Conclusión:La expresión de la COX-2 aumenta si el carcinoma es indiferenciado, lo cual sugiereque esta enzima podría desempeñar un papel importante en el desarrollo histopatológicodel CECL, tanto en las etapas iniciales como en las tardías...

Aim: Determine and compare the expression of cyclooxygenase-2 (COX-2) in squamouscell carcinoma of the tongue (SCCT) in three degrees of differentiation, in order to verify ifthis may be a molecular marker useful in the diagnosis and prognosis of oral cavity cancer.Methods: The sample consisted of 45 specimens with SCCT (15 well-differentiated, 12 moderatelydifferentiated, 18 poorly differentiated), a positive control (colon carcinoma) and anegative control (healthy oral mucosa). The identification of COX-2 was obtained throughimmunohistochemistry. Results: Samples of healthy lingual mucosa showed a low expressionof COX-2, 60 % of the 15 samples of well-differentiated squamous cell carcinoma showeda low expression of COX-2, 41.3 % of 12 samples of moderately differentiated carcinomashowed high expression, and 74 % of the 18 non-differentiated carcinoma samples showeda high expression of the enzyme. Conclusion: The expression of COX-2 increases in lessdifferentiated squamous cell carcinoma, which suggests that identification of COX-2 in thehistologic development of squamous carcinoma of the tongue might be important in thedifferentiation of both, the early and late stag es...

Anatomic hepatectomy as a definitive treatment for hepatolithiasis: a cohort study.

BACKGROUND: Treatment requirements in hepatolithiasis may vary and may involve a multidisciplinary approach. Surgical resection has been proposed as a definitive treatment. OBJECTIVES: This study aimed to evaluate the clinical results of anatomic liver resection among Chilean patients with hepatolithiasis. METHODS: An historical cohort study was conducted. Patients who underwent hepatectomy as a definitive treatment for hepatolithiasis from January 1990 to December 2010 were included. Patients with a preoperative diagnosis of cholangiocarcinoma were excluded. Preoperative, operative and postoperative variables were evaluated. RESULTS: A total of 52 patients underwent hepatectomy for hepatolithiasis. The mean ± standard deviation patient age was 49.8 ± 11.8 years (range: 24-78 years); 65.4% of study subjects were female. A total of 75.0% of subjects had a history of previous cholecystectomy. The main presenting symptom was abdominal pain (82.7%). Hepatic involvement was noted in the left lobe in 57.7%, the right lobe in 34.6% and bilaterally in 7.7% of subjects. The rate of postoperative clearance of the biliary tree was 90.4%. Postoperative morbidity was 30.8% and there were no postoperative deaths. Three patients had recurrence of hepatolithiasis, which was associated with Caroli's disease in two of them. Overall 5-year survival was 94.5%. CONCLUSIONS: Anatomic liver resection is an effective treatment in selected patients with hepatolithiasis and is associated with low morbidity and no mortality. At longterm follow-up, anatomic hepatectomy in these patients was associated with a lower rate of recurrence.

Development of an amine dehydrogenase for synthesis of chiral amines.

A leucine dehydrogenase has been successfully altered through several rounds of protein engineering to an enantioselective amine dehydrogenase. Instead of the wild-type α-keto acid, the new amine dehydrogenase now accepts the analogous ketone, methyl isobutyl ketone (MIBK), which corresponds to exchange of the carboxy group by a methyl group to produce chiral (R)-1,3-dimethylbutylamine.

Development of a thermostable glucose dehydrogenase by a structure-guided consensus concept.

Instability under non-native processing conditions, especially at elevated temperatures, is a major factor preventing the widespread adoption of biocatalysts for industrial synthesis. A crucial distinction of many redox enzymes used to synthesize chiral compounds is the need for cofactors (e.g., NAD(P)(H)) for function. Because of the prohibitively high prices of nicotinamide cofactors, a robust cofactor-regenerating enzyme is required for the economical synthesis of fine chemicals by biocatalysis. Here we test the structure-guided consensus for the generation of a thermostable glucose dehydrogenase (GDH). The consensus sequence in combination with additional knowledge-based criteria was used to select amino acids for substitutions. Using this approach we generated 24 variants, 11 of which showed higher thermal stability than the wild-type GDH, a success rate of 46 %. Of the 24 variants, seven were located at the subunit interface-known to influence GDH stability-and six were more stable (86 % success). The best variants feature a half-life of approximately 3.5 days at 65 degrees C, in contrast to approximately 20 min at 25 degrees C for the wild type, thus enhancing stability 10(6)-fold. In addition, the three most stabilizing single mutations were transferred to two GDH homologues from Bacillus thuringiensis and Bacillus licheniformis. The thermal stability as measured by half-life and CD(222 nm) of the GDH variants was increased, as expected. The resulting stability changes provide further support for the view that these residues are critical for stability of GDHs and reinforce the success of the consensus approach for identifying stabilizing mutations.

Structure-guided consensus approach to create a more thermostable penicillin G acylase.

The thermostabilization of penicillin G acylase (PGA) is a difficult problem due to the large size of the protein and its complex maturation process. We developed a data-driven protein design method that requires fewer homologous sequences than the traditional consensus approach and utilizes structural information to limit the number of variants created. Approximately 50% of our 21 single-point mutants were found experimentally to be more thermostable than the wild-type PGA, two had almost threefold longer half-life at 50 degrees C, with very little effect on activity. An analysis of four programs that predict the thermostability conferred by point mutations shows little agreement between the programs and with the experimental data, emphasizing that the chosen stabilizing mutations are very difficult to predict, but that our data-driven design method should prove useful.