NSAIDs increase risk of gastrointestinal bleeding in primary care patients with dyspepsia.

BACKGROUND: A 1-year prospective study of 545 patients with dyspepsia examined the natural history of dyspepsia in a primary care population. Predictors of gastrointestinal bleeding and other related utilization-of-service indicators were identified. METHODS: Subjects were adult primary care patients seen at a southern California county medical center. Data were collected by means of a patient questionnaire as well as from medical charts and a computerized hospital billing system. Chi-square, t test, and stepwise multiple logistic regression analyses were used to analyze the data. Outcome events were follow-up visits for any gastrointestinal event and follow-up visits for gastrointestinal bleeding specifically. RESULTS: Prior exposure to nonsteroidal anti-inflammatory drugs doubled the odds for any follow-up gastrointestinal event (odds ratio = 1.9; 95% CI = 1.4 to 2.8). Nonsteroidal anti-inflammatory drugs increased the risk for gastrointestinal bleeding by a factor of 7 (odds ratio = 7.1; 95% CI = 1.3 to 50.0). CONCLUSIONS: In a cohort of primary care patients with dyspepsia, use of nonsteroidal anti-inflammatory drugs was the most important predictor of a follow-up gastrointestinal event, both for any gastrointestinal event and gastrointestinal bleeding specifically.

The rheumatoid factor reactivity of a human IgG monoclonal autoantibody is encoded by a variant V kappa II L chain gene.

To determine the genetic and molecular basis for rheumatoid factor (RF) autoantibody reactivity in patients with destructive, erosive arthritis, we established a human lymphoblastoid cell line (hRF-1) from a patient with polyarthritis that produced an IgG RF mAb, mAb hRF-1. Studies of isolated H and L chains showed that the specificity of RF reactivity is conferred by mAb hRF-1 L chains. The L chain gene was cloned from a cDNA library prepared from hRF-1 cells. The nucleotide sequence was similar to known V kappa II L chains except for a two nucleotide change corresponding to a change of two amino acids in an invariable region of FR3. A germ-line gene with one of the nucleotide changes was identified by polymerase chain reaction in multiple cell lines, including K562 that does not rearrange Ig genes, but the other nucleotide change appeared to be due to mutation. Either or both of these amino acid changes may contribute to the RF reactivity, because an antibody with the same V kappa II L chain except for these two amino acid changes in FR3 did not have RF reactivity. The RF reactivity of isolated L chains from mAb hRF-1 was confirmed by transfecting COS cells with an expression vector encoding the hRF-1 kappa-chain and showing that the secreted k-chains had RF reactivity. Expression of this variant V kappa II L chain gene may form the basis for RF autoantibody reactivity in some patients.

Rheumatoid factors specific for active rheumatoid arthritis.

To measure rheumatoid factors specific for patients with rheumatoid arthritis an enzyme linked immunosorbent assay (ELISA) was developed to measure rheumatoid factors in human serum that bind a cross-reactive determinant shared on human and other mammalian IgG. Rheumatoid factors that cross link human IgG and sheep IgG in a double binding ELISA were almost completely specific (greater than 99%) for rheumatoid arthritis in assays of 108 sera from patients with rheumatoid arthritis compared with 231 sera from patients with other connective tissue diseases and 365 sera from healthy subjects and patients without these diseases. Moreover, positive tests occurred primarily in patients with active arthritis (r = 0.68). In contrast, these rheumatoid factor autoantibodies were not detected in sera from most of the patients with other autoimmune diseases, including patients with systemic lupus erythematosus. These results show that rheumatoid factors identified in human sera by the double binding test are specific for active rheumatoid arthritis.

A conserved anti-DNA antibody idiotype associated with nephritis in murine and human systemic lupus erythematosus.

In order to identify unique structural features of pathogenic autoantibodies to DNA in SLE, a murine anti-anti-DNA (anti-Id) mAb (mAb 1C7) was produced in response to immunization of lupus mice with a syngeneic anti-DNA mAb (mAb 3E10). Immunization of lupus mice with mAb 3E10 inhibited production of native anti-DNA antibodies, suppressed development of lupus kidney disease (nephritis), and induced production of anti-anti-DNA (anti-Id) antibodies. mAb 1C7 bound F(ab')2 fragments of mAb 3E10, and it bound other murine anti-DNA mAb, but not murine mAb or polyclonal serum antibodies unreactive with DNA. Moreover, binding of mAb 1C7 anti-Id to mAb 3E10 was inhibited by DNA, suggesting anti-Id binding within or near the binding site for DNA. Furthermore, mAb 1C7 bound serum IgG immunoglobulins from 9/12 patients with lupus nephritis and serum anti-DNA antibodies compared to only 3/12 SLE patients with comparable serum levels of anti-DNA antibodies, but without nephritis (p = 0.04), and only 1/53 SLE patients without serum anti-DNA antibodies, 0/49 patients with rheumatoid arthritis, and 1/47 healthy subjects (p less than 0.001). These results provide evidence that mAb 1C7 identifies a conserved Id associated with anti-DNA antibodies in murine and human SLE and may be useful as a structural probe to characterize pathogenic anti-DNA antibodies in SLE.

Penicillin anaphylaxis: fatality in elderly patients without a history of penicillin allergy.

Two anaphylactic fatalities following penicillin administration are reported. Neither of the two patients had a history of previous penicillin allergy. Both were elderly and suffered from active cardiovascular disease. Penicillin skin testing may be indicated in some high-risk patients requiring parenteral penicillin, despite a negative history for penicillin allergy.

Human monoclonal IgG rheumatoid factor has structural homology with bacterial Fc receptor proteins.

A cloned lymphoblast cell line, hRF-1, that secreted human monoclonal IgG4 rheumatoid factor autoantibody was produced by Epstein-Barr virus transformation of lymphocytes from rheumatoid arthritis synovium. The binding of hRF-1 rheumatoid factor to IgG globulins of different mammalian species was similar to the binding specificity of Staphylococcus aureus protein A (SpA) and to antibodies found in the sera from patients with rheumatoid arthritis. hRF-1 also had the same binding pattern to human IgG subclasses as SpA. Direct competition was observed between SpA and hRF-1 in binding IgG Fc. These results provide evidence for structural homology between a bacterial Fc receptor protein (SpA) and the monoclonal IgG rheumatoid factor.

Rheumatic manifestations of Wegener's granulomatosis.

Wegener's granulomatosis is a necrotizing granulomatous vasculitis with multisystem involvement. We reviewed the rheumatic manifestations among 50 patients with Wegener's granulomatosis. Arthralgia, myalgia and/or arthritis occurred in 2/3 of patients and 28% had nonerosive and nondeforming polyarthritis. Noninflammatory synovial fluid was found upon arthrocentesis of one patient with a knee effusion. Unexpected findings included soft tissue calcifications in 9 patients, sacroiliitis in 3, and relapsing polychondritis in 2. Rheumatoid factor was present in 1/2 of the patients tested. Additionally, both antinuclear antibodies and anti-DNA antibodies were detected in 14 and 38%, respectively, of patients tested.

Chrysotherapy in the treatment of corticosteroid-dependent asthma.

The efficacy of parenteral gold therapy was evaluated in patients with steroid-dependent asthma. Five of eight patients improved in terms of reduced steroid requirement while they were maintaining or improving lung function. Two patients developed significant proteinuria that resolved with cessation of gold. Chrysotherapy appears to have a corticosteroid-sparing effect in some patients and may have a useful role in the management of severe refractory asthma.