Desarrollo de lenguaje en niños con implante coclear en centro terciario de salud: serie clínica / Language development in children with cochlear implant at a tertiary health care center: clinical series

Resumen Introducción: Desde la década de los 90, los implantes cocleares han progresado desde aplicaciones experimentales a un uso clínico estandarizado en niños con pérdida auditiva severa y profunda. Las investigaciones han producido cambios en la tecnología de los implantes y ha dado lugar a la expansión de los candidatos a implante para incluir a los niños menores de 2 años de edad. El objetivo principal de la implantación coclear pediátrica es facilitar el desarrollo del lenguaje hablado. A pesar de los avances en la tecnología de implantes y los cambios en el manejo de la pérdida auditiva, los resultados de lenguaje en niños son todavía muy variables, participando de este proceso tanto el tratamiento oportuno, la red familiar y nivel socioeconómico entre algunos de ellos. Objetivo: Describir resultados de niños menores 6 años sometidos a cirugía de implante coclear en un centro terciario de salud. Material y método: Estudio longitudinal de cohorte retrospectivo, análisis a 99 pacientes implantados en centro terciario de salud desde inicio programa en 1994 a 2015. Resultados: 99 pacientes, 57% hombres 43% mujeres, edad promedio implantación 16,3 meses. 54,8% casos origen congénito no especificado o prematurez. En 74,4% se objetivó presencia de lenguaje auditivo verbal. El nivel socioeconómico (NSE) mostró asociación con no desarrollo de lenguaje (p =0,009) evidenciando que pacientes de bajo NSE 20% no desarrolla lenguaje. La variable discapacidad asociada (p <0,001) y la variable NSE (p =0,036) se asociaron de manera independiente a lenguaje de señas o no desarrollo de lenguaje oral. Conclusión: Los implantes cocleares ofrecen una opción en la rehabilitación auditiva en hipoacusia sensorio neural profunda, para candidatos de todo el espectro de edad, sin embargo los resultados dependen en gran medida del entorno en el que se utilizan los implantes cocleares.

ABSTRACT Introduction: Since the 90s, cochlear implantation has progressed from experimental to standard clinical practice for children with severe and profound hearing loss. Research has produced changes in implant technology and has led to the expansion of implant candidacy to include children younger than 2 years of age. The primary goal of pediatric cochlear implantation is to facilitate spoken language development. Despite the advances in implant technology and the changes to the management of hearing loss, language outcomes for children are still highly variable, participating in this process both timely treatment, the family network and socio economic level among others. Aim: describe outcomes of patients younger than 6 years undergoing cochlear implant surgery in a tertiary care center. Material and method: retrospective longitudinal cohort study, 99 patients implanted in a tertiary health center since the program's inception in 1994 to 2015 was analyzed. Results: 99 patients, 57 % men 43 % women, average age of implantation 16.3 months. 54.8 % of cases were congenital or prematurity. In 74.4 % they had auditory verbal language. Socioeconomic status (SES) showed association with the lack of language development (p =0.009) demonstrating that low SES patients (20%) do not develop language. The disability associated variable (p <0.001) and the SES variable (p =0.036) were independently associated with sign language or no oral language development. Conclusions: Cochlear implants offer an option for hearing rehabilitation in profound hearing loss, for candidates of all ages, however the results depend largely on the environment in which cochlear implants are used.

Resultados del programa de implantes cocleares de Clínica Las Condes a 20 años de su inicio: serie clínica 1994-2015 / Cochlear implant program results in Clinica Las Condes 20 years since the beginning: clinical series 1994-2015

RESUMEN Introducción: La hipoacusia sensorioneural es la tercera causa de discapacidad en Chile, con incidencia en recién nacidos de 1 a 3 casos cada 1.000 recién nacidos vivos, y prevalencia en adultos de hasta 70%, siendo muchos casos susceptibles de ser tratados mediante implante coclear. Objetivo: Describir resultados de los pacientes sometidos a cirugía de implante coclear en Clínica Las Condes (CLC). Material y método: Estudio longitudinal de cohorte retrospectiva, se analizaron a 237 pacientes implantados en Clínica Las Condes desde 1994 al año 2015. Resultados: Se analizan 237 pacientes, 106 mujeres (44,7%) y 131 hombres (55,3%). El 65,5% de los pacientes se implantaron entre los 2-6 años de vida. Las etiologías más frecuentes fueron hipoacusia congénita no sindrómica (45,9%), genética tardía (11,8%) y posmeningitis (11,4%). Se encontró asociación significativa entre promedio tonal de la palabra (PTP) y presencia de malformación coclear (p =0,008). Sólo 9,9% de los pacientes presentaron otra discapacidad asociada a la hipoacusia. La tasa de reimplante fue 16,3% y sólo la variable malformación coclear se asoció a ella (p =0,016). Conclusión: El implante coclear es una herramienta beneficiosa en pacientes hipoacúsicos que no se benefician de otros dispositivos auditivos ofreciendo la posibilidad de reinsertarlos social y laboralmente con bajo riesgo quirúrgico y alta tasa de éxito.

ABSTRACT Introduction: Sensorineural hearing loss is the third leading cause of disability in Chile, with incidence in infants 1 to 3 cases per 1,000 newborn and prevalence in adult up to 70%, with many cases that can be treated with cochlear implant. Aim: to describe outcomes of our series of patients undergoing cochlear implant surgery at Clinica Las Condes (CLC). Material and method: Retrospective longitudinal cohort study, 237 patients implanted in our center since 1994 to 2015 were analyzed. Results: 237 patients, 106 women (44.7%) and 131 men (55.3%) received a cochlear implant during this period. 65.5% of patients were implanted between 2-6 years of age. The most common etiologies were; non-syndromic congenital deafness (45.9%), late genetic onset (11.8%) and meningitis (11.4%). A significant association between the average pure tone average and presence of cochlear malformation (p =0.008) was demonstrated. Only 9.9% of patients had other disabilities associated with hearing loss. Re-implantation rate was 16.3% and only the variable cochlear malformation was associated to it (p =0.016) Conclusions: The cochlear implant provides clear benefits to patients with hearing impairment who do not benefit from other hearing devices offering the possibility of social and labor reintegrating, with low surgical risk and high success rate.

Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy.

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.

Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy.

A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs.

Skeletal injuries sustained during the Haiti earthquake of 2010: a radiographic analysis of the casualties admitted to the Israel Defense Forces field hospital.

PURPOSE: To report the distribution and types of skeletal injuries demonstrated on the images taken at the field hospital following the Haiti 2010 earthquake. METHODS: Following the January 12, 2010, earthquake, the State of Israel dispatched a field hospital to Haiti, managing 1,111 patients from January 17, 2010, to January 26, 2010. Four hundred and seven patients (37 %) had 684 radiographic images, most of them (87 %) due to presumed skeletal injuries. RESULTS: There were 224 limb fractures (excluding the hands and feet), with 77 % of them in the lower limbs (30 % femur, 17 % tibial shaft, 16 % ankle). Out of 37 axial skeleton fractures, 30 involved the pelvis (21 anterior posterior, three vertical shear, three lateral compression, three combined). Nine traumatic dislocations (five hips, three shoulders, one knee) were reduced. After reviewing all the digital radiographs, on a PACS-compatible radiography screen, few false diagnoses (2 %) were encountered, with none of them affecting the management of these injuries. CONCLUSIONS: To the best of our knowledge, this is the first report of the radiological results emerging from a field hospital following a mass casualty event. Laptop personal computer-based workstations provide an adequate solution for radiographic image viewing in a field hospital setting. Recognition of the prevalence and distribution of skeletal injuries can improve the preparedness of such delegations before departure in the future.

Habitat use by Collared Crescentchest (Melanopareia torquata) in a Cerrado in southeastern Brazil: implications for management / Uso de habitat pelo tapaculo-de-colarinho (Melanopareia torquata) em um Cerrado do sudeste do Brasil: implicações para o manejo

The Collared Crescentchest (Melanopareia torquata) is a small insectivore endemic to the Cerrado. We examine the habitat use of this bird in a preserved Cerrado area in southeastern Brazil. Despite its occurrence in grassland with shrubs, the species used these areas less frequently than expected. The Collared Crescentchest mainly used areas of campo cerrado, but it was not recorded in a disturbed one. The common occurrence of exotic grass (U. decumbens) and cattle grazing may have brought about factors for its occurrence. However, the preference for native grasses may indicate an adverse indirect relationship against its occurence as there is competition between native and exotic grasses in the Cerrado. The presence of the Collared Crescentchest included the highest density of tall shrubs (>1 m) and native grasses. Conservation of the species should involve preserved areas of campo cerrado with a dominance of native grasses and tall shrubs.

O tapaculo-de-colarinho (Melanopareia torquata) é uma pequena ave insetívora e endêmica do Cerrado. Examinou-se o uso do habitat dessa ave em uma área de Cerrado preservado no sudeste do Brasil. Apesar de a espécie ser registrada em áreas campestres com arbustos, a sua ocorrência foi menos frequente do que o esperado. O tapaculo-de-colarinho utilizou principalmente áreas de campo cerrado, entretanto não foi registrado em áreas alteradas de campo cerrado. A ocorrência comum de gramíneas exóticas (U. decumbens) e o seu consumo frequente durante o pastoreio do gado podem ter sido fatores agravantes para a ausência da ave nessa área. Contudo, a presença de gramíneas exóticas não inibiu o registro da espécie. O tapaculo-de-colarinho está associado a microhabitat com maior densidade de arbustos altos (>1 m) e gramíneas nativas. Apesar de as gramíneas exóticas não inibirem a presença da espécie, a preferência por gramíneas nativas pode indicar uma relação adversa indireta em razão da competição entre espécies nativas e exóticas do Cerrado. A conservação da espécie envolve a preservação de áreas de campo cerrado com dominância de gramíneas nativas e arbustos altos.

Habitat use by Collared Crescentchest (Melanopareia torquata) in a Cerrado in southeastern Brazil: implications for management.

The Collared Crescentchest (Melanopareia torquata) is a small insectivore endemic to the Cerrado. We examine the habitat use of this bird in a preserved Cerrado area in southeastern Brazil. Despite its occurrence in grassland with shrubs, the species used these areas less frequently than expected. The Collared Crescentchest mainly used areas of campo cerrado, but it was not recorded in a disturbed one. The common occurrence of exotic grass (U. decumbens) and cattle grazing may have brought about factors for its occurrence. However, the preference for native grasses may indicate an adverse indirect relationship against its occurence as there is competition between native and exotic grasses in the Cerrado. The presence of the Collared Crescentchest included the highest density of tall shrubs (>1 m) and native grasses. Conservation of the species should involve preserved areas of campo cerrado with a dominance of native grasses and tall shrubs.

Habitat use by Collared Crescentchest (Melanopareia torquata) in a Cerrado in southeastern Brazil: implications for management

The Collared Crescentchest (Melanopareia torquata) is a small insectivore endemic to the Cerrado. We examine the habitat use of this bird in a preserved Cerrado area in southeastern Brazil. Despite its occurrence in grassland with shrubs, the species used these areas less frequently than expected. The Collared Crescentchest mainly used areas of campo cerrado, but it was not recorded in a disturbed one. The common occurrence of exotic grass (U. decumbens) and cattle grazing may have brought about factors for its occurrence. However, the preference for native grasses may indicate an adverse indirect relationship against its occurence as there is competition between native and exotic grasses in the Cerrado. The presence of the Collared Crescentchest included the highest density of tall shrubs (>1 m) and native grasses. Conservation of the species should involve preserved areas of campo cerrado with a dominance of native grasses and tall shrubs.

O tapaculo-de-colarinho (Melanopareia torquata) é uma pequena ave insetívora e endêmica do Cerrado. Examinou-se o uso do habitat dessa ave em uma área de Cerrado preservado no sudeste do Brasil. Apesar de a espécie ser registrada em áreas campestres com arbustos, a sua ocorrência foi menos frequente do que o esperado. O tapaculo-de-colarinho utilizou principalmente áreas de campo cerrado, entretanto não foi registrado em áreas alteradas de campo cerrado. A ocorrência comum de gramíneas exóticas (U. decumbens) e o seu consumo frequente durante o pastoreio do gado podem ter sido fatores agravantes para a ausência da ave nessa área. Contudo, a presença de gramíneas exóticas não inibiu o registro da espécie. O tapaculo-de-colarinho está associado a microhabitat com maior densidade de arbustos altos (>1 m) e gramíneas nativas. Apesar de as gramíneas exóticas não inibirem a presença da espécie, a preferência por gramíneas nativas pode indicar uma relação adversa indireta em razão da competição entre espécies nativas e exóticas do Cerrado. A conservação da espécie envolve a preservação de áreas de campo cerrado com dominância de gramíneas nativas e arbustos altos.

Frecuencia de agentes virales en niños con afectación del sistema nervioso central en el estado Zulia, Venezuela: durante el año 2007 / Incidence of viral agents in children with central nervous system affectation in the state of Zulia, Venezuela: during 2007

Diversos virus afectan el sistema nervioso central (SNC) ocasionando encefalitis, principalmente en la edad pediátrica. Determinar la implicación de agentes virales en infecciones del sistema nervioso central (SNC) en niños del estado Zulia, Venezuela durante el año 2007. Se recolectaron 109 muestras de líquido cefalorraquídeo(LCR) y suero, provenientes de pacientes entre 1 día de nacido a 14 años, que presentaron sintomatología clínica sugestiva de afectación del SNC y cuyo estudio bacteriológico convencional de LCR resultó negativo. Se determinó la relación albúmina LCR/suero a fin de descartar contaminación, resultando 24 pares óptimos para la determinación por la técnica de ELISA de anticuerpos IgM específicos para los virus Herpes Simple (VHS), Epstein Barr (VEB), Dengue, Rubéola, Sarampión y Encefalitis Equina Venezolana (EEV). De los 24 casos analizados, 15 (62,5%) resultaron positivos. Los agentes causantes de encefalitis fueron: 11 casos de Dengue (45,8%) (p<0,05), 3 de VHS (12,5%) y un caso de VEB (4,2%). No se detectaron casos de Rubéola, Sarampión, ni EEV. La pleocitocis con predominio de linfocitos fue el hallazgo más frecuente en los casos con encefalitis viral (EV) confirmada, sin diferencias significativas al relacionarlo con el agente viral infectante. Se evidencia que una proporción significativa de los niños con encefalitis es debida a agentes virales y se destaca un incremento en los casos de dengue con afectación del SNC en la región

Various viruses affect the central nervous system (CNS) causing encephalitis, mainly in pediatric patients. To determine the involvement of viral agents for central nervous system (CNS) infections in children in the State of Zulia, Venezuela during the year 2007. 109 samples of cerebrospinal fluid (CSF) and serum were collected from patients between 1 day and 14 years of age, who presented clinical symptoms suggestive of CNS involvement and whose conventional CSF bacteriological study proved negative. The CSF Albumin /serum relation ship was determined in order to rule out contamination, resulting in 24 optimal pairs for determining the IgM and IgG antibodies specific for herpes simplex virus (HSV), Epstein Barr (EBV), Dengue fever, rubella, measles and Venezuelan Equine Encephalitis (VEE) using the ELISA technique. Of the 24 cases examined, 15 (62.5%) were positive. The causative agents for encephalitis were 11 cases of Dengue (45.8%) (p<0.05), 3 VHS (12.5%) and 1 case of EBV (4.2%). There were no cases of rubella, measles or VEE. Pleocytosis with lymphocyte predominance was the most common finding in cases with confirmed viral encephalitis (VE), without significant differences related to the infecting viral agent. Results show that a significant proportion of encephalitis in children is due to viral agents, highlighting an increase in dengue cases with CNS affection in the region

Evaluación de la inmunidad a los virus de sarampión y varicela en niños y adolescentes del Municipio Páez del Estado Zulia, Venezuela / Evaluation of immunity to measles and varicella (chickenpox) viruses in children and adolescents of the Páez Municipality, State of Zulia, Venezuela

Las enfermedades exantemáticas son un grupo de patologías causadas por agentes virales, que se presentan frecuentemente sobre todo durante los primeros años de vida y responden en su mayor proporción a infecciones causadas por virus como sarampión, varicela, rubéola y dengue, entre otros. El objetivo de este estudio fue evaluar la inmunidad a los virus de sarampión y varicela en niños y adolescentes, residentes del municipio Páez del estado Zulia, Venezuela. Se estudiaron 174 muestras provenientes de escolares y adolescentes aparentemente sanos, sin distingo de sexo y en un rango de edad comprendido entre 8 a 17 años, las cuales fueron analizadas mediante la técnica de ELISA. Se detectó una frecuencia de 59,7 por ciento para el virus del sarampión y un 44,8 por ciento para varicela. La seroprevalencia para sarampión y varicela estuvo homogéneamente distribuida en todos los grupos etarios. En ambas enfermedades se observó una mayor frecuencia en el sexo masculino, no encontrándose diferencias significativas. Se evidencia una baja inmunidad a estos virus, se sugiere incrementar los programas de vacunación en este municipio para eliminar la circulación de estos agentes infecciosos en la población

Exanthematic diseases are a group of pathologies caused by viral agents, which appear frequently during the first years of life and respond in greater proportion to infections caused by viruses, such as measles, varicella (chickenpox), rubella (German measles) and dengue, among others. The objective of this study is to evaluate immunity to measles and chickenpox viruses in children and adolescents residing in the Páez municipality, state of Zulia, Venezuela. Without regard to sex, 174 samples from apparently healthy adolescents and children between 8 and 17 years old were studied and analyzed using the ELISA technique. A frequency of 59.7 percent was detected for the measles virus and 44.8 percent for varicella. Seroprevalence for measles and varicella was distributed homogeneously in all age groups. For both diseases, greater frequency was observed in males, without significant differences. The study demonstrated low immunity to these viruses and suggests increasing vaccination programs in this municipality to eliminate circulation of these infectious agents in the population

Relationship between the characteristics of hospitalised acute asthma patients and the severity of their asthma. A case-control study.

BACKGROUND: The EAGLE project database was analysed to assess the characteristics of patients with severe (SA) who required hospitalisation as a result of an acute episode during the period 1994-2004, and the relationship with asthma severity. METHODS: A total od 2593 clinical records corresponding to an equal number of patients hospitalised for acute asthma (15-69 years), with sufficient information to characterize their asthma severity in agreement with GNA criteria were identified (727 patients with SA compared with 1866 patients with non-severe asthma). RESULTS: Patients with SA were older, displayed a greater predominance of female asthmatics, lower antecedents of atopy, and a higher frequency of previous hospitalisations compared with non-severe asthmatics (86.1% vs. 50.5%, p< or = 0.01). Additionally, SA patients showed more severe exacerbations characterized by acidosis, significant spirometric deterioration, greater length of hospital stay (9.4 days vs. 7.0 days), as well as a higher frequency of intubation (16.8% vs. 2.1%), intensive care unit admission (11.3% vs.4.9%), cardiopulmonary arrest (5.5% vs. 1.3%), and asthma deaths (2.1% vs. 0.4%) (all < or = 0.01) compared wit non-severe patients. CONCLUSIONS: This study suggests that SA patients have greater morbidity and a disproportionate need for health care as a result of more severe exacerbations. However, non-severe asthmatics can also still present acute severe episodes (although with a lower frequency) with risk of life.

Evaluación retrospectiva de fiebre amarilla selvática en Venezuela período 2003-2005 / Retrospective evaluation of jungle yellow fever in Venezuela during the years 2003-2005

La fiebre amarilla es una enfermedad viral, propia de algunas regiones tropicales de América del Sur y Africa, causando numerosas epidemias con elevadas tasas de mortalidad. Con el objetivo de caracterizar retrospectivamente el brote de fiebre amarilla selvática en Venezuela en el año 2003, a través de la determinación del número de casos confirmados y defunciones en los estados afectados, según grupos etarios, sexo, ocupación y procedencia y la identificación de factores desencadenantes del brote, así como también el estudio de los casos reportados en los años 2004 y 2005, se estudiaron los casos registrados oficialmente en el estado Zulia, durante el periodo de estudio. El Zulia fue el estado más afectado en el período evaluado con 25 casos (p<0,001), reportando mayor tasa de ataque durante el año 2003, Mérida y Monagas en el año 2004, y Portuguesa en el 2005. El grupo etario más afectado fue 25-44 años, predominando el sexo masculino, afectando mayormente al trabajador agrícola. Los resultados evidencian la alta letalidad de la fiebre amarilla al arrojar un 46,51 por ciento en el año 2003, 60 por ciento en el 2004 y 66,67 por ciento en el 2005. Se recomienda la implementación de medidas que permitan establecer una vigilancia mínima en las zonas con actividad demostradas.

Yellow fever is a viral disease, typical of some tropical regions in South America and Africa, causing numerous epidemics with high mortality rates. In order to characterize retrospectively the jungle yellow fever outbreak in Venezuela in the year 2003, by determining the number of cases and deaths confirmed in the affected states according to age, sex, occupation and origin and by identifying factors that triggered the outbreak, as well as the study of cases reported in 2004 and 2005, cases officially registered in the State of Zulia were studied for the period in question. Zulia was the state most affected during the period evaluated, with 25 cases (p <0.001), reporting the highest attack rate during 2003; Merida and Monagas had the highest rates in 2004, Portuguesa in 2005. The most affected age group was 25-44 years, predominantly male farm workers. Results showed the high lethality of yellow fever: 46.51 percent in 2003, 60 percent in 2004 and 66.67 percent in 2005. The implementation of measures to establish a minimum surveillance in areas with proven activity is recommended.

Anti-beta1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease.

Chronic Chagas heart disease (cChHD), a chronic manifestation of the Trypanosoma cruzi infection, is characterized by high antibody levels against the C-terminal region of the ribosomal P proteins (i.e. peptide R13, EEEDDDMGFGLFD) which bears similarity with the second extracellular loop of beta1-adrenergic receptor (beta1-AR, peptide H26R HWWRAESDEARRCYNDPKCCDFVTNR). Because it has not been demonstrated clearly that IgGs from cChHD patients bind to native human beta1-AR, the aim of this study was to investigate further the physical interaction between cChHD IgGs and the human beta1-AR. Immunofluorescence assays demonstrated the binding of these antibodies to the receptor expressed on stably transfected cells, together with a beta1-AR agonist-like effect. In addition, immunoadsorption of the serum samples from cChHD patients with a commercially available matrix, containing peptides representing the first and the second extracellular loop of the beta1-AR, completely abolished reactivity against the H26R peptide and the physiological response to the receptor. The follow-up of this specificity after in vitro immunoadsorption procedures suggests that this treatment might be used to diminish significantly the serum levels of anti-beta1-AR antibodies in patients with Chagas heart disease.

Long-term outcomes in liver transplant patients with hepatic C infection receiving tacrolimus or cyclosporine.

Choice of calcineurin inhibitor may be a contributing factor to deteriorating patient and graft survival following liver transplantation for hepatitis C virus (HCV). In our multicenter, open-label LIS2T study, de novo liver transplant patients stratified by HCV status were randomized to cyclosporine or tacrolimus. Follow-up data were obtained in an observational study of 95 patients. Mean follow-up was 34 and 37 months, respectively, for cyclosporine-treated (n = 47) and tacrolimus-treated (n = 48) patients. In patients not receiving antiviral therapy, 22 of 31 given cyclosporine (72%) and 24 of 29 given tacrolimus (83%) had biochemical recurrence of HCV. In 68 patients with at least one biopsy, histological evidence of HCV-related hepatitis was present in 27 of 31 (87%) cyclosporine-treated patients and 37 of 37 (100%) tacrolimus-treated patients (P = .02, chi-square test). Three-year actuarial risk of fibrosis stage 2 was 66% with cyclosporine and 90% with tacrolimus; for fibrosis stage 3 or 4 it was 46% and 80%, respectively. Three graft losses were attributed to HCV recurrence in cyclosporine-treated patients and six in tacrolimus-treated patients. Tacrolimus may be associated with increased risk of histological HCV disease recurrence compared to cyclosporine.

Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor.

Antibodies from patients with Chagas heart disease and monoclonal antibodies (or mAb) to the carboxy-terminal end (B cell epitope R13) of the ribosomal P2beta protein of Trypanosoma cruzi (TcP2beta) cross-react with the beta1 adrenergic receptor (beta1-AR). Two single-chain Fv fragments (scFv) C5 and B7 derived from the variable regions of the anti-R13 mAb 17.2 were expressed. scFv C5 was a dimer and bound to TcP2beta with an affinity of K(d) = 8 nM, whereas scFv B7 was monomeric and had less affinity than scFv C5 for TcP2beta, K(d) = 46 nM. The affinity constant of scFv C5 to the second extracellular loop of the human beta1-AR was of 10 microM. Moreover, scFv C5 induced an increase in cAMP levels of CHO-K cells transfected with the human beta1-AR; scFv B7 had no effect but blocked isoproterenol stimulation. The agonist-like activity of scFv C5 and the antagonist activity of scFv B7 were both confirmed in vivo on heart beating frequency after their passive transfer to mice. Molecular modeling of the variable region of mAb 17.2 indicated which amino acids were likely to be involved in recognizing both peptide EDDDMGFGLF, derived from the R13 epitope of TcP2beta, and peptide ESDEARRCYN from the second extracellular loop of the human beta1-AR. It is plausible that the recently described cross-reaction of mAb 17.2 with rhodopsin can also be explained by this model. The physiological effects of this type of anti-T. cruzi antibodies may increase the liability of patients with Chagas disease.

[Aortoenteric fistula as cause of digestive bleeding in three adult patients]. / Fistula aortoentérica como causa de hemorragia digestiva en tres pacientes adultos.

The purpose of this presentation is to report three adult patients with aortoenteric fistula whose initial presentation was abdominal pain and digestive bleeding. We stress the low incidence of this disease as a cause of digestive bleeding, its high mortality and the need of high clinical suspicion for its diagnosis. We discuss the different sites of the aortoenteric fistulas, probable physiopathological mechanisms that generate them and their elevated association with the presence of vascular prostheses.

The beta1 adrenergic effects of antibodies against the C-terminal end of the ribosomal P2beta protein of Trypanosoma cruzi associate with a specific pattern of epitope recognition.

BALB/c mice immunized with recombinant Trypanosoma cruzi ribosomal P2beta protein (TcP2beta) develop a strong and specific antibody response against its 13 residue-long C-terminal epitope (peptide R13: EEEDDDMGFGLFD) that has a concomitant beta1-adrenergic stimulating activity. However, other animals that undergo similar immunizations seem tolerant to this epitope. To evaluate further the antibody response against the ribosomal P proteins, 25 BALB/c and 25 Swiss mice were immunized with TcP2beta. From the 50 animals, 31 developed a positive anti-R13 response, whereas 19 were non-responsive. From the 31 anti-R13 positive mice, 25 had anti-R13 antibodies that recognized the discontinuous motif ExDDxGF, and their presence correlated with the recording of supraventricular tachycardia. The other six had anti-R13 antibodies but with a normal electrocardiographic recording. These anti-R13 antibodies recognized the motif DDxGF shared by mammals and T. cruzi and proved to be a true anti-P autoantibody because they were similar to those elicited in Swiss, but not in BALB/c mice, by immunization with the C-terminal portion of the mouse ribosomal P protein. Our results show that the recognition of the glutamic acid in position 3 of peptide R13 defines the ability of anti-R13 antibodies to react with the motif AESDE of the second extracellular loop of the beta1-adrenergic receptor, setting the molecular basis for their pathogenic beta1 adrenoceptor stimulating activity.

An exploratory study on cultural variations in oral health attitudes, behaviour and values of freshman (first-year) dental students.

OBJECTIVE: To identify similarities and differences in oral health attitudes, behaviour and values among freshman dental students. DESIGN: Cross-cultural survey of dental students. SETTING: 18 cultural areas. PARTICIPANTS AND METHODS: 904 first-year dental students completed the Hiroshima University-Dental Behavioural Inventory (HU-DBI) translated into their own languages. Individual areas were clustered by similarity in responses to the questions. RESULTS: The first group displayed an 'occidental-culture orientation' with the exception of Brazil (Cluster 1 comprised: Australia, United Kingdom, Ireland, Belgium and Brazil, Cluster 2: Germany, Italy, Finland and France). The second group displayed an 'oriental-cultural orientation' with the exception of Greece and Israel (Cluster 3 comprised: China and Indonesia, and Cluster 4: Japan, Korea, Israel, Hong Kong, Malaysia, Thailand and Greece). Australia and United Kingdom were the countries that were most alike. Ireland was the 'neighbour' to these countries. Greece and Malaysia had similar patterns of oral health behaviour although geographic conditions are very different. Although it was considered that in Hong Kong, occidental nations have affected the development of education, it remained in the oriental-culture group. Comparison with the data from the occidentals indicates that a higher percentage of the orientals put off going to the dentist until they have toothache (p < 0.001). Only a small proportion of the occidentals (8%) reported a perception of inevitability in having false teeth, whereas 33% of the orientals held this fatalistic belief (p = 0.001). CONCLUSIONS: Grouping the countries into key cultural orientations and international clusters yielded plausible results, using the HU-DBI.