ORIGINAL ARTICLES
July 2015 30. Lambert M, Lupien PJ, Gagne C, Levy E, Blaichman S, Langlois S, et al. Treatment of familial hypercholesterolemia in children and adolescents: effect of lovastatin. Canadian Lovastatin in Children Study Group. Pediatrics 1996;97:619-28. 31. de Ferranti S, Ludwig DS. Storm over statins—the controversy surrounding pharmacologic treatment of children. N Engl J Med 2008; 359:1309-12. 32. Loughlin J, Quinn S, Rivero E, Wong J, Huang J, Kralstein J, et al. Tegaserod and the risk of cardiovascular ischemic events:
an observational cohort study. J Cardiovasc Pharmacol Ther 2010;15:151-7. 33. Dore DD, Ziyadeh N, Cai B, Clifford CR, Norman H, Seeger JD. A crosssectional study of the identification of prevalent asthma and chronic obstructive pulmonary disease among initiators of long-acting beta-agonists in health insurance claims data. BMC Pulm Med 2014;14:47. 34. Vinci SR, Rifas-Shiman SL, Cheng JK, Mannix RC, Gillman MW, de Ferranti SD. Cholesterol testing among children and adolescents during health visits. JAMA 2014;311:1804-7.
50 Years Ago in THE JOURNAL OF PEDIATRICS Fatal Infection in a Newborn Infant Due to Herpes Simplex Virus Wright HT, Miller A. J Pediatr 1965;67:130-2
W
right and Miller describe an infant with disseminated herpes simplex virus infection, the first case in which the diagnosis was established pre-mortem. Since this article appeared, viral diagnostics have been revolutionized by the introduction of polymerase chain reaction (PCR)-based assays, in which segments of organism-specific nucleic acid are replicated from minute to large, identifiable quantities within hours. PCR technology was an amalgamation of many different discoveries in nucleic acid biology made during the 1960s and 1970s, including the characterization of DNA polymerases and the observation that replication requires an oligonucleotide primer to get the synthesis started. The technique involves a series of steps: heat-denaturization to split apart the double strand, followed by annealing of specific primers on either side of the segment of interest, followed by polymerization of the complementary strands, followed by heat-denaturization of the newly synthesized DNA, and so on; in this way, the quantity of the segment increases exponentially with repeated cycles. The technique was introduced conceptually in a 1971 publication, but its practical development began 12 years later at the biotechnology company Cetus Corporation. Key to this development was the use of the DNA polymerase from the hot-springs bacterium Thermus aquaticus. This enzyme remains stable at the high temperatures required to denature the DNA, allowing the process to be automated without the need to refresh polymerase with each cycle. The importance of PCR in medical diagnostics, indeed, in nearly all aspects of scientific endeavor, cannot be overstated. Thus it was not surprising when the development of the technique was awarded a Nobel Prize in 1993, to Cetus scientist Kary Mullis, who purportedly put the idea together while driving his Honda Civic on a California highway. Mullis received a $10 000 bonus from Cetus for his work with PCR in the mid-1980s; less than 5 years later the technology was sold to another company for $300 million. By the year 2000, over 3% of PubMed citations referred to PCR. Today it is an invaluable technique in virtually all the natural sciences and in fields ranging from anthropology to forensics, and likely would have rendered the diagnosis of herpes simplex virus infection in the infant reported by Wright and Miller straightforward, as it has in many other previously difficult-to-diagnose infectious diseases. Philip Toltzis, MD Hadassah Medical Organization Jerusalem, Israel http://dx.doi.org/10.1016/j.jpeds.2015.01.024
Patterns of Lipid Lowering Therapy among Children Ages 8-20 Years
119
July 2015 30. Lambert M, Lupien PJ, Gagne C, Levy E, Blaichman S, Langlois S, et al. Treatment of familial hypercholesterolemia in children and adolescents: effect of lovastatin. Canadian Lovastatin in Children Study Group. Pediatrics 1996;97:619-28. 31. de Ferranti S, Ludwig DS. Storm over statins—the controversy surrounding pharmacologic treatment of children. N Engl J Med 2008; 359:1309-12. 32. Loughlin J, Quinn S, Rivero E, Wong J, Huang J, Kralstein J, et al. Tegaserod and the risk of cardiovascular ischemic events:
an observational cohort study. J Cardiovasc Pharmacol Ther 2010;15:151-7. 33. Dore DD, Ziyadeh N, Cai B, Clifford CR, Norman H, Seeger JD. A crosssectional study of the identification of prevalent asthma and chronic obstructive pulmonary disease among initiators of long-acting beta-agonists in health insurance claims data. BMC Pulm Med 2014;14:47. 34. Vinci SR, Rifas-Shiman SL, Cheng JK, Mannix RC, Gillman MW, de Ferranti SD. Cholesterol testing among children and adolescents during health visits. JAMA 2014;311:1804-7.
50 Years Ago in THE JOURNAL OF PEDIATRICS Fatal Infection in a Newborn Infant Due to Herpes Simplex Virus Wright HT, Miller A. J Pediatr 1965;67:130-2
W
right and Miller describe an infant with disseminated herpes simplex virus infection, the first case in which the diagnosis was established pre-mortem. Since this article appeared, viral diagnostics have been revolutionized by the introduction of polymerase chain reaction (PCR)-based assays, in which segments of organism-specific nucleic acid are replicated from minute to large, identifiable quantities within hours. PCR technology was an amalgamation of many different discoveries in nucleic acid biology made during the 1960s and 1970s, including the characterization of DNA polymerases and the observation that replication requires an oligonucleotide primer to get the synthesis started. The technique involves a series of steps: heat-denaturization to split apart the double strand, followed by annealing of specific primers on either side of the segment of interest, followed by polymerization of the complementary strands, followed by heat-denaturization of the newly synthesized DNA, and so on; in this way, the quantity of the segment increases exponentially with repeated cycles. The technique was introduced conceptually in a 1971 publication, but its practical development began 12 years later at the biotechnology company Cetus Corporation. Key to this development was the use of the DNA polymerase from the hot-springs bacterium Thermus aquaticus. This enzyme remains stable at the high temperatures required to denature the DNA, allowing the process to be automated without the need to refresh polymerase with each cycle. The importance of PCR in medical diagnostics, indeed, in nearly all aspects of scientific endeavor, cannot be overstated. Thus it was not surprising when the development of the technique was awarded a Nobel Prize in 1993, to Cetus scientist Kary Mullis, who purportedly put the idea together while driving his Honda Civic on a California highway. Mullis received a $10 000 bonus from Cetus for his work with PCR in the mid-1980s; less than 5 years later the technology was sold to another company for $300 million. By the year 2000, over 3% of PubMed citations referred to PCR. Today it is an invaluable technique in virtually all the natural sciences and in fields ranging from anthropology to forensics, and likely would have rendered the diagnosis of herpes simplex virus infection in the infant reported by Wright and Miller straightforward, as it has in many other previously difficult-to-diagnose infectious diseases. Philip Toltzis, MD Hadassah Medical Organization Jerusalem, Israel http://dx.doi.org/10.1016/j.jpeds.2015.01.024
Patterns of Lipid Lowering Therapy among Children Ages 8-20 Years
119
