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Biomedical subjects

A M Peters

Publications and source records attributed to A M Peters.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Intrasplenic blood cell kinetics in man before and after brief maximal exercise.

1. After a 4 min period of maximal exercise in 10 normal subjects (14 studies), there was a consistent decrease in total blood volume and a consistent increase in erythrocyte indices, which were maximal immediately after exercise. Peripheral platelet and leucocyte counts increased, but did not reach maximal values until 5-10 min after the end of exercise. 2. The distributions of 99mTc-labelled erythrocytes (five studies), 111In-labelled platelets (five studies) and 111In-labelled granulocytes (four studies) were monitored with a gamma-camera immediately after injection and before and after maximal exercise performed 60 min after injection. 3. Labelled erythrocytes equilibrated rapidly between the spleen and circulating blood after injection, whereas labelled platelets and granulocytes equilibrated more slowly. After exercise, each cell type was released from the spleen with a time course that was the reciprocal of the time course of the corresponding cell count in peripheral blood. Thus, whereas the radioactivity of 99mTc-labelled erythrocytes in the spleen, which fell to 0.46 (SD 0.09) of the pre-exercise value, increased towards its baseline value as soon as exercise was completed, the radioactivities of 111In-labelled platelets and 111In-labelled granulocytes decreased, to respective minimum values of 0.61 (0.09) and 0.63 (0.09) of the pre-exercise levels, 5-10 min after the end of exercise. The exercise-induced changes in lung radioactivity for each cell type, and their time courses, broadly reflected those in the corresponding cell counts in peripheral blood. Liver radioactivity tended to decrease for each cell type.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Non-invasive techniques for the measurement of extraction fraction and permeability surface area product of 99Tcm DTPA in the human forearm.

Only a very limited number of clinical studies have been reported on the measurement of endothelial permeability to hydrophilic solutes (molecular weight less than 6000 Daltons) that normally gain free access to the extravascular space. Because of high extraction efficiencies into the extravascular space, the transfer rates of small solutes of molecular weight about 500 Daltons, like 99Tcm DTPA, are perfusion-dependent as well as diffusion-dependent. We describe non-invasive techniques for measurement of clearance and extraction fraction of 99Tcm DTPA into the extravascular space of the resting forearm using a scintillation probe, from which we then calculated permeability surface area (PS) product. Our values for extraction fraction of about 0.5 and for PS product of about 3 ml per minute per 100 ml tissue are comparable to the values reported in the literature for resting skeletal muscle using more invasive techniques.

Capillary Permeability↗
PubMed1992

Expressing glomerular filtration rate in terms of extracellular fluid volume.

Glomerular filtration rate (GFR) is routinely calculated from the second exponential of the bi-exponential plasma clearance of filtration markers such as Cr-51 EDTA and Tc-99m DTPA. By ignoring the first exponential, true GFR is overestimated, an error which increases with increasing GFR. The rate constant, lambda 2, of the second exponential represents the rate at which glomerular filtration 'turns over' the extracellular fluid (ECF) and so closely approximates GFR/ECF volume. Again, the error in the estimation of this ratio increases with increasing GFR, although in this case it underestimates the true ratio. Expressing GFR in terms of ECF volume, rather than in terms of body surface area, offers considerable technical and physiological advantages. The relationship between GFR/ECF volume and lambda 2, over a wide range of renal function, expressed as a second order polynomial, was GFR/ECF volume = -0.093 + 1.06 lambda 2 + 0.009 lambda 2(2) ml.min-1.l-1. The corresponding relationship between 'true' GFR (C1) and approximate GFR (i.e. based only on the second exponential--C2) was C1 = -0.58 + 1.012C2 -0.0011 C2(2) ml.min-1 For any level of renal function, the error in GFR/ECF volume, expressed as lambda 2, is less than the error in GFR expressed as C2. Since GFR may change as a direct result of a change in ECF volume, it is physiologically more relevant, and technically very much easier, to express GFR in terms of ECF volume rather than body surface area.

Adult↗
PubMed1992

Pulmonary granulocyte margination is increased in patients with inflammatory bowel disease.

The pulmonary granulocyte content of the lung was quantified in patients with inflammatory bowel disease (IBD) after injection of 111In-labelled granulocytes and compared with patient controls, who, on the basis of their negative white cell scans, were not considered to have active inflammation. The mean ratios of lung:liver count rates per pixel on the posterior gamma camera image in patient controls was 0.34 (S.D. 0.16, n = 8) at 1-1.5 h after injection of the cells, and 0.29 (S.D. 0.14, n = 18) at 2-4 h. This ratio was higher in patients with active IBD at both imaging times: 0.45 (0.13, n = 13, P > 0.05) and 0.44 (0.1, n = 19, P < 0.001). Patients with inactive IBD also had increased ratios at both imaging times: 0.6 (0.14, n = 7, P < 0.01) and 0.54 (0.15, n = 12, P < 0.001), respectively. In a further group of 12 patients with active IBD, there was no correlation between the lung:liver ratio and the severity of the IBD as assessed by whole-body 111In retention at 4-6 days after labelled cell injection. These patients were treated for 3 weeks with an oral, non-absorbable corticosteroid, after which there was a significant decrease in disease activity but no significant change in the lung:liver ratio. Inflammatory bowel disease appears to be associated with abnormal pulmonary granulocyte accumulation. It is not apparently related to disease activity but may be the result of an associated pulmonary abnormality.

Adhesiveness↗
PubMed1992

Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations.

BACKGROUND: Current treatment of patients with pulmonary arteriovenous malformations requires serial embolisations by means of steel coils or balloons. Measurement of right to left shunt is the most specific index of response to treatment. A new method of measuring shunt has been developed that is less invasive than traditional methods. METHODS: Right to left pulmonary shunt (expressed as percentage of cardiac output) was measured at rest in 19 patients with pulmonary arteriovenous malformations and six normal subjects by using intravenously injected albumin microspheres labelled with technetium-99m. The technique was compared with a simultaneous shunt measurement in subjects breathing 100% oxygen while they rested. The microsphere technique was adapted to measure the right to left shunt during exercise in 12 patients and five normal subjects with a new method of quantification. RESULTS: The mean (SD) shunt at rest as measured by the microsphere method was 23.2% (15.6%) in the patients and 2.7% (1.2%) in the normal subjects. When these values were compared with those of the 100% oxygen method the difference in mean values was 1% and the limits of agreement between the two methods -32% to +45%. The microsphere method is less invasive (arterial blood gas sampling is not required), quicker, and more comfortable for patients than the 100% oxygen method. In five of the normal subjects the mean (SD) 99mTc microsphere shunt increased from 2.9% (1.3%) at rest to 5.1% (2.9%) during exercise. In the 12 patients studied during exercise the shunt increased from 33.7% (12.7%) at rest to 41.7% (13.3%) during exercise in eight but decreased from 22.6% (2.4%) at rest to 17.6% (2.2%) during exercise in four. Arterial desaturation during exercise correlated with change in the size of the right to left shunt during exercise (r = +0.80). CONCLUSIONS: The microsphere method allows measurement of right to left shunt at rest and during exercise. Serial measurements at rest provide a simple, safe assessment of the physiological response to embolisation in patients with pulmonary arteriovenous malformations.

Adolescent↗
PubMed1992

Disturbance in renal haemodynamics and physiology in bone marrow transplant recipients treated with ciclosporin A.

The vascular disturbance associated with ciclosporin (CS) nephrotoxicity is poorly defined in both the normal and transplanted human kidney. Six bone marrow transplant recipients were studied before, during and after administration of CS. By analysis of time activity curves and clearance of Tc-99m DTPA, renal blood flow (RBF), filtration fraction (FF) and GFR were shown to fall on CS (GFR: p less than 0.001; RBF, FF: p less than 0.01). These haemodynamic variables did not fully recover with dose reduction or after discontinuation of therapy. Plasma renin activity (PRA) aldosterone and atrial natriuretic peptide did not change although there appeared a tendency for PRA to fall on CS. There was a reversible normokalemic metabolic acidosis. CS levels stayed within the therapeutic range. The partial reversibility of GFR, RBF and FF is consistent with CS-induced functional disturbance and reflects sensitivity to microvascular and tubular injury of the normal human kidney.

Adolescent↗
PubMed1992

Inhaled platelet-activating factor causes pulmonary neutrophil sequestration in normal humans.

Inhaled platelet-activating factor (PAF) causes bronchoconstriction and transient peripheral neutropenia in humans. We studied eight normal subjects to investigate whether inhaled PAF caused pulmonary neutrophil sequestration. All subjects received autologous 99mTc-red cells as a blood pool marker, seven received 111In-neutrophils, and one received 111In-platelets. Six subjects inhaled 48 micrograms of PAF. There was immediate pulmonary sequestration of 111In-neutrophils, maximal (218% baseline) at 6 min (p less than 0.001), returning to normal by 3 h. There was no change in circulating platelet count or pulmonary 111In-platelet transit. Methacholine inhalation caused equivalent bronchoconstriction to PAF, but it had no effect on neutrophil count or pulmonary 111In-neutrophil activity. We have demonstrated pulmonary neutrophil, but not platelet, sequestration after PAF. This supports a role for PAF as an inflammatory mediator in humans. This may be a useful model for exploring pulmonary neutrophil kinetics and preinflammatory processes.

Administration, Inhalation↗
PubMed1992

Immune complex processing in patients with systemic lupus erythematosus. In vivo imaging and clearance studies.

Abnormal processing of immune complexes (IC) may be important in the pathogenesis of systemic lupus erythematosus (SLE). The clearance of large soluble IC (comprising hepatitis B surface antigen (HBsAg)/anti-HBsAg) radiolabeled with 123I was examined in 12 normal subjects and 10 patients with SLE. IC localization was analyzed by static and dynamic gamma-scintigraphy. Initial IC clearance from blood was more rapid in patients (median t1/2 = 2.15 min) than normals (median t1/2 = 5.15 min) due to more rapid uptake in the liver. However, in the SLE group, up to 12% of complexes were released from the liver after 30-50 min. Splenic uptake of immune complexes was reduced in the patients and there was reduced ability to retain IC in this organ. Plasma complement levels and erythrocyte complement receptor type 1 numbers were reduced in the patients, resulting in defective opsonization of IC and reduced red cell binding in vivo. These observations support the hypothesis that IC handling is abnormal in SLE.

Adult↗
PubMed1992

Impaired left lower lobe ventilation in patients with cardiomegaly. An isotope study of mechanisms.

Reduced left lower lobe ventilation (V) in patients with enlarged hearts has been commonly observed on routine isotope ventilation-perfusion lung scanning, and there is evidence to show that this reduction is dependent on posture. Clinically, it may have a role in posture-dependent dyspnea and postoperative left lower lobe changes in cardiomegaly. Previous studies have shown improvement in left lower lobe V in the prone compared with the supine position. In 11 patients showing this phenomenon in krypton 81m V scanning, a mean relative reduction in V of 53 percent occurred at the left base. No significant change in perfusion or in the signal from preinjected technetium 99m macroaggregated albumin was observed between the two positions. No significant change in ventilatory turnover (measured with intravenous xenon 133) was seen either, suggesting that no air trapping takes place. By combining the data from the intravenous 133Xe (which gives the ratio, V/lung volume) and continuously inhaled 81mKr (which reflects regional V), an index of relative volume between the two sides was derived and shown to be significantly reduced at the left base on moving from the prone to supine positions (a mean reduction of 40 percent; p less than 0.02 by Wilcoxon signed rank test). Thus, the mechanism of postural left lower lobe hypoventilation in cardiomegaly is predominantly a regional loss of alveolar volume.

Cardiomegaly↗
PubMed1992

Platelet imaging of thromboembolism. Natural history of postoperative deep venous thrombosis and pulmonary embolism illustrated using the 111In-labelled platelet-specific monoclonal antibody, P256.

BACKGROUND: Deep venous thrombosis (DVT) and pulmonary thromboembolic disease are difficult to diagnose, particularly following surgery. This report demonstrates the use of 111In-labelled platelet-specific monoclonal antibody, P256 Fab', for the diagnosis and study of the time course of thromboembolic disease in a patient following total hip replacement. METHOD: One hundred micrograms of pentetic acid (DTPA)-P256 Fab' was labelled with 8 to 10 MBq of 111In chloride by incubation at room temperature for 15 min. After dilution in physiologic saline, the tracer was injected intravenously on the third and sixth days postoperatively. Imaging of the chest, pelvis, and legs was carried out at 24, 48 and 72 h following each injection. RESULTS: The first image four days after surgery demonstrated activity in the right heart which moved to the right pulmonary artery on the following day. Activity was seen in both femoral veins; on the left, this increased over two days, followed by a reduction on the seventh day after surgery, at which time new activity was seen in the right heart. After a further two days, this activity moved to the left pulmonary artery. The DVT was confirmed by venography and the pulmonary embolism (PE) by ventilation perfusion scan. CONCLUSIONS: 111Indium-labelled platelet-specific monoclonal antibody, P256 Fab', provides a technique for studying the natural history of thromboembolic disease and its treatment.

Aged↗
PubMed1992

Do technetium-99m hexamethylpropylene amine oxime-labeled leukocytes truly reflect the mucosal inflammation in patients with ulcerative colitis?

Twenty-five patients with ulcerative colitis and nine controls with macroscopically non-inflamed colon were investigated with technetium-99m hexamethylpropylene amine oxime-labeled leukocyte scintigraphy and colonoscopy with biopsies. The interval between leukocyte scintigraphy and colonoscopy was < or = 14 days in all patients with ulcerative colitis and < or = 30 days in eight of nine controls. Scintigrams were obtained at approximately 45 min and 4 h after injection of labeled leukocytes. One nuclear physician, one internist, and one pathologist graded blindly and independently of each other the degree of active inflammation in seven different colonic segments for each patient, using 4-grade scales for scans and macroscopically and histologically viewed inflammation, respectively. A positive correlation between endoscopic and histologic grading of all colonic segments and scan gradings for all subjects and for ulcerative colitis patients separately was found (all, p < 0.001). By means of kappa statistics, the inter-observer agreement between scintigraphic grading at 45 min and endoscopy was, for all subjects, 0.32 (95% confidence interval (CI), 0.20-0.44; p < 0.001) and, for patients with ulcerative colitis, 0.19 (CI, 0.07-0.31; p < 0.001). When 17 patients who had complete colonoscopies were divided into those with total, extensive, or distal colitis, leukocyte scintigraphy underestimated the extension of active inflammation. A simple scintigraphic scoring system reflects the colonic inflammation viewed endoscopically and histologically in patients with ulcerative colitis but underestimates the presence of active inflammation in individual colonic segments.

Adolescent↗
PubMed1992

A retrospective study of radiolabeled granulocyte kinetics in patients with systemic vasculitis.

Patients with systemic vasculitis, including Wegener's granulomatosis (WG) and microscopic polyarteritis (MP), may undergo white cell scanning for the investigation of infective complications and/or occult fever. In a retrospective study of 12 patients with systemic vasculitis (six each of WG and MP), all with renal disease, we observed increase diffuse lung radioactivity soon after the injection of 111In-labeled granulocytes or 99mTc-HMPAO-labeled leukocytes in all patients with WG and in three with MP. Lung activity was quantified by comparison with the liver or spleen. The lung:liver count rate ratio per pixel, 1-1.5 hr after injection, in patients with systemic vasculitis was 0.87 (s.d. 0.25), significantly higher (p less than 0.001) than the ratio 0.38 (0.13) in patient controls who had normal white cell scans. The majority of patients with systemic vasculitis had scintigraphic evidence of abnormal splenic function. Two had focal splenic defects, while 7 had increased labeled cell uptake. Nine of the patients with vasculitis showed cell migration into the gut, presumably as a result of vasculitis, and in 6 it was prominent. Focal nasal uptake was found in 5/7 patients with systemic vasculitis who had their heads imaged, and may be specific for WG. Although all patients had renal disease, there was scintigraphic evidence of diffuse parenchymal renal uptake of 111In-labeled granulocytes in only one (with MP). The presence of anti-neutrophil cytoplasmic antibodies did not correlate with any abnormality or with lung uptake. Systemic vasculitis is associated with abnormalities of granulocyte kinetics, particularly involving the lung and spleen.

Granulocytes↗
PubMed1992

Indium-111 whole-body retention: a method for quantification of disease activity in inflammatory bowel disease.

Quantification of disease activity in inflammatory bowel disease (IBD) has been by measurement of fecal excretion of 111In-granulocytes. The difficulties of this method prompted us to evaluate quantification of whole-body 111In retention, expressed as a percentage of whole-body activity at 3 hr following injection, as an alternative method. The patient stood in front of the uncollimated gamma camera at a distance of 4 m and counts were collected over 2 min. The geometric mean was taken of posterior and anterior counts and compared with a 111In standard. The lower limit of the 95% confidence interval for whole-body retention in normals was 90%. Forty-five studies were performed on 33 patients with IBD. They were assessed in two groups, one to whom routine instructions for the collection of feces were given (Group A) but who did not always comply. The other group received oral and written instructions and were also monitored during the collection period (Group B) and reported full fecal collection. Although in Group A the correlation between fecal excretion and whole-body retention was good (r = 0.7, n = 32; p less than 0.001), in Group B the relationship between fecal excretion and whole-body retention was significantly better (r = 0.95, n = 18; p less than 0.001). On average, 111In whole-body retention was consistent with findings obtained during imaging: 111In excretion (100-whole-body retention) was 7.8% +/- 4.9% in 5 normal scans, 10% +/- 5.9% in 17 (+) scans, 22.3% +/- 8% in 20 (++) scans and 57% +/- 16% in 8 ( ) scans. We conclude that imaging is more sensitive than whole-body retention and fecal excretion in the detection of disease, but for quantification, whole-body retention is an accurate reliable alternative to fecal excretion.

Adult↗
PubMed1991

Imaging of metastatic colorectal cancer with tumour-activated killer lymphocytes.

Adoptive immunotherapy may be useful for treating or visualising metastatic cancer. Lymphocytes were taken from 6 patients with metastatic colorectal cancer and cultured with cells from the patients primary tumour to produce tumour-activated killer (TAK) lymphocytes. We re-injected each patient with IIIIn-labelled TAK cells in order to visualise metastases. Images were taken with a gamma-camera for up to 48 h after injection. Metastases were revealed as early as 4 h in the lung and as late as 48 h in the abdomen. Liver images produced "cold" spots corresponding to metastatic lesions. Lymph nodes were not visualised. Re-injection of TAK cells raised against autologous colorectal tumours reveals the sites of metastases.

Abdominal Neoplasms↗