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Biomedical subjects

B A Michel

Publications and source records attributed to B A Michel.

At least 19 recordsLinked to original sources
PubMed1998

Activation of CD4+ and CD8+ T-lymphocytes in bone marrow associated with reduced erythropoiesis in patients with chronic inflammation and anaemia.

We hypothesised that, in "anaemia of chronic disorders" (ACD), a local immune activation in the bone marrow alters erythropoiesis. We determined the activation status of bone marrow T-lymphocytes and the levels of cytokines. Patients (n = 27) with chronic inflammatory diseases and low hemoglobin values who had undergone bone marrow aspiration were divided into 2 groups according to the aetiology of anaemia: (1) unknown or (2) known causes (i.e. iron, folic acid and/or vitamin B12 deficiencies). Cytokines in peripheral blood and bone marrow serum were measured by ELISA and T-lymphocytes were phenotyped by flow cytometry. Peripheral blood from 27 age-matched healthy donors and bone marrow from 3 transplantation donors served as control. The erythrocyte count in the peripheral blood of patients with unknown aetiology of anaemia (group 1) was lower than in patients with known aetiology (group 2). This indicated that group 1 included most patients with ACD. Both groups had active disease, as shown by elevated levels of C-reactive protein and the erythrocyte sedimentation rate. The levels of IL-6 and IL-7 in the peripheral blood were higher in patients of group 1 than in patients of group 2 or normal subjects. The levels of IL-6, IL-7 and TNF-alpha in the bone marrow also were higher in group 1 compared to group 2. The CD4+ and CD8+ T-lymphocytes of the bone marrow showed a more activated phenotype than peripheral blood T-lymphocyte with the number of T-lymphocytes that expressed the early activation marker, CD69, being higher in group 1 than in group 2. A smaller proportion of "naive" cells (CD45RO-, CD69-) was accompanied by a higher proportion of "false naive" cells (CD45RO-, CD69+). In the bone marrow, elevated levels of IL-7 were correlated with fewer "naive" and more "false naive" cells in the CD4+ T-lymphocyte subpopulation. In group 1 only, a significant inverse relation was observed between the erythrocyte counts in blood and the levels of IL-7 in bone marrow. Thus, in patients with unknown aetiology of anaemia--a group including most patients with ACD-, an interrelationship may exist between the local activation of bone marrow T-lymphocytes, increased production of cytokines, and reduced erythropoiesis.

Adult↗
PubMed1998

Differences in nitric oxide production by superficial and deep human articular chondrocytes: implications for proteoglycan turnover in inflammatory joint diseases.

During inflammatory joint diseases, chondrocytes are exposed to cytokines such as IL-1 that induce the synthesis of nitric oxide (NO). Chondrocytes from different zones of the articular cartilage are known to have different metabolic properties. In the present study, we have demonstrated that chondrocytes recovered from the superficial zone of normal, human, articular cartilage synthesize approximately 2 to 3 times as much NO in response to IL-1 as chondrocytes recovered from the deep zone of the same cartilage. Production of NO by normal cartilage in response to IL-1 was also found to decrease with age. Addition of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMA, 1 mM) blocked NO production by cells of both zones. L-NMA completely reversed the suppression of proteoglycan synthesis imposed by IL-1 in deep chondrocytes, but produced only partial reversal in superficial cells. As noted previously, IL-1 failed to elicit a strong catabolic response in cultures of human cartilage. In the presence of L-NMA, however, IL-1 reduced the metabolic t(1/2) of proteoglycans by approximately 50% in both the superficial and deep zones. This suggests that NO has, directly or indirectly, an anticatabolic effect in human cartilage. These data confirm the metabolic heterogeneity of human chondrocytes, and suggest that NO may be involved to different degrees as an endogenous modulator of the turnover of the cartilaginous matrix in different zones of articular cartilage.

Adolescent↗
PubMed1998

Comparison of the WOMAC (Western Ontario and McMaster Universities) osteoarthritis index and a self-report format of the self-administered Lequesne-Algofunctional index in patients with knee and hip osteoarthritis.

OBJECTIVE: To compare the metric properties and validity of German versions of the WOMAC (Western Ontario and McMaster Universities) and a self-administered questionnaire-format of the Lequesne-Algofunctional-Index in patients with osteoarthritis (OA) of the lower extremities. DESIGN: Cross-sectional analysis of the instruments' internal consistency (Cronbach's coefficient alpha) and construct validity (correlation with radiological OA-severity and limitation in range-of-motion) in ambulatory patients and patients before hip arthroplasty. Test-retest reliability was assessed on a subsample after 10 days. RESULTS: Data from 51 patients out of 91 contacted could be analyzed. Twenty-nine patients had knee and 22 patients had hip OA. Both the WOMAC and Lequesne OA-indices and their scales or sections had a satisfactory test-retest reliability (Intraclass correlation coefficient 0.43-0.96). All scales of the WOMAC were internally consistent (Cronbach's coefficient alpha 0.81-0.96) and associated with radiological OA-severity and joint range of motion. However, only the function but not the symptom sections (Cronbach's coefficient alpha knee: 0.55; hip: 0.63) of the self-administered Lequesne OA index were internally consistent for both, patients with knee and hip OA. Also, the symptom components were not or only weakly associated with radiological OA-severity and joint range of motion. CONCLUSIONS: Although our results are based on a German version using a self-report format we may caution using the self-administered Lequesne OA index without prior testing of its metric properties and validity.

Aged↗
PubMed1998

Weighting for joint surface area improves the information provided by a reduced 28-joint articular index of swollen joints.

The objective of our study was to examine whether weighting for joint surface area or recording of simultaneously tender and swollen joints increases the association of a reduced 28-joint articular index with clinical and outcome parameters. In a cross-sectional study we examined 61 consecutive outpatients with RA fulfilling the American Rheumatism Association 1987 revised criteria. Tender, swollen, and simultaneously tender and swollen joints were recorded. The association of 28- and 68-joint articular indices with clinical and outcome parameters were estimated with nonparametric correlation analyses. Weighting for joint surface yielded consistently increased correlation of clinical and outcome parameters with swollen and tender and swollen but not with tender joint counts. The correlation of the 28-joint articular and 68-articular indices with these parameters were similar. In conclusion, weighting for joint surface notably improves the information provided by swollen joint counts, whereas it does not appear to improve the information provided by tender joint counts.

Adult↗
PubMed1998

Isometric muscle strength is an indicator of self-reported physical functional disability in patients with rheumatoid arthritis.

The objective of our study was to examine (1) whether isometric muscle strength contributes to the explanation of the physical functional disability of a rheumatoid arthritis (RA) patient population after accounting for other disease parameters and demographic variables and (2) whether change in isometric muscle strength is an indicator of change in physical functional disability. Sixty-five consecutive patients fulfilling the American Rheumatism Association 1987 revised criteria for RA were included in the study. Isometric muscle strength was measured with a validated Muscle Strength Index (MSI) calculated as the mean score of standardized isometric extension and flexion strength of the knee and elbow joints. Physical functional disability was measured with the physical dimension of the Health Assessment Questionnaire (HAQ). For 56 patients, we could obtain 1 yr follow-up data. Cross-sectionally, there was a significant correlation (r = -0.51, P < 0.01) between the MSI and the HAQ. Muscle strength remained a significant determinant of the HAQ in multivariate analysis accounting for disease and demographic variables. Longitudinally, change in MSI explained additional variance of change in HAQ after accounting for change in pain, the most important correlate of change in HAQ.

Adult↗
PubMed1998

Presence and significance of human parvovirus B19 DNA in synovial membranes and bone marrow from patients with arthritis of unknown origin.

Acute rheumatologic symptoms are frequently associated with human parvovirus B19 (B19) infections. A nested PCR (nPCR) assay was used to test for the presence of parvovirus B19 DNA in synovial fluid and/or synovial membrane specimens obtained from a total of 90 patients with arthritis of unknown origin. Whereas only one out of 73 synovial fluid samples were found positive, 15 (16.7%) out of 90 patients had parvovirus B19 DNA in the synovium. B19 virus DNA was detected in nine bone marrow aspirates subsequently obtained from these 15 patients (60%). Whereas each one of the 15 corresponding blood samples contained anti-B19 IgG antibody, none contained anti-B19 IgM antibody and only one was positive for B19 virus DNA. The blood and synovial fluid samples that contained B19 virus DNA were obtained from the same patient, who also had B19 DNA in synovium and bone marrow. For one patient, two distinct synovial membrane specimens collected 10 months apart tested positive for B19 virus DNA. Parvovirus B19 DNA was also detected in synovial tissue of one out of nine nonarthritic patients serving as control group, who also had anti-B19 IgG circulating antibody. These data illustrate that human parvovirus B19 may persist in bone marrow and synovial tissues of patients with arthritis of unknown origin. In contrast, persistence of B19 virus DNA in synovial fluid is rare. The significance of parvovirus B19 DNA in synovium of healthy patients has to be established.

Adult↗
PubMed1998

Can collagen type II sustain a methotrexate-induced therapeutic effect in patients with long-standing rheumatoid arthritis? A double-blind, randomized trial.

OBJECTIVE: Based on the results of two recently published, randomized, double-blind and placebo-controlled studies, a possible improvement in rheumatoid arthritis disease activity after oral tolerization with triple helical collagen type II has been suggested. The goal of this study was to go one step further and ask the question whether collagen type II can sustain the therapeutic effect induced by methotrexate, the most widely accepted disease-modifying anti-rheumatic drug in patients with long-standing rheumatoid arthritis. METHODS: Ninety-two patients with rheumatoid arthritis on stable therapy with methotrexate were enrolled in a 3 month double-blind, randomized and comparative study to examine the efficacy of oral triple helical collagen type II as compared to continuing methotrexate. The dose of methotrexate (or the respective placebo drug) and of concomitant corticosteroids was not changed and intra-articular corticosteroids were not allowed during the 3 months. The primary study endpoint was disease activity as measured by physician and patients. RESULTS: While patients under ongoing therapy with methotrexate had, as expected, no change in disease activity, almost all parameters of disease activity and outcome in patients under a daily oral dose of 0.5 mg triple helical collagen type II worsened significantly (highly significant difference in swollen joints, between the two groups, P < 0.0001). No significant differences in side-effects between the two groups during the study period could be demonstrated. CONCLUSIONS: Substitution of methotrexate with daily 0.5 mg of triple helical collagen type II in patients with rheumatoid arthritis leads to a significant increase in disease activity, suggesting that oral collagen type II at the given dose is not capable of sustaining the methotrexate-induced anti-inflammatory effect in patients with long-standing rheumatoid arthritis.

Administration, Oral↗
PubMed1998

[Physical therapy in prevention and treatment of osteoporosis].

Osteoporotic fractures, and in particular, hip fractures result in significant morbidity and mortality. Low bone mass is the main risk factor of enhanced bone fragility, resulting in an increased risk for hip fracture. Bone density of osteoporotic women with and without hip fractures show a considerable overlap. Therefore, other bone-independent factors also play an important role for the development of hip- and other osteoporotic fractures. One other important factor is falling. In 90% of hip fractures falling was involved [10-15], but only 5% or less of these falls resulted in a subsequent fracture. The view that adequate exercise is beneficial for skeletal health of children and for prevention and treatment of osteoporosis in adults is supported primarily by two lines of evidence: longitudinal and cross-sectional trials in children and young adult athletes showing a significant increase of muscle- and bone mass after strenuous (children) or chronic exercise (athletes) as compared to normally active (children) or sedentary control subjects. What are the potential benefits and limits of specific exercise programs with respect to bone mass, prevention of falls and fractures? In this review these questions are discussed and a specific exercise program in osteoporotic patients with fractures is delineated.

Adolescent↗
PubMed1997

[Sports in patients with systemic inflammatory musculoskeletal diseases].

Local and systemic inflammatory mechanisms and immobilisation, perhaps secondarily intensified by corticosteroid treatment, very often produce reduced load capacity of the tissues. Pain, swelling of the joints, muscular atrophy and instability favour such development. Increased activity of the disease rapidly leads to general discomfort and unfitness. Drugs generally help to reduce the inflammatory activity. To increase and restore the musculo-skeletal load capacity, however, the patient must undergo physiotherapy and exercises adapted to the disease activity and, if he/she so desires adequate sporting activity.

Female↗
PubMed1997

[Traumatic finger polyarthrosis in judo athletes: a follow-up study].

Osteoarthritis is the most common joint disease. In addition to known risk factors e.g. genetics, age and hormonal status it has been suggested that chronic-repetitive micro- and substantial (macro-) injury may play an important pathogenetic role. In a longitudinal case-study we examined Judo-players for clinical and radiological changes of the finger joints over the course of 16 years. All examined 8 players demonstrated soft tissue changes including Heberden nodes and radiological changes typical for osteoarthritis of the finger joints. Changes were symmetrical and were not restricted to joints with tendon ruptures or fractures in the anamnesis. Degenerative changes were progressive and more pronounced in active players. Subjectively, symptoms were usually mild. Extensive Judo seems to be a risk factor for the development of osteoarthritis of the finger joints due to chronic-repetitive micro- and substantial (macro-) injury.

Adult↗
PubMed1997

Small fragments of cartilage oligomeric matrix protein in synovial fluid and serum as markers for cartilage degradation.

We determined the tissue distribution of cartilage oligomeric matrix protein (COMP) in man and evaluated COMP in synovial fluid (SF) and serum. COMP was purified from human articular cartilage. Polyclonal antibodies were used to detect COMP in tissue cryosections and protein extracts. COMP was determined quantitatively and qualitatively in SF and serum by competitive enzyme-linked immunosorbent assay and immunoblotting. Knee joint SF was taken from nine cadaveric and six living controls, 52 patients with osteoarthritis (OA), 85 patients with rheumatoid arthritis (RA) and 60 patients with other forms of inflammatory arthritis. The degradative potential of SF on native COMP was tested in vitro. The highest concentrations of COMP were measured in articular cartilage and meniscus, the lowest in rib and trachea. Compared with controls, the concentrations of COMP in SF and serum were elevated in 36 and 50% of the patients. A total of 84% of patients with RA and 60% of patients with other forms of inflammatory arthritis showed significant amounts of low-molecular-weight COMP fragments (50-70 kDa) in SF. In contrast, SF fragments were present in only 21% of the OA patients. Furthermore, 13% of SF taken from patients with RA or other forms of inflammatory arthritis were able to degrade COMP in vitro. Using inhibitors, the involvement of serine proteinases could be demonstrated in only 8% of the cases. Based on these results, the absolute levels of COMP in SF and serum, and its fragmentation pattern in SF, seem to be promising as markers of joint tissue metabolism.

Adult↗
PubMed1997

Children's thinking in the wake of Challenger.

OBJECTIVE: The Challenger spacecraft explosion in 1986 offered an opportunity to study the thinking of normal children after a sudden and distant disaster, differences in thinking among children of different levels of emotional concern and different ages, and changes in their thinking over time. METHOD: The authors studied six thinking patterns known to characterize childhood posttraumatic stress disorder and four additional hypothesized patterns in 153 randomly selected children of Concord, N.H. (who watched the explosion on television) and Porterville, Calif. (who heard about it later). They compared the structured-interview responses of the more involved (East Coast) and less involved (West Coast) children, of the latency-age children and the adolescents, and of the children initially (5-7 weeks after the explosion) and 14 months later. RESULTS: The children exhibited the 10 predictable thinking patterns. They initially defended themselves, denying the reality of the explosion. They later fantasized about it. They tried to cope by seeking additional information on their own, at home, and at school. Most children talked about Challenger, but a minority of the latency-age youngsters avoided related talk and thoughts. The adolescents experienced more paranormal thinking, philosophical changes, and negative attitudes. Over the year, omens, paranormal experiences, and Challenger-based fantasies tended to disappear, but negative views about institutions and the world's future held steady or increased. CONCLUSIONS: The children's thinking followed predictable patterns. A higher degree of emotional involvement (East Coast children) was strongly linked to these thinking patterns, as was being an adolescent. Distant disasters appear to set up commonalities of thought that might come to characterize certain generations of children.

Adaptation, Psychological↗
PubMed1997

Systemic levels of the T cell regulatory cytokines IL-10 and IL-12 in Bechçet's disease; soluble TNFR-75 as a biological marker of disease activity.

OBJECTIVE: To analyze the levels of the T cell regulatory cytokines interleukin 10 (IL-10) and IL-12 in plasma of patients with Behçet's disease (BD), and to assess the value of cytokines and cytokine antagonists as biological markers of disease activity. METHODS: Sera/plasma of 66 consecutive outpatients with established diagnosis of BD were analyzed for the presence of IL-2R, IL-6, tumor necrosis factor-alpha (TNF-alpha), soluble (s) TNF receptor (R)-55, sTNFR-75, IL-10, and IL-12 using immunological methods. Additional laboratory measurements included erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Data from the history and clinical examination were recorded to correlate cytokine levels with clinical markers of disease activity. RESULTS: 18 patients had inactive (Group I), 36 had mildly active (Group II), and 12 patients had active BD (Group III). IL-10 was elevated in 42 plasma samples (64%). The percentage of samples containing IL-10 and the median levels of IL-10 of the 3 patient groups did not differ significantly. IL-12 was detectable in plasma of 9 patients: One from Group I (5%), 3 from Group II (8%), and 5 from Group III (41%). IL-12 correlated with disease activity (difference between Groups I and III, p = 0.02, between Groups II and III, p = 0.008). ESR in patients with active disease and mildly active disease was significantly higher than values in patients with inactive disease (p = 0.03, p = 0.02, respectively), while median CRP levels were significantly different between Group I and Group III only (p = 0.006). sTNFR-75 levels were significantly different between Groups II and III (p = 0.003) and between Groups I and III (p = 0.008). CONCLUSION: The elevation of plasma IL-10 in the majority of patients and the correlation of IL-12 plasma levels with disease activity suggest a pathogenic role of a TH1-type immune response in active disease. In addition, the correlation of sTNFR-75 levels with disease activity indicates that sTNFR-75 may serve as a biological marker of disease activity in BD.

Adolescent↗
PubMed1996

CD45 isoforms expression on CD4+ and CD8+ peripheral blood T-lymphocytes is related to auto-immune processes and hematological manifestations in systemic lupus erythematosus.

We investigated whether, in systemic lupus erythematosus (SLE), the CD45 isoforms expression on peripheral blood T-lymphocytes (T-PBL) is related to the auto-immune processes and hematological manifestations. The CD45RA/RO patterns of CD4+ and CD8 bright+ T-PBL were determined by three-colour flow cytometry. The serum levels of anti-nuclear (ANA), anti-double stranded DNA (ds DNA) and anti-cardiolipin (CL) autoantibodies were quantified by ELISA. The hematological parameters were routinely assessed. 72% of SLE patients (n = 29) had reduced lymphocyte counts, which correlated with more severe physician's assessment of disease activity, increased ANA and anti-ds DNA auto-antibodies. The lymphopenia preferentially affected the CD4+ T-PBL and, among them, the "naive" CD45RA+, RO- cells. Thus, compared with healthy women (n = 29), SLE patients had less naive and more "transient" CD45RA+, RO+ cells among CD4+ T-PBL. Meanwhile, on average, the CD45 isoforms expression on CD8+ T-PBL was unchanged. Interestingly, in 3 patients who were repeatedly evaluated, increases of transient CD8+ T-PBL paralleled the elevation of anti-ds DNA. In addition, high anti-CL was associated with more transient CD4+ and CD8+ T-PBL. The loss of naive and increase of transient CD8+ T-PBL was associated with increased disease activity and possibly hemolytic anemia. Thus, in SLE, the enhanced phenotypic switch from naive CD45RA+, RO- to "memory" CD45RO+ T-PBL patterns paralleled the auto-immune processes characteristic of this disease.

Adult↗
PubMed1996

[Is misoprostol effective in NSAID-induced gastrointestinal complications?].

Misoprostol, a synthetic prostaglandin E1, has been shown to reduce both gastric lesions and clinically relevant gastrointestinal events in patients taking NSAIDs. In patients with multiple risk factors gain in quality of life by avoidance of gastric ulcers seems to offset the loss in quality of life due to diarrhea, the most important misoprostol side effect. From a clinical-epidemiological point of view misoprostol prophylaxis thus seems reasonable in patients with multiple risk factors. Since non-use due to diarrhea varies highly among patients, individual preferences should be considered in the decision making process. From an economic point of view misoprostol prophylaxis seems justified in patients with multiple risk factors. In such patients misoprostol prophylaxis may indeed be cost-saving. However, this needs to be confirmed in further economic evaluations based on newly available effectiveness data and better data on patient preferences from large and representative samples.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

pH-dependent hysteretic behaviour of human myeloblastin (leucocyte proteinase 3).

Human myeloblastin (leucocyte proteinase 3) showed a very slow approach to the steady-state velocity when the pH was rapidly increased from 3.2 to 7.0. The kinetic mechanism of this hysteretic process was interpreted as a slow conformational change of myeloblastin from an inactive form at acidic pH to the active form at neutral pH. The transition between the two enzyme forms could occur spontaneously in the absence of substrates with a first-order rate constant of 0.0033 s-1. In the presence of peptide substrates activation occurred more rapidly: the observed rate constant was linearly dependent upon the substrate concentration and contained a contribution of the spontaneous as well as of the substrate-dependent process, whose second-order rate constant was characteristic of the particular substrate. This pH-dependent phenomenon of hysteresis on the part of myeloblastin, that is not manifested by the closely related leucocyte elastase, may have a physiological control function during phagocytosis by damping the rate of interconversion between enzymically inactive and active enzyme conformations.

Humans↗