[VALUE OF BILOPTIN IN THE RADIODIAGNOSIS OF THE BILIARY TRACT].
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Lumbar myelography was carried out with the contrast media Amipaque, Dimer X and Myelografin in 10 patients each. Five of the patients treated with each contrast medium were kept in a sitting position after the examination, the others lay flat. Blood levels and excretion were measured up to 24 h. The results are interpreted as follows: 1. After lumbar injection of the contrast media there is a short phase of distribution in the subarachnoid space (lag time) and they then are transferred into the blood with a half-life of 3.9 +/- 2.4 h. The transport from the CSF is almost completed approximately after 24 h. The velocity of transport varies greatly between the individual patients. Watersoluble contrast media presumably flow passively with the CSF through the arachnoid villi into the venous blood. 2. The horizontal position of the patient reduces the lag time until the beginning of the actual transfer of the contrast medium. 3. The transfer of Dimer X begins somewhat later compared with Amipaque and Myelografin.
Several anionic substances used for cholecystography inhibit the development of protrusions in isolated hepatocytes in response to phalloidin. Drugs from the iopodate family were equieffective with those of th iodipamide type. The above protective effect results from a competitive inhibition of the phallotoxin uptake as shown for iopodate. Cholecystographic agents similarly inhibit the inward transport of cholic acid in a competitive manner. The inhibition of the phallotoxin response is inversely correlated with the uptake of 3H-demethylphalloin (r = 0.94) and with the inward transport of cholate (r = 0.84) at various inhibiting concentrations of iopodate.
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(1) Solubilization of Telepaque in the intestine is a limiting factor in the rate of intestinal absorption. Bilopaque and Oragrafin are more water-soluble and appear to be better absorbed than Telepaque. (2) Bile salts in the intestinal lumen increase the solubility of Telepaque. Therefore, a fatty meal administered with the Telepaque is desirable to evacuate bile salts from the gallbladder into the intestine. This is not required for the more water-soluble agents, Biopaque and Oragrafin. (3) The degree of protein binding of the contrast agents can be related to the degree of toxicity. Cholografin is the most highly bound and is the most toxic. (4) Hepatic receptor proteins may specifically bind the biliary contrast agents. This may be the reason that the renal contrast materials are poorly escreted in bile compared to the biliary contrast agents. (5) Telepaque is conjugated in the liver with glucuronide making the compound more soluble in bile. This prevents precipitation of Telepaque in the gallbladder and avoids reabsorpiton from the intestine. (6) The biliary excretion of Telepaque is facilitated by bile salts. Therefore, the administration of a fatty meal with Telepaque not only increases the rate of intestinal absorption of Telepaque but also the rate of biliary excretion. (7) The rate of biliary excretion of both the oral and the intravenous contrast agents appears to be limited by a hepatic transport maximum. Above a certain dose, increased amounts of the contrast agents do not result in more rapid excretion of the agents into bile. Rapid infusion of intravenous contrast agents results in high plasma concentration and greater urinary excretion, without increasing the biliary excretion. It does not appear to be indicated in clinical practice. (8) The biliary concentration of the contrast agents used for intravenous cholangiography is determined by their rate of biliary excretion, the choleretic effect of the contrast agent, and factors that determine the rate of basal bile flow. Fixed coupling of water with the biliary excretion of these contrast agents imposes an inherent limitation on the concentration of the contrast agent in bile. It appears that the biliary concentration of the intravenous contrast materials can be increased by having the patient fast prior to intravenous cholangiography. This decreases the enterohepatic circulation of bile salts and the rate of bile-salt-dependent bile flow. (9) Failure of the gallbladder to visualize after administration of Telepaque when there is adequate biliary excretion may be due to cystic duct obstruction, failure of the inflamed gallbladder mucosa to reabosrb water, or reabsorption or the contrast agent by the diseased gallbladder mucosa. (10) Maximum concentration of Telepaque occurs at 14-19 hr after ingestion. It is at this time that radiographs of the gallbladder should be made. With Bilopaque, peak concentration occurs at 10 hr so radiographs can be made earlier when Bilopaque is used.
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Isolated perfused rat livers were used for investigating possible interactions between two simultaneously injected contrast media, and which technique, using parenteral application of cholegraphic media, is optimal. The results show that excretion of a parenteral contrast medium is reduced by giving an oral contrast medium at the same time. Simultaneous administration of two different contrast media therefore does not result in improved diagnostic information. The effect depends on the dose, and a sufficiently long interval should be observed between giving an oral and a parenteral contrast medium. A comparison of excretion values following injection of a bolus and prolonged infusion shows higher biliary contrast concentration and increased excretion after a single injection. Comparing only the period after the infusion, no difference was found between these two methods of administration. The single injection offers pharmacokinetic advantages, but an infusion is better tolerated and has fewer side effects. A rapid infusion of 10 to 15 minutes is therefore recommended as the optimal means of administration.
In order to determine whether cholecystography and computed tomography (CT) are capable of better gallstone characterization than conventional radiography alone, 91 patients (76 females, 15 males; mean age 47 +/- 12 years) with symptomatic single gallstones were studied prospectively prior to extracorporeal shock-wave lithotripsy with concomitant oral stone dissolution therapy. In addition, the value of oral cholecystography in demonstrating patency of the cystic duct was compared with ultrasound assessment of gallbladder function. Despite "negative" plain gallbladder radiographs in all patients, oral cholecystography showed significant stone calcification in 8 of the 91 patients and CT showed stone calcifications in 52 of the 91 patients. In 12 patients the maximum stone density was between 50 and 90 Hounsfield units, and in 40 patients it was more than 90 Hounsfield units. CT revealed ring-like calcification in the majority (79%) of these stones. Oral cholecystography showed satisfactory concentration of contrast medium in all patients, while ultrasonography of the gallbladder following a chemically defined test meal demonstrated contractility of more than 50% of initial volume in 69 patients and of less than 30% in 9 patients. Although oral cholecystography is a simple, readily available complication-free method, ultrasound assessment of gallbladder contraction is better for selecting patients for extracorporeal shock-wave lithotripsy. CT allows significantly better characterization of gallstones than oral cholecystography and conventional plain gallbladder radiography.
Decrease in gall-bladder surface area, as obtained by ultrasound, was measured in 52 patients with insulin-dependent diabetes (27 with and 25 without autonomic neuropathy) 60 minutes after administration of the bile stimulant Biloptin. The post-stimulation area was 33 +/- 6% of initial value in patients with autonomic neuropathy, and 67 +/- 8% (P less than 0.0005) in those without autonomic neuropathy. Comparison with insulin-dependent chronic diabetics matched for sex, age and duration of illness, demonstrated that heart-rate variability in cholelithiasis was less than in the control subjects (P less than 0.05). It is concluded that autonomic neuropathy, measured by the occurrence of spontaneous vagotomy, in insulin-dependent diabetics is an important risk factor in the overall pathogenesis of cholelithiasis.
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Interest in the pharmacokinetics of cholecystopaques initially centered on transport from blood to bile. The data obtained in this effort have been valuable and have shown that the maximal iodine concentration achievable in the bile is quite similar for all of the currently available compounds. This concentration is, of course, dose dependent. the transport of contrast material from the bowel to the blood has been shown to be quite variable. Considerable progress was made in understanding this. The tremendous differences in absorption of iopanoic acid depending upon the pH of the administered solution was an initial revelation. The development of the concept that there is a water layer through which the cholecystopaque must pass before reaching the lipid membrane of the intestinal cell has added clarity to understanding the difference in absorption between water-soluble and water-insoluble cholecystopaques. A complete knowledge of what might enhance or inhibit absorption is not known. There is beginning to be an understanding of how intestinal dose relates to plasma levels. This should lead to an optimal dose-timing scheme for each cholecystopaque. The basic assumption is that the highest iodine concentration in the gallbladder leads to the most accurate cholecystography. If this is true, the gallbladder needs to be offered bile at the maximum concentrations during the period preceding filming. To accomplish this, the appropriate plasma level necessary for maximum excretion is needed. Experimental data suggest that our current clinical methods in regard to dose and dose timing need revision to optimize cholecystography. This revision needs to take place with a careful look at toxicity. Accepting the present premise that oral cholecystography can be improved, perhaps without a significant increase in morbidity, a fundamental question to be asked is: is it worth it?
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Three oral cholecystographic contrast media have been compared, mainly with regard to their ability to outline the gall bladder and also the frequency of undesirable side-effects that they produce. No significant differences were found between the media, and the final choice of a suitable medium for use in X-ray departments may depend on their relative cost. In times of financial restraint, such a decision might increasingly involve hospital pharmacists.