Search

The effect of fasting on gallbladder opacification during oral cholecystography was studied in 10 normal volunteers using 2 oral cholecystographic agents, iopanoic acid and sodium tryopanoate. Radiographs made 15 hours after ingestion of the contrast agents revealed good opacification of the gallbladder in all subjects when iopanoic acid was administered with a meal and when sodium tyropanoate was administered in the fasting state; in only 2 subjects when iopanoic acid was given in the fasting state; in 3 when given in the fasting state with ox bile; and in 3 when sodium tyropanoate was given with a meal.

The biliary and urinary excretion and the choleretic effect of iopanoic acid (Telepaque) were studied in nonanesthetized bile-fistula dogs using a stepwise increase of infusion rates of iopanoic acid and a constant infusion of sodium taurocholate at a rate of either 0.5 or 2.0 mumoles/min./kg. The maximum rate of bile excretion (0.671 mumoles/min./kg) when taurocholate was infused at the lower rate nearly doubled (1.325 mumoles/min./kg) when given at the higher rate. Maximum biliary concentrations of iopanoic acid at both rates of taurocholate infusion (70-77 mumoles/ml) were almost double the maximum concentration previously determined for iodipamide (Cholografin) (42 mumoles/ml).

Successful opacification of the gallbladder during oral cholecystography depends on adequate absorption of the contrast agent from the intestine. The present studies were undertaken to define the specific characteristics of the intestinal mucosa and the properties of the various contrast agents which determine their rates of intestinal absorption. The polarity of the compounds was established by determining the ratios of their distribution between bulk solvents (benzene and water). In addition, the maximum aqueous solubility of each compound was determined. Using in vivo cannulated segments of dog jejunum, apparent passive permeability coefficients were measured. From these data, the apparent maximal rate of intestinal absorption was calculated. The six cholecystopaques studied differed markedly in polarity as judged by their varying ratios of distribution between benzene and water. The permeability coefficients varied inversely with the polarity of the compounds. However, the incremental changes in the coefficients were considerably less than the corresponding changes observed in the partition ratios. The rates of absorption of the more polar contrast agents (tyropanoate, iopronic acid, and iocetamic acid) were greater than the less polar compounds (iopanoic acid, sodium ipodate, and calcium ipodate) under the conditions in which the resistance of the unstirred water layer is not rate limiting and where bile acid micelles are not present.

The biliary and urinary excretion and the choleretic effect of ioglycamide were studied in unanesthetized bile fistula dogs using stepwise increasing infusion rates to obtain multiple steady states. The results are compared with data from previously reported experiments in the same animals using iodoxamate and iodipamide. The rate of biliary excretion and the choleretic effect of ioglycamide are similar to those of iodipamide and iodoxamate. Like iodipamide and iodoxamate, the relation between infusion rate or plasma concentration and biliary excretion or concentration of ioglycamide are hyperbolic and can be fitted to saturation kinetics. Quantitatively, the excretion of ioglycamide and iodipamide are virtually identical. However, for any equimolar infusion rate or plasma concentration, more iodoxamate than ioglycamide is excreted in the bile. Despite the greater biliary excretion of iodoxamate, the maximum biliary concentration of ioglycamide, iodipamide, and iodoxamate is the same at low basal bile flow because the choleretic effects of the three compounds are equal. The data suggest that, theoretically, with any equimolar dose ioglycamide will be identical to iodipamide as a contrast material for intravenous cholangiography, but that iodoxamate may be superior to ioglycamide because more iodoxamate is excreted in the bile. This advantage of iodoxamate might become apparent clinically in patients with high basal bile flow or if smaller doses of the contrast material are used. However, at the presently recommended doses of the two compounds, it is unlikely that the use of ioglycamide for intravenous cholangiography will be any different than iodoxamate.

Conflicting data have been reported concerning the optimum dose and rate of administration of iodipamide required to obtain maximum radiographic opacification of the biliary tree during intravenous cholangiography. Experiments were performed in dogs to determine the effect of plasma concentration on the excretion and concentration of iodipamide in the bile and urine during a steady state of infusion and excretion. The data indicate that a hyperbolic relation exists between the plasma concentration and both the biliary concentration and the total biliary excretion. A mathematical expression of these relations is presented. At low plasma concentrations, iodipamide was not excreted in the urine. However, at high plasma concentrations, urinary excretion increased sharply. It appears that a biliary concentration of iodipamide sufficient to achieve adequate radiographic visualization of the biliary tree can be obtained without significant renal excretion by constant infusion of iodipamide at an appropriate rate in dogs. Stepwise increase in the infusion rate until adequate radiographic visualization is obtained may be the best method for performing intravenous cholangiography to obtain visualization with the least amount of iodipamide in order to minimize toxicity.

The use of a physician-nurse practitioner team is advocated as an approach to delivering better health care to patients in skilled nursing facilities. The application of this approach in a young community with an inadequate supply of primary physicians and 596 extended care beds is discussed. Patients derive benefit from more comprehensive health care delivered with greater attention to individual needs. Staffs of skilled nursing facilities enjoy improved communication with the medical team and better compliance with legal requirements. The team physician is able to use his time more effectively and provide medical supervision for a greater number of patients by sharing responsibilities with a nurse practitioner. Paper compliance, adherence to agency regulations, quality assurance, and payment are some of the problems encountered.

Cholografin and Renografin 76 were studied to determine their effects on platelet function. In vitro platelet aggregation was significantly inhibited by at least 3.4 micron/ml Cholografin and 19.5 micron/ml Renografin 76. Patients who received Cholografin for intravenous cholangiography, and Renografin 76 for non-cardiac angiography, had low levels of plasma contrast agent, and hemostasis was clinically unimpaired. Patients who received Renografin 76 for cardiac angiography had inhibition of platelet aggregation at high levels of plasma contrast agent; there was no correlation with prolonged bleeding times, or with bleeding complications. High levels of plasma contrast agent may inhibit platelet aggregation in vitro and in vivo, although this may not be associated with clinically significant bleeding.

It is well established that a number of organic anions are excreted by the liver into bile in association with a marked increase in bile flow. Previous studies have shown that iodipamide (3,3'-(adipoyl-diimino)bis[2,4,6-triiodobenzoic acid]), the radiographic contrast material used for intravenous cholangiography, is a potent choleretic. Experiments were performed in unanesthetized dogs to determine if the increased bile flow produced by iodipamide is canalicular or ductular in origin, to quantitate the choleresis associated with iodipamide and taurocholate excretion, and to correlate these findings with the results of in vitro studies in which the osmotic activities of iodipamide and taurocholate in both isotonic saline and bile were determined. The plasma erythritol clearance increase linearly with the excretion of iodipamide, indicating that iodipamide stimulates canalicular bile flow. The choleretic potency of iodipamide (22 ml/mmol) is approximately 3 times that of taurocholate (7.8 ml/mmol), yet the osmotic activity of iodipamide in bile (1.5 mosmol/mmol) is only twice as great as that of taurocholate in bile (0.8 mosmol/mmol). It therefore appears that, per unit of effective osmotic solute secreted, iodipamide carries more water into the bile canaliculi than does taurocholate.

A 16-year-old girl with recurrent pain in the right upper quadrant and abnormal results of liver function tests was found to have a large choledochal cyst filled with stones. Computerized tomography and endoscopic retrograde cholangiopancreatography showed the large cyst with innumerable primary cyst stones and an anomalous pancreaticobiliary duct junction.

The case of a patient with primary mesenteric venous thrombosis presenting with massive dilatation of almost the entire colon is described. The differential diagnosis suggested by this presentation is briefly discussed with special attention to the diagnosis of acute colonic pseudoobstruction. Possible reasons for the atypical presentation of acute mesenteric venous thrombosis should, therefore, be considered in the differential diagnosis of all patients presenting with colonic distention and pseudoobstruction.

The biliary and urinary excretion of sodium tyropanoate (Bilopaque) and sodium ipodate (Oragrafin) were studied in unanesthetized bile-fistula dogs using stepwise, increasing, intravenous infusions of the contrast materials. A constant intravenous infusion of sodium taurocholate was administered at the rate of either 0.5 or 2.0 mu moles per min per kg throughout each experiment. The biliary excretion of sodium tyropanoate or sodium ipodate was not effected by the rate of sodium taurocholate infusion. The maximum rate of biliary excretion of sodium ipodate was significantly greater than that of sodium tyropanoate with the low taurocholate infusion, but there was no significant difference between the two with the high taurocholate infusion. With the low taurocholate infusion the maximum biliary excretion rate of sodium tyropanoate (0.956 mu moles per min per kg) and sodium ipodate (1.472 mu moles per min per kg) were significantly greater than the maximum biliary excretion of iopanoic acid (Telepaque) (0.671 mu moles per min per kg). With the high taurocholate infusion the maximum biliary excretion rates of the three contrast agents were not statistically different. Both sodium tyropanoate and sodium ipodate produced an increase in canalicular bile flow (8-11 ml per millimole). These data suggest that in clinical cholecystography sodium tyropanoate and sodium ipodate are not excreted in bile more rapidly than iopanoic acid, except when the rate of biliary excretion of bile salts is low; that is, except in patients who are fasting or those who are on a fat-free diet.

The maximum biliary excretion rate of iotroxamide was found to be significantly greater than that of iodipamide in bile-fistula dogs. High bile salt excretion rates had no effect on the rate of biliary excretion of either compound, but the choleresis associated with greater bile salt excretion reduced the biliary concentration of both agents. Both are potent choleretics, stimulating about 23.5 ml of bile per mmole of contrast agent excreted in bile. This obligatory coupling of the contrast agents with water as they are excreted in bile imposes a limit on the maximum concentration that can be achieved in bile. Since iotroxamide is excreted more rapidly in bile than iodipamide for any equimolar plasma concentration, it may be a superior contrast agent for intravenous cholangiography.

The biliary excretion and choleretic effects of iodoxamate (Cholevue) and iodipamide (Cholografin) were compared in unanesthetized dogs with biliary fistulas in order to assess the potential of the two contrast agents for use in intravenous cholangiography. For any equimolar infusion rate, more iodoxamate was secreted in the bile than iodipamide was the same. At the constant basal bile flow maintained in these studies, there was no difference in the maximum biliary concentration of the two compounds. With the presently recommended doses, it is unlikely that iodoxamate will offer a striking improvement over iodipamide for intravenous cholangiography in patients with normal liver function.

(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.

Biliary tract disease is a major cause of acute pancreatitis. However, with traditionally employed Telepaque, radiographic visualization of the gallbladder during acute pancreatitis remains unreliable, even in patients with apparently normal gallbladders. Therefore, oral cholecystography has customarily been deferred for such patients for several weeks. Recently, successful oral cholecystography has been described during the acute episode of pancreatitis, using Bilopaque, a more water-soluble cholecystopaque. The relative intestinal absorption of Telepaque and Bilopaque and the ability of these agents to produce diagnostic oral cholecystograms of fasting patients with acute alcoholic pancreatitis were compared. Forty-five hospitalized patients were studied within 96 hours of admission. Mean peak plasma contrast concentrations for Bilopaque exceeded those for Telepaque. Thirty-one percent of the Bilopaque group achieved diagnostic single-dose oral cholecystograms, compared with to 11% of the Telepaque group (P less than 0.05).

The biliary excretion of two oral cholecystographic contrast agents, iocetamic acid and iopanoic acid, were compared during low and high taurocholate infusion rates. The pharmacokinetics of these compounds after intravenous infusion were studied in bile-fistula dogs using both indirect and direct pharmacokinetic techniques. The indirect multiple infusion technique, corrected for urinary excretion, provides a reliable estimate of the maximum biliary excretion rates of either contrast agent without necessitating the sampling of biliary output. The results indicate that taurocholate facilitates the biliary excretion of both agents. At both taurocholate infusion rates studied, the maximum biliary excretion rate of iocetamic acid is greater than that of iopanoic acid.

Incorporation of L-leucine-(14)C into proteins and immunoglobulins in vitro was determined in jejunal biopsy specimens from normal volunteers, patients with celiac sprue before and after introduction of gluten into the diet, patients with Whipple's disease in remission, and patients with immune deficiency states. Values for incorporation of L-leucine-(14)C into total and soluble protein by biopsies from five celiac sprue patients on a gluten-free diet were within, or slightly above, the 95% confidence limits for control data. One patient with celiac sprue and with normal intestinal histology had a normal value for incorporation into IgA; the other four patients with flat mucosas had elevated values. In Whipple's disease in remission, values for incorporation into total protein and IgA were within the control limits, whereas incorporation into soluble protein was increased. Patients with hypogammaglobulinemia or IgA deficiency had normal or elevated values for incorporation into total and soluble proteins; in these cases, however, no incorporation into IgA was detected. Biopsies from the four celiac sprue patients studied revealed that with introduction of gluten into the diet (a) incorporation into total protein, soluble protein, or both, increased; (b) incorporation into IgA increased in all patients, and in two instances the increase was greater than the increase in incorporation into total protein; and (c) incorporation into IgM increased in all patients. The changes during gluten administration usually occurred before changes in gastrointestinal absorptive function or in concentration of IgA in serum could be detected. These results indicate that gluten challenge stimulates increased local intestinal synthesis of immunoglobulins in patients with celiac sprue. The reaction occurs within days and it is possible that it plays a primary role in the pathogenesis of the disease.

We investigated the effect of pyridoxine administration in three patients with homocystinuria due to cystathionine synthase deficiency. The drug decreased the plasma concentration and urinary excretion of methionine and homocystine and the urinary excretion of homolanthionine and the homocysteine-cysteine mixed disulfide. Urinary cystine rose somewhat. Oral methionine tolerance tests before and during the patients' response to pyridoxine indicated that during response they remained deficient in their capacity to convert the sulfur of methionine to inorganic sulfate, although this capacity increased somewhat. During pyridoxine response only, the methionine loads caused increased homocystinuria. There was no indication that pyridoxine stimulated an alternate pathway of metabolism. The values for specific activity of cystathionine synthase in liver biopsy specimens from two patients in pyridoxine response were 3 and 4% of the mean control value. When these patients were not receiving pyridoxine, comparable values were 2 and 1%, respectively. The hepatic enzyme activity of the mutant patients was similar to normal enzyme activity with respect to trypsin activation, heat inactivation, and stabilization by pyridoxal phosphate. Approximate estimates were made of the relation between total body capacity to metabolize methionine and hepatic cystathionine synthase activity. These estimates suggested that because of the large normal reserve capacity of cystathionine synthase, a few per cent residual activity is sufficient to metabolize the normal dietary load of methionine. Thus, small increases in residual capacity may be of major physiological importance. However, many liver biopsies would be required to establish unequivocally that such changes were due to the administration of a particular therapeutic agent rather than to biological variation. All the data in the present study are consistent with the interpretation that pyridoxine does act by causing an increase in residual cystathionine synthase activity.