bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on the removal of anti‐pig xenoantibodies in the human by plasmapheresis/immunoadsorption
Authors: Rydberg Lennart , Hallberg Eva , Björckv Staffan , Magnusson Stefan , Strokan Valeri , Samuelsson Bo E. , Breimer Michael E.
Published: November 2008

Abstract: Removal of human preformed natural anti‐pig antibodies from the blood is a prerequisite before xenografting between pig and man can be performed. This work explores the effect of plasmapheresis and immunoadsorption (protein‐A sepharose) on the reduction and recurrence of anti‐pig antibodies in 14 patients. The anti‐pig antibody changes were evaluated by lymphocy to toxic, hemagglutinating, and endothelial cell ELISA techniques. The changes induced showed a similar pattern with all three techniques used. In addition, plasma from plasmapheresis treatments were perfused through pig kidneys and the reduction of anti‐pig antibodies was estimated by the mentioned in vitro techniques. The anti‐pig antibody titers could be reduced to low levels, but not completely eliminated, by 3–4 plasmapheresis sessions. The titers gradually returned to pretreatment levels or higher in a period of 1–2 weeks. A few patients showed signs of a more rapid resynthesis reaching pretransplant levels in 3–4 days. Protein A immunoadsorption satisfactory removed IgG but not IgM antibodies. In vitro perfusion of pig kidneys at 37°C showed a rapid reduction of anti‐pig antibody titers of 3–4 titer steps. The combination of 3–4 plasma exchanges followed by in vitro pig kidney perfusion completely removed all anti‐pig antibodies. Reduction of the anti‐pig lymphocyte and erythrocyte antibody titers by soluble oligosaccharides carrying terminal Galoc‐epitopes was only partly successful. A 40–60% inhibition was achieved by 5–10 mg saccharide/ml serum and no clear inhibition difference between di‐ and trisaccharides was found. Inhibition of plasma obtained after 3–4 plasmapheresis treatments with soluble Galα1‐di‐ and trisaccharides resulted in very low anti‐pig titers. Therefore one feasible pretreatment procedure, before pig to human xenotransplantation could be plasmapheresis for major reduction of anti‐pig antibody titer followed by neutralisation of the remaining antibodies by addition of soluble oligosaccharides or immunoadsorption with Galα‐1‐columns.
Donor‐specific growth factors promote swine hematopoiesis in severe combined immune deficient mice
Authors: Yang Yong‐Guang , Sergio Justin J. , Swenson Kirsten , Glaser Roseann M. , Monroy Rod , Sykes Megan
Published: November 2008

Abstract: Induction of a state of mixed hematopoietic chimerism following bone marrow transplantation is associated with donor‐specific tolerance in the concordant xenogeneic rat‐to‐mouse species combination. We are now attempting to induce such tolerance in a discordant species combination, pig to mouse. Our initial studies showed that non‐immune physiologic factors limited the level of swine hematopoietic reconstitution in severe combined immune deficient (SCID) mice. We have now examined the ability of swine‐specific growth factors, interleukin‐3 (IL‐3), granulocyte macrophage‐colony stimulating factor (GM‐CSF), and stem cell factor (SCF) to enhance repopulation by swine bone marrow cells in SCID recipients. The results indicate that swine IL‐3 promotes pig hematopoiesis in SCID mouse recipients. The percentage of swine class I+ cells in bone marrow, spleen, and peripheral blood was markedly increased by a 3‐week treatment course with porcine IL‐3. In longer‐term studies, the effect of IL‐3 was further enhanced by combining it with porcine GM‐CSF. Almost all repopulating porcine cells expressed a swine myeloid marker. Colony‐forming assays showed a correlation of the number of pig‐specific colonies with the number of swine cells detected by flow cytometry in transplanted‐SCID bone marrow recipients. Porcine CD2+ cells which did not express CD4 or CDS coreceptors were also detected in SCID mouse recipients of pig bone marrow, and their numbers were also increased by swine cytokine treatment. Swine IgG, but not B cells were detected in SCID recipients at 3 and 6 weeks following bone marrow transplantation, and declined over time, suggesting that mature B cells engrafted, but that de novo B lymphopoiesis did not occur in these mice. Thus, our study demonstrates that donor‐specific growth factors can help to overcome the physiologic barrier to xenogeneic hematopoiesis in the discordant pig to mouse species combination.
Quantitative evaluation of porcine endothelial cell antigens recognized by human natural antibodies: An analysis by Western blotting
Authors: Lin Shu S. , Parker William , Holzknecht Zoie E. , Platt Jeffrey L
Published: November 2008

Abstract: Xenoreactive natural antibodies recognize a series of glycoproteins in porcine endothelial cell membranes, the epitopes being Galα1–3Gal substitutions on those proteins. We recently identified the glycoprotein antigens as members of the integrin family, von Willebrand factor, and DM‐GRASP. The antibodies that react with these structures are adsorbed during perfusion of a porcine organ, indicating that these antigens may be the biologically relevant targets. To evaluate the relative importance of the glycoproteins as targets of xenoreactive natural antibodies, immunoreactive electrophoretic bands containing these glycoproteins were analyzed by photodensitometry. The relevance of these antigens in the recognition of endothelial cell antigens by xenoreactive natural antibodies was assessed by an analysis of the differences between antigens recognized by normal human serum and those recognized by human serum that had been depleted of xenoreactive natural antibodies. Depletion of xenoreactive natural antibodies was performed by adsorption of serum on cultured porcine aortic endothelial cell monolayers and by perfusion through a porcine kidney. The analysis revealed that greater than 91% of the antibodies binding to porcine cell surfaces are specific for antigens identified in porcine endothelial cell membrane extracts. Quantitative analysis of antigens recognized by affinity purified antibodies confirmed that integrins are indeed the primary xenogeneic targets recognized on Western blots of porcine aortic endothelial cell membranes.
Molecular cloning and characterization of the porcine CD 18 leukocyte adhesion molecule
Authors: Lee Jong‐Keuk , Schook Lawrence B. , Rutherford Mark S.
Published: November 2008

Abstract: Leukocyte adhesion molecules play an important role in regulating immunocyte trafficking into peripheral tissues. CD 18 is the common β‐chain of the β2‐integrin class of leukocyte adhesion molecules. Porcine CD 18 cDNA was cloned using reverse transcriptase‐polymerase chain reaction (RT‐PCR), subcloned, and sequenced (GenBank accession number U13941). The deduced 769 amino acid sequence for porcine CD18 contains a 22 amino acid signal sequence, a cysteine‐rich domain, and a 23 amino acid transmembrane domain. Porcine CD18 showed 79.3% cDNA sequence identity and 83.2% amino acid sequence identity with human CD 18. Northern blot analysis revealed that porcine CD 18 mRNA was expressed constitutively at high levels in freshly isolated alveolar macrophages, and levels declined approximately 50% over a 12 hr culture period. Peripheral blood cells and spleen cells expressed lower amounts of CD 18 mRNA. Anti‐human and anti‐canine CD 18 antibodies were tested for xeno‐reactivity against porcine CD18, and more than 62% freshly isolated unstimulated alveolar macrophages were stained with anti‐CD 18 antibodies. Porcine macrophage CD 18 transcript levels and cell surface expression detected by flow cytometry were not significantly altered following stimulation with LPS or human promflammatory cytokines, including interferon‐γ(IFN‐γ), interleukin‐α (IL‐1α), IL‐1β, tumor necrosis factor‐α (TNFα), and IL‐6. Thus, CD 18 gene expression by porcine alveolar macrophages appears not to be regulated by human proinflammatory cytokines. These reagents may be useful for studying the role of adhesion molecules in the immunobiology of porcine models of allo‐ and xenotransplantation
Discordant liver transplantation in the guinea pig to rat model does not lead to classical hyperacute rejection
Authors: Schraa Edo O. , Schotman Sylvia N. , Scheringa Marcel , Daha Mohamed R. , Marquet Richard L. , IJzermans Jan N.M.
Published: November 2008

Abstract: Discordant grafting, the best alternative for future transplantation, is hampered by hyperacute rejection (HAR). Yet, there might be a difference in susceptibility to HAR between organs. In allogeneic transplantation the liver is less sensitive to antibody mediated rejection. In order to investigate whether this might also occur in discordant xenotransplantation, we performed orthotopic liver transplantation (OLT) from Dunkin Hartley guinea pigs (GP) to Brown Norway rats. Five groups were studied. In group 1, untreated controls survived for 1.5 to 4.5 hr (n = 5). In order to investigate how long a recipient could survive without a functioning graft, animals in group 2 underwent total hepatectomy (tHx) with portal‐caval shunt, resulting in survival times ranging from 2 to 7 hr (n = 5). Antibody reduction by splenectomy (Spx) on day ‐5 (group 3) did not increase survival time (1 to 2 hr, n = 5). Complement depletion by cobra venom factor (CVF) prolonged the survival time up to 35 hr (n = 7, group 4). One animal lived for 4 days. The combined treatment of Spx and CVF resulted in similar survival times as following CVF alone, ranging from 2 hr to 6 days (n = 6, group 5). Surprisingly, none of the grafts in either of the groups showed classical signs of hyperacute rejection, like hemorrhage, edema, or obstruction of capillaries and veins as seen in the GP to rat heart transplantation model. Also liver enzyme parameters indicated no ongoing rejection. Immunohistochemistry revealed deposits of complement factors C1q, C3, and C6 on Kupffer cells but not on endothelial cells. These results indicate that, in this particular discordant model, the liver is not affected by the classical features of HAR. The beneficial effect of CVF on recipient survival therefore may rather be due to inhibition of a lethal secondary response evoked by the graft than to inhibition of HAR.
Xenogeneic bone marrow transplantation: I. Cloning, expression, and species specificity of porcine IL‐3 and granulocyte‐macrophage colony‐stimulating factor
Authors: Hawley Robert J. , Abraham Sonny , Akiyoshi Donna E. , Arduini Robert , Denaro Maria , Dickerson Matt , Meshalum Deborah H. , Monroy Rod L. , Schacter Bernice Z. , Rosa Margaret D.
Published: November 2008

Abstract: Establishment of mixed bone marrow chimerism has been used to induce tolerance to solid organ transplants in several allograft and xenograft models. The species specificity displayed by some important hematopoietic cytokines potentially limits the efficacy of this approach in pig‐to‐primate models. In order to examine the role porcine‐specific factors may play in the establishment of xenogeneic mixed bone marrow chimerism, we have cloned and heterologously expressed the genes encoding porcine IL‐3 and granulocyte‐macrophage colony‐stimulating factor, two myeloid growth factors previously shown to have significant species specificity. The purified porcine factors are demonstrated here to be potent stimulators of porcine bone marrow cell proliferation, but to have little or no effect on primate cells. The species specificity of these factors is reciprocal, in that the corresponding human cytokines have little activity I on porcine bone marrow cells.
Xenograft accommodation is accompanied by intragraft Th2 cytokines and vascular expression of protective genes
Authors: Mark Walter , Hechenleitner Paul , Candinas Daniel , Miyatake Tsukasa , Koyamada Nozomi , Margreiter R. , Hancock Wayne W. , Bach Fritz H.
Published: November 2008

Abstract: We have studied the accommodation (survival of an organ graft in the presence of anti‐graft antibodies and complement) of heterotopic Golden Syrian hamster heart xenografts transplanted to Lewis rat recipients. The rats were treated with cyclosporine A (15 mg/kg/day i.m.) for the duration of the experiment and for 11 days with cobra venom factor. This regimen resulted in long‐term xenograft survival in approximately 75% of cases. Analysis of endothelial cells (and smooth muscle cells) in long‐surviving grafts showed expression of “protective” genes: A20, Bcl‐xL, Bcl‐2, and hemoxygenase, which we define as genes that prevent endothelial cells from undergoing responses that might lead to graft rejection. Surviving xenografts were also associated with intragraft Th2 cytokine expression. Rejected grafts did not express the protective genes and had a Thl pattern of cytokine expression. These studies indicate a potential mechanism linking molecular and cellular responses to development of xenograft accommodation.
Conditions permitting short‐term engraftment of human T cells in RAG‐1 mutant mice
Authors: Sawada Tokihiko , Friedman Tony , Iacomini John
Published: November 2008

Abstract: The ability to reconstitute RAG‐1 deficient (R‐) mice with human peripheral blood cells was examined using four different host preparative regimens. Our results indicate that while untreated R‐ mice could be reconstituted with human cells, pre‐conditioning with either 5Gy whole body irradiation (WBI) or anti‐asialo GM1 rabbit anti‐serum led to an increase in the frequency of CD45+ human cells that could be detected in the circulation. Pre‐conditioning with both anti‐asialo GM1 and WBI led to a further increase in the frequency of circulating human cells in reconstituted R‐ mice. Human CD45+ cells were detected in the spleen and lymph nodes, but not the thymus of reconstituted mice pre‐conditioned with WBI and anti‐asialo GM1. Our results suggest that mouse NK cells and a limitation in physical space are limiting factors mediating resistance I to human cell engraftment in R‐ mice.
Risk factors of preterm delivery in HIV‐infected pregnant women receiving zidovudine for the prevention of perinatal HIV
Authors: Traisathit Patrinee , Mary Jean Yves , Le Cœur Sophie , Thantanarat Sudanee , Jungpichanvanich Sivaporn , Pornkitprasarn Witaya , Gomutbutra Vorapin , Matanasarawut Wanmanee , Wannapira Wiroj , Lallemant Marc
Published: November 2008

Aim:  Several studies have shown that preterm delivery, a primary cause of perinatal mortality and morbidity, is more frequent in HIV‐positive women. This study aimed to determine factors associated with prematurity in HIV‐infected women and identify risks for which specific interventions could be targeted.

Methods:  Data were prospectively collected in a clinical trial assessing the efficacy of different zidovudine prophylaxis durations for the prevention of perinatal HIV transmission in Thailand. Characteristics associated with prematurity – delivery before 37 weeks – were assessed using univariate and multivariate logistic regression and were subsequently used to identify subgroups of women at risk.

Results:  Among 979 women, independent prematurity risk factors were: viral load <3.5 or >4.5 log copies/mL; hemoglobin >11.5 g/dL; weight gain <0.25 kg/week; and body mass index <20 kg/m2. These factors allowed us to define four subgroups with an expected probability of prematurity increasing from 3% to 30%. The two subgroups with the highest expected probability of prematurity were considered to be ‘at risk’ as opposed to the two lowest (odds ratio = 2.6, 95% confidence interval: 1.7–4.0) and the sensitivity and specificity of the prediction were 51% and 71%, respectively.

Conclusion:  In this study, four risk factors of preterm delivery were identified allowing the identification of subgroups at increasing risk of prematurity. Adequate nutrition and the provision of highly active antiretroviral therapy during pregnancy as recommended by the World Health Organization for the prevention of perinatal transmission for immunocompromised women in resource‐constrained countries may reduce the risk of premature delivery.
The assessment of the gestational sac diameter, crown–rump length, progesterone and fetal heart rate measurements at the 10th gestational week to predict the spontaneous abortion risk
Authors: Altay M. Metin , Yaz Hakan , Haberal Ali
Published: November 2008

Aim:  The assessment of the first trimester ultrasonographic and progesterone measurements to predict spontaneous abortion risk.

Methods:  Ninety‐nine women at the 10th week of pregnancy were included in this prospective study. Their ages, progesterone (P) levels, mean gestational sac diameters (MGSD), crown–rump lengths (CRL), MGSD–CRL measurements and fetal heart rates (FHR) were recorded. These variables were compared by abortion status.

Results:  Patients were followed up until the 20th weeks, and 8 (8.08%) aborted. We evaluated the variables by receiver operator characteristic curve to predict abortion. Only the areas under the curve for P levels (0.29) and for MGSD–CRL (0.16) were statistically significant. We also made logistic regression analysis to predict abortion. P level and FHR were statistically significant (P < 0.01) when the threshold value was 50%. Negative predictive value of the model was 98.9%, and positive predictive value was 50%. Overall, this model can correctly classify 94.9% of the groups. We determined threshold values for MGSD–CRL (≥10 mm) and P (≥25 ng/mL) to predict abortion, but not for FHR. Interestingly, 14 patients with FHR ≥ 175 beats/min did not abort. For the MGSD–CRL threshold, we can predict that the pregnancy will continue with 95.78% probability, with 67% sensitivity and 89% specificity. For the P threshold, the pregnancy will continue with 97.85% probability, with 80% sensitivity and 80% specificity.

Conclusion:  MGSD–CRL and P could predict patients with low abortion risk. However, at the 10th week of pregnancy, FHR ≥ 175 beats/min should be evaluated for this purpose by future studies with larger sample sizes.
Prognostic factor on optimal debulking surgery by maximum effort for stage IIIC epithelial ovarian cancer
Authors: Terauchi Fumitoshi , Nishi Hirotaka , Moritake Tetsuya , Kobayashi Yukari , Nagashima Takeo , Onodera Takamoto , Fujito Atsuya , Nakayama Daiei , Isaka Keiichi
Published: November 2008

Objectives:  The aim of this study was to assess the prognostic factor of radical surgery in patients with stage IIIc ovarian cancer.

Study design:  Fifty‐two patients were subjected to the study. The complete resection or optimal primary cytoreductive surgery (OPCS) was set as the maximum effort, and the accomplishment rate and prognosis were assessed. In addition, the poor prognosis cases among the OPCS‐accomplished were evaluated with several factors based on univariate and multivariate analyses.

Results:  The OPCS accomplishment rate was 84.6%. A worse prognosis was obtained in the more‐than‐4‐weeks‐delayed postoperative chemotherapy group, assessing poor‐outcome cases in the OPCS group. A case that required more than three colon resections was the significant factor for the delay of postoperative chemotherapy.

Conclusions:  OPCS should be performed with maximum effort to improve the prognosis of stage IIIc ovarian cancer. We should avoid any delay in starting postoperative chemotherapy. In cases that require more than three colon resections, it seems that ‘perioperative management’ should be reconsidered and that priority should be given to postoperative management so that chemotherapy can be started soon after the operation.
Decreased bone mineral density of femur in patients with cervical cancer
Authors: Lee Seung H. , Ku Chun H. , Lee Kwang B. , Shin Jin W. , Park Chan Y.
Published: November 2008

Aims:  We compared the bone mineral density (BMD) of spinal bone and the femur between patients with cervical cancer and a control group.

Methods:  We retrospectively analyzed the BMD of spinal bone and the femur in 40 patients with cervical cancer and 72 control women. The control women were patients treated with surgery for benign disease.

Results:  Age, height, bodyweight and body mass index were not significantly different between the two groups. Total femoral BMD in patients with cervical cancer was significantly lower (P = 0.006) than that of control women.

In multiple regression analysis, the bodyweight of patients with cervical cancer was a statistically significant predictor positively correlated with the BMD of the total femur.

Conclusion:  The results suggest that patients with cervical cancer have low bone mass, especially in the femur, and an increased risk of developing osteoporosis.
Wage Dispersion and Equilibrium Search Models: Some Evidence from Italy
Authors: Sulis Giovanni
Published: November 2008

This paper provides a structural estimation of an equilibrium search model with on‐the‐job search and heterogeneity in firms' productivities using a sample of Italian male workers. Results indicate that arrival rates of offers for workers are higher when unemployed than when employed and firms exploit their monopsony power when setting wages. As a result, workers earn far less than their marginal product. The model is then used to study regional labour market differentials in Italy. Wide variation in frictional transition parameters across areas helps to explain persistent unemployment and wage differentials.
THE WILD AND CROOKED TREE: BARTH, FISH, AND INTERPRETIVE COMMUNITIES
Authors: SAYE SCOTT C.
Published: November 2008

God the Spirit by Michael Welker

Karl Barth's Critically Realistic Dialectical Theology: Its Genesis and Development 1909‐1936 by Bruce L. McCormack

God Owes Us Nothing: A Brief Remark on Pascal's Religion and on the Spirit of Jansenism by Leszek Kolakowski

The Gift of Death by Jacques Derrida, trans. David Wills

Desiring Theology by Charles E. Winquist

Postmodern Theologies. The Challenge of Religious Diversity by Terrence W. Tilley, with others
Paraneoplastic neurological syndromes in patients with carcinoid
Authors: Tschernatsch M. , Dierkes C. , Gerriets T. , Hosch J. , Stolz E. , Kaps M. , Krasenbrink I. , Claus D. , Blaes F.
Published: November 2008

Background:  Paraneoplastic neurological syndromes (PNS) are mainly associated with small‐cell lung cancer, gynaecological tumours and lymphomas. Few studies report the association of neurological syndromes with a carcinoid, the majority being a serotonin‐related myopathy. We report four patients with a PNS associated with carcinoid.

Patients and results:  The clinical syndromes were sensory neuropathy, limbic encephalitis, myelopathy and brain stem encephalitis. Two patients had antineuronal autoantibodies (one anti‐Hu, one anti‐Yo), one patient had antinuclear antibodies, and one patient had no autoantibodies. For two of the carcinoids, expression of HuD in the tumour could be demonstrated.

Conclusion:  This study demonstrates that carcinoids can also be associated with classical antineuronal antibody‐associated PNS.
Is early‐onset clinically different from late‐onset frontotemporal dementia?
Authors: Borroni B. , Agosti C. , Bellelli G. , Padovani A.
Published: November 2008

Background and purpose:  Frontotemporal dementia (FTD) is the second most common neurodegenerative dementia in the young age after Alzheimer disease. Recent improvement in diagnostic assessment suggests that it is more common than previously, although with a great heterogeneity in clinical presentation. The different clinical patterns related to age of disease onset in behavioural variant FTD (bvFTD) have been fairly studied. Aim of the study was to evaluate whether age at disease onset modulate the heterogeneity of either cognitive impairment or behavioural disturbances in patients affected by bvFTD.

Methods:  One hundred and thirty‐four patients with bvFTD entered the study. Age at onset and demographic characteristics were carefully recorded. Each patient underwent a wide neuropsychological and behavioural standardized assessment, as well as a brain SPECT perfusion imaging study.

Results:  Behavioural variant FTD were subdivided into four groups according to the age at onset. The four quartile groups did not differ for demographic characteristics and family history for dementia. Global cognitive impairment as well as analysis of the different cognitive domains and behavioural patterns were comparable.

Conclusions:  These findings provide evidence that the clinical heterogeneity of bvFTD is not explained by age at disease onset. Further studies are needed.
Functional transcranial Doppler assessment of cerebral blood flow velocities changes during attention tasks
Authors: Matteis M. , Bivona U. , Catani S. , Pasqualetti P. , Formisano R. , Vernieri F. , Troisi E. , Caltagirone C. , Silvestrini M.
Published: November 2008

Background and Purpose:  Aim of our study was to evaluate cerebral hemodynamic changes during performance of attention tasks and to correlate them with reaction time (RT) and percentage of right answers.

Methods:  Mean flow velocity (MFV) in middle cerebral arteries was monitored in 30 subjects by transcranial Doppler during tonic alertness, phasic alertness, focused and divided attention tasks.

Results:  Mean flow velocity increase was significantly higher during divided attention with respect to other tasks (P < .001). MFV increase was higher in the right than in the left side (P < .001). Asymmetry during attention tasks resulted significantly higher than that observed in tonic alertness condition. RT was increased during focused attention tasks (P < .001 vs. both alert tasks), with further increase during divided attention tasks (P < .001 vs. focused attention task). RT was inversely related to MFV increase only during tonic alertness (P = 0.012 for left side; P = 0.008 for right side). During the divided attention tasks, an association was found between MFV increase and correct answers (r = 0.39, P = 0.033).

Conclusions:  These data show a relationship between RT, correct answers and changes in blood flow velocity and suggest that this method of cerebral blood flow investigation could be a useful approach during assessment of patients with attention deficit.
Report of the Task Force on pre‐graduate education in Europe of the education committee of the European Federation of Neurological Societies Composition of the task force of the education committee on pre‐graduate education
Authors: Lopes Lima J. M. , Mesec A. , Wilkinson I. M. S. , Wiles C. M. , Gilhus N. E. , Zimprich F. , Alekseenko Y. V. , Grisold W.
Published: November 2008

Background and purpose:  The demographical evolution and the technological revolution seen in the last decades, in developed countries, have dramatically changed the practice of Neurology. However, the academic curriculum in many medical schools has not been updated accordingly over many of the European Countries. The Education Committee of the European Federation of Neurological Societies (EFNS) implemented in 2000 a Task Force on pre‐graduate education trying to give guidelines to adequate pre‐graduate education to the present status.

Methods and discussion:  Based on the results of two questionnaires, the first sent to the delegates of the EFNS and to the delegates of the European Board of Neurology, and the second answered by the Task Force members themselves, this paper describes the Task Force recommendations aimed to improve Neurology Education in the Medical Schools. These recommendations are also discussed with the analyses of the current bibliography available.
Environmental gradients explaining the prevalence and intensity of infection with the amphibian chytrid fungus: the host's perspective
Authors: Rödder D. , Veith M. , Lötters S.
Published: November 2008

Chydridiomycosis is an infectious emerging disease in amphibians that has been directly linked to mass mortality, drastic population decline and extinction. The understanding of the factors limiting the distribution and the abundance of its biological agent, the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd ), is still limited. It has been suggested that climate plays a key role. A recent study conducted infection surveys at 31 lowland sites on the Australian East coast and searched for climatic variables explaining Bd prevalence and intensity in Stony creek frogs Litoria lesueuri (complex). A link between the prevalence of infections and latitude was advocated, exclusively focusing on the pathogen. Beyond this, the prevalence and intensity of Bd infection may also depend on the climatic suitability of a given site for the amphibian host. Herein, we extend the previous study using a set of long‐term bioclimatic variables and assess climatic suitability for Stony creek frogs at the sites previously studied for Bd. We ran a Climatic Envelope Model for our target amphibian based on those variables with the most explanatory power for prevalence and intensity, thus representing the link between climatic suitability for both the pathogen and the host. Our findings allow the hypothesis that there exists a significant correlation between climatic suitability for Stony creek frogs at the previously studied sites and latitude. At the same time, this was congruent with the latitudinal gradient of the number of zoospores per frog.
CGG‐repeat length and neuropathological and molecular correlates in a mouse model for fragile X‐associated tremor/ataxia syndrome
Authors: Brouwer Judith R. , Huizer Karin , Severijnen Lies‐Anne , Hukema Renate K. , Berman Robert F. , Oostra Ben A. , Willemsen Rob
Published: November 2008

The 5′untranslated region (UTR) of the FMR1 gene contains a CGG‐repeat, which may become unstable upon transmission to the next generation. When repeat length exceeds 200, the FMR1 gene generally undergoes methylation‐mediated transcriptional silencing. The subsequent absence of the gene product Fragile X Mental Retardation Protein (FMRP)causes the mental retardation seen in fragile X patients. A CGG‐repeat length between 55 and 200 trinucleotides has been termed the premutation (PM). Predominantly elderly male PM carriers are at risk of developing a progressive neurodegenerative disorder: fragile X‐associated tremor/ataxia syndrome (FXTAS). All PM carriers have elevated FMR1 mRNA levels, in spite of slightly decreased FMRP levels. The presence of intranuclear ubiquitin‐positive inclusions in many brain regions is a neuropathological hallmark of FXTAS. Studies in humans attempting to correlate neuropathological outcomes with molecular measures are difficult because of the limited availability of tissue. Therefore, we have used the expanded CGG‐repeat knock‐in mouse model of FXTAS to examine the relationship between the molecular and neuropathological parameters in brain. We present Fmr1 mRNA and Fmrp levels and the presence of intranuclear inclusions at different repeat lengths. Contrary to existing hypotheses, our results suggest that inclusion formation may not depend on the elevation per se of Fmr1 transcript levels in aged CGG mice.
Odorant receptor (OR) gene choice is biased and non‐clonal in two olfactory placode cell lines, and OR RNA is nuclear prior to differentiation of these lines
Authors: Pathak Nidhi , Johnson Paul , Getman Michael , Lane Robert P.
Published: November 2008

We have investigated two clonal mouse olfactory placode (OP) cell lines as a model system for studying endogenous odorant receptor (OR) regulation. Both lines can be differentiated into bipolar neurons with transcriptional profiles consistent with mature sensory neurons. We show that single cells exhibit monogenic OR expression like sensory neurons in vivo. Monogenic OR expression is established in undifferentiated cells and persists through differentiation, but OR gene choice is not a clonal property of either cell line. Interestingly, OR RNA shifts from predominantly nuclear to cytoplasma during differentiation of both cell lines. Finally, our data indicate that a restricted subset of OR genes and OR clusters are over‐represented in cell populations, suggesting either a pre‐existing intrinsic bias in OP founder cells or extrinsic influences arising from culture conditions.
Vision and hearing impairments and their associations with falling and loss of instrumental activities in daily living in acute hospitalized older persons in five Nordic hospitals
Authors: Grue Else Vengnes , Ranhoff Anette Hylen , Noro Anja , Finne‐Soveri Harriet , Jensdóttir Anna Birna , Ljunggren Gunnar , Bucht Gösta , Björnson Leif Jan , Jonsén Elisabeth , Schroll Marianne , Jónsson Palmi V.
Published: November 2008

Background:  Many older people believe sensory problems are inevitably, a part of growing old, and avoid assessment and help. Such problems are often also overlooked by health professionals. The aim of this study was to find the prevalence of hearing and vision impairment and their associations with loss of instrumental activities in daily living (IADL) and risk of falling in patients aged 75 years or older, admitted to a medical ward in an acute hospital in each of the five Nordic countries.

Method:  The Minimum Data Set for Acute Care was used for data collection in 770 patients. Premorbid data, admission data and history of falls over 3 months were obtained on admission by interview and observation. Hearing impairment was present if the patient required a quiet setting to be able to hear normal speech. Vision impairment was defined as unable to read regular print in a newspaper.

Results:  Bivariate and logistic regression analyses were performed. Forty‐eight per cent of the patients had a hearing impairment, 32.3% had vision impairment and 20.1% had both. Hearing impairment was associated with falling but not in the logistic regression model. Hearing and vision impairment were associated with loss of IADL but only combined impairment was independently.

Conclusion:  Hearing and vision impairments were frequent among older patients in the medical wards. Falling was associated with hearing loss and IADL loss with hearing, vision and combined impairments. Sensory loss was also associated with fear of falling. It is recommended routinely to screen sensory functions in older patients in a medical setting. Intervention studies are needed to determine whether improvements in hearing and vision can prevent falls and further loss of function in this patient population.
CHEMICAL–MINERALOGICAL ANALYSES AND MICROSTRUCTURAL STUDIES OF PREHISTORIC POTTERY FROM RAHMATABAD, SOUTH‐WEST IRAN*
Authors: MARGHUSSIAN A. K. , FAZELI H. , SARPOOLAKY H.
Published: November 2008

A series of prehistoric pottery samples excavated from Rahmatabad, south‐west Iran, were investigated using XRF and XRD analyses to determine their chemical and mineralogical compositions. The sample microstructures were also studied by SEM/EDX. The relative similarity of compositions, the fine, dense and homogeneous microstructures and the presence of high‐temperature phases such as diopside and mullite showed the use of high firing temperatures, in the range 950–1050°C. This, along with the homogeneity in shape, decoration and size ranges of the ware, all indicate the adoption of specialized pottery‐making techniques by the potters of Rahmatabad in the fifth to fourth millennia bc.
Sustainability assessment of national rural water supply program in Tanzania
Authors: Giné Ricard , Pérez‐Foguet Agustí
Published: November 2008

Sustainability of rural water supply programs in developing countries is still an elusive goal. It is widely accepted that, as a rule, they have failed to deliver benefits to society in the long run. Emphasis has frequently been placed on the short‐term activities. Fast production of new schemes is thus a common strategy, prioritizing the engineering component, while sidestepping social and participatory issues and community empowerment.

In 2006, the Government of Tanzania launched a national program to meet water sector targets set out in the Millennium Development Goals by the year 2015. In this study we evaluate key features of the program on a sustained basis. There is evidence that the Government is promoting more sustained facilities, focusing on cost recovery and on ‘decentralization by devolution’. Nevertheless, there are several shortcomings which threaten the long‐term functionality of the infrastructure that has to be built. In light of the implementation of the program, and based on the outputs of its pilot phase, we review the factors that can determine its sustainability.
Long‐Term Clinical and Hemodynamic Evaluation of the Ionescu‐Shiley Pericardial Xenograft Heart Valve
Authors: Ionescu Marian I. , Tandon Anand P.
Published: November 2008

Pericardial xenograft heart valves have been used in 469 patients for single or multiple valve replacement. Early in the series, valves were made in‐house, but since May 1976, valves have been made by Shiley Laboratories, Inc. During the eight‐year observation period, there were 7% early and 7.9% late deaths. Although no anti‐coagulants were used on a long‐term basis, there were only eight mild embolic episodes. Preoperatively, 56–98% of all patients were in class III or IV of the NYHA classification; postoperatively, all surviving patients have been found to have improved by at least one classification.
Long‐Term Performance of Homograft and Autograft Valves
Authors: Bodnar Endre , Wain William H. , Martelli Valentino , Ross Donald N.
Published: November 2008

Five hundred and eighty homograft valves have been inserted into the aortic position as isolated valve replacements, and followed up for 7–14 years. After ten years 90% of frozen homografts, 80% of autografts and 70% of freeze‐dried homografts were free of valve‐related death. There was only one embolism reported giving an incidence of one embolism per 143,928 patient months. Degeneration occurred in 14% of the autografts, in 30% of the freeze dried and in 60% of the frozen homografts after ten years. Eighty per cent of the fresh homografts have been free of degeneration after seven years, and 54% of freeze‐dried valves have been free of degeneration after 14 years. Long‐term performance of homograft and autograft valves in the aortic positon is comparable to that of any prosthetic or bioprosthetic valve. In addition, they are non‐thrombogenic and excellent in terms of patient survival.
Clinical Results of Valve Replacement by the Starr‐Edwards Prosthesis
Authors: Stolf N. A. G. , Dallan L. A. , Puig L. B. , Tsuzuki S. , Lavitola P. , Pillegi F. , Bittencourt D. , Verginelli G. , Zerbini E. J.
Published: November 2008

Heart valve replacement has initiated special research efforts and has led to debate among surgeons from different surgical services. It is in this area of cardiac surgery that complications are frequent. This paper is a summarized review of the problems related to valve replacement by the Starr‐Edwards prosthesis at the University of São Paulo Medical School Heart Institute. It describes the difficulties which led the authors to abandon its use in 1971. Clinical experience is from July 1958 to January 1974.
Multifactorial Evaluation of Hernofiltration Therapy in Comparison with Conventional Hemodialysis
Authors: Nakagawa Seinosuke
Published: November 2008

In order to ascertain if the potential benefits claimed for hemofiltration (HF) are supportable, chronic thrice‐weekly HF therapy has been assessed in a group of nine uremic patients who had previously been stablized on conventional hemodialysis (HD) for a mean of 17.8 months at a frequency of 3 × 5 hours/week. Changes between the termination of HD (= initiation of HF) and the last three months were observed in multifactorial parameters.

No significant differences were observed in any parameter except the frequency of hypotensive episodes and the pretreatment levels of conventional waste metabolites.

The latter were higher on HF than HD and the frequency of hypotension, 2% in HF, was less than the 8% frequency observed in HD, despite much larger body weight reductions per HF treatment. Also, the effects of HF on hypertension and hyperlipidemia were not significantly better than observed on HD therapy. Our preliminary conclusions are that HF is superior to HD in both the ease and safety of fluid removal and there is virtual elimination of the disequilibrium syndrome. However, HF offers no other obvious advantages over conventional hemodialysis therapy.
Simultaneous Hernofiltration/ Hernodialysis (HF/HD): Short‐ and Long‐Term Tolerance. Introduction of a System for Automatic Fluid Replacement
Authors: Leber Heinrich‐W. , Wizemann Volker , Techert Franz
Published: November 2008

Data are presented concerning our experiences with simultaneous hemofiltration and hemodialysis (HF/HD) in uremic patients. Ten randomly selected patients have been treated for two and a half to three yeare with either conventional hemodialysis (HD, 3×4 hour/week, 1.4 m2 surface area Cuprophan dialyzer) or HF/HD (RP‐6, 3×3 hours/week). No differences could be detected with regard to the blood chemistry or the blood pressure between the two groups of patients. During HF/HD the well‐being of the patients was better than during HD, which can be attributed to a greater stability of the blood pressure and of the serum osmolarity and to a decrease of the intraocular pressure during treatment. An apparatus is described which is in use enabling the automatic replacement of the required substitution fluid. With regard to the performance and the tolerance, HF/HD is comparable to hemofiltration, but the treatment sessions are shorter.
Uremic Neurotoxin in the Middle Molecular Weight Range
Authors: Man N.K. , Cueille G. , Zingraff J. , Boudet J. , Sausse A. , Funck‐Brentano J.‐L.
Published: November 2008

Among the middle molecule fractions obtained by high performance gel chromatography on Sephadex G‐15 combined with gradient ion exchange chromatography on DEAE Sephadex A‐25 from plasma ultrafiltrates of six polyneuropathic patients, only peak b4–2 was at a significantly higher concentration than that obtained from uremic patients with neuropathy. Purification of the b4–2 solute allows its quantitative determination in biological fluids. The b4–2 plasma concentrations are 1 mg/L in healthy subjects (n=30), 4.6 ± 0.2 mg/L in uremic patients (n=67) and 13–19 mg/L in six polyneuropathic patients. The 24‐hr urinary excretion is 13 ± 1 mg. The weekly removal rates in hemofiltration or in hemodialysis, using high permeability membrane three times a week, are 38–40 mg. In an in vitro sural nerve test for the evaluation of middle molecule neurotoxicity, the b4–2 solute exhibits a neurotoxic effect at concentrations similar to those found in plasma of neuropathic patients. Preliminary results of an attempt to identify the neurotoxin indicate that it is an acid‐polyo derivative.
The Effect of Coumadin Upon Thrombus Forming on Foreign Surfaces
Authors: Madras Peter N. , Thomson Chiquita L. , Johnson Webster R.
Published: November 2008

Experience with the Stagnation Point Flow Experiment has revealed the earliest microscopic events surrounding thrombus inception and growth on foreign surfaces in a perfectly defined flow field. Using 40 and 80 × magnification, the effects of Coumadin upon these events was studied. These events include leukocyte adherence, fibrin deposition and platelet aggregation, deviation of flow streamlines around these aggregates, and subsequent downstream thrombus growth. Surface density of leukocytes was measured as a function of time and shear, and served as an index of the quantity of thrombus on the surface, which in turn, allowed direct comparisons of thrombus growth rate between experiments. Coumadin decreases the adhesive force between leukocytes or thrombi and the foreign surface. Emboli are more frequent with Caumadin, but are smaller. Thrombus inception is not altered. These results suggest that clinical benefit obtained from use of Coumadin derives from reduction in size of emboli.
Residual Formaldehyde in Dialyzers: Quantity, Location, and the Effect of Different Methods of Rinsing
Authors: Lewis K. J. , Ward M. K. , Kerr D. N. S.
Published: November 2008

When formalin‐sterilized dialyzers were rinsed by our standard technique (similar to that used in many other dialysis centres) undesirable concentrations of formaldehyde were found in the dialyzers at the start of dialysis. When the technique was modified by passing part of the saline through the blood compartment immediately before connection and discarding the saline left in the dialyzer at the time of connection, the concentration of formaldehyde infused into the patient fell below 2 μg/ml. However, the dialyzers still contained up to 13 mg of formaldehyde which leached slowly from the dialyzer during simulated dialysis. Some residual formaldehyde was found in several components of the dialyzer but the great majority was contained in the cellulose membrane.
Effect of Moisture on and Kinetic Features of the Ultrafiltration Rate of Dialysis Membrane
Authors: Sato Hiroshi , Kidaka Teruhisa
Published: November 2008

The kinetic features of ultrafiltration of cellulose dialysis membrane stored under various humidity and temperature conditions were studied to obtain basic information on shelf‐life characteristics of dialyzers. The ultrafiltration rate (UFR) decreased with time and the UFR‐time curve suggested that the UFR would approach a certain equilibrium value. This phenomenon could be simulated well by the following equation: UFR = a.b.t/(1 + a.t) + c, where a, b, and c are constants and t is time. The effect of moisture adsorption onto the membrane on the UFR is discussed. A hypothesis is that in the amorphous region of cellulose, adsorbed water molecules would serve as molecular crosslinks through hydrogen bonding, and as this would reduce size of fine pores in the amorphous region, the UFR decreases.
Continuous Enrichment of Albumin in Relation to Globulins in Plasma
Authors: Shettigar U. R. , Mann H. , Gressner A.
Published: November 2008

This in vitro study deals with the problem of continuous separation of albumin from globulins in patient's plasma and reinfusion of the useful components of the plasma to the patient as the substitution fluid during a plasma exchange (PE) treatment. A cascade filtration system is developed to generate continuously two plasma fractions, one rich in globulins and the other rich in albumins, using two filters (H1P100 filter with a molecular weight cutoff 100,000 and Diafilter 20 with a molecular weight cutoff 30,000). For example, the system is able to increase the albumin/globulin ratio of plasma from 0.42 to 1.98, and the albumin concentration in the secondary plasma fraction is about seven times higher than that in the primary plasma fraction. This system is expected to be clinically useful in eliminating the side effects inherent in the usage of any other substitution fluid during a PE treatment.
The TM Bubble Oxygenator: Development and Clinical Application
Authors: Tamiya Tatsuo , Kitagawa Shiroshi , Yamashiro Toshiyuki , Takemasa Atsuo , Sadamitsu Takeo , Nishizawa Tadashi , Suzuki Ichiro , Shiramatsu Kazuyasu
Published: November 2008

A bubble oxygenator (the TM or the OCVC oxygenator) has been produced with development efforts focused particularly on reduction of the nonphysiological characteristics of this type of oxygenator. The structural features of the apparatus are: (1) a reduction to the minimum of adequate priming volume, (2) an oxygen disperser designed to ensure evenly dispersed, uniform‐sized bubbles, (3) a volume‐control system for the oxygenating chamber (the OCVC system) based on extensive experimental oxygenation studies, and (4) an integrated double microfilter of the gravity‐drainage type. Clinical features are: (1) ease of operation in perfusion, (2) reduction in hemolysis and postoperative blood loss, and (3) fewer complications associated with microemboli. Clinical use on over 200 infants and children proved generally very satisfactory. The background of its development is briefly described as are future modification plans.