The role of Concanavalin A-binding fraction in cholesterol crystallization in native human bile

Background/Aims: Many Concanavalin A-binding glycoproteins have been proposed to influence cholesterol crystallization in human bile. This has been studied mainly by addition of the Concanavalin A-binding fraction to model bile. The physiological relevance of the proteins in native bile is not yet known. The aim of this study was to establish the role of the Concanavalin A-binding fraction in cholesterol crystallization in native human gallbladder bile.Methods: To determine the effects of the removal of Concanavalin A-binding fraction, fresh human gallbladder bile was incubated with either Concanavalin A-Sepharose or Sepharose alone. Beads were sedimented and crystallization was studied in the supernatant.Results: Extraction of Concanavalin A-binding fraction decreased crystallization in fast-nucleating biles (Crystal Detection Time <-4 days). Slow-nucleating biles were not affected. The effect could not be related to the content of known pronucleating proteins (IgA, IgM, haptoglobin, aminopeptidase N and α1-acid-glycoprotein), since the slow-nucleating biles contained similar amounts of these proteins.Conclusions: Although Concanavalin A-binding fraction always accelerated crystallization when added to model bile, removal of the same fraction from native bile often had no effect. We conclude that slow-nucleating biles in particular contain undertermined factors which regulate the activity of pronucleators.     

Platelet activating factor in stool from patients with ulcerative colitis and Crohn's disease.

BACKGROUND/AIMS: Platelet activating factor (PAF) is a potent endogenous mediator in inflammatory processes. The role of this mediator, especially in connection with the unknown etiology of chronic inflammatory bowel diseases, remains poorly understood. A determination of PAF in stool may be helpful in recognizing quiescent inflammations in chronic inflammatory bowel diseases. A simple and reliable method for the determination of PAF in stool seems to be necessary to achieve this goal. METHODOLOGY: PAF analysis was performed with the help of a commercial PAF radioimmunoassay (RIA) kit after solid phase extraction (SPE) of ethanolic stool extracts. PAF was determined in stool from 10 healthy volunteers (m = 4; f = 6), 13 patients with ulcerative colitis (m = 7; f = 6) and 15 patients with Crohn's disease (m = 9; f = 6). Fecal PAF concentrations were compared with activity index of disease, endoscopic index, localization of lesions, leukocyte count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), medical prednisolone treatment, sex and age of the patients. RESULTS: In healthy volunteers, no PAF was detectable in stool. In patients with Crohn's disease 319.2 +/- 143.5 pg PAF/g stool and in patients with ulcerative colitis 824.9 +/- 408.7 pg PAF/g stool could be determined. A significant correlation (p < 0.05) was found between PAF-content in stool and the endoscopical index and intestinal localization of inflammatory lesions. No further correlations could be detected in our patients. CONCLUSIONS: Fecal PAF assessment may be used clinically as a non-invasive method to estimate severity of mucosal inflammation in patients with inflammatory bowel disease (IBD).     

'Conversion' from ulcerative colitis to Crohn's disease associated with corticosteroid treatment.

A man who was a non-smoker presented with clinical, histological, and radiological features typical of distal ulcerative colitis. Prolonged treatment with corticosteroids was associated with the development of numerous granulomata, stricturing, and perianal disease. It is speculated that the immunosuppression associated with the corticosteroid treatment may have induced a change from ulcerative colitis to Crohn's disease of the colon. This case report lends support to the hypothesis that these conditions may just represent different forms of a continuum of inflammatory bowel disease.     

Leucocyte scintigraphy to localize inflammatory activity in ulcerative colitis and Crohn's disease.

The validity of using autologous leucocytes labelled with technetium -99m hexamethyl-propyleneamine-oxine (Tc-HMPAO) for scintigraphy in inflammatory bowel disease was evaluated in 12 patients with clinically active ulcerative colitis (UC) and 10 with Crohn's disease (CD). Colonoscopy and biopsy were used as reference. Scintigrams taken 1 h and 3 h after leucocyte reinjection were evaluated blindly by two independent observer groups. Full agreement was found in 11 of 12 UC patients when compared with colonoscopy but in only 3 of 10 CD patients. Segments with agreement in CD patients often showed neutrophilic granulocyte infiltration at biopsy. The judgements of clinicians and physiologists differed for only 2 of totally 70 UC segments but for 13 of 59 CD segments (kappa, 0.94 and 0.52). It is concluded that Tc-HMPAO scintigraphy might be an alternative to colonoscopy in the control of disease extent in UC. In CD patients the technique might warn about infections complications.     

Long-term ileostomy complications in patients with ulcerative colitis and Crohn's disease

Ileostomy complications in 203 patients operated on with proctocolectomy and ileostomy for ulcerative colitis and Crohn's disease were investigated prospectively. The patients were examined at regular intervals by interview and thorough examination of the stoma. Stomal dysfunction was carefully assessed and patients presenting with surgical complications were admitted for reconstruction. The crude rate of ileostomy complications necessitating reconstruction was 34% and significantly higher in patients with Crohn's disease compared with patients with ulcerative colitis. The cumulative rate of surgical revision after 8 years was 75% in the former group and 44% in the latter. Ileostomy stenosis and sliding recession were the two most common indications for reconstruction. Eighty-three per cent of the revisions were performed as local procedures, making a formal laparotomy unnecessary. Causative factors such as surgical technique, length of concomittant ileal resection and postoperative weight gain were analysed for possible influence on the rate of reconstruction, but no significant association was identified.     

Evaluation of inflammatory activity in Crohn's disease and ulcerative colitis

Crohn's disease and ulcerative colitis evolve with a relapsing and remitting course. Determination of inflammatory state is crucial for the assessment of disease activity and for tailoring therapy. However, no simple diagnostic test for monitoring intestinal inflammation is available. Noninvasive markers give only indirect assessments of disease activity. Histopathological or endoscopical examinations accurately assess inflammatory activity, but they are invasive, time consuming and expensive and therefore are unsuitable for routine use. Imaging procedures are not applicable for ulcerative colitis. The usefulness of ultrasound and Doppler imaging in assessing disease activity is still a matter of discussion for Crohn's disease, and an increased interest in computed tomography enterograph (CTE) has been seen, mainly because it can delineate the extent and severity of bowel wall inflammation, besides detecting extraluminal findings. Until now, the available data concerning the accuracy of magnetic resonance enterography in detecting disease activity is less than CTE. Due to this, clinical activity indices are still commonly used for both diseases.     

Serum lysozyme in Crohn's disease and ulcerative colitis.

Serum lysozyme (muramidase) was determined in 72 patients with Crohn's disease or ulcerative colitis. Serum lysozyme was elevated in both disease groups. The mean enzyme level was significantly higher in Crohn's disease than in ulcerative colitis, but there was a considerable overlapping between the groups, which makes serum lysozyme determination of dubious value in the differential diagnosis between Crohn's disease and ulcerative colitis. No correlation was found between the serum lysozyme concentration and the activity of the diseases.     

Pericarditis associated with ulcerative colitis and Crohn's disease

Extracolonic manifestations of inflammatory bowel disease are common and diverse. However, cardiac complications are unusual and we therefore wish to report two cases in which pericarditis occurred. The first was a patient with Crohn's disease of the colon, in whom the pericarditis developed postoperatively. In the second case an acute pericarditis came on simultaneously with the initial presentation of ulcerative colitis.     

Survival rate in Crohn's disease and ulcerative colitis.

The survival rate in 709 patients with chronic inflammatory bowel disease (CIBD) was calculated by the log rank test. There were 297 patients with Crohn's disease (CD) and 412 patients with ulcerative colitis (UC). In both diseases there was a survival rate of about 94% in the first year of observation against an expected rate of 99.5% in a general population matched for sex and age. This was because a large number of patients were severely ill at their first admission and required immediate or early surgery. During the subsequent 11 years the death rate in CIBD was higher (two to three times) than in the general population. After 12 years the survival rate was about 77% in both CD and UC. The difference was statistically insignificant. There was no significant difference in the sex ratio. The cancer rate was low. No gastrointestinal cancer occurred among patients with CD. Colorectal cancer was found in four patients with UC, three of whom presented with cancer on their first admission. It is concluded that recurrence and reoperation for recurrence in Crohn's disease have not impaired the prognosis compared to ulcerative colitis in this series.     

Immunological studies in ulcerative colitis. VIII. Antibodies to colon antigen in patients with ulcerative colitis, Crohn's disease, and other diseases.

Sera from patients with ulcerative colitis or Crohn's disease had elevated titers to colon antigen from germ-free rats significantly more often than sera from patients with gastroenteritis, irritable colon, non-gastrointestinal diseases, and healthy controls. Elevated anticolon titers in significant frequency were also found in patients with liver cirrhosis, urinary tract infections, and in polyposis coli and their relatives. Females with ulcerative colitis had, on an average, higher titers than men especially in the age group 30 years and over. In Crohn's disease the antibody titers often increased with time--as opposed to those in ulcerative colitis and non-gastrointestinal diseases. In conjunction with results published earlier, the present work supports the assumption that the antibodies in ulcerative colitis patients react with antigenic determinants distinct from those recognized by the colon antibodies present in other groups, including patients with Crohn's disease and polyposis.     

Investigation of genetic markers in patients with Crohn's disease and ulcerative colitis

Inflammatory bowel diseases (IBD) as Crohn's disease (CD) and ulcerative colitis (UC) are believed to have a genetic basis. Additional factors are supposed to promote the development of IBD. However, apart from a few reports of HLA associations which await confirmation by other groups strong associations to (a) particular genetic marker(s) are still lacking. We here report on previously unobserved associations of CD to MNSS and UC to the immunoglobulin heavy chain allotype Gm 1,-2,10. We suggest that these factors play a role in a wider spectrum of genetic markers for the development of IBD.     

Ornithine decarboxylase in colonic mucosa from patients with moderate or severe Crohn's disease and ulcerative colitis.

Polyamines, as well as ornithine decarboxylase (ODC), the enzyme involved in their synthesis, were reported to be closely related to cell proliferation. In Crohn's disease and ulcerative colitis, cell destruction and proliferation increase in the active stage. The aim of the present study was to determine the ODC in both involved and uninvolved areas of the colonic mucosa of active Crohn's disease and ulcerative colitis patients. The patients were divided in two groups, owing to the different level of activity (severe or moderate), by means of clinical endoscopy, laboratory, and histology evaluations. Subjects with suspected disease, but endoscopically unconfirmed, were used as controls. In all ulcerative colitis and Crohn's disease patients the ODC values both in involved and uninvolved mucosa were significantly lower than in controls. In severe Crohn's disease ODC was significantly reduced versus moderate Crohn's disease only in affected tissues. In all ulcerative colitis patients (moderate or severe) the ODC was significantly decreased in involved mucosa compared with uninvolved mucosa. Severe ulcerative colitis showed the significantly lowest ODC. We suggest that the significant decrease of ODC in the bowel mucosa is closely related to the severity of the disease. The highest decrease of ODC in ulcerative colitis patients would be due both to the enhanced cell destruction, and to the feed-back from exogenous increased polyamine production (bowel bacteria, cell desquamation). Therefore ODC would be considered a sensitive index of the inflammatory derangement of the mucosa, especially in acute ulcerative colitis. We conclude that this behaviour may result in an enhanced risk of neoplasia.     

Increased activity in the biliary Con A-binding fraction accounts for the difference in crystallization behavior in bile from Chilean gallstone patients compared with Dutch gallstone patients

Chile has one of the highest prevalences of cholesterol gallstone disease in the world. Recent data indicate that this is partly caused by genetic (Indian) factors. However, the causal factors inducing increased gallstone formation have not been elucidated. The aim of this study was to compare biliary composition and cholesterol crystallization in bile from patients of high and moderate risk areas (Chile and The Netherlands) for gallstone disease. Bile was sampled at cholecystectomy from 30 Chilean and 26 Dutch gallstone patients. The Con A-binding fraction (CABF) was extracted from fresh native bile samples by incubation with Con A-sepharose. Reconstitution of the CABF to the Con A-extracted native bile induced almost full recovery of crystallization confirming the validity of this technique. There was no difference between the two groups regarding sex and age. Chilean bile nucleated significantly faster (3.5 +/- 0.6 vs. 7.9 +/- 1.5 days) despite the fact that Dutch bile had a significantly higher cholesterol saturation index (CSI) (1.6 vs. 1.2, P = .01). The total lipid content was not different. Chilean bile contained more total protein (5 vs. 2.9 mg/mL, P = .008). IgG, IgM, Haptoglobin and alpha-1-acid glycoprotein were not different between the two groups. IgA, though, was significantly higher in the Chilean samples (0.44 vs. 0.19 mg/mL, P < .001). Extraction of CABF increased crystal observation time (COT) and decreased crystal growth in both groups. However, the effects were much more pronounced in the Chilean samples. Compared with Dutch bile, Chilean bile crystallizes much faster despite a lower CSI. Chilean bile contains an increased content of Con A-binding nucleation promoting activity.     

Muscle cell electrolytes in ulcerative colitis and Crohn's disease.

The intracellular electrolyte concentrations in skeletal muscle from 15 patients with ulcerative colitis or Crohn's disease were examined. In patients with diarrhea not receiving potassium, muscle cell potassium and magnesium were low and sodium insignificantly elevated. By contrast, largely normal muscle cell electrolyte concentrations were found in patients receiving potassium or having a normal intestinal function. Supported by the existence of normal muscle cell electrolytes in a control group of patients receiving prednisone for extraintestinal diseases it was stated that glucocorticoid treatment does not affect the muscle cell electrolytes unless such treatment is effective in controlling the intestinal function. Potassium - and possibly magnesium - supplementations are recommended in cases with diarrhea.     

Glucosamine synthetase activity of the colonic mucosa in ulcerative colitis and Crohn's disease.

Glucosamine synthetase is the first enzyme in glycoprotein biosynthesis, catalysing the formation of glucosamine-6-phosphate, from which N-acetylglucosamine is formed. The levels of this enzyme in normal human colonic mucosa (in colectomy specimens and rectal biopsies) were found to be 13-8 +/- 4-0 micron mol glucosamine synthesised/h/g wet wt. In the colonic mucosa in ulcerative colitis and Crohn's colitis the enzyme level was diminished when there was loss of epithelial cells in the mucosa, although not when there was just loss of goblet cells. In patients recovering from an acute attack of ulcerative colitis, the enzyme levels rose to a peak above the normal range, an effect which did not occur in patients who did not recover promptly. This recovery peak may be related to the synthesis of gastrointestinal mucus, or immunoglobulin, or the secretory component of IgA, all of which contain large amounts of N-acetylglucosamine.     

Serum lysozyme levels in Crohn's disease and ulcerative colitis.

Serum lysozyme levels were determined in healthy volunteers, patients with Crohn's disease, and patients with ulcerative colitis. The mean concentration in Crohn's disease was significantly greater than in the other groups. In patients with Crohn's disease, as well as in patients with ulcerative colitis, the lysozyme levels correlated with the severity of the disease process and with the extent of the lesions: the more severe the disease and the more extensive the involvement, the higher the lysozyme levels. However, the lysozyme values of the different groups overlapped considerably. Our results indicate that lysozyme determinations have only limited discriminative value for the diagnosis of Crohn's disease and for determining the severity and the extent of the disease process in the individual patient.     

Crohn's disease and ulcerative colitis in the same patient.

A well documented case of a patient with both Crohn's disease and ulcerative colitis is presented. A 29 year old woman underwent resection of her terminal ileum and ascending colon for typical Crohn's disease with ileocolitis. Eleven years later, an ileoproctocolectomy was performed for typical ulcerative colitis involving the left colon. The resection specimen also showed evidence of colonic Crohn's disease near the anastomotic site. This unusual case shows that Crohn's disease and ulcerative colitis can occur in the same patient. The rarity of such cases supports the concept that Crohn's disease and ulcerative colitis are separate entities, rather than different manifestations of the same disease process.