Canadians studying medicine abroad and their journey to secure postgraduate training in Canada or the United States.

Background: From national and international workforce perspectives, Canadians studying medicine abroad (CSAs) are a growing provider group. Some were born in Canada whereas others immigrated as children. They study medicine in various countries, often attempting both American and Canadian medical licensure pathways.

Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals.

Background: Multiple immune evasion strategies by which HCV establishes chronic infection have been proposed, including manipulation of cytokine responses. Prior infection with HIV increases the likelihood of chronic HCV infection and accelerates development of HCV-related morbidity. Therefore, we investigated in vitro cytokine responses to HCV structural and non-structural proteins in peripheral blood mononuclear cells (PBMC) from uninfected, HIV-infected, HCV-infected and HIV/HCV-coinfected individuals.

Cross-reactive cytotoxic T lymphocytes against human immunodeficiency virus type 1 protease and gamma interferon-inducible protein 30.

The gamma interferon (IFN-gamma)-inducible protein 30 (IP-30) signal peptide -11 to -3 (LLDVPTAAV) is a prominent self peptide expressed with the class I human histocompatibility leukocyte antigen A2 (HLA-A2). Stimulation of peripheral blood mononuclear cells (PBMC) from HLA-A2 human immunodeficiency virus type 1 (HIV-1)-infected individuals with an HLA-A2-restricted HIV protease (PR) peptide 76-84 (LVGPTPVNI) activated cytotoxic T lymphocytes (CTL) against the IP-30 signal peptide. Since HIV-1 PR 76-84 stimulated CD8+ T cells from these individuals to secrete IFN-gamma, we tested whether the activation of IP-30-specific CTL in vitro resulted from T-cell cross-reactivity or from up-regulation of IP-30 by IFN-gamma.

Antiretroviral drug resistance mutations sustain or enhance CTL recognition of common HIV-1 Pol epitopes.

Antiretroviral drug resistance and escape from CTL are major obstacles to effective control of HIV replication. To investigate the possibility of combining drug and immune-based selective pressures against HIV, we studied the effects of antiretroviral drug resistance mutations on CTL recognition of five HIV-1 Pol epitopes presented by common HLA molecules. We found that these common drug resistance mutations sustain or even enhance the antigenicity and immunogenicity of HIV-1 Pol CTL epitopes.

Factors related to loss of HIV-specific cytotoxic T lymphocyte activity.

Objective: To identify factors associated with loss of in vitro stimulated anti-HIV cytotoxic T lymphocyte (CTL) activity.

Methods: Immunological, virological and other characteristics of individuals who sustained anti-HIV CTL activity for prolonged periods with viral replication suppressed below detectable levels were compared with those that lost anti-HIV CTL activity under the same circumstances. Forty-four individuals, all but one receiving highly active antiretroviral therapy or combination therapy, were followed for 56 months.

Lack of CD28 expression on HIV-specific cytotoxic T lymphocytes is associated with disease progression.

During HIV infection, CD8+ T cells lacking the costimulatory molecule CD28 increase in number and proportion. This accumulation is associated with disease activity and possibly with CD8+ T-cell dysfunction. In this study, CD8+CD28+ and CD8+CD28- T cells from 41 HIV-infected individuals at various stages of disease were compared in terms of HIV-specific cytotoxicity, TCR beta V repertoire diversity, and cytokine production.

Extrapyramidal symptoms with ritonavir/indinavir plus risperidone.

Objective: To report a case of suspected extrapyramidal symptoms (EPS) in a patient initiated on ritonavir and indinavir while taking risperidone for a tic disorder.

Case Summary: A 35-year-old white man with AIDS received risperidone 2 mg twice daily for treatment of a Tourette's-like tic disorder. Ritonavir and indinavir were initiated, and 1 week later, he experienced significantly impaired swallowing, speaking, and breathing, and worsening of his existing tremors.

Fas/FasL-independent activation-induced cell death of T lymphocytes from HIV-infected individuals occurs without DNA fragmentation.

We assessed the effects of activation with phorbol myrystic acetate (PMA) and ionomycin on peripheral blood mononuclear cells (PBMC) from HIV-infected individuals by (51)Cr release, propidium iodide (PI) uptake, electron microscopy, and DNA analysis. Up to 70% (51)Cr release was induced from PBMC of HIV-infected individuals, versus up to 26% (51)Cr release from PBMC of non-HIV-infected volunteers. Flow cytometry identified mostly T cells undergoing activation-induced cell death (AICD).

HIV-1 DNA burden in peripheral blood CD4+ cells influences disease progression, antiretroviral efficacy, and CD4+ T-cell restoration.

Integration of human immunodeficiency virus type-1 (HIV-1) proviral DNA into host cell genomic DNA ensures viral persistence despite suppression of active replication. Because HIV RNA originates from integrated HIV DNA, HIV RNA and DNA loads should interrelate when suppression of viral replication is incomplete. In addition, the link between proviral DNA formation and generation of HIV-1 genetic diversity suggests that the ease with which HIV escapes immune or drug-based suppression should vary with proviral load.

Functional and genetic integrity of the CD8 T-cell repertoire in advanced HIV infection.

Background: HIV-specific cytotoxic T lymphocytes (CTL) can restrict HIV replication in acute and chronic infection, but disease progression occurs in parallel with declining CTL activity. An understanding of why CTL fail to control HIV replication might reveal important mechanisms of disease progression and enhance prospects for developing effective CTL-based immunotherapies.

Objectives: To investigate the functional integrity, T-cell repertoire diversity, and HIV reactivity of CD8 T lymphocytes in individuals with advanced HIV infection.

Accreditation of postgraduate medical education in the United States and Canada: a comparison of two systems.

The systems for accrediting residency programmes in the United States and Canada, although they have developed independently in the two countries, have similar objectives and accreditation requirements. Both have become increasingly focused over the past several decades on the importance of educational programmes structured to provide graded professional responsibility with appropriate guidance and supervision to residents according to their level of training, ability and experience. The Canadian model used by the Royal College of Physicians and Surgeons of Canada is a centrist one, with accreditation decisions on all programmes in all specialties being vested in a single, multidisciplinary accreditation committee.

Single-dose ceftriaxone for chancroid.

Men with genital ulcers that were culture positive for Haemophilus ducreyi were treated with intramuscular ceftriaxone and randomized to three different dose regimens. All but 1 of 50 men treated with 1 g of intramuscular ceftriaxone were cured. Similarly, 0.

Factors affecting Staphylococcus epidermidis growth in peritoneal dialysis solutions.

Staphylococcus epidermidis is the most frequent cause of peritonitis complicating continuous ambulatory peritoneal dialysis. We studied factors that might influence the growth of S. epidermidis in commercially available peritoneal dialysis solution (PDS).

Von Hippel-Lindau disease in a Newfoundland kindred.

Von Hippel-Lindau disease, an autosomal dominant condition with complete penetrance, has been recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead.

Treatment of pneumonia and other serious bacterial infections with cephapirin.

Nineteen patients with pneumonia due to Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, or Escherichia coli were treated with 4 to 18 g of cephapirin daily. There were three treatment failures. One patient each with pneumonia due to E.