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Biomedical subjects

A Cheung

Publications and source records attributed to A Cheung.

At least 19 recordsLinked to original sources
PubMed2007

Could a policy of provision of hip protectors to elderly nursing home residents result in cost savings in acute hip fracture care? The case of Ontario, Canada.

UNLABELLED: Hip fractures are an important problem in nursing homes. Hip protectors are external devices that decrease the risk of hip fracture in elderly nursing home residents. We estimated the overall healthcare cost savings from a hypothetical strategy of provision of hip protectors to elderly nursing home residents in Ontario, Canada. In a recent meta-analysis, we determined that a strategy of provision of hip protectors decreases the risk of hip fracture in nursing home residents. INTRODUCTION: Our objective was to determine whether the provision of hip protectors to all Ontario nursing home residents aged > or =65 years could result in cost savings, stemming from reductions in initial hospitalizations for hip fracture. METHODS: We conducted a cost analysis from a Ministry of Health perspective (one year cycle length). The efficacy of the intervention was estimated from a meta-analysis of randomized controlled trials. RESULTS: A strategy of provision of hip protectors to all 60,775 elderly Ontario nursing home residents could result in an overall mean cost savings of 6.0 million Canadian dollars in one year (95% credibility interval, -26.4 million, 39.7 million), with a probability of cost savings of 0.63 (assuming no additional labor costs). In sensitivity analyses, decreasing hip protector price increased cost savings, whereas additional labor expenditures for application for hip protectors decreased cost savings. CONCLUSION: In conclusion, if hip protectors can be provided to elderly Ontario nursing home residents without additional labor expenditures, there is a reasonable probability that such a strategy may result in healthcare cost savings.

Aged↗
PubMed2005

An in-vitro and in-vivo methodology study of alveolar bone measurement using extra-oral radiographic alignment apparatus, Image Pro-Plus software and a subtraction programme.

OBJECTIVES: (a) To validate a method for acquiring reproducible radiographic images and repeatable measurements of digital images. (b) To investigate the clinical and radiographic changes following periodontal surgery and in a periodontally healthy control group. METHODS: In-vitro study. Sixteen dried human skulls had replicate intra-oral radiographs taken using an extra-oral alignment apparatus under simulated clinical conditions, and measurements were made on the images using Image Pro-Plus analysis software. In-vivo study. Seven subjects, aged 38-63 years with chronic periodontitis, were treated using replaced flap surgery. Nine patients with healthy periodontal tissues were recruited as a control group. Clinical measurements and radiographs were taken pre-surgery and 6 months afterwards, and at the same interval for untreated healthy controls using the alignment apparatus. Radiographs were analysed using Image Pro-Plus and subtraction radiography. RESULTS: Radiographs had a high degree of reliability (ICC 0.98-0.99) for the in-vitro study and intra-operator repeatability of measurements was high (ICC 0.65-0.99) for the in-vivo study. Over this interval there were both significant clinical improvements and in bone gain within infra-bony defects on radiographs. Subtracted images showed that out of 17 surgically treated sites, 13 showed evidence of bone gain, one showed no change, two showed bone loss and one could not be interpreted due to poor alignment. Overall there were no significant clinical or radiographic changes in the control group. CONCLUSIONS: Radiographic images were highly reproducible. Measurements had a high degree of repeatability. The methods used allowed accurate quantitative and qualitative measurement of change in alveolar bone. This technique would allow accurate measurement of any changes in alveolar bone levels in patients with periodontal disease.

Adult↗
PubMed2005

The potential for dental plaque to protect against erosion using an in vivo-in vitro model--a pilot study.

BACKGROUND: Tooth erosion is a problem for professional wine tasters (exogenous erosion from frequent exposure to wine acids) and for people with gastro oesophageal reflux disease (GORD) and bulimia who experience frequent reflux of gastric contents into the mouth (endogenous erosion from mainly HCl). The objective in this study was to determine whether plaque/pellicle could provide teeth with any protection from two common erosive acids, using an in vivo-in vitro technique. METHODS: Tiles of human tooth enamel and root surfaces were prepared from six extracted, unerupted third molar teeth and sterilized. Mandibular stents were prepared for six volunteer subjects and the tiles bonded to the buccal flanges of these stents. They were worn initially for three days to permit a layer of pellicle and plaque to form over the tile surfaces, and for a further 10 days of experimentation. Following cleaning of the plaque/ pellicle layer from the tiles on the right side flange, all the tiles were submerged in either 0.06M HCl or white wine for an accumulated time of 600 and 1500 minutes, respectively. Depths of erosion were determined using light microscopy of sections of the enamel and root tiles. SEM of the lesion surfaces was carried out to investigate the nature of erosive damage and of plaque/pellicle remnants. RESULTS: Retained plaque was found to significantly inhibit dental erosion on enamel, from contact with both HCl and wine, compared with that resulting following its removal. However, it was found to provide no significant protection on root surfaces. SEM analysis of the tile surfaces revealed marked etching of enamel on the cleaned surfaces, and considerable alteration to the appearance of remaining plaque and pellicle on most surfaces. CONCLUSION: Within the limitations of numbers of specimens, dental plaque/pellicle provided a significant level of protection to tooth enamel against dental erosion from simulated gastric acids and from white wine, using an in vivo-in vitro model. It was unable to provide any significant protection to root surfaces from these erosive agents. Possible reasons for this difference are explored.

Calcium Phosphates↗
PubMed2005

Timing of the first endomyocardial biopsy in heart transplantation after induction immunosuppressive therapy--experience from Canadian Heart Transplant Centre.

BACKGROUND: The exact time point at which the first endomyocardial biopsy could be safely performed after the heart transplantation has not been systematically studied. In an attempt to determine this time point in our population, the number and severity of acute rejection episodes in the first eight weeks after the heart transplantation were assessed in 91 patients who underwent the procedure at St Paul's Hospital, Vancouver between September 1996 and December 2002. METHODS AND RESULTS: For the purpose of our analysis, acute rejection was defined as the grade > or =2 according the International Society for Heart and Lung Transplantation (ISHLT). Three hundred and sixty two endomyocardial biopsies were performed in 87 patients surviving to the first biopsy from one to eight weeks after the heart transplantation. In 85 patients who received induction immunosuppressive therapy, 13 episodes of acute rejection were identified. In two patients who did not receive the induction therapy, three episodes of acute rejection occurred. Acute rejection grade ISHLT 3 was found in 2 patients who did not receive induction therapy and in three patients who did. ISHLT grade 4 rejection occurred at weeks 5 and 7 in two patients who received induction therapy. Only one patient who received induction therapy had acute rejection within the first three weeks after the heart transplantation. CONCLUSIONS: Our analysis reveals that the frequency of acute rejection within the first eight weeks after the heart transplantation using induction therapy is low in this cohort, suggesting that the first routine endomyocardial biopsy could be delayed until the week four post-transplant.

Adult↗
PubMed2004

Double-gene ablation of SSTR1 and SSTR5 results in hyperinsulinemia and improved glucose tolerance in mice.

BACKGROUND: Previous studies conducted in our laboratory showed that single-gene ablation of somatostatin receptor (SSTR)1 or 5 results in diabetes in mice. The objective of this study was to determine the effect of double-gene ablation of SSTR1 and SSTR5 on insulin secretion and glucose homeostasis in mice. METHODS: SSTR1/5 -/- mice and wild-type (WT) control mice were generated and their genotype verified via polymerase chain reaction. Insulin secretion and glucose levels in these mice were examined with the use of an intraperitoneal glucose tolerance test (1.2-2.0 g/kg body weight). In vitro glucose-stimulated insulin secretion was studied with the use of the isolated perfused mouse pancreas model and islet culture techniques. Pancreata morphologic alterations were determined, and an immunohistochemistry analysis was performed. RESULTS: In vitro incubation of isolated islets from WT mice with somatostatin peptides resulted in significant reduction in insulin secretion, whereas SSTR1/5 -/- mouse islets had no response to somatostatin peptides confirming SSTR1/5 gene ablation. SSTR1/5 -/- mice also had significant increase of both basal and glucose-stimulated insulin levels in vitro. During the intraperitoneal glucose tolerance test, SSTR1/5 -/- mice had significantly improved glucose tolerance and sustained an increase in late-phase insulin secretion in vivo. Histological analysis demonstrated significant islet hyperplasia in the SSTR 1/5 -/- mouse pancreas. Immunostaining revealed an overall increase of glucagon and pancreatic polypeptide-producing cells in the islets of SSTR1/5 -/- mice. CONCLUSIONS: Double-gene ablation of SSTR1 and SSTR5 in mice resulted in a distinct phenotype with islet cell hyperplasia, hyperinsulinemia, and improved glucose tolerance. This form of diabetes differs from that seen in mice in which only the SSTR1 or SSTR5 gene was ablated. These results demonstrate that SSTR1 and SSTR5 are important regulators of insulin secretion and glucose regulation, and suggest that SSTR1 and SSTR5 are coordinately regulated.

Animals↗
PubMed2003

Communication skill of general practitioners: any room for improvement? How much can it be improved?

OBJECTIVE: To measure any changes in the communication skills of primary care physicians before and after a part-time Diploma course in Family Medicine. SUBJECTS: 79 Hong Kong Chinese doctors (46 of whom were local graduates, with an average of 7 years in general practice). METHODS: Over the 10-month course in 2000-01, participants had 11 2.5-hour lecture/demonstrations in communication skills, 2 sessions of role play practice in groups of 20, self-analysis of a videotaped interview and skills evaluation. A before-after design measured scores in videotaped simulated patient interviews (rated by a research assistant using a structured observation guide, after standardisation by a psychologist) and scores in Objective Structured Clinical Examinations (OSCE) (rated by experienced family physician examiners with standardised checklists). RESULTS: There were wide variations in baseline skills, with scores ranging between 24-78 (out of 100) for video and 18-68 for OSCE, which were related to prior training and inversely associated with years after graduation. Significant improvements occurred in both video (from 53 to 61) and OSCE (from 46 to 56) post-course (P < 0.001). The group in the lowest quartile improved from 36 to 54 for video and from 29 to 48 for OSCE, while those in the second lowest quartile improved from 50 to 61 for video and from 44 to 56 for OSCE (F = 12.2, P < 0.001). Doctors who graduated more than 20 years ago made as much improvement as more recent graduates. CONCLUSIONS: Communication skills can be effectively taught to, and improved among experienced Chinese doctors by a combination of large-class teaching and medium-sized group practice with feedback, and without intensive individual supervision.

Clinical Competence↗
PubMed2003

A controlled study of sleep related disordered breathing in obese children.

BACKGROUND: Unlike the adult sleep related disordered breathing (SDB) patients who are typically obese, the relation between obesity and childhood SDB is not clear. AIMS: To investigate whether obese children are more at risk of obstructive SDB when compared to normal population, and whether this risk is potentiated by the presence of pharyngeal lymphoid tissue. METHODS: Forty six obese children (age 10.8 (SD 2.3) years; BMI 27.4 (SD 5.1)), and 44 sex and age matched normal weight children (age 11.7 (SD 2.1) years; BMI 18 (SD 1.8)) were studied. All children underwent a set of physical examinations (including the upper airways) and sleep studies. RESULTS: The obese children were different from the normal weight children in terms of type (predominantly obstructive), frequency, and severity of respiratory disturbances. Depending on the criteria used, 26% or 32.6% of obese children had SDB; 2.3% of normal controls had OAI > or =1 and 4.5% had RDI > or =5. Presence of SDB was related to presence of tonsils (size >2; range 0-4) (OR 12.67, 95% CI 2.14 to 75.17) and BMI (OR 1.20, 95% CI 1.08 to 1.33). CONCLUSIONS: Results suggest that obese children are at increased risk of obstructive SDB; the presence of any pharyngeal lymphoid tissue enlargement in obese children should therefore be aggressively managed.

Adolescent↗
PubMed2002

A small-molecule inhibitor of skeletal muscle myosin II.

We screened a small-molecule library for inhibitors of rabbit muscle myosin II subfragment 1 (S1) actin-stimulated ATPase activity. The best inhibitor, N-benzyl-p-toluene sulphonamide (BTS), an aryl sulphonamide, inhibited the Ca2+-stimulated S1 ATPase, and reversibly blocked gliding motility. Although BTS does not compete for the nucleotide-binding site of myosin, it weakens myosin's interaction with F-actin. BTS reversibly suppressed force production in skinned skeletal muscle fibres from rabbit and frog skin at micromolar concentrations. BTS suppressed twitch production of intact frog fibres with minimum alteration of Ca2+ metabolism. BTS is remarkably specific, as it was much less effective in suppressing contraction in rat myocardial or rabbit slow-twitch muscle, and did not inhibit platelet myosin II. The isolation of BTS and the recently discovered Eg5 kinesin inhibitor, monastrol, suggests that motor proteins may be potential targets for therapeutic applications.

Adenosine Triphosphatases↗
PubMed2002

No effect of a high-fat diet on promotion of sex hormone-induced prostate and mammary carcinogenesis in the Noble rat model.

Results of international correlation and migrant studies suggest that dietary fat promotes carcinogenesis in hormone-sensitive sites, but this is disputed. In the present study, we used a Noble rat model of sex hormone-induced cancers to examine the effect of a high-fat diet on the incidence and latency of prostate and mammary cancer in male (n 139) and female (n 72) animals respectively. We also measured alpha-tocopherol levels in female breast tissue to determine whether a high intake of polyunsaturated fatty acids depletes antioxidant defence in target tissues, providing a possible potentiating mechanism for carcinogenesis. Results showed a very high incidence of hormone-induced adenocarcinomas of prostate and mammary gland, irrespective of diet. There was no difference in the pattern of carcinogenesis in different prostatic locations, weight of the prostate, or weight gain between male rats on the high-fat diet compared with the control (standard, low-fat) diet. In female rats, the incidence of mammary cancer and the body-weight gain were the same in both dietary groups, and breast alpha-tocopherol was also unaffected by dietary fat intake. Our present results are supportive of recent cohort studies that reported no significant association between intake of fat and the development of human prostate and breast cancer, and do not support a role for dietary fat in promoting sex hormone-induced prostate and mammary carcinogenesis.

Analysis of Variance↗
PubMed2001

Cystic fibrosis pathogens activate Ca2+-dependent mitogen-activated protein kinase signaling pathways in airway epithelial cells.

Much of the pulmonary disease in cystic fibrosis is associated with polymorphonuclear leukocyte-dominated airway inflammation caused by bacterial infection. Respiratory epithelial cells express the polymorphonuclear chemokine interleukin-8 (IL-8) in response to ligation of asialylated glycolipid receptors, which are increased on damaged or regenerating cells and those with cystic fibrosis transmembrane conductance regulator mutations. Because both Pseudomonas aeruginosa and Staphylococcus aureus, the most common pathogens in cystic fibrosis, bind asialylated glycolipid receptors such as asialoGM1, we postulated that diverse bacteria can activate a common epithelial signaling pathway to elicit IL-8 expression. P. aeruginosa PAO1 but not pil mutants and S. aureus RN6390 but not the agr mutant RN6911 stimulated increases in [Ca(2+)](i) in 1HAEo- airway epithelial cells. This response stimulated p38 and ERK1/2 mitogen-activated protein kinase (MAPK) signaling cascades resulting in NF-kappaB activation and IL-8 expression. Ligation of the asialoGM1 receptor or thapsigargin-elicited Ca(2+) release activated this pathway, whereas P. aeruginosa lipopolysaccharide did not. The rapid kinetics of epithelial activation precluded bacterial invasion of the epithelium. Recognition of asialylated glycolipid receptors on airway epithelial cells provides a common pathway for Gram-positive and Gram-negative organisms to initiate an epithelial inflammatory response.

Adhesins, Bacterial↗
PubMed2001

Medical informatics--the state of the art in the Hospital Authority.

Since its inception in 1990, the Hospital Authority (HA) has strongly supported the development and implementation of information systems both to improve the delivery of care and to make better information available to managers. This paper summarizes the progress to date and discusses current and future developments. Following the first two phases of the HA information technology strategy the basic infrastructural elements were laid in place. These included the foundation administrative and financial systems and databases; establishment of a wide area network linking all hospitals and clinics together; laboratory, radiology and pharmacy systems with access to results in the ward. A major push into clinical systems began in 1994 with the clinical management system (CMS), which established a clinical workstation for use in both ward and ambulatory settings. The CMS is now running at all major hospitals, and provides single logon access to almost all the electronically collected clinical data in the HA. The next phase of development is focussed on further support for clinical activities in the CMS. Key elements include the longitudinal electronic patient record (ePR), clinical order entry, generic support for clinical reports, broadening the scope to include allied health and the rehabilitative phase, clinical decision support, an improved clinical documentation framework, sharing of clinical information with other health care providers and a comprehensive data repository for analysis and reporting purposes.

China↗
PubMed2001

Decreased bone mineral density is common after autologous blood or marrow transplantation.

Survivors of autologous blood or marrow transplantation (ABMT) are predisposed to decreased bone mineral density (BMD), but data are lacking on the incidence and risk factors for this condition. Therefore, we measured BMD in 64 of 68 consecutive ABMT survivors (35 men and 29 women) attending the University of Toronto ABMT long-term follow-up clinic. Patients were evaluated a median of 4.2 years (range: 4.9 months-11.4 years) after ABMT. Median age at evaluation was 49.6 years (range: 23.5-68.2 years). At the L1-L4 vertebrae, 17 (26%) patients (eight men and nine women) had osteopenia and one male (2%) had osteoporosis. Mean BMD at L1-L4 did not differ from healthy young adults or age and sex matched controls. At the femoral neck, 30 patients (46%) (18 men and 12 women) had osteopenia and five (8%) (two men and three women) had osteoporosis. Mean BMD at the femoral neck was significantly lower than in healthy young adults and age- and sex-matched controls. By regression analysis, patients with decreased BMD were older than those with normal BMD (P = 0.02). Gender, body mass index, time from BMT to evaluation and presence of hypogonadism were not associated with decreased BMD. Treatment of decreased bone density was instituted and follow-up data were obtained 1 year after treatment in 22 of 39 patients with reduced BMD. Nineteen (86%) patients had stabilization or improvement of their bone density at follow-up. We conclude that, after ABMT, over half of the patients have evidence of osteopenia or osteoporosis. Men and women were equally affected. In our study, only older age at evaluation was predictive for loss of BMD. We recommend the measurement of BMD as an integral component to the follow-up of ABMT patients.

Adult↗
PubMed2001

Diminished virulence of an alpha-toxin mutant of Staphylococcus aureus in experimental brain abscesses.

Staphylococcus aureus is one of the major etiologic agents of brain abscesses in humans, occasionally leading to focal neurological deficits and even death. The objective of the present study was to identify key virulence determinants contributing to the pathogenesis of S. aureus in the brain using a murine brain abscess model. The importance of virulence factor production in disease development was demonstrated by the inability of heat-inactivated S. aureus to induce proinflammatory cytokine or chemokine expression or brain abscess formation in vivo. To directly address the contribution of virulence determinants in brain abscess development, the abilities of S. aureus strains with mutations in the global regulatory loci sarA and agr were examined. An S. aureus sarA agr double mutant exhibited reduced virulence in vivo, as demonstrated by attenuated proinflammatory cytokine and chemokine expression and bacterial replication. Subsequent studies focused on the expression of factors that are altered in the sarA agr double mutant. Evaluation of an alpha-toxin mutant revealed a phenotype similar to that of the sarA agr mutant in vivo, as evidenced by lower bacterial burdens and attenuation of cytokine and chemokine expression in the brain. This suggested that alpha-toxin is a central virulence determinant in brain abscess development. Another virulence mechanism utilized by staphylococci is intracellular survival. Cells recovered from brain abscesses were shown to harbor S. aureus intracellularly, providing a means by which the organism may establish chronic infections in the brain. Together, these data identify alpha-toxin as a key virulence determinant for the survival of S. aureus in the brain.

Animals↗
PubMed2001

Obstructive sleep apnoea in children with adenotonsillar hypertrophy: prospective study.

OBJECTIVE: To determine clinical and baseline polysomnographic data on obstructive sleep apnoea secondary to adenotonsillar hypertrophy in Hong Kong Chinese children. DESIGN: Prospective study. SETTING: University teaching hospital, Hong Kong. PARTICIPANTS: Fifty children (35 boys and 15 girls) suspected to have obstructive sleep apnoea were recruited between January 1999 and December 1999. MAIN OUTCOME MEASURES: Symptoms questionnaire, electrocardiogram, chest radiograph, and full-night polysomnography. RESULTS: All patients had symptoms suggestive of obstructive sleep apnoea. None were found to have clinical evidence of cor pulmonale. Forty-five (90%) of 50 children had obstructive sleep apnoea with a respiratory disturbance index of greater than five. Central and mixed apnoeas were rare. Tonsil size did not correlate with the severity of obstructive sleep apnoea. CONCLUSION: Symptoms and signs suggestive of obstructive sleep apnoea can lead to a high detection rate and confirmation of obstructive sleep apnoea by polysomnography.

Adenoids↗
PubMed2000

GPI 6150 prevents H(2)O(2) cytotoxicity by inhibiting poly(ADP-ribose) polymerase.

GPI 6150 (1,11b-dihydro-[2H]benzopyrano[4,3,2-de]isoquinolin-3-one) is a novel inhibitor of poly(ADP-ribose) polymerase (PARP). It has demonstrated efficacy in rodent models of focal cerebral ischemia, traumatic brain injury, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine damage to dopaminergic neurons, regional myocardial ischemia, streptozotocin-induced diabetes, septic shock, and arthritis. Here we report the structure of GPI 6150, its enzymatic characteristics, and biochemical property in cytoprotection. As a competitive PARP inhibitor (K(i) = 60 nM), GPI 6150 protected the P388D1 cells against hydrogen peroxide cytotoxicity, by preventing PARP activation and the depletion of NAD(+), the substrate for PARP. To address the concerns of potential side effects of PARP inhibition, we tested GPI 6150 and found it had no effect on the repair and expression of a plasmid DNA damaged by N-methyl-N'-nitro-N-nitrosoguanidine. Neither did it affect dehydrogenases with NAD co-enzyme. GPI 6150 was much less potent to inhibit mono-ADP-ribosyltransferase. There was no selectivity for GPI 6150 between PARP isozymes. These attributes render GPI 6150 a useful tool to probe the functions of PARP.

ADP Ribose Transferases↗
PubMed2000

A scintillation proximity assay for poly(ADP-ribose) polymerase.

Poly(ADP-ribose) polymerase (PARP) is an abundant nuclear protein in most of the eukaryotic tissues. When activated by DNA damage, PARP synthesizes poly(ADP-ribose) from NAD. Conventional radioactive PARP enzyme assay requires the separation of the polymer product from the NAD substrate, a rate-limiting step that hampers large-scale chemical library screening to identify novel small-molecule PARP inhibitors. By using biotinylated NAD, we have developed a scintillation proximity assay (SPA) for PARP. We demonstrated that PARP can incorporate the biotinylated ADP-ribose units into the radioactive poly(ADP-ribose) polymer, which can directly bind and excite the streptavidin-conjugated scintillation beads. PARP-SPA can be readily adapted to a 96-well format for automatic high-throughput screening for PARP inhibitors.

Animals↗