Multiple Cholesterol Gallstones Research Articles

Index of Suspicion * Case 1: Abdominal Pain, Vomiting, and Weakness in an Obese Adolescent * Case 2: Bowlegs in a Toddler * Case 3: Cyclical Abdominal Pain and Urinary Symptoms in a Teenage Girl

A 15-year-old girl is hospitalized with right upper quadrant abdominal pain, vomiting, and weakness of 3 days' duration. She has a history of hyperlipidemia, polycystic ovary syndrome (PCOS), metabolic syndrome, and left ovarian cystadenectomy. She has been taking oral contraceptives (OCPs) and metformin for the past 2 years and started spironolactone 8 weeks ago. She experienced menarche at age 12 years and had one menstrual cycle for the whole first year. There is no history of dysmenorrhea or menorrhagia. Her family history is positive for type 2 diabetes mellitus (DM), obesity, and gallstones. On physical examination, her body mass index (BMI) is 28.0 kg/m2 (95th percentile), and she is in mild distress due to pain. Her blood pressure is 128/76 mm Hg (90th percentile for age and height); the remainder of her vital signs are normal. She has acanthosis nigricans and hirsutism. She is at Sexual Maturity Rating 5. She has mild tenderness in the right upper abdominal quadrant, but there is no organomegaly or rigidity. The rest of the physical findings are normal. Laboratory results reveal serum amylase of 660 units/L, lipase of 263 units/L, AST of 868 units/L, ALT of 1,573 units/L, cholesterol of 216 mg/dL (5.6 mmol/L), triglycerides of 181 mg/dL (2.0 mmol/L), high-density lipoprotein (HDL) cholesterol of 33 mg/dL (0.9 mmol/L), and glucose ranging from 120 to 148 mg/dL (6.7 to 8.2 mmol/L). Ultrasonography shows multiple cholesterol gallstones and a thickened gall bladder. Additional investigation reveals the diagnosis. A healthy 2-year-old girl presents to the clinic for evaluation of bowlegs. She was born at term and had a birthweight of 6 lb 11 oz. Her development has been normal, and she eats a regular diet. However, the bowing of her legs has increased progressively since she started walking at 1 year of age. There is …

Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells

Phospholipase A(2) IIA (PLA(2)IIA), which plays a crucial role in arachidonic acid metabolism and in inflammation, is upregulated under various pathological conditions, including in the gallbladder and gallbladder bile from patients with multiple cholesterol gallstones, in the liver and kidney of rats with cirrhosis, as well as in the colonic tissue of animals treated with a chemical carcinogen. The administration of ursodeoxycholic acid (UDCA) partially attenuated the PLA(2)IIA expression level in these different models. The aim of this study was to investigate the modulatory effect of UDCA on the PLA(2)IIA expression level at the cellular level. The HepG2 cells were selected to investigate the direct inhibitory effect of UDCA on PLA(2)IIA expression level. The proinflammatory cytokines (interleukin-6 and tumor necrosis factor alpha) -induced PLA(2)IIA expression in HepG2 cells was partially inhibited by the presence of UDCA in a dose-dependent fashion. The effect of UDCA on proinflammatory cytokines-induced PLA(2)IIA expression occurred at the transcriptional level. In addition, among the bile acids tested, this inhibitory effect was UDCA-specific. In conclusion, this study supports the possible alteration of arachidonic acid metabolism and PLA(2)IIA expression level, in particular, as the protective action of UDCA in patients with chronic liver disease.

Analysis Algerian’s gallstones with infrared spectrum and methods of prevention and treatment for cholelithiasis in algeria

To analyze the type of Algerian’s gallstones and put forward relative measures of prevention and treatment, The NICOLET 170SX FT-IR spectrometer was used to measure the infra-red spectrum and analyze the feature of spectrum of Algerian’s gallstones. The results shown that Algerian have cholesterol gallstones. Reasons to form Algerian’s multiple cholesterol gallstones were investigated. We have put forward five suggestions to prevent and treat cholelithiasis.

Successful direct dissolution therapy with MTBE following percutaneous gallbladder drainage in an elderly gallstone patient with large multiple cholesterol gallstones complicated with acute cholecystitis

Successful direct dissolution therapy with MTBE following percutaneous gallbladder drainage in an elderly gallstone patient with large multiple cholesterol gallstones complicated with acute cholecystitis

Single and multiple cholesterol gallstones and the influence of bacteria

Single and multiple cholesterol gallstones constitute at least 80% of the gallstone population observed at cholecystectomy in Western countries. While supersaturation of bile with cholesterol is necessary for gallstone growth, the kinetic determinant of crystal nucleation is perhaps the critical factor leading to the incidence of gallstones. Nucleation involves aggregation of nidus-forming materials like pigment precipitates and mucus proteins. In combination with cholesterol precipitates and crystal formation, gallstone propagation is enhanced. Bacterial species may augment the process of nucleation and gallstone growth by contributing specific enzyme activities resulting in the formation of insoluble precipitates in bile, or by acting as a nidus upon which the deposition of cholesterol crystals may initiate gallstone formation. The utilization of Raman microscopic techniques permits detailed mapping of the distribution of the gallstone components leading to identification and characterization of the site of nucleation. This, when coupled to molecular genetic tools such as PCR DNA amplification, would permit elucidation of the role of bacteria in vivo gallstone propagation mechanisms.

Cholesterol crystallization in human gallbladder bile: relation to gallstone number, bile composition, and apolipoprotein E4 isoform.

Patients with multiple cholesterol gallstones are at increased risk of recurrence after nonsurgical therapy, possibly because of fast biliary cholesterol crystallization. Serum apolipoprotein E4 (apo E4) is a risk factor for primary cholesterol gallstone formation as well as recurrence. We examined potential effects of stone number and apolipoprotein E genotype on crystallization and on various crystallization-influencing factors in gallbladder biles of 36 cholesterol stone patients (25 multiple stones: 10 carrying the epsilon4 allele). Biliary cholesterol saturation, bile salt composition or concentrations of total protein, immunoglobulin (Ig)A, IgG, alpha1-acid glycoprotein, haptoglobin, or mucin--all crystallization promoters--did not differ between multiple and solitary stone patients, apparently not explaining different speed of crystallization (crystal observation time 3.5 +/- 0.6 days vs. 12.7 +/- 2.4 days, respectively; P = .0003). In contrast, biliary aminopeptidase-N activities (2,607 +/- 592 mU/mL vs. 947 +/- 185 mU/mL; P = .04) were higher and IgM levels (179 +/- 39 vs. 65 +/- 8 mg/L; P = .09) tended to be higher in the case of multiple stones. Although patients carrying the epsilon4 allele had similar stone numbers and crystallization as patients without the epsilon4 allele, their cholesterol saturation index (CSI) was lower (1.08 +/- 0.09 vs. 1.54 +/- 0.13; P = .01), whereas total protein and bile salt concentrations tended to be higher with preferential taurine-conjugation. In conclusion, fast cholesterol crystallization is associated with multiple stones but not with apolipoprotein E4. Whereas fast crystallization may contribute to high recurrence rates after nonsurgical therapy in case of multiple gallstones, the mechanism for increased risk of gallstone formation in patients carrying the epsilon4 allele remains unknown.

α 1-Acid glycoprotein is increased and associated with rapid nucleation in gallbladder bile with multiple cholesterol gallstone but not with solitary cholesterol or pigment gallstones

• ~-ACID GLYCOPROTEIN IS INCREASED AND ASSOCIATED WITH RAPID NUCLEATION IN GALLBLADDER BILE WITH MULTIPLE CHOLESTEROL GALLSTONES BUT NOT WITH SOLITARY CHOLESTEROL OR PIGMENT GALLSTONES. Masato Abel, Naomi Tanaka, Shinji Tomita, Junichi Shoda, Takashi Yamaguchi*, ~ t s u z a k i , Toshiaki Osuga. Dept. of Gastroenterology, Institute of Chical Medicine, University of Tsukuba, and *Dept. of Gastroenterology, National Mito Hospital, Ibaraki, JAPAN. We have reported that the biliary a,-acid glycoprotein(AAG) promotes cholesterol(eho)-crystallization in vitro(Gastroenterology 106:231,1994) and that its level is elevated in gallbladder bile(GBE) with multiple(m) cho-gallstone (GS)(Hepatology 16:154A,1992). It is not known whether biliary AAG level is altered in GBB with other types of GS. AIM: To determine the precise role of biliary AAG in GS pathogenesis, AAG levels in GBB with different types of GS and their association with rapid NT were studied in comparison with control biles. METHODS: GBB was obtained during operation from 20 controls without GS and from 48 GS patients. GS were classified into 33 choI-GS(13 solitary(s), 20 m) and 15 pig-GS(10 s, 5 m) based on visual inspection and chemical analysis. AAG in GBB was measured by specific ELISA. RESULTS: As shown in the Table, CSI was higher and NT was shorter in GBB with cho-GS than in GBB with pig-GS or control biles. NT of m-cho-GS was shorter than that of s-cho-GS, but CSI was not different in both groups. Both AAG and AAG/total protein were significantly higher in GBB with m-cho-GS than in GBB with s-cho-GS, pig-GS or in control biles. Both AAG and AAG/total protein were significantly correlated with NT(r=-0.49; P 100 Ixg/ml, all of which were associated with very rapid NT, whereas only 1 of 13 m-choI-GS, none of 15 pig-GS, 1 of 20 controls showed AAG>100 pg/ml(p 100 p.g/ml for m-chol GS were 0.50, and 0.96, respectively. Table *p <january 1989), previous history of jaundice, asoites, encephalopathy and serum sodium. Only date of transplantation and serum sodium were kept in the final multivariate model. Our study shows that besides improvement of technical skill and peroperative management, only sodium influence 30 days mortality after liver transplantation.

Primary and secondary prevention of gallstone disease: Implications for patient management and research priorities

Primary prevention is defined as the prevention of gallstone formation; secondary prevention is defined as the prevention of clinical manifestations of gallstones--symptoms or more severe complications. For primary prevention, general "wellness" measures can be recommended from a theoretic standpoint. These include elimination of obesity (to decrease excessive cholesterol biosynthesis or mobilization of tissue cholesterol during rapid weight loss); a high-fiber, high-calcium diet (to diminish input of deoxycholic acid); ingestion of meals at regular intervals (to diminish gallbladder storage and interruption of the enterohepatic circulation of bile acids); and vigorous exercise (to permit frequent meals without excessive caloric intake). In addition, based on animal studies, intake of low saturated fatty acids may diminish the nucleation of supersaturated bile. Secondary prevention is recommended only when gallstones become symptomatic because of the benign natural history of asymptomatic gallstones, the intrinsic limitations of medical therapy, and the absence of predictors that would enable selection of asymptomatic patients at high risk for becoming symptomatic. Secondary prevention involves nonsurgical approaches (dissolution with ursodiol, extracorporeal shock-wave lithotripsy plus adjuvant bile acids, and, rarely, contact dissolution with organic solvents). For patients with symptomatic gallstones, nonsurgical therapy will be used by those patients who cannot or will not have surgery, as well as those patients who wish to explore a trial of nonsurgical therapy before having surgery. Because of the intrinsic limitations of nonsurgical therapy in comparison to the efficacy and safety of surgery, most patients will undergo surgery. Future research priorities include elucidation of factors responsible for: (1) bile that is supersaturated in cholesterol; (2) elevated biliary deoxycholic acid levels in patients with cholesterol gallstones; (3) rapid nucleation in patients with multiple cholesterol gallstones; (4) precipitation of calcium bilirubinate; and (5) impaired gallbladder motility in gallbladder stone disease.

Cholesterol nucleation time in gallbladder bile of patients with solitary or multiple cholesterol gallstones.

Patients with multiple cholesterol gallbladder stones have been found to be at a higher risk for the recurrence of gallstones after successful nonsurgical treatment than those with a solitary stone. Cholesterol gallstone recurrence, like primary gallstone formation, probably involves a triple defect with supersaturation, abnormally rapid nucleation of cholesterol in bile and altered gallbladder motor function. We investigated whether the increased recurrence rate of patients with multiple stones might be caused by more rapid nucleation. Therefore the time required for cholesterol monohydrate crystals to appear in ultracentrifuged bile of patients with solitary (n = 71) or multiple (n = 42) cholesterol gallstones was determined. The cholesterol nucleation time was significantly (p less than 0.01) longer in the bile from patients with solitary stones (less than 1 to 16 days, median = 2.0 days) than in the bile from patients with multiple stones (less than 1 to 8 days, median = 1.0 days). Moreover, 15 of 71 (21.1%) patients with solitary cholesterol stones but only 1 of 42 (2.4%) patients with multiple cholesterol stones showed a normal (greater than 4 days) nucleation time. However, no difference in the cholesterol saturation index was found between the bile samples from patients with solitary stones and the bile samples from patients with multiple stones (1.55 +/- 0.65 vs. 1.54 +/- 0.59, mean +/- S.D., respectively). The more rapid cholesterol nucleation in gallbladder bile may, therefore, be the major risk factor causing the higher percentage of stone recurrence in patients with multiple cholesterol stones as compared with patients with solitary cholesterol stones.

Isolation of a potent cholesterol nucleation-promoting activity from human gallbladder bile: Role in the pathogenesis of gallstone disease

Gallbladder bile contains nucleation-promoting activity that binds to concanavalin A. The activity was found in gallbladder bile from cholesterol gallstone patients but also in gallbladder bile from patients without stones and patients with pigment stones. Bile from patients with multiple cholesterol gallstones contained high concanavalin A-binding nucleation-promoting activity. The activity was much lower in bile samples from pigment stone patients, patients without stones and patients with a solitary cholesterol stone. Serum contained very little activity and no concanavalin A-binding nucleation-promoting activity could be demonstrated in gallbladder mucosa. This suggests that concanavalin A-binding nucleation promoter is produced in the liver or bile duct epithelium. The activity was fully resistant to digestion with pronase but was heat labile and could be destroyed by prolonged incubation with a mixed glycosidase preparation indicating that sugar residues are important for this activity. On a Superose 12 gel permeation column, promoting activity eluted in two major peaks at apparent molecular weights of 150 +/- 30 kD (n = 5) and less than 5 kD respectively. The mobility on the column was not influenced by pronase digestion. The factor with the higher molecular weight could be isolated further by polyacrylamide gel electrophoresis under nondenaturing conditions. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the apparent molecular weight of the glycoprotein was 130 kD. In conclusion, gallbladder bile contains nucleation-promoting activity that binds to concanavalin A. The activity is increased in bile from patients with multiple cholesterol gallstones and could therefore play an important role in the pathogenesis of gallstone disease.

Comparison of cholesterol nucleation time in gallbladder bile of patients with solitary or multiple cholesterol gallstones

Comparison of cholesterol nucleation time in gallbladder bile of patients with solitary or multiple cholesterol gallstones