Francis J. Tedesco

The possible role of pancreatic proteases in the turnover of intestinal brush border proteins

1. Intestinal brush border enzymes have heterogeneous rates of turnover, the largest proteins having the fastest turnover. Since the membrane faces the intestinal lumen, the effects of pancreatic factors were examined in mediating this turnover. Surgical subtotal pancreatectomy was used as an experimental model to study the turnover of brush border proteins in the absence of most pancreatic secretions. 2. Subtotal (95%) pancreatectomy of rats was found to cause elevations by about 50% of total activity and specific activities of certain brush border enzymes (maltase, sucrase, lactase), but not of others (alkaline phosphatase, trehalase). Rats were judged to be functionally deficient in pancreatic proteolytic enzymes (a) by demonstration of vitamin B-12 malabsorption, which was corrected by trypsin, and (b) by the finding of only about 20% of proteolytic activity appearing in the lumen after a test meal when compared to control. 3. To measure protein turnover in vivo the method of double labelling was used, where [3H]- and [14C]valine were administered intraduodenally in sequence 10 h apart. With this technique, a high 3H/14C ratio is correlated with rapid turnover. Proteins with apparent molecular weights of about 200 000-270 000 were found to turn over more rapidly than smaller proteins. 3H/14C ranged from 4.7 to 6.2 in animals without pancreatic insufficiency. In the face of decreased pancreatic proteolysis, the 3H/14C ratio was 2.3-3.1, similar to that of proteins with a slow half life. 4. Estimates of relative synthetic rates of large brush border proteins were lower than normal in pancreatectomized animals, but were constant over the period of the labelling experiment. The high enzyme levels in the face of lower synthetic rates confirms that, at the new steady rate, degradation rates must be slower for large brush border proteins in pancreatic insufficiency. 5. In vitro, using purified brush borders, unfractionated pancreatic enzymes were found to remove sucrase, maltase and lactase, but not alkaline phosphatase and trehalase. The enzyme most potent in this respect was the pancreatic protease, elastase. Non-proteolytic enzymes (amylase, lipase, phospholipase A) were inactive in removing enzyme from the brush border. The addition of elastase to pancreatectomized animals in vivo restored the rapid turnover rate of large brush border proteins. 6. A model is thus proposed for the normal catabolism of some large intestinal brush border proteins. It is suggested that the surface of intestinal absorptive cells is being constantly remodelled, and that certain surface enzymes are in part removed from the membrane by the action of pancreatic proteases. A possible special role for elastase is suggested.

Rectal Sparing in Antibiotic-Associated Pseudomembranous Colitis: A Prospective Study

A prospective study of 22 patients with antibiotic-associated pseudomembranous colitis demonstrated that the most distal location of the pseudomembranes was noted from 0 to 25 cm from the anus in 17 patients, from 25 to 60 cm from the anus in 3 patients, and greater than 60 cm from the anus in only 2 patients. These data suggest that the pseudomembranes will be noted by the rigid sigmoidoscope in 77% of the patients and by the flexible sigmoidoscope in 91% of the patients. Colonoscopic examination beyond 60 cm from the anus was necessary for the diagnosis of pseudomembranous colitis in 2 (9%) patients.

Diagnostic Features of Clindamycin-Associated Pseudomembranous Colitis

DIARRHEA associated with antibiotics is not an unusual finding.1 Recently, clindamycin has been reported to cause a specific type of colitis with plaque-like elevations on the colonic mucosa.2 , 3 Proctoscopy showed characteristic lesions, and x-ray findings were specific in the three patients treated with clindamycin described below. These findings should facilitate the recognition of pseudomembranous colitis from all causes, since neither of these findings is specific for clindamycin. Over a two-month period, we have seen three patients with severe diarrhea associated with clindamycin. The salient features are outlined in Table 1. Diagnostic Procedures Two tests were found of great help in diagnosing .xa0.xa0.

National ASGE survey on upper gastrointestinal bleeding: complications of endoscopy.

Data about the risks of upper endoscopy in patients with upper gastrointestinal bleeding was gathered as part of a prospective national survey of the ASGE membership. Endoscopic complications occurred in 21 of 2320 endoscopies (0.9%). These included 12 major (perforation, aspiration, bleeding) and 9 minor (mucosal tear, medication reaction, transient cardiac or pulmonary episode) complications. There were 3 deaths attributable to major complications of the procedure. These fatalities all occurred in patients with severe major underlying illnesses. Although these results indicate a higher complication rate than earlier retrospective ASGE surveys on endoscopy, they are comparable to other available data about the risks of endoscopy in the specific group of patients with upper gastrointestinal bleeding.

Upper Gastrointestinal Endoscopy in the Pediatric Patient

The value of upper gastrointestinal endoscopy in adults is well established. This study of 50 children demonstrates that upper gastrointestinal endoscopy can be performed safely and effectively in this age group without general anesthesia. Endoscopy appears more sensitive than radiology in the detection not only of superficial mucosal lesions, but of gastric and duodenal ulcers as well.

Clindamycin-associated colitis. Review of the clinical spectrum of 47 cases.

A review of 47 cases of clindamycin-associated colitis demonstrates two groups of patients. Group I includes patients who developed diarrhea and colitis while they were still receiving clindamycin and the antibiotic was immediately stopped. Group II includes patients who developed diarrhea and colitis either after a complete course of antibiotics had been given, or while they continued to receive clindamycin. It is in this latter group of patients that significant morbidity and occasional mortality occurs.

Antral diaphragm—a cause of gastric outlet obstruction in infants and children

Gastric outlet obstruction in infants and children may be due to a partial, prepyloric antral diaphragm. Twelve new patients are added to the 32 described previously. Onset of symptoms varied from shortly after birth to five years. Nonbilious vomiting was the most common presenting symptom. Radiographic evaluation requires specific technique for demonstration of the web and to differentiate this from pylorospasm and pyloric stenosis. Gastroscopy was employed in three patients. Repair usually consisted of incision of the web and construction of a patulous gastric outlet. All patients remained asymptomatic after operation. The etiology of the webs remains unknown, but they may result from an excessive local endodermal proliferation early in gastric development.

Serum Amylase Determinations and Amylase to Creatinine Clearance Ratios in Patients With Chronic Renal Insufficiency

Patients with severe chronic renal failure may have significant hyperamylasemia in the absence of clinical symptoms or signs of acute pancreatitis. Amylase to creatinine clearance (CA/CC) ratios were usually elevated in patients with chronic renal failure and were not helpful in evaluating the possibility of acute pancreatitis. The mean amylase to creatinine clearance ratio for the controls with normal renal function was 1.24 +/- 0.13. In patients with chronic renal failure, it was 3.17 +/- 0.42 (P less than 0.001). Serum amylase isoenzyme patterns revealed no difference in salivary to pancreatic isoenzyme ratios between normals (1.04 +/- 0.12) and patients with severe renal insufficiency without evidence of pancreatic disease (1.07 +/- 0.13). The isoenzymes were helpful in excluding the diagnosis of pancreatic in 1 renal failure patient whose hyperamylasemia was primarily salivary in origin and in confirming the diagnosis in another who had only a pancreatic band.

Ampicillin-associated diarrhea—A prospective study

A prospective study of 200 consecutive patients receiving ampicillin for various reasons revealed that bowel habits changed in 16% and diarrhea occurred in 4.5%. No case of pseudomembranous colitis was found. The incidence with which bowel habits changed increased with larger total doses of antibiotic. Oral and intravenous routes caused the same incidence of altered bowel habits. This study provides a proper comparison group to place clindamycin-associated colitis in proper perspective.

Pancreatic carcinoma in a patient with cystic fibrosis

Une observation dassociation rare: mucoviscidose et epithelioma glandulaire du pancreas (se manifestant par une obstruction des voies biliaires extrahepatiques) chez un homme de 42 ans