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Biomedical subjects

K Chan

Publications and source records attributed to K Chan.

At least 37 records · Page 2Linked to original sources
PubMed2004

Pseudo tamponade soon after cardiac surgery: a report of three cases.

OBJECTIVE: To describe a syndrome suggestive of tamponade but secondary to increased intra-thoracic pressure due to undetected dyssynchronous expiratory efforts in mechanically ventilated patients soon after cardiac surgery. METHODS: A retrospective chart review of three patients immediately after cardiac surgery. RESULTS: All patients developed the tetrad of decreased blood pressure, increased central venous pressure, decreased cardiac index and decreased urine output soon after cardiac surgery without other obvious reasons. In all patients, tamponade was suspected. In all cases, physical examination found no marked evidence of patient-ventilator dyssynchrony but evidence of abdominal muscle tensing and intermittent expiratory efforts not in synchrony with the ventilator cycle. In all patients, sedation and muscle relaxation led to a decrease in central venous pressure, improved blood pressure and improved cardiac index and urine output with full resolution of the syndrome. All patients were successfully extubated within 24 hours of surgery. CONCLUSIONS: In some postoperative cardiac surgery patients expiratory efforts which are not in synchrony with mechanical ventilation and not immediately obvious to clinicians or intensive care unit nurses can simulate tamponade. Greater awareness of this syndrome may decrease the chance of diagnostic error.

Journal Article↗
PubMed2003

Some aspects of toxic contaminants in herbal medicines.

A World Health Organisation survey indicated that about 70-80% of the world populations rely on non-conventional medicine mainly of herbal sources in their primary healthcare. In recent years, we have witnessed the increasing growth in popularity of over-the-counter (OTC) health foods, nutraceuticals, and medicinal products from plants or other natural sources in developed countries. This indirectly indicates that the public is not satisfied with their orthodox medical (OM) treatment. Such increase in popularity has also brought concerns and fears over the professionalism of practitioners, and quality, efficacy and safety of their treatment methods and products from herbal and natural sources available in the market. Over the past decade several news-catching episodes in developed communities indicated adverse effects, sometimes life threatening, allegedly arisen consequential to taking of OTC herbal products or traditional medicines from various ethnic groups. These OTC products may be contaminated with excessive or banned pesticides, microbial contaminants, heavy metals, chemical toxins, and for adulterated with orthodox drugs. Excessive or banned pesticides, heavy metals and microbial contaminants may be related to the source of these herbal materials, if they are grown under contaminated environment or during collection of these plant materials. Chemical toxins may come from unfavourable or wrong storage conditions or chemical treatment due to storage. The presence of orthodox drugs can be related to unprofessional practice of manufacturers. Some of these environment related factors can be controlled by implementing standard operating procedures (SOP) leading to Good Agricultural Practice (GAP), Good Laboratory Practice (GLP), Good Supply Practice (GSP) and Good Manufacturing Practice (GMP) for producing these medicinal products from herbal or natural sources. The public's belief that herbal and natural products are safer than synthetic medicines can only be ascertained by imposing regulatory standards on these products that should be manufactured using these Good Practices. Using Chinese medicines, as examples, this paper illustrate how advances in chemical and biomedical analysis would help to detect intentional and unintentional toxic contaminants in herbal substances. The paper also summarises how modernization and progress are being carried out to get the best out of Chinese medicines for public healthcare.

Consumer Product Safety↗
PubMed2003

Unintentional residential child injury surveillance in Hong Kong.

OBJECTIVES: To provide an overall pattern of morbidity in unintentional residential childhood injuries (URCI) in Hong Kong. METHODOLOGY: A cross-sectional telephone survey of caregivers of children aged under 16-years and adolescents suffering from URCI and admitted to three selected local Accident and Emergency Departments. RESULTS: Falls, cuts and scalds were the most common external causes of URCI observed, while boys predominated in the sample population. Most of the observed URCI were of moderate to mild severity. Children of new immigrant mothers were more likely to receive first aid immediately after the incidents. Parents were aware of potentially injurious behaviour and intervened on occasion, but most resorted to verbal warnings only. CONCLUSIONS: Prevalence of falls among observed URCI offers evidence in support of the hypothesis that the high population density in Hong Kong plays an integral role in understanding mechanisms of morbidity. Parents show concern about URCI but often lack substantial action that modifies injury risk. Considering the local injury differentials, an active prevention effort such as behavioural intervention and education for parents may be useful.

Accident Prevention↗
PubMed2003

Malignant mesothelioma: experience at the Singapore General Hospital.

INTRODUCTION: Malignant mesothelioma is a rare occupational disease in Singapore. There have been few reports of this condition in Singapore. We aim to describe the clinical characteristics, management and outcomes in a case series of 16 patients diagnosed in a teaching hospital in Singapore. MATERIALS AND METHODS: A chart review of all cases of malignant mesothelioma diagnosed in our institution during the period 1996 to 2001 was conducted, with particular attention to the occupational history. RESULTS: There were 16 patients (15 male patients) with a median age of 61.5 (range, 46 to 78) years. Thirteen patients had malignant pleural mesothelioma (MPM) and 3 patients had mesothelioma of the periotoneum. Eleven of the patients with MPM (84.6%) presented with a pleural effusion and only 2 patients (15.4%) had chest pain. Initial pleural fluid cytology and closed pleural biopsies were negative in all patients who presented with a pleural effusion. Thoracoscopy confirmed the histologic diagnosis and allowed simultaneous talc pleurodesis in 9 patients. All patients had documented asbestos exposure, of which 14 (87.5%) were confirmed to be occupationally related. The median time from first exposure to symptoms was 33.5 (range, 16 to 53) years. The median survival was 6 months. Most of the patients (75%) received best supportive care alone. CONCLUSIONS: In our experience, malignant mesothelioma is an aggressive disease with a poor prognosis. It is strongly associated with asbestos exposure. Thoracoscopy is an invaluable diagnostic modality in the evaluation of a patient with occupational asbestos exposure and an undiagnosed pleural effusion.

Aged↗
PubMed2002

A demographic and health profile of gay and bisexual men in a large Canadian urban setting.

The purpose of this study was to provide both a population estimate and a socio-economic and health profile of gay and bisexual men living with HIV/AIDS in a large Canadian urban centre. A random telephone survey was used to determine the number of men in the study area over the age of 20 identifying as gay or bisexual and to characterize their health and socio-economic status. Out of a total of 1,176 completed interviews, 300 males described themselves as gay or bisexual. Projecting this figure on recent census data we estimated the number of men identifying as gay or bisexual in this region of downtown Vancouver, BC, at 5,100. Among these men we found an HIV prevalence rate of 16%, with those who reported a positive serostatus being less likely to be employed full time and more likely to earn less than $20,000 per year. In terms of clinical characteristics, HIV-positive men had a median CD4 cell count of 397 cells/mm(3) and a median viral load of less than 500 copies/ml. Eighty-three per cent of the HIV-positive respondents were on antiretroviral therapy and the median number of drugs taken by these men was three. In summary, random surveys of populations affected by this epidemic are important for policy makers, clinicians and persons caring for those with HIV/AIDS as they paint a clearer picture of who is being affected and help to identify areas where increased services are needed.

Adult↗
PubMed2002

Naphthalene-induced respiratory tract toxicity: metabolic mechanisms of toxicity.

The lung, which is in intimate contact with the external environment, is exposed to a number of toxicants both by virtue of its large surface area and because it receives 100% of the cardiac output. Lung diseases are a major disease entity in the U.S. population ranking third in terms of morbidity and mortality. Despite the importance of these diseases, key issues remain to be resolved regarding the interactions of chemicals with lung tissue and the factors that are critical determinants of chemical-induced lung injury. The importance of cytochrome P450 monooxygenase dependent metabolism in chemical-induced lung injury in animal models was established over 25 years ago with the furan, 4-ipomeanol. Since then, the significance of biotransformation and the reasons for the high degree of pulmonary selectivity for a myriad of different chemicals has been well documented, mainly in rodent models. However, with many of these chemicals there are substantial differences in the susceptibility of rats vs. mice. Even within the same species, varied levels of the respiratory tract respond differently. Thus, key pieces of data are still missing when evaluating the applicability of data generated in rodents to primates, and as a result of this, there are substantial uncertainties within the regulatory community with regards to assessing the risks to humans for exposure to some of these chemicals. For example, all of the available data suggest that the levels of cytochrome P450 monooxygenases in rodent lungs are 10-100 times greater than those measured in the lungs of nonhuman primates or in man. At first glance, this suggests that a significant margin of safety exists when evaluating the applicability of rodent studies in the human, but the issues are more complex. The intent of this review is to outline some of the work conducted on the site and species selective toxicity and metabolism of the volatile lung toxic aromatic hydrocarbon, naphthalene. We argue that a complete understanding of the cellular and biochemical mechanisms by which this and other lung toxic compounds generate their effects in rodent models with subsequent measurement of these cellular and biochemical events in primate and human tissues in vitro will provide a far better basis for judging whether the results of studies done in rodent models are applicable to humans.

Animals↗
PubMed2001

ZD1839 (Iressa), a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, potently inhibits the growth of EGFR-positive cancer cell lines with or without erbB2 overexpression.

Overexpression of the growth factor receptors EGFR and erbB2 occurs frequently in several human cancers and is associated with aggressive tumour behaviour and poor patient prognosis. We have investigated the effects of ZD1839 (Iressa), a novel EGFR tyrosine kinase inhibitor, on the growth, in vitro and in vivo, of human cancer cell lines expressing various levels of EGFR and erbB2. Proliferation of EGFR-overexpressing A431 and MDA-MB-231 cells in vitro was potently inhibited (50%-70%) by ZD1839 with half-maximally effective doses in the low nanomolar range. In parallel, ZD1839 blocked autophosphorylation of EGFR and prevented activation of PLC-gamma 1, ERK MAP kinases and PKB/Akt by EGF. It also inhibited proliferation in EGFR(+) cancer cell lines overexpressing erbB2 (SKBr3, SKOV3, BT474) by between 20% and 80%, effects which correlated with inhibition of EGF-dependent erbB2 phosphorylation and activation of ERK MAP kinase and PKB/Akt in SKOV3 cells. Oral administration of ZD1839 inhibited the growth of MDA-MB-231 and SKOV3 tumours, established as xenografts in athymic mice, by 71% and 32%, respectively. Growth inhibition coincided with reduced proliferation but no change in apoptotic index. Collectively, these results show that ZD1839, at the doses studied, is a potent inhibitor of proliferation not only in cells overexpressing EGFR but also in EGFR(+) cells that overexpress erbB2.

Cell Division↗
PubMed2001

Longitudinal patterns of sexual behavior and condom use in a cohort of HIV-negative gay and bisexual men in Vancouver, British Columbia, Canada, 1995-2000.

OBJECTIVE: To characterize longitudinal patterns of sexual behavior in a cohort of young gay and bisexual men and determine their reasons for not using condoms. METHODS: Prospective data from a cohort of young gay and bisexual men aged 18 to 30 years were studied. Study participants had completed a baseline questionnaire and HIV test between May 1995 and April 1996 and four annual follow-up questionnaires. RESULTS: A total of 130 HIV-negative Vanguard participants met the eligibility criteria for this analysis. The median age at baseline was 26 years (range, 24-28). Most were white (79%), had completed high school (85%), were currently employed (82%), lived in stable housing (95%), and reported annual incomes of > or =$10,000 (82%). (All dollar amounts are given in Canadian dollars.) Consistently over the 5-year study period, > 70% of study subjects reported having > or =1 regular male sexual partners in the previous year. During each of the five successive 1-year periods, between 34% and 40% of respondents reported having had unprotected receptive anal intercourse with regular partners. Slightly fewer individuals (between 29%-39%) reported having had unprotected insertive anal intercourse with regular partners. Between 13% and 25% of participants reported having had insertive unprotected anal intercourse with casual sexual partners; and between 9% and 18% reported having had unprotected receptive anal intercourse with casual sexual partners. Reasons for engaging in unprotected anal intercourse varied depending on type of sexual partnership. CONCLUSION: High-risk sexual behaviors remained fairly consistent over a 5-year period in this study. This suggests that it is critically important to understand the motivations for unprotected sex when designing and implementing programs aimed at reducing HIV risk among young gay and bisexual men.

Adolescent↗
PubMed2001

Constitutive expression of ErbB-2 in gallbladder epithelium results in development of adenocarcinoma.

Overexpression of ErbB-2 in the basal layer of biliary tract epithelium led to the development of gallbladder adenocarcinoma in 100% of transgenic mice by 3 months of age. In addition, tumors developed in other parts of the biliary tree (e.g., cholangiocarcinoma). Adenocarcinoma of the gallbladder appeared to arise via a stepwise process involving hyperplasia, adenoma formation, and then adenocarcinoma formation. Increased ErbB-2/epidermal growth factor receptor heterodimer formation, activation of mitogen-activated protein kinase, and up-regulation of cyclooxygenase-2 levels (mRNA and protein) were observed in gallbladder epithelium of these mice. These mice represent a unique new animal model for studying biliary tract carcinogenesis.

Adenocarcinoma↗
PubMed2001

Risk factors associated with HIV infection among young gay and bisexual men in Canada.

OBJECTIVE: To assess risk factors associated with HIV prevalence and incidence among gay and bisexual men in two prospective Canadian cohorts. METHODS: The Vanguard Project and the Omega Cohort are prospective cohort studies of gay and bisexual men ongoing in Vancouver and Montreal, respectively. For this analysis, baseline sociodemographic characteristics, sexual behavior, and substance use data from these two cohorts were combined. Assessment of risk factors for HIV seroprevalence and seroconversion were carried out using univariate and multivariate analysis. RESULTS: This analysis was based on 1373 gay and bisexual men aged 16 to 30 years. Men who were HIV-seropositive at baseline (n = 48) were more likely to report living in unstable housing, to have had less than a high school education, and to have been unemployed than those who were HIV-negative (n = 1325). HIV-positive men were also more likely to report having engaged in sexual risk behavior, including having had consensual sex at a younger age, having had at least 6 partners during the previous year, ever having been involved in the sex trade, and having engaged in unprotected receptive anal intercourse. With respect to substance use, HIV-positive men were more likely to report the use of crack, cocaine, heroin, and marijuana and to use injection drugs. Similarly, men who seroconverted during the course of the studies (n = 26) were more likely to report having less than a high school education and having lived in unstable housing at baseline. Compared with HIV-negative men, men who seroconverted were more likely to report ever having been involved in the sex trade and engaging in unprotected receptive anal intercourse. Reports of cocaine use and injection drug use were also significantly higher for men who seroconverted compared with HIV-negative men. CONCLUSIONS: Our data indicate that HIV-positive gay and bisexual men are more likely to be living in unstable conditions and to report more risky sexual and substance use behaviors than HIV-negative men.

Adolescent↗
PubMed2001

Increasing incidence of HIV infections among young gay and bisexual men in Vancouver.

Since the beginning of the HIV epidemic in north America, the majority of HIV infections have occurred among men who engage in sexual relations with other men. As the HIV epidemic enters its third decade, gay and bisexual men continue to have among the highest rates of HIV infection. Previous studies have highlighted the decline in the incidence of HIV and risk behaviour among gay and bisexual men. However, several studies have suggested that young gay and bisexual men continue to engage in unprotected sexual behaviours and are at continued risk of HIV infection. Recent reports in the media and research literature have indicated an increase in the incidence of HIV among gay and bisexual individuals in many of the world's major cities. The purpose of this study was to determine trends in HIV incidence using data from a prospective cohort of young gay and bisexual men.

Adolescent↗
PubMed2001

An important function of Nrf2 in combating oxidative stress: detoxification of acetaminophen.

Nrf2, a member of the "cap 'n collar" group of transcription factors, is important for protecting cells against oxidative damage. We investigated its role in the detoxification of acetaminophen [N-acetyl-p-aminophenol (APAP)]-induced hepatotoxicity. When Nrf2 knockout (Nrf2(-/-)) and wild-type mice were given APAP by i.p. injection, the Nrf2(-/-) mice were highly susceptible to APAP treatment. With doses of APAP that were tolerated by wild-type mice, the Nrf2(-/-) mice died of liver failure. When hepatic glutathione was depleted after a dose of 400 mg/kg of APAP, the wild-type mice were able to compensate and regain the normal glutathione level. In contrast, the glutathione level in the Nrf2(-/-) mice was not compensated and remained low. This was because of the decrease in the gene expression of gcs(H) and gcs(L) as well as gss in the livers of the Nrf2(-/-) mice. In addition, the expression of ugt1a6 and gstpi that detoxify APAP by conjugation was also decreased. This increased susceptibility of the Nrf2(-/-) mice to APAP, because of an impaired capacity to replenish their glutathione stores, compounded with a decreased detoxification capability, highlights the importance of Nrf2 in the regulation of glutathione synthesis and cellular detoxification processes.

Acetaminophen↗
PubMed2001

HIV protease and reverse transcriptase variation and therapy outcome in antiretroviral-naive individuals from a large North American cohort.

OBJECTIVE: To assess the effect of baseline HIV reverse transcriptase (RT) and protease sequence variation on virologic outcomes in a large cohort of antiretroviral-naive patients in British Columbia, Canada. METHODS: Population sequencing of RT and protease was performed on baseline viral RNA of all antiretroviral-naive patients first seeking treatment in British Columbia between June 1997 and August 1998 (n = 479). Relative risks of virological failure associated with genotypic differences from a 'standard' HIV strain (HXB2) were assessed for up to 18 months. RESULTS: The prevalence of key baseline mutations known to confer resistance to RT and protease inhibitors (PI) was 3.4 and 3.8%, respectively. No statistically significant impact on virologic outcomes could be established for these patients. However, the data suggest that some individuals (harboring a M184V mutation in RT or a V82I in protease) may have benefited from pre-therapy resistance tests. 'Secondary' mutations in the protease associated with resistance (e.g. codons 10, 36 or 63) were common, but the presence of these secondary mutations, either alone or in combination, did not appear to result in early loss of therapeutic virological suppression. Preliminary analyses suggest that an amino acid change at codon 35 in the protease may be associated with early treatment failure. CONCLUSIONS: The results suggest that routine genotyping of naive patients about to start antiretroviral therapy would be of benefit to a relatively small proportion of the population. Secondary mutations associated with resistance to PI alone were not found to affect virologic outcomes significantly.

Anti-HIV Agents↗
PubMed2001

The roles of MHC class II, CD40, and B7 costimulation in CTL induction by plasmid DNA.

DNA-based vaccines generate potent CTL responses. The mechanism of T cell stimulation has been attributed to plasmid-transfected dendritic cells. These cells have also been shown to express plasmid-encoded proteins and to become activated by surface marker up-regulation. However, the increased surface expression of CD40 and B7 on these dendritic cells is insufficient to overcome the need for MHC class II-restricted CD4(+) T cell help in the priming of a CTL response. In this study, MHC class II(-/-) mice were unable to generate a CTL response following DNA immunization. This deficit in CTL stimulation by MHC class II-deficient mice was only modestly restored with CD40-activating Ab, suggesting that there were other elements provided by MHC class II-restricted T cell help for CTL induction. CTL activity was also augmented by coinjection with a vector encoding the costimulatory ligand B7.1, but not B7.2. These data indicate that dendritic cells in plasmid DNA-injected mice require conditioning signals from MHC class II-restricted T cells that are both CD40 dependent and independent and that there are different roles for costimulatory molecules that may be involved in inducing optimal CTL activity.

Adjuvants, Immunologic↗
PubMed2001

Synthesis and biological activity of novel potent endothelin-converting enzyme-1 inhibitors.

Through directed screening of metalloprotease inhibitors, CGS 30084 (1) has been identified as a potent endothelin-converting enzyme-1 (ECE-1) inhibitor in vitro (IC50 = 77 nM). Herein we report the syntheses and biological activities of analogues derived from this lead, based on modifications of the biphenyl moiety. Compound 10, the thioacetate methyl ester prodrug derivative of compound 6m, was found to be an orally active and potent inhibitor of ECE-1 activity in rats.

Alanine↗