CD4+Foxp3+ regulatory T cell differentiation mediated by endometrial stromal cell-derived TECK promotes the growth and invasion of endometriotic lesions.

Endometriosis is associated with an abnormal immune response to endometrial cells, which can facilitate the implantation and proliferation of ectopic endometrial tissue. The proportion of CD4(+)Foxp3(+) regulatory T cells (Tregs) is significantly increased in the peritoneal fluid of women with endometriosis. The thymus-expressed chemokine TECK/CCL25 directly promotes the invasiveness of endometrial stromal cells (ESCs). The aim of this study was to investigate the effects of ESC-derived TECK on the crosstalk between Tregs and ESCs in the progress of endometriosis. We determined that the percentage of Tregs and the concentration of TECK increased in the peritoneal fluid with the progression of endometriosis. The supernatant from co-cultured human ESCs and macrophages not only induced Treg differentiation and increased Treg expression of interleukin-10 (IL-10), transforming growth factor-ß (TGF-ß) and CD73 by activating the AKT/STAT3 signaling pathway but also repressed Treg apoptosis by downregulating Fas and FasL expression and enhanced the Treg-mediated suppression of CD4(+)CD25(-) T cells. In addition, in vitro and in vivo trials confirmed that these effects could be inhibited by anti-TECK neutralizing Abs. The secretion of IL-10 and TGF-ß by Tregs increased MMP2 expression and decreased TIMP1 expression and further stimulated the proliferation and invasion of ESCs and the growth of ectopic lesions. These results indicate that TECK derived from ESCs and macrophages upregulates the number and function of Tregs in the ectopic milieu, which contributes to endometriotic immunotolerance and high levels of ESC proliferation and invasion, thereby facilitating the progression of endometriosis.

Outbreak of ertapenem-resistant Enterobacter cloacae urinary tract infections due to a contaminated ureteroscope.

BACKGROUND: Outbreaks of urinary tract infections (UTIs) due to contaminated ureteroscopes have been rarely reported. AIM: To report such an outbreak at a regional teaching hospital in southern Taiwan. METHODS: From October to December 2010, ertapenem-resistant Enterobacter cloacae were identified from urine cultures of 15 patients who had undergone ureteroscopy prior to the infection. Three batches of surveillance cultures were obtained from the environmental objects and healthcare workers related to the procedures. Pulsed-field gel electrophoresis (PFGE) was used for bacterial typing. Antimicrobial susceptibility was assessed by disc diffusion and E-test methods. Polymerase chain reaction and sequencing were used to analyse ß-lactamase genes. FINDINGS: A total of 70 specimens were obtained during the first surveillance operation. One ertapenem-resistant E. cloacae was isolated from a ureteroscope. Although the disinfection protocols for ureteroscopes were revised and implemented, seven additional UTI cases were identified thereafter. The pathogen was identified from two subsequent surveillance cultures and was not eliminated until ethylene oxide sterilization was added to the disinfection protocol. PFGE revealed that all 15 isolates from the patients and the three isolates from the ureteroscope shared a common pattern with minor variance. Most isolates were resistant to gentamicin, levofloxacin, ceftriaxone, ceftazidime, and ertapenem. All isolates were susceptible to amikacin, imipenem, and meropenem. SHV-12 and IMP-8 genes were simultaneously identified in 16 of the 18 isolates. CONCLUSION: The outbreak of ertapenem-resistant E. cloacae was caused by a contaminated ureteroscope and was terminated by the implementation of a revised disinfection protocol for ureteroscopes.

RANKL promotes the growth of decidual stromal cells in an autocrine manner via CCL2/CCR2 interaction in human early pregnancy.

OBJECTIVE: Receptor-activator of NF-κB ligand (TNFSF11, also known as RANKL) and its receptor RANK are essential regulators on bone remodeling, mammary gland development and hormone-associated breast cancer development. However, the expression pattern and role of RANKL/RANK axis in decidual stromal cells (DSCs) are unclear in human early pregnancy. STUDY DESIGN: We analyzed RANKL/RANK expression in DSCs by real-time PCR, immunhistochemistry, enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. Then BrdU cell proliferation assay, flow cytometry assay and ELISA were performed to investigate the effect of recombinant human RANKL and DSCs-derived RANKL on the proliferation, apoptosis, chemokine (C-C motif) ligand 2 (CCL2) secretion, C-C chemokine receptor type 2 (CCR2) and other target proteins expression in DSCs in vitro, respectively. RESULTS: Here we show that DSCs co-express RANKL/RANK. Not only recombinant human (rh) RANKL but also the DSC-secreted RANKL stimulate proliferation and anti-apoptosis, and elevate CCL2 secretion and CCR2 expression of DSCs. Furthermore, the stimulatory effects on the proliferation, anti-apoptosis and the expression of Bcl-2 and Ki67 and inhibitory signaling on Fas ligand (FasL) in DSCs induced by RANKL can be partly reversed by the way of blocking CCL2 and or CCR2. CONCLUSIONS: Our results have revealed that RANKL/RANK signal promotes Bcl-2 and Ki67 and decreases FasL expression, and further as a positive regulator for stimulating the proliferation and growth of DSCs through up-regulating CCL2/CCR2 signal, which finally contributes to the establishment and maintenance of physiological pregnancy.

Effects of caffeinated coffee consumption on intraocular pressure, ocular perfusion pressure, and ocular pulse amplitude: a randomized controlled trial.

PURPOSE: To examine the effects of caffeinated coffee consumption on intraocular pressure (IOP), ocular perfusion pressure (OPP), and ocular pulse amplitude (OPA) in those with or at risk for primary open-angle glaucoma (POAG). METHODS: We conducted a prospective, double-masked, crossover, randomized controlled trial with 106 subjects: 22 with high tension POAG, 18 with normal tension POAG, 20 with ocular hypertension, 21 POAG suspects, and 25 healthy participants. Subjects ingested either 237 ml of caffeinated (182 mg caffeine) or decaffeinated (4 mg caffeine) coffee for the first visit and the alternate beverage for the second visit. Blood pressure (BP) and pascal dynamic contour tonometer measurements of IOP, OPA, and heart rate were measured before and at 60 and 90 min after coffee ingestion per visit. OPP was calculated from BP and IOP measurements. Results were analysed using paired t-tests. Multivariable models assessed determinants of IOP, OPP, and OPA changes. RESULTS: There were no significant differences in baseline IOP, OPP, and OPA between the caffeinated and decaffeinated visits. After caffeinated as compared with decaffeinated coffee ingestion, mean mm Hg changes (± SD) in IOP, OPP, and OPA were as follows: 0.99 (± 1.52, P<0.0001), 1.57 (± 6.40, P=0.0129), and 0.23 (± 0.52, P<0.0001) at 60 min, respectively; and 1.06 (± 1.67, P<0.0001), 1.26 (± 6.23, P=0.0398), and 0.18 (± 0.52, P=0.0006) at 90 min, respectively. Regression analyses revealed sporadic and inconsistent associations with IOP, OPP, and OPA changes. CONCLUSION: Consuming one cup of caffeinated coffee (182 mg caffeine) statistically increases, but likely does not clinically impact, IOP and OPP in those with or at risk for POAG.

Efficacy of enzyme immunoassay for the detection of Helicobacter pylori antigens in frozen stool specimens: local validation.

AIM: To investigate the efficacy of measurement of Helicobacter pylori stool antigen (HpSA) using stored frozen stool specimens, and to assess whether there were factors affecting efficacy in Hong Kong. METHODS: Patients undergoing upper endoscopy at Tuen Mun Hospital were recruited. Stool samples were saved for HpSA testing and questionnaires were completed. Stool samples were frozen immediately upon receipt and stored at -70 degrees C until tested. HpSA results were compared with rapid urease test and histology. RESULTS: One hundred and eighty-one patients were recruited. One hundred and seventy-eight patients were suitable for analysis. Eighty-three were H. pylori positive and 95 were H. pylori negative. The mean duration of storage of the stool samples was 120 days (range, 40-225 days). The sensitivity, specificity and positive and negative predictive values were 84.3%, 97.9%, 97.2% and 88.6%, respectively. In patients with a false negative HpSA test, there was a significant delay in collecting the stool specimen after endoscopy when compared with those with a true positive HpSA test (4.2 vs. 2.3 days; P < 0.05). However, the duration of storage of the specimens was not longer, and consumption of coffee or tea and smoking habits were similar. CONCLUSIONS: HpSA testing showed good sensitivity and specificity, even with frozen stool samples stored for up to 225 days. The efficacy was not affected by coffee, tea or smoking.

Three patients with lead poisoning following use of a Chinese herbal pill.

We report on three patients with lead poisoning following use of the Chinese herbal pill Bao ning dan, prepared by the same traditional Chinese medicine practitioner. The patients had varying degrees of exposure to Bao ning dan and different clinical manifestations. Blood lead concentrations did not correlate with clinical severity. Two patients received chelating therapy and blood lead concentrations subsequently rapidly decreased. One patient was managed conservatively and end-organ complications resolved gradually. With increasing use of traditional Chinese medicines, related adverse reactions are expected to become increasingly common. Practitioners of western medicine should remain alert to this possibility. A comprehensive drug review, including the use of herbal medicines, should form a routine part of medical history taking.

Rapid diagnosis of choledocholithiasis using biochemical tests in patients undergoing laparoscopic cholecystectomy.

BACKGROUND/AIMS: The present study was designed to identify the biochemical tests which could detect the presence of common bile duct stones in patients with symptomatic gallstones, without other invasive investigations. The usefulness of biochemical tests may reduce the necessity of endoscopic retrograde cholangiopancreatography prior to laparoscopic cholecystectomy. METHODOLOGY: 3000 patients with symptomatic laparoscopic cholecystectomy scheduled for laparoscopic cholesystectomy were included in the study. 458 patients (201 men, 257 women; mean age, 57.7 +/- 14.6 yrs) were examined with endoscopic retrograde cholangiopancreatography for suspected common bile duct stones. The serum tests for liver function, including a measurement of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, gamma-glutamyltransferase and albumin were obtained on admission prior to the ultrasonography, and the endoscopic retrograde cholangiopancreatography. RESULTS: The six significant factors, including alkaline phosphatase, direct bilirubin, total bilirubin, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase were identified by the univariate analysis and the multivariate logistic regression analysis which identified alkaline phosphatase and gamma-glutamyltransferase, as the two significant independent factors. A statistical model was developed with a formula of [formula: see text] A curve of receiver operating characteristics was constructed to identify an alkaline phosphatase level greater than 300 U/L or a gamma-glutamyltransferase level greater than 420 mU/mL which would have both higher sensitivity and specificity. CONCLUSIONS: Biochemical tests can be a significant aid to the clinician's decision-making when predicting the presence of common bile duct stones in patients with gallstones.

Palliative percutaneous transhepatic gallbladder drainage of gallbladder empyema before laparoscopic cholecystectomy.

BACKGROUND/AIMS: This study is conducted to evaluate the feasibility of percutaneous transhepatic gallbladder drainage prior to laparoscopic cholecystectomy for the treatment of gallbladder empyema. We also determine the sonographic findings, causative organism, clinical signs and symptoms, laboratory data, associated underlying medical disorders and the complications related to both cholecystostomy and laparoscopic cholecystectomy. METHODOLOGY: One hundred and forty-five cases of gallbladder empyema were included in this study which was composed of 80 males and 65 females, aged 22-94 years with a mean age of 71-years. All patients underwent percutaneous transhepatic gallbladder drainage under ultrasound and fluoroscopic guidance, and laparoscopic cholecystectomy was carried out thereafter. We analyzed the clinical presentations (signs, symptoms, laboratory and ultrasonographic findings, concomitant medical disorders), causative organisms and the complications related to percutaneous cholecystostomy and laparoscopic cholecystectomy. RESULTS: Percutaneous transhepatic gallbladder drainage was performed successfully in all patients within 48 hours after clinical diagnosis of acute cholecystitis. Complications related to percutaneous transhepatic gallbladder drainage were bile leakage after tract dilatation noted in 2 patients (1.4%), and 20 (14%) patients had pain at the puncture site which radiated to the right shoulder during the procedure, but resolved spontaneously within an hour later. On admission, 102 (70%) patients presented as right upper quadrant pain, 39 (27%) as epigastric pain, 90 (62%) as fever, 108 (74%) patients had leukocytosis, and 33 (22.7%) patients were septic. AST and ALT were elevated in 57% and 51% of patients, respectively. Alkaline phosphatase was elevated in 56% of patients, and 34% of those patients had combined common bile duct stones. Gallbladder stones were documented in 135 (93%) patients, while the remaining 10 (7%) cases were acalculous. Five (3.4%) patients had combined gallbladder adenocarcinoma, 7 (4.8%) had liver abscess, while 13 (9%) had biliary pancreatitis. The ultrasonographic findings included gallbladder distension (93%), wall thickening (90%), pericholecystic fluid accumulation (15%), intraluminal sludge or stone (93%) and intraluminal air (13.9%). Bile culture were positive in 83% of the cases and showed gram-negative bacteria in 75%, gram-positive in 30%, anaerobes in 7%, while no growth in the remaining 17% of the cases. The common pathogens were Escherichia coli (57%), Enterococcus (27%), Klebsiella pneumonia (18%), Morganella morganii (7.6%), Pseudomonas aeruginosa (4.1%) and Salmonella (0.7%). The total postoperative complication rate was 17%, which included wound infection, bleeding, subhepatic abscess, cystic duct stump leak, common bile duct injury and pneumonia. Postoperative mortality was 2.6%. Conversion rate to open cholecystectomy was 27%. Clinical conditions improved within 48 hours after cholecystostomy in 93% of patients. Time interval between cholecystostomy and elective cholecystectomy was 2-21 days with a mean of 4 days. Total hospital stay was 5-38 days (mean: 11 days). CONCLUSIONS: Percutaneous transhepatic gallbladder drainage is a safe and effective procedure for the initial management of gallbladder empyema. We highly recommend this preoperative drainage procedure in patient with sepsis, and for those high-risk patients such as old age and with underlying medical illnesses. This procedure can stabilized the patient so that an appropriate therapeutic planning can be achieved.

Video-endoscopic ultrasonography in staging gastric carcinoma.

BACKGROUND/AIMS: Clinical staging of gastric carcinoma is important in designing the strategy of treatment. Early gastric carcinomas can be treated by minimally invasive therapy, whereas advanced gastric carcinomas should be treated by surgery with or without combined chemotherapy. This study was undertaken to evaluate the accuracy and limitations of video type endoscopic ultrasound in preoperative staging of gastric cancer and assessing lymph node metastasis. METHODOLOGY: Seventy-four patients with gastric carcinoma were preoperatively staged using video-endoscopic ultrasonography, performed by the same gastroenterologist. RESULTS: Sixty-three out of the 74 (85%) patients were correctly staged by endoscopic ultrasonography. The diagnostic accuracy rate was 100% for T1, 74% for T2, 87% for T3, and 86% for T4. Overstaging occurred in 11% due to peritumoral inflammation. Understaging occurred in 4% due to microinvasion of carcinomatous tissue or deeper organ invasion. The diagnosis of lymph node metastasis was confirmed in 72% of cases. Sensitivity and specificity was 74% and 86%, respectively. CONCLUSIONS: Endoscopic ultrasonography has a high accuracy rate in staging gastric carcinoma but still has its limitations in evaluating regional lymph node metastasis, despite using a new generation video-endoscopic ultrasonography.

Nonoperative treatment of gastric bezoars using electrohydraulic lithotripsy.

BACKGROUND AND STUDY AIMS: Bezoars are collections of indigestible foreign material that are found within the gastrointestinal tract. Nonoperative approaches such as dietary therapy, enzymatic dissolution, and endoscopic removal have been regarded as the mainstays of therapy. The purpose of this paper is to determine the efficacy of electrohydraulic lithotripsy (EHL) as an alternative form of treatment of gastric bezoars. PATIENTS AND METHODS: Between July 1988 and May 1996, 11 patients with large gastric bezoars, defined as those greater than 5 cm in diameter, received endoscopic-guided fragmentation using electrohydraulic lithotripsy. Nine of our patients had a history of ingestion of "Pho Pu Zi", (Cordia dichotoma Frost. f.), one of orange pitch, and one of ingestion of persimmon. RESULTS: The 11 patients in the study underwent EHL for the treatment of their gastric bezoars, with a 100% success rate, which was defined as the lack of residual bezoar seen on post-procedure barium study or endoscopy done 2 days after the procedure. Patients were followed-up clinically for 30-68 months, with seven of the 11 patients undergoing a barium study with no residual bezoar noted. No procedure-related complications were seen, except for pharyngeal pain which was most probably secondary to the placement of the silicon overtube. CONCLUSIONS: Endoscopically guided electrohydraulic lithotripsy is a safe, highly effective, alternative nonsurgical technique for the treatment of gastric bezoars.

Percutaneous transhepatic transluminal forceps biopsy in obstructive jaundice.

BACKGROUND/AIMS: To evaluate the technical feasibility and sensitivity of percutaneous transluminal forceps biopsy of bile duct diseases. MATERIAL AND METHODS: Seventeen fluoroscopic-guided transluminal forceps biopsies were performed in 16 patients with obstructive jaundice. The technique was performed through an existing percutaneous transhepatic tract. Multiple specimens were obtained after passing the forceps biopsy into a long 9-French sheath and the specimens were fixed with formalin for histopathologic diagnosis. RESULTS: Adequate samples for histological diagnosis was obtained in 12 of 17 procedures (sensitivity, 71%). Pathologic reports included pancreatic head carcinoma n = 2, cholangiocarcinoma n = 3, hepatoma with intrahepatic-bile duct invasion n = 3, common bile duct tumors n = 3 and chronic inflammation n = 1. Minor complications such as pain was noted in three patients while transient hemobilia was seen in two patients. CONCLUSIONS: Percutaneous transhepatic transluminal forceps biopsy is a safe technique which is easy to perform. This can be done through an existing transhepatic biliary tract with a sensitivity rate of 71%.

Increase of resting levels of superoxide anion in the whole blood of patients with decompensated liver cirrhosis.

The aim of this study is to investigate the relationship between the resting level of superoxide anion (O2.) and liver cirrhosis (LC). The resting levels of superoxide anion in the whole blood of healthy controls and patients with compensated or decompensated LC were measured, by an ultra-sensitive chemiluminescence (CL) analyzer and lucigenin amplification. The assay system can be performed in the absence of leukocyte isolation and stimulant administration. The results showed that the blood CL levels of compensated cirrhotic patients (381.0 +/- 201.5 counts/10 s, mean +/- SD, n = 24) were similar to that of healthy controls (467.9 +/- 299.5 counts/10 s, n = 24). However, the blood CL levels of decompensated cirrhotic patients (2083.5 +/- 1462.4 counts/10 s, n = 24) were significantly greater than that of healthy controls and patients with compensated LC (both p < .001, Student's t-test). The correlation analysis revealed that the blood CL levels in cirrhotic patients were significantly correlated with serum concentrations of albumin (r = -0.65, p < .001) and total bilirubin (r = +0.42, p < .005). However, there was no significant correlation between the blood CL levels and serum levels of transaminases (GOT and GPT). These results suggest that blood levels of superoxide of decompensated cirrhotic patients were greater than those of healthy controls or compensated cirrhotic patients. Moreover, the increase of blood levels of superoxide in decompensated cirrhotic patients is related to the impairment of liver function but not to the inflammation.

Helicobacter pylori infection and risk of peptic ulcer among cirrhotic patients.

There is a higher prevalence of peptic ulcer disease in cirrhotic patients than in the general population. Whether Helicobacter pylori is a risk factor for peptic ulcer in cirrhosis remains controversial. The aim of this study was to determine whether there is a significant correlation between H.pylori infection and peptic ulcer in liver cirrhosis. In a cross-sectional study, 49 cirrhotic patients underwent upper gastrointestinal endoscopy and 75 controls (health examinees) without liver disease were also examined by endoscopy. The presence of H. pylori was assessed by culture, histologic findings and rapid urease test of gastric antrum biopsy specimens. Thirty of the 49 (61%) cirrhotic patients had peptic ulcers as compared to 24 of the 75 (32%) controls. The frequency of H. pylori in the antrum in the cirrhotic group was significantly lower than in the control group (39% vs 69%). The presence of H. pylori was more frequent in control patients with gastric (75%) and duodenal ulcers (95%) than nonulcer control patients (59%) whereas the difference between patients with peptic ulcer and nonulcer (40% vs 37%) was not significant in cirrhotic patients. H. pylori was identified in 40% of the cirrhotic patients with duodenal ulcers compared with 95% of controls with duodenal ulcers (p < 0.05). Nevertheless, this difference was not significant among patients with a gastric ulcer between the two groups (40% vs 75%). There was no significant difference in the frequency of H. pylori infection among nonulcer patients between the cirrhotic and control groups (37% vs 59%). In conclusion, we found no evidence to substantiate an etiologic role of H. pylori in the development of a duodenal ulcer in cirrhotic patients.

Sequential changes of bile contents in patients with obstructive jaundice from different etiologies.

BACKGROUND/AIMS: The decreasing of serum concentration of bilirubin and the ability of hepatocytes to excrete various biliary contents after release of obstructive jaundice are good indicators of recovery of liver function. We conducted this study to clarify whether different causes of obstructive jaundice have different effects on the biliary excretion and how they are different when obstruction is released. PATIENTS AND METHODS: Fifteen patients with obstructive jaundice undergoing percutaneous transhepatic catheter drainage or endoscopic nasobiliary drainage were classified into two groups, depending on the cause of obstruction: common bile duct stones (n = 7) and biliary tract tumors (n = 8). All patients in the gallstone group presented with acute cholangitis while only three patients in the tumor group had a positive bacteria culture in bile. Fasting biles were collected on the day of catheter placement and the 2nd, 4th, 6th, 8th, 10th day thereafter. The sequential changes of biliary concentration of bilirubin, phospholipid, cholesterol, bile salts and serum bilirubin were checked and compared between the two groups. RESULTS: The difference in the improvement of jaundice between the stone and tumor group (p > 0.05) were not significant, nor were the excretion of biliary contents after relief of obstruction. The reduction of serum bilirubin paralleled with the increased excretion of biliary bile salts and bilirubin (gamma = -0.51, p < 0.01 and gamma = -0.4, p < 0.05) in tumor group, but not in the stone group. CONCLUSIONS: The decrease of serum bilirubin and the sequential changes of bile contents after relief of obstruction are quite similar in stone and tumor induced obstructive jaundice.

Self-expandable metallic stents in the management of malignant biliary obstruction.

To overcome problems with conventional plastic endoprostheses, a study was conducted to determine the clinical efficacy of self-expandable metallic stents in the palliative treatment of malignant biliary obstruction. From May 1994 to March 1995, 19 self-expandable metallic stents were implanted in 13 consecutive patients with malignant obstructive jaundice due to cholangiocarcinoma (four patients), ampullary carcinoma (six), pancreatic carcinoma (one), and hepatic hilar lymph node metastasis (two). All patients underwent percutaneous transhepatic biliary drainage followed by stent insertion, except for two patients where the T-tube tract was used as access and another with previous placement of a polyethylene internal-external drainage catheter for more than 6 months. When both lobes of the biliary system were to be drained, stents were placed either side by side through punctured, separate hepatic ducts or, using a T configuration, through a single transhepatic tract. Percutaneous transhepatic stent placement was technically successful in all patients. After a mean follow-up of 5.9 months (range, 1-10 mo), 10 of 13 patients were still alive while three had died of nonprocedure-related causes. In 10 patients, total serum bilirubin levels decreased significantly (from 136.8 +/- 157 mumol/L to 34.2 +/- 22.2 mumol/L), while it increased in three patients. Two patients had stent occlusions at 2 and 3 months after stent placement, which required intervention. The overall patency period ranged from 1 to 9 months (mean, 5.1 mo). Our results confirm that the use of metallic stents is effective in the palliative treatment of malignant jaundice.

Endoscopic sphincterotomy prior to laparoscopic cholecystectomy for the treatment of cholelithiasis.

BACKGROUND/AIMS: Laparoscopic cholecystectomy is the standard treatment for symptomatic cholecystolithiasis; however, there is debate on the management of patients with concomitant common bile duct stones. Several options have been suggested; endoscopic sphincterotomy and laparoscopic common bile duct exploration seemed to be the preferred methods at this moment. MATERIALS AND METHODS: We performed endoscopic sphincterotomy prior to laparoscopic cholecystectomy in 51 cases of acute symptomatic cholelithiasis. RESULTS: Endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy procedure-related complication rate was 5.4%, including 1 pancreatitis, 1 cholangitis, and 2 major bleeds. After follow up period of 15-42 months, recurrent stones were found in 2 patients. CONCLUSION: Endoscopic sphincterotomy combined with laparoscopic cholecystectomy is a safe and effective therapy for symptomatic cholecystolithiasis with concomitant choledocholithiasis. Recurrent stones did occur, but further studies are needed to compare the incidence of recurrent stones after endoscopic sphincterotomy and after laparoscopic common bile duct exploration.

Bacteremia in acute pancreatitis of different etiologies.

To evaluate the rationale of using antibiotics in acute pancreatitis and to determine whether the indication for their use depends upon the etiology of the pancreatitis, the records of 202 patients with acute pancreatitis were retrospectively reviewed. The incidence of abnormal body temperature, leukocytosis, bacteremia and the results of biochemistry tests in different etiologies of the disease were investigated. Pancreatitis was found to be alcohol-related (47 patients), gallstone-related (105 patients), idiopathic (26 patients) and miscellaneous (24 patients). On admission, 83 patients had abnormal body temperature and 146 patients showed leukocytosis. Bacteremia occurred in 20 patients. Of these, 15 had gallstone-related pancreatitis, two had pancreatic cancers and one developed bacteremia after endoscopic retrograde cholangio-pancreatography (ERCP). These 18 patients had abnormal biochemistry results (including high serum levels of direct bilirubin, alkaline phosphatase and gamma-glutamyltransferase) and dilated bile ducts on imaging studies, indicating biliary infections. The remaining two patients with bacteremia included one alcoholic patient and one patient with idiopathic pancreatitis. The most commonly involved pathogens were Escherichia coli and Klebsiella pneumoniae. In addition, eight patients (4%) developed secondary pancreatic infections during hospitalization; the blood cultures of seven of these patients were negative on admission. Although fever and leukocytosis are not good predictors of infection in acute pancreatitis our results showed that bacteremia is common in patients whose pancreatitis is related to gallstones, ERCP or pancreatic malignancy with obstructive jaundice. We recommend that antibiotics be used only in this subset of acute pancreatitis patients.

Toxic effects of cholelitholytic solvents on gallbladder and liver. A piglet model study.

We evaluated the toxic effects of four currently used chemolytic solvents--dimethyl sulfoxide (DMSO, 99%), ethyl propionate (EP, 99%), tetrasodium ethyl-dimethyl tetraacetate (4Na-EDTA, 2%, pH 11), and methyl tert-butyl ether (MTBE, purity = 99.5%) in an animal model. Each solvent was tested in nine farm piglets (Landrace), weighing between 20 and 25 kg. A solvent-resistant catheter was inserted transhepatically into the gallbladder (GB) using sonographic guidance 24 hr prior to each experiment. Seventy-five milliliters of each solvent was infused over 3 hr into the gallbladder. The following day, a laparotomy was performed in order to assess for possible damage to the liver, GB, bile ducts (BD), or intestines. The GB and liver were resected and their histology examined. The following pathologic grades were assigned to GB, BD, and liver specimens to describe the tissue damage: normal (0), mild (1), moderate (2), and severe (3). We found that DMSO had the highest score on gallbladder and bile duct injury (49, 3), followed by EP (36, 2), EDTA (14, 1) and MTBE (16, 0), respectively; the difference in gallbladder damage was statistically significant. Very mild hepatocyte damage was present in the DMSO (2) and MTBE (2) groups. The administration of EP and EDTA resulted in no liver injury at all. Piglets within each treatment group suffered from varying degrees of tissue injury. No deaths were attributed to the administered solvents. We concluded that DMSO, EP, EDTA, and MTBE do not have serious local toxic effect on the GB, BD, and intestine; nor do they lead to severe hepatotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Distinct residues of human p53 implicated in binding to DNA, simian virus 40 large T antigen, 53BP1, and 53BP2.

We identified a minimal domain of human p53 required for the transactivation of a p53 response element in Saccharomyces cerevisiae. This domain contains the central region of p53 sufficient for specific DNA binding, which colocalizes with the region responsible for binding simian virus 40 large T antigen, 53BP1, and 53BP2. Thirty amino acid positions, including natural mutational hot spots (R175, R213, R248, R249, and R273), in the minimal DNA-binding domain were mutated by alanine substitution. Alanine substitutions at positions R213, R248, R249, D281, R282, R283, E286, and N288 affected transactivation but allowed binding to at least one of the three interacting proteins; these amino acids may be involved in amino acid-base pair contacts. Surprisingly, alanine substitution at the mutational hot spot R175 did not affect DNA binding, transactivation, or T-antigen binding, although it nearly eliminated binding to 53BP1 and 53BP2. Mutation of H168 significantly affected only T-antigen binding, and mutation of E285 affected only 53BP1 binding. Thus, we implicate specific residues of p53 in different DNA and protein interactions.