Tuberculosis (TB) continues to pose a major global health threat. Someone in
the world is newly infected with TB bacteria every second. Every year, more
than 9 million people develop active TB and it claims about 2 million lives.
In Canada, the overall incidence of TB has declined, but rates remain high
among immigrants from endemic countries and among Aboriginal populations.
Currently, Nunavut is facing the largest TB outbreak in the territory’s
10-year history.

In the days leading up to World TB Day 2011 on March 24, a team of
researchers from McGill University and the Research Institute of the McGill
University Health Centre (RI MUHC) is officially launching the BCG World
Atlas: a first-of-its-kind, easy-to-use, searchable website that provides
free detailed information on current and past TB vaccination policies and
practices for more than 180 countries.

“The Atlas is designed to be a useful resource for clinicians, policymakers
and researchers alike,” said co-author Dr. Madhukar Pai, who is an assistant
professor at McGill’s Dept. of Epidemiology, Biostatistics & Occupational
Health and a researcher in the Respiratory Epidemiology and Clinical
Research Unit at the Montreal Chest Institute and the RI MUHC. “It has
important implications on diagnosing and treating TB and on the research
that’s being done on developing a new TB vaccine.”

Pai is a senior author on a paper about the BCG World Atlas that will be
published in the March edition of the journal PLoS Medicine.

The Bacille Calmette-GuГ©rin (BCG) vaccine was introduced in 1921 and
continues to be the only vaccine used to prevent TB. Despite nearly a
century of use, the vaccine remains controversial, with known variations in
efficacy, strains, policies and practices across the world. Clinicians need
to be aware of the various BCG policies in different parts of the world, as
well as changes to those policies over time, especially when dealing with
foreign-born adults who were vaccinated as children and who are unlikely to
have retained their childhood vaccination records.

Ms. Alice Zwerling, BCG Atlas project leader and PhD candidate in
epidemiology at McGill, explained that BCG vaccination can cause false
positives in the skin test that’s routinely used to screen for latent TB.
“As a clinician, if you’re trying to interpret the skin test in a
foreign-born person, you’re going to want to know when the BCG vaccination
was given back home and how many times it has been given. The Atlas provides
this information and can help doctors decide on when to use the newly
available blood tests for TB that are not affected by BCG vaccination,” she
added.

“I am pleased that the Public Health Agency of Canada (PHAC) could play a
part in such an important project,” said Dr. David Butler-Jones, Canada’s
Chief Public Health Officer and the head of PHAC, which provided funding for
this project. “The BCG World Atlas will be a vital resource for
practitioners across Canada, one that will help us prevent and control the
spread of TB here at home.”

The Atlas project began in 2007 with the compilation of detailed information
on past and present BCG vaccination policies on as many countries as
possible. The data were assembled through respondent-completed
questionnaires, published papers, reports, government policy documents and
data available from the World Health Organization Vaccine Preventable
Diseases Monitoring System. The beta version of the site went live in 2008
and over the past year more than 6,000 visits have been recorded with a
steady increase in traffic over time. The Atlas is constantly being updated
and its authors welcome input from countries that are currently not covered.

BCG Atlas Video

BCG World Atlas

Link to Article

Source
McGill University

Medical scientists detected early atherosclerosis by uncovering vascular abnormalities in 42- to 44-year-old predominately male patients who had severe obstructive sleep apnea but no overt cardiovascular disease.

In the study, the researchers investigated the functional and structural properties of the large arteries in 15 persons with mild to moderate obstructive sleep apnea (OSA), 15 individuals with severe OSA, and 12 healthy control volunteers. All groups were matched for age, sex, and body mass index.

The participants underwent a full standard overnight sleep test (polysomnography); a pulse wave velocity test, which is a noninvasive, accurate method of determining the elastic properties of the aorta and other large arteries; and an assessment with a high definition echo-tracing device to measure carotid artery thickness, diameter, and potential enlargement.

The authors said that the mechanical properties of the large arteries are important determinants of circulatory physiology in health and disease. They noted that increased arterial stiffness preceded the onset of systemic hypertension in humans and was an independent risk marker of premature artery disease, atherosclerosis, and cardiovascular disease.

In OSA, the sleeping person repeatedly stops breathing as a result of partial or complete blockage of the upper airways. This stoppage occurs long enough to decrease the amount of oxygen in the blood and brain, and to build up carbon dioxide. After a breathing pause of 10 seconds or longer, the person usually awakens enough to resume breathing. These episodes can occur numerous times during the night.

In this study, the investigators said that an important finding was the increased carotid diameter in patients with OSA. It seems that previous studies have shown that carotid artery dilation is a compensatory mechanism in the early stages of atherosclerosis.

The authors pointed out that all vascular abnormalities detected correlated significantly with the severity of the subject’s OSA, which further supported the hypothesis that OSA plays an independent role in the progression of atherosclerosis.

The study appears in the first issue for September 2005 of the American Thoracic Society’s peer-reviewed American Journal of Respiratory and Critical Care Medicine.

Brian Kell
bkellthoracic
212-315-6442
American Thoracic Society
thoracic
American Thoracic Society Journal news tips for September 2005 (first issue)

For the complete text of these articles, please see the American Thoracic Society Online Web Site at http//www.atsjournals. For either contact information or to request a complimentary journalist subscription to ATS journals online, or if you would like to add your name to the Society’s twice monthly journal news e-mail list, contact Brian Kell at (212) 315-6442, or by e-mail at bkellthoracic.

Will Cross became the first American with diabetes to summit Mount Everest, the highest point on earth on which a human can walk without supplemental oxygen.1 With this achievement, Cross, a 39-year-old father of six from Pittsburgh sponsored by NovoLog® (insulin aspart [rDNA origin] injection), became the first in the world with diabetes to climb the highest mountain on each of the seven continents and trek to the North and South Poles, a multi-year odyssey known as the NovoLog® Peaks and Poles Challenge. He reached the summit at approximately 5:10 a.m. local time.

“Will Cross is making international history by completing the grueling four-year NovoLog Peaks and Poles Challenge – a remarkable human feat for anyone with or without diabetes,” said Andrew Purcell, Vice President of Strategic Business Development at Novo Nordisk, a world leader in diabetes care and developer of NovoLog. “Novo Nordisk and NovoLog are proud to have played such an important role in this lifetime achievement and to celebrate an important milestone in Novo Nordisk’s 83-year heritage of diabetes advances.”

During the expedition to the 29,035-foot summit of Mount Everest the former high school principal who is living with type 1 diabetes battled record-breaking winds, constant freezing temperatures, and dangerous ice including an April icefall avalanche. Compromised food and gear deliveries and limited communications due to political turmoil in the region also impacted his climb.

Cross uses NovoLog insulin, an analog insulin that mimics the body’s normal meal-time insulin response. He relies on NovoLog® FlexPen®, a pre-filled disposable delivery device designed to simplify injections, giving Cross flexibility in administering his insulin.

“Experiencing a peak or low blood sugar level can be life-threatening for anyone living with diabetes, especially someone crossing a 40-feet deep crevasse,” said Cross. “The freedom to eat when I needed to and to inject insulin within ten minutes of my meals with NovoLog FlexPen allowed me the flexibility that played a vital role in making it to the highest peak in the world.”

Cross, who is the subject of a recently released documentary, “Peaks and Poles: The Will Cross Story,” succeeded on his third attempt at the summit, after he was forced to turn back twice (in 2004 and 2005) due to weather and a shortage of oxygen. He will continue to inspire people affected by diabetes at speaking events across the country throughout the remainder of the year. For more information visit peaksandpoles.

About the NovoLog Peaks and Poles Challenge

The NovoLog Peaks and Poles Challenge is the pinnacle of exploration achievement that involves walking to the North and South Poles and climbing to the summit of the highest mountain on each of the seven continents. Will Cross is the first in the world with diabetes to complete it. Challenge stops include:

– North & South Poles

– Denali, Alaska

– Mount Vinson, Antarctica

– Mount Everest, Nepal

– Mount Kilimanjaro, Tanzania

– Mount Aconcagua, Argentina

– Mount Kosciusko, Australia

– Mount Elbrus, Russia

Further information can be found at peaksandpoles.

About Diabetes

Diabetes, a disease in which the body does not produce or properly use insulin, affects 20.8 million people in the US or seven percent of the population. Of those living with the disease 6.2 million people (or nearly one-third) are unaware that they have the condition, and of those who have been diagnosed 10 million are in poor control. Diabetes is the sixth leading cause of death by disease in the US and costs an estimated $132 billion per year in medical expenses and lost productivity. According to the World Health Organization, the total number of people with diabetes worldwide is projected to rise from 171 million in 2000 to 366 million in 2030.

Type 1 diabetes results from the body’s failure to produce insulin, the hormone that “unlocks” the cells of the body, allowing glucose to enter and fuel them. It is estimated that 5-10 percent of Americans who are diagnosed with diabetes have type 1 diabetes. Type 2 diabetes results from insulin resistance (a condition in which the body fails to properly use insulin), combined with relative insulin deficiency. Most Americans who are diagnosed with diabetes have type 2 diabetes. Research studies in the United States and abroad have found that improved glycemic control benefits people with either type 1 or type 2 diabetes.

About NovoLog

NovoLog is a rapid acting form of insulin for the treatment of patients with diabetes mellitus (type 1 and type 2) for the control of hyperglycemia. It enters the bloodstream quickly and begins working within minutes to lower blood glucose. The rapid onset and short duration of action mimic the insulin action of a person without diabetes. NovoLog offers convenient mealtime dosing and should be dosed immediately or up to 10 minutes before a meal. NovoLog is available in the prefilled NovoLog FlexPen insulin delivery system and is approved for use in insulin pumps.

NovoLog is contraindicated during episodes of hypoglycemia and in patients hypersensitive to insulin aspart or one of its excipients. Hypoglycemia is the most common adverse effect of insulin therapy, including NovoLog. See package insert for more details. NovoLog was originally approved by the FDA for use in adults in the U.S. in 2000.

Because it has a more rapid onset and shorter duration of action than regular human insulin, NovoLog should normally be used in regimens together with an intermediate or long-acting insulin, and injection of NovoLog should immediately followed by a meal.

Any change in insulin should be made cautiously and only under medical supervision.

Novo Nordisk is a healthcare company with an 80-year history of innovation and achievement in diabetes care. In addition to diabetes care, Novo Nordisk has a leading position within areas such as hemostasis management, growth hormone therapy, and hormone therapy for women. Novo Nordisk’s business is driven by the Triple Bottom Line: a commitment to economic success, environmental soundness, and social responsibility to employees and customers. With headquarters in Denmark, Novo Nordisk employs approximately 22,000 full-time employees in 79 countries, and markets its products in 179 countries. Novo Nordisk’s B shares are listed on the stock exchanges in Copenhagen and London. Its ADRs are listed on the New York Stock Exchange under the symbol ‘NVO’. For global information, visit novonordisk; for United States information, visit novonordisk-us.

1PBS. Lost of Everest. Accessed April 26, 2006.

View drug information on Novolog Mix 70/30.

Researchers have identified a stage during dopamine neuron differentiation that may be an ideal time to collect human embryonic stem cells for transplantation to treat Parkinson’s disease, according to data presented at Neuroscience 2008, the 38th annual meeting of the Society for Neuroscience.

Lorraine Iacovitti, Ph.D., professor and interim director of the Farber Institute for Neurosciences of Thomas Jefferson University, and her research team found that neural progenitor cells that express the gene Lmx1a are committed to the midbrain dopamine neuron lineage, but still retain proliferative capacity. Because of these characteristics, the stage at which Lmx1a is expressed may be ideal for transplantation.

“Identifying the subset of developing dopamine neurons and selecting those cells at the stage appropriate for their transplantation has been challenging,” said Dr. Iacovitti. “Our research demonstrates that we are now able to grow neurons and select the ones that may work as a therapy, without the use of synthetic genes. This advance represents an important leap forward in the quest to devise a viable cell replacement therapy for Parkinson’s disease.”

The Lmx1a-positive cells cannot be identified solely by this transcription factor. However, Dr. Iacovitti and her team also found that a large percentage of the Lmx1a-positive cells express a cell surface protein called TrkB. This protein was not expressed on any of the other cell types identified in the cell culture. With TrkB as a cell surface marker, dopamine neuron progenitor cells derived from human embryonic stem cells can be selected from a heterogenous population using magnetic-activated cell sorting (MACS) or fluorescence-activated cell sorting (FACS). Neither process alters the stem cell’s genome. Dr. Iacovitti and her team are now testing the ability of these cells to counteract Parkinson’s disease in animal models. They will also be adapting these procedures developed in human embryonic stem cells to adult-derived human induced-pluripotent stem cells.

###

According to the National Parkinson Foundation, Parkinson’s disease affects one in 100 people over the age of 60. The disease is caused by the loss of dopamine neurons, which help control movement, cognition and other critical brain functions. Although there are treatments for the symptoms of Parkinson’s disease, none of the treatments appear to slow or stop the progression of the disease. Human embryonic stem cell transplantation represents a promising method for replacement of the lost dopamine neurons, since mature dopamine cells do not survive harvest and transplantation.

Source: Emily Shafer

Thomas Jefferson University

A newly released independent analysis of the Medicare-approved drug discount cards has found that average seniors participating in the new program will save over $1,200, on average, for their prescription drug purchases ЁC before the full Medicare drug benefit goes into effect in 2006.

The new study examined 150 prescription drugs used most often by those on Medicare, and found that many of the cards saving nearly 20 percent off the retail price of drugs. The report was conducted by the The Lewin Group, a nonpartisan nationally recognized economic analysis company.

This new report comes on the heels of other recent reviews — by the Kaiser Family Foundation, the American Enterprise Institute and Medicare — which have also documented the cost savings seniors are achieving.

“Despite some of the unfortunate misinformation going around, this new report, and others like it, show that seniors who don’t sign up for the Medicare approved drug discount cards are leaving money on the table. I again encourage seniors who need help to check out what is available,” said Sen. Larry Craig, Chairman of the U.S. Senate Special Committee on Aging.

The savings vary depending on the state you live in and which card you sign up for. In Craig’s home state of Idaho, for example, a typical senior will spend $3,444 on prescription medications during the eighteen month period before the full Medicare program goes into effect in January of 2006. During that time, the new study found that an Idaho senior with a Medicare-approved discount drug card could save $1,057.

Researchers said that low-income seniors would save the most money because they would receive $600 federal low-income credit to help them purchase their medications and be eligible for additional drug company help if and when their $600 in assistance has been spent. Under the new benefit program, low-income seniors who qualify will receive $600 in 2004 and another $600 in 2005 to help buy medications.

“Those that need help with their prescriptions should call 1-800-MEDICARE to find out how they can get the discount card that will best meet their needs. Telephone lines are open 24 hours a day, seven days a week. Over 3000 people are now available to answer your call, and waiting times are down to two minutes,” Craig said.

Before you call 1-800-MEDICARE (1-800- 633-4227), Sen. Craig advises that you:

* Have with you a list of the names of the drugs you take, the size, and how often you take them.

* Know your total monthly income — you may qualify for the $600 per year in low income assistance. Your recent income statements or tax forms may be helpful in figuring out your monthly income.

The temporary Medicare-approved drug discount program will be replaced in 2006 when the full benefit goes into effect. Starting in 2006, about one in four seniors on Medicare will have a federal subsidy of 96-98 percent to cover their drug costs. Two out of every three seniors already have drug coverage from other sources which they can keep when the new program goes into effect.

Sign up to receive your own news THE CHAIRMAN OF THE U.S. SENATE SPECIAL COMMITTEE ON AGING.

From the US Senate Special Committee on Aging

Oxygen levels in the lab can permanently alter human embryonic stem (ES) cells, specifically inducing X chromosome inactivation in female cells, according to Whitehead Institute researchers. Human ES cells have been routinely created and maintained at atmospheric levels of oxygen, which is about 20%. Cells in the body are usually exposed to only 1-9% oxygen.

“When human ES cells are isolated at 20% oxygen, they are stressed and they inactivate one X chromosome in female cells,” says Founding Whitehead Member Rudolf Jaenisch. “This argues that the conventional way to make human ES cells is not optimal. We’re not saying our method is the only way or the best possible way, but it is better than the conventional method.”

These results are published in the online issue of Cell.

Scientists are interested in human ES cells because they have the ability to mature into almost any cell type in the body, a trait known as pluripotency. Theoretically, this potential could be used to treat diseases or injuries.

“Also, human ES cells are the only tool we have to study the beginning of human development,” says Maisam Mitalipova, Director of the Whitehead Human Stem Cell Facility and designer of the study reported in Cell.

But human ES cells, even from the same cell lines, have been yielding different results in experiments. Inconsistent results may call into question an experiment’s methods or conclusions.

“The huge variation from lab to lab in culturing and isolating ES cells is one of the big problems in the field,” says Christopher Lengner, first author of the Cell paper and a postdoctoral researcher in the Jaenisch lab. “Just because of their growing conditions, the cells can be completely different from each other. So, we wanted to get back to the basics and really establish a ground state for how we isolate these cells and how we maintain them in the most pristine way possible.”

Human ES cells are usually derived from fertilized eggs that were designated for research by patients of in vitro fertilization (IVF) clinics. After an embryo grows to a ball of about 100 cells, researchers remove the ES cells. Traditionally, all of this work, from creating the fertilized eggs at the IVF clinic to the isolation and maintenance of the human ES cells in the lab, has been performed at atmospheric levels of oxygen. The resulting human ES cells display multiple differences in their genomes indicating they are at a slightly less flexible and pluripotent state than are mouse ES cells.

For example, after early random inactivation, female human ES cells always have the same X chromosome inactivated while mouse ES cells have two active X chromosomes until the cells begin differentiating, when one of the X chromosomes is randomly inactivated in each cell. X inactivation is vital for proper development in a female cell. If both X chromosomes are left active in an adult cell, the cell will have twice the expression of the X chromosome genes, which is fatal.

To test how oxygen levels during isolation and culture affect human ES cells, Mitalipova created six new human ES cell lines – two male and four female. Half of the cells isolated from each embryo were cultured in 20% oxygen, while the other half were created and maintained at 5% oxygen. The researchers then looked not only at the all of the genes expressed in these cells but also at their epigenetic state.

“When you expose the human ES cells to atmospheric oxygen for just a few days, the whole genome goes crazy – there are massive gene expression changes,” says Lengner.

But after a period of time the human ES cells adapt to the atmospheric oxygen and almost all of these changes normalized again, except for the X inactivation gene XIST, which remained strongly switched on. When Alexander Gimelbrant, who is Assistant Professor at Dana Farber Cancer Institute and co-first author of the article, checked, the female human ES cells exposed to 20% oxygen had one X chromosome permanently inactivated. However, the human ES cells derived at 5% oxygen did not exhibit the strong activation of the XIST gene, and both X chromosomes in the female cells remained active – an indication that these cells were in a more developmentally pristine state than their counterparts cultured in atmospheric oxygen.

Although this work focused on the effects of environmental oxygen levels, other factors may have similar negative effects on human ES cells.

“It seems that stress in general, like inefficiently freezing cells in the laboratory or embryos at the IVF clinic or manipulating the cells a lot, can make the cells inactivate an X chromosome and lose some pluripotency,” says Mitalipova.

Even if these stressors, including a high oxygen level, are eliminated, the human ES cells still are not as pluripotent as mouse ES cells.

However, in a paper published earlier this month in the Proceedings of the National Academy of Sciences (PNAS), Jacob Hanna in the Jaenisch lab describes two approaches to push existing and newly established human ES cells to the more pluripotent state seen in mouse ES cells. Hanna’s methods rely either on genes inserted into the ES cells’ DNA or on drugs added to the culture medium surrounding the cells, which appears to keep human ES cells in the more pluripotent state.

Notes:

This research was supported by Hillel and Liliana Bachrach and Susan Whitehead.

Rudolf Jaenisch’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology at Massachusetts Institute of Technology.

Full Citations:

“Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations”

Cell, online May 13, 2010.

Christopher J. Lengner (1,11), Alexander A. Gimelbrant (4,5,11), Jennifer A. Erwin (6,7,8), Albert Wu Cheng (1,3), Matthew G. Guenther (1), G. Grant Welstead (1), Raaji Alagappan (1), Garrett M. Frampton (1,2), Ping Xu (1), Julien Muffat (1), Sandro Santagata (1), Doug Powers (9), C. Brent Barrett (10), Richard A. Young (1,2), Jeannie T. Lee (6,7,8), Rudolf Jaenisch (1,2) and Maisam Mitalipova (1).
Whitehead Institute for Biomedical Sciences, 9 Cambridge Center, Cambridge, MA 02142, USA
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Department of Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
Department of Pathology, Harvard Medical School, Boston, MA 02114, USA
Department of Genetics, Harvard Medical School, Boston, MA 02114, USA
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
Howard Hughes Medical Institute
Incept Biosystems, Ann Arbor, MI 48108, USA
Boston IVF, The Waltham Center, Waltham, MA 02451, USA
These authors contributed equally to this work

“Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs”


PNAS, May 3, 2010.

Jacob Hanna (1), Albert W. Cheng (1,2), Krishanu Saha (1), Jongpil Kim (1), Frank Soldner (1), John P. Cassady (1,3), Christopher J. Lengner (1), Bryce W. Carey (1,3), and Rudolf Jaenisch (1,3).
The Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
Computational & Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02142.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.

Source:
Nicole Giese
Whitehead Institute for Biomedical Research

Sangart, Inc., has announced positive results from its Phase IIa proof-of-concept study of MP4OX (oxygenated pegylated hemoglobin) in severely injured trauma patients with hemorrhagic shock causing lactic acidosis. The study demonstrated that MP4OX, when given in addition to standard of care, was effective at decreasing lactate levels in treated patients. During hemorrhagic shock, inadequate perfusion of critical organs can lead to insufficient oxygenation of tissues, which can be detected by an increase in lactate levels. MP4OX is a novel oxygen therapeutic agent that is designed to provide rapid oxygen delivery to ischemic tissues.

Study data show a statistically significant greater immediate and sustained decrease of lactic acid in patients treated with MP4OX compared to patients in the control group. The study also found that a greater proportion of patients treated with MP4OX were able to attain normal lactate levels as early as four hours post-treatment. Furthermore, data demonstrated a strong trend toward outcomes benefits through multiple measures, including reducing the average total number of days patients spent in hospital. In patients treated with MP4OX, the median hospital stay was half that of the control group. Serious adverse events were of equal rates and similar in nature between the MP4OX-treated and control groups.

“Trauma patients suffer organ dysfunction from shock and lack of oxygen supply to vital tissues. Prolonged lactic acidosis, a marker of shock, correlates with a worse outcome and higher mortality rate. This study suggests that MP4OX has the ability to improve oxygen delivery to the body and subsequently reduce organ failure and other complications.” said Karim Brohi, Professor of Trauma Sciences at Barts and the London School of Medicine & Dentistry and lead study investigator. “We are excited by the results from this study as they suggest that MP4OX has the potential to improve patient outcomes compared to the current standard of care in trauma.”

The clinical trial was a multi-center, randomized, double-blind, controlled study that enrolled 51 patients who suffered trauma-induced severe hemorrhagic shock across 11 clinical sites in the United Kingdom, Germany, France and South Africa. The primary objective of the study was to measure reduction in lactate levels after infusion of MP4OX.

“The positive safety and efficacy data from this trial suggest that MP4OX could be a promising new treatment option for patients suffering an acute traumatic injury,” said Brian O’Callaghan, President and Chief Executive Officer of Sangart. “Based on these results, we plan to further development and clinical evaluation of MP4OX and initiate Phase IIb clinical studies in trauma patients. This study further reinforces the promise of our MP4 platform in the development of medicines designed to enhance the delivery of oxygen to tissues and organs that are oxygen deprived.”

About Trauma

Traumatic injuries, including both penetrating trauma injuries such as bullet and knife wounds and blunt trauma from car accidents and falls, cause the death of over 5 million people each year world-wide. Trauma is the leading cause of death in people under the age of 44. Despite optimal care, many patients treated for traumatic injuries suffer organ dysfunction and failure. Elevated lactate levels (lactic acidosis), which indicate hypoperfusion and anaerobic metabolism (oxygen deprivation) in tissues and organs in the body, represent metabolic failure and also cardiovascular, renal and hepatic dysfunction. Prolonged lactic acidosis correlates with worse outcomes and higher mortality.

About MP4

Sangart’s product platform is based on the MP4 molecule, an investigational biopharmaceutical product designed to enhance the perfusion of oxygen-deprived (ischemic) tissues and provide targeted oxygen delivery in the capillaries. Using a novel pegylation approach, Sangart produces the MP4 molecule designed at the optimal oxygen affinity, diffusion potential and molecular size to perfuse capillaries and target oxygen delivery to tissues specifically at risk of ischemia.

Source:
Lauren Hamilton
Edelman Public Relations

Sanofi Pasteur, the vaccines division of sanofi-aventis Group
(EURONEXT : SAN and NYSE : SNY), announced today that its investigational
tetravalent dengue vaccine is entering into a pediatric clinical study in
Thailand to assess the efficacy of the vaccine in protecting children against
dengue, the most widespread tropical disease after malaria. Sanofi Pasteur’s
tetravalent dengue vaccine candidate is the first to reach this stage of
clinical development.

Sanofi Pasteur is collaborating with Mahidol University of
Thailand, the Ministry of Public Health, and the Pediatric Dengue Vaccine
Initiative (PDVI) to conduct this efficacy study in the province of
Ratchaburi.

“Large scale pediatric studies are instrumental for the
development of a safe and efficacious dengue vaccine to protect against a
disease that primarily affects children,” said Dr. Pratap Singhasivanon, Dean
of the Faculty of Tropical Medicine, Mahidol University. “We are happy to
contribute to an important milestone with the actual start of an efficacy
study in Ratchaburi.”

The Sanofi Pasteur clinical study program follows guidelines
from the Initiative for Vaccine Research (IVR) led by the World Health
Organization (WHO), which fosters the global efforts towards dengue vaccine
development.

“WHO is committed to the availability of a dengue vaccine that
will ultimately benefit children in endemic countries,” said Dr. Joachim
Hombach, Coordinator Implementation Research for IVR, WHO.

About Sanofi Pasteur dengue vaccine global clinical study
program

Sanofi Pasteur started the development of a dengue vaccine in
the 90′s. Clinical studies with the most advanced tetravalent candidate
vaccine started in the 2000′s. In a study in the United States, immunization
with three doses of Sanofi Pasteur’s tetravalent dengue vaccine candidate
generated a sero-neutralizing antibody response against all four serotypes of
the virus responsible for dengue fever in 100 percent of adults who
participated in the trial(1). The Sanofi Pasteur dengue vaccine research
program includes ongoing clinical studies in Mexico, Peru, and The
Philippines with adults and children.

About dengue fever

Dengue fever is a mosquito-borne disease caused by four types
of dengue viruses (type 1 to 4). Overall, the disease is a potential threat
for almost half the world’s population. Of the estimated 230 million people
infected annually, two million, mostly children, develop dengue hemorrhagic
fever (DHF), a severe form of the disease(2). DHF is a leading cause of
hospitalization in South-East Asia, placing tremendous pressure on strained
medical resources.

Dengue fever occurs mostly in tropical and subtropical
countries and is spreading to new parts of the globe each year. The WHO has
warned that the Western Pacific Region may be heading for a major dengue
outbreak(3). Outbreaks recently have been observed in Paraguay and the Middle
East. In addition, dengue affects countries such as Australia (Queensland)
and the United States (Puerto Rico, Texas-Mexico border, Hawaii and the
US-affiliated Pacific Islands). A substantial number of people traveling to
endemic regions are also infected each year.

About sanofi-aventis

Sanofi-aventis, a leading global pharmaceutical company,
discovers, develops and distributes therapeutic solutions to improve the
lives of everyone. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in
New York (NYSE: SNY).

Sanofi Pasteur, the vaccines division of sanofi-aventis Group, provided
more than 1.6 billion doses of vaccine in 2008, making it possible to
immunize more than 500 million people across the globe. A world leader in the
vaccine industry, Sanofi Pasteur offers the broadest range of vaccines
protecting against 20 infectious diseases. The company’s heritage, to create
vaccines that protect life, dates back more than a century. Sanofi Pasteur is
the largest company entirely dedicated to vaccines. Every day, the company
invests more than EUR 1 million in research and development. For more
information, please visit: sanofipasteur

References:

1. Data generated by the WHO Flavivirus Laboratory Reference Center,
Mahidol University, Bangkok, Thailand, presented at the American Society of
Tropical Medicine and Hygiene’s (ASTMH) 56th annual meeting held in
Philadelphia, Pennsylvania, USA

2. Pediatric Dengue Vaccine Initiative (PDVI), presentation “Estimating
the global burden of dengue” at 2nd Int Conf on Dengue & DHF, 15-17 Oct 08 ,
Phuket, Thailand

3. WHO alarmed about the spread of dengue,
wpro.who.int/media_centre/press_releases/pr_23072007.htm

Forward Looking Statements

This press release contains forward-looking statements as
defined in the Private Securities Litigation Reform Act of 1995, as amended.
Forward-looking statements are statements that are not historical facts.
These statements include product development, product potential projections
and estimates and their underlying assumptions, statements regarding plans,
objectives, intentions and expectations with respect to future events,
operations, products and services, and statements regarding future
performance. Forward-looking statements are generally identified by the words
“expects,” “anticipates,” “believes,” “intends,” “estimates,” “plans” and
similar expressions. Although sanofi-aventis’ management believes that the
expectations reflected in such forward-looking statements are reasonable,
investors are cautioned that forward-looking information and statements are
subject to various risks and uncertainties, many of which are difficult to
predict and generally beyond the control of sanofi-aventis, that could cause
actual results and developments to differ materially from those expressed in,
or implied or projected by, the forward-looking information and statements.
These risks and uncertainties include among other things, the uncertainties
inherent in research and development, future clinical data and analysis,
including post marketing, decisions by regulatory authorities, such as the
FDA or the EMEA, regarding whether and when to approve any drug, device or
biological application that may be filed for any such product candidates as
well as their decisions regarding labelling and other matters that could
affect the availability or commercial potential of such products candidates,
the absence of guarantee that the products candidates if approved will be
commercially successful, the future approval and commercial success of
therapeutic alternatives as well as those discussed or identified in the
public filings with the SEC and the AMF made by sanofi-aventis, including
those listed under “Risk Factors” and “Cautionary Statement Regarding
Forward-Looking Statements” in sanofi-aventis’ annual report on Form 20-F for
the year ended December 31, 2007. Other than as required by applicable law,
sanofi-aventis does not undertake any obligation to update or revise any
forward-looking information or statements.

Sanofi Pasteur

A new study analyzing the prevalence of sensory impairment among older U.S. workers found that hearing impairment prevalence was three times that of visual impairment, and that 38 percent of older workers reported experiencing either impairment.

Using 1997-2004 national survey data, researchers evaluated the prevalence of sensory impairment among U.S. workers age 65 years and older. Farm operators, mechanics and motor vehicle operators had the highest prevalence of sensory impairment.

The study’s authors conclude, “Our findings suggest a need for preventative measures among potentially vulnerable worker groups with sensory impairment. Research is needed to determine whether sensory aids and other workplace accommodations enhance worker productivity and job satisfaction as well as reduce injury risk.”

Source
American Journal of Public Health

A common smoking cessation therapy used to help reduce adverse events associated with nicotine withdrawal may actually increase the risk of death for smokers admitted to the intensive care unit (ICU). In a new study presented at CHEST 2006, the 72nd annual international scientific assembly of the American College of Chest Physicians (ACCP), researchers found that smokers admitted to the ICU who received nicotine replacement therapy (NRT) during their stay had a higher risk of death than smokers who did not receive NRT.

“In some critically ill patients, the development of nicotine withdrawal symptoms can worsen their prognosis. As a result, NRT is given to active smokers in the ICU to prevent nicotine withdrawal symptoms,” said lead researcher Amy Lee, MD, Mayo Clinic College of Medicine, Minneapolis, MN. “The hemodynamic effects of nicotine may lead to increased heart rate, systemic arterial blood pressure, and constriction of the coronary arteries. Although these potential adverse effects of NRT have not been shown to worsen the prognosis of healthy volunteers and patients with stable coronary artery disease, they may be detrimental in critically ill patients.”

Lee and colleagues examined the safety of NRT in the ICU by reviewing the medical records of 112 smoking patients admitted to the ICU who received NRT during their stay. Researchers compared patient outcomes between the NRT group and a control group. Among the patients who received NRT, 18 deaths (16.1%) occurred, compared with the 3 deaths (2.7%) in the control group. The hospital mortality rate was 21.4% for the NRT group, compared with 5.4% in the control group. Furthermore, when researchers controlled for severity of illness, NRT was found to be an independent risk factor for mortality (odds ratio 17.0).

There were no statistically significant differences in age, gender, ethnicity, and severity of illness measured by APACHE III prognostic model between the NRT and control groups. The median ICU length of stay for the NRT group was 24.4 (16.1 – 63.6) hours, compared with 22.6 (14.0 – 42.8) hours for the control group. The median hospital length of stay was 29.6 (18.3 – 127.1) hours, compared with 46.2 (19.8 – 117.3) hours for the control group.

“Although administering nicotine replacement therapy to smokers in the ICU is not a standard practice, some ICUs have nurse-driven protocols aimed at providing NRT for active smokers. We expect NRT to be more widely used in such ICUs,” said senior author Bekele Afessa, MD, FCCP, Mayo Clinic College of Medicine. Common signs of nicotine withdrawal include craving, irritability, depression, restlessness, and sleep disturbances. However, researchers caution that, because of other conditions that mimic nicotine withdrawal in the critically ill, to may be difficult to make an accurate diagnosis.

“Minimizing the effects of nicotine withdrawal in critically ill patients who smoke can present a significant challenge to the ICU team,” said Mark J. Rosen, MD, FCCP, President of the American College of Chest Physicians. “The findings of this study are intriguing and reinforce the need for additional research regarding the effects of nicotine replacement therapy on patients in the ICU.”

CHEST 2006 is the 72nd annual international scientific assembly of the American College of Chest Physicians, held October 21-26 in Salt Lake City, UT. ACCP represents 16,500 members who provide clinical respiratory, critical care, sleep, and cardiothoracic patient care in the United States and throughout the world. The ACCP’s mission is to promote the prevention and treatment of diseases of the chest through leadership, education, research, and communication.

Chest
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