Artificial and transplanted organs: movable parts and the unmoving law.
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Artificial Organs↗
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[Great potential of small RNAs: RNA interference and microRNA].
Double-stranded RNA (dsRNA) induces a sequence-specific silencing in eukaryotic cells. This silencing process beggins when long dsRNA is cleaved to 21 to 26 long small RNA by means of the RNAse III-type enzyme Dicer. These small dsRNA are included into silencing effector complexes, that are targeted to complementary sequences. Small RNA dependent gene silencing can be achieved by distinct mechanisms based depending mainly on the nature of target sequences and on the proteins present in the effector complex. The route of interference RNA (RNAi) begins when Dicer yields small interference RNA (siRNA) that bind to complementary mRNA for its degradation, forming the RISC complex. siRNA are naturally formed from transposons and dsRNA viruses during its replication, as well as from other bidirectional transcribed repetitive sequences. Some of the enzymes thar are part of the RNAi machinery, including Dicer, are encoded by multigene families in many species, that also play a role in other mechanisms of RND-dependent gene silencing. MicroRNA's (miRNA) are other small RNA's that can induce gene silencing at the mRNA level. These are formed in a general manner when Dicer process hairpin structures resulting from the transcription of non-coding sequences from plant and animal genomes. miRNA's are integrated into a RISC-like complex, after which, depending on their degree of complementarity with target mRNA, can either repress translation or induce mRNA degradation. miRNA-dependent silencing is essential for the development of multicellular organisms. Artificial RNAi induction by means of siRNA or miRNA is being used as a tool to inactivate gene expression in culture cells and in living organisms. This review focuses on the progress in the understanding of the mechanisms involved in gene regulation by RNA in animals and details some current efforts to apply theses phenomena as a tool in research and in the therapeutic of human diseases.
Humans↗
[Disposable polymer products for artificial cleansing of blood].
During artificial blood clearance, disposable articles are used for extracorporeal transportation of physiological fluids under sterile conditions and for normalizing action on blood in the acting elements of artificial organs. They allow improvement of clinical parameters, safety and accessibility of the technique of extracorporeal life support. A universal kit of arteries is proposed for artificial clearance.
Disposable Equipment↗
Artificial neural networks can distinguish novice and expert strategies during complex problem solving.
OBJECTIVE: To determine whether expert problem-solving strategies can be identified within a large number of student performances of complex medical diagnostic simulations. METHODS: Self-organizing artificial neural networks were trained to categorize the performances of infectious disease subspecialists on six computer-based clinical diagnostic simulation that used the sequence of diagnostic tests requested as the input data. Six hundred seventy-six student solutions to these problems were presented to these trained neural networks to determine which, if any, of the student solutions represented those of the experts. RESULTS: For each simulation, the expert performances clustered around one dominant output neurode, indicating that there were common problem-specific features associated with the experts' problem-solving performances. When the performances of students who also made correct problem diagnoses were tested on these expert-trained neural networks, 17% were classified as representing expert strategies, indicating that expert performance was a somewhat rare and inconsistent occurrence among the students. CONCLUSIONS: The ability to identify a small number of expert-like strategies within a large body of student performances may provide an opportunity to study the dynamics of complex learning at both individual and population levels as well as the emergence of medical diagnostic expertise.
Diagnostic Tests, Routine↗
Identification and discrimination of oral asaccharolytic Eubacterium spp. by pyrolysis mass spectrometry and artificial neural networks.
Curie-point pyrolysis mass spectra were obtained from 29 oral asaccharolytic Eubacterium strains and 6 abscess isolates previously identified as Peptostreptococcus heliotrinreducens. Pyrolysis mass spectrometry (PyMS) with cluster analysis was able to clarify the taxonomic position of this group of organisms. Artificial neural networks (ANNS) were then trained by supervised learning (with the back-propagation algorithm) to recognize the strains from their pyrolysis mass spectra; all Eubacterium strains were correctly identified, and the abscess isolates were identified as un-named Eubacterium taxon C2 and were distinct from the type strain of P. heliotrinreducens. These results demonstrate that the combination of PyMS and ANNs provides a rapid and accurate identification technique.
Bacterial Typing Techniques↗
Activation of prophenoloxidase with 2-propanol and other organic compounds in Drosophila melanogaster.
Activation with 2-propanol and other organic compounds of prophenoloxidase purified from pupae of Drosophila melanogaster was analyzed. A1, one of the two isozymes of the prophenoloxidase, could be activated with both an endogenous activating system and artificial organic compounds including alcohols. A1 was activated within 2 min after addition of 2-propanol. The phenoloxidase activity of A1, which had been activated with 2-propanol, decreased gradually by lowering the concentration of 2-propanol taking c 60 min to attain a low level, and the activity could be re-elevated at the re-introduction of 2-propanol. Thus the reversibility of the activation of A1 in response to the change of the concentration of 2-propanol in the activating mixture could be observed. Optimum concentration of 2-propanol for the rate of activation was 50%, optimum temperature was 30 degrees C and optimum pH was 7.5. The final level of the phenoloxidase activity, which had been activated with 2-propanol, was higher than that activated with the endogenous activating system. The activated state of A1 showed properties of a tyrosinase-type phenoloxidase. The results suggested that the activation of A1 with 2-propanol is caused by the reversible conformational change of the prophenoloxidase molecule.
1-Propanol↗
Mechanical test methods for biomedical membranes.
It is important to estimate the mechanical characteristics and strength of biomedical membrane. For this purpose, previously we have proposed several mechanical test methods for biomedical membranes. To establish the safety design for biomedical membrane, such as cellophane membrane for hemodialysis, it is important to estimate the viscoelastic characteristics of these materials. On the other hand, artificial biomedical membrane such as tympanic membrane, are subjected to noncontact internal air pressure under the membranous state. To estimate mechanical characteristics of such membrane, it is necessary to develop a well-simulated test under the gaseous pressure and the other mechanical test under the membranous state. In this paper, several test methods for these purposes were shown. Furthermore, results obtained by these methods were shown and related to clinical problems. These proposed test methods are quite different from the axial tensile test. But they are also important to estimate the mechanical property of biomedical membrane. Each result obtained by these test methods has its own significance. By selection of the most suitable test method for each purpose and revealing these mutual relations, safety design of artificial organs can be performed from the viewpoint of the strength.
Cellophane↗
[The first clinical experience with heart transplantation].
The article analyses the first clinical experience in orthotopic allotransplantation of the heart at the Scientific Research Institute of Transplantology and Artificial Organs, USSR Ministry of Health, in the period from October, 1986 to July, 1989 (26 transplantations of the heart and one two-stage transplantation of the heart with the use of "Poisk-10M" artificial heart for 3.5 days in the first stage). Eleven patients are alive. Follow-up periods: maximum over 2.5 years, minimum 3 months. Sixteen patients died in different periods (up to 12 months). Three-component therapy (cyclosporine A, methylprednisolone, azathioprine) was applied for immunosuppression. The authors analyse the problems of the selection of potential recipients (indications and contraindications) and donor, the optimum surgical techniques, complications of immunosuppressive therapy, and infectious complications. The first clinical experience in two-stage transplantation of the heart is analysed. The first experience in transplantation of the heart in patients allows the conclusion that the use of this method for the management of the terminal stage of congestive cardiac insufficiency is a reality.
Adult↗
The artificial heart: history and current status.
Twenty-years ago groups from California to Massachusetts were actively involved in the development of an artificial heart. From biomaterials development to biomedical power sources, the supporting industry and spin-off benefit was broad indeed. Young people were seeking careers in biomedical engineering and science. The National Institutes of Health was supporting artificial heart research at $10 to $12 million dollar levels. Groups at Andros, Inc. (now Baxter Novacor) and Stanford, Thoratec, Penn State and the Hershey Medical Center, Cleveland Clinic and the Division of Artificial Organs, the University of Utah, the Texas Heart Institute and the Baylor College of Medicine, Thermal Electron Corporation, and many more were the source of research and breakthrough development of pumps and systems for artificial hearts. We reported on performance criteria for an artificial heart pump at the First Biomechanics Symposium in 1973 [1]. By the beginning of the decade of the 90's, thousands of presentations had been made and manuscripts written reporting significant progress in the development of artificial heart pumps and systems. The Heart, Lung and Blood Institute of the National Institutes of Health was supporting an artificial heart contract research and development program at a level of $6 million dollars in 1991 [2]. Broad basic research grant activity also continues. The National Institutes of Health's artificial heart program received renewed support from the Institute of Medicine's special review in 1991 [3]. In December of 1992, the 16th Annual Cardiovascular Science and Technology Conference attracted over 500 attendees. This annual conference has provided a continuing forum for an update on progress in artificial heart development.
Animals↗
Sol-gel chemistry in medicinal science.
The sol-gel process is an inorganic polymerization process taking place in mild conditions, allowing the association of mineral phases with organic or biological systems. The possibility to immobilize drugs, enzymes, antibodies and even whole cells without loss of their biological activity led to the development of diagnostic tools, drug delivery carriers as well as new hosts for artificial organ design. These systems take profit from the wide variety of chemical compositions, dimensions and forms that can be achieved via sol-gel chemistry. Recent advances involve multi-functional "smart" devices combining biocompatibility, biological activity and stimuli-responsive materials. The design of such novel devices with significant added value when compared to current products is probably a key factor when foreseeing industrial developments of sol-gel materials in medicinal science.
Biocompatible Materials↗
Ethics in actual surgery. Ethics and organ transplantation.
Actual organ transplantation evokes more and more ethical questions. There is scarcity of donor organs. The waiting lists of potential recipients for organ transplantation are steadily growing as is the number of dead among the waiting patients. In Belgium the mortality rate of traffic victims during the first thirty days of hospital admission has been reduced by half. Among this group the number of potential cadaveric donor candidates is further reduced following complications of sustained intensive care. Shortage of cadaveric organs prompts some to select candidates for transplantation with exclusion of those considered responsible for their illness. Some centres incline to reconsider the definition of cerebral death by extending this notion to the irreversibly unconscious and therefore socially dead. Organ donation by living donors opens the way to commercialism specially in case of unrelated living donation. Living donors are often insufficiently informed about their risks and the final outcome of these transplantations. The use of implantable artificial organs should be the solution to many ethical problems. But some experience with the Jarvik heart as a temporary implant increases so far the shortage of donor heart supply and the number of patients on the waiting lists as well. It also excludes patients who became unsuitable for transplantation after complication of the Jarvik implantation. Xenotransplantation is largely under investigation. However, it is out of question that primates, which are threatened already with extinction should act as organ suppliers for mankind. Xenograft organs should be found in animals for food consumption, sufficient in number and more easily accepted as organ donors on ethical ground.
Accidents, Traffic↗
Monitoring system for the totally implantable ventricular assist system by use of sensors for virtual reality.
For the development of the totally implantable artificial organs, it is an important problem to monitor the conditions of the implantable devices, especially when used in clinical cases. In this study we used position sensors for the 3-dimensional (3-D) virtual reality (VR) system monitor an implantable artificial heart. The sensors used in the experiments were 3-space Fastrak (Polhemus, USA). The position sensors using electro-magnetic forces were attached to the inner actuating zone. Sensitivity of the position sensors was in the order of around 0.8 mm. By use of these VR position sensors, we could easily detect the six degrees of freedom as x,y,z, and pitch, yaw, roll of these sensors. Experimental evaluation using a model circulation loop and healthy adult goats was performed. Experimental results suggest that our newly developed implantable sensors for monitoring the implantable artificial heart system were useful for sensing driving condition, thus possibly useful for the implantable devices for clinical usage.
Animals↗
Induction cardiac pacing: a new approach.
A new approach to induction cardiac pacing using a "skin tunnel" transformer has been developed and used in a patient. Initial results are encouraging. If the system proves reliable in the long term it may have important applications in the delivery of power to implanted artificial organs.
Abdomen↗
Designing biomaterials to direct biological responses.
We have set forth a design strategy for creating biomimetic materials that direct the formation of tissue surrounding implants or regeneration within porous scaffolds. Our studies have established that heterogeneous mimetic peptide surfaces (MPS) containing both the -RGD- (cell-binding) and-FHRRIKA- (putative heparin-binding) peptides, unique to BSP, in the ratio of 75:25 (MPS II) or 50:50 (MPS III) proved to be more biologically relevant and specific for RCO cell function. The initial response of human osteoblast-like cells to these surfaces was mediated by the collagen (alpha 2 beta 1) and vitronectin receptors (alpha v beta 3), whereas the vitronectin receptor alone dominated longer-term events (> 30 min). MPS II and III surfaces enhanced cell spreading and long-term events such as mineralization of the extracellular matrix compared to homogenous peptide surfaces and controls. Furthermore, extensive mineralization of the ECM deposited by RCOs occurred when the peptide was coupled to an interfacial interpenetrating polymer network (IPN) that resisted protein deposition (i.e., non-specific adsorption) and fouling. Work on thermo-reversible P(NIPAAm-co-AAc) hydrogels demonstrated the ability to create materials that can be delivered to the body in a minimally invasive manner and support tissue regeneration. These hydrogels can be modified to incorporate biofunctional components such as the biomimetic peptides, theoretically enhancing their ability to foster tissue regeneration. These results suggest that biomaterials can be engineered to mimic ECM components of bone (e.g., various organs) by grafting peptides in the appropriate ratios of the cell and heparin-binding domains, and ultimately modulate the expression of the osteoblast cell phenotype. Approaches similar to the one presented in this work can be used to design materials for hybrid artificial organs and other tissues.
Amino Acid Sequence↗
Human organ transplantation.
In terms of rehabilitation and extended years of survival, transplantation is a good treatment if vital organs are affected by end-stage disease. Rejection is one of the most serious complications, although advances in molecular biology may well lead to specific immunosuppression with few or no side-effects. The unique metabolic functions of the heart, liver and kidney make it doubtful whether artificial replacements will become available in the foreseeable future. In the present state of knowledge, metabolic feedback between artificial organs probably cannot be accomplished, and organ transplantation is therefore likely to remain an evolving technology for many years to come.
Costs and Cost Analysis↗
Update on the total artificial heart.
There has been a quest for an artificial organ that can replace the heart for decades. Remarkable advances were made in the second half of the twentieth century in the fields of medicine and engineering that led to the development of several devices with the intention of totally replacing the human heart. Some of these devices, like the Jarvik artificial heart, were utilized initially as a permanent replacement for the failing heart. It became more successful as a bridge to heart transplantation (BTT) in the years that followed its introduction. Currently the CardioWest total artificial heart (TAH) is the only device in clinical use with the intention of bridging patients to heart transplantation. Two new TAHs are being developed with the intention of being used as an alternative to transplantation (ATT) or on a permanent basis. The next 100 years will bring revolutionary new designs and advances in the field of end stage heart disease that may only be ideas at the present time.
Heart Transplantation↗
[Auxiliary blood circulation and the artificial heart: forty years of development].
The article summarizes forty-year experience in working over the problem of the artificial heart and auxiliary blood circulation in Laboratory and later Research Institute of Transplantology and Artificial Organs. This work has resulted in the development of balloon pumps for intraaortic contrapulsation, the technique of balloon installation, and indications to its application. The results of the clinical application of the method in patients with various pathologies have been estimated. Preclinically, left ventricular bypass techniques have been tested on more than twenty models of membrane type artificial ventricles. The results of the clinical application of left ventricular bypass have been analyzed. The authors adduce data on the development of the thermomechanical implantable bypass system "Micron-M". After achieving 100-day survival of calves with an artificial heart, an artificial heart with external power supply was used as a "bridge" to heart transplantation, but there was only one patient in whom transplantation was performed. The authors consider development of implantable auxiliary blood circulation devices and the artificial heart to be of great prospective value.
Animals↗
[Immunology in clinical practice. XXIII. Xenotransplantation].
Currently xenotransplantation is being discussed on national and international levels as a possible solution to tranplantation waiting lists, in view of the lack of alternative therapies. In recent years, enormous progress has been made in the area of immunology, especially concerning hyperacute rejection. However, long-term survival is still fiction due to relatively unknown, sequential rejection processes. Moreover, it remains questionable if xenogeneic organs will function physiologically, especially if they are metabolically complex. A third problem is the possible infectious risk of xenotransplantation to the patient and the population. Regarding this hazard, various committees and policy reports demand clarity first before the initial clinical transplantations become fact. In the Netherlands, the government largely adopted an identical advice by the Health Council. Artificial organs and cloning developments indicate that xenotransplantation might merely be an intermediate station in the route to develop adequate treatment for patients with organ failure.
Animals↗