The use of glucosamine therapy in osteoarthritis.

Glucosamine products have been used extensively for the management of pain in osteoarthritis. This paper reviews the most recent clinical and experimental studies regarding its efficacy and safety. Although clinical trials include methodologic flaws and publication bias, glucosamine is likely an effective therapy for the symptomatic management of osteoarthritis.

Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms.

Chronic infection with the hepatitis B virus (HBV) is a major risk factor for development of hepatocellular carcinoma (HCC). The pathogenesis of cancer in HBV infection has been extensively analyzed, and multiple factors appear to play a role. A major factor is chronic inflammation and the effects of cytokines in the development of fibrosis and liver cell proliferation.

The role of IL-12, IL-23 and IFN-gamma in immunity to viruses.

IL-12, IL-23 and IFN-gamma form a loop and have been thought to play a crucial role against infectious viruses, which are the prototype of "intracellular" pathogens. In the last 10 years, the generation of knock-out (KO) mice for genes that control IL-12/IL-23-dependent IFN-gamma-dependent mediated immunity (STAT1, IFN-gammaR1, IFNgammaR2, IL-12p40 and IL-12Rbeta1) and the identification of patients with spontaneous germline mutations in these genes has led to a re-examination of the role of these cytokines in anti-viral immunity. We here review viral infections in mice and humans with genetic defects in the IL-12/IL-23-IFN-gamma axis.

Use of well-defined HIV-derived epitopes to evaluate CD4(+) and CD8(+) T cell responses in patients with chronic HIV-1 infection treated with HAART.

Highly active antiretroviral therapy (HAART) is associated with a dramatic clinical benefit to HIV-infected patients through significant plasma viremia reduction and CD4(+) T cells increase. In previous reports, HIV-specific CD4(+) and/or CD8(+) T cell responses have been studied separately during HAART; therefore the relationship between these two virus-specific populations is currently not well understood. In this study, both HIV-specific CD4(+) and CD8(+) T cell responses were investigated using a large panel of well-defined T cell epitope peptides in 24 HIV-1-infected patients undergoing HAART, with undetectable viral load and CD4(+) T cell count >/= 350/mm(3).

When a DMARD fails, should patients switch to sulfasalazine or add sulfasalazine to continuing leflunomide?

Objective: To evaluate the efficacy and safety of adding sulfasalazine to leflunomide treatment compared with switching to sulfasalazine alone in patients with RA with an inadequate response to leflunomide monotherapy.

Methods: Patients with active RA ((DAS28) >3.2) who were enrolled in the first open label phase of the RELIEF study received leflunomide for 24 weeks.

Paracetamol in osteoarthritis of the knee.

Background: Paracetamol is a recommended symptomatic treatment of osteoarthritis (OA), but in clinical trials sample sizes have been relatively small and variable daily doses of paracetamol have been used.

Objectives: To determine the therapeutic efficacy of paracetamol in OA of the knee and identify predictive factors of clinical response to treatment.

Methods: A double blind, parallel group, placebo controlled trial of analgesic efficacy and safety of paracetamol versus placebo including 779 patients with OA of the knee.

Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study.

Objective: To determine prognostic factors for remission in early rheumatoid arthritis.

Methods: 191 patients with rheumatoid arthritis whose disease duration was less than one year were followed up prospectively for five years. Remission, defined by a disease activity score (DAS) of <1.

Efficacy of risedronate on clinical vertebral fractures within six months.

Objective: Postmenopausal osteoporotic women with pre-existing or new incident vertebral fractures are at high risk for future fracture, so prompt treatment is warranted. Risedronate has been shown to reduce the incidence of radiographically-defined vertebral fractures by approximately two-thirds within 1 year.

Research Design: This study examined the effects of risedronate treatment on the time course of the reduction in the risk of clinical vertebral fractures (i.

OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited.

Background: The OARSI Standing Committee for Clinical Trials Response Criteria Initiative had developed two sets of responder criteria to present the results of changes after treatment in three symptomatic domains (pain, function, and patient's global assessment) as a single variable for clinical trials (1). For each domain, a response was defined by both a relative and an absolute change, with different cut-offs with regard to the drug, the route of administration and the OA localization.

Objective: To propose a simplified set of responder criteria with a similar cut-off, whatever the drug, the route or the OA localization.

Management of acute dyspnoea: use and feasibility of brain natriuretic peptide (BNP) assay in the prehospital setting.

Study Objectives: Diagnosis of acute left ventricular failure (LVF) is often difficult in the prehospital setting. Brain natriuretic peptide (BNP) is a marker of LVF. The object of this study was to evaluate the feasibility of BNP measurement during the prehospital management of patients with dyspnoea.

Combination therapy in early rheumatoid arthritis.

The course of rheumatoid arthritis (RA) is determined early and the goals in early RA are to prevent radiologic joint degradation and to achieve optimal clinical and biological remission. Achieving these goals means that many RA patients may be candidates for combination disease-modifying therapy. We review data from randomized clinical trials regarding the impact of these treatment strategies as the initial therapy in early RA.

Interleukin-8 mRNA in vaginal secretions: a prenatal marker of congenital infection in case of preterm labor with intact membranes.

Objective: To study whether interleukin-8 (IL-8) mRNA in vaginal secretions is associated with congenital infection and preterm delivery in the case of preterm labor with intact membranes.

Methods: This prospective clinical study in a tertiary referral center included 280 patients who gave birth to 360 infants from 1997 through 1999. IL-8 mRNA in vaginal secretions was determined with reverse transcriptase polymerase chain reaction.

Efficacy and safety of leflunomide and predisposing factors for treatment response in patients with active rheumatoid arthritis: RELIEF 6-month data.

Objective: The RELIEF investigation was a 48-week, multicenter, international study comprising 2 phases. Results from the first phase, a 24-week open-label cohort study that evaluated the safety and efficacy of leflunomide, as well as predisposing factors to treatment response, are reported here.

Methods: Patients received leflunomide 100 mg once daily for 3 days, followed by 20 mg once daily thereafter.

Neuronal expression of enhanced green fluorescent protein directed by 5' flanking sequences of the rat aldolase C gene in transgenic mice.

The rat aldolase C gene encodes a glycolytic enzyme strongly expressed in adult brain. We previously reported that a combination of distal and proximal 5' flanking sequences, the A + C + 0.8 kilobase (kb) pairs fragments, ensured high brain-specific expression in vivo (Skala et al.

The use of glucosamine therapy in osteoarthritis.

Glucosamine products have been used extensively for the management of pain in osteoarthritis. This paper reviews the most recent clinical and experimental studies regarding its efficacy and safety. Although clinical trials include methodologic flaws and publication bias, glucosamine is likely an effective therapy for the symptomatic management of osteoarthritis.

The role of CCK2 receptors in the homeostasis of the opioid system.

The overlapping distribution of opioid and cholecystokinin (CCK) peptides and their receptors (mu- and delta-opioid receptors, CCK1 and CCK2 receptors) in the central nervous system have led to a large number of studies aimed at clarifying the functional relationships between these two neuropeptides. The existence of regulatory loops between both systems has been proposed, and the physiological antagonism between CCK, through activation of CCK2 receptors, and endogenous opioid systems has been demonstrated. This is illustrated by the large potentiation of the main pharmacological effects of exogenous (morphine) or endogenous (enkephalins) opioids.

Laterally elevated wedged insoles in the treatment of medial knee osteoarthritis. A two-year prospective randomized controlled study.

Objective: To compare the clinical effects of laterally wedged insoles and neutrally wedged insoles (used as control) in patients with medial femoro-tibial knee osteoarthritis.

Study Design: 24-month prospective randomized controlled study.

Patients: Outpatients with painful medial femoro-tibial knee osteoarthritis.

INS VNTR is a QTL for the insulin response to oral glucose in obese children.

We performed a genotype-phenotype association study to examine whether the insulin VNTR (INS VNTR) polymorphism located in the insulin gene promoter was associated with changes in insulin response to oral glucose. Two classes of INS VNTR alleles are observed in Caucasians, the "short" class I and the "long" class III. Plasma insulin and glucose concentrations and indices of insulin secretion (IGI) and sensitivity (ISI) were measured using an oral glucose tolerance test (OGTT) in 387 obese children aged 12 +/- 0.

Sacral inflammatory pseudotumor revealed by paraneoplastic syndrome.

There is still debate on whether inflammatory pseudotumor should be considered benign or malignant. This lesion has only been reported twice in bone, apart from cases complicating foreign body reaction to joint replacement arthroplasty. We report here a third case, localized at the sacrum.

Comparison of the responsiveness of symptomatic outcome measures in knee osteoarthritis.

Objective: A number of international scientific societies have recommended a core set of domains to be systematically assessed in clinical research studies on osteoarthritis (OA), i.e., pain, function, and patient's overall assessment.

Interaction between cyclooxygenase and the renin-angiotensin-aldosterone system: rationale and clinical relevance.

Increased understanding of pathophysiological mechanisms of cardiovascular diseases has shown that the renin-angiotensin-aldosterone system (RAAS) is activated in this setting and suggests a central role for the angiotensin-converting enzyme (ACE). ACE transforms angiotensin I (Ang I) to angiotensin II (Ang II), and also promotes the degradation of bradykinin into inactive metabolites. These bradykinins stimulate nitric oxide synthesis and vasodilatator prostaglandin synthesis via a cyclooxygenase (COX) pathway.

Risks versus benefits of NSAIDs including aspirin in myocarditis: a review of the evidence from animal studies.

NSAIDs, including aspirin (acetylsalicylic acid), are frequently used and effective in a broad variety of inflammatory diseases, i.e. rheumatic carditis and pericarditis.

Bone mineral measurements in mice: comparison of two devices.

Animal models are widely used to explore the pathogenesis and management of osteoporosis. Mice are increasingly being used in animal models. We have evaluated the precision, accuracy, and ability to monitor changes in bone mineral measurements of mice with the Piximus and Hologic QDR 2000 devices.