Oral budesonide is as effective as oral prednisolone in active Crohn's disease

Background—The use of corticosteroids in activeCrohn's disease often becomes limited by side effects. Budesonide is apotent corticosteroid with low systemic bioavailability due to anextensive first pass liver metabolism.
Aims—To compare the efficacy and safety of twodosage regimens of budesonide and prednisolone in patients with activeCrohn's disease affecting the ileum and/or the ascending colon.
Patients and methods—One hundred and seventy eightpatients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn'sDisease Activity Index (CDAI) of 150 or less.
Results—After eight weeks of treatment, remissionoccurred in 60% of patients receiving budesonide once daily orprednisolone and in 42% of those receiving budesonide twice daily(p=0.062). The presence of glucocorticoid associated side effects wassimilar in all groups; however, moon face was more common in theprednisolone group (p=0.0005). The highest frequency of impairedadrenal function, as measured by a short ACTH test, was found in theprednisolone group (p=0.0023).
Conclusions—Budesonide CIR, administered at 9 mgonce daily or 4.5 mg twice daily, is comparable to prednisolone ininducing remission in active Crohn's disease. The single doseadministration is as promptly effective as prednisolone and representsa simpler and safer therapeutic approach, with a considerable reduction in side effects.

Keywords:adrenal function; CDAI; glucocorticoid; glucocorticoid associated side effects

     

Use of mesalazine slow release suppositories 1 g three times per week to maintain remission of ulcerative proctitis: a randomised double blind placebo controlled multicentre study

Background—Daily administration of rectalformulations of mesalazine is effective in preventing relapse ofulcerative proctitis. Maintenance of remission with lower doses wouldbe an advantage.
Aim—The efficacy of mesalazine suppositories(Pentasa) 1 g three times a week v placebo to maintainremission in patients with cryptogenetic proctitis was studied.
Methods—Ninety five patients with cryptogeneticproctitis were randomised within two weeks of remission to receive forone year or until relapse three suppositories per week of eitherPentasa (n=48) or placebo (n=47). In the case of a relapse, thepatients received one suppository/day.
Results—It was found that 25 of 48 subjectsv 18 of 47 remained in remission in the mesalazine andplacebo groups respectively. The relapse rate was lower in themesalazine group for the following time intervals: 0-90 days (19%v 38%, p=0.035), 0-180 days (29% v 54%,p=0.017), 0-270 days (38% v 60%, p=0.031), and 0-365days (48% v 62%, p=0.18). Treatment of relapse with onesuppository/day induced remission in 11 of 18 and 2 of 26 patients inthe mesalazine and placebo groups respectively (p=0.001). Overall, 61%v 28% patients remained in the protocol and were inremission at one year (p=0.001). Tolerance was good.
Conclusion—Mesalazine suppositories 1 g threetimes a week are effective for preventing relapses of cryptogeneticproctitis. Increasing the dose to 1 g/day is effective in a highproportion of subjects who relapsed.

     

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

     

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

     

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

     

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

     

Switch from systemic steroids to budesonide in steroid dependent patients with inactive Crohn's disease

BACKGROUND: Steroid dependent patients with Crohn's disease are at high risk of developing glucocorticosteroid induced side effects. AIMS: We evaluated the possibility of switching from systemic steroids to budesonide (Entocort) in prednisolone/prednisone dependent patients with inactive Crohn's disease affecting the ileum and/or ascending colon. PATIENTS: Steroid dependent patients with a Crohn's disease activity index 200 and an increase of 60 points from baseline or withdrawal due to disease deterioration. RESULTS: After one and 13 weeks without prednisolone, relapse rates were 17% and 32%, respectively, in the budesonide group, and 41% and 65% in the placebo group (95% confidence intervals for the difference in percentages -41%, -8% and -51%, -16%; p=0.004 and p<0.001, respectively). The number of glucocorticosteroid side effects was reduced by 50% by switching from prednisolone and was similar in the budesonide and placebo groups. Basal plasma cortisol increased in both groups. CONCLUSIONS: The majority of patients with steroid dependent ileocaecal Crohn's disease may be switched to budesonide controlled ileal release capsules 6 mg without relapse, resulting in a sharp decrease in glucocorticosteroid side effects similar to placebo, and with an increase in plasma cortisol levels.     

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

     

Different microcirculatory and interstitial matrix patterns in idiopathic dilated cardiomyopathy and Chagas' disease: a three dimensional confocal microscopy study

OBJECTIVE—To analyse the morphological aspects of the extracellular matrix and microcirculation to clarify whether chronic Chagas' cardiopathy (CCC) is an accurate model to study the pathogenesis of idiopathic dilated cardiomyopathy (IDCM).
DESIGN—Thick histological myocardial sections were prepared to analyse collagen, and microcirculation was examined during confocal laser and light microscopy.
SETTING—The specimens were prepared at the pathology service of the Heart Institute of São Paulo, Brazil.
PATIENTS—Nine control hearts, eight IDCM hearts, and 10 CCC hearts were studied after necropsy.
MAIN OUTCOME MEASURES—The number of collagen struts per 100× field, the area of fibrosis (%), and the diameters of arterioles and capillaries were measured in each heart to establish outcome.
RESULTS—A smaller number (mean (SD)) of collagen struts was seen in the hearts in the IDCM group (9.1 (4.1)) than in the control (22.4 (3.2)) (p < 0.05) or CCC (15.7 (7.4)) (p > 0.05) groups. Fibrosis was greater in the CCC hearts (13.8 (10.5)%) than in the IDCM hearts (5.9 (6.6)%) (p > 0.05). Major increases in arteriole (65.4 (9.9) µm) and capillary (9.9 (1.7) µm) diameters were seen in the CCC hearts but not in the IDCM hearts (arteriole diameter 40.3 (7.9) µm; capillary diameter 7.9 (1.3) µm).
CONCLUSIONS—Hearts demonstrating CCC and IDCM present different extracellular and microvessel alterations. This suggests that distinct pathogenic mechanisms are responsible for each condition and that CCC is not an effective model to study IDCM.


Keywords: microcirculation; Chagas' disease; dilated cardiomyopathy; extracellular matrix     

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

     

Erosive oesophagitis: outcome of repeated long term maintenance treatment with low dose omeprazole 10 mg or placebo

Aims—To investigate the efficacy of dailymaintenance treatment with omeprazole 10 mg in reducing the relapserate of healed erosive oesophagitis.
Methods—Three hundred patients with erosiveoesophagitis (grade 2 or greater) received omeprazole 20 mg daily for12 weeks, followed by 40 mg daily for a further 12 weeks if required.After healing, patients were randomised to double blind treatment with omeprazole 10 mg daily or placebo for up to 18 months. On relapse thetreatment cycle was repeated.
Results—The cumulative healing rate at 12 weeksin the initial healing period was 95%, and 96% and 98% on rehealingcourses after relapse in the first and second maintenance periodsrespectively. After 12 weeks of treatment, 98% of patients were freefrom heartburn and 97% were free of all reflux related symptoms.Relapse in the subgroup of patients who relapsed in both maintenanceperiods was infrequent on omeprazole 20 mg daily: only 9% at twoyears. Gastrin concentrations rose above normal in one third ofpatients. One patient had linear hyperplasia of endocrine cells andanother had micronodular hyperplasia. There were no side effectsdefinitely attributable to omeprazole.
Conclusion—Maintenance treatment with omeprazole10 mg daily keeps about 60% of patients with erosive oesophagitis inprolonged remission. Patients relapsing once are likely to do so again; they can subsequently be treated effectively with omeprazole 20mg daily.

Keywords:erosive oesophagitis; long term maintenancetreatment; omeprazole

     

Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans

Background—During theinterdigestive state in humans, erythromycin 40 mg induces a prematureactivity front that starts in the stomach, while erythromycin 200 mginduces a prolonged period of enhanced antral contractile activity.
Aims—To study the involvement of acholinergic pathway in the motor effects of erythromycin using themuscarinic antagonist atropine and the neural 5-HT₁receptor agonist sumatriptan.
Methods—In 30 healthy volunteers,fasted antroduodenojejunal motor activity was studied by stationarymanometry. Placebo (n=10), atropine (15 µg/kg intravenous bolus plus15 µg/kg/h over 30 minutes; n=10), or sumatriptan (6 mgsubcutaneously; n=10) was administered, followed by infusion oferythromycin 40 mg or 200mg.
Results—After placebo, erythromycin40 mg induced a premature activity front with gastric onset after 19.1 (1.7) minutes in all volunteers. After atropine, erythromycin 40 mgfailed to induce a premature activity front during a 60 minute periodin all volunteers (p<0.001), while sumatriptan prevented the inductionof a premature activity front during a 60 minute period in all but onevolunteer (p<0.005). The number of antral contractions and their meanamplitude in the 60 minutes after erythromycin 200 mg did not differsignificantly after atropine or sumatriptan versus placebo.
Conclusions—The antral motoreffects of erythromycin in humans are mediated via different pathways.The induction of a premature activity front is mediated throughactivation of an intrinsic cholinergic pathway, while the induction ofenhanced antral contractile activity may be mediated via a pathwaypotentially involving activation of a muscular receptor.

Keywords:migrating motor complex; cholinergic control; antralmotility; atropine; sumatriptan

     

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

     

Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study

OBJECTIVE—To assess and compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation.
DESIGN—Prospective, randomised, single blind, placebo controlled study.
SETTING—Tertiary cardiac referral centre.
PATIENTS—186 consecutive patients (97 men, 89 women; mean (SD) age, 63 (10) years) with recurrent, symptomatic atrial fibrillation.
INTERVENTIONS—65 patients were randomised to amiodarone, 61 to sotalol, and 60 to placebo. Patients receiving amiodarone were maintained at a dose of 200 mg/day after a 30 day loading phase. The sotalol dose was 160-480 mg daily, as tolerated.
MAIN OUTCOME MEASURES—Recurrence of atrial fibrillation or side effects.
RESULTS—In the amiodarone group, 31 of the 65 patients developed atrial fibrillation after an average of six months, while 15 (11 in sinus rhythm and four in atrial fibrillation) experienced significant side effects after an average of 16 months. In the sotalol group, relapse to atrial fibrillation occurred in 47 of the 61 patients after an average of eight months; three experienced side effects during the titration phase. In the placebo group, 53 of the 60 patients developed atrial fibrillation after an average of four months (p < 0.001 for amiodarone and sotalol v placebo; p < 0.001 for amiodarone v sotalol).
CONCLUSIONS—Both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation. Amiodarone is more effective but causes more side effects.


Keywords: amiodarone; sotalol; atrial fibrillation     

Transabdominal bowel sonography for the detection of intestinal complications in Crohn's disease

Background—The course ofCrohn's disease is characterised by the occurrence of intestinalcomplications such as strictures, intra-abdominal fistulas, orabscesses. Standard diagnostic procedures may fail to show thesecomplications, in particular fistulas.
Aims—To test the value oftransabdominal bowel sonography (TABS) for the detection of intestinalcomplications in Crohn's disease.
Methods—TABS was prospectivelyperformed in 213 patients with Crohn's disease in a university basedinflammatory bowel disease referral centre. Thirty three underwentresective bowel surgery and were included in this study. The accuracyof TABS to detect strictures, intra-abdominal fistulas, or abscesseswas compared with surgical and pathological findings.
Results—TABS was able to identifystrictures in 22/22 patients and to exclude it in 10/11 patients (100%sensitivity, 91% specificity). Fistulas were correctly identified in20/23 patients and excluded in 9/10 patients (87% sensitivity, 90%specificity). Intra-abdominal abscesses were correctly detected in 9/9patients and excluded in 22/24 patients (100% sensitivity, 92% specificity).
Conclusions—In experienced handsTABS is an accurate method for the detection of intestinalcomplications in Crohn's disease. TABS is thus recommended as aprimary investigative method for evaluation of severe Crohn's disease.

Keywords:Crohn's disease complications; fistula; stricture; abscess; bowel sonography

     

Randomised comparison of the effects of nicardipine and esmolol on coronary artery wall stress: implications for the risk of plaque rupture

OBJECTIVE—To determine whether the β blocker esmolol reduces coronary artery wall stress more than the short acting dihydropyridine calcium antagonist nicardipine.
DESIGN—Randomised double blind placebo controlled trial.
SETTING—Tertiary cardiology centre.
PATIENTS—Patients with coronary artery disease.
INTERVENTIONS—20 patients were randomised double blind to an infusion of nicardipine (n = 10) or esmolol (n = 10) titrated to reduce systolic blood pressure by 20 mm Hg.
MAIN OUTCOME MEASURES—Peak systolic wall circumferential stress.
RESULTS—Esmolol reduced peak coronary stress by a mean of 0.17 × 10⁶ dyn/cm² (95% confidence interval (CI) 0.14 to 0.21 × 10⁶ dyn/cm²) compared with a reduction of 0.07 × 10⁶ dyn/cm² (95% CI 0.05 to 0.10 × 10⁶ dyn/cm²) after nicardipine. Peak systolic radius was reduced by 0.04 mm (95% CI 0.03 to 0.06 mm) after esmolol compared with an increase of 0.08 mm (95% CI 0.05 to 0.10 mm) after nicardipine. Heart rate increased by 11.5 beats/min (95% CI 6.9 to 16.2 beats/min) after nicardipine and decreased by 5.3 beats/min (95% CI 1.9 to 8.6 beats/min) after esmolol.
CONCLUSIONS—Intravenous esmolol is more effective than nicardipine at reducing circumferential coronary artery wall stress.


Keywords: β blockers; calcium channel antagonists; mechanics; coronary disease     

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

     

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

     

Expression of cell membrane complement regulatory glycoproteins along the normal and diseased human gastrointestinal tract

Background/Aims—Uncontrolled complementactivation may be of immunopathological importance in inflammatorydiseases of the gastrointestinal tract. Expression of membrane boundfactors that regulate complement activation was therefore studied in situ.
Methods—Frozen tissue specimens were obtained frompatients with Helicobacter pylori gastritis, coeliacdisease, Crohn's disease, or ulcerative colitis, and fromhistologically normal controls. Sections were examined byimmunofluorescence with monoclonal antibodies to protectin (CD59),decay accelerating factor (DAF), and membrane cofactor protein (MCP).
Results—Protectin and MCP were widely expressed innormal and diseased mucosae. MCP was generally observed basolaterallyon all epithelial cells, whereas apical protectin expression was moreintense on the epithelium of normal colonic mucosa than in the normalduodenum (p = 0.001). Epithelial DAF and to some extent protectin wereupregulated in gastritis, coeliac disease, and inflammatory boweldisease. Areas of the stomach with intestinal metaplasia expressed DAF,unlike the adjacent gastric epithelium. Parietal cells of the gastricbody expressed neither protectin nor DAF.
Conclusion—Epithelial complement inhibitorymolecules were expressed differently at various normal gastrointestinalsites and also in association with mucosal disease, suggesting variable protective potential. Such molecules could play a role in the development of gastric atrophy by protecting areas of intestinal metaplasia. Conversely, parietal cells appeared to be potentially vulnerable targets for complement attack.

Keywords:Helicobacter pylori; coeliac disease; Crohn's disease; ulcerative colitis; immunofluorescence; complementregulatory proteins