ω-Conotoxina MVIIC e células-tronco mesenquimais promovem recuperação motora em ratos Wistar após trauma medular agudo / ω-Conotoxin MVIIC and mesenchymal stem cells promote motor recovery in Wistar rats after acute spinal cord injury]

O objetivo deste estudo foi avaliar o efeito da ω-conotoxina MVIIC e das células-tronco mesenquimais (CTM) de forma isolada e sua associação nos ratos submetidos ao trauma medular agudo (TMA). Trinta Rattus novergicus, linhagem Wistar, três meses de idade, foram distribuídos igualmente em cinco grupos experimentais: controle negativo (CN), controle positivo (CP), ω-conotoxina MVIIC (MVIIC), células-tronco mesenquimais da medula óssea (CTM-MO) e associação (MVIIC + CTM-MO). O grupo CN foi submetido à laminectomia sem trauma medular, e os grupos CP, MVIIC, CTM-MO e MVIIC + CTM-MO foram submetidos ao trauma medular contusivo. O grupo CP recebeu, uma hora após o TMA, 10µL de PBS estéril, e os grupos MVIIC e MVIIC + CTM-MO receberam 10µL de PBS contendo 20pmol da ω-conotoxina MVIIC, todos por via intratecal. Os grupos CTM-MO e MVIIC + CTM-MO receberam, 24 horas após, 1x106 de CTM via intravenosa. Avaliou-se a recuperação da função locomotora até o sétimo dia pós-trauma. Os animais tratados com MVIIC + CTM-MO obtiveram recuperação motora após o trauma medular agudo (P<0,05). Conclui-se que essa associação apresentou efeito neuroprotetor com melhora na função locomotora em ratos Wistar.(AU)

The objective of this study was to evaluate the effect of isolated ω-conotoxin MVIIC and mesenchymal stem cells (MSCs) and its association in rats submitted to acute spinal cord injury (SCI). Thirty Rattus norvegicus, Wistar strain, three-month-old rats were randomly distributed in five experimental groups with six animals: negative control (CN), positive control (CP), ω-conotoxin MVIIC (MVIIC), bone marrow mesenchymal stem cells (CTM-MO) and the association (MVIIC + CTM-MO). The CN group underwent laminectomy without spinal cord trauma, and groups CP, MVIIC, CTM-MO and MVIIC + CTM-MO were submitted to contusive spinal cord trauma. The CP group received 10µl of PBS one hour after SCI, and groups MVIIC and MVIIC + CTM-MO received 10µl of PBS containing 20pmol of ω-conotoxin MVIIC, both intrathecally. Groups CTM-MO and MVIIC + CTM-MO received 1x106 of MSCs intravenously 24 hours later. The recovery of locomotor function was evaluated up to seven days post-injury. The animals treated with MVIIC + CTM-MO obtained motor recovery after SCI (P<0.05). It is concluded that this association showed neuroprotective effect with improvements in locomotor function in Wistar rats.(AU)

Different outcomes of a cardiac rehabilitation programme in functional parameters among myocardial infarction survivors according to ejection fraction.

INTRODUCTION: Exercise-based cardiac rehabilitation (EBCR) is part of the management of patients who have suffered an acute myocardial infarction (AMI). Patients with a reduced ejection fraction (EF) comprise a higher-risk subgroup and are referred less often for these programmes. This study aimed at assessing the impact of the baseline EF on the functional benefits, as assessed by peak oxygen uptake (pVO2) and exercise duration, of an EBCR programme in AMI survivors. METHODS: Observational, retrospective cohort study including all patients admitted to a tertiary centre due to an AMI who completed a phase II EBCR programme after discharge, between November 2012 and April 2017. Functional parameters were assessed by a symptom-limited cardiopulmonary exercise test. RESULTS: A total of 379 patients were included [40.9% with reduced EF (<50%) at discharge]. After the programme, pVO2 and exercise duration increased significantly (p < 0.001). Patients with a reduced EF had a lower pVO2 and completed a shorter duration of exercise at the beginning and end of the programme. This group presented a higher increase in pVO2 (p = 0.001) and exercise duration (p = 0.007). This was maintained after adjusting for age, gender, history of coronary artery disease, number of sessions, Killip classification, arterial hypertension, dyslipidaemia, diabetes mellitus, smoking status and baseline pVO2. CONCLUSION: A phase II EBCR programme was associated with significant improvements in pVO2 and exercise duration among AMI survivors, irrespective of baseline EF classification. Those with a reduced baseline EF derived an even greater improvement, highlighting the importance of EBCR in this subgroup of patients.

Structural robustness of mammalian transcription factor networks reveals plasticity across development.

Network biology aims to understand cell behavior through the analysis of underlying complex biomolecular networks. Inference of condition-specific interaction networks from epigenomic data enables the characterization of the structural plasticity that regulatory networks can acquire in different tissues of the same organism. From this perspective, uncovering specific patterns of variation by comparing network structure among tissues could provide insights into systems-level mechanisms underlying cell behavior. Following this idea, here we propose an empirical framework to analyze mammalian tissue-specific networks, focusing on characterizing and contrasting their structure and behavior in response to perturbations. We structurally represent the state of the cell/tissue by condition specific transcription factor networks generated using DNase-seq chromatin accessibility data, and we profile their systems behavior in terms of the structural robustness against random and directed perturbations. Using this framework, we unveil the structural heterogeneity existing among tissues at different levels of differentiation. We uncover a novel and conserved systems property of regulatory networks underlying embryonic stem cells (ESCs): in contrast to terminally differentiated tissues, the promiscuous regulatory connectivity of ESCs produces a globally homogeneous network resulting in increased structural robustness. We show that this property is associated with a more permissive, less restrictive chromatin accesibility state in ESCs. Possible biological consequences of this property are discussed.

A comparison of two clinical scores for bronchiolitis. A multicentre and prospective study conducted in hospitalised infants

Background: There are a number of clinical scores for bronchiolitis but none of them are firmly recommended in the guidelines. Method: We designed a study to compare two scales of bronchiolitis (ESBA and Wood Downes Ferres) and determine which of them better predicts the severity. A multicentre prospective study with patients <12 months with acute bronchiolitis was conducted. Each patient was assessed with the two scales when admission was decided. We created a new variable "severe condition" to determine whether one scale afforded better discrimination of severity. A diagnostic test analysis of sensitivity and specificity was made, with a comparison of the AUC. Based on the optimum cut-off points of the ROC curves for classifying bronchiolitis as severe we calculated new Se, Sp, LR+ and LR- for each scale in our sample. Results: 201 patients were included, 66.7% males and median age 2.3 months (IQR = 1.3-4.4). Thirteen patients suffered bronchiolitis considered to be severe, according to the variable severe condition. ESBA showed a Se = 3.6%, Sp = 98.1%, and WDF showed Se = 46.2% and Sp = 91.5%. The difference between the two AUC for each scale was 0.02 (95%CI: 0.01-0.15), p = 0.72. With new cut-off points we could increase Se and Sp for ESBA: Se=84.6%, Sp = 78.7%, and WDF showed Se = 92.3% and Sp = 54.8%; with higher LR. Conclusions: None of the scales studied was considered optimum for assessing our patients. With new cut-off points, the scales increased the ability to classify severe infants. New validation studies are needed to prove these new cut-off points (AU)

No disponible

A comparison of two clinical scores for bronchiolitis. A multicentre and prospective study conducted in hospitalised infants.

BACKGROUND: There are a number of clinical scores for bronchiolitis but none of them are firmly recommended in the guidelines. METHOD: We designed a study to compare two scales of bronchiolitis (ESBA and Wood Downes Ferres) and determine which of them better predicts the severity. A multicentre prospective study with patients <12 months with acute bronchiolitis was conducted. Each patient was assessed with the two scales when admission was decided. We created a new variable "severe condition" to determine whether one scale afforded better discrimination of severity. A diagnostic test analysis of sensitivity and specificity was made, with a comparison of the AUC. Based on the optimum cut-off points of the ROC curves for classifying bronchiolitis as severe we calculated new Se, Sp, LR+ and LR- for each scale in our sample. RESULTS: 201 patients were included, 66.7% males and median age 2.3 months (IQR=1.3-4.4). Thirteen patients suffered bronchiolitis considered to be severe, according to the variable severe condition. ESBA showed a Se=3.6%, Sp=98.1%, and WDF showed Se=46.2% and Sp=91.5%. The difference between the two AUC for each scale was 0.02 (95%CI: 0.01-0.15), p=0.72. With new cut-off points we could increase Se and Sp for ESBA: Se=84.6%, Sp=78.7%, and WDF showed Se=92.3% and Sp=54.8%; with higher LR. CONCLUSIONS: None of the scales studied was considered optimum for assessing our patients. With new cut-off points, the scales increased the ability to classify severe infants. New validation studies are needed to prove these new cut-off points.

Field Efficacy of a Metarhizium anisopliae-Based Attractant-Contaminant Device to Control Ceratitis capitata (Diptera: Tephritidae).

Biological control of Ceratitis capitata (Wiedemann) (Diptera: Tephritidae) using entomopathogenic fungi is being studied as a viable control strategy. The efficacy of a Metarhizium anisopliae (Metschnikoff) Sorokin (Hypocreales: Clavicipitaceae)-based attractant-contaminant device (ACD) to control C. capitata was evaluated in a medium-scale (40 ha) 2-yr field trial using a density of 24 ACD per ha. Results showed that this density was adequate to efficiently reduce fruitfly populations and that the inoculation dishes (IDs) needed replacing mid-season to provide protection for the entire season. In this study, fungal treatment was even more effective than conventional chemical treatment. Population dynamics in fungus-treated fields along with the infectivity study of field-aged IDs in the laboratory found that the ACD remained effective for at least 3 mo. The results suggest M. anisopliae-based ACD can be used to control C. capitata in the field. The implications of its use, especially as a tool in an integrated pest management program, are discussed.

Studies on the codling moth (Lepidoptera: Tortricidae) response to different codlemone release rates.

The response of the codling moth (Cydia pomonella L. (Lepidoptera: Tortricidae)) to different emission values of its main pheromone component, 8E,10E-dodecadien-1-ol (codlemone), was investigated in three field trials conducted in plots without mating disruption treatments. Moth catches obtained in traps baited with pheromone dispensers were correlated with the corresponding codlemone release rates by multiple regression analysis. In a preliminary trial conducted in Lleida (NE Spain), a decreasing trend of captures was observed based on increasing pheromone levels. After this, the pheromone release profiles of the pheromone dispensers were studied, in parallel with the field trials, by residual codlemone extraction and gas chromatography quantification. In the trials carried out in Asturias (NW Spain), a correlation between trap catches and emission levels (within the range from 11 to 1,078 µg/d) was found and fitted a logarithmic model. Captures followed a decreasing linear trend in the range of emission rates from 11 to 134 µg/d. Given that release values comprised between 11 and 67 µg/d did not lead to significantly different catches in traps, this emission range could be considered to develop effective formulations for attraction purposes when mating disruption is not acting in the environment.

Euphorbia characias as bioenergy crop: a study of variations in energy value components according to phenology and water status.

Euphorbia characias has drawn much attention as a potential bioenergy crop given its considerable amount of latex, rich in hydrocarbon-like compounds, and its ability to grow in large areas of semiarid lands. Compositions of major constituents with an energy value have been determined for the three phenological stages of this plant (preflowering, flowering, and postflowering) and different irrigation treatments. Metabolites from both nonpolar and polar extracts have been identified and quantified by GC-MS, GC-FID, HPLC-ELSD, and UPLC-PDA-MS. The results highlight that the end of the flowering period is the optimal harvesting time to maximize the yields of E. characias as a potential energy crop. The total water requirements to obtain the maximum yields of hexane- and methanol-extractables were determined for its annual development cycle.

Advances in the use of trapping systems for Rhynchophorus ferrugineus (Coleoptera: Curculionidae): traps and attractants.

Given the social importance related to the red palm weevil, Rhynchophorus ferrugineus Olivier (Coleoptera: Curculionidae), efforts are being made to develop new control methods, such as the deployment of trapping systems. In this work, the efficacy of a new black pyramidal trap design (Picusan) has been verified in comparison with white and black buckets. In addition, the attractant and synergistic effect of ethyl acetate (EtAc) at different release levels has been evaluated under field conditions. The results show that Picusan traps captured 45% more weevils than bucket-type traps, offering significantly better trapping efficacy. The addition of water to traps baited with palm tissues was found to be essential, with catches increasing more than threefold compared with dry traps. EtAc alone does not offer attractant power under field conditions, and the release levels from 57 mg/d to 1 g/d have no synergistic effect with ferrugineol. Furthermore, significantly fewer females were captured when EtAc was released at 2 g/d. The implications of using EtAc dispensers in trapping systems are discussed.

Chemosterilant bait stations coupled with sterile insect technique: an integrated strategy to control the Mediterranean fruit fly (Diptera: Tephritidae).

During 2008 and 2009, the efficacy of the combination of two Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), control techniques, sterile insect technique (SIT) and a chemosterilant bait station system (Adress), was tested in three crops: citrus (Citrus spp.), stone fruit (Prunus spp.), and persimmon (Diospyros spp.). Two thousand sterile males were released per ha each week in the whole trial area (50,000 ha, SIT area). For 3,600 ha, within the whole trial area, 24 Adress traps per ha were hung (SIT + Adress area). Ten SIT + Adress plots and 10 SIT plots in each of three different fruit crops were arranged to assess Mediterranean fruit fly population densities and fruit damage throughout the trial period. To evaluate the efficacy of each treatment, the male and female populations were each monitored from August 2008 to November 2009, and injured fruit was assessed before harvest. Results showed a significant reduction in the C. capitata population in plots treated with both techniques versus plots treated only with the SIT. Likewise, a corresponding reduction in the percentage of injured fruit was observed. These data indicate the compatibility of these techniques and suggest the possibility of using Adress coupled with SIT to reduce C. capitata populations in locations with high population densities, where SIT alone is not sufficiently effective to suppress fruit fly populations to below damaging levels.

Carbonic anhydrase-related protein VIII is expressed in rod bipolar cells and alters signaling at the rod bipolar to AII-amacrine cell synapse in the mammalian retina.

Mutation of the gene encoding carbonic anhydrase-related protein VIII (CAVIII) results in motor coordination deficits in mice and humans, due to loss of this protein in Purkinje cells of the cerebellum. Recent studies have indicated that the CAVIII gene, Car8, is also expressed in rod bipolar cells (RBCs), a critical glutamatergic neuron for scotopic vision. We investigated the localization of CAVIII in the mouse and macaque retina, and utilized the wdl mouse, which has a null mutation in the Car8 gene, to determine how the loss of CAVIII affects retinal signaling. CAVIII immunoreactivity was observed in RBCs, with particularly high staining intensity in the axon terminals. In addition, weaker staining was observed in a subset of cone bipolar cells and γ-aminobutyric acid (GABA)ergic amacrine cells. Light-evoked current and voltage responses of RBCs were not altered in the wdl mutant. However, light-evoked current responses from the AII-amacrine cell, a postsynaptic partner at the RBC ribbon synapse, were significantly larger, and more prolonged than in control mice. These changes could not be attributed to alterations in calcium current activation or inactivation, or to changes in the density of RBCs. Furthermore, no gross synaptic alterations were evident in the wdl mutant at the light or ultrastructural level. These data provide evidence that the CAVIII protein, which is highly conserved in vertebrates, is selectively expressed within neural circuits, and may be important for modulating retinal neurotransmission.

High HTLV-1 proviral load, a marker for HTLV-1 associated myelopathy/tropical spastic paraparesis, is also detected in patients with infective dermatitis associated with HTLV-1

Salvador (BA, Brazil) is an endemic area for human T-cell lymphotrophic virus type 1 (HTLV-1). The overall prevalence of HTLV-1 infection in the general population has been estimated to be 1.76%. HTLV-1 carriers may develop a variety of diseases such as adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with HTLV-1 (IDH). IDH is a chronic and severe form of childhood exudative and infective dermatitis involving mainly the scalp, neck and ears. It has recently been observed that 30% of patients with IDH develop juvenile HAM/TSP. The replication of HTLV-1 has been reported to be greater in adult HAM/TSP patients than in asymptomatic HTLV-1 carriers. In the current study, the proviral load of 28 children and adolescents with IDH not associated with HAM/TSP was determined and the results were compared to those obtained in 28 HTLV-1 adult carriers and 28 adult patients with HAM/TSP. The proviral load in IDH patients was similar to that of patients with HAM/TSP and much higher than that found in HTLV-1 carriers. The high levels of proviral load in IDH patients were not associated with age, duration of illness, duration of breast-feeding, or activity status of the skin disease. Since proviral load is associated with neurological disability, these data support the view that IDH patients are at high risk of developing HAM/TSP.

High HTLV-1 proviral load, a marker for HTLV-1 associated myelopathy/tropical spastic paraparesis, is also detected in patients with infective dermatitis associated with HTLV-1.

Salvador (BA, Brazil) is an endemic area for human T-cell lymphotrophic virus type 1 (HTLV-1). The overall prevalence of HTLV-1 infection in the general population has been estimated to be 1.76%. HTLV-1 carriers may develop a variety of diseases such as adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with HTLV-1 (IDH). IDH is a chronic and severe form of childhood exudative and infective dermatitis involving mainly the scalp, neck and ears. It has recently been observed that 30% of patients with IDH develop juvenile HAM/TSP. The replication of HTLV-1 has been reported to be greater in adult HAM/TSP patients than in asymptomatic HTLV-1 carriers. In the current study, the proviral load of 28 children and adolescents with IDH not associated with HAM/TSP was determined and the results were compared to those obtained in 28 HTLV-1 adult carriers and 28 adult patients with HAM/TSP. The proviral load in IDH patients was similar to that of patients with HAM/TSP and much higher than that found in HTLV-1 carriers. The high levels of proviral load in IDH patients were not associated with age, duration of illness, duration of breast-feeding, or activity status of the skin disease. Since proviral load is associated with neurological disability, these data support the view that IDH patients are at high risk of developing HAM/TSP.

Infective dermatitis has similar immunological features to human T lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis.

Human T lymphotropic virus-type 1 (HTLV-1) is the causal agent of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), adult T cell leukaemia/lymphoma and infective dermatitis associated with HTLV-1 (IDH). Over-production of proinflammatory cytokines and an increase in HTLV-1 proviral load are features of HAM/TSP, but the immunological basis of IDH has not been established. In addition to severe cutaneous manifestations, the importance of IDH relies on the observation that up to 30% of children with IDH develop HAM/TSP in childhood and adolescence. In this study we determined the immune response in patients with IDH measuring interleukin (IL)-4, IL-5, IL-10, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha levels as well as the HTLV-1 proviral load. Additionally, regulatory cytokines and anti-cytokines were added to cultures to evaluate the ability of these molecules to down-modulate TNF-alpha and IFN-gamma synthesis. HTLV-1 carriers and patients with HAM/TSP served as controls. TNF-alpha and IFN-gamma levels were higher in IDH than in HTLV-1 carriers. There was no difference in IFN-gamma and TNF-alpha concentrations in IDH and HAM/TSP patients. There was a tendency for higher IL-4 mRNA expression and immunoglobulin E (IgE) levels in IDH than in HTLV-1 carriers, but the difference did not reach statistical significance. The HTLV-1 proviral load was significantly higher in IDH patients than in HTLV-1 carriers. IDH is characterized by an exaggerated Th1 immune response and high HTLV-1 proviral load. The similarities between the immunological response in patients with IDH and HAM/TSP and the high proviral load observed in IDH provide support that IDH is a risk factor for development of HAM/TSP.

The first account of the mating disruption technique for the control of California red scale, Aonidiella aurantii Maskell (Homoptera: Diaspididae) using new biodegradable dispensers.

Semiochemical-based pest management programs have been increasingly used to provide environmentally friendly methods for the control of major insect pests. The efficacy of the mating disruption technique has been demonstrated for several moth pests. Unfortunately, not many experiments on mating disruption to control diaspididae species have been documented. In this work, biodegradable dispensers for mating disruption with increasing pheromone loads were used in order to study the potential of this technique for the control of Aonidiella aurantii Maskell. Field trial results demonstrated that dispensers loaded with 50 mg (a.i.) (20 g ha-1) and 100 mg (a.i.) (40 g ha-1) of sex pheromone were the most suitable, achieving significant reductions in male catches, compared to an untreated plot. In treated plots, virtually a 70% reduction in damage to fruit was recorded. Pheromone release profiles of all the dispensers were also studied under field conditions. We found that emission values >250 microg day-1 were the most suitable. This study suggests a new biodegradable dispenser capable of interfering with normal A. aurantii chemical communication. The use of mating disruption as a control method against A. aurantii is discussed.

Incidence of adult form of autoimmune hepatitis in Valencia (Spain).

BACKGROUND AND STUDY AIMS: There is little information on the incidence of autoimmune hepatitis (AIH) because on many occasions the disease can progress asymptomatically, different diagnostic criteria have been proposed during the last 20 years, and many epidemiological studies are based on retrospective clinical series. The aim of this study was to determine the incidence of AIH in the province of Valencia, Spain, during the year 2003. PATIENTS AND METHODS: The Services of Gastroenterology of eight acute-care reference hospitals in the province of Valencia, Spain, covering 1,774,736 inhabitants over 14 years of age, participated in a prospective study. All newly diagnosed patients with AIH between January 1, 2003 and December 31, 2003 were eligible. The diagnosis was based on criteria of the International Autoimmune Hepatitis Group revised in 1999. RESULTS: There were 19 new cases of AIH, 18 females and 1 male [mean (SD) age of 54.3 (11.2) years, range 23-73]. Incidence peaked in the 45-54 year age group. Eighteen cases were classified as AIH type 1 and one case as AIH type 2. The incidence rate of AIH for the year 2003 in people older than 14 years of age was 1.07 new cases per 100,000 inhabitants, with 1.96 cases per 100,000 inhabitants in females and 0.12 cases per 100,000 inhabitants in males. CONCLUSIONS: The 2003 annual incidence of AIH in Valencia, Spain, was similar to that reported in other European countries. AIH occurred more frequently in women and in the 45-54 year age group, type 1 being the most common.

[A clinical study of adult autoimmune hepatitis in Valencia, Spain]. / Estudio clínico de la hepatitis autoinmune del adulto en Valencia.

OBJECTIVE: the clinical phenotype of autoimmune hepatitis (AIH) varies among geographical areas. The aim of this study is to determine the salient features of AIH in adult patients from the province of Valencia, Spain. MATERIAL AND METHODS: eighty-one patients with AIH attended to in eight acute-care hospitals between 1994 and 2003. New patients diagnosed with AIH during year 2003 were evaluated prospectively. Data from patients currently attending follow-up visits and diagnosed before 2003 were collected retrospectively. RESULTS: a total of 94% of patients were females. Forty-three percent were asymptomatic, 27% had acute hepatitis, and 30% had chronic hepatitis. Type 1 AIH was diagnosed in 90% of cases. Type 2 AIH was more frequent in younger patients, and presented with an acute pattern. One third of patients had cirrhosis at onset. Patients with cirrhosis were older than 60 years more frequently. Immunosuppressants were given to 57 patients, with complete or partial remission in 87.7%. There were no significant differences in response to immunosuppression according to presentation pattern or AIH subtype. CONCLUSIONS: AIH in Valencia was predominantly diagnosed in asymptomatic women. Most cases were type 1, and in 25% of patients another autoimmune disease coexisted. At the time of diagnosis one third of patients had cirrhosis, particularly those over 60 years.

Estudio clínico de la hepatitis autoinmune del adulto en Valencia / No disponible

Introducción: existen factores geográficos que influyen en lascaracterísticas de la hepatitis autoinmune (HAI).Objetivo: conocer las características epidemiológicas, clínicasy respuesta al tratamiento de la hepatitis autoinmune en la provinciade Valencia.Material y métodos: se trata de un estudio realizado en ochohospitales de Valencia, recogiendo de forma prospectiva los casosde hepatitis autoinmune diagnosticados en el año 2003 y deforma retrospectiva los diagnosticados entre 1994 y 2002.Resultados: se incluyeron 81 pacientes con HAI, siendo el94% mujeres. La forma de presentación fue: 43% asintomático,27% hepatitis aguda y 30% enfermedad hepática crónica. La mayoría(90%) fueron del tipo 1, mientras que las de tipo 2 fueronmás jóvenes (p = 0,007) y con predominio de hepatitis aguda (p= 0,04). Existía otra enfermedad autoinmune en uno de cada 4casos. Al momento del diagnóstico una tercera parte de los pacientespresentaba cirrosis. La cirrosis se presentó sobre todo enpacientes de más de 60 años (p < 0,01) y sin diferencias según laformas clínica (p = 0,1). El tratamiento se indicó en 57 casos ycon respuesta –completa o parcial– en el 87,7%. No se encontrarondiferencias significativas en la respuesta terapéutica según laforma de presentación ni los tipos de hepatitis autoinmune.Conclusiones: en nuestra zona la hepatitis autoinmune deladulto se presenta sobre todo en mujeres y de manera asintomática.La mayoría es tipo 1 y en el 25% de los casos coexiste otraenfermedad autoinmune. Al diagnóstico la tercera parte presentacirrosis hepática, sobre todo en los que tienen más de 60 años

Objective: the clinical phenotype of autoimmune hepatitis(AIH) varies among geographical areas. The aim of this study is todetermine the salient features of AIH in adult patients from theprovince of Valencia, Spain.Material and methods: eighty-one patients with AIH attendedto in eight acute-care hospitals between 1994 and 2003. Newpatients diagnosed with AIH during year 2003 were evaluatedprospectively. Data from patients currently attending follow-upvisits and diagnosed before 2003 were collected retrospectively.Results: a total of 94% of patients were females. Forty-threepercent were asymptomatic, 27% had acute hepatitis, and 30%had chronic hepatitis. Type 1 AIH was diagnosed in 90% of cases.Type 2 AIH was more frequent in younger patients, and presentedwith an acute pattern. One third of patients had cirrhosisat onset. Patients with cirrhosis were older than 60 years morefrequently. Immunosuppressants were given to 57 patients, withcomplete or partial remission in 87.7%. There were no significantdifferences in response to immunosuppression according to presentationpattern or AIH subtype.Conclusions: AIH in Valencia was predominantly diagnosedin asymptomatic women. Most cases were type 1, and in 25% ofpatients another autoimmune disease coexisted. At the time of diagnosisone third of patients had cirrhosis, particularly those over60 years

Severe stomatitis complicating treatment with pegylated-interferon alpha-2a and ribavirin in an HCV-infected patient.

OBJECTIVE: To report a case of severe stomatitis probably induced by peginterferon alpha-2a. METHODS AND RESULTS: A 42-year-old man with chronic hepatitis C genotype 1b commenced treatment with peginterferon alpha-2a 180 microg subcutaneously weekly and ribavirin 1000 mg/d orally. Twenty-eight days after commencing treatment, the patient experienced difficulties with swallowing, dryness of the mouth, stomatitis, and pain. Diagnosis of stomatitis was made. He did not complain of any other adverse effect of peginterferon alpha-2a and ribavirin. Both medications were discontinued. The withdrawal of peginterferon alpha-2a was followed by the resolution of the oral lesions in three weeks. The patient was followed up in the outpatient clinic at one month and at three months, and he was asymptomatic. CONCLUSIONS: Manufacturers of peginterferon alpha-2a suggest that mouth ulceration, stomatitis, dysphagia, and glossitis are considered adverse reactions of this medication. In this case, the most likely cause of the stomatitis was considered to be peginterferon alpha-2a because of the close temporal relationship between exposure to the drug and onset of symptoms, as well as the rapid resolution of the symptoms and signs after peginterferon alpha-2a was discontinued. An objective causality assessment revealed that a adverse drug event was possible. Clinicians should be aware of this potentially adverse effect of a widely used drug.