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1/24. Encephalopathy associated with human herpesvirus 6 in a liver transplant recipient.

    Recent reports have documented human herpesvirus 6 (HHV-6) as a cause of high fever, bone marrow depression, and rash in liver transplant recipients in the absence of another known pathogen. We describe a 49-year-old liver transplant recipient who developed confusion, occipital headache, and involuntary movements of the limbs 3 weeks after orthotopic liver transplantation. HHV-6 was detected in the peripheral blood using a rapid culture assay. Examination of cerebrospinal fluid by polymerase chain reaction for HHV-6 was also positive. No other pathogens were identified. The patient improved after commencement of intravenous ganciclovir therapy. This case suggests HHV-6 needs to be considered in the differential diagnosis of unexplained confusion in liver transplant recipients.
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ranking = 1
keywords = herpesvirus
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2/24. Posttransplantation plasmacytic proliferations related to Kaposi's sarcoma-associated herpesvirus.

    Kaposi's sarcoma-associated herpesvirus (KSHV), which was originally detected in Kaposi's sarcoma, also has been found in primary effusion lymphomas (PELs) and some cases of multicentric Castleman's disease. We describe two transplant recipients who developed Kaposi's sarcoma and a spectrum of non-neoplastic lymphoproliferative disorders that show pronounced plasmacytic and plasmacytoid features. The first patient had recurrent pleural effusions and Castleman's disease-like changes in lymph nodes. The second patient had systemic lymphadenopathy and hepatosplenomegaly secondary to diffuse infiltration by polyclonal plasma cells and plasmacytoid B lymphocytes that clinically mimicked Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease. In both cases, KSHV dna was detected by polymerase chain reaction and Southern blotting, and KSHV vIL-6 protein expression was identified in affected tissues by immunohistochemical localization. In contrast, no evidence of KSHV coinfection was detected in any of 31 EBV-related posttransplant lymphoproliferative disorders or 112 non-PEL lymphomas tested. The pathologic findings in these two patients were not representative of malignancy by morphologic, immunophenotypic, or molecular criteria. This study underscores the marked propensity for hematolymphoid proliferations associated with KSHV infections to show plasmacytic features. Additionally, this study describes use of an antibody reactive against KSHV vIL-6 that can readily detect a subpopulation of KSHV-infected hematopoietic cells.
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ranking = 1
keywords = herpesvirus
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3/24. Molecular evidence of organ-related transmission of Kaposi sarcoma-associated herpesvirus or human herpesvirus-8 in transplant patients.

    In transplant patients, Kaposi sarcoma (KS)-associated herpesvirus or human herpesvirus-8 (HHV-8) infection is associated with the development of KS, primary effusion lymphoma and Castleman disease. Whether HHV-8 is either reactivated in the recipient or transmitted by the donor has been investigated so far only by serologic studies. Thus, we addressed the issue of HHV-8 transmission in the transplantation setting by molecular methods. We exploited the high level variability of the orf-K1 gene and the polymorphism of the orf-73 gene of the HHV-8 genome to assess the genetic relatedness of the HHV-8 strains identified in the posttransplant KS lesions that developed, simultaneously, 20 months after transplantation, in 2 recipients of twin kidneys from the same cadaver donor. The 100% identity of nucleotide sequence of the most variable viral region and the presence of the same, single orf-73 type in both patients provides strong molecular evidence of organ-related transmission of HHV-8 in the setting of transplantation.
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ranking = 2
keywords = herpesvirus
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4/24. Pleural posttransplantation lymphoproliferative disorder following liver transplantation.

    A case of posttransplantation lymphoproliferative disorder (PTLD) involving the pleura is reported. The patient was a 57-year-old man who underwent liver transplantation 2 years prior to the development of PTLD. The PTLD was pleural-based and was first detected by radiologic studies as a pleural effusion. Transbronchial biopsy and cytologic examination of 2 pleural fluid specimens were nondiagnostic. Subsequent open-wedge biopsy revealed a monomorphic PTLD, composed of large immunoblasts with plasmacytoid differentiation. Immunohistochemical studies demonstrated B-cell lineage with expression of monotypic cytoplasmic immunoglobulin kappa light chain and CD79a, and absence of T-cell antigens. Immunohistochemical and in situ hybridization studies demonstrated Epstein-Barr virus protein and rna, respectively. No evidence of human herpesvirus 8 dna was detected by polymerase chain reaction. We report this case because pleural-based PTLD is rare. The diagnosis of this entity is made more difficult by the fact that PTLD is often underrepresented in pleural fluid cytology samples.
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ranking = 0.2
keywords = herpesvirus
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5/24. Primary human herpesvirus 6 infection in liver transplant recipients.

    We detected primary human herpesvirus 6 (HHV-6) infection in 5 infants who received living related liver transplantation from their HHV-6 seropositive mothers. Primary HHV-6 infection was confirmed by demonstrating the seroconversion of HHV-6 antibodies with an immunofluorescence assay, by the isolation of the virus, or both. Seroconversion of HHV-6 immunoglobulin g antibody was demonstrated in all 5 recipients. HHV-6 was isolated from 3 of the 5 recipients between 2 and 3 weeks after transplantation. Moreover, the virus genome was detected in plasma by polymerase chain reaction in 4 of the 5 recipients during the same period. Although the 5 recipients had pyrexia at the time of primary HHV-6 infection, none of the recipients had a skin rash after defervescence. Clinical symptoms disappeared without specific antiviral treatment in all but 1 of the recipients.
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ranking = 1
keywords = herpesvirus
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6/24. Delayed facial palsy after stapedectomy.

    OBJECTIVE: To study the incidence, pathogenesis, and prevention of delayed facial palsy after stapedectomy. STUDY DESIGN: Retrospective case review. SETTING: Otology/neurotology referral center. patients: A series of 2152 stapedectomy procedures in 2106 patients over 12 years. INTERVENTION: Delayed facial palsy after stapedectomy was studied. MAIN OUTCOME MEASURE: House-Brackmann facial nerve grading system and serum antibody titer tests for herpes simplex virus type I and type II, and varicella zoster virus. RESULTS: Delayed facial palsy occurred in 11 of 2152 procedures. Delayed facial palsy occurred from 5 to 16 days (mean 8) after stapedectomy. Predisposing factors were bony facial canal dehiscence with bare or bulging facial nerve herniation in 5 patients; chorda tympani nerve stretched, manipulated, or cut in 2 patients; granulomatous reaction to Gelfoam in 1 patient; fever blisters on the upper lip in 1 patient; and sinusitis in 2 patients. Elevated anti-varicella antibody titers were found in all 6 patients studied. Anti-herpes simplex type I and II antibody titers were elevated in 5 of 6 patients. acyclovir was effective in preventing delayed facial palsy in 1 patient who had undergone revision stapedectomy and experienced delayed facial palsy after previous stapedectomy in the same ear with elevated anti-herpes antibody titer. CONCLUSIONS: Delayed facial palsy occurred in 0.51% of patients after stapedectomy. Serologic investigation suggests activation of latent herpesvirus. Mechanical irritation of the facial or chorda nerve during operation may trigger the activation. The anti-herpesvirus agent acyclovir may prevent delayed facial palsy after stapedectomy in patients suspected of having this complication.
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ranking = 0.4
keywords = herpesvirus
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7/24. Fulminant disseminated Varicella Zoster virus infection without skin involvement.

    BACKGROUND: Varicella Zoster virus (VZV) infection is potentially very serious in bone marrow transplant recipients, and may manifest as a disseminated visceral infection. This condition is generally accompanied by a vesicular rash. OBJECTIVES: We review here a case of fulminant fatal disseminated VZV infection, not accompanied by skin involvement, and the laboratory approaches currently available to diagnose this disease. STUDY DESIGN: Post mortem tissue samples were subjected to histopathological examination, and tested for herpesviruses by electron microscopy and PCR. RESULTS: Intranuclear inclusions were noted by histological examination in the lungs, liver, kidneys and bone marrow. Particles with a herpesvirus morphology were visualized in liver tissue. VZV dna was detected in liver and bone marrow by PCR followed by sequencing of the amplicons. viremia was documented by retrospective testing of the serum by PCR. CONCLUSIONS: A disseminated VZV infection which proved rapidly fatal was demonstrated in a case without skin manifestations. This rare presentation of VZV infection is potentially underdiagnosed. Testing for VZV viremia by PCR can at the very least suggest the diagnosis although whether plasma-associated viremia is truly pathognomonic of visceral disseminated infection remains to be established.
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ranking = 0.4
keywords = herpesvirus
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8/24. Human herpesvirus 7-associated meningitis and optic neuritis in a patient after allogeneic stem cell transplantation.

    A 9-year-old boy who received allogeneic stem cell transplantation began to vomit from day 10 after transplantation. In addition to vomiting, the patient had a fever (from day 26) and severe headache (from day 34). His cerebrospinal fluid (CSF) (day 41) demonstrated pleocytosis with an absence of leukemic cells. Although the patient's symptoms were resolved with further supportive care, abrupt onset of bilateral decreased vision occurred at day 54. He was diagnosed with bilateral optic neuritis, due to the presence of disc edema and redness. Concomitant with the occurrence of aseptic meningitis, the human herpesvirus 7 (HHV-7) antibody titer increased significantly in this patient. Although neither HHV-6 nor cytomegalovirus (CMV) dna was detected in CSF collected at day 41, HHV-7 dna was detected in the sample. Viral dna was not detected in CSF collected at day 93.
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ranking = 1
keywords = herpesvirus
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9/24. Conversion to sirolimus: a successful treatment for posttransplantation Kaposi's sarcoma.

    The increased incidence of Kaposi's sarcoma (KS) in organ transplantation has been related to the KS herpesvirus and the permissive effect of immunosuppressive therapy. calcineurin inhibitors are the cornerstone of immunosuppression in organ transplantation, although they could promote tumor progression. In contrast, sirolimus, a new immunosuppressive agent, exhibits potent antitumor activity. We postulated that conversion from cyclosporine to sirolimus in patients with KS could favor regression of KS lesions without increasing the risk of graft rejection. Two renal transplant recipients with KS underwent conversion from cyclosporine to sirolimus. Both patients showed complete regression of KS lesions and excellent clinical and functional results. sirolimus offers a new and promising approach to the management of posttransplantation KS and probably to other types of malignancies in organ transplant recipients.
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ranking = 0.2
keywords = herpesvirus
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10/24. Visceral Kaposi's sarcoma associated with human herpesvirus 8 seroconversion in a heart transplant recipient.

    A close association between human herpesvirus-8 (HHV-8) and Kaposi's sarcoma (KS) has been shown in transplant recipients, but donor-to-recipient transmission of HHV-8 is uncommon. Herein we report a case of a heart transplant recipient who had a fatal visceral KS in association with HHV-8 seroconversion at 18 months after transplantation with a donor having positive serology discovered after transplantation.
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ranking = 1
keywords = herpesvirus
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