bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and analysis of coupling methods for modular endoprosthetic systems as an alternative to the conical coupling
Authors: Polmans R.P.J. , Grootenboer H.J. , Koops H. Schraffordt , Veth R.P.H. , van Horn J.R. , Verkerke G.J.
Published: March 2018

Modular endoprostheses are often used in bone tumor management. However, the conical coupling that connects the various modules has several shortcomings. As an alternative, four new couplings have been developed. To find out if they have sufficient strength and show no movement during loading, each coupling was analysed using the finite element method. Bolt force and friction coefficient was varied to examine their influence.

From the analysis it was concluded that coupling B, a dovetail coupling, meets all requirements and is the best alternative to the conical coupling. Sensitivity to bolt force and friction coefficient is very limited.
Daily Dialysis Kt/V and Flexible Schedules: Is it Possible to Control Efficiency, When and How?
Authors: Piccoli G.B. , Calderini M. , Bechis F. , Pacitti A. , Vischi M. , Iacuzzo C. , Mezza E. , Gai M. , Anania P. , Iadarola A.M. , Buniva C. , Jeantet A. , Segoloni G.
Published: March 2018

Background

Daily hemodialysis is a promising treatment schedule but uniform criteria for defining efficiency are lacking.

Methods

On our daily dialysis (DD) schedule, duration is flexible (2–3 hours, patients are free to add up to 30min/session), Qb 250–350 mL/min; dialyser 1.6–1.8 m2. Study was performed on 12 pts on DD for ≥2 months, with ≥4 Kt/V on subsequent days, tested in the same laboratory. Goal: To evaluate variability and identify a simple method for weekly calculation, Kt/V was assessed for 133 sessions.

Results

On flexible DD, variability of Kt/V-session is high (relative error 4.9%-22%). On flexible schedules, within the time range chosen (2–3 hours) variability of average hourly Kt/V is lower (standard deviation: min (0.014; max (0.052 hour, relative error 4.9%-10%) allowing calculation of weekly Kt/V (averaging 3 sessions: relative error <6%) suitable for clinical practice.

Conclusions

Flexible schedules, allowing patients to increase treatment time, are an interesting clinical option, but a challenge for Kt/V assessment.
A Controlled Study of Sorbent Suspension Dialysis in Chronic Liver Disease and Hepatic Encephalopathy
Authors: Kramer L. , Gendo A. , Madl C. , Mullen K.D. , Kaminski-Russ K. , Sunder-Plassmann G. , Schaffer A. , Bauer E. , Roth E. , Ferenci P.
Published: March 2018

To investigate the role of extracorporeal detoxification in cirrhotic patients with advanced hepatic encephalopathy not responding to medical treatment, 20 patients were randomized to receive six hours of additional sorbent dialysis or ongoing standardized medical treatment. Following treatment, the clinical stage of encephalopathy remained unchanged in both groups. Abnormal sensory evoked potentials improved following sorbent dialysis (N70 latency, 128 ms before versus 110 ms after treatment, P<0,05; cervico-cranial transmission, 7.7 ms versus 6.8 ms, P<0.01) indicating improvement in important aspects of cerebral function. In contrast, brain function remained unchanged following medical treatment (N70 latency, 114 ms versus 113 ms; cervico-cranial transmission, 7.7 ms versus 7.2 ms, P=NS, respectively). Serum benzodiazepine levels decreased significantly after sorbent dialysis but not after medical treatment. Biocompatibility of sorbent dialysis was limited and clinical complications occurred in a proportion of patients. In conclusion, a six-hour treatment with sorbent suspension dialysis did not ameliorate the clinical stage of HE but improved neurophysiologic function in cirrhotic patients who had not responded to conventional medical treatment.
Arterial Compliance is an Independent Factor Predicting Acute Hemodynamic Performance of Intra-aortic Balloon Counterpulsation
Authors: Papaioannou T.G. , Lekakis J.P. , Dagre A.G. , Stamatelopoulos K.S. , Terrovitis J. , Gialafos E.J. , Kanakakis J. , Nanas J. , Stamatelopoulos S.F. , Moulopoulos S.
Published: March 2018

Data concerning the effect of arterial compliance (AC) on hemodynamics during intra-aortic balloon counterpulsation (IABC) are lacking. This study examines the effect of AC on acute hemodynamics induced by IABC in 15 patients with post-infarction cardiogenic shock. AC was estimated by aortic pulse wave analysis using the reflection time index (RTI). Measurements were obtained once per day during IABC. The % reduction in systolic aortic pressure (ΔSAP), end-diastolic aortic pressure (ΔEDAP) and the peak aortic diastolic augmentation (PADA) were used as performance indices of IABC; 107 sets of measurements were obtained. Multivariate analysis indicated an independent association of each IABC performance index with AC (p<0.05). A high AC group (RTI≤20.6%, n=40) and a low AC group (RTI>20.6%, n=67) were obtained. ΔSAP, ΔEDAP and PADA were significantly higher in the low AC group by almost 75%, 54.6% and 11,3% (p<0.03), while arterial blood pressure did not significantly differ. Arterial compliance is an independent factor affecting hemodynamics during IABC. RTI values higher than 20.6% may predict a better acute hemodynamic response to IABC.
Ash Split Cath® in Geriatric Dialyzed Patients
Authors: Conz P.A. , Catalano C. , Rizzioli E. , Normanno M. , Fabbian F. , Preciso G.
Published: March 2018

Vascular access is the essential step in performing hemodialysis in uremic patients. In the absence of a permanent and utilizable native arterio-venous fistula, the use of a tunnelled catheter makes dialysis therapy possible. The Ash Split Cath, a recently introduced chronic hemodialysis catheter, was inserted in five patients (7.1 % of our prevalent dialysis population) because of repeated venous thrombosis in three patients and a poor venous tree in two. The mean age of patients was 78 years ± 7. The average blood flow rate was 250 ± 50 ml/minute and the mean venous pressure 140mm Hg ± 35. Recirculation determined by low flux technique was less than 2 %. KT/V calculated 3 months after the catheter placement was 1.2 ± 0.02. During the follow-up we did not document any infection of the exit site or related to the catheter.

This device is simple to place, gives adequate dialysis treatment and is useful in geriatric dialyzed patients in whom the arterio-venous fistula can no longer be used.
Pressure Drops in Cannulas for Hemodialysis
Authors: Polaschegg H.D.
Published: March 2018

Pressure drops in cannulas for hemodialysis have been measured in vitro in both flow directions for five different viscosities and up to 600 mL/min flow. Cannula dimensions were 15, 16 and 17 gauge and 15, 20 and 25 mm nominal length. The measurements were taken at room temperature with glycerin solutions as test fluid.

Results

The pressure drops can be described by a second order function but not by the Hagen-Poiseuille law even when corrected for inlet and outlet effects as described by Bernoulli's law. Pressure drops depend on flow direction. Back-eyes and cannula tips have no influence on the pressure drop. Pressure drops and especially flow direction asymmetry are influenced by the hydraulic design of the connection piece between cannula and tubing. The results can be used for prediction of pressure drops in cannulas allowing better use of pressures already measured in the extracorporeal circuit of hemodialysis machines.
Pulsatile Flow and Atherogenesis: Results from in Vivo Studies
Authors: Grigioni M. , Daniele C. , D'Avenio G. , Formigari R. , Bernucci P. , Ballerini L. , Barbaro V.
Published: March 2018

Compliance mismatch between prosthetic vascular replacement (possibly stented) and native artery is considered to be an important factor in implant failure due, e.g., to vascular remodeling, tissutal growth or intimal hyperplasia (IH). From an in vivo study involving altered vascular mechanics (and, consequently, compliance mismatch), carried out using the Moncada model of atherosclerosis development and smooth muscle cell (SMC) proliferation, the hemodynamic assessment was followed by means of real-time multigated ultrasound profilometry, of collared carotid artery using two different models: nonconstrictive and costrictive plastic collars, wrapped around the vessel. The experiments provided the real-time measurement of velocity profiles in vivo and the subsequent estimation of wall shear stresses, locally responsible for the altered hemodynamics.

Endothelium modifications were correlated with local hemodynamic alterations by using statistical regression analysis of the development of intimal hyperplasia and the mechanical stimulus applied to the endothelium by means of the two different manipulation models. Different correlations were found between wall shear rate and IH in the two models, showing the importance of the vascular pulsatility in determining SMC proliferation. This result could be useful in minimizing the negative consequences of clinical interventions such as graft and/or stent implantation.
Optimization and Investigation of a Novel Cardiac Assist Valve with a Purge Flow
Authors: Timmel T. , Goubergrits L. , Affeld K.
Published: March 2018

Clinical applications of cardiac assist systems still suffer from thromboembolic complications due to thrombus formation behind the valve's leaflets. Wherever the flow is stagnant such as in the sinus, a thrombus is likely to form. The valve design in this study avoids stagnation zones behind the leaflets by a purge flow during systole. This purge flow is separated from the valve's main flow by a flow divider directing a part of the main flow into the sinus behind the leaflet. The optimization was performed on a monoleaflet valve because of its simple geometry. Relevant geometric parameters were systematically varied. Thirty-two models were designed and numerically investigated. The models with the best results were preselected and investigated in a computer-controlled valve tester. The washout of a dye filled in the sinus was digitally recorded and quantified. The results show that a sinus purge flow minimizes stagnation areas in the sinus and thus may avoid thrombus formation.
Enhancing Filtration Rates by the use of Blood Flow around the Capillaries of Plasmafilters: An in Vitro Study
Authors: Unger J.K. , Janssen V.R. , Kashefi A. , Haltern C. , Klosterhalfen B. , Fischer Y. , Gressner A.M. , Rossaint R.
Published: March 2018

As the low clearance rate of plasmaseparation limits its use in the treatment of patients suffering from liver failure, sepsis or MOF, we intend to develop strategies for a plasmaseparation unit which increases plasmafiltration rates. Our first question focused on whether commercially available plasmaseparation filters, and in particular their membranes, are suitable for the inversion of blood and plasma compartments. This experimental study was performed using in vitro systems. Commercially available plasmafilters PF2000N (Gambro) and Plasmaflo (Asahi) were compared in both their normal operating mode with blood flow through the capillary lumen, and in the inverse mode. Inverse mode means that blood flows through the outer space of the capillaries while plasma was obtained from the lumen. Heparinised porcine blood (5 I.U./ml) was used in a heated, recirculating in vitro circuit. Our main results were that the normal use of both filter types Plasmaflo and PF2000N enabled maximal blood flows (Qb) of 200 ml/min and filtration rates (Qf) of 25–40 ml/min. Operating the filters in the inverse mode enabled Qb up to 500 ml/min and Qf up to 100 ml/min. Hemolysis, platelet counts and coagulation parameters did not differ significantly regardless of whether the normal or inverse mode was used. The tested plasmafiltration membranes appear to be suitable for use in inverse mode. Although in our experiments, hemocompatibility tests did not indicate severe problems induced by the module geometry, the development of a module specially constructed for blood flow outside of the hollow fibers appears to be necessary in order to minimise shunts and low perfusion areas.
Two-Photon Techniques in Tissue Engineering
Authors: Schade Ronald , Weiß Thomas , Berg Albrecht , Schnabelrauch Matthias , Liefeith Klaus
Published: March 2018

Purpose

NIR radiation in the range of about 800 nm is less absorbed by biological tissues and is suited for triggering photonic effects using femtosecond pulsed Ti: Sa lasers. Especially in the life sciences, two-photon techniques are gaining greater importance. We introduce two laser applications for tissue engineering: the autofluorescent visualization of cells seeded on 3D scaffolds after two-photon excitation; and the manufacturing of 3D-structured hydrogel-like scaffolds by triggering free-radical polymerization processes within polymerizable precursors.

Methods

Primary bovine chondrocytes were cultivated on collagen I/III scaffolds using a flow chamber system coupled with a two-photon laser scanning microscope (2PLSM). During the incubation the cell population was hydrostatically stimulated. The selective visualization of unlabeled cells and scaffolds was achieved by spectral autofluorescence imaging. To gain some insight into scaffold-mediated effects on cell growth and cell differentiation, hydrogel-like scaffolds with well defined 3D structures were generated by two-photon polymerization (2PP) using methacrylated urethane and polyethyleneglycol diacrylate.

Results

We were able to show that spectral autofluorescence imaging provides spatially resolved data for the non-invasive online control of the tissue engineering process as well as the quantification of cell distribution within the scaffold. The fabrication of 3D 2PP scaffolds made from hydrogel-forming monomers and their effect on cell attachment and cell growth were also shown.

Conclusions

Two-photon techniques provide powerful tools for both the non-invasive online visualization of 3D cell-scaffold constructs and the structuring of 3D cultivation environments. The application of these techniques is also suitable for integration into micro-systems technology (e.g. BioMEMS, Cells-on-Chip, Lab-on-a Chip).
Combined Impedance Spectroscopy and Fourier Domain Optical Coherence Tomography to Monitor Cells in Three-Dimensional Structures
Authors: Bagnaninchi Pierre O.
Published: March 2018

Objectives

To assess non-invasively and in real time the three- dimensional organization of cells within porous matrices by combining Fourier Domain Optical Coherence Tomography (FDOCT) and Impedance Spectroscopy (IS).

Materials and Methods

Broadband interferences resulting from the recombination of in-depth light scattering events within the sample and light from a reference arm are measured as a modulation of the spectrum generated by a superluminescent laser diode (λo = 930nm, FWHM 90nm). Fourier transform allows in-depth localization of the scatterers, and the 3D microstructure of the sample is reconstructed by raster scanning. Simultaneously impedance spectroscopy is performed with a dielectric probe connected to an impedance analyzer to gather additional cellular information, and synchronized with FDOCT measurements.

Results

A combined IS-FDOCT system allowing an axial resolution of 5 micrometer in tissues and impedance measurements over the range 20MHz-1GHz has been developed. Alginate matrices have been characterized in terms of microstructure and impedance. Matrices seeded with adipose-derived stem cells have been monitored without the use of labeling agent.

Conclusions

We have developed a multimodality system that will be instrumental to non-invasively monitor changes in total cell volume fraction and infer cell-specific dielectric properties in 3D structure.
Intervertebral Disc Regeneration: Influence of Growth Factors on Differentiation of Human Mesenchymal Stem Cells (hMSC)
Authors: Ehlicke Franziska , Freimark Denise , Heil Birthe , Dorresteijn Adriaan , Czermak Peter
Published: March 2018

Introduction

One common cause of disability in modern society is low back pain. The main reason for this pain is the degeneration of the intervertebral disc (IVD), particularly of the nucleus pulposus (NP). For the early degeneration stage, a cell-based therapy could constitute a minimally invasive method of treatment. Therefore, adequate cells are needed. As the usage of NP cells is limited because of their insufficient amount or vitality, a promising alternative is the application of human mesenchymal stem cells (hMSCs).

Objective

To investigate the potential of various growth factors to induce the differentiation of hMSCs into NP cells and thereby to obtain an alternative cell source for the treatment of IVD degeneration.

Methods

hMSC-TERT were cultivated three-dimensionally in a hydrogel for 21 days to form NP cells. Cell survival and proliferation were determined using SybrGreen/propidium iodide double staining and the WST-test. To investigate the ability of several growth factors to differentiate hMSCs into NP cells, fluorescence immunostaining of NP-specific marker proteins (e.g., chondroadherin (CHAD) and the recently discovered cytokeratin 19) were performed.

Results

Following the procedure described above, cells are able to maintain their viability and proliferation capacity throughout the cultivation time. By using a previously established immunofluorescence protocol, we were able to indicate the ability of three different growth factors for differentiating hMSCs into NP-like cells.

Conclusion

The expression of several marker proteins in all differentiation experiments indicates the ability of IGF-1, FGF-2 and PDGF-BB to differentiate hMSCs into NP-like cells apart from the usually applied TGF-β3. Furthermore, our findings preclude the application of Cytokeratin 19 as a specific marker protein for NP cells. Further experiments have to be done to find real specific NP marker proteins to indisputably verify the differentiation of hMSCs into NP cells. If so, application of these three growth factors would possibly be an option to obtain sufficient NP cells for minimally invasive IVD regeneration.
Effects of Low Concentrated BMP-7 Administered by co-Cultivation or Plasmid Transfection on Human Osteoarthritic Chondrocytes
Authors: Gavenis Karsten , Schneider Ulrich , Wallich Reinhard , Mueller-Rath Ralf , Schmidt-Rohlfing Bernhard , Andereya Stefan
Published: March 2018

Introduction

While BMP-7 has proven to be one of the most potent growth factors in cartilage tissue engineering, protein concentration and route of administration remain a matter of debate. Here we investigated the effects of a low concentration of BMP-7 on human osteoarthritic chondrocytes administered by protein co-cultivation and plasmid transfection.

Methods

Freshly released (P0) or in vitro propagated chondrocytes (P2) were cultivated in a collagen type-I gel for 3 weeks in vitro or in nude mice. Seeded chondrocytes were treated with 50 ng/mL BMP-7 directly added to the medium or were subject to transient BMP-7 plasmid transfection prior to gel cultivation. Untreated specimens served as a control. After recovery, samples were investigated by histological and immunohistochemical staining and real-time PCR.

Results

In vitro, collagen type-II protein production was enhanced, and it was stored mainly pericellularly. Collagen type-II and aggrecan gene expression were enhanced in both treatment groups. After nude mouse cultivation, col-II protein production was further enhanced, but specimens of the BMP-7 transfection group revealed a clustering of col-II positive cells. Gene expression was strongly up-regulated, chondrocyte number was increased and the differentiated phenotype prevailed. In general, freshly released chondrocytes (P0) proved to be superior to chondrocytes pre-amplified in vitro (P2).

Conclusions

Both BMP-7 co-cultivation and plasmid transfection of human osteoarthritic chondrocytes led to improved cartilage repair tissue. Nevertheless, the col-II distribution following BMP-7 co-cultivation was homogeneous, while samples produced by transient transfection revealed a col-II clustering.
A Three-Dimensional Traction/Torsion Bioreactor System for Tissue Engineering
Authors: Scaglione Silvia , Zerega Barbara , Badano Roberto , Benatti Umberto , Fato Marco , Quarto Rodolfo
Published: March 2018

Purpose

The aim of this study was to design, develop and validate a simple, compact bioreactor system for tissue engineering. The resulting bioreactor was designed to achieve ease-of-use and low costs for automated cell-culturing procedures onto three-dimensional scaffolds under controlled torsion/traction regimes.

Methods

Highly porous poly-caprolactone-based scaffolds were used as substrates colonized by fibroblast cells (3T3 cell line). Constructs were placed within the cylindrical culture chamber, clumped at the ends and exposed to controlled sequences of torsional stimuli (forward/back-forward sequential cycles of 100° from neutral position at a rate of 600°/min) through a stepper-motor; working settings were defined via PC by an easy user-interface. Cell adhesion, morphology, cytoskeletal fiber orientation and gene expression of extracellular matrix proteins (collagen type I, tenascin C, collagen type III) were evaluated after three days of torsional stimulation in the bioreactor system.

Results and Conclusions

The 3D bioreactor system was validated in terms of sterility, experimental reproducibility and flexibility. Cells adhered well onto the polymeric scaffolds. Collagen type I, tenascin C and collagen type III gene expression were significantly up-regulated when cells were cultured under torsion in the bioreactor for three days. In conclusion, we have developed a simple, efficient and versatile 3D cell-culture system to engineer ligament grafts. This system can be used either as a model to investigate mechanisms of tissue development or as a graft manufacturing system for possible clinical use in the field of regenerative medicine.
Perfusion Enhances Solute Transfer into the Shell of Hollow Fiber Membrane Bioreactors for Bone Tissue Engineering
Authors: De Napoli Ilaria Ester , Catapano Gerardo
Published: March 2018

Preparation of tissue engineered (TE) 3D constructs to repair large bone defects is limited by the difficult supply of nutrients and oxygen to cells in the innermost regions of constructs cultured in bioreactors. Poor oxygenation negatively affects cell viability and function. Bioreactor design optimization may help relieve these limitations. Bioreactors in which cells are cultured outside bundles of hollow fiber membranes (HFMBs) are structurally similar to natural bone. HFMB operation in pure diffusion has been reported to suffice for fibroblasts, but is deemed insufficient for bone cells. In this paper, the effect of perfusion flows in the cell compartment on solute transfer was investigated in HFMBs differing in design and operating conditions. HFMBs were designed and operated using values of non-dimensional groups that ensured solutes transfer towards the cell compartment mainly by diffusion; in the presence of low to high Starling flows; in the presence of pulsatile radial flows obtained by periodically stopping the solution flow leaving the bioreactor using a pinch valve. Distribution of matter in cell-free HFMBs was evaluated with tracer experiments in an optimized apparatus. Effectiveness of solute transfer to cell compartment was assessed based on the bioreactor response in terms of the shell volume actively involved in mass transfer (VMTA) according to transport models developed specifically for the purpose. VMTA increased with increasing Starling flows. In the pulsatile radial flow mode, tracer concentration in the shell increased 3 times faster than at high Starling flows. This suggests that controlled perfusion flows in HFMBs might enable the engineering of large TE bone constructs.
The modified polymethyl methacrylate-silicone keratoprosthesis in rabbit model
Authors: Sun Heng , Hu Zhu-lin
Published: March 2018

Purpose:

To evaluate the safety and effectiveness of a modified polymethyl methacrylate-silicone keratoprosthesis and its operation method in alkali-burned rabbit model.

Methods and materials:

The polymethyl methacrylate-silicone keratoprostheses were implanted into seven alkali-burned rabbit corneas by a special operation method using autologous graft as the keratoprosthesis (Kpro) carrier. The long-term postoperative outcomes were evaluated.

Results:

During a postoperative study period of 16 months, except for one Kpro extruded at 3 months, all Kpros were in good position and were kept transparent without Kpro extrusion, keratolysis, infection, endophthalmitis, or retinal detachment. The postoperative complications included elevated intraocular pressure in two cases and temporary retroprosthetic membrane formation in two cases.

Conclusion:

The modified polymethyl methacrylate-silicone Kpro and its operation method is a relatively safe and effective choice for alkali-burned rabbit eyes. Elevated intraocular pressure is the main complication needing to be resolved.
Sterilization of Therapeutic Immunoadsorbents with Aqueous Propylene Oxide Solution
Authors: Sato H. , Kidaka T. , Hori M.
Published: March 2018

Propylene oxide (PO), in the form of its aqueous solution, was evaluated as a chemical sterilant for therapeutic immunoadsorbent to be used in on-line plasmapheresis. Generally, PO is characterized as less toxic and less antimicrobial than ethylene oxide. PO was significant sporicidal to B. subtilis at 25°C and 10β spores/ml were killed with 1% (V/V) PO solution after storage for 3 weeks when 75% to 80% of PO decomposed; the death-rate conformed to the kinetics of a first-order reaction although PO decomposed rapidly. Thus an apparent D values were estimated to be 13 to 16 days with 0.5% PO solution and 5 to 7 days with 1% PO.

An immunoadsorbent consisting of Sepharose 4B immobilizing anti-human IgE antibody was used to study the effect of PO on adsorption characteristics. PO affected the IgE removal of the immunoadsorbents depending on its concentration ranging from 0% to 4%. The IgE-adsorptions were lowered by only 17% and 30% of the intact and glutaraldehyde-treated immunoadsorbents respectively after storage for 3 months in the 2% PO solution at 25°C, and these numbers are considered to be acceptable for a clinical use. A 2% PO solution was chosen based on the results of the shelf life test of immunoadsorbents and the sporicidal test of PO.
Urinary Prostaglandin E2 Excretion after the Resumption of Renal Function Post Renal Transplantation
Authors: Zawada E.T.
Published: March 2018

Previous studies have demonstrated that the renal prostaglandin system participate in the recovery from ischemic events, in diuresis and in natriuresis. This study was undertaken to probe renal prostaglandin E2 synthesis during the first and second weeks after renal transplantation

Urinary prostaglandin E2 excretion was greatly elevated immediately after transplantation, compared to the second week, and differences in urine PGE2 concentration were also significant. This suggests that enhanced prostaglandin synthesis accompanies the resumption of renal function after transplantation.
Studies of Complement Activation in ARDS Patients Treated by Long-Term Extracorporeal CO2 Removal
Authors: Cicardi M. Gardinali M. , Frangi D. , Bergamaschini L. , Gallazzi M. , Gattinoni L. , Agostoni A.
Published: March 2018

To investigate the role of complement activation in the adult respiratory distress syndrome (ARDS) and in the complications of extracorporeal circulation (ECC), several parameters (CH50, C3 split products, C3a, C5a, PMN aggregating activity, carboxypeptidase activity) of the complement profiles of 23 ARDS patients were measured.

Twenty patients were treated by long-term extracorporeal support. Before connection to ECC, marked leukocytosis (18,250 ± 5,950) and significantly high plasma C3a levels (p < 0.005) were observed. After connection, C3a levels increased further, up to values eight times higher than the basal ones.

The WBC count transiently decreased to 41% of prebypass levels after 15 minutes of ECC. At the same time C3 split products appeared and PMN aggregating activity was shown in 52% of the patients.

C5a levels remained normal during bypass, even in two samples in which PMN aggregating activity was detected. Later decreases in CH50 titers (p < 0.001) and carboxypeptidase activity (p < 0.005) were observed.

Complement activation was no longer evident after the 24th hour of bypass. We conclude that there is a low-degree complement activation in ARDS, and ECC is a further strong stimulus for complement activation. This phenomenon appears, however, to be self-limited.
Lymphocytapheresis in the Treatment of Rheumatoid Arthritis: Clinical and Immunological Studies
Authors: Indiveri F. , Rogna S. , Viglione D. , Pierri I. , Scudeletti M. , Grifoni V.
Published: March 2018

Six patients with Rheumatoid Arthritis (RA) have been treated with lymphocytapheresis after their disease proved unresponsive to conventional therapy.

Clinical improvement, measured evaluating articular swelling, morning stiffness, and muscle weakness, was observed in four of the six patients.

From the cellular point of view lymphocytapheresis induced (1) T cell depletion without modification of lymphocyte subsets in the peripheral blood, (2) improvement of lymphocyte responsiveness to lectins, autoantigens and alloantigens.

All together these data suggest that therapeutic leukapheresis modifies the immune responsiveness in humans, possibly facilitating the process of cell to cell cooperation.
Short and Long-Term Clinical Effects of Plasma-Exchange in 33 Cases of Myasthenia Gravis
Authors: Fornasari P.M. , Riva G. , Piccolo G. , Cosi V. , Lombardi M.
Published: March 2018

The Authors examine the results of plasma exchange (PE) treatment in 33 patients with myasthenia gravis, who underwent a total of 49 cycles of treatment. On the basis of clinical response, evaluated in relation to a modification of the functional state and to the duration of improvement after PE, we selected a group of 20 responsive patients (“responders” = 60.6%) and 13 non-responsive patients (“non-responders” = 39.4%). Positive effects, some only short-lasting, were observed in 24 patients (72.7%) after 32 cycles of a total of 49 cycles (65.3%). Out of the 11 most critical patients, 7 (63.6%) were considered responders, given the importance and duration of the improvement they presented, while 2 other patients had clear but short-lasting improvements; in these 9 patients, the positive effects amounted to 81.2%. Factors presumably responsible for therapeutic failure in the non-responders are discussed.
Experimental Considerations for the Centrifugal Separation of Blood Cell Components
Authors: van Wie B.J. , Sofer S.S.
Published: March 2018

Processing techniques using recycle and staging for blood cell collection lead to numerous conceptual design configurations. From a practical viewpoint, many of these schemes can become incongruous. Experimental fractional recoveries with up to six stages are presented, and material balance considerations and process comparisons are made. Isolation of specific leukocyte types, and cell viability effects are studied.
Combined Hemofiltration and Desferrioxamine Treatment for Aluminum Induced Osteomalacia
Authors: Barré P.E. , Prichard S.
Published: March 2018

A 61-year-old male hemodialysis patient developed the syndrome of aluminum intoxication including bone pain, fractures, proximal myopathy, progressive anemia and expressive aphasia. Serum aluminum was 130 micrograms/l and rose to 445 micrograms/l after the administration of 2 grams of desferrioxamine. Bone biopsy of the iliac crest revealed severe osteomalacia, heavy staining for aluminum and a bone aluminum content of 229 mg/kg dry bone. Treatment with combined hemofiltration and desferrioxamine administration led to a marked clinical improvement and a repeat bone biopsy striking healing of the osteomalacia with a bone aluminum content of 11 mg/kg dry bone.
Serum Antibody Titers in Rats Receiving Repeated Small Subcutaneous Injections of Hemoglobin or Polyhemoglobin: A Preliminary Report
Authors: Hertzman C.M. , Keipert P.E. , Chang T.M.S.
Published: March 2018

Cross-linking hemoglobin (Hb) into Polyhemoglobin (PolyHb) for use as an artificial blood substitute may affect its antigenicity. To investigate this, male Sprague-Dawley rats are immunized with one of the following: rat stroma-free Hb (rSFHb), rat PolyHb (rPolyHb), human stroma-free Hb (hSFHb), and human PolyHb (hPolyHb). Antibody titers are quantified using a double antibody radioimmunoassay. These results show that more antibodies are produced to hPolyHb than to hSFHb, whereas rSFHB and rPolyHb are relatively non-antigenic. Thus, under homologous conditions, cross-linking hemoglobin does not significantly increase its antigenicity, whereas under heterologous conditions the molecule becomes more antigenic.
Continuous Arterio-Venous Ultrafiltration in Cirrhotic Patients with Ascites or Renal Failure
Authors: Epstein Murray , Perez Guido O. , Bedoya Luis A. , Molina Reynaldo
Published: March 2018

To asses whether continuous arteriovenous ultrafiltration (CAVU) might constitute a useful alternative to hemodialysis in the management of patients with advanced liver failure, we carried out CAVU in 3 patients with decompensated Laennec's cirrhosis. CAVU was utilized in two patients with acute renal failure and pulmonary edema to stabilize renal function and facilitate administration of large amounts of fluid. In the third case, CAVU was successfully utilized to mobilize fluid in a patient refractory to conventional diuretic regimens. We conclude that CAVU may constitute an appropriate alternative to traditional hemodialysis in patients with advanced liver disease and renal functional impairment.
Efficacy of a Combined Treatment with Plasma Exchange and Cytostatics in Macroglobulinemia
Authors: Busnach G. , dal Col A. , Brando B. , Perrino M.L. , Brunatti C. , Minetti L.
Published: March 2018

Monthly plasma exchange (PE) sessions have been carried out in 3 patients with advanced Waldenström macroglobulinemia, in order to reduce electrophoretic M band under 2g/100 ml. When PE was combined to low doses of cytostatics (n=1 8), 3 procedures per session were required to obtain a mean 57.4±12.3% IgM reduction, from 4.2±1.2 to 1.7±0.5 g/100 ml.

A mean 61.5±13.1% IgM reduction, from 5.5±1.3 to 2.1±1 g/100 ml, was obtained in 64 procedures carried out as the only therapy in 12 sessions, with 5.3 procedures requirement per monthly session. IgM percent reduction 24 hours after PE was greater with combined treatment (45±9.7 vs. 28.9±1 5.4%; p=0.001).

The advantage of a combined treatment is therefore either a lowered PE requirement or a tapered maintenence cytostatic dosage.
Blood Detoxification and Other Therapeutical Alternatives in Nephrology
Authors: Becerra A. Treviño
Published: March 2018

The author summarizes a number of blood detoxification procedures with emphasis on hemoperfusion, hemodialysis and chronic ambulatory peritoneal dialysis.
Bioartificial Liver: Implanted Artificial Cells Microencapsulated Living Hepatocytes Increases Survival of Liver Failure Rats
Authors: Wong H. , Chang T.M.S.
Published: March 2018

Suspension of living hepatocytes were microencapsulated inside 300 micron mean diameter alginate artificial cells. The galactosamine fulminant hepatic failure rat model was used. 48 hours after the injection of galactosamine, grade II coma hepatic failure rats were divided into pairs. One of the pair was randomly chosen for the control group, and the other for the treated group. Each rat in the control group received one peritoneal injection of microcapsules containing no hepatocytes. Each rat in the treated group received one peritoneal injection of microcapsules containing hepatocytes. The survival of the treated group is significantly higher than the control group.
Successful Treatment of Experimental Neonatal Respiratory Failure Using Extracorporeal Membrane Lung Assist
Authors: Fumagalli R. , Kolobow T. , Arosio P. , Chen V. , Buckhold D.K. , Pierce J.E.
Published: March 2018

A total of 44 preterm fetal lambs at great risk of developing respiratory failure were delivered by Cesarean section, and were then managed on conventional mechanical pulmonary ventilation. Fifteen animals initially fared well, and 14 of these were long term survivors. Twenty-nine other lambs showed a progressive deterioration in arterial blood gases within 30 minutes of delivery, of which 10 lambs were continued on mechanical pulmonary ventilation (20% survival), while the remaining 19 lambs were placed on an extracorporeal membrane lung respiratory assist (79% survival). Extracorporeal membrane lung bypass rapidly corrected arterial blood gas values, and permitted the use of high levels of CPAP instead of the continuation of mechanical pulmonary ventilation at high peak airway pressures. Improvement in lung function was gradual, and predictable.

Early institution of extracorporeal respiratory assist using a membrane artificial lung rapidly corrected arterial blood gas values and significantly improved on neonate survival.
Plasmapheresis in Acute Liver Failure
Authors: Freeman J.G. , Matthewson K. , Record C.O.
Published: March 2018

A series of 9 patients with acute hepatic failure and Grade IV hepatic coma received daily plasmapheresis until they recovered or death ensued. Of the nine, seven (77%) showed an improvement in coma grade and five (55%) survived to leave hospital. Plasmapheresis significantly decreased serum bilirubin, asparate aminotransferase and plasma ammonia concentrations. Survival following plasmapheresis appeared substantially better than in a non randomized group of similar patients not plasmapheresed. The simplicity of the procedure, biochemical improvements observed and apparent efficacy, suggest that further evaluation of the technique as a means of providing temporary hepatic support is indicated.
Effect on leukocyte locomotion and superoxide production by uremic toxins and polyamines
Authors: Farinelli A. , Fiocchi O. , Stabellini G. , Stabellini N. , Marangoni C. , Spisani S.
Published: March 2018

We have isolated peak II, which is the peak of the middle molecules containing polyamines, from dialysate of uremic patients in recirculating dialysis. We investigated the effect of total dialysate, chromatographic peaks, I, II, III, IV and commercial polyamines on polymorphonuclear leukocyte chemotaxis and superoxide production (i.e. phagocytic activity) in healthy and uremic patients. Polymorphonuclear chemotaxis was inhibited by total dialysate and peak II but not by polyamines; polyamines, total dialysate and peak II had no activity on polymorphonuclear phagocytosis.
A Randomized Study of On-Line Plasma Perfusion over Protein A-Sepharose and 5-Fluorouracil Chemotherapy in Patients with Metastatic Colorectal Carcinoma
Authors: Faradji A. , Bohbot A. , Damonte J. , Arnaud J.P. , Eber M. , Laustriat D. , Goetz J. , Wiesel M.L. , Follea G. , Piemont Y. , Bergerat J.P. , Cazenave J.P. , Adloff M. , Oberling F.
Published: March 2018

To evaluate the safety of on-line plasma perfusion over protein-A sepharose and the therapeutic advantage of combining plasma perfusion (PP) over protein-A sepharose with 5-fluorouracil (5-FU) chemotherapy in patients with metastatic colorectal carcinoma (MCRC), thirty patients were randomized after surgery of primary CRC to receive a combination of 5-FU and PP over protein-A sepharose (group A), or a combination of 5-FU and PP over sepharose (group B), or 5-FU alone (group C). Bi-weekly on-line PP over 200 ml protein-A sepharose gel (group A) or 200 ml sepharose gel (group B) were performed with a Cobe 2997 blood cell separator for a maximum of 19 treatments per patient. 5-FU was given at 1000 mg/m2/d on days 1-5 of a 4-weekly cycle until progression. PP was well tolerated and no severe or life-threatening toxicity was observed. Mild clinical side-effects consisted of fever and chills (36% in group A, 23% in group B). The most common biological effects of PP over protein-A sepharose were significant drops in IgG (66% of pre-PP values), CH50 and C3 (73% of pre-PP values) and a significant generation of C3a and C5a anaphylatoxins. Tumor response rates were 40% for group A, 0% for group B and 20% for group C. The median survival times tended to be longer in group A (17 months) than in group B (10 months) and in group C (9 months). This is the first randomized trial showing some therapeutic advantage in combining PP over protein-A sepharose with conventional chemotherapy in MCRC.
Trace Elements and Plasmapheresis
Authors: Hosokawa S. , Oyamaguchi A. , Yoshida O.
Published: March 2018

The relationship between serum aluminum (Al), zinc (Zn), copper (Cu), and iron (Fe) and plasmapheresis (PP) treatment was examined. Three patients with rheumatoid arthritis, six with myasthenia gravis, and 6 with multiple sclerosis were studied. Serum Al, Zn, Cu, and Fe were measured before and after PP. Plasma was separated by first filtration; a second filtration separated the plasma components. Three liters of plasma were treated in each PP session. With each PP treatment, total protein (TP) removed was 20 ± 5% and serum albumin removed was ± 6%. Serum Al rose significantly (p < 0.01 from 1.1 ± 0.2 μgl dl pre-PP to 2.8 ± 0.4 μg/dl post-PP. Serum Zn, Cu, and Fe decreased significantly (p < 0.01) from 86.2 ± 7.4 μg/dl, 126 ± 18 μg/dl, and 108 ± 14 μg/dl pre-PP to 58.4 ± 10.2 μg/dl, 104 ± 6 μg/dl, and 82 ± 16 μg/dI post-PP, respectively.

Two days after the end of the six-month PP treatment, serum Al levels rose significantly (p < 0.01), from 1.1 ± 0.2 μg/dl to 3.6 ± 0.8 μg/dl. However, serum TP, serum albumin, and serum Zn, Cu, and Fe did not change significantly.

It thus appears essential in PP treated patients, to remove Al from the blood to protect against aluminum intoxication
Irreversible Drop of Systemic Vascular Resistances in Patients Implanted with a Jarvik Total Artificial Heart
Authors: Deleuze P. , Loisance D.Y. , Shiiya N. , Wan F. , Hillion M.L. , Benvenuti C. , Heurtematte Y. , Cachera J.P.
Published: March 2018

Maintenance of the body's perfusion by a total artificial heart (TAH) may result in physiological alterations to the circulatory system. Little has been said about modifications to systemic vascular resistances (SVR) during TAH assistance. This paper reports on two patients implanted with a Jarvik - 70 cc TAH, who died after 1 and 3 days, both with an irreversible drop of SVR related to a complete loss of vascular tone but not related to sepsis. Activation of multiple cascades of inflammation, triggered by the extracorporeal circulation (ECC), is maintained during TAH support. Desperately sick patients might not be able to face the vaso-active situations created by the inflammatory response.
Use of the Ultrafiltrate Obtained in Two-Chamber (Pfd) Hemodiafiltration as Replacement Fluid. Experimental ex vivo and in Vitro Study
Authors: Ghezzi P.M. , Botella J. , Sartoris A.M. , Gervasio R. , Diez C.
Published: March 2018

PFD (Paired Filtration Dialysis) is the only hemodiafiltration (HDF) technique in which the ultrafiltrate (UF) is continuously available not mixed with the dialysate. As with all convective or prevailingly convective techniques, a replacement fluid is necessary in an amount equal to the difference between the UF and the desired weight loss. This replacement fluid (R) must have an adequate electrolytic balance (Na+, Ca++, and buffer), and must be sterile and pyrogen-free. Using an uncoated adsorbent charcoal cartridge, we “regenerated” the UF obtained in PFD, eliminating the small (except for urea, which was later eliminated by diffusion in the dialyzing section of the PFD system) and the medium-to-large molecules (vit B12 and myoglobin in vitro and beta-2-microglobulin (B2m) and (hANP) in vivo), but not the electrolytes and the endogenous bicarbonate, so as to verify its possible use as R. This technique, experimentally performed in 12 patients under HDF treatment with standard PFD, with a total mean UF of 9650 ± 875 ml and the use of 130 g of uncoated charcoal, produced a solution with the following composition: Na+ 135.4 ± 2.4 mmol/l, K+ 3.4 ± 1.23 mmol/l, Ca++ 1.18 ± 0.14 mmol/l, HCO3- 26.7 ± 2.3 mmol/l, phosphates 2.88 ± 0.81 mg/dl, urea 63 ± 14 mg/dl, creatinine 0.08 ± 0.02 mg/dl, uric acid 0.05 ± 0.0 mg/dl, beta-2 microglobulin 0.5 ± 0.5 mg/l, and hANP 4.15 ± 5 pg/l. By integration with electrolytes (Na+, Ca++) and buffer, and changes in the composition of the dialysate, and considering that the K+ and phosphates, and urea, can all be removed by diffusion in the dialyzing section, PFD can be done using in its “regenerated” ultrafiltrate as an “endogenous” replacement fluid.
Right-Left Ventricular output Balance in the Totally Implantable Artificial Heart
Authors: Olsen D.B. , White R. Keith , Long J.W. , Khanwilkar P.S.
Published: March 2018

Pneumatically powered artificial hearts readily accommodated the higher net stroke volumes by the right ventricle than from the left ventricle. We published that this discrepancy was approximately 8% of the left ventricular cardiac output. A variety of methods have been used to achieve balance between the right and left atrial pressures. Relatively large volume-displacement chambers (VDC) present potential problems, but do provide balance. The VDC in volumetrically coupled right-left stroke volumes was eliminated by using a small-diameter interatrial shunt (IAS). Preliminary studies demonstrated excellent balance in contracted and expanded blood volume (preload) and by hypotension and hypertension created with vasoactive drugs (afterload). At a mean aortic pressure of 120 mmHg, heart rate of 120 BPM, cardiac output of 8 L/minute and right atrial pressure of 13 mmHg, the peak IAS flow was 3.2 ml/beat in a right to left direction and 8.0 ml/beat in a left to right direction. The net left to right flow was 4.8 ml/beat. Over a wide range of preload (2 to 20 mmHg) and afterload (45 to 180 mmHg), the left atrial pressure was routinely 5 mm Hg more than the right atrial pressure. Elimination of the VDC reduces the number of components, volume, and weight of the totally implantable artificial heart. The IAS offers a simple solution to a very complex problem and provides a device that is simpler to implant and is possible to explant.
Combined Recombinant Human Erythropoietin-Blood Letting Strategy for Treating Anemia and Iron Overload in Hemodialysis Patients
Authors: Agroyannis B. , Koutsicos D. , Tzanatou-Exarchou H. , Varsou-Papadimitriou E. , Kapetanaki A. , Yatzidis H.
Published: March 2018

We studied the feasibility of treating refractory anemia and post-transfusional serious hemochromatosis in a patient undergoing hemodialysis (3x4 h weekly) for fourteen years, with recombinant human erythropoietin (r-HuEPO) associated with blood-letting. Blood transfusion previously received by the patient at a rate of two units of packed red cells every month for nine years was stopped and r-HuEPO (80 U/kg b.w.) was administered i.v. at the end of each hemodialysis. When Hct increased over 30%, approximately 40 ml of blood was removed per hemodialysis session in an attempt to accelerate iron loss. Excellent control of anemia and hemochromatosis was achieved after seven months of treatment. The patient's general condition and skin pigmentation were significantly improved.
The Measurement of Blood Density to Investigate Protein Deposition at the blood/hollow Fiber Membrane Interface during Ultrafiltration
Authors: Dörp E. , Schneditz D. , Moser M.
Published: March 2018

Concentration polarization and secondary membrane formation change the membrane hydraulic permeability of capillary filters during hemofiltration reducing initial value filtration rates up to 50%. This leads to a significant loss of filter efficiency which must be taken into consideration when designing filters for long-term application such as in implantable artificial kidneys. By measuring blood density uninterrupted over a period of time using the mechanical oscillatory technique it is possible to follow the dynamics of protein deposition at the interface between the blood and capillary walls. The resulting picture of the deposition behaviour can lead to a better understanding of time-dependent filtration where flow and pressure conditions change. Protein deposition (Pt) with polysulfone membranes in relation to the effective capillary surface was in the range of 2.2. mg/(h x cm2) according to a logarithmic function (Pt = a + b x log(t)).