Showing papers in "Artificial Organs in 2002"

Improving the clinical patency of prosthetic vascular and coronary bypass grafts: the role of seeding and tissue engineering.

Abstract: In patients requiring coronary or peripheral vascular bypass procedures, autogenous vein is currently the conduit of choice. If this is unavailable, then a prosthetic material is used. Prosthetic graft is liable to fail due to occlusion of the graft. To prevent graft occlusion, seeding of the graft lumen with endothelial cells is undertaken. Recent advances have also looked at developing a completely artificial biological graft engineered from the patient's cells with properties similar to autogenous vessels. This review encompasses the developments in the two principal technologies used in developing hybrid coronary and peripheral vascular bypass grafts, that is, seeding and tissue engineering.

Powering an artificial heart: birth of the inductively coupled-radio frequency system in 1960.

Abstract: In mid-1960, our group initiated a research program focused on studying pain-free electromagnetic methods of furnishing energy to an implanted heart without piercing the skin. During the last half of 1960, we derived a detailed theoretical rationale for a radio frequency system involving inductive coupling between a thin, small, pancake-shaped coil on the surface of the chest and a similar coil either within the chest or, alternatively, subcutaneously. Having an efficiency of about 95%, the system was evaluated in dogs at 50 and 69 W levels, respectively. Thus was born what is now termed the transcutaneous energy transformer (TET).

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

Abstract: 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.

Design of a new pulsatile bioreactor for tissue engineered aortic heart valve formation.

Abstract: Evidence has been gathered that biomechanical factors have a significant impact on cell differentiation and behavior in in vitro cell cultures. The aim of this bioreactor is to create a physiological environment in which tissue engineered (TE) aortic valves seeded with human cells can be cultivated during a period of several days. The bioreactor consists of 2 major parts: the left ventricle (LV) and the afterload consisting of a compliance, representing the elastic function of the large arteries, and in series a resistance, mimicking the arterioles and capillaries. The TE aortic valve is placed between the LV and the compliance. With controllable resistance, compliance, stroke volume and frequency, and hydrodynamic conditions can be changed over a wide physiological range. This study resulted in a prototype of a compact pulsatile flow system for the creation of TE aortic valves. In addition a biocompatibility study of the used materials is performed.

Restitution of reaching and grasping promoted by functional electrical therapy.

Abstract: Functional electrical therapy (FET) is a new term describing a combination of functional electrical stimulation that generates life-like movement and intensive exercise in humans with central nervous system lesions. We hypothesized that FET can promote a significant recovery of functioning if applied in subacute stroke subjects. The study included 16 stroke subjects divided into a low functioning group (LFG) and a high functioning group (HFG) based on their ability to control wrist and fingers and randomly associated into FET and controls. The FET consisted of 30 min daily sessions during 3 weeks. The exercise comprised functional use of daily necessary activities (e.g., writing, using a telephone receiver, and drinking from a can). The outcome presented in this article is the upper-extremity function test performed before and after the therapy. The change in performance of the HFG group was significant. The number of successful repetitive movements in 2 min was doubled and 1.6 times increased for controls, and the time to perform the movement was decreased by 71% percent and by 36% in controls. In the LFG FET group, the difference in performance was the following. First, the number of tasks was increased from 0 to 6 (total of 11 tasks). Second, the averaged number of successful repetitive movements was increased from 0 to 3. The functional improvement in the FET LFG is probably not sufficient to make the more affected arm/hand effective for daily necessities; thus, the FET effects could deteriorate over a longer time. The subjects from the control LFG made only a marginal improvement. The follow-up for each subject will continue for 12 months after the beginning of the treatment.

Polyetherimide: a new membrane-forming polymer for biomedical applications.

Abstract: Membranes for biohybrid organs such as the biohybrid liver support system have to face 2 different environments, namely blood and tissue cells. Accordingly, the respective membrane surfaces must have optimal properties in terms of biocompatibility for blood or tissue. Flat membranes prepared by a phase inversion process from polyetherimide were modified by binding of tris-(hydroxymethyl)-aminomethane to obtain a surface with hydroxyl groups by binding of polyethylene imine to attach a hydrophilic macromolecule with amine groups useful as a spacer for later bonding of further ligands and by attachment of heparin. The binding of the different ligands was successful as monitored by different physicochemical methods. The blood response of plain polyetherimide was comparable to that of polyacrylonitrile, and it could be further improved by the binding of heparin. The tissue compatibility of polyetherimide and its different modifications was compared with commercial cell culture substrate membranes (Millicell) and found to be comparable for polyetherimide and even better after the modification with tris-(hydroxymethyl)-aminomethane. In conclusion, polyetherimide seems to be an interesting material for the production of membranes for application in biohybrid organ systems.

Denervated Muscles in Humans: Limitations and Problems of Currently Used Functional Electrical Stimulation Training Protocols

Abstract: Prior clinical work showed that electrical stimulation therapy with exponential current is able to slow down atrophy and maintain the muscle during nonpermanent flaccid paralysis. However, exponential currents are not sufficient for long-term therapy of denervated degenerated muscles (DDMs). We initiated a European research project investigating the rehabilitation strategies in humans, but also studying the underlying basic scientific knowledge of muscle regeneration from satellite cells or myoblast activity in animal experiments. In our prior study, we were able to show that high-intensity stimulation of DDMs is possible. At the beginning of training, only single muscle twitches can be elicited by biphasic pulses with durations of 120-150 ms. Later, tetanic contraction of the muscle with special stimulation parameters (pulse duration of 30-50 ms, stimulation frequency of 16-25 Hz, pulse amplitudes of up to 250 mA) can improve the structural and metabolic state of the DDMs. Because there are no nerve endings for conduction of stimuli, large-size, anatomically shaped electrodes are used. This ensures an even contraction of the whole muscle. Contrary to the current clinical knowledge, we were able to stimulate and train denervated muscle 15-20 years after denervation. The estimated amount of muscle fibers that have to be restored is about 2-4 million fibers in each m. quadriceps. To rebuild such a large number of muscle fibers takes up to 3-4 years. Despite constant stimulation parameters and training protocols, there is a high variation in the developed contraction force and fatigue resistance of the muscle during the first years of functional electrical stimulation.

Overview: end-stage renal disease in the developing world.

Abstract: Although the vast majority of patients with end-stage renal disease (ESRD) worldwide live in what is called the developing world, little is known about its epidemiology and management. With the current paucity of credible and adequately representative registries, it is justified to resort to innovative means of obtaining information. In this attempt, world-renowned leading nephrologists in 10 developing countries collaborated in filling a 103-item questionnaire addressing epidemiology, etiology, and management of ESRD in their respective countries on the basis of integrating available data from different sources. Through this joint effort, it was possible to identify a number of important trends. These include the expected high prevalence of ESRD, despite the limited access to renal replacement therapy, and the dependence of prevalence on wealth. Glomerulonephritis, rather than diabetes, remains as the main cause of ESRD with significant geographical variations in the prevailing histopathological types. The implementation of different modalities of renal replacement therapy (RRT) is inhibited by the lack of funding, although governments, insurance companies, and donations usually constitute the major sponsors. Hemodialysis is the preferred modality in most countries with the exception of Mexico where chronic ambulatory peritoneal dialysis (CAPD) takes the lead. In several other countries, dialysis is available only for those on the transplant waiting list. Dialysis is associated with a high frequency of complications particularly HBV and HCV infections. Data on HIV are lacking. Aluminum intoxication remains as a major problem in a number of countries. Treatment withdrawal is common for socioeconomic reasons. Transplantation is offered to an average of 4 per million population (pmp). Recipient exclusion criteria are minimal. Donor selection criteria are generally loose regarding tissue typing, remote viral infection, and, in some countries, blood-relation to the recipient in live-donor transplants. Cadaver donors are accepted in many countries participating in this survey. Treatment outcomes with different RRT modalities are, on the average, inferior to the internationally acknowledged standards largely due to infective and cardiovascular complications.

Computational Fluid Dynamics and Stent Design

Abstract: Stents are small, usually metallic tubes that are intended to prop open arteries blocked with atherosclerotic plaques. While stents have been used successfully in recent years, they still suffer from failure due to development of new tissue in stented segment (restenosis). Variations in the failure rates associated with different stent designs have led researchers to investigate the role of near-wall flow patterns. While there is no direct evidence yet, the patterns of flow stagnation as the blood flows past the stent struts may affect the restenosis process. Computational fluid dynamics (CFD) approaches are well suited for obtaining detailed information on stent flow patterns. Many CFD simulations make use of a two-dimensional model. The strong dependence of flow stagnation on stent strut spacing has been clearly demonstrated. These results have been employed to interpret the results of in vitro experiments designed to elucidate the mechanisms of restenosis.

Transcutaneous functional electrical stimulator "Compex Motion".

Abstract: Research groups in the field of functional electrical stimulation (FES) are often confronted with the fact that existing and commercially available FES stimulators do not provide sufficient flexibility and cannot be used to perform different FES tasks. The lack of flexibility of the commercial systems until now forced various FES research teams to develop their own stimulators. This paper presents a newly developed firmware and graphical programming software for the commercial Compex 2 stimulator which enhances the versatility and capabilities of the stimulator from a medical and therapeutic device to a neuroprosthesis and research tool. The new stimulator, called Compex Motion, can now be used to develop various custom-made neuroprostheses, neurological assessment devices, muscle exercise systems, and experimental setups for physiological studies. It can be programmed to generate any arbitrary stimulation sequence that can be controlled or regulated by various external sensors, sensory systems, or laboratory equipment. By interconnecting two or more Compex Motion stimulators, the number of stimulation channels can be increased to multiples of four channels, 8, 12, 16, 20, and so forth. The stimulation sequences and the control strategies are programmed and stored on exchangeable credit card-sized memory chip cards. The stimulator has four biphasic current-regulated stimulation channels and two general purpose analog input channels that can be configured to measure the output voltage of a variety of sensors such as goniometers, inclinometers, gyroscopes, or electromyographic (EMG) sensors. For real-time EMG control of the stimulation patterns, an EMG processing algorithm with software stimulation artifact blanking was implemented. The Compex Motion stimulator is manufactured by the Swiss company Compex SA and is currently undergoing clinical trials.

Interaction of the cardiovascular system with an implanted rotary assist device: simulation study with a refined computer model.

Abstract: In recent years, implanted rotary pumps have achieved the level of extended clinical application including complete mobilization and physical exercise of the recipients. A computer model was developed to study the interaction between a continuous-flow pump and the recovering cardiovascular system, the effects of changing pre- and afterloads, and the possibilities for indirect estimation of hemodynamic parameters and pump control. A numerical model of the cardiovascular system using Matlab Simulink simulation software was established. Data of circulatory system modules were derived from patients, our own in vitro and in vivo experiments, and the literature. Special care was taken to simulate properly the dynamic pressure-volume characteristics of both left and right ventricle, the Frank-Starling behavior, and the impedance of the proximal vessels. Excellent correlation with measured data was achieved including pressure and flow patterns within the time domain, response to varying loads, and effects of previously observed pressure-flow hysteresis in rotary pumps. Potential energy, external work, pressure-volume area, and other derived heart work parameters could be calculated. The model offers the possibility to perform parameter variations to study the effects of changing patient condition and therapy and to display them with three-dimensional graphics (demonstrated with the effects on right ventricular work and efficiency). The presented model gives an improved understanding of the interaction between the pump and both ventricles. It can be used for the investigation of various clinical and control questions in normal and pathological conditions of the left ventricular assist device recipient.

Physiologic Control Algorithms for Rotary Blood Pumps Using Pressure Sensor Input

Abstract: Hierarchical algorithms have been developed for enhanced physiologic control and monitoring of blood pumps using pressure inputs. Pressures were measured at pump inlet and outlet using APEX pressure sensors (APSs). The APS is a patented, long-term implantable, flow-through blood pressure sensor and designed to control implantable heart pumps. The algorithms have been tested using a Donavan circulatory mock-loop setup, a generic rotary pump, and LabVIEW software. The hierarchical algorithms control pump speed using pump inlet pressure as a primary independent variable and pump outlet pressure as a secondary dependent variable. Hierarchical control algorithms based on feedback from pressure sensors can control the speed of the pump to stably maintain ventricular filling pressures and arterial pressures. Monitoring algorithms based on pressure inputs are able to approximate flow rate and hydraulic power for the pump and the left ventricle.

Pediatric physiologic pulsatile pump enhances cerebral and renal blood flow during and after cardiopulmonary bypass.

Abstract: Controversy over benefits of pulsatile flow after pediatric cardiopulmonary bypass (CPB) continues. Our study objectives were to first, quantify pressure and flow waveforms in terms of hemodynamic energy, using the energy equivalent (EEP) formula, for direct comparisons, and second, investigate effects of pulsatile versus nonpulsatile flow on cerebral and renal blood flow, and cerebral vascular resistance during and after CPB with deep hypothermic circulatory arrest (DHCA) in a neonatal piglet model. Fourteen piglets underwent perfusion with either an hydraulically driven dual-chamber physiologic pulsatile pump (P, n = 7) or a conventional nonpulsatile roller pump (NP, n = 7). The radiolabeled microsphere technique was used to determine the cerebral and renal blood flow. P produced higher hemodynamic energy (from mean arterial pressure to EEP) compared to NP during normothermic CPB (13 +/- 3% versus 1 +/- 1%, p < 0.0001), hypothermic CPB (15 +/- 4% versus 1 +/- 1%, p < 0.0001) and after rewarming (16 +/- 5% versus 1 +/- 1%, p < 0.0001). Global cerebral blood flow was higher for P compared to NP during CPB (104 +/- 12 ml/100g/min versus 70 +/- 8 ml/100g/min, p < 0.05). In the right and left hemispheres, cerebellum, basal ganglia, and brainstem, blood flow resembled the global cerebral blood flow. Cerebral vascular resistance was lower (p < 0.007) and renal blood flow was improved fourfold (p < 0.05) for P versus NP, after CPB. Pulsatile flow generates higher hemodynamic energy, enhancing cerebral and renal blood flow during and after CPB with DHCA in this model.

Computational flow modeling in hollow-fiber dialyzers.

Abstract: A three-dimensional finite volume model of the blood-dialysate interface over the complete length of the dialyzer was developed. Different equations govern dialyzer flow and pressure distribution (Navier-Stokes) and radial transport (Darcy). Blood was modeled as a non-Newtonian fluid with a viscosity varying in radial and axial direction determined by the local hematocrit, the diameter of the capillaries, and the local shear rate. The dialysate flow was assumed to be an incompressible, isothermal laminar Newtonian flow with a constant viscosity. The permeability characteristics of the membrane were calculated from laboratory tests for forward and backfiltration. The oncotic pressure induced by the plasma proteins was implemented as well as the reduction of the overall permeability caused by the adhesion of proteins to the membrane. From the calculated pressure distribution, the impact of flow, hematocrit, and capillary dimensions on the presence and localization of backfiltration can be investigated.

Modular extracorporeal liver support.

Abstract: Modular extracorporeal liver support (MELS) is an integrative concept for the treatment of hepatic failure with appropriate extracorporeal therapy units tailored to suit the actual clinical needs of each patient. The CellModule is a specific bioreactor charged with primary human liver cells harvested from human donor livers found to be unsuitable for transplantation due to steatosis, cirrhosis, or traumatic injury. The DetoxModule enables albumin dialysis for the removal of albumin-bound toxins, reducing the biochemical burden of the liver cells and replacing the bile excretion of hepatocytes in the bioreactor. A DialysisModule for continuous venovenous hemofiltration can be added to the system if required in hepatorenal syndrome.

Tissue engineered heart valves: autologous cell seeding on biodegradable polymer scaffold.

Abstract: We previosly reported on the successful creation of tissue-engineered valve leaflets and the implantation of these autologous tissue leaflets in the pulmonary valve position. Mixed cell populations of endothelial cells and fibroblasts were isolated from explanted ovine arteries. Endothelial cells were selectively labeled with an acetylated low-density lipoprotein marker and separated from fibroblasts using a fluorescent activated cell sorter. A synthetic biodegradable scaffold consisting of polyglycolic acid fibers was seeded first with fibroblasts then subsequently coated with endothelial cells. Using these methods, autologous cell/polymer constructs were implanted in 6 animals. In 2 additional control animals, a leaflet of polymer was implanted without prior cell seeding. In each animal, using cardiopulmonary bypass, the right-posterior leaflet of the pulmonary valve was resected completely and replaced with an engineered valve leaflet with (n = 6) or without (n = 2) prior cultured cell seeding. After 6 h and 1, 6, 7, 9, and 11 weeks, the animals were sacrificed and the implanted valve leaflets were examined histologically, biochemically, and biomechanically. Animals receiving leaflets made from polymer without cell seeding were sacrificed and examined in a similar fashion after 8 weeks. In the control animals, the acellular polymer leaflets were degraded completely leaving no residual leaflet tissue at 8 weeks. The tissue-engineered valve leaflet persisted in each animal in the experimental group; 4-hydroxyproline analysis of the constructs showed a progressive increase in collagen content. Immunohistochemical staining demonstrated elastin fibers in the matrix and factor VIII on the surface of the leaflet. The cell labeling experiments demonstrated that the cells on the leaflets had persisted from the in vitro seeding of the leaflets. In the tissue-engineered heart valve leaflet, transplanted autologous cells generated proper matrix on the polymer scaffold in a physiologic environment at a period of 8 weeks after implantation.

Computational fluid dynamics and vascular access.

Abstract: Anastomotic intimal hyperplasia caused by unphysiological hemodynamics is generally accepted as a reason for dialysis access graft occlusion. Optimizing the venous anastomosis can improve the patency rate of arteriovenous grafts. The purpose of this study was to examine, evaluate, and characterize the local hemodynamics and, in particular, the wall shear stresses in conventional venous end-to-side anastomosis and in patch form anastomosis (Venaflo) by three-dimensional computational fluid dynamics (CFD). We investigated the conventional form of end-to-side anastomosis and a new patch form by numerical simulation of blood flow. The numerical simulation was done with a finite volume-based algorithm. The anastomotic forms were constructed with usual size and fixed walls. Subdividing the flow domain into multiple control volumes solved the fundamental equations. The boundary conditions were identical for both forms. The velocity profile of the patch form is better than that for the conventional form. The region of high static pressure caused by flow stagnation is reduced on the vein floor. The anastomotic wall shear stress is decreased. The results of this study strongly support patch form use to reduce the incidence of intimal hyperplasia and venous anastomotic stenoses.

Intravenous ascorbic acid administration for erythropoietin-hyporesponsive anemia in iron loaded hemodialysis patients.

Abstract: Intravenous ascorbic acid administration (IVAA) could override recombinant human erythropoietin (rHuEPO) resistance in hemodialysis patients with iron overload. We investigated the hematopoietic response to IVAA in iron-overloaded hemodialysis patients. We included 36 patients whose ferritin levels were higher than 500 microg/L and who needed more than 100 U/kg/week of rHuEPO. The study included an initial phase (500 mg IVAA twice weekly was administered to all of the patients for 8 weeks) and a maintenance phase (patient groups were formed; Group 1 received IVAA 500 mg/week for 8 weeks and Group 2 received no therapy). We observed a significant increase in hematocrit and transferrin saturation and a decrease in the percentage of hypochromic red cells and ferritin levels at the end of the initial phase. The total weekly-required rHuEpo dose and rHuEpo/hemoglobin also fell significantly after the initial phase. The response remained stable in patient groups during the maintenance phase. In 6 nonresponders, the hypochromic red cells were <10%. In conclusion, IVAA effectively overrides rHuEPO resistance in iron-overloaded hemodialysis patients.

The microsystems based visual prosthesis for optic nerve stimulation.

Abstract: The microsystems based visual prosthesis (MiViP) visual prosthesis generates visual perceptions well below safety and stimulator saturation limits. These perceptions, called phosphenes, are of reasonably small size and are broadly distributed in the visual field. They can thus be used to convey useful visual information. Psychophysical evaluations are being performed in order to assess the implantee's benefits in the use of the MiViP optic nerve visual prosthesis. In a pattern-recognition task, the performance improved regularly with practice with an increasing score and a decreasing delay to recognition. These observations open the way toward an evaluation of general mobility improvement with the portable system. In conclusion, the results obtained so far still support the potential usefulness of the optic nerve visual prosthesis. A low-resolution artificial vision can be expected from the prosthesis after extensive training.

Numerical calculation of hemolysis levels in peripheral hemodialysis cannulas.

Abstract: Hemolysis in extracorporeal life support systems presents an underestimated problem. In this article, we investigate the hemolytic potential of peripheral hemodialysis cannulas numerically. An axisymmetrical finite element model of 3 cannula sizes was built (13G, 14G, and 16G) that was refined sufficiently in the vicinity of the cannula tip to compute accurately scalar shear stresses. Scalar shear stresses were utilized in Giersiepen's equation to calculate the red blood cell damage (RBD) along streamlines. The streamlines were chosen such that they bound a percentage of the blood flow through the cannula. By integration of the RBD results, the total damage of the cannula was determined and expressed in modified index of hemolysis for comparison with published results. Calculated RBD was overestimated by Giersiepen's equation. The ranking of the cannulas according to their hemolytic potential was preserved. This indicates that power-law equations may be suited for hemolysis prediction of laminar flow devices.

A stimulator for functional activation of denervated muscles.

Abstract: In recent years various studies proved that electrical stimulation can improve contractile capability and restore muscle function in long-term denervated degenerated muscles. The low excitability of the muscle cells at the initial stage of training and surrounding connective tissue, acting as an electrical shunt, require special stimulation parameters. Until now, no appropriate devices (stimulators) are commercially available. Therefore, we were forced to design our own stimulators. The control unit of the stimulators is based on a microprocessor for maximum flexibility regarding the generation of the parameters such as pulse amplitudes, pulse width, frequency, stimulation times, ramps, and so on. In addition, the microprocessor design allows recording of compliance data such as stimulation date, time, duration, and used programs. The constant voltage output stage of the stimulator is able to generate biphasic charge balanced stimulation impulses with a pulse width of 1 to 300 ms, voltage amplitudes up to +/-80 V (160 VPP), and stimulation currents up to 250 mA. To prevent direct current due to inexact charge compensation, the electrode outputs are decoupled capacitively. Simultaneous 2 channel stimulation with independent intensity levels is possible. The stimulators are programmed using a notebook or a personal digital assistant via infrared serial interface. This concept guarantees the application of correct stimulation parameters because the patient has only access to parameters that are preprogrammed for him in the outpatient clinic. For the home based training, access is limited to variation of intensity within preprogrammed limits. For safety reasons, the portable unit is powered by an internal rechargeable battery. High efficiency switched voltage regulators are used to provide the different required voltage levels while ensuring an acceptable operating time of the stimulator.

Numerical investigation of the effect of blade geometry on blood trauma in a centrifugal blood pump.

Abstract: Fluid dynamic forces in centrifugal blood pump impellers are of key importance in destruction of red blood cells (RBCs) because high rotational speed leads to strong interaction between the impeller and the RBCs. In this paper, three-dimensional models of five different blade geometries are investigated numerically using the commercial software CFX-TASCflow, and the streaklines of RBCs are obtained using the Lagrangian particle tracking method. In reality, RBCs pass through the pump along complicated paths resulting in a highly irregular loading condition for each RBC. In order to enable the prediction of blood damage under the action of these complex-loading conditions, a cumulative damage model for RBCs was adopted in this paper. The numerically simulated percent hemoglobin (%HB) released as RBCs traversed the impeller and volute was examined. It was observed that the residence time of particles in the blade passage is a critical factor in determining hemolytic effects. This, in turn, is a function of the blade geometry. In addition, it was observed that the volute profile is an important influence on the computed HB% released.

Posttransplant infections in the tropical countries.

Abstract: Over half of all renal transplant recipients in the tropical countries develop a serious infection at some point in the posttransplant period and 20% to 40% of them succumb to these infections. Many of these infections are endemic to the region. A multitude of factors including unhygienic conditions, hot and humid climate, late presentation, lack of knowledge about the spectrum of organisms in these areas, scanty diagnostic techniques, and high cost of lifesaving antimicrobial agents contribute to this dismal outcome. Tuberculosis is observed in 10% to 15% of transplant recipients. Pleuropulmonary disease is most frequent, but the commonly employed tests are seldom helpful in the diagnosis. Bronchoalveolar lavage is very sensitive in early detection of this infection and allows timely institution of specific therapy. Hepatitis virus infections are generally acquired before transplant, and viral replication is accelerated under the effect of immunosuppressive therapy leading to chronic liver disease. Cytomegalovirus (CMV) disease has shown a fourfold increase after introduction of cyclosporine to the immunosuppressive regimes at our center. Coinfection with other bacteria or fungi is frequent in CMV-infected allograft recipients. Opportunistic fungal infections are seen in less than 10% of allograft recipients, but this figure is likely an underestimate. The frequently encountered fungal infections include Candida, Aspergillus, Cryptococcus, and Mucor. Fungal infections carried a high mortality of over 65% at our center. The protean manifestations of the opportunistic infections and nonavailability of sensitive diagnostic tests in most centers in the underdeveloped countries often delay the diagnosis and institution of therapy.

An implantable two channel drop foot stimulator: initial clinical results

Abstract: This article reports preliminary results of pilot studies of a new implantable two channel drop foot stimulator. The stimulator consists of an externally worn transmitter inductively coupled to an implanted receiver unit located in the lower leg, lateral and distal to the knee. The receiver is connected to electrodes located under the epineurium of the deep and the superficial peroneal nerves. Stimulation is triggered by detection of heel lift and terminated at heel strike in a manner similar to surface mounted systems. The location of the electrodes allows for a degree of selectivity over the resultant moment about the ankle joint that is not possible with surface stimulation of the common peroneal nerve. The two subjects used the stimulator on a regular basis and showed increases in walking speed of between 10% and 44% when compared to their baseline measurements. Isometric tests have demonstrated that the stimulator allows selective and repeatable stimulation of ankle joint muscles.

Predicting membrane oxygenator pressure drop using computational fluid dynamics.

Abstract: Three-dimensional computational fluid dynamic (CFD) simulations of membrane oxygenators should allow prediction of spatially dependent variables and subsequent shape optimization. Fiber bed complexity and current computational limitations require the use of approximate models to predict fiber drag effects in complete device simulations. A membrane oxygenator was modified to allow pressure measurement along the fiber bundle in all cardinal axes. Experimental pressure drop information with water perfusion was used to calculate the permeability of the fiber bundle. A three-dimensional CFD model of a commercial membrane oxygenator was developed to predict pressure drops throughout the device. Darcy's Law was used to account for the viscous drag of the fibers and was incorporated as a momentum loss term in the conservation equations. Close agreement was shown between experimental and simulated pressure drops at lower flow rates, but the simulated pressure drops were lower than experimental results at higher flows. Alternate models of fiber drag effects and flow field visualization are suggested as means to potentially improve the accuracy of the flow simulation. Computational techniques coupled with experimental verification offer insight into model validity and show promise for the development of accurate three-dimensional simulations of membrane oxygenators.

Levamisole treatment enhances protective antibody response to hepatitis B vaccination in hemodialysis patients.

Abstract: Hemodialysis shows a high risk for hepatitis B infection, and hepatitis B virus (HBV) vaccination has now become a routine procedure. Unfortunately, 40% to 50% of hemodialysis patients do not have adequate protective antibodies against the HBV vaccination which is thought to be due to depressed cell mediated immunity. Levamisole has been reported to stimulate depressed T-cell activity and enhance B lymphocyte function and restore delayed hypersensitivity reactions in immune-depressed patients. We studied the effects of levamisole, an immunomodulatory agent, on the protective antibody response of hemodialysis patients to the HBV vaccination. Our hemodialysis patients with negative anti-HBs antibody routinely received 40 microg doses of recombinant HBV vaccine intramuscularly at 0, 1, and 6 months, and we followed serum anti-HBs levels. Patients with a serum antibody level of >10 mIU/ml were considered as responders. Study groups were classified as follows. Group 1 was comprised of 96 chronic hemodialysis patients with negative anti-HBs and HBV core antibody (52 male, 44 female, mean age of 45 +/- 15 years and mean hemodialysis duration of 46 +/- 40 months) who received HBV vaccination; 55 patients (57%) were found to be responders. Group 2 was comprised of 19 randomly selected patients who had never received hepatitis B vaccine (13 male, 6 female, mean age of 42 +/- 14 years, mean duration of hemodialysis 31 +/- 27 months) and who were started on an HBV vaccination protocol with levamisole per os 80 mg after each hemodialysis session for 4 months and followed up on serum anti-HBs levels. Seventeen of the patients completed this levamisole treatment. Fourteen of the 17 patients had the levels of the protective serum antibody indicating a higher response rate when compared with patients who did not receive levamisole (82% versus 57%, respectively, p < 0.05). Group 3 was comprised of 19 patients randomly selected from persons who did not respond to previous vaccination programs (10 male, 9 female, mean age of 51 +/- 14 years, mean duration of hemodialysis 41 +/- 31 months). A second HBV vaccination program was started with the same levamisole protocol. In this group, 18 patients completed this treatment model. Fourteen of them responded to the vaccination model. In Group 4, a second HBV vaccination program was applied without levamisole to 20 randomly selected persons who did not respond to the previous routine vaccination program (12 male, 8 female, mean age of 53 +/- 17 years, mean duration of dialysis 51 +/- 38 months). Only 3 of them responded to a second vaccination program. Comparing Group 3 with Group 4, there was a higher responder rate to HBV vaccination (77% versus 15%, respectively, p < 0.0001). These results show that levamisole treatment increases the response rate to the first HBV vaccination and of the previously unresponsive cases by modulating possible cellular immune response.

Nonlinear Controller for Ventricular Assist Devices

Abstract: This paper presents the design of a gain-scheduled proportional integral (PI) feedback controller for ventricular assist devices to maintain physiologically motivated perfusion. The selected control objective is to maintain an average differential pressure deltaP between the left ventricle and the aorta. Computer simulations for different pathological conditions, ranging from the normal heart to left heart asystole, and a wide range of physiological scenarios, ranging from rest to strenuous exercise, were used to validate the performance of the controller and the effectiveness of the selected control objective in ensuring physiologically adequate perfusion under different clinical and cardiac demand conditions.

Functional analysis of the tissue-engineered stomach wall.

Abstract: We have established a method for in situ tissue engineering of the stomach in a canine model using an acellular collagen scaffold graft. The current study was conducted to evaluate the functional aspects of the tissue-engineered stomach wall. The anterior wall of the stomach in beagle dogs was replaced with a collagen sponge scaffold measuring 4 x 4 cm. At 16 weeks after implantation, the animals were sacrificed and the stomach specimens were evaluated immunohistochemically and physiologically. Regeneration of the proton pump and thin muscle layer, which are essential for mechanical and chemical digestion by the stomach, was observed in the tissue-engineered gastric tissue. However, acetylcholine-induced contraction was not observed in the tissue-engineered stomach wall. Although there is still room for improvement, the tissue-engineered stomach wall had a highly organized structure, and it is anticipated that this approach could eventually become an alternative for stomach reconstruction after gastrectomy.

Systemic consequences of ventricular assist devices: alterations of coagulation, immune function, inflammation, and the neuroendocrine system.

Abstract: Implantable ventricular assist devices have proven efficacious as a bridge to transplantation and as a bridge to recovery. Although current indications for use of assist devices are somewhat limited, they are likely to expand in the upcoming years, including their use as destination therapy for end-stage heart failure. Recipients of assist devices, however, are prone to certain device-specific complications, including excessive postoperative bleeding, late propensity for thromboembolism, infections, and systemic inflammation, which may contribute to end-organ dysfunction. This article reviews the systemic biochemical alterations underlying these clinical phenomena. As assist devices are increasingly used, better understanding of these systemic perturbations is imperative.

A prototype HeartQuest ventricular assist device for particle image velocimetry measurements.

Abstract: The objective of this study is to fully characterize the flow within the HeartQuest ventricular assist device (VAD), a magnetically levitated centrifugal VAD, using particle image velocimetry (PIV) to identify regions of potential high shear or stagnation and validate and refine computational models of the flow. An acrylic model of the pump was designed and constructed to allow optical access into all interior regions of the pump. The geometry of the exterior housing and the use of a novel working fluid make quantitative measurements of velocity within the exit volute, blade passage, cut-water, blade tip clearance, and pump inlet possible. Highly accurate velocity measurements using particle PIV have been made in one region (the inlet elbow), and measurements in the other critical regions of the pump will be made. These measurements are used for investigation of regions with potential for hemolysis resulting from high shear stress or with potential for thrombosis caused by recirculation or stagnation. Quantitative velocity data are also needed for comparison with computational fluid dynamics (CFD) models of the VAD. In this study, experiments have again proven to be an essential complement to CFD for thorough investigations of the flow inside the pump.