[Effects of different dialysis membranes and techniques on the nutritional status, morbidity and mortality of hemodialysis patients]. / Effetti di diverse membrane e metodiche dialitiche sullo stato nutrizionale, morbilità e mortalità di pazienti emodializzati.

To evaluate long-term effects of different hemodialysis (HD) membranes and techniques on nutritional status, morbidity, and mortality in HD patients, we prospectively studied 138 stable HD patients (59 females, 79 males, mean age 53 +/- 13 yrs) on maintenance HD from at least 1 yr with bicarbonate (BD) and cellulose acetate (AC). Patients were randomly assigned to one of four groups: comparable for age, sex, underlying nephropathy, time on dialysis, comorbidity, and followed-up for 5 yrs. Group A (n=38) BD/AC; group B (n=30) BD/low-flux polysulfone (PS); group C (n=30) BD/middle-flux PS or PA; group D (n=20) hemodiafiltration (HDF)/high-flux polysulfone (PS-HDF); group E (n=20) acetate free biofiltration (AFB) with PAN. Nutritional status was evaluated by anthropometric index, visceral protein compartment index, immunological index and bioelectrical impedance analysis. In all patients, we evaluated yearly plasma values of Beta2-microglobulin and of C-reactive protein (CRP) before and after dialysis. A significant and sustained improvement in nutritional status and a striking reduction in CRP and in pre- and post-dialysis beta2-microglobulin levels was observed in groups C, D and E. Morbidity (calculated from the number of clinical complications/patient/yr and from the number of hospital admissions/patient/yr) and mortality were significantly higher in groups A and B (mortality: group A=24%, group B=23%, group C=10%, group D=5%, and group E=5%; p<0.001). The results of our study indicate that the use of middle and high-flux biocompatible membranes is associated with a remarkable and sustained amelioration in nutritional status and with a significant improvement in the prognosis of HD patients, explained by the notable reduction in beta2-microglobulin and in the systemic inflammatory response.

Immunoresponsiveness of cancer patients: effect of blood transfusion and immune reactivity of tumor infiltrating lymphocytes.

The immunoreactivity of cancer patients submitted to surgery and perioperatively transfused was investigated. Peripheral blood mononuclear cells (PBMC) and tumor infiltrating lymphocytes (TIL) were tested for the natural killer (NK) cytotoxic activity, for the in vitro synthesis of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2). The serum levels and the production of PGE2 by PBMC were significantly higher in patients than in controls, whereas no significant differences in the tested immunological variables emerged between the two groups of subjects. Instead, TIL produced significant larger amounts of spontaneous PGE2 (p < 0.001) and significant lower amounts of IFN-gamma (p < 0.001) and TNF-alpha (p < 0.001) than autologous PBMC, suggesting an involvement of PGE2 in the impairment of the host immunoreactivity at the tumor site. To evaluate the immunomodulating effect of blood transfusion, the patients were reexamined 8 to 20 days after surgery. No differences were found in the NK cytotoxic activity, lymphokine synthesis, serum levels, and production of PGE2 between transfused and untransfused patients. These results do not support the hypothesis that blood transfusions negatively affect the immune response of neoplastic patients.

Circulating platelet activation in healthy subjects and in some pathological conditions. Method of study and results.

Current clinical methods for evaluating platelet function are artful tests which study the effects of various stimuli on platelets, whereas the clinician is much more interested in methods evaluating the activation of circulating platelets. The hallmark of activation of platelets is their shape change, i.e. the transformation of the platelets from smooth disks into spiny spheres; the aggregation begins when 30% of platelets are activated. In 1138 subjects (384 healthy individuals and 854 patients with various pathological conditions with high thrombotic risk) we have investigated circulating platelet activation and circulating platelet aggregates by fixation of blood cells in a glutaraldehyde mixture and by evaluation of platelet shape change and aggregates on a phase-contrast microscope. The method is precise, accurate and suitable for clinical purposes.

Effects of oral and intravenous defibrotide on blood viscosity in patients with peripheral obliterative arterial disease.

Patients with peripheral obliterative arterial disease received 400 mg of defibrotide intravenously (seven patients) or orally (nine patients). Blood and plasma viscosity were measured before therapy, at 30 minutes after and one hour after intravenous administration, and at 1, 2, 3, and 8 hours after oral administration. Thirty minutes after intravenous administration, blood viscosity at a shear rate of 30 sec-1 was reduced from 9.99 to 9.00 and at a shear rate of 180 sec-1 from 6.61 to 6.33 (P less than 0.05). Viscosity returned to baseline after 60 minutes. At 1, 2, and 3 hours after oral administration, blood viscosity at a shear rate of 30 sec-1 was reduced from 8.53 to 7.44, 6.88, and 7.19 (each P less than 0.01) and at a shear rate of 180 sec-1 from 5.88 to 5.51 (P less than 0.05), 5.14 (P less than 0.05), and 5.38 (P less than 0.01); the levels at eight hours were not significantly different from baseline values. Plasma viscosity was not affected by defibrotide. These data confirm previous evidence of a rheologic effect of defibrotide in patients with peripheral obliterative arterial disease and indicate that such an effect can be achieved with oral administration.