المؤلفون: Ataga, Kenneth I., Brittain, Julia E., Desai, Payal, May, Ryan, Jones, Susan, Delaney, John, Strayhorn, Dell, Hinderliter, Alan, Key, Nigel S.

المساهمون: Covas, Dimas Tadeu

المصدر: PLoS ONE ; volume 7, issue 1, page e29786 ; ISSN 1932-6203

الإتاحة: https://doi.org/10.1371/journal.pone.0029786Test

المؤلفون: Ataga, Kenneth I., Brittain, Julia E., Jones, Susan K., May, Ryan, Delaney, John, Strayhorn, Dell, Desai, Payal, Redding‐Lallinger, Rupa, Key, Nigel S., Orringer, Eugene P.

المصدر: British Journal of Haematology ; volume 152, issue 4, page 485-491 ; ISSN 0007-1048 1365-2141

الوصف: Summary The pathophysiology of pulmonary hypertension (PHT) in sickle cell disease (SCD) is probably multifactorial. Soluble fms‐like tyrosine kinase‐1 (sFLT‐1) is a member of the vascular endothelial growth factor receptor (VEGFR) family. By adhering to and inhibiting VEGF and placenta growth factor, it induces endothelial dysfunction. We sought to evaluate the association of sFLT‐1 with clinical complications of SCD. We confirmed that sFLT‐1 was significantly elevated in SCD patients compared to healthy, race‐matched control subjects. The level of sFLT‐1 was significantly higher in patients with PHT, but no association was observed between sFLT‐1 and the frequency of acute pain episodes or history of acute chest syndrome. sFLT‐1 was correlated with various measures of haemolysis, erythropoietin and soluble vascular cell adhesion molecule‐1. By inducing endothelial dysfunction, sFLT‐1 may contribute to the pathogenesis of SCD‐associated PHT, although this effect does not appear to be independent of haemolysis.

الإتاحة: https://doi.org/10.1111/j.1365-2141.2010.08410.xTest

المؤلفون: Ataga, Kenneth I., Moore, Charity G., Jones, Susan, Olajide, Oludamilola, Strayhorn, Dell, Hinderliter, Alan, Orringer, Eugene P.

المصدر: British Journal of Haematology ; volume 134, issue 1, page 109-115 ; ISSN 0007-1048 1365-2141

الوصف: Summary Although pulmonary hypertension (PHT) is a common complication in patients with sickle cell disease (SCD), the rate of development of PHT and the factors that affect disease progression are unknown. We observed 93 patients over a median follow‐up period of 2·6 years (range 0·2–5·1 years). Data were censored at the time of death or loss to follow‐up. Pulmonary hypertension was associated with an increased risk of death (relative risk, 9·24; 95% confidence interval: 1·2–73·3; P = 0·01). There was no difference in the risk of death when patients with different degrees of PHT were compared. Lactate dehydrogenase and blood urea nitrogen were significantly associated with PHT in a logistic regression model. Higher levels of fetal haemoglobin and treatment with hydroxycarbamide were observed more frequently in patients without PHT. Thirteen per cent of patients with no previous evidence of PHT developed PHT following 3 years of observation. In conclusion: (1) PHT, regardless of severity, is associated with an increased risk of death in SCD patients; (2) haemolysis is strongly associated with PHT in SCD; (3) high levels of fetal haemoglobin and hydroxycarbamide therapy may decrease the occurrence of PHT; (4) screening for PHT is indicated for SCD patients in their non‐crisis, steady states.

الإتاحة: https://doi.org/10.1111/j.1365-2141.2006.06110.xTest

المؤلفون: Desai, Payal C., May, Ryan C., Jones, Susan K., Strayhorn, Dell, Caughey, Melissa, Hinderliter, Alan, Ataga, Kenneth I.

المصدر: British Journal of Haematology, 162(6)

مصطلحات موضوعية: Cancerology, Antineoplastic agent, Cancérologie, Genetic disease, Echocardiography, Sonography, hydroxycarbamide, Antimetabolic, Follow up study, Velocity, Sickle cell anemia, Hemolytic anemia, progression, Hypertension artérielle pulmonaire, Cardiovascular disease, pulmonary hypertension, Hematology, Sickle cell disease, Hemopathy, Hématologie, Respiratory disease, Hemoglobinopathy, tricuspid regurgitant jet velocity

الوصف: Although echocardiography-derived tricuspid regurgitant jet velocity (TRV) is associated with increased mortality in sickle cell disease (SCD), its rate of increase and predictive markers of its progression are unknown. We evaluated 55 subjects (median age: 38 years, range: 20 – 65 years) with at least 2 measurable TRVs, followed for a median of 4.5 years (range: 1.0 – 10.5 years) in a single-centre, prospective study. Thirty-one subjects (56%) showed an increase in TRV, while 24 subjects (44%) showed no change or a decrease in TRV. A linear mixed effects model indicated an overall rate of increase in the TRV of 0.02 m/s per year (p = 0.023). The model showed that treatment with hydroxycarbamide was associated with an initial TRV that was 0.20 m/s lower than no such treatment (p = 0.033), while treatment with angiotensin converting enzyme inhibitors and inhibitors/ angiotensin receptor blockers was associated with an increase in the TRV (p = 0.006). In summary, although some patients have clinically meaningful increases, the overall rate of TRV increase is slow. Treatment with hydroxycarbamide may decrease the progression of TRV. Additional studies are required to determine the optimal frequency of screening echocardiography and the effect of therapeutic interventions on the progression of TRV in SCD.

العلاقة: https://doi.org/10.17615/wbeh-a020Test; https://cdr.lib.unc.edu/downloads/q237j000w?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/q237j000wTest

الإتاحة: https://doi.org/10.17615/wbeh-a020Test
https://cdr.lib.unc.edu/downloads/q237j000w?file=thumbnailTest
https://cdr.lib.unc.edu/downloads/q237j000wTest

المؤلفون: Ataga, Kenneth I., Strayhorn, Dell, Desai, Payal C., May, Ryan C., Jones, Susan K., Hinderliter, Alan, Caughey, Melissa

الوصف: Although echocardiography-derived tricuspid regurgitant jet velocity (TRV) is associated with increased mortality in sickle cell disease (SCD), its rate of increase and predictive markers of its progression are unknown. We evaluated 55 subjects (median age: 38 years, range: 20 – 65 years) with at least 2 measurable TRVs, followed for a median of 4.5 years (range: 1.0 – 10.5 years) in a single-centre, prospective study. Thirty-one subjects (56%) showed an increase in TRV, while 24 subjects (44%) showed no change or a decrease in TRV. A linear mixed effects model indicated an overall rate of increase in the TRV of 0.02 m/s per year (p = 0.023). The model showed that treatment with hydroxycarbamide was associated with an initial TRV that was 0.20 m/s lower than no such treatment (p = 0.033), while treatment with angiotensin converting enzyme inhibitors and inhibitors/ angiotensin receptor blockers was associated with an increase in the TRV (p = 0.006). In summary, although some patients have clinically meaningful increases, the overall rate of TRV increase is slow. Treatment with hydroxycarbamide may decrease the progression of TRV. Additional studies are required to determine the optimal frequency of screening echocardiography and the effect of therapeutic interventions on the progression of TRV in SCD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::e4fcddaaf7576d432293821226bfa055Test

المؤلفون: Ataga, Kenneth I., Brittain, Julia E., Moore, Dominic, Jones, Susan K., Hulkower, Ben, Strayhorn, Dell, Adam, Soheir, Redding-Lallinger, Rupa, Nachman, Patrick, Orringer, Eugene P.

المصدر: European Journal of Haematology, 85(3)

مصطلحات موضوعية: Albuminuria, Hypertension, Pulmonary, Cross-Sectional Studies, Young Adult, Humans, Adult, Age Distribution, FLT1 protein, human, Cohort Studies, Vascular Endothelial Growth Factor Receptor-1, Kidney Function Tests, Aging, Anemia, Sickle Cell, Hemolysis

الوصف: Pulmonary hypertension (PHT) is reported to be associated with measures of renal function in patients with sickle cell disease (SCD). The purpose of this exploratory study was to determine the relationship between albuminuria and both clinical and laboratory variables in SCD.

العلاقة: https://doi.org/10.17615/tk5s-3015Test; https://cdr.lib.unc.edu/downloads/kw52jf912?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/kw52jf912Test

الإتاحة: https://doi.org/10.17615/tk5s-3015Test
https://cdr.lib.unc.edu/downloads/kw52jf912?file=thumbnailTest
https://cdr.lib.unc.edu/downloads/kw52jf912Test

المؤلفون: Ataga, Kenneth I., Moore, Charity G., Hillery, Cheryl A., Jones, Susan, Whinna, Herbert C., Strayhorn, Dell, Sohier, Cathy, Hinderliter, Alan, Parise, Leslie V., Orringer, Eugene P.

المساهمون: School of Medicine, Department of Medicine, School of Medicine, Department of Pathology and Laboratory Medicine, UNC Medical Center, School of Medicine, Department of Biochemistry and Biophysics

المصدر: Haematologica, 93(1)

مصطلحات موضوعية: Hypertension artérielle pulmonaire, Respiratory disease, Hemopathy, Sickle cell anemia, Anémie à hématies falciformes, Hemoglobinopathy, Cellule endothéliale, Genetic disease, Cardiovascular disease, inflammation, Hemolytic anemia, Hematology, Endothelial cell, Pathologie de l'appareil respiratoire, Hématologie, Blood coagulation, pulmonary hypertension, endothelial activation, sickle cell disease, Coagulation sanguine, coagulation activation

الوصف: BACKGROUND: Pulmonary hypertension (PHT) is common in sickle cell disease (SCD). The purpose of this study was to determine whether markers of coagulation activation and inflammation are associated with PHT in SCD. DESIGN AND METHODS: This cross-sectional study was performed using a cohort of patients followed at an adult Sickle Cell Clinic. Pulmonary artery systolic pressure was determined by Doppler echocardiography, and the diagnosis of PHT was defined using age, sex and body mass index-adjusted reference ranges. Clinical laboratory examinations, including hematologic studies and biochemical tests, as well as various measures of coagulation activation, endothelial activation and inflammation, were conducted on SCD subjects and on healthy, race-matched control subjects without SCD. RESULTS: Patients with SCD (n=76) had higher plasma levels of markers of coagulation (thrombin-antithrombin complex, prothrombin fragment F1+2, D-dimer) and endothelial (soluble vascular endothelial cell adhesion molecule, sVCAM) activation compared with control subjects (n=6). SCD patients with PHT (n=26) had significantly higher levels of sVCAM compared with those patients without PHT (n=50). Although PHT patients showed increased plasma measures of coagulation activation, the differences were not statistically significant when compared to those of patients without PHT. HbSS patients with PHT also had a trend towards higher levels of other inflammatory cytokines (interleukins 6, 8 and 10) than HbSS patients without PHT. There was a modest negative correlation between hemoglobin and plasma measures of coagulation and endothelial activation, and modest positive correlations between markers of hemolysis and plasma measures of coagulation and endothelial activation. CONCLUSIONS: SCD patients with PHT have higher levels of markers of endothelial activation and other inflammatory markers than patients without PHT. A trend towards an increased level of markers of coagulation activation was observed in SCD patients with PHT compared with ...

العلاقة: https://doi.org/10.17615/73cj-cs83Test; https://cdr.lib.unc.edu/downloads/hd76s8022?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/hd76s8022Test

الإتاحة: https://doi.org/10.17615/73cj-cs83Test
https://cdr.lib.unc.edu/downloads/hd76s8022?file=thumbnailTest
https://cdr.lib.unc.edu/downloads/hd76s8022Test

المؤلفون: Moore, Dominic, Jones, Susan K., Orringer, Eugene P., Adam, Soheir, Hulkower, Ben, Brittain, Julia E., Nachman, Patrick, Ataga, Kenneth I., Redding-Lallinger, Rupa, Strayhorn, Dell

مصطلحات موضوعية: congenital, hereditary, and neonatal diseases and abnormalities, hemic and lymphatic diseases, urologic and male genital diseases

الوصف: Pulmonary hypertension (PHT) is reported to be associated with measures of renal function in patients with sickle cell disease (SCD). The purpose of this exploratory study was to determine the relationship between albuminuria and both clinical and laboratory variables in SCD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::294332c8eedec8af9bc28999635bdd77Test

المؤلفون: Ataga, Kenneth I, Sood, Namita, De Gent, Guy, Kelly, Eileen, Henderson, Ashley G, Jones, Susan, Strayhorn, Dell, Lail, Alice, Lieff, Susan, Orringer, Eugene P

المصدر: Department of Medicine

مصطلحات موضوعية: Adult, Anemia, Sickle Cell, Cross-Sectional Studies, Echocardiography, Doppler, Female, Hematologic Tests, Humans, Hypertension, Pulmonary, Logistic Models, Male, Prevalence, Respiratory Function Tests, Department of Medicine, Medicine and Health Sciences

الوصف: BACKGROUND: Recurrent vaso-occlusive episodes lead to progressive end-organ damage in patients with sickle cell disease. We sought to determine the prevalence of pulmonary hypertension in adult patients with sickle cell disease and to identify factors associated with this life-threatening complication. METHODS: Sixty patients (> or =18 years of age; mean [+/- SD] age, 37 +/- 13 years) followed at a University Medical Center were evaluated. They were selected by a systematic sampling of patients presenting to the clinic for routine follow-up visits. All enrolled subjects underwent a clinical examination, Doppler echocardiography, pulmonary function tests, and hematologic tests during a single visit. Pulmonary hypertension was defined using an age- and body mass index-adjusted nomogram. RESULTS: The prevalence of pulmonary hypertension was 30% (18/60). Ten patients had mild pulmonary hypertension (up to 44 mm Hg), 5 had moderate pulmonary hypertension (45 to 74 mm Hg), and 2 had severe pulmonary hypertension (> or =75 mm Hg). In a logistic regression model, both lower fetal hemoglobin level and lower systolic blood pressure were associated with the presence of pulmonary hypertension. CONCLUSION: We found that the prevalence of pulmonary hypertension in adult patients with sickle cell disease was substantial, particularly in those with lower levels of fetal hemoglobin and lower systolic blood pressure.

العلاقة: https://scholarlyworks.lvhn.org/medicine/4622Test; https://pubmed.ncbi.nlm.nih.gov/15501204Test/

الإتاحة: https://scholarlyworks.lvhn.org/medicine/4622Test
https://pubmed.ncbi.nlm.nih.gov/15501204Test/

المؤلفون: Ataga, Kenneth I., Sood, Namita, De Gent, Guy, Kelly, Eileen, Henderson, Ashley G., Jones, Susan, Strayhorn, Dell, Lail, Alice, Lieff, Susan, Orringer, Eugene P.

المصدر: The American Journal of Medicine ; volume 117, issue 9, page 665-669 ; ISSN 0002-9343

مصطلحات موضوعية: General Medicine

الإتاحة: https://doi.org/10.1016/j.amjmed.2004.03.034Test
https://api.elsevier.com/content/article/PII:S0002934304003845?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0002934304003845?httpAccept=text/plainTest