SLE发病中可溶性细胞间粘附分子-1变化的研究

目的：研究呆溶性细胞间粘附分子－１在系统性红斑狼疮中的变化。方法：用双抗体夹心ＥＬＩＳＡ方法对２５例活动期ＳＬＥ病人血清和末梢血单个核细胞培养上清液ｓＩＣＡＭ－１水平进行检测。对部分稳定期病人重复检测。结果：活动期ＳＬＥ病人血清ｓＩＣＡＭ－１水平较正常对照组明显增高，活动期ＳＬＥ病人ＰＢＭＣ培养上清液中ｓＩＣＡＭ－１水平低于正常对照组，但两组间无明显差异。     

THE EVOLUTION OF A CASE OF OVERLAP SYNDROME WITH SYSTEMIC SCLEROSIS, RHEUMATOID ARTHRITIS AND SYSTEMIC LUPUS ERYTHEMATOSUS

An unusual case of overlap syndrome which evolved over a 12-yearperiod is described. The patient initially presented with limitedcutaneous systemic sclerosis. She then developed seropositiveerosive rheumatoid arthritis and subsequently vasculitis withpositive lupus serology. There was no evidence that she hadmixed or undifferentiated connective tissue disease, and antibodyto ribonuclearprotein was negative. This unusual combinationof connective tissue disorders in one patient is reported andthe literature is reviewed. KEY WORDS: Overlap syndrome, Scleroderma, Rheumatoid arthritis, Systemic lupus erythematosus     

LEVELS OF CIRCULATING INTERCELLULAR ADHESION MOLECULE-1 AND -3 BUT NOT CIRCULATING ENDOTHELIAL LEUCOCYTE ADHESION MOLECULE ARE INCREASED IN PATIENTS WITH RHEUMATOID VASCULITIS

The aim of this study was to investigate whether levels of circulatingadhesion molecules reflect vascular inflammationin rheumatoidvasculitis (RV). Levels of circulating intercellular adhesionmolecule-1 (cICAM-1), c-ICAM-3 and circulating endothelial leucocyteadhesion molecule (cE-selectin) were determined in 14 patientswith RV and compared to 47 patients with rheumatoid arthritis(RA) and 100 healthy donors (HD). Enzyme-linked immunosorbentassays were used to quantify cICAM-1, cICAM-3 and cE-selectin.We found that in RV significantly (P<0.0001) elevated levelsof cICAM-1 and cICAM3, butnot cE-selectin, were found when comparedwith RA patients. Levels > 2 S.D. above the mean level ofHD were present for cICAM-1, cICAM-3 and cE-selectin in 57,71 and 21%, respectively of patients with RV and 2, 21 and 44%,respectively of the RA patients. Increased levels of both cICAM-1and cICAM-3 were found in 43% of the RV patients and in noneof the RA patients. Comparison of the serum levels of patientsstudied in an active and inactive phase of RV revealed significantlylower levels of cICAM-3 levels in the inactive phase. In conclusionwe find that determination of cICAM-1 and cICAM-3 may be usefulas a marker of vascular inflammation in patients with RV. KEY WORDS: Adhesion molecules, Rheumatoid arthritis, Vasculitis, cICAM-1, cICAM-3, cE-selectin     

DIGITAL VASCULITIS ASSOCIATED WITH JOINT SEPSIS IN RHEUMATOID ARTHRITIS

Digital vasculitis complicating RA is not infrequent and isusually benign but may herald the onset of systemic vasculitis.A case is reported of a man with longstanding seropositive RAwho developed digital vasculitis in association with septicaemiaand multiple joint sepsis. Awareness that the onset of digitalvasculitis in RA may be related to infection is important. Thisis especially so since aggressive immunosuppressive therapyis often used in patients with systemic vasculitis. KEY WORDS: Rheumatoid arthritis, Vasculitis, Septic arthritis     

PLASMA LEVELS OF INTERLEUKIN-1-ALPHA IN RHEUMATOID ARTHRITIS

Interleukin-1-beta (IL-1ß has been implicated as aninflammatory mediator in rheumatoid arthritis (RA) but littleis known about the related cytokine, IL-1, in this disease.IL-1 has biological properties similar to IL-1ß but,unlike IL-1ß remains mostly cell-associated. In thisstudy plasma IL- was measured by radioimmunoassay in patientswith RA and in healthy controls. Plasma levels were comparedwith conventional measures of disease activity. The mean levelsin the two groups were not significantly different and, withinthe patient group (n = 53), the only significant cross-sectionalcorrelation was between plasma IL-1 and ESR. In longitudinalstudies, some individual patients had plasma IL-1 levels thatcorrelated with different measures of disease activity. We concludethat while IL- may be involved in the immunopathogenesis ofRA, its measurement in plasma seems to offer little of clinicalvalue. KEY WORDS: Interleukin-1-alpha, Plasma, Rheumatoid arthritis, Prospective longitudinal study     

PLASMA LACTOFERRIN AND NEUTROPHIL ELASTASE IN RHEUMATOID ARTHRITIS AND SYSTEMIC LUPUS ERYTHEMATOSUS

In order to assess lactoferrin (LF), stored in specific granulesof neutrophils, as a marker of inflammation, LF was measuredin plasma and serum samples of patients with active rheumatoidarthritis (RA) and systemic lupus erythematosus (SLE). In activeRA, the median plasma LF level (800 ng/ml) was significantlyhigher than in normal individuals (220 ng/ml) (P <0.000 01)and patients with active SLE (235 ng/ml) (P <0.000 01). Medianplasma elastase-proteinase inhibitor complex (EPIC) and C-reactiveprotein (CRP) levels were also significantly higher in patientswith RA than in normal individuals (P <0.000 01) and activeSLE (P <0.000 01 for both EPIC and CRP). Elevations of LF,EPIC and CRP in RA were independent of rheumatoid factor titres.Plasma lactoferrin in RA correlated significantly with EPIC(Rs = 0.7, P <0.0001), CRP (Rs = 0.72, P <0.0001) andabsolute neutrophil counts (Rs = 0.483, P <0.02), but surprisinglynot with the Ritchie index, with which CRP showed a weak butsignificant correlation (Rs = 0.27, P<0.05>0.025). Thusplasma LF and EPIC are markers of inflammation in RA and theirlevels may reflect release of mediators of inflammation intothe joint space and periarticular tissue. KEY WORDS: Inflammation, Elastase-proteinase inhibitor complex, C-reactive protein, Disease activity     

INCREASED APOTRANSCOBALAMIN II LEVELS IN RHEUMATOID ARTHRITIS

The distribution of endogenous cobalamin among serum cobalamin-bindingproteins was studied in 30 patients with active rheumatoid arthritis(RA) and 27 in clinical remission The mean total serum cobalamin concentration (holo-transcobalaminI and II) was similar in both groups of patients, whereas meanapotranscobalamin II was significantly increased in patientswith active RA. The clinical significance of this finding isnot yet established but it might be a useful parameter for theevaluation of disease activity in RA KEY WORDS: Rheumatoid arthritis, Serum cobalamin-binding proteins, Apotranscobalamin II, Vitamin B₁₂ binding proteins     

系统性红斑狼疮患者淋巴细胞粘附分子表达的观察

用流式细胞术及免疫双荧光染色法，分析了３５例系统性红斑狼疮（ＳＬＥ）患者外周血淋巴细胞粘附分子表型（ＣＤ＿（１１ａ）／ＬＦＡ－ｌα、ＣＤ＿（１８）／ＬＦＡ－１β、ＣＤ＿（５４）／ＩＣＡＭ－１）。结合淋巴细胞变化对ＳＬＥ作进一步探讨。结果发现ＳＬＥ活动期ＣＤ＿（１１ａ）、ＣＤ＿（１８）表达随ＣＤ＿４细胞减少而降低、ＣＤ＿８细胞增多而增高，ＣＤ＿（５４）在ＣＤ＿（２０）细胞上亦增高。此外，ＣＤ＿８细胞的ＣＤ＿（１８）增高与ＣＤ＿４ＣＤ＿（４５）ＲＡ￣＋细胞降低呈负相关（Ｐ＜０．０５），而与ＣＤ＿（２０）细胞的ＣＤ＿（５４）增高呈正相关（Ｐ＜０．０１）。提示粘附分子可能在ＳＬＥ发病机理中具有重要意义。     

SEQUENTIAL STUDY OF BACTERIAL ANTIBODY LEVELS ANTIBODY LEVELS AND FAECAL FLORA IN RHEUMATOID ARTHRITIS PATIENTS TAKING SULPHASALAZINE

Faecal and serum samples were collected from 31 patients withactive RA during treatment with the DMARD sulphasalazine (SASP).These were examined for changes in faecal flora and antibodiesto bacterial antigens respectively. Faecal counts of Clostridiumperfringens but not Escherichia coli or total aerobic or anaerobiccounts fell significantly after 2 weeks of treatment, this decreasebeing maintained throughout the treatment period. There was,however, no relationship between changes in the faecal carriageof this micro-organism and response to drug treatment, as assessedusing clinical and biochemical indicators of disease activity.Changes in antibody levels to antigen preparations of this organismwere also unrelated to response to drug treatment. These resultssuggest that the anti-rheumatic properties of SASP are independentof its antibacterial effect on bacteria in the bowel and alsothat neither faecal carriage of, nor antibody responses to thisbacterium are involved in disease pathogenesis. Antibody levels to an antigen preparation of Cl. perfringenswere found to be significantly lower in those patients who respondwell to SASP than those patients who show poor response; thismay prove useful as a clinical marker for predicting those patientslikely to respond to SASP therapy. KEY WORDS: Sulphasalazine, Clostridium perfringens, Response     

SYNOVIAL AND SERUM LEVELS OF METHOTREXATE DURING METHOTREXATE THERAPY OF RHEUMATOID ARTHRITIS

Methotrexate (MTX) levels were studied following intravenousMTX in both serum and synovial fluid (SF) of rheumatoid arthritispatients. Two hours after injection serum MTX levels were higherthan those of SF. At 24 hours SF levels of MTX exceeded thoseof the serum, while at 72 hours both blood and SF concentrationswere undetectable. The localization of parenteral MTX in theSF may have importance in the understanding of its mechanismand site of action in rheumatoid arthritis. KEY WORDS: Synovial fluid, Cytotoxic, Pharmacokinetics, Intravenous methotrexate     

SULPHASALAZINE IN THE TREATMENT OF RHEUMATOID ARTHRITIS: RELATIONSHIP OF DOSE AND SERUM LEVELS TO EFFICACY

Previous studies of sulphasalazine in rheumatoid arthritis havechosen an empirical dose based upon its use in ulcerative colitis.In this study we compare the efficacy and toxicity of two doses(1.5 g/day and 3 g/day, 30 patients per group), and attemptto relate efficacy to serum levels of sulphasalazine and itsmetabolites. After six months 24 of the low-dose group and 20 of the high-dosegroup remained on treatment. Greater improvement was seen inthe high-dose group. When dose was expressed as mg/kg, the doseefficacy ratio became more apparent and a dose of >40 mg/kg/dayappears to confer greater benefit. No relationship was demonstrated between serum levels of sulphasalazineor its measured metabolites, and efficacy.We conclude that responseto sulphasalazine in rheumatoid arthritis is dose dependentbut does not relate to serum levels of sulphasalazine, sulphapyridine,or acetyl sulphapyridine. KEY WORDS: Rheumatoid arthritis, Sulphasalazine     

VISCOSITY OF PLASMA AND BLOOD IN RHEUMATOID ARTHRITIS

Blood rheology was studied in 130 consecutive RA outpatients,33 with and 97 without extra-articular disease (EAD), and comparedwith that in 88 blood donors. All rheological variables weresignificantly elevated in the RA patients compared with thecontrols. Painful joint count (PJC), morning stiffness (MS)and radiographic changes (RC) correlated significantly withplasma viscosity (PV), CRP, ESR and fibrinogen concentration(FC), but only in the group without EAD. Corrected blood viscosity(CBV) at a shear rate of 92/s correlated significantly onlywith MS. Multiple regression with PJC, MS and RC as dependentvariables showed significant associations of PJC with PV, MSand CRP and RC with PV. Multiple regression with PV as the dependentvariable showed significant associations with FC and IgG. RApatients with EAD had higher PV (P<0.01), CBV at 92/s (P<0.05)and ESR (P<0.05) than the RA patients without EAD. Differencesin profiles of viscosity variables between subgroups of EADin RA patients were observed. KEY WORDS: Rheumatoid arthritis, Blood viscosity, Plasma viscosity, Haematocrit, Red cell aggregation, Acute phase reactants, Fibrinogen, Erythrocyte sedimentation rate, C-reactive protein, Immunoglobulin     

INCREASED LEVELS OF OSTEOCALCIN (SERUM BONE GLA-PROTEIN) IN RHEUMATOID ARTHRITIS

Serum osteocalcin was measured by radio-immunoassay in 56 patientswith rheumatoid arthritis (RA), and in 50 controls. Mean serum osteocalcin levels were significantly higher in patientswith RA. There was a positive correlation between osteocalcinand fasting mucopolysaccharide/creatinine ratio in both sexes,and between osteocalcin and fasting hydroxyproline/creatinineratio in women. Serum alkaline phosphatase activity, a lessspecific marker for bone formation, was also increased in RA,and there was a positive correlation with osteocalcin in bothsexes. These data suggest that overall bone turnover is increased inRA and that serum osteocalcin may provide additional informationfor the evaluation of bone metabolism in this disease. KEY WORDS: Bone, Osteocalcin, Rheumatoid arthritis     

NAILFOLD CAPILLAROSCOPY: A BLINDED STUDY OF ITS DISCRIMINATORY VALUE IN SCLERODERMA, SYSTEMIC LUPUS ERYTHEMATOSUS, AND RHEUMATOID ARTHRITIS

The appearances of the nailfold capillaries can be used to distinguish between various connective tissue diseases. In a study of 30 patients (10 with scleroderma, nine with systemic lupus erythematosus, and 11 with rheumatoid arthritis), photographs were taken of the eight nailfolds of each patient (thumbs excluded) and then coded. Each of the photographs was later analysed by a rheumatology registrar and an attempt was made to predict the patient's diagnosis using only the appearance of the nailfold. The diagnostic specificity and sensitivity were 89% and 80%, respectively.
The results indicate that nailfold capillaroscopy, performed by a relatively inexperienced observer, can accurately distinguish between patients with scleroderma and those with systemic lupus erythematosus or rheumatoid arthritis. (Aust NZ J Med 1986; 16: 457–460.)     

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     

BLOOD AND URINE GOLD LEVELS DURING CHRYSOTHERAPY FOR RHEUMATOID ARTHRITIS

In this study the value of undertaking routine blood and urineestimations was assessed in relation to achieving maximum efficacyand safety in chrysotherapy. It was found that a favourableresponse to gold was forthcoming in approximately two-thirdsof patients and occurred irrespective of the patients' diseaseduration or severity, or the mean serum gold level or the meanurinary gold excretion, estimated immediately before the nextgold injection was due. The presence of rheumatoid nodules andthe patients' advancing age were associated with a less favourableclinical response to gold. Those patients who derived a marked benefit from chrysotherapydid so significantly earlier in their course than those whoderived only moderate benefit. A frequent correlation was seen in individual patients betweenserum gold levels and urinary gold excretion. This was mostmarked in those patients showing a favourable response to gold. ^*Paper presented at a combined meeting of the British Associationfor Rheumatology and Rehabilitation, The Heberden Society, theRheumatology and Rehabilitation Section of the Royal Societyof Medicine, and the Swiss Society for Rheumatology, Bristol,June 1974.     

PARITY AND RISK OF RHEUMATOID ARTHRITIS IN FINNISH WOMEN

Several recent case-control studies have suggested that nulliparityis a risk factor for rheumatoid arthritis (RA). We studied parityfor its association with the incidence of RA in a cohort ofadult Finnish women examined by the Mobile Clinic of the SocialInsurance Institution in 1966–72. The 15 441 women were     

FENCLOFENAC AND DICLOFENAC IN THE TREATMENT OF RHEUMATOID ARTHRITIS

A six month single-blind, randomized parallel group study comparingthe effects of fenclofenac and diclofenac in 63 patients withrheumatoid arthritis is described. Both treatments producedimprovements in clinical measurements, with a significant between-treatmenteffect in favour of fenclofenac for overall pain, night painand duration of morning stiffness. Both treatments produceda decrease in IgM and the fenclofenac group produced decreasesin plasma viscosity and ESR, the latter showing a significantbetween-treatment effect in favour of fenclofenac. No clinicallysignificant changes in routine haematology and biochemistrywere noted. Unwanted effects leading to withdrawal of therapywere reported by five patients in the fenclofenac group andthree patients in the diclofenac group. Two patients in thefenclofenac group and one in the diclofenac group were withdrawnfor reasons unrelated to therapy. In the diclofenac group twoand four patients were withdrawn for clinical deteriorationand inadequate effect respectively. KEY WORDS: Rheumatoid arthritis, Fenclofenac, Diclofenac     

EQUIANALGESIC EFFECTS OF PARACETAMOL AND INDOMETHACIN IN RHEUMATOID ARTHRITIS

The therapeutic and adverse effects of 2 weeks of treatmentwith high-dose indomethacin (150 mg/day) were compared withthose of low-dose indomethacin (50 mg/day) combined with paracetamol(4 g/day) in a double-blind, double-dummy, cross-over studyin 17 patients with active rheumatoid arthritis. Grip strength,Ritchie's index, joint circumference, joint pain, and patient'sand physician's global assessments were estimated, and conventionallaboratory parameters were followed. In addition, the time-concentrationprofiles of indomethacin and paracetamol were assessed duringsteady state. All patients had measurable plasma drug levels,indicating adequate compliance, and responders and nonresponders(five on each treatment) had equal drug levels, indicating thatthe variation in therapeutic efficacy was not secondary to pharmacokineticdifferences. While there were fewer and milder side-effectsduring treatment with the drug combination, there was no differencein therapeutic efficacy. Hence, it appears that the main therapeuticprofit of indomethacin in daily doses greater than 50 mg isenhanced analgesia. As such dosage involves pronounced side-effects,it seems more appropriate to employ the combination of 50 mgindomethacin and 4 g paracetamol, whereby similar analgesiacan be obtained without an increase in side-effects. KEY WORDS: Rheumatoid arthritis, Analgesia, Paracetamol, Indomethacin, Plasma levels.