bluuebunny/crossref_metadata_2025 huggingface dataset:
Origins of differentiation via phenotypic plasticity
Authors: Schlichting Carl D.
Published: March 2003

SUMMARY How cell types of multicellular organisms came to be differentiated is still an open issue. Here I offer a model that posits that the origins of some cell differentiation patterns were originally passive outcomes of environmental effects. As cells' contact with the external environment was diminished, their patterns of gene expression were altered, due to changes in concentrations of externally supplied substances. Later, as multicellular growth continued, the relationships of cell layers to each other shifted, producing concentration gradients of signaling molecules. These gradients emanated both from the external cell layer toward the inside and from internal cell layers to adjacent layers. In this scenario then, differentiation arose initially as a by‐product of the changing patterns of gene expression and of the complex mixtures and changing concentrations of substances passing among layers. Subsequent selection would operate to stabilize the expression patterns in those cell layers whose phenotypes provide a fitness advantage to the organism.
Effect of High Concentrations of Bile Acids on Cultured Hepatocytes
Authors: Noto Hiromitsu , Matsushita Michiaki , Koike Masahiko , Takahashi Manabu , Matsue Hirokazu , Kimura Jun , Todo Satoru
Published: March 2003

High concentrations of bile acids have been reported as injurious to hepatocytes. We report the influence of various combinations of bile acids on the liver‐specific function of cultured rat hepatocytes. Using 4 bile acids (glycocholate [GC], taurocholate [TC], glycohenodeoxycholate [GCDC], and taurochenodeoxycholate [TCDC]), we obtained 6 bile‐acid mixtures, each containing equal amounts of 2 bile acids (total bile acids [TBA], 2 mM). Changes in gluconeogenesis, ureagenesis, DNA contents, medium alanine aminotransferase, and morphologies were compared among the paired bile acid compositions by measuring the C/CDC ratio ([GC + TC]/[GCDC + TCDC]) of each. In terms of their relative impairments of ureagenesis from greatest to least, the acids were GCDC, TCDC, and GC, which was almost the same as TC. When the C/CDC ratio was 0, the values of all parameters measured deteriorated. When the C/CDC ratio was 1 in the presence of 1 mM GCDC, only the rate of ureagenesis was diminished. When the C/CDC ratio was infinite, no hepatocellular injury was observed. GCDC and TCDC, together or separately, showed significant hepatocellular injury when the TBA concentration was 2 mM.
Centralized On‐Line Hemodiafiltration System Utilizing Purified Dialysate as Substitution Fluid
Authors: Sato Takashi , Koga Nobuhiko
Published: March 2003

We followed the guidelines of the Kyushu Society for Hemodiafiltration (HDF) Therapy on the purification of dialysate used as substitution fluid and clinically applied HDF using only 20 L or 15 L of substitution fluid in the pre‐ or postdilution mode, respectively. We used a centralized on‐line HDF system consisting of a novel multi‐patient dialysate delivery system applying 3 endotoxin (ET) removal filters in series, maintaining the ET level within the criteria limit below 1.0 IU/L (measured at the first filter outlet to be 0.1 IU/L and after the third filter to be below the sensitivity limit) irrespective of the fluctuation in the ET level of the tap water. Low molecular weight proteins (β2‐microglobulin, prolactin, α1 ‐micro‐globulin, and α1‐acid glycoprotein) were more effectively removed in this HDF system than in conventional hemodialysis (HD) using the same dialyzer as that in the HDF system, and the removal of these proteins in the HDF system was enhanced as their molecular weights increased. The clinical effect of the HDF system was demonstrated by a decrease in joint pain accompanied by improvement in joint motion in 6 dialysis patients followed over the long term (100 weeks).
Coronary Vascular Bed Perfusion with a Polyethylene Glycol‐Modified Hemoglobin‐Encapsulated Liposome, Neo Red Cell, in Rats
Authors: Nakai Kunihiko , Usuba Akira , Ohta Toshio , Kuwabara Mikinori , Nakazato Yoshikazu , Motoki Ryoichi , Takahash Tsuneo A.
Published: March 2003

Whether hemoglobin (Hb) encapsulated liposomes have vasoconstrictive activity remains controversial. We therefore examined the vascular activity of a liposome Hb, Neo red cell (NRC), in a simple in vitro model of Langendorff perfusion of the rat heart using Krebs‐Henseleit (KH) solution as the perfusate. In the KH solution, NRC (Hb at 1 mg/ml), however, induced an immediate and abnormal increase in perfusion pressure. Histological examinations revealed that embolisms were the likely cause of this disturbance. Inorganic crystals formed by the mixing of NRC with the perfusate were a possible source of the embolisms. We found that the addition of bovine serum albumin to the perfusate was effective in avoiding embolic events. This protocol was used to compare the vasoconstrictive properties of unmodified bovine Hb and NRC. Unmodified bovine Hb (1 mg/ml) caused an increase in perfusion pressure and a decrease in the duration of bradykinin‐induced relaxation. In contrast, NRC (Hb at 1 mg/ml) had no such vasoconstrictive effects. These results provide the first information regarding perfusion of the circulatory vascular bed by NRC and further evidence that the encapsulation of Hb into liposomes is an effective approach to modulate Hb‐related vasoconstrictive activity.
Isolated Kidney Controlled Perfusion with True Physiological Pulsatile Waveform
Authors: Del Cañizo  , Tejedor  , Lledó  , Radvan  , Desco  , Dulín  , Holberndt  , Hernández C. , García‐Barreno
Published: March 2003

A computer controlled perfusion system has been developed to study the behavior of perfused kidneys in several conditions. The system is designed to perform kidney perfusions at constant pressure and low temperature (about 4°C). We compared 2 types of perfusion pumps, a classical roller pump widely used in hemodialysis circuits and a vacuum powered tubular pump with active valves developed by our group and able to produce a flow pattern very similar to the pulse wave in the human circulatory system. In this preliminary study, we show the hydrodynamics obtained with both pumps in isolated hypothermic kidneys perfused with this system. The different flow patterns with both pumps seem to determine differences in the preservation conditions of the kidney.
Prediction of Anticoagulation During Hemodialysis by Population Kinetics and an Artificial Neural Network
Authors: Smith Brian P. , Ward Richard A. , Brier Michael E.
Published: March 2003

All systems currently used for routine hemodialysis require heparin administration to prevent blood clotting in the extracorporeal circuit. We tested the hypothesis that population‐based statistical techniques can be used to predict heparin concentrations during routine hemodialysis. Two predictive models were developed, one based on nonlinear mixed effects modeling (NONMEM) and the other on a multilayer perceptron neural network. Serial clotting time data were obtained from forty‐nine patients and used to develop the models. The models were used to predict the clotting times of 70 patients in a prospective test. We determined that the neural network provided greater precision, had fewer outliers in its predictions, and did not have the model misspecification in bolus administration that the NONMEM predictions demonstrated. A final NONMEM model was developed using all data from 119 patients to identify important covariates for predicting the heparin pharmacodynamic parameters, volume of distribution, and clearance. Both the volume of distribution and clearance increased following the initiation of dialysis and as the patient's baseline clotting time increased. The volume of distribution also increased as the patient's weight increased but was decreased by smoking and diabetes. Population‐based statistical techniques may provide a useful alternative to existing methods for prescribing heparin.
Estimation of the Native Cardiac Output from a Rotary Blood Pump Flow: In Vitro Study
Authors: Nakata Kin‐ichi , Ohashi Yukio , Tayama Eiki , Ohtsuka Goro , Takami Yoshiyuki , Mueller Juergen , Glueck Julie , Nosé Yukihiko
Published: March 2003

Abstract The rotary blood pump will be an implantable left ventricular assist device (LVAD) in the near future. However, the best control method and the interrelationship between the rotary blood pump and native heart functions are unclear. An estimation was made of the native heart cardiac output from the change of an LVAD's outflow waveform. The mock circulation loop was composed of an aortic compliance chamber, left arterial chamber, total artificial heart as a native heart, and a rotary blood pump that was placed as an LVAD with left ventricular drainage. The fast Fourier transform (FFT) technique was utilized to analyze the LVAD's outflow waveform and calculate the pulse power index (PPI) to examine a relation between the PPI and total artificial heart (TAH) output. The PPI increased with the increase of the TAH output; there was a positive correlation, and there was an inverse correlation between the PPI and the assist ratio. From this viewpoint, an estimation of the pulsatility change of the LVAD's outflow wave may indicate the native cardiac output.
Development of a Flow Estimation and Control System of an Implantable Centrifugal Blood Pump for Circulatory Assist
Authors: Wakisaka Yoshinari , Okuzono Yasuki , Taenaka Yoshiyuki , Chikanari Kenichi , Endo Seiko , Masuzawa Toru , Takano Hisateru
Published: March 2003

A bypass flow rate estimation and control system (BECS) for an implantable centrifugal blood pump (ICBP) has been developed in our institute. The estimated flow rate (EF) of the ICBP was derived from the electric power consumption, the rotating speed of a motor, and the blood viscosity presumed by the hematocrit and body temperature. The error in the EF was 0.5 ± 0.4 L/min in in vivo experiments for 40 days. The rotating speed of the motor was controlled automatically every 200 ms to bring the EF in accord with the desired flow rate (DF). The reactivity and accuracy of the BECS were investigated in in vitro and in vivo experiments. The ICBP was operated by the BECS in a mock circuit in parallel with a pulsatile ventricular assist device (PVAD) to simulate left heart bypass. The reactivity was evaluated by changing the DF from 7 L/min to 5 L/min at an afterload of 160/97 mm Hg. To evaluate the accuracy of the BECS, the ICBP was driven under the aortic pressure of 110/85 mm Hg in the abdominal wall of an adult goat (70 kg). The DF was set at 5 L/min for 4 min for the goat in an awake condition. It took 13 s to change the flow rate in the in vitro experiment. The measured flow rate (MF) was maintained at 5.0 ± 0.2 L/min by the BECS in vivo. In conclusion, the BECS has moderate reactivity and accuracy.
Retrieval Analysis of Mechanical Heart Valves: Impact on Design and Clinical Practice
Authors: Cromheecke Manon E. , Overkamp Peter J.B. , De Mol Bas A.J.M. , Van Gaalen Geerda L. , Becker Anton E.
Published: March 2003

Explanted mechanical heart valves were examined nondestructively, and the findings were related to guidelines, technical reports, and other information to judge the risk of failure and its possible impact on valve design and clinical practice. Diagnoses for single valves could be made, but risks and rates of failure for patient populations could not be predicted due to insufficient information concerning the manufacturing process and valve and patient numbers. Based on the results of this study and the principle that decisions on recalls and patient counseling must be based on scientific knowledge rather than on wait and see policies, the following is recommended: registration of all implanted valves, follow‐up of a large cohort of valve carriers, comparison of wear test results of preimplant and postretrieval valves, maintenance of a reference stock of valves and materials, and submission of failure scenarios to certifying bodies.
Daily Versus Standard Hemodialysis: One Year Experience
Authors: Traeger J. , Sibai‐Galland R. , Delawari E. , Arkouche W.
Published: March 2003

Abstract: The aim of this study was to compare clinical and biological results in 4 standard hemodialyzed patients originally treated by three 4–5 h sessions per week and converted within one year to daily hemodialysis sessions of 2–2.5 h each 6 times per week. The modalities and the total weekly dialysis times remained the same. With daily hemodialysis, the blood pressure and left ventricular mass index decreased significantly (p < 0.01). A significant decrease in the urea time averaged deviation (TAD) (p < 0.005) and increase in the Kt/V index (p < 0.05) were observed. A gain in dry weight was shown with a rise in caloric intake from 33 ± 3.21 to 40.8 ± 6.35 kcal/kg/day (p < 0.05), and the normalized protein catabolic rate (nPCR) increased significantly (p < 0.0038). One patient who was receiving erythropoietin (EPO) for anemia could stop his treatment. No arteriovenous fistula complications were observed. Daily hemodialysis seems to be the method of choice to manage hypertension and left ventricular hypertrophy in uremic patients. The increase of the urea TAD to a value closer to that of the healthy kidney due to the increase of the frequency of dialysis is probably the main explanation for clinical improvement.
Peritoneal Clearance and Peritoneal Transfer of Oxalic Acid, Vitamin C, and Vitamin B6 During Continuous Ambulatory Peritoneal Dialysis
Authors: Mydlík  , Derzsiová  , Šváč  , Dlhopolček  , Žemberová
Published: March 2003

The peritoneal clearance and peritoneal transfer of oxalic acid, vitamin C, and vitamin B6 in 32 patients during continuous ambulatory peritoneal dialysis (CAPD) using peritoneal dialysis solutions containing 1.5% or 2.5% glucose were examined. The plasma level of oxalic acid was significantly elevated in all patients, plasma vitamin C was in the normal range or in the upper margin of the normal range, and plasma vitamin B6 was in the normal range. The peritoneal clearance of oxalic acid was significantly lower, and the peritoneal clearance of vitamin B6 was the lowest in comparison to the peritoneal clearance of urea. With the exception of vitamin B6, the peritoneal clearance and peritoneal transfer of the examined parameters increased using the dialysis solution containing 2.5% glucose. We found direct relationships between the plasma levels of oxalic acid and creatinine as well as plasma vitamin C and between the peritoneal transfer of oxalic acid and the peritoneal transfer of vitamin C as well as vitamin B6. The significant hyperoxalemia of our patients was found to persist despite the relatively high peritoneal transfer of oxalic acid during CAPD. These results suggest that CAPD is not a method effective enough for permanent reduction of the plasma levels of oxalic acid.
Minimally Invasive Cardiac Surgery in the Adult: Surgical Instruments, Equipment, and Techniques
Authors: Kitamura Masaya , Uwabe Kazuhiko , Hirota Jun , Kawai Akihiko , Endo Masahiro , Koyanagi Hitoshi
Published: March 2003

To clarify the special instruments and equipment used for minimally invasive cardiac surgery (MICS), we examined the initial experiences with MICS operations with ministernotomy or minithoracotomy at our institution. Fifty adult patients with congenital, valvular, and/or ischemic heart diseases underwent MICS operations, and all surgical procedures were completed without conversion to full sternotomy. The length of the skin incision was about 10 cm or less in all patients. Postoperative recovery was favorable, and the majority of the patients were discharged from the hospital around the end of the second postoperative week. In this series of patients, an oscillating bone saw, lifting type retractor, 2 blade spreader, cannula with a balloon, and right‐angled aortic clamp among other items, were very useful for successfully performing various operations with MICS approaches and techniques. The associated results suggest that MICS with ministernotomy or minithoracotomy was feasible using special instruments and equipment and could be encouraged for adult patients with various cardiovascular diseases.
Left Ventricular Mass Regression After Implantation of St. Jude Medical Cardiac Valves in Small Aortic Roots
Authors: Murakami Taiji , Kikugawa Daiki , Endoh Kouichi , Ishida Atsuhisa , Tabuchi Atsushi , Morita Ichiro , Masaki Hisao , Inada Hiroshi , Fujiwara Takashi
Published: March 2003

In this study, we analyzed the extent of regression of left ventricular hypertrophy in patients who received small St. Jude Medical (SJM) aortic valves and compared the results with those of another group receiving larger valves. Eighty‐eight patients received either 19 or 21 mm valves (Group 1, 25 patients) or either 23 or 25 mm valves (Group 2, 53 patients). Echocardiographic studies were done before the operation and 5 years postoperatively. At follow‐up a significant reduction in the left ventricular mass was found for both patient groups (p < 0.0001). Doppler echocardiography derived pressure gradients for both groups were obtained during the follow‐up period. As expected, the patients in Group 1 had higher peak pressure gradients than did those in Group 2. However, there was no significant difference between the 2 groups or any significant correlations between peak pressure gradients and body surface area (BSA). Actuarial survival was 84.7% at 15 years for Group 1 and 85.9% at 17 years for Group 2. Actuarial freedom from valve related events was 91.4 % at 15 years for Group 1 and 82.7% at 17 years for Group 2. There was no significant difference in survival or valve related event free curves between the 2 groups. After implantations of SJM valves in small aortic roots, significant left ventricular mass regression was obtained, and the results were comparable to those for valves of other sizes. The long‐term performance of aortic valve replacement with small valves was satisfactory as judged by improvement in the functional class of patients and survival statistics, the durability of the prosthesis, and valve related morbidity comparable to that of valves of other sizes.
Ex Vivo Liver Perfusion with Arterial Blood from A Pig with Ischemic Liver Failure
Authors: Nakamura Noboru , Kamiyama Yasuo , Takai Soichiro , Kamiya Tomoo , Imamura Atsushi , Matsui Yoichi , Wei Tu , Kaibori Masaki , Satoi Sohei , Saitoh Takamichi , Yoshida Hideyuki , Yoshida Kazumasa , Kwon A‐Hon
Published: March 2003

To simplify liver support using an ex vivo perfused liver, an isolated pig liver was perfused with arterial blood from the recipient pig while monitoring the metabolic capacity of the ex vivo perfused liver. It was possible to perfuse the isolated liver for more than 24 h using arterial blood from a pig with ischemic liver failure. The viability of the isolated liver during support from the liver failure pig was well maintained as evidenced by the high adenylate energy charge (0.815) and a constant ketone body ratio (KBR) of over 1.0 sampled from the hepatic vein. Oxygen consumption (mean, 29.0 μl/min/g of liver) and bile production (mean, 24.2 μl/h/g of liver) were significantly higher in the isolated liver connected to the liver failure pig than in the organ connected to the pig without liver failure (15.5 μl/min/g and 7.3 μl/h/g, respectively). These findings suggest that this liver support system has sufficient metabolic capacity to support a failed liver. Further studies may provide the experimental basis necessary for the clinical application of this device in treatment of patients with acute liver failure.
Prevalence of Latex Sensitivity Among Patients with Chronic Renal Failure: A New Risk Group?
Authors: Kalpakliogˇlu Ayşe Füsun , Aydin
Published: March 2003

Latex has been documented as causing immediate hypersensitivity reactions in forms ranging from contact urticaria to severe anaphylaxis. The prevalence of latex allergy appears to be higher in certain risk groups as a result of increased exposure or an increased intrinsic predilection for atopy. The purpose of the present study was to assess latex sensitivity in a large group of patients who are undergoing regular dialysis because of chronic renal failure (CRF) and to evaluate the relationship between latex sensitivity and skin prick test (SPT) responses to fruit allergens. Of the 268 patients tested, 3 subjects (1.1%) were found to have latex sensitivity via SPT. Although atopy was not demonstrated in any SPT positive subjects, there appears to be a considerable degree of crossreactivity between latex and certain fruit allergens which can be suggested as one subtext in the SPT positive patients. In conclusion, CRF patients with no history of hypersensitivity reactions should not be considered at risk for developing latex sensitization despite their frequent exposure.
The Removal of Beta‐2‐microglobulin by an Immunoadsorption Wall
Authors: Yang Tsung Hua , Lee Chau Jen , Chu I Ming , Hwang Jyh Chang , Yang Tsung Lin
Published: March 2003

The accumulation of beta‐2‐microglobulin (β2M) in collagen‐rich tissues has been proven to be the main cause of dialysis related amyloidosis. However, it remains uncertain which technique for the removal of β2M can be used without compromising the advantages of other dialysis strategies. A new concept, an immunoadsorption wall, which combines the principles of immunoisolation and immunoadsorption is proposed to remove β2M. The present investigations suggested that the application of the concept to clinical use is feasible and worthwhile. The concept, if validated, will help shape a novel multitask type of artificial kidney based on the combination of different separation technologies.
The Anemia in Continuous Ambulatory Peritoneal Dialysis Patients Is Related to Kt/V Index
Authors: Opatrný Jr. Karel , Opatrná Sylvie , Šefrna František , Wirth Jan
Published: March 2003

Anemia in chronic renal failure causes a number of serious problems to the patient. As a result, it is imperative to make use of all rational options to alleviate it. The present study addresses the question, the answer to which is not yet known, whether or not the degree of anemia depends on the efficacy of continuous ambulatory peritoneal dialysis (CAPD) and, if so, what the importance of peritoneal clearance and residual renal function is. A significant correlation between the hematocrit (Hct) and the total weekly Kt/V index (tKt/V) (r = 0.61, p < 0.01), total weekly creatinine clearance (tCLCR) (r = 0.50, p < 0.05), and residual glomerular filtration rate (r = 0.43, p < 0.05) was demonstrated in a group of 22 CAPD patients. Stepwise regression analysis showed that of all the variables monitored, Hct depends exclusively on tKt/V (p < 0.01, r2 = 0.37). The value of Hct in a group of patients with a tKt/V < 2.3 (n = 15) was 28.9 ± 1.2% (arithmetic mean ± SEM) while in a group with a tKt/V ≥ 2.3 (n = 7), it was 35.1 ± 1.9% (p < 0.01). On dividing tKt/V and tCLCR into their peritoneal and renal components, a significant correlation between Hct and renal Kt/V (r = 0.47, p < 0.05) was found; stepwise regression analysis identified renal Kt/V (p < 0.01) and peritoneal Kt/V (p < 0.05), with R2 = 0.38 as major variables with an effect on Hct. The authors conclude the efficacy of blood purification is another factor affecting renal anemia in CAPD patients. The relationship between anemia and blood purification is best expressed using the Kt/V index. The Kt/V provided by one's own kidneys seems to be of greater importance for anemia than the Kt/V provided by peritoneal dialysis. The results provide the basis for prospective interventional studies.
Cellulose Carbamates and Derivatives as Hemocompatible Membrane Materials for Hemodialysis
Authors: Diamantoglou  , Platz  , Vienken
Published: March 2003

Dialysis membranes made from regenerated cellulose are under dispute because of their alleged lack of hemocompatibility. The introduction of membranes from synthetically modified cellulose, like cellulose acetate or Hemophan, has proven, however, that hemocompatible membranes can be fabricated from cellulose by means of chemical surface modifications. In addition to membranes made from modified cellulose like ethers or esters, which were investigated in earlier experiments, we looked for further cellulose modifications to be assessed for their hemocompatibility. For this purpose, we synthesized a series of cellulose carbamate derivatives to profit from the excellent hemocompatibility pattern of the urethane family. In vitro investigations on membranes made from these cellulose modifications proved a direct relationship between the degree of modification and hemocompatibility. This was proven for the following 3 representative hemocompatibility parameters: complement C5a generation, thrombin‐antithrombin (TAT) III formation, and platelet count (PC). As already shown for modifications made from cellulose esters, a direct dependency between improved hemocompatibility and the degree of substitution (DS) in the cellulose molecule could be found. In our experiments, a degree of substitution below a value of 0.1 led to a nearly complete suppression of complement activation for all cellulose carbamates under investigation. In contrast to data on cellulose esters, we observed that molecular weight or molecular conformation of chemical substituents exerted only a minor effect on the hemocompatibility pattern. In addition, data on cellulose carbamate esters (e.g., cellulose succinate‐phenyl‐carbamate) show that a simultaneous but balanced substitution with hydrophilic and hydrophobic groups at the surface of the cellulose polymer is a further prerequisite for optimal hemocompatibility. It seems that the carbamate configuration per se has a positive effect on the hemocompatibility pattern of synthetically modified cellulose membranes.
In Vitro Comparison Study of CD63 and CD62P Expression After Contacting Leukocyte Filters
Authors: Fukunaga Ken , Shimoyama Takashi , Yamaji Ken , Yamane Shingo , Sueoka Akinori , Nosé Yukihiko
Published: March 2003

CD63 and CD62P have been recognized as platelet activation markers. This study investigated the secretion of these antigens to compare the platelet activation between a newly developed stainless steel leukocyte filter (SSLF) and 7 polyester or polyurethane commercially available leukocyte filters. Flow cytometry demonstrated that the SSLF initiated significantly smaller effects in terms of mean fluorescence intensity of CD63 (p < 0.03) and of the amount of CD62P expressing platelets (p < 0.002) compared to the polyurethane filters. However, there was no statistical difference between the SSLF and polyester filters. The result of this study suggests that the SSLF caused less platelet activation than the polyurethane filters and has biocompatible characteristics comparable to the currently available polyester filters. Stainless steel was selected because of its physicochemical conductivity. With these results, further evaluation of the SSLF will be continued in an attempt to develop an active immunomodulator using this unique characteristic.
Platelet‐Leukocyte Aggregates During Hemodialysis: Effect of Membrane Type
Authors: Gawaz Meinrad P. , Mujais Salim K. , Schmidt Bärbel , Blumenstein Mathias , Gurland Hans J.
Published: March 2003

Hemodialysis is associated with the formation of platelet‐leukocyte aggregates. Whether this phenomenon is hemodialysis (HD) membrane dependent is unclear. To evaluate this process, we examined respectively platelet activation (anti‐CD41, anti‐CD62, and antifibrinogen monoclonal antibodies [MoAb] binding), leukocyte activation (CD11b expression), and the appearance of platelet specific antigens on leukocytes as an index of platelet‐leukocyte aggregation during HD using 3 different membrane materials, Cuprophan, Hemophan, and polysulfone. Flow cytometric techniques and specific MoAb were used. All parameters were assayed 5 min after initiation of HD to avoid the confounding variable of leukopenia and resultant cell subpopulation analysis. Platelet activation (anti‐CD62 and antifibrinogen binding) occurred only with Cuprophan. All 3 membranes induced equivalent increases in CD11b expression on neutrophils and similarly increased the binding of anti‐CD41 to neutrophils, reflecting an increment in the formation of platelet neutrophil aggregates. However, only Cuprophan induced an increase in anti‐CD62 binding to neutrophils, suggesting that the aggregated platelets linked to neutrophils were activated. Increased anti‐CD41 binding by monocytes was similarly observed with all 3 membranes. However, only polysulfone induced an increase in CD11b expression and fibrinogen binding to monocytes. We conclude that while the formation of platelet leukocyte aggregates appears to be a universal phenomenon in HD occurring with a variety of membrane types, subtypes of this phenomenon consisting of activated platelets and fibrinogen binding may be membrane dependent. This phenomenon may serve as a new biocompatibility parameter and may shed light on some of the biologic consequences of hemodialysis.
The Development of a Control Method for a Total Artificial Heart Using Mixed Venous Oxygen Saturation
Authors: Nakamura Makoto , Masuzawa Toru , Tatsumi Eisuke , Taenaka Yoshiyuki , Nakamura Tomomichi , Zhang Bin , Nakatani Takeshi , Takano Hisateru , Ohno Takashi
Published: March 2003

For physiological control of a total artificial heart (TAH), applying mixed venous oxygen saturation (Sv o2) as a parameter for TAH control is a promising approach regarding sensitivity to the recipient's oxygen demand and the practical possibility of continuous monitoring using near infrared rays through transparent blood pump housings. To develop a control method for the TAH using Sv
o2, the relationship between Sv
o2 and cardiac output (CO) was investigated in a normal calf, and a control algorithm was developed based on this correlation. Then the feasibility of this method (Sv
o2 mode) was evaluated in a calf implanted with a pneumatic TAH and compared with the fixed drive control mode (fixed mode) in which the drive parameters were unchanged. The calf performed a graded exercise test in both modes. The CO was effectively increased from 7.3 to 13.0 L/min in the Sv
o2 mode, and the capacity for exercise was augmented compared to the fixed mode. We conclude that this Sv
o2 mode is feasible and may be effectively applied in TAH control.
Permanent Cardiac Assistance from Skeletal Muscle: A Prospect for the New Millennium
Authors: Salmons Stanley
Published: March 2003

This paper looks at the prospects for new surgical solutions to the problem of end‐stage heart failure based on cardiac assistance from skeletal muscle. The current status of the main biological approaches, cardiomyoplasty, aortomyoplasty, and the skeletal muscle ventricle, are discussed, followed by a consideration of some of the important basic issues that need to be addressed if these techniques are to achieve their full potential. Although there is a review element to the paper, the main emphasis is on the work of our own research group and collaborating workers.
A Custom Designed Chip to Control an Implantable Stimulator and Telemetry System for Control of Paralyzed Muscles
Authors: Pourmehdi Soheyl , Strojnik Primoz , Peckham Hunter , Buckett James , Smith Brian
Published: March 2003

A custom designed chip has been developed for the control of paralyzed muscles. The system is capable of fulfilling the stimulus and telemetry needs of advanced functional neuromuscular stimulation (FNS) applications requiring multiple channels of stimulation and multiple channels for sensor or biopotential sensing. An inductive radiofrequency link provides power to the implant device as well as 2 way transcutaneous communication. An application specific integrated circuit (ASIC) decodes the commands and provides functional control within the implant, and modular circuitry provides specific implant functions. The ASIC chip provides up to 32 independent channels of stimulation with independent control of stimulus pulse duration, pulse amplitude, interphase delay, recharge phase duration, and pulse interval. It can also control up to 8 independent back telemetry analog channels with independent control of sampling rate and pulse powering parameters (amplitude and duration). The mixed analog digital chip has been fabricated in 1.2 μm n‐well CMOS technology.
Demand for and Use of Functional Electrical Stimulation Systems and Conventional Orthoses in the Spinal Lesioned Community of the UK
Authors: Maxwell Douglas J. , Granat Malcolm H. , Baardman Gert , Hermens Hermie J.
Published: March 2003

The use of and demand for functional electrical stimulation (FES) systems and conventional orthoses in the spinal cord lesioned population was assessed. The assessment was conducted by a postal survey of the members of the spinal injury associations in the U.K. Out of all the respondents, only 2% had used an FES system for walking. In comparison, 13% had used some kind of orthosis. Of the small numbers who had used an FES system for walking, more than half had no functional walking abilities. The majority of orthosis users had some independent walking ability. The demand for walking improvements was high among the respondents although this was not matched by the demand for improved orthotic solutions. In conclusion, it would appear that there is a need for simple FES systems offering walking improvement to the incomplete spinal cord lesioned (SCI) subject.
Functional Control of the Hand in Tetraplegics Based on Residual Synergistic EMG Activity
Authors: Thorsen Rune , Ferrarin Maurizio , Spadone Raffaella , Frigo Carlo
Published: March 2003

A microprocessor controlled device (MeCFES) was used for the investigation of the possibility of restoring hand function in C5 tetraplegics with paralysis of the hand. To date, 3 tetraplegics have been testing the system. The myoelectric signals from wrist extension were recorded and used as control signals for functional electrical stimulation (FES) of thumb adduction/flexion. The results have shown that the device can improve the hand function of tetraplegics. In this part of the work, a hand function test was designed and used to assess the results.
Three‐Dimensional Changes in the Upper Airway During Neuromuscular Stimulation of Laryngeal Muscles
Authors: Ludlow Christy L. , Hang Cynthia , Bielamowicz Steven , Choyke Peter , Hampshire Victoria , Selbie W. Scott
Published: March 2003

During swallowing, airway protection depends upon adequate glottal closure and laryngeal elevation to prevent the entry of substances into the airway. Three‐dimensional changes in the upper airway during laryngeal muscle stimulation in a canine model were quantified in animals implanted with Peterson type stimulating electrodes in the inferior and superior portions of the thyroarytenoid muscle, together with a reference electrode. Computer tomography scanning was performed on an IMATRON scanner with a 3 mm slice thickness advanced at overlapping 1 mm increments. Stimulation of the thyroarytenoid muscle produced adductions of the vocal fold towards the midline and changes in the supraglottic region as well as the glottis; the glottic wall was compressed medially above and below the glottis. These results suggest that chronic neuromuscular stimulation can effect glottic protection by reducing the glottal opening and may be beneficial for patients with central control disorders affecting airway protection during swallowing.
Dynamic Force Responses in Electrically Stimulated Triceps Surae Muscles: Effects of Fatigue and Temperature
Authors: Rafolt Dietmar , Gallasch Eugen , Mayr Winfried , Lanmüller Hermann
Published: March 2003

To elicit dynamic force responses (unfused tetani) in isometric triceps surae muscles, low frequency electrical stimulation ranging from 12.5 to 30.0 Hz was applied. The fusing frequency (FF) and the relative dynamic force amplitude (DF) at the 20% and 40% maximum voluntary contraction (MVC) levels were calculated as parameters to determine effects of muscle fatigue (n = 6) and local muscle cooling. In the fatigued muscle (15 min plantar flexion at a 20% MVC level), the FF and DF increased when the fatigue was induced by voluntary contraction (FF increased from 19.6 to 22.5 Hz at 20% MVC) and also when induced by electrical stimulation (FF increased from 19.2 to 23.3 Hz). Cooling of the muscles showed an inverse effect on both parameters, indicating contractile slowing. The responsible physiological mechanisms as well as practical applications, using low frequency stimulation to monitor degenerative changes in muscles, are discussed.
Development of an Ultracompact Integrated Heart‐Lung Assist Device
Authors: Tatsumi Eisuke , Takano Hisateru , Taenaka Yoshiyuki , Nishimura Takashi , Kakuta Yukihide , Nakata Masako , Tsukiya Tomonori , Nishinaka Tomohiro
Published: March 2003

A novel integrated heart‐lung assist device has been developed as a simple to use portable cardiopulmonary support system. The device comprises a centrifugal pump and an artificial lung, which is located around the pump, in an all in one system. The special membrane employed precludes plasma breakthrough in protracted use and enables preprimed setup. Test lungs consisting of the same membrane preserved gas exchange function well after 3 months of preprimed storage. The entire blood contacting surface is treated with covalent heparin bonding to impart good antithrombogenicity. Heparin bonded test lungs could be continuously perfused without systemic anticoagulation as long as 36 days in a venoarterial bypass chronic animal study using goats. The prototype device (diameter, 126 mm; height, 59 mm; membrane area, 0.85 m2; priming volume, 180 ml) demonstrated 9 L/min pump output at a 400 mm Hg pressure head and 180 ml/min oxygen and 110 ml/min carbon dioxide transfer rates at 5 L/min blood flow. We conclude that this device has potential to be the next generation cardiopulmonary support system.
Test Controller Design, Implementation, and Performance for a Magnetic Suspension Continuous Flow Ventricular Assist Device
Authors: Hilton Edgar F. , Allaire Paul E. , Wei Naihong , Baloh Michael J. , Bearnson Gill , Olsen Don B. , Khanwilkar Pratap
Published: March 2003

A new continuous flow ventricular assist device using full magnetic suspension has been designed, constructed, and tested. The magnetic suspension centers the centrifugal pump impeller within the clearance passages in the pump, thus avoiding any form of contact. The noncontact operation is designed to give very high expected mechanical reliability, large clearances, low hemolysis, and a relatively small size compared to current pulsatile devices. A unique configuration of magnetic actuators on the inlet side and exit sides of the impeller provides full 5 axis control and suspension of the impeller. The bearing system is divided into segments which allow for 3 displacement axes and 2 angular control axes. The controller chosen for the first suspension tests consists of a decentralized set of 5 proportional integral derivative (PID) controllers. This document describes both the controller and an overview of some results pertaining to the magnetic bearing performance. The pump has been successfully operated in both water and blood under design conditions suitable for use as a ventricular assist device.
Extracorporeal Membrane Oxygenation for Perioperative Support in Neonatal and Pediatric Cardiac Transplantation
Authors: Hopper Andrew O. , Pageau Janie , Job Leela , Heart Joya , Deming Douglas D. , Peverini Ricardo L.
Published: March 2003

Abstract: Currently there is a lack of consensus on guidelines in the clinical application of extracorporeal membrane oxygenation (ECMO) in neonatal and pediatric cardiac transplantation patients. In this context, given the limited data presently available through the Extracorporeal Life Support Organization (ELSO) Registry, we conducted a preliminary survey to specifically evaluate the practice of using ECMO as a bridge to cardiac transplantation or as posttransplantation therapy for failure to wean from cardiopulmonary bypass or graft failure. We received responses to our questionnaire from 95 of 118 (81%) centers located in the U.S.A. and abroad. Of the 95 centers that responded, 36 were performing neonatal/pediatric cardiac transplants, with 29 centers reporting the concomitant use of ECMO to support cardiac transplant patients. There was wide variability in the responses from the 29 centers to a selected list of relative ECMO contraindications. However, only 7 centers had specific ECMO entry criteria for cardiac transplant patients. Fifteen of the 29 centers provided relevant data on cardiac transplant patients including the proportions of neonatal (11 of 37) and pediatric (63 of 217) patients requiring ECMO; neonatal (2 of 5) and pediatric (16 of 27) patients surviving to transplant; and neonatal (1 of 5) and pediatric (12 of 27) patients surviving to hospital discharge. These findings confirm the important role of ECMO in providing perioperative support in neonatal and pediatric cardiac transplantation patients. However, the lack of consensus among centers contributes to uncertainty in the decision making process to offer ECMO and to utilize ECMO effectively in this high risk population. We recommend that institution‐specific information be collected, either using the ELSO Registry (or by a similar multicentric database) to develop specific guidelines for ECMO applications in cardiac transplant patients, and to carefully monitor and follow up EMCO treated patients to further evaluate the efficacy of this limited resource.
Natural Changes in Peritoneal Equilibration Test Results in Continuous Ambulatory Peritoneal Dialysis Patients: A Retrospective, Seven Year Cohort Survey
Authors: Hung Kuan‐Yu , Huang Jenq‐Wen , Tsai Tun‐Jun , Chen Wan‐Yu
Published: March 2003

Abstract: We conducted a retrospective, 7 year cohort survey to examine the natural changes in peritoneal equilibration test (PET) results in patients with long‐term uneventful continuous ambulatory peritoneal dialysis (CAPD). Thirty‐two (17 males, 15 females) patients on CAPD with two or more standard PETs performed more than 6 months apart, in the absence of peritoneal insult, were included. Changes and pattern of PET results were evaluated by the dialysate to plasma ratio of creatinine (D:P‐cre), the fourth h dialysate to instilled glucose ratio (D4:Do) and ultrafiltration volume (UF, ml). The subgroups included high (H), high‐average (HA), low‐average (LA), or low (L) transporters with the dividing ratios (D:P‐cre) of >0.81, >0.65 to 0.81, >0.5 to 0.65, and <0.5, respectively. The median D:P‐cre significantly decreased (p = 0.04), but neither the D4:Do nor the final median UF significantly decreased. The change in D:P‐cre was strongly and inversely correlated with the initial D:P‐cre value (r = −0.68; p < 0.05). A similar relationship was found between the change in the final D4:Do and the initial D4:Do (r = −0.752; p < 0.01) and between the change in the final UF and the initial UF (r = −0.875; p < 0.01). No correlation was found between the change in D:P‐cre and the age of the patient, the time interval between PETs, monthly dialysate glucose exposure, or underlying diabetes/non‐diabetes. The final peritoneal transport pattern was altered with 5 (15.6%) patients remaining in the extreme subgroups (H or L) and, by contrast, 84.4% (27/32) of the patients now in the averaged (HA or LA) groups (p < 0.01, χ2 test). We demonstrated a natural “centralization” migration of PET results after long‐term uneventful CAPD, which may help to explain why patients with extreme PET characteristics, that is, H or L, continued to do well on CAPD.
Design and Test of a Vascular Access Device
Authors: Verkerke Gijsbertus Jacob , Rakhorst Gerhard
Published: March 2003

Abstract: Transarterial left ventricular assist devices (LVADs), such as the Hemopump, IABP, and PUCA‐pump, are meant to be introduced into the body via the femoral or axillary artery without major surgery. For certain applications, introduction is performed directly into the aorta via an open thorax procedure. A prototype of a vascular access device has been realized that allows direct access into the aorta as an alternative for the common surgical graft anastomosis suturing technique. The device consists of a metal tube acting as a circular knife to cut a hole in the aortic wall, a screw to store the removed part of the aortic wall, and a plastic tube that is introduced through the hole and tightly connected to the aortic wall. The device could be placed without aortic clamping. The device has been tested on a slaughterhouse porcine aorta. A low‐pressurized aorta appeared to be the worst case; thus, two animal experiments in the low‐pressurized pulmonary artery were performed. No leakage occurred for pressures between 40 and 300 mm Hg.
Diameter of Inferior Caval Vein and Impedance Analysis for Assessment of Hydration Status in Peritoneal Dialysis
Authors: Oe Barry , De Fijter Carola W.H. , Geers Tom B.M. , Vos Pieter F. , Donker Ab J.M. , De Vries Peter M.J.M.
Published: March 2003

Abstract: In 19 stable peritoneal dialysis (PD) patients, hydration status was evaluated by measurement of vena cava diameter (VCD) and bioelectrical impedance analysis (BIA) variables: intracellular water (ICW), extracellular water (ECW), and total body water (TBW). We investigated whether BIA can replace VCD. VCD did not correlate with TBW but correlated moderately with ECW/TBW (r = 0.42; 0.025 < p < 0.05) and ICW/ECW (r = −0.47; p < 0.025). Patients with underhydration (n = 4; VCD <8 mm/m2) revealed limits for BIA variables as ICW/ECW (>1.50) and ECW/TBW (<0.40). The same held true for overhydration (n = 5; VCD >11.5 mm/m2): ICW/ECW (<1.50) and ECW/TBW (>0.40). Although the positive predictive value of ICW/ECW and ECW/TBW for both under‐ and overhydration was only 50% and 54%, respectively, there were no false negative values. Although BIA cannot replace VCD in PD patients, the reverse holds true as well. Combining BIA and VCD may lead to a better estimation of hydration status because both techniques provide complementary information.
Flow Characteristics Past Jellyfish and St. Vincent Valves in the Aortic Position Under Physiological Pulsatile Flow Conditions
Authors: Morsi Yos S. , Sakhaeimanesh Ali A.
Published: March 2003

Abstract: Thrombus formation and hemolysis have been linked to the dynamic flow characteristics of heart valve prostheses. To enhance our understanding of the flow characteristics past the aortic position of a Jellyfish (JF) valve in the left ventricle, in vitro laser Doppler anemometry (LDA) measurements were carried out under physiological pulsatile flow conditions. The hemodynamic performance of the JF valve was then compared with that of the St. Vincent (SV) valve. The comparison was given in terms of mean systolic pressure drop, back flow energy losses, flow velocity, and shear stresses at various locations downstream of both valves and at cardiac outputs of 3.5 L/min, 4.5 L/min, and 6.5 L/min respectively. The results indicated that both valves created disturbed flow fields with elevated levels of turbulent shear stress as well as higher levels of turbulence in the immediate vicinity of the valve and up to 1 diameter of the pipe (D) downstream of the valve. At a location further downstream, the JF valve showed better flow characteristics than the SV in terms of velocity profiles and turbulent shear stresses. The closure volume of the SV valve was found to be 2.5 times higher than that of the JF valve. Moreover, the total back flow losses and mean systolic pressure drop also were found to be higher in the SV than the JF valve.