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Biomedical subjects

P Escartín

Publications and source records attributed to P Escartín.

At least 19 recordsLinked to original sources

[Interferon, ribavirin and amantadine in prior nonresponders to interferon and ribavirin therapy with chronic hepatitis C (genotype 1)].

OBJECTIVE: Despite advances in the treatment of chronic hepatitis C virus (HCV), the disease persists after treatment with interferon and ribavirin in a large percentage of patients and other therapeutic options are lacking. We investigated the efficacy of retreatment with antiviral therapy including amantadine. EXPERIMENTAL DESIGN: prospective and open pilot study. PATIENTS: Thirty-nine patients with chronic HCV, genotype 1, who were nonresponders to interferon and ribavirin were included. The patients were given repeat treatment with interferon-alpha 2A (9 MU/week), ribavirin (1,000-1,200 mg/day) and amantadine (200 mg/day) for 48 weeks. RESULTS: HCV-RNA was undetectable in 5 patients in week 48 (12.8%) and in only 2 patients after 24 weeks of follow-up (5.1% of sustained responses). In patients with basal viremia of < 8 105 U/ml the probability of response at the end of treatment and of sustained response was 26.3 and 10.5%, respectively; in patients with elevated viremias response was 0%. CONCLUSIONS: In patients with chronic HCV genotype 1 without response to interferon and ribavirin, triple antiviral therapy with interferon, ribavirin and amantadine is not useful.

Adult↗

Time course of serum hepatitis C virus-RNA during chronic hepatitis C treatment accurately predicts the type of response.

AIM: To establish the value of alanine aminotransferase normalization and hepatitis C virus-RNA clearance as predictors of sustained virological response in naïve and relapser chronic hepatitis C patients on mono or combination therapy. METHODS: A total of 282 hepatitis C patients were studied: 98 naïves on interferon, and 64 naïves and 75 relapsers on interferon plus oral ribavirin; 45 patients were excluded. Drugs were administered at standard doses for 12 months. Alanine aminotransferase and hepatitis C virus-RNA were determined at baseline and at weeks 4, 12, 24, 48, and at 72 and 96 weeks after completion of therapy. RESULTS: The rate of sustained response was greater (P < 0.05) in naïves and relapsers on combination therapy (33% and 48%, respectively) than in naïves on interferon alone (16%). Hepatitis C virus-RNA significantly decreased from baseline by week 4 in naïves on interferon and relapsers on combination therapy and by week 12 in naïves on combination therapy. Alanine aminotransferase levels paralleled viremic load in naïves on interferon, yet in patients on combination therapy, alanine aminotransferase normalized independently of the virological response. During treatment, the main factor associated with sustained response was hepatitis C virus-RNA clearance by week 4 in naïves on interferon and relapsers on combination therapy, and by week 24 in naïves on combination therapy. CONCLUSION: Clearance of viraemia constitutes the best predictor of a sustained response to therapy, but needs to be measured at patient-specific times.

Adult↗

Improvement in liver fibrosis, functionality and hemodynamics in CCI4-cirrhotic rats after injection of the Liver Growth Factor.

BACKGROUND/AIMS: Most substances used in experimental models of cirrhosis are chosen either as protectors of lipid peroxidation, as antifibrogenic agents or as vitamins, among others. In this report, we analyze the improvement produced, in established cirrhosis (CCl4 plus phenobarbital) in rats, by intraperitoneal injection of Liver Growth Factor, a hepatic mitogen with activity both in vivo and in vitro. METHODS: Following confirmation of CCl4-induced cirrhosis, Liver Growth Factor (4.5 microg per ratx2 injections/week for 3 weeks) was administered to one group of rats (Cirr+LGF). The remaining rats (Cirr) received saline. The groups were compared in terms of serum enzymes, tissue damage, total liver collagen, collagenase activity, microsomal enzyme activities, splanchnic and systemic hemodynamics and portosystemic shunting. RESULTS: Treatment of rats presenting CCl4-induced cirrhosis with Liver Growth Factor decreased serum aminotransferase levels and increased levels of serum albumin and total protein. The Liver collagen content was lower in rats treated with Liver Growth Factor (2.96 vs. 4.32 mg/g liver, p<0.01). Microscopic studies revealed that the livers of rats receiving Liver Growth Factor showed decreases in fibrosis, necrosis and inflammatory infiltration, as well as a recovery of architectural integrity. Liver function was improved after treatment with Liver Growth Factor, as indicated by the rate constant for elimination of aminopyrine, which increased from 0.0063 to 0.0170 (p<0.05). This increase was accompanied by a higher total amount of cytochrome P-450 as well as of certain P-450 isoenzymes, especially those that are hormone-dependent, such as P-450 3A. The improved liver histology and function observed in Cirr+LGF rats was associated with decreases in portal pressure (14.4 vs. 9.4 mm Hg, p<0.01) and portosystemic shunting (55.8 vs. 11.5%, p<0.01), as well as increases in mean arterial pressure and systemic vascular resistance, and a reduction in ascites. CONCLUSIONS: Administration of the hepatic mitogen, Liver Growth Factor, to CCl4-cirrhotic rats decreased liver collagen and reorganized the hepatic extracellular matrix, resulting in an improvement in liver function, reduced portal pressure and amelioration of ascites.

Aminopyrine↗

Sustained response to interferon-alpha or to interferon-alpha plus ribavirin in hepatitis C virus-associated symptomatic mixed cryoglobulinaemia.

BACKGROUND: Hepatitis C virus (HCV) infection has been associated with mixed cryoglobulinaemia. AIM: To investigate the efficacy of anti-viral therapy on the eradication of HCV and its clinical manifestations in patients with HCV-associated symptomatic mixed cryoglobulinaemia. PATIENTS AND METHODS: 18 out of 32 patients with symptomatic mixed cryoglobulinaemia (MC group) received a 12-month course of interferon (3 MU three times a week, subcutaneously). Nonresponders or relapsers to this therapy were treated with interferon plus ribavirin (1200 mg/day, orally) for 12-months. 226 patients with HCV infection and without cryoglobulins were studied in comparison (Hepatitis C group). Serial quantification of serum HCV-RNA and cryoglobulins were performed. RESULTS: In the MC group, 10 out of 18 patients (55%) receiving interferon showed an end of treatment response, but at the end of follow-up, only five (28%) patients had a sustained response. In the hepatitis C group, 91 patients (47%) showed an end of treatment response but only 42 (20%) a sustained response. In the MC group alanine transaminase, cryocrit and rheumatoid factor decreased significantly in responders, with an improvement or disappearance of the MC-associated clinical manifestations. Alanine transaminase, cryocrit and rheumatoid factor increased in the relapsers and the clinical manifestations reappeared. Nonresponders and relapsers to interferon in the MC group were retreated with interferon plus ribavirin. Five out of eight nonresponders showed a end of treatment response but it was sustained in three of them. In the relapsers, treatment with combined therapy achieved a sustained response in four out of the five patients (80%). CONCLUSIONS: Interferon as monotherapy or combined with ribavirin is a safe and effective treatment in patients with HCV-associated MC. The presence of cryoglobulins does not affect the response to anti-viral treatment in patients with HCV infection. The eradication of HCV is associated with an improvement or disappearance of MC-associated clinical manifestations.

Antiviral Agents↗

Selective impairment of endothelium-mediated vasodilation in liver transplant recipients with cyclosporin A-induced hypertension.

Arterial hypertension is commonly observed in orthotopic liver transplantation (OLT) recipients receiving cyclosporin A (CsA), but the precise pathogenetic mechanisms remain partially unknown. The aim of this study was to investigate endothelium-dependent and -independent dilation and adrenergic constriction of resistance vessels of OLT recipients treated with CsA. Vascular reactivity was examined in 22 OLT patients, 10 with and 12 without arterial hypertension, and in 10 control subjects by assessing the forearm blood flow response to the brachial artery infusion of increasing concentrations of methacholine chloride, sodium nitroprusside, and phenylephrine. In 10 OLT patients, the response to methacholine was also examined after acetylsalicylate. The ratio of serum nitrite and nitrate to serum creatinine was lower (P < .05) in OLT patients with hypertension than in nonhypertensive patients and controls. Basal forearm flow was similar in the three groups. Methacholine vasodilation was impaired in the hypertensive patients as shown by a lower maximum forearm vasodilator response and a shift in the dose response curve to methacholine to the right compared with the nonhypertensive OLT patients and the controls. The response to methacholine was not modified after salicylate. Forearm flow response to nitroprusside was similar in the three groups. No differences between the patients and the controls were found in the maximum forearm flow contraction in response to phenylephrine. An impairment in endothelium-dependent vasodilation could mediate arterial hypertension in OLT patients immunosuppressed with CsA.

Adult↗

Propranolol plus prazosin compared with propranolol plus isosorbide-5-mononitrate in the treatment of portal hypertension.

BACKGROUND & AIMS: The association of prazosin to propranolol enhances the decrease in portal pressure but may cause hypotension and sodium retention. The aim of this study was to compare the portal pressure reduction and safety of the combination of propranolol plus prazosin with that of propranolol plus isosorbide-5-mononitrate (ISMN). METHODS: Fifty-six portal-hypertensive cirrhotics received randomly propranolol plus prazosin (n = 28) or propranolol plus ISMN (n = 28) orally for 3 months. Hemodynamics and liver and renal function were assessed at baseline and after 3 months. RESULTS: Propranolol plus prazosin caused a greater reduction in hepatic venous pressure gradient (HVPG) than propranolol plus ISMN (-24.2% +/- 11% vs. -16.1% +/- 11%; P < 0.01). A reduction in HVPG of > 20% was significantly more frequent in the propranolol plus prazosin group than in the propranolol plus ISMN group (85% vs. 53%; P < 0.05). Neither treatment modified hepatic blood flow, quantitative liver function test results, glomerular filtration rate, plasma renin activity, or plasma aldosterone level. Side effects occurred in 13 patients receiving propranolol plus prazosin compared with 7 receiving propranolol plus ISMN (P = 0.16). CONCLUSIONS: Propranolol plus prazosin has a greater portal pressure-lowering effect than propranolol plus ISMN. Both therapies were safe for liver and renal function. However, the combination of propranolol plus prazosin caused a greater decrease in arterial pressure and was less well tolerated than propranolol plus ISMN.

Adrenergic alpha-Antagonists↗

Accuracy of portal and forearm blood flow measurements in the assessment of the portal pressure response to propranolol.

BACKGROUND/AIMS: The portal pressure response to propranolol varies significantly in individual patients with cirrhosis. At present, propranolol responders can be identified only by measuring the hepatic venous pressure gradient. The aims of this study were: 1) to investigate whether the noninvasive monitoring of portal blood flow by pulsed Doppler ultrasound and forearm blood flow by strain-gauge plethysmography can predict the hepatic venous pressure gradient response to propranolol in patients with cirrhosis, and 2) to analyze the factors that may influence this response. METHODS: Hemodynamic measurements were undertaken in 80 patients with cirrhosis before and after receiving propranolol (0.15 mg/kg i.v., n = 60) or placebo (n = 20). RESULTS: No changes were observed in the placebo group. Propranolol lowered (p < 0.01) hepatic venous pressure gradient from 17.6 +/- 3.8 to 14.7 +/- 3.8 mmHg, portal blood flow from 1122 +/- 363 to 897 +/- 332 ml/min and forearm blood flow from 7.52 +/- 3.1 to 6.12 +/- 2.3 ml/min%. Changes in hepatic venous pressure gradient were correlated (p < 0.01) with those of portal blood flow (r = 0.82) and forearm blood flow (r = 0.54). The reduction in hepatic venous pressure gradient was > 20% in 23 patients ("responders"). The accuracy of portal Doppler flowmetry in identifying responders was higher than that of forearm plethysmography (88.3 vs. 68.3%, p < 0.05). Multivariate analysis proved that previous variceal bleeding was the only factor independently associated with a lack of response to propranolol (relative risk 3.42, 95% CI 1.5-7.4, p < 0.01). Hepatic venous pressure gradient reduction by propranolol was higher in non-bleeders than in bleeders (-19.9 +/- 9.4 vs. -11.3 +/- 8.6%, p < 0.01). CONCLUSIONS: Portal Doppler ultrasound can be used as a reliable surrogate indicator of the hepatic venous pressure gradient response to acute propranolol administration. In addition, our study indicates that this response is mainly influenced by previous variceal hemorrhage.

Adrenergic beta-Antagonists↗

Changes in gastrin and serum pepsinogens in monitoring of Helicobacter pylori response to therapy.

The aims of this study in 50 patients with H. pylori infection and duodenal ulcer were to examine the effect of eradication therapy on the serum levels of gastrin, pepsinogen I, and pepsinogen II and to investigate whether monitoring of the serum changes in these peptides after treatment could predict patient outcome. H. pylori status was assessed at entry and one and six months after therapy by culturing and microscopic analysis of the gastric mucosa and by [14C]urea breath test. Significant decreases were observed in the serum levels of gastrin (-11.4 +/- 3%), pepsinogen I (-28.9 +/- 4%), and pepsinogen II (-40.4 +/- 3%) in the 45 patients whose infection was eradicated, but not in the patients without eradication. Serum values of these peptides were unchanged in an additional group of 10 patients that only received omeprazol, none of whom had H. pylori eradicated. The best cutoff point of the percentage of each peptide to predict patient outcome was 10% for gastrin and pepsinogen I, and 15% for pepsinogen II. A pepsinogen II decrease > 15% resulted in the best marker of H. pylori clearance, accurately identifying patient outcome 86.6% of the time, whereas the diagnostic accuracy of gastrin and pepsinogen I was 61.7% and 76.6%, respectively. Significant correlations were found between the bacterial load assessed by histology with the serum concentrations of pepsinogen I and II and with the urease activity as measured by the amount of 14CO2 excreted. In conclusion, eradication of H. pylori infection is followed by a significant drop in serum levels of gastrin, pepsinogen I, and pepsinogen II. Changes in the latter are the most uniform and may be used as an indirect tool to predict treatment outcome.

Adult↗

Interferon and prednisone therapy in chronic hepatitis C with non-organ-specific antibodies.

BACKGROUND/AIMS: The relationship between hepatitis C virus and autoimmunity is controversial. The issue is particularly relevant in those patients with hepatitis C virus infection and serum autoantibodies in whom steroids can exacerbate viral replication and interferon can lead to decompensated liver disease. The aim of this study was to evaluate the response to a course of prednisone or interferon-alpha 2b. METHODS/RESULTS: The 12 study patients had biopsy-proven chronic hepatitis, serum HCV-RNA (by nested polymerase chain reaction) and non-organ-specific antibodies (eight with liver and kidney microsomal antibodies and four with antinuclear antibodies). Eight of these 12 patients received a 4-month course of prednisone (0.5 mg/kg per day), which increased alanine aminotransferase (mean +/- SE) (174 +/- 31 vs 252 +/- 18 U/l, p < 0.05) and bilirubin levels (0.96 +/- 0.17 vs 1.42 +/- 0.18 mg/dl, p = 0.09), without changing liver histology (Knodell index, 13.6 +/- 0.4 vs 13.1 +/- 0.3). Subsequent treatment with interferon in the 12 patients reduced serum alanine aminotransferase levels (170 +/- 20 vs 41 +/- 7 U/l, p < 0.0001) and portal and lobular inflammation (Knodell index, 13.8 +/- 0.5 vs 8.4 +/- 0.2, p < 0.001). A complete response to interferon was observed in ten of these patients (83%), eight of whom had previously been treated with prednisone. Serum HCV-RNA level decreased in interferon responders. A sustained response 1 year after withdrawal of interferon was seen in only five patients (41%). CONCLUSIONS: Patients with chronic hepatitis C and autoantibodies show a favorable response to interferon, but not to prednisone. The latter regimen can exacerbate liver necrosis in these subjects. The presence of autoantibodies in hepatitis C patients does not modify the response to interferon.

Adult↗

Continuous prazosin administration in cirrhotic patients: effects on portal hemodynamics and on liver and renal function.

BACKGROUND & AIMS: Hepatic vascular resistance is influenced by alpha-adrenergic tone. The aim of this study was to investigate the effects of continuous blockade of alpha-adrenoceptors with prazosin on hemodynamics, liver function, and renal function and whether the association of propranolol or furosemide enhances the portal pressure lowering effect of prazosin. METHODS: Cirrhotic patients with portal hypertension were studied at baseline and after a 3-month course of prazosin (n = 18) or placebo (n = 10). RESULTS: No changes were observed in the placebo group. Prazosin decreased the hepatic venous pressure gradient (HVPG) while increasing hepatic blood flow. Liver function improved as shown by an increase in hepatic and intrinsic hepatic clearances of indocyanine green and galactose elimination capacity. A significant reduction in mean arterial pressure and systemic vascular resistance was associated with increases in plasma renin activity and aldosterone concentration and a decrease in glomerular filtration rate. The plasma volume increased significantly, and 6 patients developed edema. The association of propranolol (n = 8) but not furosemide (n = 7) to prazosin increased the reduction in HVPG and attenuated the increase in plasma renin activity. CONCLUSIONS: In cirrhotic patients, continuous prazosin administration reduces portal pressure and improves liver perfusion and function but favors sodium and water retention. The association of propranolol enhances the decrease in portal pressure, suggesting a potential benefit from this combined therapy.

Adrenergic alpha-Antagonists↗

Enhanced endothelium-dependent vasodilation in patients with cirrhosis.

Experimental evidence indicates that an increased production of nitric oxide could play a role in the peripheral vasodilation of portal hypertension. To test this hypothesis in humans, we studied basal serum NO(2-) + NO3- levels and the response of forearm resistance vessels to increasing concentrations of methacholine chloride, sodium nitroprusside, and phenylephrine infused into the brachial artery of 12 cirrhotic patients and 10 controls. Forearm vascular resistance (FVR) was calculated from mean arterial pressure and forearm blood flow (FBF). Cirrhotics showed higher NO(2-) + NO3- levels (P < 0.05), higher FBF (P < 0.01), and lower FVR (P < 0.01) than controls. The reduction of FVR in response to every dose of methacholine was greater in cirrhotics than in controls; this was significant (P < 0.05) at the 3 and 10 micrograms/min doses. This response to methacholine was not modified by blockade of vascular prostacyclin. The response to nitroprusside was similar in both groups. The increase in FVR in response to every dose of phenylephrine was significantly (P < 0.01) lower in cirrhotics than in controls. In cirrhotics, a significant correlation (r = -0.81, P < 0.01) was found between the FVR response to the highest doses of methacholine and phenylephrine. In conclusion, cirrhotic patients show an enhanced endothelium-mediated vasodilation, which suggests an increased synthesis of nitric oxide. This defect may mediate the peripheral vasodilation and hyporeactivity to vasopressors of these patients.

Adult↗

Octreotide prevents postprandial splanchnic hyperemia in patients with portal hypertension.

An increase in splanchnic blood flow is a physiological response to food intake. In patients with cirrhosis whose hepatic vascular resistance is already high, this increase in flow leads to marked increases in portal pressure. This study investigates whether octreotide prevents the increases in hepatic flow and portal pressure that follow the ingestion of a meal in patients with cirrhosis. Twenty-two patients with cirrhosis and portal hypertension were randomized to receive a mixed liquid meal (520 kcal) plus a single subcutaneous injection of either placebo or octreotide (200 micrograms). In the placebo group the ingestion of a meal was followed by an increase in the hepatic venous pressure gradient (+ 19.4 +/- 4.3%, p < 0.01) and hepatic blood flow (+ 38.2 +/- 14.6%, p < 0.05) at 30 min. In contrast, in the octreotide group eating caused no significant change in the hepatic venous pressure gradient (-2.8 +/- 3.6%, NS), while hepatic flow was decreased (-6.08 +/- 5.4%, p < 0.05). Octreotide blunted the postprandial increase in serum insulin and glucagon levels observed in the placebo group. In conclusion, in patients with cirrhosis and portal hypertension, octreotide prevents the postprandial increase in hepatic blood flow, and consequently also in portal pressure. These findings suggest that this drug could play a role in the long-term management of portal hypertension.

Blood Glucose↗

The use of the Dornier MPL-9000 lithotripter in the treatment of gallbladder and renal stones. Early experience.

The experience of two units (Gastroenterology and Urology) of Clínica La Luz, Madrid, in the treatment of gallbladder and renal lithiasis using the Dornier MPL-9000 lithotripter is reported herein. This lithotriptor has been utilized in the treatment of all cases of gallbladder calculi for which it is indicated and renal calculi localized high up (kidney), and in those cases that are difficult to treat with other lithotriptors such as patients with kyphoscoliosis, radiolucent calculi, elderly patients, children, etc.). During the first year the gallstone lithotripsy unit was utilized, 401 patients were referred for treatment. Of these, 180 met the criteria for patient selection. (Over 360 have been treated to date.) Sixty of these 180 patients had a single gallstone of up to 2.5 cm. These 60 patients were selected for the study since they comprised a group where the best results could be expected. The aim of studying this patient group was to evaluate the results achieved by lithotripsy and the short and medium-term outcome in this ideal group of patients. Concerning renal lithiasis, these are the first 100 cases treated with the MPL-9000 (currently over 420 have been treated). Eighty cases had a single calculus (60 caliceal and 20 pyelic), 15 had multiple calculi, and 5 had a staghorn stone. Treatment for gallbladder and renal lithiasis was exclusively by shock waves; i.e., as monotherapy with no other auxiliary procedure. The average number of shock waves used was 2,350 with a mean kV of 18 for gallbladder lithiasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Extracorporeal biliary lithotripsy: results in 60 cases of single calculus].

The outcome of 60 cases of single biliary stone with a maximum diameter of 25 mm was evaluated. The patients were symptomatic, with functioning gallbladder, and were selected from a group of 180 to evaluate the effects of electrohydraulically generated shockwaves on a priori ideal cases for this procedure. In seven patients fragmentation was not achieved, probably because of the pigmentary character of the stone, that was later verified at cholecystectomy. In 20 out of the 53 in whom fragmentation was satisfactory (38%), fragments were not observed after 24 hours. 32 patients (54%) had a stone-free gallbladder 3 months afterwards; at six months, the number had increased to 40 (66%). This rate becomes 77% if only the cases with fragmentation are considered. In 29% of patients episodes of colicky biliary pain developed as complication. No case of pancreatitis or stuck in gallstone were observed. We conclude that shock waves appear as an excellent therapeutic alternative in single gallstones up to 25 mm in size.

Adult↗

Ascitic fluid polymorphonuclear cell count and serum to ascites albumin gradient in the diagnosis of bacterial peritonitis.

The analysis of ascitic fluid has been complicated by several recently reported new tests. To simplify this assessment, we evaluated nine parameters prospectively and simultaneously in blood and ascitic fluid from 285 patients with ascites to determine which were the most reliable for immediate diagnosis of the etiology of the ascites and of its complications. Subjects were first divided into four groups: sterile cirrhotic ascites (n = 201), spontaneous bacterial peritonitis (n = 41), malignant ascites (n = 34), and miscellaneous ascites (n = 9). An ascitic fluid polymorphonuclear count greater than 500/microliters was the test with the greatest accuracy (96%) for the diagnosis of spontaneous bacterial peritonitis. Neither the most precise cutoff values for ascitic fluid pH (less than 7.32) and ascitic fluid lactate (greater than 32 mg/dl), nor their respective blood-ascitic fluid gradients (greater than 0.11 and less than -20 mg/dl) were more reliable indexes of spontaneous bacterial peritonitis, mainly due to the decreased ascitic fluid pH and increased ascitic fluid lactate observed in malignant ascites, tuberculous peritonitis, and pancreatic ascites. A blood-ascitic fluid albumin gradient less than 1.1 g/dl was the most accurate parameter for the diagnosis of malignant ascites (diagnostic efficacy, 93%). Therefore, the etiologic analysis of ascitic fluid might be simplified and the single practice of two tests, ascitic fluid polymorphonuclear cell count and blood-ascitic fluid albumin gradient, provides immediately useful information.

Adult↗