bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of α-Thalassemia and Iron Deficiency in the Difference between Hemoglobin Levels of African-Americans (AA) and Whites.
Authors: Beutler Ernest , West Carol 
Published: October 2019

Abstract
The fact that the average hemoglobin concentration (Hb) of AA is lower than that of whites has been documented extensively. Several investigations have shown that this difference of approximately 0.8 g/dL is due neither to iron deficiency nor to socioeconomic status. Its cause remains unknown. We compared the Hb of 1,493 AA and 31,029 white anonymized patients attending a Health Appraisal Clinic and confirmed the known difference in Hb, both for females and males (0.79 and 0.47 g/dL) respectively. The difference persisted when a subset of the subjects were paired by age and narrowed slightly in females when those with serum ferritin levels of <10 ng/ml or transferrin saturations of <16% were excluded (difference in females 0.59 g/dL; males 0.47). We determined the α-thalassemia −3.7 genotype of 298 AA. The gene frequency was found to be 0.17, and the distribution of genotypes fit the Hardy-Weinberg equilibrium. However, in a sample of 155 white subjects only one α-thalassemia allele was found (gene frequency=0.003). Among the AA subjects, the Hb and MCV values were lower in homozygotes (−a/−a) and heterozygotes (aa/−a) for α-thalassemia than in the aa/aa subjects. The table presents data for AA and white subjects after excluding all who did not have a documented serum ferritin level of >9 ng/ml and a transferrin saturation of >16%. Excluding subjects with sickle trait had no effect.
Ethnic Group Genotype n Mean Hb SE Hb Mean MCV SE MCV −a/−a 3 11.87 0.418 72.23 2.32 F AA aa/−a 20 12.69 0.202 85.22 0.86 aa/aa 65 13.17 0.127 90.43 0.61 White 2917 13.60 0.016 90.85 0.07 −a/−a 2 13.85 0.550 83.05 1.65 M AA aa/−a 36 14.37 0.161 85.81 0.78 aa/aa 86 14.75 0.123 89.78 0.53 White 5335 15.09 0.013 90.35 0.06
As shown in the table, the average Hb of non-iron deficient AA females and males who had 4 normal α loci (aa/aa) was 0.43 and 0.34 g/dL lower respectively than those of whites, the difference being significant with p<0.01. We conclude that one cause of the lower Hb of AA compared to white subjects is the high prevalence of α-thalassemia in the AA population, but that it accounts for only about one-quarter of the difference after iron deficiency has been excluded. There are other, as yet undefined, causes that play a role. These may include the lower ATP (Biochem. Genet.1:25, 1967) and higher 2,3 BPG (Transfusion18:108, 1978) levels that have been documented in the red cells of AA subjects.
Correlation between Leg Ulceration and Perforator Venous Insufficiency (PVI) in Patients (Pts) with Sickle Cell Disease (SSD).
Authors: Braverman Albert , Nehra Anupama , Gillette Peter , Weedon Jeremy , McGagh Deidre , Olivier Tracy , Gwertzman Gary , Deitch Jonathan 
Published: October 2019

Abstract
Chronic or recurrent leg ulceration occurs in 25% of adult SSD pts, but as many as 75% never develop leg ulcers. PVI correlates with leg ulceration in non-SSD pts. We studied 46 SSD pts: 40 with hemoglobin (Hb) SS, 3 with sickle-b thalassemia, 2 with Hb SC and 1 with Hb SD. Chronic and/or recurrent leg ulceration was present on at least 1 leg of 25/46 (ulcer+) and absent in 21/46 (ulcer-) SSD pts. Their ages ranged from 19–67 years, with a median of 31. Using color-flow venous duplex (7–5 mega-Herz probe; Advanced Technology Laboratory 5000), the status of perforator veins in both legs of each pt was determined (only one of a single pt’s two ulcerated legs was studied). Perforator veins were considered incompetent (PVI) if their diameter was >3 mm, and their reflux times were >0.35 seconds. For the 36/91 ulcer+ and 55/91 ulcer- legs, there was a significant association between PVI and ulceration in the same leg (generalized mixed linear model, p=0.002). Estimated probability of ulceration in a non-PVI leg was 0.20 (95% confidence interval [0.10, 0.36]); estimated probability of ulceration in a PVI leg was 0.61 (95% CI [0.41, 0.79]). Odds ratio was 6.2 (95% CI [2.0, 19]). The prevalence of ulceration in either leg, among 22 pts with PVI in at least 1 leg, was compared with that among 23 pts with PVI in neither leg (omitting the pt with one unstudied leg). There was significant association between ulceration in either leg and PVI in either leg (Fisher’s exact test p<0.001). Estimated probability of ulceration in either leg when neither leg had PVI was 0.22 (95% confidence interval [0.07, 0.44]); estimated probability of ulceration in either leg when either leg had PVI was 0.86 (95% CI [0.65, 0.97]). Odds ratio was 23 (95% CI [4.7, 110]). PVI may be involved in the pathogenesis of leg ulceration in pts with SSD.
Blood Mononuclear Cells and Platelets Have Abnormal Fatty Acid Composition in Homozygous Sickle Cell Disease.
Authors: Okpala Iheanyi , Ren Hongmei , Ghebremeskel Kebreab , Ugochukwu Cynthia , Ibegbulam Obike , Crawford Michael 
Published: October 2019

Abstract
Leukocyte adhesion to vascular endothelium contributes to vaso-occlusion and widespread organ damage in sickle cell disease (SCD). Previously, we found high expression of the adhesion molecules αMβ2 integrin and L-selectin in HbSS individuals with severe disease. The n-6 and n-3 polyunsaturated fatty acids (FA) are vital structural and functional components of cell and sub-cellular membranes. They modulate cell adhesion, inflammation, aggregation and vascular tone. We investigated the FA composition of mononuclear cells (MNC) and platelets of HbSS patients in steady-state (n = 28); and racially matched, healthy HbAA controls (n = 13). MNC phospholipids of the patients had low levels of docosahexanoic acid (DHA, p<0.01), n-3 metabolites (p<0.05) and total n-3 polyunsaturated FA (p<0.05); table 1. In contrast, arachidonic (AA, p<0.005), AA:DHA ratio (p<0.005, fig 1) and total n-6 metabolites (p<0.05) were increased in the patients. Similarly, platelets from HbSS patients had low levels of eicosapentanoic acid (EPA, p<0.05), and raised AA (p<0.05) in choline phosphoglycerides (CPG); with reduced linoleic acid (LA, p<0.005) and DHA (p<0.05) in ethanolamine phosphoglycerides. Platelet CPG had lower DHA levels in HbSS individuals with complications of SCD compared to those who had no complications (p<0.05, fig.2). Reduced EPA and DHA relative to AA favours the production of aggregatory and pro-inflmmatory eicosanoids that activate leukocytes and platelets. This may lead to enhanced inflammation, leukocyte adhesion, platelet aggregation and vaso-occlusion in SCD.
Table 1: Fatty Acid Composition of MNC Total Phospholipids in HbSS Patients and HbAA Controls
Fatty Acids HbSS Patients HbAA Controls Values are Means [SD}. *p<0.05, **p<0.01, ***p<0.005, ****p<0.001 24:0 0.71 [0.30]*** 1.3 [0.4] saturates ∑ 38.2 [3.6] 39.1 [1.7] 16:1 0.69 [0.45] 0.56 [0.11] 18:1 14.4 [1.8]* 12.9 [1.9] 24:1 1.2 [0.3] 1.1 [0.4] ∑monoenes 16.2 [2.1]** 14.3 [1.4] 18:2n-6 6.1 [0.9] 7.0 [1.4] 18:3n-6 0.11 [0.04]* 0.23 [0.17] 20:2n-6 0.56 [0.18]** 0.83 [0.32] 20:3n-6 (DHGLA) 1.2 [0.2]* 1.4 [0.2] 20:4n-6 20.2 [1.7]*** 18.1 [1.8] 22:4n-6 1.7 [0.4] 1.6 [0.4] 22:5n-6 0.3 [0.21] 0.24 [0.14] n-6 metabolites ∑ 24.1 [1.9]* 22.6 [1.7] n-6 ∑ 30.2 [2.0] 29.7 [2.2] 20:5n-3 (EPA) 0.43 [0.16] 0.61 [0.35] 22:6n-3 (DHA) 1.9 [0.4]** 2.5 [0.6] ∑n-3metabolites 4.3 [0.9]* 4.8 [0.4] n-3 ∑ 4.5 [0.9]* 5.0 [0.4] DHGLA:AA ratio 0.06 [0.01]**** 0.08 [0.01] AA:EPA ratio 52.4 [20.9] 38.6 [18.4]
Detection of Acute Chest Syndrome by MRI in a Sickle Transgenic Mouse Model.
Authors: Kennan Richard P. , Alleyne Dawn , Aldrich Thomas K. , Suzuka Sandra M. , Renick Robert , Nagel Ronald L. , Fabry Mary E. 
Published: October 2019

Abstract
Acute chest syndrome (ACS) is a potentially deadly complication in sickle cell patients, particularly in young adults. In patients younger than 17 years, ACS is frequently associated with infection; however, in adults, association with vasocclusive crisis and fat and bone marrow embolism is more common. We have developed a sickle transgenic mouse model for ACS that consists of injecting a mixture of bone marrow and mouse fat into the tail vein of a sickle transgenic mouse. The mouse used was a NY1 partial KO that expresses 100% human α and 55% βS. Mice were injected with bone marrow (BM) from two femurs (about 15 mg) and, as murine BM lacks fat, purified peritoneal fat (about 15 mg). Creatine kinase (CK), predominantly the MM form, and sVCAM increased above baseline levels at 6, 24, and 48 hours in NY1 partial KO mice, but not in control C57Bl mice. Magnetic resonance imaging (MRI) was performed at 48 hours after the initial injection. It is normally difficult to perform MR imaging of lung due to its inherently short transverse relaxation time and relatively low proton density relative to other tissue. However, these difficulties can be overcome through the use of ultra short echo time spin echo sequences at high field strength. Spin echo images were obtained using a respiratory-gated spin echo sequences at TE=3 msec and at TE=10 msec. From this data one can calculate a quantitative relaxation rate (1/T2) map and an average value of R2. Decreased values for mean R2 are an indication of fluid accumulation. In NY1 partial KO mice examined 48 hours after injection, the 1/T2 map revealed focal patches with high water content and a mean R2 of 131 vs R2 = 220 for an uninjected control mouse; when the same animals were examined three months later R2s were found to be 181 and 124. C57Bl control mice were also examined at 48 hours post injection, and R2 values of 211 and 178 were found. Pulmonary edema is a defining finding in ACS and its presence in sickle mice, but not in control mice is strong support for this model. The mice survived both the fat/BM injection and the MRI, indicating that it will be possible to obtain repeated images from the same animal to study the natural course of lung injury and interventions that may ameliorate injury.
Barriers to Deferoxamine Adherence for Adults with Sickle Cell Disease.
Authors: Treadwell Marsha , Sung Jennifer , Murray Eileen , Hagar Robert , Major Kimberly , Hackney-Stephens Ekua , Glendenning Alastair , Hoehner Christy , Vichinsky Elliott P. 
Published: October 2019

Abstract
Background: The barriers to adherence with chelation therapy for chronically transfused and iron overloaded patients with sickle cell disease (SCD) have been described only anecdotally.
Objectives: To describe barriers to home deferoxamine (DFO) administration adherence among adults with SCD. It was hypothesized that barriers would include limited patient education on the importance of chelation and perceived aversiveness of the regimen.
Methods: Medical records were reviewed for 189 adult patients seen at a comprehensive sickle cell center. Patients with transfusion induced hemosiderosis, defined as a serum ferritin ≥ 1500 ng/ml, were administered a four item interview asking if iron overload had ever been discussed with them; if they had been informed they were iron over loaded; if chelation therapy had been offered; and if not currently home chelating, why not. Patients not interviewed were deceased (3); unavailable (10); or declined (3). A study coordinator who did not provide clinical care conducted the interviews.
Results: 54 of the 189 patients (29%) had a history of intermittent or chronic transfusion, or pheresis. 45 of these patients were iron overloaded. 29 of these patients agreed to complete the interview; 22 (76%) were female. Average age was 41.5 years (range 22.4 – 58.4 years) and average serum ferritin was 4240.8 (range 1547 – 9420). 23 of the 29 patients (79%) reported that their physician or nurse had discussed iron overload and chelation with them. 16 of these (55%) reported that they were currently receiving home DFO therapy. Reasons given for not administering home DFO included:
Reason Number (%) “Don’t want to stick self” 3 (23) No longer being transfused or being exchanged 3 (23) Awaiting clinical trial for oral chelator 2 (15) Home situation too complex 2 (15) Don’t want to (no further explanation) 2 (15) Too many adverse effects 1 (8)
Discussion: Life threatening levels of iron overload were observed in intermittently transfused adult sickle cell patients. Contrary to expectations, iron overload and its treatment had been discussed with most patients. However, just over half were currently chelating at home. Toxicity of DFO and misunderstanding that iron overload is no longer a problem if chronic transfusion therapy stops are the most common reasons for non-compliance. Repeated patient counseling are essential in order to prevent progressive iron toxicity in sickle cell disease.
Reason Number (%) “Don’t want to stick self” 3 (23) No longer being transfused or being exchanged 3 (23) Awaiting clinical trial for oral chelator 2 (15) Home situation too complex 2 (15) Don’t want to (no further explanation) 2 (15) Too many adverse effects 1 (8)
Genetic Analysis of Candidate Modifier Polymorphisms in β-Thalassemia/Hb E Patients.
Authors: Fucharoen Suthat , Winichagoon Pranee , Sripichai Orapan , Munkongdee Thongperm , Kumkhaek Chutima , Vichitumaros Kanjana , Whiacre Johanna , Abel Ken , Braun Andreas 
Published: October 2019

Abstract
β-Thalassemia/Hb E patients encompass a number of clinical severities, ranging from nearly asymptomatic to transfusion-dependent thalassemia major. This has been well documented, but the causes of the variability and the molecular basis of the interaction remain unexplained. In general any factor capable of reducing the degree of alpha-globin-beta-globin chain imbalance will result in a milder form of thalassemia. The major modifying factors demonstrated in the mild cases are coinheritance of mild β+-thalassemia and Hb E genes, coinheritance of α-thalassemia and increased production of Hb F. However, the fact that many patients who have seemingly identical genotypes, β0-thalassemia/Hb E, and do not have a detectable α-thalassemia or increased Hb F production still have mild clinical symptoms, while other patients have a very severe clinical condition similar to homozygous β0-thalassemia. This variation suggests that other unknown modifying genetic factors may contribute to severity of the disease.
To assess the relative contribution of genetic factors in the variation of severity among β-thalassemia/Hb E patients, we conducted a prospective study searching for modifying factors in almost 1100 Thai/Chinese β0-thalassemia/Hb E patients from Thailand using an automated, chip-based platform based on mass spectrometry (Sequenom’s MassARRAYTM system). A map of ~80 single nucleotide polymorphisms (SNPs) has been constructed spanning more than 80 kb, including the locus control region (LCR) and all beta-like globin genes. These SNPs were identified through resequencing and from the public domain, including well-characterized restriction fragment length polymorphisms (RFLPs) used in prior haplotype studies. Included in this panel are assays for polymorphic sites reported to influence globin gene expression, specifically Gγ-Xmn I polymorphism and BP-1 binding site upstream of β-globin gene. Genotyping of other candidate modifier loci, including SNPs in genes encoding alpha hemoglobin stabilizing protein (AHSP), β-globin gene repressor BP-1 protein, erythropoietin (Epo), and transcription factors; GATA-1, EKLF, NF-E2, has been studied. To identify additional modifier loci, carefully selected patient sub-groups representing the extremes in disease severity either mild or severe have been selected for DNA pool construction to be used in a genomewide screen involving up to 100,000 validated gene-based SNPs. It is expected that this genomewide screen will yield important information on the role of candidate genes and may uncover the association of novel polymorphisms with severity heterogeneity in β-thalassemia/Hb E disease.
Transfusion Transmitted Viral Infections in Transfusion Dependent Patients with Thalassemia in Turkey: A Multicenter Study.
Authors: Sonmezoglu Meral , Aydinok Yesim , Canatan Duran , Turker Meral , Gulen Huseyin , Irken Gulersu , Karakas Zeynep , Uysal Zumrut L. , Aydogan Gonul , Cengiz Ozcan , Timur Cetin , Apak Hilmi , Canpolat Cengiz , Bayik Mahmut M. 
Published: October 2019

Abstract
Thalassemia Major (TM) represent one of the largest groups requiring regular transfusions lifelong. A total of 3830 patients are currently registered with homozygous b-Thalassemia in Turkey. This study is designated to reveal the seropositivity status of thalassemia patients on chronic transfusion treatment for blood-borne infections. A questionnaire inquiring the demographics and medical history of the patients as well as serological status for hepatitis B, C and HIV, was sent to 12 Thalassemia Centers which are generally settled down in the University or big government hospitals with high capacity blood banks where the packed red cells were provided. The collected data of 999 patients who have regular transfusions of 1–2 Unit red cells, every 3–4 weeks beginning from the first years of life and screened for transfusion transmitted viruses (TTV) 6 monthly was analyzed. The patients were aged between 0–53 years (median 16 years). Overall HBsAg and Anti-HCV positivity were found 2.5% and 12.6% respectively. Confirmed Anti-HIV positivity was 0.2% in the study group and consistent with the low frequency of the disease among blood donors in Turkey. Age distribution of sero-positivity within the patients was as follows: 0.7% in 0–5 years, 17% in 6–10 years, 48.3% in 11–20 years and 34% over 21 years, indicating the strong relation between the sero-prevalence of TTV and transfused blood volume and the gradually increased safety of blood in Turkey. The highest prevalence rate was seen in the age of 11–20 years which also represents highest number of patients. Donated blood screening for HBsAg, anti-HIV 1/2 (since 1985), anti-HCV (since1996), and RPR for syphilis is obliged by law in Turkey. Although, widespread use of HBV vaccination in transfusion dependent patients has been started since 1990s, the data confirmed that this measurement is insufficient alone for eradicating the HBV transmission in this group. Vaccination against HBV has been scheduled routine vaccination program of infancy by the health authority since 1999. However, the positive reflection of this policy in blood safety would be seen in the next generations. In that point of view, vaccination against hepatitis B can be practised in blood donors as a preventive measure in Turkey which is considered as in the middle endemic region regarding hepatitis B infection. Although, Anti-HCV screening in blood donors caused significant decrease in HCV infection, it still represents the main cause of morbidity following cardiomyopathy in this group of patients. This study clearly shows that the threat of TTV infections among multi-transfused thalassemia patients and underlines the importance of strengthen blood donor selection and implementing the sensitive screening assays for TTV at blood centers.
The Value of Immediate Determination of C-Reactive Protein in the Hematology-Oncology Clinic.
Authors: Shah Vinay M. , Nguyen Hanh T.H. , Ramos Mercedita , Tisman Glenn 
Published: October 2019

Abstract
CRP is named such for its ability to precipitate the somatic C-polysaccharide of Streptococcus pneumoniae. This polypeptide acute phase reactant is a sensitive systemic marker of inflammation, malignancy and tissue damage. ABX Diagnostics developed a hematology analyzer (Micros CRP), which rapidly measures 16 routine hematological parameters plus whole blood CRP. The CRP value, determined by specific antigen-antibody induced optical turbidity, is available within 5 minutes with sensitivity to 0.10 mg/dl. Normal whole blood values range between 0.0 to 0.2 mg/dl. We evaluated the added clinical benefit of immediate CRP determinations in an outpatient cancer clinic in 155 patients undergoing observation and aggressive chemotherapy. Blood was obtained from all patients each visit and routine CBC, Platelet count and CRP were recorded, immediately provided to the physician in the presence of the patient and automatically stored in a database (HemaLink). Correlations were made between changes of CRP, WBC, AGC, and clinical condition. Routine measurement of CRP and its immediate availability for clinical interpretation was found to add a valuable new diagnostic dynamic for cancer patient care. Elevated CRP and its relative change were found to be a leading indicator of serious and frequently subclinical infection and were the earliest clues when compared to WBC or AGC. Relative changes of CRP were found to be indicative of clinical course. Diagnostic value of the WBC in cancer patients was lost in those undergoing myelosuppressive therapy and in those receiving leukocyte colony stimulating factors. The immediate availability of CRP allowed for preemptive diagnostics and therapy. Real-time knowledge of CRP either changed or significantly influenced therapy in 38% of patients. Study supported in part by ThinkTwice Technologies.
Functional Assessment in Myelodysplasia- Numerical Recovery of Neutrophils May Be Insufficient for Adequate Neutrophil Function.
Authors: Schiller Gary J. , Durna Lara , Koeffler H. P. 
Published: October 2019

Abstract
Myelodysplastic syndromes are a group of oligoclonal hematologic disorders characterized by variable cytopenias and dysplastic changes in the bone marrow. Novel, remittive therapies designed to treat the cytopenias of myelodysplasia, induce apoptosis, differentiation, and antiangiogenesis, in vitro. The success of remittive therapy for myelodysplasia typically depends on clinical criteria of hematopoietic recovery but seldom address functional disturbances. We present a case of an 81 year old man with a one-year history of mild pancytopenia (ANC 0.7 x 103/μL, Hemoglobin 10.3 g/dl MCV 101.7, platelets 51 x 103/μL). A bone marrow biopsy at diagnosis revealed findings consistent with refractory anemia with excess blasts; an initial karyotype revealed no clonal cytogenetic abnormalities. Four months after diagnosis, the patient developed transfusion-dependent thrombocytopenia. A repeat bone marrow biopsy showed equivalent pathology, but cytogenetic analysis demonstrated trisomy 8 in 4 of 20 cells karyotyped. The patient was started on a 12-week trial of paricalcitol, a vitamin D derivative. His treatment course was characterized by persistent moderate pancytopenia and hypercalcemia. Nine months after diagnosis, the patient was admitted to hospital with one week of headache, fever, and visual disturbance. Leukocytes were 28.67 x 103/μL with 11% segmented neutrophils and 70% band forms, Hgb 8.9 g/dl, and platelets 73 x 103/μL. Over the first 24 hours, the patient developed rapidly progressive proptosis leading to MRI of the skull that revealed an abnormal signal in the left frontal lobe. A CT 2 days later revealed extensive sinusitis with a left orbital mass. At resection, rhinocerebral mucormycosis involving the paranasal sinuses, orbit, and cerebral cortex was identified. We performed neutrophil function studies which showed two distinct populations; 59% showed normal oxidative burst capacity, but 41% showed impaired capacity. NBT test also sugested a broadened population of stimulated neutrophils. By light microscopy, numerous pale, agranular, Pelgeroid cells were visible. Despite extensive resection and systemic antibiotics, the patient expired on the 25th hospital day. This case illustrates that normal neutrophil number, in the setting of myelodysplasia, may not denote normal neutrophil function. Functional criteria of response should be considered in clinical studies of remittive therapy for myelodysplasia.