Ivan T. Beck

Villous damage induced by suction biopsy and by acute ethanol intake in normal human small intestine

Previous studies by us indicated that ethanol in concentrations of 2.0–4.8% produced subepithelial blebs in the jejunum of the hamster. In the rat, due to rupture of the blebs, there was denudation of the villus tip epithelium. There are no similar data on humans. Ethanol, in quantities equivalent to 4.8–6.4 ounces of 80 proof whiskey (diluted to 20% w/v), was infused into stomachs of 20 normal human volunteers. Subjects were divided into groups (Gr) according to the amount or type of alcohol given, and the site of biopsies (SB). Gr 1∶60 g ethanol, SB=jejunum. Gr 2∶45 g ethanol, SB=jejunum. Gr 3∶45 g ethanol, SB=duodenum. Gr 4∶45 g ethanol as 4.8 oz 80 proof whiskey, SB=duodenum. To compare the morphology in the absence and presence of ethanol, biopsies were obtained from each volunteer before ethanol administration (control period). immediately after peak ethanol concentration in the duodenum or jejunum (ethanol period), and when intraluminal ethanol concentration fell towards zero (recovery period). The mean peak intraluminal ethanol concentrations in the four groups varied between 5.69% and 9.37% (w/v). Ethanol-induced damage was evaluated using strict preset criteria. Coded slides were evaluated by two observers. Suction biopsy damaged 18% of the villi even in biopsies obtained during the control period. Ethanol produced a statistically significant increase in the number of damaged villi (mean of all groups 45%, range∶32% in Gr 2 to 62% in Gr 3). During the recovery period the number of damaged villi fell to that seen in control period biopsies. Ethanol, in quantities equivalent to those ingested during moderate drinking, may produce transient damage to the upper small intestine of man. Conversely, ethanol may simply increase the susceptibility of the mucosa to the unavoidable trauma of suction biopsy. However, the histological and ultrastructural changes were similar to those induced by ethanol in small laboratory animals.

Ambulatory esophageal manometry, pH-metry, and holter ECG monitoring in patients with atypical chest pain

Standard Holter electrocardiographic (ECG) monitoring was combined with ambulatory esophageal manometry and pH-metry in 25 patients with atypical chest pain in order to determine whether an association could be found between spontaneous pain episodes and ischemic ECG changes or esophageal dysfunction. Results of ambulatory testing were compared to those obtained with standard esophaeal manometry and provocative testing. Twenty-two of the 25 patients experienced a total of 88 pain episodes during ambulatory testing. Although 15 of the 22 patients (68%) experiencing pain during testing had at least one pain episode that corelated temporally with gastroesophageal reflux, esophageal dysmotility or ischemic ECG changes, 65% of all pain episodes were unrelated to abnormal esophageal events or ECG changes. Seventeen percent of pain episodes were associated with gastroesophageal reflux, 15% with esophageal dysmotility,and 2% with a combined acid reflux and esophageal dysmotility event. Only one pain episode was associated with ischemic ECG changes. Twelve of the 15 patients with chest pain episodes associated with reflux or esophageal dysmotility had othe identical pain episodes in which there was no correlation. Reproduction of a patients pain during standard manometry with provocative testing did not predict a strong correlation between the patients spontaneous pain episodes and esophageal dysfunction during ambulatory recordings. In summary, patients with atypical chest pain have relatively few spontaneous pain episodes that correlate with gastroesophageal reflux, esophageal dysmotility, or ischemic ECG changes. It appears that different stimuli can trigger identical episodes of chest pain, which suggests that many of these patients may have dysfunction of their visceral pain sensory mechanisms.

The Role of Pancreatic Enzymes in the Pathogenesis of Acute Pancreatitis: III. Comparison of the pathologic and biochemical changes in the canine pancreas to intraductal injection with bile and with trypsin

Summary Acute pancreatitis was induced by intraductal injection of bile or of trypsin into the pancreases of dogs. The histologic pattern resulting from the 2 different agents was dissimilar. In bile-induced pancreatitis the first change was a coagulation necrosis of the cells of a part of the lobule. In trypsin-induced pancreatitis, the earliest response was a marked hyperemia with vasodilation of the capillaries. Only later on did liquefaction necrosis of the cells occur. In both types, with the passage of time, secondary inflammatory changes with fatty necrosis were superimposed. Biochemically, these 2 types of pancreatitis were also different. In bile-induced pancreatitis proteolytic enzyme activity could not be recovered from the pancreatic tissue up to 1 hour after injection. In the pancreatic tissue of dogs in which pancreatitis was induced by trypsin, free proteolytic enzyme acttvity was present in the early stages of the disease. The data suggest different mechanisms for bile and for trypsin in the production of acute pancreatitis.

A syndrome of acute self-limiting ulcerative esophagitis in young adults probably due to herpes simplex virus.

Five healthy young adults developed an acute self-limiting ulcerative esophagitis. Two had definite evidence of herpes virus being present and a third one had appropriate changes in herpes simplex viral titer. All cases followed a characteristic and similar course consisting of sudden onset of odynophagia, multiple discrete small ulcers in the esophagus and herpetiform lesions elsewhere in the skin or mouth. Although most previous reports of herpes esophagitis indicate that it is an “opportunistic” infection in debilitated hosts, the present report indicates that this infection, in patients who are otherwise well, may occur more frequently than one would have previously suspected. Therefore herpes simplex virus should be considered as a possible etiological agent in the differential diagnosis in patients presenting with a sudden onset of odynophagia.

Effect of ethanol on glucose and water absorption in hamster jejunumin vivo methodological problems: Anesthesia, nonabsorbable markers, and osmotic effect

We studied the effect of ethanol on glucose and water absorptionin vivo. In preliminary experiments, using sodium amytal anesthesia, we found that control animals, whose jejunal segment was perfused without ethanol, required more anesthetic agent than those perfused with ethanol. Thus, to allow for unbiased comparison of the absorption data between the two groups of animals, all absorption studies were carried out on conscious restrained hamsters. We found that ethanol did not influence the permeability of the jejunum to polyethylene glycol (PEG) and meglumine diatrizoate. In addition, ethanol did not influence the time required for the onset of steady-state absorption. Using both the gravimetric and the electrical methods, we were unable to show any measurable osmotic pressure exerted by ethanol (150–1050 mM) on the hamster jejunum. In the absorption studies we found that perfusion of the hamster jejunum with five increasing concentrations of ethanol (450–1050 mM) appeared to cause a concentration-dependent depression in steady-state glucose transport. Water transport was depressed only when 4.8% (1050 mM) ethanol was perfused.

Indium-111-labeled autologous leukocyte imaging and fecal excretion. Comparison with conventional methods of assessment of inflammatory bowel disease.

This study was designed to evaluate the role of111In-labeled leukocyte imaging and fecal excretion in the assessment of inflammatory bowel disease. We compared these tests to various indices of disease activity in Crohns disease, to Trueloves grading in ulcerative colitis, and to endoscopy, x-ray, and pathology in both diseases. Eleven controls, 16 patients with Crohns disease, 13 with ulcerative colitis, and 3 with other types of acute bowel inflammation were studied (positive controls). Indium scanning was performed at 1,4, and 24 hr. Fourteen of 16 patients with active Crohns disease had positive scans but in only five was localization accurate. One patient had inactive ulcerative colitis, and the scan was negative. Of 12 patients with active ulcerative colitis, 10 had positive scans but disease localization was accurate in only four. Disease extent was correctly defined in 1 of the 3 Positive Controls. There was no significant difference in the accuracy of scanning at 1,4 or 24 hr.111In fecal excretion was significantly higher in patients with inflammatory bowel disease than in controls, and there was correlation between111In fecal excretion and most of the indices of disease activity in Crohns disease. In ulcerative colitis,111In fecal excretion did not correlate with Trueloves grading but reflected colonoscopic assessment of severity. In conclusion,111In-labeled leukocyte scanning lacks sensitivity with respect to disease extent, but fecal excretion of111In correlates well with disease severity as determined by other methods.

Laboratory assessment of inflammatory bowel disease.

Presently there are no specific laboratory tests to diagnose inflammatory bowel disease (IBD). Nonspecific tests to differentiate diarrhea due to mucosal injury from that occurring in patients with normal bowel mucosa (eg, fecal occult blood, leukocytes, etc) are not helpful. Tests to exclude infectious agents are very important, since the clinical and radiological appearance of these may mimic IBD, and patients with IBD may suffer from superinfection. There are no laboratory tests which can differentiate Crohns colitis from ulcerative colitis (UC). The tests used in the assessment and management of severely ill patients (Hgb, WBC, electrolytes, etc) are important, since abnormalities need to be corrected on an ongoing basis. The tests used to assess nutritional status are of little clinical value, since “clinical assessment” is as good as the laboratory assessment. Estimation of disease activity by tests is rarely better than the juudgment of the clinician. Workup for malabsorption in Crohns disease and the assessment of absorptive capacity of the terminal ileum are important for proper planning of management. Laboratory tests are also useful in clarifying the nature of some complications (eg, anemias and joint diseases).Presently there are no specific laboratory tests to diagnose inflammatory bowel disease (IBD). Nonspecific tests to differentiate diarrhea due to mucosal injury from that occurring in patients with normal bowel mucosa (eg, fecal occult blood, leukocytes, etc) are not helpful. Tests to exclude infectious agents are very important, since the clinical and radiological appearance of these may mimic IBD, and patients with IBD may suffer from superinfection. There are no laboratory tests which can differentiate Crohns colitis from ulcerative colitis (UC). The tests used in the assessment and management of severely ill patients (Hgb, WBC, electrolytes, etc) are important, since abnormalities need to be corrected on an ongoing basis. The tests used to assess nutritional status are of little clinical value, since “clinical assessment” is as good as the laboratory assessment. Estimation of disease activity by tests is rarely better than the juudgment of the clinician. Workup for malabsorption in Crohns disease and the assessment of absorptive capacity of the terminal ileum are important for proper planning of management. Laboratory tests are also useful in clarifying the nature of some complications (eg, anemias and joint diseases).

Effect of ethanol on the morphology of hamster jejunum

In order to study the morphological effects of exposure of the jejunum to low ethanol concentrations, we perfused hamster jejunum with 2.1–4.8% ethanol. Following 45 min exposure, many of the villi developed fluid-filled blisters. To compare these findings to the effect of an inert solute at similar concentrations, we perfused hamster jejuna with mannitol. This caused necrosis of the villus tips but no blister formation. Therefore the blisters were the result of the action of ethanol. The rat jejunum was less resistant to ethanol than that of the hamster. We suggest that the initial insult of the freely permeant ethanol is deep to the epithelium, resulting in accumulation of edema under the epithelium.

Effect of Ethanol on jejunal Regional Blood Flow in the Rabbit

The effects of intraluminal ethanol perfusion (3.0% and 6.0% vt/vol) on mucosal morphology, water transport, and regional blood flow were examined in in vivo jejunal segments of pentobarbital-anesthetized rabbits. Compared with control segments, ethanol-perfused segments exhibited morphological alterations of the mucosa consisting of subepithelial fluid accumulation (bleb formation), exfoliation of enterocytes, and vascular congestion. The prevalence of epithelial damage was significantly increased in the segments perfused with 6% ethanol. Net water transport was significant (p less than 0.025) depressed in segments perfused with 3.0% and 6.0% wt/vol ethanol. In animals in which the control segment was absorbing water, ethanol led to a depression in net water absorption or to the reversal of absorption to net secretion. In animals in which the control segment exhibited secretion, ethanol led to an enhanced net secretion. Blood flow through the total jejunal wall and through the luminal layer (consisting of mucosa plus submucosa) was significantly (p less than 0.05) increased by the presence of 3.0% and 6.0% wt/vol ethanol in the intestinal lumen. Blood flow in the external layer of the jejunum (consisting of muscularis plus serosa) did not change significantly. It therefore appears that the ethanol-induced alterations in jejunal mucosal morphology and water transport are accompanied by a localized mucosal or submucosal hyperemia, or both. However, a direct cause and effect relationship between these remains to be established.

Ethanol-induced inhibition of glucose transport across the isolated brush-border membrane of hamster jejunum

Acute exposure of jejunal mucosa to ethanol has been reported to produce a depression of transmural glucose transport across this organin vitro andin vivo. In an attempt to understand the mechanism of action of ethanol on intestinal transport, in the present study we have investigated the effect of ethanol on glucose uptake by purified brush-border membrane vesicles of hamster jejunum. Ethanol, in concentrations found in man after moderate drinking (1–5% w/v), was found to depress glucose uptake by the brush-border membrane in a dose-dependent and time-dependent manner. Mannose was used to measure nonspecific uptake, and we found that the ethanol-induced depression of glucose uptake was not related to an alteration of the nonspecific uptake of this sugar. The inhibition of glucose uptake of the ethanol-treated membranes completely disappeared after repeated washing of the membranes with ethanol-free buffer. Accordingly, the ethanol-induced depression of glucose uptake was not the result of irreversible damage to membrane proteins but was related to a direct effect of ethanol on the brush-border membrane. On the basis of these findings, it is concluded that a direct interference with glucose translocation across the brush border plays an important role in the ethanol-induced depression of transmural jejunal glucose absorption.