bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Epoetin alfa on Quality of Life in Anemic Cancer Patients
Authors: Cella David , Bron Dominique
Published: March 2003

objectives: The purpose of this paper is to review evidence on the use of Epoetin alfa in the treatment of anemia associated with cancer treatment through a discussion of clinical and quality‐of‐life considerations.

materials and methods: Cancer patients often experience fatigue, which leads to reduced quality of life. There are few effective treatments available to manage this potentially debilitating symptom, which can lead clinicians to become discouraged about treating fatigue. When cancer‐related fatigue is due to anemia, there are viable treatment options. This paper reviews the current management of anemia in cancer patients, with an emphasis on the use of recombinant human erythropoietin (Epoetin alfa).

conclusions: Anemia can contribute to the reduced quality of life experienced by cancer patients. Blood transfusion, the traditional method of treating anemia, is effective and relatively inexpensive, but is associated with certain risks and is subject to limitations in blood supply. Epoetin alfa therapy provides healthcare providers with an effective alternative to blood transfusion, and trial results suggest that this intervention has a positive effect on patients' quality of life. The optimal starting and stopping points for therapy have not yet been determined. In practice, many physicians begin treatment when hemoglobin levels drop below 10 g/dL and stop when they rise above 13 g/dL, with a 75% dose reduction until completion of chemotherapy if hemoglobin again drops below 12 g/dL. Nonresponse (< 1 g/dL rise in hemoglobin) is met with dose increase at 4 weeks and discontinuation after 8 weeks. Controlled studies comparing anemia management via transfusion to the use of Epoetin alfa have not been done to date. Therefore, the relative cost‐effectiveness of Epoetin alfa, an effective but expensive intervention, remains unknown.
Patients' Sensations After Breast Cancer Surgery: A Pilot Study
Authors: Baron Roberta H. , Kelvin Joanne Frankel , Bookbinder Marilyn , Cramer Laura , Borgen Patrick I. , Thaler Howard T.
Published: March 2003

Purpose: The purpose of this study was to obtain information about the prevalence and characteristics of breast sensations after breast cancer surgery, the impact they had on patients, and aggravating and relieving factors.

description of Study: Within 1 month after the date of their surgery, 132 patients with breast cancer completed an instrument rating the prevalence, severity, and level of distress of breast sensations. Information also was obtained on the impact that those sensations had on activities of daily living and factors that triggered and provided relief from sensations.

Results: Certain sensations remain prevalent (numb, tender), severe (burning, sharp), and distressing (cramping, painful). Overall these sensations significantly interfered with patients' activities of daily living. Certain activities (movement, position change) triggered sensations, while others (position change, medication) provided relief.

clinical Implications: Healthcare professionals can use the information learned from this pilot study to educate patients both preoperatively and postoperatively about prevalent breast sensations after surgery for breast cancer and about the types of activities that may aggravate or relieve these sensations. As patient educators and advocates, oncology professionals must continue to explore the long‐term effects and treatment options to provide optimal care and support to patients who have or are likely to have postsurgical breast sensations. More studies are needed to explore long‐term effects and treatment options.
Clinical Trial Enrollment of Rural Patients with Cancer
Authors: Paskett Electra D. , Cooper M. Robert , Stark Nancy , Ricketts Thomas C. , Tropman Sara , Hatzell Teresa , Aldrich Tim , Atkins James
Published: March 2003

purpose: The goal of this study was to examine the effect of a rural community clinical oncology program‐based cancer‐care intervention program that was launched to increase the number of rural patients with cancer enrolled in clinical trials.

description of study: Five rural counties in eastern North Carolina served as intervention communities, and five rural counties in South Carolina served as the comparison region. The intervention counties used a rapid tumor‐reporting system, a nurse facilitator who identified and prompted oncologists to enter patients into clinical trials, a quarterly newsletter to primary‐care physicians about cancer treatment and clinical trials, and a health educator who focused on community‐wide education regarding cancer prevention, treatment, and clinical trial information. Outcomes included changes in knowledge and attitudes about clinical trials among the primary‐care providers who were surveyed and enrollment in clinical treatment trials for breast and colorectal cancer, as analyzed by comparing practice pattern data from before and after the intervention.

results: The results indicate that the intervention was not effective. The proportion of primary‐care physicians who were aware of clinical trials for their patients with cancer rose slightly in comparison counties (26% to 34%) but remained constant (41% to 43%) in intervention counties. Perceived patient and actual physician barriers toward clinical trial participation were reported by the physicians. A minority of potentially eligible patients with breast or colon cancer in both North Carolina and South Carolina were enrolled in clinical trials.

clinical implications: These data suggest that different types of interventions may be needed to improve accrual to cancer treatment trials in rural communities. In addition, the role that primary‐care providers play in encouraging patients with cancer to participate in clinical treatment trials needs further exploration.
Developmental constraints on the mode of reproduction in the facultatively parthenogenetic cockroachNauphoeta cinerea
Authors: Corley Laura S. , Blankenship Jill R. , Moore Allen J. , Moore Patricia J.
Published: March 2003

Considerable work in evolutionary biology has focused on the question of why sex persists. Both advantages to sex and constraints limiting a return to asexual reproduction are hypothesized to maintain sex once it evolves. Developmental constraints would limit asexual reproduction from a sexual species if it were difficult for females to switch from making eggs that do not develop without fertilization to making zygotes that are capable of developing in the absence of fertilization.Nauphoeta cinereais an ovoviviparous cockroach in which some females are capable of switching from a sexual mode of reproduction to an asexual mode when isolated from males. Yet, while facultative parthenogenesis can occur in individuals, few females make the switch. Thus, this cockroach provides an ideal system for examining the potential role of developmental constraints in maintaining sex. Here we compare the cytogenetics and embryonic development of sexual and parthenogenetic offspring inN. cinerea.We find that deviations from normal ploidy levels are associated with abnormal development. All viableN. cinereaembryos exhibit typically hemimetabolous insect embryogenesis. Although there is no variation among embryos in development within a sexually produced clutch, we see extreme variation in asexually derived clutches. These results suggest that developmental constraints limit the success of asexual reproduction in this facultatively parthenogenetic cockroach. Our data further suggest that the specific constraint occurs in the switch from a meiotic mode of reproduction requiring fertilization to diploid zygotes that develop in the absence of fertilization.
The stability of thoracic segmentation in trilobites: a case study in developmental and ecological constraints
Authors: Hughes Nigel C. , Chapman Ralph E. , Adrain Jonathan M.
Published: March 2003

The decline in origination rate of new metazoan body plans following the Cambrian radiation has been suggested to reflect developmental canalization in derived taxa, limiting their ability to evolve forms with radically different morphotypes. Segmentation is a fundamental aspect of arthropod body plan, and here we show that a derived trilobite that secondarily converged on a morphotype characteristic of basal members of the clade also reverted to a pattern of segmental variability common among basal trilobites. Hence a secular trend in loss of variability of the trilobite thorax was not due to the evolution of an inviolable developmental constraint. This result challenges the notion of developmental canalization in phylogenetically derived taxa. Rather, early variability in trilobites may be the result of ecological factors that promoted segment‐rich thoracic morphotypes during Cambrian time.
Ancient origins of axial patterning genes: Hox genes and ParaHox genes in the Cnidaria
Authors: Finnerty John R. , Martindale Mark Q.
Published: March 2003

Among the bilaterally symmetrical, triploblastic animals (the Bilateria), a conserved set of developmental regulatory genes are known to function in patterning the anterior–posterior (AP) axis. This set includes the well‐studied Hox cluster genes, and the recently described genes of the ParaHox cluster, which is believed to be the evolutionary sister of the Hox cluster (Brooke et al. 1998). The conserved role of these axial patterning genes in animals as diverse as frogs and flies is believed to reflect an underlying homology (i.e., all bilaterians derive from a common ancestor which possessed an AP axis and the developmental mechanisms responsible for patterning the axis). However, the origin and early evolution of Hox genes and ParaHox genes remain obscure. Repeated attempts have been made to reconstruct the early evolution of Hox genes by analyzing data from the triphoblastic animals, the Bilateria (Schubert et al. 1993; Zhang and Nei 1996). A more precise dating of Hox origins has been elusive due to a lack of sufficient information from outgroup taxa such as the phylum Cnidaria (corals, hydras, jellyfishes, and sea anemones). In combination with outgroup taxa, another potential source of information about Hox origins is outgroup genes (e.g., the genes of the ParaHox cluster). In this article, we present cDNA sequences of two Hox‐like genes (anthox2 and anthox6 ) from the sea anemone, Nematostella vectensis. Phylogenetic analysis indicates that anthox2 (=Cnox2) is homologous to the GSX class of ParaHox genes, and anthox6 is homologous to the anterior class of Hox genes. Therefore, the origin of Hox genes and ParaHox genes occurred prior to the evolutionary split between the Cnidaria and the Bilateria and predated the evolution of the anterior–posterior axis of bilaterian animals. Our analysis also suggests that the central Hox class was invented in the bilaterian lineage, subsequent to their split from the Cnidaria.
Limbs and tail as evolutionarily diverging duplicates of the main body axis
Authors: Minelli Alessandro
Published: March 2003

SUMMARY Contrasting hypotheses have been proposed to explain the pervasive parallels in the patterning of arthropod and vertebrate appendages. These hypotheses either call for a common ancestor already provided with patterned appendages or body outgrowths, or for the recruitment in limb patterning of single genes or genetic cassettes originally used for purposes other than axis patterning. I suggest instead that body appendages such as arthropod and vertebrate limbs and chordate tails are evolutionarily divergent duplicates (paramorphs) of the main body axis, that is, its duplicates, albeit devoid of endodermal component. Thus, vertebrate limbs and arthropod limbs are not historical homologs, but homoplastic features only transitively related to real historical homologs. Thus, the main body axis and the axis of the appendages have distinct but not independent evolutionary histories and may be involved in processes of homeotic co‐option producing effects of morphological assimilation. For instance, chordate segmentation may have originated in the posterior appendage (tail) and subsequently extended to the trunk.
Otx1gene‐controlled morphogenesis of the horizontal semicircular canal and the origin of the gnathostome characteristics
Authors: Mazan Sylvie , Jaillard Danielle , Baratte Blandine , Janvier Philippe
Published: March 2003

SUMMARYThe horizontal semicircular canal of the inner ear is a unique feature of gnathostomes and is predated by the two vertical semicircular canals, which are already present in lampreys and some fossil, armored jawless vertebrates regarded as close relatives of gnathostomes. Inactivation in mice of theorthodenticle‐related geneOtx1results in the absence of this structure. In bony fishes and tetrapods (osteichthyans), this gene belongs to a small multigene family comprising at least two orthology classes,Otx1andOtx2. We report that, as in the mouse, xenopus and zebrafish,Otx1‐andOtx2‐related genes are present in a chondrichthyan, the dogfishScyliorhinus canicula, with anOtx1expression domain in the otocyst very similar to those observed in osteichthyans. A strong correlation is thus observed in extant vertebrates between the distribution of the horizontal semicircular canal and the presence of anOtx1ortholog expressed in the inner ear, which supports the hypothesis that the absence of this characteristic inOtx1‐/‐mice may correspond to an atavism. The same conclusion applies to two other gnathostome‐specific characteristics also deleted inOtx1‐/‐mice, the utriculosaccular duct and the ciliary process. Together with functional analyses ofOtx1andOtx2genes in mice and comparative analyses of theOtxgene families characterized in chordates, these discoveries lead to the hypothesis that some of the anatomic characteristics of gnathostomes have appeared quite suddenly and almost simultaneously in vertebrate evolution, possibly as a consequence of gene functional diversifications following duplications of an ancestral chordate gene.
The amphioxus Hox cluster: deuterostome posterior flexibility andHox14
Authors: Ferrier David E. K. , Minguillón Carolina , Holland Peter W. H. , Garcia‐Fernàndez Jordi
Published: March 2003

SUMMARYThe amphioxus (Branchiostoma floridae) Hox cluster is a model for the ancestral vertebrate cluster, prior to the hypothesized genome‐wide duplications that may have facilitated the evolution of the vertebrate body plan. Here we describe the posterior (5′) genes of the amphioxus cluster, and report the isolation of four new homeobox genes. Vertebrates possess 13 types of Hox gene (paralogy groups), but we show that amphioxus possesses more than 13 Hox genes. Amphioxus is now the first animal in which a Hox14 gene has been found. Our mapping and phylogenetic analysis of amphioxus “Posterior Class” Hox genes reveals that these genes are evolving at a faster rate in deuterostomes than in protostomes, a phenomenon we term Posterior Flexibility.
Modularity, evolvability, and adaptive radiations: a comparison of the hemi‐ and holometabolous insects
Authors: Yang Andrew S.
Published: March 2003

SUMMARY Despite recent attention given to the concept of modularity and its potential contribution to the evolvability of organisms, there has been little mention of how such a contribution may affect rates of diversification or how this would be assessed. A first key prediction is that lineages with relatively greater degrees of modularity in given traits should exhibit higher rates of diversification. Four general conditions for testing this prediction of the modular evolvability hypothesis are outlined here. The potential role of modularity as a deterministic factor in adaptive radiations is best examined by looking at historic patterns of diversification rather than just levels of extant diversity, the focus of most analyses of key innovations.

Recent developmental evidence supports the notion that phenotypes of juvenile and adult stages of insects with “complete” metamorphosis (Holometabola) are distinct developmental and evolvable modules compared to the highly correlated life stages of insects with “incomplete” metamorphosis (Hemimetabola). Family‐level rates of diversification for these two groups were calculated from the fossil record. The Holometabola was found to have a significantly and characteristically higher rate of diversification compared to the less modular Hemimetabola, consistent with the idea that intrinsic differences in modularity can influence the long‐term evolvability of organisms.

The modular evolvability hypothesis also makes a second key prediction: that characters in more modular clades will exhibit greater levels of variation due to their independence. This provides an independent, phenotypically based test of the hypothesis. We discuss here how this second prediction may be tested in the case of the Hemi‐ and Holometabola.
Multiple origins of a major novelty: moveable abdominal lobes in male sepsid flies (Diptera: epsidae), and the question of developmental constraints
Authors: Eberhard William G.
Published: March 2003

SUMMARY Contrary to the impression given by their extreme scarcity among extant species of flies, moveable processes on the abdomen are apparently of relatively simple developmental origin, and they have evolved multiple times in males of the small family Sepsidae. They are used to stimulate the female during copulation in two groups, where they are probably independently derived. Because female cuing of reproductive decisions on particular types of stimuli will tend to favor male abilities to elaborate such stimuli, sexual selection by female choice may sometimes result in sustained selection for certain types of innovations in males. The lack of moveable appendages in most dipterans may be due not to developmental constraints, but to lack of selective advantages.
Life history evolution and comparative developmental biology of echinoderms
Authors: Hart Michael W.
Published: March 2003

SUMMARY Evolutionary biologists studying life history variation have used echinoderms in experimental, laboratory, and field studies of life history evolution. This focus on echinoderms grew originally from the tradition of comparative embryology, in which echinoderms were central. The tools for obtaining and manipulating echinoderm gametes and larvae were taken directly from comparative embryological research. In addition, the comparative embryologists employed a diverse array of echinoderms, not a few model species, and this diversity has led to a broad understanding of the development, function, and evolution of echinoderm larvae. As a result, this branch of life history evolution has deep roots in comparative developmental biology of echinoderms. Here two main aspects of this relationship are reviewed. The first is a broad range of studies of fertilization biology, dispersal, population genetics, functional morphology, and asexual reproduction in which developmental biologists might take a keen interest because of the historical origins of this research in echinoderm comparative embryology. The second is a similarly broad variety of topics in life history research in which evolutionary biologists require techniques or data from developmental biology in order to make progress on understanding patterns of life history variation among echinoderm species and higher taxa. Both sets of topics provide opportunities for interaction and collaboration.
Evolution of male sexual characters in the Oriental Drosophila melanogaster species group
Authors: Kopp Artyom , True John R.
Published: March 2003

SUMMARY Understanding the genetic and molecular mechanisms of morphological evolution is one of the greatest challenges in evolutionary biology. Sexually dimorphic traits, which often evolve at a high rate due to their involvement in mate choice and sexual selection, present unique opportunities for investigating changes in development over short evolutionary distances. Phylogenetic analysis is essential to provide a historical framework for comparative studies of development by establishing the order and polarity of morphological changes. In this report, we apply a new molecular phylogeny to reconstruct the evolution of male sexual characters in a group of species closely related to the model species Drosophila melanogaster. These highly variable traits include wing melanin patterns, the sex comb, and the structure of external genitalia and analia. We show that sexually dimorphic characters can diverge very rapidly among closely related species. More surprisingly, we also find a pervasive pattern of independent origin and secondary loss of male sexual traits in different evolutionary lineages.
Fins to limbs: what the fossils say1
Authors: Coates Michael I. , Jeffery Jonathan E. , Ruta Marcello
Published: March 2003

SUMMARY A broad phylogenetic review of fins, limbs, and girdles throughout the stem and base of the crown group is needed to get a comprehensive idea of transformations unique to the assembly of the tetrapod limb ground plan. In the lower part of the tetrapod stem, character state changes at the pectoral level dominate; comparable pelvic level data are limited. In more crownward taxa, pelvic level changes dominate and repeatedly precede similar changes at pectoral level. Concerted change at both levels appears to be the exception rather than the rule. These patterns of change are explored by using alternative treatments of data in phylogenetic analyses. Results highlight a large data gap in the stem group preceding the first appearance of limbs with digits. It is also noted that the record of morphological diversity among stem tetrapods is somewhat worse than that of basal crown group tetrapods. The pre‐limbed evolution of stem tetrapod paired fins is marked by a gradual reduction in axial segment numbers (mesomeres); pectoral fins of the sister group to limbed tetrapods include only three. This reduction in segment number is accompanied by increased regional specialization, and these changes are discussed with reference to the phylogenetic distribution of characteristics of the stylopod, zeugopod, and autopod.
Sexual dimorphism in gender plasticity and its consequences for breeding system evolution
Authors: Delph Lynda F.
Published: March 2003

SUMMARYFlowering plants are able to develop gametes throughout their lives. As a consequence, environmental conditions can impact this development and alter a plant's functional gender or the degree to which it achieves fitness through male or female function. Two dimorphic breeding systems are widespread among angiosperm families: gynodioecy (hermaphrodites and females) and dioecy (males and females). Gynodioecy can evolve into dioecy, via loss of female function on the hermaphrodites, or it can remain stable. Here I discuss how developmental plasticity of gender can impact the sex ratio of populations and thereby influence the transition of one breeding system into another. I review studies showing that greater plasticity of fruit production by hermaphrodites as compared with females causes sex ratios among populations to vary in response to environmental conditions, with higher female frequency expected in harsh or low‐quality sites. I also review how dioecy may evolve in dry sites to avoid inbreeding and any consequent inbreeding depression. Taken together, these studies show the importance of understanding how ecological development affects functional gender and consequently the evolutionary stability or malleability of dimorphic breeding systems.
Developmental flexibility and the effect of social environment on fertility and fecundity in parthenogenetic reproduction
Authors: Moore Patricia J. , Moore Allen J.
Published: March 2003

SUMMARYOne specialized environment that can influence development arises in the context of social interactions, including the environment contributed by a sexual partner during sexual reproduction. It is often difficult, however, to separate out the effect of mating (fertilization) from the effect of social environment. In the study reported here we examine the effect of social environment mediated by a pheromonal signal on the fertility and fecundity of the facultatively parthenogenetic cockroachNauphoeta cinerea.By examining parthenogenetically reproducing females, we isolate the effects of social environment in the absence of mating or fertilization. Females exposed to male odors are more likely to produce parthenogenetic offspring. Further, increased exposure to the male pheromone increases the number of offspring produced. Variation in timing of reproduction is also dependent on the male. Thus, social environments are a mechanism by which males contribute to the development of their offspring, resulting in variation in development. This study illustrates the potential evolutionary importance of social environments in development, because a requirement for male‐contributed environments may be a constraint to evolving asexual reproduction from a sexually reproducing species.
It is the goal of this section to publish material that provides information regarding specific issues, aspects of artificial organ application, approach, philospphy, suggestions, and/or thoughts for the future.
Authors: Eiswirth Georg , Walch Stefan , Bommer Jürgen
Published: March 2003

Heparin therapy in patients can be monitored bedside during dialysis treatment by activated partial thromboplastin time (APTT) measurements using portable coagulation monitors. We verified the efficacy of the CoaguChek Plus System (Boehringer Mannheim, GmbH, Mannheim, Germany) for this purpose. The first series of results was obtained using CoaguChek Plus APTT controls (Level 1 and Level 2) on 3 instruments. The coefficients of variation (CVs) were found to be in the range of 3.6 to 5.0% based on results per instrument (n = 20) and per control level (n = 60). The second series of results was obtained using whole blood drawn from the arterial lines of patients during dialysis treatment. Three determinations out of 1 ml of fresh whole blood gave an overall mean CV of 4.9% from the 123 samples tested. Samples were taken before the onset of heparin treatment, 2 h after treatment was started, and at the end of treatment. The CoaguChek Plus APTT measurements were compared to measurements made using laboratory routine method STA APTT (Boehringer Mannheim GmbH) with results from 104 whole blood samples. Regression analysis according to Passing and Bablok showed good correlation (r = 0.885) and good agreement (y = 0.997x− 6.6) between both methods. Ease of use, excellent performance, reliability, and rapid availability of results within 3 min make the CoaguChek Plus APTT measurements suitable for monitoring patients during dialysis.
Activity of Free Radical Scavenging Enzymes in Red Cells and Plasma of Patients Undergoing Extracorporeal Low‐Density Lipoprotein Apheresis
Authors: Schettler Volker , Wieland Eberhard , Methe Heiko , Schuff‐Werner Peter , Oellerich Michael , Müller Gerhard Anton
Published: March 2003

There is evidence that reactive oxygen species (ROSs) are generated in extracorporeal circuits. Free radical scavenging enzymes (FRSEs) such as glutathione reductase (GSSG‐R), glutathione peroxidase (GSH‐Px), and superoxide dismutase (SOD) protect against the damaging effect of ROSs. The influence of extracorporeal treatment on FRSE activity was investigated in the plasma and red blood cells (RBCs) of 21 patients undergoing regular low‐density lipoprotein (LDL) apheresis. The FRSEs GSSG‐R, GSH‐Px, and SOD were measured. Determinations were made before and after a single treatment. Because all apheresis patients suffered from coronary heart disease (CHD), 201 CHD patients and 90 individuals without CHD, neither group undergoing apheresis, served as controls. In apheresis patients, GSH‐Px (33.9 ± 8.2 U/g Hb) and GSSG‐R (7.6 ± 0.9 U/g Hb) activities were increased whereas SOD activity (5.4 ± 1.5 U/g Hb) was decreased in RBCs before a single treatment compared to controls. Plasma FRSEs of apheresis patients were not different from those of controls. There was no effect of a single treatment on FRSEs in RBCs. However, a significant decrease in plasma GSH‐Px activity (209.9 ± 24.9 U/ml) due to the extracorporeal treatment was observed. These data show that long‐term extracorporeal therapy with LDL apheresis modulates the activity of antioxidant enzymes in RBCs whereas a single treatment was without major effect on FRSE activity in RBCs and plasma, except for plasma GSH‐Px.
β2‐Microglobulin and Low‐Flux SyntheticDialyzers
Authors: Klinkmann Horst , Buscaroli Andrea , Stefoni Sergio
Published: March 2003

Abstract: The aim of this study was to compare the effect on β2‐microglobulin (β2‐M) plasma levels of dialyzers with 3 low‐flux synthetic membranes and regenerated cellulose (Cuprophan) in 12 chronic dialysis patients. The synthetic membrane materials chosen were low‐flux polymethylmethacrylate (PMMA), low‐flux polysulfone (PS 400), and polycarbonate‐polyether (Gambrane). Adequate and comparable removal of small solutes was provided by dialyzers with all 4 membrane materials used under similar conditions. A significant reduction of β2‐M plasma levels was seen only with Gambrane while the other 2 synthetic membrane materials gave rise to increases similar to those known to occur with Cuprophan. After correction for the hemoconcentration caused by ultrafiltration, dialysis with Gambrane showed a 24% lower plasma β2‐M level while the β2‐M concentrations with the other 3 membrane materials were practically unchanged. In addition, the efficiency of Gambrane dialyzers in β2‐M removal was able to significantly lower the predialysis plasma β2‐M levels after only 5 dialysis sessions. The hemocompatibility of the 3 synthetic low‐flux membranes as judged by the white blood cell (WBC) count and complement activation was similar and therefore cannot be used to explain the different β2‐M plasma levels. In anticipation of gaining further insight into the mechanisms of accumulation and deposition of β2‐M in dialysis patients, a worthwhile approach may be to use a low‐flux membrane such as Gambrane which combines removal with protection against potential activating factors in the dialysis fluid.
Availability and Limits of Intermediate Cardiovascular Technology
Authors: Puruhito
Published: March 2003

Cardiovascular technology has been applied in the treatment of various diseases in Indonesia since its development in the late 1970s. Medical experts who have completed their training abroad began to implement their knowledge in cardiovascular service while a multifactorial limitation occurred in the country. The major limiting factor is still the country's infrastructure, which should support the treatment measures in modern cardiovascular technology. Other limiting factors concern nonmedical subjects, e.g., ethics, beliefs, religion, and the financial and basic organization of organ transplantation. Organ replacement started with artificial kidney/hemodialysis in the late 1970s, and was successfully carried out together with the further commencement of living related donor renal transplantation. Development of cardiac surgery with extracorporeal circulation gave rise to the stimulation of animal trials of cardiac transplant, pancreas transplant, and other subsets of organ transplantation. With the increasing modus of modernization, major hospitals in 3 large cities have shown increasing needs for organ transplant, and, parallel to that, the increasing number of potential organ donors, the cause of death dominated by brain death resulting from traffic accidents. The emerging need for liver and cardiopulmonary transplants has also been observed during the last 5 years, despite the improvement of general health care. However, similar to many Asian countries, because of religious and cultural considerations, it may be difficult to find donors whose relatives are willing to donate organs from their deceased relatives, especially for heart, lung, liver, and pancreas transplants. Alternative methods for artificial organs should receive more emphasis. We present the activities which have been established so far and how we should cope with the question of how present technology brings answers to the needs of organ transplant and artificial organs. Some innovative steps that we have made will be outlined.
Effect of a Balanced Biventricular Bypass System on Left Ventricular Energies
Authors: Kodera Kohjiro , Kitamura Masaya , Shibuya Mitsuhiro , Kurihara Hisao , Koyanagi Hitoshi
Published: March 2003

Left dominant biventricular failure is a common type of heart failure after cardiac surgery. We developed a biventricular bypass (BVB) system for treatment of postcardiotomy ventricular failure, and we previously reported that the clinical results of the BVB system were superior to those obtained with venoarterial bypass (VAB). The purpose of this study was to evaluate the effect of the BVB system on left ventricular (LV) performance in comparison to that of VAB by means of the LV pressure‐volume relationship (PVR). Eight adult mongrel dogs (14–21 kg) underwent VAB with right atrial and aortic cannulation. Left atrial cannulation was added for BVB, and both atrial drainage tubes were joined with a Y‐shaped connector. The bypass flow was maintained at half of the baseline cardiac output (0.7–1.0 L/min), and the hemodynamic parameters were monitored. A high fidelity microtip catheter and a conductance catheter were used to evaluate LV function. The slope of the LV end‐systolic pressure‐volume relation (Emax), the slope of the LV end‐systolic pressure‐stroke‐volume relation (Ea), the LV stroke work (SW), LV potential energy (PE), LV pressure‐volume area (PVA), the slope of the SW end‐diastolic volume relation (PRSW), and an index of the LV energizing charge (ratio of PE/PVA) were assessed during transient occlusion of the inferior vena cava. LV contractility (Emax) showed no significant change during each experiment. Standardized LV work (PRSW) was reduced by BVB in comparison to the baseline and in comparison to VAB. The rate of LV energy charge (PE/PVA) significantly increased only during BVB. These results suggested that the BVB system might be an effective circulatory support for reducing LV work and improving the LV energizing charge in patients with severe heart failure after cardiac operation.
In Vivo Evaluation of the Miniaturized Gyro Centrifugal Pump as an Implantable Ventricular Assist Device
Authors: Takami Yoshiyuki , Otsuka Goro , Mueller Jurgen , Sugita Yohichi , Nakata Kin‐ichi , Tayama Eiki , Ohashi Yukio , Schima Heinrich , Schmallegger Helmut , Wolner Ernst , Nosé Yukihiko
Published: March 2003

A miniaturized Gyro centrifugal pump has been developed to be incorporated into a totally implantable artificial heart. The Gyro PI (permanently implantable) model is a pivot bearing supported centrifugal pump with a priming volume of 20 ml. With the miniaturized actuator, the pump‐actuator package has a height of 53 mm, a diameter of 65 mm, and a displacement volume of 145 ml. To evaluate the hemocompatibility and efficiency of the Gyro PI pump system, a plastic prototype (Gyro PI‐601) was implanted into a bovine model as a left or right ventricular assist device (LVAD or RVAD), bypassing from the left ventricular apex to the descending aorta or from the right ventricular infundibulum to the main pulmonary artery. The calves were anticoagulated with heparin to maintain activated clotting times from 150 to 200 s. Four calves were supported for 23, 24, and 50 days in the LVAD studies, and 40 days in the RVAD study. The first calf died due to intrathoracic bleeding associated with sepsis. The second calf was euthanized for a low flow rate less than 2 L/min due to an obstructed inflow with growing pannus. The third and fourth calves were euthanized as scheduled. Renal and hepatic functions remained normal, and plasma free hemoglobin values were less than 8 mg/dL throughout the experiments. The fourth case showed flow rates of 4.83 ± 0.57 L/min, and input power of 6.16 ± 0.49 W, and the inside temperature of the actuator of 43.5 ± 0.52°C. The pumps implanted in the fourth calf demonstrated no thrombus formation at the autopsy. These in vivo experiments revealed that the Gyro PI pump can provide adequate flow as an easily implantable, efficient, antithrombogenic, and nonhemolytic centrifugal LVAD or RVAD with miniaturized actuators.
Enhanced Fluid Removal Guided by Blood Volume Monitoring During Chronic Hemodialysis
Authors: Steuer Robert R. , Germain Michael J. , Leypoldt John K. , Cheung Alfred K.
Published: March 2003

Fluid overload predisposes chronic hemodialysis patients to cardiovascular disease, a significant cause of morbidity and mortality in these patients. We evaluated the efficacy of monitoring changes in blood volume during routine hemodialysis to detect fluid overload. Intradialytic changes in blood volume were monitored by continuously measuring hematocrit in all 56 patients in a single dialysis unit over 7 weeks. After Week 1, patients were categorized into 2 separate groups depending on their maximum intradialytic decreases in blood volume. In Group 1, 46 of 56 or 82% had greater than a 5% decrease in blood volume while in Group 2, 10 of 56 or 18% had less than a 5% decrease in blood volume. During Weeks 2–7, dialytic fluid removal was intentionally increased in Group 2 patients by 0.80 ± 0.62 L (mean ± SD) or 47 ± 43%. This intervention resulted in a larger (p < 0.02) intradialytic decrease in body weight (2.7 ± 0.9 kg versus 2.0 ± 0.8 kg) and a larger (p < 0.02) intradialytic decrease in blood volume (15 ± 5% versus 4 ± 1%) than experienced during Week 1 with a low incidence of symptoms. We conclude that there is a significant percentage of chronic hemodialysis patients who can tolerate additional fluid removal without hypovolemic symptoms even though they are considered to be at dry weight by routine physical examination and that the identification of these patients can be facilitated by intradialytic blood volume monitoring.
Platelet Protective Effect of TAK‐029, A Novel Glycoprotein IIb/IIIa Antagonist: An In Vitro Study
Authors: Kawahito Koji , Fujimura Akio , Kobayashi Eiji , Misawa Yoshio , Fuse Katsuo
Published: March 2003

Previous studies have indicated that exposure of fibrinogen receptors associated with the glycoprotein IIb/IIIa complex contributes to platelet loss during cardiopulmonary bypass. TAK‐029 is a newly developed reversible, nonpeptide inhibitor of platelet glycoprotein IIb/IIIa receptors. In this study, we tested the platelet preserving effect of TAK‐029 in an in vitro model. The methods included the comparison of the release of β‐thromboglobulin (β‐TG) between a TAK‐029 group (n = 5) and a control group (n = 5) in a mock circulation under a shear force generated by a centrifugal pump. To evaluate the degree of β‐TG release, Δβ‐TG/ΔT was calculated where Δβ‐TG is the increase in βTG and ΔT is the time. The results showed that the value of Δβ‐TG/ΔT in the TAK‐029 group was significantly lower than it was in the control group (4.22 ± 0.27 × 102 ng/ml vs. 7.33 ± 0.66 × 102 ng/ml, respectively). In conclusion, TAK‐029 reduced the platelet activation under the shear forces of an in vitro model, suggesting that TAK‐029 is a potential candidate for platelet protection during cardiopulmonary bypass.
Icodextrin Provides Long Dwell Peritoneal Dialysis and Maintenance of Intraperitoneal Volume
Authors: Peers Elizabeth , Gokal Ram
Published: March 2003

Icodextrin 7.5% is an isosmolar solution for once‐daily use in peritoneal dialysis for patients with end‐stage renal failure (ESRF). It produces substantial ultrafiltration (UF), performing best over longer dwells of 8–12 h in continuous ambulatory peritoneal dialysis (CAPD) patients, and up to 16 h in automated peritoneal dialysis (APD) patients. Subsequent use in other clinical areas (ultrafiltration failure) and normal postmarketing clinical experience has established its tolerability and safety profiles; a small number of patients, including those with diabetes, have now received icodextrin for up to 6 years. Icodextrin's ability to maintain intraperitoneal volume over many hours has led to its undergoing development as an intraperitoneal drug delivery system for targeted regional delivery of anticancer drugs and lymphatic delivery of anti‐HIV treatment. Isosmolar icodextrin 7.5% solution represents the first major advance in the treatment of ESRF by peritoneal dialysis since the development of CAPD using glucose‐based solutions 20 years ago.
Is Ionic Dialysance a Valid Parameter for Quantification of Dialysis Efficiency?
Authors: Mercadal  , Petitclerc  , Jaudon  , Béné  , Goux  , Jacobs
Published: March 2003

The on‐line measurement during hemodialysis of ionic dialysance provides an estimation of urea clearance with a good and already proven correlation. Some discrepancies remain controversial, and the influence of the dialyzer membrane is still being debated. Eighty‐eight measurements of ionic dialysance (ID) were performed with a Diascan module (Hospal R&D, Int., Lyon, France), 51 with cellulosic membranes, and 37 with synthetic membranes, chosen according to their surface charges. The ID was compared to the urea clearance (UK) measured from the blood (n = 16) and dialysate (n = 88) sides. The ID is closely correlated (r = 0.91) but significantly (p < 0.01) lower than the UK by 5% (ID/UK = 0.95 ± 0.06). The correlation is improved by a semilogarithmic regression analysis (r = 0.93). Regarding the influence of the membrane charge, a slight difference is only evidenced for UK < 180 ml/min whereby ID is closer to the urea clearance for the charged membranes (ID/UK = 0.98 ± 0.05 for charged membranes versus 0.95 ± 0.05 for noncharged membranes, p < 0.05). The discrepancy between ID and UK could be related with the difference in the blood distribution volume of urea and that of electrolytes. The good correlation provides the major argument for ID being used as a monitoring parameter of the delivered dialysis dose. Having integrated the discrepancy between ID and UK, prescription can be guided by ID for delivering the adequate normalized dialysis dose as defined by Kt/V.
Adsorption of Complement, Cytokines, and Proteins by Different Dialysis Membrane Materials: Evaluation by Confocal Laser Scanning Fluorescence Microscopy
Authors: Fujimori Akira , Naito Hidemune , Miyazaki Tetsuo
Published: March 2003

The membranes tested in the present study were cellulose triacetate (CTA), polymethylmethacrylate (PMMA), and polyacrylonitrile (PAN). The adsorption by each membrane of albumin, IgG, C3a, interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), human neutrophil elastase (HNE), and tumor necrosis factor α (TNFα) was examined and semiquantitatively graded by confocal laser scanning fluorescence microscopy (CLSFM). After clinical use the dialyzers were treated with antibodies for these proteins and cytokines. Then the samples were incubated with fluorescein isothiocyanate‐labeled anti‐IgG antibody and observed by CLSFM. The changes in the blood levels of C3a and cytokines were also studied. In the CTA membrane, the adsorption of these substances, except for albumin and HNE, was less than in the synthetic membranes. The PAN membrane revealed the most abundant adsorption, especially for IL‐1β, IL‐6, and TNFα. Although a marked elevation of C3a in the blood was observed in the CTA membrane, considerable adsorption was evident in the PMMA and the PAN membranes. Because the changes in the blood levels could be affected by membrane adsorption, both the blood levels and the adsorption of the biocompatibility parameters should be evaluated when membrane biocompatibility is discussed.
Design and Development Strategy for the Rotary Blood Pump
Authors: Nosé Yukihiko
Published: March 2003

Development of an antitraumatic antithrombogenic and durable blood pump is a very difficult task. Based upon this author's experience of over 35 years in the development of various types of cardiac prostheses, development strategies for a rotary blood pump are described. A step‐by‐step development strategy is thus proposed. Initially, the development of a 2 day antitraumatic pump (Phase 1) would be made. Then, conversion of this pump to a 2 week antithrombogenic pump (Phase 2) should be attempted. After the successful development of the Phase 2 pump, the conversion of this device to a durable, implantable, and long‐term blood pump (Phase 3) should be established. Based upon this development strategy, 2 rotary blood pumps, namely, the axial flow blood pump and the centrifugal blood pump, have been developed in less than 6 years with modest development costs.
Role of Calcium Carbonate Administration Timing in Relation to Food Intake on Its Efficiency in Controlling Hyperphosphatemia in Patients on Maintenance Dialysis
Authors: Sechet A. , Hardy P. , Hottelart C. , Rasombololona M. , Abighanem O. , Oualim Z. , Brazier M. , Achard J.‐M. , Pruna A. , Moriniere P. , Fournier A.
Published: March 2003

Abstract: A study has claimed that at an equal elemental calcium dose, CaCO3 was not less but equally as efficient in controlling predialysis hyperphosphatemia as calcium acetate, provided both calcium salts were ingested 5 min before meals instead of during meals because the higher acidity of the fasting gastric juice would allow for better dissociation of CaCO3. However, this study did not directly demonstrate that the efficiency of CaCO3 in controlling hyperphosphatemia was actually greater when it was administered before a meal than during a meal. To examine this point, we performed a 3 month randomized crossover trial in 12 reliable and stable patients maintained on chronic hemodialysis. Their plasma concentrations of calcium, protein, phosphate, bicarbonate, urea, and creatinine were measured before the first dialysis of each week and the amount of intact parathyroid hormone (PTH) at the beginning and at the end of each of the 3 months. Comparison of the plasma concentrations measured during the 2 modes of administration showed no significant differences in creatinine, urea, bicarbonate, or intact PTH. The mean (±SD) plasma concentration of PO4 was not significantly lower (1.88 ± 0.50 vs. 1.74 ± 0.41 mM) whereas the corrected level of plasma Ca was significantly lower (2.30 ± 0.17 vs. 2.38 ± 0.16 mM; p < 0.04) when CaCO3 was given before meals than during meals. In conclusion, the administration of CaCO3 before a meal does not increase its efficiency in controlling hyperphosphatemia because the level of plasma PO4 was actually slightly higher with this timing of administration whereas the comparison of the creatinine and urea levels suggested a stability of phosphate intake and the comparison of the PTH and bicarbonate levels suggested the stability of osteolysis and of the transcellular membrane shift of phosphate. Also, administration of CaCO3 before a meal is associated with significantly lower plasma corrected calcium, suggesting less absorption of calcium, which may be an advantage but only in hypercalcemic patients. There is no reason other than the prevention of its hypercalcemic effect to recommend the administration of CaCO3 just before meals rather than during meals.
Oxygen‐Carrying Macromolecules: Therapeutic Agents for the Treatment of Hypoxia
Authors: Nosé Yukihiko
Published: March 2003

Abstract: A stabilized form of hemoglobin as oxygen‐carrying macromolecules was developed. It had an approximately 90,000 dalton molecular weight, and its intravascular half‐life was 36 h. Its molecular size was less than 0.1 μ m. Its hemoglobin concentration was 6% and its P50 value was 24 mm Hg. Oxygen carried inside plasma performs differently than oxygen carried inside red cells. Less than 0.3 cc of oxygen in 100 ml of blood is available in the plasma while 14–19 ml of oxygen is carried inside the red cells. Thus, less than 5 cc of oxygen is available inside the plasma of the entire body. When a patient develops hypovolemic shock, the red cells are bypassed and are not perfused directly inside the tissues. However, the plasma should reach hypoxic tissues. Thus, infusion of oxygen‐carrying macromolecules into the plasma should be therapeutically effective even when infusing less than 100 ml of stabilized hemoglobin solution under shock conditions. The basic physiology of oxygen‐carrying macromolecules is described in detail, which is different from the physiology of oxygen‐carrying red cells.