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Biomedical subjects

S Sforzini

Publications and source records attributed to S Sforzini.

At least 37 records · Page 2Linked to original sources

Use of anti-CD3 and anti-CD16 bispecific monoclonal antibodies for the targeting of T and NK cells against tumor cells.

To target T lymphocytes against EGF-R+ tumors, we constructed anti-CD3/anti-EGF-R bimAbs either by the generation of a hybrid hybridoma (quadroma) or by a chemical cross-linking method. Analysis of the in vitro functional activity of these two different constructs indicated that the quadroma-secreted bimAb was more efficient in targeting the CD3+8+ clones against EGF-R+ target cells with respect to the bimAb produced by chemical method. In addition, the quadroma-produced bimAb is able to induce cytolysis of EGF-R+ tumor cell lines of PHA-induced lymphoblasts that had been expanded in IL-2-containing medium, whereas tumor cells lacking expression of EGF-R were not lysed. Resting PBL targeted by the bimAb did not display significant cytotoxicity against the relevant tumor. An anti-CD16 hybridoma (IgG1) was fused with an anti-folate-binding protein hybrid (IgG2a) to construct bimAbs to target NK cells against NK-resistant ovarian carcinomas. The hybrid IgG1/IgG2a bimAb triggered the specific lysis of relevant target cells by resting NK cells, but it was ineffective when CD8+TCR alpha/beta+ cultured cell populations were used as effectors. Only marginal increases of cytolytic activity could be induced by the bimAb when IL-2-activated PBL (i.e., LAK cells) were used as effectors due to the high cytolytic activity of these cells against the relevant tumors in the absence of bimAb. The possible use of anti-CD16 or anti-CD3 bimAbs for the development of different cellular immunotherapy strategies against cancer is discussed.

Antibodies, Bispecific↗

Ventricular arrhythmias and four-year mortality in haemodialysis patients. Gruppo Emodialisi e Patologie Cardiovascolari.

127 randomly selected patients on haemodialysis showed a high prevalence of ventricular arrhythmias, the frequency of which rose significantly during and after dialysis. These patients have now been followed up for 4 years. Only age and ischaemic heart disease correlated independently with mortality. Although ventricular arrhythmias are often associated with cardiac disease in patients on chronic haemodialysis, they do not seem to predict overall mortality.

Arrhythmias, Cardiac↗

Forecasting correct sodium balance in hemodiafiltration procedures involving infusions.

Four patients, stable on acetate hemodialysis (AHD), were switched to acetate-free biofiltration (AFB) which differs from AHD and bicarbonate hemodialysis (BHD) in that the dialysate contains no buffer, which is given intravenously as a hypertonic (1/6 M) Na bicarbonate solution. Within the 1st month the patients developed thirst and hypertension attributed to a positive Na balance. The aim of this investigation was to check this (1) by a study based on the predictable changes induced in the body compartments of 13 patients by the infusion and ultrafiltration (UF) of a hypertonic solution and (2) by direct determination and calculation of 28 Na mass balances in BHD and AFB. The theoretical model indicated that infusion of 4.87 liters of a 166.7 mEq/l Na bicarbonate solution and UF of the same amount caused a positive balance of 233 mosm of Na. The Na mass balances showed a relationship between Na transmembrane gradient and loss or gain of Na in both methods (p less than 0.0001). The slopes of the regression lines were not significantly different but there was a highly significant difference between the y axis intercepts (p less than 0.0001), which indicates that the same Na transmembrane gradient that gives no net change of Na in BHD, induces a net gain of 240 mosm (120 mEq of Na) in AFB and that to obtain the same Na balance dialysate Na should be reduced by about 8 mEq/l in AFB. These data are the same as the theoretical forecast which could be extended to all hemodiafiltration methods in which solutions of any tonicity have to be infused, in order to correctly predict the Na balance.

Body Fluid Compartments↗

Transport of water and solutes in uremic patients with chronic hepatic disease in CAPD.

Ten patients with chronic hepatic disease (CHD) were compared with 34 non-CHD (N) pts. All patients underwent a peritoneal equilibration test; the asymptotic curves for small solutes transport were transformed into straight lines; protein transport was also expressed as a straight line; the slopes of these linear functions were used as index of solute transfer. CHD patients showed increased UF and transport of all solutes. The well-known relationships between UF and glucose absorption and between UF and dialysate sodium concentration were observed in N, but not in CHD patients. In patients without hepatic disease there was also a relationship between UF and the glucose transport slope, which was not observed in CHD pts. These results are probably due to the influence of hepatic lymph production plus increased lymphatic removal, observed in non uremic patients affected by cirrhosis, on the mechanisms of water and solute transport in CAPD. CHD patients can be managed either with CAPD or with short frequent exchanges. Ascites production can be evaluated by the difference between the observed UF in a patient with CHD and the expected UF in N patients.

Biological Transport↗

Potassium removal as a factor limiting the correction of acidosis during dialysis.

The diffusional fluxes of urea, potassium and bicarbonate across the dialysis membrane (external balance) were determined in seven patients during haemodialysis using potassium free dialysate and dialysate containing 2.0mEq/L of potassium. The results show an inverse correlation between extraction of potassium and intake of bicarbonate in both external and internal balances. This is probably due to the increase in cell membrane electrical potential resulting from a fall in blood potassium and emphasises the importance of electrical driving forces in diffusional fluxes across cellular membranes.

Bicarbonates↗

[Potassium removal: a factor limiting the correction of acidosis during dialysis].

The diffusional fluxes of urea, potassium and bicarbonate across the dialytic membrane (external balance), and across the cellular membrane (internal balance), were determined in 7 patients in haemodialysis using potassium free dialysate and dialysate containing 2.0 mEq/1 of potassium. The results obtained show an inverse correlation between extraction of potassium and intake of bicarbonate in both external and internal balance. This is probably due to the increase in membrane electrical potential resulting from a fall in blood potassium and emphasizes the importance of electrical driving forces in diffusional fluxes across cellular membranes.

Acidosis↗

Hemodialysis with "adequate" sodium concentration in dialysate.

This investigation was undertaken to define the "adequate" sodium concentration in the dialytic fluid allowing to maintain a stable plasma effective osmolality during dialysis. Isonatric dialysate is shown to miss this aim by inducing a predictable postdialytic hypernatremia. To avoid this effect a new approach was made. 17 clinically stabilized patients, previously dialyzed over a period of at least 2 years with a dialysate sodium concentration of 133 mEq/l, underwent dialysis with the "adequate" sodium concentration in the dialysate for over 3 years. During dialysis cramps, headache, hypotension, hypertensive crises and postdialytic weakness were reduced in frequency and nearly disappeared. No deterioration in blood pressure control occurred and improvement in some general parameters (hematocrit, glucose and insulin metabolism, well-being) was reported after prolonged treatment.

Adult↗

Ultrafiltration and high sodium concentration dialysis: pathophysiological correlation.

Five stabilised uraemic patients underwent two different procedures using the Gambro Ultradiffuser: ultrafiltration alone for one hour (mean body weight loss 2.97 +/- 0.24 kg) and ultrafiltration with simultaneous dialysis for one hour (mean body weight loss 2.92 +/- 0.22 kg) using a given dialysate sodium concentration which reproduced the changes in osmolality which occur during ultrafiltration alone. This mean sodium concentration was 154.75 +/- 2.02 mEq/L. The results did not show significant differences for the two procedures as regards tolerance to dehydration. These results underline the key role of osmolar stability in making dehydration tolerable.

Blood Pressure↗