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    <recommendedItem id="20100101_19_341"
                     title="Doctor&apos;s Orders: Brain&apos;s Wiring Makes Change Hard"
                     score="0.008"
                     href="http://www.medpagetoday.com/Psychiatry/Addictions/tb/18207?impressionId=1265800177475"
                     
      &lt;p&gt;Doctor&apos;s Orders&lt;em&gt; is a feature in the collaboration between &lt;/em&gt;MedPage Today &lt;em&gt;and&lt;/em&gt; ABC News&lt;em&gt;. In this monthly segment we explore medical issues of interest to physicians and their patients alike. This month, we look at addiction and addictive behaviors, and what neuroimaging studies have revealed about why it&apos;s so hard to break bad habits. &lt;/em&gt;&lt;/p&gt;&lt;hr&gt;

&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;

&lt;p&gt;By the end of January, many New Year&apos;s resolutions have been tossed out with the leftover holiday cookies. That&apos;s because change is hard  --  and neuroscientists are learning why.&lt;br&gt;
&lt;br&gt;Advances in neuroimaging have enabled researchers to peer inside the brains of addicts and patients with addictive behaviors. They can see in real-time what gets patients hooked: how the brain&apos;s reward system  --  based largely on the neurotransmitter dopamine  --  thirsts for more, while inhibitory control centers experience a system failure.&lt;br&gt;
&lt;br&gt;The pattern is similar across all kinds of behaviors  --  from cocaine and tobacco addiction to overeating. That&apos;s why changing your mind may be the first step toward breaking a habit, but altering the brain&apos;s neural machinery is the real challenge.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Hijacked Pathways&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Drug-taking and other addictive behaviors &quot;hijack&quot; the brain&apos;s reward system, says Petros Levounis, MD, director of the Addiction Institute of New York at St. Luke&apos;s and Roosevelt Hospitals in Manhattan.&lt;/p&gt;
&lt;p&gt;In normal patients, dopamine plays a major role in motivation and reward, surging before and during a pleasurable activity  --  say, eating or sex  --  to make patients want to repeat a behavior that&apos;s crucial to the survival of the species.&lt;/p&gt;
&lt;p&gt;Dopaminergic pathways connect the limbic system, responsible for emotion, with the hippocampus, etching rewarding behaviors into the brain by creating strong, salient memories.&lt;/p&gt;
&lt;p&gt;The problem arises when the memory and the craving to recapture it takes over a person&apos;s life.&lt;/p&gt;
&lt;p&gt;&quot;Imagine what a strong hold these hijacked reward pathways take on our brains and our whole existence when they&apos;re so closely connected, geographically and anatomically speaking, with our memories and our emotions,&quot; Levounis says.&lt;/p&gt;
&lt;p&gt;As the dopamine surge repeats and repeats, it gains speed, but the brakes begin to fail: Normal function in the brain&apos;s frontal lobes, responsible for inhibitory control and executive functioning (read: willpower), tends to decrease in addicts.&lt;/p&gt;
&lt;p&gt;&quot;Ultimately,&quot; Levounis says, &quot;the war on drugs is a war between the hijacked reward pathways that push the person to want to use, and the frontal lobes, which try to keep the beast at bay. That is the essence of addiction.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Similar Patterns&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;These neural pathways have been well studied in the brains of hardcore addicts. Now, researchers say they see similar pathways involved in other bad behaviors.&lt;/p&gt;
&lt;p&gt;Gene-Jack Wang, MD, of Brookhaven National Laboratory on New York&apos;s Long Island, has conducted several brain imaging studies of obese patients using PET-CT scans.&lt;/p&gt;
&lt;p&gt;The scans have revealed similarities in brain activity  --  or a lack thereof  --  between patients addicted to cocaine or alcohol, and those &quot;addicted&quot; to eating. Normally, the PET scan lights up when a contrast of radioactive glucose is metabolized, revealing an area of red activity in the center of the brain.&lt;/p&gt;
&lt;p&gt;But in both drug-addicted and obese patients, the scans show very little red activity, because there aren&apos;t enough receptors to which the radioactive glucose can bind. Wang says the decreased availability of dopamine receptors is the brain&apos;s way of coping with a constant dopamine overload.&lt;/p&gt;
&lt;p&gt;&quot;If a person constantly has an excess of dopamine, the brain will down-regulate,&quot; Wang says, explaining the principle commonly referred to as tolerance. &quot;Once the system is down-regulated, we have to do more in order to get the same amount of feeling in our normal state.&quot;&lt;/p&gt;
&lt;p&gt;Thus, obese patients &quot;will want to eat more in order to compensate for their down-regulated system.&quot;&lt;/p&gt;
&lt;p&gt;In other experiments, Wang and his colleagues have also found that a higher body mass index (BMI) correlated with lower prefrontal cortex function  --  the area associated with inhibitory control.&lt;/p&gt;
&lt;p&gt;&quot;If they&apos;re obese,&quot; Wang said, &quot;they have a problem controlling their eating behaviors.&quot;&lt;/p&gt;
&lt;p&gt;Those studies also revealed that a higher BMI was linked to a decrease in memory and executive functioning.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Out of Control&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Ed Susman was 293 pounds when he decided to join a clinical trial for an investigational weight-loss drug and chronicle his year-long experience for &lt;em&gt;MedPage Today&lt;/em&gt;. (See &lt;a href=&quot;http://www.medpagetoday.com/PrimaryCare/Diabetes/8125&quot; mce_href=&quot;http://www.medpagetoday.com/PrimaryCare/Diabetes/8125&quot; target=&quot;_blank&quot;&gt;Journalist Participant to Present Insider View of Weight-Loss Trial&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Eating, to him, was a &quot;compulsion&quot;  --  as was biting his nails, a habit he picked up at age 4.&lt;/p&gt;
&lt;p&gt;Over the course of the trial, not only did Susman lose 52 pounds, he also stopped his nail-biting.&lt;/p&gt;
&lt;p&gt;He doesn&apos;t yet know if he was in the drug arm of the trial, but he strongly suspects he wasn&apos;t experiencing a placebo effect.&lt;/p&gt;
&lt;p&gt;&quot;I believe I was on the drug because it controlled a compulsion that I had had for 50 years,&quot; Susman says of the nail-biting. &quot;This stopped it cold.&quot;&lt;/p&gt;
&lt;p&gt;Unfortunately, he says, the same didn&apos;t happen with his eating habits, but he&apos;s gained back only 10 of those 52 pounds in the year since his participation in the trial ended.&lt;/p&gt;
&lt;p&gt;The still-investigational drug is lorcaserin  --  a combination of benzazepine and hydrochloride, two neurological agents. Susman says it is &quot;supposed to improve your willpower, your ability to overcome compulsions.&quot;&lt;/p&gt;
&lt;p&gt;Lorcaserin is a selective 5-HT&lt;sub&gt;2C&lt;/sub&gt; receptor agonist, working through the serotonin system, which regulates appetite, mood, and motor behavior.&lt;/p&gt;
&lt;p&gt;Two other investigational obesity drugs target the dopamine reward system  --  Contrave, which is a combination of bupropion and naltrexone, and Qnexa, which combines phentermine and topiramate.&lt;/p&gt;
&lt;p&gt;&quot;Some medications that have used similar dopamine modulation, until now, have failed,&quot; Wang said. &quot;These two companies are using the command of the modulation of the dopamine system with other neurological systems, such as the opiate or norepinephrine system. According to the trials, they&apos;ve been very effective.&quot;&lt;/p&gt;
&lt;p&gt;Wang called the new medications &quot;a bright light for the treatment of obesity.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Kicking the Habit&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Basically, the idea of medications that act on the dopamine system is &quot;to cool down those reward pathways,&quot; Levounis says. There are two strategies for doing so: an agonist strategy, or an antagonist strategy.&lt;/p&gt;
&lt;p&gt;The agonist strategy is &quot;feeding the beast, providing activity in the cell so that the cravings go down,&quot; Levounis said. Classic examples are nicotine patches, or methadone for opioid dependence.&lt;/p&gt;
&lt;p&gt;On the other hand, the antagonist strategy is to block the receptors. Naltrexone, for example, will block opioid receptors so that the drug addict won&apos;t feel anything if he or she attempts to get high.&lt;/p&gt;
&lt;p&gt;&quot;After a while, you say, &apos;This is not worth my time, my money, my trouble,&apos; so you stop using,&quot; Levounis explains.&lt;/p&gt;
&lt;p&gt;These have been the two main strategies in addiction pharmacotherapy, but there&apos;s now a &quot;third avenue&quot;  --  the partial agonist approach.&lt;/p&gt;
&lt;p&gt;The partial agonist is one molecule that blocks most receptors while still providing just a little bit of an &quot;oomph&quot; to calm cravings. That&apos;s how varenicline (Chantix) helps smokers quit, and how buprenorphine gets junkies off heroin or other opioids.&lt;/p&gt;
&lt;p&gt;But what about inhibitory control? What if medications could ramp up will power?&lt;/p&gt;
&lt;p&gt;&quot;It&apos;s an area of active research,&quot; Levounis says. &quot;There are some medications proposed, but nothing to write home about.&quot;&lt;/p&gt;
&lt;p&gt;He said treatment is typically twofold. For addicts, psychiatrists will try to &quot;cool down&quot; the reward pathways, often with medication. Then, they target the diminished frontal lobes.&lt;/p&gt;
&lt;p&gt;&quot;We try to beef up the frontal lobes as much as we can, and we do that with psychotherapy,&quot; Levounis said.&lt;/p&gt;
&lt;p&gt;Researchers agree that psychotherapy is key to regaining self-control, and it&apos;s the predominant treatment used in patients with addictive behaviors.&lt;/p&gt;
&lt;p&gt;Mark Smaller, PhD, a psychoanalyst in private practice in Chicago, said psychotherapy often reveals an underlying cause for an addiction or compulsive behavior. Usually, it&apos;s anxiety or depression.&lt;/p&gt;
&lt;p&gt;Acknowledging those problems may help change behaviors. Once they&apos;re realized, a patient can start working against them, with the help of the brain&apos;s own neuroplasticity. Essentially, neurons can disconnect and reconnect, or loosen their connections and tighten them, which often manifests in noticeable change.&lt;/p&gt;
&lt;p&gt;&quot;[Psychological] insights can actually begin to change brain chemistry and diffuse compulsions,&quot; he said. &quot;If you address those issues, you can have a positive impact on your life that can change the chemistry of your brain.&quot;&lt;/p&gt;
&lt;p&gt;Smaller said it &quot;creates a new psychological  --  if not neurological  --  structure that can help regulate behavior.&quot;&lt;/p&gt;
&lt;p&gt;Although research on neuroplasticity is relatively young, the concept of &quot;rewiring&quot; the brain is not new.&lt;/p&gt;
&lt;p&gt;In fact, too often, the electrician metaphor has been employed as an excuse for indulging, an explanation for a New Year&apos;s resolution deferred: &quot;I can&apos;t stop eating chocolate, I&apos;m just not wired that way.&quot;&lt;/p&gt;

&lt;hr&gt;
&lt;p&gt;&lt;img src=&quot;http://www.medpagetoday.com/upload/2009/10/30/16717.jpg&quot; mce_src=&quot;http://www.medpagetoday.com/upload/2009/10/30/16717.jpg&quot; alt=&quot;&quot;&gt;&lt;em&gt; is a collaboration between &lt;/em&gt;MedPage Today &lt;em&gt;and&lt;/em&gt; ABC News&lt;em&gt;.&lt;/p&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_304"
                     title="&apos;Virtual&apos; Colon Scans Effective in Seniors (CME/CE)"
                     score="0.003"
                     href="http://www.medpagetoday.com/HematologyOncology/ColonCancer/tb/18164?impressionId=1265800177475"
                     
      Patients 65 and older are as suitable as younger individuals for CT colonography, said researchers conducting a large retrospective study.&lt;br&gt;
&lt;br&gt;Advanced neoplasias were detected with CT colonography  --  often called &quot;virtual colonoscopy&quot;  --  in older patients at more than double the rate in the general screening population, reported David H. Kim, MD, of the University of Wisconsin in Madison, Wis., and colleagues in the February issue of &lt;em&gt;Radiology&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;They found that 7.6% of older patients had advanced neoplasias, compared with 3.2% of all patients screened in the university&apos;s clinic (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;On the basis of this and other findings in 577 individuals 65 and older versus the entire group of 3,120 patients undergoing the procedure, Kim and colleagues concluded that &quot;CT colonography performance is maintained in an older cohort.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Overall, the observations from this clinical experience confirm that CT colonography may be a valuable screening modality in the older population,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;On the other hand, the study did not address several objections raised by the Centers for Medicare and Medicaid Services (CMS) in its decision last year to deny Medicare coverage for the procedure. (See &lt;a href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/Medicare/14186&quot; mce_href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/Medicare/14186&quot; target=&quot;_blank&quot;&gt;Medicare Finalizes Denial of Virtual Colonoscopy Coverage&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;CMS had pointed to relatively low sensitivity of CT colonography compared with optical colonoscopy in prospective trials, especially for small lesions.&lt;/p&gt;
&lt;p&gt;The agency also determined that CT colonography increased the costs of positive findings, since abnormalities in the CT scans must be confirmed with optical colonoscopy. In addition, CMS said there was no evidence to support claims that the less invasive imaging procedure would be more acceptable to patients and therefore would raise screening rates.&lt;/p&gt;
&lt;p&gt;The data analyzed by Kim and colleagues did not allow for calculations of false-negative rates or predictive values of positive or negative findings. Nor did the researchers report cost information.&lt;/p&gt;
&lt;p&gt;Mean age of their older cohort was 69.2 (SD 3.8). The oldest was 79.&lt;/p&gt;
&lt;p&gt;The researchers reported that 15.3% of the older patients were referred for optical colonoscopy on the basis of the CT results, compared with 7.9% of the overall screening group.&lt;/p&gt;
&lt;p&gt;Less than 4% of positive findings were determined to be false with the optical procedure (3.6% for polyps 6 to 10 mm in diameter, 2.1% for larger lesions).&lt;/p&gt;
&lt;p&gt;Of the 59 advanced neoplasias identified in the older patients, all but three were at least 10 mm in size.&lt;/p&gt;
&lt;p&gt;The scans also suggested abnormalities outside the colon in 89 (15.4%) patients. Of these, 45 received a full workup, which revealed substantial and previously unsuspected diagnoses in 21 cases  -- 18 were vascular aneurysms. The other three included one lung tumor, a femoral hernia, and a malrotation.&lt;/p&gt;
&lt;p&gt;Kim and colleagues reported that no &quot;substantial complications&quot; such as perforations or major hemorrhage occurred in the older patients, either with the CT scan or follow-up colonoscopy.&lt;/p&gt;
&lt;p&gt;They also indicated that the ratio of large to small neoplasias was similar in the older patients compared with their CT screening group as a whole. Histologic and morphologic findings were similar as well.&lt;/p&gt;
&lt;p&gt;The researchers cited the observational nature of the study, in which negative findings were not corroborated with optical colonoscopy, and its restriction to a single center as its main limitations.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;No external funding for the study was reported.&lt;/p&gt;&lt;p&gt;Kim and one co-author reported relationships with Viatronix and Medicsight and are co-founders of a company called VirtuoCTC, which produces educational materials on CT colonography.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_250"
                     title="Cancer Research &quot;Giant&quot; Lawrence Garfinkel Dies at 88"
                     score="-0.002"
                     href="http://www.medpagetoday.com/Pulmonology/Smoking/tb/18108?impressionId=1265800177475"
                     
      &lt;p&gt;Epidemiologist Lawrence Garfinkel, MA, a legendary researcher for the American Cancer Society whose work helped establish a link between cancer and smoking and other activities, died of cardiovascular disease Thursday in Seattle, Washington at 88.&lt;/p&gt;
&lt;p&gt;&quot;The American Cancer Society today mourns the loss of one of its most important historical figures,&quot; said John R. Seffrin, PhD, the society&apos;s chief executive officer.&lt;/p&gt;
&lt;p&gt;&quot;Larry Garfinkel joined the American Cancer Society as a young scientist in 1947, and for more than four decades played an instrumental role in expanding knowledge of and reducing death from smoking.&quot;&lt;/p&gt;
&lt;p&gt;Garfinkel&apos;s 1982 Cancer Prevention Study-II (CPS-II) is the largest contemporary study of tobacco and mortality, with 1.2 million participants and 77,000 data-compiling volunteers across 50 states, the District of Columbia, and Puerto Rico.&lt;/p&gt;
&lt;p&gt;CPS-II uncovered the effects of lifestyle factors, such as obesity, alcohol consumption, medications, genetic elements, that affect cancer and other chronic diseases, the analysis of which still reveals important clues about cancer today.&lt;/p&gt;
&lt;p&gt;The study also found lung cancer mortality rates in women increased five-fold from data collected in the original Cancer Prevention Study, while cancer rates among non-smoking women remained the same. This information provided strong evidence that lung cancer was almost exclusively a disease found in smokers.&lt;/p&gt;
&lt;p&gt;Garfinkel was born on January 11, 1922 in Manhattan&apos;s Lower East Side and was raised in the South Bronx.&lt;/p&gt;
&lt;p&gt;He served in the army during World War II, where he was seriously injured in northern France in August, 1944.&lt;/p&gt;
&lt;p&gt;Ultimately, Garfinkel graduated from the City College of New York and received a Masters Degree from Columbia University. He also received several honorary doctorates.&lt;/p&gt;
&lt;p&gt;Garfinkel began work for the ACS in 1947.&lt;/p&gt;
&lt;p&gt;He assisted E. Cuyler Hammond, MD, and Daniel Horn, MD, in the first ACS prospective mortality study of 187,783 males in the late 1940&apos;s by coordinating much of the field work, including training thousands of ACS volunteers in data collection techniques.&lt;/p&gt;
&lt;p&gt;Garfinkel acted as the co-principal investigator of the larger Cancer Prevention Study I (CPS-I) in 1959. The study enrolled 1 million participants across 25 states and required over 68,000 volunteers to collect data.&lt;/p&gt;
&lt;p&gt;In the 1960s, he contributed to more than two dozen major papers on the relation between smoking and health. He was co-author of one of the first reports combining epidemiology with pathology and provided some of the first direct evidence of lung damage related to smoking.&lt;/p&gt;
&lt;p&gt;Garfinkel also contributed to issuance of the landmark 1964 Surgeon General&apos;s report on smoking and health.&lt;/p&gt;
&lt;p&gt;He was appointed director of ACS research in 1979 after Hammond&apos;s retirement.&lt;/p&gt;
&lt;p&gt;Garfinkel retired from the ACS in 1989. Over the course of his career, he had contributed to more than 100 journal articles.&lt;/p&gt;
&lt;p&gt;Richard D. Klausner, MD, then-director of the National Cancer Institute, said at the time: &quot;Few individuals have contributed as much to our present-day knowledge about the disease consequences of smoking.&lt;/p&gt;
&lt;p&gt;&quot;His remarkable achievement is an important reminder what a tremendous impact an individual can make, and inspires all of us to continue the fight against cancer.&quot;&lt;/p&gt;
&lt;p&gt;Garfinkel continued to volunteer with the ACS after his retirement and taught biostatistics at the New York University Dental School.&lt;/p&gt;
&lt;p&gt;He is survived by his brothers, Harold and Melvin; his sons, Martin and Herb; a daughter-in-law, Margaret Cary, and two grandchildren.&lt;/p&gt;

    </recommendedItem>
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                     title="Stopping a Third of Cancer Deaths Is Within Reach"
                     score="-0.006"
                     href="