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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
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↗
PubMed1995

Site-specific N-terminal auto-degradation of human serum albumin.

Human serum albumin prepared by blood fractionation for clinical purposes was found to degrade when stored at or above 30 degree C. Mass spectrometry and N-terminal sequencing of the protein identified degradation corresponding to the loss of the first two residues, aspartic acid and alanine. The reaction was shown to be dependent upon temperature and the N-terminal alpha-amino group. In addition, comparison with serum albumins derived from other species showed that the instability of the N-terminus was specific to the human albumin sequence. An intact aspartyl-alanyl dipeptide, purified from degraded albumin solutions, differed substantially from a synthetic dipeptide on amino acid analysis, N-terminal sequencing and NMR. It is suggested that the released dipeptide may be cyclic, implying a novel cleavage mechanism.

Amino Acid Sequence↗
PubMed1995

Anterior lung herniation: another aspect of the seatbelt syndrome.

Shoulder harnesses can be a source of thoracic injury in motor vehicle crashes. Sternal and rib fractures are most commonly reported. We present a case of a traumatic anterior lung herniation secondary to shoulder harness trauma in a motor vehicle crash victim with multiple injuries. A brief review of lung hernias is provided as well as a brief discussion of the thoracic manifestations of the seatbelt syndrome.

Accidents, Traffic↗
PubMed1995

Neutrophil elastase-alpha 1-antitrypsin in middle ear fluid in chronic otitis media with effusion.

Neutrophil elastase-alpha 1-antitrypsin was quantified in samples taken from middle ear effusions collected at operation from 17 children attending for elective myringotomy and grommet insertion. At the time of surgery the effusion was classified as serous or mucoid. Children with a recent history of infection or antimicrobial therapy were excluded. The quantification of immunoreactive neutrophil elastase was by means of enzyme-linked immunosorbant assay (ELISA). The mean value of neutrophil elastase-alpha 1-antitrypsin was 50.6 +/- 38.3 (SD) micrograms/ml in mucoid effusions, which was significantly higher (P < 0.05) than that in serous effusions (5.3 +/- 4.8 micrograms/ml). These results indicate that a mucoid effusion may reflect a more severe inflammatory response and that persistence of neutrophil activity in the middle ear mucosa may contribute to the persistence of at least one group of middle ear effusions.

Child↗
PubMed1995

Inhibition of bronchoconstriction by pituitary adenylate cyclase activating polypeptide (PACAP 1-27) in guinea-pigs in vivo.

1. We studied the inhibitory effect of pituitary adenylate cyclase activating polypeptide (PACAP 1-27) on the increase in total pulmonary resistance (RL) caused either by allergen or histamine in anaesthetized, ventilated guinea-pigs. 2. PACAP 1-27 given via i.v. infusion (0.045-4.5 nmol kg-1 min-1) dose-dependently reduced the increase in RL caused by inhaled ovalbumin and histamine. At the highest dose, PACAP 1-27 prevented the increase in RL caused by ovalbumin and histamine completely. Infusion of PACAP 1-27 and the beta 2-adrenoceptor agonist, salbutamol (0.045-4.5 nmol kg-1 min-1) inhibited the increase in RL similarly, but salbutamol increased the heart rate more than PACAP 1-27. 3. PACAP 1-27 and salbutamol given via inhaled aerosol (0.1 mM, 20 breaths) significantly reduced the increase in RL caused by histamine infused i.v., whereas aerosolised sterile saline did not. Both PACAP 1-27 and salbutamol caused bronchodilator effects within 1 min of drug inhalation and these effects remained throughout the 20 min of study. 4. Because PACAP 1-27 produced significant bronchodilatation and rapid onset of sustained action in vivo and without pronounced cardiovascular side effects, we conclude that this peptide may have therapeutic potential as a bronchodilator.

Adenylyl Cyclases↗
PubMed1995

Increase in interleukin-8 and soluble intercellular adhesion molecule-1 in bronchoalveolar lavage fluid from premature infants who develop chronic lung disease.

Interleukin-8 (IL-8), soluble intercellular adhesion molecule-1 (sICAM), elastase and neutrophils were assessed in bronchoalveolar lavage fluid from nine infants who developed chronic lung disease (CLD) after respiratory distress syndrome (RDS), seven who had recovered from RDS, and in four control infants. IL-8, sICAM, elastase and neutrophils in bronchoalveolar lavage fluid were increased in the CLD group, the differences being most pronounced at 10 days of age. When babies with and without CLD were compared at 10 days of age, bronchoalveolar lavage fluid from the babies with CLD had significantly increased IL-8 (114.0 vs 12.7 ng/ml), sICAM (19.0 vs 1.1 micrograms/ml), elastase (6.9 vs 0.9 micrograms/ml) and neutrophils (1.9 vs 0.4 x 10(9)/l). In serum the increased concentration of IL-8 observed at birth in the CLD (247 pg/ml) and RDS (192 pg/ml) groups decreased over three weeks to the concentrations observed in the controls (< 70 pg/ml). Persistent inflammation could be a major contributory factor in the development of CLD.

Bronchoalveolar Lavage Fluid↗