Controlling cleaning agent residues in pharmaceutical manufacturing: A harmonized scientific strategy.

This paper proposes a scientifically justified and harmonized strategy to control cleaning agent ingredients' (CAIs) residues in pharmaceutical manufacturing. Firstly, we demonstrate that worst-case cleaning validation calculations on CAI residues with representative GMP standard cleaning limits (SCLs) are enough to control CAI residues of low concern to safe levels. Secondly, a new harmonized strategy for the toxicological assessment of CAI residues is presented and validated. The results establish a framework applicable to cleaning agent mixtures based on hazard and exposure considerations. This framework is primarily based on the hierarchy of a single CAI's critical effect, where the lowest resulting limit may become the driver of the cleaning validation process. The six critical effect groups are: (1) CAIs of low concern based on safe exposure reasoning; (2) CAIs of low concern based on the mode of action reasoning; (3) CAIs with local concentration-dependent critical effects; (4) CAIs with dose-dependent systemic critical effects for which a route-specific PDE should be calculated; (5) poorly characterized CAIs with unknown critical effect for which a default value of 100 µg/day is proposed; (6) poorly characterized CAIs which should be avoided because of potential mutagenicity and/or potency.

Resultados clínicos según el tiempo de inicio de la ventilación invasiva en niños con fracaso de la ventilación no invasiva / Clinical outcomes according to timing to invasive ventilation due to noninvasive ventilation failure in children

Objetivo En adultos el fracaso de la ventilación no invasiva (VNI) se ha asociado a peores resultados clínicos debido al retraso en la intubación y en el inicio de la ventilación invasiva (VMI). Existe falta de evidencia de esta asociación en pediatría. Nuestro objetivo fue determinar la asociación entre la duración de la VMI y la estancia, con la duración de la VNI previo a la intubación/VMI en pacientes pediátricos. Diseño Estudio de cohorte prospectivo desde enero de 2015 a octubre de 2019. Ámbito Unidad de cuidados intensivos pediátricos (UCIP). Pacientes Niños/as menores de 15años con insuficiencia respiratoria aguda (IRA) que fracasaron a la VNI. Intervenciones Ninguna. Variables de interés principales Se registraron variables demográficas y clínicas, índice de mortalidad pediátrica (PIM2), diagnóstico de síndrome de distrés respiratorio agudo pediátrico (SDRAP), duración de la VMI y la VNI, estancia en UCIP y mortalidad intrahospitalaria. Resultados Se incluyeron un total de 109 pacientes con una mediana de edad de 7 (3-14) meses. El diagnóstico principal fue neumonía (89,9%). El 37,6% de la muestra presentó SDRAP. No se encontró asociación entre duración de la VNI y duración de la VMI mediante el análisis de Kaplan-Meier (logrank test p=0,479). No se encontraron diferencias significativas entre la estancia en UCIP (p=0,253) y hospitalaria (p=0,669) al categorizar por duración de la VNI. El SDRAP se asoció a mayor duración de la VMI (HR: 0,64 [IC95%: 0,42-0,99]). Conclusión No se encontró asociación entre la duración de la VNI previo a la intubación y la duración de la VMI, ni en la estancia en pacientes pediátricos con IRA (AU)

Objective Noninvasive ventilation (NIV) failure it has been associated to worst clinical outcomes due to a delay in intubation and initiation of invasive mechanical ventilation (IMV). There is a lack of evidence in pediatric patients regarding this topic. The objective was to determine the association between duration of IMV and length of stay, with duration of NIV prior to intubation/IMV in pediatric patients. Design A prospective cohort study since January 2015 to October 2019. Setting A pediatric intensive care unit. Patients Children under 15years with acute respiratory failure who failed to noninvasive ventilation. Interventions None. Main variables of interest Demographic variables, pediatric index of mortality (PIM2), pediatric acute respiratory distress syndrome (PARDS) diagnosis, IMV and NIV duration, PICU LOS were registered and intrahospital mortality. Results A total of 109 patients with a median (IQR) age of 7 (3-14) months were included. The main diagnosis was pneumonia (89.9%). PARDS was diagnosed in 37.6% of the sample. No association was found between NIV duration and duration of IMV after Kaplan-Meier analysis (Log rank P=.479). There was no significant difference between PICU LOS (P=.253) or hospital LOS (P=0.669), when categorized by NIV duration before intubation. PARDS diagnosis was associated to an increased length of invasive ventilation (HR: 0.64 [95%IC: 0.42-0.99]). Conclusions No association was found between NIV duration prior to intubation and duration of invasive ventilation in critical pediatric patients with acute respiratory failure (AU)

Clinical outcomes according to timing to invasive ventilation due to noninvasive ventilation failure in children.

OBJECTIVE: Noninvasive ventilation (NIV) failure it has been associated to worst clinical outcomes due to a delay in intubation and initiation of invasive mechanical ventilation (IMV). There is a lack of evidence in pediatric patients regarding this topic. The objective was to deter-mine the association between duration of IMV and length of stay, with duration of NIV prior tointubation/IMV in pediatric patients. DESIGN: A prospective cohort study since January 2015 to October 2019. SETTING: A pediatric intensive care unit. PATIENTS: Children under 15 years with acute respiratory failure who failed to noninvasive ventilation. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Demographic variables, pediatric index of mortality (PIM2), pediatric acute respiratory distress syndrome (PARDS) diagnosis, IMV and NIV duration, PICU LOS were registered and intrahospital mortality. RESULTS: A total of 109 patients with a median (IQR) age of 7 (3-14) months were included. The main diagnosis was pneumonia (89.9%). PARDS was diagnosed in 37.6% of the sample. No association was found between NIV duration and duration of IMV after Kaplan-Meier analysis (Log rank P = .479). There was no significant difference between PICU LOS (P = .253) or hospital LOS (P = 0.669), when categorized by NIV duration before intubation. PARDS diagnosis was associated to an increased length of invasive ventilation (HR: 0.64 [95% IC: 0.42-0.99]). CONCLUSIONS: No association was found between NIV duration prior to intubation and duration of invasive ventilation in critical pediatric patients with acute respiratory failure.

PDE concept for controlling cleaning agent residues in pharmaceuticals- A critical analysis.

Cleaning agents (CAs) are used in multipurpose facilities to control carryover contamination of active pharmaceutical ingredients (APIs) to scientifically justified limits. While this is often done with the PDE methodology used for API impurities, it is unclear if it is justifiable and necessary for cleaning agents, which generally represent a comparatively lower health risk. Comparing calculated oral PDE values for CA ingredients (CAIs) from four companies with PDEs of a selected number of small-molecule APIs showed that the toxicity of CAIs is several orders of magnitude lower. Furthermore, a critical review of the toxicity and everyday exposure to the general population of the main CAIs functional groups showed that the expected health risks are generally negligible. This is particularly true if the associated mode of actions cause local toxicity that is usually irrelevant at the concentration of potential residue carryover. This work points towards alternative approaches to the PDE concept to control CAIs' contamination and provides some guidance on grouping and identifying compounds with lower health risks based on exposure and mode of action reasoning. In addition, this work supports the concept that limit values should only be set for CAIs of toxicological concern.

Desafío diagnóstico y terapéutico de carcinoma mucoepidermoide palatino: reporte de un caso

Resumen Las neoplasias en glándulas salivales son infrecuentes, representando menos del 3% de los tumores de cabeza y cuello. El carcinoma mucoepidermoide es el tumor maligno más común en glándulas salivales, siendo su principal ubicación la parótida. Clínicamente se asemeja a otras lesiones de mucosa oral, por lo cual, es importante realizar un correcto diagnóstico diferencial. Su comportamiento biológico se relaciona con el grado histológico tumoral, factor relevante en el pronóstico y tratamiento de esta neoplasia. Presentamos el caso de un paciente hombre de 75 años afectado con un tumor en paladar con diagnóstico de carcinoma mucoepidermoide de bajo grado. Como tratamiento se realizó una maxilectomía parcial y una placa obturadora en base a una prótesis removible y posterior reconstrucción con un colgajo libre microvascularizado. Actualmente el paciente se encuentra en controles periódicos, libre de enfermedad. Los tumores de glándulas salivales son un desafío diagnóstico, requieren de exámenes imagenológicos y del estudio histopatológico. Cuando existen dudas en el diagnóstico, se debe considerar repetir la toma de la muestra o la obtención de biopsias de más de una zona representativa que permita el diagnóstico de la lesión.

Abstract Salivary gland neoplasms are infrequent lesions representing less than 3% of head and neck tumors. Mucoepidermoid carcinoma is the most common malignant tumor in salivary glands, being the parotid the most usual location. Clinically, it resembles other oral mucosa lesions, therefore, it is important to make a correct differential diagnosis. Its biological behavior is related to the tumor histological grade, a relevant factor in the prognosis and treatment of this neoplasm. We reported a case of a 75-year-old-man, with a tumor in the palate, diagnosed as low-grade mucoepidermoid carcinoma. A partial maxillectomy and an obturator plate were performed based on a removable prosthesis and subsequent reconstruction with a microvascularized free flap. The patient is currently undergoing regular checkups, maintaining disease free. Salivary gland tumors are a diagnostic challenge, requiring imaging tests and histopathological study. In case of doubts with the diagnosis, it should be considered to biopsy more than area or to repeat the biopsy in order to obtain a representative sample that allows the diagnosis of the lesion.

Manejo Quirúrgico de Múltiples Condilomas de la Mucosa Oral en Paciente Bajo Terapia Antirretroviral de Gran Actividad / Surgical Management of Multiple Condylomas in the Oral Mucosa in Patient Undergoing Highly Active Antiretroviral Therapy

RESUMEN: El objetivo de este estudio fue reportar un caso clínico donde se realizó el manejo quirúrgico de múltiples condilomas de la mucosa oral en un paciente infectado por Virus de Inmunodeficiencia Humana (VIH) bajo Terapia Antirretroviral de Gran Actividad (TARGA). Hombre de 58 años en tratamiento por infección con VIH en TARGA hace 17 años, que acude al Servicio de Cirugía Maxilofacial del Hospital Barros Luco-Trudeau con múltiples lesiones verruciformes ubicadas en margen y cara dorsal de lengua, cara interna de ambas mejillas y labio inferior. Se realizó escisión quirúrgica de las lesiones de labio, cara dorsal de lengua y cara interna de mejilla del lado derecho, obteniéndose el diagnóstico histopatológico de condiloma. Tras 2 meses de realizar la cirugía se obtuvo recurrencia. La recurrencia de las lesiones puede originarse por la recrudescencia del virus latente adyacente al lecho quirúrgico y, por ello, deben considerarse otras alternativas de tratamiento. Por el impacto en la función, estética, potencial de contagio y malignización, es necesario su tratamiento.

ABSTRACT: The objective of this study was to report a clinical case in which surgical management of multiple condylomas in the oral mucosa was performed in a patient infected by Human Immunodeficiency Virus (HIV) who is under highly active antiretroviral therapy (HAART). A 58-yearold man, under HAART for 17 years for HIV infection, was admitted at the Maxillofacial Surgery Service at the Hospital Barros Luco-Trudeau as he was experiencing multiple verrucous lesions located on the lateral margin and dorsum of the tongue, as well as on the inner face of both cheeks and the lower lip. A surgical excision of the lesions on the lip, dorsum of the tongue and inner face of the right cheek was performed, where the histopathological diagnosis of condyloma was obtained. There was a recurrence two months after surgery. Recurrence of the lesions may be due to the recrudescence of the latent virus adjacent to the surgical bed and, therefore, other treatment alternatives should be considered. Treatment is necessary due to the impact on the function, aesthetics, and the potential to become contagious and malignant.

Exocrine pancreas glutamate secretion help to sustain enterocyte nutritional needs under protein restriction.

Glutamine (Gln) is the most concentrated amino acid in blood and considered conditionally essential. Its requirement is increased during physiological stress, such as malnutrition or illness, despite its production by muscle and other organs. In the malnourished state, Gln has been suggested to have a trophic effect on the exocrine pancreas and small intestine. However, the Gln transport capacity, the functional relationship of these two organs, and the potential role of the Gln-glutamate (Glu) cycle are unknown. We observed that pancreatic acinar cells express lower levels of Glu than Gln transporters. Consistent with this expression pattern, the rate of Glu influx into acinar cells was approximately sixfold lower than that of Gln. During protein restriction, acinar cell glutaminase expression was increased and Gln accumulation was maintained. Moreover, Glu secretion by acinar cells into pancreatic juice and thus into the lumen of the small intestine was maintained. In the intestinal lumen, Glu absorption was preserved and Glu dehydrogenase expression was augmented, potentially providing the substrates for increasing energy production via the TCA cycle. Our findings suggest that one mechanism by which Gln exerts a positive effect on exocrine pancreas and small intestine involves the Gln metabolism in acinar cells and the secretion of Glu into the small intestine lumen. The exocrine pancreas acinar cells not only avidly accumulate Gln but metabolize Gln to generate energy and to synthesize Glu for secretion in the pancreatic juice. Secreted Glu is suggested to play an important role during malnourishment in sustaining small intestinal homeostasis. NEW & NOTEWORTHY Glutamine (Gln) has been suggested to have a trophic effect on exocrine pancreas and small intestine in malnourished states, but the mechanism is unknown. In this study, we suggest that this trophic effect derives from an interorgan relationship between exocrine pancreas and small intestine for Gln-glutamate (Glu) utilization involving the uptake and metabolism of Gln in acinar cells and secretion of Glu into the lumen of the small intestine.

Incidencia de un programa de actividad física sobre los parámetros antropométricos y la condición física en mujeres mayores de 60 años / Effect of a physical activity program on the anthropometric and physical fitness of women over 60 years

El presente trabajo quiere determinar la incidencia de doce semanas de actividad física sobre la capacidad física y morfología de mujeres mayores de 60 años sin discapacidad de la comuna de Iquique, Chile. Antes y después del periodo de intervención se determinaron las características antropométricas y el estado de condición física de la muestra. Las variables antropométricas evaluadas fueron el peso, talla y perímetros de cintura y cadera. El índice de Masa Corporal (IMC) y de Cintura Cadera (ICC) fue determinado. Para la evaluación del estado de la condición física se empleó el test de dinamometría manual, de salto vertical con contramovimiento y de sentarse y levantarse para la evaluación del estado de la fuerza. El equilibrio se testó mediante el test de equilibrio monopodal con referencia visual y la flexibilidad, mediante el test de flexión anterior del tronco (sit and reach test). Los resultados obtenidos muestran un efecto positivo del programa de intervención sobre el rendimiento de todos los test físicos (p < 0,05). Los parámetros antropométricos mostraron una reducción en el índice cintura-cadera (p = 0,029) y del perímetro de cintura (p=0,014), sin que el resto de las variables analizadas mostraran cambios de interés. De entre las asociaciones observadas, el test de salto vertical mostró una correlación negativa con el test de equilibrio y con el test de de sentarse y levantarse tanto antes como después del tratamiento (R = -0,495; R = -0,699 en el PREtest y R = -0,373; R= -0,463 en el POST para la relación CMJ y Equilibrio y CMJ y Ln S-L test respectivamente, P < 0,05). Se puede concluir que un Programa de actividad física de 12 semanas de duración, mejora la capacidad física (equilibrio, fuerza de prensión manual, fuerza de piernas y flexibilidad anterior de tronco) y los parámetros antropométricos (índice cintura-cadera y perímetro de cintura), en mujeres sanas mayores de 60 años de la comuna de Iquique, Chile (AU)

This paper wants to determine the incidence of twelve weeks of physical activity on physical capacity and morphology of women over 60 yrs without disabilities in the district of Iquique, Chile. Before and after the intervention period was determined anthropometric characteristics and physical fitness status of the sample. Anthropometric variables were weight, height and waist and hip circumferences. The Body Mass Index (BMI) and Waist Hip was determined. To evaluate the status of the physical condition was used handgrip dynamometry test, countermovement vertical jump and get in and out. The balance was tested through the test of visual reference monopodal balance and flexibility through the test of trunk flexion (sit and reach test). Results show a positive effect of the intervention program on the performance of every physical test (p < 0.05). Anthropometric parameters showed a reduction in waist-hip ratio (p = 0.029) and waist circumference (p = 0.014), without rest of the variables analyzed showed changes of interest. Among the observed associations, vertical jump test showed a negative correlation with balance test and getting in and out test, both before and after treatment (R = -0.495, R = -0.699 in PREtest and R = -0.373, R = -0.463 at the POSTtest for the CMJ relation and balance and CMJ and Ln S-L test respectively, P < 0.05). In conclusion, a program of physical activity lasting 12 weeks, improves physical capacity (balance, grip strength, leg strength and flexibility) and anthropometric parameters (waist-hip ratio and waist circumference), in healthy women over 60yrs of the district of Iquique, Chile (AU)

[Effect of a physical activity program on the anthropometric and physical fitness of women over 60 years]. / Incidencia de un programa de actividad física sobre los parámetros antropométricos y la condición física en mujeres mayores de 60 años.

This paper wants to determine the incidence of twelve weeks of physical activity on physical capacity and morphology of women over 60 yrs without disabilities in the district of Iquique, Chile. Before and after the intervention period was determined anthropometric characteristics and physical fitness status of the sample. Anthropometric variables were weight, height and waist and hip circumferences. The Body Mass Index (BMI) and Waist Hip was determined. To evaluate the status of the physical condition was used handgrip dynamometry test, countermovement vertical jump and get in and out. The balance was tested through the test of visual reference monopodal balance and flexibility through the test of trunk flexion (sit and reach test). Results show a positive effect of the intervention program on the performance of every physical test (p < 0.05). Anthropometric parameters showed a reduction in waist-hip ratio (p = 0.029) and waist circumference (p = 0.014), without rest of the variables analyzed showed changes of interest. Among the observed associations, vertical jump test showed a negative correlation with balance test and getting in and out test, both before and after treatment (R = -0.495, R = -0.699 in PREtest and R = -0.373, R = -0.463 at the POSTtest for the CMJ relation and balance and CMJ and Ln S-L test respectively, P < 0.05). In conclusion, a program of physical activity lasting 12 weeks, improves physical capacity (balance, grip strength, leg strength and flexibility) and anthropometric parameters (waist-hip ratio and waist circumference), in healthy women over 60yrs of the district of Iquique, Chile.

La función de atención interferida por una configuración específica de la escena primaria en la mente materna / The role of attention: interfered by a specific primal scene's configuration in the mother's mind

Este trabajo tiene como objetivo central, investigar acerca de la incidencia que tendría en el desarrollo de una alteración severa en la función de atención, específicamente aquella que se manifiesta en la forma de una desconexión de un quedarse en blanco, la configuración mental de la mente materna, en términos de si ésta incluiría o no, de manera significativa, la presencia de un tercero.El valor de dicha posible conexión, sería contar con un signo visible de la existencia de un proceso mudo, soterrado, de defusión pulsional, en sus diferentes niveles de gravedad.El autor, desde el relato de un material clínico, establece nexos con algunos planteamientos teóricos, provenientes desde diferentes vértices metapsicológicos, entre los que resalta la revisión que hace A. Green de los planteamientos de S. Freud, en relación a la dualidad pulsional y entre otros autores, los señalamientos que hace D. Winnicott a esta área de investigación

The main objective of this work is to investigate configuration in the maternal mind impact on the development of attention function severe disruption which manifest specifically in the disconnection, "go into oblivion", in terms of whether or not there is a significative inclusion of a third presence. The value of this possible connection would be a visible sign of a mute, buried process in diffusion drive, at different levels of severity. The author, from clinical material, provides links to different met psychological theoretical approaches in which André Green’s revision of Freud’s arguments about duality drives and Winnicott’s research in this area are stands out

Tumores paratesticulares un diagnóstico inusual: Hospital Clínico San Borja Arriarán / Paratesticular tumors unusual diagnosis: Hospital Clínico San Borja Arriarán

Introducción: El cáncer testicular representa entre el 1,5 por ciento de los cánceres en varones y el 5 por ciento de los tumores urológicos en general. Los tumores paratesticulares representan el 4 por ciento de los tumores testiculares. Material y Método: Se revisaron informes de anatomía patológica y las fichas clínicas de pacientes con diagnóstico de patología testicular durante el período entre enero de 2004 a marzo de 2009. Se analizaron las siguientes variables: edad, testículo involucrado, tipo histológico y tratamiento. Objetivo: Es describir los tumores paratesticulares diagnosticados en el Servicio de Urología del Hospital Clínico San Borja Arriarán. Resultado: Se revisaron 149 casos, de los cuales 110 casos se confirmaron como tumores testiculares. Los tumores germinales representan el 90 por ciento. Los demás tipos histológicos, tres corresponden a metástasis testiculares, dos linfomas y una leucemia. Sólo cuatro casos correspondían a tumores paratesticulares representando el 3,6 por ciento de los tumores tratados. La descripción histológica de los tumores encontrados fue de dos Sarcomas (Rabdomiosarcoma y fibrosarcoma), Hemangiopericitoma y un Linfoma. La mediana de edad es de 62 años. El promedio de evolución de las lesiones fue de 5 meses. Discusión: Las neoplasias paratesticulares del cordón espermático son raras y representan sólo el 4 por ciento de los tumores testiculares. Los más frecuentes son tumores benignos en 2/3 de los casos, siendo el lipoma el tipo histológico más común. Conclusión: Los tumores paratesticulares son neoplasias infrecuentes. La presentación clínica no varía respecto a los demás tumores testiculares excepto en los pacientes inmunodeprimidos.

Introduction: Testicular cancer accounts for 1.5 per cent of cancers in men and 5 per cent of general urologic tumors. Paratesticular tumors represent 4 per cent of testicular tumors. Materials and Methods: We reviewed pathology reports and clinical records of patients diagnosed with testicular pathology during the period January 2004 to March 2009. We analyzed the following variables: age, testicular involvement, histological type and treatment. Aim: You describe paratesticular tumors diagnosed in the urology department of Hospital San BorjaArriarán. Results: We reviewed 149 cases, of which 110 cases were confirmed as malignancy. Germ cell tumors account for 90 percent. Other histologic types, three correspond to metastatic testicular, two lymphomas and leukemia. Only four cases were paratesticular tumors accounting for 3.6 per cent of treated tumors. The histological description of the tumors found were two sarcomas (rhabdomyosarcoma and fibrosarcoma), hemangiopericytoma and a lymphoma. The median age was 62 years. The average evolution of lesions was 5 months. Discussion: Paratesticular neoplasms of the spermatic cord are rare and represent only 4 per cent of testicular tumors. The most common are benign tumors in 2/3 of cases, the lipoma being the most common histologic type. Conclusion: Paratesticular tumors are rare neoplasms. The clinical presentation varies in relation to other testicular tumors except in immunosuppressed patients.

Evaluación de control de calidad, gestión y costos del hemograma en un hospital complejo tipo 1 / Evaluation of hemogram quality control, management and cost in a complex hospital type 1

Determinar criterios de evaluación morfológica del hemograma, basados en parámetros clínicos y resultados del contador hematológico, en términos de gestión, costos y clínica en un hospital tipo 1. Pacientes, materiales y métodos: muestras de hemogramas de pacientes del hospital de carabineros de Chile durante el mes de agosto de 2009, analizadas en un equipo HMX Beckman-Coulter y evaluadas morfológicamente por Tecnólogo Médico(TM). Se registraron parámetros clínicos como hemoglobina, leucocitos y plaquetas; además se consideró el lugar de derivación, especialidad y edad del paciente. Se determinaron los costos e ingresos en función de los resultados obtenidos. Resultados: de los 2.222 pacientes evaluados, existió concordancia entre el Tecnólogo Médico y el analizador en 93,3 por ciento de los casos, con una sensibilidad de 97,3 por ciento y una especificidad de 88,9 por ciento con valores predictivos positivo y negativo de 95,9 por ciento y 92,7 por ciento respectivamente, para detectar una muestra anormal. Con los criterios de selección fue posible eliminar la evaluación morfológca en 79,5 por ciento de los casos, permitiendo un ahorro de $3655929 en el mes por concepto de hemogramas. Discusión: el estudio demostró que es posible disminuir el número de evaluaciones morfológicas realizadas al hemograma a valores similares obtenidos en estudios internacionales, con reducción significativa de los costos y tiempos de TM.

Objective: to determine criteria for the morphological analysis of the full blood count, based on the clinical parameters and the results of the full blood count using an automatic counter in terms of cost and clinicla implications in a distric hospital. Patients, Materials and Method: Full blood count samples from patients attended in the Hospital de Carabineros de Chile during the month of August 2009 were analyzed using HmX Beckman-Coulter and evaluated morpholigically by the Medical Science Officer(Medical Technologist). Clinical parameters, hemoglobin, white cell count platete count were registered, as well the origin of the specimen, medical speciality an patient age. The cost an income derived from the full blood count were determined by the Unit of Cost, Hospital of Carabineros and the changes in costs calculated in function of the results obtained. Results: Of the 2,222 patients evaluated, there was a concordance between the Clinical Science Officer(Medical Technologist) and the automatic counter in 93,9 percent of the samples, with a sensitivity of 97,3 percent and a specificy of 88,9 percent, a positive and negative predictive evalues of 95,9 percent and 92,7 percent respectively for detecting an abnormal sample. Using the criteria of selection it was possible to eliminate the evaluation morphological in 79,5 percent of the samples permitting a saving of $3655929 per month for the analysis of full morphological evaluations of the blood count without losing clinically important data in 80 percent of the samples, which is similar to that reported internationally, with a significant decrease in cost an Medical Scientific Officer time.

Características de cepas chilenas de Pyrenochaeta lycopersici y perspectivas de control biológico / Characteristics of chilean Pyrenochaeta lycopersici strains and perspectives of biological control

Raíz corchosa es una de las principales enfermedades que afecta al cultivo de tomate que se produce bajo invernadero frío en Chile. En esta investigación se entregan antecedentes referentes a las principales características reproductivas de su agente causal, Pyrenochaeta lycopersici, como: picnidios, conidióforos y conidios. Ademßs, antecedentes sobre la estrategia de control biológico de esta enfermedad. En base a estudios preliminares, se determinó a Trichoderma harzianum, como el taxa mßs promisorio (según cultivos duales). Se caracterizaron cepas de ambas especies de acuerdo a crecimiento micelial a diferentes temperaturas, pH, y salinidad (NaCl). Finalmente, se efectuó un ensayo bajo condiciones controladas de invernadero, destacßndose la cepa Th11 como la mßs promisoria en el biocontrol de este patógeno.

Circulating lymphocyte subsets linked to intracellular cytokine profiles in normal humans.

To determine whether there is an association between intracellular cytokine profiles and the expression of surface antigens, we performed a simultaneous flow cytometric analysis of these laboratory parameters in 11 healthy volunteers. Peripheral blood lymphocytes were double-stained for CD4 or CD8, as well as CD11a, CD25, CD26, CD29 and CD45RA or the chemokine receptors CCR3, CCR4, CCR5 or CXCR3. Portions of the cell samples were cultured for 4 h in the presence of 1 microm monensin and 20 microg/ml brefeldin A with or without stimulation by phorbol myristate acetate plus ionomycin for the detection of intracellular interferon-gamma (IFN-gamma), interleukin-2 (IL-2), tumour necrosis factor (TNF)-alpha, and IL-4. As a result, CD4+CD29high helper inducer T cells were closely associated with IFN-gamma and TNF-alpha producing CD4+ cells, while CD4+CXCR3+ cells showed a negative correlation with IL-4-producing cells, suggesting that both of these CD4+ subsets consist mainly of Th1 cells. In contrast, CD4+CD45RA+ cells were correlated inversely with IFN-gamma and TNF-alpha-producing cells, and CD8+CD11ahigh killer effector and total CCR5+ cells showed an inverse correlation with IL-2 producing cells, suggesting an immunoregulatory role for these three subsets in non-pathological conditions. Therefore, monitoring of lymphocyte subsets that express functional surface antigens could provide additional information concerning immune deviation, as assessed by the production of Th1/Th2 type cytokines. Further, this type of combined study may provide clues for the pathogenesis of immune-mediated disorders.

Gender differences and outcome in schizophrenia: a 2-year follow-up study in a large community sample.

This study examined gender differences in the short-term (2 years) course of schizophrenia in a sample of 200 schizophrenic (DSM-IV criteria) outpatients (74 women and 126 men). Number and length of hospitalizations during the prospective follow-up were recorded. After 2 years, men were found to have more hospitalizations and longer stays than women. Among subjects who had at least one hospitalization (12 women and 38 men), men had greater length of hospitalization. In conclusion, schizophrenic women had a significantly better short-term outcome.

The Clinical Global Impression-Schizophrenia scale: a simple instrument to measure the diversity of symptoms present in schizophrenia.

OBJECTIVE: To describe the development and validation of the Clinical Global Impression-Schizophrenia (CGI-SCH) scale, designed to assess positive, negative, depressive and cognitive symptoms in schizophrenia. METHOD: The CGI-SCH scale was adapted from the CGI scale. Concurrent validity and sensitivity to change were assessed by comparison with the Positive and Negative Symptom Severity (PANSS) and Global Assessment of Functioning (GAF) scales. To evaluate inter-rater reliability, all patients were assessed by two clinicians. RESULTS: Symptoms were assessed in 114 patients. Correlation coefficients between the CGI-SCH and the GAF and PANSS scores were high (most above 0.75), and were highest for positive and negative symptoms. Reliability was substantial (intraclass correlation coefficient, ICC > 0.70) in all but one dimension (depressive dimension, ICC = 0.64). CONCLUSION: The CGI-SCH scale is a valid, reliable instrument to evaluate severity and treatment response in schizophrenia. Given its simplicity, brevity and clinical face validity, the scale is appropriate for use in observational studies and routine clinical practice.

Influence of gender on social outcome in schizophrenia.

OBJECTIVE: To study the relevance of gender on social functioning in schizophrenia. METHOD: A sample of 200 schizophrenic (DSM-IV criteria) out-patients were followed-up during 2 years and were administered the following instruments: Positive and Negative Symptom Scale (PANSS), Disability Assessment Scale (DAS-sv), and Global Assessment of Functioning (GAF) Scale. A regression model was created with DAS and GAF as dependent variables, and gender, PANSS, age of onset, duration of illness and marital status as independent variables. Separate regression models were then generated for females and males. RESULTS: Gender influenced significantly on DAS and GAF, with men showing worse functioning. In gender specific analyses, we found a significant influence of illness duration and Positive and Negative PANSS on social functioning in men, and of age at onset and Negative PANSS in women. CONCLUSION: Gender had a significant influence on social functioning in schizophrenia, even after adjusting for the other independent variables.

Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil chemotaxis.

Thioredoxin (Trx), a redox enzyme with a conserved active site (Cys-32-Gly-Pro-Cys-35), is induced and secreted into circulation in response to inflammation. Studies here demonstrate that elevating Trx levels in circulation either by i.v. injection of recombinant Trx or stimulating Trx release in Trx-transgenic mice dramatically blocks lipopolysaccharide (LPS)-stimulated neutrophil migration in the murine air pouch chemotaxis model. Furthermore, we show that leukocyte recruitment induced by the murine chemokines KC/GROalpha, RANTES (regulated upon activation, normal T cell expressed and secreted), and monocyte chemoattractant protein-1 (MCP-1) is suppressed also in Trx-transgenic mice. Addressing the mechanism responsible for this suppression, we show that circulating Trx blocks (i) the LPS-stimulated in vitro activation of neutrophil p38 mitogen-activated protein kinase, (ii) the normal down-regulation of CD62L on neutrophils migrating into the LPS-stimulated air pouch, and (iii) the in vitro adhesion of LPS-activated neutrophils on endothelial cells. However, as we also show, Trx does not alter the expression of endothelial cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, CD62P, and CD62E) within 3 h. Collectively, these findings indicate that elevated levels of circulating Trx interfere with chemotaxis by acting directly on neutrophils. We discuss these findings in the context of recent studies reporting beneficial effects of acutely elevated Trx in ischemic injury and negative effects associated with chronically elevated Trx in HIV disease.

Gender differences in a sample of schizophrenic outpatients.

Our objective was to study gender differences in schizophrenia, comparing clinical, social, and illness course characteristics. A sample of 239 schizophrenic (DSM-IV criteria) outpatients were administered the following instruments: service use and demographic questionnaires, the Positive and Negative Symptom Scale (PANSS), the Disability Assessment Scale (DAS), and the Global Assessment of Functioning (GAF) scale. The female to male ratio was 1/2. Men had an earlier age at onset. Women were more likely to be married and to live independently, and there were more unemployed men. Social functioning was slightly better in women (lower DAS scoring). No differences were found in symptomatological variables (global or separate PANSS scales), nor in type of schizophrenia. Course of illness in the past year appeared to be similar, except for longer hospital stays in men. We conclude that schizophrenic women had a significantly better social functioning, despite the lack of remarkable symptomatic differences between genders.