bluuebunny/crossref_metadata_2025 huggingface dataset:
Dance/Movement Therapy for Children and Adolescents with Cancer
Authors: Cohen Susan O. , Walco Gary A.
Published: March 2003

PURPOSE
: Dance/movement therapy is introduced as a holistic approach to children's health issues, incorporating an array of medical, psychological, social, and spiritual issues.

OVERVIEW
: Dance/movement therapy, with its unique emphasis on nonverbal communication in assessment and treatment, is presented as an innovative therapeutic approach to address the comprehensive needs of children and adolescents with cancer. Dance/movement therapy assessment and intervention strategies are discussed in the context of cognitive, emotional, and social developmental processes, as well as models of stress and psychological adjustment in pediatric cancer.

CLINICAL IMPLICATIONS
: The inclusion of dance/movement therapy as part of the interdisciplinary team addressing the psychosocial needs of children and adolescents with cancer facilitates greater integration of factors related to coping. By its very nature, this modality offers constructs that promote holistic approaches to cancer care.
Perception of Chemotherapy Side Effects Cancer versus Noncancer Patients
Authors: Lindley Celeste , McCune Jeannine S. , Thomason Tracy E. , Lauder Dionne , Sauls Amy , Adkins Shelly , Sawyer William T.
Published: March 2003

purpose
: This study was conducted to identify and compare perceptions regarding the disruption in quality of life caused by chemotherapy side effects in patients with cancer receiving chemotherapy and in noncancer, chemotherapy‐naive patients.

description of study
: One hundred forty‐six patients with cancer and 224 patients without cancer completed two instruments to assess the perceived magnitude of 41 physical and psychosocial chemotherapy side effects. Instrument 1 used a 5‐point Likert scale (1 = not at all; 2 = a little bit; 3 = somewhat; 4 = quite a bit; and 5 = very much) to summarize patient responses to the question, “How much did or would each of the following side effects of chemotherapy bother you?” Instrument 2 was a serial ranking questionnaire that asked patients to select the 10 most bothersome side effects to numerically rank the top five. An index of the relative magnitude of chemotherapy side effects was calculated for each instrument.

results
: For patients with cancer, loss of hair 50%), changes in taste (46%), constantly being tired (42%), affects work duties (39%), changes in smell perception (35%) were most frequently perceived as bothering them “quite a bit” or “very much.” Nausea and vomiting were ranked 11th and 22nd, respectively. With instrument 2, the five side effects perceived as most troublesome were, in decreasing order: nausea, loss of hair, constantly tired, vomiting, and changes in the way things taste. For noncancer patients, those factors potentially bothersome “quite a bit” or “very much” were: financial hardship (82%), hardship on family (78%), vomiting (73%), shortness of breath (70%), and ability to perform work duties (69%). Via instrument 2, the top five side effects, in decreasing order were: vomiting, hardship on family, loss of hair, financial hardship, nausea, having to move close to a treatment center.

clinical implications
: Noncancer, chemotherapy‐naive patients perceived most chemotherapy‐associated side effects as having greater impact on the quality of life than did cancer patients who had received chemotherapy. These findings can be used to direct patient education, education of the public, specific materials concerning cancer chemotherapy. The expertise of various members of the healthcare team can maximize the patient's comprehension of the adverse effects of the treatment options. The physician's knowledge of the overall treatment plan can assist in patient understanding; oncology pharmacists nurses are in a unique position to educate patients their families regarding potential chemotherapy side effects.
Lymphedema in Women Treated for Breast Cancer
Authors: Loudon Lisa , Petrek Jeanne
Published: March 2003

Purpose:

The purpose of this report is to discuss the etiologic factors, prevention, and current treatment options for lymphedema, which may occur after breast cancer.

Overview:

Lymphedema can develop in the breast cancer patient as a result of the interruption of lymphatic flow from postsurgical, postradiation, and infectious causes. It can present at various points after breast cancer treatment and may range from mild to a seriously disabling enlargement. Because lymphedema is permanent, the goal of treatment options is the control of edema, and a multidimensional approach to care is often needed.

Clinical implications:

In the past, there has been limited research in this area. Because lymphedema is essentially an incurable condition, healthcare providers should be aware of techniques such as sentinel‐node biopsy that could significantly decrease its incidence. In addition, it is important that each patient's treatment include education and prevention precautions.
Hereditary stability and variation in evolution and development
Authors: Thaler David S.
Published: March 2003

Evolution and development are both lineage processes but are often conceptualized as occurring by different and mutually exclusive mechanisms. It is conventionally asserted that evolution occurs via the random generation of diversity and the subsequent survival of those that pass selection. On the other hand, development is too often presented as proceeding via the unfolding of a deterministic program encoded in the DNA sequence. In biology, universal generalizations are rare and dogmas are often wrong for particular cases. Deterministic mechanisms contribute some of the new DNA sequences that subsequently become substrates for natural selection. Conversely, stochastic and selective mechanisms are intrinsic to development, and also to maintenance of the immune, and possibly, nervous systems. Cancer appears to be another process that straddles distinctions between evolutionary and developmental modes of hereditary change and stabilization. DNA sequence changes are an essential feature of many cancers, but there are also aspects of the disease similar to developmental lineage gone awry. The literature suggests that the cellular changes that give rise to cancer occur by mechanisms commonly associated with both evolutionary and developmental lineage pathways.
Barnacle duplicate engrailed genes: divergent expression patterns and evidence for a vestigial abdomen
Authors: Gibert Jean‐Michel , Mouchel‐Vielh Emmanuèle , Quéinnec Eric , Deutsch Jean S.
Published: March 2003

SUMMARY Cirripedes (barnacles) are crustaceans that are characterized by a very peculiar body plan, in particular by the lack of an abdomen. To study their body plan, we searched for their engrailed gene. We found two engrailed (en.a/en.b) genes in cirripedes. The two engrailed genes of the rhizocephalan barnacle Sacculina carcini are expressed in the posterior compartment of developing segments and appendages. When the neuroectoderm differentiates into epidermis and neuroderm the expression patterns of en.a and en.b diverge dramatically. en.a expression fades in segment epidermis whereas it is subsequently detected ventrally in reiterated putative neural cells. At the same time, en.b expression increases in the epidermis, which makes it a very good segmentation marker. Five tiny en.b stripes are observed between the sixth thoracic segment and the telson. We interpret these stripes as the molecular definition of vestigial abdominal segments, being the remnant of an ancestral state in keeping with the bodyplan of maxillopod crustaceans. engrailed expression is the first molecular evidence for a segmented abdomen in barnacles.
Additional hox clusters in the zebrafish: divergent expression patterns belie equivalent activities of duplicatehoxB5genes
Authors: Bruce Ashley E. E. , Oates Andrew C. , Prince Victoria E. , Ho Robert K.
Published: March 2003

SUMMARYThe evolution of metazoan body plans has involved changes to the Hox genes, which are involved in patterning the body axis and display striking evolutionary conservation of structure and expression. Invertebrates contain a single Hox cluster whereas tetrapods possess four clusters. The zebrafish has seven unlinked hox clusters, a finding that is difficult to reconcile with the notion that genomic complexity, reflected by Hox cluster number, and morphological complexity are causally linked, as the body plan of the zebrafish is not obviously more complex than that of the mouse or human. Why have the additional hox genes in zebrafish been conserved?  To address the role of these additional zebrafish hox genes, we have examined the duplicatehoxB5genes,hoxB5a, andhoxB5b.Conservation of gene duplicates can occur when one gene acquires a new function (neofunctionalization), or when the ancestral function is divided between the two duplicates (subfunctionalization).hoxB5aandhoxB5bare expressed in distinct domains, and their combined expression domain is strikingly similar to that of singleHoxb5genes in other species. The biochemical functions encoded by the two genes were studied by overexpression, which resulted in identical developmental defects in the anterior hindbrain and cranial neural crest, suggesting strongly thathoxB5aandhoxB5bhave equivalent biochemical properties with respect to early development. From these studies, we conclude that conservation ofhoxB5aandhoxB5bis likely the result of division of the ancestralHoxb5function between the two genes, without significant changes in biochemical activity. These results suggest a resolution to the conundrum of the extra hox genes and clusters in the zebrafish, since if any of the additional hox genes in the zebrafish are similarly subfunctionalized, they are unlikely to supply novel genetic functions. Thus, the morphological complexity potentially conferred by the majority of additional zebrafish hox clusters may not be substantially greater than that conferred by the four tetrapod clusters.
Divergent structure and function of the bicoid gene in Muscoidea fly species
Authors: Shaw Philip J. , Salameh Ahmad , McGregor Alistair P. , Bala Sendu , Dover Gabriel A.
Published: March 2003

SUMMARY We have investigated the evolution of the bicoid (bcd) gene in fly species of the Muscoidea Superfamily. We obtained the complete bcd sequence from the housefly Musca domestica and found polymorphism in the coding region among Musca strains. In addition to Musca, we cloned most of the bcd coding sequences from two blowfly species Calliphora vicina and Lucilia sericata. The 5′ and 3′ regulatory regions flanking the Musca bcd gene are widely diverged in sequence from Drosophila; however, some important sequence motifs identified in Drosophila bcd are present. The predicted RNA secondary structures of the 3′ UTRs are similar, despite sequence divergence. Comparison of Bicoid (Bcd) proteins shows a serine‐rich domain of unknown function is present in the Muscoidea species, but is absent in other species. The in vivo function of bcd in Musca was tested by RNAi to mimic loss of function phenotype. We obtained a head defect phenotype similar to weak bcd alleles of Drosophila. Although our comparisons initially suggest functional conservation between species, closer inspection reveals significant differences. Divergence of structural motifs, such as regulatory elements in flanking regions and conservation of protein domains in some species but not in others, points to functional divergence between species. We suggest that the larger embryonic size in Muscoidea species restricts the morphogenetic activity of a weak Bcd activator, which has evolved a more specialized role in head determination and lost some functions in thoracic development.
Developmental drive: an important determinant of the direction of phenotypic evolution
Authors: Arthur Wallace
Published: March 2003

SUMMARYOver any period of evolutionary time, the prevailing ontogenetic trajectory within a lineage may either recur unchanged from generation to generation (stasis) or alter (developmental reprogramming). A key question about reprogramming is whether it exhibits intrinsic biases in favor of some sorts of change and against others, which may be referred to respectively as “drive” and “constraint.” A simple logical argument suggests that both drive and constraint should be common, and conversely that cases of equiprobable modification in various phenotypic directions should be relatively rare. These proposals, that drive and constraint exist and that they are common, appear to be widely accepted, even among neo‐Darwinians, who are sometimes portrayed as rejecting them. What is more controversial is that developmental drive (and constraint) can have a powerful influence on the direction of evolutionary change. It is argued that such an influence will occur, and indeed may be pervasive.
Gene expression and larval evolution: changing roles ofdistal‐lessandorthodenticlein echinoderm larvae
Authors: Lowe Christopher J. , Issel‐Tarver Laurie , Wray Gregory A.
Published: March 2003

SUMMARYWe describe the expression of the homeobox genesorthodenticle(Otx) anddistal‐less(Dlx) during the larval development of seven species representing three classes of echinoderms: Holothuroidea, Asteroidea, and Echinoidea. Several expression domains are conserved between species within a single class, including Dlx expression within the brachiolar arms of asteroid larvae and Otx expression within the ciliated bands of holothuroid larvae. Some expression domains are apparently conserved between classes, such as the expression of Dlx within the hydrocoel (left mesocoel) in all three classes. However, several substantial differences in expression domains among taxa were also evident for both genes. Some autapomorphic (unique derived) features of gene expression are phylogenetically associated with autapomorphic structures, such as Dlx expression within the invaginating rudiment of euechinoids. Other autapomorphic gene expression domains are associated with evolutionary shifts in life history from feeding to nonfeeding larval development, such as Otx expression within the ciliated bands of a nonfeeding holothuroid larva. Similar associations between evolutionary changes in morphology and life history mode with changes in regulatory gene expression have also been observed in arthropods, urochordates, and chordates. We predict that recruitment of regulatory genes to a new developmental role is commonly associated with evolutionary changes in morphology and may be particularly common in clades with complex life cycles and diversity of life history modes. Caution should be used when making generalizations about gene expression and function based on a single species, which may not accurately reflect developmental processes and life histories of the phyla to which it belongs.
The best of all worlds or the best possible world? Developmental constraint in the evolution of β‐tubulin and the sperm tail axoneme
Authors: Nielsen Mark G. , Raff Elizabeth C.
Published: March 2003

SUMMARY Through evolutionary history, some features of the phenotype show little variation. Stabilizing selection could produce this result, but the possibility also exists that a feature is conserved because it is developmentally constrained—only one or a few developmental mechanisms can produce that feature. We present experimental data documenting developmental constraint in the assembly of the motile sperm tail axoneme. The 9+2 microtubule architecture of the eukaryotic axoneme has been deeply conserved. We argue that the quality of motility supported by axonemes with this morphology explains their long conservation, rather than a developmental necessity for the 9+2 architecture. However, our functional tests in Drosophila spermatogenesis reveal considerable constraint in the coevolution of testis‐specific β‐tubulin and the sperm tail axoneme. The evolution of testis β‐tubulins used in insect sperm tail axonemes is highly punctuated, indicating some pressure acting on their evolution. We provide a mechanistic explanation for their punctuated evolution by testing structure–function relationships between testis β‐tubulin and the motile axoneme in D. melanogaster. We discovered that a highly conserved sequence feature of β‐tubulins used in motile axonemes is needed to specify central pair formation. Second, our data suggest that cooperativity in the function of internal β‐tubulin amino acids is needed to support the long axonemes characteristic of Drosophila sperm tails. Thus, central pair formation constrains the evolution of the axoneme motif, and intramolecular cooperativity makes the evolution of the internal residues path dependent, which slows their evolution. Our results explain why a highly specialized β‐tubulin is needed to construct the Drosophila sperm tail axoneme. We conclude that these constraints have fixed testis‐specific β‐tubulin identity in Drosophila.
Integrative biology and the developing limb bud1
Authors: Innis Jeffrey W. , Margulies Elliott H. , Kardia Sharon
Published: March 2003

SUMMARY The identification or selective construction of mutations within genes has allowed researchers to explore the downstream effects of gene disruption. Although these approaches have been successful, a limitation in our assessment of the consequences of conditional changes, and thereby our understanding of roles or function of genes, limits the degree to which we examine the effects of our manipulations. It is also clear that linear associations are incorrect models for describing development, and newer methods now give us an opportunity to practice an integrative biology. In our attempts to explore the consequences of Hoxa13 disruption in mice and humans, it has become clear that a better understanding of the consequences of gene alteration may be achievable by taking a broader approach with a long‐term view. Fundamental questions regarding Hox gene function in vertebrates, including those related to the number of target genes; the degree of overlap of target gene regulation among paralogs; the magnitude of modulation exerted; and the identity of genes that are activated versus repressed need to be explored if a more thorough mechanistic understanding is to be achieved. To begin to address these questions, we undertook a comprehensive analysis of the expression of genes within developing limb buds of mice, and here we present some of our preliminary results. Our efforts will further (1) the exploration of the broader genetic relationships of expressed genes, (2) the determination of parallels or variations in target usage for a given gene in different tissues and between different organisms, (3) the evaluation of limb patterning mechanisms in other animal model systems, and (4) the exploration of gene expression hierarchies regulated by HOX proteins in developmental systems.
Avian thyroid development in chemically contaminated environments: is there evidence of alterations in thyroid function and development?
Authors: McNabb F. M. Anne , Fox Glen A.
Published: March 2003

SUMMARY Poor reproductive success, developmental abnormalities, and behavioral alterations in fish‐eating birds in some Great Lakes areas have led to more than 35 years of toxicological studies and residue monitoring of herring gull (Larus argentatus) populations. Polyhalogenated aromatic hydrocarbons (PHAHs), especially polychlorinated biphenyls (PCBs), are widespread contaminants in the Great Lakes ecosystem. The introduction of regulations and elimination of point sources since the 1970s have resulted in decreased PHAHs in fish‐eating bird eggs and tissues. PCB exposure is associated with thyroid disruption (hypothyroidism) in mammals, but much less is known of PCB effects on avian thyroid function. Our 1998–2000 studies of herring gulls from the Great Lakes show that both pipping embryos and prefledglings from highly contaminated sites have marked depletion of thyroid gland hormone stores compared with similarly aged gulls at the reference sites. However, organismal hypothyroidism was not apparent in many embryo and chick collections where severe depletion of thyroid gland hormone was observed. Adults, sampled at two high PCB sites and a low PCB site in the Great Lakes and the maritime reference colony in 2001, showed no differences in organismal thyroid status across sites, but gulls from the high sites had enlarged thyroid glands and depressed thyroid gland hormone stores. Here we discuss the evidence that ecological exposure to PHAHs are responsible for thyroid deficiencies in gulls and that during development these deficiencies lead to developmental abnormalities in young gulls from highly contaminated Great Lakes sites.
Early differentiation and migration of cranial neural crest in the opossum, Monodelphis domestica
Authors: Vaglia Janet L. , Smith Kathleen K.
Published: March 2003

SUMMARY Marsupial mammals are born at a highly altricial state. Nonetheless, the neonate must be capable of considerable functional independence. Comparative studies have shown that in marsupials the morphogenesis of many structures critical to independent function are advanced relative to overall development. Many skeletal and muscular elements in the facial region show particular heterochrony. Because neural crest cells are crucial to forming and patterning much of the face, this study investigates whether the timing of cranial neural crest differentiation is also advanced. Histology and scanning electron microscopy of Monodelphis domestica embryos show that many aspects of cranial neural crest differentiation and migration are conserved in marsupials. For example, as in other vertebrates, cranial neural crest differentiates at the neural ectoderm/epidermal boundary and migrates as three major streams. However, when compared with other vertebrates, a number of timing differences exist. The onset of cranial neural crest migration is early relative to both neural tube development and somite formation in Monodelphis. First arch neural crest cell migration is particularly advanced and begins before any somites appear or regional differentiation exists in the neural tube. Our study provides the first published description of cranial neural crest differentiation and migration in marsupials and offers insight into how shifts in early developmental processes can lead to morphological change.
Covalent Linkage of Recombinant Hirudin to a Novel Ionic Poly(Carbonate) Urethane Polymer with Protein Binding Sites: Determination of Surface Antithrombin Activity
Authors: Phaneuf Matthew D. , Szycher Michael , Berceli Scott A. , Dempsey Donald J. , Quist William C. , LoGerfo Frank W.
Published: March 2003

Surface thrombus formation on implantable biomaterials such as polyurethane is a major concern when utilizing these materials in the clinical setting. Thrombin, which is responsible for thrombus formation and smooth muscle cell activation, has been the target of numerous surface modification strategies in an effort to prevent this phenomenon from occurring. The purpose of this study was to covalently immobilize the potent, specific antithrombin agent recombinant hirudin (rHir) onto a novel polyurethane polymer synthesized with carboxylic acid groups which served as protein attachment sites. The in vitro efficacy of thrombin inhibition by this novel biomaterial surface was then evaluated. Bovine serum albumin (BSA), which was selected as the basecoat protein, was reacted with sulfo‐SMCC in a 1:50 molar ratio. This BSA‐SMCC complex was then covalently linked to the carboxylated polyurethane (cPU) surface via the crosslinker EDC (cPU‐BSA‐SMCC). This cPU‐BSA‐SMCC surface was then reacted with Traut's‐ modified 125I‐rHir, a procedure which created free sulfhydryl groups on rHir (cPU‐BSA‐SMCC‐S‐125I‐rHir). Using these crosslinking procedures, the cPU‐BSA‐SMCC‐S‐125I‐rHir segments bound 188 ± 40 ng/cm2 (n =60) whereas the controls with nonspecifically bound 125I‐rHir (Mitrathane + EDC + BSA +125I‐rHir‐SH and cPU‐BSA +125I‐rHir‐SH) bound 13 ± 8 ng/cm2 and 4 ± 8 ng/cm2, respectively. Evaluation of these cPU‐BSA‐SMCC‐S‐125I‐rHir segments for 131I‐thrombin inhibition using a chromogenic assay for thrombin showed that a maximum of 2.64 NIHU thrombin was inhibited in contrast to the controls which inhibited 0.76 and 0.70 NIHU. Controls with nonspecifically bound 125I‐rHir also had 0.31 and 0.76 NIHU 131I‐thrombin adherent to their respective surfaces whereas the maximum 131I‐thrombin binding to the cPU‐BSA‐SMCC‐S‐rHir segments was 1.51 NIHU. Exposure to 131I‐thrombin did not result in any release of covalently bound 125I‐rHir from the cPU‐BSA‐SMCC‐S‐125I‐rHir segments. Thus, these results demonstrate that rHir can be covalently bound to this novel polyurethane surface and still maintain potent antithrombin activity.
Implantable Control, Telemetry, and Solar Energy System in the Moving Actuator Type Total Artificial Heart
Authors: Ahn Jae Mok , Lee Jung Hoon , Choi Sung Wook , Kim Wook Eun , Omn Kyong Sik , Park Seong Keun , Kim Won Gon , Roh Joon Ryang , Min Byoung Goo
Published: March 2003

The moving actuator type total artificial heart (TAH) developed in the Seoul National University has numerous design improvements based upon the digital signal processor (DSP). These improvements include the implantability of all electronics, an automatic control algorithm, and extension of the battery run‐time in connection with an amorphous silicon solar system (SS). The implantable electronics consist of the motor drive, main processor, intelligent Li ion battery management (LIBM) based upon the DSP, telemetry system, and transcutaneous energy transmission (TET) system. Major changes in the implantable electronics include decreasing the temperature rise by over 21°C on the motor drive, volume reduction (40 × 55 × 33 mm, 7 cell assembly) of the battery pack using a Li ion (3.6 V/cell, 900 mA · h), and improvement of the battery run‐time (over 40 min) while providing the cardiac output (CO) of 5 L/min at 100 mm Hg afterload when the external battery for testing is connected with the SS (2.5 W, 192 · 192, 1 kg) for the external battery recharge or the partial TAH drive. The phase locked loop (PLL) based telemetry system was implemented to improve stability and the error correction DSP algorithm programmed to achieve high accuracy. A field focused light emitting diode (LED) was used to obtain low light scattering along the propagation path, similar to the optical property of the laser and miniature sized, mounted on the pancake type TET coils. The TET operating resonance frequency was self tuned in a range of 360 to 410 kHz to provide enough power even at high afterloads. An automatic cardiac output regulation algorithm was developed based on interventricular pressure analysis and carried out in several animal experiments successfully. All electronics have been evaluated in vitro and in vivo and prepared for implantation of the TAH. Substantial progress has been made in designing a completely implantable TAH at the preclinical stage.
Peritoneal Dialysis Solutions for the 21st Century
Authors: Martis Leo , Chen Chi , Moberly James B.
Published: March 2003

Existing peritoneal dialysis (PD) solutions were formulated for the maintenance of fluid and electrolyte balance, correction of metabolic acidosis, and the removal of metabolic waste products. Solutions currently in development are designed to improve biocompatibility by neutralizing pH and reducing glucose degradation products. PD solutions developed for the 21st century will address major clinical needs related to the maintenance of adequate nutrition, improvement of cardiovascular comorbidity, preservation of peritoneal membrane function, and adequacy of dialysis. Nutrineal is the first example of a PD solution to address such a clinical need. Another example is a low sodium solution to improve sodium balance thereby reducing the incidence of hypertension and the need for antihypertensive medication. New solutions under investigation will employ additives to protect the peritoneal membrane during peritonitis and chronic PD and to optimize PD therapy via improvements in ultrafiltration and solute clearances. Examples include the use of antioxidants to reduce oxidative damage during peritonitis and the use of glycosaminoglycans or other additives to enhance ultrafiltration. Future concepts include remodeling of the peritoneum, for example, the use of mesothelial gene therapy to introduce metabolic and anabolic machinery to remove or perpetually recycle metabolic wastes. The 21st century promises to be an exciting and fruitful time for the investigation and development of new products for the improvement of PD therapy.
Cytotoxicity of Bile in Human Hep G2 Cells and in Primary Cultures of Rat Hepatocytes
Authors: Smirthwaite Amie D. , Gaylor John D. S. , Cousins Roderick B. , Helen Grant
Published: March 2003

There has been increasing interest in the development of a hepatocyte bioreactor for the treatment of acute hepatic failure; however, little is known about the effect of hepatocyte byproducts on the viability of the cells in the bioreactor environment. We investigated the effects of increasing concentrations of bile on the growth and viability of the human hepatoma cell line Hep G2 and on the cytochrome P‐450 content and dependent mixed function oxidase (MFO) activities, reduced glutathione (GSH) content, and glutathione S‐transferase (GST) activity of primary cultures of rat hepatocytes. Our purpose was to determine whether or not it would be necessary to pretreat the plasma from patients with acute liver failure to remove elevated bile concentrations which might be toxic to the hepatocytes in an artificial liver device. Bile was found to inhibit Hep G2 cell growth at concentrations as low as 0.1% and to decrease viability at concentrations above 0.5%. The cytochrome P‐450 and GSH contents and the activities of the MFO system and of GST were decreased in the primary cultures of hepatocytes following 24 h treatment with concentrations of bile at and above 0.5%. The MFO activities associated with different cytochrome P‐450 isoenzymes decreased to different extents in the presence of bile with the O‐dealkylation of pentoxyresorufin being more labile than that of ethoxyresorufin. Our data indicate that elevated bile concentrations are cytotoxic to liver cells, and it may be necessary to pretreat patient plasma to decrease its bile content to protect the cells during the clinical operation of a hepatocyte bioreactor device.
Performance of a Continuous Flow Ventricular Assist Device: Magnetic Bearing Design, Construction, and Testing
Authors: Allaire  , Hilton  , Baloh  , Maslen  , Bearnson  , Noh  , Khanwilkar  , Olsen
Published: March 2003

A new centrifugal continuous flow ventricular assist device, the CFVAD III, which is fully magnetic bearing suspended, has been developed. It has only one moving part (the impeller), has no contact (magnetic suspension), is compact, and has minimal heating. A centrifugal impeller of 2 inch outer diameter is driven by a permanent magnet brushless DC motor. This paper discusses the design, construction, testing, and performance of the magnetic bearings in the unit. The magnetic suspension consists of an inlet side magnetic bearing and an outlet side magnetic bearing, each divided into 8 pole segments to control axial and radial displacements as well as angular displacements. The magnetic actuators are composed of several different materials to minimize size and weight while having sufficient load capacity to support the forces on the impeller. Flux levels in the range of 0.1 T are employed in the magnetic bearings. Self sensing electronic circuits (without physical sensors) are employed to determine the impellar position and provide the feedback control signal needed for the magnetic bearing control loops. The sensors provide position sensitivity of approximately 0.025 mm. A decentralized 5 axis controller has been developed using modal control techniques. Proportional integral derivative controls are used for each axis to levitate the magnetically supported impeller.
Migration Resistant, Blood‐Compatible Plasticized Polyvinyl Chloride for [Medical and Related Applications
Authors: Lakshmi  , Jayakrishnan
Published: March 2003

Plasticized polyvinyl chloride (PVC), although not a blood‐compatible polymer, is the material of choice for the manufacture of blood bags and hemodialysis tubing throughout the world. PVC is usually plasticized with di‐(2‐ethylhexyl phthalate) (DEHP) to impart flexibility and low temperature properties to the final product. DEHP belongs to a class of agents called hypolipidemic hepatocarcinogens, and it migrates in small quantities into the storage medium such as blood, plasma, or serum, resulting in a number of toxic effects. It has been shown that the migration resistance and blood compatibility of flexible PVC could be significantly improved by grafting polyethylene glycol (PEG), the most blood‐compatible polymer known today, onto the surface of flexible PVC by the classical Williamson ether synthesis reaction. The technique is simple and versatile enough to produce blood‐compatible, migration resistant PVC surfaces for many medical applications. The method may also find use for preventing plasticizer migration from PVC cling films and polyvinylidene chloride films used extensively in food packaging.
Left Centrifugal Pump Cardiac Assist with Transseptal Percutaneous Left Atrial Cannula
Authors: Pavie  , Léger  , Nzomvuama  , Szefner  , Regan  , Vaissier  , Gandjbakhch
Published: March 2003

Left cardiac support postcardiotomy requires a second operation for removal of the atrial cannula following weaning from assistance. To avoid the risk of this procedure, we used a transseptal cannula prototype. The cannula was introduced percutaneously through the femoral vein and advanced into the left atrium guided by the finger of the surgeon. Optimal positioning of the tip of the cannula was verified by perioperative transesophageal echocardiography. A long arterial cannula was positioned in the descending aorta via the femoral artery and a Carmeda circuit with a centrifugal pump was connected to both cannulas. This procedure was used in 3 patients with low cardiac output who underwent emergency surgery, a 63‐year‐old patient referred for aortic and mitral valve replacement, a 54‐year‐old man for aortic valve replacement, and a 64‐year‐old patient in the acute phase of myocardial infarction after myocardial revascularization. The assistance was used systematically at the end of the operation. The assist flow was 1.2–2.6 L/min. The patients were all weaned from support between 18 h and 8 days later. No complications related to the device occurred. Both cannulas were removed surgically from the femoral vessels without reopening the chest. This new procedure is of interest for 2 reasons: the systematic implantation allows for early assistance, and the use of a percutaneous approach avoids the risk of reopening the chest. More cases are needed to confirm this initial good impression.
Cleveland Clinic Continuous Flow Blood Pump: Progress in Development
Authors: Golding Leonard , Medvedev Alexander , Massiello Alex , Smith William , Horvath David , Kasper Renee
Published: March 2003

The Cleveland Clinic continuous flow blood pump is the central element of our innovative ventricular assist system (IVAS). Recent progress has been made in the design/fabrication of a pulsatile mock loop, journal bearing materials testing, and evaluation of a system control algorithm. These results have allowed an acceleration of our program.
A Simple Neonatal Mock Circulation Enabling Pulsatility and Different Hemodynamical States for Neonatal ECMO Research: Application to Assess theEffect of a Centrifugal Pump Operated Neonatal ECMO System on the Circulation
Authors: Trittenwein G. , Zamberger A. , Trittenwein H. , Burda G. , Golej J. , Hermon M. , Pollak A.
Published: March 2003

AbstractIn neonates, extracorporeal membrane oxygenation (ECMO) is increasingly used for circulatory support, e.g., after cardiac surgery. For training purposes and for research, animal experiments are usually required, complicated by increasing social issues, high costs, and limited reproducibility. Therefore, we designed a mechanical neonatal mock circulation (NMC) model enabling pulsatility and various hemodynamic conditions commonly occurring in neonates. Connected to a flow and pressure reading interface, a computer assisted data management system was installed. A nonocclusive roller pump combined with stiff and elastic tubing segments (for aortic pressure regulation and venous capacity) as well as constant and variable resistance (and optionally a patent duct) are essential features of the NMC system. To show the investigational potential, we studied the influence of venoarterial and venovenous ECMO on the NMC performance during normal circulation, hypovolemia, high arterial resistance, the combination of both, and in low cardiac output. By assessing the significant effects of ECMO on the circulatory function of the NMC, its feasibility and investigational properties could be demonstrated.
Computational Fluid Dynamic Analyses to Establish Design Process of Centrifugal Blood Pumps
Authors: Miyazoe Yuki , Sawairi Toshio , Ito Kazuyuki , Konishi Yoshiaki , Yamane Takashi , Nishida Masahiro , Masuzawa Toru , Takiura Koki , Taenaka Yoshiyuki
Published: March 2003

Abstract To establish quantitative, efficient design theories for centrifugal blood pumps, computational fluid dynamics (CFD) analyses were compared to the results of flow visualization tests and hemolysis tests, mainly on the Nikkiso centrifugal blood pump. The results turned out to coincide in the velocity vector plots. CFD analysis revealed that the smaller the gap is, the greater the shear stress becomes. This tendency becomes even greater with a radial gap change. Hemolysis study also indicated that the smaller the gap is, the greater the hemolysis. CFD analysis in comparison with hemolysis tests could be a useful index for developing blood pumps in the future.
Cardiac Surgery and Inhaled Nitric Oxide: Indication and Follow‐up (2–4 Years)
Authors: Yahagi Naoki , Kumon Keiji , Tanigami Hironobu , Watanabe Yasuhiko , Haruna Masaki , Hayashi Hideaki , Imanaka Hideaki , Takeuchi Muneyuki , Takamoto Shinichi
Published: March 2003

We studied the effect of inhaled nitric oxide (NO) on 80 patients who had undergone cardiac surgery in our center. The indications for receiving NO inhalation and the number of patients were as follows: Pp/Ps > 0.5 for pulmonary hypertension (PH) (n = 32; 21 children and 11 adults), severe PH crisis (n = 9), high pulmonary vascular tone (Glenn pressure more than 18 mm Hg after bidirectional Glenn operation) or arterial oxygen saturation (Sa O2) less than 70% despite an Fi
O2 of 1.0 after Blalock‐Taussig shunt (n = 6), mean pulmonary artery pressure (PAP) > 15 mm Hg and transpulmonary gradient (TPG) (mean PAP − left atrial pressure [LAP]) > 8 mm Hg after Fontan‐type operation (n = 18), elevated pulmonary vascular tone (mean PAP > 30 mm Hg and left ventricular assist system [LVAS] flow rate < 2.5 L/min/m2) in patients with LVAS (n = 3), and impaired oxygenation (Pa
O2/Fi
O2 < 100 under positive end‐expiratory pressure [PEEP] > 5 cm H2O) (n = 12). Low dose inhaled NO (10 ppm) had the following effects. In adult PH patients, it significantly reduced the mean PAP (from 37.3 to 27.0 mm Hg; average values are given) and increased the mean systemic arterial pressure (SAP) (64.7 to 75.3 mm Hg). In infant PH patients, it increased the mean SAP (51.8 to 56.1 mm Hg). In patients with a PH crisis, it significantly reduced the central venous pressure (CVP) (13.3 to 8.8 mm Hg) while increasing both the mean SAP (49.4 to 57.9 mm Hg) and Pa
O2/Fi
O2 (135 to 206). In patients after a Fontan‐type operation, it significantly reduced the mean PAP (16.8 to 13.8 mm Hg) and TPG (9.5 to 5.8 mm Hg). In patients under LVAS, it reduced the CVP (11.7 to 8.0 mm Hg) and mean PAP (32.0 to 24.7 mm Hg). In impaired oxygenation patients, Pa
O2/Fi
O2 was increased (75 to 106). Sixty‐five patients were all followed for 2.0–4.3 years (average, 3.1 years). All 65 patients remained free from oxygen requirement, and possible chronic adverse effects including the occurrence of malignant tumors or chronic inflammation in the respiratory tract were not observed.
Antitumor Effect of Cisplatin Incorporated into Polylactic Acid Microcapsules
Authors: Araki  , Tani  , Kodama
Published: March 2003

Cisplatin containing microcapsules (CDDP‐MC) were prepared by encapsulating cisplatin suspended in a dispersing agent in a copolymer (lactic acid) matrix using an in water drying method. Cisplatin release from the microcapsules was controlled by the addition of albumin. The CDDP‐MC were relatively stable in storage, and there was only minimal initial release of the cisplatin from the microcapsules. The antitumor effects of this sustained release dosage form of cisplatin were evaluated in vitro and in vivo in mice. Mice were given an intraperitoneal (i.p.) injection of CDDP‐MC 24 h after inoculation with tumor cells. The CDDP‐MC were effective against Ehrlich ascites tumors and showed reduced acute toxicity compared with standard cisplatin solution. Due to the small initial release of the cisplatin from the microcapsules, however, the antitumor effect of the CDDP‐MC was weaker than that of cisplatin solution. Conventional sustained release preparations have been reported to have large particle sizes and demonstrate large releases of cisplatin from microcapsules. They have been considered more effective than cisplatin solution because of the large initial release of cisplatin from the microcapsules and the maintenance of drug levels. The antitumor effect of our slow‐release formulation of cisplatin was evaluated by administration of CDDP‐MC 1, 4, and 7 days before i.p. implantation of tumor cells. The survival time of the tumor‐bearing mice was prolonged in the CDDP‐MC group, but not in the group treated with cisplatin solution. By using this modified formulation of cisplatin, the toxicity of the drug can be reduced, and effective concentrations of the drug can be maintained locally for prolonged periods of time.
The Pharmacokinetics of Ceftazidime During Hemodiafiltration in Critically Ill Patients
Authors: Sato Toshihide , Okamoto Kazufumi , Kitaura Minoru , Kukita Ichiro , Kikuta Koichi , Hamaguchi Masamichi
Published: March 2003

We studied the pharmacokinetics of ceftazidime in 3 critically ill patients undergoing continuous hemodiafiltration (CHDF). Blood samples were obtained from both the arterial and venous sites of the CHDF system 0, 1, 2, 4, 6, and 12 h after the start of ceftazidime administration. Pharmacokinetic variables were calculated by fitting individual concentration‐time curves to a two‐compartment open model. The elimination phase half‐life was 6.86 h, and the total elimination rate constant was 0.17 h−1. Six hours after the start of administration, the ceftazidime concentration in the arterial site decreased from the peak level of 77.5 ± 31.4 (mean ± standard deviation [SD]) μg/ml to 26.2 ± 2.5 μg/ml. The ceftazidime concentration examined in 2 cases decreased to 14.7 ± 5.8 μg/ml after 12 h. The results suggested that ceftazidime should be administered at 1 g/day in patients with severe infection during CHDF.
The DeBakey Ventricular Assist Device: Current Status in 1997
Authors: Tayama Eiki , Olsen Don B. , Ohashi Yukio , Benkowski Robert , Morley Deborah , Noon George P. , Nosé Yukihiko , DeBakey Michael E.
Published: March 2003

Abstract: In 1993, the development began of a small axial flow blood pump, the DeBakey ventricular assist device (VAD). The material was recently converted to a titanium alloy, and a waterproof pump package was incorporated for long‐term intracorporeal circulation. Thirteen intrathoracic implantations in calves were achieved. Nine animals survived the 2 week perioperative period and were supported for a range of 26–93 days. The first study had low flow due to poor anatomical fit of the straight cannula. In contrast, a curved cannula used subsequently provided a good anatomical fit with sufficient flow. Mean flow of 4.4 L/min was sustained with 9,900 rpm and required power was an average of 8.8 W. No thromboembolic evidences were observed in any case, and the plasma free hemoglobin level was maintained lower than 5 mg/dl, except in the early postoperative period. Three animals were terminated because of bleeding due to anticoagulant mismanagement. Electric interference (n = 1) and drive line breakage/fault (n = 2) were observed as device‐related failures. Minor modifications were made to the drive line. In conclusion, the DeBakey VAD demonstrated adequate basic performance and biocompatibility. The highly reliable mechanical components and improved electrical parts are promising for a long‐term implantable cardiac prosthesis.
System Analysis of the Flow/Pressure Response of Rotodynamic Blood Pumps
Authors: Smith William A. , Goodin Mark , Fu Minghua , Xu Longya
Published: March 2003

Abstract: Design of a rotodynamic blood pumping system to have a suitable, controllable output is a key configuration issue. This study evaluates the benefits of selecting the impeller running specific speed, motor speed‐torque line, and pump operating logic to jointly combine into a suitable characteristic. In this study, a “constant” flow for a given choice of control parameter value was the selected objective. The operating condition selected for analysis was chosen to be typical of an implanted, chronic support pump. Open‐loop operation, fixed torque, fixed power, and fixed power/rpm2 ratio were combined with choices of impeller diameter and speed and motor speed‐torque line. It was found that setting the running specific speed at a higher value than that associated with the best efficiency point resulted in a much more controllable pump. Overall efficiency was only slightly penalized for the model impeller chosen. Power/rpm2 control followed by torque control were most effective. With these control modes, motor characteristics were not critical.
A Preliminary Study of Microcapsule Suspension for Hemolysis Evaluation of Artificial Organs
Authors: Maruyama Osamu , Yamane Takashi , Tsunemoto Naoki , Nishida Masahiro , Tsutsui Tatsuo , Jikuya Tomoaki
Published: March 2003

A microcapsule suspension, a substitute for animal blood in hemolysis tests, has been developed for evaluation of the absolute hemolytic properties of circulatory artificial organs. The microcapsule suspension was made by dispersing microcapsule slurry into an ethylene glycol sodium chloride solution. The microcapsule slurry was composed of a leuco dye solution and polyurethane membrane made by the reaction between aliphatic polyisocyanate and polyamine by interfacial polycondensation. The microcapsule was a small particle containing dye inside. The microcapsule suspension was white; the diameter of the microcapsules was from 5 to 100 μm. The specific gravity of the suspension was 1.024, and the membrane was elastic. The fluid showed Newtonian characteristics, different from animal blood, and its viscosity was approximately 5.8 mPa · s. After the microcapsules were destroyed, the leuco dye was extracted with n‐hexane from the suspension and was measured by spectroscopy after being colored with acid ethanol. Hemolysis can be regarded as a fatigue fracture of cell membranes rather than a static fracture. The destruction of microcapsules by a Potter type tissue grinder was observed at a low stroke number region and was compared to rat blood. Moreover, hemolysis tests of a commercially available centrifugal blood pump and the prototype of our centrifugal pump for mechanism checks were carried out with bovine blood. The hemolysis level of the prototype pump increased with time while the hemolysis level of the commercial blood pump did not change as much as that of the control when both pumps were tested with the microcapsule suspension. These results are similar to tests utilizing bovine blood. Therefore, hemolysis tests of circulatory artificial organs completed with microcapsule suspension are expected to provide results similar to tests with animal blood.