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Biomedical subjects

Y T Tsai

Publications and source records attributed to Y T Tsai.

At least 19 recordsLinked to original sources

Clinical value of early cleavage embryo.

OBJECTIVE: This study was undertaken to see if embryo transfer containing early cleavage embryos resulted in better clinical pregnancy rate. METHODS: The treatment outcomes of IVF-ET were retrospectively reviewed. Out of 258 transfer cycles, 160 cycles contained no early cleavage embryos (Group I) and 98 cycles contained at least one early cleavage embryo (Group II). The definition of early cleavage embryo is the presence of two blastomeres 24-26 h after insemination. The implantation rate, clinical pregnancy rate were compared between two groups. Student's t-test and the Mann-Whitney U-test were used for continuous variables, and the Chi-squared (chi(2)) test was used for binary variables. Differences were considered statistically significant at P<0.05. RESULT: The implantation rate and clinical pregnancy rate were 11.6% and 25.6% in Group I, 18.6% and 38.8% in Group II (P<0.05). CONCLUSION: Early cleavage embryos possess greater implantation potential. Embryo transfer containing early cleavage embryos had a better clinical pregnancy rate.

Adult↗

Arteriovenous fistula using transposed basilic vein in chronic hypotensive hemodialysis patients.

AIM: Chronic hypotension is not uncommon in uremic patients on regular hemodialysis. This subset of patients often requires multiple operations to maintain their vascular access due to frequent thrombosis and occlusion of the arteriovenous fistula. Our aims was to assess whether surgical intervention with the brachial artery-transposed basilic vein fistula is effective in chronic hypotensive hemodialysis patients. MATERIALS AND METHODS: Fifty-four hemodialysis patients with chronic hypotension were enrolled in this study. Most ofthem were referred from local hospitals. They were 23 men and 31 women. The brachial artery-transposed basilic vein arteriovenous fistula was performed in a period of 46 months at the teaching hospital. Primary patency was defined as the length of time from the fistula creation until the development of thrombosis or a complication that required operative revision ofthe fistula. Secondary patency was defined by whether the fistula could be salvaged by revision such that blood flow was maintained. RESULTS: There was no technical failure and none of these patients died due to the surgical operation. The primary patency rate was 89.80% at 1 year, 73.08% at 2 years, and 64.710% at 3 years. The secondary patency rate was 95.92% at 1 year, 84.62% at 2 years, and 76.47% at 3 years. CONCLUSIONS: Brachial artery-transposed basilic vein arteriovenous fistula may present good primary alternative vascular access in chronic hypotensive hemodialysis patients.

Adult↗

Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation.

Etk (also called Bmx) is a member of the Btk tyrosine kinase family and is expressed in a variety of hematopoietic, epithelial, and endothelial cells. We have explored biological functions, regulators, and effectors of Etk. Coexpression of v-Src and Etk led to a transphosphorylation on tyrosine 566 of Etk and subsequent autophosphorylation. These events correlated with a substantial increase in the kinase activity of Etk. STAT3, which was previously shown to be activated by Etk, associated with Etk in vivo. To investigate whether Etk could mediate v-Src-induced activation of STAT3 and cell transformation, we overexpressed a dominant-negative mutant of Etk in an immortalized, untransformed rat liver epithelial cell line, WB, which contains endogenous Etk. Dominant-negative inactivation of Etk not only blocked v-Src-induced tyrosine phosphorylation and activation of STAT3 but also caused a great reduction in the transforming activity of v-Src. In NIH3T3 cells, although Etk did not itself induce transformation, it effectively enhanced the transforming ability of a partially active c-Src mutant (c-Src378G). Furthermore, Etk activated STAT3-mediated gene expression in synergy with this Src mutant. Our findings thus indicate that Etk is a critical mediator of Src-induced cell transformation and STAT3 activation. The role of STAT3 in Etk-mediated transformation was also examined. Expression of Etk in a human hepatoma cell line Hep3B resulted in a significant increase in its transforming ability, and this effect was abrogated by dominant-negative inhibition of STAT3. These data strongly suggest that Etk links Src to STAT3 activation. Furthermore, Src-Etk-STAT3 is an important pathway in cellular transformation.

Animals↗

Simplified rat intubation using a new oropharyngeal intubation wedge.

Our new oropharyngeal intubation wedge made from a plastic 3-ml syringe has been used successfully for the expansion of the oropharyngeal cavity and visualization of vocal cords for endotracheal intubation in the rat. All the animals we used tolerated the intubation and ventilation procedures in a series of experiments. After the proper setting of the respirator, vital signs were maintained within normal range. The postmortem examination and measurements in the upper airway confirmed that the endotracheal tube was properly sited and also demonstrated the precise size of the device that should be used. The main advantages of this method include low cost, simplicity, and reliability. Furthermore, because no expensive, elaborate, difficult-to-operate, or hard-to-get special equipment is needed, this technique can be used in every laboratory.

Animals↗

Sequential changes in plasma cytokine and endotoxin levels in cirrhotic patients with bacterial infection.

To delineate the clinical roles of plasma cytokine or endotoxin levels in the natural course of infection in patients with decompensated cirrhosis, 66 cirrhotic patients were studied within a 1.5-year period. Plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8 and endotoxin were determined on days 1, 4 and 7 after admission when hospital infection was suspected and 4 months later. A total of 24 patients (36.4%) were proven to be infected during hospitalization (group A), while 42 others were not infected (group B). Fever occurred in a very high proportion (22/24) of group A patients. Baseline levels of TNF-alpha (37.7+/-15.2 compared with 8.7+/-1.2 pg/ml; P<0.01) and IL-6 (180.5+/-20.5 compared with 24.6+/-7.5 pg/ml; P<0.0001) were higher in group A patients, while IL-1beta, IL-8 and endotoxin levels were not significantly different between the two groups. For patients with hospital infection, IL-6 levels determined during the episode were significantly higher than baseline levels. Using IL-6 >80 pg/ml as a baseline cut-off level to diagnose bacterial infection, the sensitivity, specificity and accuracy were 87.5, 100 and 95.5% respectively. The one-year cumulative probability of mortality (61.1% compared with 23.7%; P<0.001) and of bacterial re-infection (72.2% compared with 18.4%; P<0.0001) was higher in group A than in group B. Plasma TNF-alpha and IL-6 levels determined at 4 months were not different between the two groups. In conclusion, fever or elevated plasma IL-6 levels in patients with decompensated cirrhosis calls for early antibiotic treatment to prevent life-threatening bacterial infection. Bacterial infection is likely to recur in those patients with increased IL-6 levels, while severe episodes of infection occur in patients with increased TNF-alpha levels.

Aged↗

Establishment of an animal model of hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy is a neuropsychiatric syndrome associated with acute liver failure, chronic parenchymal liver disease or portal systemic anastomosis. The spectrum of symptoms may vary from subtle mental changes to a disrupted circadian rhythm to hepatic coma. In order to investigate the possible pathogenetic mediators and the use of potential new therapies, the aim of our study was to create a reliable animal model for research on hepatic encephalopathy. METHODS: Forty male Sprague-Dawley rats were used. Fulminant hepatic failure was induced by intraperitoneal injection of thioacetamide (TAA, 350 mg/kg) for three consecutive days (n = 30). Rats treated with normal saline served as controls (n = 10). The clinical stage of hepatic encephalopathy in TAA-treated rats was graded according to neurobehavioral testing. Spontaneous motor activities of rats were calculated using the Opto-Varimex animal activity meter. We also investigated the relationships between the neurobehavioral score and the motor activity count. RESULTS: Compared with normal, saline-treated rats, those receiving consecutive injections of TAA had apparently lower neurobehavioral scores (p < 0.001) accompanied by significantly blunted motor activities (p < 0.001). A significant correlation was demonstrated between the neurobehavioral score and total movements in rats with encephalopathy (r = 0.71, p < 0.001). In addition, the neurobehavioral score also correlated well with ambulatory movements (r = 0.73, p < 0.001) and vertical movements (r = 0.45, p < 0.05). CONCLUSIONS: The rat model is acceptable for the study of hepatic encephalopathy, as established in this study. This experimental model can be used to explore the pathogenesis and management of hepatic encephalopathy.

Animals↗

Interleukin-6 inhibits transforming growth factor-beta-induced apoptosis through the phosphatidylinositol 3-kinase/Akt and signal transducers and activators of transcription 3 pathways.

The multifunctional cytokine interleukin-6 (IL-6) regulates growth and differentiation of many cell types and induces production of acute-phase proteins in hepatocytes. Here we report that IL-6 protects hepatoma cells from apoptosis induced by transforming growth factor-beta (TGF-beta), a well known apoptotic inducer in liver cells. Addition of IL-6 blocked TGF-beta-induced activation of caspase-3 while showing no effect on the induction of plasminogen activator inhibitor-1 and p15(INK4B) genes, indicating that IL-6 interferes with only a subset of TGF-beta activities. To further elucidate the mechanism of this anti-apoptotic effect of IL-6, we investigated which signaling pathway transduced by IL-6 is responsible for this effect. IL-6 stimulation of hepatoma cells induced a rapid tyrosine phosphorylation of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) and its kinase activity followed by the activation of Akt. Inhibition of PI 3-kinase by wortmannin or LY294002 abolished the protection of IL-6 against TGF-beta-induced apoptosis. A dominant-negative Akt also abrogated this anti-apoptotic effect. Dominant-negative inhibition of STAT3, however, only weakly attenuated the IL-6-induced protection. Finally, inhibition of both STAT3 and PI 3-kinase by treating cells overexpressing the dominant-negative STAT3 with LY294002 completely blocked IL-6-induced survival signal. Thus, concomitant activation of the PI 3-kinase/Akt and the STAT3 pathways mediates the anti-apoptotic effect of IL-6 against TGF-beta, with the former likely playing a major role in this anti-apoptosis.

Apoptosis↗

Effect of anaemia on haemodynamics in patients with cirrhosis.

BACKGROUND: It has been suggested that increased blood haemoglobin attenuates splanchnic vasodilatation in portal-hypertensive rats by nitric oxide inactivation. However, the haemodynamic effect of anaemia in cirrhotic patients of varying severity has been rarely discussed. The aim of this study was to evaluate the influence of anaemia on systemic and splanchnic haemodynamics in cirrhotic patients of differing severity. METHODS: Two hundred and twenty-five cirrhotic patients were included in this study. All biochemical and haemodynamic results were utilized for analysis. Anaemia was defined as a haemoglobin level below the cut-off value of 12 g/dL, which might best predict low systemic vascular resistance. RESULTS: Compared with non-anaemic patients, anaemic patients had decreased mean arterial pressure (90 +/- 1 vs 95 +/- 1 mmHg, P = 0.002), and decreased systemic vascular resistance (1022 +/- 25 vs 1227 +/- 30, P < 0.0001), and increased cardiac index (4.3 +/- 0.1 vs 3.8 +/- 0.1 L/min per m2, P < 0.0001) and increased hepatic venous pressure gradient (16.7 +/- 0.5 vs 14.4 +/- 0.6 mmHg, P = 0.006). Haemoglobin concentration exerted an influence on the degree of vasodilatation in cirrhotic patients, with Child-Pugh's A class (but not in Child-Pugh's B and C classes), and in patients without ascites (but not in patients with ascites). CONCLUSIONS: It was concluded that anaemia has a negative effect on hyperdynamic circulation in patients with early cirrhosis which is not observed in patients with advanced cirrhosis.

Anemia↗

Effects of octreotide on central hemodynamics and systemic oxygen use in patients with viral cirrhosis.

OBJECTIVE: Octreotide has potentially beneficial effects in patients with cirrhosis. However, the effects of octreotide on central hemodynamics and oxygen use have not been established. The present study was undertaken to evaluate the effect of octreotide on central hemodynamics and oxygen use in patients with viral cirrhosis. METHODS: Twenty-five patients with cirrhosis were enrolled in the study. They were randomly assigned to receive either placebo (n = 10) or a continuous infusion of 100 microg/h of octreotide after an initial 100-microg bolus (n = 15). Hemodynamic measurements and oxygenation values were obtained before and 60 min after octreotide or placebo administration. RESULTS: Placebo administration did not have any effect on hemodynamic and oxygenation values. In patients who received octreotide, systemic hemodynamic values including cardiac index, mean arterial pressure, and systemic vascular resistance were not affected. The mean pulmonary arterial pressure tended to increase after octreotide administration but was statistically insignificant. There was a significant increase in pulmonary arterial vascular resistance, whereas the pulmonary capillary wedge pressure and right atrial pressure were significantly decreased. Arterial oxygen tension, systemic oxygen uptake, and oxygen extraction ratio were significantly decreased after octreotide administration, whereas oxygen transport as well as arterial and mixed venous oxygen contents remained unchanged. CONCLUSIONS: In patients with viral cirrhosis, octreotide administration exerted a significant effect on pulmonary circulation. It also resulted in a decrease in systemic oxygen uptake and oxygen extraction ratio. These results suggested that octreotide may impair tissue oxygenation in patients with viral cirrhosis.

Aged↗

Planning of skull base surgery in the virtual workbench: clinical experiences.

Based on the KRDL Virtual Workbench, we present a neurosurgical planning system called VIVIAN (Virtual Intracranial Visualization And Navigation). This VR environment allows for fast and intuitive interaction with three-dimensional multimodal (MRI, MRA, MRV, CT) patient specific data-sets. The user reaches behind a mirror into a 3D workspace where the 3D data is surrounded by interactive virtual tools-racks. Tumors, blood vessels, cranial nerves and surgically relevant parts of the brain are segmented by interactive control of density transfer-functions or by manual outlining and tracing tools. A neurosurgical procedure is planned by using various visualization and measurement tools and the system allows for the simulation of bone drilling and tissue removal. We have planned 16 cases which required tumor surgery at the cranial base. VIVIAN provided an efficient and comprehensive way to understand pre-operatively the complexity of anatomical and pathological relationships. The ideal craniotomy and the extent of the required skull base exposure could be specified accurately.

Computer Simulation↗

Effect of long-term octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis.

1. Both octreotide and isosorbide dinitrate have been shown to have portal hypotensive effects in animals with portal hypertension. Moreover, in both animals and humans with portal hypertension, the reduction of portal pressure was enhanced when nitrovasodilators were combined with propranolol or vasopressin. The present study was undertaken to evaluate the effect of long-term administration of octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis. 2. Portal hypertension was induced by portal vein stenosis. Portal hypertensive rats were allocated into one of four groups (eight rats in each group): vehicle group, octreotide group (100 micrograms/kg via subcutaneous injection every 12 h), isosorbide dinitrate group (5 mg/kg via gastric gavage every 12 h) and combined treatment group. Drug was given for eight consecutive days, starting 1 day before surgery. Haemodynamic values were measured using a radioactive microsphere technique. 3. Long-term octreotide treatment decreased portal pressure and improved the hyperdynamic circulation. In contrast, long-term administration of isosorbide dinitrate reduced portal pressure but did not ameliorate vasodilatation. A combination of octreotide and isosorbide dinitrate improved the hyperdynamic circulation with a reduction of portal pressure. In addition, the mean value of portal pressure after combination treatment was significantly lower than in rats receiving octreotide alone. 4. These results showed that, in rats with portal hypertension, long-term combined administration of octreotide and isosorbide dinitrate improved the hyperdynamic circulation together with a more profound reduction of portal pressure than rats receiving octreotide alone.

Animals↗

Endoscopic variceal ligation in prophylaxis of first variceal bleeding in cirrhotic patients with high-risk esophageal varices.

To determine the efficacy of endoscopic variceal ligation (EVL) in prophylaxis on the rate of first esophageal variceal bleeding, we conducted a prospective, randomized trial in 126 cirrhotic patients with no history of previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage. The end-points of the study were bleeding and death. Life-table curves showed that prophylactic EVL significantly diminished the rate of variceal hemorrhage (12/62 [19%] vs. 38/64 [60%]; P = .0001) and overall mortality (17/62 [28%] vs. 37/64 [58%]; P = .0011). The 2-year cumulative bleeding rate was 19% (12/ 62) in the EVL group and 60% (38/64) in the control group. The 2-year cumulative mortality rate was 28% (17/62) in the EVL group and 58% (37/64) in the control group. Comparison of Kaplan-Meier estimates of the time to death of both groups showed significantly lower mortality in the ligation group (P = .001). Patients undergoing EVL had few treatment failures and died mainly of hepatic failure. The lower risk in the EVL group was attributed to a rapid reduction of variceal size. Prophylactic EVL was more efficient in preventing first bleeding in patients with good condition (Child A) than in those with decompensated disease (Child B and C). We conclude that prophylactic EVL can decrease the incidence of first variceal bleeding and death over a period of 2 years in cirrhotic patients with high-risk esophageal varices.

Aged↗

Effects of long-term administration of octreotide on sodium retention and atrial natriuretic peptide in carbon tetrachloride-induced cirrhotic rats.

BACKGROUND/AIMS: To realize the roles of peripheral vasodilatation and atrial natriuretic peptide in the formation of cirrhotic ascites, the effects of long-term administration of octreotide on carbon tetrachloride-induced cirrhotic rats were evaluated. METHODS: Urine sodium excretion, hemodynamics, plasma atrial natriuretic peptide levels, renin activities and aldosterone concentrations were compared between cirrhotic and control rats (protocol 1); and between octreotide- (65 micrograms/kg, twice daily for 10 days, subcutaneously) and placebo-treated (5% dextrose) cirrhotic rats (protocol 2). In an in vitro experiment, right atrial tissue of cirrhotic rats was incubated with different concentrations of octreotide to evaluate the release of atrial natriuretic peptide (protocol 3). RESULTS: Cirrhotic rats had significantly lower urine sodium excretion and systemic vascular resistance, and significantly higher plasma atrial natriuretic peptide levels, renin activities and aldosterone concentrations than control rats. Compared with placebo-treated cirrhotic rats, octreotide caused increased urine sodium excretion (-10 +/- 4% vs. 13 +/- 8% from baseline values, p < 0.05) and systemic vascular resistance (2.6 +/- 0.1 vs. 3.3 +/- 0.3 mmHg.min.100 g.ml-1, p < 0.05); and decreased plasma atrial natriuretic peptide levels (166.7 +/- 24.8 vs. 234.0 +/- 19.2 pg/ ml, p < 0.05), renin activities (2.45 +/- 0.49 vs. 4.36 +/- 0.53 ng.ml-1.h-1, p < 0.01) and aldosterone concentrations (290.2 +/- 40.0 vs. 483.3 +/- 82.6 pg/ml, p < 0.05). In the in vitro experiment, right atrial release of atrial natriuretic peptide of cirrhotic rats was not significantly changed when incubated with different concentrations of octreotide. CONCLUSIONS: Octreotide ameliorates renal sodium retention and suppresses plasma levels of atrial natriuretic peptide of ascitic cirrhotic rats with a novel mechanism via, at least partly, the modification of peripheral vascular resistance.

Animals↗

Aminoguanidine corrects hyperdynamic circulation without ameliorating portal hypertension and portal hypertensive gastropathy in anesthetized portal hypertensive rats.

BACKGROUND/AIMS: Portal hypertension and hyperdynamic circulation (i.e. generalized vasodilation and increased cardiac output and regional organ blood flows) may play an important role in the development of portal hypertensive gastropathy. This study investigated the effect of chronic administration of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, to portal hypertensive rats on hemodynamics and the development of portal hypertensive gastropathy. METHODS: Partial portal vein-ligated or sham-operated rats were randomly assigned to receive either placebo (distilled water) or aminoguanidine (approximately 100 mg/kg per day subcutaneously) for 2 days prior to and 14 days. Hemodynamic studies with a thermodilution technique and gastric morphometric analysis were performed at 14 days after the operation. RESULTS: In rats given placebo, portal vein-ligated rats had a significantly lower mean arterial pressure and systemic vascular resistance associated with a significantly higher cardiac index and portal pressure than sham-operated rats (p<0.05). In portal vein-ligated rats aminoguanidine induced a significant increase in mean arterial pressure and systemic vascular resistance accompanied by a significant decrease in cardiac index (p<0.05) without changes in portal pressure (p>0.05). Despite persistence of portal hypertension, the aminoguanidine-treated portal vein-ligated rats had similar mean arterial pressure, cardiac index, and systemic vascular resistance as seen in placebo-treated sham-operated rats. The mean cross-sectional area of gastric mucosal vessels was significantly higher in placebo-treated portal vein-ligated than in placebo-treated sham-operated rats (p<0.05). Treatment with aminoguanidine did not induce changes in the mean cross-sectional area of gastric mucosal vessels in either portal vein-ligated or sham-operated rats (p>0.05). CONCLUSIONS: The results show that in portal hypertensive rats long-term aminoguanidine therapy corrects the hyperdynamic circulation without inducing changes in portal pressure and ameliorating the development of portal hypertensive gastropathy. This study suggests that, instead of correcting hyperdynamic circulation, treatment of portal hypertensive gastropathy should be aimed at reducing portal pressure.

Animals↗

Hyperdynamic circulation of cirrhotic rats with ascites: role of endotoxin, tumour necrosis factor-alpha and nitric oxide.

1. Hyperdynamic circulation observed in portal hypertensive states is characterized by generalized vasodilation, increased cardiac index and increased systemic and regional blood flows. Endotoxin, tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) have been reported to be involved in the pathogenesis of hyperdynamic circulation, but the interactions between endotoxin, TNF-alpha 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-alpha and nitrate/nitrite in cirrhotic rats with ascites and investigate the relationships between these substances. 3. Plasma concentrations of endotoxin, TNF-alpha 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-alpha 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-alpha (r = 0.63, P < 0.0001). No correlation was detected between plasma levels of TNF-alpha 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.

Animals↗

Gall-bladder wall thickening in patients with liver cirrhosis.

Gall-bladder wall thickening is commonly seen in patients with cirrhosis, but its exact causes have not been well established. We evaluated clinical, biochemical and haemodynamic data of patients with cirrhosis with respect to the presence of thickening of the gall-bladder wall. After excluding patients who presented with gallstones, acute or chronic cholecystitis, heart failure, a serum creatinine level greater than 2 mg/dL and/or a serum alanine aminotransferase level greater than 400 U/L, 77 patients with cirrhosis (75 male, two female; mean age 58 +/- 8 years) were enrolled in the study. Clinical, biochemical, ultrasound and haemodynamic data were obtained in every patient. Forty-one (53%) of 77 patients with cirrhosis had gall-bladder wall thickening (> 4 mm). Compared with patients with a normal gall-bladder wall, patients with gall-bladder wall thickening had significantly lower serum albumin levels (3.6 +/- 0.6 vs 2.9 +/- 0.7 gm/dL, respectively; P < 0.05), a longer prothrombin time (13 +/- 6 vs 16 +/- 6 s, respectively; P < 0.05), more patients with Child-Pugh class C (6 vs 37%, respectively; P < 0.05) and more patients with ascites (8 vs 50%, respectively; P < 0.05). In addition, compared with patients with a normal gall-bladder wall, those patients with gall-bladder wall thickening had a higher hepatic venous pressure gradient (13.9 +/- 4.5 vs 17.1 +/- 4.1 mmHg, respectively; P < 0.01) and a lower systemic vascular resistance (SVR; 1144 +/- 332 vs 1010 +/- 318 dyn.s/cm5, respectively; P < 0.05). Using a multivariate analysis, the presence of ascites and SVR lower than 900 dyn.s/cm5 were independently correlated with the presence of gall-bladder wall thickening, while a hepatic vein pressure gradient greater than 10 mmHg had only a marginally significant association. The presence of ascites, decreased SVR and portal hypertension are related to the occurrence of gall-bladder wall thickening in patients with cirrhosis, indicating that the development of gall-bladder wall thickening may be multifactorial.

Ascites↗

Prolonged bleeding time: a new clinical manifestation of hepatocellular carcinoma?

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, P < 0.05). 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, P < 0.05). After excluding patients with a platelet count < or = 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, P < 0.05). In cirrhotic patients with HCC, higher serum bilirubin levels, a Child-Pugh's grading C, and a tumour size > 5 cm in diameter were found to be significant predictors for prolonged bleeding time on univariate analysis. On multivariate analysis, both tumour size > 5 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, P < 0.01). 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.

Bleeding Time↗