bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect Of Maternal Cigarette Smoking On Newborn Iron Stores
Authors: Pateva Irina , Kerling Elisabeth , Carlson Susan , Reddy Manju , Chen Dan , Tancabelic Jakica 
Published: October 2019

Objective
Previous small-scale studies suggest that maternal smoking lowers neonatal body iron. Our objective was to study and compare the relationship between maternal and infants’ body iron in smokers and non-smokers in a large matched-pair cohort.

Method
This was a prospective cohort study involving 144 mothers – 72 smokers and 72 non-smokers and their respective infants. Samples were obtained from maternal blood and infants’ cord blood at delivery for serum transferrin receptor (sTfR) and ferritin levels. Serum TfR and ferritin levels were measured by RAMCO ELISA and RIA assays. The total body iron (TBI) was calculated using the sTfR/ferritin ratio.

Results
Maternal total body iron and smoking status
Women who smoked had lower sTfR, higher ferritin and higher body iron compared to nonsmoking women.
Infant’s total body iron, measurements at birth and smoking status
In contrast to their respective mothers, we found a small but statistically significant negative correlation between smoking and infants’ total body iron. The number of PPD smoked was negatively correlated with infants’ ferritin and total body iron. The number of days smoked during pregnancy was also negatively correlated with infants’ ferritin and total body iron and positively correlated with infants' sTfR.
Birth weight was lower in babies of smokers compared to nonsmokers (mean /- SD =3270 +/-475 vs. 3393 g +/- 475 g, p=0.03). Correlation studies revealed that birth weight in infants of smokers was negatively correlated with PPD smoked and number of days smoked. Birth length in the same infants was also negatively correlated with PPD smoked and number of days smoked.

Conclusion
Mothers who smoked during pregnancy had higher iron stores but their newborn infants had lower iron stores than those of non-smoking mothers. There may be a negative dose-dependent response between fetal smoke exposure and infant iron stores.

Disclosures:
No relevant conflicts of interest to declare.
Microparticle Profile During Painful Crisis and Steady State Period In Sickle Cell Anemia
Authors: Atmis Anil , Sasmaz Ilgen , Antmen Bulent Ali ,   Yurdanur - Kilinc ASH Member ID425205
Published: October 2019

Introduction
Sickle cell anemia is a disease which is characterized with hemolytic anemia, hypercoagulopathy and painful crisis. Microparticles are 0,1-1 µm sized little membrane particles which are derived during activation or apoptotic phase of cell cycle. It is reported that microparticles are increased in many systemic disease including sickle cell anemia.

Aim
In this study we aimed to investigate the role of microparticles on during crisis and non-crisis periods in sickle cell anemia patients.

Materials and method
Twenty nine patients, following by Cukurova University, Department of Pediatric Hematology, are included in this study. Blood samples were collected in 26 of these patients in non-crisis period. Control group formed with 18 healthy children without any systemic disease. Complete blood count, hemoglobin electrophoresis and biochemical parameters were studied in both groups. Also patients’ total microparticle levels, erythrocyte (CD235a), endothelial (CD106), monocyte (CD14) particle levels and tissue factor expressing (CD142) microparticle levels were studied by flow cytometry and whole data was statistically analyzed.

Findings
Hemoglobin and hematocrit levels were significantly low in sickle cell anemia patients (p<0,001). Levels of HbS were significantly high during crisis period comparing with mean HbS levels during non-crisis period (p<0,001). Total microparticle levels were significantly high in sickle cell anemia patients with painful crisis comparing with control group (p<0,05). Erythrocyte and monocyte microparticle levels were significantly high in patients with painful crisis comparing with non-crisis periods (p<0,05). Endothelial and tissue factor expressing microparticle levels were high in patiens with crisis comparing to non-crisis period but this was not statistically significant (p>0,05). There was not any significant relation with frequency of crisis and microparticle levels (p>0,05). Microparticle levels were low in patients whose were taking hydroxiurea treatment comparing with non-hydroxiurea treatment but this data was not statistically significant (p>0,05).

Result
As a result we found high levels of total microparticle, erythrocyte and monocyte microparticles in sickle cell anemia patients during painful crisis period. This important clue of crises was need further studies in order to understand the effect of microparticles on pathophysiology of sickle cell anemia.

Disclosures:
No relevant conflicts of interest to declare.
The Cerebral Vasculopathy In Malian Sickle Cell Anemia Children: Lesson From Routine Transcranial Doppler Screening
Authors: Diallo Dapa Aly , Guindo Aldiouma , Dorie Alain , Touré Boubacari Ali , Fané Baba , Sarro Yaya , Tchernia Gil 
Published: October 2019

Cerebral vasculopathy is one of the major complications of Sickle Cell Disease (SCD). 11% of the homozygous SCD patients experience stroke by age of 20 years. The use of Transcranial Doppler (TCD) allows identification of patients at risk for stroke and leads to implementation of a preventive treatment that contributes to limit the burden of SCD particularly during childhood. Using TCD screening, we evaluated the prevalence and incidence of cerebral vasculopathy in Malian SCD children. During the years 2008 to 2013, 572 children, 249 girls and 323 boys, age range (2-17yrs) were routinely screened by TCD at our Sickle Cell Disease Research and Control Center of Bamako, Mali. The overall prevalence of cerebral vasculpathy defined by conditional (1.5-1.79 cm/sec) and abnormal TCD (≥ 1.80 cm/sec) in this population is 17.1%. The highest proportion (92.9%) was observed in homozygous SCD patients while the percentage of affected patients was much lower in S/β0thalassemia (4.1%) and in SC (3.1%) patients. No cases were observed in S/β+thalassemia patients. SCD children <9 years old were more susceptible to cerebral vasculopathy complications than those above this age threshold (P<0.001). Low hemoglobin levels and low fetal hemoglobin were associated with an increased risk of cerebral vasculopathy. During the study, 4 of 444 children with normal TCD converted to conditional TCD, while 5 of 68 children with conditional TCD converted to abnormal TCD. This conversion from conditional to abnormal TCD was associated with a mean decrease in Hb value of 0.37g/dL (P=0.002). In conclusion this study shows high prevalence and incidence of cerebral vasculopathy in Malian SCD children. While chronic transfusion programs significantly reduces the risk of stroke in SCD patients with abnormal TCD, at present there are no well articulated strategies to prevent conversion from conditional to abnormal TCD. A more comprehensive approach would hopefully reduce the morbidity and mortality due to cerebral vasculopathy in SCD affected children.

Disclosures:
No relevant conflicts of interest to declare.
Thalassemia and Hemoglobinopathy Screening By HPLC Method and Comparison With Conventional Methods
Authors: Hosseeini Soudabeh , Kalantari Ebrahim , Dorgalaleh Akbar , Bamedi Taregh , Farzi Massomeh , Saeed Dorgalele 
Published: October 2019

Background
Thalassemia and hemoglobinopathies are heterogeneous group of inherited disorders that affects men and women equally. HPLC is a valuable method for hemoglobinopathy and/or thalassemia carrier screening. This study evaluate the role of cation exchange HPLC along with adjunctive tests as needed in the diagnosis of thalassaemias/haemoglobinopathies and to see the frequency of these disorders in the Iranian population.

Methods
This five-year study was conducted on 3780 patients. Initially complete blood count was done by autoanalyzer and then for detection of abnormal hemoglobins HPLC and HB electrophoresis methods was used. In cases with low MCV and MCH indices (MCV<80 fl,MCH<27 pg) and Hb-A2< 3.5% and normal Hb-electrophoresis, α-thalssemia trait(αα/--)was considered in the list of differential diagnosis. In cases with low MCV for exclusion of iron deficiency serum ferritin was meseared.

Results
Our rerults revealed that 1932 (51.11%) had normal electrophoretic pattern, 781 (20.66%) had β-thallasemia trait and 487(12.84%) had β-thallasemia major or intermedia,328( 8.67% ) had normal electrophoresis along with iron deficiency and 142 ( 3.75%) had normal Hb -electrophoresis and normal iron status but low MCV and MCH indices.We also identified 11(0.29%) with Alpha thalasemia variants Hb-H disease/alpha trait and 22(o.58%)with sickle trait and 18(o.47%)with sickle disease and 9(0.23%) S-Thal double heterozygote and 5(0.13%) with E- trait and 32(0.84%) with Hb-D variant and 1(0.026%) with heterozygote Hb-C variant and 5(0.13%) with Hb-D Iran and 1(0.026%) with Hb-J trait and 1(0.026%) Hb-S/D double heterozygote, and 1(0.026%) with Hb-D/J double heterozygote and 1(0,026%) with Hb-constant spring/ HB-H double heterozygote.

Conclusion
HPLC is a fast and reliable method in clinical laboratories specially in premarital, and neonatal screening laboratories.

Disclosures:
No relevant conflicts of interest to declare.
Substrate Reduction Therapy With Miglustat In Type 1 Gaucher Disease In Spain. Nine Years Outcomes Update On ZAGAL Study
Authors: Giraldo Pilar , Andrade Marcio M , Medrano Blanca , Alfonso Pilar , Irún Pilar , Atutxa Koldo , Fernandez-Galan Angeles , Barez Abelardo , Franco Rafael , Roig Inmaculada , Giner Vicente , Villalon Lucia , Martinez-Estefano Elisa , Luño Elisa , Loyola Ines , Salamero Olga , la Serna Javier de , Pocovi Miguel 
Published: October 2019

Substrate reduction therapy (SRT) has showed as an useful therapy in type 1 GD patients with mild or moderate disease. The main limitation to use miglustat has been the gastrointestinal adverse events. Since 2004 we have conducted the ZAGAL (Zavesca en Gaucher Leve) study for monitoring the real-life use of miglustat in Spanish adult patients with mild-to moderate disease. The study included GD1 patient’s naïve to therapy as well as patients who have previously been treated with ERT. For follow-up, the therapeutic goals for GD therapy by Pastores GM et al were applied.
To date a total of 351 GD1 patients have been diagnosed in Spain (FEETEG unpublished. 2013); from 2004 until 2013, 53 of them have been exposed of miglustat (15.1%). In 16 patients (30.2%) miglustat was the first line of therapy and the remaining 38 switched from ERT.
Currently 37 patients (mean age 43.6 y, range 22-83) 50.9% females, are on miglustat therapy (20 at least for 5 years and 13 during more than 8 years). Related to efficacy, the therapy permit to achieve a stable hemoglobin concentration level and spleen reduced volume, but we recorded a decrease of absolute platelet count in 15 patients (28.3%) (mean: 35x109/L, range: 10-86x109/L). Related to biomarkers changes an increase in CT activity was observed in 56.6% of patients (mean: 2,448 nmol/mL.h, range 135-13,687) and 43.4 % for CCL18/PARC (mean: 250 ng/mL, range: 19-1016). Seventeen patients (32.1%) had transitory gastrointestinal disturbances. Sixteen patients (30.2%) discontinued therapy: one of them for pregnancy, two by bone crisis, two by weight loss, one for bad compliance and ten by gastrointestinal discomfort or intolerance (18.8%). 60% of patients has a fine tremor in first months on therapy. 4 died by non-related causes (2 cancer, 1 hearth attack, 1 liver failure),

Conclusion
The long term follow-up of GD patients treated with Miglustat shows that more than 69% had achieved and maintains the therapeutic goals. A high individual variability had been observed related to miglustat gastrointestinal intolerance apparently no related with GBA genotype, gender and age, but possibly associated with disacaridases inhibition and food habits.

Disclosures:
No relevant conflicts of interest to declare.
The Profile Of The T Helper, Cytotoxic T and Natural Killer Cells In Sickle Cell Anemia Patients With Ischemic Attack and The Relation With Clinical Prognosis
Authors: Kilinç Yurdanur , Atmis Bahriye - , Atmis Anil , Yilmaz Mustafa , Sasmaz Ilgen , Karagün Barbaros Sahin 
Published: October 2019

Purpose
The study is conducted in 29 sickle cell anemia (SCA) patients, who are in ischemic attacks (in vasoocclusive crises period) and in steady state; the level of T helper cells, cytotoxic T cells and natural killer cells were determined and the effect of ischemic attack on clinical prognosis and the immune functions.

Materials and Methods
In the study, 29 patients with sickle cell anemia in ischemic attacks with painful crises and in steady state and 24 healthy children were chosen in the same age group for control group. These groups were examined with complete blood cells count, Hb electrophoreses and the blood biochemistry. The study was performed by flowcytometric method to find the level of CD3 monoclonal antibody for total T lymphocyte, CD4 monoclonal antibody for T helper cells, CD8 monoclonal antibody for cytotoxic T cells and CD16+56 monoclonal antibodies for natural killer cells in the mentioned groups to compare the statistical data.

Findings
The average of HbS in ischemic periods in SCA patients are to be found 83±6,6 %. There were decrease in hemoglobin and hematocrit levels in SCA versus control group (p<0,001). The levels of CD3 are lower in SCA patients with crises period (62,31±7,79 %) than in steady state (65,53±5,72 %) and in control group (69,09±9,18 %) (p=0,007). The natural killer cells in crisis period (13,07±7,67 %) and in steady state (12,71±5,62 %) were lower than in control group (8,11±4,67 %) (p=0,009). In SCA patients, the level of CD3,CD4, CD8 and CD16+56(+) T cells are not changed with the frequency of crisis (p>0,05).

Results
As a result of the study, in the patients with sickle cell anemia whom associated with chronic hemolysis and tissue hypoxia during the ischemic attack, the levels of total T lymphocyte (CD3) was found significantly lower than the control groupp<0.001. The levels of T helper cells (CD4) and cytotoxic T cells (CD8) did not differ between SCA patients and control group. The levels of natural killer cells (CD16+56) was found higher in crises period and steady state than control group. To find the T cell subset levels in clinical and prognostic effects in SCA, it is necessary to do study with bigger groups of patients and wide range of study.

Disclosures:
No relevant conflicts of interest to declare.
Self- and Parent/Proxies-Reported Health-Related Quality Of Life In Children and Adolescents With Bleeding Disorders: Cross Sectional Investigation and Comparison With Healthy Siblings and Healthy Peers
Authors: Bruno Neuner , von Mackensen Sylvia , Halimeh Susan , Holzhauer Susanne , Klamroth Robert , Kurnik Karin , Kruempel Anne , Fruewald Michael , Krampe Henning , Nowak-Goettl Ulrike 
Published: October 2019

Background
Hereditary bleeding disorders (HBD) affect children from birth during their life course. Medical treatment and the overall prognosis of children with HBD have significantly progressed. But even in patients cared for in specialized treatment centers it remains unclear whether survival till adulthood goes along with health-related quality of life [Hr-QoL] comparable to other patients groups respectively comparable to population children. Therefore aim of the present study was to assess self- as well as parents/proxies reported Hr-QoL in children and adolescents with HBD and to compare the results with findings from children affected by another chronic medical condition respectively with healthy siblings and peers.

Methods
91 patients with HBD (thrombosis / deep venous thrombosis, DVT, respectively Haemophilia A and B) aged 8 to 16 years from 6 Hemophilia study centers were investigated regarding Hr-QoL. Hr-QoL was assessed in patients and parents/proxies with the generic KINDL-R questionnaire exploring overall well-being and 6 sub-dimensions (physical well-being, psychological well-being, self-esteem, family-related well-being, friend-related well-being, and school-related well-being). Findings were compared with 70 children with stroke / TIA respectively with healthy controls (45 healthy siblings and 106 healthy peers).

Results
Overall well-being in children with thrombosis / DVT (77.6 ± 9.7 points) was comparable to healthy controls but in children with Haemophilia A or B (76.0 ± 9.6) lower compared with healthy peers (80.2 ± 9.7, p = 0.005). No differences occurred between healthy controls and children with stroke/TIA (74.2 ± 10.3). In children with HBD none of the KINDL-R sub-dimensions showed values below healthy siblings. Two KINDL-R sub-dimensions showed lower values compared with healthy peers. Parents/proxies rated the Hr-QoL of their children with HBD similar to their healthy children. The internal consistency of overall well-being in all study subgroups was acceptable (> 0.7) but showed poor results (< 0.5) in two KINDL-R sub-dimensions.

Discussion
The application of a generic Hr-QoL questionnaire in a sample of children and adults with HBD seems feasible. Their Hr-QoL seems comparable to their siblings but below their healthy peers.

Disclosures:
Halimeh: Octapharma AG: Investigator Other, Research Funding.
High-dose melphalan and granulocyte-macrophage colony-stimulating factor for refractory multiple myeloma
Authors: Barlogie B , Jagannath S , Dixon DO , Cheson B , Smallwood L , Hendrickson A , Purvis JD , Bonnem E , Alexanian R 
Published: October 2019

Abstract
High-dose melphalan has induced remissions in about 40% of patients with refractory myeloma, but the mortality has been high, at about 20%, due to complications of prolonged granulocytopenia. In an attempt to stimulate earlier granulocyte recovery, recombinant human granulocyte- macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously to 23 patients with refractory myeloma who had been treated with melphalan at a high dose of 100 mg/m2. Thirty-nine percent of patients achieved marked tumor cytoreduction by at least 75%, 2 died within 2 months from infectious complications during severe neutropenia; and median durations of relapse-free and overall survival were 7 and 10+ months, respectively. The nine patients presenting with both advanced age over 50 years and a long history of prior therapy of over 1 year required significantly longer median times of 31 days for granulocytes and of 63 days for platelets to reach safe levels of at least 500/microL and 50,000/microL, respectively, than the 14 remaining patients who had none or only one of these adverse features (21 and 26 days, respectively). In a historic control of 43 patients treated previously with high-dose melphalan but without GM-CSF, hematologic recovery to the aforementioned levels of granulocytes and platelets proceeded over almost 5 weeks, regardless of age and prior treatment exposure. Thus GM-CSF seems to hasten marrow recovery, especially in patients with adequate normal marrow stem-cell reserve as defined by younger age or less prior therapy. While not shortening the duration of neutropenia, GM-CSF dose increments (from 0.25 to 0.5 to 0.75 mg/m2) increased the incidence of severe toxicity from 0% to almost 40%, especially among older patients. These results support the usefulness of low-dose GM-CSF (0.25 mg/m2) in stimulating marrow recovery in selected patients with adequate marrow reserve treated with high-dose melphalan for refractory multiple myeloma.
Quinine-induced immune thrombocytopenia associated with hemolytic uremic syndrome: a new clinical entity
Authors: Gottschall JL , Elliot W , Lianos E , McFarland JG , Wolfmeyer K , Aster RH 
Published: October 2019

Abstract
Three patients are described who developed severe thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure after ingestion of quinine. In one patient, the same clinical findings recurred several months later after another exposure to quinine. Serum from one patient contained quinine-dependent IgG antibodies reactive with the platelet glycoprotein (GP) Ib/IX complex. In the second and third cases, serum contained IgG and IgM antibodies reactive with both the GP Ib/IX and IIb/IIIa complexes in the presence of quinine. Quinine appears to have induced both immune thrombocytopenia and the hemolytic uremic syndrome (HUS) in these individuals. Findings made in these cases may have implications for the pathogenesis of some forms of HUS.
Mutations of the p53 gene in lymphoid leukemia
Authors: Sugimoto K , Toyoshima H , Sakai R , Miyagawa K , Hagiwara K , Hirai H , Ishikawa F , Takaku F 
Published: October 2019

Abstract
p53 is currently considered to be a tumor suppressor gene product, and its alterations are suggested to be involved in several human malignancies. Here we show evidence of the possible involvement of p53 gene mutations in lymphoid leukemias studied by reverse transcriptase- polymerase chain reaction, single strand conformation polymorphism analysis, and nucleotide sequencing. Fourteen patients with various leukemias were examined and two with acute lymphoblastic leukemia and one with Waldenstrom's macroglobulinemia were identified to have mutations in the coding region of the p53 gene. These mutations included point mutation, triplet deletion, and single nucleotide insertion. Furthermore, expression of the wild-type p53 mRNA was not detected in the samples from these three patients. In one of them, chromosome 17p was deleted, suggesting the absence of the nonmutated p53 gene, whereas in the other two patients, chromosome 17p seemed to be intact by cytogenetic analysis. Our results suggest that alterations of the p53 gene may have a role in the genesis of some leukemias.
Effects of thymidine and hydroxyurea on the metabolism and cytotoxicity of 1-B-D arabinofuranosylcytosine in highly resistant human leukemia cells
Authors: Bhalla K , Swerdlow P , Grant S 
Published: October 2019

Abstract
We have examined the effect of the ribonucleotide reductase inhibitors thymidine (dThd) and hydroxyurea (HU) on the metabolism and cytotoxicity of high concentrations (10 to 100 mumol/L) of cytosine arabinoside (Ara-C) in a deoxycytidine kinase-deficient, highly Ara-C- resistant human promyelocytic leukemic cell subline (HL-60/Ara-C). Administration of dThd or HU (0.5 to 3 mmol/L) in conjunction with high concentrations of Ara-C either sequentially or simultaneously lead to enhanced (and in some cases a supra-additive) inhibition of HL-60/Ara-C suspension culture growth and soft agar colony formation. In addition, exposure of cells to 0.5 mmol/L dThd or HU for 48 hours significantly increased the percentage of HL-60/Ara-C in S-phase. In contrast to previous studies involving low-dose Ara-C administration, we were unable to detect dThd- or HU-mediated increments in Ara-CTP formation in HL-60/Ara-C cells treated with high-dose Ara-C despite reductions in intracellular dCTP pools as great as 65%. However, dThd or HU did increase Ara-C incorporation into newly synthesized DNA. These studies show that administration of dThd or HU in conjunction with high concentrations of Ara-C results in an enhanced antiproliferative effect of Ara-C against Ara-C-resistant leukemic cells deficient in deoxycytidine kinase.