bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Affecting Npcr in Hemodialysed Patients
Authors: DI Iorio B. , Terracciano V. , Gaudiano G. , Altieri C.
Published: March 2018

The determination of dialysis adequacy is difficult and definitions are in a state of flux (Lindsay). In fact, after fifteen years from the introduction of urea kinetics into clinical practice, nephrologists still do not agree on recognizing the real utility of it. Gotch and Sargent in their mechanistic analysis of the NCDS indicated that the dose of small molecules removal could be defined by Kt/V urea. The results of the NCDS were depicted in a three-variable plot in which six domains could be seen. Several reports have documented malnutrition as being frequently present in patients on maintenance hemodialysis. It is generally accepted that a suboptimal nutritional status is associated with an increased morbidity and may adversely affect rehabilitation and the quality of life. In 1989 Lindsay et al showed that low levels of Kt/V corresponded with low levels of nPCR and found a direct correlation between the two parameters. On this basis, they suggested the hypothesis of nPCR dependence on Kt/V. The Authors showed a good correlation (r=0.73) between nPCR and Kt/V in 55 patients. This work aims to evaluate the correlation between Kt/V and nPCR, real age and dialytic age in a dialytic population in Southern Italy, during a long period of observation (six years, follow up 2,692 months). One hundred and thirty-four patients were studied in six years of observation. Follow up: 2692 months. Twenty-six patients died during the observation period. The simple regression analysis of nPCR vs. Kt/V, real age and dialytic age was performed in 63 anuric patients. nPCR showed a statistical difference (p<0.01) versus reall age, but no difference versus dialytic age and Kt/V. Our research data show that increasing Kt/V administration does not modify the nPCR of patients with initial and steady low protein intake over a medium time of observation. The same happens in patients with initial and steady high protein intake, when decreasing Kt/V administration in a short period of observation. We confirm that nPCR and Kt/V do not show any mathematical correlation in short and medium times of observation. It is also stressed by the simple regression analysis of data for a selected population of anuric uremics on dialysis thrice weekly for long observation times (between three and six years). Variance analysis (in 8 patients who had used all the membranes) showed differences between Kt/V and dialytic age, but not nPCR and real age. Kt/V and biocompatibility do not appear to be correlated directly with nPCR, because other factors are important in determining the general well-being in uremic patients. Such factors have to be considered when prescribing the dialytic “dose” and in clinically evaluating a uremic patient.
Evaluation of Cryopreserved Arteries as Alternative Small Vessel Prostheses
Authors: Nataf P. , Guettier C. , Hadjiisky P. , Lechat P. , Regan M. , Gouezo R. , Gerota J. , Pavie A. , Cabrol C. , Gandjbakhch I.
Published: March 2018

Biologic or synthetic grafts have had limited success in small vessel applications. Studies were initiated to assess the potential use of cryopreserved (CP) arteries as coronary artery bypass conduits. Sheep carotid arteries (internal diameter: 4 mm; length: 10 cm) were cryopreserved in a nutrient media containing 10% DMSO and were stored in a nitrogen vapor at -150°C. After thawing, histological, enzyme-histochemical and functional studies showed slight histological alterations, preservation of enzymal activities and an abolition of the contractile response. In a sheep model, arterial substitution of a 10 cm segment of carotid artery was realised by implantation of fresh autografts (n=4); fresh allografts (n=9) and CP allografts (n=9). After 3 months, all autografts were patent with slight histological alterations. Fresh and CP allografts showed similar modifications: patency rate was 7/9 in both groups. Intimal thickening with cell proliferation was seen in fresh (3/7) and CP (4/8) arteries; loss of smooth muscle medial cells was constant. Adventitia was always involved by a marked inflammatory reaction. One characteristic of CP allografts was the frequent presence of large dystrophic calcifications. In conclusion, morphologic and functional arterial changes occurred after freezing and thawing. In spite of vascular rejection, the patency rate of allografts after 3 months of implantation in arterial circulation remained high and does not seem influenced by cryopreservation.
Efficacy of Lipid Apheresis: Definitions and Influencing Factors
Authors: Bosch T. , Seidel D. , Gurland H. J.
Published: March 2018

The comparison of efficiency of currently available lipid apheresis systems has been hampered by different definitions of efficacy and poorly controlled apheresis conditions. This paper suggests definitions of efficacy and standardization of its determinants. The acute efficacy of risk factor reduction reflects the relative decrease of pathogen by a single treatment session compared to preapheresis levels. Standardization of treated plasma volume in relation to the patients plasma volume and correction of changes in plasma volume during the procedure are mandatory. Its determination is most useful in the technical evaluation of new systems. The long-term efficacy of risk factor reduction as compared to baseline is determined by mean interapheresis levels of e.g. LDL-C in the pseudo-steady-state after about 3 months of regular treatment. It is the major criterion for potential regression of coronary artery disease and absolute average plasma levels of 120 ≤ mg/dl LDL-C should be attained. It is influenced by the acute efficacy of the system, apheresis frequency and rebound kinetics. The clinical efficacy is defined by apheresis induced reduction of coronary morbidity and mortality. It is influenced by long-term risk factor reduction, the selectivity of the system as well as the control of non-lipid risk factors. Apheresis related effects on coronary artery disease comprise functional improvements of hemorheology and vasomotion as well as morphological benefits like regression of luminal narrowing and plaque stabilization. In conclusion, the acute efficacy of apheresis systems should be determined under strictly controlled conditions; however, as apheresis independent factors influence long-term efficacy and, even more so, clinical efficacy of the treatment, differences between the available systems are blurred so that factors like costs and ease of handling may eventually significantly influence the choice of procedure.
Leaching and Corrosion of Polyvinyl Chloride (PVC) Tubes in a Dialysis Water Distribution System
Authors: Cappelli G. , Ballestri M. , Facchini F. , Carletti P. , Lusvarghi E.
Published: March 2018

PVC tubes, from the dialysis water distribution system of a 14 and a 7 year old plant, were analysed by scanner electron microscopy (SEM) and X-ray microanalysis (EDAX). Results showed that the leaching of material occurs depending on time of use. The phenomenon does not modify the chemical composition of the material. Results suggest that PVC alterations, induced by time, could support bacterial proliferation thus reducing the quality of dialysate.
In Vitro Removal of Human Igg by Pseudobiospecific Affinity Membrane Filtration on a Large Scale. A Preliminary Report
Authors: Bueno S.M.A. , Haupt K. , Vijayalakshmi M.A.
Published: March 2018

We have developed a pseudobiospecific affinity membrane device for selective removal of human IgG from plasma or serum in vitro for clinical apheresis application. The pseudobiospecific affinity ligand L-histidine was immobilized through an ether linkage onto poly(ethylenevinyl alcohol) hollow fiber cartridge. The obtained affinity membranes showed high selectivity for IgG adsorption from untreated human serum. These membranes are able to adsorb lgG1, lgG2, lgG3 if Mops buffer is used, and more selectively lgG1 and lgG3 in Tris-HCl buffer. With respect to the binding capacity, the pseudobiospecific affinity membrane used showed a higher capacity as compared to protein A-membranes described in the literature. Due to the high capacity, specificity and stability of the histidine affinity membranes, in addition to their lower cost, the approach proposed in this paper may offer a useful alternative to protein A based devices in the treatment of immune-related diseases.
Biochemical Aspects and Clinical Perspectives of Continuous Urea Monitoring in Plasma Ultrafiltrate: Preliminary Results of a Multicenter Study
Authors: Colasanti G. , Arrigo G. , Santoro A. , Mandolfo S. , Tetta C. , Bucci R. , Spongano M. , Imbasciati E. , Rizza V. , Cianciavicchia D.
Published: March 2018

We tested a new biosensor for urea monitoring in the ultrafiltrate during PFD in a group of 5 hemodialyzed stable patients. The inspection of the UF-urea profile reflects the dynamical changes of the plasma urea concentration during diffusive dialysis and allows the fitting of the main mathematical models of urea kinetics. The biosensor efficiency was 98.4% on average (SD: 1.5%) at Uf fluxes varying from 45 to 55 ml/min (mean: 51 ml/min; SD: 3.2) and at Uf-urea concentrations varying from 23 to 165 mg/dl. The mean difference between Uf-urea determined by the laboratory method and Uf-urea assayed by the biosensor was -1.07 mg/dl and the 95% confidence interval ranged from -2.01 to 0.13 mg/dl. The mean difference between laboratory plasma urea and Uf-urea from the biosensor was on average -1.9 mg/dl and the estimated limits of agreement with a confidence of 95% were -3.16 and 0.64 mg/dl. Comparison between kinetic models and experimental profiles of plasma urea decrease, evaluations of recirculation and post-dialytic rebound, the role of Kt/V on-line during dialysis were the preliminary clinical applications of this biosensor.
Prognosis and Outcome of Neonates Treated Either with Veno-Arterial (VA) or Veno-Venous (VV) ECMO
Authors: Varnholt V. , Lasch P. , Sartoris J. , Koelfen W. , Kachel W. , Lorenz C. , Wirth H.
Published: March 2018

A comparison was done between neonates requiring veno-arterial (VA) ECMO (too small jugular vein, inability to insert a 12 Fr double lumen catheter or cardio-circulatory instability) and neonates treated with veno-venous (VV) ECMO in the same period of time. From 1991-1995 ECMO was done in 48 neonates after failure of maximum conventional treatments, NO-inhalation and HFOV. 30/48 babies were treated with VV-ECMO, with a switch to VA-ECMO later on in 3 of them. In 18 infants VA-ECMO was installed primarily. Differences between the VA- and VV-ECMO group were: the 01 was higher in the VV-treated babies (62±20 vs. 48±13, p < 0.03), as were birth weight (3385±570 vs. 2963±653 g, p< 0.04), gestational age (39.7 ± 1.6 vs. 37.9 ± 2.7 weeks, p< 0.01) and MAP (18.7 ± 2.2 vs. 17.1 ± 2.4 cm H2O, p< 0.05). Severe ICH's occurred more frequently in the VA-treated babies (29 vs. 7%, p< 0.05), the rate of other complications was equal. The mortality rates were 43% (VA) and 15% (VV), p< 0.05. About one third of neonatal ECMO candidates will be treated with VA-ECMO, even if the VV-ECMO technique is available. Need for VA-ECMO implies - due to a higher number of preterm babies and a greater severity of illness before ECMO - a higher incidence of ICH's and a higher mortality rate.
Changes in “Inflammatory” Mediators and Total Body Water during Extra-Corporeal Membrane Oxygenation (ECMO). A Preliminary Study
Authors: Underwood M.J. , Pearson J.A. , Waggoner J. , Lunec J. , Firmin R.K. , Elliot M.J.
Published: March 2018

We studied six patients (5 paediatric, 1 neonate) treated with ECMO to quantify changes in inflammatory mediators (neutrophil elastase (NE), free radical activity (FR), interleukin 8 (IL8)) and total body water (TBW). Blood samples were taken before instigation of ECMO, 4, 12, 24 hours post-ECMO and daily for six days. FR activity was quantified using the oxidised IgG FI/UV ration. NE and IL8 levels were measured by ELISA. TBW was assessed by electrical bioimpedance. Statistical analysis was made using repeated measures analysis of variance and modified t-test where appropriate. Results are presented as mean ± standard error of the mean. FR activity increased 4 hours after instigation of ECMO (IgG FI/UV 32.1 ± 3.2 from 24.1 ± 3.0 p=0.005) and remained elevated. NE also increased by 4 hours (94.8 μg/L ± 8.9 to 678 μg/L ± 153.4, p=0.005) but returned to pre-ECMO values by day 6. IL8 levels rose after ECMO (from 98 pg/ml ± 39, to 24 pg/ml ± 117.4) although no statistical difference was noted over time due to the large variation between subjects (p=0.009). TBW (% pre-ECMO body weight) fell by 24 hours (from 118.6 ± 12.6 to 96.5 ± 8.2 p=0.0004). This study demonstrated that ECMO stimulates an ‘inflammatory’ response to extracorporeal perfusion (increased FR, NE) but despite this, results in a reduction in total body water. The complex relationship between the inflammatory response to prolonged extracorporeal perfusion and its effect on tissue oedema merits further investigation.
Monitoring Sodium Removal and Delivered Dialysis by Conductivity
Authors: Locatelli F. , Di Filippo S. , Manzoni C. , Corti M. , Andrulli S. , Pontoriero G.
Published: March 2018

As cardiovascular stability and the delivery of the prescribed dialysis “dose” seem to be the main factors in determining the morbidity and mortality of hemodialyzer patients today, it is of paramount importance to match hydro-sodium removal with interdialytic load and to verify the delivered dialysis at each session. A specially designed Biofeedback Module (BM - COT Hospal) allows the automatic determination of plasma water conductivity and effective ionic dialysance with no need for blood samples. Using BM, we evaluated the validity of “conductivity kinetic modelling” (CKM) and the possibility that this may substitute “sodium kinetic modelling”. Moreover, we evaluated the “in vivo” relationship between ionic dialysance and effective urea clearance. Our results demonstrate that: 1) CKM makes it possible to obtain programmed end-dialysis plasma water conductivity with an error of less than ± 0.14 mS/cm, roughly equivalent to a sodium concentration of ± 1.4 mEq/L. 2). Ionic dialysance and effective urea clearance are not equivalent but, as the interrelationship between these is known, the BM allows the routine monitoring of delivered dialysis.
Prescription and Surveillance of the Acetate-Free Biofiltration Sessions: The Bicarbonate Cycle
Authors: Pacitti A. , Casino F. G. , Pedrini L. , Santoro A. , Atti M.
Published: March 2018

A computerized system, structured by 4 different models concerning urea depuration, and bicarbonate and sodium handling in acetate-free hemodiafiltration has been conceived for integrated use covering each step of the therapeutic cycle, from a) the prescription of the session to b) its delivery, up to c) the dose - response analysis: the system, now fully developed for the bicarbonate cycle, covers both working areas; the medical one, with a program implemented on a Personal Computer, called Skipper which deals with steps a) and c), and the nursing area, with a program built into the dialytic equipment software. The Skipper program supports the prescription step (a) testing the session schedule by bicarbonate, sodium and urea kinetics. The dialytic equipment, (step(b)) using a different program, on the basis of the scheduled parameters memorizes the end-session plasma bicarbonate level and reacts to any modifications of the parameters regarding blood flow and fluid reinfusion flow suggesting opposite changes in order to reach the scheduled results. Finally (step (c)), the Skipper system statistically evaluates the observed end session bicarbonate plasma level with an expected value with upper and lower confidence bounds obtained by a multiple regression analysis performed on a large population of patients.
Predilution Hemofiltration. Clinical Experience and Removal of Small Molecular Weight Solutes
Authors: David S. , Boström M. , Cambi V.
Published: March 2018

Over 1500 treatments of hemofiltration with on-line preparation of substitution fluid were performed in 16 patients. Two patients were treated for over 40 months. On-line preparation of the solution allowed use of bicarbonate as a buffer. 73-74 L/session were infused in pre-dilution modality, at a rate of about 370 ml/min, and the treatment length was above 4 hrs. The good quality of on-line prepared solution was confirmed by the negativity of microbiological tests and by the absence of clinical or sub-clinical reactions in patients. Urea clearance was calculated by equations considering either plasma flow or whole blood flow. Results were 196-197 ml/min and 186-183 ml/min, respectively. The latter was nearer to the value of directly measured clearance (182-173 ml/min). Kt/V urea was about 1 per session and PCR ranged between 1.3 and 1.4 g/kg/day. A high vascular stability was also observed. Since sodium balance may, at least in part, account for better vascular stability, sodium sieving coefficient was measured during the treatment. The sodium-retaining effect of the increase of protein concentration within the filter, due to the ultrafiltration, was less relevant in pre-dilution hemofiltration if compared to post-dilution hemofiltration. It has been calculated that to obtain a sodium balance similar to that of the hemodialysis (HD), the sodium concentration of infusion solution should be about 2 mEq/L higher than HD dialysis solution. However, difficulty in performing accurate balance studies prevents a general agreement on these conclusions.
Goodpasture's Syndrome Superimposed on Membranous Nephropathy. A Case Report
Authors: Thitiarchakul S. , Lal S.M. , Luger A. , Ross G.
Published: March 2018

We describe a patient with idiopathic membranous glomerulopathy who developed acute deterioration in renal function; this was associated with hemoptysis, severe hypertension, and anti-glomerular basement membrane (anti-GBM) antibody in the serum. Despite aggressive therapy with plasmapheresis, cyclophosphamide and prednisone, the patient progressed to end-stage renal failure and is on maintenance hemodialysis.
Four Years’ Treatment Efficacy of Patients with Severe Hyperlipidemia. Lipid Lowering Drugs versus LDL-Apheresis
Authors: Schiel R. , Bambauer R. , Müller U. A.
Published: March 2018

A total of 47 patients suffering from heterozygous hyperlipidemia were treated with LDL-apheresis (24 patients, aged 49.5±11.5 years), diet and/or lipid-lowering drugs or with diet and lipid-lowering drugs only (23 patients, aged 48.0±11.9 years). After treatment periods of 44.4±14.3 (apheresis group) and 33.5±15.9 (drug group) months, respectively, the ensuing results revealed significant differences (p<0.0001): total cholesterol decreased from 10.4 to 5.5 vs 9.9 to 8.7 mmol/l, LDL from 7.4 to 3.9 vs 6.6 to 5.2 mmol/l, triglycerides from 5.8 to 3.7 vs 4.8 to 4.1 mmol/l and the LDL/HDL-ratio decreased from 7.1 to 3.4 vs 6.7 to 5.8. In the apheresis group one patient died from myocardial infarction vs one non-fatal myocardial infarction and the manifestation of coronary heart disease in three cases in the drug group. There were no severe side-effects in either group. All patients in the apheresis group experienced an increased clinical performance. On the other hand physological well-being of these patients was lower than that of the drug group (scores 42.3±8.9 vs 50.2±9.9, p<0.002). The present trial suggests that a continuing reduction in serum lipid concentrations may lower in a dose dependent manner the risk of development and progression of coronary heart disease. With respect to clinical and laboratory results, LDL-apheresis seems safe and appears to be the most effective therapy.
Techniques for Measurement of Oxygen Consumption Rates of Hepatocytes during Attachment and Post-Attachment
Authors: Smith M. D. , Smirthwaite A. D. , Cairns D. E. , Cousins R. B. , Gaylor J. D.
Published: March 2018

Three techniques for measuring oxygen consumption rate (OCR) of cultured cells relevant to the development of bioartificial liver devices are reported. In an oxystat apparatus, HepG2 cells immobilised on Cytodex 3 microcarriers at a concentration of 106 cells ml-1 had a mean OCR of 0.7 nmol s-1/106 cells. The OCR decreased with increasing cell density, a characteristic previously reported for other cell lines. Rat hepatocytes immobilised on single collagen layers in a flow cell and challenged with ammonia had a mean OCR of 0.59 nmol s-1/106 cells. A novel two-compartment oxystat system was used to determine the OCR of rat hepatocytes during the attachment phase. OCR declined from 1.0 nmol s-1/106 immediately after seeding to 0.7 nmol s-1/106 cells at nine hours. The low OCR for HepG2 reflects loss of certain oxygen dependent metabolic pathways. The OCR measured for rat hepatocytes during and post-attachment are significantly higher than those reported elsewhere and have major implications for the development of bioartificial liver devices.
Low Dose Megestrol Increases Serum Albumin in Malnourished Dialysis Patients
Authors: Lien Y.H. , Ruffenach S.J.
Published: March 2018

To evaluate the efficacy of low dose megestrol on malnourished dialysis patients we treated 16 dialysis patients with persistent hypoalbuminemia (<3.5 gm/dl for 2 consecutive months) and adequate dialysis at a dose of 20 mg orally twice daily. Twelve patients on peritoneal dialysis and 4 on hemodialysis were followed for 4.3 ± 0.6 m (2-11 m). Within one month serum albumin rose from 2.7 ± 0.1 to 3.0 ± 0.2 gm/dl (p<0.05) and remained elevated at the end of follow-up (3.1 ± 0.2, p<0.05 vs. pre-treatment levels). In the 12 responders (increase of albumin >0.3 gm/dl), all of whom reported improved appetite, the maximal increase of serum albumin in 2 months was 0.8 ± 0.1 gm/dl (range: 0.3–1.2). Four patients did not respond (change of albumin: -0.05±0.18, range: -0.6-0.2) because of encephalopathy, amyloidosis, depression or noncompliance. One patient stopped megestrol because of vaginal bleeding from uterine leiomyoma. Three patients died from causes unrelated to the megestrol. Our preliminary study suggestes that low dose megestrol (40 mg per day) increases serum albumin levels in 75% of dialysis patients with malnutrition. It is well tolerated but may cause vaginal bleeding from uterine tumors.
Evaluation of Non-Linear and Linear Mathematical Models for Creatinine and Glucose Fitting in Peritoneal Dialysis
Authors: Amici G.
Published: March 2018

Four non-linear and five linear models for predicting the creatinine dialysate/plasma ratio (CRD/P) and the glucose dialysate/initial concentration ratio (GLD/Do) were evaluated in a group of 31 patients on peritoneal dialysis and subjected to the peritoneal equilibration test (PET 3.86%, 240'). PET results and classification were compared to obtain a definition of patient peritoneal transport characteristics. The monomolecular and rectangular hyperbola non-linear models, the Lineweaver-Burk, Hanes-Woolf and Dadone linear transformations were considered for the CRD/P fitting. A monoexponential and two-exponential decay plus the semilogarithmic transformations were considered for the GLD/Do. These models are simple, accurate and functionally homogeneous. Further studies are advisable however on the individual peritoneal transport classification, since ∼30% of the patients were in different categories for CRD/P and GLD/Do and the fittings do not give better classification results.
Simple Models for Fluid Transport during Peritoneal Dialysis
Authors: Waniewski J. , Heimbürger O. , Werynski A. , Lindholm B.
Published: March 2018

Peritoneal fluid transport can be predicted using different simplified formulas. To evaluate three such models, fluid transport was studied in 38 single six hour dwell studies using standard glucose 1.36% (n=9), 2.27% (n=9) and 3.86% (n=20) dialysis fluids as well as amino acid 2.70% fluid (n=8) in 33 patients on continuous ambulatory peritoneal dialysis (CAPD). Dialysate volume and the peritoneal absorption rate were measured using radioiodinated serum albumin (RISA) as a marker. The dialysate volume over dwell time curves were examined using three mathematical models of fluid transport for solutions with a crystalloid osmotic agent: Model P based on phenomenologically derived exponential function of time (Pyle, 1981), Model OS based on linear relationship between the rate of net volume change, Qv, to the difference of osmolality in dialysate and blood, and Model G based on linear relationship between Qv and the difference of glucose concentration in dialysate and blood. All these models provided a good description of the measured dialysate volume over time curves, however the descriptions with Models OS and G for glucose 3.86% fluid were slightly but significantly less precise. The coefficients of Model OS were stable in time, but the coefficients of Model G and P dependend in general on the time period used for their estimation, especially for glucose 3.86% dialysis fluid. The evaluation of dwell studies with solutions containing amino acid 2.70% (instead of glucose) as osmotic agent, using Model OS and P, showed that the transport coefficients were stable in time and both models provided equally precise descriptions. These results suggested that all three models can be used but models P and OS can be preferred for pratical applications such as predictions of fluid transport with alternative cristalloid osmotic agents. Furthermore, we found that the peritoneal barrier for fluid transport may change transiently during exchanges with the standard glucose - based dialysis fuid, whereas such changes were not observed with the amino acid-based fluid. This discrepancy may be due to a different composition of the dialysis fluids, including osmotic agent, buffer and pH.
A Cross-Over Study of a new Low Molecular Weight Heparin (Logiparin®) in Hemodialysis
Authors: Koutsikos D. , Fourtounas C. , Kapetanaki A. , Dalamanga A. , Tzanatos H. , Agroyannis B. , Kopelias I. , Bosiolis B. , Rammos G. , Bovoleti O. , Sallum G. , Darema M.
Published: March 2018

The safety and effectiveness of a low molecular weight heparin (LMWH) of 4500 ± 1500 Daltons were evaluated in eight hemodialysis (HD) patients, in comparison with unfractionated heparin (UFH). In phase A of the study 3000 ± 500 anti-factor Xa (AFXa) IU of LMWH were administered in bolus for the three consecutive HD sessions of a week. In phase B, 10000 ± 2500 IU of UFH were administered to the same patients for the same time. Were observed no significant differences in hematocrit (Ht), platelets (Pt), fibronogen (FG) and prothrombin time (PT). Whole blood activated coagulation time (WBACT) was more prolonged with LMWH, 24 and 48 hours (start of next session) after administration (p < 0.05), and less prolonged at 5, 60, 120, 180, 240 min compared to UFH (p < 0.001). The activated partial thromboplastin time (APTT) and AFXa activity were more prolonged with UFH at 60 and 240 min (p < 0.001). The clinical effectiveness of the two preparations was similar as judged by thrombus formation and compression time. In conclusion, the present study found no real differences between LMWH and UFH, except for prolongation of WBACT 24 and 48 hours after the administration of LWMH. This probably indicates a cumulative effect of the LMWH and needs further investigation.
The Therapeutic Significance of Pulse Reverse Osmosis
Authors: Prior F.G.R. , Morecroft V. , Gourlay T. , Taylor K.M.
Published: March 2018

Pulse reverse osmosis (1) is a new theory of fluid balance and exchange which suggests that the mean blood pressure and osmotic gradient control fluid balance and that the pulse controls fluid exchange. In vitro testing has confirmed some of the physico chemical principles underlying the theory (2). The hypothesis suggests a relationship between mean capillary blood pressure and osmotic gradient. Imbalance in this relationship can be related to the development of hypertension, hypotension, oedema and shock. In an attempt to test this concept mean blood pressures and colloid osmotic pressures were measured and compared in a group of 50 healthy human volunteers. The results suggest a curvilinear correlation between the mean blood pressure and the COP.
Evaluation of Myoglobin Clearance during Continuous Hemofiltration in a Swine Model of Acute Renal Failure
Authors: Nicolau D.P. , Feng Y.J. , Wu A.H.B. , Bernstein S.P. , Nightingale C.H.
Published: March 2018

Rhabdomyolysis is characterized by extensive damage of striated muscle, while the major complication of this disease is the development of acute myoglobinuric renal failure. Although first described more than five decades ago very little has changed with regard to the management of this entity as conventional hemodialysis has not been shown to effect myoglobin elimination. However, continuous arteriovenous hemofiltration (CAVH) offers an alternative to conventional hemodialysis as this procedure is more effective particularly for removing larger molecular weight substances such as myoglobin. We studied the effect of CAVH on myoglobin clearance in an animal model of acute myoglobinuric renal failure. Swine (n=6) were given 4 grams of equine myoglobin intravenously and underwent the CAVH procedure for six hours each. Once the filtering process was initiated there was a rapid and sustained production of ultrafiltrate. The clearance of myoglobin via the hemofilter was 2.05 ± 1.48 L/day. The amount of myoglobin excreted in the ultrafiltrate over the six hour filtering period was 410 ± 234 mg which accounts for 10.27 ± 5.85 percent of the administered dose. Based on these findings, it appears that the hemofiltration system is a viable option for the removal of myoglobin from the systemic circulation.
In vitro Blood Compatibility Evaluation of Hollow Fibre Membrane Using a Controlled Flow System: A Comparative Study
Authors: Matata B.M. , Yin H.Q. , Courtney J.M. , Gaylor J.D.S. , Lamba N.M.K. , Lowe G.D.O. , Suzuki K. , Kimura H. , Izumi K. , Klinkmann H.
Published: March 2018

A procedure has been established for the in vitro assessment of hollow fibre haemodialysis membranes. A 30 ml syringe containing 20 ml of fresh non-anticoagulated blood was mounted onto a non-pulsatile syringe pump and blood was perfused through minimodules constructed from 80 fibres retrieved from Cuprophan (Baxter ST15), cellulose acetate (M57-12, JMS Co Ltd, Hiroshima, Japan), and AN69HF (Filtral 20, Hospal, France) dialysers. Samples were collected before perfusion, 3, 6, 9 and 12 minutes. The modules were clamped vertically to minimise the effect of red cell pooling and the dialysate compartment was filled with 0.9% saline to minimise ultrafiltration. After sample processing, complement C3a, thrombin-antithrombin III complexes, prothrombin F1 + 2, and factor XII-like activity were evaluated. The results indicated that the system could discriminate between the membranes evaluated and therefore was a relevant procedure for the assessment of hollow fibre haemodialysis membranes.
Development of a Hybrid Liver Support System: A Review
Authors: Gerlach J.C.
Published: March 2018

Hybrid liver support systems (LSS) for the use of the detoxifying, metabolic synthetic and regulatory capabilities of liver cells are under development for extracorporeal therapy of acute liver failure and for bridging to liver transplantation. A summary of our development is discussed. A five-step technique for primary liver cell isolation has been introduced in order to address larger scale procurement of hepatocytes. Immobilisation of the cells after isolation appears to be one of the main factors in maintaining hepatocyte function in vitro. Different techniques have been investigated. Using the cell-cell adhesion technique, a culture model was developed for the immobilisation of hepatocytes between capillary membranes. Four separate capillary membrane systems, each forming independent compartments are woven in order to create a three dimensional network. A bioreactor design has been developed. The construction provides different functions, including decentralised cell perfusion. The bioreactor enables 3 dimensional reorganisation of cells, integral oxygenation and decentralised metabolite exchange. The bioreactor has been scaled-up to allow hepatocytes and sinusoidal endothelial cells to be cultured in quantities sufficient for therapeutic application. In a healthy pig model, possible limiting side effects of therapy with this device were excluded. The efficacy of the system has been demonstrated in a hepatectomised pig model. Subsequently, a complete hybrid liver support system for human studies was introduced and applied clinically.
Importance of the Kinetic Characterization of Liver Cell Metabolic Reactions to the Design of Hybrid Liver Support Devices
Authors: Catapano G. , De Bartolo L.
Published: March 2018

Hybrid liver support devices (HLSDs) developed for the treatment of fulminant hepatic failure often perform well on a laboratory scale but rapidly lose their metabolic functions, or are not therapeutically effective, on a clinical scale. This suggests that the procedures adopted so far for the design of HLSDs are susceptible to improvement. In this paper, we discuss how essential a reliable and thorough kinetic characterization of the liver cell metabolic reactions is to the design of a clinically effective membrane HLSD. The features of the bioreactors used for the kinetic characterization of liver cell reactions are presented and discussed on the basis of the multifactorial nature of such reactions. The relevance of kinetics to the design of a membrane HLSD is also discussed with respect to the effect of the kinetics of oxygen consumption on the performance of the device.
Plasmapheresis in HLA-Immunosensitized Patients Prior to Kidney Transplantation
Authors: Alarabi A. , Backman U. , Wikström B. , Sjöberg O. , Tufveson G.
Published: March 2018

Immunosensitization against the human lymphocyte antigen (HLA) is a problem in most transplant centers. It prolongs the waiting list time in addition to risk of frequent acute rejections. To avoid these problems, various pretransplantation approaches have been attempted e.g. plasmapheresis (PP). The present retrospective study reports our experience with PP in this respect over a 5 year period. Twenty-three chronic hemodialysis patiens with circulating panel reactive antibodies (≥ 50%) and previous kidney graft rejections were treated with 12 PP each. In addition to this, immunosuppression with cyclophosphamide and prednisolone were administered on the first day of PP and after tapering continued until transplantation. HLA-antibodies, as measured by the panel reactive antibodies and the antibody titer, decreased. from about 70% to 30% (p<0.001) and 5 steps of titerdilution, respectively with PP and immunosuppressive drugs; Twenty-two patients were transplanted with cadaveric grafts. Eight grafts were lost due to irreversible rejection, and one due to the patient's death 2 months after transplantation. The cumulative five-year graft survival at the time of follow-up was 59%. Adequate kidney function (serum creatinine mean 150 μmol/l) was observed in all grafts (n=3) still functioning 60 months posttraplant. We conclude that prestransplantation plasmapheresis together with immunosuppressive drugs (cyclophosphamide and prednisolone) is useful in the removal of HLA antibodies in immunized patients awaiting kidney transplantation. It can be considered a valuable approach to increase the chances of successful transplantations.
Artificial Tissues in Perfusion Culture
Authors: Sittinger M. , Schultz O. , Keyszer G. , Minuth W.W. , Burmester G.R.
Published: March 2018

In the stagnant environment of traditional culture dishes it is difficult to generate long term experiments or artificial tissues from human cells. For this reason a perfusion culture system with a stable supply of nutrients was developed. Human chondrocytes were seeded three-dimensionally in resorbable polymer fleeces. The cell-polymer tissues were then mounted in newly developed containers (W. W. Minuth et al, Biotechniques, 1996) and continuously perfused by fresh medium for 40 days. Samples from the effluate were analyzed daily, and the pH of the medium and glucose concentration remained stable during this period. The lactid acid concentration increased from 0,17 mg/ml to 0,35 mg/ml, which was influenced by the degradation of the resorbable polymer fibers used as three dimensional support material for the cells. This perfusion system proved to be reliable especially in long term cultures. Any components in the culture medium of the cells could be monitored without disturbances as caused by manual medium replacement. These results suggest the described perfusion culture system to be a valuable and convenient tool for many applications in tissue engineering, especially in the generation of artificial connective tissue.
A Clinical Study to Assess the Effect of Heparin in Dialyzer Rinsing Solutions
Authors: Opatrný K. , Bouda M. , Kohoutková L. , Vít L. , šefrna F
Published: March 2018

The solution usually recommended for rinsing the blood side, which is an indispensable step in preparing a dialyzer for hemodialysis (HD), contains saline and heparin. The heparin used for rinsing is said to reduce the thrombogenic properties of the dialysis membrane and, hence, also the need for systemic heparinization during the whole procedure. The aim of our study was to establish whether this postulate also applies to polysulphone steam-sterilized dialyzers. To do so, 16 patients on long-term dialysis were randomized into two groups of eight. One group was subsequently treated with polysulphone low-flux dialyzers (F6HPS), the other with polysulphone high-flux dialyzers (F60S). Both groups were examined, in a crossover manner during HD using a dialyzer previously rinsed with 1000 ml of saline plus 2,000 IU of heparin, and during HD using a dialyzer previously rinsed with 500 ml of saline without heparin. Except for the rinsing, HD conditions were completely identical. Blood obtained before HD, and at 15, 60 and 240 min of HD at the dialyzer inlet, was used to determine the activated partial thromboplastin time (to test heparinization control), the thrombin-antithrombin III complex (ELISA, to evaluate coagulation system activation), platelet factor 4 (ELISA, a substance with antiheparin activity), and platelet count. None of the above parameters showed, at any of the collecting intervals, a statistically significant difference between HD with and without heparin with a reduced volume of rinsing solution, or between HD using low- and high-flux dialyzers. It is concluded that heparin used to rinse polysulphone dialyzers before HD has no effect on blood coagulation or on the need for heparin during the procedure.
Numerical Modelling of Blood flow Behaviour in the Valved Catheter of the PUCA-Pump, a LVAD
Authors: Morsink P.L.J. , Verkerke G.J. , Grootenboer H.J. , Mihaylov D. , Rakhorst G.
Published: March 2018

Mechanical heart assistance, performed by the PUIsatile CAtheter (PUCA) pump, chronologically takes place by sucking blood from the left ventricle and ejecting it into the ascending aorta. Within the pump activity the problem of hemolysis and clotting is encountered. In this study the influence of valve geometry on blood cell damage and stagnant zones has been investigated. A variable valve length coupled to a catheter ejection gap and a variable valve angle have been studied. In case of the studied valve, optimal parameter values have been determined. Compared to small catheter ejection gaps with a corresponding valve length, blood damage is found to be less for large ejection gaps with corresponding valve dimensions. In systole a valve positioned in a 0° angle proves to be best, whereas in diastole a +20° angle is preferable. Because the system is operating in both systole and diastole, a 0° angle valve is applied.
External Biodegradable Supporting Conduit Protects Endothelium in Vein Graft in Arterial Interposition
Authors: Bambang L.S. , Moczar M. , Lecerf L. , Loisance D.
Published: March 2018

The prevention of circumferential distension could reduce structural damage in arteriovenous grafts. We studied the effect of an external biodegradable supporting conduit on the endothelium and extracellular matrix in vein graft in a pig model. Cephalic vein control grafts (Group I) and jugular veins wrapped in a vicryl mesh tube (I.D. 4mm) (Group II) were implanted into autologous carotid arteries (n=14). The grafts were explanted after 1 and 24 hours and at 1 and 3 weeks and evaluated by ELISA for endothelial DNA synthesis and by immunohistoenzymic assays for cells and extracellular matrix. In group I an initial loss of endothelial and smooth muscle cells along with elastin breakdown was followed by an impaired endothelial regeneration and significant graft wall thickening. The elastic tissue was replaced by collagen type I and chondroitin sulfate accumulations, which included a disarray of α-smooth muscle actin positive cells. The endothelium was preserved in group II. After 3 weeks the circumferential elastin layers were densified, distended and separated from the endothelium by a neointimal growth of irregular thickness. Biodegradable perivenous conduit minimized endothelial injury and allowed the partial preservation of elastin fibers and smooth muscle cells in the arteriovenous graft. It did not however, prevent myofibroblastic cell proliferation and triggered a macrophagic reaction.
In Vivo Testing of a Magnetically Suspended Centrifugal Pump Designed for Long-Term Use
Authors: Yamada T. , Nishimura K. , Akamatsu T. , Tsukiya T. , Park C.H. , Kono S. , Matsuda K. , Ban T.
Published: March 2018

The life of currently-available centrifugal pumps is limited to no more than three days. As a magnetically suspended centrifugal pump (MSCP) contains no shaft or seal, it could be expected to have a longer life expectancy. The MSCP was evaluated in a chronic animal model using eight adult sheep. Left ventricular assist with the MSCP was instituted between the left atrium and the descending aorta. The flow rates ranged from 2.5 to 6.0 L/min. The duration of the experiments ranged from 14 to 60 days. No mechanical failure occurred. The plasma free hemoglobin levels remained within an acceptable range (3-19 mg/dL). No reduction in the counts of red blood cells or platelets was observed. Thrombus formation within the MSCP was recognized in one pump. The main reason for termination was thromboembolism derived from the circuits. Three types of regulation methods (constant rotational speed, constant motor current, and controlled motor current) were also investigated. Regulation by a constant motor current mode altered the pressure-flow (P-Q) characteristics, and thereby, a steadier pump flow was obtained compared with regulation in the constant rotational speed mode. Moreover, the controlled motor current mode can change the P-Q relationship. These results demonstrate that the MSCP is a promising device for long-term use.
Haemodynamic Alteration in Patients Undergoing Chronic Haemodialysis
Authors: Costantino M. L. , Cairo G. , Fumero R.
Published: March 2018

Fifteen elderly patients, 13 of them undergoing chronic haemodialysis, 1 acute and 1 coming from Continuous Ambulatory Peritoneal Dialysis (CAPD) either with no significant cardiovascular alteration or presenting various cardiovascular pathologies were studied to investigate the possibility of onset of hypotensive episodes during dialytic treatment depending on cardiac or vascular alteration in the patients. Monitoring of the arterial pressure on the contralateral arm and on the lower limbs by using the Takeda System, made it possible to compute the Windsor Index (WI). The figures obtained were correlated to the Ejection Fraction Index (EFI) to investigate the relation between WI alteration and haemodynamic variations in the patient. The results show that cardiothoracic recirculation is much more present in those patients with pathologies that affect EFI which worsens during dialysis due to the loss of fluid. Moreover the results obtained from the two patients with temporary access and no evident cardiovascular pathology show the constancy of the haemodynamic parameters throughout the dialytic treatment.
Immunoisolation of Hybrid Liver Support Systems by Semipermeable Membranes
Authors: Gleißner M. , Bornemann R. , Stemerowicz R. , Meißler M. , Neuhaus P. , Gerlach J.C.
Published: March 2018

Immunoisolation of hybrid liver support systems (LSS) utilizing suitable semipermeable membranes as an immune barrier enables neither immunocompetent cytotoxic factors to cause damage to the hepatocytes in the bioreactor nor xenogenic hepatocyte products to cause immunological side effects in patients. To determine the capability of membranes as an immune barrier, 6 flat membranes were investigated: Cuprophan (C-100), cut-off MW 1000, Cuprophan (C-240), cut-off MW 10,000, Polypropylen hydrophilic and hydrophobic (PPhi, PPho), cut-off MW 500,000-1,000,000, Polysulfon (PS), cut-off MW 1,000,000, Polyamid (PA), cut-off beyond MW 1,000,000. The permeability of the membranes to plasma factors and liver protein fractions (LP) was studied by routine biochemical methods and gel electrophoresis. In a second study, pigs (n=7) were immunised by LP after membrane passage. The results showed PA, PS, and PPhi to be completely permeable for plasma factors and LP, C-100 and C-240 for urophanic substances, and C-240 again for LP under MW 14.000. All 7 pig sera studied by Western blot discovered pre-formed xenoreactive natural IgG-antibodies (NAB) against human liver antigen (AG) with MW 26.000. AB de-novo-synthesis was demonstrated for AG with MW 45.000. No AB-synthesis was induced for epitopes under MW 26,000. These results suggest that limiting the cut-off of bioreactor outflow membranes to MW < 26,000 could avoid immunological side effects to patients.
Comparison of Two Methods of Pancreas Islets Immunoisolation
Authors: Orłowski T. , Sitarek E. , Tatarkiewicz K. , Sabat M. , Antosiak M.
Published: March 2018

The efficacy of two methods of Langerhans islets immunoisolation was compared. For this purpose the function of islets encapsulated with alginate/polyethylenimine/protamine/heparin (APPH) or with alginate/poly-L-lisine/alginate (APA) membranes was assessed: in vitro according to their survival and response to glucose challenges, and in vivo according to their capability to provide sufficient insulin delivery to maintain normal fasting blood glucose following xenotransplantation to streptozotocin diabetic mice. In vitro insulin secretion and the response to glucose challenge of APPH and APA encapsulated islets were comparable to free islets. In vivo intraperitoneal concordant xenotransplantation of APA encapsulated rat islets reversed the diabetic state of streptozotocin diabetic mice for a longer period, than APPH islet grafts. This study clearly demonstrated the inadequacy of in vitro methods in the prediction of in vivo results of islets transplantation.
Dynamically vulcanized high-density polyethylene/nitrile butadiene rubber blends compatibilized by chlorinated polyethylene
Authors: Zhang Lin , Wang Libin , Shi Yujiao , Wang Zhaobo
Published: March 2018

Thermoplastic vulcanizates (TPVs) based on high-density polyethylene (HDPE)/nitrile butadiene rubber (NBR) blends were prepared by dynamic vulcanization where chlorinated polyethylene (CPE) was used as a compatibilizer. The effects of CPE on mechanical properties, Mullins effect, dynamic mechanical properties, and morphology of the blends were investigated systematically. Experimental results indicated that CPE had an excellent compatibilization on the HDPE/NBR blends. Dynamic mechanical analysis studies showed that the glass transition temperature of NBR phase was slightly shifted toward higher temperature with the CPE incorporation, leading to the increasing interface compatibility. Mullins effect results showed that the compatibilized HDPE/NBR blend had relatively lower residual deformation and internal friction than that of HDPE/NBR blend, indicating the improvement of elasticity. Morphology studies showed that the size of the NBR particles was decreased with the existence of CPE; moreover, the fracture surface of HDPE/CPE/NBR TPV was relatively smoother than that of HDPE/NBR blend.