THE EFFECT OF INTRAVENOUS IMMUNOGLOBULIN ON PLATELET KINETICS IN CHRONIC IMMUNE THROMBOCYTOPAENIC PURPURA (ITP)

1987 ◽  
Author(s):  
P N Badenhorst ◽  
H F Kotze ◽  
A duP Heyns ◽  
M G Lotter ◽  
P Wessels ◽  
...  
Keyword(s):  
Intravenous Immunoglobulin ◽  
Kinetic Studies ◽  
Ivig Therapy ◽  
Reticuloendothelial System ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Significant Difference ◽  
Before And After ◽  
High Doses

Most patients with ITP respond to high doses of intravenous immunoglobulin (IVIg) with a transient increase in platelet count. The effect of IVIg on platelet kinetics was studied in 5 patients with chronic ITP. Autologous platelets were labelled with In-111 and mean platelet lifespan (MPLS) calculated; in vivo distribution and sites of platelet sequestration were determined with a scintillation camera and computer assisted image analysis. The studies were performed before and after treatment with 2 g/kg Sandoglobulin. Two groups of patients were identified: those with a splenic platelet sequestration pattern (spleen-liver In-111-activity ratio >1.4) and those with diffuse sequestration of platelets in the reticuloendothelial system (RES).There was a significant difference in mean platelet counts before and after treatment (p<0.05). Patients with a splenic sequestration pattern responded better to IVIg: the MPLS lengthened and the high spleen-liver ratio decreased. In the diffuse RES sequestration pattern group, IVIg had almost no effect on platelet kinetics. We conclude that platelet kinetic studies identify a subgroup of patients with ITP who will respond to IVIg therapy.

scholarly journals Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr- labeled platelets differ

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 86-92 ◽  
Author(s):  
P Heyns A du ◽  
PN Badenhorst ◽  
MG Lotter ◽  
H Pieters ◽  
P Wessels ◽  
...  
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Severe Disease ◽  
Reticuloendothelial System ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Antiplatelet Antibody ◽  
Thrombocytopenic Purpura ◽  
Computer Assisted Image ◽  
The Difference

Abstract Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr- labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.

Kinetics, Redistribution And Fate Of Indium-111-Labelled-Platelets In Patients With Aortic Aneurysms

1981 ◽  
Author(s):  
A duP Heyns ◽  
M G Lötter ◽  
P N Badenhorst ◽  
F de Kock ◽  
H Pieters ◽  
...  
Keyword(s):  
Imaging System ◽  
Reticuloendothelial System ◽  
Aortic Aneurysms ◽  
Whole Body ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Normal Limits ◽  
Geometrical Mean ◽  
Indium 111

Platelets of 7 patients with abdominal aortic aneurysms were labelled with In-lll-oxine prior to surgery. The platelets were reinjected with the patient positioned under a scintillation camera with a computer assisted imaging system. Images were acquisitioned daily, areas of interest selected with the computer, organ radioactivity- quantitated with a geometrical mean method and expressed as a percentage of whole body radioactivity. Platelet survival (PS) in the circulation was determined, and disappearance curves fitted to a gamma function “multiple hit” model.Mean PS was shorthened to 143,2 ± 47h (normal 232<17); the dissappearance curves were exponential in all but the two patients who had PS within normal limits. The surgically removed aneurysms were dissected and radioactivity of different layers measured. In-111-activity was confined to the superficial layers of the aneurysm.These techniques allow quantitative studies of the in vivo distribution of labelled platelets. Platelets are deposited in the aneurysms, this shortens PS, the disappearance curves become exponential, and the major sites of deposition of In-111-activity are in the liver and spleen. This indicates that although platelets are damaged and deposited in the aneurysm, the reticuloendothelial system remains a major site of platelet sequestration.

Kinetics And Sites Of Destruction Of Indium-111-Oxine Labelled Platelets In Immune Thrombocytopenic Purpura

1981 ◽  
Author(s):  
A duP Heyns ◽  
P N Badenhorst ◽  
M G Lötter ◽  
F de Kock ◽  
C Herbst ◽  
...  
Keyword(s):  
Imaging System ◽  
Kinetic Studies ◽  
Reticuloendothelial System ◽  
Whole Body ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Thrombocytopenic Purpura ◽  
Indium 111 ◽  
System Acquisition ◽  
In Parenthesis

Kinetics and quantification of the sites of destruction of In-111-oxine labelled autologous platelets was investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 9 × 109/l; platelets were separated by differential centrifugation and labelled with 5,6 ±2,5 MBq In-111. Whole body and organ In-111-platelet distribution was quantitated with a scintillation camera and a computer assisted imaging system acquisition matrix. Areas of interest were selected with the computer and organ In-111-radioactivity expressed as a percentage of whole body activity. Mean platelet survival was 49,5+29,6h, and the survival curves exponential. Equilibrium percentage organ In-111-radioactivity was (normal values in parenthesis): spleen 33,7±8,8 (31,1 ± 10,2); liver 16,1 ± 9,5 (13,1 ± 1,3); thorax 22,8 ± 3,7 (28,8 ± 5,6). Percentage organ In-111-activity at the time when labelled platelets had been removed from the circulation was: spleen 44,5 ± 16,4 (40 ± 16); liver 16,0 ± 11,5 (32,4 ± 7,2); thorax 19,7±6,0 (17,7 ± 10,3). Thorax activity corresponds to radioactivity in the bony cage of the thorax. Three patterns of platelet sequestration were evident. Three patients had mainly splenic sequestration; two, mainly hepatic sequestration; and three, diffuse reticuloendothelial system sequestration with a major component of platelets destroyed in the bone marrow. Splenectomy was performed in two patients. The pattern of In-111-platelet sequestration was not predictive of response to glucocorticoid therapy or indicative of the necessity for splenectomy. Quantitative In-111-labelled autologous platelet kinetic studies provide a new tool for the investigation of platelet disorders.

scholarly journals Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr- labeled platelets differ

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 86-92
Author(s):  
P Heyns A du ◽  
PN Badenhorst ◽  
MG Lotter ◽  
H Pieters ◽  
P Wessels ◽  
...  
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Severe Disease ◽  
Reticuloendothelial System ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Antiplatelet Antibody ◽  
Thrombocytopenic Purpura ◽  
Computer Assisted Image ◽  
The Difference

Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr- labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.

scholarly journals Decrease in Platelet Aggregability after Total Oophorectomy

1977 ◽  
Author(s):  
H. Yamazaki ◽  
T. Motomiya ◽  
M. Sonoda ◽  
N. Miyagawa
Keyword(s):  
Platelet Count ◽  
Clinical Evidence ◽  
Coulter Counter ◽  
Control Group ◽  
Bilateral Oophorectomy ◽  
Platelet Volume ◽  
Platelet Aggregability ◽  
Significant Difference ◽  
Before And After

Substantial clinical evidence indicates that large doses of estrogen frequenly result in thromboembolic disorders. Effects of estrogen on platelet aggregability were examined in women with uterine myoma before and after oophorectomy. Bilateral oophorectomy on 15 cases (48.7+0.12 yrs, mean+SE) and unilateral or no oophorectomy on 18 cases (control group : 42.2+0.18 yrs) were performed with myomectomy of the uterus. On one day before and one day, one week and one month after the operation performed, their platelet count by Coulter counter, platelet volume by Coulter channelyzer and platelet aggregability by Sienco aggregometer were measured. 24 hrs total estrogen in urine was also determined. In the control group, platelet counts were 85.1+ 4.9 % of the preoperated value one day after, 127.9+9.0 % one week after and 98.1+7.6 % one month after the operation. In the bilateral oophorectomy group, these were 82.4+5.2 % one day after, 124.0+4.7 % one week after and 96.1+4.8 % one month after. Both the groups showed the same change. Platelet aggregability by 3 μM ADP were 76.9+14.3 % one day after, 203.0+57.1 % one week after and 193.4+59.0 % one month after in the control, while 55.0+13.6 % one day after, 102.5+12.9 % one week after and 60.6+14.7 % one month after the operation in the total oophorectomy group. There was a statistically significant difference in the values obtained one month after the operation between the groups (p<0.05). Characteristic changes in platelet volumes were also observed. A significant correlation was observed between the platelet aggre-gabilities and the daily urinary estrogen excretion levels. The above results suggest that estrogen may enhance platelet aggregability in vivo.

RES hyperphagocytosis by rats with streptozotocin-induced diabetes mellitus

1981 ◽  
Vol 240 (3) ◽  
pp. G225-G231
Author(s):  
R. P. Cornell
Keyword(s):  
Body Weight ◽  
Insulin Dose ◽  
Reticuloendothelial System ◽  
Diabetic Rats ◽  
Phagocytic Index ◽  
Control Value ◽  
Colloidal Carbon ◽  
Significant Difference

In contrast to previous studies of neutrophils from diabetic animals and humans in vitro and of macrophages from diabetic humans in vivo, which reported phagocytic depression, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon was observed in rats at 14 and 28 days after diabetes induction with streptozotocin (STZ). Carbon clearance half times were significantly enhanced to 6.3 +/- 0.79 and 8.1 +/- 1.04 min at 14 and 28 days post-STZ, respectively, compared with the nondiabetic value (12.7 +/- 0.98 min). The severity of uncontrolled STZ-induced diabetes in rats was confirmed by significant hypoinsulinemia, hyperglucagonemia, hyperglycemia, and hyperlipidemia. Although body weights of STZ-diabetic animals declined progressively, liver weights as a percent of body weight increased above the control value at 14 and 28 days post-STZ. In fact, expression of carbon phagocytosis as the corrected phagocytic index, which accounts for changes in liver and spleen weights relative to body weight, eliminated the significant difference between STZ-diabetic and nondiabetic animals. Antibiotic treatment of diabetic rats failed to alter the hyperphagocytosis, implying that a chronic bacterial infection was not the cause of phagocytic stimulation. Daily insulin replacements, but not a single large insulin dose to 14-day post-STZ rats, reversed the enhanced phagocytosis of colloidal carbon.

3D culture model and computer-assisted videomicroscopy to analyze migratory behavior of noninvasive and invasive bronchial epithelial cells

2005 ◽  
Vol 289 (6) ◽  
pp. C1547-C1552 ◽  
Author(s):  
Salma Hazgui ◽  
Noël Bonnet ◽  
Jérôme Cutrona ◽  
Béatrice Nawrocki-Raby ◽  
Myriam Polette ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Line ◽  
3D Model ◽  
Migratory Behavior ◽  
Computer Assisted ◽  
Data Set ◽  
Significant Difference ◽  
Kinetics Of ◽  
Invasive Cell

To date, most of the studies in the field of cell migration have been applied to two-dimensional (2D) models. To mimic the three-dimensional (3D) conditions similar to those observed in vivo during tumor invasion, we developed a 3D model of cell migration in which cells were embedded in a collagen I matrix placed in a double-compartment chamber. Using time-lapse videomicroscopy and interactive cell tracking in a four-dimensional data set, we determined the cell trajectories and their migration kinetics. We compared the 2D and 3D migratory behavior of a noninvasive cell line (16HBE) with the migratory behavior of an invasive cell line (BZR). Our results show that the 3D migration kinetics of the noninvasive cell line were lower than the migration kinetics of the invasive cell line. In contrast, in 2D models, no significant difference was observed between the two cell lines. To validate our 3D model, we further investigated the effect of epidermal growth factor (EGF), a promoter of tumor cell motility and invasion on the noninvasive cell line (16HBE). EGF increased significantly the migration kinetics of the noninvasive cell line. Our results show that the 3D model of cell migration allowed us to differentiate the migratory behavior of invasive and noninvasive cells and that such a model can help in the development of molecular targeted therapy as it approaches the in vivo conditions.

Effect of Single Dose In Vivo Propranolol Therapy on In Vitro Adhesion of Human SS RBC.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1234-1234 ◽  
Author(s):  
Laura M. De Castro ◽  
Jude C. Jonassaint ◽  
Jennifer G. Johnson ◽  
Milena Batchvarova ◽  
Marilyn J. Telen
Keyword(s):  
Safety Data ◽  
Study Drug ◽  
Flow Chamber ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Number Of Patients ◽  
Significant Difference ◽  
Before And After

Abstract Sickle red blood cells (SS RBC) are abnormally adhesive to both endothelial cells (ECs) and components of the extracellular matrix (ECM). Epinephrine (epi) has been shown to elevate cAMP in SS RBC and increase adhesion of SS RBC to ECs in a protein kinase A-dependent manner. In vitro and in vivo studies performed in our lab have led to the hypothesis that adrenergic stimuli such as epi may initiate or exacerbate vaso-occlusion and thus contribute to the association of vaso-occlusive events with physiologic stress. We are conducting a prospective, dose-escalation pilot clinical study to investigate whether in vivo administration of one dose of propranolol either down-regulates baseline SS RBC adhesion in vitro or prevents its upregulation by epi. In addition, this study will provide additional safety data regarding the use of propranolol in normotensive patients with sickle cell disease (SCD). Figure Figure To date, we have completed the first two dose cohorts. 11 subjects (9 SS and 1 Sβ° thalassemia; 7 females, 3 males) have participated. No severe adverse events were noted. Cohorts 1 and 2 had mean pre-propranolol blood pressure (BP) of 116 (5.9 SD)/ 60.4 (3.98 SD) and 106.8 (4.68 SD)/ 58 (3.9 SD), respectively; this difference was not statistically significant. Minimal and asymptomatic changes in BP were noted in both cohorts after drug administration, with biphasic systolic and diastolic BP nadirs at 45 and 240 minutes. No clinically significant changes in heart rate were observed. Adhesion studies were performed using a graduated height flow chamber on the day of RBC collection. RBC adhesion to ECs was studied before and after epi stimulation and was measured at sheer stresses ranging from 1 to 3 dyne/cm2. Baseline adhesion measurements were validated by comparing percent (%) adhesion assayed at 2 different times within 7 days—at screening and before propranolol dose on the study drug day. We observed no significant difference in adhesion at the 2 different time points without propranolol. Comparison of % adhesion of epi-stimulated RBC to ECs before and 1 hour after propranolol showed that propranolol given in vivo significantly inhibited both non-stimulated and epi-stimulated SS RBC adhesion (p=0.04 and p=0.001, respectively). Lastly, comparison of SS RBC adhesion at both drug doses confirmed the drug-related inhibition of adhesion (p&lt;0.004). We conclude that propranolol administered in vivo decreases SS RBC baseline adhesion to ECs and substantially abrogates epi-stimulated adhesion to ECs, as measured in vitro. Although we have thus far studied only a small number of patients and low propranolol doses, we expect to confirm these results with the 3rd cohort, in which a higher dose of propranolol will be used. If our findings continue to show that propranolol can decrease both SS RBC baseline and epi-stimulated adhesion to ECs, study of propranolol on a larger scale would be warranted in order to ascertain its safety and efficacy as an anti-adhesive therapy in SCD.

Influence of changes in arterial pCO2 on cerebral blood flow and metabolism during high-dose barbiturate therapy in dogs

1981 ◽  
Vol 54 (5) ◽  
pp. 615-619 ◽  
Author(s):  
Neal F. Kassell ◽  
Patrick W. Hitchon ◽  
Mary K. Gerk ◽  
Martin D. Sokoll ◽  
Todd R. Hill
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
High Dose ◽  
Sodium Thiopental ◽  
Arterial Pco2 ◽  
Content Type ◽  
Cerebral Vasoconstriction ◽  
Significant Difference ◽  
Before And After ◽  
High Doses

✓ In 13 dogs the response of the cerebral circulation to changes in PaCO2 ranging from 20 to 60 torr was studied before and after administration of high doses of sodium thiopental. Infusion of sufficient barbiturate to produce 30- to 60-second burst suppression in the electroencephalogram was associated with a profound degree of cerebral vasoconstriction, equivalent to that produced by hypocapnia with PaCO2 = 20 torr. Furthermore, once sodium thiopental was administered, no significant difference in cerebral blood flow (CBF) or vascular resistance (CVR) was noted between PaCO2 of 30 and 20 torr. However, changes of approximately 15% in CBF and 30% in CVR were noted between PaCO2 at 40 and 20 torr. These data suggest that hyperventilation of PaCO2 of less than 30 torr may not effectively increase the degree of cerebral vasoconstriction in these circumstances.

Kinetics and in Vivo Redistribution of 111Indium-Labelled Human Platelets after Intravenous Protamine Sulphate

1980 ◽  
Vol 44 (02) ◽  
pp. 065-068 ◽  
Author(s):  
A duP Heyns ◽  
M G Lötter ◽  
P N Badenhorst ◽  
H Kotze ◽  
F C Killian ◽  
...  
Keyword(s):  
Imaging System ◽  
Human Platelets ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Protamine Sulphate ◽  
Normal Volunteers ◽  
Activated Platelets ◽  
Platelet Survival ◽  
Platelet Aggregates

SummaryThe pathogenesis of thrombocytopenia induced by intravenous protamine sulphate was studied in six patients who underwent cardiopulmonary bypass surgery, and in three normal volunteers. Autologous platelets were labelled with 111Indium-oxine. Platelet lifespan was determined. In vivo 111In-platelet localization, organ redistribution and sites of destruction were quantitated with a scintillation camera and a computer-assisted imaging system. Protamine induced a transient thrombocytopenia, maximal 5-10 min after injection, and 30-40 min in duration. The thrombocytopenia was accompanied by a transient accumulation of platelets in the liver. The splenic platelet pool remained unaltered and no platelets accumulated in the lungs. Platelet survival, measured in two volunteers, was slightly longer than normal and fitted a linear function best. There was a severe transient neutropenia during the period of thrombocytopenia. We conclude that protamineinduced thrombocytopenia is caused by hepatic accumulation of "activated" platelets or platelet aggregates, the process is reversible, and in the two normal volunteers studied, platelet survival was not affected.

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