PubMed Health⌕ Search

Biomedical subjects

L Grillner

Publications and source records attributed to L Grillner.

At least 37 records · Page 2Linked to original sources

A prospective study of rapid methods of detecting cytomegalovirus in the blood of renal transplant recipients in relation to patient and graft survival.

Eighty-five renal transplant recipients were prospectively monitored for CMV infection up to 4 months post-transplantation by virus isolation from leukocytes, CMV antigen detection (pp65) in peripheral blood leukocytes (PBL), polymerase chain reaction (PCR) of alkaline treated plasma (P-PCR), PCR of extracted DNA from PBL (L-PCR) and serology. Additionally univariate and multivariate analyses of risk factors for patient and graft survival up to 4 yr post-transplantation were performed. The incidence of CMV infection was 78% and of CMV disease 33%. Antigen detection in PBL was positive before or at onset of symptoms in 23/24 (96%) evaluable patients with CMV disease. The corresponding figures for virus isolation were 22/24 (92%), P-PCR 21/24 (88%) and for L-PCR 18/24 (75%). The percentage of negative samples in patients without CMV disease was 89% for the antigen test, 92% for L-PCR and 83% for virus isolation and P-PCR. One rapid test (antigen test, P-PCR or L-PCR) was positive at a median of 16 d before the onset of symptoms. The antigen test was generally the first rapid test to become positive. CMV disease did not affect graft survival in the multivariate analysis but was associated with decreased patient survival.

Adolescent↗

Frequent patient-to-patient transmission of hepatitis C virus in a haematology ward.

Blood transfusion is a well-documented route of transmission of hepatitis C virus (HCV). However, a persisting high frequency of HCV infections was recorded in our haematology ward even after screening of blood donors had been introduced. We investigated the viral strains in 37 patients with haematological malignant diseases who had developed hepatitis C when treated in the ward during 1990-93. 17 of the patients acquired hepatitis C despite being transfused only with blood components screened by second-generation anti-HCV tests. The viral strains were characterised by PCR genotyping and nucleotide sequencing of the hypervariable region of the E2 gene. Five clusters of closely related or identical viruses were found involving 2, 3, 4, 6, and 15 patients, respectively. Blood components could be ruled out as the common source of infection because no donor had given blood to all patients sharing a specific strain, and even donors whose blood had been given to several patients were negative for HCV RNA. All patients in each cluster had been treated in the ward during overlapping periods. These findings suggest that despite strict hygienic control, HCV transmission occurred between patients treated in the same hospital setting, as has previously been reported in a smaller group of haemodialysis patients.

Adult↗

Nosocomial spread of hepatitis B virus (HBV) in a haemodialysis unit confirmed by HBV DNA sequencing.

An outbreak of hepatitis B virus (HBV) infection in a haemodialysis unit is described. Four patients in the unit contracted subclinical HBV infection within three months. DNA sequence analysis of the S gene of HBV isolates from chronic carriers and newly infected patients in the unit aided in tracing possible transmission pathways. Three newly infected patients had received partial or complete HBV vaccination previously. HBV was rapidly cleared from all three although the anti-HBs titre had not reached 10 IU L-1 in any of them at the time of infection.

Cross Infection↗

Chronic hepatitis C in alcoholic patients: prevalence, genotypes, and correlation to liver disease.

BACKGROUND: Only one-fifth of chronic alcoholic patients develop chronic liver disease in spite of continuous alcohol abuse. Hepatitis C has been proposed to be one of several suggested factors contributing to the development of liver disease. METHODS: In 201 consecutive chronic alcoholic patients admitted to the hospital for detoxification, antibodies to hepatitis C virus (HCV) were determined, using second-generation enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA) tests. Sera from patients with antibodies were tested with polymerase chain reaction (PCR) to detect HCV RNA and subsequently genotyped. RESULTS: Twenty-nine patients (14%) were positive in the ELISA and RIBA tests. HCV RNA was detected in 23 of the 29 (79%); 21 could be genotyped. Previous intravenous drug abuse was present in 18 of 29 (58%) in the positive group versus 3 of 172 (2%) in the negative group (p < 0.001), whereas the prevalence of previous blood transfusions did not differ between the groups. In one-third of the positive cases no obvious route of transmission was found. On the basis of clinical and biochemical variables and, if available, histology, altogether 6 of 29 (21%) HCV-positive patients were classified as having severe liver disease as compared with 12 of 172 (7%) HCV-negative patients (p < 0.05). HCV-positive patients with liver disease were younger than HCV-negative patients with liver disease (p < 0.05). CONCLUSIONS: Hepatitis C virus infection is common among chronic alcoholic patients in Stockholm, especially among patients with a history of intravenous drug abuse. To confirm ongoing infection, detection of HCV RNA is necessary. This infection seems to be a factor contributing to the development of liver disease in alcoholic patients.

Adult↗

Diagnostic markers and risk factors of cytomegalovirus infection and disease in renal allograft recipients.

In a prospective study, the incidences of CMV infection and disease were 56 and 23%, respectively, during the first 6 months following kidney transplantation. Viremia was found in all patients with CMV disease and arthralgia was present in 71% prior to the development of CMV disease. The positive predictive value for CMV disease reached up to 90% for viremia and arthralgia in combination. Viruria was poorly correlated to viremia and hence CMV disease. The majority of patients (93%) who developed CMV disease had a seropositive donor, and viremia was significantly more common in patients who received CMV-seropositive kidneys. CMV disease was more common in CMV-seronegative recipients than in seropositive recipients. The 1-year graft survival rate was 75% in the entire study group. In patients with CMV viremia and disease, the rates were 78 and 73%, respectively. Antiviral treatment was initiated within 3 weeks of viremia detection in the 6 patients with CMV disease who survived. We found that the combination of arthralgia and viremia was a useful predictor of CMV disease and that recipients of CMV-seropositive allografts were at a greater risk of developing CMV disease. To obtain an early diagnosis and commence an early treatment of CMV disease, patients prone to develop CMV disease should be identified and clinical examination and viremia surveillance should be performed regularly.

Adolescent↗

Hepatitis C transmission in a hemodialysis unit: molecular evidence for spread of virus among patients not sharing equipment.

Three cases of simultaneous seroconversion to hepatitis C virus (HCV) in a hemodialysis unit initiated the investigation of the viral strains of 14 seropositive patients in the unit by nucleotide sequencing. The results showed that five patients had been infected with the same viral strain, and indicated that two other patients were sharing a second strain. Transmission was not related to blood transfusions and not associated with the dialysis machines, but occurred between patients treated on the same shift. The number of cases was higher than expected from the serological data. Thus, spread of virus may occur at high frequencies in environments where parenteral routes are made accessible, in spite of rigorous preventive measures. This may raise concern that non-transfusion associated spread of HCV may be present and unnoticed in several hospital settings.

Base Sequence↗

HTLV-I and -II in intravenous drug users from Sweden and Denmark.

693 IVDU (intravenous drug user) sera from Copenhagen, Malmö and Stockholm were tested, 247 retro- and 446 prospectively, for antibodies to human T-lymphotropic virus (HTLV), types I and II, by means of a commercial whole-virus EIA and/or an HTLV-I/-II peptide-based EIA. Positive EIA reactions were checked and typed by electrophoretic immunoblotting, a differential peptide-based EIA and nucleic acid amplification/hybridization with HTLV-I and -II specific primers and probes. 3 (0.7%) of the prospectively tested IVDUs from Malmö, none of 100 from Stockholm and none of 45 from Copenhagen were HTLV-seropositive. The 3 Malmö IVDU cases were a female immigrant from South America, her male native Swedish spouse (both HTLV-I), and a male immigrant Italian heroinist (HTLV-II). We conclude that HTLV was uncommon among intravenous drug users, a sentinel population, in Sweden and Denmark during 1986 and 1989. However, the occurrence of 3 HTLV-positive cases in Malmö 1993 indicates that the situation can change rapidly.

Adult↗

Microtiter assay for colorimetric detection of in vitro amplified Chlamydia trachomatis sequences.

An integrated diagnostic method for colorimetric detection of polymerase chain reaction (PCR) products in a microtitre format is described. The amplified material is labelled by using modified PCR primers introducing a biotin molecule and a lac operator handle. Positive samples are identified, after immobilization onto streptavidin-coated microtitre wells, using a reporter fusion protein consisting of the Escherichia coli lac repressor and beta-galactosidase. The analysis of the PCR products is thus, from a practical point of view, identical with the enzyme-linked immunosorbent assay (ELISA) using the enzymatic activity of beta-galactosidase. Here, we show that the assay can be used for rapid and simple detection of Chlamydia trachomatis in an automated format. The reported analysis of 90 urethral patient samples, using this microtitre assay, indicates that this technique is more sensitive and more specific than culture technique.

Base Sequence↗

Severe aplastic anemia associated with seronegative community-acquired hepatitis C virus infection.

Aplastic anemia (AA) is a rare complication of viral hepatitis affecting mainly children or young adults. Most reported cases have been associated with community-acquired non-A, non-B hepatitis, but hepatitis A and B have also been implicated in a few patients. We report on a 43-year-old woman with severe AA, in association with acute hepatitis C virus (HCV) infection, diagnosed by detection of HCV RNA by the polymerase chain reaction technique. Her AA was successfully treated with anti-thymocyte globulin and cyclosporin A. The hepatitis C progressed to chronic disease but, despite a follow-up time of 2 years, the patient still has no detectable anti-HCV antibodies, as evaluated with a second-generation anti-HCV assay.

Adult↗

Late seroconversion and high chronicity rate of hepatitis C virus infection in patients with hematologic disorders.

BACKGROUND: Patients with hematologic disorders requiring repeated blood and platelet transfusions are at high risk for development of post-transfusion non-A, non-B hepatitis. PATIENTS AND METHODS: Fifty-five patients with hematologic diseases and post-transfusion non-A, non-B hepatitis were studied. Sera were assayed for hepatitis C virus (HCV) antibodies with a second-generation enzyme-linked immunoassay. Sera from 40 patients were examined for the presence of HCV RNA with a nested PCR method. RESULTS: The clinical picture of acute non-A, non-B hepatitis did not differ from that described in other patient groups: however, progression to chronic hepatitis was very common (95%). Thirty-eight (95%) of 40 patients, whose sera were analysed both serologically and for the presence of HCV RNA had verified HCV infections. In some patients time to seroconversion was prolonged, up to more than 14 months. Seventeen patients with resistant or relapsed acute leukemia were treated with combination chemotherapy during the acute or chronic phase of hepatitis. Suppression of the inflammatory activity as reflected by a decrease of serum aminotransferase levels was recorded during the subsequent pancytopenic period. CONCLUSIONS: Hepatitis C has a high chronicity rate in patients with hematologic disorders which parallels the situation of hepatitis B in the immunocompromised host. Furthermore, like the situation in hepatitis B, the hosts' immune response to infection seems to be involved in the pathogenesis of liver injury. Time to seroconversion may be prolonged and detection of HCV RNA is therefore important for diagnosis.

Adolescent↗

Seroconversion to hepatitis C virus in dialysis patients: a retrospective and prospective study.

The prevalence and incidence of hepatitis C virus (HCV) infections were studied in 236 dialysis patients and related to clinical data at two hospitals in Stockholm, Sweden. Patients were followed during 12 months and tested by 1st- and 2nd-generation anti-HCV assays. Time of seroconversion to HCV could be determined by retrospective analysis of stored serum samples. A total of 36 (15%) patients were anti-HCV positive. Time of seroconversion could be determined for 23 patients and was in the majority of cases associated with blood transfusions, but late seroconversion (more than 6 months after transfusion) as well as lack of transfusion in some cases implied that HCV might be transmitted through dialysis equipment. Persistence of elevated alanine amino-transferase levels for more than 6 months occurred in 17% of anti-HCV-positive patients. In conclusion, routes of transmission in dialysis units have to be further evaluated since routes other than transfusion may occur and diagnosis may be delayed in this group of patients probably due to a poor immunological response.

Alanine Transaminase↗

A prospective study of first attacks of inflammatory bowel disease and non-relapsing colitis. Microbiologic findings.

In 105 patients with a first attack of colitis, thorough microbiologic investigations of rectal biopsy, faecal, and serum samples were performed with the aims of identifying the colitis-causing agents and shedding light on factors that may precipitate or aggravate the onset of inflammatory bowel disease. Sixty-one patients were found to have inflammatory bowel disease. In 13 (21%) of these patients microbial findings were positive. Eight of the 61 patients fell ill during or immediately after antibiotic treatment, and 10 while travelling abroad. Forty-one of the 105 patients had non-relapsing colitis. In 32 (78%) of these the microbial findings were positive. Six of these 41 patients fell ill during or immediately after antibiotic treatment, and 14 while travelling abroad. Alteration of the intestinal microflora on travelling, gastrointestinal infection, or treatment with antibiotics seems to precipitate or aggravate the symptoms in latent inflammatory bowel disease. In such patients the mode of onset is often changed from insidious to more acute, which may cause difficulty in differentiation from non-relapsing colitis.

Acute Disease↗

HIV-antibody testings among injecting drug users (IDUs) in the Stockholm area, 1984-91: information compiled from testing laboratories.

The available information about testings for HIV antibodies in injecting drug users (IDUs) carried out in Stockholm between 1984 and 1992 has been compiled. These testings were carried out mainly in special settings. The use of codes (the first 2 digits giving the age and the last 4 the 6 and checking figures in the individual's personal identity number) precluded exact identification of individuals; in most cases, however, complementary information made it possible to recognize patients at follow-up. The data indicated that 9,150 persons associated with current or previous drug addiction were tested. The first extensive testings were performed in 1985 and 1986. After this period, 4,500 persons were retested. 11% of the IDUs tested in 1984-85 were found to be HIV-antibody-positive. After 1988, 1% were estimated to seroconvert each year. While in the first phase the heroin users predominated among those infected, in later years the rates of newly diagnosed infections became similar for all types of IDUs. The age profiles of the IDUs tested were similar up to 1988, after which there was an indication that also younger persons had entered the scene. However, the infected IDUs discovered belonged mainly to the 'old' cohort born between 1950 and 1960.

Adult↗

Chlamydia pneumoniae in Swedish patients.

Chlamydia pneumoniae infections have earlier been described as mycoplasma-like illnesses in young people, and also appear to be associated with community-acquired pneumonia in adults. In this retrospective study, 12.2% (23/188) of patients with pneumonia who required hospitalization during the 3 years 1985-87 had serological evidence of recent C. pneumoniae infection. Many of these patients had symptoms similar to ornithosis. The most interesting finding was that half of the patients with a 4-fold IgG antibody titre rise to C. pneumoniae also had an increased alkaline phosphatase concentration.

Alkaline Phosphatase↗

The DNA-binding protein P52 of human cytomegalovirus reacts with monoclonal antibody CCH2 and associates with the nuclear membrane at late times after infection.

Monoclonal antibody CCH2 is commonly used for the detection of human cytomegalovirus (HCMV) infected cells in tissue sections as well as in cultured cells. The specificity of CCH2 was determined by screening a recombinant lambda-gt11 cDNA gene bank from HCMV-infected fibroblasts. By sequencing a reactive clone, the antigen was identified to be the non-structural DNA binding protein p52 of HCMV (UL44 reading frame). The viral insert from the lambda clone was recloned in bacterial expression vectors. For this, a new vector, pRos-RS, was constructed. The resulting clones were tested in immunoblot analyses. They were reactive with CCH2 as well as with reconvalescent sera positive for antibodies against HCMV, by this proving the specificity of CCH2. Using this monoclonal antibody in confocal microscopy, the subcellular localization of p52 in infected cells was analyzed. In these analyses, p52 was found to be nuclear and to be associated with the nuclear membrane at late times after infection.

Amino Acid Sequence↗

Seroconversion to hepatitis C virus antibodies in patients with acute posttransfusion non-A, non-B hepatitis in Sweden with a second generation test.

28 patients with posttransfusion non-A, non-B (NANB) hepatitis in Stockholm, Sweden, were studied for seroconversion to hepatitis C virus antibodies (anti-HCV) and time lag to seroconversion by first and second generation tests. 15/28 patients (54%) seroconverted to anti-HCV with a first generation anti-HCV ELISA using C100-3 from the nonstructural (NS) region 4 of the HCV genome and 23 (82%) with a second generation anti-HCV ELISA including also antigens from the core and NS3 regions of the HCV genome. The mean time from onset of hepatitis to seroconversion was 6.1 weeks (0-18 weeks) with the first generation test and 2.3 weeks (0-7 weeks) with the second generation test. Development of chronic hepatitis was noticed in 14/23 (61%) patients who seroconverted to anti-HCV with the second generation ELISA and in none of 5 patients with posttransfusion NANB hepatitis who did not seroconvert. The inclusion of antigens from the core and NS3 regions of the HCV genome has increased the sensitivity of the second generation anti-HCV ELISA as compared to the first generation ELISA and also shortened the time lag to seroconversion in patients with posttransfusion hepatitis C. Patients with posttransfusion NANB hepatitis seroconverting seem more prone to develop chronic disease than patients not seroconverting.

Enzyme-Linked Immunosorbent Assay↗

Early detection of cytomegalovirus in cell culture by a new monoclonal antibody, CCH2.

A CMV monoclonal antibody, CCH2, produced in this laboratory was evaluated for rapid detection of CMV. Two staining procedures, immunofluorescence and an immunoenzymatic technique using biotin-streptavidin peroxidase, were compared. The CCH2 monoclonal antibody was used to demonstrate early CMV antigen in cell culture 24 h after inoculation of 598 urine samples from kidney transplanted patients by indirect immunofluorescence in comparison with virus isolation. One hundred and sixty of the specimens were stained additionally by an immunoenzymatic technique and the results were compared. CMV was isolated from 170 out of 598 specimens within 6 weeks. Early CMV antigen was demonstrated in 114 of these specimens by immunofluorescence giving a sensitivity of 67% and a specificity of 95%. In the comparison with the immunoenzymatic staining procedure the results for all three tests agreed for 81% (130/160) of the specimens. After resolving discordant results into true positives and true negatives, the sensitivity was 87, 85 and 70%, respectively for virus isolation, immunoenzymatic staining and immunofluorescence and the specificity 100, 96 and 99%. The CCH2 monoclonal antibody proved to be useful for rapid detection of CMV in urine specimens and using immunoenzymatic staining with biotin-streptavidin a sensitivity comparable to that of virus isolation was found.

Antibodies, Monoclonal↗