Nanoscale conductive pattern of the homoepitaxial AlGaN/GaN transistor.

The gallium nitride (GaN)-based buffer/barrier mode of growth and morphology, the transistor electrical response (25-310 °C) and the nanoscale pattern of a homoepitaxial AlGaN/GaN high electron mobility transistor (HEMT) have been investigated at the micro and nanoscale. The low channel sheet resistance and the enhanced heat dissipation allow a highly conductive HEMT transistor (Ids > 1 A mm(-1)) to be defined (0.5 A mm(-1) at 300 °C). The vertical breakdown voltage has been determined to be ∼850 V with the vertical drain-bulk (or gate-bulk) current following the hopping mechanism, with an activation energy of 350 meV. The conductive atomic force microscopy nanoscale current pattern does not unequivocally follow the molecular beam epitaxy AlGaN/GaN morphology but it suggests that the FS-GaN substrate presents a series of preferential conductive spots (conductive patches). Both the estimated patches density and the apparent random distribution appear to correlate with the edge-pit dislocations observed via cathodoluminescence. The sub-surface edge-pit dislocations originating in the FS-GaN substrate result in barrier height inhomogeneity within the HEMT Schottky gate producing a subthreshold current.

Dissecting the loci controlling fetal haemoglobin production on chromosomes 11p and 6q by the regressive approach.

The changes in the type of haemoglobin (Hb) produced during embryonic, fetal and adult life, have served as a paradigm for understanding the developmental regulation of human genes. A genetically determined persistence of fetal Hb synthesis has an ameliorating effect on beta thalassaemia and sickle cell anaemia, globally the commonest single gene disorders. The search for the putative gene(s) controlling the level of fetal Hb production has been extremely difficult because this trait may be influenced by several factors. We have studied a large kindred with hereditary persistence of fetal haemoglobin (HPFH). Using a genetic mapping strategy and statistical methods that account simultaneously for the effects of several genetic factors, we have demonstrated that in addition to the two factors (beta thalassaemia and Xmn I-G gamma site) on chromosome 11p, there is a third major genetic determinant for fetal Hb production localized on chromosome 6q.

Nanoscale investigation of AlGaN/GaN-on-Si high electron mobility transistors.

AlGaN/GaN HEMTs are devices which are strongly influenced by surface properties such as donor states, roughness or any kind of inhomogeneity. The electron gas is only a few nanometers away from the surface and the transistor forward and reverse currents are considerably affected by any variation of surface property within the atomic scale. Consequently, we have used the technique known as conductive AFM (CAFM) to perform electrical characterization at the nanoscale. The AlGaN/GaN HEMT ohmic (drain and source) and Schottky (gate) contacts were investigated by the CAFM technique. The estimated area of these highly conductive pillars (each of them of approximately 20-50 nm radius) represents around 5% of the total contact area. Analogously, the reverse leakage of the gate Schottky contact at the nanoscale seems to correlate somehow with the topography of the narrow AlGaN barrier regions producing larger currents.

Interaction of malaria with a common form of severe thalassemia in an Asian population.

In many Asian populations, the commonest form of severe thalassemia results from the coinheritance of HbE and beta thalassemia. The management of this disease is particularly difficult because of its extreme clinical diversity; although some genetic and adaptive factors have been identified as phenotypic modifiers, the reasons remain unclear. Because the role of the environment in the course of severe thalassemia has been neglected completely and because malaria due to both Plasmodium falciparum and Plasmodium vivax has been prevalent in Sri Lanka, we carried out a pilot study of patients with HbE beta thalassemia that showed high frequencies of antibodies to both parasite species and that 28.6% of the children had DNA-based evidence of current infection with P. vivax. Malarial antibodies then were assessed in patients with HbE beta thalassemia compared with those in age-matched controls. There was a significant increase in the frequency of antibodies in the thalassemic patients, particularly against P. vivax and in young children. There was also a higher frequency in those who had been splenectomized compared with those with intact spleens, although in the latter it was still higher than that in the controls. The thalassemic patients showed significant correlations between malaria antibody status and phenotype. Patients with HbE beta thalassemia may be more prone to malaria, particularly P. vivax, which is reflected in their clinical severity. Because P. vivax malaria is widespread in Asia, further studies of its interaction with HbE beta thalassemia and related diseases are required urgently as a part of ongoing thalassemia control programs.

Preparedness to Respond to Family Violence: A Cross-Sectional Study Across Clinical Areas.

Introduction: Family violence (FV) is one of the most urgent health issues of our generation. While nurses play a vital role in identifying and supporting victim/survivors of violence, little is known about nursing readiness to respond across clinical areas. Objective: This study aimed to compare and contrast the knowledge, confidence, clinical skills, and perceived barriers of nurses across three clinical areas of a tertiary trauma hospital in Melbourne, Australia, in responding to FV. Method: A prospective, mixed methods design was used. The nursing staff at a large trauma hospital were approached to participate. Participants completed a brief online survey to quantify clinician-reported knowledge, clinical skills, and barriers to managing FV. Results: Two hundred and forty-two nursing staff electronically completed a brief survey to capture self-reported confidence, knowledge, clinical skills, and barriers to working effectively in the area. The descriptive analysis reflected service-wide deficits in knowledge, confidence, and self-reported clinical skills, irrespective of the work area. Deficits were identified on a background of limited structured training for FV among this cohort. Significantly higher rates of FV confidence and knowledge were identified among emergency department nurses relative to acute and subacute clinical counterparts. Conclusion: Nurse respondents overall reported low rates of confidence, knowledge, and clinical skills in responding to disclosures of FV. Findings reinforce the need for imbedded training programs to support frontline responses.

Jean Langlais (1907-91): an historical case of a blind organist with stroke-induced aphasia and Braille alexia but without amusia.

The subject of a prior report of a blind organist with aphasia and Braille alexia without amusia, published in French, has been identified as Jean Langlais. His artistic and medical history is presented, the latter via translation of the original 1987 paper.

Haemoglobin E beta thalassaemia in Sri Lanka.

Haemoglobin E beta thalassaemia is the commonest form of severe thalassaemia in many Asian countries, but little is known about its natural history, the reasons for clinical diversity, or its management. We studied 109 Sri Lankan patients with the disorder over 5 years. 25 patients were not receiving transfusion; transfusion was stopped with no deleterious effect in a further 37. We identified several genetic and environmental factors that might contribute to the phenotypic diversity of the disorder, including modifiers of haemoglobin F production, malaria, and age-related changes in adaptive function. Our findings suggest that haemoglobin E beta thalassaemia can be managed without transfusion in many patients, even with low haemoglobin levels. Age-related changes in the pattern of adaptation to anaemia suggest that different and more cost-effective approaches to management should be explored.

Effect of high dose aspirin on coronary hemodynamics during pacing-induced myocardial ischemia.

The effects of aspirin on coronary hemodynamics and transcardiac concentrations of thromboxane B2 (the stable metabolite of thromboxane A2) were determined at rest and during pacing-induced myocardial ischemia in 11 patients with coronary disease. Control coronary sinus pacing increased both arterial thromboxane B2 (331 +/- 70 to 623 +/- 132 pg/ml, p less than 0.02) and coronary sinus thromboxane B2 (184 +/- 3 to 403 +/- 156 pg/ml, p less than 0.05), but positive transmyocardial gradients developed in only three patients. After 650 mg of oral aspirin, more than 90% inhibition of in vitro thromboxane B2 production was demonstrated and circulating thromboxane B2 was undetectable at rest and during pacing in all patients. Despite these changes in thromboxane B2 concentrations, coronary blood flow was unchanged by aspirin at rest (107 +/- 14 versus 112 +/- 13 ml/min, p = NS) and during pacing (189 +/- 29 versus 181 +/- 25 ml/min, p = NS). Myocardial lactate extraction was also unchanged at rest (24 +/- 7 versus 19 +/- 5%, p = NS) and during pacing (5 +/- 6 versus 9 +/- 5%, p = NS). No change occurred in the anginal threshold. Thus, aspirin does not have the vasoconstrictive properties that have been reported with another cyclo-oxygenase inhibitor, indomethacin. These findings also suggest that thromboxane A2 production does not play a major role in the pathogenesis of stress-induced ischemia. Nonetheless, intracoronary thromboxane A2 production in some patients may potentiate platelet activation and coronary thrombosis. Such patients may benefit from long-term aspirin therapy and can be treated with aspirin without risk of adverse coronary hemodynamic effects.

Platelet factor 4 mRNA expression in human erythroleukemic cells: regulation by phorbol esters and certain cytokines.

Developing megakaryocytes are distinguished from progenitor cells by the appearance of platelet proteins such as platelet factor 4 (PF 4). The human erythroleukemic cell line HEL can also be induced to produce PF 4 by incubation in phorbol esters. HEL cells were used here as a model system in which to study the phenomenon of inducible PF 4 production at both the mRNA and protein levels. The cytokines interleukin 1 beta (IL-1 beta), interleukin 3 (IL-3), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (EPO), and transforming growth factor-beta (TGF-beta) were also evaluated for their effects on PF 4 mRNA induction in HEL cells.

The effects of the fiber components pectin, cellulose and lignin on serum cholesterol levels.

Eight-week randomized cross-over studies in three separate groups of 10 healthy volunteers were undertaken to determine the effects of daily dietary supplementation with pectin (12 g/day), cellulose (15 g/day) and lignin (12 g/day) on serum lipid levels. Detailed dietary records were kept throughout the study and there was no significant change in dietary intakes except for the fiber supplement. Neither pectin, cellulose, nor lignin significantly altered serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, or the ratio of high-density lipoprotein to total cholesterol in healthy normolipidemic subjects over four weeks.

Temporary inhibition of platelet function with iloprost (ZK36374) preserves canine platelets during extracorporeal membrane oxygenation.

Contact between blood and artificial surfaces results in extensive quantitative and qualitative alterations in platelet function. We evaluated the efficacy of a brief infusion of iloprost (ZK36374), a stable analog of prostacyclin, in preventing these platelet changes during extracorporeal membrane oxygenation. Twelve nonsplenectomized male mongrel dogs (23 to 30 kg) were randomized to treatment (n = 6) and control (n = 6) groups. The treatment animals received an infusion of iloprost at a rate of 150 ng/kg/min with the infusion being terminated 30 minutes after the initiation of extracorporeal membrane oxygenation, despite the fact that all animals were maintained on extracorporeal membrane oxygenation for 3 hours. In the control group, platelet counts dropped to 54% +/- 8.9% (mean +/- standard error of the mean) of initial levels at 30 minutes of extracorporeal membrane oxygenation and gradually rose to 87.2% +/- 6.7% at 3 hours. In contrast, the platelet counts of the iloprost-treated dogs remained stable throughout extracorporeal membrane oxygenation at 98.3% +/- 4.2% of initial counts. Platelet reactivity toward adenosine diphosphate revealed a significant and permanent loss of platelet function in the control group (37.0% +/- 2.1% inhibition). In contrast, the iloprost group demonstrated significant inhibition of platelet reactivity (79.2% +/- 8.3%) during the iloprost infusion but a return to normal function (4.2% +/- 6.7% inhibition) after cessation of drug infusion which persisted throughout extracorporeal membrane oxygenation. Plasma levels of the platelet-specific protein thrombospondin rose progressively from 918 +/- 89 ng/ml to 1465 +/- 239 ng/ml (delta 548 +/- 179 ng/ml) at 30 minutes of extracorporeal membrane oxygenation, which indicates extensive release of platelet granule contents (p less than 0.05). In contrast, plasma thrombospondin levels in the iloprost group demonstrated no additional rise after cessation of the iloprost infusion. In conclusion, iloprost effectively preserves platelet number and function during extracorporeal circulation. The fact that its salutary effects outlast its presence in plasma suggests that prevention of initial platelet-synthetic surface interactions permits the appearance of reduced surface affinity for platelets and, thus, reduced synthetic surface thrombogenicity.

Efficacy of iloprost (ZK36374) versus aspirin in preventing heparin-induced platelet activation during cardiac operations.

For patients with heparin-induced platelet activation, reexposure to heparin can result in profound thrombocytopenia, intravascular thrombosis, and hemorrhage. We compared the ability of aspirin to that of iloprost (ZK36374), an analogue of prostacyclin, in preventing heparin-induced platelet activation and thus permitting a cardiac operation in a patient with heparin-induced platelet activation. Despite abolishing thromboxane A2 synthesis, aspirin (4 mmol/L) failed to prevent either in vitro heparin-induced platelet aggregation (65.0% without versus 59% with aspirin) or carbon 14-serotonin release (81.8% without versus 59.7% with aspirin). In contrast, iloprost (0.01 mumol/L) prevented both in vitro heparin-induced platelet aggregation (65% without versus 5.0% with iloprost) and release (81.8% without versus 0% with iloprost). Consequently, a continuous infusion of iloprost was begun before administration of heparin, continued throughout cardiopulmonary bypass, and discontinued 15 minutes after administration of protamine. The whole blood platelet count (209,000/microliter) remained stable after intraoperative administration of heparin (238,000/microliter) and was 115,000/microliter after the operation. No spontaneous platelet aggregates were observed in samples of platelet-rich plasma after heparin administration, and no platelet transfusions were required. Plasma levels of platelet factor 4 rose from 27 to 725 ng/ml after heparin administration but then declined during bypass to 50 ng/ml. Beta thromboglobulin levels only rose from 92 to 496 ng/ml with administration of heparin. Fibrinopeptide A levels fell from 72 to 22 ng/ml after heparin and remained stable throughout bypass. The template bleeding time was 7.5 minutes preoperatively and 8.0 minutes postoperatively. The postoperative chest tube drainage (12 hours) was 475 ml, and platelets responded normally to adenosine diphosphate. In conclusion, iloprost but not aspirin completely prevented heparin-induced platelet activation in vitro. Furthermore, iloprost effectively prevented this syndrome clinically, which permitted a safe cardiac operation in this patient with heparin-induced platelet activation.

Effects of simulated extracorporeal circulation on human leukocyte elastase release, superoxide generation, and procoagulant activity.

Activated leukocytes are thought to contribute to respiratory dysfunction, alterations in microvascular permeability, disseminated intravascular coagulation, and thrombosis, all of which can complicate extracorporeal circulation. The purpose of this work was to determine the effects of extracorporeal circulation on leukocyte functions likely to mediate organ damage. White blood cell counts in the bubble circuits (n = 5) fell to 51% +/- 7% (mean +/- standard error of the mean; p less than 0.05) of initial levels within 2 hours of recirculation. In contrast, counts from both the spiral coil (n = 5) and hollow-fiber (n = 5) groups remained at 91% +/- 12% and 100%, respectively. Plasma levels of human neutrophil elastase rose from 0.28 +/- 0.06 micrograms/ml to 3.14 +/- 0.36 micrograms/ml (p less than 0.05) and 0.20 +/- 0.02 micrograms/ml to 1.61 +/- 0.35 micrograms/ml (p less than 0.05) in bubble and spiral coil circuits, respectively, but from only 0.20 +/- 0.03 micrograms/ml to 0.96 +/- 0.42 micrograms/ml in the hollow-fiber circuit despite 2 hours of recirculation. Consistently, in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine, a chemotactic peptide, cells from spiral coil and bubble circuits released and generated significantly less elastase and superoxide anion, respectively. In contrast, neutrophils from the hollow-fiber circuits demonstrated enhancement of N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced elastase release and superoxide generation. Finally, mixed leukocytes from all circuits expressed procoagulant activity reaching statistical significance in bubble circuits. In conclusion, extracorporeal circulation has pronounced effects on neutrophil elastase release, superoxide anion generation, and leukocyte procoagulant activity. Spiral coil and bubble oxygenators cause granule release and, subsequently, reduced sensitivity to soluble agonists. In contrast, hollow-fiber oxygenators "prime" cells, actually enhancing reactivity. Recirculation through all circuits induces leukocyte procoagulant activity that is likely to contribute to surface-induced thromboses and excessive bleeding.

The effects of Carmeda Bioactive Surface on human blood components during simulated extracorporeal circulation.

Postoperative morbidity after cardiopulmonary bypass most commonly manifests as bleeding diatheses or pulmonary dysfunction. The pathophysiology has been attributed to the activation of cellular and humoral components of blood after contact with an artificial surface. Development of a surface that would be nonthrombogenic and also would constitute a less potent inflammatory stimulus would therefore be beneficial. In the following experiments, we evaluated the heparin-bonded Carmeda Bioactive Surface (Medtronics Cardiopulmonary, Anaheim, Calif.) in an in vitro model of extracorporeal circulation at standard-dose heparin (5 U/ml), to examine the effects of the surface treatment on activation of blood elements, and at reduced-dose heparin (1 U/ml), to determine whether surface-bound heparin would serve as an effective anticoagulant. During the initial recirculation period, platelet counts in the Carmeda (n = 12) circuits were preserved at both doses of heparin and compared with control values (n = 12): At 5 U/ml, control 36% +/- 4% (mean +/- standard error of the mean) versus Carmeda 81% +/- 5%; at 1 U/ml, 43% +/- 3% versus 61% +/- 10%, expressed as a percent of baseline at 30 minutes, p < 0.05. Furthermore, plasma levels of platelet factor 4 and beta-thromboglobulin were significantly reduced in the Carmeda circuits throughout the experiment: At heparin 5 U/ml, 2500 +/- 340 ng/ml versus 604 +/- 191 ng/ml; at 1 U/ml, 2933 +/- 275 ng/ml versus 577 +/- 164 ng/ml of platelet factor 4 at 2 hours (p < 0.05). The pattern of beta-thromboglobulin release was similar, with effects more pronounced at the lower dose of heparin. Surface modification also reduced leukocyte depletion (p < 0.05) and release of elastase at both concentrations of heparin (5 U/ml, 0.72 +/- 0.29 ng/ml versus 0.33 +/- 0.23 ng/ml; 1 U/ml, 0.85 +/- 0.08 ng/ml versus 0.20 +/- 0.05 ng/ml, at 2 hours, p < 0.05). Moreover, as heparin concentration was reduced, Carmeda surface treatment significantly decreased generation of C3a des Arg (1 U/ml, 14,410 +/- 3558 ng/ml versus 3053 +/- 1039 ng/ml at 2 hours, p < 0.05). Although heparin bonding was originally intended to obviate the need for systemic heparinization, Carmeda treatment did not reduce fibrinopeptide A generation at the lower dose of heparin. In summary, Carmeda treatment failed to exhibit anticoagulant efficacy in this model; however, the data suggest that surface modification may have a role in ameliorating the typical inflammatory response initiated by blood contact with an artificial surface.

Iloprost (ZK36374), a stable analogue of prostacyclin, preserves platelets during simulated extracorporeal circulation.

Contact between blood and synthetic surfaces of an extracorporeal circuit results in extensive alterations in platelet function. These platelet abnormalities have been reproduced in vitro by recirculating heparinized (5 units/ml) human blood at 37 degrees C in a silicone rubber circuit (0.1 m2) containing a spiral coil membrane oxygenator (0.9 m2). During control recirculation trials, platelet counts fell to 29% +/- 8% (mean +/- standard error of the mean) of initial levels within 30 minutes, and sensitivity to the soluble agonists, adenosine diphosphate and epinephrine, disappeared. Plasma levels of the platelet-specific protein platelet factor 4 rose to 2,600 +/- 200 ng/ml, indicating extensive platelet granule release. Similarly, plasma concentrations of thromboxane B2 rose from less than or equal to 100 pg/ml to 500 +/- 200 pg/ml at 120 minutes, and transmission electron microscopy demonstrated disruption of platelet subcellular architecture. In contrast, when ilioprost, a stable prostacyclin derivative (1 ng/ml), was added to the circuit prior to recirculation, the thrombocyte count remained at 85% +/- 4% of initial values. Platelets incubated or recirculated for 2 hours in the presence of iloprost responded normally to both adenosine diphosphate and epinephrine after separation from the drug by gel-filtration. Furthermore, plasma concentrations of platelet factor 4 remained below 300 ng/ml, plasma levels of thromboxane B2 failed to reach detectable levels, and platelet ultrastructure remained intact. Thus, iloprost effectively preserves the circulating platelet count, prevents platelet granule release, and preserves platelet functional and morphological integrity during simulated extracorporeal circulation.

Release of lysosomal hydrolases during simulated extracorporeal circulation.

Contact with surfaces results in activation of formed blood elements. This study demonstrates that during extracorporeal circulation, release of lysosomal enzymes occurs concomitantly with platelet granule secretion. Fresh, heparinized human blood was recirculated for 2 hours at 1,000 ml/min at 37 degrees C in silicone rubber circuits containing a membrane oxygenator (0.85 m2). The plasma levels of a platelet-specific protein, low affinity platelet factor 4 (LA-PF4), rose from less than 0.5 to 16 +/- 3 SEM microgram/ml plasma, indicating extensive release of platelet alpha granule contents. Concurrently, plasma activity of acid phosphatase and N-acetyl-beta-glucosaminidase increased nearly fivefold. Platelet inhibition prevented release of LA-PF4 and reduced acid phosphatase levels, but failed to alter the levels of N-acetyl-beta-glucosaminidase. Lidocaine (10 to 20 microgram/ml), however, prevented the rise in N-acetyl-beta-glucosaminidase activity and diminished acid phosphatase levels without altering secretion of LA-PF4. The failure of platelet inhibitors to block the increase in N-acetyl-beta-glucosaminidase, and the efficacy of lidocaine to do so without altering LA-PF4 secretion, suggest that leukocytes, not platelets, are the primary source of this lysosomal enzyme. Although acid phosphatase activity measured in plasma my be derived from leukocytes, platelet membranes, and not lysosomes, appear to be a more likely source. Release of hydrolytic enzymes from formed blood elements during cardiopulmonary bypass may cause endothelial cell injury and thus contribute to the increased vascular permeability associated with extracorporeal circulation.

Prevention of heparin-induced thrombocytopenia during open heart surgery with iloprost (ZK36374).

Recurrent thrombocytopenia, thrombosis, or sudden death may develop in patients with heparin-induced thrombocytopenia who are reexposed to heparin. Three patients came to us in whom a diagnosis of heparin-induced thrombocytopenia had been made on the basis of clinical and serologic evidence; these patients required reexposure to heparin because of urgent cardiac surgery. Therefore, we evaluated the ability of iloprost (ZK36374), a new analogue of prostacyclin, to prevent heparin-dependent activation of platelets and thereby permit obligatory heparinization for safe extracorporeal circulation. Before operation, we demonstrated that iloprost prevented both heparin-dependent platelet aggregation and tritiated (3H)-serotonin release in vitro. Therefore a continuous infusion of iloprost was begun 1 hour before heparinization and was continued throughout cardiopulmonary bypass and for an additional 15 minutes after protamine administration. The mean platelet count of 130,000/microliters before operation remained stable, and no spontaneous platelet aggregation was observed in samples of platelet-rich plasma obtained before cardiopulmonary bypass but after heparin administration. Similarly, after heparin administration but before bypass, platelet responsiveness to adenosine diphosphate remained unchanged when compared with preoperative values. Plasma levels of platelet factor 4 increased from 26 +/- 1 ng/ml (mean +/- standard error) to 843 +/- 383 ng/ml after heparin administration but actually decreased throughout cardiopulmonary bypass to 52 +/- 25 ng/ml. Beta-thromboglobulin levels increased from 103 +/- 16 to 244 +/- 94 ng/ml with heparinization. The mean bleeding time was 10.5 minutes preoperatively and 13.3 minutes postoperatively. The mean amount of postoperative chest tube drainage (duration: 12 hours) was 432 +/- 67 ml. Thus, despite the confirmed presence of heparin-dependent platelet-activating factor in the plasma of these three patients, iloprost prevented heparin-induced platelet activation during cardiopulmonary bypass while preserving platelet function, as would be desired for postoperative hemostasis.

Mediation of cardiac ischemia by thromboxanes released from human platelets.

We evaluated the consequences of platelet activation within the coronary circulation and determined the contribution of released thromboxanes, the most potent vasoconstrictors known, to the ensuing cardiac ischemia. Human platelets were isolated by sepharose column chromatography from blood of normal donors and added to the crystalloid perfusate of a Langendorff rabbit heart (platelet counts greater than or equal to 10,000/microliters). Following thrombin-induced (1 U/ml) platelet activation, the coronary flow decreased by 30 +/- 10% (mean +/- SEM, P less than 0.02), the mean concentration of thromboxane B2 in the coronary sinus effluent rose to 62 +/- 25 pmol/ml, and immediate, often irreversible cardiac ischemia as monitored by nicotinamide adenine dehydrogenase autofluorescence photography, ensued. However, with high concentrations of the platelet inhibitor and vasodilator, prostaglandin E1 (1.0 mM), the coronary flow increased by 50 +/-= 15%, and the epicardial fluorescence remained unchanged despite a small (10 +/- 3 pmol/ml) increase in coronary sinus thromboxanes. Platelets isolated from donors who ingested aspirin were incapable of thromboxane synthesis (less than 5 pmol/ml) but remained normally responsive to thrombin-induced activation. When these platelets were challenged by thrombin during cardiac perfusion, however, coronary flow and epicardial fluorescence remained unchanged. We conclude that platelet activation within the coronary circulation can induce irreversible cardiac ischemia, which, however, can be prevented by appropriate pharmacologic inhibition of platelet function. Furthermore, the fact that cardiac perfusion was preserved during a thrombin challenge of platelets from aspirin-treated donors establishes a fundamental role for the products of cyclooxygenase activity (e.g., thromboxanes) in the genesis of this form of myocardial ischemia.

Preliminary characterization of the procoagulant material in human ascites.

Disseminated intravascular coagulation invariably accompanies placement of peritoneovenous (LeVeen) shunts, which suggests that ascitic fluid contains procoagulant material capable of activating blood coagulation. In this study, we identified thrombogenic activity in human ascites and the hemostatic pathway by which it acts. Peritoneal fluid was removed percutaneously from patients with ascites due to various causes. Four fractions were prepared by centrifugation: cells, a low-speed, cell-free fluid, a high-speed supernatant, and the precipitate from the high-speed centrifugation. Cellular fractions from all ascitic fluids shortened a one-stage clotting time of normal pooled plasma by 68% in comparison with saline solution and endotoxin controls. Similarly, the cell-free fluids also shortened the clotting time of normal pooled plasma by 41%. The cellular and cell-free fractions shortened the clotting time of factor VIII-deficient plasma but failed to demonstrate procoagulant activity in factor VII-deficient plasma. These fractions had no effect on platelet aggregation or the platelet release reaction. The high-speed precipitate was dissociated by ethylenediaminetetra-acetate (EDTA) into fluid phase and precipitate, both of which demonstrated procoagulant activity. Furthermore, high-speed precipitate contained protein, phospholipid, and sterol in proportions similar to those of plasma membranes and contained membrane-bound vesicles as identified by means of electron microscopy. This material could be rendered inactive by heating to 100 degrees C for 2 minutes or by incubation with phospholipase C for 15 minutes. Finally, the ability of the high-speed precipitate to shorten the clotting time was prevented by preincubation with a monoclonal antibody, which is known to inhibit the procoagulant activity of human tissue factor. We suggest that several entities contribute to the procoagulant properties of human ascites, with procoagulant material deriving at least in part from peritoneal cells. The sedimentable procoagulant factor appears to be associated with cellular membranes or membrane fragments and is thromboplastin-like in its chemical composition, immunoreactivity, and substrate specificity.

Early fungal endocarditis in homograft recipients.

Retrospective analysis of 200 homograft valve recipients at our institution revealed two cases of fungal endocarditis. Pathogenesis appears to be related to either recipient seeding in one elderly immunocompromised patient or a previously contaminated donor valve implanted in an otherwise healthy recipient. Therefore, our experience underscores the need for both meticulous prevention of fungal infection preoperatively in the recipient and elimination of previously contaminated homograft valves from the donor pool.