Time to first and sustained improvement in WOMAC domains among patients with osteoarthritis receiving tanezumab.

Objective: To assess onset of effect in three placebo- or nonsteroidal anti-inflammatory drug (NSAID)-controlled trials of tanezumab in patients with moderate-to-severe osteoarthritis.

Methods: Post-hoc nonparametric Kaplan-Meier analyses were used to estimate median time to first improvement and to sustained improvement in Western Ontario and McMaster Universities Osteoarthritis Index domain (Pain, Physical Function, Stiffness) scores across a range of improvement thresholds (0-100%, in 5% increments). Time to first improvement was defined as the first week scores met the pre-specified threshold.

Single and Composite Endpoints of Within-Patient Improvement in Symptoms: Pooled Tanezumab Data in Patients with Osteoarthritis.

Introduction: Combining measures of key core domains (especially pain and function) into a composite endpoint that requires each patient to meet a threshold of improvement for each domain provides information on multiple aspects of osteoarthritis within individual patients. This pooled analysis of two phase 3 studies (NCT02697773, NCT02709486) explored single and composite endpoints for assessing within-patient improvement in knee or hip osteoarthritis symptoms following subcutaneous administration of tanezumab or placebo.

Methods: Endpoints at week 16 included proportions of responders (≥ 30% improvement) in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function, WOMAC Pain/Function composite, and weekly average pain; and patient acceptable symptom state (PASS) composite responders, minimal clinically important improvement (MCII) composite responders, Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responders, and sustained weekly average pain responders.

General Safety and Tolerability of Subcutaneous Tanezumab for Osteoarthritis: A Pooled Analysis of Three Randomized, Placebo-Controlled Trials.

Objective: This pooled analysis of 3 randomized, placebo-controlled trials (16-24 week treatment and 8-24 week follow-up) assessed safety of subcutaneous tanezumab (2.5-10 mg every 8 weeks) in 1,840 patients with hip or knee osteoarthritis.

Methods: Overall treatment-emergent adverse events (TEAEs) and TEAEs of abnormal peripheral sensation (APS) were prospectively assessed in 3 trials.

Onset and maintenance of efficacy of subcutaneous tanezumab in patients with moderate to severe osteoarthritis of the knee or hip: A 16-week dose-titration study.

Objective: To examine the onset and maintenance of efficacy of subcutaneous tanezumab for pain relief and functional improvement in difficult-to-treat patients with moderate-to-severe osteoarthritis (OA) in a 16-week dose-titration study (NCT02697773).

Methods: Patients were randomized to placebo (placebo group) or tanezumab 2.5 mg at baseline and week 8 (tanezumab 2.

Effect of Tanezumab on Joint Pain, Physical Function, and Patient Global Assessment of Osteoarthritis Among Patients With Osteoarthritis of the Hip or Knee: A Randomized Clinical Trial.

Importance: Patients with osteoarthritis (OA) may remain symptomatic with traditional OA treatments.

Objective: To assess 2 subcutaneous tanezumab dosing regimens for OA.

Design, Setting, And Participants: A randomized, double-blind, multicenter trial from January 2016 to May 14, 2018 (last patient visit).

Efficacy and safety of tanezumab added on to diclofenac sustained release in patients with knee or hip osteoarthritis: a double-blind, placebo-controlled, parallel-group, multicentre phase III randomised clinical trial.

Objectives: Tanezumab, a monoclonal antibody, inhibits nerve growth factor and reduces chronic pain. This randomised, double-blind, controlled multicentre study was conducted to evaluate the efficacy and safety of tanezumab added to oral diclofenac sustained release (DSR) in patients with hip or knee osteoarthritis (OA) pain.

Methods: Patients (N=604) with moderate to severe knee or hip OA tolerating stable DSR were randomised and treated with DSR 75 mg twice daily combined with intravenous tanezumab 10, 5 or 2.

Tanezumab reduces osteoarthritic hip pain: results of a randomized, double-blind, placebo-controlled phase III trial.

Objective: To compare the efficacy of tanezumab versus placebo for reducing pain and improving physical function in patients with osteoarthritis (OA) of the hip.

Methods: This was a 32-week, randomized, double-blind, placebo-controlled, phase III trial. Patients with baseline Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscale scores of ≥5 and ≥4, respectively, and patient's global assessment of OA as "fair," "poor," or "very poor" were treated at baseline and weeks 8 and 16.

Tanezumab reduces osteoarthritic knee pain: results of a randomized, double-blind, placebo-controlled phase III trial.

Unlabelled: The objective of this study was to compare the analgesic efficacy of tanezumab versus placebo in patients with osteoarthritis (OA) of the knee. This was a 32-week, randomized, double-blind, placebo-controlled phase III trial (NCT00733902). The patient criteria included diagnosis of OA; Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscale scores of ≥5 and ≥4, respectively; Patient's Global Assessment of Osteoarthritis (PGA) ≥3; and failure of nonopiate pain medications or candidacy for invasive interventions.

Cloning and characterization of the G protein betagamma subunits from Trichoplusia ni (High Five cells).

Baculoviral-mediated expression in insect cells has become a method of choice where high-level protein expression is desired and where expression in Escherichia coliform (E. coli.) is unsuitable.

Normal hematopoiesis and inflammatory responses despite discrete signaling defects in Galpha15 knockout mice.

Galpha15 activates phospholipase Cbeta in response to the greatest variety of agonist-stimulated heptahelical receptors among the four Gq class G-protein alpha subunits expressed in mammals. Galpha15 is primarily expressed in hematopoietic cells in fetal and adult mice. We disrupted the Galpha15 gene by homologous recombination in embryonic stem cells to identify its biological functions.

Alternate coupling of receptors to Gs and Gi in pancreatic and submandibular gland cells.

Many Gs-coupled receptors can activate both cAMP and Ca2+ signaling pathways. Three mechanisms for dual activation have been proposed. One is receptor coupling to both Gs and G15 (a Gq class heterotrimeric G protein) to initiate independent signaling cascades that elevate intracellular levels of cAMP and Ca+2, respectively.

RGS proteins determine signaling specificity of Gq-coupled receptors.

Regulators of G protein signaling (RGS) proteins accelerate GTP hydrolysis by Galpha subunits, thereby attenuating signaling. RGS4 is a GTPase-activating protein for Gi and Gq class alpha subunits. In the present study, we used knockouts of Gq class genes in mice to evaluate the potency and selectivity of RGS4 in modulating Ca2+ signaling transduced by different Gq-coupled receptors.

Promiscuous coupling of receptors to Gq class alpha subunits and effector proteins in pancreatic and submandibular gland cells.

Mice with deficiencies in one or more Gq class alpha subunit genes were used to examine the role of the alpha subunit in regulating Ca2+ signaling in pancreatic and submandibular gland cells. Western blot analysis showed that these cells express three of the four Gq class subunits, Galphaq, Galpha11, and Galpha14 but not Galpha15. Surprisingly, all parameters of Ca2+ signaling were identical in cells from wild type and four lines of mutant mice: 1) Galpha11-/-, 2) Galpha11-/-/Galpha14-/-, 3) Galpha14-/-/Galpha15-/-, and 4) Galphaq-/-/Galpha15-/-.

Gene structure of murine Gna11 and Gna15: tandemly duplicated Gq class G protein alpha subunit genes.

G protein alpha subunits are encoded by a multigene family of 16 genes that can be grouped into four classes, Gq, Gs, Gi, and G12. The Gq class is composed of four genes in mouse and human, and two of these genes, Gna11 and Gna15, cosegregate on mouse chromosome 10. We have characterized the gene structures of murine Gna11 and Gna15.

Insulin-like growth factor-I blood levels in severely burned patients: effects of time post injury, age of patient and severity of burn.

Objectives: Insulin-like growth factor-I (IGF-I) is a polypeptide growth factor that stimulates protein synthesis. The aims of this study were to determine (1) the effect of a severe burn on blood IGF-I levels and (2) the variables controlling IGF-I level variations during recovery of these hypermetabolic patients.

Patients: Eleven patients, nine men and two women (age range 22-55 years) were studied for 25 days following a severe burn (18-75% of total body surface area, mean 36%).

No change in glucose tolerance and substrate oxidation after a high-carbohydrate, low-fat diet.

Possible changes in glucose tolerance and substrate oxidation after a high-carbohydrate, low-fat diet were studied in seven healthy volunteers. Each subject consumed two experimental diets for 1 week after 1 week on a stabilization diet; diet no. 1 11% fat and 64% carbohydrates, and diet no.

Length of care in patients with severe burns with or without early enteral nutritional support. A retrospective study.

The possible influence of early enteral nutritional support on the length of care was explored retrospectively in 25 patients with burns greater than 20% total body surface area (TBSA). Patients were divided into two groups according to the time of their admission: group 1, from July 1986 to February 1987 (n = 12) and group 2, from July 1987 to January 1988 (n = 13). The only difference in treatment between the two groups was the start of early enteral nutritional support in group 2.

Dietary habits after ileal pouch-anal anastomosis.

Dietary habits of patients who had undergone ileal pouch-anal anastomosis were assessed and correlated with bowel function. Twenty-four well-adapted patients (11 women, 13 men; mean age 32 years) voluntarily entered the study 30 +/- 4 months after closure of the diverting ileostomy. A standardized questionnaire on 108 food items and a 3-day food journal were used in the assessment.