<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_438"
                     title="Rituximab Shows Promise in Scleroderma (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/tb/18352?impressionId=1265766117656"
                     
      &lt;p&gt;Rituximab (Rituxan) improved lung function in patients with scleroderma, a small proof-of-principle study found.&lt;/p&gt;
&lt;p&gt;At one year, patients randomized to receive rituximab had a median 10.25% increase in forced vital capacity (FVC) compared with baseline, while those who received standard treatment had a deterioration of 5.04% (&lt;em&gt;P&lt;/em&gt;=0.002), according to Dimitrios Daoussis, MD, and colleagues from the University of Patras in Greece.&lt;/p&gt;
&lt;p&gt;There also was a significant 19.46% increase in diffusing capacity of carbon monoxide (DL&lt;sub&gt;co&lt;/sub&gt;) in the rituximab-treated patients, while the controls showed deterioration of 7.5% (&lt;em&gt;P&lt;/em&gt;=0.023), the researchers reported in the February issue of &lt;em&gt;Rheumatology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Interstitial lung disease is a common manifestation of diffuse scleroderma and represents the disease component that dictates prognosis because it can be progressive and typically responds poorly to treatment. Animal and human studies have suggested a possible pathogenic role for B cells in the disease.&lt;/p&gt;
&lt;p&gt;There have been a few reports of clinical and histologic improvements in scleroderma and in graft-versus-host disease (which shares some features with scleroderma) after treatment with the B-cell depleting monoclonal antibody rituximab.&lt;/p&gt;
&lt;p&gt;These encouraging early findings led Daoussis and colleagues to undertake an open-label, controlled study that included 14 patients with diffuse disease.&lt;/p&gt;
&lt;p&gt;Median age was 55 and mean disease duration was seven years.&lt;/p&gt;
&lt;p&gt;All patients continued their standard medications, which included various agents such as prednisone, bosentan (Tracleer), mycophenolate mofetil (CellCept), and cyclophosphamide.&lt;/p&gt;
&lt;p&gt;Those randomized to rituximab treatment also underwent four weekly pulses of the drug (375 mg/m&lt;sup&gt;2&lt;/sup&gt;) at baseline and six months later.&lt;/p&gt;
&lt;p&gt;By one year, the mean FVC in the rituximab group had risen from 68.13% of normal predicted value based on age, sex, and height, to 75.63% (&lt;em&gt;P&lt;/em&gt;=0.0018), while FVC in the control group fell nonsignificantly from 86% of normal to 81.67%.&lt;/p&gt;
&lt;p&gt;In the rituximab group, DL&lt;sub&gt;co&lt;/sub&gt; increased from a mean of 52.25% of normal at baseline to 62% (&lt;em&gt;P&lt;/em&gt;=0.017) at one year, while the controls decreased nonsignificantly from 65.33% to 60.17%.&lt;/p&gt;
&lt;p&gt;None of the patients treated with rituximab experienced worsening of FVC or DL&lt;sub&gt;co&lt;/sub&gt;, whereas lung function deteriorated in five controls.&lt;/p&gt;
&lt;p&gt;&quot;We should note, however, that patients in the control group tended to have more early disease and better lung function parameters (although not statistically different from the [rituximab] group) making them more likely to deteriorate over the time of the study,&quot; the investigators commented.&lt;/p&gt;
&lt;p&gt;Skin manifestations of the disease also showed improvements in the rituximab group. Skin thickening, as measured by the Modified Rodnan Skin Score, improved by 39.25% in the rituximab group and by 20.80% in the control group, a difference that was not statistically significant.&lt;/p&gt;
&lt;p&gt;Skin fibrosis also improved by a median of 38.33%, while it worsened by 5.23% in controls.&lt;/p&gt;
&lt;p&gt;Histologic improvement was seen in four of the rituximab-treated patients, corresponding with clinical benefits. One patient in the active treatment group had a significant reduction of fibrosis in both the papillary and reticular dermis, accompanied by an almost complete resolution of skin lesions.&lt;/p&gt;
&lt;p&gt;Improvement in skin fibrosis was most common in patients who had evidence of B-cell depletion in the skin.&lt;/p&gt;
&lt;p&gt;Overall function, as evaluated by the Health Assessment Questionnaire, improved from a median baseline score of 0.687 to 0.312 at one year (&lt;em&gt;P&lt;/em&gt;=0.03), while no change was seen in controls.&lt;/p&gt;
&lt;p&gt;The pathogenesis of scleroderma is poorly understood, according to the authors, but this study adds support to a possible role for B cells.&lt;/p&gt;
&lt;p&gt;In addition, rituximab indirectly targets T cells, which also are thought to be implicated.&lt;/p&gt;
&lt;p&gt;The authors noted potential limitations, including the study&apos;s small size and the fact that most patients had longstanding disease, had been treated with multiple immunosuppressive agents in the past, and were receiving concurrent therapies during the study.&lt;/p&gt;
&lt;p&gt;&quot;This is a proof-of-principle study that was performed in order to obtain preliminary data regarding the effect of [rituximab] on a limited number of patients,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;&quot;Our data could serve as a good starting point for the design of larger scale, multicenter studies with longer evaluation periods and especially in earlier stages of the disease,&quot; they concluded.&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, Robert W. Simms, MD, and Robert Lafyatis, MD, of Boston University, echoed concerns about the small number of patients and the lack of blinding in the study.&lt;/p&gt;
&lt;p&gt;&quot;One cannot...on the basis of this study, recommend rituximab in the routine clinical care of patients with scleroderma,&quot; the editorialists wrote.&lt;/p&gt;
&lt;p&gt;The findings will need to be replicated in a multicenter randomized trial, but &quot;do provide some hope that B-cell depletion might enhance the currently restricted therapeutic armamentarium of this disease.&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;The study was funded by the Hellenic Rheumatology Society.&lt;/p&gt;&lt;p&gt;Funding to pay Open Access publication charges was provided by Roche Hellas.&lt;/p&gt;&lt;p&gt;Authors and editorialists declared to 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_277"
                     title="Liver Cell Culture System Might Test New HCV Drugs (CME/CE)"
                     score="0.003"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/18133?impressionId=1265766117656"
                     
      &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_261"
                     title="Scrubbing Away Germs Can Backfire on Backsides (CME/CE)"
                     score="-0"
                     href="http://www.medpagetoday.com/Pediatrics/GeneralPediatrics/tb/18121?impressionId=1265766117656"
                     
      Rashes from toilet seats are once again afflicting American children, and the rare condition is often misdiagnosed, which may delay proper treatment.&lt;br&gt;
&lt;br&gt;That&apos;s the conclusion from a report based of five-cases of toilet-seat contact dermatitis investigated by researchers at Johns Hopkins University School of Medicine and reported in the Jan. 25 issue of &lt;em&gt;Pediatrics&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;While toilet-seat dermatitis is commonly thought to result from allergies to wooden seats, the report concludes that another source is plastic toilet seats cleaned with harsh detergents.&lt;/p&gt;
&lt;p&gt;&quot;This case series and previous reports have documented that toilet-seat dermatitis is much more common than previously recognized in the U.S. and around the world,&quot; Bernard A. Cohen, MD, and colleagues wrote.&lt;/p&gt;
&lt;p&gt;&quot;Furthermore, the incidence of this condition is rising in North America because of a resurgent popularity of exotic-wood toilet seats and frequent use of detergents that contain highly irritant/sensitizing compounds such as quaternary ammonium compounds, phenol, formaldehyde, etc. in public restrooms.&quot;&lt;/p&gt;
&lt;p&gt;Of the cases analyzed by the authors, two occurred in the U.S. and the other three occurred in India.&lt;/p&gt;
&lt;p&gt;Both U.S. cases were girls, a 6-year-old who had a rash for over two years before it was correctly diagnosed and a 10-year-old whose rash lasted for a year. In both cases, the rashes seemed to worsen during the school year when the girls were using school restrooms. The younger girl&apos;s dermatitis twice became infected with methicillin-resistant &lt;em&gt;Staphylococcus aureus &lt;/em&gt;and required treatment with antibiotics.&lt;/p&gt;
&lt;p&gt;After doctors determined the rashes were the result of contact with toilet seats and instructed the girls to use toilet-seat covers and apply moisturizers and topical steroids to the affected areas, the eruptions cleared up within a few weeks.&lt;/p&gt;
&lt;p&gt;The cases in India included a 14-month old boy and two girls, 12 and 10.&lt;/p&gt;
&lt;p&gt;The boy and the 12-year-old girl were both initially misdiagnosed with ringworm and unsuccessfully treated with clotrimazole cream. The other girl was unsuccessfully treated with ayurvedic and homeopathic topical medications before doctors diagnosed toilet-seat dermatitis. Two of the children were instructed to use soaps that only exacerbated the problem.&lt;/p&gt;
&lt;p&gt;In all three cases, the rashes cleared up with some combination of topical steroids, using toilet-seat covers, replacing the household toilet seat, and limiting time on the toilet.&lt;/p&gt;
&lt;p&gt;The authors distinguished between two types of toilet-seat dermatitis: allergic contact dermatitis, the better described form of the condition, in which a patient develops allergy to wooden toilet seats, and irritant contact dermatitis, in which the rashes result from contact with harsh detergents used on plastic toilet seats.&lt;/p&gt;
&lt;p&gt;They noted that detergents used in public restrooms and in hospitals are potentially more irritating to the skin than those used at home and that alkaline detergents are more likely to cause skin irritation than acidic detergents, because they perturb the body&apos;s natural acidic environment.&lt;/p&gt;
&lt;p&gt;Toilet-seat dermatitis was first identified as an external skin rash in 1927. Exposure to wooden toilet seats and associated varnish, lacquers, and paints led to sensitization and development of an allergic contact dermatitis.&lt;/p&gt;
&lt;p&gt;The condition nearly disappeared in the U.S. in 1980s and 1990s, after public facilities and homeowners in the U.S. changed from wooden to plastic toilet seats and sanitary seat covers became readily available.&lt;/p&gt;
&lt;p&gt;However, in recent years the number of cases has grown as a result of homeowners installing toilet seats made of exotic woods and the increased use of harsh toilet seat detergents.&lt;/p&gt;
&lt;p&gt;Most reports have focused on adults with rashes, but little previous attention has focused on the condition in children. &quot;In this case series we describe toilet-seat contact dermatitis in children and underscore a typical history and physical findings that we hope will aid clinicians in recognizing this disease,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;&quot;It is important to underscore that regular use of toilet-seat covers is the key to success in treatment,&quot; the authors wrote. &quot;Such seat covers can be purchased at any major retailer such as Walmart or online.&lt;/p&gt;
&lt;p&gt;As an alternative, newspaper cutouts could be used to provide barrier protection. Although it is possible to develop an allergy to toilet-seat covers, none have been reported thus far in the literature.&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;The authors reported no sources of funding or financial 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_217"
                     title="Herpes Therapy Doesn&apos;t Bar HIV Transmission (CME/CE)"
                     score="-0.004"
                     href="http://www.medpagetoday.com/HIVAIDS/HIVAIDS/tb/18071?impressionId=1265766117656"
                     
      &lt;p&gt;Treating herpes has no effect on the transmission of HIV among discordant couples, researchers said.&lt;/p&gt;
&lt;p&gt;The lack of efficacy was found in a large, randomized clinical trial despite significant reductions in HIV viral load among those treated for herpes simplex-2 (HSV-2), according to Connie Celum, MD, of the University of Washington, and colleagues.&lt;/p&gt;
&lt;p&gt;Researchers will have to look for new ways to prevent transmission among discordant couples (in which one partner has HIV and the other does not), Celum and colleagues concluded online in the&lt;em&gt; New England Journal of Medicine.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;The study comes after earlier trials also showed that treating HSV-2 with the antiviral acyclovir (Zovirax) did not lower the risk of getting HIV. (See &lt;a href=&quot;http://www.medpagetoday.com/HIVAIDS/HIVAIDS/9884&quot; mce_href=&quot;http://www.medpagetoday.com/HIVAIDS/HIVAIDS/9884&quot; target=&quot;_blank&quot;&gt;Herpes Treatment No Help in Preventing HIV&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;The trials  --  and the current study  --  had their origins in epidemiological and laboratory observations that having an HSV-2 infection increased the risk of contracting HIV.&lt;/p&gt;
&lt;p&gt;Researchers reasoned that a converse effect might also be true  --  treating HSV-2 in HIV-negative people might reduce their risk of infection.&lt;/p&gt;
&lt;p&gt;The reasoning was bolstered by clinical trials showing that treating HSV-2 in HIV-positive people lowered their viral load.&lt;/p&gt;
&lt;p&gt;In the current study, that effect also occurred. HIV-positive volunteers treated with acyclovir saw, on average, a reduction in plasma concentration of HIV by 0.25 log&lt;sub&gt;10&lt;/sub&gt; copies per milliliter compared with members of the placebo group. The difference was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001.&lt;/p&gt;
&lt;p&gt;But transmission among the couples was not affected, implying that a greater reduction in viral load is needed, the researchers said.&lt;/p&gt;
&lt;p&gt;The study, randomized and placebo-controlled, included 3,408 couples in Africa in which only one of the partners had HIV (but was not taking antiretroviral therapy) and also had an HSV-2 infection.&lt;/p&gt;
&lt;p&gt;The outcome was first reported at the Cape Town meeting of the International AIDS Society last year (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/IAS/15242&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/IAS/15242&quot; target=&quot;_blank&quot;&gt;IAS: Acyclovir Flops in Preventing HIV Transmission&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;The primary outcome was transmission between partners, verified by genetic sequencing of the virus.&lt;/p&gt;
&lt;p&gt;Transmission between partners was verified in 84 of the 132 recorded cases of transmission, the researchers said, and they were evenly divided  --  41 among those getting the drug and 43 in the placebo group.&lt;/p&gt;
&lt;p&gt;On the other hand, the use of the drug reduced the occurrence of herpes lesions by 73%, which was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001.&lt;/p&gt;
&lt;p&gt;The reduction of herpes lesions suggests that the drug was being used, the researchers said, and therefore that the lack of efficacy against HIV was not a result of nonadherence to acyclovir.&lt;/p&gt;
&lt;p&gt;Overall, the rate of HIV transmission in the study was 2.7 cases per 100 person-years, markedly lower than earlier observations. The researchers attributed that to such interventions as monthly counseling on risk reduction and free condoms.&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 had support from the Bill and Melinda Gates Foundation, as well as the University of Washington, the National Institute of Allergy and Infectious Diseases, Gen-Probe, and the National Institute of Mental Health.&lt;/p&gt;&lt;p&gt;Celum reported financial links with GlaxoSmithKline and several other authors reported links with various pharamceutical companies.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_830"
                     title="California Judge Rules Tattoo Inks Must Carry Health Warnings"
                     score="-0.006"
                     href="