Fibrosing colonopathy in children with cystic fibrosis.

PURPOSE: Fibrosing colonopathy is a newly described entity seen in children with cystic fibrosis. The radiological hallmarks are foreshortening of the right colon with varying degrees of stricture formation. High-dose enzyme therapy has been implicated as the cause of this process. The purpose of this study is to review the author's experience with evaluation and treatment of these patients. METHODS: There are currently 380 patients being treated at our CF center. Fifty-five of these patients have been treated with high-dose enzyme therapy (> 5,000 units of lipase/kg). The medical records of these patients, who are at risk for developing fibrosing colonopathy, were reviewed for the presence of recurrent abdominal complaints, and the work-up and treatment of these symptoms. RESULTS: Chronic complaints of abdominal pain, distension, change in bowel habits, or failure to thrive were present in 24 of the 55 patients treated with high-dose enzymes. So far, 18 of these 24 patients have been evaluated by contrast enema. Thirteen of eighteen have been found to have fibrosing colonopathy characterized by foreshortening and strictures of the colon. Additional findings included focal strictures of the right colon (7 of 13), long segment strictures (5 of 13), and total colonic involvement (1 of 13). Nine patients with the most severe symptoms have undergone colon resection, including five segmental right colectomies, three extended colectomies (ileo-sigmoid anastomosis), and one subtotal colectomy with end-ileostomy. Pathological evaluation has shown submucosal fibrosis, destruction of the muscularis mucosa, and eosinophilia. No postoperative complications or deaths occurred. All nine postoperative patients have noted marked symptomatic improvement. Contrast enema follow-up results are available for six patients, and have documented no recurrent strictures to date. Three of four nonoperative patients have less severe symptoms and are currently being treated conservatively. The other family has refused surgery and the patient is being treated symptomatically. CONCLUSION: High-dose lipase replacement has been implicated as the etiology for FC and was present in all of our patients. Our cystic fibrosis center now routinely limits lipase to 2,500 U/kg per dose. We recommend the use of the contrast enemas to evaluate at-risk patients who have chronic abdominal complaints or who present with recurrent bowel obstruction. Colon resection should be performed in those with clinically and radiographically significant strictures with the expectation of a good outcome.

Correlation of intestinal lactulose permeability with exocrine pancreatic dysfunction.

Increased intestinal permeability to lactulose has been reported in patients with cystic fibrosis (CF). To determine whether this finding is unique to CF or whether it is related to accompanying exocrine pancreatic dysfunction, we evaluated 31 patients with CF and 10 with Shwachman syndrome who had variable degrees of pancreatic dysfunction, together with 17 healthy control subjects. There was no significant difference in the mean urinary lactulose excretion, expressed as the percentage of dose recovered, between CF and non-CF patients with pancreatic insufficiency (2.1% +/- 1.2% and 1.9% +/- 0.8, respectively) or between CF and non-CF patients with pancreatic sufficiency (0.6% +/- 0.5% and 0.6% +/- 0.3%, respectively). However, there was a significant difference in mean lactulose excretion between the pancreatic-insufficient and the pancreatic-sufficient patients (both CF and non-CF groups; p less than 0.001 and p less than 0.013, respectively). We further analyzed the results from 26 of the 41 patients (16 patients with CF and 10 non-CF patients) with pancreatic dysfunction who had previously undergone quantitative pancreatic function testing. A nonlinear, inverse relationship was found between urinary lactulose excretion and exocrine pancreatic function determined by duodenal trypsin output. These data confirm a direct relationship between intestinal lactulose permeability and the degree of exocrine pancreatic dysfunction, unrelated to the cause of the pancreatic disease.

Methane excretion and experimental colonic carcinogenesis.

To examine the association between methane (CH4) excretion and experimental colonic carcinogenesis, we measured CH4 excretion in rats treated with the colonic carcinogen azoxymethane (AOM, 7 mg/kg weekly for 10 weeks) and paired controls. CH4 excretion was not initially detected in either experimental or control groups, but all animals acquired positive CH4 excretion status by time of sacrifice (week 26). There was no difference between groups or among AOM-treated animals with and without tumors in the median time to onset of detectable CH4 excretion or in the amount of CH4 excreted. Our results fail to provide support for a link between CH4 excretion and experimental colonic dysplasia or adenocarcinoma.

Nonabsorbed carbohydrate: effect on fecal pH in methane-excreting and nonexcreting individuals.

To determine whether the acidifying effect of malabsorbed carbohydrate on fecal pH differed between methane-excreting and nonexcreting individuals, we administered the poorly absorbed disaccharide lactulose to five CH4 excretors and six CH4 nonexcretors. Lactulose, 20 g twice daily for 1 wk, significantly lowered fecal pH among CH4 nonexcretors as compared with CH4-excreting individuals (5.38 +/- 0.66 vs 6.90 +/- 0.61, p less than 0.01). To determine whether this observation was due to differences in acid production from bacterial carbohydrate fermentation, feces from each subject were incubated with lactulose. There were no differences in in vitro acid or hydrogen production between groups. We conclude that malabsorbed carbohydrate fails to induce in vivo colonic acidification in CH4 excretors. In contrast, in vitro fecal carbohydrate fermentation is similar among CH4 excretors and nonexcretors. These results suggest differences between these two groups in the colonic absorption of fermentation products.

Esophageal motor abnormalities in children and adolescents with scleroderma and mixed connective tissue disease.

To determine the frequency and nature of esophageal motor abnormalities in children and adolescents with scleroderma syndromes and mixed connective tissue disease, esophageal manometry was performed on seven patients with progressive systemic sclerosis, four patients with mixed connective tissue disease, and two patients with linear scleroderma. A total of 73% of patients with progressive systemic sclerosis and mixed connective tissue disease had symptoms of esophageal dysfunction. A significant association between the presence of Raynaud phenomenon and esophageal symptoms was noted. Esophageal motor abnormalities were detected in 73% of patients with progressive systemic sclerosis and mixed connective tissue disease; these abnormalities were characterized by decreased lower esophageal sphincter pressure and abnormal peristalsis in the distal two thirds of the esophageal body. They resemble those described among adults with progressive systemic sclerosis and mixed connective tissue disease but were not related to disease duration or to the presence of Raynaud phenomenon. Patients with linear scleroderma did not have esophageal symptoms and demonstrated only nonspecific motor abnormalities that did not worsen during several years of follow-up.

Thin-layer chromatographic determination of urinary excretion of lactulose, simplified and applied to cystic fibrosis patients.

Urinary excretion of orally administered lactulose is used as an index of intestinal permeability. We have developed a simple thin-layer chromatographic technique for measuring lactulose in urine, using silica gel 60 plates and a propanol-borate solvent system. Lactulose concentrations as low as 62.5 mg/L can be detected with high reproducibility and without interference by urinary chromogens. After oral administration, the urinary excretion of lactulose in 8 h equaled 2.33 (SD 1.86)% in 15 patients with cystic fibrosis, as compared with 0.13 (SD 0.12)% in 16 healthy subjects (P less than 0.001).

Physician efficiency and reimbursement: a case study.

Joint ventures between hospitals and doctors are being widely developed and reported as the most promising mechanism for building alliances, providing financial rewards, and accessing new markets. However, joint ventures cannot be structured to involve an entire medical staff directly. Likewise, they cannot motivate a medical staff to change medical practice patterns in order to improve a hospital's reimbursement efficiency. This article describes a system of physician economic efficiency criteria that is being used by one hospital in making medical staff reappointment decisions and has the effect of placing all physicians at risk individually for the hospital's reimbursement performance. Although somewhat controversial, this economic efficiency program has proven a remarkably effective tool for change.

Does measles really predispose to tuberculosis?

In recent years, textbooks and reviews on mechanisms involved in cellular immunity have emphasized that measles adversely influences tuberculous lesions. The medical literature was critically investigated for the basis of this claim. All field studies reviewed possessed strong deficiencies in the pertinent data and the methods of their collection. These deficiencies rendered invalid conclusions concerning the ability of measles to activate tuberculosis. Indirectly, there are also no adequate epidemiologic data to support the concept that measles suppresses tuberculous immunity when it suppresses tuberculin skin reactivity. Considering all the available information, one may conclude that if measles does have a deleterious influence on tuberculosis, it is probably at low frequency in most populations.