Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus: population based study of coronary heart disease.
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OBJECTIVE: To study possible associations between coronary heart disease and serological evidence of persistent infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus. DESIGN: Population based, case-control study, nested within a randomised trial. SETTING: Five general practices in Bedfordshire, UK. INDIVIDUALS: 288 patients with incident or prevalent coronary heart disease and 704 age and sex matched controls. RESULTS: High concentrations of serum IgG antibodies to H pylori were present in 54% of cases v 46% of controls, with corresponding results for C pneumoniae seropositivity (33% v 33%), and cytomegalovirus seropositivity (40% v 31%). After adjustments for age, sex, smoking, indicators of socioeconomic status, and standard risk factors, the odds ratios (95% confidence intervals) for coronary heart disease of seropositivity to these agents were: 1.28 (0.93 to 1.75) for H pylori, 0.95 (0.66 to 1.36) for C pneumoniae, and 1.40 (0.96 to 2. 05) for cytomegalovirus. CONCLUSIONS: There is no good evidence of strong associations between coronary heart disease and serological markers of persistent infection with H pylori, C pneumoniae, or cytomegalovirus. To determine the existence of moderate associations between these agents and disease, however, larger scale studies will be needed that can keep residual confounders to a minimum. (+info)
The clinical utility of CMV surveillance cultures and antigenemia following bone marrow transplantation.
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At our institution, the cytomegalovirus (CMV) prophylaxis protocol for allogeneic bone marrow transplant (BMT) recipients who are CMV-seropositive or receive marrow from a CMV-seropositive donor consists of a surveillance bronchoscopy approximately 35 days posttransplant. Patients with a positive surveillance bronchoscopy for CMV receive pre-emptive ganciclovir. In order to determine the utility of other screening methods for CMV, we prospectively performed weekly CMV antigenemia, and blood, urine and throat cultures from time of engraftment to day 120 post-BMT in 126 consecutive patients. Pre-emptive ganciclovir was given to 11/81 patients (13.6%) because of a positive surveillance bronchoscopy for CMV. Results of CMV blood, urine and throat cultures and the antigenemia assay done prior to or at the time of the surveillance bronchoscopy were analyzed for their ability to predict the bronchoscopy result. The antigenemia test had the highest positive and negative predictive values (72% and 96%, respectively). The ability of these tests to predict CMV disease was evaluated in the 70 patients with a negative surveillance bronchoscopy who did not receive pre-emptive ganciclovir. Of 19 cases of active CMV disease, CMV antigenemia was positive in 15 patients (79%) a mean of 34 days preceding symptoms. Blood cultures were positive in 14/19 patients (74%) a mean of 31 days before onset of disease. CMV antigenemia is useful for predicting the surveillance bronchoscopy result, and also predicts the development of CMV disease in the majority of patients missed by the surveillance bronchoscopy. (+info)
Cytomegalovirus associated neonatal pneumonia and Wilson-Mikity syndrome: a causal relationship?
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Lung injury caused by intrauterine inflammation has recently been strongly implicated in the pathogenesis of Wilson-Mikity syndrome (WMS). This article supports this theory by suggesting a causative role of intrauterine cytomegalovirus (CMV) infection for the development of WMS. A male premature infant, born at 33 weeks of gestational age, developed chronic lung disease compatible with WMS and diagnostic evaluation was positive for CMV infection. High-resolution computed tomography scan and lung histology revealed typical features of WMS in association with signs of interstitial pneumonia. CMV was found in urine, breastmilk, bronchoalveolar lavage material and lung tissue from open lung biopsy. Follow-up after treatment with ganciclovir and steroids showed resolving lung disease at the age of 6, 10 and 16 months, with lung function signs of mild obstruction. Assuming that a chance coexistence of cytomegalovirus pneumonia and Wilson-Mikity syndrome is rather unlikely, it is possible that intrauterine cytomegalovirus infection caused a pattern of lung injury consistent with Wilson-Mikity syndrome. Further cases of Wilson-Mikity syndrome should be investigated as to a possible role of congenital infection. (+info)
Qualitative and semiquantitative polymerase chain reaction testing for cytomegalovirus DNA in serum allows prediction of CMV related disease in liver transplant recipients.
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AIM: To identify cytomegalovirus (CMV) infection in liver transplant recipients by polymerase chain reaction (PCR) techniques and to separate the cases in which CMV related disease will occur, for whom treatment is indicated, from those in whom infection will remain innocuous. METHODS: The combination of qualitative and semiquantitative PCR of serum and urine was assessed to determine whether these assays can identify those at risk of CMV related disease and compared their performance with conventional approaches to diagnosis. RESULTS: Qualitative PCR of serum had superior specificity, sensitivity, and positive and negative predictive values compared with urine DEAFF (detection of early antigen fluorescent foci) and PCR of urine. All episodes of CMV related disease were associated with the presence of CMV DNA by PCR in serum or urine; CMV was detected before clinical onset in 70% and 60% of cases, respectively. The period over which CMV DNA could be detected was not correlated with CMV related disease. Both peak viral load and cumulative viral load estimated using a semiquantitative PCR method on serum samples positive by the qualitative method could be used to distinguish asymptomatic infection from CMV related disease with 100% specificity and sensitivity. In contrast semiquantitative PCR of urine was of little value. CONCLUSIONS: An approach based on PCR testing with a combination of qualitative and subsequently semiquantitative serum samples would improve the diagnosis of CMV infection and aid identification of those patients at risk of CMV related disease, allowing treatment to be targeted specifically. (+info)
Effects of human cytomegalovirus major immediate-early proteins in controlling the cell cycle and inhibiting apoptosis: studies with ts13 cells.
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The major immediate-early (MIE) gene of human cytomegalovirus (HCMV) encodes several MIE proteins (MIEPs) produced as a result of alternative splicing and polyadenylation of the primary transcript. Previously we demonstrated that the HCMV MIEPs expressed from the entire MIE gene could rescue the temperature-sensitive (ts) transcriptional defect in the ts13 cell line. This defect is caused by a ts mutation in TAFII250, the 250-kDa TATA binding protein-associated factor (TAF). These and other data suggested that the MIEPs perform a TAF-like function in complex with the basal transcription factor TFIID. In addition to the transcriptional defect, the ts mutation in ts13 cells results in a defect in cell cycle progression which ultimately leads to apoptosis. Since all of these defects can be rescued by wild-type TAFII250, we asked whether the MIEPs could rescue the cell cycle defect and/or affect the progression to apoptosis. We have found that the MIEPs, expressed from the entire MIE gene, do not rescue the cell cycle block in ts13 cells grown at the nonpermissive temperature. However, despite the maintenance of the cell cycle block, the ts13 cells which express the MIEPs are resistant to apoptosis. MIEP mutants, which have previously been shown to be defective in rescuing the ts transcriptional defect, maintained the ability to inhibit apoptosis. Hence, the MIEP functions which affect transcription appear to be separable from the functions which inhibit apoptosis. We discuss these data in the light of the HCMV life cycle and the possibility that the MIEPs promote cellular transformation by a "hit-and-run" mechanism. (+info)
Clinical significance of expression of human cytomegalovirus pp67 late transcript in heart, lung, and bone marrow transplant recipients as determined by nucleic acid sequence-based amplification.
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Human cytomegalovirus (HCMV) infection was monitored retrospectively by qualitative determination of pp67 mRNA (a late viral transcript) by nucleic acid sequence-based amplification (NASBA) in a series of 50 transplant recipients, including 26 solid-organ (11 heart and 15 lung) transplant recipients (SOTRs) and 24 bone marrow transplant recipients (BMTRs). NASBA results were compared with those obtained by prospective quantitation of HCMV viremia and antigenemia and retrospective quantitation of DNA in leukocytes (leukoDNAemia). On the whole, 29 patients were NASBA positive, whereas 10 were NASBA negative, and the blood of 11 patients remained HCMV negative. NASBA detected HCMV infection before quantitation of viremia did but after quantitation of leukoDNAemia and antigenemia did. In NASBA-positive blood samples, median levels of viremia, antigenemia, and leukoDNAemia were significantly higher than the relevant levels detected in NASBA-negative HCMV-positive blood samples. By using the quantitation of leukoDNAemia as the "gold standard," the analytical sensitivity (47.3%), as well as the negative predictive value (68. 3%), of NASBA for the diagnosis of HCMV infection intermediate between that of antigenemia quantitation (analytical sensitivity, 72. 3%) and that of viremia quantitation (analytical sensitivity, 28.7%), while the specificity and the positive predictive value were high (90 to 100%). However, with respect to the clinically relevant antigenemia cutoff of >/=100 used in this study for the initiation of preemptive therapy in SOTRs with reactivated HCMV infection, the clinical sensitivity of NASBA reached 100%, with a specificity of 68. 9%. Upon the initiation of antigenemia quantitation-guided treatment, the actual median antigenemia level was 158 (range, 124 to 580) in SOTRs who had reactivated infection and who presented with NASBA positivity 3.5 +/- 2.6 days in advance and 13.5 (range, 1 to 270) in the group that included BMTRs and SOTRs who had primary infection (in whom treatment was initiated upon the first confirmation of detection of HCMV in blood) and who presented with NASBA positivity 2.0 +/- 5.1 days later. Following antiviral treatment, the durations of the presence of antigenemia and pp67 mRNA in blood were found to be similar. In conclusion, monitoring of the expression of HCMV pp67 mRNA appears to be a promising, well-standardized tool for determination of the need for the initiation and termination of preemptive therapy. Its overall clinical impact should be analyzed in future prospective studies. (+info)
Multicenter comparison of the digene hybrid capture CMV DNA assay (version 2.0), the pp65 antigenemia assay, and cell culture for detection of cytomegalovirus viremia.
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We compared the Digene Hybrid Capture CMV DNA Assay version 2.0, the pp65 antigenemia assay, traditional tube culture, and shell vial culture for the detection of cytomegalovirus (CMV) viremia in several patient populations at three centers. Of 561 blood specimens collected from 402 patients, complete clinical and laboratory data were available for 489. Using consensus definitions for true positives and true negatives, the sensitivities of the Hybrid Capture assay, antigenemia, shell vial, and tube culture were 95, 94, 43, and 46%, respectively. The specificities of the Hybrid Capture assay and antigenemia were 95 and 94%, respectively. At all three study sites, the detected level of CMV viremia was significantly higher with the Hybrid Capture assay or antigenemia than with shell vial and tube culture. In a group of 131 healthy nonimmunosuppressed volunteers, the Hybrid Capture assay demonstrated a specificity of over 99%. The Hybrid Capture assay is a standardized assay that is simple to perform and can utilize whole blood specimens that have been stored for up to 48 h. The high sensitivity and specificity of the Hybrid Capture assay along with its simplicity and flexibility make it a clinically useful assay for the detection of CMV viremia in immunocompromised or immunosuppressed patients. Further evaluation to determine its role in predicting CMV disease and for monitoring the therapeutic response to anti-CMV therapy is needed. (+info)
Prior cytomegalovirus infection and the risk of restenosis after percutaneous transluminal coronary balloon angioplasty.
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BACKGROUND: Restenosis is a common problem after all revascularization procedures in atherosclerotic coronary arteries. Reactivated human cytomegalovirus (CMV) has been detected in tissues of restenotic vascular lesions and was hypothesized to be a contributing pathogenic factor. Recent data suggest an association of restenosis after optimal coronary atherectomy with CMV serostatus, and a possible role of antiviral therapy was discussed. We therefore tested the hypothesis that prior CMV infection might be a risk factor for restenosis after conventional coronary balloon angioplasty (PTCA). METHODS AND RESULTS: We analyzed 92 consecutive patients who had been admitted for control angiography after previous PTCA within a mean interval of 6 months. Anti-CMV antibodies were measured as an indicator of prior CMV infection and latency. The coronary angiograms before PTCA, directly after, and 6 months later were analyzed quantitatively. Sixty-five percent of the patients were CMV-positive. Before PTCA, the degree (mean+/-SD) of stenosis was 69+/-10% in CMV-positive and 68+/-8.3% in CMV-negative subjects. PTCA resulted in a residual stenosis of 39% in both groups. After 6 months, the late losses of luminal diameter in the CMV-positive and -negative groups were 11+/-13% and 12+/-15%, respectively (P=0.658). In an ANCOVA with 25 potential risk factors for restenosis, CMV serostatus was not significantly associated with restenosis development. CONCLUSIONS: Our data indicate that prior CMV infection, in contrast to optimal atherectomy, is not associated with chronic restenosis after conventional coronary balloon angioplasty. The results do not support a possible benefit from antiviral therapy. (+info)