Objective: The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org). Evidence: This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocri...

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Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline

National High Blood Pressure Education Program.

Publisher Summary This chapter discusses the role of glutathione (GSH) and glutathione s-transferases in metabolism of chemical carcinogens and other electrophilic agents. GSH is a tripeptide (I) that is present in nearly all living cells and is the most abundant sulfhydryl compound present in animal tissues, mainly in the cytosol. The chapter illustrates the wide range of electrophilic agents, including several known mutagens and carcinogens, which conjugate with GSH, a process usually catalyzed by the GSH S-transferases. This conjugation is probably a protective mechanism and is the initial stage in mercapturic acid biosynthesis for the elimination of foreign compounds from the body. GSH S-transferases provide protection not only by catalyzing the conjugation of a potential toxicant with GSH, but also by preferentially binding, even covalently, that toxicant. The reactive electrophiles that conjugate with GSH also bind to DNA, RNA, and protein and identification of GSH conjugates provide information on the nature of these biologically active intermediates or even their immediate precursors. Thus, the knowledge of the way in which mutagens and carcinogens are metabolized is essential to a better understanding of their mode of action and of the processes for their detoxication.

The role of glutathione and glutathione S-transferases in the metabolism of chemical carcinogens and other electrophilic agents.

It is a major goal of clinical pharmacology to understand the dose-effect relationship in therapeutics. Much progress towards this goal has been made in the last 2 decades through the development of pharmacokinetics as a discipline. The study of pharmacokinetics seeks to explain the time course of drug concentration in the body. Recognition of the crucial concepts of clearance and volume of distribution has provided an important link to the physiological determinants of drug disposition. Mathematical models of absorption, distribution, metabolism and elimination have been extensively applied, and generally their predictions agree remarkably well with actual observations. However, the time course of drug concentration cannot in itself predict the time course or magnitude of drug effect. When drug concentrations at the effect site have reached equilibrium and the response is constant, the concentration-effect relationship is known as pharmacodynamics. Mathematical models of pharmacodynamics have been used widely by pharmacologists to describe drug effects on isolated tissues. The crucial concepts of pharmacodynamics are potency — reflecting the sensitivity of the organ or tissue to a drug, and efficacy — describing the maximum response. These concepts have been embodied in a simple mathematical expression, the Emax model, which provides a practical tool for predicting drug response analogous to the compartmental model in pharmacokinetics for predicting drug concentration.

Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models.

The role of alterations in membrane lipid composition in enabling physiological adaptation of organisms to their physical environment.

Results from a survey of 30,650 dentists and 30,547 chairside assistants suggest that long-term exposure to trace anesthetics in the dental operatory can be associated with increased general health problems and reproductive difficulties. Incidences of spontaneous abortion, congenital abnormalities in offspring, cancer, liver disease, and kidney disease were compared among exposed, nonexposed, and indirectly exposed persons.

Occupational Disease in Dentistry and Chronic Exposure to Trace Anesthetic Gases

Surgery during pregnancy and fetal outcome

The effect of two inhalation anesthetics of the order of spin-labeled phospholipid vesicles

A multiple logistic regression analysis of 12,914 pregnancies and 10,523 live births, based on a mail survey of professional women in medicine, was carried out to determine the relationship between maternal cigarette smoking, and spontaneous abortion and congenital abnormality. After controlling for interfering variables (age, exposure to trace anesthetic gases, pregnancy history, and mailing response), a statistically significant increase in risk associated with maternal cigarette smoking was found for spontaneous abortions and congenital abnormalities. The risk of spontaneous abortion for the heavy smoker is estimated to be as much as 1.7 times that of the nonsmoker in certain risk groups. The risk for congenital abnormality for babies born of smoking mothers is estimated to be as much as 2.3 times that of the nonsmoker, depending on age, pregnancy history, and other factors.

Cigarette smoking during pregnancy and the occurrence of spontaneous abortion and congenital abnormality

All male members of the American Society of Oral Surgeons and a sample of the American Dental Association membership were surveyed for exposure to anesthetic gases and the incidences of certain health problems. Concentrations of waste inhalation anesthetic gases in the dental surgery are several times those found in hospital operating rooms. This study establishes a relationship between exposure to waste gases and the incidence of health problems including spontaneous abortion in spouses, congenital abnormalities in offspring, and cancer and liver disease. Measurable concentrations of waste anesthetic gases have been found in hospital dental operating rooms. A mail survey of 4,797 general dental practitioners and 2,642 oral surgeons indicated that 20.2% of the general practitioners and 74.8% of the oral surgeons had anesthetic exposures exceeding three hours per week. In the comparison of the health of individuals exposed or unexposed to inhalation anesthetics, there was a significant increase (78%) of spontaneous abortion in the spouses of exposed dentists and a significant increase (156%) in liver disease for exposed dentists. The implication of these findings and possible solutions are discussed.

Ellis N. Cohen

Papers

Occupational Disease in Dentistry and Chronic Exposure to Trace Anesthetic Gases

Surgery during pregnancy and fetal outcome

The effect of two inhalation anesthetics of the order of spin-labeled phospholipid vesicles

Cigarette smoking during pregnancy and the occurrence of spontaneous abortion and congenital abnormality

A survey of anesthetic health hazards among dentists