Surgeons performing operations to remove patients’ prostate glands — the primary treatment for prostate cancer — go through a steep learning curve, according to a study published online July 24 in the Journal of the National Cancer Institute. As the surgeons gain more experience performing the operation, called a radical prostatectomy, the chance that patients’ prostate cancer will reoccur goes down.

The idea that more experienced surgeons perform more successful surgeries is a widely held belief. But there have been few data to support this idea, and it has not been previously shown whether a surgeons’ experience makes a large or small difference on their patients’ outcome.

Andrew Vickers, Ph.D., of Memorial Sloan-Kettering Cancer Center in New York and colleagues analyzed data from 72 surgeons at four institutions and 7,765 of their prostate cancer patients treated with radical prostatectomies between 1987 and 2003. They measured surgeons’ experience by the number of times they had performed the procedure before each operation.

More surgical experience was associated with a greater likelihood that the patient’s cancer would not return after their operation. The learning curve for this procedure was very steep — there was dramatic improvement in patient outcomes as surgeons’ experience increased up to 250 operations, after which increasing experience had little influence on cancer recurrence. Patients treated by inexperienced surgeons (for example, those with 10 prior operations) were nearly 70% more likely to have evidence of recurrence of their prostate cancer within five years than those whose surgeons had performed 250 operations (17.9% vs. 10.7%).

“Our findings also have implications for education in surgical oncology. Although the successful practice of surgery necessarily presumes a lifetime of learning, the large number of cases required before the learning curve plateaus suggests the need to expand opportunities for training in surgical technique for surgeons in the early years after residency training,” the authors write.

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UCSF physicians are combating a devastating side effect of chemotherapy with an innovative new program — “Hair to Stay” — to evaluate devices that could reduce scalp hair loss in breast cancer patients.

One feasibility study on a scalp cooling system, the first significant inquiry of its kind in the United States, will test the safety and effectiveness of a device already widely used overseas called the “DigniCap.” The FDA recently approved a pilot study of the Swedish cool cap, which continuously cools a patient’s scalp during treatment using a circulating coolant inside a gel cap. The first patients are being enrolled at the UCSF Helen Diller Family Comprehensive Cancer Center and at Wake Forest University Medical Center.

“Devices that prevent hair loss have the potential to make a huge difference to our patients,” said Laura Esserman, MD, MBA, co-leader of the Breast Oncology Program at the center and director of the UCSF Carol Franc Buck Breast Care Center. “If we can avoid hair loss, then our patients can avoid one of the most emotionally difficult and dreaded side effects of chemotherapy.”

The cool cap process is a relatively simple and low-cost solution. By cooling the scalp, blood vessels surrounding the hair roots contract, resulting in a significant reduction of cytotoxins to the follicle. With reduced blood flow, less chemotherapy is available for cell uptake, while at the same time the lower temperature results in less absorption of the chemicals.

UCSF breast cancer patients ineligible for the FDA DigniCap trial have other scalp-cooling options. As part of another study evaluating patient experience, the university has purchased a freezer for cold caps, allowing patients to bring in their own caps and keep them cooled during chemotherapy. Currently, patients who provide caps go through as many as a dozen during a treatment session — the caps heat up in as little as 20 minutes.

Chemotherapy-caused hair loss takes a profound physical and psychological toll on cancer patients and is considered one of the most feared and traumatic side effects of cancer treatment.

“Almost all standard chemotherapy treatments for early stage breast cancer cause hair loss,” said Hope S. Rugo, MD, principal investigator for the study and director of Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center.

“Every day, I sit across from women with a breast cancer diagnosis for whom the inevitability of losing their hair is a painful and emotionally distressing prospect. By helping to identify devices that can reduce hair loss, we have the potential to impact patients’ quality of life.”

Historically, Rugo said, cooling systems and cold caps have not been used in the United States because of concerns that the scalp cooling could allow cancer cells to hide in the scalp. But, Rugo said, “the incidence of scalp metastases in breast cancer is extremely low and we are carefully following patients using these systems.”

The goal of the new feasibility study – the first step toward FDA product approval – is to test how well patients tolerate the device, invented in the 1990s by a Swedish oncology nurse.

In the study, a tight-fitting silicone cap is placed directly on the head; an outer neoprene cap is placed on top to insulate and secure the inner cap. Both are connected to a cooling and control unit with touch screen controls. A coolant circulates throughout the inner silicone layer, delivering consistent cooling to the entire scalp.

Following the feasibility study of 20 patients, a larger study of 100 patients is planned, an example of UCSF’s commitment toward accelerating the translation of cutting-edge research into advances in patient care.

According to research by Dignitana, makers of the DigniCap system, 8 out of 10 women in Europe and Asia who used the company’s cap cooling system during chemotherapy retained their hair.

“The DigniCap system has been extremely well received in clinical trials at leading medical centers around the world,” said Chief Executive Officer Martin Waleij. “We are very pleased that UCSF is conducting this test so that cancer patients in the United States might benefit as well.”

“Hair to Stay” is being funded by the Laszlo N. Tauber Family Foundation with a goal of mitigating trauma, maintaining dignity and restoring self-esteem to cancer patients.

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The beneficial effects of a widely used class of antidepressants might be the result of increased nerve-fiber growth in key parts of the brain, according to a Johns Hopkins study being published in the January 2006 issue of the Journal of Neurochemistry.

The study on rats, led by Vassilis E. Koliatsos, M.D., a neuropathologist at the Johns Hopkins University School of Medicine, found that selective serotonin reuptake inhibitors (SSRIs) increase the density of nerve-impulse-carrying axons in the frontal and parietal lobes of the neocortex and part of the limbic brain which control the sense of smell, emotions, motivation, and organs that work reflexively such as the heart, intestines and stomach. “It appears that SSRI antidepressants rewire areas of the brain that are important for thinking and feeling, as well as operating the autonomic nervous system,” said Koliatsos.

Axons are long, filament-shaped extensions of neurons that, together with myelin, are the main constituents of nerves. Axons conduct chemically driven nerve impulses away from the cell body toward a narrow gap known as a synapse. Among the chemicals involved are such monoamines as norepinephrine and serotonin, which, at the synapse, are transferred to another neuron.

Antidepressants, such as Prozac, Zoloft and Paxil, have long been thought to exert their clinical effects by increasing synaptic concentrations of serotonin and norepinephrine, enhancing or stimulating their transference.

“But our findings — that serotonin reuptake modulators increase the density of nerve synapses, especially in the front part of the brain – may offer a better explanation of why antidepressants are effective and why they take time to work,” according to Koliatsos.

For example, antidepressants increase synaptic monoamines within hours, and the regulatory effects on receptors are complete within a few days, yet clinically meaningful results from antidepressants usually require a two- to four-week delay.

“This disparity between simple pharmacological effects and clinical experience might be due to the time it takes for serotonin axons to grow,” Koliatsos said.

“For the patient, this hypothesis provides more tangible evidence of a real effect in the brain,” he added.

In the Hopkins study, Koliatsos and his team gave either the selective serotonin reuptake inhibitor fluoxetine (Prozac), the selective serotonin reuptake enhancer tianeptine (a drug approved only for human use in France) or the selective norepineprine reuptake inhibitor desipramine, a so-called tricyclic antidepressant, to groups of rats for four weeks and studied anatomical patterns of serotonin stimulation on various parts of the brain. The results showed that fluoxetine and tianeptine, but not desipramine, increased the density of serotonin axons in the frontal and parietal neocortex and certain limbic cortical and subcortical areas.

One possible explanation for this action is the brain-derived growth factor (BDNF). BDNF is regulated by levels of serotonin and is known to be a prime candidate for causing serotonin axon growth, Koliatsos said.

In general, the relationships between brain serotonin concentrations and BDNF expression are very complex, but previous studies have suggested that both higher (such as caused by serotonin reuptake inhibitors) and lower (such as effected by tianeptine) concentrations of free serotonin might induce BDNF expression in such brain regions as the frontal and parietal cortex.

The researchers caution that since a previous study failed to show a correlation between tianeptine treatment and BDNF levels, further investigation of the complex regulations of BDNF by antidepressants is needed.

Funding for this study came from the National Institute of Mental Health.

The study is currently available at the Journal of Neurochemistry Web site:
blackwellpublishing/journal.asp?ref=0022-3042

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View drug information on Paxil CR; Prozac Weekly; Zoloft. Continue reading →

The human papillomavirus vaccine Gardasil appears safe and effective at preventing anal cancer in young men and women, an FDA advisory panel said on Wednesday, the AP/Bloomberg Business Week reports (AP/Bloomberg Business Week, 11/17). FDA will consider the panel’s recommendation as it weighs whether to expand Gardasil’s approval to include prevention of anal cancer (Richwine, Reuters, 11/17). Gardasil already is approved for girls and women ages nine to 26 to prevent genital warts and cervical cancer, as well as boys and men of the same age to prevent genital warts (AP/Bloomberg Business Week, 11/17).

Most advisory panel members said Gardasil was shown effective in studies conducted by its manufacturer, Merck (Reuters, 11/17). The panel based its decision largely on a clinical trial involving more than 4,000 men, 15% of whom were men who have sex with men, who have an elevated risk for anal cancer. Three percent of MSM who received Gardasil developed anal lesions or anal cancer, compared with 12% of MSM in the placebo group. Overall, Gardasil was 78% effective at preventing anal lesions and 75% effective at preventing anal cancer associated with HPV.

Merck did not submit data on the vaccine’s effectiveness in women. The FDA panel said there is no reason to think Gardasil would be less effective at preventing anal cancer in women, Shelly Burgess, an FDA spokesperson, said (Walker, MedPage Today, 11/17).

Merck spokesperson Pam Eisele said a decision on the company’s application is expected by the end of the year. She added that FDA also is expected to rule on the vaccine’s use to prevent cervical cancer in women ages 27 to 45 (Reuters, 11/17).

Reprinted with kind permission from nationalpartnership. You can view the entire Daily Women’s Health Policy Report, search the archives, or sign up for email delivery here. The Daily Women’s Health Policy Report is a free service of the National Partnership for Women & Families.

© 2010 National Partnership for Women & Families. All rights reserved.

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The American Diabetes
Association (ADA) announced that securing sufficient funding for diabetes
research and prevention efforts will be its top priority for the incoming
Congress, after the 109th Congress adjourned without passing a new budget.
The decision by the 109th Congress to adjourn earlier this month without
passing a budget for Fiscal Year 2007 means that the Bush Administration’s
proposed $11 million cut to diabetes research at the National Institutes of
Health (NIH) and further cuts to prevention and treatment efforts at the
Centers for Disease Control and Prevention (CDC) were not enacted. However,
maintaining Fiscal Year 2006 funding levels also means that the federal
investment in fighting diabetes continues to fall far short of what’s
necessary to reverse the national surge in diabetes prevalence and related
complications. ADA has urged Congress to increase diabetes research at NIH
by $92 million – or 5 percent – and diabetes treatment and prevention
efforts at CDC by $20.8 million, or one dollar for every American with
diabetes.

“Congress still needs to step up to the plate and recognize the
tremendous national need to support diabetes research and prevention
efforts,” said Larry Deeb, MD, President-Medicine & Science, American
Diabetes Association. “Diabetes is growing rapidly in the United States,
but the Administration and the 109th Congress has failed to invest in
exciting research and effective treatment and prevention efforts. To stem
the tide of the diabetes epidemic, the new Congress must make the
commitment to increase federal funding for efforts that can lead toward a
cure and widespread prevention.”

Recent studies have raised the need for action from the Administration
and Congress to address the startling growth of diabetes. While nearly 21
million children and adults in the U.S. live with diabetes today, the
Centers for Disease Control and Prevention estimates that if present trends
continue, one in three Americans and one in two minorities born in 2000
will develop diabetes in their lifetime. In 2002, one in 10 healthcare
dollars went towards diabetes care. The cost of diabetes in America in 2002
was at least $132 billion.

Throughout the year, ADA volunteers urged their elected officials to
confront the diabetes epidemic. In addition to increasing funding for NIH
and CDC, ADA urged Congress to pass legislation to expand federally-funded
embryonic stem cell research and to help ensure affordable, quality
diabetes health coverage.

In May, Association volunteers played a critical role in the defeat in
the U.S. Senate of the “Health Insurance Marketplace Modernization Act”
(S.1955), legislation that would have eliminated diabetes coverage
guarantees for medications, supplies, and education vital to managing the
disease. ADA continued to oppose attempts to reconsider similar legislation
before the end of session that would have the effect of limiting crucial
coverage protections for people with diabetes.

ADA volunteers were also at the forefront of the effort to pass, in the
U.S. Senate, the Stem Cell Research Enhancement Act (H.R. 810). Top
researchers, including those at the ADA, believe embryonic stem cell
research offers great hope for a cure and better treatments for diabetes,
and ADA hopes similar legislation is reconsidered in the new Congress.

“Diabetes is the great public health crisis of the 21st century,” said
Darlene Cain, Chair of the American Diabetes Association. “There are
bipartisan solutions to this grave situation, but we need to see more
leadership from Washington to see them implemented. We look forward to
working with the Administration and the new Congress to make fighting
diabetes a priority in 2007.”

The American Diabetes Association is the nation’s leading voluntary
health organization supporting diabetes research, information and advocacy.
The Association’s advocacy efforts include helping to combat discrimination
against people with diabetes; advocating for the increase of federal
diabetes research and programs; and improved access to, and quality of,
healthcare for people with diabetes. The Association’s mission is to
prevent and cure diabetes and to improve the lives of all people affected
by diabetes. Founded in 1940, the Association provides service to hundreds
of communities across the country. For more information please call the
American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit
diabetes. Information from both these sources is available
in English and Spanish.

American Diabetes Association
diabetes Continue reading →

Pharmaceutical company Novo Nordisk’s decision to pull its Mixtard 30 insulin drug from the UK could add ??9 million to the NHS drugs bill in England alone, says an editorial in the Drug and Therapeutics Bulletin (DTB) (a BMJ publication).

The decision could also leave thousands of patients dependent on others to help them take their insulin, says DTB, which today launches its “Don’t Drop Mixtard 30″ campaign to convince the company to change its mind.

In late June Novo Nordisk announced its intention to withdraw its only conventional human biphasic insulin, Mixtard 30, from the UK market by the end of the year, citing commercial reasons.

The move will affect an estimated 90,000 patients across all age groups with type 1 and 2 diabetes who require insulin treatment.

Guidelines on the care of patients with diabetes, including those issued by the National Institute for Health and Clinical Excellence (NICE), recommend human biphasic insulin as the treatment of choice for these groups.

There are alternative biphasic analogue insulins, but these are all more expensive.

“Assuming a direct swap to Novo Nordisk’s analogue biphasic insulin, NovoMix 30, the increased prescribing costs could be over ??9 million in England alone,” says DTB.

“This is quite apart from the extra resources needed to review patients, to discuss and decide on alternative treatments, and the disruption and concern such changes may cause for affected individuals,” it continues.

The decision also means that biphasic insulin will no longer be available in the ergonomic InnoLet device, which “could therefore leave many users who have poor eyesight or reduced manual dexterity, dependent on others for their insulin administration,” adds DTB.

Furthermore, the published evidence shows that the alternative biphasic analogue insulins are no better than conventional human biphasic insulins in terms of their effectiveness, long term outcomes, or safety, it says.

But Novo Nordisk’s biphasic analogue insulin is prescribed 50% more often than Mixtard 30, it points out, possibly because it comes in a particularly convenient pen format (FlexPen).

“It is possible that the decline in Mixtard 30 sales..uld have been prevented if it had also been available in the FlexPen,” comments DTB, adding that the drug is available in this format in Germany, where there do not seem to be any plans to withdraw it.

“My personal experience is that patients prefer the FlexPen for their biphasic insulin. It’s very easy to use,” comments DTB editorial board member and consultant endocrinologist at Imperial College London, Dr Wing May Kong, in an accompanying podcast.

“It makes me wonder to what extent this drift from conventional to analogue insulin is device driven,” she asks, adding that German healthcare professionals lobbied for conventional insulin to be available in the FlexPen.

Cathy Moulton, a care advisor for Diabetes UK, says in the podcast that the charity remonstrated with Novo Nordisk about its plans. The charity was “very disappointed” by the company’s stance, particularly the short time

frame for the planned change, she said. The move “takes away patient choice,” she added.
Commenting on the plans, DTB editor, Dr Ike Iheanacho said: “The decision to remove Mixtard 30 will cause huge disruption and anxiety for people with diabetes, not least because it might take months to switch successfully to another form of insulin.”

He continued: “And at a time of tight budgetary constraint, the added costs inherent in this move are an unwelcome blow for the NHS.”

DTB has set up an online petition to protest Novo Nordisk’s decision. “We urge all those with an interest in cost effective prescribing to campaign with us against Novo Nordisk’s short-sighted decision,” it says.

Click here to listen to the podcast.

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A recent review in Faculty of 1000 Medicine Reports, a publication in which clinicians highlight advances in medical practice, suggests regional pain relief could be used during abdominal surgery. In this review, Michael Schaefer recommends a new approach that can be performed without the need for general anaesthetics.

Currently, abdominal surgery is often carried out through laparoscopy, in which surgical tools are manoeuvred through several small incisions in the abdominal wall under general anaesthetics. But in an emerging technique, Natural Orifice Transluminal Endoscopic Surgery (NOTES), the organs are reached through a natural opening in the body, such as the mouth or the vagina.

This type of surgery is not yet a mainstream procedure. “NOTES procedures in patients have been reported worldwide in only about 30 cases”, Schaefer emphasizes. Patients may prefer it because of low postoperative pain discomfort and because of a lack of visible scarring. Schaefer points out that NOTES may also be beneficial from an anaesthetic point of view. The small perforations of the gastric or vaginal wall that are needed to accommodate the surgical tools and the low intra-abdominal pressure that is needed for best visibility may only require spinal or epidural anaesthesia.

Combined with a quick recovery time, low pain levels after surgery and complete absence of visible scars, this may eventually make NOTES the preferred method for abdominal surgeries. “NOTES has the potential to further improve the advantages of laparoscopy”, writes Schaefer, but advises that “these findings need to be corroborated by further randomized controlled clinical trials.”

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Eli Lilly and Company today announced it intends to donate more than
800,000 vials of insulin to the International Diabetes Federation’s Life for
a Child Program, providing free life-saving medicine to as many as 24,000
children who currently have no access to diabetes treatment.

The initial focus of the donations will be to help children with diabetes
in sub-Saharan Africa. This donation will allow the International Diabetes
Federation (IDF) to expand its work meaningfully over the next four years in
at least nine of the poorest countries on the continent.

Lilly’s donation is the largest corporate insulin donation to the Life
for a Child Program and one of Lilly’s largest single contributions of free
insulin in the 85 years since the company introduced the world’s first
mass-produced insulin in 1923.

Lilly made the announcement at this time to commemorate the theme of this
year’s World Diabetes Day (November 14) — diabetes in children and
adolescents.

“Diabetes is emerging as one of the most serious health problems of our
time, and children with diabetes in the developing world are particularly
vulnerable,” said Dr. Carlos Paya, vice president, Lilly Research
Laboratories and leader of Lilly’s Global Diabetes and Endocrine Platform.
“For nearly nine decades, Lilly has been at the forefront of providing
solutions to combat the problems of diabetes around the world, and there is
no more dire need right now than to ensure children with diabetes in the
developing world – particularly sub-Saharan Africa – have access to the
insulin they need to stay alive. We are committed to working with IDF to help
these children survive.”

The Life for a Child Program provides access to care, education and
life-saving medicines and supplies to support children with diabetes in
some of the poorest countries around the world. The program was established
by IDF in partnership with Diabetes Australia-NSW and HOPE worldwide.

The program currently supports 1,100 children and works with diabetes
centers in 18 countries to provide clinical care and diabetes education. It
also aims to raise awareness of the plight of children with diabetes in these
countries and encourages governments to establish appropriate care to
safeguard the future of children with diabetes.

According to IDF, 70,000-75,000 children in low-income and lower-middle
income countries are living with diabetes in desperate circumstances. These
children need life-saving insulin to survive. Even more children are in need
of the monitoring equipment, test strips and education required to manage
their diabetes and avoid the life-threatening complications associated with
the disease.

In many developing countries, particularly in sub-Saharan Africa and some
parts of Asia, life-saving diabetes medication and monitoring equipment is
often unavailable or unaffordable. As a result, many children with diabetes
die soon after diagnosis, or have poor control and quality of life, and
develop the devastating complications of the disease early.

Few governments in sub-Saharan Africa are able to provide free insulin to
children, according to IDF. Families often must purchase the insulin at
premium prices that may equal more than half the family income.

“For any child with diabetes, having access to insulin, a life-saving and
life-sustaining medication, should be a right not a privilege,” said Dr.
Martin Silink, President of the International Diabetes Federation. “The
discovery of insulin 87 years ago was hailed as a miracle. Yet today many
children with diabetes in the developing world still face death because they
cannot access or afford this miracle drug. Solving the complex issues needed
for a sustainable supply chain of insulin and other essential medicines and
having them supported by expert diabetes care will not be easy, but we owe it
to future generations to take this on. IDF has brought together a broad
coalition of global diabetes stake holders to find the means to strengthen
existing healthcare systems for diabetes, lobby for change, and provide the
necessary medication and education to make a real difference. We are already
moving forward. This donation from Lilly is an incredible first step that so
many children with diabetes and their families in the developing world so
desperately need.”

Lilly is already a major supporter of the Life for a Child Program
through contributions from a partnership between the Lilly Foundation and
Rotary International, as well as individual employee contributions that have
helped sustain care for more than 200 children over the last five years.

These new donations of insulin will begin to be distributed in 2009 in
nine African countries: Mali, Uganda, Tanzania, Kenya, Cameroon, Zimbabwe,
Nigeria, Rwanda and the Democratic Republic of Congo. The number of children
is expected to increase with time in each country as more are diagnosed and
survive and more regional centers begin working with the program. The goal is
that by 2012, these new insulin donations should be able to treat up to
24,000 children in the sub-Saharan region.

To further raise awareness of the devastating impact of diabetes and
increase support for the program, Lilly and IDF also produced a documentary
film, called Life for a Child, directed by Academy Award-nominee Edward
Lachman. The film made its world debut in competition at the prestigious
Tribeca Film Festival in New York in April 2008 and its European debut as an
official selection of the Vienna International Film Festival in October. It
will make its world television debut on the Sundance Channel in 2009.

For more information on the Life for a Child Program, please visit
lifeforachild.

About Lilly Diabetes

For more than 85 years, Lilly has been a worldwide leader in pioneering
industry-leading solutions to support people living with and treating
diabetes. Lilly introduced the world’s first commercial insulin in 1923, and
remains at the forefront of medical and delivery device innovation to manage
diabetes. Lilly is also committed to providing solutions beyond therapy
— practical tools, education and support programs to help overcome
barriers to success along the diabetes journey. At Lilly, the journeys of
each person living with or treating diabetes inspire ours. For more
information, visit lifeforachild.

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a growing
portfolio of first-in-class and best-in-class pharmaceutical products by
applying the latest research from its own worldwide laboratories and from
collaborations with eminent scientific organizations. Headquartered in
Indianapolis, Ind., Lilly provides answers — through medicines and
information — for some of the world’s most urgent medical needs. Information
about Lilly is available at lilly.

Eli Lilly and Company Continue reading →

Vigabatrin, a medication proposed as a potential treatment for drug addiction by scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory, also leads to rapid weight loss and reduced food intake according to a new animal study from the same research group. The study was published online August 20, 2008, by the journal Synapse. Vigabatrin is currently undergoing U.S. Food and Drug Administration (FDA)-approved Phase II clinical trials against cocaine and methamphetamine addiction across the U.S.

In the current study, animals genetically bred to be obese experienced a loss of up to 19 percent of their total weight while non-obese animals lost 12 to 20 percent following short-term vigabatrin administration.

“Our results appear to demonstrate that vigabatrin induced satiety in these animals,” said Amy DeMarco, who led the study, working in the laboratory of Brookhaven Lab senior scientist Stephen Dewey. Dewey first identified vigabatrin as a potential addiction treatment and has conducted more than 20 years of preclinical research with this promising medication.

Earlier studies at Brookhaven Lab found a strong connection between obesity and addiction, including similar changes in the brains of the obese and those addicted to drugs like cocaine. Based on these connections, Dewey hypothesized that vigabatrin would quench food cravings in the lab rats.

“Given the growing obesity epidemic, we felt that examining vigabatrin’s therapeutic efficacy for obesity was particularly relevant,” Dewey said. A total of 50 adolescent and adult animals, both genetically bred “fat” and normal-weight animals, were assigned to either a control group or groups that received vigabatrin at various dose levels and were monitored for up to 40 days. The controls received daily salt water (saline) injections, while those in the study groups received up to 300 milligrams (mg) of vigabatrin a day. All animals received injections for two 7-13-day periods, with breaks in between.

At the end of the 40-day period, all animals receiving vigabatrin weighed significantly less than the controls. The obese animals receiving the 300mg dose weighed far less and consumed less food than the 150 and 75mg groups. The obese animals receiving vigabatrin lost an average of 19 percent of their initial weight, while non-obese animals lost between 12 and 20 percent of their weight.

“The fact that these results occurred in genetically obese animals offers hope that this drug could potentially treat severe obesity,” said Dewey. “This would appear to be true even if the obesity results from binge eating, as this disorder is characterized by eating patterns that are similar to drug-taking patterns in those with cocaine dependency.”

Dewey and Jonathan Brodie, a professor of psychiatry at New York University School of Medicine, have conducted extensive studies on animals at Brookhaven Lab showing that vigabatrin attenuates or blocks neurological and behavioral changes associated with drug addiction. Vigabatrin has been tested in humans in two small open-label studies, as well as in a 103-patient double-blinded, placebo-controlled trial. Vigabatrin is now being commercialized by Catalyst Pharmaceutical Partners, which is currently conducting two FDA-approved Phase II trials. For more on Brookhaven National Laboratory’s addiction treatment research, see bnl/CTN/GVG. For more information about Catalyst Pharmaceutical Partners, see catalystpharma/.

This research was funded by the National Institute on Drug Abuse at the National Institutes of Health and by the Office of Biological and Environmental Research within DOE’s Office of Science. Brookhaven Lab has a world-renowned research program aimed at understanding the neurological mechanisms and consequences of drug addiction and other addictive behaviors. This program is fueled, in part, by DOE’s long-standing support of brain-imaging technologies developed as a direct outgrowth of their commitment to basic physics and nuclear chemistry research.

All research involving laboratory animals at Brookhaven National Laboratory is conducted under the jurisdiction of the Lab’s Institutional Animal Care and Use Committee in compliance with the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals, the U.S. Department of Agriculture’s Animal Welfare Act, and the National Academy of Sciences’ Guide for the Care and Use of Laboratory Animals. This research has enhanced understanding of a wide array of human medical conditions including cancer, drug addiction, Alzheimer’s and Parkinson’s diseases, and normal aging and has led to the development of several promising treatment strategies.

RELATED INFORMATION

Links to the studies described below appear on the web version of this news release at: bnl/bnlweb/pubaf/pr/PR_display.asp?prID=811)

Stephen Dewey and colleagues have conducted more than 20 years of research on vigabatrin as a potential addiction treatment.

Pre-clinical (animal) studies have:
demonstrated that vigabatrin blocks dopamine increases triggered by environmental cues related to drug use

demonstrated that vigabatrin blocks the process in the brain that causes cocaine’s “high”

demonstrated that vigabatrin does the same for nicotine

shown that vigabatrin may block the addictive effects of toluene, a commonly used inhalant

Clinical milestones include:
the first small clinical trial of vigabatrin showed prolonged abstinence and elimination of drug craving in long-term cocaine addicts

the second small clinical trial of vigabatrin showed prolonged abstinence and no visual problems in cocaine and methamphetamine abusers

vigabatrin’s first Phase II, double-blind placebo-controlled trial shows positive results in treating cocaine abuse an FDA-sanctioned, Phase II multicenter study of vigabatrin starts

The neurobiology of eating disorders and obesity and their treatment is another major focus of research at Brookhaven Lab. Earlier studies at the Lab have:
identified brain circuits that may cause the obese to overeat

shown that levels of dopamine receptors, which receive chemical messages of well being and reward in the brain, are decreased in the brains of obese individuals

demonstrated that parts of the brain responsible for sensation in the tongue, mouth, and lips are more active in the obese

revealed that the mere sight and smell of favorite foods spikes levels of dopamine in the brains of food-deprived people – just as it spikes this pleasure chemical in the brains of those with drug addictions in response to their drug of choice

One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE’s Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.

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CEL-SCI Corporation (NYSE AMEX: CVM) announced it has received governmental approval from the Ministry of Health Care and Social Development of the Russian Federation to begin enrollment of subjects for a Phase III clinical trial of Multikine® in Russia. Russia is one of nine countries to participate in this global Phase III trial. The Phase III trial will be run at about 48 clinical centers. Three are expected to be located in Russia. The Phase III trial was started late last month in the United States. It is expected that all 48 clinical centers will be enrolling patients within a few months. Multikine is the Company’s flagship immunotherapy developed as a first-line standard of care in treating head and neck cancer.

CEL-SCI’s Phase III clinical trial is an open-label, randomized, controlled, multi-center study designed to determine if Multikine administered prior to current standard of care (Surgery plus Radiotherapy or Surgery plus Concurrent Chemo radiotherapy) in previously untreated subjects with Advanced Primary Squamous Cell Carcinoma of the Oral Cavity/Soft Palate (Head and Neck cancer) will result in an increased overall rate of survival versus the subjects treated with standard of care only. CEL-SCI’s 880 patient trial is expected to be the largest clinical study of head and neck cancer ever conducted. It will also be the first trial in which immunotherapy will be administered before any other traditional means of care are attempted. This is significant because conventional therapy weakens the immune system, and likely compromises the benefits of immunotherapy.

Phase II clinical trials of Multikine demonstrated the product was safe and well-tolerated and eliminated tumors in 12% of the subjects less than a month into treatment. The Multikine treatment regimen was also shown to kill, on average, about half of the cancer cells in the subjects’ tumors before the start of standard therapy. Follow-up studies of subjects enrolled in Phase II trials showed a 33% improvement in the survival rate of those treated with Multikine at a median of three and a half years following surgery. The U.S. Food and Drug Administration granted orphan drug status to Multikine in the neoadjuvant therapy of patients with squamous cell carcinoma of the head and neck.

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