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Biomedical subjects

B F Vestergaard

Publications and source records attributed to B F Vestergaard.

At least 37 records · Page 2Linked to original sources
PubMed1992

Synthesis of pyranoid analogues of the anti-HIV active 3'-deoxy-2',3'-didehydrothymidine (D4T).

The primary hydroxy group of ethyl 2,3-dideoxy-alpha-D-erythro-hex-2-enopyranoside (1) was selectively protected and the secondary hydroxy group was deoxygenated via the dithiocarbonate 3 from which ethyl 6-O-(4-methoxybenzoyl)-2,3,4-trideoxy-alpha-D-glycero-hex-2-eno pyranoside (4) and its regioisomer (5) were produced. These were converted into didehydro nucleosides by glycosylation of silylated heterocyclic bases in the presence of trimethylsilyl trifluoromethanesulfonate as catalyst. The configurations of the anomeric products were assigned by 1H-NMR analysis of the corresponding saturated compounds which were obtained by hydrogenation of the double bond in the carbohydrate moiety. The compounds 9a,b,d, 10a,b, 14a,b,e,f, and 15a,b,e,f did not show any significant activity against HIV or HSV-1.

Animals↗
PubMed1992

Development of resistance to zidovudine in HIV strains isolated from CD4+ lymphocytes and plasma during therapy.

An assay based on production of HIV antigen in cultures of CD4+ lymphocytes infected 'in vitro' with cell-free virus was established. Using this assay it was possible to isolate, propagate and reliably determine the zidovudine susceptibility of HIV isolates from all patients despite differences in cellular tropism and syncytium inducing capacity. Using this assay, differences in zidovudine susceptibility of 52 serial isolates obtained from 16 patients before and after initiation of therapy were examined. HIV with a 10- to 100-fold reduced susceptibility to zidovudine were isolated from 13 patients as early as 4 months after initiation of therapy. Number of months of zidovudine treatment was strongly associated with development of viral resistance, and high CD4 cell counts tended to be associated with lower rates of development of resistance. That patients can harbor mixtures of virus strains with different susceptibility to zidovudine was confirmed by the differences in susceptibility between isolates obtained simultaneously from CD4+ lymphocyte and plasma, and by the differences in susceptibility between virus strains isolated from clones of CD4+ lymphocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Effect of isoprinosine on HIV antigenaemia.

OBJECTIVE: The objective of this study was to evaluate the effect of isoprinosine on HIV-antigen expression in HIV-positive patients without AIDS. DESIGN: Serum samples from anti-HIV-positive patients without AIDS participating in a double-blind, placebo-controlled trial of isoprinosine in the treatment of HIV infection were analysed for the presence of HIV antigen. SETTING: Data and samples were collected from the 21 medical centres who participated in the Scandinavian multicentre placebo-controlled isoprinosine study. PATIENTS, PARTICIPANTS: Samples were available from 19 of 21 participating centres. Of 866 patients who enrolled, baseline serum samples were available for 642 (74%; 308 isoprinosine- and 334 placebo-treated patients). INTERVENTIONS: Treatment was 1 g isoprinosine administered orally three times a day or matching placebo for 24 weeks. MAIN OUTCOME MEASURES: Comparison of HIV-antigen levels before and during treatment in both the isoprinosine-treated group and the placebo-treated group of patients. RESULTS: During the study, AIDS developed in 19 patients; 17 of whom were receiving placebo treatment and two isoprinosine. The proportion of HIV-antigen-positive patients developing AIDS during treatment was significantly different from the proportion of HIV-antigen-negative patients in whom AIDS developed (6 versus 2%; P = 0.02). No significant changes in HIV-antigen levels were observed between the isoprinosine- and the placebo-treated group of HIV-antigen-positive patients. Median HIV-antigen levels did not change significantly in either the isoprinosine- or the placebo-treated group. CONCLUSION: Our results suggest that isoprinosine does not have antiviral activity against HIV in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Trend towards decreased survival in patients infected with HIV resistant to zidovudine.

The survival of 35 patients with AIDS or advanced HIV infection on treatment with zidovudine was related to the viral sensitivity to the drug and to the CD4+ cell count. 14 patients died, the survivors were followed up for an average of 804 days. In a univariate Cox model, survival was strongly related to log IC90 (p = 0.0003) and to the CD4+ count (p = 0.0002). In a bivariate model, log IC90 and the CD4+ count contributed to the prediction of survival (p = 0.12 and 0.06, respectively). Large studies of combination or alternation therapy with several anti-HIV drugs should be given high priority.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Case-control study of risk factors for cervical neoplasia in Denmark. I: Role of the "male factor" in women with one lifetime sexual partner.

Possible risk factors for cervical cancer were investigated in 645 women, 20-49 years of age from Copenhagen, with histologically confirmed cervical cancer or carcinoma in situ and in 614 controls drawn at random from the female population of the same area. To study the role of the "male factor", monogamous cases and controls together with their husbands were invited for further examination. This included a personal interview, a blood sample for analysis of herpes simplex virus antibodies, and a penile swab for papillomavirus analysis. In total, 41 case couples and 90 control couples were enrolled (89% and 92% of eligibles, respectively). The most significant risk determinants were a history of genital warts in the male (RR = 17.9 for ever vs. never) and ever having used condoms (RR = 0.2). Other potentially important factors, although not statistically significant, were ever having visited prostitutes (RR = 2.6, p = 0.14), circumcision (RR = 0.3, p = 0.18), and a history of genital warts in the female (RR = 4.6), p = 0.09). Having a husband with a history of multiple sexual partners was also associated with an increased crude risk, but when adjustment was made for husband ever having had genital warts, use of condom, and age, no significant excess risk was observed. Human papillomavirus DNA, which was tested for with ViraPap and ViraType, was detected in one of the controls, and in only 2 case husbands. This study points to the importance of "high-risk males" for the development of cervical cancer in their sexual partner; the results support the infectious nature of the disease.

Adult↗
PubMed1991

Isolation of HIV from cultures of purified CD4+ lymphocytes.

Isolation of HIV from cultures of CD4+ lymphocytes purified from peripheral blood by indirect panning was optimized and evaluated. Infectious HIV was isolated by single isolation attempts in 98% of 102 HIV-antibody-positive patients (55 had AIDS or ARC and 47 were clinically healthy). The average culture time required for positive cultures was largely independent of the CD4 count of the patients and 87% of the positive isolation cultures from both groups of patients became positive within 14 days of culture. An evaluation of the possible influence of media additives on propagation of HIV showed that: amphotericin-B had a suppressive effect on HIV replication at concentrations recommended for anti-fungal activity; recombinant and human interleukin-2 were equally suitable for both isolation cultures and for propagation of HIV, and polybrene, at a concentration of 2 micrograms/ml in the culture medium had a beneficial effect.

Amphotericin B↗
PubMed1991

Effect of selected neuroleptic agents and stereo-isomeric analogues on virus and eukaryotic cells.

Chlorpromazine, cis(Z)-chlorprothixene (Truxal), and the non-neuroleptic trans(E)-chlorprothixene and trans(E)-flupenthixol were studied in vitro for possible antiviral effect on Herpes simplex virus 2 and for toxic effect on human diploid fibroblasts. Based on an enzyme-linked immunosorbent assay (ELISA) antiviral activity was demonstrated for all the compounds in the concentration range 0.39 micrograms/ml-25 micrograms/ml. A cell-toxic effect was shown in the higher concentration range for all the compounds except cis(Z)-chlorprothixene. A cell-stimulatory effect was also detected at the lower concentration range (about 3.13 micrograms/ml) for all compounds. Thus both cell stimulation and antiviral effect can be found for the same agent within the same concentration range. The results point to the possibility of creating different antiviral drugs--which would also include a cell-stimulatory activity--among psychopharmacological drugs and their stereoisomeric analogues.

Antipsychotic Agents↗
PubMed1991

Inhibition of human immunodeficiency virus 1 (HIV-1) and herpes simplex virus 1 (HSV-1) infectivity with a broad range of lectins.

Five lectins with specificity for N- and O-linked oligosaccharides were examined for inhibition of HIV-1 and HSV-1 infectivity in vitro. HIV-1 isolate HTLVIIIB was preincubated with lectin and subsequently inoculated onto MT-4 cells. Lectins specific for N-linked oligosaccharides blocked HIV infection in nanomolar-micromolar concentrations, but no anti-HIV effect was found with the lectin HPA, mainly reacting with O-linked oligosaccharides. HSV-1 infectivity was measured in a plaque reduction assay using Vero cells, and while both N- and O-linked oligosaccharide -specific lectins inhibited HSV-1 infection, the most potent inhibition was found with the lectin HPA. These results indicate that lectins may have a broad antiviral effect on enveloped viruses only limited by types of oligosaccharides present on individual viruses.

Animals↗
PubMed1991

Prevalence of HIV infection in seronegative high-risk individuals examined by virus isolation and PCR.

HIV seronegative individuals with high-risk behavior were tested for HIV infection by sensitive virus isolation techniques using T4 lymphocytes and monocyte/macrophages, and by detection of proviral DNA using PCR with three different sets of nested primers. No evidence of HIV infection was found among the 31 seronegative high-risk subjects, either by virus isolation of by PCR (97.5% confidence limits, 0-11). Our results indicate that ongoing HIV infection in seronegative persons at high risk of infection is a rare event.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Oral candidiasis and hairy leukoplakia correlate with HIV infection in Tanzania.

We report a detailed study on oral lesions and their association with the WHO revised provisional case definition of AIDS as well as serologic signs of HIV infection among 186 patients in Dar Es Salaam, Tanzania. The patient material consisted of 39 hospitalized suspected AIDS patients, 44 medical nonsuspected patients, 53 dental outpatients, and 50 patients with sexually transmitted diseases. The male:female ratio was 2.1:1 on average. Oral examination was done without knowledge of the HIV status of the patients. Among 39 suspected AIDS patients 97% had WHO AIDS criteria and 90% were seropositive for HIV. Among the 147 patients not suspected of having AIDS 18 (12%) had AIDS criteria and 15% had serologic evidence of HIV infection. The presence of WHO AIDS criteria correlated significantly with the presence of HIV antibodies, but not with HIV antigen. Oral lesions were found in 54% of those with AIDS criteria and 52% of HIV-infected patients, as compared to 3% and 6% of the patients without AIDS criteria and HIV infection, respectively (p less than 0.01). Among patients with AIDS atrophic candidiasis occurred in 21%, pseudomembranous candidiasis in 23%, hairy leukoplakia in 36%, herpetic stomatitis in 2%, Kaposi's sarcoma in 4%, and nonspecific ulcer in 4%. The presence of oral lesions had a high predictive value for presence of AIDS criteria as well as for presence of HIV infection in this hospital setting. All patients should have a thorough oral examination and the presence of the aforementioned oral lesions should lead to testing for HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Risk factors for cervical human papillomavirus and herpes simplex virus infections in Greenland and Denmark: a population-based study.

Risk factors for genital human papillomavirus (HPV) types 6/11 and 16/18 and any HPV type as well as for herpes simplex virus type 2 (HSV-2) infections were investigated in a population-based study of 1,600 randomly selected women (20-39 years) from Godthåb (native, Nuuk), Greenland, and Nykøbing Falster, Denmark. A total of 586 Greenlandic women and 661 Danish women were included, respectively. They all had a personal interview and a gynecologic examination with cervical smear and swab for HPV analysis (filter in situ hybridization). Moreover, a blood sample was obtained for analysis for HSV-2 antibodies by enzyme-linked immunosorbent assay. In view of the general concept of HPV as a sexually transmitted virus, it is unexpected that women with "multiple" partners revealed a significantly lower risk for all types of HPV than did women with "few" partners, the odds ratio (OR) being 40-60% decreased in women with greater than or equal to 30 partners compared with women who had 0-4 sexual partners. In contrast, the risk for HSV-2 infection was significantly increased among women with early age at first sexual intercourse (OR = 2.9 for age less than or equal to 13 vs. 14-16 years) and multiple partners (OR = 2.6 for greater than or equal to 20 vs. 0-4 partners) (hereafter referred to as "high sexual activity" as well as with an increasing number of sexually active years with an unprotected cervix (i.e., without the use of barrier contraceptives) (OR = 2.0 for greater than or equal to 15 vs. 0-9 years). The results of this study thus demonstrate a surprising risk pattern for HPV types 6/11 and 16/18, but a pattern for HSV-2 in line with that to be expected for a sexually transmitted virus. This could indicate the existence of factors, especially in women with high sexual activity, which interfere with the expression of HPV or with the ability to detect it and/or that HPV may be transmitted by means other than sexual contact.

Adult↗
PubMed1990

Long-term suppression of severe recurrent genital herpes simplex infections with oral acyclovir: a dose-titration study.

Twenty immunocompetent patients, four females and 16 males, with severe recurrent genital herpes (median number of recurrences the previous year 16, range (8-24] entered an open continuous long-term suppressive treatment with oral acyclovir (ACV) for 12 months. The study included a dose-titration schedule: (ACV, 200 mg x 4/1-3 months, ACV, 400 mg x 2/4-6 months, ACV, 200 mg x 2/7-9 months, and ACV, 400 mg x 1/10-12 months). Patients with recurrences on steps two and three received an alternative dose of ACV, 200 mg x 3. Otherwise patients entered the previous dose-step. Five (20%) of patients were completely free of symptoms (recurrences and abortive lesions) during the four dose-reduction periods. A further nine patients (50%) could be dose-reduced to 200 mg x 3 without symptoms. Isolates from three patients showed a decrease in virus sensitivity after ceasing treatment. In conclusion, 14/20 of treated patients could be dose reduced to 200 mg x 2-3 without selection of HSV strains showing clinically important decreases in sensitivity towards ACV.

Acyclovir↗
PubMed1990

Abnormal Papanicolaou smear. A population-based study of risk factors in Greenlandic and Danish women.

Possible risk factors for abnormal Papanicolaou smear were investigated in a population-based cross-sectional study. From Nuuk (Greenland) and Nykøbing Falster (Denmark), random samples of 800 women aged 20-39 years were drawn. Totals of 586 and 661 women were included in Greenland and Denmark, respectively. All women went through a personal interview, and had a gynecologic examination including a PAP smear and cervical swab for HPV analysis. A blood sample was taken for analysis of HSV type specific antibodies. Multiple sexual partners was the most important risk factor for abnormal cervical cytology (OR = 4.2). An infectious etiology was also indirectly supported by a relatively protective effect of barrier contraceptive methods (OR = 0.6). The simultaneous finding of HPV 16/18 as a significant risk factor (OR = 2.4) cannot be taken uncritically as support for a causal effect of this HPV type, since such a relationship between cytological changes of the cervix and HPV infection could also emerge if the positive PAP smear was not just a measure of intra-epithelial neoplasia but also an expression of the infection itself on the cervix.

Adult↗
PubMed1989

Risk factors for cervical cancer in Greenland and Denmark: a population-based cross-sectional study.

The incidence of cervical cancer in Greenlandic women aged 20-39 years is nearly 6 times higher than in Danish women of the same age. Possible determinants of cervical cancer incidence were investigated in a population-based cross-sectional study. 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 studied in Greenland and Denmark, respectively. All underwent a personal interview. In Greenland, 13% of the women reported first intercourse before the age of 14 in contrast to 3.5% in Denmark, and nearly 85% of the Greenlanders had their sexual debut before the end of the 16th year of age whereas this applied to only 45% of the Danish women. The prevalence of women with 0-1 lifetime sexual partner was 20.4% in Denmark, and only 1.7% in Greenland. In contrast, 53.2% of the Greenlandic women reported more than 20 partners and 22.4% more than 40 partners. The corresponding figures for Denmark were 3.6% and 0.3%, respectively. In Greenland the most common contraceptive method was the use of intra-uterine devices (73.6%), whereas, in Denmark, oral contraceptive use was most frequent (87.9%). Few Greenlanders had ever used "barrier" contraceptives (diaphragm: 1.4%; condom: 18.1%) compared to Denmark (diaphragm: 10.1%; condom: 53.9%). As many as 87.4% were current smokers in Greenland (Denmark: 53.6%) and 5.6% claimed to have never smoked, whereas this applied to 35.3% in Denmark. The indications of a higher sexual activity (multiple partners, early age at first intercourse) in Greenland compared to Denmark are in line with the observed higher rates of sexually transmitted diseases and with the hypothesis that differences in cervical cancer incidence between Greenland and Denmark are determined by aspects of sexual background.

Adult↗
PubMed1989

Isolation of HIV using T-lymphocyte 'panning': methodological aspects.

A technique for isolation of HIV using selective cultures of T4 cells obtained from peripheral blood by immunochemical separation was developed and optimized. Using this method infectious virus could be isolated in single isolation attempts from 89% of 35 HIV-infected patients in different stages of immunodeficiency. This isolation frequency was virtually independent of the stage of the disease, in contrast to the results obtained by the conventional isolation technique based on peripheral mononuclear cells (PMC). It is concluded that isolation of HIV from selected T4 cells is superior to other methods when isolation is attempted from healthy HIV-infected individuals.

Antibodies, Monoclonal↗
PubMed1989

The incidence of herniated disc and varicella zoster virus infection in lumboradicular syndrome.

121 patients suffering from lumboradicular syndrome were examined for the presence of varicella zoster virus (VZV) infection. Lumbar myelography was carried out on all. VZV-antibody determination in blood, as well as in spinal fluid, was by indirect ELISA. In 40% of cases lumbar myelography revealed no signs of a herniated disc; none had raised antibody titre in spinal fluid. VZV-antibody titre in blood indicated VZV infection in only 3.

Antibodies, Viral↗
PubMed1989

Antigen-antibody reaction in solution in capture competition immunoassay for human immunodeficiency virus antibodies.

In the capture competition immunoassay, undiluted serum was reacted in solution with purified human immunodeficiency virus (HIV) antigen in wells of microtest plates coated with anti-HIV immunoglobulin G antibodies (HIV capture antibodies). HIV antibodies present in the serum being tested combined with the HIV antigen and thus blocked (completely or partially) the fixation of the antigen to the capture layer. Unblocked antigenic activity was measured in subsequent steps by the use of biotinylated anti-HIV immunoglobulin G and peroxidase-conjugated avidin. The assay was evaluated in comparison with indirect enzyme-linked immunosorbent assay and Western (immuno-) blot (WB). A total of 180 serum samples which reacted repeatedly as positive in indirect enzyme-linked immunosorbent assay but negative in WB were found to be negative by the capture competition assay. Of 54 serum samples showing dubious reactions (single p24 bands in WB), 53 were clearly separated into positive or negative reactions, whereas 1 serum sample gave a borderline reaction. It was concluded that a characteristic feature of this kind of inhibition assay is a very low frequency of equivocal results.

AIDS Serodiagnosis↗