A clinical model including protein biomarkers predicts radiographic knee osteoarthritis: a prospective study using data from the Osteoarthritis Initiative.

OBJECTIVE: We aimed to provide a model to predict the prospective development of radiographic KOA (rKOA). METHOD: Baseline sera from 333 non-radiographic KOA subjects belonging to OA Initiative (OAI) who developed or not, rKOA during a follow-up period of 96 months were used in this study. The exploratory cohort included 200 subjects, whereas the replication cohort included 133. The levels of inter-alpha trypsin inhibitor heavy chain 1 (ITIH1), complement C3 (C3) and calcyclin (S100A6), identified in previous large proteomic analysis, were analyzed by using sandwich immunoassays on suspension bead arrays. The association of protein levels and clinical covariates with rKOA incidence was assessed by combining logistic regression analysis, Receiver Operating Characteristic (ROC) analysis, Integrated Discrimination Improvement (IDI) analysis and Kaplan-Meier curves. RESULTS: Levels of ITIH1, C3 and S100A6 were significantly associated with the prospective development of rKOA, showing an area under the curve (AUC) of 0.713 (0.624-0.802), 0.708 (0.618-0.799) and 0.654 (0.559-0.749), respectively to predict rKOA in the replication cohort. The inclusion of ITIH1 in the clinical model (age, gender, BMI, previous knee injury and WOMAC pain) improved the predictive capacity of the clinical covariates (AUC = 0.754 [0.670-0.838]) producing the model with the highest AUC (0.786 [0.705-0.867]) and the highest IDI index (9%). High levels of ITIH1 were also associated with an earlier onset of the disease. CONCLUSION: A clinical model including protein biomarkers that predicts incident rKOA has been developed. Among the tested biomarkers, ITIH1 showed potential to improve the capacity to predict rKOA incidence in clinical practice.

Glucosamine and its N-acetyl-phenylalanine derivative prevent TNF-alpha-induced transcriptional activation in human chondrocytes.

OBJECTIVES: Glucosamine (GlcN) is used in the treatment of osteoarthritis as symptomatic slow-acting drug, but its mode of action is not completely known. We analyzed the influence of GlcN and its N-acetyl-phenylalanine derivative (NAPA) on mRNA transcription level of TNF-alpha-stimulated genes in cell culture. METHODS: Human immortalized chondrocyte cell line lbpva55 was stimulated with TNF-alpha and treated with GlcN and NAPA. mRNA transcription level of several genes, identified by complementary DNA microarray (cDNA microarray), was validated by Quantitative Real-Time Polymerase Chain Reaction (Q-RT-PCR). RESULTS: Several genes, whose mRNA level was increased by TNF-alpha treatment and significantly reduced by GlcN and NAPA in lbpva55 cells, were identified. These include cytokine receptors TNF-R1 and TNF-R2, their associated factor TRAF-6, signaling intermediates IGFB-6 and Rnd1, as well as cell cycle regulating proteins CUL-2 and G1S protein 1. Down- regulation of mRNA expression level of some of these genes is in accordance with inactivation of NF-kB transcription factor. Moreover, we found down-regulation of c-jun mRNA level, a component of AP-1 transcription factor. CONCLUSIONS: Our study suggests that GlcN and NAPA interfere with activation of NF-kB and AP-1 transcription factors, which are responsible for the expression of genes involved in diverse biological processes, such as cell growth and death, inflammatory and stress responses, accounting for the beneficial effects of GlcN in osteoarthritis.

Renal-cell carcinoma metastatic to the thyroid. Aspiration cytology and histologic findings.

A case of renal-cell carcinoma metastatic to the thyroid eight years after the removal of the primary tumor is presented, with the aspiration cytologic and histologic findings described. This unusual presentation and the incidence and behavior of renal-cell carcinomas and tumors metastatic to the thyroid are discussed.

A comparison of androgens for anemia in patients on hemodialysis.

To compare the erythropoietic effects of nandrolone decanoate, testosterone enanthate, oxymetholone, and fluoxymesterone, we performed a randomized clinical trial in patients with anemia who were receiving maintenance hemodialysis (the women were not given testosterone enanthate). After a control period of at least two months, patients received one of the drugs for six months and then returned to control status; a second and third drug were administered in a similar fashion. Seventy-seven patients completed the first drug period, 56 the second, and 35 the third. The response to nandrolone and testosterone enanthate, the two drugs given by injection, was clearly superior to the response to oxymetholone or fluoxymesterone, given by mouth, in terms of the percentage of patients responding and the mean rise in hematocrit. Approximately half the patients had an increase of at least 5 percentage points in hematocrit after an injectable androgen was given; more than half the women responded. Patients who required transfusions regularly and those who had bilateral nephrectomies did not respond.