Biomedical subjects

Joel A Block

Publications and source records attributed to Joel A Block.

27 records · Page 2Linked to original sources

PubMed2003

The risk of contralateral total knee arthroplasty after knee replacement for osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is the most common indication for total knee arthroplasty (TKA), but the rate of contralateral disease progression after unilateral TKA as well as risk factors that may predict progression have not been determined. We assessed the overall rate of contralateral knee replacement after initial TKA for OA as a marker of progression to advanced symptomatic OA. METHODS: A total of 117 consecutive patients undergoing unilateral TKA for OA between 1983 and 1988 were evaluated and followed longitudinally for up to 14 years. Evaluation of potential risk factors for progression to contralateral TKA included age, sex, side of surgery, body mass index (BMI), and Kellgren-Lawrence (K-L) grade. RESULTS: The contralateral knee progressed to TKA in 31 patients, yielding an overall 10-year risk of contralateral TKA of 37.2%. The baseline K-L grade of the contralateral knee was strongly correlated with future risk of TKA (p < 0.001). Mean survival times were similar for those with grade II (131.7 mo) and grade III (127.6 mo); patients with grade IV, however, had a mean survival of 80.5 months, with an overall 10-year risk of TKA of 62.7%. Age, sex, side of initial TKA, and BMI were not risk factors for progression to contralateral TKA. CONCLUSION: In this cohort, the K-L grading scale was a highly significant predictor for progression of contralateral OA to TKA. These data may provide important information to patients undergoing TKA, and shed light on the natural history of contralateral OA after TKA.

Adult↗

PubMed2002

Cancer/testis antigen CSAGE is concurrently expressed with MAGE in chondrosarcoma.

Differential display-polymerase chain reaction was used to compare gene expression between human chondrosarcoma cell lines and normal cartilage. A new gene, CSAGE, has been cloned and belongs to a gene family that includes the taxol resistance associated gene (TRAG)-3. CSAGE, like TRAG-3, does not confer resistance to taxol when transfected in vitro. Both genes have alternatively spliced variants. CSAGE and TRAG-3 are expressed in chondrosarcoma, melanoma, and cartilage and testis, but not in other normal tissues. TRAG-3 has been reported to be a cancer/testis antigen. Our results suggest that CSAGE belongs to the growing list of cancer/testis antigens as well. In all of the CSAGE positive samples, the melanoma antigen gene family was also expressed. This is the first report on the expression of cancer/testis antigens in chondrosarcoma.

Alternative Splicing↗

PubMed2002

Drug-induced systemic lupus erythematosus associated with etanercept therapy.

Specific antagonists of tumour necrosis factor (TNF)-alpha have rapidly gained popularity for the treatment of rheumatoid arthritis. The monoclonal antibody against TNF-alpha, infliximab, has been associated with induction of systemic lupus erythematosus (SLE); however, there have been no published reports of drug-induced SLE associated with the soluble TNF-alpha receptor etanercept. We describe four female patients who developed signs and symptoms of SLE during treatment with etanercept; in two SLE was unambiguous. On diagnosis of SLE, etanercept was discontinued and the SLE-related symptoms promptly resolved. Etanercept should be considered in the list of agents associated with drug-induced SLE.

Adult↗

PubMed2002

Efficacy of tacrolimus in rheumatoid arthritis patients who have been treated unsuccessfully with methotrexate: a six-month, double-blind, randomized, dose-ranging study.

OBJECTIVE: To assess the efficacy, safety, and optimal dose of tacrolimus monotherapy in patients with rheumatoid arthritis (RA). METHODS: This phase II, randomized, double-blind, placebo-controlled monotherapy study was set in 12 community sites and 9 university-based sites. Two hundred sixty-eight patients with RA who were resistant to or intolerant of methotrexate (mean dose 15.2 mg/week) and had active disease for at least 6 months (mean tender joint count 28.2, mean erythrocyte sedimentation rate 46.5 mm/hour) were randomized to receive treatment after discontinuation of methotrexate. Those who received at least 1 dose of tacrolimus were analyzed; 141 completed the study. Stable dosages of nonsteroidal antiinflammatory drugs and low-dose prednisone were allowed during treatment. All patients were given 1, 3, or 5 mg of tacrolimus or placebo once daily for 24 weeks. The American College of Rheumatology definition of 20% improvement (ACR20) and the tender and swollen joint counts at the end of treatment were the primary outcomes. RESULTS: ACR20 response rates demonstrated a clear dose response. The ACR20 response was observed in 15.5% of patients receiving placebo (95% confidence interval [95% CI] 7.1-23.9%), 29% of the 1 mg tacrolimus group (95% CI 18.3-39.7%) (P < 0.058); 34.4% of the 3 mg group (95% CI 22.7-46.0%) (P < 0.013), and 50% of the 5 mg group (95% CI 37.8-62.3%) (P < or = 0.001). The tender joint count improved statistically significantly in all tacrolimus groups. The swollen joint count, physical function, and patient-assessed pain improved statistically significantly in the 3 mg and 5 mg groups. The incidence of creatinine elevation > or =40% above baseline levels increased in a dose-dependent manner. Dropout rates were high (41-59%) and were more common for inefficacy in the placebo patients (71.4%), whereas they were more common for toxicity in the high-dose tacrolimus groups (31-33%). Discontinuation for creatinine elevation occurred in the 3 mg (3.1%) and 5 mg (10.9%) tacrolimus groups. CONCLUSION: Tacrolimus improved disease activity in methotrexate-resistant or -intolerant patients with RA. A dose response was observed when efficacy and toxicity were assessed at different doses. The optimal dose of tacrolimus appears to be >1 mg but < or=3 mg daily.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Nonrandom evolution of end-stage osteoarthritis of the lower limbs.

OBJECTIVE: Patients with unilateral hip or knee replacements for end-stage osteoarthritis (OA) are at high risk for future progression of OA in other joints of the lower extremities, often requiring additional joint replacements. Although the risks of future surgery in the contralateral cognate joints (i.e., contralateral hip replacement after an initial hip replacement) have been evaluated, the evolution of end-stage hip OA to OA involving the knee joints, and vice versa (i.e., noncognate progression) has not been investigated. Because characterization of OA progression in noncognate joints may shed light on the pathogenesis of multijoint OA, we investigated the pattern of evolution of end-stage lower extremity OA in a large, clinical cohort. METHODS: Total joint replacement (TJR) was selected as a marker of end-stage OA, and a database comprising all lower extremity TJRs performed at a large referral center between 1981 and 2001 was accessed. Of the 5,894 patients identified, 486 patients with idiopathic OA who underwent hip replacement and 414 who underwent initial knee replacement were analyzed to determine the relative likelihood of subsequent TJRs. Patients with the systemic inflammatory arthropathy, rheumatoid arthritis (RA), were evaluated as a control population because RA progression is not considered to be a primarily mechanically mediated process. RESULTS: The contralateral cognate joint was the most common second joint to undergo replacement in both the OA and the RA groups. However, in OA patients for whom the second TJR was in a noncognate joint, that joint was >2-fold more likely to be on the contralateral limb than on the ipsilateral limb (hip to knee P < 0.001; knee to hip P = 0.013). In contrast, among the RA cohort, the evolution was random and no laterality for noncognate TJR was observed at either the hip or the knee (P = 0.782). CONCLUSION: This characterization of end-stage lower extremity OA demonstrates that the disease evolves nonrandomly; after 1 joint is replaced, the contralateral limb is significantly more likely to show progression of OA than is the ipsilateral limb. Thus, OA in 1 weight-bearing joint appears to influence the evolution of OA in other joints. The absence of such laterality in RA suggests that OA progression may be mediated by extrinsic factors such as altered joint loading.

Arthroplasty, Replacement, Hip↗

PubMed2002

Tenascin-C expression and distribution in cultured human chondrocytes and chondrosarcoma cells.

Tenascin-C (TNC) is an oligomeric glycoprotein of the extracellular matrix with several distinct isoforms variably expressed during embryogenesis, tumorogenesis, angiogenesis and wound healing. In the normal human adult, TNC is found in large concentrations in articular cartilage, suggesting tissue-specific function. The purpose of this study was to determine the specific in vitro TNC splicing patterns of articular chondrocytes and a human chondrosarcoma cell line. Cells were cultured in a three-dimensional bead system and TNC splice variant expression and distribution were examined with the use of Western blotting techniques, semi-quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. At both the transcriptional and post-translational levels, the chondrocytes were found to express significantly higher levels of the smaller 220 kDa isoform (P < 0.01), which was predominantly incorporated into the matrix. The splicing pattern of the malignant cells was characterized by a higher proportion of the larger 320 kDa isoform which was extruded into the media. In vivo studies are necessary to verify the expression of the large TNC isoform in chondrosarcoma and the production and integration of the smaller isoform in normal chondroid matrix. In addition, elucidation of the biologic functions of the two major TNC isoforms may lead to the development of novel diagnostic and therapeutic approaches to chondrosarcoma.

Blotting, Western↗

PubMed2002

Malignant transformation in human chondrosarcoma cells supported by telomerase activation and tumor suppressor inactivation.

Human chondrosarcomas do not respond to current chemotherapies or radiation therapy, and their size and histological appearance do not reliably predict the risk of local recurrence and metastases, making selection of surgical treatment difficult. Identifying mechanisms responsible for the proliferation and invasive behavior of these tumors would be of immense clinical value. We hypothesized that telomerase expression is one of these mechanisms. We detected telomerase expression in 7 of 16 chondrosarcomas, but cells cultured from telomerase-negative chondrosarcomas acquired strong telomerase activity and lost tumor suppressor activity after their establishment in culture. These changes were associated with accelerated indefinite cell proliferation, morphological transition, and increased invasive activity, indicating that telomerase activation and loss of cell cycle control leads to the emergence of aggressive cells from chondrosarcoma cell populations. These observations may lead to better understanding of the factors responsible for malignant transformation, local recurrence, and metastases of cartilage neoplasms.

Adult↗

PubMedDate not supplied

The treatment of psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic, autoimmune, seronegative inflammatory arthritis characterized by varying degrees of axial and peripheral arthritis. Here, we review the literature on the pharmacological management of PsA and present a simple treatment algorithm based on the available information. Although PsA management must be individualized to the degree and type of joint pain and inflammation, in general, nonsteroidal antiinflammatory drugs (NSAIDs) still represent first-line treatment of mild PsA. Second-line therapy includes older agents such as gold salts, methotrexate, sulfasalazine, and cyclosporine. The tumor necrosis factor alpha (TNF-alpha) antagonists represent the most recent major advance in the clinical management of PsA.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMedDate not supplied

Daily needle aspiration versus surgical lavage for the treatment of bacterial septic arthritis in adults.

Septic arthritis is a substantial public health problem, accounting for 0.2-0.7% of hospital admissions. However, despite the availability of effective antibiotics, the appropriate approach to adjunctive therapy remains controversial. Although early drainage is essential to minimize the risks of permanent loss of articular function, it is unclear whether the optimal approach involves arthroscopic lavage or daily arthrocentesis; surgeons appear to prefer surgical lavage because their training routinely considers septic arthritis to be a closed-space infection comparable to an abscess, whereas rheumatologists appear to prefer daily arthrocentesis because of its ease and non-invasive nature. There is a paucity of prospective data comparing the two approaches, and the literature is largely retrospective. Herein, we review the available literature concerning drainage of bacterially infected joints, and conclude that in the absence of prospective randomized clinical trials, the best evidence suggests that there is no compelling reason to recommend surgical lavage for the initial management of uncomplicated septic arthritis.

Arthritis, Infectious↗