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J Downie

Publications and source records attributed to J Downie.

At least 19 recordsLinked to original sources
PubMed2000

Direct visualization of HIV-1-specific cytotoxic T lymphocytes during primary infection.

OBJECTIVE: HIV-specific cytotoxic T lymphocytes (CTL) are believed to play an important role in containing viral replication throughout HIV-1 infection. Previous studies have attempted to quantify the HIV-1-specific CTL precursor frequency during primary HIV infection by using limiting dilution analysis, which almost certainly underestimates the true CTL frequency. Here we use a relatively new technique to quantify HIV-specific CD8 T cells in primary HIV infection. METHODS: We have used soluble tetrameric complexes of HLA class I molecules complexed with HIV epitope peptides to study the dynamics and frequency of HIV-specific CD8 T cells in relation to plasma viral load in early HIV infection, in three patients with a highly focused HIV-specific CTL response. RESULTS: We show that the frequencies of HIV-1-specific CD8 T cells in acute infection are significantly higher than previously documented and can be demonstrated well before full seroconversion. These studies also confirm the immunodominance of the B27-restricted response in HIV infection and demonstrate a close temporal relationship between the numbers of circulating HIV-specific CD8 T cells and viral load. CONCLUSIONS: These findings strongly suggest that HIV-1-specific CD8 T cells are responding directly to the level of viral replication in early HIV infection and are a major factor in its control. In addition, the data indicate that immunodominance for CD8 T-cell responses is established in the acute phase of HIV infection.

Adult↗
PubMed2000

High frequency of cytomegalovirus-specific cytotoxic T-effector cells in HLA-A*0201-positive subjects during multiple viral coinfections.

How the cellular immune response copes with diverse antigenic competition is poorly understood. Responses of virus-specific cytotoxic T lymphocytes (CTL) were examined longitudinally in an individual coinfected with human immunodeficiency virus type 1 (HIV-1), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). CTL responses to all 3 viruses were quantified by limiting dilution analysis and staining with HLA-A*0201 tetrameric complexes folded with HIV-1, EBV, and CMV peptides. A predominance of CMV-pp65-specific CTL was found, with a much lower frequency of CTL to HIV-1 Gag and Pol and to EBV-BMLF1 and LMP2. The high frequency of CMV-specific CTL, compared with HIV-1- and EBV-specific CTL, was confirmed in an additional 16 HLA-A*0201-positive virus-coinfected subjects. Therefore, the human immune system can mount CTL responses to multiple viral antigens simultaneously, albeit with different strengths.

Adult↗
PubMed1998

Aetiology of childhood proptosis.

OBJECTIVE: To retrospectively analyse causes of childhood proptosis and their investigations and treatment. METHODOLOGY: The records of children under 15 years of age presenting with proptosis to The Children's Hospital, Camperdown, Sydney, were reviewed for the period 1983-93 inclusive. RESULTS: Fifty-seven cases of proptosis were found. In order of frequency the causes were; orbital cellulitis 22, thyroid eye disease 8, optic nerve +/- optic chiasm glioma 8, orbital rhabdomyosarcoma 7, metastatic neuroblastoma 4, orbital neurofibroma 3, orbital haemangioma 2, metastatic Ewing's sarcoma 2 and orbital dermoid cyst 1. Treatment depended on the cause (antibiotics, antithyroid drugs, chemotherapy, radiotherapy, surgery) and was multidisciplinary. CONCLUSIONS: The most common cause of proptosis in children presenting to The Children's Hospital, Camperdown, Sydney, was infective orbital cellulitis. The most useful initial investigation was an orbital computed tomography scan. Treatment depended on the cause of the proptosis and was multidisciplinary.

Adolescent↗
PubMed1994

Assessment of self-report in HIV surveillance: a pilot study.

The basis of HIV exposure category classification was investigated among selected cases of newly diagnosed HIV infection. Questionnaires seeking specific information on patient-reported exposure to HIV were forwarded to doctors who had requested the HIV antibody test for patients who met the study sample criteria. The cases of interest were those newly diagnosed between 1 January and 31 October 1991 and notified to state and territory health authorities as having been attributed to exposures to HIV other than male homosexual contact or receipt of blood, blood products or tissue. A total of 158 questionnaires was forwarded and 59 per cent were returned. Among the returned questionnaires included in the study sample, exposure to HIV on the original notification to the health authority was given as injecting drug use (8 per cent, 3 of 37), heterosexual contact (46 per cent, 17 of 37), or unavailable (46 per cent, 17 of 37). A clear basis for HIV exposure category classification was provided on the questionnaires for 70 per cent (7 of 10) of cases among women, whereas among men whose infection was attributed to heterosexual contact, a basis for exposure category classification was specified for only 43 per cent (10 of 23) of cases. Although the study was limited by the low response rate, use of the questionnaire provided a relatively simple means for assessing self-reported HIV exposure history.

Adolescent↗
PubMed1991

Ethics education for Canadian medical students.

This study was designed to determine the nature, extent, and quality of medical ethics education for students in Canadian medical schools. In 1989, a questionnaire that used primarily open-ended questions was sent to all 16 Canadian medical schools; they all responded. Significant findings include the following: 15 of the 16 schools provided some ethics education (with wide-ranging objectives); the amounts of time alloted for such instruction ranged from ten and a half hours to 45 hours (per degree, not per year), with no discernible pattern in the distribution of hours across the years; most teaching was case-based and issue-oriented; most instructors were physicians; and almost all the schools conducted assessments of students using a pass-fail standard.

Canada↗
PubMed1990

Prophylaxis against postsplenectomy pneumococcal infection.

An excess risk of overwhelming sepsis following splenectomy is well established. In view of this, surgical responsibility must embrace the administration of pneumococcal prophylaxis. Current recommendations vary, but routine pneumococcal vaccination, together with penicillin prophylaxis in selected patients, is advocated widely. This retrospective review of 75 patients undergoing splenectomy was undertaken in order to evaluate the extent to which current practice complies with these recommendations. Among surviving patients, the incidence of vaccination with polyvalent pneumococcal vaccine (PPV) was found to vary according to operative indication. All haematological patients received pre-operative PPV. Two-thirds of multitrauma patients were vaccinated, while 42% of patients who required splenectomy following accidental intra-operative trauma received PPV. Only 11% of patients who underwent incidental splenectomy were vaccinated. Long-term antibiotic prophylaxis was commenced in 33% of surviving patients under 20 years of age, and in 8% with underlying malignancy. These results highlight a need for greater vigilance in the administration of pneumococcal prophylaxis, particularly following accidental or incidental splenectomy.

Adult↗