Edward J. Pisko

Multiple myeloma presenting with primary meningococcal arthritis.

A 64-year-old white man presented with Neisseria meningitidis primary septic arthritis. Further evaluation revealed multiple myeloma. Increased susceptibility to infection occurs early in multiple myeloma; thus, a rare cause of primary septic arthritis, such as N. meningitidis, warrants a full evaluation for immunocompromise.

Pirprofen and aspirin in the treatment of rheumatoid arthritis

Pirprofen (800 mg/day) or aspirin (3,600 mg/day) was administered in double‐blind fashion for up to one yr to 40 adult outpatients with rheumatoid arthritis, after a short, single‐blind placebo period. There were no statistically significant differences in efficacy between pirprofen and aspirin, as evidenced by patient opinion, observer opinion, grip strength, walking time, number of tender joints, number of swollen joints, or erythrocyte sedimentation rate. Clinically significant pain of gastrointestinal origin occurred in an equal number of patients from each group. Audiologic evaluation revealed 3 pirprofen‐treated patients and 5 aspirin‐treated patients in whom a sensorineural hearing loss progressed during therapy and required either discontinuation or reduction of drug dosage. Ophthalmologic evaluation disclosed a high prevalence of lesions, the most common being decreased visual acuity and cataracts not explained by previous antiarthritic therapy. The high prevalence of audiologic and ophthalmologic pathology reported in the literature in patients with rheumatoid arthritis makes it difficult to establish in our study whether pirprofen or aspirin affected these organ systems.

Increased incidence of recurrent hematuria in ankylosing spondylitis: a possible association with IgA nephropathy

SummaryA retrospective analysis of our patients with ankylosing spondylitis revealed a 17.8% incidence of recurrent hematuria. Two of the five patients with recurrent hematuria had previously undergone renal biopsies showing a focal proliferative glomerulonephritis. The only specimen examined by immunofluorescent staining showed the typical changes of IgA nephropathy. A control group of patients with rheumatoid arthritis did not show recurrent hematuria. Recurrent hematuria may be a frequent occurrence in ankylosing spondylitis and may signify the presence of one of the glomerulonephritides such as IgA nephropathy.

Human rheumatoid factor producing cell induction by 2-mercaptoethanol: Immunomodulation by a simple thiol compound

Two-mercaptoethanol (2-ME), a simple 2 carbon thiol compound with a wide variety of in vitro and in vivo immunomodulating effects, was evaluated for its usefulness as a molecular probe of human antibody producing cell activation by adding 2-ME to cultures of peripheral blood mononuclear leukocytes from normal human volunteers. Culturing normal human leukocytes with 2-ME induced a significant number of cells producing rheumatoid factor as measured by a hemolytic plaque forming cell (PFC) assay. Dose response studies revealed 5 X 10(-5)M to be the optimum concentration of 2-ME for the induction of rheumatoid factor plaque forming cells (RF-PFC). This concentration of 2-ME also maximally induced PFC making antibodies to sheep red cells coupled to the trinitrophenyl (TNP) hapten demonstrating that 2-ME is a polyclonal inducer of human PFC. The addition of 5 X 10(-5) M 2-ME to cultures containing maximal concentrations of the polyclonal stimulators, pokeweed mitogen and human heat-aggregrated IgG, increased the number of RF-PFC detected in these cultures by approximately 50%, although both lower and higher concentrations of 2-ME suppressed the RF-PFC response. We conclude that 2-ME induces normal human leukocytes to produce rheumatoid factor as part of a polyclonal activation of antibody producing cells. 2-ME also has immunomodulating effects when added to other polyclonal stimulators of antibody producing cells.

Induction of Autoantibody-Producing Cells after the Coculture of Haptenated and Normal Human Mononuclear Leukocytes

Abstract The coculture of normal human peripheral blood mononuclear leukocytes (PBL) and autologous mononuclear leukocytes coupled to the trinitrophenyl (TNP) hapten (TNP-PBL) was found to induce a polyclonal activation of antibody-producing cells. The polyclonal activation of antibody-producing cells was demonstrated by detecting the induction of cells producing antibody to sheep red blood cells using a complement-dependent, direct, hemolytic plaque-forming cell (PFC) assay. A ratio of four normal to one haptenated mononuclear leukocyte was found to be optimal for inducing the polyclonal activation of antibody-producing cells in these cultures. The plaque-forming cell assay in these experiments utilized monolayers of indicator red cells. Further evidence for the polyclonal induction of antibody-producing cells by TNP-PBL was provided by demonstrating PFC on monolayers of not only sheep red blood cells, but also autologous human red cells, bromelain-treated autologous red cells, TNP-coupled human and sheep red cells, and human autologous red cells coupled to human heat-aggregated IgG with chromic chloride. Thus cells secreting antibody to TNP, human red cells, and human IgG were induced. Anti-IgG and anti-human red cell-producing cells were first detected on Day 2 of culture and were still present on Day 9. Mononuclear leukocytes altered by chemical haptenation polyclonally stimulate normal mononuclear leukocytes to become antibody-producing cells. This polyclonal stimulation of antibody-producing cells includes cells producing antibodies to human IgG and human autologous red blood cells suggesting that autoantibody-producing cells are induced.

Spontaneous and aggregated IgG induced rheumatoid factor producing cells in rheumatoid arthritis.

SummarySeropositive rheumatoid arthritis (RA) patients were found to have high numbers of spontaneously occurring cells making rheumatoid factor (RF) reactive with human IgG as measured by a RF plaque forming cell (RF-PFC) assay. There was a significant positive correlation between the number of RF-PFC and both disease activity measured by the sedimentation rate and RF titer measured by the RA latex test. Aggregated IgG and pokeweed mitogen were equally effective stimulators of RF-PFC in cultures of RA peripheral blood mononuclear leukocytes. The rheumatoid ratio of helper (T4): suppressor (T8) T lymphocytes was also significantly increased over the ratio of normal controls, but this ratio did not correlate with the number of RF-PFC. Aggregated IgG or immune complexes may be responsible for stimulating RA RF-PFC in vivo.

Vasculitis. A practical approach to management.

Vasculitis encompasses a wide variety of diseases. Because diagnosis may be difficult, a careful evaluation is essential, including a detailed patient history, thorough physical examination, and appropriate laboratory studies. Diagnosis is based on clinicopathologic features that permit identification of the condition. Biopsies are often necessary to confirm a diagnosis. It is important to accurately categorize the vasculitic disorders, since prompt, aggressive therapy with potentially toxic drugs is necessary to avoid irreversible organ system dysfunction.