CAMPYLOBACTER PYLORI ASSOCIATED GASTRITIS IN PATIENTS WITH RHEUMATOID ARTHRITIS TAKING NONSTEROIDAL ANTI-INFLAMMATORY DRUGS

Fifty-two patients with rheumatoid arthritis taking nonsteroidalanti-inflammatory drugs were studied in order to assess thecarriage rate of Campylobacterpylori (C. pylori) with referenceto dyspeptic symptoms, endoscopic appearance and antral histology.All patients were interviewed using a standard gastrointestinalsymptom scoring questionnaire and underwent endoscopy at whichtwo antral biopsies were obtained. Sections were examined forthe presence and severity of gastritis and of C. pylori. Forty-four of 52 patients (85%) had histological evidence ofgastritis. Twenty-six of 44 (59%) patients with gastritis werepositive for C. pylori. Twenty-six of 28 patients with 'active'(polymorph infiltration) chronic gastritis were positive forC. pylori (p <0.002). Sixteen of 26 bacteria-positive patientshad gastrointestinal symptoms compared with eight of 26 bacteria-negativepatients (p < 0.05) and this may have therapeutic implications.There was no correlation between the presence of organisms andthe appearances at endoscopy. KEY WORDS: 'Active' chronic gastritis, Prevalence, Dyspepsia, Endoscopy.     

INCREASED INTESTINAL PERMEABILITY IN PATIENTS WITH RHEUMATOID ARTHRITIS: A SIDE-EFFECT OF ORAL NONSTEROIDAL ANTI-INFLAMMATORY DRUG THERAPY?

Intestinal permeability in controls and in patients with activerheumatoid arthritis was assessed by measuring the radioactivityin 24-h urine collections after oral administration of ⁵¹Cr-EDTA.Intestinal permeability in the patients was found to be significantlyincreased in comparison to controls. Of the patients, 6/7 (86%)not taking any prescribed nonsteroidal anti-inflammatory drug(NSAID) at the time of study had normal results, whereas 23/29patients (79%) taking prescribed NSAIDs displayed increasedintestinal permeability. It has not been determined beyond doubtwhether this finding is due to disease process or therapy withoral NSAIDs. KEY WORDS: Intestinal permeability, Rheumatoid arthritis, ⁵¹Cr-EDTA, Nonsteroidal anti-inflammatory drugs, Prostaglandins     

DICLOFENAC SODIUM, DIFLUNISAL AND NAPROXEN: PATIENT PREFERENCES FOR ANTI-INFLAMMATORY DRUGS IN RHEUMATOID ARTHRITIS

Ninety patients with active rheumatoid arthritis took part ina cross-over trial comparing diclofenac sodium, diflunisal andnaproxen. The efficacy of the three drugs was similar thoughthere were trends in favour of diclofenac sodium in some measurements.The incidence of side-effects was similar with the three drugsand each was chosen by a significant group of patients as continuationtherapy at the end of the study.     

LABORATORY SCALE FOR EVALUATING THE ACTIVITY OF RHEUMATOID ARTHRITIS

An evaluation was made of 24 parameters, 16 of which are generallyconsidered to relate to the activity of rheumatoid arthritis.Highly significant correlations were found between Lansbury'sactivity index and the erythrocyte sedimentation rate, serumthiol groups, blood platelets, serum iron, blood haemoglobinand the patients' own assessments of their disease. Correlationswere also found with the serum haptoglobin, serum total ironbinding capacity and the technetium index. From these parametersa continuous scale was developed for the estimation of rheumatoidactivity.     

THE EFFECT OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS ON FAECAL FLORA AND BACTERIAL ANTIBODY LEVELS IN RHEUMATOID ARTHRITIS

The faecal flora and bacterial antibody levels of 22 patientswith active rheumatoid arthritis (RA) were compared with thoseof 26 patients with osteoarthritis (OA) undergoing comparabletreatment with non-steroidal anti-inflammatory drugs (NSAIDs),and a further 22 patients with OA who were not receiving NSAIDs.Faecal counts of Clostridium perfringens were significantlyhigher in the RA patient group and in those OA patients receivingNSAIDs, compared with those OA patients not taking NSAIDs (P=0.032,P=0.0004 respectively). Total aerobic and anaerobic counts were,however, identical in all three groups. Levels of serum IgA antibody to the alpha toxin of Cl. perfringenswere higher in the RA group and in the OA group taking NSAIDsthan in OA patients not taking NSAIDs (P=0.011, P=0.055). SerumIgG antibody to alpha toxin was higher in the RA group thanin OA patients both on and off NSAIDs (P=0.019, P=0.0072) andalso a group of normal controls (P=0.032). These results suggest that the increased faecal counts of Cl.perfringens together with the associated increased antibodylevels seen in this and previous studies are more likely toresult from NSAID therapy used to treat the disease than froma disease specific changk in bowel flora. KEY WORDS: Rheumatoid arthritis, Cl. perfringens, NSAIDs     

EVENING PRIMROSE OIL IN PATIENTS WITH RHEUMATOID ARTHRITIS AND SIDE-EFFECTS OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

Forty patients with rheumatoid arthritis and upper gastrointestinallesions due to non-steroidal anti-inflammatory drugs entereda prospective 6-month double-blind placebo controlled studyof dietary supplementation with gamma-linolenic acid 540 mg/day.Nineteen patients received active therapy (as evening primroseoil 6g/day) and 21 received placebo (olive oil 6g/day). No patientstopped non-steroidal anti-inflammatory therapy but three patientsin each group reduced their dose. Other results showed a significantreduction in morning stiffness with gamma-linolenic acid at3 months and reduction in pain and articular index at 6 monthswith olive oil. Whilst gamma-linolenic acid may produce mildimprovement in rheumatoid arthritis, olive oil may itself havehitherto unrecognized benefits. KEY WORDS: Rheumatoid arthritis, Inflammation, Evening primrose oil, NSAIDs, Peptic ulcer, Gastritis     

CHRONIC NEPHROTOXICITY OF ANTI-INFLAMMATORY DRUGS USED IN THE TREATMENT OF ARTHRITIS

We determined the consumption of non-steroidal anti-inflammatorydrugs (NSAIDs) and the prevalence of chronic renal impairmentand renal papillary necrosis (RPN) in patients with varioustypes of arthritis. Ninety-four patients with chronic arthritiswho had consumed more than 1000 capsules and/or tablets of NSAIDswere studied. Renal profiles and radiological investigationssuch as intravenous urogram (IVU), ultrasonography (US) andcomputed tomography (CT) were performed to look for evidenceof RPN. Twelve patients did not complete the study. Ten of the82 patients who had completed the study (12.2%) had radiologicevidence of RPN. Five out of 53 patients (9.4%) with rheumatoidarthritis, three out of 11 patients (27.3%) with gouty arthritisand two out of seven patients (28.6%) with osteoarthritis hadRPN. Renal impairment (serum creatinine levels of 125—451µmol/I) was found in 20 patients (24.4%). The patientshad consumed 1000–26 300 capsules and/or tablets overa period ranging from 1 yr to more than 30 yr. Patients withchronic arthritis who consume excessive amount of NSAIDs areat risk of developing RPN and chronic renal impairment. KEY WORDS: Arthritis, Non-steroidal anti-inflammatory drugs, Renal papillary necrosis, Chronic renal impairment     

A GASTROSCOPIC STUDY OF THE PREDICTIVE VALUE OF RISK FACTORS FOR NON-STEROIDAL ANTI-INFLAMMATORY DRUG-ASSOCIATED ULCER DISEASE IN RHEUMATOID ARTHRITIS PATIENTS

Peptic ulcer disease (PUD) in RA patients is associated withNSAID use. This study aimed to validate the predictive valueof presumed risk factors for NSAID-associated PUD in a prospectivegastroscopic study in RA patients. Eighty-one NSAID using RApatients were prospectively divided into four presumed riskgroups according to Helicobacter pylori status and history ofPUD. As additional risk factors the following were analysed:upper gastrointestinal GI complaints; disability; daily doseof NSAID and antral gastritis. The presence of PUD in the fourrisk groups did not differ. Additionally it was found that ahistory of PUD was predictive for current PUD [odds ratio (OR)3.9; 95% CI 1.1–14]. H. pylori status was not predictive.Transformation from one ulcer type to another was rare. NSAIDdose was not a risk factor, while disability was of borderlineimportance (OR 2.1; 95% CI 1–4.8). Current upper GI complaintswere bad predictors. PUD only occurred with a concomitant antralgastritis. A history of PUD, disability and antral gastritiswere the most important predictors for current PUD. When anulcer relapsed it was of the same ulcer type as had been presentearlier. This may have practical implications for prophylaxisenabling stratification by previous ulcer type. KEY WORDS: Non-steroidal anti-inflammatory drugs, Peptic ulcer disease, H. pylori, Gastritis     

FLOCTAFENINE (IDARAC) IN THE MANAGEMENT OF RHEUMATOID ARTHRITIS

A double-blind controlled cross-over trial comparing floctafenine1.6 g daily with soluble aspirin 4.0 g daily and matching placebo,in 48 patients suffering from rheumatoid arthritis, is reported.Floctafenine and aspirin gave statistically significant reductionin morning stiffness, grip strength and better subjective assessmentthan the placebo. There was no difference in the relief of painbetween the three treatments under the conditions of this trialwhere paracetamol was allowed as an additional escape analgesic.During the period of aspirin therapy there was a higher incidenceof concurrent complaints, faecal occult blood loss and a reductionin haemoglobin. An open long-term study in 12 rheumatoid patients receivingfloctafenine 1.6 g daily for 3.6 months showed satisfactorymanagement of their clinical condition. There were no significantor serious side-effects or change in biochemical or haematologicalparameters, and patients completed their course of therapy.     

THE INFLUENCE OF CIMETIDINE ON PEPTIC ULCER IN PATIENTS WITH ARTHRITIS TAKING ANTI-INFLAMMATORY DRUGS

Patients with arthritis who take nonsteroidal anti-inflammatorydrugs (NSAIDs) often develop peptic ulceration. Withdrawal ofthe NSAID may lead to increased debility and thus it may bedesirable to continue the NSAID while attempting to heal theulceration by additional therapeutic measures. We have investigatedthe effect of cimetidine in this role. Patients with gastroscopically-provenpeptic ulcer associated with NSAID ingestion were given eithercimetidine or placebo treatment while continuing to take theirNSAIDs. It was found that the ulceration healed in some patientsover a 6-week period even on placebo treatment. There was nostatistical difference found between the healing of these ulcerswhen compared with the cimetidine-treated group. The mechanismof NSAID-induced ulceration and the reason for the above findingis discussed.     

THYMOPENTIN (TP-5) IN THE TREATMENT OF RHEUMATOID ARTHRITIS

A randomized control trial of TP-5 in rheumatoid arthritis isreported. In a multicentre study, 76 patients were treated withTP-5 50 mg or placebo three times a week for 3 weeks as a slowintravenous injection, and followed for 7 weeks. Clinical parameterssuch as the Ritchie index and sum score of swollen joints improvedsignificantly on TP-5 compared to placebo. Laboratory parametersdid not change but an increased skin test score to common recallantigens was observed. Toxicity was minimal. TP-5 is a potentiallyuseful agent in the treatment of rheumatoid arthritis, althoughfurther studies are required to determine the optimal treatmentregimen. KEY WORDS: Thymopentin, Skin tests, T-cell subsets, Joint inflammation     

MULTICENTRE STUDY OF PIROXICAM VERSUS NAPROXEN IN JUVENILE CHRONIC ARTHRITIS, WITH SPECIAL REFERENCE TO PROBLEM AREAS IN CLINICAL TRIALS OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN CHILDHOOD

Clinical trials of nonsteroidal anti-inflammatory drugs (NSAIDs)are necessary in juvenile chronic arthritis (JCA) but pose certainproblems highlighted and discussed in this study, includingrecruitment, the assessment of efficacy, and the heterogeneityof the disease. In a multicentre 8-week double-blind cross-overstudy using the double-dummy technique, piroxicam was comparedwith naproxen in 47 children with seronegative JCA aged 5–16years. No significant difference between the two treatmentswas found in either the clinical variables measured or the parent/patientand physician preference at the end of the study. Side-effectprofiles of the two drugs were similar, mainly gastrointestinaldisturbances. Piroxicam may be a useful alternative NSAID inJCA, particularly in view of its once-daily dosage. KEY WORDS: Piroxicam, Naproxen, Juvenile arthritis     

SERUM AMYLOID A PROTEIN DURING THE TREATMENT OF RHEUMATOID ARTHRITIS WITH SECOND-LINE DRUGS

Serum amyloid A protein (SAA), serum C-reactive protein (CRP)and the ESR were measured in 19 patients with rheumatoid arthritisbefore treatment and during therapy with gold, penicillamineor sulphasalazine for a mean period of 148 months (range 6—23months). All three measurements decreased significantly; however,only 7% of SAA values fell to within the normal range (18—44mg/l). compared to 38% measurements of serum CRP (>10 mg/l)and 32% of the ESR (>25 mm/h). In 8 (42%) of the 19 patients,SAA remained high (>400 mg/l) for 3 months or more whilstserum CRP was depressed below 20 mg/l; this discrepancy wasnot related to particular drugs We conclude that during treatment of rheumatoid arthritis withgold, penicillamine or sulphasalazine. SAA concentrations canbe high when serum CRP and ESR are suppressed SAA may be a moresensitive index of disease activity KEY WORDS: Rheumatoid arthritis, Serum amyloid A protein, C–reactive protein, Erythrocyte sedimentation rate     

PRELIMINARY EVIDENCE FOR GUT INVOLVEMENT IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS?

¹¹¹Indium leucocyte scans were performed on 26 patients withactive rheumatoid arthritis. An abnormal localization of radioactivitywas observed in the gut of 12 of these patients, generally inthe region of the terminal ileum, caecum and ascending colon.No difference was found in the intake of nonsteroidal anti-inflammatorydrugs between those with positive and negative scans. Two patientswith positive scans were on no medication. These observationssuggest the possibility of a primary role for a gastrointestinallesion in the aetiology of rheumatoid arthritis, although theseabnormalities could be secondary or unrelated. KEY WORDS: Gut, Rheumatoid arthritis, Indium leucocyte scan     

DICLOFENAC (VOLTAROL) IN RHEUMATOID ARTHRITIS: A REPORT OF A DOUBLE-BLIND TRIAL

A double-blind trial compared diclofenac with placebo in 44out-patients. One patient in the diclofenac group dropped outbecause of dyspepsia following psychological shock. In the placebogroup one patient dropped out because of dyspepsia and one becauseof poor therapeutic effect. Twenty of those who completed thetrial received diclofenac. The dosage was one tablet (25 mg diclofenac) t.d.s. during thefirst week. In the second (final) week, most patients had fouror six tablets. Diclofenac had a significantly greater effect on pain, grip,morning stiffness, joint tenderness and swelling, and in comparisonto previous treatments, even though the placebo group requiredsignificantly more rescue analgesic. A few patients in each group had slight dyspepsia. One in theactive and six in the placebo group complained of minor centralnervous system symptoms. There were no serious side-effects. Haematological, biochemical and urinary analyses showed no clinicallyimportant changes. It is concluded that, under the conditions described, diclofenac(Voltarol) is effective in relieving the symptoms of inflammatorypolyarthritis. It is as well tolerated as placebo medication,and had no detrimental haematological or biochemical effects.     

THE PATTERN OF RHEUMATOID ARTHRITIS IN THE INDIAN POPULATION: A PROSPECTIVE STUDY

Evaluation of polyarthritis in 110 patients in civilian andarmed force life revealed 89 with rheumatoid arthritis (RA).In the Indian population, RA seems milder and confined to thejoints. A substantial number of male patients appeared to sharefeatures with spondarthritis, often in HLA-B27 positive individuals. KEY WORDS: Prognosis, Polyarthritis, Rheumatoid factor, Tissue type, Spondarthritis.     

HLA-DR_4基因检测在类风湿关节炎诊治中的意义探讨

为了研究HLA-DR_4基因检测在类风湿关节炎诊治中的意义,对50例类风湿关节炎患者进行了HLA-DR_4的(PCR-SSP方法)检测,同时结合患者的临床表现和实验室指标进行分析。结果显示:HLA-DR_4阳性者31例(阳性率为62％);比较HLA-DR_4阳性和阴性两组患者其他指标,可见,HLA-DR_4阳性组的关节疼痛指数、ESR、类风湿因子(RF)滴度均明显高于HLA-DR_4阴性组(P值分别<0.05或0.01),手腕部X线在Ⅱ级～Ⅲ级异常变化者也以HLA-DR_4阳性组较多(P<0.005)。结果提示:HLA-DR_4基因检测是临床作为类风湿关节炎患者判断病情和估计预后有价值的指标之一,值得进一步探讨。     

A DOUBLE-BLIND CROSS-OVER EVALUATION OF KETOPROFEN (ORUDIS) AND IBUPROFEN IN THE MANAGEMENT OF RHEUMATOID ARTHRITIS

In a multi-centre double-blind cross-over trial using the double-placebotechnique, 55 patients with rheumatoid arthritis were treatedfor 10 days for each trial drug with ketoprofen (200 mg/day)and ibuprofen (1200 mg/day). Both drugs induced a clinicallyand statistically significant improvement of all the symptomsstudied, except for pain at night during ibuprofen administration.Ketoprofen displayed a therapeutic efficacy significantly superiorto ibuprofen in five out of the eight symptoms studied. Side-effects were recorded in 10 patients receiving ketoprofen(one patient withdrew because of heartburn) and in nine patientsreceiving ibuprofen.     

A STUDY OF THE ROLE OF PARVOVIRUS B19 IN RHEUMATOID ARTHRITIS

Serum and synovial tissue from 26 patients with rheumatoid arthritis(RA) (according to the diagnostic criteria of the American RheumatismAssociation) and 26 patients with osteoarthritis (OA) were examined.Among the RA group, the female to male ratio was 4.2:1, andthe age range was 44–82 yr with a mean of 64.0 yr; jointsfrom which synovium was sampled were hip (n = 12), knee (n =9), ankle (n = 3) and shoulder (n = 2). The duration of rheumatoiddisease ranged from 6 to 24 yr with a mean of 13.9 yr. Amongthe OA group, the female to male ratio was 2.25:1, and the agerange was 51–88 yr with a mean of 68.2 yr; joints fromwhich synovium was sampled were hip (n = 18) and knee (n = 8).Twenty-one patients from the RA group and 20 patients from theOA group had evidence of previous parvovirus B19 infection (serumanti-B19 IgG), and all patients from both groups were serumanti-B19 IgM negative. Synovial sections from all 52 patientswere stained with mouse monoclonal antibodies, 3H8 (to B19 capsidproteins) and