Target Health is pleased to announce that our Chief Medical Officer (CMO), Dr. Mark L. Horn, will be the keynote speaker at the “e-Health Summit: Future Shock – What’s Next” conference being held on 20 May 2009 at The Conference Center at the New Jersey Hospital Association, 760 Alexander Road, Princeton, NJ 08543. The meeting will focus on the impact of the challenges in 1) making electronic record keeping a reality for practitioners, hospitals and clinical research; 2) the changing rules; and 3) the market implications of digitizing health records.

For more information about Target Health and any of our software tools for paperless clinical trials, please contact Dr. Jules T. Mitchel (212-681-2100 ext 0) or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website, and if you like the weekly newsletter, ON TARGET, you’ll love the Blog.

Why is the immune system able to fight off some viruses but not others, leading to chronic, life-threatening infections like HIV and 1) ___ C? A new UCLA AIDS Institute study suggests the answer lies in a protein called interleukin-21 (IL-21), a powerful molecule released by immune cells during chronic infection. Published May 7 in the online edition of Science, the finding could explain how the 2) ___ system limits viral replication, restricting a virus’s spread through the body. The researchers looked at two types of T-cells – CD4 T-cells and CD8 T-cells – each of which are immune cells that play an important role in the body’s response to infection. The CD4 T-cells help the immune system by producing IL-21 during chronic 3) ___, bolstering the CD8 T-cells’ ability to fight off the virus. The CD4 cells are the regulators – the generals. The CD8 cells go out and kill the invaders; they’re like the privates in the field. To shed light on how CD4 T-cells help their CD8 counterparts clear viruses, the researchers infected mice with one of two strains of a 4) ___. They knew that the first strain would generate a short-term infection and the second a chronic infection. The scientists tested each strain on two groups of mice. One group was normal and the other was bred without IL-21 5) ___ In the normal mice, the first strain elicited a strong T-cell response that completely eliminated the virus in 10 days. The second strain caused a chronic infection that exhausted the T-cells, hampering their ability to fight the virus. The UCLA team detected high levels of IL-21 in these mice, suggesting that the protein plays a crucial role in sustaining the T-cells’ ability to mount an immune response during long-lasting infection. When the scientists infected the mice that lacked IL-21 receptors with the chronic infection strain, something curious happened. The majority of virus-fighting CD8 T-cells disappeared, preventing the immune system from containing the spread of the virus. IL-21 fuels CD8 T-cells’ ability to function. These immune cells are running a long-distance race to contain the virus before it 6) ___. If they don’t get fed, they collapse on the track. Without IL-21, the CD8 T-cells dwindled, even when the CD4 T-cells produced a robust response. The result indicates that the T-cells rely on IL-21 to resolve persistent infection. After the immune system loses CD8 T-cells, it’s unable to clear the virus. This tells us that IL-21 is a critical player in the body’s fight against chronic infection. The study was funded by the UCLA Center for AIDS Research, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, and the National Institutes of Health. Brooks’ co-authors included Heidi Elsaesser of UCLA and Karsten Sauer of the Scripps Research Institute.

 

ANSWERS

 

1) hepatitis; 2) immune; 3) infection; 4) virus; 5) receptors; 6) spreads

The rod of Asclepius (sometimes also spelled Asklepios or Aesculapius), also known as the asklepian, is an ancient symbol associated with astrology, the Greek god Asclepius, and with healing. It consists of a single serpent entwined around a staff. The name of the symbol derives from its early and widespread association with Asclepius, the son of Apollo, who was a practitioner of medicine in ancient Greek mythology. The Rod of Asclepius also represents the constellation Ophiuchus (meaning “serpent-bearer”)), the thirteenth sign of the sidereal zodiac. The rod of Asclepius, is an older symbol than the medical caduceus, with two snakes wrapped around a winged staff. The one serpent and the staff appear to have been separate symbols that were combined at some point in the development of the Asclepian cult. The significance of the serpent has been interpreted in many ways. Sometimes the shedding of skin and renewal is emphasized as symbolizing rejuvenation, while other times the serpent is used as a symbol that unites and expresses the dual nature of the work of the physician, who deals with life and death, sickness and health. The ambiguity of the serpent as a symbol, and the contradictions it is thought to represent, are reflected in the meaning of the term pharmakon, which can mean “drug”, “medicine” and “poison” in ancient Greek. Products deriving from the bodies of snakes were known to have medicinal properties in ancient Greece, where at least some were aware that snake venom that might be fatal if it entered the bloodstream, could often be beneficial if taken orally. Snake venom appears to have been ‘prescribed’ in some cases as a form of therapy. One interpretation of the staff is that it is like the serpent, which conveys notions of resurrection and healing, while another (not necessarily incompatible) is that the staff was a walking stick associated with itinerant physicians. It has been claimed that the snake wrapped around the staff was a species of rat snake, Elaphe longissima. The two symbols were also associated with astrology. Asclepius was so skilled in the medical arts that he was reputed to have brought patients back from the dead. For this, he was punished and placed in the heavens as the constellation Ophiuchus, which lies between Sagittarius and Libra. In early Christianity, the constellation Ophiuchus was associated with Saint Paul holding the Maltese Viper. There are alternative theories accounting for the origin and development of the rod of Asclepius as a symbol. For example, a similar symbol, Nehushtan, is mentioned in the Bible. In Numbers 21:4-9 the Bible tells of the Israelites complaining to Moses and to God about their desperate situation. “Why have you brought us…to die in the wilderness? For there is no food and no water….” Numbers 21:5.  This angered God, and He sent fiery serpents that attacked the Israelites, and many died. The Israelites came to Moses with an appeal to God, repenting for their sin and asking forgiveness. God then spoke to Moses, telling him to make a bronze serpent set on a pole. Anyone who was bitten by one of the fiery serpents was to look at the bronze serpent and he or she immediately was healed. It has been suggested that the symbol of rod and snake, originated from a worm wrapped around a rod. Parasitic worms such as the “guinea worm” (Dracunculus medinensis) were common in ancient times, and were extracted from beneath the skin by winding them slowly around a stick. According to this theory, physicians might have advertised this common service by posting a sign depicting a worm on a rod. However plausible, no concrete evidence in support of this theory exists.

It is well-known that schizophrenia stems from complex interactions between multiple genes and environmental factors. Several candidate genes have recently been statistically linked to the illness in large genome-wide association studies. By regulating the flow of potassium ions into the cell, potassium channels control when neurons fire – electrically discharge and release a chemical messenger that signals neighboring neurons in a circuit. This flow is regulated, in part, by activity of the chemical messenger dopamine, the main target of antipsychotic medications used to treat schizophrenia. A recent study published in Nature Medicine (2009;15:509-518) has implicated a mechanism for schizophrenia that maintains the flow of potassium in cells. This new mechanism may provide a potential molecular target for new treatments. Results from the study showed that expression of a previously unknown form of a key potassium channel was found to be 2.5 fold higher than normal in the brain memory hub of people with schizophrenia and was linked to a hotspot of genetic variation. An extensive series of experiments suggested that selectively inhibiting this suspect form could help correct disorganized brain activity in schizophrenia, without risk of the cardiac side effects associated with some existing antipsychotic medications. One type of potassium channel, called KCNH2, has the potential role in sustaining the type of neuronal firing that supports the higher mental functions disturbed in schizophrenia. Spurred by hints from postmortem studies of genetic variation linked to schizophrenia in the genomic neighborhood of KCNH2, the research team analyzed the gene’s association with the illness in 5 independent samples comprising hundreds of families. This pinpointed 4 variations associated with schizophrenia within a small region of the KCNH2 gene. It was only then that the researcher team discovered a previously unknown version of KCNH2, called Isoform 3.1, that soared to levels 2.5 times higher-than-normal in the hippocampus (memory hub) of people who had schizophrenia – especially those with the risk-associated variations. Isoform 3.1 was also higher-than-normal in healthy individuals who carried the risk-associated variations. This signaled the existence of a risk-associated version of the KCNH2 gene. Very interesting, healthy controls carrying the risk gene version also: 

  1. Perform significantly worse-than-normal on measures of IQ and mental processing speed.
  2. Inefficiently process memory in the hippocampus and working memory in the prefrontal cortex, as revealed by functional MRI (magnetic resonance imaging) scans.
  3. Show significantly decreased volume in the hippocampus.

Effect of a Housing and Case Management Program on Emergency Department Visits and Hospitalizations Among Chronically Ill Homeless Adults

Homeless adults, especially those with chronic medical illnesses, are frequent users of costly medical services, especially emergency department and hospital services. As a result, a study published in the Journal of the American Medical Association (2009;301:1771-1778) was performed to assess the effectiveness of a case management and housing program in reducing use of urgent medical services among homeless adults with chronic medical illnesses. The investigation was a randomized controlled trial conducted at a public teaching hospital and a private, nonprofit hospital in Chicago, Illinois. Participants were 407 social worker-referred homeless adults with chronic medical illnesses (89% of referrals). Study intervention included 1) usual care which included standard discharge planning from hospital social workers, or 2) housing offered as transitional housing after hospitalization discharge, followed by placement in long-term housing and case management offered on-site at a) primary study sites, 2) transitional housing, and 3) stable housing sites. The main outcome measures included 1) hospitalizations, 2) hospital days, and 3) emergency department visits measured using electronic surveillance, medical records, and interviews. Models were adjusted for baseline differences in demographics, insurance status, prior hospitalization or emergency department visit, human immunodeficiency virus infection, current use of alcohol or other drugs, mental health symptoms, and other factors. The analytic sample (n = 405 [n = 201 for the intervention group, n = 204 for the usual care group]) was 78% men and 78% African American, with a median duration of homelessness of 30 months. After 18 months, 73% of participants had at least 1 hospitalization or emergency department visit. Compared with the usual care group, the intervention group had unadjusted annualized mean reductions of 0.5 hospitalizations, 2.7 fewer hospital days, and 1.2 fewer emergency department visits. Adjusting for baseline covariates, compared with the usual care group, the intervention group had a relative reduction of 29% in hospitalizations, 29% in hospital days, and 24% in emergency department visits. According to the authors, offering housing and case management to a population of homeless adults with chronic medical illnesses resulted in fewer hospital days and emergency department visits, compared with usual care.

Sedentary behavior and physical activity may be independent risk factors for psychological distress in adolescents, although there is no existing information for children. As a result, a study published in Pediatrics (2009;123:1263-1268) examined the cross-sectional association between psychological distress, television and screen entertainment time, and physical activity levels among a representative sample of children aged 4 to 12 years. Data were derived from the 2003 Scottish Health Survey and study participants included 1,486 boys and girls (mean age: 8.5 � 2.3 years). The parents completed the Strengths and Difficulties Questionnaire and information on television and screen entertainment time, physical activity, and dietary intake of their children. Results showed an abnormally high Strengths and Difficulties Questionnaire total difficulties score (20-40) in 4.2% of the sample. Approximately 25% of the children were exposed to television and screen entertainment at least 3 hours/day. In general linear models, television and screen entertainment time per week and physical activity levels were independently associated with the Strengths and Difficulties Questionnaire total difficulties score after adjustment for covariates. There was also an additive interaction effect showing that the combination of high television and screen entertainment time and low physical activity was associated with the highest Strengths and Difficulties Questionnaire score. Higher television and screen entertainment exposure (>2.7 hours/day) alone resulted in a 24% increase in the Strengths and Difficulties Questionnaire score in comparison with lower television and screen entertainment exposure (<1.6 hours/day). However, when combined with low physical activity this resulted in a 46% increase. According to the authors, higher levels of television and screen entertainment time and low physical activity levels interact to increase psychological distress in young children.

The FDA approved Creon (pancrelipase), a pancreatic enzyme replacement product designed to help patients with cystic fibrosis and others with exocrine pancreatic insufficiency (EPI) digest and absorb nutrients from foods. Creon is the first FDA-approved delayed-release pancreatic enzyme replacement product to be marketed in the US as a result of the agency’s unapproved drugs initiative. Creon, which contains a mixture of digestive enzymes extracted from the pancreas of pigs, helps patients lacking the enzymes needed to digest fats, proteins and sugars from food. Creon is approved for use in pediatric and adult patients. The FDA had required the manufacturer of Creon to submit, and the agency has approved, a Risk Evaluation and Mitigation Strategy (REMS), which includes a Medication Guide, to advise patients on risks associated with high doses of Creon, and the theroretical risk of transmission of viral disease from pigs to patients. A rare bowel disorder, called fibrosing colonopathy, can result from a patient’s high-dose use of Creon. While this condition is serious and may require surgery, a patients’ chances of having this condition may be reduced through their adherence to dosing instructions in the labeling. The risks of a rare bowel disorder and viral transmission described in the Medication Guide are considered to be risks related to all porcine (pig)-derived pancreatic enzyme products, including Creon. Instructions for dosing based on weight and age should be followed carefully. Creon may be sprinkled on food. Because Creon is a delayed-release drug, patients should never crush or chew the capsule as this would cause an early release of the enzymes and a reduction in enzyme activity. The FDA’s Office of Compliance and Office of New Drugs within CDER worked with Creon’s manufacturer, Solvay Pharmaceuticals, through the agency’s unapproved drugs initiative to help the company come into compliance with federal laws by obtaining FDA approval. The agency continues to encourage the manufacturers of all other unapproved pancreatic enzyme products (PEPs) to work with the agency to obtain market approval. All PEPs must obtain FDA approval by April 28, 2010, or be removed from the marketplace. People who are allergic to pork and pork products, suffer from gout or kidney disease, have difficulty swallowing, are pregnant or who plan to become pregnant, or are breastfeeding, should discuss the use of Creon with their health care professional.  Common side effects of Creon include flatulence (gassiness), abdominal pain, headache, and dizziness. Creon and other pancreatic enzyme products are made from pancreatic organs of pigs used for food. There is a theoretical risk of contracting a viral infection from pig-derived medicines, but no human illness has been reported. 

 

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