Pathogenesis of steatorrhea in three cases of small intestinal stasis syndrome.
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Biomedical subjects
Publications and source records attributed to D R Saunders.
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The site of synthesis and some new details of lipoprotein particle transport have been demonstrated within the jejunal mucosa of man. In normal fasting volunteers, lipoprotein particles (88%, 150-650 A diameter) were visualized within the smooth endoplasmic reticulum and Golgi cisternae of absorptive cells covering the tips of jejunal villi. Electron microscopic observations suggested that these particles exited through the sides and bases of absorptive cells by reverse pinocytosis and then passed through the extracellular matrix of the lamina propria to enter lacteal lumina. When these lipid particles were isolated from fasting intestinal biopsies by preparative ultracentrifugation, their size distribution was similar to that of very low density (S(f) 20-400) lipoprotein (VLDL) particles in plasma. After a fatty meal, jejunal absorptive cells and extracts of their homogenates contained lipid particles of VLDL-size as well as chylomicrons of various sizes. The percentage of triglyceride in isolated intestinal lipid particles increased during fat absorption. Our interpretation of these data is that chylomicrons are probably derived from intestinal lipoprotein particles by addition of triglyceride.
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The nature of the gastrointestinal absorptive defect for triglyceride in three subjects with abetalipoproteinemia has been investigated by studying peroral biopsies of the gastrointestinal mucosa. The following conclusions were reached.1) In confirmation of other studies, the abnormal vacuoles within the duodenal absorptive cells of these individuals were lipophilic.2) On chemical analysis there was significantly more mucosal lipid than found in normal fasting specimens, and almost the entire increase was due to triglyceride.3) This excess mucosal lipid was reduced by a low fat diet, but even after 34 days on such a diet there was still an excess of lipophilic material near the villus tip and increased quantities of total lipid and triglyceride when compared with material from normal subjects similarly treated.4) Although there are demonstrable qualitative changes in mucosal and plasma lipids after an acute fat load, they are not quantitatively as great as in normal individuals. Fat balance studies and the qualitative changes in plasma and tissue lipids that do occur after more extended periods on different types of dietary fat do indicate that a considerable percentage of the dietary fat is assimilated. The route by which it is absorbed remains to be clarified.
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Bisacodyl causes acute injury to the human rectal mucosa. Our objectives were to test whether pretreating the human rectum with an enema of 400 micrograms of a prostaglandin E1 analog (misoprostol) would ameliorate the mucosal injury provoked by an enema of 10 mg of bisacodyl, and to follow the evolution of the bisacodyl-induced injury in normal volunteers. Mucosal biopsies were taken 10 cm from the anus with an endoscopic forceps through a straight sigmoidoscope. Histological sections were interpreted blindly. In a preliminary experiment without bisacodyl, biopsies obtained from six subjects after misoprostol administration were indistinguishable from those taken from another six subjects after enemas of saline. In a parallel treatment experiment involving 30 subjects, all subjects sustained injury to the superficial epithelium and upper third of the crypt within 30 min after bisacodyl. Pretreatment with misoprostol also failed to prevent deeper injury to the lower third of colonic crypts. In a cross-over trial, a subset of four volunteers had biopsies at five different intervals after an enema of bisacodyl or saline. For up to 30 hours after bisacodyl, there was histological evidence of mild inflammation. Bisacodyl-induced colitis might confound the assessment of patients with suspected inflammatory bowel disease.