UK audit of glomerular filtration rate measurement in 2001.

OBJECTIVE: To investigate the consistency of glomerular filtration rate (GFR) calculation from plasma sampling in the UK. METHODS: Ten patients' data sets from plasma sampling measurements of GFR were distributed throughout the UK. The data included count rates from four samples taken between 2 and 4 h after injection, a diluted sample of injected dose for standardisation, the patient's height, weight, age and sex. Participants were asked to use the routine method to calculate GFR and express the results in absolute terms (i.e. in millilitres/minute) and normalized for body surface area (ml/min/1.73 m2). Supplementary data were also requested relating to workload, method used and normal range. Intercentre variability was assessed by calculating the root median square (RMedS) deviation of each GFR from the median for that data set. Centres using a particular analysis method were grouped together and the RMedS deviation of each result from the median for that group and that data set was calculated. The influence of using normalized data and number of samples was also studied. RESULTS: Seventy-nine returns were received. For the normalized data, the overall RMedS variability was 5.8 ml/min/1.73 m2. This decreased significantly to 0.6 ml/min/1.73 m2 when results were grouped by analysis method. Results were similar for non-normalized data. A small but significant decrease in error with the number of samples was observed. CONCLUSION: Considerable variability in GFR values obtained at different centres in the UK for a given set of data was observed. Nearly all this variability was due to different methods of analysis. If methodology were standardized then intercentre variability in GFR analysis could be reduced dramatically. Radionuclide techniques are confirmed as being the method of choice if an accurate value of GFR is required.

UK audit of relative lung function measurement from planar radionuclide imaging.

BACKGROUND: Quantitative measurements of regional lung ventilation and perfusion are useful adjuncts to image interpretation. AIM: This study investigated the accuracy and precision of the software used to carry out such measurements in the UK. METHODS: Ten examples of perfusion distribution, representing the range of patterns expected in practice, were simulated on computer using a segmental model of the lung and real three-dimensional lung shapes obtained from magnetic resonance images. Pairs of anterior and posterior perfusion images were simulated and distributed to UK hospitals wishing to take part in the audit. Each centre returned analysis results and technical details. Forty centres provided data on the relative right:left lung perfusion. Thirteen also submitted data with each lung divided into three zones and four with each lung divided into two zones. All measurements were expressed by the percentage of total perfusion in a particular region. Errors were assessed as the root-mean-square (rms) deviation from the true value. RESULTS: Methods varied in the view used for analysis (80% geometric mean, 20% posterior) and the use of background subtraction (71% not used, 29% used). The rms error for percentage right assessment was 1.5 percentage points. This increased on two- and three-zone analysis to 3.8 and 4.3 percentage points, respectively. Differences in technique made little difference to whole-lung relative perfusion errors, but were important in zonal analysis. CONCLUSIONS: Quantification of whole-lung relative function is accurate and reproducible. Zonal values are determined less accurately, but still provide a useful guide to the distribution of function.

Development of potent, orally active 1-substituted-3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors.

A series of substituted 3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors, which have potential as antidiabetic agents, is described. Initial members of the series showed good enzyme inhibitory potency but poor physical properties. Optimisation of the 1-substituent led to 2,3-dihydroxypropyl compounds which showed good in vitro potency and improved physical properties, together with good DMPK profiles and acute in vivo efficacy in a rat model. X-ray crystallographic data are presented, showing an unexpected variety of binding orientations at the dimer interface site.