Hemoglobina A1c, diabetes mellitus, nefropatía diabética y enfermedad renal crónica
Resumen
La diabetes mellitus (DBT), la nefropatía diabética (ND) y la enfermedad renal crónica (ERC) son enfermedades prevalentes en nuestra región, Sudamérica. Los niveles de hemoglobina A1c (HbA1c) han sido relacionados al desarrollo y a la evolución de la ND. Hace dos décadas había gran variabilidad en los resultados, Los países líderes en investigación científica organizaron programas de estandarización de la HbA1c, logrando mejorar la calidad y la confiabilidad de los resultados. Los objetivos de este trabajo fueron describir el problema DBT, ND y ERC en Sudamérica y en su contexto analizar metodológicamente la HbA1c. Para esto, revisamos el impacto de estas enfermedades en nuestra región, contemplando aspectos básicos de la HbA1c y algunas situaciones que producen interferencias como la carbamilación de la hemoglobina, modificación post-traduccional asociada a la uremia. También nos enfocamos en técnicas estadísticas universalmente utilizadas para la evaluación de ensayos como: linealidad, concordancia y precisión. Adicionalmente, incluimos un análisis de los métodos disponibles y de los precios de cada determinación de HbA1c en diez países de Sudamérica.
Para prevenir, diagnosticar y tratar la DBT, la ND y la ERC es indispensable contar con herramientas de última generación, disponibles para todas las personas. En nuestra región el acceso a ensayos, equipos y laboratorios enmarcados en programas de estandarización de la HbA1c, internacionalmente aceptados, es una tarea pendiente. Millones de individuos de las generaciones presentes y futuras de Sudamérica padecerán DBT, ND y ERC, necesitamos llevar la voz de la ciencia a esas personas con el “hacer” cotidiano.
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NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 2016;387(10027):1513-30.
Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103(2):137-49.
Atlas de la Diabetes de la FID: región Sudamérica y América Central [Internet]. 5ª ed. Bruselas: International Diabetes Federation, 2015. Disponible en: http://www.diabetesatlas.org/resources/2015-atlas.html [Consulta: 02/10/2017].
GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study. Lancet 2017;390(10100): 1211-59.
Carranza K, Veron D, Cercado A, Bautista N, Pozo W, Tufro A, et al. Cellular and molecular aspects of diabetic nephropathy; the role of VEGF-A. Nefrologia 2015;35(2):131-38.
Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, Goldstein-Fuchs J, et al. Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care. 2014;37(10):2864-83.
Gallagher H, Suckling RJ. Diabetic nephropathy - where are we on the journey from pathophysiology to treatment? Diabetes Obes Metab. 2016;18(7):641-7.
Eggers PW. Has the incidence of end-stage renal disease in the USA and other countries stabilized? Curr Opin Nephrol Hypertens. 2011;20(3):241-5.
Lugon JR, Strogoff de Matos JP. Disparities in end-stage renal disease care in South America. Clin Nephrol. 2010;74(Suppl 1):S66-71.
Rosa-Diez G, González-Bedat M, Pecoits-Filho R, Marinovich S, Fernández S, Lugon J, et al. Renal replacement therapy in Latin American end-stage renal disease. Clin Kidney J. 2014;7(4):431-6.
World Kidney Day 2017, Kidney disease and obesity [Internet]. International Society of Nephrology, Global Operations Center. Disponible en: http://www.worldkidneyday.org/ [Consulta: oct. 2017].
Cusumano AM, Rosa-Diez GJ, Gonzalez-Bedat MC. Latin American Dialysis and Transplant Registry: Experience and contributions to end-stage renal disease epidemiology. World J Nephrol. 2016;5(5):389-97.
Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. Chronic kidney disease: global dimension and perspectives. Lancet 2013;382(9888):260-72.
Couser WG, Remuzzi G, Mendis S, Tonelli M. The contribution of chronic kidney disease to the global burden of major noncommunicable diseases. Kidney Int. 2011;80(12):1258-70.
Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Eckardt KU, et al. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes. Kidney Int. 2007;72(3):247-59.
Brück K, Stel VS, Gambaro G, Hallan S, Völzke H, Ärnlöv J, et al. CKD prevalence varies across the european general population. J Am Soc Nephrol. 2016;27(7):2135-47.
Estados Unidos. National Kidney Foundation. Global facts: about kidney disease [Internet]. Disponible en: https://www.kidney.org/kidneydisease/global-facts-about-kidney-disease [Consulta: oct. 2017].
Gallagher H, Methven S, Casula A, Thomas N, Tomson CR, Caskey FJ, et al. A programme to spread eGFR graph surveillance for the early identification, support and treatment of people with progressive chronic kidney disease (ASSIST-CKD): protocol for the stepped wedge implementation and evaluation of an intervention to reduce late presentation for renal replacement therapy. BMC Nephrol. 2017;18(1):131.
Klessens CQ, Woutman TD, Veraar KA, Zandbergen M, Valk EJ, Rotmans JI, et al. An autopsy study suggests that diabetic nephropathy is underdiagnosed. Kidney Int. 2016;90(1):149-56.
Shimizu M, Furuichi K, Toyama T, Kitajima S, Hara A, Kitagawa K, et al. Long-term outcomes of Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy. Diabetes Care. 2013;36(11):3655-62
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131): 837-53.
Diabetes Control and Complications Trial Research Group, Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-86.
ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, Neal B, Billot L, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560-72.
Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32(1):193-203.
Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129-39.
Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010;376(9739):419-30.
Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321(7258):405-12.
Bangstad HJ, Osterby R, Dahl-Jørgensen K, Berg KJ, Hartmann A, Hanssen KF. Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy. Diabetologia 1994;37(5):483-90.
Fioretto P, Mauer SM, Bilous RW, Goetz FC, Sutherland DE, Steffes MW. Effects of pancreas transplantation on glomerular structure in insulin-dependent diabetic patients with their own kidneys. Lancet. 1993;342(8881):1193-6.
Haraguchi K, Hara S, Ubara Y, Tanaka S, Nukui I, Shimura H, et al. Complete remission of diabetic nephropathy in a type 1 diabetic patient with near-nephrotic range proteinuria and reduced renal function. Diabetes Res Clin Pract. 2009;83(3):295-9.
Iaconelli A, Panunzi S, De Gaetano A, Manco M, Guidone C, Leccesi L, et al. Effects of bilio-pancreatic diversion on diabetic complications: a 10-year follow-up. Diabetes Care. 2011;34(3):561-7.
Inzucchi SE, Zinman B, Wanner C, Ferrari R, Fitchett D, Hantel S, et al. SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res. 2015;12(2):90-100.
Wanner C, Inzucchi SE, Lachin JM, Fitchett D, Von Eynatten M, Mattheus M, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(18):323-34.
International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32(7):1327-34.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2012;35(Suppl 1): S64-71.
WHO Guidelines Approved by the Guidelines Review Committee. Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus: Abbreviated Report of a WHO Consultation [Internet]. Geneva: World Health Organization, 2011. Disponible en: https://www.ncbi.nlm.nih.gov/books/NBK304267/ [Consulta: oct. 2017].
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(Suppl 1):S81-90.
American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2016;39 (Suppl 1):S13-22.
Weykamp C, John WG, Mosca A. A review of the challenge in measuring hemoglobin A1c. J Diabetes Sci Technol. 2009;3(3):439-45.
Consensus Committee. Consensus statement on the worldwide standardization of the hemoglobin A1C measurement: the American Diabetes Association, European Association for the Study of Diabetes, International Federation of Clinical Chemistry and Laboratory Medicine, and the International Diabetes Federation. Diabetes Care. 2007;30(9):2399-400.
Little RR, Rohlfing CL, Sacks DB, National Glycohemoglobin Standardization Program (NGSP) Steering Committee. Status of hemoglobin A1c measurement and goals for improvement: from chaos to order for improving diabetes care. Clin Chem. 2011;57(2):205-14.
Lenters-Westra E, Schindhelm RK, Bilo HJ, Slingerland RJ. Haemoglobin A1c: Historical overview and current concepts. Diabetes Res Clin Pract. 2013;99(2): 75-84.
National Kidney Foundation. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 update. Am J Kidney Dis. 2012;60(5):850-86.
Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014;63(5):713-35.
Weycamp C. HbA1c: a review of analytical and clinical aspects. Ann Lab Med. 2013;33(6):393-400.
Penttilä I, Penttilä K, Holm P, Laitinen H, Ranta P, Törrönen J, et al. Methods, units and quality requirements for the analysis of haemoglobin A1c in diabetes mellitus. World J Methodol. 2016;6(2):133-42.
Finke A, Kobold U, Hoelzel W, Weycamp C, Jeppsson JO, Miedema K. Preparation of a candidate primary reference material for the international standardisation of HbA1c determinations. Clin Chem Lab Med. 1998;36(5):299-308.
Fitzgibbons JF, Koler RD, Jones RT. Red cell age-related changes in hemoglobin A1a+b and A1c in normal and diabetic subjects. J Clin Invest. 1976; 58:3892–98.
Thom CS, Dickson CF, Gell DA, Weiss MJ. Hemoglobin variants: biochemical properties and clinical correlates. Cold Spring Harb Perspect Med. 2013;3(3):a011858.
Bunn HF, Haney DN, Kamin S, Gabbay KH, Gallop PM. The biosynthesis of human hemoglobin A1c. Slow glycosylation of hemoglobin in vivo. J Clin Invest. 1976;57(6):1652-9.
Trivelli LA, Ranney HM, Lai HT. Hemoglobin components in patients with diabetes mellitus. N Engl J Med. 1971;284(7): 353-57.
Shapiro R, McManus MJ, Zalut C, Bunn HF. Sites of nonenzymatic glycosylation of human hemoglobin A. J Biol Chem. 1980;255(7):3120-7.
Jeppsson JO, Kobold U, Barr J, Finke A, Hoelzel W, Hoshino T, et al. Approved IFCC reference method for the measurement of HbA1c in human blood. Clin Chem Lab Med. 2002;40(1):78-89.
Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ, et al. Translating the A1C assay into estimated average glucose values. Diabetes Care. 2008;31(8):1473-8.
Penttilä IM, Halonen T, Punnonen K, Tiikkainen U. Best use of the recommended IFCC reference method, material and values in HbA1C analyses. Scand J Clin Lab Invest. 2005;65(6):453-62.
Miller CD, Barnes CS, Phillips LS, Ziemer DC, Gallina DL, Cook CB, et al. Rapid A1c availability improves clinical decision-making in an urban primary care clinic. Diabetes Care. 2003;26(4):1158-63.
Flood D, Hawkins J, Rohloff P. A Home-Based Type 2 Diabetes Self-Management Intervention in Rural Guatemala. Prev Chronic Dis. 2017;14:E14-65.
Sacks DB, ADA/EASD/IDF Working Group of the HbA1c Assay. Global harmonization of hemoglobin A1c. Clin Chem. 2005;51(4):681-3.
Weykamp C, John WG, Mosca A, Hoshino T, Little R, Jeppsson JO, et al. The IFCC Reference Measurement System for HbA1c: a 6-year progress report. Clin Chem. 2008;54(2):240-8.
Hanas R, John WG; International HbA1c Consensus Committee. 2013 Update on the worldwide standardization of the hemoglobin A1c measurement. Pediatric Diabetes. 2014;15(3):e1-2.
Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurements. Lancet 1986;1(8476):307-10.
Giavarina D. Understanding Bland Altman analysis. Biochem Med (Zagreb). 2015;25(2):141-51.
Mosca A, Lapolla A, Gillery P. Glycemic control in the clinical management of diabetic patients. Clin Chem Lab Med. 2013;51(4):753-66.
Lenters-Westra E, Slingerland RJ. Six of eight hemoglobin A1c point-of-care instruments do not meet the general accepted analytical performance criteria. Clin Chem. 2010;56(1):44-52.
Goodall I, Colman PG, Schneider HG, McLean M, Barker G. Desirable performance standards for HbA1c analysis-precision, accuracy and standardization: consensus statement of the Australian Association of Clinical Biochemists (AACB), the Australian Diabetes Society (ADS), the Royal College of Pathologists of Australia (RCPA), Endocrine Society of Australia (ESA), and the Australian Diabetes Educators Association (ADEA). Clin Chem Lab Med. 2007;45(8):1083-97.
Unger G, Ruiz G, Milano P, Benozzi SF, Pennacchiotti GL. Evaluación del desempeño analítico de tres métodos de cuantificación de hemoglobina A1c. Acta Bioquím Clín Latinoam. 2014;48 (2):183-9.
Weykamp CW, Mosca A, Gillery P, Panteghini M. The analytical goals for hemoglobin A(1c) measurement in IFCC units and National Glycohemoglobin Standardization Program Units are different. Clin Chem. 2011;57(8):1204-6.
Lapolla A, Mosca A, Fedele D. The general use of glycated haemoglobin for the diagnosis of diabetes and other categories of glucose intolerance: still a long way to go. Nutr Metab Cardiovasc Dis. 2011;21(7):467-75.
Mongia SK, Little RR, Rohlfing CL, Hanson S, Roberts RF, Owen WE, et al. Effects of hemoglobin C and S traits on the results of 14 commercial glycated hemoglobin assays. Am J Clin Pathol. 2008;130(1):136-40.
Puukka R, Puukka M. Effect of hemoglobin F on measurements of hemoglobin A1c with physicians’ office analyzers. Clin Chem. 1994;40(2):342-3.
Goldstein DE, Little RR, Lorenz RA, Malone JI, Nathan D, Peterson CM. Tests of glycemia in diabetes. Diabetes Care. 1995;18(6):896-909.
English E, Idris I, Smith G, Dhatariya K, Kilpatrick ES, John WG. The effect of anaemia and abnormalities of erythrocyte indices on HbA1c analysis: a systematic review. Diabetologia. 2015;58(7):1409-21.
Tarim O, Küçükerdoğan A, Günay U, Eralp O, Ercan I. Effects of iron deficiency anemia on hemoglobin A1c in type 1 diabetes mellitus. Pediatr Int. 1999;41(4):357-62.
Coban E, Ozdogan M, Timuragaoglu A. Effect of iron deficiency anemia on the levels of hemoglobin A1c in nondiabetic patients. Acta Haematol. 2004;112(3):126-8.
Hashimoto K, Noguchi S, Morimoto Y, Hamada S, Wasada K, Imai S, et al. A1C but not serum glycated albumin is elevated in late pregnancy owing to iron deficiency. Diabetes Care. 2008;31(10):1945-8.
Penttilä I, Penttilä K, Holm P, Laitinen H, Rauramaa R. Hemoglobin A1c reported in units and diagnostic cut-offs in relation to the international recommendations. Clin Chem Lab Med. 2015;53(9):e215-7.
Guevara A, Chico M, Calvopiña M, Guderian RH. Hemoglobinopatías en comunidades de raza negra de los ríos Cayapas y Onzoles, cantón Eloy Alfaro, provincia de Esmeraldas, Ecuador. Biomédica. 1998;18(2):122-8.
Domínguez Y, Zurita C, Calvopiña D, Villacís J, Mora M. Prevalence of common hemoglobin variants in an afro-descendent Ecuadorian population. BMC Res Notes. 2013;6:132.
Jara NO, Guevara Espinoza A, Guderian RH. [Abnormal hemoglobins in Negroid Ecuadorian populations]. Sangre (Barc). 1989;34(1):10-3.
Saaddine JB, Fagot-Campagna A, Rolka D, Narayan KM, Geiss L, Eberhardt M, et al. Distribution of HbA(1c) levels for children and young adults in the U.S.: Third National Health and Nutrition Examination Survey. Diabetes Care. 2002;25(8):1326-30.
Menke A, Rust KF, Savage PJ, Cowie CC. Hemoglobin A1c, fasting plasma glucose, and 2-hour plasma glucose distributions in U.S. population subgroups: NHANES 2005-2010. Ann Epidemiol. 2014 Feb;24(2):83-9.
Avilés-Santa ML, Hsu LL, Arredondo M, Menke A, Werner E, Thyagarajan B, et al. Differences in Hemoglobin A1c Between Hispanics/Latinos and Non-Hispanic Whites: An Analysis of the Hispanic Community Health Study/Study of Latinos and the 2007-2012 National Health and Nutrition Examination Survey. Diabetes Care. 2016;39(6):1010-7.
Szymezak J, Lavalard E, Martin M, Leroy N, Gillery P. Carbamylated hemoglobin remains a critical issue in HbA1c measurements. Clin Chem Lab Med. 2009;47(5):612-3.
Peacock TP, Shihabi ZK, Bleyer AJ, Dolbare EL, Byers JR, Knovich MA, et al. Comparison of glycated albumin and hemoglobin A(1c) levels in diabetic subjects on hemodialysis. Kidney Int. 2008;73(9):1062-8.
Inaba M, Okuno S, Kumeda Y, Yamada S, Imanishi Y, Tabata T, et al. Glycated albumin is a better glycemic indicator than glycated hemoglobin values in hemodialysis patients with diabetes: effect of anemia and erythropoietin injection. J Am Soc Nephrol. 2007;18(3):896-903.
Freedman BI, Shenoy RN, Planer JA, Clay KD, Shihabi ZK, Burkart JM, et al. Comparison of glycated albumin and hemoglobin A1c concentrations in diabetic subjects on peritoneal and hemodialysis. Perit Dial Int. 2010;30(1):72-9.
Freedman BI, Shihabi ZK, Andries L, Cardona CY, Peacock TP, Byers JR, et al. Relationship between assays of glycemia in diabetic subjects with advanced chronic kidney disease. Am J Nephrol. 2010;31(5):375-9.
Stim J, Shaykh M, Anwar F, Ansari A, Arruda JA, Dunea G. Factors determining hemoglobin carbamylation in renal failure. Kidney Int. 1995;48(5):1605-10.
Smith WG, Holden M, Benton M, Brown CB. Glycosylated and carbamylated haemoglobin in uraemia. Nephrol Dial Transplant. 1989;4(2):96-100.
Smith WG, Holden M, Benton M, Brown CB. Carbamylated haemoglobin in chronic renal failure. Clin Chim Acta. 1988;178(3):297-303.
Li Q, Ju Y, Jin T, Pang B, Deng J, Du T et al. Haemoglobin A1c measurement in patients with chronic kidney disease. Clin Biochem. 2014;47(6):481-4.
Balion CM, Draisey TF, Thibert RJ. Carbamylated hemoglobin and carbamylated plasma protein in hemodialyzed patients. Kidney Int. 1998;53(2):488-95.
Jaisson S, Pietrement C, Gillery P. Carbamylation-derived products: bioactive compounds and potential biomarkers in chronic renal failure and atherosclerosis. Clin Chem. 2011;57(11):1499-505.
Weykamp CW, Penders TJ, Siebelder CW, Muskiet FA, Van der Slik W. Interference of carbamylated and acetylated hemoglobins in assays of glycohemoglobin by HPLC, electrophoresis, affinity chromatography, and enzyme immunoassay. Clin Chem. 1993;39(1):138-42.
Weykamp CW, Penders TJ, Muskiet FA, Van der Slik W. Influence of hemoglobin variants and derivatives on glycohemoglobin determinations, as investigated by 102 laboratories using 16 methods. Clin Chem. 1993;39(8):1717-23.
Flückiger R, Harmon W, Meier W, Loo S, Gabbay KH. Hemoglobin carbamylation in uremia. N Engl J Med. 1981;304(14):823-7.
Dolscheid-Pommerich RC, Kirchner S, Weigel C, Eichhorn L, Conrad R, Stoffel-Wagner B, et al. Impact of carbamylation on three different methods, HPLC, capillary electrophoresis and TINIA of measuring HbA1c levels in patients with kidney disease. Diabetes Res Clin Pract. 2015;108(1):15-22.
Nicolas C, Jaisson S, Gorisse L, Tessier FJ, Niquet-Léridon C, Jacolot P, et al. Carbamylation is a competitor of glycation for protein modification in vivo. Diabetes Metab. 2017 Jul 6. pii: S1262-3636(17)30104-0 [en prensa].
Berg AH, Drechsler C, Wenger J, Buccafusca R, Hod T, Kalim S, et al. Carbamylation of serum albumin as a risk factor for mortality in patients with kidney failure. Sci Transl Med. 2013;5(175):175ra29.
Delanghe S, Delanghe JR, Speeckaert R, Van Biesen W, Speeckaert MM. Mechanisms and consequences of carbamoylation. Nat Rev Nephrol. 2017;13(9):580-93.
Rahbar S. An abnormal haemoglobin in red cells of diabetes. Clin Chim Acta. 1968;22(2):296-8.
Rahbar S, Blumenfeld O, Ranney HM. Studies of an unusual hemoglobin in patients with diabetes mellitus. Biochem Biophys Res Commun. 1969;36(5):838-43.
Rahbar S. The discovery of glycated hemoglobin: a major event in the study of nonenzymatic chemistry in biological systems. Ann N Y Acad Sci. 2005;1043:9-19.
