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Biomedical subjects

L Dahlberg

Publications and source records attributed to L Dahlberg.

At least 37 records · Page 2Linked to original sources
PubMed1994

Intraarticular injections of hyaluronan in patients with cartilage abnormalities and knee pain. A one-year double-blind, placebo-controlled study.

OBJECTIVE: To compare the effect of intraarticular injections of hyaluronan and placebo (vehicle, saline) in patients with knee pain on exertion and with joint cartilage abnormalities. METHODS: Fifty-two patients with arthroscopically verified deep cartilage fissures and villus-like flakes in the symptomatic knee were randomly assigned to receive intraarticular injections of 2.5 ml of either hyaluronan or vehicle, weekly for 5 weeks. The effect was evaluated by both primary and secondary parameters of efficacy at 2, 4, 13, 26, and 52 weeks. RESULTS: At the followup visits, both groups had improvement from baseline; however, there was no difference between the groups in any of the relevant variables at any time point. CONCLUSION: The effects of intraarticular hyaluronan do not differ significantly from those of placebo in patients with knee pain and cartilage disease.

Adult↗
PubMed1994

Temporal patterns of stromelysin-1, tissue inhibitor, and proteoglycan fragments in human knee joint fluid after injury to the cruciate ligament or meniscus.

Stromelysin-1, tissue inhibitor of metalloproteinases-1 (TIMP-1), and proteoglycan fragments were quantified in knee synovial fluid samples in a cross-sectional study of patients who had injury to the anterior cruciate ligament or the meniscus. The average concentrations of stromelysin-1 and TIMP-1 increased 25-fold and 10-fold within the first day after the trauma, respectively, and the concentration of proteoglycan fragments increased 4-fold. From approximately 1-6 months after injury, the levels of these markers were higher after injury to the cruciate ligament than after injury to the meniscus. From 6 months to 18 years after trauma, however, the levels of stromelysin-1 and TIMP-1 in patients who had an injury to the ligament were the same as the levels in patients who had a meniscal lesion, but the levels were increased compared with those for a reference group of healthy volunteers. The molar balance of stromelysin-1 to TIMP-1 in synovial fluid in both groups of injured joints changed from a balance representing an excess of free inhibitor in the normal joint to one representing an excess of free enzyme in the injured joint. The increased release of these markers to joint fluid both early and late after trauma may be caused by a change in the loading patterns in the knee with an injured ligament or meniscus or by synovitis induced by bleeding. The increased release may be associated with the frequent development of posttraumatic osteoarthritis in patients with these injuries.

Adult↗
PubMed1994

A longitudinal study of cartilage matrix metabolism in patients with cruciate ligament rupture--synovial fluid concentrations of aggrecan fragments, stromelysin-1 and tissue inhibitor of metalloproteinase-1.

This is the first study which quantifies aggrecan fragments, stromelysin-1 and tissue inhibitor of metalloproteinases-1 (TIMP-1) in SF samples prospectively obtained from the same patient at different time intervals after a cruciate ligament injury of the knee. Aggrecan fragment concentrations were determined by dye precipitation with Alcian Blue. Stromelysin-1 and TIMP-1 were analysed by immunoassay. Ten healthy volunteers formed the reference group. Immediately after knee injury, all marker concentrations were higher as compared to the reference group. The high marker concentrations decreased gradually with time, and in samples obtained between 6 months and 6 years after the injury, median concentrations of some of the markers were not different compared to reference levels. This was in contrast to results from previous cross-sectional studies, where chronic phase median concentrations of all markers were consistently higher than reference levels. In previous cross-sectional studies, however, the samples were obtained at arthroscopy done because of knee complaints at different times after a knee injury. In the present study, the knee injured patients visited the orthopaedic outpatient ward only for SF sampling, and they had no or only minor knee symptoms. We conclude that the temporal changes of marker concentrations in joint fluid after knee injury, suggested from cross-sectional studies, have now been confirmed in a longitudinal, prospective cohort study. We further find that in patients with mild knee symptoms in the chronic phase after cruciate ligament injury, median SF levels of aggrecan fragments, stromelysin-1, and TIMP-1 are lower than in patients with significant knee complaints after the same type of injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Cartilage metabolism in the injured and uninjured knee of the same patient.

OBJECTIVE: To examine if unilateral knee injury affects the synovial fluid concentrations of aggrecan fragments, cartilage oligomeric matrix protein (COMP) fragments, stromelysin-1, and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the contralateral uninjured knee. METHODS: Synovial fluids from the injured and uninjured knees were obtained at different times in a group of patients after unilateral knee trauma. Serum samples were obtained on the same occasion. Concentrations of aggrecan fragments were determined by precipitation with Alcian Blue; those of COMP fragments, stromelysin-1, and TIMP-1 were measured by immunoassay. Concentrations were compared with those in a reference group of 10 healthy volunteers. RESULTS: Immediately after knee injury, concentrations of aggrecan fragments, COMP fragments, stromelysin-1 and TIMP-1 were increased in the synovial fluid of the injured knee. However, concentrations of aggrecan and COMP fragments, and stromelysin-1 increased also in the contralateral uninjured knee immediately after injury, but less than in the injured knee. Subsequently, the concentrations of all markers decreased in the synovial fluid of the injured knee, but remained unchanged in the uninjured knee. The concentration of aggrecan fragments in the injured knee decreased to less than that in the uninjured knee in the chronic phase. Serum concentrations of COMP were much smaller than those in synovial fluid. CONCLUSIONS: The increased concentrations of aggrecan and COMP fragments and stromelysin-1 in the joint fluid of the contralateral, uninjured knee following unilateral knee injury, compared with concentrations in healthy reference knees, suggest changes in joint cartilage metabolism in both knees following unilateral knee injury. The mechanisms for these changes are unclear. The low serum concentration of COMP makes it less likely that there is any significant 'exchange' of molecular makers between the knees. A further consequence of these findings is that the contralateral knee cannot be recommended as the only control joint in studies of matrix metabolism in patients with unilateral knee injury.

Adult↗
PubMed1994

On bias.

We performed a search in Medline to assess the quality of clinical journals in orthopedics from the point of view of study design. 3 levels of quality were chosen: prospective studies, random allocation or double-blind methods and randomized controlled trials; all entries were Medical Subject Headings (MeSH). Out of 25,538 articles indexed in Medline since 1966-1993 in the 8 most cited general orthopedic journals, 994 were indexed as prospective studies, while 138 were indexed as randomized, controlled trials. In recent years the number of well-designed articles has increased, as has the percentage. In a random check of 208 articles, approximately half were of a clinical type where these issues can be addressed. The agreement between the manual check and Medline indexing was good, but not perfect. It was concluded that the retrospective study representing clinical production control accounts for the vast majority of all published clinical articles in orthopedics. In recent years, a sharp increase in controlled trials had, however, occurred.

Double-Blind Method↗
PubMed1993

Candida albicans arthritis in a nonimmunocompromised patient. Complication of placebo intraarticular injections.

A nonimmunocompromised 32-year-old man with arthrosis of the knee participated as a placebo control in a clinical trial of intraarticular injections of hyaluronan. After the fourth weekly injection of saline, he developed a warm and swollen knee, and synovial fluid cultures revealed growth of Candida albicans. Oral fluconazole treatment was instituted 2 weeks after onset of symptoms, but failed to eradicate the infection. The patient recovered after treatment with local and systemic amphotericin B, systemic 5-fluorocytosine and surgical synovectomy. Quantitation of joint cartilage proteoglycan fragments in synovial fluid indicated extensive breakdown of cartilage during the acute phase of arthritis but, parallel to clinical recovery, these levels returned to normal.

Adult↗
PubMed1993

Stromelysin, tissue inhibitor of metalloproteinases and proteoglycan fragments in human knee joint fluid after injury.

OBJECTIVE: To determine in a cross sectional study the concentrations of stromelysin, tissue inhibitor of metalloproteinases (TIMP), and proteoglycan fragments in knee synovial fluid (SF) at different times after injury to cruciate ligament or meniscus. METHODS: Joint fluid samples were obtained from patients with knee injury diagnosed by arthroscopy. Concentrations of stromelysin-1 and TIMP-1 were determined by immunoassay with monoclonal and polyclonal antibodies. Cartilage proteoglycan fragments were quantified by immunoassay with polyclonal antibodies or by dye precipitation. RESULTS: Average concentrations of stromelysin increased 40-fold in association with injury, and after about 6 months decreased to a plateau level about 10-fold increased compared to a reference group with healthy knees. TIMP and proteoglycan levels also increased in similar temporal patterns, but less markedly. Increased average SF levels of these markers were maintained for at least 17 years after injury. SF from knees with injury contained a 1.5 to 2.5 molar excess of stromelysin over TIMP, while reference joint fluids contained a 2-fold molar excess of TIMP over stromelysin. CONCLUSION: The persistent changes in SF markers after joint injury may be associated with the cartilage destruction and frequent development of posttraumatic osteoarthritis in this group of patients.

Adult↗
PubMed1992

Cartilage matrix metabolism in osteoarthritis: markers in synovial fluid, serum, and urine.

Osteoarthritis is a major cause of disability and early retirement. Yet we lack the means to diagnose the disease in its early stages or to monitor the effects of treatment on the target tissue, the joint cartilage. Neither can we identify the disease mechanisms at the tissue or cell level. Current research focuses on the use of markers of cartilage matrix metabolism in body fluids as a means to diagnose and monitor osteoarthritis. Cartilage proteoglycan, collagen and glycoprotein fragments, as well as proteinases and their inhibitors, are being suggested for this purpose. Structural information on matrix molecule fragments released into body fluids may also help to identify the enzymes active in the destruction of the cartilage, a central issue in osteoarthritis.

Animals↗
PubMed1992

Proteoglycan fragments in joint fluid. Influence of arthrosis and inflammation.

We determined the concentration of proteoglycan fragments in knee joint fluid collected from knee-ligament injured patients more than 6 months after the trauma and from patients with acute pyrophosphate arthritis and arthrosis or with arthrosis only. Injured patients with normal or only mildly altered cartilage at arthroscopy and with normal radiographs, had twice the average concentration of healthy volunteers. Other injured patients with advanced, radiographic signs of arthrosis, had synovial fluid proteoglycan fragment concentrations within the range of healthy volunteers. Patients with pyrophosphate arthritis had the highest concentrations, substantially increased compared with both arthrosis patients, with or without knee injury and healthy volunteers. Likewise, there was an inverse relation between the degree of arthrosis and the concentration of proteoglycan fragments in the joint fluid in patients with pyrophosphate arthritis and arthrosis or with arthrosis only. We conclude that synovial fluid levels of proteoglycan fragments are influenced by the mass of cartilage matrix remaining in the joint, the inflammatory activity in the joint, and the metabolic activity of the cartilage cells.

Adult↗
PubMed1991

Demineralized allogeneic bone matrix for cartilage repair.

We tested the chondrogenic potential of demineralized allogeneic bone matrix (DABM) in the repair of osteochondral defects. In 42 adult rabbits, a 5-mm2 or 15-mm2 defect was created bilaterally in the intercondylar groove of distal femur. DABM was inserted directly in 37 defects, whereas in 35 it was inserted after previous placement in muscle for 4, 16, or 19 days. Another 12 defects were left empty, serving as controls. Subgroups of animals were killed at 6, 12, 18, and 26 weeks. The distal femora were excised and prepared for histologic evaluation in hematoxylin-eosin and toluidine blue. Cartilage-like repair tissue was observed in the majority of defects. However, there was a great variability in the experimental groups without any clear relationship to type of DABM implant, defect size, or postoperative time. Even individual knees exhibited varying stages of cartilage differentiation. Overall, DABM placed in muscle for 19 days appeared to yield the best repair of the defects. The most consistent findings of the present study were bone formation in the marrow of distal femur and, notably, the absence of bone differentiation toward the joint surface. Hence, it seems that the synovial environment prevents bone formation otherwise induced by DABM in vascular tissue. Although tissue formed in articular defects supplemented with DABM is of cartilaginous differentiation, which is retained over time, it is of highly variable quality. Hence, the described approach has to be optimized before it can be applied for the purpose suggested.

Animals↗
PubMed1990

The occurrence of neuropeptides at different stages of DBM-induced heterotopic bone formation.

In developing heterotopic bone in the rat, induced by allogeneic bone matrix, we immunohistochemically detected nerves containing substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and tyrosine hydroxylase (TH). After 10 days they were dicernible amidst differentiating chondroblastoid cells in fibrous tissue around and within the implants. Over the next 3 weeks, the nerves increased in number and gradually attained a shape and distribution resembling normal osseal nerves; varicose fibres frequently occurred in periosteum-like fibrous tissue and bone marrow adjacent to newly formed bone. At 8 weeks, NPY-fibres increased, particularly in the marrow and this abundance of NPY fibres remained at 16 weeks. VIP-immunoreactive fibres were only observed in the surrounding periosteum-like fibrous tissue 4-6 weeks after implantation. These observations, in combination with recent findings of receptors to neuropeptides on bone cells, suggest a neurogenic influence on physiological processes in bone tissue.

Animals↗
PubMed1989

Increased levels of proteoglycan fragments in knee joint fluid after injury.

We measured levels of cartilage proteoglycan (PG) fragments in knee joint synovial fluid obtained from patients with previous trauma of the knee, early gonarthrosis, or pyrophosphate synovitis, and in age-matched control subjects. During the initial 3-4 weeks after rupture of the anterior cruciate ligament or the meniscus (confirmed by arthroscopy), markedly increased PG fragment levels were found. At later times after trauma (up to 4 years), many of these patients still had significantly elevated levels of cartilage PG fragments in the joint fluid. In a group of older patients with gonarthrosis, these levels were only moderately elevated, while in patients with acute pseudogout, greatly increased levels were observed. Although longitudinal studies are needed to validate the significance, PG fragments in joint fluid may be a marker for early posttraumatic arthrosis.

Adolescent↗