bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Intravenous and Subcutaneous Application of Recombinant Human Erythropoietin: A Multicenter Trial
Authors: Schaller R. , Sperschneider H. , Thieler H. , Dutz W. , Hans S. , Voigt D. , Marx M. , Engelmann J. , Schöter K. –H. , Scigalla P. , Stein G.
Published: November 2008

Abstract: The aims of this clinical study were to compare the maintenance doses for intravenous (IV) and subcutaneous (SC) administration of recombinant human erythropoietin (rhEPO) and to investigate whether there is any difference in the increase of the packed cellular volume (PCV) per week under IV and SC administration of rhEPO from two production sites (Genetics Institute, Cambridge, USA; and Boehringer Mannheim, Penzberg, Germany). A total of 90 patients suffering from end–stage renal disease were included in the study. All patients had already been treated for at least 6 months with chronic hemodialysis. The study was carried out as a randomized, multicenter parallel group comparison study with a 1–week pretreatment phase, a subsequent 8–week double–blind phase, and a final open phase. The final open phase consisted of a correction phase and a maintenance phase. The production site had no influence on the PCV increase per week, and there were no differences with respect to tolerability. The median rhEPO dose required to maintain the target PCV of 30 to 35 vol. % was 33 U/kg body weight three times a week in the IV group compared with 22 U/kg in the SC group (i. e., an average of 30% less with SC administration). Development or aggravation of hypertension under rhEPO therapy was observed, especially during the correction phase and more frequently in the SC group than in the IV group. During the maintenance phase, there was no essential difference between the two groups.
Life–Saving Effect of Pyridoxalated Hemoglobin–Polyoxyethylene Conjugate on Carbon Monoxide Intoxication of Rabbits
Authors: Uchiyama Toshimtsu , Harafuji Keizo
Published: November 2008

Abstract:We examined whether pyridoxalated hemoglo–bin–polyoxyethylene conjugate (PHP) could be life–relievable for carbon monoxide (CO) intoxication. Toxic gas (O2, 5. 0%; CO2, 16. 0%; CO, 1. 8%; and N2, 77. 2%) was inhaled by rabbits anesthetized with urethane and the following parameters were measured: blood pressure, arterial and venous PO2, PCO2, pH, and carboxyhemoglobin (COHb). When mean blood pressure reached 0 or 20 mm Hg as an index after inhalation of the toxic gas, the toxic gas was switched to air; intravenous infusion of physiological saline or PHP (1. 2 g/20 ml/kg/30 min) was simultaneously initiated. In the experiment using 0 mm Hg blood pressure, PHP prolonged the survival time and exhibited significant temporary recovery of PO2and PCO2in comparison with saline. In the experiment using the 20 mm Hg blood pressure, a significant difference in each parameter was observed between the saline and PHP groups. Two of 8 animals in the saline group died without any recovery of each parameter. All 6 animals in the PHP group survived and each parameter recovered. PHP accelerated recovery from high COHb concentrations, low arterial and venous PO2, reduction of arterial and venous PCO2, and elevations of pH and blood pressure. These results suggest that PHP treatment during the early stage of CO intoxication is life–saving and effective in facilitating the recovery of various functions.
In Vitro Evaluation of Platelet/Biomaterial Interactions in an Epifluorescent Video Microscopy Combined with a Parallel Plate Flow Cell
Authors: Kawagoishi Nobuchika , Nojiri Chisato , Senshu Kazuhisa , Kido Takayuki , Nagai Hirofumi , Kanamori Toshiyuki , Sakai Kiyotaka , Koyanagi Hitoshi , Akutsu Tetsuzo
Published: November 2008

Abstract: Suitable evaluation systems are critical for ranking various biomaterials in order to develop a method to design and synthesize nonthrombogenic biomaterials. We have recently developed an in vitro test system to evaluate platelet/biomaterial interactions in whole blood. The system consists of a parallel plate flow cell and epifluorescent video microscopy (EVM). A glass coverslip coated with a polymer was incorporated into the flow cell, and blood was perfused using a syringe pump via a polymer–coated PVC tubing connected to the flow cell. Whole human blood was anticoagulated with heparin (2 U/ml), and the platelets were labeled with the fluorescent dye mepacrine (5 μM). This system permitted real–time and dynamic observations of platelet/biomaterial interactions in whole blood under a defined flow condition. In order to evaluate the feasibility of this system, two different segmented polyether–polyurethanes (SPEUs), PU–PTMG(650) and PU–PTMG(2000), were chosen as test polymers. Surface characteristics verified with electron spectroscopy for chemical analysis (ESCA) and contact angle measurements showed similar results in both SPEUs. Blood was perfused at a wall shear rate of 200 s–1 for 20 min. Excitation light was applied for 2 s at 1 min intervals. The real–time image was then analyzed at each time point for the percentage of surface area of platelet coverage. Plasma β–thromboglobulin (β–TG) levels were also measured before and after each run. PU–PTMG(650) showed a significantly higher number of adhered platelets than PU–PTMG(2000) at each time point. β–TG levels of PU–PTMG(650) were also higher than those of PU–PTMG(2000), which is comparable to the results of EVM. Thus, this EVM system has been proven to be an excellent and highly sensitive in vitro analytical method for evaluating platelet/biomaterial interactions.
Culture of a Differentiated Liver Cell Line, Hep G2, in Serum with Application to a Bioartificial Liver: Effect of Supplementation of Serum with Amino Acids
Authors: Melkonian Amie D. , Gaylor John D. S. , Cousins Roderick B. , Grant M. Helen
Published: November 2008

Abstract: Much effort has been directed toward the development of serum–free, hormonally defined culture conditions for the maintenance of differentiated functions in many cell types, including hepatocytes. However, in the development of a hepatocyte bioreactor for artificial liver support, many designs propose the maintenance of cells in plasma as opposed to defined culture medium. There is very little reported literature on the growth and function of cells cultured in plasma or serum; therefore, the effect of increasing serum concentrations was investigated using the human hepatoma, Hep G2, as a model cell line. It was found that Hep G2 can survive and grow in 100% serum if the serum is supplemented with L–glutamic acid, glycine, and L–cysteine.
Chaotic Hemodynamics During Oscillated Blood Flow
Authors: Yambe Tomoyuki , Nitta Shin–ichi , Sonobe Taro , Naganuma Shigeru , Kakinuma Yoshito , Kobayashi Shin–ichi , Tanaka Motonao , Fukuju Takeo , Miura Makoto , Sato Naoshi , Mohri Hitoshi , Koide Satoshi , Takeda Hiroshi , Yoshizawa Makoto , Kasai Takeshi , Hashimoto Hiroyuki
Published: November 2008

Abstract: A vibrating flow pump (VFP), which can generate oscillated blood flow (10–50 Hz/min), has been developed by our team for the artificial heart system. However, the flow pattern of this pump was different from that of the natural heart; therefore, it is important to analyze the effect of this oscillated blood flow on the circulatory regulatory system. To analyze the hemodynamics of high frequency oscillated blood flow as an entity, (not decomposed), nonlinear mathematical techniques were utilized. VFPs were implanted between the left atrium in animal experiments using adult goats. After the implantation procedure, the ascending aorta was clamped to constitute the complete left heart circulation with VFP. Using a nonlinear mathematical technique, an arterial blood pressure waveform was embedded into four–dimensional phase space and projected into three–dimensional phase space. The Lyapunov numerical method was used as an adjunct to graphic analysis of the state space. Phase portrait of the attractor showed a high dimension complex structure, suggesting deterministic chaos during natural circulation. However, phase portrait of the hemodynamics during oscillated blood flow showed a single circle with banding and a forbidden zone, similar to a limit–cycle attractor, suggesting a lower dimensional dynamic system. Positive Lyapunov exponent during oscillated blood flow suggests the existence of lower dimensional chaotic dynamics. These results suggest that the circulatory regulatory system during oscillated blood flow may be a lower dimensional homeochaotic state; thus, hemodynamic parameters must be carefully regulated when unexpected external stimuli are present.
Development and Evaluation of Antithrombogenic Centrifugal Pump: The Baylor C–Gyro Pump Eccentric Inlet Port Model
Authors: Ohara Yasuhisa , Makinouchi Kenzo , Glueck Julie , Sutherland Byron , Shimono Takatsugu , Naito Kozo , Tasai Kimitaka , Orime Yukihiko , Takatani Setsuo , Nose Yukihiko
Published: November 2008

Abstract:The Baylor C–Gyro Pump Eccentric Inlet Port Models (C1E) have been developed aiming for a longterm centrifugal ventricular assist device (VAD) as well as a cardiopulmonary bypass pump. The eccentric inlet port models are characterized by their unique inlet port and secondary impeller vanes. An inlet female pivot bearing, which was fixed to a supporting bar in the prototype model, is directly embedded into the ceiling of the pump casing. An inlet port is then placed off–center to avoid the bearing area, and it is angled between 0 to 90° from the upright position. In addition, small secondary vanes were incorporated into the impeller bottom to accelerate the washout flow behind the impeller. These features attained design objectives proposed for higher antithrombogenicity: a seal–less pump chamber, no stationary parts in the blood path, and acceleration of the secondary flow behind the impeller. The first in vivo experiment using C1E pumps showed excellent antithrombogenicity for up to 18 days when the experiment ceased due to severe infection in the calf.
Sealing of a Fabric Vascular Prosthesis with Autologous Adipose Tissue: A Preliminary Report of Its Clinical Application
Authors: Matsumoto Akihiko , Noishiki Yasuharu , Ichikawa Yukio , Soma Tamitaro , Kondo Jiro , Kosuge Takayuki
Published: November 2008

Abstract: A new method of sealing fabric vascular pros‐theses with autologous adipose tissue was clinically applied as an alternative to preclotting with fresh blood. Thirty‐six patients with peripheral arterial occlusive disease were implanted with highly porous fabric prostheses. The prostheses were prepared by sealing the fabric pores with autologous adipose tissue that had been chopped up into small pieces and enmeshed in the fabric by forceful injection of the tissue suspension through a syringe. There was no complication related to the sealed graft such as graft bleeding after implantation. In‐hospital mortality occurred in 4 patients: 1 case each of pneumonia, pulmonary infarction, sepsis, and acute myocardial infarction. During the period of 274 ± 190 days, 3 pros‐theses were found to be occluded. All the other grafts were patent. The overall patency rate was 91.4%. Postoperative angiography revealed neither intimai thickening at the anastomotic sites nor irregularity of the prosthetic surface. The method proved safe and useful for implantation of smaller caliber artificial grafts.
A Case Study with Delayed Renal Graft Function as a Consequence of Severe Secondary Hyperparathyroidism
Authors: Backman Ulla , Butler Gary , Fletchner Peter , McMullin Joseph
Published: November 2008

Abstract: A 36–year‐old Arab man had been treated with hemodialysis for 6 years. During that time he received no treatment with phosphate binders or 1,25–dihydroxy‐vitamin D3. He thus developed a severe form of secondary hyperparathyroidism and presented with bone disease, pseudoclubbing of the fingers, and soft‐tissue calcification. He was transplanted with a kidney from a living donor, but there was no immediate onset in renal function. A biopsy showed crystal deposition that was thought to be due to his secondary hyperparathyroidism. Four weeks after the renal transplantation with still no evidence of a functioning graft, a parathyroidectomy was performed. A few days later, graft function recovered, and the amount of the crystals in the kidney decreased. There is strong evidence that the severe secondary hyperparathyroidism prevented the onset of renal function. It is concluded that crystal deposition with graft dysfunction should be an absolute indication for parathyroidectomy.
In Vivo and In Vitro Evaluation of Bilirubin Removal in Postoperative Hyperbilirubinemia Patients
Authors: Usami Makoto , Nomura Hideaki , Nishimatsu Shinichi , Shiroiwa Hiroshi , Kasahara Hiroshi , Takeyama Yoshifumi , Saitoh Yoichi
Published: November 2008

Abstract: The effect of plasma adsorption (PA) on bilirubin removal by a porous type anion exchange resin (Me‐disorba BL, Kuraray) was evaluated in vitro PA and in vivo PA and plasma exchange (PE) in postoperative hyperbilirubinemia patients. Serum and plasma bilirubin were measured by routine biochemical tests, fractionated by high‐performance liquid chromatography, and its reduction and rebound were compared. In vitro and in vivo PA indicated the selectivity in bilirubin removal against measured molecules. Changes in bilirubin fractions after PA showed higher adsorbance of conjugated bilirubin (21.4–30.8%) and less adsorbance of delta (85.7%) and unconjugated bilirubin (73.7%). These differences were not observed after PE. But rebound of serum total bilirubin levels after PA was more than that after PE. It is suggested that PA by the resin is selective and has a different metabolic effect on bilirubin during and after PA as compared with PE.
Influence of the Dialyzer Membrane Material on Sodium Transport in Hemodialysis
Authors: Lopot Frantisek , Kotyk Pavel , Bláha Jan , Válek Albert
Published: November 2008

Abstract: Traditionally Gibbs‐Donnan coefficients based on the mean charge of plasma proteins are used as the only correction factor in equations describing sodium transport across the dialyzer membrane. This ignores the possible impact of the membrane material. Correction coefficients (CC) of the whole dialyzer were measured during in vivo dialysis as a quotient of dialysate to plasma sodium in an equilibrated state for different membrane materials used in commercially available dialyzers. Their mean value and correlation with total plasma protein content (TPP) were evaluated. CC for the six materials evaluated differed both in the intercept and slope of the re‐gression line CC versus TPP: Cuprophan 1: CC = 1.0253 − 0.00017 × TPP; Hemophan 1: CC = 1.119 − 0.00175 × TPP; Hemophan 2: CC = 1.095 − 0.00111 × TPP; PMMA: CC = 1.0353 − 0.00044 × TPP; SCE: CC = 1.114 − 0.00145 × TPP; and Cuprophan 1: CC = 1.0562 − 0.00065 × TPP. The observed differences are attributed to the different charge densities of the membrane materials and suggest that for a precise description of sodium transport, the role of the membrane material needs to be considered.
Growth Regulation of Endothelial Cells by Tissue Fragments: Analysis on Mechanism of Rapid Endothelialization of Tissue‐Seeded Vascular Prosthesis in a Three‐Dimensional Culture System
Authors: Mo Makoto , Noishiki Yasuharu , Kitamura Hitoshi , Kurihara Tatsuya , Kosuge Takayuki , Ichikawa Yukio , Imoto Kiyotaka , Kondo Jiro , Matsumoto Akihiko
Published: November 2008

Abstract: Rapid endothelialization of the inner surface was reported in an autologous tissue‐seeded vascular prosthesis. We applied a three‐dimensional in vitro culture system to elucidate the precise mechanism of rapid endothelial coverage of a tissue‐seeded vascular prosthesis. Human venous, omental, adipose and striated muscle tissue fragments were harvested from surgical specimens. They were embedded in collagen gel, and 2.0 times 105 bovine aortic endothelial cells (BAECs) were seeded on the gel. The number of BAECs was counted on Days 2 and 7. Growth rate of BAECs was facilitated on the collagen gel with omental and striated muscle tissue fragments (p < 0.05). Factor VIII‐negative spindle cells migrated around tissue fragments, especially around the omental and striated muscle tissue fragments. Rapid endothelialization of a tissue‐seeded vascular prosthesis may result from facilitation of EC proliferation by viable tissue fragments and migrated cells. These results confirm tissue fragments regulate EC growth, and are useful as bioengineering tools
Polyvinylidene Fluoride Monofilament Sutures: Can They Be Used Safely for Long‐Term Anastomoses in the Thoracic Aorta?
Authors: Laroche Gaétan , Marois Yves , Schwarz Erwin , Guidoin Robert , King Martin W. , Pâris Edouard , Douville Yvan
Published: November 2008

Abstract: Polyvinylidene fluoride (PVDF) represents an attractive alternative to polypropylene as a monofilament vascular suture because of its satisfactory physicochemical properties, its ease of handling, and its good biocompatibility. However, the polymer's ability to remain mechanically and chemically stable when exposed to a mild hydrolytic environment over the long term has yet to be demonstrated. One in vitro study involved the comparison of the long‐term relative resistance of PVDF and polypropylene sutures to hydrolysis for a period of 9 years. The PVDF suture showed major molecular rearrangements from the original ratio of three crystalline structures to the single β crystalline phase. The observation of some surface oxidation and water imbibition did not significantly modify the tensile strength of the PVDF suture, which retained 92.5% of its original value. In contrast, the polypropylene sample did not undergo any recrystallization but was associated with more oxidation byproducts and more water molecules near the surface, which contributed to a 46.6% loss in initial tensile strength. An in vivo study confirmed that PVDF sutures are biocompatible and are able to maintain satisfactory biostability when used to anastomose thoracic aortic allografts for a period of 6 months in the dog. The cellular reaction of fresh allografts as well as the control autografts to PVDF sutures was minimal. In other allografts that had been preserved in a supplemented medium for 1 week prior to implantation, the PVDF sutures healed satisfactorily with the formation of neocollagen and few macrophages surrounding the monofilament. No evidence of instability at the allograft‐host artery junction was observed, confirming that the PVDF sutures were able to ensure a secure anastomosis in the thoracic aorta. PVDF sutures have demonstrated superior long‐term biostability in vitro and minimal tissue response in vivo. These are two essential requirements when evaluating the use of a suture for vascular surgery in general and thoracic aortic surgery in particular
Current Issues of Continuous Ambulatory Peritoneal Dialysis
Authors: Kawaguchi Yoshindo , Hasegawa Toshio , Kubo Hitoshi , Yamamoto Hiroyasu , Nakayama Masaaki , Shigematsu Takashi
Published: November 2008

Abstract: This paper concerns the overall median technical survival of chronic continuous ambulatory peritoneal dialysis (CAPD) patients and treatment in the 6 years since the commencement of CAPD at the Jikei University Hospital. Diabetic end‐stage renal disease (ESRD) patients showed 5 years' survival, apparently shorter than that of nondiabetic ESRD which was 7 years. From this fact, the question of whether CAPD is the best dialytic option in diabetic ESRD should be reevaluated. Although a remarkable reduction in the incidence of peritonitis has been seen, generally ranging from 1 episode/40 patient months to 60 patient months or more in Japan, one serious issue still to be addressed is exit site/skin tunnel infection. The incidence is around 1 episode/30 patient months in our hospital. Discovering how to prevent this infection is a matter of some urgency. Peritoneal dialysis is a limiting dialytic modality as far as the biomembrane used. Although the precise mechanisms deteriorating the peritoneal function are still obscure, the treatment of sclerosing encapsulated peritonitis is also an urgent matter. Regarding bone disease and metastatic calcification, adynamic bone disease is frequently observed in ESRD patients. However, the pathogenesis of this morbidity has not been clarified. Treatment of extraosseous calcification in vessels and periarticular, and visceral organs should be developed. New dialytic alternatives to glucose and/or lactate‐based solutions have been under experimental study. Until a new solution is delivered commercially, CAPD will remain a transient therapy. Our large study of CAPD patients revealed that 26% were malnourished. The biochemical parameters, amount of daily protein intake, and KT/V did not show significant differences between those patients identified as well nourished versus malnourished. The causes of malnutrition should be considered from other points of view such as endocrinological circumstances. Newer therapeutic approaches to malnutrition are also required.
Hemocompatible Cellulose Dialysis Membranes Modified with Phospholipid Polymers
Authors: Ishihara Kazuhiko , Nakabayashi Nobuo
Published: November 2008

Abstract: Hemocompatibility is one of the most important properties for hemodialysis membranes. For improvement of the hemocompatibility on a cellulose dialysis membrane, modifications with new blood‐compatible phospholipid polymers were carried out. These methods included a direct grafting of the phospholipid monomer on the membrane surface, coaling the membrane surface with a water‐soluble graft copolymer composed of a cellulose backbone and phospholipid polymer as a branch, and covalent bonding with a reactive phospholipid polymer on the membrane surface. These modified membranes could reduce protein adsorption as well as complement activation and platelet adhesion on the surface without any adverse effects on the membrane performance.
Anterior Chest Wall Axillary Artery to Contralateral Axillary Vein Graft for Vascular Access in Hemodialysis
Authors: Ono Keiji , Muto Yoichi , Yano Kazuhiro , Yukizane Takashi
Published: November 2008

Abstract: Patients with end‐stage renal failure and peripheral vascular disease pose a difficult management problem in establishing long‐term angioaccess for hemodialysis. In 4 patients with access problems, we created axillary artery to contralateral axillary vein Goretex grafts. The grafts were cannulated regularly for periods ranging from 29 to 66 months without difficulty. There was one episode of thrombosis and one of congestive heart failure. The mean venous pressure was 120 mm Hg with a mean arterial flow of 220 ml/min. This type of vascular access can provide adequate blood flow in difficult patients and maintain efficient dialysis. It should be a useful addition to the armamentarium of the vascular surgeon.
The Effects and Pharmacokinetics of rhG‐CSF in Patients with Chronic Renal Failure
Authors: Akizawa Tadao , Shishido Kanji , Koshikawa Shozo
Published: November 2008

Abstract: The pharmacokinetics and effects of recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) on neutrophils and immunological function were studied in 10 patients wtih end‐stage renal failure. A single dose and 2–week consecutive dosing of 50 μ‐g/m2 of rhG‐CSF were drip infused intravenously, and plasma rhG‐CSF levels, peripheral blood cell counts, coagulation, and neutrophil and immunological functions were determined during treatment. The mean half‐life of rhG‐CSF in patients (2.47 ± 0.64 h) was prolonged to about twice that of healthy subjects, and hemodialysis did not affect the pharmacokinetics. A marked increase in neutrophils and a slight increase in lymphocytes were observed with the single and consecutive administration of rhG‐CSF, but no significant changes were noted in other leukocyte fractions and erythrocyte and platelet counts. The neutrophil alkaline phosphatase value increased significantly following rhG‐CSF administration, and other neutrophil functions were also ameliorated in several patients with neutrophil dysfunction. In consecutive administration, however, mild bone pain and increased serum alkaline phosphatase were observed in about half the patients, but neither accumulation of rhG‐CSF nor antibody production was detected. From these results, it is concluded that rhG‐CSF is safe and effective for the treatment of neutropenia and neutrophil dysfunction in patients with renal failure.
Effects of Pyridoxalated Hemoglobin Polyoxyethylene Conjugate and Other Hemoglobin‐Related Substances on Arterial Blood Pressure in Anesthetized and Conscious Rats
Authors: Kida Yoshitoshi , Maeda Midori , Iwata Seinosuke , Iwashita Yuji , Goto Keiji , Nishi Katsuhide
Published: November 2008

Abstract:The effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and other hemoglobin‐related substances on arterial blood pressure (ABP) and heart rate (HR) were examined. Infusion of PHP and other hemoglobin‐related substances elevated ABP and increased HR. The degree of the increase in ABP and HR did not differ among the groups. There were species' differences in responses to PHP. Pretreatment with various blockers did not abolish the elevation of ABP. The pretreatment of NG‐monomethyl‐l‐arginine dose‐dependently reduced the elevation of ABP but did not completely abolish it. PHP also elevated ABP in conscious rats. The magnitude of the ABP elevation was significantly smaller than in the anesthetized rats. Results indicate that inhibition of nitric oxide (NO) might be responsible in part for the elevation of ABP, and the degree of the elevation would be dependent on the degree of contribution of NO to the regulation of ABP.
An Effective LDL Removal Filter for the Treatment of Hyperlipidemia
Authors: Matsuda Yukihiro , Sueoka Akinori , Nose Yukihiko
Published: November 2008

Abstract: On‐line membrane plasma fractionation techniques have made semiselective removal of pathological macromolecules practical. However, several problems such as cryogel formation exist when the procedure is performed at ambient temperature. Cryogel formation takes place when heparinized plasma is cooled below 35°C and when it tends to occlude the pore structure of the secondary filter membrane resulting in a poor molecular cut off of the macromolecular filter. Thermofiltration is one of the on‐line plasma fractionation techniques used when warming plasma from 37 to 42°C to prevent cryogel formation. Thermofiltration enhanced the performance of the lipofilter (Kuraray 4A) and demonstrated better molecular cut off between low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol than double filtration plasmapheresis (DFPP). An improved lipofilter (Kuraray 5A) has been developed and has shown better molecular cut off between LDL cholesterol and HDL cholesterol than the 4A filter. However, cryogel formation still occurred even using the 5A filter during the DFPP procedure. Thermofiltration maintains the performance of the secondary filter by preventing cryogel formation. Further studies are required to evaluate the enhanced performance of the 5 A filter by thermofiltration.
High Cell‐Density Culture System of Hepatocytes Entrapped in a Three‐Dimensional Hollow Fiber Module with Collagen Gel
Authors: Takeshita Kazuyoshi , Ishibashi Haruaki , Suzuki Masayuki , Yamamoto Takumi , Akaike Toshihiro , Kodama Masashi
Published: November 2008

Abstract: A compact three‐dimensional (3D) module is needed for hepatocyte culture in order to develop an effective hybrid artificial liver system that can retain hepa‐tocellular structure and differentiated functions. We treated the 3D module with collagen gel to entrap rat hepatocytes. This method yielded a high hepatocellular density (2 times 107 cells/ml) over a period of 14 days and maintained the secretion of albumin and ureogenesis at the same level as the control monolayer method. The ammonia removal remained at 43% of the Day 0 value over 8 days of perfusion. Our data show that this approach may be useful for liver support therapy in an ex‐tracorporeal circuit.
Present Trends in Clinical Experience with Dynamic Cardiomyoplasty
Authors: Moreira Luiz Felipe P. , Bocchi Edimar A. , Bacal Fernando , Stolf Noedir A. G. , Bellotti Giovanni , Jatene Adib D.
Published: November 2008

Abstract: Dynamic cardiomyoplasty has been performed to reinforce the myocardium in the treatment of patients with severe cardiomyopathies. At the Heart Institute of S˜o Paulo University Medical School, 36 patients were submitted to cardiomyoplasty between May 1988 and December 1993. The indications were idiopathic dilated car‐diomyopathy in 31, ischemic cardiomyopathy in 3, and Chagas' disease cardiomyopathy in 2 patients. Twenty‐eight patients were categorized in New York Heart Association (NYHA) Class III and 8 in Class IV despite the use of maximal medical therapy. There were no hospital deaths, and patients were followed up from 2 to 70 months (mean, 24 months). Besides the improvement of NYHA functional class from 3.2 ± 0.6 to 1.6 ± 0.9 at 6 months of follow‐up, patients also presented significant changes in the left ventricular systolic and diastolic functions. Nevertheless, 16 patients died, and 2 patients were submitted to heart transplantation during late follow‐up. Actuarial survival rates were 82.3% at 1 year, 61.5% at 2 years, and 38.8% at 5 years of follow‐up. Otherwise, the analysis of factors influencing the outcome showed that long‐term survival was significantly affected by preoper‐ative functional class and by pulmonary vascular resistance. The 26 patients operated in NYHA functional Class III and with pulmonary vascular resistance below 4 Wood units presented survival rates of 72.7% at 2 years and of 63% at 5 years of follow‐up. In conclusion dynamic cardiomyoplasty improves functional class and left ventricular function in patients with severe cardiomyopathies. However, the long‐term survival after this surgical procedure may be limited by the patients' condition before the operation.
Biocompatibility in Hemodialysis: Clinical Relevance in 1995
Authors: Shaldon Stanley , Koch Karl Martin
Published: November 2008

Abstract: Hemodialysis therapy for end‐stage renal disease is still empirical even after more than 30 years of experience. Although long‐term survival can now be assured in selected patients, clinical results tend to be disappointing. Hemodialysis therapy needs to be improved. Zealots of the biocompatibility school believe that this improvement will come from reducing undesirable consequences of blood membrane interaction, particularly complement activation. However, there is controversy over the clinical meaningfulness of biocompatibility when exclusively related to blood membrane interactions. Another dimension needs to be added, namely ultrapure di‐alysate to avoid subclinical chronic effects of activation of the cytokine cascade by bacterial fragments present in dialysate. While the pathogenesis of acute anaphylactoid reactions are understood and largely preventable, the relation of the chronic syndromes such as amyloidosis to the use of a particular membrane remain unproven. Prospective studies that will occupy at least a decade will be necessary to decide these issues.
Hemodiafiltration in Two Chambers Without Replacement Fluid: A Clinical Study
Authors: Sanz‐Moreno C. , Botella J.
Published: November 2008

Abstract: Paired filtration dialysis (PFD) is the only hemodiafiltration (HDF) technique in which ultrafiltrate (Uf) is obtained continuously with a similar composition to plasma. It has been proved that Uf is regenerated when it passes through an uncoated adsorbent charcoal cartridge: this one removes medium‐to‐large solutes and small toxines (except for urea and phosphates), but not the electrolytes and bicarbonate. This regenerated Uf can be used like replacement fluid, using the same Uf pump as the infusion pump; this makes the HDF technique easier and more reliable. During 12 months (3 h/3 sessions/ week), we treated 13 patients with this PFD‐Charcoal technique. These patients were previously on conventional PFD for at least 6 months. The biochemical results were excellent with a stabilization of all parameters (urea, creatinine, uric acid, Na, K, Cl, Ca, phosphates, β2‐microglobulin, β2M, etc.) and a better control of acidosis (statistically significative after 6 months). The clinical tolerance was also excellent, and the technique was greatly simplified. We conclude that PFD‐Charcoal is a good HDF technique that avoids the use of exogenous replacement fluid by using the regenerated Uf itself as an endogenous substitution fluid with bicarbonate.
Kinetic Analysis of UDP‐Glucuronosyltransferase in Bilirubin Conjugation by Encapsulated Hepatocytes for Transplantation into Gunn Rats
Authors: Bruni Silvia , Chang Thomas Ming Swi
Published: November 2008

Abstract: Kinetic analysis of the enzyme UDP‐glucuronosyltransferase (UDPGT), responsible for the conjugation of bilirubin, suggests that it is a multisubunit enzyme in which there is cooperative binding of the substrate to the subunits. The binding of bilirubin to UDPGT shows positive cooperativity with an apparent Hill coefficient of 2.9. The binding of UDP‐glucuronic acid (UDPGA) exhibits kinetics with mixed cooperativity with an apparent Hill coefficient of 4.028. Homogenized rat hepatocytes, intact hepatocytes, and hepatocytes encapsulated in alginate‐polylysine‐alginate artificial cells, when incubated with bilirubin (1.6 mM) and UDPGA (20 mM), can form monoconjugated and diconjugated bilirubin. However, the presence of the artificial membrane offers some mass transfer resistance. The intraperitoneal transplantation into the Gunn rat of free and microencap‐sulated Wistar rat hepatocytes shows that both are equally effective in lowering the serum bilirubin. Thus, the membrane did not contribute to a lowering of efficacy after transplantation.
Clinical Trials of Immunoadsorbent in Systemic Lupus Erythematosus Therapy
Authors: Gao Chun‐Li , Li Bao‐An , Chen Chang‐Zhi , Yu Yao‐Ting , Yuan Ping , Song Ji‐Chang
Published: November 2008

Abstract: Five patients with systemic lupus erythematosus (SLE) were perfused through an extracorporeal shunt filled with DNA‐immunoadsorbent (DNA immobilized on carbonized resin beads). High concentrations of anti‐DNA antibodies (36.4–67.0%) (binding percentage with 125I‐DNA) in the serum of SLE patients were reduced to 13.8–53.0%, respectively. The highest removal percentage was 62.1%. Although the decline levels varied, the symptoms of patients, i.e., long‐term severe joint pain, severe edema, hydropericardium, and ascites were all relieved considerably. The immunoadsorbent showed satisfactory blood compatibility.
Lactate Versus Bicarbonate On‐Line Hemofiltration: A Comparative Study
Authors: Marangoni Roberto , Civardi Fernando , Masi Francesco , Savino Renato , Cimino Roberto , Colombo Roberto , Maltagliati Luca
Published: November 2008

Abstract: In this study, 6 chronic anuric uremic patients underwent lactate hemofiltration (HF) with a substitution fluid, prepared in bags, for 3 months and bicarbonate HF, with continuous on‐line preparation of the substitution fluid, for 3 months. We determined Na+, Cl‐, K+, total calcium (Ca), ionized calcium (Ca2+), phosphate, intact parathormone (I‐PTH), pH, Pco2, Po2, and HCO3‐ in plasma before, during, and after the treatment, as well as Ca, Ca2+, phosphate, and I‐PTH in the ultrafiltrate. Moreover, heart rate (HR) and mean arterial pressure (MAP) were continually recorded during the procedure. Furthermore, the patients underwent echocardiographic study before and after the session. In comparison with lactate, bicarbonate HF caused a significant increase in HCO3‐ and a decrease in K+ plasma concentrations. This was detectable, with lower significance, even 44 h after the end of the treatment. At the end of the long interdialytic period (68 h after the end of the treatment), no significant difference was detectable. pH and Pco2 showed a significant but transient increase during HF. The other parameters investigated did not differ significantly between the two methods.
The Role of Plasma Exchange in the Treatment of Severe Forms of Hemolytic‐Uremic Syndrome in Childhood
Authors: Slaviček Jasna , Puretić Zvonimir , Novak Milivoj , Sarnavka Vladimir , Benjak Vesna , Glavaš‐Boras Snežana , Thune Sigmund
Published: November 2008

Abstract: Therapeutic plasma exchange (PE) or plasma‐pheresis has been used in recent years in the treatment of severe hemolytic uremic syndrome (HUS) in children. We analyzed the benefit of PE and peritoneal dialysis (PD) in 9 children, 6 boys and 3 girls, aged 1–10 years, from 1983–1993. All children came from different geographical regions, and all had the sporadic form of the illness. Three patients had the gastrointestinal form, 5 had respiratory prodromes while 1 child developed HUS during the course of varicella. Seven children were hypertensive, but only in 3 was hypertension persistent. The child with varicella had a transient complement decrease. Five children were treated with PE. In 4 children, fresh frozen plasma (FFP) was used as replacement fluid, and human albumin was used in 1 child. Four children were treated with PD and infusions of FFP. Rapid recovery of renal function was observed in 5 patients whereas in 2 oliguric children the recovery of renal function ensued within 1 and 2 months, respectively. Two children developed terminal renal failure (TRF) (in 1 child the treatment was very delayed, and in the other child HUS developed following varicella). Only 1 boy had relapses of the disease followed by impairment of renal function from which he gradually recovered. During the 3–10 year follow‐up period, only the child with relapses was hypertensive while the others had normal clinical and laboratory parameters. We suggest that PE plays an important role in the early treatment of severe forms of HUS in children.
Intraarterial Perfusion of the Hindlimb with Pyridoxalated Hemoglobin Polyoxyethylene Conjugate Solution in Anesthetized Dogs
Authors: Kida Yoshitoshi , Yamakawa Takashi , Iwasaki Shuichi , Furusho Nobuyuki , Kadowaki Yoshihiro , Iwata Seinosuke , Iwashita Yuji , Nishi Katsuhide
Published: November 2008

Abstract: To evaluate the potential clinical usefulness of a modified hemoglobin, pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), the hindlimb vascular bed was perfused with PHP solution while monitoring tissue oxygen tension (Pto2) in anesthetized dogs. The hindlimb region was perfused through the external iliac artery with a roller pump at a varying perfusion rate. Pto2 was measured using a Po2‐monitoring probe inserted into the gra‐cial muscle. After surgical preparation for perfusion, the iliac arterial flow rate was 19.9 ± 5.6 ml/min, and baseline Pto2 was 38.4 ±1.3 mm Hg. Perfusion with autologous arterial blood with the pump increased Pto2 and perfusion pressure (PP) in a perfusion rate‐dependent manner. Perfusion with PHP solution at 20 ml/min decreased Pto2 from the initial baseline level, but an increase in the flow rate to 40–55 ml/min restored or induced an elevation of Pto2. Results demonstrated that PHP solution can deliver oxygen to local tissue and maintain tissue oxygen tension at the same level as autologous arterial blood at a high enough flow rate.
Kinetics of Phenols in Body Fluid Compartments During Hemodialysis
Authors: Erben Josef , Schück Ota , Brátová Miluše , Moučka Peter , Palička Vladimír , Fixa Petr , Hájková Božena , Herout Vladimír , Štilec Roman , Zahradník Jiří
Published: November 2008

Abstract: On the basis of direct quantification of hemodialysis (HD), the kinetics of phenols (Ph) were followed in 13 patients on regular HD treatment. The average plasma levels of Ph before and after HD were 627 ± 109 μmol/L and 416 ± 81 μmol/L, respectively. The total amount of Ph removed during 5‐h HD was 7,481 ± 1,894 μmol. For calculation of the generation rate (G), a new formula has been derived not requiring knowledge of the corresponding volume of distribution. The G of Ph was 2.9 ± 0.7 μmol/min on average. The mean dialysis clearance (K) of Ph was 48.2 ± 10.2 ml/min.
Model for a General Mechanical Blood Damage Prediction
Authors: Bludszuweit C.
Published: November 2008

Abstract: Knowledge of the correlation between mechanical loading of formed blood elements and the amount of their destruction is important for the prediction of blood trauma in artificial circulatory devices as well as in natural circulation. A hemodynamic assessment and optimization of artificial organs to minimize trauma could be undertaken in the design phase given a comprehensive mechanical blood damage model. A theory to determine blood trauma theoretically as a combination of a mechanical loading analysis and a phenomenological blood damage resistance hypothesis is presented. Arbitrary stress‐time functions of blood particles predicted by flow analysis are reduced to a set of simple time functions for which the damage behavior may, in principle, be obtained from mechanical blood damage tests. A classification of those stress functions into damaging and nondamaging parts is followed by an overall trauma prediction considering cumulative effects by means of a damage accumulation hypothesis. Theoretical determination of blood destruction caused by mechanical stresses in a centrifugal pump is one possible application of the proposed theory. The strategy of hemolysis prediction is demonstrated for the Aries Medical Isoflow Pump. Irregular stress‐time loading functions of particles passing the pump domain obtained by three‐dimensional numerical flow simulations were reduced and classified into harmonic components. To relate these functions to their hemolytic response can only be done in a qualitative manner since blood damage behavior under transient stress loading has not been sufficiently investigated. Accurate prediction of blood trauma using the proposed theory will require detailed study of the influence of frequency and amplitude of harmonic stress loading on formed blood elements.
Three‐Dimensional Numerical Prediction of Stress Loading of Blood Particles in a Centrifugal Pump
Authors: Bludszuweit C.
Published: November 2008

Abstract: The successful use of centrifugal pumps as temporary cardiac assist devices strongly depends on their degree of blood trauma. The mechanical stress loading experienced by cellular components on their passage through the pump is a major cause of blood trauma. Prediction of the mechanical stresses will assist optimization of pump design to minimize hemolysis and platelet activation. As a theoretical approach to this task, the determination of the complete three‐dimensional (3D) flow field including all regions of high shear stress is therefore required. A computational fluid dynamics (CFD) software package, TASCflow, was used to model flow within a commercially available pump, the Aries Medical Iso‐flow Pump. This pump was selected in order to demonstrate the ability of the CFD software to handle complex impeller geometries. A turbulence model was included, and the Newtonian as well as the Reynolds stress tensor calculated for each nodal point. A novel aspect was the assignment of scalar stress values to streaklines representing particle paths through the pump. Scalar stress values were obtained by formulating a theory that enables the comparison of a three‐dimensional state of stress with a uniaxial stress as applied in all mechanical blood damage tests. Stress loading‐time functions for fluid particles passing inlet, impeller, and outlet domains of the pump were obtained. These showed that particles undergo a complex, irregularly fluctuating stress loading. Future blood damage theories would have to consider an unsteady stress loading regime that realistically reflects the flow conditions occurring within the pump. Validation of the pump flow modeling is demonstrated with pressure head discrepancies predicted to be within 15% of measured values.
Biomaterials for Rotary Blood Pumps
Authors: van Oeveren W.
Published: November 2008

Abstract: Rotary blood pumps are used for cardiac assist and cardiopulmonary support since mechanical blood damage is less than with conventional roller pumps. The high shear rate in the rotary pump and the reduced anti‐coagulation of the patient during prolonged pumping enforces high demands on the biocompatibility of the materials in the pump in order to prevent thrombus formation. Materials with a very hydrophobic character appear to adsorb much thrombin and induce a conformational change of fibrinogen, resulting in a surface with a high affinity for platelet interaction. Furthermore, heigh shear forces of 120 dyne‐s‐cm2 in rotary pumps induce platelet release and platelet aggregation. Thus, hydrophobic materials and high shear rates should be prevented to avoid thrombus formation in rotary blood pumps.
A Preliminary Flow Visualization Study in a Multiple Disk Centrifugal Artificial Ventricle
Authors: Miller G.E. , Madigan M. , Fink R.
Published: November 2008

Abstract: Flow patterns in a multiple disk centrifugal pump were analyzed so that the device could be incorporated as a ventricular assist or a bridge‐to‐transplant device. The pump operates either in pulsatile or steady flow modes with the ability to change modes within a fraction of a second. The pump was tested on a mock circulatory system consisting of an arterial fluid capacitor, a systemic resistor, and a venous capacitor. Arterial volume flow rate, arterial pressure, inlet (venous) pressure, and pump rotation speed are continually monitored. A glycerin/ water solution is used as a blood analog. Flow visualization was performed with a 3 mW yellow laser, sheet lens, neutrally buoyant amberlite particles, and both still and motion picture photography. Flow patterns matched theoretical predictions very well; inlet flow spread radially outward through the disk annular spaces while propelled by shear and centrifugal forces.
Current Strategy for Severe Heart Failure with Mechanical Circulatory Support
Authors: Koyanagi Hitoshi , Kitamura Masaya , Nishida Hiroshi , Hachida Mitsuhiro , Endo Masahiro , Hashimoto Akimasa
Published: November 2008

Abstract: In the last 10 years, 37 patients received assisted circulation or a ventricular assist device after open‐heart operations at the Heart Institute of Japan. After cardiovascular surgery, 12 patients underwent venoarte‐rial bypass (VAB), 13 had biventricular bypass (BVB), 8 had left ventricular bypass (LVB), and the remaining 4 received a left ventricular assist device (LVAD). Weaning and discharge rates of the patients by type of circulatory supports were 41.7 and 25.0% with VAB, 69.3 and 46.2% with BVB, 87.5 and 37.5% with LVB, 75.0 and 50.0% with LVAD, and 44.4 and 11.1% with PCPS, respectively. Concerning complications of postcardiotomy circulatory support, hemorrhage and ventricular arrhythmia postcardiotomy circulatory support, hemorrhage, and ventricular arrhythmia (immature weaning) decreased with low‐heparinized isolated left ventricular supports (i.e., LVB, LVAD). However, profound biventricular failure, infection, and multiple organ failure remain as possible complications with any type of assisted circulation. These results suggest that early application of circulatory support and appropriate selection of the mode of support and devices used are important for successful circulatory support.