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Biomedical subjects

M Harth

Publications and source records attributed to M Harth.

88 records · Page 5Linked to original sources
PubMed1979

Inhibition of lymphocyte responses by gold: modulation by time of drug addition and antigen dose.

Gold sodium thiomalate added to peripheral blood mononuclear (PBM) cell cultures inhibits the mixed leukocyte reaction (MLR), and cell-mediated cytotoxicity (CMC). The addition of GST to MLR was inhibitory only if the compound was added at the beginning of culture; late addition of GST did not inhibit MLR, or CMC. In a different set of experiments the number of stimulating cells added to MLR was varied. The inhibitory effects of GST decreased markedly as the number of stimulating cells added to culture was increased. The effects of gold in vivo may be modulated by a number of immunologically competent cells that are already antigenically stimulated, as well as by the amount of available stimulating antigen.

Antigens↗
PubMed1979

Inhibitory effects of gold and other drugs on mononuclear cell responses: a comparison.

The effects of gold sodium thiomalate (GST) were compared with those of acetylsalicylic acid (ASA), D-penicillamine (PEN), and methlyprednisolone succinate (MP) on the mixed leukocyte reaction (MLR), and on cell-mediated cytotoxicity (CMC) using mononuclear cells from normal human volunteers. GST and MP inhibited MLR in concentrations readily achieved in the serum, or tissues of patients. ASA showed only a modest effect on MLR, in high concentrations. All drugs inhibited CMC; PEN inhibited CMC at doses of 100 mcg/ml which were no inhibitory in MLR. ASA inhibited CMC at relatively low concentrations. The effects of some of the drugs on MLR and CMC were not consistent. This may be due to the preferential action of the drugs on various immunologically competent cells.

Aspirin↗
PubMed1979

Gold and modulation of the immune response.

The effects of gold on immune responses are reviewed. Gold salts used therapeutically can be followed by a decline in serum immunoglobulin levels, and rheumatoid factor titers in rheumatoid arthritis; in pemphigus there is similarly a drop in anti-epithelial antibody titers. Gold inhibits stimulation of immunoglobulin-secreting cells. Gold inhibits the activation of the classical and alternate complement pathways. Gold compounds inhibit numerous cell-mediated immune responses to various mitogens and antigens. Inhibition may be due to the effect of gold on macrophages acting as helper cell in these reactions. Auranofin is a new oral compound which seems to be particularly potent in its immuno-regulatory actions; it differs from other gold compounds in its pharmacokinetics, and in the nature of its ligand. Gold has also been reported to enhance certain immune reactions. The extent of the immuno-regulatory effects of gold in vivo is unknown, and the relation of these effects to its therapeutic actions remains to be clarified.

Animals↗
PubMed1978

Gold-induced thrombocytopenia.

Ten patients with rheumatoid arhritis treated with gold sodium thiomalate developed thrombocytopenia without bone marrow asplasia. There was no life-threatening blood loss, but petechiae, purpura, or echymoses were seen in eight patients. The serum gold levels monitored in one patient did not exceed levels seen in patients without thrombocytopenia. In three cases peripheral blood lymphocytes were cultured in the presence of gold and tritiated thymidine incorporation was significantly increased. Eight patients responded to steroid therapy, one patient to BAL and pencillamine, and one patient to vincristine.

Adrenocorticotropic Hormone↗
PubMed1977

Effects of a gold salt on lymphocyte responses.

The effects of sodium aurothiomalate (SATM) on certain lymphocyte functions in vitro were tested. Lymphocytes were obtained from both healthy donors and patients with rheumatoid arthritis (RA). SATM depressed tritiated thymidine uptake in lymphocyte cultures stimulated by phytohaemagglutinin, and in a mixed lymphocyte response assay. Cytotoxic effector cell generation assayed by percentage specific 51Cr release was also depressed by SATM using lymphocytes from healthy donors, and from patients with RA. These effects imply that SATM inhibits both exogenous thymidine uptake, and blastogenesis, and suggest that gold salts may act in RA by interference with T-cell dependent functions.

Arthritis, Rheumatoid↗
PubMed1976

The arthritic complaint in primary care: prevalence, related disability, and costs.

Surveys conducted in five areas of Southern Ontario obtained clinical and service utilization data from 5,478 adults over 25 years of age. The two week period prevalence rates of arthritic and rheumatic (AR) complaints were 1.72 per cent and 2.14 per cent among two groups of users of primary care. In free-living general populations, the rates ranged from 6.23 per cent to 8.84 per cent. It was shown that only 25 per cent of complainants with AR symptoms sought health services. Of all adults seen by family physicians in one year, 28 per cent presented at least once with an AR complaint. While 20 per cent of all respondents reported some physical impairment, 43 per cent of those with AR complaints had impairment. The excess impairment was two per cent. Complaints with AR symptoms used health services at costs 78 per cent higher than the average expenditures in the same communities. The essential role of the primary care practitioner in the identification and control of AR disorders is strongly supported.

Adult↗
PubMedDate not supplied

The modulation of interleukin 1 production by interferon gamma, and the inhibitory effects of gold compounds.

We have studied the in vitro effects of gold sodium thiomalate (GST) and auranofin (Auf) on the production of interleukin 1 (IL1) expressed as thymocyte co-stimulatory activity (TCSA), and interleukin 1 beta (IL1 beta) as modulated by interferon gamma (IFN gamma). Adherent cells (ADC), of which 80% were monocytes, were obtained from human peripheral blood, and stimulated with lipoprotein polysaccharide (LPS) for 24-48 h. TCSA and IL1 beta production by fresh ADC (0-24 h) was significantly higher than that of aged ADC (24-48 h). The addition of IFN gamma to ADC cultures, however, maintained the capacity of aging ADC to respond optimally to LPS. The addition of GST or Auf inhibited this modulatory effect of IFN gamma, resulting in a marked reduction of TCSA and IL1 beta production. The effects of IFN gamma on the production of IL1 may be important in the pathogenesis of rheumatoid arthritis (RA). The inhibition by GST and Auf of IFN gamma modulation may contribute to the therapeutic efficacy of these drugs in RA.

Auranofin↗
PubMedDate not supplied

Septic Discitis.

The clinical and laboratory findings in 15 patients with septic discitis are reported. The clinical picture was that of a sub-acute illness characterized by back pain, spinous process tenderness, and sciatic nerve root irritation. There was a considerable delay from clinical presentation to diagnosis (average 14 wk). The erythrocyte sedimentation rate was the most useful diagnostic laboratory blood test and the best indicator of disease activity. The relative value of plain radiographs, tomography, and radionuclide bone scans is discussed. Needle aspiration of the disc space was found to be a useful diagnostic test. We found that a diagnosis of septic discitis could be made even in the absence of positive bacterial cultures from various biologic fluids or from the disc space. Long-term oral and intravenous antibiotic therapy with controlled rest resulted in a favourable outcome.

Adolescent↗
PubMedDate not supplied

Gold therapy in rheumatoid arthritis. Interim report of the Canadian multicenter prospective trial comparing sodium aurothiomalate and auranofin.

One hundred and twelve patients with classical or definite rheumatoid arthritis (RA) were randomly assigned to receive either sodium aurothiomalate (GSTM) or auranofin (AF). Monthly clinical assessments (morning stiffness, grip strength, articular index, pain, quality of life) and concurrent hematological, biochemical, and urine studies were performed to monitor the efficacy/toxicity (E/T) ratio. Ninety-two patients have completed 3 months; 65, 6 months; 47, 9 months; and 30, 12 months. The groups were numerically balanced at each time period. Analysis of the 0-6 month period suggests that both drugs were equally and significantly beneficial after 3 months and that this was maintained at 6 months. Toxicity was as frequent in both groups but more serious in the GSTM group. The main side effects were gastrointestinal (diarrhea) in the AF group and mucocutaneous in the GSTM group. Half of the withdrawals (14 in each group) were because of side effects in the GSTM group and for inadequate therapeutic efficacy in the AF group. This study suggests that after 6 months of treatment the E/T ratio of AF is greater than or equal to that of GSTM. These conclusions will need to be confirmed during the ongoing longer observation period. A significant clinical difference between the 2 drugs is that in a given patient treated with GSTM, the onset of toxicity coincides with a good therapeutic effect. This relationship does not appear to exist during AF treatment.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Reticuloendothelial function in rheumatoid arthritis: correlation with disease activity and circulating immune complexes.

Fourteen patients with active rheumatoid arthritis had their reticuloendothelial function tested with clearance of heat damaged radiolabeled autologous erythrocytes. Only 3 of these 14 patients had prolonged red blood cell (RBC) clearance. No correlation was found between RBC clearance and level of circulating immune complexes, disease activity or disease duration.

Adult↗