Doppler sonography in inflammatory bowel disease

The course of chronic inflammatory bowel diseases is highly variable and prediction of relapse remains difficult. Doppler sonography is a newer, non-invasive method to assess the hyperdynamic splanchnic blood flow that is characteristic of acute inflammation. Its role in the analysis of disease activity is still limited and its application restricted to specialized units. However, improved spatial resolution by power Doppler ultrasound, with or without the use of contrast agents, allows a very early detection of mucosal and transmural inflammatory lesions. Still more important, the repeated quantification of mesenteric blood flow enables the prediction of relapse at six months after steroid-induced remission. Future studies should clarify whether the combined application of available methods will allow a more calculated and finally more effective therapy.     

Doppler sonography in the diagnosis of inflammatory bowel disease

Over the past few years, thanks to its ability to reveal neovascularization and inflammatory hyperemia, Doppler sonography has proved to be a valuable method for the assessment of disease activity in inflammatory bowel disease. Hypervascularization has been detected by Doppler imaging both in splanchnic vessels, in terms of flow volume and velocity, or resistance and pulsatility index on spectral analysis, and in small vessels of the affected bowel wall in terms of vessel density. In particular, power Doppler has been shown to be a highly sensitive method for evaluating the presence of flow in vessels that are poorly imaged by conventional color Doppler, and in detecting internal fistulas complicating Crohn's disease. Recently, the use of ultrasound contrast agents, such as Levovist, has been shown to improve the image quality of color Doppler by increasing the backscattered echoes from the desired regions, thus making it possible to better monitor the response to treatment and discriminate between active inflammatory and fibrotic bowel wall thickness in Crohn's disease. Additionally, Levovist-enhanced power Doppler sonography has proved to be highly sensitive and specific in the detection of inflammatory abdominal masses associated with Crohn's disease. In clinical practice, used in combination with second harmonic imaging and new generations of stable contrast agents, Doppler sonography appears to be a non-invasive and effective diagnostic tool in the diagnosis and follow-up of Crohn's disease and ulcerative colitis.     

Non-invasive investigation of inflammatory bowel disease

The assessment of inflammatory activity in intestinal disease in man can be done using a variety of different techniques. These range from the use of non-invasive acute phase inflammatory markers measured in plasma such as C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) (both of which give an indirect assessment of disease activity) to the direct assessment of disease activity by intestinal biopsy performed during endoscopy in association with endoscopic scoring systems. Both radiology and endoscopy are conventional for the diagnosis of inflammatory bowel disease (IBD). However these techniques have severe limitations when it comes to assessing functional components of the disease such as activity and prognosis. Here we briefly review the value of two emerging intestinal function tests. Intestinal permeability, although ideally suited for diagnostic screening for small bowel Crohn's disease, appears to give reliable predictive data for imminent relapse of small bowel Crohn's disease and it can be used to assess responses to treatment. More significantly it is now clear that single stool assay of neutrophil specific proteins (calprotectin, lactoferrin) give the same quantitative data on intestinal inflammation as the 4 day faecal excretion of 111Indium labelled white cells. Faecal calprotectin is shown to be increased in over 95% of patients with IBD and correlates with clinical disease activity. It reliably differentiates between patients with IBD and irritable bowel syndrome. More importantly, at a given faecal calprotectin concentration in patients with quiescent IBD, the test has a specificity and sensitivity in excess of 85% in predicting clinical relapse of disease. This suggests that relapse of IBD is closely related to the degree of intestinal inflammation and suggests that targeted treatment at an asymptomatic stage of the disease may be indicated.     

Changes in splanchnic hemodynamics in inflammatory bowel disease. Non-invasive assessment by Doppler ultrasound flowmetry.

An increase in splanchnic blood flow in both arterial and venous beds has been demonstrated in inflammatory bowel disease (IBD) by means of angiographic and scintigraphic studies. Doppler ultrasound (US) enables a non-invasive evaluation of splanchnic arterial inflow in the superior mesenteric artery (SMA) and of venous outflow in the portal vein. The aim of this study was to assess the role of Doppler US in detecting changes in the hemodynamic variables measured in patients with IBD. Forty-five patients with IBD were studied, including 22 with Crohn's disease (CD) and 23 with ulcerative colitis (UC), and compared with 45 matched normal subjects. The mean velocity of portal flow (Vmean) and the resistance index (RI) of the SMA were evaluated by Doppler US. In CD the Vmean of portal flow was significantly higher in patients with active disease than in controls (p less than 0.001) and patients with inactive disease (p less than 0.001). The RI of the SMA was significantly lower in active disease than in controls (p less than 0.005), but no significant difference was noted between active and inactive CD. Also in UC, the Vmean of portal flow was significantly higher in patients with active disease than in controls (p less than 0.01) and patients with inactive disease (p less than 0.05). The RI of the SMA was significantly lower in active disease than in controls (p less than 0.005) and in patients with inactive disease (p less than 0.005). Doppler follow-up studies were carried out in 10 patients after initiation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of criteria for the activity of Crohn's disease by power Doppler sonography

BACKGROUND/AIM: In recent years, power Doppler sonography has been proposed as a method to assess disease activity in patients with Crohn's disease. The aim of this prospective study was to evaluate diagnostic criteria for power Doppler sonography by blinded comparison with ileocolonoscopy. METHODS: Twenty-two patients with confirmed Crohn's disease were prospectively investigated with B-mode and power Doppler sonography (HDI 5000, Philips Ultrasound) as well as ileocolonoscopy. Sonography was performed within 3 days before endoscopy. All procedures were performed by experienced examiners who were blinded to the clinical data and other results. Defined ultrasound parameters (bowel wall thickness, vascularization pattern) were used to determine a sonographic score of the activity. The degree of activity was scored from 1 (none) to 4 (high) by both ultrasound and ileocolonoscopy (pattern, extent of typical lesions). For each patient all segments of the colon and the terminal ileum were evaluated by both ultrasound and endoscopy. The weighted kappa test was used (StatXact software) for statistical analysis. RESULTS: In total, 126 bowel segments were evaluated by both ultrasound and endoscopy. The study showed a high concordance of power Doppler sonography and ileocolonoscopy (weighted kappa by region: sigmoid colon: 0.81; transverse colon: 0.78; ascending colon: 0.75; cecum: 0.84; terminal ileum: 0.82). Highest concordance was found in the descending colon (weighted kappa: 0.91; 95% CI: 0.83-0.98). CONCLUSIONS: Combination of B-mode and power Doppler sonography has a high accuracy in the determination of disease activity in Crohn's disease when compared to ileocolonoscopy. The diagnostic criteria established in this study can be useful for the evaluation of inflammatory bowel diseases by ultrasound.     

Assessment of disease activity in inflammatory bowel diseases: Non-invasive biomarkers and endoscopic scores

Inflammatory bowel diseases (IBD) comprise two major forms: Crohn’s disease and ulcerative colitis. The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinations. In addition, the discovery of biomarkers has significantly improved the diagnosis and management of IBD. Several potential genetic, serological, fecal, microbial, histological and immunological biomarkers have been proposed for IBD, and they have been evaluated for clinical routine and clinical trials. Ileocolonoscopy, especially with biopsy collection, has been considered the standard method to diagnose IBD and to assess clinical activity of the disease, but it is limited to the colon and terminal ileum and is considered invasive. For this reason, non-invasive biomarkers are necessary for this type of chronic inflammatory disease, which affects mostly young individuals, as they are expected to have a long follow-up.     

Determining disease activity in inflammatory bowel disease

To provide a stronger relationship between clinical assessment of disease activity and laboratory measurements, we studied hemoglobin concentrations, sedimentation rates, and the serum levels of albumin and of seromucoids in 86 patients; first when seriously ill with either ulcerative colitis or Crohn's disease, and then again when they were well. Only albumin and seromucoids were separated clearly in the two states: hemoglobin and sedimentation rates showed significant overlap. Paired correlation tests between 10 laboratory variables in 149 patients with Crohn's disease of varying severity revealed a highly significant correlation between seromucoids and albumin (r = 0.71). Both variables correlated with six others, but at lower levels. Processing the correlation matrix by factor analysis suggested that the serum levels of albumin and seromucoid are indicators of the same effect--disease activity. A simple index using only hemoglobin, albumin, and seromucoid values, was derived from this analysis, positive values indicating health and negative ill health. Serum levels of albumin and seromucoids provide the essential data to determine disease activity at routine follow-up of inflammatory bowel disease or to indicate the success or failure of therapeutic regimens, overriding any arbitrary clinical assessment.     

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.     

Clinical activity assessment in inflammatory bowel disease

Standardized methods of making and recording clinical observations of patients with inflammatory bowel disease are needed for the conduct of controlled clinical trials and for the application of the results of such trials to clinical practice. A number of attempts to develop such methods have been made since the early 1950s, and such efforts continue at present. A universally accepted and acceptable clinical instrument to measure the disease activity of either Crohn's disease or ulcerative colitis will probably never be achieved. However, if interested clinicians can agree on a basic set of observations and how to make and record them, accurate comparisons of therapeutic outcomes across time and space will become possible. Toward this goal several groups of clinicians are currently working.     

Thiol methyltransferase activity in inflammatory bowel disease

BACKGROUND: Luminal anionic sulphide may contribute to epithelial damage in ulcerative colitis. Thiol methyltransferase (TMT) governs sulphide detoxification by the colonic mucosa and circulating erythrocytes. AIMS: To measure levels of TMT activity in erythrocytes of surgically treated cases of colitis or in rectal biopsies of defined groups of colitis. PATIENTS: Venepuncture blood was obtained from 37 blood donors and 27 subjects who had previously undergone a proctocolectomy for colitis: 18 for ulcerative colitis and nine for Crohn's colitis. Rectal biopsies from 122 cases were obtained: 47 without mucosal disease, 33 post-colon resection for cancer, 14 with moderate to severe ulcerative colitis, 15 with quiescent ulcerative colitis, seven with acute Crohn's colitis, and six with radiation proctitis. METHODS: TMT activity was measured by high performance liquid chromatography with radioactive detection to measure (14)C methylmercaptoethanol formation, the reaction product of cell extracts incubated with mercaptoethanol and (14)C S-adenosylmethionine. RESULTS: Erythrocyte TMT activity of surgically treated cases of colitis was significantly elevated (p<0. 001) compared with control cases. TMT activity of rectal biopsies was significantly decreased (p<0.02) in acute but not quiescent ulcerative colitis, Crohn's colitis, or radiation colitis. CONCLUSIONS: Erythrocyte TMT activity was persistently elevated after proctocolectomy for Crohn's disease and ulcerative colitis. No primary defect of TMT activity was found in any case of unoperated colitis but mucosal activity was diminished with disease progression of ulcerative colitis. Studies of genetic control of TMT activity of erythrocytes in inflammatory bowel disease appear worthwhile.     

Circulating interferon-like activity in inflammatory bowel disease

Inflammatory bowel diseases (IBD) has been characterized as having an autoimmune background. We studied the presence of immune interferon in the sera of a small number of patients with IBD. Antiviral activity was detectable in the sera of our patients with well-controlled IBD but it was mainly weak-positive (50% inhibition of virus CPE in a dilution of 1:10 per 0.2 ml of serum). The antiviral activity varied according to the sensitivity of the cell line used. The human amnion cells Wish (81%) and the human embryonic Intestine-407 (73%) were more sensitive.     

Non-invasive evaluation of cardiac output by Doppler echocardiography

In order to evaluate Doppler echocardiography (DEC) used for cardiac output (CO) measurement, 22 patients (7 with coronary heart disease, 6 with dilatation cardiomyopathy, 5 with primary pulmonary hypertension and 4 with rheumatic heart disease) were studied. In all patients, invasive CO determination was performed by right heart catheterization, using thermodilution (T). In DEC, CO was calculated as CO = IV.S.HR, where IV was integral velocity, estimated on the basis of flow areas under planimetric curves, S was aortic root cross-section area, and HR was heart rate. A close correlation was demonstrated between DEC and T results (r-0.74). Only in one case with severe aortic atherosclerosis was there a significant difference between the data. This case excluded, the correlation becomes even closer (r-0.86). It is concluded that: 1) DEC is a valuable and precise method of CO assessment, 2) DEC may be used to monitor treatment efficacy, and 3) its limitation is aortic lesions.     

Indices of granulocyte activity in inflammatory bowel disease

In conditions with increased neutrophil production, the serum total vitamin B(12)-binding capacity (TBBC) is considered to correlate with the blood pool size of neutrophil granulocytes. The serum lysozyme, on the other hand, is a measure of neutrophil (and monocyte) turnover. The mean serum TBBC was significantly raised in patients with ulcerative colitis (range 1.23-5.51 ng/ml; mean 2.64 ng/ml) and patients with Crohn's disease (range 1.58-9.29 ng/ml; mean 2.93 ng/ml). The elevated values were shown to be due to rises in the granulocyte-secreted binding proteins, transcobalamins I and III. The TBBC was shown to rise with increasing activity of disease and to correlate roughly with the blood neutrophil granulocyte count. Patients with inflammatory bowel disease also had a significantly raised mean level of serum lysozyme (range 3.1 to 10.4 mug/ml; mean 6.8 mug/ml), but there was no correlation in individual patients between serum lysozyme and total B(12)-binding capacity. These results are taken to indicate an enlarged granulocyte pool and increased granulocyte turnover in inflammatory bowel disease.     

Depressive mood and disease activity in inflammatory bowel disease

Background and study aimSome mood disorders are more prevalent in chronic medical conditions compared with the general population. The relationship between inflammatory bowel disease (IBD) and psychiatric disorders has been raised as an area of interest for investigation. In this study, we aimed to assess the probable relationship between depression and disease activity in IBD patients in Golestan province, northeast of Iran.Patients and methodsDuring February 2008 to February 2010, 50 patients recently diagnosed as IBD cases attended the Golestan Research Center of Gastroenterology and Hepatology (GRCGH), northeast of Iran. The Simple Clinical Colitis Activity Index (SCCAI) was used to evaluate the disease activity. The Beck Depression Inventory (BDI) was used to assess the severity of depressive symptoms. Depression was assumed when the BDI score was 13 points or higher.ResultsSixteen cases (32%) had depressive characteristics. SCCAI and the Beck score were not significantly different between the two sexes. There was a non-significant correlation between SCCAI, Beck score, age and body mass index (BMI).ConclusionsWe reported a relatively high percent of depression in IBD patients, although no significant relationship was seen.     

Determination of inflammatory bowel disease activity by breath pentane analysis

PURPOSE: Quantitative determination of breath pentane, an alkane generated by peroxidation of cellular fatty acids, has been used as a noninvasive determinant of inflammation. Herein we report the first examination of the relationship between breath pentane and intestinal inflammation in humans. METHODS: Patients (N=33), either with a known history of inflammatory bowel disease (IBD) with symptoms of relapse or with no known history of but having symptoms consistent with IBD, were evaluated with indium-111-labeled leukocyte imaging to assess the presence of active inflammation. At the time of the indium scan, the exhaled breath of the patients was obtained via a collecting tube. Gas chromatography was used to quantify the pentane content, and these values were compared with graded indium scans. RESULTS: The range of breath pentane found in our population (36 determinations in 33 patients) was from 0 to 38.4 nmol/ 1 of exhaled air. For patients with negative scans, the mean pentane was 2.1 nmol/l, for intermediate scans 3.1, for positive scans 4.3, and for nonintestinal nuclide imaging 5.5 [P =0.005 by analysis of variance (ANOVA)]. CONCLUSIONS: We have previously demonstrated the correlation of breath pentane with gross and histologic evidence of intestinal inflammation in a rodent colitis model. This current study also demonstrates that pentane analysis can be correlated with inflammatory bowel disease activity in humans.     

Assessing disease activity and disease activity indices for inflammatory bowel disease

A crucial step in the development of clinical trials to determine the efficacy of various therapies for inflammatory bowel disease (IBD) has been the creation of activity indices. This article reviews the major components and operating characteristics of clinical activity indices commonly used in randomized, controlled trials of IBD therapy. In addition, the paper provides a brief overview of the developmental requirements for any new index.     

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.