Awakening Brain Stem Cells

MA-Scientists at Schepens Eye Research Institute have identified specific molecules in the brain that are responsible for awakening and putting to sleep brain stem cells, which, when activated, can transform into neurons (nerve cells) and repair damaged brain tissue. Their findings are published online this week in the Proceedings of the National Academy of Science (PNAS).

An earlier paper (published in the May issue of Stem Cells) by the same scientists laid the foundation for the PNAS study findings by demonstrating that neural stem cells exist in every part of the brain, but are mostly kept silent by chemical signals from support cells known as astrocytes.

“The findings from both papers should have a far-reaching impact,” says principal investigator, Dr. Dong Feng Chen, who is an associate scientist at Schepens Eye Research Institute and an assistant professor of ophthalmology at Harvard Medical School. Chen believes that tapping the brain??s dormant, but intrinsic, ability to regenerate itself is the best hope for people suffering from brain-ravaging diseases such as Parkinson’s or Alzheimer’s disease or traumatic brain or spinal cord injuries.

Until these studies, which were conducted in the adult brains of mice, scientists assumed that only two parts of the brain contained neural stem cells and could turn them on to regenerate brain tissue — the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). The hippocampus is responsible for learning and memory, while the SVZ is a brain structure situated throughout the walls of lateral ventricles (part of the ventricular system in the brain) and is responsible for generating neurons reponsible for smell. So scientists believed that when neurons died in other areas of the brain, they were lost forever along with their functions.

In the first study, Chen’s team learned that stem cells existed everywhere in the brain by testing tissue from different parts of adult mice brains in cultures containing support cells (known as astrocytes) from the hippocampus, where stem cells do regenerate.

In the cultures the stem cells from other brain regions came to life and turned into neurons.

When they compared the chemical makeup of the areas known to generate new neurons in the hippocampus with other parts of the brain, the team discovered that astrocytes in the hippocampus were sending one signal to the stem cells and that those from the rest of the brain were sending a different signal to stem cells.

In the second (PNAS) study, the team went on to discover the exact nature of those different chemical signals. They learned that in the areas where stem cells were sleeping, astrocytes were producing high levels of two related molecules — ephrin-A2 and ephrin-A3. They also found that removing these molecules (with a genetic tool) activated the sleeping stem cells.

The team also found that astrocytes in the hippocampus produce not only much lower levels of ephrin-A2 and ephrin-A3, but also release a protein named sonic hedghoc that, when added in culture or injected into the brain, stimulates neural stem cells to divide and become new neurons.

“These findings identify a key pathway that controls neural stem cell growth in the adult brain and suggest that it may be possible to reactivate the dormant regenerative potential by adding sonic hedgehoc, or blocking ephrin-A2 or ephrin-A3,” says Dr. Jianwei Jiao, the first author of the two papers.

The next step for the team will be to stimulate the sleeping stem cells in animals who are models of neurodegenerative disorders, such as Parkinson’s disease, to see if the brains can repair themselves and restore their damaged functions.

Schepens Eye Research Institute is an affiliate of Harvard Medical School and the largest independent eye research institute in the country.

Source: Patti Jacobs

Schepens Eye Research Institute

CIMZIA(R) (Certolizumab Pegol) Provides Rapid And Sustained Relief From Signs And Symptoms Of Rheumatoid Arthritis For Two Years

UCB announced results from several Phase III clinical trials evaluating CIMZIA(R) (certolizumab pegol) – the only PEGylated anti-TNF (Tumor Necrosis Factor)
- presented at the American College of Rheumatology (ACR) Annual Scientific
Meeting. Results from the open-label extension study to RAPID 1 met both
co-primary endpoints (American College of Rheumatology (ACR) 20 response(a)
scores at Week 24 and change from baseline in modified Total Sharp Scores
at Week 52). Results also showed that CIMZIA together with methotrexate
(MTX) provided ACR 20 response as early as Week 1 with sustained long-term
benefit in relieving symptoms of rheumatoid arthritis (RA) through 100
weeks.

Another analysis investigating the rapidity of response to CIMZIA as a
monotherapy (FAST 4WARD) and together with MTX (RAPID 1) was presented at
the meeting. Both studies met their primary endpoints (ACR20 response rate
at Week 24) with clinical and statistical significance. The analysis
presented showed that the response to CIMZIA treatment was rapid in both
studies with more than a third (36.7 percent) of patients receiving CIMZIA
as a monotherapy (FAST 4WARD) and nearly a quarter (22.9 percent) of
patients receiving CIMZIA together with MTX (RAPID 1) achieving an ACR20
response within one week, both significantly different from placebo. ACR20
response rates peaked at Week 12 in both studies and were sustained until
the end of the studies (Week 24 in FAST 4WARD; Week 52 in RAPID 1).

“The data show that treatment with CIMZIA in clinical trials produced a
fast and clinically meaningful effect for RA patients over an extended
period of time,” said Michael Schiff, M.D., study investigator and Clinical
Professor of Medicine at the University of Colorado School of Medicine.

CIMZIA had a low occurrence of treatment discontinuation due to adverse
events. The most commonly occurring adverse events were headache,
nasopharyngitis, and upper respiratory tract infections. Pooled safety data
from the two main phase III trials showed there was a low incidence of
injection site burning and stinging (n=

Additional data presented focused on the effect of treatment with
CIMZIA together with MTX in quality of life measurements. In RAPID 1,
nearly three-quarters of patients achieved improvements in physical
function when treated with CIMZIA together with MTX, including 72.4 percent
of those initially treated with CIMZIA 200 mg together with MTX or 70.1
percent of those treated with CIMZIA 400 mg together with MTX.

On a 10-point improvement on the Patients Assessment of Arthritis Pain
(PAAP) scale, the data showed an average improvement of 39.1 and 38.1
points for those on CIMZIA 200 mg together with MTX and CIMZIA 400 mg
together with MTX, respectively.

“It is exciting to see that these patients are deriving and maintaining
improvements on multiple levels with continued CIMZIA treatment,” noted
Philip Mease, M.D., study investigator at the Seattle Rheumatology
Associates and Director of Rheumatology Research at Swedish Medical Center.
“Reducing pain and discomfort from RA is extremely important, but it is
also noteworthy when patients find treatments that lead to a better overall
quality of life.”

In RAPID 1, patients treated with CIMZIA together with MTX reported
gains in additional work and household work days per month and productive
work and household work days per month as early as week 4. Over 6 months,
improvements continued compared to the control group. These improvements
were maintained for up to one year.

Additionally, data presented shows Health Reported Quality of Life
Measurements (HRQoL) approached population norms in the “vitality” and
“mental health” domains. As assessed by the Fatigue Assessment Scale of 1
to 10, patients in the trial also reported a mean reduction in fatigue to
3.1 points at week 100 with CIMZIA together with MTX treatment.

RAPID Clinical Trials Program

The international, multi-center, double-blind placebo-controlled RAPID
(RA PreventIon of structural Damage) clinical trials were designed to
establish the efficacy and tolerability of CIMZIA(R) (certolizumab pegol)
together with methotrexate (MTX) in the treatment of active rheumatoid
arthritis who did not adequately respond to conventional treatment. The
program is comprised of two large, international, multi-center
placebo-controlled studies – RAPID 1 (027) and RAPID 2 (050).

In the year-long RAPID 1 trial, patients randomly received one of three
treatment regimens: 393 patients received CIMZIA 400 mg at weeks 0, 2 and
4, then CIMZIA 200 mg together with MTX every two weeks; 390 patients
received CIMZIA 400 mg together with MTX every 2 weeks; 199 patients
received placebo together with MTX every 2 weeks. RAPID 1 met co-primary
endpoints: ACR20 response rate(a) at week 24 and the change from baseline
in mTSS(b) at week 52. An open-label extension study continued to evaluate
the effects of CIMZIA over two years.

In the six-month RAPID 2 trial, 619 patients randomly received one of
three treatment regimens: 246 patients received CIMZIA 400 mg at weeks O, 2
and 4, then CIMZIA 200 mg together with MTX every two weeks; 246 patients
received CIMZIA 400 mg together with MTX every two weeks; 127 patients
received placebo together with MTX every two weeks.

In all arms of the study, the dose of methotrexate was 10mg per week or
greater. Patients were assessed for improvement in signs and symptoms of
RA. The primary endpoint for the study RAPID 2 was ACR20 responder rate at
week 24.

In both studies, CIMZIA given at a dosage of 200mg every two weeks
produced similar clinical results as a dosage of 400mg every two weeks.

(a) ACR (American College of Rheumatology) response scores measure
improvement in the tender and swollen joint count and also include
assessment of the following five parameters: patient’s global assessment,
physician’s global assessment, patient’s assessment of pain, degree of
disability, and level of acute-phase reactant. ACR20 is achieved when there
is 20% improvement in the tender and swollen joint count as well as a 20%
improvement in at least three of the five parameters. ACR50 & ACR70 are an
extension of these criteria corresponding to a 50% and 70% improvement
respectively. (1)

(b) Modified Total Sharp Scores (mTSS) is a measurement used to assess
changes in bone erosion and joint-space narrowing measured by X-ray. A
smaller change in mTSS reflects less progression of joint damage. (2)

Open-Label Study to RAPID 1 (028)

The Phase III, open-label extension (OLE) study to RAPID 1 is
investigating the long-term efficacy and safety of subcutaneous CIMZIA (400
mg every 2 weeks) together with methotrexate in the treatment of signs and
symptoms and in the prevention of joint damage in patients with active RA.
Patients completing RAPID 1 through 52 weeks (completers), or who were
ACR20 nonresponders at Week 12 (confirmed at Week 14) and were to be
withdrawn from the study at Week 16 (withdrawers), could continue in the
028 study. The open-label extension study continued to evaluate the effects
of CIMZIA over two years.

FAST 4WARD (Study 011)

In the 24-week FAST 4WARD (eFficAcy and Safety of cerTolizumab pegol –
4 Weekly dosAge in RheumatoiD arthritis, Study O11) phase III study, 220
adult patients with active RA who had previously failed at least one
disease-modifying antirheumatic drugs (DMARD) were randomized to receive
either CIMZIA 400 mg subcutaneously every four weeks (n=111) or placebo
(n=109). Patients were assessed for improvement in signs and symptoms of
RA. The primary endpoint of the 011 study was ACR20 responder rate, with
secondary measures including ACR50 and ACR70 responder rates.

About Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a progressive autoimmune disease that
causes chronic inflammation of the joints. It is estimated that five
million people suffer from RA globally, with 0.3 percent to 1 percent of
the population in industrialized countries suffering from RA. It is
estimated that, approximately 1.3 million people in the United States have
RA. Women are three times more likely to be affected than men. Although it
can affect people of all ages, the onset of RA usually occurs between the
ages of 35-55.

Symptoms of RA include joint stiffness, joint pain, inflammation of the
affected areas and an associated reduction in mobility. These symptoms can
be intermittent and vary in severity from patient to patient. In more
severe cases RA can eventually lead to disability. RA patients are also at
a higher risk of developing other conditions, in particular heart disease,
stroke, infections, lung problems and osteoporosis.

As there is currently no cure for RA, treatment goals center on disease
management and controlling symptoms. Treatment is aimed at controlling
disease progression, providing pain relief and reducing swelling,
preventing joint damage and deformity and maintaining function of the
affected joints to prevent disability.

Traditional treatments for RA include nonsteroidal anti-inflammatory
drugs (NSAIDs), corticosteroids and disease-modifying antirheumatic drugs
(DMARDs), with biological therapies a more recent addition. Anti-TNF
(TNF-alpha; Tumor Necrosis Factor) therapies are specific types of
biological therapies which have been used in patients with RA. They may be
given alone but are usually given in combination with methotrexate or
another immunosuppressant. They work by inhibiting the action of TNF-alpha,
an inflammatory mediator, either directly or indirectly responsible for
damaging the joint.

About CIMZIA(R) (certolizumab pegol)

CIMZIA is the only PEGylated anti-TNF (Tumor Necrosis Factor). CIMZIA
has a high affinity for human TNF-alpha, selectively neutralizing the
pathophysiological effects of TNF-alpha. Over the past decade, TNF-alpha
has emerged as a major target of basic research and clinical investigation.
This cytokine plays a key role in mediating pathological inflammation, and
excess TNF-alpha production has been directly implicated in a wide variety
of diseases.

UCB submitted a Marketing Authorisation Application to the European
Medicines Agency in June 2008 requesting the approval of CIMZIA as a
subcutaneous treatment for adults with moderate to severe active RA. The US
Food and Drug Administration (FDA) has approved CIMZIA (certolizumab
pegol), for reducing signs and symptoms of Crohn’s disease and maintaining
clinical response in adult patients with moderate to severe active disease
who have an inadequate response to conventional therapy. CIMZIA was
approved in Switzerland for the induction of a clinical response and for
the maintenance of a clinical response and remission in patients with
active Crohn’s disease who have not responded adequately to conventional
treatment. CIMZIA is currently under review by the FDA for the treatment of
adult patients with active rheumatoid arthritis (RA). CIMZIA is a
registered trademark of UCB PHARMA S.A. Please visit ucb-group for
full prescribing information for CIMZIA.

Tuberculosis (frequently disseminated or extrapulmonary at clinical
presentation), invasive fungal infections, and other opportunistic
infections, have been observed in patients receiving CIMZIA. Some of these
infections have been fatal. Anti-tuberculosis treatment of patients with
latent tuberculosis infection reduces the risk of reactivation in patients
receiving treatment with TNF blockers such as CIMZIA. However, active
tuberculosis has developed in patients receiving CIMZIA whose tuberculin
test was negative. Evaluate patients for tuberculosis risk factors and test
for latent tuberculosis infection prior to initiating CIMZIA and during
therapy. Initiate treatment of latent tuberculosis infection prior to
therapy with CIMZIA. Monitor patients receiving CIMZIA for signs and
symptoms of active tuberculosis, including patients who tested negative for
latent tuberculosis infection. Consider anti-tuberculosis therapy prior to
initiation of CIMZIA in patients with a past history of latent or active
tuberculosis in whom an adequate course of treatment cannot be confirmed.

Serious infections, sepsis, and cases of opportunistic infections,
including fatalities, have been reported in patients receiving TNF
blockers, including CIMZIA. Infections have been reported in patients
receiving CIMZIA alone or in conjunction with immunosuppressive agents. Do
not initiate treatment with CIMZIA in patients with active infections,
including chronic or localized infections. Patients who develop a new
infection while undergoing treatment with CIMZIA should be monitored
closely. Discontinue administration of CIMZIA if a patient develops a
serious infection. Exercise caution when considering the use of CIMZIA in
patients with a history of recurrent infection, concomitant
immunosuppressive therapy, or underlying conditions that may predispose
them to infections, or patients who have resided in regions where
tuberculosis and histoplasmosis are endemic.

Use of TNF blockers, including CIMZIA may increase the risk of
reactivation of hepatitis B virus (HBV) in patients who are chronic
carriers of this virus. Some cases have been fatal. Evaluate patients at
risk for HBV infection for prior evidence of HBV infection before
initiating CIMZIA therapy. Exercise caution in prescribing CIMZIA for
patients identified as carriers of HBV. Patients who are carriers of HBV
and require treatment with CIMZIA should be closely monitored for clinical
and laboratory signs of active HBV infection throughout therapy and for
several months following termination of therapy. In patients who develop
HBV reactivation, discontinue CIMZIA and initiate effective anti-viral
therapy with appropriate supportive treatment.

During controlled and open-labeled portions of CIMZIA studies of
Crohn’s disease and other investigational uses, malignancies were observed
at a rate (95% confidence interval) of 0.6 (0.4, 0.8) per 100 patient-years
among 4,650 CIMZIA-treated patients verses a rate of 0.6 (0.2, 1.7) per 100
patient-years among 1,319 placebo-treated patients. The size of the control
group and limited duration of the controlled portions of the studies
preclude the ability to draw firm conclusions. In studies of CIMZIA for
Crohn’s disease and other investigational uses, there was one case of
lymphoma among 2,657 CIMZIA-treated patients and one case of Hodgkin
lymphoma among 1,319 placebo-treated patients. The potential role of TNF
blocker therapy in the development of malignancies is not known.

Symptoms compatible with hypersensitivity reactions, including
angioedema, dyspnea, hypotension, rash, serum sickness, and urticaria, have
been reported rarely following CIMZIA administration. If such reactions
occur, discontinue further administration of CIMZIA and institute
appropriate therapy.

Use of TNF blockers, including CIMZIA, has been associated with rare
cases of new onset or exacerbation of clinical symptoms and/or radiographic
evidence of demyelinating disease. Rare cases of neurological disorders,
including seizure disorder, optic neuritis, and peripheral neuropathy have
been reported in patients treated with CIMZIA; the causal relationship to
CIMZIA remains unclear. Exercise caution in considering the use of CIMZIA
in patients with these disorders.

Rare reports of pancytopenia, including aplastic anemia, have been
reported with TNF blockers. Medically significant cytopenia (e.g.,
leukopenia, pancytopenia, thrombocytopenia) has been infrequently reported
with CIMZIA. The causal relationship of these events to CIMZIA remains
unclear. Advise all patients to seek immediate medical attention if they
develop signs and symptoms suggestive of blood dyscrasias or infection
(e.g., persistent fever, bruising, bleeding, pallor) while on CIMZIA.
Consider discontinuation of CIMZIA therapy in patients with confirmed
significant hematologic abnormalities.

Serious infections were seen in clinical studies with concurrent use of
anakinra (an interleukin-1 antagonist) and another TNF blocker, with no
added benefit. Therefore, the combination of CIMZIA and anakinra is not
recommended.

Interference with certain coagulation assays has been detected in
patients treated with CIMZIA. There is no evidence that CIMZIA therapy has
an effect on in vivo coagulation.

Cases of worsening congestive heart failure (CHF) and new onset CHF
have been reported with TNF blockers. CIMZIA has not been formally studied
in patients with CHF. Exercise caution when using CIMZIA in patients who
have heart failure and monitor them carefully.

Treatment with CIMZIA may result in the formation of autoantibodies
and, rarely, in the development of a lupus-like syndrome. Discontinue
treatment if symptoms of lupus-like syndrome develop.

Do not administer live vaccines or attenuated vaccines concurrently
with CIMZIA.

In controlled Crohn’s clinical trials, the most common adverse events
that occurred in greater than or equal to 5% of CIMZIA patients (n=620) and
more frequently than with placebo (n=614) were upper respiratory infection
(20% CIMZIA, 13% placebo), urinary tract infection (7% CIMZIA, 6% placebo),
and arthralgia (6% CIMZIA, 4% placebo). The proportion of patients who
discontinued treatment due to adverse reactions in the controlled clinical
studies was 8% for CIMZIA and 7% for placebo.

CIMZIA should be administered by a healthcare professional.

About UCB

UCB, Brussels, Belgium (ucb-group) is a global leader in the
biopharmaceutical industry dedicated to the research, development and
commercialization of innovative medicines with a focus on the fields of
central nervous system and immunology disorders. Employing around 12 000
people in over 40 countries, UCB achieved revenue of 3.6 billion euro in
2007. UCB is listed on Euronext Brussels (symbol: UCB). UCB’s North
American headquarters is located in Atlanta, Ga.

Forward Looking statement

This press release contains forward-looking statements based on current
plans, estimates and beliefs of management. Such statements are subject to
risks and uncertainties that may cause actual results to be materially
different from those that may be implied by such forward-looking statements
contained in this press release. Important factors that could result in
such differences include: changes in general economic, business and
competitive conditions, effects of future judicial decisions, changes in
regulation, exchange rate fluctuations and hiring and retention of its
employees.

UCB
ucb-group

View drug information on Cimzia.

Make Holiday Gifts Nice, Not Naughty, By Avoiding Allergy, Asthma Triggers

It’s difficult enough to find the perfect holiday gifts for friends and loved ones, but the task becomes even trickier if they have allergies or asthma.

Fear not, shoppers the American College of Allergy, Asthma and Immunology (ACAAI) and its allergist members, doctors who are experts at diagnosing and treating allergies and asthma, offer these gift-giving tips:

– Go easy on edibles – “Food allergens lurk in all kinds of holiday treats, from fruitcake which may contain nuts, to cookies made with wheat,” said allergist Myron Zitt, MD, past-president of ACAAI. To be safe, avoid food gifts. A better bet is a gift certificate to the recipient’s favorite restaurant. Also consider non-food items sure to please any foodie such as attractive plates, serving platters or a fun kitchen gadget.

– Pause at the pet shop – Little ones may beg for a furry friend, but pet dander, saliva and urine from cats and dogs can trigger allergy and asthma symptoms which will certainly put a damper on holiday cheer. Instead, consider a hypoallergenic stuffed animal that’s machine washable. Parents, remember to wash it weekly in hot water to rid it of allergy- and asthma-triggering dust mites.

– Go for the gold – Jewelry may seem like a safe bet, but many people have a nickel allergy, frequently found in costume jewelry. If 18 karat gold is too much for your budget, consider an alternative gift like a watch with a plastic band in case the recipient is allergic to leather.

– Be cautious of clothing – A festive holiday sweater may be in style but if it’s made with angora (rabbit fur) or wool (including cashmere) your friend with itchy eczema will feel miserable rather than fashionable. If you want to give clothing, pick something made of 100 percent cotton.

– Please, no perfumes – Perfume, candles, soaps or lotions won’t pamper those who sneeze from strong scents or may even break out in a rash. Shop at stores that feature allergen free products, like health food stores, or, when in doubt, consider a department store gift certificate.

– Pass on the poinsettia – Nothing says the holidays like poinsettias, but it can mean trouble for those with a latex allergy (the plant is in the rubber tree family). Flowers in general can make people with allergies sniff and sneeze. If you insist on bestowing blooms, consider roses and orchids, which tend to be less of a problem for allergy sufferers.

Source: American College of Allergy, Asthma and Immunology (ACAAI)

Life-Saving, Low-Cost Ventilators For Emergency, Rural And Military Use Developed By Doctors

A group of UK anaesthetists have designed and tested three prototype low-cost ventilators that could provide vital support during major healthcare emergencies involving large numbers of patients or casualties. The devices, detailed in a paper published online by Anaesthesia, could also be used where resources are limited, such as in developing countries, remote locations or by the military.

“Our research has demonstrated that it is possible to make a gas-efficient ventilator costing less than ??200, for use where 2-4 bar oxygen is available, with no pressurised air or electrical requirements” says consultant anaesthetist Dr John Dingley from Morriston Hospital, Swansea.

“Such a device could be mass-produced for crises where there is an overwhelming demand for mechanical ventilation and a limited oxygen supply.”

Problems with limited oxygen supply date back to the First World War when medical professionals had to deal with the large numbers of casualties affected by poison gas.

“The physiologist J S Haldane developed a delivery system that provided a high flow of oxygen from a modest fresh gas flow” says Dr Dingley, who is also a Reader in Anaesthetics at Swansea University.

“Modern equipment has become so sophisticated that we have, in some ways, lost sight of the basic principles that can be adopted in emergency healthcare situations.

“So our aim was to extend Haldane’s concept of maximally efficient oxygen delivery to include pneumatic gas-powered ventilator designs.

“The initial design was envisaged as a ventilator for difficult environments, especially military scenarios, where large oxygen cylinders would be impractical, or in short supply, and electrical power would be unavailable.

“This led to two variants that are suited to emergency construction in bulk for mass deployment prior to a respiratory failure pandemic or other major healthcare situation.”

All three designs operate on the principle that the energy is taken from approximately 1 l.min-1 compressed oxygen at a supply pressure of 2-4 bar to provide the motive force to ventilate the lungs.

“After the stored energy has been used to provide motive power in this way, the waste oxygen – which is now at atmospheric pressure – is then re-used to enrich the air being drawn into the ventilator before it is delivered to the lungs” explains Dr Dingley.

“In this way, most of the breathable oxygen is obtained from ambient air.”

A mechanical test lung was used to test the three devices and this showed that they would provide effective ventilation for patients who were unable to breathe unaided. The devices were also tested over a range of lung volumes and compliances, which indicated that the oxygen consumption was considerably lower than that of the commercially available gas powered ventilators currently on the market.

This means that even if the devices had to be used over an extended period of time, they would use less than conventional units. They would also provide a viable and financially attractive alternative to buying extra critical care ventilators, which are expensive, complex microprocessor-driven devices.

“These devices could be used anywhere that 2-4 bar oxygen is available, such as a converted ward with no piped air or electricity” says Dr Dingley. “In extreme circumstances, they could even run on hospital compressed air, using very little air from the hospital’s compressor reservoir.

“The concept, although unconventional, also allows an attending staff member to take over manual ventilation of the patient, with air if necessary, if a hospital’s pneumatic mechanism or gas supply fails.

“The mechanism could possibly be made as a single-use device and stockpiled for crises where there is an overwhelming demand for mechanical ventilation, such as a pandemic.”

Dr Dingley points out that major healthcare emergencies can call for creative solutions and that these can often be unorthodox.

For example during the 1952 Copenhagen polio epidemic, relays of medical students manually ventilated the lungs of patients with tracheostomies under the guidance of the anaesthetist. And in Beijing in 2003, trainees from unrelated specialties found themselves managing a sealed intensive therapy unit filled with avian flu victims, while receiving clinical guidance from overseas experts via a mobile phone.

“Health services are not designed to cope with the most extreme situations and fast, easy solutions can quite literally save lives” says Dr Dingley. “We feel that the low oxygen consumption pneumatic ventilators we have designed and tested could provide a low-cost, speedy solution in a crisis. They could also be used for a wide range of applications, such as rural healthcare and armed conflicts.”

The paper, which is available online, contains full technical details of the three devices and the testing process, together with photographs and diagrams.

A low oxygen consumption pneumatic ventilator for emergency construction during a respiratory failure pandemic. Williams et al. Anaesthesia. Publication online ahead of print. (January 2010). DOI: 10.1111/j.1365-2044.2009.06207.x

Source:
Annette Whibley
Wiley-Blackwell

EU Asks Libya To Recall Death Sentences Of 6 Health Workers

After five Bulgarian nurses and one Palestinian doctor have been sentenced to death by a Libyan court for allegedly infecting about 400 children with HIV on purpose, Benita Ferrero-Waldner, EU commissioner for Foreign Relations and Neighborhood Policy has urged Libya to recall the sentences.

Benita Ferrero-Waldner wrote to the European Affairs Secretary, Libya, urging him to annul the death sentences, according to the Sofia News Agency, Bulgaria.

The mystery and shocking inaccuracy surrounding this trial beggars belief:

1. There is clear evidence that the children were already infected with HIV before the 6 health workers ever set foot on Libyan soil. The courts have refused to look at this evidence on two occasions. Eminent international scientists could have presented this evidence had the Libyan courts allowed them to do so.

2. There is compelling evidence that the hospital where the 6 medical workers were supposed to have infected the children had shocking hygiene practices. 114 Nobel Prize laureates asked Colonel Gaddafi, Libya’s leader, to accept the evidence. He didn’t.

From what I can make out, this trial has chosen to blatantly ignore important evidence that shows the 6 medical workers are not guilty. This is a cover-up. The 6 medical workers, the 400 infected children and their families, plus people who will become infected in future because of appalling hygiene standards in the hospital, will pay the price. The wrong people are being punished while the guilty are not. The whole thing stinks to high heaven!!

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The Molecular Power Behind Memory

Neuroscientists have long wondered how individual connections between brain cells remain diverse and “fit” enough for storing new memories. Reported in the prestigious science journal Neuron, a new study led by Dr. Inna Slutsky of the Sackler School of Medicine at Tel Aviv University describes what makes some memories stick.

The key is GABA (??-Aminobutyric acid), a natural molecule that occurs in the brain, which could be the main factor in regulating how many new memories we can generate, the new study has found. The understanding of these mechanisms might lead to the development of new memory enhancers and new treatments for neurodegenerative diseases such as Alzheimer’s.

Memories, Dr. Slutsky says, are stored in synaptic connections between neurons in our brain. In the past, other teams, including her own, have demonstrated that the strength of individual synapses is highly variable, even at the single neuron level. This variability ultimately determines if and how new memories are stored, and the key to this variability is GABA, a naturally-occurring chemical found in the brain.

Tight connections and lone rangers

Dr. Slutsky’s graduate student Tal Laviv and postdoctoral fellow Inbal Riven, the lead authors in the study, applied advanced nanotechnology methods in optical imaging to track how proteins engineered by Prof. Paul Slesinger and his team at The Salk Institute interact with GABA at the single-synapse level.

In the hippocampus, one of the main areas of the brain involved in learning and memory, the strength of neuronal connections is known to be highly variable. Some neurons are tightly connected to others, while some appear to be “lone rangers.”

The new paper, which examines individual synapses in the hippocampus, demonstrates that this process is regulated by GABA, the main inhibitory neurotransmitter in our brain. “We determined that variations in the local level of GABA in the vicinity of individual synapses are responsible for the differences or ‘heterogeneity’ of synaptic strength. And this heterogeneity may facilitate the formation of new memories,” Dr. Slutsky explains.

Looking at the brain at rest

While looking at the brain in its basal state – when the activity was “at rest” before attempting to memorize a list of items or after a memory had been stored – Dr. Slutsky’s team could actually “see” where synapses differ at different dendritic branches in the neuronal network. Those branches of neurons close to a cell body displayed a larger number of weak synapses, while the most distant branches were composed of a smaller number of strong synapses.

“Why the difference?” they asked. GABA was the answer. Higher concentrations of GABA near a synapse induced a stronger activation of its receptors, weakening basal synapse strength. As a result, GABA makes this synapse more liable to the formation of new memories, the researchers propose.

Dr. Slutsky, who previously discovered a basal-state regulator molecule, says that the research may also have implications for treating diseases of the mind. “We found that amyloid-beta, a well-known hallmark of Alzheimer’s disease, regulates basal synapse strength in an opposite way to GABA,” she notes, suggesting that an increase in the basal activity of synapses may initiate memory decline in Alzheimer’s and other neurodegenerative disorders.

Experiments in the study were done using neuronal cultures and brain slices of rats subjected to molecular biology, optical imaging and electrophysiological techniques. The study also constituted a technical achievement, since it used advanced imaging techniques such as fluorescence resonance energy transfer (FRET) spectroscopy that looked at protein-to-protein interactions in the brain at the 10 nanometer scale. In the past, such fine resolution was impossible – brain scientists could only investigate interactions at the level of entire tissues, not between molecules at individual synapses.

Source:
George Hunka

American Friends of Tel Aviv University

New Evidence Shows MabThera Inhibits Joint Damage In Patients With Rheumatoid Arthritis

New data presented at the EULAR meeting (European League Against Rheumatism) show for the first time that MabThera (rituximab), a unique B cell targeted therapy, is able to significantly inhibit structural damage of joints caused by rheumatoid arthritis (RA). The study was conducted in patients who had an inadequate response to one or more TNF inhibitors and they received either MabThera plus methotrexate (MTX) or MTX alone. X-ray evidence at 56 weeks showed that the progression of bone erosions and progression of narrowing of joint spaces in patients in the MabThera group were reduced by more than 50 % compared to patients receiving MTX alone (erosion scores of 0.59 and 1.32 respectively; joint space narrowing scores of 0.41 and 0.99 respectively).

Damage to the structure of the joints ultimately causes destruction of the joints and contributes to joint deformity and loss of mobility. Patients’ ability to work and perform every day tasks such as getting dressed, walking and eating can be severely hampered.

Presenting the results, Professor Keystone, Rheumatology Department at the University of Toronto, Canada, said: “This is the first evidence demonstrating that MabThera can inhibit structural joint damage in patients with an inadequate response to one or more TNF inhibitors. Preventing structural damage is a critical outcome in treating rheumatoid arthritis. These X-ray data confirm MabThera as an effective and innovative therapy for patients with rheumatoid arthritis and highlight the value of targeting B cells.”

Repeat treatment courses
Additional new data presented at EULAR demonstrate that repeat courses of MabThera in RA patients, 6 to 12 months after the initial course, provide continued improvement of symptoms across all clinical measures. Each treatment course consists of two infusions of 1000mg given two weeks apart. The challenging goal of treatment in RA is remission and, following a second course of MabThera in patients with an inadequate response to one or more TNF inhibitors, the number of patients achieving remission doubled from 6 % following an initial course to 13 % following a second course. A similar trend was seen for those achieving the hard-to-reach goal of a 70 % improvement in symptoms (ACR70), with responses increasing from 12 % following an initial course to 21 % following a second course.

Patient perspectives
Importantly, data presented at EULAR show improvements in clinical scores are reflected in patient reported outcomes.

“While it is important to a physician to address a disease from a clinical perspective, what matters most to the patient is whether they are able to function normally and how well they feel. For example, the impact of fatigue is often underestimated, but this is something which really impacts patients’ lives. MabThera has demonstrated continuous improvements in physical and mental health aspects with repeated courses of therapy”, said Professor Tak, Director, Division of Clinical Immunology and Rheumatology at the Academic Medical Centre/University of Amsterdam, The Netherlands.

Approval Status
On 2 June 2006 MabThera received a recommendation for approval from the Committee for Medicinal Products for Human Use (CHMP) for the treatment of rheumatoid arthritis (RA) in Europe. MabThera, in combination with methotrexate, has been recommended for the treatment of adult patients with severe active rheumatoid arthritis who have had an inadequate response or intolerance to other disease-modifying anti-rheumatic drugs (DMARDs). On 28 February 2006, after priority review, Genentech and Biogen Idec received US approval for Rituxan (rituximab in the US) for the treatment of adult patients with moderately to severely active RA in combination with methotrexate for reducing signs and symptoms in those RA patients who have had an inadequate response to one or more tumour necrosis factor (TNF) therapies.

About the REFLEX study
The REFLEX study (Randomised Evaluation oF Long-term Efficacy of MabThera in RA) is a multi-centre, randomized, double-blind, placebo-controlled Phase III study. In this trial, patients who received a single course of only two infusions of MabThera with a stable dose of methotrexate (MTX) displayed a statistically significant improvement in symptoms measured at 24 weeks, compared to those receiving placebo and MTX. Patients receiving additional courses did so between 6 and 12 months after the initial course. Consistent with previous findings, analysis of the REFLEX 56-week data did not reveal any unexpected safety signals. The companies continue to monitor the long-term safety of rituximab in all clinical trials.

A further phase III development programme for MabThera therapy in patients with rheumatoid arthritis who have had an inadequate response to disease modifying anti-rheumatic drugs (DMARDs) is ongoing.

Long term safety and repeated courses
Further new data of a pooled analysis presented at EULAR confirmed the safety profile of rituximab identified in the original randomised clinical trials. The analysis included all RA patients treated with MabThera during clinical development which amounted to over 1,600 patient years with some patients being followed for over 3 years, many of whom had received multiple courses of treatment. This analysis did not reveal any unexpected safety signals.

About MabThera in rheumatoid arthritis
MabThera selectively targets a subset of B cells that express CD20, leaving stem, pro-B and plasma cells unaffected. This subset of B cells plays a key role in the autoimmune process of RA and MabThera aims to interrupt this process by inhibiting a series of reactions inflaming the synovia and leading to cartilage loss and bone erosion that is characteristic of the disease. More than 1,000 patients with RA have been treated with MabThera in clinical trials to date. A comprehensive Phase III clinical development programme is also currently underway to further investigate the potential clinical benefit of MabThera in earlier RA.

About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2005, sales by the Pharmaceuticals Division totalled 27.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.2 billion Swiss francs. Roche employs roughly 70,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet (roche/).

All trademarks used or mentioned in this release are legally protected.

For further information:
-About EULAR: eular/
-British Society for Rheumatology: rheumatology/
-American College of Rheumatology: rheumatology/
-About Genentech: gene/
-About BiogenIdec: biogenidec/

Media Relations Contacts:
- Baschi D?rr
- Alexander Klauser
- Daniel Piller (Head Roche Group Media Office)
- Katja Prowald (Head R&D Communications)
- Martina Rupp

Contact: Basel Media Office
European League Against Rheumatism

View drug information on Rituxan.

The White House Announces H1N1 Flu Preparedness Summit

The White House announced that Health and Human Services Secretary Kathleen Sebelius, Homeland Security Secretary Janet Napolitano, Education Secretary Arne Duncan, and Homeland Security Advisor John Brennan will host an all-day H1N1 Flu Preparedness Summit with states to further prepare this nation for the possibility of a more severe outbreak of H1N1 flu. The Summit will be held on July 9, 2009 at the Natcher Conference Center at the National Institutes of Health in Bethesda, Maryland.

WHO

Kathleen Sebelius, HHS Secretary
Janet Napolitano, DHS Secretary
Arne Duncan, Education Secretary
John Brennan, National Security Advisor

WHAT

H1NI Flu Preparedness Summit

WHEN

Thursday, July 9, 2009 at 8:30 a.m.

WHERE

Natcher Conference Center Auditorium (Bldg. 45)
National Institutes of Health
9000 Rockville Pike
Bethesda, Md. 20892

The H1N1 flu virus continues to circulate in this country and in at least 100 other countries around the world – especially in the Southern Hemisphere, where flu season is underway.

“Scientists and public health experts forecast that the impact of H1N1 may well worsen in the fall – when the regular flu season hits, or even earlier, when schools start to open – which is only five or six weeks away in some cases,” Secretary Sebelius said. “The goal of the Summit is to launch a national influenza campaign by bringing federal, state and local officials, emergency managers, educators and others together with the nation’s public health experts to build on and tailor states’ existing pandemic plans, share lessons learned and best practices during the spring and summer H1N1 wave, and discuss preparedness priorities.”

“The federal government remains vigilant and well coordinated with state, local, and international partners as we prepare for all possibilities as to how the H1N1 flu virus may impact us this fall,”said Secretary Napolitano.

“Prevention is everyone’s business. Parents, children, teachers, school leaders, communities, government and businesses, we need do our part individually and collectively prevent the spread of the flu virus,” said U.S. Secretary of Education Arne Duncan. “We are emphasizing safety and the need to continue learning. We will continue following guidance from the Centers for Disease Control and Prevention and encouraging schools and districts to be in close communication with their local public health authorities and political leadership.”

Source
The Office of Minority Health

Inappropriate prescribing of antibiotics by NPs and MDs continues

Both nurse practitioners and physicians are prescribing inappropriate antibiotics to patients with viral upper-respiratory tract infections, a practice that may lead to increased rates of antimicrobial resistance. Researchers also found that highly marketed broad-spectrum antibiotics are being prescribed excessively, by both NPs and MDs, to patients with diagnoses of viral illnesses. It is well accepted that antibiotics have no clinical effect in the treatment of these illness.

The study, published in the Journal of the American Academy of Nurse Practitioners, further found that antibiotic prescribing by nurse practitioners to patients with Medicaid insurance was more appropriate than that of physician prescribing for the same category of patients. This may suggest a difference in response, by NPs, to patient demand among this population and/or a keener awareness among NPs of the budget constraints that are affecting state Medicaid programs.

According to the study, increased adherence, especially by nurse practitioners, to well accepted clinical guidelines and involvement in system-based quality assurance programs are needed to decrease this excessive use of antibiotics.

This study is published in the October issue of the Journal of the American Academy of Nurse Practitioners . Media wishing to receive a PDF of the article, please contact medicalnewsbos.blackwellpublishing.

About the Journal

Journal of the American Academy of Nurse Practitioners (JAANP) is a peer-reviewed professional journal that serves as the official publication of the American Academy of Nurse Practitioners. Published since 1989, the JAANP is designed to serve the needs of nurse practitioners and other health care professionals who have a major interest in primary health care. The JAANP publishes timely original, peer-reviewed articles addressing clinical practice, clinical management, health policy, research, education and other issues affecting nurse practitioners and other primary health care providers.

About Blackwell Publishing

Blackwell Publishing is the world’s leading society publisher, partnering with more than 600 academic and professional societies. Blackwell publishes over 750 journals annually and, to date has published close to 6,000 text and reference books, across a wide range of academic, medical, and professional subjects.

Sharon Agsalda
medicalnewsbos.blackwellpublishing
781-388-8507
Blackwell Publishing Ltd.
blackwellpublishing

Promising Hormone Treatment For Alzheimer’s Disease And Stroke

Saint Louis University researchers have identified a novel way of getting a potential treatment for Alzheimer’s disease and stroke into the brain where it can do its work.

“We found a unique approach for delivering drugs to the brain,” says William A. Banks, M.D., professor of geriatrics and pharmacological and physiological science at Saint Louis University. “We’re turning off the guardian that’s keeping the drugs out of the brain.”

The brain is protected by the blood-brain barrier (BBB), a gate-keeping system of cells that lets in nutrients and keeps out foreign substances. The blood-brain barrier passes no judgment on which foreign substances are trying to get into the brain to treat diseases and which are trying to do harm, so it blocks them without discrimination.

“The problem in treating a lot of diseases of the central nervous system – such as Alzheimer’s disease, HIV and stroke – is that we can’t get drugs past the blood-brain barrier and into the brain,” says Banks, who also is a staff physician at Veterans Affairs Medical Center in St. Louis.

“Our new research shows a way of getting a promising treatment for these types of devastating diseases to where they need to be to work.”

The therapy – known as PACAP27 – is a hormone produced by the body that is a general neuro-protectant. PACAP stands for pituitary adenylate cyclase-activating polypeptide. “It is a general protector of the brain against many types of insult and injury,” Banks says.

He compares a specific guarding mechanism in the BBB – efflux pumps – to bouncers at exclusive nightclubs. While they welcome those on the approved guest list, they look for trouble-makers trying to crash the party, refuse to let them in and evict them if they do get in.

The scientists isolated the particular gatekeeper than evicts PACAP27. Then they designed an antisense, a specific molecule that turned off the impediment.

“We went after the guard and essentially told him to go on break for a while so PACAP27 could get into the brain,” Banks says.

They used mouse models of Alzheimer’s disease and stroke to test what would happen if PACAP27 could get into the brain.

“We reversed the symptoms of the illnesses,” Banks says. “The mice that had a version of Alzheimer’s disease became smarter and in the stroke model, we reduced the amount of damage caused by the blockage of blood to the brain and improved brain recovery.”

Simply turning off the gatekeeper that kept PACAP27 out of the brain allowed enough of the hormone that already is in the body to get inside the brain, where it effectively treated strokes. However, the mice that had a version of Alzheimer’s disease needed both an extra dose of PACAP27 and the antisense that turned off the gatekeeper to improve learning.

“These findings are significant for three reasons. We have found a therapy that reverses symptoms of Alzheimers’s disease and stroke in a mouse model. We have isolated the particular roadblock that keeps the treatment from getting into the brain. And we have found a way to finesse that obstacle so the medicine can get into the brain to do its work,” Banks says. “This could have implications in treating many diseases of the central nervous system.”

The findings were published in the Nov. 12 early online issue of the Journal of Cerebral Blood Flow & Metabolism.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first M.D. degree west of the Mississippi River. Saint Louis University School of Medicine is a pioneer in geriatric medicine, organ transplantation, chronic disease prevention, cardiovascular disease, neurosciences and vaccine research, among others. The School of Medicine trains physicians and biomedical scientists, conducts medical research, and provides health services on a local, national and international level.

Source: Nancy Solomon

Saint Louis University