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    <recommendedItem id="20100101_19_452"
                     title="Study Backs Late Cardiotoxicity of Childhood Cancer Treatment (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/HematologyOncology/OtherCancers/tb/18384?impressionId=1265803424198"
                     
      A childhood cancer survivor&apos;s risk of dying from cardiovascular causes rises with the dose of radiation his heart received during treatment, researchers in France and the U.K. affirmed.&lt;br&gt;
&lt;br&gt;Those whose hearts were exposed had a 60% higher risk of cardiovascular death than the general population, even at a dose of 1 Gy (95% CI 20% to 250%), according to Florent de Vathaire, PhD, of L&apos;Institut National de la Sant&amp;#233; et de la Recherche M&amp;#233;dicale in Paris, and colleagues.&lt;br&gt;
&lt;br&gt;The risk jumped to 12.5-fold for a cumulative radiation dose to the heart of 5 to 14.9 Gy, and to 14.9-fold for a dose of more than 15 Gy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01 for trend), the researchers reported online in the &lt;em&gt;Journal of Clinical Oncology&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;The notion that exposing the heart to radiation increases the risk of cardiovascular disease and death is not surprising, according to an accompanying editorial.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;However, this study examined cardiovascular mortality effects of both the dose of radiation and the dose of anthracyclines given to childhood cancer victims in the same cohort.&lt;/p&gt;
&lt;p&gt;That&apos;s something previous studies haven&apos;t done, according to editorialists Steven E. Lipshultz, MD, of the University of Miami and Holtz Children&apos;s Hospital in Miami, and M. Jacob Adams, MD, MPH, of the University of Rochester, N.Y.&lt;/p&gt;
&lt;p&gt;&quot;These are pretty profound findings,&quot; Lipshultz told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;These are the exact concerns we&apos;ve had based on careful subclinical assessments of how the heart in these survivors has been working.&quot;&lt;/p&gt;
&lt;p&gt;His group was one of the first to report that survivors of childhood cancer faced not only acute cardiotoxicity from treatment, but also late cardiac effects.&lt;/p&gt;
&lt;p&gt;As more effective treatment for childhood cancers came into play, the dramatic jump in survival rates  --  from less than 50% in the mid-1970s to 80% today  --  yielded a large enough population of survivors to make chronic issues from treatment apparent, Lipshultz noted.&lt;/p&gt;
&lt;p&gt;&quot;It appears that for some of these survivors we have substituted one fatal disease of childhood  --  cancer  --  for another fatal disease of early adult life,&quot; he said.&lt;/p&gt;
&lt;p&gt;de Vathaire&apos;s group studied a cohort of 4,122 French and British children diagnosed with childhood solid cancer between 1942 and 1986 and who survived at least five years.&lt;/p&gt;
&lt;p&gt;Over an average of 27 years of follow-up, they were at 8.3-fold higher risk of dying from any cause compared with the general populations in France and the U.K. (95% CI 7.6 to 9.0).&lt;/p&gt;
&lt;p&gt;The majority of these excess deaths occurred early after diagnosis, five to nine years afterward in this analysis  --  in which all patients survived to five years.&lt;/p&gt;
&lt;p&gt;Based on just 32 deaths from cardiovascular diseases in the cohort, the childhood cancer survivors experienced five times the cardiovascular mortality (95% CI 3.3 to 6.7) expected from the general population (1.7% cumulative at 35 years versus 0.3%).&lt;/p&gt;
&lt;p&gt;This elevation in risk was similar to that seen in large studies from the U.S. and Nordic countries, suggesting generalizability of the results, Lipshultz said.&lt;/p&gt;
&lt;p&gt;Radiation therapy also conferred a 5.0-fold elevation in risk of cardiovascular disease-related death (95% CI 1.2 to 21.4).&lt;/p&gt;
&lt;p&gt;Like radiation, a higher cumulative dose of anthracycline chemotherapy also increased risk of dying from cardiac diseases, compared with the general population (RR 4.4 for a dose over 360 mg/m&lt;sup&gt;2&lt;/sup&gt;, 95% CI 1.3 to 15.3).&lt;/p&gt;
&lt;p&gt;However, radiotherapy and chemotherapy did not appear to interact for cardiovascular mortality (&lt;em&gt;P&lt;/em&gt;=0.4).&lt;/p&gt;
&lt;p&gt;Notably, the vinca alkaloids were also significantly linked to cardiovascular disease-related death risk among childhood cancer survivors, even after adjustment for sex, treatment period, age at diagnosis, follow-up, and all other treatment modalities (RR 3.6, 95% CI 1.0 to 12.9).&lt;/p&gt;
&lt;p&gt;Currently, guidelines support regular long-term cardiovascular screening for childhood cancer survivors who received anthracycline-based chemotherapy but provide little to no direction for those treated with nonanthracycline chemotherapy or radiation, Lipshultz noted.&lt;/p&gt;
&lt;p&gt;These results suggested all three groups should be getting cardiac follow-up, he told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;However, because other research has suggested that these individual treatments affect the heart in different ways, such as diastolic rather than systolic dysfunction with radiotherapy, screening modalities may need to account for this as well, he said.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that cardiovascular disease was probably under-reported as a cause of death in the cohort.&lt;/p&gt;
&lt;p&gt;&quot;Indeed, 15 of the deaths classified as results of cancer as the principal cause had cardiovascular diseases as the immediate cause,&quot; they wrote.&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;The study was supported by the Ligue Nationale Contre le Cancer; the Programme Hospitalier de Recherche Clinique; the Agence Fran&amp;#231;aise de S&amp;#233;curit&amp;#233; Sanitaire et Produit de Sant&amp;#233;; Electricit&amp;#233; de France; the Wyeth Foundation for childhood and adolescent health; and a grant from the Foundation of France.&lt;/p&gt;&lt;p&gt;The researchers reported no conflicts of interest.&lt;/p&gt;&lt;p&gt;The editorialists reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <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=1265803424198"
                     
      &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_250"
                     title="Cancer Research &quot;Giant&quot; Lawrence Garfinkel Dies at 88"
                     score="-0"
                     href="http://www.medpagetoday.com/Pulmonology/Smoking/tb/18108?impressionId=1265803424198"
                     
      &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>
    <recommendedItem id="20090101_1_481"
                     title="Stopping a Third of Cancer Deaths Is Within Reach"
                     score="-0.006"
                     href="