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Biomedical subjects

D A Cooper

Publications and source records attributed to D A Cooper.

At least 181 records · Page 10Linked to original sources
PubMed1994

Effects of high-dose oral acyclovir on herpesvirus disease and survival in patients with advanced HIV disease: a double-blind, placebo-controlled study. European-Australian Acyclovir Study Group.

OBJECTIVE: To determine the efficacy of high-dose oral acyclovir in preventing cytomegalovirus (CMV) and other herpesvirus disease in patients with advanced HIV disease and to evaluate its effect on patient survival. DESIGN: Double-blind, placebo-controlled randomized trial of up to 1 year's therapy. SETTING: Outpatient clinics in 16 hospitals in Europe and Australia. PARTICIPANTS: A total of 302 patients with Centers for Disease Control and Prevention stage IV HIV disease, seropositive for CMV and with CD4+ lymphocyte counts < or = 150 x 10(6)/l. INTERVENTIONS: Oral acyclovir (800 mg, four times daily) or matching placebo for 48 weeks. MAIN OUTCOME MEASURES: Time to development of CMV and other herpesvirus disease. Following the results of another study, the protocol was amended to make survival a second major endpoint. RESULTS: Acyclovir failed to reduce the incidence of CMV disease: the probability of developing CMV disease at 1 year was 0.24 and 0.23 in the placebo and acyclovir groups, respectively (P = 0.53). However, acyclovir significantly reduced the probability of dying at 1 year of follow-up (from 0.39 to 0.23; P = 0.018). As expected, acyclovir significantly reduced the incidence and frequency of herpes simplex virus disease. There were no notable differences between treatment groups in clinically adverse experiences and no changes in haematological parameters to indicate clinically significant drug-induced toxicity. CONCLUSIONS: High-dose acyclovir failed to reduce the incidence of CMV disease, but significantly reduced the probability of dying at 1 year of follow-up.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Immunohistological assessment of cutaneous drug hypersensitivity in patients with HIV infection.

The pathogenesis of drug hypersensitivity in patients with HIV infection is unknown. To study further the nature of hypersensitivity, the histopathological features of morbilliform drug hypersensitivity reactions were examined in a group of HIV-infected patients. Skin sections from 23 HIV-infected subjects with morbilliform drug hypersensitivity reactions were examined by light microscopy, direct immunofluorescence and immunohistochemistry, to determine the nature of the inflammatory infiltrate and the role of immunoglobulin, complement and cytokines. The principal light microscopic findings were spongiosis, hydropic generation of the basal layer, civatte bodies, an epidermal lymphocytic infiltrate (48%), and a perivascular dermal infiltrate of lymphocytes (87%) and macrophages (52%). Two patients had findings consistent with toxic epidermal necrolysis. Immunohistochemistry demonstrated that the lymphocytic infiltrate consisted of CD8+, HLA-DR+ T lymphocytes (some of which also stained for CD38), a marked depletion of epidermal Langerhans cells (90%), and strong cytoplasmic staining of keratinocytes for IL-6 (60%), IL-1 beta (50%), tumour necrosis factor-alpha (TNF-alpha) (45%) and to a lesser degree, interferon-gamma (IFN-gamma) (35%). Immunofluorescence did not demonstrate any significant deposition of immunoglobulin or complement. The histological findings were independent of the responsible drug, the duration of either therapy or the rash, and of peripheral blood CD4+ and CD8+ cell counts. These findings suggest that activated CD8+ lymphocytes and perhaps epidermal production of cytokines are involved in the pathogenesis of cutaneous drug hypersensitivity in HIV-infected patients. The common histological features, regardless of the causative drug, suggest a common pathogenesis.

Adult↗
PubMed1994

HIV therapy advances. Early antiretroviral therapy.

AIM: To review evidence suggesting that antiretroviral therapy should be initiated at an early stage in HIV infection. METHOD: Review of published data. CONCLUSIONS: There are arguments both for and against early antiretroviral therapy. Although the reasons against are undoubtedly valid, evidence of greater efficacy, less toxicity and a delay in the development of resistance outweigh the possible disadvantages. Moreover, for some patients, early therapy may provide a chance of future benefits from more useful but currently untried treatments.

Antiviral Agents↗
PubMed1993

Zidovudine in persons with asymptomatic HIV infection and CD4+ cell counts greater than 400 per cubic millimeter. The European-Australian Collaborative Group.

BACKGROUND: Zidovudine therapy is of benefit in the treatment of symptomatic and asymptomatic human immunodeficiency virus (HIV) infection in persons with CD4+ cell counts of less than 500 per cubic millimeter. The efficacy, safety, and duration of benefit of zidovudine in those with 500 or more CD4+ cells per cubic millimeter are uncertain. METHODS: In a double-blind, placebo-controlled trial, 993 patients with asymptomatic HIV infection and CD4+ cell counts above 400 per cubic millimeter were randomly assigned to receive zidovudine (500 mg twice daily) or placebo for three years. The primary end point was progression of disease, as defined by the development of Centers for Disease Control and Prevention (CDC) group IV disease (including recurrent oral candidiasis, hairy leukoplakia, or progressive diarrhea) or two CD4+ cell counts below 350 per cubic millimeter. This outcome measure was changed from the original end point of the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex to reflect changes in recommendations for management. The study was terminated after the first interim analysis. RESULTS: Disease progression was significantly less frequent in the zidovudine group (relative risk, 0.56; 95 percent confidence interval, 0.43 to 0.75; P < 0.001 by the log-rank test). The probability of disease progression at two years was 0.19 with zidovudine, as compared with 0.34 with placebo (95 percent confidence interval for the difference, -0.21 to -0.08). Progression to CDC group IV disease was reduced by half in the zidovudine recipients (relative risk, 0.49; P = 0.049) and decline in CD4+ cell counts to below 350 per cubic millimeter was reduced by 40 percent (relative risk, 0.60; P < 0.001). The inclusion of early HIV disease events (oral candidiasis, oral hairy leukoplakia, and herpes zoster) as end points confirmed the effects of zidovudine on the progression of clinical disease (relative risk, 0.55; 95 percent confidence interval, 0.37 to 0.84; P = 0.004). The median duration of treatment was 94 weeks. Severe hematologic or clinical side effects were rare. CONCLUSIONS: Treatment with zidovudine benefits HIV-infected persons with CD4+ cell counts above 400 per cubic millimeter. Despite the use of doses larger than those now generally prescribed, zidovudine was well tolerated for up to three years by most of our patients.

AIDS-Related Complex↗
PubMed1993

Subtypes of Epstein-Barr virus (EBV) in Hodgkin's disease: association between B-type EBV and immunocompromise.

Epstein-Barr virus (EBV) has been associated with Hodgkin's disease (HD) in up to 50% of cases, but the subtype of EBV involved has only recently been studied. In this report, biopsy samples from 30 patients with HD were assessed for EBV sequences using both the polymerase chain reaction (PCR) and in situ hybridization (ISH). EBV sequences were localized to the malignant Reed-Sternberg cells and their mononuclear variants (Hodgkin's cells) in 9 of the 30 cases, with 7 demonstrating A-type and 2 B-type EBV sequences. Both of the patients with B-type EBV-associated HD had features to suggest pre-existing immune compromise: one was infected with human immunodeficiency virus (HIV) and had severe CD4+ T-lymphocyte depletion; the other was a debilitated elderly patient with dementia. A previous study suggested that A-type EBV alone is associated with HD and the finding of predominantly A-type EBV in the present series is in keeping with this report. The presence of B-type EBV in the HD of patients with pre-existing immunodeficiency, taken together with the recent report that B-type EBV occurs in HIV-associated non-Hodgkin's lymphoma, suggests that B-type EBV may be an important human pathogen in immunocompromised patients.

Actins↗
PubMed1993

HIV risk factors and seroprevalence in surgical patients.

OBJECTIVE: To determine the prevalence of risk factors for human immunodeficiency virus (HIV) infection, and HIV-1 seroprevalence, in surgical patients. DESIGN: Prospective study in which consenting patients completed a questionnaire on factors potentially related to a higher risk of HIV infection, and underwent an HIV-1 antibody test. PATIENTS AND SETTING: Both elective and emergency surgical admissions between July and November 1990 at St Vincent's Hospital, Sydney. RESULTS: Of 1292 patients who were approached to participate, 27 had been previously diagnosed with HIV-1 infection and, of the remaining 1265, eight (0.63%) refused to answer the questionnaire and undergo a blood test, and 12 (0.95%) refused the blood test only. HIV-1 antibody testing was completed for 1171 study subjects. Twenty-six of the 807 men who answered the questionnaire had been previously diagnosed with HIV-1 infection. Of the remaining 781 male patients, 133 (17%) reported a history of homosexual contact, injecting drug use or blood transfusion, 132 (17%) had had a prior HIV-1 antibody test and three were newly diagnosed with HIV-1 infection as a result of the survey. Of 476 women who completed the questionnaire, one had been previously diagnosed with HIV-1 infection, and of the remaining 475, 59 (12.4%) reported injecting drug use or a blood transfusion and 72 (15%) had had a prior HIV-1 antibody test. No women were newly diagnosed with HIV-1 infection. Of patients reporting specific factors, the proportion who had had a prior HIV-1 antibody test varied from 62% for men reporting homosexual contact to 34% for recipients of a blood transfusion between 1980 and 1985. CONCLUSION: Although an appreciable proportion of surgical patients admitted to St Vincent's Hospital reported factors associated with a higher risk of HIV infection, the prevalence of undiagnosed HIV-1 infection is very low, particularly among patients reporting no such factors.

AIDS Serodiagnosis↗
PubMed1993

HIV seroconversion illness.

HIV seroconversion is associated with characteristic clinical findings which reflect the first interaction of HIV with the host immune system. Recognition of the characteristic clinical illness associated with HIV seroconversion helps to establish an early diagnosis and obviates the need for further investigation or empiric therapy. It may also afford a unique opportunity to institute counselling to prevent the further spread of HIV in the community.

Adult↗
PubMed1993

Femtogram on-column detection of nicotine by isotope dilution gas chromatography/negative ion detection mass spectrometry.

A gas chromatographic method, utilizing detection by negative chemical ionization (NCI) mass spectrometry, is presented for the detection of nicotine. The method incorporates derivatization with heptafluorobutyric anhydride/pyridine to yield the ring-opened addition product, 1-[4-(3'-pyridyl)-4-heptafluorobutyryloxybutyl]-1- methylheptafluorobutanamide. The resulting heptafluorobutanamide is both relatively stable and an excellent electron scavenger. This methodology provides for the detection of nicotine at femtogram on-column levels, the measurement of nicotine over three orders of magnitude, and the minimization of contamination due to environmental nicotine.

Chromatography, Ion Exchange↗
PubMed1993

Factors contributing to the formation of experimentally-induced ovarian cysts in prepubertal gilts.

Manipulation of an ovary during the follicular phase in cycling gilts or prepubertal gilts treated with PMSG and hCG results in formation of cysts on manipulated ovaries and corpora lutea (CL) of normal appearance on nonmanipulated ovaries. In contrast, cysts did not form after manipulation in luteal phase gilts. In the present experiment, daily administration of 50 mg progesterone to prepubertal gilts treated with PMSG and hCG established luteal phase concentrations of progesterone but did not lessen the incidence of manipulated-induced cysts. Number of cysts formed was associated with the number of follicles > or = 5 mm at manipulation, which was inversely related to serum concentrations of progesterone. Number of receptors for LH/hCG in follicular tissues did not differ between manipulated and nonmanipulated ovaries but was greater in granulosa (P < .05) and theca (P < .08) from follicles with diameters > or = 7 mm compared to 5 and 6 mm. Contents of estradiol, androstenedione, testosterone, progesterone and prostaglandins E2 and F2 alpha in follicular fluid, granulosa and theca were not different between follicles > or = 5 mm destined to form cysts. Profiles of progesterone and estradiol in peripheral serum and duration of luteal phase concentrations of progesterone were not different for gilts with induced cysts and gilts with CL. In conclusion, manipulation of follicles resulted in a failure to ovulate. Subsequent formation of cysts did not result from or result in a loss of steroidogenic function or the ability to bind LH to follicular receptors. These results demonstrate that the mechanism for ovulation is independent of other follicular processes, since ovulation can be disrupted without altering follicular steriodogenesis or subsequent luteinization.

Animals↗
PubMed1993

Clinical and laboratory markers of hypersensitivity to trimethoprim-sulfamethoxazole in patients with Pneumocystis carinii pneumonia and AIDS.

A group of clinical, immunologic, and virologic variables was examined to determine if any predicted the development of hypersensitivity to trimethoprim-sulfamethoxazole (TMP-SMZ) during treatment of Pneumocystis carinii pneumonia in patients with human immunodeficiency virus (HIV) infection. Hypersensitivity occurred in 39 (27%) of 143 patients, who had significantly higher total lymphocyte and CD4+ and CD8+ cell counts and CD4:CD8 ratios than did those who did not develop hypersensitivity. Regression analysis identified having a CD4:CD8 ratio > 0.10 (95% confidence interval [CI], 1.75-3.94; P = .02) and treatment for < 14 days (95% CI, 1.57-3.75; P = .04) as independently predictive of hypersensitivity. Use of corticosteroids tended to reduce the frequency of hypersensitivity (7% vs. 30%; P = .07). T lymphocytes may be important in the pathogenesis of these hypersensitivity reactions. As the frequency of hypersensitivity declines with disease progression, T lymphocytes could be effector cells in these reactions or their sensitivity to TMP-SMZ may decline with HIV disease progression.

AIDS-Related Opportunistic Infections↗
PubMed1993

Breast-feeding during primary maternal human immunodeficiency virus infection and risk of transmission from mother to infant.

Examination of breast-fed infants of the complete cohort of Australian women whose primary human immunodeficiency virus (HIV) infection occurred postpartum allows for an estimate of risk of transmission of HIV. Ten women with no other risk factors were infected via blood transfusion postpartum. They breast-fed for up to 9 months; 2 of their infants were infected. Another woman, who shared needles for intravenous drug use, seroconverted 6-10 months post-partum. She breast-fed for 14 months. Retrovirus was visualized in the cellular and cell-free fraction of her milk by electron microscopy. Infection in her infant was confirmed at 12 months. Thus, 3 of the 11 babies at risk became infected, providing an estimate of risk of 27% for breast-feeding during primary maternal infection (95% confidence interval, 6-61%). These data establish the association of primary maternal HIV infection and breast-feeding with a high risk of transmission to infants.

Animals↗
PubMed1993

Patients infected with human immunodeficiency virus type 1 have low levels of virus in saliva even in the presence of periodontal disease.

In two consecutive studies, 80 subjects human immunodeficiency virus (HIV)-1-seropositive (21 asymptomatic, 6 persistent generalized lymphadenopathy, 13 AIDS-related complex, and 40 AIDS) were examined for oral lesions. Paired serum and saliva specimens were tested for HIV isolation, DNA, and antigen. HIV antigen was detected in sera from 31 patients, but not in saliva. HIV was isolated from blood mononuclear cells of 83% and saliva supernatants of 21%. In the second study of 25 patients, HIV was detected in plasma of 56% (titers, 1/10 to > 1/1000) but not in diluted saliva supernatants, even in those with severe periodontal disease. HIV DNA was detected using polymerase chain reaction in 2 of 7 saliva cell pellets and 4 of 5 blood samples. Hence, infectious HIV and DNA was found at very low concentrations in 21% and 28% of HIV-seropositive patients, respectively, at all stages of HIV infection.

AIDS-Related Complex↗
PubMed1993

Efficacy and safety of rechallenge with low-dose trimethoprim-sulphamethoxazole in previously hypersensitive HIV-infected patients.

OBJECTIVE: This study was undertaken to determine whether patients infected with HIV and with prior hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) can be rechallenged successfully with TMP-SMX, what factors predict successful rechallenge, and whether hypersensitivity is due to TMP or to SMX. DESIGN: A prospective, open study. SETTING: A tertiary referral hospital. PATIENT: Thirty-one HIV-infected patients with a history of non-life-threatening hypersensitivity to TMP-SMX. INTERVENTIONS: Patients received TMP (300 mg twice a week) for 2 weeks and, where no major reaction occurred, subsequently with TMP-SMX (160 and 800 mg per tablet, one tablet two times a day, twice a week). Patients who developed significant and persistent hypersensitivity ceased SMX and were subsequently challenged with TMP-dapsone (300 and 100 mg, respectively, twice a week). MAIN OUTCOME MEASURES: That rechallenge is more likely to be successful in those with advanced HIV disease. RESULTS: Five out of 31 (16%) patients developed hypersensitivity to TMP, and two ceased TMP as a result. Fifteen of the 26 (58%) patients who received subsequent TMP-SMX developed hypersensitivity, 12 of whom ceased TMP-SMX because of this reaction. Hypersensitivity to TMP-SMX was significantly less common in those with a CD4+ cell count < 20 x 10(6)/l than in those with a CD4+ cell count > 20 x 10(6)/l (31 versus 85%; P = 0.03). Hypersensitivity to TMP-dapsone occurred in two out of nine patients with hypersensitivity to TMP-SMX on rechallenge. One patient developed transient dyspnoea following a dose of SMX, but no other serious adverse drug reaction occurred. CONCLUSIONS: Rechallenge with TMP-SMX appears safe in HIV-infected patients with a history of non-life-threatening hypersensitivity and is most likely to be successful in patients with a low CD4+ lymphocyte count. The data suggest a low rate cross-hypersensitivity between SMX and dapsone, at least at the doses used.

AIDS-Related Opportunistic Infections↗
PubMed1993

The efficacy and safety of zidovudine alone or as cotherapy with acyclovir for the treatment of patients with AIDS and AIDS-related complex: a double-blind randomized trial. European-Australian Collaborative Group.

OBJECTIVE: To evaluate the efficacy and safety of zidovudine (ZDV) at a maintenance dose of 250 mg every 6 h alone or as cotherapy with acyclovir (ACV; 800 mg every 6 h) as treatment for AIDS and AIDS-related complex (ARC). DESIGN: Double-blind, randomized, placebo-controlled clinical trial of up to 1 year's therapy. SETTING: Teaching hospital ambulatory clinics in eight European countries and Australia. SUBJECTS: A total of 131 patients with AIDS and 134 with ARC were enrolled and followed from 1986 to 1988. MAIN OUTCOME MEASURES: Time to development of AIDS-defining opportunistic infections and AIDS-associated neoplasms, survival assessed at 1 year after entry, performance status, body weight, CD4+ cell counts. RESULTS: During the study period, 46 (36%) ZDV recipients and 37 (27%) cotherapy recipients developed opportunistic infections. The probability of an ARC patient progressing to AIDS (1982 Centers for Disease Control criteria) was 0.18 and 0.15 [95% confidence interval (CI) for difference, -0.17 to 0.11] for the ZDV alone and cotherapy recipients, respectively. After excluding patients who experienced an opportunistic infection during the first 4 weeks of therapy, the probability was 0.13 and 0.099 (95% CI for difference, -0.16 to 0.10) for the ZDV and cotherapy recipients, respectively. Thirty-six patients treated with single-agent therapy [28 (41%) AIDS and eight (12%) ARC patients] and 15 cotherapy recipients [13 (21%) AIDS and two (3%) ARC patients] died during the study. There was a significant difference in time to death between the cotherapy and ZDV alone groups for both AIDS (P = 0.014) and ARC (P = 0.045) patients, with cotherapy patients surviving longer. Infections related to herpesviruses, but not cytomegalovirus, were reduced in patients receiving ACV therapy. CD4+ cell counts in both arms generally increased initially and then declined. Forty-six per cent of patients in the ZDV group (59% of AIDS and 31% of ARC patients) and 52% of patients in the cotherapy group (69% of AIDS and 34% of ARC patients) experienced bone-marrow suppression. Red cell transfusions were administered to 33% of ZDV alone recipients and 34% of cotherapy recipients. CONCLUSION: These data show that the addition of high-dose ACV cotherapy to ZDV for patients with AIDS and advanced ARC results in a statistically significant improvement in survival with minimal increase in the risk of toxicity.

AIDS-Related Complex↗
PubMed1993

Augmentation of HIV-specific lymphoproliferation in HIV-infected individuals by TraT: a novel T-cell immunopotentiating agent.

OBJECTIVE: To evaluate the potential of TraT to restore HIV-specific cell-mediated immunity. DESIGN: CD4+ T cell-associated antiviral and recall antigen-specific lymphoproliferative responses are generally impaired or absent in HIV-infected individuals. METHODS: Using peripheral blood mononuclear cells (PBMC) from a group of asymptomatic and symptomatic HIV-infected individuals, we compared the immunomodulatory effects of exogenous interleukin-2 (IL-2) with the effects elicited by the bacterial integral membrane protein, TraT. RESULTS: Exogenous IL-2 enhanced lymphoproliferation induced by an immunodominant synthetic HIV gp41 analogue, gp41[8] (amino acids 593-604), in four out of 10 asymptomatics and six out of 19 symptomatics. In contrast, TraT acted synergistically with gp41[8] to augment HIV-specific proliferation with higher frequency and greater magnitude than exogenous IL-2. Moreover, this TraT-mediated enhancement of HIV-specific lymphoproliferation occurred in the majority of HIV-infected individuals, irrespective of CD4+ T-cell count in peripheral blood or disease status, and thus appears not to be major histocompatibility complex-restricted. TraT also augmented lymphoproliferation induced by well-known recall antigens and other less immunodominant HIV analogues. CONCLUSIONS: These findings suggest that TraT, in combination with HIV-derived peptides, could be used to maintain or restore cell-mediated immune functions of HIV-infected individuals, as well as cellular immune functions in individuals suffering from other immunodeficiency disorders.

Adjuvants, Immunologic↗