Search PubMed⌕ Search

Biomedical subjects

A M Peters

Publications and source records attributed to A M Peters.

At least 91 records · Page 5Linked to original sources
PubMed1996

The kinetics of MHC class I and class II expression in rat renal allografts.

We have used in vivo localization of radiolabeled antibodies in a rat renal transplant model to compare the level of induction of major histocompatibility complex (MHC) class I and class II molecules in grafts undergoing rejection with grafts in which rejection was modified by cyclosporine (CsA). MHC class II expression increased in rejecting grafts, peaking on day 4, whereas a later rise in CsA-treated grafts was noted. The use of donor-specific antibodies demonstrated that this was due, in part, to a rise in class II of donor origin. No major differences in MHC class I levels were noted between the two groups until after day 4, when very little antibody localization was seen in the rejecting group. Our results suggest that therapeutic doses of CsA may not prevent the upregulation of class II that occurs during rejection, and that levels of class II are not of prognostic value in kidney transplantation.

Animals↗
PubMed1996

Use of a radiolabeled monoclonal antibody against E-selectin for imaging of endothelial activation in rheumatoid arthritis.

OBJECTIVE: To determine the potential of 111In-labeled anti-E-selectin monoclonal antibody (MAb) to image localized endothelial activation in rheumatoid arthritis (RA). METHODS: Fourteen patients with RA were studied after intravenous administration of 111In-labeled F(ab')2 fragments of MAb against the cytokine-inducible endothelial cell activation antigen E-selectin (MAb 1.2B6). To compare uptake of 1.2B6 with that of nonspecific immunoglobulin, 111In-labeled polyclonal human immunoglobulin (HIG) was separately administered to 6 of these patients and the relative uptake of each tracer was determined. RESULTS: Prominent and discrete uptake of the radiolabeled MAb 1.2B6 was clearly visible in inflamed joints of all patients. Compared with 111In-HIG, 111In-1.2B6 provided superior images in terms of sensitivity and image intensity. Furthermore, the distribution of uptake in inflamed joints was different for the 2 tracers, with 1.2B6 showing a more focal localization in synovium. CONCLUSION: This study demonstrates that it is possible to objectively assess E-selectin expression on activated endothelium in vivo in patients with RA, using a radiolabeled MAb. This technique has considerable potential for monitoring disease activity and response to therapy in inflammatory diseases.

Aged↗
PubMed1996

Detection and quantification of protein-losing enteropathy with indium-111 transferrin.

Localisation and quantification of protein loss in protein-losing enteropathy (PLE) is useful in the clinical management of hypoalbuminaemia. Indium-111 transferrin offers the opportunity of combining localisation and quantification using a single agent. Twenty-five studies were performed in 23 patients with suspected PLE: 111In-transferrin was prepared by incubating autologous cell-free plasma with 111In chloride in vitro for 15 min. Protein loss was quantified by comparing whole-body counts recorded with an uncollimated gamma camera at 3 h and 5 or 6 days after injection of 111In-transferrin. Gamma camera imaging performed at 3 and 24 h after injection demonstrated a site of protein loss in 15 studies. Whole-body 111In excretion was abnormally elevated in 13 of these, ranging from 16% to 34% (normal <10%), was not assessed in one and was less than 10% in a patient with carcinoid syndrome. In the ten studies that were negative on imaging, whole-body 111In excretion was normal in nine and elevated at 22% in a further patient with carcinoid syndrome. Overall, the mean whole-body 111In excretion in studies with positive imaging was 21.4% (SD 6.1%) (n=14), significantly higher (P<0.01) than in studies with negative imaging, in which it was 7.5% (SD 6.7%) (n=10). This technique should be useful for the combined approach of localising and quantifying protein loss in PLE.

Adult↗
PubMed1996

Glomerular filtration rate in relation to extracellular fluid volume: similarity between 99mTc-DTPA and inulin.

The rate constant (alpha2) of the terminal exponential of the technetium-99m diethylene triamine penta-acetic acid (DTPA) plasma clearance curve is close to the ratio of glomerular filtration rate (GFR) to extracellular fluid volume (ECV) and is therefore a convenient, already normalised, measure of filtration function. Since alpha2 depends on the distribution volume of the tracer, our aim was to compare alpha2 from inulin and 99mTc-DTPA and also to compare the equilibration kinetics of the two filtration markers. Fifty millilitres of 99mTc-DTPA (250MBq) and inulin (10%), mixed in the same syringe, were given by intravenous injection in 15 patients undergoing routine 99mTc-DTPA renography for a variety of clinical indications. Frequent antecubital venous blood samples were taken up to about 4h after injection to construct plasma clearance curves from which GFR, ECV and GFR/ECV (i.e. the reciprocal of mean transit time through the distribution volume) were calculated. 99mTc-DTPA/inulin concentration ratio curves were also constructed after normalisation to the ratio in the syringe. GFR given by the two markers correlated closely (DTPA=0.98.inulin-0.4ml/min; r=0.98). 99mTc-DTPA had the same distribution volume as inulin, had a similar transit time through it and gave the same value of alpha2 (r=0.98). GFR/ECV from 99mTc-DTPA accordingly correlated closely with GFR/ECV from inulin (DTPA=0.75.inulin+0.99 ml/min; r=0.95). Even though the distribution volumes and the times to equilibration (i.e. to reach the terminal exponential) were similar, the distribution volume of 99mTc-DTPA at about 10min after injection was, after subtraction of the plasma volume, about twice that of inulin. We confirm the validity of 99mTc-DTPA for measuring GFR. alpha2 is a convenient measure of GFR, can be based on the terminal exponential of inulin of 99mTc-DTPA curves and can be converted to GFR/ECV with an appropriate scaling factor. The kinetics or the two clearance curves with respect to anatomical correlates of the exponentials and the rates of diffusion throughout the respective distribution volumes requires further study.

Extracellular Space↗
PubMed1996

Echo-planar microscopy of porous rocks.

A modified version of the echo-planar imaging sequence incorporating multiple 180 degrees RF pulses (PEPI) has been implemented at 11.7 T and used to generate high resolution images of porous solids. By preceding the PEPI sequence with an inversion recovery or flow-encoding sequence, rapid T1, and velocity mapping is possible in the microscopic domain.

Echo-Planar Imaging↗
PubMed1996

Relationship between granulocyte activation, pulmonary granulocyte kinetics and alveolar permeability in extrapulmonary inflammatory disease.

1. The aim of the study was to examine the relationship between granulocyte activation, pulmonary intravascular granulocyte transit, pulmonary extravascular granulocyte migration and lung injury in patients with systemic conditions (bone marrow transplant recipients, inflammatory bowel disease and systemic vasculitis) in which abnormalities of pulmonary granulocyte traffic have previously been reported. 2. A double 111In-99mTc granulocyte labelling technique was used for quantification of granulocyte kinetics in 23 patients, of whom five were control patients. The pulmonary vascular granulocyte pool was measured from dynamic data centred on the 99mTc signal and expressed as a percentage of the total blood granulocyte pool. Granulocyte migration was quantified on 24 h images using the 111In signal. Granulocyte activation was measured as the percentage of cells showing a change in shape. The clearance rate of an inhaled aerosol of 99mTc-diethylenetriaminepenta-acetic acid (DTPA) was used as a marker of lung injury. 3. Pulmonary granulocyte pool, migration, activation and aerosol clearance, although highly variable in the patient groups, were, in general, elevated compared with the controls. 4. Granulocyte activation correlated with pulmonary granulocyte pool (Rs = 0.72, n = 22, P < 0.01), while the t1/2 of DTPA clearance correlated with migration (Rs = -0.84, n = 17, P < 0.01). Fifteen patients had an expanded pulmonary granulocyte pool, of whom six with no evidence of migration, had a normal DTPA clearance, while nine, who had an abnormal migration signal, had an accelerated DTPA clearance. The pulmonary granulocyte pool in these nine was significantly higher than in the six without a migration signal. 5. Activation of granulocytes results in delayed transit through the lung vasculature. With increasing margination, granulocytes migrate into the lung interstitium and injure the lung. An increased intravascular pool does not by itself lead to lung injury.

Adult↗
PubMed1996

Characterization of E-selectin expression, leucocyte traffic and clinical sequelae in urate crystal-induced inflammation: an insight into gout.

The self-limiting response to urate crystals allows the exploration of events involved in both the onset and resolution of gout. Using i.v. injected radiolabelled anti-E-selectin monoclonal antibody 1.2b6 together with differentially radiolabelled neutrophils, mononuclear cells and albumin, we have characterized the expression of E-selectin in relation to leucocyte traffic, microvascular permeability and clinical sequelae following intracutaneous injection of monosodium urate crystals. We found that the inflammatory response in this model involved several distinct phases. First, E-selectin expression increased over 2-6 h in the context of increases in neutrophil and mononuclear cell accumulation, and albumin leakage. Secondly, leucocyte accumulation rapidly declined despite persisting E-selectin expression. Thirdly, E-selectin expression peaked at approximately 8 h and then fell despite an increase in clinically detectable erythema and induration. Lastly, these clinical manifestations of inflammation resolved despite the continued presence of urate crystals in the tissues. The further dissection of mechanisms regulating these phases will lead to a better understanding of events in both the pathogenesis and resolution of gout. Of broader significance, this inflammatory model may yield information about the protective events that underly resolution of inflammation, and provide insights into factors which determine chronicity.

Albumins↗
PubMed1996

Case report: the need for caution when using the spleen to assess renal blood flow in renography.

Visual assessment of renal blood flow from renography is usually achieved by comparing the count rate from the kidney with that of the spleen during the first pass of the radiopharmaceutical agent. This is not justifiable if splenic blood flow is abnormal. In nine subjects without evidence of renal or other significant disease, the mean ratio of the slopes of the first pass curves over the left kidney and the spleen was 1.7 (SD 0.32). However, an additional patient, a 67-year-old female with type-II cryoglobulinaemia, illustrated the need for caution when using this approach. Her splenic blood flow was significantly elevated, resulting in a kidney/spleen slope ratio of only 0.66, even though her renal function was thought to be normal.

Aged↗
PubMed1996

Case report: imaging of central nervous system sarcoidosis with gallium-67 single photon emission computed tomography.

Involvement of the nervous system is an uncommon and underdiagnosed complication of sarcoidosis. We used gallium single photon emission computed tomography (SPECT) to define areas of meningeal involvement in a patient with neurosarcoidosis. This technique may be of value in the assessment of patients with sarcoidosis and suspected central nervous system involvement.

Adult↗
PubMed1996

Short communication: renal function and the excretion of contrast agents.

The renal excretion of intravascular iodinated X-ray and gadolinium chelate MR contrast is examined theoretically. An expression is derived for the proportion of an administered dose of such an agent excreted in any given time in the face of varying levels of renal function. It is shown that a family of curves may be generated from which an estimate of this proportion for any time may be made. Some circumstances in which such knowledge may be useful are briefly discussed.

Algorithms↗
PubMed1996

Single-chain Fv radioimmunotargeting.

The availability of engineered antibody species has catalyzed new developments in radioimmunotargeting. This chapter summarized recent studies of single-chain Fv (sFv) proteins, which are minimal antibody binding sites engineered as single polypeptide chains. The single-chain Fv can be as small as 26 kDa monomers or may be engineered as larger fusion proteins designed to self-associate into dimeric or multimeric species. They typically exhibit rapid clearance that results in high targeting specificity within a matter of hours. We have compared different modes of administration to allow further manipulation of their biodistribution and targeting properties. Results of the present study comparing intravenous (i.v.) and intraperitoneal (i.p.) administration show comparable long-term retention in circulation, but the i.v. route showed an initially high peak blood level while i.p. injection did not. As with a single sFv dose, repeated bolus injections of sFv attained high target-to-background ratios, whereas continuous sFv infusion reached a steady state level of free sFv in blood and kidney that exceeded that in tumor xenografts. We observed improved localization of radioiodinated sFv in tumor xenografts if the radioiodine label resisted dehalogenation from the protein, which was accomplished, for example, through conjugation of a para-131I-benzoyl group to Iysyl epsilon-amino groups of the protein. Modification of the sFv by genetic incorporation of a cysteinyl peptide (to form sFv') provided a chelation site for radiometals that simplified incorporation of 99mTc with the opportunity for improved diagnostic imaging in cancer and other diseases. Therapeutic applications of sFv radioimmunotargeting could rely on sFv' complexed to 186Re or 188Re. Engineering sFv of sFv' with increased antigen-binding affinity and appropriately manipulating their mode of administration should promote sustained tumor retention conducive to clinically useful therapeutic indices.

Animals↗
PubMed1995

Radiometal labeling of recombinant proteins by a genetically engineered minimal chelation site: technetium-99m coordination by single-chain Fv antibody fusion proteins through a C-terminal cysteinyl peptide.

We describe a method to facilitate radioimaging with technetium-99m (99mTc) by genetic incorporation of a 99mTc chelation site in recombinant single-chain Fv (sFv) antibody proteins. This method relies on fusion of the sFv C terminus with a Gly4Cys peptide that specifically coordinates 99mTc. By using analogues of the 26-10 anti-digoxin sFv as our primary model, we find that addition of the chelate peptide, to form 26-10-1 sFv', does not alter the antigen-binding affinity of sFv. We have demonstrated nearly quantitative chelation of 0.5-50 mCi of 99mTc per mg of 26-10-1 sFv' (1 Ci = 37 GBq). These 99mTc-labeled sFv' complexes are highly stable to challenge with saline buffers, plasma, or diethylenetriaminepentaacetic acid. We find that the 99mTc-labeled 741F8-1 sFv', specific for the c-erbB-2 tumor-associated antigen, is effective in imaging human ovarian carcinoma in a scid mouse tumor xenograft model. This fusion chelate methodology should be applicable to diagnostic imaging with 99mTc and radioimmunotherapy with 186Re or 188Re, and its use could extend beyond the sFv' to other engineered antibodies, recombinant proteins, and synthetic peptides.

Amino Acid Sequence↗
PubMed1995

Technetium-99m and indium-111 double labelling of granulocytes for kinetic and clinical studies.

A new technique of labelling granulocytes with both technetium-99m hexamethylpropylene amine oxime (HMPAO) and indium-111 in a single protocol was developed in order to exploit the advantages of each radiolabel in clinical and investigative studies. Fourteen patients were included in this prospective study. Granulocytes were labelled with both 111In-tropolonate and 99mTc-HMPAO. In vitro shape change assay and in vivo distribution and recovery studies were performed to assess the activation of and damage to these cells due to the labelling procedure. The comparative kinetics of 111In and 99mTc in the blood, liver, spleen, and bone marrow were studied by blood sampling and dual radionuclide imaging early (1 h) and late (24 h) after injection. The functional integrity of the double-labelled granulocytes and the feasibility of the technique were investigated in 14 patients with a painful prosthetic hip due to causes other than infection. The efficiency of double labelling was 63% (SD 14%) for 111In and 39% (SD 12%) for 99mTc-HMPAO. In vitro granulocyte activation and ex vivo recovery values were comparable to those from single radionuclide labelling. No artefactual granulocyte sequestration was seen in the lungs or liver. The radioactivity was distributed between the liver, spleen and bone marrow and, to a lesser extent, the lung. Early 99mTc counts in the liver, spleen and bone marrow, in relation to background, were significantly higher than 111In counts while the reverse was seen in late images.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A simple method for measuring glomerular filtration rate in dogs.

A technique for measuring glomerular filtration rate (by six-sample plasma clearance) and extracellular fluid volume is described. The results obtained for glomerular filtration rat per extracellular fluid volume with a three blood sample technique are also presented. Concurrently with the blood sample techniques measuring plasma clearance, glomerular filtration rate per extracellular fluid volume was also measured using an external radiation detector and no blood samples. The validity of expressing glomerular filtration rate per extracellular fluid volume (rather than per body weight or surface area) and the clinical utility of the results obtained with the external radiation detector are discussed.

Animals↗
PubMed1995

Non-invasive measurement of microvascular permeability to a small solute in man: validation of the technique.

1. The purpose of the study was to evaluate a non-invasive technique for measurement of microvascular permeability to a small hydrophilic solute. 2. The technique measures the clearance of 99mTc-labelled diethylenetriaminepenta-acetic acid (99mTc-DTPA) from plasma into interstitial fluid in a limb after intravenous injection and uses a scintillation probe and a technique of graphical analysis called the Patlak plot, the uptake constant of which reflects 99mTc-DTPA transfer from plasma to interstitial fluid. Using deconvolution analysis, the retention function in the limb of intravenous 99mTc-DTPA was also measured. 3. The clearance values given by these two analytical techniques were compared with clearance from the same vascular bed after bolus femoral intra-arterial injection of 99mTc-DTPA. 4. Sixteen patients undergoing routine diagnostic arteriography were studied: six received sequential femoral intra-arterial injections of 99mTc-labelled human serum albumin (HSA) and 99mTc-DTPA, two received sequential intra-arterial and intravenous injections of 99mTc-HSA and eight received sequential intra-arterial and intravenous injections of 99mTc-DTPA. Tissue uptake and clearance were recorded from the limb with a scintillation probe and plasma clearance by arterial blood sampling. Tracer recirculation was addressed using a second scintillation probe over the contralateral limb. 5. After intra-arterial injection, 99mTc-HSA clearance was monoexponential, reflecting intravascular transit, and was completed by 2-5 min in seven subjects and in about 10 min in one. The corresponding 99mTc-DTPA clearance curves in the six subjects who also received intra-arterial DTPA were biexponential, analysis of which yielded a 99mTc-DTPA extraction fraction of about 0.6. By comparison with 99mTc-HSA clearance, the first exponential clearly corresponded to intravascular transit of unextracted 99mTc-DTPA. 6. In the eight patients given sequential intra-arterial and intravenous injections of 99mTc-DTPA, the second exponential recorded after intra-arterial injection, representing 99mTc-DTPA clearance from the interstitial fluid, agreed well with (a) the Patlak uptake constant recorded over the limb after intravenous injection, representing clearance from plasma into the interstitial fluid and (b) the retention function of 99mTc-DTPA in a limb calculated by deconvolution analysis. The mean clearance following intra-arterial injection (expressed in relation to extracellular fluid volume) was 9.6 (SD 2.4) ml min-1 100 ml-1, while the corresponding mean clearance after intravenous injection was 8.8 (2.1) ml min-1 100 ml-1 calculated by Patlak analysis and 10.5 (2.7) ml min-1 100 ml-1 by deconvolution analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Capillary Permeability↗
PubMed1995

Is computer-aided interpretation of 99Tcm-HMPAO leukocyte scans better than the naked eye?

In order to compare visual interpretation of inflammation detected by leukocyte scintigraphy with that of different computer-aided quantification methods, 34 patients (25 with ulcerative colitis and 9 with endoscopically verified non-inflamed colonic mucosa), were investigated using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) leukocyte scintigraphy and colonoscopy with biopsies. Scintigrams were obtained 45 min and 4 h after the injection of labelled cells. Computer-generated grading of seven colon segments using four different methods was performed on each scintigram for each patient. The same segments were graded independently using a 4-point visual scale. Endoscopic and histological inflammation were scored on 4-point scales. At 45 min, a positive correlation was found between endoscopic and scan gradings in individual colon segments when using visual grading and three of the four computer-aided methods (Spearman's rs = 0.30-0.64, P < 0.001). Histological grading correlated with visual grading and with two of the four computer-aided methods at 45 min (rs = 0.42-0.54, P < 0.001). At 4 h, all grading methods correlated positively with both endoscopic and histological assessment. The correlation coefficients were, in all but one instance, highest for the visual grading. As an inter-observer comparison to assess agreement between the visual gradings of two nuclear physicians, 14 additional patients (9 ulcerative colitis, 5 infectious enterocolitis) underwent leukocyte scintigraphy. Agreement assessed using kappa statistics was 0.54 at 45 min (P < 0.001). Separate data concerning the presence/absence of active inflammation showed a high kappa value (0.74, P < 0.001). Our results showed that a simple scintigraphic scoring system based on assessment using the human eye reflects colonic inflammation at least as well as computer-aided grading, and that highly correlated results can be achieved between different investigators.

Adolescent↗