The hematopoietic system in renal failure.
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Biomedical subjects
Publications and source records attributed to V Cambi.
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Acute renal failure (ARF) is a common manifestation of a septic condition which very often complicates surgical and traumatic events. The release of endotoxin, a lipopolysaccharide (LPS) from the cell wall of Gram-negative bacteria, and subsequently of numerous host mediators, is the initiating event of sepsis syndrome and eventually of septic shock. Particularly interesting is the observation that not only endotoxins but also Staphylococcus aureus which does not produce endotoxins induce the same cardiovascular changes of septic shock. The main aspect of septic shock is the inadequate oxygen supply to the body tissues. However, despite the documented myocardial depression in the course of septic shock, myocardial ischaemia is not to be considered a contributing factor, and the coronary blood flow is normal or even increased. Protein hypercatabolism can be at best only limited; in any case the optimal protein-sparing effect was observed with 1.5 g/kg proteins. Recently monoclonal antibodies to endotoxin core glycolipid have been developed; they are: (a) E5, a murine IgM anti-lipid A monoclonal antibody; (b) HA-1A, a human monoclonal antibody to endotoxin core glycolipid. In conclusion, hypercatabolic septic patients should be managed in an intensive care environment where a continuous monitoring of fluids, electrolytes, and acid-base disorders can be achieved. Surgical search of septic foci, and wide-spectrum antibiotic therapy are fundamental measures to combat cytokine and vasodilator production which impair tissue perfusion and create the premise of a shock status complicated by lactic acidosis. Dialysis treatment is a further complementary but fundamental approach that allows a large fluid and nutritional intake and a continuous correction of electrolyte and acid-base disorders.
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In the present study we evaluated spontaneous and stimulated adherence of human monocytes to regenerated cellulose and polyacrylonitrile (AN69) membranes. Spontaneous adherence at 60 min was significantly higher for regenerated cellulose (28 +/- 2%, P < 0.001) than for AN69 (11 +/- 2) membranes. Stimuli such as bacterial lipopolysaccharide, TNF alpha, interleukin-1 and -6 as well as platelet-activating factor, but not IL-4, significantly enhanced adherence at 60 min to AN69 (28 to 30%). In contrast, adherence was not further inducible in the presence of regenerated cellulose. Both spontaneous and cytokine/bacterial lipopolysaccharide-stimulated adherence were significantly reduced by SDZ-63072, a specific platelet-activating factor receptor antagonist. This difference in sensitivity of monocyte adherence reflects probably the intrinsic ability of regenerated cellulose to provide maximal spontaneous monocyte adhesion. These data suggest that PAF may act as an adherence mediator. This is in line with the ability of regenerated cellulose to directly stimulate monocytes to synthesize platelet-activating factor and with the ability of cytokines and bacterial lipopolysaccharide to stimulate its synthesis. Although AN69 has a low adherence potential, bacterial lipopolysaccharide or cytokines may blunt the biocompatibility of this membrane.
A complex array of inflammatory mediators are generated as a consequence of blood contact with hemodialysis (HD) membranes. Beside complement activation, other mediators are involved in cell activation, and are thought possibly to be responsible for early and long-term multiple changes in immunity infection, hypercatabolism, beta 2-microglobulin generation and hemostatic mechanisms. Previous studies from our laboratories have established platelet activating factor (PAF) as one of the mediators generated by complement-dependent or independent mechanisms of cell interaction with hemodialysis membranes. Recent studies on the production of PAF from endotoxin-primed polymorphonuclear neutrophils in a closed miniaturized circuit, and on the effect of PAF in mediating endotoxin- and cytokine-induced leukocyte adherence to HD membranes, highlight so far undescribed new roles of this mediator in biocompatibility.
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BK-PMMA 2.1 m2 surface dialysers were used in vivo and in vitro for evaluation of their capacity for beta 2-M removal by both adsorption and elimination through the membrane. As expected, in vivo, beta 2-M plasma concentrations were more effectively reduced when the dialyser was used in haemofiltration, rather than in haemodialysis. However, the mass recovered in the ultrafiltrate could not account for the observed difference in beta 2-M removal. In vitro tests demonstrated that membrane adsorption of beta 2-M is greater when the dialyser is used in convection than in diffusion. Therefore, the greater beta 2-M removal during haemofiltration depends on both increased adsorption and membrane elimination by convection. Thanks to adsorption, beta 2-M removal by haemodialysis was greater than for other synthetic membranes, but was insufficient to obtain beta 2-M removal corresponding to the estimated generation.
The pharmacokinetics of iopamidol 370 (Iopamiro), a non-ionic water soluble organic iodine compound, were studied in adults with different degrees of chronic renal failure and in healthy volunteers. After 50 ml were administered i.v., plasma and urine levels were determined. The main pharmacokinetic parameters were calculated on the basis of bi-compartimental open model. There were significant differences from healthy volunteers in t1/2 beta, which increased with the degree of renal failure as the clearance values decreased. t1/2 beta was equal to 1.67 h in healthy volunteers, 4.24 h in patients with mild renal failure and 10.03 h in patients with severe renal failure. The clearance decreased as follows: 0.11 (l/h kg) in healthy volunteers, 0.06 (l/h kg) in patients with mild renal failure and 0.02 (l/h kg) in patients with severe renal failure. No significant differences were found in distribution volume values nor in t1/2 alpha.
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High efficiency hemofiltration (HF) was carried out for 9 months in 6 patients on hemodialysis (HD). Comparative studies on carbohydrate metabolism and 500- to 1,500-dalton serum solute concentrations were performed during HD and HF. After 5 months of HF, intravenous glucose tolerance tests showed an improved peripheral glucose utilization, with unchanged insulin secretion. Larger solute concentrations, measured by gel chromatography, simultaneously dropped in serum suggesting that HF removes some toxic substances that inhibit peripheral insulin action. After 9 months of HF, an unexpected increase in the larger solute concentration coincided with an impaired glucose tolerance, stressing the probable toxic rule of such solutes. Changes in other glucoregulatory hormone secretions were not unequivocal. On account of the later increase in 500- to 1,500-dalton solute concentrations, HF failed to prevent larger toxic molecules accumulating in uremic sera.
Postdilution haemofiltration is a treatment indicated for patients who are unable to tolerate standard dialysis. However, its duration is uncomfortably prolonged in cases of low blood flow from the vascular access. In a predilution mode greater clearance rates can be reached even if a greater amount of sterile and pyrogen-free solutions are required. Although an in-line solution-producing system lowers the cost, theoretical calculations indicate that a predilution mode is not advantageous, in terms of the amount of infused solutions, if urea clearances greater than 150 ml/min at 300 ml/min blood flow are required. Theoretically, the combination of predilution and postdilution is the best system to utilise relatively small amounts of sterile solution in order to enhance treatment efficiency at low blood flow. However, the predilution mode may ultimately be preferable because of easier utilisation of the hardware. The results of clinical application of pre-postdilution haemofiltration indicate that at a 400 ml/min blood flow, a urea clearance of more than 220 ml/min can be obtained, and the duration of treatment can be reduced to only 3 h in the majority of patients.
A case of partially reversible chronic renal failure due to long-term NSAID use is discussed. An analysis of this and similar cases recently reported indicates many similarities between chronic NSAID nephropathy and analgesic nephropathy.
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Ten patients of a population of 319 on chronic intermittent treatment with Cuprophan dialyzers have undergone surgery for carpal tunnel syndrome (CTS). Since 1971 the dialysis schedule for all patients has been 4 m2/h three times per week. All patients were anuric. The operated patients represent 16% of the total population. In comparison with a dialysis population in other units described in the literature (12), 8 m2/h performed three times per week, with similar dialysis aging and a CTS incidence of 47%, it appears that the duration of the dialysis session per se increases the frequency of CTS and leads to the problem of the consequences of blood membrane interaction.
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