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Biomedical subjects

J Rodés

Publications and source records attributed to J Rodés.

At least 253 records · Page 14Linked to original sources

Gastric microcirculatory changes of portal-hypertensive rats can be attenuated by long-term estrogen-progestagen treatment.

It has been suggested that estrogen-progestagen therapy may be useful in preventing bleeding from gastric angiodysplasia, a vascular lesion similar to that described in portal-hypertensive gastropathy. In this study we assessed the effects of estrogen-progestagen therapy on gastric microcirculation and systemic and splanchnic hemodynamics in portal-hypertensive and sham-operated rats. One week after the surgical procedure (partial portal vein ligation or sham surgery), animals were given an intramuscular injection of a slow-release preparation of estrogen-progestagen or its vehicle. Two weeks later, gastric mucosal blood flow was measured by means of hydrogen gas clearance, a morphometrical analysis of gastric mucosal blood vessels was performed and systemic and splanchnic hemodynamics were evaluated with a radiolabeled-microspheres technique. In portal-hypertensive rats, estrogen-progestagen therapy induced a significant reduction in gastric mucosal blood flow, number of blood vessels and relative area of vessels. Similar changes, although of lesser magnitude, were achieved with estrogen or progestagen given separately and with the low dose of combined estrogen-progestagen. Estrogen-progestagen treatment also induced significant reductions in portal pressure and porto-collateral resistance without changing systemic or splanchnic hemodynamics. In contrast, estrogen-progestagen treatment did not induce changes in any of the parameters studied in sham-operated rats. We conclude that long-term estrogen-progestagen therapy reduces the gastric hyperemia, increased mucosal vessel density and portal pressure in portal-hypertensive rats.

Animals↗

Renal impairment after spontaneous bacterial peritonitis in cirrhosis: incidence, clinical course, predictive factors and prognosis.

Although spontaneous bacterial peritonitis is considered a precipitating factor of renal impairment in cirrhosis, no study specifically addressing this problem has been reported. This study was aimed at assessing the incidence, clinical course, predictive factors and prognosis of renal impairment in cirrhotic patients with peritonitis. Therefore, 252 consecutive episodes of spontaneous bacterial peritonitis in 197 patients were analyzed. Clinical and laboratory data obtained before and after diagnosis of peritonitis were considered as possible predictors of renal impairment and hospital mortality. Renal impairment occurred in 83 (33%) episodes, and in every instance it fulfilled the criteria of functional kidney failure. Renal impairment was progressive in 35 episodes, steady in 27 and transient in 21. Blood urea nitrogen and serum sodium concentration before peritonitis and band neutrophils count in blood at diagnosis were independent predictors for the development of renal impairment. Renal impairment was the strongest independent predictor of mortality during hospitalization. Other independent prognostic factors were blood urea nitrogen level before peritonitis, age, positive ascitic fluid culture and serum bilirubin level during infection. These results indicate that renal impairment is a frequent event in cirrhotic patients with spontaneous bacterial peritonitis that occurs mainly in patients with kidney failure before infection. Renal impairment is the most important predictor of hospital mortality in cirrhotic patients with spontaneous bacterial peritonitis.

Adult↗

Increased nitric oxide-dependent vasorelaxation in aortic rings of cirrhotic rats with ascites.

To assess whether aortic vessels of rats with cirrhosis and ascites possess an enhanced vascular response to endothelium-derived, nitric oxide-dependent vasodilators, we performed relaxation studies in isolated aortic rings of 21 control rats and 24 rats with carbon tetrachloride-induced cirrhosis and ascites. We carried out studies after contracting the vessels with norepinephrine. We measured endothelium-dependent vasodilator response by administering increasing concentrations of acetylcholine (10(-6) to 10(-2) mol/L) and ADP (10(-7) to 10(-4) mol/L). We evaluated endothelium-independent response by giving increased concentration of sodium nitrite (10(-5) to 10(-2) mol/L). The maximal absolute tension developed in response to norepinephrine was significantly decreased in cirrhotic rings (816 +/- 72 mg, p < 0.025) compared with control (1,425 +/- 75 mg) rings. Dose-response curves for endothelium-dependent vasodilators were shifted to the left in aortic rings of cirrhotic rats, and EC50 for acetylcholine and ADP were significantly decreased in cirrhotic (0.8 +/- 0.15 mmol/L and 0.42 +/- 0.16 mumol/L, p < 0.025 and p < 0.01, respectively) than in control rings (1.91 +/- 0.33 mmol/L and 3.09 +/- 0.82 mumol/L). In both acetylcholine- and ADP-stimulated vessels, differences between cirrhotic and control rings disappeared after nitric oxide synthesis inhibition with N omega-nitro-L-arginine (10(-4) mol/L). No difference in the relaxing effect of sodium nitrite was observed between cirrhotic and control rings. These results therefore demonstrate for the first time enhanced in vitro vascular responsiveness to nitric oxide-dependent vasodilators in rats with cirrhosis and ascites, giving further support to the concept that nitric oxide activity is increased in cirrhosis.

Acetylcholine↗

Bone mass improves in alcoholics after 2 years of abstinence.

To evaluate the effect of abstinence on bone mass and bone mineral metabolism in chronic alcoholics, a 2 year longitudinal follow-up study was carried out in a group of 30 chronic alcoholic males who started a rehabilitation program. Lumbar and femoral bone mineral density (BMD) and serum levels of osteocalcin and 25-hydroxyvitamin D were measured at entry and after 1 and 2 years in all patients. Circulating cortisol and parathyroid hormone were measured in 14 and 6 patients, respectively, at entry and every year. Testosterone was measured in 18 patients at entry and after 1 year. At entry, lumbar BMD was significantly lower in alcoholics (1.06 +/- 0.03 g/cm2) than in age-matched healthy men (1.22 +/- 0.03 g/cm2; p < 0.001). Circulating osteocalcin and vitamin D levels were also significantly lower in alcoholics than in controls. Lumbar and femoral neck BMD increased in alcoholics after 2 years of abstinence (lumbar BMD, mean +/- SEM, 1.06 +/- 0.03 to 1.10 +/- 0.04 g/cm2, p < 0.05; femoral BMD, 0.82 +/- 0.02 to 0.84 +/- 0.02 g/cm2; p < 0.02). Moreover, lumbar BMD increased in alcoholics (2.9 +/- 1.4%) and decreased in controls (-1.1 +/- 0.2%; p < 0.02). Femoral BMD also increased in alcoholics (2.8 +/- 1.0%) but the expected mean decrease of -0.92% was found in healthy age-matched males. Baseline low osteocalcin levels (5.1 +/- 0.6 ng/ml) increased after 1 year (8.6 +/- 0.5 ng/ml, p < 0.001) and 2 years of abstinence (9.5 +/- 0.7 ng/ml, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

25-Hydroxyvitamin D 2↗

Erythromycin ototoxicity in liver transplant patients.

We report on three liver transplant patients who developed erythromycin-related ototoxicity. This complication has been described in renal transplant patients and in patients with liver dysfunction, but to our knowledge it has not yet been reported in liver transplant patients. The influence of hepatic dysfunction, common renal failure, and the interaction between cyclosporin and erythromycin in the development of erythromycin ototoxicity are discussed.

Adult↗

Diabetes mellitus in patients with liver cirrhosis.

In spite of the high prevalence of diabetes mellitus (DM) in patients with liver cirrhosis (LC) few studies have focused on the clinical implications of this association. We investigated the clinical and pancreatic-endocrine features of 34 patients who developed DM after LC (Group I). Results were compared with 34 carefully matched patients with only Type II DM (Group II). A standard meal test was performed in 26 patients with normal renal function from each group to assess beta-cell function. Group I patients, less frequently had retinopathy (14.7% vs. 45.5%, P < 0.05) and a family history of diabetes (23.5% vs. 58.8%, P < 0.01). Group I patients also showed signs of enhanced insulin resistance, reflected by higher insulin dose requirements in insulin-treated patients (0.87 +/- 0.10 vs. 0.62 +/- 0.05 IU/kg/day, P < 0.01) and increased basal C-peptide values (0.88 +/- 0.06 vs. 0.68 +/- 0.07 pmol/l, P < 0.05, respectively) than those in Group II. These results suggest that several clinical features, probably related to the hepatopathy, define DM occurring in patients with LC.

Blood Glucose↗

Favorable effects of total paracentesis on splanchnic hemodynamics in cirrhotic patients with tense ascites.

Total paracentesis is widely used in the treatment of patients with cirrhosis and tense ascites. However, very little information is available regarding its consequences on splanchnic circulation, and its effects on portocollateral blood flow have not been investigated. Ten cirrhotic patients admitted because of tense ascites had measurements of hepatic and systemic hemodynamics, renal function and endogenous vasoactive neurohumoral systems at baseline, just after total paracentesis and 1 hr later. Total paracentesis caused a significant increase in cardiac output (+11%; 95% confidence interval, +4% to +19%) and a rapid fall in portal pressure, as shown by significant decreases in both the wedged hepatic venous pressure (-27% +/- 8%; p < 0.005) and the hepatic venous pressure gradient (-10%; 95% confidence interval, -3% to -18%). This was accompanied by a marked decrease in azygos blood flow (-28%; 95% confidence interval, -13% to -43%). These favorable hemodynamic effects were associated with a fall of the elevated levels of plasma renin activity (-47% +/- 9%; p < 0.05), plasma aldosterone (-31% +/- 21%; p < 0.05) and plasma norepinephrine and by a decrease in levels of serum creatinine (-24% +/- 15%; p < 0.05) and blood urea nitrogen (-4% +/- 3%; p < 0.05). These changes were maintained 1 hr later. This study indicates that in patients with cirrhosis and tense ascites total paracentesis favorably influences the systemic hemodynamics, portocollateral blood flow and portal pressure.

Aged↗

Nicardipine increases hepatic blood flow and the hepatic clearance of indocyanine green in patients with cirrhosis.

The present study investigated the hemodynamic effects of nicardipine, a new calcium channel blocker, and placebo in 14 patients with cirrhosis. Sixty minutes after nicardipine administration (20 mg orally; n = 8), there was a significant increase in hepatic blood flow (25 +/- 21%; p < 0.05) and azygos blood flow (33 +/- 40%; p < 0.05) but no significant change in the hepatic venous pressure gradient. As a result of the increase in hepatic blood flow and the lack of change in the hepatic venous pressure gradient, nicardipine significantly reduced hepatic sinusoidal resistance (-14 +/- 15%; p < 0.05). Enhanced liver perfusion was associated with a significant increase in the hepatic clearance of indocyanine green (from 241 +/- 81 to 265 +/- 92 ml/min, p < 0.05). A mild, well-tolerated decrease in mean arterial pressure (-10 +/- 6%, p < 0.05), without significant changes in cardiac output, systemic vascular resistance and heart rate, was also observed. Placebo administration (n = 6) did not cause significant changes in systemic or hepatic hemodynamics. The results of the present study show that nicardipine, unlike other calcium channel blockers, effectively increases hepatic blood flow and the hepatic clearance of indocyanine green in patients with cirrhosis. The acute beneficial effects of nicardipine should be confirmed in chronic studies.

Aged↗

Fibrogenic and collagenolytic activity in carbon-tetrachloride-injured rats: beneficial effects of zinc administration.

Collagen synthesis and degradation in normal and carbon-tetrachloride-injured male Wistar rats at early and late stages of liver fibrosis, and the potential beneficial effects of zinc supplementation on liver fibrogenesis and collagenolysis have been assessed by measuring hepatic collagen content and prolyl hydroxylase and collagenase activities. No significant changes in hepatic collagen and prolyl hydroxylase activities were observed between control rats (82 +/- 25 cpm/mg protein) and rats with induced cirrhosis (107 +/- 23 cpm/mg protein) after 4 weeks of carbon tetrachloride injury. By this time, hepatic collagenase activity was significantly lower in rats with induced cirrhosis (61 +/- 9 micro units/mg protein) than in control rats (133 +/- 31 micro units/mg protein) (p < 0.05). This result was prevented by zinc administration, since hepatic collagenase activity was similar in zinc-supplemented, carbon-tetrachloride-injured rats and normal rats (148 +/- 19 micromicrons/mg protein). After 16 weeks, all carbon-tetrachloride-injured rats had cirrhosis. Hepatic collagen content and prolyl hydroxylase activity were significantly higher in carbon-tetrachloride-injured rats than in controls. These effects were partially prevented by zinc administration, since only two of the seven zinc-supplemented, carbon-tetrachloride-injured rats had cirrhosis. Moreover, prolyl hydroxylase activity was significantly lower in zinc-supplemented injured rats (263 +/- 27 cpm/mg protein) than in the non-supplemented respective controls (389 +/- 52 cpm/mg protein) (p < 0.05). No significant changes in hepatic collagenase activity were observed at this stage of liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Blunted natriuretic response to human urine extracts with Na+,K(+)-ATPase inhibiting activity in experimental cirrhosis.

Human urine and plasma extracts contain a material that inhibits the enzyme Na+,K(+)-ATPase (the endogenous sodium pump) and produces natriuresis in the bioassay animal. This endogenous sodium pump inhibitor(s), also known as digitalis-like factor, is thought to be involved in sodium and extracellular fluid volume homeostasis. Increased urine and plasma sodium pump inhibiting activity have been reported in patients with cirrhosis and sodium retention. The aim of the study was to assess the renal response to i.v. administration (0.2 ml/min per kg bw for 10 min) of a human urine extract containing sodium pump inhibiting activity (28.5 nmol equivalent ouabain/ml) in eight conscious rats with cirrhosis and ascites and eight control rats. Baseline urinary excretion of Na+,K(+)-ATPase inhibiting activity was significantly higher in cirrhotic rats with ascites than in control rats (235 +/- 40 vs 91 +/- 16; p < 0.01). Human urine extract induced a significant (p < 0.05) increase in glomerular filtration rate in control (3.2 +/- 0.4 to 4.2 +/- 0.5 ml/min) and cirrhotic rats (3.0 +/- 0.3 to 4.0 +/- 0.5 ml/min). In control rats it also increased urinary sodium excretion (1.47 +/- 0.22 to 2.43 +/- 0.5 microEq/min, p < 0.01) and fractional sodium excretion (0.29 +/- 0.01 to 0.43 +/- 0.04%, p < 0.025). In contrast, in cirrhotic rats with ascites neither sodium excretion nor fractional sodium excretion was significantly affected. No changes were observed in plasma aldosterone and atrial natriuretic peptide concentrations in either group. These data suggest that in cirrhosis there is a renal resistance to the natriuretic effect of endogenous sodium pump inhibitor(s).

Animals↗

Intracellular calcium concentration in vascular smooth muscle cells of rats with cirrhosis.

A decreased pressor response to endogenous vasoconstrictors, such as angiotensin II and vasopressin, is a characteristic finding in cirrhosis with ascites; this has been considered as partially responsible for the arteriolar vasodilation present in this disease. Previous investigations suggested that this abnormality is due to a post-receptor defect leading to altered intracellular Ca2+ mobilization. To assess this hypothesis, vascular responsiveness to angiotensin II (3.10(-8) M) and intracellular Ca2+ concentration in basal conditions and following angiotensin II (1-100 nM) and vasopressin stimulation (100 nM) were measured in aortic rings and in primary cultured aortic vascular smooth muscle cells, respectively. The study was carried out in 43 control rats and 40 rats with CCl4-induced cirrhosis and ascites. Cells were grown to confluence on glass cover slips and then loaded with Fura-2, a fluorescent intracellular Ca2+ indicator, for continuous monitoring of intracellular Ca2+ concentration. A decreased constrictor response to angiotensin II was detected in cirrhotic aortic rings in comparison to control rings (increase in tension: 31 +/- 5 vs 79 +/- 14 mg, p < 0.005). No differences in intracellular Ca2+ concentration between cirrhotic and control cells were observed in basal conditions (104 +/- 6 and 100 +/- 3 nM, respectively). Angiotensin II administration to cirrhotic vascular smooth muscle cells had a dose-dependent biphasic effect consisting of a rapid increase, followed by return to a sustained level significantly higher than the basal value. This response was identical to that observed in control vascular smooth muscle cells. Similar findings were obtained following vasopressin stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Cross-reactivity of anti-Mycobacterium gordonae antibodies with the major mitochondrial autoantigens in primary biliary cirrhosis.

Primary biliary cirrhosis is a chronic cholestatic liver disease associated with autoimmune disorders. Antimitochondrial autoantibodies and granulomatous portal lesions are characteristic in primary biliary cirrhosis. Since granuloma may be induced by Mycobacteria, and there is evidence implicating Mycobacteria as infectious agents capable of initiating autoimmunity, a study was performed to determine the presence of antibodies against 10 atypical Mycobacteria in 19 patients with primary biliary cirrhosis, and in 35 controls (25 patients with other chronic liver diseases and 10 healthy subjects). All primary biliary cirrhosis sera and none of the controls reacted with the extract from Mycobacterium gordonae, showing identical recognition profiles with two polypeptides of 70-65 and 55 kDa. No other reaction was found in primary biliary cirrhosis patients and in controls with the extracts from the other nine atypical Mycobacteria tested. Eluted immunoglobulins which reacted with the 70-65 and 55 kDa polypeptides from M. gordonae, bound to the mitochondrial antigens PDH-E2 and BCKDH-E2. Furthermore, when the extract from M. gordonae was tested with eluted immunoglobulins from recognized PDH-E2 and BCKDH-E2 by primary biliary cirrhosis patients, we observed both 70-65 and 55 kDa polypeptides. These data indicate that antibodies to M. gordonae, found in all primary biliary cirrhosis patients, cross-react with the major mitochondrial targets of the disease. We suggest that M. gordonae may play a potential pathogenic role in primary biliary cirrhosis.

Antibodies, Bacterial↗

Cyclosporin A increases the biochemical markers of bone remodeling in primary biliary cirrhosis.

To assess whether cyclosporin A has any influence on the bones of patients with primary biliary cirrhosis, bone mineral density, vertebral fractures and biochemical and hormonal parameters of bone mineral metabolism were evaluated in 38 female patients with primary biliary cirrhosis who, 7 to 47 months previously, had been randomized to receive cyclosporin A (n = 18) or placebo (n = 20). Bone mineral density and vertebral fractures were reevaluated after 12 to 47 months in 19 of these patients (ten with cyclosporin and nine with placebo). Serum osteocalcin levels in patients taking cyclosporin (median, range: 7.8, 4.2-16 ng/ml) were similar to healthy female controls (6.0, 4.7-9.5 ng/ml), and significantly higher than in patients receiving placebo (5.4, 1.0-8.6 ng/ml, p < 0.02). Patients treated with cyclosporin showed a higher urinary hydroxyproline/creatinine ratio (0.097, 0.025-0.138) than patients with placebo (0.031, 0.022-0.044) (0.05 > p < 0.1), and healthy controls (0.032, 0.021-0.048) (p < 0.001). Urinary hydroxyproline was above normal levels in six of nine patients treated with cyclosporin. Circulating parathyroid hormone levels were also higher in patients treated with cyclosporin (4.3, 2.0-9.0 pmol/l) than in those with placebo (3.1, 1.1-5.1 pmol/l) (p < 0.001), and healthy controls (2.9, 1.1-6.9 pmol/l) (p < 0.001). In four patients treated with cyclosporin the parathyroid hormone levels were above normal values. No patient had renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Epidemiology of primary sclerosing cholangitis in Spain. Spanish Association for the Study of the Liver.

The incidence of primary sclerosing cholangitis has been estimated on the basis of its frequent association with ulcerative colitis, but direct epidemiologic studies have not yet been carried out. In the current study we report a survey of clinical and epidemiological aspects of primary sclerosing cholangitis in Spain. A questionnaire was circulated to physicians in 33 hospitals throughout Spain to ascertain the number and the clinical, biochemical and immunologic characteristics of patients with primary sclerosing cholangitis from January 1, 1984 to December 31, 1988. Twenty-three centers, from 12 Spanish regions, covering a population of 19.23 million answered the questionnaire. Forty-three patients (60.5% males) with a mean age of 42.3 years (range 12 to 75 years) were seen during the 5-year period. At presentation, 16% of the cases were asymptomatic. Ulcerative colitis was present in 44.2% of cases, and one patient had Crohn's disease. The overall annual incidence ranged from 0.16 to 0.68 cases/million from 1985 to 1988, and the annual prevalence increased from 0.78 cases/million in 1984 to 2.24 cases/million in 1988. No geographical differences were found, but there was a trend to detect more cases in industrialized regions. In conclusion, there was a continuing rise in the annual incidence and prevalence of primary sclerosing cholangitis in Spain over a 5-year period.

Adolescent↗

Disulfiram-induced hepatitis. Report of four cases and review of the literature.

Liver test abnormalities following disulfiram therapy are common. However, overt disulfiram-induced hepatitis is rare but has a high mortality rate, specially when the etiologic role of disulfiram is not suspected and treatment is not discontinued. We report four cases of disulfiram-induced acute hepatitis with different degrees of severity and review the cases reported in the literature. The clinical spectrum of disulfiram hepatotoxicity ranges from minor elevation of serum aminotransferases to fulminant hepatitis. Although some patients with disulfiram-induced hepatitis have manifestations of hypersensitivity, recent clinical and experimental data suggest that disulfiram hepatotoxicity is produced by the accumulation of toxic metabolites.

Adult↗

Bone fractures in liver transplant patients.

Atraumatic bone fractures are a frequent complication in orthotopic liver transplantation (OLT). A retrospective study of 91 adult OLT patients was carried out to detect the prevalence of bone fractures, and to isolate predictive factors for their development. After OLT 22 patients (24%) developed 56 atraumatic bone fractures. All fractures occurred within the first 13 months following OLT. No predictive pre- or post-OLT risk factors for the development of bone fractures were identified.

Adult↗