Development of a nursing-specific Mini-CEX and evaluation of the core competencies of new nurses in postgraduate year training programs in Taiwan.

BACKGROUND: Modern nursing requires a broad set of academic and practical skills, and an effective nurse must integrate these skills in a wide range of healthcare contexts. Cultivation of core competencies has recently become a key issue globally in the development of nursing education. To assess the performance of new nurses, this study developed a nursing-specific Mini-Clinical Evaluation Exercise (Mini-CEX) to evaluate the effect of postgraduate year (PGY) nurse training programs in Taiwan. METHODS: A nursing-specific Mini-CEX was developed based on the required core competencies of nurses. Reliability and validity were confirmed in evaluator workshops carried out prior to the administration of the pilot test and final test. Thirty-two PYG trainees were recruited with a supervisor-to-trainee ratio of 1:1.94. Data were collected from February to June 2012 and analyzed using the Kruskal-Wallis test. RESULTS: The 32 PGY trainees scored highest in the "nursing professionalism" dimension and the lowest in the "physical examination" dimension. The overall competency score was satisfactory. The trainee nurses with 19-24 months of experience scored higher than the other two groups in overall performance. CONCLUSION: The results of this research indicate the feasibility of using our Mini-CEX tool to evaluate the competencies of PGY trainees.

The development and use of a pharmacist-specific Mini-CEX for postgraduate year trainees in Taiwan.

BACKGROUND: Clinical pharmacists must have a complex combination of academic knowledge and practical experience that integrates all aspects of practice. Taiwan's Ministry of Health and Welfare in 2007 launched the Postgraduate Year (PGY) training program to increase the standard of pharmaceutical care. This study aims to develop a pharmacist-specific Chinese-language Mini-Clinical Evaluation Exercise (Mini-CEX) to evaluate the professional development of postgraduate year trainees. METHOD: The specialized Mini-CEX was developed based on the core competencies of pharmacists, published literature, and expert opinion. A pilot test and evaluator workshop were held prior to the administration of the main test. Fifty-three samples were recruited. The main study was conducted at two regional teaching hospitals and a medical center teaching hospital in Taiwan between February and June 2012. The results were analyzed with the kappa statistic (inter-rater reliability) and descriptive statistics, while the Kruskal-Wallis test was used to examine the PGY trainees' Mini-CEX scores based on their performances. RESULTS: Trainees who had recently completed PGY programs (C-PGY) and 2nd year PGY trainees (PGY2) earned excellent scores, while the 1st year PGY trainees (PGY1) earned satisfactory scores in overall performance. C-PGY and PGY2 trainees also performed significantly better than PGY1 trainees in the organization and efficiency domain, and the communication skills domain. CONCLUSION: This study demonstrates the feasibility of using the newly developed pharmacist-specific Chinese-language version of the Mini-CEX instrument to evaluate the core competencies of PGY trainees in clinical settings.

An integrative OSCE methodology for enhancing the traditional OSCE program at Taipei Medical University Hospital--a feasibility study.

BACKGROUND: Continuous development and use of new technologies and methodologies are key features in improving the learning, performance, and skills of medical students and students of all health care professions. Although significant improvements in teaching methodologies have been made in all areas of medicine and health care, studies reveal that students in many areas of health care taking an objective structured clinical examination (OSCE) express difficulties. Thus, this study was planned as a feasibility study to assess the educational effectiveness of an integrated objective structured clinical examination (iOSCE) using both standardized patients and virtual patients. METHODS: Thirty (30) medical students in their first year of internship at Taipei Medical University volunteered to be part of a feasibility study for demonstrating the concept of iOSCE. They divided themselves into five groups of six students each and were requested to evaluate two cases: 1) a patient with abdominal pain and 2) a patient with headache using a combination of a standardized patient and a virtual patient. For each of the two cases, five stations were designed in which students were given ten minutes per station leading to a final diagnosis and concluded with a debriefing. The five stations were: Station 1) Interacting with the standardized patient. Station 2) Writing the patient note and developing a differential diagnosis. Station 3) Selecting appropriate laboratory and imaging studies. Station 4) Making a final diagnosis and stating the evidence for it. Station 5) Having the debriefing. Each group of 6 students was assigned 2 hours per day for each case. All participants completed a survey regarding the usefulness and efficiency of the iOSCE. RESULTS: All medical students (30/30; 100%) found the iOSCE program to be very satisfactory, and all expressed that they would like to have further iOSCE experiences if given the opportunity. In terms of ease and helpfulness, the students rated the program an average of 4.4 for the 1st case (abdominal pain) and 4.5 for the 2nd case (headache) on a scale of 1-5, with 5 being the highest and 1 being the lowest score. CONCLUSIONS: The participants felt that the iOSCE program can offer certain advantages over the traditional OSCE with the SP alone. They cited that the iOSCE provided improved clarity of what was being assessed as well as providing an opportunity to improve their diagnostic reasoning.

Portosystemic collaterals are not prerequisites for the development of hepatic encephalopathy in cirrhotic rats.

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.

Pravastatin for thioacetamide-induced hepatic failure and encephalopathy.

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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 H&E 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. CONCLUSIONS: Pravastatin ameliorates hepatic encephalopathy and liver biochemistry and improves survival in rats with acute liver failure, but not in those with cirrhosis.

Professional development is enhanced by serving as a mini-CEX preceptor.

INTRODUCTION: The mini-clinical evaluation exercise (mini-CEX) is widely used for the evaluation of medical trainees' clinical competence. To our knowledge, no study has examined the effect of mini-CEX on the preceptors. Based on the principle of "to teach is to learn twice," we hypothesized that the act of precepting a mini-CEX would enhance preceptors' own learning and performance. METHODS: A 21-item questionnaire incorporating the 3 out of 4 levels of Kirkpatrick's model was completed by experienced mini-CEX preceptors. Data collected from the questionnaire included ratings of Kirkpatrick's level of "Reaction" (level 1) and "Behavior" (level 3) and the frequencies of relearning the clinical skills related to mini-CEX, which assessed Kirkpatrick's "Learning" (level 2). RESULTS: A majority of the respondents either strongly agreed or agreed that precepting the mini-CEX both increased reflection on their own clinical practice and had a positive impact on their clinical skills. More than 80% of preceptors reported relearning one or more of the mini-CEX clinical skills. Experienced preceptors relearned the clinical skills more frequently than the less experienced preceptors. About one-third of respondents indicated that being a preceptor of mini-CEX increased both self-confidence and health care quality in their own clinical practice. DISCUSSION: These findings provide preliminary evidence suggesting that participating as a preceptor in a mini-CEX has a positive impact on the preceptor's professional development. Further studies are needed, including analyzing mechanisms of mini-CEX on the clinical skills of preceptor, and assessing whether similar effects can be observed in other teaching hospitals in different cultural contexts.

Kinetics of cytokine expression in cirrhotic rats.

BACKGROUND: Cytokines are involved in liver injury and cirrhosis and systemic and hepatic cytokine levels may help predict cirrhosis evolution. However, the relevant survey has not been performed. METHODS: Male Sprague-Dawley rats (240-270 g) received either common bile duct ligation (BDL, animal model of cholestatic liver injury) or sham operation (control). Five rats were sacrificed and liver and serum were collected from each in weeks 1, 2, 4, 6, 8 and 10 after surgery. Hepatic expression of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) were analyzed by immunohistochemial staining. The corresponding serum levels were measured by ELISA. RESULTS: Compared to the corresponding sham groups, hepatic expression of these cytokines in BDL rats was significantly and progressively enhanced during cirrhosis development. However, serum IFN-γ levels of BDL rats did not change significantly. Serum TNF-α of BDL rats increased gradually and reached a peak in week 6. Serum TGF-ß level was elevated up to week 8, whereas IL-10 level decreased progressively until week 6. CONCLUSION: Cirrhosis development in BDL rats is associated with progressively enhanced expression of hepatic pro-inflammatory and anti-inflammatory cytokines, which is not in accord with the corresponding serum concentration. The circulating cytokine concentration may not totally reflect the hepatic expression level throughout the development of cirrhosis.

Selective cyclooxygenase inhibition improves hepatic encephalopathy in fulminant hepatic failure of rat.

Prostaglandin plays an important role in the pathogenesis of hepatic encephalopathy. This study investigated the therapeutic effects of selective cyclooxygenase (COX) inhibitor on hepatic encephalopathy in thioacetamide-induced fulminant hepatic failure (FHF) rats. The selective COX-1 inhibitor (SC-560), COX-2 inhibitor (NS-398) or distilled water (control) was administered in the normal and FHF rats. The mortality rates were calculated and severity of hepatic encephalopathy was evaluated using Opto-Varimex activity sensors. Besides, the levels of blood ammonia, 6-keto-prostaglandin-F(1α) (PGF(1α), active metabolite of prostacyclin), tumor necrosis factor α (TNF-α) and liver biochemistry tests were measured. The hepatic mRNA expressions of nitric oxide synthase and COX were determined, and the liver histopathological changes were examined. The liver biochemistries and motor activities were similar among COX-1, COX-2 treated and control groups. SC-560 treatment improved the survival of FHF rats (mortality rates: SC-560 group 0%, control 33%; P=0.037). Besides, SC-560 treatment improved hepatic encephalopathy and decrease plasma levels of PGF(1α), but did not change TNF-α levels. There were no significant differences in liver biochemistry and ammonia levels except that the aspartate aminotransferase levels were lower in the NS-398 treated group. Both hepatic COX-1 and COX-2 mRNA expressions were attenuated after SC-560 treatment. The decreased COX-2 and increased constitutive nitric oxide synthase mRNA expressions were found after NS-398 treatment. Besides, the histopathology of liver got improved after selective COX inhibition. In conclusion, COX-1 inhibition by SC-560 decreases the mortalities and improves motor activities, suggesting COX-1, rather than COX-2, plays a major role in hepatic encephalopathy of FHF rats.

Assessment of clinical competence of medical students using the objective structured clinical examination: first 2 years' experience in Taipei Veterans General Hospital.

BACKGROUND: Competence-oriented education is currently the mainstream method of teaching clinical medical education. The objective structured clinical examination (OSCE) is a widely employed and accepted tool to measure the clinical competence of medical students. We describe the first 2 years' experience of OSCE in Taipei Veterans General Hospital. METHODS: At Taipei Veterans General Hospital, every 7(th)-year medical student has taken the OSCE since 2006. There were 15 stations in the first 2 years' OSCEs. In years 1 and 2, 133 and 132 students were assessed by the OSCE, respectively. The content of the OSCE included internal medicine, surgery, pediatrics, obstetrics and gynecology, communication, and emergency training. All categories and results of examinees' evaluation at each station were recorded inclusively and compared statistically. RESULTS: The average scores of students from the 15 stations ranged from 47.7 ± 16.4 to 93.7 ± 8.5 in 2007. The score for communication skills was the lowest, whereas the score for Micro-Sim was the highest. Communication skills and electrocardiography interpretation were the 2 categories in which most of the students failed. A reliability analysis was conducted of the 2007 OSCE questions. The overall score and reliability (Cronbach's reliability) was 0.641. The difference between the impacts on reliability after deleting a test item ranged from 0.59 to 0.65 for all stations. This meant that every station had a similar impact on reliability after being deleted. The squared multiple correlation, R(2), of the reliability of each item was between 0.12 and 0.49, with chest X-ray interpretation being the lowest. The item-total correlation was between 0.10 and 0.41, with interactive case being the lowest. CONCLUSION: The OSCE is an effective method for assessing the clinical competence of medical students. The OSCE could be improved further by modifying the examination questions and promoting effective training for standardized patients and examiners.

Lack of therapeutic effects of gabexate mesilate on the hepatic encephalopathy in rats with acute and chronic hepatic failure.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

New simulation-based airway management training program for junior physicians: Advanced Airway Life Support.

BACKGROUND: All junior physicians in Taiwan were enrolled into a 3-month post-graduate year 1 (PGY1) course after Severe Acute Respiratory Syndrome (SARS) attack in 2003. AIMS: To develop and evaluate a new airway management training protocol by using an integrated course of lectures, technical workshops and medical simulations. METHODS: In each PGY1 course, the trainees participated in the Advanced Airway Life Support (AALS) program. After 2 h lecture, the trainees were divided into three groups for 4 h technical workshop, including 10 skill stations and medical simulation at the Clinical Skills Resources Center of the hospital at different times. Video-based debriefing and feedback were performed after each simulation. The same scenario was re-simulated after debriefing. Participants' performance was assessed by single global rating and a 5 key actions scoring. RESULTS: A total of 266 junior physicians have been trained with this AALS programs in 2 years. They learned the techniques of airway management, passed the performance checklist of technical workshop, and received higher scores during re-simulation regardless of scoring methods. CONCLUSIONS: The AALS training program can provide methodical and systematic training for junior residents to mature with specialized technical skills and higher-order cognitive skills, behaviors and leadership in airway management.

Simvastatin for rats with thioacetamide-induced liver failure and encephalopathy.

BACKGROUND AND AIM: Nitric oxide (NO) inhibition aggravates hepatic damage and encephalopathy and increases mortality in rats with thioacetamide (TAA)-induced acute liver failure. Statins enhance NO synthase expression beyond their lipid-lowering capability, but the impact on encephalopathy remains unexplored. The aim of this study was to assess the effects of simvastatin on rats with TAA-induced acute liver damage and hepatic encephalopathy. METHODS: Sprague-Dawley rats received TAA (350 mg/kg/day) or normal saline (NS) by intraperitoneal injection for 3 consecutive days. Two days before injections, each group was divided into three subgroups, taking (i) distilled water; (ii) simvastatin (20 mg/kg/day); or (iii) simvastatin plus N(G)-nitro-l-arginine methyl ester (L-NAME, 25 mg/kg/day) by oral gavage for 5 days. On the fifth day, severity of encephalopathy was assessed and plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and ammonia were measured. RESULTS: The TAA subgroups showed higher ALT, AST, bilirubin and ammonia levels and lower motor activity counts as compared with the NS subgroups. Among the TAA-treated subgroups, rats with simvastatin treatment exerted higher motor activity counts and survival rate (P = 0.043), and a trend of lower ALT, AST, bilirubin and ammonia levels than those receiving saline. All rats that underwent simvastatin plus L-NAME treatment died during or after TAA injections. CONCLUSIONS: Simvastatin improved encephalopathy and survival in TAA-administered rats. The beneficial effect was offset by L-NAME, suggesting the role of NO in liver damage and encephalopathy.

Zhi-fuzi, a cardiotonic Chinese herb, a new medical treatment choice for portal hypertension?

Zhi-Fuzi (Radix Aconiti lateralis preparata) is prescribed fairly frequently in Chinese medicine clinical practice for treating the complications of cirrhosis. However, scientific evidence regarding its efficacy and safety has not been available until now; in addition, its treatment efficacy has not yet been evaluated in well-designed clinical trials. Hence, we investigated the hemodynamic effects of Zhi-Fuzi in conscious rats with portal vein ligation (PVL) and the safety in normal rats. Our study included 3 parts: (i) early administration during which the hemodynamic effects of low and high doses of Zhi-Fuzi (0.4 and 0.8 g/kg twice daily) and propranolol (15 and 30 mg/kg twice daily) administered for 14 days after PVL on male Sprague-Dawley rats were evaluated; (ii) late administration during which the other group of PVL rats received 2.4 g/kg of Zhi-Fuzi twice daily from the 15th to 28th postoperative day; hemodynamic effects were measured when the Zhi-Fuzi treatment was finished; and (iii) safety evaluation during which 2 groups of normal rats were administered Zhi-Fuzi (0.4 and 0.8 g/kg twice daily) for 14 days; biochemical and histopathologic studies were completed after hemodynamic measurement. In early administration the portal pressures in rats receiving low and high doses of Zhi-Fuzi, low and high doses of propranolol, and distilled water were 13.81 +/- 0.11, 11.59 +/- 0.07, 17.09 +/- 0.06, 14.52 +/- 0.29, and 20.11 +/- 0.22 mm Hg, respectively. The high dose of Zhi-Fuzi exerted more portal hypotensive effects than propranolol and simultaneously ameliorated the systemic arterial hypotension in PVL rats. The late administration of Zhi-Fuzi also significantly reduced the elevated portal pressure (14.56 +/- 0.19 vs. 19.50 +/- 0.31 mm Hg in control, P < 0.05). There were no adverse effects seen in normal rats receiving Zhi-Fuzi. The results suggest that Zhi-Fuzi is a potential drug for the prophylaxis and treatment of portal hypertension.

Role of hepatic nitric oxide synthases in rats with thioacetamide-induced acute liver failure and encephalopathy.

BACKGROUND: Hepatic encephalopathy is neuropsychiatric derangement secondary to hepatic decompensation or portal-systemic shunting. Nitric oxide (NO) synthase inhibition aggravates encephalopathy and increases mortality in rats with thioacetamide (TAA)-induced acute liver failure, suggesting a protective role of NO. This study investigated the roles of endothelium-derived constitutive NO synthase (eNOS) and inducible NOS (iNOS) in the liver of rats with fulminant hepatic failure and encephalopathy. METHODS: Male Sprague-Dawley rats (300-350 g) were randomized to receive TAA 350 mg/kg/day, by intraperitoneal injection or normal saline for 3 days. Severity of encephalopathy was assessed with the Opto-Varimex animal activity meter. Plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin were measured. Hepatic iNOS and eNOS RNA and protein expressions were assessed by reverse transcription-polymerase chain reaction and Western blot analyses, respectively. RESULTS: The TAA group showed lower motor activity counts than the normal saline group. Hepatic eNOS, but not iNOS, mRNA and protein expressions were enhanced in the TAA group. In addition, hepatic eNOS mRNA expression was negatively correlated with total movement but positively correlated with ALT and AST. Protein expression of hepatic eNOS was positively correlated with ALT, AST and bilirubin. CONCLUSION: Upregulation of hepatic eNOS was observed in rats with TAA-induced fulminant hepatic failure and encephalopathy, which might play a regulatory role.

Methimazole alleviates hepatic encephalopathy in bile-duct ligated cirrhotic rats.

BACKGROUND: Acute or chronic liver damage may lead to hepatic encephalopathy. Previous studies have indicated the hemodynamic and hormonal mimicry between portal hypertension and hyperthyroidism. Furthermore, medically or surgically induced hypothyroidism has been found to be beneficial in ameliorating hyperdynamic circulation in the portal hypertensive state and in alleviating acute or chronic liver injury in rats. However, the effect of chronic thyroid hormone inhibition on chronic hepatic encephalopathy in cirrhosis remains unknown. METHODS: Liver cirrhosis was induced by bile-duct ligation (BDL) in male Sprague-Dawley rats. Three weeks after BDL, rats were randomized to receive either tap water (control) or 0.04% methimazole in drinking water for 3 weeks. At the end of 6 weeks after BDL, severity of encephalopathy was assessed by the Opto-Varimex animal activity meter and hemodynamic parameters were measured. Blood samples were collected for determination of thyroid stimulating hormone, ammonia and liver biochemistry. RESULTS: The heart rate of the methimazole-treated group was significantly lower than that of the control group (p = 0.015), whereas there were no differences in the mean arterial pressure and portal pressure. The total amount of movements were significantly increased in the methimazole group (p = 0.029). Plasma levels of ammonia, aspartate aminotransferase and alkaline phosphatase were significantly lower (p = 0.01) and thyroid stimulating hormone significantly higher (p = 0.035) in the methimazole group. CONCLUSION: Chronic methimazole treatment alleviates hepatic encephalopathy and liver damage in rats with BDL-induced hepatic cirrhosis.

Lack of detrimental or therapeutic effects of cyclooxygenase inhibition in bile duct-ligated rats with hepatic encephalopathy.

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)-alpha and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), 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-PGF(1alpha), but the motor activity, TNF-alpha 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.

Pyogenic liver abscess associated with large colonic tubulovillous adenoma.

Pyogenic liver abscesses usually occur in association with a variety of diseases. Rarely, liver abscess has been reported as the presenting manifestation of colonic tubulovillous adenoma. We report two cases of pyogenic liver abscess without hepatobiliary disease or other obvious etiologies except that one had a history of diabetes mellitus (DM). The pathogen in the patient with DM was Klebsiella pneumonia (KP). In both of the patients, ileus developed about two to three weeks after the diagnosis of liver abscess. Colonoscopy revealed large polypoid tumors with pathological findings of tubulovillous adenoma in both cases. Two lessons were learned from these two cases: (1) an underlying cause should be aggressively investigated in patients with cryptogenic liver abscess; (2) DM could be one of the etiologies but not necessarily the only cause of KP liver abscess.

Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure.

AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy. Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure. METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of TAA (350 mg/(kg.d) for 3 d. Rats were divided into two groups to receive intraperitoneal injection of indomethacin (5 mg/(kg.d), n = 20) or normal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-alpha (TNF-alpha, an index of liver injury) and 6-keto-PGF(1alpha) (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay. RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs 5%, P<0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S: 438+/-102 vs 841+/-145 counts/30 min, P<0.05). Rats treated with indomethacin had significant higher plasma levels of TNF-alpha (indomethacin vs N/S: 22+/-5 vs 10+/-1 pg/mL, P<0.05) and lower plasma levels of 6-keto-PGF1alpha (P<0.001), but not total bilirubin or creatinine (P>0.05), as compared with rats treated with N/S. CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the aggravation of liver injury. This study suggests that PGI2 may provide a protective role in the development of fulminant hepatic failure.