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Biomedical subjects

M Harth

Publications and source records attributed to M Harth.

At least 55 records · Page 3Linked to original sources
PubMed1994

Superoxide production from cytokine-treated adherent rheumatoid neutrophils.

We have compared superoxide (O2-) production from cytokine-treated rheumatoid arthritis (RA) vs. control neutrophils (PMN). Exposure of adherent peripheral blood PMN to cytokines known to be present in RA joints (IL-1 beta, TNF-alpha, GM-CSF) resulted in enhanced O2- production from both RA and controls. With few exceptions, we did not find significant differences in enhanced O2- production, between RA and controls. By enhancing O2- production from PMN adherent to articular cartilage, cytokines may influence the potential for joint damage in RA.

Adult↗
PubMed1993

Arthritis in hemochromatosis.

We reviewed the clinical and radiographic features of arthropathy in 25 subjects with hemochromatosis, 16 probands and 9 discovered homozygous relatives. Clinical arthritis was present in 15/16 probands and 1/9 discovered homozygotes (p < 0.005). Radiologic evidence of arthropathy was seen additionally in 2 asymptomatic discovered homozygotes. The metacarpophalangeal joints and wrists were most commonly involved; severe hip disease occurred in 6. Patients with clinical or radiologic arthropathy were older than patients without. Arthropathy occurred in all 4 female probands, but in none of the 3 female discovered homozygotes. Chondrocalcinosis was seen in 9 subjects but was usually asymptomatic. The arthritis of hemochromatosis may be difficult to differentiate from several other joint diseases, especially calcium pyrophosphate dihydrate deposition disease.

Adult↗
PubMed1992

Mechanisms of action of disease modifying antirheumatic drugs.

The relationship between the biologic activities of disease modifying antirheumatic drugs (DMARD) and their therapeutic effects are complex. Some DMARD are prodrugs, e.g., azathioprine; others may act in combination with endogenous substances, e.g., D-penicillamine and copper salts. Gold compounds, antimalarials, sulfasalazine, azathioprine and methotrexate affect various phagocytic cell functions. Most DMARD inhibit the immune responses of monocytes and of T and B lymphocytes. Gold, sulfasalazine, D-penicillamine also affect fibroblast and/or endothelial cell proliferation. Many DMARD inhibit responses to, or production of, cytokines. Several DMARD have overlapping biologic effects but differ in their therapeutic efficacy in individual patients for unknown reasons.

Anti-Inflammatory Agents↗
PubMed1991

Cytokine production and lymphocyte transformation during stress.

The production of interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN gamma) and blast transformation in peripheral blood mononuclear cells were assessed in medical students writing an academic examination. Blood samples were obtained on three occasions: (1) 1 month prior to the examination during a period of relatively low academic demand; (2) immediately after the examination; and (3) 10 days later. Results indicated that immune responses were significantly different immediately after the examination compared with the baseline and postexam measures. Lymphocyte responsiveness to both concanavalin A and pokeweed mitogen was decreased, as was the production of IFN gamma, supporting earlier reports of immunosuppression after relatively commonplace stressors. In contrast to predictions, IL-1 beta production was significantly elevated after the examination. Cortisol levels were also measured, but did not change across the three sample points. Our finding of an increase in IL-1 beta production suggests that stress may have different effects on different cell populations by enhancing the responses of monocytes and depressing those of lymphocytes.

Adult↗
PubMed1991

Reconstitution of impaired autologous mixed lymphocyte reactivity in rheumatoid arthritis.

We examined the ability of recombinant IL-2 to reconstitute the autologous mixed lymphocyte reaction (AMLR) defect in peripheral blood mononuclear cells (PBM) from patients with rheumatoid arthritis (RA). Our results revealed an ability to fully reconstitute RA AMLRs with pharmacologic concentrations (100 units/ml), but not physiologic concentrations (10 units/ml) of IL-2. Full reconstitution of RA AMLRs was achieved whether IL-2 was added as the initiation of culture or at 48 or 72 hours prior to termination of the cultures. Impaired IL-2 production was noted throughout the time course of the RA AMLRs. Neither an inhibitor of IL-1 nor IL-2 was detected in AMLR culture supernatants. Moreover, IL-1 in pharmacologic concentrations up to 50 units/ml failed to reconstitute impaired AMLR reactivity. In 2 patients whose AMLRs failed to reconstitute fully with 100 units/ml IL-2, addition of 10 units/ml IL-1 in combination with IL-2 fully reconstituted the AMLR defect. The results may suggest that defective IL-2 generation alone cannot fully account for impaired AMLR reactivity in RA patients.

Arthritis, Rheumatoid↗
PubMed1991

Adult Still's disease: manifestations, disease course, and outcome in 62 patients.

Clinical and laboratory manifestations, disease course, outcome, and HLA associations were studied in an inception cohort of 62 subjects with adult Still's disease (ASD) from 5 Canadian universities. Twenty-eight patients (45%) were female and the median age at disease onset was 24 years. In general, the clinical features observed in our patients were identical to those in other published series. However, significantly higher frequencies of sore throat (92%), weight loss (76%), lymphadenopathy (74%), pleuritis (53%), pneumonitis (27%), and abdominal pain (48%) were noted in our patients compared to those in a recent literature review. Liver involvement with hepatomegaly (44%) or abnormal liver function tests (LFTs) (76%) was common and was responsible for the 2 deaths attributed to Still's disease in our series. Severe liver failure always occurred in conjunction with aspirin or NSAID therapy. Therefore, whether or not aspirin or other NSAIDs are used, we recommend close monitoring of LFTs in patients with ASD, especially early in the disease course. Laboratory manifestations were similar to those already reported. Leukocytosis (greater than or equal to 15,000/mm3) was present in 50 patients (81%), a normochromic, normocytic anemia (hemoglobin less than or equal to 10 g/dl) in 42 (68%), and an elevated ESR in all. The mean follow-up of the 62 patients was 70 months (range, 2-163). Twenty-one patients (34%) had a self-limited disease course, 15 (24%) an intermittent course, and 22 (36%) a chronic disease course. Four patients (6%) died, and 2 of these deaths were attributed to Still's disease. For those patients who experienced a recurrence of ASD, the flares were usually of shorter duration and milder in severity than the initial episode. No initiating factor for disease exacerbation was identified in our patients. Although 22 of 62 patients (36%) had a chronic disease course, 52 (90%) were in ARA Functional Class I, and only 4 and 2 patients were in ARA Functional Class II and III, respectively. Patients with Still's disease had higher scores than the controls on the Pain (P less than 0.01) and Physical Disability (P less than 0.05) subscales of Arthritis Impact Measurement Scales health status questionnaire. Joint radiographs performed at the follow-up evaluation disclosed typical carpometacarpal and intercarpal involvement in 16 of 39 patients. In our series, HLA-B17, B18, B35, and DR2 were significantly associated with ASD. Three significant predictors of an unfavorable outcome, either a chronic disease course or a longer time to clinical remission, were identified.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

In vitro effects of two gold compounds, and D-penicillamine on the production of interferon gamma.

There are contradictory reports on Interferon Gamma (IFN gamma) production by peripheral blood mononuclear cells (PBMC) in rheumatoid arthritis (RA). Since many patients previously studied were on Gold Sodium Thiomalate (GST), Auranofin (Auf), or D-Penicillamine (D-Pen) we have investigated the effects of these drugs on IFN gamma production using PBMC from normal controls (NC), and RA patients off GST, Auf, and D-Pen. Auf in low concentrations enhanced IFN gamma production by PBMC from NC but not RA; GST, and D-Pen had no effect. In other experiments PBMC were stimulated with concanavalin A (CONA A), or phytohemagglutinin (PHA). Auf, and GST inhibited IFN gamma production by CON A - stimulated NC and RA cells; D-Pen had no effect. Auf in low concentrations enhanced IFN gamma production by PHA - stimulated NC cells, but this effect was not seen with RA cells; GST inhibited both RA and NC cell production of IFN gamma, and D-Pen had no effect. Auf has a biphasic effect on IFN gamma production by NC cells with low concentrations being stimulatory or co-stimulatory, possibly by acting on T helper cells. Higher concentrations of Auf and GST, equivalent to those achieved in vivo in the course of therapy, inhibit IFN gamma production. These results suggest that gold therapy may affect IFN gamma production in RA, and could explain discrepancies noted in previous studies.

Adult↗
PubMed1990

Arthritis impact measurement scales: reliability of a French version and validity in adult Still's disease.

The Arthritis Impact Measurement Scales (AIMS) questionnaire was administered to 57 patients with adult Still's disease (ASD) and 104 controls. Six of the 9 scales were consistent for both groups (Cronbach's alpha greater than or equal to 0.70). Two scales, Mobility and Dexterity, were consistent for ASD only (alpha greater than or equal to 0.70). The reliability of a French version of the AIMS was similar to the standard AIMS. Of the 13 associations evaluating criterion related validity of the AIMS in ASD, 11 were statistically significant. We conclude that the French and standard AIMS are comparable and that this questionnaire is reliable and valid for assessing outcome in ASD.

Adolescent↗
PubMed1989

Improvements in pain responsiveness in patients with fibrositis after successful treatment with amitriptyline.

Thirty-six patients with fibrositis received low dose amitriptyline and placebo in a randomized double blind crossover study lasting 10 weeks. Amitriptyline was associated with significant changes on the outcome measures of pain, tender point sensitivity and patient assessment of well being. Clinically significant improvements for pain and tender point sensitivity and a statistically significant improvement in generalized pain responsiveness were found between patients who reported subjective improvement on amitriptyline and those who felt no change.

Adult↗
PubMed1988

Effects of D-penicillamine on mononuclear cells in vitro.

D-penicillamine (D-pen) inhibited pokeweed mitogen-induced plaque-forming cell (PFC) response in a dose-dependent manner. This inhibition was irreversible as preincubation for a few hours with the drug followed by washes still caused suppression of the PFC response. Pretreatment of the different mononuclear cell populations with D-pen for short periods (2-24 h) showed that both macrophages (Mo) and B lymphocytes were affected by the drug. By contrast T cells were resistant. Mo appears to be more susceptible to D-pen than B cells, and in the case of drug-treated Mo, the response was restored completely with the addition of 20% fresh Mo. Our results show that D-pen, without exogenous Cu2+, inhibits the polyclonal immunoglobulin secretion by human mononuclear cells in vitro due to a strong effect on both Mo and B cells. This may explain the decrease in serum immunoglobulin levels seen in patients with rheumatoid arthritis undergoing this therapy.

B-Lymphocytes↗
PubMed1988

Sodium aurothiomalate inhibits T cell responses to interleukin-2.

We studied the effects of the gold compound sodium aurothiomalate (SATM) on the responses of murine CTLL2 cells, and human T cells to Interleukin-2 (IL-2). SATM inhibited tritiated thymidine (3HTdR) incorporation by CTLL2 cells stimulated with human recombinant IL-2. Human T cells were cultured with phytohemagglutinin (PHA) in separate experiments and IL-2 receptor expression measured by using immunofluorescent anti-Tac serum; SATM inhibited IL-2 receptor expression. Furthermore, SATM when added concurrently with PHA, and IL-2 inhibited 3HTdR incorporation by human T cells in 5 day cultures. The kinetics of inhibition were further studied by adding PHA to T cells for 48 hours followed by the addition of SATM and IL-2; SATM inhibited 3HTdR incorporation even though receptor expression had occurred. These results suggest that SATM inhibits the stimulatory effects of IL-2 on T cells partly by interfering with IL-2 receptor expression, and partly by other mechanisms of action. These effects of SATM may explain some of the conflicting data in the literature on T cell responses to IL-2 in rheumatoid arthritis (RA), and suggest a possible mechanism of action for the drug in the treatment of RA.

Female↗
PubMed1988

Effects of sodium aurothiomalate on the polyclonal immunoglobulin secretion by human mononuclear cells in vitro.

Sodium aurothiomalate (GSTM) inhibited the pokeweed mitogen induced plaque forming cell (PFC) response in a dose dependent manner. This inhibition was irreversible as preincubation for 2 h with the drug followed by washes still caused a suppression of the PFC response. Pretreatment of the different mononuclear cell populations necessary for the PFC response with GSTM for short periods (2-24 h) showed that both macrophages (M phi) and B lymphocytes were inhibited by the drug but that T cells were resistant. In the case of GSTM treated M phi the response was restored partially with exogenous interleukin-1, and completely with the addition of 20% fresh M phi. Our results show that the inhibition of polyclonal immunoglobulin secretion by human mononuclear cells in vitro is due to an effect of GSTM on both M phi and B lymphocytes. This may explain the decrease in serum immunoglobulin levels seen in patients receiving chrysotherapy.

B-Lymphocytes↗
PubMed1988

Pure red cell aplasia in rheumatoid arthritis.

We report a patient with longstanding rheumatoid arthritis (RA) who developed pure red cell aplasia. This condition is a rare complication of RA. Our patient recovered, apparently in response to treatment with corticosteroids and cyclophosphamide followed by azathioprine.

Adrenal Cortex Hormones↗
PubMed1987

Comparison between sodium aurothiomalate and auranofin in rheumatoid arthritis. Results of a two-year open randomized study.

We compared the effectiveness of Auranofin, and sodium aurothiomalate (SATM) given for 2 years to patients with rheumatoid arthritis. This was an open trial with randomized entry to 2 treatment groups of 60 patients each. Only 40% of patients completed 2 years of treatment but these showed significant improvement in their indices of disease activity. Adverse reactions were a more common reason for withdrawal from SATM than from Auranofin, while insufficient therapeutic response was more common with Auranofin. This study also shows that inefficacy, toxicity, complicating illnesses, and lack of compliance limit the beneficial outcome of long-term chrysotherapy.

Adult↗
PubMed1987

Effects of gold on the production of and response to human interleukin-1.

We studied the effects in vitro of sodium aurothiomalate (GSTM) on the production of, and response to, a monocyte supernatant with interleukin-1 (IL-1)-like activity. Monocyte supernatant was produced by human peripheral blood monocytes stimulated with lipoprotein polysaccharide, and its IL-1-like activity assayed by its effect on tritiated thymidine incorporation by C3H/HeJ mouse thymocytes. GSTM inhibited the thymocyte response to monocyte supernatant even when added to monocyte supernatant and thymocytes after 48 h of culture. GSTM also inhibited production of IL-1-like activity by monocytes, when added to culture within the first 22 h. Inhibition of both response to and production of monocyte supernatant was dose dependent. These effects of GSTM on Il-1-like activity may constitute one of the mechanisms of action of the drug in rheumatoid arthritis.

Adult↗