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Biomedical subjects

S Stefoni

Publications and source records attributed to S Stefoni.

At least 37 records · Page 2Linked to original sources

Clinical application of sodium profiling in the treatment of intradialytic hypotension.

BACKGROUND: Intradialytic hypotension is mainly induced by the removal of extracellular sodium during dialysis, which impairs intravascular fluid refilling and reduces blood volume. To counter this complication we tested a new kind of profiled hemodialysis (PHD) consisting of the intradialytic modulation of dialysate sodium concentration according to individual profiles set up using a new mathematical model for intradialytic solutes and water kinetics. The clinical aim of this PHD is to stabilize blood pressure maintaining higher blood volume values than standard dialysis treatments. We clinically validated PHD in comparison with constant dialysate sodium dialysis (CHD). METHODS: Twenty hypotensive dialysis patients underwent one PHD and one CHD session maintaining the same dialysis length, sodium mass removal and body weight decrease. A new mathematical model was used to define both the dialysate sodium profiles for PHD and the constant dialysate sodium for CHD. Percent blood volume variation (Crit-line), mean blood pressure, heart rate, cardiac output (Doppler-echocardiography) were monitored intradialitically. RESULTS: Cardiovascular stability improved on PHD as compared with CHD sessions; blood volume and cardiac output during PHD showed a lower decrease than on CHD, the differences statistically significant (from 30' and 60' respectively). Mean blood pressure was, at all time intervals, more stable on PHD than on CHD and was accompanied, on PHD, by a lower heart rate increase (differences statistically significant). CONCLUSIONS: This study shows that PHD performed using dialysate sodium profiles elaborated by our mathematical model obtains, in hypotensive patients, a higher hemodynamic intradialytic stability than CHD, probably due to a higher stabilization of blood volume.

Aged↗

Platelet activation and PDGF-AB release during dialysis.

During hemodialysis the blood-membrane contact causes a release of platelet granule content, which contains Platelet Derived Growth Factor (PDGF-AB). In view of its possible role in accelerated atherosclerotic processes, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during hemodialysis sessions performed with Hemophan and Polysulfone membranes. PDGF-AB, PF4, betaTG and MPV levels were determined in the peripheral blood in 30 patients each of whom underwent 6 dialysis sessions: 3 with Hemophan (HE) membrane and 3 with Polysulfone (PS) membrane, interpolated by a wash out session with PS membrane. Blood samples were taken at times 0', 30', 120', 180', 240' during dialysis sessions and at 1, 4 and 20 hours after the end of the session. Statistical analysis was done using the ANOVA one way test and Student's t test PDGF-AB serum levels initially increased and, except for a sharp fall at 120', remained constantly high during HD with both membranes tested, not returning to basal values until 20 hours after the end of the session. PF4, betaTG and MPV all showed a similar trend to PDGF. No statistically significant difference was found between the two membranes tested. PDGF-AB, a powerful growth factor in cells of mesenchymal origin, is released during dialysis mainly as a result of the blood-membrane contact. This we found regardless of the type of dialyzer we tested, and, above all, proved to return very slowly to basal values. We speculate that the release of PDGF-AB could play a part like other atherosclerosis risk-factors in the appearance and worsening of atherosclerotic lesions in hemodialysis patients.

Aged↗

Reduction of oxaluria after an oral course of lactic acid bacteria at high concentration.

BACKGROUND: Hyperoxaluria is a major risk factor for renal stones, and in most cases, it appears to be sustained by increased dietary load or increased intestinal absorption. Previous studies have shown that components of the endogenous digestive microflora, in particular Oxalobacter formigenes, utilize oxalate in the gut, thus limiting its absorption. We tested the hypothesis of whether oxaluria can be reduced by means of reducing intestinal absorption through feeding a mixture of freeze-dried lactic acid bacteria. METHODS: Six patients with idiopathic calcium-oxalate urolithiasis and mild hyperoxaluria (>40 mg/24 h) received daily a mixture containing 8 x 10(11) freeze-dried lactic acid bacteria (L. acidophilus, L. plantarum, L. brevis, S. thermophilus, B. infantis) for four weeks. The 24-hour urinary excretion of oxalate was determined at the end of the study period and then one month after ending the treatment. The ability of bacteria to degrade oxalate and grow in oxalate-containing media, and the gene expression of Ox1T, an enzyme that catalyzes the transmembrane exchange of oxalate, also were investigated. RESULTS: The treatment resulted in a great reduction of the 24-hour excretion of oxalate in all six patients enrolled. Mean levels +/- SD were 33.5 +/- 15.9 mg/24 h at the end of the study period and 28.3 +/- 14.6 mg/24 h one month after treatment was interrupted compared with baseline values of 55.5 +/- 19.6 mg/24 h (P < 0.05). The treatment was associated with a strong reduction of the fecal excretion of oxalate in the two patients tested. Two bacterial strains among those used for the treatment (L. acidophilus and S. thermophilus) proved in vitro to degrade oxalate effectively, but their growth was somewhat inhibited by oxalate. One strain (B. infantis) showed a quite good degrading activity and grew rapidly in the oxalate-containing medium. L. plantarum and L. brevis showed a modest ability to degrade oxalate even though they grew significantly in oxalate-containing medium. No strain expressed the Ox1T gene. CONCLUSIONS: The urinary excretion of oxalate, a major risk factor for renal stone formation and growth in patients with idiopathic calcium-oxalate urolithiasis, can be greatly reduced with treatment using a high concentration of freeze-dried lactic acid bacteria. We postulate that the biological manipulation of the endogenous digestive microflora can be a novel approach for the prevention of urinary stone formation.

Adolescent↗

Intra- and post-dialytic platelet activation and PDGF-AB release: cellulose diacetate vs polysulfone membranes.

BACKGROUND: During haemodialysis the blood-membrane contact causes a release of platelet granule content, which contains platelet-derived growth factor AB (PDGF-AB). In view of the potential role of this in altering biocompatibility during haemodialysis, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during haemodialysis sessions performed with cellulose diacetate (CDA) and polysulfone (PS) membranes respectively. METHODS: PDGF-AB, platelet factor 4 (PF4), beta thromboglobulin (betaTG), and mean platelet volume (MPV) levels were determined in 30 patients, each of whom underwent six dialysis sessions: three with a CDA and three with a PS membrane. Blood samples were taken at times 0, 15, 30, 120, 180, and 240 min during dialysis and at 1, 4, and 20 h after the end of the session. Statistical analysis was performed using a one-way ANOVA and Student's t test. RESULTS: PDGF-AB at 15 min was increased to +41+/-9% with CDA vs +20+/-5% with PS (P<0.001) from the T0 values, and at 120 min it was +19+/-8% with CDA vs -25+/-9% with PS (P<0.001) from T0 levels. At 240 min it was +95+/-14% with CDA vs +49+/-15% with PS (P<0.001) from the T0 values, returning to basal only 20 h after the end of the session. betaTG at 15 min was +60+/-8% for CDA vs +24+/-7.5% for PS (P<0.001) from the T0 values. PF4 showed a similar trend to betaTG. MPV at 30 min from the start of dialysis was 7.4+/-0.3 fl with CDA and 8+/-0.3 fl with PS (P<0.001), and at 240 min MPV was 7.9+/-0.3 fl with CDA and 8.4+/-0.3 fl with PS (P<0.001). CONCLUSIONS: Platelet activation and platelet release reactions are lower with PS than with CDA membranes. PDGF-AB, released during and after dialysis, represents a clear biocompatibility marker. Its slow return to basal values and its action on vascular cells make it a potential risk factor for atherosclerosis in uraemic patients.

Biocompatible Materials↗

Application of Prastat ELISA in the determination of anti-HLA specificity for immunized patients awaiting kidney transplant: five years' experience.

Three hundred sixty-five patients who underwent cadaver donor kidney transplantation between 1993 and 1998 were divided into four groups: 40 immunized patients with at least one peak panel-reactive antibody (PRA) value more than 50%, 11 hyperimmunized patients with more than three peak PRA values over 50%, 10 retransplanted patients and 304 control patients. Before transplantation, we ascertained the antibody specificities against individual HLA antigens (Prastat Sangstat ELISA method for HLA typing of first donor, husbands of multiparous women and potential donors against whom candidates gave positive cross-matches); thus, patients underwent transplantation excluding the presence of the HLA antigens previously detected and looking for high HLA (class I and II) compatibility. Actuarial graft survival after 12 months was satisfactory in all groups: 87% immunized, 81% hyperimmunized and 80% retransplanted vs 92% controls. Renal function at the end of the first year was similar and the number of rejection episodes in the first 3 months did not significantly differ.

Actuarial Analysis↗

Evaluation of intradialytic solute and fluid kinetics. Setting Up a predictive mathematical model.

A mathematical model of solute kinetics for the improvement of hemodialysis treatment is presented. It includes a two-compartment description of the main solutes and a three-compartment model of body fluids (plasma, interstitial and intracellular). The main model parameters can be individually assigned a priori, on the basis of body weight and plasma concentration values measured before beginning the session. Model predictions are compared with clinical data obtained in vivo during 11 different hemodialysis sessions performed on 6 patients with a profiled sodium concentration in the dialysate and a profiled ultrafiltration rate. In all cases, the agreement between the time pattern of model solute concentrations in plasma and the in vivo data proves fairly good as to urea, sodium, chloride, potassium and bicarbonate kinetics. Only in two sessions was blood volume directly measured in the patient, and in both cases the agreement with model predictions was good. In conclusion, the model allows a priori computation of the amount of sodium removed during hemodialysis, and makes it possible to predict the plasma volume changes and plasma osmolarity changes induced by a given sodium concentration profile in the dialysate and by a given ultrafiltration profile. Hence, it can be used to improve clinical tolerance to the dialysis session taking the characteristics of individual patients into account, in order to minimize intradialytic hypotension.

Bicarbonates↗

Kidney, patient and new millennium nephrology.

The way nephrology develops in the new millennium is bound to be affected by changes in the nephrologist's clinical environment, as well as by the progress made in basic research which will need to find a clinical application. The nephrologist can expect to be more and more involved in renal substitution therapy, not just providing the treatment, but also managing the cost of the service. In the field of nephropathology, the highest expectations surround molecular biology and its application to both acquired and hereditary renal disease; the goal is to find an outlet for gene therapy in clinical practice. Artificial substitution therapy will focus chiefly on the project of 'intelligent dialysis', whereby biological and diagnostic components are combined according the specific needs of the individual patient. The ideal scenario for renal transplantation in the coming millennium would be one where donor supply matches the demand (xenotransplant?), where immunomodulation is perfected, and where diagnoses are based on precise biomolecular events observed in real time.

Humans↗

PDGF-AB release during and after haemodialysis procedure.

BACKGROUND: During haemodialysis blood membrane contact causes the release of the content of platelet alpha-granules, which contain platelet-derived growth factor (PDGF). In view of its possible role in accelerated atherosclerotic processes, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during haemodialysis sessions performed using a cellulosic membrane. METHODS: Using the ELISA method, PDGF-AB, platelet factor-4 (PF4) and beta-thromboglobulin (beta-TG) levels were determined in peripheral blood, as well as in arterial and venous haemodialyser lines, in 10 patients each of whom underwent five consecutive dialysis sessions with a CU membrane. Blood samples were taken at 0, 15, 30, 60, 120, 180 and 240 min during dialysis and at 1, 4 and 20 h after the end of the session. In the same group of patients the levels of the same molecules were also determined after a heparin bolus injection of 4500 IU, blood samples were taken at 0, 15 and 30 min after injection of the bolus. RESULTS: PDGF-AB serum levels increased, remained consistently high during the haemodialysis session (in particular +134+/-20% after 30 min, P<0.001, and +140+/-5% after 240 min, P<0.001) and returned to basal values only after 20 h following the end of the session. PF4 and beta-TG showed a similar trend to PDGF. The heparin bolus injection caused only a small increase (+15+/-5% at 30 min) in PDGF-AB serum levels. CONCLUSIONS: PDGF-AB is released during dialysis mainly as consequence of the blood-membrane contact and it returns only slowly to basal values.

Adult↗

Effects of dialysis membrane nature on intradialytic phagocytizing activity.

Blood-membrane contact in the extracorporeal circuit affects the activation of many biological systems. Among these, phagocytizing activity has been reported to be influenced by the nature of the hemodialysis membrane used, whether cellulosic or synthetic. This work reports on an ex-vivo, comparative test between cellulosics and synthetics concerning the effects of blood-membrane contact on the polymorphonucleate and monocyte phagocytizing function, both during and after the hemodialysis session. By means of flow cytometry, we evaluated the capacity for phagosoma formation and oxidative burst both in polymorphonucleates and monocytes. Ten hemodialysis patients were included in the study. Six separate dialysis procedures for each patient were considered, one per dialyzer (3 cellulosic and 3 synthetic membranes). Tests were performed at 15', 60', 210' and 4 hours after the session end. Comparative evaluation was made according to Student's t test. Polymorphonucleate phagocytosis and oxidative burst activation were globally more marked for synthetic than cellulosic membranes, tending to level out in the post-dialysis. This result could be affected by their functional exhaustion following pulmonary sequestration. Monocyte intradialytic phagocytosis and oxidative burst proved more activated by cellulosic membrane. All differences tended to vanish in the post-dialysis.

Flow Cytometry↗

Mathematical modeling of solute kinetics and body fluid changes during profiled hemodialysis.

A mathematical model of solute kinetics oriented to improve hemodialysis treatment is presented. It includes a two-compartment description of the main solutes (K+, Na+, Cl-, urea, HCO3-, H+, CO2), acid-base equilibrium through two buffer systems (bicarbonate and non-carbonic buffers) and a three-compartment model of body fluids (plasma, interstitial and intracellular). The main model parameters can be individually assigned a priori, on the basis of body weight and plasma concentration values measured before beginning the session. Model predictions are compared with clinical data obtained during 11 different hemodialysis sessions performed on six patients with profiled sodium concentration in the dialysate and profiled ultrafiltration rate. In all cases, the agreement between the time pattern of model solute concentrations in plasma and clinical data turns out fairly good as to urea, sodium, chloride and potassium kinetics. Finally, the time patterns of plasma bicarbonate concentration and pH can be reproduced fairly well with the model, provided CO2 concentration remains constant. Only in two sessions, blood volume was directly measured in the patient, and in both cases the agreement with model predictions was good. In conclusion, the model allows a priori computation of the amount of sodium removed during hemodialysis, and may enable the prediction of plasma volume changes and plasma osmolarity changes induced by a given sodium concentration profile in the dialysate and by a given ultrafiltration profile. Hence, it can be used to improve the dialysis session taking the characteristics of individual patients into account, in order to minimize intradialytic imbalances (such as hypotension or disequilibrium syndrome).

Acid-Base Equilibrium↗

Severe gastrointestinal bleeding in a uremic patient treated with estrogen-progesterone therapy.

Gastrointestinal bleeding is a frequent complication in hemodialysis patients; angiodysplasia is a potential cause, with a higher incidence in uremic patients. We describe a case of severe anemia (Hemoglobin up to 3.5 g/dl) secondary to diffuse angiodysplastic lesions in a hemodialysis patient with mixed connective tissue disease. The case is characterised both by the severity of the clinical picture (extension and entity of angiodysplastic lesions, frequency of bleeding episodes) and by the patient's religious faith which made her reject blood transfusions. We underline the efficacy of estrogen-progesterone therapy in view of the modest results obtained with other therapeutic strategies on bleeding.

Adult↗

Mismatch-specific anti-HLA antibody production following aorta transplants.

In this study, we have investigated the nature and magnitude of the immunological response after implantation of human aortic segments. Five recipients of aortic segment replacement were studied for anti-HLA antibody production (specificity and Ig class), CD3, CD4, and CD8 T cell subpopulation dynamics, and aortic wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were first detected 1-3 months after implantation and persisted in high concentrations for at least 1 year. Computer tomography scanning showed a progressive thickness of the aortic wall. Also the absolute number of CD3, CD4, and CD8 positive lymphocytes increased progressively after implantation. In conclusion, as was observed earlier for heart valve allografts, human implanted aortic segments induce a strong anti-HLA antibody response in recipients. We speculate that these antibodies have the potential to harm the implant, for example, by having an impact on luminal narrowing.

Antibodies↗

Beta2-microglobulin and low-flux synthetic dialyzers.

The aim of this study was to compare the effect on beta2-microglobulin (beta2-M) plasma levels of dialyzers with 3 low-flux synthetic membranes and regenerated cellulose (Cuprophan) in 12 chronic dialysis patients. The synthetic membrane materials chosen were low-flux polymethylmethacrylate (PMMA), low-flux polysulfone (PS 400), and polycarbonate-polyether (Gambrane). Adequate and comparable removal of small solutes was provided by dialyzers with all 4 membrane materials used under similar conditions. A significant reduction of beta2-M plasma levels was seen only with Gambrane while the other 2 synthetic membrane materials gave rise to increases similar to those known to occur with Cuprophan. After correction for the hemoconcentration caused by ultrafiltration, dialysis with Gambrane showed a 24% lower plasma beta2-M level while the beta2-M concentrations with the other 3 membrane materials were practically unchanged. In addition, the efficiency of Gambrane dialyzers in beta2-M removal was able to significantly lower the predialysis plasma beta2-M levels after only 5 dialysis sessions. The hemocompatibility of the 3 synthetic low-flux membranes as judged by the white blood cell (WBC) count and complement activation was similar and therefore cannot be used to explain the different beta2-M plasma levels. In anticipation of gaining further insight into the mechanisms of accumulation and deposition of beta2-M in dialysis patients, a worthwhile approach may be to use a low-flux membrane such as Gambrane which combines removal with protection against potential activating factors in the dialysis fluid.

Aged↗