velocity in children and adolescents with sickle cell disease: association with hemolysis and hemoglobin oxygen desaturation. Haematologica, 2009, 94: 340–47
[40] Rother RP, Bell L, Hillmen P, et al. The clinical sequelae of intravascular
hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA, 2005, 293: 1653–62
[41] Repka T, Hebbel RP. Hydroxyl radical formation by sickle erythrocyte
membranes: role of pathologic iron deposits and cytoplasmic reducing agents. Blood, 1991, 78: 2753–58
[42] Reiter CD, Wang X, Tanus-Santos JE, et al. Cell-free hemoglobin limits
nitric oxide bioavailability in sickle-cell disease. Nat Med, 2002, 8: 1383–89
[43] Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells
synthesize nitric oxide from L-arginine. Nature, 1988, 333: 664–66[44] De Caterina R, Libby P, Peng HB, et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinfl ammatory cytokines. J Clin Invest, 1995, 96: 60–68
[45] Gladwin MT. Deconstructing endothelial dysfunction: soluble guanylyl
cyclase oxidation and the NO resistance syndrome. J Clin Invest, 2006, 116: 2330–32
[46] Morris CR, Kato GJ, Poljakovic M, et al. Dysregulated arginine
metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA, 2005, 294: 81–90
[47] Ataga KI, Moore CG, Hillery CA, et al. Coagulation activation and infl-
ammation in sickle cell disease-associated pulmonary hypertension. Haematologica, 2008, 93: 20–26
[48] Westerman M, Pizzey A, Hirschman J, et al. Microvesicles in haemo-globinopathies offer insights into mechanisms of hypercoagulability, haemolysis and the effects of therapy. Br J Haematol, 2008, 142: 126–35[49] Flint J, Harding RM, Boyce AJ, et al. The population genetics of the
haemoglobinopathies. Baillieres Clin Haematol, 1998, 11: 1–51
[50] Allison AC. Protection afforded by sickle cell trait against subtertian
malarial infection. BMJ, 1954, 1: 290–95
[51] Cavalli-Sforza LL, Menozzi P, Piazza A. The history and geography of
human genes. New Jersey, USA: Princeton University Press, 1994: 1088[52] Modell B, Darlison M. Global epidemiology of haemoglobin disorders
and derived service indicators. Bull World Health Organ, 2008, 86: 480–87
[53] Lysenko AJ, Semashko IN. Geography of malaria. A medico-geographic
profile of an ancient disease [in Russian]. In: Lebedew AW, ed. Itogi Nauki: Medicinskaja Geografija. Moscow, Russia: Academy of Science, 1968: 25–146
[54] Hay SI, Guerra CA, Tatem AJ, et al. The global distribution and
population at risk of malaria: past, present, and future. Lancet Infect Dis, 2004, 4: 327–36
[55] Williams TN, Mwangi TW, Wambua S, et al. Sickle cell trait and the risk
of Plasmodium falciparum malaria and other childhood diseases. J Infect Dis, 2005, 192: 178–86
[56] May J, Evans JA, Timmann C, et al. Hemoglobin variants and disease
manifestations in severe falciparum malaria. JAMA, 2007, 297: 2220–26[57] Wellems TE, Hayton K, Fairhurst RM. The impact of malaria parasitism:
from corpuscles to communities. J Clin Invest, 2009, 119: 2496–505[58] Serjeant GR. Mortality from sickle cell disease in Africa. BMJ, 2005,
330: 432–33
[59] Makani J, Williams TN, Marsh K. Sickle cell disease in Africa: burden
and research priorities. Ann Trop Med Parasitol, 2007, 101: 3–14
The Lancet Chinese Edition
专题研讨·Seminar
[60] Rahimy MC, Gangbo A, Ahouignan G, et al. Effect of a comprehensive
clinical care program on disease course in severely ill children with sickle cell anemia in a sub-Saharan African setting. Blood, 2003, 102: 834–38
[61] Williams TN, Uyoga S, Macharia A, et al. Bacteraemia in Kenyan
children with sickle-cell anaemia: a retrospective cohort and case-control study. Lancet, 2009, 374: 1364–70
[62] Adamkiewicz TV, Sarnaik S, Buchanan GR, et al. Invasive pneumococcal
infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal polysaccharide vaccination. J Pediatr, 2003, 143: 438–44
[63] Oniyangi O, Omari AA. Malaria chemoprophylaxis in sickle cell disease.
Cochrane Database Syst Rev, 2006, 4: CD003489
[64] Makani J, Komba AN, Cox SE, et al. Malaria in patients with sickle cell
anemia: burden, risk factors, and outcome at the outpatient clinic and during hospitalization. Blood, 2010, 115: 215–20
[65] McAuley CM, Webb C, Makani J, et al. High mortality from P.
falciparum in children living with sickle cell anemia on the coast of Kenya. Blood, 2010, 116: 1663–68
[66] Garenne M, Gakusi E. Health transitions in sub-Saharan Africa: overview
of mortality trends in children under 5 years old (1950–2000). Bull World Health Organ, 2006, 84: 470–78
[67] Bain BJ. Neonatal/newborn haemoglobinopathy screening in Europe and
Africa. J Clin Pathol, 2009, 62: 53–56
[68] Platt OS, Thorington BD, Brambilla DJ, et al. Pain in sickle cell disease.
Rates and risk factors. N Engl J Med, 1991, 325: 11–16
[69] Koshy M, Entsuah R, Koranda A, et al. Leg ulcers in patients with sickle
cell disease. Blood, 1989, 74: 1403–08
[70] Gilman JG, Huisman THJ. DNA sequence variation associated with
elevated fetal Gγ globin production. Blood, 1985, 66: 1463–65
[71] Thein SL, Menzel S, Peng X, et al. Intergenic variants of HBS1L-MYB
are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults. Proc Natl Acad Sci USA, 2007, 104: 11346–51
[72] Menzel S, Garner C, Gut I, et al. A QTL influencing Fcell production
maps to a gene encoding a zinc-finger protein on chromosome 2p15. Nat Genet, 2007, 39: 1197–99
[73] Lettre G, Sankaran VG, Bezerra MA, et al. DNA polymorphisms at
the BCL11A, HBS1L-MYB and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proc Natl Acad Sci USA, 2008, 105: 11869–74
[74] Higgs DR, Aldridge BE, Lamb J, et al. The interaction of alpha
thalassaemia and homozygous sickle-cell disease. N Engl J Med, 1982, 306: 1441–46
[75] Kar BC, Satapathy RK, Kulozik AE, et al. Sickle cell disease in Orissa
State, India. Lancet, 1986, 2: 1198–201
[76] Padmos MA, Roberts GT, Sackey K, et al. Two different forms of
homozygous sickle cell disease occur in Saudi Arabia. Br J Haematol, 1991, 79: 93–98
[77] Bernaudin F, Verlhac S, Chevret S, et al. G6PD deficiency, absence
of alpha-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia. Blood, 2009, 114: 742–43
[78] Vasavda N, Menzel S, Kondaveeti S, et al. The linear effects of
alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease. Br J Haematol, 2007, 138: 263–70[79] Nolan VG, Wyszynski DF, Farrer LA, et al. Hemolysis-associated
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