Antinuclear antibody testing in obstetric patients.

OBJECTIVES: To assess possible associations between the presence of antinuclear antibodies (ANAs) and pregnancy outcome in order to determine the significance of this test in obstetric practice. METHODS: A case-control study was performed on 408 patients admitted to an obstetric high care unit and on whom ANA testing was consecutively performed. The study group consisted of 46 patients who tested positive for ANAs and a control group of 92 patients who tested negative for ANAs. In addition to demographic data, indications for admission and pregnancy outcome were compared between the two groups. RESULTS: Of the 46 patients with a positive ANA result, 28 had an antinuclear pattern, 13 an anticytoplasmic pattern and 5 an antinuclear and an anticytoplasmic pattern. No significant differences were observed between the two groups (ANA-positive and negative) with regard to demographic data, indication for admission, clinical and laboratory data, and pregnancy outcome. The patients were also tested for anticardiolipin antibodies, and significantly more patients with severe pre-eclampsia tested positive (24% versus 4.7%, p = 0.01). No difference in HIV status and presence of autoantibodies was found between the two groups. CONCLUSION: The presence of ANAs was not associated with adverse pregnancy outcome. Therefore routine patient testing for ANAs in an obstetric high-care unit is not recommended.

Measurement of plasma volume using 99Tc(m)-labelled DMP-HSA.

Red cell volume (RCV) and plasma volume (PV) measurements are performed routinely in nuclear medicine departments to diagnose a number of haematological disorders. Currently, 125I-HSA is used as a plasma tracer and 99Tcm-labelled red cells to determine red cell volume. 125I-HSA is not always readily available, leading to inconvenience for patients and medical practitioners. Due to the availability of 99Tcm in nuclear medicine departments, the use of albumin labelled with 99Tcm was investigated. A new 99Tcm-human serum albumin labelling kit (99Tcm-DMP-HSA) was developed by Verbeke and supplied for use in this study. The main aim of the study was to investigate the use of 99Tcm-DMP-HSA for PV determination. Secondly, the feasibility to determine red cell and plasma volume simultaneously using 99Tcm as radionuclide in both instances was investigated. Fourteen healthy volunteers were enrolled in the dual-phase study. During the first study, 99Tcm-DMP-HSA was used as tracer to calculate PV (PV1a) after intravenous administration. Subsequently, 99Tcm-labelled red cells were administered and the PV (PV1b) and RCV (RCV1) were calculated. The second study was repeated within 2 weeks using the conventional method. 125I-HSA and 99Tcm-labelled red cells were administered simultaneously. The PV (PV2) and RCV (RCV2) were calculated. We found that the redistribution of 99Tcm-DMP-HSA is faster than that of 125I-HSA; therefore, the plasma counts obtained at different times were back-extrapolated to time zero for plasma volume calculations. The mean values for the different calculated PVs were 2964+/-470 ml for PV1a, 3006+/-623 ml for PV1b and 3001+/-530 ml for PV2, the reference PV. The confidence intervals indicate no significant differences between plasma volumes PV1a and PV2 and plasma volumes PV1a and PV1b. The mean calculated RCV1 was 2130+/-322 ml; that of RCV2 was 2128+/-353 ml. The difference between RCV1 and RCV2 was not significant. Our results indicate that 99Tcm-DMP-HSA could be used for plasma volume calculation. Red cell and plasma volumes can be calculated simultaneously using 99Tcm as radionuclide in both cases.

Determination of the dosage of recombinant hirudin to inhibit arterial thrombosis in baboons.

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.

The effect of monoclonal anti-human-platelet antibodies on platelet kinetics in a baboon model: IgG subclass dependency.

We assessed the in vivo effect of six intact anti-human antiplatelet antibodies of two major IgG subclasses on platelet kinetics in baboons. Five of the six antibodies tested caused thrombocytopenia of varying degree when injected at a precalculated threshold value. An agglutinating IgG1 antibody (MA-8L4A12) caused a long-lasting, mild thrombocytopenia with a predominant uptake of radiolabelled platelets in the spleen, while the four IgG2 antibodies tested (MA-13G8E1, MA-2M5A6, MA-21K2E8 and MA-22M10) caused a severe, transient thrombocytopenia with uptake of platelets in the liver. Two of the IgG2 antibodies (MA-13G8E1 and MA-2M5A6) caused platelet activation and aggregation in vitro, whilst the other two did not elicit a platelet aggregation response. The platelet survival time was shortened with all five of the thrombocytopenia-inducing antibodies, while only one antibody (MA-2M5A6) had a significant effect on the bleeding time. This study indicates that the IgG subclasss may be a determining factor in the outcome of platelet sequestration in immune-induced thrombocytopenia.

Sites of elimination and pharmacokinetics of recombinant [131I]lepirudin in baboons.

Lepirudin has a short half-life, and only 50-60% of the intravenously administered dose is excreted by the kidneys. The fate of the remainder is unknown. We designed a study to determine the fate of this lepirudin. In each of six baboons, [131I]lepirudin was given intravenously as a bolus or infused over 30 min, 24 h apart. The in vivo redistribution of [131I]lepirudin was determined and quantified by scintillation camera imaging. In all studies, the half-life of [131I]lepirudin, as determined from the disappearance of radioactivity, was 21 +/- 3 min. The half-life determined from the disappearance of lepirudin, measured by the Ecarin Clotting Time (ECT) method, was similar at 23 +/- 8 min. Results obtained with the labeled lepirudin are therefore comparable with those obtained using the plasma concentration of lepirudin. When lepirudin was administered as a bolus, the half-life was 18 +/- 4 min, and lepirudin was cleared from the plasma at a rate of 42 +/- 12 mL/min and by the kidneys at 23 +/- 2 mL/min. Following infusion over 30 min, the half-life and total and renal clearances were not significantly different. In both studies, between 50 and 60% of the administered lepirudin was excreted by the kidney. Studies on sacrificed baboons showed that appreciable amounts of lepirudin were present in the bile, indicating the liver as a contributor to the elimination of lepirudin.

r-Hirudin inhibits platelet-dependent thrombosis during cardiopulmonary bypass in baboons.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Haematology outreach clinics in the Free State and northern Cape.

OBJECTIVE: Evaluation of haematology outreach clinics in the Northern Cape and Free State. DESIGN: Retrospective analysis of records from March 1994 to February 1996. SETTING: Central South Africa is sparsely populated. Consultants from Bloemfontein held outpatient clinics in hospitals (with laboratories) in Bethlehem, Kimberley and Kroonstad. SUBJECTS: 117 patients with suspected haematological disease. MAIN OUTCOME MEASURES: Input measures (population, number of clinics and costs), process measures (patient numbers, patients per clinic, new consultations per clinic, patients' domicile, how they were referred, types of diagnoses and number of patients with non-haematological disorders) and output measures (attrition, changes in attendance and savings). MAIN RESULTS: The 84 clinics that were held, with 636 consultations, did not cost the State anything. Only 6% of the 117 patients had no haematological problem. Sixty-eight per cent had chronic haematological neoplasms. In Kimberley most of the patients came from Kimberley Hospital, while most of the patients at the other clinics were referred via Bloemfontein. There was only a 10% attrition rate and only one-third of patients were referred to Bloemfontein. We saved paying patients an estimated R21,260 in transport costs, while saving the State R172,992 by seeing patients at secondary, instead of tertiary, hospitals. CONCLUSIONS: It is cheaper to send a doctor to an outreach clinic than to refer patients to a central facility, provided there is enough work for a doctor at the clinic. It costs the State much less for patients to be seen at a secondary than a tertiary hospital. Positive spin-offs include academic stimulation of doctors and laboratories in the periphery, with more appropriate referrals to teaching hospitals. Weaknesses include poor availability of expensive drugs at the clinics and lack of standardised records. By commuting to outreach clinics, specialists can greatly reduce health expenditure and spread it from tertiary to lower levels. At the same time more patients have access to their services.

Haemostatic profile of the San (Bushmen) relocated to Schmidtsdrif.

OBJECTIVE: To document the routine haemostatic variables of a group of San relocated from Namibia to South Africa. DESIGN: Cross-sectional study done in two stages. SETTING: Schmidtsdrif military camp in late 1990 and early 1991. SUBJECTS: Healthy adult San volunteers: 31 males and 54 females from the Vasakela and Barakwena groups in 1990; 135 males from the Vasakela group in 1991. The subjects were all soldiers or their dependants. MAIN OUTCOME MEASURES: The following tests were performed: activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen and coagulation factors V, VII, VIII, IX, X, XI and XII. The results were compared with a Western population reference group (N = 50). MAIN RESULTS: Almost all the haemostatic variables were statistically significantly lower than those of the reference group. The mean derived fibrinogen concentration in the plasma in the first stage of the study (1990) was significantly higher, but this reverted to normal during the second stage (1991), perhaps reflecting a general improvement in health. CONCLUSIONS: Even though the San are one of the best studied groups of indigenous people, this is the first published report on their haemostatic condition. The generally lower levels of haemostatic variables may reflect the lower prevalence of cardiovascular disease in the San. The population needs to be followed up as they westernise.

Plasma volume expansion with Haemaccel does not impair haemostasis during reduction mammaplasty.

OBJECTIVES: An in vivo study under well-controlled conditions was undertaken to determine the effect of Haemaccel, a colloidal plasma volume expander, on normal haemostasis. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: We could not find any scientific evidence that Haemaccel affects haemostasis; neither does it increase bleeding relative to Ringer's lactate.

Transient interruption of arterial thrombosis by inhibition of factor Xa results in long-term antithrombotic effects in baboons.

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% (p < 0.05) 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.

Immunoglobulin G sub-class concentrations in South African adults: ethnic differences and reference ranges.

Serum samples from healthy adult volunteers (n = 149) were selected at random from disputed paternity cases, laboratory staff and volunteers attending clinical trials. Total immunoglobulin G (IgG) and IgG sub-class (IgGSc) concentrations were determined by a radial immunodiffusion technique (RID). Standard statistical analyses were used to determine differences between groups. Reference ranges of IgGSc concentrations were calculated on the resultant groups of data. Total IgG and IgGSc concentrations in men and women of the same racial group were similar, except for IgG4 which was slightly higher in white males than in white females (median: 0.36 g/L vs 0.20 g/L respectively). IgGSc concentrations were higher in blacks than in whites (median values: IgG: 17.1 vs 12.1 g/L; IgG1: 11.1 vs 7.6 g/L; IgG2: 4.3 vs 3.2 g/L; IgG3: 1.2 vs 0.90 g/L respectively) with the exception of IgG4 which was similar in both groups (median: 0.29 g/L). It would appear that IgGSc values differ among the ethnic groups. Ethnicity must therefore be considered when calculating reference ranges. The reference ranges for the IgG sub-classes in the two ethnic groups are intended for use in our laboratory and in others in South Africa that use the RID technique.

The effect of r-hirudin vs. heparin on blood-membrane interactions during hemodialysis.

UNLABELLED: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A comparison between the use of recombinant hirudin and heparin during hemodialysis.

The purpose of this study was to determine the anticoagulant and antithrombotic potential of hirudin during hemodialysis by comparing the efficacy of dialysis with heparin to that of dialysis with recombinant hirudin (r-hirudin). Eleven patients with chronic renal failure and on maintenance hemodialysis were included in this open cross-over study. Conventional doses of heparin were administered during the first dialysis of the study. Two days later r-hirudin, at a dose of 0.15 mg/kg, was given as a bolus at the start of the second dialysis. The mean decreases in plasma levels of urea, uric acid and creatinine were approximately 50% after dialysis with both anticoagulants. Dialysis was therefore equally effective. However, effective dialysis with r-hirudin was achieved with a shorter activated partial thromboplastin time (APTT; range 65 to 103 seconds) compared to that with heparin (> 120 seconds), thereby decreasing the risk of bleeding. Markedly less 111In-labeled platelets accumulated at the inlet of the artificial kidney when r-hirudin was used, suggesting a smaller loss of hollow fiber volume. The results indicate that hirudin may be a suitable alternative anticoagulant for use during hemodialysis and it thus warrants further investigation.

Prolonged inhibition of acute arterial thrombosis by high dosing of a monoclonal anti-platelet glycoprotein IIb/IIIa antibody in a baboon model.

The in vivo activity of MA-16N7C2, the first monoclonal antibody that contains an echistatin-like RGD-sequence and inhibits platelet glycoprotein (GP)IIb/IIIa function, was determined in baboons. A dose-finding study assessing haemostatic variables such as bleeding time and ex vivo platelet aggregation showed that doses of as low as 0.2-0.3 mg/kg resulted in a pronounced effect. The effects were dose-dependent and lasted for several days, implying that MA-16N7C2 is a potent and long-acting GPIIb/IIIa inhibitor. Following the initial studies, the antithrombotic effect of 0.1 and 0.3 mg/kg of the antibody, given as a bolus, was determined in a baboon model of platelet-dependent, arterial-type thrombus formation. In these studies, a thrombogenic device consisting of Dacron vascular graft material was inserted as extension segments into a permanent arteriovenous shunt. The results confirmed the potent and long-lasting antithrombotic effect of MA-16N7C2. Surprisingly, the antithrombotic effect was stronger 48 h after a dose of 0.3 mg/kg administration than on the day of treatment with 0.1 mg/kg, despite the fact that comparable numbers of GPIIb/IIIa receptors were occupied on resting platelets. We postulate that with the high dose of MA-16N7C2 and after an extended period, occupied GPIIb/IIIa may be internalised by the platelets. Upon platelet activation, these receptors become reexposed but are unable to participate in thrombus formation. This is in contrast to unoccupied internal GPIIb/IIIa receptors early after a low dose of MA-16N7C2.

Multiple doses of trandolapril do not affect warfarin pharmacodynamics.

OBJECTIVE: The effects of multiple doses of trandolapril (a new angiotensin-converting enzyme inhibitor) on the pharmacodynamics of a single 25 mg dose of warfarin were investigated in 19 men. DESIGN: A double-blind, placebo-controlled cross-over design was used. The study consisted of two periods of 13 days each, during which subjects received either trandolapril 2 mg or placebo once daily according to a randomisation plan. Warfarin was given on day 8 of each of these periods. SETTING: The study was carried out at the Hoechst Research Centre for Clinical Pharmacology, Department of Pharmacology, University of the Orange Free State, Bloemfontein. PATIENTS: Nineteen healthy white men aged between 18 and 28 years and weighing between 65 and 98 kg volunteered for the study. OUTCOME MEASURES: Prothrombin time (PT) and coagulation factors II, VII, IX and X were measured before and sequentially up to 6 days after warfarin administration. Areas under the PT and coagulation factor time curves for warfarin + trandolapril were compared with the corresponding areas for warfarin + placebo. The two treatment combinations were also compared at each measuring time. RESULTS: The point estimate for the ratio of the treatment means of warfarin + trandolapril relative to warfarin + placebo for PT was 97% (90% confidence interval: 90%-103%). The corresponding value for factor VII was 97% (90% confidence interval: 91%-102%). CONCLUSION: The concomitant administration of trandolapril did not affect the pharmacodynamic effects of warfarin.

A four-hour infusion of recombinant hirudin results in long-term inhibition of arterial-type thrombosis in baboons.

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 (aPTT > 300 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)

Haematological condition of the San (Bushmen) relocated from Namibia to South Africa.

A cross-sectional study was undertaken to assess the haematological condition of the San (Bushmen) relocated from Namibia to South Africa. We studied 238 subjects--145 men and 93 women; none of the women was pregnant. We performed full blood counts and estimations of serum vitamin B12, folate, ferritin and erythrocyte folate concentrations. The mean haemoglobin concentration among the men was 14.7 g/dl and 19 (13%) were anaemic; among the women it was 13.8 g/dl and 18 (19%) were anaemic. Thirteen (9%) of the men and 22 (24%) of the women had low concentrations of serum ferritin, and 38 (26%) of the men and 22 (24%) of the women had erythrocyte folate concentrations of less than 270 nmol/l. Three (2%) men and 4 (4%) women had serum vitamin B12 concentrations of less than 120 pmol/l. Eighty-one (56%) of the men and 76 (82%) of the women had eosinophilia, probably because of parasitic infections. It would appear from this and previous studies that prolonged exposure of these hunter-gatherers to a Western lifestyle has resulted in a high prevalence of anaemia, caused by low iron and folate intakes, complicated by alcohol consumption.

Antithrombotic activity of Bay u3405, a thromboxane A2-antagonist, in patients with Dacron aortic grafts: a random controlled clinical trial.

Twelve patients with Dacron aortic grafts participated in a placebo controlled, crossover trial to investigate the effect of Bay u3405, a thromboxane A2 receptor antagonist, on graft thrombogenicity. During each treatment period (seven days, Bay u3405 or placebo), 111In-platelet survival and platelet deposition on the grafts were measured daily by gamma-camera imaging and blood radioactivity analysis. Bay u3405 substantially reduced the deposition of platelets and the thrombogenic index, while platelet survival remained unchanged. The ex vivo platelet aggregation response to ADP and epinephrine was significantly inhibited. The bleeding time increased slightly but not to any clinically relevant extent, and no adverse side effects were recorded. Bay u3405 seems to be a safe and effective drug for the inhibition of platelet deposition on aortic Dacron grafts. The use of quantitative imaging techniques is also more sensitive than the measurement of platelet survival for the assessment of antiplatelet drug efficacy in patients with aortic grafts.