Biomedical subjects

Juan Rodés

Publications and source records attributed to Juan Rodés.

67 records · Page 4Linked to original sources

PubMed2002

Failure of Lactobacillus spp. to prevent bacterial translocation in a rat model of experimental cirrhosis.

BACKGROUND/AIMS: Prophylaxis of spontaneous bacterial peritonitis in cirrhotic patients with norfloxacin is associated with emergence of quinolone-resistant Enterobacteriaceae. We investigated whether an alternative strategy with Lactobacillus prevents bacterial translocation and ascitic fluid infection in cirrhotic rats. METHODS: CCl(4)-induced cirrhotic rats with ascites (n=34) were allocated to treatment with oral Lactobacillus strain GG at 1-2 x 10(9) cfu/day for 8-10 days (group LGG) or milk (group MILK). In addition, 20 cirrhotic rats were given a single dose of 15 mg norfloxacin orally and then allocated to Lactobacillus (group NOR-LGG) or milk (group NOR-MILK). Ten healthy rats served as control. After sacrifice the cecal flora were analyzed and the prevalence of bacterial translocation and ascitic fluid infection assessed. RESULTS: Cecal colonization with Lactobacillus was achieved in 90% of treated rats. The prevalence of bacterial translocation to mesenteric lymph nodes was 10% in control rats and 93, 84, 70 and 100% in groups MILK, LGG, NOR-MILK and NOR-LGG, respectively (P>0.1 for comparison of treatment groups), the prevalence of ascitic fluid infection was 60, 32, 40 and 40% (P>0.1). Bacterial translocation of Lactobacillus was observed in 24% of rats treated. CONCLUSION: Lactobacilli fail to prevent bacterial translocation and ascitic fluid infection in experimental cirrhosis in spite of successful intestinal colonization.

Animals↗

PubMed2002

Daily norfloxacin is more effective than weekly rufloxacin in prevention of spontaneous bacterial peritonitis recurrence.

Our aim was to compare weekly rufloxacin with daily norfloxacin in the secondary prophylaxis of spontaneous bacterial peritonitis and to examine changes in antibiotic susceptibility in fecal Escherichia coli. The method used was an open randomized clinical trial including 79 patients who received either norfloxacin 400 mg/day or rufloxacin 400 mg/week and followed up for one year. E. coli counts, quinolone susceptibility, and drug concentrations in feces were investigated in 12 patients. Cumulative one-year probability of peritonitis recurrence was 26% for patients on norfloxacin and 36% for those on rufloxacin (P = 0.16). Norfloxacin was more effective in the prevention of peritonitis recurrence due to Enterobacteriaceae (0% vs 22%, P = .01). At the end of follow-up, all 12 patients had E. coli resistant to quinolones in their feces. In conclusion, weekly rufloxacin is not an alternative to daily norfloxacin in the prevention of peritonitis recurrence. The development of quinolone-resistant E. coli in feces may be an important problem in patients on long-term quinolone prophylaxis.

Aged↗

PubMed2002

Expected developments in hepatology.

It is very difficult to predict new developments in hepatology so we have decided to analyse the most important issues related to three clinical conditions in hepatology. The first is chronic hepatitis. Here, we discuss the relevance of occult forms of hepatitis B virus infection in the development of cryptogenic liver disease and hepatocellular carcinoma. In addition, the role of genotyping in hepatitis B is analysed, indicating that patients with genotype A have a better prognosis than those with genotype D. The treatment of hepatitis B virus infection is also reviewed, and it has been suggested that research should be directed towards the development of new anti-viral agents to suppress virus replication. The natural history of hepatitis C virus infection is considered, emphasizing the need to know the progression of fibrosis in these patients. The chapter also suggests that treatment of hepatitis C virus infection with pegilated interferon and ribavirin is currently relatively effective. New therapeutic strategies will be required in the future, the most important challenge being the development of a hepatitis C virus vaccine. The second section is on chronic cholestasis. The role of anti-mitochondrial antibodies in primary biliary cirrhosis is considered. The possible infectious agents implicated as potential triggers of primary biliary cirrhosis are also discussed, suggesting that several infections may play a role in the pathogenesis of this condition. Other aetiopathogenic factors, for example organic compounds, drugs and chemicals, are indicated. It is possible that, in the near future, the precise sequence and molecular basis by which infectious agents or xenobiotics may initiate the cascade of the autoimmune response will be defined. One of the most important challenges in primary sclerosing cholangitis concerns the mechanisms that may induce the development of this disease. Up until now, genetic factors have been suggested, recent data reporting a clear-cut association between primary sclerosing cholangitis and the tumour necrosis factor-alpha(2) allele. The third part of this chapter includes recent progress achieved in hepatocellular carcinoma, discussing developments in the knowledge of hepatocellular carcinogenesis. Hepatocellular carcinomas appear so far to be genetically heterogeneous neoplasms, and this heterogeneity may correlate with the variety of aetiological factors involved. The risk factors and primary, secondary and tertiary prevention of the condition are also analysed. Finally, the development of new therapeutic strategies for hepatocellular carcinoma is evaluated by evidence-based studies.

Antiviral Agents↗

PubMed2002

Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat.

BACKGROUND & AIMS: Recent studies have described the existence of endogenous cannabinoids with vasodilator activity because of their interaction with peripheral CB1 receptors, anandamide being the most extensively investigated. The study investigated whether endogenous cannabinoids are involved in the pathogenesis of the cardiovascular disturbances in experimental cirrhosis. METHODS: Arterial pressure, cardiac output, and total peripheral resistance were measured before and after the administration of a cannabinoid CB1 receptor antagonist to cirrhotic rats with ascites and to control rats. Blood pressure was also assessed in normotensive recipient rats after the intravenous administration of blood cells or isolated monocytes obtained from cirrhotic and control rats. Moreover, the endogenous content of anandamide was measured in circulating monocytes of cirrhotic and control rats by gas chromatography/mass spectrometry. RESULTS: CB1 receptor blockade did not modify systemic hemodynamics in control rats, but significantly increased arterial pressure and peripheral resistance in cirrhotic animals. Blood cell suspension or monocytes from cirrhotic animals, but not from controls, induced arterial hypotension in recipient rats. Finally, anandamide was solely detected in monocytes of cirrhotic animals. CONCLUSIONS: Monocytes of cirrhotic rats with ascites are activated to produce anandamide and this substance contributes to arterial hypotension in experimental cirrhosis.

Animals↗

PubMed2002

5-lipoxygenase inhibition reduces intrahepatic vascular resistance of cirrhotic rat livers: a possible role of cysteinyl-leukotrienes.

BACKGROUND & AIMS: Cysteinyl-leukotrienes (Cys-LTs) increase intrahepatic vascular resistance in normal rat livers. CCl4 cirrhotic rat livers have increased Cys-LT production and 5-lipoxygenase messenger RNA (mRNA) expression. The aim of this study was to investigate the role of 5-lipoxygenase-derived eicosanoids regulating intrahepatic vascular tone in control and CCl4-induced cirrhotic rat livers. METHODS: In different groups of portally perfused control and cirrhotic rat livers, the following were analyzed: a portal perfusion pressure (PP) dose-response curve to LTD4; the effects on PP caused by either vehicle, the selective 5-lipoxygenase inhibitor AA-861, the selective Cys-LT1 receptor antagonist MK-571, or the dual Cys-LT1 and Cys-LT2 receptor antagonist BAY u9773; and immunohistochemistry for 5-lipoxygenase in liver sections of cirrhotic and control livers. RESULTS: Cirrhotic livers have a hyperesponse to LTD4. In control livers, AA-861 and MK-571 produced a moderate and similar reduction in PP. In cirrhotic livers, 5-lipoxygenase inhibition produced a marked and significantly greater reduction in PP than in controls. However, no effect on PP was observed after MK-571 or BAY u9773. 5-Lipoxygenase-positive cells were markedly increased in cirrhotic livers. CONCLUSIONS: Our results suggest that 5-lipoxygenase-derived eicosanoids may contribute to the increased intrahepatic vascular resistance of cirrhotic rat livers and therefore the pathogenesis of portal hypertension.

Animals↗

PubMed2002

Influence of hepatitis B virus genotype on the long-term outcome of chronic hepatitis B in western patients.

BACKGROUND & AIMS: The aim of this study was to investigate if the variable outcome of chronic hepatitis B may be related to hepatitis B virus (HBV) genotype. METHODS: The clinical and virologic events observed over prolonged follow-up in 258 Spanish patients with chronic hepatitis B infected with different genotypes of HBV were compared. RESULTS: The prevalence of genotype A, D, and F was 52%, 35%, and 7%, respectively. Concomitant sustained biochemical remission and clearance of HBV DNA occurred at a higher rate in genotype A- than in genotype D- (log-rank, 14.2; P = 0.002) or genotype F-infected patients (log-rank, 4.2; P = 0.03). The rate of hepatitis B surface antigen (HBsAg) clearance was higher in genotype A than in genotype D hepatitis (log-rank, 4.6; P = 0.03). Sustained remission and clearance of HBsAg were associated with infection with genotype A by Cox regression analysis. Seroconversion to antibody to hepatitis B e antigen (anti-HBe) was unrelated to HBV genotype, but the rate of sustained remission after seroconversion was higher in genotype A than in genotype D hepatitis both in patients who seroconverted to anti-HBe during follow-up (log-rank, 4.5; P = 0.03) and in patients with positive anti-HBe at baseline (log-rank, 6.66; P = 0.009). Death related to liver disease was more frequent in genotype F than in genotype A (P = 0.02) or genotype D (P = 0.002) hepatitis. CONCLUSIONS: The long-term outcome of chronic hepatitis B is different in patients infected with HBV genotype A, D, or F.

Adult↗

PubMed2002

Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis.

BACKGROUND & AIMS: The transjugular intrahepatic portosystemic shunt (TIPS) has been shown to be more effective than repeated paracentesis plus albumin in the control of refractory ascites. However, its effect on survival and healthcare costs is still uncertain. METHODS: Seventy patients with cirrhosis and refractory ascites were randomly assigned to TIPS (35 patients) or repeated paracentesis plus intravenous albumin (35 patients). The primary endpoint was survival without liver transplantation. Secondary endpoints were complications of cirrhosis and costs. RESULTS: Twenty patients treated with TIPS and 18 treated with paracentesis died during the study period, whereas 7 patients in each group underwent liver transplantation (mean follow-up 282 +/- 43 vs. 325 +/- 61 days, respectively). The probability of survival without liver transplantation was 41% at 1 year and 26% at 2 years in the TIPS group, as compared with 35% and 30% in the paracentesis group (P = 0.51). In a multivariate analysis, only baseline blood urea nitrogen levels and Child-Pugh score were independently associated with survival. Recurrence of ascites and development of hepatorenal syndrome were lower in the TIPS group compared with the paracentesis group, whereas the frequency of severe hepatic encephalopathy was greater in the TIPS group. The calculated costs were higher in the TIPS group than in the paracentesis group. CONCLUSIONS: In patients with refractory ascites, TIPS lowers the rate of ascites recurrence and the risk of developing hepatorenal syndrome. However, TIPS does not improve survival and is associated with an increased frequency of severe encephalopathy and higher costs compared with repeated paracentesis plus albumin.

Ascites↗

PubMed2002

Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis.

The extensive use of invasive procedures and of long-term norfloxacin prophylaxis in the management of cirrhotic patients may have influenced the epidemiology of bacterial infections in cirrhosis. We conducted a prospective evaluation of all bacterial infections diagnosed in patients with cirrhosis in a Liver Unit between April 1998 and April 2000. A total of 405 patients presented 572 bacterial infections in 507 admissions. Spontaneous bacterial peritonitis was the most frequent infection (138 cases). Gram-positive cocci were responsible for 53% of total bacterial infections in the study, being the main bacteria isolated in nosocomial infections (59%). Patients requiring treatment in an intensive care unit and those submitted to invasive procedures presented a higher rate of infections caused by gram-positive cocci (77% vs. 48%, P <.001 and 58% vs. 40%, P <.02, respectively). Fifty percent of culture-positive spontaneous bacterial peritonitis in patients on long-term norfloxacin administration (n = 93) and 16% in patients not receiving this therapy (n = 414) were caused by quinolone-resistant gram-negative bacilli, P =.01. The rate of culture-positive spontaneous bacterial peritonitis caused by trimethoprim-sulfamethoxazole-resistant gram-negative bacilli was also very high in patients on long-term norfloxacin administration (44% vs. 18%, P =.09). In conclusion, infections caused by gram-positive cocci have markedly increased in cirrhosis. This phenomenon may be related to the current high degree of instrumentation of cirrhotic patients. Quinolone-resistant spontaneous bacterial peritonitis constitutes an emergent problem in patients on long-term norfloxacin prophylaxis, with trimethoprim-sulfamethoxazole not being a valid alternative.

Aged↗

PubMed2002

TIPS is a useful long-term derivative therapy for patients with Budd-Chiari syndrome uncontrolled by medical therapy.

Patients with Budd-Chiari syndrome (BCS) may require treatment with portal decompressive surgery or liver transplantation. Transjugular intrahepatic portosystemic shunt (TIPS) represents a new treatment alternative, but its long-term effect on BCS outcome has not been evaluated. Twenty-one patients with BCS consecutively admitted to our unit were evaluated. The mean follow-up was 4 +/- 3 years. Seven patients had nonprogressive forms and were successfully controlled with medical therapy; 1 case, with a short-length hepatic vein stenosis was successfully treated by angioplasty. All 8 patients are alive and asymptomatic. The remaining 13 patients, had a TIPS because of clinical deterioration (in one of them, because early TIPS thrombosis a successful side-to-side portacaval shunt [SSPCS] was performed) followed by an improvement in clinical condition. However, a patient with fulminant liver failure before TIPS insertion, died 4 months later and another patient with cirrhosis at diagnosis had liver transplantation 2 years later. The remaining 11 patients are alive and free of ascites. In 3 of these patients TIPS is patent after 3, 6, and 12 months. The remaining 8 patients developed late TIPS dysfunction. In two of these cases, after angioplasty and restenting, TIPS is patent after a follow-up of 9 and 80 months. In 5 other patients, recurring TIPS occlusion was not further corrected because no signs of portal hypertension were present. In conclusion, in patients with BCS uncontrolled with medical therapy, TIPS is a highly effective technique that is associated with long-term survival.

Abdominal Pain↗

PubMed2002

Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study.

Vasopressin analogues associated with albumin improve renal function in hepatorenal syndrome (HRS). The current study was aimed at assessing the efficacy of the treatment, predictive factors of response, recurrence of HRS, and survival after therapy. Twenty-one consecutive patients with HRS (16 with type 1 HRS, 5 with type 2 HRS) received terlipressin (0.5-2 mg/4 hours intravenously) until complete response was achieved (serum creatinine level < 1.5 mg/dL) or for 15 days; 13 patients received intravenous albumin together with terlipressin. Twelve of the 21 patients (57%) showed complete response. Albumin administration was the only predictive factor of complete response (77% in patients receiving terlipressin and albumin vs. 25% in those receiving terlipressin alone, P =.03). Treatment with terlipressin and albumin was associated with a remarkable decrease in serum creatinine level, increase in arterial pressure, and suppression of the renin-aldosterone system. By contrast, no significant changes in these parameters were found in patients treated with terlipressin alone. Only 1 patient showed ischemic adverse effects. Recurrence of HRS occurred in 17% of patients with complete response. The occurrence of complete response was associated with an improved survival. In conclusion, terlipressin therapy reverses HRS in a high proportion of patients. Recurrence rate after treatment withdrawal is uncommon. Albumin appears to improve markedly the beneficial effects of terlipressin.

Adult↗

PubMed2002

Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model.

Liver biopsy is required for staging hepatic fibrosis in patients with chronic hepatitis C, but it is an expensive procedure with occasional complications and poor patient acceptance. This cohort study was designed to assess the accuracy of a noninvasive method aimed to discriminate between patients with and without significant liver fibrosis (stages 2-4 versus 0-1). Clinically relevant variables were analyzed in a cohort of 476 consecutive untreated patients (estimation group, 351 patients; validation group, 125 patients) with chronic hepatitis C who underwent a liver biopsy. Multivariate analysis identified age, gamma glutamyl transpeptidase (GGT), cholesterol, platelet count, and prothrombin time as independent predictors of fibrosis. We constructed a model and a score system combining age, GGT, cholesterol, and platelet count that proved useful to identify patients without significant hepatic fibrosis. The area under the ROC curve was 0.86 for the estimation group and 0.81 for the validation group. Using the best cutoff score (less than 4.2), presence of significant fibrosis (F2 to F4) could be excluded with high accuracy (negative predictive value of 96%) in 125 (36%) of 351 patients. Similarly, it could be excluded with the same certainty in 49 (39%) of the 125 patients of the validation group. Only 2 patients with liver fibrosis stage 2 were incorrectly classified. In conclusion, a combination of easily accessible variables accurately predicts the absence of significant fibrosis and might render liver biopsy unnecessary in more than one third of patients with chronic hepatitis C.

Adult↗

PubMed2002

Hypoxia is an inducer of vasodilator agents in peritoneal macrophages of cirrhotic patients.

The aim of the investigation was to assess whether hypoxia induces the production of endogenous vasoactive peptides in macrophages of cirrhotic patients with ascites because low tissue oxygenation is a relatively frequent event in these patients. Peritoneal macrophages were isolated from ascites, seeded on well plates, and cultured at different times under hypoxic (5% O(2)) or normoxic conditions (21% O(2)). Then, accumulation of vasoactive peptides sensitive to hypoxia including endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and adrenomedullin (ADM) was measured. Only VEGF and ADM were constitutively secreted, and hypoxia further stimulated the release of these vasodilator peptides. In concordance, increased messenger RNA (mRNA) levels of VEGF and ADM were found at culturing macrophages in hypoxia. This characteristic response was not observed in circulating monocytes of either cirrhotic patients or healthy subjects. Next the expression of the transcription factor, hypoxia inducible factor 1 (HIF-1), was analyzed. Expression of HIF-1alpha and HIF-1beta messengers and HIF-1beta protein subunit remained unchanged regardless of O(2) tension, whereas HIF-1alpha protein subunit was overexpressed under hypoxic conditions. Moreover, conditioned medium from macrophages cultured under hypoxic conditions promoted a larger nitric oxide (NO) release in endothelial cells than that of normoxic macrophages. In conclusion, these data indicate that hypoxia induces the synthesis of VEGF and ADM in macrophages of cirrhotic patients, likely through HIF-1-enhanced transcriptional activity. These data suggest that a local reduction in O(2) tension could enhance the synthesis of macrophage-derived vasodilators, thus aggravating the circulatory disturbance of these patients.

Adrenomedullin↗

PubMed2002

Hepatitis C: who should you treat and how?

At present the treatment of hepatitis C virus infection (HCV) has improved because of combined treatment with interferon (IFN) and ribavirin. The association of these two drugs has obtained a positive response in 40-50% of naive patients treated. Patients with relapse after monotherapy with IFN also show positive response with combined treatment in up to about 50% of patients with HCV genotype 1b. In patients with other genotypes the response is higher (up to 70%). In nonresponders to IFN alone, the response to combined therapy was higher although there is scarce data reporting this. Similar results were achieved in cirrhotic patients. The use of pegylated IFN has shown even greater efficacy. Sustained response was greater than 50%. Lastly, triple therapy with IFN, ribavirin and amantadine has been studied in small clinical trials in nonresponders to IFN monotherapy, with controversial results since in some studies sustained response was up to 48% being less than 20% in other studies.

Amantadine↗