David Meyers: A Case Study
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Over the next four years, Hale experimented with pigs and vitamin A deficiency and found other defects such as cleft lip and malformed hind legs. Hale's experiments established that an absence or deficiency of a nutrient could produce severe congenital malformations in mammalian embryos. In , pediatrician Sidney Q. Cohlan in New York City, New York, reported that large doses of vitamin A caused congenital malformations of the central nervous system and other systems in rats.
That announcement led to decades of experimentation with vitamin A and its derivatives, retinoids. In the s, thalidomide provided one of the first instances when governments enacted regulations regarding the risk of teratogens to the developing fetus. Thalidomide had been patented in and was approved for use in Europe as a sedative and anti-nausea medicine for pregnant women. After several years on the market, physicians noted that women who had taken thalidomide while pregnant gave birth to a increased number of infants with severe malformations such as shortened, absent, or extra limbs dysmelia , incomplete development or a below average number of cells bone hypoplasticity , and a variety of ear, heart, and internal organ defects.
In , physician Widukind Lenz in Hamburg, Germany reported his observations on thalidomide's teratogenicity and the drug was soon taken off the market. Kelsey requested more clinical test results after she received reports of the adverse effects of thalidomide in Europe. Approximately 10, babies worldwide were born with defects due to thalidomide. After the thalidomide incident, in August , the American Pharmaceutical Manufacturers Association implored the US pharmaceutical industry to establish a Commission on Drug Safety to develop ways of improving animal teratogenicity tests. In , James G.
Wilson at the University of Florida Medical School in Gainesville, Florida, refined the principles of teratology he had first introduced in at a conference on congenital malformations. Wilson's six principles of teratology state verbatim:. Alcohol, which also falls under the fourth category of teratogen, can cause Fetal Alcohol Syndrome FAS in children born to women who drank too much alcohol while pregnant. FAS can cause defects such as minor facial abnormalities and damage to the brain, which consequently leads to learning, behavioral, and cognitive abnormalities. In the US, pediatricians David W. Smith and Kenneth L.
Of the eight children observed, four had similar deficiencies in growth and cognitive development. This observation led Smith and Jones to investigate alcohol as a teratogen and over the next few years, the duo collected case studies of children born to alcoholic mothers to enumerate morphological anomalies and growth deficiencies associated with FAS. Today, the FDA monitors teratogen exposures to pregnant women in the US with a number of regulations and risk management programs. For example, the retinoic acid isotretinoin which is commonly used for acne treatment cannot be given to any patient unless they are enrolled in iPLEDGE, a risk management program designed to prevent fetal exposure to isotretinoin.
Teratogens By: Chanapa Tantibanchachai. Keywords: teratogenicity. Teratogens Teratogens are substances that may produce physical or functional defects in the human embryo or fetus after the pregnant woman is exposed to the substance. Wilson's six principles of teratology state verbatim: Sensitivity to teratogen-induced malformation depends on the genotype species of the conceptus. Sensitivity to teratogen-induced malformation varies during different developmental stages at the time of exposure, where there are critical periods of sensitivity to agents and organ systems. Teratogens act via a specific mechanism on developing cells and tissues to initiate a cascade of altered developmental events.
Teratogens produce a consistent deviation from normal development. Deviation can include: 1 death, 2 malformation, 3 growth retardation , or 4 functional defect. Teratogen-induced malformations occur in a dose-dependent manner, ranging from no observable defects to total lethality. Sources Allen, Victoria M. Anthony Armson. Angles, J. Walsh, K. Li, S. Barnett, and Marshall J. Barrow, Mark V. Brown-Woodman, Patricia D. Hadley, Janet Waterhose, and William S. Centers for Disease Control and Prevention. Chambers, Christina D. Johnson, Robert J. Felix, Lyn M. Dick, and Kenneth Lyons Jones. Clark, Owen E. Meckel, the Younger, to the Science of Teratology. Cockroft, David L. Cohlan, Sidney Q. Dareste, Camille.
Paris: E. Corresponding author: Vernon J. All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed. Department of Health and Human Services. Use of trade names and commercial sources is for identification only and does not imply endorsement by the U. CDC is not responsible for the content of pages found at these sites. This conversion might result in character translation or format errors in the HTML version. Skip directly to site content Skip directly to page options Skip directly to A-Z link.
Section Navigation. Facebook Twitter LinkedIn Syndicate. Minus Related Pages. Lee, PhD 1 ,3 View author affiliations View suggested citation. Summary What is already known about this topic? What is added by this report? What are the implications for public health practice? Article Metrics. Metric Details. Related Materials. PDF pdf icon [K]. Clin Infect Dis Epub March 23, Emerg Infect Dis Epub March 19, Epub March 27, Evaluation of the effectiveness of surveillance and containment measures for the first patients with COVID in Singapore—January 2—February 29, Lancet ;— N Engl J Med Epub March 12, Aerosol emission and superemission during human speech increase with voice loudness. Sci Rep ; Air, surface environmental, and personal protective equipment contamination by severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 from a symptomatic patient.
He was expected to report to a federal prison on October 12th, but remained free while his lawyers appealed his conviction Pappalardo, At the time of his conviction, Ebbers' lawyers claimed the judge in the case gave the jury inappropriate instructions about Ebbers' knowledge of WorldCom's accounting fraud Pappalardo, By January of , Reid Weingarten, Ebber's lawyer, was claiming that the previous trial was manipulated against Ebbers because three high level WorldCom executives were barred from testifying on Ebbers' behalf.
Twenty years does seem an awfully long time" MacIntyre, Weingarten went on to assert that the government "should have charged the three former WorldCom employees that could have helped exonerate Ebbers or let them go" Reporter, He charged, too, that "the jury was wrongly instructed that it could convict Ebbers on the basis of so-called "conscious avoidance" of knowledge of the fraud at WorldCom" Reporter, Perhaps most compellingly, Weingarten called into question the fairness of Ebbers' sentence that was five times as long as that given to ex-WorldCom financial chief Scott Sullivan Reporter, Weingarten's claims are not without merit. His relatively light sentence was part of a bargain wherein he agreed to plead guilty to the charges filed against him and to cooperate with prosecutors as they built a case against Ebbers.
In doing so, Sullivan became the prosecution's main witness against Ebbers and the only person to testify that he discussed the WorldCom fraud directly with Ebbers Ferranti, Others involved in the scandal were also treated less harshly than Ebbers. Allen, Judith Areen, Carl J. Aycock, Max E. Bobbitt, Clifford L. Alexander, Jr. Kellett, Jr. Macklin, John A. Porter, Bert C. Roberts, Jr. Sidgmore, and Lawrence C. Tucker, At the time of this update, Ebbers has been convicted by a court of law, but remains free on bail while he pursues an appeal. Although the extent of his punishment is under contention, one thing remains clear - that Ebbers and the other officers at WorldCom are guilty of presiding over what is to date, the largest corporate fraud in history.
Reprinted with permission. Alexander, Steve. Belson, Ken. Citigroup Inc.