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Biomedical subjects

B Baslund

Publications and source records attributed to B Baslund.

At least 19 recordsLinked to original sources
PubMed2005

Magnetic resonance imaging for accelerated assessment of drug effect and prediction of subsequent radiographic progression in rheumatoid arthritis: a study of patients receiving combined anakinra and methotrexate treatment.

OBJECTIVES: By MRI to assess the efficacy of addition of anakinra for controlling synovitis and stopping erosive progression in patients with clinically active RA despite receiving methotrexate, and to determine the predictive value of MRI for subsequent radiographic erosive progression. METHODS: 100 mg anakinra subcutaneously/day was added to the treatment of 17 patients with clinically active RA despite methotrexate. MRI of the non-dominant wrist and 2nd-5th MCP joints (OMERACT evaluation) was performed at weeks 0, 12, and 36, and radiography of both hands and wrists (modified Sharp evaluation) at weeks 0 and 36. RESULTS: MRI synovitis scores were not significantly changed. Radiography of both hands and wrists after 36 weeks showed erosive progression in 11 patients, and MRI after 12 weeks in 10 patients. Nine of 10 patients with MRI progression at 12 weeks had radiographic progression at 36 weeks. Baseline MRI synovitis and erosion scores, but no clinical/biochemical parameters, correlated significantly with subsequent erosive progression. CONCLUSION: Addition of anakinra did not significantly reduce MRI signs of synovitis, and most patients had progressive joint destruction. Baseline MRI findings predicted subsequent radiographic erosive progression. Unilateral wrist and MCP joint MRI after 12 weeks had a similar sensitivity for detection of erosive progression as bilateral hand and wrist radiography after 36 weeks.

Adult↗
PubMed2002

No evidence of parvovirus B19, Chlamydia pneumoniae or human herpes virus infection in temporal artery biopsies in patients with giant cell arteritis.

OBJECTIVES: Recent studies have suggested that infective agents may be involved in the pathogenesis of giant cell arteritis (GCA), in particular Chlamydia pneumoniae and parvovirus B19. We investigated temporal arteries from patients with GCA for these infections as well as human herpes viruses using the polymerase chain reaction (PCR). METHODS: Thirty temporal artery biopsies from 30 patients suspected of having GCA within a period of 1 yr were examined. Thirteen patients had classical GCA, two had biopsy-negative GCA, 10 patients had polymyalgia rheumatica and five patients had other conditions. DNA was extracted from frozen biopsies and PCR was used to amplify genes from Chlamydia pneumoniae, parvovirus B19 and each of the eight human herpes viruses: herpes simplex viruses HSV-1 and 2, Epstein-Barr virus, cytomegalovirus, varicella zoster virus and human herpes viruses HHV-6, -7 and -8. RESULTS: In all 30 biopsies, PCR was negative for DNAs of parvovirus B19, each of the eight human herpes viruses and C. pneumoniae. CONCLUSIONS: We found no evidence of DNA from parvovirus B19, human herpes virus or C. pneumoniae in any of the temporal arteries. These agents do not seem to play a unique or dominant role in the pathogenesis of GCA.

Biopsy↗
PubMed1999

YKL-40 in giant cells and macrophages from patients with giant cell arteritis.

OBJECTIVE: YKL-40, a mammalian member of the family 18 glycosyl hydrolases, is secreted by activated macrophages at a late stage of differentiation. Macrophages are present in inflammation of the arterial wall and are thought to participate in the pathogenesis of giant cell arteritis (GCA). The aim of this study was to evaluate whether macrophages and giant cells of patients with GCA produce YKL-40, and whether serum YKL-40 concentrations are elevated in these patients. METHODS: Serum YKL-40 was determined by radioimmunoassay in 19 patients with GCA and 8 patients with polymyalgia rheumatica (PMR) who were followed up prospectively during 1 year of treatment with prednisolone. Immunohistochemical staining for YKL-40 was performed in temporal artery biopsy samples that were obtained before treatment. RESULTS: In the arteritic vessels of patients with GCA, positive staining for the YKL-40 antigen was found in CD68+ giant cells and mononuclear cells located in the media. Macrophages located in the adventitia and intima were negative for YKL-40. At the time of diagnosis, patients with GCA had an increased median serum level of YKL-40 (256 microg/liter; P<0.01) compared with healthy age-matched controls (median 118 microg/liter), and the serum level of YKL-40 decreased to normal levels during prednisolone treatment (-38% after 1 month; P<0.001). Most patients with PMR had normal serum YKL-40 levels (median 158 microg/liter) and had no changes in the serum YKL-40 levels during prednisolone treatment. The observed changes in serum YKL-40 did not always parallel the changes in serum C-reactive protein levels and erythrocyte sedimentation rate during the 1-year study period. CONCLUSION: YKL-40 is found in CD68+ giant cells and mononuclear cells in the media of arteritic vessels of patients with GCA, and the concentration of serum YKL-40 may reflect the local activity of these cells in the inflamed artery.

Adipokines↗
PubMed1998

Clinical evaluation of a capture ELISA for detection of proteinase-3 antineutrophil cytoplasmic antibody.

Detection of antineutrophil cytoplasmic antibodies (ANCA) has become a useful tool in the diagnosis of Wegener's granulomatosis and microscopic polyangiitis. However, the results obtained with indirect immunofluorescence (IIF) and by ELISA for ANCA demonstration do not always correlate. A possible explanation for this finding could be that proteins are denatured during the process of antigen purification or during coating onto the solid phase. To avoid this possibility, a monoclonal antibody to PR3 that is precoated on the plate can be used. In the present study we have used the monoclonal antibody (MoAb) 4A3 for the capture of PR3 in an ELISA, and a clinical evaluation of the diagnostic properties of the new capture ELISA has been made. The sensitivity of the capture PR3-ANCA ELISA was 85% in a material of c-ANCA positive sera. A specificity of 90% was obtained in analyses from patients having various forms of glomerulonephritis. There was a significantly higher diagnostic sensitivity of the capture PR3-ANCA ELISA (85%) compared to c-ANCA by IIF (58%) in patients with Wegener's granulomatosis with renal involvement. Capture PR3-ANCA and direct ELISA for MPO-ANCA together gave a diagnostic sensitivity of 98%, versus 75% using IIF. In conclusion, the capture PR3-ANCA ELISA seems to be a valuable tool in the diagnosis of Wegener's granulomatosis with renal involvement. Preliminary data suggest that the technique may have an advantage over direct ELISA for PR3-ANCA, as well as in the follow-up of c-/PR3-ANCA associated vasculitides. However, further prospective studies are needed to clarify this premise.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1998

Anti-neutrophil cytoplasm autoantibodies (ANCA). The need for specific and sensitive assays.

Anti-neutrophil cytoplasm antibodies (ANCA) are a group of autoantibodies primarily associated with systemic vasculitis. Hitherto, the method of choice for ANCA detection has been indirect immunofluorescence (IIF). By this method two major patterns can be seen: a cytoplasmic pattern (cANCA) or a perinuclear pattern (pANCA). The cANCA pattern is most often caused by antibodies directed against proteinase-3 (PR3) and in rare cases it is caused by anti-myeloperoixdase (MPO) antibodies. The pANCA pattern can de caused by antibodies directed against a large group of proteins i.e. MPO, lactofenin and bactericidal/permeability-increasing protein. Often there is a discrepancy between the results obtained by IIF and those reported from the use of assays with purified antigens. This causes confusion. Until now only anti-PR3 and anti-MPO have been found of any clinical value. Therefore, it would be more proper to use assays with these highly purified antigens instead of an unspecific method like IIF.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Complexes between proteinase 3, alpha 1-antitrypsin and proteinase 3 anti-neutrophil cytoplasm autoantibodies: a comparison between alpha 1-antitrypsin PiZ allele carriers and non-carriers with Wegener's granulomatosis.

To test the hypothesis that anti-neutrophil cytoplasm autoantibodies (ANCAs) interfere with the functions of proteinase 3 (PR3) (the Wegener autoantigen) and alpha 1-antitrypsin (alpha 1AT), complexes of PR3/alpha 1 AT and PR3/PR3-ANCA-IgG were assayed Plasma samples were obtained from 44 patients with Wegener's granulomatosis (WG): 34 had active disease (88% ANCA positive) whereas 10 patients were in remission (20% ANCA positive). Plasma samples from 14 of the patients with active disease were also available at the time of remission. The complexes of PR3/alpha 1 AT and PR3/PR3-ANCA-IgG were detected by capture enzyme-linked immunoassays (ELISAs) alpha 1 AT deficiency was evaluated by determining PiZ alleles by ELISA. Eight (18%) of the patients were PiZ positive. The frequency of this alpha 1-antitrypsin phenotype in the Scandinavian population is 4.7% (P < 0.001). The median PR3/alpha 1AT complex level in the PiZ-positive group with active disease (n = 5) was similar to the level in the PiZ-negative group with active disease. During remission the median level for the PR3/alpha 1AT complex was significantly higher than in the acute group (P < 0.001) including both PiZ-positive and PiZ-negative patients. No difference between PiZ positivity and PiZ negativity could be found in the remission group. PR3/PR3-ANCA-IgG complexes were found in patients with acute disease as well as in patients in remission, in almost equal frequency. This complex was also present in 13/18 ANCA-negative samples from patients in remission. Finally, purified IgG fractions from WG patients were examined for their capacity to inhibit binding between PR3 and alpha 1AT. An effect on the binding between PR3 and alpha 1AT by PR3-ANCA could not be demonstrated. Thus, our results do not support the hypothesis that PR3-ANCA interferes with the binding between PR3 and alpha 1AT. However, the high prevalence of the PiZ alleles among WG patients suggests that an imbalance between proteinases and alpha 1AT may be of importance in this disease. The clinical usefulness of both the PR3/alpha 1AT and the PR3/PR3-ANCA-IgG complexes and the possible influence on ANCA detection need to be examined in prospective longitudinal studies.

Acute Disease↗
PubMed1996

Anticardiolipin antibodies and lipoprotein (a) levels in patients with chronic renal failure treated with dialysis: associations with atherothrombotic disease.

The present study evaluated the importance of anticardiolipin antibodies (ACA) and lipoprotein (a) (Lp(a)) as markers of atherothrombotic disease in a retrospective study of patients on maintenance hemodialysis (HD) or peritoneal dialysis (PD). ACA and Lp(a) were measured in 22 patients on PD, and 64 on HD. Three patients were ACA IgM seropositive, whereas none were ACA IgG seropositive. The mean number of previous atherothrombotic events was 2.0 (1-3) in ACA seropositive patients, as compared to 0.7 (0-4) in ACA seronegative patients. The mean Lp(a) level was 56.7 mg/dl (3.0-217.7) in PD patients and 38.8 mg/dl (2.0-255.6) in HD patients (n.s.). Levels of Lp(a) greater than 30 mg/dl were not significantly associated with a history of atherothrombotic events, but all patients who had suffered a myocardial infarction or cerebrovascular insult had Lp(a) levels above 30 mg/dl. We conclude that ACA seropositivity is rare. All ACA seropositive patients had suffered atherothrombotic disease in the current study, whereas all patients with myocardial infarction or cerebrovascular insult had Lp(a) levels above 30 mg/dl.

Adult↗
PubMed1995

Clinical correlates and substrate specificities of antibodies exhibiting neutrophil nuclear reactivity--a methodological study.

In a serological laboratory with a routine service for determining autoantibodies to human neutrophils, antibodies giving a selective or preferential reaction with the nucleus or perinuclear area of neutrophils are not uncommon. The aim of this study was to look for clinical correlates with the presence of such neutrophil-reactive autoantibodies. The specificity of such antibodies for nuclear or cytoplasmic antigens was studied in 65 consecutive sera displaying nuclear/perinuclear reactivity at a titre of at least 80 using the indirect immunofluorescence technique (IIF) on ethanol-fixed leucocytes. The sera were also investigated by IIF on formalin-acetone fixed leucocytes and on HEp-2 cells. ELISA techniques were used to measure antibodies to azurophil granule constituents (ANCA), purified myeloperoxidase (MPO-ANCA), and lactoferrin (LF-ANCA). Furthermore a qualitative spot immunoassay was used for the detection of antibodies to alpha, beta, and gamma fractions, and the nuclear fraction of neutrophils, purified proteinase 3 (PR3), MPO, enolase, lysozyme, elastase, lactoferrin, and cathepsin G. The diagnoses linked to such GS-ANA/pANCA positivity were arthritides, vasculitides, inflammatory bowel disease and chronic hepatic conditions. MPO was the main antigen recognized in the vasculitis group, but apart from that, rather limited antigen reactivity was demonstrable by these techniques, lysozyme being the most frequently recognized autoantigen in patients with arthritides. Human lymphocytes served as a suitable control substrate when distinguishing between GS-ANA/pANCA and ANA, whereas HEp-2 cells usually could not be used if both classes of antibodies were present in a sample. Furthermore, formalin-acetone fixation is not recommended for routine use.

Antibody Specificity↗
PubMed1995

Vitamin D3 metabolism in patients with rheumatic diseases: low serum levels of 25-hydroxyvitamin D3 in patients with systemic lupus erythematosus.

1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) has been shown to modulate lymphocyte activation in vitro. Through binding to specific receptors 1,25-(OH)2 D3 inhibits proliferation, immunoglobulin production and the release of cytokines. Moreover, 1,25-(OH)2 D3 is efficiently produced by activated monocytes. These findings suggest that 1,25-(OH)2 D3 may play a role as a regulator of immunological activation. Consequently, we found it of interest to study the serum levels of the two major metabolites of vitamin D3 in patients with systemic lupus erythematosus (SLE) (n = 21), rheumatoid arthritis (RA) (n = 29) and osteoarthritis (n = 12). In patients with SLE the levels of 25-OH D3 were below those of the healthy controls (p = 0.0008) and OA (p = 0.0168). The levels 1,25-(OH)2 D3 corresponded to normal levels. There were no significant correlations between 25-OH D3 levels and clinical or paraclinical disease manifestations. Further, the phenotypic distribution of Gc-globulin, which binds vitamin D3 metabolites in circulation, was normal. The serum concentrations of 1,25-(OH)2 D3 and 25-OH D3 in patients with RA and OA corresponded to those of the controls. Although the cause of the reduced 25-OH D3 levels in SLE patients is unclear, possible beneficial effects of administration of vitamin D to these patients should be considered.

Adult↗
PubMed1995

Screening for anti-neutrophil cytoplasmic antibodies (ANCA): is indirect immunofluorescence the method of choice?

Detection of ANCA has become an important tool for the diagnosis and monitoring of disease activity in Wegener's granulomatosis (WG). Unfortunately, a group of sera positive by the standard method for ANCA detection, indirect immunofluorescence (IIF), are negative when more specific tests with purified proteins are used. In order to examine this discrepancy we examined groups of sera selected for being (i) C-ANCA-positive by IIF; (ii) positive in proteinase 3 (PR3)-ANCA ELISA; and (iii) from 24 patients with WG. The following assays were used: IIF, PR3-ANCA ELISA and capture PR3-ANCA ELISA using MoAbs against PR3. Furthermore, since granule enzymes are released during coagulation, we also measured ANCA in complex with PR3. To test if granule enzyme release had any influence on ANCA detection, both serum and EDTA-plasma were collected from a patient with active WG. No difference, however, was found. In the IIF-positive group (n = 60) 68% of the sera were positive in PR3-ANCA ELISA, 86% in capture PR3-ANCA ELISA and 80% were positive for the PR3/IgG-ANCA complex. In the PR3-ANCA ELISA group (n = 105) 88% of the sera were positive by IIF, 98% in capture PR3-ANCA ELISA and 53% in the PR3/IgG-ANCA assay. To evaluate the tests clinically sera from 24 patients with WG were examined. In the remission group (n = 10) two patients were positive by IIF, four in the PR3-ANCA ELISA, and five in the capture PR3-ANCA ELISA. Fourteen had active disease, and in this group 11/14 were positive by IIF, 10/14 in PR3-ANCA ELISA and 12/14 by capture-ELISA. The correlation between IIF and capture PR3-ANCA ELISA titre (r = 0.72, P = 0.0095) was better than between PR3-ANCA ELISA and IIF (r = 0.56, P = 0.043). It is concluded that the capture PR3-ANCA ELISA is more sensitive than PR3-ANCA ELISA, and that the capture ELISA can be used for screening of PR3-ANCA.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Measurements of proteinase 3 and its complexes with alpha 1-proteinase inhibitor and anti-neutrophil cytoplasm antibodies (ANCA) in plasma.

Wegener's granulomatosis (WG) is a systemic vasculitis which is diagnosed on clinicopathological findings. The diagnosis may be aided by the presence of anti-neutrophil cytoplasm antibodies (ANCA). In WG, ANCA are primarily directed to proteinase 3 (PR3), a serine protease of the azurophilic granules of the neutrophilic granulocyte. The main plasma inhibitor of PR3 is alpha 1-proteinase inhibitor (PI). To study if free PR3 or complexes between the enzyme and PI or PR3 and ANCA could be found in the plasma from patients with WG we have developed three ELISA systems for the detection of these complexes and free PR3. In all three assays monoclonal antibodies against PR3 were used as capture antibodies. After incubation with plasma, free PR3 was detected by affinity purified rabbit anti-PR3 followed by alkaline phosphatase-labelled swine anti-rabbit IgG. Serial dilutions of purified PR3 was used as standard. The detection limit was 3 ng/ml. PR3 complexed with PI was measured by rabbit anti-PI antibodies and alkaline phosphatase-labelled swine anti-rabbit IgG. Pre-formed in vitro complexes of PR3/PI in serial dilutions were used as standard. The detection limit of this assay was 1 ng/ml. PR3/IgG-ANCA complexes were detected by alkaline phosphatase labelled goat anti-human IgG. A positive plasma sample in serial dilutions was used as standard. Plasma samples from nine patients with WG, eight patients with fever of infectious origin without evidence of vasculitis and ten healthy donors were examined by these methods. Free PR3 could not be found in any of the plasma samples. PR3/PI complexes were detected in healthy donors at levels between 41-85 ng/ml. All WG patients, both active and inactive, had PR3/PI concentrations above this level, and so had all patients with fever. PR3/IgG-ANCA was found in three of the patients with WG, two being ANCA negative with inactive disease and one was ANCA positive with active disease. Thus, the developed methods can be useful for future studies of the clinical relevance of these complexes in patients with WG and possibly other vasculitides.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

A rapid and semi-quantitative method for the detection of autoantibodies by multiple spot immunoassay.

A method for rapid simultaneous determination of multiple autoantibodies in sera has been developed. 42 different antigens were coated onto a nitrocellulose membrane in a miniblotter apparatus with 42 lanes. The membrane was also coated with different concentrations of human IgG to create a standard curve. The blotting apparatus after coating, blocking and washing was turned 90 degrees so that all lanes crossed the antigen coated lanes. Thereafter, 42 sera were incubated with the antigens. After this stage the membrane was treated as in the usual dot-blot procedure. After incubation with alkaline phosphatase labelled anti-human IgG, staining and drying of the membrane, the staining intensity of individual lanes was scanned into a data file and analyzed by computer. By this method it was possible in 4 h to examine 42 sera for autoantibodies against 42 antigens, i.e., more than 1600 tests. Furthermore, the amount of antibody could be semi-quantified, using the IgG standards. The method should be useful for rapid screening of autoantibodies in a routine laboratory.

Antigens↗
PubMed1994

Some patients with anti-myeloperoxidase autoantibodies have a C-ANCA pattern.

Rapidly progressive glomerulonephritis with or without other signs of systemic vasculitis is often accompanied by antibodies to myeloperoxidase. Such antibodies normally produce a perinuclear pattern on ethanol-fixed neutrophils (perinuclear anti-neutrophil cytoplasm antibodies (P-ANCA)) at indirect immunofluorescence. We report here sera from three patients that are anti-myeloperoxidase-positive in ELISA that instead produce a cytoplasmic pattern (classical anti-neutrophil cytoplasmic antibodies (C-ANCA)), a pattern normally seen in conjunction with antibodies to proteinase 3. These sera did not react with proteinase 3. For two of the sera the specificity of the anti-myeloperoxidase reaction was confirmed with inhibition-ELISA experiments and with immunoblotting. A mouse anti-myeloperoxidase MoAb that produces a cytoplasmic pattern is also described. Competition ELISA experiments show that this antibody and anti-myeloperoxidase sera with cytoplasmic pattern recognize epitopes that are separate from epitopes recognized by another perinuclear pattern producing anti-myeloperoxidase MoAb. 'Cytoplasmic pattern' epitopes as well as 'perinuclear pattern' epitopes can be found on all three major myeloperoxidase isoforms, after separation by ion exchange chromatography. Affinity chromatography, using the cytoplasmic pattern producing anti-myeloperoxidase monoclonal antibody, shows that the epitope recognized by this MoAb is present on all myeloperoxidase molecules. This epitope is not confined to any special subpopulation. These findings indicate that all myeloperoxidase do not relocate after ethanol fixation, and that C-ANCA and P-ANCA epitopes exist simultaneously on the same myeloperoxidase molecule. We propose that the two immunofluorescence patterns arise due to different availabilities of the epitopes in the microenvironment where myeloperoxidase is present.

Aged↗
PubMed1993

Effect of 8 wk of bicycle training on the immune system of patients with rheumatoid arthritis.

The effect of 8 wk of progressive bicycle training on the immune system was evaluated in a controlled study on 18 patients with rheumatoid arthritis and moderate disease activity. Maximal O2 uptake increased significantly, whereas heart rate at stage 2 and rate of perceived exertion decreased significantly, in the training group compared with the controls. Resting levels of a number of immune parameters were measured before and after 4 and 8 wk of training. Training did not induce changes in blood mononuclear cell subpopulations, proliferative response, or natural killer cell activity. Furthermore the plasma concentrations of interleukin-1 alpha, interleukin-1 beta, and interleukin-6 did not change in response to training. It is concluded that 8 wk of bicycle training does not influence the immune system of patients with rheumatoid arthritis.

Aged↗
PubMed1993

Anti-cardiolipin antibodies (IgG and IgA) in women with recurrent fetal loss correlate to clinical and serological characteristics of SLE.

AIM OF STUDY: We investigated to which degree IgG, IgA and IgM anti-cardiolipin antibodies (aCL) are associated in recurrent abortion or late fetal death with other signs of autoimmune disease and in particular SLE. MATERIAL AND METHODS: Serological variables typical of SLE and of the anti-phospholipid antibody syndrome were measured once eight to 16 weeks after the last fetal loss in 158 women with recurrent abortion or late fetal death; women with manifest autoimmune rheumatic disease were excluded. RESULTS: (1) Positive values, i.e. above the 99th percentile of reference material, of IgG aCL and IgA aCL were observed in 4% and 7%, respectively, whereas 26% had positive values of IgM aCL. (2) IgG aCL and IgA aCL but not IgM aCL correlated to anti-nuclear antibodies and to anti-double stranded DNA. (3) Anti-double stranded DNA, IgG aCL and IgA aCL but not IgM aCL correlated to previous occurrence of thrombosis. (4) ANA correlated to lower blood platelet concentrations and higher erythrocyte sedimentation rates. CONCLUSIONS: Women with recurrent abortion or late fetal death who have higher but not necessarily abnormally high levels of IgG aCL or IgA aCL constitute a group with increased occurrence of clinical and serological characteristics of SLE. We suggest that these women be kept under surveillance for future development of autoimmune disease especially SLE. The women with high IgM aCL constitute another group without these characteristics.

Abortion, Habitual↗
PubMed1991

[Humero-scapular periarthrosis].

Humero-scapular periarthrosis (PH) is defined as an idiopathic painful condition in the shoulder with simultaneous limitation of active and passive movements in all directions. The condition is characterized by three phases: a painful period, a period dominated by stiffness and a period of recovery. PH is commonest between the ages of 40 and 60 years and the cumulated risk is estimated to be 2%. The incidence is higher in diabetics. The cause of PH is unknown and knowledge of the pathogenesis is very limited. Histological examination shows inflammation and fibrosis. Association with other pathological conditions of the upper limb or medical conditions, except diabetes mellitus, has not been documented with certainty. The average duration is 30 months but recovery without functional defects is common. Treatment is symptomatic and consists primarily of analgesics and rest during the painful phase. Local injections of steroids may be of effect. Exercises may be employed once the pain is under control and these have the object of improving mobility and increasing muscular strength.

Adult↗
PubMed1990

Frozen shoulder: current concepts.

The literature on frozen shoulder (FS) is reviewed. The etiology of FS is still not known and our understanding of the pathogenesis is limited. Studies on treatment programs under controlled conditions are few and incomplete. Further research is urgently needed.

Arthrography↗