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The endovascular delivery of platinum alloy bare metal coils has been widely adapted to treat intracranial aneurysms. Despite the widespread clinical use of this technique, numerous suboptimal outcomes are possible. These may include... more
The endovascular delivery of platinum alloy bare metal coils has been widely adapted to treat intracranial aneurysms. Despite the widespread clinical use of this technique, numerous suboptimal outcomes are possible. These may include chronic inflammation, low volume filling, coil compaction, and recanalization, all of which can lead to aneurysm recurrence, need for retreatment, and/or potential rupture. This study evaluates a treatment alternative in which polyurethane shape memory polymer (SMP) foam is used as an embolic aneurysm filler. The performance of this treatment method was compared to that of bare metal coils in a head-to-head in vivo study utilizing a porcine vein pouch aneurysm model. After 90 and 180 days post-treatment, gross and histological observations were used to assess aneurysm healing. At 90 days, the foam-treated aneurysms were at an advanced stage of healing compared to the coil-treated aneurysms and showed no signs of chronic inflammation. At 180 days, the fo...
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The purposes of this study were to characterize myocardial cell growth in neonatal rats and investigate the mechanism of binucleation in myocardial cells. To test the hypothesis that binucleated myocardial cells result from karyokinesis... more
The purposes of this study were to characterize myocardial cell growth in neonatal rats and investigate the mechanism of binucleation in myocardial cells. To test the hypothesis that binucleated myocardial cells result from karyokinesis without cytokinesis, experiments were designed to measure the rate of DNA synthesis and the percentage of binucleated myocardial cells in neonatal rats during growth. Estimates of myocardial cell nuclear divisions were obtained from rats pulsed with tritiated thymidine at 17 days of gestation. Autoradiograms were prepared from isolated myocardial cells of rats killed at various ages potpartum, and the number of developed silver halide grains over myocardial cell nuclei was calculated. This estimated the mitotic activity of nuclei. To determine myocardial cell DNA synthesis postpartum, another set of rats were injected at various time periods with 4 hourly doses of tritiated thymidine, and hearts were fixed by perfusion 1 hour later. Labeling index of...
Research Interests: DNA, Growth, Animals, Clinical Sciences, Rats, and 5 moreMyocardium, Tritium, Autoradiography, Thymidine, and Cardiomegaly
A porcine adult ICU model would be useful for several avenues of investigation relevant to the care of critically ill patients. The purpose of the experiments reported here was to test the feasibility of such a model, using healthy swine.... more
A porcine adult ICU model would be useful for several avenues of investigation relevant to the care of critically ill patients. The purpose of the experiments reported here was to test the feasibility of such a model, using healthy swine. Swine (n = 4; body weight, 76 +/- 5 kg) were instrumented with endotracheal, bladder, and central arterial and venous catheters, and were admitted to the intensive care unit (ICU) while undergoing mechanical ventilation under the continuous care of nurses. Cardiopulmonary parameters were monitored continuously, and serum biochemical parameters were measured intermittently. Survival was seven days in subject 1 and five and a half days in subject 2. Subjects 3 and 4 survived an abbreviated protocol (44 and 41 h, respectively). Care of the subjects was complicated by iatrogenic hemorrhage (n = 3), pneumonia (n = 2), and acute respiratory distress syndrome (n = 1). One subject was free of complications. Critically ill swine > or = 70 kg can survive ...
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ABSTRACT Despite the tremendous success of vascular stents in treating occlusive artery disease, failure due to excessive neointimal hyperplasia resulting in the formation of a new blockage (termed restenosis) is still unacceptably high.... more
ABSTRACT Despite the tremendous success of vascular stents in treating occlusive artery disease, failure due to excessive neointimal hyperplasia resulting in the formation of a new blockage (termed restenosis) is still unacceptably high. While drug-eluting stents have reduced restenosis rates in coronary application, many problems (e.g. late term thrombosis, incomplete endothelialization, lack of success in peripheral arteries, hypersensitivity) and high cost still have raised concerns of their exclusive use. Regardless of the failure rates, vascular stenting is the standard treatment for occlusive artery disease, and as their use is likely to continually increase there is an imperative need to increase the success rate of this interventional therapy.
Research Interests: Medicine()
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Renal failure was diagnosed in an 11-mo-old male domestic shorthair cat from a colony with mucopolysaccharidosis type I lysosomal storage disease. Grossly, the kidneys were enlarged and bulged on cut section. Histology revealed tubular... more
Renal failure was diagnosed in an 11-mo-old male domestic shorthair cat from a colony with mucopolysaccharidosis type I lysosomal storage disease. Grossly, the kidneys were enlarged and bulged on cut section. Histology revealed tubular necrosis and regeneration with severe interstitial macrophage accumulation. Tubular epithelial cells and interstitial macrophages were distended by abundant, large cytoplasmic vacuoles. Electron microscopy demonstrated severe tubular epithelial vacuolar degeneration with lysosomes distended by granular debris and mineral precipitates. Interstitial macrophages contained similarly distended lysosomes. Although the initial cause of the tubular injury was not identified, the presence of macrophages laden with storage product most likely exacerbated the disease. The macrophage infiltrate may have caused tubular ischemia by compressing peritubular capillaries and separating tubules from their blood supply. Because the kidney is not normally affected in MPS ...
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The textured, blood-contacting surfaces of the Thermocardiosystems HeartMate left ventricular assist device (LVAD) promote the passivation of the biomaterial caused by the accumulation of an integral coagulum. Commonly, acute,... more
The textured, blood-contacting surfaces of the Thermocardiosystems HeartMate left ventricular assist device (LVAD) promote the passivation of the biomaterial caused by the accumulation of an integral coagulum. Commonly, acute, postimplantation thrombocytopenia causes significant bleeding, requiring surgery or blood transfusions. Chronic complications include thromboembolic microevents that can affect central nervous system function. Pumps, explanted during donor organ transplantation, are often found to have an extensive cellular panus associated with the blood-contacting surfaces of the device. This natural cellular lining suggests a possible strategy for improving the blood biocompatibility of the HeartMate. Therefore, seeding of LVADs with cells genetically engineered to enhance their antithrombotic properties before implantation was investigated as a means to improve biocompatibility for long-term use. Bovine vascular smooth muscle cells genetically engineered to produce nitric ...
Research Interests: Cell Adhesion, Scanning Electron Microscopy, Medicine, Nitric oxide, Animals, and 12 moreClinical Sciences, Cattle, Mechanical Stress, Public health systems and services research, Surface Properties, Thrombosis, Circulation, Continuous Flow Heart Assist Devices, Biocompatible Materials, Equipment Design, Blood platelets, and Cardiovascular medicine and haematology
This study established that human cancer cells (A375 melanoma, HT-29 colon cancer, PC-3p prostate cancer) that were xenografted into suckling opossums could proliferate and globally metastasize as early as 11 days after injection. Light... more
This study established that human cancer cells (A375 melanoma, HT-29 colon cancer, PC-3p prostate cancer) that were xenografted into suckling opossums could proliferate and globally metastasize as early as 11 days after injection. Light and electron microscopic examinations (HT-29 colon cancer) determined that the cellular features exhibited by the xenogeneic human tumors grown in laboratory opossums were consistent with those observed in tumors removed from humans. The tumor induction rate, patterns of tumor growth and regression, and types of host immune responses against the xenografted tumors were influenced by injection dosages, injection sites and injection ages of suckling opossums. The results highlight the value of the opossum model as a natural in vivo system for investigating human cancer growth, metastasis and apoptosis at the cellular and molecular levels; enhancing identification of tumor associated antigens or T cell epitopes through use of humoral and cellular expres...
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A 10-month-old dog was presented with clinical signs of fever, lethargy, inappetence, and cardiac arrhythmias. Computed tomography scan and cerebrospinal fluid analysis supported the diagnosis of steroid-responsive meningitis-arteritis.... more
A 10-month-old dog was presented with clinical signs of fever, lethargy, inappetence, and cardiac arrhythmias. Computed tomography scan and cerebrospinal fluid analysis supported the diagnosis of steroid-responsive meningitis-arteritis. Echocardiography, electrocardiogram, and elevated serum troponin I supported a diagnosis of myocarditis. The arrhythmias resolved during treatment of the primary neurological disease, and they were considered as secondary to the meningitis.
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ABSTRACT In this study we present evidence to suggest that gastroduodenal mucosal defects may occur in gastric fistula dogs actively immunized with PGE2-thyroglobulin conjugate. One of four PGE2-immunized dogs developed a chronic... more
ABSTRACT In this study we present evidence to suggest that gastroduodenal mucosal defects may occur in gastric fistula dogs actively immunized with PGE2-thyroglobulin conjugate. One of four PGE2-immunized dogs developed a chronic pyloroduodenal ulcer with penetration into the pancreas and the other three had endoscopic evidence of gastric and/or duodenal erosions. In contrast, no gastroduodenal mucosal defects were seen in control dogs immunized with thyroglobulin alone. Occurrence of gastroduodenal ulcers or erosions was temporally related to formation of specific antibody to PGE2 suggesting that PGE2 antibody may be responsible for lesion formation. An increase in gastric acid secretion was not observed in PGE2-immunized dogs. Thus, it is likely that mucosal defects occur as a result of an impairment of PGE2-mediated mucosal defense mechanisms. Since gastroduodenal lesions can be visualized by endoscopy, the dog may prove to be useful in studying the role of endogenous PG in ulcer diseases.
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Our experience with shape memory polymers (SMP) began with a project to develop an embolic coil release actuator in 1996. This was the first known SMP device to enter human trials. Recent progress with the SMP devices include multiple... more
Our experience with shape memory polymers (SMP) began with a project to develop an embolic coil release actuator in 1996. This was the first known SMP device to enter human trials. Recent progress with the SMP devices include multiple device applications (stroke treatments, stents, other interventional devices), functional animal studies, synthesis and characterization of new SMP materials, in vivo and in vitro biocompatibility studies and device-tissue interactions for the laser, resistive, or magnetic-field activated actuators. We describe several of our applied SMP devices.
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ABSTRACT We demonstrated that simultaneous optical coherence tomography and fluorescence lifetime imaging microscopy imaging allows the identification of most types of coronary atherosclerotic plaques based on their... more
ABSTRACT We demonstrated that simultaneous optical coherence tomography and fluorescence lifetime imaging microscopy imaging allows the identification of most types of coronary atherosclerotic plaques based on their morphological/biochemical characterization.
... L ife tim e (n s ) N o rm . In t. ... 2. J. Siegel, DS Elson, SE Webb, KC Lee, A. Vlandas, GL Gambaruto, S. Leveque-Fort, MJ Lever, PJ Tadrous, GW Stamp, AL Wallace, A. Sandison, TF Watson, F. Alvarez, and PM French, "Studying... more
... L ife tim e (n s ) N o rm . In t. ... 2. J. Siegel, DS Elson, SE Webb, KC Lee, A. Vlandas, GL Gambaruto, S. Leveque-Fort, MJ Lever, PJ Tadrous, GW Stamp, AL Wallace, A. Sandison, TF Watson, F. Alvarez, and PM French, "Studying biological tissue with fluorescence lifetime imaging ...
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Chagas disease (Trypanosomiasis) is a cause of myocarditis in the southern United States causing cardiac conduction abnormalities, arrhythmias, and heart failure. To report clinical findings and outcome in Chagas positive (CP) dogs... more
Chagas disease (Trypanosomiasis) is a cause of myocarditis in the southern United States causing cardiac conduction abnormalities, arrhythmias, and heart failure. To report clinical findings and outcome in Chagas positive (CP) dogs requiring pacemaker implantation for bradyarrhythmias. One hundred and forty-four client-owned dogs requiring pacemaker implantation. Retrospective case series. Information regarding history, physical exam, laboratory and diagnostic imaging findings, treatment, and survival were obtained from medical records, with additional follow-up information obtained by contacting referring veterinarians and owners. Of the 144 dogs requiring pacemaker implantation from January 2001 to May 2010, 83 (57.6%) had a Chagas titer performed and 9 (10%) were CP. Concurrent ventricular arrhythmias (odds ratio 1.61, P = .005) or atrioventricular (AV) block (odds ratio 4.18, P < .001) increased the likelihood that a Chagas titer was submitted. Median age for CP dogs was 6.2 years (range, 0.3-10); 7 were male. Bradyarrhythmias included high-grade 2nd or 3rd degree AV block (n = 8) and sinus bradycardia with 1st degree AV block (n = 1); 5 had concurrent ventricular arrhythmias. A positive Chagas titer had a negative impact on survival (hazard ratio 4.04; 95% CI 1.36-12.1, P = .012) with a reported median survival time of 365 days (interquartile range, 84-973 days). Bradyarrhythmias can result in clinical signs requiring pacemaker implantation in CP dogs, and although the diagnosis negatively impacts survival, pacemaker therapy is a viable treatment option.
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Our experience with shape memory polymers (SMP) began with a project to develop an embolic coil release actuator in 1996. This was the first known SMP device to enter human trials. Recent progress with the SMP devices include multiple... more
Our experience with shape memory polymers (SMP) began with a project to develop an embolic coil release actuator in 1996. This was the first known SMP device to enter human trials. Recent progress with the SMP devices include multiple device applications (stroke treatments, stents, other interventional devices), functional animal studies, synthesis and characterization of new SMP materials, in vivo and in vitro biocompatibility studies and device-tissue interactions for the laser, resistive, or magnetic-field activated actuators. We describe several of our applied SMP devices.
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Growth of the vertebrate heart during embryonic and fetal life is characterized by hyperplasia of myocardial cells; these cells increase in number to a value characteristic for each species. Shortly after birth myocardial cells lose the... more
Growth of the vertebrate heart during embryonic and fetal life is characterized by hyperplasia of myocardial cells; these cells increase in number to a value characteristic for each species. Shortly after birth myocardial cells lose the capability of dividing, and further growth of the heart is due to myocardial cell hypertrophy and nonmuscle cell hyperplasia. This process, which is referred to as hypertrophic growth, results in a 30- to 40-fold increase in volume of individual myocardial cells during normal postnatal growth and maturation. The transition from hyperplastic to hypertrophic growth is related to formation of binucleated myocardial cells as a result of karyokinesis without cytokinesis. The molecular mechanism of this transition is uncertain. The response of the heart to increased metabolic demands or to an increased workload depends on the age of the animal at the time the stress is imposed. Increased myocardial workloads due to systemic hypertension, chronic hypoxia, o...
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A 10-month-old dog was presented with clinical signs of fever, lethargy, inappetence, and cardiac arrhythmias. Computed tomography scan and cerebrospinal fluid analysis supported the diagnosis of steroid-responsive meningitis-arteritis.... more
A 10-month-old dog was presented with clinical signs of fever, lethargy, inappetence, and cardiac arrhythmias. Computed tomography scan and cerebrospinal fluid analysis supported the diagnosis of steroid-responsive meningitis-arteritis. Echocardiography, electrocardiogram, and elevated serum troponin I supported a diagnosis of myocarditis. The arrhythmias resolved during treatment of the primary neurological disease, and they were considered as secondary to the meningitis.
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To assess endothelium-dependent responses of blood vessels in vitro, endothelial cells are removed by a variety of mechanical means. We sought to determine if the method of removal of the endothelium affected arachidonic acid metabolism... more
To assess endothelium-dependent responses of blood vessels in vitro, endothelial cells are removed by a variety of mechanical means. We sought to determine if the method of removal of the endothelium affected arachidonic acid metabolism and vascular reactivity of isolated strips of rabbit aorta. Thoracic aorta of New Zealand White rabbits were excised and sectioned into strips with a sharp razor blade. The luminal surface of the vessel was then gently stroked (denuded-1) or forcefully rubbed (denuded-2) with a moist cotton swab. Vessels were then either fixed in 3% glutaraldehyde and processed for electron microscopy, incubated with [14C]arachidonic acid and 20 microM A23187 for determination of arachidonic acid metabolism, incubated with 20 microM A23187 for measurement of endogenous release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and 12-hydroxyeicosatetraenoic acid (12-HETE) by specific radioimmunoassays, or suspended in an organ chamber filled with Krebs bicarbonate solution for vascular reactivity experiments. Electron micrographs showed that denuded-1 vessels lacked an endothelial cell layer and had slight degeneration of the smooth muscle cells. Additionally, these vessels had a diminished capacity to produce 6-keto-PGF1 alpha as compared to control vessels (214 +/- 25 vs. 360 +/- 36 pg/mg of tissue, P less than 0.05). Denuded-2 vessels contained severe degeneration and rupture of smooth muscle cells in addition to the loss of the endothelial cell layer. While the 6-keto-PGF1 alpha concentration (168 +/- 23 pg/mg) was less in denuded-2 vessels, HPLC indicated that the production of [14C]12-HETE was markedly increased in these vessels as compared to control or denuded-1 vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
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Background Platelet-derived growth factors help stimulate the neointimal proliferation of restenosis after coronary interventions. Reducing platelet accumulation at treated sites may attenuate restenosis. We tested this hypothesis by... more
Background Platelet-derived growth factors help stimulate the neointimal proliferation of restenosis after coronary interventions. Reducing platelet accumulation at treated sites may attenuate restenosis. We tested this hypothesis by inducing repetitive platelet aggregation at coronary angioplasty sites in dogs and measuring subsequent neointima formation. Methods and Results Cholesterol-sensitive dogs (n=74) received either 4% cholesterol-enriched diets for >8 months (n=29), creating visible atheromas, or normal canine diets (n=45). A coronary balloon angioplasty cyclic flow variation (CFV) model was used. One group of control dogs (group 1, n=8) had angioplasty with no arterial constriction applied and no drug treatment. Three other groups had arterial constrictors applied to provoke CFVs: group 2 (n=28) received no drug therapy, group 3 (n=18) received oral aspirin alone, and group 4 (n=20) received 3 oral antiplatelet agents: ridogrel, ketanserin, and clopidogrel (R+K+C) to s...
Research Interests: Dogs, Animals, Hypercholesterolemia, Blood Coagulation, Aspirin, and 15 moreClinical Sciences, Blood Flow, Group, Circulation, Drug Therapy, Coronary Circulation, Coronary Artery Disease, Bleeding Time, Blood Flow Velocity, Hematocrit, Drug treatment, Control Group, Coronary artery, Cardiovascular medicine and haematology, and Coronary Vessels
Adolescent Medicine Clinics, Volume 10, Issue 3, Pages 210-211, July 2009, Authors:Javier A. Jo; Brian E. Applegate; Fred Clubb.
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Investigations involving biopsies of human cardiac tissue often assume that myocardial samples from a specific location are representative of the entire heart. There are significant regional differences in gene expression in the heart. We... more
Investigations involving biopsies of human cardiac tissue often assume that myocardial samples from a specific location are representative of the entire heart. There are significant regional differences in gene expression in the heart. We used two models. In the first model, seven whole human hearts were cut in 1-cm slices from apex to base and 11 distinct regions were sampled. Full thickness left ventricular tissue was further subdivided equally into an inner, outer, and middle region. In the second model, hearts were removed from adult Sprague-Dawley rats and were divided into 4 regions. Using species-specific quantitative reverse transcriptase-polymerase chain reaction, we measured transcript levels of myosin heavy chain beta (MHC-beta), glucose transporter 1 (GLUT 1), and atrial natriuretic factor (ANF) in tissue samples from both models. In human heart, there were significant differences in transcript levels between regions. The following patterns could be recognized among the seven hearts. ANF expression was highest in the subendocardial region. MHC-beta and GLUT 1 transcript levels were higher in the right ventricle than the left ventricle. As expected, ANF transcript levels were highest in the atria, where MHC-beta and GLUT 1 expression was low. Analogous to the human studies, MHC-beta and GLUT 1 transcript levels were low in rat atria as compared to ventricles. In rat heart, MHC-beta expression was higher in the left ventricle than the right ventricle while GLUT 1 expression was not significantly different between ventricles. Despite the large variability in transcript levels among different regions in human hearts, certain patterns in gene expression emerged suggesting that different anatomical regions of the heart also differ in respect to gene expression.
Research Interests: Cardiology, Adolescent, Gene expression, Humans, Female, and 15 moreAnimals, Male, Aged, Glucose Transport, Rats, Adult, Genetic variation, Heart Ventricles, Left Ventricle, Gene expression profiling, Atrial Natriuretic Factor, genetic heterogeneity, Left Ventricular, Regional Difference, and Cardiovascular medicine and haematology
Adolescent Medicine Clinics, Volume 10, Issue 3, Pages 210-211, July 2009, Authors:Javier A. Jo; Brian E. Applegate; Fred Clubb.
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Background: Investigations involving biopsies of human cardiac tissue often assume that myocardial samples from a specific location are representative of the entire heart. Hypothesis: There are significant regional differences in gene... more
Background: Investigations involving biopsies of human cardiac tissue often assume that myocardial samples from a specific location are representative of the entire heart. Hypothesis: There are significant regional differences in gene expression in the heart. Methods: We used two ...
Research Interests: Cardiology, Adolescent, Gene expression, Humans, Female, and 15 moreAnimals, Male, Aged, Glucose Transport, Rats, Adult, Genetic variation, Heart Ventricles, Left Ventricle, Gene expression profiling, Atrial Natriuretic Factor, genetic heterogeneity, Left Ventricular, Regional Difference, and Cardiovascular medicine and haematology
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To determine whether texturing and coating have additive effects in promoting tissue integration and inhibiting fibrosis, we evaluated smooth silicone rubber (SSR), textured silicone rubber (TSR), porous silicone rubber (PSR), expanded... more
To determine whether texturing and coating have additive effects in promoting tissue integration and inhibiting fibrosis, we evaluated smooth silicone rubber (SSR), textured silicone rubber (TSR), porous silicone rubber (PSR), expanded polytetrafluoroethylene (ePTFE), and porous polyurethane (PPU) subcutaneous implants in eight minipigs. Some of the implants were coated with type IV collagen (Col) and/or fibronectin (Fn). At 6 months, we removed the implants and examined them microscopically. Texturing was more important than Col and Fn in reducing fibrosis and inflammation. The PSR yielded the best response, including reduced fibrosis and inflammation, satisfactory adherence, and no dystrophic mineralization.
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A method has been developed to enhance the albumin affinity of a number of medical polymers, based on alkylation of the surface with straight-chain 16- or 18-carbon alkyl groups. This method has been demonstrated to induce the rapid... more
A method has been developed to enhance the albumin affinity of a number of medical polymers, based on alkylation of the surface with straight-chain 16- or 18-carbon alkyl groups. This method has been demonstrated to induce the rapid binding of albumin from single and binary protein solutions, from plasma, and apparently, from whole blood. The bound albumin resists fluid shear or chemically induced desorption. Fibrinogen adsorption is inhibited in vitro and in vivo. Complement protein C3 activation from plasma is inhibited. Fibrin formation and platelet aggregation is inhibited in short-term in vivo experiments. Long-term catheter implant studies suggest that the C18 alkylation is more effective than most, if not all, currently available treatments for the retention of a clean, biocompatible, blood-contacting surface. No data have been obtained to date that conflict with the hypothesis that a renewable albumin layer, so formed, blocks the adsorption or conformational alteration of plasma proteins that otherwise might initiate or participate in various host defenses.