Month: September 2013
Researchers have discovered a class of FDA-approved antidepressants that may prove effective in treating patients with small-cell lung cancer – one of the deadliest forms of the disease.
Small-cell lung cancer (SLC) comprises 15 percent of all lung cancers and has a particularly grim prognosis rate.
“SLC is a bad cancer to have,” Dr. Atul Butte, the study’s lead author of the Stanford University School of Medicine. “The five-year survival is only 5 to 6 percent, and most people present with extensive stage cancer.”
The disease is a form of cancer known as neuroendocrine cancer – the same type of cancer that Steve Jobs was diagnosed with – for which few targeted treatments are available.
Rather than developing new drugs to treat diseases like SLC, Butte and his colleagues have long been interested in the concept of identifying already FDA-approved drugs that might be repurposed to treat new disorders. With this purpose in mind, Butte’s laboratory developed a computer algorithm able to identify drugs that target genes associated with certain diseases – and match them with one another.
“Basically, a report in the past called for drugs,” Butte said.
Using this computerized discovery pipeline, the researchers began to explore whether any existing drugs might prove effective at killing SLC cells.
“What we started with was looking at experiments where people submitted normal tissue and SLC tissue from the same patients,” Butte said. “We (identify) the gene that is most different in the cancerous cells and then find a drug to reverse that effect.”
Eventually, researchers hit upon a drug called imipramine, which is part of a class of FDA-approved drugs known as tricyclic antidepressants. When researchers exposed SLC-infected tissues to imipramine, the cancerous cells appeared to die off. Researchers tested the drug with success in both a lab setting and using mice genetically engineered to develop small-cell lung cancer.
While tricyclic antidepressants are still on the market, they’ve been overshadowed by the popularity of newer classes of antidepressants, including selective-serotonin reuptake inhibitors (SSRIs), like Prozac, which have been proven to have fewer side effects.
“But not so long ago (tricyclic antidepressants) were commonly used,” Butte said. “They do have side effects, the biggest is on the heart, like arrhythmia… that being said these drugs are still in the pharmacy and you can get them.”
Because these drugs are already FDA-approved, researchers were able to start recruiting patients for phase 2 clinical trials within 15 to 20 months of their discovery.
“Usually it takes $4 billion and 10 plus years to get a brand new drug to market,” Butte said. “This could be a shortcut – finding a drug that works and borrowing it for other disease. We don’t know yet if the trial will work or not but its amazing it will get to trial so quickly.”
However, Butte warns that just because the drug is already on the market, doesn’t mean that patients should attempt to self-medicate.
“We would strongly encourage them to join a trial and get this kind of medication in a research setting, making sure they’re following safety guidelines for this category,” Butte said.
When a particular circuit in the brain is stimulated, it causes mice to voraciously gorge on food even though they are well fed, and deactivating this circuit keeps starving mice from eating, a new study shows.
The findings suggest that a breakdown within this neural network could contribute to unhealthy eating behaviors, the researchers said, although more work is needed to see whether the findings are also true of people.
The circuit lies in a brain area called the “bed nucleus of the stria terminalis” (BNST), and affects eating by inhibiting activity in another region, called the lateral hypothalamus, which is known to control eating, according to the study, published Sept. 26 in the journal Science.
“Normally, there’s a population of neurons in the lateral hypothalamus that’s putting the brakes on eating,” said study researcher Garret Stuber, a neuroscientist at the University of North Carolina at Chapel Hill. “But when you shut those cells down by stimulating this pathway, that releases the brake, and the animal starts to eat.”
The lateral hypothalamus has been known for more than 50 years to be an important part of the brain for controlling eating. Scientists had learned that putting stimulating electrodes in the lateral hypothalamus of animals would influence their eating behavior, but exactly how it works has been a mystery.
“Nobody had a good mechanistic explanation for what’s actually being stimulated or activated within this brain structure,” Stuber said.
In the new study, the researchers focused on examining how the BNST influences activity in the lateral hypothalamus.
To manipulate the BNST neurons, the researchers used a technique called optogenetics that allowed them to activate specific neurons using light. They found that, upon activation, BNST neurons suppressed activity in the lateral hypothalamus, and caused the well-fed mice to immediately start eating.
“When we stimulate the pathway, the animals eat a third to 50 percent of the calories they eat in a normal day, in about 20 minutes,” Stuber said. For a person, that would probably be the equivalent of eating lunch and dinner in one sitting, he said.
What’s more, the researchers gave the animals a choice in some of the experiments between regular food and a tasty food with a high fat content, analogous to junk food. They found that when they activated the circuit, the animals showed a strong preference for the junk food.
Conversely, deactivating the circuit caused the animals to immediately stop eating, even if their stomachs were empty.
The BNST is thought to be a hub that integrates emotionally relevant information coming from several parts of the brain. Although the experiments didn’t aim to study the link between emotional states and feeding behavior, the findings may explain how emotions can influence eating, Stuber said.
“BNST is really important for affective behavior state in response to emotionally relevant stimuli, and the results show the output of those cells can actually directly modulate feeding behavior,” he said.
Identifying a neural circuit that controls feeding, and understanding how the cells in this circuit work, could lead to future treatments for such conditions as obesity, the researchers said.
“Now that we know this is a critical circuit for feeding, we can start looking at this in humans,” Stuber said.
In an episode of the television series “Homeland,” a terrorist organization assassinates the vice president of the United States by wirelessly hacking into his pacemaker. Although the scenario was fictional, the underlying premise is not.
Life-saving medical devices abound in today’s world, and many of these devices are connected wirelessly to hospital networks, making them vulnerable to cyberattacks. For example, a malicious person could hack into a pacemaker, causing the device to apply lethal electrical stimulation, or an insulin pump, causing it to deliver a deadly dose of the hormone.
“Just like any other piece of Internet technology, medical devices are susceptible to the same cyberthreats you hear about all the time on the news,” said Russel Jones, a partner at the consulting firm Deloitte, which released a report on Sept. 23 on the subject of cybersecurity in medical devices.
As more and more medical devices go online, device manufacturers and health care organizations will need to address security issues to keep patients and their health information safe.
So far, there have been no known incidents of a hacked medical device injuring or killing a person, but researchers have demonstrated that these events are possible “with the right level of skill and understanding,” Jones said.
In the Deloitte study, consultants interviewed representatives from nine health care organizations, in areas spanning from information technology to clinical engineering. The participants answered questions about the regulation, risk management and security of networked medical devices.
The majority of organizations surveyed felt their organizations had strategies and frameworks for managing cybersecurity risks. However, there were differences in the degree of preparedness and approaches for handling cyberthreats.
One way to protect information sent to or from a medical device is to encrypt it. The problem is, encryption takes up valuable processing time on the device. The challenge, Jones said, is to develop encryption that addresses cyberrisk without impacting the functionality of the device.
In June, the U.S. Food and Drug Administration (FDA) released draft guidance for cybersecurity concerns. The FDA’s previous guidance from 2005 was pretty vague, but the new draft lays out specific concerns that must be addressed when applying for FDA approval for new devices.
Ensuring cybersecurity in medical devices will require collaboration, Jones said. “This is going to be a problem that’s jointly solved by health care systems, providers, device manufacturers and the FDA,” he said.
Two top reproductive health organizations have taken on the controversial subject of chemicals in the environment, saying the federal government isn’t doing enough to keep people safe.
They say chemicals might cause a range of problems, from birth defects to diabetes, but also say there isn’t enough research to show which ones are the most dangerous.
But other experts say the joint statement from the American College of Obstetricians and Gynecologists (ACOG) and the American Society of Reproductive Medicine (ASRM) is too broad, and that it will probably needlessly scare pregnant women without offering much useful new advice.
“The real goal is to raise awareness, increase the education of health care professionals — physicians, nurses, office staff — and patients who are either pregnant or are thinking of getting pregnant with regard to some of the environmental threats,” said Dr. Jeanne Conry, president of ACOG.
“There is a backdrop of disease processes that have increased in the past 30-40 years. In that backdrop we have seen an increase in the release of chemicals into the environment.”
The statement, published in the journals Fertility and Sterility, calls for doctors to help patients reduce their exposure to chemicals. “Reducing exposure to toxic environmental agents is a critical area of intervention for obstetricians, gynecologists, and other reproductive health care professionals,” it reads.
The problem, says Dr. Janet DiPietro, associate dean of research at Johns Hopkins University, is that what they can do isn’t always very clear. “What is your average OB going to say?” asked DiPietro, a reproductive health expert who was not involved in writing the statement.
It’s true that pregnant women have chemicals circulating in their bodies, say DiPietro and other experts. Studies have shown that chemicals such as DDT are in virtually every human being’s body.
“There is very little that a provider can tell women to do or that women can avoid, from a practical perspective,” DiPietro said in a telephone interview. “We have relatively little data on either the fetal effects or long-term developmental effects,” she added.
“So you tell a woman, ‘OK you have DDT in your system. It may have come from your mother. It may have come from your environment when you were a kid.’ But what are you going to do about it?”
Some of the chemicals mentioned in the ACOG/ASRM statement have been clearly shown to be harmful — mercury and lead, for instance. But the evidence about some of the others, such as bisphenol A (BPA) and a large group of chemicals called phthalates, is less clear. The Food and Drug Administration says BPA, for instance, is safe, even if it does get into food.
The FDA stopped allowing the use of BPA in baby bottles and sippy cups, but only after manufacturers of those products stopped using it voluntarily.
Tracey Woodruff, director of the Program on Reproductive Health and the Environment at the University of California, San Francisco, — who played a role in developing the statement — says agencies like the FDA should do more.
“The problem with the regulatory agencies is they are not keeping up with the science,” Woodruff said in a telephone interview.
But she agreed it could be difficult to tell people to avoid chemicals without knowing whether the alternatives are any safer. “This issue about alternatives are a real challenge. Maybe you choose another plastic water bottle. Maybe it is BPA-free but we don’t know what’s in another plastic water bottle,” Woodruff said.
But she said government agencies should ask these questions. “You know why we don’t know? It is because the government doesn’t have the power to require the testing.”
Scientists working to test the safety of chemicals say it is very hard to determine if a specific chemical is harmful because people have so many circulating in their bodies. Is it the chemical that is harmful, or something else that causes it to build up in the body? And other factors, such as obesity and a lack of exercise, may play a bigger role in reducing fertility in both men and women, studies suggest.
Dr. Linda Giudice, president of ASRM, says there is good evidence in many areas. “I think a really good example is cigarette smoking,” she said. Women who smoke are more likely to have dangerously small babies, she said. “Women who smoke actually have almost two times the need for services, medical therapy, for achieving pregnancy,” Giudice added.
And she defended the need to talk to patients about chemicals whose threats are not yet clearly established. “If it is biologically plausible and we have a way to minimize exposures, I think that is an important contribution,” Giudice said. “We don’t want everyone being afraid to go outside or to use their personal care products or to walk outside and breathe the air. But it is important that if it is a very polluted day that one may choose to stay indoors.”
“I think they make it sound like the knowledge base is clearer than it is,” counters DiPietro. “I tell pregnant women you should be issued a pair of earmuffs to wear. We know we are all living in a chemical brew and what about it?”
With anesthetics properly given, very few patients wake up during surgery. However, new findings point to the possibility of a state of mind in which a patient is neither fully conscious nor unconscious, experts say.
This possible third state of consciousness may be a state in which patients can respond to a command, but are not disturbed by pain or the surgery, according to Dr. Jaideep Pandit, anesthetist at St John’s College in England, who discussed the idea Thursday at The Annual Congress of the Association of Anaesthetists of Great Britain and Ireland.
Pandit dubbed this state dysanaesthesia, and said the evidence that it exists comes partly from a recent study, in which 34 surgical patients were anesthetized, and had their whole body paralyzed except for their forearm, allowing them to move their fingers in response to commands or to signify if they are awake or in pain during surgery.
One-third of patients in the study moved their finger if they were asked to, even though they were under what seemed to be adequate anesthesia, according to the study led by Dr. Ian F. Russell of Hull Royal Infirmary in England and published Sept. 12 in the journal Anaesthesia.
“What’s more remarkable is that they only move their fingers if they are asked. None of the patients spontaneously responded to the surgery. They are presumably not in pain,” said Pandit, who wrote an editorial about the study.
Normally, while patients are under anesthesia, doctors continuously monitor them, and administer anesthetic drugs as needed. The goal is to ensure the patient has received adequate medication to remain deeply unconscious during surgery. However, it is debated how reliable the technologies used during surgery to “measure” unconsciousness are.
“We don’t have a model for consciousness,” Pandit said. “It is very difficult to design a monitor, to monitor something you don’t have a model for.
The study of 34 patients was aimed at investigating whether patients are fully unconscious when the monitoring technology commonly used in the operating rooms indicates so. The researchers kept patients’ arms separated from rest of the body, which was receiving routine paralyzing drugs, by blocking the blood supply. Patients were able to move their arm if they were still conscious.
In the patients who responded to the doctor’s command by moving their hand, the doctors took it as a sign of consciousness, and increased the anesthetic dose.
However, Pandit argues these patients were not “conscious.” The fact that patients only responded to command, and didn’t move spontaneously, shows their state of mind is different from normal consciousness, he said.
The idea of a third state of consciousness may explain the discrepancies in the reported prevalence of awareness during surgery, Pandit said. Previous surveys have shown that when patients are asked if they recalled being aware during surgery, about 1 in 500 will say they did. In contrast, a recent national survey in the United Kingdom, in which patients were not directly asked about awareness during surgery, 1 in 15,000 patients spontaneously reported they were aware during their surgery. Only 1 in 45,000 reported pain or distress during their surgery.
Together, these statistics suggest there’s a state in which patients are aware but not reporting it, perhaps because it is an acceptable and neutral experience for them, Pandit said. They may be aware of their surroundings to some extent, but not concerned by this knowledge, especially because they are not in pain.
Pandit’s hypothesis may serve as basis for developing anesthesia monitors in the future, he said. Although the state of dysanaesthesia seems harmless, it could be a precursor to unpleasant awareness during surgery that doctors, and patients, wish to avoid.
“It’s a hypothesis for future research, it’s something that we can explore further and design experiment to see if it really exist,” he said.
The risk of developing cloudy lenses in the eyes may be linked to the use of cholesterol-lowering drugs known as statins, according to a new study.
While the researchers can’t prove the drugs caused the eye condition, they found that people who took statins – such as Zocor and Lipitor – were about 27 percent more likely to develop cataracts, compared to people who didn’t take the medication.
“The results were consistent that there was a higher risk of being diagnosed with cataracts among statin users,” Dr. Ishak Mansi, the study’s senior author from UT Southwestern Medical Center and the Dallas VA Medical Center in Texas, said.
Statins are popular drugs that block a substance the body needs to make cholesterol, which can get trapped in arteries and ultimately lead to heart attacks and strokes.
About one-quarter of U.S. adults aged 45 and older take statins. The drugs are especially recommended for people with diabetes or a history of cardiovascular problems.
Researchers have looked at the link between statins and cataracts before with mixed results. While some studies found that taking statins lowered the risk of developing cataracts, other studies found the drugs increased the risk.
For the new research, Mansi and his colleagues used data collected from the medical records of people between the ages of 30 and 85 years old who were enrolled in one healthcare system in San Antonio, Texas, and received care between 2003 and 2005.
In one analysis, they compared about 7,000 people who were on statins for at least 90 days to about 7,000 people who were not on statins but were similar in about 40 other characteristics, including other health conditions, medications and healthcare use.
About 36 percent of statin users were diagnosed with cataracts, compared to about 34 percent of people not taking statins.
In a second analysis, the researchers looked at people with no other known health conditions. It included 6,113 statin users and 27,400 people who did not take statins.
After adjusting the results for the participants’ age, sex, weight, medications, healthcare use, other vision conditions and cigarette, alcohol and drug use, the researchers found about 34 percent of statin users were diagnosed with cataracts, compared to about 10 percent of people not taking statins.
What’s more, the researchers found that the risk of developing cataracts increased with the length of time a person took the medication.
While Mansi and his colleagues can’t say how statins may affect the formation of cataracts, they write in JAMA Ophthalmology that there are a few possible explanations.
One is that the body needs high levels of cholesterol to maintain a clear lens and statins may interfere with the cells that control that process.
Dr. Jack Cioffi, head of ophthalmology at Columbia University Medical Center in New York, said the study is very well done, but has some limitations, including that the researchers used billing data rather than medical records, so they can’t say how severe the cataracts were.
“I don’t think we should overstate the significance of this. It goes back to if there is a good reason for you to be on that statin, it outweighs the risk of a mild increase in risk of cataract,” Cioffi, who was not involved in the new study, said.
He added that the treatments for cataracts have evolved over time. The National Institutes of Health says the procedures to remove cataracts are some of the most common and safest surgeries performed in the U.S.
“For patients themselves, my advice is to discuss what your benefit and risk ratio is for you with your doctor,” said Mansi, who added that he hopes the results will also encourage people to improve their cholesterol levels through lifestyle changes.
“This should motivate patients to do their part. Quit smoking, eat healthy and be active so doctors don’t have to give you a tablet that may have some side effects,” he said.