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Biomedical subjects

D Nordström

Publications and source records attributed to D Nordström.

At least 19 recordsLinked to original sources
PubMed2000

A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis.

OBJECTIVE: To compare the clinical efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis (RA). METHODS: In this multicentre, double-blind trial, 999 subjects with active RA were randomized to leflunomide (n = 501; loading dose 100 mg/day for 3 days, maintenance dose 20 mg/day) or methotrexate (n = 498; 10-15 mg/week) for 52 weeks. After 1 yr the subjects could choose to stay for a second year of double-blind treatment. The primary end-points were tender and swollen joint counts and overall physician and patient assessments. Analyses were of the intent-to-treat group. RESULTS: After 1 yr, the mean changes in the leflunomide and methotrexate groups, respectively, were -8.3 and -9.7 for tender joint count; -6.8 and -9.0 for swollen joint count; -0.9 and -1.2 for physician global assessment; -0.9 and -1.2 for patient global assessment; -14.4 and -28.2 for erythrocyte sedimentation rate. Improvements seen with methotrexate were significantly greater than those with leflunomide. No further improvement occurred after the second year of treatment and the distinction between the two treatments in terms of tender joint count and patient global assessment was lost. During the first year of treatment, a small and equivalent degree of radiographically assessed disease progression was seen with both drugs. After 2 yr, disease progression was significantly less with methotrexate. The most common treatment-related adverse events in both groups were diarrhoea, nausea, alopecia, rash, headache, and elevated plasma liver enzyme levels. Over 2 yr, 21 subjects receiving methotrexate were withdrawn due to elevated plasma liver enzymes vs eight subjects taking leflunomide. Two drug-related deaths from pulmonary causes were recorded with methotrexate vs no drug-related deaths among the subjects receiving leflunomide. CONCLUSIONS: Both leflunomide and methotrexate are efficacious for prolonged treatment of RA. At the doses used, some clinical benefit of methotrexate over leflunomide was observed in the first year of treatment. This benefit must be weighed against the potential toxicity of this drug when used without folate supplementation.

Adolescent↗
PubMed1998

Anti-collagenolytic mechanism of action of doxycycline treatment in rheumatoid arthritis.

Tetracyclines exert, independently of their antimicrobial activity, anti-collagenolytic effects by inhibiting activities of human interstitial collagenases and by preventing the oxidative activation of latent pro-collagenases. We tested the clinical response to a 3-month doxycycline in concert with collagenase activity in 12 rheumatoid arthritis (RA) patients. Patients received 150 mg/day of doxycycline for 3 months. Clinical assessments at zero, six and 12 weeks comprised classification of the functional class, joint score index, Hb, CRP, ESR, health assessment questionnaire, visual analogue scale (VAS) of pain, pain disability index, comprehensible psychopathological rating scale (CPRS), SDS-PAGE laser densitometric collagenase activity measurements and Western blots. Significant reductions were seen in joint score index (P < 0.01), pain VAS (P < 0.05) and some CPRS parameters. Furthermore, collagenase activities measured from saliva by quantitative SDS-PAGE electrophoresis were significantly reduced during the 12-week intervention (P < 0.01). Western blots demonstrated intact 75-80 kDa enzyme protein (classic neutrophil collagenase), but also a newly discovered mesenchymal, less glycosylated 40-55 kDa MMP-8 subtype of fibroblast/chondrocytic origin. These results indicate that the documented favourable clinical response may in part be due to in vivo inhibition of classic neutrophil and mesenchymal collagenase/MMP-8 activities produced by doxycycline. This anti-collagenolytic doxycycline effects is mediated through inhibition of the enzyme activity and not through degradation of the enzyme, which may have contributed to the reportedly reduced tissue destruction, as has been seen in clinical studies concerning RA as well as reactive arthritis.

Anti-Bacterial Agents↗
PubMed1997

Availability of iron and degree of inflammation modifies the response to recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis.

Forty-six patients with rheumatoid arthritis (RA) and documented anemia of chronic disease (Hb < 100/110 g/l) were randomized to receive either human recombinant erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or placebo (n = 10) for 12 weeks in a multicenter study. An adequate response was defined as elevation of Hb > or = 120 g/l. Relevant clinical and laboratory assessments were made to evaluate efficacy and secure safety. A significant elevation in Hb from week 10 onwards was noted in twenty-six patients (five drop-outs) out of nine patients receiving placebo (one drop-out) (12 +/- 1.2 g/l vs 4 +/- 0.5 g/l; Hb elevation from 95 g/l to 107 g/l vs 93 g/l to 97 g/l, P < 0.05). Only 14.6%, however, were considered responders according to preset criteria. In the responders a lower initial CRP, a significant reduction in ESR but not in CRP was seen compared to the remaining r-HuEPO group. A significant elevation of energy level was noted in the r-HuEPO group; otherwise, no differences in clinical variables were seen. No serious adverse effects were noted. When analyzing patients receiving oral iron in combination with r-HuEPO and adding five additional, openly selected patients receiving both adequate iron supplementation and r-HuEPO, there was a significant weekly elevation of Hb from week 8 onwards in favor of combination therapy over the ones only receiving r-HuEPO (18 +/- 1.1 g/l vs 7 +/- 1.1 g/l, P < 0.05). The initial six responders had now reached ten of whom seven belonged to the combination therapy group. Response to r-HuEPO in RA patients appears to be dependent on availability of iron and on the degree of inflammation. If r-HuEPO treatment is considered, iron deficiency should always be corrected and strenuous efforts should have been made to control the disease itself.

Adult↗
PubMed1996

Similar pleural fluid findings in pleuropulmonary tularemia and tuberculous pleurisy.

Biochemical and cellular characteristics of pleural fluid from two patients with pleuropulmonary tularemia and 39 patients with tuberculous pleurisy were compared. High pleural fluid concentrations of adenosine deaminase, lysozyme, and beta 2-microglobulin occurred in both diseases. As is the case with tuberculous pleural effusions, pleural fluid in tularemia showed an abundance of lymphocytes, predominantly CD4-positive T lymphocytes. The similar pleural fluid findings suggest analogous local pathogenetic mechanisms in tularemia and tuberculosis. In the diagnostic evaluation of a lymphocyte-rich exudative pleural effusion with a high adenosine deaminase concentration, a possible cause to consider is tularemia.

Aged↗
PubMed1995

Effects of prolonged tourniquet ischaemia and short-term venous stasis on plasma endothelin-1 levels in man.

In vitro studies have indicated increased endothelial release of endothelin during tissue and cellular hypoxia. Therefore, we studied the effect of tourniquet ischaemia and venous stasis on plasma endothelin-1 (ET-1) levels in humans in vivo. The effect of hypoxia on plasma ET-1 levels in 16 patients subjected to an orthopaedic operation and six healthy volunteers was studied by (a) tourniquet ischaemia, in which a limb is totally emptied of blood and kept ischaemic by means of a pneumatic tourniquet, and (b) venous stasis in an upper arm. The mean (SEM) basal plasma ET-1 concentration in the patients subjected to tourniquet ischaemia of a lower limb was 4.1 (1.0) pg ml-1. No significant change in plasma ET-1 levels during or after tourniquet ischaemia was found. The mean (SEM) plasma ET-1 concentration in six healthy subjects prior to venous occlusion in the right upper arm was 3.3 (0.7) and 2.7 (0.3) pg ml-1 in the right and left arm, respectively. A significant increase in plasma ET-1 concentration after 20 min was observed in the arm subjected to venous stasis, but not in the other, control, arm. Mean arterial blood pressure did not change significantly. Local tissue hypoxia may not be an important stimulus for ET-1 release in humans in vivo, whereas short-term venous occlusion in an upper arm leads to local release of ET-1 by an as yet unknown mechanism.

Adult↗
PubMed1994

Symptomatic lumbar spondylolysis. Neuroimmunologic studies.

OBJECTIVES: This study characterized the defect using neuroimmunologic and inflammatory cell analysis. SUMMARY OF BACKGROUND DATA: Spondylolysis/spondylolisthesis is thought to be caused by a congenital weakness and mechanical stress causing a fracture associated with defective healing. Most of the spondylolysis patients are asymptomatic and the mechanisms of pain in symptomatic patients are unknown. METHODS: Tissue from the spondylolysis defect was collected from seven patients undergoing posterolateral fusion operations. RESULTS: Histologic examination disclosed delayed union/pseudoarthrosis with fibroblasts and macrophages in a pseudosynovial lining membrane and occasional perivascular infiltrates containing mainly CD2 lymphocytes and CD11b monocytes/macrophages. In a vascularized connective tissue stroma PGP 9.5, synaptophysin and neurofilament staining disclosed perivascular nerves, which did not extend to the synovial lining layer and which mainly represented postganglionic sympathetic nerve fibers but also calcitonin gene-related peptide and substance P containing sensory fibers. CONCLUSIONS: Pain in spondylolysis/spondylolisthesis might derive from the spondylolytic defect itself, probably from stretching of the local neural elements rather than from their sensitization/stimulation by local inflammatory mediators. The resemblance of neuroimmunohistochemical changes compared with those reported in the nonunion of long bones and the sparsity of stromal innervation, indicate that the characteristic defective healing is in part due to lack of neurogenic influences.

Adolescent↗
PubMed1994

Local immune inflammatory response to infected total hip and knee replacements.

We studied the tissue response for periprosthetic pseudosynovial tissue in seven patients with a purulent endoprosthetic infection and six patients with common prosthesis loosening, using specific monoclonal antibodies in avidin-biotin-peroxidase complex staining. In infected cases, proline 4-hydroxylase positive fibroblasts dominated the stroma of the vascularized periprosthetic connective tissue, whereas diffuse local infiltrations of mononuclear cells characterized the cellular histological overview. Local cellular response consisted of CD11b and MHC locus II antigen-positive immunoreactive monocytes/macrophages and of T lymphocytes, mostly of the CD4 subset. Only a few CD25-positive cells could be detected. The local cellular response in six patients with prosthesis loosening of nonbacterial origin was mild, showing a sparse perivascular infiltration of CD11b- and Ia-positive monocytes/macrophages and CD4/CD8-positive T lymphocytes in a proportion of 2:1. Only occasional CD15- or lactoferrin-positive neutrophils and CD25-positive lymphocytes could be detected. Our results from chronically infected joint replacements suggest that neutrophils, being virtually absent in the tissue compartment, do not contribute to pathological events in the "pseudojoint" cavity, whereas local tissue response consists of a mononuclear inflammatory cell reaction of a macrophage-dependent foreign-body type.

Adult↗
PubMed1994

In vivo inhibition of human neutrophil collagenase (MMP-8) activity during long-term combination therapy of doxycycline and non-steroidal anti-inflammatory drugs (NSAID) in acute reactive arthritis.

We studied the in vivo effect of long-term doxycycline treatment combined with NSAID on human interstitial collagenases, other matrix metalloproteinases, serine proteinases, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and lactoferrin from saliva and serum during the course of acute reactive arthritis (ReA). Collagenase activity and serine proteases (elastase-like, cathepsin G-like and trypsin-like activities) of saliva (n = 10) and gelatinase, lactoferrin and TIMP-1 of saliva (n = 10) and serum (n = 10) samples before and after 2 months doxycycline treatment, combined with NSAID, were studied by quantitative SDS-PAGE assay, ELISA assay and by spectrophotometric assay. The cellular source and molecular forms of salivary collagenase were characterized by immunoblotting using specific antisera. We found that activities of total and endogenously active interstitial collagenase reduced significantly. The salivary collagenase was found to originate from neutrophils. No fragmentation of either pro 75-kD and active 65-kD MMP-8 was detected after 2 months doxycycline treatment. However, during 2 months doxycycline and NSAID treatment no reduction of salivary and serum gelatinase, lactoferrin and TIMP-1-levels and salivary serine protease activities were detected. The in vivo inhibition of collagenase (MMP-8) activity during long-term doxycycline therapy in human saliva containing inflammatory exudate of ReA patients may contribute to the reduced tissue destruction observed in recent clinical and animal model studies in arthritides during long-term doxycycline/tetracycline treatment.

Adult↗
PubMed1994

Reduction of matrix metalloproteinase 8-neutrophil collagenase levels during long-term doxycycline treatment of reactive arthritis.

The aim of this work was to determine whether human polymorphonuclear neutrophilic interstitial collagenase (matrix metalloproteinase 8 [MMP-8]) levels are reduced during long-term doxycycline treatment in humans with reactive arthritis. Serum MMP-8 levels were reduced (mean +/- standard error of the mean, 678.9 +/- 185.6 versus 491.2 +/- 144.8 ng of MMP-8 per ml), but not statistically significantly. However, the reduction of salivary MMP-8 levels was statistically significant (3,729 +/- 1,905.3 versus 1,866 +/- 780.0 ng of MMP-8 per ml, P < 0.05). This study demonstrated that a 2-month regimen of doxycycline can reduce MMP-8 levels in serum and especially in body fluids (i.e., saliva) containing inflammatory exudates and thus may contribute to reduced tissue destruction.

Adult↗
PubMed1993

Collagenase and stromelysin in recurrent aphthous ulcers (RAU).

Six patients with recurrent aphthous ulcers were studied for the presence of matrix metalloproteinases (MMP) 1, 3, and 8 in the lesions and in the clinically unaffected control mucosa obtained from the opposite side. MMP-type specific antisera were applied in the avidin-biotin-peroxidase complex staining method. Neutrophil-type collagenase (MMP-8) was found intracellularly in the connective tissue under the necrotized epithelium, and also laterally to the ulcer in association with the basement membrane. Fibroblast-type collagenase (MMP-1) and stromelysin (MMP-3) were found in the epithelial cells adjacent to the ulcerous lesion. They were found also in the endothelium of capillary blood vessels and postcapillary venules and also in some macrophage- and fibroblast-like mononuclear cells in the lamina propria laterally to the ulcer. A small number of MMP-1 and MMP-3 positive cells were noted in the control biopsies obtained from the clinically uninvolved control mucosa. These findings suggest regional differences in the distribution of the two main collagenases, implying distinct roles in tissue destruction and remodeling.

Adult↗
PubMed1993

Biocompatibility of polyethylene and host response to loosening of cementless total hip replacement.

A human lymphocyte culture protocol was used to identify the biocompatibility pattern of fine particulate ultra-high molecular weight polyethylene. Polyethylene did not cause an increase in lymphocyte DNA synthesis as assessed by the 3H-thymidine incorporation method on culture Days 1, 3, nor 5. As analyzed with monoclonal activation markers, the polyethylene dependent expression of major histocompatibility complex (MHC) class II antigen as well as interleukin-2 receptor (CD25) was virtually nonexistent. An apparent increase in the amount of CD11b positive monocytes/macrophages from 7% +/- 2% to 22% +/- 6% was recorded. Samples of pseudocapsules of the totally replaced hips (THR) obtained at revision operations for aseptic loosening of cementless prostheses with polyethylene lining of the acetabular component, were obtained from ten patients for immunopathologic studies. In seven cases the prostheses consisted of chromium-cobalt-molybdenum steel alloy and in three cases of titanium. Revisions were performed on average 4.6 years (range, 2.5-7) after insertion of the prostheses. The predominant cell in the lining cell layer of the periprosthetic cavity was in each case the CD11b, CD68, and nonspecific esterase positive but endogenous peroxidase-negative macrophage. Proline 4-hydroxylase positive fibroblasts dominated the stroma that was also inhabited by usually perivascular mononuclear cell infiltrations of mainly CD11b/CD68 phenotype with occasional CD4-positive cells. Only few mononuclear cells were activated CD25 positive T cells or CD19-positive B-lymphocytes. In titanium-based THRs, the cytoplasm of the macrophages contained a large number of small metallic particles, although this phenomenon was not seen in chromium-cobalt-molybdenum steel-based THRs. Fine particulate ultra-high molecular weight polyethylene is immunologically relatively insert. Nevertheless, it causes a clear foreign body type of phenomenon in vitro. The loosening of cementless acetabular components was associated with CD11b- and CD68-positive macrophage reaction in the pseudocapsular tissue. In any case, there is no clinical or experimental evidence to suggest that the use of cementless THR prostheses with polyethylene sockets would prevent an adverse biologic host response.

Adult↗
PubMed1993

Are total hip prostheses implanted with the use of methylmethacrylate biocompatible?

OBJECTIVES: The biocompatibility of total hip replacement prostheses and methylmethacrylate cement which is used for fixation of the prosthetic components has been subject to debate for three decades. METHODS: We have studied the host response to total hip replacement prostheses in a number of clinical and experimental investigations. RESULTS: Methylmethacrylate cement is immunologically relatively inert while it causes, in in vitro experiments and in vivo, a foreign body type of reaction. In cementless prostheses, the wear of polyethylene which is used for lining of the acetabular component causes a similar foreign body type of reaction. CONCLUSION: Ultimately, the total hip prosthesis cannot be made invisible to the host system. The host response can be controlled and reduced, but not eliminated by technical improvement and development of more biocompatible materials.

Biocompatible Materials↗
PubMed1993

Hyaluronate in total hip replacement.

We studied the composition of the fluid in joint cavity of the hip joint in primary osteoarthritis (OA) from samples obtained at primary total hip replacement (THR) operations (N = 21) and in the THR pseudojoint, where the samples were obtained in revision operations for the common type of prosthesis loosening (N = 17). Protein concentrations differed little in both groups (31.8 +/- 1.9 mg/ml vs 34.4 +/- 1.9 mg/ml, p < 0.01), which suggests similar transcapillary flow in the degenerative hip joint and THR pseudojoint. Hyaluronate was found in OA joint fluid and in the fluid from the THR pseudojoint (2.21 +/- 0.23 mg/ml vs 0.43 +/- 0.04 mg/ml, p < 0.005) and high performance liquid chromatography (HPLC) analysis, calibrated using laser light scatter analyzed molecular weight standards, disclosed the low molecular weight nature of the OA synovial fluid compared to the THR pseudojoint fluid (1.12 +/- 0.84 x 10(6) vs 2.63 +/- 1.13 x 10(6) Da, NS). This suggests that THR arthroplasties cause an adaptive tissue response and formation of fibroblast-like B type lining cells able to synthesize and secrete hyaluronate.

Hip Prosthesis↗
PubMed1992

Inflammation of the subacromial bursa in chronic shoulder pain.

Subacromial bursal tissue was studied in 12 patients operated on for painful (10 patients with constant pain and 2 patients with pain on motion) rotator cuff tendinitis/impingement syndrome. The Neer acromioplasty technique was used. Six patients had moderate inflammatory changes and one had a slight inflammation. In three of the five remaining patients, the subacromial bursa did not show any signs of inflammatory involvement, but patients experienced pain at rest and at night, reflecting clinical inflammation in tissues other than the bursa. The two patients with pain only on strain did not show inflammation of the bursa. Immunohistochemical typing of the bursal tissue disclosed a typical chronic mononuclear cell infiltrate consisting mainly of CD2-positive T lymphocytes (50-80% of all inflammatory cells), accompanied by less frequent CD11b (C3bi receptor)-positive monocyte/macrophages (10-40%). The relative paucity of plasmablasts/plasma cells expressing PCA-1 suggests this to be an inflammatory rather than an immune response. Active involvement of some of the local cells is suggested to be the source of algogenic and hyperalgesic substances contributing to pain in chronic shoulder pain syndromes.

Acromion↗
PubMed1992

Immunoreactive neuropeptide nerves in ligamentous tissue in chronic shoulder pain.

Coracoacromial ligament and periligamentous fatty and loose connective tissue obtained during Neer's acromioplasty in patients with chronic painful rotator cuff tendinitis/impingement syndrome was studied for possible signs of inflammatory involvement and for the presence of neuropeptide-containing nerves, using routine histology and immunoperoxidase staining. No accumulations of inflammatory cells were found in the tissues studied. The dense ligamentous tissue proper was practically aneural, as was seen in staining for the generalized neuronal markers protein gene product 9.5 and synaptophysin. In contrast, the periligamentous fatty and loose connective tissue was innervated. Almost all nerves in such tissue contained C-flanking peptide of neuropeptide Y, whereas substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide-containing nerves were not found at all or were extremely rare. This suggests that the coracoacromial ligament is not a target of irritative inflammation. In the periligamentary sheath, nerves containing markers for the C-type nociceptive pain fibers were practically absent and all local nerves were postganglionic sympathetic vaso-regulatory nerves.

Adult↗