[Infective complications after liver transplant].
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Bacterial Infections↗
Biomedical subjects
C V Paya
Publications and source records attributed to C V Paya.
Tumor necrosis factor and lymphotoxin secretion by human natural killer cells leads to antiviral cytotoxicity.
NK cells mediate their cytotoxicity against tumor cells through abroad array of cytotoxic and cytostatic proteins. We investigated whether specific proteins could also be identified that contributed to NK cell-mediated antiviral immunity. Human CD16+/CD3- NK cells were obtained by using FACS and subsequently cloned by using limiting dilution. These NK cell lines, which were cytotoxic against NK-sensitive tumor targets and virally infected cells, also generated supernatants that selectively killed vesicular stomatitis virus-infected cells while sparing noninfected cells. This soluble antiviral activity was completely neutralized by antibodies specific for TNF and lymphotoxin. Purified human rTNF also duplicated this specific cytotoxicity against vesicular stomatitis virus-infected cells, as well as against CMV-, Theiler's murine encephalomyelitis virus-, and HSV-infected cells. The degree of cytotoxicity varied for the different viruses and depended on the cell type infected. These results suggest that NK cells can mediate selective and direct cytotoxicity against virally infected cells by the secretion of TNF and lymphotoxin.
Cell Line↗
Efficacy of ganciclovir in liver and kidney transplant recipients with severe cytomegalovirus infection.
Twelve liver and 5 kidney transplant recipients with severe cytomegalovirus infection were treated with Ganciclovir (7.5 mg/kg/day, intravenously). Ten were evaluable (compatible clinical picture, organ involvement shown histopathologically or by culture, viremia, and absence of concomitant infection). All 17 patients were studied for adverse drug side effects. A total of 9 evaluable patients survived the infection; 1 died during treatment due to infection or drug toxicity. A death 19 days after completion of treatment was due to unrelated causes. Patients became afebrile after 2-9 days (mean, 5.3 days) of treatment. Liver function improved, pulmonary infiltrates cleared, and hypoxemia reversed during therapy. Viremia ceased during therapy in 9 patients; asymptomatic viruria persisted or recurred in 6 of 7 patients studied. No relapses occurred during follow-up (7-17 months; mean, 13 months). Transient neutropenia and thrombocytopenia occurred in 3 and 1 patients, respectively. Ganciclovir appears promising for treatment of severe CMV infection in patients with kidney or liver transplants.
Acyclovir↗
Detection of cytomegalovirus from blood leukocytes separated by sepracell-MN and Ficoll-Paque/Macrodex methods.
Two density gradient separation techniques for separation of blood leukocytes were compared for the laboratory diagnosis of cytomegalovirus (CMV) viremia. Of 510 blood specimens processed by both methods, 76 (14.9%) yielded CMV. Of the 76 positive specimens, 66 (87%) and 65 (86%) were processed by the Ficoll-Paque/Macrodex (F-P/M; Macrodex is dextran 70 in normal saline; Pharmacia, Pisataway, N.J.) and Sepracell-MN methods, respectively. Of the 76 CMV-positive blood specimens, 72 (95%) were detected in shell vial cell cultures, whereas only 42 (55%) were detected in conventional tube cell cultures. The time for recognition of specific cytopathic effects due to CMV in tube cell cultures (8.0 versus 7.1 days), the number of fluorescent foci in each positive shell vial culture (19.3 versus 20.1), and the costs of the reagents ($3.50 versus $2.80) were similar and independent of the leukocyte separation method (F-P/M versus Sepracell-MN). Recovery of CMV from heparinized blood (F-P/M method) was similar to that from EDTA-anticoagulated blood (Sepracell-MN method). The Sepracell-MN method is a rapid and sensitive method for detection of CMV from blood specimens and is recommended as a replacement for the more tedious and time-consuming F-P/M procedure.
Cell Separation↗
Evaluation of number of shell vial cell cultures per clinical specimen for rapid diagnosis of cytomegalovirus infection.
Specimens submitted for the diagnosis of cytomegalovirus (CMV) infection were inoculated into three (blood) or two (urine, tissue, bronchoalveolar lavage [BAL]) shell vials seeded with MRC-5 cells for the diagnosis of CMV infection. We evaluated the detection of 993 specimens that were positive for CMV according to the number of shell vial cell cultures inoculated per specimen. For blood cultures, and considering one CMV-positive shell vial as 100%, inoculation of three shell vials versus one increased the detection rate of the virus by 51%. Inoculation of three shell vials compared with two yielded a 20% increase in the detection rate of CMV. For urine, tissue, and BAL specimens, inoculation of two shell vials compared with one resulted in increases of 7, 10, and 5%, respectively. For maximum detection of CMV in shell vial cell cultures, at least three vials should be inoculated with blood specimens, and two vials should be used for urine, tissue, and BAL samples.
Cell Line↗
Management of infection in total knee replacement.
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Anti-Bacterial Agents↗
Laboratory methods for the diagnosis of disseminated histoplasmosis: clinical importance of the lysis-centrifugation blood culture technique.
Disseminated histoplasmosis, an uncommon disease that is usually fatal if not treated, is being recognized with increasing frequency in immunosuppressed patients. We retrospectively reviewed the laboratory methods used to establish the diagnosis of disseminated histoplasmosis in 28 patients examined at our institution. Tissue stains provided the initial diagnosis in 13 of the patients (46%). Serologic tests (complement fixation or immunodiffusion) were positive in 25 patients (89%); the frequencies of positive serologic results were similar in immunocompetent and in immunosuppressed patients. Blood cultures were positive in 20 of the patients (71%) and provided the initial diagnosis in 7 (25%); 5 of these 7 cases (71%) were detected with use of the lysis-centrifugation method. Furthermore, the recovery time for this blood culture method was less than that for a conventional blood culture method (brain-heart infusion biphasic technique). The lysis-centrifugation blood culture technique is an important laboratory method for the diagnosis of disseminated histoplasmosis.
Adult↗
Repeatedly relapsing disseminated histoplasmosis: clinical observations during long-term follow-up.
We report three patients (followed up for 13, 9, and 12 years) who had multiple episodes of disseminated histoplasmosis. Clinically, all three patients had high yields of positive cultures and all developed corticoadrenal insufficiency; all survived the recurrent relapses. One patient had unilateral progressive panophthalmitis, with ocular cultures positive for Histoplasma capsulatum. These relapses occurred despite conventional treatment with large doses of amphotericin B. Prolonged remissions were associated with using small doses of this drug. One patient had a long-term remission while taking ketoconazole daily for more than four years. These patients did not have conditions associated with immunosuppression. Lymphocyte proliferation to mitogens and, in one patient, to histoplasmin, was markedly reduced at the time of relapse and when tested preceding a relapse. All three patients showed a reversal to normal lymphocyte proliferation at the time of the longest last remission.
Female↗
Transient fungemia in acute pulmonary histoplasmosis: detection by new blood-culturing techniques.
Transient fungemia has been thought to occur with acute pulmonary histoplasmosis in humans, but this has never been confirmed. We report two cases of acute pulmonary histoplasmosis in which transient fungemia was detected by the lysis-centrifugation blood-culturing technique. Both patients had self-limited acute pulmonary histoplasmosis, and neither was treated with antifungal therapy. Follow-up evaluation at three years and at 17 months disclosed no evidence of active pulmonary or disseminated disease. Transient Histoplasma capsulatum var. capsulatum fungemia may occur with acute pulmonary histoplasmosis. Fungemia may be prevented or arrested by an intact immune system or by other factors not yet known.
Acute Disease↗
Detection of cytomegalovirus infections in specimens other than urine by the shell vial assay and conventional tube cell cultures.
Blood, bronchoscopy-lavage, biopsy (lung, liver, kidney), sputum, and other (cecum, bone) specimens were inoculated into shell vials and conventional cell tube cultures seeded with MRC-5 cells over a 23-month period. Of 1,472 specimens, 182 (12.4%) yielded cytomegalovirus (CMV)-positive results from 81 patients. Significantly more CMV-positive specimens were detected in shell vials (n = 154; 84.6%) than in conventional tube cell cultures (n = 126; 69.2%) (P less than 0.01). We found that 98 (53.8%) of the total 182 and 41 (42.7%) of the 96 blood specimens positive for CMV were detected by both the shell vial assay and conventional tube cell cultures. However, 56 (30.7%) of the total 182 and 31 (32.3%) of the 96 blood specimens positive for CMV were obtained exclusively in shell vials after detection with monoclonal antibody. Alternatively, 28 (15.4%) of the total 182 and 24 (25%) of the 96 blood specimens positive for the virus were isolated only in conventional tube cell cultures. Thus, although the shell vial assay was more sensitive and rapid than the conventional tube cell culture method, both systems must be used, especially for blood specimens, for the laboratory diagnosis of CMV infections.
Antigens, Viral↗
Human herpesvirus-6 and -7 in transplantation.
Infections with the beta-herpesviruses human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7) are ubiquitous in childhood. The immunosuppression secondary to organ or bone marrow transplantation together with posttransplantation management may favour viral replication and reactivation. HHV-6 and -7 induce immunosuppression by targeting lymphocytes, natural killer cells and monocytes. HHV-6 is commonly detected posttransplantation but variability in definitions of clinical syndromes related to this virus and detection methods have complicated understanding of the clinical relevance of HHV-6 posttransplantation. Clinical symptoms associated with HHV-6 include febrile illness, pneumonitis, hepatitis, encephalitis and bone marrow suppression. However, the majority of HHV-6 infections are asymptomatic. The incidence of HHV-7 infection and its clinical manifestations posttransplantation are even less well characterised. In addition, HHV-6 and HHV-7 are related to CMV disease or acute graft-versus-host disease and, indirectly, to increases in resource utilisation. Based on the potential relevance of these two beta-herpesviruses in transplant recipients, further studies are required to establish their real impact in transplantation. For this, sensitive and specific molecular diagnostic techniques allowing for the rapid detection and quantitation of virus and for the analysis of susceptibility to current antiviral agents are required.
Bone Marrow Diseases↗
Prophylaxis for CMV should now replace pre-emptive therapy in solid organ transplantation.
Cytomegalovirus is a significant cause of morbidity and mortality in transplantation. Controversy exists concerning whether prophylactic or pre-emptive therapy is the optimal strategy for preventing CMV disease. In addition, CMV impacts the transplanted graft, transplant recipient and transplant programme beyond just causing CMV disease; thus questioning whether 'asymptomatic' CMV replication should also be prevented. In this Forum article, prophylactic therapy is advocated as the preferred approach for preventing CMV disease. Prophylactic therapy has a large body of supportive controlled clinical studies demonstrating its efficacy and cost effectiveness. In addition, prophylactic therapy has the benefit of preventing other herpes viruses and other opportunistic superinfections by reducing the immunosuppressive effects of CMV. Moreover, a small but growing body of information suggests that prophylactic therapy may also have a beneficial effect on organ outcomes, including rejection. In contrast, pre-emptive therapy is limited by its reliance on intensive surveillance, which presents logistical difficulties and requires perfect patient compliance. Ambiguity still exists concerning the best surveillance method and its effect on patient-care costs. Each proposed diagnostic approach has limitations, which are affected by the prevalence of CMV in the population studied, the particular assay employed, and the frequency of surveillance. The suggested benefits of pre-emptive therapy, such as decreased cost, fewer adverse medication effects and less antiviral resistance have not been adequately proven in head-to-head clinical studies. We therefore support the proposition that transplant patients at risk for any level of CMV replication will significantly benefit from effective antiviral prophylaxis.
Antiviral Agents↗
Diagnosis of cytomegalovirus hepatitis by histopathology and in situ hybridization in liver transplantation.
Hematoxylin-eosin staining (H&E) of cytomegalovirus (CMV) inclusion bodies was compared with in situ hybridization using a biotinylated DNA probe for the detection of CMV. Of 29 biopsy specimens selected from 23 patients with clinical CMV hepatitis and typical CMV inclusions on histopathologic examination, 23 (79%) were positive by DNA probe and 17 (59%) were detected in cell cultures. The mean number of CMV foci per tissue section was higher by DNA probe (12) compared with H&E (5). We do not recommend in situ hybridization in microbiology laboratories as a replacement for histopathology for the diagnosis of CMV in tissue specimens.
Biopsy, Needle↗
Pretransplantation seronegative Epstein-Barr virus status is the primary risk factor for posttransplantation lymphoproliferative disorder in adult heart, lung, and other solid organ transplantations.
BACKGROUND: The relative importance and interrelationship of risk factors for posttransplantation lymphoproliferative disorder are poorly understood. METHODS: The prospective pretransplantation serologic testing for Epstein-Barr virus of all nonrenal solid organ transplant recipients at our institution made it possible to assess the relative risk for posttransplantation lymphoproliferative disorder in seropositive and seronegative recipients. RESULTS: Fourteen cases of lymphoproliferative disorder were identified in the first 389 consecutive transplant recipients (288 liver, 44 heart, 20 lung, 37 kidney-pancreas) undergoing transplantation from 1985 to 1992 (mean follow-up 33 months). The incidence rates of lymphoproliferative disorder (per 100 person-years) during the first 2 years after transplantation (a period in which all cases occurred) were 1.4 for liver, 2.0 for heart, 6.2 for lung, and 5.2 for kidney-pancreas transplant recipients and were significantly different between liver and lung (p = 0.005) and liver and kidney-pancreas (p = 0.002) groups. Of 367 seropositive patients, lymphoproliferative disorder developed in only three. The incidence rate ratios between seronegative and seropositive recipients were as follows: 76 ([95% confidence interval; 46, 144], p = 0.0000) for any form of lymphoproliferative disorder and 145 ([60, 347], p = 0.0000) for fatal or brain forms. The incidence rate of lymphoproliferative disorder was significantly higher for seronegative recipients who required antilymphocyte antibody therapy for rejection than for those who received none. CONCLUSIONS: The high intrinsic risk for lymphoproliferative disorder in the Epstein-Barr virus seronegative patient, which is amplified by higher levels of immunosuppression, may, in some instances, preclude transplantation.
Acyclovir↗
Exotic viruses and hepatitis.
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Hepatitis Viruses↗