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    <recommendedItem id="20100101_19_425"
                     title="AAN: Industrial Cleaner Again Tied to Parkinson Risk (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAN/tb/18338?impressionId=1265784431312"
                     
      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="20100101_19_393"
                     title="SMFM: Gene Variants Linked to Preterm Labor (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/MeetingCoverage/SMFM/tb/18295?impressionId=1265784431312"
                     
      Genetic variants involved in regulating inflammation and the extracellular matrix may increase the risk of preterm birth, researchers say.&lt;br&gt;
&lt;br&gt;A single nucleotide polymorphism (SNP) in fetal interleukin-6 (&lt;em&gt;ILR6&lt;/em&gt;) and another in maternal tissue inhibitor of metalloproteinase 2 (&lt;em&gt;TIMP2&lt;/em&gt;) were each associated with a twofold increased risk of spontaneous preterm birth.&lt;br&gt;
&lt;br&gt;Roberto Romero, MD, of the National Institute of Child Health and Human Development, and colleagues reported the findings at the Society for Maternal-Fetal Medicine meeting in Chicago.&lt;/p&gt;
&lt;p&gt;&quot;The genetic makeup of both mother and fetus can contribute to the risk of premature labor,&quot; Romero told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;Our discovery . . . helps explain why some mothers have premature labor and delivery despite having optimal prenatal care.&quot;&lt;/p&gt;
&lt;p&gt;Inflammatory hormones have been shown to play a role in the labor process, and previous studies have found that a third of preterm infants are born to mothers with a silent amniotic infection.&lt;/p&gt;
&lt;p&gt;Now, the findings suggest that individual genetic variation involved in that inflammatory response may account for discrepancies in preterm births.&lt;/p&gt;
&lt;p&gt;&quot;We have a large body of evidence that proves silent infections are a frequent and important cause of premature labor,&quot; Romero said. &quot;These infections can also attack the fetus before it is born.&quot;&lt;/p&gt;
&lt;p&gt;He explained that the mother&apos;s hormones initiate the onset of labor to get rid of the infected tissue, and the fetus seeks to exit a hostile intrauterine environment that threatens its survival.&lt;/p&gt;
&lt;p&gt;To look at the mechanisms by which this process occurs, Romero and colleagues conducted a case-control study of mothers in Chile to assess genetic factors that could predispose women to spontaneous preterm labor and delivery.&lt;/p&gt;
&lt;p&gt;Patients who delivered prior to 37 weeks gestation served as cases, while women who delivered a normal neonate at term served as controls. There were 223 mothers and 179 fetuses in the case group, and 599 mothers and 628 fetuses in the control group.&lt;/p&gt;
&lt;p&gt;The researchers subsequently examined 190 candidate genes and 775 SNPs.&lt;/p&gt;
&lt;p&gt;They found that the strongest fetal single-locus association with risk of spontaneous preterm birth was in &lt;em&gt;ILR6&lt;/em&gt;, (OR 2.07, 95% CI 1.42 to 3.02,&lt;em&gt; P&lt;/em&gt;=0.0001).&lt;/p&gt;
&lt;p&gt;The strongest maternal single-locus association with spontaneous preterm labor and delivery was in tissue inhibitor of metalloproteinase &lt;em&gt;TIMP2&lt;/em&gt; (OR 1.98, 95% CI 1.38 to 2.83, &lt;em&gt;P&lt;/em&gt;=0.0002). This gene is involved in regulating the extracellular matrix, which holds cells within tissues.&lt;/p&gt;
&lt;p&gt;The associations remained significant after controlling for multiple comparisons, Romero said.&lt;/p&gt;
&lt;p&gt;Global haplotype analysis also indicated an association between a fetal DNA variant in insulin-like growth factor 2 (&lt;em&gt;P&lt;/em&gt;=0.004) as well as maternal alpha 3 type IV collagen isoform 1 (&lt;em&gt;COL4A3&lt;/em&gt;) (&lt;em&gt;P&lt;/em&gt;=0.007).&lt;/p&gt;
&lt;p&gt;&quot;Some women and fetuses carry gene variants that predispose them to the early onset of labor,&quot; Romero said.&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 researchers 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="20090101_4_315"
                     title="AAN: New Analysis Reverses Thinking on Estrogen and Alzheimer&apos;s"
                     score="-0.006"
                     href="