Structural and functional cardiac adaptations to a 10-week school-based football intervention for 9-10-year-old children.

The present study investigated the cardiac effects of a 10-week football training intervention for school children aged 9-10 years using comprehensive transthoracic echocardiography as a part of a larger ongoing study. A total of 97 pupils from four school classes were cluster-randomized into a control group that maintained their usual activities (CON; two classes, n = 51, 21 boys and 30 girls) and a football training group that performed an additional 3 × 40 min of small-sided football training per week (FT; two classes, n = 46, 23 boys and 23 girls). No baseline differences were observed in age, body composition, or echocardiographic variables between FT and CON. After the 10-week intervention, left ventricular posterior wall diameter was increased in FT compared with CON [0.4 ± 0.7 vs -0.1 ± 0.6 (± SD) mm; P < 0.01] as was the interventricular septum thickness (0.2 ± 0.7 vs -0.2 ± 0.8 mm; P < 0.001). Global isovolumetric relaxation time increased more in FT than in CON (3.8 ± 10.4 vs -0.9 ± 6.6 ms, P < 0.05) while the change in ventricular systolic ejection fraction tended to be higher (1.4 ± 8.0 vs -1.1 ± 5.5%; P = 0.08). No changes were observed in resting heart rate or blood pressure. In conclusion, a short-term, school-based intervention comprising small-sided football sessions resulted in significant structural and functional cardiac adaptations in pre-adolescent children.

RTS,S malaria vaccine efficacy and immunogenicity during Plasmodium falciparum challenge is associated with HLA genotype.

Although RTS,S remains the most advanced malaria vaccine, the factors influencing differences in vaccine immunogenicity or efficacy between individuals or populations are still poorly characterised. The analyses of genetic determinants of immunogenicity have previously been restricted by relatively small sample sizes from individual trials. Here we combine data from six Phase II RTS,S trials and evaluate the relationship between HLA allele groups and RTS,S-mediated protection in controlled human malaria infections (CHMI), using multivariate logistic or linear regression. We observed significant associations between three allele groups (HLA-A∗01, HLA-B∗08, and HLA-DRB1∗15/∗16) and protection, while another three allele groups (HLA-A∗03, HLA-B∗53, and HLA-DRB1∗07) were significantly associated with lack of protection. It is noteworthy that these 'protective' allele groups are thought to be at a lower prevalence in sub-Saharan African populations than in the UK or USA where these Phase II trials occurred. Taken together, the analyses presented here give an indication that HLA genotype may influence RTS,S-mediated protective efficacy against malaria infection.

Correlation between carbohydrate structures on the envelope glycoprotein gp120 of HIV-1 and HIV-2 and syncytium inhibition with lectins.

The binding of 13 different lectins to gp120 partially purified from two HIV-1 isolates and one HIV-2 isolate was studied by in situ staining on electrophoretically separated and electroblotted HIV antigens. The lectins concanavalin A, wheat germ agglutinin, Lens culinaris agglutinin, Vicia faba agglutinin, Pisum sativum agglutinin and phytohaem(erythro)agglutinin bound to gp120 of all three isolates. The carbohydrate of gp120 recognized by lectins was thus arranged in at least four types of glycans: a high mannose type glycan, a bisected hybrid or complex type glycan, a biantennary fucosylated complex type glycan and a triantennary bisected complex type glycan. Only lectins which bound at least one of the four types of glycans were capable of inhibiting fusion of HIV-infected cells with CD4 cells by a carbohydrate-specific interaction with the HIV-infected cells. Thus, several different glycan structures may be implicated in CD4-gp120 binding.

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.

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.

Derivatives of amphotericin inhibit infection with human immunodeficiency virus in vitro by different modes of action.

Three water-soluble derivatives of amphotericin B were tested for inhibition of HIV infection in vitro. The compounds amphotericin B methyl ester (AME) and N-(N'-(2-(4'-methylmorpholinio)ethyl)N"-cyclohexyl guanyl) amphotericin B methyl ester (MCG) inhibited HIV infection by 50% at 1 microgram/ml; N-(N'-(3-dimethylaminopropyl)N"-ethyl guanyl) amphotericin B (DAPEG) did so at 5-11 micrograms/ml. While the virus-inhibitory effect of AME was due to an interaction with target lymphocytes, the effect of MCG was due to a direct anti-viral action. AME increased the potential of infected cells to fuse with uninfected cells, but MCG had no significant effect on cell fusion. All compounds had a lower cellular toxicity than amphotericin B and were not toxic at concentrations below 20 micrograms/ml.

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.

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.

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.

[Male sterilization with vasectomy. The effect of the operation on sex life]. / Mandlig sterilisation med vasektomi. Indgrebets indflydelse på det seksuelle samliv.

PIP: 182 of 220 men, 25-54 years of age, who underwent vasectomy, filled out a questionnaire describing how the operation affected their sex life. Nearly all of the men were married and were regularly employed. 86% of those who returned the questionnaire had 2 or 3 children. 99% said that their wives agreed with their decision to undergo vasectomy. 80% chose vasectomy because their wives could not or did not want to use oral contraceptives or other methods, or because they wanted 100% effectiveness. 48 experienced short-term difficulties. 6% reported a decrease in libido or orgasm, and 1% reported a decrease in sexual intercourse after the operation. 86% would recommend the operation to others, 7% would not.^ieng

[Pneumococcal bacteremia in Hvidovre Hospital 1986-1990]. / Pneumokokbakteriaemi på Hvidovre Hospital 1986-1990.

The study describes 156 consecutive cases of pneumococcal bacteraemia among patients admitted to Hvidovre Hospital during the five-year period 1986-1990. Pneumococcal bacteraemia was most common in the age groups 0-4 and 50-99 years. The most common focus of infection was the lungs (84%). 81% had preexisting diseases and the most common were: Immunosuppression due to drugs, alcoholism, cardiovascular disease, chronic obstructive lung disease, diabetes and myelomatosis. Patients over 65 years of age had a higher case fatality (35%) than younger (12%). The overall case fatality rate was 24%. Twenty-three percent of cases were hospital-acquired, and associated with a case fatality of 37%. Pneumococcal bacteraemia was most common during the winter season and unrelated to influenza. Eighty-four percent of the examined isolates represented capsular types included in the 23-valent pneumococcal vaccine. Three percent of the tested strains were relatively resistant to penicillin (MIC > 0.1 microgram/ml). Despite antibiotic treatment, the mortality from pneumococcal bacteraemia, particularly in elderly, remains high. With this in mind, one may consider offering pneumococcal vaccination to persons over 65 years of age with chronic predisposing diseases.

[A mini epidemic of varicella zoster virus reinfection at a department of hematology]. / Miniepidemi af varicel zoster virus reinfektion på en haematologisk afdeling.

Whereas primary infection with varicella zoster virus (VZV) (chickenpox) and reactivation of VZV (shingles) are common and recognized, clinical reinfection with VZV is rare. A little epidemic of presumed reinfection with VZV in six immune-compromised adults is presented here. The epidemic lasted for three months, during which a healthy young woman also developed a primary VZV infection in the form of chickenpox. In the immune-compromised patients, the clinical picture was dominated by disseminated, prolonged and frequently haemorrhagic and necrotic eruptions which may cause diagnostic difficulties. Skin biopsy proved helpful in the diagnosis while demonstration of the VZV antigen in the skin elements was specific and sensitive. All of the patients, with one exception, were treated with acyclovir and dissemination of the infection to the inner organs did not occur. One patient may have died on account of the VZV infection. In conclusion, immune-incompetent patients must be warned against infection from chickenpox or disseminated herpes zoster. In cases of proved exposure, prophylactic treatment with acyclovir should be considered and, in cases of clinical disease, immediate treatment with 10 mg acyclovir per kg body weight should be administered intravenously thrice daily.

[Survival of patients with zidovudine resistant HIV]. / Patientoverlevelse ved zidovudinresistent HIV.

The survival of 35 patients with AIDS or advanced HIV infection on zidovudine treatment was related to the viral sensitivity to the drug and to the CD4+ cell count. Fourteen 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.

HIV antigen stimulates basophil leukocytes from AIDS patients to release histamine due to type I allergy.

HIV antigen-induced histamine release was examined in leukocyte suspensions from 12 patients with AIDS and 10 healthy controls. Nine of the twelve patients released histamine, while no release was obtained in cells from the control group. The mechanism was examined by removal of immunoglobulins (Ig) from the patient cells before stimulation with HIV antigen, which resulted in an abolition of the histamine release. Transfer of the Ig to cells from normal individuals rendered these cells able to respond to HIV. The removal and fixation of Ig were followed by disappearance and reappearance of the response to anti-IgE. These findings indicate that the histamine release by HIV is caused by a type I (IgE-mediated) reaction.

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.

Comparison of four serological tests for the detection of specific immunoglobulin M in cord sera of infants congenitally infected with cytomegalovirus.

Four serological tests (3 immunoassays using enzyme-labelled antigen and 1 radioimmunoassay) were compared as regards the detection of cytomegalovirus (CMV) immunoglobulin M in cord sera. 68 cord sera from infants congenitally infected by CMV were included in the study. The infections were primarily diagnosed by virus isolation close to birth. Four laboratories in 3 countries were involved, each laboratory using its own or a commercial test. Of the sera tested in the different laboratories 50-80% were found to be reactive. Both qualitatively and quantitatively there was a good correlation between the 3 enzyme-immunoassays. The RIA results differed to some extent from the enzyme tests as regards the quantification of IgM. The advantage of prospective IgM screening in undiluted cord sera followed by confirmatory virus isolation test in the neonatal period in IgM-positive cases is discussed.

HIV antigen-induced release of histamine from basophils from HIV infected patients. Mechanism and relation to disease progression and immunodeficiency.

Basophil leukocytes from 39 HIV-infected patients with various degrees of immunodeficiency and disease progression were stimulated with an HIV antigen preparation. Cells from 19 of 22 patients with AIDS and all of six patients with milder degrees of HIV-related disease showed significant histamine release. In contrast, cells from 11 asymptomatic HIV-infected patients and 11 healthy control persons released no histamine. The histamine release induced by HIV antigen was found to be inversely correlated to the number of CD4 positive T lymphocytes. These results indicate that the histamine release was related to both the clinical stage of disease and the degree of immunodeficiency. Passive sensitization experiments showed that IgE, but not IgG, was responsible for the induction of histamine release, indicating the reaction to be type 1 allergic. The histamine release caused by HIV might be involved in the development of disease because of the immunomodulating properties of this mediator.

Synthesis and evaluation of antiviral activity of L-acosamine and L-ristosamine nucleosides of furanose configuration.

Mercuric-catalyzed hydrolysis of acetylated L-rhamnal 1 gives an alpha,beta-unsaturated aldehyde 2. 1,4-Addition of DBU-phthalimide salt with concomitant acetyl shift resulted in L-ribo and L-arabino isomers of 5-O-acetyl-2,3,6-trideoxy-3-phthalimido-hexofuranose 3 and 4. After acetylation at the anomeric center, coupling with silylated thymine resulted in three new nucleosides, with L-acosamine and L-ristosamine of furanose configuration as the carbohydrate moiety. The target compounds have been evaluated for their antiviral activity against HIV and HSV-1.

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.