Over the last decade, we have witnessed major advances in the understanding of the molecular basis of neonatal and infancy-onset diabetes. It is now widely accepted that diabetes presenting before 6 months of age is unlikely to be autoimmune type 1 diabetes. The vast majority of such patients will have a monogenic disorder responsible for the disease and, in some of them, also for a number of other associated extrapancreatic clinical features. Reaching a molecular diagnosis will have immediate clinical consequences for about half of affected patients, as identification of a mutation in either of the two genes encoding the ATP-sensitive potassium channel allows switching from insulin injections to oral sulphonylureas. It also facilitates genetic counselling within the affected families and predicts clinical prognosis. Importantly, monogenic diabetes seems not to be limited to the first 6 months but extends to some extent into the second half of the first year of life, when type 1 diabetes is the more common cause of diabetes. From a scientific perspective, the identification of novel genetic aetiologies has provided important new knowledge regarding the development and function of the human pancreas.

1.
Schwartzman J, Crusius ME, Beirne DP: Diabetes mellitus in infants under one year of age; report of a case and review of the literature. Am J Dis Child 1947;74:587-606.
2.
Keidan SE: Transient diabetes in infancy. Arch Dis Child 1955;30:291-296.
3.
Iafusco D, Stazi MA, Cotichini R, Cotellessa M, Martinucci ME, Mazzella M, Cherubini V, Barbetti F, Martinetti M, Cerutti F, Prisco F, Early Onset Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology: Permanent diabetes mellitus in the first year of life. Diabetologia 2002;45:798-804, erratum in Diabetologia 2003;46:140.
4.
Rosenbauer J, Herzig P, von Kries R, Neu A, Giani G: Temporal, seasonal, and geographical incidence patterns of type I diabetes mellitus in children under 5 years of age in Germany. Diabetologia 1999;42:1055-1059.
5.
Grulich-Henn J, Wagner V, Thon A, Schober E, Marg W, Kapellen TM, Haberland H, Raile K, Ellard S, Flanagan SE, Hattersley AT, Holl RW: Entities and frequency of neonatal diabetes: data from the diabetes documentation and quality management system (DPV). Diabet Med 2010;27:709-712.
6.
von Mühlendahl KE, Herkenhoff H: Long-term course of neonatal diabetes. N Engl J Med 1995;333:704-708.
7.
Porter JR, Barrett TG: Acquired non-type 1 diabetes in childhood: subtypes, diagnosis, and management. Arch Dis Child 2004;89:1138-1144.
8.
Concannon P, Rich SS, Nepom GT: Genetics of type 1A diabetes. N Engl J Med 2009;360:1646-1654.
9.
Erlich H, Valdes AM, Noble J, Carlson JA, Varney M, Concannon P, Mychaleckyj JC, Todd JA, Bonella P, Fear AL, Lavant E, Louey A, Moonsamy P: Type 1 Diabetes Genetics Consortium. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes 2008;57:1084-1092.
10.
Komulainen J, Kulmala P, Savola K, Lounamaa R, Ilonen J, Reijonen H, Knip M, Akerblom HK: Clinical, autoimmune, and genetic characteristics of very young children with type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group. Diabetes Care 1999;22:1950-1955.
11.
Edghill EL, Dix RJ, Flanagan SE, Bingley PJ, Hattersley AT, Ellard S, Gillespie KM: HLA genotyping supports a nonautoimmune etiology in patients diagnosed with diabetes under the age of 6 months. Diabetes 2006;55:1895-1898.
12.
Schatz D, Krischer J, Horne G, Riley W, Spillar R, Silverstein J, Winter W, Muir A, Derovanesian D, Shah S, et al: Islet cell antibodies predict insulin-dependent diabetes in United States school age children as powerfully as in unaffected relatives. J Clin Invest 1994;93:2403-2407.
13.
Wenzlau JM, Juhl K, Yu L, Moua O, Sarkar SA, Gottlieb P, Rewers M, Eisenbarth GS, Jensen J, Davidson HW, Hutton JC: The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci USA 2007;104:17040-17045.
14.
Lindberg B, Ivarsson SA, Landin-Olsson M, Sundkvist G, Svanberg L, Lernmark A: Islet autoantibodies in cord blood from children who developed type I (insulin-dependent) diabetes mellitus before 15 years of age. Diabetologia 1999;42:181-187.
15.
Achenbach P, Bonifacio E, Koczwara K, Ziegler AG: Natural history of type 1 diabetes. Diabetes 2005;54(suppl 2):S25-S31.
16.
Kimpimäki T, Kupila A, Hämäläinen AM, Kukko M, Kulmala P, Savola K, Simell T, Keskinen P, Ilonen J, Simell O, Knip M: The first signs of beta-cell autoimmunity appear in infancy in genetically susceptible children from the general population: the Finnish Type 1 Diabetes Prediction and Prevention Study. J Clin Endocrinol Metab 2001;86:4782-4788.
17.
Rubio-Cabezas O, Minton JA, Caswell R, Shield JP, Deiss D, Sumnik Z, Cayssials A, Herr M, Loew A, Lewis V, Ellard S, Hattersley AT: Clinical heterogeneity in patients with FOXP3 mutations presenting with permanent neonatal diabetes. Diabetes Care 2009;32:111-116.
18.
Cardwell CR, Stene LC, Joner G, Davis EA, Cinek O, Rosenbauer J, Ludvigsson J, Castell C, Svensson J, Goldacre MJ, Waldhoer T, Polanska J, Gimeno SG, Chuang LM, Parslow RC, Wadsworth EJ, Chetwynd A, Pozzilli P, Brigis G, Urbonaite B, Sipetić S, Schober E, Ionescu-Tirgoviste C, de Beaufort CE, Stoyanov D, Buschard K, Patterson CC: Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data. Diabetologia 2010;53:641-651.
19.
Gicquel C, Le Bouc Y: Hormonal regulation of fetal growth. Horm Res 2006;65(suppl 3):28-33.
20.
Hattersley A, Bruining J, Shield J, Njolstad P, Donaghue KC: The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2009;10(suppl 12):33-42.
21.
Massa O, Iafusco D, D'Amato E, Gloyn AL, Hattersley AT, Pasquino B, Tonini G, Dammacco F, Zanette G, Meschi F, Porzio O, Bottazzo G, Crinó A, Lorini R, Cerutti F, Vanelli M, Barbetti F, Early Onset Diabetes Study Group of the Italian Society of Pediatric Endocrinology and Diabetology: KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes. Hum Mutat 2005;25:22-27.
22.
Rubio-Cabezas O, Flanagan SE, Damhuis A, Hattersley AT, Ellard S: K(ATP) channel mutations in infants with permanent diabetes diagnosed after 6 months of life. Pediatr Diabetes 2012;13:322-325.
23.
Murphy R, Ellard S, Hattersley AT: Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Nat Clin Pract Endocrinol Metab 2008;4:200-213.
24.
Flanagan SE, Patch AM, Mackay DJ, Edghill EL, Gloyn AL, Robinson D, Shield JP, Temple K, Ellard S, Hattersley AT: Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. Diabetes 2007;56:1930-1937, erratum in Diabetes 2008;57:523.
25.
Edghill EL, Flanagan SE, Patch AM, Boustred C, Parrish A, Shields B, Shepherd MH, Hussain K, Kapoor RR, Malecki M, MacDonald MJ, Støy J, Steiner DF, Philipson LH, Bell GI, Neonatal Diabetes International Collaborative Group, Hattersley AT, Ellard S: Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes 2008;57:1034-1042.
26.
Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, Howard N, Srinivasan S, Silva JM, Molnes J, Edghill EL, Frayling TM, Temple IK, Mackay D, Shield JP, Sumnik Z, van Rhijn A, Wales JK, Clark P, Gorman S, Aisenberg J, Ellard S, Njølstad PR, Ashcroft FM, Hattersley AT: Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med 2004;350:1838-1849, erratum in N Engl J Med 2004;351:1470.
27.
Gloyn AL, Reimann F, Girard C, Edghill EL, Proks P, Pearson ER, Temple IK, Mackay DJ, Shield JP, Freedenberg D, Noyes K, Ellard S, Ashcroft FM, Gribble FM, Hattersley AT: Relapsing diabetes can result from moderately activating mutations in KCNJ11. Hum Mol Genet 2005;14:925-934.
28.
Babenko AP, Polak M, Cavé H, Busiah K, Czernichow P, Scharfmann R, Bryan J, Aguilar-Bryan L, Vaxillaire M, Froguel P: Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med 2006;355:456-466.
29.
Clark RH, McTaggart JS, Webster R, Mannikko R, Iberl M, Sim XL, Rorsman P, Glitsch M, Beeson D, Ashcroft FM: Muscle dysfunction caused by a KATP channel mutation in neonatal diabetes is neuronal in origin. Science 2010;329:458-461.
30.
Gloyn AL, Diatloff-Zito C, Edghill EL, Bellanné-Chantelot C, Nivot S, Coutant R, Ellard S, Hattersley AT, Robert JJ: KCNJ11 activating mutations are associated with developmental delay, epilepsy and neonatal diabetes syndrome and other neurological features. Eur J Hum Genet 2006;14:824-830.
31.
Ellard S, Flanagan SE, Girard CA, Patch AM, Harries LW, Parrish A, Edghill EL, Mackay DJ, Proks P, Shimomura K, Haberland H, Carson DJ, Shield JP, Hattersley AT, Ashcroft FM: Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. Am J Hum Genet 2007;81:375-382.
32.
Pearson ER, Flechtner I, Njølstad PR, Malecki MT, Flanagan SE, Larkin B, Ashcroft FM, Klimes I, Codner E, Iotova V, Slingerland AS, Shield J, Robert JJ, Holst JJ, Clark PM, Ellard S, Søvik O, Polak M, Hattersley AT, Neonatal Diabetes International Collaborative Group: Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med 2006;355:467-477.
33.
Rafiq M, Flanagan SE, Patch AM, Shields BM, Ellard S, Hattersley AT, Neonatal Diabetes International Collaborative Group: Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations. Diabetes Care 2008;31:204-209.
34.
Klupa T, Skupien J, Mirkiewicz-Sieradzka B, Gach A, Noczynska A, Zubkiewicz-Kucharska A, Szalecki M, Kozek E, Nazim J, Mlynarski W, Malecki MT: Efficacy and safety of sulfonylurea use in permanent neonatal diabetes due to KCNJ11 gene mutations: 34-month median follow-up. Diabetes Technol Ther 2010;12:387-391.
35.
Slingerland AS, Nuboer R, Hadders-Algra M, Hattersley AT, Bruining GJ: Improved motor development and good long-term glycaemic control with sulfonylurea treatment in a patient with the syndrome of intermediate developmental delay, early-onset generalised epilepsy and neonatal diabetes associated with the V59M mutation in the KCNJ11 gene. Diabetologia 2006;49:2559-2563.
36.
Gurgel LC, Crispim F, Noffs MH, Belzunces E, Rahal MA, Moisés RS: Sulfonylrea treatment in permanent neonatal diabetes due to G53D mutation in the KCNJ11 gene: improvement in glycemic control and neurological function. Diabetes Care 2007;30:e108.
37.
Koster JC, Cadario F, Peruzzi C, Colombo C, Nichols CG, Barbetti F: The G53D mutation in Kir6.2 (KCNJ11) is associated with neonatal diabetes and motor dysfunction in adulthood that is improved with sulfonylurea therapy. J Clin Endocrinol Metab 2008;93:1054-1061.
38.
Støy J, Edghill EL, Flanagan SE, Ye H, Paz VP, Pluzhnikov A, Below JE, Hayes MG, Cox NJ, Lipkind GM, Lipton RB, Greeley SA, Patch AM, Ellard S, Steiner DF, Hattersley AT, Philipson LH, Bell GI, Neonatal Diabetes International Collaborative Group: Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci USA 2007;104:15040-15044.
39.
Polak M, Dechaume A, Cavé H, Nimri R, Crosnier H, Sulmont V, de Kerdanet M, Scharfmann R, Lebenthal Y, Froguel P, Vaxillaire M, French ND (Neonatal Diabetes) Study Group: Heterozygous missense mutations in the insulin gene are linked to permanent diabetes appearing in the neonatal period or in early infancy: a report from the French ND (Neonatal Diabetes) Study Group. Diabetes 2008;57:1115-1119.
40.
Colombo C, Porzio O, Liu M, Massa O, Vasta M, Salardi S, Beccaria L, Monciotti C, Toni S, Pedersen O, Hansen T, Federici L, Pesavento R, Cadario F, Federici G, Ghirri P, Arvan P, Iafusco D, Barbetti F, Early Onset Diabetes Study Group of the Italian Society of Pediatric Endocrinology and Diabetes (SIEDP): Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus. J Clin Invest 2008;118:2148-2156.
41.
Molven A, Ringdal M, Nordbø AM, Raeder H, Støy J, Lipkind GM, Steiner DF, Philipson LH, Bergmann I, Aarskog D, Undlien DE, Joner G, Søvik O, Norwegian Childhood Diabetes Study Group, Bell GI, Njølstad PR: Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. Diabetes 2008;57:1131-1135.
42.
Støy J, Greeley SA, Paz VP, Ye H, Pastore AN, Skowron KB, Lipton RB, Cogen FR, Bell GI, Philipson LH, United States Neonatal Diabetes Working Group: Diagnosis and treatment of neonatal diabetes: a United States experience. Pediatr Diabetes 2008;9:450-459.
43.
Russo L, Iafusco D, Brescianini S, Nocerino V, Bizzarri C, Toni S, Cerutti F, Monciotti C, Pesavento R, Iughetti L, Bernardini L, Bonfanti R, Gargantini L, Vanelli M, Aguilar-Bryan L, Stazi MA, Grasso V, Colombo C, Barbetti F, ISPED Early Diabetes Study Group: Permanent diabetes during the first year of life: multiple gene screening in 54 patients. Diabetologia 2011;54:1693-1701.
44.
Rubio-Cabezas O, Patch AM, Minton JA, Flanagan SE, Edghill EL, Hussain K, Balafrej A, Deeb A, Buchanan CR, Jefferson IG, Mutair A, Neonatal Diabetes International Collaborative Group, Hattersley AT, Ellard S: Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. J Clin Endocrinol Metab 2009;94:4162-4170, erratum in J Clin Endocrinol Metab 2010;95:1480.
45.
Habeb AM, Al-Magamsi MS, Eid IM, Ali MI, Hattersley AT, Hussain K, Ellard S: Incidence, genetics, and clinical phenotype of permanent neonatal diabetes mellitus in northwest Saudi Arabia. Pediatr Diabetes DOI: 10.1111/j.1399-5448.2011.00828.x.
46.
Temple IK, Gardner RJ, Mackay DJ, Barber JC, Robinson DO, Shield JP: Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes. Diabetes 2000;49:1359-1366.
47.
Temple IK, Shield JP: Transient neonatal diabetes, a disorder of imprinting. J Med Genet 2002;39:872-875.
48.
Mackay DJ, Boonen SE, Clayton-Smith J, Goodship J, Hahnemann JM, Kant SG, Njølstad PR, Robin NH, Robinson DO, Siebert R, Shield JP, White HE, Temple IK: A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus. Hum Genet 2006;120:262-269.
49.
Mackay DJ, Callaway JL, Marks SM, White HE, Acerini CL, Boonen SE, Dayanikli P, Firth HV, Goodship JA, Haemers AP, Hahnemann JM, Kordonouri O, Masoud AF, Oestergaard E, Storr J, Ellard S, Hattersley AT, Robinson DO, Temple IK: Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. Nat Genet 2008;40:949-951.
50.
Docherty LE, Kabwama S, Lehmann A, Hawke E, Harrison L, Flanagan SE, Ellard S, Hattersley AT, Shield JP, Ennis S, Mackay DJ, Temple IK: Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype-phenotype correlation in an international cohort of patients. Diabetologia 2013;56:758-762.
51.
Shield JP, Temple IK, Sabin M, Mackay D, Robinson DO, Betts PR, Carson DJ, Cavé H, Chevenne D, Polak M: An assessment of pancreatic endocrine function and insulin sensitivity in patients with transient neonatal diabetes in remission. Arch Dis Child Fetal Neonatal Ed 2004;89:F341-F343.
52.
Shield JP: Neonatal diabetes: how research unravelling the genetic puzzle has both widened our understanding of pancreatic development whilst improving children's quality of life. Horm Res 2007;67:77-83.
53.
Rubio-Cabezas O, Edghill EL, Argente J, Hattersley AT: Testing for monogenic diabetes among children and adolescents with antibody-negative clinically defined Type 1 diabetes. Diabet Med 2009;26:1070-1074.
54.
Allen HL, Flanagan SE, Shaw-Smith C, De Franco E, Akerman I, Caswell R, International Pancreatic Agenesis Consortium, Ferrer J, Hattersley AT, Ellard S: GATA6 haploinsufficiency causes pancreatic agenesis in humans. Nat Genet 2011;44:20-22.
55.
De Franco E, Shaw-Smith C, Flanagan SE, Shepherd MH, International NDM Consortium, Hattersley AT, Ellard S: GATA6 mutations cause a broad phenotypic spectrum of diabetes from pancreatic agenesis to adult-onset diabetes without exocrine insufficiency. Diabetes 2013;62:993-997.
56.
Smith SB, Qu HQ, Taleb N, Kishimoto NY, Scheel DW, Lu Y, Patch AM, Grabs R, Wang J, Lynn FC, Miyatsuka T, Mitchell J, Seerke R, Désir J, Eijnden SV, Abramowicz M, Kacet N, Weill J, Renard ME, Gentile M, Hansen I, Dewar K, Hattersley AT, Wang R, Wilson ME, Johnson JD, Polychronakos C, German MS: Rfx6 directs islet formation and insulin production in mice and humans. Nature 2010;463:775-780.
57.
Rubio-Cabezas O, Minton JA, Kantor I, Williams D, Ellard S, Hattersley AT: Homozygous mutations in NEUROD1 are responsible for a novel syndrome of permanent neonatal diabetes and neurological abnormalities. Diabetes 2010;59:2326-2331.
58.
Rubio-Cabezas O, Jensen JN, Hodgson MI, Codner E, Ellard S, Serup P, Hattersley AT: Permanent neonatal diabetes and enteric anendocrinosis associated with biallelic mutations in NEUROG3. Diabetes 2011;60:1349-1353.
59.
Solomon BD, Pineda-Alvarez DE, Balog JZ, Hadley D, Gropman AL, Nandagopal R, Han JC, Hahn JS, Blain D, Brooks B, Muenke M: Compound heterozygosity for mutations in PAX6 in a patient with complex brain anomaly, neonatal diabetes mellitus, and microophthalmia. Am J Med Genet A 2009;149A:2543-2546.
60.
Poulton CJ, Schot R, Kia SK, Jones M, Verheijen FW, Venselaar H, de Wit MC, de Graaff E, Bertoli-Avella AM, Mancini GM: Microcephaly with simplified gyration, epilepsy, and infantile diabetes linked to inappropriate apoptosis of neural progenitors. Am J Hum Genet 2011;89:265-276.
61.
Greeley SA, John PM, Winn AN, Ornelas J, Lipton RB, Philipson LH, Bell GI, Huang ES: The cost-effectiveness of personalized genetic medicine: the case of genetic testing in neonatal diabetes. Diabetes Care 2011;34:622-627.
62.
Barrett TG: Differential diagnosis of type 1 diabetes: which genetic syndromes need to be considered? Pediatr Diabetes 2007;8(suppl 6):15-23.
63.
Slingerland AS, Hattersley AT: Activating mutations in the gene encoding Kir6.2 alter fetal and postnatal growth and also cause neonatal diabetes. J Clin Endocrinol Metab 2006;91:2782-2788.
64.
Baumeister FA, Engelsberger I, Schulze A: Pancreatic agenesis as cause for neonatal diabetes mellitus. Klin Padiatr 2005;217:76-81.
65.
Bennett K, James C, Mutair A, Al-Shaikh H, Sinani A, Hussain K: Four novel cases of permanent neonatal diabetes mellitus caused by homozygous mutations in the glucokinase gene. Pediatr Diabetes 2011;12:192-196.
66.
Garin I, Edghill EL, Akerman I, Rubio-Cabezas O, Rica I, Locke JM, Maestro MA, Alshaikh A, Bundak R, del Castillo G, Deeb A, Deiss D, Fernandez JM, Godbole K, Hussain K, O'Connell M, Klupa T, Kolouskova S, Mohsin F, Perlman K, Sumnik Z, Rial JM, Ugarte E, Vasanthi T, Neonatal Diabetes International Group, Johnstone K, Flanagan SE, Martínez R, Castaño C, Patch AM, Fernández-Rebollo E, Raile K, Morgan N, Harries LW, Castaño L, Ellard S, Ferrer J, Perez de Nanclares G, Hattersley AT: Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis. Proc Natl Acad Sci USA 2010;107:3105-3110.
67.
Ellard S, Lango Allen H, De Franco E, Flanagan SE, Hysenaj G, Colclough K, Houghton JA, Shepherd M, Hattersley AT, Weedon MN, Caswell R: Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. Diabetologia 2013;56:1958-1963.
68.
Karges B, Meissner T, Icks A, Kapellen T, Holl RW: Management of diabetes mellitus in infants. Nat Rev Endocrinol 2011;8:201-211.
69.
Tubiana-Rufi N: Insulin pump therapy in neonatal diabetes. Endocr Dev 2007;12:67-74.
70.
Codner E, Flanagan S, Ellard S, García H, Hattersley AT: High-dose glibenclamide can replace insulin therapy despite transitory diarrhea in early-onset diabetes caused by a novel R201L Kir6.2 mutation. Diabetes Care 2005;28:758-759.
71.
Kumaraguru J, Flanagan SE, Greeley SA, Nuboer R, Støy J, Philipson LH, Hattersley AT, Rubio-Cabezas O: Tooth discoloration in patients with neonatal diabetes after transfer onto glibenclamide: a previously unreported side effect. Diabetes Care 2009;32:1428-1430.
72.
Rubio-Cabezas O, Flanagan SE, Edghill EL, Patch A-M, Ellard S, Hattersley AT: Parental consanguinity strongly influences genetic aetiology in permanent neonatal diabetes. 35th ISPAD Annu Conf, Ljubljana, September 2009.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.