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Biomedical subjects

T D Cooke

Publications and source records attributed to T D Cooke.

At least 91 records · Page 5Linked to original sources

The polyarticular features of osteoarthritis requiring hip and knee surgery.

A review of 62 operated cases with osteoarthritis (OA) indicated clinical evidence of polyarthritis in over 80%. In most cases features of generalized osteoarthritis (GOA) were found. Hand joint arthritis was prominent but, along with the other affected joints, usually asymptomatic. The coexistence of knee disease in cases with hip arthritis and the low incidence of hip changes in those with knee involvement suggest differences in cause for hip disease. These data indicate that the concept of OA as an oligoarticular lesion induced by mechanical or aging processes is inappropriate in a major proportion of knee and hip cases that present for joint replacement. They support the notion that an intrinsic tissue defect is involved in the etiopathogenesis of GOA.

Female↗

A quantitative method of assessing malalignment and joint space loss of the human knee.

Malalignment and joint space loss in the arthritic human knee can be measured quantitatively by employing a frame that allows for parallax correction of radiographs taken from the weight bearing lower limb. This standardized method will assist pre-operative planning for osteotomies and post-operative follow-up of patients with surgical re-aligned lower limbs. The procedure requires anatomically important points to be digitized, together with reference points built into the frame. Data are then processed automatically in a desk top computer, and the program provides for an easily understood diagram and listing of characteristic indices of malalignment.

Arthritis↗

Stimulation of collagenase secretion from rheumatoid synovial tissue by human collagen peptides.

Dayer et al. demonstrated that mononuclear cells from human peripheral blood produce a mononuclear-cell factor that stimulates collagenase secretion from adherent rheumatoid synovial cells. The production of this mononuclear-cell factor can be stimulated by phytohemagglutinin, a T-cell mitogen. We have examined immune mechanisms by which collagenase secretion may be stimulated from explants of rheumatoid synovial tissue and from primary monolayer cultures of rheumatoid synovial cells. Conditioned media from cultures of normal peripheral-blood mononuclear cells that had been activated by phytohemagglutinin stimulated collagenase secretion from most explants and from all monolayer cultures that were examined. The direct addition of phytohemagglutinin stimulated collagenase secretion in explants from eight of fourteen patients and in monolayer cultures from three of six patients. These observations indicate the presence of responsive T lymphocytes in rheumatoid synovial tissue and implicate them in the stimulation of collagenase secretion from synovial cells. The direct addition of type-II collagen peptides to rheumatoid explants also stimulated collagenase secretion in explants from six to fifteen patients. Four of five of these patients displayed moderate or severe disease activity. Other patients showed a marginal stimulation of collagenase secretion on addition of type-II collagen peptides (four of fifteen patients) and type-I collagen peptides (three of twelve patients). None of the patients with mild or inactive disease responded to type-II collagen. With one exception, the addition of collagen peptides to monolayer cultures did not stimulate collagenase secretion. An increased production of factors that enhance or inhibit the migration of polymorphonuclear leukocytes was also observed in explant cultures in response to the addition of phytohemagglutinin (in seven of twelve patients), of type-I collagen peptides (in five of ten patients), and of type-II collagen peptides (in five of eleven patients). There was no correlation between production of these factors and stimulation of collagenase secretion in rheumatoid synovial tissue.

Arthritis, Rheumatoid↗

Anatomic separation of the suprapatellar pouch spares its involvement by rheumatoid synovitis in the knee.

Synovectomy of the knee was performed in a 27-year-old female with seropositive rheumatoid arthritis of 6 years duration. At surgery the suprapatellar pouch was found to be separate from the rest of the knee joint, where direct access to articular collagenous tissues remained. The suprapatellar pouch, presumably separate from the knee cavity since birth, was free of disease. The rest of the joint lining, and synovium of the forefoot joints, that had been operated on at the same time, had gross and histological evidence of severe rheumatoid synovitis. The sparing of this suprapatellar pouch by rheumatoid disease is not easily explained, especially since its origin and nature are similar to other synovial parts of the knee that were actively involved. These latter areas had direct access to articular collagenous tissues. The findings of this case question the predilection of rheumatoid arthritis for synovium, and suggest that synovium and articular collagenous tissues are requisites of chronic rheumatoid arthritis.

Adult↗

The deposition of immunoglobulins and complement in osteoarthritic cartilage.

In a prospective study of 117 patients having reconstructive surgery for osteoarthritis, biopsies of hyaline articular cartilage and meniscal fibrocartilage were taken which exhibited immunofluorescence in their articular surfaces, for at least two immuno-globins (Ig) and beta 1c. These could represent immune complexes. The cases were classified into three Groups according to clinical, radiological and laboratory features, (1) non-arthritic -- 27 (3% positive); (2) secondary degenerative -- 32 (16% positive); (3) idiopathic osteoarthritic -- 89 (51% positive). The incidence of positive findings in Group III was significant at p less than 0.001 and less than 0.005 levels respectively as compared to those of Groups I and II. Our study of the disease features and their associated laboratory parameters indicated the following: positive findings correlated with an older mean age and longer disease duration. The gradings for mononuclear cell infiltration in synovial biopsies of Group III were more than two times higher than those of secondary arthritics. Group III also had an increased incidence of circulating auto-antibodies. A careful review of clinical features has not suggested a mixed population with rheumatoid disease but rather that Group III represents part of the spectrum of primary generalised osteoarthritis. These data suggest involvement of local immune mechanisms in cartilage degradation in the joints of those patients with longer term involvement.

Aged↗

Therapeutic experience with netilmicin.

Netilmicin, a new aminoglycoside antibiotic, was used to treat 19 patients with urinary tract infection and 5 with systemic infection. The causal organisms were Escherichia coli (in 2), Klebsiella pneumoniae (in 4), Serratia marcescens (in 12) and Pseudomonas aeruginosa (in 7); 1 patient was infected with two of these organisms. All the isolates of causal organisms except one of Serratia were initially sensitive to netilmicin but many were resistant to other aminoglycosides. Sixteen of the urinary tract infections responded to netilmicin therapy, although relapse occurred in three patients. Two of the three patients with musculoskeletal infection responded to combined therapy with surgery and netilmicin; the other patient responded to the same regimen but with carbenicillin added. Netilmicin cured pneumonia in one patient but failed in the other patient with pneumonia, who had leukemia. Superinfection occurred in five patients with urinary tract infection. Adverse reactions to netilmicin were minor. Netilmicin may prove to be a useful agent, particularly for infections due to multiresistant Klebsiella or Serratia, or when prolonged aminoglycoside therapy is required.

Adolescent↗

Electron microscopic morphology of immunoglobulin aggregates and their interactions in rheumatoid articular collagenous tissues.

Immunoelectron microscopy for IgG and IgA was combined with plain electron microscopy and light microscopy to study a variety of articular collagenous tissues from 14 cases of classic rheumatoid arthritis. Numerous extensive aggregates of IgG and IgA positive material were found widely spread in locations that coincided with immunofluorescent staining for these immunoglobulins and B1c. This Ig positive material is thought to represent deposits of immune complexes. As great and greater amounts were seen in fibrocartilage menisci as in hyaline cartilage. A single specimen of disease tendon was also positive. Severe pathologic changes of the matrix characterized by loss of normal morphology, alterations in collagen, and overall reduced density were observed in regions of aggregate deposition with a consistent replacement and disappearance of collagen in the locale of the aggregates themselves. Polymorphonuclear cells in regions of degraded hyaline and tendon matrix were seen to have phagocytosed aggregates. These data give some credence to a direct role of immune aggregates in rheumatoid arthritis articular collagenous tissues in disease pathogenesis.

Adult↗

The inflammatory role of immune complexes trapped in joint collagenous tissues.

The inflammatory role of immune complexes trapped in joint collagenous tissues has been investigated. Joint collagenous tissues obtained from rabbits with antigen-induced arthritis generated mediators of acute inflammation when incubated with fresh normal rabbit serum as a source of complement. The role of trapped immune complexes in chronic inflammation was also studied by the surgical insertion of menisci, obtained from arthritic and control joints, into the suprapatellar pouches of previously immunized or naive recipient animals. It was shown that when immune complex containing menisci were inserted into immune rabbits, a chronic inflammatory capsule developed around the donor tissue, reminiscent of the inflammatory pannus seen in rheumatoid cartilage. Normal menisci and immune complex containing menisci inserted in naive animals developed capsules rich in fibroplasts and collagen fibres. Since we have previously shown the presence of immune complexes in the great majority of joint collagenous tissues obtained from patients with rheumatoid arthritis, our results suggest that these complexes may play a role in the formation of pannus, which constitutes a major mechanism responsible for cartilage destruction.

Animals↗

The pathogenesis of chronic inflammation in experimental antigen-induced arthritis. II. Preferential localization of antigen-antibody complexes to collagenous tissues.

In an experimental arthritis induced by injection of bovine serum albumin or egg albumin into the joints of previously immunized animals, it has been demonstrated that the major portion of the radioactively labeled antigens injected was localized to avascular collagenous tissues in the joint, i.e., articular cartilage, menisci, and intra-articular ligaments. The antigens were partially eluted from the tissues with 5 M guanidine solution, but not with acid buffers or by 3 M magnesium chloride. The radioactive material eluted with guanidine was at least 80% precipitable by specific antisera. The radioactively labeled-inducing antigen was identified on the surface of articular collagenous tissues from arthritic joints by radioautography and immunofluorescence. Rabbit immunoglobulin and C3 were demonstrated in the same sites by immunofluorescence. The presence of specific antibody in collagenous tissues was demonstrated by the selective in vitro binding of (125)I-labeled-inducing antigen to menisci from arthritic joints of immunized animals. The evidence obtained indicates that in this model of chronic arthritis, the inducing antigen persists for long periods of time in the form of immune complexes in the surface layers of the intra-articular collagenous tissue. The antigen retained in this form may be responsible for the chronicity of the synovitis by serving as a direct stimulus for the maintenance of prolonged antibody synthesis in the synovium and by providing a source of complement-fixing antigen-antibody complexes for the mediation of joint inflammation.

Animals↗

Identification of immunoglobulins and complement in rheumatoid articular collagenous tissues.

Ninety-three patients with a variety of joint diseases were studied for evidence of immune complexes in articular collagenous tissues. Frozen sections of freshly obtained biopsies of hyaline articular cartilage and menisci were stained with fluoresceinated monospecific antisera for evidence of human immunoglobulins (IgG, IgM,IgA) and the beta1c component of complement. The criterion for the presence of complexes was the staining of two or more immunoglobulins and beta1c in an identical location of sequentially cut sections. Of the 42 patients with rheumatoid arthritis (RA) 83% were positive by this criterion. In those with classic RA the incidence was 92%. Sixteen patients with fresh joint trauma or nonarthritic disease had negative findings. Among 26 patients with noninflammatory disease, 4 of 8 with polyarthritis whose features suggested primary degeneration, 1 of 11 patients with secondary degenerative arthritis, and a single case of synovial osteochondromatosis had positive findings. Among 9 patients with miscellaneous inflammatory arthritides, all of 3 with psoriatic arthritis were negative; however 2 of 6 with other inflammatory arthritides were positive. The findings in classic RA suggest that immune complexes are deposited in the articular collagenous tissues. The persistence of these complexes may play a significant role in the chronicity of the synovitis.

Adolescent↗