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Biomedical subjects

A Dunky

Publications and source records attributed to A Dunky.

At least 37 records · Page 2Linked to original sources
PubMed1996

HLA-B27 determination using serological methods. A comparison of enzyme immunoassay and a microlymphocytotoxic test with flow cytometry and a molecular biological assay.

Typing for HLA-B27 is routinely performed in patients with seronegative spondarthritides. Besides the microlymphocytotoxic test (MLCT), other serological techniques have been developed such as enzyme immunoassays (EIA) using serum or plasma as a source for the determination of soluble HLA-B27 (sHLA-B27) and flow cytometric (FC) methods. The aim of the present study was to check the accuracy and reliability of the EIA for sHLA-B27 in comparison to the MLCT using antibodies against HLA-B27 and cross-reacting specificities (CRS), as well as an FC method and a molecular biological method. Any discrepant results should be typed with the MLCT using a complete panel of anti-HLA-class I antibodies, with FC and with a molecular biological technique. The EIA should also be repeated in those patients, using serum and plasma from a new venipuncture. In 81 patients with rheumatic disorders, the EIA and the MLCT using antibodies against HLA-B27 and CRS were performed. Based on the MLCT with a complete panel of anti-HLA-class I antibodies as a standard, discrepant test results were obtained for 9 out of 81 patients with the MLCT using antibodies against HLA-B27 and CRS and with the EIA. The following wrong results occurred: in the MLCT with anti-HLA-B27 and CRS, there were two false-negative results; in the EIA there were four false-negative and one false-positive results; one sample was undeterminable. In comparison with the MLCT, including the complete panel of HLA-class I antibodies, as well as with a molecular biological technique, typing with FC showed a complete concordance. Our investigations demonstrated that for routine typing for HLA-B27 the MLCT cannot be replaced by EIA because of a significant number of mistypings. The MLCT performed only with antibodies against HLA-B27 and CRS may also lead to typing errors. No errors were detected using flow cytometry. If only serological methods can be performed in a laboratory a combination of flow cytometry and MLCT could therefore enhance the safety of HLA-B27 typing.

Adult↗
PubMed1994

High free and latent collagenase activity in psoriatic arthritis synovial fluids.

Collagenase activity has been studied intensively in SF from OA and RA patients. Less is known about collagenolytic activity in PsA SF. Therefore we examined collagenolytic activity in crude and trypsin treated SF as well as the alpha 1-antitrypsin and alpha 2-macroglobulin concentrations in 50 patients suffering from OA (n = 13), RA (n = 17), and PsA (n = 20). Free collagenolytic activity was low in the crude OA SF (1.80 +/- 1.35 micrograms released collagen/min/ml SF) and almost equally low in RA SF (2.35 +/- 1.80 micrograms released collagen/min/ml SF; P > 0.3). The PsA SF, however, exhibited a significantly higher free collagenolytic activity (5.63 +/- 5.69 micrograms released collagen/min/ml SF; P < 0.05 in comparison to OA and RA SF). The treatment of the SF with trypsin further activated collagenolytic activity in each group (OA 2.17 +/- 1.35 micrograms released collagen/min/ml SF; RA 6.48 +/- 6.73 micrograms released collagen/min/ml SF; PsA 11.24 +/- 5.02 micrograms released collagen/min/ml SF) and yielded significant differences between OA and RA, OA and PsA, and RA and PsA SF (P < 0.05). Concomitantly with the collagenolytic activity, the alpha 1-antitrypsin and alpha 2-macroglobulin concentrations of the SF were measured. In SF from patients with PsA (172.9 +/- 69.4 mg/100 ml) and RA (190.6 +/- 64.7 mg/100 ml) the alpha 1-antitrypsin was significantly higher than in those from OA SF (106.1 +/- 39.2 mg/100 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Inhibition of complement activation in aged individuals due to increased plasma fibronectin concentration.

The influence of fibronectin levels on complement activation by immune complexes and non-immune activators in elderly humans was investigated. The present study demonstrates for the first time a shift in complement activation from the classical to the alternative pathway, if the fibronectin concentration rises above a certain level (near 1 mg/ml). Plasma of elderly individuals often contains large amounts of fibronectin, the reason for which is unknown. While C1 consumption is inhibited under these conditions, C3 depletion remains largely unaffected. This could be due to a compensatory triggering of the alternative reaction sequence caused by fibronectin deposition at and blockade of C1-activating sites. Probable physiologic implications of this changed complement activation pattern are discussed.

Adult↗
PubMed1989

Methotrexate serum-level determinations during low-dose therapy of rheumatoid and psoriatic arthritis.

In 29 patients, 21 suffering from psoriatic arthritis and eight patients suffering from rheumatoid arthritis, methotrexate serum-levels were determined by means of radioimmunoassay. The aim of the investigation was to recognize an eventual dependence of the serum level of methotrexate on the total cumulative dose and to test the possibility of a concomitant therapy control. Beside the determinations of the serum levels of methotrexate, clinical examinations and laboratory tests were done at regular intervals. The values obtained showed no significant increase during the course of therapy compared to the values at the beginning of the treatment. Likewise no correlation to the total cumulative dose, the clinical picture or to the occurrence of side-effects could be found. Nor could any relationship between the changing of laboratory parameters and the methotrexate serum-levels be observed. No differences appeared in the methotrexate serum-levels during therapy of either rheumatoid or psoriatic arthritis patients. In conclusion it seems impossible to monitor a low-dose methotrexate therapy by continuous determinations of the serum levels of the drug.

Arthritis, Rheumatoid↗
PubMed1988

Transsynovial kinetics of piroxicam in patients with rheumatoid arthritis.

Twenty-four patients suffering from rheumatoid arthritis, who required articular puncture, participated in this open label study. Following a washout period of 7 days piroxicam 20 mg was administered once daily for 7 days. The average drug concentration in a dose interval in plasma fluctuated between 4.45 micrograms/ml and 8.02 micrograms/ml, and in synovial fluid it ranged between 4.16 micrograms/ml and 5.55 micrograms/ml. Piroxicam was eliminated from plasma with a half-life of 41.7 h and 43.2 h from synovial fluid as calculated from measured and interpolated data from all patients. Despite the short treatment period, clinical improvement could clearly be demonstrated.

Adult↗
PubMed1988

Autoimmunity and T-cell subpopulations in old age.

To investigate the interrelationship between T-cell-dependent immune functions and autoimmune phenomena in old age we determined T-cell subpopulations in 20 aged healthy individuals (80-96 years old) using monoclonal antibodies. These persons were also investigated as to humoral parameters such as antinuclear antibodies, rheumatoid factors (IgG-, IgA-, IgM-RF), antibodies to collagen types I-IV as well as autoantibodies to organ-specific antigens. In addition, immune complexes were determined. We found that aged individuals have an increased frequency of autoantibodies as compared to a young control population, each aged subject presenting with at least one autoantibody species. Immune complexes, however, were only rarely detected. Three individuals showed a slightly increased T-helper/T-suppressor cell ratio, four had a decreased ratio. An increased number of T-suppressor cells was significantly correlated with a lowered incidence of anticollagen antibodies. Other parameters tested by us: fibronectin, laminin, procollagen type III, C3 and C4 complement components, immunoglobulins and acid alpha 1-glycoprotein. Aged individuals have significantly higher serum levels of fibronectin, while laminin and procollagen concentrations are in the normal range. A large percentage of old individuals had increased serum levels of C3 and/or C4. The acute phase protein orosomucoid, however, was in the normal range.

Adult↗
PubMed1988

Pharmacokinetics of intravenous and oral enoxacin in healthy volunteers.

In a randomized, crossover study single 200 and 800 mg doses of enoxacin were administered intravenously and orally to eight healthy normal volunteers. Plasma and urinary enoxacin concentrations and urinary concentrations of its oxo-metabolite were determined by high-performance liquid chromatography. At the end of a 1 h intravenous infusion period, mean enoxacin plasma concentrations were 1.8 and 6.6 mg/l for the 200 and 800 mg doses, respectively. Disappearance of enoxacin from the systemic circulation appeared to follow first order kinetics with harmonic mean elimination half lives of 3.3 and 4.7 h for the 200 and 800 mg dose groups, respectively. However, enoxacin kinetics were dose-dependent over the dose range tested. Total body clearance decreased and elimination half-life increased with increasing dose. The volume of distribution was large (2.8 l/kg) and independent of dose. Absorption of orally administered enoxacin was rapid, with mean peak plasma concentrations (1.0 and 3.8 mg/l) appearing one to two hours postdose. Absolute oral bioavailability averaged 89%, and was independent of the dose administered. Cumulative enoxacin urinary recovery accounted for 51-53% of the dose irrespective of dose or route of administration. Enoxacin renal clearance exceeded creatinine clearance indicating that urinary excretion of enoxacin involved both glomerular filtration and tubular secretion. Urinary excretion of the oxo-metabolite averaged 16% and 11% following the 200 and 800 mg dose, respectively. Evidence of dose dependent decrease in enoxacin renal clearance and formation of its oxo-metabolite was observed. Enoxacin was well tolerated during the course of the trial. The present study shows that enoxacin pharmacokinetics can be characterized by apparent first order elimination, large volume of distribution, and dose-dependent increase of half life. Oral absorption of enoxacin is complete over a wide dose range.

Administration, Oral↗
PubMed1988

The influence of synovial fluids from patients with rheumatic diseases on chick embryo fibroblasts.

Primary chick-embryo fibroblasts (PCEF) were used as target cells to measure the influence of synovial fluids of patients suffering from osteoarthritis (OA; n = 5), rheumatoid arthritis (RA; n = 12) and psoriatic arthritis (PA; n = 2). The following metabolic cell products were measured: DNA, RNA, glycosaminoglycans (GAG), sulfated glycosaminoglycans, protein and collagen, with the same joint effusions being used in each test. Since it is not a single substance that provokes a stimulating or inhibiting effect in the joint, the crude synovial fluids were applied in these preliminary experiments. It was found that each type of synovial fluid showed an influence on the biological processes in the PCEF. The DNA, RNA and GAG syntheses were strongly influenced by the joint effusions, in contrast to the protein, collagen and sulfated glycosaminoglycan syntheses which were less affected. Generally, the nucleic acid synthesis differed significantly between the OA, RA and PA synovial fluids. The addition of heparin to the synovial fluids caused an additive inhibiting effect on the DNA synthesis but did not influence the other biochemical parameters. The synovial fluids of RA patients, and to a much greater extent those of PA patients, inhibited the thymidine incorporation whereas OA synovial fluids had a less pronounced effect. This result indicates a disease-dependent composition of the synovial fluids. RNA synthesis was diminished in all three groups, but again this effect was strongest in the case of the PA synovial fluids. GAG synthesis was markedly stimulated by the PA synovial fluids and somewhat, though to a lesser extent, by the OA and RA synovial fluids. The sulfated glycosaminoglycan synthesis in the PCEF, as revealed by 35S incorporation into the GAG, was less influenced and on the whole stimulated by the OA and RA synovial fluids. The same trend could be observed with regard to the collagen synthesis. The intracellular protein synthesis was less influenced by the OA (91.9%) and more strongly suppressed by the RA (78.7%) and the PA (76.7%) synovial fluids. PCEF therefore appear to be a convenient and sensitive target cell system to study alterations of biochemical processes caused by crude synovial fluids and also of different origin by individual factors isolated from synovial fluids.

Animals↗
PubMed1988

[Blood cell concentration of methotrexate in long-term therapy of inflammatory rheumatic diseases].

To verify the possibility of a concomitant therapy control in 31 patients (18 psoriatic arthritis [PA], 13 rheumatoid arthritis [RA]) the blood cell concentration of Methotrexate (MTX) was continuously measured over a period of 6 months. The determinations were carried out by using a RIA of the CIS Corp. At any time MTX was determined laboratory and clinical examinations were done and the P-III-P serum-level was measured by using a RIA of the Behringwerke. The cellular MTX showed to be statistically significantly elevated compared to baseline, whereas within ranges of total cumulative dosages only insignificant fluctuations could be noticed. Like in the treatment of Psoriasis a strict correlation between the weekly administered dose and the cellular MTX could be established, the total cumulative dose, however, had no influence on the cellular MTX-level. In the treatment of RA slightly higher weekly dosages were necessary, which caused significantly higher cellular MTX concentrations in RA patients. Some correlations between clinical as well as serological parameters of disease activity could be noticed, nevertheless they do not allow distinct interpretations. In both diseases a significant relationship between the cellular MTX-level and the P-III-P serum-level could be realized. A storage of MTX in blood cells, especially in erythrocytes, seems to be evident. To reach therapeutical benefit in RA slightly higher mean dosages may be necessary. A therapy monitoring by the means of continuous determinations of cellular MTX seems to be impossible. In contrast an approach to the early detection of liver fibrosis can be given by the correlation between cellular MTX and the P-III-P serum levels.

Adult↗
PubMed1987

Effects of pirazolac on arachidonic acid metabolism in the human synovial system.

Six patients suffering from rheumatoid arthritis with massive knee joint effusions were treated with single daily doses of 600 mg pirazolac, a novel non-steroidal anti-inflammatory drug, for 3 days. Before the first dose, 3 hours after the second and the third dose, specimens of plasma and synovial fluid were drawn simultaneously. Plasma and synovial fluid concentrations of pirazolac, as determined by HPLC, amounted to 47.9 micrograms/ml and 19.8 micrograms/ml (Day 2) and 55.5 micrograms/ml and 18.7 micrograms/ml (Day 3), respectively. The samples were analyzed for PGE2, LTB4, LTC4 and LTD4 applying various extraction procedures and subsequent radioimmunoassays. PGE2 levels decreased during treatment from 928 pg/ml to 443 pg/ml after the third dose of pirazolac. LTB4 levels were slightly but insignificantly augmented. LTC4 and LTD4 concentrations were below the detection limit prior to and after administration of the drug.

Aged↗
PubMed1986

Alpha 2-macroglobulin-proteinase complexes as correlated with alpha 1-proteinase inhibitor-elastase complexes in synovial fluids of rheumatoid arthritis patients.

The levels of alpha1-proteinase inhibitor-elastase and alpha 2-macroglobulin (alpha 2M)-proteinase complexes were measured in synovial fluids from arthritis patients by use of specific immunosorbent assays. Both types of proteinase inhibitor-proteinase complexes were significantly correlated with each other as well as with the total neutrophil count in synovial fluids of rheumatoid arthritis patients but were discordant in synovial fluids of patients with osteoarthritis. One synovial fluid sample showed active (inhibitory) alpha 2M as well as active collagenase. We purified alpha 2M from pooled synovial fluids obtained from patients with rheumatoid arthritis. This alpha 2M retained approximately 90% of its proteinase binding (inhibiting) capacity, compared with that of normal plasma alpha 2M. We found no evidence that alpha 2M was inactivated by means other than proteinases.

Arthritis, Rheumatoid↗
PubMed1986

Transsynovial distribution and protein binding of pirazolac in patients with rheumatoid arthritis.

Following a washout period of 7 days, twenty-one patients suffering from rheumatoid arthritis and 3 from osteo-arthritis, who all required articular puncture were given a non-steroidal anti-inflammatory drug pirazolac 450 mg b.d. for 7 days. After discontinuation of the treatment the subjects were divided into 4 groups each of 6 patients. The non protein bound fraction of pirazolac in synovial fluid (0.86%) was significantly higher than that in plasma (0.53%). The average pirazolac concentration in plasma within the dosing interval fluctuated between 30.9 micrograms/ml and 59 micrograms/ml, and in synovial fluid between 16.6 micrograms/ml and 29.9 micrograms/ml. The half-life of pirazolac calculated from the measured and interpolated data from all patients was 30.9 h in plasma and 66.2 h in synovial fluid. The absolute free concentrations in plasma and synovial fluid (approx. 250 ng/ml) were in the range of the IC50-values for inhibition of cyclooxygenase in mouse peritoneal macrophages.

Adult↗
PubMed1984

The clinical pharmacokinetics and tolerance of enoxacin in healthy volunteers.

In a single-dose tolerance and pharmacokinetics study, enoxacin doses ranging from 200 to 1600 mg were administered orally to 12 healthy normal volunteers. Plasma assays demonstrated rapid absorption of enoxacin with first-order elimination and a half-life averaging 3.4-6.4 h. Renal clearance accounted for approximately 40% of total body clearance of drug. In a second placebo-controlled study, 18 normal volunteers received enoxacin in doses of 400, 600 or 800 mg twice daily for 14 days. Plasma concentrations and pharmacokinetic parameters obtained after the first dose were not significantly different from those observed in the single-dose study. With repeated administration, steady-state plasma concentrations were achieved in three days or less. Steady-state pharmacokinetics were characterized by prompt absorption, first-order elimination, and high urinary concentrations of enoxacin. The most frequently-reported adverse experiences involved the gastro-intestinal tract, the central nervous system, and the skin.

Clinical Trials as Topic↗
PubMed1983

[Use of the proteinase inhibitor alpha 2-macroglobulin in synovial fluids of arthritis of different origins and its relation to serologic parameters].

Collagen and proteoglycan are major constituents of the articular cartilage. In rheumatic disorders joint damage is attributed to the excessive action of proteoglycan degrading proteinases (P) and specific collagenases, which are released by connective tissue- and inflammatory cells in the synovial compartment. Collagenase is secreted in a latent form, which requires activation by a variety of serine-proteinases. Thus, several different proteinases are involved in pathogenesis of joint disease. alpha 2-macroglobulin was shown to be the major inhibitor of proteinases in complex biological fluids. To assess the utilization of alpha 2M by proteinases in synovial fluids (SF) from different arthritides we have employed a newly introduced solid phase immuno-sorbent assay, which allows concentration of alpha 2M and its proteinase-complexes from biological fluids. Most pronounced utilization of alpha 2M (up to 50% of total SF alpha 2M) was found in marked joint inflammation as judged from RF, immunocomplexes, C3 complement activation and acute phase reactants. Supported by animal experiments, which revealed that alpha 2M.P complexes but not native alpha 2M induce synovitis in rabbits after repeated intra-articular administration, it is suggested that pathophysiological rise of alpha 2M.P may impair cellular functions in inflammatory connective tissue, e.g. synovial tissue.

Antigen-Antibody Complex↗
PubMed1983

[Oligoarthritic joint symptoms of the hands in metastasizing bronchial carcinoma].

Bronchial carcinomata very frequently metastasize to bony tissue. The most common sites are generally known, but metastases can also occur in atypical locations where they then simulate other clinical syndromes. The present paper describes the clinical picture of a patient with small-cell bronchial carcinoma metastasizing to the finger joints. The frequency of this manifestation is investigated on the basis of the literature.

Aged↗
PubMed1983

[Cellular and humoral immune phenomena in psoriatic arthritis].

The function of cellular immunity factors (lymphocyte transformation and phagocytosis by polymorphonuclear leucocytes [PMN] and monocytes in connection with the concentration of intracellular ATP) and humoral immunity factors (serum concentration of immunoglobulin and complement factors C'3 and C'4) was investigated in 16 controls, 21 patients with psoriatic arthritis and 19 with psoriasis vulgaris. The results were compared with the clinical and anamnestic data of the patients. PMN phagocytosis of zymosan opsonized with rabbit standard serum was decreased in psoriasis vulgaris in comparison with the controls. Also, monocyte phagocytosis of non-opsonized zymosan was decreased in psoriatic arthritis, as compared with psoriasis vulgaris. Furthermore, in PMNs intracellular ATP was elevated in psoriatic arthritis as compared with the controls, but decreased in comparison with patients with psoriasis vulgaris. The intracellular ATP in monocytes was decreased in psoriasis vulgaris as compared with the controls. Humoral immunological findings: serum IgG concentration was higher in psoriatic arthritis than in controls and in psoriasis vulgaris. Elevated C'3 and decreased C'4 serum concentrations in psoriatic arthritis indicate an activation of the complement system.

Adenosine Triphosphate↗