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The purpose of this article is, firstly, to demonstrate the application of some methodological fieldwork principles to a restricted sociolinguistic survey undertaken in a semi-urban speech community in KwaZulu-Natal. Secondly, it will be indicated that the structured nature of language variation is revealed by such an investigation even at a low level of methodological sophistication. An interesting conclusion to be drawn from the survey is that the direction of language change can be shown at this level, something which is normally only possible when employing the parameter of style variation.

Lexicographers compiling translating dictionaries are not exclusively concerned with semantic equivalence when selecting translating equivalents for lemmata, but often include also grammatical information in illustrative examples when the lexical item to be translated does not have an exact grammatical counterpart in the target language. This is especially so in the case of typologically divergent languages, of which Afrikaans and Zulu are representative examples in the South African context. In the application of translation theory to lexicographic practice, it seems sensible to decide in favour of a descriptive approach (Toury 1990), which, in contrast to the prescriptive approach, does not assume an ideal relation between source text and target text, but in fact examines the relation between the two texts (which correlates in the case of a translating dictionary respectively with lemma and translating equivalent) in an empirical way. In this article, the problem of grammatical disparity between lemma and translating equivalent in a learners' dictionary involving the above-mentioned languages is considered. Not only disparity relating to syntactic categories, but also the morphological status of lemmata (as words, and as sub- and multilexical items) are covered in the investigation of the data. As a consequence of the insights thus gained into the systematic nature of this asymmetric relation, suggestions are made to utilise the format of the microstructure as a means to convey grammatical facts of the target language to the learner.Keywords: afrikaans, grammatical equivalence, learners' dictionaries, lexicography, macrostructure, microstructure, morphology, syntax, translating dictionaries, translation theory, trilingual dictionaries, zulu

Cultured human umbilical cord endothelial cells are mostly used to study the response of endothelium to various stimuli. The effect of the culture process on cell function is however, not known and the function of endothelial cells from different anatomical loci differs. In view of this we developed a flow chamber to study the function of fresh endothelium. The flow chamber was designed to accommodate a five cm piece of baboon aorta in a closed circuit where six hours of perfusion of the aorta with Ringer’s lactate/dextrose buffer at 37 °C was maintained by a peristaltic pump.

Cultured human umbilical cord endothelial cells are mostly used to study the response of endothelium to various stimuli. The effect of the culture process on cell function is however, not known and the function of endothelial cells from different anatomical loci differs. In view of this we developed a flow chamber to study the function of fresh endothelium. The flow chamber was designed to accommodate a five cm piece of baboon aorta in a closed circuit where six hours of perfusion of the aorta with Ringer’s lactate/dextrose buffer at 37 °C was maintained by a peristaltic pump.

SummaryPlatelets were isolated from blood of baboons and treated with neuraminidase to remove platelet membrane sialic acid, a process which artificially ages the platelets. The platelets were then labelled with 111In and their mean life span, in vivo distribution and sites of Sequestration were measured. The effect of removal of sialic acid on the attachment of immunoglobulin to platelets were investigated and related to the Sequestration of the platelets by the spleen, liver, and bone marrow. Removal of sialic acid by neuraminidase did not affect the aggregation of platelets by agonists in vitro, nor their sites of Sequestration. The removal of 0.51 (median, range 0.01 to 2.10) nmol sialic acid/108 platelets shortened their life span by 75 h (median, range 0 to 132) h (n = 19, p

N-Trimethyl chitosan chloride (TMC; high molecular weight) and N-trimethyl chitosan oligosaccharide (TMO; low molecular weight) with different degrees of quaternisation were synthesised and evaluated for their absorption enhancing properties across mucosal epithelia. These quaternised chitosan derivatives (0.0625% w/v-0.5% w/v) showed a significant decrease in the transepithelial electrical resistance (TEER) of cultured rabbit tracheal epithelial cell monolayers as compared to the control. The degree of quaternisation and concentration of the compounds influenced the extent of the reduction in TEER. Higher degrees of quaternisation and an increase in the concentration of the compound were associated with a more pronounced reduction in the TEER. The TMO derivatives seemed to be more effective in lowering the TEER of tracheal cell monolayers as compared to the TMC polymers. Ciliary beat frequency (CBF) is the main defence mechanism of the respiratory tract and is therefore a useful parameter in evaluating the toxicity of nasally administered drugs and additives. The effect of the synthesised chitosan derivatives on the CBF of human nasal epithelial cells at pH 7.4 was determined by a method based on an analogue contrast enhancement technique. The TMO oligomers exhibited lower inhibition of the CBF of human nasal epithelial cells compared to that of the TMC polymers. It was proposed that this reduced effect on the CBF is due to the lower viscosity and molecular weight of TMO. However, no acute toxicity was found with any of the synthesised chitosan derivatives by means of the CBF tests conducted in this study.

For a better understanding of the behaviour of macromolecules in vitro and in vivo, their structural and chemical properties that may be influential as experimental variables need to be characterised. N-Trimethyl chitosan chloride and N-triethyl chitosan chloride have been synthesised from chitosan to increase the solubility range of these polymers. However, little is known about the effect of the degree of quaternisation, molecular weight, viscosity and different substitution groups on the polymer's ability to enhance the transport of large hydrophilic compounds, such as peptide and protein drugs, across intestinal and nasal epithelia and on their toxicity profile. This study describes the synthesis of various quaternised chitosan polymers from low and medium molecular weight chitosan. These polymers were characterised to determine if any relationships between their degree of quaternisation, molecular weight and viscosity could be found which will determine their behaviour as absorption enhancers in future studies.

The intranasal toxicity of selected absorption enhancers (LPC, DM beta CD, N-trimethyl chitosan chloride (TMC) and chitosan hydrochloride) were determined in vivo by investigating the acute microscopic toxic potential on the morphology of rat nasal epithelium with transmission electron microscopy (TEM) and in vitro by measurement of the ciliary beat frequency (CBF), of human ciliated nasal epithelium. TEM evaluations showed that LPC (1% w/v) caused severe epithelial damage and pyknosis. No damage to the rat nasal epithelium was caused by the other absorption enhancers. CBF measurements showed that LPC resulted in total loss of ciliated cells while DM beta CD, TMC and chitosan hydrochloride did not cause any major changes in CBF.

Recombinant hirudin, a potent and direct inhibitor of thrombin, effectively inhibits platelet-dependent thrombosis. Our aim was to establish the plasma concentration at which r-hirudin expresses its optimal antithrombotic effect. We measured the extent of inhibition of (111)In-labeled platelet deposition onto 0.6 cm(2) segments of Dacron vascular grafts. These grafts were incorporated as extension segments into exteriorized permanent femoral arteriovenous shunts in baboons. In six control studies a mean of 1.99 +/- 0.26 x 10(9) platelets were deposited at the end of 120 min. In the treatment studies, a thrombus was allowed to form for 10 min in six animals. Treatment for 30 min with r-hirudin at dosages of 140, 70, and 35 microgram/kg/min, but not 14 microgram/kg/min, dose dependently interrupted platelet deposition. The relationship between the percent inhibition of platelet deposition caused by r-hirudin and the plasma concentration of hirudin was exponential (i.e., % Inhibition = 95(1-e(0.23 x [r-hirudin])) (R(2) = 0.76). From this, we estimated that 50% inhibition of platelet deposition will occur at a plasma concentration of approximately 3.3 microgram r-hirudin/mL and 80% at 8.1 microgram/mL. The relationship between the inhibition of platelet deposition and the plasma concentration of hirudin makes it possible to estimate the dose of hirudin that will result in a given level of inhibition of platelet deposition.

An understanding of the role that ethnicity in conjunction with language played in the shaping of South African society is offen obfuscated by the stigmatization of concepts as a result of the country's political history. In this article, an attempt is made to view the corollaries ofsocial engineering within the objective framework of Haugen 's ecology of language and to understand the ways in which social, cultural, and linguistic factors interacted both as a result of and in spite ofpolicies aimed at manipulating the formation of communities in this country. Some ofthese corollaries are (1) the formation of communities sharing a common language, but by law divided along ethnic (read "racial") lines; (2) the formation by law of communities on the basis of linguistic differences, but with a common ethnic affiliationj ancestry; (3) the formation ofkoines and creole varieties; (4) purism and shifts in language loyalty; and (5) contradictory views on the Status and function of the mother tongue. A prognosis of future developments is made, given the multilingual nature, andhence heterogenous ethnolinguistic composition, of South African society. Two opposing forces are at work, viz. an increasing awareness of the necessity to revalorize the indigenous languages, and a strong tendency to select an erstwhile colonial language, English, as lingua franca. The author submits that the outcome of this new struggle will have a profound effect on the linguistic and sociocultural future of the country.

Systemic anticoagulation is required during cardiopulmonary bypass (CPB) to inhibit the activation of platelets, the coagulation system and ultimately thrombus formation. Unfractionated heparin is most commonly used, but it is neither entirely safe nor completely effective. The use of protamine sulphate to reverse the anticoagulant effect further complicates the use of heparin. The clinical need for a heparin substitute is therefore obvious. We evaluated the efficacy of r-Hirudin, a potent and specific inhibitor of thrombin, as anticoagulant in a baboon model of cardiopulmonary bypass.Ten baboons, divided into two groups of five each, were used. The one group received 0.7 mg/kg r-Hirudin as a bolus before CPB was started, followed by a constant infusion of 1.4 mg/kg/hr for the 90 min of CPB. The other group received a bolus of 2.5 mg/kg heparin before the start of CPB, followed by maintenance dosages to maintain the activated clotting time (ACT)400 sec.Adequate anticoagulation was obtained with both anticoagulants. Haemodilution due to priming the extracorporeal system with Ringer's lactate and appropriately anticoagulated donor blood, was equivalent in both groups. During CPB with heparin, but not with hirudin, there was a significant increase in the number of circulating platelet aggregates, thrombin-antithrombin (TAT) complexes and 111In-labelled platelet accumulation in the oxygenator. After the initial decrease in platelet count due to haemodilution, it further decreased significantly during CPB with heparin but remained relatively constant when r-Hirudin was used.Our results strongly suggest that r-Hirudin is superior to heparin especially with respect to its inhibitory effect on platelet dependent thrombogenesis caused by the biomembranes of the oxygenator.

An in vivo study under well-controlled conditions was undertaken to determine the effect of Haemaccel, a colloidal plasma volume expander, on normal haemostasis.Twenty patients, who were admitted for reduction mammaplasty, were included in this study. A standardised anaesthesia protocol was followed with all patients. Ten patients received 500 ml Haemaccel and 10 controls received 1,500 ml Ringer's lactate, a crystalloid solution. The solutions were administered intravenously during surgery over a period of 30-40 minutes. Standardised clinical observations and haematological tests were done at the following time intervals: after anaesthesia but before infusion of the plasma substitute, immediately after infusion was completed, and 20, 40 and 60 minutes after infusion.The blood pressure, pulse rate and O2 saturation levels were not influenced by the treatment given. Haemodilution was similar for the two patient groups. The platelet count and plasma levels of fibrinogen decreased in parallel with haemodilution. Thereafter the platelet count gradually increased to pre-infusion counts at 60 minutes. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT) and platelet aggregation in response to adenosine diphosphate (ADP) and collagen were not affected by the plasma volume expander given. Arachidonic acid-induced aggregation decreased significantly after Ringer's lactate was given but did not change when Haemaccel was given. The bleeding time was prolonged slightly, but not significantly, from 7.4 +/- 1.6 minutes to 8.8 +/- 1.6 minutes with Ringer's lactate and from 6.9 +/- 2.0 to 9.7 +/- 3.7 minutes with Haemaccel.We could not find any scientific evidence that Haemaccel affects haemostasis; neither does it increase bleeding relative to Ringer's lactate.

The aim of this study was to determine if recombinant (r-)hirudin, used as anticoagulant during hemodialysis, has favourable effects on blood-membrane interactions. The results were compared with that obtained when standard unfractionated heparin, the anticoagulant of choice, was used.Eleven patients with chronic renal failure and on maintenance hemodialysis were included in this open cross-over study. Heparin was administered according to the existing protocol in use at the Dialysis Unit during the first dialysis of the study (5,000 to 10,000 IU). r-Hirudin, 0.15 mg/kg, was given as a bolus at the start of the second dialysis, two days later. The effect of the anticoagulant on leukocyte and complement activation, thrombogenesis, release of platelet activating factor and pulmonary gas exchange was studied.In most cases after dialysis with heparin (8 of 11), but not with r-hirudin, macroscopically visible thrombi formed at the inlet of the artificial kidneys. Irrespective of the anticoagulant used, a transient leukopenia (neutropenia) developed ten minutes after dialysis was started. Heparin anticoagulation resulted in a significant increase in plasma levels of complement C3a at all time points, whereas with r-hirudin the increase was significant after only 30 and 240 min. The O2 saturation decreased significantly during the first two hours of dialysis with heparin. The partial O2 pressure decreased significantly during the first two hours of dialysis, irrespective of the anticoagulant used.We conclude that r-hirudin is superior to heparin with regard to inhibition of thrombus formation in the dialyzer during hemodialysis. Slight, but favourable effects on complement activation. O2 saturation and lung CO diffusing capacity were also found with r-hirudin.

Previous studies have established that chitosan hydrochloride and glutamate are potent absorption enhancers for large hydrophilic compounds across mucosal surfaces. However, these compounds lack solubility at neutral pH values. A partially quaternized and well-soluble derivative of chitosan, N-trimethyl chitosan chloride, was synthesized and the effects of this polymer on the transepithelial electrical resistance and permeability of intestinal epithelial cells were investigated in vitro.N-trimethyl chitosan chloride was synthesized by reductive methylation and characterized with NMR. The effect of this polymer (1.0-2.5% w/v) on the transepithelial electrical resistance of intestinal epithelial cells, using Caco-2 cell monolayers, was investigated. Permeation of the hydrophilic model compounds [14C]-mannitol (MW 182.2), FITC-Dextran (MW 4400) and the peptide drug buserelin (MW 1299.5), in the presence of N-trimethyl chitosan chloride (1.5-2.5% w/v), was followed for 3 hours. The transport process of the fluorescent marker, FITC-Dextran 4400, across the cell monolayers was visualised with confocal laser scanning microscopy. Viability of the cells was checked with the trypan blue exclusion technique.N-trimethyl chitosan chloride was found to be a perfectly water-soluble, partially quaternized (about 12%) derivative of chitosan. This polymer (1.5-2.5% w/v) caused a pronounced and immediate reduction (25-85%) in the transepithelial electrical resistance of Caco-2 cells. Large increases in the transport rate of [14C]-mannitol (32-60 fold), FITC-Dextran 4400 (167-373 fold) and buserelin (28-73 fold) were demonstrated. Confocal laser scanning microscopy confirmed that N-trimethyl chitosan chloride opens the tight junctions of intestinal epithelial cells to allow increased transport of hydrophilic compounds through the paracellular transport pathway. No deleterious effects to the cells could be demonstrated with trypan blue.The potential use of N-trimethyl chitosan chloride as an absorption enhancer across mucosal surfaces could be an important contribution towards the development of effective delivery systems for hydrophilic drugs.

Recombinant tick anticoagulant peptide (r-TAP) is a potent and specific inhibitor of activated coagulation factor X which effectively interrupts in vivo arterial thrombosis during treatment. It is, however, uncertain if it also affects thrombosis after treatment is stopped. This was tested in a baboon model of arterial thrombosis where platelet deposition onto Dacron vascular graft segments, inserted as extensions into permanent femoral arteriovenous shunts, was measured. The baboons were intravenously treated with 10 micrograms/kg/min (low dose, aPTT = 39 +/- 1 s) and 25 micrograms/kg/min (high dose, aPTT = 58 +/- 2 s) r-TAP for two hours. During treatment the r-TAP inhibited thrombin formation and dose-dependently interrupted platelet deposition onto the graft segment. This effect lasted for up to two hours after treatment with the low dose. Following treatment with the high dose, the graft segments were kept in place for 53 h. After treatment was stopped, platelets again deposited, but at a much lower rate than in control studies. Maximum deposition was approximately 38% lower than in the control studies. Total platelet deposition over 55 h, calculated as the area under the deposition curve, was approximately 40% (p0.05) less than in the control studies. A significant shortening in the mean platelet life span and an approximately 15-fold increase in thrombin-antithrombin III complexes during the first 31 h indicated that the thrombus surface remained thrombogenic and that the effect of r-TAP was transient. We have shown that 2 h of treatment with a full antithrombotic dose of r-TAP markedly reduced both the rate of platelet deposition after treatment was stopped and the total number of platelets deposited over 55 h. This was in spite of the finding that the antithrombotic effect of r-TAP was transient.

Intravenous recombinant (r)-hirudin has a potent antithrombotic effect in aspirin- and heparin-resistant platelet-dependent thrombus formation in baboon models. However, these thrombi reform when therapy is stopped after 60 minutes. To determine if 4 hours of therapy can produce a lasting antithrombotic effect, we investigated the extent of deposition of 111In-labeled platelets onto 0.5-cm2 segments of Dacron vascular grafts for 53 hours. These grafts had been incorporated into exteriorized permanent femoral arteriovenous shunts in baboons. Platelet deposition in eight untreated animals was generally sigmoidal. Maximum platelet deposition, 1.7% +/- 0.9% of injected labeled platelets, was reached after approximately 4 hours. Deposition then gradually decreased to 0.4% +/- 0.2% of injected labeled platelets after 53 hours. After a thrombus was allowed to form for 15 minutes in six animals, intravenous treatment with r-hirudin at a dose of 20 nmol (0.14 mg)/kg-min-1 (aPTT300 seconds) was started and maintained for 4 hours. Platelet deposition was interrupted during treatment. After infusion was stopped, platelets accumulated again, but not as much as in the untreated animals. Maximum platelet deposition, 0.7% +/- 0.2% of injected labeled platelets, was significantly less (P.01), and was reached after approximately 23 hours. Thereafter, deposition decreased to 0.4% +/- 0.2% at 53 hours. The shunts in all of the untreated animals occluded at some stage during the study, while only one shunt occluded in the treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Bay U3405 is a thromboxane A2 (TxA2)-receptor antagonist that inhibits the binding of TxA2 to its target cells. The aim of this study was to determine if Bay U3405 could be used to inhibit arterial thrombosis. A thrombogenic device, consisting of uncrimped Dacron vascular graft material (0.5 cm2) built into the wall of silicone rubber tubing with 4 mm inside diameter, was exposed to native flowing blood under arterial blood flow conditions (100-140 ml/min) by interposing the devices as extension segments into permanent femoral arteriovenous shunts implanted in baboons. Thrombus formation was quantified in vivo by measuring the deposition of 111In-labelled platelets onto the graft material with a scintillation camera. In six baboons, a bolus injection of Bay U3405, calculated to attain an initial plasma concentration of 300 ng/ml, reduced the maximum thrombus formation measured over a 2 h study period. Platelet deposition was reduced by 33 +/- 14% (SD) at 2 h as compared to control studies done in the same baboons. The accumulation of additional platelets onto a thrombus that was allowed to form for 1 h, was reduced by 58 +/- 28% at 2 h. Ex vivo platelet aggregation in response to ADP, activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) were not affected by the treatment. Ex vivo platelet aggregation in response to collagen was markedly inhibited for 2 h after treatment. The results demonstrated that selective blocking of the TxA2-receptor on platelets reduced platelet-dependent thrombus formation and the accumulation of additional platelets in a freshly formed thrombus.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study investigated the effects on self-concept of Rational-Emotive Therapy and auditory subliminal stimulation (separately and in combination) on 141 undergraduate students with self-concept problems. They were randomly assigned to one of four groups receiving either Rational-Emotive Therapy, subliminal stimulation, both, or a placebo treatment. Rational-Emotive Therapy significantly improved scores on all the dependent measures (cognition, self-concept, self-esteem, anxiety), except for behavior. Results for the subliminal stimulation group were similar to those of the placebo treatment except for a significant self-concept improvement and a decline in self-concept related irrational cognitions. The combined treatment yielded results similar to those of Rational-Emotive Therapy, with tentative indications of continued improvement in irrational cognitions and self-concept from posttest to follow-up.

In patients with arterial grafts, platelet consumption may be due either to platelet interaction with the graft, and/or concomitant platelet consumption in the rest of the arterial tree. This hypothesis was tested by quantifying the kinetics and platelet-graft interaction of indium-111-labelled platelets with double velour Dacron grafts in 13 patients with arterial insufficiency ascribed to atherosclerosis. Mean platelet lifespan (MPLS), 149 +/- 46 hours, was significantly shorter (P = 0.001) than normal. Labelled platelets were transiently deposited onto the graft surfaces. Peak 111In deposition on the grafts, 1.33 +/- 1.02% of injected labelled platelets, was reached at 70 +/- 33 hours. Thereafter the graft-platelet radioactivity decreased in parallel with platelet radioactivity in the circulation. There was no statistical correlation between MPLS and the factors known to be associated with graft platelet deposition: graft size; peak graft radioactivity; and the time to attain peak graft radioactivity. It is therefore concluded that in patients with arterial disease requiring graft implantation, the observed increased platelet consumption cannot only be ascribed to the interaction of platelets with the graft. Concomitant atherosclerosis is probably the important modifier of platelet consumption. The significant contribution of this factor to the shortening of the MPLS should be taken into account when assessing, by measuring platelet lifespan, the thrombogenicity of grafts.

The effect of the chelates oxine and tropolone, used to label platelets, on the kinetics of indium-111-(111In) labeled platelets was studied in twelve normal human subjects. Autologous platelets were labeled either in saline with 111In-oxine or in plasma with 111In-tropolone. Mean platelet lifespan was estimated by fitting the disappearance curve of platelets from the circulation to the multiple hit and other mathematical models. The in vivo distribution of platelets was quantitatively imaged with a scintillation camera. The in vivo recovery of 111In-oxine and 111In-tropolone did not differ, and the mean platelet lifespan was also similar (111In-oxine: 230 +/- 29 hr; 111In-tropolone: 226 +/- 13 hr). At equilibrium (90 min after reinjection of labeled platelets) and at the end of platelet lifespan, 111In-oxine and 111In-tropolone radioactivities in the spleen and liver were similar. These results demonstrate that the results of kinetics measured with 111In-oxine or 111In-tropolone do not differ significantly.

The present study was designed to investigate the possible effect of auditory subliminal stimulation on GSR. 38 undergraduate students were exposed subliminally to emotional words while GSR was monitored. The results confirmed the hypothesis that auditory subliminal stimulation would effect a significant increase in GSR.

To quantitatively characterize processes of platelet thrombus formation in vivo, the kinetics and incorporation into thrombus of autologous In-111-labeled platelets were compared in six patients with aortic aneurysms and in seven patients with prosthetic aortic grafts. Although platelet survival was comparably shortened in both patient groups (mean, 5.8 days), the maximum radioactivity (percentage of whole body radioactivity) as determined by gamma camera imaging was higher in the aneurysms than in the grafts (3.3% +/- 1.6% vs. 1.6% +/- 1.1%, p = 0.05). Maximum In-111 uptake was also attained more quickly in the aneurysm patients (2.3 +/- 0.8 days vs. 3.5 +/- 1.3 days; p = 0.07). The experimental platelet kinetic and imaging data were subsequently evaluated by compartmental analysis to estimate both normal and disease-related components of platelet destruction. This analysis indicated that deposited platelet radioactivity had a longer residence time on grafts (2.9 +/- 1.7 days vs. 1.4 +/- 0.9 days, p = 0.07) but accumulated at a faster rate in aneurysms (5.0% +/- 3.4% per day vs. 1.4% +/- 0.9% per day, p = 0.02). As determined by imaging, only a proportion of increased platelet destruction was specifically due to the aneurysms (55% +/- 38%) or grafts (17% +/- 11%, p = 0.03). This result indicates additional components of platelet destruction unrelated to graft and aneurysm thrombus formation which, in some graft patients, may reflect a greater severity of vascular disease or other mechanisms causing a preferential shortening of platelet survival. Thus, the analytical approach described may be a useful one for discriminating components of in vivo platelet utilization including platelet removal due to normal hemostatic and senescent mechanisms, localized thrombus formation, and more generalized vascular disease.

The relative sensitivities for the various in vivo and in vitro tests for platelet activation are unknown. This was studied in a baboon model where limited and more substantial injury to the vascular endothelium was inflicted. The endothelium of a segment of the right carotid artery was removed with a balloon catheter on day 0 (limited de-endothelialisation), and that of the left carotid artery, abdominal aorta and left femoral artery on day 7 (substantial de-endothelialisation). Eight baboons (Papio ursinus) were used. Baseline tests for platelet activation (platelet volume, platelet density, platelet aggregate ratio, and platelet and plasma levels of platelet factor 4 [PF4] and beta-thromboglobulin [beta-TG]) were performed 7 days before de-endothelialisation and repeated on days 1, 9 and 16. The kinetics of indium-111-labelled platelets were measured after substantial de-endothelialisation. Sham operations were done on 3 animals exactly as in the test, except that the balloon injuries were not inflicted. No influence on the results of the platelet function tests was found. The only test capable of detecting limited injury to the endothelium was the measurement of plasma PF4. The mean platelet life-span (MPLS) shortened, mean platelet density decreased, the circulating platelet aggregate ratio decreased, and plasma levels of PF4 and beta-TG increased (P less than 0.05 in all instances) after the substantial endothelial injury. The mean platelet volume, intraplatelet PF4 and beta-TG, and the in vivo distribution and sites of sequestration of labelled platelets were poor tests for in vivo platelet activation.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

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.

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.

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.