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N Arkadopoulos

Publications and source records attributed to N Arkadopoulos.

32 records · Page 2Linked to original sources
PubMed1998

Long chain versus medium chain lipids in patients with ARDS: effects on pulmonary haemodynamics and gas exchange.

OBJECTIVE: To compare pulmonary haemodynamic and gas exchange alterations in septic patients with ARDS receiving long-chain triglycerides (LCT) versus medium-chain triglycerides (MCT). DESIGN: Prospective, randomised, clinical study. SETTING: Surgical ICU patients in a University Hospital. PATIENTS: Twenty-one septic patients with ARDS were randomly assigned to receive 50 % of their non-protein caloric requirements as either 20 % LCT (group 1, n = 10) or 20% 1:1 mixture of LCT/MCT (group 2, n = 11). INTERVENTION: Intravenous infusion of LCT and LCT/MCT combinations at a rate of 12 g x h(-1). MEASUREMENTS AND RESULTS: The LCT infusion was associated with an increase of pulmonary venous admixture (Qva/Qt) from 24 % +/- 5 % to 37 % +/- 6 %, an increase of mean pulmonary artery pressure (MPAP) from 25 +/- 5 to 33 +/- 4 mmHg and decrease of PaO2/FIO2 from 240 +/- 30 to 180 +/- 35. LCT/MCT administration was only associated with an elevation of oxygen consumption (VO2) from 329 +/- 14 to 396 +/- 12 ml/ min. During lipid infusion group 1 patients presented higher Qva/Qt (37% +/- 6% vs 25% +/- 4%), MPAP (33 +/- 4 vs 27 +/- 3 mmHg) and VO2 (359 +/- 11 vs 396 +/- 12 ml/min) and lower PaO2/FIO2 (180 +/- 35 vs 235 +/- 30) values compared to group 2. CONCLUSION: In conclusion, we have shown that, in septic patients with respiratory failure, LCT administration was associated with more significant changes of Qva/Qt, MPAP and PaO2/FIO2 compared to infusion of an LCT/MCT 1:1 emulsion. Clinically, these transient alterations might cause serious problems in patients with marginal arterial oxygenation and cardio-respiratory impairment.

Adult↗
PubMed1998

Liver assist systems: state of the art.

Attempts to develop liver support systems for the treatment of patients with liver failure have ranged from use of plasma exchange to utilization of charcoal columns and extracorporeal devices loaded with liver tissue. However, no system has achieved wide clinical use and - in the absence of liver transplantation - severe hepatic failure continues to be associated with significant morbidity and mortality. In this paper, the authors review the current status of liver assist systems and summarize their clinical experience with a xenogeneic cell based-bioartificial liver.

Animals↗
PubMed1997

Treatment of severe liver failure with a bioartificial liver.

Orthotopic liver transplantation (OLT) is the definitive therapy for severe liver failure. However, many patients die before an organ becomes available, mostly from cerebral edema. To provide temporary liver support, we developed a bioartificial liver (BAL) based on porcine hepatocytes and a charcoal column. Fifty-four consecutive BAL treatments were carried out in three groups of patients: Group I (n = 15) patients presented with FHF were listed for emergent OLT, Group II (n = 3) patients with primary non-function (PNF) of their liver grafts required urgent re-transplantation and Group III (n = 10) patients with acute exacerbation of chronic liver disease were not candidates for OLT. Patients were managed in a critical care unit receiving maximal standard support. Each BAL treatment was conducted for 6 hours. In Group I, all patients showed significant neurologic improvement, intracranial pressure (ICP) decreased and cerebral perfusion pressure (CPP) increased; other significant improvements, included lowered plasma ammonia and liver enzymes and increased glucose. One patient recovered spontaneously without OLT, all other patients were "bridged" to OLT, and recovered. Group II: PNF patients showed similar benefits. Group III: Chronic liver patients demonstrated transient beneficial effects after BAL treatment(s), however, most (n = 8) eventually succumbed to sepsis and multiple organ failure as they were not candidates for OLT; two patients, recovered, later were successfully transplanted and survived. Our clinical experience demonstrates that the BAL can serve as a bridge to OLT in patients with acute liver failure.

Adult↗
PubMed1997

Fetal rat hepatocytes: isolation, characterization, and transplantation in the Nagase analbuminemic rats.

BACKGROUND: In contrast to adult hepatocytes, fetal hepatocytes (FH) are thought to be highly proliferative, less immunogenic, and resistant to cryopreservation and ischemic injury. These qualities could enhance FH engraftment, proliferation, and gene transfer requiring active DNA synthesis. METHODS: Rat FH were obtained using the nonperfusion collagenase/DNase digestion method. Free and cultured cells were studied using electron microscopy, fluorescence-activated cell sorting, and Northern analysis using alpha-fetoprotein and albumin as markers of hepatocyte lineage. DNA synthetic activity was measured in quiescent and mitogen-stimulated fetal and adult hepatocytes by [3H]thymidine incorporation. Susceptibility of cultured FH to retrovirally mediated gene transfer was studied using an amphotropic retroviral vector carrying the Escherichia coli lac-Z gene. Nagase analbuminemic rats were used as recipients to study the effects of intraportal FH transplantation. Analysis of serum albumin was carried out by enzyme-linked immunosorbent assay. RESULTS: In fetal liver, 87+/-2% of the cells showed morphological and molecular features of hepatocytes. DNA synthetic activity in nonstimulated cultured FH was 10 times greater than the maximal hepatocyte growth factor-driven response in adult rat hepatocytes. A total of 5-15% FH stained positive for X-gal; results of transduction in adult hepatocyte cultures were negative. In Nagase analbuminemic rat recipients, FH produced significant amounts of albumin only when a hepatic regenerative stimulus was applied. Immunohistochemistry confirmed presence of albumin-positive hepatocytes. CONCLUSIONS: Fetal rat liver from the late gestation period is highly enriched with hepatocyte progenitors. They are highly proliferative and susceptible to retroviral transduction and can engraft and function in the adult rat liver if transplanted under a hepatic regenerative stimulus.

Acetylglucosaminidase↗
PubMed1997

Lack of hepatocyte growth factor receptor (c-met) gene expression in fulminant hepatic failure livers before transplantation.

To gain insight into liver regeneration mechanisms in fulminant hepatic failure, we compared gene expression of hepatocyte growth factor, its receptor c-met, c-myc, and albumin in human normal (4 cases) and fulminant (14 cases) livers by reverse transcription-polymerase chain reaction. In normal livers, hepatocyte growth factor gene was not expressed, whereas c-met, c-myc and albumin genes were always expressed. In fulminant hepatic failure, hepatocyte growth factor gene was expressed in 1 of 14 cases, c-met in none of 14 cases, c-myc in 10 of 14 cases, and albumin in 3 of 14 cases. By immunofluorescence, c-met protein was revealed in normal but not in fulminant hepatic failure liver tissue. Liver tissue is unlikely to account for high hepatocyte growth factor plasma levels typical for fulminant hepatic failure. Lack of its receptor (c-met) expression may explain a poor response of fulminant hepatic failure livers to exogenous hepatocyte growth factor that normally promotes liver growth and regeneration.

Actins↗
PubMed1997

Clinical experience with a bioartificial liver in the treatment of severe liver failure. A phase I clinical trial.

OBJECTIVE: The purpose of this study was to develop a bioartificial liver (BAL) to treat patients with severe liver failure until they can be either transplanted or recover spontaneously. SUMMARY BACKGROUND DATA: Severe acute liver failure is associated with high mortality. Liver transplantation has emerged as an effective therapy for patients who did not respond to standard management. However, because of the donor organ shortage and urgent need for transplantation, many patients die before they can be transplanted and others do not survive after transplantation, primarily because of intracranial hypertension. METHODS: Three groups of patients with severe acute liver failure were treated with the BAL. In group 1 (n = 18) were patients with fulminant hepatic failure (FHF), in group 2 (n = 3) were patients with primary nonfunction (PNF) of a transplanted liver, and in group 3 (n = 10) were patients with acute exacerbation of chronic liver disease. Patients in groups 1 and 2 were candidates for transplantation at the time they entered the study, whereas patients in group 3 were not. RESULTS: In group 1, 16 patients were "bridged" successfully to transplantation, 1 patient was bridged to recovery without a transplant, and 1 patient died because of concomitant severe pancreatitis. In group 2, all patients were bridged successfully to retransplantation. In group 3, two patients were supported to recovery and successful transplants at later dates; the other eight patients, although supported temporarily with the BAL, later died because they were not candidates for transplantation. CONCLUSIONS: The authors' clinical experience with the BAL has yielded encouraging results. A randomized, controlled, prospective trial (phase II-III) is being initiated to determine the efficacy of the system.

Adult↗
PubMed1996

Abdominal aortic aneurysm combined with a second intraabdominal non vascular disease--a clinical study and surgical treatment.

The surgical tactics in cases of aneurysm of the infrarenal abdominal aorta and a second intraperitoneal operative procedure are not uniform in the literature and still remain a matter of debate. In 170 aneurysms of the abdominal aorta there were 18/170 (10.5%) other co-existent surgical non-vascular diseases as follows: Thirteen cases with symptomatic or asymptomatic cholecystopathy, one case with abdominal hernia, three cases with Ca of the colon and one case with Ca of the liver. In 9 cases, the aneurysm and the gallbladder were removed concomitantly, in 3 cases only aneurysmectomy was carried out due to cardiopulmonary problems, of which in two cholecystectomy was carried out in a second stage. In one case with cholecystitis, the gallbladder was removed and aneurysmectomy followed one month after. Aneurysmectomy and sigmoidectomy were carried out in one case and in a second similar case sigmoidectomy preceded followed by aneurysmectomy 6 months later. In one case aneurysmectomy and restoration of the abdominal hernia was performed concomitantly, while two more cases, one with liver lobectomy and another with orthosigmoidectomy due to Ca. No one of the above patients presented with any infection of the graft or other postoperative complication. No other complications were noted during a follow-up period of 19 months. The one stage operation management of infrarenal abdominal aortic aneurysm and a second (intra-abdominal) surgical procedure is feasible if appropriate care is given to the technical details and due consideration to the rules of antisepsis, without affecting surgical morbidity and mortality of the patient.

Aged↗
PubMed1994

Experimental transplantation of hepatocytes in cases of toxic acute liver failure. An allograft model.

The aim of this experimental study was to modify a rat liver-cell harvesting technique and to evaluate the efficacy of allogeneic liver cell transplantation (Tx) using cyclosporin A immunosuppression in rats with N-dimethylonitrosamine (N-DMNA)-induced acute liver failure (ALF). Twenty male Wistar rats, weighing 190-320 g, were used as donors. Hepatocytes were harvested by the use of a modification of the Seglen portal vein collagenase perfusion technique (type V/1.3 mg/ml), which resulted in the isolation of a mean of 8000 viable clusters of hepatocytes per donor (viability was measured using the trypan blue exclusion test). The male Lewis recipients and controls received 20 mg/kg N-DMNA i.v., and were then divided in three groups. Group 1 (n = 5) received no treatment, group 2 (n = 10) received 5000 clusters of freshly isolated hepatocytes (FIH) in the spleen 24 h after the administration of N-DMNA- and group 3 (n = 10) received 5000 clusters of FIH beneath the renal capsule, 24 h after the administration of N-DMNA. All groups were treated with cyclosporin A 20 mg/kg per day i.p.. SGOT and bilirubin values were measured and all surviving rats were sacrificed on day 14. All rats in group 1 died of histologically confirmed liver necrosis within 72 h. The 14-day survival was 60% in group 2 and 50% in group 3. The post-Tx SGOT values reached their maximum on days 3-4 (group 2, mean 754; group 3, mean 529) and were only slightly elevated on day 14 (group 2 = 75, group 3 = 48). The post-Tx bilirubin values reached their maximum on days 3-5 (group 2 = 1.1, group 3 = 1) but failed to return to normal until day 14. Autopsy and histological examination of the surviving animals showed well-preserved hepatocellular spherical aggregates in the spleen and hepatocellular "cords" in the kidney accompanied by signs of regeneration of the native liver. We concluded that the hepatocyte Tx in a rat experimental allo-Tx model improved the survival rate and the SGOT values in cases of toxic ALF. Survival rates between the two different sites of Tx were similar.

Animals↗
PubMed1994

Combined hepatocyte-islet transplantation: an allograft model.

Experimental hepatocyte transplantation (Tx) has been shown to improve the survival rate of acute hepatic failure (AHF) in different models. Histological and biochemical data from some studies suggest more satisfactory function of hepatocytes after combined hepatocyte-islet Tx. The aim of the present study was to compare the survival rate between two different sites of Tx (kidney subcapsular and spleen) of hepatocytes alone or combined with islets of Langerhans in rats with surgically induced AHF (90% hepatectomy) accross a major histocompatibility barrier (WAG to Lewis). Rats were divided into five groups (n = 6 in each group). Group 1 consisted of AHF without treatment, group 2, AHF followed by hepatocyte Tx into the spleen, group 3, AHF followed by hepatocyte Tx subcapsular into the kidney, group 4, AHF followed by combined hepatocyte islet Tx into the spleen, and group 5, AHF followed by combined hepatocyte islet Tx subcapsular into the kidney. The number of hepatocytes was 10(7) and the number of islets was 400. All rats received cyclosporin A (CsA) i.v. (20 mg/kg on days 0-4 and 10 mg/kg on days 5-30). Hepatocytes were harvested using a modification of the portal vein collagenase perfusion (type V 1.3 mg/ml) and islets, with the collagenase digestive technique (type XI 1 mg/ml). All Tx took place 24 h after AHF. All rats in group 1 died within 48 h. In groups 2 and 3, the combined survival rate was 33% 1 month after Tx, while in groups 4 and 5, the combined survival rate was 50% at 1 month. All surviving animals were sacrificed and histological examination showed well-preserved hepatocellular aggregates in the spleen and beneath the renal capsule, as well as islets around the clusters of hepatocytes. SGOT and SGPT values were also measured. We concluded that the combined Tx in a rat experimental allo-Tx model in cases of AHF improves the survival rate in comparison with hepatocyte Tx alone. The survival rate at the two different sites for combined Tx was similar.

Animals↗
PubMedDate not supplied

Hepatocyte function during experimental use of a bioartificial liver.

The aim of the present study was to compare the function of fresh versus cryopreserved hepatocytes in an experimental bioartificial liver system (BAL), especially designed to reproduce clinical parameters. Our BAL consists of a pump, a plasma reservoir, a membrane oxygenator, and a hollow fiber module loaded with 5 x 10(9) isolated porcine hepatocytes, either fresh (n = 5) or cryopreserved (n = 5). In the present setting, the system was isolated and perfused for 6 hours with recirculating plasma obtained from pigs with ischemic liver failure (toxic plasma). The following parameters were studied at 0 and 6 hours: oxygen consumption by the hepatocytes in the bioreactor, hepatocyte viability, as well as plasma concentrations of AST, LDH, ammonia, urea, and total bilirubin. MEGX concentrations were measured following injection of lidocaine into the system 30 minutes after initiation of plasma recirculation. Compared to cryopreserved cells, fresh hepatocytes showed higher viability at both time points studied (P <.05). Furthermore, during BAL sessions, ammonia levels were reduced while urea, AST, and LDH levels were increased with both preservation types (P <.05). Total bilirubin levels increased only during sessions with cryopreserved hepatocytes. After lidocaine administration, both fresh and cryopreserved hepatocytes were capable of producing MEGX; however, fresh-cell bioreactors produced significantly more MEGX at both 30 and 60 minutes after lidocaine administration. Oxygen consumption was significantly higher by fresh-cell bioreactors both before and after BAL use. In conclusion, hepatocytes in the BAL bioreactor showed preservation of important metabolic functions, when perfused with homologous toxic plasma. Fresh cells appeared to respond better than did cryopreserved ones.

Animals↗
PubMedDate not supplied

Transplantation of hepatocytes for prevention of intracranial hypertension in pigs with ischemic liver failure.

Intracranial hypertension leading to brain stem herniation is a major cause of death in fulminant hepatic failure (FHF). Mannitol, barbiturates, and hyperventilation have been used to treat brain swelling, but most patients are either refractory to medical management or cannot be treated because of concurrent medical problems or side effects. In this study, we examined whether allogeneic hepatocellular transplantation may prevent development of intracranial hypertension in pigs with experimentally induced liver failure. Of the two preparations tested--total hepatectomy (n = 47), and liver devascularization (n = 16)--only pigs with liver ischemia developed brain edema provided, however, that animals were maintained normothermic throughout the postoperative period. This model was then used in transplantation studies, in which six pigs received intrasplenic injection of allogeneic hepatocytes (2.5 x 10(9) cells/pig) and 3 days later acute liver failure was induced. In both models (anhepatic state, liver devascularization), pigs allowed to become hypothermic had significantly longer survival compared to those maintained normothermic. Normothermic pigs with liver ischemia had, at all time points studied, ICP greater than 20 mmHg. Pigs that received hepatocellular transplants had ICP below 15 mmHg until death; at the same time, cerebral perfusion pressure (CPP) in transplanted pigs was consistently higher than in controls (45 +/- 11 mmHg vs. 16 +/- 18 mmHg; p < 0.05). Spleens of transplanted pigs contained clusters of viable hepatocytes (hematoxylin-eosin, CAM 5.2). It was concluded that removal of the liver does not result in intracranial hypertension; hypothermia prolongs survival time in both anhepatic pigs and pigs with liver devascularization, and intrasplenic transplantation of allogeneic hepatocytes prevents development of intracranial hypertension in pigs with acute ischemic liver failure.

Animals↗