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Biomedical subjects

B F Vestergaard

Publications and source records attributed to B F Vestergaard.

At least 55 records · Page 3Linked to original sources

Zidovudine treatment of AIDS and ARC in Denmark 1987.

In 1987, a total of 138 Danish patients (94 AIDS and 44 ARC) received treatment with zidovudine, a total observation period of 572 treatment months. 15 AIDS and 1 ARC patient died after a median of 70 days (range 2-295). In the ARC group 4 patients developed AIDS (3 Pneumocystis carinii pneumonia, 1 Kaposi's sarcoma). Among the AIDS patients 38 new opportunistic infections were reported. 24 of these opportunistic infections occurred within 6 weeks after treatment initiation. 79 patients were observed for more than 3 months, 25 of these had their daily dose zidovudine reduced, usually from 1,200 mg to 600 mg, 9 others were temporarily off drug. HIV antigen was analyzed in serum samples from 93 patients. Of these, 28 (52%) of 54 initially HIV antigen-positive became antigen-negative, 7 (18%) of 39 initially HIV antigen-negative became antigen-positive within the first 8 weeks of zidovudine treatment. In 57 patients the total count of CD4+ cells were evaluated. A significant increase in the number of CD4+ cells was observed during treatment. In nearly all patients an increase in MCV and a decrease in neutrophil count was observed. 44 of the patients received a total of 307 blood transfusions on 94 occasions and 19 (14%) patients required multiple transfusions. The mortality among the AIDS patients was significantly lower compared to historical controls. In our experience zidovudine treatment is reasonably well tolerated and the side effects are manageable.

AIDS-Related Complex↗

Oral acyclovir suppressive therapy in severe recurrent genital herpes. A double-blind, placebo-controlled cross-over study.

A randomised, double-blind, placebo-controlled cross-over study was conducted in 24 patients, nine females and 15 males, with a history of more than eight recurrences of genital herpes in the past year. The patients received a first treatment course with 400 mg acyclovir or matching placebo by mouth, twice daily, for 12 weeks. After cross-over patients received alternative medication for another 12 weeks. The patients were followed without treatment for a further three-month period. During acyclovir therapy, recurrences were completely prevented in 17 patients (71%) and the remaining seven patients had nine recurrences as compared to 18 recurrences while receiving placebo. The placebo treatment did not reduce the recurrence rate. No adverse effects were attributable to the acyclovir treatment period. All virus isolates tested after treatment remained sensitive to acyclovir. Acyclovir prophylaxis of recurrent genital herpes is effective and safe. A continuous suppressive therapy with acyclovir offers a basis for a normal sexual life to those patients severely incapacitated by their disease, but once medication is stopped, patients shed virus as before suppression.

Acyclovir↗

Human papillomavirus, herpes simplex virus and cervical cancer incidence in Greenland and Denmark. A population-based cross-sectional study.

In Greenland, the incidence of cervical cancer is 5.7 times higher than in Denmark among women aged 20-39. From Nuuk (Greenland) and Nykøbing Falster (Denmark) a sample of 800 women aged 20-39 years was drawn at random. A total of 586 and 661 women were investigated in Greenland and Denmark respectively. All women had a gynecological examination including a PAP-smear and cervical scrape for HPV-analysis (filter in situ hybridization). A blood sample was taken for analysis of HSV type-specific antibodies (ELISA). The percentage of normal smears was identical in the 2 areas (95%). The total HPV 16/18 infection rate was 13% in Denmark and 8.8% in Greenland, and the age-adjusted prevalence rate in Greenland was only 67% of that in Denmark (95% CI: 0.05-0.89). The proportion of HPV 6/11 positivity was the same in Greenland and in Denmark (6.7% vs. 7.5%). A significantly higher proportion of the Greenlandic women had HSV-2 antibodies (68.2%) in comparison with Danish women (30.9%) (p less than 0.01). The prevalence of HSV-1 was also higher in Greenland, especially in women aged 20 to 24. Our finding of a higher HPV infection rate in Denmark than in Greenland, opposed to cervical cancer rates, does not support a role for these viruses as determinants of cervical cancer incidence. In contrast, the rate of HSV-2 infection co-varies with the observed incidence of cervical cancer. This is in line with the notion that differences in cervical cancer incidence between Denmark and Greenland are determined by aspects of sexual behavior.

Adult↗

Temporal relation of antigenaemia and loss of antibodies to core antigens to development of clinical disease in HIV infection.

A total of 276 sequential serum samples from 34 men with antibodies to the human immunodeficiency virus (HIV) followed up for two to seven years were analysed for HIV antigen and antibodies to the viral core and envelope proteins. Results were correlated with clinical outcome and CD4 T lymphocyte count. Both antigenaemia and the disappearance of antibodies to the core protein were associated with development of the acquired immune deficiency syndrome (AIDS) or AIDS related complex and depletion of CD4 cells. Thus AIDS or AIDS related complex developed in eight out of 16 patients with antigenaemia compared with one out of 18 patients without antigenaemia. Low counts of CD4 cells (less than 0.5 X 10(9)/l) were found in 14 of the 16 patients with antigenaemia and five of the 18 without antigenaemia. Nine patients seroconverted to HIV during the study; two of these developed antigenaemia 14 and 16 months after the estimated time of seroconversion. These results show that the late stages of HIV infection are characterised by increased production of antigen and a decrease in antibodies directed against the core protein. Antigenaemia indicates a poor prognosis; and as the antigen test is simple to do and interpret, it may therefore be useful for selecting patients for antiviral treatment.

AIDS-Related Complex↗

An enzyme labelled nuclear antigen immunoassay for detection of cytomegalovirus IgM antibodies in human serum: specific and non-specific reactions.

A mu-capture enzyme linked immunosorbent assay was developed for detection of IgM antibody to cytomegalovirus (CMV). Virus-specific IgM was detected using horseradish peroxidase labelled nuclear CMV antigen (CMV-ELA). False-positive reactions caused by Paul-Bunnell-Davidsohn (PBD) positive sera and antinuclear antibody (ANA) positive sera were identified in a combination assay employing enzyme labelled nuclear control antigen (CO-ELA) in parallel to the CMV-ELA. Four of five PBD positive and 30 of 31 ANA positive sera reactive with the CMV-ELA were identified as false positive reactions in the combined ELA-assay. The reactivity in PBD-positive sera could not be explained by antigenic cross reactivity between CMV and Epstein-Barr virus, and the results further suggested that different cell specified components of the CMV-ELA were responsible for the reactivity of PBD-positive as compared to ANA-positive sera. One of 314 healthy blood donors, 12 of 12 patients with primary CMV infection, and 11 of 15 patients with secondary CMV infection had detectable CMV IgM antibodies. Comparison of different CMV-ELAs revealed that pronounced differences in specificity as well as sensitivity may exist.

Antibodies, Antinuclear↗

A biotin-avidin-amplified inhibition enzyme immunoassay for detection of CMV antibodies in human serum.

In this inhibition immunoassay undiluted serum reacts in solution with crude cellular CMV antigen in wells of microtestplates coated with hyperimmune CMV-reactive monkey IgG. CMV antibodies in the serum under test block (completely or partial) the fixation of antigen to the capture layer. Unblocked antigenic activity is in subsequent steps measured by the use of biotinylated CMV-reactive monkey IgG and peroxidase-conjugated avidin. The assay was evaluated in comparison with the CF test and was found superior both in terms of qualitative and quantitative detection of CMV antibodies. The results were uninfluenced by the presence in the sera of rheumatoid factor or autoantibodies (antinuclear antibodies). A characteristic feature of this inhibition immunoassay was the absence of equivocal results as demonstrated by analysis of 500 donor sera which were classified in two distinct separate groups: reactive and nonreactive. The assay is simple and reproducible and provides for a good reagent economy. Crude antigen can be used without sacrifice of specificity. Antigen from one Roux bottle proved sufficient for 25,000 duplicate tests.

Animals↗

Isolation and adaptation characteristics of hepatitis A virus in primary African green monkey kidney cells: production of antigen useful for ELISA serology.

Four strains of hepatitis A virus (HAV) were isolated from four fecal samples of patients with type A hepatitis by using primary African green monkey kidney (PAGMK) cells or FRhK-4 cells. In all four samples viral antigen became detectable in PAGMK cells at the 3rd passage level after 9 weeks of incubation; detectable levels of antigen were reached earlier in FRhK-4 cells. An enzyme-linked immunosorbent assay (ELISA) was used to detect HAV antigen (HAV-Ag). Blocking experiments with negative and positive human sera and with paired marmoset sera established the identity of the virus. Infectious virus appeared to be both intracellular and extracellular. Although HAV-Ag could not be detected in culture medium by ELISA, the HAV infectivity titers of culture media were as high as those of cell-associated viruses (greater than 10(6) TCID50/0.2 ml). The passage procedure was simplified by using only virus isolated from cell-free medium as seed material, and the HAV strains were successfully propagated for 12 consecutive passages through PAGMK cells at 2-week intervals. The tissue-culture-produced HAV-Ag proved to be useful as a source of antigen in ELISA for detection of human anti-HAVIgG and IgM. The HAV strains adapted to PAGMK cells lost or decreased their ability to grow in FRhK-4 cells, while one strain adapted to FRhK-4 cells grew equally well in both cell systems.

Acclimatization↗

Laboratory diagnosis of herpesviruses.

Laboratory diagnosis is made either by demonstration of the presence of virus, viral antigens or virus-specific nucleic acid sequences in suitable specimens or by measurement of antibodies--rise in titer or presence of viral-specific IgM--in blood samples from the patients. A number of biological features characteristic for the herpes viruses can be utilised for detection: the infectivity (isolation in tissue culture), the morphology (visualisation by electronmicroscopy), the antigenicity of viral specified proteins produced by infected cells (immunofluorescence, ELISA and RIA), and unique sequences in viral DNA (hybridisation). The different methods are described and evaluated in regard to viral detectability and speed of performance. Concerning diagnostic serology only the ELISA systems for measurement of viral-specific IgG, total antibodies and IgM have been described because these methods now have been introduced in most viral diagnostic laboratories, and many commercial available kits also operate according to these techniques.

Antibodies, Viral↗

Virus-associated cancers in Greenland: frequent hepatitis B virus infection but low primary hepatocellular carcinoma incidence.

The incidence of primary hepatocellular carcinoma (PHC) in Greenland between 1960 and 1981 was determined and compared with the rate of this disease in Denmark. The annual age and sex rate (per 100,000) was not significantly different (overall, 1.9 vs. 2.2) despite a large difference in the prevalence of hepatitis B surface antigen (HBsAg) and anti-HBs markers of hepatitis. On the basis of a recent report of a very strong risk of PHC among male HBsAg carriers, 4.0 cases of PHC per year were expected in male Eskimos, but only 0.2 cases per year were observed. The incidence rates of other cancers suggested to be virally associated, including nasopharyngeal carcinoma, salivary gland cancer, and carcinoma of the cervix, were all high in Greenland compared to rates for the Danish population, and these high incidence rates are in accord with the markedly higher prevalences in Greenland Eskimos of viruses with which these other cancers have been associated. Thus Greenland Eskimos do not have a high incidence of PHC despite a high prevalence of HBsAg carriers, which suggests that other carcinogenic factors in this environment may be absent or that protective factors are present.

Carcinoma, Hepatocellular↗

IgA antibodies to herpes simplex virus type 1 in duodenal juice and saliva from patients with peptic ulcer and non-ulcer controls.

Fasting duodenal juice and saliva were obtained from 26 peptic ulcer patients and 28 controls. IgA antibodies to herpes simplex virus type 1 (HSV-1) were measured by the indirect enzyme-linked immunosorbent assay (ELISA). Total IgA in the samples was measured by the double-sandwich ELISA. The median and interquartile range of anti HSV-1 IgA titres in saliva were 8 (4-12) and 4 (1-8) in ulcer patients and controls, respectively (p less than 0.02). Comparative values in duodenal juice were 12 (2-16) and 4 (0-6) (p less than 0.002). The concentration of total IgA was not higher in ulcer patients than in controls, and no correlation existed between total IgA and anti HSV-1 titres. The results add further evidence that HSV type 1 is involved in the pathogenesis of peptic ulceration.

Adult↗

Antibodies to herpes simplex and Epstein-Barr viruses in Faroese children: association with sibship size, height and age.

Antibody to herpes simplex virus (HSV) type 1 and Epstein-Barr virus (EBV) capsid antibody were determined in 333 children from the Faroe Islands, aged 4, 8 and 13 years. An analysis of multi-way frequency tables was performed, testing seropositivity for each virus against combinations of the following variables: sibship size, birth order, mother's age at birth, birth weight, actual height and weight, age and sex. HSV-seropositivity was associated to sibship size, height and age, while EBV-seropositivity was related only to age.--It is discussed how the findings fit into epidemiological patterns described for Hodgkin's disease and multiple sclerosis, which are both supposed to be of viral origin. Our results suggest that HSV, but not EBV, may be among the candidates to be considered.

Adolescent↗

Lifestyle and antiviral antibody studies among homosexual men in Denmark.

Two-hundred and fifty-nine male homosexuals (HS) of a large and a small Danish town were studied for antibodies to various virus and their statistical relationship to sex habits, drug use and other lifestyle factors. Prevalence rates against cytomegalovirus (CMV) were 86.7% of HS men from Copenhagen and 73.3% of HS men from the smaller community of Aarhus, against 30% of a control group. Antibody prevalence in homosexuals was significantly related to number of years of homosexual activity (p less than 0.0001), number of partners (p less than 0.01), nitrite inhalant use in the past year (p less than 0.01), and independently to venereal disease during the past year (p less than 0.01). Titer levels correlated with number of years of HS activity (p less than 0.001), number of partners (p less than 0.01), and independently with nitrite use in the past year (p less than 0.01). The association between lifestyle and antibodies was not detectable for VCA-IgG, VCA-IgA, VCA-IgM, and EA antibodies to Epstein-Barr virus (EBV) or for antibodies to herpes simplex virus type 1 and type 2, parvovirus and rotavirus. In a subset of 78 HS men, T-helper/T-suppressor ratio was determined. No correlation was found between level of ratio and either prevalence or titer of antibodies against CMV, EBV-components or herpes type 1 and 2.

Acquired Immunodeficiency Syndrome↗

Hodgkin's disease: in vitro susceptibility of skin fibroblasts to infection with virus and to lysis by autologous lymphocytes.

Fibroblast cultures established from the skin of 16 untreated stage 1 and stage 2 Hodgkin's patients (HD) and 60 healthy controls were studied in their 3rd, 4th and 5th in vitro passage. HD cultures were similar to control cultures with respect to transformation with Simian sarcoma virus (SSV) and SV40 and with respect to interferon release. HD cultures, however, showed a depressed replication of both herpes simplex virus (HSV) type 1 and type 2. Preliminary evidence for enhanced immune interaction with fibroblasts in HD was a more frequent injury of HD than control fibroblast cultures when incubated 4 hours with autologous mononuclear leucocytes in the presence of autologous serum.

Adolescent↗

Intratypic differentiation of poliovirus strains by enzyme-linked immunosorbent assay (ELISA): poliovirus type 1.

A double antibody sandwich-ELISA has been developed for the detection of antigenic differences between wild and vaccine derived strains of Poliovirus type 1. Poliovirus strains antibodies were prepared in rabbits by immunization with virus suspensions of: Sabin LSc2ab (vaccine derived) and Brunhilde and Mahoney (wild types). IgG fractions were purified from antiserum by precipitation with ammonium sulphate and DEAE-Sephadex A50 chromatography. Purified IgG antibodies were used for coating of microtest plates (catching antibodies). The same reagents labeled with horseradish peroxidase were used as conjugates (detecting antibodies). Detecting antibodies were made strain specific by cross-absorption with the heterologous virus strain. Absorbed and non-absorbed detecting antibodies were subsequently used for detection and quantitation of the poliovirus antigen(s) bound to IgG-coated surfaces. Poliovirus laboratory strains and isolates from sixty-six individuals were differentiated intratypically as vaccine derived or wild types when the ELISA was performed using absorbed conjugates. No intermediate strains were found, and all clinical samples tested fell in two distinct categories. Conversely, when detecting antibodies were used before absorption a high degree of homology between wild and vaccine strains was demonstrated and the differentiation between the two groups was poorly achieved. The ELISA has been optimized in terms of specificity and sensitivity. Less than 10 ng of poliovirus antigens could be detected by non-absorbed detecting antibodies whereas 18 ng was the minimal amount detected by the same antibodies after absorption. Preparation of strain specific antibodies did not require a previous concentration of the poliovirus suspension used for the absorption. It is proposed that the developed ELISA is capable of: 1) detection of low amounts of poliovirus antigens in clinical samples, and 2) intratypic differentiation of poliovirus antigens as either vaccine derived or wild types.

Antibodies, Viral↗

Herpes simplex virus type-specific antibodies detected by indirect and competition ELISA. Comparison of sera from patients with carcinoma of the uterine cervix, age matched controls and patients with recurrent genital herpes.

A total of 85 human sera (32 from patients with carcinoma of the uterine cervix, 32 from matched controls, and 21 from patients with recurrent genital herpes) were tested in two different ELISAs for detection of HSV type-specific antibodies. The prevalence of HSV type 2 specific antibodies in the three groups were 69, 37 and 71% respectively. The prevalence of HSV type 1 specific antibodies in the three groups were 88, 75 and 76% respectively. Analysis of IgG and total antibodies gave identical results.

Antibodies, Viral↗