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Biomedical subjects

S H Saverymuttu

Publications and source records attributed to S H Saverymuttu.

At least 55 records · Page 3Linked to original sources
PubMed1985

Activated eosinophils in familial eosinophilic gastroenteritis.

Two siblings with eosinophilic gastroenteritis who presented with severe iron deficiency anemia and hypoalbuminemia associated with varying degrees of mucosal damage are described. Using a monoclonal antibody to the secreted form of eosinophil cationic protein, we demonstrated activated degranulating eosinophils in the gastrointestinal mucosa that correlated with the degree of histologic damage. This finding suggests that eosinophils may have a primary role in the tissue damage in this condition. Oral disodium cromoglycate (Nalcrom) failed to alter the clinical, radiologic, and histologic abnormalities. Prednisolone, however, was beneficial in 1 case but did not completely reverse the abnormalities.

Adolescent↗
PubMed1985

Splenic pooling of granulocytes.

The intrasplenic kinetics of granulocytes, isolated in plasma and labelled in plasma with 111In-tropolonate, have been studied in normal subjects, patients with negative studies for inflammatory disease and patients with positive studies, with the aim of identifying the nature of splenic activity seen after 111In-labelled granulocyte administration. Up to 40 min after injection, 111In activity was visible only in major blood vessels, liver and spleen, with slight, abnormal activity visible in most of those with positive scans. The time courses of uptake of hepatic and splenic activity were different, with liver activity rapidly reaching a plateau and splenic activity increasing mono-exponentially to a plateau achieved between 20 and 40 min. The clear difference between the shapes of the hepatic and splenic uptake curves and the magnitude of the splenic uptake rate constant indicated that splenic activity represented reversible uptake. The application of deconvolution analysis to the blood and splenic time-activity curves generated a splenic retention (or washout) curve consistent with dynamic exchange of granulocytes between blood and spleen. The slope of this curve indicated an intrasplenic granulocyte transit time of 9.3 (+/- SE 0.6) min. Taking splenic activity to be reversible, comparison of the 111In signal from the spleen 40 min after injection of 111In-labelled granulocytes with that given from the spleen after the injection of 111In-labelled erythrocytes (relative to their respective blood levels) indicated that intrasplenic granulocyte transit time was 14.4 (+/- SE 1.1) times that of erythrocytes. Based on actual erythrocyte time, this corresponds to a granulocyte transit time of 8.6-11.5 min, in close agreement with the estimate based on deconvolution analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Colitis↗
PubMed1985

Is the pattern of inflammatory bowel disease different in the elderly?

The clinical course of inflammatory bowel disease in elderly patients has been reviewed. The natural history of ulcerative colitis and Crohn's disease in the elderly is similar to that in the young with the usual wide spectrum of severity of disease. Such inflammatory bowl disease responds well to medical treatment in the majority of elderly patients, and surgical intervention is only required rarely for complications or unresponsive disease. Reports of a more serious clinical course in older patients were not substantiated.

Aged↗
PubMed1985

The kinetics of 111indium distribution following injection of 111indium labelled autologous granulocytes in man.

The kinetics of human autologous granulocytes, separated and labelled with 111In without isolation from plasma, have been studied in subjects with and without sepsis with the aim of identifying the fate and sites of destruction of granulocytes in man. In subjects without inflammatory disease, 111In granulocyte recovery in faeces, urine and saliva over 4 d was less than 1% of the dose, so that the activity visualized by the gamma camera represented almost 100% of the dose. On images taken at 24 and 48 h, this activity was distributed between spleen, bone marrow and liver, with foci of additional abnormal activity in subjects with inflammatory disease. Splenic activity fell between 40 min and 24 h, consistent with the presence of a splenic granulocyte pool, but remained constant after 24 h. Since granulocyte clearance from the blood was predominantly completed by 24 h, the residual splenic activity at that time reflected splenic granulocyte destruction. In patients with sepsis, the fall in splenic activity was greater than in those without, implying diversion of granulocytes from splenic destruction to tissue utilization when inflammation is present. Bone marrow activity increased between 40 min and 24 h and then remained stable. Granulocytes that were extensively manipulated in saline prior to labelling failed to localize in marrow, suggesting that visualization of the latter reflected destruction of intact, normal granulocytes. Although the changes in splenic and marrow activities terminated at 24 h, at which time granulocyte clearance from blood was at least 80% completed, plasma 111In remained essentially unchanged between 40 min and 48 h at less than 5% of the dose, discounting it as the source of splenic and marrow activities.

Bone Marrow↗
PubMed1985

The kinetics of unmatched and HLA-matched 111in-labelled homologous platelets in recipients with chronic marrow hypoplasia and anti-platelet immunity.

The kinetics of homologous platelets, labelled in plasma with 111In-tropolonate, have been studied in five recipients with chronic marrow hypoplasia and severe thrombocytopenia, who were refractory to platelet transfusions as a result of alloimmunization. Mean platelet life span (MPLS), recovery, plasma 111In level and splenic and hepatic uptake kinetics were studied on two occasions, one using HLA-matched platelets and the other unmatched platelets. In each case, recovery of labelled platelets at 1 h post-injection and MPLS improved with HLA matching, although this improvement was highly variable. Only two of the five subjects would have derived any significant benefit from HLA-matched as compared with unmatched platelet transfusions. It was concluded that the need exists for additional cross-matching procedures, possibly related to platelet specific antigens, in patients who remain refractory to platelet transfusion.

Adolescent↗
PubMed1985

Granulocyte migration in ulcerative colitis.

Although histologically relapses in ulcerative colitis are characterized by an intense granulocyte infiltrate, there is evidence both from in vitro function tests and skin window migration studies in vivo that there is defective granulocyte function in ulcerative colitis. We have recently developed a method for non invasively monitoring granulocyte migration to sites of inflammation using indium-111-labelled granulocytes, and have used this technique in fifteen patients with ulcerative colitis. In all fifteen cases there was rapid migration of indium-111-labelled granulocytes to inflamed bowel within 10 min of return of the labelled cells. This study provides no support for a significant granulocyte migration defect in ulcerative colitis.

Adolescent↗
PubMed1985

Quantification of the distribution of the marginating granulocyte pool in man.

The kinetics of autologous granulocytes, separated from whole blood and labelled with 111In-tropolonate with continuous maintenance in plasma, have been studied in man, using a gamma camera and computer, with the aim of quantifying the distribution of the marginating granulocyte pool (MGP). We have used 3 approaches: dynamic gamma camera imaging immediately following i.v. injection of labelled cells, comparison of the activity signal from 111In-granulocytes with that from previously injected 111In-labelled red cells and absolute quantification of 111In present in liver, spleen and blood. Deconvolution analysis of the hepatic and peripheral blood time activity curves indicated that hepatic granulocyte transit time was 2.5 +/- SE 0.14 min. By comparison with 111In red cells, hepatic transit time was calculated to be 7.4 +/- SE 0.82 that of red cells, which, assuming an hepatic red cell content of 6% that of the total red cell mass, is equivalent to a transit time of 1.8 min. By comparison with 111In red cells, lung granulocyte transit time as a factor of red cel transit time was 5.4 +/- SE 0.7 at 5 min and 2.5 +/- SE 0.13 at 40 min after granulocyte injection. Using these kinetic data, in combination with previously published values for splenic granulocyte transit time, it was calculated that, 5 min after injection, the MGP accounted for 54% of the total blood granulocyte pool (TBGP), was 90% filled, and was distributed between spleen (19%), liver (26%), lung (33%) and the remainder of the body (22%). At 40 min, the MGP accounted for 60% of the TBGP, had equilibrated with the circulating granulocyte pool (CGP), and was distributed between the spleen, liver, lung and remainder of the body according to the following respective percentages: 35, 25, 10 and 30. The total granulocyte contents of the spleen and liver calculated on the basis of the kinetic data were 21% and 22% respectively and in broad agreement with the values, 34 and 23% respectively, calculated from quantitative scanning. It was concluded that about 70% of the body's MGP was present in the spleen, liver and lung. If the MGP is itself 60% of the TBGP then only about 18% of the TBGP marginates in extra-hepatosplenopulmonary sites.

Cell Adhesion↗
PubMed1985

The kinetics of short-lived indium-111 radiolabelled platelets.

We have studied the kinetics of autologous 111In-labelled platelets in patients with reduced platelet life span (less than 4.5 d), most of whom were thrombocytopenic, and of homologous 111In-labelled platelets in patients with severe thrombocytopenia. Intrasplenic platelet transit time (t) was calculated by compartmental and deconvolution analysis. In patients with a mean platelet life span of less than a few h, compartmental analysis may not be valid and so only deconvolution analysis was applied. There was a close correlation between values of t given by the two approaches (r = 0.88, n = 18, P less than 0.001). In some patients with severely reduced mean platelet life span (MPLS), the deconvolved splenic platelet clearance curves appeared to approach an asymptote, the relative magnitude of which was indicative of the irreversible extraction fraction by the spleen of incoming platelets. In other patients with severely reduced MPLS resulting from abnormal intra-hepatic platelet destruction, the deconvolved splenic curves resembled the normal. The intrasplenic platelet transit time showed no clear relationship with other parameters. It was concluded that platelet pooling within the spleen is normal in patients with reduced platelet life span, including idiopathic thrombocytopenic purpura, even when the predominant site of destruction is the spleen, and that platelets are not delayed in transit through the spleen in preparation for their removal from the circulation and ultimate destruction.

Blood Platelets↗
PubMed1985

In vivo assessment of granulocyte migration to diseased bowel in Crohn's disease.

It has been suggested, on the basis of impaired granulocyte migration to skin windows, that there is a fundamental granulocyte defect in Crohn's disease. In vitro tests of granulocyte function have, however, failed to confirm this. We have studied granulocyte migration to inflamed bowel in Crohn's disease using a new approach which utilises dynamic gamma camera imaging after injection of 111In labelled autologous granulocytes. In 20 of 22 studies there was rapid migration to diseased bowel, compatible with no migration delay. Only two patients showed delays in migration of 12 and 15 minutes respectively, but neither had any clinical characteristics to distinguish them from the other 20 patients. This study shows that the majority of patients with Crohn's disease in relapse have rapid granulocyte migration to diseased bowel and provides evidence against a significant migration defect in this condition.

Cell Movement↗
PubMed1985

111Indium autologous granulocytes in the detection of inflammatory bowel disease.

Indium leucocyte scanning and measurement of faecal Indium leucocyte excretion are techniques which have recently been introduced for assessing patients with inflammatory bowel disease. The methodology has recently been made more specific for acute inflammation by labelling pure granulocytes rather than the mixed leucocyte preparation. To determine the accuracy of this modified technique in detecting inflammatory bowel disease, we have prospectively compared Indium granulocyte scanning and faecal In granulocyte excretion with rectal histology and contrast bowel radiology as screening procedures in 100 patients with suspected inflammatory bowel disease. Thirty three patients were shown to have inflammatory bowel disease - 24 with Crohn's disease and nine with ulcerative colitis or indeterminate colitis. Overall the respective sensitivities for detecting inflammatory bowel disease were 97% for faecal Indium granulocyte excretion, 94% for Indium granulocyte scanning, 79% for radiology and 70% for rectal histology. The superiority of In granulocytes over radiology and rectal histology in detecting inflammatory bowel disease was, in the main, due to the difficulty in diagnosing Crohn's with conventional techniques. Although three of the patients with ulcerative colitis and indeterminate colitis had normal sigmoidoscopic appearances - all had abnormal rectal histology. No patient with a non-inflammatory bowel disorder had a positive In granulocyte scan or a raised faecal excretion. These results show that investigations using In granulocytes are accurate in identifying inflammatory bowel disease and offer important advantages over conventional procedures for detecting Crohn's disease.

Colitis, Ulcerative↗
PubMed1985

Indium 111 autologous leucocyte scanning in lobar pneumonia and lung abscesses.

Indium 111 leucocyte scanning was used to examine the kinetics of granulocyte localisation in five patients with lobar pneumonia and four patients with lung abscess. Lung abscesses showed dense accumulation of labelled granulocytes within four hours of injection. In contrast, in all cases of lobar pneumonia granulocytes failed to accumulate over a period of up to 24 hours despite evidence of adequate perfusion and of uptake in inflammation elsewhere. These results suggest that the recruitment of granulocytes to lobar pneumonia may be terminated early in its clinical course.

Cell Movement↗
PubMed1985

Watery diarrhea in a patient with myasthenia gravis, thymoma, and immunodeficiency.

An elderly man with thymoma, myasthenia gravis, and hypogammaglobulinemia developed profuse watery diarrhea. Infusions of gamma-globulin caused the diarrhea to resolve. The patient succumbed to fulminant bronchopneumonia. At necropsy he was found to have widespread cytomegalovirus infection with duodenal and ileal ulceration, subtotal villous atrophy, marked nonspecific inflammation of the small intestine and bronchopneumonia. In addition Herpes simplex infection and invasive candidiasis were present. Patients with immunodeficiency are susceptible to a variety of gastrointestinal pathogens, particularly viral.

Agammaglobulinemia↗
PubMed1984

Comparison of fecal granulocyte excretion in ulcerative colitis and Crohn's colitis.

Impaired granulocyte migration has been suggested to be present in Crohn's disease on the basis of in vitro granulocyte function tests and in vivo skin window studies. This idea is supported by the impression histologically that the acute inflammatory infiltrate in diseased bowel is less in Crohn's disease than ulcerative colitis. We have developed a method of quantitating the acute inflammatory infiltrate in inflamed bowel by measuring fecal indium-111 granulocyte excretion and have compared this assessment in patients with ulcerative colitis and Crohn's colitis matched for disease activity. For equivalent disease groups in ulcerative colitis and Crohn's colitis, there was no significant difference between fecal granulocyte excretion. These findings provide no support for the contention that there is a reduced granulocyte infiltration in Crohn's disease.

Colitis, Ulcerative↗
PubMed1984

The interpretation of platelet kinetic studies for the identification of sites of abnormal platelet destruction.

The kinetics of platelets labelled with 111In have been studied in a series of 175 subjects including 18 normal volunteers, and 12 patients with idiopathic thrombocytopenic purpura (ITP), but excluding patients in whom there was scintigraphic evidence of intravascular platelet consumption. From analysis of the kinetics, the following parameters were calculated: splenic blood flow (SBF), intrasplenic platelet transit time (t-), splenic platelet pool capacity (expressed as a percentage of the total circulating platelet population), the fraction of the dose of labelled platelets ultimately destroyed in the spleen and the mean platelet life span (MPLS). SBF increased with increasing spleen size up to values of 25% total blood volume (TBV) per min. Some patients with immune complex related diseases were identified with elevated SBF (up to 24% TBV min-1) but without significant splenomegaly. Patients with cardiac decompensation had reduced SBF relative to spleen size. t- showed no relationship with spleen size. It tended to fall in patients who had high SBF relative to spleen size and to rise in those with low SBF relative to spleen size; i.e. it was inversely related to splenic perfusion (flow per unit tissue volume). The splenic platelet pool capacity is dependent on platelet input (SBF) and splenic platelet clearance (reciprocal of t-), and showed a close relationship with spleen size. When all subjects except those with ITP were considered, splenic platelet destruction showed a good correlation (r = 0.70, n = 42, P less than 0.001) with the splenic platelet pooling capacity. The ratio of the fraction of platelets destroyed in the spleen to the fraction pooling there, the D/P ratio, was approximately unity and did not appear to vary with MPLS, spleen size or the patient's condition, except in ITP where it varied between about 0.5 and 2. This variation in ITP was thought to be the result of an immune mediated re-direction of reticulo-endothelial platelet destruction. It is suggested that the D/P ratio, rather than the absolute quantity of 111In labelled platelets destroyed in the spleen, may be a more useful predictor of response to splenectomy since it takes into account the observed, appropriate, tendency for the spleen to destroy platelets in proportion to its platelet pooling capacity.

Blood Flow Velocity↗
PubMed1984

Noninvasive investigation of the gastrointestinal tract in collagen-vascular disease.

We have investigated the use of 111Indium granulocyte scanning, which would be expected to identify areas of perivascular or generalized neutrophil infiltration, in patients with collagen-vascular diseases suffering from either gastrointestinal symptoms (diarrhea or abdominal pain in 15 patients) or otherwise unexplained fever (six patients). Among patients with gastrointestinal symptoms, seven of 15 had positive scans suggesting large or small bowel involvement--three of three patients with Behcet's syndrome, four of five with vasculitis, no patient in six with systemic lupus erythematosus, and no patient with Churg-Strauss syndrome. Among patients without gastrointestinal symptoms, only one patient with polyarteritis nodosa had a positive scan, showing both large and small intestinal involvement. White cell scanning offers a noninvasive, readily tolerated technique for identifying inflammatory involvement of the intestine in patients with collagen-vascular disorders. Gastrointestinal involvement is rare in the absence of symptoms; and among symptomatic patients, inflammatory involvement of the gut is more likely to be found in patients with vasculitis or Behcet's.

Abdomen↗
PubMed1984

A functional comparison of IIIindium-labelled elicited peripheral blood neutrophils and peritoneal neutrophils in the rat.

A functional comparison between elicited peripheral blood neutrophils has been made in vivo and in vitro. Preliminary experiments showed that separation of peripheral blood cells on a metrizamide gradient yielded too few neutrophils for efficient radiolabelling with indium (In): hence a mixed cell preparation comprising 80% neutrophils was elicited in the peripheral blood of adult male rats by the administration of endotoxin (0.25 mg i.a.) and cobra venom factor (200 microliter i.p.) 20 h before. Peritoneal neutrophils were collected 4 h after the i.p. injection of 6 ml thioglycollate. Both populations differed markedly from normal peripheral neutrophils on the in vitro testing of random locomotion, chemotaxis and phagocytosis of Candida. After labelling with IIIIn-tropolonate, a greater proportion (mean = 8%) of peripheral blood cells localized to an E. coli/Freund's complete adjuvant-induced abscess compared with peritoneal neutrophils (mean = 3%). The abscess could be visualized externally by scanning with both cell preparations, but the distribution of activity differed markedly. The greater hepatic sequestration of peritoneal neutrophils suggested cell damage or activation. To overcome the difficulty of harvesting normal peripheral blood neutrophils in the rat, either of these populations can be used to follow the kinetics of inflammation. However, elicited peripheral blood cells yield a higher proportion of responding cells.

Abscess↗
PubMed1984

111Indium leucocyte scanning in ampicillin-associated right-sided hemorrhagic colitis.

Hemorrhagic colitis is a rare but well-recognized complication with ampicillin or penicillin derivative treatment. Early colonoscopy has been advocated in establishing the diagnosis by demonstrating the characteristic pattern of only right-sided involvement and so distinguishing it from other colitides. We report a patient who developed colitis after amoxycillin therapy in whom 111Indium leucocyte scan demonstrated right-sided colitis which alerted us to the diagnosis. Discontinuation of the antibiotic resulting in rapid improvement, and return of the 111Indium leucocyte scan to normal in this patient suggests that ampicillin-associated colitis should not be considered purely as a hemorrhagic disease but may in some cases have an inflammatory component.

Acute Disease↗