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Biomedical subjects

G W Cannon

Publications and source records attributed to G W Cannon.

At least 19 recordsLinked to original sources
PubMed1995

Immunologic assessment during treatment of rheumatoid arthritis with anti-CD5 immunoconjugate.

OBJECTIVE: To determine if sustained immunologic effects occurred after treatment of patients with rheumatoid arthritis (RA) with an immunoconjugate of murine anti-CD5 monoclonal antibody with ricin A chain (anti-CD5). METHODS: We measured lymphocyte populations, mitogen induced peripheral blood mononuclear cell (PBMC) stimulation, cytokine levels, immunoglobulin levels, in vivo immune function, and clinical outcomes in 9 patients with RA treated with anti-CD5. RESULTS: The treatment of patients with RA with anti-CD5 was associated with marked acute depletion of peripheral blood lymphocytes (p < 0.01) during and immediately after treatment. A sustained decrease in the number of CD3, CD4, CD5, and CD8 bearing lymphocytes persisted for 2 months after treatment (p < 0.05). After 3 months a mild decrease in the number of these lymphocyte populations persisted, but when compared to baseline values, the differences were not found to be statistically significant. Phytohemagglutinin induced PBMC proliferation was decreased at the 3-month followup (p < 0.05). Evaluations of mitogen induced cytokine and immunoglobulin production, immunoglobulin level, autoantibody, and in vivo antibody response to tetanus toxoid did not show any consistent change from baseline. CONCLUSION: Anti-CD5 treatment of RA appears to be associated with a decrease in the population of cells bearing CD5, but does not appear to induce any persistent immunologic abnormalities.

Adolescent↗
PubMed1994

Exacerbation of collagen-induced arthritis in rats by rat cytomegalovirus is antigen-specific.

Collagen-Induced Arthritis (CIA) is an experimentally induced and genetically controlled animal model of chronic joint inflammation. In rats, there are informative strain differences in susceptibility to CIA. DA rats (RT1avl) develop severe CIA after immunization with bovine (BII), chick (CII), or homologous rat (RII) type II collagens. In contrast, the MHC-congenic DA. 1N(BN) and WF.1N(BN) rats (RT1n) are relatively resistant to CIA and develop moderate CIA in response to immunization with CII but not BII or RII. We previously found that simultaneous infection with rat cytomegalovirus (RCMV) greatly exacerbates the severity of arthritis that develops in BII-immunized DA rats. To examine the mechanism of RCMV amplification of CIA, the effect of simultaneous infection with RCMV on arthritis and autoimmunity to type II collagen was determined in WF.1N and DA.1N rats after immunization with BII, CII and RII. RCMV increased the incidence of CIA and the level of autoimmunity to type II collagen (skin-testing and IgG antibody titer) selectively in DA.1N and WF.1N rats immunized with CII, but not in littermates immunized with BII, although the transient reversal of CD4+/CD8+ mononuclear cell ratios in peripheral blood that is associated with RCMV infection occurred equally in both BII- and CII- immunized DA.1N rats. Likewise, RCMV infection moderately increased the levels of anti-RII autoimmunity and arthritis in DA rats sub-optimally immunized with RII but had no consistent effect on either anti-RII immunity or arthritis in RII-immunized DA.1N and WF.1n rats. The data show that RCMV augments arthritis only in rats that are genetically susceptible to CIA and that are appropriately immunized with a species of type II collagen that is arthritogenic for the MHC-haplotype being tested. Two possible mechanisms are suggested by these data: RCMV-associated increases in anti-RII autoimmunity in rats with CIA may result from amino acid sequence homologies between RCMV and type II collagen; alternatively, virus-induced pro-inflammatory cytokines may activate RII-reactive lymphocytes thereby potentiating autoimmunity and arthritis.

Animals↗
PubMed1993

Effects of administration of an anti-CD5 plus immunoconjugate in rheumatoid arthritis. Results of two phase II studies. The CD5 Plus Rheumatoid Arthritis Investigators Group.

OBJECTIVE: To evaluate the safety and activity of an immunoconjugate of ricin A chain and anti-CD5 monoclonal antibody (anti-CD5 IC), with and without concomitant methotrexate and/or azathioprine, in the treatment of rheumatoid arthritis (RA). METHODS: Seventy-nine patients with active RA were enrolled in 2 prospective open-label protocols. RESULTS: Using composite criteria, response rates were 50-68% at 1 month and 22-25% at 6 months. Transient depletion of CD3/CD5 T cells was observed on days 2 and 5 of treatment, with reconstitution on day 15 or day 29. Treatment-associated adverse effects were common but resolved rapidly without sequelae. CONCLUSION: These findings suggest activity of anti-CD5 IC in active RA and warrant confirmation in a multicenter randomized study (currently underway).

Adult↗
PubMed1992

Immunogenetics of collagen-induced arthritis in rats. Both MHC and non-MHC gene products determine the epitope specificity of immune response to bovine and chick type II collagens.

Seven inbred, RT1-congenic rat strains were immunized with native bovine (BII), porcine (PII), or chick (CII) type II collagen and observed for onset, incidence, and severity of arthritis. Clinical results were compared with IgG reactive with native rat type II collagen (RII) and the purified, renatured cyanogen-bromide peptides of BII, CII, or RII. Immunodominant responses to CB11, CB9,7, and CB12 of RII were identified. Secondary responses to CB8 and CB10 also occurred. Reproducible patterns of peptide reactivity were defined in each strain and reflected both RT1 and non-RT1 genotypes plus the species of immunizing collagen. BN non-RT1 gene products moderated clinical arthritis but increased the levels of reactivity to CB11 in three strains carrying RT1l,n,av1 haplotypes. WF (RT1u) rats were susceptible to collagen-induced arthritis (CIA) and developed very high levels of autoantibodies with dominant responses to rat CB11 after CII injections and to rat CB11 and CB9,7 after BII injections. DA (RT1av1) rats developed the most severe arthritis but had only moderate (total) levels of anti-RII IgG: a broad response to CB11, CB10, and CB9,7 after CII injections but predominantly to CB12 and CB9,7 after BII injections. Three RT1n strains--DA.1N(BN), WF.1N(MAXX), and BN--were resistant to BII-induced CIA but developed mild arthritis after immunization with CII. After BII: BN IgG reacted with CB9-7, CB11, and CB12; DA.1N and WF.1N IgG reacted with CB9,7 and CB12. After CII: BN IgG reacted broadly with CB11, CB9-7, CB12, and CB8; WF.1N IgG reacted to CB9-7, CB11, CB8, and CB12; DA.1N IgG reacted with CB8, CB11, and CB9-7. Thus, selective induction of CIA in BN, WF.1N, and DA.1N rats by CII correlated with serum IgG reactivity to rat CB11, but overall strain results identified no single cyanogen-bromide peptide as expressing the sole "arthritogenic" epitope in CIA.

Animals↗
PubMed1992

The effects of flurbiprofen on the passive transfer of adjuvant-induced arthritis.

The effect of flurbiprofen on the passive transfer of adjuvant-induced arthritis was studied to determine if flurbiprofen acted in the donor and/or recipient arms of this model. Groups of donor and recipient rats were treated with either placebo or flurbiprofen 4 mg/kg. Joint scores were markedly decreased in recipient rats treated with flurbiprofen irrespective of the whether donor animals were treated with placebo or flurbiprofen (p less than 0.01). There was also a moderate decrease in the ability of donor cells from rats treated with flurbiprofen to suppress the severity of arthritis (p less than 0.01); however, this effect was less marked than that seen in recipient animals. These data imply that flurbiprofen may act at multiple sites in adjuvant-induced arthritis, but the major site of action of flurbiprofen in this model is in the recipient animals.

Animals↗
PubMed1991

Long-term methotrexate therapy for rheumatoid arthritis.

A retrospective review of methotrexate (MTX) treatment assessed the clinical course in 124 rheumatoid arthritis (RA) patients. After 5 years, 39 (31%) patients continued MTX with clinical benefit. Although patients continuing MTX after 5 years were younger (45 +/- 13 v 54 +/- 12 yrs, P less than .001) and had a shorter disease duration of RA (9.3 +/- 8.1 v 14 +/- 11 yrs, P less than .05) than patients who discontinue the drug, these differences were not considered clinically significant. MTX was discontinued in 20 patients for a lack of clinical benefit, in 21 patients for non-drug-related reasons, and in 44 patients for suspected adverse drug reactions. The adverse drug reactions requiring permanent discontinuation of MTX were nausea, stomatitis, hair loss, rash, pulmonary reactions, elevated liver enzymes, hematologic abnormalities, and hepatic fibrosis. At least one adverse drug reaction was reported by 115 (93%) patients receiving MTX, but the majority did not require permanent drug discontinuation. Although the prevalence of adverse reactions increased with longer duration of therapy, no differences existed in the type of reactions reported over 5 years of treatment. There were no risk factors identified that were clearly associated with the development of toxicity. Long-term therapy was primarily limited by adverse reactions rather than loss of efficacy.

Adult↗
PubMed1990

Effects of indomethacin, cyclosporin, cyclophosphamide, and placebo on collagen-induced arthritis of mice.

The long term effects of indomethacin, cyclosporin, cyclophosphamide, and placebo on collagen-induced arthritis in mice were tested under two different treatment protocols. A prophylactic experiment examined the effects of the daily drug administration for 180 days beginning one day before the first collagen injection. Under this dosage schedule, cyclophosphamide and cyclosporin decreased the severity of arthritis, while indomethacin did not. A therapeutic protocol examined the effects of these same drugs when daily administration was delayed until the animals had active disease at 78 days after the first collagen injection. Under this protocol, all three drugs reduced the progression of disease. In both protocols, the most significant suppression of arthritis was seen in animals receiving cyclophosphamide which was associated with a decrease in anti-collagen antibody levels. Collagen-induced arthritis in mice should be further investigated as a model to study the long term effects of "slow-acting" anti-rheumatic drugs.

Animals↗
PubMed1990

Pulmonary complications of antirheumatic drug therapy.

Drug-induced pulmonary disease should be considered in all patients receiving these antirheumatic agents who develop new pulmonary symptoms. When a drug reaction is suspected, the possible offending agents should be discontinued, required respiratory support instituted, and infection or other pulmonary processes excluded. Pathological evaluation by lung biopsy may be needed to define the disorder and rule out infection. Treatment with corticosteroids should be considered in patients with acute pneumonitis. While significant morbidity and even death may occur with drug-induced pulmonary disease, prompt evaluation and treatment of these disorders often results in complete resolution of the process.

Anti-Inflammatory Agents↗
PubMed1990

Liver histology in patients receiving low dose pulse methotrexate for the treatment of rheumatoid arthritis.

The liver histology of 52 patients treated with intermittent low dose pulse methotrexate for rheumatoid arthritis was evaluated using a modification of the Roenigk grading system. Patients studied had had an average of 3.2 years of treatment or had received 1.7 g methotrexate. No patient had cirrhosis; 15 (29%) patients had evidence of mild fibrosis. Histological abnormalities were not predicted by liver function test changes, with the exception that hypoalbuminaemia occurred in 60% of those with grade IV (modified criteria) findings. The need for liver biopsy in patients with rheumatoid arthritis treated with methotrexate before two years or 1500 mg of treatment has not been established. Whether serial liver biopsies will be needed beyond this time has yet to be determined.

Adult↗
PubMed1990

Clinical and laboratory outcomes during the treatment of rheumatoid arthritis with methotrexate.

Ten clinical and three laboratory outcomes were evaluated in 86 patients completing a double-blind placebo-controlled trial of methotrexate in rheumatoid arthritis. The improvement in all measured outcomes was statistically significantly better in patients receiving methotrexate than in patients receiving placebo. The correlations of the changes in outcome measures were calculated to determine if improvement in one parameter was associated with improvement in other clinical parameters. Associations between different clinical outcomes were often statistically significant. Associations between laboratory outcomes were also often statistically significant. However, the association between clinical outcomes and laboratory outcomes was generally poor.

Arthritis, Rheumatoid↗
PubMed1990

Prospective two-year followup of recombinant interferon-gamma in rheumatoid arthritis.

Seventy patients with rheumatoid arthritis (RA) completing a 12-week multicenter double blind trial comparing recombinant human interferon-gamma (r-IFN-gamma) with placebo were enrolled in a longterm prospective protocol evaluating r-IFN-gamma in RA. Forty (57%) patients after 1 year and 26 (37%) patients after 2 years continued the drug with sustained clinical benefit. Over 2 years, r-IFN-gamma was discontinued in 44 patients (lack of efficacy--25, withdrawn consent--7, noncompliant--4, suspected adverse drug reactions--2, concurrent illness--6). Two years of treatment with r-IFN-gamma were well tolerated with sustained clinical benefit in some patients with few significant adverse drug reactions.

Arthritis, Rheumatoid↗
PubMed1990

Inhibition of the passive transfer of adjuvant induced arthritis by gold sodium thiomalate.

The effect of gold on the passive transfer of adjuvant induced arthritis was studied to determine if gold acted in the donor and/or recipient arms of this model. Joint scores were markedly decreased in rats receiving spleen cells from donor animals treated with gold (p less than 0.01) suggesting that gold injections alters the development and/or function of the spleen cells from these animals which transfer adjuvant induced arthritis. Gold treatment of recipient animals had little effect on subsequent arthritis.

Animals↗
PubMed1990

In vivo administration of interferon-gamma to patients with rheumatoid arthritis decreases numbers of circulating B cells.

We evaluated the expression of leukocyte cell surface antigens in patients with rheumatoid arthritis (RA) and healthy individuals using monoclonal antibodies and flow cytometry. Both 1 and 2-color analyses were performed. Markers evaluated included markers of T and B cell subsets, activation antigens, and antigens expressed on additional cell types. No major differences were seen between healthy persons and patients. The effects of in vivo administration of interferon-gamma (IFN-gamma) were studied in a clinical trial of the efficacy of this agent in the treatment of RA. Numbers of circulating B cells fell with administration of IFN-gamma. Expression of HLA-DR antigens on monocytes may have increased slightly with IFN therapy. There was no correlation between clinical response to IFN-gamma and change in any immune variables. Because of the observed alterations in B cell numbers, serum immunoglobulins were measured by radial immunodiffusion. There was no alteration of levels of most immunoglobulin isotypes as a result of therapy. There was a modest increase in serum IgA. There was no change in either rheumatoid factor or antinuclear antibody titers during IFN-gamma therapy.

Antibodies, Monoclonal↗
PubMed1989

Double-blind trial of recombinant gamma-interferon versus placebo in the treatment of rheumatoid arthritis.

One hundred five patients were enrolled in a 12-week, randomized, prospective, double-blind, placebo-controlled trial of recombinant human gamma-interferon (rHu gamma-IFN) for the treatment of rheumatoid arthritis. Fifty-four patients received rHu gamma-IFN and 51 received placebo. Forty-two patients in each group completed the 12-week trial. Some clinical improvement occurred in both groups of patients. Although the improvement with rHu gamma-IFN was greater than that with placebo, the differences were generally not statistically significant.

Adult↗
PubMed1989

Methotrexate therapy in rheumatoid arthritis: 2-year retrospective followup study.

Clinical and laboratory data in 124 patients with rheumatoid arthritis treated with methotrexate (MTX) were retrospectively reviewed over the initial 2 years after the start of treatment. Clinical improvement occurred in 103 (83%) patients after 12 weeks of treatment. At 2 years of followup, 60 patients (48%) continued to receive MTX with sustained clinical benefit. It has been discontinued in 64 (52%) patients (adverse drug reactions in 38, lack of clinical benefit in 15, and miscellaneous reasons in 11). Patients with adverse drug reactions had higher initial serum creatinine and blood urea nitrogen values than patients without adverse drug reactions.

Adult↗
PubMed1988

Peripheral lymphocyte depletion in gold sodium thiomalate-treated rheumatoid arthritis patients.

It has been reported that gold sodium thiomalate treatment of rheumatoid arthritis reduces the number of peripheral blood lymphocytes. In a prospective, double-blind, randomized trial comparing gold sodium thiomalate, auranofin, and placebo in the treatment of rheumatoid arthritis, we investigated absolute lymphocyte counts. We found that peripheral lymphocyte counts decreased, but there was no correlation with clinical change in disease activity.

Arthritis, Rheumatoid↗