Biomedical subjects

Paul E Di Cesare

Publications and source records attributed to Paul E Di Cesare.

At least 19 recordsLinked to original sources

PubMed2007

Factors associated with prolonged wound drainage after primary total hip and knee arthroplasty.

BACKGROUND: Prolonged wound drainage following total hip or total knee arthroplasty has been associated with an increased risk of postoperative morbidity. The purpose of this study was to determine the pharmacologic, surgical, and patient-specific factors that are associated with prolonged wound drainage and the relationship of this complication to the length of hospital stay and the rate of wound infections. METHODS: We conducted a retrospective observational study of 1211 primary total hip arthroplasties and 1226 primary total knee arthroplasties. Prospectively collected data included body mass index, intraoperative blood loss, surgical time, type of prophylaxis against deep venous thrombosis, and length of hospital stay. The association of these factors with the duration of postoperative wound drainage was analyzed. An acute infection developed after fifteen primary total hip arthroplasties and ten primary total knee arthroplasties. The patients with an acute postoperative infection were compared with their uninfected counterparts, and an odds ratio was determined to estimate the risk of prolonged wound drainage resulting in a wound infection. RESULTS: Morbid obesity was strongly associated with prolonged wound drainage in the total hip arthroplasty group (p = 0.001) but not in the total knee arthroplasty group (p = 0.590). An increased volume of drain output was an independent risk factor for prolonged wound drainage in both groups. Patients who received low-molecular-weight heparin for prophylaxis against deep venous thrombosis had a longer time until the postoperative wound was dry than did those treated with aspirin and mechanical foot compression or those who received Coumadin (warfarin); this difference was significant on the fifth postoperative day (p = 0.003) but not by the eighth postoperative day. Prolonged wound drainage resulted in a significantly longer hospital stay in both groups (p < 0.001). Each day of prolonged wound drainage increased the risk of wound infection by 42% following a total hip arthroplasty and by 29% following a total knee arthroplasty. CONCLUSIONS: Morbid obesity, the use of low-molecular-weight heparin, and a higher drain output were associated with a prolonged time until the postoperative wound was dry following a primary total hip arthroplasty, whereas a higher drain output was the only risk factor associated with prolonged drainage following a primary total knee arthroplasty. Prolonged drainage was associated with a higher rate of infection following a primary total hip arthroplasty, whereas obesity was the only identified independent risk factor for postoperative infection following a primary total knee arthroplasty.

Aged↗

PubMed2006

Midterm results of primary total knee arthroplasty using a dished polyethylene insert with a recessed or resected posterior cruciate ligament.

Use of a dished polyethylene insert in 114 total knee arthroplasties, all with the posterior cruciate ligament resected or recessed, was retrospectively studied. Patients were evaluated at a mean follow-up of 8.3 years. Mean range of motion increased from 92 degrees to 111 degrees . Mean Knee Society pain and function scores increased from 35.2 and 39.7 to 91.3 and 74.7, respectively. WOMAC scores improved significantly in each category evaluated, including pain, stiffness, and physical function. Kaplan-Meier survivorship was 95% at 10 years (95% confidence interval, 82%-99%). The use of a dished polyethylene insert in primary total knee arthroplasty provides good to excellent midterm results regardless of whether the posterior cruciate ligament is recessed or sacrificed.

Adult↗

PubMed2006

ADAMTS-12 associates with and degrades cartilage oligomeric matrix protein.

Loss of articular cartilage because of extracellular matrix breakdown is the hallmark of arthritis. Degradative fragments of cartilage oligomeric matrix protein (COMP), a prominent noncollagenous matrix component in articular cartilage, have been observed in the cartilage, synovial fluid, and serum of arthritis patients. The molecular mechanism of COMP degradation and the enzyme(s) responsible for it, however, remain largely unknown. ADAMTS-12 (a disintegrin and metalloprotease with thrombospondin motifs) was shown to associate with COMP both in vitro and in vivo. ADAMTS-12 selectively binds to only the epidermal growth factor-like repeat domain of COMP of the four functional domains tested. The four C-terminal TSP-1-like repeats of ADAMTS-12 are shown to be necessary and sufficient for its interaction with COMP. Recombinant ADAMTS-12 is capable of digesting COMP in vitro. The COMP-degrading activity of ADAMTS-12 requires the presence of Zn2+ and appropriate pH (7.5-9.5), and the level of ADAMTS-12 in the cartilage and synovium of patients with both osteoarthritis and rheumatoid arthritis is significantly higher than in normal cartilage and synovium. Together, these findings indicate that ADAMTS-12 is a new COMP-interacting and -degrading enzyme and thus may play an important role in the COMP degradation in the initiation and progression of arthritis.

ADAM Proteins↗

PubMed2006

ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein.

Degradative fragments of cartilage oligomeric matrix protein (COMP) have been observed in arthritic patients. The physiological enzyme(s) that degrade COMP, however, remain unknown. We performed a yeast two-hybrid screen (Y2H) to search for proteins that associate with COMP to identify an interaction partner that might degrade it. One screen using the epidermal growth factor (EGF) domain of COMP as bait led to the discovery of ADAMTS-7. Rat ADAMTS-7 is composed of 1595 amino acids, and this protein exhibits higher expression in the musculoskeletal tissues. COMP binds directly to ADAMTS-7 in vitro and in native articular cartilage. ADAMTS-7 selectively interacts with the EGF repeat domain but not with the other three functional domains of COMP, whereas the four C-terminal TSP motifs of ADAMTS-7 are required and sufficient for association with COMP. The recombinant catalytic domain and intact ADAMTS-7 are capable of digesting COMP in vitro. The enzymatic activity of ADAMTS-7 requires the presence of Zn2+ and appropriate pH (7.5-9.5), and the concentration of ADAMTS-7 in cartilage and synovium of patients with rheumatoid arthritis is significantly increased as compared to normal cartilage and synovium. ADAMTS-7 is the first metalloproteinase found to bind directly to and degrade COMP.

ADAM Proteins↗

PubMed2006

Regional gene therapy for full-thickness articular cartilage lesions using naked DNA with a collagen matrix.

A novel gene therapy approach for treating damaged cartilage is proposed that involves placing endotoxin-free cDNA containing the gene for bone morphogenetic protein-2 (BMP-2) in type I collagen sponges and then transferring the naked plasmid DNA construct to the injury site. A full-thickness cartilaginous defect in rabbits implanted with plasmid containing a marker gene (beta-galactosidase) showed expressed protein as detected by immunostaining. At 1 week postimplantation, mesenchymal cells subjacent to the defect had incorporated the implanted naked plasmid DNA and, once transfected, served as local bioreactors, transiently producing the gene product. Plasmids containing the gene for BMP-2 implanted in collagen sponges in cartilage lesions stimulated hyalinelike articular cartilage repair at 12 weeks postimplantation, nearly equivalent in quality to that induced by collagen sponges with recombinant BMP-2 protein. Our approach circumvents the risks of inflammation and immunogenic response associated with the use of viral vectors. Naked plasmid DNA as a vehicle for transferring therapeutic genes has been shown to be effective in a therapeutic model within rabbit articular cartilage and appears to be safe and cost effective.

Animals↗

PubMed2006

A proposed classification of supracondylar femur fractures above total knee arthroplasties.

A new classification system is proposed for supracondylar femur fractures above total knee arthroplasties based on fracture location relative to the femoral component. Radiographs of 28 cases were evaluated and classified according to the proposed system by 12 physicians: 3 trauma specialists, 3 adult reconstruction specialists, 3 musculoskeletal radiologists, and 3 orthopaedic residents. The same 12 physicians reevaluated the same 28 cases 3 months later. The mean reliability coefficient for all observers was 0.74 (substantial agreement). The coefficient for reproducibility after 3 months was 0.85 (almost perfect). The power of the study was 80%. The proposed classification system is easy to use and has good interobserver reliability among orthopaedic residents, orthopaedic attendings--trauma and reconstruction--and radiologists. Intraobserver reliability was also excellent at 3 months.

Arthroplasty, Replacement, Knee↗

PubMed2006

Antibiotic susceptibility of bacteria infecting total joint arthroplasty sites.

BACKGROUND: Currently, there is no consensus regarding the principles of empiric antibiotic treatment of suspected periprosthetic infection following total knee and hip arthroplasties. This study was undertaken to attempt to establish such principles. METHODS: We performed a retrospective analysis of 146 patients who had had a total of 194 positive cultures of specimens obtained at the time of a reoperation following a total knee or total hip arthroplasty at one of two institutions. Patient demographic data, comorbid conditions, bacterial species, the antibiotic sensitivity profile, and the postoperative day on which the culture tested positive were recorded. RESULTS: Specimens from 110 hips and eighty-four knees were positive on culture. Seventy percent of the infections were classified as chronic; 17%, as acute postoperative; and 13%, as acute hematogenous. The mean time between the operation and the positive culture results was three days. Gram-positive organisms caused the majority of the infections. In the series as a whole, 88% of the bacteria were sensitive to gentamicin; 96%, to vancomycin; and 61%, to cefazolin. The most antibiotic-resistant bacterial strains were from patients for whom prior antibiotic treatment had failed. Acute postoperative infections had a greater resistance profile than did chronic or hematogenous infections. Bacteria isolated from patients with a hematogenous infection had a high sensitivity to both cefazolin and gentamicin. CONCLUSIONS: Empiric antibiotic treatment for suspected periprosthetic infection should be guided by the class of the infection and the findings of Gram staining. We believe that, until the final culture results are available, acute hematogenous infections should initially be treated by a combination of cefazolin and gentamicin therapy. All chronic and acute postoperative infections with Gram-positive bacteria and all cases in which a Gram stain fails to identify bacteria should be managed with vancomycin. Infections with Gram-negative bacteria should be managed with a third or fourth-generation cephalosporin. Infections with mixed Gram-positive and Gram-negative bacteria should be managed with a combination of vancomycin and a third or fourth-generation cephalosporin. Furthermore, we believe that if culture results and other confirmatory tests are not positive by the fourth postoperative day, termination of empiric antibiotic therapy should be considered.

Adult↗

PubMed2006

Multidisciplinary management of orthopedic patients with sickle cell disease.

With pharmacological treatment, the lifespan of the patient with sickle cell disease can be extended to the sixth decade. Currently the only curative therapy for sickle cell disease is hemopoietic cell transplantation, which is still undergoing technical refinement. Most patients can be expected to undergo at least one orthopedic surgical procedure in their lifetime. Multidisciplinary management of orthopedic patients with sickle cell disease will decrease the overall complication rates and improve clinical outcomes.

Anemia, Sickle Cell↗

PubMed2006

Orthopedic surgical management of hip and knee involvement in patients with juvenile rheumatoid arthritis.

Juvenile rheumatoid arthritis is the most common arthritic disease of childhood and a leading cause of childhood disability, affecting an estimated 300,000 US children and adolescents aged < or =16 years. Approximately 10% to 30% of patients experience functional deficits resulting from both the articular and systemic manifestations of their disease, including leg length inequality and deformity, that are often more crippling than joint destruction. Surgical intervention to treat bone and soft-tissue deformity, leg length inequality, and joint destruction is indicated when medical therapy has failed. Synovectomy, soft-tissue release, osteotomy, and epiphysiodesis are used to treat deformity and early joint destruction. Arthroplasty remains the primary therapy for joint destruction, although it is fraught with complications specific to this young patient population.

Arthritis, Juvenile↗

PubMed2006

Nonsurgical complications after total hip and knee arthroplasty.

Postoperative medical complications after total hip arthroplasty (THA) and total knee arthroplasty (TKA) may occur in patients of any age. However, percentage of adverse events increases with increasing patient age and can cause significant morbidity and even mortality. It is important that the orthopedist identify risk factors and symptoms and be knowledgeable in the treatment of nonsurgical postoperative complications. Nonsurgical complications after THA and TKA include pulmonary embolism, fat embolism syndrome, pneumonia, myocardial infarction, postoperative delirium, cerebrovascular accident, urinary retention, urinary tract infections, and deep vein thrombosis.

Arthroplasty, Replacement, Hip↗

PubMed2005

Stress risers between two ipsilateral intramedullary stems: a finite-element and biomechanical analysis.

Periprosthetic fracture after total joint replacement predominantly occurs at the stem tip. In this study, the effects of gap size, stem stability and cortical thickness between two press-fit, ipsilateral intramedullary stems on the tensile stresses created in the femur were investigated using finite-element models. The findings were confirmed with strain-gauge tests using a composite Sawbone femur. Gap size did not affect the level of stress on the femur. Cortical thickness had an important effect on stress distribution: peak stresses increased as bone cortical thickness decreased. Irrespective of gap size, the tips of loose stems acted as stress risers particularly with thinner cortices; the tips of well-fixed stems, however, did not.

Biomechanical Phenomena↗

PubMed2005

Osteotomy about the knee: applications, techniques, and results.

Varus or valgus malalignment of the knee may be either a cause or a consequence of unicompartmental knee arthritis in young, active adults. Proximal tibial osteotomy for the varus knee and distal femoral osteotomy for the valgus knee have been used for decades to manage this condition; however, their use has decreased significantly in recent years as the popularity of unicompartmental and total knee arthroplasty has grown. With the advent of biologic resurfacing techniques for focal full-thickness articular cartilage injury, combined or staged high tibial osteotomy is becoming increasingly popular. In addition, in the face of cruciate ligamentous instability with or without posterolateral corner instability coupled with varus malalignment, high tibial osteotomy with and without ligament reconstruction provides a solution to complex orthopedic problems. Recent long-term follow-up studies have concluded osteotomy allows for improved function and pain relief in properly selected young patients.

Arthroplasty, Replacement, Knee↗

PubMed2005

Serum interleukin-6 as a marker of periprosthetic infection following total hip and knee arthroplasty.

BACKGROUND: The erythrocyte sedimentation rate, the C-reactive protein serum level, and the white blood-cell count are routinely used to diagnose periprosthetic infection. In the present study, the diagnostic accuracy of the interleukin-6 serum level was compared with the accuracy of these standard tests for the evaluation of a group of patients who had had a total hip or total knee arthroplasty and were undergoing a reoperation for the treatment of an infection or another implant-related problem. METHODS: A prospective, case-control study of fifty-eight patients who had had a total hip or knee replacement and were undergoing a reoperation because of an infection (seventeen patients) or another implant-related problem (forty-one patients) was conducted. The serum levels of interleukin-6 and C-reactive protein, the erythrocyte sedimentation rate, and the white blood-cell count were measured. The definitive diagnosis of an infection was determined on the basis of positive histopathological evidence of infection and growth of bacteria on culture of intraoperative specimens. Two-sample Wilcoxon rank-sum (Mann-Whitney) tests were used to determine the presence of a significant difference between patients with and without infection with regard to each laboratory value studied. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of each text were also calculated. RESULTS: The serum interleukin-6 level, erythrocyte sedimentation rate, and C-reactive protein level were significantly higher in patients who had an infection than in those who did not, both when all patients were considered together and when the total hip arthroplasty and total knee arthroplasty groups were considered separately. With the numbers available, there was no significant difference with regard to the white blood-cell count between patients with and without infection. With a normal serum interleukin-6 level defined as <10 pg/mL, the serum interleukin-6 test had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 1.0, 0.95, 0.89, 1.0, and 97%, respectively. CONCLUSIONS: An elevated serum interleukin-6 level correlated positively with the presence of periprosthetic infection in patients undergoing a reoperation at the site of a total hip or knee arthroplasty. The serum interleukin-6 level is valuable for the diagnosis of periprosthetic infection in patients who have had a total hip or total knee arthroplasty.

Adult↗

PubMed2005

Disease-modifying therapies for osteoarthritis : current status.

Osteoarthritis, the most common form of arthritis, is a debilitating progressive disease principally affecting the elderly. Osteoarthritis therapy has evolved in the past few decades from symptomatic treatment to possible disease-modifying solutions. In this paper, the pathophysiology of osteoarthritis is first reviewed, including an examination of the mechanisms underlying osteoarthritis and discussions of the roles of cartilage, synovial fluid and subchondral bone. The remainder of the paper discusses therapeutic approaches in current use and those in development, with special attention given to pharmacological treatments. Current approaches to treating osteoarthritis--i.e. medications; nonpharmacological modalities, such as physical therapy, exercise, weight management and orthotics; and (as a last resort) surgery--focus on reducing pain and improving (or at least maintaining) mobility. Drugs currently used to treat osteoarthritis fall into several categories: analgesics, NSAIDs, cyclo-oxygenase-2 (COX-2) inhibitors, corticosteroids, viscosupplementation, and symptomatic slow-acting drugs ('nutraceuticals'). The analgesics (paracetamol [acetaminophen] and opiates) have demonstrated less symptomatic efficacy than NSAIDs, while the latter have displayed mixed results in terms of joint space narrowing. COX-2 inhibitors have been demonstrated to be equal to or superior to NSAIDs in effectiveness. However, once considered a safer alternative, COX-2 inhibitors have become the subject of intense scrutiny since recent clinical evidence has cast suspicion on their cardiovascular safety profile. Injectable therapies, such as corticosteroids and viscosupplementation have elicited favorable short-term response but no long-term structural modification. On the other hand, the slow-acting drugs, especially chondroitin and glucosamine sulfate, have shown promising results. Also reviewed are other established and experimental therapies that seek to modify and/or even reverse the course of osteoarthritis. These include such medications as colchicine, bisphosphonates and hormones; dietary therapeutics, such as ginger extract and green tea; and such truly experimental treatments as matrix metalloproteinase inhibitors, cytokines, nitric oxide, growth factors and gene therapy. Osteoarthritis continues to be a difficult disorder to treat, as there is no cure as such and current treatments focus mainly on relieving pain and maintaining joint function. The search nevertheless continues for management regimens that can slow, alter or reverse the degenerative processes of osteoarthritis.

Aged↗

PubMed2005

Management of extensor mechanism disruptions occurring after total knee arthroplasty.

Extensor mechanism disruption from quadriceps tendon rupture, patellar fracture, or patellar tendon rupture is an uncommon complication of total knee arthroplasty. Extensor mechanism disruption can occur either intraoperatively or postoperatively. Common intraoperative causes include avulsion or tendon injury arising from excessive tension during surgical exposure, improper patellar resection, and devascularization due to injudicious lateral retinacular release or multiple prior surgeries. The usual postoperative causes are tissue necrosis arising from infection, component malalignment, and trauma. A wide range of treatment options is available for managing these difficult problems, and recent advances in alternative techniques for reconstruction have yielded promising results.

Arthroplasty, Replacement, Knee↗

PubMed2004

The interferon-inducible p204 protein acts as a transcriptional coactivator of Cbfa1 and enhances osteoblast differentiation.

The differentiation of uncommitted mesenchymal cells into osteoblasts is a fundamental molecular event governing both embryonic development and bone repair. The bone morphogenetic proteins (BMPs) are important regulators of this process; they function by binding to cell surface receptors and signaling by means of Smad proteins. Core binding factor alpha-1 (Cbfa1), a member of the runt family of transcription factors, is an essential transcriptional regulator of osteoblast differentiation and bone formation, and this process is positively or negatively regulated by a variety of coactivators and corepressors. We report that p204, an interferon-inducible protein that was previously shown to inhibit cell proliferation and promote the differentiation of myoblasts to myotubes, is a novel regulator in the course of osteogenesis. p204 is expressed in embryonic osteoblasts and hypertrophic chondrocytes in the growth plate as well as in the calvaria osteoblasts of neonatal mice. Its level is increased in the course of the BMP-2-triggered osteoblast differentiation of pluripotent C2C12 cells. This increase is probably due to the activation of the gene encoding 204 (Ifi204) by Smad transcription factor, including Smad1, -4, and -5. Overexpression of p204 enhances the BMP-2-induced osteoblast differentiation in vitro, as revealed by elevated alkaline phosphatase activity and osteocalcin production. p204 acts as a cofactor of Cbfa1: 1) high levels of p204 augment, whereas the lowering of p204 level decreases, the Cbfa1-dependent transcription, and 2) p204 associates with Cbfa1 both in vitro and in vivo. Two nonoverlapping segments in p204 bind to Cbfa1, and the N-terminal 88-amino acid segment of Cbfa1 is required for binding to p204. p204, which is the first interferon-inducible protein found to associate with Cbfa1, functions as a novel regulator of osteoblast differentiation.

Alkaline Phosphatase↗

PubMed2004

Leukemia/lymphoma-related factor, a POZ domain-containing transcriptional repressor, interacts with histone deacetylase-1 and inhibits cartilage oligomeric matrix protein gene expression and chondrogenesis.

Mutations in the human cartilage oligomeric matrix protein (COMP) gene have been linked to the development of pseudoachondroplasia and multiple epiphyseal dysplasia. We previously cloned the promoter region of the COMP gene and delineated a minimal negative regulatory element (NRE) that is both necessary and sufficient to repress its promoter (Issack, P. S., Fang, C. H., Leslie, M. P., and Di Cesare, P. E. (2000) J. Orthop. Res. 18, 345-350; Issack, P. S., Liu, C. J., Prazak, L., and Di Cesare, P. E. (2004) J. Orthop. Res. 22, 751-758). In this study, a yeast one-hybrid screen for proteins that associate with the NRE led to the identification of the leukemia/lymphoma-related factor (LRF), a transcriptional repressor that contains a POZ (poxvirus zinc finger) domain, as an NRE-binding protein. LRF bound directly to the NRE both in vitro and in living cells. Nine nucleotides (GAGGGTCCC) in the 30-bp NRE are essential for binding to LRF. LRF showed dose-dependent inhibition of COMP-specific reporter gene activity, and exogenous overexpression of LRF repressed COMP gene expression in both rat chondrosarcoma cells and bone morphogenetic protein-2-treated C3H10T1/2 progenitor cells. In addition, LRF also inhibited bone morphogenetic protein-2-induced chondrogenesis in high density micromass cultures of C3H10T1/2 cells, as evidenced by lack of expression of other chondrocytic markers, such as aggrecan and collagen types II, IX, X, and XI, and by Alcian blue staining. LRF associated with histone deacetylase-1 (HDAC1), and experiments utilizing the HDAC inhibitor trichostatin A revealed that LRF-mediated repression requires deacetylase activity. LRF is the first transcription factor found to bind directly to the COMP gene promoter, to recruit HDAC1, and to regulate both COMP gene expression and chondrogenic differentiation.

Alcian Blue↗

PubMed2004

Risks associated with blood transfusion after total knee arthroplasty.

A retrospective study of 1,402 patients who underwent primary total knee arthroplasty (TKA) (1,194 unilateral, 208 bilateral) was performed. The strongest predictors for allogenic transfusion after surgery were advancing age (P<.001), low preoperative hemoglobin (P<.001), and the use of low-molecular-weight heparin postoperatively (P<.01). Pre-donation of 1 unit of autologous blood before TKA decreased the allogenic transfusion rate from a baseline of 38% to 11%, whereas pre-donating 2 units lowered the rate of breakthrough transfusion of allogenic blood to 7%. A patient with a preoperative hemoglobin >150 g/L or who is younger than age 65 with a preoperative hemoglobin >130 g/L may not benefit from pre-donation, and a high rate of wastage may result.

Age Factors↗