bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood - Artificial Surface Interactions during Cardiopulmonary Bypass
Authors: Benedetti M. , De Caterina R. , Bionda A. , Gardinali M. , Cicardi M. , Maffei S. , Gazzetti P. , Pistolesi P. , Vernazza F. , Michelassi C. , Giordani R. , Salvatore L.
Published: April 2018

Evaluation of the biocompatibility of four different types of oxygenator (bubble, membrane, hollow fibre and ‘hybrid’) was performed on 26 patients undergoing cardiopulmonary bypass during elective coronary surgery. More platelet derangement and an increased degree of hemolysis, revealed by higher plasmatic concentration of beta-thromboglobulin, platelet factor 4 and plasmatic free hemoglobin (p < 0.05), was seen when using the bubble oxygenator. Damage to blood cells was minimal with the membrane oxygenator while the ‘hybrid’ and the hollow fibre oxygenators proved to rank at an intermediate level. Complement activation at the beginning of the cardiopulmonary bypass occurred via the alternative pathway as demonstrated by C3adesarg increase (up to nine times) without a concomitant elevation of C4adesarg. Cardiopulmonary bypass complement activation was quantitatively similar with all the oxygenators. A further activation via the classical pathway occured in all the patients after protamine injection. Consistent differences as far as clinical and biological effects exist among the various commercially available cardiopulmonary bypass apparatus; our study provides guidelines for the evaluation and selection of devices which might reduce postoperative sequelae.
Development of a New Inflow Valve for a 20cc Semisoft Ventricle: Preliminary Results
Authors: Wijsmuller E.G. , Yu L.S. , Yuan B. , Bishop N.D. , Kolff W.J.
Published: April 2018

We remodeled and tested our semisoft 20cc ventricle and made a new bileaflet flap inflow valve. Housings, bases, outflow valve, and a newly designed diaphragm were all made by vacuum forming and put together by radiofrequency welding or glue. In vitro, the ventricle produced a cardiac output of 2.5 to 3.0 L/min and showed reliable durability results. Hematological testing showed no important thrombogenecity of the new valve. Cardiac output was higher than expected for the volume of the ventricle, perhaps because of stretching or flow through. Animal experiments with the left ventricular assist device (LVAD) version was done at Ohio State University. Earlier in Utah, we did 20 cc total artificial heart (TAH) implantations and LVAD experiments in lambs and recently in calves with the 60cc TAH version. A soft ventricle is easy to implant and low in production costs.
In Vivo Effects of Stroma-Free Hemoglobin and Polyhemoglobin on Coagulation Factors in Rats
Authors: Ning J. , Chang T.M.S.
Published: April 2018

We studied the effects of rat stroma-free hemoglobin (rSFH), human stroma-free hemoglobin (hSFH), rat polyhemoglobin (rPoly), and human polyhemoglobin (hPoly) on coagulation factors in rats. Albumin and saline infused rats were controls. The infusion volume was 10% of the rat's blood volume. The concentrations of hemoglobin in this study were 7 g/dl.

Measurements for prothrombin time (PT) and activated partial thromboplastin time (PTT) were at 5 minutes, 2, 6, 24 and 72 hours after infusion. Factor X, fibrinogen, plasminogen, antithrombin III, and antiplasmin were followed at 24 and 72 hours after infusion. Compared with saline infused rats PT and PTT did not change significantly in those rats infused with Hb preparations. There was a transient increase of PTT from 2 to 24 hours after infusion in albumin infused rats. Factor X, fibrinogen, antithrombin III and antiplasmin showed no significant differences between Hb infused groups and saline infused group. Twenty-four hours and 72 hours after infusion plasminogen decreased in all groups except the albumin infused rats at 24 hours after infusion when compared with normal rat plasma pool. However, there were no significant differences in plasminogen levels between the hemoglobin infused groups and the control saline group.

Stroma-free and polyHb solutions (rSFH, hSFH, rPoly and hPoly) did not cause significant changes in prothrombin time and activated partial thromboplastin time in rats. The rats infused with hemoglobin solutions (rSFH, hSFH, rPoly, and hPloy) did not show significant differences in Factor X, fibrinogen, antithrombin III and antiplasmin levels compared with the control group.
Comparison of two Methods for the Estimation of Urea Kinetics and Introduction of a Third Simplified Method
Authors: Vanholder R. , van Trimpont P. , Ringoir S.
Published: April 2018

It has been claimed that computed urea kinetic (UK) modelling in hemodialysed patients, for the estimation of protein intake, leads to an overestimation of protein catabolic rate (PCR). In the present study, three different methods of kinetic modelling for the determination of PCR and Kt/V are compared in 24 patients. The first method was the direct quantification method (DDQ) based on the collection of all urea eliminated from the body. The first computed method (ICMI) was the urea kinetic modelling method as described by Sargent. Dialyzer clearances were measured directly and not estimated by theoretical extrapolation. The second computed method (ICMII) is based on the indirect calculation of urea distribution volume (Vu), according to Watson, and of dialyzer clearances from this Vu and from pre- and post-dialysis urea concentrations. All three methods resulted in PCR's that were not significantly different (DDQ: 1.03 ± 0.19; ICMI: 1.04 ± 0.22; ICMII: 1.08 ± 0.25 mg/Kg BW.24 hrs; p > 0.05). When the results were correlated, the following results were obtained: ICMI vs ICMII: r = 0.89, p < 0.001; ICMI vs DDQ: r = 0.68, p < 0.01; DDQ vs ICMII: r = 0.78, p < 0.001. Intermutual comparison of Kt/V values resulted in virtually identical results, especially when comparing ICMI and ICMII, where the regression line equalled the identity line.

In conclusion, all methods seem equally reliable in determining mean PCR and Kt/V. Our data, obtained with directly measured dialyzer urea clearances, do not confirm the earlier held opinion that computed modelling results in an overstimation of PCR. The newly developed third method (ICMII) appears to be as equally reliable as the two other methods, but is easier to perform and less labour intensive.
Theoretical Model of Blood Flow through Hollow Fibres considering Hematocrit-Dependent, Non-Newtonian Blood Properties
Authors: Lerche D. , Oelke R.
Published: April 2018

Accounting for the non-Newtonian blood viscosity by the Quemada descriptive viscosity equation, we deduced velocity profiles and volumetric capillary flows from the Navier-Stokes-equation. An arbitrary axial and/or radial hematocrit profile can be chosen. The hematocrit dependence of the intrinsic viscosities ko (H) (characterizing, at least in part, the RBC aggregation) and k∞ (H) (describing orientation/deformation of RBC) was taken into account.

Velocity profiles for pressure gradients of 4-4000 Pa/cm show a distinct flattening, if a pronounced axial migration of RBC is assumed. The higher the axial concentration, the higher the flow at the same pressure gradient. Small deviations (≤ 10%) of the capillary number per dialyzer or of the radius of capillaries lead to a strong change of the pressure gradient with the same dialyzer flow. Whereas small hydraulic conductivities do not significantly change this gradient, high conductivities decrease the pressure gradient by about 10%. Impaired blood flow properties (hemoconcentration) result in a slight deviation from the linear axial pressure drop.
Bone Marrow Erythroid Precursor Ca++ Regulates the Response to Human Recombinant Erythropoietin (Rhuepo) in Hemodialysis Patients
Authors: Carozzi S. , Ramello A. , Nasini M.G. , Schelotto C. , Caviglia P.M. , Cantaluppi A. , Salit M. , Lamperi S.
Published: April 2018

The modulation of erythropoiesis by erythropoietin is conditioned by the concentration of Ca++ in the cytoplasm of the bone marrow erythroid precursors. We evaluated in vitro erythroid colony development from bone marrow erythroid precursors incubated with increasing concentrations of Ca++ or Ca++ plus 1,25 (OH)2 D3, and bone marrow erythroid precursor cytoplasmic Ca++ concentrations in 10 anemic hemodialysis (HD) patients before and during rHuEPO therapy. Results showed that: a) in vitro: in uremics patients before rHuEPO therapy, bone marrow erythroid precursor cytoplasmic Ca++ was lower than in normal subjects; the addition of Ca++ to the bone marrow erythroid precursors induced a dose-dependent Ca++ and erythroid colony development increase; 1,25 (OH)2 D3 potentiated this effect; b) in vivo: rHuEPO normalized bone marrow erythroid precursor Ca++ and erythroid colony development. An inverse correlation was seen between bone marrow erythroid colony development, precursor CA++ before therapy, the in vitro erythroid and the rHuEPO dose needed in vivo to normalize hematological parameters. These data emphasize the role of Ca++ in erythropoiesis and may aid understanding of the mode of action of rHuEPO in HD.
Development and Evaluation of a Pliable Biological Valved Conduit. Part I: Preparation, Biochemical Properties, and Histological Findings
Authors: Noishiki Y. , Hata C. , Tu R. , Shen S.H. , Lin D. , Sung H.W. , Witzel T. , Wang E. , Thyagarajan K. , Tomizawa Y. , Quijano R.C.
Published: April 2018

Different types of external valved conduits have been used for the repair of complex congenital cardiac anomalies that may have otherwise been inoperable. However, an ideal conduit has yet to be found due to complications such as stenosis, thrombosis, calcification of the valve and graft wall, and “peeling” of the neointima. To address those problems, a new extracardiac valved conduit made of bovine jugular vein was developed and evaluated in a preliminary animal study. Harvested bovine vein containing a naturally existing valve was initially incorporated with protamine on the inner surface and then was cross-linked in diglycidyl ether (DE). Fixation with DE allowed the vein and its leaflets to retain a tissue-like elasticity. To provide antithrombogenicity to the graft, heparin was introduced into the lumen to bind ionically to the pre-entrapped protamine. The biological valved conduit of approximately 14 mm diameter was implanted from the right ventricle to pulmonary artery as bypass graft in three dogs. After implantation, the native main pulmonary artery was ligated between the anastomotic sites of the bypass conduit. No anticoagulant or antiplatelet drugs were administered after surgery. One DE-fixed valved conduit was retrieved at 3 months, and the others were removed at 5 months. Only small thrombus areas were found on the white luminal surfaces. The valves and the conduits maintained softness and pliability, similar to before implantation. Additionally, the collagen content, shrink temperature, and tanning index of this newly developed biological valved conduit before and after fixation were measured in the study. These preliminary results suggest that the new valved conduit fixed with DE and heparinized on the lumen may help mitigate the problems observed in the currently available conduits.
Development and Evaluation of a Pliable Biological Valved Conduit. Part II: Functional and Hemodynamic Evaluation
Authors: Sung H.W. , Witzel T.H. , Hata C. , Tu R. , Shen S.H. , Lin D. , Noishiki Y. , Tomizawa Y. , Quijano R.C.
Published: April 2018

Many congenital cardiac malformations may require a valved conduit for the reconstruction of the right ventricular outflow tract. In spite of many endeavors made in the last 25 years, the clinical results of right ventricular outflow tract reconstruction with currently available valved conduits are still not satisfactory. Specific problems encountered clinically include suboptimal hemodynamic performance, conduit kinking or compression, and fibrous peeling from the luminal surface. To address these deficiencies, we undertook the development of a biological valved conduit: a bovine external jugular vein graft with a retained native valve cross-linked with a diglycidyl ether (DE). This study, using a canine model, was to evaluate the functional and hemodynamic performance of this newly developed valved conduit. Three 14 mm conduits, implanted as bypass grafts, right ventricle to pulmonary artery, were evaluated. The evaluation was conducted with a noninvasive color Doppler flow mapping system at pre-implantation, immediately post implantation, one- and three-months post implantation, and prior to retrieval (five-months post implantation). The two-dimensional tomographic inspection of the leaflet motion at various periods post implantation showed that the valvular leaflets in the DE treated conduit was quite pliable. No cardiac failure or valvular dysfunction was observed in any of the studied cases. The color Doppler flow mapping study demonstrated that the valve in the DE treated conduit was competent, with no conduit kinking or compression observed in any of the three cases. The spectral Doppler velocity study evidenced that the transvalvular pressure gradients of the DE treated conduit were minimal as compared to those of the currently available conduits. In conclusion, from the functional and hemodynamic performance points of view, this newly developed valved conduit is superior to those currently available.
Obstacles in the Application of Microencapsulation in Islet Transplantation
Authors: De Vos P. , Wolters G.H.J. , Fritschy W.M. , Van Schilfgaarde R.
Published: April 2018

Several factors stand in the way of successful clinical transplantation of alginate-polylysine-alginate microencapsulated pancreatic islets. These obstacles can be classified into three categories. The first regards the technical aspects of the production process. Limiting factors are the insufficient ability to produce small capsules with an adequate production rate, and insufficient insight into the factors determining the optimal chemical and mechanical properties of the capsules. The second category regards the functional aspects of the microencapsulated islets, such as the limitations of the transplantation site and the absence of a physiologic insulin response of the encapsulated islets to elevated blood glucose levels. The third category regards the fact that survival times of encapsulated islet grafts are still limited to several weeks or months, which is mainly explained by a pericapsular fibrotic overgrowth reaction as a consequence of the bioincom-patibility of the capsule membrane. This study describes these obstacles, and thereby summarizes the requirements needed for successful clinical application of encapsulated islet transplantation.
Extracorporeal Enzymatic Removal of Low Density Lipoproteins in Rabbits: Efficacy and Safety
Authors: Shefer S.D. , Ferreira J. , Mullon C. J-P. , Langer R.
Published: April 2018

An extracorporeal circuit incorporating a plasma separator reactor (PSR) was designed to modify low density lipoproteins (LDL). The PSR was tested in vivo with hypercholesterolemic New Zealand White rabbits. The bioreactor enzymatically converts LDL to a form that can be removed by the body at an enhanced rate. The physiological response of hypercholesterolemic New Zealand White rabbits to 90 minute extracorporeal treatments was monitored. The total plasma cholesterol concentration in the treated rabbits fell sharply (up to 40% decrease) during and following the treatment. Results of safety tests indicate no significant enzyme leaching from the device, no disruption or damage to erythrocytes, no increase in white blood cell count and no liver damage as indicated by five enzyme assays. All safety measurements suggest that the treatment is safe.
Catheter-Implanted Prosthetic Heart Valves
Authors: Knudsen L.L. , Andersen H.R. , Hasenkam J.M.
Published: April 2018

A new expandable artificial heart valve was developed for implantation by a transluminal catheter technique without using thoracotomy or extracorporeal circulation. The aim of this study was to implant the valve in isolated vessels of the descending thoracic aorta as well as in closed chest pigs, and furthermore to study the prosthesis’ mechanical stability and the valve function. The artificial valve was made by mounting a porcine aortic valve on an expandable stent. Before implantation, the stent-valve was compressed on a deflated balloon catheter and mounted inside an introducer sheath. After intravascular introduction to the descending thoracic aorta the stent-valve was discharged from the sheath. Implantation was performed by balloon inflation which expanded the stent-valve to a diameter exceeding the internal vessel's diameter. After balloon deflation the stent-valve maintained an expanded configuration ensuring a stable fixation against the vessel wall. In vitro implantations were performed in 36 isolated descending thoracic aorta specimens obtained from 80 kg pigs. Mechanical stability was evaluated by applying a downing load to the prosthesis. No displacement occurred at loads ≤ 1 kg when a large balloon (31 mm) was used for implantation. Transvalvular pressure differences between 11-47 mmHg (median) were obtained at antegrade flowrates between 5-8 1/min. Furthermore, only moderate leakage flows were measured during retrograde perfusion. In vivo implantations were performed in six 80 kg pigs. Implantation was safe and easy, and angiograph and haemodynamic evaluations revealed essentially no stenosis or regurgitation. No complications in migration, perforation, hemorrhage or thrombosis were observed. This study indicates a good mechanical stability and valve function of the new expandable artificial valves.
Heparinization of Biological Vascular Graft Reduces Fibrin Deposition
Authors: Boerboom L.E. , Olinger G.N. , Karas B.J. , Lindon J.N. , Rosen L.Z. , Thyagarajan K. , Tu R.
Published: April 2018

An alternative graft is needed for coronary bypass operations in patients lacking suitable autologous vessels. We therefore studied Denaflex™, a biologic graft, in a dog ex-vivo shunt model to determine whether heparin treatment makes this graft less thrombogenic. Comparison was also made to Bioflow™, a nonheparinized biologic graft. Fibrinogen deposition during high flow (593 ± 202 ml/min) decreased from 672 ± 467 ngl mm2 in nonheparinized Denaflex grafts to 448 ± 298 ng/mm2 (p<0.05) in heparinized Denaflex grafts. At low flow (117 ± 13 ml/min), heparinization of Denaflex grafts similarly decreased fibrinogen deposition from 1102 ± 601 ng/mm2 to 703 ± 405 ng/mm2 (p<0.05). At both flow rates fibrinogen deposition in Bioflow grafts was less than in nonheparinized Denaflex, but was similar to heparinized Denaflex grafts. Platelet deposition was not influenced by heparinization of Denaflex grafts and was similar among Denaflex and Bioflow preparations. Whether Denaflex performs acceptably in vivo as a xenograft requires extensive study.
Morphological Response of the Peritoneum and Spleen to Intraperitoneal Biomaterials
Authors: Guo W. , Willén R. , Andersson R. , Pärsson H. , Liu X. , Johansson K. , Bengmark S.
Published: April 2018

The present study was performed to evaluate the morphological response of the peritoneum and spleen to biomaterials. Silicone elastomer, knitted dacron or rubber was implanted, respectively, into a rat's peritoneal cavity and the morphology of the peritoneum and spleen was studied at 4 hours and on the 1st, 4th, 7th and 21st day after surgery. The morphological changes were identical among groups with different implanted materials. After intraperitoneal implantation of biomaterials from 4 hours and on, an infiltration of inflammatory cells was found in the slackened edematous superficial part of the peritoneum. Also noted in the spleen were stasis, vessel dilatation and fibrin deposition. With the help of scanning electron microscopy, a marked denudation and separation of the mesothelial cells, with infiltration of inflammatory cells, were observed. Peripheral leucocytes significantly increased in number one day after intraperitoneal implantation. Three weeks after intraperitoneal implantation, the materials were completely encapsulated and the morphological aberration of the peritoneum and spleen disappeared. The findings reveal the consequence and the resolution of the host-biomaterial interaction, which could contribute to the explaination of various pathophysiological alterations, including the translocation of enteric bacteria and the development of infectious complications after intraperitoneal biomaterial implantation.
Correction of Anemia Using Self-Administered Daily Subcutaneous Erythropoietin in Uremic Patients on Continuous Ambulatory Peritoneal Dialysis
Authors: Li P.K.T. , Leung C.B. , Lui S.F. , Leung J.C.K. , Shek A.C.C. , Lai K.N.
Published: April 2018

We studied the effects of self-administered, daily, low-dose, subcutaneous (SC) erythropoietin (EPO) therapy in 15 uremic patients on continuous ambulatory peritoneal dialysis (CAPD) for 16 weeks to assess its efficacy and safety. The patients had baseline hemoglobin (Hb) levels of <8 g/dl and were started on 10 u/kg/day of beta-EPO. The dosage of EPO was adjusted every 4 weeks according to hematological response. The patients learned to inject into their thighs themselves. Hb increased significantly from 6.6 ± 0.2 g/dl (mean ± SEM) at week 0 to 9.0 ± 0.3 at week 8 and 10.0 ± 0.4 at week 16 (p < 0.0001). Hematocrit (Hct) increased significantly from 0.20 ± 0.01 at week 0 to 0.27 ± 0.01 at week 8 and 0.29 ± 0.001 at week 16 (p < 0.0001). The mean EPO dose was 10 u/kg/day at week 0 and 10.5 ± 0.4 at week 8 and 10.3 ± 0.5 at week 16. After minor adjustments in antihypertensive therapy had been made no significant differences in mean arterial blood pressure were noted. Six of 15 patients required increased dosage of antihypertensive drugs. All patients were given oral iron supplements. There was a significant drecrease in percentage of transferrin saturation and 10 patients required additional intravenous iron supplements. There was no significant difference in the serum levels of creatinine, albumin, potassium, phosphate and urate with EPO treatment. There were no local complications at the sites of injection and the injections themselves were quite painless. We conclude that low-dose SC daily EPO is effective and safe in the correction of anemia in CAPD patients.
A Preliminary Study of the Fixation Mechanism of Collagen Reaction with a Polyepoxy Fixative
Authors: Tu R. , Quijano R.C. , Lu C.L. , Shen S. , Wang E. , Hata C. , Lin D.
Published: April 2018

A new biomaterial has been developed by fixing native collagens with a polyepoxy compound (PC) fixative. Prior studies have shown that this biomaterial has comparable properties as compared to collagen fixed with glutaraldehyde (GA) and thus has a great promise for use as an implantable bioprosthesis. The purpose of this study was to understand the mechanism of the amino acids-PC reactions in the fixation process. Bovine arteries were fixed with PC under various pH, concentration and temperature conditions as a function of fixation time. Individual amino acid components in the fresh and the fixed arteries were assayed using a Beckman amino acid analyzer to determine the degree of tanning. The denaturation temperature (Td) was also measured on each sample. Since the denaturation temperature is a direct indication of cross-linking of individual amino acids with the fixative, the difference in the degree of tanning for the same increase in Td may be indicative of the quantity of the masked, non-cross-linked amino acids. The fixation reaction data indicated that not all amino acids were cross-linked upon contacting the PC fixative. Masking appeared to be more substantial with a fixation at higher pH values.
Oxygen Transport Capacity and Hemodynamic Effect of Newly Developed Artificial Blood “Neo Red Cells (NRC)”
Authors: Usuba A. , Miyazawa M. , Motoki R. , Sakaguchi K. , Suzuki K. , Kamitani T. , Takahashi A.
Published: April 2018

The purpose of this study was to evaluate liposome-encapsulated hemoglobin, named Neo Red Cells (NRC), on hemodynamics and oxygen-transport capacity in a blood exchange experiment. The experiment was carried out in nine mongrel dogs. Depending on the percentage of blood exchange with NRC, the animals were divided into two groups; Group I (4 animals with an exchange rate less than 88%), and Group II (5 animals with an exchange rate over 88%). After blood exchange, total peripheral vascular resistance index (TPRI) decreased and cardiac index (CI) increased. These changes were more marked in Group II than in Group I, thus showing that NRC relieved the burden on the heart, probably due to the fact that the viscosity of NRC is 2 cp which is less than 1/3 that of whole blood. The oxygen binding capacity per 1g hemoglobin in NRC was 2-4 times as much as red blood cells. Thus, NRC was superior to natural red blood cells in terms of oxygen transport capacity and its effects on the circulatory system.
Continuous Veno-Venous Hemofiltration in Critically Ill Patients with Multiple Organ Failure
Authors: Vesconi S. , Sicignano A. , De Pietri P. , Foroni C. , Minuto A. , Bellato V. , Riboni A.
Published: April 2018

18 critically ill patients, with multiple organ failure (MOF) (from shock either septic, n = 15, or cardiogenic, n = 3), oliguria and increase in BUN and creatinine were treated with pump driven, high flux continuous veno-venous hemofiltration (CVVH). Replacement fluids were administered in predilution mode. All patients were under respiratory support and vasoactive drugs, and received early nutritional support (N input: 0.2–0.3 g/kg/day). Mean duration of treatment was 9.2 days and mean ultrafiltrate production was 21.4 l/day; treatment resulted in a significant reduction of both urea nitrogen and creatinine blood levels (-20 and -40% of initial values respectively) in spite of a very severe catabolism. The total amount of urea nitrogen removed through CVVH ranged from 15 to 73 g/day (mean 33.5), the median value of urea nitrogen clearance was 12.8 ml/min with a median ultrafiltration coefficient of 0.8. The mean duration of hemofilters was 69 hours (38–108); the efficacy of filters remained stable throughout the entire lifespan and changes were made in case of sudden decrease of ultrafiltration (< ml/min). No major complication was observed in over than 4000 hours of treatment. Pump driven, high flux CVVH proved effective in the control of water electrolyte balance and metabolic homeosthasis in a group of critically ill, hemodynamically unstable, catabolic patients with MOF and acute renal failure. In no case we had to add intermittent hemodialysis or to use hemodiafiltration. The constant extracorporeal blood flow and the stable efficacy of hemofilters allowed an easy control of the overall effectiveness of this technique.
Side Effects of Hybrid Liver Support Therapy: TNF-α Liberation in Pigs, Associated with Extracorporeal Bioreactors
Authors: Gerlach J. , Jörres A. , Trost O. , Hole O. , Vienken J. , Courtney J.M. , Gahl G.M. , Neuhaus P.
Published: April 2018

During acute liver failure, hybrid liver support therapy could serve as a bridge to liver transplantation. In this desired temporary use, immune competent cell responses, such as the production of cytokines, might be of limiting relevance. We have investigated the Tumor Necrosis Factor-α (TNF) liberation in two models using pigs, connected with an extracorporeal bioreactor with homologous hepatocytes: TNF liberation was measured in arterial plasma during a 4 day perfusion time in untreated animals, model (i), and during short term perfusion of hepatectomized pigs in model (ii). Animals four days after catheter implantation in model (i) had TNF values of < 5 pg/ml. After connecting the system without hepatocytes, TNF rose to 9.7 ± 2 within 120 min and rose further to 32.6 ± 6 pg/ml within 4 hours after filling the system with the homologous hepatocytes. After 24 hours of continuous perfusion and during four days of perfusion, the TNF levels were lowered to baseline levels. In model (ii), TNF rose to 220 ± 130 pg/ml within 180 min and decreased to 110 ± 10 pg/ml within six hours, whereas controls without hepatocytes showed mean levels with a maximum of 120 ± 20 pg/ml. In both models, there was no correlation between TNF levels and clinical abnormalities such as fever or shock symptoms. There is evidence for an activation of blood cells during experimental extracorporeal hybrid support. No typical side effects were, however, observed. Thus, TNF mediated extracorporeal cell activation does not appear to limit the application of homologous hybrid liver support therapy.
Factors Influencing Arteriovenous Fistula Dysfunction in Japanese Patients on Chronic Hemodialysis
Authors: Masaki T. , Yorioka N. , Kyuden Y. , Yamashita K. , Taniguchi Y. , Yamakido M. , Tanaka J. , Harada S.
Published: April 2018

Arteriovenous fistula dysfunction is a constant problem in chronic hemodialysis patients. We investigated the factors influencing fistula dysfunction in 184 patients on chronic hemodialysis. Stepwise regression analysis and Cox proportional hazards model were used to assess the relationship between fistula dysfunction and age, sex, duration of hemodialysis, diabetes mellitus, hematocrit, serum creatinine, blood urea nitrogen, KW, prothrombin time, blood pressure, anticoagulant therapy, dose of erythropoietin, calcium channel blocker therapy, and angiotensin-converting enzyme inhibitor therapy. Fistula dysfunction showed a significant relationship with a low systolic blood pressure, a low hematocrit, the presence of diabetes mellitus, and angiotensin-converting enzyme inhibitor therapy. These results suggested that treatment with angiotensin-converting enzyme inhibitors may help to prevent fistula dysfunction.
Time-related Contact Angle Measurements with Human Plasma on Biomaterial Surfaces
Authors: Rakhorst G. , Van Der Mei H.C. , Van Oeveren W. , Spijker H.T. , Busscher H.J.
Published: April 2018

Axisymmetric drop shape analysis by profile (ADSA-P) was used to assess in time contact angle changes of human plasma drops placed on four different biomaterials. Results were related with conventional blood compatibility measurements: albumin adsorption, fibrinogen adsorption and platelet adhesion. While contact angle measurements with water are material-related but constant in time, contact angle measurements with plasma changed over time owing to protein adsorption on the solid-liquid interface. The contact medium plasma did not influence the initial contact angle. Contact angles on PDMS decreased most in time (41 degrees) and demonstrated highest levels of conventionally measured albumin and fibrinogen adsorption and platelet adhesion. PTFE, with the lowest contact angle decrease over a 500 minutes period (19 degrees), showed low fibrinogen and albumin adsorption as well as low platelet adhesion. PU and HDPE demonstrated almost similar initial contact angles with plasma and contact angle decreases (26 and 27 degrees), intermediate protein adsorption, and platelet adhesion. We conclude that biocompatibility properties of the tested materials may be more related to the behaviour of their contact angles in time, than to the initial hydrophobic or hydrophilic state.
Reducing perioperative blood loss in patients undergoing total hip arthroplasty
Authors: D'ambrosio A. , Borghi B. , Damato A. , D'amato G. , Antonacci D. , Valeri F.
Published: April 2018

In this prospective, randomised, double-blind study, we investigated the effect of epidural anaesthesia and an antifibrinolytic agent, Aprotinin (500,000 KIU in bolus before surgery and 500,000 KIU h-1 in drip form during surgery), on intra and postoperative blood loss and transfusion requirements in total hip arthroplasty. Sixty patients were allocated randomly to four groups (A: epidural + general anesthesia + Aprotinin, B: epidural + general anesthesia + placebo (equal volume), C: general anaesthesia + Aprotinin, D: general anaesthesia + placebo). Postoperative analgesia: epidural analgesia in groups A and B, systemic analgesia with opiates in groups C and D.

Blood loss during surgery was monitored and salvaged with the Compact-A Dideco, and postoperative blood loss with the BT 797 Recovery Dideco for the first 24 hours. Perioperative blood loss, frequency and quantity of transfusions were significantly higher in group D (p < 0.0001). Total blood loss was reduced by 31.3% by epidural anaesthesia, 20.4% by Aprotinin and 51.4% using a combination of the two techiniques.
Development of Experimental Setup for Measuring the Thermal Conductivity of Textiles
Authors: Siddiqui Muhammad Owais Raza , Sun Danmei
Published: April 2018

The thermophysical properties of textile materials are very important in helping to understand the thermal comfort of fabrics for clothing and technical textiles. An experimental setup for the measurement of the thermal conductivity of fabrics was developed based on the heat flow meter principle. The setup was considered highly accurate and reliable based on the low absolute error, high correlation coefficient, and the coefficient of determination between the results from the setup and commercially available devices. The setup is easy to use for testing any textile-based materials and their composites.
Unsteady reactive magnetic radiative micropolar flow, heat and mass transfer from an inclined plate with Joule heating: A model for magnetic polymer processing
Authors: Shamshuddin MD , Mishra SR , Bég O Anwar , Kadir A
Published: April 2018

Magnetic polymer materials processing involves many multi-physical and chemical effects. Motivated by such applications, in the present work, a theoretical analysis is conducted of combined heat and mass transfer in unsteady mixed convection flow of micropolar fluid over an oscillatory inclined porous plate in a homogenous porous medium with heat source, radiation absorption and Joule dissipation. A first-order homogenous chemical reaction model is used. The transformed non-dimensional boundary value problem is solved using a perturbation method and Runge–Kutta fourth-order numerical quadrature (shooting technique). The emerging parameters dictating the transport phenomena are shown to be the gyro-viscosity micropolar material parameter, magnetic field parameter, permeability of the porous medium, Prandtl number, Schmidt number, thermal Grashof number, species Grashof number, thermal radiation–conduction parameter, heat absorption parameter, radiation absorption parameter, Eckert number, chemical reaction parameter and Eringen coupling number (vortex viscosity ratio parameter). The impact of these parameters on linear velocity, micro-rotation (angular velocity), temperature and concentration are evaluated in detail. Results for skin friction coefficient, couple stress coefficient, Nusselt number and Sherwood number are also included. Couple stress is observed to be reduced with stronger magnetic field. Verification of solutions is achieved with earlier published analytical results.
Analysis of ground handling characteristic of aircraft with electric taxi system
Authors: Huang Mingyang , Nie Hong , Zhang Ming
Published: April 2018

Electric landing gear drive equipped with traction motors can provide taxi capability without the use of main engines or tractor. The ground handling characteristic of aircraft with electric taxi system is analyzed. The new mathematic model of aircraft ground maneuver is established, considering the 6-degree-freedom aircraft body and the flexible main strut and the powered wheel. Quasi-steady method is applied to calculate tire side forces and moments, to determine side slip. The simulation for the ground steering response of aircraft with electric taxi system is done by employing ADAMS and Simulink co-simulation platform. The dynamic responses of aircraft ground steering and landing gear spin-up and spring back are simulated. Different taxi conditions including powered nose wheel mode and powered main wheel mode are compared. Four conclusions are obtained: electric taxi system helps the aircraft turn on the spot and the turning radius is smaller than the aircraft using engines; differential powered main wheel mode has the minimum turning radius while turning-circle with uniform velocity, and it has smaller difference between two vertical loads of main landing gear than powered nose wheel mode; in the case of the same steering angle, the extreme velocity of differential powered main wheel mode before side slip is larger than powered nose wheel mode; and pre-rotation of powered main wheel decreases the spin-up drag load and spring back drag load.
Natural history of longitudinally extensive transverse myelitis in 35 Hispanic patients with systemic lupus erythematosus: good short-term functional outcome and paradoxical increase in long-term mortality
Authors: Flores-Silva F D , Longoria-Lozano O , Aguirre-Villarreal D , Sentíes-Madrid H , Vega-Boada F , Díaz de León-Sánchez E , Murra-Antón S , Morales-Moreno S , Quintanilla-González L , Fragoso-Loyo H , Guraieb-Chaín P , Higuera-Calleja J , Ceballos-Ceballos J , Treviño-Frenk I , González-Duarte A , Dávila-Maldonado L , Cantú-Brito C , Valdés-Ferrer S I
Published: April 2018

Background and objective

Acute transverse myelitis (TM) is an infrequent neurological complication of systemic lupus erythematosus (SLE). Short-term outcome varies widely between cohorts. Little is known about the epidemiology and long-term functional outcome of TM associated to SLE.

Methods

Patients with SLE and acute TM were identified during hospital admission, visits to the Emergency Room or the Neurology Outpatient Clinic. We evaluated ambispectively those patients with SLE presenting with clinical myelopathy and corroborated with spinal MRI. Cases were divided as partial (non-paralyzing) or complete (paralyzing). We determined long-term functional outcome as well as mortality in those patients with follow-up periods of at least five years.

Results

We identified 35 patients (partial, n = 15; complete, n = 20) in which complete clinical and imaging data were available (26 with follow-up ≥ 5 years). Patients with complete TM were significantly older than those with partial forms. Positive antiphospholipid antibodies were observed in 80% of patients, suggesting a possible mechanistical role. Surprisingly, functional recovery at one year was in general good; however, we observed a five-year mortality of 31% because of sepsis (in 10 cases) or pulmonary embolism (in one case).

Conclusions

Short-term outcome of SLE-related TM is generally good, and recurrence rate is low. However, we observed a long-term fatality rate of 31% for reasons unrelated to TM, suggesting that TM is a manifestation of severe immune dysregulation and a predictor of severity and mortality in patients with SLE.
Extended negative binomial hurdle models
Authors: Noh Maengseok , Lee Youngjo
Published: April 2018

Poisson models are widely used for statistical inference on count data. However, zero-inflation or zero-deflation with either overdispersion or underdispersion could occur. Currently, there is no available model for count data, that allows excessive occurrence of zeros along with underdispersion in non-zero counts, even though there have been reported necessity of such models. Furthermore, given an excessive zero rate, we need a model that allows a larger degree of overdispersion than existing models. In this paper, we use a random-effect model to produce a general statistical model for accommodating such phenomenon occurring in real data analyses.
An omnibus test for the global null hypothesis
Authors: Futschik Andreas , Taus Thomas , Zehetmayer Sonja
Published: April 2018

Global hypothesis tests are a useful tool in the context of clinical trials, genetic studies, or meta-analyses, when researchers are not interested in testing individual hypotheses, but in testing whether none of the hypotheses is false. There are several possibilities how to test the global null hypothesis when the individual null hypotheses are independent. If it is assumed that many of the individual null hypotheses are false, combination tests have been recommended to maximize power. If, however, it is assumed that only one or a few null hypotheses are false, global tests based on individual test statistics are more powerful (e.g. Bonferroni or Simes test). However, usually there is no a priori knowledge on the number of false individual null hypotheses. We therefore propose an omnibus test based on cumulative sums of the transformed p-values. We show that this test yields an impressive overall performance. The proposed method is implemented in an R-package called omnibus.
Bootstrap-based testing approaches for the assessment of the diagnostic accuracy of biomarkers subject to a limit of detection
Authors: Franco-Pereira Alba M , Nakas Christos T , Leichtle Alexander B , Pardo M Carmen
Published: April 2018

Assessment of the diagnostic accuracy of biomarkers through receiver operating characteristic curve analysis frequently involves a limit of detection imposed by the laboratory analytical system precision. As a consequence, measurements below a certain level are undetectable and ignoring these is known to lead to negatively biased estimates of the area under the receiver operating characteristic curve. In this article, we introduce two receiver operating characteristic curve-based parametric approaches that tackle the issue of correct assessment of diagnostic markers in the presence of a limit of detection. Proposed approaches are simulation-based utilising bootstrap methodology. Non-parametric alternatives that are naively used in the literature do not solve the inherent problem of limit of detection values which are treated as censored observations. However, the latter seems to perform adequately well in our simulation study. Nonparametric bootstrap was consistently used throughout, while other bootstrap alternatives performed similarly in our pilot simulation study. The simulation study involves the comparison of parametric and non-parametric options described here versus alternative strategies that are routinely used in the literature. We apply all methods to a study-setting resembling a chemical quasi-standard situation, where compound tumour biomarkers were searched within a multi-variable set of measurements to discriminate between two groups, namely colorectal cancer and controls. We focus in the assessment of glutamine and methionine.
Effect of Cinnamomum osmophloeum Kanehira Leaf Aqueous Extract on Dermal Papilla Cell Proliferation and Hair Growth
Authors: Wen Tung-Chou , Li Yuan-Sheng , Rajamani Karthyayani , Harn Horng-Jyh , Lin Shinn-Zong , Chiou Tzyy-Wen
Published: April 2018

In this study, we explored the effect of the water extract of Cinnamomum osmophloeum Kanehira (COK) leaves on hair growth by in vitro and in vivo assays. Using an in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, it was found that the proliferation of rat vibrissae and human hair dermal papilla cells (hDPCs) was significantly enhanced by the COK leaf extract treatment. As determined by quantitative real-time polymerase chain reaction (RT-PCR), the messenger RNA (mRNA) levels of some hair growth–related factors including vascular endothelial growth factor, keratinocyte growth factor (KGF), and transforming growth factor-β2 were found to be higher in the cultured hDPCs exposed to COK leaf extract than those in the untreated control group. In the hair-depilated C57BL/6 mouse model, the stimulation of hair growth was demonstrated in the group of COK leaf extract treatment. Both photographical and histological observations revealed the promotion of the anagen phase in the hair growth cycle by the COK leaf extract in the C57BL/6 mice. Finally, the ultra performance liquid chromatography (UPLC) showed that the COK extract contained mostly cinnamic aldehyde and a small amount of cinnamic acid. The results suggest that the COK leaf extract may find use for the treatment of hair loss.
Preserving Basement Membranes during Detachment of Cultivated Oral Mucosal Epithelial Cell Sheets for the Treatment of Total Bilateral Limbal Stem Cell Deficiency
Authors: Rovere Marie-Rose , Rousselle Patricia , Haftek Marek , Charleux Bruce , Kocaba Viridiana , Auxenfans Céline , Nataf Serge , Damour Odile
Published: April 2018

Total bilateral limbal stem cell deficiency leading to loss of corneal clarity, potential vision loss, pain, photophobia, and keratoplasty failure cannot be treated by autologous limbal transplantation, and allogeneic limbal transplantation requires subsequent immunosuppressive treatment. Cultured autologous oral mucosal epithelial cells have been shown to be safe and effective alternatives. These cells can be transplanted on supports or without support after detachment from the culture dishes. Dispase, known for epidermal sheet detachment, is reported as not usable for oral mucosa. The objective was to find an optimized detachment method providing a sufficiently resistant and adhesive cultured oral mucosal epithelium (COME), which can be grafted without sutures. Enzymatic treatments (dispase or collagenase at different concentrations) were compared to enzyme-free mechanical detachment. Histological immunofluorescence (IF) and Western blotting (WB) were used to examine the impact on adhesion markers (laminin-332, β1-integrin, and type VII collagen) and junctional markers (E-cadherin, P-cadherin). Finally, the COME ability to adhere to the cornea and produce a differentiated epithelium 15 d after grafting onto an ex vivo porcine stroma model were investigated by histology, IF, and transmission electron microscopy. Collagenase at 0.5 mg/mL and dispase at 5 mg/mL were selected for comparative study on adhesive expression marker by IF and WB showed that levels of basement membrane proteins and cell–cell and cell–matrix junction proteins were not significantly different between the 3 detachment methods. Collagenase 0.5 mg/mL was selected for the next step validation because of the better reproducibility, 100% success (vs. 33% with dispase 5 mg/mL). Grafted onto porcine de-epithelialized corneal stroma, collagenase 0.5 mg/mL detached COME were found to adhere, stratify, and continue to ensure renewal of the epithelium. For COME, collagenase 0.5 mg/mL enzymatic detachment was selected and validated on its resistance and adhesive marker expression as well as their anchorage onto our new ex vivo de-epithelialized stroma model.