Increased blood levels of methyl tert-butyl ether but not of ethyl propionate during instillation with contact gallstone dissolution agents in the pig

Esch, Oliver; Schteingart, Claudio D.; Pappert, D.; Kirby, D.; Streich, Rita; Hofman, A. F.

doi:10.1002/hep.1840180222

Cited by 10 publications

(1 citation statement)

References 37 publications

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“…A new solvent, ethyl propionate, was tested and found to dissolve gallstones nearly as rapidly as MTBE. Ethyl propionate did not induce nausea in contrast to MTBE because of rapid removal from plasma ( 440 ). Patients were treated successfully ( 441 ).…”

Section: Topical Dissolution With Organic Solventsmentioning

confidence: 99%

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

Hofmann

Hagey

2014

Journal of Lipid Research

298

284

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conceptions are rare, and provocative judgments stand the test of time. Let us also hope that this effort will be both useful and entertaining. Each of the topics discussed merits at least a full length article, so there will be, of necessity in many instances, consideration of only what we perceive to be the highlights. THE EBB AND FLOW OF MEDICAL INTEREST IN BILE ACIDSAfter the elucidation of the true chemical structure of bile acids in 1932 (see below), there was little interest in bile acids in the Western world. One exception to this statement was the laboratory of Siegfried Thannhauser, who wrote the fi rst textbook of metabolic biochemistry in Germany. He studied cholesterol and bile acid balance in the biliary fi stula dog ( 1 ). During this time, bile acids were sold as liver tonics and laxatives, but there were no placebo-controlled studies showing effi cacy. Indeed, bile acids were considered by the medical profession to have no useful therapeutic properties. The tri-oxo derivative of cholic acid (called "dehydrocholic acid") was known to induce bile fl ow in animals ( 2 ), and was occasionally used to stimulate bile fl ow in patients; but again there were no controlled studies showing effi cacy in hepatobiliary disease.

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Section: Topical Dissolution With Organic Solventsmentioning

confidence: 99%

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

Hofmann

Hagey

2014

Journal of Lipid Research

298

284

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Toxic effects of cholelitholytic solvents on gallbladder and liver

et al. 1995

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We evaluated the toxic effects of four currently used chemolytic solvents--dimethyl sulfoxide (DMSO, 99%), ethyl propionate (EP, 99%), tetrasodium ethyl-dimethyl tetraacetate (4Na-EDTA, 2%, pH 11), and methyl tert-butyl ether (MTBE, purity = 99.5%) in an animal model. Each solvent was tested in nine farm piglets (Landrace), weighing between 20 and 25 kg. A solvent-resistant catheter was inserted transhepatically into the gallbladder (GB) using sonographic guidance 24 hr prior to each experiment. Seventy-five milliliters of each solvent was infused over 3 hr into the gallbladder. The following day, a laparotomy was performed in order to assess for possible damage to the liver, GB, bile ducts (BD), or intestines. The GB and liver were resected and their histology examined. The following pathologic grades were assigned to GB, BD, and liver specimens to describe the tissue damage: normal (0), mild (1), moderate (2), and severe (3). We found that DMSO had the highest score on gallbladder and bile duct injury (49, 3), followed by EP (36, 2), EDTA (14, 1) and MTBE (16, 0), respectively; the difference in gallbladder damage was statistically significant. Very mild hepatocyte damage was present in the DMSO (2) and MTBE (2) groups. The administration of EP and EDTA resulted in no liver injury at all. Piglets within each treatment group suffered from varying degrees of tissue injury. No deaths were attributed to the administered solvents. We concluded that DMSO, EP, EDTA, and MTBE do not have serious local toxic effect on the GB, BD, and intestine; nor do they lead to severe hepatotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

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Gallbladder stone recurrence after medical treatment do gallstones recur true to type?

et al. 1995

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Medical treatments that dissolve or remove gallbladder stones but leave the gallbladder in situ have the disadvantage of gallstone recurrence. Little is known about the composition of recurrent stones or whether they recur true to type. In 21 patients with recurrent stones detected 5-74 months (mean +/- SEM, 26 +/- 4 months) after being rendered stone-free with dissolution therapy (N = 15) or percutaneous cholecystolithotomy (N = 6), we compared pretreatment and postrecurrence gallstone number, maximum gallstone attenuation scores measured by computed tomography (CT) and, in 13, the dissolvability of the recurrent stones with oral bile acids +/- extracorporeal shock-wave lithotripsy. Before treatment, five patients had solitary and 16 had multiple stones but on recurrence, the gallstones differed in number from the primary stones in 10 of the 21 patients. As a result of patient selection, before dissolution, the primary stones were all radiolucent with maximum CT scores of < 100 Hounsfield units (HU) (mean 45, range 10-84 HU). On recurrence, the stones were again CT-lucent in 13 of the 15 patients but were CT-dense in the remaining two (118 and 176 HU). Initially, all six patients treated by percutaneous cholecystolithotomy had radio-opaque stones, with a mean CT score of 459 (range 100-969) HU. However, on recurrence, only one had calcified stones (HU 140); the remaining five had CT-lucent stones (16-98 HU, P < 0.05). Of the 13 patients whose recurrent, plain x-ray-lucent and CT-lucent stones were treated with oral bile acids +/- lithotripsy, 12 (92%) showed evidence of gallstone dissolution. We conclude that gallbladder stones do not recur true to type in up to two thirds of patients. However, irrespective of original gallstone composition, recurrent stones are usually radio- and CT-lucent, presumed cholesterol-rich, and therefore potentially dissolvable with oral bile acids.

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Increased blood levels of methyl tert-butyl ether but not of ethyl propionate during instillation with contact gallstone dissolution agents in the pig

Cited by 10 publications

References 37 publications

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

Toxic effects of cholelitholytic solvents on gallbladder and liver

Gallbladder stone recurrence after medical treatment do gallstones recur true to type?

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