EDITORIAL
A Tribute to Dr. Hermann R. Ochs, 1943–2013 David J. Greenblatt, MD
I
first met Hermann R. Ochs in the fall of 1975. He had come to Harvard Medical School as a research fellow, working under the mentorship of internationally-known scientists such as Thomas W. Smith, Eugene S. Braunwald, Edgar Haber, and Steven F. Vatner. I was a young faculty member of age similar to Hermann, and we launched into a scientific research collaboration and personal friendship that lasted until the day of his death. We shared an interest in clinical pharmacology and in the fate and effects of cardiovascular and psychotropic drugs in humans. More importantly, we shared a common view of the irony, both humorous and cruel, of human behavior and international politics which was to sustain our friendship for nearly 4 decades. Hermann and I were both born during World War II, but our childhood years were very different. I grew up “protected” in the United States, but Hermann was immersed in the tragedy and complexity of wartime, and of postwar Europe. I learned that Hermann was born approximately a year after his older brother, Rudolf, had died in battle. As such, Hermann’s birth was a blessing that came from tragedy—he never forgot this. Hermann grew up in Hamm, at the time a city of approximately 60,000 population. After completing Arbitur training in Hamm, he received his Medical Doctor degree in Marburg, then served as an intern both in Germany and at McGill University in Montreal. He trained as a resident in internal medicine in Giessen and Bonn, finishing in 1975. Hermann completed his Boston fellowship in 1977, and returned to Germany. We vowed that our research work together, and our friendship, would continue despite the distance. We made good on the vow. Over the next decade we each made numerous trips to each other’s homeland. Typically Hermann would arrive at the Boston airport with many freezer boxes full of samples from clinical studies that he and his colleagues and students had done in Bonn or Soest. We would analyze the samples in our laboratories in Boston, and then spend hours dictating scientific papers for publication. Following from his interest in cardiovascular pharmacology, Hermann’s initial work with Tom Smith of Harvard involved some of the very early studies of specific antibodies in the treatment of digitalis toxicity.1,2 In 1978 he published a highly-cited review article on spironolactone in the American Heart Journal,3 and in 1980 he had 2 separate articles on cardiovascular drug interactions published in the same month in the New England Journal of Medicine.4,5 Over the next decade Hermann, I, and Dr Richard I. Shader developed and shared an intense interest in alterations in drug disposition in relation to age and gender, in particular for the class of benzodiazepine derivatives. Many collaborative studies on this topic were conducted by Hermann Ochs and colleagues, and became important contributions to the literature in clinical pharmacology.6–13 Hermann also completed studies on topics such as benzodiazepine disposition in renal insufficiency14–18 and cirrhosis,19–21 and the effects of cigarette smoking and alcohol consumption on the pharmacokinetics of the benzodiazepines.22–25 He developed experimental models to study processes of hepatic and enteric presystemic extraction,26,27 and factors influencing drug uptake into cerebrospinal fluid and brain tissue.28–30 To this day we continue to rely upon the findings from his work. The cross-Atlantic research collaboration resulted in more than 100 research publications, and Hermann’s work on the hypothalamic-pituitary effects of digitalis glycosides31 was recognized by the McKeen-Cattell Award from the American College of Clinical Pharmacology. He also received the prestigious appointment as Professor at the University of Bonn. But the best part of the collaboration was spending time with Hermann. He was a student of World War II, and so was I. We made many trips together to historic landmarks in Europe. During one trip to the Normandy Beaches and battlegrounds in France, Hermann looked out over a field with hundreds of graves of British and American war casualties. His comment was, “no German losses?” Hermann’s view was that the cruelty and tragedy of the war did not prevent the continuation of cruelty and tragedy in the postwar era. The stupidity of human behavior persisted, and the predictable and unresolvable conflicts based on ideology, ethnicity, religion, and economics inevitably lead to violence, with the death of young people being the ultimate result.
From the Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA. Reprints: David J. Greenblatt, MD, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111 (e‐mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0271-0749 DOI: 10.1097/JCP.0000000000000241
Journal of Clinical Psychopharmacology • Volume 34, Number 6, December 2014
www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
669
Journal of Clinical Psychopharmacology • Volume 34, Number 6, December 2014
Editorial
We always thought of Hermann as “not the marrying kind.” Then in the late 1970s he met the beautiful and talented young physician, Birgitt Verburg. She was it. The announcement arrived in the mail early in 1982: “Wir haben geheiratet.” Hermann was a year short of 40. He moved to the small city of Soest to become Chief of Medicine at the Marien-Krankenhaus. Birgitt and Hermann had 3 sons, of whom they were fiercely proud. Hermann Ochs had a relentless determination to acquire and share knowledge. He devoured newspapers, periodicals, and historical items. By regular mail, fax, and e-mail, he sent me countless books, articles, pictures, and documents, including family documents dating back to wartime. He always included his own handwritten commentary, which combined irony and humor. The topics were religion, politics, ethnicity, historical fact, and historical fraud. He had plenty to say about the attempted assassination of Ronald Reagan, the death of Rudolf Hess, the fall of the Soviet Union, the reunification of Germany (“It will not be so easy”—he was right), the Middle East wars, and September 11. In the e-mail era of the last 15 years, communication in both directions became absurdly easy. I received literally hundreds of e-mail forwards from Hermann—sometimes several per day. All were ironic, cynical, and humorous. I last heard from him on June 19, 2013—there was no hint that he was ill. On June 25, I sent him a link to the old Soviet national anthem. I pointed out that the current national anthem of the Russian Republic, although the words have been revised, is otherwise identical. He was too ill to respond, and passed away 2 weeks later due to a rapidly-progressive blood dyscrasia. Hermann had retired—not voluntarily—from his position at Marien-Krankenhaus in 2008. I expect that he was relieved to be free of the burdens of hospital politics, but he seemed initially to be perplexed by retirement. “You can only read so many newspapers in a day,” he said. “You can exercise only so many hours in a day.” But in the more recent years, I got the impression that he was learning how to be retired, and was starting to have fun with it. A tragedy that he could not follow that through. He is a scientist and a friend that I will not forget.
10. Friedman H, Greenblatt DJ, Scavone JM, et al. Clearance of the antihistamine doxylamine reduced in elderly men but not in elderly women. Clin Pharmacokinet. 1989;16:312–316. 11. Greenblatt DJ, Divoll MK, Abernethy DR, et al. Age and gender effects on chlordiazepoxide kinetics: relation to antipyrine disposition. Pharmacology. 1989;38:327–334. 12. Greenblatt DJ, Friedman H, Burstein ES, et al. Trazodone kinetics: effect of age, gender, and obesity. Clin Pharmacol Ther. 1987;42:193–200. 13. Olubodun JO, Ochs HR, von Moltke LL, et al. Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men. Br J Clin Pharmacol. 2003;56:297–304. 14. Ochs HR, Greenblatt DJ, Kaschell HJ, et al. Diazepam kinetics in patients with renal insufficiency or hyperthyroidism. Br J Clin Pharmacol. 1981;12:829–832. 15. Ochs HR, Greenblatt DJ, Klehr U. Disposition of oxazepam in patients on maintenance hemodialysis. Klin Wochenschr. 1984;62:765–767. 16. Ochs HR, Greenblatt DJ, Labedzki L, et al. Alprazolam kinetics in patients with renal insufficiency. J Clin Psychopharmacol. 1986;6:292–294 17. Ochs HR, Oberem U, Greenblatt DJ. Nitrazepam clearance unimpaired in patients with renal insufficiency. J Clin Psychopharmacol. 1992;12: 183–185. 18. Ochs HR, Rauh HW, Greenblatt DJ, et al. Clorazepate dipotassium and diazepam in renal insufficiency: serum concentrations and protein binding of diazepam and desmethyldiazepam. Nephron. 1984;37:100–104. 19. Ochs HR, Greenblatt DJ, Eckardt B, et al. Repeated diazepam dosing in cirrhotic patients: cumulation and sedation. Clin Pharmacol Ther. 1983;33: 471–476. 20. Ochs HR, Greenblatt DJ, Verburg-Ochs B, et al. Temazepam clearance unaltered in cirrhosis. Am J Gastroenterol. 1986;81:80–84. 21. Ochs HR, Greenblatt DJ, Knüchel M. Effect of cirrhosis and renal failure on the kinetics of clotiazepam. Eur J Clin Pharmacol. 1986;30:89–92. 22. Ochs HR, Greenblatt DJ, Burstein ES. Lack of influence of cigarette smoking on triazolam pharmacokinetics. Br J Clin Pharmacol. 1987;23:759–763. 23. Ochs HR, Greenblatt DJ, Knüchel M. Kinetics of diazepam, midazolam, and lorazepam in cigarette smokers. Chest. 1985;87:223–226.
REFERENCES 1. Ochs HR, Smith TW. Reversal of advanced digitoxin toxicity and modification of pharmacokinetics by specific antibodies and Fab fragments. J Clin Invest. 1977;60:1303–1313. 2. Ochs HR, Vatner SF, Smith TW. Reversal of inotropic effects of digoxin by specific antibodies and their Fab fragments in the conscious dog. J Pharmacol Exp Ther. 1978;207(1):64–71. 3. Ochs HR, Greenblatt DJ, Bodem G, et al. Spironolactone. Am Heart J. 1978;96:389–400. 4. Ochs HR, Pabst J, Greenblatt DJ, et al. Noninteraction of digitoxin and quinidine. N Engl J Med. 1980;303:672–674. 5. Ochs HR, Carstens G, Greenblatt DJ. Reduction in lidocaine clearance during continuous infusion and by coadministration of propranolol. N Engl J Med. 1980;303:373–377. 6. Ochs HR, Greenblatt DJ, Woo E, et al. Reduced quinidine clearance in elderly persons. Am J Cardiol. 1978;42:481–485. 7. Ochs HR, Greenblatt DJ, Friedman H, et al. Bromazepam pharmacokinetics: influence of age, gender, oral contraceptives, cimetidine, and propranolol. Clin Pharmacol Ther. 1987;41:562–570. 8. Ochs HR, Greenblatt DJ, Otten H. Disposition of oxazepam in relation to age, sex, and cigarette smoking. Klin Wochenschr. 1981;59:899–903. 9. Ochs HR, Greenblatt DJ, Divoll M, et al. Diazepam kinetics in relation to age and sex. Pharmacology. 1981;23:24–30.
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www.psychopharmacology.com
24. Ochs HR, Greenblatt DJ, Locniskar A, et al. Influence of propranolol coadministration or cigarette smoking on the kinetics of desmethyldiazepam following intravenous clorazepate. Klin Wochenschr. 1986;64:1217–1221. 25. Ochs HR, Greenblatt DJ, Arendt RM, et al. Pharmacokinetic noninteraction of triazolam and ethanol. J Clin Psychopharmacol. 1984;4:106–107. 26. Ochs HR, Greenblatt DJ, Eichelkraut W, et al. Hepatic vs. gastrointestinal presystemic extraction of oral midazolam and flurazepam. J Pharmacol Exp Ther. 1987;243:852–856. 27. Ochs HR, Greenblatt DJ, Eichelkraut W, et al. Contribution of the gastrointestinal tract to lorazepam conjugation and clonazepam nitroreduction. Pharmacology. 1991;42:36–48. 28. Ochs HR, Greenblatt DJ, Abernethy DR, et al. Cerebrospinal fluid uptake and peripheral distribution of centrally acting drugs: relation to lipid solubility. J Pharm Pharmacol. 1985;25:204–209. 29. Greenblatt DJ, Ochs HR, Lloyd BL. Entry of diazepam and its major metabolite into cerebrospinal fluid. Psychopharmacology (Berl). 1980;70:89–93. 30. Ochs HR, Greenblatt DJ, Lloyd BL, et al. Entry of quinidine into cerebrospinal fluid. Am Heart J. 1980;100(3):341–346. 31. Bellmann O, Ochs HR, Knüchel M, et al. Evaluation of the hypothalamic-pituitary effects of digoxin. J Clin Pharmacol. 1984;24: 474–479.
© 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
A Tribute to Dr. Hermann R. Ochs, 1943–2013 David J. Greenblatt, MD
I
first met Hermann R. Ochs in the fall of 1975. He had come to Harvard Medical School as a research fellow, working under the mentorship of internationally-known scientists such as Thomas W. Smith, Eugene S. Braunwald, Edgar Haber, and Steven F. Vatner. I was a young faculty member of age similar to Hermann, and we launched into a scientific research collaboration and personal friendship that lasted until the day of his death. We shared an interest in clinical pharmacology and in the fate and effects of cardiovascular and psychotropic drugs in humans. More importantly, we shared a common view of the irony, both humorous and cruel, of human behavior and international politics which was to sustain our friendship for nearly 4 decades. Hermann and I were both born during World War II, but our childhood years were very different. I grew up “protected” in the United States, but Hermann was immersed in the tragedy and complexity of wartime, and of postwar Europe. I learned that Hermann was born approximately a year after his older brother, Rudolf, had died in battle. As such, Hermann’s birth was a blessing that came from tragedy—he never forgot this. Hermann grew up in Hamm, at the time a city of approximately 60,000 population. After completing Arbitur training in Hamm, he received his Medical Doctor degree in Marburg, then served as an intern both in Germany and at McGill University in Montreal. He trained as a resident in internal medicine in Giessen and Bonn, finishing in 1975. Hermann completed his Boston fellowship in 1977, and returned to Germany. We vowed that our research work together, and our friendship, would continue despite the distance. We made good on the vow. Over the next decade we each made numerous trips to each other’s homeland. Typically Hermann would arrive at the Boston airport with many freezer boxes full of samples from clinical studies that he and his colleagues and students had done in Bonn or Soest. We would analyze the samples in our laboratories in Boston, and then spend hours dictating scientific papers for publication. Following from his interest in cardiovascular pharmacology, Hermann’s initial work with Tom Smith of Harvard involved some of the very early studies of specific antibodies in the treatment of digitalis toxicity.1,2 In 1978 he published a highly-cited review article on spironolactone in the American Heart Journal,3 and in 1980 he had 2 separate articles on cardiovascular drug interactions published in the same month in the New England Journal of Medicine.4,5 Over the next decade Hermann, I, and Dr Richard I. Shader developed and shared an intense interest in alterations in drug disposition in relation to age and gender, in particular for the class of benzodiazepine derivatives. Many collaborative studies on this topic were conducted by Hermann Ochs and colleagues, and became important contributions to the literature in clinical pharmacology.6–13 Hermann also completed studies on topics such as benzodiazepine disposition in renal insufficiency14–18 and cirrhosis,19–21 and the effects of cigarette smoking and alcohol consumption on the pharmacokinetics of the benzodiazepines.22–25 He developed experimental models to study processes of hepatic and enteric presystemic extraction,26,27 and factors influencing drug uptake into cerebrospinal fluid and brain tissue.28–30 To this day we continue to rely upon the findings from his work. The cross-Atlantic research collaboration resulted in more than 100 research publications, and Hermann’s work on the hypothalamic-pituitary effects of digitalis glycosides31 was recognized by the McKeen-Cattell Award from the American College of Clinical Pharmacology. He also received the prestigious appointment as Professor at the University of Bonn. But the best part of the collaboration was spending time with Hermann. He was a student of World War II, and so was I. We made many trips together to historic landmarks in Europe. During one trip to the Normandy Beaches and battlegrounds in France, Hermann looked out over a field with hundreds of graves of British and American war casualties. His comment was, “no German losses?” Hermann’s view was that the cruelty and tragedy of the war did not prevent the continuation of cruelty and tragedy in the postwar era. The stupidity of human behavior persisted, and the predictable and unresolvable conflicts based on ideology, ethnicity, religion, and economics inevitably lead to violence, with the death of young people being the ultimate result.
From the Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA. Reprints: David J. Greenblatt, MD, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111 (e‐mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0271-0749 DOI: 10.1097/JCP.0000000000000241
Journal of Clinical Psychopharmacology • Volume 34, Number 6, December 2014
www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
669
Journal of Clinical Psychopharmacology • Volume 34, Number 6, December 2014
Editorial
We always thought of Hermann as “not the marrying kind.” Then in the late 1970s he met the beautiful and talented young physician, Birgitt Verburg. She was it. The announcement arrived in the mail early in 1982: “Wir haben geheiratet.” Hermann was a year short of 40. He moved to the small city of Soest to become Chief of Medicine at the Marien-Krankenhaus. Birgitt and Hermann had 3 sons, of whom they were fiercely proud. Hermann Ochs had a relentless determination to acquire and share knowledge. He devoured newspapers, periodicals, and historical items. By regular mail, fax, and e-mail, he sent me countless books, articles, pictures, and documents, including family documents dating back to wartime. He always included his own handwritten commentary, which combined irony and humor. The topics were religion, politics, ethnicity, historical fact, and historical fraud. He had plenty to say about the attempted assassination of Ronald Reagan, the death of Rudolf Hess, the fall of the Soviet Union, the reunification of Germany (“It will not be so easy”—he was right), the Middle East wars, and September 11. In the e-mail era of the last 15 years, communication in both directions became absurdly easy. I received literally hundreds of e-mail forwards from Hermann—sometimes several per day. All were ironic, cynical, and humorous. I last heard from him on June 19, 2013—there was no hint that he was ill. On June 25, I sent him a link to the old Soviet national anthem. I pointed out that the current national anthem of the Russian Republic, although the words have been revised, is otherwise identical. He was too ill to respond, and passed away 2 weeks later due to a rapidly-progressive blood dyscrasia. Hermann had retired—not voluntarily—from his position at Marien-Krankenhaus in 2008. I expect that he was relieved to be free of the burdens of hospital politics, but he seemed initially to be perplexed by retirement. “You can only read so many newspapers in a day,” he said. “You can exercise only so many hours in a day.” But in the more recent years, I got the impression that he was learning how to be retired, and was starting to have fun with it. A tragedy that he could not follow that through. He is a scientist and a friend that I will not forget.
10. Friedman H, Greenblatt DJ, Scavone JM, et al. Clearance of the antihistamine doxylamine reduced in elderly men but not in elderly women. Clin Pharmacokinet. 1989;16:312–316. 11. Greenblatt DJ, Divoll MK, Abernethy DR, et al. Age and gender effects on chlordiazepoxide kinetics: relation to antipyrine disposition. Pharmacology. 1989;38:327–334. 12. Greenblatt DJ, Friedman H, Burstein ES, et al. Trazodone kinetics: effect of age, gender, and obesity. Clin Pharmacol Ther. 1987;42:193–200. 13. Olubodun JO, Ochs HR, von Moltke LL, et al. Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men. Br J Clin Pharmacol. 2003;56:297–304. 14. Ochs HR, Greenblatt DJ, Kaschell HJ, et al. Diazepam kinetics in patients with renal insufficiency or hyperthyroidism. Br J Clin Pharmacol. 1981;12:829–832. 15. Ochs HR, Greenblatt DJ, Klehr U. Disposition of oxazepam in patients on maintenance hemodialysis. Klin Wochenschr. 1984;62:765–767. 16. Ochs HR, Greenblatt DJ, Labedzki L, et al. Alprazolam kinetics in patients with renal insufficiency. J Clin Psychopharmacol. 1986;6:292–294 17. Ochs HR, Oberem U, Greenblatt DJ. Nitrazepam clearance unimpaired in patients with renal insufficiency. J Clin Psychopharmacol. 1992;12: 183–185. 18. Ochs HR, Rauh HW, Greenblatt DJ, et al. Clorazepate dipotassium and diazepam in renal insufficiency: serum concentrations and protein binding of diazepam and desmethyldiazepam. Nephron. 1984;37:100–104. 19. Ochs HR, Greenblatt DJ, Eckardt B, et al. Repeated diazepam dosing in cirrhotic patients: cumulation and sedation. Clin Pharmacol Ther. 1983;33: 471–476. 20. Ochs HR, Greenblatt DJ, Verburg-Ochs B, et al. Temazepam clearance unaltered in cirrhosis. Am J Gastroenterol. 1986;81:80–84. 21. Ochs HR, Greenblatt DJ, Knüchel M. Effect of cirrhosis and renal failure on the kinetics of clotiazepam. Eur J Clin Pharmacol. 1986;30:89–92. 22. Ochs HR, Greenblatt DJ, Burstein ES. Lack of influence of cigarette smoking on triazolam pharmacokinetics. Br J Clin Pharmacol. 1987;23:759–763. 23. Ochs HR, Greenblatt DJ, Knüchel M. Kinetics of diazepam, midazolam, and lorazepam in cigarette smokers. Chest. 1985;87:223–226.
REFERENCES 1. Ochs HR, Smith TW. Reversal of advanced digitoxin toxicity and modification of pharmacokinetics by specific antibodies and Fab fragments. J Clin Invest. 1977;60:1303–1313. 2. Ochs HR, Vatner SF, Smith TW. Reversal of inotropic effects of digoxin by specific antibodies and their Fab fragments in the conscious dog. J Pharmacol Exp Ther. 1978;207(1):64–71. 3. Ochs HR, Greenblatt DJ, Bodem G, et al. Spironolactone. Am Heart J. 1978;96:389–400. 4. Ochs HR, Pabst J, Greenblatt DJ, et al. Noninteraction of digitoxin and quinidine. N Engl J Med. 1980;303:672–674. 5. Ochs HR, Carstens G, Greenblatt DJ. Reduction in lidocaine clearance during continuous infusion and by coadministration of propranolol. N Engl J Med. 1980;303:373–377. 6. Ochs HR, Greenblatt DJ, Woo E, et al. Reduced quinidine clearance in elderly persons. Am J Cardiol. 1978;42:481–485. 7. Ochs HR, Greenblatt DJ, Friedman H, et al. Bromazepam pharmacokinetics: influence of age, gender, oral contraceptives, cimetidine, and propranolol. Clin Pharmacol Ther. 1987;41:562–570. 8. Ochs HR, Greenblatt DJ, Otten H. Disposition of oxazepam in relation to age, sex, and cigarette smoking. Klin Wochenschr. 1981;59:899–903. 9. Ochs HR, Greenblatt DJ, Divoll M, et al. Diazepam kinetics in relation to age and sex. Pharmacology. 1981;23:24–30.
670
www.psychopharmacology.com
24. Ochs HR, Greenblatt DJ, Locniskar A, et al. Influence of propranolol coadministration or cigarette smoking on the kinetics of desmethyldiazepam following intravenous clorazepate. Klin Wochenschr. 1986;64:1217–1221. 25. Ochs HR, Greenblatt DJ, Arendt RM, et al. Pharmacokinetic noninteraction of triazolam and ethanol. J Clin Psychopharmacol. 1984;4:106–107. 26. Ochs HR, Greenblatt DJ, Eichelkraut W, et al. Hepatic vs. gastrointestinal presystemic extraction of oral midazolam and flurazepam. J Pharmacol Exp Ther. 1987;243:852–856. 27. Ochs HR, Greenblatt DJ, Eichelkraut W, et al. Contribution of the gastrointestinal tract to lorazepam conjugation and clonazepam nitroreduction. Pharmacology. 1991;42:36–48. 28. Ochs HR, Greenblatt DJ, Abernethy DR, et al. Cerebrospinal fluid uptake and peripheral distribution of centrally acting drugs: relation to lipid solubility. J Pharm Pharmacol. 1985;25:204–209. 29. Greenblatt DJ, Ochs HR, Lloyd BL. Entry of diazepam and its major metabolite into cerebrospinal fluid. Psychopharmacology (Berl). 1980;70:89–93. 30. Ochs HR, Greenblatt DJ, Lloyd BL, et al. Entry of quinidine into cerebrospinal fluid. Am Heart J. 1980;100(3):341–346. 31. Bellmann O, Ochs HR, Knüchel M, et al. Evaluation of the hypothalamic-pituitary effects of digoxin. J Clin Pharmacol. 1984;24: 474–479.
© 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
