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Sickle Cell Anemia (sickle + cell_anemia)
Selected AbstractsFacial swelling and gingival enlargement in a patient with sickle cell diseaseORAL DISEASES, Issue 5 2001JE Scipio Sickle cell anemia is a frequent hemoglobinopathy in the Caribbean. While vaso-occlusion induced tissue injury in sickle cell anemia is common in various organs, orofacial lesions are rare. A 14-year-old Afro-Trinidadian boy suffering from sickle cell anemia developed an acute facial swelling, mimicking facial cellulitis of dental origin, which was caused by sickle cell-related hemorrhage. He also exhibited gingival enlargement, considered to be an outcome of repeated hemorrhagic episodes and fibrous repair. A new finding is the presence of erythrocyte-filled intraepithelial blood vessels in the gingival epithelium. We hypothesize this phenomena is a tissue response to hypoxia that occurs in sickle cell disease. [source] Clinical response of patients with sickle cell anemia to cromolyn sodium nasal sprayAMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2006Mehran Karimi Abstract Sickle cell anemia is the most common heritable hematological disease affecting humans. Although hydroxyurea is the most commonly used antisickling agent, several previous studies suggest that cromolyn sodium also prevents sickling when administered acutely. However, no previous studies have evaluated the safety or efficacy of prolonged administration of cromolyn to patients with sickle cell anemia. The purpose of this study, therefore, was to test the hypothesis that prolonged administration of cromolyn alone or in combination with hydroxyurea would decrease the incidence of pain crises and/or alter the chronic pain seen in patients with this disease. In this crossover, single-blind, in vivo and in vitro study, 17 patients with sickle cell disease were studied. Each patient had to fill out a standard pain chart. Every 3 months the patients' medications changed in the following manner: The first 3 months the patients used cromolyn sodium nasal spray; the second 3 months they received placebo nasal spray; the third 3 months they received cromolyn sodium nasal spray and hydroxyurea capsule; and the last 3 months they received hydroxyurea capsule and placebo nasal spray. The least pain was felt with the mixture of hydroxyurea capsule and cromolyn sodium nasal inhaler. Furthermore, with the other combinations of medications, there were no significant statistical changes in the number of sickled red blood cells. Every combination used in this survey had positive effects on decreasing the pain. cromolyn sodium nasal spray is significantly efficient in decreasing sickle cell crisis as well as pain intensity in patients with sickle cell anemia. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc. [source] Prenatal diagnosis of sickle syndromes in India: dilemmas in counsellingPRENATAL DIAGNOSIS, Issue 5 2005Roshan Colah Abstract Objectives The sickle gene is prevalent in the scheduled caste and tribal populations in India. The clinical presentation of sickle cell disease is extremely variable, and there are no neonatal screening programmes. This is the first report on prenatal diagnosis of sickle syndromes in 85 couples at risk (sickle cell anemia-69; sickle thalassemia-16) from different regions in India. Most of the couples were from a low socioeconomic group and their decisions were entirely dependent on the local counselling given. We have evaluated the acceptability of prenatal diagnosis and the dilemmas faced in counselling these families. Methods Chorion villus sampling was done in the first trimester and DNA analysis using reverse dot blot hybridization or restriction enzyme digestion with Dde1 in 65 cases. Cordocentesis was done in the second trimester and fetal blood analyses by automated HPLC in 20 cases who came late. Results 32.9% of couples came prospectively for diagnosis. 23.5% of fetuses were affected (sickle cell anemia-18, sickle thalassemia-2). The ,-thalassemia mutation in both cases was IVS 1,5(G- > C). All the couples with an unfavourable diagnosis opted for termination of pregnancy. Conclusion Sickle cell anemia has a relatively benign clinical course in some tribal groups in India. This raises a dilemma whether we are justified in advising prenatal diagnosis in all such cases. Copyright © 2005 John Wiley & Sons, Ltd. [source] Etiology of strokes in children with sickle cell anemiaDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 3 2006Michael R. DeBaun Abstract The most devastating complication of sickle cell anemia is cerebral infarction, affecting ,30% of all individuals with sickle cell anemia. Despite being one of the most common causes of stroke in infants and children, the mechanism of cerebral infarction in this population has not been extensively studied and is poorly understood. Multiple, synergistic factors are important in the pathogenesis of stroke including the hemodynamic effects of cerebral arterial occlusive disease, viscosity, chronic and acute anemia and acute medical events. This review focuses on the relationship between these factors in order to provide a foundation for further study of the etiology of strokes in this high-risk population. MRDD Research Reviews 2006;12:192,199. © 2006 Wiley-Liss, Inc. [source] Emergency Nurses' Utilization of Ultrasound Guidance for Placement of Peripheral Intravenous Lines in Difficult-access PatientsACADEMIC EMERGENCY MEDICINE, Issue 12 2004Larry Brannam MD Objectives: Emergency nurses (ENs) typically place peripheral intravenous (IV) lines, but if repeated attempts fail, emergency physicians have to obtain peripheral or central access. The authors describe the patient population for which ultrasound (US)-guided peripheral IVs are used and evaluate the success rates for such lines by ENs. Methods: This was a prospective observational study of ENs in a Level I trauma center with a census of 75,000, performing US-guided IV line placement on difficult-to-stick patients (repeated blind IV placement failure or established history). ENs were trained on an inanimate model after a 45-minute lecture. Surveys were filled out after each US-guided IV attempt on a patient. ENs could decline to fill out surveys, which recorded the reason for use of US, type of patient, and success. Successful cannulation was confirmed by drawing blood and flushing fluids. Descriptive statistics were used to evaluated data. Results: A total of 321 surveys were collected in a five-month period no ENs declined to participate. There were 280 (87%) successful attempts. Twelve (29%) of the 41 failure patients required central lines, 9 (22%) received external jugular IVs, and 20 (49%) had peripheral IV access placed under US guidance by another nurse or physician. Twenty-eight percent (90) of all patients were obese, 18% (57) had sickle cell anemia, 10% (31) were renal dialysis patients, 12% (40) were IV drug abusers, and 19% (61) had unspecified chronic illness. The remainder had no reason for difficult access given. There were four arterial punctures. Conclusions: ENs had a high success rate and few complications with use of US guidance for vascular access in a variety of difficult-access patients. [source] Human platelet alloantigens (HPA) 1, HPA2, HPA3, HPA4, and HPA5 polymorphisms in sickle cell anemia patients with vaso-occlusive crisisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2009Abeer M. Al-Subaie Abstract Objectives:, Vaso-occlusive crisis (VOC) is a significant cause of morbidity and mortality in sickle cell anemia (SCA) patients. Insofar as polymorphism in human platelet alloantigen (HPA) exhibit a prothrombotic nature, we hypothesized that specific HPA polymorphic variants are associated with VOC. We investigated the distribution of HPA1, HPA2, HPA3, HPA4, and HPA5 alleles genotypes among VOC and non-VOC control SCA patients. Patients/methods:, This was a case,control study. Study subjects comprised SCA patients with (VOC group; n = 127) or without (Steady-state group; n = 130) VOC events. HPA genotyping was done by PCR-SSP. Results:, Significantly higher frequencies of HPA-2b, HPA-3b, and HPA-5b alleles, and marked enrichment of HPA-3b/3b, HPA-5a/5b, and HPA-5b/5b genotypes, were seen in VOC than in control SCA patients. Taking homozygous wild-type genotypes as reference, univariate analysis identified HPA-3a/3b, HPA-3b/3b, and HPA-5b/5b to be associated with VOC. Multivariate analysis confirmed the independent association of only HPA-3a/3b and HPA-3b/3b genotypes with VOC. HPA-3 genotypes were significantly correlated with VOC frequency, type, and medication, and requirement for hospitalization. While both HPA 3a/3b (P = 0.002; OR = 2.94; 95% CI = 1.49,5.77) and 3b/3b (P = 0.006; OR = 3.16; 95% CI = 1.40,7.17) genotypes were associated with need for hospitalization, only HPA-3b/3b was associated with VOC frequency, type (localized vs. generalized), and medication (narcotics vs. NSAIDs). Conclusion:, This confirms the association of HPA polymorphisms with SCA VOC, of which HPA-3 appears to be independent genetic risk factors for SCA VOC. [source] Epidemiologic Analysis of an Urban, Public Emergency Department's Frequent UsersACADEMIC EMERGENCY MEDICINE, Issue 6 2000Joshua H. Mandelberg BA Abstract. Objectives: To determine how the demographic, clinical, and utilization characteristics of emergency department (ED) frequent users differ from those of other ED patients. Methods: A cross-sectional and retrospective cohort study was performed using a database of all 348,858 visits to the San Francisco General Hospital ED during a five-year period (July 1, 1993, to June 30, 1998). A "frequent user" visited the ED five or more times in a 12-month period. Results: Frequent users constituted 3.9% of ED patients but accounted for 20.5% of ED visits. The relative risk (RR) of frequent use was high among patients who were homeless (RR = 4.5), African American (RR = 1.8), and Medi-Cal sponsored (RR = 2.1). Frequent users were more likely to be seen for alcohol withdrawal (RR = 4.4), alcohol dependence (RR = 3.4), and alcohol intoxication (RR = 2.4). Frequent users were also more likely to visit for exacerbations of chronic conditions, including sickle cell anemia (RR = 8.0), renal failure (RR = 3.6), and chronic obstructive pulmonary disease (RR = 3.3). They were less likely to visit for all forms of trauma (RR = 0.43). Survival analysis showed that only 38% of frequent users for one year remained frequent users the next year. However, 56% of frequent users for two consecutive years remained frequent users in the third year. Conclusions: Frequent use of the ED reflects the urban social problems of homelessness, poverty, alcohol abuse, and chronic illness. Frequent use of the ED shows a high rate of decline from one year to the next. This rate of decline slows after the first year and suggests the existence of a smaller group of chronic frequent users. [source] A primary care provider's guide to preventive and acute care management of adults and children with sickle cell diseaseJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 5 2009Ardie Pack-Mabien RNC, CRNP (Clinical Nurse Practitioner & Nurse Manager) Abstract Purpose: To familiarize primary care providers (PCPs) with the pathophysiological processes, diagnostic evaluation, and medical management of sickle hemoglobinopathies and their complications. Current standards of care, clinical research advances, and new treatment options will also be addressed to assist PCPs in the management of sickle cell disease (SCD). Data sources: A selective search and review of the current literature on SCD and the authors' experience. Conclusions: Management of individuals with SCD is very complex, requiring a multidisciplinary approach that includes the patient or parent, PCP, specialist, nurse, and social worker. More patients living with SCD are relying on PCPs in nonspecialty practices for comprehensive disease management. Implications for practice: Newborn screening detects new cases of SCD annually. The median life expectancy has more than doubled for individuals with sickle cell anemia. Healthcare providers are now in an era of increased routine screening, assessment, and management of chronic complications from this illness not previously seen in the care of adults with SCD. [source] Facial swelling and gingival enlargement in a patient with sickle cell diseaseORAL DISEASES, Issue 5 2001JE Scipio Sickle cell anemia is a frequent hemoglobinopathy in the Caribbean. While vaso-occlusion induced tissue injury in sickle cell anemia is common in various organs, orofacial lesions are rare. A 14-year-old Afro-Trinidadian boy suffering from sickle cell anemia developed an acute facial swelling, mimicking facial cellulitis of dental origin, which was caused by sickle cell-related hemorrhage. He also exhibited gingival enlargement, considered to be an outcome of repeated hemorrhagic episodes and fibrous repair. A new finding is the presence of erythrocyte-filled intraepithelial blood vessels in the gingival epithelium. We hypothesize this phenomena is a tissue response to hypoxia that occurs in sickle cell disease. [source] Utilization of analgesics in the multicenter study of hydroxyurea in sickle cell anemia: Effect of sex, age, and geographical location,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2010Samir K. Ballas First page of article [source] The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up,,§¶,,,,,§§AMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2010Martin H. Steinberg A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at , = 0.05 level (P -value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source] Pseudo-Gaucher cells in sickle cell anemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2010Barbara J. Bain No abstract is available for this article. [source] Letter in response to: "Pulmonary thrombi are not detected by 3D magnetic resonance angiography in adults with sickle cell anemia and an elevated triscuspid regurgitant jet velocity",AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2010Eduard J. Van Beers No abstract is available for this article. [source] Author response letter to: "Pulmonary thrombi are not detected by 3D magnetic resonance angiography in adults with sickle cell anemia and an elevated tricuspid regurgitant jet velocity" ,AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2010Joshua J. Field No abstract is available for this article. [source] Resolution of cerebral artery stenosis in a child with sickle cell anemia treated with hydroxyurea,AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2010Rachael F. Grace No abstract is available for this article. [source] Proinflammatory phenotype with imbalance of KLF2 and RelA: Risk of childhood stroke with sickle cell anemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Judy Enenstein Altered inflammation signaling within the cerebral vasculature may be an important risk factor for stroke in children with sickle cell anemia (SCA). This study examines how differential expression of NF,B/p65 (RelA), KLF2, and other transcription factors may act as switches in inflammation signaling leading to observed differences between non-SCA (NS) African Americans and African Americans with SCA who are either at risk (AR) or not at risk (NAR) of childhood stroke based on occurrence of Circle of Willis disease. Clover/Transfac analysis was used to identify overrepresented transcription factor binding motifs on genes associated with inflammation. Transcription factor binding motifs for the NF,B family and RFX1 were overrepresented on inflammation signaling gene set analysis. Variations in protein expression were determined by flow cytometry of blood outgrowth endothelial cells (BOECs) from NS, AR, and NAR donors and Western blots of protein extracts from both unstimulated and TNF,/IL1,-stimulated BOECs. BOECs from patients with SCA had more cytoplasmic-derived RelA compared with NS BOECs. Sickle BOECs also had heightened responses to inflammatory stimuli compared with NS BOECs, as shown by increased nuclear RelA, and intracellular adhesion molecule (ICAM) response to TNF,/IL1, stimulation. Multiple control points in RelA signaling were associated with risk of childhood stroke. The ratio of proinflammatory factor RelA to anti-inflammatory factor KLF2 was greater in BOECs from AR donors than NS donors. Group risk of childhood stroke with SCA was greatest among individuals who exhibited increased expression of proinflammatory transcription factors and decreased expression of transcription factors that suppress inflammation. Am. J. Hematol. 2010. © 2009 Wiley-Liss, Inc. [source] Genetic modifiers of the severity of sickle cell anemia identified through a genome-wide association study,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Paola Sebastiani We conducted a genome-wide association study (GWAS) to discover single nucleotide polymorphisms (SNPs) associated with the severity of sickle cell anemia in 1,265 patients with either "severe" or "mild" disease based on a network model of disease severity. We analyzed data using single SNP analysis and a novel SNP set enrichment analysis (SSEA) developed to discover clusters of associated SNPs. Single SNP analysis discovered 40 SNPs that were strongly associated with sickle cell severity (odds for association >1,000); of the 32 that we could analyze in an independent set of 163 patients, five replicated, eight showed consistent effects although failed to reach statistical significance, whereas 19 did not show any convincing association. Among the replicated associations are SNPs in KCNK6 a K+ channel gene. SSEA identified 27 genes with a strong enrichment of significant SNPs (P < 10,6); 20 were replicated with varying degrees of confidence. Among the novel findings identified by SSEA is the telomere length regulator gene TNKS. These studies are the first to use GWAS to understand the genetic diversity that accounts the phenotypic heterogeneity sickle cell anemia as estimated by an integrated model of severity. Additional validation, resequencing, and functional studies to understand the biology and reveal mechanisms by which candidate genes might have their effects are the future goals of this work. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] Endothelial nitric oxide synthase and nitric oxide regulate endothelial tissue factor expression in vivo in the sickle transgenic mouse,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Anna Solovey Activation of the coagulation system is a characteristic feature of sickle cell anemia, which also includes clinical thrombosis. The sickle transgenic mouse abnormally expresses tissue factor (TF) on the pulmonary vein endothelium. Knowing that this aberrancy is stimulated by inflammation, we sought to determine whether nitric oxide (NO) contributes to regulation of endothelial TF expression in the sickle mouse model. We used the NY1DD sickle mouse, which exhibits a low-TF to high-TF phenotype switch on exposure to hypoxia/reoxygenation. Manipulations of NO biology, such as breathing NO or addition of arginine or L -NAME (N -nitro- L -arginine-methyl-ester) to the diet, caused significant modulations of TF expression. This was also seen in hBERK1 sickle mice, which have a different genetic background and already have high-TF even at ambient air. Study of NY1DD animals bred to overexpress endothelial nitric oxide synthase (eNOS; eNOS-Tg) or to have an eNOS knockout state (one eNOS,/, animal and several eNOS+/, animals) demonstrated that eNOS modulates endothelial TF expression in vivo by down-regulating it. Thus, the biodeficiency of NO characteristic of patients with sickle cell anemia may heighten risk for activation of the coagulation system. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] Rituximab as an effective treatment of hyperhemolysis syndrome in sickle cell anemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Claude Bachmeyer No abstract is available for this article. [source] Pulmonary thrombi are not detected by 3D magnetic resonance angiography in adults with sickle cell anemia and an elevated triscuspid regurgitant jet velocity,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2009Joshua J. Field No abstract is available for this article. [source] Growth patterns in children with sickle cell anemia during pubertyPEDIATRIC BLOOD & CANCER, Issue 4 2009Melissa Rhodes MD Abstract Background Previous studies of children with homozygous sickle cell anemia (SCA) show impaired growth and maturation. The correlation of this suboptimal growth with metabolic and hematological factors during puberty is poorly understood. Procedure We studied a group of pre-adolescent children with SCA (19 males, 14 females) and healthy controls (16 males, 15 females) matched for race, sex, body size, and pubertal development. Height, weight, body mass index (BMI), and body composition changes were longitudinally assessed over a 2-year period and compared between the groups and with Z scores based on US growth charts. These changes were correlated with hemoglobin (Hgb) concentration and with energy expenditure (EE) measured using indirect whole-room calorimetry. Results Children with SCA progressed through puberty slower than control children. While, after 2 years, pubertal males with SCA were shorter, their annual increases in weight were not different from controls. The mean fat free mass (FFM) increments were significantly less in males and females with SCA than in control children. In males with SCA, growth in height declined over time and was significantly slower than in matched controls (P,<,0.05). Conclusion Growth delays were present during puberty in children with SCA. Decreased growth velocity in children with SCA was independently associated with decreased Hgb concentration and increased total EE. Pediatr Blood Cancer 2009;53:635,641. © 2009 Wiley-Liss, Inc. [source] Arterial spin-labeled perfusion combined with segmentation techniques to evaluate cerebral blood flow in white and gray matter of children with sickle cell anemia,PEDIATRIC BLOOD & CANCER, Issue 1 2009Kathleen J. Helton MD Abstract Background Changes in cerebral perfusion are an important feature of the pathophysiology of sickle cell anemia (SCA); cerebrovascular ischemia occurs frequently and leads to neurocognitive deficits, silent infarcts, and overt stroke. Non-invasive MRI methods to measure cerebral blood flow (CBF) by arterial spin labeling (ASL) afford new opportunities to characterize disease- and therapy-induced changes in cerebral hemodynamics in patients with SCA. Recent studies have documented elevated gray matter (GM) CBF in untreated children with SCA, but no measurements of white matter (WM) CBF have been reported. Procedures Pulsed ASL with automated brain image segmentation-classification techniques were used to determine the CBF in GM, WM, and abnormal white matter (ABWM) of 21 children with SCA, 18 of whom were receiving hydroxyurea therapy. Results GM and WM CBF were highly associated (R2,=,0.76, P,<,0.0001) and the GM to WM CBF ratio was 1.6 (95% confidence interval: 1.43,1.83). Global GM CBF in our treated cohort was 87,±,24 mL/min/100 g, a value lower than previously reported in untreated patients with SCA. CBF was elevated in normal appearing WM (43,±,14 mL/min/100 g) but decreased in ABWM (6,±,12 mL/min/100 g), compared to published normal pediatric controls. Hemispheric asymmetry in CBF was noted in most patients. Conclusions These perfusion measurements suggest that hydroxyurea may normalize GM CBF in children with SCA, but altered perfusion in WM may persist. This novel combined approach for CBF quantification will facilitate prospective studies of cerebral vasculopathy in SCA, particularly regarding the effects of treatments such as hydroxyurea. Pediatr Blood Cancer 2009;52:85,91. © 2008 Wiley-Liss, Inc. [source] Liver biopsy results in patients with sickle cell disease on chronic transfusions: Poor correlation with ferritin levelsPEDIATRIC BLOOD & CANCER, Issue 1 2008Lina B. Karam MD Abstract Background: Chronic transfusions are effective in preventing stroke and other complications of sickle cell disease. The aim of this study was to determine whether serum ferritin levels correlated with liver iron content in sickle cell patients on chronic transfusion. Procedure: Forty-four liver biopsy specimens from 38 patients with homozygous sickle cell anemia (HbSS) and one patient with sickle thalassemia receiving chronic transfusions were studied. Five patients underwent a second liver biopsy for follow up. Three ferritin measurements were used to calculate a mean for each patient. The association between serum ferritin levels and liver iron quantitation was measured using the Spearman rank correlation, and sensitivity and specificity were determined for selected threshold values of serum ferritin. Results: Serum ferritin levels ranged from 515 to 6076 ng/ml, liver iron concentration ranged from 1.8 to 67.97 mg/g dry weight. The amount of iron per gram liver dry weight was moderately correlated with serum ferritin values (r,=,0.46). The correlation of duration of transfusion with serum ferritin (r,=,0.40) and with liver iron content (r,=,0.41) also indicated moderate correlation. Liver biopsy results led to changes in the management after 29/44 (66%) of the biopsies. Serum ferritin ,2500 ng/ml predicted high liver iron content (,7 mg/g), with a sensitivity of 62.5% and a specificity of 77.8%. Conclusion: We found a poor correlation between serum ferritin levels and liver iron content (LIC). Despite being on chelation therapy, many patients on chronic transfusion had high levels of liver iron. Measurement of LIC is highly recommended in these patients. Pediatr Blood Cancer 2008;50:62,65. © 2007 Wiley-Liss, Inc. [source] Urinary hepcidin in congenital chronic anemiasPEDIATRIC BLOOD & CANCER, Issue 1 2007Susan L. Kearney MD Abstract Background Hepcidin, a regulator for iron homeostasis, is induced by inflammation and iron burden and suppressed by anemia and hypoxia. This study was conducted to determine the hepcidin levels in patients with congenital chronic anemias. Procedure Forty-nine subjects with anemia, varying degrees of erythropoiesis and iron burden were recruited. Eight children with immune thrombocytopenia were included as approximate age-matched controls. Routine hematologic labs and urinary hepcidin (uhepcidin) levels were assessed. For thalassemia major (TM) patients, uhepcidin was obtained pre- and post-transfusion. Results In TM, uhepcidin levels increased significantly after transfusion, demonstrated wide variance, and the median did not significantly differ from controls or thalassemia intermedia (TI). In both thalassemia syndromes, the hepcidin to ferritin ratio, a marker of the appropriateness of hepcidin expression relative to the degree of iron burden, was low compared to controls. In TI and sickle cell anemia (SCA), median uhepcidin was low compared to controls, P,=,0.013 and <0.001, respectively. In thalassemia subjects, uhepcidin levels were positively associated with ferritin. In subjects with SCA, uhepcidin demonstrated a negative correlation with reticulocyte count. Conclusions This study examines hepcidin levels in congenital anemias. In SCA, hepcidin was suppressed and inversely associated with erythropoietic drive. In thalassemic syndromes, hepcidin was suppressed relative to the degree of iron burden. Transfusion led to increased uhepcidin. In thalassemia, the relative influence of known hepcidin modifiers was more difficult to assess. In thalassemic syndromes where iron overload and anemia have opposing effects, the increased erythropoietic drive may positively influence hepcidin production. Pediatr Blood Cancer 2007;48:57,63. © 2005 Wiley-Liss, Inc. [source] Hydroxyurea treatment in children with sickle cell anemia in Central America and the Caribbean countriesPEDIATRIC BLOOD & CANCER, Issue 1 2006Eva Svarch MD No abstract is available for this article. [source] Genome-wide association studies and the genetic dissection of complex traits,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Paola Sebastiani The availability of affordable high throughput technology for parallel genotyping has opened the field of genetics to genome-wide association studies (GWAS), and in the last few years hundreds of articles reporting results of GWAS for a variety of heritable traits have been published. What do these results tell us? Although GWAS have discovered a few hundred reproducible associations, this number is underwhelming in relation to the huge amount of data produced, and challenges the conjecture that common variants may be the genetic causes of common diseases. We argue that the massive amount of genetic data that result from these studies remains largely unexplored and unexploited because of the challenge of mining and modeling enormous data sets, the difficulty of using nontraditional computational techniques and the focus of accepted statistical analyses on controlling the false positive rate rather than limiting the false negative rate. In this article, we will review the common approach to analysis of GWAS data and then discuss options to learn more from these data. We will use examples from our ongoing studies of sickle cell anemia and also GWAS in multigenic traits. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Microarray analysis of liver gene expression in iron overloaded patients with sickle cell anemia and beta-thalassemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2009Jonathan M. Flanagan Chronic transfusion therapy is used clinically to supply healthy erythrocytes for patients with sickle cell anemia (SCA) or beta-thalassemia major (TM). Despite the benefits of red blood cell transfusions, chronic transfusions lead to iron accumulation in key tissues such as the heart, liver, and endocrine glands. Transfusion-acquired iron overload is recognized as a cause of morbidity and mortality among patients receiving chronic transfusions. At present, there is little understanding of molecular events that occur during transfusional iron loading and the reasons for the large inter-individual variation observed clinically in transfusion-acquired iron accumulation. To address these issues, we examined whether any liver-expressed genes in SCA or TM patients with transfusional iron overload were associated with the degree of iron accumulation. Specifically, we performed microarray analysis on liver biopsy specimens comparing SCA patients with mild or severe iron overload and also compared SCA with TM patients. Fifteen candidate genes were identified with significantly differential expression between the high and low liver iron concentrations. SCA patients and 20 candidate genes were detected between the SCA and TM patient comparison. Subsequent quantitative PCR experiments validated 12 candidate genes; with GSTM1, eIF5a, SULF2, NTS, and HO-1 being particularly good prospects as genes that might affect the degree of iron accumulation. Future work will determine the baseline expression of these genes prior to transfusional iron overload and elucidate the full impact of these genes on the inter-individual variation observed clinically in transfusion-acquired iron accumulation. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Growth of lung function in children with sickle cell anemiaPEDIATRIC PULMONOLOGY, Issue 11 2008Joshua J. Field MD Abstract Lung disease is a common cause of morbidity among children with sickle cell disease (SCD). Although cross-sectional studies of children with SCD describe abnormal pulmonary function, the pattern of lung function growth in these children compared to children in the general population is not known. To provide preliminary evidence that growth of lung function is attenuated in children with SCD, we conducted a retrospective cohort study of children with hemoglobin SS (HbSS) ages 6,19 years who received at least two spirometry assessments for clinical care. The growth of lung function in these cases was compared to age, gender, and race-specific children without SCD or respiratory complaints from the Harvard Six Cities Study (H6CS). Seventy-nine children with HbSS contributed 363 spirometry measurements (mean per child,=,4.6, median,=,4.0, range,=,2,17) and 255 controls contributed 1,543 spirometry measurements (mean per child,=,6.1, median,=,6.0, range,=,2,13). Longitudinal forced expiratory volume in 1 sec (FEV1) was lower for boys and girls with HbSS compared to children in the general population, P,=,0.031 and P,=,0.002, respectively. When compared to the H6CS cohort, girls with HbSS showed lower longitudinal forced vital capacity (FVC) (P,<,0.001) and FEV1/FVC (0.038); there was no difference in FVC or FEV1/FVC between boys in the HbSS and H6CS cohort. We conclude that growth of lung function is reduced in children with HbSS compared to children in the general population. Gender may influence the risk of developing abnormal lung function and airway obstruction in children with HbSS. Pediatr Pulmonol. 2008; 43:1061,1066. © 2008 Wiley-Liss, Inc. [source] Airway hyperresponsiveness and acute chest syndrome in children with sickle cell anemiaPEDIATRIC PULMONOLOGY, Issue 3 2007Karl P. Sylvester PhD Abstract To determine the occurrence and magnitude of airway hyperresponsiveness (AHR) in children with sickle cell anemia (SCA) who had or had not had acute chest syndrome (ACS) episodes. A subsidiary aim was to determine whether cold air and exercise challenge testing gave similar results in children with SCA. AHR would be greater in SCA children who had had an ACS episode compared to those who had not. Prospective observational study. Forty-two SCA children (median age of 11.5 [range 6.1,16.8] years); 12 children had been previously hospitalized for an ACS episode. AHR was assessed by the change in forced expiratory volume in 1 sec (FEV1) to a cold air challenge and in a subset of the children to an exercise challenge. A positive result to either challenge was deemed to have occurred if the FEV1 fell by at least 10% from the pre-challenge baseline. The magnitude of change in FEV1 following the cold air challenge was similar in children who had or had not had an ACS episode. Six children had a positive response to the cold air challenge (AHR); none had had an ACS hospitalization. Similar proportions of children responded to the cold air and exercise challenge and the magnitude of response to the two tests was similar. Some children, however, responded only to a cold air challenge and others only to an exercise challenge. SCA children who had had an ACS hospitalization episode compared to those who had not were not more likely to respond to a cold air challenge. Importantly, if AHR is to be correctly diagnosed, some SCA children will require to undergo both cold air and exercise challenge testing. Pediatr Pulmonol. 2007; 42:272,276. © 2007 Wiley-Liss, Inc. [source] Usefulness and limitations of Bayesian network model as a mortality risk assessment tool in sickle cell anemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009Parameswaran Anoop No abstract is available for this article. [source] | |||||||||||||