Biomedical subjects
Publications and source records attributed to J Rodés.
Two women of 57 and 59 years of age, presented anicteric hepatitis at 9 months and 3 years, respectively, of the initiation of treatment with lovastatin (20 mg/day) for hypercholesterolemia. In both cases other causes of liver damage were excluded and the analytical alterations normalized within a few weeks following discontinuation of the medication.
The clinical and evolutive characteristics and the response to treatment of a series of 49 patients with autoimmune hepatitis (AIH) diagnosed in the Liver Unit of a tertiary hospital from 1979 to 1996 and followed over 5.6 +/- 0.7 years were reviewed. Forty cases (80.4%) were AIH type 1 (ANA/AML positive), 7 (14%) type 2 (ALKM positive) and 2 (5%) of an undetermined type (absence of detectable antibodies). In 13 (26.6%) the disease presented as acute hepatitis and 16 (32%) presented extrahepatic manifestations. The AIH type 2 was observed in younger patients with the debut being more acute than in AIH type 1, but no significant differences were observed between the two groups with regard to the results of laboratory tests, frequency of a systemic manifestations and histologic lesions. Immunosuppressive treatment was effective in 90% of the cases, but 11 (30%) out of 37 relapsed on suppression of prednisone or reduction of the dosis. All showed response on reinitiation or an increase in the dosis of prednisone. Progression to cirrhosis was observed in 17% of the patients without cirrhosis at the time of diagnosis despite biochemical remission induced by treatment. No patient died during the follow up but 4 required liver transplantation.
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Resistant coronary lesions remain a challenge for modern angioplasty. Classical approaches include high-pressure inflations, prolonged inflations, or balloon oversizing. More recently, new technologies like rotablator, atherectomy, or laser have been proposed as adjunct to balloon angioplasty for the treatment of these specific lesions. However, all these technologies remain more difficult to handle, costly, and they do not offer long-term benefit over conventional methods. Therefore, a simple device such as the cutting balloon catheter which has been developed from a standard over the wire balloon catheter, may prove to be useful in resistant coronary lesions. We present our single center experience using the new cutting balloon catheter in six resistant lesions.
Moderate physical exercise does not affect glomerular filtration rate (GFR) and renal excretory function in normal subjects. This study is aimed at assessing the effects of moderate physical exercise on renal function in 21 nonazotemic cirrhotic patients with ascites. Arterial pressure, heart rate, and renal function were assessed in the patients after 2 hours in the supine position and during 30 minutes of moderate cycloergometric exercise in the sitting position. The activity of the renin-aldosterone and sympathetic nervous systems and the plasma levels of antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) were determined at the end of each period. Physical exercise induced a marked reduction in GFR (75 +/- 10 to 49 +/- 6 mL/min), free-water clearance (6.1 +/- 1 to 3.4 +/- 1 mL/min), and sodium excretion (7.8 +/- 2 to 4.3 +/- 1 microEq/min) in 10 patients (Group I). In the remaining 11 cases (Group II) there were no changes in these parameters. Renal perfusion significantly decreased in both groups although the reduction was greater in Group I (-34.7% +/- 4.6% vs. -7.5% +/- 3.1%, P < .001). Physical exercise was associated with a significant and comparable increase in arterial pressure, heart rate, and plasma levels of renin, aldosterone, and norepinephrine (NE) in the two groups of patients. The ANP concentration did not change. Patients from Groups I and II differed significantly (P < .05) only in plasma renin activity (PRA) and NE concentration, which were higher in Group I patients both in the supine rest (renin: 4.7 +/- 1.6 vs. 1.4 +/- 0.5 ng/mL x h; NE: 576 +/- 115 vs. 288 +/- 42 pg/ mL) and during exercise (renin: 7.1 +/- 1.8 vs. 2.6 +/- 1 ng/ mL x h; NE: 925 +/- 135 vs. 630 +/- 90 pg/mL). In conclusion, moderate physical exercise has no detrimental effects on renal function in cirrhotic patients with ascites with no or mild activation of the renin-aldosterone and sympathetic nervous systems. However, moderate physical exercise causes a marked impairment in the renal function of patients with ascites with marked stimulation of these vasoconstrictor systems.
Ethanol intake depletes the mitochondrial pool of reduced glutathione (GSH) by impairing the transport of GSH from cytosol into mitochondria. S-Adenosyl-L-methionine (SAM) supplementation of ethanol-fed rats restores the mitochondrial pool of GSH. The purpose of the current study was to determine the effect of ethanol feeding on the kinetic parameters of mitochondrial GSH transport, the fluidity of mitochondria, and the effect of SAM on these changes. Male Sprague-Dawley rats were fed ethanol-liquid diet for 4 weeks supplemented with either SAM or N-acetylcysteine (NAC). SAM-supplementation of ethanol-fed rats restored the mitochondrial GSH pool but NAC administration did not. Kinetic studies of GSH transport in isolated mitochondria revealed two saturable, adenosine triphosphate (ATP)-stimulated components that were affected significantly by chronic ethanol feeding: lowering Vmax (0.22 and 1.6 in ethanol case vs. 0.44 and 2.7 nmol/15 sec/mg protein in controls) for both low and high affinity components with the latter showing an increased Km (15.5 vs. 8.9, mmol/L in ethanol vs. control). Mitochondria from SAM-supplemented ethanol-fed rats showed kinetic features of GSH transport similar to control mitochondria. Determination of membrane fluidity revealed an increased order parameter in ethanol compared with control mitochondria, which was restricted to the polar head groups of the bilayer and was prevented by SAM but not NAC supplementation of ethanol-fed rats. The changes elicited in mitochondria by ethanol were confined to the inner membrane; mitoplasts from ethanol-fed rats showed features similar to those of intact mitochondria such as impaired transport of GSH and increased order parameter. A different mitochondrial transporter, adenosine diphosphate (ADP)/ATP translocator, was unaffected by ethanol feeding. Furthermore, fluidization of mitochondria or mitoplasts from ethanol-fed rats by treatment with a fatty acid derivative restored their ability to transport GSH to control levels. Thus, ethanol-induced impaired transport of GSH into mitochondria is selective, mediated by decreased fluidity of the mitochondrial inner membrane, and prevented by SAM treatment.
Caroli's disease is an uncommon congenital disorder of the intrahepatic biliary tree. It is characterized by multiple and segmental dilatations of the bile ducts. The clinical course of Caroli's disease is often complicated by recurrent episodes of bacterial cholangitis that seriously impair the patient's quality of life. Despite wide spectrum antimicrobial agents, medical treatment of cholangitis is frequently unsuccessful in patients with Caroli's disease due to the persistence of bacteria in dilatated bile ducts. Other therapies, including internal or external biliary drainages and various surgical or endoscopic procedures, have been used in the treatment of Caroli's disease, with poor results. There are no previous reports in the literature of liver transplantation for recurrent cholangitis in patients with Caroli's disease. We present two such cases, in which cholangitis is resolved.
The purpose of this study was to determine the prevalence of osteoporosis, to estimate the bone turnover and hormonal status, and to identify the factors associated with bone disease in patients with end-stage liver disease who were referred for orthotopic liver transplantation. A prospective study was performed on 58 cirrhotic patients (6 with primary biliary cirrhosis, 14 with alcoholic cirrhosis, and 38 with posthepatitic cirrhosis), who were referred for orthotopic liver transplantation. Patients, excluding those with primary biliary cirrhosis, were classified in Child-Pugh groups according to the severity of liver disease (class B [28 patients], class C [24 patients]). Biochemical parameters of bone mineral metabolism and standard liver function tests were measured in all patients. Additionally, serum osteocalcin, urinary hydroxyproline/creatinine ratio, serum intact parathyroid hormone, serum 25-hydroxyvitamin D, serum 1,25-dihydroxyvitamin D, follicle-stimulating hormone, and luteinizing hormone levels were determined in patients and controls within the same age range. Plasma testosterone, sex hormone-binding globulin levels, and free testosterone index were obtained for all men included in the study. Bone mass of the lumbar spine and femur were measured by dual X-ray absorptiometry (DPX-L), and were expressed as a standard deviation of mean values (Z-score) from a sex and age-matched control group. Spinal X-rays were obtained to assess vertebral fractures. Osteoporosis was considered as a factor in spinal bone mineral density with a Z-score below 2 or at least one vertebral fracture. Twenty-five patients (43%) had osteoporosis, with lower bone mass measurements in the lumbar spine than in the femoral neck (P < 0.005). Alcoholic and Child-Pugh C patients showed the lowest femoral bone mineral density values. Cirrhotic patients showed lower osteocalcin levels than controls (14.3 +/- 5.9 vs. 18.2 +/- 8.1 ng/ml; P < 0.05) and showed increased urinary hydroxyproline (125.1 +/- 51.5 vs. 107.9 +/- 26.6 nM/mg creatinine; P < 0.05). Serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone levels were significantly lower in cirrhotic patients than in controls (10.3 +/- 9.1 vs. 23.1 +/- 26.6 ng/ml; P = 0.000), (12.9 +/- 9.1 vs. 48.3 +/- 11.5 pg/ml; P = 0.000), (16.6 +/- 9.2 vs. 27.9 +/- 8.2 pg/ml; P = 0.000), with no differences between Child-Pugh groups. Alcoholic Child-Pugh C patients showed the lowest 25-hydroxyvitamin D serum values (4.5 +/- 2.2 ng/ml; P < 0.05). Male patients had lower testosterone levels than controls (302.5 +/- 229.4 vs. 556.7 +/- 146.5 ng/dl; P = 0.000), with increased sex hormone-binding globulin values. Levels of testosterone and gonadotropin were related to Child-Pugh classification. No correlation was found between bone mass and hormonal values. A significant decrease in bone mass, particularly in the lumbar spine, is seen in end-stage cirrhotic patients. Reduced bone formation and significant disorders of bone mineral metabolism, such as vitamin D deficiency, reduced parathyroid hormone levels, and hypogonadism are involved. Moreover, severity and etiology of the liver disease are the main risk factors for developing bone loss and mineral metabolism disorders in patients referred for orthotopic liver transplantation.
BACKGROUND & AIMS: Because osteopenia increases morbidity of primary biliary cirrhosis (PBC), the effects of cyclical etidronate vs. sodium fluoride on bone mass were compared in patients with PBC. METHODS: Thirty-two women with PBC were randomly assigned to receive etidronate (400 mg/day during 14 days every 3 months) or fluoride (50 mg/day, enteric-coated tablets). Bone mineral density of the lumbar spine and proximal femur were measured initially and every 6 months. Bone fractures were also evaluated. RESULTS: Sixteen patients were allocated into each group, which were comparable with respect to the severity of PBC and osteopenia. Thirteen patients with etidronate and 10 patients with fluoride completed 2 years in the study. In the etidronate group, bone mineral density increased in the lumbar spine (P = 0.02) and did not change in the proximal femur. In the fluoride group, lumbar bone mineral density did not change but femoral bone mass decreased, particularly in the Ward's triangle. Two patients in the fluoride and none in the etidronate group developed new vertebral fractures, and the number of new nonvertebral fractures was similar in both groups. Neither treatment impaired liver function or cholestasis. CONCLUSIONS: Cyclical etidronate is more effective and better tolerated than sodium fluoride in preventing bone loss in PBC.
BACKGROUND & AIMS: Increased portal blood flow represents a compensatory mechanism preventing hepatic hypoxia after ethanol consumption. In addition, alcohol increases hepatic vascular resistance. Thus, ethanol consumption, by increasing hepatic vascular resistance and portal flow, may worsen portal hypertension in patients with cirrhosis. The aim of this study was to investigate the effects of ethanol consumption on hepatic hemodynamics in patients with alcohol-induced cirrhosis. METHODS: Measurements of hepatic venous pressure gradient (HVPG), azygos blood flow, hepatic blood flow, heart rate, and arterial pressure were obtained in 16 patients with alcohol-induced cirrhosis and portal hypertension before and after random administration of a noncaloric fruit drink (250 mL, n = 7) or of an identical beverage plus 0.5 g/kg of ethanol (n = 9). RESULTS: Vehicle caused no effects. By contrast, ethanol increased HVPG (P < 0.0001). The increase in HVPG was maximum at 15 minutes and remained significant at 45 minutes (P < 0.05 vs. vehicle). Ethanol increased azygos blood flow (P < 0.05) without changes in hepatic blood flow. Heart rate and arterial pressure slightly increased. CONCLUSIONS: Oral ethanol consumption increases portal pressure and portocollateral blood flow in patients with alcohol-induced cirrhosis. These findings suggest that even moderate alcohol consumption worsens the portal-hypertensive syndrome and, therefore, may increase the risk of variceal bleeding in patients with alcohol-induced cirrhosis.
BACKGROUND/AIMS: The plasma levels of endothelin (ET) are 2-5 fold higher in patients with cirrhosis than in healthy subjects. It has been proposed that endotoxemia could be a mechanism responsible for this phenomenon. However, investigations in rats with cirrhosis indicate that a differential regulation for prepro ET-1 mRNA expression occurs in the liver tissue of these animals but not in the aorta or other organs. The aim of the study was to investigate the effect of bacterial lipopolysaccharide (LPS) on endothelin-1 synthesis and release in cultured human vascular endothelial cells (HUVEC). METHODS: Confluent HUVEC at passage levels 3 and 4 were exposed to increasing doses of LPS (1-1000 ng/ml) for 4 h at 37 degrees C and prepro ET-1 mRNA accumulation and big ET-1 and ET-1 concentrations in the conditioned medium were measured. RESULTS: Endotoxin had a dual effect on HUVEC. LPS at doses ranging between 250 and 1000 ng/ml induced a progressive diminution in ET-1 concentration in the culture medium. However, lower LPS concentrations dose-dependently increased big ET-1 and ET-1 release by HUVEC without altering prepro ET-1 mRNA expression. CONCLUSIONS: These results suggest that low LPS concentrations promote ET-1 release in HUVEC by a post-transcriptional mechanism located upstream of big ET-1 in the biosynthetic pathway of ET-1. These findings could explain the existence of high circulating levels of ET-1 in cirrhosis in spite of transcriptional activation of prepro ET-1 mRNA only occurring in the liver.
BACKGROUND/AIMS: Selective intestinal decontamination with norfloxacin is widely used to prevent spontaneous bacterial infections in cirrhosis. The study was performed to compare the spontaneous bacterial peritonitis occurring in patients with and without prophylactic norfloxacin. METHODS: Two hundred and twenty-nine consecutive episodes of spontaneous bacterial peritonitis, (193 in patients without (Group A) and 36 in patients with norfloxacin prophylaxis (Group B)), were retrospectively analyzed. In 100 episodes (86 and 14, respectively), the responsible organism was isolated in ascitic fluid. RESULTS: Clinical and laboratory data at diagnosis were comparable in both groups. There were marked differences (p < 0.001) between group A and B in the frequency of peritonitis caused by gram-negative (67.4% vs. 14.3%) and gram-positive (30.2% vs. 78.6%) bacteria. There were three polymicrobial episodes. Bacteria resistant to cefotaxime and gram-negative bacilli resistant to quinolones were isolated in ascitic fluid in nine (seven in Group A and two in Group B) and three episodes (all in Group A), respectively. No differences in the course of infection and patient survival were observed between groups. CONCLUSIONS: Spontaneous bacterial peritonitis in patients with and without prophylaxis with norfloxacin are not different in clinical features, response to treatment and prognosis. Spontaneous bacterial peritonitis caused by gram-negative organisms resistant to quinolones is extremely uncommon in patients with cirrhosis receiving prophylactic norfloxacin.
BACKGROUND/AIMS: Circulatory abnormalities with activation of vasoconstrictor systems after large-volume paracentesis are generally considered secondary to an increased extravasation of fluid from the intravascular compartment to the extravascular space with subsequent reduction in plasma volume. To test this hypothesis, plasma volume, the transvascular escape rate of albumin, the absolute escape rate of albumin and the activity of vasoconstrictor systems were measured in 25 cirrhotic patients with ascites in baseline conditions and 2 days after total paracentesis with plasma volume expansion. METHODS: Plasma volume and the transvascular escape rate of albumin, the fraction of albumin passing from the intravascular to the extravascular space per unit of time, were assessed through the plasma disappearance curve of radioiodinated human albumin. The absolute escape rate of albumin, the total flux of albumin from intravascular to extravascular space per unit of time, was also calculated. RESULTS: Eight of the 25 patients (32%) developed marked activation of vasoconstrictor systems after paracentesis. In these patients, plasma renin activity and plasma norepinephrine concentration increased from 6.6+/-2 to 23.4+/-11 ng x ml(-1) x h(-1) and 776+/-229 to 989+/-258 pg/ml, respectively (p<0.05). No significant changes in these parameters were found in the remaining 17 patients. The activation of vasoconstrictor systems occurred in the absence of changes in plasma volume (3456+/-276 vs 3476+/-264 ml, NS), transvascular escape rate of albumin (10.4+/-1 vs 10.9+/-2%/h, NS) and absolute escape rate of albumin (9.9+/-1.9 vs 10.5+/-0.7 g/h, NS). CONCLUSIONS: These results do not support a contraction of plasma volume as the mechanism responsible for activation of vasoconstrictor systems after paracentesis. Rather, the activation of vasoconstrictor systems in the absence of changes in plasma volume suggests that paracentesis accentuates the impairment of "effective" blood volume present in cirrhotic patients with ascites.
BACKGROUND/AIMS: The influence of the infecting virus genotype on the progression of the underlying liver disease in patients with chronic hepatitis C virus (HCV) infection remains controversial. The aim of this study was to investigate the prevalence of HCV genotypes in Spanish patients with chronic HCV infection and to elucidate the relationship between the infecting genotype and the severity of the disease. METHODS: A cross-sectional, retrospective analysis of frequency distribution of HCV genotypes was carried out in 414 Spanish patients with chronic HCV infection, including 243 patients with asymptomatic or minimally symptomatic chronic hepatitis, 112 patients with cirrhosis and hepatocellular carcinoma and 59 patients with decompensated cirrhosis. HCV genotype was determined by restriction fragment length polymorphisms of the 5' non-coding region. RESULTS: Infection with HCV genotype 1b was found in 72% of patients with chronic hepatitis and in more than 90% of patients with cirrhosis, with or without hepatocellular carcinoma. Older age, infection with genotype 1b and absence of overt parenteral exposure as a possible source of infection were associated with cirrhosis and hepatocellular carcinoma by univariate analysis and this association was confirmed by regression analysis. CONCLUSIONS: HCV genotype 1b is associated with advanced liver disease in our geographical area. However, this may be related to a cohort-effect caused by over-representation of genotype 1b in older patients with more advanced disease, because, in our country, this HCV genotype appeared earlier in time and is therefore associated with more prolonged periods of infection.
BACKGROUND/AIMS: The pathogenic relevance of the hepatitis G virus (HGV) and its sensitivity to interferon are currently under investigation. This study aimed to investigate the prevalence of HGV infection in patients with chronic hepatitis C and to elucidate if HGV co-infection modifies the clinical course and the response to interferon therapy in this disease. METHODS: HGV-RNA was investigated by reverse transcription-polymerase chain reaction in serum from 143 consecutive patients who received interferon alpha-2b (3 MU t.i.w.) for 24 weeks. Baseline features and response to therapy in HGV-infected and non-infected patients were compared. To assess the antiviral effect of interferon, serial quantitative measurement of HCV-RNA and HGV-RNA in serum was performed in patients co-infected with HCV and HGV. RESULTS: Eight patients (5.6%) presented HGV-RNA sequences in serum. No significant differences were found between HGV-infected and non-infected patients in relation to age, sex, source of infection, liver function tests, liver histology and HCV genotype, nor in the biochemical response to interferon, which was sustained in 12% and 15%, transient in 37% and 30% and absent in 50% and 55% of HGV-infected and non-infected patients, respectively. HGV-RNA became negative in all treated patients, but sustained viral inhibition was observed only in those with low viral load. CONCLUSIONS: The prevalence of HGV infection in HCV-infected patients is relatively low in our geographical area. HGV co-infection does not appear to modify the clinical presentation nor the response to interferon in chronic hepatitis C. HGV is sensitive to interferon, particularly if pre-treatment viral load is low.
BACKGROUND/AIMS: To investigate a possible relationship between the renal production of endothelin and the presence of renal dysfunction and activation of vasoactive systems in cirrhosis, the urinary excretion and the circulating plasma levels of immunoreactive endothelin (irET) and the plasma levels of vasoactive hormones were measured in 19 healthy subjects, 12 cirrhotic patients without ascites and 39 patients with ascites and different degrees of renal dysfunction. METHODS: The urinary excretion and the circulating levels of irET were assessed after 5 days on a 40 mEq sodium diet and off diuretics. Renal function parameters and the plasma levels of vasoactive hormones were also measured. RESULTS: Patients with and without ascites had similar values of urinary irET as compared with healthy subjects (30+/-3, 31+/-3 and 29+/-2 ng/day, respectively, p>0.10). By contrast, patients with ascites had higher circulating levels of irET (15+/-1.2 pg/ml) than patients without ascites and healthy subjects (11+/-1.6 and 5+/-0.4 pg/ml, p<0.01). In patients with cirrhosis, no correlation was found between urinary irET and circulating irET. Moreover, urinary irET did not correlate with liver tests, serum and urine sodium, glomerular filtration rate or vasoactive substances. Patients with hepatorenal syndrome had similar urinary irET to patients with ascites without hepatorenal syndrome. CONCLUSIONS: Urinary excretion of irET is not increased in cirrhotic patients with ascites and does not correlate with abnormalities in renal function.
BACKGROUND/AIMS: Due to structural and functional similarities between platelets and vascular smooth muscle cells, platelet cytosolic calcium concentration ([Ca2+]i) has been suggested to be a useful tool to study regulatory mechanisms of peripheral vascular tone. The aim of the present study was to investigate platelet [Ca2+]i in patients with cirrhosis and whether this parameter is related with the systemic and splanchnic vasodilatation found in these patients. METHODS: Seventeen patients with cirrhosis and eight age- and sex-matched controls were studied. Mean arterial pressure, cardiac output, femoral blood flow and basal and thrombin-stimulated platelet [Ca2+]i were measured. Cardiac output (thermal dilution), azygos blood flow, hepatic venous pressure gradient and hepatic blood flow were also measured in patients with cirrhosis. RESULTS: Patients with cirrhosis had severe portal hypertension and a significantly higher cardiac output and femoral blood flow and a significantly lower systemic and femoral vascular resistance than controls. Patients with cirrhosis had a lower basal platelet [Ca2+]i than normal subjects. However, there was no relationship between platelet [Ca2+]i and any of the hemodynamic parameters that evaluate systemic or splanchnic vasodilatation. CONCLUSIONS: This study shows that cirrhotic patients with portal hypertension have a significant reduction in platelet basal [Ca2+]i. The lack of correlation between platelet [Ca2+]i and hepatic and systemic hemodynamics does not support the use of platelet [Ca2+]i as a model to study mechanisms involved in the pathophysiology of the hyperdynamic circulation associated to portal hypertension.
BACKGROUND/AIMS: Terlipressin is a long-acting vasopressin analogue that has been proved useful in the treatment of variceal haemorrhage. This study investigates the time profile of the haemodynamic effects of terlipressin on portal hypertension as well as the efficacy in decreasing portal-pressure and collateral blood flow of reduced doses, suitable for longer therapy to prevent early rebleeding. METHODS: Splanchnic and systemic haemodynamics were measured in 23 patients with cirrhosis and portal hypertension in baseline conditions and at 30 min, 1, 2, 3 and/or 4 h after the double-blind administration of a single intravenous injection of 1 mg (n=8) or 2 mg (n=8) of terlipressin, or placebo (n=7). RESULTS: Placebo caused no significant effects. At 30 min of terlipressin administration, the hepatic venous pressure gradient (1 mg: -16+/-9%, 2 mg: -21+/-11%; p<0.01) and azygos blood flow (1 mg: -19+/-13%, 2 mg: -25+/-17%; p<0.05) were significantly reduced. These effects were still significant at 4 h (2 mg) or 3 h (1 mg). Both doses moderately increased arterial pressure at 1 h. At 4 h, neither arterial pressure nor peripheral vascular resistance was significantly modified by either dose of terlipressin. Terlipressin caused no significant changes in hepatic blood flow. CONCLUSIONS: In patients with cirrhosis, a single injection of 2 mg of terlipressin significantly and markedly reduces portal pressure and azygos blood flow for up to 4 h. The effects of a reduced dose (1 mg) were almost as pronounced and prolonged, suggesting that after the initial control of variceal bleeding, terlipressin therapy could be maintained for several days at low dosage to reduce the risk of early rebleeding.