Pooled safety analysis of diclofenac sodium topical solution 1.5% (w/w) in the treatment of osteoarthritis in patients aged 75 years or older.

Background: This study aimed to determine the safety of diclofenac sodium topical solution 1.5% (w/w) in 45.5% dimethyl sulfoxide (TDiclo) for the treatment of knee or hand osteoarthritis in persons aged 75 years or older.

Coming to terms with nonsteroidal anti-inflammatory drug gastropathy.

Despite well known complications, oral nonsteroidal anti-inflammatory drugs (NSAIDs) remain the most commonly prescribed medications in the US for musculoskeletal disorders such as osteoarthritis. Although there has been a recent focus on the cardiovascular and renal complications associated with these agents, NSAID gastropathy continues to be a particular concern in many patients, especially those at increased risk for serious adverse events, including the elderly. Complicating the diagnosis of NSAID gastropathy is its silent course, which, up to half of the time, is asymptomatic.

Diclofenac sodium topical solution 1.5% w/w with dimethyl sulfoxide compared with placebo for the treatment of osteoarthritis: pooled safety results.

Oral nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2-selective inhibitors are frequently recommended for management of osteoarthritis (OA). However, serious gastrointestinal and cardiovascular systemic adverse events (AEs) are associated with oral NSAIDs and can be treatment limiting. The efficacy of diclofenac sodium topical solution 1.

The NSAID dilemma: managing osteoarthritis in high-risk patients.

For decades, evidence-based data and reported experience have warned that the common chronic oral nonsteroidal anti-inflammatory drug (NSAID) therapy for osteoarthritis (OA) in elderly patients is ultimately dangerous. Elderly patients with OA are at heightened risk for developing serious gastrointestional and cardiovascular adverse events, including gastrointestinal bleeding, myocardial infarction, and stroke. Prescribing NSAIDs, especially in an elderly population, continues to be discouraged because of these significant risks.

Diclofenac topical solution compared with oral diclofenac: a pooled safety analysis.

Background: Topical nonsteroidal anti-inflammatory drug (NSAID) formulations, which produce less systemic exposure compared with oral formulations, are an option for the management of osteoarthritis (OA). However, the overall safety and efficacy of these agents compared with oral or systemic therapy remains controversial.

Methods: Two 12-week, double-blind, double-dummy, randomized, controlled, multicenter studies compared the safety and efficacy profiles of diclofenac topical solution (TDiclo) with oral diclofenac (ODiclo).

Diclofenac sodium topical solution with dimethyl sulfoxide, a viable alternative to oral nonsteroidal anti-inflammatories in osteoarthritis: review of current evidence.

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may offer a safer alternative to their oral counterparts for the management of osteoarthritis. Diclofenac sodium topical solution with dimethyl sulfoxide (TDiclo) was evaluated in five randomized, controlled trials and is indicated for treatment of the signs and symptoms associated with osteoarthritis of the knee. Three studies showed that TDiclo is superior to placebo and vehicle control with respect to pain, physical function, and perception of osteoarthritis symptoms.

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety.

Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy.

Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels.

During endochondral bone development, the first osteoblasts differentiate in the perichondrium surrounding avascular cartilaginous rudiments; the source of trabecular osteoblasts inside the later bone is, however, unknown. Here, we generated tamoxifen-inducible transgenic mice bred to Rosa26R-LacZ reporter mice to follow the fates of stage-selective subsets of osteoblast lineage cells. Pulse-chase studies showed that osterix-expressing osteoblast precursors, labeled in the perichondrium prior to vascular invasion of the cartilage, give rise to trabecular osteoblasts, osteocytes, and stromal cells inside the developing bone.

Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease.

Osteosarcoma is the most common primary malignant tumor of bone. Analysis of familial cancer syndromes and sporadic cases has strongly implicated both p53 and pRb in its pathogenesis; however, the relative contribution of these mutations to the initiation of osteosarcoma is unclear. We describe here the generation and characterization of a genetically engineered mouse model in which all animals develop short latency malignant osteosarcoma.

Mitochondrial DNA mutations in oxyphilic and chief cell parathyroid adenomas.

Background: The potential pathogenetic significance of mitochondrial DNA (mtDNA) mutations in tumorigenesis is controversial. We hypothesized that benign tumorigenesis of a slowly replicating tissue like the human parathyroid might constitute an especially fertile ground on which a selective advantage conferred by mtDNA mutation could be manifested and might contribute to the oxyphilic phenotype observed in a subset of parathyroid tumors.

Methods: We sought acquired mitochondrial DNA mutations by sequencing the entire 16.

Continuous activation of G alpha q in osteoblasts results in osteopenia through impaired osteoblast differentiation.

We explored the role of G alpha(q)-mediated signaling on skeletal homeostasis by selectively expressing a constitutively active G alpha(q) (mutation of Q209L) in osteoblasts. Continuous signaling via G alpha(q) in mouse osteoblastic MC3T3-E1 cells impaired differentiation. Mice that expressed the constitutively active G alpha(q) transgene in cells of the osteoblast lineage exhibited severe osteopenia in cortical and trabecular bones.

A parathyroid myxoadenoma observed grossly.

We are reporting a case of a patient with primary hyperparathyroidism because of an unusual parathyroid adenoma. The tumor had an extensive myxofibrous stroma without an identifiable lipomatous component. Though moderate to extensive myxoid alteration of the stroma has been reported in lipoadenomas, to the best of our knowledge, this is the first parathyroid adenoma in which the myxomatous component was recognized grossly and which lacked a stromal adipose component.

Predictors of an accurate preoperative sestamibi scan for single-gland parathyroid adenomas.

Objective: To investigate why some patients with single parathyroid adenomas have negative preoperative sestamibi scans.

Design: Retrospective review.

Setting: Tertiary care center.

Role of apheresis in rheumatoid arthritis.

Apheresis, a therapeutic procedure that has been available for decades, has recently been added to the long-term management of rheumatoid arthritis (RA). It is a procedure whereby blood is removed from the body and divided into its various components. With the development of specific instrumentation, it has become possible to target the specific cellular or humoral components to be removed or altered.

Gadofluorine-enhanced magnetic resonance imaging of carotid atherosclerosis in Yucatan miniswine.

Objective: The aim of this study was to determine whether gadofluorine, a paramagnetic magnetic resonance imaging (MRI) contrast agent, selectively enhances carotid atherosclerotic plaques in Yucatan miniswine.

Methods: Atherosclerotic plaques were induced in the left carotid arteries (LCA) of Yucatan miniswine (n=3) by balloon denudation and high cholesterol diet. T1-weighted MRI was performed before and 24 hours after gadofluorine injection (at a dose of 100 micromol/kg) to assess the enhancement of the balloon-injured LCA wall relative to healthy, uninjured right carotid artery (RCA) wall.

Regional material property alterations in porcine femoral arteries with atheroma development.

We have developed a novel methodology that permits assessment of regional vascular mechanical property alterations in the presence of atheroma in vivo employing a Yucatan miniswine model with induced lesions. Femoral arteries were imaged with intravascular ultrasound. Image data were segmented and, following three-dimensional reconstruction, underwent finite element and sensitivity analysis with optimization to identify regions with altered vascular mechanical properties.

Porcine carotid arterial material property alterations with induced atheroma: an in vivo study.

Objective: A novel methodology has been developed to evaluate regional alterations in arterial wall material properties with induced atheroma in an animal model.

Methods: Atheromatous lesions (fatty, fibro-fatty, and fibrous) were induced in the carotid arteries of a Yucatan miniswine model by endothelial cell denudation and high cholesterol diet. The images at base line and 8 weeks after denudation were obtained using intravascular ultrasound (IVUS) imaging along with hemodynamic data.

Effects of Prosorba column apheresis in patients with chronic refractory rheumatoid arthritis.

Objective: Since the approval of Prosorba column apheresis therapy (PCT) for rheumatoid arthritis (RA) in 1999 there have been multiple requests for additional information on the response rate of PCT used commercially in rheumatology practice settings.

Methods: Data were collected in a noninterventional prospective fashion on patients with RA who qualified for the PCT treatment per the package insert. There were 91 patients who completed the 12 prescribed treatments.