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Biomedical subjects

F Y Lee

Publications and source records attributed to F Y Lee.

At least 37 records · Page 2Linked to original sources

An all-arthroscopic soft-tissue balancing technique for lateral patellar instability.

Patellar realignment procedures for lateral patellar instability often involve open approaches to imbricate the medial soft tissues. We present a technique to balance the soft tissues to correct lateral patellar instability that is performed entirely arthroscopically. A retinacular release is performed laterally and the soft tissues are imbricated medially using arthroscopic suture passing and knot tying techniques.

Arthroscopy↗

Endothelin-1 induces vasoconstriction on portal-systemic collaterals of portal hypertensive rats.

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 <.05). Incubation with NNA, INDO, or both significantly enhanced the response of collaterals to ET-1 (P < .05). These results show that ET-1 produces a direct vasoconstrictive effect on the collateral vessels of portal hypertensive rats. This effect is mediated by ET(A,) but not ET(B), receptors. Both nitric oxide and prostaglandin modulate the collateral vascular response to ET-1 and may therefore participate in the development and maintenance of portal hypertension.

Animals↗

A new "sandwich" method of combined endoscopic variceal ligation and sclerotherapy versus ligation alone in the treatment of esophageal variceal bleeding: a randomized trial.

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.

Combined Modality Therapy↗

Feasibility and potential benefit of maintenance endoscopic variceal ligation in patients with unresectable hepatocellular carcinoma and acute esophageal variceal hemorrhage: a controlled trial.

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.

Acute Disease↗

Bacteremia after endoscopic injection of N-butyl-2-cyanoacrylate for gastric variceal bleeding.

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.

Bacteremia↗

Hemodynamic effects of a combination of prazosin and terlipressin in patients with viral cirrhosis.

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.

Antihypertensive Agents↗

Adaptive vasodilatory response after octreotide treatment.

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.

6-Ketoprostaglandin F1 alpha↗

Placental compliance during fetal extracorporeal circulation.

The fetus requires large amounts of volume when weaning from cardiac bypass. This suggests that placental vasculature can act as a large capacitor in the fetal circulation. To assess placental compliance of fetal lambs, seven isolated in situ lamb placentas were placed on extracorporeal circulation. Umbilical artery blood flow was varied from 0 to 350 ml. min(-1). kg fetal wt(-1). Because the extracorporeal circuit is a closed system, volume changes in the placenta induced by umbilical artery pressure changes were measured from reciprocal volume changes in the reservoir. There was a wide range of change in absolute volume of blood within the fetal placental compartment (216.4 +/- 29.3 ml). Placental compliance was linear over the entire range of pressure changes exerted on the placental vasculature (r(2) = 0.83, P = 0.0001). This indicates that the placenta is a unique and sensitive capacitor in the fetal circulation. This information is important clinically because it establishes that aggressive resuscitation of the fetus using volume may be necessary when weaning the fetus from cardiac bypass.

Animals↗

BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy.

BMS-247550, a novel epothilone derivative, is being developed by Bristol-Myers Squibb Company (BMS) as an anticancer agent for the treatment of patients with malignant tumors. BMS-247550 is a semisynthetic analogue of the natural product epothilone B and has a mode of action analogous to that of paclitaxel (i.e., microtubule stabilization). In vitro, it is twice as potent as paclitaxel in inducing tubulin polymerization. Like paclitaxel, BMS-247550 is a highly potent cytotoxic agent capable of killing cancer cells at low nanomolar concentrations. Importantly, BMS-247550 retains its antineoplastic activity against human cancers that are naturally insensitive to paclitaxel or that have developed resistance to paclitaxel, both in vitro and in vivo. Tumors for which BMS-247550 demonstrated significant antitumor activity encompass both paclitaxel-sensitive and -refractory categories, i.e., (a) paclitaxel-resistant: HCT116/VM46 colorectal (multidrug resistant), Pat-21 breast and Pat-7 ovarian carcinoma (clinical isolates; mechanisms of resistance not fully known), and A2780Tax ovarian carcinoma (tubulin mutation); (b) paclitaxel-insensitive: Pat-26 human pancreatic carcinoma (clinical isolate) and M5076 murine fibrosarcoma; and (c) paclitaxel sensitive: A2780 ovarian, LS174T, and HCT116 human colon carcinoma. In addition, BMS-247550 is p.o. efficacious against preclinical human tumor xenografts grown in immunocompromised mice or rats. Schedule optimization studies indicate that BMS-247550 is efficacious when administered frequently (every 2 days x 5) or intermittently (every 4 days x 3 or every 8 days x 2). These efficacy data demonstrate that BMS-247550 has the potential to surpass Taxol in both clinical efficacy and ease of use (i.e., less frequent treatment schedule and/or oral administration).

Administration, Oral↗

Preclinical pharmacology of BMS-275183, an orally active taxane.

BMS-275183 is a taxane, the mechanism of action of which is like other known taxanes, and is the polymerization of tubulin. BMS-275183 given p.o. was as effective as i.v. paclitaxel in five tumor models [murine M109 lung and C3H mammary 16/C, and human A2780 ovarian (grown in mice and rats) and HCT/pk colon]. It was active in one other tumor model (human HCT-116 colon) but inferior to parenteral paclitaxel. BMS-275183 given p.o. was active in a human, hormone-dependent, prostate tumor model, CWR-22, and just as effective as anti-androgen chemotherapy. In a schedule dependency study, increasing the interval of time between oral administrations resulted in greater cumulative dose tolerance and improved therapeutic outcome. Oral BMS-275183 was evaluated as a combination therapy in conjunction with i.v. paclitaxel. Therapeutic advantages were evident for tumor-bearing mice that received the oral taxane either after induction chemotherapy or between courses of such treatment. BMS-275183 is currently in Phase I clinical trials at multiple sites.

Administration, Oral↗

Hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic failure: role of endotoxin and tumor necrosis factor-alpha.

BACKGROUND: Hepatic encephalopathy, a complex neuropsychiatric syndrome secondary to acute liver failure, chronic parenchymal liver disease or portal-systemic shunting, may possibly develop through mediators of endotoxin and tumor necrosis factor-alpha (TNF-alpha). However, there are no published data concerning the relationships between the severity of encephalopathy and the plasma levels of endotoxin and TNF-alpha. METHODS: Male Sprague-Dawley rats weighing about 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection ofthioacetamide (350 mg/kg/day) for 3 consecutive days. Severity of encephalopathy was assessed by measuring motor counts using an Opto-Varimex animal activity meter. Plasma levels of endotoxin and TNF-alpha were determined by chromogenic Limulus assay and ELISA method, respectively. RESULTS: Our study revealed that higher plasma levels of endotoxin (> 5.9 pg/ml) and TNF-alpha (> 18.8 pg/ml) were significantly associated with more blunted motor activities in rats with fulminant hepatic failure (p < 0.05). A significant correlation was observed between plasma concentrations of endotoxin and TNF-alpha (r = 0.59, p < 0.001). Plasma levels of endotoxin were weakly correlated with the total movements in an open field (r = -0.34, p = 0.032) and the counts of ambulatory (r = -0.38, p = 0.014) and vertical movements (r = -0.40, p = 0.010). There were no correlations between the motor counts and plasma levels of TNF-alpha (p > 0.05). CONCLUSIONS: In addition to endotoxin and TNF-alpha, other factors may participate in the pathogenesis of hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic failure.

Animals↗

Discovery of (R)-7-cyano-2,3,4, 5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3- (phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine (BMS-214662), a farnesyltransferase inhibitor with potent preclinical antitumor activity.

Continuing structure-activity studies were performed on the 2,3,4, 5-tetrahydro-1-(imidazol-4-ylalkyl)-1,4-benzodiazepine farnesyltransferase (FT) inhibitors. These studies demonstrated that a 3(R)-phenylmethyl group, a hydrophilic 7-cyano group, and a 4-sulfonyl group bearing a variety of substituents provide low-nanomolar FT inhibitors with cellular activity at concentrations below 100 nM. Maximal in vivo activity in the mutated K-Ras bearing HCT-116 human colon tumor model was achieved with analogues carrying hydrophobic side chains such as propyl, phenyl, or thienyl attached to the N-4 sulfonyl group. Several such compounds achieved curative efficacy when given orally in this model. On the basis of its excellent preclinical antitumor activity and promising pharmacokinetics, compound 20 (BMS-214662, (R)-7-cyano-2,3,4, 5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thie nyl sulfonyl)-1H-1,4-benzodiazepine) has been advanced into human clinical trials.

3T3 Cells↗

Experimental model for allograft incorporation and allograft fracture repair.

This study describes a rat model of allograft osteotomy healing. An intercalary skeletal defect was created in adult Lewis rats by resecting a 2-cm segment of the femur in the diaphysis, including the periosteum and the cuff of muscle layers. The skeletal defects were replaced with fresh-frozen devascularized intercalary allografts from Sprague-Dawley rats. A transverse osteotomy was made in the middle of the allograft. The osteotomized segments were stabilized with an intramedullary threaded Kirschner wire, which allowed immediate ambulation. Radiographic and histological examination at 4 and 8 weeks revealed a characteristic healing process at three different interfaces. Radiographically, the distal metaphyseal host-donor junction healed faster than the proximal diaphyseal host-donor interface. The osteotomy site did not have evidence of an intramembranous or endochondral repair process. This model can serve as a baseline for assessing allograft incorporation and fracture repair.

Animals↗

Profiles of gonadal development, sex steroids, aromatase activity, and gonadotropin II in the controlled sex change of protandrous black porgy, Acanthopagrus schlegeli Bleeker.

The objectives of the present study were to investigate the effects of oral administration of estradiol-17 beta (E(2)) on the sex steroids and gonadotropin II (GTH II) in plasma, aromatase activity in gonad and brain, and sex change in protandrous black porgy, Acanthopagus schlegeli Bleeker. Two-year-old black porgy were divided into two groups, one fed a control diet and the other a diet mixed with E(2) (4.0 mg/kg feed) for 7 months. Significantly higher GSI was observed in the E(2) group. Fish treated with E(2) showed complete suppression of spermatogenesis and spermiation and induced sex change with vitellogenic oocytes and large primary oocytes. Lower levels of plasma 11-ketotestosterone and higher levels of plasma vitellogenin were shown in the E(2) group. Higher gonadal aromatase activity in concordance with elevated plasma levels of GTH II was observed in the E(2) group. The highest aromatase activity in the forebrain in the control group was observed in January. Higher aromatase activity in forebrain, midbrain, and hindbrain was also detected in the E(2) group than the control group. The change of aromatase activity in brain was more susceptible than that in gonad. The data showed that the increase of plasma GTH II levels and gonadal aromatase activity may be important to the controlled sex change by administration in black porgy.

Animals↗

Preclinical oral antitumor activity of BMS-185660, a paclitaxel derivative.

PURPOSE: A water soluble paclitaxel derivative, BMS-185660, identified previously as having parenteral activity comparable with that of the parent drug, was evaluated for antitumor activity when given orally. METHODS: Staged subcutaneous (s.c.) tumor models of both murine and human origin were used for this purpose. RESULTS: BMS-185660 achieved levels of activity following oral administration which were comparable with those maximum effects obtained using intravenous (i.v.) paclitaxel. Consecutive daily oral administrations of BMS-185660 resulted in maximum gross log cell kill (LCK) values of 1.7-2.0 in two experiments involving the s.c. Madison 109 murine lung tumor model, which were comparable with the best effects of the derivative injected intravenously, and 0.3 to 0.9 LCK greater than the maximum effects obtained with i.v. paclitaxel; paclitaxel given orally was inactive. Against a human ovarian tumor model with developed resistance to cisplatin (A2780/ cDDP), oral BMS-185660 achieved a maximum LCK of 1.8 compared with i.v. paclitaxel, which produced a maximum 2.4 LCK. Also, in the human HCT-116 colon carcinoma model, oral BMS-185660 cured a maximum of seven of eight mice compared with six of seven mice cured with i.v. paclitaxel. The loss in potency between comparably effective intravenously and orally administered doses of BMS-185660 was about four- to five-fold, but since no drug-associated lethality was ever observed following the oral administration of the highest doses of BMS-185660, further dose escalation may have been tolerated. The intermediate metabolite between BMS-185660 and paclitaxel is BMS-181681. This compound was also evaluated orally and found not to be active versus s.c. M109, despite demonstrating good activity by the i.v. route. CONCLUSION: The comparable activities of both intravenously and orally administered BMS-185660 to intravenously administered paclitaxel, combined with the attribute of improved water solubility, provides a good basis for further derivative development.

Administration, Oral↗

Recurrence of esophageal varices following endoscopic treatment and its impact on rebleeding: comparison of sclerotherapy and ligation.

BACKGROUND/AIMS: Endoscopic variceal ligation is superior to sclerotherapy because of its lower rebleeding and complication rates. However, ligation is not without drawbacks due to a higher tendency to variceal recurrence. We conducted a randomized cohort study to delineate the long-term history of variceal recurrence following ligation and sclerotherapy, and to clarify the impact of recurrence on rebleeding and on the consumption of endoscopic treatment resources. METHODS: Two hundred cirrhotic patients with esophageal variceal bleeding were randomized to undergo maintenance endoscopic variceal sclerotherapy or ligation. RESULTS: One hundred and forty-one patients achieved variceal eradication and were regularly followed up for 2.2 to 6.7 (mean: 5.1 +/- 1.2) years. The demographic data, hepatic reserve, bleeding severity, and endoscopic features of both sclerotherapy (n=70) and ligation (n=71) showed no difference. Forty (57.1%) patients who underwent sclerotherapy experienced 58 recurrences of esophageal varices, in contrast to the 46 (64.8%) patients who underwent ligation and experienced 81 episodes of recurrence. Kaplan-Meier analysis showed that within 2 years variceal recurrence was more frequent for ligation than sclerotherapy, and the difference decreased thereafter. Multiple recurrence appeared more common with ligation (1/2/3/4/5 episodes of recurrence: 46/23/8/3/1 vs. 40/14/3/1/0, p=0.08). On multifactorial analysis, the endoscopic treatment method and red wale markings were the two factors determining variceal recurrence. Rebleeding from recurrent esophageal varices was unusual and showed no difference between the two groups (7/58 vs. 6/81, p>0.05). Rebleeding from gastric varices was more common after eradication by sclerotherapy (7/19 vs. 1/16, p=0.085) than by ligation. The number of sessions required for eradication of recurrent varices was no different between the two groups. CONCLUSIONS: Early recurrence and multiple recurrence of esophageal varices are more likely in patients undergoing endoscopic ligation, compared to sclerotherapy; however, the recurrence did not lead to a higher risk of rebleeding or require more endoscopic treatment.

Aged↗

Evaluation of gallbladder motility in patients with liver cirrhosis: relationship to gallstone formation.

To investigate the postprandial gallbladder motility, including emptying and refilling, in cirrhotic patients and to evaluate the relationship to the presence of gallstones and various humoral mediators, 82 patients with liver cirrhosis and 40 age- and sex-matched healthy subjects were enrolled into this study. Postprandial gallbladder volumes were measured with ultrasonography every 15 min for 2 hr. Plasma levels of estradiol, testosterone, substance P, and nitrate/nitrite were also measured. Cirrhotic patients showed a higher prevalence of gallstones than healthy subjects (41% vs 15%, P = 0.003), and the prevalence increased with the progression of liver cirrhosis (Child-Pugh class A: 26%, B: 44%, and C: 65%, P = 0.02). Plasma levels of estradiol, testosterone, and substance P, and nitrate/nitrite and estradiol/testosterone ratios were not different between cirrhotic patients with and without gallstones. However, postprandial refilling of the gallbladders was significantly impaired in patients with cirrhosis, especially in those combined with gallstones. There was no significant difference in the postprandial gallbladder motility between cirrhotic patients with and without elevated plasma levels of estradiol, testosterone, and substance P and nitrate/nitrite, and estradiol/testosterone ratios. Gallstones were common in patients with liver cirrhosis and the prevalence increased with the progression of liver diseases. Sex hormones, substance P, and nitrate/nitrite did not play major roles in the formation of gallstones in cirrhotic patients. Refilling of the gallbladder was significantly impaired in patients with liver cirrhosis, especially in those with gallstones, and may play an important role in the pathogenesis of gallstones.

Aged↗