Results of a multicenter trial using a mechanical lithotripter for the treatment of large bile duct stones.

A prospective, uncontrolled trial of the use of a prototype mechanical lithotripter was performed in 116 patients at nine centers. Standard endoscopic approaches had failed to remove all stones, primarily because of large size (80% of patients). For 92% of patients, common bile duct stones were successfully captured and fragmented following the use of this lithotripter. The frequency of pancreatitis and hemorrhage was no greater than with standard endoscopic retrograde sphincterotomy, and complications unique to lithotripter use were not noted. For endoscopists skilled in therapeutic duodenoscopy, this modality should be considered in management of common bile duct stones refractory to standard techniques.

Spontaneous passage of glass beads from the canine gallbladder: facilitation by sphincterotomy.

To investigate the mechanism by which ablation of the sphincter of Oddi prevents gallstone formation, we assessed passage of glass beads out of the gallbladders of dogs with sphincterotomy and sham sphincterotomy. One month after bead implantation, dogs with an intact sphincter passed 52%, 26%, 22%, 10%, 0%, and 0% of beads with diameters of 2, 3, 4, 5, 6, and 8 mm, respectively. For the same respective bead diameters, dogs with a sphincterotomy passed 90%, 90%, 88%, 75%, 75%, and 42% of beads (p less than 0.05 for all bead diameters). No beads were in the common bile duct of any dog. In separate dogs studied by cholescintigraphy, sphincterotomy significantly increased gallbladder ejection fraction from 0.46 to 0.76 (p less than 0.01). In addition, sphincterotomy significantly lowered resting gallbladder volume from 24.4 to 15.8 ml (p less than 0.025) and lowered cholecystokinin-stimulated gallbladder volume from 13.3 to 5.9 ml (p less than 0.025). These data indicate that even with an intact sphincter, small solids can pass from the gallbladder and into the duodenum. Sphincterotomy facilitates passage of solids, apparently by general improvement in gallbladder emptying. Facilitated passage of crystals, microliths, or small stones seems the most likely explanation for prevention of gallstone formation by sphincterotomy.

Endoscopic sphincterotomy for suspected dysfunction of the sphincter of Oddi.

Fifty-one patients who underwent endoscopic sphincterotomy for suspected dysfunction of the sphincter of Oddi were evaluated retrospectively. The procedure resulted in complete abolition of pain allowing discontinuation of analgesics in 31 of the 46 patients available for follow-up. Patients with a dilated bile duct and delayed drainage of contrast material as demonstrated at endoscopic retrograde cholangiopancreatography (ERCP) had a more favorable response to sphincterotomy than those with normal ductal findings (p = 0.01). There was a higher complication rate in those without ductal dilation and delayed drainage compared to those with these ERCP abnormalities (p = 0.03). Sphincter of Oddi manometry was obtained in 29 patients prior to sphincterotomy; 24 were available for follow-up. A favorable outcome for sphincterotomy did not correlate with manometric assessment, particularly in patients with an abnormal ductal system.

Sodium morrhuate stimulates granulocytes and damages erythrocytes and endothelial cells: probable mechanism of an adverse reaction during sclerotherapy.

Stimulated by a patient with dyspnea, thrombocytopenia, and leukopenia after sodium morrhuate sclerotherapy, we studied the effect of this agent on the plasma coagulation and complement systems, the formed elements of the blood, and cultured human endothelial cells. The addition of sodium morrhuate to citrated plasma did not cause clotting or shorten the prothrombin time or partial thromboplastin time. Incubation of a 1:100 dilution of the clinical sodium morrhuate preparation in heparinized plasma led to a modest rise in [C3a]. The addition of the drug (dilutions 1:50 to 1:300) to granulocytes caused prompt aggregation (and, at the higher concentrations, granulocyte cytotoxicity [trypan blue exclusion; lactate dehydrogenase release]), but the same dilutions failed to aggregate platelets. However, 0.05% morrhuate added to washed red blood cells caused a prompt 84.0% (+/- 0.8% SEM) hemolysis, rendering the supernatant buffer a potent platelet aggregant. Not only was this sclerosing agent toxic to granulocytes and red cells, but a 1:1000 dilution of the drug also caused the destruction of 35.5% (+/- 6.6%) of cultured endothelial cells as measured by chromium 51 release. Three other agents in current use (ethanolamine oleate, sodium tetradecyl sulfate, and polidocanol) were studied and found to cause effects qualitatively similar to those of sodium morrhuate. We conclude that these drugs cause phlebosclerosis not primarily through induction of plasma coagulation, but by directly damaging endothelium and red cells, triggering platelets, and aggregating granulocytes at the venous wall endothelium. These effects likely derive from the surfactant properties of sodium morrhuate as well as its high arachidonate content.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of effect of experimental ascorbic acid deficiency on bile acid metabolism, sterol balance, and biliary lipid composition in man.

Extensive studies in animal models indicate that subclinical ascorbic acid deficiency impairs the conversion of cholesterol to bile acid, elevates plasma cholesterol levels, and predisposes to development of cholesterol cholelithiasis. The present study was designed to see if this is also true in man. Five normal volunteers were hospitalized in a metabolic ward and placed on a controlled diet containing 3-4 mg of ascorbic acid each day. Ascorbic acid supplementation was given as follows: control period I (days 1-33), 75 mg/day; deficient period (days 34-96), 0 mg/day; and repletion period (days 97-101), 1000 mg/day. In addition, three of the subjects were studied during a second control period (days 102-139) during which they were given 75 mg/day of ascorbic acid. Ascorbate levels at the end of both control periods were 0.87-1.34 mg/dl in plasma and 19.4-29.5 micrograms/10(8) cells in leukocytes. At the end of the deficient period these levels were 0.09-0.15 mg/dl in plasma and 6.2-10.0 micrograms/10(8) cells in leukocytes, levels approaching those seen in scurvy. There was no effect of ascorbic acid deficiency on plasma cholesterol and triglycerides; plasma cholesterol in high, very low, and low density lipoprotein fractions; biliary lipid composition and saturation index of gallbladder bile; synthesis, fractional turnover, or pool size of either cholic or chenodeoxycholic acids; output of fecal acid or neutral sterols; and fecal sterol balance. Total bile acid pool size calculated by the one-sample technique was reduced 11% in the deficient period compared to control period I (P less than 0.005), and increased to 98.7% of the baseline levels in control period II. However, total bile acid pool calculated by the Lindstedt method did not change during deficiency. These data demonstrate that short-term subclinical ascorbic acid deficiency near the scorbutic range has no significant effect on bile acid and cholesterol metabolism in man.

Human T-cell function in experimental ascorbic acid deficiency and spontaneous scurvy.

Studies in animal models suggest that ascorbic deficiency impairs T-cell-mediated immunity. We studied five normal volunteers hospitalized on a metabolic unit and consuming a strictly controlled diet deficient in ascorbic acid I) after a 5-wk control period of ascorbic acid supplementation (75 mg/day) and 2) after a 9-wk period of no supplementation. Three of the subjects were restudied after a 5-wk period of ascorbic acid supplementation after the deficient period. At the end of both control periods ascorbic acid levels in plasma ranged from 0.9 to 1.3 mg/dl and in leukocytes from 19 to 30 microgram/10(8) cells. At the end of the deficient period levels of ascorbic acid in plasma ranged from 0.09 to 0.15 mg/dl and in leukocytes from 6.2 to 10 microgram/10(8) cells, levels at or below those frequently found in frank scurvy. None of the T-cell parameters tested including mitogen responsiveness to phytohemagglutinin and percentage of T-cells bearing receptors for IgM (helper cells) and IgG (suppressor cells) was different in the deficient period compared to the control periods. One patient with spontaneous scurvy (plasma ascorbic acid 0.07 mg/dl, leukocytic ascorbic acid 4.9 microgram/10(8) cells) was studied at the time of admission and after vigorous ascorbic acid repletion. All T-cell parameters after repletion were unchanged from admission. We conclude that in man ascorbic acid deficiency, even at the scorbutic level, does not alter T-cell numbers or impair in vitro T-cell function.

Inhibition of gallstone formation by sphincterotomy in the prairie dog: reversal by atropine.

Sphincterotomy has previously been shown to decrease gallbladder volume and gallbladder bile stasis while inhibiting gallstone formation in the prairie dog. We tested the possibility that atropine administration might reverse the effects of sphincterotomy on gallbladder mechanical function and gallbladder bile stasis and thereby reverse the inhibition of gallstone formation seen after sphincterotomy. Sixteen prairie dogs underwent sphincterotomy and were placed on a high cholesterol diet known to consistently induce gallstone formation. After 6 wk, in addition to the lithogenic diet, 8 animals were administered atropine. A control group of 8 animals was continued on the lithogenic diet. At death, animals that had undergone sphincterotomy and received atropine had a larger mean gallbladder volume (2.7 +/- 0.4 ml) than sphincterotomized control animals (0.66 +/- 0.2 ml, p less than 0.005), more total lipid stored in the gallbladder (176.1 +/- 33.9 mumol, sphincterotomy and atropine vs. 42.8 +/- 17.3 mumol, sphincterotomy, p less than 0.005), and a larger fraction of administered radiolabeled bile salt stored in the gallbladder (51.5 /- 7.3%, sphincterotomy and atropine vs. 24.5 +/- 10.7 sphincterotomy, p less than 0.05). The ratio of the fraction of [3H]cholic acid in the gallbladder (given 1 day before death) to the fraction of [14C]cholic acid in the gallbladder (given 4 days earlier) was lower for animals that underwent sphincterotomy and received atropine (0.63 +/- 0.04) than for sphincterotomized control animals (1.0 +/- 0.15, p less than 0.05), indicating a return of gallbladder bile stasis in the atropine-treated group. Confirming our previous work, only 1 of 8 animals that underwent sphincterotomy had gallstones. In contrast, 8 of 8 atropine-treated animals formed stones (p less than 0.005). Gallbladder bile of both groups were equally supersaturated with cholesterol. These findings provide direct support for the role of gallbladder bile stasis in the pathogenesis of cholesterol gallstone formation in this model.

Lack of effect of subclinical ascorbic acid deficiency upon antipyrine metabolism in man.

The influence of experimentally induced subclinical ascorbic acid deficiency upon antipyrine metabolism was assessed in five healthy male volunteers maintained in a hospital metabolic ward and fed a controlled diet deficient in ascorbic acid. Antipyrine pharmacokinetic parameters were determined four times during the study: at the end of an initial control period, after 28 and 63 days of depletion, and at the end of a second control period. No differences in antipyrine metabolism were observed despite the fact that the subjects had plasma ascorbate levels indicative of vitamin C deficiency (i.e., plasma levels less than 0.3 mg/dl) for 5 days (28 day-depletion) or 40 days (63 day-depletion). This experiment demonstrates that pronounced ascorbic acid deficiency of relatively short duration does not alter antipyrine metabolism in man.

Comparison of bile acid synthesis determined by isotope dilution versus fecal acidic sterol output in human subjects.

Fecal acidic sterol output has been found to be much lower than bile acid synthesis determined by isotope dilution (J. Lipid Res. 17: 17, 1976). Because of this confusing discrepancy, we compared these 2 measurements done simultaneously on 13 occasions in 5 normal volunteers. In contrast to previous findings, bile acid synthesis by the Lindstedt isotope dilution method averaged 16.3% lower than synthesis simultaneously determined by fecal acidic sterol output (95% confidence limit for the difference - 22.2 to -10.4%). When one-sample determinations of bile acid pools were substituted for Lindstedt pools, bile acid synthesis by isotope dilution averaged 5.6% higher than synthesis by fecal acidic sterol output (95% confidence limits -4.9 to 16.1%). These data indicate that the 2 methods yield values in reasonably close agreement with one another. If anything, fecal acidic sterol outputs are slightly higher than synthesis by isotope dilution.

Purification and properties of gentisate 1,2-dioxygenase from Moraxella osloensis.

Gentisate:oxygen 1,2-oxidoreductase (decyclizing) (EC 1.13.11.4; gentisate 1,2-dioxygenase) from Moraxella osloensis was purified to homogeneity as shown by polyacrylamide gel electrophoresis. The enzyme has a molecular weight of about 154,000 and gives rise to subunits of molecular weight 40,000 in the presence of sodium dodecyl sulfate. Gentisate 1,2-dioxygenase showed broad substrate specificity and attacked a range of halogen- and alkyl-substituted gentisic acids. Maleylpyruvate, the product formed from gentisate, was degraded by cell extracts supplemented with reduced glutathione, but substituted maleylpyruvates were not attacked under these conditions.