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The triphosphorylated form of the nucleoside analogue 3'-azido-3'-deoxythymidine (Zidovudine, AZT) is claimed to interrupt the HIV replication cycle by a selective inhibition of viral reverse transcriptase, thereby preventing the formation of new proviral DNA in permissive, uninfected cells. Given that initial HIV infection of an individual instigates abundant HIV replication from inception until death, and that the life of infected T-cells is only several days, the administration of AZT should lead both in vitro and in vivo (i) to decreased formation of proviral DNA; and thus (ii) to decreased frequencies of 'HIV isolation' (detection of p24 or reverse transcription or both) in stimulated cultures/cocultures of T-cells from seropositive individuals; (iii) to decreased synthesis of HIV p24 and RNA ('antigenaemia', 'plasma viraemia', 'viral load') ultimately resulting in low or absent levels of all three parameters; and (iv) to a perfect and direct correlation between all these parameters. A critical analysis of the presently available data shows that no such evidence exists, an outcome not unexpected given the pharmacological data on AZT. HIV experts all agree that only the triphosphorylated form of AZT (AZTTP) and not the unphosphorylated form administered to patients, nor its mono- or diphosphate, is the active agent. Furthermore, the mechanism of action is the ability of AZTTP to halt the formation of HIV-DNA (chain termination). However, although this claim was posited from the outset, AZT underwent clinical trials and was introduced as a specific anti-HIV drug many years before there were any data proving that the cells of patients are able to triphosphorylate the parent compound to a level considered sufficient for its putative pharmacological action. Notwithstanding, from the evidence published since 1991 it has become apparent that no such phosphorylation takes place and thus AZT cannot possess an anti-HIV effect. However, the scientific literature does elucidate: (i) a number of biochemical mechanisms which predicate the likelihood of widespread, serious toxicity from use of this drug; (ii) in vitro data proving that AZT has significant antibacterial and antiviral properties which confound interpretation of its effects when administered to patients. Based on all these data it is difficult if not impossible to explain why AZT was introduced and still remains the most widely recommended and used anti-HIV drug.

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The existence of specific antibody/protein reactions is the crucial assumption underlying proof of HIV isolation, proof of HIV infection and the causative role of HIV in AIDS. However, since 1. antibodies which react with the 'HIV' proteins arise following allogenic stimuli in non-HIV-infected animals and humans, as well as in mice and humans with autoimmune disorders; antibodies to antigens from both mycobacteria and yeasts cross-react with HIV env and gag proteins; 2. individuals belonging to the AIDS risk groups are subjected to allogenic stimuli and have high levels of autoimmune antibodies, while the vast majority of patients in the AIDS risk groups are infected with either or both mycobacteria or yeasts; the evidence for the existence of HIV and its putative role in AIDS must be reappraised.

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The data generally accepted as proving the HIV theory of AIDS, HIV cytopathy, destruction of T4 lymphocytes, and the relationship between T4 cells, HIV and the acquired immune deficiency clinical syndrome are critically evaluated. It is concluded these data do not prove that HIV preferentially destroys T4 cells or has any cytopathic effects, nor do they demonstrate that T4 cells are preferentially destroyed in AIDS patients, or that T4 cell destruction and HIV are either necessary or sufficient prerequisites for the development of the clinical syndrome.

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In this review, the association between the Acquired Immune Deficiency Syndrome (AIDS) and haemophilia has been carefully examined, especially the data that have been interpreted as indicating transmission of the human immunodeficiency virus (HIV) to the recipients of purportedly contaminated factor VIII preparations. In our view, the published data do not prove the hypothesis that such transmission occurs, and therefore HIV cannot account for AIDS in haemophiliacs.

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The data widely purporting to show the existence and heterosexual transmission in Africa of a new syndrome caused by a retrovirus which induces immune deficiency are critically evaluated. It is concluded that both acquired immune deficiency (AID) and the symptoms and diseases which constitute the clinical syndrome (S) are of long standing in Africa, affect both sexes equally and are caused directly and indirectly by factors other than human immunodeficiency virus (HIV). Seropositivity to HIV in Africans usually represents no more than cross-reactivity caused by an abundance of antibodies induced by the numerous infectious and parasitic diseases which are endemic in Africa. The apparently high prevalence of 'AIDS' and 'HIV' seropositives is therefore not surprising and is not proof of heterosexual transmission of either HIV or AIDS.

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The binding of lectins to the trophoblast of rat blastocysts has been studied using quantitative ultrastructural cytochemistry. Rat blastocysts from early, mid and late d 5 of gestation were stained using biotinylated lectins (Phytolacca americana [Phy am], fucose binding protein [FBP] and soybean agglutinin [SBA]) and a sensitive avidin-ferritin cytochemical method. Electron micrographs of ferritin particles along the membrane were processed to produce images for which grey scale levels could be established and the ferritin particles automatically counted. The ferritin:membrane ratio was then calculated. Increased binding with Phy am (which detects short chain oligosaccharides) was found after midday of d 5, i.e. after hatching. Binding of FBP and SBA did not alter during the period studied. The increased concentration of oligosaccharides on the blastocyst surface membrane after hatching may have important implications for blastocyst attachment to the endometrium.

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It is currently accepted that a positive Western blot (WB) HIV antibody test is synonymous with HIV infection and the attendant risk of developing AIDS. In this communication we present a critical evaluation of the presently available data on HIV isolation and antibody testing. This evidence indicates that: (1) the antibody tests are not standardized; (2) the antibody tests are not reproducible; (3) the WB proteins (bands) which are considered to be encoded by the HIV genome and to be specific to HIV may not be encoded by the HIV genome and may in fact represent normal cellular proteins; (4) even if the proteins are specific to HIV, because no gold standard has been used to determine specificity, a positive WB may represent nothing more than cross-reactivity with non-HIV antibodies present in AIDS patients and those at risk. We conclude that the use of antibody tests as a diagnostic and epidemiological tool for HIV infection needs to be reappraised.

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Recently published informed debate affords strong indication that in patients with the Acquired Immune Deficiency Syndrome, HIV cannot, directly or indirectly, be the cause of Kaposi's sarcoma. This paper provides reasons for disallowing a current alternative theory that Kaposi's sarcoma is due to an unidentified sexually transmitted infectious agent and proposes instead that Kaposi's sarcoma is the result of prolonged and repeated exposure to nitrites and/or semen. If this alternative hypothesis is strengthened by confirmation of its predictions then the relationship of HIV to Kaposi's sarcoma, one of the principal AIDS-associated diseases, becomes somewhat remote. This may facilitate a shift of emphasis and encourage the development of alternative therapies.

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Carbohydrates were studied on the surface of uterine epithelial cells by lectin-avidin-ferritin histochemistry. The lectins, wheat germ agglutinin, fucose binding protein, soy bean agglutinin and the lectin from Phytolacca americana were used in the study. Statistically significant increases in three carbohydrates on day 6 of pregnancy--the day of blastocyst implantation--were found when compared with oestrus. These increases could contribute to the mechanism of blastocyst attachment to uterine epithelium.

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Freeze-fracture electron microscopy has been used to study tight junctions of epithelial cells in the rat fallopian tube. At oestrus, junctions were found to consist of strands parallel to the surface whereas at day 6 of pregnancy, junctions were deeper and extensively interconnected. We consider the involvement of ovarian hormones and the cross-tissue significance of our findings.

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Cytochemistry using biotinylated lectins and an avidin-ferritin label has been combined with freeze-fracture to study the relationship between surface carbohydrates and intramembranous particles in uterine epithelial cells. We find no structural relationship between the 2 classes of membrane components and consider the significance of this finding.

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The records of 90 consecutive adult patients, who presented after blunt abdominal trauma and who underwent diagnostic, percutaneous peritoneal lavage over a 3 year period, were reviewed. Lavage effluents were considered positive, negative or equivocal. An equivocal result was one where the tubing contained blood stained fluid, but it was still possible to see newsprint through the tubing. Fifty-one lavages were positive, 24 negative and 15 equivocal. All 51 patients with a positive effluent and three of the patients with an equivocal effluent had a laparotomy and in all but one case a significant injury was found. There were no false negative results. In a single patient the transverse colon was perforated during the insertion of the lavage catheter. Diagnostic, percutaneous peritoneal lavage is a simple, safe, rapidly performed, accurate technique designed to detect intraperitoneal blood and the results of this review suggest that it has a role to play in the decision-making process when assessing adult patients who have suffered blunt abdominal trauma.

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