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Sera from 61 patients with primary biliary cirrhosis (PBC) and 23 patients with primary Sjögren's syndrome (pSS) were tested for the presence of autoantibodies to 15 different antigens (PDH, RNP, SS-A, SS-B, Sm, Scl-70, H2AH2B, Jo-1, collagen-type I, GBM, GM <--> 1, Sulf, GD1b, MPO, PR3). Patients with pSS had significantly (p < 0.01) higher frequencies of antibodies to SS-A, SS-B and RNP (78%, 52%, 22% vs 29%, 20%, 5%, respectively) when compared to patients with PBC. On the other hand, patients with PBC had significantly (p < 0.01) higher frequencies of antibodies to PDH, Sm, Jo-1, collagen and MPO (80%, 34%, 26%, 52%, 67% vs 13%, 9%, 13%, 13%, 9%, respectively) as compared with patients with pSS. For all the other autoantibodies, no significant differences were found between PBS and pSS patients. These data on the similarities in autoimmunity between two diseases with different clinical presentations shed more light on the mosaic of autoimmunity.

The presence of antineuronal antibodies was compared in 43 patients with primary aPLS and 57 patients with neuropsychiatric SLE. Fifty-eight patients with Guillain-Barré syndrome and 72 normal healthy donors served as control groups. Seventeen patients in the study group had aPLS associated with CNS involvement. Antineuronal antibodies were studied in the sera employing a novel flow cytometric assay. The frequency of antineuronal antibodies in patients with aPLS and CNS involvement was not significantly different from that of patients with aPLS without CNS disease or from that found in the control groups (12%, 19% and 7%, respectively). However, it was significantly different from that found in SLE patients with CNS involvement (60%) (P < 0.001). Our results provide further evidence that unlike CNS-SLE, the major mechanism of CNS involvement in patients with primary aPLS might not be autoantibody (antineuronal) mediated, but rather 'thrombotic' in origin, or due to yet unknown factors.

Objective: To determine whether anti-Ro antibodies are associated with gold induced side effects., Methods: A retrospective chart review of 208 patients with rheumatoid arthritis (RA) and examination of sera for the presence of anti-Ro antibodies by enzyme linked immunosorbent assay., Results: Anti-Ro antibodies were detected in 44 (21%) of our patients with RA and their presence correlated with positive rheumatoid factor, antinuclear antibody, and secondary Sjögren's syndrome. Thirty-three out of 48 patients with gold induced side effects (69%) were anti-Ro positive in contrast to 11 patients (7.5%) with positive antibodies with no side effects (p < 0.001). Mucocutaneous reactions had the only significant correlation (p < 0.01) with the presence of anti-Ro antibodies., Conclusion: Patients with RA with anti-Ro antibodies are prone to develop mucocutaneous side effects to gold salts.

A patient with long-standing psoriatic arthritis developed an arthropathy of the hands characterized by subluxations of the metacarpophalangeal joints without erosive changes. This is to the best of our knowledge the first reported case describing Jaccoud's arthropathy associated with psoriatic arthritis.

Forty-nine members of 4 families with multiple cases of rheumatoid arthritis (RA) were investigated. Nine patients with RA, one patient with primary Sjögren's syndrome (SS) and one patient with systemic lupus erythematosus (SLE) were detected among them. Anti-Ro (SSA) antibodies were found in 11 members (22%) of the investigated group; 6 suffered from RA, SLE or primary SS, and 5 were healthy first degree relatives. Anti-La (SSB) antibodies were detected in only one family member with primary SS. Secondary SS was evident in 5 patients with RA, 3 of whom had anti-Ro antibodies; HLA-DR4 was present in 7 of 9 patients with RA (78%) but in only 7 of 26 asymptomatic relatives (27%) (p less than 0.05). All patients with RA and their relatives who had anti-Ro antibodies were found to have HLA-DR4. Our results demonstrate that anti-Ro antibodies are present in relatives of patients with RA and are strongly associated with HLA-DR4.

Forty-one patients with rheumatoid arthritis were treated for 2 weeks at a Tiberias spa hotel. Randomized into 2 groups, Group 1 received a combination of mineral baths and mud packs, and Group 2 had tap water baths only. Both groups had a significant but temporary improvement in Ritchie index. Group 1 showed a significant improvement in grip strength. No improvement was noticed in morning stiffness, 15 meter walk time and laboratory variables of disease activity in either group. Twelve patients with osteoarthritis (OA) received 2 weeks of treatment with mineral baths and mud packs. Statistically significant improvement for a period of 6 months was noticed in night pain, pain on passive motion, tenderness on palpation and in the index of severity of OA of the knee.

A case is presented of a late solitary pulmonary metastasis from a choroidal melanoma, simulating primary bronchogenic carcinoma. The pattern of metastatic choroidal melanoma and the mode of therapy are discussed.

Antibodies to native human Type I + III collagen were measured by a radioimmunoassay in sera samples of 42 rheumatoid arthritis (RA) patients. Sixteen patients (38%) had significant antibody titers. Although the frequency of HLA-DR antigens of RA patients did not differ from that of the random Israeli population, there was a significant association (P less than 0.01) between the presence of collagen antibodies and HLA-DR4.

Abnormal liver function was found in 34 (52%) of 67 young adults with measles; 5 of them (7%) also had a rise in bilirubin levels accompanied by icterus. Awareness of liver involvement in measles has been steadily increasing; consideration should be given to hepatitis as a possible complication of measles in young adults.

A case of angioimmunoblastic lymphadenopathy with pulmonary involvement is presented. The radiographic and computerized tomographic findings included multiple opacities, predominantly basal, of variable size. Associated pleural opacification was verified on both the chest roentgenogram and the computerized tomographic (CT) examination. The entity may mimic many more common clinical disease states and final diagnosis can only be established histologically.

High-dose leucovorin (folinic acid) supplementation was tested in a prospective, unblinded manner for 4 weeks in 7 rheumatoid arthritis patients who were being treated successfully with low-dose methotrexate (MTX). Nausea caused by MTX disappeared; however, the underlying rheumatic disease worsened in all patients. Subjective clinical assessment, Ritchie articular index, grip strength, erythrocyte sedimentation rate, and levels of C-reactive protein showed statistically significant deterioration. All these parameters improved after the leucovorin was stopped. This is the first direct clinical evidence implying folate antagonism in the action of low-dose MTX therapy in rheumatoid arthritis patients.

Abdominal fat tissue aspirates from 20 patients with biopsy-proved amyloidosis were investigated by polarized microscopy after staining with Congo-red. Positive results were obtained in 4 of 5 patients with primary amyloidosis (AL) and in none of 15 with amyloidosis (AA) of Familial Mediterranean Fever (FMF). We suggest that although this technique is simple, safe and effective in other forms of amyloidosis, it cannot be used as a diagnostic tool in FMF patients suffering from amyloidosis.

Three women with classic rheumatoid arthritis, who were receiving weekly doses of methotrexate (MTX), developed accelerated subcutaneous nodulosis, despite good response to the drug. In 2 of the patients, the onset of nodulosis occurred within 3 months and 5 months, respectively, after starting MTX; in the third patient, it was observed only after 4 years of MTX therapy. In all 3 patients, the onset was unusually abrupt, with extensive distribution and remarkable nodule size. Additional manifestations of cutaneous vasculitis in 2 of the patients and Raynaud's phenomenon in the third appeared concomitantly with the nodulosis. Physicians prescribing MTX therapy for patients with rheumatoid arthritis should be aware of these potential complications.

Sequential daily measurements of erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) were performed for one week after an I.V. injection of 7.5-13 mg methotrexate (MTX) in 18 patients with rheumatoid arthritis. Early decreases of ESR and CRP were observed. Serum CRP was more sensitive than ESR, displaying more pronounced falls from baseline to both the minimal and to the 7th day levels. Patients receiving their first dose of MTX (n = 9) exhibited a more prominent reduction of CRP levels in comparison to veteran MTX users (n = 9). The prompt response of acute phase reactants to MTX may correspond to the relatively rapid clinical effect of the drug in RA. It may also support an antiinflammatory mechanism of action of low dose MTX.

Methotrexate (MTX) levels were studied following intravenous MTX in both serum and synovial fluid (SF) of rheumatoid arthritis patients. Two hours after injection serum MTX levels were higher than those of SF. At 24 hours SF levels of MTX exceeded those of the serum, while at 72 hours both blood and SF concentrations were undetectable. The localization of parenteral MTX in the SF may have importance in the understanding of its mechanism and site of action in rheumatoid arthritis.

Purpura fulminans is a rare disease of childhood, manifested by massive hemorrhage into the skin, widespread thrombosis of venules and arterioles and a hematologic picture of disseminated intravascular coagulation. An unusual case in a 68-year-old man is presented and the mode of therapy discussed.

Bronchoalveolar lavage (BAL) was performed to assess the nature of pulmonary involvement in 12 asymptomatic nonsmoking patients with rheumatoid arthritis (RA). All 12 patients had normal lung function tests, including diffuse capacity for carbon monoxide and normal blood gases. Four patients (33%) had mild basilar interstitial changes on chest radiographs. In these 4 patients an elevated lymphocytic count in BAL fluid (30.7 +/- 8.3%) was found, as compared to the 8 patients with normal chest roentgenograms (7.2 +/- 1.9%; p less than 0.001). We suggest that BAL may be used as a sensitive tool for early diagnosis of pulmonary involvement in patients with RA.

Nifedipine, a calcium-channel blocking agent, has been reported to cause many side effects, particularly in the cardiovascular system. A case of nifedipine-induced hypokalemia is presented, with a discussion on the presumable mechanism involved in this phenomenon.

A number of alpha-ketophosphonates have been prepared and their enol-keto tautomerism has been studied by means of proton and phosphorus NMR and infrared spectroscopy and the ferric chloride test. Aliphatic ketophosphonates exist largely in the keto tautomeric forms, with only a small amount of enol forms present. All the aromatic acylphosphonates studied, however, enolize extensively. An x-ray analysis confirmed enolization and E configuration as the only stereochemical isomer. Reaction of diazomethane with diethyl p-methoxyphenylacetyl phosphonate gave a mixture of O-methylation and carbene insertion products, whereas the same reaction with diethyl isobutyryl phosphonate gave only carbene insertion products.

Two patients with classical rheumatoid arthritis and a mild nondeforming relapsing polychondritis are presented. DR4 antigen and depressed C4 levels were found and possible autoimmune mechanisms are discussed. The need for specific questioning to detect this rare association is proposed.

The platelet calcium content, the plasma calcium level and the serum digoxin were examined in 90 individuals divided into the following four groups : I -- patients with digoxin intoxication; II -- treated with digoxin; III -- treated with digoxin and furosemide, and IV -- control subjects. The patients with digoxin intoxication showed a lower platelet calcium content as compared to subjects of the other groups (p less than 0.001), whereas the serum digoxin level was significantly higher than in the patients of groups II and III (p less than 0.001). Since the examination of the platelet calcium level is a relatively simple and rapid procedure, with reliable results, its use as a routine method in the determination of digoxin intoxication is suggested.

Agaridoxin, a catecholamine isolated from mushrooms, and 4 synthetic analogues cause activation of adenylate cyclase in the presence of guanylyl imidodiphosphate (Gpp(NH)p) in membrane particles prepared from rat hypothalamus. These compounds also activate adenylate cyclase preparations from rat kidney, liver and cerebral cortex. In the presence of tyrosinase, these compounds are readily oxidized to quinones which lack agonist activity. Studies with selective adrenergic blockers suggest that agaridoxin acts at an alpha 1-type receptor. Agaridoxin-mediated adenylate cyclase stimulation is most effectively antagonized by WB-4101 and phenoxybenzamine, while propranolol and yohimbine are without inhibitory effect. Agaridoxin and the alpha 1 agonist methoxamine inhibited the binding of [3H]WB-4101 in rat hypothalamic and cerebral cortical membranes. The values of Ki for both compounds are lower than that of norepinephrine. The agaridoxin analogue, 4-aminocatechol hydrochloride, is a more effective and potent adenylate cyclase activator than agaridoxin or methoxamine.

Two antibiotics isolated from a culture MA-2465 were identified as aureothin and labilomycin, the chemical structures of which had been reported previously. It was also concluded that mycolutein and pulvomycin isolated as antibiotics in 1955 and 1957 respectively are also identical with aureothin and labilomycin. A cursory study of MA-2465 indicates that it is distinctly different from the culture which was first observed to produce labilomycin and is probably different from the organism first noted to produce aureothin.

The coincidence of skin eruption and remission induced by gold has not previously been reported. In 50 out of 247 patients with rheumatoid arthritis treated with gold salts (Solganal) between 1977 and 1987 treatment was stopped owing to adverse reactions. Skin rashes were present in 31 patients, 10 had nephropathy, and nine patients had aphthous stomatitis. All 31 patients who developed skin eruption entered a concomitant clinical and laboratory remission. The remission satisfied the American Rheumatism Association preliminary criteria and was accompanied by a significant decrease of mean erythrocyte sedimentation rate from 43 (SD 13) to 25 (11) mm/h. Disease was exacerbated in 23 patients after three to 60 months. Eight patients are in remission at present, five to 68 months after gold treatment was discontinued. In contrast, no remission was noticed among the 19 patients with nephropathy or stomatitis.

A 62-year-old woman presenting with a clinical picture of acute cholecystitis was found to have lymphoma upon pathological examination of the gallbladder. Such a presentation of large-cell non-Hodgkin's lymphoma is unique and has not been described before.

In a prospective open study 44 Israeli patients with rheumatoid arthritis were treated with weekly low dose methotrexate (MTX) for up to 36 months. Nine patients withdrew from the study: six because of side effects and three due to inefficacy. One patient died of septicaemia following septic arthritis. Significant improvement, graded by Ritchie articular index, grip strength, physician's global assessment, erythrocyte sedimentation rate (ESR), and platelet counts, was noticed in response to treatment. Seronegative patients had a better clinical response. Transient gastrointestinal symptoms were common and correlated with increases of serum aspartate transaminase (AST). HLA-DR1 and DR7 were significantly associated with increased serum AST concentrations.

C-reactive protein levels were measured in sera of 111 patients with rheumatoid arthritis and were compared with erythrocyte sedimentation rate. The patients were divided into six groups according to drug therapy. Comparison between the groups suggests that CRP correlates best with ESR in patients treated with penicillamine and in patients in clinical remission. Patients treated with gold, NSAID or methotrexate have a weaker correlation between the two parameters, while steroid therapy yields the poorest correlation which is not statistically significant. Our data suggest that although CRP is a sensitive index of disease activity, the specific drug taken by the patient must be considered before interpreting the results.