Investigation of EGFR/pi3k/Akt signaling pathway in seminomas.

Activation of the receptor for epidermal growth factor (EGFR) in some testicular tumors activates several signaling pathways. Some components of these pathways are phosphorylated or mutated in testicular germ tumors (TCGT), including EGFR, Kirstein ras oncogen (KRAS) and cell surface protein of the germ cell (KIT). The latter two activate RAF /MEK/ERK and PI3 K/AKT, and interconnect with the EGFR/pI3 k/Akt pathway. We investigated the expression of EGFR/pI3 k/Akt pathway proteins in seminomas and in their precursor lesion, germinal cell neoplasia in situ (GCNIS) and related genetic mutations. We used immunohistochemistry for pEGFR, pI3 k and pAkt expression with a scoring system for 46 seminoma surgical specimens: 36 classical and 10 GCNIS. In 17 samples, the mutations of EGFR (exons 19 - 21), KIT (exons 11, 17) and KRAS (exons 2, 3) were investigated using qPCR and sequencing. Of the 36 seminomas studied, 22 (61%) expressed pEGFR. Ten samples exhibited high scores for pEGFR, pI3 k and pAkt. In 5 of 17 cases (33%) some mutation was exhibited in the exons studied: 21 of EGFR (2), 17 of EGFR (1), 3 of KRAS (1) and 11 of KIT (1). Six cases exhibited nuclear translocation of EGFR; of these, four exhibited mutations of EGFR, KRAS and KIT. Eight of ten of the GCNIS expressed a high pEGFR score (80%). In 2 of 6 cases (33%), mutation was detected in exon 21 of EGFR and one smear showed EGFR translocation to the nucleus. The translocation represents a subpopulation with worse prognosis for TCGT. The EGFR/pI3 k/Akt signaling pathway is linked to TDRG1, which regulates chemosensitivity to cisplatin; this is a mechanism of resistance to treatment. TDRG1 and the EGFR/pI3 k/pAkt pathway could be therapeutic targets for seminomas resistant to cisplatin.

Association of genitourinary infections and cervical length with preterm childbirth

A prospective cohort study was conducted on a convenience sample of 1370 pregnant women with a gestational age of 20 to 25 weeks in the city of Ribeirão Preto. Data on obstetrical history, maternal age, parity, smoking habit, and a history of preterm delivery was collected with the application of a sociodemographic questionnaire. Cervical length was determined by endovaginal ultrasound, and urine and vaginal content samples were obtained to determine urinary tract infection (UTI) and bacterial vaginosis (BV), respectively. The aim of this study was to verify the association of cervical length and genitourinary infections with preterm birth (PTB). Ultrasound showed no association of UTI or BV with short cervical length. PTB rate was 9.63%. Among the women with PTB, 15 showed UTI (RR: 1.55, 95%CI: 0.93-2.58), 19 had BV (RR: 1.22, 95%CI: 0.77-1.94), and one had both UTI and BV (RR: 0.85, 95%CI: 0.13-5.62). Nineteen (14.4%) PTB occurred in women with a cervical length ≤2.5 cm (RR: 2.89, 95%CI: 1.89-4.43). Among the 75 patients with PTB stratified as spontaneous, 10 showed UTI (RR: 2.02, 95%CI: 1.05-3.86) and 14 had a diagnosis of BV (RR: 1.72, 95%CI: 0.97-3.04). A short cervical length between 20 and 25 weeks of pregnancy was associated with PTB, whereas UTI and BV determined at this age were not associated with short cervical length or with PTB, although UTI, even if asymptomatic, was related to spontaneous PTB.

Association of genitourinary infections and cervical length with preterm childbirth.

A prospective cohort study was conducted on a convenience sample of 1370 pregnant women with a gestational age of 20 to 25 weeks in the city of Ribeirão Preto. Data on obstetrical history, maternal age, parity, smoking habit, and a history of preterm delivery was collected with the application of a sociodemographic questionnaire. Cervical length was determined by endovaginal ultrasound, and urine and vaginal content samples were obtained to determine urinary tract infection (UTI) and bacterial vaginosis (BV), respectively. The aim of this study was to verify the association of cervical length and genitourinary infections with preterm birth (PTB). Ultrasound showed no association of UTI or BV with short cervical length. PTB rate was 9.63%. Among the women with PTB, 15 showed UTI (RR: 1.55, 95%CI: 0.93-2.58), 19 had BV (RR: 1.22, 95%CI: 0.77-1.94), and one had both UTI and BV (RR: 0.85, 95%CI: 0.13-5.62). Nineteen (14.4%) PTB occurred in women with a cervical length ≤2.5 cm (RR: 2.89, 95%CI: 1.89-4.43). Among the 75 patients with PTB stratified as spontaneous, 10 showed UTI (RR: 2.02, 95%CI: 1.05-3.86) and 14 had a diagnosis of BV (RR: 1.72, 95%CI: 0.97-3.04). A short cervical length between 20 and 25 weeks of pregnancy was associated with PTB, whereas UTI and BV determined at this age were not associated with short cervical length or with PTB, although UTI, even if asymptomatic, was related to spontaneous PTB.

Modulation of cathelicidins, IFNß and TNFα by bovine alpha-herpesviruses is dependent on the stage of the infectious cycle.

Production of antimicrobial peptides cathelicidins, interferons and cytokines is an important feature in airway epithelial host defense. The innate immune response to alpha-herpesvirus infection at the sites of primary replication has not been fully studied. Thus, the aim of this study was to determine the expression of innate immune components, cathelicidins, IFNß, TNFα and TNF receptors (TNFRI and TNFRII) during acute infection and reactivation of bovine herpesvirus type 1 (BoHV-1) and 5 (BoHV-5) in the respiratory tract and lymphoid tissue of their natural host. We found that BoHV infection modulates mainly the expression of BMAP28, a key cathelicidin in cattle. It was downregulated by both viruses in retropharyngeal lymph nodes of acutely infected-calves, and it was accompanied by a lower expression of IFNß, TNFα and TNFRI. BoHV-5 showed a pronounced role in the downregulation of BMAP28, even in nasal mucosa and lung. However, during reactivation, BoHV-5 upregulated both BMAP28 and IFNß in retropharyngeal lymph nodes. Acute replication induced also TNFα mRNA and protein synthesis, and expression of TNFRI and II was positively regulated during both acute infection and reactivation, particularly in the trachea. Moreover, BMAP27 was detected during BoHV-1 reactivation suggesting a potential role at this stage. Thus, cathelicidins are implicated in alpha-herpesvirus infections of the bovine respiratory system and the response is distinct during BoHV-1 and BoHV-5 acute infection and reactivation. This demonstrates that these viruses modulate differentially the components of innate immune response, possibly influencing their pathogenesis. This study provides an initial pilot analysis of factors that might be implicated in alpha-herpesvirus infection of the bovine respiratory system.

Divulgación de información sobre los pacientes del hospital: ¿Derecho o responsabilidad? / Dissemination of hospital patient data: A right or responsibility?

Los medios de comunicación son un importante actor en toda sociedad democrática. Su rol social en las cuestiones de salud, y en particular en lo relacionado con los derechos de la infancia, merece ser destacado. La manera en que se describen los niños, niñas y adolescentes en los medios tiene un impacto profundo en la actitud de la sociedad hacia la niñez. Un manejo adecuado de la imagen de la infancia que mostramos en los medios de comunicación es vital para contribuir a redimensionar la situación de los niños, niñas y adolescentes en la sociedad y valorar sus identidades, sus deseos y preferencias, sus miedos y sus derechos. Como hospital pediátrico nos cabe una gran responsabilidad respecto a lo que comunicamos, ya que los niños, niñas y adolescentes y sus familias son un grupo extremadamente vulnerable, más aún cuando son pacientes y en razón de todo ello depositan su confianza en recibir una especial protección, eminentemente asistencial y que debe ser inseparable de los aspectos jurídicos y éticos. Hay que considerar la diferencia del uso de la información con fines científicos y docentes, de la que puede ser utilizada como nota periodística, ya que van destinadas a grupos diferentes y persiguen objetivos distintos (AU)

The media is an important actor in the democratic society. Their role in health issues, particularly those related to children's rights, is outstanding. The way boys and girls and adolescents are described in the media has a profound impact on the attitude of society towards children. Adequate management of the image of childhood we show in the media is a vital contribution to the redimensioning of the situation of boys and girls, and adolescents in society respecting their identities, wishes, fears, and rights. As a pediatric hospital we have a great responsibility regarding what we communicate because boys and girls and adolescents as well as their families are an extremely vulnerable group, even more so when they are patients and consequently deposit their trust in us to receive special protection and care, which should be inseparable from judicial and ethical aspects. Data use for scientific and teaching aims should be distinguished from information used in the media, as target groups and aims pursued are different (AU)

Expressions of E2 and E7-HPV16 proteins in pre-malignant and malignant lesions of the uterine cervix.

Continuous production of the E7 protein from different types of high risk human papilloma virus (HPV) is required for progression of malignancy. We developed antibodies against HPV type 16 E7 and E2 proteins to evaluate their utility as markers for diagnosis during early stages of cervical cancer. Forty biopsies from uterine cervices were diagnosed as low grade intraepithelial lesion (LSIL), high grade intraepithelial lesion (HSIL), squamous carcinoma (SC), in situ adenocarcinoma (ISA) and invasive adenocarcinoma (AC), all of which were infected with HPV 16. Immunohistochemistry was used to investigate the expressions of E7 and E2 (both from HPV 16) and p16. P16 was expressed in eight of 12 LSILs, in all HSILs, in 16 of 18 SC and in all ACs. E2 was expressed in six of 12 LSILs. E7 was positive in eight of 12 LSILs and in all HSIL and carcinomas. The expressions of E2 and E7 of HPV16 related to p16 expression confirmed the value of the viral oncogenic proteins as complementary to histology and support the carcinogenic model of the uterine cervix, because HPVDNA integration into cellular DNA implies the destruction of the gene encoding E2, which suppresses the expression of the E6 and E7 oncoproteins. E2 from HPV16 could be marker for LSILs, while E7 could be a marker for progression of LSILs to HSILs in patients infected by HPV16, because viral typing has little positive predictive value.

Potencialidad de donación de órganos en muerte encefálica y limitación del tratamiento de soporte vital en los pacientes neurocríticos / Potential of organ donation in brain death and limitation of life support treatment in neurocritical patients

Objetivo. Analizar el perfil, la incidencia de limitaciónde tratamiento de soporte vital (LTSV) y la potencialidad de donación de órganos enpacientes neurocríticos. Diseño Multicéntrico prospectivo. Ámbito Nueve centros autorizados para extracción de órganos para trasplante...

A Short-Term Advantage for Syngamy in the Origin of Eukaryotic Sex: Effects of Cell Fusion on Cell Cycle Duration and Other Effects Related to the Duration of the Cell Cycle-Relationship between Cell Growth Curve and the Optimal Size of the Species, and Circadian Cell Cycle in Photosynthetic Unicellular Organisms.

The origin of sex is becoming a vexatious issue for Evolutionary Biology. Numerous hypotheses have been proposed, based on the genetic effects of sex, on trophic effects or on the formation of cysts and syncytia. Our approach addresses the change in cell cycle duration which would cause cell fusion. Several results are obtained through graphical and mathematical analysis and computer simulations. (1) In poor environments, cell fusion would be an advantageous strategy, as fusion between cells of different size shortens the cycle of the smaller cell (relative to the asexual cycle), and the majority of mergers would occur between cells of different sizes. (2) The easiest-to-evolve regulation of cell proliferation (sexual/asexual) would be by modifying the checkpoints of the cell cycle. (3) A regulation of this kind would have required the existence of the G2 phase, and sex could thus be the cause of the appearance of this phase. Regarding cell cycle, (4) the exponential curve is the only cell growth curve that has no effect on the optimal cell size in unicellular species; (5) the existence of a plateau with no growth at the end of the cell cycle explains the circadian cell cycle observed in unicellular algae.

Niveles de residuos peligrosos inorgánicos generados por líquidos radiográficos en efluentes de consultorios odontológicos de Asunción en el año 2012 / Levels of inorganic hazardous waste generated by liquid effluents radiographic dental offices in Asuncion in 2012

El problema de la contaminación ambiental figura entre las principales preocupaciones de la sociedad mundial debido al impacto que genera en la salud de la población y el medio ambiente en general; sin duda, los líquidos radiográficos no están ajeno a ello debido a que, los iones plata vertidos en alcantarillados sanitarios o directamente a cursos de aguas superficiales pueden producir efectos dañinos en el ambiente. Durante el proceso de revelado de las películas radiográficas se desprende un promedio del 50% de la plata que contiene la emulsión al revelar la imagen. Este metal así acumulado en el fijador remanente, si no se recupera, constituye un valioso recurso desperdiciado pues cuando llegan a la red de saneamiento se diluyen imposibilitando su recuperación. Por ello, es importante el manejo adecuado de desechos generados durante la práctica odontológica ya que por varios tiempos se ha restado importancia a los problemas ambientales. Se realizó este estudio piloto con el objetivo de evaluar los niveles de desechos peligrosos inorgánicos generados por los líquidos radiográficos provenientes de consultorios odontológicos de Asunción durante el año 2012. Con un diseño observacional descriptivo, se analizaron en laboratorio muestras de efluentes de líquidos radiográficos de 10 consultorios de Asunción, donde se determinaron concentraciones de iones plata, cromo, Demanda Química de Oxígeno y potencial de Hidrógeno, de los cuales los parámetros de plata y Demanda Química de Oxígeno sobrepasaron en gran medida los niveles máximos permitidos establecidos por la Secretaria del Ambiente. Con ello se ha constado que es necesario que los consultorios que generen cantidades de desechos de estos líquidos realicen un tratamiento previo de recuperación de la plata, y evitar, el desperdicio de este recurso mineral tan valioso a fin de evitar que sobrepase el nivel máximo permitido establecido, ya que esto genera contaminación ambiental.

Medicina complementaria o alternativa. Estudio exploratorio sobre las prácticas, creencias y actitudes de los familiares de pacientes pediátricos con enfermedades oncológicas / Complementary and alternative medicine. Exploratory study on the practices, beliefs, and attitudes of relatives of pediatric patients with oncologic diseases

La medicina alternativa o complementaria (MAC, o en inglés CAM) es una práctica con una importante presencia en nuestro medio actual. De origen milenario y presencia en todos los pueblos y culturas del mundo, su práctica persiste frente a los avances tecnológicos de la medicina alópata occidental. En nuestro país, la práctica integral de salud más convencional es la medicina alópata occidental (MAO), por lo que las otras prácticas son complementarias o alternativas, respecto de ella. Esta investigación intentó describir el contexto en el que trabajan los profesionales médicos en relación con los pacientes que practican MAC y, más específicamente, se pretendió explorar algunos aspectos de la utilización de MAC en un grupo específico de pacientes pediátricos, como es el caso de los tratados por enfermedad oncológica en el Hospital de Pediatría Dr. Juan P. Garrahan. El abordaje fue cuali y cuantitativo. Se debe considerar que el problema metodológico al abordar realidades sociales y culturales de actitudes y prácticas es especialmente complejo, ya que el objeto de estudio es de difícil aprehensión por su naturaleza y por el hecho de que la realidad estudiada es parte constitutiva de los sujetos sociales. Los datos cualitativos se obtuvieron con la realización de entrevistas semiestructuradas a los padres y/o familiares de los pacientes. Esto permitió el diseño de una encuesta para la obtención de datos cuantitativos donde se exploraron distintas variables para obtener una descripción detallada de los datos según pertenencia social, creencias religiosas, nivel educativo, lugar de origen entre otros. (AU)

Complementary and alternative medicine (CAM) is a non-conventional medical practice that has gained momentum in the modern world. With a history spanning thousands of years and healing methods that are present in different cultures, its relevance has not waned in spite of the new technological advances obtained in Western allopathic medicine (WAM). In our country, the mainstream medical practice is Western allopathic medicine, and other medical approaches become complementary or alternative in relation to the former. The aim of the present research study was to describe the context in which medical doctors work in relation to the patients that follow CAM practices, and, more specifically, to explore some aspects of CAM approaches to health care in a group of pediatric patients, such as those with oncological diseases treated at Hospital de Pediatría Dr. Juan P. Garrahan. A qualitative and quantitative analysis was performed. The methodological difficulties that are encountered when social and cultural realities of attitudes and practices are studied should be taken into account, since the object of study here is, by nature, difficult to assess and since the reality explored becomes part of the social subjects. Qualitative data were obtained by means of semistructured interviews to parents and/or family members of the patients. These interviews provided information to design a survey in order to obtain quantitative data. Several variables were analyzed in the survey, such as social class, religious beliefs and educational level, place of origin, among others. (AU)

A model for assessing habitat fragmentation caused by new infrastructures in extensive territories - evaluation of the impact of the Spanish strategic infrastructure and transport plan.

The aim of the present work is to design a model for evaluating the impact of planned infrastructures on species survival at the territorial scale by calculating a connectivity index. The method developed involves determining the effective distance of displacement between patches of the same habitat, simplifying earlier models so that there is no dependence on specific variables for each species. A case study is presented in which the model was used to assess the impact of the forthcoming roads and railways included in the Spanish Strategic Infrastructure and Transport Plan (PEIT, in its Spanish initials). This study took into account the habitats of peninsular Spain, which occupies an area of some 500,000 km(2). In this territory, the areas deemed to provide natural habitats are defined by Directive 92/43/EEC. The impact of new infrastructures on connectivity was assessed by comparing two scenarios, with and without the plan, for the major new road and railway networks. The calculation of the connectivity index (CI) requires the use of a raster methodology based on the Arc/Info geographical information system (GIS). The actual calculation was performed using a program written in Arc/Info Macro Language (AML); this program is available in FragtULs (Mancebo Quintana, 2007), a set of tools for calculating indicators of fragmentation caused by transport infrastructure (http://topografia.montes.upm.es/fragtuls.html). The indicator of connectivity proposed allows the estimation of the connectivity between all the patches of a territory, with no artificial (non-ecologically based) boundaries imposed. The model proposed appears to be a useful tool for the analysis of fragmentation caused by plans for large territories.

Experiencia del programa de trasplante de células progenitoras hematopoyéticas del Hospital de Pediatría Juan P. Garrahan / Experience of the hematopoietic stem-cell transplantation program at the Hospital Garrahan

El trasplante hematopoyético (TH) es la única o la mejor modalidad terapéutica para diversas enfermedades en Pediatría. Objetivos: Describir el programa de TH desarrollado en el Hospital de Pediatria Prof. Dr. Juan P. Garrahan y analizar prospectivamente la evolución de una cohorte de niños y adolescentes que recibieron en forma consecutiva TH en la unidad de TH. Resultados: 261 pacientes recibieron un TH alógenico y 5 pacientes un TH autólogo; 175 pacientes eran varones. La edad mediana fue de 8.2 años, (rango 0.1 -21). Las patologías más frecuentes fueron la Anemia aplástica adquirida severa (25 por ciento) y las leucemias agudas (46 por ciento). La tasa de mortalidad temprana fue 12.3 por ciento (IC95 por ciento: 8.7 -16.7 por ciento) y la tardía de 10.1 por ciento (IC95 por ciento= 6.8 - 14.3 por ciento). La probabilidad de sobrevida global fue de 62 por ciento (IC95 por ciento = 0.3971 - 0.8095) mediana (rango) de seguimiento de 45.6 meses (0.4-183.4). Las cataratas y los trastornos endocrinológicos fueron las complicaciones tardías más frecuentes. Los sobrevivientes presentaron una buena capacidad funcional y calidad de vida. Conclusiones. La selección de los pacientes y donantes, el desarrollo de la infraestructura de apoyo para la preparación de pacientes y donantes, y la capacitación del personal involucrado directa o indirectamente ha permitido alcanzar resultados de mortalidad relacionada al trasplante, sobrevida y calidad de vida comparables a los publicados por centros con vasta experiencia en pacientes pediátricos.

Contribución de la vigilancia del crecimiento a la calidad de atención: un modelo de gestión / Contribution to the monitoring of growth and quality of patient care: a management model

El estudio del crecimiento a largo plazo de niños con raquitismo hipofosfatémico familiar, demostró que 18 de los 30 pacientes estudiados no crecían adecuadamente, y que a su vez este pobre crecimiento estaba asociado a una falta de cumplimiento de la ingesta de fósforo indicada por el médico tratante, medicación que forma parte esencial de la terapia. Entre las principales causas identificadas de falta de cumplimiento se encontró la incapacidad de muchas farmacias del país de preparar la solución de sales de fósforo, las dificultades de transporte y conservación de dichas sales, la inestabilidad de la solución, la falta de recursos de los pacientes sin cobertura, la dificultad de las obras sociales en financiar las sales en los pacientes con cobertura. Luego de reuniones mantenidas entre miembros de un equipo multidiciplinarios formado ad hoc, la farmacia del hospital logró preparar una cápsula con sales de fósforo para ser disuelta en agua en el hogar, se estableció un circuito de entrega gratuita del medicamento al paciente aprobado por las autoridades del Hospital, y un sistema de cobro a los organismos pagadores en los casos que correspondiera. La autorización de la Dirección fue tomada en base a la necesidad de mejorar la calidad de atención en estos pacientes, al relativo bajo costo del medicamento (1180 pesos por pacientes por año), y el escaso número de pacientes bajo tratamiento. La vigilancia del crecimiento en pacientes crónicos probó en este caso ser una herramienta confiable y sencilla para detectar un problema generalizado en el tratamiento de una enfermedad y mejorar la calidad de la atención.

[Music versus diazepam to reduce preoperative anxiety: a randomized controlled clinical trial]. / Estudio comparativo de la eficacia de la música frente al diazepam para disminuir la ansiedad prequirúirgica: un ensayo clínico controlado y aleatorizado.

OBJECTIVES: To compare the effectiveness of music to that of diazepam in reducing preoperative anxiety. PATIENTS AND METHODS: Patients were randomized to 2 groups to receive diazepam or listen to music on the day of surgery and the previous day. Just before the operation, anxiety was assessed with the State-Trait Anxiety Inventory. Cortisol levels, heart rate, and blood pressure were also recorded. RESULTS: Two hundred seven patients were enrolled. No significant differences in any of the outcome measures (anxiety, cortisol level, heart rate, or blood pressure) were found between the 2 groups (music vs sedative). CONCLUSIONS: Our findings indicate that music is as effective as sedatives for reducing preoperative anxiety.

Antiretroviral agents and acid-base balance at delivery of the neonate

Limited evidence is available regarding antiretroviral (ARV) safety for uninfected infants exposed to these drugs in utero. Our objective was to determine if ARV administered to pregnant women is associated with decreasing umbilical arterial pH and base excess in uninfected infants. A prospective study was conducted on 57 neonates divided into three groups: ZDV group, born to mothers taking zidovudine (N = 20), triple therapy (TT) group, born to mothers taking zidovudine + lamivudine + nelfinavir (N = 25), and control group (N = 12), born to uninfected mothers. Umbilical cord blood was used to determine umbilical artery gases. A test was performed to calculate the sample by comparing means by the unpaired one-tailed t-test, with a = 0.05 and ß = 20 percent, indicating the need for a sample of 18 newborn infants for the study groups to detect differences higher than 20 percent. The control and ARV groups were similar in gestational age, birth weight, and Apgar scores. Values of pH, pCO2, bicarbonate, and base excess in cord arterial blood obtained at delivery from the newborns exposed to TT were 7.23, 43.2 mmHg, 19.5 mEq/L, and -8.5 nmol/L, respectively, with no significant difference compared to the control and ZDV groups. We conclude that intrauterine exposure to ARV is not associated with a pathological decrease in umbilical arterial pH or base excess. While our data are reassuring, follow-up is still limited and needs to be continued into adulthood because of the possible potential for adverse effects of triple antiretroviral agents.

Association of tumor necrosis factor a-2 and a-8 microsatellite alleles with human papillomavirus and squamous intraepithelial lesions among women in Brazil.

Infection with oncogenic human papillomavirus (HPV) is considered to be the major risk factor for cervical cancer. Tumor necrosis factor (TNF) is a pluripotent cytokine that plays an important role in inhibiting the action of microbial agents, and TNF microsatellite polymorphisms have been associated with several diseases, including cancer and viral infections. This study analyzed the associations between TNFa to -e microsatellite polymorphisms and the severity of squamous intraepithelial lesions (SIL), according to the presence of the oncogenic HPV16 and HPV18 types. Samples from 146 HPV-positive women with low-grade SIL (LSIL) and high-grade SIL (HSIL) and samples from 101 healthy women were studied. TNF microsatellite polymorphism typing and HPV detection and typing were performed using PCR-amplified DNA hybridized with sequence-specific primers. Data were analyzed by Fisher's exact test using the GENEPOP software. Significant associations were observed between LSIL and the TNFa-8 allele (4/166; P = 0.04), as well as between TNFa-2 with HPV18 only (16/44; P = 0.002) and TNFa-2 with HPV18 coinfection with HPV16 (16/44; P = 0.001). Patients exhibiting the TNFa-2 allele and harboring HPV18, in the presence or absence of coinfection with HPV16, had an increased risk of HSIL occurrence (13/38; P = 0.04; 5/10; P = 0.04) compared to patients with other HPV types. These results suggest that the TNFa-8 allele is associated with increased susceptibility to the occurrence of LSIL and that despite the presence of a high TNF-alpha production allele, the ability of HPV18 to resist the inhibitory effects of TNF-alpha may contribute to the occurrence of infection and consequently to HSIL in women with cervical HPV18 infection.