John R. Senior

The Monoglyceride Pathway of Fat Absorption in Man

The absorption of fat was studied in five male subjects with cannulation of the thoracic duct in the neck by the administration of doubly labeled monoglycerides, or triglyceride as well as labeled free glycerol or labeled free oleic acid, by gastric or duodenal intubation.Total recoveries of the administered glyceride radioactivity from the lymph lipids ranged from 35 to 53% for the glycerol label (tritium) and from 35 to 57% for the fatty acid label ((14)C). The recovery of administered radioactive free glycerol in lymph lipids was only 4.1%, even when given in mixture with bile salts, fatty acid, and monoglyceride.A comparison of the isotope ratios of the two components (glycerol and fatty acid) of the lymph glycerides with the ratios of these components of the original meal glyceride showed little change during the initial period of fat absorption, indicating that the doubly labeled monoglycerides passed into the lymph intact. During the later part of the period of major fat absorption, the ratios in lymph lipids changed due to loss of glycerol representation, indicating monoglyceride hydrolysis and portal venous diversion of free glycerol. Confirmation of the intact nature of 2-monoglyceride during absorption was made by analyzing the amount and position of the labeled fatty acid in the lymph triglycerides. The percentage of labeled fatty acid in the various positions of the lymph triglycerides was virtually identical with that of the meal during the initial period of fat absorption and then changed reflecting isomerization of fatty acids and subsequent complete hydrolysis of the glycerides.The 2-monoglyceride pathway appears to be the major route of fat absorption for man during normal digestion and absorption of dietary triglyceride.

Studies of Malabsorption Occurring in Patients with Laennec's Cirrhosis

The review of autopsy protocols and histological sections of 154 patients with Laennecs cirrhosis revealed an incidence of pancreatic lesions of 28%. A prospective study of the small bowel absorptive function of 20 alcoholic cirrhotics revealed steatorrhea in 10 of them (50%). No other parameter of small bowel absorption showed significant abnormality. Radiological studies of the intestine, Schilling tests, and small bowel biopsies were within normal limits. The D-xylose test was normal in the 20 patients as judged by normal blood levels; decreased 5-hr urinary excretion was only found in those patients with ascites or decreased renal function. Normal bacterial population was found in the duodenum of 19 of these patients. The steatorrhea found in the 10 patients could be ascribed to neomycin administration in 3 of them and to severe pancreatic insufficiency in another 4. The remaining 3 patients had maximal bicarbonate concentrations below normal levels and, therefore, probable pancreatic insufficiency. The results reveal that the steatorrhea found in these patients with Laennecs cirrhosis was secondary to either neomycin administration or pancreatic insufficiency, rather than to the cirrhotic process per se. These results indicate that small bowel absorptive function is normal in cirrhosis and that the steatorrhea commonly found in association with this disease is secondary to a variety of other disorders.

Bile salt regulation of fatty acid absorption and esterification in rat everted jejunal sacs in vitro and into thoracic duct lymph in vivo

This study was performed to investigate whether the malabsorption of fat in the blind loop syndrome is due to the presence of free bile acids or to a deficiency of conjugated bile salts produced by bacterial degradation of normal bile salts, as well as to learn something of the mechanisms by which bile salts might regulate fat absorption. In the everted gut sac of the rat in vitro, conjugated bile salts were necessary for maximal rates of fatty acid esterification to triglycerides, whereas free bile acids inhibited this process even in the presence of physiologically normal or higher concentrations of conjugated bile salts. In contrast, in the living animal the addition of similar or higher concentrations of free bile acids to infusions of fatty acids in taurocholate micellar solutions produced no reduction in the amount of fatty acid absorbed into lymph or the amount of fatty acid esterified into lymph triglyceride. Both in vitro and in the living animal, reduction in the conjugated bile salt concentration reduced both the rate of fatty acid uptake by the intestine and the esterification into triglycerides. It is concluded that the steatorrhea of the blind loop syndrome or other conditions in which upper intestinal stasis allows bacterial proliferation is not due to presence of increased gut luminal concentrations of free bile acids, but rather is a consequence of lowered concentrations of conjugated bile salts.

In vivo kinetics of radiolucent gallstone dissolution by oral dihydroxy bile acids

The rate of decrease of gallstone diameter appeared to be linear with oral bile acid treatment time, as estimated by inspection of graphic data of individual patient serial oral cholecystograms. A theoretical basis for this model was derived. The hypothesis of diameter decrease proportional to treatment time was tested with data from 223 patients with radiolucent gallbladder stones up to 20 mm in diameter treated with 7-8 or 14-15 mg.kg-1.day-1 of either ursodiol or chenodiol for 1 year, followed up after 3, 6, and 12 months of treatment. Linearity of individual sets of data points was tested by mathematical and statistical methods, including polynomial curve fitting, linear regression analysis, quadratic vs. linear analyses of covariance, and prediction of 12-month stone size by linear extrapolation from diameters at 0 and 6 months. Most patients (greater than 70%) had rates of gallstone diameter decrease that were almost linear with treatment time, independently of different dissolution rates on a given regimen. Additional treatment time needed may be estimated from cholecystograms or ultrasonograms performed before treatment and after several months.

Evaluation of corticosteroid and exchange-transfusion treatment of acute yellow-phosphorus intoxication

Abstract To evaluate steroid therapy in patients acutely intoxicated with yellow phosphorus, 49 patients were sequentially assigned to one of three groups. Group A did not receive steroids at any time, Group B received steroids from the time of admission, and steroids were used in Group C only when liver coma developed. Two out of four patients in coma recovered in Group A, none out of five in Group B, and four out of seven in Group C. Thus, steroids did not appear to prevent onset of coma in this type of liver injury and did not increase survival after development of coma. In another group of 44 patients similarly intoxicated, deep hepatic encephalopathy developed in 15. Five of these were given exchange transfusions, with two deaths and three survivals. Of the 10 not given exchange transfusions, seven died, and three survived.

Brown Bowel and Skeletal Myopathy Associated with Vitamin E Depletion in Pancreatic Insufficiency

Summary In an adult man, myopathy manifested by proximal muscle atrophy, weakness, creatinuria, and characteristic histological changes has been shown to be associated with vitamin E deficiency secondary to pancreatic disease with marked steatorrhea and with brown pigmentation of the bowel. Administration of d-α-tocopherol promptly caused disappearance of the creatinuria and resulted as well in definite but poorly understood alterations in vitamin B 12 metabolism. Among the causes of proximal muscle disease of obscure etiology, loss of fat-soluble vitamins as a result of malabsorption due to pancreatic or intestinal disorders should be considered.

Small gut mucosal activities of pyrimidine precursor enzymes in celiac disease

Summary The increased mitotic cell count in the small intestinal mucosa in celiac disease has given rise to question as to whether increased cell turnover or prolonged mitosis were occurring. Two enzymes in the pyrimidine biosynthetic pathway, aspartate carbamoyl transferase and dihydroorotate dehydrogenase, have been measured in rat and human intestinal mucosa. Activities of aspartate carbamoyl transferase in normal mucosa obtained at surgery were 247 ± 114 nmoles per g per min. No inhibition of activity of this enzyme was noted after addition of cytidine mono-, di-, or triphosphate. Dihydroorotate dehydrogenase activity was 18.1 ± 9.2 nmoles per g per min from intestinal mucosa obtained at surgery. Peroral biopsy samples from normal subjects showed aspartate carbamoyl transferase activity of 282 ± 142 nmoles and dihydroorotate dehydrogenase activity of 9.9 ± 8.6 nmoles per g per min. Mucosa obtained from patients with celiac disease snowed normal or elevated enzyme activities; the more severe lesions showed the higher levels. These results provide indirect evidence to support increased cell turnover rather than maturation arrest in mitosis in the small intestinal epithelial cells in celiac disease.