Five genetic markers in the interleukin 1 family in relation to inflammatory bowel disease

Background—An imbalance between theproinflammatory cytokine interleukin 1β (IL-1β) and theanti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) has beenpostulated as a pathogenic factor in inflammatory bowel disease (IBD).
Aims—To study allelic frequenciesof novel polymorphisms in the genes for IL-1β and IL-1ra in patientswith IBD and to assess the relation between ex vivo cytokine productionand allelic variants of the IL-1β and IL-1ra genes.
Subjects—Two hundred and seventyhealthy controls, 74 patients with ulcerative colitis (UC), 72 withCrohn's disease (CD), 40 with primary sclerosing cholangitis for theallelic frequencies, and 60 healthy individuals for the ex vivostimulation test.
Methods—Genotyping was performed bypolymerase chain reaction and subsequent cleavage with specificendonucleases (Mwo1, MspAI1, Alu1, Taq1, BsoF1) for five novelrestriction fragment length polymorphisms (RFLPs) in the genes forIL-1ra and IL-1β.
Results—No significant differences were found inthe allelic frequencies or allele carriage rates of the markers in theIL-1β and IL-1ra genes between CD, UC, and healthy controls. Noassociation between the genetic markers and cytokine production levelswas observed. Patients with UC carried the combination of both the infrequent allele of the Taq1 RFLP and the Mwo1 RFLP significantly morefrequently (35.2% in UC versus 71.1% in controls).
Conclusions—UC is associatedwith carriage of both infrequent alleles of the Taq1 and Mwo1 RFLPs.However, it could not be confirmed whether the association reflects apathogenic mechanism underlying UC.

     

Mast cell mediated ion transport in intestine from patients with and without inflammatory bowel disease

Background—Mast cells have been shown to regulateintestinal ion transport in animal models and normal human colon buttheir physiological role in human intestinal inflammatory disorders is unknown.
Aims—To examine mast cell regulation of iontransport in inflammatory bowel disease (IBD).
Subjects and methods—Small and large intestinewas obtained from patients with and without IBD undergoing surgicalresection. Short circuit current (Isc) responses to rabbitantihuman IgE, histamine, and electrical stimulation were measured inUssing chambers. Specimens were also examined for mast cell numbers and degree of inflammation.
Results—Isc responses to anti-IgEand histamine were smaller in magnitude in IBD compared with non-IBDtissues. In all tissues, anti-IgE Isc responses werereduced by about 80% in chloride free buffer. The histamineH₁ receptor antagonist, pyrilamine, decreased anti-IgEresponses in non-IBD tissues. Greater inhibition with pyrilamine wasseen in IBD small intestine but its effect was less in IBD colon.Histamine pretreatment of non-IBD control tissues reduced anti-IgEresponses to levels seen in IBD colon but had no effect in smallintestine. Mast cell numbers were greater in IBD compared with non-IBDsmall intestine while no differences were observed between the colonicgroups. Isc responses to anti-IgE were not correlated withthe degree of mucosal inflammation.
Conclusions—This study provides further evidencethat mast cells are capable of mediating alterations of ion transportin human gut but that this regulatory role may be altered in IBD. Thedata suggest that prior activation of mast cells with release ofhistamine may account for the reduced secretory response to anti-IgEobserved in IBD colonic tissues.

Keywords:mast cells; intestine; ion transport; histamine; ulcerative colitis; Crohn's 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

     

General and cancer specific mortality of a population based cohort of patients with inflammatory bowel disease: the Florence study

Background—A population basedepidemiological study identified all the patients diagnosed withulcerative colitis (UC) or Crohn's disease (CD) resident in theFlorence area in the period 1978-1992.
Aims—To assess the mortality of unselectedpatients with inflammatory bowel disease (IBD) in a Mediterranean country.
Methods—Overall, 920 patients (689 UC and 231 CD)were followed until death or end of follow up (31 December 1996).Information on vital status was available for all except eight patients(0.9%); 70 deaths were identified (23 in patients with CD and 47 inpatients with UC). Expected deaths were estimated on the basis of five year age group, gender, and calendar year national mortality rates. Standardised mortality ratios (SMR) and 95% confidence intervals were calculated.
Results—General mortality was significantly lowerthan expected in UC (SMR 0.6; 95% confidence interval 0.4 to 0.8), dueto a reduced number of cardiovascular and, possibly, smoking related deaths. Cancers of the respiratory tract were significantly reduced inUC but tended to be increased in patients with CD. These latter patients had not only an increased cancer mortality but also a 40%increased risk of dying for all causes already evident in the firstfive year follow up period and persisting thereafter. In contrast, inpatients with UC, SMRs were initially very low but tended to increasesteadily over the follow up period. Gastrointestinal deaths wereparticularly increased in patients with CD, but only moderately inthose with UC. Overall, there was some evidence of a twofold increasedmortality for colorectal cancer, the risk being highest for rectalcancers in patients with UC. A non-significant excess of deaths due tohaemolymphopoietic malignancies and suicides was also observed.
Conclusions—This study, the first in aMediterranean country, supports the existence of two divergentmortality patterns for patients with UC and CD, possibly explained bydifferences in smoking habits and by a greater severity of CD.

     

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

     

A UK training programme for nurse practitioner flexible sigmoidoscopy and a prospective evaluation of the practice of the first UK trained nurse flexible sigmoidoscopist

Background—Colonoscopic surveillance is astandard procedure in many patients with long standing, extensiveulcerative colitis (UC), in order to avoid death from colorectalcancer. No conclusive proof of its benefits has been presented however.
Aims—To evaluate the association betweencolonoscopic surveillance and colorectal cancer mortality in patientswith UC.
Patients—A population based, nested case controlstudy comprising 142 patients with a definite UC diagnosis, derivedfrom a study population of 4664 patients with UC, was conducted.
Methods—Colonoscopic surveillance in all patientswith UC who had died from colorectal cancer after 1975 was comparedwith that in controls matched for age, sex, extent, and duration of thedisease. Information on colonoscopic surveillance was obtained from themedical records.
Results—Two of 40 patients with UC and 18 of 102 controls had undergone at least one surveillance colonoscopy (relativerisk (RR) 0.29, 95% confidence interval 0.06 to 1.31). Twelve controls but only one patient with UC had undergone two or more surveillance colonoscopies (RR 0.22, 95% confidence interval 0.03 to 1.74), indicating a protective dose response relation.
Conclusion—Colonoscopic surveillance may beassociated with a decreased risk of death from colorectal cancer inpatients with long standing UC.

Keywords:colonoscopic surveillance; colorectal cancer; ulcerative colitis; epidemiology

     

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

     

Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin 10 during intestinal inflammation

Background—Concentrations of pro-inflammatorycytokines are increased in the intestinal mucosa of patients withactive inflammatory bowel disease (IBD). Polymorphonuclear neutrophilgranulocytes (PMN) are the most abundant cell type in intestinallesions in IBD. Interleukin 10 (IL-10) is an importantcontra-inflammatory cytokine which induces downregulation ofpro-inflammatory cytokines.
Aims—To investigate whether PMN from patients withIBD or infectious colitis, respectively, secrete increased amounts ofpro-inflammatory cytokines and can be regulated by IL-10.
Methods—Secretion (ELISA) as well as correspondingmRNA levels (semiquantitative RT-PCR) of pro-inflammatory cytokines(IL-1β, TNF-α) and of IL-1 receptor antagonist were assessed inperipheral PMN.
Results—PMN from patients with IBD are primed tosecrete enhanced amounts of pro-inflammatory cytokines accompanied bydetection of corresponding mRNAs in comparison with normal controls.This finding is not specific for IBD but rather reflects intestinal inflammation in general. IL-10 markedly inhibited pro-inflammatory cytokine secretion as well as corresponding mRNA concentrations.
Conclusions—PMN are an important source ofpro-inflammatory cytokines in patients with intestinal inflammation andcan be downregulated by IL-10.

Keywords:granulocytes; interleukin 1β; interleukin 10; inflammatory bowel disease; intestinal immunity; inflammation; neutrophils; tumour necrosis factor α

     

Increased state of activation of CD4 positive T cells and elevated interferon γ production in pouchitis

Background—Immunoregulatory abnormalities of Tcells might be of importance in the pathogenesis of pouchitis afterileoanal pouch anastomosis (IAP).
Aims—To characterise T cell subsets, their stateof activation, and production of cytokines in inflamed and non-inflamedpouches in patients with ulcerative colitis (UC) and familialadenomatous polyposis (FAP). The influence of T cell activation onmucosal transformation was also studied.
Patients—Mucosal biopsy specimens were taken from42 patients with IAP (33 with UC and nine with FAP).
Methods—Mononuclear cells were isolated bystandard techniques and characterised by three colour flow cytometry.Interferon γ (IFN-γ) production was studied using the ELISPOT technique.
Results—In patients with UC with pouchitis therewas a significant increase in the CD4:CD8 ratio, expression ofactivation markers on CD3+ cells, and number of IFNγ producingmononuclear cells compared with patients with UC without pouchitis(CD4:CD8 ratio 1.3 (range 0.7-2.7) versus 0.6 (0.1-1.0), p=0.012). Inaddition, a positive correlation between increased crypt depth and thenumber of CD4+ cells (r=0.57) was shown.
Conclusion—The observed increase in activatedmucosal CD4+ T cells and IFN-γ production might lead to mucosaldestruction and crypt hyperplasia as seen in pouchitis.

Keywords:pouchitis; T cell activation; mucosaltransformation

     

Effects of smoking on the urine excretion of oral 51Cr EDTA in ulcerative colitis

Background—Smokers have a reduced risk andex-smokers an increased risk of ulcerative colitis (UC). Stoppingsmoking often precedes onset and relapses. Smoking reduces the 24 hoururine excretion of oral chromium-51 labelled EDTA in healthy individuals.
Aims—To estimate the effects of smoking on theurine excretion of oral ⁵¹Cr EDTA in well characterisedpatients with UC.
Subjects—Sixteen smoking and 16 non-smokingpatients with UC in remission were studied. The non-smokers had neversmoked. Most were taking 5-aminosalicylic acid. No patient tooksteroids or immunosuppressants. The control group comprised 25 smoking healthy volunteers and 25 who had never smoked. The median cigarette consumption was equal in the patients and volunteers.
Methods—The 24 hour urine excretion of oral⁵¹Cr EDTA was measured and the results were correlated withsmoking habits, number of cigarettes, and disease extent.
Results—Patients with UC had significantly higher24 hour urine recoveries than healthy controls (p=0.04). Thisdifference was more pronounced when patients who smoked were comparedwith healthy smokers (p=0.005) No significant differences were found when comparing non-smoking patients with non-smoking controls or whencomparing smoking and non-smoking patients. Urine recoveries did notcorrelate with number of cigarettes or disease extent. Smoking was moreprevalent in patients with a more limited disease extent (p=0.033).
Conclusions—Effects of smoking on the urineexcretion of ⁵¹Cr EDTA in health were abolished by thepresence of UC. The protective effects of smoking in established UC arenot due to a moderating effect of smoking on intestinal permeability.

Keywords:ulcerative colitis; smoking; intestinalpermeability; ⁵¹Cr EDTA

     

Relation between Heberden's nodes and distal interphalangeal joint osteophytes and their role as markers of generalised disease

OBJECTIVE—Heberden's nodes are often used as a marker for osteoarthritis (OA). This study examined how often Heberden's nodes and radiological distal interphalangeal (DIP) osteophytes coexist in the same digit and the sensitivity, specificity, and positive predicative value of each for OA at different sites or generalised disease.
METHODS—This was a population-based study of 660 middle aged women taking part in a twin study of OA. Distal interphalangeal osteophytes were defined radiologically and graded on a four point scale (0-3) using a published atlas of individual features. Heberden's nodes were defined by standardised clinical examination. OA in other joints (knees, proximal interphalangeal (PIP) joints and carpometacarpal (CMC) joints) was defined radiologically using a published atlas.
RESULTS—Poor agreement was observed between a Heberden's node (HN) and a radiological distal interphalangeal osteophyte in the same finger of the same hand (κ statistic (95% CI) = 0.36 (0.33, 0.39)). Although HN and radiological DIP osteophytes had similar sensitivity, the specificity and positive predicative value of DIP osteophytes was considerably higher for detecting knee, CMC, PIP OA, and OA in more than two groups of joints (knee, CMC, and DIP joints).
CONCLUSION—HN are not synonymous with DIP osteophytes. Radiological DIP osteophytes are a better marker of knee and multiple joint OA than HN. HN may still be an imperfect surrogate for hand OA when radiology is impractical, but are not an accurate marker of generalised disease.

Keywords: Heberden's nodes; osteoarthritis; distal interphalangeal joint osteophytes     

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

     

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     

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

     

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

     

Hepatitis G virus infection in primary Sjögren's syndrome: analysis in a series of 100 patients

OBJECTIVE—To determine the prevalence and clinical significance of hepatitis G virus (HGV) infection in a large cohort of patients with primary Sjögren's syndrome (SS).
PATIENTS AND METHODS—The study included 100 consecutive patients (92 female and eight male), with a mean age of 62 years (range 31-80) that were prospectively visited in our unit. All patients fulfilled the European Community criteria for SS and underwent a complete history, physical examination, as well as biochemical and immunological evaluation for liver disease. Two hundred volunteer blood donors were also studied. The presence of HGV-RNA was investigated in the serum of all patients and donors. Aditionally, HBsAg and antibodies to hepatitis C virus were determined.
RESULTS—Four patients (4%) and six volunteer blood donors (3%) presented HGV-RNA sequences in serum. HGV infection was associated with biochemical signs of liver involvement in two (50%) patients. When compared with primary SS patients without HGV infection, no significant differences were found in terms of clinical or immunological features. HCV coinfection occurs in one (25%) of the four patients with HGV infection.
CONCLUSION—The prevalence of HGV infection in patients with primary SS is low in the geographical area of the study and HCV coinfection is very uncommon. HGV infection alone does not seen to be an important cause of chronic liver injury in the patients with primary SS in this area.

Keywords: Sjögren's syndrome; sicca syndrome; hepatitis G virus; hepatitis C virus; hepatitis B virus     

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

     

Serum interleukin 12 concentration in juvenile chronic arthritis

OBJECTIVES—The aim of this study was to evaluate serum interleukin (IL) 12 concentration in patients with juvenile chronic arthritis (JCA), according to disease subtype, activity, and duration. IL12 has been demonstrated to prime the selective expansion of T helper (Th) cells with a Th1-type pattern of cytokine production.
METHODS—Sixty eight serum samples from 50 JCA patients (12 systemic, 12 polyarticular, 26 pauciarticular), 20 serum samples from age matched healthy controls were tested with two different immunoassays specific for total IL12 (p40 and p70 heterodimer) and for IL12 (p70) heterodimer, respectively. The following disease activity parameters were evaluated: (a) presence of arthritis at least in one joint, (b) physician global estimate of disease activity, (c) disability index according to the Childhood Health Assessment Questionnaire (CHAQ), (d) C reactive protein (CRP).
RESULTS—Total IL12 (p40 and p70 heterodimer) was significantly higher in JCA active patients than in those on clinical remission and in healthy controls (p < 0.001). Conversely, detectable concentrations of IL12 (p70) heterodimer were found in three active JCA patients only. Moreover, total IL12 (p40 and p70 heterodimer) showed a significant negative correlation both with time from disease diagnosis (r = −0.29, p = 0.04) and, for the pauciarticular subgroup, with disease activity duration (r = − 0.71, p < 0.001).
CONCLUSIONS—This study shows that the p40 moiety of IL12 is increased in serum samples from active JCA patients, especially in the earliest phases of the disease, whereas biological active IL12 (p70) heterodimer is virtually undetectable.

Keywords: juvenile chronic arthritis; interluekin 12; cytokines; T helper cells     

Eradication of Barrett's mucosa with argon plasma coagulation and acid suppression: immediate and mid term results

Background—Intestinal metaplastic mucosa inBarrett's oesophagus can be replaced by squamous epithelium aftermucosal thermal ablation associated with acid suppression therapy.
Aims—To assess whether restoration of squamousepithelium can be obtained after ablation of Barrett's oesophagususing argon plasma coagulation (APC) associated with proton pumpinhibitor (PPI) therapy.
Methods—Thirty one patients with Barrett'soesophagus received APC. Omeprazole (40 mg/day) was given from thefirst APC application to one month after completion of the treatment,then given symptomatically. Twenty four hour pH-metry was performedduring endotherapy.
Results—Complete re-epithelialisation wasvisualised at endoscopy in 25/31 patients (81%) after a mean number of2.4 APC sessions (range 1-4). Only partial squamousre-epithelialisation was observed in three patients and three othershad no eradication. At histological assessment, eradication ofBarrett's oesophagus was only confirmed in 19/31 patients (61%) dueto the presence of a few residual Barrett's glands under the newsquamous epithelium. Complete eradication was related to a Barrett'soesophagus segment length of less than 4 cm and the absence ofcircumferential extension but not to the normalisation of oesophagealacid exposure under PPI therapy. Seventeen patients with apparentlycomplete endoscopic and histological eradication of Barrett'soesophagus were re-evaluated at one year; eight (47%) disclosedrelapsing islands of Barrett metaplasia despite continuous omeprazoletherapy (10-40 mg/day).
Conclusions—APC combined with 40 mg omeprazoledaily can eradicate Barrett's mucosa with apparent squamousre-epithelialisation in the majority of patients even in the absence ofnormalisation of oesophageal acid exposure. However, one year afterendotherapy for Barrett's oesophagus, relapse is frequent but limitedin extent.

Keywords:Barrett's oesophagus; argon plasma coagulation; omeprazole; gastro-oesophageal reflux; Barrett's adenocarcinoma

     

Intestinal metaplasia at the squamocolumnar junction in patients attending for diagnostic gastroscopy

Background—The incidence of adenocarcinoma of theoesophagus and gastric cardia is increasing rapidly. Barrett'soesophagus is the major risk factor. Intestinal metaplasia at thesquamocolumnar junction in the absence of Barrett's oesophagus iscommon but its relation to adenocarcinoma and gastro-oesophageal refluxdisease is unclear.
Aims—To study the prevalence and clinical,endoscopic, and histological associations of intestinal metaplasia atthe squamocolumnar junction.
Methods—Biopsy specimens were taken from 120 randomly selected patients undergoing routine diagnostic endoscopy.Eight biopsy specimens, taken from above and below the squamocolumnarjunction, gastric fundus, and gastric antrum, were stained withhaematoxylin/eosin, alcian blue/periodic acid-Schiff, and Gimenez, andgraded independently by one pathologist.
Results—Intestinal metaplasia at thesquamocolumnar junction was found in 21 patients (18%). Metaplasia wasassociated with increasing age (p<0.01) and antral intestinalmetaplasia (p=0.04). Logistic regression analysis revealed that age wasthe only independent predictor (p<0.01). There was no association withsymptomatic, endoscopic, or histological markers of gastro-oesophagealreflux disease.
Conclusions—Intestinal metaplasia at thesquamocolumnar junction is a common finding. It is associated withincreasing age but not gastro-oesophageal reflux disease.

Keywords:intestinal metaplasia; Barrett's oesophagus; gastro-oesophageal reflux disease; oesophagus; gastric cardia; adenocarcinoma