bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of the Anemia of Hemodialysis Patients with Recombinant Human Erythropoietin
Authors: Schaefer R.M. , Kuerner B. , Zech M. , Denninger G. , Borneff C. , Heidland A.
Published: April 2018

Fifteen long-term hemodialysis patients suffering from stable anemia received recombinant human erytheropoietin (r-huEPO). The hormone was given intravenously at the end of each dialysis session starting with a dose of 24 IU/kg. This dose was doubled when hemoglobin levels did not rise within 2 weeks. The number of reticulocytes started to increase after 14 days of treatment. The hematocrit rose from baseline values of 23.7 ± 1.2% to 32.4 ± 1.3% after 24 weeks of treatment. In parallel, hemoglobin values increased from 7.3 ± 0.3 g/100 ml to 10.1 ± 0.4 g/100 ml. As for side effects, 3 patients developed hypertension and 2 patients suffered from occlusions of their arterio-venous fistulas. There was no evidence of major organ dysfunctions, toxic effects, allergic reactions, or antibody formation. These data show that rHuEPO is able to correct the anemia of patients undergoing hemodialysis treatment.
Design Considerations for a Small Bore Vascular Prosthesis
Authors: Underwood C.J. , Tait W.F. , Charlesworth D.
Published: April 2018

No synthetic prosthesis has yet been found which can satisfactorily be used as a substitute for saphenous veins in vascular surgery. One explanation for the lack of success is that their properties and behaviour do not mimic those of the arteries they replace. The essential features for a successful vascular prosthesis, over and above biocompatibility, are a low friction non-thrombogenic flow surface, mechanical (elastic) behaviour that matches natural artery and dimensions that approximate the host vessels. This will allow a high velocity of flow with low impedance. A prosthesis with this specification would avoid the problems of flow disturbances and reflection at the anastomoses, pulse wave damping and large pressure gradients, all of which reduce pulsatile energy.

We have designed a vascular prosthesis based upon the above criteria. It has an internal diameter of 4 mm and a wall thickness of 1 mm. Its geometry makes it kink resistant and a good match for tibial and coronary arteries. The prosthesis is made from Polyurethane and its mechanical properties, which approximate to those of peripheral arteries, are achieved via a mechanism of internal wall compression rather than external circumferential expansion.

To assess the in-vivo potential of this prosthesis, 21 grafts were implanted in 11 sheep, replacing a section of carotid artery with a 6 cm long prosthesis. All 21 grafts were patent after 3 months. One graft was removed for histological examination. 16 of the remaining 20 grafts were patent after 7 months. Problems associated with thrombosis were not encountered and we conclude that this prosthesis shows good potential as a small bore vascular substitute.
Three-Dimensional Visualization of Velocity Profiles in the Ascending Aorta in Humans.
Authors: Paulsen P.K. , Hasenkam J.M. , Stødkilde-Jørgensen H. , Albrechtsen O.
Published: April 2018

Blood velocities were recorded intraoperatively in the ascending aorta approximately 6 cm downstream of the aortic annulus in eight patients with normal aortic valves (prior to coronary bypass surgery) and in seven patients after implantation of a St. Jude Medical valve (4) or Starr-Edwards Silastic Ball valve (3) in the aortic position by means of constant temperature hot-film anemometry. The velocities were measured during 5-15 heart cycles at 41 predetermined measurement points almost evenly distributed in the cross sectional area. Velocity profiles were visualized three-dimensionally at 100 time intervals during one mean heart cycle. The standard deviation of velocities was correspondingly three-dimensionally visualized. For the patients with normal aortic valves the velocity profiles were generally flat but skew, with the highest velocity closer to the left vessel wall at the start of systole. During systole the skewness turned counterclockwise with the highest velocities closer to the posterior, right and finally anterior vessel wall at the end of systole. In patients with an artificial heart valve in the aortic position the design of the valve was reflected on the contour of the profiles. The findings correspond well with model studies.
Analysis of Velocity in the Ascending Aorta in Humans.
Authors: Paulsen P.K. , Nygaard H. , Hasenkam J.M. , Gormsen J. , Stødkilde-Jørgensen H. , Albrechtsen O.
Published: April 2018

To analyze velocity spectral energy distribution in humans, blood velocities were recorded by means of hot-film anemometry at 41 predetermined measurement points in the cross-sectional area of the ascending aorta approximately 6 cm downstream of the aortic valves. Measurements were made in 8 patients with normal aortic valves, in 4 after insertion of a St. Jude Medical (SJM) aortic valve and in 3 after insertion of a Starr-Edwards Silastic Ball (SSB) aortic valve. Data analysis based on Fast Fourier Transform demonstrated that turbulence energy was lower in patients with normal aortic valves than in patients after insertion of an artificial valve in the aortic position and probably more pronounced after SSB valves than after SJM valves. The spatial distribution of the turbulence energy above 100 Hz was more irregular than corresponding laminar velocities previously presented. The Ver100 (Velocity Energy Ratio at 100 Hz, i.e. the velocity energy above 100 Hz divided by the total velocity energy) proved useful for evaluating differences in flow disturbances downstream of different aortic valves. The mean VER100 in the three categories of patients were respectively 0.3, 1.4, and 2.1%.
Morbidity in Valvular Heart Replacement: Risk Factors of Systemic Emboli and Thrombotic Obstruction
Authors: Abdelnoor M. , Hall K.V. , Nitter-Hauge S. , Rostad H. , Risum Ø.
Published: April 2018

A study on a cohort of 839 patients with valvular heart replacement between June 1977 and May 1985 showed that the linearized rates of systemic emboli and thrombotic obstruction were 1.4/100 pts/year for Aortic Valve Replacement (AVR), 2.2/100 pts./year for Mitral Valve Replacement, and 3.00/100 pts./year for Double Valve Replacement (DVR).

The 5-year free-from-thromboembolism (TE) survival was 95% for AVR and 92% for MVR. The hazard function (the instantaneous risk) for TE peaked in the first six months after operation for AVR and MVR.

Another analysis using the Cox regression model to estimate risk factors of systemic emboli and thrombotic obstruction pinpointed two factors in the AVR group: presence of aortic regurgitation (AR) and age at operation. In the MVR group the sole predictor covariate was sex of the patients, with a higher hazard for females. Our results underline the importance of patient-related factors besides the type of prosthesis as predictors of morbidity from TE.
Plasma Concentrations of Atrial Natriuretic Peptide, Arginine Vasopressin and Hormones of the Renin-Angiotensin System in Patients with End-Stage Renal Disease
Authors: Elias A.N. , Vaziri N.D. , Pandian M.R. , Kaupke J.
Published: April 2018

Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), plasma renin activity (PRA) and aldosterone, were measured before and after 3 h of hemodialysis in 9 patients with end-stage renal disease on maintenance hemodialysis. Hormone concentrations were also determined in the same patients on a separate occasion after 1 h of ultrafiltration (UF). Plasma concentrations of ANP were significantly higher in the patients with ESRD than in a normal reference population and declined after both 1 h and 3 h of hemodialysis. Plasma concentrations of ANP failed to exhibit a significant decline after 1 h of UF. Plasma AVP concentrations were not significantly different after either hemodialysis or UF, while plasma aldosterone concentrations fell with hemodialysis. The decline in plasma aldosterone concentrations paralleled the decrease in dialysis-induced fall in serum potassium concentrations. There was no correlation between the blood pressures, heart rate, interdialytic weight gain and estimated fluid overload and any of the hormones measured except for the plasma renin activity (PRA) which correlated significantly with the systolic blood pressure. The data suggest that ANP may not be a major factor in blood pressure regulation in normotensive patients with ESRD and its elevation in patients with ESRD is most likely due to fluid overload and atrial distention as well as a possible reduction in its metabolic clearance in renal insufficiency. The fall in plasma ANP following hemodialysis is not due to its removal by dialysis but is most likely due to a reduction in ANP production caused by dialysis-induced correction of hypervolemia.
Red Blood Cell Volume Distribution Width (RDW) in Uraemic Patients on Chronic Haemodialysis
Authors: Docci D. , Delvecchio C. , Gollini C. , Turci F. , Baldrati L. , Gilli P.
Published: April 2018

Red blood cell volume distribution width (RDW) was obtained with the Coulter counter in 60 haemodialysis patients and 55 normal individuals. RDW tended to be higher in the former and the degree of increase was to some extent correlated with the underlying nephropathy. Although RDW failed to correlate with conventional tests of iron status, it was observed that iron administration could produce a decrease toward normal in RDW and a parallel increase in haemoglobin when the initial RDW was increased. In contrast, the response to iron was negligible in the patients with normal RDW basally. It was concluded that high RDW is an acceptable indicator of iron deficiency in haemodialysis patients.
The Surface Composition of Commercial Polyester Arterial Prostheses - An XPS Study
Authors: Paynter R. W. , King M. W. , Guidoin R. G. , Rao T.
Published: April 2018

The importance of identifying and quantifying the level of contaminants on the surface of biomaterials has long been recognized as a significant step towards predicting the biocompatibility and rate of healing of implantable devices. Yet suitable techniques for characterizing the surface chemistry of soft and flexible biomaterials with an uneven surface contour such as those used in vascular prostheses have only recently been made available. As a first step towards determining the effect of surface contaminants on the healing behaviour of vascular prostheses, this study used X-ray photoelectron spectroscopy (XPS) to characterize the surface chemistry of 14 virgin polyester arterial prostheses from a wide variety of sources. Generally speaking, all surfaces appeared relatively clean. However, the results indicate that certain prostheses were not manufactured with Dacrorf-like fibres, and that some exhibit significantly carbon-rich surfaces. This suggests that the surface of these devices has been modified either by a hydrocarbon lubricant or by vapour phase hydrocarbons during fabrication.
Technical Evaluation of Newly-Developed Inorganic Membranes for Plasma Fractionation
Authors: Ozawa K. , Ohashi K. , Ide T. , Sakai K.
Published: April 2018

Constant transmembrane pressure experiments were made by crossflow filtration to clarify sieving characteristics of microporous glass membranes for plasma fractionation. The distribution of pore diameters is more limited in the microporous glass membranes than in currently utilized synthetic polymer membranes. The filtration resistance of the concentration polarization layer is the dominant factor in plasma fractionation. Proteins are separated more sharply with a higher wall shear rate because of destruction of the concentration polarization layer formed on membrane surfaces. Plasma fractionation using a microporous glass membrane with a pore diameter of 15 nm may allow separation of albumin and IgG at higher wall shear rates. Cascade filtration techniques using microporous glass membranes with various pore diameters may be suitable for plasma fractionation.
Peritoneal dialysis as therapy for electrolyte and acid base disorders
Authors: Inagaki Y. , Miyazaki T. , Amano I.
Published: April 2018

Peritoneal dialysis (PD) does not demand special equipment and its fluid composition can be easily changed according to the individual condition. Nine patients with chronic or acute renal failure presented severe metabolic alkalosis (MA). Hemodialysis (HD) proved virtually ineffective and the MA persisted. Physiological saline solution was adopted as the main component of the PD fluid for the treament of MA. By this method, CI– can be shifted from PD fluid to extracellular fluid (ECF) and HCO3– from ECF to PD fluid by ionic gradient. Therefore, pH and base excess (BE) of these patients both improved to the normal range after several fluid exchanges. The lowering effect of BE (ΔBE/L) ranged from 0.99 to 2.6. Hyposaline and normo-osmol solution (Na+ 70 mEq/L) were used for one patient with hypernatremia and consciousness disturbance. Serum (S)-Na decreased from 170 to 138 mEq/L, and consciousness became almost clear with the use of 15 L of PD fluid. Hypersaline solution (Na+ 190 mEq/L) was used for two patients with hyponatremia (S-Na 113 and 121 mEq/L). S-Na rose to within the normal range after 16 and 9 L in the two cases. A fluid mixed with distilled water, 10% NaCl and 7% NaHCO3 (HCO3– 34 - 68 mEq/L) was used to treat lactic acidosis in two patients. By this method, HCO3– can be shifted from PD fluid to ECF and lactic acid from ECF to PD fluid. Two patients recovered from prolonged shock, and pH was corrected by 10 L and 4 L, respectively. PD should be considered for application in other diseases besides renal failure.
The Production of Platelet-Activating Factor during Hemodialysis
Authors: Tetta C. , Segoloni G. , Pacitti A. , Regis G. , Salomone M. , Turello E. , Camussi G. , Vercellone A.
Published: April 2018

Regenerated cellulosic membranes (CU) induced the aggregation of plasma-free human neutrophils when recirculated in a dynamic model of dialysis without the patient on the circuit. Neutrophil aggregation was linked to the production of PAF by these cells. In the absence of detectable PAF production, no neutrophil aggregation occurred, as observed during recirculation with polymethylmethacrylate (PMMA) membranes. With polycarbonate (PC), PAF production and aggregation of neutrophils were both almost half the values with CU. PAF production was studied in ten hemodialysis (HD) patients tested twice with CU and once with PC and PMMA membranes. PAF was extracted in the venous blood during filling of the dialyser for 9/20 of patients with CU (3.1 ± 2.9 ng/ml, mean ± 1 S.D.) a membrane that induced marked leukopenia (> 50% of basal values at 15 min), C3a des Arg generation (> 500% at 5 min), and plasma levels of the elastase-alpha1-proteinase inhibitor complex (> 500% at the end of HD). Membranes such as PC and PMMA showing intermediate or low potential to induce leukopenia and C3a des Arg generation, respectively, did not trigger the production and release of PAF in detectable amounts at any interval. However, with PMMA, plasma neutrophil elastase was significantly higher than baseline at the end of dialysis. These levels were not significantly different (p < 0.05) from those observed with CU and PC membranes
Regulation of Plasma Aldosterone during Hemodialysis
Authors: Krämer B.K. , Ulshöfer T.M. , Müller G.A. , Ress K.M. , Risler T.
Published: April 2018

In order to clarify the influence of serum potassium, serum sodium and plasma angiotensin II concentrations on aldosterone release during hemodialysis (HD), six chronic hemodialysis patients were studied during HD with varying dialysate sodium concentrations and different buffers. Plasma aldosterone concentrations were higher during acetate than bicarbonate HD, during low sodium compared to high sodium HD, and were correlated inversely to serum sodium concentrations. The decline in plasma aldosterone concentrations during HD paralleled the decrease in serum potassium concentrations, and plasma aldosterone concentrations were correlated with serum potassium concentrations. In addition, plasma aldosterone and plasma angiotensin II concentrations were correlated significantly. It is proposed that serum potassium and the renin-angiotensin system are the main factors of aldosterone release during hemodialysis, while serum sodium per se seems to be of less importance. The dialysate buffer employed also plays a role in aldosterone regulation (via the renin-angiotensin system)
Short Time Dialysis with Continuous Blood Volume Control
Authors: Stiller S. , Schallenberg U. , Gladziwa U. , Ernst E. , Mann H.
Published: April 2018

Continuous measurement of haemoglobin concentration is used to control changes of blood volume during haemodialysis. Ultrafiltration is either kept constant throughout the session or after starting with a rate (1.5 to 2 l/h), is manually controlled in order to limit blood volume reduction to a preset percentage. Ultrafiltration is step-wise decreased (a) or switched on and off (b) accordingly. Blood volume decrease with constant ultrafiltration is compared with method (a) and (b) in 4 stable haemodialysis patients. Constant ultrafiltration rate and the same total amount of ultrafiltrate causes a nearly 3% (mean) greater volume reduction as compared with method (a) and (b). No difference was observed in blood pressure and heart rate. We conclude that ultrafiltration in stable haemodialysis patients can be completed in short time without consequences for cardiovascular stability.
Curve of Perceptive Intellectual Deterioration in Hemodialysis Patients
Authors: Ventura M.C. , González R. , Alarcon A. , Morey A. , Bestard J. , Toran D. , Marco J.
Published: April 2018

In order to optimize the results of kidney transplant, i.e. patient's acceptance and speedy recovery, the available organ resources must be combined with appropriate “preparation” of the patient's mental state. In order to plot the “mental deterioration curve” of patients on a hemodialysis program, the present study was made on 62 patients in a general hospital in Spain. The possible repercussions of treatment of kidney disease on intellectual (Weschler's Adult Intelligence Scale-WAIS test) and perceptive (Benton test) capacity were investigated. Samples were grouped according to whether they had been on dialysis for up to four years (<4) or more than four years (>4). The WAIS test for the >4 group indicated a lower I.Q. These results indicated that it was after four years on dialysis that greater negative effects began to be seen in perceptive-intellectual capacity. The Benton test indicated that time on hemodialysis adversely affected the patient's capacities. A sharp decline was seen particularly between two and four years in the <4 group, suggesting that patients’ mental conditions vary with time on dialysis but that their resources and capacities are still fairly untroubled by the treatment in the first two years. In the light of these findings, the deterioration curve should be taken into account when planning kidney transplant, in order to take advantage of the initial period if possible.
Complement Activated Leucopenia during Hemodialysis: Effect of Pulse Methyl-prednisolone
Authors: Enia G. , Catalano C. , Misefari V. , Salnitro F. , Mundo N. , Tetta C. , Maggiore Q.
Published: April 2018

We tested in vivo the effect of methyl-prednisolone (MP) on C5a release and granulocytopenia occurring early in the course of extracorporeal blood circulation through a Cuprophan dialyzer. MP boluses (30 mg/kg) were given to 10 consenting patients suffering from acute renal failure, immediately before blood started to circulate through a hollow-fiber Cuprophan dialyzer. To avoid drug loss through the dialyzer membrane, dialysate flow was witheld during the first hour of treatment and ultrafiltration was kept near zero (sham dialysis). Control procedures were carried out in a similar way, without MP. MP concentration, differential WBC count and anaphylotoxin C5a were serially measured during the procedures. MP pharmacokinetics was evaluated in six other uremic patients off dialysis. As shown by similar C5a levels in dialyzer effluent blood, complement cascade was activated by Cuprophan to a comparable degree whether or not patients received MP. Neutrophil count dropped 68% during the control procedure and 54% during sham dialysis preceded by MP (95% confidence interval of the difference, 1.97–27.2). Sham dialysis did not apparently influence serum MP levels, as shown by similar peak values in patients undergoing sham dialysis (203 μg/ml ± SEM 33) and in patients off dialysis (177 μg/ml ± 42). In vitro aggregometry showed that the uremic milieu does not interfere with the antiaggregating effect of MP. Our results show that MP at the dosage of 30 mg/kg does not affect complement-mediated granulocytopenia in any important way.
A new Low Molecular Weight Heparinoid Org 10172 as Anticoagulant in Hemodialysis
Authors: Von Bonsdorff M. , Stiekema J. , Harjanne A. , Alapiessa U.
Published: April 2018

A low molecular weight heparinoid (Org 10172) was compared with unfractionated heparin in 36 patients on chronic hemodialysis in an open randomized cross-over study with three anti-coagulant treatment regimens for a single hemodialysis session. The anti-coagulant regimens were: a) standard heparin (3250–4750 I.U. heparin at start of hemodialysis followed by continuous infusion of 2000–2700 I.U. per hour); b) Org 10172 administered as a single intravenous bolus of 2400 anti-Xa units at start of dialysis; c) Org 10172 administered as a single bolus of 3200 anti-Xa units at start of dialysis. Plasma anti-Xa activity during hemodialysis was highest in regimen; d) and significantly lower when heparin was used. Mean β-thromboglobulin concentrations changed to the same extent in the three groups. Plasma platelet factor 4 concentrations were higher after the use of heparin. The extracorporeal circuit was maintained patent in all groups; the volume of blood retained in the dialyzers did not differ markedly. Org 10172 proved safe and its anticoagulant effect was sufficient at the dose levels studied.
Iron Metabolism under rEPO Therapy in Patients on Maintenance Hemodialysis
Authors: Bergmann M. , Grützmacher P. , Heuser J. , Kaltwasser J.P.
Published: April 2018

Therapy with recombinant human erythropoietin (rEPO) can correct anemia in RDT patients. However, iron deficiency can develop making treatment unsuccessful. Eighteen non-transfused RDT patients with hematocrit <26% were treated with rEPO to raise the HCT to 30–35%; then the dose was individually adjusted to maintain the HCT. The mean HCT rose from 22.3% to 31.5%. Ten patients received iron substitution before rEPO. During rEPO therapy five further patients had to be supplemented with iron; all patients needed an increase in the oral iron doses and three required i.v. iron. During the correction phase mean serum ferritin dropped from 203 μg/l to a minimum of 71 μg/l and was 102 μg/l after six months. Serum iron and TIBC changed only moderately. It thus appears that iron demand rises markedly during rEPO therapy, requiring iron substitution in most patients. Serum ferritin is the most sensitive parameter for development of iron deficiency.
Treatment of Progressive Systemic Sclerosis by Plasma Exchange: Long-term Results in 40 Patients
Authors: Guillevin L. , Amoura Z. , Merviel Ph. , Pourrat J. , Bussel A. , Sobel A. , Khuy T. , Houssin A. , Alcalay D. , Stroumza P. , Sanderson F. , Levy G. , Frey G. , Ang K.S.
Published: April 2018

The efficacy of plasma exchanges (PE) during the course of scleroderma has only been investigated for short periods. The aim of this study was to follow patients over a long enough period to observe the course of the clinical and paraclinical symptoms in the short, medium, and long term. Forty patients, 24 women and 16 men, were treated by PE and observed for 1–3, 3–12 and over 12 months. Immunological, biological and clinical course and any undesirable side effects were evaluated using a detailed questionnaire. Concomitant therapies were reported and most frequently consisted of corticosteroids, colchicine, factor XIII or vasodilators (nifedipine, captopril). The therapeutic effectiveness of PE was assessed on the basis of improvements in cutaneous, digestive, joint, muscular, lung, cardiovascular and renal lesions. Our findings confirmed the effectiveness of short-term PE on scleroderma (52% of the patients improved during the first 3 months). However, this improvement was transient (5% improvement between 3 and 12 months and only 2.5% over 12 months) and limited to the cutaneous and muscular lesions. Thus, PE cannot be recommended for the treatment of progressive systemic sclerosis.
Newcastle Bone Disease in Hong Kong: A Study of Aluminium Associated Osteomalacia
Authors: Chan M.K. , Varghese Z. , Li M.K. , Wong W.S. , Li C.S.
Published: April 2018

We measured serum aluminium concentrations in 104 haemodialysis patients from 3 centres in Hong Kong. We found that the 52 patients dialyzed in unit A had much higher mean aluminium levels (100 μg/L) than those from the other two units (61 and 39 μg/L respectively). In unit A, where water treatment by reverse osmosis had been introduced only recently, 30.8% of patients had fractures/looser zones, 46.2% had rugger-jersey spine and 28.8% had skeletal erosions. When these patients were divided into two groups according to whether their serum aluminium concentration was below or above 100 μg/l, the latter patients had significantly lower alkaline phosphatase, serum phosphate, and higher total prescribed dose of aluminium hydroxide. It was concluded that both dialysate aluminium and oral aluminium intake seemed to have contributed to the high incidence of osteomalacic fractures among Unit A patients. In eight of these patients serum aluminium increased by more than 150 μg/L after four weeks of receiving 1.5 g desferrioxamine twice weekly. Serial X-rays showed that the mean time after dialysis for the appearance of fractures/Looser zones was 72 months. Three patients developed fractures/Looser zones after successful renal transplantation; and it was postulated that the prompt excretion of aluminium permitted increased osteoclastic activity, resulting in fractures in these patients.
Characterization of L-Histidine Ammonia-lyase Immobilized by Microencapsulation in Artificial Cells: Preparation, Kinetics, Stability, and in Vitro Depletion of Histidine
Authors: Khanna R. , Chang T.M.S.
Published: April 2018

L-histidine ammonia-lyase (histidase) was encapsulated within cellulose nitrate artificial cells, and its kinetic parameters were evaluated. Microencapsulated histidase had an apparent activity of histidase in solution. Encapsulation did not alter the Km of histidase. The Km of histidase solution and the Km apparent of micro-encapsulated histidase were both 20mM. Encapsulation of histidase resulted in increased stability of enzymatic activity at storage temperatures of 4°C and 37°C. At 37°C histidase solution reached 50% of its original activity after 9.5 days of storage, while microencapsulated histidase reached the same level after 15 days. At 4°C histidase solution had 63% of its original activity after 21 days of storage, while encapsulated histidase had 95%. In vitro experiments to evaluate the feasibility of microencapsulated histidase for possible experimental therapy in histidinemia were carried out. These experiments evaluated the effectiveness of encapsulated histidase in depleting histidine. Three different volume ratios of histidase loaded artificial cells to substrate solution were tested. A ratio of 1: 100 allowed 25% histidine depletion after 120 hours. A 1: 50 ratio allowed 35% histidine depletion after 72 hours. A 1: 25 ratio allowed 40% histidine depletion after 24 hours.
Detection of Endotoxin Antibody in Long-Term Dialysis Patients
Authors: Yamagami S. , Adachi T. , Sugimura T. , Wada S. , Kishimoto T. , Maekawa M. , Yoshimura R. , Niwa M. , Terano Y. , Shaldon S.
Published: April 2018

Endotoxins are often seen in dialysate. They are derived from Gram-negative bacteria especially Pseudomonas, E. coli and Serratia. Endotoxins are large-molecular-weight substances with an average molecular weight of 108. These large units can be divided into subunits down to a molecular weight of 10,000 which are thought to pass through dialyzer membranes. To investigate this, endotoxin antibody levels were measured in two groups of patients on chronic regular hemodialysis, a low-flux group using cellulosic membrane dialyzers (cuprophanR and cuproammonium rayon (CAR) and a high-flux group using synthetic polymer membrane dialyzers (PMMA, EVAL). Using an ELISA based on standard endotoxin antibodies the percentages of patients in the low flux group with endotoxin antibodies were 26.9% with Cuprophan and 25% with CAR, not significantly different from a normal control group. In the PMMA and EVAL groups, it was 53.6% and 68.4% respectively. Back filtration of dialysate into blood is understood as the main reason for the entry of endotoxin in patients treated with high-flux dialyzers
Failure of Deferoxamine to Improve Iron Overload in Chronic Hemodialysis Patients
Authors: Roxe D.M. , Krumlovsky F.A. , Del Greco F. , Fitzsimons E.
Published: April 2018

We prospectively studied the in vivo dialytic clearance of iron after deferoxamine (DFO) administration in four stable iron-overloaded chronic hemodialysis patients by quantifying iron concentration in blood entering and leaving the dialyzer and in dialysate after infusions of DFO. No significant arteriovenous iron differences were demonstrated. The mean ratio of venous to arterial iron approached identity at 1.005. All dialysate concentrates used contained large amounts of iron (300–610 μg/dl). No changes in efferent versus afferent dialysate iron concentration could be demonstrated. We conclude (a) iron removal during dialysis with DFO was not demonstrated; (b) the dialysate concentrate tested contained large amounts of iron; (c) in view of potentially significant toxicity, and lack of demonstrable therapeutic benefit, caution in prescribing DFO chelation therapy for iron overload is recommended.
Effect of Erythropoietin Therapy on Diet and Dialysis Clearances in Hemodialysis Patients
Authors: Kaupke C.J. , Vaziri N.D. , Sampson J.R. , Atkins K.
Published: April 2018

Treatment of renal anemia with recombinant human erythropoietin in chronic hemodialysis patients has been reported to lead to increased appetite, and in several studies, to an increase in predialysis serum urea, potassium and creatinine values. We recorded dietary intake, and dialysis clearances for creatinine, urea and uric acid in a group of 12 anemic hemodialysis patients treated with recombinant erythropoietin (epoetin beta). A gradual increase was noted in dietary intake of calories, carbohydrate and sodium during the study period, attaining statistical significance after 10–12 months of therapy. A trend toward increased dietary intake of protein, lipid and potassium was observed, but the differences did not achieve statistical significance. Although a trend toward decreased dialysis clearance at higher hematocrits was found for creatinine clearances did not change significantly for any of the solutes examined, and linear regression analysis did not demonstrate a strong relationship between dialyzer clearance and hematocrit values within the range observed in this study.
A Population Study of Renal Function in Sickle Cell Anemia
Authors: Sklar A.H. , Campbell H. , Caruana R.J. , Lightfoot B.O. , Gaier J.G. , Milner P.
Published: April 2018

To define normal limits for serum creatinine levels, as well as to explore the relationship between age and the prevalence and severity of renal disease in patients with sickle cell anemia (SCA), we retrospectively analyzed renal function parameters in 368 patients followed in our SCA clinic. Dipstick proteinuria was present in 78 patients (20.6%). Chronic renal insufficiency (CRI) was present in 17 patients (4.6%) and showed a high degree of association with proteinuria and increased age. In patients with CRI, the severity of renal dysfunction was also age-related. In the 284 patients without proteinuria or CRI, mean serum creatinine levels were lower than predicted. We conclude that in patients with SCA, serum creatinine levels at the upper limit of normal should be regarded with suspicion, and that the prevalence and severity of proteinuria and CRI in SCA is high and increases with age.
A Simplified Method for Purification, Concentration and Freezing of Bone Marrow Cells for Autologous Transplantation
Authors: Wendel S. , Dayawansa T. , Das P.C. , Smit Sibinga C. Th.
Published: April 2018

Autologous bone marrow (BM) transplantation is being increasingly applied in hematological and oncological patients. However, because of the need to purify and preserve BM requiring high technology, such treatments are virtually concentrated in the “developed” countries. This paper examines methods of BM purification and freezing that could make the technique potentially applicable in developing countries. Hemapheresis is routinely applied for BM purification in our Dutch Centre, where the buffy coats obtained from routine blood donations were utilised in experimental settings. Using DMSO as cryoprotectant, semi-purified white cells were frozen in liquid N2 (LN2), by mechanical freezer or snap-frozen at -55° C. Different types of containers were compared including plastic tubes and ordinary blood bags. After thawing the results show that snap-freezing had a deleterious effect but the cell yields and viability were similar in LN2 or the mechanical freezer where the tubes and the bag were equally effective as containers (86% cell recovery with 90% viability). In the purification/concentration stage, reduction of the volume of the material by extra centrifugation, thus requiring less DMSO, produced better results — 96% cell yield and 90% viability after thawing.

This simplified method was applied in a general hospital in Sao Paulo where four oncology patients underwent BM collection. BM was purified and concentrated within a blood bank facility. Hydroxyethyl starch sedimentation and centrifugation of the material in plastic blood bags gave 80% BM cell harvest. After thawing from the mechanical freezer 1 x 108 BM cells/kg were available for reinfusion to patients. There was no immediate untoward reaction. Three of the patients showed signs of bone marrow regeneration by three weeks, but one patient died 16 days after transplantation, of septicemia. We conclude that certain high-technology procedures for ABMT can be adapted for existing facilities in developing countries.
Comparison of Two Hemodialysis Membranes, Polyacrilonitrile and Cellulose Acetate, on Complement and Coagulation Systems
Authors: Moll S. , De Moerloose P. , Reber G. , Schifferli J. , Leski M.
Published: April 2018

Two hemodialysis membranes, polyacrilonitrile (AN 69) and cellulose acetate (CA), were compared for their effects on complement and hemostasis. Two groups of 5 patients, in dialysis for more than 5 years, were successively dialysed for 4 weeks periods with each type of membrane. We measured C3a (complement activation), platelets and beta-thromboglobulin (platelet activation), thrombin-antithrombin III complexes and fibrinopeptide A (coagulation activation), using C-Reactive Protein as a control for dilution effects. As previously shown, activation of complement was more important with CA than with AN 69 (p < 0.01). In contrast, activation of coagulation (increase in fibrinopeptide A and thrombin-antithrombin III complexes) was more pronounced with AN 69 than with CA.

This study emphasizes the need to consider different biological systems when the bioincompatibility of a hemodialysis membrane is evaluated
Physiopathology and Management of Coagulation during Long-term Extracorporeal Respiratory Assistance
Authors: Uziel L. , Cugno M. , Fabrizi I. , Pesenti A. , Gattinoni L. , Agostoni A.
Published: April 2018

Thrombohemorrhagic risk is one of the main limiting factors in extracorporeal circulation. We describe here our experience in managing some life-threatening hematological complications in 58 patients with acute respiratory failure treated with long-term extracorporeal assistance. These patients were studied by clinical and laboratory means to assess questions related to heparin monitoring, coagulation complications and bleeding incidence. We found that two clotting tests, activated partial thromboplastin time (APTT) and activated clotting time (ACT) can be easily used to assess the safety of anticoagulant treatment (therapeutic ranges: APTT from 55 to 95 sec and ACT from 170 to 220 sec). A certain degree of coagulation activation, despite heparin, was indicated by the constant finding of thrombin-antithrombin complexes, while fibrinolytic activation, measured as plasminogen activator activity, was confined to the time of bypass connection and was of no clinical consequence. Platelet function was always impaired without relation to the platelet loss. Disseminated intravascular coagulation (DIC) (13 episodes) and severe bleeding (11 episodes) were major complications. DIC was corrected with a good outcome for 8 of 13 patients, while severe bleeding was correlated with a poor outcome in 8 of the 11 patients, probably because of the severity of the underlying disease.
Vasoactive Pressure Hormones during and after Cardiopulmonary Bypass
Authors: Kaul T.K. , Swaminathan R. , Chatrath R.R. , Watson D.A.
Published: April 2018

The differences in the pattern of the vasoactive hormone release in response to the stress of surgery and cardiopulmonary bypass (CPB) (pulsatile n = 15 and non pulsatile n = 23) were studied in the adult patients with mitral valve disease (MVD), aortic valve disease (AVD), and the coronary artery disease (CAD). A differential stimulation of the osmoreceptors, baroceptors, renin-angiotensin and the sympathetico-adrenal systems in these patients, resulted in the variations in the pattern of hormone release. Patients with MVD showed a greater stimulation of osmoreceptors, baroceptors and release of Arginine vasopressin (AVP). Renin-angiotensin system was more easily triggered in patients with AVD or CAD; and sympathetico-adrenal system in patients with CAD. The renin-angiotensin-aldosterone axis was better preserved in patients with CAD (r = 0.49, p < 0.001) than in the patients with MVD (r = 0.38, p < 0.02). Plasma renin release showed a significant correlation with noradrenaline release in the patients with MVD (r = 0.47, p < 0.01); but this relationship was lost in the patients with the CAD, due to an excessive noradrenaline release. Pulsatile bypass reduced but did not abolish this response. Under unfavourable conditions, the stress response may persist in the early post-operative period.
Evaluation of Mechanical Loading of a Trileaflet Polyurethane Blood Pump Valve by Finite Element Analysis
Authors: Knierbein B. , Mohr-Matuschek U. , Rechlin M. , Reul H. , Rau G. , Michaeli W.
Published: April 2018

The mechanical loading of the leaflets of a polyurethane blood pump valve at closing pressure (max 300 mmHg) and during the opening phase can be numerically calculated by the finite element method. Geometrical and physical non-linearities, supporting forces by neighbouring leaflets and manufacturing-related thickness distribution are taken into account. The valve housing is assumed to be rigid. Volume forces are neglected. The calculations showed that the critical strain limit of 4.5% (long-term failure limit) was exceeded at closing pressure and during valve opening. During valve operation the connection between leaflet and valve housing and the central leaflet region seem to be the critical areas
The Synthesis of L-tryptophan Degrading Bioreactors
Authors: Schmer G. , Dennis M.B. , Hsueh S. , Hou K.C.
Published: April 2018

To design a bioreactor for removing the potential cancer nutrient L-tryptophan from blood, the L-tryptophan degrading enzyme tryptophan side chain oxydase (TSO) was chemically bound to glutaraldehyde activated gamma amino silane silica and to Zetaffinity microcolumns consisting of a glutaraldehyde activated polyacrylic-cellulose copolymer. Five experiments were carried out in sheep and six experiments in rabbits using a closed circuit plasmapheresis bioreactor system. L-tryptophan in sheep was degraded by the silica bioreactor in a single pass to undetectable levels as measured by high performance liquid chromatography (HPLC). Zetaffinity bioreactors degraded L-tryptophan in rabbits to more than 95% in a single pass. Whole blood L-tryptophan levels changed little throughout the experiment indicating a vast extravascular tryptophan pool. Enzyme leakage from the bioreactor was less than 10−5 IU TSO per ml plasma. The procedures were tolerated well by the animals without any change in vital signs
Computer Aided Time-Lapse Video Analysis of Hepatocyte Morphology during Adhesion to Cellulose Membranes
Authors: Gerlach J. , Vienken J. , Walker P. , Affeld K.
Published: April 2018

An investigation was performed to demonstrate that time-lapse cinematography and computer aided video analysis of cell morphology is suitable to study and compare the characteristics of hepatocytes during the adhesion process to membranes. We chose to compare ordinary cellulose Cuprophan membranes and membranes coated with collagen or fibronectin. Striking differences between uncoated cellulose and fibronectin or collagen coating were seen in the cell count per square millimeter and adhesion behaviour. On the investigated uncoated Cuprophan the hepatocytes were found to attach but not to spread whilst on collagen coated Cuprophan most of the cells spread spherically, and on fibronectin coated membranes most of the cells flattened spherically or polygonally. Time-lapse video microscopy seems to be a valuable technique for assessing the morphologic behaviour of cells in a detailed and quantitative manner in order to improve the hepatocyte culture technique in bioreactors for hybrid systems.
Treatment of Acute Liver Failure with Hemodetoxification Techniques
Authors: Splendiani G. , Tancredi M. , Daniele M. , Giammaria U.
Published: April 2018

The exact pathogenesis of hepatic coma is unknown and this fact has stimulated research in the field of hemodetoxification treatment. We studied 31 patients (19 M and 12 F) with acute hepatic failure and used different detoxification techniques such as hemodialysis, hemoperfusion, hemofiltration and plasmaferesis. We evaluated blood tests, degree of coma and serum levels of middle-molecular weight substances (by gel-chromatography) for each patient.

Our results show that there was an improvement of consciousness and general clinical state in 40% of patients who underwent HD, in 50% of patients treated with HP, in 37.5% of those treated with PF and 78% of patients treated with HF. Unfortunately, the improvement did not last long.

In conclusion we can say that artificial support improves hepatic coma and state of consciousness. This improvement could be due to the better regeneration possibilities of hepatic cells. For this reason hemodetoxification treatment should be started as soon as possible.
Stroma-Free Hemoglobin Solutions Purified by Chloroform and Pasteurization
Authors: Přistoupil T.I. , Mařík T. , Suttnar J. , Štěrbíková J. , Tomsová Z.
Published: April 2018

Several approaches to the processing of native stroma-free hemoglobin solutions (SFH) were reconsidered regarding present requirements for SFH production and quality. Treatment of outdated red blood cells (RBCs) with chloroform and/or by pasteurization were evaluated for technical ease, speed and efficacy in removing stromata, phospholipids and non-heme proteins from RBC hemolysates. The influence of both procedures upon spontaneous hemiglobin formation in stored, preferably freeze-dried SFH was compared. Among other analytical methods, sodium dodecylsulphate Polyacrylamide gel electrophoresis (SDS PAGE) and isoelectrofocusing were used for mutual comparison of the purification procedures. Pasteurized samples were significantly better purified, more homogeneous but also more susceptible to spontaneous oxidation, probably due to heat inactivation of enzymic scavengers of oxygen radicals. On the other hand, the chloroform-treated, unheated SFH samples were less purified from non-heme proteins, but were more stable. Fructose and sucrose were equally active in protecting SFH from oxidation during freeze-drying. At present, the easy chloroform treatment and freeze-drying of thus purified SFH with fructose of sucrose seems to offer a plausible technological compromise which merits further investigation.
Extracorporeal CO2 Removal in a Lung Lavage Induced Respiratory Distress Syndrome
Authors: Zobel G. , Pierer G. , Dacar D. , Berger J. , Novak J.
Published: April 2018

Ten pigs with experimental respiratory distress syndrome were treated by extracorporeal CO2 removal (ECCO2-R) combined with low frequency positive pressure ventilation (LPPV). After lung damage had been induced by repeated lung lavages a PEEP trial was conducted in order to find the appropriate PEEP for the damaged lungs. This PEEP was then applied during the ECCO2-R/LPPV period. Blood gas values improved significantly on extracorporeal bypass within a short time (pre-bypass paO2: 54.2 ± 3.7 vs 168.5 ± 31.6 mmHg after 15 min on bypass, p < 0.001) and were kept constant during the next 4 hours. Minute ventilation (MV) was reduced from 4.01 ± 0.31 to 0.74 ± 0.07 l/min (p < 0.0001), FiO2 of the ventilator from 1.0 to 0.46 ± 0.08 (p < 0.0001) whereas FiO2 of the membrane lung (ML) was not changed significantly (FIO2ML 0.59 ± 0.07 vs 0.53 ± 0.06). During controlled mechanical ventilation (CMV), comparable adequate gas exchange was only achieved at a significantly higher mean airway pressure ([Formula: see text] vs 21.2 ± 0.47 cmH20, p < 0.0001). Hemodynamic variables did not change significantly during bypass time. ECCO2-R/LPPV driven by a simple renal perfusion system allows adequate gas exchange in experimental respiratory failure.
Membranes as Substrates for Hepatocyte Adhesion in Liver Support Bioreactors
Authors: Gerlach J. , Stoll P. , Schnoy N. , Bücherl E.S.
Published: April 2018

Fourteen membranes out of cellulose (CuprophanR), polyamide and polypropylene were compared in a cytocompatibility test using the cytokinetics and cytomorphology of primary hepatatocytes as parameters. Additionally, the impact of coating the membranes with collagen or fibronectin was investigated.

Hepatocytes were not able to attach in acceptable amounts on investigated cellulose membranes. On polyamide and polypropylene membranes a sufficient cell seeding was possible. Coating with collagen or fibronectin improves the attachment and spreading on all membranes. Differences between collagen and fibronectin were detected, observing the morphology of the cells: on collagen, most of the cells spread, whilst on fibronectin, most of the cells spread and flattened polygonally.

If the adhesion of hepatocytes prolongs their metabolic function, a large adhesion surface in bioreactors is necessary. To reach a high surface area for cell adhesion in bioreactors one possibility is the use of polyamide and polypropylene membranes.
On the Need for Erythropoietin Treatment in Dialysis Patients
Authors: Stenver D. , Nielsen B.
Published: April 2018

We evaluated the need for erythropoietin (EPO) treatment in 134 end-stage renal disease patients assuming a level of hemoglobin below 6 mmol/l (9.6 g/dl) as indication for treatment. 91 patients (68%) fulfilled this criterion. Absolute contraindications in 2 patients were previous thrombotic encephalopathy and refusal of treatment. Relative contraindications due to cardiac disease were found in 3 patients. In 15 patients additional treatment was required because of hypertension (5) or deficiency states (10). The implications of elevated serum PTH and aluminum overload are discussed.