The analysis of flow distribution in cartridges designed for hemoperfusion is extremely important. Taking advantage of a new imaging technique, based on the analysis of a helical scanner-generated imaging sequence, we studied the blood flow distribution in a series of cartridges for extracorporeal removal of endotoxin. Cartridges with improved design were compared to cartridges with a standard design. The improved design consists in a different structure of the holes of the distributor of the flow within the adsorbent unit. Cartridges were studied in vitro with human blood from voluntary donors at blood flows of 100 and 250 ml/min. The progression of density in specific regions of interest (ROI) was analyzed to detect the distribution of the dye injected in the blood circuit. The study demonstrates that both at 100 ml/min and at 250 ml/min of blood flow, the progression of flow appears more homogeneous in the devices with improved design. In detail, the flow distribution measured by the incremental density values detected in the ROIs of the proximal comers (close to the arterial port) and in the ROIs of the central region of the device (close to the inner wall of the case) displays a significant difference between the standard and the improved device. The ROIs studied in the standard devices display a slower increase in density and significantly lower absolute values expressed in Hounsfield units. The experimental method utilized to analyze flow distribution seems to represent an important means to study the performance and design of this type of device.

Adsorption↗

PubMed2001

Choosing new adsorbents for endogenous ultrapure infusion fluid: performances, safety and flow distribution.

Adsorption may notably contribute to the removal of uremic toxins and to the efficiency of hemodialysis. We examined different uncoated stationary matrixes, charcoals and synthetic resins to establish their adsorptive capacities in relation to low (urea, creatinine) and high molecular weight (beta2-microglobulin, myoglobin) compounds in in vitro conditions (steady state and flow-through) using isotonic solutions or uremic ultrafiltrate. Trace metal, particle release analyses and scanning electron microscopy of different adsorbents were performed. Dynamic flow-distribution studies were made using 99Technetium and analysing the different regions of interest by single head gamma-camera. We show that adsorbents may differ greatly as to their adsorptive capacity depending on flow rate, nature, and total mass of the compounds to be removed from the ultrafiltrate. These studies suggest a methodological approach for screening stationary matrixes for possible application in hemodialysis.

Adsorption↗

PubMed2000

Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial.

BACKGROUND: Continuous veno-venous haemofiltration is increasingly used to treat acute renal failure in critically ill patients, but a clear definition of an adequate treatment dose has not been established. We undertook a prospective randomised study of the impact different ultrafiltration doses in continuous renal replacement therapy on survival. METHODS: We enrolled 425 patients, with a mean age of 61 years, in intensive care who had acute renal failure. Patients were randomly assigned ultrafiltration at 20 mL h(-1) kg(-1) (group 1, n=146), 35 mL h(-1) kg(-1) (group 2, n=139), or 45 mL h(-1) kg(-1) (group 3, n=140). The primary endpoint was survival at 15 days after stopping haemofiltration. We also assessed recovery of renal function and frequency of complications during treatment. Analysis was by intention to treat. RESULTS: Survival in group 1 was significantly lower than in groups 2 (p=0.0007) and 3 (p=0.0013). Survival in groups 2 and 3 did not differ significantly (p=0.87). Adjustment for possible confounding factors did not change the pattern of differences among the groups. Survivors in all groups had lower concentrations of blood urea nitrogen before continuous haemofiltration was started than non-survivors. 95%, 92%, and 90% of survivors in groups 1, 2, and 3, respectively, had full recovery of renal function. The frequency of complications was similarly low in all groups. INTERPRETATION: Mortality among these critically ill patients was high, but increase in the rate of ultrafiltration improved survival significantly. We recommend that ultrafiltration should be prescribed according to patient's bodyweight and should reach at least 35 mL h(-1) kg(-1).

APACHE↗

PubMed2000

Cutting edge: a role for CD1 in the pathogenesis of lupus in NZB/NZW mice.

Since anti-CD1 TCR transgenic T cells can activate syngeneic B cells via CD1 to secrete IgM and IgG and induce lupus in BALB/c mice, we studied the role of CD1 in the pathogenesis of lupus in NZB/NZW mice. Approximately 20% of B cells from the spleens of NZB/NZW mice expressed high levels of CD1 (CD1high B cells). The latter subset spontaneously produced large amounts of IgM anti-dsDNA Abs in vitro that was up to 25-fold higher than that of residual CD1int/low B cells. T cells in the NZB/NZW spleen proliferated vigorously to the CD1-transfected A20 B cell line, but not to the parent line. Treatment of NZB/NZW mice with anti-CD1 mAbs ameliorated the development of lupus. These results suggest that the CD1high B cells and their progeny are a major source of autoantibody production, and activation of B cells via CD1 may play an important role in the pathogenesis of lupus.

Animals↗

PubMed2000

Bioethical issues related to continuous renal replacement therapy in intensive care patients.

OBJECTIVE: To examine the ethical approach of intensivists and nephrologists to continuous renal replacement therapy (CRRT). DESIGN: A questionnaire. SETTING: The First International Course on Critical Care Nephrology. PARTICIPANTS: The participants in the course (around 500). RESULTS: Most participants think that establishing ethical criteria for managing CRRT is a medical task, as clinicians have adequate criteria for defining futility. However, many responders would grant the request of starting futile CRRT or would maintain it if requested by the family. Only 55% believe that informed consent is necessary for initiating CRRT; one out of four would start or maintain unwanted life-saving CRRT. In case of lack of equipment, the majority would select the patients, excluding the worst one or on a "first-come, first-served" basis. Withholding and withdrawing are regarded differently by most responders. Again, most think that every vital support should be withdrawn when futile, but practical and psychological aspects still influence the final decision. Responders think that ethics critical care committees can help in the management of ethical problems in ICU. CONCLUSIONS: Our results show that several ethical questions are still unsolved and that practical and psychological aspects of the treatment process can be stronger than bioethical principles.

Attitude of Health Personnel↗

PubMed2000

Analysis of CIITA encoding AIR-1 gene promoters in insulin-dependent diabetes mellitus and rheumatoid arthritis patients from the northeast of Italy: absence of sequence variability.

Qualitative and/or quantitative alterations in the expression of the MHC class II molecules affect the onset and maintenance of the immune response and may be the basis of a wide variety of disease states, such as autoimmunity and immunodeficiency.CIITA is a major physiological regulator of the expression of MHC class II genes. The availability of CIITA ap- pears generally essential for MHC class II gene expression, and hence its own transcriptional regulatory mechanisms result of fundamental importance for a correct homeostasis of the immune response. Therefore, it is possible to hypothesize that variability at the CIITA-encoding locus, AIR-1, could constitute an additional source of susceptible traits to autoimmune diseases. Mutations at AIR-1/CIITA promoters could modulate expression of CIITA. Variations in CIITA expression could influence the qualitative and quantitative expression of MHC class II molecules at cell surface. We have analyzed sequence variation at AIR-1/CIITA promoters by PCR-SSCP in 23 IDDM and 30 RA patients compared to a sample of 19 unaffected normal controls and 16 unaffected IDDM family members, for a total of 88 Caucasian subjects from the Northeast of Italy. No sequence difference was found at the four AIR-1/CIITA promoters between autoimmune patients and normal controls. Moreover, the promoters resulted invariant within the entire group of 88 subjects analyzed, comprising patients and controls. This finding suggests a possible selective advantage in maintaining CIITA upstream regulatory sequences invariant.

Arthritis, Rheumatoid↗

PubMed2000

Expression of myelin basic protein (MBP) epitopes in human non-neural cells revealed by two anti-MBP IgM monoclonal antibodies.

Two monoclonal antibodies (1H6.2 and 45.30) were raised against MBP purified from human brain under experimental conditions that allowed MBP to retain binding to surrounding myelin lipids (human lipid-bound MBP (hLB-MBP)). 1H6.2 and 45.30 MoAbs were selected on the basis of their different binding properties to: hLB-MBP, human lipid-free-MBP (hLF-MBP) and bovine lipid-free-MBP (bLF-MBP). Although the isotype of both MoAbs was IgM, their specificity, as tested in ELISA assays against chemical haptens and unrelated protein antigens, was restricted to MBP. 1H6.2 and 45.30 MoAbs stained MBP from human brain white matter tissue extracts, as well as bLF-MBP, in Western blot assays. Both MoAbs stained oligodendrocytes and myelin in immunohistochemical analysis of white matter from human brain. Tissue sections from human peripheral nerves were labelled by 1H6.2 only, however, demonstrating that the MoAbs recognize two different epitopes. Epitopes recognized by 1H6.2 and 45.30 MoAbs were also expressed by a wide array of human non-neural cells of either normal or pathological origin, as evidenced by cytofluorimetric assays. In particular, MBP epitopes (MEs) were expressed by lymphoid cells as well as by cells which play a pivotal role in immune homeostasis and in the immune response, such as thymic epithelial cells and professional antigen-presenting cells. Both MoAbs were efficiently internalized by cells from a human B cell line, suggesting trafficking of MEs along the endocytic pathways. These findings support hypotheses regarding the role of MEs expressed by non-neural cells in establishing self-tolerance and/or in triggering the immune response against MBP antigen.

3T3 Cells↗

PubMed2000

Impact of biofeedback-induced cardiovascular stability on hemodialysis tolerance and efficiency.

BACKGROUND: Hypotension is caused by a drop in blood volume during ultrafiltration, followed by vasoconstriction and reduced perfusion in some regions of the body. METHODS: We carried out a prospective controlled crossover study on 12 hypotension-prone patients with two different modalities: (A) acetate-free hemodiafiltration with standard ultrafiltration control, and (B) acetate-free hemodiafiltration with monitoring of blood volume and automatic biofeedback with machine-driven adjustments on ultrafiltration and dialysate conductivity. We measured urea Kt/V and equilibrated Kt/V (eKt/V), urea rebound, and urea removal. Hypotensive episodes and interventions were recorded. RESULTS: In group B, fewer hypotensive episodes were recorded (24 out of 72 in group B vs. 59 out of 72 in group A). Saline infusion was required in 57 cases in group A and 15 cases in group B. Urea Kt/V was 1.34 +/- 0.08 in group A and was 1.26 +/- 0.06 in group B; eKt/V was much higher in group B (1.12 +/- 0.05) than in group A (1.03 +/- 008). A significantly higher rebound was observed in group A (14.2 +/- 2.7%) compared with group B (6.4 +/- 2.3%). Discussion. A greater solute sequestration seems to occur during hemodialysis with hypotension. This results in lower eKt/V, enhanced postdialytic rebound, and lower solute removal. Higher efficiency can be observed when dialysis is carried out smoothly and cardiovascular stability is maintained. We conclude that new systems for blood volume monitoring and automatic biofeedback may not only reduce the number of hypotensive episodes during dialysis, but may also contribute to significantly increase the efficacy of the treatment.

Adult↗

PubMed2000

Effects of a reduced inner diameter of hollow fibers in hemodialyzers.

BACKGROUND: The clearance of middle molecules in high-flux hemodialyzers is due to the higher contribution of convection in the overall solute transport. Although net filtration can be maintained low by the machine control, internal filtration in the proximal part of the dialyzer remains high. The final fluid balance is achieved by significant amounts of backfiltration in the distal part of the dialyzer. To increase further middle molecule clearance (MMK), hemodiafiltration has been used. This technique, however, requires complex machines and large amounts of substitution fluid. We present a novel solution to increase the convective transport of middle molecules in high flux dialyzers without the need for substitution fluids. In particular, high-flux dialyzers with a reduced hollow fiber diameter are compared with standard dialyzers in terms of internal filtration and solute clearances. METHODS: Hemodialyzers with 175 micro inner diameter polysulfone fibers were compared with standard 200 micro polysulfone hollow fiber dialyzers. The study was carried out in vitro using a previously published method to measure internal filtration and backfiltration rates. The method is based on the detection by a gamma camera of segmental variations in concentration along the length of the dialyzer of a nondiffusable Tc99-labeled marker molecule injected in the blood in vitro circuit. At the same time, pressures were detected in the blood and dialysate compartment. The system was operated at zero net filtration maintaining volumetrically constant both dialysate and blood circuits. In vivo clearances were also measured for solutes with different molecular weight. RESULTS: The pressure drop in the blood compartment at 300 mL/min of blood flow passed from 112 to 159 mm Hg. At the same blood flow, the internal filtration-backfiltration rates increased from 23. 1 to 48.2 mL/min. This resulted in a significant increase of in vivo in clearances of vitamin B12 and inulin of more than 30%. Urea, creatinine, and phosphate clearance did not display any change. CONCLUSIONS: A reduction of the inner diameter of the hollow fibers in high-flux dialyzers may result in a significant increase of the blood compartment resistance. In turn, this results in increased rates of internal filtration and backfiltration. The practical effect in clinical dialysis is demonstrated on middle molecules. While, in fact, the clearances for small solutes such as urea and creatinine are not affected, the clearances of larger solutes such as vitamin B12 or inulin increase significantly (P < 0.01).

Biocompatible Materials↗

PubMed2000

Hemodiafiltration with online regeneration of the ultrafiltrate.

The concept of regeneration of dialysis fluids and of ultrafiltrate in particular has been recently revisited. Hemodiafiltration with online regeneration of the ultrafiltrate allows the concomitant infusion of sodium, calcium, and bicarbonate. Here, we studied the adsorptive characteristics of an integrated two-step sorbent system relative to different solutes present in the ultrafiltrate: sodium, calcium, phosphate, bicarbonate, uric acid, creatinine, and beta2-microglobulin. In vitro studies were performed in order to differentiate the relative roles for each sorbent (mineral-activated charcoal or hydrophobic resin) in adsorbing a given solute. Ex vivo studies were performed in order to evaluate the presence of cytokines (interleukin-1 beta and tumor necrosis factor-alpha), of cytokine (interleukin-1 beta and tumor necrosis factor-alpha)-inducing activities, and of the cytokine release in response to exogenous bacterial lipopolysaccharide by normal whole blood incubated with ultrafiltrate samples obtained at 15, 120, and 240 minutes after the start of treatment. The results of the present studies show the presence of immunomodulatory substances in the ultrafiltrate and the significant (P < 0.01) increase in the lipopolysaccharide-induced release of both interleukin-1 beta and tumor necrosis factor-alpha. The biological relevance of the ultrafiltrate and the possible relevance of the online, endogenous reinfusion are discussed.

Adsorption↗

PubMed2000

Adsorption in sepsis.

The pathophysiology of sepsis offers a highly complicated scenario. In sepsis, endotoxin or other gram-positive-derived products induce a complex and dynamic cellular response, giving rise to several mediators known to be relevant in the pathogenesis of septic shock such as specific mediators, substances responsible for up- or down-regulation of cytokine receptors and cytokine antagonists, inactivators of translational or transductional pathways, and precursor molecules. In this review, we delve into some new concepts stemming up from the use of sorbents in continuous plasma filtration. Nonspecific simultaneous removal of several mediators of the inflammatory cascade have led to improved outcomes in animal models of septic shock and to improved hemodynamics in a pilot clinical study. It seems of great importance to explore all possible treatment techniques that may have a direct impact on circulating mediators of sepsis and that also may interfere with the imbalance between proinflammatory and anti-inflammatory substances in the critically ill patient with multiple organ failure. In this view, the application of sorbents appears to open new and interesting therapeutic options. The search for innovative treatments specifically targeted to the special needs of the critically ill patients seems therefore more important than the attempt to adjust concepts and technologies that are normally applied to patients with chronic renal failure.

Adsorption↗

PubMed2000

New developments in hemodialyzers.

Explore the source record for details and available documents.

Blood Flow Velocity↗