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Biomedical subjects

A Bass

Publications and source records attributed to A Bass.

At least 55 records · Page 3Linked to original sources

Antihemostatic and antithrombotic effects of monoclonal antibodies against von Willebrand factor in nonhuman primates.

BACKGROUND: Because the adhesive glycoprotein von Willebrand Factor (vWF) mediates initial platelet attachment at sites of vascular injury and may also contribute to shear-dependent platelet thrombus formation, we have determined in vivo the relative antithrombotic efficacy and hemostatic safety of infusing murine monoclonal antibodies against vWF. METHODS: In baboons with chronic arteriovenous shunts, thrombus formation was initiated by interposition of thrombogenic Dacron vascular grafts (VG) and endarterectomized baboon aortic segments (EAS). Thrombus formation on VG and EAS was assessed by use of real-time scintillation camera imaging of indium 111-labeled platelet deposition. In control and treated animals (anti-vWF antibody) platelet hemostatic competence was evaluated by means of serial measurements of platelet count, bleeding time, and ex vivo platelet aggregation in response to adenosine diphosphate and ristocetin. RESULTS: Although bolus antibody infusions did not affect circulating platelet counts, bleeding times were immediately prolonged to 28 +/- 4 minutes (vs 4.7 +/- 0.4 minutes before treatment, p = 0.01). Bleeding times normalized within 24 hours after antibody administration. Platelet aggregation in response to adenosine diphosphate was unchanged by antibody therapy, whereas ristocetin-induced platelet aggregation was abolished acutely and remained impaired for 24 hours. Platelet deposition on VG after 60 minutes of exposure to flowing blood was 2.95 +/- 0.74 x 10(9) platelets/cm in six control animals as compared to 1.86 +/- 0.16 x 10(9) platelets/cm in five treated animals (p = 0.04). Similarly, platelet deposition on EAS averaged 4.40 +/- 0.89 x 10(9) platelets/cm in control studies and was reduced significantly by antibody therapy (1.52 +/- 0.50 x 10(9) platelets/cm, p = 0.02). CONCLUSIONS: Despite profound interruption of platelet hemostatic functions, therapeutic targeting of vWF modestly inhibits platelet-dependent thrombosis.

Animals↗

Combined carotid endarterectomy and coronary artery revascularization: a sobering review.

The clinical outcome of 99 patients who underwent combined single-stage carotid thromboendarterectomy and coronary artery bypass grafts in three different hospitals over a 15-year period was analyzed. Coronary revascularization was elective in 16 patients, urgent in 46 and emergent in 37 patients. Asymptomatic carotid artery stenosis of greater than or equal to 80% was detected in 79% of patients. Sequential reconstruction of the carotid artery circulation followed by restoration of the coronary circulation was performed in all patients by two separate surgical teams. The population included 79 men and 20 women, with a mean age of 67 +/- 6 years, of whom 53% had a previous myocardial infarction, 59% had hypertension and 49% had a history of smoking. Three or more coronary arteries were revascularized in 90% of patients. The overall major neurological complication rate was 25%, with an 11% stroke rate ipsilateral to the operated carotid. Other major complications included respiratory failure (5%), multisystem failure (8%), and myocardial infarction (8%). The overall mortality was 12%. Ten of the 12 deaths were directly related to the cardiac operation, and 2 died as a result of stroke. We conclude that a combined carotid and coronary artery operation results in a high morbidity and mortality in institutions with excellent records for each operation when performed separately. Whenever possible, these high risk patients should be carefully assessed regarding the need for both procedures, since prophylactic carotid endarterectomy has not been shown to significantly reduce the neurologic risk of coronary bypass.

Aged↗

Hirudin interruption of heparin-resistant arterial thrombus formation in baboons.

To determine the role of thrombin in high blood flow, platelet-dependent thrombotic and hemostatic processes we measured the relative antithrombotic and antihemostatic effects in baboons of hirudin, a highly potent and specific antithrombin, and compared the effects of heparin, an antithrombin III-dependent inhibitor of thrombin. Thrombus formation was determined in vivo using three relevant models (homologous endarterectomized aorta, collagen-coated tubing, and Dacron vascular graft) by measuring: (1) platelet deposition, using gamma camera imaging of 111In-platelets; (2) fibrin deposition, as assessed by the incorporation of circulating 125I-fibrinogen; and (3) occlusion. The continuous intravenous infusion of 1, 5, and 20 nmol/kg per minute of recombinant hirudin (desulfatohirudin) maintained constant plasma levels of 0.16 +/- 0.03, 0.79 +/- 0.44, and 3.3 +/- 0.77 mumol/mL, respectively. Hirudin interrupted platelet and fibrin deposition in a dose-dependent manner that was profound at the highest dose for all three thrombogenic surfaces and significant at the lowest dose for thrombus formation on endarterectomized aorta. Thrombotic occlusion was prevented by all doses studied. In contrast, heparin did not inhibit either platelet or fibrin deposition when administered at a dose that maximally prolonged clotting times (100 U/kg) (P greater than .1), and only intermediate effects were produced at 10-fold that dose (1,000 U/kg). Moreover, heparin did not prevent occlusion of the test segments. Hirudin inhibited platelet hemostatic function in concert with its antithrombotic effects (bleeding times were prolonged by the intermediate and higher doses). By comparison, intravenous heparin failed to affect the bleeding time at the 100 U/kg dose (P greater than .5), and only minimally prolonged the bleeding time at the 1,000 U/kg dose (P less than .05). We conclude that platelet-dependent thrombotic and hemostatic processes are thrombin-mediated and that the biologic antithrombin hirudin produces a potent, dose-dependent inhibition of arterial thrombus formation that greatly exceeds the minimal antithrombotic effects produced by heparin.

Animals↗

[Surgery for thoraco-abdominal aortic aneurysm].

12 patients underwent resection of a thoraco-abdominal aortic aneurysm. There were 10 men and 2 women, ranging in age from 54-78 years (mean 65). Aortic arteriosclerosis was the primary etiology in 11, and Behcet's disease in the other 1. Most patients (7/12) presented with Type 3 aneurysm, extending from the distal descending thoracic aorta to the distal abdominal aorta; none had aortic dissection. 11 were operated on for symptoms related to the aneurysm: 3 of these had a contained rupture. The risk factors were chronic obstructive pulmonary disease in 10, hypertension (10), diffuse arteriosclerosis (8), ischemic heart disease (6), chronic renal failure (5) and cerebrovascular accident (1). The surgical technique in 11 was graft inclusion and visceral vessel reattachment. The main complication was acute renal failure, seen in 3 patients. None had spinal ischemia. Operative mortality was 33%. Of the 4 who died, 2 had myocardial infarction and 2 uncontrolled intraoperative bleeding. According to the literature the major complications are spinal cord ischemia and renal failure.

Acute Kidney Injury↗

Pulse volume recording disturbances in paraplegic patients.

Spinal cord injuries may modify vascular reactivity in the denervated region. This study presents an original observation of altered vascular response in paraplegic patients. A group of 30 consecutive paraplegic otherwise normal individuals underwent a thorough vascular examination. There were 29 male and 1 female patient, 21 to 67 years old (average 41), all with traumatic spinal cord injury. Average time since injury was 17 years. All had good peripheral pulses and normal segmental Doppler pressure measurements. In 8 patients, plethysmography--pulse volume recording (PVR) was normal as expected. In 22 patients an unusual feature of the vascular examination was recorded, consisting of normal peripheral arterial pressures with PVR waveforms indicating poor pulsatility. This group was older than the group with normal studies: ages 44 +/- 13 vs 34 +/- 8 years (p = 0.05), and more time had elapsed since injury-20 +/- 12 vs 10 +/- 4 years (p = 0.015). The altered pulsatility demonstrated in most of those paraplegic patients may play a role in deficient wound healing frequently observed below the level of spinal neurological loss.

Adult↗

Inter- and intrasexual dimorphisms in the vocal control system of a teleost fish: motor axon number and size.

In one species of vocalizing fish, the plainfin midshipman (Porichthys notatus), large, nest-guarding males ('type I') use striated muscles to produce acoustic communication signals that include short duration (less than 1 s) 'burps' important in agonistic encounters and long duration (in the order of minutes) 'hums' which function in attracting females to nest sites during the breeding season. Females, and a second group of smaller reproductively active males ('type II') that 'sneak' spawn, do not generate hums, although they produce burps. Differences in vocal behavior are paralled by a relative increase of 6-fold in the sonic muscle of type I males. Inter- and intrasexual dimorphisms in sonic muscle mass were matched by those in the cross-sectional area of sonic motor axons, but not by those in number of axons. Thus, axon size was 2- to 3-fold larger in type I males than in females, type II males, or juveniles, none of which differed significantly from each other. Axon number was similar between type I males and females of a similar body size, despite the extreme dimorphism in sonic muscle mass. Axon number, however, was slightly greater (0.1-fold) in type I males and females compared to the smaller-sized juveniles and type II males. Type II males, in comparison to the non-reproductive juvenile males, have gonads that are about 20-fold larger and produce mature sperm. Nevertheless, the two groups resemble each other in body and swimbladder size, as well as sonic motor axon size and number. This suggests that type II males represent a subset of juvenile males that undergo precocious gonadal hypertrophy and spermiogenesis, but retain juvenile-like nongonadal traits. The results are discussed within the context of the development of vertebrate motor systems as well as the evolution of alternative reproductive tactics among teleost fishes.

Air Sacs↗

Evolution of homologous vocal control traits.

Evolutionary neurobiologists want to know how neuronal properties (or traits) have been modified to subserve adaptive changes in behavioral phenotypes. Homology can provide a conceptual framework to distinguish the separate contributions of phylogenetic factors and current adaptive modifications to extant traits and behaviors. In this essay, a suite of nine vocal/sonic motor traits are compared in two orders of teleost fishes, the Batrachoidiformes and Scorpaeniformes. Only three of the traits are modified among Scorpaeniformes, the more advanced group. The large number of conserved characters among the study species suggests their sonic motor systems are homologs. This conclusion is consistent with the known phylogeny of teleosts and further implies that homologous sonic motor traits are more extensively modified among more recently evolved members (in this case the Scorpaeniformes) of the teleostean lineage. Since homology implies a common ontogenetic history for any trait, modifications thereof can potentially be linked to changes in identifiable developmental events, which themselves are homologs. Several hypotheses are proposed to account for the origins of modified sonic traits. The further demonstration that modified traits of the sonic motor system are in fact adaptations sets the stage for behavioral ecological studies that attempt to understand why the modified traits underlie behavioral changes that increase an individual's fitness.

Animal Communication↗

Reduction in thrombus formation by placement of endovascular stents at endarterectomy sites in baboon carotid arteries.

BACKGROUND: Although antithrombotic therapies with aspirin, dipyridamole, and heparin have decreased thrombo-occlusive events, they have not abolished these complications. Endovascular mechanical support, first reported by Dotter in 1969, has been proposed as a means to reduce both acute and chronic vessel closure by providing a supporting framework for the disrupted and sometimes dissected arterial wall. METHODS AND RESULTS: To determine the effects of placing self-expanding stainless steel wire endoprostheses on the accumulation of thrombus at sites of carotid artery endarterectomy we measured platelet deposition continuously for 90 minutes and at 24 and 48 hours by gamma camera imaging of autologous 111In-labeled platelets in six stented and nonstented endarterectomized baboons that received heparin but no antiplatelet agents. At nonstented endarterectomy sites 5.36 +/- 1.25 x 10(8), 4.78 +/- 0.98 x 10(8), and 4.55 +/- 0.81 x 10(8) platelets per cm were deposited at 30, 60, and 90 minutes, respectively. In contrast, stented endarterectomy sites accumulated 0.99 +/- 0.31 x 10(8), 0.66 +/- 0.33 x 10(8), and 0.80 +/- 0.36 x 10(8) platelets per cm at 30 minutes (p = 0.02), 60 minutes (p = 0.004), and 90 minutes (p = 0.002), respectively. Platelet deposition remained reduced at 24 and 48 hours in stented endarterectomized carotid arteries (ECAs) when assessed as a ratio between net radioactivity in the endarterectomized region versus whole blood radioactivity (p = 0.006 and p = 0.009, respectively). Both stented and nonstented ECAs remained patent acutely, although two of six nonstented ECAs occluded by 30 days. By comparison 11 of 14 nonstented ECAs remained patent in another group of control animals. Scanning electron microscopy of control and stented arteries at 30 days demonstrated equivalently confluent endothelium. CONCLUSIONS: We postulate that endovascular stents reduce the thrombogenic effects of flap formation, tearing, dissection, and vasospasm in ECAs.

Animals↗

Sexual dimorphisms in the vocal control system of a teleost fish: ultrastructure of neuromuscular junctions.

In the sound-generating fish, Porichthys notatus, large, nest-guarding 'Type I' males use their swimbladder 'drumming' muscles to produce acoustic communication signals. Females and another group of smaller sexually mature males ('Type II') have not been observed to produce sounds. Electron microscopy was used to compare the morphology of the neuromuscular junctions in vocalizing Type I males to those of Type II males and females. Significant differences were seen in synaptic vesicle density, terminal size, degree of terminal invagination below the muscle fiber surface, number of Schwann cell processes along the non-synaptic boundary of boutons, and the number of boutons per innervation site.

Air Sacs↗

Utility of computed tomography for surveillance of small abdominal aortic aneurysms. Preliminary report.

To assess the ability of computed tomography to predict the potential for expansion of small abdominal aortic aneurysms, we analyzed the computed tomographic scans of 30 patients who had two or more abdominal computed tomographic scans at least 6 months apart between 1979 and 1989. Clinical variables and 10 defined objective characteristics of computed tomography were evaluated. Twenty-five men and five women with abdominal aortic aneurysms ranging from 30 to 64 mm (mean, 45 mm) were followed up with serial computed tomographic scans for a mean (+/- SE) of 26 +/- 3 months. In 19 patients, enlargement of aneurysm diameter of 3 mm or more on serial computed tomographic scans was noted, whereas in 11, there was little or no expansion. Of the clinical variables studied, only serum cholesterol correlated with an increased risk of expansion. Thrombus area, measured by computed tomography, was 7.3 +/- 0.9 cm2 in enlarging aneurysms vs 4.3 +/- 0.9 cm2 in stable aneurysms. Based on these preliminary data, we conclude that computed tomography may provide valuable information about the likelihood of future expansion of small abdominal aortic aneurysms.

Adult↗

Heparin-resistant thrombus formation by endovascular stents in baboons. Interruption by a synthetic antithrombin.

Intravascular mechanical support has been proposed as a solution to the frequent occurrence of vascular narrowing and occlusion after transluminal balloon angioplasty or surgical endarterectomy. Although several endovascular stents are currently in clinical use for angioplasty of larger vessels, acute thrombosis is a troublesome complication of their use with coronary angioplasty. To study thrombus formation associated with metallic mesh endoprostheses, we have evaluated stents placed inside 3-mm expanded polytetrafluoroethylene (ePTFE) grafts incorporated into chronic exteriorized arteriovenous silicone rubber shunts in baboons. We have also compared the antithrombotic capacities of heparin and the synthetic antithrombin D-phenylalanyl-L-prolyl-L-arginyl-chloromethylkene (D-FPRCH2Cl) to interrupt this platelet-dependent process for two different endovascular stents. Acute platelet deposition was continuously measured during 1 hour using gamma camera imaging of platelets labeled with indium-111 oxine. On untreated control ePTFE grafts (n = 11), 0.87 +/- 0.15 x 10(9) platelets/cm were deposited during 60 minutes. In contrast, balloon-expandable endovascular stents within ePTFE (n = 6) accumulated 4.37 +/- 0.68 x 10(9) platelets/cm (p = 0.003 compared with controls), and self-expandable stents (n = 6) accumulated 3.91 +/- 0.42 x 10(9) platelets/cm (p = 0.006 compared with controls); no difference between stents was detected in this test system (p greater than 0.5). Systemic heparin treatment did not reduce platelet deposition (4.20 +/- 0.41 x 10(9) platelets/cm at 60 minutes; p greater than 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Chloromethyl Ketones↗

Comparison of transcranial and cervical continuous-wave Doppler in the evaluation of intracranial collateral circulation.

Adequate intracranial collateral circulation reduces risk of stroke in carotid artery surgery. To evaluate their relative accuracies in assessing intracranial collateral blood flow, we prospectively compared transcranial Doppler and continuous-wave Doppler of the cervical carotid arteries combined with compression of the common carotid artery in 28 consecutive patients before carotid endarterectomy. Ten healthy volunteers served as controls. Three patients (11%) were excluded from compression of arteries because of diffuse disease in the common carotid artery. A total of 199 compressions were performed without complications. Lack of a suitable transtemporal window precluded the performance of transcranial Doppler in three patients (12%). The anterior communicating artery was identified in all the normal volunteers and 80% of patients by both methods. The posterior communicating artery was identified by both methods in 16 of 20 attempts in controls. Continuous-wave Doppler identified the posterior communicating artery in 30 of 50 attempts in patients; transcranial Doppler identified the posterior communicating artery in 20 of 44 attempts in patients (p greater than 0.5). Detection of intracranial collaterals correlated with intraoperative carotid artery back pressure measurements in 23 of 25 patients (92%). We conclude that continuous-wave Doppler of the extracranial arteries combined with common carotid artery compression is a safe and easy way to detect intracranial collaterals, with an accuracy equivalent to transcranial Doppler.

Adult↗

Duplex ultrasound analysis of operated carotid arteries in baboons.

Duplex ultrasound analysis, which combines high-resolution B-mode imaging and Doppler spectral flow analysis, was used to examine 3 to 4 mm in diameter normal [n = 24] and mechanically manipulated baboon carotid arteries (endarterectomies [n = 10], construction of interposition vascular grafts [n = 10], and placement of endovascular stents within interposition grafts [n = 4]). Patency or occlusion was definitively confirmed by direct visualization and palpation during surgical exploration at defined intervals or by postmortem histologic examination. Duplex examination accurately demonstrated postoperative hemodynamic changes and with only one exception correctly identified patency and occlusion. We conclude that this technique is superior to more invasive methods for verification of the outcome of operations on small arteries in experimental animals.

Animals↗

Propagation of deep venous thrombosis identified by duplex ultrasonography.

To investigate the efficacy of anticoagulation in preventing continuing thrombosis, we prospectively evaluated 24 patients with acute deep venous thrombosis using duplex ultrasonography. All patients were hospitalized with conclusive ultrasonic evidence of deep venous thrombosis identified in one of four levels: I, calf only; II, calf-popliteal; III, calf-popliteal-femoral; or IV, calf-popliteal-femoral-iliac. Duplex scans were obtained on admission and on three subsequent occasions during therapy. Progression of thrombosis was defined as advancement of thrombus to the more proximal venous level. Demographic data, symptoms, risk factors for deep venous thrombosis, physical findings, anticoagulation regimens, and hematologic variables were ascertained. Adequacy of anticoagulation was defined as elevation of baseline activated partial thromboplastin time by 150%. Nine patients (38%) had progression of thrombosis, and 15 (62%) had stable or improving duplex scans. Progression occurred as follows: I----II (2), I----III (2), II----III (1), and III----IV (4). Of the demographic and clinical variables examined, only smoking correlated with progression of thrombus (p = 0.04). Average heparin dose in the stable group was 1214 +/- 294 units/hr and 1122 +/- 248 units/hr in the group that progressed (p = 0.8): activated partial thromboplastin time was 45.6 +/- 7 seconds in the stable group and 49.8 +/- 9 seconds in the progression group (p = 0.7). Nine patients in the stable group had consistently adequate anticoagulation, whereas six did not; six in the progression group were consistently anticoagulated, and three were not. Two patients (one with stable thrombus and one with progressive thrombus) suffered nonfatal pulmonary emboli. Clot progression as determined by duplex scanning did not predict acute complications of deep venous thrombosis.

Adult↗

Different activities of energy metabolism enzymes in children's cardiac atria and ventricles.

Tissue samples from the right atrium and ventricle of the same heart were obtained during surgery on 45 children operated on for congenital heart disease (tetralogy of Fallot, ventricular septal defect). Significant enzyme activity differences were found between atrial and ventricular muscle. Aerobic metabolism enzymes (citrate synthase, malate dehydrogenase), with lactate metabolism (lactate dehydrogenase) and fatty acid oxidation (hydroxyacyl-SoA dehydrogenase) showed significantly higher activities in ventricular muscle tissue. In contrast, hexokinase, the enzyme responsible for glucose phosphorylation was significantly higher in the atria. Hence, the right ventricle can utilize and oxidize to the full all the main nutrients (fatty acids, glucose and lactate) while the right atrium utilizes primarily glucose. These atrio-ventricular differences are independent of the type of congenital heart disease and their existence can be presumed in healthy persons, too.

3-Hydroxyacyl CoA Dehydrogenases↗

Aspirin-independent antithrombotic effects of acutely attached cultured endothelial cells on endarterectomized arteries.

We have compared the acute antithrombotic effects of aspirin-treated versus normal endothelial cell (EC) coverage of endarterectomized baboon aortic segments (EAS) incorporated into chronic exteriorized arteriovenous shunts in baboons. Human ECs grown in culture were incubated in control medium or medium containing aspirin (100 mumols/ml) and then attached at saturation density by incubating EC suspensions (6 x 10(5) cells/100 microliters) within EAS for 20 minutes. Nonendarterectomized aortic segments and untreated EAS served as negative and positive controls, respectively. The inhibitory effect of aspirin treatment on EC production of prostacyclin was confirmed by radioimmunoassay of its stable metabolic breakdown product, 6-keto-prostaglandin F1 alpha in supernatant medium. Thrombus formation in vivo was measured as the accumulation of indium 111-labeled platelets on endarterectomy sites in real time by scintillation camera imaging. 111In-labeled platelets were deposited rapidly, reaching a plateau by 60 minutes of 4.40 +/- 0.89 x 10(9) platelets/cm, compared with 111In-labled platelet deposition on nonendarterectomized segments of 0.89 +/- 0.26 x 10(9) platelets/cm (p = 0.008). Coverage of EAS with normal cultured ECs significantly reduced platelet deposition on EAS (1.05 +/- 0.45 x 10(9) platelets/cm; p = 0.009 at 1 hour compared with EAS not incubated with ECs). Aspirin-treated ECs also produced a marked reduction in platelet disposition (0.71 +/- 0.24 x 10 platelets/cm; p = 0.007 compared with EAS without ECs) that was equivalent to the effect of non-aspirin-treated ECs (p greater than 0.5). Scanning and transmission electron microscopy confirmed the antithrombotic effects of attached ECs. We conclude that endarterectomy of normal arteries produces a highly thrombogenic surface and the thrombogenicity is abolished by acutely attaching cultured human ECs.

Animals↗

[Adaptation of cardiac energy metabolism in children with congenital heart defects].

Metabolic differences of the cardiac muscle in children with normoxaemic and hypoxaemic congenital heart disease were analyzed by means of representative enzymes of the energy metabolism in 95 specimens in 80 children with congenital heart disease. Tissue specimens from the right atria and ventricles were obtained during surgical operations. It was revealed that the myocardial metabolism of patients with congenital heart disease was markedly influenced by hypoxaemia: the aerobic capacity was significantly reduced in the atria as well as in the ventricles. Changes in the atrial musculature were, however, more marked: in addition to citrate synthase - similarly as in the ventricles - in the atria also activities of enzymes associated with lactate metabolism (LDH) and with glycolysis (TPDH, GPDH) were reduced. Patients with an atrial septal defect had a significantly lower activity of the enzyme involved in the fatty acid breakdown (HOADH) than patients with a ventricular septal defect. The described new adaptive mechanism is of practical importance for the treatment of congenital heart disease and other conditions associated with prolonged hypoxaemia.

Adaptation, Physiological↗