Ravin Sobnack

Autologous 111In-labelled platelet sequestration studies in patients with primary immune thrombocytopenia (ITP) prior to splenectomy: a report from the United Kingdom ITP Registry

While splenectomy is an effective therapy for primary immune thrombocytopenia (ITP), possible complications and observed non‐complete response (CR) in one‐third of patients demonstrate the need for further research into potential pre‐surgical predictors of outcomes. Past investigations into platelet sequestration studies, a hypothesized predictive test, have adopted heterogeneous methods and varied widely with regard to power. By studying patients with primary ITP who underwent autologous 111In‐labelled platelet sequestration studies at Barts and The London NHS Trust between 1994 and 2008, we evaluated the effectiveness of sequestration site in predicting short, medium, and long‐term CR (platelet count >100 × 109/l) to splenectomy through multivariate (gender, age at splenectomy, and mean platelet lifespan) logistic regression modelling. In total, 256 patients with primary ITP underwent scans; 91 (35·5%) proceeded to splenectomy. Logistic regression revealed significant adjusted odds ratios for CR of 7·47 (95% confidence interval [CI], 1·89–29·43) at 1–3 months post‐splenectomy, 4·85 (95% CI, 1·04–22·54) at 6–12 months post‐splenectomy, and 5·39 (95% CI, 1·34–21·65) at last follow‐up (median: 3·8 years [range: 0·5–13·1 years]) in patients with purely or predominantly splenic versus mixed or hepatic sequestration. These findings demonstrate the utility of autologous 111In‐labelled platelet sequestration studies as an adjunct predictive instrument prior to splenectomy.

Extracellular fluid volume and glomerular filtration rate in 1878 healthy potential renal transplant donors: effects of age, gender, obesity and scaling

UNLABELLED Aim. The aim of this study was to investigate the influence of age, gender, obesity and scaling on glomerular filtration rate (GFR) and extracellular fluid volume (ECV) in healthy subjects. METHODS This is a retrospective multi-centre study of 1878 healthy prospective kidney transplant donors (819 men) from 15 centres. Age and body mass index (BMI) were not significantly different between men and women. Slope-intercept GFR was measured (using Cr-51-EDTA in 14 centres; Tc-99m-DTPA in one) and scaled to body surface area (BSA) and lean body mass (LBM), both estimated from height and weight. GFR was also expressed as the slope rate constant, with one-compartment correction (GFR/ECV). ECV was measured as the ratio, GFR to GFR/ECV. RESULTS ECV was age independent but GFR declined with age, at a significantly faster rate in women than men. GFR/BSA was higher in men but GFR/ECV and GFR/LBM were higher in women. Young women (<30 years) had higher GFR than young men but the reverse was recorded in the elderly (>65 years). There was no difference in GFR between obese (BMI>30 kg/m2) and non-obese men. Obese women, however, had lower GFR than non-obese women and negative correlations were observed between GFR and both BMI and %fat. The decline in GFR with age was no faster in obese versus non-obese subjects. ECV/BSA was higher in men but ECV/LBM was higher in women. ECV/weight was almost gender independent, suggesting that fat-free mass in women contains more extracellular water. BSA is therefore a misleading scaling variable. CONCLUSION There are several significant differences in GFR and ECV between healthy men and women.

99Tcm-labelled leucocyte imaging in active rheumatoid arthritis

A simplified technique of labelling leucocytes with technetium-99m is described and applied to patients with active rheumatoid arthritis. The clinically active and less active knees in seven patients were imaged and the uptake of labelled leucocytes was measured. The measurements were repeated after local steroid injection into nine painful knees. A 50-80% reduction in leucocyte uptake localized to the region of the synovium was demonstrated in the eight knees which showed clinical responses and a rise of 8% in the non-responder. There was a variable response in the knees that were not injected. 99Tcm leucocyte imaging in rheumatoid arthritis is able to assess objectively joint inflammation and its response to treatment.

The reliability of glomerular filtration rate measured from plasma clearance: a multi-centre study of 1,878 healthy potential renal transplant donors

PurposeThe objective of the study was to undertake a clinical audit of departmental performance in the measurement of glomerular filtration rate (GFR) using the coefficient of variation (CV) of extracellular fluid volume (ECFV) as the benchmark. ECFV is held within narrow limits in healthy subjects, narrower than GFR, and should therefore have a low CV.MethodsFifteen departments participated in this retrospective study of healthy renal transplant donors. Data were analysed separately for men (n ranged from 28 to 115 per centre; total = 819) and women (n = 28–146; 1,059). All centres used the slope-intercept method with blood sample numbers ranging from two to five. Subjects did not fast prior to GFR measurement. GFR was scaled to body surface area (BSA) and corrected for the single compartment assumption. GFR scaled to ECFV was calculated as the terminal slope rate constant and corrected for the single compartment assumption. ECFV/BSA was calculated as the ratio of GFR/BSA to GFR/ECFV.ResultsThe departmental CVs of ECFV/BSA and GFR/BSA ranged from 8.3 to 25.8% and 12.8 to 21.9%, respectively, in men, and from 9.6 to 21.1% and 14.8 to 23.7%, respectively, in women. Both CVs correlated strongly between men and women from the same centre, suggesting department-specific systematic errors. GFR/BSA was higher in men in 14 of 15 centres, whereas GFR/ECFV was higher in women in 14 of 15 centres. Both correlated strongly between men and women, suggesting regional variation in GFR.ConclusionThe CV of ECFV/BSA in normal subjects is a useful indicator of the technical robustness with which GFR is measured and, in this study, indicated a wide variation in departmental performance.

The response of 99Tcm-methylene diphosphonate and 99Tcm-hexametazime-labelled neutrophils to intra-articular steroid injection in rheumatoid arthritis

The synovial and bone uptake of tracer in the knees of patients with rheumatoid arthritis (RA) was quantified using 99Tcm-hexamethyl propylene amine oxime-labelled leucocytes and 99Tcm-methylene diphosphonate (MDP), respectively. Significant neutrophil migration and MDP uptake occurred in the knees of patients with RA irrespective of the disease duration. In all but one patient neutrophil migration was reduced after intra-articular steroid injection. The change in MDP uptake after steroid injection was variable. There was a significant correlation between the percentage reduction in neutrophil migration and pain score, while the latter correlated poorly with the change in MDP uptake. The quantification of the neutrophil component of the inflammatory process is a sensitive index for monitoring RA activity and response to pharmacological interventions, while quantitative bone scintigraphy should not be employed to monitor changes in joint inflammation in patients with RA.

Higher extracellular fluid volume in women is concealed by scaling to body surface area

Abstract Objective. The objective was to assess body surface area (BSA) for scaling extracellular fluid volume (ECV) in comparison with estimated lean body mass (LBM) and total body water (TBW) across a range of body mass indices (BMI). Methods. This was a multi-centre study from 15 centres that submitted raw data from routine measurement of GFR in potential kidney transplant donors. There were 819 men and 1059 women in total. ECV was calculated from slope-intercept and slope-only measurements of GFR. ECV was scaled using two methods: Firstly, division of ECV by the scaling variable (ratio method), and secondly the regression method of Turner and Reilly. Subjects were placed into five BMI groups: < 20, 20–24.9, 25–29.9, 30–34.9, and 35 + kg/m2. LBM and TBW were estimated from previously published, gender-specific prediction equations. Results. Ratio and regression scaling gave almost identical results. ECV scaled to BSA by either method was higher in men in all BMI groups but ECV scaled to LBM and TBW was higher in women. There was, however, little difference between men and women in respect to ECV per unit weight in any BMI group, even though women have 10% more adipose tissue. The relations between TBW and BSA and between LBM and BSA, but not between LBM and TBW, were different between men and women. Conclusion. Lean tissue in women contains more extracellular water than in men, a difference that is obscured by scaling to BSA. The likely problem with BSA is its insensitivity to body composition.

Autologous 111In-labelled platelet sequestration studies in patients with primary immune thrombocytopenia (ITP) prior to splenectomy: a report from the United Kingdom ITP Registry: 111Indium Studies Prior to Splenectomy for ITP

While splenectomy is an effective therapy for primary immune thrombocytopenia (ITP), possible complications and observed non‐complete response (CR) in one‐third of patients demonstrate the need for further research into potential pre‐surgical predictors of outcomes. Past investigations into platelet sequestration studies, a hypothesized predictive test, have adopted heterogeneous methods and varied widely with regard to power. By studying patients with primary ITP who underwent autologous 111In‐labelled platelet sequestration studies at Barts and The London NHS Trust between 1994 and 2008, we evaluated the effectiveness of sequestration site in predicting short, medium, and long‐term CR (platelet count >100 × 109/l) to splenectomy through multivariate (gender, age at splenectomy, and mean platelet lifespan) logistic regression modelling. In total, 256 patients with primary ITP underwent scans; 91 (35·5%) proceeded to splenectomy. Logistic regression revealed significant adjusted odds ratios for CR of 7·47 (95% confidence interval [CI], 1·89–29·43) at 1–3 months post‐splenectomy, 4·85 (95% CI, 1·04–22·54) at 6–12 months post‐splenectomy, and 5·39 (95% CI, 1·34–21·65) at last follow‐up (median: 3·8 years [range: 0·5–13·1 years]) in patients with purely or predominantly splenic versus mixed or hepatic sequestration. These findings demonstrate the utility of autologous 111In‐labelled platelet sequestration studies as an adjunct predictive instrument prior to splenectomy.