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Biomedical subjects

M Schattenkirchner

Publications and source records attributed to M Schattenkirchner.

At least 37 records · Page 2Linked to original sources

Predominance of mononuclear cells expressing the chemokine receptor CCR5 in synovial effusions of patients with different forms of arthritis.

OBJECTIVE: To study the role of the chemokine receptors CCR5 and CCR2 in patients with arthritis. METHODS: CCR5 expression on peripheral blood leukocytes was compared with the expression on leukocytes isolated from the synovial fluid of 20 patients with different rheumatic joint diseases. Three additional samples were studied for CCR2 expression. The expression of chemokine receptors on blood and synovial fluid leukocytes was determined by 3-color flow cytometry analysis. To test CCR5 receptor down-modulation from the cell surface, leukocytes were incubated in vitro with a RANTES (regulated on activation, normal T cell expressed and secreted) derivative, aminooxypentane (AOP)-RANTES. Patients were genotyped for the delta32 CCR5 deletion by polymerase chain reaction. RESULTS: A high percentage of CCR5-expressing CD4+ and CD8+ T cells (74% and 81%, respectively), monocytes (51%), and natural killer cells (35%) was found in the synovial fluid of all patients, whereas in the peripheral blood, only a small percentage of these cells expressed CCR5 (13%, 32%, 7.8%, and 4%, respectively). Infiltration of CCR5-positive leukocytes was not reduced in CCR5-heterozygous patients. A similar, but less pronounced, distribution was observed for CCR2-positive T cells. In vitro, CCR5 was completely down-modulated on synovial fluid leukocytes by AOP-RANTES. CONCLUSION: The predominance of CCR5-positive mononuclear cells in the synovial effusions of patients with arthritis suggests an important role for CCR5 in the process of joint inflammation, and identifies CCR5 as a possible new target for therapeutic intervention.

Adolescent↗

[RS3PE-syndrome].

The RS3PE syndrome (Remitting Seronegative Symmetrical Synovitis with Pitting Edema) is a manifestation of rheumatoid arthritis in the elderly with a good prognosis. It usually presents as an acute, symmetric polysynovitis with edema of the dorsum of the hands and feet. Anti-inflammatory treatment with corticosteroids leads to prompt improvement. We describe the case of an 81 year old man with a primarily unilateral manifestation involving the right hand. A thrombosis of the axillary vein was suspected. Within a few days he developed a pitting edema of the dorsum of the other hand. Movement of both shoulders and wrists was painful. Low-dose corticosteroid therapy resulted in a rapid improvement of the edema and the inflammatory symptoms.

Adrenal Cortex Hormones↗

Leptin serum levels are not correlated with disease activity in patients with rheumatoid arthritis.

Leptin, the ob gene product, has been proposed as a mediator of inflammatory cytokine-dependent decreased food intake and cachexia in rodents. In humans, leptin serum levels increase after administration of tumor necrosis factor-alpha (TNF-alpha) or interleukin-2 or during septicemia. However, the effect of human chronic inflammatory disease on serum leptin is unknown. We therefore determined the serum leptin level (radioimmunoassay), body mass index (BMI), percent body fat ([%BF] bioelectrical impedance analysis), and disease activity (Disease Activity Score [DAS]) in 58 patients with rheumatoid arthritis (RA) and 16 controls. The BMI, %BF, serum leptin, and ratio of leptin to %BF (leptin/%BF) did not differ significantly in 25 patients with moderate RA activity (DAS, 3.6 +/- 0.5), 33 patients with low RA activity (DAS, 1.8 +/- 0.5), and controls. A positive correlation for serum leptin and %BF was detected in all groups. Our data indicate that in RA, a human chronic cytokine-mediated inflammatory disease, the serum leptin level is directly related to %BF but not to disease activity.

Adipose Tissue↗

Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components.

OBJECTIVES: To investigate the potential clinical benefit of a combination therapy. METHODS: 205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying antirheumatoid drugs previously, with an early (< or = 1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68). RESULTS: The mean changes in the DAS during the one year follow up of the study was -1.15, -0.87, -1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007). CONCLUSION: This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.

Antirheumatic Agents↗

[Severe toe gangrene as an early manifestation of Wegener granulomatosis in a young patient].

Gangrene of digits is a very rare manifestation of Wegener's granulomatosis (WG). We report a case of a 29-year-old woman with nonspecific symptoms like fever, weight loss, arthralgia, arthritis and high systemic inflammatory signs. On the grounds of a presumed infection the patient was treated with antibiotics which showed no effect. Within short she complained of pain and paresthesia of the right foot with a rapid lividity. Angiography demonstrated multiples stenoses and multisegmental occlusions of the lower leg arteries. Together with renal and pulmonal symptoms a WG was suspected, the diagnosis being confirmed by kidney biopsy and positive cANCAs. A few months after starting a combined therapy with cyclophosphamide and corticosteroids the patient showed a partial remission with a residual toe gangrene. Comparing the five worldwide reported cases with digital gangrene and our presentation there is a concordance of all in the occurrence of an extremely high disease activity together with a glomerulonephritis. The findings of p-ANCAs in our patient and positive Hbs antigen in another case of WG with digital gangrene suggests a relation to panarteriitis nodosa, where gangren is more common.

Adult↗

[A proposal for the MR staging of early rheumatoid arthritis in the metacarpophalangeal and proximal interphalangeal joints].

PURPOSE: MRI can demonstrate pathology of joint disease in the early course of rheumatoid arthritis prior to destructions seen on conventional radiographs. In a prospective study, we tried to develop a systematical classification of joint pathology demonstrated by MRI, which would be essential for scoring the course of the disease. PATIENTS AND METHOD: Metacarpophalangeal and interphalangeal joints of 48 patients suffering from early rheumatoid arthritis (mean disease duration: 6.4 months) were evaluated by MRI using a high-resolution transmitter-receiver coil. Examinations included 2 mm sliced T2-, T1- and gadolinium enhanced T1-SE sequences in coronal and axial orientation. In consideration of pathological findings on MRI and histopathogenetical pathways of destruction in rheumatoid arthritis a MR-score (0-5) was established. RESULTS: This allowed to score each joint examined: score 0 (normal) in 47.8%/49.5%, score 1 in 35.5%/50.5%, score 2 in 4.2%/0%, score 3 in 10.8%/0%, score 4 in 1.5%/0% of the metacarpophalangeal/interphalangeal joints, respectively. CONCLUSIONS: Using the MR-score a relative individual destruction number can be calculated, which may be used to follow up patients in the early course of rheumatoid arthritis (e.g. drug therapy studies). The presented MR scoring system has to be evaluated further in longitudinal studies and must be correlated to radiographical and clinical findings.

Adult↗

Meloxicam: a selective COX-2 inhibitor non-steroidal anti-inflammatory drug.

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) that selectively inhibits the inducible isoform of the cyclo-oxygenase (COX)-2 enzyme. This enzyme has a major role in mediating the inflammatory response, while synthesis of prostaglandins required for normal physiological functioning of the stomach and kidneys is under the control of the constitutive isoform, COX-1. Other NSAIDs in clinical use show varying degrees of selectivity towards COX-1. Only meloxicam and (albeit to a lesser extent) nimesulide could be described as selective for COX-2. In comparative trials of patients with osteo- and rheumatoid arthritis, meloxicam has been found to be at least as effective as other NSAIDs, but with a greatly reduced incidence of gastrointestinal side-effects. There is no evidence that meloxicam causes any deterioration in renal function in patients with moderate degrees of renal failure, and no evidence of drug accumulation with continued use. Meloxicam's half-life of 20 h makes it ideal for once daily administration, and it is 99% converted to inactive metabolites prior to excretion. No clinically significant drug interactions have been detected, making it suitable for use in patients with co-existing pathology. Meloxicam's safety and tolerability make it a significant advance in the treatment of rheumatic disease.

Journal Article↗

Routine molecular genotyping of HLA-B27 in spondyloarthropathies overcomes the obstacles of serological typing and reveals an increased B *2702 frequency in ankylosing spondylitis.

OBJECTIVE: To evaluate the reproducibility and reliability of polymerase chain reaction (PCR) in HLA-B27 typing compared to the conventionally used microlymphocytotoxicity test (MLCT). To determine the HLA-B27 subtype frequencies (B*2701-B*2709) in patients with HLA-B27 associated disease and healthy persons using sequence specific oligonucleotides (SSO). METHODS: 398 consecutive patients were HLA-B27 typed by MLCT and PCR. Subtyping by SSO was performed in 142 patients with HLA-B27 associated disease [ankylosing spondylitis (AS) n = 38, reactive arthritis 44, undifferentiated spondyloarthropathy (uSpA) 45, psoriatic arthritis 15] and 125 healthy HLA-B27 controls. RESULTS: MLCT identified 61 HLA-B27 positive patients (15.3%); PCR identified 78 positive patients (19.6%). MLCT gave false negative results for 8 patients (2.0%) and false positives for a further 7 (1.8%). Only subtypes B*2702 and B*2705 were present in patients and controls. Overall frequencies of B*2702 in patients and controls were 14.1 and 9.6%, respectively. The B*2702 frequency was significantly (pcorr. < 0.04) higher in AS (23.7%) and lower in uSpA (6.7%) patients. CONCLUSION: HLA-B27 typing by PCR is reliable and reproducible and therefore recommended for routine typing. It overcomes the obstacles of serological typing, i.e., equivocal results and cross-reactivity. In addition, subtype frequencies (B*2702 and B*2705) are equally distributed among patients and controls, although subtype B*2702 seems to be more frequent in AS and less so in uSpA.

Amino Acid Sequence↗

A six-month double-blind trial to compare the efficacy and safety of meloxicam 7.5 mg daily and naproxen 750 mg daily in patients with rheumatoid arthritis.

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which preferentially inhibits cyclooxygenase-2 over cyclooxygenase-1. A double-blind parallel-group trial compared meloxicam 7.5 mg once daily (n = 199) with naproxen 750 mg (n = 180) in rheumatoid arthritis. There was no significant difference between the groups regarding the primary efficacy variables (global efficacy assessment by patient and investigator, number of painful/tender and swollen joints) and eight of the ten secondary efficacy endpoints. Only the swollen joint severity index and the number of discontinuations due to lack of efficacy favoured naproxen 750 mg significantly over meloxicam 7.5 mg. Meloxicam was better tolerated in the gastrointestinal (GI) tract, with fewer GI adverse events in the meloxicam-treated group (30.3%) than in the naproxen-treated group (44.7%), where two patients developed ulcers. No ulcers were seen in meloxicam patients. Significantly more patients discontinued due to GI adverse events in the naproxen group. Additionally, there was a significant decrease in haemoglobin and a significant increase in serum creatinine and urea in the naproxen group compared with the meloxicam group. In conclusion, meloxicam 7.5 mg once daily is a promising treatment in rheumatoid arthritis, with efficacy comparable to naproxen 750 mg. Meloxicam has the advantage of a significantly lower incidence of GI and renal side effects.

Adult↗

Arthritis after hepatitis B vaccination. Report of three cases.

Side effects of hepatitis vaccination are rare. Only a few cases of arthritis after hepatitis vaccination have been published. We report on three cases of vaccination-induced arthritis with different resulting disease. Two cases show the pattern of reactive arthritis. None of them was associated with HLA-B27. In the third case onset of rheumatoid arthritis was triggered by hepatitis vaccination. These three cases show that arthritis after hepatitis B vaccination probably is more common than reported so far, especially in a genetically predisposed subject (two of our patients expressed HLA-DR4).

Adolescent↗

Treatment of psoriatic arthritis with auranofin and gold sodium thiomalate.

Forty-two patients with psoriatic arthritis were included in a multicenter, double-blind trial comparing auranofin and gold sodium thiomalate (GST) for 6 months, followed by a 6-month open treatment. Fifty-two percent of the patients on auranofin and 33% on GST were able to complete the 1-year course of therapy. As a result of the study we conclude that both gold compounds are effective agents in the treatment of psoriatic arthritis. Degree of improvement of arthritis was better in the GST group, but the number of improved patients was greater in the auranofin group. Two patients on auranofin were withdrawn for side effects (one diarrhoea, one worsening of psoriasis) and 5 on GST (rash 2, total loss of appetite 1, exacerbation of psoriasis 2). Comparing the side effects of both compounds, auranofin is less likely to aggravate the psoriatic condition or result in withdrawal of patients for adverse reactions.

Adult↗

Comparison of cyclosporin A and azathioprine in the treatment of rheumatoid arthritis--results of a double-blind multicentre study.

In a prospective randomized double-blind multicentre study cyclosporin A (CyA) and azathioprine (AZA) were compared in 117 patients with rheumatoid arthritis (starting dose CyA 5 mg/kg, AZA 1.5-2 mg/kg). The six-month treatment period was similarly completed in 92 patients with good clinical results in both groups (mean improvement rate CyA vs. AZA: Ritchie-Index 8.2 vs. 7.7, morning stiffness 41.6 vs. 28.4 min., grip strength 10.9 vs. 15.2 mmHg, swollen joint count 28.9 vs. 27.9%). Treatment was discontinued prematurely in 12 patients in each group (CyA: 2 deaths not related to drug, 1 lack of effect, 9 adverse reactions--AZA: 2 drop-outs, 1 lack of effect, 9 adverse reactions). Altogether effectivity and tolerability were equal in both treatment groups with the exception of an increase in blood pressure and serum creatinine which occurred only in the CyA group.

Arthritis, Rheumatoid↗

[Gout tophi and Heberden nodules in hyperuricemia].

The tophus is a characteristic and pathognomonic sign of chronic gout. Before effective drugs were available for the treatment of hyperuricaemia about 50-60% of patients with gout developed clinically and radiologically apparent urate crystal deposits. Clinical cutaneous manifestations of chronic gout are now rarely observed. However, the presence of degenerative tissues, as in idiopathic osteoarthritis of the fingers, may predispose to the deposition of urate crystals. We report on a patient with secondary--probably diuretic-induced--hyperuricaemia and gout tophiin Heberden's nodes.

Aged↗