bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal Osteodystrophy in Dialysis Patients: Diagnosis and Treatment
Authors: Fournier Albert , Oprisiu Roxana , Hottelart Carine , Yverneau Paule Hardy , Ghazali Abderahmane , Atik Ahcène , Hedri Hafed , Said Said , Sechet Anne , Rasolombololona Mireille , Abighanem Oussama , Sarraj Ayman , Esper Najeh El , Moriniere Philippe , Boudailliez Bernard , Westeel Pierre‐François , Achard Jean‐Michel , Pruna André
Published: March 2003

Abstract: This article reviews the clinical, biological, radiological, and pathological procedures and their respective indications for the practical diagnosis of the following various histological patterns of renal osteodystrophy: osteitis fibrosa due to parathyroid hormone (PTH) hypersecretion; osteomalacia or rickets due to native vitamin D deficiency and/or aluminum overload; and adynamic bone disease (ABD) due to aluminum overload and/or PTH secretion oversuppression. Our advice regarding bone biopsy is to restrict it to patients with symptoms and hypercalcemia, especially those who have been previously exposed to aluminum. In other cases, we propose relying merely on the determination of the plasma concentrations of calcium, protide, phosphate, bicarbonate, intact PTH, aluminum, 25(OH)D3, and alkaline phosphatase (total and bony if hepatic disease is associated) to choose the appropriate treatment. Because of the danger of the desferrioxamine treatment necessary to chelate and remove aluminum, the suspicion of aluminic bone disease (osteomalacia or ABD) will always be confirmed by a bone biopsy. In the case of nonaluminic osteomalacia, correction of the vitamin D deficiency by native vitamin D or 25(OH)D3, and of the calcium deficiency and acidosis by alkaline salts of calcium and if necessary sodium bicarbonate are sufficient to cure the disease. In the case of nonaluminic ABD, the stimulation of PTH secretion by the discontinuation of 1α hydroxylated vitamin D and the induction of a negative calcium balance during dialysis by decreasing the calcium concentration in the dialysate will allow an increase of the CaCO3 dose to correct for hyperphosphatemia without inducing hypercalcemia. For hyperparathyroidism, i.e., plasma intact PTH levels greater than two‐ or four‐fold the upper limit of normal levels (according to the absence or presence of previous aluminum exposure), the treatment will consist in increasing the CaCO3 dose to correct for hyperphosphatemia together with a decrease of the calcium concentration in the dialysate if the dose of CaCO3 is so high that it induces hypercalcemia. When the hyperphosphatemia has been corrected and there is still a low or normal corrected plasma calcium level, 1α(OH)D3 in an oral bolus 2 or 3 times a week should be given at the minimal dose of 1 μg. When the PTH level stays above 400 pg while hypercalcemia occurs and hyperphosphatemia persists, surgical subtotal parathyroidectomy is recommended or the injection of calcitriol into the big nodular hyperplastic parathyroid glands under sonography control in high surgical risk patients. Special recommendations are given for children.
Hyperbaric Oxygenation, Plasma Exchange, and Hemodialysis for Treatment of Acute Liver Failure in a 3‐Year‐Old Child
Authors: Ponikvar  , Buturović  , Čižman  , Mekjavić  , Kandus  , Premru  , Urbančič  , Zakotnik  , Bren  , Ivanovich
Published: March 2003

A girl aged 3 years and 4 months weighing 16 kg was treated with plasma exchange (PE), hemodialysis (HD), and hyperbaric oxygenation (HBO) for acute hepatic failure and coma. She was given a total of 13 PEs, 13 HD sessions, and 9 HBO treatments over a period of 1 month. The initial 4 PEs were followed by HD sessions while the other 8 PE treatments were given simultaneously with HD. There was no renal failure; HD was instituted to improve ammonia elimination. In 1 HD session, 20% human albumin (370 ml) was used as the dialysate to enhance bilirubin elimination. Three volumes of plasma (2,000 ml) per PE were exchanged and replaced with fresh frozen plasma (FFP). The Bellco BL 791 plasmapheresis monitor and Gambro PF1000 and PF2000 plasma filters were used. Heparin was added to prevent clotting. A dual lumen pediatric HD catheter (7 Fr) placed percutaneously into the femoral vein was used as a blood access. The Fresenius 2008 C HD monitor and the Filtral 10 dialyzer were used for HD. PE and HD were instituted simultaneously to prevent the tetanic (hypocalcemic) cramps observed with 2 previous PEs due to citrate in the FFP. The extracorporeal circuit was primed with a mixture of concentrated red cells, human albumin, and saline solution and was discarded at the end of the procedure. The average blood flow rate in PE and/or HD circuits was 80 ml/min. During HBO, the girl breathed 100% oxygen at 2.5 atm for 90 min. Throughout the treatment, the patient was in good clinical, physical, and mental condition, but she was dependent on blood purification procedures. She was referred to a liver transplant center and successfully transplanted. The etiology of liver failure has not been clarified.
Filling Hemodialysis Catheters in the Interdialytic Period: Heparin Versus Citrate Versus Polygeline: A Prospective Randomized Study
Authors: Buturović Jadranka , Ponikvar Rafael , Kandus Aljoša , Boh Marko , Klinkmann Jens , Ivanovich Peter
Published: March 2003

Heparin and saline are commonly used to fill hemodialysis central venous catheters to prevent their thrombosis during the interdialytic period. The purpose of this prospective clinical study was to evaluate whether replacing heparin with citrate or polygeline could ensure satisfactory catheter function without exposing patients to the risk of systemic heparinization. Thirty end‐stage renal disease (ESRD) patients with subclavian or jugular single lumen catheters as temporary vascular access for hemodialysis were enrolled. After the insertion of the catheters, the patients were randomly assigned to one of the following three filling groups: Group A, heparin; Group B, citrate; Group C, polygeline. Before each dialysis, the filling solution was aspirated and clot volume, if present, was measured. The catheter usage time and the clot volume were 23 ± 24 days and 0.052 ± 0.035 ml in Group A, 51 ± 36 days and 0.059 ± 0.032 ml in Group B, and 32 ± 10 days and 0.056 ± 0.038 ml in Group C, respectively. Our results indicate that citrate or polygeline can replace heparin effectively as a filling solution for single lumen temporary hemodialysis catheters.
The Effect of Electrolyzed Strong Acid Aqueous Solution on Hemodialysis Equipment
Authors: Tanaka Noriaki , Fujisawa Tatsuya , Daimon Toshiya , Fujiwara Kouichi , Tanaka Noriko , Yamamoto Masanori , Abe Tomiya
Published: March 2003

Abstract: We reported the high effectiveness of electrolyzed strong acid aqueous solution (ESAAS) in cleaning hemodialysis lines. Although ESAAS has a strong bactericidal action, one concern is its strong acidity. It has a pH of 2.3–2.7, more than 1,000 mV in oxidation‐reduction potential (ORP), and 10–50 ppm of available chlorine. The possibility of metal corrosion, degradation of synthetic resins, chorine gas emission, or dissolving calcium carbonate (CaCO3) deposits due to ESAAS's acidity was tested using in vitro experiments. The bactericidal and antiviral effects of various ESAAS's were also tested. Metal corrosion and synthetic resin degradation, although they occurred, were not serious. There were no problems with chlorine gas emission and dissolving of CaCO3 deposits. Each type of ESAAS showed almost the same bactericidal and antiviral effect, but in some cases differences were observed.
Biocompatible Magnetic Polymer Carriers for In Vivo Radionuclide Delivery
Authors: Schütt Wolfgang , Grüttner Cordula , Teller Joachim , Westphal Fritz , Häfeli Urs , Paulke Bernd , Goetz Phil , Finck Wilhelm
Published: March 2003

The magnetic guidance of antiplastic and antibacterial agents as well as x‐ray and MRI contrast substances in vivo by means of magnetic particles has been attempted repeatedly during the last 2 decades with more or less success. When using microparticles, the circulation time in the blood, the biodistribution, and to a greater or lesser extent, the specific targeting are determined by the uniformity of size, chemical composition, surface modification, and the electric surface charge. The electrophoretic mobility is an important parameter for the prediction of the usefulness of the prepared particle, modified by chemical and biological molecules. For its success, radionuclide therapy depends on the critical relationship between the amount of radioactive isotopes in the target tissue and in critical normal tissue. Because the implementation of radioimmunotherapy for the treatment of cancer has proven to be considerably more difficult than initially anticipated, we propose the use of magnetic nanospheres for the well directed delivery of radionuclides to a tumor after the intravenous administration of the biodegradable colloidal suspension.
Present Status of the Total Artificial Heart at the University of Tokyo
Authors: Abe Yusuke , Chinzei Tsuneo , Isoyama Takashi , Ono Toshiya , Mochizuki Shuichi , Saito Itsuro , Guba Peter , Karita Tatsuro , Sun Yan Pin , Kouno Akimasa , Suzuki Takafumi , Baba Kazunori , Mabuchi Kunihiko , Imachi Kou
Published: March 2003

At the University of Tokyo, various types of total artificial heart (TAH) systems have been studied since 1959. At the present time, 2 types of implantable TAH have been developed. One is an undulation pump TAH (UPTAH) and the other is a flow transformed pulsatile TAH (FTPTAH). Using the UPTAH, 14 cases of implantation were performed in goats and 10 days' survival obtained. The new type of FTPTAH is under a prototype study. To prevent ring thrombus, a polyurethane membrane valve, a jellyfish valve, has been developed. The longest in vivo experiences with this valve in the TAH blood pump have been 312 days in the left side blood pump and 414 days in the right side blood pump. Conductance and arterial pressure based control (1/R control) can realize the physiological control of the TAH. Using 1/R control, 532 days of survival could be obtained in a goat with a paracorporeal TAH. The technique required to apply this control method to a implantable TAH is under development. We have proposed a new 5 year research project of the implantable TAH entitled “Comprehensive Basic Research on the Development of a Japanese Original Implantable Total Artificial Heart” to The Ministry of Welfare.
Personal Computer Supported Eight Channel Surface Stimulator for Paraplegic Walking: First Results
Authors: Bijak Manfred , Hofer Christian , Lanmüller Hermann , Mayr Winfried , Sauermann Stefan , Unger Ewald , Kern Helmut
Published: March 2003

Today functional electrical stimulation (FES) is used among other treatments to restore hand and arm function, to restore mobility of the lower extremities, for phrenic pacing, and in cardiomyoplasty. Common to all FES applications is that they require careful setup of stimulation parameters. To improve these tasks, personal computer (PC) based software for stimulation parameter evaluation and data acquisition was written. First, the described software was used to mobilize paraplegic patients in conjunction with an I2C bus controlled 8 channel surface stimulator. Electrodes were placed on each leg on the m. quadriceps and m. gluteus for hip and knee extension and the peroneal nerve to elicit flexion reflex. The fourth channel was used to correspond to subjects' individual needs. The stimulation patterns for standing up, walking, and sitting down easily could be set up and optimized by adjusting up to 128 stimulation parameters in a task‐specific way.
Experimental Study on Hemolysis in Centrifugal Blood Pumps: Improvement of Flow Visualization Method
Authors: Ahmed Shahriar , Funakubo Akio , Sakuma Ichiro , Fukui Yasuhiro , Dohi Takeyoshi
Published: March 2003

To evaluate rotary blood pumps, flow visualization is commonly applied to determine the flow patterns in a centrifugal blood pump, which have a relationship to its hemolytic performance. However, it is very troublesome to visualize the flow near the vanes due to the high rotational speed of the impeller. The rotational speed of the impeller in a centrifugal blood pump is usually several hundred revolutions per minute. In this study, we combined a high‐speed video camera based imaging method and an optical system in which the image of the rotating impeller was kept stationary. In the optical system, a prism rotating at half the speed of the impeller reflected the image of the impeller. The resultant reflected image was observed by a high‐speed video camera through a half mirror. With this optical setup, the image through the half mirror became stationary, and the path of a specific tracer particle could be traced for a longer duration. A longer duration of measurements and better quality of the obtained images were realized through this improvement. Movement of a specific tracer from the inlet portion to the outlet portion of the impeller could be examined using the developed method.
The Effects of Pulsatile Versus Nonpulsatile Perfusion on Blood Viscoelasticity Before and After Deep Hypothermic Circulatory Arrest in a Neonatal Piglet Model
Authors: Ündar Akif , Henderson Nancy , Thurston George B. , Masai Takafumi , Beyer Erik A. , Frazier  , Fraser Jr. Charles D.
Published: March 2003

Blood trauma increases blood viscoelasticity by increasing red cell aggregation and plasma viscosity and by decreasing cell deformability. During extracorporeal circulation, the mode of perfusion (pulsatile or nonpulsatile) may have a significant impact on blood trauma. In this study, a hydraulically driven dual chamber pulsatile pump system was compared to a standard nonpulsatile roller pump in terms of changes in the blood viscosity and elasticity during cardiopulmonary bypass (CPB) and pre and post deep hypothermic circulatory arrest (DHCA). Piglets, with an average weight of 3 kg, were used in the pulsatile (n = 5) or nonpulsatile group (n = 5). All animals were subjected to 25 min of hypothermia, 60 min of DHCA, 10 min of cold reperfusion, and 40 min of rewarming with a pump flow of 150 ml/kg/min. A pump rate of 150 bpm, pump ejection time of 120 ms, and stroke volume of 1 ml/kg were used during pulsatile CPB. Arterial blood samples were taken pre‐CPB (36°C), during normothermic CPB (35°C), during hypothermic CPB (25°C), pre‐DHCA (18°C), post‐DHCA (19°C), post‐rewarming (35°C), and post‐CPB (36°C). Viscosity and elasticity were measured at 2 Hz and 22°C and at strains of 0.2, 1, and 5 using the Vilastic‐3 Viscoelasticity Analyzer. Results suggest that the dual chamber neonate‐infant pulsatile pump system produces less blood trauma than the standard nonpulsatile roller pump as indicated by lower values of both viscosity and elasticity during CPB support.
Diminished Vasoconstrictive Function Caused by Long‐Term Nonpulsatile Left Heart Bypass
Authors: Nishimura Takashi , Tatsumi Eisuke , Nishinaka Tomohiro , Taenaka Yoshiyuki , Masuzawa Toru , Nakata Masako , Takano Hisateru
Published: March 2003

We investigated the functional changes of the systemic vascular system due to prolonged nonpulsatile left heart bypass (NPLHB). Three adult goats underwent pulsatile left heart bypass (PLHB). Two weeks later the PLHB was changed to the NPLHB, which was conducted for 4 weeks. The aortic pulse pressure was 39 and 16 mm Hg during the PLHB and NPLHB, respectively. Systemic vascular resistance (SVR) and the plasma norepinephrine level were measured at the end of PLHB (PUL), and in the 1st, 2nd, 3rd, and 4th weeks of NPLHB (NP1w, NP2w, NP3w, and NP4w). At each point, 1 μg/kg norepinephrine was injected, and the elevation of the SVR (ΔSVR) was calculated. The SVR and the plasma norepinephrine level did not change significantly during the entire course. However, ΔSVR decreased during NPLHB and became significantly lower at NP3w and NP4w than that at PUL (NP3w: 839 ± 164, NP4w: 746 ± 268, and PUL: 1,239 ± 324 dyne · s · cm−5). These results strongly indicated that prolonged NPLHB significantly diminished the constrictive function of the vascular system.
Coagulation and Anticoagulation in Extracorporeal Membrane Oxygenation
Authors: Muntean W.
Published: March 2003

Abstract: The hemostatic system poses a major problem in extracorporeal membrane oxygenation (ECMO). The foreign surface in the extracorporeal circuit activates platelets and the clotting system. To avoid loss of platelets and activation of the clotting system, anticoagulation is necessary. In addition, in many patients on ECMO, preexisting clotting disorders are present. Therefore, bleeding and/or thrombosis are frequent complications in ECMO patients that require specific treatment and may even necessitate termination of ECMO. Most ECMO centers use heparin for anticoagulation and the activated clotting time (ACT) for monitoring. Reduction of problems with hemostatis may be obtained with less thrombogenic surfaces, new anticoagulants with a short half‐life, platelet inhibitors, protease inhibitors, or selective anticoagulation in the extracorporeal circuit. While there will probably never be a complete nonthrombogenic surface available and all anticoagulants will have some risk of bleeding, improvement can be obtained by a combination of measures including better surfaces, more sophisticated anticoagulation regimens, and close laboratory monitoring.
Excessive Bleeding on Extracorporeal Membrane Oxygenation After Surgical Repair of Type I Truncus Arteriosus: A Case Report
Authors: Berger Angelika , Wollenek Gregor , Hermon Michael , Burda Gudrun
Published: March 2003

Abstract: Severe bleeding remains the most common complication of extracorporeal membrane oxygenation (ECMO) following surgical repair of congenital heart defects. We present a case of excessive hemorrhage within the first hours on ECMO support after repair of a type I truncus arteriosus. Bleeding control was achieved by surgical repair following failure of conventional interventions to control hemorrhage despite normalization of laboratory coagulation parameters. Aspects associated with bleeding and bleeding control during extracorporeal circulation after cardiac surgery are discussed.
Biodesign of a Skeletal Muscle Flap as a Model for Cardiac Assistance
Authors: Nikolaychik Victor V. , Chekanov Valeri S. , Hernandez Irene , Silverman Matthew D. , Lelkes Peter I.
Published: March 2003

Abstract: In using autologous muscles for cardiac assistance, it is crucial to reduce ischemia‐reperfusion injury in the surgically traumatized skeletal muscle. In adult sheep, we developed a simple model of surgically designed 2 latissimus dorsi muscle leaflets by modifying the vascular supply to these leaflets. Three pockets with graded injury were established, and muscle morphology and vascular remodeling were monitored in 3 experimental groups: muscle leaflets without any treatment (Group 1, n = 6) that served as controls; muscle leaflets integrated with a fibrin interlayer (Group 2, n = 6); and leaflets integrated with fibrin and entrapped pyrrolostatin (Group 3, n = 6). We applied the fibrinogen and thrombin solutions, which polymerize to form a three‐dimensional meshwork joining the tissues, creating a provisional matrix for angiogenesis, and acting as a delivery depot for agents aimed at minimizing ischemia‐reperfusion lesion formation. After 2 months, the muscle leaflets biointegrated with the fibrin interface showed none of the signs of necrosis or ischemia‐reperfusion lesions seen in the controls. Although no angiogenic factors were incorporated, the fibrin interlayer rapidly (<2 weeks) became a densely vascularized tissue replete with a voluminous capillary network. In contrast, controls showed poor bonding between the tissues, muscle fiber deterioration, and a compromised vascular network. Muscle structure was best preserved and angiogenesis was greatest when pyrrolostatin, a free radical scavenger, was added to the fibrin meshwork to reduce damage caused by overproduction of free radicals. This newly designed model will be useful to study many current approaches in cardiovascular biology, from pharmaceuticals to gene therapy, which might prove advantageous in muscle‐designed cardiac assistance.
Modeling Flow Effects on Thrombotic Deposition in a Membrane Oxygenator
Authors: Gartner Mark J. , Wilhelm Carl R. , Gage Kenneth L. , Fabrizio M. Charlene , Wagner William R.
Published: March 2003

Abstract: The hypothesis that regions of low blood velocity in a membrane oxygenator, as predicted by computational fluid dynamics (CFD), would correspond with regions of clinical thrombotic deposition was investigated. Twenty heparin‐coated oxygenators were sectioned following use in adult extracorporeal membrane oxygenation. The activated clotting time (ACT) was maintained at approximately 180 s via heparin infusion throughout the support period. Cross‐sections were systematically photographed, and slides made to allow image projection upon a digitizing pad. Thrombotic deposition was traced to allow creation of a device cross‐section image with an overlaid color scale representing thrombotic deposition frequency. A two‐dimensional CFD model was developed to predict blood velocities throughout the oxygenator cross‐section. Direct spatial comparisons were made between maps of CFD modeled blood speed and thrombotic deposition. Theoretical oxygenator design modification was performed within the CFD model to investigate flow paths which might minimize regions of low blood velocity. CFD results demonstrated that low velocity regions qualitatively matched regions with a high incidence of thrombotic deposition. Thrombotic deposition was also correlated to longer perfusion periods. This technique of coupling clinical data and CFD offers the potential to relate flow characteristics to thrombotic deposition and represents a potentially powerful new methodology for the optimization of oxygenator flow‐related biocompatibility.
Small Diameter Vascular Prosthesis with a Nonthrombogenic Phospholipid Polymer Surface: Preliminary Study of a New Concept for Functioning in the Absence of Pseudo‐ or Neointima Formation
Authors: Yoneyama Toshikazu , Ito Masashi , Sugihara Ken‐ichi , Ishihara Kazuhiko , Nakabayashi Nobuo
Published: March 2003

Abstract: The purpose of this study was to prepare a small diameter vascular prosthesis functioning without pseudointima formation. A nonthrombogenic phospholipid polymer, the 2‐methacryloyloxyethyl phosphorylcholine (MPC) polymer, has a cell membrane‐like structure and has demonstrated strong nonthrombogenicity. We have recently prepared 2 kinds of vascular prostheses, 2 mm in diameter, composed of the MPC polymer and segmented polyurethane (SPU). One includes 7.5 wt% MPC polymer (SPU/MPC[7.5] prosthesis), and the other includes 10.0 wt% (SPU/MPC[10] prosthesis). These prostheses were placed in rabbit carotid arteries and were retrieved at 1 and 4 weeks after implantation. A pseudointima was observed at 4 weeks on the SPU/MPC(7.5). For the SPU/MPC(10), the surface was macroscopically clear without a pseudointima even after a 4 week implantation. It appears that the SPU/MPC(10) prosthesis, functioning without a pseudointima, possesses a stronger nonthrombogenicity and would be more applicable for clinical use.
Modified Ultrafiltration Improves Carbon Dioxide Removal After Cardiopulmonary Bypass in Infants
Authors: Aeba Ryo , Katogi Toshiyuki , Omoto Tadashi , Kashima Ichiro , Kawada Shiaki
Published: March 2003

Abstract: Little is known about the role of modified ultrafiltration in ameliorating the adverse effects of the cardiopulmonary bypass on pulmonary function in infants. Twenty‐nine nonrandomized consecutive infants (<12 months of age) who underwent unrestrictive ventricular septal defect closure between 1995 and 1998 were included in this study. Down's syndrome was associated in 9 patients. The actual ventilator settings were highly homogeneous among all patients and each time point in the study. Fourteen infants received modified ultrafiltration after the discontinuation of cardiopulmonary bypass. Fifteen untreated patients served as the control group. Correlates of cardiac and pulmonary functions for both groups were compared. The arterial carbon dioxide tension in the experimental group was significantly lower than in the control group from 20 to 240 min after bypass. Arterial oxygenation and pulmonary arterial pressure were similar in the 2 groups. Modified ultrafiltration improves carbon dioxide removal after cardiopulmonary bypass in infants. This may potentially convey a beneficial impact on hemodynamics.
Analysis of the Arterial Blood Pressure Waveform Using Fast Fourier Transform Technique During Left Ventricular Nonpulsatile Assistance: In Vitro Study
Authors: Kawahito Shinji , Nakata Kin‐ichi , Nonaka Kenji , Sato Tsutomu , Yoshikawa Masaharu , Takano Tamaki , Maeda Tomohiro , Linneweber Joerg , Schulte‐Eistrup Sebastian , Flowers Don , Glueck Julie , Nosé Yukihiko
Published: March 2003

Abstract: The arterial blood pressure waveform is variable during left ventricular assistance. The aim of this study is to examine the correlation between the left ventricular assist device (LVAD) condition and the arterial blood pressure waveform in a fixed cardiac output condition using a mock circuit. This mock circulation loop was composed of an aortic compliance chamber, a left atrial compliance chamber, a pneumatic pulsatile pump as a native heart, and a rotary blood pump representing the LVAD with left atrial drainage. The Fast Fourier Transform technique was utilized to analyze the arterial blood pressure waveform and calculate the pulsatility index (PI) and the pulse power index (PPI). The PI and PPI decreased with the increase of the LVAD rotational speed, exponentially. There was a significant negative correlation between the PI, PPI, and the LVAD rotational speed, flow rate, and assist ratio. The best correlation was observed between the PPI and the assist ratio (r = 0.986). From this viewpoint, an ideal LVAD condition may be estimated from the pulsatility change of the arterial blood pressure waveform.
Electronmicroscopic Changes in Selected Vital Organs After Long‐Term Total Artificial Heart Pumping in Animal Experiments
Authors: Vašků Jaromír , Dobšák Petr
Published: March 2003

Abstract:Electronmicroscopic (EM) evaluation of selected vital organs (liver, kidney, lung) informs us about otherwise hardly detectable changes during total artificial heart (TAH) pumping. In our experiments, we compared 2 groups of long‐surviving animals in which the TAH TNS‐BRNO pneumatic device was implanted (TNS‐BRNO‐II and VII in 45 experiments, TNS‐BRNO‐III in 1 experiment, and TNS‐BRNO‐VIII in 1 experiment). In 4 experiments, the Rostock TAH (NABEL, TAH Research Center, Rostock, Germany) was implanted. One group of 22 animals with an average survival of 162 days (the longest, 293 days) was submitted to an antihypertensive treatment; another 1 of 29 calves with an average survival of 98 days (the longest, 173 days) was untreated. The evaluation was performed using a scale (0 to 3) based on very precisely fixed criteria. EM pathologic changes documented various stages of ischemic damage. Except for the liver, no significant difference was found between both groups, despite the substantially prolonged survival in the treated group. Very important was the general state of mitochondria, endoplasmic reticulum, and nucleus. Further, the state of glomerular podocytes in the kidney and the state of interalveolar septa and of pneumocytes constituting the air‐blood barrier for gas exchange in the lungs are especially important. In some animals of both groups, the EM findings were completely normal, especially in the lung.
In Vitro Evaluation of Open Heart Surgery Tubing Coated with Heparin and Lipid
Authors: Novello Waldyr Parolari , Santana Maria Helena , Fonseca de Arruda Antonio Celso
Published: March 2003

Abstract: The aim of this work was to evaluate in vitro the tromboresistence, hemolysis tendency, platelet adhesion, cytotoxicity, physicochemical properties, and stability of open‐heart tubing coated with fractionated heparin‐benzalkonium chloride and/or lipid dipalmitoyl
l‐α‐phosphatidylcholine (DPPC). The tendency for clot formation and platelet adhesion was greater in noncoated and lipid‐coated tubing than in heparin‐coated tubing. There were no significant differences between the hemolytic potentials of coated and noncoated tubing. The coatings were stable during the time of the experiment. The coatings did not present cytotoxicity and physicochemical alterations.
Fluid Dynamics of a Pediatric Ventricular Assist Device
Authors: Bachmann Christopher , Hugo Geoff , Rosenberg Gerson , Deutsch Steve , Fontaine Arnold , Tarbell John M.
Published: March 2003

Abstract: The number of pediatric patients requiring some form of mechanical circulatory assistance is growing throughout the world because of new surgical procedures and the success of pediatric cardiac transplantation. However, the salvage rate for those patients requiring circulatory support may be as low as 25%. Despite the fact that Penn State's 70 cc pneumatic ventricular assist device has been used with a success rate of over 90% in more than 250 patients worldwide, efforts to scale down the pump have encountered difficulties. Animal experiments with a 15 cc version were unsuccessful, with explanted pumps showing extensive thrombus deposition within the pumping chamber. The materials used to fabricate the smaller pump as well as the basic operating principles are identical to the successful adult‐sized version. It is therefore believed that reducing the size of the pump altered the internal flow field, and that fluid dynamic factors were responsible for the high degree of thrombus observed with the implanted devices. A dimensional analysis was conducted that revealed significant differences in both Reynolds (Re) and Strouhal (St) numbers between the successful and unsuccessful pumps. Two component laser Doppler velocimetry was then used to characterize the internal flow field quantitatively. Comparison with data from the 70 cc pump showed a reduction in wall shear stress and turbulence levels in the 15 cc pump that would yield an environment conducive to clot formation.
Biostability, Inflammatory Response, and Healing Characteristics of a Fluoropassivated Polyester‐Knit Mesh in the Repair of Experimental Abdominal Hernias
Authors: Marois Yves , Cadi Rachida , Gourdon Jim , Fatouraee Nasser , King Martin W. , Zhang Ze , Guidoin Robert
Published: March 2003

Abstract: The present study was undertaken to validate the benefits of a fluoropolymer treatment on the biostability, inflammatory response, and healing characteristics of a polyester mesh used for hernia repair, the Fluoromesh, as compared to a commercial monofilament‐knit polypropylene mesh, Marlex, used as the control. Both were implanted for the repair of surgically induced abdominal hernias in piglets for prescheduled durations of implantation of 4, 15, and 60 days. The mesh and surrounding tissue were harvested at the sacrifice for the bursting strength and inflammatory response measurements in terms of alkaline and acid phosphatase secretion in the tissue, and for histological observations of the healing sequence and tissue thickness measurements by histomorphometric techniques. After cleaning to remove adherent tissue, the presence of the fluoropolymer at the surface of the mesh was detected using SEM and ESCA. The results demonstrated greater mechanical reinforcement and tissue development for the Fluoromesh than for the polypropylene mesh. The healing performance of the Fluoromesh was attributed to a more intense chronic inflammatory reaction early after implantation that stimulated significantly greater tissue ingrowth and integration. The concentration of fluoropolymer at the surface of the mesh was masked as a result of biological species adsorption. Textile analysis revealed that the Fluoromesh was dimensionally more stable in vivo than the polypropylene control mesh, which demonstrated stretching in the weft direction and shrinking in the warp direction during implantation.
Development of a Completely Closed Circuit Using an Air Filter in a Drainage Circuit for Minimally Invasive Cardiac Surgery
Authors: Matayoshi Toru , Yozu Ryohei , Morita Masanori , Shin Hankei , Mitsumaru Atsuhiro , Kawada Shiaki
Published: March 2003

Abstract: The completely closed circuit system is the future direction of cardiopulmonary bypass because of its compactness and superior biocompatibility. The most serious obstacle for clinical application is the sucking of air bubbles into the drainage circuit. The purpose of this study was to remove the air bubbles from the drainage circuit. Infusing 50 ml/min of air bubbles into the drainage circuit of the usual closed circuit, and infusing 50, 100, and 150 ml/min of air into the drainage circuit of a newly developed closed circuit (drainage circuit using an air filter), the number and size of air bubbles were observed at the outlet of the arterial filter. In the usual closed circuit, many air bubbles of over 40 μm were detected within 5 s at a blood flow of 4 L/min because the centrifugal pump decreased the size of the bubbles, which then passed through the oxygenator and arterial filter. Air bubbles of over 40 μ were not detected in the newly developed closed circuit within 5 min at a blood flow of 4 L/min. The removal of air mixed into the completely closed circuit was possible with a drainage circuit using an air filter that was developed. The clinical use of the completely closed circuit for minimally invasive cardiac surgery (MICS) became possible based on this development.
Particle Image Velocimetry Analysis of the Flow Field in the Total Cavopulmonary Connection
Authors: Grigioni M. , Amodeo A. , Daniele C. , D'avenio G. , Formigari R. , Di Donato R.M.
Published: March 2003

Abstract: The total cavopulmonary connection (TCPC) is a common operation, meant to restore a proper pulmonary blood flow in heart defects with only one functional ventricle. It consists of the direct connection of the venae cavae to the pulmonary arteries in a cross‐shaped disposition which entails a peculiar hemodynamics: Side effects can occur, such as recirculation zones and pressure drop across the connection. Our study is aimed at the quantitative investigation of the flow field of a successful Fontan‐type operation, in view of the clinical importance of assuring a nearly physiological pulmonary blood flow, especially if one considers that many pediatric patients are eligible for this operation. A glass‐blown TCPC phantom, realized according to nuclear magnetic resonance data, was employed in a steady‐flow loop. Thus, a realistic model of this Fontan‐type operation was realized using materials which enable advanced measurement techniques such as particle image velocimetry (PIV). The mean flow rates at each branch of the cavopulmonary shunt could be independently varied with a vertical shift of the corresponding upstream reservoir. The PIV technique was used successfully in identifying the flow field characteristics. The flow field in this TCPC topology was shown to be well organized and regulated by the presence of a vortex at the confluence of the venae cavae. The effect of different loading conditions, which realistically can be found in vivo, is studied with a high spatial resolution, showing the possibility to use pulmonary resistance as a parameter in designing the surgical geometry.
Analysis of the Arterial Blood Pressure Waveform During Left Ventricular Nonpulsatile Assistance in Animal Models
Authors: Kawahito Shinji , Takano Tamaki , Nakata Kin‐ichi , Maeda Tomohiro , Nonaka Kenji , Linneweber Joerg , Schulte‐Eistrup Sebastian , Sato Tsutomu , Mikami Minoru , Glueck Julie , Nosé Yukihiko
Published: March 2003

Abstract: When the rotary blood pump is used as a left ventricular assist device (LVAD), the arterial blood pressure waveform changes with the LVAD condition. Based on evidence from an in vitro study, the change of the arterial blood pressure waveform during left ventricular assistance was evaluated using animal models. After the left pleural cavity was opened through the fifth intercostal space under general anesthesia, a rotary blood pump was implanted as an LVAD into 6 healthy calves. The direct left carotid arterial blood pressure waveform was measured and recorded by an oscilloscope. The Fast Fourier Transform technique was utilized to analyze the arterial blood pressure waveform and calculate the pulsatility index (PI) and the pulse power index (PPI). Similar to the in vitro study, the PI and PPI decreased exponentially with the increase of the LVAD assist ratio. By using this analysis methodology, a physiologically effective ventricular assistance might be achieved.
DegraPol‐Foam: A Degradable and Highly Porous Polyesterurethane Foam as a New Substrate for Bone Formation
Authors: Saad B. , Kuboki Y. , Welti M. , Uhlschmid G.K. , Neuenschwander P. , Suter U.W.
Published: March 2003

Abstract: Bone morphogenetic protein (BMP) is known to require a suitable carrier to induce ectopic bone formation in vivo. To evaluate the suitability of DegraPol‐foam, a degradable, elastic, and highly porous polyesterurethane foam as carrier for BMP‐induced bone formation, a fraction containing all the active BMPs (BMP cocktail) was combined with DegraPol‐foam and implanted subcutaneously into rats. DegraPol‐BMP scaffolds were found to induce osteogenesis 2 weeks after implantation as evidenced by morphological and biochemical observations. In addition, the osteoblast‐compatibility of DegraPol‐foam was examined here. In vitro, primary rat osteoblasts and osteoblasts from the human cell line (HFO1) attached and proliferated preferentially on the surface of the DegraPol‐foam. Both cell types exhibited relatively high attachment and low doubling time that resulted in a confluent cell multilayer with spindle‐shaped morphology on the surface of the foam. Osteoblasts produced high concentrations of collagen type I and osteocalcin, and expressed increasing levels of alkaline phosphatase (ALP) activity. Taken collectively, both osteoblasts from rat tibia and from the human cell line HFO1 showed high cell attachment and growth, and preserved their phenotype. The geometrical structure of DegraPol is a suitable carrier for BMP for the induction of bone formation.
Effects of Ischemic Preconditioning and Synchronized Coronary Venous Retroperfusion in an Off‐Pump Coronary Artery Bypass Grafting Model
Authors: Hatori Nobuo , Segawa Daisuke , Hinokiyama Kazuhiro , Kimura Tamizo , Iizuka Yasuhiro , Ochi Masami , Tanaka Shigeo
Published: March 2003

Abstract: Off‐pump coronary artery bypass grafting (CABG) has become a popular procedure. However, temporary occlusion of the target vessel is sometimes a threat to the patients. Although ischemic preconditioning (IP) has been proposed to reduce myocardial injury, its effects remain controversial. The coronary veins represent an alternate route for delivery of therapeutic agents and arterial blood to the acutely ischemic myocardium. The aim of this study was to investigate the protective effect against myocardial ischemia and reperfusion injury of combined IP and synchronized coronary venous retroperfusion (SCVR) in an off‐pump CABG model. Twenty‐one pigs were assigned to 3 groups of 7 animals. In the control group, the left anterior descending coronary artery (LAD) was occluded for 45 min followed by 2 h of reperfusion using a left intrathoracic artery (LITA) bypass circuit. In the IP group, LAD occlusion was done for 5 min with 15 min of reperfusion, followed by 45 min of LAD occlusion. In the SCVR group, pretreatment before LAD occlusion was the same as in the IP group. Then, SCVR was commenced just after the start of LAD occlusion for 45 min. The percent systolic shortening of ischemic myocardium (measured by sonomicrometry) after reperfusion via the LITA was significantly (p < 0.001) greater in the SCVR group (14.6 ± 3.3%) than in the control group (−1.6 ± 5.6%, 95%CI: −24.3 –−8.1) or the IP group (0.7 ± 8.0%, 95%CI: −22.0 –−5.8) after 30 min of reperfusion, and this difference persisted throughout the reperfusion period. Infarct size (expressed as a percentage of the area at risk) was significantly (p < 0.001) smaller in the SCVR group (2.4 ± 2.7%) than in the control group (83.0 ± 2.3%, 95%CI: −99.0 –−62.4) or the IP group (42.0 ± 23.0%, 95%CI: −58.0 –−21.3). Combined SCVR and IP had a potent myocardial protective effect in the present off‐pump CABG model. This method may be clinically feasible and may be able to prolong a safe coronary occlusion.
Polymethylmethacrylate Efficacy in Reduction of Renal Itching in Hemodialysis Patients: Crossover Study and Role of Tumor Necrosis Factor‐α
Authors: Kato Akihiko , Takita Takako , Furuhashi Mitsuyoshi , Takahashi Toshiyuki , Watanabe Tetsuya , Maruyama Yukitaka , Hishida Akira
Published: March 2003

Abstract: Pruritus is one of the major unsolved problems for patients receiving regular hemodialysis. In this study, we conducted a 6 month prospective and crossover trial to investigate the effect of polymethylmethacrylate (PMMA) membrane for renal itching. We also examined the role of the tumor necrosis factor (TNF)‐α system for pruritus in hemodialysis patients. We assessed the degree of skin itching and measured circulating levels of TNF‐α and soluble TNF receptors (sTNFR‐I, sTNFR‐II) in 19 patients using hemodialysis, complicated by prolonged severe pruritus for 6 months. Serum sTNFR‐I and II levels were significantly elevated in hemodialysis patients compared to normal subjects. Serum sTNFR‐II levels were significantly and negatively correlated with serum albumin (r = −0.602, p = 0.007). A significant positive relationship was also found between sTNFR‐I and erythropoietin dosage (r = 0.554, p = 0.016). However, no association was found between the degree of pruritus and circulating sTNFR‐I and II values. Skin itching scale was significantly decreased from 2.7 ± 0.2 to 2.1 ± 0.3 following the use of PMMA membrane for 3 months (p < 0.05). In contrast, there was no change in itching scales during 3 months of conventional therapy (2.2 ± 0.3 versus 2.2 ± 0.3, p = NS). PMMA itself did not affect serum TNF‐α and sTNFR values as well as conventional dialyzer membranes. These findings suggested that the PMMA dialyzer can improve renal itching not mediated through the modification of the TNF‐α system.
Liver Stem Cells: A Potential Source of Hepatocytes for the Treatment of Human Liver Disease
Authors: Faris Ronald A. , Konkin Tamako , Halpert Gretchen
Published: March 2003

Abstract: Severe liver injury often leads to the proliferation of oval cells, which differentiate along hepatocytic and biliary lineages. Because oval cells proliferate only when hepatocyte replication is impaired, they are considered to be the progeny of facultative liver stem cells (FLSCs). Identification and isolation of FLSCs has been hampered by the lack of markers that delineate these bipotential progenitors. We hypothesized that transition ductal cells are FLSCs because they are located in a unique anatomical niche sharing tight junctions with a neighboring hepatocyte and another terminal ductular cell. Alternatively, it has been proposed recently that bone marrow‐derived stem cells are FLSCs since these cells differentiate along the hepatic lineage following colonization of the liver. The intent of this review is to provide insight into the nature and origin of liver stem cells and to explore the possibility that stem cell technology may lead to the development of clinical modalities for the treatment of human liver disease.
Novel Strategies for Immortalization of Human Hepatocytes
Authors: Cascio Stephanie M.
Published: March 2003

Abstract: Normal somatic cells have a finite life span due in part to their inability to maintain telomere length and chromosome stability. Immortalization strategies based on recent advances in telomere biology and aging research have led to the creation of genetically stable, nontumorigenic immortalized cell lines. Reversible immortalization, using the Cre‐lox recombination and excision system, has been developed for the expansion of primary cells for cell based clinical therapies. Immortalized human hepatocyte cell lines with differentiated liver functions would find broad applications in biomedical research, especially for pharmacology and toxicology, artificial liver support, and hepatocyte transplantation. The biological basis of these new immortalization methods and their application to human hepatocytes is reviewed.
Bioartificial Liver Treatment Prolongs Survival and Lowers Intracranial Pressure in Pigs with Fulminant Hepatic Failure
Authors: Khalili Theodore M. , Navarro Antonio , Ting Paul , Kamohara Yukio , Arkadopoulos Nikolaos , Solomon Barry A. , Demetriou Achilles A. , Rozga Jacek
Published: March 2003

Abstract: Intracranial hypertension leading to brainstem coning is a major cause of death in fulminant hepatic failure (FHF). We have developed a bioartificial liver (BAL) utilizing plasma perfusion through a bioreactor loaded with porcine hepatocytes and a column with activated charcoal. In a Phase I clinical trial, we observed a decrease in intracranial pressure (ICP) in FHF patients. However, these patients received BAL therapy together with other measures. We therefore examined whether BAL therapy alone could prevent development of intracranial hypertension in pigs with surgically induced FHF. Pigs (40–60 kg) underwent end‐to‐side portacaval shunt, transection of all hepatic ligaments, and placement of slings around the hepatic artery and bile duct. After 3 days, the slings were tightened to induce liver necrosis. After 4 h, Group 1 pigs (n = 6) underwent a 6 h treatment with the BAL utilizing 10 billion cryopreserved pig hepatocytes and a charcoal column, Group 2 pigs (n = 6) with the BAL containing charcoal but no cells, and Group 3 pigs (n = 6) with the BAL containing neither cells nor charcoal. Group 1 pigs maintained a normal ICP during BAL treatment and for 14 h afterward and because of this effect they survived longer than Groups 2 and 3 animals. In contrast, Groups 2 and 3 pigs showed an early (6–8 h) rise in ICP.