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    <recommendedItem id="20100101_19_277"
                     title="Liver Cell Culture System Might Test New HCV Drugs (CME/CE)"
                     score="0.002"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/18133?impressionId=1265806651451"
                     
      &lt;p&gt;Researchers say they can now grow liver cells that maintain their functions long enough to test potential treatments for hepatitis C.&lt;/p&gt;
&lt;p&gt;The method uses so-called &quot;micropatterned co-cultures&quot; of primary human hepatocytes and supportive stroma, according to Sangeeta N. Bhatia, MD, PhD, of MIT, and colleagues.&lt;/p&gt;
&lt;p&gt;The co-cultures were able to support the entire life cycle of hepatitis C, including infection and replication, Bhatia and colleagues reported online in the &lt;em&gt;Proceedings of the National Academy of Sciences&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Coupled with reporter systems, the co-cultures have &quot;potential as a high-throughput platform for simultaneous assessment of in vitro efficacy and toxicity&quot; of antiviral drugs, the researchers said.&lt;/p&gt;
&lt;p&gt;The lack of such a system has been a roadblock to testing potential treatments for the virus, which affects 130 million people around the world, the researchers noted in the journal.&lt;/p&gt;
&lt;p&gt;Recently, they added, researchers have been able to propagate the virus in human hepatoma cells, but those cells, among other issues, proliferate abnormally and have disturbed gene expression.&lt;/p&gt;
&lt;p&gt;To overcome those obstacles, the researchers turned to primary hepatocytes, which would make a better test system, except that they are notoriously hard to maintain in culture.&lt;/p&gt;
&lt;p&gt;To form the co-cultures, Bhatia and colleagues seeded multi-well plates with human hepatocytes, followed several hours later by murine fibroblasts.&lt;/p&gt;
&lt;p&gt;&quot;If you just put cells on a surface in an unorganized way, they lose their function very quickly,&quot; Bhatia said in a statement. &quot;If you specify which cells sit next to each other, you can extend the lifetime of the cells and help them maintain their function.&quot;&lt;/p&gt;
&lt;p&gt;In a series of experiments, Bhatia and colleagues found:&lt;ul&gt; &lt;li&gt;Pseudoparticles bearing the hepatitis C glycoproteins E1 and E2 were able to infect between 1% and 3% of the hepatocytes, but did not infect the fibroblasts.&lt;/li&gt; &lt;li&gt;A hepatitis C virus modified to express a fluorescent protein persistently replicated over a two-week period.&lt;/li&gt; &lt;li&gt;Infectious virus was found in the co-culture supernatant from four through 12 days after initial infection.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The researchers also tested some possible therapeutics, including antibodies against viral entry factors and viral protease inhibitors, and were able to show effects on replication of hepatitis C.&lt;/p&gt;
&lt;p&gt;They were also able to test two or more drugs simultaneously to show the feasibility of combination drug studies using the system.&lt;/p&gt;
&lt;p&gt;Although the system is &quot;an important step forward,&quot; Bhatia and colleagues said, the co-cultures have some limitations, including the relatively inefficient uptake of virus.&lt;/p&gt;
&lt;p&gt;But they concluded that the co-cultures have the potential to be a &quot;highly valuable system for studies of (hepatitis C) biology.&quot;&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;This study had support from the Greenberg Medical Research Institute, the Ellison Medical Foundation, the Starr Foundation, the Ronald A. Shellow Memorial Fund, the Richard Salomon Family Foundation, and the NIH. The researchers said they had no conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_216"
                     title="Novel Treatment Cuts Recurrence of &lt;em&gt;C. difficile&lt;/em&gt; (CME/CE)"
                     score="-0.002"
                     href="http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/tb/18067?impressionId=1265806651451"
                     
      &lt;p&gt;Adding two investigational monoclonal antibodies to standard antibiotics reduced the rate of recurrent &lt;em&gt;Clostridium difficile &lt;/em&gt;infection, a phase II randomized controlled trial showed.&lt;/p&gt;
&lt;p&gt;Patients who received a single infusion with the two monoclonal antibodies were significantly less likely to have a recurrence through 84 days of follow-up than those who received placebo (7% versus 25%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001), according to Israel Lowy, MD, PhD, of Medarex in Princeton, N.J., and colleagues.&lt;/p&gt;
&lt;p&gt;Adverse events occurred at similar rates in the two groups, the researchers reported in the Jan. 21 &lt;em&gt;New England Journal of Medicine.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;Medarex is a subsidiary of Bristol-Myers Squibb focused on developing fully human antibody-based therapies.&lt;/p&gt;
&lt;p&gt;&quot;The trial results are impressive,&quot; Lorraine Kyne, MD, MPH, of University College Dublin, wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;Although monoclonal antibodies probably would not be used as first-line treatment, she said, &quot;this novel nonantibiotic approach to secondary prevention is likely to offer hope to physicians and patients battling &lt;em&gt;C. difficile&lt;/em&gt; infection.&quot;&lt;/p&gt;
&lt;p&gt;Agreeing was Neil Fishman, MD, of the University of Pennsylvania, who called the findings &quot;very encouraging and very exciting&quot; in an interview.&lt;/p&gt;
&lt;p&gt;However, he noted that the safety of the treatment would have to be established in a much higher number of patients.&lt;/p&gt;
&lt;p&gt;The proper place for the antibody therapy in the management of &lt;em&gt;C. difficile&lt;/em&gt; needs to be established in future studies as well, said Fishman, who is also chair of the antimicrobial resistance work group for the Infectious Diseases Society of America.&lt;/p&gt;
&lt;p&gt;Whether it should be administered during a first episode or at first recurrence is an open question, he said, and the answer will depend both on phase III results and cost, which tends to be high for monoclonal antibody therapies.&lt;/p&gt;
&lt;p&gt;Still, he said, &quot;All disclaimers aside, I think this is a very significant, important study and an important new development in the management of &lt;em&gt;C. difficile&lt;/em&gt;.&quot;&lt;/p&gt;
&lt;p&gt;Lowy&apos;s group wrote in the journal that new therapies are needed to manage &lt;em&gt;C. difficile&lt;/em&gt;, which is increasing in prevalence and severity.&lt;/p&gt;
&lt;p&gt;Some 15% to 30% of patients will have a recurrence despite antibiotic treatment, which itself puts patients at risk for &lt;em&gt;C. difficile&lt;/em&gt; diarrhea or colitis. Broad-spectrum antibiotics knock the infection down but do not allow for the re-establishment of normal bowel flora.&lt;/p&gt;
&lt;p&gt;In addition, a hypervirulent strain  --  called BI/NAP1/027 --  has emerged in several large, deadly outbreaks in the U.S., Canada, and Europe. (See &lt;a href=&quot;http://www.medpagetoday.com/InfectiousDisease/PublicHealth/2254&quot; mce_href=&quot;http://www.medpagetoday.com/InfectiousDisease/PublicHealth/2254&quot; target=&quot;_blank&quot;&gt;Virulent Strain of &lt;em&gt;C. Difficile&lt;/em&gt; Called Cause of Diarrhea Outbreaks&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;The two fully human, monoclonal antibodies evaluated by Lowy&apos;s group  --  one each against &lt;em&gt;C. difficile&lt;/em&gt; toxins A (CDA1) and B (CDB1)  --  showed efficacy in a hamster model and safety in healthy people.&lt;/p&gt;
&lt;p&gt;To further establish safety and efficacy, the researchers enrolled 200 patients with &lt;em&gt;C. difficile&lt;/em&gt; infection at 30 sites in the U.S. and Canada and randomized half to receive the antibodies and half to placebo.&lt;/p&gt;
&lt;p&gt;The antibodies were given together in a single infusion, both at a dose of 10 mg/kg.&lt;/p&gt;
&lt;p&gt;All patients were also receiving either metronidazole or vancomycin.&lt;/p&gt;
&lt;p&gt;In the antibody group, all cases of recurrence within 84 days of infusion occurred in patients who had been hospitalized during their initial episode.&lt;/p&gt;
&lt;p&gt;Echoing the primary finding, the rate of recurrence was significantly lower following the antibody infusion among the subgroup of patients who had had more than one previous episode of &lt;em&gt;C. difficile&lt;/em&gt; infection (7% versus 38%, &lt;em&gt;P&lt;/em&gt;=0.006).&lt;/p&gt;
&lt;p&gt;The recurrence rate also tended to be lower in the antibody group among patients who had the epidemic BI/NAP1/027 strain (8% versus 32%), although the difference did not reach statistical significance (&lt;em&gt;P&lt;/em&gt;=0.06).&lt;/p&gt;
&lt;p&gt;During the initial episode, the antibody treatment did not shorten the length of hospitalization or the time to resolution or severity of diarrhea compared with placebo.&lt;/p&gt;
&lt;p&gt;The antibodies were not immunogenic.&lt;/p&gt;
&lt;p&gt;Safety from the monoclonal antibody infusion was not a concern. Adverse events during infusion or within the next two hours occurred in 15 patients in the antibody group and 10 in the placebo group. All were mild to moderate, with headache the most common.&lt;/p&gt;
&lt;p&gt;During follow-up, at least one serious adverse event was reported by 18 patients in the antibody group and 28 in the placebo group, a difference that was not statistically significant (&lt;em&gt;P&lt;/em&gt;=0.09).&lt;/p&gt;
&lt;p&gt;There were 15 deaths during the study  --  seven in the antibody group and eight in the placebo group. None was attributed to the study drug.&lt;/p&gt;
&lt;p&gt;Lowy stressed that larger studies are needed to confirm the findings.&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 MassBiologics and Medarex, which employs two of the study authors.&lt;/p&gt;&lt;p&gt;Lowy and one of his co-authors reported being employees of Medarex and having an equity interest in the company. Lowy reported being named as a co-inventor on relevant patents with all rights or royalties assigned to Medarex and having an equity interest in Merck. His co-authors reported being named as co-inventors on relevant patents and sharing a partial interest in them, and having relationships with MassBiologics, Medarex, Robert Michael Associates, ViroPharma, GOJO Industries, Salix, Schering-Plough, Cepheid, Merck, TheraDoc, Optimer, and Genzyme.&lt;/p&gt;&lt;p&gt;Kyne reported receiving salary support from a Clinician Scientist Award from the Health Research Board, Ireland.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_2_771"
                     title="AASLD: Proton Pump Inhibitors May Be Problematic for Cirrhosis Patients"
                     score="-0.005"
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