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Biomedical subjects

A M Peters

Publications and source records attributed to A M Peters.

At least 217 records · Page 12Linked to original sources
PubMed1988

In vitro studies with an anti-platelet monoclonal antibody; P256.

P256 is a platelet-specific monoclonal antibody. It has potential as a diagnostic agent for use in thrombus detection by radioimmunoscintigraphy. However, the whole antibody has been reported to cause platelet aggregation. The object of the present study was to determine the effects of the F(ab')2 and Fab' fragments of P256 on human platelets in vitro. Gel-filtered platelets were prepared from citrated venous blood, and aggregation was studied at 37 degrees C using the method of Born. The whole antibody caused aggregation over the concentration range 10(-9)-10(-7) M, with a maximum of 70% aggregation. The F(ab')2 fragment was less potent with a maximum response of only 45%. The monovalent Fab' fragment caused no aggregation at concentrations up to 10(-7) M. However, binding studies with 111In-labelled monovalent Fab' fragment demonstrated saturable displaceable binding (Kd = 9.1 x 10(-9) M). Aggregation induced by the divalent forms of the antibody was partially dependent upon added fibrinogen. It is concluded that the monovalent Fab' fragment of P256 may be used in platelet-labelling studies without risk of inducing aggregation irrespective of concentration. The whole antibody, or its divalent F(ab')2 fragment, may also be used provided their concentrations are kept below 10(-9) M.

Antibodies, Monoclonal↗
PubMed1988

Appropriate selection of background for 99Tcm-DTPA renography.

Since 99Tcm-DTPA is diffusible and not significantly protein bound in plasma, it rapidly enters the extravascular space following injection. Therefore, during the first few minutes of the DTPA renogram, the period on which the measurements of individual kidney glomerular filtration rate and differential function are based, background activity comprises a rising extravascular signal and a falling intravascular signal. The aim of this study was to measure the ratio of these two signals in background present within the renal region of interest (ROI) and compare it with the ratio in a background ROI. An appropriate background ROI is one in which the ratio is equal to that in background in the renal ROI. To pursue this aim, we quantified the rates of change of the intravascular and extravascular activities in background and, by comparing them with the rate of increase of filtered activity, expressed them as GFR equivalents (the intravascular being negative). It is impossible, from a single renogram, to separate the rising extravascular signal from the signal due to filtered activity, and therefore impossible to quantify the extravascular GFR equivalent present in background within the renal ROI. We therefore studied six patients undergoing bone marrow transplantation before and after cyclosporin treatment. By comparing the dynamic renographic data between the two sequential studies, the substantial fall in GFR (from 107 +/- 12 S.D. to 49 +/- 7 ml min-1) permitted separate quantification of the extravascular GFR equivalent in the renal ROI in both studies. Three of the patients were studied on a third occasion after cyclosporin. In two, GFR remained low and these studies were paired with corresponding baseline studies, while in the other it increased and this was compared with the nephrotoxic study, giving a total of nine paired studies between which GFR changed. The ratio of intravascular to extravascular GFR equivalents in a background ROI placed above the kidney was considerably greater, and in a background ROI below the kidney considerably less, than that in the renal ROI. A background ROI which was the difference between the renal ROI and a perirenal ROI, 2 pixels outside the renal ROI along the horizontal and 1 pixel outside along the vertical, gave a ratio almost identical to that of the background within the renal ROI (renal ROI ratio:background ROI ratio = 1.09 +/- 0.17 S.D., n = 18).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Pelviureteric junction obstruction. The value of a post-micturition view in 99mTc DTPA diuretic renography.

Eighty-one 99mTc DTPA renograms were performed in 31 children who had previously undergone pyeloplasty for pelviureteric junction obstruction (PUJ). A post-micturition image following a diuretic stimulus excluded obstruction in 50% of the patients in whom the frusemide T75 was abnormally prolonged beyond 10 min. Evaluating the 99mTc DTPA renogram and the response to a diuretic without both changing the patient's position and ensuring an empty bladder may lead to incorrect diagnosis of PUJ obstruction.

Follow-Up Studies↗
PubMed1988

Inflammation: imaging with Tc-99m HMPAO-labeled leukocytes.

Leukocytes labeled with technetium-99m hexamethylpropyleneamine oxime (HMPAO) were used in 100 patients: 32 with suspected inflammatory bowel disease, 17 with fever of unknown origin, 21 with suspected abdominal sepsis, 20 with suspected bone sepsis, seven with bronchiectasis, and three with recent myocardial infarction. The distribution of activity in patients subsequently shown not to have inflammatory bowel disease was similar to that previously described for indium-111-labeled leukocytes. However, in this study, activity was also seen in the kidneys and bladder and occasionally the gallbladder on both early (1-3 hours) and late (24 hours) views, and in the colon in late views. Migration of Tc-99m-labeled granulocytes was seen in inflammatory disease as early as 30 minutes after injection, while normal bowel activity was not seen before 4 hours. The sensitivity of Tc99m-labeled leukocytes in the detection of inflammation was 100%, the specificity was 95%.

Colitis↗
PubMed1987

Indium-111-labelled granulocyte accumulation in respiratory tract of patients with bronchiectasis.

18 patients with severe bronchiectasis and persistent purulent sputum production were investigated, by the use of gamma scans, between acute exacerbations of their symptoms to determine localisation and traffic of 111In-labelled granulocytes in the lungs. Labelled granulocytes appeared in the respiratory tract of 16 patients within 24 h of their injection. Uptake occurred almost exclusively in areas demonstrated by computed tomography (CT) to be bronchiectatic. However, 111In uptake was not demonstrated in 21 of the 55 segments showing bronchiectasis on CT, and these were therefore thought to be not actively inflamed. The whole-body loss of radioactivity up to 4-7 days following injection of the labelled cells ranged from 0 to 53% and correlated with 24 h purulent sputum volume (r = 0.45, p less than 0.01) and with CT extent of moderate and severe bronchiectasis (r = 0.40, p less than 0.05), but not with overall CT extent of bronchiectasis, age, forced expiratory volume in one second, or duration of purulent sputum production in years.

Adult↗
PubMed1987

The symptomatic hip in childhood: scintigraphic findings in the presence of a normal radiograph.

The principal causes in children of a non-acute painful hip are Perthes disease and synovitis (irritable hip). The 99mTc methylene diphosphonate (MDP) bone scan appearances in Perthes disease are well-known; in synovitis, the hip may show a diffuse increase in activity or may be normal. The significance of bone scintigraphy in the clinical setting of non-acute hip symptoms with normal skeletal radiography has been evaluated in 36 symptomatic children. The mean duration of symptoms prior to scan was 3 months (range 1 week-17 months). On the basis of final diagnosis, established by clinical findings, bone scan, X-ray and follow-up, the children were divided into two groups: synovitis or Perthes disease. Of the 33 scans in the 32 children with synovitis, 18 were normal and 15 showed diffusely increased activity on the painful side. All four patients with Perthes disease had focal femoral head abnormalities in the painful hip. Of the 18 children with normal scans, none went on to develop a skeletal disorder. In children with hip pain of over 1 week's duration, the main value of the bone scan is the early detection of Perthes disease. Diffuse increased activity on the painful side suggests synovitis. A normal scan virtually excludes significant skeletal abnormality.

Child↗
PubMed1987

The value of indium-labelled leucocytes in clinical practice.

Following intravenous injection, autologous 111In labelled-leucocytes migrate to sites of inflammation, where they can be imaged with the gamma camera. The principle underlining the labelling technique is exposure of a population of leucocytes or purified granulocytes to a lipophilic 111In complex, such as 111In oxine or 111In tropolonate. As a result of cell activation, the in vitro manipulation to which the leucocytes are subjected modifies their biodistribution early after re-injection. Separation and labelling in plasma-enriched media, however, limits this activation and promotes early migration into inflammatory foci.

Humans↗
PubMed1987

Non-invasive measurement of renal blood flow with 99mTc DTPA: comparison with radiolabelled microspheres.

This technique for non-invasive measurement of renal blood flow is based on the principle of fractionation of cardiac output, and applicable with any recirculating gamma activity tracer. It effectively determines the count rate that would be recorded over the kidney if the tracer behaved like radiolabelled microspheres and was completely trapped in the kidney on first pass. After correction for kidney depth, the estimated first pass activity plateau, expressed as a fraction of the injected dose, is equal to the kidney's fraction of cardiac output. The principle of the technique was validated by comparison with renal blood flow based on radiolabelled microspheres. Nine separate comparisons were made in two anaesthetised dogs. A known dose of 99mTc radiolabelled microspheres (particle size 23-45 microns) was injected into the left ventricle and the count rate over each kidney recorded. A known dose of 99mTc diethylenetriaminepenta acetic acid (DTPA) was then given as an intravenous bolus and the data recorded dynamically with a gamma camera online to a computer. After subtraction of the stable signal arising from the preceding radiolabelled microspheres, the theoretical first pass activity plateau from the DTPA that would have been recorded if the DTPA, after reaching the systemic circulation, had behaved like radiolabelled microspheres and become completely trapped in the renal vascular bed, was estimated. Using doses based on syringe counts before and after injection the ratio of renal blood flow values given by the two techniques (DTPA:RLMS) was 1.14 (SD 0.22) for the left kidney and 1.1(0.17) for the right. Using doses based on whole body counts, corresponding ratios were 1.05(0.11) and 1.02(0.13).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Noninvasive measurement of blood flow and extraction fraction.

We describe the theory of a technique for the noninvasive measurement of organ blood flow which is based on the principle of fractionation of cardiac output and is applicable with any recirculating gamma emitting tracer. The technique effectively determines the count rate that would be recorded over the organ if the tracer behaved like radiolabelled microspheres and was completely trapped in the organ's vascular bed on first pass. After correction for organ depth, the estimated first pass activity plateau, expressed as a fraction of the injected dose, is equal to the organ's fraction of the cardiac output (CO). By extending the theory, organ extraction fraction of extractable tracers or mean transit time of nonextractable tracers can be measured. Renal blood flow (RBF) to the normal left kidney in 18 subjects without evidence of renal disease was estimated by the technique to be 10.4% CO (S.D. 1.2), for the right kidney 9.0% CO(S.D. 1.1), and for both, 19.4% CO (S.D. 1.5). In a separate series of eight patients, RBF values were highly reproducible when obtained on successive days (standard deviation of change: 0.67% CO for the left kidney, 0.63% CO for the right and 0.78% CO for both). The extraction fraction of DTPA (filtration fraction) was 8.5% (1.7) in the left kidney and 9.7% (2.1) in the right kidney. This parameter was less reproducible than RBF, with standard deviations of the changes equal to 1.17% for the left kidney and 1.31% for the right. Stable, well-functioning, renal allografts in children had a mean blood flow of 20.6% CO (S.D. 3.7). Transplant blood flow in eight patients with rejection was less than 5.2% CO. In patients without splenomegaly, splenic blood flow, splenic extraction fraction of sulphur colloid and splenic red cell mean transit time were 4.3% CO (S.D. 0.9), 41% (S.D. 13.8), and 36.9 s (S.D. 4.6), respectively.

Blood Circulation↗
PubMed1987

Surveillance for skeletal toxicity of children treated with etretinate.

Following recent reports of the development of skeletal abnormalities in patients treated with etretinate (Tigason), we have examined 19 children and adolescents on long-term treatment with etretinate, using 99mtechnetium methylene diphosphonate (99mTcMDP) whole body bone scans and musculoskeletal assessment. No significant bony abnormalities were detected. We believe that the available evidence does not warrant alarm, and that long-term etretinate therapy can probably be given with a low risk of musculoskeletal toxicity if certain precautions are taken, in particular the use of low maintenance dose levels, early investigation of symptoms of musculoskeletal pain or stiffness, and regular 99mTcMDP bone scans.

Adolescent↗
PubMed1987

Background in the 99mTc DTPA renogram: analysis of intravascular and extravascular components.

Individual kidney glomerular filtration rate (IKGFR) was calculated from the upslope of the 99mTc-diethylenetriamine pentaacetic acid (DTPA) renogram in ten children with a normal solitary kidney (on the right in five and on the left in five). By using a method of renogram analysis that is independent of the intravascular (IV) component of background (BG) activity, the IV and extravascular (EV) components of background were separately quantified in various regions in proximity to the nephrectomy site. The size of the IV compartment was expressed as an absolute plasma volume (PV-BG), and that of the EV compartment was expressed as a "GFR equivalent," i.e., the undirectional rate of fluid transfer from the IV to EV spaces in ml per min (GFR-BG). The region areas from which these parameters were calculated were normalised to the area projected by the solitary kidney. In a region centred over the lower pole of the imagined absent kidney, PV-BG was 129 +/- 7 ml (SE) and GFR-BG was 28 +/- 1.8 ml per min. The corresponding values centred over the liver/spleen on the nephrectomised side were 353 +/- 24 ml and -2 +/- 2.9 ml per min, respectively. PV-BG, but not GFR-BG, was significantly higher over the liver (397 ml and -6.8 +/- 1.5 ml per min) compared with the spleen (287 ml, P less than .05; and 4.5 +/- 3.2 ml per min, P greater than .05). PV-BG and GFR-BG in a region placed over the centre of the nephrectomy site were intermediate between those superior and inferior: 231 +/- 17 ml and 15 +/- 2.7 ml per min, respectively. The IV signal rises while the EV falls during the second phase of the renogram. In the analysis of the renogram during this phase, therefore, background should be based on both supra- and subrenal regions of interest.

Child↗
PubMed1986

Imaging thrombus with radiolabelled monoclonal antibody to platelets.

Indium-111-hydroxyquinoline labelled platelets, though useful in the detection of thrombus, have not gained widespread use owing to the time and technical skill required for their preparation. A study was therefore conducted evaluating a new method of imaging thrombus with platelets radiolabelled with a 111In labelled monoclonal antibody, P256, directed to the platelet surface glycoprotein complex IIb/IIIa. When the number of receptors occupied by P256 was less than 3% of the total available on the platelet surface platelet function, as assessed by platelet aggregometry, was undisturbed. P256 was radiolabelled with 111In using diethylenetriaminepenta-acetic acid, which achieved a specific activity of 185 MBq (5 mCi)/mg. No impairment of immunoreactivity was detected at this specific activity. Platelets were labelled with radiolabelled monoclonal antibody in vitro in two patients at a receptor occupancy of 6% and in vivo--that is, by direct intravenous injection of P256--in six patients at a receptor occupancy of 1%. In vivo recovery and biodistribution kinetics suggested that after in vitro labelling platelets were minimally activated. The 111In kinetics recorded after intravenous P256 suggested rapid and efficient radiolabelling of platelets and gave no indication of platelet activation. Of the six patients who received intravenous P256, three had documented thrombus, two of whom gave positive results on P256 platelet scintigraphy. The third subject had chronic deep venous thrombosis and was scintigraphically negative. Imaging thrombus using a radiolabelled monoclonal antibody directed to platelets appears to offer great potential as a simple, non-invasive approach to the diagnosis of thrombosis.

Animals↗