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Biomedical subjects

S M Horowitz

Publications and source records attributed to S M Horowitz.

31 records · Page 2Linked to original sources
PubMed1994

The interaction of the macrophage and the osteoblast in the pathophysiology of aseptic loosening of joint replacements.

Macrophage phagocytosis of cement particles with production of inflammatory mediators is a component of the underlying mechanism of aseptic loosening of joint prostheses. Prostaglandin E2 (PGE2), a bone resorbing mediator, has been implicated in the loosening process. Investigations have shown that macrophage phagocytosis of cement particles leads to production of bone-resorbing mediators other than PGE2. In this study, conditioned medium from macrophages exposed to crushed simplex cement particles stimulated osteoblasts to release radiolabeled arachidonic acid and metabolites. Incubation of osteoblasts in conditioned medium from macrophages exposed to cement particles small enough to be phagocytized increased PGE2 release 80-fold over unexposed osteoblasts (P < 0.001). Incubation of osteoblasts in conditioned medium from macrophages exposed to particles too large to be phagocytized, or to bone cement filtrate, did not stimulate PGE2 release. We propose that the role of the macrophage in aseptic loosening is primarily to recognize the mechanical failure of the cement mantle by phagocytosis of cement particles and subsequent production of small amounts of specific mediators. These mediators stimulate surrounding osteoblasts to secrete PGE2, which then amplifies the inflammatory response and ultimately results in bone resorption and aseptic loosening.

Arachidonic Acid↗
PubMed1993

Studies of the mechanism by which the mechanical failure of polymethylmethacrylate leads to bone resorption.

The purpose of this study was to examine the relationship between the mechanical failure of polymethylmethacrylate and bone resorption at the bone-cement interface of a prosthesis. Evaluation of tissue that had been retrieved from the cement-bone interface of eighteen femoral components of total hip prostheses that were loose without associated infection revealed that a critical factor associated with bone resorption was the presence of particles that were small enough (one to twelve micrometers) to be phagocytized by macrophages. To study this phenomenon in vitro, macrophages in tissue culture were exposed to three preparations of polymethylmethacrylate cement. A novel method of cement preparation was used with control for solid and soluble contaminants, which provided a sensitive and specific technique for the determination of which mediators were released from the macrophages. Electron microscopy demonstrated phagocytosis of particles of less than twelve micrometers in size, regardless of the type of cement preparation. Exposure to all three cement preparations resulted in toxicity, as reflected by inhibition of 3H-thymidine incorporation. Exposure also led to increased release of tumor necrosis factor, but none of the three preparations resulted in release of prostaglandin E2. Division of the cement preparations into two groups on the basis of the size of the particles demonstrated that exposure to particles that were small enough to be phagocytized led to inhibition of 3H-thymidine incorporation and release of tumor necrosis factor, while exposure to particles that were too large to be phagocytized did not. Neither exposure to small particles nor exposure to large particles of cement led to release of prostaglandin E2. Our results show that when the mechanical failure of cement produces particles that are small enough to be phagocytized, phagocytosis of the particles results in the increased production of tumor necrosis factor by the macrophages, which may in turn lead to bone resorption and prosthetic loosening. These small particles also decrease 3H-thymidine uptake by the macrophages.

Bone Cements↗
PubMed1993

Prosthetic and extremity survivorship after limb salvage for sarcoma. How long do the reconstructions last?

Ninety-three consecutive prosthetic reconstructions performed for limb salvage after the resection of sarcomas of the lower extremity were reviewed to determine how long the reconstructions lasted, how successful they were in avoiding amputation in the long term, how significant a problem was aseptic loosening, and what was the associated patient survival. Reconstruction was of the proximal femur in 16, distal femur in 61 and proximal tibia in 16 patients. Minimum follow-up time was 24 months, with a median of 66 months and mean of 80 months. If any event leading to the removal of the prosthesis is considered a reason for failure, the event-free prosthetic survival at five years for the proximal femur was 88%, distal femur 59%, and proximal tibia 54%. Limb survival at five years was significantly better, with the proximal femur at 88%, distal femur at 88%, and proximal tibia at 78% intact. Aseptic loosening survival was better than the event free prosthetic survival, which demonstrates the influence of factors such as sepsis (hematogenous) or wound necrosis that lead to prosthetic removal. Aseptic loosening survivorship of the proximal femur at five years was 100%; distal femur, 78%; and the proximal tibia, 73%. At five years, patient survival was low for the proximal femur (62%) and distal femur (75%) but notably better for the proximal tibia (93%). Prosthetic, extremity, and patient survival differed depending on the site. Wound necrosis was a significant cause of prosthetic removal and loss of limb early in this series, but the more aggressive use of soft tissue procedures has improved this.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1992

Soft-tissue management with prosthetic replacement for sarcomas around the knee.

The soft-tissue management was reviewed in 46 consecutive primary and nine revision segmental knee resections with prosthetic reconstruction performed for sarcomas around the knee. From January 1983 until August 1986, before the extensive use of free-tissue transfer in these patients, 20 primary segmental knee reconstructions were performed with five patients receiving gastrocnemius rotation flaps, and one patient receiving a late free flap (Group I). In this group, three patients were converted to an above-knee amputation because of wound problems. From August 1986 to August 1988, free-tissue transfer was available and extensively used in addition to rotation flaps to manage 26 primary (Group II) and nine revision (Group III) segmental knee reconstructions. In contrast to Group I, none of the patients in Groups II or III required amputation or conversion to a nonlimb-sparing procedure for soft-tissue management. None of the patients in this study received radiation therapy to their extremities. Chemotherapy protocols were similar in Groups I and II with 22 of 26 patients in Group I and 19 of 20 in Group II receiving treatment. The availability and expertise to perform free and rotational flaps at the time of initial excision provides greater selection and improved outcome for those patients whose wounds are closed primarily. The capability to perform free and rotation flaps at initial resection and for postoperative wound management is a major determinant of ultimate success in patients having reconstruction after excision of sarcomas about the knee.

Bone Neoplasms↗
PubMed1991

Macrophage exposure to polymethyl methacrylate leads to mediator release and injury.

To understand further the role of macrophages in the loosening of cemented arthroplasty, several in vitro effects of polymethyl methacrylate (PMMA) particle exposure in these cells were studied. The kinetics of arachidonic acid and derived inflammatory mediator release was characterized following macrophage exposure to either PMMA or control polystyrene particles. Temporal release of radiolabeled products by [14C]arachidonate-labeled cells was determined by sequential scintillation counting. Significant dose-dependent release of arachidonic acid mediators by macrophages was observed within half an hour of exposure to either PMMA or styrene particles. Unexposed control cells incubated in media alone did not release detectable amounts of radiolabeled products. The leakage of intracellular lactate dehydrogenase (LDH), a marker of cell injury, was detected spectrophotometrically 4 h following exposure to PMMA but not styrene. PMMA-induced LDH release was dose dependent. In contrast, polystyrene exposure failed to increase LDH release above unexposed control cells. These in vitro studies reveal that macrophages rapidly released arachidonic acid and derived inflammatory mediators in response to both PMMA and styrene particles. However, cells exposed to PMMA are lethally damaged, as reflected by the subsequent leakage of their intracellular LDH. We propose that a similar sequence of events may occur when macrophages encounter PMMA particles at the bone-cement interface. This is characteristic of a foreign body granulomatous response.

Animals↗
PubMed1991

Prosthetic arthroplasty of the knee after resection of a sarcoma in the proximal end of the tibia. A report of sixteen cases.

The results of a specific type of prosthetic reconstruction of the knee (total replacement arthroplasty) after resection of a sarcoma of the proximal part of the tibia in sixteen patients were retrospectively reviewed. The diagnosis was stage-IIB osteogenic sarcoma in nine patients, stage-IIB malignant fibrous histiocytoma in three patients, and stage-IB sarcoma of various types in four patients. The length of tibial resection ranged from 100 to 257 millimeters. Of the eleven patients who were available for functional examination (mean duration of follow-up, sixty-three months), three patients had an excellent result, seven had a good result, and one had a fair result. Of the five patients who were not available for functional testing, one who was doing well was lost to follow-up at eighty months, one had died of metastases at sixteen months, and three had had a secondary amputation for infection or for loosening of the prosthesis.

Adolescent↗
PubMed1988

Effects of polymethylmethacrylate exposure upon macrophages.

The effects of polymethylmethacrylate (PMMA) exposure upon macrophage viability and function were studied in an attempt to determine what role these cells play in the loosening of cemented arthroplasties. P388D1 murine macrophage cell line was exposed to PMMA and polystyrene particles of similar size and concentration. DNA synthesis following exposure to PMMA or polystyrene was studied by [3H]thymidine incorporation. Macrophage function was studied by analyzing the ability of activated macrophages to kill mast cell targets following particle exposure. Our results demonstrate that exposure of macrophages to PMMA particles in vitro inhibits DNA synthesis and impairs their cytotoxic ability. Histologic examination revealed that macrophages phagocytose both PMMA and styrene particles, but the former eventually lyse these cells. Our studies suggest that the histologic appearance of macrophages and foreign body giant cells at the bone-cement interface may be secondary to a repetitive cycle of PMMA particle phagocytosis and cell death, similar to that found in a foreign body granulomatous response.

Animals↗