Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation.
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Retrospective analysis of 303 patients who underwent allogeneic hematopoietic stem cell transplantation identified 35 (11.5%) with adenovirus infection. Among them, 22 received specific therapy. As first-line therapy, 18 were treated with intravenous ribavirin, 3 with cidofovir, and 1 with vidarabine. Moreover, 2 received donor leukocyte infusion in combination with ribavirin, and 1 received it after failing to respond to other therapies. Seven survived (31.8%; 3 of 13 who received ribavirin alone and 2 of 3 who received cidofovir). Among the 5 patients treated with combined strategies, 2 who received donor leukocyte infusions showed clearance of all symptoms. Acute graft-versus-host disease grade > or = 3 (P = .01) and a long delay between infection and treatment (P = .05) correlated with a greater risk of treatment failure. In conclusion, ribavirin and vidarabine are ineffective options, particularly for patients at who are high risk of acquiring disseminated adenovirus disease. Conversely, cidofovir or donor leukocyte infusions seem to be encouraging approaches if initiated early. (+info)
Synthesis and anti-influenza virus activity of tricyclic compounds with a unique amine moiety.
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Several novel tricyclic compounds with a unique amine moiety (1, 2a--i) were designed and prepared based on the structure of triperiden for the development of anti-influenza virus agents. An in vitro antiviral assay showed that 1-(1-azabicyclo[3.3.0]octan-5-yl)-1-(4-fluorophenyl)-1-(2-tricyclo[3.3.1.1(3.7)]d ecyl)methan-1-ol hydrochloride (2f) has a potent anti-influenza A virus activity. Furthermore, since 2f was well tolerated in mice, 2f is promising as a novel anti-influenza virus agent for humans. (+info)
The effect of ribavirin to treat previously healthy infants admitted with acute bronchiolitis on acute and chronic respiratory morbidity.
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The role of ribavirin in the treatment of acute bronchiolitis is controversial. It has been suggested that the use of ribavirin may be of benefit during the acute illness and may reduce subsequent recurrent respiratory morbidity. This randomized, double-blind, placebo-controlled study was designed to determine whether ribavirin administered during the acute illness would have an influence on respiratory morbidity during both the acute illness and during the following year. Bronchial reactivity 6 months after the acute illness was also assessed. Forty previously well infants with moderately severe acute bronchiolitis were recruited during three winter epidemics. Subjects received study medication for 18 h a day. Management was otherwise unaltered. Subjects were evaluated daily by the investigator and subsequently assessed at 6 weeks, 6 months and 1 year following the acute illness. Assessment of bronchial hyper-responsiveness was assessed at 6 months of age using total body plethysmography and an established ultra-sonically nebulized distilled water challenge. A total of 40 patients (21 ribavirin, 19 placebo) were entered into the study. The two groups did not differ with respect to age, gender or clinical severity on entry to the trial. No significant differences were identified in the rate of clinical improvement over the first 24 h, the time to discharge, bronchial responsiveness at 6 months of age, frequency of significant respiratory symptoms over the first year of life and the frequency of prescribed bronchodilators and inhaled steroids during the year of follow-up. This study was unable to demonstrate any clinical benefit from the use of ribavirin in the acute illness or during subsequent follow-up for 1 year. (+info)
Dengue virus infects human endothelial cells and induces IL-6 and IL-8 production.
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In this study dengue virus (DV) was found to infect primary endothelial cells derived from human umbilical cord veins (HUVEC) and alter their cytokine production. Dengue virus infection of HUVEC was confirmed by an increase in plaque-forming units in the culture supernatant and by immunofluorescence assay. HUVEC produced large amounts of interleukin (IL)-6 and IL-8 but not IL-1beta after DV infection. Both the replication of DV and the production of IL-6 and IL-8 by HUVEC after DV infection were inhibited by ribavirin, an antiviral synthetic guanosine analogue. Additionally, increased serum levels of IL-6 and IL-8 were observed in patients with dengue hemorrhagic fever but not dengue fever. Therefore, our results suggest that endothelial cells can be a target for DV infection, and that DV-induced IL-6 and IL-8 production by endothelial cells may contribute to the pathogenesis of dengue hemorrhagic fever. (+info)
RNA virus error catastrophe: direct molecular test by using ribavirin.
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RNA viruses evolve rapidly. One source of this ability to rapidly change is the apparently high mutation frequency in RNA virus populations. A high mutation frequency is a central tenet of the quasispecies theory. A corollary of the quasispecies theory postulates that, given their high mutation frequency, animal RNA viruses may be susceptible to error catastrophe, where they undergo a sharp drop in viability after a modest increase in mutation frequency. We recently showed that the important broad-spectrum antiviral drug ribavirin (currently used to treat hepatitis C virus infections, among others) is an RNA virus mutagen, and we proposed that ribavirin's antiviral effect is by forcing RNA viruses into error catastrophe. However, a direct demonstration of error catastrophe has not been made for ribavirin or any RNA virus mutagen. Here we describe a direct demonstration of error catastrophe by using ribavirin as the mutagen and poliovirus as a model RNA virus. We demonstrate that ribavirin's antiviral activity is exerted directly through lethal mutagenesis of the viral genetic material. A 99.3% loss in viral genome infectivity is observed after a single round of virus infection in ribavirin concentrations sufficient to cause a 9.7-fold increase in mutagenesis. Compiling data on both the mutation levels and the specific infectivities of poliovirus genomes produced in the presence of ribavirin, we have constructed a graph of error catastrophe showing that normal poliovirus indeed exists at the edge of viability. These data suggest that RNA virus mutagens may represent a promising new class of antiviral drugs. (+info)
Hepatitis C: a brief clinical overview.
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Hepatitis C has emerged as an important public health problem that has affected 3.9 million Americans and 170 million people worldwide and is currently the most common indication for orthotopic liver transplantation. The disease, characterized by asymptomatic onset, is often discovered incidentally through blood tests obtained during routine physical examination or before blood donation. Spontaneous recovery occurs in about 20% of patients. Among those who remain chronically infected, an equal percentage progress to cirrhosis within 20 yr, have stable nonprogressive disease, or progress more slowly over 40 to 60 yr. At present, combination therapy with interferon plus ribavirin is the treatment of choice for hepatitis C-infected patients identified as appropriate candidates for therapy. Unfortunately, sustained response rates are only modest, with a lesser response among African Americans, and treatment is associated with a number of side effects. Research studies attempting to improve the response to current therapy, to identify alternative treatments or treatment strategies, and to develop an effective vaccine are ongoing and will hopefully provide us with the ability to better understand and manage hepatitis C. (+info)
High-dose prolonged combination therapy in non-responders to interferon monotherapy for chronic hepatitis C.
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BACKGROUND: Therapy of chronic hepatitis C non- responders to interferon monotherapy with standard doses of interferon plus ribavirin is usually ineffective. AIM: To evaluate the efficacy and tolerability of high-dose prolonged combination retreatment in non- responder patients. METHODS: Patients were retreated for 6 months with 6 MU alphaIFN on alternate days and 1000 or 1200 mg/day ribavirin. HCV-RNA negative patients continued therapy for an additional 6 months. RESULTS: Forty patients (29 males, mean age 49.7 years, 34 genotype 1b, 11 with F3 fibrosis) were treated. At 6 months, 20 (50%) patients were HCV-RNA negative but six of them discontinued therapy because of adverse events. A sustained response was achieved in 28% of patients (11/40). A sustained response was more frequent among patients with genotype non-1b than in those with genotype 1b (67 vs. 21%, P=0.005) and clearance of HCV-RNA in the first 3 months had a high predictive value for sustained response (100% of sustained responders vs. 24% of non-responders, P=0.0001). CONCLUSIONS: High-dose prolonged combination therapy in non-responders to IFN monotherapy leads to a higher rate of sustained response than the standard combination regimen. Tolerability may be a rate-limiting factor. Maximal effectiveness can be predicted in patients with non-1b genotype and in those who clear HCV-RNA soon after starting retreatment. (+info)
Respiratory syncytial virus infection in the late bone marrow transplant period: report of three cases and review.
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Respiratory syncytial virus (RSV) infection is an important cause of respiratory mortality in immunosuppressed patients, including bone marrow transplant (BMT) recipients. The presence of lower respiratory tract infection and infection in the pre-engraftment phase of BMT is believed to confer a poor prognosis. Three patients who underwent allogeneic BMT at our institution developed RSV pneumonia over 1 year post BMT, with the underlying disease in remission. All three were hypoxic with extensive pulmonary disease at presentation. Treatment consisted of aerosolized ribavirin and intravenous immune globulin with successful clearing of viral shedding and excellent clinical outcomes. RSV infection is probably less severe in the late post-BMT period, but needs to be considered early in the differential diagnosis of pulmonary infiltrates in this patient population. (+info)