bluuebunny/crossref_metadata_2025 huggingface dataset:
Apheresis-Elutriation Program for Adoptive Immunotherapy with Autologous Activated Monocytes in Cancer Patients
Authors: Faradji A. , Bohbot A. , Schmitt-Goguel M. , Dumont S. , Eischen A. , Wiesel M.L. , Stierle A. , Follea G. , Eber M. , Bergerat J.P. , Bartholeyns J. , Poindron P. , Witz J.P. , Frost H. , Oberling F.
Published: March 2018

Human blood monocytes (Mo) and monocyte-derived macrophages (MØ) are known to be potent antitumor cytotoxic effector cells through activation with recombinant human interferon gamma (rIFN-y), bacterial muramyldipeptide or the synthetic derivative muramyltripeptide phosphatidylethanolamine entrapped in liposomes (L-MTP-PE). Large-scale generation of ex vivo activated Mo from the blood of cancer patients proved feasible. We report our experience with a fixed rotor speed counterflow centrifugation elutration (CEE) procedure using the newly available Beckman high capacity JE-5.0 rotor system that reproducibly isolates up to 1.0-1.5×109 Mo with > 90% purity, in suspension and functionally intact derived from peripheral blood mononuclear cell-enriched suspensions obtained by leukapheresis (LP) from healthy volunteers and cancer patients. The semiclosed, easy to handle CCE system, was adapted to a sterile technique that permitted clinical trials in adoptive monocyte immunotherapy. Freshly isolated Mo did not lose morphological or functional integrity and had no spontaneous activation. Their abilities to become activated to the cytotoxic state after 18-h stimulation with 500 U/ml rIFN-γ or 1 μg/ml L-MTP-PE and to differentiate into matured MØ in vitro were not altered.

The system was therefore used to isolate large numbers of Mo for a phase I clinical trial of intraperitoneal immunotherapy with L-MTP-PE activated autologous Mo in nine patients with peritoneal carcinomatosis. Each patient received weekly Mo infusions (n=5) with an intrapatient dose escalation schedule (from 107 to 109 Mo). Toxicities were mild including fever, chills and abdominal pain. There was no treatment-induced thromboembolic event or capillary leak syndrome. The degree of Mo activation in vitro was shown by the release of procoagulant activity and monokines (IL-1, TN Fa and IL-6) in the culture supernatants and the antitumor activity against U937 cells and human ovarian carcinoma cells in vitro and in tumor-bearing nude mice in vivo. The in vivo immunomodulatory activity of i.p. infused Mo was demonstrated by an elevation of WBC and granulocyte counts, fibrinogen, C-reactive protein and neopterin in peripheral blood and generation of IL-1, TFNa and IL-6 in peritoneal fluid. Phase II clinical trials, now in progress, should further define the therapeutic potential of human adoptive cellular immunotherapy using Mo or MØ.
Kidney Transplantation from Elderly Living Donors
Authors: Haberal M. , Sert Ş , Altunkan Ş , Gülay H. , Hamaloğlu E. , Bulut O.
Published: March 2018

Because of the inadequate numbers of organ donors, transplant surgeons are obliged to search for new horizons. Also, traditional beliefs are changing. The shortage of organs for transplantation, has led us to try certain arrangements so that suitable elderly organ donors may be included, as in many other transplant centers. We have now done 34 kidney transplantations from living related donors, who were 60 years of age and older. Donor-specific transfusions and low-dose triple drugs were used for all recipients. The overall patient survival was 97.5% and graft survival was 85.29%. In the light of these results we conclude that elderly living donor kidneys can be used satisfactorily with low-dose triple therapy.
Prosthetic Heart Valve Evaluation in Vitro: Critical Aspects of Data Comparability
Authors: Barbaro V. , Bartolini P. , Daniele C. , Grigioni M. , Palombo A.
Published: March 2018

The technology of heart valve substitution has considerably improved in the last few years, but its reliability after implantation is still not good enough, hence the need to study new valve design and improve quality testing. Different pulse duplicators are used for heart valve testing, but the results depend very much on the system adopted and the measurement protocol.

Tests on two pulse duplicators currently used at the Biomedical Engineering Laboratory at the Istituto Superiore di Sanità, Rome, are reported here. The most significant parameters for valve evaluation were measured following each system's own protocol. Attention was focused on vascular load tuning when setting up the system and on the relationship between drive unit flow waveform and valve regurgitation and energy loss measurements. Standardization criteria must be defined in order to ensure the reliable comparability of in vitro testing results.
Evaluation of Vibrated Fluidized Bed Techniques in Coating Hemosorbents
Authors: Morley D.B.
Published: March 2018

A coating technique employing a vibrated fluidized bed was used to apply an ultrathin (2 μm) cellulose nitrate coating to synthetic bead activated charcoal. In vitro characteristics of the resulting coated sorbent, including permeability to model small and middle molecules, and mechanical integrity, were evaluated to determine the suitability of the process in coating granular sorbents used in hemoperfusion. Initial tests suggest the VFB-applied CN coating is both highly uniform and tightly adherent and warrants further investigation as a hemosorbent coating.
Effects of Recombinant Human Erythropoietin on the Plasma Levels of Vasoactive Regulatory Peptides in Patients on Maintenance Hemodialysis
Authors: Hegbrant J. , Thysell H. , Ekman R.
Published: March 2018

The plasma levels of nine vasoactive regulatory peptides were measured by radioimmunoassay in six stable patients with chronic renal failure on regular hemodialysis, before and during treatment with recombinant human erythropoietin (r-huEPO). All patients responded with significant increases in hemoglobin concentrations and hematocrit. Mean arterial blood pressure was not significantly changed nor were there any changes of body weight or interdialytic body weight gain. The mean plasma levels of atrial natriuretic peptide and motilin decreased significantly, by 38 and 16 percent respectively, during r-huEPO treatment. There were no changes in mean plasma levels of arginine vasopressin, calcitonin gene-related peptide, β-lipotropin, γ2-melanocyte-stimulating hormone, neuropeptide Y, substance P or vasoactive intestinal peptide. No significant correlations were observed between changes of plasma peptide levels and changes of mean arterial blood pressure.
Peritoneal Dialysis using Bicarbonate-Containing Solution Sterilized by Ultrafiltration
Authors: Yu A.W. , Manahan F.J. , Filkins J.P. , Mohammed M.S. , Soundararajan R. , Mcshane A.P. , Gandhi V.C. , Ing T.S.
Published: March 2018

We performed acute peritoneal dialysis on eight end-stage renal disease patients using a bicarbonate-containing solution sterilized by ultrafiltration through polyamide filters. The patients tolerated the procedure well; their azotemia and metabolic acidosis improved.
Temporary Mechanical Circulatory Support for Severe Cardiac Failure: Experimental Study
Authors: Fischer E.I. Cabrera , Chachques J.C. , Garcia A. , Pichel R.H. , Morales M.C. , Carpentier A.
Published: March 2018

We describe a technique for mechanical cardiac assistance in an acute model of severe cardiac failure. Cardiac dysfunction was induced by a high dose of halothane in 13 dogs. Seven served as controls. Following median sternotomy, a pneumatically driven device was implanted in the other six dogs in a para-aortic position, using a simple surgical technique without cardiopulmonary bypass. The aorta was cross-clamped during cardiac assistance. During hemodynamic studies, the seven control animals with induced cardiac failure showed high end-diastolic left ventricular and right atrial pressures with low cardiac index and systolic left ventricular and aortic pressures. All dogs in this group died within 30 minutes. Use of a monovalvular cardiac assist device in the experimental group of six dogs to pump blood from the aortic root to the descending aorta in a counterpulsation manner, confirmed good preservation of systemic hemodynamic parameters after induction of heart failure. All animals in this treated group survived more than 45 minutes. Hemodynamically, the device acts as a new ventricle and the impaired left ventricle functionally becomes a left atrium. This condition is clinically appropriate for recovery of left ventricular function in severe acute myocardial failure.
Implantable Glucose Sensors: Comparison between in Vitro and in Vivo Kinetics
Authors: Von Woedtke T. , Fischer U. , Brunstein E. , Rebrin K. , Abel P.
Published: March 2018

This study was aimed at validating the in vitro estimated response characteristics of implanted glucose oxidase/H2O2 electrodes with respect to their in vivo function. Mono-exponential non-linear regression analysis of sensor current vs. time curves in response to square alterations in glucose concentration gave response times T95 of between 1 and 5 min. Non-primed glucose infusions were applied to dogs with these electrodes implanted subcutaneously. The simultaneously monitored in vivo data were subjected to non-linear regression analysis. The time constants T of increases or decreases after starting or ending the glucose load were (mean ± SEM) 53 ± 10 and 26 ± 4 min (significant difference, p < 0.05) in sensor current, 28 ± 8 and 15 ± 2 min (NS) in whole blood, and 26 ± 5 and 18 ± 2 min (NS) in plasma. The in vivo kinetic patterns of sensors were not related to their in vitro response times. Non-linear regression analysis of in vitro responses of glucose sensors under clearly defined conditions is recommended as a basis for further studies. The physiological delay in the subcutaneous glucose system needs more attention in this field of research.
Inhibition of Complement Activation with EDTA in Vivo during Sham Hemodialysis
Authors: Kandus A. , Benedik M. , Bren A.F. , Drinovec J. , Fliser D. , Knap B. , Kladnik S. , Ivanovich P.
Published: March 2018

To check whether in vivo EDTA prevents complement activation resulting from blood contact with the dialyzer membrane, sham hemodialysis (HD) was performed in seven healthy volunteers using Cuprophan hollow-fiber dialyzers. Blood samples were drawn from the arterial and venous blood lines of the dialyzer before and after EDTA was infused into the arterial line. Venous line plasma C3a concentrations before EDTA infusion were significantly higher than after EDTA. Also, venous line plasma C3a concentrations before and after EDTA infusion were significantly higher than in the arterial line.

These results indicate that complement activation can be attenuated by EDTA during sham HD. Technical improvements in the procedure may permit complete inhibition of complement activation.
Plasma Exchange (Pe) Treatment in Drug-Induced Toxic Epidermal Necrolysis (Ten)
Authors: Sakellariou G. , Koukoudis P. , Karpouzas J. , Alexopoulos E. , Papadopoulou D. , Chrisomalis F. , Skenteris N. , Tsakaris D. , Papadimitriou M.
Published: March 2018

Toxic epidermal necrolysis (TEN) or Lyell's syndrome is a rare fulminating skin disease notorious for its rapidly progressive course and high mortality rate. TEN is characterized by the sudden onset of epithelial necrosis of skin with frequently associated involvement of the gastrointestinal, genitourinary tract and bronchopulmonary linings.

We describe the clinical course of five patients with severe drug-induced TEN, treated with PE. The suspected drugs were carbamazepine in one patient, paracetamol in one, a combination of paracetamol and mefenamic acid in one, allopurinol in one and ciprofloxacin in one. Three had a skin involvement affecting almost the entire surface of the body. In addition to the skin lesions, mouth, esophagus and lungs were also involved. Steroids proved ineffective. PE was carried out because of the rapid deterioration of the clinical picture. The mean number of PE sessions was 3.22 (range 1-5). Complete remission of the syndrome was achieved in four patients. One patient died due to septic shock.

As so far there is no treatment of proven value for this condition, controlled trials should be set up in order to assess the value of PE in TEN.
A Randomized Trial of Plasmapheresis and Subsequent Pulse Cyclophosphamide in Severe Lupus: Design of the Lpsg Trial
Authors: Euler H.H. , Schroeder J.O. , Zeuner R.A. , Teske E.
Published: March 2018

A group of clinics cooperating as the Lupus Plasmapheresis Study Group (LPSG) is starting an international multicenter study of the treatment of severe systemic lupus erythematosus. The primary goal of this randomized and prospective trial is to establish whether treatment with plasmapheresis and subsequent pulse cyclophosphamide improves the outcome compared to treatment with pulse cyclophosphamide alone.

The underlying rationale assumes that plasmapheresis: a) eliminates pathogenic autoantibodies and immune complexes and b) induces a compensatory activation of pathogenic lymphocyte clones through a feedback between circulating antibodies and their respective antibody-producing clones. Synchronization of plasmapheresis with subsequent pulse cyclophosphamide should enhance the deletion of pathogenic clones during the period of greatest vulnerability.

This overview reviews the first results of treatment approaches based on this concept and summarizes the design of the LPSG trial
New J-3 Flexible-Leaflet Polyurethane Heart Valve Prosthesis with Improved Hydrodynamic Performance
Authors: Jansen J. , Willeke S. , Reiners B. , Harbott P. , Reul H. , Rau G.
Published: March 2018

The aim of this new three-leaflet valve development was to design a leaflet with minimum membrane stresses during performance. This is achieved by manufacturing the valve leaflets shaped almost flat in a medium opening position. Thus, the leaflets have two stable positions, one with maximum opening area and the other with favorable stress distribution in the closed position. The transition between the two end positions is achieved through a two-dimensional rolling motion without buckling and with minimum membrane stresses (bulge forces). The manufacturing technique is dip-coating in polyurethane.

Hydrodynamic evaluation of the J-3 valve in steady and pulsatile flow showed minimum pressure drop compared to other commercially available valves. Laser-Doppler-anemometry studies indicated very low shear stresses in the flow field downstream of the valve. In durability tests prototypes have reached lifetimes of up to 17 years.

In conclusion, the J-3 valve shows superior hydrodynamic performance thereby reducing potential thrombus formation. Minimization of stresses within the valve leaflets through design could reduce calcification.
Tfe-Plasma Polymerized Dermal Sheep Collagen for the Repair of Abdominal Wall Defects
Authors: Van Der Laan J.S. , Lopez G.P. , Van Wachem P.B. , Nieuwenhuis P. , Ratner B.D. , Bleichrodt R.P. , Schakenraad J.M.
Published: March 2018

The aim of this study was to design and evaluate a degradable biomaterial for the repair of abdominal wall defects. Hexamethylenediisocyanate-tanned dermal sheep collagen (HDSC) was plasma-polymerized with tetrafluoroethylene (TFE) which resulted in a hydrophobic surface on the visceral side (TFE-HDSC). Full-thickness abdominal wall defects were made in rats and repaired with HDSC or TFE-HDSC implants.

Unmodified HDSC implants showed excellent fixation to the adjacent muscle tissue but intestinal adhesions were observed. These implants showed insufficient strength after four weeks, illustrated by bulging of the peritoneal contents (herniation). Plasma-polymerized implants after four weeks of implantation showed firm incorporation into the surrounding muscle tissue. With one exception there were no bowel adhesions. Fewer herniations were observed, indicating a prolonged degradation period. Further studies on the optimalization of degradation time are in progress.
The Simultaneous Measurement of Glomerular Filtration Rate (Gfr) and Renal Plasma Flow (Rpf) following Renal Transplantation by use of Functional Imaging
Authors: Burrows L. , Stritzke P. , Kupfer S.
Published: March 2018

A new method for evaluating renal function using dynamic scintigraphy and deconvolution is described; functional images can be created from the data to quantitate kidney function. Our data are indicating that GFR measurements obtained by this method do not differ from those obtained by classical renal clearance methods. As was expected measurements of renal plasma flow exceed the values of PAH clearance. Additional studies to determine extraction ratios must be done along with direct flow meter measurements.
Filtration of Dialysate Using An On-Line Dialysate Filter
Authors: Frinak S. , Polaschegg H-D. , Levin N.W. , Pohlod D.J. , Dumler F. , Saravolatz L.D.
Published: March 2018

Increased concerns about pyrogenic contamination of dialysate have led to the development of an on-line dialysate filtration system. Bacteriological testing of the system was performed (n=6) by introducing bicarbonate concentrate contaminated with E. coli 026:B 6 (3x109 cfu/ml) into a dialysis machine equipped with a two-stage polysulfone filtration system. The bacterial concentration of the dialysate entering the filtration system was maintained above 106 cfu/ml and endotoxin levels ranged from 30-300 ng/ml during the 3-hour test period. Bacterial and endotoxin levels on the input side of the first-stage filter reached minimum concentrations of 5.4x109 cfu/ml and 30,000 ng/ml respectively. All output samples of filtered dialysate showed no bacterial growth and endotoxin levels were below the sensitivity (0.003 ng/ml) of the LAL assay. A dialysis machine (QD = 500), equipped with a single stage filtration system, was used for 18 months of clinical testing. In order to evaluate the system's reliability with regard to membrane failures and reduced dialysate flow, filter membrane integrity was verified weekly using a pressure holding test and dialysate flow was measured under routine clinical conditions. No membrane failures occurred, and dialysate flow was maintained at 511 ± 17 ml/min (n=70) during the test period. In conclusion: dialysate filtration is an effective and practical method for prevention of pyrogenic reactions due to high levels of bacteria and endotoxins.
Shear Stress Related Blood Damage along the Cusp of a Tri-Leaflet Prosthetic Valve
Authors: Einav S. , Reul H. , Rau G. , Elad D.
Published: March 2018

Blood flowing through a prosthetic heart valve can be damaged by flow-induced shear forces. Fluid dynamics variables and geometric factors play an important role in the evaluation of shear-stress-related blood damage. Central-flow prosthetic valves have been considered as an optimal replacement for mechanical and biological valves. Recently it was shown that shear stress distribution along the surface of a polyurethane cusp reaches values that can damage the blood elements. A mathematical model correlating the effects of shear stresses on blood corpuscles with clinical findings was employed in vitro. The model can be applied to the effects of blood-surface interaction and is of clinical relevance
An Insulin-Releasing System Responsive to Glucose: Thermodynamic Evaluation of Permeability Properties
Authors: Casolaro M. , Barbucci R.
Published: March 2018

Two weak poly(acid)s, poly(acrylic acid) (PAA) and poly(N-acryloyl-glycine) (P1), were graft-copolymerized onto porous cellulose membrane and their protonation behavior in aqueous media was studied by potentiometric techniques. Comparison with the corresponding free polymers in solution showed the same basicity constants during the protonation of ionized carboxyl groups, and the large potentiometric hysteresis loops observed for the grafts were indicative of specific interactions with the cellulose substrate. This was confirmed by FT-IR spectroscopic analysis at low pH. The polymeric membrane system, containing immobilized glucose oxidase, was synthesized for the purpose of insulin delivery in response to glucose concentration. The porosity of the membrane was controlled by the charge-state conformations of the grafted chains. The formation of gluconic acid in the presence of glucose caused a drop in pH which led to neutralization of the negatively charged carboxyl groups. The decrease in electrostatic repulsion caused the extended macromolecular chain to assume a coil-like form and opened the membrane pores to insulin
Ascorbic Acid Derivatives in Two Different Fractions of Uremic Toxins
Authors: Gallice P.M. , Monti J.P. , Braguer D.L. , Baz M. , Elsen R.E. , Berland Y.F. , Crevat A.D.
Published: March 2018

The middle-molecular-weight uremic toxins which accumulate in uremic plasma seem to be associated with various uremic disorders such as uremic neuropathy and defects in the sodium pump. By a multi-step chromatographic method, two fractions of these toxins were isolated and studied because one inhibits microtubule formation in vitro (fraction 2-5), and the other impairs the sodium pump in living erythrocytes (fraction 2-3). An additional chromatographic method allows the separation of these fractions and isolation of two components: fractions 2-3-V and 2-5-III. Analyses by UV and 1H NMR spectrometry identified these compounds as two different ascorbic acid derivatives. 2-3-V is not yet totally identified and 2-5-III corresponds to ascorbic acid 2-sulfate. These two metabolites exert no toxic effects but they have the same chromatographic behavior as uremic toxins.
Extracorporeal Co2 Removal with Hemodialysis (ECBicCO2R): How to Make up for the Bicarbonate Loss?
Authors: Nolte S.H. , Benfer R.H. , Grau J.
Published: March 2018

Hemodialysis is a powerful tool for extracorporeal CO2 removal, because CO2 can be eliminated both as gas and as bicarbonate with blood flow rates as low as 10-15 mI/kg/min. An unsolved problem remains, however: how to make up for the bicarbonate loss. In an animal model we investigated three methods of realkalinisation: a) indirect alkalinisation with salts of organic anions (acetate, lactate, citrate, pyruvate, fumarate, succinate, malate) b) direct realkalinisation with hydroxyl ions (NaOH) c) direct alkalinisation with TRIS as “CO2-buffer”. a) The decrease of pulmonary CO2 elimination depended on metabolism: acetate and lactate were metabolized at a rate of 1.8-3.5 mmol/min, thus allowing a steady-state elimination of 40-75 mmol CO2/min (25-40% of CO2 production). The other organic acids were not metabolized sufficiently to achieve a measurable reduction of pulmonary CO2 elimination. CO2 removal was quantitatively the same as during routine acetate hemodialysis and could not be increased using other organic acids. b) NaOH alone, through theoretically the best substitute for NaHCO3, had serious side effects and led to an increase in pulmonary artery pressure. c) with TRIS at a rate of 5 mmol/min, all metabolic CO2 could be removed for up to seven hours without clinical side effects, but not for longer periods. We conclude that a combination treatment for realkalinisation has to be worked out to compensate for the bicarbonate loss
Aging of Silastic Peritoneal Catheters
Authors: Poisetti P. , Bergonzi G. , Ballocchi S. , Fontana F. , Scarpioni L.
Published: March 2018

Increasing the survival of patients on CAPD is related to the long-term reliability of the peritoneal access. Six silicone Tenckhoff catheters (with strip or diffuse barium sulphate inclusion) removed after 39-69 months because of the appearance of external segment fissures, were analysed by scanning electron microscopy (SEM) and infrared spectroscopy with attenuated total refractance (ATR). The extracorporeal portion of the catheters showed (by ATR) a more prominent oxidation peak on the external than the internal surface; SEM showed marks and cracks on the external surface and exfoliation and flattening of the silastic reticle on the intraluminal surface. No evidence of oxidation was found in the intra-abdominal portion of the catheters but biofilm was found. We suggest that barium sulphate may render the silastic brittle and physiological and environmental long-term factors (such as uv-rays, temperature, sweat and disinfectants) could cause oxidation and loss of physico-chemical properties, with critical aging of the silastic and loss of catheter resistance to mechanical injury.
Static and Dynamic Stresses during Valve Closure of a Bileaflet Mechanical Heart Valve Prosthesis
Authors: Chiang T.H. , Lam H. , Quijano R. , Donham R. , Gilliam P. , Heinz L.A.
Published: March 2018

The effect of contact geometry and component compliance on the magnitude, distribution, and state of various types of stresses on a bileaflet mechanical heart valve prosthesis during valve closure was analyzed using an Edwards-Duromedics™ mitral valve as example. Static and dynamic stresses developing on both the leaflet and pivot ball during valve closure were modeled using finite element analysis (FEA). Uniform contact between the leaflet and housing as well as between the pivot ball and pivot slot can significantly reduce both static and dynamic stresses around the contact area. The level of the dynamic flexural stresses can be an order of magnitude higher than that of the static stresses. When both the radial and axial compliance of the housing are taken into consideration, peak dynamic stress was more than 40% less than that generated through the impact between a moving leaflet and a non-compliant rigid housing.
Heparin-Coated Left Heart Bypass: Renal Function and Hormonal Response
Authors: Weiss B.M. , Von Segesser L.K. , Vetter W. , Gautschi K. , Pasch T.
Published: March 2018

The effect of partial (50 mI/min/kg) left heart bypass (LHBP) on renal function, plasma renin activity (PRA), aldosterone, arginine vasopressin and atrial natriuretic peptide (ANP) response was studied in ten anesthetized, open-chested mongrel dogs (weight 23-50 kg) over a period of 6 h. Standard equipment with systemic heparinization (control), initially 300 IU/kg, was employed in five dogs, and heparin-coated equipment without additional heparin in the other five (heparin coated). Urine was continuously collected through a transurethral catheter. Urine samples and pulmonary artery blood samples for hormonal assays were taken at preset intervals before and during LHBP. The results in each group were summarized as median (25th-75th) and compared using the Mann-Whitney U test. In the control group higher blood loss required higher volume substitution. Urine output was maintained in heparin coated and slightly decreased at 3-4 h in control LHBP. Creatinine clearance at 3-5 h and free-water clearance at 3-6 h were significantly higher with heparin-coated LHBP. PRA, aldosterone and vasopressin peaked at 1-2 h of LHBP similarly in both groups, not exceeding the values before perfusion. PRA and aldosterone response was sustained during 6 h and the percentage changes corrected for hemodilution indicated a stronger response with standard equipment. Vasopressin concentrations were slightly but significantly higher in the control group at 1 and 6 h of perfusion. Corrected for hemodilution, vasopressin percentage changes were not different in the two groups. ANP, despite atrial unloading, rose similarly in both groups. There was a tendency to poorly sustained ANP response (control > heparin-coated) after 6 h of perfusion. In conclusion, preserved renal function and attenuated hormonal response during canine partial LHBP are results of better hemostasis and circulatory integrity of perfusion without systemic heparinization.
Improved On-Line Thoracic Duct Drainage for Lymphocytapheresis
Authors: Sato T. , Koga N. , Nagano T. , Ohteki H. , Masuda T. , Agishi T.
Published: March 2018

Lymphocytapheresis using thoracic duct drainage (TDD) is a recognized technique of extracorporeal immunomodulation for various autoimmune diseases such as rheumatoid arthritis (RA), and its clinical benefit has been reported and generally accepted. Lymphocytapheresis using TDD is very selective for removing lymphocytes (especially helper T-cells) but raises some problems such as hypoproteinemia due to the massive removal of lymph, and difficulties in repeated treatment. Along with the development of a new polyester fiber filter, we have developed a simple and effective method of lymphocytapheresis for wide adoption for these techniques. We performed lymphocytapheresis using TDD in patients with RA and previously reported its clinical efficacy indicated by the significantly lower number of peripheral lymphocytes and T4/T8 ratio. We present here our newly-developed on-line system designed to prevent hypoproteinemia. Furthermore we report on the advantages with a new subcutaneous vascular access device set up to manage the problems of repeated treatments. A small reservoir for keeping the thoracic duct open and returning lymph to the patient permitted sufficient lymph drainage and removal of lymphocytes and the clinical application of TDD is discussed.
Physicochemical and Pharmacological Comparison of Pyridoxylated Hemoglobin Bound to Polyoxyethylene or Polymerized by Glutaraldehyde
Authors: Menu P. , Mouelle P. , Clerc Y. , Labrude P. , Vigneron C.
Published: March 2018

Two modified hemoglobin solutions were assessed using the same physico-chemical and pharmacological techniques. The first was prepared by covalent binding of monomethoxypolyoxyethylene (MPOE) 1.9 kDa to pyridoxylated hemoglobin (PLP-Hb). The resulting conjugate had a molecular size of 100 kDa (MPOE-PLP-Hb). The solution was cleared of non-fixed MPOE through ion exchange chromatography on Spherodex, thus bringing viscosity and oncotic pressure back to physiological values. The second was prepared by limited polymerization of pyridoxylated hemoglobin with glutaraldehyde (POLY-PLP-Hb). Tangential flow ultrafiltration achieved a satisfactory polymer/oligomer return. Quality controls showed no difference between the solutions.

Total isovolemic exsanguinotransfusions in the rat did not help differentiate the two solutions. Hemorrhagic shock (80% of blood volume, rat) gave definitive survival for 8 of the 14 animals tested with MPOE-PLP-Hb (57%) but only 3 of the 8 animals tested with POLY-PLP-Hb (38%). None of the chemical approaches to reduce hemoglobin loss proved any more efficient than another, with the evaluation techniques employed.
Granulocyte Elastase, β-Thromboglobulin, and C3D during Acetate or Bicarbonate Hemodialysis with Hemophan® Compared to a Cellulose Acetate Membrane
Authors: Stegmayr B.G. , Esbensen K. , Gutierrez A. , Lundberg L. , Nielsen B. , Stroemsaeter C-E. , Wehle B.
Published: March 2018

Twenty-two patients were dialysed in a cross-over design using Hemophan® or cellulose acetate membranes. The dialysate buffer was acetate (n = 12) or bicarbonate (n = 10). Blood was sampled at 0, 15, 60 and 180 min and mean values were adjusted for changes in total protein in each sample. At 15 min during dialysis a decrease in leukocytes and platelets occurred with both membranes, irrespective of the buffer (Wilcoxon, p < 0.006). During dialysis, increases were found in granulocyte elastase inhibitor complex (E-α1-PI), β-thromboglobulin and C3d. β2-microgrobulin was not significantly changed in blood after dialysis with Hemophan® or cellulose acetate membranes with bicarbonate buffer. Side effects were more pronounced at 180 min during dialysis with bicarbonate in patients using cellulose acetate than with Hemophan® (p = 0.021, n = 8). Hemophan® seemed to be more favourable than cellulose acetate membranes in regard to leukopenia and E- α1-PI. The dialysate buffer may also alter membrane biocompatibility.
Extracorporeal Lung Assist with Heparin-Coated Systems
Authors: Rossaint R. , Slama K. , Lewandowski K. , Streich R. , Henin P. , Hopfe T. , Barth H. , Nienhaus M. , Weidemann H. , Lemmens P. , Fuchs J. , Falke K.J.
Published: March 2018

Extracorporeal lung assist (ELA) has been recommended for the treatment of ARDS if conventional therapy fails. However, the need for nearly complete anticoagulation is a major risk factor for hemorrhagic complications. We describe our experience with 13 ARDS patients treated with ELA using heparin-coated systems (Carmeda). Maintaining partial thromboplastin time and activated clotting time within or close to the normal range, even major surgery (20 thoracotomies and 2 laparotomies) could be performed without undue bleeding complications related to anticoagulation during extracorporeal support. Eight of the 13 patients survived. The use of heparin-coated systems allows prolonged ELA with nearly physiological coagulation function, permitting major surgical intervention. It enhances the safety margin of extracorporeal gas exchange and may ultimately extend its indications.
Compact Mock Loops of the Systemic and Pulmonary Circulation for Blood Pump Testing
Authors: Knierbein B. , Reul H. , Eilers R. , Lange M. , Kaufmann R. , Rau G.
Published: March 2018

Mock loops are an important tool for in vitro investigations of artificial blood pumps. The simple windkessel, throttle, and atrium principle was used for the mock loop design presented. The components of the systemic and the pulmonary mock loop were designed according to calculated numerical simulation parameters. The loops offer a compact design and simple handling. For simulating biventricular assist or total artificial heart (TAH), both loops can be coupled correspondingly. The numerical simulation and the first results with the loops show very good similarity to physiological data of systemic and pulmonary circulation. The measurements of pump characteristics are significant for quantitative comparison of different pump sizes and types, or driving systems.
Leukotriene Release from Neutrophils of Patients on Hemodialysis with Cellulose Membranes
Authors: Jörres A. , Jörres D. , Gahl G.M. , Schulz E. , Mahiout A.
Published: March 2018

The role of cytokines in patients with chronic renal failure is currently under investigation. We therefore studied the release of leukotriene B4 (LTB4) from polymorphonuclear leukocytes (PMN) in stable dialysis patients treated with two different cellulose membranes, Cuprophan and Hemophan®, a modified cellulose with less complement activation. Six patients were treated for four weeks with Cuprophan then switched to Hemophan® for another four weeks. Before and after the last treatment of each period, PMN were separated from 20 ml heparinized blood by FICOLL density gradient centrifugation. Portions of 5x106 PMN were resuspended in Hanks' buffer and stimulated for 5 minutes with calcium ionophore A23187 (5 /μg/ml). LTB4 in cell supernatants was determined by specific radioimmunoassay. PMN from dialysis patients before HD released significantly (p<0.01) more LTB4 than healthy donors. No significant difference between pre- and post-dialysis values was observed with Cuprophan or Hemophan® dialyzers. Our data suggest that the acute effects of blood membrane interaction with either complement activating or non-activating dialyzers do not lead to changes in post-dialysis leukotriene metabolism, but leukotriene production is enhanced chronically in dialysis patients.
Progress in Veno-Venous Long-Term Bypass Techniques for the Treatment of Ards
Authors: Knoch M. , Köllen B. , Dietrich G. , Müller E. , Mottaghy K. , Lennartz H.
Published: March 2018

Extracorporeal CO2 removal combined with low-frequency positive pressure ventilation (ECCO2-R LFPPV) is a new therapeutic approach in treatment of ARDS. The main problem during long-term extracorporeal support is anticoagulation and related bleeding problems. We conducted a prospective, randomized and controlled clinical trial in 18 patients to compare the effect of the non-heparin-coated (Scimed = group 1) with the heparin-coated (Carmeda = group 2) extracorporeal circuit on clinical course and complication rate. In group 2 the daily blood loss, the amount of substituted red cells and the i.v. heparin dose were significantly lower than in group 1. Bleeding complications were less and more patients survived in group 2. The disadvantage of the hollow fiber oxygenators in the heparin-coated system was plasma leakage, which was more frequent in patients with pancreatitis and hyperbilirubinemia.
Biochemical and Immunological Studies in Calves Living over Three Months with a Total Artificial Heart
Authors: Cídl K. , Dostál M. , Vašků JAN , Nečas J. , Dobša'k P.
Published: March 2018

Changes in serum proteins, enzymes and isoenzymes of lactate dehydrogenase (LDH) were compared in long-term surviving calves with a total artificial heart without influencing their central venous pressure (CVP) and calves in which CVP was lowered by antihypertensive drugs administered from day 60 to the end of the experiment. Antihypertensive drugs helped keep CVP within physiological levels for longer and aided liver function as well as evidenced by the different values for the parameters studied in the two groups.
Membrane Bioreactors as Hybrid Artificial Pancreas: Experimental Evaluation
Authors: Lombardi C.P. , Urso A. , Catapano G. , Careddu G. , Ghirlanda G. , Ceriati F. , Brisinda G. , Bellantone R. , Doglietto G.B. , Crucitti F.
Published: March 2018

Results of cultured islet transplantation in the management of insulin-dependent diabetes are still unsatisfactory. The main problem preventing success is the swift and resolute host immune rejection. To obviate this we designed and experimented a model of bioartificial pancreas, made of polymeric hollow fibers, put into the blood circulation as an artero-venous bypass to immunoisolate endocrine tissue from leucocytes and immunoglobulins. We tested four different membrane bioreactors (BR1-4). BR1 and 2 had seven hollow fibers, the others more than 6,000 smaller fibers. In BR4 a connecting tube with a high-permeability membrane was inserted between the islet compartment and the bioreactor outlet to improve the ultrafiltration flow. In vitro, the islets inside the bioreactor perfused with glucose solutions (300 mg%) showed a rapid, high insulin secretory response, related to the glucose stimulation. The use of the outside connection allowed a twofold increase of insulin production.
Failure of Blood Pressure to Increase following Erythropoietin Therapy in the Renoprival Status
Authors: De Santo N.G. , Manzo M. , Raiola P. , Lanzetti N. , Capasso G. , Ficociello R. , Anastasio P. , Esposito R.
Published: March 2018

Two anephric patients in the course of one year erythropoietin therapy improved their anemic status without changes in Mean Arterial Blood Pressure. The discordant time course behaviour of hematocrit and blood pressure points to the importance of residual renal tissue for blood pressure to develop during erythropoietin therapy in the renoprival status.
Changes in Coagulation Factors by Passage through a Dextran Sulfate Cellulose Column during Low-Density Lipoprotein Apheresis
Authors: Kojima S. , Harada-Shiba M. , Toyota Y. , Kimura G. , Tsushima M. , Kuramochi M. , Sakata T. , Uchida K. , Yamamoto A. , Omae T.
Published: March 2018

To determine the extent of adsorption of coagulation factors by a dextran sulfate cellulose column used for selective removal of low-density lipoprotein (LDL), various coagulation factors were measured before and after application to the column during LDL apheresis. The column almost completely adsorbed many coagulation factors. Although the bradykinin concentration was markedly increased by passing the plasma through the column, this increment was suppressed by nafamostat mesilate which inhibits the initial contact phase of the intrinsic coagulation pathway. The von Willebrand factor, which forms a complex with factor VIII in plasma, is reduced in apheresis with nafamostat mesilate to the same extent as in apheresis without nafamostat mesilate. Thus, coagulation factors seem to be adsorbed by different mechanisms which include activation of the initial contact phase by the negative charges of dextran sulfate and concomitant adsorption with the phospholipid portion of lipoproteins containing apolipoprotein B or with von Willebrand factor.
Novel Quantitative Methods for the Determination of Biomaterial Cytotoxicity
Authors: Smith M.D. , Barbenel J.C. , Courtney J.M. , Grant M.H.
Published: March 2018

Two novel methods for the determination of biomaterial cytotoxicity using cell culture are presented. The methods combine a standardized protocol for producing extracts from medical devices with either the established MTT assay or a new fluorimetric assay. The suitability of both methods for evaluating the toxicity of candidate materials was demonstrated by resolution of the differences in the toxic effects of serial dilutions of a PVC extract on BHK21 and HT1080 cells. The tests yield highly reproducible, quantitative results and can be applied to materials in the usual physical forms applicable to artificial organs.
Enhanced O2 Transportation During Cardiopulmonary Bypass in Piglets by the use of Inositol Hexaphosphate Loaded Red Blood Cells
Authors: Deleuze P.H. , Bailleul C. , Shiiya N. , Bourget G. , Moire T. , Kotoh K. , Leandri J. , Teisseire B.P. , Ropars C. , Loisance D.Y.
Published: March 2018

A continuous lysing and resealing of erythrocytes permitted internalization of inositol hexaphosphate (IHP), a strong allosteric effector of Hb, leading to significant rightward shifts of the HbO2 dissociation curve. Twelve piglets were put on cardiopulmonary bypass (CPB) with the heart beating, cooled to 25° C then rewarmed to 37° C before weaning off CPB. AoP, LV pressure, PAP, and cardiac output (CO) were monitored. Blood samples were taken before CPB, at 25° C, at 30° C, at 37° C and after CPB for assessment of blood gases, arterio-venous difference in O2 content, lactates, P50 (partial pressure of O2 at 50% Hb saturation), and ionogram. Control group I included five pigs where the CPB circuit was primed with Ringer's lactate solution and porcine blood. In group II (n=5), priming was done with Ringer's lactate solution and IHP loaded erythrocytes. P50 was significantly higher during CPB than before surgery in group II (20%), but not in group I (1%). There was a significant increase in VO2 in group II (6.02 ml/min) compared to group I (4.03 ml/min) (p < 0.05) after CPB. Hemodynamics improved after CPB in group II (mean AoP 42 mmHg and syst LVP 70 mmHg) compared to group I (AoP 25 mmHg and syst LVP 22.5 mmHg). These preliminary results show that O2 transportation at the end of CPB is enhanced and myocardial function is improved in piglets with the use of IHP erythrocytes.
Adsorption Profile of Commercially Available Adsorbents: An in Vitro Evaluation
Authors: Ikonomov V. , Samtleben W. , Schmidt B. , Blumenstein M. , Gurland H.J.
Published: March 2018

Adsorbents from four commercially available devices, Protein A-Sepharose (Immunosorba Protein A-62,5; Excorim KB, Lund Sweden), Tryptophan-PVA (Immusorba TR-350; Asahi Medical Co., Tokyo, Japan), Phenylalanine-PVA (Immusorba PH-350; Asahi Medical Co., Tokyo, Japan), and Dextran sulfate (Liposorber LA-15; Kanegafuchi Chemical Co. Ltd, Osaka, Japan) were tested under optimal in vitro conditions to determine their adsorption capability for several plasma constituents which are usually the target of plasma therapy. The parameters of interest were: double stranded DNA-antibodies (anti-dsDNA), antiglomerular basement membrane antibodies (anti-GBM), antiacetylcholin receptor antibodies (AChRAb), circulating immune complexes (CIC), rheumatoid factor (RF), IgA, IgG, IgM, IgE, C3c, C4, LDL-cholesterol, total cholesterol, erythropoietin (EPO) and β2-microglobulin (β2M). The IgG auto antibodies, CIC and RF can be removed by Protein A-Sepharose, Try-PVA and Phe-PVA. IgG is best adsorbed by Protein A-Sepharose, while IgE can be removed effciently by Try-PVA. Dextran sulfate is without doubt the best adsorbent for LDL-cholesterol. All four adsorbents bind also complement components C3c and C4. No significant adsorption was found for EPO and β2M. The four devices exhibit a quite different adsorption profile which can be used as a guide for the optimal selection of an adsorption column in clinical apheresis.
An Equation for Calculating Postdialysis Plasma Sodium
Authors: Lopot F. , Bláha J. , Válek A.
Published: March 2018

Well defined dry weight is a must for adequate UF control during haemodialysis (HD). However, interdialytic weight gain (ΔBW) must not be excessive. ΔBW is closely related to interdialytic thirst which in turn is strongly influenced by postdialysis plasma sodium (CPNapost), but little is known about the desired CpNapost. The points below serve as a basis for establishing this value.

a) Thirst is mediated by osmoreceptors.

b) A strong correlation has been found between ΔBW and intradialytic increase in plasma sodium but no such correlation exists with the interdialytic increase in plasma urea. This indicates that fluid intake between dialyses depends solely on electrolytes.

c) Pre-dialysis plasma sodium in an individual is stable, indicating that the patient is at his “set value” of electrolyte osmolality.

d) Half of the potassium removed during HD comes from the extra- and half from the intracellular space.

Assuming that it is desirable not to disturb a patient's predialysis osmotic steady state, it can be calculated that the desired CPNapost should be higher than the predialysis value by half of the intradialytic plasma potassium drop, i.e., approx. CPNapost = CPNapre + 1 to 2 mmol/l.
Blood Coagulation, Fibrinolytic and Inhibitory Profiles in Renal Transplant Recipients: Comparison of Cyclosporine and Azathioprine
Authors: Vaziri N.D. , Ismail M. , Martin D.C. , Gonzales E.
Published: March 2018

Renal transplant recipients treated with cyclosporine (CS) have been reported to be at increased risk of thrombotic complications. The present study was intended to examine the blood coagulation, fibrinolytic, and inhibitory systems in such patients. Eight transplant recipients on maintenance immunosuppression with CS and prednisone were studied. Five transplant recipients maintained on azathioprine (AZA) and prednisone and 32 normal volunteers served as controls. Plasma antigen concentrations and/or activities of various proteins in the above pathways were measured. Both the CS and AZA groups exhibited significant elevations of factor IX activity, von Willebrand factor (vWF), D-dimer, protein C and tissue type plasminogen activator (t-PA) levels when compared with the normal controls. In addition, CS group showed a significant elevation of α2-macroglobulin activity and AZA group showed a significant reduction in factor XII activity when compared with the normal controls. Comparison of data from CS and AZA groups revealed higher factor XII activity and vWF concentration in the former group. In conclusion, transplant recipients treated with long-term cyclosporine and prednisone exhibited significant elevation of plasma vWF, D-dimer and protein C concentrations. In addition, both CS and AZA-treated transplant recipients showed increased plasma concentrations of D-dimer and t-PA. The latter observations suggest in vivo thrombin generation, fibrin formation and degradation.
Transcutaneous Transmission of Digital Data and Energy in a Cochlear Prosthesis System
Authors: Zierhofer M.C. , Hochmair E.S.
Published: March 2018

This paper describes the inductive power and data link employed in the CAP Cochlear Prosthesis System (CAP stands for Combined Analog and Pulsative Stimulation Strategy). The inductive link consisting of a parallel-tuned receiver resonant circuit weakly coupled to a series-tuned transmitter resonant circuit, is driven by a self-oscillating class-E-tuned power amplifier. The class-E concept allows coupling-insensitive high-efficency transcutaneous transmission of power. In the CAP implant, variations of the coil distance within a range of 0 to 9 mm result in changes of the implant supply voltage which are lower than 10%. Within this coil distance range, the mean overall efficiency is 49%. In view of the excellent switching properties of the class-E tuned power oscillator, a practical scheme for data transmission is ASK (Amplitude Shift Keying). To ensure constant energy flow and easy synchronization of the bitstream in the implant, a self-clocking bit format is employed.