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Biomedical subjects

R K Chan

Publications and source records attributed to R K Chan.

At least 19 recordsLinked to original sources
PubMed2003

Ischaemia-reperfusion is an event triggered by immune complexes and complement.

BACKGROUND: Reperfusion injury is a common clinical problem that lacks effective therapy. Two decades of research implicating oxygen free radicals and neutrophils has not led to a single successful clinical trial. METHODS: The aim was to review new clinical and preclinical data pertaining to the alleviation of reperfusion injury. A review of the literature was undertaken by searching the MEDLINE database for the period 1966-2003 without language restrictions. RESULTS AND CONCLUSION: Evidence now points to complement and immune complexes as critical players in mediating reperfusion injury. Ischaemia is postulated to induce a phenotypical cellular change through the surface expression of a neoantigen. Preformed circulating natural IgM antibodies are then trapped and complement is activated. Final events leading to reperfusion injury include formation of the membrane attack complex and mast cell degranulation.

Antigen-Antibody Complex↗
PubMed2000

Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse.

Two G protein-coupled receptors have been identified that bind corticotropin-releasing factor (CRF) and urocortin (UCN) with high affinity. Hybridization histochemical methods were used to shed light on controversies concerning their localization in rat brain, and to provide normative distributional data in mouse, the standard model for genetic manipulation in mammals. The distribution of CRF-R1 mRNA in mouse was found to be fundamentally similar to that in rat, with expression predominating in the cerebral cortex, sensory relay nuclei, and in the cerebellum and its major afferents. Pronounced species differences in distribution were few, although more subtle variations in the relative strength of R1 expression were seen in several forebrain regions. CRF-R2 mRNA displayed comparable expression in rat and mouse brain, distinct from, and more restricted than that of CRF-R1. Major neuronal sites of CRF-R2 expression included aspects of the olfactory bulb, lateral septal nucleus, bed nucleus of the stria terminalis, ventromedial hypothalamic nucleus, medial and posterior cortical nuclei of the amygdala, ventral hippocampus, mesencephalic raphe nuclei, and novel localizations in the nucleus of the solitary tract and area postrema. Several sites of expression in the limbic forebrain were found to overlap partially with ones of androgen receptor expression. In pituitary, rat and mouse displayed CRF-R1 mRNA signal continuously over the intermediate lobe and over a subset of cells in the anterior lobe, whereas CRF-R2 transcripts were expressed mainly in the posterior lobe. The distinctive expression pattern of CRF-R2 mRNA identifies additional putative central sites of action for CRF and/or UCN. Constitutive expression of CRF-R2 mRNA in the nucleus of the solitary tract, and stress-inducible expression of CRF-R1 transcripts in the paraventricular nucleus may provide a basis for understanding documented effects of CRF-related peptides at a loci shown previously to lack a capacity for CRF-R expression or CRF binding. Other such "mismatches" remain to be reconciled.

Animals↗
PubMed2000

Fine structure and plasticity of barosensitive neurons in the nucleus of solitary tract.

Intravenous phenylephrine (PE) activates neurons in the nucleus of the solitary tract (NTS) whose distribution conforms to those of central projections of the carotid sinus and aortic depressor nerves. This was exploited to permit fine structural characterization of cells presumed to compose the first station in the processing of arterial baroreceptor input, and their responses to stimulation. Rats were perfused at varying intervals after PE injection, and sections through the baroreceptor afferent zone of the NTS prepared for preembedding immunolocalization of Fos-immunoreactivity. Labeled neurons composed a continuous strip extending from the dorsal part of the commissural NTS (NTScom) to the dorsal subnucleus at the level of the area postrema (NTSap). PE-sensitive neurons in these regions were medium-sized, round to ovoid in shape, with scant cytoplasm and an unremarkable complement of organelles. Distinctive features included extensively invaginated nuclei and well-developed Golgi apparati; Fos-ir cells in the NTSap were distinguished from those in NTScom by virtue of better-developed rough endoplasmic reticulum and Golgi, and less convoluted nuclei. Proximal synaptic input to PE-sensitive neurons was sparse and was provided by terminals containing predominantly small, clear synaptic vesicles that formed mainly symmetric junctions with somata and primary dendrites. Prolonged stimulation was accompanied by accentuation of nuclear invaginations, marked accumulation of heterochromatin at their apices, and evidence of enhanced Golgi activity (vesicular budding). These may represent adaptations to facilitate changes in gene expression, to maintain neurotransmitter availability, or both, in the face of a persistent hypertensive challenge.

Animals↗
PubMed2000

The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.

BACKGROUND: The causes of stroke in patients with asymptomatic carotid-artery stenosis have not been carefully studied. Information about causes might influence decisions about the use of carotid endarterectomy in such patients. METHODS: We studied patients with unilateral symptomatic carotid-artery stenosis and asymptomatic contralateral stenosis from 1988 to 1997. The causes, severity, risk, and predictors of stroke in the territory of the asymptomatic artery were examined and quantified. RESULTS: The risk of stroke at five years after study entry in a total of 1820 patients increased with the severity of stenosis. Among 1604 patients with stenosis of less than 60 percent of the luminal diameter, the risk of a first stroke was 8.0 percent (1.6 percent annually), as compared with 16.2 percent (3.2 percent annually) among 216 patients with 60 to 99 percent stenosis. In the group with 60 to 99 percent stenosis, the five-year risk of stroke in the territory of a large artery was 9.9 percent, that of lacunar stroke was 6.0 percent, and that of cardioembolic stroke 2.1 percent. Some patients had more than one stroke of more than one cause. In the territory of an asymptomatic occluded artery (as was identified in 86 patients), the annualized risk of stroke was 1.9 percent. Strokes with different causes had different risk factors. The risk factors for large-artery stroke were silent brain infarction, a history of diabetes, and a higher degree of stenosis; for cardioembolic stroke, a history of myocardial infarction or angina and hypertension; for lacunar stroke, age of 75 years or older, hypertension, diabetes, and a higher degree of stenosis. CONCLUSIONS: The risk of stroke among patients with asymptomatic carotid-artery stenosis is relatively low. Forty-five percent of strokes in patients with asymptomatic stenosis of 60 to 99 percent are attributable to lacunes or cardioembolism. These observations have implications for the use of endarterectomy in asymptomatic patients. Without analysis of the risk of stroke according to cause, the absolute benefit associated with endarterectomy may be overestimated.

Aged↗
PubMed2000

Paradoxical activational effects of a corticotropin-releasing factor-binding protein "ligand inhibitor" in rat brain.

The corticotropin-releasing factor-binding protein is distinct from known corticotropin-releasing factor receptors, but can bind the peptide and neutralize its biological actions. Recent interest has centered about the therapeutic potential of "ligand inhibitors" of binding protein action, synthetic corticotropin-releasing factor fragments which are inactive at corticotropin-releasing factor receptors, but can displace the peptide from the binding protein, thereby increasing levels of free corticotropin-releasing factor. To identify sites of action of such ligands, the distribution of Fos expression seen following intracerebroventricular administration of rat/human corticotropin-releasing factor(6-33) (5-50 microg) was charted in relation to corticotropin-releasing factor-binding protein and receptor expression. It was expected that Fos induction would mimic aspects of the distribution of the two known corticotropin-releasing factor receptors, but the far greater correspondence was seen with that of the binding protein itself. This included neurons in the isocortex, the olfactory system, amygdala and a number of discrete brainstem cell groups; many Fos-immunoreactive neurons in each were found to co-express corticotropin-releasing factor-binding protein messenger RNA. Subsets of activated neurons co-expressed Type 1 corticotropin-releasing factor receptor messenger RNA, though these were largely limited to cell groups that also express the corticotropin-releasing factor-binding protein, and where binding protein immunoreactivity and Type 1 receptor transcripts were found to co-exist. Responsive neurons displaying Type 2 corticotropin-releasing factor receptor message were seen reliably only in the lateral septal nucleus. These findings support only a limited capacity of the ligand inhibitor to activate neurons bearing corticotropin-releasing factor receptors. The more pervasive activation seen among neurons that express the corticotropin-releasing factor-binding protein may be indicative of an unexpected role for this protein in signaling by corticotropin-releasing factor-related peptides.

Animals↗
PubMed2000

Effects of selective sinoaortic denervations on phenylephrine-induced activational responses in the nucleus of the solitary tract.

Intravenous administration of phenylephrine provokes a pattern of cellular activation in the nucleus of the solitary tract that resembles the central distributions of primary baroreceptor afferents supplied by the carotid sinus and aortic depressor nerves. Transganglionic transport and denervation methods were used in an experimental setting to test the dependence of phenylephrine-induced Fos immunoreactivity on the integrity of buffer nerve afferents, and to identify the subregions of the nucleus of the solitary tract supplied by each. Cholera toxin B-horseradish peroxidase injections into either or both nerves revealed terminal labeling concentrated in, but not restricted to, the dorsal commissural part of the nucleus of the solitary tract at the level of the apex of calamus scriptorius, and extending into the dorsal subnucleus at the level of the area postrema. Preferential ramifications of carotid sinus and aortic depressor nerve afferents at the levels of the commissural part of the nucleus and the area postrema, respectively, were reflected in the extent to which labeled fibers comingled with neurons exhibiting phenylephrine-induced Fos in dual labeling experiments. Complete sinoaortic denervation reduced by 90% the number of neurons exhibiting drug-induced Fos expression. Selective carotid and aortic sinus denervations effected partial reductions manifest preferentially in the caudal and rostral foci of the distribution, respectively. Reduced activational responses at the level of the area postrema of aortic sinus-denervated rats were accompanied by a reduction in cellular nicotinamide adenine dinucleotide phosphate-diaphorase activity in this region. Animals killed 30 days after complete sinoaortic denervation displayed no evidence of recovery of phenylephrine-induced Fos, while the strength and distribution of the response in rats that received selective carotid sinus denervation were indistinguishable from those seen in controls. These findings (i) support the dependence of phenylephrine-induced Fos expression on the integrity of carotid sinus and aortic depressor nerve afferents, (ii) provide anatomical and functional evidence that the two buffer nerves distribute differentially within the nucleus of the solitary tract, and (iii) implicate central reorganization as a likely basis for functional recovery of baroreflex mechanisms following partial sinoaortic denervation.

Animals↗
PubMed2000

Factors associated with condom use for oral sex among female brothel-based sex workers in Singapore.

BACKGROUND AND OBJECTIVE: The prevalence of oral sex increased from 27.1% in 1992 to 81.1% in 1997, with a concomitant increase in pharyngeal gonorrhea, among female sex workers in Singapore. The extent of condom use for oral sex among them is unknown. GOAL: To determine the prevalence of and factors associated with consistent condom use during oral sex. STUDY DESIGN: A cross-sectional study of 225 women randomly selected from the surveillance scheme register of female brothel-based sex workers with a history of oral sex documented in their medical records. RESULTS: Slightly more than half (56.9%) consistently used condoms for oral sex compared to 97% for vaginal sex. Condom use was significantly higher among middle than high class sex workers (adjusted rate ratio: 1.52, 95% CI: 1.01-2.29) and those with negotiation skills (adjusted rate ratio: 1.95, 95% CI: 1.32-2.07). CONCLUSION: Sex workers should be taught skills to negotiate condom use for oral sex.

Adult↗
PubMed2000

A prospective study on condom slippage and breakage among female brothel-based sex workers in Singapore.

BACKGROUND: Concerns about the effectiveness of condoms in preventing sexually transmitted diseases have been raised. Data are lacking on condom failure and its associated factors among sex workers in Southeast Asia. GOAL: To assess factors associated with condom breakage and slippage. STUDY DESIGN: A prospective study on condom breakage and slippage over a 1-day period was conducted among 219 female brothel-based sex workers in Singapore in 1997. RESULTS: Condom breakage and slippage rates among 1,885 episodes of condom use were 1.2% (95% CI, 0.7-1.8) and 2.1% (95% CI, 1.2-3.0), respectively. After adjusting for intracluster effects and confounders, condom breakage and slippage were significantly associated with duration of sex work and spontaneity of clients to use condoms. CONCLUSION: Condom use among sex workers should be promoted in view of the low failure rates. Strategies to reduce condom breakage and slippage should be directed at sex workers with increased risk of condom failure.

Adult↗
PubMed1999

Sexually transmitted diseases and condom use among female freelance and brothel-based sex workers in Singapore.

BACKGROUND AND OBJECTIVES: Most studies in Asia exclude freelance female sex workers because of difficulties in access and the illegality of their work. Data are lacking on their risk behaviors. GOAL: To compare sexually transmitted disease (STD) rates, condom use, and health screening behavior between freelance and brothel-based sex workers in Singapore. STUDY DESIGN: This is a cross-sectional survey of 111 free-lance sex workers arrested from November 1996 to March 1997 for illicit prostitution and 333 randomly selected brothel-based sex workers. All were tested for STDs. RESULTS: STDs were significantly more prevalent among freelance than brothel-based sex workers (34.8% vs. 24.0%). Inconsistent condom use was significantly higher among freelance than brothel-based sex workers and was significantly associated with younger age, decreasing number of clients, and perception of non-condom use among peers. CONCLUSION: Educational programs to promote condom use should target freelance sex workers and their clients.

Adult↗
PubMed1999

A prospective study of pharyngeal gonorrhoea and inconsistent condom use for oral sex among female brothel-based sex workers in Singapore.

Oral sex among female sex workers in Singapore has risen sharply from 27.1% in 1992 to 81.7% in 1997. A prospective cohort study was carried out on 724 female brothel-based sex workers who practised oral sex, to determine the risk of contracting pharyngeal gonorrhoea through inconsistent condom use. The prevalence of consistent condom use for oral sex was 70.4% compared to 96.8% for vaginal sex. One hundred and twenty-nine (17.8%) were lost to follow up because they quit prostitution. The other 595 sex workers were followed up for a maximum period of 6 months. Thirty-eight (5.2%) sex workers contracted pharyngeal gonorrhoea compared to 2.5% who contracted cervical gonorrhoea. Sex workers with inconsistent condom use for oral sex were 17.1 times (95% CI: 8.0-36.5) more likely than consistent condom users to develop pharyngeal gonorrhoea, after controlling for ethnic group, class and number of clients. STD control programmes for sex workers should place stress on consistent condom use for oral sex.

Adult↗
PubMed1999

Use of ligase chain reaction and polymerase chain reaction on urine specimens to detect Chlamydia trachomatis infections in a sexually transmitted diseases clinic in Singapore.

This study was done to assess the specificity and sensitivity of the DNA amplification assays of ligase chain reaction (LCR) and polymerase chain reaction (PCR) on urine specimens to detect Chlamydia trachomatis infections in both male and female patients seen at a sexually transmitted diseases (STD) clinic in Singapore, compared with other diagnostic methods currently in use. A total of 100 patients were selected; 50 male patients diagnosed with non-gonococcal urethritis based on symptoms and a positive Gram-stained urethral smear and 50 female asymptomatic sex workers were assessed. Automated assays using LCR and PCR were used, and compared to enzyme immunoassays, chlamydial cell cultures and PCR of urethral and endocervical swab specimens. In male patients, LCR and PCR of urine specimens had sensitivities of 100%, compared to 87.0% for PCR of urethral swab specimen, 82.6% for enzyme immunoassay (EIA) and 91.3% for cell cultures. In female patients, LCR and PCR of urine samples achieved sensitivities of 77.8% and 88.9% respectively, compared with 55.6% for PCR of endocervical swab specimens, 22.2% for EIA and 66.7% for cell cultures. LCR and PCR of urine samples provided higher sensitivity compared to cell cultures, EIA and PCR of urethral and endocervical swab specimens. The use of LCR and PCR on urine as a non-invasive means of detecting chlamydial infections is viable, and may have a role to play in population-based screening programmes.

Adult↗
PubMed1999

An open label comparative study of azithromycin and doxycycline in the treatment of non-gonococcal urethritis in males and Chlamydia trachomatis cervicitis in female sex workers in an STD clinic in Singapore.

AIM OF STUDY: The aim of this study was to compare the clinical and microbiological efficacy of a single 1 gram dose of azithromycin against 1 week of doxycycline at 100 mg twice a day in the treatment of: (1) uncomplicated non-gonococcal urethritis (NGU) in male patients, and (2) culture proven Chlamydia trachomatis cervicitis in female sex workers. METHOD: The subjects were 53 male patients who attended the clinic and were diagnosed to have non gonococcal urethritis based on clinical symptoms and a urethral smear, and 63 female sex workers, who had both a positive enzyme immunoassay (EIA) test and Chlamydia trachomatis cultures. Follow-up visits were made at one and two weeks post-treatment to assess efficacy, subsequent relapse and presence of side effects. The male patients were also assessed at four weeks post treatment to determine default and reinfection rates. RESULTS: Both azithromycin (clinical cure rates 62.5% at one week, 86.4% at two weeks in male patients; 96.6% at two weeks in female sex workers) and doxycycline (clinical cure rates 65.4% at one week, 90.9% at two weeks in male patients; 100% at two weeks in female sex workers) were effective in treating non-gonococcal urethritis and chlamydial cervicitis. Both drugs were very effective in eradicating proven Chlamydia trachomatis infections, with success in 100% of cases of Chlamydia trachomatis NGU in males, and 96.6% and 100% cure rates, for azithromycin and doxycycline respectively, in female sex workers with cervicitis. There were no statistically significant differences between the two drugs in terms of clinical efficacy, influence on default rates or subsequent risk of reinfection. CONCLUSIONS: We conclude that a single dose of azithromycin is as effective as a one week course of doxycycline in treating non-gonococcal urethritis in males and in the elimination of Chlamydia trachomatis in females with cervicitis, with the added advantage of a convenient single dose that can be supervised.

Adolescent↗
PubMed1998

Organization and transmitter specificity of medullary neurons activated by sustained hypertension: implications for understanding baroreceptor reflex circuitry.

In situ expression of c-fos observed in response to phenylephrine (PE)-induced hypertension provided a basis for characterizing the organization and neurotransmitter specificity of neurons at nodal points of medullary baroreflex circuitry. Sustained hypertension induced by a moderate dose of PE provoked patterns of c-fos mRNA and protein expression that conformed in the nucleus of the solitary tract (NTS) to the termination patterns of primary baroreceptor afferents and in the caudal ventrolateral medulla (CVLM) to a physiologically defined depressor region. A majority of barosensitive CVLM neurons concurrently displayed markers for the GABAergic phenotype; few were glycinergic. Phenylephrine-sensitive GABAergic neurons that were retrogradely labeled after tracer deposits in pressor sites of the rostral ventrolateral medulla (RVLM) occupied a zone extending approximately 1.4 mm rostrally from the level of the calamus scriptorius, intermingled partly with catecholaminergic neurons of the A1 and C1 cell groups. By contrast, barosensitive neurons of the NTS were found to be phenotypically complex, with very few projecting directly to the RVLM. Extensive colocalization of PE-induced Fos-IR and markers for the nitric oxide phenotype were seen in a circumscribed, rostral, portion of the baroreceptor afferent zone of the NTS, whereas only a small proportion of PE-sensitive neurons in the NTS were found to be GABAergic. PE treatment parameters have been identified that provide a basis for defining and characterizing populations of neurons at the first station in the central processing of primary baroreceptor input and at a key inhibitory relay in the CVLM.

Animals↗
PubMed1998

Differential time- and dose-related effects of haemorrhage on tyrosine hydroxylase and neuropeptide Y mRNA expression in medullary catecholamine neurons.

Hypotensive haemorrhage induces nuclear Fos expression and upregulates tyrosine hydroxylase (TH) mRNA in catecholamine-containing cell groups of the rat medulla oblongata. To shed light on the significance of the coexistence of neuropeptide Y (NPY) in aminergic neurons, the impact of graded levels of haemorrhage on temporal changes in the expression of TH and NPY mRNAs was compared; concurrent staining for Fos permitted comparisons between cells that ostensibly were and were not targeted by the stimulus. A 15% haemorrhage provoked increased NPY expression in all medullary catecholamine cell groups except the A2; these changes were detected predominantly in Fos-immunoreactive neurons (Fos-ir) at later (2-4 h) time points. Upregulation of TH and NPY mRNAs in Fos-ir neurons followed distinct time courses, with NPY responses peaking more rapidly, particularly in the C1 and C2 cell groups. Adrenergic cell groups displayed greater maximal increases in NPY expression than the A1 noradrenergic cell group while the converse was true of TH mRNA response. Increasing the severity of haemorrhage resulted in more pronounced increases in both mRNA responses in each aminergic region. These findings indicate that haemorrhage differentially affects TH and NPY expression in medullary catecholamine cell groups that participate in the maintenance of cardiovascular homeostasis. The differential nature of these responses suggests them not to be a simple consequence of metabolic alterations pursuant to increased synaptic activity. The prompt and robust NPY mRNA responses in adrenergic neurons suggests a mechanism by which peptide content of these cell groups' terminal projections is defended.

Animals↗
PubMed1998

Sexual practices among men attending an anonymous HIV testing site in Singapore.

This study was undertaken to provide an empirical basis for planning safer sex interventions in Singapore by examining the sexual practices of men attending an anonymous HIV testing site. All male clients attending the testing site from January, 1996 to January 1997 were asked to complete an anonymous questionnaire concerning oral and anal sex with men as well as vaginal, oral and anal sex with women within the past year. Questionnaires were obtained from 251 male clients, ranging in age from 17 to 70 years (mean = 30.3). Of these 50.6% reported sex with women only, 39% with men only, 7.2% with both men and women and 3.2% with no one. Condom use was moderately high for anal and vaginal sex but low for oral sex. A risk index based on the riskiness of specific activities showed that bisexuals were the most likely to engage in high risk behaviour whereas homosexuals were the least likely. One factor in the greater riskiness of bisexuals' behaviour appeared to be a higher frequency of unprotected sex with women. These findings provide a preliminary portrait of sexual risk-taking among men in Singapore and suggest the need for continued emphasis on consistent condom use for penetrative sex as well as appropriate precautions for oral sex. The results also suggest the need to develop targeted interventions for bisexuals, particularly with respect to unprotected sex with women.

Adolescent↗