GM-CSF expands the eosinophilic compartment in chronic idiopathic neutropenia.
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Biomedical subjects
Publications and source records attributed to J Kutti.
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Total nuclear DNA content and nuclear size of megakaryocytes were studied in biopsies of the iliac bone marrow of individuals with normal or increased platelet counts. The DNA content was determined using Feulgen cytophotometry of bone marrow smears and the nuclear area by morphometric analysis of megakaryocytes of bone marrow sections. The mean DNA content and the mean nuclear area were both significantly larger in megakaryocytes of patients with thrombocytosis as a result of myeloproliferative disease than in patients with secondary thrombocytosis as well as in two control groups of individuals with normal platelets counts, one comprising healthy volunteers, the other with various non-haematological disorders. There was a statistically significant correlation between the DNA content and nuclear area of the megakaryocytes (r = 0.92) in the entire group of bone marrows studied.
Vascular prostheses in humans do not endothelialize spontaneously. In the present study we explored the feasibility of seeding autologous endothelial cells into prostheses implanted in patients undergoing reconstruction of the infrarenal aorta. In 22 patients one limb of an aortic Dacron bifurcation prosthesis was seeded with autologous endothelial cells harvested from the distal portion of the saphenous vein. The other limb was sham-seeded with culture medium only. The effect of seeding was studied by use of indium 111 radiolabeled platelets and external gamma camera scanning at 1, 4, and 12 months after surgery. No complications ascribable to the seeding procedure were seen. During the first year after surgery a gradual decrease in platelet accumulation occurred over the whole vascular prosthesis. At all time points studied the seeded graft limbs exhibited significantly less deposition of radiolabeled platelets than did control limbs. The observed difference in platelet accumulation on autologous endothelial seeding-treated graft segments merits further investigation of this technique in humans.
In 120 healthy humans (58 males and 62 females) possible differences in platelet aggregability were investigated with respect to age and sex. By using a narrow range of final ADP concentrations (0.2-1.0 microM) primary and secondary aggregation were evaluated. The rate of primary aggregation was shown to be significantly related to increasing age and this was true for both sexes. As regards secondary aggregation the same pattern was seen in the group of male subjects. Thus, among the youngest (less than 34 years) the frequency of secondary waves was only one third of that encountered among the oldest (greater than 50 years). No similar association was detectable among the female subjects. The present study calls attention to some important issues which should be considered in platelet aggregation studies; the interpretation of data obtained from such studies invariably requires a careful selection of appropriate age- as well as sex-matched control groups.
By using 111In-labelled platelets and dynamic gamma camera scintigraphy, platelet production rate and intrasplenic platelet kinetics were determined in 13 patients at 1 and 4 months after aortic reconstructive vascular surgery with implantation of dacron prostheses. A significant decrease in platelet production rate and venous platelet count was recorded over time after surgery. Irrespective of whether the exchangeable splenic platelet pool was estimated from initial recovery of platelet-bound radioactivity or from compartmental analysis, the size of this pool was significantly lower at the first study; a change in intrasplenic platelet transit time accounted for the observed difference. Platelet mean life-span increased over time after surgery but the difference between the duplicate studies was not statistically significant. It can be concluded that there is a reduction of platelet production rate and venous platelet count over time after major reconstructive vascular surgery. The early postoperative elevation in the platelet count is mainly the result of an increased platelet production and to a lesser degree due to redistribution of platelets between the splenic platelet pool and general circulation.
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It has previously been demonstrated that patients with infantile autism demonstrate impaired in vivo platelet behaviour. Therefore, in 14 children (13 boys and 1 girl) with infantile autism (aged 2-14, mean 6 years) and 12 healthy control boys (aged 6-15, mean 11 years) we studied in vitro platelet reactivity using ADP- and collagen-induced platelet aggregation. In each child a total of 7 different final concentrations of ADP and 4 different concentrations of collagen were employed. At all concentrations of ADP and collagen used the autistic children consistently exhibited diminished platelet aggregability; the differences, however, did not reach statistical significance. Therefore a wider panel of in vitro tests is apparently required and a larger group of patients be studied to help elucidate the functional/metabolic platelet defect met in infantile autism.
Autologous endothelial seeding (AES) of vascular prostheses in dogs increases thrombus-free surface and improves prosthetic prostacyclin production, patency, and the ability to withstand hematogenous challenge with bacteria. No such information is available in human subjects. In the present study one limb of an aortic Dacron bifurcation prosthesis was seeded with autologous endothelial cells (ECs) harvested from the distal portion of the saphenous vein by enzymatic treatment. The deposition of indium 111-labeled platelets on the vascular prostheses was studied 1 and 4 months after operation. In seven of nine patients seeding resulted in decreased accumulation of radiolabeled platelets compared with sham-seeded control limbs (p less than 0.04), when studied 1 month after surgery. A decrease in platelet accumulation occurred over the whole prosthesis between 1 and 4 months, and no significant difference was noted at 4 months between seeded and nonseeded graft limbs. Although the seeding density was very low (440 ECs/cm2), the observed difference in platelet accumulation for AES-treated graft limbs in the early postoperative course merits further investigation of this technique in human beings.
In 14 patients with acute myocardial infarction, a 24-hour Iloprost infusion was started with a mean delay of 309 +/- 22 minutes from onset of symptoms. Patients were haemodynamically monitored with a pulmonary artery catheter and an arterial cannula. The dose of Iloprost was 1-4 ng kg-1 min-1 and titrated according to blood pressure and systemic vascular resistance. When 2.0-4.0 ng kg-1 min-1 of Iloprost were infused, 5 out of 10 patients required dose reduction due to hypotension, nausea or both. However, in all patients the infusion period was completed as planned. Acute reductions of systolic blood pressure and vascular resistance were seen, whereas stroke volume increased and heart rate remained unchanged. The infusion of Iloprost caused profound inhibition of ADP-induced platelet aggregation but no significant changes in plasma values for platelet-specific proteins or thromboxane B2 were recorded. It is concluded that it was possible to safely administer Iloprost over 24 hours in the early phase of acute myocardial infarction and profound anti-aggregatory effects were observed. These findings should be evaluated in a controlled study.
The relationship between the splenic blood flow and the intrasplenic platelet kinetics on the one hand, i.e. the two factors which govern the size of the exchangeable splenic platelet pool, and the spleen size on the other were assessed in 21 patients afflicted with haematologic disorders and variable splenomegaly. The splenic blood flow and intrasplenic platelet kinetics were measured using 111In-labelled platelets and compartmental analysis of their equilibration between circulating blood and splenic pool; the spleen size was determined by scintigraphy using 99mTc-labelled stannous colloid. Significant correlations were recorded between the spleen size and the splenic platelet pool size (r = 0.76; P less than 0.001) and between the spleen size and the splenic blood flow (r = 0.56; P less than 0.01). Splenic perfusion decreased significantly with increasing spleen size, but there was no relationship between the spleen size and the intrasplenic platelet transit time. However, an association was present between splenic perfusion and intrasplenic platelet transit time (r = -0.44; P less than 0.05). It is concluded that the splenic blood flow is the major determinant of the size of the exchangeable splenic platelet pool in splenomegalic states, and that the determination of spleen size using 99mTc-scintigraphy gives a rough estimation of the pool size. Splenic perfusion appears to be one of the factors which determine the intrasplenic platelet transit time.
The effect of an adrenaline infusion on the venous platelet count, splenic blood flow and intrasplenic platelet kinetics was investigated in seven healthy male volunteers by using 111In-labelled platelets and dynamic gamma camera scintigraphy. The infusions were administered in two different doses, 0.2 microgram/kg/min and 0.1 microgram/kg/min, respectively. Regardless of the given dose, adrenaline was found to markedly decrease the splenic blood flow, decrease the exchangeable splenic platelet pool size and to prolong the intrasplenic platelet transit time. In response to the higher dose of adrenaline the splenic blood flow was 1.3 +/- 0.5 (SD) % of total blood volume per min and the intrasplenic platelet transit time 17.3 +/- 2.3 (SD) min. In contrast, after termination of infusion, the splenic blood flow was 7.0 +/- 2.1 (SD) % of total blood volume per min and the intrasplenic platelet transit time was 11.5 +/- 1.5 (SD) min. The present results firmly demonstrate that the splenic blood flow is the immediate variable governing the size of the exchangeable splenic platelet pool, and that the adrenaline-induced depletion of the splenic platelet pool is a consequence of the splenic blood flow reduction. Finally, the splenic perfusion appears to be a major determinant of the intrasplenic platelet transit time.
The effect of a constant isoprenaline infusion on the venous platelet count, splenic blood flow and intrasplenic platelet kinetics was investigated in 6 healthy male volunteers. The study was carried out using autologous 111In-labelled platelets and dynamic gamma camera imaging of the initial distribution of radiolabelled platelets between blood and splenic platelet pool. The isoprenaline infusions were administered i.v. over 30 min in a dose of 0.03 micrograms/kg/min. These infusions significantly increased the splenic blood flow and the size of the exchangeable splenic platelet pool. Concomitantly, there was a decrease of labelled as well as unlabelled platelets in the peripheral blood. The intrasplenic platelet transit time was not affected. Before start of infusion, the splenic blood flow was 6.1 +/- 2.9 (SD) % of total blood volume/min and the splenic platelet pool size 34 +/- 9 (SD) %. During infusion the corresponding values were 8.7 +/- 3.9 (SD) and 41 +/- 11 (SD), respectively. It is concluded that an i.v. infusion of isoprenaline enhances splenic pooling of platelets as a result of an increase in splenic blood flow.
40 young healthy male volunteers (20 habitual smokers and 20 non-smokers) were investigated with respect to platelet reactivity, plasma fibrinogen and coagulation factor VIII. Smokers had significantly lower systolic blood pressures and higher venous platelet counts. The results for ADP-induced platelet aggregation, plasma concentrations for the 2 alpha-granule proteins, beta-thromboglobulin and platelet factor 4, did not differ between the 2 study groups involved; nor was there any difference between serum thromboxane B2 formation or plasma factor VIII:C activity. However, as compared to non-smokers, plasma fibrinogen levels were significantly higher among the smokers.
The aim of this study was to obtain a critical evaluation of a simple method for labelling platelets with 111In-oxine. All experiments were carried out on healthy volunteers. 65 +/- 7 (SD) % of the platelets in collected blood were labelled and reinjected. As compared to control experiments, only in response to a low final ADP concentration (1.0 mumol/l) did 111In-labelled platelets show reduced in vitro aggregability. The mean platelet volume for 111In-labelled platelets was slightly lower than the mean platelet volume in whole blood. The results for initial platelet recovery and platelet mean lifespan closely agreed with those of other studies in which considerably higher platelet extraction from whole blood was obtained. After injection, the splenic uptake and blood disappearance of 111In-labelled platelets followed a monoexponential function with almost identical rate constants. By compartmental analysis of the equilibration of platelets between blood and spleen, the splenic blood flow was estimated to be 4.8 +/- 1.9 (SD) % of the total blood volume/min; the intrasplenic platelet transit time was 9.7 +/- 1.6 (SD) min, and the exchangeable splenic platelet pool 31 +/- 8 (SD) %. Highly significant relationships were present between the splenic blood flow and the splenic platelet pool size, as well as between the splenic blood flow and the initial platelet recovery. It is concluded that the requirements for adequate interpretation of platelet kinetics are well met with the present method for harvesting and labelling of platelets.
At our hospital, 47 out of 184 consecutive splenectomies performed over 7 recent years were carried out on patients afflicted with various hematologic diseases. The results of these 47 splenectomies were the subject of a careful retrospective analysis. The majority of the splenectomies (81%) were therapeutic. Cytopenia, particularly thrombocytopenia, was the most common indication for surgery. As a whole, good therapeutic responses with rapid improvements in peripheral blood picture and/or diminished symptoms of pressure discomfort from an enlarged spleen were obtained. There was no peri- or postoperative mortality; 23% major and 26% minor postoperative complications were recorded. In patients with perioperative bleeding and various postoperative complications, the spleens were larger than in subjects who run an uneventful peri- and postoperative course. During the follow-up period, 4 septicemias occurred in 3 patients. In 2 of these patients, the septicemias coincided with a cholecystitis and a pneumonia, respectively. None of the infections was lethal. It is concluded that elective splenectomy for hematologic disease in well selected and carefully prepared patients is beneficial and can be performed without mortality or major hazards.
The splenic blood flow, intrasplenic platelet kinetics and spleen size were determined in 8 females with systemic lupus erythematosus (SLE), all without signs of active disease, by using gamma-camera scintigraphy with 111In-labelled platelets and 99mTc-stannous colloid. The results for splenic blood flow, intrasplenic platelet transit time and splenic platelet pool size, obtained by compartmental analysis of the initial distribution of radiolabelled platelets between blood and spleen, did not differ from those of a control group. In all SLE patients the spleen size was within normal limits. There was a significant relationship between the spleen volume and the splenic platelet pool size (r = 0.75; p less than 0.05), and between the spleen volume and splenic blood flow (r = 0.76; p less than 0.05). A borderline, inverse correlation was present between an estimate of splenic perfusion and intrasplenic platelet transit time (r = 0.62; p = 0.1). It is concluded that the splenic function, measured as splenic blood flow and intrasplenic platelet kinetics, is not disturbed in SLE patients without active disease.
In 31 women who had survived their first acute myocardial infarction (MI) studies of platelet reactivity were related to coronary angiographic findings. The results were compared to those obtained from 38 age-matched control women. According to the cardioangiographic findings the group of MI was subdivided into: 9 patients with 1-vessel disease (VD), 10 patients with 2-VD, and 5 patients with 3-VD; 7 subjects did not reveal significant coronary stenosis. When each of these 4 subgroups of MI-patients were compared with the control material significant difference with respect to PF4 was found only for subjects with 1-VD (20.0 +/- 4.8 vs. 10.3 +/- 0.6 ng/ml). As regards BTG the difference was significant for 1-VD and 2-VD patients (69 +/- 12 and 59 +/- 3, respectively vs. 40 +/- 2 ng/ml). The cumulative frequency for secondary aggregation differed only as regards 1-VD patients (78 vs 40%).
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