Treatment of Hodgkin's lymphoma.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
A McMillan
Publications and source records attributed to A McMillan.
Selective inhibition of human immunodeficiency viruses by racemates and enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine.
2',3'-Dideoxy-5-fluoro-3'-thiacytidine (FTC) has been shown to be a potent and selective compound against human immunodeficiency virus type 1 in acutely infected primary human lymphocytes. FTC is also active against human immunodeficiency virus type 2, simian immunodeficiency virus, and feline immunodeficiency virus in various cell culture systems, including human monocytes. The antiviral activity can be prevented by 2'-deoxycytidine, but not by other natural nucleosides, suggesting that FTC must be phosphorylated to be active and 2'-deoxycytidine kinase is responsible for the phosphorylation. By using chiral columns or enzymatic techniques, the two enantiomers of FTC were separated. The (-)-beta-enantiomer of FTC was about 20-fold more potent than the (+)-beta-enantiomer against human immunodeficiency virus type 1 in peripheral blood mononuclear cells and was also effective in thymidine kinase-deficient CEM cells. Racemic FTC and its enantiomers were nontoxic to human lymphocytes and other cell lines at concentrations of up to 100 microM. Studies with human bone marrow cells indicated that racemic FTC and its (-)-enantiomer had a median inhibitory concentration of > 30 microM. The (+)-enantiomer was significantly more toxic than the (-)-enantiomer to myeloid progenitor cells. The susceptibilities to FTC of pretherapy isolates in comparison with those of posttherapy 3'-azido-3'-deoxythymidine-resistant viruses in human lymphocytes were not substantially different. Similar results were obtained with well-defined 2',3'-dideoxyinosine- and nevirapine-resistant viruses. (-)-FTC-5'-triphosphate competitively inhibited human immunodeficiency virus type 1 reverse transcriptase, with an inhibition constant of 2.9 microM, when a poly(I)n.oligo(dC)19-24 template primer was used. These results suggest that further development of the (-)-Beta-enantiomer of FTC is warranted as an antiviral agent for infections caused by human immunodeficiency viruses.
Antiviral Agents↗
Activities of the four optical isomers of 2',3'-dideoxy-3'-thiacytidine (BCH-189) against human immunodeficiency virus type 1 in human lymphocytes.
Four different isomers of 2',3'-dideoxy-3'-thiacytidine [beta-DL-(+-)-BCH-189] were evaluated in primary human lymphocytes infected with human immunodeficiency virus type 1. The beta-L-(-) isomer was the most potent enantiomer, with a median effective concentration of 1.8 nM and no discernible cytotoxicity up to 100 microM. The relative order of potencies for the isomers was beta-L-(-) greater than beta-DL-(+-) racemic greater than beta-D-(+) greater than alpha-L-(+) greater than alpha-D-(-). The beta-L-(-) enantiomer was as potent as 3'-azido-3'-deoxythymidine.
Antiviral Agents↗
Myocardial dysfunction in patients infected with HIV: prevalence and risk factors.
OBJECTIVES: To determine the prevalence of and risk factors for myocardial dysfunction in HIV infection. SUBJECTS: 173 patients infected with HIV underwent echocardiography. 119 were current or previous injection drug users, 38 were homosexuals, 10 were haemophiliac patients, and six were heterosexual. MAIN OUTCOME MEASURE: Detection of impaired ventricular function. RESULTS: 26 patients with abnormalities of ventricular size or function or both were identified. The abnormality was (a) dilated cardiomyopathy in 13 patients (eight homosexuals, three drug users, and two haemophiliacs) with a mean CD4 count of 38 cells/mm3, which accords with end-stage disease (in addition, three patients were identified as having borderline impairment of left ventricular function); (b) left ventricular dilatation without loss of function in a further six patients; and (c) isolated right ventricular dilation in seven patients. Follow up echocardiograms were obtained in 71 patients, 18 of whom had myocardial dysfunction (103 echocardiograms, mean (SD) 2.5 (0.6) scans per patient, mean interval 200 (116) days, range 14-538 days). These showed that in four cases of isolated right ventricular dilatation, one of isolated left ventricular dilatation, and two with borderline left ventricular dysfunction myocardial function subsequently reverted to normal. There was no excess of exposure to zidovudine in the patients with myocardial dysfunction. Similarly, patients with myocardial dysfunction had no serological evidence of excess secondary infection with Toxoplasma gondii and cytomegalovirus. CONCLUSIONS: There was a high prevalence and wide range of myocardial dysfunction in HIV positive patients. Dilated cardiomyopathy was a feature of advanced HIV disease and affected all major risk groups for HIV infection. In contrast, isolated dilatation of either ventricle occurred at an earlier stage of HIV infection and, particularly in the case of the right ventricle, often was transient. Neither treatment with zidovudine nor infection with Toxoplasma gondii or cytomegalovirus seemed to be responsible for these findings.
Adult↗
Enzyme immunoassay for anti-treponemal IgG: screening or confirmatory test?
AIMS: To review the performance of the Venereal Diseases Research Laboratory (VDRL) test and the Treponema pallidum haemagglutination assay (TPHA) as a combined screen for syphilis to provide a baseline for assessing screening by anti-treponemal IGG EIA. METHODS: Between 1980 and 1987 all serum samples were screened by both VDRL and TPHA tests. The FTA-ABS test was also used in suspected early primary syphilis, or when one of the other tests was positive. A positive result in a screening test was confirmed by quantitative testing. From 1988 all specimens were screened with an enzyme immunoassay (Captia Syph G) as a single screening test. RESULTS: Of the 44 primary, 47 secondary, and 38 early latent cases of syphilis, the VDRL and TPHA detected 32 (73%) and 31 (71%) of the primary cases; the combination detected 37 (84%). All 85 cases of cases of secondary and early latent infection were reactive in the TPHA test, whereas the VDRL was reactive in only 68 (80%). EIA had a reported sensitivity of 82% for primary infection. CONCLUSIONS: EIA can be used as a single screening test for detecting early syphilis because its results are comparable with those of the combined VDRL and TPHA tests. The conventional VDRL test should not be used as a single screening test.
Antibodies, Bacterial↗
A serovar analysis of heterosexual gonorrhoea in Edinburgh 1986-90.
OBJECTIVE: To analyse the frequency of different gonococcal serovars within Edinburgh, Scotland and to describe changes that occurred in the frequency of such serovars over time. METHODS: All heterosexual patients with a diagnosis of gonorrhoea confirmed on culture between January 1986 and December 1990 had their gonococcal strain serotyped. Temporal changes in the prevalence of gonorrhoea and the serovar of the isolates were analysed. RESULTS: Isolates of Neisseria gonorrhoeae from 1356 episodes of gonorrhoea were serotyped. Three serovars, Bajk (IB-3/IB-6), Bacejk (IB-1/IB-2) and Aedgkih (IA-1/IA-2), dominated, occurring in two-thirds of all infections. Over the study period Bajk (IB-3/IB-6) and Aedgkih (IA-1/IA-2) isolates declined in frequency in parallel with an overall fall in the prevalence of gonorrhoea but Bacejk (IB-1/IB-2) persisted at a lower but fairly constant level. Despite a fall in the number of gonococcal infections the variety of new serovars being isolated fluctuated. CONCLUSIONS: The ability of some serovars to persist while others decline in incidence may be partially related to antibiotic sensitivities but other factors such as an ability to evade the immune response and transfer of serovars from one population group to another may also be important.
Antigens, Bacterial↗
Cold sores and safer sex.
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Acute Disease↗
Rectal gonorrhoea and unsafe sex.
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Gonorrhea↗
What is the value of autologous bone marrow transplantation in the treatment of relapsed or resistant Hodgkin's disease?
The treatment of Hodgkin's disease after relapse from chemotherapy or when resistant to chemotherapy rarely results in cure. For this reason high dose therapy and autologous bone marrow transplantation (ABMT) have been explored in an attempt to overcome drug resistance by drug escalation. The results of studies published to date are encouraging but the procedure is not without significant morbidity and mortality. The answer as to whether high dose therapy and ABMT represent an improvement over conventional salvage therapy will have to await the results of randomized trials. It remains possible that the encouraging results achieved so far have been achieved by inadvertent patient selection.
Antineoplastic Combined Chemotherapy Protocols↗
Changing trends of gonococcal infection in homosexual men in Edinburgh.
In an attempt to explain the recent resurgence of homosexually-acquired gonorrhoea in the Lothian region of Scotland the number of infections and pattern of infection (urethral, rectal and pharyngeal) of all gonococcal isolates from homosexual men attending the Department of Genitourinary Medicine at Edinburgh Royal Infirmary between 1985 and 1990 were analysed. Serovar typing data were available from infections acquired between January 1986 and December 1990. A correlation between one serovar, Bacejk/Brpyust, and the overall pattern of gonorrhoea was observed. The number of infections caused by minor serovars also correlated with rates of gonococcal infection. The number of minor serovars isolated, which may represent strains from other geographical locations, is related to the total incidence of gonorrhoea. It is possible that the incidence of Bacejk/Brpyust may be determined by the size of the infected pool of gonorrhoea. The most likely explanation for the recent increase in gonorrhoea is a change in sexual behaviour and/or an influx of strains from other geographical areas.
Adult↗
Patterns of homosexually acquired gonococcal serovars in Edinburgh 1986-90.
AIM: The aim of this study was to observe the changes in gonococcal serovar pattern in homosexual men over a 5 year period. METHODS: All men who presented to the Genitourinary Medicine clinic at Edinburgh Royal Infirmary between 1986 and 1990 with homosexually acquired gonococcal infection were included in the study. Gonococcal isolates were serotyped and the temporal change in isolated serovars noted. RESULTS: Over the 5 year period 32 different serovars were associated with 175 homosexually acquired infections. There was a dynamic temporal change in the dominant serovars with a continual influx of new strains some of which become established in the community but most of which appeared only transiently. Rapid variation in incidence over time was observed for certain serovars while others remained at more constant levels. There was a marked association between certain serovars (Ae/Av; Back/Bropyt; Bacejk/Brpyut; Bacejk/Brpyust; Baejk/Brpyut) and homosexually acquired infection. CONCLUSIONS: Possible determinants for the patterns observed are discussed but the underlying mechanism is probably multifactorial.
Gonorrhea↗
An analysis of false positive reactions occurring with the Captia Syph G EIA.
AIM: The Captia Syph G enzyme immuno assay (EAI) offers the potential for the rapid automated detection of syphilis antibodies. This study was designed to assess the role of other sexually transmitted diseases (STDs) in producing false positive reactions in the Captia Syph G EIA. The role of rheumatoid factor (RF) as a potential source of false positives was also analysed. METHODS: Patients who attended a genitourinary medicine (GUM) department and gave a false positive reaction with the EIA between 1988 and 1990 were compared with women undergoing antenatal testing and with the control clinic population (EIA negative) over the same time period. The incidence of sexually transmitted disease (STD) in the clinic population and the false positive reactors was measured in relation to gonorrhoea, chlamydia, genital warts, candidiasis, "other conditions not requiring treatment" and "other conditions requiring treatment." Male: female sex ratios were also compared. Ninety two RF positive sera were analysed with the EIA. RESULTS: The rate of false positive reactions did not differ with respect to the diagnosis within the GUM clinic population. The antenatal group of women, however, had a lower incidence of false positive reactions than the GUM clinic group. No RF positive sera were positive on Captia Syph G EIA testing. CONCLUSIONS: There is no cross reaction between Captia Syph G EIA and any specific STD or with RF positive sera. The lower incidence of false positive reactions in antenatal women is unexplained but may be related to physiological changes associated with pregnancy.
False Positive Reactions↗
Influence of human immunodeficiency virus infection on treponemal serology, in patients who have been treated for syphilis.
Sera from 20 homosexual men who were infected with the human immunodeficiency virus (HIV) and had been treated previously for syphilis, were examined for cardiolipin and treponemal antibodies by the Venereal Diseases Research Laboratory (VDRL) test, and the Treponema pallidum haemagglutination assay (TPHA) and fluorescent treponemal antibody absorbed test. In only one case was probable reactivation of syphilis, as judged by rising titres in the VDRL test, noted.
Adult↗
An immunohistological study of condylomata acuminata.
Using an indirect immunoperoxidase method and a panel of monoclonal antibodies, anogenital warts removed from 86 individuals (28 heterosexual men, 47 homosexual men and 11 women) were studied. A constant feature was the presence of a stromal infiltrate of lymphocytes, in which CD4+ and CD8+ cells appeared in a ratio of about 5:1. Cells expressing interleukin-2 receptors were found in the stroma, amounting to 10% of the CD3+ cells. Leu 6+ epidermal dendritic cells (Langerhans' cells) were present in each wart; their density and morphology were similar to that in adjacent, apparently normal, skin. The mean number of Langerhans' cells that expressed HLA-DQ was lower than that of HLA-DR + cells. In 40 warts, HLA-DR was expressed on the surface of keratinocytes. Leu 7+ and Leu 11b+ cells were found in the epidermis of 17 and five warts, respectively. B-cells were noted in only five warts. These results are discussed in relation to persistence of wart virus infection.
Adolescent↗
An immunohistological study of spontaneous regression of condylomata acuminata.
An immunohistological study of four men whose perianal warts were undergoing spontaneous regression was undertaken, and the results compared with those obtained from non-regressing condylomata from six men. CD4+ and CD8+ cells were noted in the stroma of each wart, but there was no clear difference in the density of the infiltrate between regressing and non-regressing warts. Natural killer cells (CD16+ and CD57+) were only noted in the stroma and epidermis of regressing warts. Possible immunological mechanisms of regression of condylomata acuminata are discussed.
Anus Neoplasms↗
Sexual assault of men: a series.
The case records of five male victims of sexual assault presenting to two genito-urinary clinics are presented. The cases were chosen to illustrate the variety of presentations and possible sequelae of sexual assault of adult males.
Adolescent↗
Immunological study of condylomata acuminata in men infected with the human immunodeficiency virus.
As condylomata acuminata often persist in individuals infected with the human immunodeficiency virus (HIV), an immunohistological study of warts from infected men was undertaken to further knowledge about human papillomavirus persistence in this group. Using an indirect immunoperoxidase method and a panel of monoclonal antibodies, the phenotypes of cells were studied in cryostat sections of perianal or anal warts removed from 14 HIV-infected men (10 homosexual and 4 heterosexual) and from 16 non-infected men (10 homosexual and 6 heterosexual). Although the median numbers of CD1+, CD3+ and CD4+ cells per unit area were similar in each group of individuals, the number of CD8+ cells was significantly higher in HIV-infected homosexual men when compared with non-infected individuals and HIV-infected heterosexual men. The median CD4+ cell count in the peripheral blood was significantly higher in HIV-infected heterosexual men than in HIV-infected homosexual men (P less than 0.05). These findings may reflect differences in duration of HIV infection between the two groups. There was no significant difference in the proportion of cells expressing interleukin-2 receptors between HIV-infected and non-infected individuals. Natural killer (CD16+) cells were not identified in any of the condylomata.
Adult↗
Management of intrameatal warts in men.
The case notes of 1080 men with genital warts were analysed retrospectively over a 30-month period. One hundred and forty patients were identified with intrameatal warts and an audit of their treatment is discussed. When electrocautery and cryotherapy were compared the former produced a more rapid resolution of the lesions. Cystourethroscopy was performed on 16 patients with intrameatal warts. No patient had involvement beyond the distal 3 cm of the urethra. Data on concurrent sexually transmitted diseases, population characteristics and pattern of referral are presented and compared to previously reported studies.
Adolescent↗