bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the anti‐complement agents, FUT‐175 and K76COOH, in discordant xenotransplantation
Authors: Kobayashi T. , Neethling F.A. , Taniguchi S. , Ye Y. , Niekrasz M. , Koren E. , Hancock W.W. , Takagi H. , Cooper D.K.C.
Published: November 2008

Abstract: We examined whether hyperacute rejection (HAR) of a discordant xenograft in a nonhuman primate model could be inhibited by the anticomplement agents, FUT‐175 (FUT) and K76COOH (K76). The inhibitory effect of FUT and K76 on baboon sera was studied in vitro by i) complement‐mediated hemolysis of sheep erythrocytes (by measuring serum CH50) and ii) cytotoxicity to cultured pig kidney (PK15) cells. The in vivo administration of FUT (at 0.2–25 mg/kg/h i.v. continuously) and K76 (50 mg/kg i.v. bolus) allowed evaluation of the serum levels of these drugs. Both FUT and K76 inhibited serum CH50 in a concentration‐dependent manner. An enhanced effect was obtained by combining K76 with FUT therapy. High concentrations of FUT (>10‐4 M) and K76 (>103 μxg/ml) were necessary to suppress serum CH50 to <5% of the normal level. However, PK15 cytotoxicity remained at >50% in the presence of i) 10‐4 M of FUT, ii) 103 μg/ml of K76, and iii) 10‐6 M of FUT + 103 μg/ml of K76. Pig heart transplantation (HTX) was performed in two baboons receiving FUT (1 mg/kg/h i.v. continuously) and K76 (at 200 mg/kg ×1 or 400 mg/kg + 200 mg/kg × 2 i.v, respectively). Cytotoxicity of the serum to PK15 cells at the time of HTX showed 39% and 1% cell death, respectively, in these two baboons, and the CH50 level was 1% (of control level) and 0%, respectively. Graft survival was 4.5 hours and 10 hours (with death of the baboon), respectively (compared with a mean of 29 minutes in control experiments). Both excised grafts showed typical features of hyperacute rejection. Immunopathological studies revealed deposition of C1q, C3d, C6, properdin, and Factor B, demonstrating that complement activation was not fully inhibited by FUT and K76. We conclude that i) FUT and K76 are indeed potent complement inhibitors, ii) the dosages of FUT and K76 necessary to suppress complement‐mediated injury cannot be extrapolated from previously reported data obtained from serum CH50 levels, and iii) higher (possibly toxic) dosages will be required to inhibit complement activation completely. It seems unlikely that HAR will be prevented by these drugs alone, although they may be beneficial when combined with other forms of therapy.
Host marrow has a competitive advantage that limits donor hematopoietic repopulation in mixed xenogeneic chimeras
Authors: Gritsch H. Albin , Sykes Megan
Published: November 2008

Abstract: In mixed xenogeneic (rat/mouse) chimeras, in which both donor and host hematopoietic cells coexist, donor hematopoiesis eventually declines, despite apparent immunological tolerance of the host to the donor. To explain this observation, we hypothesized that donor hematopoietic cells might have a competitive disadvantage in a xenogeneic environment. Since SCID (severe combined immunodeficient) bone marrow cells (BMC) are unable to produce functional B and T lymphocytes, they might compete for myeloid but not lymphocytic reconstitution of the animals, whereas marrow from the normal congenic strain, C.B‐17, would compete for repopulation of both lineages. We therefore evaluated the capacity of SCID and C.B‐17 mouse marrow to inhibit repopulation by rat BMC in irradiated SCID mouse recipients. Nine weeks after administration of T‐cell depleted (TCD) F344 rat BMC alone to 3 Gy‐irradiated SCID mice, rat cells of both the myeloid and the lymphoid lineages were readily detectable among peripheral blood leukocytes. Rat plus SCID mouse BMC reconstitution resulted in a marked reduction in rat myeloid repopulation, without affecting rat lymphoid repopulation. Rat plus TCD normal C.B‐17 mouse BMC, on the other hand, completely inhibited repopulation of all rat lineages by 9 weeks. Since mouse marrow inhibited only the repopulation by rat cells of the lineages that the mouse marrow was itself capable of generating, we conclude that physiologic factors, such as species specificity or selectivity of cytokines, adhesion molecules, and other molecules important for hematopoiesis, provide a competitive advantage to host marrow over xenogeneic hematopoietic cells. This physiologic barrier must be overcome in addition to immunologic barriers if bone marrow transplantation (BMT) is to provide a feasible approach to inducing xenograft tolerance. In addition, we describe the development of a chronic graft‐vs.‐host‐disease (GVHD)‐like syndrome in SCID mouse recipients of TCD rat marrow.
Demonstration of the functional importance of the Gal epitope in an ex vivo model of xenotransplantation
Authors: Iange M.J. , Tearle R.G. , Aminian L. , Romanella M. , Adam W.R. , Pearse M.J. , D'Apice A.J.F.
Published: November 2008

Abstract: The galactose a 1‐3 galactose terminal disaccharide (Gal epitope) has been identified as the major porcine xenoantigen recognised by xenoantibody in human plasma. Elimination or suppression of the epitope or antibody will be a major factor in overcoming hyperacute rejection. Inhibition of the antibody by depletion or elimination of the epitope by gene knockout may reveal the importance of other xenoantibodies, and in addition elimination of the epitope may unmask or produce other xenoantibody combinations. This study aims to determine the relative importance of anti‐Gal antibody and Gal epitope elimination in a functional model of xenotransplantation, ex vivo perfusion of mouse hearts with human plasma on a Langendorff apparatus. Perfusion of mouse hearts with human plasma depleted of anti‐Gal antibody demonstrates a protective effect compared to hearts perfused with undepleted plasma with prolongation of survival time from 24.1 to 44.5 min. Similarly, elimination of the epitope is also protective. Hearts from Gal knockout mice, which were generated by gene targeting of the al,3 galactosyltransferase gene, and hearts from appropriate control mice were perfused with human plasma. Gal knockout mice hearts demonstrated an increase in survival time from 10.2 to 33.8 min compared to control hearts. This was accompanied by a decrease in C3c and IgM, but little change in IgG deposition. The protective effect is incomplete, probably due to the effect of antibodies against non‐Gal xenoantigens. There was no functional evidence for generation of neo‐antigens in the Gal KO mice that were I recognised by naturally occurring human xenoantibodies.
Xenogeneic mouse anti‐human NK cytotoxicity is mediated via perforin
Authors: Smyth Mark J. , Thia Kevin Y.T. , Kershaw Michael H.
Published: November 2008

Abstract: Natural killer (NK) cells have been identified among the cell populations thought to participate in delayed xenograft rejection. We investigated the relative contribution of perforin‐ and Fas ligand‐pathways in mouse NK‐mediated xenocytotoxicity generated in response to cytokine or xenoantigenic stimulation. Freshly isolated spleen cells exhibited little NK cell‐mediated cytotoxicity against human PHA‐stimulated peripheral blood mononuclear cells (PBMC) or the human NK‐sensitive cell line, K562, despite efficiently lysing mouse NK‐sensitive Yac‐1 target cells. However, after incubation of mouse spleen cells for 7 to 10 days in the presence of mitomycin C‐treated xenogeneic human PBMC or exogenous interleukin‐2 (IL‐2), the NK activity of cultured mouse adherent lymphocytes (A‐NK) against human targets increased dramatically. A‐NK cells generated in immunocompetent mice displayed significant lysis of human targets, as did effector cells generated in gld mice with a mutated Fas ligand. By contrast, the low cytotoxic activity of A‐NK from perforin‐deficient mice responding to K562 target cells suggested that NK xenocytotoxicity is perforin‐mediated. Perforin‐deficient mouse A‐NK cells only lysed Fas‐sensitive human PBMC and K562‐Fas targets to a minor extent. Overall, these data suggest that A‐NK cell xenolysis is predominantly mediated by perforin, irrespective of the stimulus (cytokine or cellular) provided.
Legal implications of xenotransplantation
Authors: Chae Sanders J. , Cooper Datid K.C.
Published: November 2008

Abstract: Xenotransplantation (XTx) offers a possible solution to the severe shortage of organs for transplantation, but it will raise new legal questions. There are currently no legal impediments to XTx in the United States nor do animals possess common law or constitutional rights that would prevent it. The law remains indefinite regarding what constitutes a human being, allowing the possibility that legal arguments will be raised regarding the legal status of transgenic animals expressing human tissues or cells. As successful XTx will eliminate the organ shortage, Congress or state legislatures will have to reconsider the need for the current centralized system of allocation and distribution of organs, for this could be replaced by a commercial system based on market forces. The most significant legal issue relating to XTx is probably the potential threat to the public health and safety through the transmission of an infectious disease. The Public Health Service has recently issued draft guidelines which make recommendations about how XTx procedures might be performed. These guidelines currently have no legal authority but offer insight into how XTx might be regulated if it becomes a clinical, reality. Existing federal laws, however, empower federal agencies to regulate XTx, in part because of the potential risk to the public health. Additionally, tort liability will impose legal pressure on transplant centers to minimize the level of risk that the general public might face. The most difficult questions facing legislatures and the Public Health Service may well prove to be those raised by the behavior of individual patients or their social contacts who do not comply with the guidelines/regulations relating to long‐term monitoring for infectious complications.
Synergistic actions of the vitamin D analogue MC 1288 and 15‐deoxyspergualin in xenotransplantation
Authors: Johnsson Cecilia , Tufveson Gunnar , Binderup Lise , Karlsson‐Parra Alex
Published: November 2008

Abstract: The vitamin D analogue MC 1288 (20‐epi‐1α,25‐dihydroxycholecalciferol) effectively postpones rejection of cardiac, intestinal, skin, and aortic allografts. MC 1288 binds to the vitamin D receptor and is thus assumed to exert its immunosuppressive effects via the same mechanisms as 1α,25‐dihydroxycholecalciferol, the active form of vitamin D. 1α,25‐Dihydroxycholecalciferol has been demonstrated to inhibit the production of various cytokines (interleukin‐2, interferon‐γ, granulocyte macrophage colony‐stimulating factor, and interleukin‐12) and to prevent B lymphocyte secretion of immunoglobulins. In the present study MC 1288 was evaluated for its ability to prevent rejection of mouse‐to‐rat cardiac xenografts, alone and in combination with 15‐deoxyspergualin (DSG). Combined treatment with MC 1288 (given days ‐1 to 9) and DSG (given day ‐1 and onward) postponed rejection from day 3.0 (untreated recipients) until day 19.5. In rats treated with MC 1288 or DSG as monotherapy, rejection occurred after 3.0 and 7.5 days, respectively. Functioning grafts, obtained on day 9 from recipients treated with MC 1288 and DSG in combination, displayed an almost normal morphology without any obvious deposition of immunoglobulins in the vessels of the grafts and with just a few infiltrating cells. Thus, we have demonstrated synergistic actions of MC 1288 and DSG in delaying rejection of xenografts. Analysis of cellular infiltration, immunoglobulin deposition and graft survival times in the various treatment groups indicate a combined inhibitory effect of these two drugs on the level of macrophage effector function, direct or indirect via T lymphocytes, as well as on antibody production.
Correction of congenital hyperbilirubinemia in homozygous Gunn rats by xenotransplantation of hamster livers
Authors: Wakizaka Yoshilaka , Miki Toshio , Rao AbdulS. , Wang Xue , Goller April L. , Demetris Anthony J. , Fung John J. , Starzl Thomas E. , Valdivia Luis A.
Published: November 2008

Abstract: The homozygous Gunnj/j rat is an animal model for Crigler‐Najjar syndrome in which the lack of the enzyme uridine diphosphoglucoronate‐glucuronosyltransferase (UDP‐GT) results in congenital unconjugated nonhemolytic hyperbilirubinemia. Because the binding of bilirubin to albumin in plasma varies from species to species, xenotransplantation (XTx) of liver afforded in this model the opportunity to study the interactions between xenoproteins of the donor and bilirubin of the recipient. For this purpose, orthotopic liver transplantation (OLTx) was performed from hamster to adult Gunnj/j rats. No immunosuppression (IS) was given to controls (Group I, n=5) and to OLTx recipients of syngeneic (Gunnj/j rat) grafts (Group II, n=5), whereas tacrolimus (1 mg/kg/day × 15 days, IM) and cyclophosphamide (8 mg/kg/day × 7 days, IP) were administered to animals receiving hamster xenografts (Group III, n=11). While untreated animals (Group I) died within 7 days (6.8±0.2 days) post‐transplantation (Tx), the use however of IS resulted in prolonged (30.2±6.8 days) survival of xenogeneic recipients (Group III) who eventually succumbed to rejection. A precipitous decline in total serum bilirubin (TBili) from pre‐operative levels of 5.3±1.0 mg/dL to 0.5±0.2 mg/dL was noted in both Group I and III animals, an observation that sustained itself only in the latter group during the course of their follow‐up. The decrease in TBili was also associated with a contemporaneous increase in biliary concentration of conjugated bilirubin. No noticeable reversal of hyperbilirubinemia was however observed in OLTx recipients of syngeneic grafts (Group II). Taken together, these data suggest that hamster albumin and hepatocyte‐associated xenoproteins and enzymes involved in the process of membrane transport and glucuronidation of bilirubin, functioned efficaciously after OLTx in Gunnj/j rats, resulting in the I reversal of the inborn error of metabolism for the duration of follow‐up.
Prediction of failed labor induction in parous women at term: Role of previous obstetric history, digital examination and sonographic measurement of cervical length
Authors: Park Kyo Hoon , Hong Joon‐Seok , Shin Dong Myung , Kang Woong Sun
Published: November 2008

Aim:  To examine the predictive value of previous obstetric history, Bishop score, and sonographic measurement of cervical length for predicting failed induction of labor in parous women at term.

Methods:  This prospective observational study enrolled 110 consecutive parous women at term with singleton gestations scheduled for the induction of labor. Transvaginal ultrasound for measurement of cervical length was performed and the Bishop score was assessed using digital examination. Univariate and multivariate analyses were used for statistical analysis.

Results:  Labor induction failed in 15 women (14%). In terms of previous obstetric history, women with only previous mid‐trimester loss or preterm delivery had a significantly higher risk of failed labor induction than those with at least one previous term delivery. Logistic regression demonstrated that previous obstetric history and the Bishop score, but not cervical length, were found to be significant and independent contributing factors for failed labor induction. In the receiver operating characteristic curves, the best cut‐off value of the Bishop score for the prediction of failed labor induction was 3, with a sensitivity of 73% and a specificity of 44%.

Conclusions:  The previous obstetric history (i.e. only previous mid‐trimester loss or preterm delivery) and the Bishop score independently predicted the failure of labor induction in parous women; however sonographic measurement of the cervical length appeared to have a poor predictive value for the risk of failed induction.
Sheep and rabbit genital tracts and abdominal wall as an implantation model for the study of surgical mesh
Authors: Krause Hannah , Goh Judith
Published: November 2008

Aim:  In order to evaluate the biocompatible and biomechanical properties of surgical mesh, suitable animal models are required. This paper assesses the sheep and rabbit genital tracts as potential models for direct vaginal implantation of mesh for use in pelvic floor surgery.

Methods:  Sheep and rabbits were implanted with surgical mesh in the abdominal wall and genital tract. After 12 weeks, the implantation sites were assessed and the mesh was explanted for histological review.

Results:  Technical aspects of vaginal surgery on the sheep and rabbits are described. Implantation of mesh was achievable in both the sheep and rabbit genital tracts. Following 12 weeks of mesh implantation, there was a high rate of mesh erosion through both the sheep and rabbit vaginal epithelium.

Conclusions:  Vaginal mesh erosion was present in both the sheep and rabbit genital tract model. The properties of sheep and rabbit vaginal epithelium require further evaluation to determine their comparability to human vaginal epithelium.
16S rRNA gene‐based phylogenetic microarray for simultaneous identification of members of the genus Burkholderia
Authors: Schönmann Susan , Loy Alexander , Wimmersberger Céline , Sobek Jens , Aquino Catharine , Vandamme Peter , Frey Beat , Rehrauer Hubert , Eberl Leo
Published: November 2008

For cultivation‐independent and highly parallel analysis of members of the genus Burkholderia, an oligonucleotide microarray (phylochip) consisting of 131 hierarchically nested 16S rRNA gene‐targeted oligonucleotide probes was developed. A novel primer pair was designed for selective amplification of a 1.3 kb 16S rRNA gene fragment of Burkholderia species prior to microarray analysis. The diagnostic performance of the microarray for identification and differentiation of Burkholderia species was tested with 44 reference strains of the genera Burkholderia, Pandoraea, Ralstonia and Limnobacter. Hybridization patterns based on presence/absence of probe signals were interpreted semi‐automatically using the novel likelihood‐based strategy of the web‐tool PhyloDetect. Eighty‐eight per cent of the reference strains were correctly identified at the species level. The evaluated microarray was applied to investigate shifts in the Burkholderia community structure in acidic forest soil upon addition of cadmium, a condition that selected for Burkholderia species. The microarray results were in agreement with those obtained from phylogenetic analysis of Burkholderia 16S rRNA gene sequences recovered from the same cadmium‐contaminated soil, demonstrating the value of the Burkholderia phylochip for determinative and environmental studies.
Understanding the metabolome – challenges for metabolomics
Authors: Walsh M. C. , Nugent A. , Brennan L. , Gibney M. J.
Published: November 2008

Metabolomics is a comprehensive method for metabolite assessment, measuring the overall metabolic signature of biological samples. This approach opens up many possibilities in areas such as new biomarker discovery and hypothesis generation. The application of metabolomics is growing rapidly but many challenges must first be addressed before it can reach its true potential. Metabolomics organisations are currently working towards guidelines for commonality in metabolomics experiments as development of optimal methodologies and study designs are needed. Blood and urine appear to be the most useful biofluids for nutrition research, but an array of biofluids, cells and tissues can be used. The key steps required for the successful understanding of metabolomics data are compound identification and biological interpretation. Many databases of compounds are available but are still under construction with much information remaining to be populated. An understanding of the effects of normal physiological variation on metabolic profiles is essential for accurate interpretation of profile changes, particularly in human studies, because of diversity in lifestyle and environmental factors. The effects of factors such as ethnicity, gender, age, body composition, health, dietary intake, physical activity, gut microflora and stress need to be further explored in order to advance the understanding of the human metabolome and therefore improve data interpretation.
Influenza virus‐like particles produced by transient expression in Nicotiana benthamiana induce a protective immune response against a lethal viral challenge in mice
Authors: D’Aoust Marc‐André , Lavoie Pierre‐Olivier , Couture Manon M.‐J. , Trépanier Sonia , Guay Jean‐Martin , Dargis Michèle , Mongrand Sébastien , Landry Nathalie , Ward Brian J. , Vézina Louis‐P.
Published: November 2008

A strain‐specific vaccine represents the best possible response to the threat of an influenza pandemic. Rapid delivery of such a vaccine to the world's population before the peak of the first infection wave seems to be an unattainable goal with the current influenza vaccine manufacturing capacity. Plant‐based transient expression is one of the few production systems that can meet the anticipated surge requirement. To assess the capability of plant agroinfiltration to produce an influenza vaccine, we expressed haemagglutinin (HA) from strains A/Indonesia/5/05 (H5N1) and A/New Caledonia/20/99 (H1N1) by agroinfiltration of Nicotiana benthamiana plants. Size distribution analysis of protein content in infiltrated leaves revealed that HA was predominantly assembled into high‐molecular‐weight structures. H5‐containing structures were purified and examination by transmission electron microscopy confirmed virus‐like particle (VLP) assembly. High‐performance thin layer chromatography analysis of VLP lipid composition highlighted polar and neutral lipid contents comparable with those of purified plasma membranes from tobacco plants. Electron microscopy of VLP‐producing cells in N. benthamiana leaves confirmed that VLPs accumulated in apoplastic indentations of the plasma membrane. Finally, immunization of mice with two doses of as little as 0.1 µg of purified influenza H5‐VLPs triggered a strong immune response against the homologous virus, whereas two doses of 0.5 µg of H5‐VLPs conferred complete protection against a lethal challenge with the heterologous A/Vietnam/1194/04 (H5N1) strain. These results show, for the first time, that plants are capable of producing enveloped influenza VLPs budding from the plasma membrane; such VLPs represent very promising candidates for vaccination against influenza pandemic strains.
An all‐Ireland epidemiological study of MND, 2004–2005
Authors: Donaghy C. , O’Toole O. , Sheehan C. , Kee F. , Hardiman O. , Patterson V.
Published: November 2008

Background and methods:  We conducted an all‐Ireland population‐based prospective epidemiological survey of motor neurone disease (MND) using the Northern Ireland and Republic of Ireland MND registers to examine the incidence and prevalence of the disease over the period 2004–2005.

Results and conclusions:  Incidence of MND was 1.9 per 100 000 person‐years and rates were comparable in both the north and south of Ireland. Prevalence of MND was 5.0 per 100 000 population. When compared with previous published surveys of MND performed in the Republic of Ireland over the last 10 years, rates of disease have remained relatively constant. When standardized to the 1990 US population, the incidence of MND in Ireland was found to be consistent with other European prospective surveys of MND.
A Methodological Overview of Network Vulnerability Analysis
Authors: MURRAY ALAN T. , MATISZIW TIMOTHY C. , GRUBESIC TONY H.
Published: November 2008

Evaluating network infrastructures for potential vulnerabilities is an important component of strategic planning, particularly in the context of managing and mitigating service disruptions. Many methods have been proposed to facilitate such analysis, providing different interpretations of infrastructure vulnerability. The primary approaches that have been employed for network vulnerability analysis can be broadly classified as scenario‐specific, strategy‐specific, simulation, and mathematical modeling methodologies. Research on network vulnerability assessment has traditionally focused on one of these methodologies without consideration of the others. This article highlights the important implications of methodology for both infrastructure planning and policy development. To better understand the theoretical and practical trade‐offs associated with methodology selection, this article provides a review of these categories of analysis, examining benefits and shortcomings with regard to practical planning issues and policy interpretation.
Spatial and temporal projected distribution of four crop plants in Egypt
Authors: Hegazy Ahmad K. , Medany Mahmoud A. , Kabiel Hanan F. , Maez Mona M.
Published: November 2008

This study focuses on the management of the local agroecosystems in order to adapt planting or sowing practices for the projected climate change scenarios. It is projected that there will be increased air temperature throughout all four seasons in the coming 100 years, from the southern towards the northern parts of Egypt. The objective of this study is to investigate the influence of that increased air temperature on the spatial and temporal distribution of four of the major economic crops in Egypt. The study species are cotton (Gossypium barbadense L., cv. Giza 89), wheat (Triticum aestivum L., cv. Gemiza 9), rice (Oryza stiva L., cv. Sakha 101) and maize (Zea mays L., cv. Hybrid 10). Optimum air temperature allowing maximum growth for each of the study crop cultivars and the current and projected air temperature patterns in the future years were used for projection of the seasonal and crop distribution maps in the years 2005, 2025, 2050, 2075 and 2100.

Results showed that sowing dates of a target crop may be managed in order to allow maximum predicted planting area in the same region. The current maximum area suitable for planting the Cotton crop in Egypt (104 thousand Fadden/year; one Fadden = 0.96 hectare or 0.42 acre) showed few variations over the coming hundred years. In this case, the sowing dates should be changed from the hotter months (February to April) to the cooler months (January to February). Alternatively, a great reduction in the area planted by Wheat crop was predicted in the coming 100 years. Despite the early planting, a reduction of about 147 thousand Fadden/year was projected by the year 2075. On the other hand, with earlier sowing dates, the maximum areas that are planted by Rice and Maize may not be greatly affected by the projected increase in air temperature.
Quantitative Indices of Intra‐Aortic Balloon Pump (IABP) Dependence During Post‐Infarction Cardiogenic Shock
Authors: Sturm James T. , Fuhrman Thomas M. , Igo Stephen R. , Holub Daniel A. , McGee Michael G. , Fuqua John M. , Norman John C.
Published: November 2008

In an attempt to quantitate intra‐aortic balloon pump (IABP) dependence and differentiate retrievable post‐infarction cardiogenic shock situations, thirty‐five patients were analyzed in regard to age, duration of IABP support, and hemodynamic performance. Survivors were younger than non‐survivors (P<0.01) and the duration of IABP support in survivors was greater than that of non‐survivors (P<0.05). When duration of IABP support was plotted against age, three zones of increasing dependence and mortality were apparent. In Zone 1 (ages 32–40), there was no dependence or mortality; in Zone 2 (ages 40–65, IABP durations < 250 hours), there were several instances of dependence and a 63% mortality; in Zone 3 (ages gt; 65 or IABP durations > 250 hours), there was a 100% mortality. IABP dependence was best recognized by time‐course trajectory plots of cardiac index versus systemic vascular resistance. Three trends were observed. All patients who improved to Class A (CIgt; 2.1 L/min/m2, SVR< 2100 dynes sec cm‐5) survived unless they succumbed to sudden ventricular dysrhythmias. Patients who remained in Class B (1.2 L/min/m2 < CI< 2.1 L/min/m2, with SVR's < 2100 dynes sec cm‐5) for 7–14 days were IABP‐dependent and eventually expired. Patients who deteriorated to or remained in Class C (CI< 1.2 L/min/m2 or SVR> 2100 dynes sec cm‐5) expired early despite IABP support and were considered irretrievable.

This study suggests that post‐infarction cardiogenic shock IABP‐dependence can be quantitated to a certain degree. Post‐infarction IABP‐dependent patients are relatively young (40–55), do not expire during the first 50 hours of IABP support, neither improve nor deteriorate during the second 50 hours of support, and remain in Class B for 7–10 days without the occurrence of life‐threatening ventricular dysrhythmias. In such situations, sufficient time may be available for cardiac catheterization to determine the appropriateness of subsequent operative interventions.
Effects of Ticlopidine on Thrombotic Obstruction of A‐V Shunts and on Dialysance of Artificial Kidneys
Authors: Maeda Kenji , Usuda Masatsune , Kawaguchi Shunsuke , Shinzato Tohru , Saito Akira , Ohta Kazuhiro , Kobayashi Kaizo , Ohbayashi Shogo , Narita Masayasu
Published: November 2008

Administration of ticlopidine, a new inhibitor of platelet aggregation, during hemodialysis to two patients with thrombotic occlusion of external A‐V shunts markedly suppressed the obstruction of the shunt and improved anemia. Consequently, it was concluded that this drug may be useful for maintaining good blood flow and good patency of shunts in patients undergoing dialysis.

In order to determine the dialyzer efficiency during dialysis, the reduction rate of the dialyzer was determined in vitro. The dialyzer reduction rates for urea, creatinine, uric acid, and phosphoric acid were all lowered after dialysis, and the administration of ticlopidine resulted in a suppression of the drop in the reduction rate.

Based on the inhibitory effect of ticlopidine on platelet aggregation, it was assumed that a close correlation may exist between adhesion and aggregation of platelets and the drop in the efficiency of the dialyzer during dialysis as well as thrombotic obstruction of shunts.
Are the Jarvik Artificial Ventricles Limited By Inflow Resistance?
Authors: Lioi Anthony P. , Nielsen Steven D. , Olsen Don B.
Published: November 2008

The pneumatic total artificial heart has been assumed to be inflow limited. Mock circulation studies on the Jarvik‐5 and Jarvik‐7 artificial ventricles seemed to support this assumption because a Starling's response comparable to the natural heart was not achieved. Unfortunately, mock circulation studies do not separate the effects of valvular regurgitation from inflow resistance. By using a simple filling tank, filling times were determined for the Jarvik ventricles that were a function of inflow resistance alone. Theoretical maximum cardiac outputs based on these inflow resistance‐dependent filling times were then calculated. For filling pressures around 5 mmHg and under modest diastolic vacuum of 5 cm H2O, the Jarvik ventricles yield a theoretical cardiac output as good as the natural heart's. Thus, inflow resistance is not a limiting factor and valvular regurgitation is left as the most likely cause of a less than optimal Starling's response on mock circulation and in vivo.
Numerical Simulation of Blood and Plasma Flow through the Petschek Flow Chambers
Authors: Johnson Webster R. , Madras Peter N.
Published: November 2008

The Stagnation Point Flow Experiment is a popular means for studying blood‐surface interactions in a surface strain rate gradient. The strain rate distribution on the test surface of the flow chamber used in this experiment was originally assumed to be simply proportional to the radial distance from the stagnation point. A numerical simulation of the flows through the five most frequently used chambers shows that this is true only for one of the chambers, approximately so for another, and not true for the other three. An additional numerical simulation indicates the blood should purge the saline priming liquid within a few seconds at the beginning of the experiment.
Performance of a New Type of Blood Oxygenator
Authors: Merchuk Jose C. , Dana Rene D. , de Lew Maria M. , Dvilansky Alexander , Meyerstein Naomi , Tamir Abraham
Published: November 2008

A new type of direct‐contact oxygenator has been tested satisfactorily on dogs in nine experiments. It is based on the principle of the “packed column“ and has the advantage of a small hold‐up (meaning a small priming volume), no formation of foam, and gentle flowing of the blood. The apparatus is simple enough to be commercially available at a low price and discarded after use. Both PO2 increase and PCO2 decrease were satisfactory and plasma hemoglobin values remained low after 75 minutes of perfusion. Preliminary in vitro experiments on ox and human blood showed a low degree of blood damage.
Acid Citrate Dextrose Reduces Platelet Retention During In Vitro and In Vivo Dog Hemoperfusion: A Comparative Study of Different Charcoal Adsorbers
Authors: Tangerman Albert , Snel Pleun , van Schaik Annie , van Tongeren Jan H.M.
Published: November 2008

Hemoperfusion through charcoal adsorbers has often been proposed for use in exogenous and endogenous intoxication. A serious drawback of this technique is the often encountered loss of platelets and leucocytes. In vitro hemoperfusion studies with heparinized human blood and in vivo hemoperfusion of heparinized Labrador dogs through different types of charcoal adsorbers (Becton‐Dickinson [B‐D], Gambro, Haemocol) clearly demonstrated that addition of the anticoagulant acid citrate dextrose (ACD) might reduce the loss of platelets. ACD seemed to have no distinct influence on leucocyte retention.
The Effect of Hemofiltration on Fiber Platelet Concentration
Authors: Drake Kenneth L. , Eckstein Eugene C.
Published: November 2008

Experimental methods and apparatus were developed to measure platelet concentration in an ultrafiltering hollow fiber with blood and ultrafiltrative flow rates that are characteristic of current hemofiltration practice. Values are presented for the adjusted local platelet concentration, which allows for the expected increase due to loss of ultrafiltrate volume. Platelet concentrations in fiber samples are of interest since ultrafiltration can create platelet polarization in a fashion similar to the concentration polarization that occurs for proteins. For many combinations of inlet flow rate, ultrafiltrative flow rate, and fiber dimension, there are significant elevations in adjusted fiber platelet concentration. The adjusted platelet concentrations of the outflow samples are nominally equal to those of the feed (reservoir) samples; thus, reaction and adhesion of platelets is not a significant source of fiber concentration. Experiments with fibers of different diameters indicate that, as expected in concentration polarization, the excess platelets are located near the wall. Data for the fiber platelet concentration depend in a complex fashion upon the inlet wall shear rate and ultrafiltrative velocity. For certain fixed ultrafiltrative velocities, a maximum fiber platelet concentration occurs at an intermediate inlet wall shear rate. The data are qualitatively explained by an extension of a published model involving diffusive, ultrafiltrative, and wall‐induced fluxes of red cells and platelets.
Development of Means to Augment Peritoneal Urea Clearances: The Synergistic Effects of Combining High Dialysate Temperature and High Dialysate Flow Rates with Dextrose and Nitroprusside
Authors: De Santo Natale G. , Capodicasa Giuseppe , Capasso Giovambat‐tista , Giordano Carmelo
Published: November 2008

By combining: a) nitroprusside (4.5 mg/L); b) dextrose concentration of 42.5 gm/L; c) dialysate temperature of 42°C and d) dialysate flow rates of 3.5 L/hour in seven uremic subjects on C APD, it was possible to increase peritoneal urea clearance up to 35.6 ± 3.8 ml/min/1.73 m2 (range 30.3 to 42.2). This effect in six out of seven cases was associated with a fall in blood pressure and an increase in heart rate. This study is the first which deals with a combination of these factors and demonstrates that this approach is easy to handle, does not require the use of mechanical devices, and is available at any bedside.
Maintenance Hemodialysis in End‐Stage Renal Disease Associated with Spinal Cord Injury
Authors: Vaziri N. D. , Bruno A. , Byrne C. , Mirahmadi M. K. , Nikakhtar B. , Gordon S. , Zeien L.
Published: November 2008

Data on maintenance hemodialysis in end‐stage renal disease (ESRD) associated with spinal cord injury (SCI) are lacking. Forty‐three SCI‐ESRD patients treated with hemodialysis in our unit were retrospectively studied. A control group of ESRD patients without SCI were included for comparison. Predialysis concentrations of Na, K, bicarbonate, creatinine, albumin, calcium, and phosphorus and anion gap were significantly lower in the SCI group than in the control group. In contrast, chloride concentration was significantly higher in the SCI patients. Hemodialysis was equally effective in providing azotemia control and acid‐base, electrolyte, and fluid balance in both groups. Interdialytic weight gain in the SCI group was significantly less than that of the control group. Hypotensive episodes during dialysis were quite common in the SCI patients. Interestingly, hypertensive episodes during or shortly after dialysis were also noted with considerable frequency. The hypotensive episodes usually responded to blood flow reduction and/or fluid administration. Hypertensive episodes were usually mild to moderate and reversed with continued dialysis without requiring vigorous intervention. The leg cramps often seen in ambulatory patients due to rapid ultrafiltration and fluid shifts were uncommon among the SCI patients. However, diffuse painful muscle spasms caused by uninhibited spinal reflexes were observed with considerable frequency and presented a difficult therapeutic problem. Due to prolonged immobilization and other factors, SCI‐ESRD patients appear to be at high risk of thromboembolic disorders. SCI‐ESRD patients thus appear to differ from the ambulatory ESRD patients from both clinical and biochemical viewpoints. These specific feaures can be of significant value with respect to the dietary and therapeutic considerations.
How to Comply with the Food and Drug Administration's “Investigational Device Exemption (IDE)“ Regulations Including an Application Form (Revised January 1982) Prepared by the ASAIO Standards Committee,
Authors: Morton William A. , Dobelle William H. , Lysaght Michael J. , Serkes Kenneth , Siemsen Arnold , Villarroel Fernando
Published: November 2008

This is a revision of the IDE Application Form, “How to Comply with the Food and Drug Administration's New ‘Investigational Device Exemption (IDE)’ Regulations, Including an Application Form“ originally published in Artificial Organs, Volume 4, Number 4, November 1980.

This publication updates the IDE application form to facilitate compliance with the amended investigational device exemption regulations now in effect.
Intermittent Vascular Access for Extracorporeal Circulation in Conscious Rats: A New Technique
Authors: Tabata Yoichiro , Chang Thomas Ming Swi
Published: November 2008

A new technique is described for repeated intermittent access to the systemic circulation in fully conscious rats for infusion or extracorporeal circulation. The femoral artery and vein of each rat were cannulated. The cannulas were then passed subcutaneously and exteriorized through the skin of the tail 2 cm from its base. The exposed cannulas were protected by a special plastic device. This new approach did not immobilize the rat except during access to the circulation; even then, only the distal portion of the tail was immobilized, thus allowing the animal to move freely. This way repeated access to the systemic circulation was easily achieved in the fully conscious rat.
Furosemide‐Induced Increase in Urinary and Peritoneal Excretion of Uric Acid During Peritoneal Dialysis in Patients with Chronic Uremia
Authors: Grzegorzewska Alicja , Baczyk Kazimierz
Published: November 2008

Intermittent peritoneal dialysis was performed in 17 patients with chronic uremia in order to observe the effect of furo‐semide added to the dialysate on urinary and peritoneal elimination of uric acid. Two kinds of dialysate were used: moderately hypertonic (osmolality, 431.2 mOsm/kg of water) and slightly hypertonic (osmolality, 368.9 Osm/kg of water). Significant increases in urine volume, urinary and peritoneal excretion of uric acid, and renal and peritoneal clearances were found. The increase in urinary excretion of uric acid exceeded that of urine volume. These findings were interpreted to be the result of furosemide action on renal function after being transferred through the peritoneum into the blood stream with the concomitant increase in the uric acid shift from the circulation into the peritoneal cavity. We concluded that the addition of furosemide is useful in increasing uric acid elimination in patients with chronic uremia.
Electrical Energy Converters for Practical Human Total Artificial Hearts‐An Opinion in Support of Electropneumatic Systems
Authors: Jarvik Robert K.
Published: November 2008

Summary: Until recently, most artificial hearts have served as research tools to acquire further knowledge necessary ultimately to design practical systems for human use. Transcutaneous systems or percutaneous systems utilizing permanently implanted energy converters, batteries, and electronics packages have a number of substantial problems that would not exist if most system elements were kept outside the body. These problems include physiologic control, fit and fixation, foreign body infection, hermetic sealing, cable insulation and fatigue, inherent system complexity, stringent requirements for maintenance‐free operation with long‐term high reliability, and high cost. Percutaneous systems, particularly those in which only the blood pump is implanted, are an attractive choice for practical systems in the near future. A wearable, battery‐powered electropneumatic total heart system should be developed.

A practical artificial heart is one that patients can live with. Tether‐free, electrically powered devices certainly have the potential to provide an acceptable quality of life. Energy converter design must be part of an integrated systems approach that someday makes the crucial decision to utilize either the transcutaneous or percutaneous approach. There are many difficult technical problems with transcutaneous systems that can be avoided with percutaneous leads. Furthermore, the percutaneous approach leaves external components accessible for maintenance and replacement without surgery. In my opinion, percutaneous portable electropneumatic systems have the best potential for practical application to large numbers of human patients within the foreseeable future. They are particularly suited to orthotopic total artificial hearts using free diaphragm or tethered‐sac designs. Their development should be emphasized at this time.
Increment in Dialysate Sodium with Sodium Chloride or Bicarbonate Addition
Authors: Raja Rasib M. , Fernandes Michael , Kramer Mark S. , Rosenbaum Jerry L. , Barber Kevin
Published: November 2008

Abstract: Hemodialysis was performed in 12 patients for 2 weeks each utilizing acetate dialysate containing 134 mEq/L sodium and dialysate containing 143 mEq/L sodium, achieved by the addition of sodium chloride or sodium bicarbonate to the acetate dialysate. Intradialytic morbidity was lower, dialysis hypoxemia less marked, and predialysis blood pH higher with the bicarbonate‐than with the chloride‐added dialysate. The long‐term use of sodium bicarbonate‐added dialysate in three patients was safe. Dialysate pH adjustment was not required. These findings suggest that the addition of sodium bicarbonate (50–75 g) to acetate dialysate may be preferred to sodium chloride for increasing dialysate sodium in selected patients.
Influence of Hemodialysis on Plasma Chemotactic Activity and the Chemotactic Responsiveness of Polymorphonuclear Neutrophils
Authors: Wierusz‐Wysocka Bogna , Wysocki Henryk , Czarnecki Ryszard , Siekierka Hanna , Baczyk Kazimierz , Wysocki Kazimierz
Published: November 2008

Abstract: Thirty patients with chronic renal failure on maintenance hemodialysis (HD) were studied. Plasma chemotactic activity was estimated using the “under agarose“ chemotaxis assay during the first 2 h of HD. It was found that in the fifth minute of HD, patients' plasma became chemotactic, reaching the maximum activity at the tenth minute. The chemotactic activity appearance correlated significantly with the decline in the number of the peripheral neutrophils. Patients' neutrophils, after a single passage through the cellophane coil of the dialyzer, revealed significant impairment of directed migration toward both complementary and bacterial chemoattractants. Moreover, the chemotactic properties of neutrophils obtained from dialyzed patients before HD were significantly lower than had been estimated in 15 nondialyzed patients with chronic renal failure. The results confirm HD‐induced complement activation and might explain the mechanisms of the increased susceptibility of dialyzed patients to bacterial infections.
Regeneration of Hemofiltrate by Anodic Oxidation of Urea
Authors: Köster K. , Wendt H. , Gallus J. , Krisam G. , Lehmann H. D.
Published: November 2008

Abstract: Urea can be oxidized electrochemically in a chloride solution to carbon dioxide, water, and nitrogen. The microkinetics of this hypochlorite‐mediated urea oxidation are elucidated. Based on this kinetic information, the optimal conditions and construction principles for an electrochemical reactor are deduced. The construction of a cheap, disposable oxidation cell and necessary auxiliary equipment are described. In vitro data are Reported for urea removal. A 36‐L volume was used to simulate a 60‐kg patient; 18 L was recirculated through a 0.12‐m2 oxidation cell. Within 3 h, 35 g urea could be removed from the system. The technical and economic possibilities as well as safety requirements for hemofiltrate regeneration to a reinfusable substitution solution by anodic urea oxidation are discussed critically. Although the process does not appear to be economically practical for discontinuous hemofiltration, it might be desirable for continuous (24 h/day) treatment.
Microencapsulation of Crystalline Insulin or Islets of Langerhans: An Insulin Diffusion Study
Authors: Leung Yin F. , O'Shea Geraldine M. , Goosen Mattheus F. A. , Sun Anthony M.
Published: November 2008

Abstract: Microcapsules containing insulin crystals or islets of Langerhans were made by extruding a mixture of insulin crystals or islets and sodium alginate into a calcium chloride solution, and then coating it with poly‐l‐lysine. When these microcapsules were incubated at 37d̀C, insulin could be detected readily in the medium, indicating that the microcapsular membrane is permeable to insulin. The efficiency of insulin encapsulation with crystalline insulin declined as the concentration in the sodium alginate mixture increased. Over 90% of the entrapped insulin was released after 3 days of incubation at 37d̀C, indicating that the rate of insulin release from the microcapsules requires modification if the microcapsules are to be used as a long‐term insulin delivery system. The amount of insulin secreted by the encapsulated islets was not significantly different from that of unencapsulated islets, suggesting the islets were not affected by the modified encapsulation process.