Subtle changes in individual joints result in both positive and negative change scores in a patient: results from a clinical trial in patients with rheumatoid arthritis

Radiographic progression in clinical trials is assessed by interpreting changes in total radiographic joint score, and the reliability of those scores depends on an evaluation of sum scores. It is not known how consistently changes in individual joints are identified by independent readers and in independent readings. Patients and 7255 single joints from 178 patients who participated in the Trial of Etanercept and Methothrexate with Radiographic Patient Outcomes (TEMPO) trial were evaluated. Every image was independently scored twice according to the Sharp-van der Heijde method by two independent readers, so that four scores per joint were available. Absolute agreement and consistency of negative and positive erosion change scores across readers and readings were compared on a per-joint level, as well as on a per-patient level. The number of joints showing a change for erosion was very low in this trial: 691/7255 analysed joints had at least one non-zero change score out of four readings. Absolute agreement between readings was remarkably poor: only 12 joints showed a consistently positive or negative change in all four readings. Change scores in opposite directions in the same joint across independent readings were rare (25 joints). Frequency of opposite joint scores in the same patient (mixed change patterns) was reader dependent. Substantial intra and interreader disagreement in scoring change in individual joints is common. Opposite joint scores in the same patient, however, are rare and reader dependent. Notwithstanding these subtle inconsistencies on the individual joint level, the total Sharp score is a useful and discriminatory outcome measur

Pulmonary hypertension after transjugular intrahepatic portosystemic shunt (TIPS)

We reported the case of a patient in whom severe, and ultimately fatal, pulmonary hypertension developed 1.5 yrs after transjugular intrahepatic portosystemic shunt (TIPS). Pulmonary artery pressures were not affected by 100% oxygen, prostacyclin or nifedipine. Postmortem examinations showed pulmonary and vascular abnormalities typical of pulmonary hypertension. Pulmonary artery pressures should be measured in each patient with otherwise not readily explained dyspnoea following transjugular intrahepatic portosystemic shunt

Pulmonary granulocyte influx and impaired alveolar macrophage adenylyl cyclase responsiveness in developing respiratory distress

Alveolar macrophages have recently been postulated as being involved in the aetiology of adult respiratory distress syndrome (ARDS). To evaluate their role, basal cyclic AMP levels and responsiveness of adenylyl cyclase alveolar macrophages were determined at four intermediate stages of developing respiratory distress in piglets using a protocol with repeated lung lavage. Examination of alveolar cells recovered from the subsequent lavages reveals an influx of granulocytes (neutrophils and eosinophils) within 1 h of two intensive lung lavages. During the developing respiratory distress the basal cyclic AMPlevel of alveolar macrophages increases and adenylyl cyclase responsiveness to prostaglandin E2 (PGE2) and isoprelanaline diminishes. The previously observed impairment of macrophage activity can then be explained at a subcellular level

Predictors of response to anti-TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register

Objective. Few data exist on the use of anti-TNF drugs for AS during routine clinical use in the UK. This report describes an improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) after 6 months of therapy in 261 patients enrolled in a national prospective observational register

Effects of infliximab on markers of inflammation and bone turnover and associations with bone mineral density in patients with ankylosing spondylitis

Using a micro-extruder a new class of polyurethanes, polyacylurethanes (PAUs), based on poly (epsilon-caprol actone) (PCL) oligomers and terephthaloyl diisocyanate was synthesized. These polymers are anticipated to have potential for biodegradable and/or biomedical applications. Therefore, PAUs were synthesized without the use of any, possibly toxic, catalysts. PCL diols of different molecular mass were used, namely 750, 1000, 1250, 1500, 2000, 3000 and 4000 g/mol. These diols were synthesized by thermal polymerization at 150 degrees C without the use of any catalyst. The PAUs of terephthaloyl diisocyanate were synthesized by reactive extrusion using a micro-extruder of 5 cm 3 at 130 degrees C. The PAUs obtained were characterized using DSC, GPC, DMTA, SAXS and tensile testing. Surprisingly, PAUs based on PCL chains of 750, 1000, 1250 and 1500 g/mol were found to show microphase separation/micro crystallization as proven by SAXS data combined with DSC. This microphase separation creates elastomeric properties as is known from polyurethanes. In the PAUs based on PCL chains of 2000, 3000 and 4000 g/mol part of the PCL was found to crystallize and no evidence of any phase separation of the acylurethane block was found. (c) 2005 Elsevier Ltd. All rights reserved