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The effects of octreotide on postprandial hemodynamic responses were evaluated in 20 patients with postnecrotic cirrhosis. They were randomly assigned to receive either a 100-micrograms bolus with a 100-micrograms/h infusion of octreotide or a placebo. Placebo administration did not affect any of the hemodynamic values. However, after a liquid meal of 500 kcal, postprandial increases in the hepatic venous pressure gradient and hepatic blood flow were observed in patients receiving placebo, while the systemic hemodynamic values remained unchanged. In contrast, in patients receiving octreotide, the hepatic blood flow was significantly decreased 30 min after administration, while the hepatic venous pressure gradient and the systemic hemodynamic values were not affected. After ingestion of a meal, the mean values of the hepatic blood flows were not significantly different from basal values. Moreover, the wedged hepatic venous pressure, the hepatic venous pressure gradient and the systemic hemodynamic values were not affected by meal ingestion. However, during octreotide infusion, hepatic blood flow 30 min after the meal had a tendency to increase compared to before the meal. In conclusion, octreotide inhibited the postprandial increase in portal pressure in patients with postnecrotic cirrhosis. In addition, octreotide decreased hepatic blood flow in the fasting state. When given before a meal, the increase in blood flow induced by the meal restored the hepatic blood flow to basal levels.

Aliskiren is a direct renin inhibitor used in the treatment for arterial hypertension. It can also augment nitric oxide (NO) production, which plays a crucial role in the pathogenesis of portal hypertension and modulation of porto-systemic collaterals. This study investigated the effects of aliskiren on portal pressure and porto-systemic collaterals of portal vein-ligated (PVL) rats.Sham-operated and PVL rats received aliskiren (50 mg/kg per day) or distilled water (control) treatment for 10 days. The mean arterial pressure and portal pressure were measured by catheterization of the right femoral artery and mesenteric vein, while the superior mesenteric arterial blood flow was measured by Doppler technique. The left adrenal vein and superior mesentery artery were dissected for mRNA study. The PVL rats also underwent preincubation with (i) Krebs solution (control); (ii) 10(-4) M aliskiren; or (iii) 10(-4) M aliskiren plus nonselective NO inhibitor N(ω)-nitro-L-arginine (10(-4) M), followed by the addition of arginine vasopressin (AVP) to evaluate the collateral vascular responsiveness.Aliskiren had systemic arterial pressure- and portal pressure-lowering effects in PVL rats. Superior mesentery arterial resistance also decreased. The constitutive NO synthase was enhanced in the left adrenal vein and superior mesentery artery after aliskiren treatment. Aliskiren attenuated the collateral vasoconstrictive effects of AVP, but the vasodilatory effects were abolished after nonselective NO synthase inhibition.Chronic aliskiren use reduces portal pressure in portal hypertensive rats partly due to the modulation of splanchnic and collateral NO synthase.

Nitric oxide (NO) inhibition aggravates hepatic damage and encephalopathy and increases mortality in rats with thioacetamide (TAA)-induced acute liver failure. Statins enhance NO production but whether they influence the above parameters are unknown.Male Sprague-Dawley rats were used. In the first series, TAA (350 mg/kg per day, i.p. for 3 days) was administered to induce acute liver failure. Control rats received saline. Rats received distilled water or pravastatin (20 mg/kg per day, p.o.) from 2 days before to 3 days after TAA or saline injection. In the second series, liver cirrhosis was induced by common bile duct ligation (BDL). Sham-operated rats served as controls. Rats received distilled water or pravastatin for 5 or 14 days until the 42nd day after operation. On the last day of treatment, survival, motor activities, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, ammonia and brain histology were evaluated.Thioacetamide and BDL rats showed higher ALT, AST, bilirubin and ammonia levels and lower motor activity counts compared with their corresponding control groups. In TAA rats, pravastatin elicited higher total and ambulatory motor activity counts and lower AST and total bilirubin levels. Survival was improved, whereas brain HE staining was not significantly different in TAA rats with or without pravastatin treatment. In BDL groups, rats with or without pravastatin treatment were not different in motor activity counts and liver biochemistry.Pravastatin ameliorates hepatic encephalopathy and liver biochemistry and improves survival in rats with acute liver failure, but not in those with cirrhosis.

Gastro-oesophageal variceal haemorrhage is one of the most dreadful complications of portal hypertension and can be controlled with vasoconstrictors. Nevertheless, sympathetic tone abnormality and vascular hyporesponsiveness in portal hypertension may impede the haemostatic effects of vasoconstrictors. Propranolol, a β-blocker binding the G-protein-coupled adrenoceptor, is a portal hypotensive agent. However, whether propranolol influences the collateral vasoresponse is unknown. Portal hypertension was induced by PVL (portal vein ligation) in Sprague-Dawley rats. In an acute study with an in situ perfusion model, the collateral responsiveness to AVP (arginine vasopressin) was evaluated with vehicle, propranolol (10 μmol/l), propranolol plus suramin (100 μmol/l, a G(α) inhibitor) or suramin pre-incubation. G(α) mRNA expression in the splenorenal shunt, the most prominent intra-abdominal collateral vessel, was measured. In the chronic study, rats received DW (distilled water) or propranolol (10 mg x kg(-1) of body weight x day(-1)) for 9 days. Then the concentration-response relationship of AVP and G(α) mRNA expression were assessed. Propranolol pre-incubation elevated the perfusion pressure changes of collaterals in response to AVP, which was inhibited by suramin. The splenorenal shunt G(αq) and G(α11) mRNA expression were enhanced by propranolol. The group treated with propranolol plus suramin had a down-regulation of G(α11) as compared with the propranolol group. Chronic propranolol treatment reduced mean arterial pressure, PP (portal pressure) and the perfusion pressure changes of collaterals to AVP. G(αs) expression was up-regulated. In conclusion, propranolol pre-incubation enhanced the portal-systemic collateral AVP responsiveness in portal hypertensive rats, which was related to G(αq) and G(α11) up-regulation. In contrast, the attenuated AVP responsiveness by chronic propranolol treatment was related to G(αs) up-regulation. The G(α) signalling pathway may be a therapeutic target to control variceal bleeding and PP in portal hypertension.

Background/Aims:In liver cirrhosis/portal hypertension, collaterals as varices may bleed and are influenced by vasoresponsiveness. An angiotensin blockade ameliorates portal hypertension but the influence on collaterals is unknown. Methods:Portal hypertension and cirrhosis were induced by portal vein (PVL) and common bile duct ligation (BDL). Hemodynamics, real-time PCR of angiotensin II receptors (AT1R, AT2R) in the left adrenal vein (LAV, sham) and splenorenal shunt derived from LAV (PVL, BDL) were performed. With an in situcollateral perfusion model, angiotensin II vasoresponsiveness with different preincubations was evaluated: (1) vehicle; (2) AT1R blocker losartan; (3) losartan plus nonselective nitric oxide synthase (NOS) inhibitor (Nω-nitro-L-arginine); (4) AT2R blocker PD123319; (5) PD123319 plus Nω-nitro-L-arginine; (6) Nω-nitro-L-arginine, and (7) losartan plus inducible NOS inhibitor aminoguanidine. Results: LAV AT1R and AT2R expression decreased in PVL and BDL rats. Losartan attenuated angiotensin II-elicited vasoconstriction but PD123319 had no effect. Nω-nitro-L-arginine but not aminoguanidine reversed the losartan effect. Conclusions:Angiotensin receptors are downregulated in the collateral vessel of portal hypertensive and cirrhotic rats. The AT1R blockade attenuates the angiotensin II vasoconstrictive effect, suggesting AT1R mediates collateral vasoconstriction and the influence of AT2R is negligible. The lack of aminoguanidine influence indicates that endothelial NOS participates in the losartan effect.

Background Liver functions and portosystemic collaterals influence the development and severity of hepatic encephalopathy (HE) in cirrhosis. However, it has not been examined which factor has a greater influence or if shunts can be used to determine the presence and severity of HE. The expression of tumor necrosis factor-α (TNF-α) is increased in cirrhosis, and its role in HE deserves further evaluation. Methods Portal hypertension was induced by portal vein ligation (PVL; a model of high-degree portosystemic shunting without significant liver damage) and liver cirrhosis was induced by bile duct ligation (BDL; a model of low-degree shunting with liver cirrhosis) in male Spraque-Dawley rats. Sham-operated rats were used as controls. Motor activity counts, hemodynamic parameters, plasma levels, liver biochemistry parameters, TNF-α, and a flow-pressure curve study of portosystemic collaterals (where a higher slope indicates fewer portosystemic collaterals) were performed on Day 7 after PVL and Week 5 after BDL. Results Portal pressure was significantly higher in the PVL and BDL groups than in controls. The liver biochemistry parameters, TNF-α, and motor activities were not significantly different between the PVL and PVL-control groups. In the BDL group, TNF-α, AST, and total bilirubin levels were significantly higher and the motor activity counts were lower than in the BDL-control group. Moreover, in the BDL rats, TNF-α ( p =0.037, R=-0.490), AST ( p =0.007, R=-0.595) and total bilirubin (P=0.001, R=−0.692) levels, but not the slopes of the flow-pressure curves, were significantly and negatively correlated with the motor activity counts. Conclusion The presence of a high degree of portosystemic shunting without significant liver damage may not be adequate for the development of HE.

The pressure of oesophageal varices was determined by fine needle direct puncture in 19 patients with hepatitis B surface antigen (HBsAg)-positive cirrhosis after the first episode of variceal bleeding before endoscopic sclerotherapy. Both the stability and reliability of the measurement of intravariceal pressure by fine needle puncture were confirmed. Seven patients received intravenous 1 mL normal saline. Intravariceal pressure did not change before and after injection of normal saline (16.3 +/- 4.0 vs 16.0 +/- 4.0 mmHg, P > 0.05). Twelve patients received intravenous 1 units vasopressin and this caused a significant reduction in intravariceal pressure (15.6 +/- 2.6 vs 10.3 +/- 2.9 mmHg, P < 0.0001). The average basal intravariceal pressure in these patients was 15.8 +/- 3.1 mmHg. After intravariceal pressure was recorded, the needle was left in situ and endoscopic sclerotherapy commenced immediately. During the investigation, no adverse reaction or complication was encountered. It was concluded that the measurement of intravariceal pressure by fine needle direct puncture followed by immediate sclerotherapy is a safe and simple method to evaluate the short-term effect of drug prevention from oesophageal variceal bleeding and that vasopressin causes reduction of intravariceal pressure.

Portal-systemic collateral vascular resistance and vasoconstrictor responsiveness are crucial in portal hypertension and variceal bleeding control. Statins enhance vasodilators production, but their influence on collaterals is unknown. This study aimed to survey the effect of simvastatin on collaterals.Partially portal vein-ligated rats received oral simvastatin (20 mg/kg/day) or distilled water from -2 to +7 day of ligation. After hemodynamic measurements on the eighth postoperative day, baseline perfusion pressure (i.e. an index of collateral vascular resistance) and arginine vasopressin (AVP, 0.1 nM-0.1 microM) responsiveness were evaluated with an in situ perfusion model for collateral vascular beds. RT-PCR of endothelial NO synthase (eNOS), inducible NOS (iNOS), cyclooxygenase-1 (COX-1), COX-2, thromboxane A(2) synthase (TXA(2)-S) and prostacyclin synthase genes was performed in parallel groups for splenorenal shunt (SRS), the most prominent intra-abdominal collateral vessel. To determine the acute effects of simvastatin, collateral AVP response was assessed with vehicle or simvastatin. SRS RT-PCR of eNOS, iNOS, COX-1, COX-2 and TXA(2)-S, and measurements of perfusate nitrite/nitrate, 6-keto-PGF1(alpha) and TXB(2) levels were performed in parallel groups without AVP.Acute simvastatin administration enhanced SRS eNOS expression and elevated perfusate nitrite/nitrate and 6-keto-PGF1(alpha) concentrations. Chronic simvastatin treatment reduced baseline collateral vascular resistance and portal pressure and enhanced SRS eNOS, COX-2 and TXA(2)-S mRNA expression. Neither acute nor chronic simvastatin administration influenced collateral AVP responsiveness.Simvastatin reduces portal-systemic collateral vascular resistance and portal pressure in portal hypertensive rats. This may be related to the enhanced portal-systemic collateral vascular NO and prostacyclin activities.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor can enhance endothelial nitric oxide synthase expression and induce vasodilatation. The vasodilatory effect may be detrimental to portal-systemic collaterals due to aggravating the shunting degrees. The present study investigated the effects of pravastatin, a HMG-CoA reductase inhibitor, on the collateral vascular responsiveness to endothelin-1 (ET-1) and portal-systemic shunting in portal hypertensive rats.The partial portal vein-ligated (PVL) rats received either pravastatin (25 mg/kg per day) or distilled water since 2 days prior to until 7 days after ligation. On the 8(th) day following hemodynamic measurements, the collateral vascular responsiveness to ET-1 was evaluated by an in situ collateral perfusion model. The shunting degrees of collaterals were evaluated by constructing vascular flow-pressure curves and color microsphere study, respectively. PVL rats underwent pre-incubation with: (i) Krebs solution (control); or Krebs solution plus (ii) 2 x 10(-5) M pravastatin; (iii) pravastatin + N(omega)-nitro-L-arginine (10(-4) M); and (iv) pravastatin + indomethacin (10(-5) M), followed by ET-1 (10(-10)-10(-7) M) administration to evaluate the collateral vascular responsiveness.In chronic study, pravastatin did not modify systemic and portal hemodynamics and collateral vascular responsiveness to ET-1. The resistances of flow-pressure curves and the microsphere study demonstrated similar shunting degrees between both groups. Furthermore, pravastatin pre-incubation didn't reduce collateral perfusion pressure to ET-1.Chronic pravastatin administration does not induce detrimental effects on hemodynamics and collaterals in PVL rats, nor does it influence the shunting degree. In addition, it does not modify the vasoconstrictive effect of ET-1 on the collaterals of PVL rats.

Inflammation plays a pivotal role in liver injury. Gabexate mesilate (GM, a protease inhibitor) inhibits inflammation by blocking various serine proteases. This study examined the effects of GM on hepatic encephalopathy in rats with acute and chronic liver failure.Acute and chronic liver failure (cirrhosis) were induced by intraperitoneal TAA administration (350 mg/kg/day for 3 days) and common bile duct ligation, respectively, in male Sprague-Dawley rats. Rats were randomized to receive either GM (50 mg/10 mL/kg) or saline intraperitoneally for 5 days. Severity of encephalopathy was assessed by the Opto-Varimex animal activity meter and hemodynamic parameters, mean arterial pressure and portal pressure, were measured (only in chronic liver failure rats). Plasma levels of liver biochemistry, ammonia, nitrate/nitrite, interleukins (IL) and tumor necrosis factor (TNF)-alpha were determined.In rats with acute liver failure, GM treatment significantly decreased the plasma levels of alanine aminotransferase (P = 0.02), but no significant difference of motor activity, plasma levels of ammonia, IL-1beta, IL-6, IL-10 and TNF-alpha or survival was found. In chronic liver failure rats, GM significantly lowered the plasma TNF-alpha levels (P = 0.04). However, there was no significant difference of motor activity, other biochemical tests or survival found. GM-treated chronic liver failure rats had higher portal pressure (P = 0.04) but similar mean arterial pressure in comparison with saline-treated rats.Chronic GM treatment does not have a major effect on hepatic encephalopathy in rats with TAA-induced acute liver failure and rats with chronic liver failure induced by common bile duct ligation.

To evaluate the role of hepatitis C virus (HCV) in Chinese patients with hepatocellular carcinoma (HCC), the antibodies to HCV (anti-HCV) were detected by enzyme immunoassay in 41 (12.6%) of the 326 patients with HCC. However, none of 35 patients with metastatic carcinoma of the liver had detectable anti-HCV. The prevalence of anti-HCV was significantly higher in patients with hepatitis B surface antigen (HBsAg)-negative HCC than those with HBsAg-positive HCC (37.3% versus 4.1%, P < 0.0001). However, the prevalence of anti-HCV was much higher in patients with HCC with negative results for HBsAg and antibody to hepatitis B core antigen (54.5%). The mean age of patients with HCC with positive results for anti-HCV was significantly greater than that of patients with HBsAg-positive HCC (65.1 versus 55.5 years, P c 0.0001). Alpha-fetoprotein levels greater than 20 ng/ml were found in 70.7% of patients with HCC with positive results for anti-HCV and in 73.3% of patients with HBsAg-positive HCC. Of the Chinese patients with HCC, 74.5% had HBsAg-positive results and 96.6% had positive results for antibody to hepatitis core antigen. These data indicate that, although HCV may play an etiologic role in HCC, hepatitis B virus is still the most important causal agent among most Chinese patients with HCC. Cancer 1992: 69:342-345.

The portal hypotensive effect of vasopressin during hemorrhage is less effective than that during stable condition in cirrhotic patients or experimental portal hypertension (the so-called hyposensitivity phenomenon). Recent studies have demonstrated that constitutive nitric oxide activities and bradykinin in hemorrhage-transfused partially portal vein-ligated rats are responsible, at least partly, for the splanchnic hyposensitivity to glypressin (a long acting vasopressin analogue). This study investigated the relative contribution of nitric oxide synthase isoforms and the role of bradykinin in the pathogenesis of splanchnic hyposensitivity in rats with cirrhosis induced by common bile duct-ligation (BDL).Five weeks after BDL, systemic and portal hemodynamics were measured in stable or bleeding BDL rats receiving intravenous infusion of glypressin (0.2 mg/kg). In the treatment groups, N(G)-nitro-L-arginine methyl ester (L-NAME, a non-selective nitric oxide synthase inhibitor), L-canavanine (a specific inducible nitric oxide synthase inhibitor) or HOE 140 (a bradykinin B2 receptor antagonist) was administered 45 minutes before the infusion of glypressin. In rats with a hypotensive hemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin or various inhibitors.Splanchnic hyposensitivity to glypressin was demonstrated in the hemorrhage-transfused BDL rats. The infusion of L-NAME elevated the mean arterial pressure in the bleeding BDL rats without the modulation of portal pressure. The addition of L-NAME or HOE 140, but not L-canavanine, significantly and similarly potentiated the portal-hypotensive effects of glypressin.Constitutive nitric oxide synthase and bradykinin play major roles in the development of splanchnic hyposensitivity to glypressin observed in hemorrhage-transfused rats with biliary cirrhosis.

Cirrhotic patients with portal hypertension and variceal hemorrhage are vulnerable to endotoxemia. However, the direct influence of endotoxemia on portal-systemic collateral vasculature remains unexplored. In this study, portal hypertension was induced in Sprague-Dawley rats by partial portal vein ligation. On the 7th day after portal vein ligation, at 0.5, 1.5, and 5 h post endotoxin (LPS; Escherichia coli serotype O111:B4, 3 mg/kg, i.p., E0.5, E1.5 and E5, respectively) or saline (control, C0.5, C1.5, and C5, respectively) injection, hemodynamic measurements and concentration-response relationships to arginine vasopressin (AVP; 10(-10)-10(-7) mol/L) in collateral vascular bed were obtained. In another six parallel groups, reverse-transcriptase-polymerase chain reaction of iNOS, eNOS, and endothelin 1 (ET-1) mRNA expressions for splenorenal shunt, the most prominent intra-abdominal collateral vessel, was performed. The results showed that E0.5 had lower perfusion pressure changes to AVP and higher splenorenal shunt eNOS expression than C0.5 group (P < 0.05). Compared with C1.5, tachycardia, higher perfusion pressure changes and enhanced splenorenal shunt iNOS and ET-1 expression were observed in E1.5 group (P < 0.05). In E5, systemic and portal hypotension with markedly enhanced collateral AVP responsiveness and splenorenal shunt iNOS and ET-1 expressions were noted (P < 0.05). In conclusion, vasoactive substances counterregulation participates, at least in part, the time-dependent changes of collateral AVP responsiveness in endotoxemic portal hypertensive rats.

It has been suggested that vasopressin given during hemorrhage may be less effective than when given during a stable state in a portal-hypertensive rat model. This study was designed to evaluate the hemodynamic response to vasopressin infusion in 25 HBsAg-positive cirrhotic patients. Nine patients had active variceal hemorrhage before vasopressin infusion, and the other 16 patients were in a stable condition at the time of infusion. The two groups of patients were similar in baseline values except that a higher heart rate was found in patients with hemorrhage (96 +/- 20 vs. 73 +/- 10 beats/min, mean +/- S.D., p less than 0.01). Thirty minutes after vasopressin infusion (0.66 units/min), hepatic venous pressure gradient significantly decreased in both bleeding and stable patients (from 21 +/- 9 to 18 +/- 9 mm Hg, p less than 0.05; and from 18 +/- 4 to 8 +/- 3 mm Hg, p less than 0.0001, respectively). However, the decrease of hepatic venous pressure gradient was less obvious in bleeding patients as compared with stable patients (4 +/- 3 vs. 9 +/- 2 mm Hg, p less than 0.0001). A significant reduction of hepatic venous pressure gradient after vasopressin infusion was found in five bleeding patients without shock (from a median of 16 mm Hg [range = 12 to 26] to 11 mm Hg [range = 6 to 18], p less than 0.05), but not in four bleeding patients with shock (from 28 [range = 15 to 36] to 25 [range = 18 to 33] mm Hg, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

In an attempt to evaluate the effect of quinidine in the treatment of patients with cirrhosis and muscle cramps, 31 cirrhotic patients with muscle cramps were randomly divided into two groups and given orally 400 mg of quinidine sulfate per day or placebo, respectively. Baseline clinical and laboratory data for these two groups were similar. Four weeks after oral administration of quinidine, the number of cramps significantly decreased from 14.4 +/- 1.7 (mean +/- S.E.) to 4.4 +/- 1.1 episodes (p less than 0.0001), but it remained unchanged in the placebo group (from 11.8 +/- 1.0 to 11.5 +/- 1.5 episodes, p greater than 0.05). In addition, 88% of the 16 patients on quinidine and 13% of the 15 patients on a placebo showed a greater than 50% reduction in the number of cramps during a 4-week treatment period (p less than 0.0001). The peak and trough serum levels of quinidine in patients having received quinidine for 2 weeks were 1.3 +/- 0.1 and 0.7 +/- 0.1 mg/l, respectively. There was a significant relationship between serum quinidine concentrations and attenuation of cramps. No significant adverse effect was observed during the study, except for five (31%) patients who developed mild diarrhea after quinidine therapy. Diarrhea subsided spontaneously or was controlled by medications without the interruption of quinidine therapy. It was concluded that quinidine is a safe and effective drug for the treatment of cirrhotic patients with muscle cramps.

Tumor necrosis factor-alpha (TNFalpha) has been reported to be associated with insulin resistance and induce inflammatory cytokines formation. Previous studies in human and animals showed inhibition of TNF-alpha improved severity of non-alcoholic fatty liver disease (NAFLD). The aims of this study were to measure plasma levels of TNFalpha in NAFLD and healthy subjects and investigate potential risk factors.A total of 144 patients (90 NAFLD, 50 controls) were enrolled. Clinical and laboratory data of each patient were collected. Plasma levels of TNF-alpha were measured with a commercially available solid phase sandwich enzyme-linked immunosorbent assay (RD systems, USA). The lower detection limit of this assay was 0.12 pg/mL.Multivariate analyses showed elevated triglyceride (odds ratio: 7.30, p0.001) and BMI25 kg/m2 (odds ratio: 3.57, p0.005) were the two factors associated with NAFLD. Mean plasma level of TNF-alpha was significantly higher in NAFLD patients with abnormal ALT than controls (2.63+/-0.44 pg/mL vs. 1.56+/-0.10 pg/mL, p=0.016). Modest correlations were noted between plasma levels of TNF-alpha with ALT (r=0.25, p0.005) and triglyceride (r=0.40, p0.001).TNF-alpha may participate in the pathogenesis of NAFLD. Inhibition of TNF-alpha activity by drugs or antibodies may be a potential approach to treat NAFLD patients.

NAFLD with pathological features resembles alcohol-induced liver injury but its pathogenesis remained unclear. IL-6 and IL-8 belonged to pro-inflammatory cytokines and previous studies in alcoholic liver disease showed plasma levels of IL-6 and IL-8 correlated with disease severity. There has been no report regarding plasma levels of IL-6 and Il-8 in Chinese patients with NAFLD.A total of 94 NAFLD patients and 50 age and sex-matched control subjects were enrolled to compare the clinical characteristics and plasma levels of IL-6/IL-8. IL-6 and IL-8 were determined by commercially available enzyme-linked immunosorbent assay (RD systems, USA).As compared with control group, NAFLD patients had significantly higher BMI (p0.001), fasting sugar (p=0.002), cholesterol (p=0.017), and triglyceride (p0.001) level. NAFLD patients with abnormal ALT had the highest plasma levels of IL-6 but it did not reach the statistical differences as compared with other groups. Plasma IL-8 measurement showed NAFLD patients with abnormal serum ALT had the highest level (42.87+/-16.58 pg/mL), followed by NAFLD with normal ALT (13.53+/-2.32 pg/mL) and control groups (9.19+/-1.75 pg/mL, p=0.028 as compared with NAFLD with abnormal ALT).Through the chemotactic and proinflammatory effects, IL-8 may play a role in the pathogenesis of NAFLD in Chinese patients.

Focal hepatic fatty infiltration may be mistaken for hepatic neoplasm on ultrasonography. A sonographic feature mimicking "space occupying lesions" was identified in 41 cases with focal fatty liver, which led to the recognition of four sonographic patterns: (1) Ten patients in whom the livers were characterized by irregular configurations of hyperechoic and hypoechoic areas. Although confusing to inexperienced sonographers, all of them were properly interpreted by experienced sonographers. (2) One patient in whom the hepatic sonography revealed a hyperechoic nodule, but which was correctly diagnosed by computed tomography (CT) scan. (3) Six patients in whom the livers were characterized by multiple confluent hyperechoic lesions, which were all misinterpreted by sonographers and misinterpreted following CT scans in 4 cases and angiography in 3 cases. (4) Twenty-four patients in whom the livers revealed focal spared areas, which was misdiagnosed by sonographers in 14 cases, but correctly diagnosed by CT scan in all 24 cases.

We measured the haemodynamic changes following triglycyllysine vasopressin administration and after addition of nitroglycerin in twelve patients with portal hypertension due to hepatitis B-related cirrhosis. A bolus i.v. injection of triglycyllysine vasopressin at a dose of 2 mg reduced the hepatic venous pressure gradient from 18.5 +/- 3.7 (mean +/- S.D.) to 15.6 +/- 4.0 mmHg, p less than 0.001. However, the cardiac index decreased from 4.8 +/- 1.0 to 3.7 +/- 0.8 l/min m2, p less than 0.001; the heart rate decreased from 79 +/- 15 to 71 +/- 13, p less than 0.01; the right atrial pressure increased from 3.2 +/- 1.9 to 5.3 +/- 2.3 mmHg, p less than 0.001; the mean arterial pressure increased from 92 +/- 13 to 103 +/- 13 mmHg, p less than 0.05; and the systemic vascular resistance rose from 939 +/- 182 to 1367 +/- 310 dyn/s cm-5, p less than 0.001. Furthermore, both mean pulmonary arterial pressure and pulmonary capillary wedge pressure showed a significant increase following triglycyllysine vasopressin administration as compared with baseline values (p less than 0.005). The addition of sublingual nitroglycerin at a dose of 0.6 mg returned all the systemic haemodynamic parameters to baseline levels. On the other hand, nitroglycerin administration caused no further change in the hepatic venous pressure gradient. We concluded that although triglycyllysine vasopressin significantly reduced portal pressure in patients with hepatitis B-related cirrhosis, it produced untoward systemic haemodynamic changes similar to those seen with vasopressin. The addition of nitroglycerin improved the detrimental systemic haemodynamic effects produced by triglycyllysine vasopressin without further reducing the hepatic venous pressure gradient.

The spectrum of acute pancreatitis ranges from mild edematous disease to a severe necrotizing process which is usually accompanied by local or systemic complications and even mortality. Early deaths (within the first week) due to severe acute pancreatitis are generally caused by massive inflammatory responses which result in multiple organ failure. Although the exact mechanisms which trigger the inflammatory and necrotizing processes are not completely understood, it is generally accepted that autodigestion and activated leukocytes play important roles in the pathogenesis of acute pancreatitis. Proinflammatory cytokines are associated with systemic inflammatory response syndrome and multiple organ failure syndrome in acute pancreatitis. A compensatory anti-inflammatory response occurs in parallel with systemic inflammatory response syndrome. Trypsin secreted by the pancreatic acinar cells activates protease-activated receptor-2 which can result in the production of cytokines. Protease inhibitors such as aprotinin, gabexate mesilate, nafamostat mesilate, ulinastatin, etc. can inhibit the various enzymes and inflammatory response in experimental and clinical studies. Thus, protease inhibitors have been considered as a potential treatment to inhibit the pancreatic inflammation in acute pancreatitis. The beneficial effects of antiproteases on experimental severe acute pancreatitis may be, in part, due to the modulation of inflammatory cytokine responses. The effect of protease inhibitors on the inflammatory response in human acute pancreatitis deserves further study.

Splanchnic angiogenesis in liver cirrhosis often leads to complications as gastroesophageal variceal hemorrhage and the treatment efficacy is adversely affected by poor portal-systemic collateral vasoresponsiveness related to nitric oxide (NO). Purinergic receptor subtype P2X7 participates in the modulation of inflammation, angiogenesis, fibrogenesis and vasoresponsiveness, but the relevant influence in cirrhosis is unknown. Common bile duct-ligated (CBDL) or sham-operated Spraque-Dawley rats received brilliant blue G (BBG, a P2X7 antagonist and food additive) or vehicle from the 15th to 28th day after operations, then hemodynamics, mesenteric angiogenesis, portal-systemic shunting, liver fibrosis, and protein expressions of angiogenic and fibrogenic factors were evaluated. The influence of oxidized ATP (oATP, another P2X7 receptor antagonist) on the collateral vasoresponsiveness to arginine vasopressin (AVP) was also surveyed. BBG decreased superior mesenteric artery (SMA) flow, portal-systemic shunting, mesenteric vascular density, and mesenteric protein expressions of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), phospho (p)-VEGFR2, platelet-derived growth factor (PDGF), PDGF receptor beta (PDGFRβ), cyclooxygenase (COX)-1, COX-2, and endothelial NO synthase (eNOS) in CBDL rats. BBG also ameliorated liver fibrosis and down-regulated hepatic interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), PDGF, IL-1β, transforming growth factor-beta (TGF-β), p-extracellular-signal-regulated kinases (ERK), and alpha-smooth muscle actin (α-SMA) expressions in CBDL rats. The collateral vasocontractility to AVP was enhanced by oATP. oATP down-regulated eNOS, inducible NOS (iNOS), VEGF, Akt, p-Akt, and nuclear factor-kappa B (NF-κB) expressions in splenorenal shunt, the most prominent intra-abdominal collateral vessel in rodents. P2X7 antagonism alleviates splanchnic hyperemia, severity of portal-systemic shunting, mesenteric angiogenesis, liver fibrosis, and enhances portal-systemic collateral vasoresponsiveness in cirrhotic rats. P2X7 blockade may be a feasible strategy to control cirrhosis and complications.

Background: The pathogenetic mechanisms of hepatic encephalopathy (HE) are not fully understood. Cerebral blood flow regulated by cyclooxygenase (COX) may be involved in the development of HE. There are no comprehensive data concerning the effects of COX inhibition on HE in chronic liver disease. Methods: Male Sprague–Dawley rats weighing 240–270 g at the time of surgery were selected for experiments. Secondary biliary cirrhosis was induced by bile duct ligation (BDL). Those rats were then divided into two groups to receive i.p. injection of indomethacin (5 mg/kg per day) or distilled water for 7 days from day 36 to day 42 after BDL. The control group consisted of rats receiving a sham operation. Severity of encephalopathy was assessed by counts of motor activity. Plasma levels of tumor necrosis factor (TNF)-α and 6-keto-prostaglandin F1α (6-keto-PGF1α), and liver biochemistry tests were determined after treatment. Results: The motor activity in both groups of BDL rats were significantly lower than that of the control group (P < 0.001). As compared with the BDL rats treated with distilled water, BDL rats treated with indomethacin had significant lower levels of 6-keto-PGF1α, but the motor activity, TNF-α levels and serum biochemistry tests were not significantly different between both BDL groups. Conclusions: Chronic indomethacin administration did not have significantly detrimental or therapeutic effects on the severity of encephalopathy in BDL rats.

Background: Hepatic encephalopathy is a complex neuropsychiatric syndrome. A previous study showed that chronic nitric oxide (NO) inhibition aggravated the severity of encephalopathy in thioacetamide (TAA)-treated rats. The present study investigated the relative contribution of NO synthase (NOS) isoforms on the severity of hepatic encephalopathy in TAA-treated rats. Method: Fulminant hepatic failure was induced in male Sprague-Dawley rats by intraperitoneal injection of TAA (350 mg/kg/day) for 3 days. Rats were divided into three groups to receive Nω-nitro-L-arginine methyl ester (L-NAME, a non-selective NOS inhibitor, 25 mg/kg/day in tap water), L-canavanine (an inducible NOS inhibitor, 100 mg/kg/day via intraperitoneal injection) or normal saline (N/S) from 2 days prior to TAA administration and lasting for 5 days. Severity of encephalopathy was assessed by the counts of motor activity. Plasma levels of tumor necrosis factor-α (TNF- α) were determined by enzyme-linked immunosorbent assay (ELISA), and total bilirubin, alanine aminotransferase (ALT) and creatinine were determined by colorimetric assay. Results: Compared with L-canavanine or N/S-treated rats (0% and 4%, respectively), the mortality rate was significantly higher in rats receiving L-NAME administration (29%, P

Gabexate mesilate is a synthetic protease inhibitor. The effectiveness of gabexate mesilate in patients with acute pancreatitis is controversial. Proinflammatory cytokines are associated with systemic inflammatory response syndrome (SIRS) in acute pancreatitis. A compensatory anti-inflammatory response occurs in parallel with SIRS. We investigated the effects of gabexate mesilate on acute necrotizing pancreatitis in rats, emphasizing the changes in serum levels of proinflammatory and anti-inflammatory cytokines. Acute necrotizing pancreatitis was induced by retrograde infusion of sodium taurodeoxycholate into the pancreatobiliary duct in rats. The rats were divided into three groups. Group I was given gabexate mesilate 2 mg/kg/h i.v. continuously 1 h before the induction of acute pancreatitis. Group II was given gabexate mesilate the same dose immediately after the induction of acute pancreatitis. Group III was given normal saline as the controls. Serum levels of amylase, lipase, tumor necrosis factor alpha, interleukin-6, and interleukin-10, pancreatic histopathology and hemodynamics were examined at 5h after the induction of acute pancreatitis. Gabexate mesilate significantly reduced serum levels of amylase, lipase, tumor necrosis factor alpha and interleukin-6 at 5 h. Serum levels of interleukin-10 significantly increased in Group I, as compared with Groups II and III. The severity of pancreatic histopathology, the reduction of mean arterial pressure, the volume of ascites and pancreatic wet weight/body weight ratios were also significantly improved by the administration of gabexate mesilate. The beneficial effects of gabexate mesilate on acute pancreatitis may be, in part, due to the modulation of inflammatory cytokine responses.

Until now, the epidemiology of functional dyspepsia (FD) and its social impact on Asians have been rarely studied. The aims of this study were to determine the prevalence, social impact, and health-seeking behaviors of FD in an apparently healthy Chinese population in Taiwan.Based on the questionnaire provided by the Rome II working team, a survey was administered to a Taiwanese population receiving paid physical check-up (n = 2865). Esophagoduodenoscopy was performed in each subject to exclude organic dyspepsia. Finally, diagnoses of functional gastrointestinal disorders were obtained by means of a computer-generated algorithm.The FD prevalences were 23.8% and 11.8% according to the Rome I and -II criteria, respectively. Nearly 60% of Rome I-defined FD subjects and 18.9% of Rome II-defined FD subjects had overlapping irritable bowel syndrome (IBS). Irrespective of any Rome definition, FD subjects had excessive physician visits, absenteeism, and sleep disturbances compared to dyspepsia-free controls (p0.01). Moreover, over half of the Rome II FD subjects were "consulters" showing excessive physician visits, absenteeism, and sleep disturbances than "non-consulters". The dysmotility-like subgroup (74.5%) comprised the majority of FD subjects and showed no differences to their ulcer-like counterparts in terms of major demographic data and social and health impacts.FD is a common complaint in Taiwan and also bears an obvious social and medical burden to society. Over half of our FD subjects sought medical help, which may be due to the readily accessible medical care in Taiwan. The newly defined Rome II criteria diminish the chance of co-existence of FD and IBS. Further FD classification by the main symptoms appears of limited clinical usefulness.

Background: Recent studies have shown that endothelial nitric oxide (NO) is involved in modulating the vascular response to vasoconstrictors in portal-systemic collaterals of portal hypertensive rats. This study investigated which isoform of NO synthase is involved in the collateral circulation of portal hypertensive rats. Methods: The relaxation response to acetylcholine (10 -8 M, 10 -7 M and 10 -6 M) in norepinephrine (NE)-preconstricted portal-systemic collaterals was investigated after incubation with vehicle (Krebs solution), a preferential inducible NO synthase inhibitor (aminoguanidine (AG)), or a non-selective NO synthase inhibitor (N ω -nitro-L-arginine (NNA)), in rats with partial portal vein ligation. Mean arterial pressure was measured before the perfusion experiments. Results: Bodyweight and mean arterial pressure before the perfusion studies were similar in the vehicle, AG and NNA groups. Preincubation with NNA, but not AG, produced a significant increase in baseline perfusion pressure compared with the vehicle group (p < 0.05). The increase in perfusion pressure in response to NE was enhanced in the presence of NNA (p < 0.05), but not AG. In addition, preincubation with NNA, but not AG, significantly suppressed acetylcholine-induced relaxation in the portal-systemic collaterals (p < 0.05). Conclusion: These results suggest that constitutive, rather than inducible, NO synthase is involved in the vascular response to vasoconstrictors in the portal-systemic collaterals of portal hypertensive rats. (J Chin Med Assoc 2005; 68(6):245-249)

Arginine vasopressin (AVP) exerts a constrictive effect on the portal-systemic collaterals of non-cirrhotic portal hypertensive rats, but its effect on cirrhotic rats is unknown. The aim of this study was to investigate the response of AVP and the modulatory roles of nitric oxide and prostaglandin on collaterals of common bile duct-ligated (BDL) cirrhotic rats.The collateral vascular responsiveness to graded concentrations of AVP (10(-10) - 3 x 10(-7) M) was tested by an in situ collateral perfusion system pretreated with Nomega-nitro-L-arginine (L-NNA, 100 microM), indomethacin (INDO, 10 microM), or both. The collateral responses to AVP with the pretreatment of a vasopressin V1 receptor antagonist d(CH2)5Tyr(Me) arginine vasopressin or a V2 receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP, 10(-10) - 3 x 10(-7) M) were also evaluated.The perfusion pressure of collaterals was significantly increased by AVP, and this effect was inhibited by the addition of the V1 receptor antagonist. DDAVP had no effect on the collaterals. Incubation with L-NNA or L-NNA plus INDO, but not INDO alone, significantly potentiated the constrictive effects of AVP. The constrictive effect of AVP in the combination group was similar to that in the L-NNA alone group.The results show that AVP produces a direct vasoconstrictive effect on the portal-systemic collaterals of BDL cirrhotic rats. The constrictive effect of AVP is mediated by the vasopressin V1, instead of V2, receptors. Nitric oxide may play a more important role than prostaglandin in modulating the collateral vascular response to AVP in BDL cirrhotic rats.

Early diagnosis of acute pancreatitis remains a challenge. A rapid dipstick screening test for acute pancreatitis has been developed. This prospective study was designed to evaluate the diagnostic value and time course of the rapid urinary trypsinogen-2 test strip in acute pancreatitis, with comparisons with serum amylase and serum lipase.A total of 165 patients with acute abdominal pain (67 with acute pancreatitis and 98 with other acute abdominal diseases) attending our emergency unit were included. All patients were tested with the urinary trypsinogen-2 test strip, and serum amylase and serum lipase concentrations were determined simultaneously. To measure the time course of the urinary trypsinogen-2 test, 32 patients with acute pancreatitis were tested with a urinary trypsinogen-2 test strip on days 1, 2, 3, and 4 after admission.Using a cutoff level of 50 microg/L for urinary trypsinogen-2, the sensitivity, specificity, and accuracy of the urinary trypsinogen-2 test strip for recognition of acute pancreatitis were 89.6%, 85.7%, and 87.3%, respectively. The diagnostic accuracy rates of serum amylase and serum lipase were 88.5% and 93.3%, using cutoff values of 3 times the upper normal limits for serum amylase and serum lipase, respectively. All but one of the 17 patients with severe acute pancreatitis was detected by the test strip (sensitivity, 94.1%). The time-course study of the urinary trypsinogen-2 test strip revealed that the sensitivity on days 1, 2, 3, and 4 was 90.6%, 81.2%, 59.4%, and 50%, respectively. There was no significant difference in the sensitivity between urinary trypsinogen-2 and serum lipase; however, the sensitivity values of serum lipase were significantly higher than those of serum amylase from days 1 to 4.The rapid urinary trypsinogen-2 test is a reliable and simple method for the early diagnosis of acute pancreatitis. A positive test identifies patients in need of further diagnostic measures. The urinary trypsinogen-2 test can be performed in health care units where laboratory testing facilities are not immediately available.

Nitric oxide (NO) has been proposed to participate in the vascular hyporesponsiveness to vasopressin and its long-acting analogue glypressin during hemorrhage in portal hypertensive states. This study surveyed the role of NO regarding splanchnic hyporeactivity to glypressin and NO synthases (NOS) expression in different vascular beds in bleeding portal-hypertensive rats.Under general anesthesia with ketamine, partially portal vein-ligated male Sprague-Dawley rats without or with bleeding were used to investigate the hemodynamic effects of glypressin (0.07 mg/kg intravenously) and constitutive (cNOS) and inducible NOS (iNOS) mRNA expression over the abdominal aorta and superior mesenteric artery.Splanchnic hyposensitivity to glypressin was noted in the hemorrhage-transfused rats with enhanced cNOS expression of superior mesenteric artery. No significant differences of cNOS and iNOS expression in abdominal aorta and iNOS in superior mesenteric artery were found between the with-bleeding and without-bleeding groups.In rats with portal hypertension and acute hemorrhage, cNOS over-expression in superior mesenteric artery may take a part in the splanchnic hyposensitivity to glypressin.

The serum levels of proinflammatory cytokines have been reported to be significantly higher in severe acute pancreatitis compared with mild pancreatitis. Nitric oxide (NO) produced by cytokine-inducible NO synthase might be involved as the mechanisms for the progression of pancreatitis and the occurrence of systemic complications. The aim of the study was to evaluate the effects of a non-selective NO synthase inhibitor, nitro-L-arginine methyl ester (L-NAME), and an inducible NO synthase inhibitor, L-canavanine, on sodium taurodeoxycholate-induced acute necrotizing pancreatitis in rats.Twenty-eight rats were randomized into 3 groups to receive L-NAME 5 mg/kg/h, L-canavanine 20 mg/kg/h, and equivalent volume of saline, respectively, i.v. infusion after the induction of pancreatitis for 5 hours. The serum levels of amylase and lipase and mean arterial pressure and heart rate at baseline and 5 hours, and cardiac output, systemic vascular resistance, the amount of ascites and pancreatic histopathology at 5 hours were examined.Five hours after induction of pancreatitis, all rats treated with L-canavanine and all but 1 treated with saline survived; however, all rats treated with L-NAME died. As compared with the control group, L-canavanine significantly reduced serum levels of amylase and lipase, the severity of pancreatic edema and necrosis, and the volume of ascites in 5 hours. In addition, L-canavanine significantly improved the reduction of mean arterial pressure and systemic vascular resistance at 5 hours.L-NAME results in the mortality of acute necrotizing pancreatitis. L-canavanine reduces serum pancreatic enzymes and improves the changes of pancreatic histopathology and systemic hemodynamics at the early stage of acute pancreatitis. Inducible NO synthase inhibitor is beneficial for severe acute pancreatitis.

Nitric oxide (NO), a potent vasodilator, plays a significant role in the vascular hyposensitivity to vasoconstrictors related to portal hypertension. Chronic NO inhibition ameliorates portal-systemic collaterals in portal hypertensive rats. This study investigated whether chronic NO inhibition by NG-nitro-L-arginine methyl ester (L-NAME) improves the portal-systemic collateral vascular responsiveness to arginine vasopressin (AVP) in portal hypertensive rats.Partially portal vein-ligated (PVL) rats received L-NAME in tap water (approximately 25 mg/kg per day) or tap water only (control) since 2 days prior to until 7 days after PVL. Mean arterial pressure was measured on the 8th day. By in situ perfusion model, different concentrations of AVP (10(-10)-10(-7) M) with a constant flow rate (20 ml/min) were applied to assess the perfusion pressure of collateral vessels. In another series, perfusion with different flow rates (5-30 ml/min) was used to obtain flow-pressure curves: the slopes represent collateral vascular resistances and higher resistances indicate less collaterals.Mean arterial pressure was higher in the L-NAME-treated group than that of the control group (P0.05). As compared with the controls, L-NAME-treated rats achieved significantly higher perfusion pressures in response to AVP. In addition, chronic L-NAME treatment also induced an increase of collateral vascular resistance, suggesting the attenuation of portal-systemic shunting.Chronic NO inhibition ameliorates portal-systemic shunting and improves the collateral vascular responsiveness to AVP in portal hypertensive rats.

Hearing loss is a prevalent chronic problem among adults of all ages. Early identification and intervention for hearing loss will reduce the magnitude of functional disability. Hearing screening is an important item of physical examination. The purpose of this study is to evaluate the validity of hearing screening by means of the portable screening pure-tone audiometer and distortion-product otoacoustic emissions (DPOAE) measurement.This prospective study recruited 64 subjects visiting Taipei Veterans Hospital for physical examination. They underwent hearing tests performed with screening pure-tone audiometer, DPOAE and conventional pure-tone audiometer. The results of conventional pure-tone audiometry were used for "gold standards" and the normal auditory function was defined as the threshold less than or equal to 20 dB. Compared with the "gold standards," we used kappa statistic to assess the agreement of hearing results measured with screening pure-tone audiometer and DPOAE.For screening pure-tone audiometry, the kappa values at the 5 tested frequencies (0.5, 1, 2, 4, 8 kHz) ranged from 0.79 to 0.93 and the agreement with the gold standards was classified as "excellent." The sensitivity, specificity and test accuracy values ranged from 91.8-98.5%, 88.0-96.3% and 89.8-96.9%, respectively. For DPOAE measurement, the kappa values at the 3 tested frequencies (1, 2, 4 kHz) ranged from 0.62 to 0.78. The agreement was classified as "good" at 1, 4 kHz and "excellent" at 2 kHz. The sensitivity, specificity and test accuracy values ranged from 91.7-98.5%, 62.3-86.8% and 81.3-89.1%.We recommend a hearing screening measured at 0.5, 1, 2, 4, 8 kHz with screening pure-tone audiometer in a simple-type soundproof chamber and performed by a screening assistant. The DPOAE measurement may be used as an auxiliary tool to provide more information for early identification and differential diagnosis of hearing loss in clinical application.

Chronic gastroesophageal reflux disease is closely associated with esophageal adenocarcinoma and gastric cardia carcinoma, and esophageal adenocarcinoma and gastric cardia carcinoma have both been increasing in Western countries recently. Gastroesophageal reflux disease is not rare in Taiwan, but the frequency of occurrence of esophageal adenocarcinoma or gastric cardia carcinoma has not been studied here to date. Patients diagnosed with esophageal and gastric cancers at this hospital between 1981 and 1995 were recruited using the hospital tumor registry database. There were 45, 1546, 970, and 4167 patients diagnosed with esophageal adenocarcinoma, esophageal squamous cell carcinoma, gastric cardia carcinoma, and gastric noncardia adenocarcinoma, respectively. The ratios of esophageal adenocarcinoma versus esophageal squamous cell carcinoma among the three cohorts were 0.030, 0.016, and 0.041, respectively (trend, P = 0.086). The corresponding values for gastric cardia carcinoma versus gastric noncardia adenocarcinoma were 0.252, 0.232, and 0.218, respectively (trend, P = 0.256). The ratios of esophageal adenocarcinoma versus esophageal squamous cell carcinoma and of gastric cardia carcinoma versus gastric noncardia adenocarcinoma have not risen in the three cohorts. Unlike the situation in Western countries, the incidence of esophageal adenocarcinoma and gastric cardia carcinoma versus esophageal squamous cell carcinoma and gastric noncardia adenocarcinoma have not increased over the past 15 years among the Chinese in Taiwan. Although gastroesophageal reflux disease is common here, its definite pathogenesis leading to esophageal adenocarcinoma or gastric cardia carcinoma remains unresolved.

Hyperdynamic circulation observed in portal hypertension is characterized by generalized vasodilatation, increased cardiac index, and increased systemic and regional blood flows, and mediated at least partly by increased nitric oxide activities. Recent studies have demonstrated that Helicobacter pylori (H. pylori) infection can stimulate nitric oxide synthase expression and activities. This study investigated if chronic H. pylori infection might be involved in the development of hyperdynamic circulation in cirrhotic patients.Fifty-eight patients with cirrhosis and thirty-six healthy subjects entered this study. The serologic evidence of H. pylori infection was determined with ELISA in both groups. In addition, in cirrhotic patients hemodynamic studies were performed by Swan-Ganz catheterization and thermodilution technique.No significant differences in age (65.5 +/- 0.8 vs. 63.7 +/- 1.1 years), sex (male/female: 43/15 vs. 29/7) and seroprevalence of H. pylori (74.1% vs. 80.6%) were observed between cirrhotic patients and healthy subjects (P0.05). The seropositive rate of H. pylori in patients with cirrhosis was not associated with severity of cirrhosis and size of esophageal varices (P0.05). There were no significant differences in systemic vascular resistance and hepatic venous pressure gradient between cirrhotic patients with and those without chronic H. pylori infection (P0.05).The seroprevalence of H. pylori in cirrhotic patients is similar to that of healthy controls, and not related to the severity of cirrhosis and degree of portal hypertension. Chronic H. pylori infection does not play a major role in the hyperdynamic circulation observed in cirrhotic patients.

Nitric oxide (NO) participates in shock and poorer portal hypotensive effect to vasoconstrictors in portal hypertension with hemorrhage, the so-called splanchnic hyposensitivity. Relative adrenal insufficiency accompanies hemorrhagic shock and is found in liver disease, the 'hepatoadrenal syndrome', but the relevant interactions remain unsettled. Portal hypertensive rats were induced by partial portal vein ligation (PVL). Experiments were performed on the 14th day post PVL: (I) ACTH stimulation test for rats without or with hemorrhage; (II) Glypressin response (mean arterial pressure, MAP; portal pressure, PP) in rats (a) without hemorrhage or with hemorrhage, injected with (b) distilled water (DW), (c) dexamethasone 3 mg/kg; (III) To survey the dose-dependent effects of glucocorticoid without being confounded by endogenous adrenal hormone, glypressin response was surveyed in PVL rats with adrenalectomy: (a) without hemorrhage or with hemorrhage, injected with (b) DW; (c) dexamethasone 3 mg/kg; (d) dexamethasone 5 mg/kg. Plasma tumor necrosis factor-α (TNF-α) concentrations and abdominal aorta (AA), superior mesenteric artery (SMA) NO synthases (NOS) mRNA expressions were determined. The results showed that ACTH induced corticosterone release similarly in PVL rats with or without hemorrhage. In bleeding PVL rats, dexamethasone (1) down-regulated AA NOS and enhanced glypressin-induced MAP elevation; (2) did not influence glypressin-induced PP reduction; (3) reduced TNF-α. In bleeding PVL and adrenalectomized rats, high-dose dexamethasone (1) down-regulated AA/SMA NOS; (2) enhanced glypressin-induced MAP elevation and PP reduction; (3) reduced TNF-α. In conclusion, bleeding portal hypertensive rats failed to enhance corticosterone release, suggesting a relative adrenal insufficiency. High-dose dexamethasone reversed systemic hypotension and splanchnic hyporesponsiveness to glypressin in adrenalectomized PVL rats accompanied by TNF-α and NOS down-regulation, suggesting the importance of adequate adrenocorticoid supplement in portal hypertension with hemorrhage and adrenal dysfunction.

Portal hypertension is associated with increased hepatic and collateral resistance to an increased portal blood flow. Endothelin-1 (ET-1) can induce intrahepatic vasoconstriction and consequently increase portal pressure. It is unknown if ET-1 also modulates portal pressure by a direct vasoconstrictive effect on collaterals. This study investigated the collateral vascular responses to ET-1, the receptors in mediation, and the regulation of ET-1 action by nitric oxide and prostaglandin. The portal-systemic collaterals of partially portal vein-ligated rats were tested by in situ perfusion. The concentration-response curves of collaterals to graded concentrations of ET-1 (10(-10)-10(-7) mol/L) with or without BQ-123 (ET(A) receptor antagonist, 2 x 10(-6) mol/L), BQ-788 (ET(B) receptor antagonist, 10(-7) mol/L) or both were recorded. In addition, the collateral responses to ET-1 with preincubation of n(omega)-nitro-L-arginine (NNA; 100 mol/L), indomethacin (INDO; 10 mol/L), or in combination were performed. ET-1 increased the perfusion pressure of collaterals and its effect was significantly suppressed by BQ-123 alone and BQ-123 plus BQ-788, but not BQ-788 alone (P

Vasopressin given during hemorrhage is less effective than when given during a stable state in experimental portal hypertension or patients with cirrhosis (the so-called hyposensitivity phenomenon). This study investigated whether chronic inhibition of nitric oxide (NO) synthesis by NG-nitro-L-arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor, could potentiate the portal-hypotensive effect of glypressin (a long-acting vasopressin analogue) in portal-hypertensive rats during acute bleeding status.Portal hypertension was induced by partial portal vein ligation (PVL). Rats were divided to receive either L-NAME (approximately 25 mg/kg/day in tap water) or placebo (tap water) treatment orally from 2 days prior to until 14 days after the operation. At the end of treatment, L-NAME-and placebo-treated PVL rats were subdivided into without-bleeding and with-bleeding groups to assess the effects of glypressin (0.07 mg/kg) on systemic and portal hemodynamics. In rats with a hypotensive hemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin.As compared with placebo-treated rats, chronic treatment with L-NAME in PVL rats significantly increased mean arterial pressure (P0.001) without modulating portal pressure (P0.05). In placebo-treated PVL rats, glypressin resulted in a less decrease in portal pressure in rats with bleeding than in those without bleeding (P0.05). For PVL rats with bleeding, the portal-hypotensive effect of glypressin was significantly potentiated after chronic L-NAME treatment (P0.05).Chronic inhibition of NO alleviates the splanchnic hyposensitivity to glypressin observed in bleeding PVL rats, suggesting the pathophysiological role of nitric oxide in mediating this splanchnic hyposensitivity.

Hyposensitivity to vasopressin is a well-documented phenomenon in animals with portal hypertension and patients with cirrhosis and hemorrhage. Similar findings exist with infusion of glypressin (a long-acting vasopressin analogue), and this phenomenon could be ameliorated by inhibition of nitric oxide (NO) synthase. Besides NO, excessive formation of prostacyclin (PGI2) has been shown to play an important role in the development of hyperdynamic circulation and the mediation of hyporeactivity to vasoconstrictors in portal-hypertensive states. This study was designed to investigate whether the blockade of PGI2 activity by indomethacin infusion could enhance the portal-hypotensive effect of glypressin in portal-hypertensive rats with bleeding.Portal hypertension was induced by partial portal vein ligation (PVL). Fourteen days after operation systemic and portal hemodynamics were measured in stable or bleeding PVL rats receiving intravenous glypressin (0.07 mg/kg) or indomethacin (5 mg/kg) followed by glypressin infusion. In rats with a hypotensive hemorrhage 4.5 ml of blood was withdrawn, and 50% of the withdrawn blood was reinfused before the administration of glypressin or indomethacin.Splanchnic hyposensitivity to glypressin was shown in hemorrhage-transfused PVL rats. Indomethacin infusion did not cause significant systemic and portal-hemodynamic changes in bleeding PVL rats (P0.05). The addition of indomethacin significantly enhanced the portal-hypotensive effects of glypressin and potentiated the increases in mean arterial pressure induced by glypressin infusion in bleeding PVL rats.The improvement of splanchnic hyposensitivity to glypressin in a hemorrhage-transfused rat model of portal hypertension by the administration of indomethacin suggests that PGI2 has in the development of this hyposensitivity.

It has been reported that the serum uric acid levels in patients with cirrhosis were decreased compared with healthy subjects. These studies suggested that the lower serum uric acid levels in cirrhotic patients were attributed mainly to an increased effective vascular volume, and consequently to an excessive renal clearance of uric acid. However, the previous observations are challenged by a recent hypothesis for the pathogenesis of hyperdynamic circulation and formation of ascites in cirrhosis. The current study was undertaken to reevaluate serum uric acid levels in patients with cirrhosis. Ninety-eight cirrhotic patients with normal renal functions were included in this study. All biochemical and hemodynamic data were utilized for analysis. The mean serum uric acid level (mean, 6.1+/-1.2 mg/dL; range, 2.7-9.1 mg/dL) was higher than that of the age- and sex-matched healthy control subjects (mean, 5.5+/-1.3 mg/dL; range, 2.9-8.1 mg/dL; p = 0.018). Using multiple regression analysis it was determined that the serum uric acid level was not related to the severity of liver disease, cardiac index, systemic vascular resistance, and hepatic venous pressure gradient but was related closely to age (r = 0.210, p = 0.026) and effective renal plasma flow (r = -0.677, p < 0.0001). Compared with cirrhotic patients without ascites, those with ascites had a significantly higher serum uric acid level (6.7+/-1.6 mg/dL vs. 5.6+/-1.7 mg/dL, p < 0.05) and lower effective renal plasma flow (396+/-125 mL/min vs. 445+/-149 mL/min, p < 0.05). In conclusion, for cirrhotic patients with normal serum creatinine levels, the current study shows that the mean serum uric acid level is higher than that of healthy control subjects. It is not related to the severity of liver failure and systemic and portal hemodynamics, but is related closely to renal functions, especially the renal plasma flow.

This study investigated the effect of vasopressin on portal-systemic collaterals in portal hypertensive rats and the influence of nitric oxide (NO) and prostaglandin on the responsiveness of collateral vessels to vasopressin. The vascular responsiveness to graded concentrations of vasopressin was tested with or without the incubation of n(omega)-nitro-L-arginine (NNA) (100 micromol/L) and/or indomethacin (10 micromol/L) in perfused collateral vascular beds of rats with portal hypertension induced by partial portal vein ligation. In addition, concentration-response curves to vasopressin with incubation of a vasopressin V(1) receptor antagonist d(CH(2))(5)Tyr(Me) arginine vasopressin and concentration-response curves to a V(2) receptor agonist 1-desamino-8-D-arginine vasopressin were performed. Vasopressin significantly increased the perfusion pressure of collaterals, and this effect was suppressed by the addition of the V(1) receptor antagonist. Perfusion with the V(2) receptor agonist had no effect on the collaterals. Incubation with NNA, indomethacin, or both significantly potentiated the response of collaterals to vasopressin. In addition, the pressor response to vasopressin in the combination group was significantly higher than that in the NNA-alone group. The results show that vasopressin produces a direct vasoconstrictive effect on the portal-systemic collaterals of portal hypertensive rats. This effect is mediated by the vasopressin V(1,) but not V(2), receptors. The attenuation of the response to vasopressin by NO and prostaglandin suggest a function role of both mediators in the regulation of the portal-systemic collateral circulation in portal hypertensive rats.

Excessive formation of nitric oxide may mediate the generalized vasorelaxation and hyporesponsiveness to vasoconstrictors observed in portal hypertensive states. Endotoxin, released from the bowel and detoxified by the liver, could stimulate inducible nitric oxide synthase directly or indirectly via the cytokine cascade. This study investigated the effect of chronic intraperitoneal injection of polymyxin B, a neutralizing antagonist of endotoxin, on the hemodynamics of partially portal vein-ligated (PVL) rats.Concomitantly with endotoxin (600 EU) and dactinomycin (80 microg), polymyxin B (0.1 mg) or normal saline (N/S) was administered via an intraperitoneal route to male Sprague-Dawley rats. Twenty-four hours later, mean arterial pressure was determined. In PVL rats polymyxin B (0.1 mg in 5 cc N/S) or N/S was given intraperitoneally twice daily from 2 days prior to operation until 5 days (short-term) or 14 days (long-term) after the operation. Long-term polymyxin B- or N/S-treated sham-operated rats were included as controls. Hemodynamic studies with a thermodilution technique were performed at the end of treatment. Blood samples were collected from another series of PVL rats with long-term treatment to determine plasma levels of endotoxin and tumor necrosis factor-alpha. Plasma levels of endotoxin and tumor necrosis factor-alpha were measured by Limulus assay and the ELISA method, respectively.With the dosage of 0.1 mg polymyxin B, hypotension in rats subjected to endotoxin and dactinomycin administration could be corrected (polymyxin B vs. placebo: 130.0+/-7.7 vs. 108.8+/-6.7 mm Hg, p0.05). However, long-term or short-term treatment with the same dosage of polymyxin B failed to ameliorate the hyperdynamic circulation of PVL rats. In addition, long-term treatment with polymyxin B did not change systemic and portal hemodynamics in sham-operated rats. Plasma levels of endotoxin and tumor necrosis factor-alpha were comparable in PVL rats treated with long-term polymyxin B or N/S (p0.05).Our findings do not support the role of endotoxin in the hyperdynamic circulation of PVL rats.

Objective: Proinflammatory cytokines are involved in the pathogenesis of acute pancreatitis. The value of serum levels of tumor necrosis factor-α, interleukin-1-β, interleukin-6, and interleukin-8 in predicting the outcome of acute pancreatitis was evaluated. Methods: In 50 patients with acute pancreatitis, the serum concentrations of tumor necrosis factor-α, interleukin-1-β, interleukin-6, interleukin-8, and C-reactive protein were determined on days 1, 2, 3, 4, and 7 after admission. Acute Physiology and Chronic Health Evaluation (APACHE II) scores were recorded on days 1, 2, and 3. Results: Serum concentrations of interleukin-1-β, interleukin-6, interleukin-8, and C-reactive protein on days 1–7 were significantly higher in patients with severe pancreatitis than in patients with mild pancreatitis. Patients with severe attacks had significantly elevated serum tumor necrosis factor-α concentrations on days 1–3 compared with those with mild attacks, but not on days 4 and 7. The median peak value of tumor necrosis factor-α, interleukin-1-β, interleukin-6, and interleukin-8 was reached on day 1, in contrast to the median peak of C-reactive protein, which was reached on day 2. Using cutoff levels of 12 pg/ml for tumor necrosis factor-α, 1 pg/ml for interleukin-1-β, 400 pg/ml for interleukin-6, 100 pg/ml for interleukin-8, 12 mg/dl for C-reactive protein, and 10 for the Acute Physiology and Chronic Health Evaluation (APACHE II) score, the accuracy rates for detecting severe pancreatitis were 72%, 82%, 88%, 74%, 80%, and 72%, respectively, on day 1 and 78%, 74%, 80%, 76%, 80%, and 78%, respectively, on day 2. Conclusion: Among the proinflammatory cytokines, interleukin-6 is the most useful parameter for early prediction of the prognosis of acute pancreatitis.

1. Portal hypertension and hyperdynamic circulation have been postulated to play a role in the pathogenesis of portal hypertensive gastropathy. Administration of octreotide to portal hypertensive rats has been shown to reduce portal pressure and ameliorate hyperdynamic circulation. 2. This study investigated the effects of chronic administration of octreotide on systemic and portal haemodynamics and the development of portal hypertensive gastropathy in carbon tetrachloride-induced cirrhotic rats. 3. After 12 weeks of carbon tetrachloride induction, cirrhotic rats were randomly assigned to receive either placebo (5% dextrose in water) or octreotide (65 μg/kg in 5% dextrose in water) subcutaneously twice daily for 10 days. Haemodynamic studies with a thermodilution technique and gastric morphometric analyses were performed at 10 days after treatment. 4. In cirrhotic rats, octreotide treatment induced a significant increase in systemic vascular resistance (2.7 ± 0.2 versus 3.4 ± 0.2 mmHg/ml · min−1 · 100 g−1, P < 0.05) and decrease in portal pressure (12.5 ± 1.2 versus 9.9 · 0.5 mmHg, P < 0.05) compared with placebo-treated rats. In addition, octreotide treatment significantly reduced the mean cross-sectional area of gastric mucosal vessels (2290 ± 145 versus 1810 ± 101 μm2, P < 0.05). 5. This study shows that chronic octreotide treatment ameliorates the development of portal hypertensive gastropathy in cirrhotic rats. The effect of octreotide on portal hypertensive gastropathy may, at least partly, be due to the alleviation of portal hypertension and hyperdynamic circulation.

The effects of somatostatin and octreotide (a long acting somatostatin analogue) in acute pancreatitis are inconclusive. This study examined the prophylactic and therapeutic effects of different doses of octreotide on retrograde sodium taurodeoxycholate-induced acute necrotizing pancreatitis in rats. The rats were divided into 4 groups receiving subcutaneous injection of saline, octreotide 10 microg/kg, 20 microg/kg at 0, 8 and 16 h and octreotide 20 microg/kg at 5, 13 and 21 h, separately. The serum levels of amylase and lipase, pancreatic histopathology, mortality and hemodynamics were examined. Octreotide significantly reduced serum levels of amylase and lipase at 12 h and the degree of pancreatic edema, necrosis and hemorrhage at 18-24 h as compared to the control group. Prophylactic octreotide 10 microg/kg significantly decreased the 24-h mortality from 100% to 44.4% (p < 0.05). The 24-h mortality further reduced to 12.5% and 10% with prophylactic and therapeutic octreotide 20 microg/kg, respectively. The decrease of mean arterial pressure at 12 h was significantly lower in octreotide groups than in the control group. We conclude that octreotide improves pancreatic histopathology and survival in acute necrotizing pancreatitis in rats.

1. Hyperdynamic circulation observed in portal hypertensive states is characterized by generalized vasodilatation, increased cardiac index and increased systemic and regional blood flows. Endotoxin, tumour necrosis factor-alpha (TNF-α) and nitric oxide (NO) have been reported to be involved in the pathogenesis of hyperdynamic circulation, but the interactions between endotoxin, TNF-α and NO in cirrhotic rats with ascites have never been specifically addressed. 2. This study was designed to determine systemic and portal haemodynamics and plasma levels of endotoxin, TNF-α and nitrate/nitrite in cirrhotic rats with ascites and investigate the relationships between these substances. 3. Plasma concentrations of endotoxin, TNF-α and nitrate/nitrite (an index of NO production) were determined in 25 cirrhotic rats with ascites and 17 control rats using the Limulus assay, ELISA and a colorimetric assay respectively. In addition, haemodynamic studies were performed in another ten cirrhotic rats with ascites and ten control rats. 4. Cirrhotic rats with ascites had hyperdynamic circulation accompanied by increased plasma levels of endotoxin, TNF-α and nitrate/nitrite, as compared with control rats. Significant correlation existed between plasma levels of endotoxin and nitrate/nitrite (r = 0.59, P < 0.0001) and between plasma levels of endotoxin and TNF-α (r = 0.63, P < 0.0001). No correlation was detected between plasma levels of TNF-α and nitrate/nitrite (r = 0.24, P > 0.05). 5. This study suggests that endotoxaemia developed in cirrhotic rats with ascites may stimulate NO formation directly or indirectly via cytokine cascade, and consequently participate in the development and/or maintenance of hyperdynamic circulation.

The association between prolonged bleeding time and hepatocellular carcinoma (HCC) has not been well studied. We investigated whether bleeding time is prolonged in cirrhotic patients with HCC and studied the role of clinical characteristics, tumour size, and laboratory data in predicting bleeding time prolongation. After excluding patients that presented with blood dyscrasia and uraemia, 58 cirrhotic patients with HCC, 106 cirrhotic patients without HCC, and 44 age-and sex-matched healthy subjects were included in the study. Bleeding time, imaging studies, clinical characteristics and biochemical data were obtained for every patient. Cirrhotic patients with and without HCC had longer bleeding times (554 +/- 32 s, respectively) compared with healthy controls (357 +/- 13 s, P0.05). Hepatocellular carcinoma patients with a large tumour burden (5 cm in diameter) had a significantly longer bleeding time than those patients without (663 +/- 105 vs 376 +/- 23 s, respectively, P0.05). After excluding patients with a platelet countor = 80 000/mm3, cirrhotic patients classified as Child-Pugh's grading A and with a large tumour burden had longer bleeding times(580 +/- 87 s) than patients with a small tumour burden (or = 5cm in diameter) and cirrhotic patients without HCC (371 +/- 22 and 416 +/- 29 s, respectively, P0.05). In cirrhotic patients with HCC, higher serum bilirubin levels, a Child-Pugh's grading C, and a tumour size5 cm in diameter were found to be significant predictors for prolonged bleeding time on univariate analysis. On multivariate analysis, both tumour size5 cm in diameter and a Child-Pugh's grading C (odd's ratio, 95% confidence interval and P value were measured as 38.5, 2.8-534.7,0.001, and 10.5, 0.9-117.6, 0.02, respectively) were the significant independent predictors. A significant correlation existed between tumour diameter and bleeding time (r = 0.44, P0.01). In conclusion, these results suggest that prolonged bleeding time may be categorized as a new clinical manifestation in patients with HCC. In addition to cirrhosis, HCC itself may also participate in the pathogenesis of bleeding time prolongation.

Despite many attempts to create esophageal varices in experimental animals, most of them have failed. This study investigated whether rats with partial portal vein ligation (PVL) and left adrenal vein ligation (LAL) develop hyperdynamic circulation and dilated esophageal submucosal veins as compared with sham-operated (Sham) plus LAL rats.Two series of experiments were performed to measure (a) systemic and portal hemodynamics and (b) the cross-sectional area of esophageal submucosal veins in Sham, PVL, Sham plus LAL, and PVL plus LAL rats. Hemodynamic studies with a thermodilution technique and esophageal morphometric analyses were performed 14 days after the operation.PVL rats with or without LAL had a significantly lower mean arterial pressure and systemic vascular resistance accompanied by a significantly cardiac index and portal pressure than Sham rats with or without LAL (P0.05). LAL did not induce changes in mean arterial pressure, cardiac index, systemic vascular resistance, hear rate, or portal pressure in either Sham or PVL rats (P0.05). The mean cross-sectional area of esophageal submucosal veins in PVL rats with LAL (7340 +/- 833 microns2) was significantly larger than that in Sham rats with LAL (4236 +/- 556 microns2; P0.05). There was no significant difference in the mean cross-sectional area of esophageal submucosal veins between PVL and Sham rats without LAL.PVL rats with LAL developed hyperdynamic circulation similar to PVL rats without LAL. In addition, PVL plus LAL rats had larger esophageal submucosal veins than Sham plus LAL rats. This study shows that the esophageal submucosal veins of the 14-day partially portal vein-ligated rats with LAL resemble the structural abnormalities observed in human esophageal varices, suggesting that this model could be useful to investigate this entity.

This is a report of a phase II study of megestrol acetate (160 mg/day, orally) in the treatment of hepatocellular carcinoma (HCC). Forty-six patients with advanced HCC were studied and tumour response, changes in appetite, bodyweight, a feeling of well-being, survival and toxicity were evaluated. Thirty-two patients were able to be evaluated for response; there were no complete responders or partial responders. Twelve patients (38%) had stable disease and seven of these patients had a minor response with a median size reduction in the tumour of 18%. Twenty patients (62%) had progressive disease. Five of 24 (21%) patients had a median reduction in alpha-fetoprotein levels of 59 ng/mL. The overall median survival was 4 months (range 1 week to 27 months). Twenty of 32 (62%) patients had an increased appetite and feeling of well-being. Fourteen of 22 (64%) patients had a median lean bodyweight gain of 5 kg (range 1-14 kg). Toxicities were minimal. Tests for glucocorticoid receptors were performed in 10 patients. Four of five patients who were positive for glucocorticoid receptors in the tumour had a stable disease and all five patients who were negative for glucocorticoid receptors had progressive disease. Megestrol acetate had no significant effect on the tumour in HCC patients. However, megestrol acetate is useful in the palliative management of HCC patients, with improvements in appetite, bodyweight and a feeling of well-being with minimal side effects. Some patients had stable disease, a minor reduction of tumour size and a prolonged survival after megestrol acetate treatment and this response may be related to the presence of glucocorticoid receptors in the HCC tumour.

Background/Aims: Ascites may cause or aggravate pulmonary dysfunction in patients with liver cirrhosis. Diuretics and paracentesis are the main therapies for ascites. The aim of the present study was to evaluate and compare the therapeutic effects of diuretics and large-volume paracentesis on lung function in 26 male patients with non-alcoholic cirrhosis and tense ascites. Methods: The patients were divided into two groups. Group A was composed of 13 subjects who were treated with diuretics including spironolactone (100–400 mg/day) and furosemide (80–320 mg/day). In group B, 13 subjects received large-volume paracentesis plus intravenous albumin (6–8 g/l ascites removed). Pulmonary function tests including spirometry, plethysmography, single-breath carbon-monoxide diffusing capacity (DLco) and arterial blood gases, were done 1 day before diuretic treatment and 1 day after termination of the study in group A patients, and 1 day before and after large-volume paracentesis in group B subjects. Results: Before treatment, the clinical and laboratory data were comparable between the two groups. After treatment, ventillatory function as evidenced by forced expiratory volume in 1 s, forced vital capacity, total lung capacity, functional residual capacity and expiratory reserve volume, and DLco increased significantly in both groups. Arterial PO 2 and PCO 2 increased significantly and AaPO 2 (alveolar-arterial PO 2 difference) decreased significantly in the subjects treated with diuretics. Nevertheless, paracentesis did not improve arterial blood gases. The changes in lung volumes, DLco and PaO 2 after treatment (the data after minus those before treatment) were comparable, except that a significant decrease in AaPO 2 was observed in the diuretic group. Conclusion: Both diuretic therapy and large-volume paracentesis significantly improved the ventilatory function in patients with tense cirrhotic ascites. In terms of oxygenation improvement as evaluated by AaPO 2 , diuretic treatment may be superior to large-volume paracentesis.