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Biomedical subjects

A Brendolan

Publications and source records attributed to A Brendolan.

At least 19 recordsLinked to original sources

A new scintigraphic method to characterize ultrafiltration in hollow fiber dialyzers.

Ultrafiltration and pressure profiles in hollow fiber dialyzers with different hydraulic permeabilities have been investigated with a new scintigraphic method. Radiolabelled albumin macroaggregates, used as a nondiffusible marker molecule, were added to the blood in an in vitro circuit and circulated through cuprophan and polysulphon dialyzers. Since the marker molecule was too big to cross the dialysis membrane, its changes in concentration were assumed to occur in response to the variation of the blood water content (filtration or back-filtration). These changes in concentration, recorded by a gamma camera, were evaluated to establish the cumulative values of filtration and back-filtration and their relevant profiles along the length of the dialyzer. The achieved data were compared with the experimental values of ultrafiltration empirically measured and with the theoretical values predicted by a classic linear method. Two conditions were analyzed: A) the minimal filtration rate necessary to avoid back-filtration (critical filtration); and B) the condition of zero net filtration in which filtration equals back-filtration. The nuclear method proved to be extremely precise in predicting the ultrafiltration values and significantly more precise than the linear method, especially for the highly permeable dialyzer. The reason for that probably depends on the non-linear pressure and ultrafiltration profile observed with the scintigraphic pattern of the dialyzer. Viscosity changes and local variations in blood flow may in fact interfere with the pressure drop inside the hollow fibers and result in such a complex behavior. The other interesting aspect of this method is the possibility of accurate measurement of the amount of back-filtration that wouldn't be possible with simple calculations. In conclusion, the complex nature of the phenomena regulating the water fluxes in hollow fiber dialyzers requires more complex calculation than a simple linear model to achieve an accurate range of predictability.

Biophysical Phenomena

Ultrafiltration and pressure profiles in continuous arterio-venous hemofiltration studied by computerized scintigraphic imaging.

Clotting of the filters in continuous arterio-venous hemofiltration (CAVH) has been frequently related to filtration pressure equilibrium (FPE). The geometry of the filter and the blood flow, together with filtration fraction, are the factors affecting FPE. A new method based on scintigraphic imaging of the filter is described to demonstrate FPE and identify the operational conditions influencing it. A radiolabelled marker molecule (albumin macroaggregates + Tc99) is added to the blood circulating at various flows through the filter. Changes in the concentration of this molecule detected by a gamma camera are used to calculate the water fluxes in different sections of the filter. When the curve reaches a plateau, no further changes occur and FPE is achieved. The study used Amicon D-30 hemofilters and FPE points were achieved for blood flows of 75, 110 and 150 ml/min respectively 8 cm, 12 cm and 18 cm from the inlet. The study not only demonstrates the occurrence of FPE, but also identifies the length of the filter required at a given blood flow to avoid FPE (achieving less clotting and lower heparin requirement). The Amicon diafilter family, having filters of different length, is useful for "personalizing" the filter in CAVH.

Blood Coagulation

Paired filtration dialysis: studies on efficiency, flow dynamics and hydraulic properties of the system.

Several strategies have been proposed to increase dialysis efficiency in order to reduce dialysis treatment time. Paired filtration dialysis (two-chamber technique) is a new technique combining the advantages of highly permeable membranes and convective transport with the high depurative efficacy of diffusion. The system operates with two units in series (hemofilter + dialyzer) with membranes of polysulfone and hemophan, respectively. A detailed analysis of the hydraulic properties of the system and its possible optimization in terms of depurative efficiency is reported in this paper. In vitro and in vivo tests provided data sufficient to draw some hypotheses on a new utilization of the system. The system appears to be adequate for operating under conditions of high blood flows, however, some limitations were evidenced during our evaluation: the convective component may be insufficient and further increases are impossible because of the limiting effect of the low surface area of the hemofilter; the configuration in which the weight loss is achieved in the hemofilter exposes to the risk of backfiltration in the dialyzer, reducing the benefits of a highly biocompatible system, and the use of acetate in the dialysate and/or lactate in the substitution fluid may interfere with a satisfactory correction of metabolic acidosis. On the basis of our evaluations, some changes can be proposed such as: (1) increased surface area of the hemofilter; (2) use of blood flows higher than 300 ml/min; (3) use of bicarbonate in the dialysate and in the replacement solution; (4) increased convective component with ultrafiltration rates of 50-60 ml/min and full replacement with substitution fluid in between the two filters, and (5) weight loss achieved in the dialyzer with a constantly positive transmembrane pressure. With such a modification of the operative conditions, paired filtration dialysis can be probably applied as a highly efficient dialysis technique in a large number of patients with a significant reduction of dialysis treatment time.

Blood Flow Velocity

Alpha-1-antichymotrypsin in renal biopsies.

Alpha 1-Antichymotrypsin (alpha 1-AK) and alpha-1-antitrypsin (alpha 1-AT) represent a defense mechanism to protect the tissues from proteolytic enzyme activity. We studied the implication of alpha 1-AK and alpha 1-AT in glomeruli of patients with different nephropathies based on the analysis of 52 paraffin-embedded renal biopsies with alpha 1-AK and alpha 1-AT antisera. The results demonstrate an intense alpha 1-AK glomerular staining in renal biopsies from patients with minimal-change disease, while a minor staining of this protein was found in the other nephropathies. No significant evidence of alpha 1-AT deposits was observed in our cases. Our findings suggest that when alpha 1-AK is lacking in glomeruli the defense mechanisms against proteolytic enzymes may not be efficient enough to protect the glomerular structures and limit the damage. Since alpha 1-AK is a reactant of the acute phase of inflammation, it may be considered as a marker of activity for monocyte-macrophages in glomerular damage.

Biomarkers

Pathophysiology of ultrafiltration in peritoneal dialysis.

Pathophysiology of peritoneal ultrafiltration is analyzed in the present study. Peritoneal equilibration test is the easiest procedure to study in detail the possible causes of failure to control the ultrafiltration rate in patients undergoing peritoneal dialysis. Membrane failure, reduction in peritoneal blood flow, excessive lymphatic reabsorption catheter malposition, and fluid sequestration are the most common causes of ultrafiltration loss. Pharmacologic manipulation of peritoneal membrane, correction of mechanical inconvenients, reduction in peritonitis rate and in the level of immunostimulation of the mesothelial macrophages, together with a careful policy in terms of glucose concentration in the dialysate and dwell times may contribute not only to treat different forms of ultrafiltration loss but also to prevent their incidence.

Algorithms

Acid base correction in bicarbonate CAPD patients.

Bicarbonate has been proposed as buffer in CAPD solutions in recent years instead of lactate and acetate. The present study is designed to evaluate peritoneal bicarbonate kinetics using bicarbonate solutions. Seventy kinetic studies have been performed in 7 patients treated with 2 CAPD solutions containing 35 mmol/l (A) and 27 mmol/l (B) of bicarbonate. The changes in dialysate bicarbonate concentration at different dwell times were correlated with bicarbonate blood levels. Furthermore after 2 hours of dwell time and at subsequent observations, no differences in dialysate bicarbonate concentration were found between A and B solutions at the same bicarbonatemia. Thus a feedback between bicarbonate absorption and bicarbonate blood concentration was observed. If the amount of bicarbonate transferred to the patient is over the metabolic acid production, bicarbonatemia will rise: consequently bicarbonate dialysate absorption will decrease. After a few days, an equilibrium point will be reached. In this condition the bicarbonate absorption is equal to metabolic acid production and, in stable clinical conditions, a stable acid base status will be maintained by the patient. Our studies empirically demonstrated that the equilibrium is reached when a difference of 5 mmols between blood and inlet dialysate bicarbonate concentration is observed. Consequently to achieve 25 mmol/l of bicarbonatemia, the bicarbonate concentration of CAPD solution should be about 30 mmol/l.

Acetates

Technical and clinical evaluation of a new synthetic low flux polysulphon membrane for hemodialysis.

New synthetic membranes have been developed to reduce the ultrafiltration coefficient (Kf) maintaining an adequate permeability to medium-large solutes and a good biocompatibility. The new Fresenius F6 Low Flux Polysulphon Membrane is studied in this paper as far as hydraulic and permeability properties are concerned. For this purpose in vitro and in vivo tests have been carried out in a series of different conditions. In vitro sieving coefficients were near 1 for solutes with molecular weight up to 5000 Daltons. The ultrafiltration coefficient of the device was 5.4 ml/h/mmHg while the value of Kf normalized per square meter was lower than 5 ml/h/mmHg. The geometry of the blood path was adequate even operating at high blood flows without excessive resistance and obligate filtration. This resulted in vivo in a good performance during short dialysis schedules with good clearances of small and large molecules and with no risks of backfiltration. In fact, the low permeability to water permits constant operation with positive transmembrane pressures without excessive ultrafiltration rates. The biocompatibility of the membrane was excellent and high capacity of adsorption for beta-2 microglobulin was demonstrated. These results suggest that these membranes seem to be able to join the advantages of the traditional cellulosic membranes and of the newer synthetic membranes reducing their relative disadvantages.

Biocompatible Materials

New method of extracorporeal concentration of ascitic fluid as a treatment of refractory ascites.

A new piece of equipment for the treatment of ascites is described. Ascitic fluid is drained by gravity in a unit consisting of an Amicon D-30 ultrafilter and a bag used as transit reservoir placed below the patient. When the bag is full, it is raised to a height sufficient to let the fluid flow back through the filter to the peritoneal cavity. Mainly during this step ultrafiltration of ascitic fluid occurs through the membrane of the filter. Ultrafiltration is enhanced by the negative pressure created in the filtrate compartment due to the height difference between filter unit and filtrate drainage bag placed at the bottom of the machine. Proteins in the ascitic fluid are retained and returned to the abdominal cavity. The machine cycle is automatically repeated as many times as necessary to achieve the scheduled patient weight loss. 17 patients have been treated for a total of 1.94 sessions/patient with reinfusion of the fluid in the abdominal cavity. In all patients a significant reduction of the amount of ascitic fluid and of its rate of formation have been achieved. The treatment was well tolerated and no side effects were observed. After treatment the diuresis and the sodium excretion increased significantly in all patients. The system is safe and reliable for the treatment of refractory ascites without major complications.

Adult

High-flux haemodialysis with 1.5 m2 modified cuprammonium rayon membrane: technical and clinical evaluation.

The feasibility and reliability of a short dialysis technique performed with standard dialysis equipment and a modified cuprammonium rayon hollow-fibre filter has been studied. The hydraulic response of the filter and membrane to high blood flows and transmembrane pressures were tested in vitro and the maximal clearances of different solutes achievable during high-flux bicarbonate dialysis were studied in vivo. Clinical studies were undertaken to evaluate the long-term effects of the short, highly efficient dialysis therapy. Six patients were treated for more than a year with single-pass bicarbonate dialysis with a blood flow of 500 ml/min, dialysate flow of 700 ml/min, and average duration of 150 min/session three times weekly. The treatment showed an adequate efficiency with an average KT/V greater than 1. All patients obtained an average blood urea nitrogen during the study of less than 80 mg/dl and an average protein catabolic rate of 0.9 g/kg per 24 h. The treatment was well tolerated by all patients and, on echocardiography, no significant changes in myocardial function were detected after one year of therapy. The treatment is efficient, well tolerated, simple to monitor and does not require the use of synthetic membranes or machines with advanced technology. Thus the reduction of dialysis treatment time is feasible in all centres at a relatively low cost.

Adult