Michael E. Presti

Repetitive Self-Limited Acute Pancreatitis Induces Pancreatic Fibrogenesis in the Mouse

The role of repetitive acute injury in the pathogenesis of chronic pancreatitis remains unknown. To determine if repetitive injury induced by pancreatic hyperstimulation would reproduce the characteristic features of human chronic pancreatitis, acute reversible pancreatic injury was induced in mice by twice weekly cerulein treatment, 50 μg/kg/hr × 6 hr, for 10 weeks. Procollagen α1(I) mRNA was markedly increased by week 2. Sirius red staining of interstitial collagen demonstrated progressive accumulation of extracellular matrix surrounding acinar units and in interlobular spaces. Atrophy, transdifferentiation of acinar units to ductlike tubular complexes, and dilatation of intraacinar lumina also developed. Electron microscopy demonstrated the presence of stromal cells in areas of fibrosis with morphologic characteristics of pancreatic stellate cells. These findings demonstrate that, in a murine model, repetitive acute injury to the pancreas by hyperstimulation can reproduce the major morphological characteristics of human chronic pancreatitis.

Cholecystectomy is an effective treatment for biliary dyskinesia

BACKGROUND An increasing number of reports indicate symptomatic relief of biliary colic symptoms after cholecystectomy for biliary dyskinesia. Despite this, cholecystectomy as a treatment for biliary dyskinesia remains controversial. Our aim was to determine efficacy of cholecystectomy in alleviating biliary dyskinesia symptoms and the correlation with histologic findings. METHODS Records of patients with gallbladder ejection fraction <35% between January 1994 and February 1999 were reviewed. Gallbladder pathology and degree of symptomatic improvement were determined on follow-up. RESULTS Of the 27 cholecystectomy patients, 24 (89%) had significant improvement, 2 (7%) had partial improvement, and 1 (4%) had minimal improvement. Ten patients (43%) had normal gall-bladder, and 9 (90%) of them had significant improvement after cholecystectomy. Of the 6 nonsurgical patients, none had significant improvement, 4 (67%) had partial improvement, and 2 (33%) had minimal improvement. CONCLUSIONS Biliary dyskinesia patients who underwent cholecystectomy had significantly greater symptom improvement compared with nonsurgical patients. Pathologic correlation suggests chronic inflammation may not be the only cause of gallbladder dysfunction. Cholecystectomy should be a first-line therapy for biliary dyskinesia patients.

Role of Mycobacterium paratuberculosis in Crohn's disease: a prospective, controlled study using polymerase chain reaction.

PURPOSE:Mycobacterium paratuberculosis has been proposed as a causative agent in patients with Crohns disease. The purpose of this study was to determine whetherM. paratuberculosis was present in tissue from patients with Crohns disease in a defined geographic area. METHODS: We prospectively evaluated, using polymerase chain reaction and culture, whetherM. paratuberculosis was present in 44 specimens (37 from intestinal mucosal biopsies and 7 from surgical resections) from patients with Crohns disease, ulcerative colitis, or normal colonic mucosa. RESULTS: Of the 25 specimens tested from the 21 Crohns patients, only 1 positive specimen was noted, whereas the 8 specimens from the 5 ulcerative colitis patients and the 11 specimens from the 11 control patients failed to demonstrate a positive result with polymerase chain reaction. Cultures of all specimens revealed no growth ofM. paratuberculosis. CONCLUSION:M. paratuberculosis was only rarely detected in biopsy or surgical specimens from patients with Crohns disease. These results do not support a common causative role ofM. paratuberculosis in Crohns disease.PURPOSE: Mycobacterium paratuberculosis has been proposed as a causative agent in patients with Crohns disease. The purpose of this study was to determine whether M. paratuberculosis was present in tissue from patients with Crohns disease in a defined geographic area. METHODS: We prospectively evaluated, using polymerase chain reaction and culture, whether M. paratuberculosis was present in 44 specimens (37 from intestinal mucosal biopsies and 7 from surgical resections) from patients with Crohns disease, ulcerative colitis, or normal colonic mucosa. RESULTS: Of the 25 specimens tested from the 21 Crohns patients, only 1 positive specimen was noted, whereas the 8 specimens from the 5 ulcerative colitis patients and the 11 specimens from the 11 control patients failed to demonstrate a positive result with polymerase chain reaction. Cultures of all specimens revealed no growth of M. paratuberculosis. CONCLUSION: M. paratuberculosis was only rarely detected in biopsy or surgical specimens from patients with Crohns disease. These results do not support a common causative role of M. paratuberculosis in Crohns disease.PURPOSE: Mycobacterium paratuberculosis has been proposed as a causative agent in patients with Crohns disease. The purpose of this study was to determine whether M. paratuberculosis was present in tissue from patients with Crohns disease in a defined geographic area. METHODS: We prospectively evaluated, using polymerase chain reaction and culture, whether M. paratuberculosis was present in 44 specimens (37 from intestinal mucosal biopsies and 7 from surgical resections) from patients with Crohns disease, ulcerative colitis, or normal colonic mucosa. RESULTS: Of the 25 specimens tested from the 21 Crohns patients, only 1 positive specimen was noted, whereas the 8 specimens from the 5 ulcerative colitis patients and the 11 specimens from the 11 control patients failed to demonstrate a positive result with polymerase chain reaction. Cultures of all specimens revealed no growth of M. paratuberculosis. CONCLUSION: M. paratuberculosis was only rarely detected in biopsy or surgical specimens from patients with Crohns disease. These results do not support a common causative role of M. paratuberculosis in Crohns disease.

Role ofMycobacterium paratuberculosis in Crohn's disease

PURPOSE:Mycobacterium paratuberculosis has been proposed as a causative agent in patients with Crohns disease. The purpose of this study was to determine whetherM. paratuberculosis was present in tissue from patients with Crohns disease in a defined geographic area. METHODS: We prospectively evaluated, using polymerase chain reaction and culture, whetherM. paratuberculosis was present in 44 specimens (37 from intestinal mucosal biopsies and 7 from surgical resections) from patients with Crohns disease, ulcerative colitis, or normal colonic mucosa. RESULTS: Of the 25 specimens tested from the 21 Crohns patients, only 1 positive specimen was noted, whereas the 8 specimens from the 5 ulcerative colitis patients and the 11 specimens from the 11 control patients failed to demonstrate a positive result with polymerase chain reaction. Cultures of all specimens revealed no growth ofM. paratuberculosis. CONCLUSION:M. paratuberculosis was only rarely detected in biopsy or surgical specimens from patients with Crohns disease. These results do not support a common causative role ofM. paratuberculosis in Crohns disease.PURPOSE: Mycobacterium paratuberculosis has been proposed as a causative agent in patients with Crohns disease. The purpose of this study was to determine whether M. paratuberculosis was present in tissue from patients with Crohns disease in a defined geographic area. METHODS: We prospectively evaluated, using polymerase chain reaction and culture, whether M. paratuberculosis was present in 44 specimens (37 from intestinal mucosal biopsies and 7 from surgical resections) from patients with Crohns disease, ulcerative colitis, or normal colonic mucosa. RESULTS: Of the 25 specimens tested from the 21 Crohns patients, only 1 positive specimen was noted, whereas the 8 specimens from the 5 ulcerative colitis patients and the 11 specimens from the 11 control patients failed to demonstrate a positive result with polymerase chain reaction. Cultures of all specimens revealed no growth of M. paratuberculosis. CONCLUSION: M. paratuberculosis was only rarely detected in biopsy or surgical specimens from patients with Crohns disease. These results do not support a common causative role of M. paratuberculosis in Crohns disease.PURPOSE: Mycobacterium paratuberculosis has been proposed as a causative agent in patients with Crohns disease. The purpose of this study was to determine whether M. paratuberculosis was present in tissue from patients with Crohns disease in a defined geographic area. METHODS: We prospectively evaluated, using polymerase chain reaction and culture, whether M. paratuberculosis was present in 44 specimens (37 from intestinal mucosal biopsies and 7 from surgical resections) from patients with Crohns disease, ulcerative colitis, or normal colonic mucosa. RESULTS: Of the 25 specimens tested from the 21 Crohns patients, only 1 positive specimen was noted, whereas the 8 specimens from the 5 ulcerative colitis patients and the 11 specimens from the 11 control patients failed to demonstrate a positive result with polymerase chain reaction. Cultures of all specimens revealed no growth of M. paratuberculosis. CONCLUSION: M. paratuberculosis was only rarely detected in biopsy or surgical specimens from patients with Crohns disease. These results do not support a common causative role of M. paratuberculosis in Crohns disease.

Persistent Clostridium difficile colitis : A possible etiology for the development of collagenous colitis

Collagenous colitis is a rare disease of unknown etiology that primarily affects women in their fifth to seventh decades. It is characterized by chronic watery diarrhea, normal mucosa upon endoscopic evaluation, and subepithelial collagen deposition on microscopic examination (1–3). Since the first description of this condition by the Swedish pathologist C.G. Lindstrom in 1976 (1), more than 500 cases have been described. There is no known etiology of this condition and associations include nonsteroidal antiinflammatory drugs (NSAIDs), spondyloarthropathies, rheumatoid arthritis, and inflammatory bowel disease (4–7). Other proposed etiopathological mechanisms have included an immunopathological process and a luminal cytotoxin (8–10). Here we report a case of collagenous colitis developing after recurrent C. difficile infection of the colon.

CASE REPORT: Acute Pancreatitis After Single-Dose Exposure to Propofol: A Case Report and Review of Literature

Little is known about the pathogenesis of most druginduced pancreatitis (1), but more than 85 drugs have been reported to cause acute pancreatitis (1, 2). The incidence of drug-induced pancreatitis has been reported to be 1.4% among 1613 patients treated for acute pancreatitis from all causes (3). Propofol, a lipid-based, sedative hypnotic agent widely used for the induction and maintenance of anesthesia, has been implicated as a cause of acute pancreatitis by altering lipid metabolism (4–9). However, most reported patients were chronically ill with multiple coexisting medical illnesses and medication use that may have contributed to development of acute pancreatitis while receiving propofol. We report a young nonalcoholic healthy woman without hyperlipidemia who developed acute pancreatitis after exposure to a single dose of propofol for nonabdominal surgery.

Glutathione Synthesis in the Exocrine Pancreas

Glutathione is essential for cellular cytoprotection, and in the exocrine pancreas, it is required for digestive enzyme synthesis. The purpose of these studies was to measure the capacity of the exocrine pancreas to synthesize glutathione, determine whether the pancreatic transsulfuration pathway has a role in providing cysteine needed for glutathione synthesis, and determine whether the glutathione synthetic capacity of the pancreas responds to pathologically relevant stresses. The activity of γ-glutamylcysteine synthetase, the key regulatory enzyme for glutathione synthesis, was 3.56 ± 0.29 mU/mg protein in the pancreas of fed rats, compared to 31 ± 4 in the liver and 116 ± 5 in the kidney. Studies using dispersed rat pancreatic acinar cells showed that the exocrine pancreas synthesizes glutathione from precursor amino acids and that the transsulfuration pathway is functionally intact in the pancreas and may serve as an important source of pancreatic cysteine. In mice, pancreatic γ-glutamylcysteine synthetase activity was induced 37% by corn oil, 77% by ethanol, and 88% by both treatments. Thus, the glutathione synthetic capacity of the pancreas is quantitatively less than that of the kidney or liver, but its key regulatory enzyme responds dynamically to pathologically relevant metabolic stresses, suggesting that glutathione is a key pancreatic cytoprotectant.

Nafcillin-associated hepatotoxicity : report of a case and review of the literature

SummaryNafcillin is a semisynthetic penicillin that is generally well tolerated with few side effects. Hepatic complications are rare but have a potential for serious liver dysfunction. This unusual complication causes a predominantly cholestatic injury, which can persist for prolonged periods even after discontinuing the medication. The pathophysiology may include direct cytotoxicity or an immune-mediate hypersensitivity. Treatment is generally supportive, except for severely symptomatic patients who may require steroids. We report a case of nafcillin-associated hepatotoxicity and review the literature of this disorder.

Case Report: Sclerosing Cholangitis, Inflammatory Bowel Disease, and Glomerulonephritis (A Case Report of a Rare Triad)

The association of primary sclerosing cholang itis (PSC) with in ̄ ammatory bowel disease (IBD) is well established. However, until recently, glomerulonephritis (GN) has not been recognized as a concomitant illness with these diseases. Including the ® rst description of this traid, there have been a total of four patients described (1± 4). There is a heterogeneity to their presentation particularly in regard to the GN. However, this association certainly suggests an immune-complex-mediated pathogenesis as a unifying theme. We describe a ® fth patient with this traid and the ® rst patient to have Crohn’ s disease with this presentation.

Effect of Octreotide on Stimulated Insulin Release from Pancreatic Tissue Slices

This study was designed to investigate a possible mechanism of action by which octreotide acetate causes insulin suppression in the denervated pancreas. Canine tissue slices were placed in a pH-adjusted medium with varying concentrations of glucose and octreotide acetate: Experiment 1, 30 min in basal medium with 0.6 mg/ml glucose; Experiment 2, addition of 6.0 mg/ml glucose; Experiment 3, addition of 4 μg octreotide acetate/70 ml (comparable to 100 μg/25 kg body weight); Experiment 4, addition of 16 μg octreotide acetate/70 ml; Experiment 5, incubation with 6.0 mg glucose/ml and 4 μg octreotide acetate/70 ml; Experiment 6, incubation with 6.0 mg glucose/ml and 16 μg octreotide acetate/70 ml; Experiment 7, preincubation with 4 μg octreotide acetate/70 ml, then with 6.0 mg glucose/ml; and Experiment 8, preincubation with 16 μg octreotide acetate/70 ml, then with 6.0 mg glucose/ml. Medium levels of insulin, glucagon, and amylase were collected at intervals during the incubation periods. There was an appropriate increase in the rate of insulin release to glucose stimulation in the high-glucose (6.0 mg/ml) group. There was no significant inhibition of basal or glucose-stimulated insulin release with either simultaneous or pretreatment of the canine pancreatic tissue slices with either concentration of octreotide acetate. These studies support an indirect mechanism by which octreotide acetate exerts its inhibitory effect on endocrine and exocrine function in the canine pancreas transplant model.