E Holter

University of Oslo, Oslo, Oslo, Norway

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Publications (17)48.86 Total impact

  • Article: Cytomegalovirus DNA concentration in plasma predicts development of cytomegalovirus disease in kidney transplant recipients.
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    ABSTRACT: The clinical significance of cytomegalovirus (CMV) DNA detection in post-kidney transplantation infection surveillance was examined by comparing the performance of three assays for detection of CMV in blood: the test for CMV-pp65-antigen in leukocytes, which is routinely employed in our laboratory, the quantitative plasma CMV-DNA-polymerase chain reaction (PCR; Cobas Amplicor CMV Monitor test) and the qualitative plasma CMV-DNA-PCR (Amplicor CMV test). Thirteen kidney transplant recipients were monitored with serial samples taken over a period of 3 months following transplantation. The quantitative CMV-PCR was the test with highest sensitivity, 95.9%, vs. 88.9% and 76.9% for the CMV-pp65 antigen assay and qualitative CMV-PCR, respectively. The virus load in the first positive specimens, assessed as DNA-copies/mL, was significantly associated with CMV disease because five of the six patients who developed disease, but only one of the seven who did not develop disease, had more than 3000 CMV-DNA-copies/mL. The number of CMV-pp65 antigen-positive cells in the first positive specimens did not have predictive value for development of CMV disease. Assessment of CMV in plasma by the quantitative CMV-PCR is especially useful since it has a high sensitivity and the amount of CMV DNA in plasma is a good predictor of CMV disease.
    Clinical Microbiology and Infection 08/2002; 8(7):431-4. · 4.54 Impact Factor
  • Article: Detection of human cytomegalovirus (HCMV) pp67-mRNA and pp65 antigenemia in relation to development of clinical HCMV disease in renal transplant recipients.
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    ABSTRACT: To evaluate the performance of the recently introduced method based on detection of human cytomegalovirus (HCMV) pp67 mRNA in blood by the nucleic acid sequence-based amplification (NucliSens), in comparison to semiquantitative detection of pp65 HCMV antigen in white blood cells, in relation to development of clinical HCMV disease. Thirty patients, recipients of renal transplants, were monitored prospectively for the presence of pp67 mRNA, the presence and level of pp65 antigenemia, IgG and IgM antibodies, and the development of clinical HCMV disease. A total of 148 samples were examined during the observation period. Twenty-five samples were positive for pp67-mRNA and 45 samples contained at least one pp65 positive cell, with 68% agreement between the two assays. Both assays predicted correctly the development of clinical disease in five patients, giving a sensitivity of 100%. However, the specificity of the pp67-mRNA test was 72%, and of the pp65 antigenemia test from 20 to 64%, depending on the level of antigenemia chosen for cut-off. pp67-RNA appeared somewhat earlier than pp65 antigenemia, and responded earlier to treatment. Sero-conversion and appearance of IgM antibodies were of very little clinical value. Both the pp67-mRNA and the pp65 antigenemia assay predicted correctly the development of clinical HCMV disease in renal transplant recipients. However, the specificity of both tests with respect to development of HCMV disease, especially the pp65 antigen test was moderate. Significantly positive tests not necessarily prove the development of clinical disease. Testing for pp67-mRNA may improve the diagnosis and management of HCMV disease in renal transplant patients.
    Clinical Microbiology and Infection 06/2001; 7(5):254-60. · 4.54 Impact Factor
  • Article: A prospective study of the natural course of cytomegalovirus infection and disease in renal allograft recipients.
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    ABSTRACT: Cytomegalovirus (CMV) infection is the single most frequent infectious complication in renal transplant recipients. Because no CMV-prophylaxis is given and ganciclovir is used only as deferred therapy for CMV disease at our center, we have been able to study the natural course of CMV infections. The aim was to assess risk factors for CMV infection and disease and thus identify subgroups of patients likely to benefit from CMV prophylaxis or preemptive therapy. Between October 1994 and July 1997, 477 consecutive renal transplant recipients (397 first transplants and 80 retransplants) were included in the study. The patients were followed prospectively for 3 months with serial measurements of CMV pp65 antigen for monitoring activity of CMV infections. The incidence of CMV infections in first transplants was 68% in D+R- and D+/-R+ serostatus groups, whereas the incidence of CMV disease was higher in D+R- (56%) than in D+/-R+ (20%, P<0.001). No difference in severity of CMV disease in D+R- and D+/-R+ was seen except for an increased incidence of hepatitis in primary infections. One of 14 deaths could be associated with CMV disease in a seropositive recipient. Cox regression analysis showed that rejection (RR 2.5, P<0.01) and serostatus group D+R- (RR 3.9, P<0.001) were significant risk factors for development of CMV disease. The maximum CMV pp65 antigen count had significant correlation to disease only in CMV seropositive recipients, P<0.001. Conclusion. Renal transplant recipients can safely be given deferred ganciclovir therapy for CMV disease if they are intensively monitored for CMV infection. Patients with primary CMV infection (D+R-), CMV infected patients undergoing anti-rejection therapy and R+ patients with high CMV pp65 counts seem to have a particular potential for benefit from preemptive anti-CMV-therapy.
    Transplantation 10/2000; 70(8):1166-74. · 4.00 Impact Factor
  • Article: Discrepancy between results of a commercial enzyme immunoassay kit and immunofluorescence staining for detection of respiratory syncytial virus antigen.
    European Journal of Clinical Microbiology 09/1998; 17(8):595-6. · 2.86 Impact Factor
  • Article: Diagnosis of cytomegalovirus infection in kidney transplant recipients by a quantitative RNA-DNA hybrid capture assay for cytomegalovirus DNA in leukocytes.
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    ABSTRACT: The clinical value of a new RNA-DNA hybridization assay for quantification of cytomegalovirus (CMV) DNA in leukocytes [Hybrid Capture CMV DNA Assay (HCA); Murex Biotech, UK] was evaluated. The HCA was compared with an assay for CMV pp65 antigen in leukocytes and an in-house CMV polymerase chain reaction PCR (CMV-PCR) on parallel blood samples. The HCA and the CMV-PCR were less sensitive than the CMV pp65 assay, but the positive predictive value of all three methods for CMV disease was 50% or less. However, when quantitation of viral load by HCA and CMV pp65 assay was taken into consideration, both assays were superior to CMV-PCR in predicting CMV disease.
    European Journal of Clinical Microbiology 03/1998; 17(2):124-7. · 2.86 Impact Factor
  • Article: Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis.
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    ABSTRACT: Overlapping features between primary sclerosing cholangitis (PSC and autoimmune hepatitis (AIH) have previously been noted. To assess systematically similarities between these disorders, we have evaluated 114 PSC patients (36 women; 78 men), all confirmed by endoscopic retrograde cholangiography (ERC), according to a scoring system proposed by The International Autoimmune Hepatitis Group for the diagnosis of AIH. The scoring system attributes positive or negative scores to the parameters sex, ratio of elevation of serum levels of alkaline phosphatase (ALP) vs. aminotransferase, serum levels of immunoglobulins and autoantibodies, viral markers, history of drug and alcohol intake, genetic factors, liver histology, and response to therapy. Two of the PSC patients (2%) obtained scores above 15 before treatment, satisfying the diagnostic criterion of "definite" AIH. Thirty-eight patients (33%) scored between 10 and 15 points and could be classified as "probable" AIH. The serum level of immunoglobulin G (IgG) was elevated in 68 patients (61% of 111 cases tested), and positive titers of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) were detected in 24 patients (22% of 111 cases tested). Thirty-five of the PSC patients (33% of 105 evaluable biopsy specimens) obtained positive scores for histological features similar to those of AIH, but the total score for histology was in the negative range in 72 patients (69%) because of the presence of biliary changes. The frequent finding of high scores in PSC patients underlines the similarities PSC may have with AIH. A modification of the scoring system, in particular by increasing the negative score for histological biliary changes, would improve its potential to discriminate between AIH and PSC.
    Hepatology 07/1996; 23(6):1369-76. · 11.66 Impact Factor
  • Article: Hepatobiliary disease in ulcerative colitis. An analysis of 18 patients with hepatobiliary lesions classified as small-duct primary sclerosing cholangitis.
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    ABSTRACT: The aim of the present study was to describe the characteristics of patients with ulcerative colitis (UC) and hepatobiliary disease that does not satisfy the diagnostic cholangiographic criteria of primary sclerosing cholangitis (PSC) and to compare this group with PSC patients. Among 199 patients with UC admitted to our department during 1986-91, 64 patients had major hepatobiliary disease considered to be associated with the colitis. Biochemical tests, colonoscopy, endoscopic retrograde cholangiography (ERC), and liver biopsy were performed in these 64 patients and in 5 patients from our outpatient clinic. PSC was diagnosed in 51 patients (group I; 80%). The other 13 patients (20%) and the additional 5 patients (n = 18; group II) all had normal extrahepatic bile ducts. Five patients in group II also had normal intrahepatic ducts, whereas 13 patients had intrahepatic abnormalities. The male to female ratio in group II was 2.0:1. All of them had extensive colitis. The clinical symptoms and the biochemical and histologic findings were quite similar in groups I and II. The patients in group II of this study constitute a major group with hepatobiliary lesions associated with UC, amounting to one-fourth the number of PSC patients. They have several similarities with classical PSC of the large bile ducts, and we suggest that they be classified as having small-duct PSC.
    Scandinavian Journal of Gastroenterology 09/1994; 29(8):744-52. · 2.02 Impact Factor
  • Article: Rapid detection of cytomegalovirus infection in immunocompromised patients.
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    ABSTRACT: Several routinely employed diagnostic methods were analysed for their usefulness in aiding an early and rapid diagnosis of human cytomegalo-virus infection in immunocompromised patients. Clinical samples obtained during an 18-month period were examined by conventional culture, the shell vial method, detection of pp65 antigen and the polymerase chain reaction. Detection of pp65 antigen in peripheral leukocytes was the most useful method for rapid detection of infection at an early stage. Results of other rapid detection methods, the shell vial method and the polymerase chain reaction, gave useful support, while results obtained by conventional culture were not available until after the initiation of therapy. Only a small proportion of serological tests provided useful information for determining whether to treat the patient.
    European Journal of Clinical Microbiology 09/1994; 13(8):668-70. · 2.86 Impact Factor
  • Article: [The TORCH study. A reevaluation].
    L W Holtmon, T W Hansen, E Holter
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    ABSTRACT: The TORCH panel is used to screen for congenital infection. The purpose of this study was to evaluate the use of TORCH by pediatricians and pediatric trainees in a university pediatric department. The patient charts corresponding to the 109 samples submitted to the Institute of Bacteriology from 1987-91 were reexamined for evidence suggestive of congenital infection. Generally, the charts contained little information that might explain the reason for ordering a full TORCH panel. None of the submitted samples yielded conclusive evidence of congenital infection. TORCH studies appeared to have been requested on very liberal indications. We conclude that the TORCH panel as used at present creates a lot of work for microbiologists, but yields little information. A more targeted approach to testing for congenital infection seems called for.
    Tidsskrift for Den norske legeforening 02/1994; 114(3):311-2.
  • Article: Daily home spirometry facilitates early detection of rejection in single lung transplant recipients with emphysema.
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    ABSTRACT: Eight single lung transplant recipients with emphysema, aged 40-58 yrs, have been followed up for 90 patient months. Starting 2-4 weeks postoperatively, they recorded their forced vital capacity (FVC), and forced expiratory volume in one second (FEV1), at a fixed time every morning using a Micro Spirometer. They were instructed to contact the hospital if the FVC or FEV1 displayed a persistent (two days or more) decrease of 10%, compared with the average values during the last seven days. Transbronchial biopsies (TBB) were performed regularly in the follow-up, and whenever the patients had respiratory symptoms, or the FVC or FEV1 displayed a persistent decline of more than 10%. We performed 59 TBBs, and 23 biopsy specimens showed rejection. The FVC and FEV1 values on the TBB day were compared with the mean values of the 7 previous days. FVC and FEV1, associated with negative TBBs (16 events), showed no significant changes. However, FVC and FEV1 decreased significantly (p < 0.001, paired t-test) during rejections (mean percentage change 14 and 21% respectively, range +8% to -53%). In 16 of the 23 rejections, the FEV1 decreased by > 10%. We recommend the use of daily home spirometry when monitoring single lung recipients with emphysema, and suggest that a persistent 10% decrease in FEV1 or FVC for at least two days is an indication for hospital admission and possible TBB.
    European Respiratory Journal 05/1993; 6(5):705-8. · 5.89 Impact Factor
  • Article: [Evaluation of virological/serological parameters for hepatitis B].
    E Holter
    Tidsskrift for Den norske legeforening 07/1992; 112(15):1965-6.
  • Article: Cytomegalovirus (CMV) pneumonitis in AIDS patients: the result of intensive CMV replication?
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    ABSTRACT: We report a case of fatal pulmonary disease in a patient infected with human immunodeficiency virus (HIV), where cytomegalovirus (CMV) was the only causative agent identified in the lungs at autopsy. The most prominent histopathological features were numerous interalveolar cells containing CMV inclusion bodies combined with scanty signs of inflammation. We propose that the lung damage caused by CMV in acquired immune deficiency syndrome (AIDS) patients is a direct consequence of cytopathogenic effects of the virus related to the extent of active virus replication.
    European Respiratory Journal 04/1992; 5(3):362-4. · 5.89 Impact Factor
  • Article: [Diagnosis of cytomegalovirus infections in hospitalized patients].
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    ABSTRACT: Rapid detection of cytomegalovirus (CMV) infections, especially in immunocompromised patients, is important and sometimes lifesaving. We describe one year's experience of using a combination of several methods: detection of "immediate early" CMV antigen in blood, detection of "early" virus antigen after brief incubation in cell culture, detection of viral DNA by polymerase chain reaction, regular culture in human embryo fibroblasts, and serological detection of IgM and IgG antibodies. A quick and early diagnosis was achieved by all three rapid methods. However, none of the methods is sufficiently sensitive or specific to allow it to be used alone. A combination of several methods is recommended in order to achieve maximum efficiency and safety.
    Tidsskrift for Den norske legeforening 12/1991; 111(28):3401-4.
  • Article: [Cytomegalovirus disease in the upper gastrointestinal tract. Endoscopic findings].
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    ABSTRACT: Cytomegalovirus disease is seen mainly in immunocompromised patients. While gastrointestinal symptoms are difficult to interpret, the typical finding at endoscopy of the upper alimentary tract is ulcers. Diagnosis of cytomegalovirus disease is based on typical histological findings in biopsy specimens. Antiviral treatment should be started when cytomegalovirus disease is detected in transplant patients. If it is decided to treat patients suffering from AIDS, lifelong maintenance treatment is required. Early diagnosis by means of endoscopy and biopsies is very important, and will decide the outcome of instituted treatment.
    Tidsskrift for Den norske legeforening 12/1991; 111(28):3391-3.
  • Article: [Cytomegalovirus disease in the gastrointestinal tract].
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    ABSTRACT: Cytomegalovirus infections in immunocompromised patients may cause serious illness, particularly in patients with HIV-disease and in transplant recipients. There is an increasing number of reports of cytomegalovirus infections involving the alimentary tract, especially colitis. Diagnosis of cytomegalovirus disease is at present based on specific histological findings. Antibody findings can be difficult to interpret. The slow growth of cytomegalovirus in cultures makes this method less useful in the acute setting of diagnosis. It is important to recognize cytomegalovirus colitis as a differential diagnosis to idiopathic inflammatory bowel disease. In fulminant disease, colectomy should be considered in addition to antiviral treatment.
    Tidsskrift for Den norske legeforening 12/1991; 111(28):3388-91.
  • Article: [Symptomatic cytomegalovirus infection in patients with acquired immunodeficiency syndrome].
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    ABSTRACT: During a seven-year period, symptomatic cytomegalovirus (CMV)-infection was diagnosed in 21.5% (n = 10) of all AIDS patients at the National Hospital of Norway (retinitis n = 8, colitis n = 3, pneumonitis n = 2, gastritis n = 1). Symptomatic cytomegalovirus-infection was associated with a poor long-term prognosis (median survival 174 days, range 10-415). Median CD4+ lymphocyte counts at onset of symptomatic cytomegalovirus-infection was 24 x 10(6)/l (range 6-68). Regular ophthalmological examination of HIV-infected patients with severe immunodeficiency, and endoscopy with multiple mucosal biopsies in patients with suspected cytomegalovirus-infection of the gastrointestinal tract, were of major importance in diagnosing symptomatic cytomegalovirus-infection. Six patients received an induction course of ganciclovir, and foscarnet was administered in two patients due to leukopenia. Problems of toxicity to the available anti-CMV agents make the development of additional therapeutic approaches desirable.
    Tidsskrift for Den norske legeforening 12/1991; 111(28):3379-84.
  • Article: Fatal cytomegalovirus (CMV) colitis in a patient receiving low dose prednisolone therapy.
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    ABSTRACT: Cytomegalovirus (CMV) colitis is uncommon in patients who are not gravely immunodepressed. We report a case of fatal CMV colitis in a 54-year-old woman on low dose steroid therapy. She was admitted to hospital after sudden onset of abdominal pain and hemorrhagic watery diarrhea. After 25 days in the hospital, treatment with high dosage of methylprednisolone was started for presumed ulcerative colitis. Her condition worsened and she died 52 days after admission. It is important to recognize CMV colitis as differential diagnosis to inflammatory bowel disease, particularly when the colitis is refractory to immunosuppressive treatment.
    Scandinavian Journal of Infectious Diseases 02/1991; 23(4):495-9. · 1.72 Impact Factor