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Biomedical subjects

A D Heyns

Publications and source records attributed to A D Heyns.

At least 37 records · Page 2Linked to original sources
PubMed1989

Thromboembolic potential of synthetic vascular grafts in baboons.

We have compared in baboons the capacity of two types of synthetic vascular grafts to accumulate thrombus, activate circulating platelets, and generate occlusive platelet microemboli. Grafts were incorporated into femoral arterial-arterial shunts placed unilaterally in 10 baboons; the unoperated contralateral limbs served as controls. The accumulation of indium 111 (111In)-labeled platelets onto the grafts (expanded polytetrafluoroethylene [ePTFE] or knitted Dacron, 4 mm inner diameter) and the appearance of 111In radioactivity in distal microcirculatory beds (calf and foot) were quantified by dynamic scintillation camera imaging. After 1 hour total platelet deposition per graft was higher with Dacron (49.0 +/- 8.0 x 10(9) platelets) than with ePTFE (3.7 +/- 0.6 x 10(9) platelets, p less than 0.01). Platelet counts decreased and beta-thromboglobulin levels increased with Dacron graft placement but were unaffected by ePTFE graft placement (p less than 0.05 and p less than 0.01, respectively). Emboli shed from Dacron grafts were detected as multifocal, irregular, and changing deposits in the calves and feet. Indium 111 platelet activity in the feet distal to the Dacron grafts increased 81.1% +/- 21.4% from baseline values over 1 hour, whereas the activities in the feet distal to the ePTFE grafts were unchanged (p less than 0.05). The increase 111In-platelet radioactivity above the control limb values (excess radioactivity) was higher for the Dacron graft group than for the ePTFE group in both the feet (139.6% +/- 46.9% vs 6.2%, p less than 0.05) and the calves (86.7% +/- 21.7% vs 7.3% +/- 3.6%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

A computer program in compiled BASIC for the IBM personal computer to calculate the mean platelet survival time with the multiple-hit and weighted mean methods.

We developed an easy-to-operate computer program for the IBM personal computer to calculate, display and store in a database platelet kinetic data determined by analysis of the rate of clearance of radiolabeled blood platelets from the circulation. This was done by curve fitting using the weighted mean method and multiple-hit model. These models are complementary and calculating the mean platelet survival time with both is recommended. Improvement of the weighted mean method was investigated. The optimized weighting and fitting the exponential function with the Marquardt non-linear least squares method improved the weighted mean method. The weighted mean and multiple-hit models fit the survival curve data equally well. The calculation of the mean platelet survival time with the weighted mean method was very fast. The duration of calculation with the multiple-hit model could take up to 2 minutes. Calculation of the mean platelet survival time using both models has the advantage that conditions when calculation of the mean platelet survival time would be invalid, can be detected. The computer program will promote the valid comparison of results obtained at different institutions.

Blood Platelets↗
PubMed1987

Kinetics and in vivo distribution of in-111-labelled platelets and platelet function in familial hypercholesterolaemia.

The kinetics, in vivo distribution and sites of sequestration of autologous In-111-labelled platelets and other platelet function parameters were studied in ten patients with type IIa or IIb familial hypercholesterolaemia and thrombotic complications of atherosclerosis. The in vitro platelet aggregation response to ADP (P = 0.50) and collagen (P = 0.46); binding of fibrinogen to platelets (P = 0.61); and plasma beta-thromboglobulin levels (P = 0.42) of the patients and normal reference subjects did not differ significantly. The in vivo distribution of In-111-labelled platelets at equilibrium was within normal limits, and at the end of platelet life-span the sequestration pattern of labelled platelets in the reticuloendothelial system was also normal (spleen P = 0.31; liver P = 0.54). There was minimal evidence of in vivo platelet activation: only mean platelet lifespan (MPLS), 195 +/- 57 hours (difference between mean MPLS of patients and controls was 25 hours, with a 95% confidence interval from 23 to 31 hours; P = 0.02); mean platelet platelet turnover, 2298 +/- 824 platelets/microliter/hour (P = 0.005); plasma platelet factor 4 (P = 0.02); and the mean circulating platelet aggregate ratio, 0.8 +/- 0.1 (P = 0.02); differed significantly from normal. These results suggest that abnormalities of platelet function and kinetics observed in type II hyperlipoproteinaemia cannot be ascribed wholly to the hyperlipidaemia, but may be induced by the associated atherosclerosis.

Adult↗
PubMed1987

A formula for correcting for the in vitro release of platelet beta-thromboglobulin.

The interpretation of platelet beta-thromboglobulin (BTG) and platelet factor 4 (PF4) levels as indicators of in vivo platelet activation is complicated by the artefactual release of these proteins in vitro. A formula was devised to correct for in vitro platelet activation and release of BTG. Blood was collected from normal volunteers by an ideal method and BTG and PF4 levels determined by radioimmunoassay; these were the reference values. Blood from normal volunteers was activated in vitro by standing at room temperature. The BTG and PF4 released was measured at different time intervals. The relationship between BTG and PF4 released was measured at different time intervals. The relationship between BTG and PF4 was measured mathematically best described by a second degree polynomial function. The true plasma BTG value was then calculated by correcting for in vitro release by the general formula: BTG corrected = BTG measured - BtG for PF4 measured + BtG for PF4 reference The validity of the correction formula was tested in 10 normal subjects and in patients with either recent myocardial infarction(n = 10), familial hypercholesterolaemia(n = 10) or arterial prostheses(n = 14). Correction was adequate in normal subjects if the plasma BTG levels did not exceed 260ng/ml. In patients with a thrombotic tendency, the formula overcorrected for in vitro release. This could be ascribed to increased in vivo PF4 levels in these patients, especially those with prostheses. The reference values for PF4 in these patients, and especially those with vascular prostheses, were also higher than normal. The PF4 measured in their plasma thus reflects both in vivo and in vitro released protein. The hypothesis on which the correction formula was based, is therefore not always applicable. It may be possible to improve the correction by establishing formulae for specific disease groups.

Adult↗
PubMed1987

111In-labelled baboon platelets: the influence of in vivo redistribution and contaminating 114mIn on the radiation dose.

In five normal baboons, whole body 111In decreased slowly (t1/2 = 60 days) after the end of platelet lifespan. There was slight elution of radioactivity from the liver and spleen, the important sites of platelet sequestration. A fraction of this eluted radioactivity accumulated in the bone marrow, but also in other tissues. This redistribution did not have a significant effect on the measurement of in vivo platelet kinetics. It did however, diminish the total weighted radiation dose, especially that due to contaminating 114mIn.

Animals↗
PubMed1987

Ultrastructural morphometric observations on serial sectioned human blood platelet subpopulations.

The relationships between the volume of human platelets and their cytoplasmic organelles were studied by morphometric analysis. Platelets were separated into four density-dependent subpopulations on an arabino-galactan gradient. In vitro activation of platelets was effectively prevented by maintaining them at a constant ambient temperature of 37 degrees C. Serial sections were cut through platelets, morphometrically analyzed and the platelets reconstructed. The volumes of the individual platelets and their constituent granules, mitochondria and open canalicular systems (OCS) were calculated. Individual organelles were counted. The mean volumes of the platelets of the subpopulations decreased significantly as density decreased (p = 0.01). Also, as the density of platelets decreased, there was a decrease in the mean unit volume of their granules (p = 0.003). In contrast, independent of platelet volume or density, the OCS occupies about 10% of the platelet volume. These findings indicate that it is possible to prevent in vitro platelet activation by maintaining their environment at 37 degrees C. Our study confirms the direct relationships between platelet volume and density; and platelet density and granule content. There is no ready explanation for the constant relationship between platelet volume and that of the OCS.

Blood Platelets↗
PubMed1986

Evidence that 111In-labelled platelets pool in the spleen, but not in the liver of normal humans and baboons.

The kinetics of pooling of platelets in the spleen may be used to measure spleen function. However, pooling of platelets in other organs, especially the liver, may affect these kinetic measurements. We have therefore compared, in man and baboon, the kinetics of 111In-labelled platelets and 111In-labelled red cells in the liver and spleen during the first 60 min after reinjection. This was determined in vivo with a scintillation camera and computer-assisted image analysis. Organ radioactivity was expressed as a percentage of that of the whole body. In both humans and baboons, the spleen accumulated many more platelets than red cells. Also, the red cells equilibrated more rapidly. The presence of a splenic platelet pool was thus confirmed. In contrast, the percentages of labelled platelets and labelled red cells in the liver were similar in both species. In both species, the sum total of labelled platelets in the circulation, i.e. recovery, and that quantified in the spleen at equilibrium, were equal to approximately 100%. These results confirm the presence of the exchangeable splenic platelet pool, and indicate that there are no significant exchangeable platelet pools in either the liver or any other organs.

Animals↗
PubMed1986

Evaluation of mathematic models to assess platelet kinetics.

Twelve mathematic methods used to calculate the mean platelet survival time were compared by determining the "goodness of fit" of the models to the platelet survival curves of 15 reference subjects and 54 patients. Platelets were labeled with [111In]oxine. The linear (LN), exponential, weighted mean, multiple hit (MH), Dornhorst (DH), Meuleman (ML), alpha order (AO), and polynomial (PO) mathematic models were investigated. The goodness of fit for the exponential model was determined by the nonlinear least squares method (EP), and also by the linear least squares method on logarithmically transformed data (EX) as is recommended. The modified weighted mean (MWM) and the usual weighted mean method (WM) obtained with these exponential models were tested. The Dornhorst (DH10) and Meuleman (ML10) models, where the potential age-dependent platelet survival times were kept constant at 10 days, were also evaluated. The goodness of fit results, expressed as % s.d. indicated that the LN (5.2%), EX (5.0%), EP (4.4%), WM (3.7%), DH10 (3.7%), and ML10 (3.7%) models all fitted the data significantly worse than the MWM, MH, DH, ML, AO, and PO models (range 3.2-3.3%). The mean platelet survival time determined with the MH model differed significantly from the results with the DH, ML, and AO models. The results of mean platelet survival time calculated with different mathematic models cannot, therefore, be compared directly. The models that fitted the platelet survival curve well varied slightly in sensitivity to noise as is indicated by the coefficient of variation of the mean platelet survival time estimates for the reference subjects (range 7.9-12.0%). Fitting data to at least two mathematic models has definite advantages. Data on which the calculations are based are probably invalid if the following are true: (a) if the mean platelet survival time estimated with the alpha order model is shorter than that estimated with the EP, MWM, or MH models, or (b) the mean platelet survival time estimated with either the DH, ML, AO, or PO models, is longer than the LN, MWM, or MH estimate of the mean platelet survival time. We conclude that the mean platelet survival time can be reliably estimated by fitting the data to either the MWM method (if limited computing facilities are available) or the MH model. Confidence in the result will be increased if considered in conjunction with the finding obtained with one other model; in those cases where the platelet survival time is very short, the alpha order model is recommended.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Platelets↗
PubMed1985

Kinetics of In-111-platelets in the baboon: I. Isolation and labelling of a viable and representative platelet population.

A fully representative and viable platelet population was isolated from the blood of 15 baboons by a multiwash procedure, and labelled with In-111-oxine. The recovery of the total platelet population in the circulation was 85% +/- 9. Mean platelet life span was 146 hr +/- 13. Correcting for plasma radioactivity (always less than 3.5%) did not significantly affect the estimate of platelet life span (145 hr +/- 16) or recovery (85% +/- 12). Platelet survival estimates, repeated at different times, were reproducible. In 5 baboons, platelets were also harvested by a single step differential centrifugation. The mean life span of a representative platelet population was significantly longer than that of platelets harvested by a single step. Recovery values of the representative and non-representative population were similar. We conclude that it may be important to harvest and label a fully representative platelet population for kinetic studies. The proposed method is simple and reproducible, and may be applied in studies in humans.

Animals↗
PubMed1985

Kinetics of In-111-platelets in the baboon: II. In vitro distribution and sites of sequestration.

The kinetics and sites of sequestration of a fully representative population of In-111-platelets were determined in 11 baboons. The in vivo method of quantification with computer assisted scintillation camera image analysis was validated by sacrificing 5 baboons and measuring and comparing the distribution of organ radioactivity. Recovery of platelets in the circulation was 87% +/- 7, and their mean survival time was 147 hr +/- 15. The mean splenic platelet pool was 16.0 +/- 1.9. At equilibrium 15.8% +/- 2.9 of the In-111-platelets were in the hepatic blood pool. Senescent platelets were destroyed in the reticulo-endothelial system. The major sites of sequestration were: liver (37.6% +/- 6.0), and the spleen (23.3% +/- 4.6). The bone marrow sequestrated 14.4% +/- 1.7 of the labelled platelets, and 15.5% +/- 4.0 were present in various other tissues. We conclude that the in vivo method of In-111-quantification is accurate. Senescent platelets are mainly sequestrated in the reticuloendothelial tissue, with the liver, spleen and the bone marrow important sites of sequestration.

Animals↗
PubMed1985

An improved method for the quantification of the in vivo kinetics of a representative population of 111In-labelled human platelets.

The recommended and commonly used methods for the isolation of platelets from whole blood do not harvest a representative platelet population. There is evidence that these methods may result in the loss of a functionally more active platelet subpopulation. We describe a method whereby a completely representative population of platelets was isolated from the whole blood of 28 normal human volunteers by repeated washing of platelets from the red-cell layer. The harvesting efficiency was 98.3% +/- 2.8%. The platelets were labelled with 111In-oxine in a saline milieu with a labelling efficiency of 86.4% +/- 6.8%. The disappearance of reinjected labelled autologous platelets from the circulation was almost linear, and the mean platelet survival was estimated to be 224 +/- 23 h. At equilibrium, 61% +/- 12% of the labelled platelets were recovered from the circulation. The in vivo distribution at equilibrium and the sites of sequestration of the senescent labelled platelets were determined by geometric-mean whole-body quantification in six of the volunteers. This improved method permits accurate quantification of organ 111In radioactivity. Following reinjection, the labelled platelets pooled in the spleen and the accumulated activity can be presented by a single exponential function. At equilibrium, 31.1% +/- 6.1% and 9.6% +/- 1.2% of the platelets were in the spleen and liver, respectively. Splenic and hepatic radioactivity increased significantly with time, and at the end of the platelet life span, 35.6% +/- 9.7% and 28.7% +/- 8.3% of the labelled platelets were sequestrated in these organs, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

The antiproliferative effect of interferon and the mitogenic activity of growth factors are independent cell cycle events. Studies with vascular smooth muscle cells and endothelial cells.

We studied the antagonistic effects of interferon (IFN) and growth factors in G0/G1-arrested normal bovine aortic smooth muscle cells (SMC) which were stimulated by serum, or purified platelet derived growth factor (PDGF), supplemented with plasma-derived serum (PDS). The growth response, measured as [3H]thymidine incorporation into DNA, was dependent on the concentration of the mitogen. Human IFN alpha, recombinant human IFN alpha 2, or a crude bovine-IFN preparation prepared from virus-infected bovine aortic endothelial cells, inhibited SMC growth induced by either serum or PDGF with PDS. The extent of IFN inhibition was inversely related to the concentration of the mitogenic stimulus. We also investigated whether IFN inhibited the early events in G1 phase, stimulated by the competence factor PDGF, or the progression of the cell into the S phase induced by PDS. The results indicated that IFN inhibited these two stages of the G1 phase independently. In addition, we investigated the antiproliferative effect of IFN on bovine aortic endothelial cells (BAEC), which do not respond to PDGF but to the mitogenic activity of fibroblast growth factor (FGF). IFN inhibited the mitogenic activity of FGF in a dose-dependent manner. The results indicate that the anti-proliferative activity of IFN and the mitogenic effects of different growth factors are independent.

Animals↗
PubMed1985

Kinetics, distribution, and sites of destruction of indium-111 oxine labelled red cells in haemolytic anaemia.

The survival of red cells labelled with indium-111 oxine in the circulation was determined. In vivo distribution at equilibrium and sites of deposition at the T50In--that is, the half life of labelled red cells--were quantitated with a scintillation camera and computer assisted image analysis. Although the rate of elution. Of 111In from the red cells was higher than that of chromium-51-disodium chromate, estimates of T50In and T50Cr corresponded reasonably well and were shortened in haemolytic anaemia. In normal subjects red cells were sequestered mainly in the liver and spleen. In five patients with different types of haemolytic anaemia two distinct patterns of red cell sequestration could be recognised: mainly splenic sequestration, and destruction of red cells in the liver, spleen, and the bone marrow. These patterns were expected for the particular disease studied.

Adolescent↗
PubMed1983

Haematological reference values for the Basotho.

Haematological reference values for a defined population of healthy adult Basotho are presented, with appropriate statistical treatment of the data. The well-documented apparent neutropenia in Blacks was observed, as well as the apparent sex difference as regards lymphocytes. The importance of adequate health criteria is stressed, 42% of apparently normal females having low serum ferritin levels. This could lead to an error of 1 g/dl in the haemoglobin level at the lower limit of the reference value. Only 34% of the apparently healthy females met all the criteria for health.

Adolescent↗
PubMed1983

Fanconi's anemia: a cytogenetic study on lymphocyte and bone marrow cultures utilizing 1,2:3,4-diepoxybutane.

Fanconi's anemia (FA) is an autosomal recessive genetic trait characterized by congenital abnormalities, pancytopenia with a late onset, and increased chromosome instability. A great deal of heterogeneity exists in the disease, making an early correct diagnosis very difficult. Previously chromosome instability was used as a diagnostic tool but was found to be unreliable. Auerbach et al. have described the use of a difunctional alkylating agent, 1,2:3,4-diepoxybutane (DEB), in lymphocyte, fibroblast, and amniotic fluid cultures for the accurate diagnosis of homozygotes and heterozygotes for the FA gene. We report here the findings on lymphocyte and bone marrow cultures from 18 FA homozygotes and 17 family members. Statistical analysis of the results with DEB at different concentrations showed a significant increase in induced chromosome breakage rates for homozygotes and heterozygotes when compared to those for a control group. The bone marrow cultures gave similar results.

Anemia, Aplastic↗