Determinants of ileoanal pouch function.
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Biomedical subjects
Publications and source records attributed to M D Levitt.
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Although starch provides a large fraction of human caloric intake, there is limited information concerning the efficiency of intestinal absorption of this nutrient. Owing to the fermentation of starch by colonic bacteria, there is no quantitative test for starch absorption comparable to the fecal fat determination. The most accurate estimation of starch absorption has been obtained by intubating the terminal ileum and aspirating ileal contents following ingestion of a meal containing starch plus a nonabsorbable marker. Starch absorption is calculated from the ratio of starch:marker in the ileal aspirate relative to the ratio in the meal. Disadvantages of the technique are the requirement for ileal intubation and the possible adverse effect of intubation on the absorptive process. A more widely used technique to assess starch absorption involves measurement of breath hydrogen (H2) excretion after ingestion of starch. Malabsorbed starch is fermented by colonic bacteria with liberation of H2 that is absorbed and excreted in expired air. This test is simple and noninvasive and can provide quantitative measurements of starch malabsorption. Application of this technique has demonstrated that 5-10% of starch in wheat, potatoes, and corn is not absorbed by healthy subjects, while rice starch is nearly completely absorbed.
We investigated the bactericidal and bacteriostatic effects of yogurt on three strains of Escherichia coli: human toxigenic (078:H11), rabbit pathogenic (RDEC-1) and rabbit nonpathogenic [015:K14(L):H4]. Approximately 10(6) organisms were incubated in yogurt, milk, broth, and modifications of these materials. Aliquots were removed at various intervals and plated on MacConkey's agar for enumeration of E. coli. Yogurt was bactericidal (at least 5 log10 reduction in bacterial counts) to all three strains of E. coli with less than 10 CFU/ml remaining by 9 hr. In contrast, all three strains replicated rapidly in milk and broth, reaching maximum concentrations by 9 hr. The E. coli strains survived and multiplied in milk acidified to the same pH as the yogurt. Yogurt (native pH 4.1-4.4) in which the pH was brought up to and maintained at pH 5.5 or pH 7 for 8 hr was not bactericidal to E. coli. Heat-treated yogurt and the filtered supernatant of centrifuged yogurt (both containing no yogurt bacteria) were only bacteriostatic. We conclude that both live yogurt bacteria and a pH near 4.5 are necessary for the bactericidal activity of yogurt. The possibility that yogurt ingestion could protect against infection via other foods contaminated with pathogenic E. coli merits further in vivo investigation.
The resistance to absorption resulting from poor stirring of luminal contents (RLum) is considered to be equivalent to an unstirred layer of greater than 600 microns in the human small intestine. We measured RLum in the jejunum of conscious dogs by assessing the absorption rate of two rapidly absorbed probes, glucose, and [14C]warfarin. When RLum was expressed as an unstirred layer, the maximal thickness of the unstirred layer (assuming negligible epithelial cell resistance) was only approximately 35 and 50 microns for perfusion rates of 26 and 5 ml/min, respectively. Maximal unstirred layer thickness for the human jejunum, calculated from previous studies of glucose absorption, yielded a mean value of only 40 microns (range: 23 to 65 microns). Since epithelial resistance appears to be negligible during absorption of low concentrations of glucose, the maximal unstirred layer of 40 microns should be close to the true value for glucose in the human small intestine. We conclude that the unstirred layer for rapidly absorbed compounds in dogs and man are less than one-tenth of previously reported values, but this layer still may remain the rate limiting step in absorption of rapidly transported compounds.
During a 6 month period in 1988 five women were treated at Colchester General Hospital for carcinoma of the rectum, each more than 10 years after undergoing pelvic irradiation. Although irradiation has not been proven to induce human colorectal cancer, considerable circumstantial and experimental evidence supports this belief. Features suggestive of radiation-induced colorectal cancer are the presence of radiation-damaged bowel adjacent to the carcinoma and a mucus-secreting ('colloid') histological pattern. The increasing number of women being exposed to rectal irradiation in the course of treatment of gynaecological malignancy may result in an increase in the incidence of radiation-induced rectal cancer. Awareness of this potential long-term complication is important when planning follow-up of patients subjected to pelvic radiotherapy.
The serum amylase concentration reflects the balance between the rates of amylase entry into and removal from the blood. Hyperamylasemia can result either from an increased rate of entry of amylase into the circulation and/or a decreased metabolic clearance of this enzyme. The pancreas and salivary glands have amylase concentrations that are several orders of magnitude greater than that of any other normal tissue, and these two organs probably account for almost all of the serum amylase activity in normal persons. A variety of techniques are now available to distinguish pancreatic from salivary-type isoamylase. Pancreatic hyperamylasemia results from an insult to the pancreas, ranging from trivial (cannulation of the pancreatic duct) to severe (pancreatitis). In addition, loss of bowel integrity (infarction or perforation) causes pancreatic hyperamylasemia due to absorption of amylase from the intestinal lumen. Hyperamylasemia due to salivary-type isoamylase is observed in conditions involving the salivary glands. In addition, this type of hyperamylasemia occurs in conditions in which there is no clinical evidence of salivary gland disease, such as chronic alcoholism, postoperative states (particularly postcoronary bypass), lactic acidosis, anorexia nervosa or bulimia, and malignant neoplasms that secrete amylase. Hyperamylasemia can also result from decreased metabolic clearance of amylase due to renal failure or macroamylasemia (a condition in which an abnormally high-molecular-weight amylase is present in the serum). Patients with abdominal pain and a markedly elevated serum amylase (more than three times the upper limit of normal) usually have acute pancreatitis, and additional serum enzyme testing is not helpful. Patients with smaller elevations of serum amylase often have conditions other than pancreatitis, and measurement of a serum enzyme more specific for the pancreas (pancreatitic isoamylase, lipase or trypsin) is frequently of diagnostic value in such patients.
To study the fate of oleate in the colon, oleate labeled with carbon 14 was instilled into the cecum of four rats through chronically implanted cecal cannulas. Fecal recovery of 14C and 14CO2 excretion were measured over a 3-day period. A mean of only 57% +/- 6% of the dose of [14C(U)]oleate was recovered as 14C in fecal lipid. About 8% was recovered in the aqueous phase of feces and 4% was recovered as 14CO2. Occlusion of the terminal ileum did not diminish 14CO2 excretion, excluding ileal reflux with small bowel absorption. Studies in two germ-free rats showed no conversion of [14C(U)]oleate to fecal water-soluble compounds, indicating that [14C]oleate is converted into water-soluble compounds by bacterial metabolism. The metabolism of [14C]oleate to 14CO2 was also observed in germ-free rats, indicating oxidation in the colon or other host tissues. We conclude that the colonic absorption of lipid or lipid metabolites plus conversion to water-soluble fecal compounds or volatile metabolites results in a fecal fat measurement that appreciably overestimates small bowel absorption of lipid.
Previous studies of the influence of increased luminal viscosity on intestinal absorption have yielded conflicting results ranging from no effect to a marked diminution. We measured the absorption of three probes (carbon monoxide, [14C]warfarin, 5.5 mM glucose) from a saline infusate or from saline containing 0.6% guar, which yielded a 20-fold increase in viscosity. Two animal models were used: (a) conscious nonlaparotomized rats with chronically implanted cannulas and (b) anesthetized laparotomized rats. In the anesthetized laparotomized rats, absorption was independent of perfusate viscosity. In the conscious nonlaparotomized rats, the absorption of each of the three probes was significantly greater than in the anesthetized laparotomized rats and increased viscosity caused a 60%-70% decrease in the clearance of the three probes. In anesthetized laparotomized rats, we have shown that fluid moves with laminar flow, and increased infusate viscosity cannot further reduce luminal stirring (or absorption). In conscious, nonlaparotomized rats, laminar flow is disrupted by normal gut motility causing better luminal stirring. Such stirring is inhibited by a viscous infusate resulting in decreased absorption. We conclude that the conflicting results seen in previous studies can be attributed to the model used. In conscious animals where luminal stirring was good, a viscous infusate caused decreased absorption.
To determine the role played by stagnant peritoneal fluid layers in the diffusion of solutes between peritoneal cavity and blood, we measured peritoneal transfer of urea, creatinine, [14C]-L-glucose and protein in anesthetized rats shaken at varying rates on an orbital platform shaker. The diffusion transfer rates of the low molecular weight solutes increased dramatically with shaking, with near maximal values obtained at a shaking rate of 250 RPM. The permeability area product (PA) for each of the low molecular weight solutes increased about fourfold with rapid shaking while the PA of protein increased by only about 50%. It seems likely while the PA of protein increased by only about 50%. It seems likely that shaking increased PA primarily via reduction of the thickness of stagnant peritoneal fluid layers, although increases in surface area or changes in tissue permeability cannot be excluded with certainty. We conclude that stagnant fluid layers probably are the rate limiting step in diffusive peritoneal transfer of low molecular weight solutes in stationary rats.
We evaluated the effect of high-fiber cereals on short-term food intake. At 0730, 14 subjects ingested one of five cereals, plus milk and orange juice. At 1100 they were presented with a buffet lunch. There was a significant inverse correlation between fiber content of the cereals and energy intake at lunch. In a second study subjects ingested a very-high-fiber (VHF) cereal or a very-low-fiber (VLF) cereal. Fewer kcalories were ingested at lunch after ingestion of the VHF cereal than after ingestion of the VLF cereal. The degree of colonic microbial fermentation of the various cereals was evaluated by breath-hydrogen analysis. The higher-fiber cereals resulted in greater hydrogen production; however, this may not influence energy intake. The results of questionnaires that asked about hunger indicated that food intake can be reduced without the perception of feeling less hungry. Thus, we found that cereals containing relatively large quantities of dietary fiber may decrease short-term food intake.
Three case reports of cyclical rectal bleeding in endometriosis affecting rectum and sigmoid colon emphasize the close relationship between such cyclical bleeding and intestinal endometriosis. The cause of bleeding, however, is still unclear. The predilection of endometriotic deposits for the outer layers of the bowel wall suggests that mucosal involvement is not a prerequisite for rectal bleeding. The frequent absence of identifiable intramural haemorrhage casts doubt on the premise that intestinal endometriotic deposits 'menstruate'. The cause may simply be a transient tear in normal mucosa due to swelling of an underlying endometriotic deposit at the time of menstruation.
In this article, the authors describe the various subgroups of pancreatitis and discuss pathophysiologic etiologies as they are currently understood. They present their opinions as to the relative usefulness of various biochemical tests for acute pancreatitis. They discuss their approach to the differential diagnosis of abdominal pain. They also describe clinical circumstances, such as renal failure, for which accurate diagnosis of pancreatitis is more difficult than usual.
Virtually all CO production in humans and animals is thought to result from the catabolism of heme, and endogenous CO production (VCO) is used as a measure of heme turnover. Using a rebreathing technique, we found that previously fed mice had an apparent VCO that was 40% greater than that of mice that had been fasted before the study. This unexpected result was shown to reflect an excess CO production by the excreta (feces, urine, or both) of fed mice relative to the excreta of fasted mice. Incubation of feces and urine of humans, rats, and mice demonstrated CO release that was not inhibited by autoclaving or acidification to pH 1. CO release from excreta was markedly reduced, however, under anaerobic conditions, and fed and fasted animals excreted CO at the same rate when their excreta were maintained in an anaerobic state. We conclude that feces and urine can release CO via nonenzymatic, oxidative reactions and, under some circumstances, this source of CO can influence measurements of VCO.
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Breath hydrogen tests are limited by leak of gases from breath samples from standard glass or plastic syringes. These losses may be substantial when these samples are stored for long periods of time. We describe a simple manipulation involving the use of a mineral oil or water seal at the end of the syringe barrel that markedly reduces the leakage of H2 and other gases to negligible levels.
A 71-yr-old woman with a widely metastatic lipid-rich variant of breast cancer was found to have striking hyperamylasemia (85-fold normal). By isoelectric focusing, agarose gel electrophoresis, and a wheat protein inhibitor assay, the predominant serum amylase appeared to be identical to pancreatic isoamylase. Serum trypsin, serum lipase, and an abdominal computed tomography scan were normal, excluding the possibility of pancreatitis. Furthermore, both the primary breast tumor and skin metastases that developed 10 yr later stained immunohistochemically for amylase. Thus, breast carcinoma must be added to the list of tumors causing ectopic hyperamylasemia, and this case shows that nonpancreatic malignancies may produce pancreatic-type hyperamylasemia.
A case of inflammatory pseudotumour of the liver is described, the twelfth such case reported. Although these lesions are benign and self-limiting, they may encroach upon the biliary tree or portal vein and may be confused with true hepatic neoplasia. In the presence of single or multiple hepatic deposits seen on radiologic examination, a history of fever (or other systemic symptoms) and a negative fine needle aspiration biopsy should raise the possibility of inflammatory pseudotumour and prompt formal biopsy to guide further treatment.
Twenty four patients with malignant bile duct obstruction were treated with intraluminal radiotherapy using iridium-192 wire inserted through an endoscopically placed nasobiliary catheter. Biliary drainage after treatment was maintained by an endoprosthesis. The median dose of intraluminal radiotherapy was 6000 cGy; two patients with cholangiocarcinoma were given a second course because of disease extension; four patients with pancreatic carcinoma received additional external irradiation (3000 cGy). There was one early death from a cerebrovascular accident (30 day mortality, 4.2%). Cholangitis (30%) was the major early complication and stent blockage (40%) the major late complication; there were no complications directly attributable to radiotherapy. The median survival for patients with pancreatic carcinoma was 250 days and for cholangiocarcinoma, 300 days. This method is technically feasible and may prove safer than the transhepatic technique. The ability of intraluminal irradiation to improve palliation or lengthen survival in patients with malignant bile duct obstruction remains uncertain. Assessment by a prospective, controlled trial is essential.