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Biomedical subjects

B Chan

Publications and source records attributed to B Chan.

At least 55 records · Page 3Linked to original sources
PubMed1998

The economic cost of musculoskeletal disorders in Canada.

OBJECTIVE: This study estimated the total cost of musculoskeletal disorders for Canadians in 1994 and assessed the sensitivity of these cost estimates to variations in the definition of musculoskeletal disorders. METHODS: Disease-related costs, from a societal perspective, were measured using a prevalence-based analysis. First, direct treatment costs, including expenditures on hospitals and other institutions, physicians and other health professionals, drugs, research, and other items were assessed. Second, indirect costs associated with lost (or foregone) productivity due to disability and premature mortality were evaluated using the human capital approach. RESULTS: The total cost of musculoskeletal disorders in Canada was $25.6 billion (in 1994 Canadian dollars, $1.00 CDN approximately $0.75 US) or 3.4% of the gross domestic product. Direct and indirect costs were estimated at $7.5 billion and $18.1 billion, respectively. Lower and upper bound estimates of the total cost of musculoskeletal disorders, derived from the sensitivity analysis, were $19.9 billion and $30.8 billion, respectively. Wide variations were reported in the total cost of various musculoskeletal disorder subcategories, with the highest costs reported for injuries ($10.7 billion), back and spine disorders ($8.1 billion), and arthritis and rheumatism ($5.9 billion). CONCLUSIONS: The economic cost of musculoskeletal disorders was substantial and was sensitive to the definition of musculoskeletal disorders and other underlying assumptions. The hallmark of this study was the variation between subcategories in their cost, pattern of health resource use, and sequelae. The cost estimates may provide guidance in setting priorities for research and prevention activities.

Canada↗
PubMed1998

Variations in mental health needs and fee-for-service reimbursement for physicians in Ontario.

OBJECTIVES: The study examined the match between mental health needs and physician fee-for-service reimbursements for mental health care within age and gender groups and health planning regions in Ontario, Canada. METHODS: Indicators of need (mental disorder, reported disability, and self-rated mental health) from an epidemiologic survey of 9,953 Ontario household residents were compared with per capita reimbursement rates derived from an administrative data set containing all fee-for-service expenditures for mental health care paid by the provincial health plan. RESULTS: Few gender differences were found in overall need, but need varied significantly by age. Those in greatest need were adolescent males and females, who had rates of need from two to four times higher than older respondents. Regional variations in need were less evident. By contrast, per capita reimbursement showed marked gender differences, with rates for women generally twice the rates for men. Considerable variations in reimbursement were also found across age groups; these variations did not match variations in need. Highly urbanized areas had per capita reimbursement rates between two and four times the rates for less populated areas. CONCLUSIONS: Despite Ontario's universal-access health care system, notable discrepancies between need and resource use are evident for males, adolescents, and residents of less urbanized areas. Solutions require a combination of public education, provider training, attention to physician availability and practice patterns, and continuous monitoring of how resources are allocated relative to need.

Adolescent↗
PubMed1998

Idiopathic progressive hyalinizing and calcifying CNS vasculopathy.

We present a female adolescent with intermittently progressive neurologic deficits over a period of 7 years. Serial imaging studies showed a calcifying lesion with increasing enhancement, signal abnormalities from the subcortex to the medulla, and hemispheric volume loss. Stereotactic biopsies disclosed a hyalinizing and calcifying vasculopathy involving the penetrating vessels. The vasculopathy may result in ischemic lesions responsible for the severe deficits.

Adolescent↗
PubMed1997

The nucleocapsid protein specifically anneals tRNALys-3 onto a noncomplementary primer binding site within the HIV-1 RNA genome in vitro.

HIV type 1 (HIV-1) specifically uses host cell tRNALys-3 as a primer for reverse transcription. The 3' 18 nucleotides of this tRNA are complementary to a region on the HIV RNA genome known as the primer binding site (PBS). HIV-1 has a strong preference for maintaining a lysine-specific PBS in vivo, and viral genomes with mutated PBS sequences quickly revert to be complementary to tRNALys-3. To investigate the mechanism for the observed PBS reversion events in vitro, we examined the capability of the nucleocapsid protein (NC) to anneal various tRNA primer sequences onto either complementary or noncomplementary PBSs. We show that NC can anneal different full-length tRNAs onto viral RNA transcripts derived from the HIV-1 MAL or HXB2 isolates, provided that the PBS is complementary to the tRNA used. In contrast, NC promotes specific annealing of only tRNALys-3 onto an RNA template (HXB2) whose PBS sequence has been mutated to be complementary to the 3' 18 nt of human tRNAPro. Moreover, HIV-1 reverse transcriptase extends this binary complex from the proline-specific PBS. The formation of the noncomplementary binary complex does not occur when a chimeric tRNALys/Pro containing proline-specific D and anticodon domains is used as the primer. Thus, elements outside the acceptor-TPsiC domains of tRNALys-3 play an important role in preferential primer use in vitro. Our results support the hypothesis that mutant PBS reversion is a result of tRNALys-3 annealing onto and extension from a PBS that specifies an alternate host cell tRNA.

Base Sequence↗
PubMed1997

Spirometry utilization in Ontario: practice patterns and policy implications.

OBJECTIVE: To describe growth and regional variation in the use of spirometry (flow studies) in Ontario. DESIGN: Retrospective analysis of Ontario Health Insurance Plan (OHIP) fee-for-service billing data for spirometry from the 1989-90 to 1994-95 fiscal years. SETTING: Physicians' office practices in Ontario. OUTCOME MEASURES: Number of flow studies and associated expenditures, number and specialty of physicians performing flow studies and the distribution of their billings, number of studies per capita by age group of patients, expenditures by region and measures of variation among regions. RESULTS: In 1994-95, $14.13 million was spent on flow studies in Ontario. This expenditure increased by 36.9% from 1989-90 to 1994-95, exceeding the overall growth rate of 20.8% for all expenditures under OHIP. Expenditure growth was driven by an increase in the number of physicians performing spirometry rather than a higher volume of services performed per physician. The substitution of flow-volume loops, for which the fee is higher, for simple spirograms also contributed to expenditure growth. There were wide regional variations in spirometry utilization. A small number of general practitioners and family physicians accounted for much of the regional variation. CONCLUSIONS: The rapid growth in spirometry utilization may stem from the diffusion of inexpensive spirometers in physicians' offices and from increased awareness of guidelines promoting the use of flow measurements. However, the wide regional variation in utilization may indicate either incomplete implementation of spirometry guidelines or lack of direction on the appropriate frequency of spirometry use. Clearer, evidence-based guidelines and an implementation strategy are needed. Also required is further study of possible inadequate access to spirometry in low-use regions and inappropriate use in high-use regions, where spirometry use is concentrated among a small number of physicians.

Adolescent↗
PubMed1997

Economic consequences of multiple sclerosis for Canadians.

OBJECTIVES: To estimate the total costs of multiple sclerosis (MS) for all Canadians in 1994. METHODS: Prevalence-based study estimating disease-related societal costs for Canadians with MS in 1994. The human capital approach was used to estimate the value of lost productivity due to illness. Two components were revealed: first, direct costs, in terms of expenditures on hospital care, other institutions, physician services, other health professionals, drugs, and other expenditures; and second, indirect costs, in terms of lost productivity due to premature mortality and disability. RESULTS: The total costs of MS for Canadians were $502.3 million in 1994, with direct and indirect cost components at $188.6 million and $313.7 million, respectively. CONCLUSIONS: This study highlights the scope and magnitude of the economic consequences of MS for Canadians. The costs calculated may be used to provide guidance in the setting of national priorities for research and prevention activities.

Canada↗
PubMed1997

Murine CTLA4-IgG treatment inhibits airway eosinophilia and hyperresponsiveness and attenuates IgE upregulation in a murine model of allergic asthma.

Antigen-specific T-cell activation requires the engagement of the T-cell receptor (TCR) with antigen as well as the engagement of appropriate costimulatory molecules. One of the most important pathways of costimulation is the interaction of CD28 on the T cell with B7-1/B7-2 on antigen-presenting cells. In the present study, we have examined the in vivo effects of blocking the CD28:B7 T-cell costimulatory pathway by administration of mCTLA4-IgG in a murine model of allergic asthma. Mice were sensitized with ovalbumin and exposed to repeated ovalbumin inhalation challenges. In mice treated with a control antibody at the time of ovalbumin challenge a significant increase in the number of eosinophils (12.8 +/- 4.3 x 10(3) cells, P < 0.05) in the bronchoalveolar lavage (BAL) fluid and airway hyperresponsiveness to methacholine (49 +/- 15%, P < 0.05) was observed. In addition, serum levels of ovalbumin-specific IgE were significantly (P < 0.01) increased after ovalbumin challenge compared with saline challenge (1,133 +/- 261 experimental units [EU]/ml and 220 +/- 63 EU/ml, respectively). In mice treated with mCTLA4-IgG at the time of ovalbumin challenge, the infiltration of eosinophils into BAL fluid and the development of airway hyperresponsiveness to methacholine were completely inhibited. The upregulation of ovalbumin-specific IgE levels in serum was attenuated by mCTLA4-IgG treatment. Furthermore, addition of mCTLA4-IgG to cultures of parabronchial lymph node cells from sensitized mice inhibited the ovalbumin-induced interleukin-4 production. These data indicate the therapeutic potential of blocking T-lymphocyte costimulation by CTLA4-IgG as a possible immunosuppressive treatment for patients with allergic asthma.

Abatacept↗
PubMed1997

Is colour flow imaging needed to exclude clinically significant valvular regurgitation in adult patients undergoing transthoracic echocardiography?

OBJECTIVE: To establish whether clinically significant aortic and mitral valvular regurgitation can be excluded in adult patients undergoing transthoracic echocardiography without using colour flow imaging. SETTING: Sunnybrook Health Science Centre, a tertiary referral centre with full cardiovascular services affiliated with the University of Toronto, Toronto, Ontario. DESIGN: Logistic regression models were developed from a retrospective review of 14,051 unselected consecutive echocardiograms from 1991 through 1994. The dependent variable was more than mild aortic or mitral valvular regurgitation. Independent variables included age, sex and various functional and structural measures obtained during routine two-dimensional echocardiography. The negative predictive values and sensitivity of the models were estimated. INTERVENTION: The number of patients correctly classified by these models, as well as the proportion for whom the colour flow imaging did not add to the baseline echocardiogram, was determined. Nonparametric bootsrapping was used to obtain confidence intervals for these statistics. MAIN RESULTS: Ten models were developed, with negative predictive values ranging from 96.2% to 100%. Incorporation of such decision aids into the software of echocardiographic machinery would help echocardiographers to rule out significant aortic or mitral regurgitant lesions. In practices where colour flow imaging is routinely employed, 40% fewer procedures could be performed. CONCLUSIONS: Models based on simple demographic and two-dimensional echocardiographic variables can reliably exclude significant valvular regurgitation and could potentially reduce the volumes and costs of colour flow imaging. Given the widespread diffusion of colour Doppler imaging, the models may also be helpful to avoid misinterpretation of flow imaging results, by defining subgroups in whom the prior probability of significant aortic or mitral regurgitation is extremely low.

Aged↗
PubMed1997

The role of integrins and extracellular matrix in anchorage-independent growth of a mammary carcinoma cell line.

Anchorage-independent growth is a property of malignant cells. Extracellular matrix proteins are present in tumor spheroids but their function is not clearly defined. In this paper we show that a murine mammary carcinoma cell line, SP1, which expresses the fibronectin receptor alpha 5 beta 1 requires fibronectin for anchorage-independent growth in soft agar. Growth factors (hepatocyte growth factor and transforming growth factor-beta) also promote SP1 colony growth. In contrast, collagen types I and IV have an inhibitory effect on SP1 colony growth. A clone isolated from SP1 cells which expresses the collagen/laminin receptor alpha 2 beta 1 as well as the fibronectin receptor alpha 5 beta 1, demonstrates increased colony formation in the presence of fibronectin and collagen. These data suggest a role for both the alpha 5 beta 1 and alpha 2 beta 1 integrin receptors in the regulation of anchorage-independent growth of mammary carcinoma cells.

Animals↗
PubMed1996

Humanization of an anti-lymphocyte function-associated antigen (LFA)-1 monoclonal antibody and reengineering of the humanized antibody for binding to rhesus LFA-1.

Lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) is involved in leukocyte adhesion during cellular interactions essential for immunologic responses and inflammation. mAbs against LFA-1 have been shown to inhibit several T cell-dependent immune functions in vitro and prevent graft failure after bone marrow transplantation in vivo. A murine anti-human CD11a mAb, MHM24, has been humanized and shown to prevent adhesion of human T cells to human keratinocytes and the proliferation of T cells in response to nonautologous leukocytes in the mixed lymphocyte response assay. However, of the nonhuman primate CD11a that we tested, the murine and humanized mAbs cross-reacted only with chimpanzee CD11a. To have a mAb available for preclinical studies in rhesus monkeys, the humanized mAb was reengineered to bind to rhesus CD11a by changing four residues in one of the complementarity-determining regions, CDR-H2, in the variable heavy domain. Cloning and molecular modeling of rhesus CD11a I-domain suggested that the changes from Lys197 and/or Arg189 in human CD11a I-domain to Glu197 and Gln189 in rhesus CD11a I-domain may be the reason that rhesus CD11a does not bind to the murine and humanized mAbs.

Amino Acid Sequence↗
PubMed1996

Appropriateness of primary total hip and knee replacements in regions of Ontario with high and low utilization rates.

OBJECTIVE: To compare the appropriateness of case selection for primary hip and knee replacements between two regions in Ontario: one with a high population-based utilization rate and one with a low rate. DESIGN: Random audit of medical records sampled from hospital discharge abstracts, with subsequent implicit and explicit criteria-based assessments of the appropriateness of surgery. STUDY POPULATION: People aged 60 years or over who underwent elective, single-joint, non-fracture-related, primary hip or knee replacement between Apr. 1, 1992, and Mar. 31, 1993, at one of seven hospitals in a high-rate region (comprising Brant, Huron and Oxford countries) or one of eight hospitals in a low-rate region (comprising the cities of Scarborough and Toronto). INTERVENTIONS: Structured review of hospital medical records, with additional review of information from surgeons and family physicians' office charts if necessary. Three physicians reviewed patient data and rated the preoperative pain level and functional status of patients, with agreement among at least two reviewers. The proportion of inappropriate cases was then assessed according to explicit criteria defined by a multidisciplinary panel using the delphi process. Profiles of each case were also subjected to independent implicit review by two rheumatologists and two orthopedic surgeons. OUTCOME MEASURES: Proportion of joint replacements deemed inappropriate in the high- and low-rate regions according to either the explicit criteria or the implicit review, as well as preoperative pain levels and functional status of patients in the high- and low-rate regions. RESULTS: Hip replacements were more common among patients sampled in the low-rate region than among those in the high-rate region (57.3% v. 39.3%; p < 0.002), although the patients' baseline characteristics, including severity of preoperative pain and dysfunction, were otherwise similar between the regions. Inappropriate surgery, determined by explicit criteria, was equally uncommon in the two regions (6.4% and 6.1%). On implicit review, the two rheumatologists rated fewer cases as appropriate than did the two orthopedic surgeons (63.0% v. 80.0%; p < 0.001); however, the proportion of cases rated as inappropriate by the subspecialists was similar in the high- and low-rate regions (11.4% and 11.0%, respectively, by the rheumatologists, and 6.3% and 10.4%, respectively, by the orthopedic surgeons). CONCLUSIONS: Patients selected for primary hip or knee replacement are similar in the high- and low-rate regions of Ontario. Inappropriate use of this procedure does not account for the high rate of surgery in some areas. Further studies will be required to determine which other factors account for the regional variations in the utilization rates and whether there is underservicing in low-rate areas.

Chi-Square Distribution↗
PubMed1996

Cold air-induced bronchoconstriction is mediated by tachykinin and kinin release in guinea pigs.

In the present study, we investigated the role of acetylcholine, tachykinins and kinins in the bronchoconstriction induced by cold air inhalation. Cold air was delivered to anaesthetised, artificially ventilated guinea pigs through a tracheal cannula. Inhalation of cold air increased the maximum total pulmonary resistance (RL) in a time-dependent manner, reaching a maximum after 15 min of exposure. The increase in RL induced by exposure to cold air for 10 min was not affected by pretreatment with atropine (1.4 mu mol/kg, i.v.); it was abolished by the tachykinin NK2 receptor antagonist, SR 48968 (0.3 mu mol/kg, i.v.) and was reduced by 58% by the kinin B2 receptor antagonist, HOE 140 (0.1 mu mol/kg, i.v.). These findings suggest that cold air induces bronchoconstriction in guinea pigs via a cascade that involves the release of kinins and tachykinins.

Animals↗
PubMed1996

Assessment of the effect of candidate anti-inflammatory treatments on the interaction between meningococci and inflammatory cells in vitro in a whole blood model.

A wide range of immunomodulating agents are now available which may be of benefit in reducing inflammatory cell activation in meningococcal sepsis. In order to facilitate selection of candidate anti-inflammatory agents for clinical trials, we have used an in vitro whole blood model to evaluate the effects on meningococcal induced neutrophil and monocyte activation, of dexamethasone, prostacyclin, pentoxifylline and a human IgM anti-lipid A monoclonal antibody (HA-1A). Known concentrations of heat and penicillin killed meningococci were added to whole blood and the time course of cellular activation was determined. Using elastase alpha 1-antitrypsin (elastase-alpha 1-AT) and TNF alpha production as markers of neutrophil and monocyte activation respectively, plasma levels of elastase-alpha 1-AT and TNF alpha were found to increase in a dose-dependent manner. Elastase-alpha 1-AT was detected early, with most release occurring between 15-30 min whereas TNF alpha was detected later, between 120-180 min. Dexamethasone, prostacyclin and pentoxifylline caused a dose-dependent inhibition of TNF alpha release but had no effect on elastase release. HA-1A had no effect on either TNF alpha or elastase release. This model may be useful in determining the sequence of inflammatory cell activation and in selecting candidate anti-inflammatory agents for evaluation in clinical trials.

Anti-Inflammatory Agents↗
PubMed1996

Tachykinins mediate the potentiation of antigen-induced bronchoconstriction by cold air in guinea pigs.

The role of tachykinins in the potentiation of antigen-evoked bronchoconstriction induced by inhalation of cold air was studied in guinea pigs. Cold air was delivered through a tracheal cannula to anesthetized, artificially ventilated guinea pigs sensitized with ovalbumin and pretreated with atropine (1.4 micromol/kg). Inhalation of cold air increased total pulmonary resistance (RL) in a time-dependent manner; inhalation of cold air for 10 or 15 minutes, but not for 5 minutes, produced a significant increase in RL. Aerosolized ovalbumin (5 breaths) increased RL in a dose-dependent manner (0.5% to 5%). Inhalation of cold air for 5 minutes significantly enhanced both the peak and the duration of the increase in RL induced by 0.5% ovalbumin. The tachykinin neurokinin 2-receptor antagonist, SR 48968 (0.3 micromol/kg intravenously) inhibited both the peak and the duration of the bronchoconstriction induced by 5-minute inhalation of cold air and ovalbumin (0.5%), whereas it did not affect the response to ovalbumin (0.5%) alone. These findings suggest that exposure to cold air potentiates the bronchoconstriction response to antigen and that this potentiation is mediated by tachykinin release from sensory nerves.

Airway Resistance↗
PubMed1996

Trends in the utilization of noninvasive cardiac diagnostic tests in Ontario from fiscal year 1989/90 to 1992/93.

OBJECTIVE: To describe pattern of utilization of noninvasive cardiac diagnostic test in Ontario. DESIGN: Retrospective analysis using Ontario Health Insurance Plan (OHIP) administrative data. SETTING: Ambulatory care settings in Ontario. MAIN OUTCOME MEASURES: First, the volume of services and expenditures on electrocardiograms (ECG), ambulatory ECG, radionuclide angiocardiograms (RNA), echocardiograms, exercise stress tests (EST), and myocardial perfusion scintigrams from 1989/90 to 1992/93; second, the number and specialty of physicians performing these tests. MAIN RESULTS: Ontario spent $119 million on noninvasive diagnostic cardiology test in 1992/93, representing 2.67% of total OHIP expenditures. Expenditures on these procedures grew by 49.3 % over the four-year period, exceeding the overall OHIP growth rate, and was most rapid for nuclear cardiology and echocardiography. Changing demographics accounted fpr only a minor portion of expenditure growth. Second, age-adjusted utilization rates for EST, myocardial perfusion scintigraphy and RNA were higher for men, but sex differences tended to diminish over time. Third, utilization rates differed markedly by geographic region, and variations were greatest for nuclear medicine studies. Geographic variations tended to be attenuated over time. There was also wide variation in the frequency with which physicians performed Doppler studies with two-dimensional echocardiography. CONCLUSIONS: The use of noninvasive cardiac diagnostic test has grown rapidly in recent years. This growth may have been influenced by practice guidelines, by greater diffusion of, and access to, newer technology and by more testing in women. Wide regional variations suggest that clearer practice guidelines are needed concerning the appropriate use of noninvasive cardiac diagnostic investigations.

Angiocardiography↗
PubMed1996

Economic impact of cardiovascular disease in Canada.

OBJECTIVE: To estimate the total cost of cardiovascular disease in Canada. DESIGN: Prevalence-based study estimating disease-related costs generated by individuals with cardiovascular disease in 1994, from a societal viewpoint. The human capital approach was used to estimate the value of lost productivity due to illness. SETTING: Canada. OUTCOME MEASURES: First, direct costs, in terms of expenditures on hospital care, other institutions, physician services, other health professionals, drugs, research and other items; and second, indirect costs, in terms of lost productivity due to premature mortality or disability. MAIN RESULTS: The total cost of cardiovascular disease was $18.0 billion in 1994, with direct and indirect cost components at $10.4 and $7.6 billion, respectively. Based on the sensitivity analysis, the lower and upper bounds were $14.1 and $20.4 billion, respectively. CONCLUSIONS: This study highlights the scope and magnitude of cardiovascular disease through its economic consequences. While the figures calculated herein do not give an indication of the appropriateness of current health expenditures on cardiovascular disease, they provide guidance in the setting of national priorities for research and prevention activities.

Canada↗
PubMed1995

Corticotropin-releasing factor inhibits antigen-induced plasma extravasation in airways.

We investigated the potential of corticotropin-releasing factor (CRF) to reduce neurogenic plasma extravasation in sensitised guinea pig airways evoked by antigen challenge. Inhalation of 5% ovalbumin for 2 min in the presence of phosphoramidon (2.5 mg/kg, i.v.) increased extravasation of Evans blue dye in the trachea and main bronchi. The increase in plasma extravasation induced by antigen challenge was significantly reduced by pretreatment with CRF (30 nmol/kg, i.v.) (73% in the trachea and 42% in the main bronchi). The inhibition of plasma extravasation by CRF (30 nmol/kg, i.v.) alone was not different from the inhibition induced by the combination of CRF and the tachykinin NK1 receptor antagonist, CP-99,994 (4 mg/kg, i.v.) (73% in the trachea and 38% in the main bronchi). CRF (30 nmol/kg, i.v.) inhibited by 32% in the trachea and by 43% in the main bronchi plasma extravasation induced by aerosolised bradykinin but did not reduce the plasma extravasation caused by aerosolised substance P in the presence of phosphoramidon. These findings suggest that CRF reduces ovalbumin-induced plasma extravasation in guinea pig airways by inhibiting the release of tachykinins from primary sensory nerves.

Animals↗