Construction and characterization of a single-chain catalytic antibody.

The antigen-binding (Fab) fragment of the catalytic monoclonal antibody NPN43C9 has recently been cloned by using bacteriophage lambda. By inserting the variable regions of this Fab coding sequence into a (NH2)-VL-linker-VH-(COOH) construct (where VL and VH represent the heavy and light chain variable regions), we have assembled a recombinant gene encoding a catalytic single-chain antigen-binding protein. This protein has been expressed in Escherichia coli and exhibits the same catalytic parameters as the parent monoclonal antibody NPN43C9. Single-chain forms of catalytic antibodies may prove valuable for structural and site-directed mutagenesis studies as well as for large-scale applications of catalytic antibodies.     

Cost of illness of inflammatory bowel disease in the UK: a single centre retrospective study

BACKGROUND AND AIMS: The potentially high costs of care associated with inflammatory bowel disease (IBD) are recognised but we have little knowledge of the scale, profile, or determinants of these costs in the UK. This study aimed to describe costs of illness for a group of IBD patients and determine factors associated with increased healthcare costs. SETTING: A university hospital serving a target population of approximately 330 000. PATIENTS AND METHODS: A six month cohort of IBD patients receiving any form of secondary care was identified, comprising 307 cases of ulcerative (or indeterminate) colitis and 172 cases of Crohn's disease. Demographic and clinical data were abstracted from clinical records and individual resource use was itemised for all attributable costs (including extraintestinal manifestations). Item costs were derived from national and local sources. Cost data were expressed as mean six month costs per patient (with 95% confidence interval (CI)) obtained using non-parametric bootstrapping. Determinants of cost were analysed using generalised linear regression modelling. A postal survey of patients was undertaken to examine indirect costs, out of pocket expenses, and primary care visits. RESULTS: Inpatient services (medical and/or surgical) were required by 67 patients (14%) but accounted for 49% of total secondary care costs. Drug costs accounted for less than a quarter of total costs. Individual patient costs ranged from 73 to 33,254 UK pounds per six months. Mean (95% CI) six month costs per patient were 1256 UK pounds ( 988 pounds, 1721 pounds) for colitis and 1652 UK pounds (1221 pounds, 2239 pounds) for Crohn's disease. Hospitalisation, disease severity grade, and disease extent correlated positively with cost of illness but costs were independent of age or sex. Compared with quiescent cases of IBD, disease relapse was associated with a 2-3-fold increase in costs for non-hospitalised cases and a 20-fold increase in costs for hospitalised cases. Survey data suggested average six month costs were < 30 UK pounds per patient for primary care visits (both diseases) and median loss of earnings were 239 UK pounds for colitis and 299 UK pounds for Crohn's disease. CONCLUSIONS: This study represents the first detailed characterisation of the scale and determinants of costs of illness for IBD in a British hospital. Hospitalisation affected a minority of sufferers but accounted for half of the total direct costs falling on the healthcare system.     

Evaluation of delivery of enhanced diabetes care to patients of South Asian ethnicity: the United Kingdom Asian Diabetes Study (UKADS).

AIMS: We tested the hypothesis that enhanced care for diabetes, tailored to the needs of the South Asian community with Type 2 diabetes, would improve risk factors for diabetic vascular complications and ultimately reduce morbidity and mortality. PATIENTS AND METHODS: The study was a cluster randomized controlled trial (RCT) with general practice the unit of randomization. Six West Midlands general practices with a high proportion of South Asian patients were randomized to 'enhanced care' using Asian link workers and extra community diabetes specialist nurse sessions (intervention) or continued standard practice care (control). RESULTS: Of 401 patients recruited to the study, 361 (90%), comprising 178 from Coventry and 183 from Birmingham were eligible and included in the analyses. The mean age at baseline (standard deviation, SD) was 58.9 (11.7 years) with median (interquartile range; IQR) duration of diabetes 6.5 (3-11) years. At one year follow-up there was a significant difference in reduction of systolic (4.6 mmHg, P = 0.035) and diastolic blood pressure (3.4 mmHg, P = 0.003) and total cholesterol (0.4 mmol/l, P = 0.005), comparing the intervention and control groups. After adjusting for baseline measurement and age, only differential reduction in diastolic blood pressure remained significant. There was no significant change in HbA(1c) and no difference between the groups. CONCLUSIONS: Using link workers and extra community diabetes specialist nurse input together with treatment protocols in primary care might prove a useful strategy in working towards NSF targets for diabetes management. In this study, small reductions in blood pressure and cholesterol were achieved. Improvement in glycaemic control may require longer and possibly different strategies. Further research is required to evaluate fully the effectiveness, including the costs and longer term sustainability of culturally sensitive initiatives.     

Preferential coronary arterial drug delivery

A transcatheter technique for administering drugs preferentially to the canine left coronary circulation is described. The method involves pulsed, diastolic, small-volume (0.2 ml) injections through a specially designed aortic cusp catheter. In order to evaluate preferential delivery to the coronary circulation, papaverine was administered using this technique and compared to intravenous delivery. Left circumflex and carotid arterial blood flow, as well as systemic arterial pressure, were simultaneously measured. In eight of ten animals studied, diastolic aortic cusp administration of the drug for periods of up to 30 minutes increased circumflex flow an average of 136%, increased carotid arterial flow 22%, and decreased systemic arterial pressure 18%. Intravenous delivery increased circumflex flow an average of 34%, increased carotid flow 41%, and decreased systemic arterial pressure 13%. The technique has immediate research and potential clinical application as a means of preferentially delivering diagnostic or therapeutic agents, such as thrombolytics, to the coronary circulation.     

Effect of Asthma Call-back Survey methodology changes on work-related asthma estimates, 19 states, 2007–2012

Objective: Asthma Call-back Survey methodology has been changed recently, as a new sampling design, weights calculation (2011–2012), and revised work-related asthma (WRA) section (2012) were implemented. To assess the effect of these changes on the WRA and possible WRA estimates among ever-employed adults with current asthma, we analyzed 2007–2012 data for 37?505 ever-employed adults (≥18 years) collected from 19 US states (representing an estimated 10 million adults each year). Methods: Using data from landline telephone (LLP) households, we calculated estimates applying poststratification weights (2007–2010) and “raking” weights (2011–2012). Also, using data from LLP/cellular telephone (CP) households combined, we calculated estimates applying “raking” weights (2012). Results: Based on LLP household data, the WRA estimates ranged from 7.8% to 9.7% during 2007–2010, was 9.1% in 2011 and 15.4% in 2012. Possible WRA estimates ranged from 35.1% to 38.1% during 2007–2010, was 38.1% in 2011 and 39.8% in 2012. Using the 2012 LLP/CP household data, the WRA and possible WRA estimates were 15.4% and 38.9%, respectively. Conclusions: Implementation of “raking” weights did not substantially change the WRA or possible WRA estimates among ever-employed adults with current asthma. The WRA and possible WRA estimates based on LLP and LLP/CP samples in 2012 were comparable, as CP users are younger and less likely to have WRA. The substantial upward shift in the 2012 WRA estimates likely was associated with the revision to the WRA section.     

Rapid Increase in Marrow Fat Content and Decrease in Marrow Perfusion in Lumbar Vertebra Following Bilateral Oophorectomy: An MR Imaging-Based Prospective Longitudinal Study

ObjectiveBilateral oophorectomy leads to reduced bone mineral density (BMD), and reduced BMD is associated with increased marrow fat and reduced marrow perfusion. Purpose of this study was to investigate how soon these changes occur following surgical oophorectomy.ResultsReduced BMD, increased marrow FF, and reduced marrow perfusion occurred synchronously post-oophorectomy. There was a sharp decrease of 12.5 ± 7.2% in BMD (n = 6), a sharp increase of 92.2 ± 46.3% (n = 6) in FF, a sharp decrease of 23.6 ± 3.9% in maximum contrast enhancement (n = 5), and of 45.4 ± 7.7% for enhancement slope (n = 5) during the initial 3 months post surgery. BMD and marrow perfusion continued to decrease, and marrow FF continued to increase at a slower rate during the following 18 months. Friedman test showed a significant trend for these changes (p < 0.05).ConclusionBilateral oophorectomy leads to a rapid decrease in lumbar BMD, an increase in marrow fat content, and a decrease in marrow blood perfusion.     

Legg‐Calvé‐Perthes Disease Produces Chronic Hip Synovitis and Elevation of Interleukin‐6 in the Synovial Fluid

Legg‐Calvé‐Perthes disease (LCPD) is a childhood hip disorder of ischemic osteonecrosis of the femoral head. Hip joint synovitis is a common feature of LCPD, but the nature and pathophysiology of the synovitis remain unknown. The purpose of this study was to determine the chronicity of the synovitis and the inflammatory cytokines present in the synovial fluid at an active stage of LCPD. Serial MRI was performed on 28 patients. T2‐weighted and gadolinium‐enhanced MR images were used to assess synovial effusion and synovial enhancement (hyperemia) over time. A multiple‐cytokine assay was used to determine the levels of 27 inflammatory cytokines and related factors present in the synovial fluid from 13 patients. MRI analysis showed fold increases of 5.0 ± 3.3 and 3.1 ± 2.1 in the synovial fluid volume in the affected hip compared to the unaffected hip at the initial and the last follow‐up MRI, respectively. The mean duration between the initial and the last MRI was 17.7 ± 8.3 months. The volume of enhanced synovium on the contrast MRI was increased 16.5 ± 8.5 fold and 6.3 ± 5.6 fold in the affected hip compared to the unaffected hip at the initial MRI and the last follow‐up MRI, respectively. In the synovial fluid of the affected hips, IL‐6 protein levels were significantly increased (LCPD: 509 ± 519 pg/mL, non‐LCPD: 19 ± 22 pg/mL; p = 0.0005) on the multi‐cytokine assay. Interestingly, IL‐1β and TNF‐α levels were not elevated. In the active stage of LCPD, chronic hip synovitis and significant elevation of IL‐6 are produced in the synovial fluid. Further studies are warranted to investigate the role of IL‐6 on the pathophysiology of synovitis in LCPD and how it affects bone healing. © 2015 American Society for Bone and Mineral Research