bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Community Cancer Center Experience of the Efficacy and Safety of the Use of Intravenous Iron Dextran in Chemotherapy Induced Anemia.
Authors: Sen Kaushik , Okoro Ngozi O. , Hedman Theresa R. 
Published: October 2019

Abstract
An adequate level of hemoglobin is essential during chemotherapy in order to maintain an acceptable quality of life (QOL) and to prevent cancer related fatigue. The role of hematopoitic growth factors like Erythropoitin or Darbepoitin alfa in chemotherapy induced anemia is now well-accepted with the recommended goal being a hematocrit value of 33% approximately. It is also established that an iron-replete state is essential for proper response to the erythropoitic growth factors and IV iron supplementation has been in routine clinical use in long term hemodialysis patients. Unfortunately many cancer patients are nutritionally depleted and at the same time do not tolerate oral iron replacement. Intravenous iron preparations such as iron dextran or sodium ferric gluconate (Ferrlecit) are good alternatives because of their quick and predictable effect on erythropoisis. However due to heightened concern about infusion related serious side effects their use has not been widespread in community clinical practice. We present our experience of treating 30 patients (7 lung cancer, 6 breast cancer, 3 lymphoma, 6 colorectal, 4 ovarian, 4 others) in our center with documented chemotherapy induced anemia with supplemental intravenous iron. None of the patients had any history of untreated pretreatment iron deficiency anemia. Utilizing a premedication protocol of hydrocortisone 100mg, benadryl 25 mg and ranitidine 50 mg IV prior to iron infusion we could record only 2 cases with grade I/II (mainly nausea and dizziness) and none with grade III/IV acute infusion related toxicity. Only one patient required treatment interruption and no one required hospitalization due to adverse events. There was no death associated with this therapy. The pretreatment average hematocrit was 29.26% (range 26.4–32.3%). The average posttreatment hematocrit was 35.33% (range 33.1–44.6%) within an average of 4 weeks. All patients were treated with Erythropoitin (40,000 unit/wk) or Darbepoitin alfa (200 mg/14 days) during the period of observation. All patients received their respective chemotherapy for the primary cancer without interruption. The effect persisted over the next 10–14 weeks during which the primary therapy was continued. No long term adverse effect was observed during this period of observation.
Conclusion- This small observational study indicates that intravenous iron infusion is a safe procedure in the community cancer center setting. It has the potential of significantly augmenting the effect of erythropoitic growth factor therapy for chemotherapy induced anemia. Further studies are required to evaluate the routine use of intravenous iron in chemotherapy induced anemia similar to its use with erythropoitin in patients on chronic hemodialysis.
Cocaine’s Direct Effect on Either Sickle or Normal Erythrocytes Does Not Increase Phosphatidylserine Exposure, Calcium Pumping, or Scramblase Activity.
Authors: DeJong Kitty , Hagar Robert 
Published: October 2019

Hypothesis: Cocaine directly affects the exposure of phosphatidylserine, calcium pumping, and scramblase activity in sickle cells.
Background: Cocaine is highly associated with pulmonary hypertension in both normal and sickle cell disease patients. Given the growing interest in pulmonary hypertension as a major morbidity factor, the causes and determinants of pulmonary hypertension need to be elucidated to allow rational study designs. Phosphatidylserine (PS) exposure is known to occur in sickle cells and appears to be relevant for vascular damage. Although the mechanism underlying PS exposure is poorly understood, signal transduction processes appear to play a role. We wondered if cocaine could activate these processes and cause PS exposure, or interfere with the proteins involved in the transbilayer movement of PS.
Methods: Sickle and normal erythrocytes were exposed to cocaine HCl (from a 10% topical solution, Roxane Labs) at concentrations between 100 and 1000 ng/ml, which is the range of determined plasma concentrations after cocaine use. PS exposure after cocaine treatment was measured by labeling with fluorescently conjugated annexin V (AV) and analysis by flow cytometry. Alterations in scramblase activity were determined by assessing the percentage of PS-exposing cells following loading of the cells with 0.1 mM calcium using calcium ionophore. Calcium influx and Ca-ATPase-mediated calcium efflux were monitored using the fluorescent probe Fluo4, and flippase activity was assessed using NBD-PS followed by analysis with flow cytometry.
Results: Sickle cells differ from normal cells with respect to most of the measured parameters, such as having more PS-exposing cells, lower flippase activity, and alterations in calcium kinetics. However, cocaine did not have any effect on PS exposure, calcium-induced scrambling, calcium influx, calcium pump activity, or flippase activity. The cell scatter patterns did not show any gross changes in red cell shape or density after cocaine treatment.
Discussion: The lack of effect implies that cocaine is working through other mechanisms than effects on red cell membranes. Therefore, future studies should focus on other vascular cell types and membrane pathways. Alternatively, cocaine metabolites should be evaluated for their activities on red cells.
Impact of Early Factor VIII Exposure, Prophylaxis and Prenatal/Perinatal Events on Inhibitor Risk in Children with Hemophilia A: A Case-Control Study.
Authors: Santagostino Elena , Rocino Angiola , Mancuso Maria E. , Mazzucconi Maria G. , Mancuso Giacomo , Messina Maria , Tagliaferri Annarita , Luciani Matteo , Boeri Elio , Mannucci Pier M. 
Published: October 2019

Abstract
In a multicenter case-control study we investigated the impact of prenatal/perinatal events and early FVIII exposure on the inhibitor risk in hemophiliacs. Patients: 102 children (age:13–196 months) with hemophilia A (FVIII≤2%) exclusively treated with recombinant FVIII and evaluated for inhibitors every 3 months were included. Forty-seven patients who developed inhibitors at the median age of 26 months (4–80) after a median of 16 exposure days (ED, 5–150), 37 high-responders (6–500 BU/mL) and 10 low-responders (<5 BU/mL), were compared with 55 children who did not develop inhibitors after at least 20 ED (5<50, 4<100, 10<200 and 36>200 ED). Results: by univariate analysis, family history of inhibitors, intron 22 inversion and prophylaxis started after the first 20 ED were significantly associated with an increased risk of inhibitor development (OR 9.5, 95%CI 1.1–79.9; OR 2.7, 95%CI 1.1–6.6; OR 3.7, 95%CI 1.1–12.1, respectively). No statistically significant differences were found for variables such as villocentesis/amniocentesis, premature/caesarian birth, breast-feeding, surgery, central venous devices and FVIII infusions associated with infections/vaccinations. By multivariate analysis, the inhibitor risk was 2.8-folds (95%CI 1.1–7.3) in children with intron 22 inversion and 4.5-folds (95%CI 1.1–17.5) in patients who started prophylaxis after the first 20 ED. By univariate and multivariate analysis, there was not a linear trend in the inhibitor development according to the age at first FVIII exposure (≤6, 7–12, 13–18, 19–24, >24 months). Conclusions: this study showed that starting prophylaxis within the first 20 ED had a favourable impact on the inhibitor risk independently from the age at first FVIII exposure.
Pulmonary Hypertension in Pediatric Patients with Sickle Cell Disease; a Retrospective Study.
Authors: Young Eric M. , Zilberman Mark V. , Du Wei , Sarnaik Sharada A. 
Published: October 2019

Abstract
Background: While pulmonary hypertension (PHT) contributes significantly to the morbidity and mortality of adults with sickle cell disease (SCD), it has not been studied in pediatric SCD patients. We sought to evaluate the prevalence and significance of PHT in pediatric SCD population.
Methods: From May 1999 to July 2004, 123 echocardiograms were performed in SCD patients. Utilizing the tricuspid valve regurgitant jet, right ventricular systolic pressure (RVSP) was estimated in 56 studies (47 patients, aged 0 to 18 years). PHT was defined as RVSP >30 mmHg.
Mean steady-state as well as the most recent white blood count (WBC), hemoglobin (Hb) level, reticulocyte count, ferritin level, and number of red cell units transfused in the year prior to the study were noted. In addition, all chest X-ray readings were reviewed to determine the number and type of life-time pulmonary events (effusions, infiltrates, pneumonia, atelectasis or CHF) in each patient. Acute chest syndrome (ACS) was determined to be any effusion, infiltrate or pneumonia.
Statistical analysis included Fisher’s exact test and Spearman’s correlation coefficients.
Results: Eleven patients were acutely ill at the time of the echocardiogram and were excluded from the analysis. Of the remaining 36 patients, pulmonary hypertension was present in 24 (66%). There was a significant difference in RVSP between younger (0 to 9 years) and older (10 to 18 years) groups of patient (p<0.004). There was a positive correlation between the age and RVSP (r = 0.36; p = 0.031).
A significant negative correlation was shown between RVSP and most recent Hb (r = −0.41; p = 0.012) as well as RVSP and the mean steady state platelet count (r = −0.35; p = 0.035). A positive correlation was found between RVSP and the number of ACS episodes (r = 0.37; p = 0.024), RVSP and mean steady state reticulocyte count (r = 0.51; p = 0.002) as well as the most recent reticulocyte count (r = 0.42; p = 0.012). There was however, no correlation found between RVSP and the number of episodes of CHF, collapse or atelectasis separately or grouped together. No correlation was found between RVSP and the number of units transfused or ferritin level.
Conclusion: Pulmonary Hypertension is highly prevalent in the pediatric SCD population and its prevalence increases with age. It correlates with indicators of acute and chronic hemolysis as well as the number of ACS events. Our study did not demonstrate correlations between PHT and iron overload indices. Prospective clinical trials monitoring PHT in SCD pediatric patients are indicated.
In Vitro Modulation of Cellular Immunity with Antioxidants in Patients with Thalassemia Major.
Authors: Atasever Belkis , Kuruca Serap Erdem , Karakas Zeynep , Agaoglu Leyla 
Published: October 2019

Abstract
Immunological disturbances have been reported in thalassemia and the possibility has been raised that these may be consequences of blood transfusion and iron overload. These disturbances are augmentation of the number of supressor T cells (CD8), decreased number and activity of helper T cells (CD4) and impaired activity of NK (natural killer) cells. Iron overload causes toxic tissue changes through the release of free radicals and induces oxidative stress. According to Fenton and Haber-Weiss reactions, iron plays a catalytic role occuring hydroxyl radicals (OH*) which are very reactive free radicals. Antioxidants, like vitamin E, vitamin C and selenium, may modulate oxidative damage.
In the present study; firstly, normal lymphocytes mitogen responses and NK activity were investigated by colorimetric MTT test in 26 thalassemia patients and 10 healthy volunteers as control. Secondly, lymphocytes were incubated with vitamin E ( 150, 50, 15 mg/ml), vitamin C (200, 100, 20mg/ml) and selenium (10−5, 10−6, 10−7 M). Finally, lymphocytes mitogen responses and NK activity are investigated. The results were statistically analyzed comparing with controls and healthy volunteers.
It was found decreased NK activity of thalassemia patients in comparison with healthy volunteers. The concentration of 10−7 M of selenium enhanced NK activity at the E:T (effector/target) ratio of 50:1 The concentration of 200 mg/ml of vitamin C enhanced NK activity at the E:T ratio of 10:1, 25:1 and 50:1. However, vitamin E decreased NK activity of both thalassemia patients and healhty volunteers. The concentration of 50 mg/ml vitamin E decreased NK activity at the E:T ratio of 5:1 in thalassemia patients and the concentration of 15 mg/ml of vitamin E decreased NK activity at the E:T ratio of 5:1 in healhty volunteers.
It was not found any differences between thalassemia patients and healthy volunteers in lymphocytes mitogen responses. The concentration of 200 mg/ml of vitamin C decreased lymphocytes mitogen response against PHA.
In conclusion, we suggest that vitamin C and selenium supplementation are required in patients with thalassemia for augmentation of NK cell activity.
Novel Dombrock Blood Group Genetic Variants in Different Ethnic Groups Identified by High Throughput Beadchip DNA Analysis.
Authors: Reid Marion E. , Vissavajjhala Prabhakar , Palacajornsuk Poosub , Velliquette Randall W. , Chaudhuri Asok , Hashmi Ghazala P. , Shariff Tasmia , Seul Michael 
Published: October 2019

Abstract
Background : Modern bioarray chip technology enables rapid allele determination in a large number of donors by DNA typing when compared to classical serological methods. We analyzed five single nucleotide polymorphisms (SNPs) associated with Dombrock (DO) alleles in blood samples from donors of different ethnic groups, and found new genetic variants.
Method : The BeadChip™ technology used primers for a single multiplex PCR reaction, and allele-specific oligonucleotides with variable 3′-terminal nucleotide for elongation-mediated multiplex analysis (eMAPTM) of the DO polymorphisms. Color-encoded beads displaying the elongation probes were assembled into planar arrays of small footprint on semiconductor chips, permitting the instant imaging of fluorescent elongation products from the entire array. Five SNPs of DO blood group antigens DOA/DOB (nt 378 C>T, 624 T>C, 793 A>G), Hy+/Hy− (nt 323 G>T) and Jo(a+)/Jo(a−)(nt 350 C>T) were analyzed simultaneously. Blood samples from a total of 445 donors, comprising of 100 Thai, 69 Jewish, 58 Chinese and 218 random New York City donors were analyzed.
Results : As shown in the table below, the predominant diploid allelic combinations observed in all the groups were DOB/DOB followed by DOA/DOB and then DOA/DOA. In the random donor group, we also observed several less prevalent allele combinations: DOB/HY (14.2%), DOB/JO (1.4%), DOA/HY (0.5%), DOA/JO (2.3%), HY/HY (1.4%), JO/JO(1.8%), and HY/JO (0.9%). Interestingly, two novel alleles in trans with the known alleles: DOB/HA (11% in Thai, 2.9% in Jewish, 6.9% in Chinese and 2.8% in random donors), DOA/HA (1.8% in random donors, 1.7% in Chinese and 1.4% in Jewish), DOB/SH (0.5% in random donors) and HY/SH (1.4 % in random donors) were also detected. HA allele is 378T, 624T, 793A (like JO but with 350C). Hemagglutination studies showed that HA, as predicted from the nucleotide at position 793, encoded Doa antigen. SH allele is 378C, 624C, 793C (like HY but with 323G) and is predicted to encode Dob antigen.
Conclusion: The BeadChip™ technology facilitated the identification of novel genetic variants, in addition to accelerating blood group typing.
Most prevalent DO allele combinations (in %)
Ethnic Group DOB/DOB DOA/DOB DOA/DOA Thai 73 14 2 Jewish 52.2 30.4 9 Chinese 79.3 12.1 0 Random 38.5 21.6 11
Peripheral Blood Lymphocytes Subpopulations and Apoptotic Markers in Patients with Lymphoid Malignancies and in Controls: An Epidemiologic Case-Control Study.
Authors: Maynadie Marc M. , Casey Romain , Piazzon Karine , Capiod Jean Claude , Carli Paule-Marie 
Published: October 2019

Abstract
Few references ranges of normal peripheral blood lymphocytes subpopulations are available in the literature and fewer data were available regarding activation, proliferation and apoptosis antigen expression on such populations. We studied these parameters in patients included in an epidemiologic case-control study on risk factors of lymphoid malignancies conducted within European countries.
Cell surface staining of peripheral blood lymphocyte antigens were analysed by multicolour flow cytometry in 300 cases and 300 controls. We determined CD3+, CD3+/CD4+, CD3+/CD8+, CD3−/CD56+CD16+, CD19+, CD19+/CD5+, CD19+/CD5− and CD57+ populations. Expression of CD25, CD16, CD40, CD154, CD95 and CD178 were studied on these populations. CD expressions were compared by multiple regressions between controls and diseases, after stratification on circulating phase. In controls we observed a significant decrease of B cells and an increase of NK cells with age. No difference was found according to sex, smoking status and Body Mass Index. In Follicular Lymphoma, Diffuse Large B Cell Lymphoma and Marginal Zone Lymphoma (MZL) without circulating phase cases, we observed a decrease of the B cell subset and an increase of the NK cell subset instead of only a trend was found in Multiple Myeloma, Mycosis Fongoides, Hodgkin Disease and Lymphoplasmacytic Lymphoma. CD95 expression was increased in HD, DLBCL, MZL without circulating phase and Hairy Cell Leukemia but decreased in B-cell Chronic Lymphocytic Leukemia and MZL with circulating phase. CD40 was decreased on B cells in HD, FL, MZL, B-ALL and CLL.
This study was one of the most important, in term of number of patients included, particularly concerning data on activation, proliferation and apoptosis markers in normal subjects but also in several lymphoid malignancies.
Multiple Cycles of Recombinant Human Thrombopoietin Therapy in a Patient with Chronic Refractory Idiopathic Thrombocytopenic Purpura.
Authors: Zhao Yongqiang , Hua Baolai , Zou Nong , Wang Shujie , Zhu Tienan 
Published: October 2019

Abstract
Thrombopoietin (TPO) is the key regulator of megakaryocytepoiesis and platelet production. TPO binds to its specific receptor, c-Mpl, on the surfaces of megakaryocytes, and may promote the proliferation, differentiation and maturation of megakaryocytes, and finally increase the circulating platelet count. The role of TPO in the pathogenesis of idiopathic thrombocytopenic purpura (ITP) is not certain. Plasma concentrations of TPO in ITP patients were similar to or little lower than that in healthy subjects. Therefore it is possible that supplemental TPO could significantly promote platelet production and increase platelet counts in ITP patients. Here, we report the result of multiple cycles of recombinant human thrombopoietin (rhTPO) therapy in a patient with refractory ITP. The patient, a 42-year-old woman, was admitted to our department on December 30, 2003. She had suffered from chronic ITP for more than 4 years. The patient had been treated with glucocorticosteroids, immunosuppressive agents and splenectomy. No sustained response could be achieved. The diagnosis of chronic refractory ITP was made. There were petechiae and gingival bleeding on admission. Liver and spleen were not palpable. Hemoglobin was 142g/L, white blood cell count 7.6×10 9/L, platelet count 15×10 9/L. Bone marrow aspiration revealed that erythroid and myeloid development were normal, megakaryocytes were increased in number and no dysplastic features. After an informed consent was obtained from the patient, rhTPO (Sunshine Pharmaceutical Corporation, China) was administrated subcutaneously at dosage of 1.0 μg/kg, daily for 14 days or until platelet count sustained more than 50×109/L. Anti-rhTPO antibodies were determined weekly by ELISA. Three cycles of rhTPO therapy was given with 6, 13 and 8 dosing for each cycle. The platelet counts before each cycle were all less than10×109/L and increased above 50×109/L on day 5, 11 and 8 of rhTPO administration, respectively. The peak platelet counts of 456, 130 and 82×109/L were reached on day 9, 15 and 13 for each cycle. Then platelet count decreased gradually. The durations of platelet count more than 50×109/L in 3 cycles were 13, 7 and 10 days respectively. No increase of WBC count and Hb level occurred. No liver and kidney function damage, abnormal coagulation functions or thrombosis developed during the treatment. rhTPO antibodies were not detectable. The result indicated that rhTPO could transiently increase peripheral platelet counts of the patient with chronic refractory ITP. It was uncertain why peak platelet counts declined and durations of platelet count more than 50×109/L shortened when multiple cycles of rhTPO were given.
An Open Label, Multi Center Study on the Efficacy and Safety of a Liquid, Ready-to-Use Intravenously Administered Anti-D Immunoglobulin in Patients with Chronic Immune Thrombocytopenic Purpura.
Authors: Aledort Louis M. , Salama Abdulgabar , Kovaleva Lidia , Robak Tadeusz , Brenner Benjamin , Newland Adrian , Davies Simon , Nugent Diane J. , Hubsch Alphonse , Andresen Irmgard , Zenker Othmar 
Published: October 2019

Abstract
Introduction
Intravenous anti-Rh0(D) immune globulin (anti-D) is used as a platelet enhancing therapy in patients with ITP. The following study was designed to assess the efficacy, tolerability and safety of a new, liquid anti-D (ZLB Behring).
Methods
This multicenter study was an open-label, single arm, phase III trial of 98 Rh0(D)-positive patients with chronic ITP and a platelet count < 30x109/L. Exclusion criteria included previous splenectomy, HIV infection, pregnancy, anemia (hemoglobin < 100 g/L), and positive Coombs test. The study medication was a chromatographically purified, solvent detergent treated and nanofiltered (15 nm) anti-D. This manufacturing process results in a product with a high purity (particularly a very low IgA content) and an excellent viral safety. Anti-D was provided in pre-filled, ready-to-use syringes and administered at a dose of 50 μg/kg body weight as a single intravenous injection.
The primary endpoint was the response rate, defined by the percentage of patients reaching an increase of their platelet count by at least 20x109/L to at least 30x109/L within 15 days. Secondary endpoints included time to platelet response, duration of response and the regression of hemorrhages. For the safety evaluation, blood hemoglobin, serum creatinine and bilirubin levels were closely monitored, in addition to the recording of all adverse events (AE).
Results
The overall response rate was 66 % (95 % CI: 57 to 75 %). The median time to response was 3 days and the median duration of response was 22 days. A regression of hemorrhages was seen in 88 % of the 50 patients having bleeding at baseline. The most frequent drug related AEs were chills, pyrexia, increase in bilirubin levels and headache. They were generally mild or moderate. A slight decrease in hemoglobin levels (median: -8 g/L) and a slight, transient elevation of bilirubin (median: +0.6 mg/dL) were seen in most patients as expected due the mode of action of anti-D. Clinically relevant elevations in serum creatinine level did not occur (median change: < 0.02 mg/dL).
Discussion
The present study has demonstrated that the tested anti-D is safe and efficacious in chronic ITP. Response rate, time to response and duration of response were similar to those reported for other platelet enhancing treatments, including high dose corticosteroids, IVIG and other anti-D products. The increase in platelet count was accompanied by a substantial regression of hemorrhages. Drug related adverse events were mainly mild and expected and no cases of severe hemolysis or deterioration of renal function occurred. The liquid, ready-to-use anti-D is an attractive treatment alternative in ITP, offering the convenience of a fast and easy administration.