Search

Studies indicate that allergy sufferers remain dissatisfied with available antiallergic therapies. A new convenient formulation of solubilized steroid combined in the same nasal spray solution with antihistamine may provide added symptom relief. The objective was to evaluate effects of CDX-947 (solubilized budesonide) and CDX-313 (solubilized azelastine + budesonide) against their suspension-type comparators (budesonide [Rhinocort Aqua {RA}] or azelastine + budesonide [Astelin] {AS} + RA]) and placebo on nasal allergy symptoms of patients exposed to controlled levels of ragweed pollen in an environmental exposure chamber (EEC). Two separate EEC studies that enrolled 173 patients were analyzed. Total nasal symptom score (TNSS) and onset of action were captured. Mean change from baseline of TNSS was compared with analysis of covariance and the onset of action determined. Meta-analysis was performed to allow cross-comparisons between studies. All active treatments significantly reduced TNSS when compared with placebo and both CDX-947 and CDX-313 showed increased improvement over the suspension-type comparators. CDX-313 provided significantly faster onset of action for itchy nose and sneezing. No clinically significant adverse events were reported in this study. The novel combination product, CDX-313, provided fast, long-lasting relief for allergic rhinitis symptoms. Compared with products where corticosteroid remains suspended, the new solubilized nasal spray formulation provides added benefit including faster onset of action and superior, convenient dosing of two therapeutics in one convenient product.

Objective: To investigate whether any of 14 serum and urine molecular markers (MMs) used to monitor osteoarthritis (OA) would be associated with particular clinical end-points., Design: Thirty-nine OA patients were bled and urine collected at five time points: at baseline visit and at visits 1, 3, 6 and 12 months later. Twelve clinical measurements were made and the concentrations of each of 14 MMs were determined. Principal component analysis, stepwise linear regression with backward elimination, and logistic regression were used to determine the correlations between MMs and clinical measures., Results: Principal component analysis was used to reduce the 12 clinical measurements into three independent clinical clusters: baseline clinical assessments, changes in clinical assessments and signal joint measurements. The 14 MMs were similarly reduced to five MM clusters. Each of the three clinical clusters was correlated with a single but different MM cluster. Baseline clinical assessments were correlated with bone markers typified by hydroxylysyl pyridinoline (HP) crosslinks, swelling of the signal joint was correlated with inflammation markers, especially CRP, and the change in clinical assessments over the 1 year evaluation was correlated with TGFbeta1. There was no correlation between any of the skeletal markers and the clinical measures, a situation which draws attention to the need for a direct assessment of cartilage damage in OA to validate the use of cartilage markers., Conclusions: This study demonstrates statistical methodology for analysis of clinical trials using multiple MMs and clinical end-points. The patient numbers are sufficient to test hypotheses of relationships of single MMs such as CRP, TGFbeta1 and HP to clinical measures, but larger clinical trials are needed to validate hypotheses., (Copyright 2001 OsteoArthritis Research Society International.)

Objective: To investigate the relationships between serum and urinary molecular markers (MM) used to monitor osteoarthritis., Design: Forty osteoarthritis patients had blood and urine collected at baseline and 1, 3, 6 and 12 months later. Specimens from 20 controls were obtained twice at a one month interval. The concentration of 14 different markers was determined at each time point and the data were analyzed by statistical methodology., Results: The markers could be divided by the method of principal components analysis into five clusters of related markers: inflammation markers (C-reactive protein, tumor necrosis receptor type I and tumor necrosis receptor type II, interleukin 6, eosinophilic cationic protein), bone markers (bone sialoprotein, hydroxylysyl pyridinoline, lysyl pyridinoline), putative markers of cartilage anabolism (carboxypropeptide of type II procollagen, hyaluronan, epitope 846) and catabolism (keratan sulfate, cartilage oligomeric matrix protein), and transforming growth factor beta. Three markers (tumor necrosis factor receptor II, cartilage oligomeric matrix protein and epitope 846) from independent clusters discriminated osteoarthritis patients from controls. Inflammation was not a confounding factor in measurement, but a recognizable distinguishing factor in osteoarthritis., Conclusions: The markers separated into rational groups on the basis of their covariance, a finding with independent biochemical support. The covariance of markers from the same cluster suggests the use of a representative marker from the cluster to reflect changes in osteoarthritis. If multiple markers are being measured within a single cluster, then the use of a weighted cluster 'factor' may be preferable to the separate use of individual markers.

Objective: To compare the effects of tenidap and piroxicam on acute-phase protein and cytokine levels in the blood of rheumatoid arthritis (RA) patients and to explore their associations with clinical disease activity., Methods: A double-blind, randomized, crossover trial in 49 patients with active RA compared 6 weeks of treatment with tenidap (120 mg/day) versus 6 weeks of treatment with piroxicam (20 mg/day)., Results: Median values for C-reactive protein (CRP), Westergren erythrocyte sedimentation rate (ESR), serum amyloid A (SAA) protein, and interleukin-6 (IL-6) were significantly lower after tenidap treatment compared with piroxicam treatment, even in the presence of stable background treatment with prednisone, methotrexate, or prednisone plus methotrexate. The median within-patient treatment differences (after tenidap minus after piroxicam) in the CRP, ESR, SAA, and IL-6 values were -1.7 mg/dl, -10.0 mm/hour, -22.0 micrograms/ml, and -3.7 pg/ml, respectively, and represent -60.4%, -17.7%, -35.5%, and -26.1% of the respective baseline levels. IL-6 levels were positively correlated with CRP and SAA. Plasma IL-1 beta was generally below the level of detection. Tumor necrosis factor alpha levels were similar after tenidap and after piroxicam. Treatment differences for 4 of 7 clinical parameters favored tenidap, but did not reach statistical significance. IL-6, CRP, and ESR were significantly correlated with clinical treatment differences. Tenidap and piroxicam toleration were similar, although tenidap-treated patients exhibited a reversible increase in urinary protein excretion., Conclusion: Tenidap was differentiated from piroxicam by lower levels of acute-phase proteins, ESR, and IL-6 after tenidap treatment. These treatment differences were significantly correlated with clinical parameters.

The enthalpies for the dissolution of lecithin by sodium salts of cholic, deoxycholic, and chenodeoxycholic acids and their glycine and taurine conjugates are reported. Exothermic enthalpies were found in each case. It is suggested that heat evolution is due to a bile salt-lecithin interaction other than hydrophobic interactions. These results provide strong support for the "mixed disk" model for the complex lecithin-bile salt micelle, which requires that a substantial fraction of the bile salt molecules be incorporated within a lecithin bilayer where hydrogenbonded pair formation can occur. Calorimetric studies of the interaction between sodium cholate and nonionic, cationic, and anionic detergents yielded exothermic heats. These results suggest that these bile salt molecules partition into the detergent micelle interior as hydrogenbonded pairs.