Science Weekly podcast: Middle-aged brains and information overload

Filed Under Uncategorized | Comments Off on Science Weekly podcast: Middle-aged brains and information overload

New York Times science editor Barbara Strauch describes the surprising abilities of a middle-aged mind; James Gleick on information overload; plus, the latest in our series of unanswerable questions

BioMed Israel in May and the DIA Annual Meeting in June


Dr. Jules T. Mitchel of Target Health will be at BioMed, Israel (May 23-25 in Tel Aviv). Please let us know if you will be attending Target Health currently has 15 Israeli clients with some extraordinary products and a client base that is growing.


The annual DIA meeting will be held in Chicago this year (June 20-23). We will again be facing the Food Court so we will be easy to find. At DIA we will be showing off our software suite for the “paperless clinical trial.” You will be impressed and the price is right. Please let us know if you will be attending.


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:

Injectable Gel Could Spell Relief for Arthritis Sufferers


New gel (red, with yellow rectangles representing encapsulated medicine) is injected into an
arthritic joint. There, enzymes (black image) associated with arthritis, break down the
biodegradable gel, releasing the medicine. (Credit: Praveen Vemula, Karp lab, BWH)




Some 25 million people in the US suffer from rheumatoid arthritis or 1) ___, diseases characterized by often debilitating joint pain. Now, researchers at Brigham and Women’s Hospital (BWH) report an injectable gel that could spell the future for treating these diseases. Among its advantages, the gel could allow the targeted release of medicine at an affected 2) ___, and could dispense that medicine on demand in response to enzymes associated with arthritic flare-ups.


“We think that this platform could be useful for multiple medical applications including the localized treatment of cancer, ocular disease, and cardiovascular disease,” said Jeffrey Karp, leader of the research and co-director of the Center for Regenerative Therapeutics at BWH. Karp presented the findings April 15 at the annual meeting of the Society for Biomaterials (SFB) as part of winning the coveted SFB Young Investigator Award for this work. The work was also reported by Karp and colleagues in the May 2011 issue of the Journal of Biomedical Materials Research (JBMR): Part A.

Local Delivery: Arthritis is a good example of a disease that attacks specific parts of the 3) ___. Conventional treatments for it, however, largely involve drugs taken orally. Not only do these take a while (often weeks) to exert their effects, they can have side effects. One reason is that oral drugs are dispersed throughout the body, not just at the affected joint. Further, high concentrations of the drug are necessary to deliver enough to the affected joint, which runs the risk of 4) ___toxicity. “There are many instances where we would like to deliver 4) ___ to a specific location, but it’s very challenging to do so without encountering major barriers,” says Karp, who also holds appointments through Harvard Medical School (HMS), Harvard Stem Cell Institute (HSCI), and the Harvard-MIT Division of Health Sciences and Technology (HST). For example, you could inject a drug into the target area, but it won’t last long – only minutes to hours – because it is removed by the body’s highly efficient 5) ___ system.


Toward the Holy Grail: “The Holy Grail of drug delivery is an autonomous system that [meters] the amount of drug released in response to a biological 6) ___, ensuring that the drug is released only when needed at a therapeutically relevant concentration,” wrote Karp. The research team tackled the problem by first determining the key criteria for a successful locally administered arthritis treatment. In addition to having the ability to release drug on demand, for example, the delivery vehicle should be injectable through a small 7) ___ and allow high concentrations of the drug. The team ultimately determined that an injectable gel seemed most promising.


Next Step: To cut the time involved in bringing a new technology to market, the team focused only on materials already designated by the FDA as being generally recognized as safe (GRAS) for use in 8) ___. Ultimately, they discovered a GRAS material that could be coaxed into self-assembling into a drug-containing 9) ___. They further expected that the same material would disassemble, releasing its drug payload, when exposed to the enzymes present during inflammations like those associated with 10) ___.


Promising Results: A series of experiments confirmed this. For example, the team created a gel containing a dye as a stand-in for a drug, then exposed it to 11) ___ associated with arthritis. The drug was released. Further, the addition of agents that inhibited the enzymes stopped the release, indicating that the gel can release encapsulated agents in an on-demand manner. Although the team has yet to test this in humans, they did find that 12) ___ was also released in response to synovial fluid taken from arthritic human joints. Among other promising results, the researchers found that gel injected into the 13) ___ joints of mice remained stable for at least two months. Further, the gel withstood wear and tear representative of conditions in a moving joint.

ANSWERS: 1) osteoarthritis; 2) joint; 3) body; 4) drugs; 5) lymphatic; 6) stimulus; 7) needle; 8) humans; 9) gel; 10) arthritis; 11) enzymes; 12) dye; 13) healthy




Antique Medical Posters in Art Exhibit, Health for Sale




A new exhibit at the Philadelphia Museum of Art (April 2 – July 31) celebrates the slick design of old public health messages and pharmaceutical ads. “The Gross Clinic” by Thomas Eakins, is opening a new exhibition of posters called Health for Sale, with Medical Posters from 1846 to Present


Franz von Stuck, the creator of this poster for an international hygiene fair, was as well known for his graphic design as he was for his painting and sculpture. Many artist of the late 19th century were trained in graphic design and illustration in addition to the fine arts, so that they could earn a living as they began their careers.


1874: Compagnie de Fermiere’s mineral water Philadelphia Museum of Art


Franz von Stuck 1911: Philadelphia Museum of Art


The collection includes works depicting the “social plague” of syphilis, the benefits of aspirin, and the dangers of marijuana — the “Weed with Roots in Hell.” The posters in the exhibit were collected by William H. Helfand, a chemical engineer who worked for more than 30 years as an executive in pharmaceutical giant Merck’s international operations division. His job with Merck took him to Paris, where he collected numerous medical posters. Aside from medical posters, he has collected thousands of items, such as labels from pharmaceutical bottles, postcards, and medical pamphlets. The posters – ranging from those commissioned by wealthy pharmacists of the 1840s to ones with a more modern message, such as the poster from an 1985 concert to raise money for AIDS research. Many of the historical posters make dubious claims as to a medical product’s health effects. Some of the cures promise to do everything, but clearly they could not cure even the common cold.


The prints add to the museum’s Ars Medica collection, which includes Rembrandt etchings of well known doctors of the 19th century. Many artist of the late 19th century were trained in graphic design and illustration in addition to the fine arts, so that they could earn a living as they began their careers, says Ittman. Philadelphia, in particular, was a magnet for graphic designers who then went on to become major artists, he notes.




Old Man in Red Night Shirt


This 1910 poster by Franz von Stuck depicts an old man jumping for joy because the drug he’s taken has cured him of rheumatism, arthritis, gout and kidney stones. Although the product is French, it is written for and promoted to the Spanish market.

Coughing Bears

James Ayer owned an apothecary in Lowell, Massachusetts in the mid 19th century, selling cures such as the Cherry Pectoral cough syrup pictured here, as well as Sarsaparilla extract for a variety of maladies, from syphilis to psoriasis to cancer.









Arranged thematically, the works range in date from an 1846-47 poster advertising quinine “bitters” recommended for treating dyspepsia, to a 1985 poster promoting a benefit concert to raise money for AIDS research. Helfand’s passion took him from the Print Club on Latimer Street in Philadelphia, to New York print shops, to the rue de Seine in Paris, where he found many of the posters now in his collection. One of the most striking images is Man as Industrial Palace, a diagram of the human body as an industrial factory, dreamed up in the 1920s in Germany by Dr. Fritz Kahn. To capture the attention of the public, medical posters frequently featured whimsical subject matter such as bears drinking Ayer’s Cherry Pectoral. These engaging graphics were often the work of anonymous designers, but prominent artists such as Jules Cheret (French, 1836–1932) and Leonetto Cappiello (French, born Italy, 1875–1942) also produced medical posters. It was Cheret’s large, colorful lithographs that elevated the crude commercial placard to the rank of fine art in the 1890s, with depictions of vivacious young French women (modeled after his own wife) that call to mind the popular American “Gibson Girl” of the early 20th century.


Other medically themed posters offered a more serious message, such as those that warned about deadly diseases. These were often endorsed and disseminated in government service campaigns, and spared no detail in graphically conveying the potential danger. Posters of this type ranged from admonishments about amoral behavior (an anti-alcohol campaign from 1902-12), to drug use (Marihuana, Weed with Roots in Hell, c. 1936), to an even more serious campaign of the 1930s against syphilis that warned, “Syphilis is a social plague; its victims are beyond number.”Most of the posters in the exhibition advertised products that have long since disappeared.


The Museum’s Ars Medica Collection was launched in 1949 with support from the Philadelphia-based pharmaceutical company Smith, Kline & French Laboratories (now GlaxoSmithKline), which continued to support the collection’s growth for four decades. Comprised of prints, drawings, photographs, posters, illustrated books, and ephemera covering a broad array of medical topics, it now includes some 3,000 works of art on paper and is the only collection of its type housed in a major art museum.


Health advice to American GIs During WW2 Brain Salt Headaches Humor Medicine, 1890


This poster was part of the tuberculosis education campaign started by the American Red Cross. Every year, the Red Cross would commission stamps to benefit the study and prevention of tuberculosis. The stamp, pictured in the lower left corner of the poster, depicts a Santa Claus holding a sack marked with a red cross.

Cause and New Treatment for Common Recurrent Fever in Children Identified


A syndrome called periodic fever associated with aphthous stomatitis, pharyngitis and cervical adenitis – or PFAPA, is characterized by monthly flare-ups of fever, accompanied by sore throat, swollen glands and mouth lesions. Children with PFAPA syndrome experience attacks of fever, each lasting three to six days, usually three to eight weeks apart. Their predictability is so regular that parents have been known to make pediatric appointments a week ahead of when they expect their child to experience a PFAPA episode. Affected children experience their first attack before the age of 5, with fever episodes usually abating in adolescence or young adulthood. While the only remedy for PFAPA, besides corticosteroids, is removal of an affected child’s tonsils, which has a good rate of success in eliminating PFAPA syndrome, but is an invasive alternative.


According to a study published in the early online edition of the Proceedings of the National Academy of Sciences (8 April 2011), has identified a promising new treatment in children for the most common periodic fever disease in children. The proposed treatment, which will be validated in a larger study before it is recommended in treating PFAPA syndrome, wards off an inappropriate immune system attack without increasing the frequency of flare-ups, a problem caused by the current standard treatment with corticosteroids.


“Until now, the basis of PFAPA has been a mystery,” said senior author and NHGRI Scientific Director Daniel Kastner, M.D., Ph.D. “Advances in genomic analysis have allowed us to define a major role for the innate immune system, the body’s first line of defense against infection. Targeting a specific product of white blood cells at the first sign of fever appears to abort the attacks.”


The new experimental treatment resulted from the authors using a systems biology approach, which entailed gene and protein expression and cell biology analysis in carefully selected patient and healthy control subjects, to determine the underlying disturbance of the immune system. They analyzed patient blood samples to detect which gene and protein networks are involved in the cell signaling and metabolic pathways activated in the disease. The study evaluated 21 patients with PFAPA syndrome along with an equal number of healthy children and 12 children with a distinctly different set of hereditary fever syndromes. They analyzed gene expression during episodes of fever and intervening periods when the children were well. The analysis revealed gene expression profiles that uniquely identified PFAPA immune response.


During PFAPA flare ups, the authors detected activation of both forms of immune response: 1) the innate, first-line-of-defense immunity, and 2) adaptive immunity, which is the body’s ability to detect and remember an infection in order to fight it later. This dual response supports the idea that the fevers of PFAPA are an immunologic response to some external stimulus, possibly related to microbial infection.


The authors looked for biological markers that would indicate the onset of a flare-up of fever in children with PFAPA. During PFAPA flare-ups, the authors detected decreased numbers of activated T cells, white blood cells that play a role in the cell’s innate immune response. They suspect that these activated T cells migrated to the lymph nodes in the neck, where they accumulate. They also detected over-expression of genes activated in innate immune responses, including interleukin-1, a molecule that is important in triggering fever and inflammation.


From these data, the researchers hypothesized that anakinra, a drug that prevents interleukin-1 from binding to its receptor, could be therapeutic. They administered anakinra by injection to five children on the second day of their PFAPA fevers and all showed a reduction in fever and inflammatory symptoms within hours.


“The anakinra treatment has the potential to restore these children to a mostly symptom-free childhood,” said Dr. Kastner. “The comprehensive analysis of gene expression during PFAPA attacks would not have been possible without the tools created by the Human Genome Project, and the possibility of an effective treatment is yet another of the genome project’s many dividends.”


A larger clinical trial for the use of anakinra in treating this periodic fever syndrome is planned, Dr. Kastner said.

Distribution of Cancers in the HIV/AIDS Population Is Shifting


As treatments for HIV/AIDS improve and patients are living longer, the distribution of cancers in this population has undergone a dramatic shift in the US. While cases of the types of cancer that have been associated with AIDS progression have decreased, cases of other types of cancer are on the rise. These results were published online April 11, 2011, in the Journal of the National Cancer Institute (


People with HIV infection are known to be at increased risk for certain cancers not classified as AIDS-defining malignancies. Of these, the most common are anal, lung, and liver cancers, and Hodgkin lymphoma. Higher risks for these four malignancies stems from co-infections such as human papillomavirus (HPV), hepatitis B and C viruses, and Epstein-Barr virus, as well as higher smoking rates in the HIV/AIDS population. These four non-AIDS-defining malignancies made up nearly half of all cancers diagnosed in this population from 2001 through 2005. These cancers increased dramatically over the 15 years; there were eight times more anal cancer, double the number of lung cancers and Hodgkin lymphomas, and five times as many liver cancers in 2001 through 2005 as compared to 1991 through 1995.


The CDC uses the presence of certain diseases, including three cancers – Kaposi sarcoma, non-Hodgkin lymphoma, and invasive cervical cancer – as part of the criteria to determine whether an HIV-infected person has developed AIDS. The introduction of highly active antiretroviral therapy (HAART) in 1996 resulted in improved immune function, reduced risk of AIDS progression, and greatly improved survival for people infected with HIV. As a result, cases of those AIDS-defining cancers decreased threefold, from 34,000 cases between 1991 and 1995 to about 10,000 cases between 2001 and 2005. In contrast, the total number of all other cancers tripled, from around 3,000 in the earlier period to 10,000 in the latter period. Since 2003, annual counts of these other cancers in the HIV/AIDS population have exceeded the number of AIDS-defining malignancies.


The study observed striking increases for a number of malignancies related to cancer risk factors that are known to be prevalent in this population, such as smoking and infection with cancer-causing viruses. They also observed increases for nearly all other cancers, which is what one might expect for an aging population.


The increase in non-AIDS defining malignancies from 1991 through 2005 reflects a quadrupling of the number of people in the United States living with AIDS, and a substantial age shift in this population due to an increase in people age 40 and over. Since cancer typically occurs at older ages, an increase in incidence would be expected as the HIV/AIDS population grows older.

Presurgical Stress Management Improves Postoperative Immune Function in Men With Prostate Cancer Undergoing Radical Prostatectomy


A study, published in Psychosomatic Medicine (2011;73: 218-225), was performed to assess whether stress management (SM) improved immune outcomes in men undergoing surgery for prostate cancer.


For the study, a total of 159 men were assigned randomly to a two-session presurgical SM intervention, a two-session supportive attention (SA) group, or a standard care (SC) group. Men in the SM group discussed their concerns about the upcoming surgery and were taught diaphragmatic breathing, guided imagery; they had an imaginal exposure to the day of surgery and learned adaptive coping skills. Men in the SA group discussed their concerns about the upcoming surgery and had a semistructured medical interview. Blood samples were collected at baseline (1 month before surgery) and 48 hours after surgery. Measures of mood (Profile of Mood States) were collected at baseline, 1 week pre surgery, and the morning of surgery.


Results showed that men in the SM group had significantly higher levels of natural killer cell cytotoxicity (p = 0.04), and higher levels of circulating proinflammatory cytokines (interleukin [IL]-12p70, p = 0.02; IL-1beta, p = 0.02; and tumor necrosis factor-alpha, p = 0.05) 48 hours post surgery than men in the SA group.


In addition, the SM group had higher levels of natural killer cell cytotoxicity (p = 0.02) and IL-1beta (p = 0.05) than men in the SC group.


Immune parameters increased for the SM group and decreased or stayed the same for the SA and SC groups. The SM group had significantly lower Profile of Mood States scores than the SC group (p = .006), with no other group differences between SA and SC groups. Changes in mood were not associated with immune outcomes.


According to the authors, the finding that SM leads to decreased presurgical mood-disturbance and increased immune parameters after surgery reveals the potential psychological and biological benefits of presurgical SM.

TARGET HEALTH excels in Regulatory Affairs and Public Policy issues. Each week we highlight new information in these challenging areas.



FDA Warns Public of Continued Extortion Scam by FDA Impersonators


The FDA has warned the public about criminals posing as FDA special agents and other law enforcement personnel as part of a continued international extortion scam. The criminals call the victims – who in most cases previously purchased drugs over the Internet or via “telepharmacies” – and identify themselves as FDA special agents or other law enforcement officials. The criminals inform the victims that purchasing drugs over the Internet or the telephone is illegal, and that law enforcement action will be pursued unless a fine or fee ranging from $100 to $250,000 is paid. Victims often also have fraudulent transactions placed against their credit cards. The criminals always request the money be sent by wire transfer to a designated location, usually in the Dominican Republic. If victims refuse to send money, they are often threatened with a search of their property, arrest, deportation, physical harm and/or incarceration.


“Impersonating an FDA official is a violation of federal law,” said Dara Corrigan, the FDA’s associate commissioner for regulatory affairs. “FDA special agents and other law enforcement officials are not authorized to impose or collect criminal fines. Only a court can take such action.”


In most instances, victims of extortion-related calls have also received telephone solicitations for additional pharmaceutical purchases from other possibly related, illegal entities located overseas. The extortionists use customer lists complete with extensive personal information provided through previous purchase transactions. These include names, addresses, telephone numbers, Social Security numbers, dates of birth, purchase histories and credit card account numbers. Typically, these criminals use telephone numbers that change constantly and make it appear as though their calls originate in the United States. No known victim has been approached in person by a law enforcement impersonator associated with this scheme.


The FDA’s Office of Criminal Investigations, with the U.S. Drug Enforcement Administration, and the U.S. Immigrations and Customs Enforcement, Homeland Security Investigations, with the support of various U.S. Attorneys, are pursuing multiple national and international criminal investigations. Arrests have been made and additional prosecutions are pending; however, the scheme is likely to continue.


Victims of this scheme who have suffered monetary loss through the payment of funds in response to an extortion call from a person purporting to be an FDA or other law enforcement official regarding illegal pharmaceutical transactions may obtain a victim questionnaire by contacting the FDA’s Office of Criminal Investigations and clicking “Report Suspected Criminal Activity.”


The FDA also reminds consumers that pharmaceutical products offered online and by telephone by sources of unknown origin can pose a substantial health risk. Products recovered during this investigation that were purchased from online or telephone sources have been found to contain trace amounts of heroin, other undisclosed and potentially harmful active pharmaceutical ingredients, or no active ingredient at all. Purchases should only be made from licensed pharmacies located in the United States. In addition to the increased risk of purchasing unsafe and ineffective drugs from Web sites operating outside the law, personal data may be compromised.


For more on unlawful drug sales on the Internet, see Protecting Yourself.


For more information about our expertise in Medical Affairs, contact Dr. Mark L. Horn. For Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.