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T H Magnuson

Publications and source records attributed to T H Magnuson.

31 records · Page 2Linked to original sources

Short-term fasting increases biliary calcium and bilirubin.

Fasting has been associated clinically with the development of gallbladder sludge and pigment gallstones, both of which are composed primarily of calcium bilirubinate. Although fasting has been demonstrated to increase the cholesterol saturation of bile, its effect on biliary calcium and bilirubin has not been investigated. We, therefore, tested the hypothesis that short-term fasting would increase gallbladder bile calcium and bilirubin levels. Fifteen prairie dogs were studied. Seven animals were not fasted, whereas eight were fasted for 16 hr prior to acute experiments. Gallbladder and hepatic bile samples were obtained and analyzed for calcium, bilirubin, pH, and biliary lipids. Gallbladder bile ionized calcium levels were significantly increased in fasted animals (1.7 +/- 0.2 mM) compared to those in nonfasted animals (1.1 +/- 0.1 mM). Similarly, total calcium (4.3 +/- 0.5 mM vs 2.3 +/- 0.3 mM), total bilirubin (63 +/- 12 microM vs 29 +/- 8 microM), and bilirubin monoglucuronide (58 +/- 10 microM vs 22 +/- 8 microM) were significantly increased in the fasted group. Fasted animals were also noted to have an increased biliary cholesterol saturation index (0.57 +/- 0.04 vs 0.36 +/- 0.03) and decreased biliary pH (6.9 +/- 0.1 vs 7.6 +/- 0.1). These data indicate that in the prairie dog short-term fasting results in significant alterations in gallbladder bile composition. The increased concentrations of gallbladder calcium and bilirubin observed in these experiments may account, in part, for the formation of pigment gallstones and gallbladder sludge seen clinically with prolonged fasting.

Animals↗

The effect of calcium on gallbladder absorption.

The absorption of water and electrolytes is an important physiologic function of the gallbladder which is altered during gallstone formation. Extracellular calcium and calcium channel antagonists are known to affect intestinal absorption, yet their effect on gallbladder absorption is less well defined. We, therefore, tested the hypothesis that changes in extracellular calcium or in calcium channels would alter gallbladder absorption. New Zealand white rabbit gallbladders were removed, filled with a modified Krebs buffer (Ca2+ = 0.7 mM), and suspended in an oxygenated bath of the same buffer. Water absorption was determined gravimetrically by obtaining serial gallbladder weights at 10-min intervals. After a 40-min control period, the serosal bathing solution was changed to one of four experimental solutions (n = 6 for each group): Ca2+ = 0.25, 0.7, or 1.2 mM or Ca2+ = 0.7 mM plus 0.1 mM verapamil. Absorption was determined during an 80-min experimental period with results expressed as the percentage change in gallbladder absorption compared to that of the control period. The 0.25, 0.7, and 1.2 mM Ca2+ groups did not show a significant change in absorption rate from their respective control rates. However, the verapamil group did demonstrate a significant (P less than 0.05) decrease in absorption rate of -69 +/- 8% by the end of the experimental period. These data demonstrate that verapamil inhibits gallbladder absorption while changes in serosal calcium concentration have no effect. We conclude that calcium channels and intracellular calcium may play an important role in modulating gallbladder absorption.

Absorption↗

Altered bile composition during cholesterol gallstone formation: cause or effect?

Gallbladder stasis, increased gallbladder absorption, and elevated biliary levels of calcium, hydrogen ion, and bilirubin have been implicated as factors potentially critical to cholesterol crystal precipitation. Previous studies, however, have analyzed bile only when crystals or gallstones have already formed. Therefore, we tested the hypothesis that changes in bile composition are a late effect, occurring only after crystal formation. Adult male prairie dogs were fed a standard nonlithogenic control diet (n = 7) or a lithogenic 1.2% cholesterol diet for 5, 9, or 14 days to cause cholesterol saturation (n = 7), cholesterol monohydrate crystals (n = 7), or gallstones (n = 7). Gallbladder bile was examined microscopically for crystals, and analyzed for ionized calcium, bilirubin, pH, total protein, and biliary lipids. The ratio of gallbladder to hepatic bile radiolabeled cholic acid specific activity (Rsa) was calculated as an index of gallbladder stasis. Cholesterol saturation index was calculated. The results demonstrate that increased gallbladder bile cholesterol saturation and total protein concentration precede cholesterol monohydrate crystal precipitation. However, changes in gallbladder ionized calcium, unconjugated bilirubin, pH, stasis, and absorption were noted only after crystals and gallstones had already formed. These data indicate that alterations in gallbladder bile calcium, bilirubin, pH, stasis, and absorption are not early changes, but occur simultaneously with or after crystal formation. Increased biliary protein, however, which was elevated prior to nucleation, may be an important mediator of cholesterol precipitation in cholesterol-saturated bile.

Animals↗

The triad of Streptococcus bovis bacteremia, colonic pathology, and liver disease.

The association of Streptococcus bovis endocarditis and colon carcinoma has been reported previously in small series in the medical, but not surgical, literature. Although the fecal carriage rate of S. bovis increases with colonic pathology, no explanation exists for the development of bacteremia in these cases. To explore the possible contribution of hepatic dysfunction to the development of portal and systemic bacteremia, the incidence of both colonic pathology and liver disease or dysfunction was determined in 92 patients with S. bovis endocarditis and/or bacteremia. Colonic and liver evaluation had been undertaken in 47% and 93% of patients, respectively. Among these patients, colonic pathology was identified in 51%, and liver disease or dysfunction was documented in 56%. Either the underlying colonic disease or alterations in hepatic secretion of bile salts or immunoglobulins may promote the overgrowth of S. bovis and its translocation from the intestinal lumen into the portal venous system. A compromised hepatic reticuloendothelial system may then contribute to the development of S. bovis septicemia and subsequent endocarditis. We conclude that S. bovis bacteremia is an indication to the clinician of the possibility of underlying liver disease as well as colon pathology.

Colonic Diseases↗

Backscattered electron imaging and windowless energy dispersive x-ray microanalysis: a new technique for gallstone analysis.

Scanning electron microscopy with or without conventional energy dispersive x-ray microanalysis is currently used to identify gallstone microstructure and inorganic composition. Organic calcium salts are among many biliary constituents thought to have a role in gallstone nidation and growth. However, current analytical techniques which identify these salts are destructive and compromise gallstone microstructural data. We have developed a new technique for gallstone analysis which provides simultaneous structural and compositional identification of calcium salts within gallstones. Backscattered electron imaging is used to localize calcium within cholesterol at minimum concentrations of 0.01%. Windowless energy dispersive x-ray microanalysis produces elemental spectra of gallstone calcium salts which are qualitatively and quantitatively different. These combined techniques provide simultaneous structural and compositional information obtained from intact gallstone cross-sections and have been used to identify calcium salts in gallstones obtained at cholecystectomy from 106 patients.

Calcium↗

How many Americans will be eligible for biliary lithotripsy?

Extracorporeal shock wave lithotripsy has received increasing attention as a possible alternative to cholecystectomy. Good data, however, are not available on what percentage of the 500,000 Americans presently undergoing cholecystectomy annually might be eligible for extracorporeal shock wave lithotripsy. Therefore, we studied 100 consecutive adult patients undergoing cholecystectomy and applied present exclusion criteria to determine their suitability for extracorporeal shock wave lithotripsy. In each patient, preoperative history and operative findings were reviewed. Gallstone size and number were recorded, and cholesterol content and radiopacity were determined. Cholesterol stones were found in 74 patients, pigment stones in 21, and acalculous cholecystitis in 5. Of the 100 patients, only 19 (19%) had no exclusion criteria and, thus, would have been eligible for extracorporeal shock wave lithotripsy. These data suggest that approximately 95,000 Americans a year will be candidates for shock wave biliary lithotripsy.

Adolescent↗

Oral calcium promotes pigment gallstone formation.

Dietary calcium supplementation has been recommended for prevention of osteoporosis and has become a standard component of most "health food" diets. Biliary calcium has been recognized to play a central role in the formation of pigment gallstones. We have recently demonstrated that 5 days of oral calcium supplementation significantly increases biliary calcium in the prairie dog (K. D. Lillemoe, T. H. Magnuson, G. E. Peoples, et al., Gastroenterology 94: A563, 1988). We hypothesized, therefore, that long-term oral calcium supplementation would promote pigment gallstone formation. Sixteen adult male prairie dogs were maintained on a standard nonlithogenic diet. Eight animals received calcium supplementation (2.5 x control levels) in their water, while the remaining eight animals served as controls. After 8 weeks, cholecystectomy was performed, and the common bile duct was cannulated. Bile was examined microscopically and analyzed for ionized calcium, bilirubin, glycoprotein, and biliary lipids. The cholesterol saturation index (CSI) was calculated. Pigment stones and calcium bilirubinate sludge were present in all animals receiving calcium supplementation. Only one control animal had evidence of pigment stones (P less than 0.001). Biochemical analysis of gallbladder bile demonstrated a significant increase in total bilirubin and bilirubin monoglucuronide (P less than 0.01) as well as bile glycoprotein content (P less than 0.05) after oral calcium supplementation. Gallbladder bile ionized calcium was also increased although not significantly. These data suggest that oral calcium supplementation promotes gallbladder sludge and pigment gallstone formation in the prairie dog. This observation raises concern that oral calcium supplementation, especially in the older female population, may enhance gallstone formation.

Animals↗

The role of bacteria in gallbladder and common duct stone formation.

Debate continues as to the role that bacteria play in gallstone pathogenesis in Western countries. We therefore, examined gallbladder and common duct stones from 67 consecutive patients undergoing cholecystectomy and/or common bile duct exploration. Bile was cultured and stone cholesterol content was measured. Stones were examined by scanning electron microscopy (SEM) for bacteria. Individual calcium salts were classified by windowless energy-dispersive x-ray microanalysis. Gallbladder stones in 65 patients were identified as cholesterol in 46 (71%), black pigment in 17 (26%), and brown pigment in 2 patients (3%). Common bile duct stones from ten patients were cholesterol in 4, black pigment in 2, and brown pigment in 4 patients. The five patients with brown pigment stones were significantly (p less than 0.05) older, more likely to be men and to present with bile duct obstruction. Bile cultures were positive in 13% of patients with cholesterol stones, in 14% of those with black pigment stones, and in all of the patients with brown pigment stones (p less than 0.001). By SEM, bacteria were observed only within the calcium bilirubinate-protein matrix of brown pigment stones (p less than 0.001). In comparison to black pigment stones, brown stones were more likely to contain calcium palmitate (p less than 0.005) and cholesterol (p less than 0.001). We conclude that black and brown pigment stones have different pathogenic mechanisms and that bacterial infection is important only in the formation of brown pigment stones.

Adult↗

Caffeine prevents cholesterol gallstone formation.

Methylxanthines are known to inhibit in vitro gallbladder absorption. Increased gallbladder absorption has been observed during formation of cholesterol gallstones. Therefore we tested the hypothesis that caffeine would inhibit in vivo gallbladder absorption and thus prevent formation of cholesterol gallstones. Sixteen adult male prairie dogs received a control nonlithogenic diet, and 16 were fed a diet containing 1.2% cholesterol. Half of the animals in each group received caffeine in their drinking water. Gallbladder and hepatic bile were examined microscopically and analyzed for biliary lipids and electrolytes. The gallbladder/hepatic bile ratios of bile acids and sodium were calculated as indices of gallbladder absorption. All eight animals receiving the 1.2% cholesterol diet formed cholesterol gallstones, whereas none of the eight animals fed the cholesterol diet plus caffeine formed gallstones. The cholesterol saturation index was similar, however, in both groups. In animals fed a control diet, the administration of caffeine significantly increased hepatic bile flow and decreased the gallbladder/hepatic bile ratio for both bile acids (5.4 +/- 0.9 vs 3.6 +/- 0.3; p less than 0.05) and sodium (1.26 +/- 0.03 vs 1.12 +/- 0.03; p less than 0.01). In animals fed the high-cholesterol diet, caffeine significantly decreased the ratios for both bile acids (9.0 +/- 1.6 vs 5.3 +/- 0.6; p less than 0.05) and sodium (1.37 +/- 0.06 vs 1.21 +/- 0.01; p less than 0.05), lowered gallbladder bile protein levels, normalized gallbladder stasis, and lowered serum cholesterol levels. In summary, caffeine prevented formation of cholesterol gallstones in this experimental model. The effect of caffeine may be the result of alterations in multiple biliary parameters including the inhibition of gallbladder absorption.

Absorption↗

MR cholangiography in biliary obstruction using half-Fourier acquisition.

PURPOSE: Our goal was to evaluate biliary obstruction using a T2-weighted, turbo, SE MR sequence with half-Fourier acquisition (HASTE). METHOD: A prospective evaluation of 21 consecutive patients with clinical evidence of obstructive jaundice was carried out comparing HASTE MR cholangiography (MRC) to endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography. A control group of five normal volunteers was also evaluated. The study group was imaged with a 1.5 T MR scanner using a body coil. The HASTE sequence was applied in axial, coronal, and oblique sagittal planes. Ultrafast acquisition scanning times allowed the use of a single breath hold. Bile duct dilatation, level of obstruction, and cause of obstruction were assessed on both imaging modalities by two radiologists blinded to the clinical diagnosis and to each other's results. RESULTS: All studies were interpretable with anatomy well seen in 82% of the cases. MRCs of a normal control group were correctly interpreted. The presence of biliary dilatation was accurately depicted by HASTE MRC in 100% of patients with complete interobserver agreement. The level of obstruction was depicted correctly in 87% of patients with 93% interobserver agreement. The right main duct was seen by MRC in 80% of obstructed systems. The left main duct was seen in all obstructed patients. The gallbladder was identified in 88% of patients by MRC. Common bile duct stricture and stones could be differentiated as a cause of obstruction in all cases. CONCLUSION: MRC using the HASTE imaging sequence can safely and accurately depict the presence and level of biliary obstruction. The fast acquisition time of 13 s/scan makes the technique suitable for uncooperative and ill patients. HASTE MRC should be considered an alternative procedure to direct cholangiography in selected patients.

Aged↗

The diagnostic utility of HASTE MRI in the evaluation of acute cholecystitis. Half-Fourier acquisition single-shot turbo SE.

PURPOSE: The purpose of this study was twofold: (a) to determine the significance of high signal intensity surrounding the gallbladder as seen on T2-weighted HASTE (half-Fourier acquisition single shot turbo SE) MR images in patients with acute cholecystitis and (b) to determine the sensitivity of T2-weighted HASTE MR images in detecting gallbladder and common bile duct (CBD) calculi in patients with acute cholecystitis. METHOD: Seventy-two patients with a suspicion of acute cholecystitis were referred for HASTE MRI over a 2 year period. Forty-one patients underwent MRI after sonography and the remaining 31 patients before sonography. MR images were independently evaluated for the presence of MR pericholecystic high signal and gallbladder and CBD calculi. Findings were correlated with results obtained at sonography and at surgery. RESULTS: Of the 72 patients imaged with HASTE MRI, 55 had cholecystitis based on clinical, sonographic, and/or surgical findings. Of these, 45 had acute and 10 had chronic cholecystitis. HASTE MRI demonstrated MR pericholecystic high signal in 41 of 45 (91%) of the patients with acute cholecystitis. The sensitivity of HASTE MRI in diagnosing acute cholecystitis was 91%. The specificity was 79%. The positive predictive value was 87%, the negative predictive value was 85%, and the overall accuracy of the test was 89%. Gallbladder stones were seen by HASTE MRI in 38 of 41 (93%) of patients with acute calculus cholecystitis demonstrated at sonography. CBD stones were demonstrated by HASTE MRI in seven of nine (78%) patients and by sonography in five of nine (56%) patients with documented choledocholithiasis on conventional cholangiography. CONCLUSION: HASTE MRI has a high degree of accuracy in diagnosing acute cholecystitis based on the single finding of pericholecystic MR high signal. A similar level of accuracy is demonstrated in detecting gallbladder stones. Biliary duct calculi are detected with even greater accuracy than with sonography in patients with acute cholecystitis. Invasive preoperative endoscopic retrograde cholangiography may therefore be limited to only those patients with acute cholecystitis and CBD stones demonstrated on HASTE MRI. These features make HASTE MRI and ideal imaging modality in the initial evaluation of acute biliary pain and may ultimately replace sonography in the preoperative evaluation of acute cholecystitis.

Acute Disease↗