Changes in gallbladder bile composition following gallstone formation and weight reduction.

Changes in gallbladder bile composition that occurred in patients who developed gallstones during weight reduction were evaluated. Bile was sampled directly from the gallbladder in 11 morbidly obese patients with no gallstones at the time of gastric bypass surgery and after gallstones had formed at cholecystectomy. Bile salt concentration ([BS]) increased significantly from a mean of 82.7-157.7 mmol/L (P less than 0.05). The concentration of cholesterol in gallbladder bile increased slightly and cholesterol saturation declined slightly with weight reduction and gallstone formation. Gallbladder mucin concentration increased 18-fold from a mean of 62 to 1110 micrograms/mL (P less than 0.001). Both free [Ca2+] and total calcium [Ca] increased 40% from mean values of 1.12 and 5.05 mmol/L at gastric bypass to 1.86 and 8.60 mmol/L after gallstone formation (P less than 0.05). The increase in [Ca2+] observed after gallstone formation was much greater than anticipated from changes in [BS] alone. This excess [Ca2+] in gallbladder bile increased curvilinearly with increasing mucin concentration. These results show that both gallbladder mucin and [Ca2+] increase with gallstone formation in humans and that mucin may modulate [Ca2+] in gallbladder bile.     

Bile concentration is a key factor for nucleation of cholesterol crystals and cholesterol saturation index in gallbladder bile of gallstone patients

We investigated whether bile concentration influenced cholesterol saturation index or nucleation time of cholesterol monohydrate crystals in a large number of gallbladder bile samples. Pigment stone patients never had cholesterol crystals in their fresh biles, and nucleation time was always longer than 20 days. Of the cholesterol stone patients 79% had cholesterol crystals in their fresh biles. Long nucleation times were generally found in cholesterol stone patients with dilute biles despite a high cholesterol saturation index. Nucleation time was usually short if bile was well concentrated despite a relatively low saturation index. Serial in vitro dilution of concentrated biles from cholesterol gallstone patients resulted in progressively prolonged nucleation times. Patients with solitary cholesterol stones had longer nucleation times than patients with multiple cholesterol stones. This study indicates that bile concentration is an important factor for nucleation time and cholesterol saturation index. Moreover, solitary and multiple cholesterol stones may have a different pathogenesis.     

Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility

Ceftriaxone, a semisynthetic third-generation cephalosporin, has recently been associated with biliary sludge formation. Analysis of the biliary concretions induced by this agent shows a calcium salt of ceftriaxone. The present in vitro studies were undertaken to provide insight into the pathogenesis of ceftriaxone-associated biliary sludge formation by evaluating possible interactions that may exist between calcium, bile salts, and ceftriaxone. Ceftriaxone possessed high calcium-binding affinity. The formation constant for the calcium ceftriaxone salt at 37 degrees C was about 157.3 L/mol; stoichiometry of the salt was 1:1, i.e., calcium ceftriaxone. The calcium-binding property of ceftriaxone was observed to be additive to that of taurocholate in mixed taurocholate-ceftriaxone solutions. Although the solubility product constant for calcium ceftriaxone was only 1.62 x 10(-6) mol/L2, marked metastability was observed; neither visible nor microscopic precipitates developed until the [Ca2+] x [ceftriaxone] ion product exceeded the solubility product constant by a factor of 10.4. Metastability of the calcium ceftriaxone salt was also observed in human gallbladder bile in vitro. Estimates of human biliary calcium ceftriaxone solubility in vivo were than calculated from previously-reported values for biliary [Ca2+], [ceftriaxone], and from the solubility product constant as defined in this study. Calculated saturation indices for calcium-ceftriaxone in human bile generally increased (corresponding to a decrease in solubility) with increasing ceftriaxone dose. At doses less than or equal to 1 g, saturation index was well within the metastable range of this calcium-salt. However, at doses greater than or equal to 2 g, the saturation index surpassed the metastable limit. Under these conditions, precipitation of ceftriaxone could occur. It was concluded that the development of ceftriaxone-induced biliary sludge is a solubility problem that occurs in patients receiving high-dose treatment (greater than or equal to 2 g). This study proposes that the risk of developing ceftriaxone-associated biliary "pseudolithiasis" increases with increasing ceftriaxone dose and in patients with impaired gallbladder emptying.     

Cholesterol and pigment gallstone disease: comparison of the reliability of three bile tests for differentiation between the two stone types

Gallbladder biles and stones were obtained at 116 cholecystectomies for symptomatic gallstone disease. All 33 patients younger than 50 years had cholesterol stones, whereas 40% of the older patients had pigment stones. We compared the reliability of three different bile tests for the differentiation between cholesterol and pigment stone patients. Whereas both the presence of cholesterol monohydrate crystals in fresh gallbladder bile and a nucleation time less than or equal to 20 days in ultrafiltered gallbladder bile had a specificity of 100% for cholesterol gallstone disease, biliary supersaturation with cholesterol (cholesterol saturation index greater than 1.0) had a low specificity. The sensitivity of nucleation time less than or equal to 20 days for cholesterol gallstone disease was 78% in concentrated gallbladder biles (biliary total lipid concentration greater than or equal to 5 g/dl) but only 21% in dilute biles (biliary total lipid concentration less than 5 g/dl). In contrast, examination for the presence of cholesterol crystals in fresh bile was reasonably sensitive both in concentrated and dilute gallbladder biles (sensitivity, 84% and 72%, respectively). In addition, duodenal bile obtained from 16 patients (10 cholesterol, 6 pigment) before cholecystectomy showed cholesterol crystals in 7 of the cholesterol but in none of the pigment stone patients. We conclude that examination of fresh bile for cholesterol crystals is a specific and reasonably sensitive test for cholesterol gallstone disease.     

Evidence for H+ secretion by the in vivo canine gallbladder

In humans and most other species, a decline in pH of gallbladder contents occurs during the concentration of bile. Recent in vitro studies in rabbit, guinea pig, and Necturus gallbladders have strongly suggested mucosal H+ secretion during sodium reabsorption, presumably representing a Na+/H+ exchange. The present in vivo studies are the first attempt to determine whether H+ secretion by the gallbladder can be demonstrated in the living animal. Gallbladder bile was obtained from 27 anesthetized dogs after 12-24-h fasts; 12 samples of common duct bile were also obtained in 3 dogs during variable taurocholate infusion. In common duct bile, observed ranges were as follows: pH, 7.37-7.85; CO2 partial pressure (PCO2), 21-32 mmHg; total CO2 concentration ([TCO2]), 16.4-41.4 mM; total bile salt concentration ([TBS]), 16-93 mM; and [Na], 153-192 mM. In gallbladder bile, respective ranges were as follows: pH, 5.72-7.29; PCO2, 36-101 mmHg; [TCO2], 1.21-15.5 mM; [TBS], 150-305 mM; and [Na], 199-266 mM. In all samples [Na] was linearly related to [TBS]. Carbon dioxide partial pressure increased from a mean of 27.3 mmHg in common duct bile to greater than 100 mmHg in gallbladder bile at [TBS] = 180 mM, then declined to approximately 36 mmHg as [TBS] increased to greater than 300 mM. Peak PCO2 occurred at pH approximately 6.4-6.6, then declined as pH decreased to approximately 5.7. Bile to plasma PCO2 ratios increased from a mean of 1.08 in common duct samples to greater than 2.0 in gallbladder samples at pH approximately 6.3, then declined to approximately 1.0 in fully concentrated bile. If the high PCO2 values in bile were solely due to tissue CO2 production, a sustained increase in PCO2 throughout Na+ reabsorption might be expected. The results strongly suggest H+ secretion (HCO3- neutralization), as peak PCO2 occurred when [TBS] was only about 180 mM, long before sodium absorption was complete. It is hypothesized that H+ secretion may have important favorable effects on calcium lithogenicity, reducing the likelihood of the formation of CaCO3- containing gallstones.     

Decreased protein concentration and improved metastability of bile induced by ursodeoxycholate

Previous studies demonstrated that higher biliary protein is associated with reduced metastability of bile. This study attempted to examine the induced effect of ursodeoxycholate on metastability of bile by measuring the nucleation time and biliary protein in cholesterol gallstone patients. Thirty-seven patients with functioning gallbladders were studied 10 control patients without gallstones and 27 with cholesterol gallstones. Ten of 27 cholesterol gallstone patients were treated with ursodeoxycholate (600 mg/ day) prior to surgery. Twelve of 17 untreated gallstone patients had cholesterol crystals in gallbladder bile while cholesterol crystals were absent in the ursodeoxycholate-treated gallstone patients and in the controls. Total protein concentration and cholesterol saturation index were significantly greater in the untreated gallstone patients with crystals than in those without crystals in bile. The treatment with ursodeoxycholate significantly decreased biliary protein concentration and cholesterol saturation index associated with the prolonged nucleation time. Cholesterol nucleation time correlated with biliary total protein concentration and cholesterol saturation index but not with total lipid concentration. It is concluded from the present study that ursodeoxycholate decreases biliary protein thereby partly increasing metastability of gallbladder bile.     

Decreased protein concentration and improved metastability of bile induced by ursodeoxycholate.

Previous studies demonstrated that higher biliary protein is associated with reduced metastability of bile. This study attempted to examine the induced effect of ursodeoxycholate on metastability of bile by measuring the nucleation time and biliary protein in cholesterol gallstone patients. Thirty-seven patients with functioning gallbladders were studied 10 control patients without gallstones and 27 with cholesterol gallstones. Ten of 27 cholesterol gallstone patients were treated with ursodeoxycholate (600 mg/day) prior to surgery. Twelve of 17 untreated gallstone patients had cholesterol crystals in gallbladder bile while cholesterol crystals were absent in the ursodeoxycholate-treated gallstone patients and in the controls. Total protein concentration and cholesterol saturation index were significantly greater in the untreated gallstone patients with crystals than in those without crystals in bile. The treatment with ursodeoxycholate significantly decreased biliary protein concentration and cholesterol saturation index associated with the prolonged nucleation time. Cholesterol nucleation time correlated with biliary total protein concentration and cholesterol saturation index but not with total lipid concentration. It is concluded from the present study that ursodeoxycholate decreases biliary protein thereby partly increasing metastability of gallbladder bile.     

Impaired biliary cholesterol secretion and decreased gallstone formation in apolipoprotein E-deficient mice fed a high-cholesterol diet

BACKGROUND & AIMS: Because apolipoprotein E (apoE) is a key cholesterol transport molecule involved in the hepatic uptake of chylomicron cholesterol, it may play a critical role in controlling bile cholesterol elimination and cholesterol gallstone formation induced by dietary cholesterol. To test this hypothesis, we studied biliary lipid secretion and gallstone formation in apoE-deficient mice fed cholesterol-rich diets. METHODS: Bile lipid outputs and gallstone sequence events were analyzed in apoE-deficient mice fed a high-cholesterol diet or a lithogenic diet compared with control animals. RESULTS: A high-cholesterol diet increased biliary cholesterol secretion and gallbladder bile cholesterol concentration in wild-type mice; the increase in bile cholesterol secretion was significantly attenuated in apoE-deficient mice. ApoE knockout mice fed a high-cholesterol lithogenic diet had a markedly lower frequency of gallbladder bile cholesterol crystal and gallstone formation than wild-type mice, which was most likely a result of the decreased cholesterol saturation index found in gallbladder bile of apoE-deficient mice. CONCLUSIONS: These results show that apoE expression is an important factor for regulating both biliary secretion of diet-derived cholesterol as well as diet-induced cholesterol gallstone formation in mice.     

The composition of hepatic and gallbladder bile in patients with gallstones

Bile specimens were obtained from 17 patients with gallstones and 21 patients with duodenal ulcer. The specimens were obtained from the former by needle aspiration of the gallbladder and common bile duct at operation and from the latter by duodenal intubation. The concentrations of bile salt, phospholipid, and cholesterol were measured. Gallbladder bile from gallstone patients contained significantly more cholesterol than did ;duodenal' bile from duodenal ulcer patients. Hepatic bile from gallstone patients contained significantly more cholesterol than did gallbladder bile from the same patients. When the data were plotted on triangular coordinates the relative composition lay within the zone of cholesterol solubility in all 21 ulcer patients. The relative composition of hepatic bile lay outside the zone of cholesterol solubility in five gallstone patients, at the limits of cholesterol solubility in a further three, and within the micellar zone in the remaining nine patients. This suggests that supersaturation of hepatic bile with cholesterol is not the sine qua non for the production of cholesterol gallstones.     

Association between cholesterol-phospholipid vesicles and cholesterol crystals in human gallbladder bile

Rapid aggregation of cholesterol-phospholipid vesicles in gallbladder bile seems to be the first event in the production of cholesterol crystals, a prerequisite for cholesterol gallstone formation. We examined the amount of these vesicles in 33 human gallbladder biles in relation to biliary lipid composition and to the presence of cholesterol crystals. Biliary microscopy detected cholesterol crystals in all 19 biles from patients with cholesterol gallstones but in none of 14 biles from patients with pigment stones. Gel chromatography was used to separate vesicles and micelles in the native bile with an eluting buffer containing 10 mM sodium cholate to prevent disruption of micellar lipids. Cholesterol, phospholipid and bile salt concentrations were measured in every fraction collected. Bile acid, phospholipid, cholesterol and total lipid concentrations were not significantly different in samples with and without cholesterol crystals. The cholesterol saturation index (1.4 +/- 0.11 vs. 1.0 +/- 0.08) was significantly (p less than 0.01) higher in biles with crystals than without crystals. Gel filtration revealed a vesicular peak in addition to micellar fraction in 18 (23.1 +/- 3.2% of total cholesterol) of the 19 biles with crystals but only in three (15.7 +/- 2.4% of total cholesterol) of 14 biles without crystals. There was no relation between biliary lipid concentration or the cholesterol saturation index and the percentage of vesicular cholesterol in biles with or without crystals. The close association of vesicles and crystals in human gallbladder bile supports the contention that vesicles are important in the initial nucleation of cholesterol monohydrate crystals.     

Is Duodenal Bile Representative of Gallbladder Bile: A Comparative Study

Thirty-nine patients with cholelithiasis were prospectively studied to evaluate the qualitative and quantitative differences between duodenal bile and gallbladder bile. Duodenal bile obtained before cholecystectomy by nasoduodenal intubation and ceruletide injection was qualitatively similar to gallbladder bile obtained during surgery. Microscopic cholesterol crystals as an indicator of cholesterol gallstones (n = 35) could be detected in 31 (89%) and 35 (100%; p = NS), respectively. Moreover, there was no difference in the molar percentage of three biliary lipids and the mean cholesterol saturation index (1.54 0.72 and 1.74 0.42; p = NS) of the two sources of bile. Duodenal bile was, however, dilute as compared with gallbladder bile, as evidenced by lower cholesterol crystal counts (167 247 versus 705 978;p< 0.01), lower total lipid concentration (5.8 2.7 versus 11.1 5.6 g/dl;p < 0.001), and lower concentrations (in mmol/l) of the three bile lipids–that is, total bile acids, phospholipids and cholesterol (p < 0.001). Good concentrated bile (total lipid concentration =5 g/dl) could be obtained in 74% of duodenal bile samples, compared with 90% of gallbladder bile (p = NS). Our study shows that, although duodenal bile is dilute as compared with gallbladder bile, it is qualitatively similar to gallbladder bile and, because of the ease and safety of its collection, can be used to study serial alterations in biliary composition in individual subjects.     

Lipid composition of bile in diabetics and obesity-matched controls.

Duodenal bile from 27 diabetes was compared with samples from healthy subjects matched for age, sex, and body mass index. Cholesterol saturation and the molar percentages of bile acids, phospholipids, and cholesterol were not significantly different. Most bile samples were supersaturated in both groups. The maturity onset diabetics who were almost all obese had more saturated bile than the slimmer juvenile onset patients. Body fatness and plasma triglyceride levels were both positively correlated with the cholesterol saturation of bile in the controls but not in the diabetics. Bile was less concentrated in female diabetics than in controls, which is consistent with impaired gallbladder emptying. It is possible that the increased prevalence of gallstones in diabetics is due not so much to diabetes itself as to the frequently associated obesity.     

Abnormal Duodenal Bile Composition in Patients With Acalculous Chronic Cholecystitis

Objective : Our goal was to characterize biliary lipid composition in patients with the syndrome of chronic biliary pain, absence of gallstones, and inflammation of the gallbladder mucosa (acalculous chronic cholecystitis). Methods : Duodenal bile, obtained from 27 patients with a history of right upper quadrant pain and with negative imaging studies of the biliary tract, was analyzed enzymatically for bile acids, phospholipids, and cholesterol. Fifteen patients were found to have inflammation and/or fibrosis of the gallbladder at cholecystectomy. Results : The 15 patients with abnormal gallbladder histology had more dilute duodenal bile, as indicated by a low bile acid concentration and a lower proportion of phospholipids (   p < 0.01  ) when values were compared with those of duodenal bile samples from postmenopausal women without gallbladder disease or from radiolucent gallstone subjects participating in the National Cooperative Gallstone Study. Cholecystectomy relieved pain in 9 of 14 patients. Conclusions : Some patients with acalculous chronic cholecystitis have duodenal bile samples characterized by a decreased bile acid concentration and a decreased proportion of biliary phospholipids. The low biliary bile acid concentration may result from impaired gallbladder contraction and/or secretion by the biliary tract epithelium. The low proportion of phospholipid may result from posthepatic hydrolysis of luminal phosphatidylcholine followed by absorption of the hydrolysis products. The latter process could be caused by and/or contribute to mucosal inflammation and would also elevate the cholesterol saturation of bile, increasing the risk for cholesterol gallstone formation.     

Biliary lipid composition in patients with nonoperated Crohn's disease

Lipid composition of fasting duodenal bile was studied in 56 patients with nonoperated Crohn's disease, 21 normals matched for age and sex, 13 patients with cholesterol cholelithiasis, and 9 patients with ileal resections. Crohn's patients had a significantly higher mean saturation index, calculated according to Thomas (0.84±0.51) when compared to normal (0.63±0.25). Patients with ileocolonic Crohn's disease and patients with severe bile acid malabsorption, particularly, showed an increased incidence of cholesterol saturated bile. Saturation in patients with nonoperated Crohn's disease was not increased to the levels found in patients with ileal resection or cholesterol gallstones. Bile acid composition of gallbladder bile was characterized by a significant decrease of thedeoxycholate fractions in patients with Crohn's ileocolitis and colitis as well as in ileal resected patients. These qualitative changes of bile acid composition may influence cholesterol solubility. It is concluded that patients with nonoperated Crohn's disease may have an increased risk of developing cholesterol gallstones.     

Solubility of cholesterol in bile salt-lecithin model systems

Cholesterol solubility was determined in model systems of unconjugated and conjugated bile salts and lecithin at physiologic concentrations. Conjugated bile salts had somewhat less dissolving power than unconjugated forms, with taurine conjugates showing less power than glycine conjugates. Lecithin increased the dissolving power of each bile salt species proportionally up to a lecithin-bile salt molar ratio of 1.0, at which point the amount of cholesterol dissolved was triple that in the absence of lecithin. At most physiologic ratios of lecithin-bile salt, however, lecithin only doubles the amount of cholesterol dissolved. Lecithin reduces, but does not eliminate, significant differences in the cholesterol dissolving power of both unconjugated and conjugated bile salt species. Mixtures of unconjugated bile salts show a simple additive effect in the absence of lecithin, but when lecithin is present the dissolving power of deoxycholate predominates over cholate, and of cholate over chenodeoxycholate. Mixtures of conjugated bile salt species produce a simple additive effect on dissolving power in both the presence and the absence of lecithin. Our cholesterol saturation curves for glycodeoxycholate and glycocholate at a total bile salt concentration of 150 mM, which we consider representative of the cholesterol dissolving power of human gallbladder bile, showed less dissolving power at lecithin-bile salt ratios of 0.25 to 0.50 than did the curve of Adminrand and Small; our curves were reasonably similar to those of Hegardt and Dam on the trilinear graph. Our studies show that changes in total bile salt concentration encountered in human gallbladder bile do produce significant shifts in the saturation curve.Supported by Research Grant AM-09368 and Training Grant T1-AM-05314 from the National Institute of Arthritis and Metabolic Diseases, US Department of Health, Education and Welfare.Presented in part at the annual meeting of the Southern Society for Clinical Research on January 28, 1967, at New Orleans, Louisiana.     

Effects of fenofibrate on biliary lipids and bile acid pool size in patients with type IV hyperlipoproteinemia

Lipid-lowering drugs, notably clofibrate, may induce a supersaturation of bile with cholesterol, thus favouring the development of cholelithiasis. In order to see whether or not fenofibrate, a clofibrate analogue, has any influence on biliary cholesterol saturation, we determined the lipid composition of gallbladder bile and the bile acid pool size in 15 patients with type IV hyperlipoproteinemia before and after 6-8 weeks of treatment with a daily dose of 300 mg of the drug. At the end of treatment plasma triglycerides were markedly decreased, whereas no detectable influence on liver cell integrity or bile excretory function could be demonstrated in any patient by comparing the pre- and post-treatment serum levels of liver enzymes, bilirubin and bile acids. The mean bile cholesterol saturation index did not significantly change and cholic acid was the only bile acid to increase significantly. In the 3 patients with an initial saturation index of less than 1, bile became supersaturated with cholesterol. However, in no case were the limits of the metastable phase for cholesterol solubility in bile exceeded. Though only long-term prospective studies may give a definitive answer about the lithogenic potential of fenofibrate, our data on gallbladder bile composition in patients with type IV hyperlipoproteinemia indicate that it is not very likely that fenofibrate administration will increase the risk of gallstone formation in severely hyperlipidemic patients.     

Deoxycholic acid in gall bladder bile does not account for the shortened nucleation time in patients with cholesterol gall stones.

The relations between the concentration of deoxycholic acid (DCA), the cholesterol saturation index, and the nucleation time in gall bladder bile were measured to determine the role of DCA in bile in the pathogenesis of cholesterol gall stone disease. Bile was obtained from patients with cholesterol gall stones (n = 30), subjects without gall stones (n = 35), and patients with pigment gall stones (n = 9). Three of 30 cholesterol gall stone patients and 10 of 35 gall stone free subjects were treated with antibiotics by mouth to decrease the concentration of bile DCA and determine the effect of DCA on biliary lithogenecity. Both the percentage and concentration of DCA in bile were similar in patients with and without cholesterol gall stones despite significant differences in their cholesterol saturation indices and nucleation times. Neither the percentage nor the concentration of DCA in bile correlated with either the cholesterol saturation index or the nucleation time. Analysis of subgroups with matching cholesterol saturation indices showed no correlation between the proportion of DCA in the bile and the cholesterol nucleation time. The proportion of DCA in bile was decreased by antibiotic treatment, but this had no effect on the cholesterol saturation index or nucleation time. These results suggest that DCA in bile is not responsible for biliary cholesterol saturation or cholesterol nucleation time.     

The effect of sodium oleate on cholesterol solubility in bile salt-lecithin model systems

Reflux of pancreatic secretions and bacterial infection have been suggested as important factors in gallstone formation in some instances by introducing into bile phospholipases hydrolyzing lecithin to lysolecithin, mono- and diglycerides, and free fatty acids. Since there is little data on free fatty acids, we studied the effect of sodium oleate, the soap of one of the major fatty acid derivatives of lecithin, on cholesterol solubility in unconjugated bile salt-lecithin model solutions to see if an increase in this component might lead to saturation of bile with cholesterol. In the absence of lecithin, sodium oleate decreased cholesterol solubility in bile salt solutions at concentrations physiologic for bile, although cholesterol solubility was increased by oleate at higher oleate-bile salt ratios. In the presence of lecithin, sodium oleate decreased cholesterol solubility at all concentrations studied. Significant differences in cholesterol solubility were found for all comparable concentrations of sodium cholate and deoxycholate studied, both in the presence and absence of lecithin. Our studies showed that an increase in free fatty acid concentration can increase cholesterol saturation significantly in unconjugated bile salt-lecithin model solutions. Whether or not free fatty acid concentrations in pathologic bile reach levels sufficient to contribute to cholesterol saturation and gallstone formation cannot be determined until more adequate data on the minor lipid composition of bile becomes available.Supported by Research Grant AM-09368 and Training Grant T1-AM-05314 from the National Institute of Arthritis and Metabolic Diseases U.S. Department of Health, Education and Welfare.     

Biliary lipid and bile acid composition in insulin-dependent diabetes mellitus arguments for increased intestinal bacterial bile acid degradation

Bile cholesterol saturation and bile acid composition was studied in 12 nonobese male insulin-dependent diabetics and 28 controls. The total bile lipid concentration in the bile rich duodenal aspirate was lower in the diabetics. The bile cholesterol saturation index was lower in the diabetics if calculated according to Thomas and Hofmann, but not if calculated according to Carey's critical tables. A negative correlation was observed between the cholesterol saturation index of the bile of the diabetics and their long-term metabolic control, as measured by the percentage HbA_1c. No correlation existed between the saturation index and the metabolic control at the time of bile sampling as measured by serum glucose, beta-hydroxybutyrate, free fatty acids, and triglycerides. There was also a negative correlation between the cholesterol saturation index and the serum cholesterol concentrations. The glycine-taurine ratio of the conjugated bile acids was increased in the diabetics, as was the percentage concentration of secondary bile acids (deoxycholic acid and lithocholic acid). No correlation was found between the metabolic control of the diabetic state and either the glycine-taurine ratio or the percent concentration of secondary bile acids. These results do not favor a higher incidence of cholesterol gallstones in male juvenile-onset insulin-dependent diabetics. The increased glycine-taurine ratio of the conjugated bile acids and the elevated concentration of secondary bile acids may be due to increased bacterial invasion of the small intestine or decreased absorption of bile acids in the terminal ileum in these insulin-dependent diabetics.     

Diagnostic value of fine-needle puncture of the gallbladder: Side effects,safety, and prognostic value

Bile sampling without the risk of contamination by pancreatic and duodenal secretions and avoiding unpredictable influences of general anesthesia during biliary surgery on biliary analytics are feasible with percutaneous puncture of the gallbladder. In 207 patients with gallstones, gallbladder puncture was performed under local anesthesia with a 22-gauge spinal needle under continuous real-time ultrasound guidance. Bile samples were investigated for biliary lipids and nucleation time. Complete aspiration of gallbladder bile could be achieved in all patients without complications such as bleeding, bile leak, or inflammation. Of these patients, 11.6% reported mild abdominal problems, 3.4% required analgetics, and in 1.0% biliary colics were observed. Elective cholecystectomy was performed in 1 patient. Of the bile samples, 10.1% were contaminated with bactobilia. Biliary lipids, cholesterol saturation index (CSI), total lipid concentration (TLC), and bacteriological contamination were independent of gallstone number, whereas patients with solitary gallbladder stones exhibited a significantly longer nucleation time (NT) in comparison with those with multiple stones. In patients with gallstones, fine-needle puncture of the gallbladder represents an important diagnostic procedure and can be performed within minutes without major side effects if performed by an experienced sonographer.