Resultados de la implementación de una guía de recomendaciones en el cuidado de las personas con ostomías digestivas / Results in the Application of a Recommendation Guide for the Care of People with Digestive Ostomy / Resultados da implementação de diretrizes de recomendações no cuidado de pessoas com ostomias digestivas

Introducción. La instauración de una ostomía digestiva tiene una importante repercusión física y emocional en las personas. El objetivo de este estudio es analizar la adherencia de las enfermeras a las buenas prácticas en el manejo de las ostomías, la disminución de complicaciones y la adquisición de destrezas de los pacientes en su propio autocuidado tras la implementación de la Guía de Buenas Prácticas de la asociación de enfermeras de Ontario. Metodología. Estudio cuasiexperimental prospectivo en una unidad de cirugía digestiva desde 2017 hasta 2022. La intervención ha consistido en la implementación de las recomendaciones de cuidados de una Guía de Buenas Prácticas, analizando variables de proceso y de resultados en la salud a lo largo del proceso. Resultados. Se han encontrado diferencias significativas (p<0.05) en las variables de adherencia: educación sanitaria preoperatoria, marcaje del estoma, evaluación integral posoperatoria y educación sanitaria posoperatoria. No se han encontrado diferencias significativas en las variables de complicaciones del estoma (del 37.5% al 27.8%), ni en las complicaciones de la piel periestomal (del 12.5% al 10.2%). Sí se han encontrado diferencias en la variable de adquisición de destrezas del paciente en su autocuidado (del 44.44% al 98%). Discusión. Implantar recomendaciones de buenas prácticas mejora la calidad de los cuidados y disminuye las complicaciones. Conclusiones. La implementación de la guía ha aumentado la adherencia de las enfermeras a las buenas prácticas basadas en la evidencia y ha mejorado la adquisición de destrezas de los pacientes en su autocuidado, disminuyendo las complicaciones (aunque sin significación). Palabras clave: Estomía; Autocuidado; Guía de Práctica Clínica; Enfermería Basada en la Evidencia; Evaluación de Resultado en la Atención de Salud

Introduction. The establishment of a digestive ostomy has an essential physical and emotional repercussion. This study aims to analyze nurses' adherence to the good practice of management in ostomy, the decrease of complications, and the acquisition of patients' ability in self-care after implementing the Ontario Nurses' Good Practices guide. Methodology. A quasi-experimental prospective study in a digestive surgery unit from 2017 to 2022. The intervention consists of implementing the recommendations made in the Good Practices Guide and analyzing variables of process and health throughout the process. Results. Significative differences have been found (p<0.05) in the adherence variables: preoperatory sanitary education, marking of stoma, post-operatory integral evaluation, and sanitary post-operatory education. The investigators did not find significant differences in the variable of stoma complications (from 37.5% to 27.8%) or the peristoma skin complications (from 12.5% to 10.2%). A difference in the acquisition of abilities of the patient self-care was found (from 44.4% to 98%). Discussion. To make good practice recommendations improves the quality of the care and reduces complications. Conclusions. Implementing the guide has increased the nurses' adherence to the good practices based on the evidence and the acquisition of abilities in the patient's self-care, decreasing the complications (even though it didn't show significance). Keywords: Ostomy; Self Care; Practice Guideline; Evidence-Based Nursing; Outcome Assessment, Health Care

Introdução. A realização de uma ostomia digestiva tem um importante impacto físico e emocional nas pessoas. O objetivo deste estudo é analisar a adesão das enfermeiras às boas práticas no manejo de ostomias, a redução de complicações e a aquisição de habilidades dos pacientes no seu próprio autocuidado após a implementação das diretrizes de boas práticas dos Associação de Enfermeiras de Ontário. Metodologia. Estudo prospectivo quase-experimental numa unidade de cirurgia digestiva de 2017 a 2022. A intervenção consistiu na implementação das recomendações de cuidados das Diretrizes de Boas Práticas, analisando variáveis de processo e resultados de saúde ao longo do processo. Resultados. Foram encontradas diferenças significativas (p<0.05) nas variáveis de adesão: educação em saúde préoperatória, marcação do estoma, avaliação pós-operatória abrangente e educação em saúde pós-operatória. Não foram encontradas diferenças significativas nas variáveis de complicações do estoma (de 37.5% para 27.8%), nem nas complicações da pele periestomal (de 12.5% para 10.2%). Foram encontradas diferenças na variável aquisição de habilidades de autocuidado pelo paciente (de 44.44% para 98%). Discussão. A implementação de recomendações de boas práticas melhora a qualidade dos cuidados e reduz complicações. Conclusões. A implementação das diretrizes aumentou a adesão das enfermeiras às boas práticas baseadas em evidências e melhorou a aquisição de habilidades de autocuidado pelos pacientes, diminuindo complicações (embora não significativamente). Palavras-chave: Estomia; Autocuidado; Guia de Prática Clínica; Enfermagem Baseada em Evidências; Avaliação de Resultados em Cuidados de Saúde

Lessons learnt from the implementation of a colorectal cancer screening programme for lynch syndrome in a tertiary public hospital.

BACKGROUND: Lynch syndrome (LS) is the first cause of inherited colorectal cancer (CRC), being responsible for 2-4% of all diagnoses. Identification of affected individuals is important as they have an increased lifetime risk of multiple CRC and other neoplasms, however, LS is consistently underdiagnosed at the population level. We aimed to evaluate the yield of LS screening in CRC in a single-referral centre and to identify the barriers to its effective implementation. METHODS: LS screening programme included individuals with CRC < 70 years, multiple CRC, or endometrial cancer at any age. Mismatch repair (MMR) protein immunohistochemistry (IHC) analysis was performed in routine practice on the surgical specimen and, if MLH1 IHC was altered, MLH1 gene promoter methylation was analysed. Results were collected in the CRC multidisciplinary board database. LS suspected individuals (altered MMR IHC without MLH1 promoter methylation) were referred to the Cancer Genetic Counselling Unit (CGCU). If accepted, a genetic study was performed. Two checkpoints were included: review of the pathology data and verification of patient referral by a genetic counsellor. RESULTS: Between 2016 and 2019, 381 individuals were included. MMR IHC analysis was performed in 374/381 (98.2 %) CRC cases and MLH1 promoter methylation in 18/21 (85.7 %). Seventeen of the 20 LS suspected individuals were invited for referral at the CGCU. Two cases were not invited and the remaining patient died of cancer before completion of tumour screening. Fifteen individuals attended and a genetic analysis was performed in 15/20 (75 %) LS suspected individuals. Ten individuals were diagnosed with LS, in concordance with the IHC profile (2.7 % of the total cohort). This led to cascade testing in 58/75 (77.3 %) of the available adult relatives at risk, identifying 26 individuals with LS. CONCLUSIONS: Establishing a standardized institutional LS screening programme with checkpoints in the workflow is key to increasing the yield of LS identification.

Time course and predictors for neoaortic root dilatation and neoaortic valve regurgitation during adult life after arterial switch operation.

INTRODUCTION AND OBJECTIVES: There are limited data on the long-term development of neoaortic root dilatation (NRD) and neoaortic valve regurgitation (AR) after arterial switch operation (ASO) for transposition of the great arteries during adult life. METHODS: We performed a retrospective longitudinal analysis of 152 patients older than 15 years who underwent ASO for transposition of the great arteries and who were followed-up for 4.9±3.3 years in 2 referral centers. Sequential changes in body surface-adjusted aortic root dimensions and progression to moderate/severe AR were determined in patients with 2 or more echocardiographic examinations. Risk factors for dilatation were tested by Cox regression to identify predictors of AR progression. RESULTS: At baseline, moderate AR was present in 9 patients (5.9%) and severe AR in 4 (2.6%), of whom 3 had required aortic valve surgery. Initially, the median neoaortic root dimension was 20.05±2.4mm/m2, which increased significantly to 20.73±2.8mm/m2 (P <.001) at the end of follow-up. The mean change over time was 0.14mm/m2/y (95%CI, 0.07-0.2). Progressive AR was observed in 20 patients (13.5%) and 6 patients (4%) required aortic valve surgery. Progressive AR was associated with bicuspid valve, AR at baseline, NRD at baseline, and neoaortic root enlargement. Independent predictors were bicuspid valve (HR, 3.3; 95%CI, 1.1-15.2; P=.037), AR at baseline (HR, 5.9; 95%CI, 1.6-59.2; P=.006) and increase in NRD (HR, 4.1 95%CI, 2-13.5; P=.023). CONCLUSIONS: In adult life, NRD and AR progress over time after ASO. Predictors of progressive AR are bicuspid valve, AR at baseline, and increase in NRD.

microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors.

Venous thromboembolism (VTE) is a common complication of cancer that severely increases morbidity and mortality. Patients with intracranial tumors are more likely to develop VTE than patients with cancers at other sites. Conversely, limited tools exist to identify patients with high thrombotic risk. Upon activation, neutrophils release their content through different mechanisms triggering thrombosis. We explored the ability of microRNAs (miRNAs) and plasma markers of neutrophil activation measured before surgery to predict the risk of early post-surgical pulmonary embolism (PE) in glioma and meningioma patients. We recruited and prospectively followed 50 patients with glioma and 50 with meningioma, 34% of whom in each group developed an early objectively-diagnosed post-surgical PE. We measured miRNA expression and neutrophil markers (cell-free DNA, nucleosomes, calprotectin and myeloperoxidase) before surgery. In glioma patients, we adjusted and validated a predictive model for post-surgical PE with 6 miRNAs: miR-363-3p, miR-93-3p, miR-22-5p, miR-451a, miR-222-3p and miR-140-3p (AUC = 0.78; 95% Confidence Interval (CI) [0.63, 0.94]) and another with cfDNA and myeloperoxidase as predictors (AUC = 0.71; 95%CI [0.52, 0.90]). Furthermore, we combined both types of markers and obtained a model with myeloperoxidase and miR-140-3p as predictors (AUC = 0.79; 95%CI [0.64, 0.94]). In meningioma patients we fitted and validated a predictive model with 6 miRNAs: miR-29a-3p, miR-660-5p, miR-331-3p, miR-126-5p, miR-23a-3p and miR-23b-3p (AUC = 0.69; 95%CI [0.52, 0.87]). All our models outperformed the Khorana score. This is the first study that analyzes the capability of plasma miRNAs and neutrophil activation markers to predict early post-surgical PE in glioma and meningioma patients. The estimation of the thrombotic risk before surgery may promote a tailored thromboprophylaxis in a selected group of high-risk patients, in order to minimize the incidence of PE and avoid bleedings.

Urine metabolomic analysis in clear cell and papillary renal cell carcinoma: A pilot study.

Renal cell carcinoma (RCC) is one of the most lethal type of tumors and is twice more frequent in men than in women. Initial symptoms are unspecific and belated thus increasing mortality. Moreover, current diagnostic and monitoring tools are harmful for the patient and unspecific in low-grade tumors. Therefore, novel minimally-invasive markers are needed to diagnose and monitor RCC patients. Urine represents the ideal sample source of non-invasive biomarkers for RCC. In our study we aimed to identify a urine metabolomic profile characteristic of RCC patients with diagnostic purposes and also to identify a profile with prognostic value. By an UPLC-Q-ToF MS untargeted metabolomic analysis, we compared the metabolomic profile of 23 RCC patients (14 clear cell RCC and 9 papillary RCC) before surgery and that of 23 healthy controls. Additionally, for the first time, we compared the metabolomic profile of these RCC patients pre-nephrectomy and 3 months and one year post-nephrectomy. We identified the dysregulated metabolomic variables by querying their exact mass against those presented in the Metlin and Human Metabolome Database. Next, we experimentally confirmed their identity. Both RCC subtypes showed similar metabolomic patterns at all stages. 51 metabolomic variables were significantly increased in RCC compared to controls and, among them, 4 were selected as potential discriminant metabolites between groups. We could experimentally confirm the identity of p-cresol glucuronide thus describing for the first time an increase in this metabolite in urine of RCC patients (fold change = 2.922, P = .012). Additionally, we confirmed that no metabolomic differences occur 3 months post-nephrectomy in RRC, while 188 variables were significantly increased one year post-nephrectomy. Of the 15 most discriminant metabolomic variables, we could experimentally confirm the identity of isobutyryl-l-carnitine (fold change = 2.098, P = .004) and l-proline betaine (fold change = 3.328, P = .004), for the first time. In summary, we have identified urine p-cresol glucuronide as potential diagnostic marker for RCC and isobutyryl-l-carnitine and l-proline betaine as potential prognostic markers. When confirmed in an independent cohort of RCC patients, these markers may improve the diagnosis and monitoring of RCC patients thus reducing current harmful diagnostic procedures. SIGNIFICANCE: The high-radiation dose of current imaging techniques available to diagnose and monitor renal cell carcinoma (RCC) are harmful for the patient and unspecific in low-grade tumors. Our untargeted metabolomic analysis carried out in urine samples from RCC patients and healthy individual reveals p-cresol glucuronide as potential diagnostic marker for RCC. Additionally, the analysis of RCC urine samples one year post-nephrectomy reveals isobutyryl-l-carnitine and l-proline betaine as potential prognostic markers. These novel non-invasive urine biomarkers may improve RCC management thus reducing the use of current harmful diagnostic techniques.

Urinary microRNAs: Looking for a New Tool in Diagnosis, Prognosis, and Monitoring of Renal Cancer.

PURPOSE OF REVIEW: Renal cell carcinoma (RCC) is the third most common urologic malignancy. First symptoms are usually unspecific and belated causing the stages to be high when diagnosed. As compensation, incidental detection of RCC by abdominal imaging techniques for other medical purposes is a reality that favours a decrease in the stage of new diagnosed tumours. Therefore, identifying novel predictive biomarkers for diagnosis, progression and prognosis of RCC is fundamental. RECENT FINDINGS: To date, several studies have demonstrated that microRNAs (miRNAs) play a role in the particular scenario of urologic tumors, and alterations at miRNA level are involved in the initiation, progression and metastases formation of renal cancer. In the present review, we have summarized the up­to­date preliminary clinical works on the role of urinary miRNA profiling in RCC, including an evaluation of its value as a potential biomarker for diagnosis, prognosis and follow up of RCC patients.

MicroRNAs and Neutrophil Activation Markers Predict Venous Thrombosis in Pancreatic Ductal Adenocarcinoma and Distal Extrahepatic Cholangiocarcinoma.

Cancer-associated venous thrombosis (VTE) increases mortality and morbidity. However, limited tools are available to identify high risk patients. Upon activation, neutrophils release their content through different mechanisms, thereby prompting thrombosis. We explored plasma microRNAs (miRNAs) and neutrophil activation markers to predict VTE in pancreatic ductal adenocarcinoma (PDAC) and distal extrahepatic cholangiocarcinoma (DECC). Twenty-six PDAC and 6 DECC patients recruited at cancer diagnosis, were examined for deep vein thrombosis and pulmonary embolisms, and were then followed-up with clinical examinations, blood collections, and biCUS. Ten patients developed VTE and were compared with 22 age- and sex-matched controls. miRNA expression levels were measured at diagnosis and right before VTE, and neutrophil activation markers (cell-free DNA, nucleosomes, calprotectin, and myeloperoxidase) were measured in every sample obtained during follow-up. We obtained a profile of 7 miRNAs able to estimate the risk of future VTE at diagnosis (AUC = 0.95; 95% Confidence Interval (CI) (0.987, 1)) with targets involved in the pancreatic cancer and complement and coagulation cascades pathways. Seven miRNAs were up- or down-regulated before VTE compared with diagnosis. We obtained a predictive model of VTE with calprotectin as predictor (AUC = 0.77; 95% CI (0.57, 0.95)). This is the first study that addresses the ability of plasma miRNAs and neutrophil activation markers to predict VTE in PDAC and DECC.

A predictive model for prostate cancer incorporating PSA molecular forms and age.

The diagnostic specificity of prostate specific antigen (PSA) is limited. We aimed to characterize eight anti-PSA monoclonal antibodies (mAbs) to assess the prostate cancer (PCa) diagnostic utility of different PSA molecular forms, total (t) and free (f) PSA and PSA complexed to α1-antichymotrypsin (complexed PSA). MAbs were obtained by immunization with PSA and characterized by competition studies, ELISAs and immunoblotting. With them, we developed sensitive and specific ELISAs for these PSA molecular forms and measured them in 301 PCa patients and 764 patients with benign prostate hyperplasia, and analyzed their effectiveness to discriminate both groups using ROC curves. The free-to-total (FPR) and the complexed-to-total PSA (CPR) ratios significantly increased the diagnostic yield of tPSA. Moreover, based on model selection, we constructed a multivariable logistic regression model to predictive PCa that includes tPSA, fPSA, and age as predictors, which reached an optimism-corrected area under the ROC curve (AUC) of 0.86. Our model outperforms the predictive ability of tPSA (AUC 0.71), used in clinical practice. In conclusion, The FPR and CPR showed better diagnostic yield than tPSA. In addition, the PCa predictive model including age, fPSA and complexed PSA, outperformed tPSA detection efficacy. Our model may avoid unnecessary biopsies, preventing harmful side effects and reducing health expenses.

Pediocin-like bacteriocins: new perspectives on mechanism of action and immunity.

This review attempts to analyze the mechanism of action and immunity of class IIa bacteriocins. These peptides are promising alternative food preservatives and they have a great potential application in medical sciences. Class IIa bacteriocins act on the cytoplasmic membrane of Gram-positive cells dissipating the transmembrane electrical potential by forming pores. However, their toxicity and immunity mechanism remains elusive. Here we discuss the role of the mannose phosphotransferase system (man-PTS) as the receptor for class IIa bacteriocins and the influence of the membrane composition on the activity of these antimicrobial peptides. A model that is consistent with experimental results obtained by different researchers involves the non-specific binding of the bacteriocin to the negatively charged membrane of target bacteria. This step would facilitate a specific binding to the receptor protein, altering its functionality and forming an independent pore in which the bacteriocin is inserted in the membrane. An immunity protein could specifically recognize and block the pore. Bacteriocins function in bacterial ecosystems and energetic costs associated with their production are also discussed. Theoretical models based on solid experimental evidence are vital to understand bacteriocins mechanism of action and to promote new technological developments.

Estreñimiento crónico: identificación de las causas en una clínica de manejo intestinal / Chronical Constipation: identification of the causes at a Bowel Management Clinic

Resumen:Antecedentes:el estreñimiento crónico en la población pediátrica es una patología frecuente que puede afectar la calidad de vida del paciente y el entorno familiar. Se presenta la experiencia inicial de la Clínica de Manejo Intestinal, en la que se incluyen pacientes con patologías médicas y quirúrgicas de difícil manejo.Metodología:se revisaron los expedientes clínicos de la Clínica de Manejo Intestinal del Hospital "Dr. Maximiliano Peralta Jiménez", incluyendo todos los pacientes valorados desde junio de 2012 hasta junio de 2015. Se tomaron como pacientes activos, aquellos que se encuentran en control en la clínica, y como resueltos aquellos pacientes que fueron manejados inicialmente y luego referidos a la consulta externa de pediatría o cirugía.Resultados:se obtuvieron 77 pacientes, 25 activos (35%) y 52 resueltos (65%), que fueron referidos de las consultas de Pediatría y Cirugía Pediátrica, por estreñimiento de difícil manejo. De los pacientes activos, los diagnósticos son: 16 pacientes (64%) estreñimiento funcional, 6 pacientes (24%) enfermedad de Hirschsprung, 1 paciente (4%) con Síndrome de Mowat Wilson, 1 paciente con espina bífida, 1 paciente con ptosis del colon transverso. El motivo de consulta de los pacientes activos fue estreñimiento crónico en 20 (80%), enfermedad de Hirschsprung en 3 (12%) y encopresis en 2 pacientes (8%); los síntomas asociados de este grupo de pacientes fueron: dolor abdominal en 10 (40%), vómito en 3 (12%) y manchado en 19 (76%). De los 52 pacientes resueltos, 32 son hombres (61,5 %) y 20, mujeres. 44 pacientes (84,6%) tienen diagnóstico de estreñimiento funcional, 6 (11,5%) de enfermedad de Hirschsprung, 1 (1,9%) de ano imperforado con fístula perineal, y 1 con estenosis anal. El motivo de consulta fue estreñimiento crónico en 47 pacientes (90%), estenosis anal en 1 (1,9%), enfermedad de Hirschsprung en 1 (1,9%), fecalomas en 1 (1,9%), malformación anorrectal en 1 (1,9%) y enfermedad pélvica inflamatoria también en 1 paciente (1,9%).Conclusiones:los resultados obtenidos permiten identificar las causas más frecuentes de referencia de los pacientes con estreñimiento referidos a la Clínica de Manejo Intestinal del Hospital "Dr. Maximiliano Peralta Jiménez". De todos los pacientes referidos por estreñimiento de difícil manejo, se detectaron 15 (19%) de resolución quirúrgica.

Abstract:Background:Chronic constipation in the pediatric population is a common pathology that can affect the quality of life of the patient and the family. The initial experience at the Bowel Management Clinic is presented; patients with medical and surgical pathologies are included.Methodology:the clinical files from the Bowel Management Clinic at the Hospital "Dr. Maximiliano Peralta Jiménez" were reviewed, including all the patients evaluated between June 2012 to June 2015. The patients considered as active, are those who are presently in control at the clinic and patients considered as solved those patients who were evaluated initially and then referred to the pediatric outpatient clinic or surgery.Results:77 patients were included, 25 were active patients (35%) and 52 solved (65%), that were referred from the pediatric and pediatric surgery outpatients clinic for difficult management constipation. In the active patients the diagnoses are: 16 patients (64%) functional constipation, 6 patients (24%) Hirschsprung's disease, 1 patient (4%) with Mowat Wilson's Syndrome, 1 patient with spina bifida and 1 patient with ptosis of the transverse colon. The motive for consultation of the active patients was a chronic constipation in 20 patients (80%), Hirschsprung's disease in 3 (12%) and encopresis in 2 patients (8%); the associated symptoms of this group of patients were: abdominalpain in 10 patients (40%), vomit in 3 patients (12%) and soiling in 19 patients (76%) From the 52 solved patients, 32 are men (61.5%) and 20 women. 44 patients (84.6%) have diagnosis of functional constipation, 6 (11.5%) Hirschsprung's disease, 1 patient (1.9%) imperforated anus with perineal fistula and 1 patient with anal stenosis. The motive for consultation was chronic constipation in 47 patients (90%), anal stenosis in 1 (1.9%), anorectal malformation in 1 (1.9%) and inflammatory pelvic disease also in 1 patient (1.9%).Conclusions:The obtained results allow us to identify the most frequent causes of referral patients with chronic constipation to the Bowel Management Clinic at the Hospital "Dr. Maximiliano Peralta Jiménez". From all the patients referred for constipation of difficult management 15 (19 %) were detected for surgical resolution.

Efectividad de la musicoterapia en la disminución del dolor agudo en pacientes post operados de cirugía laparoscópica en la Unidad de Recuperación Post Anestésica / Effectiveness of music therapy in reducing acute pain in post-operative patients of laparoscopic surgery in the Post Anesthetic Recovery Unit

Planteamiento de problema: El dolor agudo es una de las manifestaciones incómodas que experimenta todo paciente post operado, aparecen en las primeras horas después de la cirugía. Formulación del problema: ¿Es efectiva la musicoterapia en la disminución del dolor agudo en pacientes post operados de cirugía laparoscópica en el servicio de la Unidad de Recuperación Post Anestésica del Hospital Carlos Lanfranco La Hoz 2014? Justificación: Se busca despertar el interés del profesional de enfermería para elaborar estrategias e intervenciones que permitan mejorar las competencias, proponer protocolos de atención incluyendo la musicoterapia como intervención de enfermería al paciente con dolor post operatorio. Objetivos: Objetivo general: Determinar la efectividad de la musicoterapia en la disminución del dolor en pacientes post operados de cirugía laparoscópica en la Unidad de Recuperación Post anestésica del Hospital Carlos Lanfranco La Hoz 2014. Tipo de estudio: El presente estudio de investigación es de Tipo Cuasiexperimental. Ubicación del estudio: El presente estudio se llevará a cabo en el distrito de Puente Piedra, en el servicio de Recuperación del servicio de centro quirúrgico del Hospital Carlos Lanfranco La Hoz. Población: 120 pacientes postoperados de cirugía laparoscópica en un periodo de 3 meses. (AU)

Characterization of variants in the glucosylceramide synthase gene and their association with type 1 Gaucher disease severity.

The extreme phenotypic variability of patients with Gaucher disease (GD) is not completely explained by glucocerebrosidase gene mutations. It has been proposed that genetic modifiers might influence GD phenotype. We examined seven polymorphisms of the glucosylceramide synthase gene (UGCG) and their correlation with severity of GD. Five UGCG variants were significantly associated with disease severity, according to the DS3 scoring system: c.-295C>T, c.-232_-241ins10, c.98+50A>G, c.98+68A>T, and c.861A>G. Heterozygous [N370S]+[L444P] patients with c.[-232_-241ins10;98+50G] haplotype had a significantly lower DS3 score in relation to patients carrying only one of these polymorphisms. Electrophoretic mobility shift assay analysis showed an increased nuclear protein binding ability for the G allele at the cDNA position c.98+50, as well as an altered pattern for the c.-232_-241ins10 allele. The promoter activity of the haplotypes decreased significantly with respect to wild type activity in HepG2 and COS-7 cells (-14% and -16% for the c.[-232_-241ins10;98+50A] haplotype, -44% and -25% for c.[-222nonins;98+50G] haplotypes, and -64% and -75% for c.[-232_-241ins10;98+50G] haplotype, respectively). These data indicate that the c.-232_-241ins10 and c.98+50A>G variants are modifying factors of GD severity, which can partly explain the variability in severity of the disease.

[Drug consumption and perception among Latin American immigrants]. / Consumo de drogas y su percepción por parte de inmigrantes latinoamericanos.

The aim of this study is to obtain information about drug consumption, leisure activities and knowledge of community services among Spanish-speaking immigrants to prevent drug abuse in this population. Quantitative methodology was used. The field work of this study has two phases: in the first stage (2003), a survey of social perception of drugs was administered to 147 subjects. During the second stage (2004), 610 surveys were administered. Data were analysed by bivariate analysis. Usual consumption of alcohol was 40.1%, usual consumption of tobacco was 31.3%, and usual consumption of cannabis was 3.4%. Drug users considered that the main reason for drug consumption was "to have fun" (p<.03). There is a relationship between leisure time and drug use. Family plays an important role in drug abuse prevention and preventive drug abuse programs must be adapted to this population.

The role of protein C inhibitor in human reproduction.

Protein C inhibitor (PCI) is a heparin-dependent serine protease inhibitor found in human plasma, urine, and other body fluids. In blood plasma, PCI is present at approximately 0.08 microM and inactivates activated protein C and other coagulation and fibrinolytic enzymes. In seminal plasma, PCI is present at 2.2 to 3.7 microM. The main sources of seminal PCI are the seminal vesicles, where it remains fully active. Following ejaculation, PCI completely looses its activity in approximately 2 hours, when it partially complexes with prostate-specific antigen, two plasminogen activators (urokinase-type and tissue-type plasminogen activators), and tissue kallikrein. PCI is also present in an active form in follicular fluid at approximately 0.1 microM. Purified functionally active human blood plasma-derived as well as inactive semen-derived PCI inhibited both binding and penetration of zona-free hamster oocytes by human sperm. The binding inhibition by PCI was dose dependent. A concentration of 0.04 microM PCI (approximately 100-fold lower than that present in seminal plasma) inhibited 50% of the binding and penetration ability. Given that capacitated sperm used for in vitro fertilization usually contains more than 0.05 microM of PCI, fertilization rates might be significantly reduced. All of these data suggest that PCI is involved in human reproduction at several steps, including the fertilization process.

Mecanismo de acción de los hongos entomopatógenos / Mechanism of action of entomopathogenic fungi

Los hongos entomopatógenos tienen un gran potencial como agentes de control, ya que constituyen un grupo con más de 750 especies que al dispersarse en el ambiente provocan infecciones fúngicas en las poblaciones de insectos. Estos hongos inician su proceso infectivo cuando las esporas son retenidas en la superficie del integumento, donde se inicia la formación del tubo germinativo, comenzando el hongo a excretar enzimas como las proteasas, quitinasas, quitobiasas, lipasas y lipooxigenasas. Estas enzimas degradan la cutícula del insecto y coadyuvan con el proceso de penetración por presión mecánica iniciado por el apresorio, que es una estructura especializada formada en el tubo germinativo. Una vez dentro del insecto, el hongo se desarrolla como cuerpos hifales que se van diseminando a través del hemocele e invaden diversos tejidos musculares, cuerpos grasos, tubos de Malpighi, mitocondrias y hemocitos, ocasionando la muerte del insecto después de 3 a 14 días de iniciada la infección. Una vez muerto el insecto y ya agotados muchos de los nutrientes, el hongo inicia un crecimiento micelar e invade todos los órganos del hospedero. Finalmente, las hifas penetran la cutícula desde el interior del insecto y emergen a la superficie, donde en condiciones ambientales apropiadas inician la formación de nuevas esporas

Procura de hígado para transplante hépatico ortotópico: comparación entre dos técnicas / Liver procurement for orthotopic liver transplantation: comparison between two techniques

Diversas modificaciones a la técnica convencional de procura del hígado en donantes cadavéricos con perfusión aórtica y portal (PAP), han sido propuestas para simplificar el procedimiento. La técnica de perfusión aórtica exclusiva (PAE), evita la disección del hilio hepático y extrae en bloque el injerto. Nuestro objetivo es comparar los resultados obtenidos con la aplicación de ambas técnicas de procuramiento. Métodos: Entre marzo - 1994 y octubre - 2002, fueron realizados 32 procuramientos hepáticos consecutivos: 16 (50 por ciento) con la técnica de PAE. Se comparó retrospectivamente datos demográficos de donantes, tiempos de isquemia /operatorios, volumen de solución preservante utilizada, biopsias de reperfusión, causas de injertos descartados, frecuencia de procedimientos a distancia y sobrevida de injerto y paciente. Resultados: No hubo diferencias en edad, sexo y causas de muerte encefálica de los donantes. Los tiempos promedios (SEM) de isquemia total fueron similares en ambos grupos. Los tiempos operatorios fueron: PAE: 117,4 (2,9) vs PAP: 186,7 (8,9) min (p<0,0001) y el volumen perfundido de solución preservante fue: PAE: 4.800 (168) vs PAP: 5.563 (128) ml(p<0,001). No hubo diferencias en las biopsias de reperfusión. Procuras a distancia (>100 KM) se realizaron en 12,5 por ciento de los casos de PAP y en 43,8 Por ciento de los donantes con PAE (p<0,05). Hubo un caso de falla primaria del injerto en el grupo de PAP. La sobrevida al año de injerto y paciente fue similar en ambos grupos. Conclusión: La procura del hígado del donante con la técnica de PAE es segura, más rápida y economiza solución preservante.

The role of the complexed-to-total prostate-specific antigen ratio in predicting the final pathological stage of clinically localized prostate cancer.

OBJECTIVES: To examine the association between the complexed-to-total (C:T) prostate-specific antigen (PSA) ratio and prostate cancer pathological stage to assess whether the C:T PSA ratio may predict the final pathological stage in patients with clinically localized prostate cancer. PATIENTS AND METHODS: In a prospective study, 101 men with clinically localized prostate cancer underwent a staging pelvic lymphadenectomy and radical prostatectomy. Total PSA (tPSA) and PSA complexed to alpha(1)-antichymotrypsin (cPSA) were measured from preoperative plasma and were correlated with the clinical and pathological stage, and with surgical margin status. The pathological stage was determined as organ-confined (n=59) and extracapsular extension (n=42). RESULTS: The distributions of tPSA and cPSA were significantly different in men with locally confined and those with locally extended disease. This finding was not observed for the C:T PSA ratio. The area under the receiver operating characteristic (ROC) curve to predict the final pathological stage was significantly greater for tPSA (0.684) and cPSA (0.677) than for the C:T PSA ratio (p<0.032). TPSA (0.685) and cPSA (0.670) also showed areas under the ROC curve greater than that of the C:T PSA ratio (0.542) (p<0.05) for prediction of positive surgical margins. CONCLUSIONS: Our results show that the C:T PSA ratio does not improve the performance of total PSA for predicting the final pathological stage in patients with clinically localized prostate cancer.

The proportion of prostate-specific antigen (PSA) complexed to alpha(1)-antichymotrypsin improves the discrimination between prostate cancer and benign prostatic hyperplasia in men with a total PSA of 10 to 30 microg/L.

BACKGROUND: The aim of this study was to assess the diagnostic accuracy of the proportion of prostate-specific antigen (PSA) complexed to alpha(1)-antichymotrypsin (PSA-alpha(1)ACT:PSA ratio) in the differential diagnosis of prostate cancer (CaP) and benign prostatic hyperplasia (BPH) in men with total PSA of 10-30 microg/L. METHODS: We used our immunoassays (ELISAs) for total PSA and PSA-alpha(1)ACT complex to study 146 men. In 123, total PSA was between 10 and 20 microg/L; 66 of these had CaP and 57 BPH. In 23 men, total PSA was between 20 and 30 microg/L; 14 of these had CaP and 9 BPH. We calculated the area under the ROC curves (AUC) for total PSA, PSA-alpha(1)ACT complex, and PSA-alpha(1)ACT:PSA ratio, and determined the cutoff points that gave sensitivities approaching 100%. RESULTS: In the total PSA range between 10 and 20 microg/L, the AUC was significantly higher for the PSA-alpha(1)ACT:PSA ratio (0.850) than for total PSA (0.507) and PSA-alpha(1)ACT complex (0.710; P <0.0001). A cutoff ratio of 0.62 would have permitted diagnosis of all 66 patients with CaP (100% sensitivity) and avoided 19% of unnecessary biopsies (11 of 57 patients). In the total PSA range between 20 and 30 microg/L, the AUC for the PSA-alpha(1)ACT:PSA ratio (0.980; 95% confidence interval, 0.82-0.99) was greater than the AUC for total PSA (0.750; 95% confidence interval, 0.51-0.89; P = 0.042). In this range, a cutoff point of 0.64 would have permitted the correct diagnosis of all 14 patients with CaP and 6 of the 9 with BPH. CONCLUSIONS: The diagnostic accuracy of the PSA-alpha(1)ACT:PSA ratio persists at high total PSA concentrations, increasing the specificity of total PSA. Prospective studies with large numbers of patients are needed to assess whether the ratio of PSA-alpha(1)ACT to total PSA is a useful tool to avoid unnecessary prostatic biopsy in patients with a total PSA >10 microg/L.