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Biomedical subjects

J J Jacobs

Publications and source records attributed to J J Jacobs.

At least 73 records · Page 4Linked to original sources

Effects of particles on fibroblast proliferation and bone resorption in vitro.

An in vitro study was conducted to determine the ability of particle challenged human peripheral monocytes to modulate fibroblast proliferation and bone resorption. The effects of commercially pure titanium, titanium-aluminum-vanadium, and ultrahigh molecular weight polyethylene wear debris, either fabricated or retrieved from patients with failed total hip arthroplasties, were examined as a function of the composition, size, and dose of particles. In vitro generated particles were selected to be matched closely in particle size distribution to that found in vivo. Dosages were controlled by standardizing the ratio of particle surface area to mean monocyte surface area. The results support the hypothesis that, in vitro, challenge of monocytes by particulate wear debris results in a biphasic dose response. For the metal particles, fibrogenesis was observed over the range of 1x to 10x surface area ratio (the surface area of particles to the surface area of cells), although for metallic and polyethylene particles, saturated doses of 10x surface area ratio were required to stimulate bone resorption. In addition, metallic particles were able to stimulate fibrogenesis at doses at which simulated and retrieved polyethylene were ineffective. Although there may be a nonosteolytic chronically tolerable annual dose of ultrahigh molecular weight polyethylene wear debris corresponding to approximately 1x surface area ratio, lower doses, especially of metallic debris, may produce reactive fibroblast proliferation and fibroplasia that may contribute to implant loosening and failure.

Adult↗

Primary cementless acetabular reconstruction in patients younger than 50 years old. 7- to 11-year results.

The efficacy of primary cementless acetabular reconstruction in patients younger than 50 years of age was analyzed in 79 consecutive cementless, hemispheric, porous coated acetabular reconstructions (Harris-Galante-I). The average age was 37 years at surgery (range, 20-49 years). The average followup was 106 months (range, 78-126 months). No acetabular reconstructions were revised for aseptic loosening. Two stable acetabular reconstructions were revised during femoral revision. Two excessively worn polyethylene liners were exchanged and one acetabular osteolytic area was debrided and grafted; these procedures retained the metal shell. At final followup, all 72 acetabular reconstructions were radiographically stable. Acetabular osteolysis occurred in five cases (7.4%), from 84 to 104 months. Acetabular or femoral osteolysis occurred in patients with increased polyethylene wear. Polyethylene wear was inversely related to the patient's age. Using revision and loosening, the Kaplan-Meier 10 year survival of the acetabular reconstruction was 98.8% (95% confidence interval, 96.6%-100.%). The intermediate results of cementless, hemispheric, porous coated acetabular reconstruction in younger patients was excellent with no radiographic loosening. At 7- to 11-year followup, osteolysis was the most common problem and increased in frequency and extent with continued in vivo duration.

Adult↗

In vivo wear of Ti6A14V femoral heads: a retrieval study.

The surface characteristics of sixteen "monobloc" titanium-6% aluminum-4% vanadium (Ti6A14V) femoral components (two of the 6-Ti-28 type and 14 of the 6-Ti-32 type) retrieved after periods of 78-131 months following loosening of the femoral component, as well as two unimplanted controls, were studied. The femoral heads were examined by a combination of noncontact light profilometry, scanning electron microscopy, and energy-dispersive X-ray analysis. No consistent correlations were found between classical surface roughness parameters (average, root mean square, peak-to-valley roughness, and radius of curvature) and any clinical parameter studied (patient gender, weight, and height; primary diagnosis; implantation time; or calculated force applied on the hip joint). This extensive quantitative topographic analysis suggests that wear mechanisms in vivo are complex and that wear of titanium alloy femoral heads is partly attributed to a combination of an imperfect nature of the surface before implantation, removal of the oxide layer causing abrasion of the alloy, subsequent deformation of the bearing surface including polishing, and, to a very small degree, patient parameters.

Aged↗

Complications of a cable grip system.

From a group of 643 total hip arthroplasties, 98 patients required trochanteric osteotomies, and in 68 the trochanteric osteotomies were repaired with the Dall-Miles cable grip system (Howmedica, Rutherford, NJ). Trochanteric nonunion occurred in 17 of these patients (25%), with fraying and fragmentation of the cable present in 15 (88%). Of the 51 patients with radiographic union, 18 (35%) also had signs of fraying and fragmentation. Bone destruction around the cable in the area of the lesser trochanter was seen in seven patients (10%). Large deposits of metal debris at the inferior border of the acetabulum were seen in eight hips (12%). Multifilament cable did not appear to offer significant advantages over standard monofilament wire, and the potential problems of fraying, fragmentation, and free-floating metallic debris must be considered.

Adult↗

Cobalt and chromium concentrations in patients with metal on metal total hip replacements.

There has been a resurgence of interest in the use of metal on metal bearings in total hip arthroplasty. Although the use of metal on metal bearing couples would eliminate or substantially reduce particulate polyethylene generation (depending on the presence or absence of polyethylene in the implant system), there is concern about the potential for increased particulate and ionic metal generation in comparison with polyethylene on metal bearings. These metallic degradation products may be transported away from the implant site and distributed systemically. Chromium concentrations in the serum and urine and cobalt concentrations in the serum were measured in subjects with cobalt chromium alloy metal on metal total hip replacements and in controls without implants. Eight subjects with long term (> 20 years) McKee-Farrar total hip replacements had 9-fold elevations in serum chromium, 35-fold elevations in urine chromium, and at least 3-fold elevations in serum cobalt concentrations in comparison with controls. Six subjects with short term (< 2 years) metal on metal surface replacement arthroplasties had 3-fold elevations in serum chromium, 4-fold elevations in urine chromium, and 4-fold elevations in serum cobalt concentrations in comparison with subjects with McKee-Farrar implants. Although the toxicologic importance of these trace metal elevations has not been established, serum and urine metal concentrations may be useful markers for the tribologic performance of metal on metal bearings.

Adult↗

The bone-implant interface of femoral stems with non-circumferential porous coating.

UNLABELLED: A histological study was performed of the bone-implant interface of fifteen titanium-alloy femoral stems with porous coating limited to three proximal areas that did not cover the full circumference of the device. The specimens were obtained at autopsy from ten cadavera at a mean of forty-six months (range, one to eighty-nine months) after the implant had been inserted without acrylic cement. The volume fraction of bone within the porous spaces (the percentage of the porous space that was filled with bone) and the extent of bone ingrowth (the percentage of the porous-coated surface covered with in-grown bone that was more than one-half fiber-diameter deep, as measured from the outer surface of the porous coating), were determined with histomorphometric methods. Eleven of the fifteen stems had bone within the porous coating that was in continuity with the surrounding medullary bone. The mean volume fraction of bone ingrowth in these specimens was 26.9 per cent (range, 12.2 to 61.0 per cent), and the mean extent of bone ingrowth was 64.3 per cent (range, 28.6 to 95.2 per cent). Both of these parameters increased with time. In the other four stems, the bone lacked continuity with the surrounding trabecular bed. Two of these stems had a limited amount of bone within the porous coating, and two stems (from one patient) had no bone ingrowth. Periprosthetic membranes surrounded by a shell of trabecular bone covered the uncoated surfaces of the stems. The membranes of implants that had been in situ for eight months or more demonstrated polyethylene wear debris, and other particles generated at the level of the joint, within histiocytes throughout the length of the femoral stem. CLINICAL RELEVANCE: The findings in this study are relevant to the utilization and mechanisms of failure of femoral stems inserted without cement. Bone ingrowth and the resulting stability of the implant can be achieved with porous-coated stems. However, the extent of the surface that is porous-coated must be sufficient to prevent trabecular fracture as a secondary mechanism of loosening. Interruptions in the circumferential extent of the porous surface are associated with the formation of periprosthetic membranes, which provide a pathway for migration of particulate wear and corrosion products to the distal part of the stem. A circumferential coating may retard the access of particles and thus decrease the possibility of diaphyseal osteolysis.

Adult↗

Atypical clinical presentation of bileaflet cardiac prosthetic valve dysfunction. Preliminary report.

Single-leaflet disc immobilisation in 3 patients with St Jude Medical prostheses and 1 patient with a Carbo Medics valve prosthesis resulted in mild mitral regurgitation without acute pulmonary oedema. Three patients presented with slowly worsening pulmonary congestion while 1 patient had neurological symptoms. Clinicians need to be aware of the possibility of single-leaflet failure in a bileaflet cardiac valve prosthesis, because haemodynamic deterioration occurs insidiously in these patients, resulting in atypical symptoms and signs.

Adult↗

A single amino acid exchange, Arg-45 to Ala, generates an epidermal growth factor (EGF) mutant with high affinity for the chicken EGF receptor.

The finding that human epidermal growth factor (hEGF) and human transforming growth factor (hTGF) alpha bind with similar affinity to the human EGF receptor but differ in their affinity for the chicken EGF receptor was used as a model system to study ligand-receptor interaction of EGF receptor agonists. We previously constructed domain-exchange mutants of hEGF and hTGF alpha and found that the region COOH-terminal of the sixth cysteine residue in hTGF alpha is important for high affinity binding to the chicken EGF receptor (Kramer, R. H., Lenferink, A. E. G., Lammerts van Bueren-Koornneef, I., van der Meer, A., van de Poll, M. L. M., and van Zoelen, E. J. J. (1994) J. Biol. Chem. 269, 8708-8711). To analyze this domain in more detail, we now constructed four additional chimeras in which either the region between the sixth cysteine residue and the highly conserved Leu-47 was exchanged or the region COOH-terminal of Leu-47. A mutant in which the latter region in hEGF was replaced by hTGF alpha (designated E6ET) showed intermediate binding affinity, whereas replacement of the former region in hEGF by hTGF alpha was sufficient to generate a mutant (designated E6TE) with a similar high affinity for the chicken EGF receptor as wild type hTGF alpha. Furthermore, a deletion mutant of hEGF lacking three COOH-terminal amino acids, EGF50, showed intermediate binding affinity for the chicken EGF receptor similar to E6ET, but upon additional deletions (EGF49 and EGF48), this initial gain in affinity was lost. A systematic analysis of the region between the sixth cysteine residue and Leu-47 showed that the low affinity of hEGF for the chicken EGF receptor is mainly due to the presence of Arg-45. Replacement of the positively charged Arg-45 by Ala, the corresponding amino acid in hTGF alpha, was sufficient to generate a mutant growth factor with high affinity for the chicken EGF receptor. This indicates that in hEGF Arg-45 may play an important role in receptor binding. A model is proposed in which positively charged amino acids close to or within the receptor recognition site of hEGF prohibit high affinity binding to the chicken EGF receptor due to electrostatic repulsion of positively charged amino acids in the putative ligand binding domain of the chicken EGF receptor.

Amino Acid Sequence↗

The potential role of fibroblasts in periprosthetic osteolysis: fibroblast response to titanium particles.

Periprosthetic osteolysis with or without aseptic loosening is a major clinical problem in total hip arthroplasty. While the macrophage response to prosthetic wear debris and its role in periprosthetic osteolysis has been extensively studied, information regarding other cell types (fibroblasts, osteoblasts) is limited. This study explored the response of fibroblasts to particulate wear debris. Fibroblasts isolated from interfacial membranes of patients with failed total hip replacements and normal synovial tissue, when challenged with small-sized ( < 3 microns) titanium (Ti) particles, responded with significantly enhanced expressions of collagenase, stromelysin and, to a much lesser extent, their tissue inhibitor of metalloproteinases (TIMP). These "regulated" expressions at both mRNA and protein levels were correlated with the size and composition of particles. De novo protein synthesis was required for the regulation of these mRNAs. A similar effect could be induced by the treatment of the cells with particle-free conditioned medium from Ti particle-stimulated fibroblasts. Furthermore, this conditioned medium significantly suppressed the mRNA levels of procollagen alpha 1 (I) and alpha 1 (III) in osteoblast-like MG-63 cells. It is concluded that fibroblasts stimulated with certain particle debris may play an important role in periprosthetic osteolysis by releasing bone-resorbing metalloproteinases and mediator(s) which resulted in suppressed collagen synthesis in osteoblasts.

Base Sequence↗

Human monocyte response to particulate biomaterials generated in vivo and in vitro.

We studied the ability of four clinically relevant particle species to stimulate human peripheral blood monocytes to release bone-resorbing agents, including interleukin-1 (both interleukin-1 alpha and interleukin-1 beta), interleukin-6, and prostaglandin E2. The species studied were titanium-6% aluminum-4% vanadium (TiAlV), commercially pure titanium, fabricated ultrahigh molecular weight polyethylene, and polyethylene retrieved from interfacial membranes of failed uncemented total hip arthroplasties. For all species, the mean size was less than 1 micron. Human peripheral blood monocytes were challenged with these particles in a uniform manner on the basis of surface area. Phorbol 12-myristate acetate, zymosan, and nonphagocytosable titanium particles served as controls. Stimulation of human monocytes is a function of the composition and concentration of particles. In this study, TiAlV particles appeared to be the most competent to elicit the synthesis and release of inflammatory mediators. Particles of commercially pure titanium and of fabricated ultrahigh molecular weight polyethylene also could induce the release of various cellular mediators, albeit at a lower level, whereas the particles of polyethylene retrieved from interfacial membranes were less stimulatory in these short-term in vitro experiments.

Alloys↗

Bone ingrowth and wear debris in well-fixed cementless porous-coated tibial components removed from patients.

Bone ingrowth and the distribution of wear debris within the porous coating of 13 primary cementless porous-coated tibial components removed for reasons unrelated to fixation or infection were quantitatively described. The average length of implantation was 15.3 months (range, 3-30 months). The implants were all of the same design, made for Ti6A14V with a commercially pure titanium fiber-metal porous coating, which covered the undersurface of the tray and the four fixation pegs. In all but one component, supplemental screw fixation was used. The average extent of bone ingrowth within the tray was 27.1 +/- 16.1%, and the average volume fraction was 9.5 +/- 7.5%. There was significantly more bone ingrowth within the fixation pegs than within the tray and also more bone ingrowth in the anterior half of the tray than posteriorly. There was no correlation between the amount of bone ingrowth and the length of implantation, age, or sex of the patient; however, the depth and orientation of the resection plane were found to correlate with the topographic distribution of bone ingrowth. Particulate debris appeared to gain access to the interface via soft tissue pathways both at the periphery and through the holes for adjuvant screw fixation.

Alloys↗

Cellular mediators secreted by interfacial membranes obtained at revision total hip arthroplasty.

The interfacial membrane between implant and host-bone in aseptically loose total hip arthroplasties has a potential role in the etiology of local bone resorption and loosening of the prosthetic component. Inflammatory/potential "bone-resorbing" agents (cytokines/mediators) released by the cells of the interfacial membranes of loosened uncemented and cemented total hip arthroplasties were measured. Synovial tissues from patients with acute femoral neck fractures, patients with osteoarthritis, and cadavers without joint disorders were used as control subjects. Control synovial tissue from osteoarthritic patients secreted the highest levels of prostaglandin E2, interleukin-8, and tumor necrosis factor alpha. Interleukin-1 alpha was the only cytokine whose levels were elevated as much as 4-fold around uncemented implants compared with cemented implants, and up to 16-fold compared with control synovial tissue. An apparent inverse relation between interleukin-1 alpha and interleukin-6 interfacial membranes of total hip arthroplasties compared with control synovial tissues suggests a complex cellular mechanism through a cytokine/prostaglandin cascade; this may regulate the observed bone resorption in aseptic loosening.

Adult↗

Revision total hip arthroplasty without cement: subsidence of proximally porous-coated femoral components.

We prospectively studied the intermediate-term results of forty-nine revision total hip arthroplasties without cement that were performed because of aseptic loosening of a cemented femoral component in forty-five consecutive patients; the mean duration of follow-up was sixty-five months (range, forty-five to eighty-seven months). A curved, long-stem, titanium-alloy, non-circumferentially porous-coated femoral component was implanted in each hip. Preoperatively, a staging system was used to classify deficiencies of femoral bone stock according to the loss of cancellous or cortical bone in the metaphysis and diaphysis. Forty-one hips (84 per cent) had cortical or ectatic cavitary bone loss in the metaphysis. The mean Harris hip score significantly improved from 54 points preoperatively to 84 points at the time of the latest follow-up examination (p < 0.001). Twenty-seven patients (twenty-eight hips; 57 per cent) had at least two millimeters of subsidence of the femoral component during the first postoperative year. Eight patients (eight hips; 16 per cent) had no further progression of subsidence. Twenty-one patients (twenty-two hips; 45 per cent) had at least two millimeters of subsidence on two separate postoperative evaluations and therefore were considered to have progressive subsidence. Seventeen patients (nineteen hips; 39 per cent) had no measurable subsidence and were considered to have a stable femoral component. One of these seventeen patients had had a bilateral femoral revision and had progressive subsidence on one side. There was a positive trend for an association between subsidence and the degree of preoperative femoral bone deficiency (p = 0.10), but there was no association between subsidence and the fit of the prosthesis in the metaphysis and diaphysis or the fill of the canal of the femur (p > 0.50). There was no significant loss of bone in the hips with either a stable or a subsided femoral component (p > 0.50), and qualitative reconstitution of the cortex was noted in eleven (52 per cent) of the twenty-one most severely deficient (stage-III) femora. Survivorship analysis showed that, at seventy-two months, there was a 96 per cent chance of survival of the component (95 per cent confidence limits, 0.89 to 1.0) with revision as the end point but only a 37 per cent chance of survival (95 per cent confidence limits, 0.15 to 0.59) with revision or progressive subsidence as the end point.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Cements↗

Early failure of acetabular components inserted without cement after previous pelvic irradiation.

The effect of previous irradiation of the pelvis on the survival of acetabular components inserted without cement in primary total hip arthroplasty was examined. We searched a database of 1319 patients who had been managed with a primary total hip arthroplasty with insertion of a hemispherical porous-coated acetabular component without cement. This revealed twelve hips in eleven patients who had been managed with previous irradiation of the pelvis. Three patients had died after less than one year of follow-up, leaving eight patients with nine acetabular components available for study at an average of thirty-seven months (range, seventeen to seventy-eight months) after the operation. The type of radiation as well as the fractionation, dose, and portals were reviewed to determine the exposure of the periacetabular region to radiation. Failure of the component was assessed radiographically and clinically. At the time of follow-up, three of the nine acetabular components had migrated, as seen on radiographs, and had been associated with progressive radiolucency without clinical symptoms. Thus, four of the nine acetabular components failed, at an average of twenty-five months (range, sixteen to thirty-eight months). The other five components had not failed clinically and were stable radiographically at an average of thirty-six months (range, seventeen to sixty-three months). The insertion of acetabular components without cement in a previously irradiated pelvis has a high rate of failure. However, a superior method of acetabular reconstruction in this difficult situation has yet to emerge.

Acetabulum↗

Local and distant products from modularity.

In this study, the local and distant distribution of solid and soluble products of corrosion from the head and neck junction of modular femoral total hip prosthetic components were characterized. Particulate corrosion products from retrieved implants and surrounding tissues were analyzed. Serum transport and urinary excretion of metal was measured in correlation with the degree of corrosion at the head and neck junction. Particles of metal oxides, metal chlorides, and chromium phosphate corrosion products were identified on implants of 10 designs from 6 manufacturers. The most abundant solid corrosion product on the implant and within the periprosthetic tissues (size range, < 1-200 micrometers) was an amorphous chromium orthophosphate hydrate-rich material. Serum cobalt and urine chromium concentrations were elevated significantly in patients with implants that had moderate to severe corrosion in comparison with those with no to mild corrosion. Solid corrosion products from modular femoral stems may accelerate articular wear via a 3-body mechanism. Phagocytosable particles of these corrosion products may stimulate macrophage-mediated periprosthetic bone loss. Systemic dissemination of metallic corrosion products raises the issue of systemic toxicity; however, no overt evidence of metal toxicity was observed in this study.

Adult↗