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Biomedical subjects

A M Peters

Publications and source records attributed to A M Peters.

At least 73 records · Page 4Linked to original sources
PubMed1998

Appropriate background correction for DTPA aerosol clearance.

Measurement of the clearance rate of inhaled aerosols of 99mTc-diethylenetriamine pentaacetic acid (DTPA) from distal airway to pulmonary capillary is a sensitive technique for the detection of lung injury. As the solute diffuses across the blood-gas barrier, the concentration in circulating blood increases, giving rise to a background signal superimposed on the signal from residual DTPA in the airway. Background subtraction is conventionally based on the thigh, but this tissue has the disadvantage in that its composition, in terms of the relative volumes of its extracellular extravascular and intravascular compartments (a ratio of approximately 4:1), is quite different from that of the lung (<1:6). With comparison to the thigh, we examined alternative regions for background, liver, and cranium, which have extravascular-to-intravascular compartment ratios much closer to these for the lung, to determine the most appropriate background for correction of the pulmonary signal. From 1 min after intravenous injection of 99mTc-DTPA, the time-activity curves recorded by a gamma camera over the liver and lung in a group of otherwise normal cigarette smokers decreased up to 30 min after injection, with time courses that could essentially be superimposed on each other; the curve recorded over the thigh with a separate scintillation probe continued to increase. The curve recorded over the cranium had a time course similar to that for the liver and lung. Following aerosol inhalation, the lung clearance rates over the initial 7 min when background subtraction was used, based on the liver, cranium, and thigh were, respectively, 4.9 +/- 2.9, 4.7 +/- 2. 6, and 5.4 +/- 3.4 (SD) %/min, compared with 4.1 +/- 2.2%/min without subtraction. The corresponding values based on 30 min of data were 3.3 +/- 1.4, 3.4 +/- 1.4, 4.2 +/- 2.3, and 2.8 +/- 1. 0%/min. When the liver was used for background, the lung clearance curves were clearly multiexponential, whereas thigh correction tended to give curves that were monoexponential or even convex upward on semilogarithmic axes. With an appropriate region for background, the true shape of a lung curve can be identified, which permits the study of an intervention on the clearance while it is in progress. The intravenous DTPA, required for calibrating the background regions, can be given before inhalation of the tracer.

Adolescent↗
PubMed1998

The use of nuclear medicine in infections.

The spectrum of infectious diseases has changed over the last few years, hence the requirements for radionuclide imaging for the detection of infection are becoming more demanding so that, although gallium-67 and labelled leucocytes remain useful agents, there is currently great interest in the development of new agents especially able to target chronic, non-pyogenic inflammation. Agents can be classified according to the site at which the radiolabel is targeted: pre-endothelial (for example, labelled leucocytes), endothelial (for example, labelled anti-endothelial monoclonal antibodies) or post-endothelial (for example, fluorine-18-fluorodeoxyglucose (FDG)). 67Ga and labelled polyclonal human immunoglobulin (HIG) localize at inflammation initially as a result of increased endothelial permeability, followed by retention of the label through binding to local extravascular receptors. Labelled leucocytes are avidly taken up by acute pyogenic inflammatory foci but perform less well in chronic inflammation. Other indications for labelled leucocytes include bone infection and undiagnosed fever. Nevertheless, since many causes of the latter do not stimulate a neutrophilic infiltrate, a non-specific agent, such as 67Ga, FDG or HIG, may be preferable, especially in patients with no immediate significant medical history. Since endothelial E-selectin expression is closely correlated to lymphocyte migration, labelled anti-E-selectin monoclonal antibody may also have a potential role for imaging chronic inflammation.

Biomarkers↗
PubMed1998

Fundamentals of tracer kinetics for radiologists.

With the increasing application of dynamic and functional techniques to radiological imaging modalities other than nuclear medicine, it is becoming increasingly important for radiologists to understand the principles of tracer kinetics and for functional and physiological aspects of imaging to be expanded in radiological training. Tracer, or indicator, kinetics can be broken down in six fundamental physiological variables (transit time, distribution volume, clearance, extraction fraction, blood flow and permeability-surface area product), three fundamental physical variables (time, mass and volume) and three fundamental equations (transit time equation, dilution equation and Fick equation). This teaching review defines the six fundamental physiological variables, discusses their relevance to functional imaging and describes how they may be measured using radiological techniques. It also illustrates how most of their tracer kinetics are based on one or other of the three fundamental equations.

Contrast Media↗
PubMed1997

Expression of vascular cell adhesion molecule-1 by vascular endothelial cells in immune and nonimmune inflammatory reactions in the skin.

Expression of VCAM-1 was compared with that of E-selectin in cytokine-induced lesions and in delayed-type hypersensitivity reactions to tuberculin purified protein derivative (PPD) in pig skin. Lumenally expressed Ags were quantified by measuring localization in skin of i.v. injected (111)In-mAb 10.2C7 (anti-vascular cell adhesion molecule-1 (anti-VCAM-1), (125)I-mAb 1.2B6 (anti-E-selectin), and (99m)Tc-MOPC21 (control IgG1). Anti-VCAM-1 mAb uptake was greater following intradermal (i.d.) injection of TNF-alpha than following injection of IL-1, while the two cytokines induced similar uptake of anti-E-selectin. In immunologically naive pigs there was no detectable increase in anti-VCAM-1 after i.d. injection of PPD, although anti-E-selectin uptake was increased at 3 and 6 h. In contrast, i.d. injection of PPD in sensitized pigs led to increased uptake of both anti-VCAM-1 and anti-E-selectin at 6, 8, 24, and 48 h, each of which was significantly greater than the uptake of control IgG1 into the same lesions (each p < 0.01). Anti-TNF-alpha mAb abolished the increased uptake of anti-VCAM-1 3 and 8 h following i.d. injection of PPD in sensitized pigs and significantly inhibited uptake at 24 h (p = 0.0025), but did not significantly reduce uptake of anti-E-selectin. We conclude that in this delayed-type hypersensitivity model 1) E-selectin expression by endothelial cells follows sequential Ag nonspecific and immune-specific phases, 2) increased VCAM-1 expression by endothelial cells is only seen in sensitized animals, and 3) expression of VCAM-1 appears to be relatively more dependent on TNF-alpha than E-selectin. Differential expression of E-selectin and VCAM-1 may influence the leukocytic infiltrate during the course of nonspecific and immune-specific inflammatory reactions.

Animals↗
PubMed1997

Endothelial activation in monosodium urate monohydrate crystal-induced inflammation: in vitro and in vivo studies on the roles of tumor necrosis factor alpha and interleukin-1.

OBJECTIVE: There is relatively little direct evidence for the roles of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) in activating endothelium in vivo. The aim of this study was to use in vitro and in vivo models to investigate the contribution of these cytokines to both E-selectin expression and the recruitment of polymorphonuclear cells (PMN) in monosodium urate monohydrate (MSU) crystal-induced inflammation. METHODS: MSU crystals were incubated with freshly isolated mononuclear cells, after which the harvested supernatants were tested for their ability to induce E-selectin expression during coculture with human umbilical vein endothelial cells. Subsequent experiments were performed with the addition of neutralizing anticytokine antibodies/antisera. The role of TNF alpha was then studied in an MSU crystal-induced monarthritis model, in the presence or absence of anti-TNF alpha (5 mg/kg intravenously). 99mtechnetium (99mTc)-labeled PMN cells and (111)indium (111In)-labeled anti-E-selectin monoclonal antibody (MAb) 1.2B6 were intravenously administered 4 hours after intraarticular injection to quantify PMN recruitment and E-selectin expression in inflamed joints. RESULTS: MSU crystals were a potent stimulus for IL-1 and TNF alpha production by monocytes in vitro, and these cytokines fully accounted for MSU crystal-stimulated, monocyte-mediated endothelial activation. In the MSU crystal-induced monarthritis model, TNF alpha blockade was very effective in suppressing both E-selectin expression and PMN emigration into the inflamed joints, as judged by gamma-camera image analysis and postmortem tissue counting following the intravenous injection of 99mTc-PMN and 111In-anti-E-selectin MAb. CONCLUSION: IL-1 and TNF alpha appear to be the only factors released by monocytes following incubation with MSU crystals, which induce E-selectin expression in vitro. Anti-TNF alpha is effective in suppressing endothelial activation and PMN recruitment in vivo E-selectin imaging can be used to assess the endothelial response to therapy and may prove useful for clinical studies.

Animals↗
PubMed1997

Indium-111 labelled lymphocytes: isotope distribution and cell division.

Since lymphocytes continue to proliferate and divide in vivo, it is important to determine the fate of a radionulide following lymphocyte labelling. Using the mixed lymphocyte reaction (MLR), we induced indium-111 labelled lymphocytes from a specific in-bred rat strain (AS) to divide and then observed the subsequent 111In distribution between cells and supernatant. L10 and L12.4 cells, which are allospecific CD4+ T lymphocytes from the AS rat, were stimulated in the MLR by antigen-presenting cells from the August rat, a different strain. We labelled L10 or L12.4 lymphocytes on day 0, the first day of the stimulation cycle, and continued to culture the lymphocytes in vitro. The proliferation of the cells was estimated according to their increase in number. The distribution of 111In between cell and supernatant fractions and between viable and dead (but intact) cells was measured in the cell suspension each day after labelling. The metabolic activity of 111In-labelled lymphocytes was compared with control cells by measuring their uptake of fluorine-18 fluorodeoxyglucose ([18F]FDG). 111In-labelled lymphocytes showed a poor proliferative response compared with control cells 24-48 h after labelling but increased in number after this time. From 24 to 72 h, about 70% of 111In was in the supernatant but only about 5%-10% was associated with intact dead cells. These dead cells tended to retain their 111In, losing less than 30% per day, suggesting that 111In in the supernatant was the result of active elimination from viable cells. Moreover, 24 h after culture, considerably more 111In was associated with viable than with dead lymphocytes, although over the next few days this distribution reversed. 111In-labelled lymphocytes took up more [18F]FDG than control cells at 24 h but not at 0 or 72-96 h; the maximum [18F]FDG uptake coincided with the greatest reduction in cell number. Furthermore, [18F]FDG uptake correlated with the initial 111In burden in lymphocytes labelled with 111In 24 h previously. The results are consistent with active elimination of 111In by 111In-labelled lymphocytes. The energy requirements for this are diverted away from cell division, thereby increasing the probability of cell death. As lymphocytes become 111In deplete, they recover their capacity to proliferate and their risk of death decreases. These findings have important implications for 111In-labelled lymphocyte scintigraphy, suggesting that cells remaining viable immediately after labelling will either subsequently die or alternatively eliminate the label.

Animals↗
PubMed1997

ECAT ART - a continuously rotating PET camera: performance characteristics, initial clinical studies, and installation considerations in a nuclear medicine department.

Advances in fully three-dimensional (3D) image reconstruction techniques have permitted the development of a commercial, rotating, partial ring, fully 3D positron emission tomographic (PET) scanner, the ECAT ART. The system has less than one-half the number of bismuth germanate detectors compared with a full ring scanner with the equivalent field of view, resulting in reduced capital cost. The performance characteristics, implications for installation in a nuclear medicine department, and clinical utility of the scanner are presented in this report. The sensitivity (20 cm diameterx20 cm long cylindrical phantom, no scatter correction) is 11400 cps.kBq-1.ml-1. This compares with 5800 and 40500 cps.kBq-1.ml-1 in 2D and 3D respectively for the equivalent full ring scanner (ECAT EXACT). With an energy window of 350-650 keV the maximum noise equivalent count (NEC) rate was 27 kcps at a radioactivity concentration of approximately 15 kBq.ml-1 in the cylinder. Spatial resolution is approximately 6 mm full width at half maximum on axis degrading to just under 8 mm at a distance of 20 cm off axis. Installation and use within the nuclear medicine department does not appreciably increase background levels of radiation on gamma cameras in adjacent rooms and the dose rate to an operator in the same room is 2 microSv. h-1 for a typical fluorine-18 fluorodeoxyglucose (18F-FDG) study with an initial injected activity of 370 MBq. The scanner has been used for clinical imaging with18F-FDG for neurological and oncological applications. Its novel use for imaging iron-52 transferrin for localising erythropoietic activity demonstrates its sensitivity and resolution advantages over a conventional dual-headed gamma camera. The ECAT ART provides a viable alternative to conventional full ring PET scanners without compromising the performance required for clinical PET imaging.

Equipment Design↗
PubMed1997

Pulmonary technetium-99m diethylene triamine penta-acetic acid aerosol clearance as an index of lung injury.

Although the clearance of an inhaled nebulised radioaerosol has long been employed as a measure of lung function, this test has not found favour in nuclear medicine units to the extent that might originally have been anticipated. In this review the theoretical basis of solute transfer is considered and the measurement of radioaerosol clearance discussed. Thereafter the various clinical applications of alveolar permeability measurement are outlined. Finally, possible reasons for the restricted clinical use of the diethylene triamine penta-acetic acid clearance technique are considered. It is concluded that the technique should provide a rapid screening evaluation of the HIV+ve patient presenting predominantly with chest symptoms.

Administration, Inhalation↗
PubMed1997

The ureteric jet index: a novel measure of divided renal function.

The aim of this study was to evaluate an index of divided renal function based on the quantification of the ureteric jets seen on colour Doppler ultrasound of the bladder. Thirty-one patients attending for scintigraphic renography underwent colour Doppler ultrasound with video recording for 5 min. Divided renal function was calculated as the proportion of jets from the right-sided orifice ('jet index'). This was compared with the corresponding 'scintigraphic index' found using Patlak-Rutland graphical analysis. Absolute discrepancies were calculated. Twenty-eight of thirty-one (90%) of studies were diagnostic for the calculation of jet indices. The mean jet index was 52% (n=28, SEM=5.8%) compared to a mean scintigraphic index of 54% (n = 28, SEM = 4.0%). The two scores were correlated, with a correlation coefficient of 0.72 and the median absolute difference between the two scores was 7.7%. Forty-three per cent (12/28) of subjects had discrepancies in the two scores of 5% or less. The score differences, however, showed a highly skewed distribution with 32% (9/28) subjects showing discrepancies over 20%. This discordant group (> 20% difference) included three patients with functional pelviureteric obstruction, one with a pelvic mass and one with an underfilled bladder. Two patients with very poor quality jets had impaired renal function. In one case, the index improved after angioplasty for renal artery stenosis. This simple test is a useful adjunct to urinary tract ultrasound but should be interpreted alongside evidence of renal obstruction, and complements rather than replaces existing tests.

Adolescent↗
PubMed1997

The role of prosody in the acquisition of grammatical morphemes: evidence from two Chinese languages.

This paper examines two issues concerning the acquisition of grammatical morphemes: (1) How is the acquisition of grammatical morphemes influenced by prosodic and phonological characteristics of the language being learned? and (2) What sorts of prosodic and phonological properties do grammatical morphemes have that might aid children in applying particular segmentation strategies? To address these issues, we compared the acquisition of grammatical morphemes in a pair of morphosyntactically similar but prosodically different languages, namely Taiwan Mandarin Chinese (TMC) and Taiwanese (TW). We analyse the patterns of realization and omission of a highly frequent subset of grammatical morphemes in six children's speech, recorded between the ages 1:6 and 2:3. The results from the between-language comparisons suggest that rhythmic characteristics of languages can affect segmentation by providing different kinds of prosodic handles for children to grasp at.

Child Language↗
PubMed1997

Comparative kinetics of microvascular inulin and 99mTc-labelled diethylenetriaminepenta-acetic acid exchange.

1. After simultaneous intravenous injection as a mixture, 99mTc-labelled diethylenetriaminepentaacetic acid (99mTc-DTPA; molecular mass 492 Da) and inulin (approximately 6000 Da) gave arterial plasma clearance curves consisting of three exponentials, the time courses of which were not significantly different between the two solutes. 2. The ratio of 99mTc-DTPA to inulin concentration in antecubital venous plasma (normalized to the ratio in arterial plasma at 30 s) was 0.6, significantly less than unity, within 2 min after intravenous injection, but increased to reach unity by 60 min. The minimum concentration ratio of 99mTc-DTPA to inulin in arterial plasma was 0.75 at 4 min, also rising to just above unity at 60 min. 3. The extraction fraction from plasma to interstitial space was higher for 99mTc-DTPA (approximately 0.5) than for inulin (approximately 0.2). For both solutes, the net extraction fraction decreased with time, becoming negative at about 25 min after injection. Thereafter, the net extraction fractions remained negative, between -0.05 and -0.1, and not significantly different between the two solutes. 4. 99mTc-DTPA time-activity curves recorded over the limbs with scintillation probes were biphasic, with an initial phase corresponding closely in time with the first exponential of the arterial 99mTc-DTPA plasma clearance curve. The second phase corresponded in time to the intermediate exponential of the arterial 99mTc-DTPA plasma clearance curve. 5. The time course of net 99mTcm-DTPA extraction fraction across the forearm vascular bed was bi-exponential, with phases corresponding in time with the two phases of the limb uptake curves. 6. Deconvolution analysis of the limb time-activity curves, using the arterial time-concentration curve as the input function, gave bi-exponential 99mTc-DTPA impulse response curves in which the time courses of the exponentials corresponded with the first and intermediate exponentials of the arterial 99mTc-DTPA clearance curve. 7. The bi-exponential nature of the equilibrium of 99mTc-DTPA between vascular and interstitial compartments suggests the presence of two separate functional volumes within the interstitial space. Although 99mTc-DTPA and inulin clearly diffuse at different rates across the endothelium, as would be expected from their disparate sizes, the similarity in the time courses of their initial exponentials and simultaneous equalization of transfer rates (i.e. when net extraction fraction was zero) is consistent with the hypothesis that inulin moves initially into a smaller functional interstitial fluid volume than 99mTc-DTPA. The total distribution volumes, however, are not significantly different between the two solutes.

Adult↗
PubMed1997

Ischaemia-reperfusion injury in the rat kidney: the effect of preconditioning.

OBJECTIVES: To design and establish a model to examine whether brief periods of renal artery occlusion (ischaemic preconditioning, IP) confers protection from the effects of a subsequent period of ischaemia and reperfusion of the rat kidney. MATERIALS AND METHODS: Ninety rats were randomized into six groups, i.e. sham-operated controls; IP alone; a 20 or 40 min period of left renal ischaemia (RI) alone; and IP followed by a 20 or 40 min period of RI. Preconditioning involved the sequential clamping of the left renal artery for 4 min and its release for 11 min, a total of four times, a 'critical interval' of 30 min before the ischaemic insult. Left renal tissue integrity was determined by dimercapto-succinic acid (DMSA) radionuclide imaging on a gamma-camera both immediately (day 0) and 2 and 9 days later. Acute tubular necrosis was also assessed histologically. RESULTS: RI for 20 min resulted in a significant decrease in left renal tissue integrity on day 2 only (P < 0.001), whereas RI for 40 min caused significant left renal dysfunction on day 0, day 2 and day 9 (P < or = 0.01). For a given duration of ischaemia, there was no significant difference between results from (IP + RI) rats compared with RI-only rats at any of the three times. There was no significant alteration in renal tissue integrity in the IP-only rats compared with sham-operated controls. Histological findings paralleled the data obtained from DMSA uptake. CONCLUSIONS: The IP regimen and 30 min 'critical interval' confers no protection to the kidney from a 20 or 40 min ischaemic episode. The IP regimen itself appears to have no effect, confirming the validity of our experimental model.

Animals↗
PubMed1997

A comparison between 111In-anti-E-selectin mAb and 99Tcm-labelled human non-specific immunoglobulin in radionuclide imaging of rheumatoid arthritis.

We have developed and validated a method for imaging inflammation using a monoclonal antibody (1.2B6) against E-selectin, an endothelial-cell specific adhesion molecule. This study was undertaken to compare 111In-1.2B6 with 99Tcm-labelled non-specific IgG (99Tcm-HIG) in the detection of synovitis in 11 patients with rheumatoid arthritis (RA). Imaging was performed 4 h and 20-24 h post-injection (pi) of 555 MBq 99Tcm-HIG and 15 MBq 111In-1.2B6. Scintigraphic results were compared with clinical scores of joint involvement. Joint uptake was semiquantitated. The scintigraphic appearances with both tracers correlated well, although 111In-1.2B6 at 24 h showed the highest detection rate. Taking joint tenderness or swelling as evidence of clinical activity, the sensitivity of 111In-1.2B6 at 4 h and 24 h was 69% and 82%, respectively, compared with 69% and 62% for 99Tcm-HIG. 111In-1.2B6 also displayed abnormal activity over a number of joints that appeared silent on clinical examination. Joint-to-soft tissue ratios were higher for 111In-1.2B6 at 24 h (4.0 +/- 1.9; p < 0.0001 vs all) than at 4 h (2.4 +/- 1.4) or than for 99Tcm-HIG at 4 h and 24 h (1.6 +/- 0.5 and 2.3 +/- 0.7, respectively). Net 111In counts over joints increased significantly between 4 h and 24 h (mean change: 54 +/- 40%). This study demonstrates that 111In-1.2B6 scintigraphy is a sensitive method by which to assess RA activity and that targeting is more intense and specific than using 99Tcm-HIG. However, the optimum time for 111In-1.2B6 scintigraphy is 24 h whereas good results are already obtained with 99Tc-HIG at 4 h pi. Current efforts are directed at developing 99Tcm-labelled 1.2B6 for imaging endothelial activation.

Aged↗
PubMed1997

Dissociation of neutrophil emigration and metabolic activity in lobar pneumonia and bronchiectasis.

In animal models of pulmonary inflammation, neutrophils exhibit a dramatic influx of glucose in periods of high metabolic activity. This information was utilized to develop a technique, involving positron emission tomography (PET) of 2-[18F]-fluoro-2-deoxy-D-glucose (18FDG), which measures neutrophil activity in situ. This technique was applied in a comparative study of neutrophil function in patients with acute lobar pneumonia or bronchiectasis. Neutrophil emigration was measured by gamma-scintigraphy of intravenously injected 111In-labelled granulocytes and neutrophil activity determined by PET of 18FDG. Neutrophil emigration was evident in 4 out of 5 bronchiectasis patients, whilst no emigration was apparent in the two pneumonia patients studied, consistent with animal studies showing maximum emigration soon after challenge. In contrast, 18FDG uptake was markedly increased in 4 out of 5 pneumonia patients but not in the patients with bronchiectasis. Localization of radioactivity to neutrophils was confirmed by microautoradiography of lavage fluid in a patient with pneumonia. These results suggest that the elevated uptake of glucose by neutrophils during the inflammatory response is a postmigratory event, most likely reflecting the respiratory burst, and that high levels of neutrophil emigration are not necessarily associated with significantly increased metabolic activity of these cells.

Adult↗