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Biomedical subjects

A Pacitti

Publications and source records attributed to A Pacitti.

At least 37 records · Page 2Linked to original sources

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↗

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↗

Heparin transfer across the rabbit peritoneal membrane.

Variable quantities of heparin have been proposed to avoid intraperitoneal clotting during peritoneal dialysis without the risk of systemic effects, because heparin is presumed to be incapable of passing through the peritoneal membrane. This study set out to verify this assumption by using labeled heparin in experimental dialysis in 7 New Zealand white rabbits. Heparin was labeled with 99mTc. Labeling quality, assessed by two chromatographic checks, showed less than 5% of free pertechnetate. Chromatographic determinations showed more than 95 and 80% of labeled heparin in inflow and outflow dialysates and in blood samples respectively. Following sodium thiopental anesthesia, animals underwent three protocols: a single 15 min cycle of time diffusion with heparin 500 U/l (A), 6 successive 15 min cycles with heparin 500 U/l (B), and a single 3 h cycle with heparin 2,500 U/l (C). Labeled heparin was found in blood organs and urine in variable percentages. The total amount of recovered radioactivity ranged from 1.5% (A) to 20% (C) of that introduced. It may be concluded that heparin passes through the peritoneum according to some law dependent on the amount used and the diffusion time.

Animals↗

Hypervitaminosis B12 in maintenance hemodialysis patients receiving massive supplementation of vitamin B12.

We have administered routinely a multivitamin preparation containing a megadose of B12 to 106 hemodialysis patients after dialysis treatments. We found that these patients had very high levels of serum vitamin B12 which returned to original values only after a period of three years after stopping the vitamin. Discontinuing therapy had no effect on hemoglobin, mean erythrocyte corpuscular volume, or motor nerve conduction velocity. It is not known whether maintaining a prolonged high level of vitamin B12 is harmful. However, animal and epidemiologic studies have suggested that both cobalamin and cobalt may be potentially toxic. In view of the absence of demonstrable benefit and the possible risk of toxicity, we believe that the use of such megadose vitamin compounds in dialysis patients should be re-evaluated.

Adult↗

Hemofiltration in diabetic uremic patients.

The increasing number of Diabetic Uremic Patients (DUP) starting the substitutive treatment (ST) constitutes a difficult and often disappointing problem in terms of efforts, clinical results and side-effects. While treatment of these patients by C.A.P.D. is well documented, the adoption of Hemofiltration (HF), has been, up to now scarcely considered. In order to define the potentialities of a HF policy in the treatment of these patients, data from 6 DUP treated with postdilutional HF for a 10.6 months/patient period were collected on a multi-center basis and retrospectively examined. Good results were achieved in terms of vascular stability, control of arterial hypertension and of retinopathy, clinical complications and hospitalization rate. Although C.A.P.D. may represent a first choice treatment for DUP with residual function, satisfactory glicemic control, difficult blood access and a motivation to full autonomization, HF may constitute a logical alternative when C.A.P.D. should be unmanageable (visus impairment, history of repeated peritonitis and dismetabolism, considerable weight gain): an integration of HF and C.A.P.D. can assure PDU with a continuative treatment.

Blood↗

Impaired fibrinolysis in uremia: partial and variable correction by four different dialysis regimes.

In addition to a hemorrhagic diathesis, uremia is accompanied by a clotting tendency, caused by a marked fall in fibrinolytic capacity. Measurement of lysis time of whole blood diluted with phosphate and acetate buffers and of euglobulin lysis times showed that accumulation of inhibitors is primarily responsible. These probably belong to the class of small molecules abnormally retained in uremia. Hemodialysis (HD) offers the best method of correction, mainly because of better elimination of these inhibitors. In contrast, hemofiltration (HF) and, particularly, intermittent peritoneal dialysis (IPD) are much less effective. In IPD, protein loss via the peritoneum is also responsible for a loss of fibrinolytic activators, so that fibrinolysis becomes even poorer, exposing the patient to an increased risk of vascular complications.

Adult↗

Heparin is unable to prevent contact activation by three different membranes.

In spite of the anticoagulant activity of heparin platelet deposition and contact activation of coagulation occurs during dialysis. We have studied platelet counts, fibrinogen, platelet factor 4, beta-thromboglobulin, thromboxane B2, FRA, C3d and kallikrein values, whole blood and euglobulin lysis times and membrane areas in haemodialysis using cuprophan and cellulose acetate and in haemofiltration with polyacrilonitrile. Deposits on all the three membranes included leucocytes, platelets and fibrin. The coagulation and fibrinolytic systems are activated more intensively with cellulose acetate and more prolongedly with polyacrilonitrile. Platelet factor 4 and beta-thromboglobulin increases suggest platelet activation, only partially dependent on arachidonic acid-mediated pathway as thromboxane B2 is not increased. The complement system is activated whereas serum kallikrein does not alter, suggesting that platelets rather than factor XII are crucial in contact activation.

Adolescent↗