Biomedical subjects
Publications and source records attributed to D A Cooper.
A case of nasopharyngeal cyst in a 30-year-old male homosexual intravenous drug user infected with the human immunodeficiency virus (HIV) is presented. The similarity in clinical presentation of nasopharyngeal cyst and Kaposi's sarcoma is discussed.
A possible cofactor in human immunodeficiency virus (HIV) infection is the Epstein-Barr virus (EBV), which is divided into two primary types that differ significantly in their transformation efficiency. The B-type EBV cell line is much more difficult to establish than the A-type. The extent of systemic B-type EBV infection was assessed in HIV-positive subjects and controls. Lymphoblastoid cell lines were established from 26 HIV-positive subjects and analyzed for the presence of A- or B-type EBV by Southern analysis and immunoblotting. Some 19% of HIV-positive persons were infected with B-type EBV, 69% with A-type, and 12% with both types. Analysis of the individual strains of EBV harbored by the HIV-positive subjects showed that HIV-induced immunosuppression had not led to increased susceptibility to repeated EBV infections. However, the occurrence of B-type infection in HIV-positive subjects was sixfold higher than that in the general community, indicating that HIV-induced immunodeficiency or HIV itself specifically enhanced the expression of the B-type EBV.
In a multicentre study of zidovudine therapy in Australia commencing in June 1987, 308 homosexual or bisexual men with AIDS started on zidovudine by 30 June 1988. Using follow-up data collected through 31 December 1988, the outcome of the first 18 months of zidovudine therapy in these patients has been analysed in terms of efficacy, expressed as survival and as time to development of a new AIDS-defining condition, and in terms of safety, expressed as toxicity. Median survival from time of diagnosis of AIDS was 124 weeks, significantly longer (P less than 0.001, logrank statistic) than the median survival of 44 weeks in historical controls representing AIDS patients prior to the availability of zidovudine therapy. Median survival time from starting zidovudine has not been reached in these patients, while 172 (56%) developed new AIDS-defining conditions, with median time to progression of 48 weeks. Anaemia requiring transfusion was experienced by 155 patients (50%). Significant differences (P less than 0.01, logrank statistic) in survival were found in favour of patients who commenced zidovudine therapy (Dx-zidovudine time) within 12 weeks of diagnosis and had baseline Karnofsky scores greater than or equal to 80, haemoglobin greater than or equal to 11 g/dl, CD4+ cell counts greater than or equal to 50 x 10(6)/l. Therapy-related significant differences (P less than 0.01, logrank statistic) in survival were found in favour of patients with no weight loss and who received the full zidovudine dose (1.2g) during the first 52 weeks of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Non-Hodgkin lymphoma (NHL) in a human immunodeficiency virus (HIV)-infected person is an AIDS-defining condition. There is both an increased incidence of NHL and a poorer prognosis for the disease in these HIV-infected persons, compared with patients who spontaneously develop NHL. A series of 41 consecutive patients with HIV-associated NHL treated at St Vincent's Hospital, Sydney, between 1984 and September 1989 was assessed. Of these, 36 had NHL proven on biopsy and NHL was diagnosed clinically in the other five. On histologic examination 11 had high-grade malignant lymphoma, small non-cleaved cell (SNCC) type, similar to Burkitt lymphoma, 18 had high-grade lymphoma large cell immunoblastic (LCI) type, and seven could not be classified due to inadequate material for assessment. The clinical features of these two groups were compared. Those patients with LCI had advanced CD4+ immunodeficiency and poor survival (median = 6 weeks). The other group with SNCC had better preserved immune function, and longer survival (median = 18 weeks). Three patients had survived longer than 3 years all of whom had SNCC lymphoma as their first AIDS-defining illness. The clinical features and prognostic factors demonstrated in this study document heterogeneity of NHL in HIV-infected patients and should be used as a guide to treatment of these patients, by reserving more intensive treatment for those persons with better prognostic features.
Gastrointestinal disease in AIDS is common and is due to opportunistic infections, aggressive malignancy and possible direct HIV enteropathy. Disabling gastrointestinal symptoms are prominent both in patients with established AIDS and in patients with earlier stages of HIV infection. We report the cases of 160 patients with AIDS who underwent gastroenterological investigations at St Vincent's Hospital, Sydney, between November 1983 to October 1987. Of these, 127 had the diagnosis of AIDS established prior to referral and 33 patients had the diagnosis of AIDS established as a result of gastroenterological investigations. Diarrhoea and weight loss (88%) were the most frequent reasons for undertaking gastroenterological investigations. Swallowing disorders (47%), abdominal pain (20%), oral and perianal disease (74%) and evidence of hepatobiliary disease were the other major indications for investigation. In 90% of cases there was evidence of concurrent and active gastrointestinal disease at two or more sites within the alimentary tract. Results from this series reveal a wide range of infectious pathogens: viral (Cytomegalovirus, Herpes simplex), bacterial (Mycobacterium avium intracellulare) and parasitic (Cryptosporidium, Isospora belli). Kaposi's sarcoma and non-Hodgkin's lymphoma were the only malignancies detected in this series. Gastrointestinal disease associated with HIV infection is common, and contributes significantly to its overall morbidity and mortality. Moreover, chronic diarrhoea, weight loss and malnutrition may also contribute to the overall immunodeficiency.
A group of 34 homosexual men with acquired immune deficiency syndrome (AIDS) spectrum disorders were assessed for cognitive impairment on a range of neuropsychological tests. There were 17 patients with AIDS, and 17 with AIDS-related complex (ARC). Although none of the patients showed signs of the severe dementing syndrome that has been described in persons with HIV infection, they demonstrated signs of cognitive impairment consistent with organic brain dysfunction. The profile of deficits shown by AIDS and ARC patients could be broadly grouped into disorders of recent and delayed memory and learning, generalized cognitive slowing, and reduced mental flexibility. Considerations of the clinical and neuropathological similarities between subcortical dementing syndromes and HIV-related cognitive impairment suggest that in both processes the pathogenesis of the observed deficits may involve disruption of frontodiencephalic projections.
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Between January 1, and October 31, 1987, 420 homosexual men who participated in a cohort study of infection with the human immunodeficiency virus (HIV) completed a questionnaire that examined their sexual practices during the previous six months. Of the subjects, 205 (48.8%) men were HIV-seropositive and 215 (51.2%) men were HIV-seronegative. Although there was an appreciable level of condom usage in both groups, 13.5% of the HIV-seronegative men had engaged in unprotected receptive anal intercourse and 6.3% of the HIV-seropositive men had engaged in unprotected insertive anal intercourse. Condom breakage was reported on approximately 6% of occasions by a minority of subjects. Among subjects who were in a relationship with a regular male sexual partner, the most commonly reported sexual practices were deep kissing, mutual masturbation and receptive oral intercourse without ejaculation. No HIV-seronegative man engaged in unprotected receptive and/or insertive anal intercourse, receptive oral intercourse with ejaculation or receptive and/or insertive "fisting" with a regular partner who was HIV-seropositive. No HIV-seropositive man engaged in unprotected insertive anal intercourse to ejaculation with an HIV-seronegative partner, although they did so with partners who were HIV-seropositive or of unknown status. On multivariate analyses the subject's antibody status was found to be associated with receptive anal intercourse with a condom (P = 0.007) and mutual masturbation (P = 0.001), with HIV-seronegative men being more likely to practise either; no significant independent effect was associated with the partner's antibody status. These findings provide important information on the types and levels of sexual practices in a group of homosexual men after the recognition of the acquired immunodeficiency syndrome in this country.
By means of prospective cohort data from the Sydney AIDS Project, we report on 55 homosexual or bisexual men who have become infected with human immunodeficiency virus (HIV), as measured by the development of serum HIV antibodies (seroconversion). We have compared the sexual practices, recreational drug abuse, history of sexually-transmissible diseases, and antecedent immunological findings of the men who seroconverted with those of 588 subjects who persistently remained seronegative in the same time-period. The cumulative incidence rate of HIV infection over the three years of observation was 8.5%. The cumulative incidence rate ranged from less than 1% for the six months before August 1, 1984, to a peak of 5% in the six months before August 1, 1985. Of those subjects for whom we had data for the period of seroconversion, all but two of the subjects who seroconverted admitted to a recognized high-risk sexual practice in the six months before the first visit at which they were found to be seropositive. Univariate analysis found that men who seroconverted were significantly more likely to have had a greater number of recent sexual partners (relative risk per partner, 1.02; P less than 0.001), to have engaged in receptive anal intercourse (incidence rate ratio, 3.1; 95% confidence interval [CI], 1.3-7.6; P = 0.01) and to have used nitrite inhalant (incidence rate ratio, 2.6; 95% CI, 1.2-5.9; P = 0.02) and amphetamine (incidence rate ratio, 4.8; 95% CI, 2.2-10.5; P less than 0.001) drugs. The men who seroconverted were significantly (incidence rate ratio, 2.7; 95% CI, 1.2-6.1; P = 0.014) more likely to have antecedent T-suppressor-cell counts of greater than 800 cells/microL. Factors that retained significance in multivariate analysis were the number of recent sexual partners, recent amphetamine abuse and a T-suppressor-cell count of greater than 800 cells/microL.
cDNA clones for chicken adipose lipoprotein lipase were isolated from an expression library in lambda gt11 by antibody screening and characterized by hybridization selection and nucleotide sequencing. Based on the cDNA sequence and on N-terminal sequence analysis of the purified enzyme, chicken adipose lipoprotein lipase is a mature protein of 465 amino acids with a signal peptide of 19 or 25 amino acids, depending on which of two methionine residues is used for translation initiation. The predicted amino-acid sequence was found to be 73-77% identical to the four known mammalian adipose lipoprotein lipase sequences, with conservation of position of cysteine residues and putative functional domains, and number of potential N-glycosylation sites. Chicken lipoprotein lipase differs from mammalian lipoprotein lipases with respect to the position of one N-glycosylation site and the presence of an additional 15-17 C-terminal amino acids. 32P-labeled cDNA clones hybridized to mRNA species of 3.7 and 4.0 kb in Northern blots of heart and adipose, but not of liver RNA. In chickens that were fasted for 48 h and then refed, lipoprotein lipase mRNA levels in adipose increased to a maximal level of 350% that of controls at 10 h, whereas heart lipoprotein lipase mRNA levels fell to 40% of controls at 14 h. Concomitantly, no changes in total RNA were observed. Thus, avian lipoprotein lipase is subject to reciprocal pretranslational regulation in adipose and heart.
The duration of survival of all persons with the acquired immunodeficiency syndrome (AIDS) in Australia who were diagnosed to July 31, 1987 was analysed by means of standard Kaplan-Meier methods in order to construct survival curves, and by log-rank tests which were used to assess the significance of differences among the curves. The median duration of survival was 10.4 months. Significant (P less than 0.001) differences in the survival curves were found between men and women (median survival, 11.4 and 3.8 months, respectively) by the log-rank test. Patients who were aged 20-49 years at diagnosis had a longer (P less than 0.001) median survival (11.4 months) than did those who were older than 60 years of age (2.7 months) and those who were aged less than 20 years (0.5 months) at diagnosis. Those patients who were infected by way of blood transfusions had a shorter (P less than 0.001) median survival (1.6 months) than did those who were infected through homosexual activity (11.4 months). Median survival time, which was stratified by the disease stage at presentation, varied from 12.4 months in those patients with Kaposi's sarcoma alone to 7.0 months in those patients with lymphoma (P = 0.01). The median survival time for those patients who presented solely with Kaposi's sarcoma was shorter than was that which has been reported from other developed countries. Multivariate analysis of all male cases by means of the proportional-hazards model indicated that the presentation of cases at an age that was greater than 50 years (relative risk, 2.36; 95% confidence interval [CI], 1.63-3.42) was associated independently with a reduced survival time, while the presentation of cases solely with Kaposi's sarcoma (relative risk, 0.67; 95% Cl, 0.49-0.92) was associated independently with an increased survival time. When all cases were included in this analysis, these same predictors of survival were significant; in addition, cases of AIDS as a result of the receipt of a blood transfusion were associated independently with a reduced survival time.
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The performance of 56 homosexual men infected with human immunodeficiency virus (HIV) was compared to that of 23 HIV antibody-seronegative controls on simple (SRT) and choice (CRT) reaction time tasks. Patients were classified into 3 groups according to Centers for Disease Control clinical criteria. There were 18 patients who had acquired immunodeficiency syndrome (AIDS), 18 who had AIDS-related complex (ARC), and 20 who were HIV antibody-seropositive but otherwise asymptomatic (HIV-Ab+). The SRT task consisted of 5 trials, each containing 10 target stimuli. The CRT task consisted of 10 trials, each containing 5 target stimuli randomly interspersed with 5 nontarget stimuli. The mean response latency of each of the patient groups on the SRT task was not significantly different from that of controls. However, the performance of patients with AIDS or ARC on the CRT task was significantly lower than that of controls, whereas that of HIV-Ab+ patients was not. Analysis of the quality of RT task performance also indicated that the impairment of processing efficiency at higher levels of task difficulty reflected a disruption of processing prior to the response selection stage.
A high proportion of HIV-positive sera were found to react with 130- and 180-kDa antigens which were present in the Jijoye cell line. The majority of the HIV-positive sera which detected these antigens also contained antibodies to Epstein-Barr virus (EBV) nuclear antigen 2B (EBNA2B) suggesting a relationship between B-type EBV strains and the expression of the 130K/180K antigens. Cell lines were established by infection of B lymphocytes with different A- and B-type strains of EBV. Incubation of these lines with sera from individuals infected with either A-type or B-type EBV strains demonstrated that the 130K and 180K antigens were only expressed by cell lines containing B-type virus. Sera from individuals infected with A-type EBV did not react with the 180K antigen in any cell lines but could detect EBNAs 3, 4, and 6 antigens in the A-type cell lines. Restriction enzyme analysis of the BamHI E region of the EBV genome revealed marked differences between the A and B types of the virus. These results demonstrate that expression of antigens encoded from the BamHI E region of EBV (EBNAs 3, 4, and 6) are altered in cell lines transformed by B-type strains of EBV.
This report concerns three patients with human immunodeficiency virus (HIV) infection in whom malignant melanoma developed. One patient had metastatic malignant melanoma, one had iris melanoma, and one had a single skin melanoma. All three had lower absolute numbers of CD4+ cells than a control group, and the severity of their disease was inversely proportional to the absolute number of CD4+ cells. This report suggests an association between the immunodeficiency resulting from HIV infection and the development of malignant melanoma.
Three cases of oesophageal candidiasis in association with primary HIV infection are described. In each case the candidiasis was associated with a decreased number of circulating CD4+ cells and responded well to treatment with ketoconazole. Clinicians should be aware that severe opportunistic infections may develop during this stage of infection, presumably as a result of transient immunodeficiency. We argue that the definition of primary HIV infection should be extended to include severe opportunistic infections and neurologic presentations.
Neurological manifestations of unknown cause occurring in patients who become or are HIV antibody positive with presumed normal immune function have been described recently. This report adds a further six cases, all of whom had normal CD4+ cell counts either throughout the period of observation or after the episode of seroconversion. Three had an acute presentation, two in the context of documented seroconversion consisting of one of the following: an encephalitis, an ataxia, and confusion with neuralgic amyotrophy. Three had a subacute disorder occurring at a later phase of HIV infection but before opportunistic infections or neoplasms, and marked by a static mild cognitive deficit. This report extends the range of abnormalities that may be seen at seroconversion and documents the presence of a non-progressive cognitive deficit occurring in the latent phase of HIV infection.
In 1982, one year after the first cases of the acquired immunodeficiency syndrome (AIDS) were reported, a case definition of AIDS was produced by the Centers for Disease Control, Atlanta, Georgia, USA. This definition was implemented world-wide, and it allowed the standardization of the reporting of cases. The identification of the virus that is responsible for AIDS, which subsequently was named the human immunodeficiency virus type 1 (HIV-1), led to the development of laboratory test procedures to detect its presence. The use of these tests confirmed that additional clinical manifestations were associated with severe outcomes of HIV-1 infection, which resulted in an increase in the number of conditions that were encompassed by AIDS. Moreover, the diagnosis of many AIDS-defining conditions could be made presumptively in the presence of proved HIV-1 infection. Thus the case definition required revision in 1985, and again in 1987. In addition, clinical expressions other than AIDS definitively were attributed to infection with HIV-1 after the widespread use of the testing procedures. The case definition of AIDS, as revised by the Centers for Disease Control in 1987, now is the current definition that is used in Australia. The clinical classification of HIV infection, which was produced by the Centers for Disease Control in 1986, was implemented in this country in January 1988.