bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Rebleeds in Cost Modelling of Treatment Strategies in Patients with Hemophilia A and Inhibitors.
Authors: Huth-Kuehne Angela , Lages Peter , Zimmermann Rainer 
Published: October 2019

Abstract
Introduction: To investigate the cost-effectinvess of the treatment in patients with hemophilia and inhibitor, the expected number of rebleeds in home treatment is an important factor if one compares different treatment options e.g. APCC or rFVIIa. To evaluate the economic impact in mild to moderate bleeds in home treatment we used a robust established model to compare 1st, 2nd and 3rdline treatment either with rFVIIa or APCC. For the rate of rebleeds we refer to published data on a broad basis.
Methods: To compare the economic impact of different treatment regimes, this model refers to an on-demand home treatment of bleeding episodes in adult hemophiliacs (mean body weight 75 kg) and is based on a previously published flow-diagram and calculation formula (Knight 2003). Dosage per bolus: rFVIIa 90μg/kg, aPCC 60 U/kg. Costs for German market were fixed at 1.21 €/IU for APCC, 0.73 €/μg for rFVIIa and 308.98 €/day in hospital. 3 treatment strategies (TS) were calculated:
TS 1:
APCC at home, followed by in hospital APCC (2nd-line) and rFVIIa (3rd-line)
TS 2:
APCC at home, followed by in hospital rFVIIa (2nd-line) and rFVIIa (3rd-line)
TS 3:
rFVIIa at home, followed by in hospital rFVIIa (2nd-line) and rFVIIa (3rd-line)
The model was based on published data on dosing and outcome of therapy in each treatment phase. Probability of failure to control bleeding or rebleeding after first-line home treatment was set at 23.5% with APCC and 9.1% with rFVIIa.
Results: Median costs for TS 1 are 23,521 Euro per bleeding episode as compared to 21,963 Euro for TS 2 and 14,328 Euro for TS 3. The difference is caused by costs for first attempt to control bleeding at home (APCC 16,335 Euro as compared to rFVIIa 11,333 Euro) and costs at later stages of treatment. Further analyses show, that favorable result for TS 3 is robust to changes of different parameters such as patients’ weight.
Conclusions: First line treatment with rFVIIa in case of on demand treatment seems to be the most cost effective option in inhibitor treatment in a home treatment setting or in-hospital treatment. Local prices have to be taken into consideration.
Prognostic Value of Non-Overt DIC Criteria in Patients with Sepsis.
Authors: Jang Moon Ju , Chong So Young , Kang Myung Seo , Lee Sun Ju , Oh Doyeun 
Published: October 2019

Abstract
DIC is a frequent complication of sepsis resulted in high mortality. The early diagnosis of DIC in septic patients is necessary to reduce the mortality by the prevention of irreversible organ damage through earlier therapeutic intervention. We investigated the performance of the ISTH non-overt DIC criteria and its modification by adding antithrombin (AT), protein C and Organ Failure Scoring (OFS) system for mortality prediction were evaluated in 100 septic patients prospectively enrolled between July 2004 and March 2006. Platelet count, PT, aPTT, fibrinogen, D-dimer, AT, protein C on day 0,1,2,3,4, and 7 were measured in each patient. ISTH overt and non-overt DIC scoring with 28-day mortality, OFS was evaluated to assess the diagnostic value of each criterion in the prediction of clinical outcome. Twenty-five, 14 and 61 had overt DIC, non-overt DIC and non-DIC respectively. Platelet count, PT, AT, protein C levels were significantly different between DIC and non-DIC. D-dimer and protein C levels were significantly different between overt and non-overt DIC. The 28-day mortality rate of overt DIC, non-overt DIC and non-DIC was 44, 50 and 11.5% respectively. By adding AT and protein C on non-overt DIC criteria, the 28-day mortality rate of overt DIC, non-overt DIC and non-DIC became changed to 44, 31.4 and 7.5% respectively, but there was no difference between overt and non-overt DIC patients. Addition of AT, protein C or OFS to ISTH non-overt DIC criteria did not improve the diagnostic power significantly. In conclusion, ISTH non-overt DIC criteria is feasible to predict the poor outcome of septic patients.
Platelet and Coagulation Activation in Myeloproliferative Diseases (MPD), and Relationship to JAK2(V617F) Mutation Status and Clonality.
Authors: Robertson Beverley J. , Urquhart Colin , Ford Isobel , Watson Henry G. , Vickers Mark , Greaves Michael 
Published: October 2019

Abstract
Patients with MPD have an increased risk of thrombosis. Previous reports suggest an association between clonality and thrombosis in ET. The contribution of the JAK2 mutation to thrombotic risk is unclear. In our cohort of patients with MPD (n=122) (PRV n = 54, ET n = 64, IMF n= 4), we compared coagulation and platelet activation markers (D-Dimers, thrombin antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2), soluble E-selectin(sE-selectin) and soluble P-selectin(sP-selectin)) between MPD patients and hypertensive controls. sP-selectin was significantly increased in patients with MPD (p=<0.001). The JAK2 mutation status was determined in our cohort by ARMS PCR. Of the total MPD cohort, 59% were JAK2 positive, (76% of PRV, 45% of ET, and 50% of IMF). Coagulation activation markers were compared in JAK2 positive and JAK2 negative patients. sP-selectin levels were highly significantly elevated in JAK2 positive patients compared to JAK2 negative (p= 0.002), or controls (p<0.001).
There was no significant difference in platelet count between JAK2 positive and negative patients (p=0.19). The clonality of the MPD was determined in 54 female patients using an x-chromosome inactivation pattern (XCIP) assay (HUMARA). A significant proportion of “polyclonal” patients, as defined by XCIPs were positive for the JAK2 mutation. We therefore calculated the proportion clonality of samples and found no correlation between proportion clonality and any coagulation or platelet activation marker.
Our results show an increase in platelet activation, as determined by sP-selectin levels, in patients with MPD compared to controls. Furthermore, platelet activation was a feature of patients positive for the JAK2 mutation when compared with wild type patients and controls. The role of the JAK2 mutation as a risk factor for thrombosis in MPD is still unclear but our study indicates that the presence of the mutation may be linked to platelet activation in MPD. Whether this translates into a higher clinical thrombosis risk requires further evaluation in a large prospective study.
Human Cell Expressed Cytokines for Expansion of CD34+ Hematpoietic Stem Cells.
Authors: Rede Teresa , Domagala Teresa , Liddell Kate , Crofts Linda , Pilkington Glenn , Marks Denese 
Published: October 2019

Abstract
Many cytokines and growth factors are heavily glycosylated, with up to 75% of their mass consisting of carbohydrate moieties. Glycosylation is important for secretion, solubility, resistance to proteolysis, immunogenicity, biological recognition, biological activity, in vivo stability and clearance of glycoproteins including cytokines and growth factors. This study was designed to compare the ability of human cell expressed cytokines to induce CD34+ hematopoietic stem cell expansion with human cytokines expressed in E. coli. CD34+ stem cells were cultured with either human cell expressed G-CSF and stem cell factor (SCF), or with human G-CSF and SCF expressed in E. coli. CD34+ stem cell expansion was determined by counting total nucleated cells (TNC), and colony forming unit (CFU) potential of the expanded cells was determined by colony number, size and cell morphology. During early cell proliferation and expansion, the TNC count of cells treated with the human cell expressed cytokines was markedly higher than cells treated with E. coli expressed human cytokines. In CFU assays, the size and mean number of colonies were greater with the human expressed G-CSF and SCF cytokine combination. In addition, the proportion of colonies with macrophage-like morphology was greater. Human cell expressed cytokines also induced greater myeloid differentiation as indicated by higher CD33 expression compared to cytokines expressed in E. coli.
We are currently investigating the ability of human cell expressed G-CSF/SCF to activate signaling pathways including the MEK/ERK and STAT pathways, which are known to be involved in G-CSF mediated proliferation and differentiation. Differences in receptor-ligand binding using ligands from various expression systems are also being examined.
The ability of human cell expressed cytokines to induce greater in vitro differentiation and proliferation of hematopoietic stem cells may translate to better ex vivo expansion protocols.
A High-Density MicroRNA Array for Analyzing the Expression of 15,090 Verified and Predicted Small, Non-Coding RNAs.
Authors: Wilson Michael , Leng Nan , Sah Sachin , Sekinger Edward , Fletcher Frederick , Johnson Charles 
Published: October 2019

Abstract
We have designed and evaluated the performance of a custom Affymetrix microRNA (miRNA) microarray that enables the analysis of 15,090 unique mature miRNAs that are predicted or biologically verified. The comprehensive probe content of the array was selected from multiple sources including the Sanger miRBase sequence database (version 8.0), published reports, and a proprietary database of predicted miRNAs. Most of the ~31,000 25-mer probes on the array were designed by selecting two overlapping oligonucleotide sequences that span the mature miRNA sequences and a portion of the flanking precursors (pre-miRs). We also included antisense control probes as well as probes that target the predicted hairpin loop region of the pre-miR for a subset of well-characterized human miRNAs. We evaluated the array performance using a model system of two total RNA reference standards isolated from different tissues that were mixed in calibrated ratios. The custom array performance was compared to an enhanced mirVana™ miRNA Bioarray, using the same calibrated mixtures of reference RNAs. We assessed the reproducibility, relative sensitivity, dynamic range and concordance between the results from the two platforms. The performance of the two platforms was similar, with both platforms reliably detecting differential miRNA expression. For those miRNAs that are represented on both platforms, there was a strong correlation of the log2 ratios of differential expression levels between the RNA reference standards. Many of the miRNAs with detectable expression signals were novel predicted miRNAs derived from bioinformatic exploration of human genomic sequence data. This provides initial evidence that some of the predicted miRNAs are expressed in tissues and, therefore, may function as regulators by mechanisms consistent with other well-characterized miRNAs. In summary, our data illustrate the technological and biological feasibility of the custom high-density miRNA microarray for the comprehensive identification and global expression profiling of novel miRNAs.
Osmotic Fragility of Human Blood Platelets
Authors: GUREVITCH J. , NELKEN D. 
Published: October 2019

Abstract
The osmotic fragility of 50 samples of platelets from normal healthy donors has been studied. It has been found that fragility of platelets starts at a concentration of about 0.44 per cent NaCl and is complete at a concentration of 0.34 per cent. The serotonine released from the platelets increased with the gradual disintegration as the saline concentration fell.
Ultrastructure of Erythrocyte Membranes in Thalassemia Major and Minor
Authors: HOFFMAN J. F. , WOLMAN I. J. , HILLIER J. , PARPART A. K. 
Published: October 2019

Abstract
The plasma membranes of erythrocytes derived from Thalassemia major (five cases) and minor (seven cases) were isolated and studied by electron microscopy. It was found that the surface texture of ghosts from all T. minor bloods appeared similar and indistinguishable from ghosts of normal humans blood. The surface texture of ghosts from all T. major bloods likewise were quite similar but distinctly different from T. minor and normal ghosts. These differences were observable whether the specimens for comparison were prepared at the same time or on different days. The results indicate that the morphological characteristics observed in T. major ghosts constitute an expression of an alteration in the molecular structure of their plasma membranes.
Sickle Cell Anemia (Homozygous S) with Aseptic Necrosis of Femoral Head
Authors: TANAKA KOUICHI R. , CLIFFORD GEORGE O. , AXELROD ARNOLD R. 
Published: October 2019

Abstract
1. Six patients with sickle cell anemia who exhibit aseptic necrosis of the femoral head are presented.
2. All patients were proven homozygous S by paper electrophoresis.
3. In our material, aseptic necrosis of the femoral capital epiphysis in patients with sickle cell anemia is not an uncommon finding, 12% of 51 cases demonstrating this lesion.
4. The incidence of this lesion may be even greater than we report, inasmuch as some of our patients were asymptomatic, although typical roentgenographic changes of aseptic necrosis of the femoral head were present.
The Hemostatic Defect of Uremia
Authors: LARRAIN CAMILO , LANGDELL ROBERT D. 
Published: October 2019

Abstract
Acute urinary retention was produced in 15 adult mongrel dogs by ligation of the ureters. Studies of the hemostatic mechanism were made as the uremia progressed. All animals developed a coagulation defect characterized by abnormally long clotting time of whole blood in siliconized glassware. Other indices of coagulation efficiency were found to be normal or only slightly impaired.
It is not clear whether the basic defect is a lack of an essential clotting factor or an excess of an inhibitor. Urea does not seem to be the cause of the defect. The data suggest that the duration of urinary retention is as important as the degree of azotemia.
Immunologic Features of Erythrocyte Sensitization
Authors: VAUGHAN JOHN H. 
Published: October 2019

Abstract
By the use of specifically absorbed Coombs sera, it has been possible to show that cell sensitization in acquired hemolytic disease may be due either to γ-globulin or to non-γ-globulin serum components. The latter may be either warm reacting or cold reacting (cold agglutinin).
In certain instances acquired hemolytic disease is associated with autoimmunization. In other instances, it is possible that nonspecific adsorptive processes are involved, though definitive evidence for this is lacking.
The "Morular Cell" and the "Grape Cell" in Bone Marrow and Peripheral Blood
Authors: ZLOTNICK AVINOAM 
Published: October 2019

Abstract
Bone marrow aspirates of 39 patients with different diseases were examined. In 8 of these patients, who showed hyperglobulinemia of nonmyelomatous origin, three kinds of cells were found:
1) Plasmocytoid reticulum cells whose cytoplasm was filled with crystal-like configurations.
2) Plasmocytoid reticulum cells with hyaline transparent vesicles of different sizes in the cytoplasm. These cells resembled the "morular cell" of Mott.
3) Plasma cells the cytoplasm of which contained opaque bluish staining globular bodies varying in number and size. These cells were identical with the "grape cell."
The "grape cell" was also found in the buffy coat of the blood from 2 patients with hyperglobulinemia, and the "morular cell" in the buffy coat from a patient suffering from an unusual parasitic disease.
The protein nature of these inclusions is assumed, since they stained with the M.G.G. combination, but did not stain with Sudan black nor with P.A.S.
The Response of Transplanted Chloroleukemia in the Rat to Treatment with Antileukemic Drugs
Authors: SHAY HARRY , HARRIS CHARLES , GRUENSTEIN MARGOT 
Published: October 2019

Abstract
Using a short-term screening program, we have demonstrated a parallelism in response between our myelogenous chloroleukemia in the rat and that of myelogenous leukemia in man when treated with a number of chemotherapeutic agents.
Erythrokinetics: Quantitative Measurements of Red Cell Production and Destruction in Normal Subjects and Patients with Anemia
Authors: GIBLETT ELOISE R. , COLEMAN DANIEL H. , PIRZIO-BIROLI GIACOMO , DONOHUE DENNIS M. , MOTULSKY ARNO G. , FINCH CLEMENT A. 
Published: October 2019

Abstract
Red cell turnover of 19 normal subjects and 25 anemic patients was measured with the following technique: erythroid-myeloid ratio of the marrow, reticulocyte counts, plasma iron turnover, red cell utilization of radioiron, and urobilinogen determinations. Measurements of blood production and destruction were so expressed as to allow comparison between normal and anemic individuals of different size and different red cell mass. The usefulness and disadvantages of each procedure in the study of anemia are discussed.
From studies of various types of anemia, it has become apparent that erythropoiesis must be defined in terms of total quantity of red cells produced and in terms of the portion of red cells produced in the marrow which are delivered to the circulating blood (effective versus ineffective erythropoiesis). A quantitative defect alone exists when a normal ratio is maintained between effective and total erythropoiesis. Here, there are changes of similar magnitude of all erythrokinetic indices, although reticulocyte and urobilinogen values are occasionally disproportionately high. The normal marrow appears to be able to increase its effective red cell production to three times normal in acute anemia and six times normal in chronic anemia. In many disease states this maximal quantitative response is impaired.
Dyspoiesis of the marrow is characterized by a dissociation of erythrokinetic indices. Values which reflect total erythropoiesis (i.e., plasma iron turnover, fecal urobilinogen and erythroid-myeloid ratio of the marrow) are considerably greater than the reticulocyte level and red cell utilization of radioiron which represent effective erythropoiesis. Such defects may result in the pattern of a hemolytic process or aregenerative anemia, depending on their severity.
The Plasma Erythropoietic Stimulating Factor
Authors: LINMAN AMES W. , BETHELL FRANK H. , TASCOTT HELENA K. 
Published: October 2019

Abstract
1. Boiled plasma extracts from anemic rabbits are capable of stimulating erythropoiesis in normal rats as demonstrated by reticulocytosis, erythrocytosis, and increased marrow erythropoietic activity.
2. In the nonanemic rat recipient the increased erythropoiesis is manifested by the production of cells of decreased size without associated increase in the hemoglobin or hematocrit determinations. The cells probably have a greatly shortened life span.
3. The factor in anemic rabbit plasma is not destroyed by prolonged boiling and is not precipitated by perchloric acid. On the basis of these observations it would seem to be nonprotein in nature.
4. Further investigations concerning the role of the erythrocyte stimulating factor in normal and abnormal erythropoiesis should be facilitated by the use of nonprotein plasma extracts which may be administered to small laboratory animals.
Study of Leukocyte Dynamics by Means of Cross-Circulation Between Normal and Leukopenic Rats
Authors: HOLLINGSWORTH J. W. , FINCH STUART C. , CHANG CHU H. , CHALTAS MARY 
Published: October 2019

Abstract
(1) Certain aspects of leukocyte dynamics in rats were studied by means of a mechanical cross-circulation technic.
(2) Cross-circulation between two normal rats caused little change in the leukocyte counts.
(3) When irradiated leukopenic animals were cross-circulated with normals, the leukocyte counts of the normal animals were moderately decreased, while the level of the irradiated animals rose. Prolonged mixing of the circulations, however, failed to bring the counts of the two animals into equilibrium.
(4) After cessation of cross-circulation, the leukocyte counts of the normal donors usually rose slowly, while those of the irradiated animals fell progressively with a half-time disappearance of 30-60 minutes.
(5) The possible significance of these observations in terms of normal leukocyte mobilization, viability and destruction was discussed.
Granulomatous Lesions in Bone Marrow
Authors: PEASE GERTRUDE L. 
Published: October 2019

Abstract
A survey has been made of granulomatous lesions found in sections of bone marrow from 150 patients studied at the Mayo Clinic. These lesions have been found in a variety of disorders, some with known etiologic agents and others with unknown causes.
With the exception of tuberculosis, histoplasmosis and brucellosis, in which the causative organisms were seen and identified bacteriologically, the granulomatous lesions were not thought to have any distinctive histopathologic characteristics.
Prominent lesions, Langhans’ giant cells and necrosis were more common in the marrow of patients with disorders known to be associated with a granulomatous inflammatory process than they were in associations with other conditions.
Specificity of Lytic Factors for Erythrocytes, Leukocytes and Platelets in a Case of Pancytopenia
Authors: MATOTH Y. , ELIAN E. , NELKEN D. , NEVO A. C. 
Published: October 2019

Abstract
A case of chronic idiopathic pancytopenia in a young girl is presented, in which the pancytopenia was shown to be due to increased destructions of all 3 blood cell types. Antileukocyte and antiplatelet antibodies were demonstrated by transfusion methods as well as by in vitro agglutination, while differential agglutination provided evidence of a plasma factor causing increased red cell destruction.
Cross absorption experiments demonstrated the presence in the patient’s serum of at least 2 separate and distinct antibodies, specific for leukocytes and platelets respectively.
Observations on the phagocytic behavior of leukocytes and on the electrophoretic mobility of leukocytes and platelets exposed to the patient’s serum are reported.
Paroxysmal Nocturnal Hemoglobinuria
Authors: NUSSEY A. M. , DAWSON D. W. 
Published: October 2019

Abstract
1. A fatal case of P.N.H. in a woman of 65 is presented.
2. The subject of P.N.H. is briefly discussed, and
3. The involvement of the bone marrow in the disease process is stressed.
Hemorrhagic Disease with Circulating Inhibitors of Blood Clotting: Anti-AHF and Anti-PTC in Eight Cases
Authors: LEWIS JESSICA H. , FERGUSON JOHN H. , ARENDS TULIO 
Published: October 2019

Abstract
In eight patients suffering from severe hemorrhagic disease it was possible to demonstrate the presence of circulating inhibitors, not heparin-like in nature. Anti-PTC was identified in two PTC deficients, anti-AHF in 5 hemophilics and both, primarily anti-AHF, in one idiopathic case. Possible etiologic factors inducing the appearance of such inhibitors included repeated transfusions of whole blood and plasma in all and a previous pregnancy in the idiopathic case. Two patients showed increases of gamma-globulin and presence of inhibitor in 25-33 per cent ammonium sulfate plasma fractions. Cortisone therapy was ineffective in two cases.