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     

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.     

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     

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS, HIATUS HERNIA, AND HELICOBACTER PYLORI, IN PATIENTS WITH OESOPHAGEAL ULCERATION

The frequency of oesophageal ulceration in 55 patients undergoingendoscopy for dyspeptic symptoms and who had recently used NSAIDswas studied, and compared with 86 patients seen in the sameclinic who had not recently used these drugs. Oesophageal ulcerationwas significantly more common in those who had used NSAIDs (P= 0.012), and also showed a highly significant association withthe presence of a hiatus hernia (P<0.001). No associationwas found between the presence of gastric Helicobacter pyloriand either oesophageal ulceration or histological oesophagitis.Patients receiving NSAIDs, especially those with a hiatus hernia,are at risk of oesophageal ulceration and presumably subsequentstricture formation. This should be borne in mind when prescribingthese agents. KEY WORDS: Anti-inflammatory drugs, Non-steroidal, Oesophagus, Oesophagitis, Oesophageal ulcer, Peptic ulcer, Stricture, Helicobacter pylori, Hiatus hernia     

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.     

ELEVATION OF SERUM ALUMINIUM CONCENTRATIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH DRUGS CONTAINING ALUMINIUM

In a group of 19 rheumatoid arthritis (RA) patients with normalrenal function, serum levels of aluminium (A1S) were monitoredduring treatment with drugs containing this metal (Al). The A1S levels during treatment were significantly higher (0.005>p>0.01)than those before treatment, i.e. 19.4 (SEM 2.3)µg/1 and12.3 (1.7), respectively. This increase in A1S was significantly(0.025>p>0.05) correlated with the pretreatment serumcreatinine level (mean value for the whole group 80.5 (SEM 4.7)mol/1) but showed no correlation with the predicted creatinineclearance. Although the increase in A1S during therapy withAl containing drugs is not dramatic in RA patients with normalrenal function, the rheumatologist should be aware of the riskof increased A1S concentration in RA patients, especially thosewith impaired renal function. KEY WORDS: Renal function, Trace metals, Arthritis, Elderly, Toxicity     

REVERSIBLE OVULATORY FAILURE ASSOCIATED WITH THE DEVELOPMENT OF LUTEINIZED UNRUPTURED FOLLICLES IN WOMEN WITH INFLAMMATORY ARTHRITIS TAKING NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

The case histories of three young women with ankylosing spondylitis,rheumatoid arthritis and a seronegative inflammatory polyarthritisundergoing investigations for infertility are presented. Ineach, non-steroidal anti-inflammatory drug (NSAID) therapy wasassociated with the recurrent development of luteinized unrupturedovarian follicles and normal ovulation following drug withdrawal.It is suggested that NSAID therapy may be an important and frequentlyoverlooked cause of anovulation and infertility. KEY WORDS: Arthritis, Non-steroidal anti-inflammatory agents, Infertility, Ovulation, Luteal phase     

COMPARISON OF FAECAL FLORAE IN PATIENTS WITH RHEUMATOID ARTHRITIS AND CONTROLS

The faecal flora of 25 out-patients with active rheumatoid arthritis(RA) was compared with that of 25 age- and sex-matched controls.A comprehensive survey revealed a significantly higher carriagerate of Clostridium perfringens in the RA population (88%) thancontrols (48%) (p<0.01). Coliform counts also tended to behigher, but there were no other significant differences betweenpatients and controls. When the study was enlarged to include a further 113 RA patientswith variable disease activity and a further 38 controls, clostridiawere again more frequently carried by those with RA (70%) thancontrols (45%) (p<0.01) and clostridial counts were significantlyhigher in the patient group (p = 0.006). Moreover, counts inpatients with active or moderately active disease were significantlyhigher than in those with inactive disease (p < 0.001). These data are consistent with the hypothesis that Cl. perfringensplays a role in triggering or is otherwise associated with diseaseactivity in RA. The findings may be alternatively an effectof the disease or its treatment with, for example, anti-inflammatorydrugs. KEY WORDS: Rheumatoid arthritis, Faecal flora, Closiridium perfringens ^*Present address: Department of Bactenology, University MedicalSchool, Edinburgh, UK. Present address: Central P.H.L., Division of Hospital Infection,61 Colindale Avenue, London NW9 5HT, UK.     

KNEE LAXITY IN PATIENTS WITH OSTEOARTHRTTIS AND RHEUMATOID ARTHRITIS

Thirty-four patients with osteoarthritis (OA) and 32 patientswith rheumatoid arthritis (RA) were studied to determine theeffects of OA and RA on the laxity of the knee joints. Laxitywas measured with the Genucom Knee Analysis System. The antero-posteriorlaxity of the OA and RA knees was greater than the control,normal knees in the early stage, and decreased with the severityof disease in OA, but not in RA. Severe OA and RA were associatedwith a restricted internal-external rotation at the knee jointcompared with the control. Internal-external rotation decreasedwith worsening of both diseases. Varus-valgus laxity tendedto increase slightly with the severity of disease. While themorphological changes of the cruciate ligaments in advancedOA and RA were not statistically different, the laxity of OA-afflictedknees was affected slightly by the severity of the damage tothe cruciate ligaments. KEY WORDS: Osteoarthritis, Rheumatoid arthritis, Knee joint, Laxity, Cruciate ligament     

BIOAVAILABILITY OF HYDROXYCHLOROQUINE TABLETS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Nine patients with RA received two doses of 155 mg racemic hydroxychloroquineeach, as a tablet and by i.v. infusion, in a randomized cross-overdesign study. Blood concentrations over the first 32 h followingeach dose were determined. Bioavailability was estimated usinga sequential exponential least squares deconvolution method. The mean fraction absorbed from the tablet was 0.79 (range 0.39to 1.27). The mean absorption lag-time was 1.3 h (range 0.5to 3.7 h) and the mean time for 50% absorption was 4.3 h (range1.9 to 10.3 h). Mean rate and extent of hydroxychloroquine absorptionwere not significantly different from that previously reportedfor healthy volunteers, although the interindividual variabilityin absorption parameters was greater in the patient group. Variabilityin the extent of absorption would lead to differences in steady-statehydroxychloroquine concentrations between patients, potentiallycontributing to the variability in response observed in clinicalpractice. KEY WORDS: Pharmacokinetics, Hydroxychloroquine, Bioavailability Present address: Department of Pharmacy, University of Manchester,Manchester M13 9L     

PREVALENCE OF SELF-REPORTED DEPRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS

The prevalence of self-reported depressive symptoms was investigatedin a case-control study of patients with rheumatoid arthritis(RA) attending an out-patient clinic at the Middlesex Hospital.Patients selected their own controls, matched for age and sex.Previous attempts to measure depressive symptoms in RA havesuffered from measurement error due to criterion contamination,where psychological symptoms augment depressive scores. A totalof 163 patients (77% of the sample) and 115 matched pairs completedthe Hospital Anxiety and Depression Scale (HADS). The resultsIndicated that RA patients are more depressed and anxious thancontrols. The prevalence of depression above the cut-point was15%. This figure is comparable to other reports adjusted forcriterion contamination, but is lower than that of other studieswhich employ ‘contaminated’ tools. The depressionscale of the HADS appeared to be relatively free of criterioncontamination. Subject to further reliability testing, the HADSmay be a practical screening tool for practitioners to assesspatients in need of psychological interventions. KEY WORDS: Depression, Rheumatoid arthritis, Criterion contamination     

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.     

DENTAL STUDY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Twenty-one patients with rheumatoid arthritis took part in acomparison of three toothbrushes, each used for one month ina randomized trial. The three toothbrushes were a conventionaltoothbrush with modified handle to allow ease of gripping, anelectric toothbrush, and thirdly a fingerstall attached to anormal toothbrush. There was no change in the patients' rheumatoid status duringthe trial. The patients were scored for plaque and gingivalchanges but no difference was found between the three toothbrushes. We recommend a standard toothbrush with a modified grip forthe rheumatoid hand; the extra expense of an electric toothbrushcannot be justified. ^*Paper read at the Annual Meeting of the British Associationfor Rheumatology and Rehabilitation, London, 17 April, 1980.     

LACK OF INTERACTION BETWEEN SULPHASALAZINE AND CIMETIDINE IN PATIENTS WITH RHEUMATOID ARTHRITIS

The interaction between sulphasalazine and cimetidine has beenstudied, a drug combination which is quite likely in view ofthe higher incidence of peptic ulceration in patients with RA.Nine patients with RA on sulphasalazine (group I) were givencimetidine 400 mg three times daily and followed up for 18 weeks.In addition, five patients on sulphasalazine alone (group II),who served as a control group, were also followed up in thesame manner as group I. Monitoring included assessment of diseaseactivity and haematological variables, and measurement of plasmaand urinary levels of sulphapyridine and its metabolites. Therewas no significant change in either the haematological parametersor sulphapyridine pharmacokinetics upon administration of cimetidine.We therefore conclude that cimetidine may be safely used inpatients with RA who are being treated with sulphasalazine. KEY WORDS: Sulphasalazine, Cimetidine, Interaction ^*Present address: Pharmaceutical Sciences Institute. Universityof Aston. Aston Triangle. Birmingham B4 7EY.     

THE USE OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IN PAEDIATRIC RHEUMATIC DISEASES

The use of NSAIDs for arthritis differs in children from adultsin their indications, uses and pharmacokinetics, and fewer areavailable. Children with arthritis are assessed differently,as they complain less of pain. Salicylates, indomethacin andibuprofen are used for the fever of systemic JCA. For controlof joint symptoms, diclofenac, ibuprofen, tolmetin and naproxenare equal in their efficacy and tolerance: salicylates and indomethacinare no more effective but more toxic. Children tolerate NSAIDswell. Gastrointestinal symptoms appear to be less common thanin adults, but the evidence regarding endoscopic changes isconflicting. Renal toxicity is rare. Tolmetin can cause pseudoproteinuriaand naproxen pseudoporphyria. The liver in systemic JCA is vulnerableto drug toxicity. A therapeutic trial of an NSAID should continuefor 8 weeks. Interactions with methotrexate and carbonic anhydraseinhibitors for glaucoma complicating iridocyclitis may occur. KEY WORDS: Children, JCA, Juvenile rheumatoid arthritis, Drug therapy, Side effects     

METABOLIC ABNORMALITIES OF TRYPTOPHAN AND NICOTINIC ACID IN PATIENTS WITH RHEUMATOID ARTHRITIS

The mean plasma total tryptophan concentration of 13 long-standingrheumatoid arthritis patients was found to be lower than thatof seven nonrheumatoid control subjects, but the plasma nicotinicacid concentration was unchanged. In the rheumatoid patientsthe urinary excretion of the tryptophan metabolites, kynurenine,xanthurenic acid and 3-hydroxyanthranilic acid, was increasedseveral fold, but the excretion of N-methylnicotinamide wasnormal. These findings are discussed in relationship to thedietary intakes of tryptophan, nicotinic acid and pyridoxine,the effect of antirheumatoid drugs on plasma tryptophan andliver tryptophan pyrrolase, and the requirement of rheumatoidpatients for pyridoxine. ^*Present address: The National Research Institute for NutritionalDiseases, P.O. Box 70, Tygerberg 7505, South Africa.     

早期类风湿关节炎病人中类风湿因子的临床意义

报告９６例早期类风湿关节炎病人血清中ＩｇＭ类风湿因子和ＩｇＡ免疫球蛋白测定的３年随访结果。根据Ｘ线摄片评价骨侵蚀的情况。结果发现，ＩｇＭ类风湿因子和ＩｇＡ免疫球蛋白越高，越容易引起发病头３年内的骨侵蚀。这说明它们是早期诊治类风湿关节炎的２项有价值的实验室指标。这个结果还为早期使用ＩＩ线药物提供了科学依据。     

FEMORAL BONE MASS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND OSTEOARTHROSIS

Femoral bone mass has been measured in 42 patients with rheumatoidarthritis and in 27 with osteoarthrosis. Measurements were madeby scanning the leg with a photon beam from ²⁴¹Am. The resultshave been compared with normal subjects and correlated withclinical, biochemical and radiological parameters of the arthriticpatients. In general, femoral bone mass was lower than normalin patients with arthritic changes. Reduced physical activityrather than the arthritis itself seemed to be the cause of thelow bone mass. In rheumatoid arthritis the bone mass appearedto be an accurate representation of the clinical assessmentof the disease.