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Biomedical subjects

S H Saverymuttu

Publications and source records attributed to S H Saverymuttu.

At least 73 records · Page 4Linked to original sources

Assessment of disease activity in inflammatory bowel disease: a new approach using 111In granulocyte scanning.

111In leucocyte scanning yields images of diseased bowel in patients with inflammatory bowel disease. The technique has recently been improved by being made more specific for acute inflammation by the isolation and labelling of a pure granulocyte preparation. The value of 111In granulocyte scanning in monitoring response to steroid treatment was assessed in 22 patients with Crohn's disease or ulcerative colitis. After steroid treatment there was agreement between the change in the scan grade and the change in clinical disease activity in 18 of the 22 patients. Overall there was a significant correlation between the change in the scan grade and clinical improvement (r = 0.775, p less than 0.001). This study suggests that 111In granulocyte scanning can provide a rapid assessment of disease activity in inflammatory bowel disease.

Colitis, Ulcerative↗

Indium-111 tropolonate leucocyte scanning in the detection of intra-abdominal abscesses.

Indium-111 leucocyte scanning is established as an accurate method for localising intra-abdominal abscesses. With the currently available cell labelling techniques there is a variable and significant delay in localisation of abscesses which is a major disadvantage in comparison with ultrasound or computed tomography. We have examined the speed and accuracy of localisation of leucocytes labelled in plasma with a new chelating agent, indium-111 tropolonate, in 90 patients with suspected intra-abdominal abscess. In 50 patients a comparison with ultrasound was made. Nineteen patients had abscesses. The sensitivity and specificity of labelled leucocytes were 95% and 99%, respectively. Comparative results for ultrasound were 60% and 83%. In nine out of 10 patients with abscesses scanned sequentially from 40 min after return of the labelled cells, activity corresponding to the abscess was already visible on the 40 min scan. These results demonstrate that indium-111 plasma labelled leucocyte scanning is both rapid and an accurate method of detecting abscesses.

Abdomen↗

Lung transit of 111Indium-labelled granulocytes. Relationship to labelling techniques.

The early in vivo distribution of 111Indium-labelled granulocytes, recorded by dynamic imaging using a gamma camara and computer, varied according to the separation and labelling technique. Following i.v. bolus injection, 4 kinetic patterns could be identified: (A) rapid transit through the pulmonary vasculature, (B) delayed transit through the lung with clearance by about 30 min, (C) complete retention by the lung, for up to 10 min, followed by slow release over a period of 1 to 2 h, (D) delayed transit through the lung with a similar time course to (B) but with subsequent heavy liver uptake. Granulocytes labelled with 111In-tropolonate and maintained in plasma throughout the labelling procedure, whether injected as a 'pure' (separated by plasma-enriched density gradient centrifugation) or 'crude' (separated by differential centrifugation) preparation, displayed type A kinetics, thought to most closely represent the normal behaviour of granulocytes. 'Crude' cells labelled in saline with 111In-acetylacetonate displayed type B kinetics. 'Pure' cells isolated on Percoll-saline and labelled in saline with 111In-acetylacetonate displayed type C kinetics, thought to represent granulocyte 'stimulation' and/or damage, or type D kinetics, thought to represent severe damage. The importance is stressed of labelling granulocytes for kinetic studies with a technique that results in minimal alteration of cell behaviour.

Cell Movement↗

111Indium autologous leucocytes in inflammatory bowel disease.

A non-invasive method of imaging and assessing inflammatory bowel disease is described. 111Indium labelled leucocyte scans were performed on 33 patients with a wide variety of inflammatory bowel diseases and 25 control patients. All patients with moderate or severe inflammatory bowel disease had positive scans with localisation of abnormal activity corresponding to the sites assessed to be diseased by radiology in either small or large bowel. No false positives were recorded in the control patients. Faecal excretion of 111In labelled leucocytes was increased in patients with inflammatory bowel disease according to disease severity and correlated with disease activity assessed by serum C-reactive protein levels (r = 0.74, p less than 0.001) or in those patients with Crohn's disease by Crohn's Disease Activity Index (r = 0.78, p less than 0.001). These data suggest that 111In labelled leucocytes may be used to provide a safe, non-invasive method of imaging diseased bowel and objectively assessing disease activity.

Colitis, Ulcerative↗

Assessment of disease activity in ulcerative colitis using indium-111-labelled leukocyte faecal excretion.

A new method of assessing disease activity in ulcerative colitis has been developed utilizing indium-111-labelled granulocytes. Faecal 111In excretion after intravenous administration of labelled granulocytes ranged from 1.1% to 45% of the injected dose in patients with ulcerative colitis, showing significant differences between mild, moderate, and severely active groups. There was a significant correlation between faecal 111In excretion and a clinical index based on the Crohn's disease activity index (r = 0.79, p less than 0.001) and the erythrocyte sedimentation rate (r = 0.73, p less than 0.001). Quantitative faecal 111In-labelled granulocyte excretion is an objective and specific method of assessing disease activity in ulcerative colitis.

Adolescent↗

Quantitative fecal indium 111-labeled leukocyte excretion in the assessment of disease in Crohn's disease.

The assessment of disease activity in Crohn's disease involves determination of either clinical indexes (e.g., Crohn's disease activity index) or laboratory measurements (e.g., C-reactive protein and erythrocyte sedimentation rate). These have the disadvantage of being indirect and nonspecific correlates of gut inflammation. We have assessed disease activity in Crohn's disease by measurement of fecal leukocyte excretion after intravenous administration of either 111In-labeled mixed leukocyte or pure granulocyte preparations. With mixed leukocyte preparations, fecal excretion of radioactivity correlated with Crohn's disease activity index (r = 0.78, p less than 0.001) and C-reactive protein (r = 0.74, p less than 0.01). Using pure granulocytes, fecal 111In excretion (range 1.5%-52%) was much higher than with mixed leukocytes (range 0.1%-11.0%), showing significant correlations with Crohn's disease activity index (r = 0.731, p less than 0.001), C-reactive protein (r = 0.716, p less than 0.001), and erythrocyte sedimentation rate (r = 0.676, p less than 0.001). Quantitative fecal excretion of 111In-leukocytes is a new method of assessing disease activity in Crohn's disease, specific for bowel inflammation and suitable for objective assessment of disease activity in therapeutic trials.

Blood Sedimentation↗

Imaging of inflammation with indium-111 tropolonate labeled leukocytes.

Indium-111 tropolonate has recently been introduced as a new cell-labeling agent. It has the interesting property of labeling cells in plasma with high efficiency, and may therefore promote an improvement in viability of labeled cells. This paper describes our initial experience with In-111 tropolonate as a leukocyte label for abscess imaging. Pure populations of separated granulocytes, as well as crude leukocyte preparations, have been labeled. Of 101 studies performed, 51 were positive (no false positives) and 50 negatives, of which only two were false negatives. Localization in sites of inflammation was prominent and rapid. Of 36 positive studies, 27 were already positive at 40 min following injection and an additional nine at 3 hr. Of the other 15 positive studies, 11 were scanned for the first time at 3 hr, when they were positive. Granulocytes labeled with this agent in plasma showed minimal sequestration in lungs and liver, interpreted as indicating improved viability in comparison with cells displaying prolonged lung sequestration.

Abdomen↗

Measurement of granulocyte migration and accumulation in inflammation in man.

A method has been developed for studying granulocyte kinetics in inflammation. Autologous granulocytes isolated from whole blood and labelled with 111indium, without separation from plasma enriched media, localized rapidly in intra-abdominal abscesses and inflammatory bowel disease following intravenous reinjection. Utilizing a gamma camera interfaced to a computer for dynamic imaging, uptake of activity in the site of inflammation could be demonstrated from 10 min following injection. A quantitative estimate of the rate of granulocyte uptake in inflammatory foci, (early granulocyte accumulation index EGAI) was made by subtracting the gradient of the time activity profile, recorded over the inflammatory focus from that of the profile recorded over a similar sized control region, and expressing the difference in relation to the zero time intercept of the profile over the inflammatory focus. The EGAI showed a positive correlation with the ESR (sigma = 0.574; P less than 0.05) and, in the single patient studied twice, decreased following steroid therapy. This technique should prove useful in studying granulocyte kinetics in inflammation in man.

Abdomen↗

Indium-111 autologous leucocyte scanning: comparison with radiology for imaging the colon in inflammatory bowel disease.

Indium-111 autologous leucocyte scanning was compared with barium enema for assessing the extent of colonic disease in Crohn's colitis and ulcerative colitis. Scanning was shown to be as accurate as conventional radiology in colitis, reliably distinguishing active from inactive disease. The results suggest that 111In-leucocyte scanning is an accurate, non-invasive, alternative technique for imaging the extent of disease in colitis.

Colitis, Ulcerative↗

Animal maturity influences prostaglandin effects on gallbladder fluid transport and smooth muscle.

Prostaglandin (PG) A, E and F compounds applied serosally inhibited net fluid absorption and increased intraluminal pressure in guinea-pig isolated gallbladder. The inhibition was dose-dependent for a given animal body weight but sensitivity varied inversely with animal body weight; relative potencies were PGE2 greater than F2alpha greater than A1. In heavier animals the inhibition was preceded by an apparent increase in fluid absorption, due to fluid extrusion following muscle contraction. Net fluid secretion was observed at higher concentrations of PGE2 or F2alpha in lighter animals. Mucosally applied PGs less potently inhibited absorption, with relative potencies of PGE2 greater than A1 greater than F2beta greater than F2alpha. The spasmogenic effect was estimated by measuring intraluminal pressure (PGE2 greater than F2alpha greater than A1).

Aging↗

Effects of bicarbonate on fluid and electrolyte transport by the guinea pig gallbladder: a bicarbonate-chloride exchange.

Fluid transport and net fluxes of Na, K, Cl and HCO3 by guinea pig gallbladder were investigated in vitro. A perfused gallbladder preparation was devised to simultaneously study unidirectional fluxes of 22Na and 36Cl. The net Cl flux exceeded the net Na flux during fluid absorption in the presence of HCO3. This Cl excess was counterbalanced by a net HCO3 secretion: a HCO3-Cl exchange. PGE1 reversed the direction of fluid transport and abolished the net Cl flux. The magnitude of the HCO3 secretion remained unchanged, but shifted from a HCO3-Cl exchange to a net secretion of NaHCO3 and KHCO3. Furosemide inhibited both the HCO3-Cl exchange and HCO3 secretion after PGE1 without influencing fluid absorption. Ouabain inhibited the HCO3-Cl exchange as well as fluid absorption; only the effect on the HCO3 secretion was entirely reversible. Secreted HCO3 appeared not to be derived from metabolic sources since HCO3 secretion was abolished in a HCO3-free bathing medium. HCO3 secretion was also dependent on the Na concentration of the bathing fluid. Three lines of evidence are presented in favor of an active HCO3 secretion in guinea pig gallbladder. HCO3 is secreted against: (i) a chemical gradient, (ii) an electrical gradient and (iii) the direction of fluid movement under control conditions.

Absorption↗