Biomedical subjects

T Le

Publications and source records attributed to T Le.

At least 109 records · Page 6Linked to original sources

PubMed1997

Controlled gene gun delivery and expression of DNA within the cornea.

Selective delivery of genes to ocular tissues in vivo has been a long sought after goal for potential gene therapy of ocular disease. The gene gun was considered for this purpose because of its ability to focally transfer DNA to cells through gold microparticles coated with DNA. Through experimentation, we optimized a technique that allows focal delivery and expression of a plasmid encoding green fluorescent protein in the corneal epithelium 100% of the time. Though the corneal epithelium has a delicate structure, this introduction was not associated with any corneal or ocular damage and did not produce any apparent ocular irritation. These findings demonstrate the utility of gene gun delivery of DNA to selected ocular tissues for potential experimental and therapeutic purposes.

Animals↗

PubMed1996

Preferential radiosensitization of G1 checkpoint-deficient cells by methylxanthines.

PURPOSE: To develop a checkpoint-based strategy for preferential radiosensitization of human tumors with deficient and/or mutant p53. METHODS AND MATERIALS: A549 human lung adenocarcinoma cell lines differing in their expression of the p53 tumor suppressor gene were produced by transduction with the E6 oncogene from human papilloma virus type 16. The cells expressing E6 (E6+) lack a G1 arrest in response to ionizing radiation, are deficient in p53 and p21 expression, and exhibit a fivefold greater clonogenic survival following 10 Gy radiation. RESULTS: Postirradiation incubation with millimolar concentrations of the methylxanthine pentoxifylline (PTX) results in preferential radiosensitization of the E6+ cells compared to the LXSN+ vector transduced controls. There is a threefold sensitization of the LXSN+ cells and a 15-fold sensitization of the E6+ cells, which results in equal clonogenic survival of the two lines. Flow cytometry reveals PTX abrogation of the radiation induced G2 arrest for both cell lines. PTX also prolongs G1 transit for both cell lines. Preliminary results are presented using a novel methylxanthine, lisofylline (LSF), which has similar cell cycle effects on G1 and G2 and achieves differential radiosensitization at micromolar concentrations that are sustainable in humans. CONCLUSION: This checkpoint-based strategy is a promising approach for achieving preferential radiosensitization of p53- tumors relative to p53+ normal tissues.

Cell Survival↗

PubMed1996

Health care access and preventive care among Vietnamese immigrants: do traditional beliefs and practices pose barriers?

Some have speculated that underutilization of Western health services among non-Western populations can be explained by traditional health beliefs and practices rooted deep within cultures. These beliefs and practices may act as barriers to access to and utilization of services. Among Vietnamese, in particular, a number of traditional health beliefs and practices have been identified which are said to pose barriers to Western medical care. No studies to date, however, have examined this hypothesis empirically. To examine this hypothesis, we measured traditional health beliefs and practices among Vietnamese in the San Francisco Bay area and analyzed the relationships between these factors and access to health care and use of preventive health services. The results of this study show clearly that many Vietnamese possess traditional health beliefs and practices which differ from those of the general U.S. population. Yet, the data do not support the hypothesis that these traditional beliefs and practices act as barriers to access to Western medical care or to utilization of preventive services. Being married and poverty status were the most consistent predictors of health care access. Furthermore, the components of access to health care (having some form of health insurance or having a regular doctor, for example) were the strongest predictors of preventive health care services utilization. Importantly, the cultural attributes of individuals did not explain either lack of health care access or underutilization of preventive health care services.

Adult↗

PubMed1996

Radioiodinated (aminostyryl)pyridinium (ASP) dyes: new cell membrane probes for labeling mixed leukocytes and lymphocytes for diagnostic imaging.

We prepared [125I/131I]iodo-(aminostyryl)pyridinium dyes from tributylstannyl precursors. ASP 7a and 7b labeled leukocytes ex vivo (70-94%) using saline with or without washing plasma from cells. Viability of peripheral blood lymphocytes (PBLs) (dogs, rats) and splenic lymphocytes (rats) labeled with 7a and 7b (71-82%) was unchanged after labeling (> or = 88%). Canine 7b-leukocytes showed higher uptake in inflammatory lesions than did 111In-oxine leukocytes. At 3 h, aspirates contained more radioiodine than 111In (1.65:1 to 22:1) and radioiodine was cell bound. ROI measurements (3 h) gave abscess to contralateral knee ratios of 12.3 and 10.6 for 131I-7b vs. 4.8 and 2.3 for 111In-oxine.

Animals↗

PubMed1996

Pattern of utilization of rifabutin for prophylaxis of Mycobacterium avium complex among patients with advanced human immunodeficiency virus disease in a community setting.

OBJECTIVE: To characterize the pattern of utilization, effectiveness, and safety profile of rifabutin for Mycobacterium avium complex (MAC) prophylaxis among individuals with advanced human immunodeficiency virus disease in a community setting. METHODS: Individuals who, while registered in the provincial drug distribution program, had at least one CD4 count below 100 cells/mm3 for the period 1 May 1993 to 31 March 1994 were included. MAC diagnoses were identified through a record linkage with the mycobacterial reference laboratory of the Provincial Centre for Disease Control. In order to determine the occurrence of adverse events, a survey was sent in March 1994 to the 98 primary care physicians prescribing rifabutin prophylaxis in the province. We achieved 100% response rate to the survey. RESULTS: During the study period 515 patients in our drug treatment program were eligible to receive MAC prophylaxis. Of these, 340 (66%) were being prescribed rifabutin as recommended by current guidelines. Rifabutin prophylaxis use was significantly associated with use of antiretroviral therapy. The product limit estimate of the cumulative incidence of MAC at 10 months was 13.0% among those receiving rifabutin prophylaxis. Diagnosis of MAC was significantly associated with a lower baseline CD4 count (cumulative incidence 7.1% and 18.1% for CD4 > or = 50 and < 50 cells/mm3, respectively, P = 0.01). A total of four cases of uveitis, eight cases of pseudo-jaundice, and five cases of arthralgia in 16 patients were identified by our survey. CONCLUSION: Our data demonstrates that rifabutin prophylaxis of MAC is being used by approximately 66% of eligible individuals. Rifabutin use was associated with antiretroviral use, which may reflect individuals' attitudes towards medications. Our intention-to-treat analysis, with a 10 month cumulative MAC incidence of 13.0% among those receiving rifabutin prophylaxis, is in keeping with break-through rates previously reported in the context of clinical trials. Our results also support previous observations that the risk of MAC infection greatly increases at CD4 counts < 50 cells/mm3. Rifabutin prophylaxis was generally well-tolerated in our program.

AIDS-Related Opportunistic Infections↗

PubMed1996

Functional and physical interactions between the Epstein-Barr virus (EBV) proteins BZLF1 and BMRF1: Effects on EBV transcription and lytic replication.

The Epstein-Barr virus (EBV) proteins BZLF1 and BMRF1 are both essential for lytic EBV replication. BZLF1 is a transcriptional activator which binds directly to the lytic origin of replication (oriLyt) and plays a critical role in the disruption of viral latency. The BMRF1 protein is required for viral polymerase processivity. Here we demonstrate that the BMRF1 gene product functions as a transcriptional activator and has direct (as well as indirect) interactions with the BZLF1 gene product. The BMRF1 gene product activates an essential oriLyt promoter, BHLF1, but does not activate two other early EBV promoters (BMRF1 and BHRF1). Direct interaction between the BMRF1 and BZLF1 gene products requires the first 45 amino acids of BMRF1 and the bZip domain of BZLF1. The effect of the BZLF1-BMRF1 interaction on early EBV transcription is complex and is promoter specific. The oriLyt BHLF1 promoter is activated by either the BZLF1 or BMRF1 gene product alone and is further activated by the combination of the BZLF1 and BMRF1 gene products. Enhanced activation of BHLF1 transcription by the BMRF1-BZLF1 combination does not require direct interaction between these proteins. In contrast, BZLF1-induced activation of the BMRF1 promoter is inhibited in the presence of the BMRF1 gene product. A point mutation in the BZLF1 protein (amino acid 200), which prevents in vitro interaction with the BMRF1 protein but which does not reduce BZLF1 transactivator function, allows the BZLF1 protein to activate the BMRF1 promoter equally well in the presence or absence of the BMRF1 gene product. Therefore, direct interaction between the BZLF1 and BMRF1 proteins may inhibit BZLF1-induced transcription of the BMRF1 promoter. BZLF1 mutated at amino acid 200 is as efficient as wild-type BZLF1 in promoting replication of an oriLyt plasmid. However, this mutation reduces the ability of BZLF1 to induce lytic replication of the endogenous viral genome in D98/HE-R-1 cells. Our results indicate that functional and physical interactions between the BMRF1 and BZLF1 proteins may modulate the efficiency of lytic EBV infection. The BMRF1 gene product clearly has a transcriptional, as well as replicative, role during lytic EBV infection.

Antigens, Viral↗

PubMed1996

An analysis of sampling errors for the Demographic Health Surveys.

"Sampling errors and design effects from 48 nationally representative surveys conducted under the Demographic and Health Surveys Program for a large number of variables concerning fertility, family planning, fertility intentions, child health and mortality etc. are analysed for the total sample, and for urban-rural domains, sub-national regions and various demographic and socio-economic subclasses.... At the country level, overall design effect (the ratio of actual to simple random sampling standard error) averaged over all variables and countries is around 1.5. Variation among countries is high, but less so than among variables. Urban-rural and regional differentials in design effects are small, and can be attributed to the fact that similar sample designs and cluster sizes were used across those domains within each country. Design effects for estimates over other subclasses are smaller, and tend towards 1.0 for small subclasses and differences, apart from the effect of sample weights which tends to persist undiminished across variables and subclasses." (SUMMARY IN FRE)

Child Welfare↗

PubMed1996

Bryostatin 1 acts synergistically with interleukin-1 alpha to induce secretion of G-CSF and other cytokines from marrow stromal cells.

The protein kinase C (PKC) activator bryostatin 1 (bryo) has substantial antileukemic and hematopoietic actions. Bryo promotes the in vitro growth of normal hematopoietic progenitors by inducing the release of growth factors from accessory cells. We have examined the effects of bryo on the expression and release of certain myeloid growth factors from fibroblastlike marrow stromal cells (MSC). Substantial release of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF). or interleukin-6 (IL-6) following bryo treatment was seen only in MSC cultures contaminated with macrophages. Bryo alone was ineffective in inducing release of the cytokines from MSC cultures containing only fibroblastlike stromal cells. When MSC were treated with IL-1alpha, substantial quantities of the cytokines (G-CSF, GM-CSF,IL-6) were released. Bryo acted synergistically with IL-1 alpha to significantly increase cytokine release to- to nine-fold compared to IL-1alpha alone (p < 0.016). Neither Il-1alpha nor bryo, alone or in combination, induced release of stem cell factor (scf) from MSC. The synergistic interaction between IL-1alpha and bryo was dose- and schedule-dependent, requiring simultaneous application of IL-1alpha and bryo for optimum effect. Bryo alone induced no G-CSF mRNA accumulation but increased the level seen with IL-1alpha treatment by 50%. The synergistic interaction of bryo and IL-1alpha required PKC, since it was antagonized by agents which depleted or inhibited PKC but not by a protein kinase A antagonist. The increase in G-CSF mRNA was associated with a marked increase in mRNA stability. Bryostatin may promote the release of cytokines from several accessory cell populations, including MSC, to accomplish its in vivo hematopoietic effects.

Bone Marrow↗

PubMed1995

Identification of a putative steroidogenic factor-1 response element in the DAX-1 promoter.

The nuclear hormone receptor, DAX-1, is responsible for X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism. We recently cloned the 5' flanking region of the human DAX-1 gene and in this report we describe the identification of a putative steroidogenic factor 1 (SF-1) response element approximately 110 bases upstream of the TATA box. Both DAX-1 and SF-1 are expressed in similar tissues including the adrenal cortex, gonads, hypothalamus, and the pituitary gland. Like DAX-1, SF-1 expression has been shown to be essential for the development of the adrenal cortex. We demonstrate that SF-1 is able to efficiently bind to the putative SF-1 response element found in the DAX-1 promoter in vitro. This suggests that SF-1 may directly regulate the expression of DAX-1 and that these two transcription factors may be components of a cascade required for development of steroidogenic tissues.

Base Sequence↗

PubMed1995

Patterns of cytokine secretion by autoreactive proteolipid protein-specific T cell clones during the course of multiple sclerosis.

To determine whether cytokine secretion patterns change with disease status in patients with multiple sclerosis (MS), we measured IFN-gamma, TNF-alpha beta, IL-4, IL-6, IL-10 and TGF-beta secretion in a panel of T cell clones (TCCs) specific for proteolipid protein (PLP) after stimulation with PLP peptides or polyclonal activators. During acute attack, the predominant pattern of cytokine secretion resembled that of murine Th1 cells; i.e, IFN-gamma and TNF-alpha beta, and appeared to be restricted to PLP-reactive TCCs. None of the TCCs isolated during acute attack produced TGF-beta in response to PLP, Con A, or anti-CD3 Ab. Half of these TCCs were, however, capable of TGF-beta secretion and mRNA expression upon stimulation with PMA and the calcium inonphore A23187, suggesting a possible defect in activation through the TCR/CD3 pathway. During remission in the same patients all but two PLP-TCCs showed patterns of cytokine secretion resembling that of murine Th0, Th1, and Th2 subsets. The levels of IL-10 secreted by these TCCs were significantly higher than those of TCCs isolated during acute attacks and those derived from normal subjects and patients with other noninflammatory neurologic diseases. Furthermore, 50% of these TCCs were capable of producing TGF-beta after Ag-specific or polyclonal stimulation. All TCCs isolated from control subjects exhibited a Th0 like secretion profile. These data indicate that different stages of disease in MS are characterized by different patterns of cytokine secretion by PLP-specific TCCs, suggesting a role for cytokines in clinical events during the course of MS.

Autoantigens↗

PubMed1995

Crystallization of the chaperone protein SecB.

The secretory protein SecB found in Escherichia coli is a molecular chaperone that binds to precursor forms of a number of proteins targeted for export to the periplasmic space. SecB maintains these proteins in a translocation-competent conformation facilitating the translocation process. The material has been cloned and expressed in E. coli. Crystals have been grown from polyethylene glycol 8000 by vapor diffusion using the hanging drop technique. These crystals are monoclinic, belonging to space group C2 with unit cell dimensions a = 56.0 A, b = 111.1 A, c = 134.7 A, and beta = 104 degrees. The crystals diffract to 8 A resolution on a Rigaku imaging plate detector. Dynamic light scattering experiments suggest that SecB exhibits aggregation behavior with a number of different precipitating agents. These results may explain resistance of SecB to forming ordered crystals.

Bacterial Proteins↗

PubMed1995

Hapten-induced chronic colitis in the rat: alternatives to trinitrobenzene sulfonic acid.

Hapten-induced colitis is a widely used model for the study of the intestinal inflammation and for the testing of novel therapies. However, the hapten utilized in this model, trinitrobenzene sulfonic acid, is difficult to obtain in some countries. We therefore compared this hapten to two structurally related haptens to determine if they could be substituted for trinitrobenzene sulfonic acid in terms of inducing chronic colitis in the rat. Rats received one of the three haptens intracolonically, and the severity of colonic inflammation was assessed 3 and 14 days later. Dinitrobenzene sulfonic acid produced colonic inflammation and ulceration that was indistinguishable from that induced by trinitrobenzene sulfonic acid at both time points. On the other hand, dinitrochlorobenzene produced acute colitis (3 days postadministration), but by Day 14 this inflammation had subsided. Dinitrobenzene sulfonic acid and trinitrobenzene sulfonic acid produced comparable levels of granulocyte infiltration into the colon (as measured by tissue myeloperoxidase activity and histology) at both time points. These studies suggest that for studies of up to at least 2 weeks in duration, dinitrobenzene sulfonic acid and trinitrobenzene sulfonic acid produce comparable levels of colonic inflammation. Dinitrobenzene sulfonic acid therefore offers a useful and less expensive alternative to trinitrobenzene sulfonic acid.

Animals↗

PubMed1995

Use of pooling and outpatient laboratory specimens in an anonymous seroprevalence survey of HIV infection in British Columbia, Canada.

OBJECTIVE: To conduct an anonymous HIV seroprevalence survey to establish a baseline estimate of HIV seroprevalence in a general population; to evaluate serum pooling and alternative testing strategies as cost-saving measures. DESIGN: Prospective anonymous HIV seroprevalence study using outpatient laboratory specimens. SETTING: Two large non-hospital-associated outpatient chemistry testing laboratories in the major population centers in British Columbia, Canada. PATIENTS AND SERA: Leftover sera received for chemistry screen testing in outpatient laboratories were provided to the study after chemistry testing was completed. Those from patients aged < 15 and > or = 55 years were excluded. METHODS: Patient identifiers were erased from samples. Sera were pooled 10:1 and tested by viral lysate enzyme-linked immunosorbent assay (ELISA). Sera from HIV-positive pools were tested individually. All individual HIV-positive specimens were retested for verification of positivity using a recombinant protein ELISA. MAIN OUTCOME MEASURES: HIV seroprevalence rates were stratified by sex, age group, and geographic area; and costs of pooling and alternative algorithm strategy were compared with those of conventional methods. RESULTS: A total of 80,238 sera were collected from 66,658 individuals (53% women, 47% men). Of these, 276 men (88.3 per 10,000) and 24 women (6.8 per 10,000) were HIV-seropositive. The highest rates were in those aged 30-34 years, for both men and women. Using pooling and non-Western blot verification saved US$2.07 per specimen, or 80% of the cost for conventional testing. CONCLUSIONS: The anonymous outpatient laboratory setting is practicable to obtain a reasonable estimate of HIV seroprevalence rates in a general population. Such studies can be made cost-effective by pooling sera and using alternative confirmatory strategies.

AIDS Serodiagnosis↗

PubMed1995

Isolation and characterization of autoreactive proteolipid protein-peptide specific T-cell clones from multiple sclerosis patients.

During the course of multiple sclerosis (MS), myelin proteins are likely antigenic targets for autoreactive T cells. Although most studies have implicated myelin basic protein as a potent encephalitogenic myelin component, proteolipid protein (PLP) appears also to be a possible target antigen in the autoimmune response in MS. In this report, we investigated the human T-cell responses to PLP by using PLP104-117 and PLP142-153 synthetic peptides as target antigens in limiting dilution. One hundred twenty-five CD4+, T-cell receptor (TCR) alpha beta+ T-cell clones (TCCs) were established from the peripheral blood of seven MS patients and five control subjects. Despite the use of enriched cultures no gamma delta TCCs were obtained. Recognition of both PLP epitopes occurred in the context of multiple HLA-DR alleles. We found no differences in restriction element usage between MS patients and control subjects. TCR variable beta-region (V beta) usage was assessed by flow cytometry using a panel of monoclonal antibodies defining different V beta elements. In both MS patients and control subjects, there was a marked heterogeneity in the TCR V beta repertoire. Furthermore, sequential evaluation of MS patients during acute attacks and clinical remissions showed even more broadening of the TCR V beta repertoire. These data demonstrate that a heterogeneous T-cell response to PLP concerning HLA restriction and TCR usage is present in both MS patients and normal subjects.

Adult↗

PubMed1994

Possible mechanisms accounting for the growth factor independence of hematopoietic progenitors from umbilical cord blood.

Hematopoietic progenitors obtained from the bone marrow of healthy adults fail to undergo clonogenic maturation in vitro if a source of hematopoietic growth factors is not included in the culture dishes. In contrast, a fraction of similarly purified progenitors obtained from umbilical cord blood undergo clonogenic maturation even in the absence of added growth factors. We postulated that production of hematopoietic growth factors within the culture dishes containing the progenitors of umbilical cord blood origin might be responsible. We postulated further, that this production might be by non-progenitor cells co-plated along with the progenitors, or alternatively by CD34+ cells themselves, or by cells clonally derived from CD34+ cells. To test these possibilities we first assessed the effect of including in the cultures neutralizing antibody directed against various growth factors. Inclusion of anti-granulocyte macrophage colony-stimulating factor (GM-CSF) and anti-interleukin-3 (IL-3) (but not anti-IL-2) significantly reduced the growth factor independence of cord blood progenitors (P < .005 and P < .01). Inclusion of both anti-GM-CSF and anti-IL-3 almost completely ablated the spontaneous colony growth (P < .001). Inclusion of IL-10 also reduced, in a concentration-dependent fashion, the spontaneous generation of umbilical cord blood-derived colonies. Transcripts for GM-CSF and IL-3 were detected, by reverse transcriptase-polymerase chain reaction (RT-PCR), in the CD34+ cells from cord blood and from adult marrow. When plated without added growth factors, however, the CD34+ cells of adult marrow origin failed to produce colonies, whereas 6% of cord blood CD34+ cells similarly cultured did so. When these growth factor independent colonies were plucked from culture, transcripts for GM-CSF and IL-3 were identified in all. We conclude that production of GM-CSF and IL-3 occurs within culture dishes containing hematopoietic progenitors of umbilical cord origin, and that this explains some of their apparently unique features of in vitro growth.

Adult↗

PubMed1994

Specific transforming growth factor-beta subtypes regulate embryonic mouse Meckel's cartilage and tooth development.

Members of the transforming growth factor-beta (TGF-beta) superfamily have emerged as critical regulators for cell growth and differentiation. Whereas the different TGF-beta subtypes are equipotent in the majority of biological assays using cell lines cultured in vitro, there are indications that in more complex systems involving epithelial-mesenchymal interactions, the TGF-beta subtypes differ in their biological activities. To test the hypothesis that TGF-beta subtypes specifically regulate either Meckel's cartilage or tooth morphogenesis, we designed experiments to compare loss of function effects of TGF-beta 1, TGF-beta 2, and TGF-beta 3 subtypes using a serumless, chemically defined medium to culture embryonic mouse E10 (42-44 somite pairs) mandibular explants. The major effect of loss of function resulting from abrogation of TGF-beta 1 using antisense treatment resulted in a 20% increase (P < 0.05) in chondrocyte number, a decrease in extracellular matrix, and dysmorphology of the rostral region of Meckel's cartilage. Exogenous TGF-beta 1 provided indistinguishable recovery to the normal phenotype. TGF-beta 2 antisense treatment produced a threefold enlargement (P < 0.05) of tooth organs and advanced their development to the cap stage. TGF-beta 2 provided recovery to the normal phenotype (e.g., reduced tooth size and development to the bud stage), whereas TGF-beta 1 or TGF-beta 3 polypeptides had no effect. TGF-beta 3 antisense treatment resulted in a reduction of approximately 15% in the length of Meckel's cartilage. We interpret these results to suggest that TGF-beta 1 functions to regulate the number of chondrogenic cells, the amount of extracellular matrix, and the rate of developmental assembly of the rostral to posterior segments in forming Meckel's cartilage. TGF-beta 2 appears to regulate tooth size and stage of development without affecting cartilage. TGF-beta 3 appears to regulate Meckel's cartilage size without altering tooth size or shape. The results are discussed in terms of the regulatory functions of the TGF-beta subtypes during embryonic craniofacial morphogenesis.

Animals↗

PubMed1994

Sperm-egg recognition in the mouse: characterization of sp56, a sperm protein having specific affinity for ZP3.

Recognition between mammalian gametes occurs when the plasma membrane of the sperm head binds to the zona pellucida (ZP), an extracellular coat surrounding eggs. ZP3, one of three glycoproteins in the ZP, is the egg protein recognized by sperm. A mouse sperm surface protein, sp56 (M(r) = 56,000), has been identified on the basis of its specific affinity for ZP3 (Bleil, J. D., and P. M. Wassarman. 1990. Proc. Natl. Acad. Sci. USA. 87:5563-5567). Studies presented here were designed to characterize mouse sperm sp56 and to further test whether or not this protein specifically recognizes ZP3. sp56 was purified by both ZP3 affinity chromatography and by ion exchange chromatography followed by size-exclusion chromatography. The purified native protein eluted from size-exclusion columns as a homomultimer (M(r) approximately 110,000). Each monomer of the protein contains intramolecular disulfide bonds, consistent with its extracellular location. Immunohistochemical and immunoblotting studies, using monoclonal antibodies, demonstrated that sp56 is a peripheral membrane protein located on the outer surface of the sperm head plasma membrane, precisely where sperm bind ZP3. Results of crosslinking experiments demonstrated that the ZP3 oligosaccharide recognized by sperm has specific affinity for sp56. Collectively, these results suggest that sp56 may be the sperm protein responsible for sperm-egg recognition in the mouse.

Amino Acid Sequence↗

PubMed1994

The changing spectrum of AIDS index diseases in Canada.

OBJECTIVE: To describe the changing spectrum of AIDS index diseases in Canada over a 10-year period from 1981 to 1991. DESIGN: A descriptive, population-based study. SETTING: Canada. PATIENTS: All cases of AIDS in Canada reported by the Division of HIV/AIDS Epidemiology of the Department of National Health and Welfare. MAIN OUTCOME MEASURES: Age-standardized rates of initial AIDS manifestations (1987 Centers for Disease Control and Prevention case definition), by year of diagnosis among adults in Canada. RESULTS: A total of 6641 adult AIDS cases were examined. The rate of Pneumocystis carinii pneumonia (PCP) peaked in 1989 with a rate of 3.18 per 100,000, declining to 2.74 per 100,000 in 1991 (P = 0.894). Similarly, the rate of Kaposi's sarcoma (KS) stabilized during this interval from 1.06 per 100,000 in 1987 to 1.14 per 100,000 in 1991 (P = 0.189). In contrast, the rates of all other AIDS-defining illnesses increased from 1.48 per 100,000 in 1987 to 3.43 per 100,000 in 1991 (P = 0.001). For these other AIDS index diseases, significant rate increases were observed for esophageal candidiasis, cytomegalovirus (CMV) diseases, wasting syndrome, toxoplasmosis, and Mycobacterium avium complex (MAC) disease. CONCLUSIONS: Our study shows a leveling and decline in incidence of KS and PCP, respectively, and a concomitant increase of other diagnoses, especially esophageal candidiasis, CMV, wasting syndrome, toxoplasmosis, and MAC disease in Canada. These findings highlight the importance of developing specific strategies to prevent emerging AIDS index diseases and serve as a cautionary note to practicing clinicians, indicating the relative widening of the spectrum of HIV index diseases.

AIDS-Related Opportunistic Infections↗