Radiographic assessment of bony contributions to knee deformity.

Our recommendations for standing radiography of the lower limb are that assessments be standardized with respect to limb rotation and fixed relative positions of the hip, knee, and ankle. Specifically, a neutral knee rotation position should be set up, defined as alignment of the flexion plane straight ahead. For a complete appraisal, there should be both AP and lateral views in which the positioning of the patient is the same in all respects. The QPR frame greatly assists in achieving these objectives. Furthermore, the presence of a calibration system adds to the reliability and reproducibility of data by compensating for errors of position or alignment arising from the placement of the source and the film. Standardization of positioning also improves the detectability of axial-rotational deformities on comparison of AP and lateral views, providing more reliable indications of the need for CT than possible with nonstandardized short views. When a skyline patellar radiograph is added to the QPR routine, the end result is an excellent appraisal of lower limb alignment, providing a solid basis for diagnosis and planning of appropriate surgical remedies.

Mechanisms of cartilage degradation in inflammatory arthritis: interaction between chondrocytes and immunoglobulin G.

A possible role for immune complexes in the degradation of cartilage (rheumatoid arthritis and antigen induced arthritis) has been modelled in vitro by studying interactions between cultured bovine chondrocytes and monomeric (M) or heat aggregated (HA) IgG. Concentrations of IgG used were within the range of values reported in the synovial fluids of rheumatoid joints. ELISA and rosetting assays revealed Fc receptor mediated binding of MIgG and HAIgG to chondrocytes that had been cultured, but not to freshly isolated cells. Both forms of IgG stimulated the production of metalloprotease, but only HAIgG boosted generation of superoxide anion and reduced proteoglycan synthesis. HAIgG also stimulated cells to produce immunoreactive interleukin 1 although no biological activity was apparent. It is concluded that the equivalent behavior of chondrocytes in vivo, triggered by immune complexes, could contribute or lead directly to matrix degradation.

Toxicity of complement for chondrocytes. A possible source of cartilage degradation in inflammatory arthritis.

Cartilage from patients with rheumatoid arthritis and from animals with antigen-induced arthritis is frequently contaminated with complement-containing immune complexes. A possible role for complement activation in cartilage degradation was modeled in vitro by exposing cultured bovine chondrocytes to homologous serum, and determining cytotoxicity by monitoring the release of intracellular 51Cr. Complement activation was found to be cytotoxic, having maximal effect at 20-30% serum by 18 h. Serum toxicity was ablated by heat (50 degrees C, 20 min) or methylamine treatment but not by EGTA, suggesting that in these experiments activation occurred by the alternate route. The implications of the results are discussed in relation to ultrastructural evidence for the involvement of complement in the pathogenesis of cartilage degradation in inflammatory arthritis.

A quantitative approach to radiography of the lower limb. Principles and applications.

A method is described which provides standardised reproducible radiographic images of the lower limb. Anteroposterior and lateral radiographs are digitised and processed by computer to provide graphic/numeric displays of angles and linear measurements, relating the centre points of the hip, knee, and ankle. Two cases illustrate how surgical planning is facilitated when standardised data are available. These data confirm the close relationship between postoperative limb alignment and positioning of prosthetic elements.

Surgical implications of varus deformity of the knee with obliquity of joint surfaces.

Some arthritic knees with varus deformity show excessive valgus angulation of the femoral joint surface with proximal tibia vara. This causes a downward and medial inclination of the articular surfaces in the coronal plane. The patients we studied had a medial shift of the standing load-bearing axis, and arthritic changes mainly in the medial compartment. Some also had lateral tibial subluxation with twisting of the distal femur and proximal tibia in opposite directions. We assessed the articular geometry by precise radiographic analysis, and compared the results with those in normal volunteers and a group of osteoarthritic patients. The prevalence of this type of deformity in our osteoarthritic patients was 11.5%; its recognition allows the use of specific operative correction that may include double osteotomy or the precise orientation of prosthetic components.

Studies in the pathogenesis of rheumatoid arthritis. 1: Immunogenetic associations.

The critical role of CMI in the pathogenesis of RA has been reinforced, if not entirely illuminated, by recent information about the immunogenetic basis for individual susceptibility, in regard to genes of the HLA-D locus that control expression of MHC II determinants. An aberration in the T-cell response to cells presenting antigen is strongly implied, and must therefore be characterized. We will need to know what types of antigen trigger aberrant responses in those that are susceptible, and whether continuous presence of antigen is necessary to sustain chronic inflammation. The second part of this article will review immunological injury to joint tissues as an off-shoot of the CMI and HI responses of RA. Using data from animal models we shall examine criteria for establishing chronic joint inflammation, and consider their relevance to RA. We shall also consider the problem of why some joints are more susceptible than others to immunological injury.

Tibial anatomy and functional axes.

Articular geometry of the tibia has been studied in relation to the functional axis and extra-articular bone landmarks, using a Cartesian coordinate system. Thirty-one cadaver limbs were used, 26 of them paired. The donor age range was 61 to 89 years (17 females, 14 males), none of whom showed evidence of significant arthritic deterioration. Most linear parameters were greater in males than females (p less than 0.005), and correlations between these parameters were noted, e.g., tibial length versus plateau width (r = 0.7, p less than 0.01) with both genders combined. Gender differences occurred in only two of the angular parameters--tibial torsion (p less than 0.025) and foot rotation (p less than 0.005). For the latter, mean rotation was internal (-5 degrees) for males, and external (11 degrees) for females. No correlations between angular parameters were found. In the paired limbs, there was asymmetrical distribution of just two parameters--varus tilt of the tibial plateau margins (p less than 0.005) and lateral deviation of the tuberosity (p less than 0.025). The data complement a previous report on the femur. These studies are relevant to the kinematics of the lower limb, design and sizing of resurfacing components, and possibly to the pathogenesis of osteoarthritis.

Antigen-induced tenosynovitis in hypersensitized rabbits: a model for rheumatoid tenosynovitis.

Rabbits were first immunized and later challenged with the same antigen (bovine serum albumin, or ferritin) by injection into the tibialis anterior tendon. Inflammatory changes of the tenosynovium and epitenon included infiltration by neutrophils (early) and mononuclear cells (later) over a 6-week course of tenosynovitis. A pattern of antigen entrapment in the tendon together with immunoglobulin was shown by use of radiolabelled antigen and immunochemical staining. Half-life of antigen in the tissues averaged 5 days over the 6-week period. Changes in the epitenon included cellular necrosis, appearance of phagocytic cells, and disruption of the collagen matrix. Tissues of control animals (challenged without prior immunization) showed minimal changes and significantly less retention of antigen (P greater than 0.005). The model is relevant to the mechanism of tendon damage associated with antigen-driven chronic inflammation, as may be the case in rheumatoid arthritis.

Penetration of the outer membrane of Pseudomonas aeruginosa by synergistic combinations of beta-lactam and aminoglycoside antibiotics.

The mechanism of the synergistic action of carbenicillin-gentamicin and moxalactam-tobramycin combinations against Pseudomonas aeruginosa ATCC 9027 was investigated. Disruption of the outer membrane penetration barrier by EDTA treatment enhanced the activity of both combinations against the cells during growth for 100 min in exponential phase. However, there was no loss of the synergistic activity of the antibiotics as a result of this treatment. A procedure involving minimal inhibitory concentration testing in the presence of rifampin did not detect any destabilization of the outer membrane barrier by any of the four drugs over an 18-h period. The combined evidence indicates that beta-lactamaminoglycoside synergy is not mediated by the outer membrane of this organism.

Limited contribution of the outer-membrane penetration barrier towards intrinsic antibiotic resistance of Pseudomonas aeruginosa.

The role of the outer membrane (OM) was investigated in relation to the high level of intrinsic antibiotic resistance of Pseudomonas aeruginosa ATCC 9027. OM penetration barriers were measured by comparing turbidimetric growth curves of EDTA-treated and normal cells exposed to carbenicillin, moxalactam (LY 127935), gentamicin, tobramycin, rifampin, novobiocin, and vancomycin. OM barriers were also measured for carbenicillin and moxalactam in P. aeruginosa strain K 799/61, a hypersusceptible mutant presumed to have lost its penetration barrier in the cell envelope. Most antibiotics penetrated the OM efficiently and there was little difference between the two strains. The evidence therefore suggests that intrinsic resistance of P. aeruginosa, especially to the beta-lactam antibiotics, is not mainly due to the OM. A penetration barrier situated deeper within the cell envelope is hypothesized, the size of which in relation to any antibiotic may be estimated by comparing the IC50 values of EDTA-treated cells of the two strains.

Penetrability of the outer membrane of Neisseria gonorrhoeae in relation to acquired resistance to penicillin and other antibiotics.

Acquired antibiotic resistance in Neisseria gonorrhoeae is principally associated with three genetic markers, penA, mtr, and penB. penA is a specific marker for penicillin resistance, whereas mtr and penB are nonspecific in conferring resistance to penicillin and several other antibiotics as well. It has been suggested that the nonspecific markers may cause a general decrease in the penetrability of the gonococcal outer membrane. To investigate this, antibiotic penetration of the outer membrane was studied in two isogenic strains-FA19 (susceptible parent) and FA140 (containing penA, mtr, and penB)-and also in a clinical isolate with multiple resistance. The method involved brief treatment of exponential cells with ethylenediaminetetraacetic acid at 5 degrees C to disrupt the outer membrane barrier. The 50% inhibitory concentrations of antibiotics for treated and normal cells were measured turbidimetrically, and from their ratios outer membrane penetration barriers were calculated. Small barriers were observed for actinomycin D and benzylpenicillin, and these were very similar in the susceptible and resistant strains. Also, in FA140 no significant barriers for rifampin, erythromycin, and tetracycline were detected. These results suggest that mechanism(s) other than reduced outer membrane penetrability underlie acquired resistance due to penA, mtr, and penB.

Outer-membrane penetration barriers as components of intrinsic resistance to beta-lactam and other antibiotics in Escherichia coli K-12.

A new technique has been devised to investigate the penetration of antibiotics through the gram-negative outer membrane; the application here was to study intrinsic resistance of Escherichia coli K-12. Exponential cells in broth were briefly treated with 2.5 mM ethylenediaminetetraacetic acid at 5 degrees C to disrupt the outer membrane penetration barrier, and the response of treated and untreated cells to antibiotics was compared by turbidimetry. A barrier index was derived to describe the ability of 7 beta-lactam and 10 other antibiotics to penetrate the outer membrane of strain Y10. There was correlation between the molecular weight and log(10) barrier index (r = 0.59, P congruent with 0.01). The envelope mutant D22 (envA) had low barrier indexes for erythromycin, rifampin, ampicillin, and cloxacillin. For the beta-lactams, outer membrane penetration and affinity for inner membrane target site(s) triggering cell lysis were measured as independent components of the overall activity; although penetration and overall activity varied greatly, the affinities of most were within a narrow range.

Penicillin tolerance in Neisseria gonorrhoeae: evidence disallowing a penicillinase-mediated mechanism from a refined microbiological assay method.

A microbiological assay method has been developed and applied to Neisseria gonorrhoeae, for the purpose of detecting enzymatic deactivation of benzyl penicillin. Calibration of the method, using strains of Escherichia coli K-12 with previously reported penicillinase (EC 3.5.2.6.) activities, has shown that it is extremely sensitive and may be used in a quantitative manner. At the limit of sensitivity the test is able to detect penicillin breakdown in the order of 3 X 10(-3) mug in 48 h, which is equivalent to about 7 X 10(-8) mumol/min per milligram dry weight of cells. Over 100 strains of N. gonorrhoeae, most of them resistant to penicillin, were screened for their ability to deactivate penicillin during 48 h of growth in the presence of subinhibitory levels. No deactivation was detected. It is concluded, from quantitative evidence, that reduced penicillin sensitivity in N. gonorrhoeae is not due to the enzymatic deactivation of the antibiotic.