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At least 19 recordsLinked to original sources

HIV and cytomegalovirus viral load and clinical outcomes in AIDS and cytomegalovirus retinitis patients: Monoclonal Antibody Cytomegalovirus Retinitis Trial.

OBJECTIVE: To determine the association of cytomegalovirus (CMV) viremia with mortality and CMV retinitis progression in newly diagnosed and relapsed CMV retinitis. DESIGN: Ancillary study of a randomized, placebo-controlled, phase III clinical trial. PATIENTS: A total of 83 patients with AIDS and CMV retinitis, enrolled during the first phase of the Monoclonal Antibody Cytomegalovirus Retinitis Trial, were administered MSL-109 or placebo as adjuvant therapy for CMV retinitis. MAIN OUTCOME MEASURE(S): Mortality and CMV retinitis progression. RESULTS: Treatment with MSL-109 did not predict either progression of CMV retinitis or mortality. Detection in plasma CMV DNA at baseline predicted mortality, but CMV antigenemia did not. CMV DNA was a better predictor of mortality than a high HIV viral load. Neither CMV DNA nor antigenemia predicted the progression of CMV retinitis. Among newly diagnosed patients, there was a decline in the proportion with detectable CMV viral load and CMV antigenemia in response to anti-CMV therapy. However, there was a rebound in CMV viral load to 25% and CMV antigenemia to 54.6% at 6 months. In relapsed patients, anti-CMV therapy was not associated with a change in the percentage with detectable CMV-DNA or CMV antigenemia over time. CONCLUSION: In patients with AIDS and CMV retinitis, the detection of plasma CMV DNA was associated with a higher risk of mortality than was a high HIV viral load. Anti-CMV therapy provided a transient reduction in CMV viremia in newly diagnosed but not relapsed patients with CMV retinitis. Adjuvant therapy with MSL-109 was ineffective in clearing CMV-DNA and CMV antigen from the plasma.

AIDS-Related Opportunistic Infections↗

[Immunity related to cytomegalovirus after allogenic bone marrow transplantation: role of donor immunity to cytomegalovirus in the incidence of cytomegalovirus infection in recipients].

Cytomegalovirus infections are severe and frequent after BMT. This study included 34 bone marrow transplant recipients (23 aplastic anaemias and 11 leukaemias), their marrow donors and 125 related or non related normal controls. Assays were performed before transplantation and every 30 days between D 0 and D 90, and then every six months. They included detection of CMV induced lymphocyte proliferation in vitro, CMV antibody determinations by complement fixation and reverse haemagglutination, viraemia and/or viruria. Similarly, cellular immunity to mitogens and to other specific antigens was evaluated. During the period of study, 22 patients developed CMV infection. The diagnostic was confirmed by virus isolation from the 12th to the 96th day after the graft. Development of positive CMV proliferation test occurred from the 9th to the 84th day after virus isolation (30 to 120th day after the graft). In one case, the CMV infection was only proved by the lymphocyte proliferation to CMV in vitro and only 60 days later by viruria and 105 days later by detection of CMV antibodies. For the other 12 patients (7 aplasies and 5 leukaemias) and 10 of their bone marrow donors, no CMV infection was proved, before or after transplant, by any of the assays performed. By selecting a donor without previous CMV infection, we hope to reduce the incidence of CM infection in recipients.

Anemia, Aplastic↗

Cytomegalovirus excretion as a predictor of cytomegalovirus disease after marrow transplantation: importance of cytomegalovirus viremia.

Cytomegalovirus (CMV) viremia and excretion from the oropharynx and urine were examined for their utility in predicting the development of CMV disease, including pneumonia and gastrointestinal disease, among 617 marrow allograft recipients. CMV viremia had a 60% and excretion from oropharynx or urine or viremia a 44% positive predictive value for the development of CMV disease. Viremia or excretion preceded disease onset by a median of 15 days among those in whom excretion occurred first. In stepwise time-dependent proportional hazards regression analyses, CMV viremia and positive serology before transplant were predictive for both CMV pneumonia and gastrointestinal disease. Oropharyngeal excretion was independently predictive for gastrointestinal disease but not pneumonia. Urinary excretion was not independently predictive. Acute graft-versus-host disease was predictive for pneumonia but not gastrointestinal disease. Thus use of CMV excretion, particularly viremia, as a marker to determine the initiation of antiviral chemotherapy could be effective in preventing progression of infection to serious disease. However, with standard virologic techniques this strategy would not be effective in patients (32% in this study) without CMV excretion detected before the onset of pneumonia or gastrointestinal disease.

Adolescent↗

Quantitative measurement of cytomegalovirus-specific IgG and IgM antibodies in relation to cytomegalovirus antigenaemia and disease activity in kidney recipients with an active cytomegalovirus infection.

In a longitudinal investigation 103 kidney recipients were studied with respect to the development of cytomegalovirus (CMV) specific antibodies of the IgG and IgM class, in relation to the detection of CMV antigenaemia (immediate early antigen, IEA), in weekly obtained blood samples during the first 3 months after transplantation. In 15 out of 49 (31%) seronegative patients a primary infection occurred, which was characterized by a quick rise in IgM antibody followed by a slower production of IgG antibody, high maximum numbers of IEA+ cells, and a CMV syndrome in 11 patients. In 35 out of 54 (65%) seropositive patients a secondary infection occurred. After a post-operative fall in the IgG antibody, which was also found in patients without an active infection and which was accompanied by a similar drop in serum albumin and IgG, a second dip in IgG antibody was found 6 days before the first IEA+ leucocyte appeared in the blood. This was followed by a significant increase, indicative of an active immune response in consequence of the infection, 18 days later. In 31 of these 35 patients an IgM response was found. This could be ascribed to the presence of rheumatoid factor activity in 20 of them. Eight patients who showed a transient rise in IgG antibody between the two dips could be distinguished from the remaining ones by a lower maximum number of IEA+ cells and less severe disease symptoms. The described results suggest that (i) an adequate humoral immune system may prevent symptomatic CMV disease in secondary infections; and (ii) CMV-specific antibodies may be removed from the circulation by antigens present in infected tissues before CMV antigenaemia becomes detectable.

Antibodies, Viral↗

Comparison of cytomegalovirus loads in plasma and leukocytes of patients with cytomegalovirus retinitis. The Cytomegalovirus Retinitis and Viral Resistance Study Group.

Cytomegalovirus (CMV) DNA loads in paired leukocyte and plasma samples from 199 patient visits by 66 patients with CMV retinitis were determined. Leukocyte CMV load determinations had a greater range of values (mean, 24,587 copies/10(6) leukocytes; maximum, 539, 000) than did plasma CMV load determinations (mean, 10,302 copies/ml; maximum, 386,000), and leukocyte viral loads were detectable in a greater proportion of patients at the time of diagnosis of CMV retinitis prior to initiation of anti-CMV therapy (82%) than were plasma viral loads (64%) (P = 0.0078). Agreement with CMV blood cultures was slightly better for plasma (kappa = 0. 68) than for leukocytes (kappa = 0.53), due to a greater proportion of patients with detectable viral loads in leukocytes having negative blood cultures.

Cytomegalovirus↗

Cytomegalovirus-specific lymphocyte proliferation and in vitro cytomegalovirus IgG synthesis for diagnosis of cytomegalovirus infections after bone marrow transplantation.

With new techniques 19 bone marrow transplant (BMT) recipients were monitored for lymphocyte proliferation and specific IgG production in vitro by cytomegalovirus (CMV) antigen in solid phase. Twelve patients got a reactivated CMV infection as defined by virus isolation or serum IgG conversion. Lymphocyte proliferation and in vitro IgG production responses were significantly stronger in these 12 patients than in seven without ongoing CMV infection (P = .02). CMV infection was indicated by the lymphocyte responses at a mean of 45 days after BMT as against a mean of 79 days that passed before CMV growth in culture was detected (P less than .05). Lymphocyte proliferation and in vitro IgG production may thus be used as tools for diagnosis and for monitoring of CMV infections in BMT recipients.

Adolescent↗

Randomized controlled trial of sequential intravenous and oral ganciclovir versus prolonged intravenous ganciclovir for long-term prophylaxis of cytomegalovirus disease in high-risk cytomegalovirus-seronegative liver transplant recipients with cytomegalovirus-seropositive donors.

Cytomegalovirus (CMV)-seronegative liver transplant recipients with CMV-seropositive donors have the greatest risk for CMV disease. We performed a randomized, controlled trial comparing sequential intravenous (IV) and oral ganciclovir with prolonged IV ganciclovir for long-term prophylaxis of CMV disease in these high-risk patients. Patients were initially given IV ganciclovir at a dose of 6 mg/kg per day from days 1 to 14 after transplantation. Patients then either received oral ganciclovir (1 g every 8 hr) or continued IV ganciclovir (6 mg/kg once per day on Monday-Friday of each week) from days 15 to 100 after transplantation. CMV disease occurred in 3 of 32 patients (9.3%) receiving oral ganciclovir and in 4 of 32 patients (12.5%) receiving IV ganciclovir within the first year after transplantation (P>0.2). All cases of CMV disease occurred more than 90 days after transplantation (median time of onset day +137 for oral ganciclovir and day +135 for IV ganciclovir). There were no deaths from CMV in either study group. Both oral and IV ganciclovir were generally well tolerated. These results indicate that, after induction with 14 days of IV ganciclovir, oral ganciclovir can be as effective as IV ganciclovir for long-term prophylaxis of CMV disease in high-risk CMV-seronegative liver transplant recipients with CMV-seropositive donors and eliminates the need for prolonged IV access.

Administration, Oral↗

Cytomegalovirus-specific IFN-gamma production is associated with protection against cytomegalovirus reactivation in HIV-infected patients on highly active antiretroviral therapy.

OBJECTIVES: To identify the predictors of cytomegalovirus reactivation in AIDS patients on highly active antiretroviral therapy (HAART). DESIGN: This prospective study enrolled cytomegalovirus-seropositive AIDS patients on or about to start HAART, who were not receiving anti-cytomegalovirus prophylaxis. Clinical and laboratory data were collected over 3.5 years at clinic visits, which coincided with the study visits. METHODS: Blood was obtained at every study visit and was used for measurements of cytomegalovirus cell-mediated immunity (lymphocyte proliferation, IFN-gamma, IL-2, and IL-10 production), cytomegalovirus viral load, CD4 cell count, and HIV viral load. A logistic-normal model was used to analyse outcome data with repeated observations. RESULTS: Twenty-six patients had 40 episodes of cytomegalovirus reactivation (positive cytomegalovirus viral load) during the study. Their immunological and virological parameters were compared with 26 randomly selected control individuals from the same cohort. The risk of cytomegalovirus reactivation significantly decreased with every 6-month increase in HAART duration [odds ratio (OR) 0.5; P = 0.02] and marginally increased with every log10 RNA copies/ml HIV viral load (OR 2; P = 0.07). CD4 cell counts, cytomegalovirus lymphocyte proliferation, IL-2, and IL-10 did not reach significance as predictors of cytomegalovirus reactivation. However, cytomegalovirus IFN-gamma production significantly decreased the risk of cytomegalovirus reactivation (OR 0.03; P = 0.04). CONCLUSION: Cytomegalovirus-specific IFN-gamma has a unique value as an immunological predictor of cytomegalovirus reactivation, demonstrating the importance of cellular immune responses in the control of cytomegalovirus replication in HAART recipients.

Adult↗

Monitoring of cytomegalovirus disease after heart transplantation: persistence of anti-cytomegalovirus IgM antibodies.

During the first year after orthotopic heart transplantation 39 recipients (given prophylactic immunosuppression with antithymocyte globulin for 7 days after orthotopic heart transplantation and triple drug maintenance therapy) were screened for cytomegalovirus antigenemia and anti-cytomegalovirus immunoglobulin M (index) and immunoglobulin G levels (antibody units) by MEIA-method. Until day 14, all recipients received cytomegalovirus hyperimmunoglobulin at a dosage of 2 ml/kg/day. Four patient groups were defined: group 1 (n = 15) seropositive recipient/seropositive donor, group 2 (n = 9) seronegative recipient/seropositive donor, group 3 (n = 8) seropositive recipient/seronegative donor and group 4 (n = 7) seronegative recipient/seronegative donor. Twenty-four donors and 23 recipients were seropositive for anti-cytomegalovirus immunoglobulin G. After transplantation, 31 recipients tested positive for cytomegalovirus antigenemia before immunoglobulin M elevation and at least 7 days before the onset of clinical symptoms of cytomegalovirus. In group 2, episodes of cytomegalovirus antigenemia appeared earlier, were more frequent, and lasted longer than in groups 1 and 3. Without previous evidence of positive cytomegalovirus antigenemia testing, no sign of cytomegalovirus disease was seen. When cytomegalovirus antigenemia was positive, cytomegalovirus hyperimmunoglobulin was readministered at the same dosage and gancyclovir (1000 mg/day) was given until cytomegalovirus antigenemia disappeared. However, episodes of recurrent cytomegalovirus were observed (2.6 +/- 1.9, 4.3 +/- 1.0, and 2.3 +/- 1.2 in groups 1, 2 and 3, respectively). In groups 1 and 3, the anti-cytomegalovirus immunoglobulin G antibody level remained high during the observation period. In groups 2 and 4 anti-cytomegalovirus immunoglobulin G antibodies were positive because of hyperimmunoglobulin prophylaxis but immunoglobulin G decreased again after discontinuation of the prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗

Determination of cytomegalovirus DNA load for monitoring of cytomegalovirus disease and antiviral treatment in solid organ transplant patients, comparing limiting-dilution PCR and hybrid capture assay with cytomegalovirus isolation.

OBJECTIVE: To improve the identification of patients at risk of developing cytomegalovirus (CMV) disease. MATERIALS AND METHODS: In a prospective study of 50 kidney or liver transplant patients who developed fever, 133 EDTA blood samples were analyzed, using two tests to measure CMV DNA: a 10-fold limiting dilution of an extract of 2 million leukocytes for CMV PCR, and a CMV hybrid capture assay. Both tests were compared with virus isolation, using an equivalent amount of leukocytes as a base for all three tests. RESULTS: The limiting-dilution CMV PCR and the hybrid capture assay presented relatively similar changes of sensitivity and specificity at different CMV DNA concentrations. The kinetics of the positive and negative predictive values were also comparable. A higher CMV DNA load corresponded to an increased risk of developing CMV disease. Furthermore, an increase in the endpoint dilution of a positive CMV PCR also corresponded to more severe disease. After antiviral treatment, the CMV PCR decreased by at least 100-fold (2 log10) in 10 cases and by 10-fold (1 log10) in five cases. Thus, there was a decrease in 15 of 18 (83%) patients. Similarly, with the hybrid capture assay, the amount of CMV DNA decreased about 100-fold in five patients and decreased by about 0.5 genome equivalents in five cases, i.e. in 10 of 12 (83%) patients. CONCLUSION: Both methods proved clinically useful for detecting patients at risk of developing CMV disease and for monitoring antiviral treatment in solid organ transplant patients.

Journal Article↗

Cytomegalovirus-specific B cell activation as a potential marker for the diagnosis of cytomegalovirus infection.

In vitro secretion of antibodies to cytomegalovirus was investigated by analysis of peripheral blood mononuclear cell culture supernatants from subjects infected with cytomegalovirus. Patients with primary or recurrent cytomegalovirus infection showed transient in vitro cytomegalovirus-specific antibody secretion. A high proportion of patients infected with human immunodeficiency virus and sero-positive for cytomegalovirus showed in vitro cytomegalovirus-specific antibody secretion. All peripheral blood mononuclear cell cultures from patients with symptomatic human immunodeficiency virus infection were found to secrete in vitro antibodies to cytomegalovirus, despite the fact that isolation of cytomegalovirus from some of these patients was not achieved. In human immunodeficiency virus-infected patients, in vitro secretion of anti-cytomegalovirus antibodies appeared to be persistent. In vitro cytomegalovirus-specific antibody secretion by peripheral blood lymphocytes probably reflects an in vitro cytomegalovirus-specific B cell activation. This new assay could be considered an interesting method for detecting both acute or chronic cytomegalovirus infection, with potential use in routine laboratory practice.

Adult↗

Cytomegalovirus resistance to ganciclovir and clinical outcomes of patients with cytomegalovirus retinitis.

PURPOSE: To evaluate whether cytomegalovirus resistant to ganciclovir, detected in either the blood or urine, correlates with adverse ocular outcomes. DESIGN: Prospective cohort study. METHODS: Patients with cytomegalovirus and AIDS were enrolled in a study of the occurrence and clinical correlates of resistant cytomegalovirus. Blood and urine cultures for cytomegalovirus were performed at the time of diagnosis of retinitis, 1 and 3 months after the initiation of therapy, and every 3 months thereafter. Patients were seen monthly, at which time fundus photographs were obtained and forwarded to the Fundus Photograph Reading Center for evaluation of retinitis progression (movement of a border of a cytomegalovirus lesion > or = 750 microm, or the occurrence of a new lesion > or = 0.25 disk area in size) and the amount of retinal area affected by cytomegalovirus retinitis. Visual acuity was measured using logarithmic visual acuity charts. Phenotypic resistance to ganciclovir was defined as an IC50 > 6.0 micromol/l, and genotypic resistance to ganciclovir was defined as the occurrence of a cytomegalovirus UL97 gene mutation known to confer ganciclovir resistance. Time-dependent analyses were performed and included viral resistance, highly active antiretroviral therapy, and treatment variables as predictors of clinical outcomes. RESULTS: One hundred ninety-seven patients received ganciclovir therapy. Nineteen patients developed phenotypic resistance to ganciclovir, and 18 developed genotypic resistance. The detection of cytomegalovirus resistant to ganciclovir was associated with a 4.17- to 5.61-fold increase in the odds of retinitis progression (P values all < or = .0002), depending upon the definition of resistance and the culture sources analyzed. Resistance was associated with a greater increase in retinal area involved by cytomegalovirus by 3-month interval (1.10% vs 0.05% to 0.10%), which was significant for phenotypic resistance and for genotypic resistance in the blood or urine (P =.012 to.021). There was a suggestion that resistance was associated with a greater loss of visual acuity (P =.009 to.096). Highly active antiretroviral therapy was associated with an approximate 50% reduction in the odds of retinitis progression, and the ganciclovir implant was associated with an approximate 60% reduction. CONCLUSIONS: The detection of cytomegalovirus resistant to ganciclovir in either the blood or urine of a patient with cytomegalovirus retinitis is associated with an increased risk of adverse ocular outcomes.

AIDS-Related Opportunistic Infections↗

Preemptive ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus antibody-positive renal transplant recipients. A randomized controlled trial.

OBJECTIVE: To determine whether preemptive ganciclovir therapy administered daily during antilymphocyte antibody therapy can prevent cytomegalovirus disease in renal transplant recipients who are positive for cytomegalovirus antibody. DESIGN: Randomized, controlled, multicenter trial. SETTING: 6 university-affiliated transplantation centers. PATIENTS: 113 renal transplant recipients who were positive for cytomegalovirus antibody. INTERVENTION: Patients were randomly assigned to receive either 1) ganciclovir, 2.5 mg/kg body weight administered intravenously on every day that antilymphocyte antibody therapy was administered or 2) no anticytomegalovirus therapy. MEASUREMENTS: Patients were observed for 6 months after completion of antilymphocyte antibody therapy for development of cytomegalovirus disease and cytomegalovirus viremia. RESULTS: Cytomegalovirus disease occurred in 14% of patients (9 of 64) who received preemptive ganciclovir therapy and in 33% of controls (16 of 49) (P = 0.018). Cytomegalovirus was isolated from buffy-coat specimens from 17% of patients (11 of 64) receiving preemptive ganciclovir and from 35% of controls (17 of 49) (P = 0.03). Controlling for the reason (induction or treatment of rejection) for using antilymphocyte antibodies in a Cox proportional hazards model, we found that preemptive ganciclovir still protected against cytomegalovirus disease (adjusted relative risk, 0.27; 95% CI, 0.12 to 0.64). No adverse events were attributed to preemptive ganciclovir therapy during or within 6 months of its administration. CONCLUSIONS: Preemptive ganciclovir therapy administered daily during courses of treatment with antilymphocyte antibodies reduced the excessive occurrence of cytomegalovirus disease in renal transplant recipients who were positive for cytomegalovirus antibody. This approach, which links the most potent immunosuppression to intensive antimicrobial therapy, allows preventive therapy to be given to those patients at greatest risk for developing infectious complications. These patients are likely to benefit most from the preventive strategy.

Adolescent↗

Detection of cytomegalovirus in paraffin-embedded postmortem coronary artery specimens of heart transplant recipients by the polymerase chain reaction: implications of cytomegalovirus association with graft atherosclerosis.

To assess the presence of cytomegalovirus in various tissues and its relevance to the development of graft atherosclerosis, 54 postmortem paraffin-embedded tissue samples from 15 heart transplant recipients who survived more than 100 days were analyzed by the polymerase chain reaction for cytomegalovirus. Eight patients had known previous cytomegalovirus exposure; 7 patients did not. Of the eight with known previous exposure, three patients (38%) died of graft atherosclerosis versus four (57%) of the seven patients without previous exposure. Of the 54 specimens, 49 were positive for beta-globin (inclusive positive control), including 38 coronary artery, five lung, five gastrointestinal, and one kidney. Only two coronary artery specimens were cytomegalovirus positive in a single patient with known cytomegalovirus exposure who did not have evidence of graft atherosclerosis at autopsy. Other tissues tested showed positive lung and stomach specimens in the patient with cytomegalovirus-positive coronary artery specimens and positive kidney, lung, and gastrointestinal specimens in a second patient. No specimens were cytomegalovirus positive in the remaining patients, despite the presence of graft atherosclerosis or previous cytomegalovirus exposure. Our data do not support the hypothesis that graft atherosclerosis is associated with latent cytomegalovirus infection of the coronary arteries. The role of cytomegalovirus in the pathogenesis of graft atherosclerosis is unknown, but possibly it represents a modulation of the immune system by remote infection.

Adolescent↗

Longitudinal observations on mutations conferring ganciclovir resistance in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis: The Cytomegalovirus and Viral Resistance Study Group Report Number 8.

PURPOSE: Cytomegalovirus retinitis is the most common intraocular infection in patients with acquired immunodeficiency syndrome (AIDS). With prolonged suppressive anticytomegalovirus maintenance therapy, resistance occurs in over 25% of patients. We evaluated longitudinal changes in the cytomegalovirus genotype in patients with cytomegalovirus retinitis who developed ganciclovir resistance that was demonstrated in either the blood or urine. METHODS: Patients with AIDS and previously untreated cytomegalovirus retinitis were followed prospectively for the occurrence of resistance while on treatment. Blood and urine specimens were obtained periodically for cytomegalovirus culture according to a predetermined schedule. Positive isolates were tested for phenotypic susceptibility and for mutations in the UL97 and UL54 genes. RESULTS: A mutation conferring resistance to ganciclovir in either the UL97 or UL54 gene was detected in 18 patients. In general, patients with a genotypically resistant virus developed increasing phenotypic resistance over time. There was a suggestion that unless therapy was changed, UL97 mutations tended to persist. In seven of eight patients, the mutations identified in isolates from the blood and urine were identical. In selected patients, there was a suggestion that a mixed population of cytomegalovirus might be present. Progression of the retinitis in an involved eye (15 of 18), contralateral eye retinitis (10 of 11), and extraocular cytomegalovirus disease (5 of 18) occurred commonly among patients with resistant virus. CONCLUSION: Resistance-conferring mutations in the cytomegalovirus genome emerge and may persist when the selective pressure for resistance is maintained. Some patients appear to harbor complex subpopulations of virus with different mutations and different levels of phenotypic resistance. Changes in therapy may result in a shift in virus population and changes in the cytomegalovirus genotype identified.

AIDS-Related Opportunistic Infections↗

Cytomegalovirus immune globulin and seronegative blood products to prevent primary cytomegalovirus infection after marrow transplantation.

In an attempt to prevent primary cytomegalovirus infection after marrow transplantation, we randomly assigned 97 patients who were seronegative for antibody to cytomegalovirus before transplantation to receive one of the following: (1) both intravenous cytomegalovirus immune globulin and seronegative blood products (23 patients); (2) seronegative blood products alone (28 patients); (3) globulin alone (22 patients); or (4) neither treatment (24 patients). Patients not assigned to receive seronegative blood products received unscreened blood products from random donors. The incidence of cytomegalovirus infection according to study group among patients in the study for at least 62 days was 5 percent, 13 percent, 24 percent, and 40 percent, respectively. Among 57 patients with seronegative marrow donors, those who received seronegative blood products had significantly less infection (1 of 32) than those who received standard blood products (8 of 25, P less than 0.007). In contrast, the use of seronegative blood products did not appear to prevent cytomegalovirus infection among patients with seropositive marrow donors. The possibility that cytomegalovirus immune globulin as used in this study can prevent cytomegalovirus infection or ameliorate cytomegalovirus disease was not confirmed, and it cannot be recommended for routine use without additional study.

Adolescent↗

Detection of human cytomegalovirus DNA in liver biopsies from patients with cytomegalovirus-related liver disease.

Infection with human cytomegalovirus (HCMV) has been associated with severe diseases in immunologically impaired patients. Cytomegalovirus hepatitis has been frequently described in this population, but this diagnosis is still difficult. Molecular hybridization with the V EcoRI restriction fragment of human cytomegalovirus strain AD 169 has been tested upon DNA extracted from liver samples to assess the usefulness of this technique for cytomegalovirus hepatitis diagnosis. This probe was shown by the Southern technique not to hybridize with DNA extracted from cells infected with other herpesviruses or with DNA of non-infected normal liver. The sensitivity was estimated to be 2 x 10(5) genomes. Twenty-five renal transplant recipients under immunosuppressive therapy and three patients having the acquired immunodeficiency syndrome were studied. In 9 out of 10 renal transplant recipients with normal liver, previous exposure to cytomegalovirus, as defined by serological tests, was not sufficient to allow positive detection by the probe. Out of 11 patients with abnormal liver, cytomegalovirus DNA sequences were shown in 5. In 2 patients with histological evidence of cytomegalovirus hepatitis, a very strong signal showed the presence of viral genomes. These results show that the Southern technique with the V EcoRI probe can be useful for the diagnosis of HCMV hepatitis and might be proposed for the detection of this viral genome in human tissues.

Acquired Immunodeficiency Syndrome↗

Treatment of cytomegalovirus pneumonia after bone marrow transplantation with cytomegalovirus immunoglobulin combined with ganciclovir.

We studied the effect of cytomegalovirus immunoglobulin alone, or combined with ganciclovir, on the outcome of biopsy proven cytomegalovirus pneumonia after bone marrow transplantation. Treatment with cytomegalovirus immunoglobulin alone had no effect on the cytomegalovirus nor on clinical outcome. The combined treatment of cytomegalovirus immunoglobulin with ganciclovir suppressed the cytomegalovirus but all patients died because of ongoing pulmonary deterioration. These results may suggest that this combined treatment has limited value on the outcome of an established cytomegalovirus pneumonia after marrow transplantation.

Acyclovir↗