Distribución de genotipos del virus del papiloma humano en una población de mujeres españolas no vacunadas con enfermedad de vulva y vagina / The distribution of human papillomavirus genotypes within a population of non-vaccinated Spanish women with vulvar and vaginal pathology

En este estudio se han analizado un total de 86 muestras procedentes de biopsias vulvares y vaginales obtenidas en el Hospital General Universitario Gregorio Marañón de Madrid, con objeto de determinar la distribución de los genotipos del virus del papiloma humano (VPH) y el nivel de coinfección. Las muestras comprenden 61 casos de lesiones benignas vulvares (VBL), 5 lesiones intraepiteliales vulvares variedad usual (u-VIN), 2 carcinomas vulvares de células escamosas (VSCC), 9 lesiones benignas vaginales (VaBL), 4 lesiones intraepiteliales vaginales grado I (VaIN), 4 lesiones vaginales intraepiteliales grado II/III (VaIN-II/III) y un carcinoma vaginal epidermoide (VaSCC). El genotipado fue realizado con amplificación por PCR e hibridación reversa dot blot. En el total de esta serie de lesiones se detectaron 33 genotipos distintos de HPV, entre los que se incluyen 10 asociados con un alto riesgo de carcinogénesis (VPH-AR), 2 asociados con un riesgo altamente probable de carcinogénesis (VPH-PAR) y 5 asociados con un bajo riesgo de carcinogénesis (VPH-BR). En 3 muestras se detectó un VPH de genotipo indeterminado (VPH-X). Los genotipos de HPV más frecuentemente encontrados fueron el VPH-6 (10,3%; IC 95%: 6,6-15,1%), el VPH-16 (8,5%; IC 95%: 5,2-13%) y el VPH-11 (7,6%; IC 95%: 4,5-11,9%). El VPH-18 solamente fue detectado en el 0,9% (IC 95%: 0,1-3,2%) del total de virus encontrados en todas las lesiones. La coinfección por distintos genotipos del VPH se halló en el 30,2% del total de las lesiones (AU)

Vulvar and vaginal specimens were studied in order to determine the distribution of human papillomavirus (HPV) genotypes and co-infection occurrence. This information will contribute to the knowledge of HPV genotype distributions and provide an estimate of the prevalence of different oncogenic HPV genotypes found in patients in Madrid (Spain). A total of 86 vulvar and vaginal biopsies from the Hospital General Universitario Gregorio Marañón of Madrid were studied. These included 61 specimens with vulvar benign lesions (VBL), 5 usual vulvar intraepithelial lesions (u-VIN), 2 vulvar squamous cell carcinoma (VSCC), 9 vaginal benign lesions (VaBL), 4 vaginal intraepithelial lesions grade I (VaIN-I), 4 vaginal intraepithelial lesions grade II/III (VaIN-II/III) and one vaginal squamous cell carcinoma (VaSCC). HPV genotyping was performed with PCR amplification and reverse dot blot hybridization. 33 different HPV genotypes were detected, including 10 HPVs associated with a high risk of carcinogenesis, 2 HPVs associated with a highly likely risk of carcinogenesis and 5 HPVs associated with a low-risk of carcinogenesis. In 3 specimens, an uncharacteristic HPV genotype was detected. The most frequent HPV genotypes found were HPV-6 (10.3%; 95% CI: 6.6-15.1%), HPV-16 (8.5%; 95% CI: 5.2-13%) and HPV-11 (7.6%; 95% CI: 4.5-11.9%). HPV-18 was only detected in 0.9% (95% CI: 0.1-3.2%) of the total viruses detected in all lesions. HPV co-infections were found in 30.2% of all types of lesions. Benign lesions predominate in the pathology of the vulva and vagina. Although the presence of LR-HPVs is dominate among the BLV, the HR-HPVs are present in a significant number of cases (AU)

Human papillomavirus genotypes in human immunodeficiency virus-positive patients with anal pathology in Madrid, Spain.

BACKGROUND: We studied anal specimens to determine the distribution of human papillomavirus (HPV) genotypes and co-infection occurrence. This information will contribute to the knowledge of HPV genotype distributions and provide an estimate of the prevalence of different oncogenic HPV genotypes found in patients in Madrid (Spain). METHODS: We studied a total of 82 anal biopsies from the Hospital General Universitario Gregorio Marañón of Madrid. These included 4 specimens with benign lesions, 52 specimens with low-grade anal squamous intraepithelial lesion, 24 specimens with high-grade anal squamous intraepithelial lesions and 2 specimens with invasive anal carcinoma. HPV genotyping was performed with PCR amplification and reverse dot blot hybridization. RESULTS: We detected 33 different HPV genotypes, including 16 HPVs associated with a high risk of carcinogenesis, 3 HPVs associated with a highly likely risk of carcinogenesis and 14 HPVs associated with a low-risk of carcinogenesis. In two specimens, an uncharacterized HPV genotype was detected. The most frequent HPV genotypes found were HPV-16 (10.3%; 95% CI: 6.6%-15.1%), HPV-52 (8.5%; 95% CI: 5.2%-13%) and HPV-43/44 (7.6%; 95% CI: 4.5%-11.9%). HPV-18 was only detected in 0.9% (95% CI: 0.1%-3.2%) of the total viruses detected in all lesions. HPV co-infections were found in 83.9% of all types of lesions. The majority of cases (90.2%) were concomitantly infected with the human immunodeficiency virus (HIV). CONCLUSION: The prevalence of high-risk carcinogenic genotypes in anal pathological samples was remarkable. Therefore, further studies that include a greater number of samples, particularly invasive carcinoma cases are needed to evaluate the potential influence of these HPV genotypes in the appearance of anal carcinomas. Also, the influence of other accompanying infections should be evaluated clarify the appearance of this type of carcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2075238024106058.

Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain.

BACKGROUND: Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain. METHODS: A total of 533 abnormal specimens, from the Hospital General Universitario "Gregorio Marañón" of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization. RESULTS: We detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%). CONCLUSION: As our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types - such as 31, 58, 33 and 52 - in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited.

Postnatal maturation of the gastrointestinal tract: a functional and immunohistochemical study in the guinea-pig ileum at weaning.

Gastrointestinal motility is mainly controlled by the myenteric plexus. The longitudinal muscle-myenteric plexus (LMMP) preparation from the guinea-pig ileum is the best characterised adult gastrointestinal preparation; it has also been studied in old and neonatal animals, but not at weaning, when milk is substituted with the food typical of adult animals. We used LMMP preparations from weanling and adult guinea-pigs to study different functional parameters and immunohistochemically identified subpopulations of myenteric neurones, including the excitatory motor neurones to the longitudinal muscle (LM-EMN). Excitatory stimuli (low-frequency electrical stimulation, acetylcholine, substance P, and naloxone in morphine-tolerant preparations) produced similar responses in weanling and adult guinea-pigs. The endogenous cannabinoid anandamide, but not the synthetic cannabinoid agonist WIN 55,212-2 or the opioid morphine, inhibited the electrically stimulated twitches less efficaciously, and in vitro tolerance to morphine was also lower in weanling compared to adult animals. The packing densities of the calbindin-immunoreactive neurones (sensory neurones) and of neurones immunoreactive to both calretinin (CR) and neurofilament triplet protein (NFT; ascending interneurones) were slightly but significantly lower in weanling animals, whereas those of the neurones immunoreactive to CR but not NFT (LM-EMN) or immunoreactive to nitric oxide synthase (mainly inhibitory motor neurones) were comparable to the adult. Although guinea-pigs are relatively mature and can even ingest solid food at birth, their myenteric plexus is still not fully mature at the standard time of weaning. The nutritional, behavioural and environmental changes associated with weaning may be essential to attain full maturation of the myenteric plexus and gastrointestinal motility.

Genotype distribution of cervical human papillomavirus DNA in women with cervical lesions in Bioko, Equatorial Guinea.

BACKGROUND: The HVP vaccine is a useful tool for preventing cervical cancer. The purpose of this study is to determine the most frequent HPV genotypes in Equatorial Guinea in order to develop future vaccination strategies to apply in this country. METHODS: A campaign against cervical cancer was carried out in the area on a total of 1,680 women. 26 of the women, following cytological screening, were treated surgically with a loop electrosurgical excision procedure (LEEP). Cases were studied histologically and were genotyped from paraffin blocks by applying a commercial kit that recognized 35 HPV types. RESULTS: Cytological diagnoses included 17 HSIL, 1 LSIL, 5 ASC-H and 3 AGUS. Histological diagnosis resulted in 3 cases of microinvasive squamous cell carcinoma stage IA of FIGO, 9 CIN-3, 8 CIN-2, 2 CIN-1, 3 flat condylomas and mild dysplasia of the endocervical epithelium. Fifteen of twenty-five cases genotyped were positive for HPV (60%). HPV 16 and 33 were identified in four cases each, HPV 58 in two other cases, and HPV 18, 31, 52, and 82 in one case, with one HPV 16 and 58 coinfection. CONCLUSION: The frequency of HPV types in the African area varies in comparison to other regions, particularly in Europe and USA. Vaccination against the five most common HPV types (16, 33, 58, 18, and 31) should be considered in the geographic region of West Africa and specifically in Equatorial Guinea.

Losses of expression of the antigens A, Lea and Lex and over-expression of Ley in carcinomas and HG-SIL of the uterine cervix.

BACKGROUND: The glycosylation of a great number of molecules, glyco-protein or glycolipids, has been of interest for decades. OBJECTIVE: To compare the expressive patterns of the isoantigenic determinants of histo-blood groups ABH and Lewis in squamous and simple epithelium and in precursors and cancers of the cervix. METHODS: A total of 36 lesions and neoplasms (10 LG-SIL, 16 HG-SIL and 10 invasive carcinomas) have been studied with immunohistochemical techniques, using monoclonal antibodies (MoAb BG1 to BG8) for precursor chains, blood-group ABH and Lewis group Le(a), Le(b), Le(x), and Le(y), and four types of lectins. In addition, we have studied the expression of p53 protein and PCNA, establishing the rate of proliferation of each lesion. Using PCR techniques, we have also detected part of the intron of the E6 gene of HPV-16. RESULTS: In the invasive cervical carcinomas, we observed a loss of expression of the Le(x) antigen (p < 0.01). With regard to the progression of the different lesions studied, we found alterations in the patterns of expression of the antigens of the ABH and Lewis blood groups. There was a tendency towards a loss of expression and heterogeneous patterns in the more advanced lesions, as well as over-expression of the Le(y) antigens. With PCNA, we established a proliferative rate which tended to be greater in relation to the progression of the cervix neoplasms. CONCLUSION: These results indicate that there is a relation between the losses of histo-blood groups and the progression of the squamous intraepithelial lesions.

GFAP and alpha1a-AR staining and nuclear morphometry of oligodendrogliomas by confocal microscopy and image analysis: useful parameters for predicting survival in oligodendrogliomas.

OBJECTIVE: This study attempts to evaluate the GFAP and alpha1a-AR staining and morphometrical nuclear features of oligodendrogliomas and their prognostic implications as compared to present histopathology classification and their survival outcome. STUDY DESIGN: Surgical specimens from 24 patients with oligodendrogliomas during the period 1981-2000 were included. These cases were classified into two groups defined by the grade of the neoplasm: Group I: oligodendrogliomas grade II; Group II: oligodendrogliomas grade III and two groups based on the outcome status: Group of the alive cases and group of the death cases. Death rate for the groups were obtained by patients' charts. Descriptive statistics were used to examine the groups with respect to the morphometrical nuclear variables; area, perimeter, aspect, axes (major and minor), diameters (max, mean and min.), radius (max. and min.) margination, ratio of perimeter-area, roundness and sizes (length and width). In addition, an immunofluorescence method for GFAP and 1a-AR were performed and their area, density and intensity of staining were analyzed. RESULTS: Semiautomated quantitative morphometrical results showed that the variables of nuclear area (GII 48.87 microm2 vs. GIII 43.45 microm2 p-value = 0.02), aspect (GII 1.39 vs. GIII 1.55 p-value = 0.03), axis minor (GII 6.66 microm vs. GIII 6.01 microm p-value = 0.003), diameter minor (GII 5.93 microm vs. GIII 5.27 microm p-value = 0.002), radius minor (GII 2.64 microm vs. GIII 2.25 microm p-value = 0,003), perimeter-area (GII 0.0007 vs. GIII 0.0006 p-value = 0.04), size width (GII 6.60 microm vs. GIII 5.96 microm p-value = 0,003), and density of alpha1a-AR staining (GII 121.38 vs. GIII 146.03 p-value = 0.05) were statistically significant in regard of grade; and that the sum of density of GFAP (p-value = 0.01) and the intensity of alpha1a-AR (p-value = 0.01) were statistically significant in predicting survival. CONCLUSION: These results suggest that some nuclear morphometrical features and the GFAP and alpha1a-AR immunofluorescence staining may be useful parameters for predicting survival in oligodendrogliomas.

Proteomic analysis of lung biopsies: Differential protein expression profile between peritumoral and tumoral tissue.

The cellular proteome shows a dynamic profile and is subjected to changes in response to various stimuli and disease progression. Lung cancer remains the leading cause of cancer death in industrialized countries. In an attempt to find new disease markers, patients suffering from lung carcinoma have been selected to achieve differential protein expression patterns between normal and neoplasic tissue. After two-dimensional electrophoresis, the spots of interest were digested and identified by matrix-assisted laser desorption/ionization (MALDI) peptide mass fingerprinting. This information will provide a more comprehensive understanding of the disease progression and might constitute a method to complement histopathological diagnosis.

Software libre y código abiertoen aplicaciones para patología / Free software and open source in Pathology

En la actualidad la informática incide, cada vez más, en todas las áreas de la Medicina, lo cual requiere el uso creciente de sistemas y aplicaciones informáticos. En este momento, la mayoría de los programas que se utilizan son "software de licencia propietaria", lo que produce una situación de dependencia de las empresas licenciatarias. En contraposición a ello, el "software libre" pone a nuestra disposición programas que podemos utilizar sin restricciones. Esta libertad se basa, no sólo en el tipo de Licencia, sino sobre todo en que el "software libre" proporciona las fuentes, es decir, el código informático de que están hechos los programas, lo cual permite modificarlos y adaptarlos a nuestras propias necesidades. Esto significa que proporciona mayor seguridad, más estabilidad, fuerte control de calidad, herramientas más potentes, máxima compatibilidad, mejor coste/beneficio y autosuficiencia tecnológica. Además fomenta la capacidad de influencia en el desarrollo, emplea normativas estandarizadas y publicadas, por lo que, junto con su característica de universalidad e independencia de la plataforma, lo convierte en la mejor opción para la Ciencia en general y la Patología en particular (AU)

¿Es posible un estándar abierto tipo XML para las bases de datos de Patología? / Can we expect an XML-based open standard for databases in Pathology?

XML es un nuevo estándar de almacenamiento semiestructurado en el que, a diferencia del HTML, se pueden definir etiquetas o marcas personales por medio de una DTD (las Definiciones de Tipo de Documento o Restricciones de Domino) o mediante el uso de Schema. En los últimos años ha proliferado su uso como formato eficaz de almacenamiento e intercambio de datos dada su gran flexibilidad para poder representar diferentes clases de información. Para acceder a ésta información, extraerla y manipularla se han desarrollado también de forma paralela distintos lenguajes de consulta para XML como pueden ser: Xquery, Xpath, XQL, XML-QL y otros.Responsabilidad última del patólogo es la producción y gestión de informes bajo los niveles adecuados de calidad, rapidez, fiabilidad y confidencialidad en base a adecuados medios de calidad e información. Para dar respuesta acertada a éstas obligaciones pensamos que en la actualidad existen soluciones entre las que se encontraría la de desarrollar un estándar de consenso en XML que pudiera servir para interconectar distintos gestores de bases de datos de patología con el que fueran posible, al menos, intercambiar un conjunto mínimo de datos al estilo del espíritu de los proyecto SIGNO pero desde la perspectiva actual que nos dan los tiempos (AU)

Pat-UniNet: creación y desarrollo de un foro internacional, multilingüe,de diagnóstico en Patología / Pat-UniNet: Creation and development of an International Forum for Pathology Image Diagnosis

Las nuevas tecnologías de telecomunicaciones, y especialmente Internet, son nuevas oportunidades en beneficio de la Patología y los patólogos, que permiten el desarrollo y creación de foros y Comunidades Virtuales de Usuarios Patólogos integrando los diversos recursos temáticos telemáticos. Una de las actividades más relevantes es la telepatología en Internet. Este trabajo describe la creación y desarrollo del Foro Pat-UniNet de diagnóstico por imagen, al que acceden cerca de un millar de profesionales en su mayoría patólogos y su rentabilidad científica y profesional. Se revisan someramente otros recursos semejantes, y se analizan los resultados obtenidos (AU)