Comparison of Fluid Types for Resuscitation in Acute Hemorrhagic Shock and Evaluation of Gastric Luminal and Transcutaneous P co 2 in Leghorn Chickens

The objective of this study was to compare the effects of 3 different fluid types for resuscitation after experimentally induced hemorrhagic shock in anesthetized chickens and to evaluate partial pressures of carbon dioxide measured in arterial blood (Paco2), with a transcutaneous monitor (TcPco2), with a gastric intraluminal monitor (GiPco2), and by end tidal measurements (Etco2) under stable conditions and after induced hemorrhagic shock. Hemorrhagic shock was induced in 40 white leghorn chickens by removing 50% of blood volume by phlebotomy under general anesthesia. Birds were divided into 4 groups: untreated (control group) and treated with intravenous hetastarch (haes group), with a hemoglobin-based oxygen carrier (hemospan group), or by autotransfusion (blood group). Respiratory rates, heart rates, and systolic arterial blood pressure (SAP) were compared at 8 time points (baseline [T0]; at the loss of 10% [T10%], 20% [T20%], 30% [T30%], 40% [T40%], and 50% [T50%] of blood volume; at the end of resuscitation [RES]; and at the end of anesthesia [END]). Packed cell volume (PCV) and blood hemoglobin content were compared at 6 time points (T0, T50%, RES, and 1, 3, and 7 days after induced hemorrhagic shock). Measurements of Paco2, TcPco2, GiPco2, and Etco2 were evaluated at 2 time points (T0 and T50%), and venous lactic acid concentrations were evaluated at 3 time points (T0, T50%, and END). No significant differences were found in mortality, respiratory rate, heart rate, PCV, or hemoglobin values among the 4 groups. Birds given fluid resuscitation had significantly higher SAPs after fluid administration than did birds in the control group. In all groups, PCV and hemoglobin concentrations began to rise by day 3 after phlebotomy, and baseline values were reached 7 days after blood removal. At T0, TcPco2 did not differ significantly from Paco2, but GiPco2 and Etco2 differed significantly from Paco2. After hemorrhagic shock, GiPco2 and TcPco2 differed significantly from Paco2. The TcPco2 or GiPco2 values did not differ significantly at any time point in birds that survived or died in any of the groups and across all groups. These results showed no difference in mortality in leghorn chickens treated with fluid resuscitation after hemorrhagic shock and that the PCV and hemoglobin concentrations increased by 3 days after acute hemorrhage with or without treatment. The different CO2 measurements document changes in CO2-values consistent with poor perfusion and may prove useful for serial evaluation of responses to shock and shock treatment.

High prevalence of hereditary thrombotic thrombocytopenic purpura in Central Norway: from clinical observation to evidence.

BACKGROUND Hereditary thrombotic thrombocytopenic purpura (TTP) caused by ADAMTS13 mutations is a rare, but serious condition. The prevalence is unknown, but seems to be high in Norway. OBJECTIVES To identify all patients with hereditary TTP in Central Norway and to investigate the prevalence of hereditary TTP and the population frequencies of two common ADAMTS13 mutations. Patients/Methods Patients were identified in a cross-sectional study within Central Norway Health Region by means of three different search strategies. Frequencies of ADAMTS13 mutations, c.4143_4144dupA and c.3178 C>T (p.R1060W) were investigated in a population-based cohort (500 alleles) and in healthy blood donors (2104 alleles) by taking advantage of the close neighbourhood of the ADAMTS13 and ABO blood group gene loci. The observed prevalence of hereditary TTP was compared to the rates of ADAMTS13 mutation carriers in different geographical regions. RESULTS We identified 11 families with hereditary TTP in Central Norway during the 10-year study period. The prevalence of hereditary TTP in Central Norway was 16.7 x 10(-6) . The most prevalent mutation was c.4143_4144dupA, accounting for two thirds of disease causing alleles among patients and having an allelic frequency of 0.33% in the Central, 0.10% in the Western, and 0.04% in the Southeastern Norwegian population. The allelic frequency of c.3178 C>T (p.R1060W) in the population was even higher (0.3-1%), but this mutation was infrequent among patients, with no homozygous cases. CONCLUSIONS We found a high prevalence of hereditary TTP in Central Norway and an apparently different penetrance of ADAMTS13 mutations. This article is protected by copyright. All rights reserved.

Zonal playfield attributes – A stochastic approach to subjective passing affordances in football

Introduction: According to the ecological view, coordination establishes byvirtueof social context. Affordances thought of as situational opportunities to interact are assumed to represent the guiding principles underlying decisions involved in interpersonal coordination. It’s generally agreed that affordances are not an objective part of the (social) environment but that they depend on the constructive perception of involved subjects. Theory and empirical data hold that cognitive operations enabling domain-specific efficacy beliefs are involved in the perception of affordances. The aim of the present study was to test the effects of these cognitive concepts in the subjective construction of local affordances and their influence on decision making in football. Methods: 71 football players (M = 24.3 years, SD = 3.3, 21 % women) from different divisions participated in the study. Participants were presented scenarios of offensive game situations. They were asked to take the perspective of the person on the ball and to indicate where they would pass the ball from within each situation. The participants stated their decisions in two conditions with different game score (1:0 vs. 0:1). The playing fields of all scenarios were then divided into ten zones. For each zone, participants were asked to rate their confidence in being able to pass the ball there (self-efficacy), the likelihood of the group staying in ball possession if the ball were passed into the zone (group-efficacy I), the likelihood of the ball being covered safely by a team member (pass control / group-efficacy II), and whether a pass would establish a better initial position to attack the opponents’ goal (offensive convenience). Answers were reported on visual analog scales ranging from 1 to 10. Data were analyzed specifying general linear models for binomially distributed data (Mplus). Maximum likelihood with non-normality robust standard errors was chosen to estimate parameters. Results: Analyses showed that zone- and domain-specific efficacy beliefs significantly affected passing decisions. Because of collinearity with self-efficacy and group-efficacy I, group-efficacy II was excluded from the models to ease interpretation of the results. Generally, zones with high values in the subjective ratings had a higher probability to be chosen as passing destination (βself-efficacy = 0.133, p < .001, OR = 1.142; βgroup-efficacy I = 0.128, p < .001, OR = 1.137; βoffensive convenience = 0.057, p < .01, OR = 1.059). There were, however, characteristic differences in the two score conditions. While group-efficacy I was the only significant predictor in condition 1 (βgroup-efficacy I = 0.379, p < .001), only self-efficacy and offensive convenience contributed to passing decisions in condition 2 (βself-efficacy = 0.135, p < .01; βoffensive convenience = 0.120, p < .001). Discussion: The results indicate that subjectively distinct attributes projected to playfield zones affect passing decisions. The study proposes a probabilistic alternative to Lewin’s (1951) hodological and deterministic field theory and enables insight into how dimensions of the psychological landscape afford passing behavior. Being part of a team, this psychological landscape is not only constituted by probabilities that refer to the potential and consequences of individual behavior, but also to that of the group system of which individuals are part of. Hence, in regulating action decisions in group settings, informers are extended to aspects referring to the group-level. References: Lewin, K. (1951). In D. Cartwright (Ed.), Field theory in social sciences: Selected theoretical papers by Kurt Lewin. New York: Harper & Brothers.

Racial Disparities in Access to and Outcomes of Kidney Transplantation in Children, Adolescents, and Young Adults: Results From the ESPN/ERA-EDTA (European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association) Registry.

BACKGROUND Racial disparities in kidney transplantation in children have been found in the United States, but have not been studied before in Europe. STUDY DESIGN Cohort study. SETTING & PARTICIPANTS Data were derived from the ESPN/ERA-EDTA Registry, an international pediatric renal registry collecting data from 36 European countries. This analysis included 1,134 young patients (aged ≤19 years) from 8 medium- to high-income countries who initiated renal replacement therapy (RRT) in 2006 to 2012. FACTOR Racial background. OUTCOMES & MEASUREMENTS Differences between racial groups in access to kidney transplantation, transplant survival, and overall survival on RRT were examined using Cox regression analysis while adjusting for age at RRT initiation, sex, and country of residence. RESULTS 868 (76.5%) patients were white; 59 (5.2%), black; 116 (10.2%), Asian; and 91 (8.0%), from other racial groups. After a median follow-up of 2.8 (range, 0.1-3.0) years, we found that black (HR, 0.49; 95% CI, 0.34-0.72) and Asian (HR, 0.54; 95% CI, 0.41-0.71) patients were less likely to receive a kidney transplant than white patients. These disparities persisted after adjustment for primary renal disease. Transplant survival rates were similar across racial groups. Asian patients had higher overall mortality risk on RRT compared with white patients (HR, 2.50; 95% CI, 1.14-5.49). Adjustment for primary kidney disease reduced the effect of Asian background, suggesting that part of the association may be explained by differences in the underlying kidney disease between racial groups. LIMITATIONS No data for socioeconomic status, blood group, and HLA profile. CONCLUSIONS We believe this is the first study examining racial differences in access to and outcomes of kidney transplantation in a large European population. We found important differences with less favorable outcomes for black and Asian patients. Further research is required to address the barriers to optimal treatment among racial minority groups.

Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in mice

Deficiency of blood coagulation factor V or tissue factor causes the death of mouse embryos by 10.5 days of gestation, suggesting that part of the blood coagulation system is necessary for development. This function is proposed to require either generation of the serine protease thrombin and cell signaling through protease-activated receptors or an activity of tissue factor that is distinct from blood clotting. We find that murine deficiency of prothrombin clotting factor 2 (Cf2) was associated with the death of approximately 50% of Cf2−/− embryos by embryonic day 10.5 (E10.5), and surviving embryos had characteristic defects in yolk sac vasculature. Most of the remaining Cf2−/− embryos died by E15.5, but those surviving to E18.5 appeared normal. The rare Cf2−/− neonates died of hemorrhage on the first postnatal day. These studies suggest that a part of the blood coagulation system is adapted to perform a developmental function. Other mouse models show that the absence of platelets or of fibrinogen does not cause fetal wastage. Therefore, the role of thrombin in development may be independent of its effects on blood coagulation and instead may involve signal transduction on cells other than platelets.

Chemical camouflage of antigenic determinants: Stealth erythrocytes

In a number of clinical circumstances it would be desirable to artificially conceal cellular antigenic determinants to permit survival of heterologous donor cells. A case in point is the problem encountered in transfusions of patients with rare blood types or chronically transfused patients who become allosensitized to minor blood group determinants. We have tested the possibility that chemical modification of the red blood cell (RBC) membrane might serve to occlude antigenic determinants, thereby minimizing transfusion reactions. To this end, we have covalently bound methoxy(polyethylene glycol) (mPEG) to the surface of mammalian RBC via cyanuric chloride coupling. Human RBC treated with this technique lose ABO blood group reactivity as assessed by solution–phase antisera agglutination. In accord with this, we also find a profound decrease in anti-blood group antibody binding. Furthermore, whereas human monocytes avidly phagocytose untreated sheep RBC, mPEG-derivatized sheep RBC are ineffectively phagocytosed. Surprisingly, human and mouse RBC appear unaffected by this covalent modification of the cell membrane. Thus, mPEG-treated RBC are morphologically normal, have normal osmotic fragility, and mPEG-derivatized murine RBC have normal in vivo survival, even following repeated infusions. Finally, in preliminary experiments, mPEG-modified sheep RBC intraperitoneally transfused into mice show significantly improved (up to 360-fold) survival when compared with untreated sheep RBC. We speculate that similar chemical camouflage of intact cells may have significant clinical applications in both transfusion (e.g., allosensitization and autoimmune hemolytic disease) and transplantation (e.g., endothelial cells and pancreatic β cells) medicine.

Emergence of FY*Anull in a Plasmodium vivax-endemic region of Papua New Guinea

In Papua New Guinea (PNG), numerous blood group polymorphisms and hemoglobinopathies characterize the human population. Human genetic polymorphisms of this nature are common in malarious regions, and all four human malaria parasites are holoendemic below 1500 meters in PNG. At this elevation, a prominent condition characterizing Melanesians is α+-thalassemia. Interestingly, recent epidemiological surveys have demonstrated that α+-thalassemia is associated with increased susceptibility to uncomplicated malaria among young children. It is further proposed that α+-thalassemia may facilitate so-called “benign” Plasmodium vivax infection to act later in life as a “natural vaccine” against severe Plasmodium falciparum malaria. Here, in a P. vivax-endemic region of PNG where the resident Abelam-speaking population is characterized by a frequency of α+-thalassemia ≥0.98, we have discovered the mutation responsible for erythrocyte Duffy antigen-negativity (Fy[a−b−]) on the FY*A allele. In this study population there were 23 heterozygous and no homozygous individuals bearing this new allele (allele frequency, 23/1062 = 0.022). Flow cytometric analysis illustrated a 2-fold difference in erythroid-specific Fy-antigen expression between heterozygous (FY*A/FY*Anull) and homozygous (FY*A/FY*A) individuals, suggesting a gene-dosage effect. In further comparisons, we observed a higher prevalence of P. vivax infection in FY*A/FY*A (83/508 = 0.163) compared with FY*A/FY*Anull (2/23 = 0.087) individuals (odds ratio = 2.05, 95% confidence interval = 0.47–8.91). Emergence of FY*Anull in this population suggests that P. vivax is involved in selection of this erythroid polymorphism. This mutation would ultimately compromise α+-thalassemia/P. vivax-mediated protection against severe P. falciparum malaria.

Mapping regions containing binding residues within functional domains of Plasmodium vivax and Plasmodium knowlesi erythrocyte-binding proteins

Invasion of erythrocytes by malaria parasites is mediated by specific molecular interactions. Whereas Plasmodium vivax and Plasmodium knowlesi use the Duffy blood group antigen, Plasmodium falciparum uses sialic acid residues of glycophorin A as receptors to invade human erythrocytes. P. knowlesi uses the Duffy antigen as well as other receptors to invade rhesus erythrocytes by multiple pathways. Parasite ligands that bind these receptors belong to a family of erythrocyte-binding proteins (EBP). The EBP family includes the P. vivax and P. knowlesi Duffy-binding proteins, P. knowlesi β and γ proteins, which bind alternate receptors on rhesus erythrocytes, and P. falciparum erythrocyte-binding antigen (EBA-175), which binds sialic acid residues of human glycophorin A. Binding domains of each EBP lie in a conserved N-terminal cysteine-rich region, region II, which contains around 330 amino acids with 12 to 14 conserved cysteines. Regions containing binding residues have now been mapped within P. vivax and P. knowlesi β region II. Chimeric domains containing P. vivax region II sequences fused to P. knowlesi β region II sequences were expressed on the surface of COS cells and tested for binding to erythrocytes. Binding residues of P. vivax region II lie in a 170-aa stretch between cysteines 4 and 7, and binding residues of P. knowlesi β region II lie in a 53-aa stretch between cysteines 4 and 5. Mapping regions responsible for receptor recognition is an important step toward understanding the structural basis for the interaction of these parasite ligands with host receptors.

Toward optimized carbohydrate-based anticancer vaccines: Epitope clustering, carrier structure, and adjuvant all influence antibody responses to Lewisy conjugates in mice

The feasibility of using carbohydrate-based vaccines for the immunotherapy of cancer is being actively explored at the present time. Although a number of clinical trials have already been conducted with glycoconjugate vaccines, the optimal design and composition of the vaccines has yet to be determined. Among the candidate antigens being examined is Lewisy (Ley), a blood group-related antigen that is overexpressed on the majority of human carcinomas. Using Ley as a model for specificity, we have examined the role of epitope clustering, carrier structure, and adjuvant on the immunogenicity of Ley conjugates in mice. A glycolipopeptide containing a cluster of three contiguous Ley-serine epitopes and the Pam3Cys immunostimulating moiety was found to be superior to a similar construct containing only one Ley-serine epitope in eliciting antitumor cell antibodies. Because only IgM antibodies were produced by this vaccine, the effect on immunogenicity of coupling the glycopeptide to keyhole limpet hemocyanin was examined; although both IgM and IgG antibodies were formed, the antibodies reacted only with the immunizing structure. Reexamination of the clustered Ley-serine Pam3Cys conjugate with the adjuvant QS-21 resulted in the identification of both IgG and IgM antibodies reacting with tumor cells, thus demonstrating the feasibility of an entirely synthetic carbohydrate-based anticancer vaccine in an animal model.

Isolation of multiple sequences from the Plasmodium falciparum genome that encode conserved domains homologous to those in erythrocyte-binding proteins.

Open reading frames in the Plasmodium falciparum genome encode domains homologous to the adhesive domains of the P. falciparum EBA-175 erythrocyte-binding protein (eba-175 gene product) and those of the Plasmodium vivax and Plasmodium knowlesi Duffy antigen-binding proteins. These domains are referred to as Duffy binding-like (DBL), after the receptor that determines P. vivax invasion of Duffy blood group-positive human erythrocytes. Using oligonucleotide primers derived from short regions of conserved sequence, we have developed a reverse transcription-PCR method that amplifies sequences encoding the DBL domains of expressed genes. Products of these reverse transcription-PCR amplifications include sequences of single-copy genes (including eba-175) and variably transcribed genes that cross-hybridize to multiple regions of the genome. Restriction patterns of the multicopy genes show a high degree of polymorphism among different parasite lines, whereas single-copy genes are generally conserved. Characterization of the single-copy genes has identified a gene (ebl-1) that is related to eba-175 and is likely to be involved in erythrocyte invasion.

Nelson loose-leaf medicine /

Vol. 1. Infectious diseases. -- Vol. 2. Infectious diseases. Parasitic diseases. Chemical agents. Physical agents. -- Vol. 3. Metabolism. Endocrine glands. Lymph glands. Respiratory system. -- Vol. 4. Diseases of blood. Circulatory system. Kidney. -- Vol. 5. Diseases of digestive system. Muscles, bones, joints. -- Vol. 6. Diseases of nervous system. -- Vol. 7. Preventive medicine. -- Vol. 8. Research. Current literature.

Temperature dependence of the thrombin-catalyzed proteolysis of prothrombin

Measurement of the temperature-dependence of thrombin-catalyzed cleavage of the Arg(155)-Ser(156) and Arg(284)-Thr(285) peptide bonds in prothrombin and prothrombin-derived substrates has yielded Arrhenius parameters that are far too large for classical mechanistic interpretation in terms of a simple hydrolytic reaction. Such a difference from the kinetic behavior exhibited in trypsin- and chymotrypsin-catalyzed proteolysis of peptide bonds is attributed to contributions by enzyme exosite interactions as well as enzyme conformational equilibria to the magnitudes of the experimentally determined Arrhenius parameters. Although the pre-exponential factor and the energy of activation deduced from the temperature-dependence of rate constants for proteolysis by thrombin cannot be accorded the usual mechanistic significance, their evaluation serves a valuable role by highlighting the existence of contributions other than those emanating from simple peptide hydrolysis to the kinetics of proteolysis by thrombin and presumably other enzymes of the blood coagulation system. (C) 2004 Elsevier B.V. All rights reserved.

Parasitic infections and storage iron deficiency in children in improverished regions of Mauritius

Using a combination of techniques including relative deprivation index developed by the Government, school performance, household survey and drawing of lots, a sample frame constituting of poverty areas of Mauritius was constructed and four test areas identified. Relevant haematological, parasitological and biochemical parameters of all school-going children living in the four test areas were determined so as to study the possibility of correlation between parasitic infections, plasma ferritin, haemoglobin concentration, white blood cells count, packed cells volume and blood group. It was found that there is a negative correlation between the number of parasites and haemoglobin concentration, packed cells volume of blood and degree of infestation, number of parasites and ferritin and number of parasites and age of subject. It has also been found that, children with blood group 'A' and blood group '0' tend to harbour the most parasites. As regards to storage iron depletion, this is significant only with hookworm infestation. Additionally it has been noted that hookworm infestation is directly related to age contrary to other parasitic infestations.

A gold sol particle immunoassay for measurement of von willebrand factor using the CA-6000 analyzer

The diagnosis of Von Willebrand's disease (VWD) may sometimes be difficult because of the variability of the results obtained over time in individuals. Moreover, blood group, age, pregnancy and inflammatory stimuli influence the level of Von Willebrand Factor (VWF). The purpose of this thesis was to screen and characterize antibodies to Von Willebrand factor and to evaluate the most promising ones in a gold- Sol assay for VWF on the CA-6000 analyzer. Seven different lots of Anti-VWF antibodies, 3 polyclonal and 4 monoclonal Ab's were screened and evaluated. Two of these antibodies (Sunol R01358 and MAVWF-AP) were selected for preparation of a Gold coated antibody solution. The preliminary testing of these gold coated antibodies on CA-6000 Analyzer showed no immunoreactivity toward VWF for both individual and pooled plasma (from normal healthy donors). Although measurement of VWF for normal plasma with this technique was not demonstrated, these data will be valuable for future work on the design of sensitive and accurate automated sol Gold Immunoassays for the diagnosis of VWD.