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Biomedical subjects

A M Peters

Publications and source records attributed to A M Peters.

At least 199 records · Page 11Linked to original sources

Multiple congenital abnormalities identifiable on 99Tcm HIDA scan.

We present a case in which three congenital abnormalities, in separate organ systems, were identifiable on a 99Tcm HIDA scan. The patient probably had Ivemark syndrome with dextrocardia (confirmed by chest radiograph), horseshoe kidney (confirmed by 99Tcm DTPA scintigraphy), and biliary atresia (confirmed on the HIDA scan). He also probably had asplenia, as suggested by the HIDA scan, although this was not confirmed.

Abnormalities, Multiple↗

The transition from optional to required subjects.

We propose (contra Hyams, 1986) that the optional subject phenomenon in early child language arises because children have not yet acquired the morphological elements (primarily modals and tense) necessary to distinguish Subject-Taking (ST) verbs (e.g. finite verbs) from their non-Subject-Taking (NST) counterparts (e.g. infinitives). Unaware of this distinction, children are able only to observe that verbs sometimes occur with subjects and sometimes without. We show that our proposal makes a number of developmental predictions which we then test with the help of longitudinal data from three children. We conclude that: (1) There is no systematic morphological distinction between ST and NST verbs during the optional subject stage (OSS). (2) The emergence of the distinction between ST and NST verbs is gradual rather than sudden. (3) There is variation from child to child in terms of which morphologically-defined subclass of verbs is first recognized as subject-taking. (4) There is no link between the emergence of modals or contracted copulas and the end of the OSS.

Child, Preschool↗

Solute transfer into the extravascular space: comparison of two non-invasive measurement techniques.

Little clinical attention has been paid to the quantification of microvascular permeability to small hydrophilic solutes, probably because of a paucity of non-invasive techniques. We describe a technique using the gamma camera which measures the clearance of 99mTc DTPA, a molecule similar in size to sucrose, from the intravascular to the extravascular space in the lumbar tissues below the kidneys. This regional clearance (PSr) is analogous to the permeability-surface area (PS) product, a well established concept for describing solute transfer across the capillary. We found a value in subjects with normal renal function of 1.0 (SD 0.2) ml.min-1.100 ml-1 tissue, which is broadly similar to the values anticipated from published values of the extraction fraction of 51Cr EDTA and plasma flow of resting human skeletal muscle. We also describe an index, the t95, of whole body microvascular permeability. This is the time at which the second exponential of the bi-exponential plasma 99mTc DTPA clearance curve becomes equal to 95% of the total curve. The index reflects the rate of equilibration of DTPA between intravascular and extravascular spaces, and should reflect whole body microvascular permeability. The t95 showed a significant inverse correlation with regional clearance (t95 = -12 PSr + 98 min; r = -0.61; n = 60; p less than 0.001) confirming their mutual dependence on capillary DTPA transfer. These non-invasive techniques, with their advantages of simplicity, could prove useful in a variety of clinical settings.

Capillary Permeability↗

Noninvasive measurement of microvascular permeability to small solutes.

Quantification of microvascular permeability to diffusible hydrophilic solutes has received little attention in a clinical setting, probably because of a lack of noninvasive techniques. We describe a gamma camera technique which measures the clearance of 99Tcm-DTPA from the intravascular to extravascular space in extra-renal regions of interest over the lumbar region, the tissues within which being predominantly skin and muscle. This regional clearance (PSr), normalized to 100 ml of tissue, represents the permeability-capillary surface area (PS) product, a classical concept for describing solute transfer across the capillary. We found a mean value in 14 patients with normal renal function of 1.0 (S.D. 0.2) ml/min/100 ml of tissue, which is broadly similar to values anticipated from published values of 51Cr-EDTA extraction fraction (in a single pass) in human skeletal muscle and resting muscle plasma flow. The technique also generates the plasma volume (tPV) within this subrenal tissue, which we found to be 5.0 (2.0) ml/100 ml. In an attempt to reproduce an index of extraction fraction we also calculated the ratio PSr:tPV and this was 0.23 (0.08) min-1. This approach could prove useful in a variety of clinical settings.

Capillary Permeability↗

Effects of posture on the distribution of pulmonary ventilation and perfusion in children and adults.

In the adult the distributions of ventilation and of perfusion show the same directional dependence on gravity. In children, however, the distribution of ventilation in response to gravity is the reverse of that seen in adults. The aim of the current study was to determine whether perfusion showed the same reversal in children or followed the adult pattern. Distribution of perfusion was measured with intravenous technetium-99m macroaggregated albumin and distribution of ventilation with inhaled krypton-81m. Eighteen children and seven adults were studied; they had been referred for lung scanning for various respiratory problems. The effect of gravity was examined by giving aliquots of macroaggregated albumin and 81mKr by inhalation to the subject in the supine and the lateral decubitus position. Counts in the dependent lung were compared with those in the upper lung. The dependent lung in the lateral decubitus position received more of the total perfusion than it did in the supine position in seven children with a normal chest radiograph (mean 7.0%, range 4.8-10.9% more) and in 11 children with an abnormal radiograph (mean 3.4%(0.1-10.0%)). Ventilation, however, changed in the opposite direction, falling by 7.1% (-3.2% to -12.8%) in five children with a normal chest radiograph and 11.2% (-2.8% to -19.3%) in eight children with an abnormal radiograph. Fractional V/fractional Q (an index of the ventilation:perfusion ratio) decreased in the dependent lung in the children when they moved from the supine to the decubitus position. The same directional change was recorded in adults, but it was significantly less than in the children, irrespective of whether the chest radiograph was abnormal. In children and adults with various respiratory problems the effect of posture on the distribution of perfusion is similar.

Adult↗

Filtration fraction.noninvasive measurement with Tc-99m DTPA and changes induced by angiotensin-converting enzyme inhibition in hypertension.

Using a recently described new technique, individual kidney filtration fraction was measured from the first 3 min of the Tc-99m DTPA renogram in a series of 11 subjects without evidence of renal disease and in 23 patients with hypertension. Fourteen of these hypertensives had angiographic evidence of renal artery stenosis (RAS) but only 2 had proven renovascular hypertension (RVH). In addition, renal blood flow (RBF), expressed as a fraction of cardiac output, was measured from the first pass time activity curves following bolus injection of Tc-99m DTPA, and individual kidney glomerular filtration rate (IKGFR) was measured from the subsequent plasma Tc-99m DTPA clearance and renographic divided function. An estimation of filtration fraction based on these measurements of RBF and IKGFR correlated rather poorly with that directly based on the renogram, although both showed directionally similar changes in the hypertensive patients following inhibition of angiotensin-converting enzyme (ACE) with captopril. Filtration fraction by both estimates fell significantly after ACE inhibition in patients with RAS and essential hypertension, while RBF increased. IKGFR showed no change in essential hypertension or in hypertensive patients with RAS but fell sharply in 3 renal units in 2 patients with RVH. This renographic method for measuring filtration fraction is worthy of further elaboration and might be a simple and useful discriminator of RVH in a hypertensive population.

Adult↗

Spontaneous abrupt changes in the distribution of ventilation: a cause for apparent mismatching on ventilation/perfusion scintigraphy.

A defect seen in the perfusion scan in a region of lung that is normally ventilated is usually interpreted as indicating pulmonary vascular disease. Since the distribution of 99Tcm macro-aggregated albumin (MAA) represents the distribution of perfusion (Q) only at the time of MAA injection, the assumption is required that the distribution of ventilation (V) remains unchanged between MAA injection and the commencement of imaging. We report the V/Q scintigraphic findings in six patients (including four children), in whom this assumption could not be sustained. Thus ventilation imaged with 81Krm was seen to change during image acquisition in lobes that showed perfusion abnormalities. In some, but not all, views the appearances were typical for pulmonary vascular disease, which might easily have been misdiagnosed if the changes in the distribution of ventilation had not announced themselves by occurring during image acquisition. A ventilation image obtained immediately before injection of 99Tcm-MAA may be useful.

Child↗

Sequential imaging of post-operative thrombus using the In-111-labelled platelet-specific monoclonal antibody P256.

Eleven patients undergoing total hip replacement were studied by radioimmunoscintigraph for development of postoperative thrombus. Images were obtained using the 111In-labelled Fab' fragment of a monoclonal antibody (P256) directed against human platelets. Six patients showed focal accumulation of radioactivity in the lower limbs. Three of these had contrast venograms that were all positive for thrombus. Two of these six patients showed evidence of pulmonary localization of P256-Fab' and this correlated with positive ventilation/perfusion scintigraphy in one of the patients. Sequential imaging with 111In-P256 Fab' not only established a diagnosis of deep venous thrombus but also provided useful information regarding its natural history.

Aged↗

Two routes for 99mTc-DMSA uptake into the renal cortical tubular cell.

Critical factors determining the renal handling of 99mTc-dimercaptosuccinic acid (DMSA) are protein binding in plasma and the renal 99mTc-DMSA extraction efficiency. Comparison of the count rate over soft tissue with that over the cardiac blood pool about 1 h after injection demonstrated that 99mTc-DMSA is not exclusively an intravascular label. 99mTc-DMSA was 76% protein bound in plasma as demonstrated by HPLC and gel filtration. Assuming that the 24% that is not protein bound is filtered at the glomerulus, the renal extraction efficiency of 99mTc-DMSA by glomerular filtration is about 5%. Since the total renal extraction efficiency was also found to be about 5%, the majority of the activity that becomes fixed in the renal cortex arrives there as a result of filtration followed by tubular reabsorption rather than by direct extraction from peritubular blood. However, discordant changes in DMSA and DTPA uptake induced by captopril in renovascular hypertension (RVH) suggested that a minority of uptake was by direct peritubular extraction. This kinetic model was supported by indirect measurement of protein binding and extraction efficiency based on the kinetics of 99mTc-DMSA disappearance from plasma and kinetics of uptake in the kidneys. Furthermore, differential functional studies based on 99mTc-DMSA and 99mTc-DTPA before and after captopril in patients with RVH due to unilateral renal artery stenosis confirmed filtration followed by tubular reabsorption as the predominant route for DMSA uptake by the kidney.

Adult↗

Quantification of right to left shunt through pulmonary arteriovenous malformations using 99Tcm albumin microspheres.

Calculation of the right-to-left shunt through pulmonary arteriovenous malformations (PAVMs) is important in assessing the effect of therapeutic embolisation or surgical resection. Previously, complicated physiological techniques using radiolabelled inert gases or the 100% oxygen breathing method were required. We describe a new method for quantitating the systemic uptake of intravenously injected 99Tcm albumin microspheres (99Tcm MS) which reflects shunt fraction since these particles do not normally traverse the pulmonary capillary bed. Seven patients with PAVMs were studied and shunt values obtained using 99Tcm MS were validated by simultaneous measurement of shunt fraction using the 100% oxygen method. By comparing radioactive counts in the injection dose to subsequent counts in the right kidney, which was taken as an index of systemic activity, accurate quantification of right-to-left shunt over a wide range of values was obtained (correlation coefficient against 100% oxygen method r = 0.993). The comparison of right kidney counts with total lung counts and total lung counts with injected dose counts, also indicators of shunt fraction, correlated less well with the oxygen method (r = 0.942 and r = 0.88 respectively). Use of 99Tcm labelled microspheres allows simple and precise measurement of right-to-left shunt in patients with PAVMs during routine isotope lung scanning.

Adult↗

99Tcm-HMPAO labelled leucocytes: comparison with 111In-tropolonate labelled granulocytes.

The lipophilic complex, 99Tcm-hexamethylpropyleneamine oxime (HMPAO) is an efficient leucocyte label, and labels granulocytes with more stability than mononuclear leucocytes. The recovery of 99Tcm-HMPAO granulocytes, expressed as the percentage of injected granulocyte-associated activity circulating as granulocyte-associated activity 40-45 min after injection, was 37% (S.E. 3%), similar to the recovery of 111In-labelled granulocytes isolated and labelled in plasma using tropolone. The T1/2 of 99Tcm-HMPAO labelled granulocytes in blood was 4.4 h (S.E. 0.4 h), less than that of 111In-labelled granulocytes, although when a correction was made for 99Tcm elution, it was 6.4 h. The initial biodistribution of 99Tcm-labelled leucocytes was similar to 111In-labelled granulocytes, with a rapid initial lung transit, prominent splenic activity, bone marrow activity and minimal hepatic activity, although, unlike 111In, 99Tcm activity was also seen in urine, occasionally in the gallbladder, and, from about 4 h, consistently in the colon. Bone marrow activity was particularly prominent with 99Tcm. About 6% of 99Tcm was excreted in the faeces up to 48 h after injection, and about 17% in urine up to 24 h. The time-activity curves of reticuloendothelial activity up to 24 h were broadly similar for the two labelled cell preparations, and the differences that were observed can be explained on the basis of a higher rate of 99Tcm elution. Clinical information given by the two agents was similar in 27 of 30 patients who received both. Of the three who gave different information, one received 111In-labelled granulocytes which were considered to be functionally suboptimal and two, with inflammatory bowel disease, showed different distributions of abnormal bowel activity. We conclude that with respect to granulocyte kinetics and clinical data, 99Tcm-HMPAO labelled leucocytes are comparable with 111In-tropolonate labelled granulocytes.

Colitis, Ulcerative↗

Background in 99Tcm DTPA renography evaluated by the impact of its components on individual kidney glomerular filtration rate.

Following injection for renography, 99Tcm-labelled diethylenetriamine-pentacetic acid (DTPA) rapidly enters the extravascular space. Background therefore comprises two components, a falling intravascular signal and an extravascular signal which initially rises. We estimated the relative magnitudes of these two components in terms of their impact on the calculation of differential renal function and individual kidney glomerular filtration rate (IKGFR) from the second phase of the 99Tcm-labelled DTPA renogram in 56 paediatric kidneys. We expressed each of the two background signals as a GFR equivalent. The GFR equivalent of the intravascular signal recorded from a peri-renal background region of interest (ROI), scaled by a factor equal to the ratio of the pixel numbers in the renal and background ROIs, was -39 (S.D. 14) ml min-1. The GFR equivalent of the extravascular signal was smaller than this and opposite to it at 23 (S.D. 10) ml min-1, giving a median ratio for the two equivalents of -1.68. Because of the opposing effects of the two background components on the second phase of the renogram, techniques recently described for the quantification of IKGFR from the renogram, and which eliminate the intravascular component, offer no theoretical advantage over a method of analysis which uses 'direct' subtraction of the total background signal. In practice, however, these new techniques are superior in their handling of 'noisy' data, consistently giving a lower coefficient of variation in their estimation of IKGFR.

Child↗

Use of an anti-platelet monoclonal antibody F(ab')2 fragment for imaging thrombus.

Ten patients with suspected thrombus have been studied using 111In-labelled F(ab')2 fragments of P256, a monoclonal antibody which recognizes an epitope on the platelet membrane glycoprotein protein IIb/IIIa complex. The F(ab')2 fragment was radiolabelled with 111In via diethylenetriaminepenta-acetic acid to give a specific activity of up to 190 MBq (5 mCi) mg-1 without impairment of immunoreactivity. In vitro platelet aggregation studies showed that the F(ab')2 fragment caused less platelet aggregation than the whole antibody on a molar ratio and was without significant effect upon the sensitivity of platelets to a range of aggregating agents. Platelets were labelled in ten patients by intravenous injection of approximately 100 micrograms P256 F(ab')2. Of the ten patients studied, six showed localization of activity consistent with platelet accumulation. Localization was clearly seen when associated with thrombus of the lower limbs (three patients: deep vein thrombosis; one patient: aortofemoral graft), and was apparent although less marked in two other cases, one of aortic aneurysm and one of carotid stenosis. Use of radiolabelled P256 F(ab')2 offers a means of non-invasive detection of thrombus which, from in vitro studies, would appear to have less direct effect on platelet behaviour than the whole antibody.

Antibodies, Monoclonal↗

Osteomyelitis.

The use of 111In-labelled granulocyte scintigraphy is recognized as a reliable method for detecting osteomyelitis and has similar sensitivity and significantly increased specificity compared to bone scintigraphy and 67Ga studies. Recent published work using pure granulocytes labelled with 111In tropolonate to detect osteomyelitis resulted in sensitivity of 100% and specificity of 92%. 99Tcm as an alternative granulocyte label offers advantages of convenience, lower radiation dose and higher image resolution. We have scanned 20 patients with suspected osteomyelitis using autologous granulocytes labelled with 99Tcm hexamethylpropyleneamineoxime (HMPAO), 12 of whom had prosthetic joints. The scan results were correlated with clinical, radiographic, microbiological and histological findings. Sensitivity was 100% and specificity was 93% which compares favourably with results obtained using 111In-labelled granulocytes. We believe that labelled granulocyte scintigraphy is a useful investigation in the diagnosis of osteomyelitis and that 99Tcm HMPAO appears to be at least as useful as 111In as the labelling agent.

Granulocytes↗