bluuebunny/crossref_metadata_2025 huggingface dataset:
Transplantation of parathyroid tissue in experimental hypoparathyroidism: in vitro and in vivo function of parathyroid tissue microencapsulated with a novel amitogenic alginate
Authors: Hasse C. , Klöck G. , Zielke A. , Schlosser A. , Barth P. , Zimmermann U. , Rothmund M.
Published: March 2018

Microencapsulation of tissues is an alternative to postoperative immunosuppression in transplantation. In 1994 iso-, allo- and xenotransplantation of microencapsulated parathyroid tissue was achieved in vivo. However, continued analysis of the coating substance (an alginate) determined mitogenic properties. Here, we report on the in vitro and in vivo function of parathyroid tissue microencapsulated with a novel amitogenic alginate suitable for use in humans. To assess in vitro function, parathyroid tissue encapsulated with mitogenic and amitogenic alginate was exposed to rising concentrations of calcium. For in vivo experiments, it was isotransplanted into parathyroidectomized rats. PTH release into medium and PTH serum levels as well as calcium levels of recipient rats were analyzed and compared to native (non-microencapsulated) tissue and empty capsules, respectively. In vivo, transplants were excised and subjected to histologic examination six months after trans-plantation. In vitro, parathyroid tissue encapsulated with amitogenic alginate releases approximately half of the PTH of native tissue, not different from tissue encapsulated with the mitogenic alginate. In vivo, the novel alginate preserved parathyroid function similar to that of native tissue over the six month period resulting in complete reversal of hypoparathyroidism. Correspondingly, histologic examination revealed vital parathyroid tissue in intact microcapsules. By establishing in vitro function and successful long-term transplantation, we have documented the principle of microencapsulation of parathyroid tissue to be effective also with the novel amitogenic alginate, which is suitable for clinical use.
A Partial Dialysate Collection Method
Authors: Cheng Y. L. , Shek C.C. , Wong A.K.W. , Wong F.K.M. , Chau K.F. , Li C.S.
Published: March 2018

This study validates Ing's partial dialysate collection method, which employs proportionate collection using a side tube capped with a small-gauge plastic needle. The urea nitrogen and creatinine levels of the small representative fraction of spent dialysate collected in the above fashion are undistinguishable from those obtained from the total spent dialysate. The estimated urea nitrogen removed during hemodialysis using this approach is similar to that using the total dialysate collection method; Ing's method is simple and useful in quantifying the dialysis dosage and in its assessment of the nutritional status of patients on hemodialysis.
Lipid-Lowering Effects of Fluvastatin in Renal Transplant Patients. A Clinical Observation
Authors: Lal S.M. , Gupta N. , Georgiev O. , Ross G.
Published: March 2018

A Atherosclerosis-related cardiovascular disease remains an important cause of morbidity and mortality in renal transplant patients. We assessed the efficacy and safety of the newer synthetic HMG-CoA reductase inhibitor, fluvastatin, in 12 renal transplant patients who remained hypercholesterolemic, despite having been on the American Heart Association (AHA) Step I diet for 6 weeks. At 8 weeks, compared to the control phase, fluvastatin therapy, 20 mg/day, reduced the total cholesterol (TC) from 321 ± 57 [± SD] to 301 ± 123 mg/dl (p=0.3); low-density lipoprotein cholesterol (LDL-C), from 209 ± 56 to 176 ± 81 mg/dl (p=0.2); and the triglyceride (TG) levels from 343 ± 119 to 277 ± 117 mg/dl (p=0.06); all these changes were statistically insignificant. However, the therapy significantly increased the high-density lipoprotein cholesterol (HDL-C) from 37 ± 11 to 46 ± 13 mg/dl (p=0.006). During this short-term treatment period no adverse biochemical effects were noted with the therapy.
Use of a Catecholamine Sensor in the Control of an Artificial Heart System
Authors: Mabuchi K. , Chinzei T. , Abe Y. , Imanishi K. , Isoyama T. , Matsuura H. , Tago T. , Kouno A. , Ono T. , Imachi K. , Fujimasa I.
Published: March 2018

An electrochemical sensor system to allow real-time measurement and feedback of catecholamine concentrations was developed for use in the control of artificial hearts. Electrochemical analyses were carried out using a carbon fiber working electrode, an Ag-AgCI reference electrode, and a potentiostat. The operating parameters of the pneumatically-driven artificial heart system were altered in accordance with the algorithm for changes in the catecholamine concentration. The minimum detectable concentrations of both adrenaline and noradrenaline in a mock circulatory system using a phosphate-buffered solution were approximately 1-2 ng/ml (10-8 mol/L). An artificial heart control system utilizing this set-up performed satisfactorily without delay, although sensor sensitivity decreased when placed in goat plasma instead of a phosphate-buffered solution, due to the adsorption of various substances such as plasma proteins onto the electrodes. This study demonstrated the future feasibility of a feedback control system for artificial hearts using catecholamine concentrations.
Blood Interaction with a Bioline Heparin Coated HIA-VAD: A Study on Calves
Authors: Van Der Kamp K.W.H.J. , Magielse C.P.E. , Elstrodt J.M. , Van Der Meer J. , Van Oeveren W. , Rakhorst G.
Published: March 2018

The blood compatibility of ventricular assist devices developed by the Helmholtz Institute Aachen (HA-VAD's) was tested on calves. Seven calves received a non-coated HIA-VAD (control) and three a Bioline heparin coated device. The circulatory support of these HIA-VAD's lasted one week. Mechanical blood cell trauma estimated by hematocrit (Hct), hemoglobin (total Hb) and free plasma hemoglobin (free Hb) levels did not differ in either group. All HIA-VAD's in the control group remained thrombus free, except on one occasion when an inflow cannula was obstructed by a thrombus located in the tip. After circulatory support, the animals in this group seemed clinically healthy. However, thrombus formation was observed in the three heparin coated HIA-VAD's. One animal in this group died from complications after re-operation for pneumothorax on the fifth day of support, whereas the other two animals seemed clinically healthy. In these three animals, a stronge decrease in platelet numbers was measured even after 24 hours of support which recovered after 72 hours. This decrease in platelet numbers was associated with a lower degree of platelet aggregation ability stimulated by ADP (p<0.05). Fibrin(ogen) degradation products (FDP) increased significantly immediately after the implantation procedure (p<0.05). Fibrinogen levels initially decreased during the implantation procedure, but increased thereafter in both groups. The FDP levels remained high in this group, although the FDP levels in both groups were decreased after the implantation procedure. The ex vivo measured circulating heparin levels were lower in the heparin coated HIV-VAD group despite the equally administrated heparin doses in both animal groups. No differences were measured in either group with regard to white blood cell (WBC) numbers and complement hemolytic activity (CH50). Despite these hemostatic changes, no mechanical trauma could be demonstrated after seven days of circulatory support.
Use of a Phosphorus-Enriched Dialysate to Hemodialyze Patients with Ethylene Glycol Intoxication
Authors: Chow M.T. , Chen J. , Patel J.S. , Ali S. , Noghnogh A.A. , Leehey D.J. , Ing T.S.
Published: March 2018

A phosphorus-enriched dialysate was used to intensively hemodialyze two non-uremic and non-hyperphosphatemic patients poisoned with ethylene glycol. As a consequence of the use of such a dialysate, we were able to prevent a fall in plasma inorganic phosphorus levels in these patients in spite of the intensive dialytic therapy.
Hemoperfusion with α-Amanitin: An in Vitro Study
Authors: Mydlík M. , Derzsiová K. , Klán J. , Zíma T.
Published: March 2018

The authors carried out sixteen hemoperfusions with α-amanitin in vitro in a closed system using active charcoal, Amberlite XAD-2 and Amberlite XAD-4 in hemoperfusion capsules. As a perfusion solution 4 liters of 0.9% NaCl solution was used. The α-amanitin concentration in the solution was 8.3 ± 0.36 mg/L. Individual hemoperfusion lasted 5 hours. Two hundred and forty minutes of Amberlite XAD-2 hemoperfusion led to the zero values of α-amanitin concentration in 0.9% NaCI solution. When using active charcoal the adsorption capacity of the hemoperfusion capsule was already exhausted at 120 min. The results gathered suggest that the most effective α-amanitin hemoperfusion in vitro was obtained with Amberlite XAD-2 and the least effective with active charcoal. The authors recommend the use of hemoperfusion with Amberlite XAD-2 for acute intoxication with Amanita phalloides in humans up to 24-36 hours after poisoning.
Influence of Acetate and Bicarbonate Hemodialysis on the Plasma Erythropoietin Concentration in Patients with Chronic Renal Failure
Authors: Więcek A. , Franek E. , Kokot F. , Rudka R.
Published: March 2018

The present study aimed to assess the influence of acetate (AC) and bicarbonate (BI) hemodialysis with a cuprophane membrane on plasma erythropoietin (EPO) levels in 30 patients with chronic renal failure (CRF). Fifteen patients were severely anemic with an Hct below 30%, while 13 were moderately anemic with an Hct equal to or more than 30%. None had received rHuEPO or ACE inhibitors before the study. Blood samples for EPO and pO2 estimation were withdrawn before and after 1, 2 and 5 h of AC dialysis. In 11 of the patients with an Hct < 30% the same protocol was repeated during BI dialysis. In spite of a significant decrease in pO2 during the first hour of AC dialysis, the plasma EPO concentration decreased significnatly in both severely and moderately anemic CRF patients from 35.4 ± 2.6 to 23.6 ± 3.5 mU/ml after 5 h of hemodialysis (p = 0.0001 by paired t-test) and from 39.5 ± 8.6 to 27.5 ± 8.9 mil/ml (p < 0.01) respectively. In contrast to AC dialysis, Bi dialysis failed to change the plasma EPO concentration (from 32.3 ± 4.1 to 30.3 ± 4.7mil/ml after 5 h of hemodialysis). Conclusions AC but not BI hemodialysis shows a significant suppressive effect on plasma EPO levels in anemic CRF patients in spite of a significant decline in pO2. Factors other than pO2 seem to be involved in the regulation of EPO secretion in CRF patients during AC dialysis.
A Pivot Bearing-Supported Centrifugal Pump for a Long-Term Assist Heart
Authors: Nakazawa T. , Ohara Y. , Benkowski R. , Makinouchi K. , Takami Y. , Ohtsubo S. , Kawahito K. , Tasai K. , Glueck J. , Noon G.P. , Sueoka A. , Schmallegger H. , Schima H. , Wolner E. , Nosé Y.
Published: March 2018

A pivot bearing-supported centrifugal blood pump has been developed. It is a compact, cost effective, and anti-thrombogenic pump with anatomical compatibility. A preliminary evaluation of five paracorporeal left ventricular assist studies were performed on pre-conditioned bovine (70-100 kg), without cardiopulmonary bypass and aortic cross-clamping. The inflow cannula was inserted into the left ventricle (LV) through the apex and the outflow cannula affixed with a Dacron vascular graft was anastomosed to the descending aorta. All pumps demonstrated trouble free performance over a two-week screening period. Among these five studies, three implantations were subjected for one month system validation studies. All the devices were trouble free for longer than 1 month. (35, 34, and 31 days). After achieving one month studies, all experiments were terminated. There was no evidence of device induced thrombus formation inside the pump. The plasma free hemoglobin levels were within normal ranges throughout all experiments. As a consequence of these studies, a mass production model C1E3 of this pump was fabricated as a short-term assist pump. This pump has a Normalized Index of Hemolysis of 0.0007 mg/100L and the estimated wear life of the impeller bearings is longer than 8 years. The C1E3 will meet the clinical requirements as a cardiopulmonary bypass pump. For the next step, a miniaturized pivot bearing centrifugal blood pump PI-601 has been developed for use as a permanently implantable device after design optimization. The evolution from C1E3 to the PI-601 converts this pivot bearing centrifugal pump as a totally implantable centrifugal pump. A pivot bearing centrifugal pump will become an ideal assist pump for the patients with failing heart.
Immunological Consequences of the use of Xenogeneic Hepatocytes in a Bioartificial Liver for Acute Liver Failure
Authors: Te Velde A.A. , Flendrig L.M. , Ladiges N.C.J.J. , Chamuleau R.A.F.M.
Published: March 2018

The use of cells from xenogeneic origin in a bioartificial liver can have a number of immunological consequences, not only for the cells in the bioartificial liver but also for the patient receiving the bioartificial liver treatment. The impact of these consequences will depend on the immune status of the patient receiving bioartificial liver treatment, the duration and frequency of the treatment and on the extent of interaction between the patients blood (or plasma) and the xenogeneic liver cells. In an experimental model we infused rats with a culture supernatant of pig hepatocytes and demonstrated using Western blots and immunohistological techniques that antibodies are raised against the very small amounts of the pig hepatocyte-derived proteins present in the culture medium. Potential problems of bioartificial liver destruction and the possibility of hypersensitivity reactions due to the secretion of xenogeneic proteins into the circulation of the patient are discussed. Because the liver has an important role in the clearance of immune complexes it is concluded that precautions should be taken when (repeated) application of a xenogeneic bioartificial liver in patients with liver failure is considered.
Effects of Pyruvate-Based or Lactate-Based Peritoneal Dialysis Solutions on Neutrophil Intracellular pH
Authors: Ing T.S. , Zhou X.J. , Yu A.W. , Zhou F.Q. , Vaziri N.D.
Published: March 2018

Acidic (pH 5.2) incubation mixtures containing pyruvate-based or lactate-based peritoneal dialysis solutions (PDSN's) induced comparable degrees of intracellular acidosis in neutrophils. However, addition of an acidic (pH 5.2), pyruvate-based PDSN to a pH-7.4, neutrophil/phosphate-buffered saline mixture brought about higher extracellular and intracellular (neutrophil) pH values when compared to the introduction of an equally acidic, lactate-based PDSN. This poor ability of acidic (pH 5.0-5.5), pyruvate-based PDSN's to resist alkalinizing influences is the cause for the above higher pH values. The higher intracellular pH levels so obtained may be a reason behind why acidic, pyruvate-based PDSN's appear to be more biocompatible than their equally acidic, lactate-based counterparts.
Impact of Spacing Filaments External to Hollow Fibers on Dialysate flow Distribution and Dialyzer Performance
Authors: Ronco C. , Scabardi M. , Goldoni M. , Brendolan A. , Crepaldi C. , La Greca G.
Published: March 2018

A new type of dialyzer (PAN 650 SF Asahi) is analyzed in terms of hydraulic properties, solute clearances and dialysate flow distribution. The new type of dialyzer is a polyacrylonitrile hollow fiber filter, equipped with spacing filaments placed externally to the fibers to facilitate dialysate distribution and avoid channeling. The new filter is compared with a similar filter without spacing filaments. For this purpose, blood and dialysate side clearances have been measured in sequential dialysis session carried out randomly in the same patients. Furthermore, a last generation helical scanner (X-Press / HS1, Toshiba) has been utilized to analyze in vitro the flow distribution of dialysate inside the dialyzer. A contrast medium was injected and a sequence of images has been achieved on a longitudinal section of the dialyzer. This new method permits to avoid any bias due to the cylindrical shape of the dialyzer, since a 10 mm thick rectangular section is analyzed and not the entire body of the filter. The dialyzers equipped with spacing filaments displayed a significant improvement of the dialysate distribution as demonstrated by the radiological pattern. In detail, despite a channeling phenomenon in the peripherical region of the bundle is still present, this is remarkably reduced in comparison with the channelling phenomenon observed in the standard dialyzers. This improved distribution is confirmed by a significant improvement of the solute clearances.
A New in vitro Test Method for Calcification of Bioprosthetic Heart Valves
Authors: Glasmacher B. , Deiwick M. , Reul H. , Knesch H. , Keus D. , Rau G.
Published: March 2018

To investigate the calcification behavior of different bioprosthetic heart valves and verify possible hypotheses of the etiology of valve calcification, an accelerated pulse tester for bioprostheses was developed, whereby up to ten valves can be tested under identical test conditions. Each valve was mounted in a separate compartment on a piston and cyclically moved through a calcifying solution at frequencies of up to 800/min at 37°C. An appropriate calcifying solution was evaluated by incubation tests of bovine and porcine tissue. Calcification was confirmed by measuring Ca and phosphate depletion by atomic absorption spectroscopy, von Kossa staining, EDAX, and microradiography. The first tests were successfully carried out on porcine valves that had been nondestructively assessed for tissue/stress anomalies by holographic interferometry prior to the calcification test. The tests showed that 75% of irregular fringe pattern areas corresponded to the calcification areas.
Erythrothrombocytapheresis and Plasmathrombocytapheresis with Storage in T-sol of Platelets Collected by the New Amicus Cell Separator
Authors: Valbonesi M. , Lercari G. , Florio G. , Carlier P. , Ruzzenenti M.R. , Bruni R. , Magnano E.
Published: March 2018

The Amicus cell separator is the latest apparatus introduced into the international market for high-yield, low WBC contamination and short-procedure time thrombocytapheresis. In its original configuration the apparatus collects platelets for subsequent resuspension in plasma and no collection of PRBC can be carried out along with thrombocytapheresis. In this paper we present the results of plasma-thrombocytapheresis and erythro-thrombocytapheresis after the adaptation of the Amicus to the collection and storage of platelets in a non-plasma medium and the concurrent collection of PRBC. From our study it is concluded that PRBC collection doesn't modify the quality of the platelet product obtained from random donors (platelets pre-count 263×10e3/μl) in terms of yield which is 4.6×10e11 platelets, WBC contamination (1.3×10e5) or procedure time (63±26 min.). The quality of the platelet products is satisfactory too, as measured by aggregation induced by collagen and ristocetin or by the substantial stability of membrane glycoproteins (CD62 - 63 - 51 - 36 - 42B). The concentrate had an average content of 58.8 g of hemoglobin per bag, a final volume of 376 ± 13 ml, (after the addition of 100 ml of SAG-M) and a normal mechanic and osmotic fragility.
Assessment of an Epoxy-Fixed Pericardial Patch with or without Ionically Bound Heparin in a Canine Model
Authors: Chang Y. , Sung H. , Chiu Y. , Lu J.
Published: March 2018

In this study, an epoxy-fixed porcine pericardia I patch with or without ionically bound heparin was evaluated in a canine model as an alternative to the glutaraldehyde-fixed biological patch for clinical applications. To evaluate the effectiveness of this epoxy-fixed patch, a composite membrane composed of: an epoxy-fixed porcine patch with ionically bound heparin; a glutaraldehyde-fixed porcine patch with ionically bound heparin; an ePTFE polymeric patch; a polyester polymeric patch; an epoxy-fixed porcine patch without ionically bound heparin; and a glutaraldehyde-fixed porcine patch without ionically bound heparin was made. This membrane was assessed orthopically in a canine model. The early results (1-4 weeks post implant) revealed that the biological patches with ionically bound heparin had the mildest tissue reactions (inflammatory reaction, fibrosis, and adhesion) among all the test samples. However, by 12 weeks postoperatively, all the test samples had mild to severe tissue reactions. The order of tissue reactions with increasing severity was: the biological patches with ionically bound heparin, the biological patches without ionically bound heparin, and the polymeric patches. The results suggest that heparin may be used to reduce adhesion. Additionally, the epoxy-fixed tissue caused a relatively lower degree of inflammatory reaction than the glutaraldehyde-fixed tissue.
Virtual Extracorporeal Circulation Process
Authors: Boschetti F. , Montevecchi F.M. , Fumero R.
Published: March 2018

Virtual instruments for an extracorporeal circulation (ECC) process were developed to simulate the reactions of a patient to different artificial perfusion conditions. The computer simulation of the patient takes into account the hydraulic, volume, thermal and biochemical phenomena and their interaction with the devices involved in ECC (cannulae dimensions, oxygenator and filter types, pulsatile or continuous pump and thermal exchangers). On the basis of the patient's initialisation data (height, weight, Ht) and perfusion variables (pump flow rate, water temperature, gas flow rate and composition) imposed by the operator, the virtual ECC monitors simulated arterial and venous pressure tracings in real time, along with arterial and venous flow rate tracings, urine production tracing and temperature levels. Oxyhemoglobin arterial and venous blood saturation together with other related variables (pO2, pCO2, pH, HCO3) are also monitored. A drug model which allows the simulation of the effect of vasodilator and diuretic drugs is also implemented. Alarms are provided in order to check which variables (pressure, saturation, pH, urine flow) are out of the expected ranges during the ECC simulation. Consequently the possibility of modifying the control parameters of the virtual devices of the ECC in run-time mode offers an interaction mode between the operator and the virtual environment.
A Novel Field Generator for Magnetic Stimulation in Cell Culture Experiments
Authors: Vogt G. , Schrefl A. , Mitteregger R. , Falkenhagen D.
Published: March 2018

A novel field generator specially designed to examine the influence of low frequency magnetic fields on specific cell material was constructed and characterized. The exposure unit described in this paper consists of a controller unit and three sets of coils. The field generator permits a precious definition of the revelant signal parameters and allows the superposition of alternating current (AC) and direct current (DC) magnetic fields. Critical system parameters were monitored continuously. The three sets of coils, each arranged in the Helmholtz Configuration were characterized. After data processing and visualization the results showed a constant and homogeneous field within the experimental area. The special coil design also allows their use in an incubator.
Pre-Clinical Evaluation of a Novel, Pneumatic, Ventricular Assist Device (Medos® HIA-VAD®) under Pathophysiological Conditions
Authors: Waldenberger F.R. , Meyns B. , Reul H. , Eilers R. , Flameng W.
Published: March 2018

To evaluate a new cardiac assist system, the Medos® HIA-VAD®, we studied the effects of mechanical unloading on regional and global myocardial dysfunction. As a model for the regional temporary contractile dysfunction we chose an anesthetized, open chest preparation in sheep. We occluded the diagonal coronary artery for 15 minutes and reperfused for 90 minutes. Hemodynamic parameters and wall thickening were monitored. Unloading with the 60-ml Medos® HIA-VAD® was performed either during ischemia (group II) or during reperfusion (group III). The recovery of non-uniformity indicated by post-ejection wall thickening was significantly faster (p<0.05) in both groups if compared to the non-assisted group (group I) (all groups n=4). Recovery of systolic wall thickening in the postischemic region in group I was only 76±12%, while it was 103±11% and 92±11% in groups II and III, respectively (p<0.05). In a canine model of global left ventricular failure, we occluded the left anterior descending coronary artery for 20 min, and after 5 minutes of reperfusion, the circumflex artery for 45 min (group I, n=5). After 5 min of CX occlusion in group II we performed assisted circulation for 90 min with the 10-ml (n=5) and the 25-ml (n=5) Medos® HIA-VAD®. In group I, no dog survided, in group II, all survided 4 hours of reperfusion (n=10). Lactate at the end of the experiment was 1.1±0.9 mmol/L (10-ml) and 1.1±0.2 mmol/L (25-ml) (p>0.05 vs. base line). We conclude that the Medos® HIA-VAD® is a reliable assist device that enhances myocardial recovery and allows sufficient peripheral circulation in the case of cardiogenic shock.
Quantitating Dialysis using two Dialysate Samples: A Simple, Practical and Accurate Approach for Evaluating Urea Kinetics
Authors: Raj D.S.C. , Tobe S. , Saiphoo C. , Manuel M.A.
Published: March 2018

Urea kinetics is now widely used to determine the adequacy of dialysis. Several simplified formulae are currently in use but only a few have been accepted into clinical practice because of their simplicity and ease of calculation. A recent analysis of these formulae showed that for the same set of blood urea values the calculated Kt/V can range from 1.0 to 1.5. We have developed a new dialysate-based method (2DSM) to estimate the urea kinetic parameters using dialysate and blood samples taken at the beginning and at the end of dialysis. The total urea removed (TUR) was calculated from the geometric mean of the two dialysate samples, dialysate flow rate and the duration of dialysis. The Watson formula was used to determine the volume of distribution of urea. A comparison of the 2DSM and the direct dialysate quantification (DDQ) method showed the following results (mean ± sd, n = 52): for total urea removal (TUR) 697 ± 32 vs 722 ± 37 mmol (p = 0.6, r2 = 0.928, y = 101 + 0.83 ×, mean difference 25 ± 76 mmol, see Bland-Altman plot), dialysate urea concentration (Durea) 5.55 ± 0.25 vs 5.75 ± 0.29 mmol/l (p = 0.6, r2 = 0.928, y = 0.8 + 0.82 x, mean difference 0.2 ± 0.6 mmol, see Bland-Altman plot), dialyser clearance (K) 232 ± 4.4 vs 235 ± 5.6 ml/min (p - 0.54), Kt/V 1.42 ± 0.04 vs 1.51 ± 0.04 (p = 0.21), volume of distribution of urea (Vd) 40.14 ± 1.04 vs 38.74 ± 1.2 L, (p = 0.38), and PCR 64.6 ± 2.6 vs 68.1 ± 3.1 g/day. We have developed a simple method of determining dialysate-based urea kinetics which requires two dialysate samples, one at the beginning and one at the end of dialysis and a blood sample at the midpoint of dialysis. TUR can be calculated using the dialysate flow rate and the dialysis duration and once this is known all the other kinetic parameters can be calculated.
Dialysis Adequacy of Asian Patients Receiving Small Volume Continuous Ambulatory Peritoneal Dialysis
Authors: Szeto C.C. , Lai K.N. , Yu A.W.Y. , Leung C.B. , Ho K.K.L. , Mak T.W.L. , Li P.K.T. , Lam C.W.K.
Published: March 2018

The usage of three × 2 liter daily exchanges is adopted as the standard CAPD regime in Hong Kong over the last 10 years due to budgetary constraint. This dialysis prescription is considered suboptimal in Western standard. However, the necessity of maintaining Kt/V > 1.7 for CAPD dialysis adequacy is not unanimously agreed. We performed a cross-sectional study of 117 patients on CAPD. Seventy-eight percent of our patients had 3 × 2 liter daily exchange while the rest had 4 daily exchanges. Fifteen percent of patients were diabetic. Patients with Kt/V < 1.7 were similar to those with Kt/V > 1.7 in age, duration of CAPD, BUN, plasma creatinine, albumin, peritonitis rate, and incidence of hypertension. Patients with Kt/V ≥ 1.7 had higher hemoglobin, higher nPCR, more residual renal function; and more of them received 4 daily exchanges. Their peritoneal permeability did not differ. Their employment and rehabilitation status was also similar. Our 5-year survival was 79% despite a lower Kt/V. Notably, the protein catabolic rate of our patients was higher than that in Western patients. This is likely due to dietary difference. Our study suggests small-volume dialysis may be acceptable in Asian population with smaller body size given the financial constraint.
A New Pneumatic Pump for Extracorporeal Circulation: TPP (True Pulsatile Pump). Experimental and First Clinical Results
Authors: Waldenberger F.R. , Vandezande E. , Janssens P. , Morishige N. , Demeyere R. , De Ruyter E. , Wiebalck A. , Flameng W.
Published: March 2018

A pulsatile, membrane type pump, TPP, was developed for use in routine cardiac surgery. The artificial ventricle consists of a polycarbonate housing with an inlet and outlet polyurethane tricuspid valve. The membrane is actuated hydraulically. For pre-clinical studies, we designed a study in sheep. After a pump run of 6 hours the animals were allowed to recover and sacrificed after 72 hours. All clinical parameters returned to normal values (p>0.05 vs. control values). During pump run we found elevated free plasma hemoglobine. However, these values returned to normal until the end of the observation period. Thereafter, the device was used in ten routine cardiac surgery procedures. All patients survived the procedure and were discharged from hospital. The postoperative course of lab parameters (kidney, liver and blood count) was no different to routine cardiac surgical procedures. This pulsatile pump system can thus be safely employed in cardiac surgery.
Influence of Membrane Oxygenators on the Pulsatile flow in Extracorporeal Circuits: An Experimental Analysis
Authors: Inzoli F. , Pennati G. , Mastrantonio F. , Fini M.
Published: March 2018

An experimental analysis was carried out to evaluate the effects induced by two typical extracorporeal circuits on the pressure and flow generated by a roller pump with a pulsatile module. The hydraulic behaviour of the patient was simulated by means of a mechanical mock-up system consisting of a few lumped parameters reproducing the physiologic vascular impedance. Pressure and flow tracings were acquired at different locations along the circuit using an automatic data acquisition system. Nine test conditions with different pulse frequency and systolic time values were examined using a mean volumetric flow rate of approximately 4 l/min. A complete analysis of the results obtained in terms of pressure drops and inflow-outflow differences across the components of the arterial line, as well as the calculation of the hydraulic pulsatile power along the circuit, allowed us to assess the influence of the various components upon the pulsatility. The results indicated that the membrane oxygenators tested slightly affect the pulsatility of the flow and the pressure; on the contrary the arterial pipe line is responsible for large damping and head losses. To optimize the use of pulsatile flow for cardiopulmonary bypass it is necessary to reduce the length of the arterial pipe lines thus integrating the circuit as much as possible.
Uremia, Dialysis and Aluminium
Authors: Di Paolo N. , Masti A. , Comparing I. Barni , Garosi G. , Di Paolo M. , Centini F. , Brardi S. , Monaci G. , Finato V.
Published: March 2018

Few studies have dealt with assaying aluminium levels in different tissues of uremic patients; so far a comparison has never been made between its accumulation in the various tissues of uremic patients and controls. Aluminium levels were determined in the following biological samples: 1)111 serum samples from hemodialysis patients and 55 serum samples from normal subjects; 2) 47 urine samples from the same dialysis patients and 45 from the controls; autopsy tissue specimens (blood, bile, brain, rib, cartilage, cranium, lung, spleen, kidney, aorta, vena cava, liver, muscle) from 12 deceased dialysis patients undergoing post-mortem diagnosis and 10 autopsy cases in which death was not associated with uremia. In living subjects, both serum and urinary levels of aluminium are significantly higher in hemodialysis patients than in controls; a significant positive correlation was found between serum and urinary levels of aluminium. In autopsy specimens, aluminium levels were higher in the dialysis group than controls for all tissues; the differences were statistically significant except in heart and urine. Tissue concentrations of aluminium in the two groups were then analysed separately both in uremic patients and controls. The highest values found in dialysis cases were in the bile, followed by blood, urine and lung; levels in the other tissues were considerably lower. In controls, the distribution was somewhat different, due to much lower levels in the liver and bile with respect to dialysis cases. Again we found surprisingly high levels in the lung. The results show that aluminium storage in uremic patients occurs in all organs and tissues, albeit to different degrees.
Veno-Right Ventricle Bypass as a Lung Support System during Pulmonary Surgery without Ventilation
Authors: Horita K. , Cao Z.L. , Itoh T.
Published: March 2018

A special lung support technique is required during carina! or tracheal surgery. Veno venous extracorporeal membrane oxygenation (ECMO) has become an accepted techinique for temporary lung support. Therefore, the purpose of our experiments was to evaluate the effect of veno venous ECMO (veno-right ventricle bypass) without ventilatory support. In five mongrel dogs, two venous drainage cannula were inserted into the superior vena cava through the right jugular vein and the inferior vena cava through the right femoral vein. In addition, a venous return cannula was inserted into the right ventricle (RV) through the right jugular vein. The veno-right ventricle (veno-RV) bypass system was composed of a centrifugal pump and membrane oxygenator; pump flow was maintained at 88 ± 14 ml/kg/min. Excellent hemodynamics and good oxygenation were obtained. On the basis of these results, we conclude that veno-RV bypass may be used as lung support during pulmonary surgery even though the native lung is not ventilated during the veno-RV bypass procedure.
Effect of a Hybrid Liver Support System on Cardiopulmonary Function in Healthy Pigs
Authors: Janke J. , Gerlach J. , Kardassis D. , Böhmer C. , Rossaint R.
Published: March 2018

The aim of this study was to evaluate the effects of a hybrid liver support system (LSS) on cardiopulmonary function in nine healthy pigs. A hybrid LSS containing primary pig hepatocytes was connected to fully alert animals. The extracorporeal blood flow was maintained between 200-240 ml/min using a roller pump. Continuous plasma flow through the hybrid LSS was 50-60 ml/min. Hemodynamic and pulmonary gas exchange parameters were compared 1 hour before and 1 hour after connection to as well as 1 hour before and 1 hour after disconnection from the hybrid LSS. The hybrid LSS did not influence significantly hemodynamics and pulmonary gas exchange in this group of healthy and awake pigs. It can be concluded that the used LSS did not cause a cardiopulmonary effect per se and should be evaluated further concerning its function as a liver support system in an animal model of acute hepatic failure.
Protein a Carrying PMMA Microbeads: Adsorption of Cholesterol and HlgG from Human Plasma
Authors: Rad A. Y. , Ayhan H. , Pìşkin E.
Published: March 2018

Cholesterol and HlgG adsorbed from human plasma obtained from a hypercholesterolemia patient, onto protein A-immobilized polymethyl-methacrylate uniform microbeads carrying different amounts of protein A (0.264-1.682 mg protein A/g PMMA, or 0.66-4.2 mg protein A/m2 PMMA) were investigated in batchwise experiments. There was no interaction between protein A molecules and cholesterol when cholesterol aqueous solutions were used. However, there was significant cholesterol and HlgG adsorption from the plasma obtained from a patient with hypercholesterolemia. The maximum amounts of cholesterol and HlgG adsorbed were 3.96 μmol cholesterol/g PMMA (5.4 mg cholesterol/g PMMA) and 0.242 μmol IgG/g PMMA (35.4 mg IgG/g PMMA).
Transmural Endothelialization of Vascular Prostheses is Regulated in Vitro by Fibroblast Growth Factor 2 and Heparan-Like Molecule
Authors: Desgranges P. , Barritault D. , Caruelle J.P. , Tardieu M.
Published: March 2018

Endothelialization of vascular prostheses may result from transmural migration of endothelial cells. Angiogenesis is controlled by growth factors like Fibroblast Growth Factor 2 (FGF2) and regulators like heparan-like molecules. To that end, we used heparan-like molecules named RGTA for ReGeneraTing Agent. The RGTA11 used was a chemically derived dextran obtained by successive substitutions with carboxymethyl, benzylamide, and benzylamide sulfonate groups on glucose residues. This agent was further selected for its ability to bind, stabilize and protect FGF2. We defined firstly the angiogenic capability of FGF2 in combination with RGTA 11 on bovine aortic endothelial cells (BAEC) cultured on collagen I gels. Secondly, the role of FGF2 and RGTA 11 in transmural endothelialization was assessed in a three-dimensional in vitro model using a polyethylene terephtalate prosthesis included in collagen gel. BAEC seeded on the external face can migrate to the luminal face of the prosthesis. Microscopic and histological evaluations were performed at 4 and 7 days. Results showed that the addition of RGTA 11 alone did not promote angiogenesis while FGF2 alone did. However, RGTA11 combined with FGF2 produced a significant acceleration in angiogenesis compared to FGF2 alone. This combination magnifies and enhances the angiogenic processes leading to endothelialization of luminal face through transmural cellular migration. Our data demonstrates that in vitro transmural endothelialization of porous vascular prostheses by BAEC cultured on collagen I gels is upregulated by RGTA 11 combined with FGF2.
In Vitro and in Vivo Biocompatibility of Substituted Cellulose and Synthetic Membranes
Authors: Mandolfo S. , Tetta C. , David S. , Gervasio R. , Ognibene D. , Wratten M.L. , Tessore E. , Imbasciati E.
Published: March 2018

Regenerated cellulosic membranes are held as bioincompatible due to their high complement - and leukopenia - inducing properties. Adherence of polymorphonuclear neutrophils and monocyte purified from normal human blood to the three membranes were evaluated in an in vitro recirculation circuit in the presence or absence of fresh, autologous plasma after recirculation in an in vitro circuit using minimodules with each of the three membranes. In in vivo studies, 9 patients were treated with conventional haemodialysis for 2 weeks with each membrane and 1 week for wash-out using haemodialysers with the following surface: 1.95 m2 for benzyl-cellulose, 1.8 m2 for acetate-cellulose and low-flux polysulfone. Measurement of leukopenia, plasma C3a des Arg and elastase-α 1 proteinase inhibitor complex levels as well as urea, creatinine, phosphate and uric acid clearances was performed. Plasma-free neutrophils adhered maximally to acetate-cellulose (65% remaining in the circulation), while there was no significant difference between low-flux polysulfone and benzyl-cellulose (80% circulating neutrophils, at 15 min, p<0.001 vs acetate cellulose). In the presence of fresh plasma, as source of complement, the differences between acetate cellulose vs polysulfone and benzyl-cellulose were even more evident, suggesting the role of complement-activated products in neutrophil adherence. A similar trend was observed for monocyte adherence with the three membranes in the absence or presence of plasma. In vivo studies showed that the nadir of leukopenia was at 15 and 30 min with acetate-cellulose (79%) and benzyl-cellulose (50%) (p<0.05 acetate- vs benzyl-cellulose) and at 15 min with polysulfone (24%) (p<0.01 vs acetate- and benzyl-cellulose). Plasma C3a des Arg levels arose to 2037 ± 120 ng/ml, 1216 + 434 ng/ml and 46 ± 55 ng/ml with acetate-, benzyl-cellulose and polysulfone, respectively. No pre- vs post-dialysis increase in the intracellular content of TNF-α was detected with any of three membranes. Clearance values of urea, creatinine and uric acid were superimposable for all the three membranes. However, benzyl cellulose had a significantly higher clearance for phosphorus (normalized for surface area) (p<0.01 vs acetate-cellulose, 0.001 vs polysulfone). These results implicate that synthetic modification of the cellulose polymer as for the benzyl-cellulose significantly reduces the in vitro adherence, delays the in vivo activation of “classic” biocompatibility parameters and notably improves the removal of inorganic phosphorus.
Variations of Cytokine Levels and Production in CAPD Patients
Authors: Serre A.F. , Marie C. , Beaujon G. , Betail G. , Cavaillon J.M. , Deteix P.
Published: March 2018

Macrophages, predominant cells in dialysates of patients on CAPD without peritonitis, produce a wide variety of substances including cytokines. The aim of this study was to examine the cytokine production in five uninfected patients. This work investigated the presence in dialysates of interleukin-1ß, interleukin-6, interleukin-8, tumor necrosis factor α and the ability of peritoneal macrophages to produce these cytokines. These results were compared with values obtained from control group in non-uremic conditions (peritoneal lavage with isotonic saline or dialysis fluid). All cytokines were detectable in dialysates. Interindividual variations in cytokine concentration in dialysates were wider than variations of production of cytokines ex vivo by stimulated and unstimulated cells. In control group, dialysis fluid inhibited the cytokine production and with isotonic saline, cells produced less cytokines than dialysis patients'cells. The highest levels of interleukin-1 and tumor necrosis factor in dialysates and the highest capacity to respond to LPS were observed in patients having the shortest duration of dialysis. The variability observed did not seem to be due to cells themselves but to their environment.
19 mm Sized Bileaflet Valve Prostheses’ flow Field Investigated by Bidimensional Laser Doppler Anemometry (part I: Velocity Profiles)
Authors: Barbaro V. , Grigioni M. , Daniele C. , D'avenio G. , Boccanera G.
Published: March 2018

The investigation of the flow field downstream of a cardiac valve prosthesis is a well established task. In particular turbulence generation is of interest if damage to blood costituents is to be assessed. Several prosthetic valve flow studies are available in literature but they generally concern large-sized prostheses. The FDA draft guidance requires the study of the maximum Reynolds number conditions for a cardiac valve model to assess the worst case in turbulence by chosing both the minimum valve diameter and a high cardiac output value as protocol set up.

Within the framework of a national research project regarding the characterization of cardiovascular endoprostheses, the Laboratory of Biomedical Engineering is currently conducting an in-depth study of turbulence generated downstream of bileaflet cardiac valves. Four models of 19 mm sized bileaflet valve prostheses, namely St Jude Medical HP, Edwards Tekna, Sorin Bicarbon, and CarboMedics, were studied in aortic position. The prostheses were selected for the nominal annulus diameter reported by the manufacturers without any assessment of the valve sizing method. The hemodynamic function was investigated using a bidimensional LDA system. Results concern velocity profiles during the peak flow systolic phase, at high cardiac output regime, highlighting the different flow field features downstream of the four small-sized cardiac valves.
19 mm Sized Bileaflet Valve Prostheses’ flow Field Investigated by Bidimensional Laser Doppler Anemometry (part II: Maximum Turbulent Shear Stresses)
Authors: Barbaro V. , Grigioni M. , Daniele C. , D'avenio G. , Boccanera G.
Published: March 2018

The investigation of the flow field generated by cardiac valve prostheses is a necessary task to gain knowledge on the possible relationship between turbulence-derived stresses and the hemolytic and thrombogenic complications in patients after valve replacement. The study of turbulence flows downstream of cardiac prostheses, in literature, especially concerns large-sized prostheses with a variable flow regime from very low up to 6 L/min. The Food and Drug Administration draft guidance requires the study of the minimum prosthetic size at a high cardiac output to reach the maximum Reynolds number conditions.

Within the framework of a national research project regarding the characterization of cardiovascular endoprostheses, an in-depth study of turbulence generated downstream of bileaflet cardiac valves is currently under way at the Laboratory of Biomedical Engineering of the Istituto Superiore di Sanità. Four models of 19 mm bileaflet valve prostheses were used: St Jude Medical HP, Edwards Tekna, Sorin Bicarbon, and CarboMedics. The prostheses were selected for the nominal Tissue Annulus Diameter as reported by manufacturers without any assessment of valve sizing method, and were mounted in aortic position. The aortic geometry was scaled for 19 mm prostheses using angiographic data. The turbulence-derived shear stresses were investigated very close to the valve (0.35 D0), using a bidimensional Laser Doppler anemometry system and applying the Principal Stress Analysis.

Results concern typical turbulence quantities during a 50 ms window at peak flow in the systolic phase. Conclusions are drawn regarding the turbulence associated to valve design features, as well as the possible damage to blood constituents.
Grafted Immunoisolated Human Benign Insulinoma Reduces the Incidence of Diabetes in Young NOD Mice without Abolishing the Auto-Immunity
Authors: Fakir M. , Penfornis A. , Elian N. , Cugnenc P.-H. , Altman J.J.
Published: March 2018

Exogenous insulin may prevent the auto-immunity of diabetes in rodents. We studied the preventive effect of a safe endogenous insulin delivery in the diabetes-prone NOD mouse by immuno-protected human insulinoma grafts. Perm-selective macrocapsules seeded with human insulinoma were implanted in 34 young NOD mice, 4 and 8 weeks old. The animals were observed 18 months and compared to 34 NOD mice grafted with empty fibers and 25 simply observed. Before grafting, the capacity of the macrocapsules to release insulin was assessed in vitro by perifusion studies and by implantation to 12 diabetic NOD mice. At perifusion, the insulin release of the macrocapsules responded to step changes in glucose. During the in vivo study, the capsules reduced the glycemia of diabetic mice from 18±3.5 to 7.3±2.1 mmol/L. In the study groups, the survival rate without diabetes (50-70%) was statistically different from controls (10-20%). Recipient's splenocytes transplanted to irradiated male NOD mice transferred the autoimmunity in 75-83% of grafted mice and 86-100% of controls. Insulitis was persistent in all, although milder in the grafted mice. Encapsulated insulinoma prevents diabetes in the NOD mouse without abolishing the auto-immunity. The quantity and quality of the tissues needed and the best moment to graft them have to be determined. The prevention of diabetes by encapsulated pancreatic tissue is appealing because of its simplicity and safety.
Pectin Coated Hollow Fiber Polypropylene Membranes
Authors: Lewińska D. , Piatkiewicz W. , Rosiński S.
Published: March 2018

The aim of this study was to prepare a composite membrane for the selective, extracorporeal removal of human LDL-cholesterol. Pectin coated on a porous polypropylene membrane (PP) was used as an active LDL adsorber. Three types of membrane preparations were performed: coating of native PP, coating after chemical etching and γ-irradiated coated PP. Pectin coated fibers (PCF) were examined under scanning electron microscope (SEM) and tested for hydraulic permeability. As a result of the coating of native and etched PP membrane, pectin layers of various thicknesses (2-16 μm) and porosity were obtained. Irradiation by γ rays gave no insoluble pectin layers.