IN THE NEWS
Caring Ambassadors Hepatitis C Program launches internet-based Hep C Discussion PointTM to assist people living with hepatitis C
“The Caring Ambassadors Hepatitis C Program (CAP Hepatitis C), a national nonprofit organization, announces the Internet release of its new interactive medical management tool, Hep C Discussion Point™ at www.HepCChallenge.org. Hep C Discussion Point™ takes the user through a guided series of questions about their hepatitis C experience. Custom-built software analyzes the user's responses and generates a report with information and topics specific to the user's inputs. The report is designed to be used as both a learning tool for the patient and as a guide to facilitate communication and enhance the health care partnership between people living with hepatitis C and their doctors.”[truncated]
Researchers develop a process to disrupt hepatitis C virion production
“HCV is a significant human pathogen, infecting more than three percent of the world's population. The incidence of infection in the United States has been estimated to be as high as 4 million cases. In the March issue of the journal PLoS Pathogens, Timothy Tellinghuisen, an assistant professor in the Department of Infectology at Scripps Florida, and his colleagues describe how they used mutations of the viral NS5A phosphoprotein to disrupt virus particle production at an early stage of assembly. NS5A has long been proposed as a regulator of events in the HCV life cycle, but exactly how it orchestrates these events has been unclear.” [truncated]
Risk of hepatitis C from tattoo art not sharply defined, experts say
“While there is a dearth of strong evidence of a link between getting a tattoo and becoming infected with hepatitis C, the potential is there, said Wendy Dillon, coordinator for the state's adult viral hepatitis prevention program. “Here's what I say,” she said at a recent meeting about safe tattooing. “If there is blood-to-blood contact, there is potential.” While hepatitis A and B are vaccine preventable, no such treatment yet exists for hepatitis C. And no vaccine is likely to show up soon, Dillon said. “The virus mutates so quickly.””[truncated]
Bexar County awaits AG opinion on needle-exchange program.
Project to prevent spread of disease legal only in Bexar, yet isn't
“SAN ANTONIO - Bill Day uses his shoe to brush aside a couple of used needles littering the ground near a concrete arroyo in a seedy west side neighborhood. The 73-year-old lay chaplain said he used to work with drug addicts at this spot all the time. He'd park the white minivan paid for in part by St. Mark's Episcopal Church and throw open the trunk. Sickly and desperate and dying, they'd swarm him as he directed them to places to get help and gave them clean needles in an effort to keep them from spreading HIV and hepatitis C.
Now, the red-haired retiree, himself living with AIDS for the last decade, is awaiting word on whether he'll land in jail for a year for administering a program that has been legalized in every state in the nation but Texas.”[truncated]
Indian clinics uncover high rate of hepatitis C
“An epidemiological study conducted at two Indian Health Service clinics in Montana uncovered a hepatitis C infection rate that is six times higher than is found in the general population. The finding surprised tribal and state health officials, who responded by creating an educational brochure that targets young American Indians.” [truncated]
15 hepatitis infections tied to ex-nurse
“EL PASO, Texas- At least 15 military service members or their relatives are believed to have been infected with hepatitis by a nurse suspected of stealing their painkillers during surgery. The nurse, retired Army captain Jon Dale Jones, was arrested this month in Miami on federal charges of assaulting three of those patients and possession of a controlled substance by fraud.” [truncated]
XTL licenses hepatitis C program
“XTL Biopharmaceuticals Ltdhas licensed it pre-clinical program in hepatitis C focused on the NS5A target to Presidio Pharmaceuticals Inc. Presidio will take over all further development and commercialization activities and costs relating to the hepatitis C program. XTL will receive an upfront payment of $4 million, and up to an additional $104 million upon reaching certain development and commercialization milestones.” [truncated]
Inovio Biomedical reveals safety results of Tripep's ChronVac-C delivered using Inovio's Electroporation Delivery Systems
“Monday morning, biomedical company Inovio Biomedical Corp. said that its partner Tripep AB of Sweden reported preliminary results from its Phase I/II clinical study of therapeutic hepatitis C virus, or HCV, vaccine, ChronVac-C, which was delivered using Inovio's electroporation-based DNA delivery system.” [truncated]
Hepatitis C drug may offer potential treatment strategy for muscular dystrophy
“In a rodent study, researchers at Cincinnati Childrens Hospital Medical Centre have cited that an investigational antiviral drug, currently undergoing human trials in Europe for treating Hepatitis C infections, may act as a potential treatment strategy to reduce muscle cell damage in Duchenne and other forms of muscular dystrophy (MD). The drug, namely Debio-025, is a popular inhibitor of the protein cyclophilin D, regulates the swelling of mitochondria in response to cellular injury.” [truncated]
Valeant Pharmaceuticals reports encouraging phase IIb results at treatment week 12 for Taribavirin
“Valeant Pharmaceuticals today reported results at the treatment week 12 analysis point for the Phase IIb clinical trial for its antiviral compound, taribavirin, a prodrug of ribavirin in development for the treatment of chronic hepatitis C in conjunction with a pegylated interferon.” [truncated]
Contest seeks to break silence; poster design competition aims to raise hep C awareness [Canada]
“The way Ernie Zivny sees it, $4,000 is a miniscule amount to spend if it can prevent even a handful of people from contracting a deadly, blood-borne liver disease. "That's why there is a $500 first prize," explained the Greater Sudbury man, about the Circle C Support Group's "Break the Silence and Win" Contest. "If they are going to do their own research, we are going to get good involvement in finding out about hep C and by putting it in their entry - ‘how can I get it, how can I prevent it?’ They are going to keep that with them for the rest of their life." Zivny, who contracted hepatitis C through a tainted blood transfusion a 1978 operation and only learned he had the disease in 2001, is providing the $4,000 total prize money for the contest, which is open to all ages, but focuses on students.” [truncated]
Oncolys and Tacere partner in hepatitis C drug development
“Oncolys BioPharma and Tacere Therapeutics have entered into a strategic alliance and license agreement to develop and commercialize throughout Asia, Tacere's RNA interference-based hepatitis C virus compound, TT-033. This agreement resulted from the strategic alliance entered into by Tacere and Oncolys in June 2007, whereby Oncolys was granted an option to acquire the Asian rights for TT-033. Under the terms of the agreement, Oncolys and Tacere will form a joint steering committee that will work with the Tacere and Pfizer steering committee to oversee preclinical R&D efforts for TT-033 (code-named by Oncolys as OBP-701).” [truncated]
Blood donations down after Las Vegas hepatitis C scare
“Blood donations have dropped since a hepatitis scare triggered a massive health alert in southern Nevada. Officials say donations at the United Blood Services five fixed sites have dropped 25 percent since early March. That's when 40,000 former patients at the Endoscopy Center of Southern Nevada were told to be tested for potentially fatal viruses hepatitis B and C and HIV. The clinic was found to be practicing unsafe injection procedures.”
Hepatitis C may reduce EPO requirements
“Hemodialysis patients infected with hepatitis C virus (HCV) have a significantly decreased requirement for erythropoietin (EPO) compared with hemodialysis patients with no history of HCV infection, according to researchers. A team at Texas A & M University in Temple, led by Anand Khurana, MD, studied 66 hemodialysis patients: 22 with HCV infection and 44 age-, gender-, and race-matched controls without HCV. The mean EPO requirement for the HCV-infected group was 17,307 U/month compared with 49,134 U/month for controls, the investigators reported in Hemodialysis International (2008;12:94-99). The HCV-infected patients also tended to have higher hemoglobin levels at baseline.”[truncated]
DA raids office of Dix Hills doc in hep C probe
“The Nassau County district attorney's office raided Dr. Harvey Finkelstein's office yesterday as part of a probe into whether the Dix Hills physician caused two cases of hepatitis C and not one as state health authorities previously believed, according to court records, medical documents and interviews.
Investigators seized medical records and a computer hard drive from Finkelstein's Plainview medical office on Old Country Road yesterday morning. Prosecutors are considering whether they can bring felony charges. They could include second-degree assault, apparently for causing the infections, and falsifying business records and offering a false instrument, for changing or withholding records from the state Department of Health, according to an affidavit for the search warrant.” [truncated]
HIV-positive gay men being infected with HCV soon after HIV; cases of HCV superinfection reported
“Many gay men are being infected with hepatitis C virus soon after they contract HIV, according to a study conducted in London and published in the March 12th edition of AIDS. The study, conducted at St Mary's Hospital, found that 7% of gay men diagnosed with HIV at the hospital between 1999 and 2006 went on to become infected with hepatitis C virus through sex.” [truncated]
AANA condemns unsafe injection practices
“In a decisive response to recent incidents in Nevada and New York in which patients were infected with hepatitis C allegedly through the reuse of needles and syringes, the American Association of Nurse Anesthetists (AANA) today called on healthcare professionals across the nation to exercise the utmost care and vigilance when performing or observing injections on patients.” [truncated]
Egypt: Poor hygiene, ignorance blamed for prevalence of hepatitis C
HCV has a higher prevalence among older Egyptians, but is still spreading among the younger generation
“The results of an ongoing national survey on the prevalence of the hepatitis C virus (HCV) in Egypt, to be released later this year, will tell how much of a problem the disease still is in the country, said specialists. The survey is being conducted by the National Committee for the Control and Prevention of Viral Hepatitis, a government body formed last year to tackle the disease. A similar survey in 1996 showed that 10-12 percent of the population had HCV, with 70,000-140,000 new infections each year, according to Manal Hamdy al-Sayed, Professor of Paediatrics at Cairo's Ain Shams University and a member of the Committee. Al-Sayed was part of a team which formulated an action plan to fight the disease and combat rising mortality. Egypt has one of the highest HCV prevalence rates in the world. About one in every 10 persons has the virus, said al-Sayed.” [truncated]
Outreach offers hepatitis C test kits
“A local nonprofit organization is offering free kits to test for Hepatitis C. The Hepatitis C Multicultural Outreach in Kansas City is a asking for donations of about $10 for the kit. Anyone interested in picking up a kit can call 816-442-8089. Hepatitis C Multicultural Outreach is located at 10515 Blue Ridge Blvd. Suite 207 in Kansas City.”
In memory of an assemblyman, NY legislature creates hepatitis council
“There were some tears and some people got choked up as they spoke, but the goal was unwavering: fighting hepatitis C, what they called "a silent epidemic." In the wake of the death last year of state Assemblyman Kenneth Zebrowski, D-New City, Rockland County, to hepatitis C, state officials and lawmakers announced Wednesday the creation of a hepatitis C Advisory Council to improve prevention, detection and treatment of the disease. Gov. Eliot Spitzer put $1.6 million in his 2008-09 budget proposal to form the council and fund research and programs.” [truncated]
Hepatitis C investigation creating doctor shortage
“Health experts estimate the Hepatitis C scare is taking a toll on gastroenterologists in the Valley. Officials found staff at the Endoscopy Center of Southern Nevada reused syringes on patients, putting thousands of people who visited the Shadow Lane office at risk for various viruses. Before the health scare, there were about 46 GI doctors practicing in Southern Nevada. Now, there may only be about 18 practicing.” [truncated]
50 Riverside patients scheduled for hepatitis C screenings
“NEWPORT NEWS - Riverside nurses have scheduled about 50 appointments for hepatitis C screenings.The screenings are being offered to 310 patients who came in contact with a nurse anesthetist who worked there and is accused of infecting up to 15 patients with hepatitis C in Texas in 2004. Jon Dale Jones, 45, a retired Army captain, worked for an independent contractor at Riverside Regional Medical Center from July 9 to Dec. 22. There's no indication Riverside patients were exposed to the infection, but the health system is offering screenings for those 310 patients as a precaution, said Chris Stolle, vice president of medical affairs.” [truncated]
U.S. hepatitis C soars in those over 45
“U.S. mortality rates for hepatitis C in people ages 45 to 54 rose 375 percent from 1995 to 2004, researchers said. The findings, published in Hepatology, found hepatitis C rose in those ages 55 to 64 rose by 188 percent during the same period. "Substantial increases in overall hepatitis-C-related mortality rates have occurred since 1995," the study authors said in a statement. "The relatively young age of persons dying from hepatitis C-related liver disease has made hepatitis C-related disease a leading infectious cause of years of potential life lost as well as an important cause of premature mortality overall."” [truncated]
Vertex Pharmaceuticals announces acceptance of late-breaker abstract on Telaprevir, investigational HCV protease inhibitor, for presentation at EASL annual meeting
“Vertex Pharmaceuticals Incorporated today announced that data related to its investigational hepatitis C protease inhibitor telaprevir will be featured in a late-breaker poster presentation during the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL) in Milan, April 23-27, 2008.
The title of the abstract is "A Study of Telaprevir (TVR) with Peginterferon alfa-2A (P) and Ribavirin (R) in Subjects with Well-documented Prior P/R Null Response, Non-Response or Relapse: Preliminary Results" and will be presented at EASL starting on Thursday, April 24. Accepted late-breaker abstracts for the EASL meeting are now available on the EASL website. Information contained in the late-breaker poster abstract has also been filed by Vertex with the U.S. Securities and Exchange Commission on a Form 8-K.” [truncated]
Allman Brothers Band says Gregg Allman has hepatitis C; cancels several concerts
“An Allman Brothers Band member says Gregg Allman is unable to play several upcoming concerts because of his treatments for hepatitis C. Drummer Butch Trucks says the band has canceled appearances in Florida next month and bowed out of its annual run of shows at Manhattan's Beacon Theatre in May. Trucks says Allman began undergoing treatment last year. The Allman Brothers Band was founded in Florida in the late 1960s, but gained fame while living in Macon, Ga. The band was inducted into the Rock and Roll Hall of Fame in 1995.”
Government of Canada funds research to address hepatitis C virus in Central Alberta [Canada]
“MP Bob Mills, Member of Parliament for Red Deer, today announced on behalf of Health Minister Tony Clement, a $10,000 contribution to the Central Alberta AIDS Network Society (CAANS) to fund a project that aims to reduce the incidence of hepatitis C virus (HCV) in Central Alberta by assessing the health needs of those most at-risk of becoming infected. The project, entitled Street Smarts Outreach: Rural Needs Assessment in Central Alberta, will determine the health needs of drug users in the region and the capacity of rural communities to increase HCV awareness and prevention initiatives.” [truncated]
Doctors link ‘heroin days’ to hepatitis C
“ The heroin problem on Guam between the late 1970s and early 1980s still haunts some island families today. Needle-sharing associated with the use of heroin helped spread Hepatitis C on island, and complications of the disease have led to "the premature deaths of too many Guamanians," according to fliers that some Guam doctors are circulating to try to raise awareness of the problem. "If you shared a needle 30 or 40 years ago, you could be infected with a deadly disease and not even know it," according to the fliers, which are being circulated islandwide.” [truncated]
CLINICAL TRIALS, COHORT STUDIES, PILOT STUDIES
Association between hepatitis B/C viral infection, chronic kidney disease and insulin resistance in individuals undergoing general health screening. Ishizaka N, etal. Hepatol Res. 2008 Mar 25 [Epub ahead of print]
Racial differences in liver transplantation outcomes in the MELD era. Ananthakrishnan AN, Saeian K. Am J Gastroenterol. 2008 Mar 26 [Epub ahead of print]
Scientific rationale and study design of the individualized dosing efficacy vs flat dosing to assess optimal pegylated interferon therapy (IDEAL) trial: determining optimal dosing in patients with genotype 1 chronic hepatitis C. McHutchison J, Sulkowski M. J Viral Hepat. 2008 Mar 24 [Epub ahead of print]
Hepatitis B virus DNA in liver tissue and risk for hepatocarcinogenesis in patients with hepatitis C virus-related chronic liver disease. A prospective study. Obika M, et al. Intervirology. 2008 Mar 18;51(1):59-68 [Epub ahead of print]
The efficacy of short-term interferon-beta therapy for chronic hepatitis C patients with low virus load. Kawamura Y, et al. Intern Med. 2008;47(5):355-60. Epub 2008 Mar 3
Prevalence of diabetes mellitus and insulin resistance in patients with chronic hepatitis C: comparison with hepatitis B virus-infected and hepatitis C virus-cleared patients. Imazeki F, et al. Liver Int. 2008 Mar;28(3):355-62.
Clinical significance of elevated alpha-fetoprotein in Alaskan Native patients with chronic hepatitis C. Bruce MG, et al. J Viral Hepat. 2008 Mar;15(3):179-87
Pathology of chronic hepatitis C in children: liver biopsy findings in the Peds-C Trial. Hepatology. 2008 Mar;47(3):836-43.Goodman ZD, et al.
BASIC AND APPLIED SCIENCE, PRE-CLINICAL STUDIES
Steatosis correlates with hepatic expression of death receptors and activation of nuclear factor-kappaB in chronic hepatitis C.
Hung CH, et al. Liver Int. 2008 Mar;28(3):339-46.
Relationship of serum fibrosis markers with liver fibrosis stage and collagen content in patients with advanced chronic hepatitis C.
Fontana RJ, Hepatology. 2008 Mar;47(3):789-98.
Interferon and ribavirin therapy does not select for resistance mutations in hepatitis C virus polymerase. Ward CL, et al. J Viral Hepat. 2008 Mar 24 [Epub ahead of print]
Toll-like receptor-stimulated non-parenchymal liver cells can regulate hepatitis C virus replication. Broering R, et al. J Hepatol. 2008 Mar 3 [Epub ahead of print]
Essential role of domain III of nonstructural protein 5A for hepatitis C virus infectious particle assembly. Appel N, et al. . PLoS Pathog. 2008 Mar 28;4(3):e1000035.
Altered natural killer cell subset distributions in resolved and persistent hepatitis C virus infection following single source exposure. Golden-Mason L, et al. Gut. 2008 Mar 27 [Epub ahead of print]
A critical role of virion-associated cholesterol and sphingolipid in hepatitis C virus infection. Aizaki H, et al. J Virol. 2008 Mar 26 [Epub ahead of print]
Expansion of hepatitis C-specific CD4(+)CD25(+) regulatory T cells after viral clearance: A mechanism to limit collateral damage? Godkin A, et al. J Allergy Clin Immunol. 2008 Mar 18 [Epub ahead of print]
Existence of hepatitis C virus NS5B variants naturally resistant to non-nucleoside, but not to nucleoside, polymerase inhibitors among untreated patients. Le Pogam S, et al. J Antimicrob Chemother. 2008 Mar 20 [Epub ahead of print]
Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C. Fujita N, et al. J Viral Hepat. 2008 Mar 6 [Epub ahead of print]
Cutting edge: programmed death-1 expression is increased on immunocytes in chronic hepatitis C virus and predicts failure of response to antiviral therapy: race-dependent differences. Golden-Mason L, et al. J Immunol. 2008 Mar 15;180(6):3637-41.
Iminosugars in combination with interferon and ribavirin permanently eradicate non-cytopathic bovine viral diarrhoea virus from persistently infected cells. Woodhouse SD, et al. Antimicrob Agents Chemother. 2008 Mar 3 [Epub ahead of print]
HCV infection in haemodialysed patients: A role for serum IL-10 and TGF-beta(1) in liver damage? Burra P, et al. Dig Liver Dis. 2008 Mar 25 [Epub ahead of print]
HCV selection and HVR1 evolution in a chimpanzee chronically infected with HCV-1 over 12 years. Lu L, et al. Hepatol Res. 2008 Mar 4 [Epub ahead of print]
Genetic variability in hepatitis C virus and its role in antiviral treatment response. Torres-Puente M, et al. J Viral Hepat. 2008 Mar;15(3):188-99.
Association of HIV infection and HIV/HCV coinfection with C-reactive protein levels: the fat redistribution and metabolic change in HIV infection (FRAM) study. Reingold JS, et al. J Acquir Immune Defic Syndr. 2008 Mar 13 [Epub ahead of print]
The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. Flisiak R, et al. Hepatology. 2008 Mar;47(3):817-26.
Progression of fibrosis in HIV and hepatitis C virus-coinfected patients treated with interferon plus ribavirin-based therapy: analysis of risk factors. Bani-Sadr F, et al. Clin Infect Dis. 2008 Mar 1;46(5):768-74.
COMPLEMENTARY & ALTERNATIVE THERAPY
Acetyl-L: -Carnitine treatment in minimal hepatic encephalopathy. Malaguarnera M, et al. Dig Dis Sci. 2008 Mar 21 [Epub ahead of print]
Suppressive effect of oral administration of branched-chain amino acid granules on oxidative stress and inflammation in HCV-positive patients with liver cirrhosis. Ohno T, et al. . Hepatol Res. 2008 Mar 4 [Epub ahead of print]
Eicosapentaenoic acid supplementation for chronic hepatitis C patients during combination therapy of pegylated interferon alpha-2b and ribavirin. Kawashima A, et al. Lipids. 2008 Mar 5 [Epub ahead of print]
Circulating beliefs, resilient metaphors and faith in biomedicine: hepatitis C patients and interferon combination therapy.
Jenner A, Scott A. Sociol Health Illn. 2008 Mar;30(2):197-216.
All-trans retinoic acid for treatment of chronic hepatitis C. Böcher WO, et al. Liver Int. 2008 Mar;28(3):347-54.
EPIDEMIOLOGY, DIAGNOSTICS, AND MISCELLANEOUS WORKS
Screening for hepatitis C in sexual health clinic attendees. Mapagu MC, et al. Sex Health. 2008 Mar;5(1):73-6.
Occult hepatitis C virus infection during an outbreak in a hemodialysis unit in Thailand. Thongsawat S, J Med Virol. 2008 Mar 21;80(5):808-815 [Epub ahead of print]
Pain, substance use disorders and opioid analgesic prescription patterns in veterans with hepatitis C. Whitehead AJ, et al. J Pain Symptom Manage. 2008 Mar 19 [Epub ahead of print]
Prevalence and determinants of hepatitis C virus infection among female drug injecting sex workers in Glasgow. Taylor A, et al. Harm Reduct J. 2008 Mar 20;5(1):11 [Epub ahead of print]
Surveillance for acute viral hepatitis--United States, 2006. Wasley A, Grytdal S, Gallagher K. MMWR Surveill Summ. 2008 Mar 21;57(2):1-24.
Gastroenterologists' perceptions of need and availability of psychiatric services for patients with hepatitis C. Gleason O, Fucci J, Yates W. Psychosomatics. 2008 Mar-Apr;49(2):132-6
Quality-of-life tradeoffs for hepatitis C treatment: do patients and providers agree? Schackman BR, et al. Med Decis Making. 2008 Mar-Apr;28(2):233-42. Epub 2008 Mar 18.
Identified cases of acute hepatitis C from computerized laboratory database: A hospital-based epidemiological and clinical study. Hung CH, et al. J Infect. 2008 Mar 15 [Epub ahead of print]
Hepatitis C virus reinfection in liver transplant patients: Evaluation of liver damage progression with echo-color doppler.
Bolognesi M, et al. Liver Transpl. 2008 Mar 6 [Epub ahead of print]
Can urban methadone patients complete health utility assessments? Teixeira PA, Schackman BR. Patient Educ Couns. 2008 Mar 1 [Epub ahead of print]
Impact of chronic liver disease and cirrhosis on health utilities using SF-6D and the health utility index. Dan AA, et al. Liver Transpl. 2008 Mar;14(3):321-6.
Outcome of an exercise to notify patients treated by a general surgeon infected with the hepatitis C virus. Ross RS, et al. J Clin Virol. 2008 Apr;41(4):314-7. Epub 2008 Mar 4.
Hepatitis C testing and infection rates in bipolar patients with and without comorbid substance use disorders. Matthews AM, et al. Bipolar Disord. 2008 Mar;10(2):266-70.
The effect of early virological response in health-related quality of life in HCV-infected patients. Quarantini LC, et al. J Med Virol. 2008 Mar;80(3):419-23.
Optical analysis of computed tomography images of the liver predicts fibrosis stage and distribution in chronic hepatitis C.
Romero-Gómez M, et al. Hepatology. 2008 Mar;47(3):810-6.
Diagnostic Accuracy of Serum Hyaluronic Acid, FIBROSpect II, and YKL-40 for Discriminating Fibrosis Stages in Chronic Hepatitis C. Mehta P, et al. Am J Gastroenterol. 2008 Mar 25 [Epub ahead of print]
Rapid viral response and treatment outcome in genotype 2 and 3 chronic hepatitis C: comparison between two HCV RNA quantitation methods.
Carlsson T, Quist A, Weiland O. J Med Virol. 2008 Mar 21;80(5):803-807 [Epub ahead of print]
(13)C-methacetin-breath test compared to also noninvasive biochemical blood tests in predicting hepatic fibrosis and cirrhosis in chronic hepatitis C. Dinesen L, et al. Dig Liver Dis. 2008 Mar 11 [Epub ahead of print]