Molecular markers of putative spermatogonial stem cells in the domestic cat.

Spermatogonial stem cells (SSCs) are an important tool for fertility preservation and species conservation. The ability to expand SSCs by in vitro culture is a crucial premise for their use in assisted reproduction. Because SSCs represent a small proportion of the germ cells in the adult testis, culture success is aided by pre-enrichment through sorting techniques based on cell surface-specific markers. Given the importance of the domestic cat as a model for conservation of endangered wild felids, herein we sought to examine culture conditions as well as molecular markers for cat SSCs. Using a cell culture medium for mouse SSCs supplemented with glial cell-derived neurotrophic factor (GDNF), germ cells from prepuberal cat testes remained viable in culture for up to 43 days. Immunohistochemistry for promyelocytic leukaemia zinc finger (PLZF) protein on foetal, prepuberal and adult testis sections revealed a pattern of expression consistent with the labelling of undifferentiated spermatogonia. Fluorescence-activated cell sorting (FACS) with an antibody against epithelial cell adhesion molecule (EPCAM) was used to sort live cells. Then, the gene expression profile of EPCAM-sorted cells was investigated through RT-qPCR. Notably, EPCAM (+) cells expressed relatively high levels of CKIT (CD117), a surface protein typically expressed in differentiating germ cells but not SSCs. Conversely, EPCAM (-) cells expressed relatively high levels of POU domain class 5 transcription factor 1 (POU1F5 or OCT4), clearly a germ line stem cell marker. These results suggest that cat SSCs would probably be found within the population of EPCAM (-) cells. Future studies should identify additional surface markers that alone or in combination can be used to further enrich SSCs from cat germ cells.

[Analysis of the cochlear implant as a treatment technique for profound hearing loss in pre and postlocutive patients]. / Evaluación del implante coclear como técnica de tratamiento de la hipoacusia profunda en pacientes pre y post locutivos.

INTRODUCTION: These are the objectives planned for this study: 1. Evaluate the results from the communication point of view. 2. Evaluate the cochlear implant (CI) impact on the quality of life. 3. Evaluate medical complications and technical failures. 4. Assess direct and indirect costs generated during the phases of a cochlear implantation programme. 5. Determine which factors have a high impact on the clinical evolution and the financial cost. MATERIALS AND METHOD: A population of 877 patients, postlingual and prelingual, adults and children, have been studied. They were treated in 5 Spanish centres with cochlear implant programmes. Audiometric tests and global questionnaires on life quality have been carried out. Medical and CI technology complications have also been computed. Direct and indirect economic costs of a cochlear implant have been calculated. RESULTS: Postlocutive-implanted patients reached the 40 dB SPL threshold in the Pure Tone Audiometry, and this result was maintained during the 12-year evolution. In Vowels test, it evolved from a 30% on pre-stimulation to 80-90%, in Disyllables words test it evolved from a 10% to a 50-60%, and in CID Sentences test it evolved from an 18% to a 60-70%. In the prelocutive population, results were influenced by the child's age at implantation. The best results were obtained by the children who had been implanted earlier. Those implanted between 0 and 3 years old evolved in the Vowels test from 0% during pre-stimulation to 95%, from a 0% to a 90% in Disyllables words test and from a 0% to a 90-95% in CID Sentences test. Also, the speech acquisition and development of the pre-locutive population was also influenced by the implantation age. An 80% of postlocutive adult patients stated a mood and sociability improvement after the cochlear implantation. They did not show health changes in general nor relevant modifications in the attention they usually received from relatives and friends. Severe medical-surgical complications were registered for a 3.42% of the cases, a 7.06% of mild medical-surgical complications and a 3.07% of technical breakdowns in the internal components of the CI. Financial cost of implantation for a post-locutive adult oscillated between 36,912 Euro and 37,048 Euro, and between 37,689 Euro and 44,273 Euro for a pre-locutive child. CONCLUSIONS: Cochlear implants clearly enhance communication skills of the implantees. Results obtained for the prelocutive implanted population justify the creation of hearing screening programmes in new-borns. Postlocutive implanted adults have expressed satisfaction for the results obtained. However, they did perceive some limitations in situations of unfavourable acoustic conditions. An analysis of direct and indirect costs related to a CI programme has been made. It may be useful to carry out reports on the cost-benefit ratio in this field. The low index of complications observed shows which cochlear implant treatment technique complies with the adequate safety margins. The factors influencing the most in the evolution are: duration of hearing deprivation, age at implantation, cochlear anatomy and functionality of the auditory pathway, patient's and relative's motivation, and the coexistence of other handicaps associated to hearing losses.

Evaluación del implante coclear como técnica de tratamiento de la hipoacusia profunda en paciente pre y post locutivos / Análisis of the cochlear implant as a treatment technique for profound hearing loss in pre and postlocutive patients

Introducción: Los objetivos son los siguientes: 1. Evaluación de los resultados en el ámbito del lenguaje. 2. Impacto de los implantes cocleares (IC) en la calidad de vida. 3. Evaluación de las complicaciones médicas y fallos técnicos del IC. 4. Evaluación de los costes directos e indirectos generados en las diferentes fases de un programa de IC. 5. Determinar factores que repercuten en la evolución clínica y en el gasto económico. Material y Métodos: Se estudia una población de 877 pacientes con hipoacusia pre o postlocutiva, niños y adultos, tratados en 5 centros españoles con programas de IC. Se han utilizado pruebas audiométricas y cuestionarios globales de calidad de vida. Se han contabilizado las complicaciones médicas y tecnológicas de los IC. Se han calculado los costes económicos directos e indirectos de una implantación coclear. Resultados: Los pacientes postlocutivos alcanzaron umbrales de 40 dB SPL, estables a lo largo de 12 años de evolución. En Vocales pasaron de un 30% en el preoperatorio al 80-90%, en Bisílabas de un 10% a un 50-60% y en Frases CID de un 18% a un 60-70%. En la población de prelocutivos la edad de implantación influyó decisivamente en los resultados. Los mejores fueron los obtenidos en niños implantados más tempranamente. Así, aquellos implantados entre 0 y 3 años de edad en Vocales pasaron de un 0% en el preoperatorio a un 95%, en Bisílabas de un 0% a un 90% y en Frases CID de un 0% a un 90-95%. El desarrollo del lenguaje de la población prelocutiva también estuvo marcado por la edad de implantación. En torno al 80% de los pacientes adultos postlocutivos manifestaron haber mejorado su estado de ánimo y su sociabilidad. Su estado general de salud no se vio deteriorado, ni precisaron más ayudas de familiares y amigos. Se registró un 3,42% de complicaciones médico-quirúrgicas mayores, un 7,06% de complicaciones médico-quirúrgicas menores y un 3,07% de fallos técnicos en los componentes internos del IC. El costo de todo el proceso de implantación en un adulto postlocutivo osciló entre 36.912 y 37.048 euros y en niños prelocutivos entre 37.689 y 44.273 euros. Conclusiones: Los IC benefician la capacidad de comunicación de los pacientes implantados. Los resultados en la población prelocutiva justifican la puesta en marcha de programas de detección precoz de la hipoacusia infantil. Los pacientes postlocutivos adultos se muestran satisfechos con los resultados obtenidos, aunque perciben limitaciones en ambientes acústicos no favorables. Se expone un análisis de costes directos e indirectos útil para la realización de estudios coste-beneficio sobre IC en nuestro medio. El bajo índice de complicaciones indica unos márgenes de seguridad adecuados. Entre los factores que más influyen en la evolución están: la duración de la hipoacusia, la edad de implantación, la morfología coclear y la funcionalidad de la vía auditiva, la motivación del paciente y de su familia y la coexistencia de otras minusvalías asociadas a la hipoacusia

Introduction: These are the objectives planned for this study: 1. Evaluate the results from the communication point of view. 2. Evaluate the cochlear implant (CI) impact on the quality of life. 3. Evaluate medical complications and technical failures. 4. Assess direct and indirect costs generated during the phases of a cochlear implantation programme. 5. Determine which factors have a high impact on the clinical evolution and the financial cost. Materials and Method: A population of 877 patients, postlingual and prelingual, adults and children, have been studied. They were treated in 5 Spanish centres with cochlear implant programmes. Audiometric tests and global questionnaires on life quality have been carried out. Medical and CI technology complications have also been computed. Direct and indirect economic costs of a cochlear implant have been calculated. Results: Postlocutive-implanted patients reached the 40 dB SPL threshold in the Pure Tone Audiometry, and this result was maintained during the 12-year evolution. In Vowels test, it evolved from a 30% on pre-stimulation to 80-90%, in Disyllables words test it evolved from a 10% to a 50-60%, and in CID Sentences test it evolved from an 18% to a 60-70%. In the prelocutive population, results were influenced by the child’s age at implantation. The best results were obtained by the children who had been implanted earlier. Those implanted between 0 and 3 years old evolved in the Vowels test from 0% during pre-stimulation to 95%, from a 0% to a 90% in Disyllables words test and from a 0% to a 90-95% in CID Sentences test. Also, the speech acquisition and development of the pre-locutive population was also influenced by the implantation age. An 80% of postlocutive adult patients stated a mood and sociability improvement after the cochlear implantation. They did not show health changes in general nor relevant modifications in the attention they usually received from relatives and friends. Severe medical-surgical complications were registered for a 3.42% of the cases, a 7.06% of mild medical-surgical complications and a 3.07% of technical breakdowns in the internal components of the CI. Financial cost of implantation for a post-locutive adult oscillated between 36,912€ and 37,048€, and between 37,689€ and 44,273€ for a pre-locutive child. Conclusions: Cochlear implants clearly enhance communication skills of the implantees. Results obtained for the prelocutive implanted population justify the creation of hearing screening programmes in new-borns. Postlocutive implanted adults have expressed satisfaction for the results obtained. However, they did perceive some limitations in situations of unfavourable acoustic conditions. An analysis of direct and indirect costs related to a CI programme has been made. It may be useful to carry out reports on the cost-benefit ratio in this field. The low index of complications observed shows which cochlear implant treatment technique complies with the adequate safety margins. The factors influencing the most in the evolution are: duration of hearing deprivation, age at implantation, cochlear anatomy and functionality of the auditory pathway, patient’s and relative’s motivation, and the coexistence of other handicaps associated to hearing losses

Sobrecrecimiento bacteriano del intestino delagado: presentación clínica en la edad pediátrica / Bacterial overgrowth of the intestine small: clinical presentation in pediatric age

El sobrecrecimiento bacteriano es la colonización del intestino delgado por microrganismos gram-negativos y anaerobios. Las bacterias del sobrecrecimiento bacteriano del intestino delgado pueden provenir tanto de la flora bacteriana colónica como del ambiente (ingestión de agua y alimentos contaminados). En la enteropatía ambiental, por ejemplo, el SCBID es debido al aumento de la carga bacteriana ingerida. La prueba de hidrógeno en aire espirado con lactulosa se utiliza cada vez más para el diagnóstico de SCBID, sobre todo en pacientes pediátricos. Determinar la incidencia de SCBID y precisar sus formas de presentación clínica. Estudio longitudinal prospectivo realizado desde marzo de 2002 hasta noviembre de 2003. Se incluyeron los pacientes que consultaron por presentar: distensión abdominal, gases, dispepsia, diarrea crónica y dolor abdominal. El plan de estudio incluyó: historia clínica, categorización socio-económica, evaluación antropométrica, examen de heces, endoscopia digestiva superior y prueba de hidrógeno en aire espirado con lactulosa. Los pacientes con diagnóstico SCBID recibieron metronidazol por 14 días. Se incluyeron 88 pacientes (6,88±4,03 años y 63,63 por ciento femenino). La prueba de hidrógeno en aire espirado con lactulosa fue positiva en 73 pacientes (82,95 por ciento). La forma clínica de presentación de los pacientes con SCBID fue: dispepsia en 57,14 por ciento, dolor abdominal en 28,57 por ciento, dispepsia con distensión abdominal en 3,57 por ciento, dolor abdominal con distensión en 3,57 por ciento y diarrea en 7,14 por ciento. La incidencia de SCBID fue de 5.2 por cada 100 pacientes referidos. Dispepsia y dolor abdominal fueron las formas clínicas de presentación más frecuentes en la edad pediátrica.

Advantages of binaural hearing provided through bimodal stimulation via a cochlear implant and a conventional hearing aid: a 6-month comparative study.

CONCLUSIONS: Our study data demonstrate the additional benefit derived from continued use of a contralateral hearing aid (HA) post-cochlear implantation for speech recognition ability in quiet and in noise. Postoperative bimodal stimulation is recommended for all subjects who show some speech recognition ability in the contralateral ear as it may offer binaural listening advantages in various listening situations encountered in everyday life. OBJECTIVES: To assess the benefits derived from bimodal stimulation for experienced HA users implanted with a cochlear implant (CI) (score=20% in disyllabic test). The correlation between pre- and postoperative performance on speech perception measures was examined to determine additional criteria for recommending bimodal stimulation postoperatively. MATERIAL AND METHODS: A within-subject repeated-measures design was used, with each subject acting as their own control. Assessments were carried out preoperatively in aided monaural and best-aided conditions and at 6 months postoperatively in CI-alone, contralateral HA-alone and bimodal listening conditions. Speech recognition using Spanish words and sentences materials was assessed at conversational level and for soft speech in quiet. Speech comprehension in noise was assessed using word materials at a signal:noise ratio of +10, for coincident speech in noise and for spatially separated speech in noise. Twelve adult native Spanish subjects with a severe-to-profound hearing impairment who were experienced with optimally fitted conventional amplification and who displayed suboptimal speech understanding preoperatively were enrolled in the study. Preoperatively, conventional amplification was worn by five subjects binaurally and by seven monaurally. RESULTS: Postoperatively, superior speech recognition ability in quiet and in noise for disyllabic words was achieved using bimodal stimulation in comparison to performance for either monaural aided condition. Mean improvement in speech recognition in the bimodal condition was significant over performance in the CI-alone condition for disyllabic words in quiet at 70 (p=0.006) and 55 dB SPL (p=0.028), for disyllabic words in noise at +10 dB with speech and noise spatially separated with the noise source closest to the contralateral HA (S0NHA) (p=0.0005) and when the noise source was closest to the CI ear (S0NCI) (p=0.002). When testing word recognition in noise with speech and noise sources coincident in space, word scores were superior in the bimodal condition relative to the CI-alone condition but this improvement was not significant (p=0.07). The advantages of bimodal stimulation included significant effects of binaural summation in quiet and significant binaural squelch effects in both the S0NHA and S0NCI test conditions. All subjects showed superior performance in the binaural situation postoperatively relative to the best-aided condition preoperatively for one or more test situations.

[Speech understanding in post-lingual adults with cochlear implants]. / Comprensión del habla en adultos postlinguales con implante coclear.

It is well recognised that multi-channel cochlear implants are highly effective in gaining or regaining auditory perceptual skills of severe to profound hearing-impaired people. Research shows that adults rapidly improve in speech understanding after cochlear implantation. This study reports on speech understanding from two Spanish Clinics. 32 post-lingually deafened adults were fitted with either a MED-EL COMBI 40 or COMBI 40+ cochlear implant at the Hospital Universitario San Cecilio, at the Granada or Hospital Universitario La Fe, Valencia Clinic, Spain. Subjects were assessed at 1, 3, 6 and 12 months post-fitting on a number of speech perception tests. Results showed a highly significant improvement on all speech perception tests over the time. These ratify other studies in saying that cochlear implantation is a viable and successful treatment in post-lingually deafened adults.

Comprension del habla en adultos postlinguales con implante coclear / Speech understanding in post-lingual adults with cochlear implants

Es bien conocido que el implante coclear multicanal es altamente efectivo para la recuperación de las capacidades auditivas de los pacientes con hipoacusias severo-profundas bilaterales. Después de la implantación, los adultos postlinguales recuperan rápidamente la comprensión del habla. El presente estudio recoge los resultados de 32 adultos postlinguales implantados con el implante COMBI 40 y COMBI 40+ de la casa MED-EL. Los pacientes fueron evaluados al mes, tres meses, 6 meses y un año después de la implantación, mediante una serie de pruebas de percepción del habla en español. Los resultados demuestran una rápida y significativa mejoría en todas las pruebas a lo largo del tiempo de uso del implante. Estos resultados ratifican que el implante coclear es el tratamiento de elección de las hipoacusias severo-profundas bilaterales en adultos postlinguales (AU)

It is well recognised that multi-channel cochlear implants are highly effective in gaining or regaining auditory perceptual skills of severe to profound hearing-impaired people. Research shows that adults rapidly improve in speech understanding after cochlear implantation. This study reports on speech understanding from two Spanish Clinics. 32 post-lingually deafened adults were fitted with either a MED-EL COMBI 40 or COMBI 40+ cochlear implant at the Hospital Universitario San Cecilio, at the Granada or Hospital Universitario La Fe, Valencia Clinic, Spain. Subjects were assessed at 1, 3, 6 and 12 months post-fitting on a number of speech perception tests. Results showed a highly significant improvement on all speech perception tests over the time. These ratify other studies in saying that cochlear implantation is a viable and successful treatment in post-lingually deafened adults (AU)

Sensibilidad rectal en pacientes con encopresis / Sensibility rectal in patients with encopresis

Se han descrito diferencias significativas en la sensibilidad rectal de pacientes estreñidos funcionales con encopresis al compararlos con individuos normales. Hasta la fecha no existen reportes en la literatura que evalúen estas anomalias fisiológicas comparando estreñidos funcionales con y sin encopresis, por lo cual diseñamos el siguiente trabajo de investigación. Estudio transversal prospectivo en un lapso de 48 meses, de 65 pacientes con estreñimiento funcional (20 encopréticos y 45 sin encopresis), a los que se les realizó manometría anorectal con sistema capilar neumohidráulico de infusión continua de baja compliance (bomba de Armdorfer y polígrafo Sinetics). Más del 70 por ciento de los pacientes reportó un umbral de sensación rectal con un volumen de 5 mL en sendos grupos (p=0,53). El umbral de defecación en el 35 por ciento de los pacientes encopréticos es mayor de 240 mL, mientras que los no encopréticos mostraron valores superiores a 240 mL, sólo en el 2,5 por ciento de los casos(p=0,002; Odds 0,052). El 60 por ciento de los pacientes encopréticos reportaron un volumen crítico superior a 240 mL, mientras que los estreñidos funcionales sin encopresis mostraron volúmenes superiores a este valor sólo en el 28,8 por ciento de los casos (p=0,05). Los resultados sugieren que la encopresis en los pacientes con estreñimiento funcional no es secundaria a una alteración de la sensación, sino a la severidad y tiempo de evolución de la enfermedad (recto más dilatado y con mayor compliance)

Expression of p53 protein and tumor angiogenesis as prognostic factors in nasopharyngeal carcinoma patients.

The objective of this study was to evaluate the possible prognostic significance of p53 protein overexpression and tumor angiogenesis (TA) in nasopharyngeal carcinoma (NPC) patients, together with other clinicopathological variables. Forty-two NPC patients were evaluated in relation to survival. Nuclear p53 overexpression in neoplastic and endothelial cells was detected by immunohistochemistry (IHC) with the monoclonal antibody DO-7 and the polyclonal antibody against factor VIII-related antigen, respectively. Thereafter, we evaluated p53 cases in order to determine their nuclear immunoreactivity from negative (-) to positive (+, ++, +++). In addition, microvessels were counted in the most active areas of tumor neovascularization or hotspots using an image computer analyzer (MicroImage). A Cox multiple regression survival analysis was used to determine the best prognostic indicators in NPC patients. As a result, tumor microvessel count, considered as a continuous variable, was the most important independent prognostic indicator in relation to survival (p = 0.0273), with a relative risk of death of 2,4399 [95% confidence interval = 1.1051 ; 5.3871] associated with the highest microvessel counts. Moreover, the only clinicopathological variable that demonstrated prognostic value in a Cox multiple regression survival analysis was histological type (p = 0.05). In addition, we did not observe any statistical association between intratumoral microvessel density (IMD), clinicopathological variables and p53 protein expression.

Regulation of gene expression in response to oxygen in Rhizobium etli: role of FnrN in fixNOQP expression and in symbiotic nitrogen fixation.

Previously, we reported finding duplicated fixNOQP operons in Rhizobium etli CFN42. One of these duplicated operons is located in the symbiotic plasmid (fixNOQPd), while the other is located in a cryptic plasmid (fixNOQPf). Although a novel FixL-FixKf regulatory cascade participates in microaerobic expression of both fixNOQP duplicated operons, we found that a mutation in fixL eliminates fixNOQPf expression but has only a moderate effect on expression of fixNOQPd. This suggests that there are differential regulatory controls. Interestingly, only the fixNOQPd operon was essential for symbiotic nitrogen fixation (L. Girard, S. Brom, A. Dávalos, O. Lopez, M. Soberón, and D. Romero, Mol. Plant-Microbe Interact. 13:1283-1292, 2000). Searching for potential candidates responsible for the differential expression, we characterized two fnrN homologs (encoding transcriptional activators of the cyclic AMP receptor protein [CRP]-Fnr family) in R. etli CFN42. One of these genes (fnrNd) is located on the symbiotic plasmid, while the other (fnrNchr) is located on the chromosome. Analysis of the expression of the fnrN genes using transcriptional fusions with lacZ showed that the two fnrN genes are differentially regulated, since only fnrNd is expressed in microaerobic cultures of the wild-type strain while fnrNchr is negatively controlled by FixL. Mutagenesis of the two fnrN genes showed that both genes participate, in conjunction with FixL-FixKf, in the microaerobic induction of the fixNOQPd operon. Participation of these genes is also seen during the symbiotic process, in which mutations in fnrNd and fnrNchr, either singly or in combination, lead to reductions in nitrogen fixation. Therefore, R. etli employs a regulatory circuit for induction of the fixNOQPd operon that involves at least three transcriptional regulators of the CRP-Fnr family. This regulatory circuit may be important for ensuring optimal production of the cbb(3), terminal oxidase during symbiosis.

A purine-related metabolite negatively regulates fixNOQP expression in Sinorhizobium meliloti by modulation of fixK expression.

5-aminoimidazole-4-carboxamide nucleotide (AICAR) is a negative effector of cytochrome terminal oxidase cbb3 production in Rhizobium etli. In this work, the effect of AICAriboside (AICAr), the precursor of AICAR on the expression of the Sinorhizobium meliloti fixNOQP operon encoding the symbiotic terminal oxidase cbb3, was analyzed. AICAr reduced the microaerobic induction levels of fixN-lacZ and fixT-lacZ gene fusions 18- and seven-fold respectively, and both genes were activated by the transcriptional activator FixK. A fixK-lacZ fusion presented 14-fold-reduced induction levels in microaerobic cell cultures in the presence of AICAr. AICAr also reduced three-fold the microaerobic expression levels of the nifA-lacZ fusion, whose expression as well as that of fixK is controlled by the two-component system FixL-FixJ. In contrast, AICAr had no effect on the expression levels of a hemA-lacZ fusion. These data suggest that AICAr prevents fixNOQP induction by the inhibition of fixK transcription.

[Validity of hand-held systems for otoacoustic emissions in hearing screening]. / Validez de los sistemas portátiles de Otoemisiones Acústicas en el screening auditivo.

Hearing screening objective is the development of an universal screening. With that purpose, new hand-held system of Otoaccoustic Emissions have been designed, which are easier to perform and to interpret the results, to detect hearing loss disordersas soon as possible. To validate the hand-held systems of Otoaccoustic Emissions in the hearing screening, we have compared the results of the tests with Otoaccoustic Emissions clinic systems and tonal audiometry in two groups of population: new-borns and hearing-loss adults aged between 16 and 56. Our study showed that the hearing screening results in children with hand-held system were similar to classic Otoaccoustic Emissions system, but there were more than 40% of adult hearing losses not detected with this system. These results can invalidate the test.

Neurinomas acústicos medianos y grandes con audiometría tonalnormal en el momento del diagnóstico / Medium and large acoustic neurinomas with normal tonal audiometry at the time of diagnosis

Introducción. El diagnóstico precoz del neurinoma acústico es importante ante cualquier posibilidad de tratamiento, máxime dada la relación existente entre morbilidad quirúrgica y tamaño tumoral. El síntoma con que debutan más frecuentemente estos tumores es con hipoacusia perceptiva unilateral. Sin embargo, entre un 4 y un 12 por ciento se diagnostican en fases que aún no cursan con hipoacusia, incluso presentando un tamaño importante. Por ello hay que tener presentes otros síntomas que nos hagan sospechar la existencia de estos tumores y disponer de un protocolo diagnóstico que permita una detección lo más precoz posible. Pacientes y métodos. Presentamos cuatro casos de neurinoma acústico o schwannoma Mussiek et al [2] tampoco hallan relación entre el tamaño del tumor y los resultados de los PEATC. Selesnick et al [4] observan que los casos con normoacusia predominan en los tumores más pequeños pero sin grandes diferencias. Saleh et al [8] no encuentran diferencia cuando comparan el tamaño de los hipoacúsicos con los normoacúsicos. Como lo lógico es esperar que los resultados audiológicos sean proporcionales al tamaño del tumor, se han invocado diversos factores para intentar explicar las audiometrías normales incluso en tumores grandes; entre ellos estaría la consistencia del tumor, la rapidez de crecimiento (los de crecimiento más lento permitirían la adaptación del sistema nervioso), la plasticidad cerebral, etc. Sí que se ha comprobado, tanto por Musiek et al [2] como por Beck et al [6], Saleh et al [8] y los casos que presentamos, que la posibilidad de que un neurinoma curse con audición normal es más frecuente cuando el tumor afecta a personas en edad media en comparación con edades más avanzadas. Ello podría explicarse si consideramos que, al debutar en edades más tempranas, existe mayor plasticidad neural, lo que permitiría mantener el nivel auditivo gracias a una compensación central. En análisis del flujo citométrico del neurinoma acústico para estudiar la actividad biológica tumoral, valorando el ADN ploide y la fase S, Kesterson et al [5] no encuentran relación entre los síntomas iniciales, el tamaño del tumor, la edad del paciente o la duración de los síntomas con la actividad biológica del tumor. Con ello demuestran la gran variabilidad existente en el crecimiento tumoral, la precaución con que deben interpretarse los datos de los pacientes sometidos a radioterapia, y hecho de que la velocidad de crecimiento no desempeña un papel importante en las manifestaciones tumorales. Un punto discutible en los distintos artículos es lo que se considera como normoacusia, puesto que de ello depende la aproximación que efectuemos para los protocolos de detección precoz del neurinoma acústico. Habitualmente, se consideran las frecuencias 500-3.000 Hz para establecer los índices de pérdida auditiva, pero las frecuencias agudas 4.000 y 8.000 Hz pueden ser fundamentales para la detección precoz, y, si se incluyeran en los protocolos, es muy probable que el porcentaje de lo que se considera neurinomas con normoacusia variara. En resumen, existe un porcentaje de neurinomas acústicos, entre el 4 y el 12 por ciento, que se diagnostica antes de que aparezca déficit auditivo en la audiometría tonal, si bien en algunos de ellos el paciente nota déficit o distorsión auditiva. No parece existir relación entre el tamaño del tumor y la posibilidad de cursar con normoacusia. La existencia de desequilibrio, acúfenos o síntomas vestibulares unilaterales de causa desconocida requieren la práctica de PEATC para descartar un neurinoma acústico, máxime si cursan con exploración otoneurológica anormal. En la hipoacusia unilateral, en las frecuencias 4.000 y 8.000 Hz o hipoacusia bilateral asimétrica y no justificable, debe practicarse un estudio con PEATC. Los PEATC son la exploración más fiable para descartar el neurinoma acústico en la práctica otoneurológica y su anormalidad indica que debe solicitarse un estudio con resonancia magnética. El síntoma inicial más frecuente en los neurinomas que cursan con normoacusia es el desequilibrio. Los neurinomas acústicos con audición normal predominan en edades más tempranas (30-50 años), si consideramos que son tumores que aparecen hasta edades avanzadas (65-70 años). vestibular de tamaño medio y grande cuyo estudio audiológico en un principio no hacía sospechar la existencia del tumor debido a que podía considerarse una audición normal en las frecuencias conversacionales (500 a 3.000 hertzios) para la edad del paciente, o a que presentaba una curva audiométrica con hipoacusia simétrica en ambos oídos. Conclusión. Valoramos el interés diagnóstico de las pruebas practicadas y comparamos los resultados con los datos publicados en la bibliografía (AU)

Morphometric study of tumor angiogenesis as a new prognostic factor in nasopharyngeal carcinoma patients.

The aim of this study was to determine the possible prognostic significance of tumor angiogenesis (TA) in nasopharyngeal carcinoma (NPC) patients. Fifty-five NPC patients were evaluated in relation to survival. Endothelial cells were immunohistochemically stained with anti-von Willebrand factor (F-VIII), CD-31 and CD-34 antibodies, and microvessels counted in the most active areas of tumor neovascularization or hotspotsusing both a manual and an automatic method. Overall survival analysis calculated by the Kaplan Meiertest revealed that both methods were correlated with a statistical significance between intratumoral microvessel density (IMD) and overall survival, using either manual (p=0.0141) or automatic counting (p=0.0117). Other angiogenic parameters studied were perimeter, roundness and accumulative area of the microvessels using a morphometric analyzer. Moreover, our results show that cases with high IMD demonstrated a prognostic significance in relation to the accumulative area (p=0.0072).

Expression pattern of Rhizobium etli ccmIEFH genes involved in c-type cytochrome maturation.

In different bacterial species, ccmIEFH genes have been suggested to code for subunits of a bacterial haem-lyase catalyzing the covalent attachment of haem to c-type apoproteins. In Rhizobium etli CE3 there are two copies of ccmIEFH: one in the chromosome and the other located in plasmid pf. However, the null phenotype of chromosomal ccmF mutant indicates that the gene locus of plasmid pf is not functional. Two ccmI chromosomal mutants, previously isolated, produced detectable levels of c-type cytochromes under certain culture conditions in contrast with the ccmF mutant, suggesting that ccmF could be transcribed independently. The transcriptional organization of ccmIEFH operon was established. Two promoters from the chromosomal locus were mapped by primer extension, one located upstream of ccmI and the second located upstream of ccmF. The regulation of the expression of both promoters was studied using appropriate lacZ gene fusions (ccmI-lacZ and ccmEF-lacZ). The ccmI-lacZ gene fusion was expressed in complex medium, during exponential growth, under microaerobic conditions and in a R. etli mutant that accumulates reducing power, conditions where a higher respiration rate could be limited by c-type cytochrome content. The ccmEF-lacZ fusion was also primarily expressed in complex medium and under microaerophilic conditions. The finding of two independent promoters in this gene locus could suggest that the step catalyzed by CcmFH could be a rate-limiting step for c-type cytochrome assembly under certain culture conditions.

[Medium and large acoustic neurinomas with normal tonal audiometry at the moment of diagnosis]. / Neurinomas acústicos medianos y grandes con audiometría tonal normal en el momento del diagnóstico.

INTRODUCTION: Early diagnosis of an acoustic neurinoma for any possible treatment is important, especially in view of the relationship between surgical morbidity and the size of the tumour. The commonest presenting symptom of these tumors is unilateral perceptive deafness. However, between 4 and 12% are diagnosed before deafness occurs, although they may be large in size. Therefore one should remember other symptoms which lead to suspicion of these tumors, and have diagnostic guidelines available to allow the earliest possible detection. PATIENTS AND METHODS: We report four cases of acoustic neurinoma or vestibular schwannoma of medium or large size in which audiological studies did not at first give rise to suspicion of the presence of this tumour, since audition was considered to be normal at conversation frequencies (500 to 3,000 Hertz) for the age of the patient or who had an audiometry curve with symmetrical deafness in both ears. CONCLUSION: We evaluated the diagnostic importance of the tests done and compared the results with data published in the literature.