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Biomedical subjects

P M Loeb

Publications and source records attributed to P M Loeb.

27 records · Page 2Linked to original sources

Incorporation of L-leucine-14C into immunoglobulins by jejunal biopsies of patients with celiac sprue and other gastrointestinal diseases.

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.

Adult↗

Homocystinuria due to cystathionine synthase deficiency: the effect of pyridoxine.

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.

Adult↗

The biliary and urinary excretion and the choleretic effect of ioglycamide in dogs.

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.

Animals↗

The biliary and urinary excretion of sodium tyropanoate and sodium ipodate in dogs: pharmacokinetics, influence of bile salts and choleretic effects with comparison to iopanoic acid.

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.

Animals↗

Saturation kinetics of iocetamic acid: Evaluation of indirect pharmacokinetic techniques and comparison with iopanoic acid.

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.

Animals↗

Oral cholecystography in the early phase of acute alcoholic pancreatitis. A prospective, randomized comparison of Telepaque and Bilopaque.

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).

Acute Disease↗