Science Weekly podcast: What is ‘the self’ and where exactly is it?

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We attempt to explain ‘the self’ with Julian Baggini; Tim Flannery tells us how love can save the environment; and Brian Cox answers the ‘Hannaford question’



Elsevier Business Intelligence eSource Webinar Presented by Dr. Jules T. Mitchel, President, Target Health


On April 12, 2011 at 1 pm EDT, Dr. Jules Mitchel, President of Target Health Inc., will present a webinar entitled: New eSource Documentation Guidance: Ensuring Quality, Integrity and Traceability.


The webinar, sponsored by Elsevier Business Intelligence, will detail initial steps to achieve a compliant paperless clinical trial. Dr. Mitchel will also focus on the impact of the draft FDA guidance entitled Electronic Source Documentation in Clinical Investigations on sponsors and those who provide monitoring, data management and EDC services.


During this webinar, you will learn:


  • The FDA perspective on what is a source record
  • How FDA has opened the door to direct data entry:
  • How to be compliant
  • How to address the impact of direct data entry as well as the electronic health/medical record (EHR/EMR) in clinical research operations and data management


Dr. Mitchel will also answer questions in the Q&A session.


To register, go to


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. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health website at:


Soy Increases Radiation’s Ability to Kill Lung Cancer Cells

Soybean Plant



A component in soybeans increases radiation’s ability to kill lung cancer 1) ___, according to a study published in the April issue of the Journal of Thoracic Oncology, the official monthly journal of the International Association for the Study of Lung Cancer. “To improve radiotherapy for lung cancer cells, we are studying the potential of natural non-toxic components of soybeans, called soy isoflavones, to augment the effect of radiation against the 2) ___ cells and at the same time protect normal lung against radiation injury,“ said Dr. Gilda Hillman, an associate professor in the Department of Radiation Oncology at Wayne State University’s School of Medicine and the Karmanos Cancer Institute in Detroit.


“These natural soy isoflavones can sensitize cancer cells to the effects of 3) ___, by inhibiting survival mechanisms which cancer cells activate to protect themselves,“ Hillman said. “At the same time, soy isoflavones can also act as 4) ___ in normal tissues, which protect them against unintended damage from the radiotherapy. In a recent study, published in the Journal of Thoracic Oncology, we demonstrated that soy isoflavones increase killing of 5) ___ cells by radiation via blocking DNA repair mechanisms, which are turned on by the cancer cells to survive the damage caused by radiation.“


Human A549 non-small cell lung cancer (NSCLC) cells that were treated with soy 6) ___ before radiation showed more DNA damage and less repair activity than cells that received only radiation. Researchers used a formulation consisting of the three main isoflavones found in soybeans, including genistein, daidzein and glycitein. Previously, it was found that pure genistein demonstrated antitumor activity in human NSCLC cell lines and enhanced the effects of EGFR-tyrosine kinase inhibitors. This study showed that the soy mixture had an even greater 7) ___ effect than pure genistein. The soy mixture also is consistent with the soy isoflavone pills used in clinical studies, which have been proven to be 8) ___.

ANSWERS: 1) cells; 2) tumor; 3) radiotherapy; 4) antioxidants; 5) cancer; 6) isoflavones; 7) antitumor; 8) safe




Chronic Obstructive Pulmonary Disease (COPD)

Pathologic Features of Chronic Obstructive Pulmonary Disease
Anatomic varieties of emphysema. A. Centriacinar (centrilobular). B . Paraseptal (distal acinar). C .Panacinar (panlobular). D. Irregular (scar). The dashed lines mark the edge of the acinus. Only centriacinar and panacinar emphysema are commonly observed in COPD.



The word emphysema is derived from Greek and means “to blow into,“ hence “air-containing“ or “inflated.“ COPD has probably always existed but has been called by different names in the past. Bonet described a condition of “voluminous lungs“ in 1679. In 1769, Giovanni Morgagni described 19 cases where the lungs were “turgid“ particularly from air. The first description and illustration of the enlarged airspaces in emphysema was provided by Ruysh in 1721.


Matthew Baillie illustrated an emphysematous lung in 1789 and described the destructive character of the condition. Badham used the word “catarrh“ to describe the cough and mucus hypersecretion of chronic bronchitis in 1814. He recognized that chronic bronchitis was a disabling disorder. Rene Laennec, the physician who invented the stethoscope, used the term emphysema in his book A Treatise on the Diseases of the Chest and of Mediate Auscultation (1837), to describe lungs that did not collapse when he opened the chest during an autopsy. He noted that they did not collapse as usual because they were full of air and the airways were filled with mucus.


In 1842, John Hutchinson invented the spirometer, which allowed the measurement of vital capacity of the lungs. However, his spirometer could only measure volume, not airflow. Tiffeneau in 1947 and Gaensler in 1950 and 1951 described the principles of measuring airflow. The foundation of modern knowledge of the pathologic anatomy of pulmonary emphysema was laid by J. Gough in 1952 when he described centrilobular emphysema and distinguished it from panlobular emphysema. The paper section technique developed by Gough and Wentworth was largely responsible for this advance, as it made examinations of sections of entire inflated lungs possible and simple.  A comprehensive microscopic description of emphysema was then provided by McLean, who demonstrated the relationship of destruction to inflammatory alterations of the bronchioles, and also discussed alterations of the vasculature.


The terms chronic bronchitis and emphysema were formally defined at the CIBA guest symposium of physicians in 1959. The term COPD was first used by William Briscoe in 1965 and has gradually overtaken other terms to become established today as the preferred name for this disease.




Hydrocortisone Therapy for Patients with Multiple Trauma



In cases of marked stress, such as during surgery or during illnesses with high fever, if the body cannot make enough hydrocortisone, there may be a need to take extra doses of this steroid medication to avoid severe consequences. However, the role of stress-dose hydrocortisone in the management of trauma patients is currently unknown.


As a result, a study published in the Journal of the American Medical Association (2011;305:1201-1209), was performed to test the efficacy of hydrocortisone therapy in trauma patients.


The investigation was a multicenter, randomized, double-blind, placebo-controlled HYPOLYTE (Hydrocortisone Polytraumatise) study and included 150 patients with severe trauma. For the study, patients were randomly assigned to a continuous intravenous infusion of either hydrocortisone (200 mg/d for 5 days, followed by 100 mg on day 6 and 50 mg on day 7) or placebo. The treatment was stopped if patients had an appropriate adrenal response. The main outcome measure was hospital-acquired pneumonia within 28 days. Secondary outcomes included the duration of mechanical ventilation, hyponatremia, and death.


An intention-to-treat (ITT) analysis included 149 patients, and a modified ITT analysis included 113 patients with corticosteroid insufficiency. In the ITT analysis, 35.6% treated with hydrocortisone and 51.3% receiving placebo developed hospital-acquired pneumonia by day 28 (hazard ratio [HR], 0.51; P = .007). In the modified ITT analysis, 35.7% in the hydrocortisone group and 54.4% in the placebo group developed hospital-acquired pneumonia by day 28 (HR, 0.47; P = .01). Mechanical ventilation-free days increased with hydrocortisone by 4 days (P = .001) in the ITT analysis and 6 days (P < .001) in the modified ITT analysis. Hyponatremia was observed in 9.2% in the placebo group vs none in the hydrocortisone group (P = .01). Four of 76 patients (5.3%) in the placebo group and 6 of 73 (8.2%) in the hydrocortisone group died (P = .44).


According to the authors, in intubated trauma patients, the use of an intravenous stress-dose of hydrocortisone, compared with placebo, resulted in a decreased risk of hospital-acquired pneumonia.

AAV2-GAD Gene Therapy for Advanced Parkinson’s Disease: A Double-Blind, Sham-Surgery Controlled, Randomized Trial

Gene transfer of glutamic acid decarboxylase (GAD) and other methods that modulate production of GABA in the subthalamic nucleus improve basal ganglia function in parkinsonism in animal models. According to a study published online in The Lancet (17 March 2011), a study was performed to assess the effect of bilateral delivery of AAV2-GAD in the subthalamic nucleus compared with sham surgery in patients with advanced Parkinson’s disease (PD).

For the study, patients aged 30-75 years who had progressive levodopa-responsive PD and an overnight off-medication unified PD rating scale (UPDRS) motor score of 25 or more were enrolled into a double-blind, phase 2, randomized controlled trial. The primary outcome measure was the 6-month change from baseline in double-blind assessment of off-medication UPDRS motor scores. Infusion failure or catheter tip location beyond a predefined target zone led to exclusion of patients before unmasking for the efficacy analysis.

Of 66 patients assessed for eligibility, 23 were randomly assigned to sham surgery and 22 to AAV2-GAD infusions. Of those, 21 and 16, respectively, were analyzed. At the 6-month endpoint, UPDRS score for the AAV2-GAD group decreased by 8?1 points (p<0?0001) and by 4?7 points in the sham group (p=0?003). The AAV2-GAD group showed a significantly greater improvement from baseline in UPDRS scores compared with the sham group over the 6-month course of the study (p=0?04). One serious adverse event occurred within 6 months of surgery; this case of bowel obstruction occurred in the AAV2-GAD group, was not attributed to treatment or the surgical procedure, and fully resolved. Other adverse events were mild or moderate, likely related to surgery and resolved.

According to the authors, the efficacy and safety of bilateral infusion of AAV2-GAD in the subthalamic nucleus supports its further development for PD and shows the promise for gene therapy for neurological disorders.



Weight Loss, Exercise, or Both and Physical Function in Obese Older Adults



Obesity exacerbates the age-related decline in physical function and causes frailty in older adults; however, the appropriate treatment for obese older adults is controversial. As a result, a 1-year, randomized, controlled study, published in the New England Journal of Medicine (2011; 364:1218-1229), evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese. Participants were randomly assigned to a control group, a weight-management (diet) group, an exercise group, or a weight-management-plus-exercise (diet-exercise) group. The primary outcome was the change in score on the modified Physical Performance Test. Secondary outcomes included other measures of frailty, body composition, bone mineral density, specific physical functions, and quality of life.

A total of 93 participants (87%) completed the study. In the intention-to-treat analysis, the score on the Physical Performance Test, in which higher scores indicate better physical status, increased more in the diet-exercise group than in the diet group or the exercise group (increases from baseline of 21% vs. 12% and 15%, respectively). The scores in all three of those groups increased more than the scores in the control group (in which the score increased by 1%; (P<0.001 for the between-group differences). Moreover, the peak oxygen consumption improved more in the diet-exercise group than in the diet group or the exercise group (increases of 17% vs. 10% and 8%, respectively; P<0.001). The score on the Functional Status Questionnaire, in which higher scores indicate better physical function, increased more in the diet-exercise group than in the diet group (increase of 10% vs. 4%, P<0.001).

Body weight decreased by 10% in the diet group and by 9% in the diet-exercise group, but did not decrease in the exercise group or the control group (P<0.001). Lean body mass and bone mineral density at the hip decreased less in the diet-exercise group than in the diet group (reductions of 3% and 1%, respectively, in the diet-exercise group vs. reductions of 5% and 3%, respectively, in the diet group; P<0.05 for both comparisons). Strength, balance, and gait improved consistently in the diet-exercise group (P<0.05 for all comparisons). Adverse events included a small number of exercise-associated musculoskeletal injuries.

According to the authors, the findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone.

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



FDA Statement on Makena for Preterm Birth



On February 3, 2011, the FDA approved the drug Makena (hydroxyprogesterone caproate) for the reduction of the risk of certain preterm births in women who have had at least one prior preterm birth. KV Pharmaceuticals, the drug’s owner, received considerable assistance from the federal government in connection with the development of Makena by relying on research funded by the National Institutes of Health to demonstrate the drug’s effectiveness. It also obtained seven years of exclusivity under the Orphan Drug Act, obtained approval under FDA’s accelerated approval program, and received expedited review.

For many years, a version of the active ingredient of Makena, which is a synthetic progestin, has been available to patients whose physicians requested the drug from a pharmacist who compounded the drug. Generally, FDA has exercised enforcement discretion with respect to most products made through traditional pharmacy compounding. This has included products made from the active ingredient in Makena, hydroxyprogesterone caproate.

Because Makena is a sterile injectable, where there is a risk of contamination, greater assurance of safety is provided by an approved product. However, under certain conditions, a licensed pharmacist may compound a drug product using ingredients that are components of FDA approved drugs if the compounding is for an identified individual patient based on a valid prescription for a compounded product that is necessary for that patient. FDA prioritizes enforcement actions related to compounded drugs using a risk-based approach, giving the highest enforcement priority to pharmacies that compound products that are causing harm or that amount to health fraud.

FDA understands that the manufacturer of Makena, KV Pharmaceuticals, has sent letters to pharmacists indicating that FDA will no longer exercise enforcement discretion with regard to compounded versions of Makena. This is not correct.

In order to support access to this important drug, at this time and under this unique situation, FDA does not intend to take enforcement action against pharmacies that compound hydroxyprogesterone caproate based on a valid prescription for an individually identified patient unless the compounded products are unsafe, of substandard quality, or are not being compounded in accordance with appropriate standards for compounding sterile products. As always, FDA may at any time revisit a decision to exercise enforcement discretion.

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.



Target Health ( is a full service eCRO with full-time staff dedicated to all aspects of drug and device development. Areas of expertise include Regulatory Affairs, comprising, but not limited to, IND (eCTD), IDE, NDA (eCTD), BLA (eCTD), PMA (eCopy) and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, EDC utilizing Target e*CRF®, and Medical Writing.



Target Health has developed a full suite of eClinical Trial software including:


1) Target e*CRF® (EDC plus randomization and batch edit checks)

2) Target e*CTMS™

3) Target Document®

4) Target Encoder®

5) Target Newsletter®

6) Target e*CTR™ (electronic medical record for clinical trials).

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