Immune changes over time and survival in patients with cirrhosis treated with non-selective beta-blockers: A prospective longitudinal study.

BACKGROUND: Treatment with non-selective beta-blockers (NSBB) has been associated with anti-inflammatory and anti-cancer effects in patients with cirrhosis. This study aims to analyze the impact of chronic NSBB treatment on immune activation and disease progression in stable outpatients with cirrhosis. METHODS: In this prospective follow-up of 150 patients with cirrhosis, 39 received treatment with NSBB. Blood samples were taken every 6-9 months, and immune and adrenergic variables were measured. Mixed linear models were used to assess the effect of NSBB on these variables over time. Multivariate Cox regression was used to study associations with adverse clinical events (hepatocellular carcinoma, death, or liver transplant). RESULTS: Median follow-up was 1635 days. NSBB treatment was associated with significantly lower levels of IL-6 (ß - 4.7; 95% confidence interval [CI] -6.9, -2.6) throughout the study. During follow-up, 11 patients developed hepatocellular carcinoma, 32 died, and 4 underwent liver transplant. Patients with higher concentrations of IL-10, IL-6 and IFN-γ developed more clinical events. Event-free survival was significantly better in patients treated with NSBB (hazard ratio 0.36, 95% CI 0.18, 0.71) in a multivariate Cox regression adjusted for Child-Pugh-Score, esophageal varices, and platelets. CONCLUSION: Chronic treatment with NSBB in patients with stable cirrhosis gives rise to a different state of immune activation, characterized by lower concentrations of IL-6 over time, and it is associated with a reduced risk of adverse event (death, hepatocellular carcinoma, or transplant), after controlling for disease severity.

Iron Trichloride-Mediated Cascade Reaction of Aminosugar Derivatives for the Synthesis of Fused Tetrahydroisoquinoline-Tetrahydrofuran Systems.

A method to obtain tetrahydroisoquinolines (THIQs) fused to tetrahydrofuran rings from aminosugar derivatives has been developed. The procedure relies on a key deprotection of benzyl ethers followed by a double-cyclization sequence, using FeCl3 as the sole reagent. This tandem reaction affords the construction of novel fused polycyclic heterocycles with total stereochemical control.

Enhanced recovery after low- and medium-risk liver transplantation. A single-center prospective observational cohort study.

BACKGROUND & AIMS: Few studies have fully applied an enhanced recovery after surgery (ERAS) protocol to liver transplantation (LT). Our aim was to assess the effects of a comprehensive ERAS protocol in our cohort of low- and medium-risk LT patients. METHODS: The ERAS protocol included pre-, intra-, and post-operative steps. During the five-year study period, 181 LT were performed in our institution. Two cohorts were identified: low risk patients (n = 101) had a laboratory model for end-stage liver disease (MELD) score of 20 points or less at the time of LT, received a liver from a donor after brain death, and had a balance of risk score of 9 points or less; medium-risk patients (n = 15) had identical characteristics except for a higher MELD score (21-30 points). In addition, we analyzed the remaining patients (n = 65) who were transplanted over the same study period separately using the ERAS protocol. RESULTS: The low-risk cohort showed a low need for packed red blood cells transfusion (median: 0 units) and renal replacement therapy (1%), as well as a short length of stay both in the intensive care unit (13 h) and in the hospital (4 days); morbidity during one-year follow-up, and probability of surviving to one year (89.30%) and five years (76.99%) were in line with well-established reference data. Similar findings were observed in the medium-risk cohort. CONCLUSIONS: This single-center prospective observational cohort study provides evidence that ERAS is feasible and safe for low- and medium-risk LT.

Bacterial DNA translocation contributes to systemic inflammation and to minor changes in the clinical outcome of liver transplantation.

Bacterial (bact)DNA is an immunogenic product that frequently translocates into the blood in cirrhosis. We evaluated bactDNA clearance in patients undergoing liver transplantation (LT) and its association with inflammation and clinically relevant complications. We prospectively included patients consecutively admitted for LT in a one-year follow-up study. We evaluated bactDNA before and during the first month after LT, quantifying cytokine response at 30 days. One hundred patients were included. BactDNA was present in the blood of twenty-six patients undergoing LT. Twenty-four of these showed bactDNA in the portal vein, matching peripheral blood-identified bactDNA in 18 cases. Thirty-four patients showed bactDNA in blood during the first month after LT. Median TNF-α and IL-6 levels one month after LT were significantly increased in patients with versus without bactDNA. Serum TNF-α at baseline was an independent risk factor for bactDNA translocation during the first month after LT in the multivariate analysis (Odds ratio (OR) 1.14 [1.04 to 1.29], P = 0.015). One-year readmission was independently associated with the presence of bactDNA during the first month after LT (Hazard ratio (HR) 2.75 [1.39 to 5.45], P = 0.004). The presence of bactDNA in the blood of LT recipients was not shown to have any impact on complications such as death, graft rejection, bacterial or CMV infections. The rate of bactDNA translocation persists during the first month after LT and contributes to sustained inflammation. This is associated with an increased rate of readmissions in the one-year clinical outcome after LT.

Treatment with non-selective beta-blockers affects the systemic inflammatory response to bacterial DNA in patients with cirrhosis.

BACKGROUND & AIMS: The use of non-selective beta-blockers has been associated with lower rates of infection and reduced infection-associated morbidity in patients with cirrhosis. However, it is unknown if these drugs modify the systemic inflammatory response to circulating bacterial DNA. METHODS: Sixty-three patients with cirrhosis were included during an episode of decompensation by ascites. Thirty of those patients were on beta-blockers. Blood samples were obtained after each patient had been in the supine position for at least 30 minutes in a quiet atmosphere. Bacterial DNA, serum cytokines, nitric oxide, and LPS were determined. Phagocytic and oxidative burst activities were determined in polymorphonuclear cells from the patients. RESULTS: The detection rate of bacterial DNA in the blood was the same (33%) for patients not treated and treated with non-selective beta-blockers. Patients naive to non-selective beta-blockers showed significantly higher serum levels of IL6, IFN-gamma and IL10 in response to the presence of bacterial DNA. Patients treated with non-selective beta-blockers showed higher basal inflammatory activity that did not change with the presence of bacterial DNA. Monocytes and granulocytes from patients treated with non-selective beta-blockers showed a significantly increased phagocytic capacity in the presence of bacterial DNA. CONCLUSIONS: In patients with cirrhosis, chronic treatment with beta-blockers is associated with a higher unstimulated production of serum cytokines and an increased phagocytic activity in the presence of bacterial DNA.

ß2­adrenergic receptor functionality and genotype in two different models of chronic inflammatory disease: Liver cirrhosis and osteoarthritis.

The present study was designed to investigate the functional status of ß2 adrenoceptors (ß2AR) in two models of chronic inflammatory disease: liver cirrhosis (LC) and osteoarthritis (OA). The ß2AR gene contains three single nucleotide polymorphisms at amino acid positions 16, 27 and 164. The aim of the present study was to investigate the potential influence of lymphocyte ß2AR receptor functionality and genotype in LC and OA patients. Blood samples from cirrhotic patients (n=52, hepatic venous pressure gradient 13±4 mmHg, CHILD 7±2 and MELD 11±4 scores), OA patients (n=30, 84% Kellgren­Lawrence severity 4 grade, 14% knee replacement joint) and healthy volunteers as control group (n=26) were analyzed. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood and basal and isoproterenol induced adenylate cyclase activity (isoproterenol stimulus from 10­9 to 10­4 mM), and ß2AR allelic variants (rs1042713, rs1042714, rs1800888) were determined. ß2AR functionality was decreased in the two different models of chronic inflammatory disease studied, OA (50% vs. control) and LC (85% vs. control). In these patients, the strength of the ß2AR response to adrenergic stimulation was very limited. Adrenergic modulation of PBMC function through the ß2AR stimulus is decreased in chronic inflammatory processes including LC and OA, suggesting that the adrenergic system may be important in the development of these processes.

Clinical and epidemiological characteristics of pyogenic liver abscess in people 65 years or older versus people under 65: a retrospective study.

BACKGROUND: To analyse the clinical, epidemiological, microbiological and prognostic differences of pyogenic liver abscess (PLA) in older (≥ 65 years of age) versus younger patients (< 65 years). METHODS: Multicentre, retrospective cohort study in all patients with PLA admitted to two Spanish hospitals from January 2000 to January 2014. Cases were divided into two age groups (< 65 years and ≥65 years) for comparison of clinical, epidemiological and microbiological characteristics as well as treatment. RESULTS: Of 98 patients analysed, 40 patients were younger than 65, and 58 were aged 65 or older. Significant associations in the older group were found with female sex (adjusted odds ratio [ORa] 9.0; 95% CI 1.4, 56), non-cryptogenic origin (ORa 14.5; 95% CI 1.6, 129), absence of chronic liver disease (ORa 14; 95% CI 1.3, 155), Escherichia coli infection (ORa 7.7; 95% CI 1.03, 58), and incidence of complications (ORa 2.3; 95% CI 1.04, 5.4). Mortality was 8.2% overall, although all deaths occurred in the older group (8/58; 13.8%) (p = 0.02). DISCUSSION: Our results are in consonance with other published studies. Older patients with PLA tend to present more anomalies in the biliary tract (Kai et. al, World J Gastroenterol 18: 2948-295, 2012, Rahimian et. al, Clin Infect Dis 39:1654-9, 2004, Seeto, Medicine (Baltimore) 75:99-113, 1996, Kao et.al, Aliment Pharmacol Ther 36:467-76, 2012, Lai et. al, Gastroenterology 146:129-37, 2014), while younger patients are more often male and present more commonly with previous liver disease (especially related to alcohol) and cryptogenic PLA. CONCLUSION: In patients aged 65 or older, PLA was more common in women and in those with a history of biliary disease, and E. coli was the most frequent bacterium. Mortality was also higher in the older group.

Hiperplasia nodular regenerativa hepática asociada a inmunodeficiencia común variable y a otras comorbilidades / Nodular regenerative hyperplasia associated with common variable immunodeficiency and other comorbidities

Fundamento y objetivo: Actualmente no se dispone de muchos datos sobre la evolución de la hiperplasia nodular regenerativa (HNR) asociada o no a enfermedades de base, y en concreto de la asociada a inmunodeficiencia común variable (IDCV). Se presentan 20 casos de HNR y se analizan las diferencias entre los casos asociados a IDCV y los relacionados con otras enfermedades. Métodos: Estudio retrospectivo y descriptivo durante un período de 14 años. Resultados: De los 20 pacientes, 12 eran hombres; la mediana de edad fue de 51 años. La IDCV fue la principal enfermedad asociada con HNR. En los pacientes con IDCV y HNR la hemorragia gastrointestinal fue más común, todos tenían elevación de FA y GGT y ninguno tenía valores de albúmina y bilirrubina alterados comparados con los pacientes sin IDCV. De los pacientes con HNR en seguimiento han fallecido el 50% de los asociados a IDCV (2/4) frente al 33,3% (5/15) sin IDCV. Conclusiones: La HNR en los pacientes con IDCV parece manifestarse más con datos bioquímicos de colestasis anictérica e hipertensión portal y podría asociar una supervivencia menor (AU)

Background and objective: Currently, there are not many data on the evolution of nodular regenerative hyperplasia (NRH) associated or not with underlying diseases and in particular that associated with common variable inmunodeficiency (CVID). Twenty cases of NRH are presented, and the differences between the cases associated with CVID and those related to other diseases are analysed. Methods: Retrospective and descriptive study over a period of 14 years. Results: Twelve out of the 20 patients were men; the median age was 51 years. CVID was the main illness associated with NRH. In patients with CVID and NRH, gastrointestinal haemorrhage was more common, all the patients had high gamma glutamyl transferase and alkaline phosphatase and none had altered albumin and bilirubin levels compared to the patients without CVID. On follow-up, 50% of patients with CVID (2/4) had died compared to 33.3% (5/15) without CVID. Conclusions: NRH in patients with CVID seems to have more biochemical data of anicteric cholestasis and portal hypertension and could be associated with lower survival (AU)

[Nodular regenerative hyperplasia associated with common variable immunodeficiency and other comorbidities]. / Hiperplasia nodular regenerativa hepática asociada a inmunodeficiencia común variable y a otras comorbilidades.

BACKGROUND AND OBJECTIVE: Currently, there are not many data on the evolution of nodular regenerative hyperplasia (NRH) associated or not with underlying diseases and in particular that associated with common variable inmunodeficiency (CVID). Twenty cases of NRH are presented, and the differences between the cases associated with CVID and those related to other diseases are analysed. METHODS: Retrospective and descriptive study over a period of 14 years. RESULTS: Twelve out of the 20 patients were men; the median age was 51 years. CVID was the main illness associated with NRH. In patients with CVID and NRH, gastrointestinal haemorrhage was more common, all the patients had high gamma glutamyl transferase and alkaline phosphatase and none had altered albumin and bilirubin levels compared to the patients without CVID. On follow-up, 50% of patients with CVID (2/4) had died compared to 33.3% (5/15) without CVID. CONCLUSIONS: NRH in patients with CVID seems to have more biochemical data of anicteric cholestasis and portal hypertension and could be associated with lower survival.

Opiniones sobre el proceso asistencial de los pacientes con síndrome de intestino irritable / No disponible

ANTECEDENTES Y PROPÓSITO DEL ESTUDIO: en este estudio se evaluó la experiencia de los pacientes con síndrome de intestino irritable (SII) con el sistema sanitario analizando específicamente las dificultades con las que se encuentran estos pacientes. Métodos: para identificar cuestiones clave se condujeron 3 grupos focales con participación de 19 pacientes y 10 profesionales sanitarios. A partir de estas informaciones se diseñó un guion de preguntas y se realizaron 33 entrevistas estructuradas a pacientes con SII. El estudio de campo se realizó entre noviembre de 2013 y julio de 2014. Finalmente con esta información se diseñó una escala de valoración de la percepción de los pacientes de las atenciones que reciben en atención primaria (14 ítems) y digestivo (13 ítems), analizando validez de constructo y consistencia interna. Resultados: las dificultades de accesibilidad, para resolver dudas, preocupación derivada de la incertidumbre, reducida información sobre pronóstico y sus afectaciones sociales y laborales fueron las más citadas por los pacientes. Bajo cumplimiento y baja persistencia en el plan terapéutico fueron los problemas citados con mayor frecuencia por los profesionales. Los ítems de la escala para atención primaria confluyeron en 4 factores (varianza explicada, 73%), mientras que para digestivo confluyó en 3 factores (varianza explicada, 67%). La consistencia interna fue de 0,84 y 0,82, respectivamente. Un total de 29 (88%) pacientes se manifestaron satisfechos con la atención prestada en digestivo, mientras 24 (73%) se declararon satisfechos con el médico de atención primaria (Chi Cuadrado 2,4, p = 0,21). Conclusiones: este estudio describe los principales problemas asistenciales desde la perspectiva del paciente

BACKGROUND AND PURPOSE OF THE STUDY: This study assessed the experiences of irritable bowel syndrome patients with the healthcare system. Specifically, this study focused on the barriers that patients found

Recomendaciones del Club Español Pancreático para el diagnóstico y tratamiento de la pancreatitis crónica: parte 1 (diagnóstico) / Recommendations of the Spanish pancreatic club on the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis)

La pancreatitis crónica (PC) es una enfermedad relativamente infrecuente, compleja y muy heterogénea. La ausencia de un patrón oro aplicable a las fases iniciales de la PC hace que su diagnóstico precoz sea difícil. Algunas de sus complicaciones, en particular el dolor crónico, pueden ser difíciles de manejar. Hay mucha variedad en el diagnóstico y tratamiento de la PC y de sus complicaciones entre los diferentes centros y profesionales. El Club Español Pancreático ha desarrollado un consenso sobre el manejo de la PC. Dos coordinadores eligieron un panel multidisciplinario de 24 expertos en esta enfermedad. Se elaboró una lista de preguntas. Cada pregunta fue revisada por 2 expertos. Con ello se elaboró un borrador compartido con todo el panel de expertos y discutido en una reunión presencial. En la primera parte del consenso se aborda el diagnóstico de la PC y de sus complicaciones (AU)

Chronic pancreatitis (CP) is a relatively uncommon, complex and highly heterogeneous disease. There is no clear pattern applicable to the initial stages of CP, which hampers its early diagnosis. Some of the complications of CP, especially chronic pain, can be difficult to manage. There is wide variation in the diagnosis and treatment of CP and its complications among centers and health professionals. The Spanish Pancreatic Club has developed a consensus document on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts in this disease. A list of questions was drawn up. Each question was reviewed by two experts. These questions were then used to produce a draft, which was discussed in a face-to-face meeting with all the participants. The first part of the consensus document focusses on the diagnosis of CP and its complications (AU)

[Recommendations of the Spanish Pancreatic Club on the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis)]. / Recomendaciones del Club Español Pancreático para el diagnóstico y tratamiento de la pancreatitis crónica: parte 1 (diagnóstico).

Chronic pancreatitis (CP) is a relatively uncommon, complex and highly heterogeneous disease. There is no clear pattern applicable to the initial stages of CP, which hampers its early diagnosis. Some of the complications of CP, especially chronic pain, can be difficult to manage. There is wide variation in the diagnosis and treatment of CP and its complications among centers and health professionals. The Spanish Pancreatic Club has developed a consensus document on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts in this disease. A list of questions was drawn up. Each question was reviewed by two experts. These questions were then used to produce a draft, which was discussed in a face-to-face meeting with all the participants. The first part of the consensus document focusses on the diagnosis of CP and its complications.

Comparison of the conformational properties of carbasugars and glycosides: the role of the endocyclic oxygen.

A series of carbasugars were prepared and their conformational properties studied by means of NMR spectroscopy. The results were compared to those previously found for O-, S-, and C-ß-glycoside analogs. While the rotational populations of the hydroxymethyl group in O-, S-, and C-glycosides are known to depend on the structural nature of their aglycon, in carbasugars it proved to be independent of the pseudo-aglycon. This result confirms that endocyclic oxygen is necessary for the observed relationship between the structure of the aglycon and the rotational populations of the hydroxymethyl group, and indicates that the stereoelectronic exo-anomeric effect is mainly responsible for such conformational dependence.

Chronic hepatitis C virus infection and associated liver disease among the inmates of a Spanish prison

Objetivos el objetivo de este estudio fue determinar la prevalencia de la infección crónica por el virus de la hepatitis C (VHC) y sus genotipos en una población penitenciaria, así como también describir los hallazgos histológicos encontrados en una subpoblación de sujetos a los que se les realizó biopsia hepática y en los que se identificaron los posibles factores de riesgo asociados a la fibrosis y a la actividad inflamatoria. Métodos se seleccionaron 800 internos, de los cuales 730 aceptaron el cribado con serología del VHC y confirmación por PCR (polymerase chain reaction 'reacción en cadena de la polimerasa'). Se estudiaron las variables sociodemográficas, conductuales y relacionadas con la encarcelación. A los sujetos con infección crónica por VHC se les ofreció la realización de una biopsia hepática. Se definió enfermedad hepática avanzada como fibrosis (..) (AU)

Objective: The objective of this study was to determine the prevalence and genotype distribution of chronic hepatitis C virus (HCV) infection in a penitentiary population. The secondary objective was to describe histological findings in liver of the biopsied population, and identify risk factors associated with liver fibrosis and inflammatory activity. Methods: Among 800 inmates, 730 accepted HCV antibody screening and PCR confirmation. Sociodemographic, behavioral, and incarceration-related variables were analyzed. Liver biopsy was offered to individuals with chronic HCV infection. Advanced liver disease was defined as fibrosis ¡Ý3 and/or an inflammatory activity index score ¡Ý8).Results: HCV antibodies were found in 279 inmates. PCR confirmed HCV infection in 250 inmates, yielding a prevalence of 34.2% (95% confidence interval [CI]: 30.8¨C37.8). Intravenous drug use was independently associated with HCV infection, odds ratio (OR) 51.7 (95% CI: 31¨C86). Genotypes were 1a 32.9%, 3 29.7%, 1b 18.4% and 4 17.1%. Fifty-one liver biopsies were performed; advanced liver disease was found in 7 patients (13.7%) based on fibrosis and in 31 patients (60.7%) based on the inflammatory activity index. High AST and ALT levels were associated with advanced liver disease established on both fibrosis and inflammatory activity (P<.05). Lengthy intravenous drug use was associated with inflammatory activity (P=.02; OR 1.2; 95% CI: 1.03¨C1.7).Conclusions: Persistent HCV infection is highly prevalent among prison inmates and is associated with intravenous drug abuse. HCV genotype diversity is higher in prison inmates than in the general population. Higher transaminase levels are associated with advanced liver disease (AU)

[Chronic hepatitis C virus infection and associated liver disease among the inmates of a Spanish prison]. / Infección crónica por el virus de la hepatitis C y enfermedad hepática asociada en una prisión española.

OBJECTIVE: The objective of this study was to determine the prevalence and genotype distribution of chronic hepatitis C virus (HCV) infection in a penitentiary population. The secondary objective was to describe histological findings in liver of the biopsied population, and identify risk factors associated with liver fibrosis and inflammatory activity. METHODS: Among 800 inmates, 730 accepted HCV antibody screening and PCR confirmation. Sociodemographic, behavioral, and incarceration-related variables were analyzed. Liver biopsy was offered to individuals with chronic HCV infection. Advanced liver disease was defined as fibrosis 3 and/or an inflammatory activity index score 8). RESULTS: HCV antibodies were found in 279 inmates. PCR confirmed HCV infection in 250 inmates, yielding a prevalence of 34.2% (95% confidence interval [CI]: 30.8-37.8). Intravenous drug use was independently associated with HCV infection, odds ratio (OR) 51.7 (95% CI: 31-86). Genotypes were 1a 32.9%, 3 29.7%, 1b 18.4% and 4 17.1%. Fifty-one liver biopsies were performed; advanced liver disease was found in 7 patients (13.7%) based on fibrosis and in 31 patients (60.7%) based on the inflammatory activity index. High AST and ALT levels were associated with advanced liver disease established on both fibrosis and inflammatory activity (P<.05). Lengthy intravenous drug use was associated with inflammatory activity (P=.02; OR 1.2; 95% CI: 1.03-1.7). CONCLUSIONS: Persistent HCV infection is highly prevalent among prison inmates and is associated with intravenous drug abuse. HCV genotype diversity is higher in prison inmates than in the general population. Higher transaminase levels are associated with advanced liver disease.

Serum and ascitic fluid bacterial DNA: a new independent prognostic factor in noninfected patients with cirrhosis.

UNLABELLED: We tested the hypothesis that the presence of bacterial DNA (bactDNA) in ascitic fluid and serum is associated with decreased survival in patients with cirrhosis. In a prospective, multicenter study, we analyzed the clinical evolution of 156 patients with cirrhosis and ascites (first or recurrence) with lower than 250 polymorphonuclear cells (PMN)/muL, negative ascites bacteriological culture, and absence of other bacterial infections being admitted for evaluation of large-volume paracentesis, according to the presence of bactDNA at admission. Survival, causes of death, and successive hospital admissions were determined during a 12-month follow-up period. BactDNA was detected in 48 patients. The most prevalent identified bactDNA corresponded to Escherichia coli (n = 32/48 patients, 66.6%). Patients were followed for 12 months after inclusion and in this period 34 patients died: 16 of 108 (15%) bactDNA negative versus 18 of 48 (38%) bactDNA positive (P = 0.003). The most frequent cause of death was acute-on-chronic liver failure in both groups (7/16 and 9/18 in patients without or with bactDNA, respectively), although more prevalent in the first month of follow-up in patients with presence of bactDNA (0 versus 4/7). When considering patients with model for end-stage liver disease (MELD) score less than 15, mortality was significantly higher in those with presence of bactDNA. Spontaneous bacterial peritonitis developed similarly in patients with or without bactDNA at admission. CONCLUSION: The presence of bactDNA in a patient with cirrhosis during an ascitic episode is an indicator of poor prognosis. This fact may be related to the development of acute-on-chronic liver failure at short term and does not predict the development of spontaneous bacterial peritonitis.

Clinical significance of extrapyramidal signs in patients with cirrhosis.

BACKGROUND/AIMS: Extrapyramidal signs have been described in cirrhosis and there is little information about their clinical significance. The aims of this study have been to investigate the relationship between extrapyramidal signs and cognitive impairment, and what is their influence on quality of life. METHODS: 46 patients with cirrhosis were evaluated for cognitive impairment with psychometric tests (Trail-Making Test part A, Grooved-Pegboard, Block-Design, Oral Symbol Digit and Stroop Test) and cognitive evoked potentials (P300). Extrapyramidal signs were evaluated using the UPDRS scale. Health-related quality of life (HRQL) was measured using SF-36 scale and the Chronic Liver Disease Questionnaire (CLDQ). RESULTS: Twenty-two patients had extrapyramidal signs, and these patients scored worse in all psychometric tests, except Block-Design. Patients with extrapyramidal signs also showed a longer P300 latency. Moreover, patients with extrapyramidal signs had the worst score in all the HRQL scales used. A multivariate analysis disclosed that the only variable showing an independent relationship to the mental component summary of SF-36 and with CLDQ was UPDRS score. CONCLUSIONS: We have found a clear relationship between the presence of extrapyramidal signs and cognitive impairment. Moreover, patients with extrapyramidal signs have worse scores in quality of life scales.

A sequential study of serum bacterial DNA in patients with advanced cirrhosis and ascites.

Bacterial translocation is currently considered the main pathogenic mechanism leading to spontaneous bacterial peritonitis in patients with advanced cirrhosis and ascites. However, to the authors' knowledge there is no information regarding the characteristics of this process in humans. The goals of the current study were to pursue partially identified bacterial DNA in blood (what the authors consider molecular evidence of bacterial translocation) through its relative quantification in a 72-hour study period by using real-time polymerase chain reaction (PCR). A consecutive series of 17 patients with advanced cirrhosis and culture-negative, nonneutrocytic ascites were studied. Therapeutic paracentesis was performed at the time of admission, and blood samples were obtained at baseline and every 8 hours in a 3-day period. Bacterial DNA was detected by a PCR-based method, relatively quantified by real-time PCR, and identified by automated nucleotide sequencing. Seven of 17 patients demonstrated the simultaneous presence of bacterial DNA in blood and ascitic fluid at the time of admission. After therapeutic paracentesis was performed, bacterial DNA persisted in the blood for a minimum of 24 hours, and was reported to last as long as 72 hours in some patients. In addition, different patterns of bacterial DNA appearance and clearance from the blood were identified. The nucleotide sequencing process demonstrated that bacteria detected in the first sample were identical to those noted in subsequent detections over time. In conclusion, bacterial translocation is a single-species, dynamic process that appears to develop in a subgroup of patients with advanced cirrhosis.

Intestinal permeability is increased in patients with advanced cirrhosis.

BACKGROUND/AIMS: The dysfunction of the intestinal barrier is a factor that has been related to bacterial translocation from lumen to extra-intestinal sites and consequently to the development of spontaneous bacterial peritonitis. The aim of this study was to investigate if the alterations of the intestinal barrier in cirrhosis are related with the degree of liver failure and associated with other clinical complications. METHODOLOGY: Intestinal permeability was assessed by means of the lactulose/mannitol test in 79 cirrhotic and 25 controls subjects. They received 10 g of lactulose and 5 g of mannitol. Lactulose and mannitol were measured in a five-hour urinary volume. RESULTS: Lactulose/mannitol ratio was significantly higher in cirrhotic patients than in controls (p = 0.03). This was more evident in end-stage cirrhosis. Patients with ascites, or encephalopathy showed a statistically significant increase in lactulose/mannitol ratio when compared to patients without these complications. CONCLUSIONS: The increased intestinal permeability is related to the progression of the liver disease and is more relevant with overt clinical complications. This is due to an increased absorption of lactulose. However, as liver disease progresses, mannitol absorption is progressively reduced, probably due to a reduced surface of absorption, and these events are more relevant in patients with overt clinical complications.

Stereoselective synthesis of cyclic ethers by intramolecular trapping of dicobalt hexacarbonyl-stabilized propargylic cations.

The intramolecular attack of a hydroxy group on an exo-biscobalthexacarbonyl propargylic cation provides cyclic ethers with six- to nine-membered rings. The scope and limitations of the methodology are described. The reaction is stereoselective when additional stereocenters are present, providing iterative methodology to access ladder-like cyclic ethers.