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Resumen Objetivo El consenso de Baveno VI para el cribado endoscopico de varices esofagogastricas recomienda evitar la endoscopia en algunos pacientes. Bajo esta estrategia, podrian pasar desapercibidas lesiones no relacionadas con hipertension portal, algunas de ellas potencialmente graves. El objetivo de este estudio es determinar la prevalencia de dichas lesiones e identificar los factores clinicos asociados a las mismas. Pacientes y metodos Estudio transversal unicentrico sobre una cohorte consecutiva de pacientes cirroticos sometidos a endoscopia digestiva alta en el contexto de un programa de cribado de varices esofagogastricas entre noviembre del 2013 y noviembre del 2018. Se analizaron los factores de riesgo para la presencia de lesiones no relacionadas con hipertension portal mediante regresion logistica uni y multivariante. Resultados Se incluyo a 379 pacientes. La etiologia mayoritaria de la cirrosis fue etilica (n = 229; 60,4%). La prevalencia de lesiones endoscopicas no relacionadas con hipertension portal fue del 39,6% (n = 150). Entre los 96 pacientes con enfermedad peptica (25,3%) se tomo test de ureasa en 54 (56,2%), siendo positiva en 24 (44,4%). La presencia de lesiones endoscopicas no relacionadas con hipertension portal no estuvo influida por la edad (p = 1), el genero (p = 0,28), la funcion hepatica (MELD p = 0,20, Child-Pugh p = 0,77) o la presencia de datos ecograficos de hipertension portal (p = 0,14). Los pacientes fumadores presentaron tendencia a mayor prevalencia de lesiones endoscopicas no relacionadas con la hipertension portal (43,2% vs. 34,6%; p = 0,09), particularmente ulcera peptica (6,4% vs. 0,6%; p = 0,05) y duodenitis peptica (17,3% vs. 6,3%; p = 0,002). El tabaquismo activo fue el unico factor predictivo independiente de ulcus o duodenitis peptica (odds ratio = 2,56; intervalo de confianza del 95%: 1,18-5,56; p = 0,017). Conclusiones El tabaquismo activo aumenta el riesgo de lesiones endoscopicas no relacionadas con hipertension portal, lo cual deberia ser investigado en profundidad para redefinir el cribado endoscopico en pacientes fumadores con cirrosis hepatica.

To determine the prevalence of endoscopic lesions unrelated with portal hypertension in patients with cirrhosis.Cross-sectional study including a consecutive cohort of patients with liver cirrhosis enrolled in a screening program of oesophageal varices who underwent an upper gastrointestinal endoscopy from November, 2013, to November, 2018. Clinical predictors of endoscopic lesions unrelated to portal hypertension were analyzed by univariate and multivariate logistic regression.A total of 379 patients were included. The most frequent aetiology of liver disease was alcohol consumption (60.4%). The prevalence of endoscopic lesions unrelated with portal hypertension was 39.6% (n=150). Among 96 patients with peptic lesions, urease was obtained in 56.2% of patients (positive in 44.4% of them). The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. Smokers had a trend to increased prevalence of endoscopic lesions unrelated to portal hypertension (43.2% vs. 34.6%; p=0.09), particularly peptic ulcer (6.4% vs. 0.6%; p=0.05) and peptic duodenitis (17.3% vs. 6.3%; p=0.002). Active smoking was the only independent predictor of peptic ulcer or duodenitis (OR=2.56; p=0.017).Active smoking is a risk factor for endoscopic lesions unrelated to portal hypertension. This finding should be further investigated to reassess endoscopic screening programs in cirrhotic smokers.

Background: This study aims to explore the feelings and experiences of nursing staff when faced with the death of a pediatric patient in the ICU. Methodology: A qualitative study based on hermeneutic phenomenology was conducted through semi-structured interviews. Ten nurses (30% of staff) from the Pediatric Intensive Care Unit of a referral hospital were interviewed in April 2022. Text transcripts were analysed using latent content analysis. Results: Content analysis indicated that the interviewees had feelings of sadness and grief; they had a misconception of empathy. They had no structured coping strategies, and those they practiced were learned through personal experience, not by specific training; they reported coping strategies such as peer support, physical exercise, or strengthening ties with close family members, especially their children. The lack of skills to cope with the death and the absence of support from personnel management departments were acknowledged. This can lead to the presence of compassion fatigue. Conclusions: The feelings that PICU nurses have when a child they care for die are negative feelings and sadness, and they possess coping strategies focused on emotions learned from their own experience and without institutional training support. This situation should not be underestimated as they are a source of compassion fatigue and burnout.

Antibiotic (Abx) treatments or inadvertent exposure to Abx-contaminated food and water can adversely affect health. Many studies show strong correlations between Abx and liver damage pointing to gut dysbiosis as a contributing factor because the gut microbiota (GM) forms a complex network with liver. Selenium (Se) is a beneficial micronutrient able to shape the composition of the GM. We analyzed here the ability of a low dose (120 μg/kg bodyweight/day) Se-enriched diet to ameliorate the effects of a 7-day intervention with an Abx-cocktail over the global health and the homeostasis of cholesterol and bile acids in the mouse liver. We found that Se restored lipid metabolism preventing the increased synthesis and accumulation of cholesterol caused by Abx treatment. Integrating these results with previous metataxonomic and metabolomic data in same mice, we conclude that part of the effect of Se against liver dysfunction (cholesterol and bile acids metabolism and transport) could be mediated by the GM. We provide data that contribute to a more complete view of the molecular mechanisms underlying the beneficial action of Se on health, pointing to a possible use of low doses of Se as a functional food additive (prebiotic) to prevent the negative effects of antibiotics.

Introduction: The benefit of intravenous thrombolysis (IVT) in wake-up stroke (WUS), stroke of unknown time of onset (SUKO), or when time exceeds 4.5 h from last-seen-normal (LSN) guided by CT perfusion (CTP) or MRI has been recently suggested. However, there is limited information of IVT in those patients in real-world studies. Objective: Our aim was to evaluate safety and efficacy of IVT selected by CTP in patients with WUS, SUKO, or stroke of time onset beyond 4.5 h. Material and Methods: We studied a prospective cohort of patients who underwent IVT from January 2010 to December 2017. Two groups were defined: standard of care group (SC) included patients with time onset 4.5 h from LSN with penumbra area in CTP. We evaluated baseline characteristics, functional outcomes according to modified Rankin Scale (mRS) at discharge and at 90 days, and intracranial hemorrhages rates. Results: 657 patients were studied: 604 (92%) were treated in the SC group and 53 (8%) in the CTP group. The mean NIHSS score was 9.8 in the CTP group versus 13 in the SC group (p = 0.001). Seventeen patients in the CTP group (32.1%) received bridging therapy with mechanical thrombectomy (MT). Last time seen well-to-needle time was 538 versus 155 min (p < 0.001). The incidence of symptomatic intracranial hemorrhage was equal in both groups (3.8 vs. 3.8%, p = 1). Good functional outcome (mRS < 2) was achieved in both groups (72 vs. 60.4%, p = 0.107). Conclusions: IVT in patients with WUS, SUKO, or stroke beyond >4.5 h from LSN, with salvageable brain tissue on CTP, seems to be safe and has similar functional outcomes at 90 days to the standard therapeutic window, even when combined with MT.

Skin mucus is considered the first barrier against diseases in fish. The skin mucus protein profile of the greater amberjack (Seriola dumerili) and its changes due to experimental infection with Neobenedenia girellae were studied by combining 2-DE-MS/MS and gel-free LC-MS/MS proteomic approaches. The 2-DE results led to the identification of 69 and 55 proteins in noninfected and infected fish, respectively, and revealed that keratins were specifically cleaved in parasitized fish. Therefore, the skin mucus of the infected fish showed a higher protease activity due to, at least in part, an increase of metal-dependent protease and serine-type protease activities. Additionally, through a gel-free LC-MS/MS analysis, 1377 and 1251 different proteins were identified in the skin mucus of healthy and parasitized fish, respectively. The functional analysis of these proteins demonstrated a statistical overrepresentation of ribosomal proteins (a well-known source of antimicrobial peptides) in N. girellae-infected fish. In contrast, the components of membranes and protein transport GO categories were underrepresented after infection. Immune system process-related proteins constituted 2.5% of the total skin mucosal proteins. Among these skin mucosal proteins, 14 and 15 proteins exclusive to non-parasitized and parasitized fish were found, respectively, including specific serine-type proteases and metalloproteases in the parasitized fish. Moreover, the finding of tryptic peptides exclusive to some bacterial genera, obtained by gel-free LC-MS/MS, allowed us to construct a preliminary map of the microbiota living in the mucus of S. dumerili, with Pseudomonas and Paracoccus the most represented genera in both noninfected and infected fish.

The benefit of intravenous thrombolysis (IVT) in wake-up stroke (WUS), stroke of unknown time of onset (SUKO), or when time exceeds 4.5 h from last-seen-normal (LSN) guided by CT perfusion (CTP) or MRI has been recently suggested. However, there is limited information of IVT in those patients in real-world studies.Our aim was to evaluate safety and efficacy of IVT selected by CTP in patients with WUS, SUKO, or stroke of time onset beyond 4.5 h.We studied a prospective cohort of patients who underwent IVT from January 2010 to December 2017. Two groups were defined: standard of care group (SC) included patients with time onset4.5 h and CTP group included patients with WUS, SUKO, or onset beyond4.5 h from LSN with penumbra area in CTP. We evaluated baseline characteristics, functional outcomes according to modified Rankin Scale (mRS) at discharge and at 90 days, and intracranial hemorrhages rates.657 patients were studied: 604 (92%) were treated in the SC group and 53 (8%) in the CTP group. The mean NIHSS score was 9.8 in the CTP group versus 13 in the SC group (p = 0.001). Seventeen patients in the CTP group (32.1%) received bridging therapy with mechanical thrombectomy (MT). Last time seen well-to-needle time was 538 versus 155 min (p0.001). The incidence of symptomatic intracranial hemorrhage was equal in both groups (3.8 vs. 3.8%, p = 1). Good functional outcome (mRS2) was achieved in both groups (72 vs. 60.4%, p = 0.107).IVT in patients with WUS, SUKO, or stroke beyond4.5 h from LSN, with salvageable brain tissue on CTP, seems to be safe and has similar functional outcomes at 90 days to the standard therapeutic window, even when combined with MT.

Senegalese sole (Solea senegalensis) has been proposed as a high-potential species for aquaculture diversification in Southern Europe. It has been demonstrated that a proper feeding regimen during the first life stages influences larval growth and survival, as well as fry and juvenile quality. The bacterial strain Shewanella putrefaciens Pdp11 (SpPdp11) has shown very good probiotic properties in Senegalese sole, but information is scarce about its effect in the earliest stages of sole development. Thus, the aim of this study was to investigate the effect of SpPdp11, bioencapsulated in live diet, administered during metamorphosis (10-21 dph) or from the first exogenous feeding of Senegalese sole (2-21 dph). To evaluate the persistence of the probiotic effect, we sampled sole specimens from metamorphosis until the end of weaning (from 23 to 73 dph). This study demonstrated that probiotic administration from the first exogenous feeding produced beneficial effects on Senegalese sole larval development, given that specimens fed this diet exhibited higher and less dispersed weight, as well as increases in both total protein concentration and alkaline phosphatase activity, and in non-specific immune response. Moreover, real-time PCR documented changes in the expression of a set of genes involved in central metabolic functions including genes related to growth, genes coding for proteases (including several digestive enzymes), and genes implicated in the response to stress and in immunity. Overall, these results support the application of SpPdp11 in the first life stages of S. senegalensis as an effective tool with the clear potential to benefit sole aquaculture.

espanolSe presenta un caso de alta frecuencia en la consulta de atencion primaria, como es una lesion quistica en la piel. La peculiaridad de este caso es el tratamiento quirurgico en esta localizacion que entrana ciertas complicaciones. Por tanto, es de obligado conocimiento por parte del medico el riesgo que supone la exeresis y dar maxima seguridad al paciente. La intencion del presente articulo es el abordaje integral de la lesion: por un lado, el aspecto puramente clinico/dermatologico y por otro, el tratamiento quirurgico. EnglishA case of high frequency is presented in the primary care consultation, as it is a cystic lesion on the skin. The peculiarity of this case is the surgical treatment, which involves certain complications at this location. Therefore, it is mandatory for the doctor to know the risk of exeresis and give maximum safety to the patient. The intention of this article is the comprehensive approach to the lesion: on the one hand, the purely clinical / dermatological aspect and on the other, the surgical treatment.

Resumen Introduccion En los pacientes que han recibido resecciones gastricas parciales, las dificultades para realizar la colangiopancreatografia retrograda endoscopica (CPRE) se ven aumentadas debido a la alteracion anatomica regional. Objetivo Revisar la experiencia de la CPRE en pacientes con gastrectomia parcial y gastroenteroanastomosis (GE) tipo Billroth II o con otras GE (Billroth I e indeterminadas) en nuestro centro. Material y metodos Se incluyeron todos los pacientes con gastrectomia parcial y GE que recibieron CPRE en un periodo de 19 anos. Resultados Se incluyeron 233 pacientes (91% varones y 9% mujeres) desde 1993 a 2012. El 88,4% los pacientes presentaban gastrectomia con GE Billroth II y el 11,6% otras GE, siendo la tasa de exito de la CPRE del 51,9 y 55,6%, respectivamente. Las causas mas frecuentes de fracaso fueron en primer lugar la imposibilidad de canulacion (44%) y la no identificacion de la papila (39,6%). El 31,8% de los pacientes presento coledocolitiasis como diagnostico final. El numero medio de sesiones fue de 1,09. El porcentaje de complicaciones fue del 2,6%. Conclusiones El grado de dificultad tecnica influye en el exito de la CPRE, por este motivo, en nuestro centro, tuvo una tasa de exito algo superior al 50%, pero con un escaso numero de complicaciones.

Resumen Fundamento y objetivo La valoracion del paciente con hemorragia digestiva (HD) aguda requiere de una evaluacion clinica y analitica precoz. El objetivo de este estudio es valorar la concordancia de la determinacion de hemoglobina (Hb) y hematocrito (HTC) precozmente mediante gasometria venosa (GSV) y de forma convencional por el Laboratorio (LAB) de Urgencias. Pacientes y metodo Estudio observacional y prospectivo de pacientes ingresados en la Unidad de Hemorragias Digestivas por HD aguda alta y baja. Se recogieron variables demograficas, clinicas y muestras de sangre venosa simultaneas para la determinacion de Hb y HTC por GSV y LAB. Se analizo la concordancia de ambos metodos mediante el coeficiente de correlacion intraclase (CCI) y el analisis de Bland-Altman. Resultados Se incluyeron 132 pacientes. Un total de 87 (65,9%) eran varones y la edad media fue de 66,8 anos. La GSV sobreestimo la Hb en 0,49 g/dl (intervalo de confianza del 95% 0,21-0,76) respecto al LAB. La concordancia fue muy buena en la Hb (CCI 0,931) y buena en el HTC (CCI 0,899), mostrando las graficas de Bland-Altman tanto la concordancia como la sobreestimacion de la determinacion de la Hb por GSV. En 19 pacientes (14,39%) la Hb por GSV supero en mas de 1 g/dl la determinacion final obtenida por LAB. Conclusiones La determinacion precoz de Hb y HTC en pacientes con HD aguda mediante GSV resulta fiable en la valoracion inicial de la anemia. La GSV sobreestima sistematicamente el valor de Hb en al menos 0,5 g/dl, por lo que la evaluacion clinica y hemodinamica del sangrante debe prevalecer sobre el resultado analitico.

Resumen Introduccion La dilatacion neumatica y la miotomia quirurgica son actualmente los tratamientos de eleccion de la acalasia sintomatica. La seleccion de una u otra como primera opcion depende de la experiencia de cada centro y de las preferencias del paciente. Objetivo Revisar la experiencia en nuestro centro de la dilatacion neumatica en pacientes con acalasia. Material y metodos Se incluyeron todos los pacientes con diagnostico clinico, endoscopico y manometrico compatible con acalasia a los que se les practico una dilatacion neumatica en un periodo de 19 anos. Todas las dilataciones se realizaron de forma sistematica con un balon Rigiflex ® , en la mayoria de los casos con presiones de 250, 250 y 300 mmHg en 3 tiempos de un minuto separados por un minuto de duracion. Se evaluo el exito de la dilatacion en funcion de la sintomatologia del paciente, numero de sesiones requeridas y necesidad de cirugia, asi como la presencia de complicaciones. Resultados Se incluyeron 171 pacientes, 53,2% varones y 46,8% mujeres, con una edad media de 51,53 ± 17,78 anos (16-87), desde junio de 1993 hasta octubre de 2012. En 157 pacientes se utilizo un balon de 35 mm, en 9 pacientes un balon de 30 mm y en 7 pacientes, uno de 40 mm. Del total de pacientes: 108 requirieron una sola sesion de dilatacion, 56 dos sesiones con un tiempo medio entre la primera y la segunda sesion de 25,23 ± 43,25 meses (1-215) y 7 pacientes, 3 sesiones con un tiempo medio entre la segunda y la tercera sesion de 6,86 ± 5,33 meses (1-15). El 82% de los pacientes presentaron una buena evolucion tras la dilatacion, considerandose esta exitosa. De los 140 pacientes que presentaron respuesta, 121 tuvieron respuesta completa (desaparicion total de los sintomas sin reaparicion de los mismos) y 19 respuesta parcial (desaparicion inicial de los sintomas con posterior reaparicion). Un 15,8% de los pacientes requirieron cirugia (miotomia de Heller). En 4 de los 171 pacientes hubo complicacion de la tecnica, siendo todas ellas perforaciones que se resolvieron satisfactoriamente, 2 de ellas con tratamiento conservador y otras 2 de forma quirurgica. No hubo ningun evento de mortalidad en relacion con la tecnica ni con las complicaciones de la misma. Conclusiones En nuestra serie, la dilatacion neumatica presento una alta tasa de exito, en la mayoria de los casos con una unica sesion, y un escaso porcentaje de complicaciones, por lo que demuestra ser una tecnica eficaz y segura para estos pacientes, evitando un gran numero de intervenciones quirurgicas.

Peroxiredoxin 1 (PRDX1) is a member of the peroxiredoxin family. Aberrant expression of PRDX1 has been described in various cancers. We investigated the significance of this up-regulation in non-challenged hepatocellularcarcinoma (HCC) cells by establishing a HepG2 cell line stably expressing a Prdx1 shRNA. Prdx1 silencing reversed, at least partially, the tumoural phenotype of HepG2 cells, resulting in morphological changes, delayed cell growth, down-regulation of transcripts for AFP, osteopontin and β-catenin and decreased γ-glutamyl transpeptidase activity, and oppositely up-regulation of transcripts for E-cadherin and proapoptotic proteins (BAX, CASP3) and increased alkaline phosphatase and CASP3 activities. Proteomic profiling identified 16 spots differentially expressed in Prdx1-silenced cells. Most of the variations involved the down-regulation of proteins with pivotal roles in cell proliferation and differentiation, in agreement with the observed phenotypic changes. We also investigated the effect of Prdx1 silencing on thiol protein oxidation. Proteins prone to reversible cysteine oxidation play major physiological functions. Notably, the down-regulation and altered redox status of key enzymes of carbohydrate and amino acid metabolism suggested a disturbance of the Warburg effect and glutamine utilization, two major pathways in the proliferation of tumour cells. Overall, these observations suggest that PRDX1 acts as a pro-cancer protein in HCC HepG2 cells.

The oxidation and reduction of cysteine thiols are thought to be a major mechanism for redox regulation. The aim of this study was to identify proteins with reactive thiols and determine their oxidation profiles under oxidative stress induced by simultaneous silencing of antioxidant defences (peroxiredoxin-1, peroxiredoxin-3, and the catalytic subunit of the glutamate-cysteine ligase), and/or treatment with glucose oxidase (GO). Using an approach that combined the labelling of reversibly oxidised cysteines, 2-DE protein separation and MS analysis, we identified 26 proteins with cysteines prone to reversible oxidation belonging to different functional classes. Among these proteins are those that have not been previously recognised as reversible oxidation targets, including cytoplasmic aspartate aminotransferase, proteasome subunit alpha type-6, heterogeneous nuclear ribonucleoproteins isoA2/B1 and A/B, and histidine triad nucleotide-binding protein 1. We provide the first evidence of reversible oxidation for specific cysteines, including Cys112 and Cys146 in glutamate dehydrogenase 1, Cys17 in actins, Cys5 in protein disulfide-isomerase A3, and Cys267 in the heat shock cognate 71 kDa protein. Silencing induced lower oxidative stress than GO treatment. Nevertheless, we detected some proteins particularly sensitive to oxidation by silencing. We hypothesised that these proteins may play a role in regulatory mechanisms by redox stress.

Eosinophilic esophagitis is an underdiagnosed disease that should be suspected in all patients with dysphagia and food impaction. Although these are the leading symptoms, the clinical and endoscopic spectrum is highly varied. Clinicians should be aware of the risk of endoscopy-related complications in this disorder. Precautions should be maximized in endoscopic examinations to avoid iatrogenic damage. We describe the case of a young patient with esophageal stricture and dysphagia who suffered a perforation following a biopsy.

Ischemic gastropathy is highly infrequent in daily medical practice. In the last few years, the number of reported cases has increased. Although the guiding symptom is usually abdominal pain, the clinical spectrum of the disease is highly variable. Early diagnosis and treatment are essential to change the natural history of the disease. We present the case of a 75-year-old man with chronic abdominal pain who developed a fulminant form of necrotizing gastric ischemia and died within less than 24 h.

The present work shows the possibilities of metallomics to characterize metal-linking proteins in Mus Musculus that could be used in environmental assessment. The laboratory mouse M. musculus is used as reference of gene/protein sequence databases to address methodological approaches based on changes in transcripts regulation, proteins expression and metalloproteins profiles in the environmental bioindicator Mus spretus that has been demonstrated to be genetically homologous to M. Musculus . A metallomic approach using size exclusion chromatography with inductively coupled plasma-mass spectrometry detection (SEC–ICP-MS) was applied to cytosolic extracts from different M. musculus organs: lung, liver, spleen, kidney, brain, testicle, hearth and muscle. The resulting profiles of metallobiomolecules revealed the presence of a Cu-binding fraction in the 7–10 kDa range which was not present in the other tissues, can be associated to low molecular mass metallothionein-like proteins. The application of reverse phase chromatography with ICP-MS detection to this fraction gives two peaks that have been isolated for later identification by tandem mass spectrometry. The mass balance of copper evaluated by ICP-MS analysis of the digested brain fractions isolated by SEC and RP chromatography reveals good recoveries of the separations. The application of 2-DE to both crude brain extract and SEC fraction (7–10 kDa) reveals the considerably reduction of the number of proteins confirming that a good purification has been attained by SEC. This integration of metallomics with proteomics and transcriptomics can be useful in further studies involving the free-living mouse M. spretus for assessment of environmental issues.

Here we report a preliminary working scheme for the integrative application of transcriptomic, proteomic, and metallomic methodologies in environmental monitoring, by using as sentinel the wildlife species Mus spretus and as reference the gene/protein sequence databases from the key model species Mus musculus. We have demonstrated that the absolute transcript expression signatures quantified by reverse transcription (RT) and real-time polymerase chain reaction (PCR) of selected key genes (e.g., those coding for biotransformation enzymes) in M. spretus is a useful and reliable novel biomonitoring end-point. The suitability of commercial M. musculus oligonucleotide arrays for genome-wide transcriptional profiling in M. spretus has been also shown. Transcriptomic studies indicate considerable gene sequence similarities between both mouse species. Based on these similarities, we have demonstrated the applicability in free-living M. spretus of high-throughput proteomic methods, based on matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry (MALDI-TOFMS) analysis of tryptic 2D electrophoresis (2-DE) spot digest and peptide matching with M. musculus database. A metallomic approach based on size exclusion chromatography inductively coupled plasma-mass spectrometry (SEC-ICP-MS) was applied to trace metal-biomolecule profiles. A preliminary integration of these three -omics has been addressed to M. musculus/M. spretus couple, two rodent species that separated 3 million years ago. The integrated application of transcriptomic and proteomic data and the bidirectional use of metallomics and proteomics for selective isolation of metal-biomolecules are covered in the working scheme MEPROTRANS-triple-OMIC reported in this study.

Background and aims MELD allocation system has changed the clinical consequences on waiting list (WL) for LT, but its impact on mortality has been seldom studied. We aimed to assess the ability of MELD and other prognostic scores to predict mortality after LT. Methods 301 consecutive patients enlisted for LT were included, and prioritized within WL by using the MELD-score according to: hepatic insufficiency (HI), refractory ascites (RA) and hepatocellular carcinoma (HCC). The analysis was performed to predict early mortality after LT (8 weeks). Results Patients were enlisted as HI (44.9%), RA (19.3%) and HCC (35.9%). The major aetiologies of liver disease were HCV (45.5%). Ninety-four patients (31.3%) were excluded from WL, with no differences among the three groups (p = 0.23). The remaining 207 patients (68.7%) underwent LT, being HI the most frequent indication (42.5%). HI patients had the shortest length within WL (113.6 days vs 215.8 and 308.9 respectively; p

Aquaculture industry exposes fish to acute stress events, such as high stocking density, and a link between stress and higher susceptibility to diseases has been concluded. Several studies have demonstrated increased stress tolerance of fish treated with probiotics, but the mechanisms involved have not been elucidated. Shewanella putrefaciens Pdp11 is a strain isolated from healthy gilthead seabream (Sparus aurata L.) and it is considered as probiotics. The aim of this study was to evaluate the effect of the dietary administration of this probiotics on the stress tolerance of Solea senegalensis specimens farmed under high stocking density (PHD) compared to a group fed a commercial diet and farmed under the same conditions (CHD). In addition, during the experiment, a natural infectious outbreak due to Vibrio species affected fish farmed under crowding conditions. Changes in the microbiota and histology of intestine and in the transcription of immune response genes were evaluated at 19 and 30 days of the experiment. Mortality was observed after 9 days of the beginning of the experiment in CHD and PHD groups, it being higher in the CHD group. Fish farmed under crowding stress showed reduced expression of genes at 19 day probiotic feeding. On the contrary, a significant increase in immune related gene expression was detected in CHD fish at 30 day, whereas the gene expression in fish from PHD group was very similar to that showed in specimens fed and farmed with the conventional conditions. In addition, the dietary administration of S. putrefaciens Pdp11 produced an important modulation of the intestinal microbiota, which was significantly correlated with the high number of goblet cells detected in fish fed the probiotic diet., SI

Fish skin mucus is the first line of defense against infections and it discriminates between pathogenic and commensal bacterial strains. Mucus composition varies amongst fish species and is influenced by endogenous and exogenous factors. This study describes the first proteome map of the epidermal mucus of farmed gilthead seabream (Sparus aurata). We used an integrative proteomic approach by combining a label-free procedure (LC-MS/MS) with the classical 2-DE-PMF-MS/MS methodology. The identified mucosal proteins were clustered in four groups according to their biological functions. Structural proteins (actins, keratins, tubulins, tropomyosin, cofilin-2 and filamin-A) and metabolic proteins (ribosomal proteins, proteasomal subunits, NACA, VCP, histones, NDPK, transferrin, glycolytic enzymes, ATP synthase components, beta-globin, Apo-A1 and FABP7) were the best represented functional categories. We also found proteins involved in stress response (WAP65, HSPC70, Cu,Zn-SOD, and PRDX1 and PRDX2) and signal transduction (PP2A 65 kDa regulatory subunit, 14-3-3 protein beta/alpha, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, RhoGDI and PEBP1). Most of the identified proteins address different aspects of the innate immune response. Additionally, we analyzed bacterial peptides identified in the skin mucus of healthy S. aurata. These results revealed that genera belonging to the Lactobacillales order constitute the most abundant microorganism populations in this habitat. Biological significance This work shows that proteomic methods can be used to characterize fish skin mucus. Using a coupled approach of LC-MS/MS and a 2-DE-PMF-MS/MS, we have obtained the first comprehensive view of the skin mucosal proteome of S. aurata, a fish species that is economically relevant for Mediterranean aquaculture. We identified a panel of proteins involved in a variety of biological functions, particularly in the innate immune response. Furthermore, to our knowledge, this is the first time a proteomic approach has been used to examine the microbiota in the skin mucus of a fish species. Overall, these results support further immunological researches in S. aurata and are relevant for the culture of this important fish species.

Escherichia coli has two aerobic ribonucleotide reductases encoded by the nrdAB andnrdHIEF operons. While NrdAB is active during aerobiosis, NrdEF is considered a cryptic enzyme with no obvious function. Here, we present evidence that nrdHIEF expression might be important under certain circumstances. Basal transcript levels were dramatically enhanced (25–75-fold), depending on the growth-phase and the growth-medium composition. Likewise, a large increase of >100-fold in nrdHIEF mRNA was observed in bacteria lacking Trx1 and Grx1, the two main NrdAB reductants. Moreover, nrdHIEFexpression was triggered in response to oxidative stress, particularly in mutants missing hydroperoxidase I and alkyl-hydroperoxide reductase activities (69.7-fold) and in cells treated with oxidants (up to 23.4-fold over the enhanced transcript level possessed by cells grown on minimal medium). The mechanism(s) that triggers nrdHIEFexpression remains unknown, but our findings exclude putative global regulators like RpoS, Fis, cAMP, OxyR, SoxR/S, or RecA. What we have learned about nrdHIEF expression indicates strong differences between its regulation and that of thenrdAB operon and of genes coding for components of both thioredoxin/glutaredoxin pathways. We propose that E. colimight optimize the responses to different stimuli by co-evolving the expression levels for its multiple reductases and electron donors.

We examined the in vivo expression of up to 16 genes encoding for components of both glutaredoxin and thioredoxin systems and for members of the OxyR and SoxRS regulons. We demonstrated that grxA (Grx1) transcription is triggered in bacteria lacking Trx1 (trxA) and GSH (gshA) in an OxyR-dependent manner. We also indicated that, unlike OxyR, SoxR is not constitutively activated in the oxidizing environment of trxA gshA mutants. We discovered that the lack of Trx1 plus GSH increases the steady-state levels of Trx reductase (trxB) and Trx2 (trxC) transcripts. This increase and the trxB and trxC up-regulation caused by the constitutive oxyR2 allele indicate that OxyR also plays a role in the regulation of the thioredoxin pathway. On the contrary, no change in the expression of genes for Trx1, Grx2, and Grx3 was observed. Transcription of nrdAB (RRase) was not induced by oxidative stress yet was induced by hydroxyurea (RRase inhibitor). Induction level was as the enhanced nrdAB basal expression of trxA grxA mutants, indicating that RRase operation without Trx1 and Grx1 must lead to disturbances sensed as those caused by hydroxyurea. We also demonstrated an inverse relation between nrdAB expression and that of genes coding for components of both glutaredoxin (grxA, gorA) and thioredoxin (trxB, trxC) systems.

As a consequence of oxidative stress, reactive oxygen species are generated in the cells. They interact with DNA and induce various modifications. Among them, oxidised purines (such as C8-oxoguanine and purines whose imidazole ring is opened), oxidised pyrimidines (such as thymine and cytosine glycols, ring saturated and fragmented pyrimidines), ethenobases and hypoxanthine. These various lesions have either miscoding properties or are blocks for DNA and RNA polymerases during replication and transcription, respectively. Most of these lesions are repaired by the base excision pathway in which the first step is mediated by specific DNA glycosylases. We review the various glycosylases involved in the repair of oxidised bases in Escherichia coli. The Fpg protein (formamidopyrimidine-DNA glycosylase) contains a zinc finger and excises oxidised purines whereas the Nth protein excises oxidised pyrimidines. The Nei protein excises a comparable spectra of pyrimidines and is believed to act as a back up enzyme to the Nth protein. The hypoxanthine-DNA glycosylase excises hypoxanthine residue and is one of the various activities of the AlkA protein (including formyluracil and ethenopurines residues). The Nfo protein was shown to have a novel activity that incises 5' to an alpha-deoxyadenosine residue (the anomer of deoxyadenosine formed by gamma-irradiation). The mechanism of action of the Fpg and Nth proteins are discussed. The properties of the human counterpart of the Fpg and Nth proteins the hNth and OGG1 proteins, respectively are also reviewed.

Various forms of oxidative stress, including gamma-radiolysis and UV irradiation, result in the formation of damaged bases. (5R)-Thymidine C5-hydrate is one of several modified nucleosides produced from thymidine under these conditions. N-(2-Deoxy-beta-D-erythro-pentofuranosyl)-N-3-[(2R)-hydroxyisobutyric acid]urea or alphaRT is the respective fragmentation product formed from (5R)-thymidine C5-hydrate upon hydrolysis. This modified nucleoside has potential mutagenic or lethal properties. No enzymatic activity responsible for the removal of alphaRT has been identified. We report here that when present in DNA, alphaRT is a substrate for two purified enzymes from Escherichia coli involved in the repair of oxidized bases: the Nth and the Fpg proteins. The Fpg protein removes the alphaRT lesion more efficiently than the Nth protein. This is the first example of efficient excision of a ring-opened form of a pyrimidine by the Fpg protein. The high efficacy of the Fpg protein suggests that it is likely to be involved in vivo in the excision of alphaRT. The kinetics of the reaction of the Fpg protein with DNA containing alphaRT suggest substrate inhibition. Duplex oligodeoxynucleotides containing alphaRT positioned opposite T, dG, dC, and dA were cleaved efficiently by both enzymes, although the profiles of activity of the two enzymes were different. The Nth enzyme preferentially excises alphaRT when opposite a dG, followed by alphaRT.dA, alphaRT. T, and alphaRT.dC. For the Fpg protein, the order is alphaRT.dC >/= alphaRT.dG approximately alphaRT.T > alphaRT.dA. Moreover, we show that human cell extract exhibits an activity that excises alphaRT from an oligonucleotide, suggesting that human homologues of the Nth and/or Fpg proteins could be involved in repair of this lesion in human cells.

In the absence of nucleotide excision repair, the additional deficiency of the DNA alkyltransferase (ATase) encoded by the constitutive ogt gene of Escherichia coli caused a marked increment in mutation induction by N-propyl-N-nitrosourea (PNU). Irrespective of the presence or the absence of the Ogt ATase, little mutagenic response was detected in Uvr 1 bacteria in the concentration range 0-8 mM PNU, indicating that most premutagenic DNA lesions induced at these concentrations are efficiently recognized and repaired by the nucleotide excision repair system. Some increased susceptibility to mutagenesis by PNU was detected in Uvr Ogt + bacteria, but the Uvr - Ogt double mutant exhibited much higher sensitivity. These data suggest that the Ogt ATase can replace to a great extent the repair capacity of the (A(BC excinuclease. Forward mutations induced by 6 mM PNU within the initial part of the lacl gene were recovered from Uvr + Ogt , Uvr Ogt + , and Uvr Ogt bacteria. A total of 439 independent mutations were characterized by DNA sequence analysis. The PNU-induced spectra were dominated by G:C→A:T transitions, consistent with the major role of the O 6 -alkylguanine miscoding lesion in mutagenesis by alkylating agents. Specific sites for G:C→A:T transitions were recovered more or less frequently in one genetic background versus the others, giving statistically significant differences among the spectra (P < 10 -6 ). We examined the influence of DNA repair by (A)BC excinuclease and Ogt ATase on the 5'-flanking base and DNA-strand associated with the PNU-induced G:C→A:T transitions. Preferences different from those previously reported for the ethylating (ENU) and methylating (MNU) analogs were detected. We indicate that these differences might be caused by the PNU possibility of giving isopropyl adducts, in addition to the expected n-propyl adducts, and by possible preferences in the initial distribution of these lesions as well as in their repair by the (A)BC excinuclease and the Ogt ATase of coli.

In patients who have undergone partial gastric resections, the difficulty of performing endoscopic retrograde cholangiopancreatography (ERCP) is increased due to the resulting anatomic abnormality.To review our experience of ERCP in patients with Billroth II gastrectomy and other types of gastrectomy (Billroth I and indeterminate) in our center.We included all patients with Billroth II gastrectomy or other types of gastrectomy undergoing ERCP in a 19-year period.We included 233 patients (91% men and 9% women) from 1993 to 2012. A total of 88.4% of the patients had undergone Billroth II and 11.6% had undergone other types of gastrectomy, with an ERCP success rate of 51.9% and 55.6%, respectively. The most common causes of failure were inability to cannulate (44%) and failure to identify the papilla (39.6%). The final diagnosis was choledocholithiasis in 31.8%. The mean number of sessions was 1.09. The complications rate was 2.6%.The success of ERCP is influenced by the technical difficulty. For this reason, the success rate in our center was slightly over 50%, but with few complications.

Pneumatic dilation and surgical myotomy are currently the procedures of choice to treat achalasia. The selection of one or other treatment depends on the experience of each center and patient preferences.To review the experience of pneumatic dilation in patients with achalasia in our center.We included all patients with a clinical, endoscopic and manometric diagnosis compatible with achalasia who underwent pneumatic dilation in a 19-year period. All dilations were routinely performed with a Rigiflex(®) balloon, usually at pressures of 250, 250 and 300mm Hg in three inflations of one minute, each separated by one minute. The success of the dilation was assessed on the basis of the patient's symptoms, the number of sessions, the need for surgery, and the presence of complications.A total of 171 patients were included, 53.2% men and 46.8% women, with a mean age of 51.53±17.78 years (16-87 years), from June 1993 to October 2012. A 35-mm balloon was used in 157 patients, a 30-mm balloon in 9 patients and a 40-mm balloon in 7 patients. A single dilation session was required in 108 patients, two sessions were required in 56 patients, with a mean time between the first and second sessions of 25.23±43.25 months (1-215 months), and 3 sessions were required in 7 patients with a mean time between the second and third sessions of 6.86±5.33 months (1-15 months). Outcome after dilation was successful in 81% of the patients. Of the 140 responders, 121 had complete response (complete disappearance of symptoms without recurrence) and 19 partial response (initial disappearance of symptoms with subsequent reappearance). Surgery (Heller myotomy) was required in 15.8% of the patients. Perforation occurred in 4 of the 171 patients as a complication of the technique; these perforations were satisfactorily resolved, two by conservative treatment and two by surgery. There was no mortality associated with the technique or its complications.In our series, pneumatic dilation had a high success rate. In most patients, a single session was required and the complications rate was low. These results show that this technique is safe and effective in these patients, avoiding a large number of surgical interventions.

Antecedentes: la causa más común de la estenosis traqueal es la intubación prolongada. El tratamiento definitivo que ofrece los mejores resultados es la plastia traqueal. Objetivo: identificar los factores relacionados con las complicaciones de la anastomosis (reestenosis traqueal, granuloma en el sitio de la plastia y dehiscencia) en pacientes a quienes se realizó plastia traqueal. Material y métodos: estudio observacional, longitudinal, analítico y retrospectivo en el que se revisaron los expedientes de todos los pacientes con diagnóstico de estenosis en la vía aérea postintubación, con tratamiento quirúrgico de plastia traqueal efectuado en el Departamento de Cirugía de Cabeza y Cuello del Hospital de Especialidades, Centro Médico Nacional Siglo XXI, del Instituto Mexicano del Seguro Social, México DF. Se analizaron las variables: edad, sexo, días de intubación, diabetes mellitus, hipertensión arterial, insuficiencia renal crónica, cardiopatía, y tratamiento con anticoagulantes. Se registraron las dilataciones, la traqueostomía, o ambas, efectuadas antes de la plastia traqueal. También se consideraron las maniobras para liberar la laringe, localización y longitud de la estenosis, infección de herida quirúrgica, y hematoma. Se registraron las complicaciones de la anastomosis con un seguimiento mínimo de seis meses. Resultados: se estudiaron 71 pacientes: 25 mujeres (35%) y 46 hombres (65%) con edad promedio de 42 años. El promedio de días de intubación fue de 15 (3-90). Requirieron traqueostomía o dilataciones traqueales previo a la plastia traqueal 23 pacientes (32.3%). Durante el seguimiento doce pacientes (17%) resultaron con reestenosis, cinco con (7%) granuloma, y un paciente (1%) con dehiscencia. El único factor significativo asociado con la complicación de la anastomosis fue la longitud de la estenosis de 3 cm o más (p 0.01). Conclusiones: nuestros hallazgos sugieren que la tensión excesiva y la devascularización en los bordes anastomosados son los factores relacionados con las complicaciones de las anastomosis posteriores a la plastia traqueal.

El presente artículo es resultado de un estudio realizado a los almacenes de cadena de la ciudad de Cartagena para medir el impacto de los programas de aportes y donaciones sobre la imagen corporativa y reputación. Se hace primero un seguimiento de la discusión teórica reciente alrededor de los conceptos de RSE, aportes y donaciones, imagen corporativa y reputación. Luego se aplica un método cuantitativo y se formulan cuatro hipótesis para medir la incidencia de las variables acción social y relaciones con la comunidad sobre la imagen corporativa y reputación. La discusión teórica encontró que la RSE debe entenderse como una filosofía de gestión empresarial comprometida con el mejoramiento de las condiciones de vida de la sociedad en general. Adicionalmente, las pruebas de hipótesis confirmaron las diferencias conceptuales entre la imagen corporativa y reputación por encontrarse una relación directa y positiva entre las variables acción social y relaciones con la comunidad sobre la imagen corporativa y una relación no directa entre las variables acción social y reputación. Esto muestra que los programas de aportes y donaciones pueden contribuir a mejorar la imagen corporativa, mientras que la reputación exige un esfuerzo más integral y de acciones a lo largo del tiempo.

This study investigates the mutagenicity of nifurtimox (NFX) and eight analogues in Salmonella typhimurium indicator strains that possess different levels of classical nitroreductase or O-acetyltransferase activities. The NFX analogues tested replace the 3-methyl-4-yl-tetrahydro-1,4-thiazine-1,1-dioxide group of the parent compound with the following other groups: indazol-1-yl (1G); pyrazol-1-yl (1B); benzimidazol-1-yl (1E); 1,2,4-triazol-4-yl (1D); 1-methyl-3-methylthio-1,2,4-triazol-4-yl-5-thione (1I); 3,5-bis(methylthio)-1,2,4-triazol-4-yl (1H); 1-adamantyl (ADA); and 4,6-diphenylpyridin-1-yl-2-one (1K). In the genetic backgrounds of the standard Ames tester strains TA98 and TA100, these bacteria combine the L-arabinose resistance forward mutation assay (Ara test) with a deficiency or overproduction of either nitroreduction or O-acetylation. The Ara test revealed, in agreement with previous findings, important differences between TA98 and TA100 and demonstrated, moreover, that these genetic differences are of significance in mutagenicity testing with nitrofuran compounds. The Ara test also indicated dissimilarities between the metabolic activation of NFX and its analogues, these compounds being classified in three different groups according to their mutagenicity toward strain BA14 (genetic background of TA98) and its derivatives. The first group included analogues (1G, 1E, 1I, and ADA) that showed similar mutagenic potency in all bacterial strains. These compounds are considered not to be substrates for both classical nitroreductase and O-acetyltransferase. The second group included compounds (analogues 1B and 1K, and the reference drug NFX) with increased mutagenicity toward the strain overproducing the classical nitroreductase, and/or reduced mutagenicity toward the corresponding deficient bacteria. These compounds are considered to be activated by the classical nitroreductase. The third group (analogues 1D and 1H) was activated by bacterial O-acetyltransferase, and consequently showed increased and decreased mutagenicity with the particular overproducer or deficient bacterial strain, as compared to their isogenic parentals. Previous reports have pointed out interest in NFX analogue 1H as a promising candidate for the replacement of NFX. The present study further enhances the putative interest of compound 1H, based on the different metabolic activation pathway exhibited by this analogue as compared to the parental drug, NFX.

Evaluation of patients with acute gastrointestinal bleeding (AGB) requires early clinical evaluation and analysis. The aim of this study is to evaluate early concordance of hemoglobin (Hb) and hematocrit (HTC) levels determined by conventional venous blood gas analysis (VBG) and by conventional Laboratory in Emergencies (LAB).Observational and prospective study of patients admitted in the Gastrointestinal Haemorrhage Unit with both high and low AGB. Demographic and clinical variables and simultaneous venous blood samples were obtained to determine Hb and HTC by VBG and LAB. Concordance in both methods was analysed by intra-class correlation coefficient (ICC) and Bland-Altman analysis.One hundred and thirty-two patients were included: 87 (65.9%) males, average age 66.8 years. VBG overestimated Hb in 0.49 g/dl (95% confidence interval: 0.21-0.76) with respect to LAB. Concordance was very high in Hb (ICC 0.931) and high in HTC (0.899), with the Bland-Altman graphs showing both concordance and overestimation of Hb levels determined by VBG. In 19 patients (14.39%), Hb by VBG exceeded in more than 1g/dL the final determination obtained by LAB.Early determination of Hb and HTC in patients with AGB by VBG provides reliable results in the initial evaluation of anaemia. VBG systematically overestimates Hb values by less than 0.5 g/dl, and therefore clinical and hemodynamic evaluation of the bleeding patient should prevail over analytical results.

The induction of forward mutations to L-arabinose resistance (AraR) and of reversions to histidine prototrophy (His+) can be quantitatively compared in Salmonella typhimurium BA strains. The BA bacteria carry the araD531 allele required for the Ara assay and a his auxotrophy (hisD3052 or hisG46) required for the His assay. In this study, 2 new sets of BA indicator strains have been constructed in order to combine the Ara forward and the His reverse mutation assays of S. typhimurium with deficiency, or over-production, in either classical nitroreductase or O-acetyltransferase for mutagenicity testing of nitro-containing chemicals. Nine mutagens with different chemical structures were tested to compare the specific mutagenic sensitivities of the new constructions with those of the parental and of the conventional TA indicator bacteria. The Ara test, which responded with high sensitivity to all chemicals tested, revealed important differences between the standard tester strains TA98 and TA100 with respect to the activation of mutagens considered to be dependent on classical nitroreductase activity. Total correspondence was found between the specific mutagenic sensitivities of the defective and the overproducing bacteria in the genetic background of TA98 but not in that of TA100. In the genetic background of TA100, chemicals such as nitrofurantoin and nitrofurazone displayed 10-fold reduced mutagenicity to the "classical nitroreductase" defective strain without increasing mutagenicity to the corresponding overproducing bacteria. This discrepancy might be attributed to the greater nitroreduction capability of strain TA100 (68.12 nmole/min/mg protein) as compared to TA98 (24.42 nmole/min/mg protein), by assuming that nitrofurantoin and nitrofurazone are such good substrates for classical nitroreductase that the additional enzyme activity produced from the corresponding overexpressing plasmid when present in TA100 no longer affected their metabolic activation. We propose that the Ara forward mutation test carried out in the set of over-producing bacteria constructed in the genetic background of TA98 might play a role for routine testing of large number of samples. The isogenic defective strains could be used in cases of uncertain results with the corresponding over-producing bacteria. Finally, the reversion of the his alleles accompanying the Ara assay in the BA strains could play a role in assessing the presence of mixtures of chemicals with different mutagenic specificity in samples of environmental relevance such as urban air, foods, and water.

Eosinophilic esophagitis is an underdiagnosed disease that should be suspected in all patients with dysphagia and food impaction. Although these are the leading symptoms, the clinical and endoscopic spectrum is highly varied. Clinicians should be aware of the risk of endoscopy-related complications in this disorder. Precautions should be maximized in endoscopic examinations to avoid iatrogenic damage. We describe the case of a young patient with esophageal stricture and dysphagia who suffered a perforation following a biopsy.

Ischemic gastropathy is highly infrequent in daily medical practice. In the last few years, the number of reported cases has increased. Although the guiding symptom is usually abdominal pain, the clinical spectrum of the disease is highly variable. Early diagnosis and treatment are essential to change the natural history of the disease. We present the case of a 75-year-old man with chronic abdominal pain who developed a fulminant form of necrotizing gastric ischemia and died within less than 24h.

Ten patients with advanced Parkinson's disease, presenting with tremor, rigidity and akinesia had autologous adrenal medullary transplantation taken from the left adrenal gland to the head of the right caudate nucleus. Particular attention was taken to avoid prolonged exposure of the adrenal tissue before transplantation and to separate the medullary from the cortical adrenal tissues. Postoperative CT scans confirmed the correct position of the transplants. Differences between pre- and 1-year postoperative clinical conditions were statistically evaluated, with patients under medical (L-dopa) treatment and after the medication was temporarily discontinued. Performance of motor tasks was tested to differentiate slowness of movements imposed by excessive muscular tension (rigidity) from that secondary to delayed reaction time to sensory demands (akinesia). Two deaths occurred 35 and 69 day after surgery for causes not related to the surgical procedures. One of those patients had remained stable neurologically and the other had deteriorated to progressive dementia and catatonia. At autopsy, no lesions in the CNS other than those expected from the surgical procedure were evident, and histological examination failed to reveal chromaffin cells in the head of the right caudate nucleus. Evaluation of the 8 cases that survived for 1 year revealed no significant improvement in their clinical or motor task performance, when considered as a group. However, cases with mild akinesia did better than cases with moderate to advanced akinesia, suggesting that transplantation is indicated in cases with rigidity, but not in cases with 'negative' symptoms of Parkinson's disease. All cases required postoperative medication.