Glen Park Selected as Review Editor of Frontiers in Pharmaceutical Medicine and Outcomes Research



We are pleased to announce that in addition to  Sr. Director of Clinical Research and Regulatory Affairs at Target Health Inc.,  Dr. Glen Park, has accepted the position and the challenge to serve as Review Editor of Frontiers in Pharmaceutical Medicine and Outcomes Research. Frontiers aims to change the world of academic research publishing to ensure high quality peer-reviewing, equal opportunity to publish and read, drive integration across disciplines, provide a spectrum of services for researchers and research-related organizations, and systematically translate advanced research knowledge to increase public understanding. The Frontiers vision is a comprehensive full-service system for all entities concerned with academic research.


The “Frontiers in” journal series operates as open access journals and, therefore, adopts the standard open access business model where authors pay the Article Publishing Fees (APF) to allow anyone to read their article for free (author-pay/reader-free). Frontiers has successfully pioneered its equal-opportunity publishing model in the field of Neuroscience and now aims to offer this model to fields across all of academia. The vision of Frontiers is to build the complete Tree of Academia and create a single platform for integration across fields.


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at

New Way to Learn About and Potentially Block Traits in Harmful Pathogens


Electron micrograph of Chlamydia mutant bacteria inside of a cell. These particular mutant bacteria, colored red, are defective in secreting high levels of virulence proteins, seen here as the accumulating dark granules in between two bacterial membranes. (Credit: Bidong Nguyen, Duke Molecular Genetics and Microbiology)




Researchers at Duke University Medical Center have developed a new way to identify the genes of harmful 1) ___, particularly those that have been difficult to study in the laboratory. This new method uses chemicals to create mutant bacteria, followed by genomic sequencing to identify all mutations. By looking for common genes that were mutated in Chlamydia sharing a particular trait, the investigators were able to rapidly “zero in” on the genes responsible for that 2) ___. The approach is versatile and inexpensive enough that it could be applied to study a range of microorganisms, said Raphael Valdivia, PhD, an associate professor of molecular genetics and microbiology at Duke. “We were able to learn about 3) ___ that allow Chlamydia to flourish in their hosts without the traditional, lengthy process of domesticating the pathogen to accept recombinant DNA,” Valdivia said. “Our approach marries classical microbiology techniques with 21st century genome-4) ___ technologies. If you encounter a new dangerous microorganism and want to determine what genes are important, I think this represents an effective way to learn all we can, as fast as we can.” The work was published on Jan. 9 in the early edition of the Proceedings of the National Academy of Sciences.


One of the goals in studying microbial pathogens that harm 5) ___ and animals is to locate and disrupt the genes required for infection. The microbe in this study, Chlamydia, an STD which hides in human cells, and is a type of 6) ___ that must cause disease to be transmitted from one host to another. Chlamydia is the leading STD infection and a risk factor for pelvic inflammatory disease and infertility.


Prior to this work, the function of many 7) ___ genes had to be inferred by their similarity to genes from other bacteria. “By isolating mutants that don’t grow well inside cells and identifying the underlying mutations, we can learn a lot about how these genes contribute to disease,” Valdivia said. “These are the activities we’d like to block.” “For us, this significantly accelerates the analysis of Chlamydia and importantly, should be applicable to many other microbes that have been difficult manipulate with recombinant DNA approaches,” he said.


Valdivia suggested that even microbes associated with our normal intestinal flora, which are notoriously difficult to manipulate, are now open to exploration so that we can learn how their genes influence human health, including dietary disorders and inflammatory bowel 8) ___.


Valdivia also said that the new technique could help to create Chlamydia 9) ___ that have a combination of mutations that affect the pathogen’s virulence. “That way we can cripple some aspects of the bacterium’s ability to thrive intact in a host, while still allowing the bacterium to replicate enough to prime the immune 10) ___ against it.”


ANSWERS: 1) microbes; 2) trait; 3) genes; 4) sequencing; 5) humans; 6) bacteria; 7) Chlamydia; 8) disease; 9) vaccines; 10) system

King George III


King of Great Britain and Ireland later, King of the United Kingdom and of Hanover – Portrait by Allan Ramsay, 1762




George III (George William Frederick; 4 June 1738 – 29 January 1820) was King of Great Britain and King of Ireland from 25 October 1760 until the union of these two countries on 1 January 1801, after which he was King of the United Kingdom of Great Britain and Ireland until his death. George was the third British monarch of the House of Hanover, but unlike his two Hanoverian predecessors he was born in Britain, spoke English as his first language,and never visited Hanover.


His life and reign, which were longer than those of any previous British monarch, were marked by a series of military conflicts involving his kingdoms, much of the rest of Europe, and places farther afield in Africa, the Americas and Asia. Early in his reign, Great Britain defeated France in the Seven Years’ War, becoming the dominant European power in North America and India. However, many of its American colonies were soon lost in the American War of Independence. He played a minor role in the wars against revolutionary and Napoleonic France from 1793, which concluded in the defeat of Napoleon at the Battle of Waterloo in 1815.


George III was extremely popular in Britain.The British people admired him for his piety, and for remaining faithful to his wife.He was fond of his children, and was devastated at the death of two of his sons in infancy in 1782 and 1783 respectively.Nevertheless, he set his children a strict regimen. They were expected to attend rigorous lessons from seven in the morning, and to lead lives of religious observance and virtue.When his children strayed from George’s own principles of righteousness, as his sons did as young adults, he was dismayed and disappointed.


In the later part of his life, George III suffered from recurrent, and eventually permanent, mental illness. Medical practitioners were baffled by this at the time, although it has since been suggested that he suffered from the blood disease porphyria. Historical analysis of George III’s life has gone through a “kaleidoscope of changing views” that have depended heavily on the prejudices of his biographers and the sources available to them.Until re-assessment in the latter half of the 20th century, his reputation in America was one of a tyrant and in Britain he became “the scapegoat for the failure of imperialism”.He is often remembered as “The Mad King” and “The King Who Lost America”.


A study of samples of the King’s hair published in 2005 revealed high levels of arsenic, a possible trigger for the disease. The source of the arsenic is not known, but it could have been a component of medicines or cosmetics.The King may have suffered a brief episode of disease in 1765, but a longer episode began in the summer of 1788. At the end of the parliamentary session, he went to Cheltenham Spa to recuperate. It was the furthest he had ever been from London – just short of 100 miles (150 km) – but his condition worsened. In November, he became seriously deranged, sometimes speaking for many hours without pause, causing him to foam at the mouth and making his voice hoarse.With his doctors largely at a loss to explain his illness, spurious stories about his condition spread, such as the claim that he shook hands with a Plane (Sycamore) tree in the mistaken belief that it was the King of Prussia*.Treatment for mental illness was primitive by modern standards, and the King’s doctors, who included Francis Willis, treated the King by forcibly restraining him until he was calm, or applying caustic poultices to draw out “evil humors”


In late 1810, at the height of his popularitybut already virtually blind with cataracts and in pain from rheumatism, George III became dangerously ill. In his view the malady had been triggered by the stress he suffered at the death of his youngest and favorite daughter, Princess Amelia.By the end of 1811, George III had become permanently insane and lived in seclusion at Windsor Castle until his death at Windsor Castle on 29 January 1820.




*German composer, George Frederick Handel, who adopted England as his home, received a stipend from King George II and King George III.  In Handel’s great opera, Xerxes, the opening aria, “Ombra mai fu“, is sung by Persian (not Prussian) King, Xerxes to his Plane tree.


Handel – Xerxes – Ombra mai fu

By counter-tenor David Daniels, now singing in “The Enchanted island” at the MetOpera in NYC



32 Million Americans Have Autoantibodies That Target Their Own Tissues



The body’s immune system makes large numbers of proteins called antibodies to help the body fight off infections. In some cases, however, antibodies are produced that are directed against one’s own tissues. These are referred to as autoantibodies. Earlier studies have shown that antinuclear antibodies (ANA) can actually develop many years before the clinical appearance of autoimmune diseases, such as type 1 diabetes, lupus, and rheumatoid arthritis. ANA are frequently measured biomarkers for detecting autoimmune diseases, but the presence of autoantibodies does not necessarily mean a person will get an autoimmune disease. Other factors, including drugs, cancer, and infections, are also known to cause autoantibodies in some people.


According to an article published online in the journal Arthritis and Rheumatism (11 January 2012), more than 32 million people in the US have autoantibodies, which are proteins made by the immune system that target the body’s tissues and define a condition known as autoimmunity. The study looked at the prevalence of the most common type of autoantibody, known as ANA, and found that the frequency of ANA is highest among women, older individuals, and African-Americans. The study was conducted by the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health. Researchers in Gainesville at the University of Florida also participated.


According to the NIH, previous estimates of ANA prevalence have varied widely and were conducted in small studies not representative of the general population. Now, having this large data set that is representative of the general U.S. population which includes nearly 5,000 individuals, there is an accurate estimate of ANA and may allow new insights into the etiology of autoimmune diseases.


The study evaluated blood serum samples using a technique called immunofluorescence to detect ANA in 4,754 individuals from the 1994-2004 National Health and Nutrition Examination Survey (NHANES). The overall prevalence of ANA in the population was 13.8 percent, and was found to be modestly higher in African-Americans compared to whites. ANA generally increased with age and was higher in women than in men, with the female to male ratio peaking at 40-49 years of age and then declining in older age groups.


According to the authors, the peak of autoimmunity in females compared to males during the 40-49 age bracket is suggestive of the effects that the hormones estrogen and progesterone might be playing on the immune system. The study also found that the prevalence of ANA was lower in overweight and obese individuals than persons of normal weight. According to the authors, this raises the likelihood that fat tissues can secrete proteins that inhibit parts of the immune system and prevent the development of autoantibodies, but additional research is needed to understand the role that obesity might play in the development of autoimmune diseases.


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Genetic Abnormality Predicts Benefit from Treatment for a Rare Brain Tumor



Oligodendrogliomas, a form of brain tumor, are characterized by tumors that form in the nerve tissue of the brain. Oligodendrogliomas occur primarily in adults, and the average age at diagnosis is 35. The tumors comprise 9.4% of all primary brain and central nervous system tumors.


A clinical trial has shown that addition of chemotherapy to radiation therapy leads to a near doubling of median survival time in patients with oligodendroglioma that carries a chromosomal abnormality called the 1p19q co-deletion. This abnormality is characterized by the simultaneous deletion of the short arm of chromosome 1 and long arm of chromosome 19. The presence of the chromosomal abnormality was associated with substantially better prognosis and marked improvements in survival in a treatment program of combined chemotherapy and radiation therapy compared to radiation therapy alone.


In the trial, 286 patients with aggressive oligodendrogliomas were randomly assigned to study groups of equal size to receive radiotherapy alone or radiotherapy plus PCV chemotherapy, which includes the drugs procarbazine, lomustine and vincristine. Tumor tissue from all patients was collected and stored for genetic tests. The analysis was performed when about half of the patients had been followed for just over 11 years.


For the entire study population, the median overall survival time for patients receiving radiotherapy alone or radiotherapy plus PCV chemotherapy was similar. However, the 126 patients with 1p19q co-deleted tumors had much longer median survival times than the 135 patients whose tumors did not carry the 1p19q co-deletion: 8.7 years versus 2.7 years. This observation suggests that patients whose tumors contain the chromosomal abnormality will live substantially longer than patients whose tumors don’t carry it, regardless of treatment. Even more impressive, however, was the finding that 1p19q co-deletion predicted the benefit from adding chemotherapy to radiotherapy. Patients with 1p19q co-deleted tumors who received PCV chemotherapy plus radiotherapy (59 patients) had a median overall survival time of 14.7 years, compared with only 7.3 years for patients with co-deleted tumors who received radiotherapy alone (67 patients). Patients whose tumors did not have the chromosomal abnormality did not show an improvement in survival from the addition of chemotherapy.


The study, known as RTOG 9402, was led by the Radiation Therapy Oncology Group (RTOG) with the participation of the North Central Cancer Treatment Group, the National Cancer Institute of Canada Clinical Trials Group, the Eastern Cooperative Oncology Group, and SWOG (formerly the Southwest Oncology Group).

Prevalence of Obesity and Trends in the Distribution of Body Mass Index Among US Adults, 1999-2010



Between 1980 and 1999, the prevalence of adult obesity (body mass index [BMI] >30) increased in the United States and the distribution of BMI changed. More recent data suggested a slowing or leveling off of these trends. As a result, a study published online in the Journal of the American Medical Association (17 January 2012) was performed to estimate the prevalence of adult obesity from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) and compare adult obesity and the distribution of BMI with data from 1999-2008. NHANES includes measured heights and weights for 5,926 adult men and women from a nationally representative sample of the civilian non-institutionalized US population in 2009-2010 and for 22,847 men and women in 1999-2008.

The main outcome measures were the prevalence of obesity and mean BMI.


Results showed that in 2009-2010 the age-adjusted mean BMI was 28.7 for men and also 28.7 for women. The age-adjusted prevalence of obesity was 35.7% among adult men and 35.8% among adult women. Over the 12-year period from 1999 through 2010, obesity showed no significant increase among women overall (age- and race-adjusted annual change in odds ratio, 1.01; P=0.07), but increases were statistically significant for non-Hispanic black women (P =0.04) and Mexican American women (P =0.046). For men, there was a significant linear trend (1.04; P < .001) over the 12-year period. For both men and women, the most recent 2 years (2009-2010) did not differ significantly (P =0.08 for men and P = 0.24 for women) from the previous 6 years (2003-2008). Trends in BMI were similar to obesity trends.


According to the authors, in 2009-2010, the prevalence of obesity was 35.5% among adult men and 35.8% among adult women, with no significant change compared with 2003-2008.

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.



FDA Approves Voraxaze To Treat Patients With Toxic Methotrexate Levels



Methotrexate is a commonly used cancer chemotherapy drug normally eliminated from the body by the kidneys. However, patients receiving high doses of methotrexate may develop kidney failure.


The FDA approved Voraxaze (glucarpidase) to treat patients with toxic levels of methotrexate in their blood due to kidney failure. Voraxaze is an enzyme that rapidly reduces methotrexate levels by breaking the chemotherapy drug down to a form that can be eliminated from the body. Voraxaze is administered directly into a patient’s vein (intravenously).


Voraxaze has an orphan drug designation, given to therapies indicated for rare or specific disease populations. A single clinical study of 22 patients evaluated the effectiveness of Voraxaze. All patients received Voraxaze treatment. The study considered treatment a success if the methotrexate level fell below a critical level within 15 minutes and stayed below the critical level for eight days. Ten of the 22 patients achieved this standard. Although not all patients experienced this result, Voraxaze eliminated 95% of the methotrexate in all patients. A separate clinical study evaluated the safety of Voraxaze in 290 patients experiencing problems clearing methotrexate from their blood.


The most common side effects observed in greater than 1% of patients in the clinical study were low blood pressure (hypotension), headache, nausea, vomiting, flushing, and abnormal sensation (paraesthesia). Voraxaze is marketed by BTG International Inc., West Conshohocken, Pa.