***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Gallstone disease is a major health problem throughout the Western world . Approximately 12 % of adults in the United States have gallstones [ 1 , 2 ] . Although most of these persons are asymptomatic [ 3 ] , more than 500 000 cholecystectomies are done yearly for treatment of symptomatic gallstones and associated complications [ 1 ] . Laparoscopic cholecystectomy has made it much easier to manage symptomatic patients , but the annual cost of caring for such patients exceeds $ 5 billion [ 1 ] . Preventing gallstones from forming is therefore an important goal . The development of cholesterol gallstones is associated with certain well-defined risk factors [ 1 , 4 - 6 ] . For most adults , the most important of these factors appear to be obesity and active weight reduction . Several studies have clearly shown that the risk for gallstones increases stepwise with increasing body weight [ 7 - 11 ] . The prevalence of gallstones is two- to threefold greater in persons who weigh as little as 20 % more than their ideal body weight and as much as eightfold greater in patients who exceed their ideal body weight by twofold or more [ 7 - 9 ] . The risk for developing gallstones during active weight reduction is also well accepted [ 9 - 17 ] . Ten percent to 25 % of persons having rapid weight reduction through very-low-calorie dieting develop gallstones [ 12 - 14 ] . In addition , 35 % of patients with morbid obesity develop gallstones as they lose weight after bariatric surgery [ 15 - 18 ] . Ursodeoxycholic acid is a bile salt that reduces cholesterol secretion into bile and improves biliary cholesterol solubility . It is used to dissolve cholesterol gallstones [ 19 - 22 ] . Its properties have led to the hypothesis that it could prevent the formation of cholesterol gallstones in certain high-risk population s. Two previous studies showed that ursodeoxycholic acid could reduce the incidence of gallstone formation in persons participating in a very-low-calorie diet program [ 12 ] and after bariatric surgery [ 18 ] . These preliminary reports inspired two multicenter , r and omized , double-blind , placebo-controlled trials to determine the optimum dose at which ursodeoxycholic acid could prevent gallstone formation in patients having rapid weight reduction . We evaluated approximately 1000 patients participating in a very-low-calorie liquid protein diet program .  A similar study [ 23 ] done in parallel with ours evaluated the effects of ursodeoxycholic acid during weight reduction in more than 300 patients having proximal gastric bypass surgery at 10 surgical weight loss centers . Taken together , these studies clearly show that the prophylactic use of ursodeoxycholic acid is highly effective for the prevention of gallstone formation in patients having rapid weight reduction . Methods Patients We recruited patients from 31 Health Management Re sources -affiliated diet centers throughout the United States that agreed to collaborate in this trial . All patients at these centers were informed of the risk for gallstone formation while dieting and were asked whether they would participate in a study to prevent gallstone formation . To be accepted into this trial , all patients had to 1 ) have a body mass index of 38 kg or more ; 2 ) be between 18 and 70 years of age ; 3 ) be willing to participate in the Health Management Re sources very-low-calorie diet plan for 16 weeks ; and 4 ) have normal serum potassium and calcium levels . Women of childbearing age had to have a negative serum pregnancy test result . Patients were excluded from the study if they had any one the following : 1 ) previous cholecystectomy ; 2 ) gallstones or gallbladder sludge on ultrasonogram ; 3 ) hypersensitivity to bile acids or eggs ; 4 ) a history of hypothyroidism or the Cushing syndrome ; 5 ) an eating disorder or other psychological problem that would interfere with participation in the diet program ; 6 ) use of oral bile salt preparations , aluminum-based antacids , or lithium ; 7 ) long-term use of nonsteroidal anti-inflammatory agents ( including aspirin ) or antihyperlipidemic agents [ including cholestyramine ] within 2 weeks of entering into the trial ; and 8) a total bilirubin level of more than 2.0 mg/dL , a serum creatinine level of more than 2.0 mg/dL , or an alanine aminotransferase level of more than 133 kat/L.  Diuretic therapy had to be discontinued at least 1 day before trial entry . A total of 1004 consecutive patients who met all entry criteria and agreed to participate were enrolled in the trial . The study was approved by the human investigations review committee at each of the participating centers and by the medical review boards of Health Management Re sources , Inc. , and Ciba-Geigy Pharmaceutical Company . Informed consent was obtained from all participants before study entry . Study Design If a patient met all entry criteria and agreed to participate in the study , a baseline ultrasonogram of the gallbladder was obtained and all exclusion criteria were review ed . If gallstones , gallbladder sludge , or both were identified , or if any other exclusion criteria were present , the patient was not entered into the trial . All other patients were entered into the study and r and omly assigned to receive either placebo , 300 mg of ursodeoxycholic acid once daily , 600 mg of ursodeoxycholic acid in two divided doses daily , or 1200 mg of ursodeoxycholic acid in two divided doses daily . Blocks of four patients at each of the 31 centers were used in the r and omization . Treatment groups were blinded using a double-dummy technique . All patients were provided with two coded medication bottles ( one for the morning and one for the evening ) ; each bottle contained either placebo or ursodeoxycholic acid in capsules that were identical in appearance . Patients were instructed to take two pills from the morning bottle and two pills from the evening bottle daily . Thus , each patient took two capsules twice daily . Each patient began taking coded medication on the first day that he or she began the Health Management Re sources diet plan and continued to take it throughout the entire 16-week program . The Health Management Re sources diet was a 520-kcal/d liquid protein diet containing 50 g of protein , 79 g of carbohydrate , and 1 to 3 g of fat ( depending on the particular preparation selected ) . All patients consumed this diet 3 to 5 times daily for 16 weeks and were instructed not to consume any other food . Supplements providing 100 % to 150 % of the U.S. recommended daily allowance of vitamins and minerals were supplied for each patient . Consumption of noncaloric fluids ( water and diet or club sodas ) was not limited . Each patient was evaluated biweekly throughout the study . At each visit , body weight and all adverse experiences that had occurred since the previous visit were recorded . Patients were instructed to return all medication bottles and unused medications to their study center . Compliance with study medication was assessed by pill count . Gallbladder ultrasonography was repeated after 8 weeks of dieting and after 16 weeks of dieting or termination from the trial , or both . Gallstones and gallbladder sludge were defined using st and ard and well-accepted criteria [ 24 ] . Radiologists from each of the 31 participating centers met and agreed to these criteria before the start of the study . Although the radiologists were aware that the patients were participants in this study , they were blinded to the particular group to which each patient had been assigned . The reading of the radiologist at each site was considered final , and these findings were not review ed by a single central radiologist . If a patient was found to have developed one or more gallstones , his or her participation in the trial was complete . No further weight loss data were collected from these patients as part of the trial . Gallbladder sludge was not considered a primary end point . Patients who developed sludge were informed of this and were continued in the trial . Bile Analysis Thirty-two patients from a single Health Management Re sources center ( Austin Diagnostic Center , Austin , Texas ) volunteered to participate in bile analysis . Each of these patients had endoscopy to obtain  bile  for analysis before starting the diet and at the completion of the trial . All patients had routine upper endoscopy while under conscious sedation ( midazolam , 2 mg to 4 mg ) in the morning , after an overnight fast . The tip of the endoscope was advanced into the second portion of the duodenum , and the ampulla of Vater was visualized . An intravenous dose of sincalide ( Kinevac , 0.02 to 0.06 g/kg ) was then administered to stimulate gallbladder contraction . As bile entered the duodenum , it was aspirated through the suction port of the endoscope and collected . Bile sample s were immediately centrifuged at 25 000 g for 30 minutes , and a sample of the sediment was examined for cholesterol crystals with a polarizing microscope ( magnification , 400 ) . The supernatant was frozen for later analysis by the primary investigator . All bile sample s were thawed and analyzed as a single batch . Total phospholipid levels were determined by the method of Bartlett [ 25 ] . Cholesterol was determined in whole bile after appropriate dilution with an assay kit ( Sigma Chemical Co. , St. Louis , Missouri ) . The bile salt composition of each bile sample was determined using reverse-phase , high-performance liquid chromatography in a Waters model 600 system ( Waters Chromatography , Milford , Massachusetts ) as described previously [ 26 ] . The percentage of total bile acids that were conjugates of ursodeoxycholic acid ( tauro-plus glyco- ) was assessed . The cholesterol saturation index of each bile sample was calculated from tables developed by Carey [ 27 ] using the computer program of Kuroki and colleagues [ 28 ] . Four patients did not have enough bile collected to allow paired analysis of cholesterol saturation and assessment of the percentage of ursodeoxycholic acid . Statistical Analysis The Ciba-Geigy Pharmaceutical Company was responsible for overseeing data collection and data analysis . BACKGROUND Hyperinsulinaemia has been associated with many common diseases in developed countries , such as ischaemic heart disease and colon cancer . Gall stones are also very prevalent in these countries but little is known about the association between insulin and gall stones . AIMS To study the relationships between insulin and the incidence of gall stones in a sample of the general population . SUBJECTS AND METHODS Between May 1985 and June 1986 , systematic sampling from the electoral register of Castellana , a small town in southern Italy , yielded 2472 subjects who had their gall bladder checked for gall stones by ultrasonography . Between May 1992 and June 1993 , 1962 of the 2235 subjects without gall stones at the first examination agreed to a further ultrasound examination . A total of 101 subjects with newly diagnosed gall stones and 303 r and omly chosen controls entered the study . Serum insulin  was determined by radioimmunoassay , and concentrations of cholesterol , cholesterol high density lipoprotein ( HDL ) , glucose , and triglycerides by st and ard enzymatic colorimetric methods . Unconditional multiple logistic regression was used to study the association between  insulin  and gall stones , controlling for the most common confounding factors . RESULTS In individuals with no clinical diagnosis of diabetes and serum glucose < 7 mmol/l ,  insulin  was associated with gall stones . This association persisted even after controlling for sex , age , body mass index , and serum glucose . The risk of gall stones in the highest quintile of serum insulin was 2.66 ( 95 % confidence interval 1.04 - 6.72 ; chi(2 ) test for trend , p=0.03 ) . The association of  insulin with gall stones persisted when total and HDL cholesterol were entered in the logistic regression models , and only slightly decreased when serum triglycerides were included in the model . CONCLUSIONS The results of the study indicate that hyperinsulinaemia may play an important role in the aetiology of gall stones even in individuals without diabetes and with normal serum glucose levels It has been reported that intake of ( n-3 ) polyunsaturated fatty acids ( PUFA ) reduces the risk of coronary heart disease and decreases biliary cholesterol saturation in the bile of gallstone patients . We investigated the effect of n-3 PUFA on cholesterol saturation index ( CSI ) and nucleation time ( NT ) in obese subjects who were losing weight . This was a double-blind , placebo-controlled clinical trial . Obese women ( n = 35 ) with a body mass index ( BMI ) > or = 30 kg/m(2 ) , with no prior history of gallstones or cholecystectomy by ultrasound were first studied to ensure absence of stones or biliary sludge . The women were then assigned to a hypocaloric regimen [ 5.02 MJ ( 1200 kcal)/d ] and to receive 1200 mg/d of ursodeoxycholic acid ( UDCA ) , 11.3 g/d of ( n-3 ) PUFA or a placebo for 6 wk . BMI , CSI and NT were recorded at baseline and at the end of the experimental period . BMI decreased 5.75 + /- 2.7%/mo ( range , 1.5 - 12.42%/mo ) during the experiment . The CSI did not change in any of the groups . Cholesterol NT decreased significantly in the UDCA and placebo groups , but not in the ( n-3 ) PUFA group . None of 
    Output:
    
On the basis of a meta- analysis of r and omized controlled trials , during weight loss , UDCA and /or higher dietary fat content appear to prevent formation of gallstones