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Biomedical subjects

P E Di Cesare

Publications and source records attributed to P E Di Cesare.

At least 19 recordsLinked to original sources

Cavitary acetabular defects treated with morselized cancellous bone graft and cementless cups.

The use of impacted morselized cancellous bone grafts in conjunction with cementless hemispherical acetabular cups for treatment of AAOS type II acetabular cavitary deficiencies was evaluated in a retrospective study of 23 primary and 24 revision total hip arthroplasties, at a mean follow-up of 7.9 and 8.1 years, respectively. All primary hips received autografts, while all revision hips received allografts. Modified Harris Hip Scores for primary and revision hip replacements increased from a pre-operative mean of 37 and 47 to a postoperative mean of 90 and 86, respectively. All 23 autografts and 23 out of 24 cancellous allografts were radiographically incorporated without evidence of resorption. There were no instances of infection, component migration, or cases requiring subsequent acetabular revision. We conclude that impacted morselized cancellous bone-graft augmentation of cementless cups is a viable surgical option for AAOS type II cavitary acetabular defects.

Acetabulum↗

COMP is selectively up-regulated in degenerating acinar cells in chronic pancreatitis and in chronic-pancreatitis-like lesions in pancreatic cancer.

BACKGROUND: Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized histomorphologically by progressive development of fibrosis and atrophy of the pancreatic parenchyma. Cartilage oligomeric matrix protein (COMP) is a member of the thrombospondin (TSP) family of extracellular glycoproteins that is expressed in CP tissues. In the present study, we characterized COMP mRNA and protein expression in the normal pancreas, chronic pancreatitis, and pancreatic cancer tissues. METHODS: 15 normal pancreatic tissues, 14 CP tissues and 14 pancreatic cancer tissues were analyzed by Northern blotting, Western blotting, in situ hybridization and immunohistochemistry. RESULTS: COMP mRNA and protein were detected at moderate to high levels in chronic pancreatitis tissues, at moderate levels in pancreatic cancer tissues, but at low levels in normal pancreatic tissues and in four pancreatic cancer cell lines. COMP mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells in CP tissues as well as in CP-like lesions in pancreatic cancer tissues. COMP protein was also present in the fibrotic tissue in CP. In contrast, COMP expression was weak to absent in the cytoplasm of cancer cells in pancreatic cancer tissues, and in ductal cells and islet cells in normal pancreatic tissues. CONCLUSION: COMP is preferentially expressed in degenerating acinar cells in CP and in CP-like areas in pancreatic cancer, suggesting a potential role of this gene in the course of acinar cell degeneration and dedifferentiation. COMP might thus serve as a marker for tissue destruction and disease activity in CP.

Adolescent↗

The relationship of the factor V Leiden mutation or the deletion-deletion polymorphism of the angiotensin converting enzyme to postoperative thromboembolic events following total joint arthroplasty.

BACKGROUND: Although all patients undergoing total joint arthroplasty are subjected to similar risk factors that predispose to thromboembolism, only a subset of patients develop this complication. The objective of this study was to determine whether a specific genetic profile is associated with a higher risk of developing a postoperative thromboembolic complication. Specifically, we examined if the Factor V Leiden (FVL) mutation or the deletion polymorphism of the angiotensin-converting enzyme (ACE) gene increased a patient's risk for postoperative thromboembolic events. The FVL mutation has been associated with an increased risk of idiopathic thromboembolism and the deletion polymorphism of the ACE gene has been associated with increased vascular tone, attenuated fibrinolysis and increased platelet aggregation. METHODS: The presence of these genetic profiles was determined for 38 patients who had a postoperative symptomatic pulmonary embolus or proximal deep venous thrombosis and 241 control patients without thrombosis using molecular biological techniques. RESULTS: The Factor V Leiden mutation was present in none of the 38 experimental patients and in 3% or 8 of the 241 controls (p = 0.26). Similarly there was no difference detected in the distribution of polymorphisms for the ACE gene with the deletion-deletion genotype present in 36% or 13 of the 38 experimental patients and in 31% or 74 of the 241 controls (p = 0.32). CONCLUSIONS: Our results suggest that neither of these potentially hypercoaguable states are associated with an increased risk of symptomatic thromboembolic events following total hip or knee arthroplasty in patients receiving pharmacological thromboprophylaxis.

Journal Article↗

The effect of alendronate (Fosamax) and implant surface on bone integration and remodeling in a canine model.

Patients at high risk for osteoporosis and its associated morbidity, including postmenopausal women, are being pharmacologically managed to stabilize and improve bone mass. Alendronate sodium (Fosamax) is a commonly used antiresorptive agent effective in osteopenic women for reducing bone resorption, increasing bone density, and decreasing fracture incidence. With the increased incidence of alendronate-treated women who are undergoing hip replacement or fracture repair by prosthesis placement, data are needed to predict how alendronate affects host bone integration with uncemented surfaces. The aim of this study was to determine the effect of alendronate on new bone formation and attachment to implant surfaces in a normal and simulated estrogen-deficient, calcium-deficient canine model, using an implantable bone growth chamber. Alendronate did not affect host bone integration to surfaces commonly used in uncemented total joint arthroplasty, but there were significant differences dependent solely on the type of surface.

Alendronate↗

Tissue distribution and measurement of cartilage oligomeric matrix protein in patients with magnetic resonance imaging-detected bone bruises after acute anterior cruciate ligament tears.

Histologic and immunostaining analyses were performed on articular cartilage/subchondral bone biopsy specimens overlying MRI-detected bone bruises in 12 patients with anterior cruciate ligament (ACL) tears. Staining with toluidine blue for proteoglycan revealed loss of staining from the superficial portion of the articular cartilage. Immunostaining for cartilage oligomeric matrix protein (COMP) showed an increased staining in the superficial matrix of the articular cartilage. Using polyclonal antisera against COMP, the authors performed a competitive enzyme-linked immunosorbent assay (ELISA) on the synovial fluid from the injured and uninjured knees. There was an approximately 10-fold higher synovial fluid COMP levels in injured knees. The COMP levels were greater in those patients who had synovial fluid samples harvested closer to the date of initial injury. Western blot analysis of the synovial fluid showed an increased presence of COMP degradation fragments from injured knees. These results are indicative of a significant injury to the articular cartilage, and may represent preclinical posttraumatic osteoarthritic lesions.

Adolescent↗

Efficacy of combined technetium-99m sulfur colloid/indium-111 leukocyte scans to detect infected total hip and knee arthroplasties.

The reliability of combined indium-111 leukocyte/technetium-99m sulfur colloid scans, with and without the addition of blood pooling and blood flow studies, in the diagnosis of infected total joint arthroplasty was investigated. Both scans were performed on 58 patients before reoperation of total hip or knee arthroplasty in the period 1996-1999. Results for imaging alone included 100% specificity, 46% sensitivity, 100% positive predictive value, 84% negative predictive value, and 88% accuracy. Inclusion of blood pooling and flow phase data improved results to 66% sensitivity, 89% negative predictive value, and 90% accuracy, with reductions in specificity (98%) and positive predictive value (91%). Routine use of these radionuclide scans is not supported by these data.

Adult↗

Midterm clinical and radiographic results with the genesis I total knee prosthesis.

The midterm results of primary posterior cruciate ligament-retaining, minimally conforming, cemented modular total knee arthroplasties using the Genesis I prosthesis in 110 knees in 72 patients were reviewed. Patients were evaluated at a mean follow-up of 7.3 years by Knee Society pain and functional scores, radiographic and survivorship analysis, and Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) health status questionnaire. Range of motion increased from an average of 96.3 degrees to 112.5 degrees. Knee Society pain and functional scores increased from preoperative averages of 55 and 44 to 92 and 88, respectively. There were 91 excellent, 16 good, 1 fair, and 2 poor results. WOMAC scores were increased significantly in each subcategory examined (pain, stiffness, and physical function). Kaplan-Meier survivorship was 97% at 10 years. An increase in loosening as a result of eccentric stress concentration secondary to the nonconforming design of this prosthesis, theoretically a matter of some clinical concern, was not shown in this investigation.

Aged↗

Orthopaedic manifestations of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown origin. It affects multiple organ systems, but most frequently the musculoskeletal system. Highly variable manifestations include small and large joint involvement, spinal involvement, periarticular tissue symptoms, and complications associated with chronic steroid use such as osteonecrosis, osteoporosis, and stress fractures. The following review summarizes the common orthopaedic manifestations of SLE.

Humans↗

Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP).

Matrix metalloproteinase (MMP)-19 and MMP-20 (enamelysin) are two recently discovered members of the MMP family. These enzymes are involved in the degradation of the various components of the extracellular matrix (ECM) during development, haemostasis and pathological conditions. Whereas MMP-19 mRNA is found widely expressed in body tissues, including the synovium of normal and rheumatoid arthritic patients, MMP-20 expression is restricted to the enamel organ. In this study we investigated the ability of MMP-19 and MMP-20 to cleave two of the macromolecules characterising the cartilage ECM, namely aggrecan and the cartilage oligomeric matrix protein (COMP). Both MMPs hydrolysed aggrecan efficiently at the well-described MMP cleavage site between residues Asn(341) and Phe(342), as shown by Western blotting using neo-epitope antibodies. Furthermore, the two enzymes cleaved COMP in a distinctive manner, generating a major proteolytic product of 60 kDa. Our results suggest that MMP-19 may participate in the degradation of aggrecan and COMP in arthritic disease, whereas MMP-20, due to its unique expression pattern, may primarily be involved in the turnover of these molecules during tooth development.

Aggrecans↗

Chondrocyte-specific enhancer regions in the COMP gene.

The molecular events governing the differentiation of mesenchymal cells into chondrocytes and the expression of cartilage marker genes are poorly understood. Cartilage oligomeric matrix protein is a noncollagenous extracellular matrix protein with a relatively cartilage-specific spatial and temporal expression pattern. To understand the mechanisms controlling chondrocyte-specific expression of cartilage oligomeric matrix protein, we cloned 1.9 kb of the 5' flanking promoter sequence of the murine cartilage oligomeric matrix protein gene and identified two spatially distant cartilage-specific enhancer regions by deletion analysis. One element is situated proximally (proximal positive element: -125 to -75) and a second region is located distally (distal positive region: -1925 to -592) relative to the transcription start site. Interestingly, nucleotides within the proximal positive element are conserved between the mouse and human promoters and resemble consensus sites for the binding of members of the high mobility group class of transcription factors. Defining cartilage-specific regulatory elements in the cartilage oligomeric matrix protein promoter may provide useful molecular probes for identifying transcription factors that control acquisition of the chondrocytic phenotype.

Animals↗

Molecular cloning, sequencing, and tissue and developmental expression of mouse cartilage oligomeric matrix protein (COMP).

Mouse cartilage oligomeric matrix protein cDNA was cloned and sequenced by a reverse transcription-polymerase chain reaction. The open reading frame encoded a product of 755 amino acids that shares a high degree of identity to and possesses all the characteristic molecular features of both rat and human cartilage oligomeric matrix protein. This suggests that cartilage oligomeric matrix protein is highly conserved during evolution. The clone was 83, 84, and 95% identical to human, bovine, and rat cartilage oligomeric matrix protein cDNA, respectively. In tissues from the adult mouse, cartilage oligomeric matrix protein was expressed not only in cartilage and tendon but in trachea, bone, skeletal muscle, eye, heart, and placenta as well, and no expression was found in other tissues. Immunohistology revealed that cartilage oligomeric matrix was deposited as early as 10 days post coitus in predifferentiated mouse embryo mesenchyme. It was detected in all cartilaginous tissues and in the skeletal muscles of the embryo at day 13. As development progressed, accumulation of cartilage oligomeric matrix protein was marked in the growth plate. At 19 days post coitus, it was prominently deposited in the hypertrophic zone of the growth plate, perichondrium, and periosteum and in the superficial layer of the articular cartilage surface but was absent in the more central areas of the epiphyseal cartilage. The restricted tissue distribution and expression of cartilage oligomeric matrix protein in developing as well as adult mouse tissues suggest the regulation of this protein at the transcriptional level. The findings reported herein are the first detailed characterization of the distribution of cartilage oligomeric matrix protein during early skeletal development of the mouse.

Animals↗

Expression of cartilage oligomeric matrix protein (COMP) by embryonic and adult osteoblasts.

Cartilage oligomeric matrix protein has been implicated as an important component of endochondral ossification because of its direct effects on chondrocytes. The importance of this protein for skeletal development and growth has been recently illustrated by the identification of mutations in cartilage oligomeric protein genes in two types of inherited chondrodysplasias and osteoarthritic phenotypes: multiple epiphyseal dysplasia and pseudoachondroplasia. In the present study, we report the presence of cartilage oligomeric protein in embryonic and adult osteoblasts. A foot from a 21-week-old human fetus, subchondral bone obtained from knee replacement surgery in an adult patient, and a limb from a 19-day-postcoital mouse embryo were analyzed with immunostaining and in situ hybridization. In the human fetal foot, cartilage oligomeric protein was localized to osteoblasts of the bone collar and at the newly formed bone at the growth plate and bone diaphyses. Immunostaining was performed on the adult subchondral bone and showed positive intracellular staining for cartilage oligomeric protein of the osteoblasts lining the trabecular bone. There was no staining of the osteocytes. Immunostaining of the mouse limb showed the most intense staining for cartilage oligomeric protein in the hypertrophic chondrocytes and in the surrounding osteoblast cells of the developing bone. Cartilage oligomeric protein mRNA and protein were detected in an osteoblast cell line (MG-63), and cartilage oligomeric protein mRNA was detected from human cancellous bone RNA. These results suggest that the altered structure of cartilage oligomeric protein by the mutations seen in pseudoachondroplasia and multiple epiphyseal dysplasia may have direct effects on osteoblasts, contributing to the pathogenesis of these genetic disorders.

Animals↗

Hip arthroplasty with a collared straight cobalt-chrome femoral stem using second-generation cementing technique: a 10-year-average follow-up study.

Clinical and radiographic results of 116 patients who had undergone 132 hip arthroplasties at our institution from 1983 to 1988 with a collared cemented straight cobalt-chrome femoral stem using second-generation cementing technique were reviewed. Twenty hips in 20 patients who were part of the original cohort were lost to follow-up. Mean age at the time of surgery was 68.2 years. Mean radiographic follow-up was 9.6 years with a minimum follow-up of 5 years. Ten-year survivorship of the component was 96.5% with revision considered as an endpoint and 94.2% with either revision or radiographic loosening considered the endpoint. Three implants (2.3%) were revised for aseptic loosening at a mean of 8.1 years after implantation. One implant (0.8%) was revised for septic loosening at 10.5 years after surgery. Of the implants not revised, 1 showed evidence of circumferential bone-cement radiolucencies, and 1 had radiolucencies at the implant-cement interface. Five of the surviving femoral components (5.0%) showed focal areas of cystic osteolysis, and proximal femoral bone resorption under the collar was seen in 32 patients (31.7%). There were no cases of cement fracture or stem subsidence. The biomechanical and material properties of this stem combined with second-generation cementing technique look promising for long-term survivorship.

Aged↗

The predictive value of indium-111 leukocyte scans in the diagnosis of infected total hip, knee, or resection arthroplasties.

To evaluate the usefulness of the indium-111 scan in detecting actually or potentially infected total hip, knee, and resection arthroplasties, 153 scans were performed on 143 patients who underwent reoperation for a loose or painful total joint arthroplasty or a resection arthroplasty between 1990 and 1996. Scans were interpreted as infected, not infected, or equivocal by an experienced nuclear medicine radiologist. Patients were considered to be infected if they met any 2 of the following criteria: i) positive intraoperative cultures, ii) final permanent histologic section indicating acute inflammation, and iii) intraoperative findings of gross purulence within the joint. Twenty-six patients (17%) met the infection criteria at the time of reoperation. Indium scans were found to have a 77% sensitivity, 86% specificity, 54% and 95% positive and negative predictive values, and 84% accuracy for the prediction of infection. Of 6 equivocal scans, none were infected. The results of this study suggest limited indications for the use of the indium-111 scan in the evaluation of painful hip, knee, or resection arthroplasties. A negative indium scan may be helpful in suggesting the absence of infection in cases in which the diagnosis is not otherwise evident.

Adult↗

The accuracy of computed tomography for determining femoral and tibial total knee arthroplasty component rotation.

Patellofemoral complications, instability, and tibial polyethylene wear after total knee arthroplasty (TKA) resulting from malrotation of the tibial or femoral components (or both) may be difficult to diagnose based on physical examination and standard knee radiographs. The preoperative assessment of implant rotational alignment is critical in planning treatment because the femoral or tibial component (or both) may need to be revised if malpositioned. The purpose of this study was to ascertain the accuracy of computed tomography (CT) scan for determining rotational alignment of femoral and tibial components in TKA. TKA components were inserted in human cadaver specimens at neutral and 5 degrees of external or internal rotation. For each position, the amount of rotation, determined from digital photographs, was compared with CT scan. The correlation coefficient between these two values averaged 0.87, which was significant at P < .05. The CT scan protocol described in this study can be applied clinically to patients with patellofemoral complaints to confirm or rule out the presence of component malrotation.

Arthroplasty, Replacement, Knee↗

Anticoagulant treatment of thromboembolism with intravenous heparin therapy in the early postoperative period following total joint arthroplasty.

BACKGROUND: Treatment of thromboembolism with intravenous heparin therapy in the early postoperative period after total joint arthroplasty has been associated with a high rate of complications. The purpose of the present study was to compare the rate of bleeding complications in a group of patients who required intravenous heparin therapy for the treatment of thromboembolism after total hip or knee arthroplasty with the rate in a control group of patients who received only prophylactic anticoagulation. METHODS: The postoperative courses of forty-four consecutive patients who were managed with intravenous administration of heparin and oral administration of warfarin for the treatment of a thromboembolic event following unilateral total hip or knee arthroplasty were compared with those of a control group of 376 consecutive patients who had these same procedures but did not have a thromboembolic complication. The patients in the control group were managed with prophylactic anticoagulation with use of enoxaparin. Sixty-eight percent (thirty) of the forty-four patients in the heparin group received the initial dose of heparin on or before the fourth postoperative day, and 82 percent (thirty-six) received an initial bolus of 5000 units of heparin at the initiation of therapy. RESULTS: The rate of bleeding complications was 9 percent (four of forty-four) in the heparin group, compared with 6 percent (twenty-three of 376) in the control group (p = 0.44). The mean transfusion requirement in the heparin group (1.8 units of packed red blood cells) was significantly greater than that in the control group (0.8 unit) (p < 0.0001). Three of the four patients who had a bleeding complication while receiving heparin and warfarin had coagulation parameters that were substantially higher than recommended levels. The mean duration of hospitalization in the heparin group (fifteen days) was significantly longer than that in the control group (seven days) (p < 0.0001). CONCLUSIONS: The results of the present study suggest that the use of intravenous heparin therapy for the treatment of thromboembolism in the early postoperative period after total joint arthroplasty is associated with a rate of bleeding complications that is similar to that associated with the use of prophylactic anticoagulation with use of enoxaparin alone. One should expect an increased transfusion requirement and a longer duration of hospitalization for patients who require intravenous heparin therapy for the treatment of a thromboembolic event.

Adult↗

Viscosupplementation for osteoarthritis.

Viscosupplementation therapy can restore the elastic and viscous properties of synovial fluid and thus recreate the intra-articular joint homeostasis that is disrupted in the degenerative joint. Hyaluronan (hyaluronic acid) products have been developed and used for viscosupplementation therapy in osteoarthritis. Viscosupplementation treatments using these products are well tolerated. Because viscosupplementation therapy is based on the concept of replenishing a normal physiological component of synovial fluid and cartilaginous tissue, exogenous administration of hyaluronic acid has the potential to have few side effects or local or systemic reactions. Viscosupplementation represents an alternative treatment for patients with osteoarthritis in which oral medications and/or surgery are not options or are ineffective.

Chemistry, Pharmaceutical↗