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Biomedical subjects

A M Peters

Publications and source records attributed to A M Peters.

At least 253 records · Page 14Linked to original sources
PubMed1984

The comparative blood clearance kinetics of modified radiolabelled erythrocytes.

The rate of clearance from blood of 111In-labelled heat damaged autologous erythrocytes (HD-RBC) has been compared with that of simultaneously injected autologous 99mTc-labelled erythrocytes (IgG-RBC) coated with a Rhesus anti-D antibody. In 17 studies, the number of antibody molecules coating the erythrocytes was 9000 (high coating) and in nine studies the number was 5000 (low coating). On gamma camera imaging, IgG-RBC uptake, at both levels of coating, could be visualized only in the spleen. HD-RBC were predominantly taken up by the spleen, although slight 111In activity was visible in the liver. The blood clearance of IgG-RBC was monoexponential, whereas that of HD-RBC was biexponential. The reciprocal of the t1/2 (the time taken for the 3 min value to fall by 50%) of the HD-RBC clearance correlated rather poorly with the rate constant of the simultaneous IgG-RBC clearance (r = 0.47, P greater than 0.05 at high coating; r = 0.75, P less than 0.05 at low coating). The rate constant of the second exponential of the HD-RBC clearance showed a correlation with the rate constant of IgG-RBC clearance that was closer than the reciprocal of the t1/2 of HD-RBC clearance (r = 0.89, P less than 0.001 at high coating; r = 0.76, P less than 0.05 at low coating) but significantly closer only at high coating. Splenic blood flow, measured using indium labelled platelets in ten subjects, correlated closely with the initial slope of HD-RBC clearance (r = 0.93, P less than 0.001).

Erythrocytes↗
PubMed1984

A simple quantitative estimate of the function of radiolabelled platelets.

The function ex vivo of autologous platelets, labelled with 111In, was evaluated at various times following injection by comparing the retention on foreign surfaces of radioactivity with the retention of total platelets (represented almost entirely by unlabelled and therefore unmanipulated platelets) after the application of fresh un-anticoagulated whole blood to (a) filter paper and (b) glass bead columns. Relative retentions were similar for the two materials, with labelled platelet retention being about 80% that of native platelet retention. Prior to injection, when labelled platelets were returned to an excess of freshly drawn whole blood, retention of radioactivity was greater than that of native platelets with a ratio significantly greater than that seen with labelled platelets tested ex vivo. Filter paper retention provides a simple technique which may be useful for the evaluation of labelled platelet function as a function of platelet age and also, with further standardisation, as an inexpensive rapid test of unlabelled platelet function.

Blood Platelets↗
PubMed1984

The interpretation of platelet kinetic studies for the identification of sites of abnormal platelet destruction.

The kinetics of platelets labelled with 111In have been studied in a series of 175 subjects including 18 normal volunteers, and 12 patients with idiopathic thrombocytopenic purpura (ITP), but excluding patients in whom there was scintigraphic evidence of intravascular platelet consumption. From analysis of the kinetics, the following parameters were calculated: splenic blood flow (SBF), intrasplenic platelet transit time (t-), splenic platelet pool capacity (expressed as a percentage of the total circulating platelet population), the fraction of the dose of labelled platelets ultimately destroyed in the spleen and the mean platelet life span (MPLS). SBF increased with increasing spleen size up to values of 25% total blood volume (TBV) per min. Some patients with immune complex related diseases were identified with elevated SBF (up to 24% TBV min-1) but without significant splenomegaly. Patients with cardiac decompensation had reduced SBF relative to spleen size. t- showed no relationship with spleen size. It tended to fall in patients who had high SBF relative to spleen size and to rise in those with low SBF relative to spleen size; i.e. it was inversely related to splenic perfusion (flow per unit tissue volume). The splenic platelet pool capacity is dependent on platelet input (SBF) and splenic platelet clearance (reciprocal of t-), and showed a close relationship with spleen size. When all subjects except those with ITP were considered, splenic platelet destruction showed a good correlation (r = 0.70, n = 42, P less than 0.001) with the splenic platelet pooling capacity. The ratio of the fraction of platelets destroyed in the spleen to the fraction pooling there, the D/P ratio, was approximately unity and did not appear to vary with MPLS, spleen size or the patient's condition, except in ITP where it varied between about 0.5 and 2. This variation in ITP was thought to be the result of an immune mediated re-direction of reticulo-endothelial platelet destruction. It is suggested that the D/P ratio, rather than the absolute quantity of 111In labelled platelets destroyed in the spleen, may be a more useful predictor of response to splenectomy since it takes into account the observed, appropriate, tendency for the spleen to destroy platelets in proportion to its platelet pooling capacity.

Blood Flow Velocity↗
PubMed1984

Methods of measuring splenic blood flow and platelet transit time with In-111-labeled platelets.

Following bolus intravenous injection of In-111-labeled autologous platelets in humans, splenic blood flow (SBF) was measured by compartmental analysis of the equilibration of platelets between blood and the intrasplenic platelet pool. The result correlated closely (r = 0.94, p less than 0.001) with SBF measured from analysis of the first-pass time-activity curve recorded over the spleen by external detection. The intrasplenic platelet transit time (tp), measured concurrently with SBF from compartmental analysis, correlated closely (r = 0.78, p less than 0.001) with tp measured from deconvolution analysis. These correlations appear to support the use of compartmental analysis of the equilibration of radiolabeled platelets between blood and the intrasplenic platelet pool as a valid technique for the simultaneous measurement of SBF and tp. Both of these parameters have potential clinical usefulness for the understanding of intrasplenic platelet kinetics in a variety of disorders.

Blood Platelets↗
PubMed1983

A study of platelet-relevant parameters in patients with diabetic microangiopathy.

In 16 diabetic patients with microangiopathy, survival of 111In-labelled autologous platelets, mean platelet volume, megathrombocyte index, spontaneous and ADP-induced platelet aggregation, platelet retention, beta-thromboglobulin, von Willebrand factor and factor VIII-related antigen were measured; the splenic uptake of radioactive label was quantitated in six patients. Compared with normal subjects, increased platelet aggregation (p less than 0.01), von Willebrand factor (p less than 0.02) and factor VIII-related antigen (p less than 0.02) were observed. Platelet survival was shortened in two patients. It correlated inversely with the splenic radioactivity uptake (r = -0.95; p less than 0.01), suggesting that platelets ended their life in the spleen, not in the microcirculation. No significant relationships were found between the various tests performed, nor between these and the severity of microangiopathy or other clinical data. In spite of the evidence for altered platelet function in patients with diabetic microangiopathy, currently available tests are not specific enough to clarify the nature of these changes or their possible pathogenic significance.

Adult↗
PubMed1983

Indium-111 tropolonate leucocyte scanning in the detection of intra-abdominal abscesses.

Indium-111 leucocyte scanning is established as an accurate method for localising intra-abdominal abscesses. With the currently available cell labelling techniques there is a variable and significant delay in localisation of abscesses which is a major disadvantage in comparison with ultrasound or computed tomography. We have examined the speed and accuracy of localisation of leucocytes labelled in plasma with a new chelating agent, indium-111 tropolonate, in 90 patients with suspected intra-abdominal abscess. In 50 patients a comparison with ultrasound was made. Nineteen patients had abscesses. The sensitivity and specificity of labelled leucocytes were 95% and 99%, respectively. Comparative results for ultrasound were 60% and 83%. In nine out of 10 patients with abscesses scanned sequentially from 40 min after return of the labelled cells, activity corresponding to the abscess was already visible on the 40 min scan. These results demonstrate that indium-111 plasma labelled leucocyte scanning is both rapid and an accurate method of detecting abscesses.

Abdomen↗
PubMed1983

Platelet kinetics with indium-111 platelets: comparison with chromium-51 platelets.

The application of 111In-oxine to platelet labeling has contributed to the understanding of platelet kinetics along three lines: 1. It allows the measurement of new parameters of splenic function, such as the intrasplenic platelet transit time, which has shed new light on the physiology of splenic blood cell handling. 2. It facilitates the measurement of platelet life span in conditions, such as ITP, in which 51Cr may undergo undesirable elution from the platelet as a result of platelet-antibody interaction. 3. It allows the determination of the fate of platelets, that is, the site of platelet destruction in conditions in which reduced platelet life span is associated with abnormal platelet consumption, as a result of either premature destruction of "abnormal" platelets by the RE system, or the consumption (or destruction) of normal platelets after their interaction with an abnormal vasculature. Future research using 111In platelets may yield further valuable information on the control as well as the significance of intrasplenic platelet pooling, on the role of platelets in the development of chronic vascular lesions, and on the sites of platelet destruction in ITP. With regard to the latter, methods will have to be developed for harvesting sufficient platelets representative of the total circulating platelet population from severely thrombocytopenic patients for autologous platelet labeling. This would avoid the use of homologous platelets, which is likely to be responsible for some of the contradictory data relating to the use of radiolabeled platelet studies for the prediction of the response of patients with ITP to splenectomy.

Blood Flow Velocity↗
PubMed1983

Measurement of splenic blood flow in the anaesthetised dog using electromagnetic flowmetry and indium labelled platelets.

Splenic blood flow has been measured in the dog using indium labelled autologous platelets (SBFp) and compared with splenic blood flow measured with an electromagnetic flowmeter placed on the splenic vein (SVBF). The overall correlation between SBFp and SVBF was only moderately close (r = 0.54, P less than 0.01) and SBFp was about half SVBF. When expressed as a change between sequential measurements in an individual animal, the correlation between SBFp and SVBF was closer (r = 0.85, P less than 0.001). It was concluded that SBFp is a specific measure of splenic pulp blood flow and that the discrepancy between SBFp and SVBF reflects the degree of splenic blood flow bypassing the pulp.

Animals↗
PubMed1983

Lung transit of 111Indium-labelled granulocytes. Relationship to labelling techniques.

The early in vivo distribution of 111Indium-labelled granulocytes, recorded by dynamic imaging using a gamma camara and computer, varied according to the separation and labelling technique. Following i.v. bolus injection, 4 kinetic patterns could be identified: (A) rapid transit through the pulmonary vasculature, (B) delayed transit through the lung with clearance by about 30 min, (C) complete retention by the lung, for up to 10 min, followed by slow release over a period of 1 to 2 h, (D) delayed transit through the lung with a similar time course to (B) but with subsequent heavy liver uptake. Granulocytes labelled with 111In-tropolonate and maintained in plasma throughout the labelling procedure, whether injected as a 'pure' (separated by plasma-enriched density gradient centrifugation) or 'crude' (separated by differential centrifugation) preparation, displayed type A kinetics, thought to most closely represent the normal behaviour of granulocytes. 'Crude' cells labelled in saline with 111In-acetylacetonate displayed type B kinetics. 'Pure' cells isolated on Percoll-saline and labelled in saline with 111In-acetylacetonate displayed type C kinetics, thought to represent granulocyte 'stimulation' and/or damage, or type D kinetics, thought to represent severe damage. The importance is stressed of labelling granulocytes for kinetic studies with a technique that results in minimal alteration of cell behaviour.

Cell Movement↗
PubMed1983

111Indium autologous leucocytes in inflammatory bowel disease.

A non-invasive method of imaging and assessing inflammatory bowel disease is described. 111Indium labelled leucocyte scans were performed on 33 patients with a wide variety of inflammatory bowel diseases and 25 control patients. All patients with moderate or severe inflammatory bowel disease had positive scans with localisation of abnormal activity corresponding to the sites assessed to be diseased by radiology in either small or large bowel. No false positives were recorded in the control patients. Faecal excretion of 111In labelled leucocytes was increased in patients with inflammatory bowel disease according to disease severity and correlated with disease activity assessed by serum C-reactive protein levels (r = 0.74, p less than 0.001) or in those patients with Crohn's disease by Crohn's Disease Activity Index (r = 0.78, p less than 0.001). These data suggest that 111In labelled leucocytes may be used to provide a safe, non-invasive method of imaging diseased bowel and objectively assessing disease activity.

Colitis, Ulcerative↗
PubMed1983

Assessment of disease activity in ulcerative colitis using indium-111-labelled leukocyte faecal excretion.

A new method of assessing disease activity in ulcerative colitis has been developed utilizing indium-111-labelled granulocytes. Faecal 111In excretion after intravenous administration of labelled granulocytes ranged from 1.1% to 45% of the injected dose in patients with ulcerative colitis, showing significant differences between mild, moderate, and severely active groups. There was a significant correlation between faecal 111In excretion and a clinical index based on the Crohn's disease activity index (r = 0.79, p less than 0.001) and the erythrocyte sedimentation rate (r = 0.73, p less than 0.001). Quantitative faecal 111In-labelled granulocyte excretion is an objective and specific method of assessing disease activity in ulcerative colitis.

Adolescent↗
PubMed1983

Quantitative fecal indium 111-labeled leukocyte excretion in the assessment of disease in Crohn's disease.

The assessment of disease activity in Crohn's disease involves determination of either clinical indexes (e.g., Crohn's disease activity index) or laboratory measurements (e.g., C-reactive protein and erythrocyte sedimentation rate). These have the disadvantage of being indirect and nonspecific correlates of gut inflammation. We have assessed disease activity in Crohn's disease by measurement of fecal leukocyte excretion after intravenous administration of either 111In-labeled mixed leukocyte or pure granulocyte preparations. With mixed leukocyte preparations, fecal excretion of radioactivity correlated with Crohn's disease activity index (r = 0.78, p less than 0.001) and C-reactive protein (r = 0.74, p less than 0.01). Using pure granulocytes, fecal 111In excretion (range 1.5%-52%) was much higher than with mixed leukocytes (range 0.1%-11.0%), showing significant correlations with Crohn's disease activity index (r = 0.731, p less than 0.001), C-reactive protein (r = 0.716, p less than 0.001), and erythrocyte sedimentation rate (r = 0.676, p less than 0.001). Quantitative fecal excretion of 111In-leukocytes is a new method of assessing disease activity in Crohn's disease, specific for bowel inflammation and suitable for objective assessment of disease activity in therapeutic trials.

Blood Sedimentation↗
PubMed1983

Imaging of inflammation with indium-111 tropolonate labeled leukocytes.

Indium-111 tropolonate has recently been introduced as a new cell-labeling agent. It has the interesting property of labeling cells in plasma with high efficiency, and may therefore promote an improvement in viability of labeled cells. This paper describes our initial experience with In-111 tropolonate as a leukocyte label for abscess imaging. Pure populations of separated granulocytes, as well as crude leukocyte preparations, have been labeled. Of 101 studies performed, 51 were positive (no false positives) and 50 negatives, of which only two were false negatives. Localization in sites of inflammation was prominent and rapid. Of 36 positive studies, 27 were already positive at 40 min following injection and an additional nine at 3 hr. Of the other 15 positive studies, 11 were scanned for the first time at 3 hr, when they were positive. Granulocytes labeled with this agent in plasma showed minimal sequestration in lungs and liver, interpreted as indicating improved viability in comparison with cells displaying prolonged lung sequestration.

Abdomen↗
PubMed1983

Measurement of granulocyte migration and accumulation in inflammation in man.

A method has been developed for studying granulocyte kinetics in inflammation. Autologous granulocytes isolated from whole blood and labelled with 111indium, without separation from plasma enriched media, localized rapidly in intra-abdominal abscesses and inflammatory bowel disease following intravenous reinjection. Utilizing a gamma camera interfaced to a computer for dynamic imaging, uptake of activity in the site of inflammation could be demonstrated from 10 min following injection. A quantitative estimate of the rate of granulocyte uptake in inflammatory foci, (early granulocyte accumulation index EGAI) was made by subtracting the gradient of the time activity profile, recorded over the inflammatory focus from that of the profile recorded over a similar sized control region, and expressing the difference in relation to the zero time intercept of the profile over the inflammatory focus. The EGAI showed a positive correlation with the ESR (sigma = 0.574; P less than 0.05) and, in the single patient studied twice, decreased following steroid therapy. This technique should prove useful in studying granulocyte kinetics in inflammation in man.

Abdomen↗
PubMed1982

Evaluation of heat-damaged and IgG-coated red cells for testing reticuloendothelial function.

In vitro methods for standardising and assessing the reproducibility of reticuloendothelial function tests in man were performed. Variation in the degree of heat-induced red blood cell damage could be detected by both Channelyzer plots and a filtration test of red cell plasticity although the former test was less sensitive and difficult to quantitate. In a consecutive study of the clearance of heat-damaged red blood cells (HDRBC) in 8 patients and 2 normal individuals, consistent changes were demonstrated by both assays although occasionally one assay alone provided inconclusive results. When undamaged red cells were coated with IgG anti-D antibodies, the number of IgG molecules bound per red cell was determined by an indirect antiglobulin radioimmunoassay. With this assay, it was shown that the rate of clearance of coated cells was related to the amount of cell bound IgG anti-D. Some variation in the degree of coating of cells from patients with systemic lupus erythematosus was found although the differences were insufficient to account for the reported reduction in the clearance of IgG-coated cells in patients with this disease. The radioimmunoassay and microhaemagglutination techniques revealed that neither IgG, Clq, C3 or C3d were bound to HDRBC following incubation in autologous serum suggesting that these cells were cleared in vivo by mechanisms unrelated to immune receptor recognition.

Antibodies, Anti-Idiotypic↗