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Newborn screening for urinary cytomegalovirus (CMV) and early introduction of antiviral treatment are expected to improve neurological outcomes in symptomatic congenital CMV-infected infants. This cohort study prospectively evaluated neurological outcomes in symptomatic congenital CMV-infected infants following the introduction of hospital-based newborn urinary CMV screening and antiviral treatment.
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Abdominal pain is a common symptom after bone marrow transplant; however, typhlitis is relatively rare, and surgical intervention was not required in this series. Broad-spectrum (including fungal) antibiotic therapy appears to be an effective treatment for typhlitis in this patient population.
A multicenter, randomized, double-masked study.
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Acyclovir protects against aspirin-induced attacks of asthma through mechanisms unrelated to its bronchodilator property but related to the improvement of bronchial hypersensitivity to sulpyrine; protection was nearly complete in all patients (P <.0001). By contrast, after acyclovir, the maximum level of u-LTE4 in patients was significantly lower than that in control subjects (P <. 01).
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Herpes simplex virus is one of the most common causes of genital ulcer disease worldwide. Herpes simplex virus-2 is the more common cause of genital herpes, a chronic infection that is characterised by periodic reactivation, with the capacity to produce recurrent symptomatic disease in the host (e.g., vesicular eruption), as well as intermittent asymptomatic shedding. Relapsing episodes may be physically and psychologically distressing. Shedding accounts for the majority of cases of transmission of genital herpes to sexual partners. Pregnant women who are shedding may transmit the virus at the time of delivery, with severe and potentially fatal consequences to the baby. Famciclovir, a synthetic acyclic guanine derivative, is the prodrug of penciclovir, which demonstrates in vitro antiviral activity against various types of herpes virus, including herpes simplex virus-2. Its pharmacokinetics allow for administration in a convenient dosing regimen compared with acyclovir, which may improve compliance. Clinical studies have demonstrated its efficacy in the episodic treatment of relapses, with the most recent report demonstrating its efficacy and tolerance as a single-day treatment. It is also efficacious and well tolerated for the suppression of frequently recurring episodes. These results have been demonstrated in various patient populations, including immunocompetent patients and those infected with HIV. Famciclovir is well tolerated, with an adverse events profile similar to placebo.
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Diabetic patients undergoing simultaneous kidney-pancreas transplantation (SKPT) may be at high risk for developing cytomegalovirus (CMV) infection. To study this issue, we analyzed 297 SKPT patients enrolled into a multicenter trial of two daclizumab dosing strategies versus no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids. Complete donor (D) and recipient (R) CMV serology values were available in 294 cases and were distributed as follows: 86 (29%) D+/R-. Eighty-six (29%) D+R+; 45 (16%) D-/R+; 77 (26%) D-/R-; CMV antiviral prophylaxis was center specific, but 98% of patients received either ganciclovir or acyclovir. No differences existed in demographic or transplant characteristics or immunosuppressive regimens among the four groups except that more African-American SKPT recipients were CMV positive at transplant (P <.001). At 6 months, no differences were seen in patient and graft survival rates (GSR) and the incidence of acute rejection (AR) among the groups. However, the CMV D+/R- group had a significantly higher incidence of CMV infection/disease (14%) than the other groups collectively (4%, P <.05). Most cases of CMV infection/disease occurred greater than 3 months posttransplant when prophylaxis was discontinued. In the D-/R- group, the pancreas GSR was higher (94% vs 86% in the remaining three groups) and the incidence of AR was lower (16% vs 25% in the remaining three groups, both P =.09). Primary CMV exposure remains a major risk factor for CMV infection/disease, but does not have an adverse impact on short-term outcomes. Conversely, protective CMV seronegative matching may have a beneficial effect on outcomes.
To observe the effects of bloodletting pricking, cupping and surrounding acupuncture on blood inflammation-related indices in patients with acute herpes zoster (HZ), and to explore the mechanism of pain control and treatment.
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RLU was significantly higher in PEI group than in DOTAP and naked DNA groups (187.35+/-6.48 vs. 45.74+/-5.98, and 0.03+/-0.00,P<0.01). Evident GCV cytotoxicity was observed in SKOV3 cells, but negligible in SMMC7721 cells. The concentration of GCV in SKOV3 cells was gradually decreased with treatment prolonging. FCM showed that the apoptotic rate of pOSP1-HSVtk-transfected SKOV3 cells was increased when exposed to GCV for 24, 48, and 72 h [(8.42+/-0.76)%, (18.50+/-1.78)%, (34.80+/-3.46)%]. A lot of apoptotic SKOV3 cells were detected by TUNEL.
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The cyclosaligenyl (cycloSal) derivatives of the monophosphates of three acyclic or carbocyclic guanosine analogues, for example, acyclovir (ACV), carbovir (CBV) and abacavir (ABC), were investigated for their activity against retrovirus (HIV, Moloney sarcoma virus) and herpes simplex virus (HSV) activity in cell culture. The extent of the antiviral potency of the prodrugs depended on the nature of the nucleoside, the substituent on the cycloSal moiety and the virus investigated. Most notably, and unlike the parent compound ACV, cycloSal-ACV monophosphate (MP) prodrugs retained pronounced activity against ACV-resistant (thymidine kinase-deficient) HSV-1 and also gained anti-HIV activity. While the cycloSal-CBVMP prodrugs did not show enhanced activity compared with the parent compound CBV, the cycloSal-ABCMP prodrugs afforded markedly increased potency against both HSV and HIV. Our data indicate that the cycloSal prodrug approach can be useful to deliver directly the MP derivatives of nucleoside analogues into the intact, virus-infected cells, thus improving and extending the antiviral potency and spectrum of the drugs against retro- and herpesvirus strains.
In this randomized, double-blind, multicenter, acyclovir-controlled study, the efficacy and safety of famciclovir were evaluated for the treatment of herpes zoster in patients who were immunocompromised following bone marrow or solid organ transplantation or oncology treatment. A total of 148 patients, 12 years or older with clinical evidence of localized herpes zoster, received either oral famciclovir, 500 mg three times daily, or acyclovir, 800 mg five times daily, for 10 days. Famciclovir was equivalent to acyclovir with respect to the numbers of patients reporting new lesion formation while on therapy (77% vs. 73%, respectively). There were no significant differences between the groups in the time to cessation of new lesion formation, full crusting, complete healing of lesions, or loss of acute phase pain. Treatment with famciclovir was well tolerated, with a safety profile comparable to that of acyclovir. Thus oral famciclovir is a convenient, effective, and well-tolerated regimen for immunocompromised patients with herpes zoster.
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Vitreous GCV levels at days 21 and 42 were similar in both the saline-filled and silicone oil-filled eyes. At day 70, GCV levels in both the saline- and silicone-filled eyes were statistically significantly lower than at day 21 (P < 0.05 for all groups). In addition, at day 70, GCV levels in the saline-filled eyes were significantly lower than in silicone-filled eyes (saline versus 0.5 cc oil, P = 0.01; saline versus 1 cc oil, P = 0.09).
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We describe the case of a 16-month-old girl with neuroblastoma and chronic lymphocytopenia due to chemotherapy and treosulfan-containing megatherapy who developed cytomegalovirus retinitis and neuritis. Intravenous ganciclovir and anti-cytomegalovirus immunoglobulin were used with a transient benefit; however, retrobulbar gancyclovir resulted in a complete remission. This report emphasizes the need for close monitoring of viral infections in patients undergoing treosulfan-containing megatherapy, highlighting the immunosuppressive effects of this agent, and indicates the potential use of retrobulbar ganciclovir as the alternative method of drug delivery.
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Valaciclovir (VAL) is the L-valyl ester of acyclovir and it is quickly hydrolysed to acyclovir. Acyclovir-related nephrotoxicity is associated with high drug infusion doses and VAL-related neurotoxicity to pre-existing renal failure. We observed two geriatric patients with normal serum creatinine who developed acute renal failure (ARF) and neurotoxicity after ingesting the drug at the conventional therapeutic dose.
This paper describes a stripping method for the determination of nevirapine at the submicromolar concentration levels. The method is based on controlled adsorptive accumulation of nevirapine at thin-film mercury electrode, followed by a linear cyclic scan voltammetry measurement of the surface species. Optimal experimental conditions include a 2.0 x 10(-3) mol L(-1) NaOH solution (supporting electrolyte), an accumulation potential of -0.20 V, and a scan rate of 100 mV s(-1). The response of nevirapine is linear over the concentration range 0.01-0.14 ppm. For an accumulation time of 6 minutes, the detection limit was found to be 0.87 ppb (3.0 x 10(-9) mol L(-1)). More convenient methods to measure the nevirapine in presence of the efavirenz, acyclovir, didanosine, indinavir, nelfinavir, saquinavir, lamivudine, zidovudine and metals ions were also investigated. The utility of this method is demonstrated by the presence of nevirapine together with ATP or DNA.
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Patients (n=239) enrolled in a study of intravenous ganciclovir or valganciclovir for the treatment of HCMV disease were analysed by a gB genotype specific PCR to quantify the amount of each gB genotype present at initiation of therapy (baseline, day 0) and at days 3, 7, 14 and 21 post therapy.
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Among the patients who were all D(+)/R(+) (CMV-Immunoglobulin G [IgG](+)/IgG(+)). 10 required treatment (18%) within 3 months from OLT. There subjects were prescribed TRL (n = 4) or CsA (n = 6). No renal impairment was observed among treated patients. Of those having the infection, one died due to other causes-sepsis from candida at 5 months after OLT.
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The purpose of this guideline is to provide recommendations to gynaecology health care providers on optimal management of genital herpes.
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The efficacy of the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) suicide-gene therapy system on human hepatocellular carcinoma was observed in vitro as well as ex vivo.
Options are available to manage HZ and reduce the pain of PHN. However, prevention, now possible with the HZ vaccine, is preferable to treatment.
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In the era of high-dose chemotherapy and novel antimyeloma agents, the survival of multiple myeloma (MM) patients has substantially improved. Adverse effects, including infections, may however arise in the era of combination antimyeloma therapies. In general, MM patients have shown a risk of varicella zoster virus (VZV) infection of 1-4 %, increasing with bortezomib treatment or transplants, but whether immunomodulatory drugs also bear a risk of VZV/complicated herpes simplex virus (HSV) (e.g., VZV-encephalitis [VZV-E], disseminated VZV-infection [d-VZV-i], or conus-cauda syndrome [CCS]) has not been elucidated. We here assessed VZV, VZV-E, d-VZV-i, and CCS in 93 lenalidomide-treated MM patients, consecutively seen and treated in our department. Patients' data were analyzed via electronic medical record retrieval within our research data warehouse as described previously. Of the 93 MM patients receiving lenalidomide, 10 showed VZV or other complicated VZV/HSV infections. These VZV patients showed defined risk factors as meticulously assessed, including suppressed lymphocyte subsets, substantial cell-mediated immune defects, and compromised humoral immune response. Due to our findings-and in line with an aciclovir prophylaxis in bortezomib and stem cell transplant protocols-we introduced a routine aciclovir prophylaxis in our lenalidomide protocols in May 2012 to minimize adverse events and to avoid discontinuation of lenalidomide treatment. Since then, we have observed no case of VZV/complicated HSV infection. Based on our data, we encourage other centers to also focus on these observations, assess viral infections, and-in those centers facilitating a research data warehouse-advocate an analogue data review as an appropriate multicenter approach.
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hTERT silencing by shRNA induced the expression of BZLF1, EA-D, and gp350 EBV lytic proteins and triggered a complete lytic cycle. This effect was associated with downregulation of BATF, a negative regulator of BZLF1 transcription. hTERT silencing also resulted in antiproliferative and proapoptotic effects. In particular, hTERT inhibition induced an accumulation of cells in the S-phase, an effect likely due to the dephosphorylation of 4E-BP1, an AKT1-dependent substrate, which results in a decreased availability of proteins needed for cell-cycle progression. Besides inducing cell death through activation of complete EBV lytic replication, hTERT inhibition triggered AKT1/FOXO3/NOXA-dependent apoptosis in EBV-positive and -negative Burkitt's lymphoma cells. Finally, ganciclovir enhanced the apoptotic effect induced by hTERT inhibition in EBV-positive Burkitt's lymphomas and LCLs.
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Human cytomegalovirus (HCMV) is a common opportunistic infection resulting in retinitis in 15%-40% of AIDS patients. Several anti-HCMV therapies are currently available, and new treatments are in various stages of development. An HCMV animal model involving in vivo infection of human cells without the dependence on human fetuses or multiple surgical procedures has been developed. A human glioblastoma cell line that is permissive for HCMV replication (U373MG) was adapted to grow as a subcutaneous tumor in nude mice. These tumors arise in approximately 7 days and grow progressively. An evaluation of HCMV DNA replication demonstrated an increase in the accumulation of HCMV DNA within infected tumors from 48 to 168 h after infection. Immunohistochemical analysis showed focal areas of HCMV infection in which expression of immediate-early and late antigens was detected. In addition, it was demonstrated that ganciclovir inhibited HCMV DNA replication in vivo in a dose-dependent manner.
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Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis. It has been shown that promoter sequences of the TSP-1 gene can be transactivated by the wild-type tumor suppressor protein p53. As human cytomegalovirus (HCMV) infection inactivates wild-type p53 of various cell types, we investigated whether HCMV infection is associated with reduced TSP-1 production. We found, in conjunction with accumulated p53, that TSP-1 mRNA and protein expression was significantly reduced in HCMV-infected cultured human fibroblasts. To determine whether the observed TSP-1 suppression depends on p53 inactivation, the p53-defective astrocytoma cell line U373MG was infected with HCMV. In these cells TSP-1 expression was also significantly reduced by HCMV infection whereas expression of the p53 mutant variant remained unaltered. In both cell lines the decreased expression of TSP-1 mRNA occurred early after infection (4 hours), indicating that HCMV inhibits TSP-1 transcription during the immediate-early phase of infection before HCMV DNA replication. Inhibition of HCMV DNA synthesis by ganciclovir did not influence TSP-1 reduction whereas the antisense oligonucleotide ISIS 2922, complementary to HCMV immediate-early mRNA, completely prevented the HCMV-mediated TSP-1 suppression. These findings strongly suggest a novel role for HCMV in the modulation of angiogenesis due to p53-independent down-regulation of TSP-1 expression.
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Varicella-zoster virus (VZV), a member of the herpesvirus family, is responsible for both primary (varicella or chickenpox) as well as recurrent (zoster or shingles) infections. Acyclovir has been the mainstay for treating VZV infections in both immunocompetent and immunocompromised patients. Recently, newer anti-VZV drugs, i.e., valaciclovir (the oral prodrug form of acyclovir) and famciclovir (the oral prodrug form of penciclovir) have been developed and have enlarged the therapeutic options to treat VZV infections. Both acyclovir and penciclovir are dependent on the virus-encoded thymidine kinase (TK) for their intracellular activation. Although emergence of drug-resistant strains does not occur in immunocompetent patients, several reports have documented the isolation of drug-resistant VZV strains following long-term acyclovir therapy in immunocompromised patients. Mutations at the level of the TK are responsible for development of resistance to drugs that depend on the viral TK for their phosphorylation (i.e., acyclovir and penciclovir). Foscarnet, a direct inhibitor of the viral DNA polymerase, which does not require activation by the viral TK, is the drug of choice for the treatment of TK-deficient VZV mutants emerging under acyclovir therapy. Recently, emergence of foscarnet-resistant strains has also been reported. Both TK-deficient strains and foscarnet-resistant mutants are sensitive to the acyclic nucleoside phosphonate cidofovir, CDV, HPMPC, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine. This agent does not depend on the virus-encoded TK, but on cellular enzymes for its conversion to the diphosphoryl derivative, which then inhibits the viral DNA polymerase.