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 11,398 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two distinct processes contribute to the spectrum of human cytomegalovirus (HCMV)-induced pathology. In the first instance, cytopathic effects appear to occur as a direct result of virus replication. This type of disease is characterized by persistent HCMV infection of neural or gastrointestinal tissue, which results in HCMV retinitis, encephalitis, hepatitis, or gastroenteritis. Direct cytopathic effects of HCMV are associated with congenitally acquired or acquired immune deficiency syndrome-related manifestations of HCMV infection. A second type of HCMV-associated disease process is driven by immunopathologic mechanisms and results in variable mononucleosis-like syndromes and/or pneumonia in normal or partially immunosuppressed individuals. Human cytomegalovirus-associated interstitial pneumonia appears to derive from a combination of these two types of disease processes. Here, persistent viral infection, immunopathologic mechanisms, and virus-induced expression or repression of cellular genes each constitutes an important factor in pathogenesis. An understanding of the multiple underlying mechanisms of pathogenesis is crucial to devising optimum treatment approaches.
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PMID:Epidemiology and pathogenesis of cytomegalovirus disease. 216 Jan 29

The clinical manifestations of cytomegalovirus (CMV) infection in persons with AIDS are described, and recent advances in the management of these syndromes with antiviral agents are reviewed. CMV infection is the most common serious opportunistic viral infection in AIDS patients. Clinical manifestations include chorioretinitis, gastroenteritis, hepatitis, pneumonia, CNS infection, adrenalitis, and a wasting syndrome. The diagnosis of CMV infection requires laboratory demonstration of a serologic response to the virus, detection of viral components or products, or isolation of the virus. Ganciclovir is an acyclic nucleoside analogue marketed for the treatment of CMV-related retinitis in immunocompromised hosts. After i.v. ganciclovir induction therapy, more than 80% of patients show improvement or stabilization of retinitis. Relapse is common in AIDS patients, however, and low-dose i.v. maintenance therapy is recommended. The most serious dose-limiting effect is neutropenia. Intravitreal injection of ganciclovir has been well tolerated and efficacious. Ganciclovir has shown some efficacy in the treatment of other life-threatening CMV infections, especially gastroenteritis, but data are limited. Ganciclovir-resistant strains have been reported. Foscarnet, a pyrophosphate analogue with activity against both human CMV and human immunodeficiency virus, is undergoing clinical trials. Foscarnet has shown promise in the therapy of CMV-related retinitis, but results for other CMV infections are disappointing. Nephrotoxicity is the major dose-limiting effect. AIDS patients with sight-threatening and rapidly progressive CMV-related retinitis should be treated with ganciclovir. Foscarnet may offer an alternative when it becomes available. More must be learned about the efficacy of these drugs in the treatment of CMV infection in patients with AIDS.
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PMID:Management of cytomegalovirus infection in patients with acquired immunodeficiency syndrome. 216 89

Cytomegalovirus (CMV) infection in patients with the acquired immunodeficiency syndrome (AIDS) can present as either disseminated disease, pneumonitis, retinitis, gastroenteritis, neuropathy, or a subclinical infection. We report a patient whose initial manifestation of CMV infection was severe central airways obstruction due to necrotizing tracheitis. At bronchoscopy, the lesion appeared deeply ulcerated, distinctly different from previously described airway lesions in patients with AIDS. Mucosal biopsies showed characteristic intranuclear and intracytoplasmic inclusions and cultures yielded only CMV. The patient responded partially to ganciclovir, steroids, and antibiotics against suspected anaerobic superinfection but died as a result of central nervous system disease believed due to toxoplasmosis or lymphoma. CMV infection of the upper airway should be considered in the patient with AIDS presenting with atypical cough or stridor and ulcerated endobronchial lesions.
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PMID:Central airway obstruction due to cytomegalovirus-induced necrotizing tracheitis in a patient with AIDS. 217 87

Human cytomegalovirus (CMV) has several possible roles in the pathogenesis of AIDS. CMV causes a number of clinical syndromes, including retinitis, pneumonitis, and gastroenteritis in patients infected with human immunodeficiency virus type 1 (HIV-1). In addition, CMV may potentiate the cellular immunodeficiency observed in patients with HIV infection either directly or through enhancement of HIV replication. Finally, CMV may predispose the host to bacterial or fungal infection by compromising the integrity of mucosal barriers to infection. Therapy with ganciclovir for CMV infection may result in a decrease in morbidity related to the virus, but problems with drug toxicity and resistance to the agent mandate the development of additional therapeutic approaches.
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PMID:Cytomegalovirus in the setting of infection with human immunodeficiency virus. 164 83

Cytomegalovirus (CMV) can be an important opportunistic infection in HIV-1-infected patients, particularly when the CD4+ T-cell count drops below 50 lymphocytes/mm3. CMV-associated disease, including retinitis, pneumonitis, gastroenteritis, and encephalitis, is estimated to affect up to 40% of AIDS patients. We have studied the cellular immune response to CMV in gut-associated lymphoid tissue (GALT) of HIV-1-infected patients. Two patients with chronic diarrhea of unknown etiology were examined by flexible sigmoidoscopy and upper endoscopy. Biopsy specimens were obtained from lymphoid-associated tissue sites in rectum and duodenum. Both patients were seropositive for CMV IgG, but had not been treated with ganciclovir, and neither had clinical signs of CMV disease. Mononuclear cell cultures were established from GALT and blood and assayed for the presence of CMV-specific CD8+ T cells. CD8+ T-cell phenotype and function were assessed by MHC Class I tetramer staining, using an HLA-A*0201 tetramer complex specific for peptide 495-503 (NLVPMVATV) of CMV lower matrix protein pp65, and by a standard 51Cr release assay. CMV pp65-specific cytotoxic lymphocytes (CTL) were detected in GALT and blood MNC from both patients. These results demonstrate that HIV-1-infected subjects seropositive for CMV, but without active CMV gastrointestinal disease, harbor CMV-specific CTL in intestinal lymphoid tissue. This is the first report of isolation of CMV-specific CTL in GALT and will lead to greater understanding of the pathogenesis of CMV disease in human mucosal tissue.
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PMID:Isolation of cytomegalovirus-specific cytotoxic T-lymphocytes from gut-associated lymphoid tissue (GALT) of HIV type 1-infected subjects. 1095 91

We have prospectively evaluated the efficacy of real-time PCR-guided preemptive therapy for CMV diseases in allogeneic hematopoietic stem cell transplant recipients with grades II-IV acute GVHD. The dose of ganciclovir was adjusted according to the viral load determined by real-time polymerase chain reaction (PCR). On detecting CMV reactivation in the plasma, ganciclovir was initiated at a dose of 5 mg/kg body weight once daily, and the dose was increased to twice daily if viral load continued to increase after initiating ganciclovir. In 39 evaluable patients, CMV reactivation assessed by real-time PCR became positive in 30 (77%). One developed CMV gastroenteritis before PCR became positive. Thus the remaining 29 patients were treated preemptively with ganciclovir. The dose of ganciclovir was increased in 12 patients (41%) of preemptively treated patients for increasing viral load. CMV diseases were diagnosed in two patients (one gastroenteritis and one retinitis), and late CMV disease was diagnosed in one patient (gastritis). The treatment was generally well-tolerated, but three patients (10%) developed neutropenia (neutrophil count less than 1.0 x 10(9)/l). In conclusion, real-time PCR-guided preemptive therapy with decreased dose of ganciclovir is feasible and does not increase the frequency of CMV diseases if the dose is adjusted according to the viral load.
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PMID:Dose-adjusted preemptive therapy for cytomegalovirus disease based on real-time polymerase chain reaction after allogeneic hematopoietic stem cell transplantation. 1204 Apr 76

Cytomegalovirus (CMV) infection is an important contributor to the morbidity and mortality associated with bone marrow transplantation (BMT). Infection may lead to CMV disease involving multiple organs such as pneumonia, gastroenteritis, retinitis, central nervus system involvement and others. CMV seropositivity is an important risk factor and approximately half of BMT recipients will develop clinically significant infection most commonly in the first 100 d post-transplant. The commonly used tests to diagnose CMV infection in these patients include the pp65 antigenemia test and the CMV DNA polymerase chain reaction (PCR) assay. Because of its greater sensitivity and lesser turnaround time, the CMV PCR is nowadays the preferred test and serves as a main guide for pre-emptive therapy. Methods of CMV prevention include use of blood products from seronegative donors or leukodepleted products. Prophylaxis or pre-emptive therapy strategies for CMV prevention may be used post-transplant with the latter becoming more common. The commonly used antivirals for pre-emptive therapy and CMV disease management include intravenous gancyclovir and foscarnet. The role of intravenous immunoglobulin, although used commonly in CMV pneumonia is not clear.
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PMID:Cytomegalovirus infection in the bone marrow transplant patient. 2672 56

Various types of infectious complications could develop after allogeneic hematopoietic stem cell transplantation (HSCT) due to the associated intensive immunosuppression. Cellular immunity is also impaired, resulting in a higher incidence of viral infections when compared with standard chemotherapy. Cytomegalovirus (CMV) reactivates in seropositive patients under immunosuppression after allogeneic HSCT, causing complications, such as pneumonitis, gastroenteritis, and retinitis. Because intervention before the onset of disease, rather than after, can improve prognosis, preemptive therapy guided by early detection of CMV reactivation has been extensively used. Recently, the introduction of a less myelotoxic agent, letermovir, has enabled prophylactic therapy to be administered safely and effectively. In addition, prophylactic letermovir is expected to reduce transplant-related mortality. However, the onset of CMV infection/disease as either a breakthrough infection or after the discontinuation of letermovir is still problematic. In this section, the management tips for CMV infection after allogeneic HSCT have been summarized.
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PMID:[Management of cytomegalovirus infection after hematopoietic stem cell transplantation]. 3159 61

Cytomegalovirus (CMV) can cause end-organ diseases including pneumonia, gastroenteritis, retinitis, and encephalitis in hematopoietic stem cell transplantation recipients. Potential differences among different CMV diseases remain uncertain. This study aimed to compare the clinical characteristics, risk factors, and mortality among different CMV diseases. A retrospective nested case-control study was performed based on a cohort of 3862 patients who underwent haploidentical hematopoietic stem cell transplantation at a single-center. CMV diseases occurred in 113 (2.92%) of 3862 haplo-HSCT recipients, including probable CMV pneumonia (CMVP, n = 34), proven CMV gastroenteritis (CMVG, n = 34), CMV retinitis (CMVR, n = 31), probable CMV encephalitis (CMVE, n = 7), and disseminated CMV disease (Di-CMVD, n = 7). Most (91.2%) cases of CMVG developed within 100 days, while most (90.3%) cases of CMVR were late onset. Refractory CMV infection and CMV viral load at different levels were associated with an increased risk of CMVP, CMVG, and CMVR. Compared with patients without CMV diseases, significantly higher non-relapse mortality at 1 year after transplantation was observed in patients with CMVP and CMVR, rather than CMVG. Patients with CMVP, Di-CMVD, and CMVE had higher overall mortality after diagnosis than that of patients with CMVG and CMVR (61.7%, 57.1%, 40.0% vs 27.7%, 18.6%, P = 0.001). In conclusion, the onset time, viral dynamics, and mortality differ among different CMV diseases. The mortality of CMV diseases remains high, especially for CMVP, Di-CMVD, and CMVE.
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PMID:Comparison of different cytomegalovirus diseases following haploidentical hematopoietic stem cell transplantation. 3273 50