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Biomedical subjects

J C Mendez

Publications and source records attributed to J C Mendez.

9 recordsLinked to original sources

Human beta-herpesvirus interactions in solid organ transplant recipients.

The replication of beta-herpesviruses-cytomegalovirus (CMV), human herpesvirus (HHV)-6, and HHV-7-and their association with CMV disease and response to antiviral therapy were prospectively investigated in 33 liver transplant recipients not given antiviral prophylaxis. CMV, HHV-6, and HHV-7 DNA were detected within 8 weeks after transplantation in 70%, 33%, and 42% of the patients, respectively. The univariate association between CMV disease and the 3 beta-herpesviruses was more significant by virus load quantitation than by qualitative detection of DNA. This association with high levels of CMV, HHV-6, and HHV-7 (P<.001,.022, and.001, respectively) occurred mainly in CMV-seronegative recipients of transplants from CMV-seropositive donors. Antiviral therapy with ganciclovir (Gcv) reduced the load of CMV and HHV-6 and HHV-7. These results suggest that CMV disease in transplant recipients is related to the unique interaction of the 3 beta-herpesviruses and is ultimately reduced after intravenous Gcv treatment.

Antibodies, Viral↗

Relationship of HHV8 replication and Kaposi's sarcoma after solid organ transplantation.

HHV8 DNA sequences have recently been isolated from all types of Kaposi's sarcomas, and its association in the etiopathogenesis of this tumor has been established. However, little is known about the regulation of HHV8 replication in immunocompromised patients seropositive for this virus, and its impact on the development of Kaposi's sarcoma (KS). Through the study of a heart transplant patient who developed KS and in whom peripheral blood lymphocytes (PBLs) had been prospectively collected before and after transplantation, we have investigated the pathogenesis of HHV8. Our results indicate that (i) HHV8 can reactivate soon after transplantation; (ii) viral replication, as determined by quantification of HHV8 DNA load of PBLs, increases significantly after transplantation; and (iii) increased HHV8 DNA levels in PBLs are associated with the development of KS.

DNA, Viral↗

Novel mutation in the CMV UL97 gene associated with resistance to ganciclovir therapy.

Cytomegalovirus (CMV) strains resistant to ganciclovir have been associated with specific mutations in the UL97 and UL54 genes. The UL97 gene of a CMV strain isolated from a renal transplant recipient before and after 438 days of ganciclovir treatment was amplified by polymerase chain reaction and sequenced. A novel mutation resulting in deletion of codons 595 to 603 was identified in the viral DNA from specimens obtained after, but not before, prolonged ganciclovir therapy. Clinical and virological resolution of CMV disease occurred after switching to foscarnet therapy. Although many ganciclovir resistance mutations have been mapped to the UL97 codon range 591-607, this one is unusual in that it involves deletion of half these codons. Because UL97 seems to be necessary for effective CMV replication, this deletion suggests that much of codons 591-607 can be removed without destroying the biological function of UL97, and that this codon range can be altered in various ways to affect ganciclovir susceptibility. Rapid, flexible genotypic assays directed at this part of UL97 may facilitate the early recognition of ganciclovir resistance.

Adult↗

Human herpesvirus 6 seronegativity before transplantation predicts the occurrence of fungal infection in liver transplant recipients.

BACKGROUND: Invasive fungal infection has a major impact on the morbidity and mortality of liver transplant recipients. Human herpesvirus (HHV)-6 infection after transplantation is associated with an immunosuppressive state and the development of cytomegalovirus disease. Because cytomegalovirus infection is a risk factor for invasive fungal infection after transplantation, we have examined whether HHV-6 and fungal infection are associated after transplantation. METHODS: Pretransplantation sera from 247 consecutive liver transplant recipients were analyzed for IgG to HHV-6. Thirty-three (13%) HHV-6-seronegative recipients were identified. Six of 33 (18%) seronegative recipients experienced fungal infection as compared with 15 of 214 (7%) seropositive recipients (P=0.034). RESULTS: In a univariate analysis of risk factors for fungal infection, pretransplantation seronegativity to HHV-6 (P=0.034), intraoperative cryoprecipitate requirements greater than the 75th percentile (P=0.035), reoperation (P=0.005), biliary stricturing postoperatively (P=0.046), and gastrointestinal or vascular complications postoperatively (P=0.030) were identified as significant risk factors. Moreover, in pairwise multivariate analysis, pretransplantation HHV-6 seronegativity remained a significant variable even in the presence of each of the other variables. CONCLUSIONS: These results suggest that HHV-6 seronegativity before transplantation is a valuable clinical marker that identifies patients at risk for developing fungal infection after transplantation.

Disease-Free Survival↗

Diagnostic value of a miracidium in urinary sediment.

Although rarely encountered in the United States, urinary tract schistosomiasis occurs commonly in many countries in the eastern hemisphere. Travel and immigration may contribute to imported cases of schistosomiasis. Excessive morbidity and increased mortality, including the development of urinary-tract squamous-cell carcinoma, are associated with untreated Schistosoma haematobium infection. Therefore, in the appropriate clinical context, all efforts should be made to rule out infectious and readily treatable causes of chronic hematuria. The presence of characteristic eggs in the urinary sediment is the usual means of diagnosing a S. haematobium infection. Additionally, the small and less commonly encountered miracidium stage of S. haematobium may also be present in the urine, which is another means of diagnosing urinary tract schistosomiasis. The present report describes a case in which a miracidium was detected in a fresh, unstained urine specimen. As detection of miracidia can be made in specimens also processed by routine cytologic methods, it behooves cytologists to be aware of this entity for the diagnosis of schistosomiasis.

Adolescent↗

Evaluation of PCR primers for early diagnosis of cytomegalovirus infection following liver transplantation.

The availability of microbiologic methods that detect early replication of cytomegalovirus (CMV) posttransplantation will enhance the process of initiating preemptive antiviral therapy prior to the appearance of CMV disease. Using PCR techniques we sought to determine which region of the CMV genome present in peripheral blood leukocytes (PBLs) or serum provides the highest sensitivity for the detection of CMV posttransplantation. Blood samples were prospectively collected weekly for at least 8 weeks from a cohort of 21 consecutive liver transplant recipients not receiving anti-CMV prophylaxis. Results of PCR assays were correlated with recovery of CMV in cell cultures and histopathological findings from biopsy specimens of infected organs to assess clinical symptomatic infection. Of 148 specimens, primer pairs directed to the HindIII-X fragment region of CMV detected target DNA with a 94% sensitivity, compared to an 87% sensitivity with primer pairs directed to EcoRI fragment D, 32% sensitivity with primer pairs directed to the immediate-early antigen 1 gene (IEA1 gene), and 20% sensitivity with primer pairs directed to the major immediate-early (MIE) gene. The performance characteristics in terms of the sensitivity of primers for amplifying CMV DNA associated with symptomatic infection ranged from 100% (HindIII-X) to 20% (MIE gene); however, specificity was inversely related (HindIII-X, 45%; MIE gene, 91%) to primers directed to these gene targets. When HindIII-X and EcoRI-D primer sets were used, CMV DNA from PBLs was a more sensitive target than CMV DNA from serum for the early detection of symptomatic CMV infection (17 versus 12 days). Importantly, CMV DNA was not detected in five patients with no evidence of this viral infection. In conclusion, primers directed to the HindIII-X fragment region were the most optimal for the early detection of CMV DNA in PBLs and sera from symptomatic liver transplant recipients.

Antibodies, Viral↗

Detection and semiquantitative analysis of human herpesvirus 8 DNA in specimens from patients with Kaposi's sarcoma.

Kaposi's sarcoma (KS) is the most common neoplasm in patients with AIDS. Epidemiologic evidence and the recent identification of herpesvirus-like DNA sequences in patients with KS have suggested a role for viral agents in the etiopathogenesis of this disease. It is unclear if these sequences are present in all types of KS and if the copy number of these sequences has a correlation with disease severity (staging). In order to clarify these issues, we retrospectively analyzed, by PCR and Southern blotting, formalin-fixed, paraffin-embedded biopsy specimens from 12 patients previously diagnosed with KS by histopathologic examination of these specimens between the years of 1977 and 1996. We also analyzed tissue samples from these patients taken from dermal sites without KS lesions and control tissues from healthy subjects. Of the 12 patients, 6 had classic KS, 5 had AIDS-associated KS, and 1 had the endemic type of KS. We tested the specimens for other herpesviruses, including cytomegalovirus, human herpesvirus 6 (HHV-6), HHV-7, HHV-8, and Epstein-Barr virus. Of 20 biopsy specimens from patients previously diagnosed with KS, 19 were positive for HHV-8 sequences (95%), while PCR for the DNAs of other herpesvirus agents was negative. Uninvolved tissue from these patients and control tissue from healthy subjects gave negative results for all viruses. Semiquantitative analysis of Southern blots showed higher levels of HHV-8 DNA in those patients with multicentric and visceral involvement than in those patients with localized involvement. In addition, in patients with localized skin disease, the nodular stage had higher levels of HHV-8 DNA than the patch or plaque stages. Our data confirmed that HHV-8 is involved in the etiopathogenesis of all types of KS and that there is a correlation between HHV-8 DNA load and the severity and staging of this disease.

AIDS-Related Opportunistic Infections↗

Comparative studies of two systems of prophylactic antibiotics in head and neck surgery.

One hundred and seventeen patients undergoing operations on the head and neck were investigated for the causes of infection. There was a close relationship between the pre-operative culture and the risk of infection. There was a greater risk of infection (10.7%) when the pharynx was opened than when it was not (0.0%). The operations most liable to infection are laryngopharyngectomy and those in which skin flaps are used. The isolation of pathogenic bacteria in the operative exudate did not in general predispose to the development of infection, which did not occur when these cultures were negative. Positive cultures obtained from the drain on 3 consecutive days were a significant indication that infection will probably occur.

Anti-Bacterial Agents↗