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    <recommendedItem id="20100101_19_425"
                     title="AAN: Industrial Cleaner Again Tied to Parkinson Risk (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAN/tb/18338?impressionId=1265777162119"
                     
      TORONTO  --  The degreasing agent trichloroethylene (TCE) has been linked to increased rates of Parkinson&apos;s disease among industrial workers in yet another study, this time involving a large, well-studied group of World War II veterans.&lt;br&gt;
&lt;br&gt;Parkinson&apos;s disease developed in individuals with occupational exposure to TCE at more than five times the rate seen in those without such exposure (odds ratio 5.5, 95% CI 1.02 to 30), reported Samuel Goldman, MD, of the Parkinson&apos;s Institute in Sunnyvale, Calif.&lt;br&gt;
&lt;br&gt;Goldman described the research in a phone interview with &lt;em&gt;MedPage Today&lt;/em&gt;. It&apos;s scheduled for presentation here in April at the American Academy of Neurology&apos;s annual meeting.&lt;br&gt;
&lt;br&gt;A previous study in 2008 had fingered TCE as the most likely culprit behind a cluster of Parkinson&apos;s disease cases afflicting workers at a single industrial plant. (See &lt;a href=&quot;http://www.medpagetoday.com/Geriatrics/ParkinsonsDisease/7894&quot; mce_href=&quot;http://www.medpagetoday.com/Geriatrics/ParkinsonsDisease/7894&quot; target=&quot;_blank&quot;&gt;Trichloroethylene Implicated as Risk for Parkinsonism&lt;/a&gt;)&lt;p&gt;&lt;/p&gt;
&lt;p&gt;Also, Goldman said, animal studies have found that TCE is selectively toxic to nigral dopaminergic neurons, the same type of nerve cell that progressively dies off in Parkinson&apos;s disease. He said the chemical&apos;s activity in rodent brains is very similar to that of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a dopaminergic neurotoxin commonly used to simulate Parkinson&apos;s disease in preclinical research.&lt;/p&gt;
&lt;p&gt;Goldman said the new study was the first population-based analysis to link TCE to the disease.&lt;/p&gt;
&lt;p&gt;It focused on 198 twin pairs in the National Academy of Sciences-National Research Council&apos;s World War II Twins Cohort, which comprises some 16,000 twin pairs overall.&lt;/p&gt;
&lt;p&gt;Members of the all-male cohort, who were born from 1917 to 1927 and served in the war, have been followed since the 1960s. Occupational histories for participants are available along with medical records from the VA healthcare system.&lt;/p&gt;
&lt;p&gt;In those pairs chosen for the current study, records showed that one twin had developed Parkinson&apos;s disease and the other had not. This design largely eliminates genetics as a confounding factor in the analysis.&lt;/p&gt;
&lt;p&gt;Goldman explained that occupational histories for each participant were reviewed by a blinded industrial hygienist and a preventive medicine physician to identify likely exposures to TCE and four other industrial chemicals: xylene, toluene, carbon tetrachloride, and tetrachloroethylene.&lt;/p&gt;
&lt;p&gt;As a single source of exposure, only TCE was significantly associated with development of Parkinson&apos;s disease, Goldman said.&lt;/p&gt;
&lt;p&gt;People working as aircraft mechanics, machinists, plumbers, and electricians likely had regular exposure to TCE, Goldman said. The chemical was commonly used as a &quot;spot&quot; cleaner to remove grease and oils from metal surfaces. It was also used for a time as a dry cleaning solvent, although tetrachloroethylene was more common for that purpose.&lt;/p&gt;
&lt;p&gt;Goldman said no increased risk was seen with xylene or toluene, but there were near-significant trends toward increased Parkinson&apos;s disease risk from carbon tetrachloride and tetrachloroethylene: &lt;ul&gt; &lt;li&gt;Carbon tetrachloride: OR 2.8 (95% CI 0.97 to 7.8)&lt;/li&gt; &lt;li&gt;Tetrachloroethylene: OR 9.0 (95% CI 0.78 to 103)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Twins exposed to either TCE or tetrachloroethylene were at significantly increased risk, with an odds ratio of 8.1 (95% CI 1.43 to 43) relative to individuals with no exposure to either chemical.&lt;/p&gt;
&lt;p&gt;Goldman said the analysis also examined whether duration of exposure was associated with increased risk. He said the results were in the same pattern as for the yes-no exposure analysis, but the findings were very uncertain because of the relatively small sample size.&lt;/p&gt;
&lt;p&gt;Occupational histories were available for only 99 of the 198 discordant twin pairs and some of the information was obtained by proxy rather than from the participant himself.&lt;/p&gt;
&lt;p&gt;Because of the wide confidence intervals even for the yes-no exposure analysis, the findings need confirmation in a larger study, he said, noting that the best approach would be a cohort study involving people with known, long-term exposure to TCE, compared with well-chosen controls.&lt;/p&gt;
&lt;p&gt;&quot;The study wouldn&apos;t have to be large,&quot; Goldman said. He estimated that 1,000 to 2,000 participants would be adequate to determine if the connection to Parkinson&apos;s disease is real.&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 funded by the National Institute of Neurological Disorders and Stroke, the Valley Foundation, and the James and Sharron Clark Family Fund.&lt;/p&gt;&lt;p&gt;No potential conflicts of interest were reported.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_1300"
                     title="AAN: Another Polyomavirus Appears Reactivated with Natalizumab"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAN/tb/13950?impressionId=1265777162119"
                     
       SEATTLE, April 28 -- The JC polyomavirus responsible for progressive multifocal leukoencephalopathy (PML) may not be the only such virus reactivated by natalizumab (Tysabri).
              &lt;p&gt; 
              &lt;p&gt;In a study of 57 patients receiving natalizumab for relapsing-remitting multiple sclerosis, twelve (22%) saw reactivation of the BK polyomavirus, which can cause nephropathy and hemorrhagic cystitis, reported Roisin Lonergan, M.S., a neurology fellow at St. Vincent&apos;s Hospital in Dublin, Ireland.
              &lt;p&gt; 
              &lt;p&gt;No cases of clinical disease or other overt adverse effects were seen in the study, which began in January 2007, Dr. Lonergan said in a poster presentation here at the American Academy of Neurology&apos;s annual meeting.
              &lt;p&gt; 
              &lt;p&gt;Nevertheless, monitoring patients taking natalizumab for BK polyomavirus reactivation and for renal dysfunction may be warranted, she suggested.
              &lt;p&gt; 
              &lt;p&gt;The occurrence of three cases of PML, which is often fatal, forced natalizumab off the market in 2005, just a few months after its initial approval. Marketing resumed in June 2006 under a restricted-access program intended to prevent additional PML cases.
              &lt;p&gt; 
              &lt;p&gt;Natalizumab is a monoclonal antibody against the alpha4-integrin adhesion molecule. It is believed that this mechanism somehow allows latent infections with the JC polyomavirus, which are extremely common, to become active again.
              &lt;p&gt; 
              &lt;p&gt;But the JC virus responsible for PML is not the only common polyomavirus capable of causing significant illness, prompting the Irish study of possible BK virus reactivation.
              &lt;p&gt; 
              &lt;p&gt;Such reactivation has been seen in patients receiving kidney transplants and follow-up immunosuppressant treatment. Nephropathy caused by the virus is a frequent cause of graft failure in these patients.
              &lt;p&gt; 
              &lt;p&gt;Dr. Lonergan and colleagues prospectively evaluated 57 patients starting treatment with natalizumab.
              &lt;p&gt; 
              &lt;p&gt;They found BK virus in urine in three of 36 baseline samples prior to starting on the drug.
              &lt;p&gt; 
              &lt;p&gt;Subsequently, the virus was found in urine or blood samples in 12 patients, following a mean of 11.2 natalizumab doses (range 1 to 23).
              &lt;p&gt; 
              &lt;p&gt;The researchers also identified JC virus reactivation on one patient after a single dose. PML did not develop.
              &lt;p&gt; 
              &lt;p&gt;Nor did any cases of renal dysfunction occur, the researchers found. Renal profiles remained within normal limits in all patients.
              &lt;p&gt; 
              &lt;p&gt;Dr. Lonergan said the latter finding should be reassuring to patients on natalizumab therapy.
              &lt;p&gt; 
              &lt;p&gt;Absolute CD4- and CD8-positive cell counts did not decrease significantly overall with natalizumab.
              &lt;p&gt; 
              &lt;p&gt;However, four of the patients with BK virus reactivation showed transient reductions in CD4-positive cell counts shortly before the virus was detected in urine.
              &lt;p&gt; 
              &lt;p&gt;In three of these patients, moreover, a return of CD4-positive cell counts to baseline values paralleled suppression of BK virus replication.
              &lt;p&gt; 
              &lt;p&gt;Lily Jung, M.D., a neurologist at Swedish Neuroscience Institute in Seattle, who was not involved with the study, said the findings could be significant.
              &lt;p&gt; 
              &lt;p&gt;She noted that urinary tract infections are not uncommon in multiple sclerosis patients. But the possibility that blood in the urine might reflect hemorrhagic cystitis related to BK reactivation, rather than an ordinary urinary tract infection, is a concern.
              &lt;p&gt; 
              &lt;p&gt;&quot;They get blood in their urine, and it&apos;s very easy to . . . say it&apos;s a UTI rather than a reactivation of the polyomavirus,&quot; Dr. Jung said.
              &lt;p&gt; 
              &lt;p&gt;But she noted that no actual cases have been seen yet, a point echoed by Giancarlo Comi, M.D., a neurologist at Hospital San Raffaele in Milan, Italy, who also was not involved with the study.
              &lt;p&gt; 
              &lt;p&gt;He said BK virus reactivation was &quot;theoretically&quot; a concern, but the lack of dysfunction seen in the Irish study suggested that clinicians need not worry about it for now.
              &lt;p&gt; 
              &lt;p&gt;&quot;To link this to a new risk, to me, there is no reason [now],&quot; Dr. Comi said.
              &lt;p&gt; 
              &lt;p&gt;On the other hand, he suggested the findings could be helpful to virologists in shedding light on the dynamics of polyomaviruses.
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt; No external funding for the study was reported.
              &lt;p&gt; 
              &lt;p&gt;No potential conflicts of interest were reported by Dr. Lonergan or Dr. Jung. One co-investigator on the study reported a relationship with Biogen Idec. Dr. Comi reported relationships with Teva, Merck Serono, Bayer-Schering, Novartis, sanofi-aventis, and Biogen-Dompe.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
    </recommendedItem>
    <recommendedItem id="20090101_4_324"
                     title="AAN: Rituximab Reduces MS Lesions and Relapses"
                     score="-0.007"
                     href="