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Biomedical subjects

A M Peters

Publications and source records attributed to A M Peters.

At least 127 records · Page 7Linked to original sources
PubMed1994

Oxygen and 99mTc-MAA shunt estimations in patients with pulmonary arteriovenous malformations: effects of changes in posture and lung volume.

BACKGROUND: Patients with arteriovenous malformations are routinely monitored with arterial oxygen saturation (SaO2) estimations (breathing air) from which an oxygen shunt fraction can be calculated. This simple estimation has been compared with an anatomically defined estimate of the right to left shunt using a radioisotopic method. The fall in SaO2 which occurs in patients with pulmonary arteriovenous malformations in the erect posture and at high lung volumes was used to test the ability of SaO2 alone to follow changes in right to left shunt. METHODS: Radiolabelled albumin macroaggregates (99mTc-MAA) or microspheres (MS) were injected intravenously and kidneys and lungs were imaged. The shunt fraction (QS/QTTc) in the supine position at functional residual capacity (baseline) was obtained by quantifying right kidney radioactivity. On standing or while breath holding at total lung capacity, shunt fraction was calculated from baseline QS/QTTc and from lung counts and the injected dose. Arterial oxygen saturation (SaO2) was recorded by a pulse oximeter for calculation of the oxygen shunt (QS/QTO2) (breathing air). RESULTS: In the postural study (n = 8) SaO2 decreased from a mean (SD) value of 89 (5)% supine to 80 (6)% erect, corresponding to QS/QTO2 28 (8)% and 44 (8)% respectively. QS/QTTc increased from 28.7 (10.3)% to 39 (14.3)%. In the lung volume study (n = 8) QS/QTTc increased from 16.6 (11.5)% at functional residual capacity to 23.3 (11.9)% at total lung capacity while QS/QTO2 increased from 19.5 (7.5)% to 25.9 (10.6)% respectively. When all measurements were compared for QS/QTTc% and QS/QTO2% (n = 32) the difference in the mean values was 2.5% (absolute) and the limits of agreement between the two methods were +38% to -18% (relative). In neither the postural nor the volume study did delta (QS/QTO2) reliably predict delta (QS/QTTc)%. CONCLUSIONS: In pulmonary arteriovenous malformations the simple physiological shunt calculated from SaO2 breathing air agreed well with the anatomical right to left shunt measured with 99mTc-MAA, but predicted poorly the changes in anatomical shunt induced by postural or lung volume changes.

Adult↗
PubMed1994

Characterization of E-selectin expression in vivo with use of a radiolabeled monoclonal antibody.

We have studied endothelial luminal surface expression of E-selectin in vivo in the pig. Intravenous interleukin-1 (IL-1, 5-micrograms/kg bolus +/- 50-ng.kg-1 x min-1 infusion for 2 h) induced E-selectin expression in many organs, as shown by immunostaining and selective clearance of intravenous 111In- or 99mTc-labeled anti-E-selectin monoclonal antibody (MAb 1.2B6) compared with radiolabeled immunoglobulin G1 control. Specific clearance of MAb 1.2B6 commenced 30-45 min after intravenous IL-1. Skin sites injected with IL-1, tumor necrosis factor, phytohemagglutinin, or phorbol myristate acetate at various times (45 min-24 h) before exsanguination showed specific accumulation of MAb 1.2B6 when 99mTc-MAb 1.2B6 and 111In-control immunoglobulin G1 were injected intravenously 10 min before exsanguination. This was maximal in 2-h IL-1 and tumor necrosis factor lesions and after 9 h in phytohemagglutinin and phorbol myristate acetate lesions. This novel approach has allowed us to quantify changes in vascular luminal expression of E-selectin in models of inflammation involving systemic and localized endothelial cell activation and has considerable potential for analyzing these changes in relation to leukocyte traffic and other manifestations of inflammatory responses in vivo.

Animals↗
PubMed1994

What is the nephrogram?

One of the oldest questions in radiology, "what is the nephrogram?", has been approached in a novel manner using dynamic bolus contrast enhanced computed tomography to monitor the arrival and distribution of contrast agent in the normal kidney. A modification of a mathematical technique first developed for applications in positron emission tomography has been used to analyse the data. It is concluded that the blood pool contribution to the nephrogram is greater in the first minutes after rapid bolus contrast injection than generally supposed and that the "immediate" nephrogram is a predominantly blood pool contrast phenomenon.

Aorta, Abdominal↗
PubMed1994

Development of radiolabelled white cell scanning.

The use of gamma emitting radioisotope labelled white cells for imaging inflammation was introduced in 1976. It was possible to study the whole body distribution of granulocytes using this method. Cells were labelled in plasma using tropolone as chelate to avoid cell activation which causes non-physiological persistent lung uptake. Such studies revealed labelled cell uptake in bone marrow, liver and spleen in normal subjects. Intense liver activity was found in cases of cell damage resulting in cell destruction by the liver. The large splenic pool of leucocytes could be mobilized rapidly to sites of inflammation and indeed the fall in splenic activity was a measure of the degree of inflammation. Measurements of the faecal excretion of 111In-labelled granulocytes were also used to assess Crohn's disease activity. Alternatively, the whole body retention of 111In was used. Later studies have involved the use of 99mTc, initially using labelled colloids, which resulted in cell activation and later using the lipophilic complex HMPAO to label leucocytes. The several advantages over 111In for imaging inflamed bowel are described. Early imaging is important to avoid non-specific bowel activity. Newer approaches include labelling immunoglobulins, monoclonal granulocyte antibodies and targeting of activated endothelium adhesion molecules. Such techniques remain experimental and the best current technique for localizing inflammation is to use radiolabelled leucocytes.

Antibodies, Monoclonal↗
PubMed1994

Imaging vascular endothelial activation: an approach using radiolabeled monoclonal antibodies against the endothelial cell adhesion molecule E-selectin.

UNLABELLED: E-selectin is an endothelial cell-specific adhesion molecule for leukocytes expressed on the luminal surface of vascular endothelium during inflammatory responses. Because E-selectin expression is dependent upon ongoing stimulation by cytokines, this molecule offers a potentially useful target for imaging tissues in disease states involving cytokine-mediated endothelial cell activation. METHOD: To assess the imaging potential of an anti-E-selectin monoclonal antibody (Mab) 1.2B6, the accumulation of intravenously injected 111In-labeled Mab 1.2B6 was compared to that of 111In-control antibody in a model of arthritis in the pig. Injection of phytohaemagglutinin (PHA) into a knee led to E-selectin expression on vessels in the synovium and draining deep inguinal lymph nodes, as demonstrated by immunohistology. No E-selectin expression was seen in the control knee injected with buffer alone. Animals were given 111In-Mab 1.2B6 or 111In-control antibody intravenously 3 hr after the intra-articular injection of PHA. Radiolabeled antibody uptake was measured by direct counting of tissues 25 hr postmortem. RESULTS: The accumulation of radiolabeled control IgG in synovium and draining deep inguinal lymph nodes of PHA-injected knees was significantly higher than accumulation in tissues injected with buffer alone; however, the comparable ratios in animals receiving radiolabeled Mab 1.2B6 were significantly greater. Scintigraphy performed 24 hr after 111In-Mab 1.2B6 injection showed obvious localization of activity in the inflamed knee in each of three animals. CONCLUSION: Radiolabeled anti-E-selectin Mab can be used to image localized inflammatory tissues. This approach may be useful for investigating activated endothelium in human disease.

Animals↗
PubMed1994

Normalization of glomerular filtration rate in children: body surface area, body weight or extracellular fluid volume?

UNLABELLED: Glomerular filtration rate (GFR) is usually expressed in relation to body surface area (BSA) for standardization and comparison between individuals of different sizes, although relating it to extracellular fluid volume (ECV) is technically much simpler because the ratio GFR/ECV is almost equal to the rate constant of the second exponential of the 51Cr-EDTA plasma clearance curve. The aim of this study was to investigate the physiological validity of expressing GFR in relation to ECV by comparing it with GFR normalized for BSA and body weight. METHODS: GFR was measured from a five-sample 51Cr-EDTA plasma clearance curve. After appropriate scaling, the rate constant of the terminal exponential is equal to GFR/ECV. RESULTS: GFR normalized by any of the three variables increased between 0-6 mo, but was less in the case of GFR/weight compared with the other two. From 6 to 24 mo, GFR/BSA continued to increase, whereas GFR/ECV and, in particular, GFR/weight remained relatively constant. It appears that as the child grows to age 6 mo, weight outstrips BSA and ECV but is followed by GFR. From 6 to 24 mo, weight, ECV and GFR increase at a faster rate than BSA. By applying regression analysis to the curves of GFR and its normalization variables versus age, expected (e) and relative (r, i.e., observed/expected) values were obtained for each patient. In the age group 6-24 mo, but not 0-6 mo, r[GFR/ECV] was significantly closer to e[GFR/ECV] than the corresponding comparisons with r and e[GFR/BSA] (p < 0.001) and r and e[GFR/weight] (p < 0.002), supporting the hypothesis that as ECV deviates from the expected value for the patient's age, it tends to be followed by GFR. CONCLUSION: Our data show that ECV is the optimal normalization variable in children, particularly those over the age of 6 mo.

Aging↗
PubMed1994

Localization of metastatic gastroenteropancreatic tumours by somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]-octreotide.

Most gastroenteropancreatic tumours express somatostatin receptors, allowing imaging using radiolabelled somatostatin analogues. Octreotide can be modified by coupling a DTPA moiety to the N-terminal D-phenylalanine to allow labelling with In111. We studied the comparative effectiveness of this radiopharmaceutical in identifying tumour extent. Twenty-two patients with metastatic gastroenteropancreatic tumours were scanned using [111In-DTPA-D-Phe1]-octreotide. In 11 patients with the carcinoid syndrome, one of six primary lesions was identified by CT scanning and by [111In-DTPA-D-Phe1]-octreotide scanning. Hepatic metastases were present in all patients, 9 of whom had positive scintigraphy. Two other sites of intra-abdominal uptake and four distant sites, not previously identified, were demonstrated. Five other distant sites were confirmed to be carcinoid metastases. All 11 patients with other gastroenteropancreatic tumours had positive scans, demonstrating 7/9 primary lesions, 12 intra-abdominal lesions, including hepatic metastases in all cases, and one distant lesion, all previously identified. Thus [111In-DTPA-D-Phe1]-octreotide imaging effectively identified the extent of metastatic disease from gastroenteropancreatic tumours, and confirmed lesions whose significance was uncertain following previous imaging procedures.

Adult↗
PubMed1993

Splenic uptake of immune complexes in man is complement-dependent.

We have examined the effects of hereditary homozygous C2 deficiency on the processing of radiolabeled soluble immune complexes (IC). A patient with C2 deficiency was studied before and after treatment with fresh frozen plasma (FFP). Hepatitis B surface Ag (HBsAg):anti-HBsAg immune complexes were prepared in vitro using Ag radiolabeled with 123I, and injected intravenously. Dynamic and static gamma-scintigraphy was performed to delineate the sites and kinetics of complex clearance. The patient was initially studied when her C2 level and CH50 were zero, and again 1 wk later after treatment with 12 units of FFP, which normalized these parameters. Before treatment there was rapid uptake of complexes by the liver (t90% [time for 90% uptake] = 13.6 min) and rapid clearance from the circulation (t1/2 = 6.8 min). No splenic uptake was detected, and there was no binding of complexes to erythrocyte CR1. Between 30 and 60 min there was release of 11% of the tracer from the liver. In the second study, performed after normalization of classical pathway complement activity, the t1/2 of IC clearance increased to 9.8 min, and t90% was 27 min. Twenty percent of injected complexes now localized to the spleen, and there was no longer any release of complexes between 30 and 60 min. The kinetics of IC processing and the sites of uptake in this posttherapy study were closely similar to two normal subjects studied in parallel, with a maximum of 72% of injected complexes binding to erythrocytes. These observations indicate that the uptake of immune complexes in the spleen in humans is complement-dependent, and suggest that the observed predisposition to SLE in patients with complement deficiency may be related to abnormal processing of immune complexes.

Antigen-Antibody Complex↗
PubMed1993

Improvement of superoxide production in monocytes from patients with chronic granulomatous disease by recombinant cytokines.

Cytokines have been shown to modulate the respiratory burst of polymorphonuclear leukocytes and monocytes from normal controls. We have examined whether monocytes from children with chronic granulomatous disease (CGD) can be primed by cytokines other than interferon-gamma (IFN gamma), which has been demonstrated to improve the production of reactive oxygen species in vivo and in vitro. Monocytes isolated from peripheral blood were cultured without and with IFN gamma (500 U/mL), tumor necrosis factor-alpha (500 U/mL), interleukin-1 beta (IL-1 beta) (100 U/mL), and IL-3 (100 U/mL). After 3 days of culture, the phorbolmyristate acetate (2 ng/mL) and the formyl-methionyl-leucyl-phenylalanine (0.1 mumol/L)-stimulated superoxide-production was determined in a microtiter system. In nearly all of the 14 patients examined (5 autosomal, 5 X-chromosomal, and 4 of unknown inheritance), an improvement of superoxide production could be demonstrated. The most impressive effect with the cytokines newly tested was seen with monocytes from autosomal CGD patients treated with IL-3 and stimulated by phorbolmyristate acetate. In single patients cultivation of monocytes with IL-6 and granulocyte-macrophage colony-stimulating factor resulted in only slight improvement of superoxide production. Our findings indicate that cytokines other than IFN gamma can positively modulate the defective respiratory burst in CGD and that each patient reacts with an individual pattern to different cytokines.

Cells, Cultured↗
PubMed1993

Amino acid infusion blocks renal tubular uptake of an indium-labelled somatostatin analogue.

The Indium-labelled somatostatin analogue pentetreotide has been successfully developed for imaging of somatostatin receptor positive tumours. However there is significant renal tubular uptake of the radiolabelled peptide, which can obscure upper abdominal tumours and would preclude its use for targeted radiotherapy. The aim of this study was to determine whether amino acid infusion, which has been shown to block renal tubular peptide reabsorption, diminishes renal parenchymal uptake of this radiolabelled analogue. Eight patients being scanned with the 111In-labelled somatostatin analogue, pentetreotide, for localisation of gastroenteropancreatic tumours received an infusion of synthetic amino acids. The ratio of isotope uptake in kidney to that in spleen was assessed, and compared to the ratio for matched control patients, to determine if amino acid infusion reduced renal parenchymal uptake of the radiopharmaceutical. The amount of isotope in the urine was determined to ensure that any effect of the amino acid infusion was unrelated to changes in clearance. Infusion of amino acids significantly reduced renal parenchymal uptake of isotope at 4 h. There was a non-significant increase in urinary clearance of isotope over the 4 h, consistent with reduced reuptake and a lack of effect on glomerular filtration rate. This technique, by preventing renal damage, may allow the use of this somatostatin analogue for local radiotherapy, and could be of wider value in blocking tubular re-uptake of potentially nephrotoxic agents, such as radiolabelled Fab fragments.

Adult↗
PubMed1993

Cardiopulmonary response to exercise in patients with intrapulmonary vascular shunts.

The majority of patients with intrapulmonary right-to-left shunting due to pulmonary arteriovenous malformations-exhibit good maximum exercise capacity (> 70% predicted) despite profound arterial oxygen desaturation. We studied seven such patients to assess tissue oxygen delivery during steady-state exercise. From rest to exercise [50 +/- 7 (SE) W] arterial saturation fell from 80 +/- 3 to 74 +/- 3%, and mean right-to-left shunt increased slightly from 31 +/- 4 to 34 +/- 5% (P = NS). Minute ventilation was high for oxygen uptake, and the ventilatory equivalent was raised (174 +/- 19% predicted) and was correlated with shunt size (r = 0.93). The majority of the patients maintained pulmonary alveolar blood flow within the predicted range for their power output, but total cardiac output was increased to 142 +/- 11% predicted due to flow through the shunt. Consequently, on exercise, oxygen delivery per unit oxygen consumption [2.3-3.3 (normal range 1.6-2.4)] and calculated mixed venous oxygen tension (27.0 +/- 0.8 Torr) were preserved. Arterial PCO2 rose on exercise by 2.8 +/- 1.2 Torr, in proportion to the ratio of flow through the shunt to total cardiac output (r = 0.73), but remained low (33.1 +/- 1.4 Torr) in absolute terms. The high cardiac output on exercise may be facilitated by a low pulmonary vascular resistance (0.33 +/- 0.08 mmHg.1-1.min, measured at rest), which may explain why exercise performance is better in these patients than in patients with equivalent hypoxemia from other causes.

Adolescent↗
PubMed1993

Reduced secretion of interleukin-1 and tumor necrosis factor-alpha by neonatal monocytes.

Monocytes were isolated from peripheral blood of preterm and term newborn infants and adult controls, and their capacity to secrete the inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) was investigated. Lipopolysaccharide (LPS)-stimulated neonatal monocytes secreted significantly less IL-1 (median: 1.1 U/ml) than monocytes from adult controls (median: 7.3 U/ml). In addition TNF-alpha production by LPS-stimulated neonatal monocytes (median: 610 pg/ml) was significantly lower when compared with controls (median: 2230 pg/ml). Our data provide evidence that neonatal monocytes have a profoundly impaired cytokine secretion.

Adult↗
PubMed1993

Functional imaging in computed tomography. The use of contrast-enhanced computed tomography for the study of renal function and physiology.

RATIONALE AND OBJECTIVES: Computed tomography (CT) numbers may provide the raw material for calculations of important physiologic parameters, such as organ regional perfusion and glomerular filtration rate. Because, except in cases of severe renal dysfunction, iodinated intravascular contrast agents are excreted primarily by passive glomerular filtration, the decline in their concentration in blood or tissues will reflect renal function. The time evolution of contrast agent distribution within the kidney, from blood to tubules, can also be seen as a measure of renal function. The authors illustrate how CT numbers may be employed to obtain useful data regarding renal function. METHODS: Two CT methods were used to yield information on renal function. Delayed CT: 2 hours after administration of 200 mL of a contrast agent (iohexol) for a routine CT, a patient with normal renal function was brought back to the scanner, and a single fixed section through the abdomen, including the psoas muscles, was imaged; the scan was repeated at 2, 3, and 4 hours. Large regions of interest were selected in soft tissue, and six measurements of CT numbers were taken and averaged for each time; after taking logs, these were plotted against time. Dynamic CT: A rapid bolus of 40 mL nonionic contrast agent was injected into an antecubital vein at 5 mL/sec. At a fixed level, images were taken through the center of the kidneys at 5-second intervals for 2 minutes after injection. The patient was allowed to breathe gently throughout the examination. Regions of interest were selected over the kidney and the aorta, and curves of CT numbers against time were generated; a Patlak plot was performed using the parameters measured. Using the renal CT numbers collected during the first 2 minutes after injection, it was possible to analyze the handling of the contrast agent and to obtain a measure of the glomerular filtration rate. RESULTS: Delayed CT: Data yielded good values for glomerular filtration rate; the typical patient illustrated had a glomerular filtration rate per unit extracellular fluid volume of 0.005 min-1. Dynamic CT: The correlation coefficient for the line fit was 0.97, a value typically found in these studies, indicating the efficacy and ruggedness of this method in spite of the patient's shallow breathing throughout the examination. CONCLUSIONS: Computed tomography offers the potential for quantitative and physiologic measurement that has not been widely explored. The problem with the delayed CT technique is that since measurements are made at 2 hours and onward, it is applicable only to patients who have received larger doses of contrast. Otherwise, the CT numbers are low and the measurement error, large. Also, bringing the patient back to the scanner 2 hours later may be inconvenient to both patient and radiologist, and may disrupt case scheduling. This method is, however, less inconvenient than the established blood-level measurement. The dynamic CT method yields a new measure of renal clearance, namely, clearance per unit volume of kidney. The disadvantages of this method are the radiation burden involved in repeated rapid CT scans and the fact that, if renal disease is uneven, a nonrepresentative slice could be chosen. Its advantages are its simplicity and that it can be completed within the first 2 minutes of a CT examination. It may be expected to have an interesting application to situations in which there is known renal disease. Although difficulties are associated with both of these techniques that could prevent their general adoption as clinical routines, they nevertheless should find application in selected patients and should prove useful research tools in the study of renal disease.

Contrast Media↗
PubMed1992

Granulocyte margination in the human lung and its response to strenuous exercise.

1. It is widely believed that the lung is an important site of granulocyte margination and releases most of the granulocytes of the peripheral neutrophilia of exercise. 2. We measured granulocyte margination in the lung in terms of the lung total blood granulocyte pool and the lung circulating granulocyte pool in eight patients without inflammatory disease or evidence of lung pathology by comparing the regional gamma-camera lung count rate of 111In-labelled granulocytes with that of 111In-labelled erythrocytes. According to the respective 111In activities in peripheral blood samples taken between 5 and 40 min after granulocyte injection, the lung marginating granulocyte pool was 0.78 (SEM 0.045) of the lung total blood granulocyte pool or 4.6 (0.92) of the lung circulating granulocyte pool 5 min after injection, decreasing to plateau values of 0.57 (0.053) and 1.53 (0.28) from 20 min after injection. This compared with corresponding whole-body ratios of about 0.6 and 1.5, respectively. 3. After 4 min of maximal exercise in four normal subjects given 111In-labelled granulocytes 60 min before exercise, the 111In-labelled granulocyte count rate over the lung increased to 1.23 (0.05) of the pre-exercise value with a time course that was essentially identical with the time course of the peripheral native neutrophilia. The spleen 111In signal decreased with the same time course, reaching a minimum of 0.63 (0.05) of the pre-exercise level at 5-10 min after the end of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗