RESUMO
BACKGROUND: Bone marrow transplant (BMT) patients at risk of developing cytomegalovirus (CMV) pneumonitis are identified routinely by the early detection of virus in blood. For early diagnosis of CMV infection, the RNA-based approach demonstrates advantages when compared with the current CMV antigen and DNA detection methods. OBJECTIVES: We have evaluated our previously developed reverse transcription-polymerase chain reaction (RT-PCR) to a spliced late CMV gene (SLG; J. Virol. Methods 56 (1996), 139) to monitor CMV infection in BMT patients at two clinical sites. The diagnostic value of the SLG RT-PCR was compared with the routine CMV antigen and DNA detection methods. STUDY DESIGN: Weekly blood samples from BMT patients were tested for CMV during the first 3 months post-transplant. The qualitative SLG RT-PCR, semiquantitative DNA PCR, and viral antigen tests were compared. The RNA and DNA PCR results were analysed in terms of their temporal relationship and consistency of CMV detection and compared with CMV infection diagnosed by viral antigen tests. RESULTS: Of the 101 BMT recipients studied, 25 developed CMV antigenemia and/or DNAemia resulting in symptomatic infection in two patients. All CMV PCR-positive patients were either CMV seropositive pretransplant or received marrow from seropositive donor. The highest incidence of CMV infection was seen in seropositive recipients (R+) irrespective of the donor's status. Detection of CMV infection by SLG RNA preceded CMV DNA detection by 0-2 weeks (median 1 week) and CMV antigen detection by 0-8 weeks (median 3 weeks). Once detected, the SLG RNA remained consistently positive before antiviral treatment was commenced. Both the SLG RNA and CMV DNA detection methods had the same clinical sensitivity, specificity, positive and negative predictive values of 100, 94, 80 and 100%, respectively. CONCLUSIONS: The RT-PCR for SLG RNA proved to be the earliest indicator of CMV infection in BMT patients demonstrating a sustained pattern of CMV detection during the 3 months post-transplant period. Although very similar in its diagnostic performance to CMV DNA PCR the SLG RNA RT-PCR does not require quantitation and provides an efficient and ongoing indication of active CMV infection.
Assuntos
Transplante de Medula Óssea , Infecções por Citomegalovirus/etiologia , Citomegalovirus/isolamento & purificação , Complicações Pós-Operatórias , Adolescente , Antígenos Virais/análise , Citomegalovirus/genética , Citomegalovirus/imunologia , DNA Viral/análise , Humanos , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Carga ViralRESUMO
A recent post-marketing study indicated that high doses of standardised artichoke leaf extract (ALE) may reduce symptoms of dyspepsia. To substantial these findings, this study investigated the efficacy of a low-dose ALE on amelioration of dyspeptic symptoms and improvement of quality of life. The study was an open, dose-ranging postal study. Healthy patients with self-reported dyspepsia were recruited through the media. The Nepean Dyspepsia Index and the State-Trait Anxiety Inventory were completed at baseline and after 2 months of treatment with ALE, which was randomly allocated to volunteers as 320 or 640 mg daily. Of the 516 participants, 454 completed the study. In both dosage groups, compared with baseline, there was a significant reduction of all dyspeptic symptoms, with an average reduction of 40% in global dyspepsia score. However, there were no differences in the primary outcome measures between the two groups, although relief of state anxiety, a secondary outcome, was greater with the higher dosage (P = 0.03). Health-related quality of life was significantly improved in both groups compared with baseline. We conclude that ALE shows promise to ameliorate upper gastro-intestinal symptoms and improve quality of life in otherwise healthy subjects suffering from dyspepsia.
Assuntos
Colagogos e Coleréticos/uso terapêutico , Dispepsia/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Colagogos e Coleréticos/administração & dosagem , Dispepsia/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Extratos Vegetais/administração & dosagem , Folhas de Planta , Vigilância de Produtos Comercializados , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do TratamentoRESUMO
The management of jaundice in patients with primary sclerosing cholangitis (PSC) is clinically challenging. In patients in whom the recognized precipitants for jaundice have been excluded, the outlook is uncertain at best. Some improve spontaneously, but the only treatment demonstrated to be effective is liver transplantation--which may not always be appropriate. We report three cases of jaundice in patients with PSC in whom corticosteroid therapy appeared to be beneficial.
Assuntos
Colangite Esclerosante/complicações , Icterícia/tratamento farmacológico , Icterícia/etiologia , Prednisolona/administração & dosagem , Administração Oral , Idoso , Análise Química do Sangue , Colangite Esclerosante/diagnóstico , Esquema de Medicação , Feminino , Seguimentos , Humanos , Icterícia/diagnóstico , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Antivirais/uso terapêutico , Hepacivirus , Hepatite C/terapia , Imunoterapia , Antivirais/economia , Carcinoma Hepatocelular/virologia , Análise Custo-Benefício , Feminino , Genes Virais , Hepacivirus/genética , Hepatite C/epidemiologia , Hepatite C/etiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/terapia , Humanos , Interferon-alfa/efeitos adversos , Interferon-alfa/economia , Interferon-alfa/uso terapêutico , Neoplasias Hepáticas/virologia , Masculino , Reação em Cadeia da Polimerase , Prevalência , Prognóstico , RecidivaRESUMO
Human cytomegalovirus (CMV) is a major cause of morbidity in heart and lung transplant patients, resulting from immunosuppression-mediated reactivation of latent CMV originating either from the transplanted tissue, or the recipient. We showed that out of eight donor/recipient pairs, the lymph nodes (LNs) of three donors and four recipients, all CMV seropositive, harboured CMV DNA at exceeding levels compared with those of matched blood samples, as well as CMV RNA otherwise undetectable in patients' blood. On follow-up, patients positive for CMV DNA and RNA in LNs developed viraemia 4 to 5 weeks earlier than those initially polymerase chain reaction-negative for CMV. Our results indicate that LN are a significant site for sequestration and persistence of CMV and that LN may be important in seeding of CMV-infected cells into the circulation.
Assuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus/isolamento & purificação , DNA Viral/análise , Transplante de Coração , Transplante de Pulmão , Linfonodos/virologia , Doadores de Tecidos , Citomegalovirus/genética , DNA Viral/sangue , Genoma Viral , Humanos , Reação em Cadeia da Polimerase , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , ViremiaRESUMO
Polymerase chain reaction using specific primers, failed to detect HTLV-I amplicons in patients with rheumatic diseases previously shown to possess antibodies to retroviral products. However, by employing broad spectrum oligonucleotide primers, 135 bp amplicons were generated from peripheral blood mononuclear cells and synovial fluid cells. Subsequent cloning and DNA sequencing revealed homology to a number of exogenous and human endogenous retroviruses (HERVs). Furthermore, in combining the presence of type B and C related endogenous retroviruses, a significant association (p=0.014) was apparent for chronic autoimmune rheumatic diseases as compared to controls. Reverse transcription polymerase chain reaction of RNA derived from patients, healthy controls and cell lines (U937, BJAB, human endothelial lung fibroblasts) demonstrated ubiquitous expression of HERV-K10 and RTVL-H2. Furthermore messenger RNA expression of HERV-K10 was enhanced in fibroblasts infected with human cytomegalovirus. It is plausible that subsequent production of HERV peptides could explain the presence of anti-retroviral antibodies in cohorts of patients with autoimmune rheumatic diseases.
Assuntos
Anticorpos Antivirais/sangue , Doenças Autoimunes/etiologia , Retrovirus Endógenos/imunologia , Doenças Reumáticas/etiologia , Linhagem Celular , DNA Complementar/genética , Retrovirus Endógenos/genética , Retrovirus Endógenos/fisiologia , Humanos , Reação em Cadeia da Polimerase , RNA Viral/genética , RNA Viral/isolamento & purificação , Análise de Sequência de DNARESUMO
Hepatitis C virus (HCV) genotype 4 is believed to be predominant in the Middle East including Saudi Arabia (SA). We attempted to genotype 80 HCV isolates from different parts of SA by direct sequencing of a variable 222bp fragment from the NS5B region. The phylogenetic analysis of the NS5B sequences was complemented by direct sequence analysis of the conserved 5'-NCR region for HCV type-specific polymorphism. All 80 NS5B sequences separated into 3 clades which comprised 6 type 1b variants, 30 type 4 variants (24 of type 4a and 6 of type 4c or d) and 44 type 3 variants. Apart from two definitive type 3b variants the other 42 type 3 NS5B sequences formed 4 clusters with low similarity to type 3a-f HCV sequences from the database. The precise subtyping of these 42 type 3 variants awaits sequencing of longer HCV RNA stretches. Our results indicate that HCV type 4 may not be the only dominant genotype in SA.
Assuntos
Hepacivirus/genética , Hepatite C/virologia , Doenças Endêmicas , Genótipo , Hepacivirus/classificação , Humanos , Epidemiologia Molecular , Filogenia , Polimorfismo Genético , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Arábia Saudita/epidemiologia , Análise de Sequência de DNA , Proteínas não Estruturais Virais/genéticaRESUMO
OBJECTIVE: A one year study of the relation between cytomegalovirus (CMV) and human immunodeficiency virus (HIV) viral loads in a cohort of children with vertically acquired HIV-1 infection. DESIGN: Comparative analysis of viral load measurements for CMV and HIV-1 in peripheral blood leucocytes (PBLs) of individual children in relation to age and clinical staging. METHODS: Nested polymerase chain reaction (PCR) was used to measure HIV-1 proviral DNA and CMV genomic DNA in PBLs of 56 children. RESULTS: The CMV load was highest in 0-2 year old HIV positive children with stage C disease (range, 1-7143 copies/100 ng DNA; median, 125) and was significantly lower in older children. Although higher in young children, HIV-1 viral load did not show the same marked reduction with age that is seen with CMV. Over a one year period, testing of serial samples for both viruses in a subgroup of children revealed a discordant relation between viral loads for CMV and HIV-1. CONCLUSIONS: CMV viral load falls much faster than HIV viral load in dually infected children. Screening for clinical CMV disease is most likely to be of benefit in children under 2 years of age with stage C disease. In the few children studied, levels of CMV and HIV replication appear to be independent.
Assuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus , Infecções por HIV/virologia , HIV-1 , Carga Viral , Adolescente , Fatores Etários , Criança , Pré-Escolar , Infecções por Citomegalovirus/complicações , DNA Viral/sangue , Infecções por HIV/complicações , Humanos , Lactente , Estudos Longitudinais , Reação em Cadeia da Polimerase/métodos , Fatores de TempoRESUMO
To investigate the generation of an abnormally long HIV-1 env PCR DNA product the latter was cloned and sequenced followed by sequence analysis of HIV-1 primer binding sites. We found that the formation of an abnormally long PCR product was due to HIV-1 env sequence alteration (a) in the reverse primer binding site resulting in faulty primer binding and (b) downstream from the forward primer sequence resulting in a new binding site with reverse complementary sequence with respect to the forward primer at the opposite end of the PCR product. Both changes led to amplification of a longer PCR product with forward primer alone. Our results indicate that the HIV-1 genetic diversity in the env gene can lead to amplification of a specific PCR product of unexpected size which can be disregarded in the absence of its cross-validation.
Assuntos
Produtos do Gene env/genética , HIV-1/genética , Adolescente , Sequência de Bases , Sítios de Ligação/genética , Criança , Pré-Escolar , Genes Virais , Variação Genética , HIV-1/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Reação em Cadeia da Polimerase/métodos , Sensibilidade e EspecificidadeRESUMO
The development of secure diagnostic immunoassays requires, among others, rigorous characterisation of potential antibody reagents. The reactivity profiles of seven antibodies (six monoclonal [MAb] and one polyclonal [PAb]) with putative specificity for tartrate-resistant acid phosphatase (TRAP) and/or osteoclasts were evaluated in enzyme-linked immunosorbent assay (ELISA) and/or immunocytochemistry. MAbs 2H1, 4E6 and 5Cl demonstrated assay restriction: exhibiting reactivity only in ELISA. The remaining three MAbs (G211D, G312G and V35B) and the PAb 8023 recognised recombinant TRAP (rTRAP) in ELISA and native acid phosphatases in selected tissues and cell lines. The latter were cytochemically assessed for both tartrate-sensitive acid phosphatase (TSAP) and TRAP. V35B showed reactivity against the monocytic leukaemia cell line U937 and guinea pig kidney tissue (both TSAP+ and TRAP+) and ECV304 (TSAP+) cells. Interestingly, the reactivity of MAb G211D co-localised with TRAP activity in the membrane of osteoclasts but also detected cytoplasmic components in U937 cells and human embryonic lung fibroblasts (TRAP+ and TRAP+). G211D exhibited immunoreactivity against placental trophoblasts (positive for total AP). Intriguingly, MAbs 2H1, 4E6, 5Cl and PAb 8023 cross-reacted with potato acid phosphatase in ELISA, suggesting reactivity to conformationally similar epitopes. Thus, some of these reagents could be used in the development of standardised diagnostic immunoassays or as drug-targeting agents for conditions in which the pathological process involves bone resorption, the MAbs G211D, 2H1, 4E6, 5Cl and PAb 8023 being useful in ELISA but not immunocytochemical detection of TRAP.
Assuntos
Fosfatase Ácida/análise , Especificidade de Anticorpos , Ensaio de Imunoadsorção Enzimática/métodos , Imuno-Histoquímica/métodos , Isoenzimas/análise , Animais , Anticorpos Monoclonais , Reações Cruzadas , Cobaias , Humanos , Osteoclastos/enzimologia , Sensibilidade e Especificidade , Fosfatase Ácida Resistente a Tartarato , Trofoblastos/enzimologia , Células U937RESUMO
The identification of hepatitis A and hepatitis B led to the recognition that a third virus was capable of causing blood-borne hepatitis. The pathogen responsible for this nonA, nonB hepatitis was identified in the late 1980s and subsequently named hepatitis C. Since the discovery of hepatitis C there has been a pandemic of research publications describing the natural history of the infection and it is now known that this virus can cause serious liver damage in a proportion of infected patients. It is now clear that the effects of infection with hepatitis C and alcohol misuse are additive and that there is an increased risk of hepatic complications in infected patients who abuse alcohol.
Assuntos
Hepacivirus , Hepatite C Crônica , Transtornos Relacionados ao Uso de Álcool , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , HumanosAssuntos
Ascite/diagnóstico , Endometriose/diagnóstico , Cistos Ovarianos/diagnóstico , Derrame Pleural/diagnóstico , Fraturas das Costelas/diagnóstico , Adulto , Doenças Ósseas Metabólicas/diagnóstico , Cicatriz/diagnóstico , Feminino , Fraturas Espontâneas/diagnóstico , Humanos , Doenças Peritoneais/diagnóstico , Aderências Teciduais/diagnósticoRESUMO
Glycoprotein H/glycoprotein L (gH/gL) complexes of herpesviruses are required for fusion of infecting virions with host cell membranes. In human cytomegalovirus (HCMV), neutralizing monoclonal antibodies (MAb) specific for gH inhibit the transfer of a fluorescent probe to the host cell from labelled virus particles. In similar fashion, in the present study, neutralizing gH-specific MAb inhibited HCMV-induced fusion-from-without in monolayers of both human embryonic fibroblasts and continuous astrocytoma cells (U373). No fusion was detected in cells co-infected with defective recombinant adenovirus vectors that elicited high-level expression of gH and gL, indicating that surface-expressed gH was not intrinsically fusogenic. However, when such cells were superinfected with HCMV that gave fusion-from-without, the resulting cell-to-cell fusion was considerably enhanced. Thus, under our experimental conditions, gH/gL on the cell surface functioned to increase membrane fusion once this was initiated by other components in the virus envelope.
Assuntos
Citomegalovirus/patogenicidade , Fusão de Membrana/fisiologia , Proteínas do Envelope Viral/fisiologia , Adenoviridae/genética , Anticorpos Monoclonais/farmacologia , Sequência de Bases , Células Cultivadas , Citomegalovirus/genética , Citomegalovirus/fisiologia , Primers do DNA/genética , Dactinomicina/farmacologia , Vírus Defeituosos/genética , Humanos , Fusão de Membrana/efeitos dos fármacos , Reação em Cadeia da Polimerase , Recombinação Genética , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologiaRESUMO
The hypervariable region (HVR) of the E2/NS1 region of hepatitis C virus (HCV) varies greatly between viral isolates with high rates of genomic change reported during the course of chronic infection. The HVR is thought to encode a structurally unconstrained envelope protein containing several linear B cell epitopes recognized by neutralizing antibody. It has been postulated that amino acid changes in the HVR could result from humoral immune pressure leading to the selection of escape mutants. The aim of this study was to compare the rates of nucleotide and amino acid variation in the HVR of control patients to patients with common variable immunodeficiency (CVID) where the effect of the humoral immune system is reduced. Five controls and four patients with CVID were studied. Serum samples were taken over periods of between 1 and 6 years. HCV was detected by polymerase chain reaction (PCR) with primers derived from conserved flanking regions of the HVR. PCR products were cloned into a plasmid vector and recombinant clones identified by restriction enzyme digestion. Purified DNA from at least three individual clones from each time point was sequenced by the dideoxynucleotide chain-termination method. Consensus sequences were extracted from the three clones, and the DNA and deduced protein sequences were compared. Control patients had a mean rate of nucleotide change of 6.954 nucleotide substitutions per year, compared with patients with CVID with a rate of 0.415 nucleotide substitutions per year (P < .02). The corresponding rates for amino acid variation were 3.868 amino acid substitutions per year for the control patients compared with 0.185 amino acid substitutions per year for the patients with CVID. These findings suggest that in the absence of humoral immune selective pressure, the frequency of occurrence of genetic variation in the major viral species is reduced. The mutations occur, but in the absence of immune selection remain as minor species. The evolution of viral mutants capable of evading the host's immune system may contribute to the ability of HCV to establish chronic infection.
Assuntos
Agamaglobulinemia/genética , Variação Genética , Hepacivirus/genética , Adulto , Agamaglobulinemia/sangue , Agamaglobulinemia/virologia , Sequência de Aminoácidos , Sequência de Bases , Sequência Conservada , Feminino , Variação Genética/fisiologia , Hepacivirus/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Valores de Referência , Viremia/complicaçõesRESUMO
BACKGROUND: There is great disparity in the literature as to the presence and relevance of enterovirus in heart tissue from patients with dilated cardiomyopathy (DCM). Published estimates of enteroviral positive tissue in DCM range from 0 to 50%. Very little sequence information is so far available on those samples which are positive. HYPOTHESIS: Re-examination of fresh biopsy material from patients previously tested, plus 13 new cases of DCM, and sequencing the products would yield information on the validity of the technique and on the type of virus being detected. METHODS: RNA from biopsy or explant tissue was tested for the presence of enterovirus using reverse transcriptase polymerase chain reaction (PCR). The nucleotide sequences of all positive PCR products were determined by direct sequencing. RESULTS: Positive PCR signals were found in 10% of samples from patients with DCM and in 16% of control tissues. Two DCM and 12 control samples gave the same nucleotide sequence, which was different from the CB3 used as a positive control. The other 4 DCM samples all produced multiple bands on sequencing. CONCLUSION: The results do not support a major role for enterovirus in DCM. There is need for some caution, however, as a review of the literature shows that studies using single biopsies, such as this one, produce consistently lower estimates for enterovirus than do those wherein multiple biopsies are examined.
Assuntos
Cardiomiopatia Dilatada/virologia , Infecções por Enterovirus/complicações , Enterovirus/genética , Reação em Cadeia da Polimerase , RNA Viral/análise , Adolescente , Adulto , Idoso , Anticorpos Antivirais/análise , Sequência de Bases , Biópsia , Cardiomiopatia Dilatada/patologia , Enterovirus/imunologia , Infecções por Enterovirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Sondas RNA/química , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The histological description of chronic hepatitis is undergoing considerable change at present. It has become important to define chronic hepatitis aetiologically and then define levels of necro-inflammatory change (grade) and fibrosis (stage). The aim of this study was to compare the ability of different histological scoring systems to detect differences in the pathological changes associated with infection with the different HCV genotypes that are known to have different natural histories. The histological appearances of liver biopsies from 29 HCV infected patients were compared by the Knodell histological activity index (HAI), modified histological activity index and the Scheuer histological scoring system. HCV genotyping was performed for each patient by sequence analysis of the 5' non-coding region. The histological appearances from HCV 1 infected patients showed a tendency towards more active necro-inflammatory changes when compared with those from HCV 2 or 3 infected patients. The levels of fibrosis were similar for all genotypes. The modified HAI and Scheuer scoring systems detected differences, not revealed by the Knodell system, in the types of inflammatory pathology produced by the different genotypes of HCV. In particular these scoring systems noted significant differences in the component scores of inflammation, in addition to the total inflammatory scores. In conclusion, the recently introduced scoring systems were able to detect differences in liver pathology produced by infection of similar duration with different viral genotypes. As genotype is considered an important determinant of disease progression and response to anti-viral therapy, it is likely that those scoring systems correlating with genotype will yield more useful histological information than those that do not.
Assuntos
Hepacivirus/genética , Hepatite C/patologia , Fígado/patologia , Adulto , Idoso , Doença Crônica , Feminino , Genótipo , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Viral/genética , Análise de SequênciaRESUMO
We have observed transient elevations of serum alanine transaminase (ALT) levels in patients with aplastic anaemia who have been treated with antithymocyte globulin (ATG). Out of 18 patient episodes analysed retrospectively over a 12 month period, 15 experienced increases in ALT levels with values ranging from 1.2 to 18.5 times the upper limit of normal. In 11 of 15 episodes this was transient with ALT values returning to normal by 30 days, but in two patients this persisted for 6 months, and in a further two, until death at 34 and 145 days from unrelated causes. There was no evidence of acute viral infection or reactivation and no other drug toxicity could be implicated. We conclude that this may represent either a non-specific binding effect of ATG to hepatocytes or infection with an unidentified agent.
Assuntos
Anemia Aplástica/tratamento farmacológico , Soro Antilinfocitário/efeitos adversos , Imunossupressores/efeitos adversos , Fígado/fisiopatologia , Adolescente , Adulto , Anemia Aplástica/sangue , Soro Antilinfocitário/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Fígado/enzimologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Transaminases/sangueAssuntos
Infecções por Coxsackievirus/virologia , Cardiopatias/virologia , Adulto , Cardiomiopatias/virologia , Criança , Pré-Escolar , Infecções por Coxsackievirus/diagnóstico , Enterovirus Humano B/genética , Enterovirus Humano B/imunologia , Enterovirus Humano B/patogenicidade , Humanos , Miocardite/virologia , Pericardite/virologiaRESUMO
Retrospective and prospective analyses of heart transplant recipients showed no significant association between acute rejection and the detection of cytomegalovirus (CMV) infection by culture or the polymerase chain reaction (PCR) for viral DNA, neither on grounds of the incidence of both conditions nor in relation to which was diagnosed first in the patient. Semiquantitative PCR of serial blood and endomyocardial biopsy specimens from individual patients revealed different patterns in the development of the viral DNA in the blood and the heart, also clear episodes of CMV infection in CMV antibody-negative recipients of hearts from CMV antibody-negative donors, none of whom went on to develop a CMV-specific antibody response. None of these findings was associated with the development of rejection in the patient. On the other hand, in those patients who did experience rejection, peak levels of CMV DNA in the blood and the heart were usually not reached until 6 weeks or more after transplantation, whereas in those in whom rejection was not detected at all during the period of observation, peak levels of CMV DNA were detected earlier, mainly within the first 6 weeks after transplantation. In several cases, the delayed increase in CMV DNA in those with rejection, albeit not the delay itself, was linked to treatment with steroids. These findings support the view that CMV infection and rejection are independent events, but that the timing of the infection, and whether or not rejection is detected, are indicative of the general status of the immune response in individual patients.