Towards a definition of "difference" in osteoarthritis

To assess existing information regarding detectable differences in osteoarthritis (OA), a systematic literature search was conducted up to December 1999. Thirty-three articles were considered methodologically relevant to the definition and categorization of detectable differences in OA. It was determined that the musculoskeletal literature contains a wealth of information that relates to observed changes, much of which is derived from the clinical trials literature, but there have been relatively few methodological studies that have systematically evaluated the nature, categorization, and relevance of the change. Furthermore, most of those that have been published take the perspective of an individual or groups of experts other than that of the patient. This summary of the current literature reveals that the diverse sources of information go part way towards developing an understanding of detectable differences and their importance in the area of OA research and clinical practice. Stakeholders' interests as well as factors that modulate perceptions of importance need to be taken under consideration. In particular, the patient's perspective of the importance of change at an individual level requires further evaluation. This area of clinical research is relatively underdeveloped, but there is considerable opportunity for progress.

The validity and heritability of self-report osteoarthritis in an Australian older twin sample

In order to investigate the genetic and environmental antecedents of osteoarthritis (CA), self-report measures of joint pain, stiffness and swelling were obtained from a population-based sample of 1242 twin pairs over 50 years of age. In order to provide validation for these self-report measures, a subsample of 118 twin pairs were examined according to the American College of Rheumatology clinical and radiographic criteria for the classification of osteoarthritis. A variety of statistical methods were employed to identify the model derived from self-report variables which would provide optimal prediction of these standardised assessments, and structural equation modelling was used to determine the relative influences of genetic and environmental influences on the development of osteoarthritis. Significant genetic effects were found to contribute to osteoarthritis of the hands, hips and knees in women, with heritability estimates ranging from 30-46% depending on the site. In addition, the additive genetic effects contributing to osteoarthritis in various parts of the body were confirmed to be the same. Statistically significant familial aggregation of osteoarthritis in men was also observed, but it was not possible to determine whether this was due to genetic or shared environmental effects.

Cationic drug pharmacokinetics in diseased livers determined by fibrosis index, hepatic protein content, microsomal activity, and nature of drug

The disposition kinetics of six cationic drugs in perfused diseased and normal rat livers were determined by multiple indicator dilution and related to the drug physicochemical properties and liver histopathology. A carbon tetrachloride (CCl4)induced acute hepatocellular injury model had a higher fibrosis index (FI), determined by computer-assisted image analysis, than did an alcohol-induced chronic hepatocellular injury model. The alcohol-treated group had the highest hepatic alpha(1)- acid glycoprotein, microsomal protein (MP), and cytochrome P450 (P450) concentrations. Various pharmacokinetic parameters could be related to the octanol-water partition coefficient (log P-app) of the drug as a surrogate for plasma membrane partition coefficient and affinity for MP or P450, the dependence being lower in the CCl4-treated group and higher in the alcohol-treated group relative to controls. Stepwise regression analysis showed that hepatic extraction ratio, permeability-surface area product, tissue-binding constant, intrinsic clearance, partition ratio of influx (k(in)) and efflux rate constant (k(out)), and k(in)/k(out) were related to physicochemical properties of drug (log P-app or pK(a)) and liver histopathology (FI, MP, or P450). In addition, hepatocyte organelle ion trapping of cationic drugs was evident in all groups. It is concluded that fibrosis-inducing hepatic disease effects on cationic drug disposition in the liver may be predicted from drug properties and liver histopathology.

Body mass index-related human adipocyte agouti expression is sex-specific but not depot-specific

Objective: To determine if human adipocyte agouti signal protein (ASIP) mRNA expression is associated with obesity and is gender and/or depot specific. Research Methods and Procedures: Subjects included 8 men (64 +/- 3 years) and 14 women (56 +/- 15 years) undergoing elective abdominal surgery. ASIP mRNA levels in isolated omental and subcutaneous abdominal adipocytes were measured by quantitative reverse transcription polymerase chain reaction. Results: No significant depot difference was observed between genders; ASIP mRNA levels of omental and subcutaneous abdominal adipocytes were pooled for this analysis. BMI and ASIP gene expression were negatively correlated in men (p = -0.70; p < 0.05), whereas a positive relationship was observed in women (p = 0.48; p < 0.05). No significant difference was observed in age, body weight, body mass index (BMI), and waist circumference between groups. Hip circumference was significantly higher in women than in men (p < 0.05). Also, no significant difference in ASIP mRNA expression was observed between men and women, regardless of the fat depot. Discussion: These results show that men and women of similar age and BMI present similar ASIP mRNA levels in omental and subcutaneous abdominal adipocytes. However, a sexual dimorphism exists in the relationship between ASIP expression and BMI. If ASIP is involved in appetite regulation or energy homeostasis in humans, this observation may contribute to the recognized differences in these parameters between men and women.

Rhythmic variations in pain, stiffness, and manual dexterity in hand osteoarthritis

Objective: To explore circadian variation in pain, stiffness, and manual dexterity inpatients with hand osteoarthritis (OA). Methods: Twenty one patients with hand OA, as defined by ACR criteria (17 women, four men, mean age 62.2 years, range 52-74 years) self rated pain and stiffness on separate 10 cm horizontal visual analogue scales and performed bead intubation coordinometry (BIC) six times each day (on waking up, at bedtime, and every four hours in between) for 10 consecutive days. Each series (using data with the trend removed if there was a significant trend) was analysed for circadian rhythmicity by a cosine. vector technique (single cosinor). With individual data expressed as the percentage of the mean, group rhythm characteristics at period 24 hours were summarised for each variable by population mean cosinor analysis. Results: Individual analyses identified significant circadian rhythms at pless than or equal to0.05 for pain (n=15/21), stiffness (n=16/20), and dexterity (n=18/21), and a significant circadian rhythm on a group basis was identified for pain (p=0.013), stiffness (p

A four-stage index 2 Diagonally Implicit Runge-Kutta method

High index Differential Algebraic Equations (DAEs) force standard numerical methods to lower order. Implicit Runge-Kutta methods such as RADAU5 handle high index problems but their fully implicit structure creates significant overhead costs for large problems. Singly Diagonally Implicit Runge-Kutta (SDIRK) methods offer lower costs for integration. This paper derives a four-stage, index 2 Explicit Singly Diagonally Implicit Runge-Kutta (ESDIRK) method. By introducing an explicit first stage, the method achieves second order stage calculations. After deriving and solving appropriate order conditions., numerical examples are used to test the proposed method using fixed and variable step size implementations. (C) 2001 IMACS. Published by Elsevier Science B.V. All rights reserved.

Investigation of hip abductor activation in subject with clinical unilateral hip osteoarthritis

Objectives: (a) To compare the magnitude of gluteus medius and tensor fascia lata activation between a group of subjects with clinical unilateral hip osteoarthritis and a group of healthy older adults. (b) To compare the magnitude of activation of the gluteus medius and tensor fascia lata between sides in a group of subjects with clinical unilateral hip osteoarthritis and a group of healthy older adults. Methods: 19 subjects with clinical unilateral hip osteoarthritis and 19 healthy controls were investigated. The subjects performed a stepping task during which recordings were obtained using surface electromyograms from the hip abductors, and kinetic data were obtained from a dual force platform. Results: Subjects with clinical hip osteoarthritis had higher gluteus medius activation than the healthy older adults (p=0.037). In addition, there were no differences in the magnitude of gluteus medius activation between the sides (p=0.733). There was no difference in the force platform data between the groups (p=0.078). Conclusions: The increased magnitude of gluteus medius activation in the group with hip osteoarthritis is evidence of a muscular dysfunction associated with hip disease. This has implications for the progressive nature of the disease and for its conservative management.

Impact of osteoarthritis on individuals and society: how much disability? Social consequences and health economic implications

Osteoarthritis is a major cause of disability in both the developed and developing world. With the population aging, the prevalence of osteoarthritis is increasing and its consequences are impacting significantly on society. This is one of the reasons why osteoarthritis has been adopted as a major focus (along with osteoporosis, rheumatoid arthritis, back pain, and musculoskeletal trauma) by the global initiative-the Decade of Bone and Joint Disease. Adequate studies on the costs of osteoarthritis are urgently required so that cogent arguments can be made to governments to appropriately fund prevention and treatment programs for this condition. Its recognition as a major cause of disability, particularly in the aging population, should increase community focus on this important condition. (C) 2002 Lippincott Williams Wilkins, Inc.