bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Situations and Results of Cardiopulmonary Support by Peripheral Access for Resuscitation and Recovery
Authors: Montiès J.R. , Caus T. , Mesana T. , Pomane C. , Mouly‐Bandini A. , Guez P.
Published: November 2008

Abstract: Use of cardiopulmonary support (CPS) by peripheral access with a membrane oxygenator has made considerable progress as a result of the development of centrifugal pumps, percutaneous cannulation, and pre‐heparinized circuits. We have used CPS for resuscitation in 3 cases, for recovery after cardiotomy in 6 cases (myo‐cardial insufficiency, 4; pulmonary arterial hypertension, 1; respiratory insufficiency, 1), and after heart transplantation in 1 case. Of these 10 patients, 3 died during CPS, 5 were successfully weaned, and 2 underwent heart transplantation. Use of CPS is expanding for emergency cardiac assistance. Installation is simple and rapid. It allows recovery of organs pending more invasive and costly techniques.
Clinical Experience with BioMedicus Centrifugal Ventricular Support in 172 Patients
Authors: Noon George P. , Ball James W. , Papaconstantinou Harry T.
Published: November 2008

Abstract: One hundred and seventy‐two patients at The Methodist Hospital in Houston, Texas, were placed on BioMedicus centrifugal ventricular support. One hundred thirty‐nine patients were male and 33 were female with a mean age of 59.7 years. Reasons for support were post‐cardiotomy cardiac failure (129 patients), cardiac allograft failure (17 patients), bridge to transplantation (10 patients), resuscitation (7 patients), postpercutaneous trans‐luminal coronary angioplasty emergent (2 patients), and other (7 patients). Support was by left ventricular assist device in 108 patients, right ventricular assist device in 20 patients, and biventricular assist device in 44 patients. Eighty‐four patients (48.8%) were weaned from the ventricular assist device, and 88 patients (51.2%) were not weaned. Thirty‐four patients (20.0%) were discharged from the hospital. Complications included coagulopathy, renal insufficiency/failure, respiratory insufficiency/ failure, neurological deficits, sepsis, arrhythmias, and device‐related complications. Overall causes of death were ventricular failure (55.1%), triage (13.0%), arrhythmias (9.4%), graft failure (5.9%), coagulopathy (4.3%), sepsis syndrome (2.9%), device‐related (0.7%), and other (0.7%). BioMedicus centrifugal ventricular support can be implemented rapidly and easily. Device‐related complications are few (1.2%), and it is relatively inexpensive when compared with other ventricular assist systems. This series demonstrates that a substantial number of patients may benefit from temporary centrifugal ventricular support.
Function and Metabolism of Brain Synaptosomes in Chronic Renal Failure
Authors: Smogorzewski Miroslaw , Ni Zhenmin , Massry Shaul G.
Published: November 2008

Abstract: Patients with advanced renal failure have derangements in the function of their nervous system. The available clinical and experimental data indicate that the state of the secondary hyperparathyroidism of renal failure plays a major role in the genesis of the nervous system dysfunction. The excess parathyroid hormone (PTH) mediates its deleterious effect by causing an elevation in cytosolic calcium of brain cells. This report reviews the evidence leading to the conclusion that PTH is a major uremic toxin.
Evaluation of the Antithrombogenicity of a New Microdomain Structured Copolymer
Authors: Kawahito Koji , Tasai Kimitaka , Murata Seiichiro , Yamaguchi Atsushi , Mizuhara Akihiro , Adachi Hideo , Ino Takashi
Published: November 2008

Abstract: A new antithrombogenic material was studied, fluorine‐acryl‐styrene‐urethane‐silicone (FASUS) copolymer, the theoretical basis of which attributed to its hydrophilic and hydrophobic microdomain structure. In this series of experiments, the blood compatibility of this copolymer was evaluated in vitro and ex vivo. For the in vitro evaluation, a whole blood clotting test and the mi‐crosphere column test were performed. For the ex vivo evaluation, two series of shunt tests in rabbits were performed, one was the arterioartery (A‐A) shunt model, and the other was the arteriovenous (A‐V) shunt model. The antithrombogenicity was assessed by measuring the shunt obstructive time in the A‐A shunt experiment. The A‐V shunt experiment was assessed by measuring the circulating platelet counts, platelet aggregability, activated partial thromboplastin time (APTT), and prothrombin time (PT). In the whole blood clotting test, FASUS revealed the significantly longer blood clotting time than that of the control glass tubings (19.7 ± 1.0 versus 6.5 ± 0.7 min, p < 0.001). In the microsphere column test, the coated group had a 30% reduction of the platelet number in the eluted blood in contrast with a marked decrease of 70% in the control group (p < 0.05). In the ex vivo A‐A shunt experiment, the occlusion time for the FASUS‐coated group was significantly longer than that of the control (109.7 ± 17.3 versus 3.0 ± 0.4 min, p < 0.05). The A‐V shunt experiment showed that the FASUS copolymer suppressed the decrease in platelet counts and tended to improve prolonged APTT compared with that of the control. Clinically, in 25 patients, we placed coated FASUS copolymer into the cannulas for use in percutaneous cardiopulmonary support (PCPS) procedures. There was no evidence of thrombus on the blood contacting surface and no thromboembolism in major organs clinically or upon postmortem examination. In summary, this new copolymer may be effective in preventing thrombus formation in vitro, ex vivo, and in clinical situations.
Development of an Isolated Perfusion Circuit with Double Bypass Using Automatic Blood Pumps
Authors: Ito Fujio , Seo Takahiko , Ito Takahiro , Umeda Takashi , Ando Hisami , Takagi Hiroyuki
Published: November 2008

Abstract: Isolated perfusion of the liver is a useful and promising therapeutic method for various hepatic diseases. However, conventional techniques using a roller pump require a large priming volume and cannot run at the low flow rate without complications. These disadvantages do not allow the use of conventional techniques in smaller pediatric patients. The authors solved these problems successfully for the first time by using unique sac‐type air‐driven automatic blood pumps with an oxygen‐ator primed with a blood volume of 65 ml in the total circuit. The usefulness of these blood pumps for liver perfusion was evaluated in small animals weighing 3.5–6.0 kg. A hepatic perfusion circuit was established between the portal vein and the inferior vena cava. The blood pumps worked well without any trouble, and stable flow could be maintained. No hepatocellular damage or anaerobiosis of the liver was observed at a hepatic perfusion flow rate of 20 ml/min/kg. Isolated liver perfusion using these blood pumps can be applied in infants and young children.
A Potential Soft Tissue Filling Material: Chloramphenicol Loaded Poly(D, L–Lactide) Sponges
Authors: Kozluca Ahmet , Denkbaş Emir B. , Pişkin Erhan
Published: November 2008

Abstract: Poly(D, L–lactide) (PDLLA) homopolymers were produced by the ring opening polymerization of a D, L–lactide dimer by using stannous chloride as the catalyst. Chloramphenicol loaded PDLLA sponges were prepared by a solvent evaporation procedure by using the PDLLA homopolymers with three different molecular weights (i. e., 11, 000, 20, 000 and 35, 000 daltons). Chloramphenicol loading was changed by using three different solvents (i. e., acetone, ethyl acetate, and acetonitrile) and by changing the initial polymer concentration and its molecular weight and the initial concentration of the drug. Higher degradation rates of the chloramphenicol loaded PDLLA sponges in alkaline pH 9. 0 and at 37°C were observed. Chloramphenicol release rates were also high at these conditions. It was concluded that chloramphenicol release was both degradation and diffusion controlled.
Right Ventricular Failure in Patients Requiring Left Ventricular Assistance
Authors: Cooper G. J. , Withington P. S. , Wood A. J. , Magee P. G. , Lewis C. T. , Graham T. R.
Published: November 2008

Abstract: Right ventricular failure may complicate isolated left ventricular assistance. In a series of 8 patients undergoing left ventricular assistance in postcardiotomy cardiogenic shock, right ventricular failure developed in 5, directly contributing to death in all cases despite initially satisfactory support. Difficulty in grafting a dominant right coronary artery was a common factor in all cases. Early consideration should be given to biventricular support under these circumstances.
Potential Hazards of Deionization Systems Used for Water Purification in Hemodialysis
Authors: Bland Lee A. , Arnow Paul M. , Arduino Matthew J. , Bova Judy , McAllister Sigrid K.
Published: November 2008

Abstract: This study was conducted to determine the efflux of specific ions, including fluoride, from a deionization (DI) water purification system (WPS) when the WPS was operated beyond exhaustion of the DI resin. Effluent from the DI WPS was monitored for resistivity, total dissolved solids, pH, and concentrations of silica, fluoride, potassium, and sodium. After 16,000 L of water was purified, the resistivity declined to 0.492 Ω Ohm‐cm, and silica was released from the DI WPS. Fluoride ions were released after an additional 8,000 L water was treated, and the resistivity fell to 0.07 Ω Ohm‐cm. The fluoride efflux reached a peak of 32 mg/L, 28 times greater than the original fluoride concentration in the city water. Sodium and potassium ions were released after approximately 26,000 and 32,000 L of water had been treated and reached peaks of 76 and 47 mg/L, respectively. This study confirms that the minimum resistivity standard of 1 Ω Ohm‐cm for DI water used for hemodialysis should provide an adequate safety margin. Once resistivity fell to 1 Ω Ohm‐cm, more than 8,000 L of water was treated before fluoride efflux occurred. Accordingly, hemodialysis centers should be attentive to the calculated capacity of their DI WPS and reliably monitor the resistivity to prevent patient illness related to exhaustion of DI resins.
Modulation of Idiotypic and Antiidiotypic Immunoglobulin G Responses in an Alloimmune Thrombocytopenic Patient Associated with Extracorporeal Protein A Immunoadsorption
Authors: Balint Joseph P. , Hussein Mohamad A. , Quagliata Franco , Cochran Sharon , Jones Frank R.
Published: November 2008

Abstract: In the present case study, a patient with Non‐Hodgkins Lymphoma underwent combination chemotherapy resulting in severe pancytopenia requiring transfusion support with blood products. The patient became refractory to random donor platelet transfusions and subsequently received five immunoadsorption treatments. The patient's clinical response to immunoadsorption therapy was assessed by monitoring platelet transfusion recovery and survival. In addition, changes in antibody responses were assessed. Early during the course of immunoadsorption therapy, antiplatelet immunoglobulin G (IgG) alloantibody was detected. There was a decline in antiplatelet IgG alloantibody levels by the last immunoadsorption treatment associated with increases in platelet corrected count increments after completion of immunoadsorption therapy. In addition, elevated levels of antiidiotypic IgG antibody detected early during the course of therapy were significantly reduced by the last immunoadsorption treatment. This case study suggests that specific alloimmune idiotypic IgG antibody and corresponding antiidiotypic IgG antibody responses may be modulated in association with extracorporeal immunoadsorption employing protein A/silica columns.
Physiologic Control of Cardiac Assist Devices
Authors: Hall Alden W. , Soykan Orhan , Harken Alden H.
Published: November 2008

Abstract: Total artificial hearts (TAHs) and biventricular assist devices (BVADs) have varying levels of acceptance and reliability, and the research on both focuses on their control mechanisms. Efforts generally aim to achieve a response to physiologic demand and left/right output balance, and beneficial cardiac output (CO) and effective control mechanisms have been achieved by eliciting a Starling‐like response to preload and afterload. Such control mechanisms, however, generally base device output on a single parameter, such as the preload on the heart. Current TAHs and BVADs provide relatively fixed oxygen delivery to patients with large physiologically induced variations in oxygen consumption. This paper aims to document fluctuations in oxygen consumption that are normal in BVAD and TAH patients, identify a number of patient‐generated signals that reflect these fluctuations, and describe a multitiered control algorithm based upon these signals. Such a control system may offer better response times and more physiologic cardiac outputs. There currently exists a microprocessor‐based control mechanism that can be adapted to control TAHs and BVADs using input from a variety of sensors, and it can be found in modern implantable pulse generators (IPGs). Today's pacemakers are capable of rate control and can run diagnostic programs and store data that could be valuable in the evaluation of the patient's condition.
Development of a Centrifugal Pump with Improved Antithrombogenicity and Hemolytic Property for Chronic Circulatory Support
Authors: Taenaka Yoshiyuki , Wakisaka Yoshinari , Masuzawa Toru , Tatsumi Eisuke , Toda Koichi , Miyazaki Koji , Eya Kazuhiro , Baba Yuzo , Nakatani Takeshi , Ohno Takashi , Nishimura Takashi , Takano Hisateru
Published: November 2008

Abstract A centrifugal pump with a unique structure has been developed for chronic support. The pump is driven by a magnetic coupling and has no rotating shaft, no seal around the rotating part, and a balancing hole at the center of the impeller and the thrust bearing. The pump was improved in stepwise fashion to realize good antithrombogenicity and low hemolysis. The first pump, the National Cardiovascular Center (NCVC)‐O, had an impeller with 4 rectangular and curved vanes; 6 triangularly shaped curved vanes were employed in the second model, the NCVC‐1, to reduce trauma to the blood. In the third design, the NCVC‐2, the central hole was enlarged, and the thrust bearing shoulder was rounded so that blood washing was enhanced around the impeller; stream lines also were smoothed for improved antithrombogenicity. The hemolytic property of the device was evaluated in vitro with heparinized fresh goat blood; hemolysis indexes of the NCVC‐0, ‐1, and ‐2 were 0.05, 0.01, and 0.006 g per 100 L, respectively. Antithrombogenicity of the pumps was examined in animal experiments as a left heart bypass device in goats weighing 52–75 kg. Six NCVC‐0 pumps were driven for 14 to 33 (22.0 ± 7.6) days in goats receiving the antiplatelet drug cilostazol orally. Four NCVC‐I pumps ran for 1 to 80 (28.5 ± 30.6) days with the same drug regimen in 2 cases and with no anticoagulation therapy in 2 cases. After 3 preliminary 1‐week tests of NCVC‐2 pumps in animals, the pump was installed in 3 goats; 2 pumps were still running on the 182nd and 58th pumping day. Intracorporeal implantation also was attempted successfully. The results indicate that this pump has promising features for chronic support although longer term and additional evaluations are necessary.
Using Hybrid Magnetic Bearings to Completely Suspend the Impeller of a Ventricular Assist Device
Authors: Khanwilkar Pratap , Olsen Don , Bearnson Gill , Allaire Paul , Maslen Eric , Flack Ron , Long James
Published: November 2008

Abstract Clinically available blood pumps and those under development suffer from poor mechanical reliability and poor biocompatibility related to anatomic fit, hemolysis, and thrombosis. To alleviate these problems concurrently in a long‐term device is a substantial challenge. Based on testing the performance of a prototype, and on our judgment of desired characteristics, we have configured an innovative ventricular assist device, the CF‐VAD4, for long‐term use. The design process and its outcome, the CFVAD4 system configuration, is described. To provide unprecedented reliability and biocompatibility, magnetic bearings completely suspend the rotating pump impeller. The CFVAD4 uses a combination of passive (permanent) and active (electric) magnetic bearings, a mixed flow impeller, and a slotless 3‐phase brushless DC motor. These components are shaped, oriented, and integrated to provide a compact, implantable, pancake‐shaped unit for placement in the left upper abdominal quadrant of adult humans.
Transcutaneous Energy Transfer with Voltage Regulation for Rotary Blood Pumps
Authors: Mussivand Tofy , Holmes Kevin S. , Hum Albert , Keon W.J.
Published: November 2008

Abstract Rotary blood pumps often require a constant operating voltage. To meet this requirement and to eliminate the need for percutaneous leads, a voltage‐regulated transcutaneous energy transfer (TET) system has been developed. Voltage regulation is achieved by using a transcutaneous infrared feedback control loop operating on a 890 nanometer (nm) wavelength. In vitro testing of the system developed has shown that output voltage can be maintained to within 0.2 V of nominal (14.5 V) for delivered powers up to 50 watts (W) and coil separations of between 3 and 10 mm. Power transfer efficiencies were determined to be from 68% to 72% over the tested range of coil separations and output currents from 1.5 to 3.6 amperes (A). This system has demonstrated acceptable performance in regulating output voltage while transferring power inductively without using percutaneous connections. By integrating this type of TET system with an implanted rotary blood pump, the quality of life for the device recipient could be improved.
Effect of Pulsatile and Nonpulsatile Assist on Heart and Kidney Microcirculation with Cardiogenic Shock
Authors: Nakata Kin‐ichi , Shiono Motomi , Orime Yukihiko , Hata Mitumasa , Sezai Akira , Saitoh Toshimi , Sezai Yukiyasu
Published: November 2008

Abstract: To estimate microcirculation of the heart and kidney in pulsatile and nonpulsatile‐assisted circulation, a comparison study was done using a swine model. Acute myocardial infarction was made by ligation of the left coronary artery branches. After cardiogenic shock, animals were divided into 3 groups as follows: Group C (n = 6), no assist provided; Group NP (n = 6), assisted by a nonpulsatile pump (Bio‐Medicus BP‐80); Group P (n = 6), supported by a pulsatile pump (Nippon Zeon). Left coronary artery flow, endocardial and epicardial regional flows, and renal cortex and medulla tissue blood flows were measured. Left coronary artery flow and endocardial and epicardial tissue blood flows decreased in cardiogenic shock, and they recovered to the control level soon after support in both Group N and Group P. Renal medulla and cortex tissue blood flows decreased in cardiogenic shock, and these flows did not recover in either Group N or P. However, cortex blood flow in Group P did improve, but it did not improve in Group N. These results suggested that pulsatile assist was more effective than nonpulsatile assist for microcirculation after cardiogenic shock to avoid deterioration of major organ functions.
Basic Performance of a Miniature Intraventricular Axial Pump
Authors: Umezu Mitsuo , Ohtake Yasuo , Sakata Koji , Fujimoto Tetsuo , Yamazaki Kenji , Koyanagi Hitoshi , Iiyama Haruo , Mori Toshio , Higuchi Kenji
Published: November 2008

Abstract: A miniature intraventricular axial pump for left ventricular (LV) support is under development. This pump was designed for placement in the LV cavity by insertion through the LV apex with the outlet located at the ascending aorta via the aortic valve. The basic hydro‐dynamic characteristics represented as a relationship between pump head (H) and flow (Q) showed a negative linear relationship under a constant head. This characteristic was generally the same as that obtained by other axial rotation pumps. However, the actual H‐Q relationship was represented as anticlockwise “loops” caused by the contraction of the natural LV. The comparative in vitro data on these H‐Q loops showed that the shape of the loops was changed drastically by the connecting condition between the pump and natural cardiovascular system.
Extracorporeal Membrane Oxygenation as a Bridge to Cardiac Transplantation in Children
Authors: Ishino Kozo , Weng Yuguo , Alexi‐Meskishvili Vladimir , Loebe Matthias , Uhlemann Frank , Lange Peter E. , Hetzer Roland
Published: November 2008

Abstract: The feasibility and efficacy of extracorporeal membrane oxygenation (ECMO) as a bridge to cardiac transplantation was examined in 6 pediatric patients who suffered irreversible myocardial failure after undergoing surgery for congenital heart defects. The mean time of ECMO support was 260.5 h, range, 101–402 h. Three patients underwent transplantation, 2 of whom are long‐term survivors. Progressive hypotension as a result of capillary leak syndrome precluded further ECMO support in the other 3 patients. Overall, 2 of the 6 patients survived. Major complications were encountered in 4 patients including bleeding in 2, a seizure in 1, and renal failure in 3, 2 of whom recovered renal function after transplantation. Infection did not occur in any of the 6 patients. Exchanging ECMO components was performed with no difficulties; these exchanges included a centrifugal pump once for 2 patients and a membrane oxygenator once for 3 patients. Our results indicate that ECMO can safely keep critically ill pediatric transplant candidates alive for more than 1 week with a low incidence of multiple organ failure.
Molecular Biology of Cytokines
Authors: Dendorfer Ulrich
Published: November 2008

Abstract: The development of the technological armamentarium of molecular biology has revolutionized biomedical research in general and nephrologic investigation in particular. In addition to the recent identification of several genes involved in normal kidney function and pathologic conditions, our knowledge regarding the role of cytokines in primary renal diseases, transplant rejection, and dialysis effects has expanded greatly. In particular, molecular biologic methodology has provided insight into the mechanisms controlling cytokine gene regulation, which occurs primarily at the transcriptional level and is mediated by DNA‐binding proteins interacting with specific recognition motifs in genetic promoter and enhancer elements. Interleukin‐6 (IL‐6) is discussed as an example because it is a secretory product of mesangial cells and participates in the cytokine network that determines glomerular and interstitial inflammation. In our analysis of IL‐6 gene regulation employing reporter gene and electrophoretic mobility shift assays, we have found that bacterial lipopolysaccharide and cyclic adenosine monophosphate synergistically induce IL‐6 expression in macrophages through at least four transcription factors, including AP‐1, cAMP‐responsive element‐binding protein (CREB), NF‐IL6, and NF‐KB. One of the most exciting areas of future research will focus on transcription factor activation in experimental and clinical disease states. Novel therapeutic approaches targeting transcriptional regulation are currently being explored.
Changes in Polyurethane Calcification Due to Antibiotics
Authors: Chandy Thomas , Vasudev Sindhu C. , Sharma Chandra P.
Published: November 2008

Abstract: To develop artificial materials for prolonged use in the vascular system, the complicated process of surface‐induced calcification must be better understood. Calcification was examined on porous polyurethane incubated in metastable solutions of calcium phosphate, and the role of certain antibiotics in the medium was evaluated. It seems that certain aminoglycoside antibiotics can modify polyurethane surfaces and, subsequently, their mineralization process. In addition, these antibiotics may alter the calcium transport through polyurethanes. Therefore, it is conceivable that certain antibiotics can, in addition to producing their antibacterial effect, modulate surface calcium binding by changing the calcium mobilization and crystallization. Additional studies are needed to develop applications.
Clinical Strategies in Intravascular Gas Exchange
Authors: Sim Kenneth M. , Evans Timothy W. , Keogh Brian F.
Published: November 2008

Abstract: Specific therapies in the management of acute pulmonary failure remain elusive, with attention being focused instead on novel supportive measures. The benefits of extracorporeal gas exchange support remain uncertain, and the perceived simplicity of intravascular gas exchange has, therefore, attracted much interest. Initial clinical experience with the intravascular oxygenator (IVOX) device confirms its safety and simplicity, but estimated mean gas‐transfer values represent only 25% of basal gas‐exchange requirements. The inherent limitations of IVOX as an oxygenator are discussed, providing a rationale for considering IVOX as primarily a CO, removal device. Reappraisal of the clinical place of intravascular gas exchange and the identification of specific applications most likely to yield benefit to patients are suggested. Design modifications enhancing efficacy are anticipated, further strengthening the potential of intravascular gas‐exchange devices in selected patients with pulmonary failure.
Safety Margin of Magnetic Coupling Distance in Decoupling of a Pivot Bearing‐Supported Gyro Centrifugal Pump (C1E3)
Authors: Takami Yoshiyuki , Nakazawa Tadashi , Makinouchi Kenzo , Glueck Julie , Benkowski Robert , Nosé Yukihiko
Published: November 2008

Abstract: The pivot bearing‐supported Gyro C1E3 centrifugal pump is driven by magnetic coupling. The magnetic coupling distance (MCD) between the impeller magnet and the driver magnet affects both hydraulic performance and hemolysis. Although a greater MCD causes less hemolysis, it increases the risk of decoupling of the impeller magnet. Therefore, it is important to consider the effect of the MCD on both hemolysis and decoupling when the C1E3 pump is applied in various circulatory assist conditions. This study investigates the effect of the MCD on decoupling in a C1E3 pump that is driven by the Nd‐Fe‐B composite ring‐shaped magnets. The results will determine which MCD is the most practical in all assist device conditions. The MCD of the C1E3 pump was varied from 9.5 to 14.5 mm by inserting spacers between the bottom pump housing and the driver magnet. At a rotational speed just before the decoupling occurred, the flow rate and total pressure head were measured. The results revealed that a MCD between 9.5 and 14.5 mm was enough to produce a flow rate of more than 10 L/min without decoupling, and a MCD of less than 11.5 mm was required when the total pressure head was more than 500 mm Hg. Thus, the limiting factor for the MCD of the C1E3 pump is the total pressure head rather than the flow rate. An MCD of less than 11.5 mm is required to prevent decoupling of the impeller of the C1E3 pump with the specific Nd‐Fe‐B magnets in the full range of clinical circulatory assist conditions.
Specific Regulation of Gene Expression by Antisense Nucleic Acids: A Summary of Methodologies and Associated Problems
Authors: Kawasaki Hiroaki , Machida Meiji , Komatsu Masaaki , Li Hai‐Ou , Murata Takehide , Tsutsui Hatsumi , Fujita Akiko , Matsumura Masatoshi , Kobayashi Yoshiro , Taira Kazunari , Yokoyama Kazunari K.
Published: November 2008

Abstract: Gene therapy based on gene‐specific nucleic acids has moved from theory to a practical possibility in a very short time. The new DNA and RNA therapeutic reagents are intended to stop the growth of cancerous cells or the production of viruses. At the practical level, the efficacy of antisense oligomers as therapeutic reagents has been carefully examined in various clinical contexts. For the efficient use of antisense nucleic acids as pharmaceutical agents, a complete analysis of their mechanisms of action is necessary. The use of antisense oligomers always involves the following problems: base‐pair specificity, stereoisomer specificity, stability and resistance to nucleases of sense‐antisense duplexes, permeability of the cell membrane and targeting of the oligomer, safety, and the preparation of large amounts of oligomer. Herein, we review the basic concepts and problems associated with the exploitation of antisense technology. We have identified a new transcription factor triple‐helix‐binding zinc‐finger protein‐1 (THZif‐1) induced by antisense c‐myc RNA in the antisense‐transformed HL60 cells. The encoded protein functions as the repressor of c‐myc to achieve the reduction of the endogenous expression of c‐myc gene. Therefore, the introduction of THZif‐1 gene into HL60 cells in conjunction with antisense c‐myc oligomers may result in the efficient repression of the expression of the c‐myc gene. The molecular features of this factor are herein discussed.
Immune Modulation Associated with Extracorporeal Immunoadsorption Treatments Utilizing Protein A/Silica Columns
Authors: Balint Joseph P.
Published: November 2008

Abstract: The Prosorba column is designed for the removal of IgG and IgG containing immune complexes from plasma. Clinical studies employing patients presenting with idiopathic thrombocytopenic purpura (ITP) indicate that this new form of therapy is effective in approximately 40% of treated patients. Responding patients exhibit a significant increase in platelet numbers associated with decreases in antiplatelet antibody and immune complexes suggesting the induction of immune modulation. Preliminary studies indicate that ITP patients presenting with antiplatelet IgG antibody are those most likely to respond. In addition, this subgroup of ITP patients also exhibit elevated levels of antiidiotypic IgG antibody, which may contribute to an exacerbation of the autoimmune process due to antigen mimicry of the platelet autoantigen. Interestingly, antiidiotypic IgG antibody levels appear to decrease in association with antiplatelet IgG autoantibody levels suggesting that removal of immune complexes composed of IgG autoantibody and platelet autoantigen and/or antiidiotypic IgG antibody may be related to the observed clinical responses. Additional studies with alloimmune patients refractory to platelet transfusion suggest that transfused platelet retention time may be increased as a consequence of immunoadsorption therapy. This clinical response appears to be related to decreases in IgG alloantibody, again suggesting the induction of immune modulation. Alloimmune thrombocytopenic patients also appear to present with elevated levels of antiidiotypic IgG antibody which may contribute to an exacerbation of the alloimmune process due to antigen mimicry of platelet alloantigen(s). Preliminary studies indicate that both IgG alloantibody and corresponding antiidiotypic IgG antibody levels appear to decrease during immunoadsorption therapy, which suggests that removal of these antibodies, possibly in the form of immune complexes, may be related to clinical responses. Finally, studies in rheumatoid arthritis patients suggest that immunoadsorption therapy may be of clinical benefit in this autoimmune disorder. Consistent with the results observed above, preliminary studies in patients responding to immunoadsorption treatments again suggest that there is a concomitant decrease in idiotypic IgG (rheumatoid factor) and antiidiotypic IgG antibodies levels during therapy.
Development of Selective Low‐Density Lipoprotein (LDL) Apheresis System: Immobilized Polyanion as LDL‐Specific Adsorption for LDL Apheresis System
Authors: Tani Nobutaka
Published: November 2008

Abstract: Low‐density lipoprotein (LDL) is widely recognized as one of the major risk factors for developing coronary heart diseases. Despite intensive development of LDL‐lowering drugs, there still exist those patients with refractory hyperlipidemia whose plasma LDL levels are not sufficiently lowered by drugs. LDL apheresis, direct removal of plasma LDL from circulating blood, is thought to be the most promising treatment for such refractory patients. Various techniques, such as the use of an im‐munoadsorbent utilizing an anti‐LDL antibody, have been used in an attempt to achieve the selective removal of LDL. However, none were widely used because of complications, poor selectivity, and so forth. To establish a safe and effective LDL apheresis system, we chose a synthetic affinity adsorbent as the LDL‐removing device. Synthetic polyanion compounds were used as the affinity ligands for LDL adsorbent to simulate the anion‐rich sequence of LDL binding sites in the human LDL receptor. Among various polyanion compounds, those polyanions with sulfate or sulfonate groups and hydrophilic backbone were found to have strong affinity for LDL. In contrast, polyanions with carboxyl groups showed poor affinity. Dextran sulfate (DS) was selected as the affinity ligand of LDL adsorbent for its high affinity and low toxicity. The influence of its charge density and molecular weight on its affinity for LDL was suitable. The affinity rapidly increased as the charge density increased, then, reached a constant value. Little affinity was found for either the DS monomer (glucose sulfate) or DS with a molecular weight higher than 104 daltons whereas DS with molecular weights in the midrange showed strong affinity. DS with a midrange molecular weight was immobilized on cellulose hard gel to give LDL adsorbent clinical application. The adsorbent demonstrated an excellent selectivity for LDL and very low density lipoprotein (VLDL) in vitro. Adsorption of high‐density lipoprotein and major plasma proteins was almost negligible. Additional study of the LDL‐binding mechanism revealed that DS directly interacts with positively charged sites on LDL, which demonstrates that the nature of the interaction is the same as that of LDL receptor. An LDL adsorption column (Liposorber) packed with an LDL adsorbent and polysulfone hollow‐fiber plasma separator (Sulflux) was developed as an efficient LDL apheresis system. Clinical investigation proved that this system is capable of intensively lowering the plasma LDL level without affecting major plasma components.
Thyroplasty Type I with Ceramic Shim
Authors: Sakai Noboru , Nishizawa Noriko , Matsushima Jun‐ichi , Kurihara Hideo , Kokubun Takehiko , Koichi Ken‐ichi , Maguchi Shiroh , Inuyama Yukio
Published: November 2008

Abstract: To prevent side effects from a silicone shim in Isshiki thyroplasty type I, we used a ceramic shim in 10 patients with unilateral recurrent laryngeal nerve paralysis. No published reports have described the use of ceramic in this type of surgery. According to the degree of glottic insufficiency, ceramic shims of various heights were inserted into the fenestration made in the thyroid ala. All patients experienced subjective improvement of voice postoperatively. Laryngoscopies in most cases showed that glottic insufficiency improved postoperatively. In the postoperative examination, the maximum phonation time improved an average of 3.7 s, and the mean flow rate improved an average of 331 ml/s. We have analyzed the relationship of these improvements to the degree of glottic insufficiency and have compared our results with those of other investigators.
Management of Acute Fulminant Myocarditis Using Circulatory Support Systems
Authors: Reiss Nils , El‐Banayosy Ali , Posival Herbert , Morshuis Michiel , Minami Kazutomo , Korfer Reiner
Published: November 2008

Abstract: Although the natural history of acute myocarditis leads to complete recovery in the majority of patients, rapid and irreversible cardiac decompensation resulting in death is known to occur. One possible therapy to improve the poor prognosis of this patient group may be the implantation of circulatory support systems that allow myocardial recovery or bridging to heart transplantation. Therapeutic protocols have been suggested, but clinical experiences in this area are few. In this paper we report on our clinical experiences in cardiogenic shock after acute fulminant myocarditis using different types of circulatory support systems. Three different systems were used: a biomedicus centrifugal pump as a ventricular assist device (VAD) or femoro‐femoral bypass (FFB) including oxygenator; Abiomed BVS 5000, and Thoratec ventricular assist device. Hemodynamic criteria for implantation of support systems were cardiac index < 2.0 L/min/m2. SVR = 1000 dyne‐s‐cm‐5 central venous pressure (CVP) or left atrial pressure (LAP) > 20 mm Hg, and urine output < 20 ml/h despite maximal pharmacological therapy. Age total of 5 patients (mean age 29 years, range 15–55 years) in cardiogenic shock after acute fulminant myocarditis were included. Two patients initially were supported for stabilization and transportation from an outside hospital by FFB. Both patients died after a support time of 24 h because of multiorgan failure or neurological disorders after longer periods of resuscitation in the referral hospital. The third patient (55 years) received the Biomedicus pump as CVAD. Myocardial function recovered after a support time of 120 h, and the patient could be weaned. Unfortunately, 2 days after weaning, he developed malignant arrhythmias and died. The 2 remaining patients (15 years and 27 years) with diagnosis of acute fulminant virus myocarditis were supported by biventricular assist device (1 x Thoratec/lll days, 1 X Abiomed/7 days). During the entire time of support, there were no signs of myocardial recovery. The patients were accepted for the heart transplantation (HTX) program. In both cases, HTXs were performed without any complication. The postoperative course was uneventful. The results of mechanical circulatory support in patients with acute fulminant myocarditis are encouraging and justify the resources.
Development and Initial Testing of a Permanently Implantable Centrifugal Pump
Authors: Nakazawa Tadashi , Takami Yoshiyuki , Benkowski Robert , Ohtsubo Satoshi , Yukio Ohashi , Tayama Eiki , Ohtsuka Goro , Niimi Yoshinari , Glueck Julie , Sueoka Akinori , Schmallegger Helmut , Schima Heinrich , Wolner Ernst , Nosé Yukihiko
Published: November 2008

Abstract: To be able to salvage heart failure patients, the need for an economical permanent ventricular assist device is increasing. To meet this increasing demand, a miniaturized centrifugal blood pump has been developed as a permanently implantable device. The Gyro permanently implantable model (PI‐601) incorporates a sealless design with a blood stagnation free structure. The pump impeller is magnetically coupled to the driver magnet in a sealless manner. This pump is atraumatic and antithrombogenic and incorporates a double pivot bearing system. A miniaturized actuator was utilized in this system in collaboration with the University of Vienna. The priming volume of this pump is 20 ml. The overall size of the pump actuator package is 53 mm in height and 65 mm in diameter, 145 ml of displacement volume, and 305 g in weight. Testing to date has included in vitro hydraulic performance and hemolysis. This pump can provide 5 L/min against a 110 mm Hg total pressure head at 2,000 rpm and 8 Limin against 150 mm Hg at 2,500 rpm. The normalized index of hemo‐lysis (NIH) value of this pump was 0.0028 g/100 L at 5 Limin against 100 mm Hg. A preliminary anatomical study revealed the possibility of the implantability of 2 such systems in biventricular bypass at a preperitoneal location. This system is feasible for use as a permanently implantable biventricular assist device.
New Mechanism to Reduce the Size of the Monopivot Magnetic Suspension Blood Pump: Direct Drive Mechanism
Authors: Yamane Takashi , Nishida Masahiro , Kijima Toshihiko , Maekawa Jun
Published: November 2008

Abstract: Size reduction of the monopivot magnetic suspension blood pump has been achieved by reducing the size of the magnetic suspension and employing a direct drive mechanism in place of a brushless DC motor and a magnetic coupling. The flow has also been improved using a closed hollow impeller to remove flow obstruction at the inlet and using radial straight vanes to reduce the impeller speed by 30%. Hemolysis testing was conducted for the new models. Results showed that model DD1 presented only a slightly higher level of hemolysis than a regular extracorporeal centrifugal pump.
Renal Circulation and Cellular Metabolism During Left Ventricular Assisted Circulation: Comparison Study of Pulsatile and Nonpulsatile Assists
Authors: Sezai Akira , Shiono Motomi , Orime Yukihiko , Nakata Kini‐chi , Hata Mitsumasa , Yamada Hideaki , Iida Mitsuru , Kashiwazaki Satoshi , Kinishita Jun‐ichi , Nemoto Mitsuhiro , Koujima Takashi , Sezai Yukiyasu , Saitoh Toshimi
Published: November 2008

Abstract: We examined left ventricular assist during 6 h for an acute myocardial infarction model in pigs. The outflow cannula was placed in the ascending aorta and an inflow cannula in the left atrium. A pump (Pulsatile group: Zeon Medical and Nonpulsatile group: Nikkiso HPM‐15) was connected to each cannula. Items measured were the regional blood flow of the cortex and the medulla in the kidney, renal arterial flow, arterial blood ketone body ratio (AKBR), lactate/pyruvic acid, BUN, creatinine and β2‐microglobulin. After experimental study, the kidneys were removed, and a pathological study was performed. In the pulsatile assisted group, renal cortical blood flow increased but medulla blood flow decreased. On the other hand, in the nonpulsatile assisted group, both regional blood flows decreased. That means that in the pulsatile assisted group intrarenal redistribution improved, rather than in the nonpulsatile assisted group. The results of our study indicated that pulsatile assist produced superior circulation in the kidney, and the microcirculation on the cell level was superior as well in early treatment of acute left heart failure.
Study of Regional Cerebral Oxygen Saturation During Percutaneous Cardiopulmonary Support
Authors: Ninomiya Junichi , Hosaka Hiroki , Okada Daisuke , Fujii Masahiro , Saji Yoshiaki , Hinokiyama Kazuhiro , Satoh Yasuo , Nejima Jun , Takayama Morimasa , Takano Teruo , Tanaka Shigeo
Published: November 2008

Abstract: The purpose of this study was to evaluate the change of regional cerebral oxygen saturation (rSo2) during percutaneous cardiopulmonary support (PCPS) in patients with cardiogenic shock. Fifteen patients with cardiogenic shock were evaluated during PCPS by continuous monitoring of rSo2, systemic venous oxygen saturation (Svo2), and hemodynamics. The brain damage of these patients was also evaluated during and after PCPS. There were 10 males and 5 females. Their ages ranged from 57 to 79 years old (average: 60.0 ± 14). Two patients were unconscious before PCPS, and 11 received intraaortic balloon pumping (IABP) before PCPS. The change of rSo2was significantly correlated with the change of Svo,. The average of rSo2was 64 ± 3% at the stable hernodynamic condition. The rSo2with pulsatile PCPS was higher than that with nonpulsatile PCPS. There was no correlation between brain damage and rSo2. The patients with low rSo2(40%) that resulted in poor LV function could not be weaned from PCPS. In conclusion, the continuous monitoring of rSo2during PCPS could be a useful tool.
ADAMTS13 binds to CD36: a potential mechanism for platelet and endothelial localization of ADAMTS13
Authors: Davis Amanda K. , Makar Robert S. , Stowell Christopher P. , Kuter David J. , Dzik Walter H.
Published: November 2008

BACKGROUND: ADAMTS13 cleaves ultralarge von Willebrand factor (VWF) and plays a significant role in vascular biology and thrombotic thrombocytopenic purpura. CD36, a transmembrane protein present on endothelial cells and platelets (PLTs), binds to thrombospondin via three thrombospondin type 1 repeats. ADAMTS13 contains eight thrombospondin type 1 repeats.

STUDY DESIGN AND METHODS: An enzyme‐linked immunoassay was used to explore the binding of recombinant human CD36 (rHuCD36) to recombinant human ADAMTS13 (rHuADAMTS13). A competition assay between rHuADAMTS13 and recombinant human (rHu)‐thrombospondin‐2 for binding to CD36 was then performed. Subsequently, binding of rHuADAMTS13 to PLT membrane fragments expressing CD36 (PLT glycoprotein IV) and glycoprotein Ib/IX was assessed. To examine the functional significance of an ADAMTS13‐CD36 interaction, ADAMTS13 activity measured by a fluorescence resonance energy transfer assay was investigated in the presence of either rHuCD36 or concentrated PLTs.

RESULTS: rHuCD36 bound to rHuADAMTS13 in a dose‐dependent fashion. rHu‐thrombospondin‐2 competed with ADAMTS13 for CD36 occupancy, but even high concentrations of rHu‐thrombospondin‐2 failed to completely block binding of rHuADAMTS13 to rHuCD36. rHuADAMTS13 bound to PLT membrane fragments expressing CD36 (PLT glycoprotein IV) in preference to PLT membrane fragments expressing glycoprotein Ib/IX. ADAMTS13 activity was not inhibited by the presence of either rHuCD36 or concentrated PLTs.

CONCLUSION: rHuADAMTS13 binds to both rHuCD36 and PLT membrane CD36 in vitro. The binding of CD36 to rHuADAMTS13 with retention of its enzymatic activity is consistent with a proposed role for CD36 in localizing ADAMTS13 on the endothelial cell surface where it regulates the cleavage of VWF.
Mobilization kinetics of CD133+ hematoprogenitor cells for hematopoietic grafting
Authors: Jaime‐Pérez José C. , Hernández‐Alcántara Arely E. , Méndez‐Ramírez Nereida , Vázquez‐Garza Eduardo , Cantú‐Rodríguez Olga G. , Gómez‐Almaguer David
Published: November 2008

BACKGROUND: Quantification of CD34+ mononuclear cells is the most important quality control measure for hematopoietic stem cell (HSC) transplantation. A fraction of CD34+ cells also express the CD133 antigen. These cells constitute a group of earlier, less‐differentiated HSCs with a potentially higher capacity for engraftment. The correlation between total CD34+ peripheral HSCs and the fraction of these cells that coexpress CD133 was determined before and after automated collection by leukapheresis, as well as the effect of HSC CD133+ dose on hematopoiesis recovery.

STUDY DESIGN AND METHODS: Granulocyte–colony‐stimulating factor mobilization of HSCs from the marrow to the peripheral blood (PB) of allogeneic and autologous donors was followed by automated collection through leukapheresis on the fifth day. Quantification of CD34+ and CD133+ cells was performed on PB before collection and in the hematopoietic graft (HG) by flow cytometry.

RESULTS: There was a significant correlation between CD133+ and CD34+ HSCs in the PB before collection and in the final product for grafting (r = 0.62 and 0.64; p < 0.01). CD34+ HSCs per µL in PB and the HG was the only variable that did not correlate (r = 0.18). CD34+/CD133+ correlation increased from 0.33 on PB to 0.94 on the leukapheresis product (p < 0.01). Time to recovery was not related to CD133+ HSCs infused.

CONCLUSION: There was a significant correlation of both number per µL and percentage of CD34+/CD133+ HSCs before and after collection for transplantation; number of CD133+ cells had no apparent clinical impact on time to hematopoiesis regeneration.
STR Profiles from DNA Samples with “Undetected” or Low Quantifiler™ Results
Authors: Cupples Catherine M. , Champagne Jarrod R. , Lewis Kristen E. , Cruz Tracey Dawson
Published: November 2008

Abstract:  Screening methods capable of identifying DNA samples that will not yield short tandem repeat (STR) profiles are desired. In the past, quantitation methods have not been sensitive enough for this purpose. In this study, low level DNA samples were used to assess whether Quantifiler™ has a minimum quantitation value below which STR profiles would consistently fail to be detected. Buccal swabs were obtained and the DNA extracted, quantified, and serially diluted to concentrations ranging from 0.002 to 0.250 ng/μL. Samples were analyzed once with Quantifiler™, followed by Profiler Plus™ amplification and capillary electrophoresis analysis. An absolute minimum value below which STR results were unobtainable could not be defined. From the 96 low level samples tested, STR loci (including one full profile) were successfully amplified and detected from 27% of the samples “undetected” by Quantifiler™. However, no STR alleles were detected in 73% of these “undetected” samples, indicating that Quantifiler™ data may be useful for predicting STR typing success.