bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Hox cluster from the mosquito Anopheles gambiae (Diptera: culicidae)
Authors: Powers Thomas P. , Hogan Jim , Ke Zhaoxi , Dymbrowski Kirk , Wang Xuelan , Collins Frank H. , Kaufman Thomas C.
Published: March 2003

SUMMARY The Hox genes have been found to encode transcription factors, which specify the morphological identity of structures along the anteroposterior axis of animals ranging from worms to mice. The canonical set of nine genes is organized in a cluster in the genome of several protostomes and deuterostomes. However, within insects, whereas the Hox genes are organized in a single cluster in the beetle Tribolium castaneum, they are split into two separate groups in the flies Drosophila melanogaster and Drosophila virilis. The significance of a split Hox cluster is unknown and has been observed in only one organism outside the Drosophila lineage: the nematode Caenorhabditis elegans. We have cloned a majority of the Hox genes from the mosquito Anopheles gambiae (Diptera: Culicidae) and compared their genomic organization with that of Tribolium and Drosophila to determine if a split Hox cluster is found in dipterans aside from the Drosophilidae. We find that the Hox genes in Anopheles, as in Tribolium, are organized in a single cluster that spans a genomic region of at least 700 kb. This finding suggests that, within the insect genome, the partition of the Hox cluster may have evolved exclusively within the Drosophila lineage. The genomic structures of the resident genes, however, appear to be largely conserved between A. gambiae and D. melanogaster.
Microevolutionary analysis of the nematode genus Pristionchus suggests a recent evolution of redundant developmental mechanisms during vulva formation
Authors: Srinivasan Jagan , Pires‐daSilva André , Gutierrez Arturo , Zheng Min , Jungblut Benno , Witte Hanh , Schlak Isabel , Sommer Ralf J.
Published: March 2003

SUMMARY To identify the mechanisms by which molecular variation is introduced into developmental systems, microevolutionary approaches to evolutionary developmental biology have to be taken. Here, we describe the molecular and developmental characterization of laboratory strains of the nematode genus Pristionchus, which lays a foundation for a microevolutionary analysis of vulva development. We describe 13 laboratory strains of the Pristionchus genus that are derived from natural isolates from around the world. Mating experiments and ITS sequence analysis indicated that these 13 strains represent four different species: the gonochoristic species P. lheritieri and three hermaphroditic species, P. pacificus, P. maupasi, and an as yet undescribed species Pristionchus sp., respectively. P. pacificus is represented by five different strains isolated from California, Washington, Hawaii, Ontario, and Poland. Developmental differences during vulva formation are observed between strains from different species but also between strains of P. pacificus, like the strains from California and Poland. In particular, redundant developmental mechanisms present during vulva formation in P. pacificus var. California are absent in other strains. Amplified restriction fragment length polymorphism (AFLP) analyses of the P. pacificus strains revealed that the American strains are highly polymorphic. In contrast, the developmentally distinct strain from Poland is identical to the Californian strain, suggesting that the developmental differences rely on a small number of changes in developmental control genes rather than the accumulation of changes at multiple loci.
Growth negatively impacts the life span of mammals
Authors: Rollo C. David
Published: March 2003

SUMMARY A negative intraspecific relationship between growth and longevity was proposed in the early 20th century. Indeed, stunting the growth of rodents by restricting their food dramatically extended life span. Subsequently, however, the hypothesis that growth exacerbates aging rates fell into disfavor. Contributing to this was (a) the establishment of a positive relationship between body size and longevity interspecifically, (b) purported antiaging impacts of growth hormone, and (c) the fact that the longevity of even mature rodents that had completed growth was extended by dietary restriction. Furthermore, intraspecific analytical studies failed to provide any clear resolution. This article presents the first global analyses of maximal longevity versus maximum mature mass for laboratory rats and mice, based on a relatively comprehensive compilation of research across the 20th century. Peak body mass (which reflects juvenile growth rates) was negatively associated with longevity within both species. Proximal mechanisms for impacts of growth on longevity appear congruent with the free radical and immunological theories of aging.
Ancient ontogenies: larval development of the Lower Cretaceous anuran Shomronella jordanica (Amphibia: Pipoidea)
Authors: Chipman Ariel D. , Tchernov Eitan
Published: March 2003

SUMMARY The Lower Cretaceous anuran Shomronella jordanica (Pipoidea) is represented by an assemblage of nearly 300 tadpoles of different ages. The size of the assemblage allows a reconstruction of the larval ontogeny of this species. We describe the ossification sequence and growth rates of S. jordanica and present reconstructions of tadpoles at different stages. The ontogeny of the species seems to be similar to that of extant pipids in many aspects. Larvae are similar in shape and size to those of Xenopus laevis but lack the anterior barbels that are typical for all extant pipids. The ossification sequence is closer to that of pipids than to that of other anurans. We present evidence that suggests that this species was terrestrial as an adult, and we discuss the implications of these data for the evolution of anuran development.
Analyzing evolutionary patterns in amniote embryonic development*
Authors: Jeffery Jonathan E. , Bininda‐Emonds Olaf R. P. , Coates Michael I. , Richardson Michael K.
Published: March 2003

SUMMARYHeterochrony (differences in developmental timing between species) is a major mechanism of evolutionary change. However, the dynamic nature of development and the lack of a universal time frame makes heterochrony difficult to analyze. This has important repercussions in any developmental study that compares patterns of morphogenesis and gene expression across species. We describe a method that makes it possible to quantify timing shifts in embryonic development and to map their evolutionary history. By removing a direct dependence on traditional staging series, through the use of a relative time frame, it allows the analysis of developmental sequences across species boundaries. Applying our method to published data on vertebrate development, we identified clear patterns of heterochrony. For example, an early onset of various heart characters occurs throughout amniote evolution. This suggests that advanced (precocious) heart development arose in evolutionary history before endothermy. Our approach can be adapted to analyze other forms of comparative dynamic data, including patterns of developmental gene expression.
A lophotrochozoan twist gene is expressed in the ectomesoderm of the gastropod mollusk Patella vulgata
Authors: Nederbragt Alexander J. , Lespinet Olivier , Van Wageningen Sake , Van Loon André E. , Adoutte André , Dictus Wim J. A. G.
Published: March 2003

SUMMARY The twist gene is known to be involved in mesoderm formation in two of the three clades of bilaterally symmetrical animals: viz. deuterostomes (such as vertebrates) and ecdysozoans (such as arthropods and nematodes). There are currently no data on the spatiotemporal expression of this gene in the third clade, the lophotrochozoans (such as mollusks and annelids). To approach the question of mesoderm homology across bilaterians, we decided to analyze orthologs of this gene in the gastropod mollusk Patella vulgata that belongs to the lophotrochozoans. We present here the cloning, characterization, and phylogenetic analysis of a Patella twist ortholog, Pv‐twi, and determine the early spatiotemporal expression pattern of this gene. Pv‐twi expression was found in the trochophore larva in a subset of the ectomesoderm, one of the two sources of mesoderm in Patella. These data support the idea that twist genes were ancestrally involved in mesoderm differentiation. The absence of Pv‐twi in the second mesodermal source, the endomesoderm, suggests that also other genes must be involved in lophotrochozoan mesoderm differentiation. It therefore remains a question if the mesoderm of all bilaterians is homologous.
Coincident iterated gene expression in the amphioxus neural tube
Authors: Jackman William R. , Kimmel Charles B.
Published: March 2003

SUMMARYThe segmental patterning of the vertebrate hindbrain has been intensely investigated, yet the evolutionary origin of hindbrain segmentation remains unclear. In the vertebrate sister group, amphioxus (Cephalochordata), the embryonic neural tube lacks obvious morphological segmentation, but comparativeHoxgene expression analysis has suggested the presence of a region homologous to the vertebrate hindbrain. Does this region contain ancient segmental features shared with the vertebrate hindbrain? To help address this question we cloned thepaired‐like amphioxus homeodomain geneshoxand found that its expression is segmental in the amphioxus neural tube. We also uncovered a previously uncharacterized iterated neural tube expression pattern of the zinc‐finger geneAmphiKrox.We propose that these genes, along with amphioxusisletandAmphiMnx, share a one‐somite width periodicity of expression in the neural tube, the coincidence of which may reflect an underlying segmental organization. We hypothesize that the segmental patterning of neurons in the neural tube was present in the amphioxus/vertebrate ancestor, but the establishment of a bona fide segmented hindbrain may indeed have arisen in the vertebrate lineage.
Time, pattern, and heterochrony: a study of hyperphalangy in the dolphin embryo flipper
Authors: Richardson Michael K. , Oelschläger Helmut H. A.
Published: March 2003

SUMMARY The forelimb of whales and dolphins is a flipper that shows hyperphalangy (numerous finger bones). Hyperphalangy is also present in marine reptiles, including ichthyosaurs and plesiosaurs. The developmental basis of hyper‐phalangy is unclear. Kükenthal suggested that phalanx anlagen split into three pieces during cetacean development, thereby multiplying the ancestral number. Alternatively, Holder suggested that apical ectodermal ridge (AER)‐directed limb outgrowth might be prolonged by a timing shift (heterochrony), leading to terminal addition of extra phalanges. We prepared a series of whole mounted and serially sectioned embryonic flipper buds of the spotted dolphin Stenella attenuata. This cetacean shows marked hyperphalangy on digits II and III. We confirm previous reports that the proximodistal laying down of phalanges is prolonged in digits II and III. Histology showed that the apical ectoderm was thickened into a cap. There was a weak ridge‐like structure in some embryos. The cap or ridge formed part of a bud‐like mass that persisted on digits II and III at stages when it had disappeared from other digits. Thus the dolphin differs from other mammals in showing a second period of limb outgrowth during which localized hyperphalangy develops. New phalanges only formed at the tip of the digits. These findings are consistent with a model in which heterochrony leads to the terminal addition of new phalanges. Our results are more easily reconciled with the progress zone model than one in which the AER is involved in the expansion of a prepattern. We suggest that patterning mechanisms with a temporal component (i.e., the “progress zone” mechanism) are potential targets for heterochrony during limb evolution.
HELP Apheresis in the Treatment of Sepsis
Authors: Samtleben  , Bengsch  , Boos  , Seide
Published: March 2003

Heparin induced extracorporeal lipoprotein fibrinogen precipitation (HELP) is an established procedure for removal of low‐density lipoprotein (LDL) cholesterol, lipoprotein (a), and fibrinogen in patients with severe hypercholesterolemia. In vitro studies revealed that HELP also removes endotoxin, tumor necrosis factor α (TNF‐α) and C‐reactive protein (CRP). With the intention to treat, we applied this procedure to 4 patients with severe gram‐negative sepsis with highly elevated endotoxin blood levels. Nine treatments were performed, 6 using the standard HELP precipitating buffer and 3 without addition of heparin to the precipitating buffer. Heparin was omitted from the precipitating buffer to avoid fibrinogen depletion in patients at risk (low fibrinogen, postoperative). The average processed plasma volume was 3,386 ml in the standard and 2,963 ml in the modified treatment. Mean reductions (%) in plasma solute concentrations were (standard/modified procedure) as follows: endotoxin, 50/57; TNF‐α, 25/5; CRP, 49/55; fibrinogen, 49/6; total cholesterol, 38/5; and apolipoprotein B (Apo B), 41/2. Both treatment modalities were equally effective in removing endotoxin and CRP. With the modified precipitation buffer, fibrinogen was not removed. To further simplify the extracorporeal treatment, we have designed a closed‐loop circuit with 2 adsorbers in series, one for removal of TNF‐α (dextran sulfate modified cellulose) and the other for removal of endotoxin (DEAE‐cellulose). In vitro evaluation confirmed very efficient endotoxin and TNF‐α removal from plasma. This system is very simple, operates at physiological pH, and uses adsorbers already in clinical use for other purposes.
Characterization of Abnormalities Responsible for Immediate Rejection of Porcine Aortic Valves for the Manufacture of Bioprostheses
Authors: Marinov Gueorgui Russev , Marois Yves , Maxie Grant , Guidoin Robert
Published: March 2003

Gross observation at the slaughterhouse determines the primary selection of porcine aortic valves for the manufacture of bioprostheses. This step is critical because only valves with significant abnormalities are rejected. The present study validated this selection process by investigating the pathological characteristics of one series of accepted valves and one series of rejected valves. Macroscopy, x‐ray examination, light microscopy, and scanning electron microscopy (SEM) were performed on 5 initially rejected valves, 3 leaflets from 3 other initially rejected valves, and 6 valves that successfully passed this first step in the selection process. Abnormalities were macroscopically visible only on the rejected valves and were described as thick white areas, heavy white striations, thin spots, white plaques, and nodules. Individual variability in the structure of each leaflet was more significant in the rejected valves than in the valves that had passed the first inspection. The leaflets of the rejected valves were also irregularly thick with a lack of consistency in the position and prominence of the different layers. The formation of nodules and the presence of white plaques in the inner fibrosa layer were among the pathological features. The initially accepted valves considered defect free under gross observation continued to display some weaknesses, and not all of the valves selected during the first step of the process were suitable to become bioprostheses. Because the manufacturer carries out further quality control inspections at every step of preparation resulting in additional rejections, it is therefore anticipated that all valves with defects will be rejected. None of the rejected valves were defect free, and rejection was fully justified.
New Technologies for Bioartificial Organs
Authors: Wang
Published: March 2003

Each year several hundred thousand Americans die because of organ failure. Organ transplantations have achieved remarkable success, but the source of human organs is limited. Only a small portion of patients can benefit annually from this method of treatment. Immunoisolated living cells as bioartificial organs can be transplanted into humans without the need for immunosuppression and its accompanying side effects. Immunoisolation allows cells from nonhuman species to be used, thereby overcoming the limited supply of human cells available for encapsulation, and the capsule can serve as an ideal cage to keep animal viruses from contacting the human host. To achieve this promise, we have incorporated the pore size distribution into a new design of capsule for the immunoisolation of living cells. In this model the capsule wall is thicker and the pores are bigger than in the current systems. The larger pores will allow the immune system to enter the membrane, and the smaller pores inside the membrane will act as the traps to prevent or delay most of the immune system from passing all the way through to the inner volume of the capsule where the living cells reside. Limited animal studies have supported the advantages of this new entrapment model over the current model. Systematic studies to determine optimal capsule design for human transplantation are now feasible.
Choice, Isolation, and Preparation of Cells for Bioartificial Vascular Grafts
Authors: Noishiki Yasuharu , Yamane Yoshihisa , Okoshi Takafumi , Tomizawa Yasuko , Satoh Shinichi
Published: March 2003

Preparation of cells and tissues for bioartificial vascular grafts is discussed from the viewpoint of tissue engineering. In general, a neointima is not formed on vascular prostheses except at the anastomotic sites. Graft surfaces do not heal and are covered with fresh thrombi for a long period of time after implantation. The delayed healing is, so to speak, an intractable ulcer of the vascular wall. To overcome this problem, we have developed a tissue fragment transplantation method. We consider that neointima formation of vascular prostheses after implantation is a product of tissue engineering in vivo. Therefore, 3 essential elements for tissue engineering, i.e., cells, extracellular matrices, and cytokines, are required for neointima formation. Synthetic vascular prostheses lack one or more of these elements. In this study we demonstrated a standard healing process of fabric vascular prostheses and an antithrombogenic polymer graft using animal models. Then we showed the tissue fragment transplantation method using venous tissues, adipose tissues, and bone marrow. This method provided the 3 essential elements to the prostheses. To allow these elements to be actively engaged in neointima formation, we treated cells and tissues as clumps without enzymatic digestion. We also took advantage of the in vivo environment. With the results we demonstrate our way of thinking in relation to bioartificial vascular grafts.
A Novel Method to Immobilize Bioactive Substances on Hydrophobic Surfaces Using a Polymerizable Cationic Lipid
Authors: Yamazaki Manabu , Kobayashi Ken‐yu , Nakai Tomoko , Mikami Masato , Yoshioka Hiroshi , Mori Yuichi , Satoh Tadaaki , Kubota Sunao
Published: March 2003

We have successfully developed a novel method to stably immobilize bioactive substances that have anionic groups, such as heparin and succinylated collagen (SC), on hydrophobic surfaces through ionic complexation using a polymerizable cationic lipid, diallyl(dioleyl)ammonium bromide (DADOA). It is composed of a hydrophobic part consisting of long hydrocarbon chains and a hydrophilic head with double bonds which render it polymerizable. Analysis of the modification with DADOA and heparin suggested that the modification formed a thin layer, roughly 60 nm in thickness, as a result of the spontaneous deposition of DADOA and heparin dissolved in water, through the hydrophobic interaction between DADOA and the surface and the ionic complexation between DADOA and heparin. The heparin deposition and its rate of release in plasma were 1.5 μg/cm2 and 0.0017 U/cm 2/min, respectively. Cytotoxicity test results showed that the polymerization of the deposited DADOA rendered the modified surface stable and noncytotoxic. Further, antithrombogenicity and cell attachability test results demonstrated that heparin and SC were effectively immobilized on hydrophobic surfaces through ionic complexation. This method has proved useful for the modification of the hydrophobic surfaces of medical devices because the modification process can be performed under aqueous conditions without the use of organic solvents which induce crazing/cracking of plastic casings.
Anionic Collagen: Polymer Composites with Improved Dielectric and Rheological Properties
Authors: Goissis Gilberto , Piccirili Luciana , Goes Julio Cesar , De Guzzi Plepis Ana Maria , Das‐Gupta Dilip K.
Published: March 2003

This work describes the preparation and characterization of anionic collagen composites with rhamsan and vinylidene fluoride‐trifluorethylene with improved rheological and dielectric properties without loss of collagen secondary structure with an interaction occurring between both macromolecules of the composites. On a comparative basis, the force needed for the extrusion of anionic collagen:rhamsan composites was in the range from 0.088 to 0.080 J compared to that for collagen of 0.189 J. Anionic collagen:vinylidene fluoride‐trifluorethylene composites were characterized, in the case of the 1:1 composite, by a pyroelectric coefficient of 1.89 × 10−4 cm−2 K−1, which was significantly higher than those determined under the same conditions for native anionic collagen and vinylidene fluoride‐trifluorethylene.
Flow Visualization as a Complementary Tool to Hemolysis Testing in the Development of Centrifugal Blood Pumps
Authors: Yamane Takashi , Asztalos Balázs , Nishida Masahiro , Masuzawa Toru , Takiura Koki , Taenaka Yoshiyuki , Konishi Yoshiaki , Miyazoe Yuki , Ito Kazuyuki
Published: March 2003

Abstract With a 250% scaled‐up pump model, high speed video camera, and argon ion laser light sheet, flow patterns related to hemolysis were visualized and analyzed with 4 frame particle tracking software. Different flow patterns and shear distributions were clarified by flow visualization for pumps modified to have different hemolysis levels. A combination of in vitro hemolysis tests, flow visualization, and CFD analysis suggested a close relationship between hemolysis and high shear caused by small impeller/casing gaps. Because arbitrary cross sections can be illuminated by laser light sheet, flow visualization is a useful tool in finding locations related to hemolysis in the design process of rotary blood pumps.
Control of the Pulmonary Arterial Resistance by the Use of the Oscillated Assist Flow
Authors: Yambe Tomoyuki , Izutsu Kenji , Hashimoto Hiroyuki , Yoshizawa Makoto , Tanaka Akira , Abe Ken‐ichi , Fukuju Takeo , Miura Makoto , Tabayashi Kou‐ichi , Takeda Hiroshi , Shizuka Kazuhiko , Sonobe Taro , Naganuma Shigeru , Kobayashi Shin‐ichi , Nanka Shunsuke , Nitta Shin‐ichi
Published: March 2003

Abstract In the clinical application of supporting circulation, the treatment of a patient with pulmonary hypertension is very important. We developed the electromagnetically driven vibrating flow pump (VFP) as a totally implantable type ventricular assist system. The artificial heart driven by electromagnetic forces creates high speed oscillation flow around 10–50 Hz. Assistance by high‐speed oscillation flow has an interesting influence on the cardiovascular system. In this study, we carried out research on the influence such oscillation flow had on the pulmonary arterial vessels, and the supporting flow waveform that controlled pulmonary vascular resistance was considered. Six healthy adult goats of both sexes were used in the experiments. We carried out inhalation anesthesia and performed intubation. The thorax was opened through left fourth rib resection. Right heart bypass was performed from the right atrium to the pulmonary artery. The flow of right heart assistance was maintained within 20–25% of total flow. Our purpose was to add flow of a specific high frequency to the right heart circulation. The hemodynamic parameters were recorded on a magnetic tape data recorder and input into a computer through an A‐D converter. A result identified was that the pulmonary vascular resistance changed according to the alteration of the driving frequency of the VFP even during the same flow assistance. The resistance of the pulmonary arterial vessels became smaller when the driving of the VFP of 30 Hz was added to the right heart circulation. This was significant even when compared with continuous flow right heart assist. The characteristics of impedance appeared to have interesting alterations as well. Control of pulmonary vascular resistance by right heart assistance becomes possible if these results are applied. Accordingly, it may become one of the choices for treatment of a patient with pulmonary hypertension.
A Modified Human Ureter Graft Tanned by a New Crosslinking Agent Polyepoxy Compound for Small Diameter Arterial Substitutions: An Experimental Preliminary Study
Authors: Uematsu Masahisa , Okada Masayoshi
Published: March 2003

The effectiveness of human ureter grafts tanned by polyepoxy compound for small diameter arterial substitution was examined in 8 carotid arteries of rabbits, followed by an observation period of either 1 month (n = 6) or 6 months (n = 2). In this model there was no evidence of rejection, aneurysm formation, or infection. The modified human ureter showed excellent patency in all cases as well as excellent function, and the histological evaluation revealed monolayer endothelial‐like cells covering all of the surface of the graft as was expected. No intimal hyperplasia was demonstrated at either anastomotic site. This study suggests that our newly designed polyepoxy compound fixed human ureter could serve as a satisfactory blood conduit with good long‐term patency for substitution.
Minimally Invasive Pervaginam Procedures for the Treatment of Female Stress Incontinence Using a New Pubic Bone Anchoring System
Authors: Madjar Shahar , Wald Moshe , Halachmi Sarel , Issaq Elias , Moskovitz Boaz , Beyar Mordechai , Nativ Ofer
Published: March 2003

The purpose of this ongoing study is to evaluate the safety and efficacy of new minimally invasive pervaginam cystourethropexy and sling procedures for the treatment of female genuine stress urinary incontinence. A total of 75 women (mean age, 52.8 years) underwent either a cystourethropexy or a sling procedure. A miniature bone anchor and a staple‐like bone anchor driver were used for the fixation of periurethral tissue or a xenogenic sling to the pubic bone. With a mean follow‐up of eight months, 61 patients (82%) were completely cured of stress incontinence, 10 (14%) reported a more than 50% decrease in pad usage, and 4 patients showed failure early following surgery. The exclusively pervaginam cystourethropexy and sling procedures are minimally invasive, safe, and effective. Further experience and longer follow‐up are necessary to establish their role in the treatment of women with stress urinary incontinence.
A Newly Developed On‐line Monitoring System for the Determination of Serum Electrolytes and Urea During Hemodialysis
Authors: Yanai Mitsuru , Kihara Kazuhiko , Yamada Akio , Takahashi Susumu , Sugino Nobuhiro
Published: March 2003

Continuous monitoring of serum solute concentrations throughout a dialysis session could be beneficial for the prevention of intradialytic morbidity such as hypotension and for the confirmation of dialysis adequacy. In this paper, we introduce a new on‐line monitoring system for use during hemodialysis sessions, a system developed for the continuous observation of serum biochemical data. Using this system, we also show the possibility of clinical applications. Intradialytic hypotension could be prevented by the observation of filtrate sodium concentration and the control of dialysate sodium concentration. The termination of a dialysis session could be decided by the observation of the filtrate urea nitrogen, on the basis of the Kt/V urea ratio. Because monitoring for other solutes such as calcium and creatinine is theoretically available, clinical applications will continue to increase in the future.
Nonsurgical Infarctectomy in Acute Experimental Myocardial Infarction
Authors: Stamatelopoulos  , Saridakis  , Chatzis  , Kalandaridou  , Desses  , Lymperidis  , Giannopoulos  , Moulopoulos
Published: March 2003

This study examines whether a catheter mounted left intraventricular balloon may prevent left ventricular (LV) dysfunction following acute experimental myocardial infarction. In 10 anesthetized pigs, multiple coronary arterial ligations were applied around the apex of the heart. LV end‐diastolic pressure (LVEDP), aortic flow (AF), and LV long and short axis fractional shortening (FS) were measured before and at 15 min intervals after ligations. At the 60th min after ligation, the LV long axis FS and AF decreased by 7.2 ± 2.6% (p < 0.05) and 13.25 ± 2.68% (p < 0.01), respectively, and the LVEDP increased by 4.3 ± 1.1 mm Hg (p < 0.01) while no change was noted in the LV short axis FS. An intraventricular catheter mounted nonpulsating balloon was positioned over the endocardium of the infarcted area at the LV apex. Inflation of the nonpulsating balloon to an optimal volume, which was found to be equal to 8–10% of the LV end‐diastolic volume, resulted in a reduction (by 3.8 ± 1.2 mm Hg, p < 0.01) of the already increased LVEDP and in an increase (by 6.6 ± 2.1%, p < 0.05) in the LV short axis FS while no statistically significant change was noted in the AF and LV long axis FS. It is concluded that an intraventricular catheter mounted balloon patch positioned over the endocardium of the infarcted area may ameliorate early LV dysfunction, possibly by interfering with the functional geometry of the LV contraction.
Characterization of Antithrombotic Activity of Lumbrokinase‐Immobilized Polyurethane Valves in the Total Artificial Heart
Authors: Park Yongdoo , Ryu Eunsook , Kim Hyunjeong , Jeong Jaeseung , Kim Jinhee , Shim Jaehee , Jeon Sungmin , Jo Youngho , Kim Wongon , Min Byounggoo
Published: March 2003

Thirty ng/mm2 lumbrokinase, a potent fibrinolytic enzyme, was immobilized in a Korean type total artificial heart (KORTAH) valve by photoreaction; polyallylamine was used as a photoreactive linker. Lumbrokinase‐immobilized polyurethane valves were then fitted to the total artificial hearts of 3 healthy 50 kg lambs. In the control lamb, the valves were untreated; in one other, only valves on the right were treated; and in the remaining animal, only those on the left. Implants were in place for up to 3 days, and cardiac output was 5 L/min. To facilitate thrombus formation, low doses of heparin were administered. In the control lamb, thrombi was observed only in the inlet parts of the valves. In the other 2 experiments, thrombi formed in untreated control valves but not in lumbrokinase treated valves. The grade of thrombus formation in untreated valves was 1.06 ± 1.37 versus 0 ± 0 in the treated part by one‐sided Student's t‐test (p < 0.1). After implantation, fibrinolytic activity was only observed in treated valves by fibrin plate methods. The proteolytic activity of the treated valves was 3 times higher than that of untreated valves using the azocasein method. These data show that lumbrokinase treated polyurethane valves lead to decreased thrombus formation in vivo and that their biocompatibility is therefore greater than that of untreated valves.
Bioprosthetic Heart Valves–Replacing Order with Chaos: Electron Microscopic Study
Authors: Datta Debatosh , Kundu Prabuddha K. , Bandyopadhyay Bhaskar N.
Published: March 2003

Rheumatic heart disease is a significant clinical entity in young children, especially in the developing world. One of the major long‐term effects of ill managed rheumatic fever is irreversible damage to the cardiac valve leaflets, primarily on the left side. With the limited success of currently available mechanical and bioprosthetic valves, there is an urgent need for new directions in bioprosthetic valves, both in material, including source, degree of fixation, surface, bulk modifications, etc., and design. In the present paper, new proposals in the material selection and fabrication of bioprosthetic valves are proposed based on electron microscopic studies of natural valve leaflets and the pericardial surface. Current approaches for bioprosthetic valve fabrications include the wide use of the pericardium as a leaflet material. The present study indicates a need for nondestructive surface examination of pericardial sheets for the elimination of areas of surface voids resulting from gross fiber disorientation. Also, there seems to be a need for incorporation of an in situ fiber renewal mechanism in bioprosthetic leaflets to emulate the natural valve more closely. Apparently natural leaflets have built‐in fiber renewal mechanism(s).
Flow Visualization Analysis for Evaluation of Shear and Recirculation in a New Closed‐Type, Monopivot Centrifugal Blood Pump
Authors: Asztalos Balázs , Yamane Takashi , Nishida Masahiro
Published: March 2003

Abstract: Flow visualization has great potential in analyzing flow patterns of centrifugal blood pumps to locate possible hemolysis and thrombus formation sites. This study focused on the said phenomena thought to correlate with areas of high shear velocity and stagnation and analyzed a new closed‐type centrifugal blood pump. As a result of analyzing the flow of inlet and front gap of the impeller, flow in the front gap was approximately 30% of the external flow. Visualization in the back gap showed sufficient exchange also. Analysis in the volute area and around the washout holes revealed high shear locations and quantified the highest shear velocity. Maximum shear on the volute wall was found to be 9,000–19,000 s−1 and was located in the 0.2‐mm vicinity of the wall. Based on these results, previous hemolysis tests, and small pump size, one concludes that the analyzed closed‐type centrifugal pump has a relatively smooth flow suitable for a totally implantable artificial heart.
Preliminary Study on the New Self‐Closing Mechanical Mitral Valve
Authors: Naemura K. , Umezu M. , Dohi T.
Published: March 2003

Abstract: A natural mitral valve starts closing before systole. Conventional mechanical mitral valves start their closing motion after systole. In order to let the mechanical mitral valves start closing before systole, we propose a new self‐closing valve by adjusting the center of gravity of the leaflet. As a first step, we adjusted the center of gravity by attaching a block of lead to the leaflet of a CarboMedics bileaflet valve and evaluated it using a pulse duplicator and an x‐ray high‐speed video camera. Comparative study was conducted under 60 bpm and 4 L/min as the mean flow rate. It was clarified that the self‐closing valve started closing before systole, no influence on inflow volume was found, the final closing speed of the self‐closing valve just before complete closure was slower than the conventional valve (1.9–0.34 m/s), a design strategy of a self‐closing valve (sewing ring diameter 29 mm) was obtained from the experiment that momentum of inertia of the leaflet should be less than 14.9 × 10−9 kg·m2 and the torque caused by gravity should be more than 4.2 × 10−6 N · m, and only one leaflet should be designed as self‐closing, and surgeons need to pay attention to the positioning of the two leaflets. In conclusion, the preliminary study showed the ability of starting to close before systole and the design strategy for future prototyping.
Long‐Term Electromyogram Recording from the Posterior Cricoarytenoid Muscle as a Potential Biological Trigger for Phrenic Pacing: Results of an Animal Study
Authors: Lanmüller Hermann , Girsch Werner , Sauermann Stefan , Schwendenwein Ilse , Unger Ewald , Bijak Manfred , Rafolt Dietmar , Mayr Winfried
Published: March 2003

Abstract: Diaphragm pacing has been used to restore respiration in approximately 1,000 patients worldwide suffering from high quadriplegia or from central alveolar hypoventilation syndrome. Compared with conventional mechanical ventilation, electrophrenic respiration (EPR) reduces the risk of pulmonary infections and increases the mobility of patients. Voluntary activation of the pacemaker during speech would improve patients' quality of life and allow application of EPR in a more physiological way. An animal study was performed to investigate the electromyogram (EMG) of the posterior cricoarytenoid (PCA) muscle and the movement of the glottis via impedance measurement (electroglottography) with the aim to examine reproducibility and stability of the recordings from the PCA muscle as a potential biological trigger for a phrenic pacemaker. The EMG of the PCA muscle was recorded via implanted electrodes for a 200 day period. The EMG signal proved stable for that period, artifacts caused by movements can be suppressed, and swallowing can be detected. In contrast, impedance measurement to detect movement of the glottis proved not useful. Based on the results of this study, the use of the PCA EMG as a biological trigger for a phrenic pacemaker has to be considered a realistic option.
Belt Worn Control System and Battery for the Percutaneous Model of the Jarvik 2000 Heart
Authors: Jarvik  , Scott  , Morrow  , Takecuhi
Published: March 2003

A belt worn controller and lithium‐ion battery pack have been developed for use with the initial clinical trials of the Jarvik 2000 heart. Patient interface considerations, safety, and simplicity were major design inputs for the system. The controller was developed using all analog technology to avoid difficulties with electromagnetic interference (EMI), to minimize susceptibility to electrostatic discharge, and to avoid the need for software validation. Manual control of pump speed is accomplished by a patient operated knob, according to physician instructions for rest and exercise for each individual patient. The system includes alarms and indicators which show the following: the amount of remaining battery charge, if the battery is low and needs replacement, the power in watts being consumed, if the power consumed is above 15 W, if the pump is running below the selected speed setting, and if the pump stops. The control box, curved to be worn on the belt, is only 2.5 inches high for comfort when sitting. The battery pack, also form fitted for patient comfort, weighs just over 1½ pounds and supplies 65 W‐h of energy storage, sufficient to run the device for over 8 h at nominal load.
A Centrifugal Pump Driven Tidal Flow Extracorporeal Membrane Oxygenation System Tested with Neonatal Mock Circulation
Authors: Trittenwein Gerhard , Kölbl Reinhard , Trittenwein Hildegard , Golej Johann , Burda Gudrun , Hermon Michael , Pollak Arnold
Published: March 2003

In 1993, Chevalier published his experiences with tidal flow venovenous extracorporeal membrane oxygenation (ECMO) featuring a single lumen cannula, nonocclusive roller pump, and alternating clamps. Using a neonatal mock circulation (NMC), which enables different hemodynamic states for neonatal ECMO research, the tested hypothesis was that it is possible to create a centrifugal pump driven tidal flow neonatal venovenous ECMO system. Additionally, the resulting hemodynamic effects in a condition of circulatory impairment were investigated. The ECMO circuit tested was assembled using a pediatric centrifugal pump head, a distensible reservoir, and a rotary clamp separating drainage from the injection phase. Using the NMC, end tidal volumes, mock circulation flow, and arterial and venous pressures were measured at different pump speeds after the drainage and injection phases. Effective venovenous ECMO flow (evvEF) was calculated. Mock circulation baseline values (ECMO clamped) were compared to values during tidal flow ECMO. At 3,000 rpm, a centrifugal pump speed of 75 ml/kg/min evvEF was reached, and it increased with higher pump speeds. At this point, the end tidal mock circulation flow (representing cardiac output) after drainage differed significantly from that during the injection phase (p < 0.01) but not from the baseline value. The end tidal arterial and venous pressures after the drainage phase were found to be significantly decreased compared to the baselines (p < 0.01). In conclusion, a centrifugal pump driven tidal flow venovenous ECMO system can be created enabling sufficient tidal volumes. Tested in the described NMC simulating posthypoxic circulatory impairment, significant hemodynamic effects could be demonstrated. Animal experiments for confirmation are necessary.
Sealing Properties of Mechanical Seals for an Axial Flow Blood Pump
Authors: Tomioka Jun , Mori Toshio , Yamazaki Kenji , Koyanagi Hitoshi
Published: March 2003

A miniature intraventricular axial flow blood pump for left ventricular support is under development. One of the key technologies required for such pumps is sealing of the motor shaft. In this study, to prevent blood backflow into the motor side, mechanical seals were developed and their sealing properties investigated. In the experimental apparatus, the mechanical seal separated the bovine blood on the chamber side from the cooling water on the motor side. A leakage of the blood was measured by inductively coupled plasma (ICP) light emission analysis. The rate of hemolysis was measured by the cyanmethemoglobin method. Frictional torque acting on the shaft was measured by a torque transducer. In the experiments, the rotational speed of the shaft was changed from 1,000 to 10,000 rpm, and the contact force of the seal faces was changed from 1.96 to 4.31 N. To estimate lubrication regimes, the Stribeck curve, a diagram of the coefficient of friction against the bearing characteristic G number, was drawn. The results of the experiments showed that both the leakage of blood and the rate of hemolysis were very small. The friction loss was also very small. The mechanical seal was operated in various lubrication regimes, from a fluid lubrication regime to a mixed lubrication regime.
Development of Design Methods for a Centrifugal Blood Pump with a Fluid Dynamic Approach: Results in Hemolysis Tests
Authors: Masuzawa Toru , Tsukiya Tomonori , Endo Seiko , Tatsumi Eisuke , Taenaka Yoshiyuki , Takano Hisateru , Yamane Takashi , Nishida Masahiro , Asztalos Balazs , Miyazoe Yuki , Ito Kazuyuki , Sawairi Toshio , Konishi Yoshiaki
Published: March 2003

The purpose of this study was to examine the relationship between local flow conditions and the hemolysis level by integrating hemolysis tests, flow visualization, and computational fluid dynamics to establish practical design criteria for centrifugal blood pumps with lower levels of hemolysis. The Nikkiso centrifugal blood pump was used as a standard model, and pumps with different values of 3 geometrical parameters were tested. The studied parameters were the radial gap between the outer edge of the impeller vane and the casing wall, the position of the outlet port, and the discharge angle of the impeller vane. The effect of a narrow radial gap on hemolysis was consistent with no evidence that the outlet port position or the vane discharge angle affected blood trauma in so far as the Nikkiso centrifugal blood pump was concerned. The radial gap should be considered as a design parameter of a centrifugal blood pump to reduce blood trauma.
Development of the Membrane Autotransfusion System Prototype‐II: MATS‐II
Authors: Fukunaga Ken , Shimoyama Takashi , Sawada Koji , Sueoka Akinori , Nosé Yukihiko
Published: March 2003

Abstract: This article is the second of a two‐part series describing a membrane autotransfusion system, MATS, utilizing plasmapheresis technology. Based on experiences obtained from the first prototype (MATS‐I), optimum blood filtration parameters with refined blood and flux pump synchronization were put into an original CPU‐board and loaded on a miniaturized, self‐operative, and preclinical prototype (MATS‐II). This study was conducted to evaluate the MATS‐II using diluted blood of various hematocrit concentrations. The results proved that this device could concentrate 4,000–10,000 ml of various hematocrit concentrations into higher than 40% while automatically controlling the flow speed from 250 to 400 ml/min. Also, no significant damage was generated to the red blood cells (RBC). Moreover, the MATS‐II salvaged over 90% of platelets together with the RBC. These results suggest that the MATS‐II achieves all clinical requirements of an autotransfusion device; it is a continuous hemoconcentration device with minimum damage to cellular components of the blood.
Cytokine Release and Serum Lipoprotein (a) Alterations During Hemodialysis
Authors: Tzanatos Helen A. , Agroyannis Basil , Chondros Costas , Kapetanaki Antigoni , Fourtounas Costas , Soubassi Lygeri , Kopelias Ioannis
Published: March 2003

Abstract: It has been reported recently that a number of cytokines, mainly tumor necrosis factor α (TNFα), interleukin (IL)‐1β, and IL‐6, can alter lipid metabolism and produce hyperlipidemia. Studies in hemodialysis (HD) patients have demonstrated increased production of these cytokines during HD. In order to investigate any possible relationship between changes of cytokines and lipid concentrations during HD in the serum of 25 uremic patients on chronic HD using modified cellulose membranes, TNFα, IL‐1β, IL‐6, total cholesterol (TC), triglycerides (TG), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), lipoprotein a (Lp[a]), and total proteins were measured immediately before (pre‐HD) and after HD (post‐HD), in one session. The post‐HD values were corrected according to the hemoconcentration based on the changes in serum total proteins. Serum TNFα and IL‐1β levels were significantly increased from 38.24 ± 17.85 pg/ml and 2.60 ± 3.64 pg/ml pre‐HD to 48.86 ± 25.21 and 3.49 ± 4.08 pg/ml post‐HD, p < 0.001 and p < 0.05 respectively. Also Lp(a) levels presented a statistically significant increase post‐HD and were almost doubled (pre‐HD: 15.41 mg/dl, to post‐HD: 27.39 mg/dl, p < 0.05). Serum IL‐6 as well as serum TC, TG, HDL‐C, and LDL‐C did not show any statistically significant alterations during HD. A significant positive correlation was detected between TNFα and Lp(a) values post‐HD (r: 0.413, p: 0.04), but not between pre‐HD values. No further relationship between serum cytokines and the other estimated lipid parameters was observed, either between pre‐ or post‐HD values. Our results indicate that release of TNFα and IL‐1β during HD have no effect on serum lipids concentration, except on Lp(a). It seems that the acute rise of this lipoprotein during hemodialysis may be related with the TNFα overproduction.
Oxygen Transfer in a Diffusion‐Limited Hollow Fiber Bioartificial Liver
Authors: Hay P.D. , Veitch A.R. , Smith M.D. , Cousins R.B. , Gaylor J.D.S.
Published: March 2003

Abstract: A mathematical model was developed to predict oxygen transport in a hollow fiber bioartificial liver device. Model parameters were taken from the Hepatix ELAD configuration; a blood perfused hollow fiber cartridge with hepatocytes seeded in the extracapillary space. Cellular oxygen uptake is based on Michaelis‐Menten kinetics, and nonlinear oxygen transport in the blood is considered. The effect of modulating three important parameters is investigated, namely, the Michaelis‐Menten constants Vm (volumetric oxygen consumption of the hepatocytes) and Km (half‐saturation constant), and hollow fiber oxygen permeability. A computer implementation of the model is used to assess whether a given cell mass could be maintained within such a device. The results suggest that liver cell lines possessing low rates of oxygen consumption could be maintained if membranes of sufficiently high oxygen permeability are used. For primary hepatocytes, which have much higher oxygen demands, radial transport of oxygen is rate limiting, and the axial‐flow hollow fiber cartridge is thus an inappropriate design for use as a bioartificial liver with primary hepatocytes.