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Biomedical subjects

G Segoloni

Publications and source records attributed to G Segoloni.

At least 37 records · Page 2Linked to original sources

Production of cytokines in hemodialysis.

Tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1 beta) are cytokines primarily produced by monocytes/macrophages when stimulated by endotoxin, complement-derived anaphylatoxins and the specific antigen. In the present study, the plasma levels of TNF-alpha and IL-1 beta were evaluated before and after hemodialysis with cuprophane membrane (in 9 patients) and hemodiafiltration (in 9 patients) using three high-permeability membranes such as polymethylmethacrylate, polyacrylonitrile (AN-69) and polysulfone. In vitro spontaneous production of TNF-alpha and IL-1 beta was evaluated in the supernatants from short-term cultured monocytes obtained before and after treatment. The predialytic levels of TNF-alpha and IL-1 beta were significantly higher (p less than 0.05) in the uremic population than in 21 healthy subjects taken as controls. The analysis of the uremic population regarding the mode of therapy indicated that in hemodialysis the predialytic plasma levels of TNF-alpha and IL-1 beta did not significantly differ from those of healthy subjects. In contrast, in hemodiafiltration with polymethylmethacrylate and AN-69, but not with polysulfone, the predialytic plasma levels of both cytokines were significantly (p less than 0.05) increased. No significant variation in plasma levels of both cytokines was observed after hemodialysis with cuprophane membranes. Hemodiafiltration with polymethylmethacrylate and AN-69, but not with polysulfone, brought about a consistent reduction in plasma levels of both cytokines. Detectable amounts of TNF-alpha and IL-1 beta were spontaneously produced by peripheral-blood monocytes 6 h after the end of hemodialysis but not of hemodiafiltration. These studies suggest a possible role of TNF-alpha and IL-1 beta in the biocompatibility of different extracorporeal treatments.

Acrylic Resins↗

Release of platelet-activating factor in systemic lupus erythematosus.

The biologically active 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet-activating factor; PAF) is inactivated in plasma mainly by a specific PAF acetylhydrolase (1-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine acetylhydrolase; EC 3.1.1.48). In the present study, PAF was released in detectable amounts (5.4 +/- 2.9 ng/ml; mean +/- 1 SD) in the plasma of 8 out of 10 patients with systemic lupus erythematosus (SLE) during the most active phases of the disease. PAF was never detectable in the plasma of patients with inactive SLE or of healthy subjects. PAF acetylhydrolase activity was markedly reduced in sera of 10 patients with active SLE as compared to 7 patients with inactive SLE, 16 patients with rheumatoid arthritis (RA), 5 patients with nephrotic syndrome (NS) and 15 healthy subjects. A kinetic study of the enzyme in patients with active SLE suggested an overall reduced activity rather than an intrinsic defect of the enzyme. PAF acetylhydrolase in sera of patients with active SLE shared with that of healthy subjects the same substrate specificity, sensitivity to enzymatic and chemicophysical treatments and association to low-density lipoprotein (LDL), acting as carrier of PAF acetylhydrolase in plasma. However, the protein concentration of LDL was significantly reduced in patients with active SLE as compared to patients with inactive SLE, RA and NS and to healthy subjects, thereby suggesting that the reduction of PAF acetylhydrolase activity in active SLE might be due at least in part to a carrier defect related to the activity of the disease. In addition, experiments in which serum of patients with active SLE and serum of healthy subjects were mixed in different combinations indicated the absence of factors inhibiting PAF acetylhydrolase activity in SLE patients.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Clinical and histological results of long-term management of aluminium overloading in uraemic patients with desferrioxamine.

Aluminium introxication in uraemic patients has been reported both in epidemic and sporadic forms. Desferrioxamine (DFO) results in strong Al mobilisation, but definitive treatment schedules, times of stop, and actual long-term Al removal her not been established. This study was carried out on three sporadic cases of Al intoxication treated with DFO for 3 1/2, 4 1/2 and 1 years. Clinical and laboratory parameters were employed to check the brain, bone and red cell status. Direct evaluation of Al kinetics showed that actual Al removal may be overestimated. In our experience it did not exceed 100 mg/year, and the ratio (DFO used/Al removed) decreased to 150 g/25 mg after two years of DFO, though considerable tissue deposits persisted in the patient who died after 3 1/2 years of treatment. Despite unexplained EEG worsening, neurological symptoms improved. Relapses, however, occurred after many years of DFO. Bone status improvement, at least in parathyroidectomised patients, proved to be only partial and time-related. The therapeutic effectiveness of DFO in these patients seemed to be exhausted after two years even if Al deposits had not vanished.

Adult↗

The production of platelet-activating factor during hemodialysis.

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 (greater than 50% of basal values at 15 min), C3a des Arg generation (greater than 500% at 5 min), and plasma levels of the elastase-alpha 1-proteinase inhibitor complex (greater than 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 less than 0.05) from those observed with CU and PC membranes.

Cell Aggregation↗

Prevention and treatment of aluminum overload in uremic patients: long-term results.

The authors evaluate the efficacy of a protocol of prevention and treatment of aluminum (Al) overload in RDT patients during a 7-year period (from 1981, 164 patients, to 1987, 161 patients). Al in dialysate solutions was always less than 25 micrograms/l. Baseline Al levels greater than 100 micrograms/l were found in 22% of patients in 1981 but in none in 1987, while the percentage of values less than 60 micrograms/l increased from 55 to 91%. DFO tests were positive in 54% and 7% of cases in 1981 and 1987, respectively. A clinical diagnosis of Al intoxication was performed in 6 patients in 1981, and no further cases were diagnosed later. DFO treatment (50 mg/kg once a week) was employed preventively in 31 patients owing to positive DFO-tests, and in the 6 Al-intoxicated patients therapeutically. In the former patients none developed clinical intoxication. In the latter group clinical improvement was only temporary in the three parathyroidectomized patients. Al hydroxide [Al(OH)3] as a phosphate binder was tapered off in 1981 and substituted by Al-free chelants. In 1987, 66% of patients were given CaCO3 or Mg (OH)2 alone or in association, while 34% still needed Al(OH)3, although at low dosages (less than 2 g/day). The conclusion is that such a protocol is able to prevent and to treat cases of Al intoxication, albeit only partially.

Adult↗

Ultrafiltration in the treatment of refractory congestive heart failure.

Artificial subtraction of fluids and solutes was evaluated in the course of acute and chronic heart failure when it became refractory to standard intensive medical treatment. A group of 19 patients (mean age 57 years), 9 with ischemic, 2 amyloidotic, 4 valvular, and 4 idiopathic cardiomyopathy, were treated. In 17 patients extracorporeal ultrafiltration (UF) by means of a polysulfonate ultrafilter was adopted along 125 sessions (105 assisted by a roller pump and 20 as a slow continuous ultrafiltrate). In two patients continuous peritoneal dialysis was adopted. In every case UF was well tolerated. Ultrafiltrate volumes ranged from 1680 to 3500 ml for every session with corresponding Na losses ranging from 194 to 434 mEq/session. Improved clinical and functional status with reduction of edema was observed in 17 of 19 patients. In 12 patients UF could be discontinued due to restored response to diuretics; 5 of these patients could subsequently undergo heart surgery (1 transplant, 3 valve replacement, 1 coronary bypass). The remaining 7 patients survived on medical therapy alone for an average of 228 days. In 7 of 19 cases, UF could not be discontinued, and these patients died after an average of 23 days of treatment. In conclusion, UF proved to be effective in eliminating salt-fluid overload and restoring response to medical treatment. Patients who are potential surgical candidates seem to be the most suitable for UF.

Adult↗

[A possible role of magnetic resonance in the follow-up of renal transplants].

The authors discuss the possible role of Magnetic Resonance Imaging (MRI) in the follow-up of renal transplants. Its diagnostic accuracy is compared with Ultrasounds (US), which is considered the method of choice in postoperative monitoring of renal transplants. Thirty-two patients (transplant life ranging from 5 days to 37 months) were examined in the same day with both MRI and US. Sonographic evaluation is based on a group of signs related to renal alterations and unanimously ascertained; the identification of MR patterns of normally functioning kidney or renal rejection might give way to more extensive clinical applications of the method, with the advantages of multiplanarity and no X-ray use. MR diagnostic accuracy in the diagnosis of normally functioning transplant or renal rejection was 82.7% (vs. US: 68.9%); even though specificity was the same (84.6%). MRI had higher sensibility than US (82.25% vs. 656.25%). MRI is more sensitive in demonstrating renal pathology in transplanted kidneys, and its diagnostic accuracy is superior. Still, US must be considered the methodology of choice in instrumental research when there is a clinical suspicion of renal rejection, due to its sufficient diagnostic accuracy, to its being easy to perform in continuous follow-up, to its low cost and to the short execution time. MRI is nevertheless suggested in the follow-up of renal transplants both in questionable cases and when biopsy cannot be performed.

Adolescent↗

In vitro complement-independent activation of human neutrophils by hemodialysis membranes: role of the net electric charge.

Polymethylmethacrylate (PMMA) membranes with different net electric charges and percentage water contents (anionic 71%, neutral 70%, cationic 75%) were evaluated for their ability to stimulate plasma-free human polymorphonuclear neutrophils (PMN), and compared for potency to cuprophan (Cu), already described as being a potent trigger of PMN. The release of lysozyme, beta-glucuronidase, lactic dehydrogenase (LDH), and the generation of a platelet aggregating activity were studied in the supernatants from plasma-free human PMN incubated with different membranes. The PMN intracellular content of neutrophil cationic proteins (NCP), elastase, and cathepsin G were also studied by immunofluorescence using specific antisera on smears of PMN before and after incubation with each membrane. Only cationic, but not anionic or neutral PMMA induced a marked release of lysozyme (range 20-25% of the sonicated control, assumed as 100%), and beta-glucuronidase (40-43%), and marked depletion of the intracellular content of NCP, elastase, and cathepsin G, suggesting a degranulation process. Platelet aggregating activity was generated and referred to the release of platelet activating factor (PAF) only in the supernatants from PMN incubated with cationic, but not with anionic, or neutral PMMA membranes. These results indicate that modification of the net electric charge can per se turn PMMA, commonly recognized as inert, into a material with marked PMN activating effects, comparable to those of Cu, a highly reactive polymer.

Cations↗

Patients with chronic renal failure are not at a risk of developing chronic peptic ulcers.

This study reports the endoscopic and histological aspects of gastrointestinal mucosa in a consecutive series of 249 patients with chronic renal failure on conservative hemodialysis, who were awaiting renal transplantation. At endoscopy the mucosa was normal in 54.2% of the cases and revealed gross inflammatory changes in 34.1%. Duodenal ulcers were found in 11.2% of patients with only one gastric ulcer. Of the 28 duodenal ulcers, 16 were active and 12 inactive lesions. Gastric biopsies sampled from 44 non-ulcer patients showed signs of chronic gastritis in 29.6%, atrophic gastritis in 18.2, and reported normal in 52.3% of the cases. The above findings were not affected by the ages of patients or by the total duration of hemodialysis treatment. It is concluded that patients with chronic renal failure share the same risk of developing chronic peptic ulcers as the general population. Moreover, the overall endoscopic and histological appearance of the mucosa in these patients appears not to differ from data reported in the general population.

Adult↗

Cimetidine does not influence cellular immunity in patients with chronic renal insufficiency.

Numerical and functional markers of peripheral lymphocytes were adopted to study the influence of cimetidine on the immune response in immunocom-promized patients. Twenty-three patients on regular dialysis treatment, who had been given cimetidine (400 mg daily) for peptic ulcer, were studied during a follow-up of 3 months. Thirty healthy people served as controls for the study of the immunological parameters, i.e. DNCB and PPD skin tests, E-rosetting assays, monoclonal antibodies to T-cells, membrane immunoglobulins for the B-cells, serum immunoglobulins and complement. Before therapy was started CMI was impaired in all patients, with a significant reduction in the E-rosette count (P less than 0.01) and depressed DTH (DNCB, PPD). The number of active E-rosettes and OKT4 subsets increased slightly during the period of treatment, though this finding was not confirmed by functional in vivo tests. No change was observed in the B-lymphocyte count and in serum immunoglobulins or complement. The fact that treatment with cimetidine does not seem to influence the immune response in patients on RDT, may suggest that this therapy does not restore the principal immunopathological disorder of these patients, and further justifies its use in patients awaiting renal transplantation or in those who have been given transplant.

Adult↗

Effect of prostacyclin (PGI2) on immune-complex-induced neutropenia.

This study reports the results of in vitro and in vivo investigations on the effect of prostacyclin (PGI2) on polymorphonuclear neutrophils (PMN) challenged with immune complexes (IC). In vitro, PGI2 does not affect the interaction of IC with PMN membrane receptors, but prevents the ensuing PMN aggregation and secretion of platelet-activating factor, a lipid mediator responsible for immune-induced PMN aggregation. In vivo, the infusion of PGI2 in New Zealand white rabbits injected with IC prevents IC-induced neutropenia and thrombocytopenia as well as the embolization of PMN into the pulmonary peripheral capillary network. These results suggest a physiological role for PGI2 in modulating the interaction between IC and PMN.

Agranulocytosis↗