Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens.

OBJECTIVE: To determine if the dietary supplements, glucosamine and/or chondroitin, result in reduced joint space narrowing (JSN) and pain among people with symptomatic knee osteoarthritis. METHODS: A double-blind randomised placebo-controlled clinical trial with 2-year follow-up. 605 participants, aged 45-75 years, reporting chronic knee pain and with evidence of medial tibio-femoral compartment narrowing (but retaining >2 mm medial joint space width) were randomised to once daily: glucosamine sulfate 1500 mg (n=152), chondroitin sulfate 800 mg (n=151), both dietary supplements (n=151) or matching placebo capsules (n=151). JSN (mm) over 2 years was measured from digitised knee radiographs. Maximum knee pain (0-10) was self-reported in a participant diary for 7 days every 2 months over 1 year. RESULTS: After adjusting for factors associated with structural disease progression (gender, body mass index (BMI), baseline structural disease severity and Heberden's nodes), allocation to the dietary supplement combination (glucosamine-chondroitin) resulted in a statistically significant (p=0.046) reduction of 2-year JSN compared to placebo: mean difference 0.10 mm (95% CI 0.002 mm to 0.20 mm); no significant structural effect for the single treatment allocations was detected. All four allocation groups demonstrated reduced knee pain over the first year, but no significant between-group differences (p=0.93) were detected. 34 (6%) participants reported possibly-related adverse medical events over the 2-year follow-up period. CONCLUSIONS: Allocation to the glucosamine-chondroitin combination resulted in a statistically significant reduction in JSN at 2 years. While all allocation groups demonstrated reduced knee pain over the study period, none of the treatment allocation groups demonstrated significant symptomatic benefit above placebo. TRIAL REGISTRATION CLINICALTRIALSGOV IDENTIFIER: NCT00513422; http://www.clinicaltrials.gov.

Clinical risk factors associated with radiographic osteoarthritis progression among people with knee pain: a longitudinal study.

BACKGROUND: The aim of this study was to identify modifiable clinical factors associated with radiographic osteoarthritis progression over 1 to 2 years in people with painful medial knee osteoarthritis. METHODS: A longitudinal study was conducted within a randomised controlled trial, the "Long-term Evaluation of Glucosamine Sulfate" (LEGS study). Recruitment occurred in 2007-2009, with 1- and 2-year follow-up assessments by blinded assessors. Community-dwelling people with chronic knee pain (≥4/10) and medial tibiofemoral narrowing (but retaining >2mm medial joint space width) on radiographs were recruited. From 605 participants, follow-up data were available for 498 (82%, mean [sd] age 60 [8] years). Risk factors evaluated at baseline were pain, physical function, use of non-steroidal anti-inflammatory drugs (NSAIDs), statin use, not meeting physical activity guidelines, presence of Heberden's nodes, history of knee surgery/trauma, and manual occupation. Multivariable logistic regression analysis was conducted adjusting for age, sex, obesity, high blood pressure, allocation to glucosamine and chondroitin treatment, and baseline structural disease severity (Kellgren and Lawrence grade, joint space width, and varus alignment). Radiographic osteoarthritis progression was defined as joint space narrowing ≥0.5mm over 1 to 2 years (latest follow-up used where available). RESULTS: Radiographic osteoarthritis progression occurred in 58 participants (12%). Clinical factors independently associated with radiographic progression were the use of NSAIDs, adjusted odds ratios (OR) and 95% confidence intervals (CI) 2.05 (95% CI 1.1 to 3.8), and not meeting physical activity guidelines, OR 2.07 (95% CI 0.9 to 4.7). CONCLUSIONS: Among people with mild radiographic knee osteoarthritis, people who use NSAIDs and/or do not meet physical activity guidelines have a greater risk of radiographic osteoarthritis progression. TRIAL REGISTRATION: ClinicalTrials.gov , NCT00513422 . This original study trial was registered a priori, on August 8, 2007. The current study hypothesis arose before inspection of the data.

Optimizing physician handover through the creation of a comprehensive minimum data set.

Handover is defined as the communication of information between individuals and teams of healthcare providers to support the transfer of patient care and maintain professional responsibility and accountability. Poor handovers are increasingly recognized as potentially dangerous for patient safety and are associated with adverse events. One suggested method to improve the timely and efficient exchange of clinical information at handover and to reduce discontinuities in care is through the use of a minimum data set (MDS). The objective of this study was to describe the process of developing a single comprehensive hospital-wide MDS, created through an analysis of current handover processes and customary information tools used to support physician handover (MDHO) at a large quaternary care pediatric academic health sciences centre. A 20-item questionnaire was administered in person to a senior resident or fellow on each of 49 services identified to objectively assess MDHO processes, including frequency, consistency, format, participants and duration, for each service. The presence, type, location, responsibility for updating and security characteristics of MDHO tools used to support MDHO were also analyzed. The MDHO tools currently in use were collected and analyzed to create a comprehensive cross-institutional MDS. The analysis indicates that MDHO is highly consistent in terms of frequency, processes, participants, duration and the use of written tools to guide information exchange across departments. However, many best practice recommendations for MDHO are not being followed. Further, many of the existing MDHO tools in use have a similar content structure and already contain a majority of the components of a comprehensive MDS. Current local consistency in practice will allow for improved acceptance and adoption of an MDHO tool that continues to meet the clinical and administrative needs of physicians but also addresses needs for data accuracy and security. These additional specifications can be met through the use of information communication technologies.

Arsenic-containing hydrocarbons: natural compounds in oil from the fish capelin, Mallotus villosus.

Arsenic-containing hydrocarbons have been identified for the first time as natural components of fish oil.

Degradation of arylarsenic compounds by microorganisms.

Microorganisms were not directly accumulated when soil contaminated to about 0.5 mM with diphenylarsinic acid (DPAA) was used as the sole source of carbon. However, using toluene as the carbon source yielded several isolates, which were then used in cultivation with DPAA as the sole source of carbon. By these methods, Kytococcus sedentarius strain NK0508, which can grow in up to 0.038 mM DPAA, was isolated. The toxicity of DPAA retarded the growth of K. sedentarius and the direct accumulation of DPAA-utilizing microorganisms from environmental samples. This strain can utilize about 80% of DPAA and phenylarsonic acid as the sole source of carbon for 3 days. Degradation products of DPAA were determined to be cis, cis, muconate and arsenic acid. When K. sedentarius was cultivated with methylphenylarsinic acid and diphenylmethylarsine, about 90% and 10% degradation of the two compounds, respectively, were observed. Diphenylmethylarsine oxide, possibly synthesized by methylation of DPAA, was detected as one of the transformation products. These results suggest that degradation is initiated by splitting of the phenyl groups from the arylarsenic compounds with subsequent hydroxylation of the phenyl groups and ring opening to yield cis, cis, muconate.

Seronegative spondyloarthropathy--studies from the Asia Pacific region.

Recent therapeutic advances, in particular the use of anti-tumour necrosis factor (anti-TNF) agents, have revived interest in the seronegative spondyloarthropathies (SpA), a group of arthritides characterised by axial skeletal involvement and the absence of rheumatoid factor. The purpose of this article is to review the studies that have been done in the Asia Pacific region, as a broad understanding of the scope and severity of this group of diseases would enable rheumatologists and physicians in this part of the world to better manage their patients. The majority of genetic studies have focused on the associations of HLA-B27 with ankylosing spondylitis (AS) and SpA, while a few studies examined the associations of the CARD, IL-1, LMP2, TAP and TGF with AS. There are a handful of studies on the immunological responses to bacteria and cytokine levels in AS. The onset and clinical features of SpA have been reported from most countries in the region, but no data on patient outcomes, using current measurement tools such as the Bath Ankylosing Spondylitis Disease Activity index (BASDAI), is available. Validation of these instruments of measurement as well as classification criteria in different ethnic populations is necessary where no prior data exist. Future studies will likely be focused on better clinical characterisation of patient cohorts, particularly with regard to the use of currently used measurement tools for disease activity and spinal function and mobility, and the identification of the need for biologic therapy in each country.

Power Doppler ultrasound in musculoskeletal disease: a systematic review.

OBJECTIVE: To evaluate the performance characteristics of power Doppler ultrasound as a diagnostic and monitoring tool in the assessment of musculoskeletal disease through a systematic review of the literature. SEARCH STRATEGY: We performed a literature search of PUBMED (1966 to June 2005). SELECTION CRITERIA: Only original research reports written in English involving musculoskeletal disease and power Doppler ultrasound were included. Reviews were noted but not included. Data Extraction/Reporting: The design, subjects, methods, imaging protocols, and performance characteristics studied in the research papers were reported. RESULTS: Of 3568 identified reports, 139 involved power Doppler ultrasound of the musculoskeletal system. Fifty-three of these reports met the inclusion criteria. Ultrasound machine settings were specified in 63% of reports. Rheumatoid arthritis was the most commonly studied musculoskeletal disease (64% of papers). Validity was the most studied performance characteristic (94% of reports), while reliability and responsiveness were studied in 17 and 34%, respectively. CONCLUSIONS: Although the majority of research reports of power Doppler ultrasound assessment of the musculoskeletal system evaluated validity, less than half reported reliability and responsiveness. Further work is needed to evaluate power Doppler ultrasound assessment of the musculoskeletal system before it can be used to guide clinical decisions or be used as an endpoint in clinical trials.

Aerial oxidation of the glucocorticoid side-chain under pH control.

The outcome of aerial oxidation of the glucocortico-steroid side-chain (as exemplified by dexamethasone) has been shown to be subject to strict pH control. At pH 7.4 the glyoxal is the only product; at pH values of 8 and 9.2 the etioacid is formed, and at pH values of 13 or above the epimeric glycolic acids are produced. The glycolic acid epimer that predominates by a factor of 2 and is more stable has been shown by an X-ray crystal structural analysis to be the 20R compound. The presence of arsenite changes the course of the reaction and only the glycolic acids are yielded at pH values of 8 and above.

Degradation of dioxins by cyclic ether degrading fungus, Cordyceps sinensis.

Use of the cyclic ether degrading fungus, Cordyceps sinensis strain A to degrade dibenzo-p-dioxin (DD), 2,3,7-trichlorodibenzo-p-dioxin (2,3,7-triCDD) and octachlorodibenzo-p-dioxin (octaCDD) has revealed a new degradation pathway for dioxins. Catechols and other possible degradation products were synthesized to facilitate the identification, detection and quantification of these products, and phenylboronate was used for the derivatization and analysis of dihydroxylated degradation products. Degradation of DD yielded catechol, which was further metabolized to cis,cis-muconate. 2,3,7-triCDD yielded mono- and dichloro-catechol as well as catechol itself; and the cis,cis-muconates were also detected. octaCDD gave mono- to trichloro-catechol as well as catechol, and the cis,cis-muconates were also found. For all tested dioxin samples dechlorination resulted in replacement of chlorine with hydrogen, and no hydroxylation was observed. It appeared that dechlorination may occur in the degradation of octaCDD to catechols and possibly in the subsequent degradation of chlorinated catechols and/or chlorinated cis,cis-muconates to further breakdown products.

Structural requirements for the interaction of 91 hydroxylated polychlorinated biphenyls with estrogen and thyroid hormone receptors.

Estrogenic and thyroid activities of 91 monohydroxylated PCBs were measured with two-hybrid assays using yeast cells containing the human estrogen receptor ERalpha or human thyroid receptor TRalpha. Estrogenic activity of 30 of the 91 compounds, including all compounds active in the yeast two-hybrid assay, were also measured by a reporter gene assay employing Chinese hamster ovary cells. The mammalian cell assay was more sensitive than the yeast assay but the rank order of estrogenicities of the compounds were in broad agreement for the two assays. Results for estrogenicity and thyroid activity were analyzed by inspection and those for estrogenicity by a theoretical treatment. Inspection indicated para-hydroxyl was more likely to be estrogenically active than meta-, which was more likely to be active than ortho-; one ortho-chlorine was important for activity but additional ortho-chlorines did not increase activity; and 2 lateral chlorines or 2,4,6-chloro- substitution of the non-phenol ring were favorable. In contrast, thyroid activity appeared not to depend strongly on the position of the hydroxyl group although ortho-hydroxyls occurred in the most active compounds. Activity was usually associated with at least one ortho-chlorine, with 2 chlorines in the phenolic ring and, importantly, two chlorines in the non-phenolic ring, and with 1 or 2 chlorines ortho to the hydroxyl group. Examination of the torsion angle between the rings, in the theoretical examination of estrogenicity, suggested that perpendicular orientation (i.e., rigidity) was not essential for activity. Intramolecular hydrogen bonding of the phenolic groups to adjacent chlorines or to the pi-electron cloud of the non-phenol ring possibly decreased activity--the hydroxyl should be free of intramolecular interactions for maximum activity. It was difficult to predict the estrogenic activity of a congener from its obtained potential energy curve (PEC). In general, estrogenically active congeners had large values for the sum of the atomic charges on the carbon atoms of the hydroxylated ring, and on the oxygen atom. Hydroxyl substitution at the para-position allowed the compounds to become more polarizable in the x-axis (molecular axis), whereas OH substitution at the ortho-position made the congeners less polarizable in the same direction. However, no general statement about polarizability and estrogenic activity was possible.

Deuterium exchange in arsenobetaine and dimethylarsinoylacetic acid.

Arsenobetaine occurs naturally in almost all marine animals and it is assumed to be the unreactive end-product of a detoxification pathway. To investigate the properties of arsenobetaine and its likely immediate biogenic precursor, dimethylarsinoylacetic acid, we studied the exchanges of the C-2 methylene protons of these compounds in D2O solution and showed them to be pH dependent first-order reactions. For arsenobetaine, the rate of exchange was highest at high pH values although exchange also occurred at low pH values. For dimethylarsinoylacetic acid, the rate was highest at low pH values although there was also exchange at high pH values. The half-life of the reaction was maximum for arsenobetaine at pH values of 5-6, and for dimethylarsinoylacetic acid at 6.5-8.5. Mechanisms are suggested for the exchange reactions involved.

Microbial treatment of bis (2-ethylhexyl) phthalate in polyvinyl chloride with isolated bacteria.

In this study, we investigated the use of microbes to degrade and remove bis (2-ethylhexyl) phthalate (DEHP), a common plasticizer and a suspected endocrine disruptor, exuding from polyvinyl chloride. Four species of bacteria that utilize DEHP as their sole carbon source were isolated from garden soil, one of which, strain NK0301, was markedly more efficient than the others in degrading DEHP and was chosen for further studies. Strain NK0301 was a coryneform bacterium (1.5x1.0 microm) identified as Mycobacterium sp. from its 16S rDNA sequencing homology. It readily degraded DEHP to two major products determined by gas chromatography/mass spectrometry to be 2-ethylhexanol and 1,2-benzenedicarboxylic acid. Other phthalate esters, suspected of being endocrine disruptors, were also tested and all except two could be utilized by strain NK0301 as their sole source of carbon. When strain NK0301 was cultivated on polyvinyl chloride sheets containing DEHP as the plasticizer, it removed up to 90% of DEHP in 3 d. Following this treatment, the polyvinyl chloride sheets did not exude DEHP to artificial saliva.

Improving the effectiveness of autoantibody testing in the clinic.

To enable clinicians to use autoantibody tests sensibly and economically, laboratories providing the test service have a responsibility to supply the test 'specifications'. This should include information about the test's validity and reliability, its normal range or range within a control population, its sensitivity and its specificity for different conditions against both control subjects and those with disorders which need to be distinguished by the test. This information will permit the development of predictive values, or better, of likelihood ratios which can then be used to generate clinically useful post-test probabilities. To date, autoantibody tests have been used to advantage by those skilled in their interpretation but often poorly by those less familiar with the area. It is appropriate now to demystify these tests by underpinning their clinical use with good operational data.

An origin for arsenobetaine involving bacterial formation of an arsenic-carbon bond.

Lysed-cell extract of a Pseudomonas sp. was shown to catalyse bioconversion of dimethylarsinoylacetate to arsenobetaine and dimethylarsinate. Provision of the universal methyl donor S-adenosylmethionine to bioconversion mixtures promoted both the rate and extent of arsenobetaine formation. These findings suggest that in the proposed biosynthesis of arsenobetaine from dimethylarsinoylethanol, oxidation (i.e. the formation of the carboxymethyl group of dimethylarsinoylacetate) would precede the reduction and methylation at the arsenic atom. The presence of enzyme(s) capable of methylating dimethylarsinoylacetate in a bacterial isolate from marine mussel (Mylitus edulis), highlights a possible direct involvement of prokaryotic organisms in the biosynthesis of organoarsenic compounds within marine animals.

Glycosylation of bisphenol A by tobacco BY-2 cells.

Tobacco BY-2 cells in suspension culture absorbed and transformed bisphenol A dissolved in the culture medium. Major products were bisphenol A mono-O-beta D-gentiobioside and the trisaccharide bisphenol A mono-O-beta-D-glucopyranosyl-(1-->4)-[beta-D-glucopyranosyl-(1 --> 6)] beta-D-glucopyranoside. Also produced were the mono- and di- O-beta-D-glucopyranosides. As glycosides of bisphenol A lack the estrogenic activity of the parent compound, these findings enhance the possibilities of phytoremediation of natural waters contaminated by bisphenol A. .

Interpretation of digital radiographs by pediatric critical care physicians using Web-based bedside personal computers versus diagnostic workstations.

OBJECTIVE: To determine whether the interpretations of digital radiographs by pediatric critical care physicians displayed on the bedside personal computer differ from the interpretations of images displayed on the diagnostic workstation. DESIGN: Paired comparison. SETTING: A 38-bed pediatric critical care unit in a 372-bed pediatric university hospital. SUBJECTS: Four pediatric critical care fellows and four pediatric critical care staff physicians. INTERVENTIONS: Eight critical care physicians interpreted 114 radiographs in random order on two separate occasions. Each radiograph was assessed for the presence or absence of five chest abnormalities, the correct or incorrect endotracheal tube position, and the position of central venous catheters. These interpretations were scored against a gold standard. MEASUREMENTS AND MAIN RESULTS: Sensitivity and specificity were calculated for the presence or absence of five chest abnormalities and the identification of correct or incorrect endotracheal tube position. Kappa was calculated to assess agreement in the interpretation of central catheter position. Regarding chest abnormalities, improvement in sensitivity on the diagnostic workstation was statistically significant for one critical care fellow. The specificity on the diagnostic workstation was significantly worse for two critical care fellows and two critical care staff physicians. Regarding endotracheal tube position, improvement in sensitivity on the diagnostic workstation was statistically significant for one critical care staff physician. There were no statistically significant differences between the two viewing modalities for specificity measures. For central venous catheter position, there were no statistically significant differences in the interobserver or intra-observer agreements between the two viewing modalities. CONCLUSIONS: With the exception of diffuse chest abnormalities, pediatric critical care physicians can use the Web-based bedside personal computer for clinical decision-making with the confidence that the decisions will be similar to those made on the diagnostic workstation.

Impurities in industrial grade 4,4'-isopropylidene diphenol (bisphenol A): possible implications for estrogenic activity.

Fifteen trace impurities, including a novel cyclohexene derivative, have been identified and quantified in samples of an industrial grade of the oestrogen-active compound 4,4'-isopropylidene diphenol (bisphenol A). All of these compounds, like bisphenol A itself, possess phenolic hydroxyl groups para to other substituents and all thus might also have oestrogenic properties. Published studies on the endocrine disrupting properties of bisphenol A have not considered potentially active impurities but full assessment of the oestrogenicity of bisphenol A, as it is used commercially, will become possible when adequate supplies of these compounds are available through synthesis.

Synthesis and estrogenic activity of bisphenol a mono- and di-beta-D-glucopyranosides, plant metabolites of bisphenol A.

The syntheses and characterization of bisphenol A mono- and di-beta-D-glucopyranosides were undertaken to confirm that these compounds are major plant metabolities of bisphenol A (BPA) and to allow an assessment of their estrogenicity. Synthesis involved the glucosidation of unprotected BPA with glucose penta-acetate with phosphorus oxychloride as catalyst. The estrogenic activity of BPA and its mono- and di-beta-D-glucopyranosides were measured with an enzyme-linked immunosorbent assay (ELISA)-based estrogen receptor competitive binding assay and with a yeast two-hybrid assay adapted to a chemiluminescent reporter gene (for beta-galactosidase). Both methods showed that the estrogenicity of BPA was eliminated by formation of the di-glucoside, but whereas the ELISA-based method indicated that reduced activity remained in the monoglucoside, the yeast two-hybrid method showed the monoglucoside to be inactive. Presumably these results reflect the more complex interactions of test compound and cellular components required to demonstrate estrogenicity in the yeast two-hybrid assay. As these processes parallel those in mammalian cells, the yeast two-hybrid method is likely to be the more realistic assay. The uptake and metabolism of BPA by plants offers the possibility of phytoremediation of contaminated water, but also provides an additional route for the compound to enter the human food chain.

Arsenolipids in oil from blue whiting Micromesistius poutassou--evidence for arsenic-containing esters.

Arsenic-containing lipids in the oil from the blue whiting fish (Micromesistius poutassou) were separated into three broad polarity groups and investigated by HPLC and mass spectrometry. A total of 11 arsenolipids including 4 new compounds were identified. The polar lipid fraction constituting 24% of the total arsenolipid content (which totalled 2.16 µg As/g) contained four known dimethylarsinoyl fatty acids and three known dimethylarsinoyl hydrocarbons. The less polar fraction (ca 30% of the total arsenolipids) contained four new dimethylarsinoyl hydrocarbons with chain lengths 22-30 carbons, in addition to more complex arsenicals that hydrolysed to known dimethylarsinoyl fatty acids suggesting they were conjugated carboxylic acids, presumably esters. The rest of the lipid-soluble arsenic (ca 45% of the total) remained in the non-polar fraction together with the bulk of the fish oil lipids, a complex mixture of compounds that precluded identification of the small amounts of arsenolipids.