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The origin of large-scale ancient dolomite is one of the most hotly debated topics in sedimentology. The Loushanguan group of the upper 3rd-Furongian Cambrian series on the south-eastern margin of the Sichuan Basin consists of numerous dolomites, and the origins of these dolomites have never been reported previously although they are probably good hydrocarbon reservoirs. Based on a systematic analysis of petrology, fluid inclusions, carbon and oxygen isotopes, trace elements and rare earth elements ( REEs), this study provides some unique insights into the origins of the dolomites. Four dolomite types have been identified in the study area: dolomicrite, fabric-retentive oolitic dolomite, fabric-obliterative dolomite and saddle dolomite cement. In the dolomicrite and fabric-retentive oolitic dolomite, high Sr contents (with respect to the fabric-obliterative dolomite) and the lack of two-phase aqueous inclusions suggest that they formed at shallow-to-intermediate burial depths at low temperatures (<50-60°C). Carbon and oxygen isotopes and seawater-like REE+Y characteristics of the dolomicrite and fabric-retentive oolitic dolomite indicate that the dolomitizing fluids were evaporated seawater or slightly modified seawater. The obliteration of the original sedimentary fabric and relatively low δ18O and Sr values compared to the fabric-retentive dolomite indicate that fabric-obliterative dolomite formed at intermediate-to-deep burial diagenesis. The chemical composition approaches pure dolomite and the REE+Y characteristics are similar to those of the fabric-retentive dolomite, indicating that the fabric-obliterative dolomite was formed due to the recrystallization of the previously formed fabric-retentive dolomite at elevated burial depths and temperatures. High fluid inclusion homogenization temperatures (115-150°C), low δ18O values, nonplanar-a crystals and seawater-like REE+Y characteristics suggest that saddle dolomite cement formed by reprecipitation of dolomite that related to seawater-driven and deep burial fluid. In the study area, dolomicrite and fabric-retentive oolitic dolomite may have been formed by penecontemporaneous or seepage-reflux dolomitization during early-stage diagenesis. Subsequently, during progressive burial, most of the fabric-retentive dolomite was converted into fabric-obliterative dolomite by recrystallization. This study confirms that fabric-obliterative dolomite was the main dolomite type, and although deeply buried, these Cambrian dolomites most likely have preserved coeval seawater geochemical signals. [ABSTRACT FROM AUTHOR]

The declining number of physician scientists is an alarming issue. A systematic review of all existing programs described in the literature was performed, so as to highlight which programs may serve as the best models for the training of successful physician scientists. Multiple databases were searched, and 1,294 articles related to physician scientist training were identified. Preference was given to studies that looked at number of confirmed publications and/or research grants as primary outcomes. Thirteen programs were identified in nine studies. Eighty-three percent of Medical Scientist Training Program (MSTP) graduates, 77% of Clinician Investigator Training Program (CI) graduates, and only 16% of Medical Fellows Program graduates entered a career in academics. Seventy-eight percent of MSTP graduates succeeded in obtaining National Institute of Health (NIH) grants, while only 15% of Mayo Clinic National Research Service Award-T32 graduates obtained NIH grants. MSTP physician scientists who graduated in 1990 had 13.5 ± 12.5 publications, while MSTP physician scientists who graduated in 1975 had 51.2 ± 38.3 publications. Additionally, graduates from the Mayo Clinic's MD-PhD Program, the CI Program, and the NSRA Program had 18.2 ± 20.1, 26.5 ± 24.5, and 17.9 ± 26.3 publications, respectively. MSTP is a successful model for the training of physician scientists in the United States, but training at the postgraduate level also shows promising outcomes. An increase in the number of positions available for training at the postgraduate level should be considered. [ABSTRACT FROM AUTHOR]

Background: Terlipressin or octreotide given alone has been used as the first-line pharmacological treatment for acute variceal bleeding. In portal hypertensive animals, pre-infusion of octreotide followed by the addition of terlipressin has an additive or complementary effect on splanchnic hemodynamics. The current study was aimed at evaluating such a combination treatment in patients with cirrhosis and portal hypertension. Methods: Patients were randomly assigned to receive either a placebo (n = 11) or an intravenous infusion of octreotide 100 µg/h after an initial bolus of 100 µg (n = 13). Thereafter, each patient received an intravenous injection of terlipressin 2 mg. Hemodynamic values were measured basally, 30 min after octreotide or placebo, and 60 min after terlipressin. Results: Placebo administration did not affect any of the hemodynamic values. Terlipressin administration resulted in expected changes in hepatic venous pressure gradient, hepatic blood flow and systemic hemodynamics. In contrast, octreotide administration significantly decreased hepatic blood flow but did not affect other hemodynamic values. After terlipressin administration, significant hemodynamic changes were observed that were similar to the hemodynamic changes with terlipressin alone. The magnitude of changes in hepatic venous pressure gradient, cardiac index and systemic vascular resistance were no different between the two groups of patients. The heart rate was significantly lower in patients receiving octreotide plus terlipressin than those receiving terlipressin alone. Conclusion: The current study showed that a combination of octreotide and terlipressin did not exert an additive effect in reducing hepatic venous pressure gradient in patients with cirrhosis. In addition, the systemic hemodynamic changes were comparable between the two groups. [ABSTRACT FROM AUTHOR]

Background: 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 N[sup G]-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. Methods: Portal hypertension was induced by partial portal vein ligation (PVL). Rats were divided to receive either L-NAME (~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. Results: As compared with placebo-treated rats, chronic treatment with L-NAME in PVL rats significantly increased mean arterial pressure (P < 0.001) without modulating portal pressure (P > 0.05). In placebo-treated PVL rats, glypressin resulted in a less decrease in portal pressure in rats with bleeding than in those without bleeding (P < 0.05). For PVL rats with bleeding, the portal-hypotensive effect of glypressin was significantly potentiated after chronic L-NAME treatment (P < 0.05). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Endoscopic variceal ligation is widely accepted as the optimum endoscopic treatment for esophageal variceal hemorrhage. However, the rebleeding course and long-term outcome of patients with esophageal variceal hemorrhage after ligation have been poorly defined. Therefore, we conducted a long-term follow-up study to delineate the outcome of ligation and compare it with that after sclerotherapy. Methods: One hundred and eighty-five liver cirrhotic patients with endoscopically proven esophageal variceal hemorrhage were randomized to undergo endoscopic variceal sclerotherapy or ligation. These patients received regular follow-up and detailed clinical assessment. Results: Two patients developed hepatoma within 6 months of entry in each group and were excluded. Another six patients in the sclerotherapy group and seven patients in the ligation group were excluded because of poor compliance or lost to follow-up. Therefore, 84 patients in each group were analyzed. In this long-term follow-up (55.3 - 12.5 months) the rebleeding rate for ligation was lower than that for sclerotherapy, regardless of whether the rebleeding was analyzed by patient number or Kaplan-Meier analysis. With regard to the rebleeding risk of various periods, the sclerotherapy risk was higher than that of ligation within 4 weeks of the initial endoscopic treatment or before variceal eradication. Multifactorial analysis showed hematemesis, poor hepatic function, and sclerotherapy were the risk factors determining rebleeding. The annual hepatocellular carcinoma incidence was 4.9%. There was no difference in survival between sclerotherapy and ligation. Multifactorial analysis showed that poor hepatic function was the only factor determining survival. Conclusions: The rebleeding risk was higher in sclerotherapy than in ligation before variceal eradication, especially within 4 weeks of the initial endoscopic treatment. Long-term survival was dependent on hepatic reserve regardless of the treatment method. [ABSTRACT FROM AUTHOR]

Background: Spider angioma is a common sign in patients with liver cirrhosis, but the pathogenesis is still unclear. Alcohol and hyperestrogenemia are both possible etiologies. This study was designed to investigate the relationship of spider angiomas in patients with liver cirrhosis to alcohol, liver function test results, and plasma levels of sex hormones. Methods: Eighty-two patients with liver cirrhosis and 18 healthy subjects were enrolled in this study. The number, size, and location of the spider angiomas were recorded for all subjects. Plasma levels of estradiol and testosterone were measured. Results: Cirrhotic patients had significantly higher estradiol/testosterone ratios (26.8 ± 5.1 × 10[sup -3] versus 8.8 ± 2.0 × 10[sup -3]; P = 0.002) than healthy controls. Twenty-seven (33%) of the 82 cirrhotic patients had spider angiomas. Cirrhotic patients with spider angiomas were younger (56 ± 3 versus 66 ± 1 years; P = 0.002) and had higher serum bilirubin levels (3.3 ± 0.6 versus 1.7 ± 0.2 mg/dl; P = 0.002), longer prothrombin time (16.8 ± 0.8 versus 14.8 ± 0.4 sec; P = 0.01), and higher prevalence of alcoholism (41% versus 20%; P = 0.04) than those without. Stepwise logistic regression showed that alcoholism and serum bilirubin level were the only significant and independent predictors associated with the presence of spider angiomas in cirrhotic patients (odds ratio = 3.5; 95% confidence interval = 1.2-10.8; P = 0.03, and odds ratio = 2.8; 95% confidence interval = 1.3-5.7; P = 0.006, respectively). Conclusions: Alcoholism and impaired liver function are important predictors of the presence of spider angiomas in patients with liver cirrhosis. [ABSTRACT FROM AUTHOR]

Octreotide and propranolol are both effective portal hypotensive drugs in the control or prevention of variceal bleeding. The present study was undertaken to investigate the hemodynamic effects of octreotide and propranolol, alone or in combination, in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation. Portal hypertensive rats were allocated into one of the four groups: vehicle group (saline, 0.5 ml/day), octreotide group (100 microg/kg/12 hr), propranolol group (30 mg/kg/day), and octreotide (100 microg/kg/12 hr) plus propranolol (30 mg/kg/day) group. Propranolol or saline was administered by gavage, octreotide by subcutaneous injection. Drug was given one day before ligation and continued for eight consecutive days. Systemic as well as splanchnic hemodynamic parameters were measured thereafter. The portal venous pressure, portal tributary blood flow, and cardiac index were significantly reduced by octreotide, propranolol, or octreotide plus propranolol in portal hypertensive rats. Portal territory, systemic, and renal vascular resistances were significantly enhanced, while hepatic arterial blood flow significantly reduced, in the octreotide and octreotide plus propranolol groups as compared to vehicle group. Our results showed that eight-day administration of octreotide, propranolol, or octreotide plus propranolol led to portal hypotensive and antihyperdynamic effects in portal hypertensive rats. Overall, octreotide treatment alone resulted in better antihyperdynamic profiles than propranolol treatment alone. The combination of octreotide and propranolol offered no therapeutic benefits and was slightly less effective than octreotide alone. [ABSTRACT FROM AUTHOR]

Background: Terlipressin or octreotide given alone has been used as the first-line pharmacological treatment for acute variceal bleeding. In portal hypertensive animals, pre-infusion of octreotide followed by the addition of terlipressin has an additive or complementary effect on splanchnic hemodynamics. The current study was aimed at evaluating such a combination treatment in patients with cirrhosis and portal hypertension., Methods: Patients were randomly assigned to receive either a placebo (n = 11) or an intravenous infusion of octreotide 100 microg/h after an initial bolus of 100 microg (n = 13). Thereafter, each patient received an intravenous injection of terlipressin 2 mg. Hemodynamic values were measured basally, 30 min after octreotide or placebo, and 60 min after terlipressin., Results: Placebo administration did not affect any of the hemodynamic values. Terlipressin administration resulted in expected changes in hepatic venous pressure gradient, hepatic blood flow and systemic hemodynamics. In contrast, octreotide administration significantly decreased hepatic blood flow but did not affect other hemodynamic values. After terlipressin administration, significant hemodynamic changes were observed that were similar to the hemodynamic changes with terlipressin alone. The magnitude of changes in hepatic venous pressure gradient, cardiac index and systemic vascular resistance were no different between the two groups of patients. The heart rate was significantly lower in patients receiving octreotide plus terlipressin than those receiving terlipressin alone., Conclusion: The current study showed that a combination of octreotide and terlipressin did not exert an additive effect in reducing hepatic venous pressure gradient in patients with cirrhosis. In addition, the systemic hemodynamic changes were comparable between the two groups.

Background: Cyanoacrylate may form a barrier that prevents bacterial invasion when used in tissue. Because cyanoacrylate polymerizes within seconds on contact with aqueous media, it is used worldwide to arrest gastric variceal bleeding. The aim of this study was to determine the frequency of bacteremia after endoscopic cyanoacrylate injection for gastric variceal bleeding., Methods: Patients with cirrhosis who underwent endoscopic cyanoacrylate injection for gastric variceal bleeding were included. Patients with cirrhosis who underwent upper endoscopy for nonvariceal upper GI bleeding were recruited as controls. Patients with infection before endoscopy were excluded. Blood was cultured in both groups. Injection needles and endoscope accessory channels were cultured in the cyanoacrylate injection group., Results: More patients injected with cyanoacrylate had positive blood cultures in comparison with the control group (15/47 vs. 1/47, p < 0.0001). In the cyanoacrylate injection group, the volume of blood transfused and Child-Pugh score were factors associated with the occurrence of bacteremia. Most episodes of bacteremia were transient, except for 1 patient who died of sepsis. Most of the microorganisms cultured from blood samples were identical to those cultured from injection needles (65%) and accessory channels (90%)., Conclusions: Endoscopic cyanoacrylate injection for gastric varices does not limit the spread of bacteria. The endoscope accessory channel was the major source of bacteria. Most episodes of bacteremia were transient and uneventful.

Despite the suppression of glucagon release, an adaptive response aimed at maintaining vasodilatation after octreotide treatment may exist in portal hypertension. The present study was undertaken to evaluate the possible interaction between endothelium and non-endothelium-derived vasodilators after 1-wk octreotide administration in cirrhotic rats. Rats were allocated to receive either vehicle or octreotide (30 or 100 microg/kg every 12 h subcutaneously). Hemodynamic values, plasma glucagon levels, endothelium-related vasodilatory activities, and aortic endothelial nitric oxide synthase (eNOS) expression were determined after treatment. Octreotide administration decreased plasma glucagon and increased serum 6-keto-PGF(1 alpha) and NOx levels without affecting the hemodynamic values. In cirrhotic rats receiving octreotide, there was a blunt response to either L-NAME or indomethacin administration alone, but this blunt pressor response disappeared after simultaneous administration of the two drugs. Additionally, an increased aortic eNOS expression was observed in cirrhotic rats receiving 1-wk octreotide. It is concluded that 1-wk octreotide treatment did not correct the hemodynamic derangement in cirrhotic rats. The enhanced endothelium-related vasodilatory activity was noted after octreotide treatment that overcame the octreotide-induced hemodynamic effects in portal hypertension.

Background: Patients with unresectable hepatoma and acute esophageal variceal bleeding have extremely high rates of recurrent bleeding and mortality. This controlled study evaluates the feasibility and potential benefit of maintenance endoscopic variceal ligation in these patients., Methods: Patients with unresectable hepatoma and acute esophageal variceal bleeding underwent emergent endoscopic variceal ligation. After hemostasis, patients were randomized to undergo maintenance or esophageal variceal ligation (EVL) as necessary (demand ligation)., Results: Fifty-four patients underwent maintenance EVL and 55 demanded EVL. One or more subsequent EVL session could be performed in only 30 patients (55.6%) in the maintenance group (actual maintenance ligation). Logistic regression analysis found that hepatic function determines the feasibility of maintenance ligation (Child-Pugh's A+B vs. C, OR 23.00: 95% CI [5.26, 100.66]). The survival and recurrent bleeding rates were similar in both groups. A subgroup analysis of patients with Child-Pugh's A and B hepatic reserve in both the maintenance EVL group (n = 24) and demand EVL group (n = 25) was performed to assess the potential benefit of maintenance ligation. Maintenance ligation reduced the rate of recurrent bleeding compared with demand ligation (p = 0.043). Cox regression showed that portal vein thrombosis and tumors in both hepatic lobes were also factors together with EVL that determined recurrence of bleeding. Survival was similar in both groups., Conclusions: Maintenance ligation is feasible in patients with unresectable hepatoma and variceal hemorrhage if they have a good hepatic reserve. Maintenance ligation might lower the rate of recurrent bleeding in this subgroup of patients.

Background: Variceal ligation is the optimum endoscopic method for treating esophageal variceal bleeding. However, both early and multiple recurrences of esophageal varices frequently follow ligation. The aim of this randomized study was to determine whether a new, combined endoscopic "sandwich" method (i.e., ligation-sclerotherapy-ligation) could achieve better results than ligation alone., Methods: Ninety-four patients with cirrhosis and acute or recent esophageal variceal bleeding were randomized to undergo either the "sandwich" method or ligation alone (47 patients in each group)., Results: The sclerosant was retained in the varices for more than 30 minutes in 7 of 8 patients undergoing the "sandwich" method plus radiographic contrast medium. Active bleeding was controlled with this new method (9/9) as efficiently as ligation (12/12). The rate of recurrent bleeding was similar for both methods. Multivariate analysis showed the necessity for the use of antibiotics (odds ratio 3.95: 95% CI [1.60, 9.76]) to be an independent factor for recurrent bleeding. Two patients in the "sandwich" group developed strictures, but the frequency of other complications did not differ between the 2 groups. Kaplan-Meier analysis showed the cumulative probability of variceal recurrence was lower with the "sandwich" method (p = 0.0391). The survival rate and causes of death were similar in both groups., Conclusions: The "sandwich" method leads to longer retention of sclerosant in varices. This method is superior to ligation alone in terms of lower variceal recurrence rate and comparable to ligation with respect to hemostasis. However, it is unknown whether the lower recurrence rate of varices will persist long-term.

Objectives: Terlipressin reduces portal pressure in cirrhotic patients mainly through intense splanchnic vasoconstriction that decrease portal venous inflow. Hepatic blood flow may also be reduced by terlipressin. Prazosin (an alpha1-adrenoceptor antagonist) has also been proposed to decrease portal pressure in cirrhotic patients possibly through a decrease in the intrahepatic vascular resistance. The current study was aimed to evaluate whether a combination of prazosin and terlipressin exerts more beneficial effects than terlipressin alone., Methods: Patients were randomly assigned to receive either a placebo (n = 12) or an oral administration of prazosin 2 mg (n = 12). Thereafter, each patient received an intravenous injection of terlipressin 2 mg. Hemodynamic values were measured basally, 30 min after prazosin or placebo, and 30 min after terlipressin., Results: Placebo administration did not affect any hemodynamic values. Terlipressin administration, on the other hand, resulted in expected changes on the hepatic venous pressure gradient, hepatic blood flow, and systemic hemodynamics. In contrast, prazosin significantly decreased hepatic venous pressure gradient with an increased hepatic blood flow and intrinsic hepatic clearance. After terlipressin administration, a further decrease in hepatic venous pressure gradient was observed with preservation of hepatic blood flow and intrinsic hepatic clearance. The magnitude of decrease in hepatic venous pressure gradient was more profound in patients receiving prazosin plus terlipressin than in those receiving terlipressin alone. However, the magnitude of changes in systemic hemodynamics was no different between the two groups of patients., Conclusions: The current study showed that a combination of prazosin and terlipressin resulted in a more profound reduction of hepatic venous pressure gradient with a preservation of hepatic blood flow and intrinsic hepatic clearance than did terlipressin alone. However, the combined therapy did not modify the systemic hemodynamic effects exerted by terlipressin.

Portopulmonary hypertension is now recognized as one of the pulmonary complications of chronic liver disease. However, previous studies reported that the incidence ranged from 0.25% to 2%, excluding fortuitous coincidence. In this study, we aimed to determine the variant hemodynamic and clinical features of portopulmonary hypertension in an area with a high prevalence of viral cirrhosis. After reviewing the hemodynamic data of 322 patients with portal hypertension admitted to the Taipei Veterans General Hospital between 1987 and 1999, we found 10 with portopulmonary hypertension. The overall incidence was, therefore, 3.1% in all patients with portal hypertension. Most of the patients with portopulmonary hypertension experienced exertional dyspnea. The survival times ranged from 2 to 86 months. In our series, most of the patients who died, died of complications related to cirrhosis and portal hypertension, but not of complications related to pulmonary hypertension. This study suggested that portopulmonary hypertension was not a frequent complication in cirrhotic patients and was not associated with an adverse outcome.

Ticlopidine is a commonly prescribed drug in cerebrovascular or cardiovascular diseases. Since the first introduction in 1970's, ticlopidine was shown to be a relatively safe drug. The adverse effects of ticlopidine were mainly bone marrow toxicity and elevation of liver function tests. Ticlopidine-induced hepatitis is rare and only 33 cases were reported in previous English literature. The 33 cases were mostly categorized in cholestatic liver injury; only 2 cases were hepatocellular. In Taiwan, a case of ticlopidine-induced cholestatic hepatitis was ever reported. Herein, we present another rare case of ticlopidine-induced hepatitis in Taiwan with the nature of hepatocellular injury.