Konrad H. Soergel

Treatment of diversion colitis with short-chain-fatty acid irrigation

A condition known as diversion colitis frequently develops in segments of the colorectum after surgical diversion of the fecal stream; it persists indefinitely unless the excluded segment is reanastomosed. The disease is characterized by bleeding from inflamed colonic mucosa that mimics the bleeding of idiopathic inflammatory bowel disease, and it may culminate in stricture formation. We hypothesized that this condition is caused by the absence of luminal short-chain fatty acids, the preferred metabolic substrates of colonic epithelium. We studied four patients with diversion colitis, none of whom had evidence of Crohns, idiopathic ulcerative, or infectious colitis. The excluded segment of the rectosigmoid contained negligible concentrations of short-chain fatty acids. When D-glucose was instilled, it did not undergo appreciable anaerobic fermentation. Instillation of a solution containing short-chain fatty acids twice daily resulted in the disappearance of symptoms and the inflammatory changes observed at endoscopy, over a period of four to six weeks. Remission has been maintained for up to 14 months (in one patient) by instillation daily to twice weekly. Administering enemas containing isotonic saline, or omitting treatment for periods of two to four weeks during the regimen, by contrast, did not produce any improvement or rapid relapse of the colitis. Histologic observation revealed a distinctive type of mucosal inflammation that resolved more slowly and less completely than the gross appearance of the inflamed mucosa. From these preliminary studies we infer that diversion colitis may represent an inflammatory state resulting from a nutritional deficiency in the lumen of the colonic epithelium, which is effectively treated by local application of short-chain fatty acids, the missing nutrients.

Gastric Emptying in Patients With Diabetes Mellitus

We evaluated whether chronic nausea and vomiting in diabetic patients correlate with abnormal gastric emptying of liquid or solid, or both liquid and solid, radiolabeled meals and recorded the acute effects of metoclopramide. last, we compared several methods of analyzing gastric emptying data obtained using the gamma-camera. Eighteen healthy control subjects and 16 insulin-dependent diabetics with neuropathy were investigated. Ten of the patients suffered from chronic nausea and vomiting; the remaining 6 served as disease controls. Gastric emptying of solid and liquid meals could best be described by the slopes of two linear components and their intercept. Liquid meals generally were handled normally, while solid meals were emptied slowly by both groups of diabetics. A single dose of metoclopramide frequently corrected the delayed onset of the second, more rapidly emptying phase, that is, the major abnormality of solid emptying. The radiologic findings during a barium meal did not distinguish symptomatic from asymptomatic patients. We conclude that abnormal gastric motor function, manifested by delayed emptying of a solid meal or barium suspension, or both, is common in diabetics with neuropathy and that this motor abnormality is not the only cause of chronic vomiting. The beneficial, often short-term symptomatic effects of metoclopramide in these patients appear to be mediated by a combination of normalization of gastric emptying and a central antiemetic action.

Acid Neutralizing Capacity of Human Saliva

In this study, we evaluated the properties of human saliva relevant to its potential contribution to esophageal acid clearance. Saliva was collected by expectoration and its flow and ability to neutralize acid were assessed. In the titration of 0.1 N HCl, saliva functions as a weak base to neutralize acid. Salivas capacity for acid neutralization was defined as the quantity of 0.1 N HCl acid neutralized by 1 ml saliva. Nasoesophageal intubation, oral lozenge, and bethanechol (5 mg subcutaneously administered) increased both saliva flow and its capacity for acid neutralization. An intubated subject with a saliva flow of 1.2 mllmin produces enough saliva in 5 min to titrate 1 ml of 0.1 N HCl from a pH of 1.2 to 4.0. Atropine in a small dose of 3 μg/kg i.v. reduced saliva flow without affecting its capacity for acid neutralization, while a larger dose of 12 μ/kg i.v. abolished salivation. The capacity of saliva for acid neutralization was linearly related to its bicarbonate concentration. Bicarbonate accounted for approximately 50% of capacity for acid neutralization for resting saliva, while about 80% of the capacity for acid neutralization for lozenge-stimulated saliva was due to bicarbonate. The increase in capacity for acid neutralization for lozenge-stimulated saliva was the result of a rise in bicarbonate concentration, while the contribution of the nonbicarbonate component remained relatively constant. We conclude: (a) Saliva produced at physiologic rates and carried into the esophagus by swallowing is capable of neutralizing small amounts of intraesophageal acid within a few minutes; (b) the effect of oral lozenge, bethanechol, and atropine on salivation may explain, at least in part, why these agents alter esophageal acid clearance; (c) because intubation stimulates salivation, pH monitoring of esophageal acid clearance may underestimate the duration of acid exposure that would occur in the absence of an indwelling pH electrode; and (d) the ability of saliva to neutralize acid is due primarily to bicarbonate.

Idiopathic recurrent pancreatitis

The cause of recurrent acute pancreatitis can be identified in the majority of patients. A small group of patients in whom an etiological association is not obvious is characterized as idiopathic recurrent pancreatitis (IRP). During the last seven years, we used endoscopic retrograde cholangiopancreatography (ERCP) and sphincter of Oddi (SO) manometric pressure studies to investigate 116 patients initially diagnosed as IRP. Forty-four of the 116 patients were found to have a demonstrable cause of their pancreatitis. Appropriate therapeutic intervention was carried out in 43 of these patients with a favorable outcome in the majority of patients noted during long-term follow-up.

Sugar absorption tests, with special reference to 3-0-methyl-d-glucose and d-xylose.

Excerpt Tests employing glucose have limited value in the diagnosis of malabsorption because factors other than absorption influence glucose blood levels following an oral dose of this sugar (1). T...

Role of Endoscopic Retrograde Cholangiopancreatography in the Diagnosis and Treatment of Choledochocele

Choledochocele is a rare abnormality involving the intramural segment of the common bile duct. It may present clinically as recurrent acute pancreatitis, biliary colic, or cholestatic jaundice. A choledochocele may be easily overlooked by the conventional diagnostic methods, such as upper gastrointestinal series, intravenous cholangiogram, abdominal ultrasound, and computed tomography. Endoscopic retrograde cholangiopancreatography is helpful in demonstrating a choledochocele. Additionally, in selected cases, a choledochocele may be effectively managed by endoscopic sphincterotomy. We present the clinical, endoscopic, and radiographic findings in a series of 8 patients with choledochocele. The radiologic technique most useful in demonstrating a choledochocele at the time of endoscopic retrograde cholangiopancreatography is detailed. The pathogenesis, differential diagnosis, and relevant current literature pertaining to choledochocele are discussed.

Absorption of short-chain fatty acids from the human ileum

Acetate, propionate, andn-butyrate are the major short-chain fatty acid (SCFA) anions in the gastrointestinal tract of animal and man, accounting for 90% of total SCFA in stool water. Their absorption from the human ileum was investigated in 8 volunteer subjects by the triple-lumen perfusion technique. Each test solution contained one of the SCFAs at a concentration of 0–100 mM; sodium, potassium, and bicarbonate concentrations were kept constant, as were pH and osmolality. Absorption of each SCFA was found to be rate-limited with an apparentK′m between 22 and 27 mM and a calculatedVmax between 0.54 and 0.82 mmol/hr cm. Water, sodium, and chloride transport were not affected by substantial rates of SCFA absorption. Rather, significant stimulation of calculated bicarbonate secretion and a rise in intraluminal pH were consistently observed. The results are compatible with either of two mechanisms for SCFA absorption: an anion exchange between bicarbonate (or hydroxyl) and SCFA ions, or protonation of the SCFA anion at the mucosal surface followed by simple diffusion of nonionized SCFA into the absorbing cell.

Diabetic Diarrhea: A clinical and pathophysiological study

Thirteen patients with diabetic diarrhea were studied in order to obtain a clinical and pathophysiological description of this disorder. The patients already had debilitating complications of diabetes, such as neuropathy and occlusive vascular disease. The diarrhea was intermittent and an isolated absorption defect for fat was present in 5 of the 13 patients. Intestinal biopsies and pancreatic exocrine function were normal. No evidence was found of abnormal bacterial colonization of the upper gastrointestinal tract. Water and electrolyte absorption was normal in jejunum and ileum during continuous perfusion with normal saline. However, following the oral administration of d-xylose in water, the test meal gained in volume and its passage through the ileum was delayed. Lack of pain with jejunal distention indicated impairment of afferent sympathetic innervation. The efferent sympathetic and parasympathetic pathways appear to be intact in view of the normal response of intestinal motility to l -epinephrine, l -norepinephrine, and methacholine. These results are consistent with previously published autopsy studies showing degeneration of interneuronal pathways in the pre- and paravertebral sympathetic ganglia in diabetic diarrhea.

Multipeaked esophageal peristaltic pressure waves in patients with diabetic neuropathy

We evaluated esophageal function in 14 consecutive insulin-dependent diabetic patients who had evidence of peripheral and autonomic neuropathy, but no esophageal symptoms. One to three contraction waves immediately followed a primary peristaltic contraction wave. The majority of these multipeaked pressure complexes consisted of two peaks. Multipeaked contractions were observed with all peristaltic waves in 12 of the 14 diabetic patients and with most of the peristaltic complexes in the remaining 2 patients. Multipeaked peristaltic waves were present in 1 of 6 diabetic patients without neuropathy, in 1 of 100 consecutive nondiabetic patients referred for suspected esophageal disease, and in 1 of 10 healthy volunteers. Double-peaked peristaltic pressure complexes in the nondiabetic control subjects differed from those present in the insulin-dependent patients by their low incidence and by a tendency to be limited to the distal esophagus. Pharmacologic responses to edrophonium and atropine suggested a possible increased cholinergic tone as the basis of the multipeaked peristaltic waves in diabetics with autonomic neuropathy.

Effect of antidiuretic hormone on human small intestinal water and solute transport

The effect of i.v. Pitressin (ADH) in a dose of 1 U/hr on permeability characteristics and on absorptive capacity of the normal human small intestine was investigated. The method of continuous intestinal perfusion was employed with polyethylene glycol 4000 as a nonabsorbable marker. Unidirectional flux rates of Na and H(2)O were calculated from the disappearance of (22)Na and of (3)HOH from isotonic saline solution within the intestinal lumen. Each study consisted of two successive perfusion periods: one while the subject was hydrated, the other during ADH infusion or while the subject was dehydrated. Water and sodium absorption from isotonic NaCl occurred in the hydrated state and was abolished by ADH as well as by dehydration in the jejunum. In some instances, net gain of water and sodium in the lumen occurred. In the ileum, ADH and dehydration caused a decrease in water and sodium absorption rate. By contrast, unidirectional flux into the intestinal lumen of water and sodium, as well as dextrose and D-xylose diffusion, remained unchanged by ADH. During perfusions with hypertonic urea solutions the rates of sodium and water entry into the intestine were greatly increased during i.v. ADH infusion, whereas urea loss from the study segment remained constant. ADH in the dosage used did not affect human intestinal motility. The results suggest that circulating ADH in physiologic concentrations affects the small intestine in one of two ways: increased secretion of water and salt into the lumen or direct interference with the active sodium transport mechanism.