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At least 253 records · Page 14Linked to original sources
PubMed2006

Strategies in the management of alemtuzumab-related side effects.

B-cell chronic lymphocytic leukemia has traditionally been treated with alkylating agents and purine analogues. The introduction of alemtuzumab, a CD52 monoclonal antibody with significant clinical activity in chemotherapy refractory B-cell chronic lymphocytic leukemia, is accompanied by a side effect profile different from that resulting from chemotherapy. The intravenous administration of alemtuzumab is usually accompanied by transient infusion-related side effects manifesting primarily as flu-like symptoms. These reactions can be reduced by use of corticosteroid prophylaxis, and will subside gradually during continued treatment. Alternatively, administration of alemtuzumab subcutaneously may markedly reduce the occurrence of general side effects but results in limited transient local skin reactions in most patients. Neutropenia (grade 4) may occur in approximately 20% of patients, but is usually transient and/or responds promptly to colony stimulating factor therapy; episodes of febrile neutropenia are infrequent. The major side effect of alemtuzumab is T-cell depletion, leading to an increased risk of infection, in particular reactivation of cytomegalovirus. This event typically occurs 3 to 8 weeks after initiation of therapy, coinciding with the T-cell nadir. With vigilance and early detection, these infections are usually manageable and do not cause organ failure. Preliminary data indicate that other infections following alemtuzumab therapy do not seem to occur at a frequency that is higher than expected, probably because of the general prophylactic use of cotrimoxazole (trimethoprim and sulfamethoxazole) and valacyclovir in combination with clinical tumor regressions. The overall safety profile of alemtuzumab appears to be beneficial in relation to disease severity and prognosis in patients with fludarabine-refractory B-cell chronic lymphocytic leukemia.

Alemtuzumab↗
PubMed2000

Antimicrobial prophylaxis in dermatology.

Few circumstances in dermatology warrant antimicrobial prophylaxis. In cutaneous surgery postoperative infections are too infrequent and insufficiently severe to justify preventive antibiotics, except rarely. Petrolatum is as effective as, and cheaper than, topical antibiotic ointment to cover surgical wounds. In patients with numerous staphylococcal skin infections, oral clindamycin 150 mg every day for 3 months safely reduces further episodes. For recurrent cellulitis, oral penicillin or erythromycin 250 mg twice daily or monthly intramuscular benzathine penicillin decreases subsequent attacks. In patients with frequent episodes of genital or labial herpes simplex an antiviral agent such as valacyclovir 500 mg to 1 g every day is effective as a suppressant.

Anti-Bacterial Agents↗
PubMed2002

Clinical manifestations and treatment considerations of herpes simplex virus infection.

Herpes simplex viruses (HSV) types 1 and 2 cause infections manifesting as dermatologic, immunologic, and neurologic disorders. Some of the most important manifestations and complications of HSV infection are considered here in a neuroanatomic context. This discussion should aid in understanding the pathogenesis and, in some cases, diagnosis and management of associated HSV-related diseases. The sensory nervous system, rather than skin and mucous membranes, is the primary target of HSV infection. With the intention of extending the benefits of acyclovir, valacyclovir is now being explored in a number of HSV-related conditions. This review extends contemporary thinking about how new antiherpetic drugs might be put to greater therapeutic use in the future.

Antiviral Agents↗
PubMed2005

Recurrent antiviral-resistant genital herpes in an immunocompetent patient.

Herpes simplex virus type 2 (HSV-2) resistance to antiviral drugs has been described primarily in immunocompromised patients. We report an apparently immunocompetent, human immunodeficiency virus-negative male patient who has experienced repeated HSV-2 genital outbreaks despite receiving antiviral prophylaxis with several different drugs. Several of the HSV-2 genital isolates from this patient have been confirmed as resistant to acyclovir and penciclovir. Antiviral resistance occurred in the setting of long-term prednisone treatment and intermittent acyclovir prophylaxis at suboptimal doses and persisted despite the cessation of oral steroid treatment. The patient's genital herpes outbreaks were not controlled by high-dose prophylaxis with acyclovir, valacyclovir, and famciclovir. Cessation of antiviral prophylaxis resulted in reversion of this patient's HSV-2 isolates to acyclovir and penciclovir sensitivity, although resistant virus reappeared when antiviral prophylaxis was resumed. Transmission of a sensitive HSV-2 strain from this patient to a female sex partner was observed. These observations confirm previous reports that resistance to acyclovir may develop during prophylactic therapy in an otherwise well, immunocompetent patient. These findings support the conclusion that both drug-sensitive and drug-resistant HSV-2 strains established latency in this patient and that both strains are capable of frequent reactivation.

Acyclovir↗
PubMed2006

Management of herpes simplex virus type 2 infection in HIV type 1-infected persons.

Human immunodeficiency virus type 1 (HIV-1)-infected persons have high rates of herpes simplex virus type 2 (HSV-2) infection, ranging from 50% to 90% in studies of HIV-infected populations from different parts of the world. Genital herpes in persons with HIV type 1 (HIV-1) infection is associated with more-severe and chronic lesions, as well as increased rates of asymptomatic genital shedding of HSV-2. Nucleoside analogues (acyclovir, valacyclovir, and famciclovir) decrease the frequency and severity of HSV-2 recurrences and asymptomatic HSV-2 reactivation and are effective, safe, well-tolerated drugs in patients with HIV-1 infection. These anti-HSV drugs may result in additional clinical and public health benefits for persons with HIV-1 and HSV-2 coinfection by decreasing HIV-1 levels in the blood and genital tract. Given these benefits, HIV-1-infected persons should be routinely tested for HSV-2 infection using type-specific serologic tests. Persons with HSV-2 infection should be offered HSV-2 education and treatment options. Studies to quantify the potential clinical and public health benefits of treating individuals who have HIV-1 and HSV-2 coinfection with anti-HSV therapy are underway.

Antiviral Agents↗
PubMed1999

New therapies and prevention strategies for genital herpes.

Genital herpes is among the most prevalent sexually transmitted diseases. Optimal management of genital herpes includes accurate diagnosis, antiviral therapy, and counseling of patients about complications and transmission of herpes simplex virus (HSV). Antiviral therapy offers significant palliation, and the option of episodic or suppressive treatment should be offered to all patients with genital herpes. Valacyclovir and famciclovir are two newer antiviral agents that are effective and safe for the treatment of genital herpes. Prevention strategies for sexual and perinatal transmission of HSV have not been well defined. Availability of type-specific serological tests for HSV antibodies may assist in identifying persons at risk for acquiring or transmitting HSV infection. Further research is needed to define strategies to prevent the spread of this epidemic infection.

AIDS-Related Opportunistic Infections↗
PubMed2003

Phase I dose escalation clinical trial of adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase in localized and metastatic hormone-refractory prostate cancer.

Osteocalcin (OC), a major noncollagenous bone matrix protein, is expressed prevalently in prostate cancer epithelial cells, adjacent fibromuscular stromal cells, and osteoblasts in locally recurrent prostate cancer and prostate cancer bone metastasis [Matsubara, S., Wada, Y., Gardner, T.A., Egawa, M., Park, M.S., Hsieh, C.L., Zhau, H.E., Kao, C., Kamidono, S., Gillenwater, J.Y., and Chung, L.W. (2001). Cancer Res. 61, 6012-6019]. We constructed an adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase (Ad-OC-hsv-TK) to cotarget prostate cancer cells and their surrounding stromal cells. A phase I dose escalation clinical trial of the intralesional administration of Ad-OC-hsv-TK followed by oral valacyclovir was conducted at the University of Virginia (Charlottesville, VA) in 11 men with localized recurrent and metastatic hormone-refractory prostate cancer (2 local recurrent, 5 osseous metastasis, and 4 lymph node metastasis) in order to determine the usefulness of this vector for the palliation of androgen-independent prostate cancer metastasis. This is the first clinical trial in which therapeutic adenoviruses are injected directly into prostate cancer lymph node and bone metastasis. Results show that (1). all patients tolerated this therapy with no serious adverse events; (2). local cell death was observed in treated lesions in seven patients (63.6%) as assessed by TUNEL assay, and histomorphological change (mediation of fibrosis) was detected in all posttreated specimens; (3). one patient showed stabilization of the treated lesion for 317 days with no alternative therapy. Of the two patients who complained of tumor-associated symptoms before the treatment, one patient with bone pain had resolution of pain, although significant remission of treated lesions was not observed by image examination; (4). CD8-positive T cells were predominant compared with CD4-positive T cells, B cells (L26 positive), and natural killer cells (CD56 positive) in posttreated tissue specimens; (5). levels of HSV TK gene transduction correlated well with coxsackie-adenovirus receptor expression but less well with the titers of adenovirus injected; and (6). intrinsic OC expression and the efficiency of HSV TK gene transduction affected the levels of HSV TK protein expression in clinical specimens. Our data suggest that this form of gene therapy requires further development for the treatment of androgen-independent prostate cancer metastasis although histopathological and immunohistochemical evidence of apoptosis was observed in the specimens treated. Further studies including the development of viral delivery will enhance the efficacy of Ad-OC-hsv-TK.

Adenoviridae↗
PubMed2003

Formulary considerations for drugs used to prevent cytomegalovirus disease.

Four types of therapeutic strategies for managing cytomegalovirus (CMV) in solid organ transplant recipients, the mechanisms of action and efficacy of drugs used for prophylaxis, and the criteria for evaluating drugs for inclusion in a formulary are described. Universal and selective prophylaxis are simple to implement and effective for CMV prophylaxis, but they are costly and patient nonadherence and viral resistance can develop. Preemptive therapy may cause less resistance and cost less, but it is more complex and associated with a higher incidence of infection, which may have no effect on secondary effects from CMV infection, and higher recurrence of disease than prophylactic therapy. Treatment of active disease may be less costly for the drug than other approaches, but intravenous access is required and the rates of infection recurrence and mortality are higher compared with prophylaxis and preemptive therapy. Criteria for deciding which CMV prophylactic drugs to include in a formulary include efficacy, safety, convenience, and cost. CMV immune globulin i.v. is costly and exhibits reduced efficacy when used alone in patients at high risk for CMV disease. Intravenous ganciclovir is effective, but it is costly because of infusion costs. Intravenous drug therapies are inconvenient and associated with a risk of bacterial and fungal infection. Oral acyclovir is safe to use and inexpensive (since a genetic exists), but it has poor efficacy and is inconvenient because of the need for four large daily doses. Valacyclovir is more convenient and with similar safety and probably better efficacy than acyclovir, but it is more costly. Oral ganciclovir and oral valganciclovir have similar safety and costs, with greater efficacy than acyclovir. The single daily dose and lack of resistance to valganciclovir are advantages over oral ganciclovir, which requires three daily doses and can result in the development of resistance.

Administration, Oral↗
PubMed2003

Nodular perianal herpes simplex with prominent plasma cell infiltration.

BACKGROUND: Nodules are exceptional manifestations of herpes simplex virus (HSV) infection in immunocompromised patients. Only two cases of nodular HSV-2 infection of the perianal region have been reported previously. GOAL: The case of a 46-year-old homosexual man with AIDS presenting with painful perianal nodules resembling squamous cell carcinoma is described. STUDY DESIGN: This case report presents details of the histologic findings and treatment regimen. RESULTS: Histologic examination showed the presence of rare multinucleated giant epithelial cells and a dense inflammatory infiltrate composed mostly of plasma cells. Polymerase chain reaction analysis was positive for HSV-2 and negative for HSV-1, cytomegalovirus, Epstein-Barr virus, and human herpesvirus types 6 and 7. After being treated ineffectively with oral acyclovir (4 g/d) for 15 days, the patient was treated with oral valacyclovir (6 g/d), resulting in marked improvement in 10 days and complete resolution after 2 months. CONCLUSIONS: In immunocompromised patients, HSV-2 infection may present with atypical clinical and histopathological features.

AIDS-Related Opportunistic Infections↗
PubMed2001

New developments in the management of cytomegalovirus infection and disease after renal transplantation.

The clinical management of cytomegalovirus infection and disease in renal transplant recipients has recently been significantly improved with the availability of data on prophylaxis with oral ganciclovir and valacyclovir. In addition, significant progress in early diagnosis and the quantitation of viral load has been achieved. The influence of novel immunosuppressants on the clinical course of cytomegalovirus infection has been clarified to some extent by recent clinical data. The identification of risk factors for cytomegalovirus disease beyond seroconstellation and immunosuppression is an ongoing process that might lead to a more targeted use of antiviral agents, given the risk of ganciclovir resistance. The understanding of the effects of cytomegalovirus on long-term graft outcome still needs to be deepened in order to design cytomegalovirus-specific interventions to improve graft survival.

Cytomegalovirus Infections↗
PubMed1998

The Albion Street Centre database, Sydney, Australia.

The Albion Street Centre was established in 1985 as an HIV testing and early management center. More than 22,000 people have been screened for HIV and other blood-borne infections at the Centre, and approximately 3,600 people with HIV/AIDS have been managed there. Approximately 1,600 patients with various stages of HIV disease are currently managed at the Centre by a staff of 60 health care professionals and about 1,000 volunteers. The Albion Street Centre's computer database began recording selected demographic, epidemiologic, clinical, and laboratory characteristics when the first patient presented in 1985. Since then, the complexity and utilization of the database has increased in parallel with improvement in the understanding of the natural history and pathogenesis of HIV infection. Over 100 peer-reviewed publications and presentations have been produced from the database and 45 clinical trials have used the database to identify potential subjects. All data are de-identified and are protected by multiple password codes. Approximately 700 variables are collected from each HIV-positive patient at the initial visit to the Centre and up to 200 variables are added at each subsequent routine clinic visit. The variables collected include the following: standard epidemiologic characteristics; transmission and behavioral parameters, clinical signs and symptoms; laboratory test results; treatments; nutritional history; body composition parameters; psychological assessment results; and management history, including neuropsychological testing. The overall number and characteristics of patients recorded in the database are reported monthly, and are used to plan services, for prevention and educational programs, and as an indicator of the effectiveness of campaigns to encourage HIV-positive people to attend clinics for early management. When these patients have been identified they are invited to participate in the study. Individual patient records are identified and accessed if they meet certain criteria for flagging. For example, patients who have lost more than 5% of their maximal weight are flagged and referred to the dietician for assessment. Further uses for the database are to identify cohorts of patients who are seroconverters and to follow their natural history-the Centre has over 250 patients for whom a documented HIV-positive test has been obtained within 12 months of a documented HIV-negative test; to investigate clinical observations that have been associated with particular drug therapy, e.g., investigation of the reported association between the use of valacyclovir and the thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS)-like complex showed patients with terminal-stage AIDS demonstrated this syndrome independently of their therapy and probably as a consequence of multiorgan failure; and to document the relationship between nutritional intervention and survival, for which use of the database enabled an historical cohort that matched the cases under investigation to be selected. In conclusion, the database is a dynamic and integral part of the assessment, management, and research program of the Albion Street Centre, where it is used by all professional staff.

Adolescent↗
PubMed2005

Renal tubular transporters and antiviral drugs: an update.

Systemic disposition of antiviral drugs partly depends on renal handling of these compounds. There are some known, functionally characterized anionic and cationic transporters with varying substrate specificities for those drugs: human organic anion transporter (OAT) family (hOAT1-3) and human organic cation transporter (OCT) family (hOCT1-3), which mediate the intracellular flux, and adenosine 5'-triphosphate (ATP) binding cassette transporter family (P-glycoprotein, MRP2-5), which mediate the cellular efflux of antiviral drugs. The peptide transporter (PEPT1-2) mediate bi-directional facilitated diffusion of valacyclovir. All these transporters are expressed in the kidney. Organic anion and cation transporters primarily localize to the basolateral membrane of renal epithelial cells while ATP-binding cassette transporters primarily localize to the apical membrane. These transporters work in concert to mediate renal intracellular concentration of occurring antiviral drugs. Along with drug-metabolizing enzymes, these transporters are important determinants of drug effectiveness and toxicity. This review examines the role that these transporters play in renal disposition of antiviral drugs.

ATP Binding Cassette Transporter, Subfamily B↗
PubMedDate not supplied

Infectious disease capsules: a pox on your house.

A 31-year-old, previously healthy white man presented to the emergency department with complaints of malaise, fevers, shortness of breath, a non-productive cough, and a "rash." His physical exam revealed a temperature of 100.2F, a pulse of 129 bpm, respiratory rate of 14 BPM, and blood pressure of 140/74 mm Hg. He was alert, oriented, and in no distress. His oropharynx was dry, his neck was supple, and cervical lymphadenopathy was absent. He had tachycardia, bilateral wheezes, and rhonchi with prolonged expirations. There was a diffuse vesicular eruption enveloping his entire body with involvement sparing his palms and soles (Figures 1 and 2). Laboratory values showed a hemoglobin of 16.0 g/dL and a white blood cell count of 7100 cells/pL, with 39%neutrophils, 23% bands, and 35% lymphocytes. His platelet count was mildly decreased to 86,000 x 103/pL. Chest radiograph revealed bilateral diffuse interstitial infiltrates. A diagnosis of acute varicella-zoster virus pneumonia (varicella pneumonia) was made, and the patient was started on IV acyclovir (10 mg/kg every 8 hours). Upon further questioning, the patient stated that his daughter had been diagnosed with "chickenpox" 7 days ago. The patient had numerous exposures to chickenpox in the past but had never developed clinical expressions of varicella. He was not at risk for HIV infection, not having multiple sexual partners, IV drug abuse, or blood transfusions. During the 1 day of in-hospitalization, his fever abated and the pulmonary signs diminished. Following discharge, IV acyclovir was replaced by valacyclovir to complete a 7-day course of therapy.

Acyclovir↗
PubMedDate not supplied

Treatment options: herpes simplex viruses.

A 35-year-old woman presented with a 1-week history of vesiculopustules on erythematous bases on and in proximity to her lips (Figure 1). The patient had noted burning and itching in the area of these vesiculo-pustules before they developed. She had no systematic symptoms and had not noted similar vesiculopustules in this location in the past. A Tzanck smear was done that revealed multinucleated giant cells. A viral culture was performed. The patient was diagnosed with herpes labialis and received valacyclovir 500 mg b.i.d. for 5 days. One week later, the eruption was noted to have resolved, at which time the results of the viral culture showed growth of Herpes Simplex Virus-1. Thereafter, the patient was lost to follow-up.

Herpes Simplex↗
PubMed2002

Human organic anion transporters and human organic cation transporters mediate renal antiviral transport.

Renal excretion is an important elimination pathway for antiviral agents, such as acyclovir (ACV), ganciclovir (GCV), and zidovudine (AZT). The purpose of this study was to elucidate the molecular mechanisms of renal ACV, GCV, and AZT transport using cells stably expressing human organic anion transporter 1 (hOAT1), hOAT2, hOAT3, and hOAT4, and human organic cation transporter 1 (hOCT1) and hOCT2. Time- and concentration-dependent uptake of ACV and GCV was observed in hOAT1- and hOCT1-expressing cells. In contrast, uptake of valacyclovir, L-valyl ester of ACV, was observed only in hOAT3-expressing cells. On the other hand, AZT uptake was observed in hOAT1-, hOAT2-, hOAT3-, and hOAT4-expressing cells. The Km values of ACV uptake by hOAT1 and hOCT1 were 342.3 and 151.2 microM, respectively, whereas those of GCV uptake by hOAT1 and hOCT1 were 895.5 and 516.2 microM, respectively. On the other hand, the Km values of AZT uptake by hOAT1, hOAT2, hOAT3, and hOAT4 were 45.9, 26.8, 145.1, and 151.8 microM, respectively. In addition, probenecid weakly inhibited the hOAT1-mediated ACV uptake. In conclusion, these results suggest that hOAT1 and hOCT1 mediate renal ACV and GCV transport, whereas hOAT1, hOAT2, hOAT3, and hOAT4 mediate renal AZT transport. In addition, L-valyl ester appears to be important in differential substrate recognition between hOAT1 and hOAT3. hOAT1 may not be the molecule responsible for the drug interaction between ACV and probenecid.

Acyclovir↗
PubMed2003

Prevention of cytomegalovirus disease in recipients of allogeneic stem cell transplants.

The main risk factors for cytomegalovirus (CMV) disease in recipients of allogeneic stem cell transplants (SCT) are recipient CMV seropositivity and acute graft-versus-host disease. Currently, two antiviral strategies, prophylactic or preemptive antiviral treatment, are used for prevention of CMV disease. Preemptive treatment is most favorable when short-term (14-day) treatment is applied. Several methods are available for monitoring of CMV reactivation. PCR-based CMV DNA detection assays are the most sensitive methods; however, the clinical benefit of this high sensitivity is unclear. Even more, there is lack of clarity whether PCR tests can better be performed with plasma, whole blood, or peripheral blood leukocyte samples. Recovery of a CMV-specific CD8(+) cytotoxic-T-lymphocyte (CTL) response is necessary for preventing CMV reactivation and disease. Reconstitution of absolute CMV-specific CTL counts to values above 10 x 10(6) to 20 x 10(6) CTLs/liter is associated with protection from CMV disease. In the near future, preemptive therapy might be withheld in patients with CMV reactivation who are shown to have adequate CMV-specific cytotoxic T-cell levels. Antiviral therapy with (val)acyclovir has been studied only as prophylactic treatment for prevention of CMV infection. High-dose oral valacyclovir is more effective than acyclovir when used in addition to preemptive treatment of CMV reactivation with ganciclovir or foscarnet. Three antiviral drugs have been tested for preemptive therapy of CMV reactivation and/or treatment of CMV disease. Although intravenous ganciclovir is considered the drug of choice, foscarnet has similar efficacy and less toxicity, especially hematologic toxicity. Cidofovir has not been tested extensively, but so far the results are disappointing. Oral valganciclovir for preemptive treatment of SCT recipients is currently being studied. In addition to antiviral therapy, adoptive immunotherapy with CMV-specific cytotoxic T cells as prophylactic or preemptive therapy is a very elegant strategy; however, generation of these cells is expensive and time-consuming, and therefore the therapy is not available at every transplantation center. Magnetic selection of CMV-specific CD8(+) T cells from peripheral blood by using HLA class I-peptide tetramers may be very promising, making this strategy more accessible.

Antiviral Agents↗
PubMed1996

Varicella-zoster virus.

Varicella-zoster virus (VZV) is a ubiquitous human alphaherpesvirus that causes varicella (chicken pox) and herpes zoster (shingles). Varicella is a common childhood illness, characterized by fever, viremia, and scattered vesicular lesions of the skin. As is characteristic of the alphaherpesviruses, VZV establishes latency in cells of the dorsal root ganglia. Herpes zoster, caused by VZV reactivation, is a localized, painful, vesicular rash involving one or adjacent dermatomes. The incidence of herpes zoster increases with age or immunosuppression. The VZV virion consists of a nucleocapsid surrounding a core that contains the linear, double-stranded DNA genome; a protein tegument separates the capsid from the lipid envelope, which incorporates the major viral glycoproteins. VZV is found in a worldwide geographic distribution but is more prevalent in temperate climates. Primary VZV infection elicits immunoglobulin G (IgG), IgM, and IgA antibodies, which bind to many classes of viral proteins. Virus-specific cellular immunity is critical for controlling viral replication in healthy and immunocompromised patients with primary or recurrent VZV infections. Rapid laboratory confirmation of the diagnosis of varicella or herpes zoster, which can be accomplished by detecting viral proteins or DNA, is important to determine the need for antiviral therapy. Acyclovir is licensed for treatment of varicella and herpes zoster, and acyclovir, valacyclovir, and famciclovir are approved for herpes zoster. Passive antibody prophylaxis with varicella-zoster immune globulin is indicated for susceptible high-risk patients exposed to varicella. A live attenuated varicella vaccine (Oka/Merck strain) is now recommended for routine childhood immunization.

Acyclovir↗
PubMed2006

Fulminant, acyclovir-resistant, herpes simplex virus type 2 hepatitis in an immunocompetent woman.

We report an immunocompetent woman with multisystem organ failure following herpes simplex virus type 2 (HSV-2) hepatitis. After she initially responded to intravenous acyclovir, she was switched to oral valacyclovir. She developed respiratory failure and opportunistic infections and died. Autopsy confirmed disseminated HSV infection, and lung tissue grew acyclovir-resistant HSV-2.

Abdominal Pain↗