Crohn's-like reaction in diverticular disease

Background—Diverticulitis and Crohn's diseaseaffecting the colon occur at similar sites in older individuals, and incombination are said to carry a worse prognosis than either disease inisolation. It is possible that diverticulitis may initiate inflammatorychanges which resemble Crohn's disease histologically, but do notcarry the clinical implications of chronic inflammatory bowel disease.
Aims—To evaluate histological features andclinical outcome in individuals initially diagnosed histologically ashaving both Crohn's colitis and diverticulitis.
Patients—Eleven consecutive individuals having acolonic resection showing histological features of both Crohn'sdisease and diverticulitis.
Methods—Retrospective review of histologicalspecimens, case notes, and discharge letters.
Results—In nine patients, the Crohn's-likereaction was confined to the segment bearing diverticula. They had noclinical evidence of Crohn's disease.
Conclusion—A Crohn's-like inflammatory responsecan be a localised reaction to diverticulitis and does not necessarilyindicate chronic inflammatory bowel disease.

Keywords:Crohn's disease; diverticulitis; colitis; histology

     

Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role

^a Service d'Hépato-Gastroentérologie, Hôpital Huriez, ^b Laboratoire de Parasitologie-Mycologie, ^c Service d'Epidémiologie et de Santé Publique, CH et U Lille, ^d Département d'Hématologie-Immunologie-Cytogénétique, CH Valenciennes, France, ^e Division of Gastroenterology and the UCLA Inflammatory Bowel Disease Center, Department of Medicine, UCLA School of Medicine, Los Angeles, California, USA

Correspondence to: Dr J-FColombel, Clinique des Maladies de l'Appareil Digestif et de la Nutrition, Hôpital Huriez, CH et U Lille, 59037 Lille, France.

Accepted for publication 19 January 1998

Background—Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) are a well recognised marker for ulcerative colitis. Antibodies to oligomannosidic epitopes of the yeast Saccharomyces cerevisiae (ASCA) are a new marker associated with Crohn's disease.
Aims—To assess the value of detecting pANCA and/or ASCA for the diagnosis of ulcerative colitis and Crohn's disease.
Methods—Serum samples were obtained from 100 patients with Crohn's disease, 101 patients with ulcerative colitis, 27 patients with other miscellaneous diarrhoeal illnesses, and 163 healthy controls. Determination of pANCA and ASCA was performed using the standardised indirect immunofluorescence technique and an ELISA, respectively.
Results—The combination of a positive pANCA test and a negative ASCA test yielded a sensitivity, specificity, and positive predictive value of 57%, 97%, and 92.5% respectively for ulcerative colitis. The combination of a positive ASCA test and a negative pANCA test yielded a sensitivity, specificity, and positive predictive value of 49%, 97%, and 96% respectively for Crohn's disease. Among patients with miscellaneous non-inflammatory bowel disorders, three were ASCA positive and two were pANCA positive. One control was ASCA positive. The presence of ASCA in patients with Crohn's disease was associated with small bowel involvement.
Conclusion—ASCA and pANCA are strongly associated with Crohn's disease and ulcerative colitis, respectively. Combination of both tests could help the diagnosis of inflammatory bowel disease.
(GUT 1998;:788-791)

Keywords: Crohn's disease;  ulcerative colitis;  antineutrophil cytoplasmic autoantibodies;  anti-Saccharomyces cerevisiae mannan antibodies

     

Bone mineral density and nutritional status in children with chronic inflammatory bowel disease

Background—Osteoporosis has been reported inadult patients with inflammatory bowel disease.
Aims—To evaluate bone mineral density (BMD),nutritional status, and determinants of BMD in children withinflammatory bowel disease.
Patients—Fifty five patients (34 boys and 21 girls, age range 4-18) were studied; 22 had Crohn's disease and 33 ulcerative colitis.
Methods—Lumbar spine and total body BMD, and bodycomposition were assessed by dual energy x rayabsorptiometry (DXA). Results were expressed as standard deviationscores (SDS). Lean body mass was also assessed by bioelectricalimpedance analysis (BIA). Yearly measurements during two years wereperformed in 21patients.
Results—The mean SDS of lumbar spine BMD andtotal body BMD were significantly lower than normal (−0.75 and−0.95, both p<0.001). Height SDS and body mass index SDS were alsodecreased. The decrease in BMD SDS could not be explained by delay inbone maturation. The cumulative dose of prednisolone correlatednegatively with lumbar spine BMD SDS (r=−0.32, p<0.02).Body mass index SDS correlated positively with total body BMD SDS(r=0.36, p<0.02). Patients with Crohn's disease hadsignificantly lower lumbar spine and total body BMD SDS than patientswith ulcerative colitis, even after adjustment for cumulative dose ofprednisolone. In the longitudinal data cumulative dose of prednisolonebetween the measurements correlated negatively with the change inlumbar spine and total body BMD SDS. Lean tissue mass measured by DXAhad a strong correlation with lean body mass measured by BIA(r=0.98).
Conclusions—Children with inflammatory boweldisease have a decreased BMD. Children with Crohn's disease have ahigher risk of developing osteopaenia than children with ulcerativecolitis. Corticosteroid therapy and nutritional status areimportant determinants of BMD in these patients.

Keywords:bone mineral density; inflammatory bowel disease; children; nutritional status; corticosteroid treatment; bodycomposition

     

Visualising E-selectin in the detection and evaluation of inflammatory bowel disease

Background—Vascular endothelial E-selectin expression is induced by proinflammatory cytokines andcontributes to accumulation of leucocytes in tissues.
Aims—To investigate the role ofE-selectin in inflammatory bowel disease (IBD).
Methods—E-selectin expression wasassessed in patients with ulcerative colitis and Crohn's disease bymeasuring the concentration of circulating soluble E-selectin(sE-selectin) using ELISA, by immunohistochemistry of colonic biopsyspecimens, and by abdominal immunoscintigraphy after injectingradiolabelled F(ab')₂ fragment of a monoclonalanti-E-selectin antibody. The value of scintigraphy usinganti-E-selectin was judged by a prospective comparative study ofautologous leucocyte scanning and E-selectin antibody scanning in 17 patients with IBD.
Results—Circulating sE-selectin waselevated in patients with clinically active disease. Tissue expressionof E-selectin was enhanced in patients with active inflammation, withweak or absent expression in inactive disease and healthy controls.In-111 labelled anti-E-selectin scintiscans were compared with Tc-99mlabelled leucocyte scans performed 24 hours earlier. Twelve patientshad areas of active inflammation on leucocyte scan while 11 patients had positive E-selectin scans. The results of the two scans were concordant in 14 patients, with those positive for both (10/17) showingsimilar disease localisation and extent.
Conclusions—Tissue E-selectinand circulating sE-selectin are increased during active inflammatorybowel disease. Anti-E-selectin imaging with radiolabelled monoclonalantibody identified areas of inflammation in Crohn's disease andulcerative colitis. The technique should prove useful clinically foridentifying the site and extent of disease.

Keywords:E-selectin; inflammatory bowel disease; Crohn'sdisease; ulcerative colitis

     

Factors affecting splanchnic haemodynamics in Crohn's disease: a prospective controlled study using Doppler ultrasound

Background—Current knowledge on splanchnichaemodynamics in Crohn's disease is limited.
Aims—To investigate which features of Crohn'sdisease affect splanchnic haemodynamics, and to establish whetherportal vein (PV) and superior mesenteric artery (SMA) blood supplyreflects clinical or biochemical activity of Crohn's disease.
Methods—Seventy nine patients with Crohn'sdisease and 40 controls were evaluated by Doppler ultrasound (US). Themean velocity of PV and SMA flow, the volume of blood flow of the PVand SMA, and the resistance index of SMA were studied. A series ofclinical, biochemical, and US variables including Crohn's diseaseactivity index, serum C reactive protein concentrations, diseaseduration and its anatomical location, smoking habits, abdominalcomplications, and current medical therapy, as well as the maximumbowel wall thickness as measured by US, were determined. The relationbetween PV and SMA blood flow and these variables was assessed byunivariate and multivariate analysis.
Results—Patients with Crohn's disease hadsignificantly higher PV and SMA flow and a lower SMA resistance indexthan controls. Stepwise multiple regression analysis identified bowelwall thickness and location of the disease as the main predictivevariables of both PV and SMA blood flow variation, accounting for 36%and 45% of their variability, respectively. No relation was foundbetween splanchnic haemodynamics and disease activity.
Conclusion—A hyperdynamic mesenteric circulationdoes exist in Crohn's disease; however splanchnic blood flow does notreflect the clinical or biochemical activity of the disease, but seems to be linked more to other Crohn's disease characteristics, such asmaximum bowel thickness and anatomical location.

Keywords:Crohn's disease; Doppler ultrasound; splanchnicblood flow

     

Incidence of Crohn's disease in Stockholm County 1955-1989

Aim—To evaluate the incidence of Crohn'sdisease in Stockholm County between 1955 and 1989.
Methods—A cohort of 1936 patients withCrohn's disease was retrospectively assembled. Incidence rates andchanges in disease distribution were assessed.
Results—The mean increase inincidence was 15% (95% confidence intervals 12% to 18%) per fiveyear period with a mean annual incidence rate at 4.6/10⁵during the last two decades. The mean incidence for the entire studyperiod was similar for men and women. The mean age at diagnosis increased from 25 years in 1960-64 to 32 years in 1985-89, partly because of an increasing proportion of patients aged at least 60 yearsat diagnosis. The proportion of patients with colonic Crohn's diseaseat the time of diagnosis increased from 15% to 32% (17% difference;95% confidence intervals 12% to 23%) whereas the proportion ofpatients with ileocaecal disease decreased from 58% to 41% (17%difference; 95% confidence intervals 10% to 24%) during the studyperiod. Elderly patients had a higher proportion of small bowel diseaseand a lower proportion of ileocolonic disease compared with the youngerpatients.
Conclusion—The incidence rate ofCrohn's disease in Stockholm has stabilised at 4.6/10⁵ andthe proportion of elderly patients has increased during a 35 yearperiod. Colonic Crohn's disease has increased in frequency with areciprocal decrease in ileocaecal disease.

Keywords:Crohn's disease; inflammatory bowel disease; incidence; epidemiology

     

Energy expenditure and body composition in children with Crohn's disease: effect of enteral nutrition and treatment with prednisolone

Background—Malnutrition and growth retardation arecommon complications of Crohn's disease in children. The contributionof resting energy expenditure (REE) to malnutrition is unclear.
Aims—To characterise the REE and body compositionin children with Crohn's disease and compare them with normal controlsand patients with anorexia nervosa; to compare the effects ofprednisolone and enteral nutrition on energy expenditure and body composition.
Subjects—Twenty four children with Crohn'sdisease, 19 malnourished females with anorexia nervosa, and 22 healthycontrol subjects were studied.
Methods—In children with Crohn's diseasemeasurements were done when the disease was acute and repeated at oneand three months after treatment with either prednisolone or enteralnutrition. Resting energy expenditure was measured by indirectcalorimetry and body composition by anthropometry, bioelectricalimpedance analysis, total body potassium,H₂¹⁸O, and bromide space studies.
Results—Body weight and ideal body weight weresignificantly lower in patients with Crohn's disease than in healthycontrols. Lean tissue was depleted and there was an increase inextracellular water. Per unit of lean body mass, there was nodifference between REE in patients with Crohn's disease and controls,whereas patients with anorexia nervosa had significantly reduced REE.With enteral nutrition all body compartments and REE increasedsignificantly (p<0.001). In a subgroup of age-matched men there was asignificant increase in height after three months of enteral nutritioncompared with prednisolone (p<0.01). Those treated with steroids didnot show a significant change in height but did show an increase in allbody compartments. However, intracellular water as well as lean bodymass accretion were significantly higher in the enteral nutrition groupthan in the prednisolone group.
Conclusions—Despite being malnourished, childrenwith Crohn's disease fail to adapt their REE per unit of lean bodymass. This might be a factor contributing to their malnutrition. Lean tissue accretion is higher in patients treated with enteral nutrition than in those treated with prednisolone.

Keywords:Crohn's disease; resting energy expenditure; bodycomposition; anorexia nervosa; prednisolone; enteral nutrition

     

Impaired splenic function and tuftsin deficiency in patients with intestinal failure on long term intravenous nutrition

Background—Reticuloendothelial system function isimpaired in humans receiving lipid regimens.
Aims—To evaluate the effects of long termadministration of long chain triglyceride emulsions onreticuloendothelial system function.
Methods—Splenic function and tuftsin activitywere measured in 20 patients on intravenous nutrition for intestinalfailure, 20 patients with Crohn's disease who were not receivingintravenous nutrition, and 50 healthy controls.
Results—Pitted red cells counts in patientson intravenous nutrition (8.0%) were significantly higher (p<0.001)than in healthy controls (0.6%) and in patients with Crohn's disease(0.9%). No difference was found between healthy controls and patientswith Crohn's disease. There was a correlation (r=0.50;p<0.03) between percentage of pitted red cells and duration ofintravenous nutrition. Tuftsin activity was significantly reduced inthe intravenous nutrition patient group (6%) compared with bothdisease controls (16.5%, p<0.01) and healthy volunteers (17.8%,p<0.001) . An inverse correlation between tuftsin activity and pittedred cell percentage was found in the patients on intravenous nutrition(rs =−0.44, p<0.05). No relation was foundin the patients on intravenous nutrition between pitted red cellpercentage or tuftsin activity and type of disease, percentage of idealbody weight, residual length of small intestine, or administration(quantity and frequency) of lipid emulsion. Eight patients onintravenous nutrition had serious infections within the previous 12months.
Conclusions—Patients with a short bowel treatedwith long term intravenous nutrition have impaired splenic function,reduced tuftsin activity, and an increased risk of infection.

Keywords:splenic function; hyposplenism; tuftsin; homeparenteral nutrition; short bowel syndrome

     

Detection of anti-colon antibodies in inflammatory bowel disease using human cultured colonic cells

Background—Investigationof anti-colon antibodies may be simplified if a sensitive method andhomogeneous source of antigen were available.
Aims—To examine theanti-colon antibody response using human colonic carcinoma cell linesas antigen.
Subjects—Patients withinflammatory bowel disease and other gastrointestinal disorders andhealthy controls were studied.
Methods—Comparativeenzyme linked immunosorbent assays (ELISAs) were performed to assessthe value of whole Caco-2, HT-29, and LS-180 cells as antigen. Theantigenic determinants of the immune response were characterised bywestern blot analysis.
Results—Serademonstrated immunoreactivity against each of the cell lines, butdifferent epitopes were recognised. Applying whole Caco-2 cells asantigen in an ELISA, the prevalence of anti-colon antibodies wassignificantly greater in patients with ulcerative colitis (36%) thanCrohn's disease (13%), other gastrointestinal disorders (13%) andhealthy controls (0) (p<0.05). The immune response was not associatedwith one predominant antigen.
Conclusions—Fixedwhole cell ELISA is a simple and feasible method for studying theanti-colon antibody response. This response is non-specific, beingdirected against multiple antigens, and is likely to be anepiphenomenon of inflammatory bowel disease, more so for ulcerativecolitis than Crohn's disease.

Keywords:anti-colon antibodies; inflammatory boweldisease

     

Appendicectomy, childhood hygiene, Helicobacter pylori status, and risk of inflammatory bowel disease: a case control study

Aims—To examine the relation between inflammatorybowel disease and appendicectomy, childhood domestic hygiene, andHelicobacter pylori infection.
Methods—Case control study involving 213 patientswith ulcerative colitis, 110 with Crohn's disease, and 337 controlshaving elective surgery.
Results—Nine patients with ulcerative colitis(4.5%) reported a previous appendicectomy compared with 57 controls(19%) (odds ratio (OR) 0.20, 95% confidence interval (CI) 0.1-0.4,p<0.0001). The inverse association was unaffected by excludingoperations performed after the age of onset of ulcerative colitis andwas stronger for appendicectomy performed before age 20 (OR 0.14). Noassociation with appendicectomy was found for Crohn's disease and noassociations with tonsillectomy for either disease. The availability ofa fixed hot water supply in early childhood (before age 11) wasassociated with Crohn's disease (OR for hot water not always versusalways available 0.56, 95% CI 0.3-0.9, p=0.02) but not withulcerative colitis. No other aspect of domestic hygiene before or afterage 11 was associated with either Crohn's disease or ulcerativecolitis. Although H pylori seroprevalence was positively associated with overcrowding (p<0.001) and the absence of running hotwater in childhood it was not associated with the presence of eitherCrohn's disease or ulcerative colitis. H pyloriseroprevalence was no lower in patients who had been exposed tosulphasalazine than in controls or those not exposed.
Conclusions—Our findings confirm the stronginverse association between previous appendicectomy and the developmentof ulcerative colitis and suggest that the protective effect is greaterfor appendicectomy performed in childhood.

Keywords:inflammatory bowel disease; appendicectomy; tonsillectomy; childhood hygiene; Helicobacter pylori; sulphasalazine

     

Search for Mycobacterium paratuberculosis DNA in orofacial granulomatosis and oral Crohn's disease tissue by polymerase chain reaction

Background—Although intestinalCrohn's disease has long been suspected to have amycobacterial cause, possible mycobacterial involvement in orofacialgranulomatosis (OFG) and oral lesions of Crohn's disease has not yetbeen investigated.
Aims—As the slow growingMycobacterium paratuberculosis has been implicated in theaetiology of intestinal Crohn's disease, the potential involvement ofthis mycobacterial species in OFG and oral lesions of Crohn's diseasewas investigated.
Patients—To attempt detectionof the organism in OFG and oral Crohn's disease tissue samples, apolymerase chain reaction (PCR) assay was used on archival formalinfixed, paraffin wax embedded oral tissue sections from 30 patients withOFG, seven with Crohn's disease, and 12 normal controls.
Methods—The PCR assay used wasbased on primers targeting the 5' region of the multicopy IS900 DNAinsertion element of the M paratuberculosis genome. Inorder to achieve maximum sensitivity, two rounds of PCR were carriedout and amplicons confirmed by Southern blot hybridisation to adigoxigenin labelled IS900 DNA probe.
Results—None of the OFG andoral lesions of Crohn's disease samples were positive forM paratuberculosis and all normal controls were also negative.
Conclusions—These results suggestthat M paratuberculosis may not be a major aetiologicalagent in OFG or oral Crohn's disease lesions, although the use ofparaffin wax embedded tissue as opposed to fresh tissue as a samplesource could underestimate the true prevalence of the organism.

Keywords:oral Crohn's disease; Mycobacteriumparatuberculosis; orofacial granulomatosis; polymerase chainreaction

     

Poor diagnostic value of colonic CD44v6 expression and serum concentrations of its soluble form in the differentiation of ulcerative colitis from Crohn's disease

Background—Increased expression ofCD44v6 on colonic crypt epithelial cells in ulcerative colitis has beensuggested as a diagnostic tool to distinguish ulcerative colitis fromcolonic Crohn's disease.
Aims—To investigate colonicCD44v6 expression and serum concentrations of soluble CD44v6 (sCD44v6)in patients with ulcerative colitis and Crohn's disease.
Methods—Colonic biopsy samples wereobtained from 16 patients with ulcerative colitis, 13 with ileocolonicCrohn's disease, and 10 undergoing polypectomy. Serum samples wereobtained from 15 patients with active ulcerative colitis, 20 withactive Crohn's disease, and 20 healthy donors. Colonic CD44v6expression was evaluated immunohistochemically by monoclonal antibody2F10 and the higher affinity monoclonal antibody VFF18. Serum sCD44v6concentrations were measured by ELISA.
Results—2F10 stained colonicepithelium of inflamed ulcerative colitis and Crohn's disease samplesin 80% and 40% of cases, respectively, and VFF18 in 95% and 87%,respectively. Both monoclonal antibodies displayed a sensitivity andspecificity of 60% and 87% to differentiate ulcerative colitis fromcolonic Crohn's disease. Serum concentrations of sCD44v6 were lower inpatients with ulcerative colitis (median 153 ng/ml; interquartile range(IQR) 122-211) compared with Crohn's disease (219; IQR 180-243) andhealthy donors (221; IQR 197-241 (p=0.002)). Its sensitivity andspecificity to discriminate ulcerative colitis from Crohn's diseasewas 75% and 71%, respectively.
Conclusion—Colonic CD44v6 and serumsCD44v6 concentrations do not facilitate reliable differentialdiagnosis between ulcerative colitis and Crohn's disease.

Keywords:CD44 variant 6; differential diagnosis; immunohistochemistry; soluble CD44v6

     

Monozygotic twins with Crohn's disease and ulcerative colitis: a unique case report

Background—A large number of monozygotic anddizygotic twin pairs with inflammatory bowel disease have beenreported. To date no twin pair has developed phenotypically discordantinflammatory bowel disease. This case report is the first documentedoccurrence of discordant inflammatory bowel disease occurring inmonozygotic twins.
Case report—Twenty two year old identical maletwins presented within three months of each other with inflammatorybowel disease that proved to be discordant in overall disease type,disease distribution, clinical course, and histopathological findings. Twin 1 developed a severe pancolitis necessitating total colectomy while twin 2 developed a predominantly distal patchy colitis with frequent granulomas, controlled by aminosalicylates. Twin 1 was antineutrophil cytoplasmic antibody (ANCA) negative at the time oftesting while twin 2 (Crohn's disease) was ANCA positive.Significantly, the twins possessed the HLA type DR3-DR52-DQ2 previouslyassociated with extensive colitis.
Conclusion—This case report confirms the importantrole played by genetic factors in the development of inflammatory bowel disease. It also highlights the crucial role of undeterminedenvironmental agents in dictating disease expression and phenotype.

Keywords:monozygotic twins; ulcerative colitis; Crohn'sdisease; inflammatory bowel disease

     

Imbalance of the interleukin 1 system in colonic mucosa—association with intestinal inflammation and interleukin 1 receptor agonist genotype 2

Background—Interleukin 1 (IL-1) α and β arepotent cytokines which play key roles in inflammation. They arecontrolled by IL-1 receptor antagonist (IL-1ra).
Aims—To investigate the influence of mucosalinflammation and IL-1ra genotype on the IL-1ra:IL-1 balance.
Patients and methods—IL-1α, IL-1β, and IL-1rawere measured by enzyme linked immunosorbent assay (ELISA) in biopsyspecimens taken from inflamed and non-inflamed colon of 60 patientswith Crohn's disease (CD), 34 with ulcerative colitis (UC), 15 inflammatory controls, and 103 non-inflamed controls. IL-1ra genotypewas determined by polymerase chain reaction and gel electrophoresis.
Results—IL-1α and IL-1β were significantlyincreased in inflamed mucosa in inflammatory bowel disease (IBD) (CD:53.5 (22.4) and 409.9 (118.7) pg/mg protein, respectively; UC: 18.9 (6.8) and 214.5 (78.2) pg/mg, respectively) and non-IBD patients (19.2(7.4) and 281.4 (121.0) pg/mg, respectively; p<0.0001) compared withnormal controls (2.8 (0.6) and 30.6 (5.6) pg/mg, respectively). In CDIL-1α and β were also significantly increased in non-inflamed mucosa (6.1 (1.3) pg/mg and 88.7 (17.4) pg/mg, respectively;p<0.0012). IL-1ra:(IL-1α+β) ratios were significantly decreased ininflamed mucosa of patients with CD (182 (45); p<0.0001), UC (425 (136); p=0.0018) and without IBD (221 (76); p<0.0001), and innon-inflamed mucosa in CD (369 (149); p<0.0001) compared with normalcontrols (1307 (245); p<0.0001). Patients with IL-1ra genotype 2 hadslightly but significantly reduced mucosal IL-1ra concentrations(p=0.003). The greatest difference was seen in colonic biopsy specimensfrom patients with inflamed Crohn's disease.
Conclusion—Mucosal inflammation can modulate thebalance of the IL-1:IL-1ra system in colonic mucosa.

Keywords:interleukin 1; interleukin 1 receptor antagonist; inflammatory bowel disease; Crohn's disease; mucosal inflammation; genotype

     

Transthoracic ultrasonic visualisation of coronary aneurysm, stenosis, and occlusion in Kawasaki disease

OBJECTIVE—To determine the sensitivity and specificity of our transthoracic echocardiographic technique using high frequency (7.5 MHz) transducers for identification of the presence and type of coronary artery disease in patients with Kawasaki disease.
DESIGN—The results of the prospective echocardiographic study in each of seven segments of the four major coronary arteries were compared with the selective coronary angiograms.
SETTING—Kitasato University Hospital.
SUBJECTS—60 patients with Kawasaki disease, ranging in age from 8.0 months to 22 years (median, 6.0 years).
RESULTS—Adequate echocardiographic images were obtained in 397 (95%) of 420 coronary segments. Coronary angiography showed the presence of coronary aneurysms in 87 segments and stenosis or occlusion in 28. The overall sensitivity and specificity of cross sectional echocardiography for correctly identifying coronary aneurysms were 95% and 99%, respectively; for correctly identifying coronary stenosis or occlusion the values were 85% and 98% for the right coronary artery, and 80% and 97% for the left anterior descending coronary artery. Agreement on the presence or absence of coronary aneurysms and obstructive lesions on echocardiograms between the two observers was 1.0 and 0.98, respectively.
CONCLUSIONS—Echocardiography may provide a non-invasive means of identifying the presence and type of coronary artery disease in patients with Kawasaki disease.


Keywords: Kawasaki disease; coronary artery aneurysm; coronary artery stenosis; echocardiography     

Controlled trial of antituberculous chemotherapy in Crohn's disease: a five year follow up study

Background—It has been suggested thatMycobacterium paratuberculosis is the cause of Crohn'sdisease. In a previous report the immediate effect of two yearstreatment with antituberculous chemotherapy showed no clinical benefit.
Aims—To assess both the immediate and longer termeffect of treatment on the disease.
Methods—Patients were followed for five yearsfrom their date of entry to the study. One hundred and thirty patientsentered the initial study, and of these 111 (81%) were followed regularly.
Results—Overall, there was no evidence ofconsistent benefit or disadvantage from antituberculous chemotherapy inany of the assessments made, including the number of acute relapses,surgical episodes, hospital admissions, disease activity, blood tests, or medication required for Crohn's disease during the follow up period.
Conclusion—The absence of any benefit at the endof the initial two year trial period, and during the three yearsubsequent follow up, fails to support the hypothesis that mycobacteriaplay an important part in the pathogenesis of Crohn's disease, or that antituberculous chemotherapy may be of benefit.

Keywords:Crohn's disease; mycobacteria; antituberculuschemotherapy

     

Anticipation in familial Crohn's disease

Background—Offspring with a family historyof Crohn's disease have an earlier age of onset than their parents.This might be due to genetic anticipation, characterised by earlierand/or more severe disease in subsequent generations.
Aims—To investigate the possibility of geneticanticipation in affected parent-child pairs with Crohn's disease fromFrance and Belgium.
Patients and methods—In a cohort of 160 multiplyaffected families with Crohn's disease, 57 parent-first affected childpairs were detected. Clinical characteristics (age at diagnosis,disease extent, and type) of both parents and children were registered and compared.
Results—Children were younger than their parentsat diagnosis in 48/57 (84%) pairs. The median age at diagnosis was 16 years younger in children than in parents (p<0.0001). However, thedifference was related to the age at diagnosis in the parents and wasnot present in 12 parent-child pairs with an early age at diagnosis forthe parents. In most cases, disease extent and type were not consideredmore severe in children than in parents. Parental sex affected neitherage at diagnosis nor extent and type of disease in children.
Conclusion—Patients in the second affectedgeneration acquire their disease at an earlier time in life in some butnot all familial cases of Crohn's disease. Several explanationsincluding genetic anticipation and environmental factors might explainthis phenomenon.

Keywords:Crohn's disease; familial; geneticanticipation

     

Low dose oral pH modified release budesonide for maintenance of steroid induced remission in Crohn's disease

Background—The relapse rate after steroid inducedremission in Crohn's disease is high.
Aims—To test whether oral pH modified releasebudesonide (3 × 1 mg/day) reduces the relapse rate and to identifypatient subgroups with an increased risk of relapse.
Methods—In a multicentre, randomised, doubleblind study, 179 patients with steroid induced remission of Crohn'sdisease received either 3 × 1 mg budesonide (n=84) or placebo (n=95)for one year. The primary study aim was the maintenance of remission ofCrohn's disease for one year.
Results—Patient characteristics at study entrywere similar for both groups. The relapse rate was 67% (56/84) in thebudesonide group and 65% (62/95) in the placebo group. The relapsecurves in both groups were similar. The mean time to relapse was 93.5days in the budesonide group and 67.0 days in the placebo group. Noprognostic factors allowing prediction of an increased risk for relapseor definition of patient subgroups who derived benefit from low dosebudesonide were found. Drug related side effects were mild and nodifferent between the budesonide and the placebo group.
Conclusion—Oral pH modified release budesonide ata dose of 3 × 1 mg/day is not effective for maintaining steroidinduced remission in Crohn's disease.

Keywords:budesonide; Crohn's disease; maintenance ofremission

     

Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease

Background—Reactive oxygen species contribute totissue injury in inflammatory bowel disease (IBD). The tripeptideglutathione (GSH) is the most important intracellular antioxidant.
Aims—To investigate constituent amino acid plasmalevels and the GSH redox status in different compartments in IBD withemphasis on intestinal GSH synthesis in Crohn's disease.
Methods—Precursor amino acid levels were analysedin plasma and intestinal mucosa. Reduced (rGSH) and oxidisedglutathione (GSSG) were determined enzymatically in peripheral bloodmononuclear cells (PBMC), red blood cells (RBC), muscle, and innon-inflamed and inflamed ileum mucosa. Mucosal enzyme activity ofγ-glutamylcysteine synthetase (γGCS) and γ-glutamyl transferase(γGT) was analysed. Blood of healthy subjects and normal mucosa froma bowel segment resected for tumour growth were used as controls.
Results—Abnormally low plasma cysteine and cystinelevels were associated with inflammation in IBD (p<10^-4).Decreased rGSH levels were demonstrated in non-inflamed mucosa (p<0.01) and inflamed mucosa (p=10^-6) in patients withIBD, while GSSG increased with inflammation (p=0.007) compared withcontrols. Enzyme activity of γGCS was reduced in non-inflamed mucosa(p<0.01) and, along with γGT, in inflamed mucosa(p<10^-4). The GSH content was unchanged in PBMC, RBC, and muscle.
Conclusions—Decreased activity of key enzymesinvolved in GSH synthesis accompanied by a decreased availability ofcyst(e)ine for GSH synthesis contribute to mucosal GSH deficiency inIBD. As the impaired mucosal antioxidative capacity may further promote oxidative damage, GSH deficiency might be a target for therapeutic intervention in IBD.

Keywords:Crohn's disease; ulcerative colitis; glutathione; amino acids; γ-glutamylcysteine synthetase; mucosa

     

Associations between different forms of gastro-oesophageal reflux disease

Abstract
Aims—To study the epidemiology and naturalhistory of gastro-oesophageal reflux disease (GORD).
Methods—Retrospective cohort study involving all172 hospitals of the Department of Veterans Affairs. A total of194 527 patients with GORD were followed between 1981 and 1994. Distribution of oesophagitis, oesophageal ulcer, oesophageal stricture,strictured hiatus hernia, hiatus hernia, and pyrosis by age, sex, andethnicity were determined. The comorbid occurrence of various forms ofGORD in identical patients was analysed by an age and race standardised morbidity ratio. The population of all hospitalised veterans was usedfor comparison.
Results—Severe forms of GORD associated withoesophageal erosions, ulcers, or strictures, affected elderly, white,male patients more often than their corresponding opposite demographicgroup. All forms of GORD clustered in the same patient population; on average, any form of GORD was 10 times more likely to occur in apatient with another form of GORD than without. The highest morbidityratio (22) was found in oesophageal ulcer and stricture. About onethird of all patients with oesophageal erosions, ulcers, or stricturesalso had hiatus hernia; 46% of patients with hiatus hernia werediagnosed as having other forms of GORD. While one third of alloesophageal strictures appeared in patients without other forms of GORDdiagnosed at any time, oesophageal ulcers were always associated withsome other form of GORD. No clear cut progression in different forms ofGORD was found.
Conclusions—Older age, male sex, and whiteethnicity are risk factors in the development of severe forms of GORD.The most severe grade of GORD is reached at the onset of the disease.

Keywords:epidemiology of GORD; erosive oesophagitis; oesophageal stricture; oesophageal ulcer; hiatus hernia; naturalhistory; pyrosis; reflux oesophagitis