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Biomedical subjects

K M Goebel

Publications and source records attributed to K M Goebel.

At least 19 recordsLinked to original sources
PubMed1990

A randomized controlled trial of ciamexon versus placebo in the immunomodulatory treatment of rheumatoid arthritis.

To determine the efficacy of the new immunosuppressive agent ciamexon in patients with rheumatoid arthritis (RA), we conducted a 6-month, prospective, double-blind, placebo-controlled study. The study included 21 outpatients with confirmed RA, who were randomized into 3 treatment groups of 7 patients each. Group 1 received 400 mg/day of ciamexon, group 2 received 100 mg/day of ciamexon, and group 3 received placebo. We investigated the influence of ciamexon on the clinical course, the systemic inflammatory activity, and the lymphocyte subsets in the peripheral blood. Significant, dose-dependent improvement was seen in both the clinical and the biochemical activity indexes at the end of the treatment period (P = 0.02 to P = 0.05). The proportion of activated T lymphocytes was significantly decreased (P = 0.05), and the proportion of CD8-positive lymphocytes was significantly increased (P = 0.03) in patients taking ciamexon. The major adverse effects were hepatotoxicity (2 patients) and rash (2 patients). This study documents the clinical efficacy of ciamexon therapy in RA patients and identifies the agent's potential toxicity.

Adjuvants, Immunologic↗
PubMed1989

[Immunomodulating basic therapy of rheumatoid arthritis using ciamexone].

Ciamexone, a 2-cyanoaziridine derivative, had been shown previously in animal studies to inhibit the proliferation of autoreactive lymphocytes dose dependently, without affecting the reaction against foreign antigens. To extend the experimental models of ciamexone's in vitro effects to the clinical level, we performed a pilot study to evaluate the clinical efficacy of ciamexone therapy. We further studied its influence on the systemic inflammatory activity and T-lymphocyte subsets in the peripheral blood of 10 patients with active rheumatoid arthritis (RA). Following 6 months' treatment with ciamexone all patients showed a significant decrease of both the clinical and biochemical scores. Concerning the T-lymphocyte subsets analysis, a relatively decreased rate of the activated T-lymphocytes was observed concurrently. Minor side effects included rash (n = 1), hepatotoxicity (n = 1) and diarrhea (n = 1). The study thus documents the clinical efficacy of ciamexone in patients with RA, but also indicates the agent's potential toxicity.

Adjuvants, Immunologic↗
PubMed1989

Correlation between synovial neopterin and inflammatory activity in rheumatoid arthritis.

According to recent investigations neopterin (a pyrazinopyrimidine derivative) is a biochemical marker that reflects the activity of the proinflammatory immunocellular system of the synovial tissue in rheumatoid arthritis (RA). Interferon gamma, derived from antigen activated T lymphocytes, stimulates macrophages to synthesise and release neopterin into the culture supernatant in vitro. To extend this in vitro model to a clinical level a sensitive new radioimmunoassay technique was used to measure neopterin concentrations in the synovial fluid (SF) of 17 patients with active RA, nine with osteoarthritis, and six with acute gout, and in that of 12 controls undergoing meniscectomy. The SF neopterin concentrations were significantly higher in patients with RA than in the other groups of patients, particularly the controls. Multivariant analysis showed that SF neopterin concentrations correspond better with the systemic inflammatory activity of RA than with the local disease activity of the knee joints. Thus the study strengthens the hypothesis that neopterin reflects the essential role of the activated immunocellular reaction in the pathogenesis of RA.

Adult↗
PubMed1988

Acquired transient autoimmune reactions in Lyme arthritis: correlation between rheumatoid factor and disease activity.

Lyme spirochaetal disease (LSD) is a complex multisystem disorder which has been recognized as a separate entity due to its close geographic clustering of affected patients. The study aimed at evaluating the clinical and immunological features of LSD with chronic symptoms of meningoradiculitis, carditis and pauciarticular arthritis. Six patients with LSD and erosive arthritis who developed an increase of serum IgM rheumatoid factor (RF) which correlated with the inflammatory activity of the disease are described in detail. Besides raised IgG antibody titers to Borrelia burgdorferi (B. burgd.) antigen measured by ELISA technique, circulating immune complexes, antinuclear antibodies (ANA) and RF measured by laser nephelometric immunoassay were detected. Increased ANA and RF antibody rates suggest that LSD may closely be linked with transient autoimmune phenomena. Thus, in some cases, B. burgd. antigens might be able to produce a strong polyclonal B-cell stimulation, hence leading to an unspecific autoimmune reaction. But the question remains if transient unspecific autoimmune reactions actually take part in the pathogenesis of LSD.

Adult↗
PubMed1987

Genetic aspects of sarcoidosis. Class II histocompatibility antigens and a family study.

In a study designed to evaluate the concept of inherited susceptibility to sarcoidosis, 73 patients with histologically proved chronic disease of sarcoid lung fibrosis (group 1) underwent typing of HLA-A, -B, -C and -DR antigens. Tests on 156 antiserum samples comprising 52 antigens of A, B, and C loci and on 35 comprising seven DR antigens on the surface of B cells were performed by means of the microdoplet assay of human serum cytotoxins. Two race-matched control groups consisted of 37 patients with lung fibrosis due to chronic extrinsic allergic alveolitis (group 2) and 162 healthy volunteers (group 3). The study further included a kinship with progressive sarcoidosis. The frequency of HLA-DR5 was significantly increased only in group 1 (relative risk, 6.6). HLA-DR5 was found in 38 patients (52%) in group 1, compared with five (14%) in group 2 and 23 (14%) in group 3. In the one family studied, HLA-DR5 was present only in one member, who had sarcoidosis. This study supports the hypothesis that the role of an infectious agent triggering sarcoidosis cannot be envisaged without considering genetically linked cofactors.

Adult↗
PubMed1987

Red cell metabolism and ferritin levels in iron deficiency anaemia.

Basic red cell ferritin (RCF) content reflects the rate of iron uptake by marrow erythroid cells in patients with anaemia due to chronic inflammation which are sometimes also associated with metabolic disorders of the erythrocytes. For 29 patients with active inflammatic states of chronic rheumatoid arthritis (RA) and microcytic (mean corpuscular volume up to 80fl) or normocytic (MCV 80-95fl) anaemia respectively, the mean RCF content, irrespective of plasma ferritin levels, was determined using a recently established ELISA test. Red cell intermediates (ATP, GSH, 2.3 DP.G) were measured using conventional methods. The results revealed decreased RCF levels (2.8 +/- 1.5 ag/RBC) in 12 patients with RA and normal values (8.8 +/- 4.7 ag/RBC) in 17 patients which obviously did not correlate with the degree of the anaemia. The extent and pattern of the intermediates of RBC did not significantly vary from normal values. Thus, ATP, GSH and 2.3 DPT levels of RBC were only slightly increased up to 10%, especially in those patients with higher anaemic degrees. The findings of our study suggest that conventional indices for iron metabolic disorder in anaemic patients with chronic inflammatic disease should include peripheral microcytosis, transferrin saturation, and RCF content but could neglect plasma ferritin concentrations. Concerning the RBC metabolism this study did not disclose any further influences on iron metabolism parameters due to changes of mean cell age in patients with RA. Specific alterations which might hence produce additional functional disturbances of the erythrocytes in the peripheral microcirculation thus leading further to tissue cell damages in RA could be excluded as well.

Adult↗
PubMed1987

Class II MHC antigen (HLA-DR3) predisposes to sarcoid arthritis.

Recent studies indicate that the susceptibility to various inflammatory rheumatic diseases is an inherited trait determined by gene products of the class II histocompatibility complex (HLA-DR determinants). In a study designed to evaluate the concept of inherited susceptibility to sarcoid arthritis (SA), 42 patients with histologically proved acute disease underwent typing of HLA-A, -B, -C and -DR antigens. Using the microdroplet assay of human serum cytotoxins, we employed 156 antiserums to identify 52 antigens on A, B and C loci and 35 to identify 7 DR antigens on the surface of B cells. An ethnically matched control group consisted of 134 healthy volunteers. The frequency of B cell isoantigen DR3 specificity was significantly increased in patients with SA (relative risk, 4.8); HLA-DR3 was found in 25 (60%) of the patients, compared with 31 (23%) of the controls. This study lends further support to the hypothesis that the putative role of an infectious agent triggering SA cannot be judged without considering genetic cofactors.

Adult↗
PubMed1986

[Genetic and diagnostic significance of the HLA picture in sarcoidosis].

67 patients with histologically proven sarcoidosis underwent typing of HLA-A, B, C and DR antigens to evaluate further the question of genetic susceptibility to the disease. A race-matched group of healthy volunteers (n = 42) served as controls. The frequency of the B-cell alloantigen specificity DR5 was significantly increased only in 49% of the patients with sarcoidosis compared to 21% of the race-matched control persons. This study supports the hypothesis that genetic factors may be associated with the etiopathogenesis of sarcoidosis. The result might serve also as an additional diagnostic pointer to the disease.

Adult↗
PubMed1986

[Lyme disease].

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed1985

[Long-term tolerance of oral gold therapy in rheumatoid arthritis. Frequency and intensity of undesirable side effects].

In view of encouraging results from various reliable multicenter studies, an interesting new oral agent, auranofin (triethylphosphine gold), is believed to be a major advance towards more effective treatment of rheumatoid arthritis with mild adverse reactions. The present study evaluates the long-term efficacy of auranofin in 46 patients with active rheumatoid arthritis and attempts to delineate further the results of drug monitoring concerning adverse reactions. Six patients withdrew due to untoward and partially serious events, e.g. thrombocytopenia, colitis or pancreatic disease. In view of the high frequency of side effects which required immediate withdrawal of auranofin in 13%, with a total of 37% of patients experiencing adverse reactions, it should be kept in mind that oral gold therapy may be a two-edged sword and requires further critical drug monitoring.

Administration, Oral↗
PubMed1984

[Effect of alcoholic hyperlipoproteinemias on the deformability and viscosity of erythrocytes].

This pilot study set out to evaluate the influence of the metabolic disorder due to acute alcohol toxicity on red blood cell (RBC) deformability. RBC deformability was measured optoelectronically by microcomputer-assisted polymicroviscometry (filtrometry). Chronic alcoholic patients (n = 12) with transient haemolytic anaemia, jaundice and hyperlipoproteinaemia were studied during the acute and the remittent phase of alcoholic disease. RBC obtained from patients in the acute phase revealed a markedly impaired deformability as compared with RBC suspensions studied when the alcoholic symptoms had subsided. The study lends further support to the hypothesis that predominantly during acute alcohol toxicity patients experience a marked impairment of the adhesive and rheological properties of RBC, which may finally impair the peripheral microcirculation of the whole blood.

Adult↗
PubMed1984

Different synovial fluid fibronectin levels in rheumatoid variants.

A circulating high-molecular-weight glycoprotein called fibronectin plays a part in cell adhesion and migration before phagocytosis and in morphology, differentiation, and metabolism in inflammatory synovial effusions of patients with rheumatic diseases. A technique of nephelometric immunoassay, based on the measurement of an antigen-antibody reaction, was applied to the analysis of fibronectin concentrations in synovial fluids from 20 patients with rheumatoid arthritis (RA) and other diseases (non-RA). RA synovial fluids have a significantly higher concentration than the specimens obtained from Yersinia arthritis patients (n = 12). The mean concentration of other synovial fluids, from 12 patients with osteoarthritis of the knees, did not significantly differ from the synovial fluids of control values obtained from patients who underwent meniscectomy. There was a considerably negative correlation between fibronectin levels and overall indices of inflammatory activity, such as Ritchie articular indices or a whole number of painful rheumatoid arthritis joints. However, a particularly distinct correlation was obtained when raised fibronectin levels were compared with the inflammatory activity of the knee joint, from which the specimen was aspirated. Thus, these findings suggest that the measurements of fibronectin in synovial fluid may be of some differential-diagnostic value in rheumatoid variants, but may only serve as an indicator of inflammatory activity if the joint, from which the specimen is obtained, is taken into account.

Adult↗
PubMed1983

[Pathologic fluidity, glycohemoglobin and erythrocyte metabolism disorder in Fontaine II diabetic macroangiopathy].

This pilot study set out to evaluate the influence of metabolic disorders due to diabetes mellitus on red blood cell (RBC) substrates, deformability and glycohaemoglobin (HbA1) levels. RBC deformability was measured optoelectronically by microcomputer-assisted polymicroviscometry (filtrometry) following separation of RBC into old (dense) and young (buoyant) fractions by means of density-layer centrifugation. 20 adult patients with type II diabetes mellitus associated with Fontaine II macroangiopathy underwent RBC investigations before and after diabetic therapy. Those RBC fractions containing older cells exhibited impaired metabolism, increased HbA1 levels and markedly altered deformability which significantly differed from values obtained from young RBC fractions. However, old RBC fractions only of patients treated for diabetes persistently displayed a slight increase in HbA1 levels associated with a still altered deformability, in contrast to the young RBC fractions which showed normal values again after diabetic treatment. The preliminary results suggest an adaptive alteration of RBC metabolism and function in diabetes, predominantly existing in old RBC, which still persists only in old RBC fractions after diabetic therapy. Thus, a prolonged pathologic effect of older RBC on the peripheral microcirculation may occur in diabetes, resulting in a further persistent maintenance of diabetic vascular disease.

Adult↗