Farhad Navab

Intestinal absorption of two dipeptides in Hartnup disease

The results of oral tolerance tests of two dipeptides and of their constitutent amino acids are compared in normal subjects and in a case of Hartnup disease. In the control subjects the rate of absorption of phenylalanine from phenylalanyl-phenylalanine and of tryptophan from glycyl-tryptophan was slower than after the equivalent amount of the free amino acids. Absorption of the two essential amino acids (tryptophan and phenylalanine) in the patient was almost zero after administration in the free form, but was much greater after the dipeptide. Results of experiments on absorption and hydrolysis of the two peptides in the rat small intestine are also reported. It is suggested that whereas normal subjects absorb essential amino acids by a dual mechanism of mucosal uptake of free amino acids and oligopeptides, nutrition in Hartnup disease is largely dependent on uptake of oligopeptides containing the amino acids affected by the intestinal transport defect of the disease.

Studies on intestinal absorption of amino acids and a dipeptide in a case of Hartnup disease

A severely affected case of Hartnup disease is reported, where the patient responded rapidly to nicotinamide. This supports the view that all the clinical features, except reduced stature from general nutritional defect, are secondary to tryptophan and nicotinamide deficiency rather than to an unknown toxic factor. Severe malabsorption of both tryptophan and phenylalanine was demonstrated. The dipeptide carnosine was absorbed normally whereas when the two constituent amino acids, β-alanine and L-histidine, were ingested, absorption of the former was normal but that of the latter was grossly defective. The suggestion is advanced that in cases of Hartnup disease protein nutrition is maintained by intestinal uptake of amino acids as oligopeptides rather than as free amino acids. By contrast, both modes of absorption are probably important in normal subjects. Radiology of the small intestine is abnormal in Hartnup disease when a large amount of protein is admixed with the barium meal.

Intestinal absorption of carnosine and its constituent amino acids in man

Serum concentrations of β-alanine and l-histidine are compared in five normal adults after ingestion of the dipeptide carnosine (β-alanyl-l-histidine) and after equivalent amounts of the constituent free amino acids. The results indicate that absorption is significantly more rapid after the ingestion of the amino acids than after the dipeptide. The use of the test in a case of Hartnup disease suggests that carnosine is taken up by intestinal cells as the dipeptide, but subsequent hydrolysis and delivery of the constituent amino acids to the portal blood is a slower process than transport of the free amino acids themselves.

Significance of Short-segment Barrett's Esophagus

Barretts esophagus can progress to dysplasia and adenocarcinoma. Although the incidence of adenocarcinoma of the gastroesophageal junction has increased suddenly in the United States and Europe, we do not know how much of this increase is related to Barretts esophagus. Interest in mucosal cell abnormalities at the gastroesophageal junction has led researchers to re-examine short-segment Barretts esophagus. In this recently described condition, specialized columnar epithelium is found in the distal 2 to 3 cm of the esophagus, yet it is not clear how it relates to conventional long-segment Barretts esophagus, in which the metaplastic epithelium extends higher than 2 to 3 cm above the squamocolumnar junction. The reported prevalence of short-segment Barretts esophagus found on diagnostic endoscopy varies from 8% to 32%. This wide variation would be lessened by standardized location of biopsy specimens and of endoscopic and histologic staining techniques. Based on the information available, it is apparent that the age range and sex ratios are similar. Although reflux symptoms may be more common in short-segment Barretts esophagus, disturbances in esophageal motility are less severe and there is less reflux as measured by continuous pH monitoring. Furthermore, recognized complications of Barretts esophagus, such as ulceration, stricture, high-grade dysplasia, and adenocarcinoma, appear to be uncommon in short-segment Barretts esophagus.

Maintenance therapy of duodenal ulcer with famotidine: A multicenter United States study

The decision to treat a patient with duodenal ulcer should be based upon the following: severity of disease; effectiveness of treatment; and risk and cost of treatment. A number of drugs are effective for this condition. When administration of the drug is discontinued, a recurrence of the ulcer occurs most often within three months, with the rate approaching 90 percent at one year. Maintenance therapy has evolved as a method of preventing recurrence. A double-blind, randomized, multicenter study was done to compare 40 mg of famotidine at bedtime, 20 mg of famotidine at bedtime, and placebo in the maintenance treatment of patients with recently healed duodenal ulcer. In 37 centers in the United States, 303 patients received randomly allocated treatment with 40 mg of famotidine at bedtime (107 patients), 20 mg of famotidine at bedtime (97 patients), or placebo (99 patients). The treatment groups were comparable as to the risk factors and other characteristics. Esophagogastroduodenoscopies were scheduled at three, six, and 12 months of treatment. Additional endoscopies could be done at any time if symptoms suggested a relapse. Cumulative relapse rates were significantly lower in the famotidine groups than in the placebo group at all time points (p less than 0.01). The cumulative life-table relapse rates at three, six, and 12 months were 9.2, 20.9, and 24.8 percent for the 40-mg famotidine group; 13.5, 16.1, and 23.3 percent for the 20-mg famotidine group; and 39.3, 51.5, and 56.8 percent for the placebo group. No significant difference between the two famotidine groups was observed. Within each period, the relapse rate was lower with famotidine than with placebo. Famotidine is more effective than placebo as maintenance therapy. It is generally well tolerated for periods of up to one year. A dose of 20 mg at bedtime is proposed as the maintenance dose. Fewer relapses occurred in non-smokers, in females, and in patients in whom healing occurred with placebo. More relapses occurred in patients under 40 years of age, patients with a long ulcer history, or patients who were younger than 40 years of age at onset of ulcer disease.

Immunoproliferative small intestinal disease and primary small intestinal lymphoma. Relation to alpha chain protein

Forty‐three patients with immunoproliferative small intestinal disease and primary small intestinal lymphoma were studied prospectively. Eighteen patients in whom α‐chain protein was detected in the serum had significantly more features of malabsorption, and disease was localized more commonly in the jejunum. In all of these patients, a diffuse lymphoplasmacytic infiltrate was found in the intestine; in three patients lymphoma was found only in mesenteric lymph nodes. Twenty‐five patients with lymphoma in whom α‐chain protein failed to be detected had significantly more features of intestinal obstruction, and disease was found more commonly in the ileum. Five of these patients had lymphoma associated with a diffuse mucosal infiltrate that was indistinguishable from the first group. In patients available for follow‐up, no difference was found in cumulative survival over 30 months in the two groups, with approximately 40% mortality at 6 months.

Endoscopic diagnosis of eosinophilic gastritis

Eosinophilic gastritis is an unusual disease which usually is diagnosed at surgery. Here are reported 2 patients with this disease who had thick, distorted antrums at gastroscopy. Biopsy specimens were characteristic. These patients were treated without operation.

Pancreatitis and duodenitis from sarcoidosis: successful therapy with mycophenolate mofetil.

Sarcoidosis is a chronic granulomatous inflammatory disease that may affect extrapulmonary organs including the kidneys and the gastrointestinal tract (1). The most common renal complication from sarcoidosis is hypercalciuria, which may induce nephrocalcinosis and/or nephrolithiasis (2). Chronic interstitial nephritis with noncaseating granulomas in the renal interstitium may cause mild to end-stage chronic renal failure (2). In addition, glomerular lesions have been reported, including membranous nephropathy, membranoproliferative glomerulonephritis, IgA nephropathy, focal glomerulosclerosis, and rarely, crescentic gomerulonephritis (2). Therapy for glomerular diseases associated with sarcoidosis is anecdotal, and there are no data showing successful, longterm therapy for sarcoidosis associated with crescentic glomerulonephritis. The most common gastrointestinal manifestation of sarcoidosis is acute or chronic hepatitis, but disseminated gastrointestinal sarcoidosis, especially in the small intestine and pancreas, can cause considerable morbidity (1, 3–7). Glucocorticoids and/or surgery are often utilized as therapy, but the long-term outcome of patients with intestinal or pancreatic sarcoidosis has never been reported (8). We describe a patient with sarcoidosis who initially presented with idiopathic crescentic glomerulonephritis successfully treated with prednisone and cyclophosphamide. Subsequently, the patient developed pulmonary, pancreatic, and gastrointestinal sarcoidosis with a severe relapsing course despite therapy with glucocorticoids, cyclosporin, methotrexate or pentoxyphilline. The gastroin-

Early and delayed indium 111 leukocyte imaging in Crohn's disease

Twenty-seven patients with Crohns disease were studied for the presence and location of activity by both early (4 h) and delayed (18-24 h) indium 111 leukocyte imaging. The results were compared with other parameters of disease activity including Crohns disease activity index, barium studies, and endoscopy. There was a correlation between early images and Crohns disease activity index (r = 0.78) and between delayed images and index (r = 0.82). Based upon the corresponding Crohns disease activity index, the sensitivity of early and delayed imaging was 81.0% and 95.2%, respectively. Specificity of early and delayed imaging was 75.0% and 87.0%, respectively. Presence of activity on the early and delayed imaging agreed with activity on barium studies and colonoscopy in approximately 80% of cases. Correlation of location of disease by leukocyte imaging and x-ray was observed in 58.9% of early scans and 55.0% of delayed scans. Correlation of the location of disease by imaging and endoscopy was observed in 71.4% of early and 75.0% of delayed studies. Because of the possibility of occurrence of false-negative results in early images, delayed imaging should always be included in evaluation of disease activity in patients with Crohns disease who are suspected of having mild activity. Delayed imaging is not required if the early imaging study clearly shows activity.

Obstructing choledochocele: diagnosis by endoscopic ultrasound

This report demonstrates the use of endoscopic ultrasound in the diagnosis of choledochocele. The patient was an elderly female who presented with abdominal pain, weight loss, and biliary obstruction. At endoscopic ultrasound a 5 cm cystic lesion was found near the ampulla, which clearly communicated with the common bile duct.