School of Medicine

Wayne State University School of Medicine
Doctors denounce clinical trials of 'alternative' medicines
In Headlines on August 20, 2014
David Gorski, M.D., Ph.D.

David Gorski, M.D., Ph.D.

Experts writing in the journal Trends in Molecular Medicine’s Aug. 6 edition call for an end to clinical trials of “highly implausible treatments” such as homeopathy and reiki. During the last two decades, such complementary and alternative medicine treatments have been embraced in medical academia despite budget constraints and the fact that they rest on dubious science, they say.

The writers, David Gorski, M.D., Ph.D., F.A.C.S., associate professor of surgery and Breast Surgery Section chief of the Michael and Marian Ilitch Department of Surgery at the Wayne State University School of Medicine and medical director of the Alexander J. Walt Comprehensive Breast Center at the Barbara Ann Karmanos Cancer Institute, and Steven Novella, M.D., assistant professor of neurology at Yale University, argue that, in these cases, the medical establishment is essentially testing whether magic works. Dr. Gorski and Dr. Novella are editors for Science-Based Medicine (http://www.sciencebasedmedicine.org), an organization and blog dedicated to exploring the complicated relationship between science and medicine.

“We hope this will be the first of many opportunities to discuss in the peer-reviewed literature the perils and pitfalls of doing clinical trials on treatment modalities that have already been refuted by basic science,” Dr. Gorski said. “The two key examples in the article, homeopathy and reiki, are about as close to impossible from basic science considerations alone as you can imagine. Homeopathy involves diluting substances away to nothing and beyond, while reiki is in essence faith healing that substitutes Eastern mysticism for Christian beliefs, as can be demonstrated by substituting the word ‘god’ for the ‘universal source’ that reiki masters claim to be able to tap into to channel their ‘healing energy’ into patients.”

“Studying highly implausible treatments is a losing proposition,” Dr. Novella added. “Such studies are unlikely to demonstrate benefit, and proponents are unlikely to stop using the treatment when the study is negative. Such research only serves to lend legitimacy to otherwise dubious practices.”

What is needed, the doctors said, is science-based medicine rather than evidence-based medicine. Biologically plausible treatments should advance to randomized clinical trials only when there is sufficient preclinical evidence to justify the effort, time and expense, as well as the use of human subjects.

“Somehow this idea has sprung up that to be a ‘holistic’ doctor you have to embrace pseudoscience like homeopathy, reiki, traditional Chinese medicine and the like, but that’s a false dichotomy,” Dr. Gorski said. “If the medical system is currently too impersonal and patients are rushed through office visits because a doctor has to see more and more patients to cover his salary and expenses, then the answer is to find a way to fix those problems, not to embrace quackery. ‘Integrating’ pseudoscience with science-based medicine isn’t going to make science-based medicine better.  One of our bloggers, Mark Crislip, has a fantastic saying for this: ‘If you mix cow pie with apple pie, it does not make the cow pie taste better; it makes the apple pie worse.’ With CAM or ‘integrative medicine,’ that’s exactly what we’re doing, and these clinical trials of magic are just more examples of it.”

Dr. Gorski and Dr. Novella call on patients to exercise critical thinking skills when evaluating the evidence for or against any kind of treatment. “Critical thinking will help patients learn to recognize when a course of treatment is not supported by data or to tell when a health claim from any practitioner is just too good to be true,” Dr. Gorski said.

Trends in Molecular Medicine is published by Cell Press.
Michigan Academy of Family Physicians elects residency director Pierre Morris, M.D., to leadership role
In Headlines on August 20, 2014
Pierre Morris, M.D.

Pierre Morris, M.D.

Pierre Morris, M.D., was elected to serve a one-year term as vice president of the Michigan Academy of Family Physicians at its annual meeting July 18 in Lansing.

The Novi resident and assistant professor of Family Medicine and Public Health Sciences directs the Wayne State University School of Medicine’s family medicine and transitional year residency programs at Crittenton Hospital and Medical Center in Rochester, Mich. He also is chair of residency recruitment for his department, and completed his own family medicine residency with WSU in 2004.

The MAFP is the largest medical specialty organization in the state.

“The MAFP is a very active and multifaceted organization that continues to be highly successful advocating for and guiding the direction of family medicine locally and nationally,” Dr. Morris said. “I am highly honored to be associated with such a distinguished organization, and as vice president I plan to play an active role advancing our issues, assisting in the reduction of health care disparities, and accurately and appropriately defining the specialty of family medicine and our broad scope of clinical practice.”

Dr. Morris came to medicine after 13 years as a 10th and 11th grade biology teacher in Normandy, Mo.

“At 36, I started reassessing my life and thought, ‘where do I go from here, and what is it that my background would allow me to do?’ Medicine became an option,” he said.

He left his teaching job in 1996 and received his medical degree from Ross University School of Medicine in Portsmouth, Dominica, in December 2000. He moved to Michigan soon after and spent one semester teaching biology at Okemos High School to earn money while waiting for his WSU residency to start in July 2001.

As vice president of the MAFP, he will work with its president and board leadership to ensure that all board meetings and official proceedings of the organization are documented. He also will represent the board at functions and events as designated by the president, and will be one of the leading voices representing family physicians in local, state and national issues coverage.

“In Michigan and across the nation the chronic shortage of primary care physicians is evident, now compounded by the successful implementation of the Affordable Care Act. As vice president of the MAFP Board of Directors, and in my role as a residency program director, my top goals remain recruiting talented medical school graduates into the specialty of family medicine and addressing the growing demand for quality and comprehensive health care that only family medicine physicians can provide,” he added. “ I will advocate for increased Graduate Medical Education funding on the state and federal level with our Michigan legislators, with an overarching goal of educating physicians who will provide access to care for those most in need.”

Former psychiatry Professor Emanuel Tanay, 86, dies
In Headlines on August 19, 2014
Emanuel Tanay, M.D.

Emanuel Tanay, M.D.

Emanuel Tanay, M.D. who lent his expertise as an expert witness in thousands of court cases, including those of such well-known defendants as Jack Ruby, Theodore Bundy and Sam Sheppard, died in hospice care Aug. 5 of metastatic prostate cancer. He was 86.

A former professor of psychiatry and behavioral neurosciences for the Wayne State University School of Medicine and adjunct associate professor of the WSU Law School, he was a distinguished fellow of the Academy of Forensic Sciences and the American Psychiatric Association, and a champion of those suffering from psychic trauma and post-traumatic stress disorder.  He was among those who successfully lobbied the American Psychiatric Association to recognize PTSD as a diagnosable and treatable medical condition in its Diagnostic and Statistical Manual of Mental Disorders.

Dr. Tanay’s expertise in the area of psychic trauma was a direct result of his own personal experiences with post-traumatic stress disorder. As a teenage boy during World War II, he survived the Holocaust in Poland and Hungary by hiding from the Nazis and living on false papers to conceal the fact that he was Jewish. With his father confined to and later killed at the P³aszów concentration camp, Dr. Tanay became the leader of his family, saving the lives of his mother, his sister Olenka and his childhood sweetheart. He and his family were liberated in Budapest in 1945.

After the war, Dr. Tanay became a tireless defender for the rights of Holocaust survivors. Although he was a consultant for the German government in its attempts to provide compensation to survivors of the concentration camps, his main interest and concern was in the mental health of survivors. He became a visiting scholar at the Department of Holocaust and Genocide Studies at Stockton College in New Jersey. He was featured in the Oscar-nominated documentary, “Courage to Care” and also in the permanent exhibit, “Testimonies” on display at the National Holocaust Memorial Museum in Washington, D.C.

Murder was another subject Dr. Tanay built his reputation upon. The Detroit Free Press once described Emanuel Tanay as “probably the nation’s premier psychiatric theorist on homicide.”

After Jack Ruby’s conviction for the murder of Lee Harvey Oswald was overturned, Dr. Tanay was retained as a psychiatric forensic expert by the defense. In preparation for a second trial he conducted extensive interviews with the defendant and his two siblings. His work on Ruby’s behalf was cited several times in the Warren Commission Report on the Assassination of President Kennedy.

In 1989, Dr. Tanay appeared on a panel of the American Association of Psychiatry and the Law to discuss his work as an expert witness in the trial of serial killer Ted Bundy. Dr. Tanay wrote about his work with Bundy, Ruby, accused wife killer Sam Sheppard, and many other clients in his book, “American Legal Injustice: Behind the Scenes with an Expert Witness.”

Survivors include his wife, Sandra; son David; daughters Elaine and Anita; and six grandchildren.

Visitation will take place Sept. 13 at 11 a.m. at the Nie Family Funeral Home Liberty Road Chapel, 3767 W. Liberty Road, in Ann Arbor. A memorial service will follow at noon.

Dr. Walz named director of M.D.-Ph.D. program
In Headlines on August 19, 2014
Dan Walz, Ph.D.

Dan Walz, Ph.D.

Dan Walz, Ph.D., professor of physiology, has been appointed director of the Wayne State University School of Medicine’s M.D.-Ph.D. program.

“Dr. Walz, with his background and lifetime support of medical research, is just the driving force to take us into the next phase of the future of our M.D.-Ph.D. program,” said Dean Valerie M. Parisi, M.D., M.P.H., M.B.A., in announcing the appointment Aug. 18.

He replaces Ambika Mathur, Ph.D., professor of pediatrics, who earlier this year was appointed dean of the Wayne State University Graduate School.

Dr. Walz will retain his role as associate dean of Research and Graduate Programs.

He joined the WSU Department of Physiology in 1973. He served for 10 years as the university’s vice president for Research before his appointment as associate dean of Research for the School of Medicine. He is a former dean of the Graduate School.

“Enhancing the physician-scientist workforce is a major national and institutional goal,” Dr. Walz said, “and I look forward to recruiting the best students to our MD-PhD program from throughout the nation since Wayne State University provides such a unique environment for training in clinical and translational sciences.”

The program director for three National Institutes of Health-supported institutional training grants, Dr. Walz has directed the dissertation work of 10 doctoral students and trained eight post-doctoral fellows. His research interests are in the structure and function of procoagulant plasma proteins as well as proteins secreted by activated platelets.

Dr. Walz received a bachelor of science degree in biology and chemistry from St. John Fisher College in Rochester, N.Y. He holds a master’s degree in biochemistry from St. Louis University and received his doctorate degree in physiology from Wayne State University.

Science features advances in understanding of preterm birth and discoveries made at Perinatology Research Branch, WSU, DMC
In Headlines on August 15, 2014
Roberto Romero, M.D., D.Med.Sci.

Roberto Romero, M.D., D.Med.Sci.

Labor (term and preterm) is characterized by increased myometrial contractility, cervical dilatation, and rupture of the chorioamniotic membranes. Collectively, these events have been referred to as the common pathway of parturition. The switch of the myometrium from a quiescent to a contractile state is associated with a change in nuclear progesterone receptor isoforms and an increase in the expression of the miR-200 family, as well as an increase in estrogen receptor a signaling. Cervical ripening is mediated by changes in extracellular matrix proteins, as well as alterations in epithelial barrier and immune surveillance properties. Decidual or membrane activation, in close proximity to the cervix, occurs in preparation for membrane rupture and to facilitate separation of the chorioamniotic membranes and placenta from the uterus. E denotes extracellular matrix; M, mucus; Os, cervical os.
Credit: Courtesy Science

Labor (term and preterm) is characterized by increased myometrial contractility, cervical dilatation, and rupture of the chorioamniotic membranes. Collectively, these events have been referred to as the common pathway of parturition. The switch of the myometrium from a quiescent to a contractile state is associated with a change in nuclear progesterone receptor isoforms and an increase in the expression of the miR-200 family, as well as an increase in estrogen receptor a signaling. Cervical ripening is mediated by changes in extracellular matrix proteins, as well as alterations in epithelial barrier and immune surveillance properties. Decidual or membrane activation, in close proximity to the cervix, occurs in preparation for membrane rupture and to facilitate separation of the chorioamniotic membranes and placenta from the uterus. E denotes extracellular matrix; M, mucus; Os, cervical os. Credit: Courtesy Science

Proposed mechanisms of disease implicated in spontaneous preterm labor. Genetic and environmental factors are likely contributors to each mechanism.
Credit: Courtesy Science

Proposed mechanisms of disease implicated in spontaneous preterm labor. Genetic and environmental factors are likely contributors to each mechanism. Credit: Courtesy Science

A subset of patients with preterm labor has placental vascular lesions, including failure of physiologic transformation of the uterine spiral arteries. (A) Schematic drawing of the maternal fetal interface in normal pregnancy. A physiologically transformed uterine spiral artery with a wide lumen delivers blood to the chorionic villi of the placenta. (B) A spiral artery with an expanded ostium that normally enables adequate perfusion of the chorionic villi. (C) Ostium of a narrow spiral artery with failure of physiologic transformation in a patient with spontaneous preterm labor. (D) Periodic acid–Schiff staining of a histological section of the maternal-fetal interface in normal pregnancy shows a spiral artery transformed by cytokeratin 7–positive cytotrophoblasts (brown) that line the lumen. (E) Failure of physiologic transformation of a spiral artery in a patient with preterm labor. The lumen is narrow, and cytotrophoblasts have not invaded the muscular wall.
Credit: Courtesy Science

A subset of patients with preterm labor has placental vascular lesions, including failure of physiologic transformation of the uterine spiral arteries. (A) Schematic drawing of the maternal fetal interface in normal pregnancy. A physiologically transformed uterine spiral artery with a wide lumen delivers blood to the chorionic villi of the placenta. (B) A spiral artery with an expanded ostium that normally enables adequate perfusion of the chorionic villi. (C) Ostium of a narrow spiral artery with failure of physiologic transformation in a patient with spontaneous preterm labor. (D) Periodic acid–Schiff staining of a histological section of the maternal-fetal interface in normal pregnancy shows a spiral artery transformed by cytokeratin 7–positive cytotrophoblasts (brown) that line the lumen. (E) Failure of physiologic transformation of a spiral artery in a patient with preterm labor. The lumen is narrow, and cytotrophoblasts have not invaded the muscular wall. Credit: Courtesy Science

The Aug. 15 edition of the prestigious journal Science features a major article about the most important problem in obstetrics: preterm labor. The article, “Preterm labor: one syndrome, many causes,” delivers a powerful message: preterm birth is not one condition, but many, and provides a framework for meeting this challenge.

“There are 15 million preterm babies born annually, and the condition affects 5 percent to 15 percent of all pregnancies, with the highest rates in North America and Africa. Prematurity is the leading cause of infant death up to age 1and the second-leading cause of childhood death before the age of 5,” said Roberto Romero, M.D., D.Med.Sci., chief of the Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development located at Wayne State University and the Detroit Medical Center. “We have made progress by identifying the causes of premature labor, and now we propose that it is possible to reframe the problem and make it tractable.”

A common belief is that preterm labor is merely labor that starts too soon. This perception derives from the fact that labor, whether term or preterm, has the same features – increased uterine contractility, opening of the cervix and rupture of the membranes. “However,” Dr. Romero said, “the fundamental difference is that normal labor at term occurs when the uterus and placenta cannot continue to support the growth of the fetus within the womb. In contrast, preterm labor results from several disease states.”

Dr. Romero considers premature labor a syndrome – a collection of syndromes and signs – caused by multiple disease processes. A typical example of these disease processes is a “silent” intra-amniotic infection. Bacteria normally present in the vagina sometimes ascend into the amniotic cavity, triggering inflammation that in turn initiates premature labor.

From an evolutionary perspective, Dr. Romero explained, the onset of premature labor in the context of infection can be considered to have survival value, because it allows the mother to expel infected tissue (the membranes and fluid) and maintain reproductive fitness for a future pregnancy. This unique mechanism of maternal host defense comes at a price: prematurity.

Physicians and scientists at the PRB are now asking why some women develop a “silent” infection that can cause preterm labor and rupture of membranes, and some do not.

Other patients do not have infection, but have other disease states. For example, some women present with vaginal bleeding and uterine contractions, and they have inadequate blood supply to the placenta. Studies at the PRB, WSU and DMC show that some patients with premature labor have very narrow spiral arteries, which fail to expand and do not provide sufficient blood supply to the placenta. Researchers are investigating biomarkers in maternal blood that can identify these patients.

Another fascinating discovery is that maternal anti-fetal rejection can explain some cases of premature labor. The fetus and placenta express both maternal and paternal antigens, and are therefore allografts (or transplants). The placenta has been considered the most successful transplant in nature. However, sometimes the mother rejects the paternal antigens expressed in the placenta, and this causes preterm labor. New research taking place at WSU, DMC and the PRB is focused on the identification of biomarkers responsible for maternal anti-fetal rejection.

Premature labor can also begin by a decline in progesterone action. Progesterone is essential for the maintenance of pregnancy and keeps the cervix closed until the onset of labor at term. A decline in progesterone action leads to a short cervix, which predisposes to premature labor. The administration of vaginal progesterone to patients with a short cervix can reduce the rate of preterm birth by 45 percent, as well as the rate of respiratory distress syndrome, the most common complication in premature babies. A policy of universal cervical screening is being implemented in Detroit, coupled with the administration of vaginal progesterone.

“Progress in the prevention of premature labor will require deciphering the mechanisms of disease, the identification of specific biomarkers and implementation of therapeutic interventions,” Dr. Romero said. “The PRB, Wayne State University and the Detroit Medical Center have created a unique partnership to study the biome of pregnancy and how it is altered in premature labor. This promising initiative will support a new knowledge-based economy in Detroit.”

Dr. Romero recognized the exceptional vision of WSU President M. Roy Wilson, the University’s Board of Governors, WSU School of Medicine Dean Valerie M. Parisi, M.D., M.P.H., M.B.A.; the leadership of the DMC; and the city of Detroit for “making possible many of the discoveries described on the pages of Science, for much of this work has taken place in Detroit.”

Dr. Greenwald provides effective model for sustained-release drug to fight opioid addiction
In Headlines on August 13, 2014
Mark Greenwald, Ph.D.

Mark Greenwald, Ph.D.

An important new study conducted by a Wayne State University School of Medicine professor and global research and development team leaders at Reckitt Benkiser Pharmaceuticals provides new insight into the long-acting effects of a drug and its sustained-release system that has the potential to become an effective treatment of opioid dependence by improving medication adherence and reducing the diversion, abuse and unintended exposure associated with conventional treatments.

The study, “A Population Pharmacokinetic and Pharmacodynamic Modelling Approach to Support the Clinical Development of RBP-6000, a New, Subcutaneously Injectable, Long-Acting, Sustained-Release Formulation of Buprenorphine, for the Treatment of Opioid Dependence,” published in the highly ranked journal Clinical Pharmacokinetics, details the long-acting profile of RBP-6000, a form of the drug Buprenorphine.

“This type of comprehensive, empirically-based modeling has never been explicitly done before with any substance abuse medication, and is among the first in the entire psychiatric field,” said Mark Greenwald, Ph.D., professor of psychiatry and behavioral neurosciences for the WSU School of Medicine, author of the study. “This accomplishment exemplifies the tremendous opportunities for productive scientific collaboration between academic and industry partners, which are intended to benefit patients worldwide. Given the high prevalence and public health burden of opioid use disorder, there is a pressing need to expand safe and effective treatment options for motivated individuals.”

Society pays a high cost for opioid addiction, Dr. Greenwald said. The use of opioids in the United States has increased “tremendously” in the last 10 years, from 174 million users in 2000 to 257 million users in 2009. The widespread availability and variety of prescription opioid analgesic products, coupled with changes in treatment practices, has helped feed the increase in dependence upon the drugs.

Studies have estimated that between 2.2 million and 2.4 million Americans begin non-medical use of opioids annually. Non-medical use of these drugs now exceeds the use of many street drugs, including cocaine and heroin. Overdose deaths from prescription drugs have exceeded deaths attributed to street drugs since 2002 and have surpassed traffic accidents as a cause of accidental death. In 2011, more than 1,252,500 of 2.5 million emergency room visits associated with drug abuse or addiction involved illicit drugs, including heroin and narcotic pain relievers.

In this unprecedented study, the team developed a pharmacokinetic/pharmacodynamic model to predict relationships between plasma concentrations and levels of mu opioid receptor binding during buprenorphine treatment, and how these biological indices predict the drug’s clinically important pharmacodynamic effects to promote drug abstinence. This, in turn, has proven essential to facilitating the ongoing clinical development of a monthly subcutaneous “depot treatment” for opioid use disorder of the drug RBP-6000. Buprenorphine enables addicts to discontinue opioids without experiencing withdrawal symptoms. It carries a lower risk of abuse and addiction compared to full opioids.

The comprehensive model is the first study, Dr. Greenwald said, to combine clinical molecular neuroimaging, and plasma concentration and pharmacodynamics data to predict effective dosing levels for the novel formulation of a therapy for addiction. The monthly RBP-6000 sustained-release treatment could offer advantages over current buprenorphine therapy by improving patients’ medication adherence.

This highly innovative work evolved from Dr. Greenwald's National Institute on Drug Abuse-funded landmark positron emission tomography, pharmacokinetic and pharmacodynamic studies with sublingual buprenorphine tablets, which have contributed to improving physician training with the Food and Drug Administration-approved Buprenorphine medication.

Pharmacokinetic/pharmacodynamic modeling predicts the effect and efficacy of drug dosing, studying how the body absorbs, distributes and metabolizes a drug over time. Such models are crucial to designing further research and clinical trials.

Dr. Greenwald has previously served as a paid consultant to Reckitt Benkiser Pharmaceuticals, but not in relation to this study or its publication.

Older Articles