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At least 109 records · Page 6Linked to original sources

PubMed2002

In vitro removal of therapeutic drugs with a novel adsorbent system.

BACKGROUND/AIMS: Substances in the middle molecular weight range have been shown to play a significant pathogenetic role in as diverse disorders as end-stage renal disease and multiple organ failure. To overcome the limitations in the amount removed by hemofilters, new sorbents with a high biocompatibility are actively being developed. Furthermore, biocompatible sorbents by their nonspecific adsorptive behavior could have great impact on detoxification treatment in exogenous intoxications. We performed an in vitro evaluation of a newly developed highly biocompatible sorbent cartridge (Betasorb((R))), examining its adsorptive capacity concerning therapeutic drugs. METHODS: Uremic blood spiked with a range of therapeutic drugs was recirculated for 2 h in an in vitro hemoperfusion circuit containing a Betasorb device for hemoperfusion. The drug concentrations before and after the passage of the cartridge were measured, and the total amount removed was calculated. RESULTS: The sorbent showed effective removal of glycopeptide antibiotics, digoxin, theophylline, phenobarbital, phenytoin, carbamazepine, and valproic acid. Moderate removal could be demonstrated for tacrolimus and cyclosporine A; aminoglycosides were removed to a small extent only. CONCLUSION: Betasorb hemoperfusion shows a potent adsorptive capacity concerning therapeutic drugs (except aminoglycosides) and could be of major value in the treatment of intoxications. On the other hand, drug monitoring and possible adjustments are necessary during Betasorb hemoperfusion to maintain the therapeutic ranges of the drugs in blood.

Adsorption↗

PubMedDate not supplied

[MARS (Molecular Adsorbents Recirculating System). New technique of extracorporeal depuration in liver failure].

MARS (Molecular Adsorbent Recirculating System) is a new technique as a system of liver detoxification in patients with severe acute or acute on chronic hepatic failure. Also, it has shown its usefulness in the control of resistant pruritus in the primary biliary cirrhosis. Due to the fact that this technique is often delivered in Intensive Care Units (ICUs), we have reviewed the literature 1999 until now to describe this technique, its benefits and its mains complications. The technique was developed in Germany, where in 1999 was first used in clinical practice. It was used for the first time in Spain in 2000 and in the Clínica Universitaria of Navarra in July of 2001. Despite the short clinical experience using MARS its obvious beneficial effects such as decrease of hepatic toxins and the improvement of encephalopathy and hemodynamic situation, makes it a very useful technique in these patients. MARS has been shown to be a safe procedure, well tolerated by patients and accessible to the use by specialised nurses. Despite the encouraging clinical results, its used is still limited. Moreover its high cost precludes it widespread use and requires further studies.

Clinical Trials as Topic↗

PubMed2002

The molecular adsorbents recycling system as a liver support system based on albumin dialysis: a summary of preclinical investigations, prospective, randomized, controlled clinical trial, and clinical experience from 19 centers.

Artificial liver support aims to prolong survival time of patients with liver failure by detoxification. Albumin as a molecular adsorbent in dialysis solution is capable of attracting even tightly albumin-bound toxins from blood into the dialysate if a specific dialysis membrane is used and if the albumin's binding sites are on-line-purified by a sorbent/dialysis-based recycling system (i.e., molecular adsorbents recycling system, or MARS). The MARS technology has been shown to remove water-soluble and albumin-bound toxins and to provide renal support in case of renal failure. Fourteen centers have reported that MARS treatment improved mental status of patients with liver failure and hepatic encephalopathy. In treating liver failure and cholestasis, MARS was associated with hemodynamic stabilization, improvement of hepatic and kidney function, and disappearance of pruritus. In hepatic failure and hepatorenal syndrome, a prospective, randomized, controlled trial of MARS treatment was able to prolong survival time significantly. MARS has been used in 26 patients with acute liver failure or primary graft dysfunction. Nineteen centers reporting on 103 patients have shown that MARS treatment is safe, easy to handle, feasible, and effective.

Adsorption↗

PubMed1999

Dietary clay in the chemoprevention of aflatoxin-induced disease.

Aflatoxins are harmful by-products of mold growth and, though invisible to the naked eye, are potentially fatal. The aflatoxin problem is long-standing and inextricable. Concerns about the aflatoxins originate from the strong implications of their involvement in disease and death in humans and animals, yet scientists and clinicians are still seeking ways to effectively deal with these dangerous and elusive chemicals. Safe, practical, and effective strategies for the detoxification of aflatoxin-contaminated food and feed are highly desirable. A simple and effective approach to the chemoprevention of aflatoxicosis has been to diminish or block exposure to aflatoxins via the inclusion of HSCAS clay in the diet. HSCAS clay acts as an aflatoxin enterosorbent that tightly and selectively binds these poisons in the gastrointestinal tract of animals, decreasing their bioavailability and associated toxicities. Further studies to delineate the molecular mechanisms of action have shown that the dicarbonyl system of aflatoxin is essential for tight binding by HSCAS. In these studies, adsorption data was fitted to multiple isotherm equations including the Langmuir, multi-Langmuir, general Freundlich, Langmuir-Freundlich, Toth and various transforms. Information derived included: the Gibbs standard free energy change of adsorption, enthalpy of adsorption, capacity, affinity, and heterogeneity coefficient. Computer modeling was also utilized to provide additional structural information and insight into the mechanism. Evidence suggests that aflatoxins may react at multiple sites on HSCAS particles, especially the interlayer region, but also at edges and basal surfaces. Since clay and zeolitic minerals comprise a broad family of functionally diverse chemicals, there may be significant hidden risks associated with their indiscriminate inclusion in the diet. All aflatoxin binding agents should be rigorously tested, paying particular attention to their effectiveness and safety in aflatoxin-sensitive animals and their potential for interactions with critical nutrients.

Aflatoxins↗

PubMed2003

Prometheus--a new extracorporeal system for the treatment of liver failure.

BACKGROUND/AIMS: Extracorporeal detoxification systems for supportive therapy of liver failure have recently gained much interest. We herein report results from the first clinical application of Prometheus, a new liver support system in which albumin-bound substances are directly removed from blood by special adsorber. In a simultaneous step, high-flux hemodialysis is performed. We assessed safety, adsorber efficiency and clinical efficacy of the Prometheus system. METHODS: Eleven patients with acute-on-chronic liver failure and accompanying renal failure were treated with Prometheus on 2 consecutive days for >4 h. RESULTS: Prometheus treatment significantly improved serum levels of conjugated bilirubin, bile acids, ammonia, cholinesterase, creatinine, urea and blood pH. There were no significant changes in hemoglobin and platelet levels, whereas leucocytes increased without signs of systemic infection. No treatment-related complications except a blood pressure drop in two patients with systemic infection were noted. In one patient (Child-Pugh score: 15) Prometheus treatment could not be completed due to onset of uncontrolled bleeding 16 h after dialysis. CONCLUSIONS: Prometheus is a safe supportive therapy for patients with liver failure. A significant improvement of the biochemical milieu was observed already after two treatments. Prospective controlled studies with the Prometheus system are necessary to evaluate hard clinical end-points.

Adult↗

PubMed2001

Detoxification of endotoxin by aluminum hydroxide adjuvant.

Langmuir adsorption isotherms of endotoxin and aluminum-containing adjuvants at pH 7.4 and 25 degrees C revealed that aluminum hydroxide adjuvant has a greater adsorption capacity (283 microg/mg Al) and adsorption coefficient (1.3x10(4) ml/miccrog) than aluminum phosphate adjuvant (3.0 microg/mg Al, 0.20 ml/microg). The difference in endotoxin adsorption was related to two adsorption mechanisms: electrostatic attraction and covalent bonding. The isoelectric point (iep) of endotoxin is approximately 2. An electrostatic attractive force will be present with aluminum hydroxide adjuvant (iep=11.4), and an electrostatic repulsive force will operate with aluminum phosphate adjuvant (iep=4.6). Endotoxin contains two phosphate groups in the lipid A portion. Covalent bonding occurs with surface aluminum in aluminum hydroxide adjuvant but is inhibited by surface phosphate in aluminum phosphate adjuvant. In-vitro desorption experiments using components of interstitial fluid showed that endotoxin adsorbed by aluminum hydroxide adjuvant was not desorbed by interstitial anions (5 mM phosphate or 2.7 mM citrate) or interstitial proteins (25 mg albumin/ml). The effect of aluminum-containing adjuvants on the systemic response of Sprague-Dawley rats to a 15 microg/kg subcutaneous dose of endotoxin was determined by measuring the serum concentration of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). TNF-alpha and IL-6 were observed in the group which received an endotoxin solution or endotoxin and aluminum phosphate adjuvant. No TNF-alpha or IL-6 was detected in the group that received endotoxin and aluminum hydroxide adjuvant. Aluminum hydroxide adjuvant detoxifies endotoxin by adsorbing it in the vaccine and then not releasing it in interstitial fluid upon administration.

Adjuvants, Immunologic↗

PubMed2001

Extracorporeal detoxification using the molecular adsorbent recirculating system for critically ill patients with liver failure.

Liver failure resulting from different causes and its concomitant complications represent difficult-to-treat conditions with high mortality rates, despite improved therapeutic modalities in intensive care medicine. The accumulation of albumin-bound metabolites that are normally cleared by the liver, such as bilirubin and bile acids, contributes substantially to the development of multiorgan dysfunction in these clinical situations. The molecular adsorbent recirculating system (MARS) represents a cell-free, extracorporeal, liver assistance method for the selective removal of albumin-bound substances. Moreover, it enables the removal of excess water and water-soluble substances via an inbuilt dialysis step. Since 1993, >400 patients have been treated in 53 centers in Europe, the United States, and Asia. Diseases treated with MARS included acute exacerbation of chronic hepatic failure, hepatorenal syndrome, acute hepatic failure, and primary nonfunction/poor function after liver transplantation and major liver resection. Treatments were well tolerated. No severe adverse events were observed. Six- to 8-h MARS treatments resulted in significant (P < 0.05) removal of bilirubin, bile acids, tryptophan, short- and middle-chain fatty acids, aromatic amino acids, and ammonia. Clearance rates for strongly albumin-bound substances were between 10 and 60 ml/min. The removal of albumin-bound toxins resulted in decreases in hepatic encephalopathy, increases in mean arterial pressure, and improvements in kidney and liver function. In the first randomized clinical trial of the MARS method for treatment of the hepatorenal syndrome, significant prolongation of survival was observed for the MARS-treated group. It is concluded that the MARS method can contribute to the treatment of critically ill patients with liver failure and different underlying diseases.

Critical Illness↗

PubMed2006

Prometheus versus molecular adsorbents recirculating system: comparison of efficiency in two different liver detoxification devices.

Albumin dialysis by the molecular adsorbents recirculating system (MARS) and by fractionated plasma separation, adsorption, and dialysis (Prometheus[PROM]) represent novel nonbiological liver support systems specifically designed to remove albumin-bound substances. Preliminary evidence suggests a favorable impact of MARS on the course and outcome of liver failure. This study aimed at comparing the detoxification capacity of both devices. For this purpose, we performed a retrospective analysis on data prospectively collected in patients with acute-on-chronic liver failure treated with either the MARS (n = 9) or the PROM (n = 9) device on 2-5 consecutive days. Each treatment was performed for at least 5 h at identical blood and dialysate flows. Blood clearances were calculated during the first treatment session for urea nitrogen, creatinine, total bilirubin, and bile acids from paired arterial and venous line samples after 1, 4, and 6 h of treatment. Reduction ratios for all single-treatment sessions, and the overall treatment phase, were calculated from pretreatment and post-treatment values. For all markers but bile acids, the single-treatment as well as the overall treatment phase reduction ratios obtained with PROM were significantly higher compared with those obtained with MARS. PROM led at all time points to higher clearances for all evaluated solutes. Blood clearances of protein-bound substances declined over time with MARS, but not with PROM. In conclusion, a significant decline in the serum level of water-soluble and protein-bound toxins was achieved with both devices. PROM produces higher blood clearances for most toxins, which results in higher delivered treatment doses compared with a matching treatment with MARS.

Adult↗

PubMed2002

Treatment of severe tricyclic antidepressant overdose with extracorporeal sorbent detoxification.

Tricyclic overdose can be a medical emergency, and therapy with intravenous bicarbonate is not always successful in preventing cardiac toxicity or coma. Mortality in patients developing these complications is from 1% to 15%. Extracorporeal detoxification with sorbents has been used in treatment of patients with very high drug levels and declining clinical condition. Ten patients with serious drug overdose caused by tricyclics failed to respond quickly to standard therapy and were in stage 3-4 encephalopathy. Nine of these patients were on respirator support, 5 had hypotension, and 6 had QRS widening. Average level was 1,423 microg/L at presentation. Enteral activated charcoal and intravenous (IV) bicarbonate were initiated in the emergency room. The patients were treated for 3 to 4 hours with the Liver Dialysis Unit, a hemodiabsorption device using a cellulosic plate dialyzer and sorbent suspension as dialysate. Inflow and outflow blood levels indicated that the hemodetoxifier removed modest amounts of the tricyclics, metabolites, and other consumed drugs. The clinical improvement of the patients was dramatic, with patients reaching stage 0 or 1 encephalopathy during the treatment. Ventilator support was removed at the end of treatment for 3 patients who had not already developed pneumonia, and for others was prolonged up to 48 hours because of pneumonia, rather than mental status. Average length of stay in the intensive care unit (ICU) was 4.8 days (range 1 to 7 days). None of the patients died despite their high risk for ventricular arrhythmias, seizures, and death. Clinical improvement may have been attributable to removal of free drug from the blood or to removal of drug metabolites.

Antidepressive Agents, Tricyclic↗

PubMed2000

Biocompatibility of a cuprophane charcoal-based detoxification device in cirrhotic patients with hepatic encephalopathy.

Extracorporeal detoxification has been proposed to treat patients with hepatic encephalopathy (HE) not responding to standard therapy. To investigate the biocompatibility of a cuprophane charcoal-based detoxification device, a prospective, randomized, controlled study was performed. Of 41 consecutive patients with cirrhosis and HE grade II or III who did not improve with conventional treatment, 20 patients (median age, 56 years; range, 33 to 71 years; 13 men) were randomly assigned to either ongoing conventional treatment or one additional 6-hour treatment with a sorbent suspension dialysis system. Main outcome parameters were physiological function and blood parameters of biocompatibility. In the 10 patients undergoing combined conventional and sorbent suspension dialysis treatment, blood pressure remained unchanged and body temperature and heart rate increased (P: < 0.01). Platelet count decreased (medians, from 75 to 26 g/L; P: < 0.001) and international normalized ratio increased after combined treatment (2.0 to 2.2; P: < 0.001). Three patients developed bleeding complications during treatment or shortly after. Treated patients showed increases in levels of plasma elastase (104 to 586 microg/L; P: = 0.001), tumor necrosis factor-alpha (5.4 to 7.5 pg/mL; P: = 0.04), and interleukin-6 (118 to 139 pg/mL; P: = 0.04), but not interferon-gamma and E-selectin. No changes were observed in the 10 patients treated conventionally. In conclusion, despite technical refinements compared with charcoal hemoperfusion, biocompatibility of sorbent suspension dialysis is still very limited. Clinical complications were apparently caused by blood-membrane interactions and disseminated intravascular coagulation. We suggest further developments in design and appropriate strategies of anticoagulation to improve the biocompatibility of artificial liver support.

Adult↗

PubMed2002

Amino acid dysbalance in liver failure is favourably influenced by recirculating albumin dialysis (MARS).

INTRODUCTION: Dysbalance between branched chain (BCAA) and aromatic amino acids (AAA), which can be quantified by a low Fischer's Index (SigmaBCAA/SigmaAAA), as well as elevated levels of free tryptophan in plasma are common in hepatic failure and may contribute to the development of hepatic encephalopathy. AIM: To evaluate the influence of a new extracorporeal detoxification system for liver failure (Molecular Adsorbents Recirculating System, MARS(R), i.e. dialysis against a recirculating albumin solution cleaned online by charcoal and an anion exchange resin) on plasma tryptophan and Fischer's Index. METHODS: Plasma samples were taken before, during and after MARS treatments (n = 11, mean blood flow 135 ml/min, mean dialysate flow 120 ml/min, high flux polysulfone membrane). Simultaneous to blood sampling, aliquots of the albumin dialysate were taken between the elements of the dialysate circuit. RESULTS: Fischer's Index in systemic blood increased during MARS by 24% (from 1.44 to 1.79, P < 0.001; mean treatment duration, 5.5 h). Systemic tryptophan level was significantly reduced at the same time (-25%, n = 8). Amino acid removal rates from plasma during a single dialyser passage ranged from 10 to 53%. In particular, AAA were preferentially removed (42-44% throughout treatment), while BCAA removal was 28-46% initially and later declined to 24-28%. A maximum concentration gradient between plasma and dialysate was maintained for the AAA throughout treatment through their apparently complete removal by the charcoal adsorber. Conversely, BCAA removal at both adsorbers was only minor. As a result, Fischer's Index showed a significant increase in the processed plasma, which became even more pronounced with increasing treatment duration. CONCLUSIONS: MARS enables an elevation of a pathologically decreased Fischer's Index as well as a reduction of systemic tryptophan levels in patients with liver failure. The effects of MARS on plasma amino acid dysbalance may contribute to an improvement of hepatic encephalopathy.

Amino Acids↗

PubMed2002

Treatment of acetaminophen-induced hepatitis and fulminant hepatic failure with extracorporeal sorbent-based devices.

When a patient with acetaminophen overdose arrives in the emergency room more than 14 hours after ingestion, the value of N-acetylcysteine is unproven and patient mortality is at least 10%. Anecdotal case reports have indicated benefit of extracorporeal detoxification of these late-arriving patients with acetaminophen overdose. We identified 10 patients with serious acetaminophen overdose, 8 that arrived in the emergency room 16 to 44 hours after acetaminophen overdose with plasma levels predicting severe hepatic toxicity, and 2 that arrived in the emergency room 8 to 12 hours after overdose but with exceedingly high levels. All patients developed severe hepatitis (mean peak alanine aminotransferase, 4,052; mean peak protime, 25 seconds). At 16 to 68 hours after overdose, the patients were treated for 4 to 6 hours with the Liver Dialysis System (Hemocleanse Inc, W. Lafayette, IN), a single-access hemodiabsorption system indicated for treatment of serious drug overdose and for treatment of hepatic encephalopathy. Acetaminophen levels fell an average of 73% during treatment. Treatment was repeated 24 or 48 hours later if acetaminophen was still measurable in plasma. All 10 patients recovered intrinsic liver function and general health, with liver enzymes starting to normalize 24 hours after treatment, and were discharged 3 to 7 days after overdose. No patient required liver transplant. Because market introduction of Liver Dialysis, there have been 40 more patients with acetaminophen-induced hepatotoxicity treated with Liver Dialysis. All have recovered liver function without long-term sequelae. Though most of these patients with already established hepatic toxicity from acetaminophen would recover without extracorporeal blood therapy, treatment with the Liver Dialysis System should assure recovery from acute hepatic failure, and may shorten the clinical course of the illness.

Acetaminophen↗

PubMed2005

Removal of metabolites, cytokines and hepatic growth factors by extracorporeal liver support in children.

BACKGROUND: Molecular Adsorbents Recirculating System (MARS)-mini has recently been approved and applied in children with hepatic failure. However, its indication, efficacy and capability to induce liver regeneration remain unclear. The aim of our pilot study in children was to analyse the impact of MARS on markers of detoxification and regeneration. METHODS: In children with fulminant Wilson's disease and bridged with MARSmini for liver transplantation, we analyzed toxic metabolites (bile acids, bilirubin, lactate, ammonia, tryptophan and copper), regulators of the inflammatory cascade [nitrate, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), methionine, cystine and hyaluronic acid] and hepatic growth factors [hepatocyte growth factor (HGF), epidermal growth factor (EGF), transforming growth factor-beta1 (TGF-beta1), cortisol, corticosteroid-binding globulin (CBG), insulin-like growth factor-1 (IGF-1), angiogenin, vascular endothelial growth factor (VEGF), IL-6 and TNF-alpha] from blood, albumin circuit and haemodialysate from four applications. RESULTS: In all four applications, transfer of toxic metabolites (6/6) and inflammatory mediators (6/6), but also of hepatic growth factors (9/10), into the albumin circuit of MARS was consistently detected. Corresponding blood levels were decreased for 3/6 metabolites, 3/6 inflammatory mediators and 1/10 growth factors and increased for 1/10 growth factors. Bridging for liver transplantation was successful with MARS. CONCLUSIONS: In our prospective study, substantial extraction of albumin-bound and water-soluble candidate substances was detected with variable effect on respective blood levels. Notably, essential factors inducing liver regeneration were simultaneously removed. These data provide a basis for evaluation of liver restoration and efficacy of liver support in children with liver failure to devise a collaborative, multicentre trial.

Adolescent↗

PubMed2002

Extracorporeal blood detoxification by sorbents in treatment of hepatic encephalopathy.

Extracorporeal blood detoxification by sorbent therapy long has been applied in treatment of hepatic failure and encephalopathy, starting with hemoperfusion columns and more recently with the currently marketed Liver Dialysis Unit. Liver Dialysis employs hemodiabsorption (dialysis of blood against powdered sorbents including charcoal and cation exchanger) to remove selectively numerous small-molecular-weight toxins of hepatic failure. Liver Dialysis is used in treatment of acute hepatic encephalopathy (AHE) because of decompensation of chronic liver disease (A-on-C) or fulminant hepatic failure (FHF). Controlled, prospective and randomized studies of daily 6-hour Liver Dialysis have shown physiologic and neurologic improvement of patients with AHE, regardless of etiology. Liver dialysis significantly improved the incidence of positive outcomes (recovery of hepatic function or improvement for transplant) of A-on-C patients versus controls (71.5% treated, and 35.7% control, P =.036), but had an insignificant improvement in outcome of patients with FHF as compared with the control group. Other extracorporeal sorbent devices are now in clinical testing phase. The molecular adsorbent regenerating system (MARS) device employs a polysulfone high-permeability dialyzer with albumin on the dialysate side to aid transfer of protein-bound toxins such as bilirubin and bile acids across the membranes. Sorbent columns of charcoal and an anion exchanger remove hepatic toxins from the albumin dialysate, and a second dialyzer removes water-soluble toxins, such as ammonium. Clinical results of daily MARS treatments of patients with hepatic failure are similar to that of Liver Dialysis, with neurologic and physical improvement occurs in most patients with AHE, and improved outcome for patients with A-on-C. The system extends the life of patients with hepatorenal syndrome. PF-Liver Dialysis is an experimental device combining hemodiabsorption with push-pull sorbent-based pheresis with powdered sorbent surrounding plasmafilters. PF-Liver Dialysis (Hemocleanse, Inc, W. Lafayette, IN) has been tested in a few patients with hepatic failure, grade 3-4 encephalopathy, and respiratory and kidney insufficiency. Treatments appeared to be safe and resulted in marked decreases in plasma levels of bilirubin, aromatic amino acids, ammonium, creatinine, and interleukin-1beta (IL-1beta). The PF add-on module adds the capability to Liver Dialysis to remove bilirubin, bile acids, and other strongly protein-bound toxins from treated patients and may be of clinical benefit in management of patients with the most severe hepatic failure and encephalopathy, including patients with FHF or concomitant sepsis.

Hemodiafiltration↗

PubMed2004

Artificial liver support: potential to retard regeneration?

HYPOTHESIS: The concept of an "artificial liver" has been in development for over 40 years. Such devices aim to temporarily assume metabolic and excretory functions of the liver, with removal of potentially hepatotoxic substances, thereby clinically stabilizing patients and preventing deterioration while awaiting transplantation. If sufficient numbers of viable hepatocytes remain, regeneration and subsequent recovery of innate liver function may occur. However, these devices have not yet become part of routine clinical use. Much less is known regarding the effect such devices have, if any, on circulating cytokines and growth factors and the subsequent effects on the regenerating liver. If these devices remove or reduce factors known to promote regeneration, is the rate of regeneration retarded? Conversely, does the incorporation of hepatocytes into bioartificial support systems confer an advantage through the production of growth-promoting factors from these cultured hepatocytes?Data Sources, Extraction, and STUDY SELECTION: Data were obtained using PubMed search for reports involving liver support, extracorporeal circuits, dialysis, growth factors, and cytokines. Those reports specifically looking at the effect of artificial liver support on cytokines and growth factors are discussed. CONCLUSIONS: There is a paucity of information on the key events and substances involved in hepatic regeneration. In addition, there is a potential impact of liver support devices on the regeneration of substances associated with hepatic regeneration. Further study is needed.

Growth Substances↗

PubMed2003

Artificial and bioartificial support systems for acute and acute-on-chronic liver failure: a systematic review.

CONTEXT: Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation. OBJECTIVE: To evaluate the effect of artificial and bioartificial support systems for acute and acute-on-chronic liver failure. DATA SOURCES: Randomized trials on any support system vs standard medical therapy were included irrespective of publication status or language. Nonrandomized studies were included in explorative analyses. Trials were identified through electronic searches (Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Library, MEDLINE, EMBASE, and the Chinese Medical Database), bibliographies, and contact with experts. Searches were conducted of the entire databases through September 2002. STUDY SELECTION: Of 528 references identified, 12 randomized trials with 483 patients were included. Eight nonrandomized studies were included in explorative analyses. DATA EXTRACTION: Data were extracted and trial quality was assessed independently by 3 reviewers (L.L.K., J.L., B.A-N.). The primary outcome measure was all-cause mortality. Results were combined on the risk ratio (RR) scale. Random-effects models were used. Sources of heterogeneity were explored through meta-regression and stratified meta-analyses. DATA SYNTHESIS: Of the 12 trials included, 10 assessed artificial systems for acute or acute-on-chronic liver failure and 2 assessed bioartificial systems for acute liver failure. Overall, support systems had no significant effect on mortality compared with standard medical therapy (RR, 0.86; 95% confidence interval [CI], 0.65-1.12). Meta-regression indicated that the effect of support systems depended on the type of liver failure (P =.03). In stratified meta-analyses, support systems appeared to reduce mortality by 33% in acute-on-chronic liver failure (RR, 0.67; 95% CI, 0.51-0.90), but not in acute liver failure (RR, 0.95; 95% CI, 0.71-1.29). Compared with randomized trials, nonrandomized studies produced significantly larger estimates of intervention effects (P =.01). CONCLUSION: This review suggests that artificial support systems reduce mortality in acute-on-chronic liver failure compared with standard medical therapy. Artificial and bioartificial support systems did not appear to affect mortality in acute liver failure.

Chronic Disease↗

PubMed2004

Mechanisms of biosorption of different heavy metals by brown marine macroalgae.

The biosorption mechanisms of different heavy metallic cations (Cd, Ni, Pb) to active chemical groups on the cell wall matrix of the nonliving brown marine macroalga, Sargassum vulgaris in its natural form, were examined by the following instrumental and chemical techniques: Fourier-transform infrared (FTIR) analysis, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and extraction of alginic acid and sulfated polysaccharides, which act as metal-binding moieties present in cell wall. From the different techniques used and the known chemical composition of the algal cell wall, it was observed that biosorption of the metallic cations to the algal cell wall component was a surface process. The binding capacities of the different metal cations were between 1 and 1.2 mmol metal/g on a dry weight basis. The main chemical groups involved in the metallic cation biosorption were apparently carboxyl, amino, sulfhydryl, and sulfonate. These groups were part of the algal cell wall structural polymers, namely, polysaccharides (alginic acid, sulfated polysaccharides), proteins, and peptidoglycans. The main cadmium cation sequestration mechanism by the algal biomass was apparently chelation, while the nickel cation sequestration mechanism was mainly ion exchange. Lead cations exhibit higher affinity to the algal biomass, and their binding mechanism included a combination of ion exchange, chelation, and reduction reactions, accompanied by metallic lead precipitation on the cell wall matrix. During the ion exchange process, calcium, magnesium, hydrogen cations, and probably other cations (sodium and potassium) in the algal cell wall matrix were replaced by the tested heavy metals.

Absorption↗

PubMed1991

Experimental models of plasma perfusion.

A system allowing repeated plasma perfusion in the unrestrained conscious rat was developed in order to examine the effects of plasma filtration with on-line sorbent treatment of plasma in various models of disease. In experimental autoimmune glomerulonephritis, perfusion over a column coated with glomerular basement membrane (GBM) antigen lowered circulating levels of anti-GBM antibodies. In experimental endotoxaemia, perfusion over a column coated with polymixin B (PB) lowered circulating endotoxin levels and protected animals from haematological abnormalities and death. In experimental acute hepatic failure, perfusion over a combination of charcoal, resin, and PB columns improved survival in grades II and III hepatic coma. This experimental system has allowed preclinical evaluation of the effectiveness of different sorbents in the treatment of a range of disorders.

Animals↗