PMN-elastase in assessment of patients with inflammatory bowel disease

PMN-elastase is a proteinase released by activated neutrophils. PMN-elastase was determined in two independent populations with inflammatory bowel disease. In an unselected population of 70 consecutive patients with Crohn's disease and 24 patients with ulcerative colitis with different degrees of disease activity plasma PMN-elastase levels were statistically significantly higher in patients with active than in patients with inactive disease [Crohn's disease: 80.5±33.2 ng/ml vs 60.1±24.6 ng/ml (means±sd),P=0.0017; ulcerative colitis: 98.2±54.9 ng/ml vs 59.2±16.8 ng/ml,P=0.026]. PMN-elastase levels in feces were also higher in patients with active Crohn's disease (23.6±15.3 ng/g vs 13.6±12.5 ng/g,P=0.0021) and active ulcerative colitis (46.5±60.5 ng/g vs 20.2±25.0 ng/g,P=0.46), but the difference reached significance only in Crohn's disease. Correlation of disease activity and PMN-elastase in individual patients showed a statistically significant correlation between plasma and fecal elastase concentrations and disease activity in ulcerative colitis (plasma:r=0.72,P<0.001; feces:r=0.423,P<0.001) but not fecal elastase concentrations (r=0.0083,P=0.485) correlated significantly with disease activity. Plasma PMN-elastase correlated weakly with fecal PMN-elastase levels in Crohn's disease (r=0.431,P<0.01) and in ulcerative colitis (r=0.515,P=0.05). In 28 patients with highly active Crohn's disease [median severity activity index (SAI) 203] and 11 patients with highly active ulcerative colitis [median Rachmilewitz index (RI) 14] studied before and four weeks after steroid therapy, treatment lowered the median SAI to 140 and the median RI to 4.5. Mean plasma elastase concentrations decreased concomitantly from 83±44.9 ng/ml to 61.8±25.8 (P=0.0035) in patients with Crohn's disease and from 110±49.5 to 71.6±28.8 ng/ml (P=0.0069) in patients with ulcerative colitis. In conclusion, there is a release of PMN-elastase in active IBD, which can be detected in plasma as well as in feces. Plasma elastase levels reflect disease activity in patients with IBD. The variation of the data and the large overlap between different groups, however, strongly reduce the clinical value.This research was supported by the SFB 154 of the Deutsche Forschungsgemeinschaft. V. Gross is supported by a Heisenberg-Stipendium of the Deutsche Forschungsgemeinschaft.     

Chemotactic activity in inflammatory bowel disease

An important histologic feature of inflammatory bowel disease (IBD) is infiltration of the colonic mucosa with neutrophils. To investigate the nature of the chemotactic agents responsible for this infiltration, colonic mucosa from three normals and nine patients with inflammatory bowel disease (seven ulcerative colitis, two Crohn's colitis) was assayed for chemotactic activity for human neutrophilsin vitro in a Boyden chamber. There was more (>10-fold more) chemotactic activity in homogenates of inflammatory bowel disease mucosa than in homogenates of normal colonic mucosa. Analysis of the chemotactic activity in the inflammatory bowel disease mucosa revealed that most was lipid extractable. Moreover, when the lipid extract was fractionated by reverse-phase high-pressure liquid chromatography, the only fraction with significant chemotactic activity was the fraction that coeluted with leukotriene B₄. The chemotactic response to IBD mucosa was blocked by anti-LTB₄ antisera. The amount of chemotactic activity in lipid extracts of different inflammatory bowel disease specimens correlated well with the concentration of leukotriene B₄ measured by UV absorbance (250 ng/g of mucosa). These data suggest that leukotriene B₄ is an important stimulus to neutrophil chemotaxis in inflammatory bowel disease and, thus, may play a major role in the amplification of the inflammatory response in this condition.This work is supported by a grant from the National Foundation for Ileitis and Colitis and grant AM-33165 from the National Institutes of Health.     

Mucosal glucosamine synthetase activity in inflammatory bowel disease

Abnormalities in colonic glycoprotein synthesis have been implicated in the pathogenesis of ulcerative colitis and Crohn's disease. Glucosamine synthetase is the rate-limiting step in the biosynthesis of gastrointestinal glycoprotein and has been measured in control subjects (N=23) and patients with ulcerative colitis (N=26) or Crohn's disease of the colon (N=20) classified according to the macroscopic status of the rectum. Glucosamine synthetase activity was relatively constant around the normal colon but lower levels were found in the terminal ileum. In ulcerative colitis, glucosamine synthetase activity was similar to controls (24.0±1.9) mmol/g wet (wt/hr) irrespective of disease activity (quiescent:N=13, =27.3±1.9; activeN=16, =26.2±2.3). Rectal glucosamine synthetase activity was normal in the presence of active Crohn's proctocolitis (29.4±3.1) but raised in patients with Crohn's colitis and rectal sparing (37.2±4.9P<0.02). Glucosamine synthetase activity was strongly influence by the degree of epithelial preservation.     

Hospital discharges for inflammatory bowel disease

The present study analyzes time trends of inflammatory bowel disease (IBD) in England-Wales and the United States based on nationwide hospitalization statistics. Because these statistics cover the total population of each country, they may give a more representative picture of the true trends than previous analyses concerning only one region or health center. The Hospital In-patient Enquiry was used to evaluate time trends in England-Wales from 1962 to 1985, data from the National Hospital Discharge Survey and the Commission on Professional Activities were used for trends in the United States from 1970 to 1987. A rise of Crohn's disease persisted unabated in the old age groups throughout the observation period. It was less marked in those aged under 35 and reached a plateau during the most recent decade. In ulcerative colitis, discharge rates increased in the older age groups, but remained constant or declined in the middle or younger age groups, respectively. Similar trends were observed in all three surveys. The hospitalization data confirm similar age-specific trends of mortality. The difference between younger and older age groups suggests that generations born 60–80 years ago have become more likely to be affected by IBD leading to hospitalization and mortality. As these high-risk generations grow older, there is a relative rise of hospitalization and mortality from IBD in these subjects.Supported by grant So 172/1-1 from the Deutsche Forschungsgemeinschaft.     

Metabolic features of inflammatory bowel disease in a remission phase of the disease activity

Capristo E, Mingrone G, Addolorato G, Greco AV, Gasbarrini G (Sacred Heart Catholic University, Rome, Italy). Metabolic features of inflammatory bowel disease in a remission phase of the disease activity. J Intern Med 1998; 243 : 339–47.

Objectives

To evaluate the anthropometric and metabolic characteristics of patients with Crohn's disease (CD) and ulcerative colitis (UC), comparing both groups with healthy volunteers.

Design

A cross-sectional study.

Setting

The Department of Internal Medicine, Catholic University Hospital, Rome, Italy.

Subjects

Thirty-four patients with biopsy-proven inflammatory bowel disease (18 CD; 16 UC) in clinical remission (SCDAI <3 and Powell–Tuck index <4) not receiving steroid therapy.

Interventions

All patients had a clinical examination.

Main outcome measures

Blood indicators of inflammation and nutritional status. Body composition was assessed by both anthropometry and bioimpedance and metabolic variables were measured by indirect calorimetry over a 60–90 min period.

Results

CD had a lower body weight than both controls (58.1 kg, range 41.5–71.0 vs. 66.4 kg, range 57.0–76.0; P < 0.001) and UC) 58.1 kg, range 41.5–71.0 vs. 69.6 kg, range 50.5–94.0; P < 0.001). Fat-free mass (FFM) did not differ between the groups, whilst fat mass was significantly lower in CD than in UC (P < 0.05) and controls (P < 0.001). Normalizing the basal metabolic rate by FFM, a higher value was found in CD compared with UC (143 kJ kg^?1 d–^?1, range 97.5–179 vs. 133 kJ kg^?1 d^?1, range 123–148; P < 0.05) and control subject 143 kJ kg^?1 d^?1, range 97.5–179 vs. 134 kJ kg^?1 d^?1, range 122–162; P < 0.05). The nonprotein respiratory quotient was significantly lower in CD compared to UC 0.80, range 0.73–0.84 vs. 0.84, range 0.79–0.91; P < 0.01) and controls (0.80, range 0.73–0.84 vs. 0.83, range 0.81–0.87; P < 0.001), with a consequently higher lipid oxidation rate in CD.

Conclusions

CD subjects showed a decreased fat mass and enhanced utilization of lipids compared with UC and controls. These data could be explained by the larger intestinal involvement and considered as a contribution to lipid tissue wasting in CD.

     

Inflammatory bowel disease: dogmas and heresies

Perception of a disease state by the practising physician is based on how easily the diagnosis can be made and how predictable the outcome of the chosen therapy is. The academic investigator perceives the same disease based on how well its cause and mechanism are understood, and how rational pathophysiology-based treatments are. Because of incomplete knowledge, neither the practising physician nor the academic investigator are comfortable in dealing with inflammatory bowel disease, and both seek help in the dogmas and heresies inevitably associated with chronic disease of unknown aetiology.     

Careful patient selection may improve response rates to infliximab in inflammatory bowel disease

BACKGROUND AND AIM: The use of infliximab in the treatment of Crohn's disease (CD) is acceptable and appears to be effective in ulcerative colitis (UC). Careful patient selection, resulting in infliximab only for truly refractory inflammatory bowel disease (IBD), may improve its efficacy. The present study aimed to determine if careful patient selection improved infliximab efficacy in IBD. Methods: CD or UC/IBD unclassified patients (Montreal classification) were considered for infliximab treatment only after failure of disease control with conventional therapies and confirmation of active disease. Patients with purely luminal IBD received a single infliximab dose. Patients with fistulizing disease (with or without luminal disease) received infliximab at 0, 2 and 6 weeks. Changes to Harvey Bradshaw (HBI) for inflammatory CD and Colitis Activity Index (CAI) for UC/IBDU were used to determine the response and remission rates. In fistulizing CD, a remission was sustained cessation of drainage and resolution of the fistula. Response was correlated to inflammatory marker levels. RESULTS: Seventy IBD patients were treated. In CD, 85.2% (46/54) had active luminal and 40.7% (22/54) had fistulizing disease. In luminal CD, at 8 weeks a single infliximab dose induced remission in 75% (24/32) of patients compared to 92.9% (13/14) after infliximab at 0, 2 and 6 weeks. Fistulizing disease responded in 77.2% (17/22) and remitted in 50% (11/22) of patients at 8 weeks. In UC/IBDU, 75% (12/16) responded and 43.8% (7/16) of patients were in remission at 8 weeks. CONCLUSION: Careful patient selection may improve infliximab's efficacy and clinical remission appears greater after induction with three infliximab doses in CD. Clinical efficacy is suggested for UC/IBDU.     

Childhood infections and the risk of inflammatory bowel disease

Adults with inflammatory bowel disease from North Carolina were questioned during 1986 and 1987 to assess risk due to a variety of childhood infections and treatments with antibiotics. Responses were compared with those of neighbor controls. Persons with Crohn's disease were more likely to report an increased frequency of childhood infections in general (odds ratio 4.67, 95% CI 2.65–8.23) and pharyngitis specifically (odds ratio 2.14, 95% CI 1.30–3.51). This was validated by an increased frequency of tonsillectomy (odds ratio 1.53, 95% CI 1.07–2.20). Crohn's cases were more likely to report frequent treatment with antibiotics for both otitis (odds ratio 2.07, 95% CI 1.03–4.14) and pharyngitis (odds ratio 2.14, 95% CI 1.20–3.84). Although Crohn's cases were more likely to report frequent exposure to penicillin (odds ratio 1.81, 95% CI 0.98–3.31), there did not appear to be excess risk conferred by penicillin after controlling for frequency of infections. Persons with ulcerative colitis also reported an excess of infections generally (odds ratio 2.37, 95% CI 1.19–4.71), but not an excess of specific infections or treatments with antibiotics. Persons who reported an increased frequency of infections tended to have an earlier onset of Crohn's disease (P<0.0001) and ulcerative colitis (P=0.04). Finally, it was noted that urban living in childhood increased the risk for Crohn's disease. We conclude that childhood infections may be a risk factor for Crohn's disease and may presage the early onset of disease.This research was supported in part by grants from the Crohn's and Colitis Foundation of America and the National Irstitutes of Health (P30 DK34987, T32 DK07364 and RR00046).     

Frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece and review of the literature

BACKGROUND: Inflammatory bowel disease mainly affects the bowel but also has extraintestinal manifestations. AIMS: To report the frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece. PATIENTS; The data files of 256 inflammatory bowel disease patients (diagnosis between 1983-19971 were analysed. METHODS: Retrospective investigation of patient files. RESULTS: In patients with ulcerative colitis: 13.9% (30/215) had developed skin manifestations, 6% (13/215) had kidney stones, 1.39% (3/215) had iridocyclitis, 1.86% (4/215) had primary sclerosing cholangitis, 4.18% (9/215) had sacroiliitis, 8.31% (18/215) had peripheral arthalgias, 2.3% (5/215) had colitic arthritis and finally 1.39% (3/215) had deep vein thrombosis). In patients with Crohn's disease: 24.3% (9/37) had developed skin manifestations, 5.4% (2/37) had kidney stones, 2.7% (1/37) had iridocyclitis, 16.2% (6/37) had sacroiliitis, 8.1% (3/37) had peripheral arthralgias, 5.4% (2/37) had colitic arthritis and, finally, 8.1% (3/37) had deep vein thrombosis. Sacroiliitis (p = 0.01), deep vein thrombosis (p = 0.04) and erythmema nodosum (p = 0.01) were more common in patients with Crohn's disease. CONCLUSIONS: Extraintestinal manifestations are not rare in patients with inflammatory bowel disease, especially in Crohn's disease patients, in our area, but have, generally, a mild profile.     

Antibacterial and antimycobacterial treatment for inflammatory bowel disease

A variety of medicines have been used for the treatment of inflammatory bowel disease. Antibacterial therapy has demonstrated promise by both improving symptoms and causing disease remission. The mechanism is unknown, but may be related to either eliminating a key pathogen, decreasing the number of bacterial secretory products or defective particles, a direct immunomodulating effect, or reducing secondary bacterial invasion. Historically, a large number of bacterial species have been suspected as being major contributors to the etiology of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. Many trials of antibacterial agents have been carried out in inflammatory bowel disease. Recently, treatments have focused on Gram-negative anaerobes and mycobacteria. The present paper briefly reviews antimicrobial and antimycobacterial treatments in inflammatory bowel disease.     

Detection of Listeria monocytogenes by polymerase chain reaction in intestinal mucosal biopsies from patients with inflammatory bowel disease and controls

BACKGROUND AND AIMS: Components of the intestinal microflora are believed to play an important role in the pathogenesis of inflammatory bowel disease (IBD) in genetically susceptible hosts acting either as a non-specific antigenic stimulus or as a specific pathogen. Listeria monocytogenes has been suggested as an organism with the potential to cause IBD. The objective of the present study was to investigate the prevalence of L. monocytogenes DNA in intestinal biopsies from patients with IBD and from non-IBD controls by using nested polymerase chain reaction (PCR). METHODS: The DNA was extracted from 274 colonoscopic biopsies, which were obtained from 23 patients with Crohn's disease (CD), 28 with ulcerative colitis (UC) and 39 non-IBD control patients. Nested PCR amplification was used to detect the presence of the L. monocytogenes listeriolysin O (hly) gene. The sequences of positive PCR products were determined and compared with databases. RESULTS: The sensitivity of our nested PCR was 10 fg L. monocytogenes DNA. Overall, L. monocytogenes DNA was detected in 13.0% patients with CD, 17.9% patients with UC and 25.6% non-IBD control patients or in 29 of 274 (10.6%) endoscopic biopsies. Among them, L. monocytogenes DNA was detected in four of 67 (6%) biopsies from patients with CD, five of 94 (5.3%) biopsies from patients with UC and 20 of 113 biopsies (17.7%) from non-IBD control patients. Sequence analysis of positive PCR products demonstrated more than 95% similarity to the hly gene sequence of L. monocytogenes, confirming the authenticity of our PCR products. CONCLUSION: Listeria monocytogenes DNA was detected in the intestine of both patients with IBD and in non-IBD control patients, probably reflecting the widespread presence of this organism in the environment. The low yield of positive biopsies in our IBD patients (5-6%) and the fact that the detection rate of L. monocytogenes DNA was similar in endoscopic biopsies from IBD patients and non-IBD controls does not support a direct role for L. monocytogenes in the pathogenesis of IBD, at least in New Zealand patients.     

Assessment of disease activity and localization in inflammatory bowel disease using 99mTc-labelled leucocytes

Abstract Disease activity and regional extent of disease was studied in 20 patients with inflammatory bowel disease (13 with Crohn's disease and seven with ulcerative colitis). Autologous white cells from patients and controls were labelled with ^99mTc-stannous colloid, reinjected, and the faecal excretion of the labelled leucocytes was assessed over 48 h. In patients with Crohn's disease, the faecal excretion correlated with severity of disease as judged by the Harvey-Bradshaw index. In 18 of the 20 patients the extent of the inflammatory bowel disease as indicated by the scan image corresponded with the radiological and colonoscopic findings. The ^99mTc-stannous colloid label has advantages over indium-111 and the faecal excretion of labelled leucocytes has potential as a simple, objective measure of disease activity.     

Decreased trabecular bone mineral density in newly diagnosed inflammatory bowel disease patients in Korea

BACKGROUND: Decreased bone mineral density (BMD) is common in Western patients with inflammatory bowel disease (IBD). However, BMD has never been studied in Asia where the demographic and socio-economic status are different from the West. The aim of this study was to investigate the prevalence and mechanisms of osteopenia in newly diagnosed Korean patients with IBD. METHODS: We studied 14 patients with Crohn's disease (CD) and 25 patients with ulcerative colitis (UC), all of whom had never been treated with corticosteroids. Bone mineral density was measured in the lumbar spine and the femoral neck by dual energy X-ray absorptiometry. Biochemical parameters including serum osteocalcin, parathyroid hormone, plasma inactive and active vitamin D, and urinary deoxypyridinoline were measured. RESULTS: The BMD Z score at the lumbar spine was lower both in CD and in UC patients, but there was no significant difference between the two groups. There was no significant difference in nutritional status or biochemical parameters of bone metabolism between patients with a normal BMD and those with a decreased BMD. CONCLUSIONS: Low BMD at the lumbar spine is common in newly diagnosed Korean patients with IBD, a result which is similar to Western studies. The mechanism for low bone mass remains undetermined; however, nutritional status and hormonal parameters of bone metabolism, and ethnic differences are not likely to be an important factor in the pathogenesis of this bone loss.     

Detection of Chlamydia pneumoniae by polymerase chain reaction-enzyme immunoassay in intestinal mucosal biopsies from patients with inflammatory bowel disease and controls

BACKGROUND AND AIM: It has been suggested that Chlamydia is an organism that may have the potential to cause inflammatory bowel disease (IBD) in susceptible individuals. Chlamydia pneumoniae has emerged as an important human pathogen in the last decade. The objective of the present study was to investigate the frequency of the presence of C. pneumoniae DNA in intestinal biopsies from patients with IBD and from non-IBD controls. METHODS: The DNA was extracted from 222 colonoscopic biopsies, which were obtained from 11 patients with Crohn's disease (CD), 18 patients with ulcerative colitis (UC) and from 37 non-IBD control patients. The presence of the C. pneumoniae omp1 gene and C. trachomatis 16S rRNA gene was determined using a rapid and sensitive polymerase chain reaction-enzyme immunoassay (PCR-EIA). RESULTS: The C. pneumoniae-specific DNA was detected in 32 (14.4%) of 222 endoscopic biopsies. Among them, C. pneumoniae DNA were found in nine of 42 (21.4%) biopsies from patients with CD, nine of 59 (15.3%) biopsies from patients with UC, and 14 out of 122 (11.4%) biopsies from non-IBD control patients, respectively. Moreover, the percentage of patients with at least one biopsy positive for C. pneumoniae was higher, although not statistically significant, in CD (36.4%) and UC patients (38.9%) compared to non-IBD controls (16.2%). In contrast, C. trachomatis DNA was detected in only two of 222 (0.9%) biopsy samples. CONCLUSION: The C. pneumoniae DNA was detected in the intestine of both patients with IBD and in non-IBD control patients, probably reflecting the high prevalence of this organism in the environment. The moderate yield of positive biopsies in our IBD patients and the fact that the detection rate of C. pneumoniae DNA was similar in endoscopic biopsies from IBD patients and non-IBD controls does not support a direct role for this organism in the pathogenesis of IBD.     

Role of polymorphisms in the interleukin-10 gene in determining disease susceptibility and phenotype in inflamatory bowel disease

Interleukin-10 (IL-10) has a key role in regulating mucosal inflammation. The role of functional polymorphisms at positions –627 and –1117 in the IL-10 gene as candidate susceptibility loci in inflammatory bowel disease and their importance in determining disease extent were evaluated in 159 patients with ulcerative colitis (83 left-sided; 76 extensive), 90 patients with Crohn's disease (22 small bowel; 29 large bowel; 39 both), and 227 controls. Genotyping was performed either by PCR-RFLP assays (–627 site) or SSCP analysis (–1117 site). An excess of –627A allele was observed in patients with left-sided colitis (52%) compared with controls (33%; P = 0.004) suggesting that IL-10 may influence the extent of the disease. These results were not replicated in a newly recruited group (N = 100) of patients with UC. We conclude that polymorphisms at –627 and –1117 sites in the IL-10 gene do not contribute to the susceptibility to IBD or determining the extent of the disease in our population.     

Extraintestinal manifestations in inflammatory bowel disease

Inflammatory bowel diseases (IBD) can be really considered to be systemic diseases since they are often associated with extraintestinal manifestations, complications, and other autoimmune disorders. Indeed, physicians who care for patients with ulcerative colitis and Crohn's disease, the two major forms of IBD, face a new clinical challenge every day, worsened by the very frequent rate of extraintestinal complications. The goal of this review is to provide an overview and an update on the extraintestinal complications occurring in IBD. Indeed, this paper highlights how virtually almost every organ system can be involved, principally eyes, skin, joints, kidneys, liver and biliary tracts, and vasculature (or vascular system) are the most common sites of systemic IBD and their involvement is dependent on different mechanisms.     

Management of inflammatory bowel disease in adults

Optimal care of the inflammatory bowel diseases, Crohn's disease and ulcerative colitis, requires a broad understanding of disease pathophysiology and therapeutic alternatives. The goals of therapy are accurate diagnosis and timely treatment to both induce and maintain a clinical remission and improve patient quality of life. Most patients can be adequately treated using a combination or aminosalicylates, antibiotics, and corticosteroids, though many patients with Crohn's disease will require immunomodulators, such as azathioprine or 6-mercaptopurine. The development of novel biologic therapies, particularly infliximab, have dramatically improved our ability to medically manage more severe Crohn's disease and ulcerative colitis patients. This review will focus on the medical management of inflammatory bowel disease in adults.     

Progression of inflammatory bowel disease in China

The epidemiology and phenotype of inflammatory bowel disease (IBD) in the Chinese population is not well-known. We performed a comprehensive search of the Chinese biomedical literature database from 1989 to 2007 using the following key words: inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD). The investigation of hospitalized IBD patients from 1990 to 2003 was also carried out in 23 medical centers of 11 cities over China. There are some notable epidemiological and phenotypical differences between Chinese IBD and Caucasian IBD, including a lack of familial clustering, male predominance, a relatively later onset of the illness with no second peak age occurrence after 50 years old, a milder clinical course, less extra-intestinal manifestations and complications, and less fistulous and peri-anal complications in Chinese CD. The data indicate an increased incidence of IBD in China with many complicated clinical problems, which offers potential opportunities to study the disease prospectively and identify the etiological factors, leading also to the better management of this disease in China.