Lessons from tau-deficient mice.

Both Alzheimer's disease (AD) and frontotemporal dementia (FTD) are characterized by the deposition of hyperphosphorylated forms of the microtubule-associated protein tau in neurons and/or glia. This unifying pathology led to the umbrella term "tauopathies" for these conditions, also emphasizing the central role of tau in AD and FTD. Generation of transgenic mouse models expressing human tau in the brain has contributed to the understanding of the pathomechanistic role of tau in disease. To reveal the physiological functions of tau in vivo, several knockout mouse strains with deletion of the tau-encoding MAPT gene have been established over the past decade, using different gene targeting constructs. Surprisingly, when initially introduced tau knockout mice presented with no overt phenotype or malformations. The number of publications using tau knockout mice has recently markedly increased, and both behavioural changes and motor deficits have been identified in aged mice of certain strains. Moreover, tau knockout mice have been instrumental in identifying novel functions of tau, both in cultured neurons and in vivo. Importantly, tau knockout mice have significantly contributed to the understanding of the pathophysiological interplay between Aß and tau in AD. Here, we review the literature that involves tau knockout mice to summarize what we have learned so far from depleting tau in vivo.

New developments in osteoarthritis.

Osteoarthritis (OA) has been a frustrating disease for both the patient and the physician. Its current impact on society is tremendous and rivals that of ischemic heart disease in many regards. As the baby boomers reach late adulthood and the obesity epidemic rages on, OA will assume an even greater impact on society. The current OA armamentarium only reduces pain and perhaps improves function, but has no impact on the disease incidence or progression. Thus, the challenge for researchers to develop disease-modifying OA drugs becomes an issue of paramount importance. Several advances in the understanding of OA pathophysiology have provided a glimpse of optimism that disease modification is a real possibility.

The modified Nail Psoriasis Severity Index: validation of an instrument to assess psoriatic nail involvement in patients with psoriatic arthritis.

OBJECTIVE: Patients with psoriasis and psoriatic arthritis (PsA) commonly have nail involvement. There is no validated psoriatic nail assessment tool. Recently, investigators developed the Nail Psoriasis Severity Index (NAPSI). Beginning with NAPSI, our goal was to validate a psoriatic nail assessment tool for use in clinical trials, and investigate correlations between nail and other PsA features. METHODS: Fingernails of 29 patients with PsA were photographed and scored. Clinical data were collected. Using the original NAPSI, analysis revealed high interrater variability of nail scores. Twenty patients' photographs were regraded using the modified NAPSI (mNAPSI). RESULTS: The mNAPSI scores had excellent interrater reliability (Cronbach's alpha 0.98). Nail scores and physicians' global nail severity visual analog scores showed good inter- and intrarater correlations (Spearman's rho 0.85 and 0.90-0.99, respectively; p < 0.01). Several clinical measures correlated with nail scores. CONCLUSION: The mNAPSI demonstrated excellent interrater reliability and construct validity, and may be a valuable tool.

Validation of American College of Rheumatology classification criteria for knee osteoarthritis using arthroscopically defined cartilage damage scores.

OBJECTIVE: To validate the ability of the American College of Rheumatology (ACR) clinical classification criteria and the ACR clinical plus radiographic classification criteria for osteoarthritis of the knee to predict articular cartilage damage. METHODS: Ninety subjects with knee osteoarthritis (OA) who were enrolled in a prospective study determining the therapeutic efficacy of arthroscopic irrigation were characterized as to whether they fulfilled the ACR clinical classification criteria or the ACR clinical plus radiographic classification criteria. Ten rheumatoid arthritis (RA) patients were included as controls. Cartilage damage was defined using the ACR/Knee Arthroscopy Osteoarthritis Scale (ACR/KAOS) system, which is a validated outcome instrument for knee OA based on arthroscopic visualization. Mean values of the damage scores in each group were calculated and compared by t-test to determine statistical significance between the 3 groups. RESULTS: The mean ACR/KAOS score for the 10 RA patients was 1.8 [SD 1.22; range 0 to 4]. Of the 90 OA patients who underwent arthroscopy, only 73 patients had sufficient videotape to make an accurate assessment by the blinded assessor. The mean ACR/KAOS score for the 6 OA patients who fulfilled only the ACR clinical classification was 17.4 [SD 11.3; range 5 to 34.3] and the mean ACR/KAOS score for the 67 patients who fulfilled the ACR clinical plus radiographic classification criteria was 42.0 [SD 29.1; range 5.1 to 118.4]. These differences were statistically significant (RA versus OA clinical P=0.02; RA versus OA clinical+radiographic P

Calcium-containing crystals and osteoarthritis: implications for the clinician.

The clinical implication of articular deposits of calcium-containing crystals (specifically of calcium pyrophosphate dihydrate and hydroxyapatite) in osteoarthritis is unknown. Recent longitudinal studies have suggested that in some instances calcium crystals are direct participants in cartilage damage, while in other situations they are merely markers of joint damage. Better understanding of the mechanisms of crystal formation, especially in relation to inorganic pyrophosphate regulation, has lead to potential avenues for therapeutic intervention. The current treatment of osteoarthritis associated with calcium-containing crystals should involve nonsteroidal anti-inflammatory drugs, intra-articular steroids, and in resistant cases, joint irrigation can be considered. While preliminary studies suggest the possibility of favorable benefits from colchicine and hydroxycholorquine in this osteoarthritis disease subset, more rigorous studies need to be conducted to establish their roles.

New developments in osteoarthritis.

Osteoarthritis (OA) has been a frustrating disease for both the patient and the physician. Its current impact on society is tremendous, and rivals that of ischemic heart disease in many regards. As the baby boomers reach late adulthood and the obesity epidemic rages on, OA will assume an even greater impact on society. The current OA armamentarium only reduces pain and perhaps improves function, and has no impact on the disease incidence or progression. Thus, the challenge for researchers to develop disease-modifying OA drugs becomes an issue of paramount importance. Several advances in our understanding of OA pathophysiology have provided a glimpse of optimism that disease modification is a real possibility. Appreciation of the local factors involved in OA progression as well as the inflammatory nature in a subset of patients has led to different treatment strategies based on predominant phenotype. Further understanding of the initiating events in cartilage destruction, the relationship between the different pathologic influences, and the role of the chondrocyte in maintaining extracellular matrix homeostasis will be necessary to reveal potential targets of therapy.