Splenic deposition of platelets after liver transplantation.
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Biomedical subjects
Publications and source records attributed to L A Forstrom.
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The in vivo viability and functional integrity of filtered platelets were compared with those of nonfiltered platelets in a controlled study. On two occasions, after template bleeding time, 14 healthy volunteers underwent plateletpheresis and received 600 mg of aspirin. Autologous 111In-labeled platelets were transfused without further manipulation (control) on one occasion and after filtration on a second occasion. The filter was primed and flushed with a buffered 12.6-percent solution of ACD-A in 0.9-percent normal saline (pH 6.5). After transfusion, the bleeding time was measured at 1, 4, and 24 hours and platelet survival at 10 minutes; 1, 4, and 24 hours; and daily for 6 days. The decrease in the bleeding time was not significantly different from that after transfusion of nonfiltered platelets (p greater than 0.2). Filtering of platelets did not affect 1-hour in vivo recovery (filtered, 69.5%; nonfiltered, 66%: p = 0.56) or the platelet survival (filtered platelet t1/2 = 83.0 hours, nonfiltered platelet t1/2 = 82.9 hours: p = 0.96). It can be concluded that filtration does not adversely affect in vivo recovery, survival, or functional integrity of platelets.
High surgical mortality in patients with obstructive jaundice and sepsis have been attributed to reticuloendothelial system (RES) depression. The purpose of this study was to clarify the effects of mechanical biliary obstruction on RES clearance of pathogenic bacteria by comparing the phagocytic index (K) with the directly measured hepatic uptake of indium 111-labeled bacteria injected into the portal vein of normal dogs and dogs with partial (PBO) or complete biliary obstruction (CBO). No significant difference was observed between the K in normal dogs (0.19 +/- 0.08; n = 6) and that in dogs with PBO (0.24 +/- 0.06; n = 5) or CBO (0.21 +/- 0.03; n = 4). There was no significant difference in uptake of radiolabel by the liver among the three groups of dogs. In our model, biliary obstruction had no effect on hepatic RES function and may not represent a significant determinant of mortality in patients with obstructive jaundice.
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Polymorphonuclear neutrophilic granulocytes were separated from anti-coagulated whole blood using three techniques. The methods employed included volex sedimentation (VS), volex sedimentation with hypotonic lysis (VSHL), and Ficoll-Hypaque gradient separation (FH). The cells were labeled with 111In-oxine and 111In-tropolone. Studies were done with both blood from normal human volunteers and with canine blood. From the cell counts and differential, the harvested granulocytes, platelets, and red blood cells per milliliter of whole blood were calculated. Using the granulocyte chemotactic response to E. coli in agarose plates, the ratio of chemotactic migration to random migration (c.m./r.m.) was determined. Survival time for 111In labeled granulocytes were also determined in a canine model. The studies demonstrated that all procedures yielded 100% viability by the Trypan blue exclusion test. Chemotactic migration and leukocyte survival times were similar amongst all techniques. With the VSHL technique, there were significantly fewer red blood cells and platelets in the final preparation approaching the results of FH separation. The results suggest that for a relatively pure granulocyte preparation VSHL is an acceptable alternative to FH.
Indium-111 labeled leukocytes have been shown to be useful in the diagnosis of synthetic vascular graft infection. To minimize the potential effects of labeled red blood cells and platelets on image interpretation, the authors prepared purified autologous granulocytes (PG) from 84 ml of blood using Volex enhanced gravity sedimentation and Ficoll-Hypaque double density centrifugation. The labeling efficiency of PG with In-111 tropolone was 90 +/- 9% (mean +/- SD). Imaging was performed 18-24 hours following injection of approximately 445 microcuries of In-111 PG in 26 patients with suspected infection of vascular grafts that had been implanted 12 days to 12 years prior to the study. In ten patients with proven graft infection, seven had positive In-111 PG scans. Ten of 11 patients without infection had negative scans. In five patients with clinically equivocal findings, scan results were positive in one, negative in one, and equivocal in three. A false-positive scan occurred in a patient with an uninfected inflammatory pseudoaneurysm of an aortic graft. These results confirm an earlier report that In-111 PG imaging is a useful technique in the diagnosis of synthetic vascular graft infection.
We performed in vitro aggregation and indium-111 labeled platelet kinetic and biodistribution studies in seven patients with diabetes mellitus and in five control subjects. All subjects were male. All diabetic patients were poorly controlled at the time of study with blood glucose greater than 140 mg % and hemoglobin A1c greater than 10%. In vivo kinetic and biodistribution studies were performed following reinjection of autologous platelets labeled with indium-111 oxine in a dose of approximately 50 microCi (42-67 microCi). Images obtained at 4 and 24 h were computer-analyzed to determine splenic and hepatic uptake, and platelet survival times were calculated using four mathematical models. Unexpectedly, diabetic patients with fewer vascular complications tended to have shorter platelet survival times than patients with advanced vascular disease. However, no significant differences were observed between diabetic and control groups for any of the parameters of platelet function evaluated.
Thrombocytopenia occurs in postoperative liver transplant patients, with platelet counts reaching a nadir on the third postoperative day. Significant bleeding episodes are not uncommon during the first five days postoperatively when platelet counts are low. This thrombocytopenia may be the result of platelet sequestration in the newly grafted liver. The sequestration phenomenon does not appear to be on the basis of antiplatelet antibody activity. Further work defining the time course of this organ sequestration and evaluating the possible release of previously sequestered platelets back into the circulation need to be done. Also, it may be productive to study medications known to inhibit platelet activation (ie, cyclooxygenase inhibitors, prostacyclin, and calcium channel blockers) with the intent of interrupting platelet adhesiveness-sequestration at the time of recirculation of the newly grafted liver.
Rabbit peripheral blood and glycogen-stimulated peritoneal neutrophils were labeled with [111In]indium oxine and transfused intravenously into recipient rabbits with experimental abdominal abscesses due to Staphylococcus aureus. Peritoneal neutrophils harvested 4 hr after glycogen infusion localized within the abscesses to a greater extent than did peripheral blood neutrophils (P less than .002). In an in vitro chemotaxis under-agarose assay, peripheral blood neutrophils had greater random migration (P less than .002) and directed migration (P less than .01) than did peritoneal cells. In an in vitro glass slide adherence assay, peritoneal neutrophils were more adherent than were blood neutrophils (P less than .05). The discrepancy between in vivo and in vitro findings may be due to the increased adherence of peritoneal neutrophils. Glycogen-stimulated peritoneal neutrophils have been exposed in vivo to C5a, which is known to decrease migration and increase adherence in vitro of polymorphonuclear neutrophils; consequently, in vivo exposure of neutrophils to C5a may mean in vitro migration data may be misleading in predicting results in vivo.
In the 24 hours after coronary occlusion, some defects on thallium-201 images decrease in size. This study examined the mechanism of the decrease in defect size in dogs with experimental coronary occlusion. The left anterior descending coronary artery was permanently occluded in chronically instrumented awake dogs. Myocardial blood flow was measured with radioactive microspheres immediately before occlusion, 30 minutes, and 24 hours after occlusion. Thallium-201 was injected and imaging was performed 2 to 6 days before occlusion, 30 minutes, and 24 hours after occlusion. Two dogs, in which less than 1% of the left ventricle was infarcted, had no defects on the 30-minute postocclusion images. In four dogs the thallium-201 images did not change appreciably over 24 hours (group 1), while in three dogs the image defect size decreased (group 2). In groups 1 and 2 respectively the percent increase in blood flow to the hypoperfused area was: subendocardium 9 +/- 7% vs 31 +/- 15%; subepicardium 26 +/- 6% vs 47 +/- 2% (p less than 0.05). Therefore a decrease in the size of thallium-201 image defects occurred if a sufficient increase in collateral flow to the hypoperfused area took place in the first 24 hours after coronary occlusion. The defects appeared to decrease in size even in the absence of a detectable change in the lateral borders of the hypoperfused area.
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Indium-111-labeled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labeling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6 mCi of In-111-leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients.
We report the results of a new test, indium oxine in 111 scanning, in the diagnosis of postoperative infection. Indium 111 was used to label autologous polymorphonuclear leukocytes, which when reinjected migrate to sites of infection, inflammation, or both. Standard scintigraphy localizes the labeled inflammatory cells at these sites. Sixty-six scans were performed in 43 surgical patients. Thirty-seven scans were categorized as true-positive; 19 scans were categorized as true-negative. Therefore, the accuracy rate was 85%. Two scans (3%) in one patient represented false-positive results. Two scans (3%) were positive for inflammation but there was no infection present; this group was denoted as equivocal. Six scans (9%) were false-negative; false-negative scans are more likely in old lesions with poor blood supply and in areas that overlap regions of normal uptake. The noninvasive nature of the test, high accuracy rate, and ease of administration make it a potentially useful tool in the diagnosis of postoperative infection.
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Thallium-201 was found to be a reliable agent for detecting decreased myocardial perfusion in domestic pigs 1-4 hours after acute coronary occlusion. Substantial variation in myocardial-to-liver count ratios and diagnostic quality was observed in serial images performed in 3 normal pigs, although areas of 1-4 hours-old myocardial ischemia produced by acute circumflex coronary artery ligation in 6 pigs could be reliably detected by in vivo 201Ti imaging. After intravenous 201Ti administration, the animals were sacrificed and sections of normal and ischemic myocardium were counted in a scintillation well counter. The activity in the ischemic area in pigs averaged 12% of the activity in the normal area, and varied over a narrow range; in dogs the activity averaged 62% of normal, and varied over a wide range. The pig was a more consistent model than the dog.
The viability and functional integrity of saline- and ACD-saline-washed platelets were compared with those of unwashed platelets. After template bleeding time (TBT) was measured, 15 healthy volunteers underwent plateletpheresis and ingested 600 mg of aspirin. Autologous 111In-labeled platelets were transfused: unwashed (n = 5), washed with 0.9 percent saline solution (SS) (n = 5), and washed with a buffered 12.6 percent solution of ACD-A in 0.9 percent saline solution (n = 5). After transfusion, we measured TBT at 1, 4, and 24 hours; platelet survival at 10 minutes and 1, 4, and 24 hours and daily for 6 days; and the percentage of uptake in liver and spleen by quantitative whole-body radionuclide scintigraphy at 24 and 190 hours. We found that saline washing affected platelet recovery, 23.47 +/- 12 percent (p less than 0.001) as compared to 52.43 +/- 17 percent (p less than 0.002) for ACD-saline and 73.17 +/- 8 percent for control; that saline washing resulted in a greater liver uptake than control and ACD-saline-washed platelets (31.9 +/- 8% [p less than 0.001] vs 17.7 +/- 4.1 and 19.3 +/- 2.1% [p greater than 0.1], respectively); that, unlike control and ACD-saline-washed platelets, saline-washed platelets did not shorten bleeding time; and that neither type of washing affected survival. Although ACD-saline washing affects recovery, it also results in intact function, normal survival, higher recovery than SS platelets, and no significant liver uptake.