Clinical and ultrasonographic predictors of joint replacement for knee osteoarthritis: results from a large, 3-year, prospective EULAR study.

Objectives: To determine clinical and ultrasonographic predictors of joint replacement surgery across Europe in primary osteoarthritis (OA) of the knee.

Methods: This was a 3-year prospective study of a painful OA knee cohort (from a EULAR-sponsored, multicentre study). All subjects had clinical evaluation, radiographs and ultrasonography (US) at study entry.

Beam hardening correction in CT myocardial perfusion measurement.

This paper presents a method for correcting beam hardening (BH) in cardiac CT perfusion imaging. The proposed algorithm works with reconstructed images instead of projection data. It applies thresholds to separate low (soft tissue) and high (bone and contrast) attenuating material in a CT image.

OCT4A contributes to the stemness and multi-potency of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs).

The OCT4A gene, a POU homeodomain transcription factor, has been shown to be expressed in embryonic stem cells (ESC) as well as hUCB-MSCs. In this study, the roles played by OCT4A in hUCB-MSCs were determined by stably inhibiting OCT4A with lenti-viral vector-based small hairpin RNA (shRNA). A decreased rate of cell proliferation was observed in OCT4-inhibited hUCB-MSCs.

DNA binding site sequence directs glucocorticoid receptor structure and activity.

Genes are not simply turned on or off, but instead their expression is fine-tuned to meet the needs of a cell. How genes are modulated so precisely is not well understood. The glucocorticoid receptor (GR) regulates target genes by associating with specific DNA binding sites, the sequences of which differ between genes.

The unfolded protein response during prostate cancer development.

Accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR). The UPR promotes cell survival by adjusting ER protein folding capacity but if homeostasis cannot be re-established, apoptosis is induced. The execution of life/death decisions is regulated by the three UPR branches (IRE1, PERK, ATF6) and their downstream effectors.

Aortic calcification is associated with aortic stiffness and isolated systolic hypertension in healthy individuals.

Arterial stiffening is an independent predictor of mortality and underlies the development of isolated systolic hypertension (ISH). A number of factors regulate stiffness, but arterial calcification is also likely to be important. We tested the hypotheses that aortic calcification is associated with aortic stiffness in healthy individuals and that patients with ISH exhibit exaggerated aortic calcification compared with controls.

[Effects of community-based case management program for clients with hypertension].

Purpose: The purpose of this study was to analyze effects of a community-based case management program for clients with hypertension living in the community.

Methods: The research design was a one group pre and post-test design with 30 participants with hypertension who agreed to participate in the 8-12 week case management program provided by case managers from the National Health Insurance Corporation in 2002. Data were collected three times, before and after the case management services, and 6 months later.

Inflammatory sciatica due to spinal tophaceous gout.

A 73-year-old woman with chronic tophaceous gout presented with acute right-sided sciatica. Conventional radiology and CT scan of the lumbar spine revealed severe degenerative changes at the level of L3/4 and L4/5 disc and tophaceous deposits around the facet joints bilaterally. Investigations revealed a raised acute phase response (C reactive protein 97 mg/l, erythrocyte sedimentation rate >100 mm/h), leucocytosis and thrombocytosis.

Chemosensitization of gemcitabine-resistant human bladder cancer cell line both in vitro and in vivo using antisense oligonucleotide targeting the anti-apoptotic gene, clusterin.

Objective: To characterize changes in clusterin (sCLU-2) expression in bladder cancer cells after continuous treatment with gemcitabine and to determine whether knockdown of sCLU-2 can re-introduce sensitivity of gemcitabine-resistant cells to treatment with gemcitabine.

Materials And Methods: A human bladder cancer cell line, UM-UC-3, was continuously exposed to increasing doses of gemcitabine in vitro, and a gemcitabine-resistant cell line UM-UC-3R was developed. The role of sCLU-2 in chemoresistant phenotype acquired in both in vitro and in vivo was then analysed using antisense oligonucleotide targeting the sCLU-2 gene (OGX-011).

Paclitaxel incorporated in hydrophobically derivatized hyperbranched polyglycerols for intravesical bladder cancer therapy.

Objective: To develop paclitaxel incorporated into unimolecular micelles based on hydrophobically derivatized hyperbranched polyglycerols (dHPGs) for use as mucoadhesive intravesical agents against non-muscle-invasive bladder cancer.

Materials And Methods: Two different types of dHPGs (HPG- C10-polyethylene glycol (PEG) and polyethyleneimine (PEI)-C18-HPG) were synthesized and paclitaxel was loaded into these using a solvent evaporation method. After physicochemical characterization of the resulting nanoparticles, four human bladder cancer cell lines were incubated with various concentrations of paclitaxel incorporated in dHPGs and the results were compared with those of paclitaxel formulated in Cremophor-EL (Taxol(R), Bristol-Myers-Squibb).

Insulin-like growth factor binding protein-2 is a novel therapeutic target associated with breast cancer.

Purpose: Insulin-like growth factor (IGF) binding proteins (IGFBP) modulate interactions of IGF ligands with the IGF-I receptor. The role of IGFBPs, and specifically IGFBP-2, in breast cancer progression has been poorly defined. This study assesses the effect of IGFBP-2 on the behavior of human breast cancer using clinical specimens as well as in vitro and in vivo experimental systems.

Is Bayh-Dole good for developing countries? Lessons from the US experience.

The US Bayh-Dole Act encourages university patenting of inventions arising from publicly funded research. Lessons from three decades of US experience serve as a cautionary tale for those countries that may choose to emulate Bayh-Dole.

[Dry cough, chest pain and difficult breathing in a patient with rheumatoid arthritis].

Pulmonary involvement is the most frequent extra-articular manifestation of rheumatoid arthritis. The occurrence of a chronic hydro-pneumo-thorax associated with pulmonary nodules is rare. Cavitation of the most superficial nodules and their rupture into the pleural cavity are most likely involved in this complication.

Developments in the scientific and clinical understanding of gout.

Gout is the most common form of inflammatory arthritis in the elderly. In the last two decades, both hyperuricemia and gout have increased markedly and similar trends in the epidemiology of the metabolic syndrome have been observed. Recent studies provide new insights into the transporters that handle uric acid in the kidney as well as possible links between these transporters, hyperuricemia, and hypertension.

Miller-Fisher syndrome in a patient with rheumatoid arthritis treated with adalimumab.

Adalimumab is a frequently prescribed TNFalpha inhibitor for treatment of rheumatoid arthritis. We report on a patient who probably developed a Miller-Fisher syndrome after the second injection of adalimumab.

GLI2 knockdown using an antisense oligonucleotide induces apoptosis and chemosensitizes cells to paclitaxel in androgen-independent prostate cancer.

Purpose: GLI transcription factors mediate hedgehog signaling and have been implicated in several human malignancies, including prostate cancer. The objectives of this study were to characterize GLI2 expression levels in human prostate cancer cell lines and tissues to test the effect of antisense oligonucleotide (ASO) targeting GLI2 on androgen-independent (AI) prostate cancer cell lines.

Experimental Design: A tissue microarray was used to characterize differences in GLI2 expression in benign prostate hyperplasia, prostate cancer treated by neoadjuvant hormonal therapy and AI prostate cancer.

Social experience modifies pheromone expression and mating behavior in male Drosophila melanogaster.

Background: The social life of animals depends on communication between individuals. Recent studies in Drosophila melanogaster demonstrate that various behaviors are influenced by social interactions. For example, courtship is a social interaction mediated by pheromonal signaling that occurs more frequently during certain times of the day than others.

The Canadian Benign Prostatic Hyperplasia Audit Study (CanBas).

Objective: To determine the prevalence, diagnostic patterns and management of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in Canadian urology outpatient practice.

Methods: Representative urologists were randomly selected from lists provided by the Canadian and Quebec Urological Associations. Each patient identified with a BPH diagnosis during a typical 2-consecutive-week period during April, May or June 2007 was asked to complete a corresponding International Prostate Symptom Score (IPSS) questionnaire.

[Oncolytic vesicular stomatitis viruses as intravesical agents against non-muscle-invasive bladder cancer].

Patients with high-risk bladder cancer who do not respond to bacillus Calmette-Guerin (BCG) immunotherapy represent a significant therapeutic challenge. The addition of interferon to BCG has recently evolved as a second-line treatment option; however, many high-grade tumors are nonresponsive to interferon. Thus, replication-competent oncolytic vesicular stomatitis viruses (VSV) that selectively target interferon-refractory tumors are promising intravesical agents.

The role of stress proteins in prostate cancer.

The development of therapeutic resistance, after hormone or chemotherapy for example, is the underlying basis for most cancer deaths. Exposure to anticancer therapies induces expression of many stress related proteins, including small heat shock proteins (HSPs). HSPs interact with various client proteins to assist in their folding and enhance the cellular recovery from stress, thus restoring protein homeostasis and promoting cell survival.

Further evidence for linkage of familial hyperaldosteronism type II at chromosome 7p22 in Italian as well as Australian and South American families.

Background: Familial hyperaldosteronism type II is a hereditary form of primary aldosteronism not attributable to the hybrid CYP11B1/CYP11B2 mutation that causes glucocorticoid remediable aldosteronism (or familial hyperaldosteronism type I). Although genetic defect(s) underlying familial hyperaldosteronism type II have not yet been elucidated, linkage to chromosome 7p22 was previously reported in two Australian families and a South American family with familial hyperaldosteronism type II.

Objective: To seek evidence of linkage to chromosome 7p22 in two Italian families with familial hyperaldosteronism type II based on markers that have already yielded evidence of linkage in one South American and two Australian familial hyperaldosteronism type II families and to assess the combined multipoint logarithm of odds score in these five families (two Australian, two Italian, and one South American).