Prostaglandin E2 production by the membrane surrounding loose and fixated cemented tibial hemiarthroplasties in the rabbit knee.

Sixteen mature New Zealand female rabbits had cemented, tibial hemiarthroplasty of the right knee (correction of hip) using a stemmed, fluted, titanium-alloyed, condylar type prosthesis. In the fixated prosthetic group (eight rabbits), a 1.5-cm3 doughy bolus of polymethylmethacrylate (PMMA) was used to cement the prosthesis firmly. In the loose group (eight rabbits), the cement was allowed to cure ex vivo on the implant; the prosthesis was then implanted and rotated to ensure that it was loose fitting. Roentgenograms performed postoperatively and at three months were graded for new lucent lines. The implant area was harvested aseptically and cultured during a three-day period, and the cumulative collection of tissue culture supernatants was assayed for prostaglandin E2 (PGE2). The mean cumulative grading of new lucent lines was 0.4 +/- 0.2 (mean +/- SEM) for the fixated prosthetic group and 2.3 +/- 0.5 for the loose prosthetic group. Specimens from the nonloose group produced 8.85 +/- 1.44 ng of PGE2 on the right prosthetic side, and 17.29 +/- 3.72 ng of PGE2 on the left, nonimplanted side. Specimens from the loose prosthesis group produced 52.35 +/- 16.28 ng of PGE2 on the right prosthetic side and 17.29 +/- 3.72 ng of PGE2 on the left, nonimplanted side. Increased PGE2 production relative to fixated prostheses was noted in the membranes surrounding loose prostheses. The left, nonimplanted sides were not statistically different. Roentgenographic and biochemical evidence indicates that a cemented tibial hemiarthroplasty implanted in the rabbit knee can provide a short-term model of arthroplasty loosening.

Suppression of prostaglandin E2 synthesis in the membrane surrounding particulate polymethylmethacrylate in the rabbit tibia.

Fifteen mature, New Zealand, female rabbits were divided into two groups. Using sterile technique, a 6-mm drill hole was made in the tibia 1 cm distal to the knee joint bilaterally. The marrow was scooped out underneath the hole. The right tibia received Simplex particulate cement polymer and the left leg functioned as a prepared, but nonimplanted, control. All animals were fed a standard diet. Whereas the six animals in Group 1 received regular water, the nine animals in Group 2 drank water in which sodium naproxen was dissolved (1.375 mg per ml). The animals were killed after 16 weeks. The implant area was harvested under sterile conditions and maintained in tissue culture. The cumulative collection of tissue culture supernatants over a three-day period was assayed for Prostaglandin E2 (PGE2) via radioimmunoassay. Specimens from Group 1 produced an average of 106.0 +/- 10.9 ng PGE2 on the right side, and 35.3 +/- 6.0 ng PGE2 on the left side. Specimens from Group 2 produced an average of 31.1 +/- 6.1 ng PGE2 on the right experimental side and 26.0 +/- 5.1 ng PGE2 on the left control side. The ratio of PGE2 values for the right divided by the left side yielded higher values in Group 1, compared to Group 2. Cement polymer particles have been shown to produce a florid foreign body histologic reaction similar to that associated with prosthetic loosening in man. This experiment has demonstrated that the increased PGE2 production by the membrane surrounding particulate cement polymer can be suppressed by the administration of an oral cyclo-oxygenase inhibitor. PGE2 has been previously shown to induce bone resorption in vivo and in vitro. The use of nonsteroidal antiinflammatory drugs may be indicated in retarding the bone loss associated with early prosthetic loosening.

Modulation of the membrane surrounding particulate cement and polyethylene in the rabbit tibia.

Twenty-nine mature New Zealand white, female rabbits were divided into four groups. Using sterile technique, a 6 mm drill hole was made in the tibia 1 cm distal to the knee joint. The marrow was scooped out underneath the hole. The right tibia received Simplex particulate cement polymer (PMMA) (groups 1 and 2) or polyethylene particles (UHMWP) (groups 3 and 4). The left leg functioned as a prepared but non-implanted control. All animals were fed a standard diet; those in groups 1 and 3 received plain water, while groups 2 and 4 drank water in which sodium naproxen was dissolved (1.375 mg/ml). Animals were killed after 16 wk. The implant area was harvested and grown in tissue culture. The cumulative collection of tissue culture supernatants over 3 d was assayed for prostaglandin E2 (PGE2) via radioimmunoassay. PGE2 production was significantly higher in the membrane harvested from the right side containing particulate cement with no sodium naproxen (group 1) compared with controls (P less than 0.05). The ratio of PGE2 values for the right divided by the left side yielded higher values in group 1, compared with groups 2, 3 or 4 (P less than 0.01). Previous studies have suggested that particulate debris and PGE2 production are associated with arthroplasty loosening. This experiment has demonstrated that PGE2 production by the membrane surrounding particulate debris can be suppressed by the administration of oral sodium naproxen. Because non-steroidal anti-inflammatory drugs are known to inhibit prostaglandin synthesis in man, these agents may prove useful in retarding the bone loss associated with early prosthetic loosening.

Prostaglandin E2 levels in the membrane surrounding bulk and particulate polymethylmethacrylate in the rabbit tibia. A preliminary study.

Fourteen mature New Zealand white female rabbits were allocated into two groups. Group 1 received a bolus doughy Simplex polymethylmethacrylate (PMMA) cement injected into the proximal tibia through a drill hole. Group 2 received an equal volume of particulate PMMA cement powder. The operated but nonimplanted left tibiae served as controls. The animals were killed after four months. The membrane surrounding the implant area was harvested aseptically and grown in tissue culture. The supernatants were assayed for prostaglandin E2 (PGE2) via radioimmunoassay. Bulk cement specimens produced on average 12.39 +/- 4.11 ng PGE2 on the right experimental side and 12.29 +/- 3.56 ng PGE2 on the left control side (not statistically different). Cement powder specimens produced 8.82 +/- 1.64 ng PGE2 on the right experimental side, which was statistically different from 4.21 +/- 0.88 ng PGE2 produced on the left control side. The ratio of PGE2 values for the right divided by the left side and the arithmetic difference between right and left sides were significantly higher in the particle group compared with the bulk group. Small, undigestable cement particles may be phagocytosed by foreign-body giant cells and histiocytes and then extruded into the extracellular compartment, along with substances such as PGE2. PGE2 has been implicated as the biologic mechanism for stimulating the bone lysis associated with prosthetic loosening.

A clinical-pathologic-biochemical study of the membrane surrounding loosened and nonloosened total hip arthroplasties.

The clinical and roentgenologic data from 31 excised components from 19 revision arthroplasty cases were correlated with the histology and biochemistry of the membrane at the bone-cement or bone-prosthesis interface. Twenty-seven components were cemented and four were uncemented. Twenty-four implants were clinically and roentgenologically loose, one was possibly loose, and six were well fixed. Loose components, whether cemented or not, demonstrated statistically higher prostaglandin E2 levels in the surrounding membrane compared to the nonloose group. Collagenase and M-collagenase levels were absent or insignificantly low in all specimens; no detectable interleukin 1 beta was found. This suggests that prostaglandin E2 may be associated with the bone lysis associated with prosthesis loosening.

Laser-induced autofluorescence of human arteries.

A new technique for imaging the intimal surface of arteries through optic fibers has been devised. With the aid of an optical multichannel analyzer, we recorded in real time fluorescence spectra during excitation of the arterial surface with an argon ion laser. Spectral parameters were used to detect atherosclerotic plaques and to discriminate normal tissue from lipid rich and calcified atheromas. By digitizing relative intensity values and the ratios of the peak at 550 nm to that at 520 nm into a gray scale, we generated pseudocolor maps of the arterial wall of 10 human aortas. Specific color distributions were congruent with the distribution of calcified tissue visualized by soft x-ray radiography and the distribution of lipid delineated by staining with Sudan IV. Thus, bidimensional maps obtained by laser spectroscopy can be used to identify the presence and composition of atherosclerotic lesions. Fluorescence imaging may prove to be an important application of laser techniques for the diagnosis and treatment of atherosclerosis.

Dissection of the mechanisms of immune injury in rheumatoid arthritis, using total lymphoid irradiation.

Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation. After radiotherapy, there was a marked decrease in the number and function of peripheral blood helper/inducer (Leu-3+) T lymphocytes, in the spontaneous secretion of interleukin-1 by synovial biopsy specimens, and in the activity of the joint disease. In contrast, levels of IgM, IgA, and IgG rheumatoid factors and C3 concentrations in blood and synovial fluid samples did not change significantly after therapy with total lymphoid irradiation.

Rapid visualization of proteins in isoelectric focusing gels: isolation of brain tubulin subspecies.

A method for visualization of unmodified proteins in polyacrylamide isoelectric focusing (IEF) gels is described. The proteins appear as white, translucent bands when disc IEF gels are placed in water. The gel can be scanned with a scanning spectrophotometer, or the protein bands can be excised using a simple apparatus, which is described, and the protein eluted. The method is fast, selective for proteins, sensitive, and quantitative. It has been used to isolate tubulin species separated by as little as 0.5 mm in disc IEF gels.

Brain tubulin microheterogeneity in the mouse during development and aging.

Mouse brain tubulin was analyzed on isoelectric focusing gels. High-resolution gels utilizing Bio-Rad ampholytes (pH 4--6) revealed 5--6 bands in the region corresponding to the alpha-subunit of tubulin and 10 or more for the beta-subunit. The same general banding pattern was observed regardless of the method of preparation of the tubulin. Two species prominent in the brains of immature mice, alpha 6 and beta 2, virtually disappeared during maturation, while species beta 6 to beta 10 appeared. No significant changes from the mature pattern were seen during aging (examined at 12, 23, and 30 months of age).

Selective associations of hormonal steroids with aminoacyl transfer RNAs and control of protein synthesis.

The hormonal steroids progesterone, estradiol, testosterone, and 5alpha-dihydrotestosterone bind to aminoacyl-tRNA, but not to deacylated tRNA, implying that a change in conformation of tRNA occurs on aminoacylation. Binding is restricted to a few tRNA species and depends on the structure of both tRNA and steroid. There is one binding site per aminoacyl-tRNA molecule, the specificity of which appears to depend on a restricted, single-stranded loop sequence and on the tRNA conformation. By binding to an aminoacyl-tRNA, a steroid can control polypeptide synthesis in a model in vitro system by inhibiting chain elongation under conditions where aminoacyl-tRNA concentration is rate-limiting.