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Biomedical subjects

I M Sauer

Publications and source records attributed to I M Sauer.

17 recordsLinked to original sources
PubMed2005

[Clinical results of intestinal and multivisceral transplantation at the Charité, Berlin. A case series].

BACKGROUND AND OBJECTIVE: Intestinal transplantation (ITx) is the only causal therapy of short bowel syndrome (SBS). Long-term survival after ITx has been improved significantly during the last years. The experience with ITx at the Charite, Campus Virchow Klinikum, are described and discussed. PATIENTS AND METHODS: Twelve isolated ITx and one multivisceral transplantation (including stomach, pancreatodudenal complex, small intestine, liver, ascending colon, right kidney, and adrenal gland) were performed. Mean recipient age was 37.7+/-10.6 yrs (median: 35 yrs; range: 27 - 58 yrs; M:F = 8:5). All patients had irreversible SBS (0 - 30 cm residual bowel length; mean: 11.8+/-11.4 cm; median: 13 cm). RESULTS: 6-months and 1-year patient and graft survival were 85 % (11/13) and 77 % (10/13), respectively. Reasons for graft loss and patient death were necrotizing enterocolitis, severe, muromonab-resistent, acute rejection, and graft ischemia due to complex coagulopathy. All other patients had good long-term outcome. They received enteral nutrition at six hours after operation and were persistently off total parenteral nutrition (TPN) by week two after ITx. CONCLUSION: ITx as established in our centre, with 1-year-patient and graft survival rates of 77 %, reflects current international standard. ITx is complementary to conservative and other operative methods of treating SBS. Referral and indication criteria need wider dissemination to prevent life-threatening complications of TPN.

Adolescent↗
PubMed2005

Bioartificial liver: current status.

Liver failure remains a life-threatening syndrome. With the growing disparity between the number of suitable donor organs and the number of patients awaiting transplantation, efforts have been made to optimize the allocation of organs, to find alternatives to cadaveric liver transplantation, and to develop extracorporeal methods to support or replace the function of the failing organ. An extracorporeal liver support system has to provide the main functions of the liver: detoxification, synthesis, and regulation. The understanding that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver led to the development of artificial filtration and adsorption devices (artificial liver support). Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile acids, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be beneficial to the clinical course of a patient in liver failure. Artificial detoxification devices currently under clinical evaluation include the Molecular Adsorbent Recirculating System (MARS), Single-Pass Albumin Dialysis (SPAD), and the Prometheus system. The complex tasks of regulation and synthesis remain to be addressed by the use of liver cells (bioartificial liver support). The Extracorporeal Liver Assist Device (ELAD), HepatAssist, Modular Extracorporeal Liver Support system (MELS), and the Amsterdam Medical Center Bioartificial Liver (AMC-BAL) are bioartificial systems. This article gives a brief overview on these artificial and bioartificial devices and discusses remaining obstacles.

Humans↗
PubMed2003

Clinical extracorporeal hybrid liver support--phase I study with primary porcine liver cells.

The objective of this study was to evaluate the feasibility and safety of a hybrid liver support system with extracorporeal plasma separation and bioreactor perfusion in patients with acute liver failure (ALF) who had already fulfilled the criteria for high urgency liver transplantation (LTx). Eight patients (one male, seven female) were treated in terms of bridging to transplantation. The mean age was 36.5 yr (range 20 to 58). Etiology of liver failure was drug-related in two patients, hepatitis B infection in three patients, and unknown for three patients. The bioreactors were charged with primary liver cells from specific pathogen-free pigs. Cell viability varied between 91 and 98%. Continuous liver support treatment over a period of 8 to 46 h (mean 27.3 h) was safely performed and well-tolerated by all patients. No complications associated with the therapy were observed during the follow-up period. Thrombocytopenia was considered to be an effect of the plasma separation. Subsequently, all patients were transplanted successfully and were observed over at least 3 yr with an organ and patient survival rate of 100%. Screening of patient's sera for antibodies specific for porcine endogenous retroviruses (PERVs) showed no reactivity--either prior to application of the system, or after extracorporeal treatment. The results encourage us to continue the development of the technology, and further studies appear to be justified. The bioreactor technology has been integrated into a modular extracorporeal liver support (MELS) system, combining biologic liver support with artificial detoxification technology.

Adolescent↗
PubMed2002

[Living donor liver transplantation of the right liver lobe between adults].

BACKGROUND AND OBJECTIVE: Adult living donor liver transplantation has been established in an increasing number of transplant centres during the last few years. Donor safety and risks are important criteria influencing the further development. We report our experience with 43 adult-to-adult right lobe living donor liver transplantations. METHODS: 43 patients (mean age: 49,8 +/- 16,0 years; f:m = 14:29) with end-stage liver disease received a right lobe liver graft from an adult living donor (mean age: 42,4 +/- 13,4 years; f:m = 27:16) between December 1999 and December 2001. An approval by the local ethics committee was obtained prior to the start of the programme and each donation. RESULTS: None of the donors experienced fatal or long-term complications. The rate of surgical complications in donors (biliary leakage, bleeding) was 9 %. Actuarial recipient survival was 93 % after three months and 88 % after one year. Five patients had to be re-transplanted. Thus the actuarial 1-year graft survival was 79 %. Biliary complications occurred in 14 % of all recipients. CONCLUSION: According to our experience, living donor liver transplantation of the right hepatic lobe is a safe and effective procedure. Especially for patients in acute and chronic liver failure, who otherwise would have died on the waiting list, this approach offers a life-saving option.

Adult↗
PubMed2002

Concept for modular extracorporeal liver support for the treatment of acute hepatic failure.

Acute liver failure has a poor prognosis. The introduction of liver transplantation as a therapeutic option reduced mortality to 20-40%.With the growing disparity between the number of organ donations and the number of patients waiting for liver transplantation, efforts have been made to optimize the allocation of organs and to design extracorporeal methods to support the failing liver. The modular extracorporeal liver support is a concept for the treatment of hepatic failure. The CellModule is a multicompartment bioreactor for extracorporeal liver support therapy. The construction provides efficient integrated oxygenator functions and decentralized mass transfer is effected by a woven array of capillary systems. The bioreactor promotes primary human liver cells to spontaneous neo-formation of liver sinusoidal structures in vitro. Small capillary subunits, in which interwoven membrane links represent the liver lobuli, are simultaneously perfused. The used cell mass of 400-600 g enabled the clinical application of a liver lobe equivalent hybrid organ. The DetoxModule enables albumin-dialysis for removal of albumin-bound toxins; a DialysisModule for continuous veno-venous hemofiltration can be added to the system, in the case of hepato-renal failure.

Humans↗
PubMed2002

Primary human liver cells as source for modular extracorporeal liver support--a preliminary report.

Cell-based extracorporeal liver support is an option to assist or replace the failing organ until regeneration or until transplantation can be performed. The use of porcine cells or tumor cell lines is controversial. Primary human liver cells, obtained from explanted organs found to be unsuitable for transplantation, are a desirable cell source as they perform human metabolism and regulation. The Modular Extracorporeal Liver Support (MELS) concept combines different extracorporeal therapy units, tailored to suit the individual and intra-individual clinical needs of the patient. A multi-compartment bioreactor (CellModule) is loaded with human liver cells obtained by 5-step collagenase liver perfusion. A cell mass of 400 g - 600 g enables the clinical application of a liver lobe equivalent hybrid organ. A detoxification module enables single pass albumin-dialysis via a standard high-flux dialysis filter, and continuous veno-venuous hemodiafiltration may be included if required. Cells from 54 human livers have been isolated (donor age: 56 +/- 13 years, liver weight: 1862 +/- 556 g resulting in a viability of 55.0 +/- 15.9%). These grafts were not suitable for LTx, due to steatosis (54%), cirrhosis (15%), fibrosis (9%), and other reasons (22%). Out of 36 prepared bioreactors, 10 were clinically used to treat 8 patients with liver failure. The overall treatment time was 7-144 hours. No adverse events were observed. Initial clinical applications of the bioreactor evidenced the technical feasibility and safety of the system.

Bioreactors↗
PubMed2002

Analysis of allogeneic versus xenogeneic auxiliary organ perfusion in liver failure reveals superior efficacy of human livers.

PURPOSE: To compare the efficacy of allogeneic and xenogeneic extracorporeal liver perfusion (ECLP). METHODS: An Internet-based keyword search was performed in the established online databases. Univariate and multivariate analysis of variance (general linear method) were performed. RESULTS: Data from 198 patients were included in the statistical analysis, 142 of whom were treated by ECLP using porcine livers. Baboon livers were used in 29 patients, human livers in 14, and other or mixed species in 13 patients. Pig liver perfusions resulted in a 20% long-term-survival whereas the use of human livers was significantly more successful (survival rate (SVR) 43%, p<0.05). Baboon livers also revealed superior success (41%; p<0.05). Twenty-three patients were treated after 1991, 12 surviving long-term (52%). The latter all belonged to a group of 14 patients who received combined treatment consisting of ECLP and LTx (SVR-86% in this subgroup). CONCLUSION: Allogeneic ECLP was accompanied by significantly improved outcome compared with discordant xenogeneic ECLP. The role of hyperacute rejection in acute liver failure with reduced complement levels remains controversial. Physiologic disparity between pig and man may be the even more decisive determinant of outcome.

Animals↗
PubMed2002

Extracorporeal liver support: porcine or human cell based systems?

Initial results of the clinical use of primary porcine liver cells for extracorporeal liver support are being reviewed as the cell source is controversial. According to Eurotransplant data 20-25% of explanted donor livers are not transplanted, due to factors such as steatosis or cirrhosis. This number corresponds to the number of patients with acute liver failure who require bridging therapy to transplantation. Primary human liver cells from transplant discards can be isolated, purified and maintained in bioreactors and provide an alternative for cell-based extracorporeal liver support therapy. A four-compartment bioreactor enables recovery from preservation and isolation injury in a three-dimensional network of interwoven capillary membranes with integrated oxygenation, rendering the liver cells from these discarded donor organs viable for clinical utilization. Patient contact with additional animal-derived biomatrix and fetal calf serum can be avoided. The initiation of an in vitro cultivation phase allows cell stabilization, quality control, and immediate availability of a characterized system without cryopreservation. The hypothesis of this paper is that with appropriate logistics and four-compartment bioreactor technology, cells from human liver transplant discards can serve the demand for cell-based therapy, including extracorporeal liver support.

Animals↗
PubMed2001

Development of a hybrid liver support system.

Hybrid liver systems are being developed as temporary extracorporeal liver support therapy. The overview given here emphasizes the development of both hepatocyte culture models for bioreactors and of systems for clinical therapy. In vitro studies demonstrate long term external metabolic function in isolated primary hepatocytes within bioreactors. These systems are capable of supporting essential liver functions. Animal experiments verify the possibility of upscaling bioreactors for clinical treatment. However, since there is no reliable animal model for investigating the treatment of acute liver failure, the promising results obtained from these studies have limited relevance to human beings. The small number of clinical studies performed thus far are not sufficient to enable any conclusions concerning improvements in the therapy of acute liver failure. Although important progress has been made in the development of these systems, multiple hepatocyte culture models and bioreactor constructions are being discussed in the literature, indicating competition in this field of medical research. For the use of hepatocytes and sinusoidal endothelial cells in coculture, a bioreactor has been designed. The construction is based on capillaries for hepatocyte aggregate immobilization. Four separate capillary membrane systems, each permitting a different function, are woven in order to create a three-dimensional network. Cells are perfused via independent capillary membrane compartments. Decentralized oxygen supply and carbon dioxide removal with low gradients is possible. The parallel use of identical units enables easy upscaling. Initial studies on the use of discarded organs that are unsuitable for transplantation as a source for primary human liver cells seem to be promising.

Bioartificial Organs↗
PubMed2001

Experimental evaluation of a cell module for hybrid liver support.

Aim of the study was to evaluate a hybrid liver support system in a porcine model of acute liver failure, after hepatectomy. Pigs with a body weight of 70+/-18 kg underwent total hepatectomy and porto-cavo-caval shunting as well as ligation of the bile duct and the hepatic artery. Control animals were connected to the system (including capillary membrane plasma separation) containing a four compartment bioreactor with integral oxygenation and decentralized mass exchange but without liver cells. The treatment group received hybrid liver support with the same system including 370+/-42 g primary isolated porcine parenchymal liver cells in co-culture with hepatocyte nursing cells, tissue engineered to liver- like structures at high density. Treatment started after complete recovery from anesthesia and was performed continuously. A positive influence on peripheral vascular resistance and a reduced need of catecholamine dosage was observed in the treatment group. Hybrid liver support with a cell module upscaled for clinical application significantly prolonged survival time in animals after hepatectomy with the longest survival being 26 hours in the control group an 57 hours in the treatment group.

Animals↗
PubMed1999

Proposal of a new electromechanical total artificial heart: the TAH Serpentina.

A new type of energy converter for an electro-mechanical total artificial heart (TAH) based on the principle of a unidirectional moving motor is described. Named the TAH Serpentina, the concept consists of 2 major parts, a pendulum shaped movable element fixed on one side using a joint bearing and a special shaped drum cam. Pusher plates are mounted flexibly to the crossbar of the pendulum. A motor drives the special shaped drum cam linked to the pendulum through a ball bearing. The circular motion of the unidirectional moving brushless DC motor is transferred into the linear motion of the pendulum to drive the pusher plates. Using a crossbar with a variable length, the stroke of the pendulum and therefore the displaced blood volume is alterable. To achieve a variable length, an electric driven screw thread or a hydraulic system is possible. Comparable to the natural heart, cardiac output would be determined by frequency and stroke volume.

Electronics, Medical↗
PubMed1999

An unusual case of early pancreas graft loss.

Vascular thrombosis is the leading cause of nonimmunologic, technical graft loss following pancreas transplantation. An unusual case of early pancreas graft loss due to dissection of an atherosclerotic plaque -- presumably caused by clamping during implantation -- is described.

Adult↗
PubMedDate not supplied

Ovalis TAH: development and in vitro testing of a new electromechanical energy converter for a total artificial heart.

A new electromechanical energy converting system has been developed to yield an efficient and durable orthotopic total artificial heart (TAH). The energy converter we developed transforms the unidirectional rotational motion of the motor into a longitudinal forward-reverse movement of an internal geared oval, linked directly to pusher plates on both sides. To ensure a permanent positive connection between the drive gear and the internally geared wheel, a ball bearing runs inside an oval shaped guide track. Motor, gear unit, and conical pusher plates are seated between alternately ejecting and filling ventricles. The unidirectional motion of the brushless DC motor affords easier motor control, reduces energy demand, and ensures longer life of the motor when compared with a bidirectional motion system. In vitro testing has been performed on a mock circulation loop. The overall system efficiency of the TAH Ovalis was 27-39% (mean, 36%) for the pump output range of 2-7 L/min. The maximum output of 7 L/min can be obtained with a pump rate of 130 min(-1) and an afterload pressure of 140 mm Hg. For an average sized human with a mean cardiac output of 6 L/min at a mean aortic pressure of 120 mm Hg, 5 watts of input power would be required. The size of the prototype is 560 cm3, the weight is 950 g. Our first in vitro studies demonstrated the excellent efficiency and pump performance of this new electromechanical energy converter. The results prove the feasibility of this new concept's use as an energy converter for a total artificial heart.

Biomechanical Phenomena↗