bluuebunny/crossref_metadata_2025_split huggingface dataset:
The conundrum of neonatal coagulopathy
Authors: Revel-Vilk Shoshana 
Published: October 2019

Abstract
The maturation and postnatal development of the human coagulation system was first studied and described more than 20 years ago. These older studies, supported by more recent data, confirm the significant and important differences in the physiology of coagulation and fibrinolysis in neonates and young children compared with older children and adults. Subsequently, significant differences were also described in the physiology of primary hemostasis and in global in vitro tests for hemostasis. These differences, which mostly reflect the immaturity of the neonatal hemostasis system, are functionally balanced. Healthy neonates show no signs of easy bruising or other bleeding diathesis and no increased tendency to thrombosis for any given stimulus compared with adults. Systemic diseases may affect hemostasis, predisposing ill neonates to increased hemorrhagic or thrombotic complications. The immaturity of the hemostasis system in preterm and very-low-birth-weight neonates may contribute to a higher risk for intraventricular hemorrhage. Therapies targeting the hemostasis system can be effective for preventing and treating these events. The concept of “neonatal coagulopathy” has an important impact on both the diagnosis and management of hemorrhagic or thrombotic events in neonates. For diagnosis of hemostasis disorders, diagnostic laboratories processing pediatric samples should use age-, analyzer-, and reagent-appropriate reference ranges. Age-specific guidelines should be followed for the management of neonates with hemostatic disorders.
Myelodysplastic syndromes: who and when in the course of disease to transplant
Authors: Mufti Ghulam J. , Potter Victoria 
Published: October 2019

Abstract
The myelodysplastic syndromes are clonal hematopoietic disorders for which hematopoietic stem cell transplantation remains the only curative therapy. The timing of transplantation, methods of disease risk stratification, patient selection, pretransplantation therapies, and preparative regimens have evolved over the years, resulting in increasing disease-free survival. In recent years, alternative donor sources have been demonstrated to be a viable alternative to traditional sibling and matched unrelated donor stem cell sources. Efforts at transplantation regimen development continue with the aim of maximizing the chances of cure with minimal toxicity and improved quality of life. Integrating new knowledge regarding disease biology will be critical to continue to improve the success of hematopoietic stem cell transplantation. Exciting areas of ongoing research that may lead to reductions in posttransplantation relapse rate include posttransplantation therapies such as DNA methyltransferase inhibitors, vaccine strategies, and donor lymphocyte infusions to enhance the GVL effect.
Thrombotic disease in the myeloproliferative neoplasms
Authors: Falanga Anna , Marchetti Marina 
Published: October 2019

AbstractThrombosis is a leading cause of morbidity and mortality in patients with Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs), particularly polycythemia vera and essential thrombocythemia. Mechanisms involved in the pathogenesis of the acquired thrombophilic state associated with these diseases include abnormalities of MPN clone–derived blood cells, which display prothrombotic features, and abnormalities of normal vascular cells, which become procoagulant in response to inflammatory stimuli. Ultimately, the release into the blood of elevated levels of procoagulant microparticles by platelets and vascular cells and the increase in the global thrombin generation due to an acquired activated protein C resistance result in a highly prothrombotic scenario in patients with polycythemia vera and essential thrombocythemia. The acquired point mutation in the pseudokinase domain of JAK2 (JAK2V617F) in these disorders is variably associated with thrombosis and, more consistently, with elevations in WBC counts and alterations in biomarkers of blood-clotting abnormalities. The predictive value of these biomarkers for thrombosis remains to be established to identify subsets of patients at elevated risk who may benefit from prophylaxis with antithrombotic drugs.
Large granular lymphocytic leukemia: molecular pathogenesis, clinical manifestations, and treatment
Authors: Zhang Dan , Loughran Thomas P. 
Published: October 2019

Abstract
Large granular lymphocyte (LGL) leukemia represents a spectrum of rare lymphoproliferative diseases defined by clonal amplification of either CD3+ cytotoxic T-lymphocytes or CD3− natural killer cells. This chapter focuses on the T-cell form of LGL leukemia. Clinical features include neutropenia, anemia, and rheumatoid arthritis. LGL leukemia is thought to arise from chronic antigenic stimulation, with the long-term survival of LGL being promoted by constitutive activation of multiple survival signaling pathways, such as the JAK/STAT3, sphingolipid, and Ras/MEK/ERK pathways. Therefore, these lead to global deregulation of apoptosis and resistance to normal pathways of activation-induced cell death. The majority of LGL leukemia patients eventually need treatment. Treatment of leukemic LGL is based on immunosuppressive therapy, primarily using low doses of methotrexate or cyclophosphamide. However, no standard therapy has been established because of the lack of large, prospective trials. In addition, because some patients are refractory to currently available treatments and none of these therapeutic modalities can cure LGL leukemia, new therapeutic options are needed. Understanding the current state of the pathogenesis of LGL leukemia may provide insights into novel therapeutic options.
Plasma exchange: concepts, mechanisms, and an overview of the American Society for Apheresis guidelines
Authors: Winters Jeffrey L. 
Published: October 2019

AbstractPlasma exchange is a therapeutic procedure used to treat a variety of diseases through the bulk removal of plasma. To apply this treatment to patients appropriately, it is essential to understand the methods to remove plasma, its effects on normal plasma constituents, the role of replacement fluids in the treatment, and the risks associated with the procedure. To facilitate the appropriate evidence-based use of plasma exchange and to encourage research, the American Society for Apheresis has published guidelines providing practical guidance and information to those responsible for ordering or providing this treatment.
A look into the future: can minimal residual disease guide therapy and predict prognosis in chronic lymphocytic leukemia?
Authors: Ghia Paolo 
Published: October 2019

Abstract
Over the past 2 decades, dramatic improvements in the efficacy of treatments for chronic lymphocytic leukemia have led to progressively higher percentages of clinical complete remissions. A molecular eradication of the leukemia has become not only a desirable, but also an achievable, end point that needs to be evaluated within clinical trials. The assessment of complete remission only at the clinical and morphological level is insufficient, at least for physically fit patients. The detection of minimal residual disease (MRD) in chronic lymphocytic leukemia has become feasible using PCR-based or flow cytometric techniques that reproducibly allow reaching the detection level of less than 1 leukemic cell per 10 000 leukocytes (10−4), the level currently defined as MRD− status. Emerging data indicate that the MRD status during and at the end of treatment is one of the most powerful predictors of progression-free and overall survival. This predictor appears to be independent of clinical response, type or line of therapy, and known biological markers. For these reasons, the time is ripe to test the use of MRD as a surrogate marker of clinical end points and as a real-time marker of efficacy and/or resistance to the administered therapies. In the near future, clinical trials will determine whether MRD assessment can be used for guiding therapy, either to improve quality of responses through consolidation or to prevent relapses through preemptive therapies based on the reappearance of MRD.
Hodgkin lymphoma in children and adolescents: improving the therapeutic index
Authors: Kelly Kara M. 
Published: October 2019

AbstractHodgkin lymphoma (HL) is a highly curable form of childhood cancer, with estimated 5 year survival rates exceeding 98%. However, the establishment of a “standard of care” approach to its management is complicated by the recognition that long-term overall survival declines in part from delayed effects of therapy and that there continue to be subgroups of patients at risk for relapse for which prognostic criteria cannot adequately define. This challenge has resulted in the development of various strategies aimed at identifying the optimal balance between maintaining overall survival and avoidance of long-term morbidity of therapy, often representing strategies quite different from those used for adults with HL. More precise risk stratification and methods for assessing the chemosensitivity of HL through imaging studies and biomarkers are in evolution. Recent advances in the understanding of the biology of HL have led to the introduction of targeted therapies in both the frontline and relapsed settings. However, significant barriers exist in the development of new combination therapies, necessitating collaborative studies across pediatric HL research consortia and in conjunction with adult groups for the adolescent and young adult (AYA) population with HL.
Role of stem cell transplant and maintenance therapy in plasma cell disorders
Authors: McCarthy Philip L. , Holstein Sarah A. 
Published: October 2019

AbstractAutologous stem cell transplant (ASCT) has been an important component of therapy for myeloma patients eligible for high-dose chemotherapy. Recent studies comparing early transplant to low-dose chemotherapy support the continued use of ASCT as consolidation following induction therapy, even in the era of immunomodulatory drugs, proteasome inhibitors, and other novel agents. Despite the marked improvements in outcomes with this approach, most patients will eventually experience disease progression. Thus, inclusion of post-ASCT consolidation/maintenance strategies is used to improve long-term disease control. Multiple randomized studies support the use of lenalidomide maintenance therapy following ASCT. The next generation of clinical trials will incorporate novel agents such as monoclonal antibodies, proteasome inhibitors, and other novel pathway modulatory agents into post-ASCT treatment strategies with the goal of achieving even deeper responses and longer durations of disease control.
THE DIAGNOSIS OF HODGKIN'S DISEASE BY ASPIRATION BIOPSY
Authors: LOSEKE LUCILE , CRAVER LLOYD F. 
Published: October 2019

Abstract
1. Among 242 cases of histologically proved Hodgkin's disease treated at Memorial Hospital for the most part within the past five years, the diagnosis was established by open biopsy in 228, while in 14 cases aspiration biopsy yielded a reliable diagnosis.
2. In the 14 cases of Hodgkin's disease in which the diagnosis was made by examination of the sectioned clot obtained by aspiration biopsy, the material was from lymph nodes in 9 cases, from a presternal nodule in 1 case, from the lung in 3 cases, and from the spleen in 1 case.
3. Among the 228 cases in which formal biopsy was used to prove the diagnosis, aspiration biopsy had been previously attempted but had been unsuccessful in 11 cases.
Thus in 25 cases of the total number of 242, aspiration biopsy had been selected for good reason as the first method to try, and was diagnostically successful in 56 per cent of the group.
THE CARDIOVASCULAR SYSTEM IN ANEMIA
Authors: WINTROBE MAXWELL M. 
Published: October 2019

Abstract
The symptoms and signs referable to the cardiovascular system that are associated with anemia are discussed, and the physiologic adjustments to anemia that take place in the cardiovascular system are considered. The capacity for adjustment when anemia develops gradually, appears to be very great. The remarkable changes found in the cardiovascular system in cases of sickle cell anemia may be the result of adjustments to severe anemia of exceptional chronicity.
PLATELET COUNTS AND PLATELET FUNCTION
Authors: AGGELER PAUL M. , HOWARD JOAN , LUCIA S. P. , MILLS EDITH 
Published: October 2019

Abstract
Determinations of the platelet count, clot retraction, bleeding time, capillary fragility, and coagulation time were made in 64 normal subjects and in 404 patients suffering from various diseases.
The normal values for the platelet count done by an experienced technician using the Rees and Ecker method were: mean, 409,000 per cu. mm.; standard deviation, 68,000 per cu. mm.; normal range (M ± 2.σ), 273,000 per cu. mm. to 545,000 per cu. mm.
There was a statistically significant relationship between the platelet count and the results of tests of clot retraction, bleeding time, and capillary fragility, but there was no significant relationship between the platelet count and the coagulation time. Factors other than platelet count or platelet function which may influence the results of these tests are discussed.
The critical level of the platelet count, below which abnormal bleeding is likely to occur, was found to be approximately 190,000 per cu. mm. in primary thrombocytopenic purpura and 230,000 per cu. mm. in secondary thrombocytopenic purpura. However, platelet counts as low as 100,000 per cu. mm. were found in one patient without abnormal bleeding, and counts as high as 280,000 per cu. mm. were found in another patient with classical primary thrombocytopenic purpura.
In all patients in the active phase of bleeding in primary thrombocytopenic purpura and in most with secondary thrombocytopenic purpura, the bleeding time was markedly prolonged and clot retraction was definitely diminished. In approximately one half of the patients suffering from thrombocytopenia without bleeding or from thrombocytopenia complicating other hemorrhagic states, the results of these tests were abnormal. Capillary fragility was increased in approximately three fourths of the patients with primary thrombocytopenic purpura, one half with secondary thrombocytopenic purpura, and less than one half with thrombocytopenia without bleeding or with thrombocytopenia complicating other hemorrhagic states.
In the stage of recovery from thrombocytopenic purpura, dissociation of the results of the various tests was sometimes found. In some patients the platelet counts returned to normal hut abnormalities persisted in the tests of the bleeding time, clot retraction, or capillary fragility. In other patients the results of one or all of these tests returned to normal before the platelet count had reached the normal range. These results have been interpreted as evidence of variability in the functional capacity of the platelets.
SPECIFICITY OF ISOAGGLUTININ RESPONSE FOLLOWING INJECTION OF GROUP SUBSTANCES INTO GROUP O INDIVIDUALS
Authors: BOYD WILLIAM C. , LOWELL FRANCIS C. 
Published: October 2019

Abstract
The anti-A and anti-B titers in group O individuals may vary independently following injection of group-specific substances, although such independent variation was not always seen. The rise in anti-B which followed the injection of A sub stance in some instances may have been due to traces of B activity in the A substance or to nonspecific stimulation of antibody which may follow the injection of any antigen. The part played by such factors was not determined.
It is concluded that the presence of A and B agglutinins in O individuals is not dependent on a single cellular characteristic responsible for the simultaneous formation of the isoagglutinins.
Gene Interaction Resulting in Suppression of Blood Group Substance B
Authors: LEVINE PHILIP , ROBINSON ELIZABETH , CELANO MARINO , BRIGGS OLIVE , FALKINBURG LEROY 
Published: October 2019

Abstract
A family is presented in which the propositus and 2 siblings, apparently in group O, have in their sera anti-H in addition to anti-A and anti-B. Inspection of the family tree reveals apparent violations of Mendelian heredity which can be explained on the basis of a rare suppressor gene which in the homozygote state suppresses in the propositus the actions of gene B and secretion gene Se. The genes B and Se are fully expressed when transmitted to her offspring who are heterozygous for the suppression gene.
The same mechanism may be assumed to operate in the 9 other so-called group O bloods containing anti-H.
Observations on the Mechanism of Intranasal Absorption of Vitamin B12 in Pernicious Anemia
Authors: MONTO RAYMOND W. , REBUCK JOHN W. 
Published: October 2019

Abstract
Satisfactory clinical and hematologic response was obtained from the single application to the nasal mucosa of 200 and 150 micrograms of crystalline vitamin B12 in two patients with pernicious anemia.
Thirty-two patients with pernicious anemia in relapse and 55 in remission have been controlled satisfactorily by intranasal B12 either in saline solution, lactose powder, or as crystals. Absorption of the vitamin was probably direct and did not require binding with "intrinsic substance." Chronic disease of the nose did not contraindicate this modality of therapy; local irritation of the mucous membranes by the crystalline B12 or the vehicles employed has not been observed.
The Application of the Prussian Blue Stain to Previously Stained Films of Blood and Bone Marrow
Authors: SUNDBERG R. DOROTHY , BROMAN HARRIETTE 
Published: October 2019

Abstract
A simple method for staining non-hemoglobin iron in erythrocytes, normoblasts, macrophages, and other cells containing particulate iron in new or old films of cellular fluids or imprints of tissues and organs is presented. This method consists in using the prussian blue reagent as a type of counterstain; no separate decolorization is necessary. The preparations obtained resemble the original preparations except that iron stands out as a vivid blue-green material.
The method is particularly useful in studying conditions accompanied by varying degrees of iron excess or hemosiderosis of the marrow.
The stainable iron is all virtually the same color. The diffuse blue-green color of the cytoplasm of macrophages might be attributed to the more soluble form of iron, ferritin.
Stainable iron is visible in normoblasts and erythrocytes as well as in macrophages in sections subjected to the prussian blue reaction.
A prussian blue method using formalin fixation on fresh films of marrow7 has also been shown to be useful in the demonstration of particulate iron in previously stained films of marrow and blood. The formalin fixation appears to bring about a higher percentage of siderocytes.
Hemolytic Disease of the Newborn Due to Anti-A1
Authors: HUBINONT P. O. , LATIERS P. , MASSART-GUIOT T. 
Published: October 2019

Abstract
1. The authors report clinical, hematological and serological data in a case of A1 iso-sensitization of pregnancy.
2. The mother’s serum displayed immune characters specific to A1 cells immediately after delivery. On the 24th day post partum the specificity extended to A2 cells.
3. The disease exhibited by the infant was very mildly hemolytic. It was marked by a deep jaundice, repeated alimentary vomiting and a progressive state of drowsiness. There was no anemia. The direct anti-globulin test was negative.
4. It is shown that the mildness of the hemolytic process in cases of placental transfer of immune anti-A or anti-B into the incompatible A or B fetus is probably dependent upon a peculiar "resistance" of the fetal cells. This may be demonstrated in vivo and in vitro. In the present case replacement transfusion with A1adult blood resulted in its in vivo sensitization, detectable by the antiglobulin test and eventually leading to hemolytic anemia.
Multiple Myelomatosis Treated with a Combination of Urethane and an Oral Nitrogen Mustard
Authors: INNES JAMES , RIDER W. D. 
Published: October 2019

Abstract
1. 17 Cases of advanced multiple myelomatosis have been treated with combined chemotherapy using small doses of urethane and an oral preparation of nitrogen mustard.
2. The object of such therapy was to test the hypothesis that a synergistic action existed between these compounds.
3. The results indicate that significant palliation was obtained in many patients treated and that in some the progress of the disease was modified.
4. In the dosage employed such combined therapy appears to be free from undesirable toxic manifestations and suitable for out-patient administration over long periods.
Refractory Anemia Occurring in Survivors of the Atomic Bombing in Nagasaki, Japan
Authors: LANGE ROBERT D. , WRIGHT STANLEY W. , TOMONAGA MASANOBU , KURASAKI HIROTAMI , MATSUOKE SHIGERU , MATSUNAGA HARUJI 
Published: October 2019

Abstract
In this paper the case histories of six Nagasaki atomic bomb survivors who developed refractory anemia are presented. Four of these individuals received undoubted radiation injury. The fact that refractory anemia may occur as a late manifestation of exposure to atomic radiation is pointed out.
Clinical Manifestations of Inherited Abnormal Hemoglobins
Authors: STURGEON PHILLIP , ITANO HARVEY A. , BERGREN WILLIAM R. 
Published: October 2019

Abstract
A clinical and hematologic description is presented of the family demonstrating the existence of the genetically determined hemoglobin-D originally described by Itano.
The interaction of hemoglobin-D with hemoglobin-S in two members of this family has resulted in a hemolytic process and a mild anemia. Clinically, one of the patients is asymptomatic. The other has repeated painful episodes characteristic of those seen in sickle cell crises.
Clinical and hematologic evaluations of two members of the family inheriting normal hemoglobin and hemoglobin-D revealed no abnormalities.
The only feature of hemoglobin-D which distinguishes it from normal hemoglobin is its electrophoretic mobility which is similar to that of hemoglobin-S. Hemoglobin-D is distinguished from hemoglobin-S by a higher solubility and by a failure to sickle and from hemoglobin-C by a lack of target cell formation and a different electrophoretic mobility.
Clinical, hematologic and special hemoglobin studies are presented of a family exhibiting a new abnormal hemoglobin (hemoglobin-E). Its interaction with thalassemia trait in one of its members also is described.
Hemoglobin-E does not sickle; under alkaline conditions it migrates slowly at a rate comparable to hemoglobin-C, while at an acid pH it migrates at a rate similar to hemoglobin-S.
The result of its interaction with thalassemia is a microcytic, hypochromic anemia clinically resembling thalassemia major of an intermediate degree of severity. The major defect appears to be in hemoglobin synthesis, although the slight persistent reticulocytosis suggests a mild hemolytic process.
Comparative Incorporation of S35 L-Cystine and S35 Sodium Sulfate by Normal and Leukemic Leukocytes
Authors: WEISBERGER AUSTIN S. , SUHRLAND LEIF G. 
Published: October 2019

Abstract
1. Certain differences are demonstrated in the metabolic turnover of l-cystine sulfur and inorganic sulfur by normal and leukemic leukocytes. These differences are apparent both in vivo and in vitro and may be associated with factors peculiar to the metabolism of leukemic leukocytes.
2. The incorporation of S35 l-cystine or S35 sodium sulfate by leukocytes appears to be associated primarily with the presence of immature granulocytes.
3. Both l-cystine (or l-cysteine) and sulfate may be of importance in the metabolism of leukocytes.