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Biomedical subjects

H Menninger

Publications and source records attributed to H Menninger.

At least 19 recordsLinked to original sources
PubMed1998

[Basic therapeutic combination therapy in chronic polyarthritis: an overview].

Therapy of rheumatoid arthritis with a combination of several disease-modifying drugs aims towards better control of the disease than achievable by monotherapy. Based on a broad variety of clinical studies, revealing more or less positive results, several combinations have been suggested: the inclusion of cyclosporin into combinations with methotrexate, the inclusion of sulfasalazine into combinations with methotrexate, the combined use of two chemotherapeutic substances, including methotrexate, azathioprine and cyclophosphamide, the inclusion of chloroquine derivatives into such or other combinations, and the combination of methotrexate with injectable gold. The validity of some of the studies is affected by high drop out rates and by the unknown influence of concomitant therapy with corticosteroids. Our own beneficial experience with the triple combination of methotrexate with azathioprine and chloroquine in 21 patients with refractory rheumatoid arthritis is summarized.

Antirheumatic Agents↗
PubMed1998

Other pain syndromes to be differentiated from fibromyalgia.

Several common chronic pain syndromes come to the attention of the rheumatologist demanding for differentiation from fibromyalgia (FM), although they are often associated with it. They may mimic FM by (1) the occurrence of wide spread pain, (2) the chronicity of complaints, (3) the preponderance of females in some of these, and (4) the lack of objective data to be derived from imaging techniques and laboratory tests. Pain is produced by the disturbance of normal function ("dysfunctional syndromes", MASI, ref. 6). Recognition requires examination of the locomotor system under biomechanical auspices both at rest and during movement in order to diagnose hyper- and hypomobility syndromes; treatment of these conditions is guided by principles to improve biomechanical function. In addition, the skin needs to be examined to detect panniculosis (also called "cellulitis"), which may be mixed up with FM due to its preferential occurrence in peri- or postmenopausal women. It is concluded that the aforementioned differential diagnosis needs to be considered appropriately in coinciding FM and all studies dealing with FM.

Chronic Disease↗
PubMed1998

A 36 month comparative trial of methotrexate and gold sodium thiomalate in the treatment of early active and erosive rheumatoid arthritis.

OBJECTIVE: To compare the safety and efficacy of methotrexate (MTX) and gold sodium thiomalate (GSTM) in patients with active early erosive rheumatoid arthritis (RA) during 3 yr. METHODS: A total of 174 patients from two centres were randomly assigned to receive weekly i.m. injections of either 15 mg MTX or 50 mg GSTM for 1 yr in a double-blind fashion. Thereafter, the study was continued as an open prospective trial for an additional 2 yr with the same dose of MTX and half of the GSTM dose. Clinical and laboratory evaluations were carried out at baseline and at months 6, 12, 18, 24 and 36 in all patients, including withdrawals. RESULTS: An intention-to-treat analysis revealed inactivation ['clinical remission': no swollen/tender joints, erythrocyte sedimentation rate (ESR) of < 20 mm/h in males and < 30 mm in females, no corticosteroids within the last 4 weeks] in 33.3% of MTX patients and 37.9% of GSTM patients. The mean time to inactivation was insignificantly shorter with GSTM (MTX: 12.1 months; GSTM: 9.1 months; P = 0.06). At least marked improvement (> 50% reduction of the number of swollen/tender joints and of the ESR) was found in 78.2% (MTX) and 87.4% (GSTM). Withdrawal from the study due to toxicity was recorded in 16.1% of MTX and 52.9% of GSTM patients after a mean time of 30.6 and 6.1 months, respectively (P = 0.0001). In MTX and GSTM non-completers, inactivation was recorded in 24.2 and 54.7% of all patients. Among completers (54 and 34 patients, respectively), significant improvement compared to baseline was noted in all seven clinical variables (morning stiffness, overall joint pain, count of tender/swollen joints, Lansbury articular score, functional score and grip strength), ESR and C-reactive protein without significant intergroup differences. The steroid-sparing effect appeared more pronounced with GSTM. CONCLUSION: Over 36 months, treatment with MTX or GSTM induces inactivation ('clinical remission') of early and erosive RA in about one-third and at least marked improvement in four-fifths of patients (intention-to-treat analysis). Patients withdrawn from MTX or GSTM due to toxicity develop a clinical remission from the disease; this occurred more often with GSTM. Tolerability is significantly better with MTX.

Adolescent↗
PubMed1998

Progression in early erosive rheumatoid arthritis: 12 month results from a randomized controlled trial comparing methotrexate and gold sodium thiomalate.

OBJECTIVE: To compare radiographic outcomes in patients with active early erosive rheumatoid arthritis (RA) who were treated with methotrexate (MTX) and gold sodium thiomalate (GSTM). METHODS: A total of 174 patients from two centres were randomly assigned to receive weekly i.m. injections for 12 months of either 15 mg MTX or 50 mg GSTM in a double-blind fashion. Radiographic evaluations including standardized scoring of 38 joints of the hands, wrists and forefeet, and count of eroded joints, were carried out at baseline and after 6 and 12 months in all patients, including withdrawals. RESULTS: An intention-to-treat analysis revealed no statistically significant difference in the progression of radiographic scores between treatment groups after 6 months (3.4 with MTX vs 2.6 with GSTM, P = 0.66) and after 12 months (6.0 vs 4.8, P = 0.44). A similar pattern was observed for the number of joints with erosions. The slope of radiographic progression was significantly reduced in the second half-year compared to the first 6 months in both groups. Erythrocyte sedimentation rate and C-reactive protein at baseline, and the presence of rheumatoid factor (RF), were the main predictors of progression in bivariate analysis. RF remained as the only predictor for radiographic outcome in multivariable analysis. CONCLUSION: In parallel to clinical improvement, both GSTM and MTX reduce the slope of radiographic progression in patients with active erosive RA.

Aged↗
PubMed1997

Decrease of interleukin 6 during the first 12 months is a prognostic marker for clinical outcome during 36 months treatment with disease-modifying anti-rheumatic drugs.

The aim of this study was to determine prognostic markers for the outcome after 36 months of therapy with disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) and to study serial cytokine serum levels. During 36 months, 20 patients receiving DMARDs (nine patients gold sodium thiomalate and 11 patients methotrexate, no comparison undertaken) were followed for clinical and laboratory data. Investigation at baseline, 12, 24 and 36 months, included clinical, radiological and laboratory parameters such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and interleukin (IL)-1 beta, IL-6, tumor necrosis factor alpha (TNF-alpha), IL-1 receptor antagonist (IL-1RA) and IL-2. During the 3 yr of therapy, the patients showed significant clinical improvement and decline of ESR, CRP, and serum levels of IL-6 and IL-2. The decrease in IL-6 serum levels during the first year of therapy correlated significantly with the decrease, after 36 months, in the number of inflamed joints (r = 0.7608, P < 0.005), Lansbury index (r = 0.6642, P < 0.005) and morning stiffness (r = -0.6561, P < 0.005). In contrast to IL-6 or IL-2, TNF-alpha and IL-1RA did not vary significantly during the 3 yr of therapy. During 36 months of therapy, patients treated with DMARD showed significant improvement of clinical parameters and a trend for delayed progression of radiographic damage. The decrease in IL-6 concentration in serum during the first 12 months was the best prognostic marker for the clinical outcome after 36 months of DMARD therapy.

Aged↗
PubMed1997

Comparison of intramuscular methotrexate and gold sodium thiomalate in the treatment of early erosive rheumatoid arthritis: 12 month data of a double-blind parallel study of 174 patients.

The objective was to compare the safety and efficacy of methotrexate (MTX) and gold sodium thiomalate (GSTM) in patients with early erosive rheumatoid arthritis (RA). A total of 174 patients with active early erosive RA without deformities were enrolled in a 12 month, two-centre double-blind randomized trial. They received a weekly i.m. dose of 15 mg MTX (n = 87) or 50 mg GSTM (n = 87), respectively. Clinical and laboratory evaluations were carried out every 3 months in all patients, including the withdrawals. Ten patients (11.5%) in the MTX group and 21 patients (24.1%) in the GSTM group achieved a clinical remission of the disease [no swollen joints, erythrocyte sedimentation rate (ESR) < 20 mm, no steroids] within the study period (P < 0.05). An at least marked improvement (> 50% reduction of the number of swollen and tender joints and the ESR) was assessed in 59/87 (68%) and 66/87 (76%) patients treated with MTX or GSTM, respectively (P > 0.05). Significantly more patients in the GSTM group were withdrawn due to toxicity (six MTX/32 GSTM). A total of 126 patients (73 on MTX and 53 on GSTM) completed 12 months on their original medication. In the completers, a significant improvement of > 50% compared to baseline was noted in all six clinical variables [morning stiffness, joint count of swollen and tender joints, Lansbury index, grip strength and activities of daily living (ADL) score], the ESR and the C-reactive protein, without intergroup differences. The number of patients taking prednisone was reduced from 21 to 7% in the MTX group and from 15 to 4% in the GSTM group. While significantly more patients achieved a clinical remission with GSTM treatment, tolerability was significantly better with MTX.

Antirheumatic Agents↗
PubMed1995

Immunoprinting: various genes are associated with increased risk to develop rheumatoid arthritis in different groups of adult patients.

To identify genes that contribute to the manifestation of rheumatoid arthritis we performed association studies via microsatellite analyses of immunorelevant loci (HLA-DRB, 5 T cell receptor loci, TNFa IL1, IL2, IL5R and CD40L). A total of 183 patients and 275 healthy controls were typed in terms of HLA and grouped according to the known predisposing HLA-DRB1 genes (DRB1*04; relative risk approx. 5; DRB1*01, relative risk approx. 2; a third group carried neither allele). Microsatellite polymorphisms characterizing the TCRBV6S3, CD3D, IL1A, IL2, and IL5R genes did not show significant associations with rheumatoid arthritis, whereas TCRBV6S1, TCRBV6S7, TNFa, and CD40L genes may influence relative protection or risk in certain groups of patients. Analysis of a microsatellite marker adjacent to the transcription element alpha (TEA) in the T cell receptor alpha delta complex indicates that in the cohort carrying neither the DRB1*04 nor the DRB1*01 allele the relative risk to acquire rheumatoid arthritis is increased (> 13) or decreased (< 0.07), depending on the inherited microsatellite allele adjacent to the TEA locus. Sequence analysis of the closely linked TEA region from patients and controls revealed a novel dimorphism. Only the newly identified TEA allele leads to binding of a nuclear protein that may be involved in the regulated expression of the TCRDA genes. Subsequent typing of rheumatoid arthritis patients and controls revealed, however, that the association of the microsatellite marker is largely independent of the TEA allele, confirming incomplete linkage in the 2 kb region of the TCRDA locus. These results are discussed in the context of hot spots of recombination in this genomic region and other linked candidate sequences that predispose to develop rheumatoid arthritis.

Alleles↗
PubMed1995

Progression and repair in radiographs of hands and forefeet in early rheumatoid arthritis.

OBJECTIVE: To evaluate radiographs of patients with early rheumatoid arthritis (RA) for progression and repair. METHODS: Radiographs of hands and forefeet over 3 years were evaluated at 34 joints based on the modified Larsen-index, the number of joints with erosions, the area of osseous defects including erosions and cysts, the radiologic activity of lesions and--in relation to preceding status--the number of joints with qualitative radiologic improvement or deterioration, respectively, not necessarily seen by the other methods. RESULTS: Counting of joints with erosions and assessment of the area of osseous defects yielded the most impressive results for disease progression with the number of eroded joints being the simplest method. Reparative phenomena included recortication, "filling in" and diminution in size of erosions and paraarticular cysts, newly developing demarcation of a previously indistinct articular outline, and the increase in trabecular structure in the vicinity of erosions. The evaluation of qualitative changes showed reparative phenomena with increasing frequency involving up to 9.3% of the joints during the 3rd year, compared with 7.1% of the deteriorating joints. CONCLUSION: Progression in early RA can be quantitated easily by counting joint erosions. This method appears to be more sensitive than Larsen's approach. Repair can be shown early in the course of the disease (as early as the second 6-month observation period) by assessing both radiologic activity and qualitative changes, which are not necessarily apparent in the foregoing quantitative methods. Reparative phenomena associated with healing of erosions and cysts can be noted increasingly during continuous longterm observation. Evaluation for healing phenomena should be standardized and considered for inclusion in therapeutic trials of RA.

Arthritis, Rheumatoid↗
PubMed1994

Intra-articular treatment of rheumatoid knee-joint effusion with triamcinolone hexacetonide versus sodium morrhuate. A prospective study.

Thirty-one patients with knee effusions associated with rheumatoid arthritis (RA) have been treated with two intraarticular (i.a.) injections of each 330 mg sodium morrhuate (SM) used for synoviorthesis versus a single injection of 20 mg triamcinolone hexacetonide (TA). During an observation period of one year, five articular parameters as well as patient's and doctor's global assessments were evaluated. TA showed an earlier onset and a longer duration of therapeutic effects with high statistical significance. The maximum improvement was significantly more pronounced with TA than with SM. Finally after one year improvement measured by a remission index was observed in 81% versus 33% resp. of all joints injected. Due to ineffectiveness of the primary treatment nine patients (60%) out of the SM group, but not patient out of the TA group had to be crossed over to the other treatment. SM usually caused a reactive effusion within hours after injection requiring arthrocentesis. In conclusion efficacy and tolerability are clearly better for TA than for SM.

Adult↗
PubMed1994

The efficacy and relative bioavailability of diclofenac resinate in rheumatoid arthritis patients.

The pharmacodynamics and pharmacokinetics of 75 mg resin-bound diclofenac (resinate) were compared with enteric-coated tablets containing 75 mg of diclofenac in a double-blind randomized crossover trial in 16 patients suffering from rheumatoid arthritis. Diclofenac was significantly faster absorbed from the resinate than from the enteric coated formulation (tlag = 0.454 h vs. 0.998 h, tmax = 1.41 h vs. 2.56 h) and reached lower peak concentrations (Cmax = 1.64 micrograms/ml vs. 2.59 micrograms/ml). No significant differences were found concerning the area under the plasma level-time curves and the mean residence times. Smaller variances were found for the tmax and the mean residence times in the group treated with diclofenac resinate. Onset and duration of analgesia, as assessed by visual analogue scales were similar in both treatment groups, but did not correlate with the plasma concentrations. Four patients experienced adverse effects including gastric pain, transaminase increases, proteinuria and plasma creatinin increase. No uncommon adverse effects were observed with the new preparation.

Absorption↗
PubMed1992

Oligoclonal T cells in rheumatoid arthritis: identification strategy and molecular characterization of a clonal T-cell receptor.

Immunodominant antigens in rheumatoid arthritis (RA) should induce an expansion of T cells bearing a corresponding T-cell receptor (TCR). We therefore analysed the TCR repertoire at the site of inflammation using two fundamentally different strategies. The total TCR repertoire was examined by generating 'representative' T-cell clone panels, which were subsequently tested for clonality by restriction mapping of the TCR beta gene locus. No clonality was detected in large T-cell clone panels generated with cells from three patients. However, when we selectively analysed the TCR repertoire of in vivo pre-activated, interleukin-2 (IL-2)-responsive T cells, significant T-cell/TCR clonality was found in 2 out of 4 patients. The clonal T cells represented a minority of the total T-cell population with an estimated frequency of 1 in 300 to 1 in 1000 cells. Molecular characterization of a clonal TCR and the use of a specific TCR V beta MoAb ruled out an over-representation of T cells bearing the same V beta element in the total T-cell population, rendering the involvement of super-antigens in the induction of T-cell clonality in this case unlikely.

Amino Acid Sequence↗
PubMed1991

A double-blind comparison of parenteral methotrexate and parenteral gold in the treatment of early erosive rheumatoid arthritis: an interim report on 102 patients after 12 months.

One hundred two patients with active erosive rheumatoid arthritis (RA) without malalignment or deformities (median disease duration, 14 months) entered a double-blind, randomized study to compare the effects of 50 mg gold sodium thiomalate (GST) with 15 mg methotrexate (MTX) administered intramuscularly for 12 months. Roentgenograms of hands, wrists, and forefeet were taken at baseline and after 6 and 12 months, and 32 joints were evaluated according to Larsen. Sixteen of 50 patients in the MTX group were withdrawn; one patient in the MTX group died of cerebral bleeding that was not related to treatment. Thirty-four GST patients and 44 MTX patients were evaluated for efficacy. Thirty-eight joints were counted. The number oftender and swollen joints, the Lansbury articular index, morning stiffness, activities of daily living (ADL) score, and erythrocyte sedimentation rate improved significantly in both groups without statistical intergroup differences. After 12 months, there was a significant deterioration of the mean Larsen index and the number of joints with erosions without intergroup difference. However, the radiological progression was retarded significantly during the second 6-month period in the gold group, whereas this effect was less pronounced in the MTX group. At 12 months, the progression rate was the same in both groups.

Adolescent↗
PubMed1991

Expression of the CD2 activation epitope T11-3 (CD2R) on T cells in rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and Lyme disease: phenotypic and functional analysis.

CD2R is an activation-associated epitope unmasked by a conformational change of the CD2 cell-surface glycoprotein. In spite of elaborate studies on the role of CD2 and CD2R in adhesion and stimulation of T cells in vitro, no instances of CD2R expression in vivo were known to date. We report high levels of CD2R observed on blood and synovial fluid T cells in rheumatoid arthritis and on peripheral blood T cells in juvenile rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and Lyme disease. In vivo, expression of CD2R was restricted to T cells, not limited to a particular T-cell subset and not correlated with the expression of p55 interleukin 2R (IL-2R) (CD25) or major histocompatibility complex (MHC) class II molecules. When stimulated to proliferation via CD2 or CD3, ex vivo CD2R+ T cells showed the same basic activation requirements as CD2R-T cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

HLA typing in families with multiple cases of rheumatoid arthritis.

Thirty one white patients from 14 families with multiple cases of rheumatoid arthritis (RA) and 42 of their healthy relatives were completely HLA typed. In contrast with class I antigens, the class II antigens DR1 and DR4 were significantly more common in the patients than in a group of 200 healthy local white controls (DR1: 32% v 12%; DR4: 48% v 28%, in patients and controls respectively). Owing to the small number of cases the data from this study were combined with those of published reports. Examination of patients for DR1 and DR4 homozygosity and DR1/4 heterozygosity showed an increase of DR1 homozygous patients, which was not statistically significant. There was no striking deviation from random expectation in haplotype sharing of affected sib pairs. These results are compatible with a dominant influence of DR1 and DR4 in the mode of inheritance. The nearly random haplotype sharing and the molecular relation between DR1 and DR4 support the hypothesis of a direct influence of these antigens in the pathogenesis of RA. Only 68% of the patients in this study possessed either DR1 or DR4, possibly indicating a subtype of RA which is independent of HLA. Clinical and serological variables were measured and indicated no significant difference between DR1 (or DR4) positive and DR1 (or DR4) negative disease. In this small group of patients the clinical course of RA seemed to be determined mainly by other genetic or environmental factors.

Arthritis, Rheumatoid↗
PubMed1991

A double blind randomized parallel trial of intramuscular methotrexate and gold sodium thiomalate in early erosive rheumatoid arthritis.

In a double blind study 57 patients with active erosive rheumatoid arthritis without malalignment or deformities (median disease duration 13 months) were randomly treated with 50 mg gold sodium thiomalate (GSTM) or 15 mg methotrexate (MTX) intramuscularly for 6 months. In the GSTM group, 5/28 patients had to be withdrawn because of side effects; in 2/28 the dose was reduced. In the MTX group, 2/29 were withdrawn, one was lost to followup. The number of swollen joints improved by over 6 in 18/26 (MTX) and in 15/21 (GSTM). Five clinical variables and the sedimentation rate improved significantly in both groups without significant intergroup differences. The radiographs of hands, wrists and forefeet (32 joints evaluated according to Larsen) showed a radiological progression in 11/26 (MTX) and in 8/20 patients (GSTM); however, the deterioration of the mean Larsen index was not significant. While there was no significant difference in effectivity, tolerability was better in the MTX group.

Adolescent↗
PubMed1990

Expression of activation antigens on T cells in rheumatoid arthritis patients.

The aim of our study was to identify differences in cell surface marker expression between T cells taken from the peripheral blood (PB) of healthy individuals and T cells recovered from inflamed joints of rheumatoid arthritis (RA) patients. Out of 118 monoclonal antibodies (MoAbs) directed against activation antigens on haematopoietic cells, 12 MoAbs recognizing nine distinct surface molecules were selected after a screening procedure to study the expression of the corresponding antigens on T cells from the PB, synovial fluid and synovial tissue of RA patients, and also on T cells from PB and spleens of controls. Using two-colour flow cytometry and immunohistology we found the molecules B-C5, CD39, CD40, CD45 R0, CD54, CD76 and potentially 1D11 to be substantially up-regulated on T cells from various body compartments in RA patients. We thus could determine that the cell surface of T cells in RA patients not only differs in MHC class II expression, but also in a number of other activation-associated cell surface molecules from T cells in healthy individuals.

Adult↗