The patient with acute renal failure and nondilated urinary tract.
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Biomedical subjects
Publications and source records attributed to A Pacitti.
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Availability of a proper vascular access is a basic condition for a proper extracorporeal replacement in end-stage chronic renal failure. However, biological factors, management and other problems, may variously condition their middle-long term survival. Therefore, personal experience of over 25 years has been critically reviewed in order to obtain useful information. In particular "hard" situations necessitating complex procedures have been examined but, if possible, preserving the peripherical vascular features.
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The increase in the incidence of elderly patients starting dialysis has been as sharp, during the 1980s-1990s, as an epidemic (+70%, +150% in different settings). According to this study, performed in Piemonte, northern Italy, the process is still ongoing. During the period 1981-93, according to the Regional Registry of Dialysis and Transplantation (RPDT: data on 100% of centres and patients), the cohort on treatment increased by 79.5% and the annual incidence by 48.3%; the increase is limited to older people and is greater in males. Nephroangiosclerosis/ischaemic renal disease and diabetes mellitus are the main diagnoses. Since the increase of elderly patients is still ongoing, forecasts are difficult; according to a computer simulation, a plateau of patients on treatment is reached only if incidence is stabilized, While it is impossible to exclude a decrease in hidden selection or an increase in referral, complex modifications at the overall population level are presumably at the basis or the increase of elderly patients on dialysis. Despite the increase in average age, however, survival improved throughout the period; this confirms the interest towards the open dialysis system adopted in Piemonte, which is characterized by easy shifts among treatments and by the widespread use of high tolerance techniques.
A computerized system, structured by 4 different models concerning urea depuration, and bicarbonate and sodium handling in acetate-free hemodiafiltration has been conceived for integrated use covering each step of the therapeutic cycle, from a) the prescription of the session to b) its delivery, up to c) the dose-response analysis: the system, now fully developed for the bicarbonate cycle, covers both working areas; the medical one, with a program implemented on a Personal Computer, called Skipper which deals with steps a) and c), and the nursing area, with a program built into the dialytic equipment software. The Skipper program supports the prescription step (a) testing the session schedule by bicarbonate, sodium and urea kinetics. The dialytic equipment, (step(b)) using a different program, on the basis of the scheduled parameters memorizes the end-session plasma bicarbonate level and reacts to any modifications of the parameters regarding blood flow and fluid reinfusion flow suggesting opposite changes in order to reach the scheduled results. Finally (step (c)), the Skipper system statistically evaluates the observed end session bicarbonate plasma level with an expected value with upper and lower confidence bounds obtained by a multiple regression analysis performed on a large population of patients.
The cytoplasmic region of human CD45 corresponding to residues 584-1281 was inserted downstream of the alcohol dehydrogenase promoter and transfected into a haploid strain of yeast. Expression of recombinant CD45 in yeast reached as high as 5% of the soluble protein. Following removal of cellular debris by centrifugation and an ammonium sulfate precipitation step, the enzyme was purified using phenyl-Sepharose chromatography, preparative gel filtration, Mono Q anion exchange chromatography and a final analytical gel filtration step. Enzymatically active material with a purity of > or = 98% was obtained with a yield approaching 50%. The final product gave a Km of 5.5 mM and a Vmax of 87.5 U/mg with p-nitrophenylphosphate and a Km and Vmax of 0.167 mM and 185 U/mg, respectively, with a phosphotyrosine peptide. The native enzyme purified from Jurkat cells showed comparable Kms with both substrates to the recombinant enzyme but displayed substantially lower Vmax values for both substrates.
Different beta 2-microglobulin (beta 2m) serum profiles have been related to dialytic membranes, mass transport and/or patient immune stimulation. Eight patients were followed by cycles of four sessions: hemodialysis (HD), hemodiafiltration (HDF), acetate-free HDF (AFH), hemofiltration (HF) by filters on synthetic membranes (polysulphone = 4; methylmethacrylate = 4); pre- (A) and post- (B) measurements in the fourth session, and at the start of the next one (C), beta 2m lipopolysaccharide content of the fluids (LPS), and monocytes in vitro and spontaneous production of interleukins (IL); IL-1-IL-6 and tumor necrosis factor (TNF) were measured. In HD, beta 2m (mg/liter), corrected for ECV distribution, did not change (A = 36.5 +/- 10, B = 37 +/- 9, C = 36.4 +/- 9.7). In HDF, lower basal beta 2m (P < 0.001; A = 26.5 +/- 9) still decreased (B = 9.13 +/- 6.2), boosting subsequently to C = 21.6 +/- 14, as in AFH (A = 24.5 +/- 7, B = 11.2 +/- 2, C = 25.3 +/- 9) and in HF (A = 26.6 +/- 7; B = 8.5 +/- 4; C = 25.6 +/- 11). LPS (EU/ml) decreased (P < 0.001) from HD fluids (0.41 +/- 0.1) to HDF (0.28 +/- 0.1), AFH (0.15 +/- 0.1) and HF (0.04 +/- 0.05) but IL-1 and IL-6 were found in greater concentrations in HDF and AFH versus HD and HF, probably due to back-filtration. Beta 2m in different modes of dialytic treatments seem better correlated with the amount of convective transport rather than with the selected markers of immune stimulation.
We treated a patient with refractory biventricular heart failure, dilutional hyponatremia and prerenal azotemia, by means of ultrafiltration. After ultrafiltration, gas exchange and cardiac output improved, with concomitant reduction of systemic and pulmonary vascular resistances. Despite a decrease of right atrial and wedge pressure, atrial natriuretic factor rose and plasma renin activity decreased.
Variable tissue overloading can alter the removal rate of iron and aluminum from uremics. Owing to its higher affinity to deferoxamine (DFO) and higher plasma concentrations, Fe could impair Al removal in cases of simultaneous body burden. Fe and Al plasma kinetics and mass transfer were therefore studied in 12 uremic patients with different Fe and Al status: six with normal ferritin levels (less than 400 micrograms/L [ng/mL]), and Al 1.4 to 4.7 mumol/L (40 to 131 micrograms/L) (group A); six with increased ferritin (greater than 2,000 micrograms/L), and Al 1.7 to 17 mumol/L (47 to 476 micrograms/L) (group B). DFO (40 and 80 mg/kg in a random sequence) was administered once a week during the first hour of the first hemofiltration (HF). The results show that in both groups and with both DFO doses, maximum Fe and Al mass transfer was achieved in the first and second HF, respectively. The 80-mg/kg dose of DFO significantly raised Al mass transfer in both groups, whereas Fe mass transfer was only slightly affected. Even though plasma Fe levels were almost always higher than Al, Al mass transfer eventually exceeded that of Fe, in both Fe-normal and Fe-overload patients. The bias towards Al in mass transfer was enhanced in both groups in the second HF, and at the higher DFO doses. Thus, DFO once a week reduced Fe loss to less than 30 mumol/wk in patients with normal ferritin levels. In both Fe and Al overloaded patients, Al can be removed, and Al mass transfer may often exceed Fe mass transfer, depending on the degree of tissue burden, the time from DFO infusion, and the DFO dose.
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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.
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.
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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.
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.
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.
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.