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Biomedical subjects

R K Chan

Publications and source records attributed to R K Chan.

At least 37 records · Page 2Linked to original sources

Long-term effects of nonpeptide vasopressin V2 antagonist OPC-31260 in heart failure in the rat.

The hormone arginine vasopressin (AVP) contributes to water retention and vasoconstriction in congestive heart failure (CHF) through effects at the V2 and V1a receptors, respectively. The effect of long-term V2 receptor (V2R) blockade using OPC-31260 was assessed in a rat model of postinfarction-induced CHF. Rats underwent coronary artery ligation or sham operation and were treated for 6 mo with oral OPC-31260 (10 mg . kg-1 . day-1) or vehicle. CHF was characterized by left ventricular remodeling and impaired systolic function, increased cardiac and lung weight, and elevated plasma atrial natriuretic peptide; plasma AVP and plasma renin activity were not increased. Chronic V2R blockade increased urine volume (P < 0.01) and decreased urine osmolality (P < 0.01) but had no natriuretic effects. V2R blockade did not activate the renin-angiotensin system but increased plasma AVP in CHF (P < 0.01). V2R blockade did not influence cardiac remodeling, cardiac function, or survival. These results suggest that AVP plays a major role in water retention through the renal V2R in a rat model of CHF. V2R blockade using OPC-31260 may represent an alternative to standard diuretic therapy in the management of water retention that characterizes heart failure.

Animals↗

Gonorrhoea treatment failure and ciprofloxacin resistance.

Ciprofloxacin-resistant strains of Neisseria gonorrhoeae have been on the increase over the past few years in Singapore and worldwide. The aim of this study is to correlate treatment failures with in vitro ciprofloxacin resistance of N. gonorrhoeae. A total of 694 patients attending the Department of STD Control (DSC) clinic in 1996 who were diagnosed to have gonococcal infection confirmed by culture were analysed. Treatment failure rates for ciprofloxacin were determined and the minimum inhibitory concentration (MIC) of ciprofloxacin were traced for all cases of treatment failure. The case notes of all patients who had strains with MICs of ciprofloxacin in the resistant (> or = 1 microg/ml) and less sensitive (0.125-0.5 microg/ml) range were also reviewed to determine the clinical outcome. Ciprofloxacin treatment failure rate was 1.7% (8/461) which was lower than the percentage of ciprofloxacin-resistant strains isolated in the laboratory. Of these 8 cases, 6 were resistant and 2 were less sensitive to ciprofloxacin. Cure rates with ciprofloxacin for resistant and less sensitive strains were 40% and 92% respectively. In conclusion, in vitro resistance to ciprofloxacin may not translate into clinical treatment failure. Clinical treatment failures, on the other hand, are also seen in less sensitive strains.

Anti-Infective Agents↗

Comparing treatment response and complications between podophyllin 0.5%/0.25% in ethanol vs podophyllin 25% in tincture benzoin for penile warts.

AIM: The aims of this study were to: 1) ascertain if podophyllin resin in 0.5% [PE(0.5%)] and 0.25% [PE(0.25%)] in ethanol (PE) self-applied sequentially for 3 days with 4 days break cycle is as effective as supervised podophyllin 25% in tincture benzoin (PB) applied in the clinic biweekly in treating penile warts and 2) ascertain if PE causes less skin irritation than PB. METHODS AND RESULTS: The clearance rate of penile warts was 36.4% (4/11) in PE (0.5%) treated group, 66.7% (4/6) in the PE (0.25%) treated group and 33.3% (6/18) for PB treated group after 1 week (ns). The wart clearance rate at 6 weeks for PE (0.5%) treated group, PE (0.25%) treated group and PB treated group were 81.8% (9/11), 100% (6/6) and 83.3% (15/17) respectively (ns). There were 47 individual warts on the penis of the 17 patients in the PE treated group and 58 individual warts on the penis of the 18 patients in the PB treated group. Based on the response of individual warts to the 2 treatment regimens, the clearance rate was 42.6% (20/47) for the PE treated group and 25% (15/56) for the PB treated group after 1 week treatment (ns). At 6 weeks follow-up, the clearance rate for the PE treated group and the PB treated group were 85.1% (40/47) and 73.2% (41/56) respectively (ns). Skin irritation including superficial erosions, pain and itch were observed in 47% (8/17) in patients treated with PE compared to 38.9% (7/18) in patients treated with PB (ns) during the 6 weeks follow-up period. The clearance rate of patients treated with PE (0.25%) was compared to those treated with PE (0.5%). Four out of six of PE (0.25%) treated patients had clearance of warts after 1 week and 100% clearance at the end of 6 weeks. None experienced any skin irritation. CONCLUSION: This study demonstrates that 0.5% podophyllin (and possibly 0.25% podophyllin) in ethanol is effective in eradicating penile warts. It can be used by patients for self-treatment at home with greater convenience and is more cost effective than the conventional podophyllin 25% in tincture benzoin paint.

Adult↗

The effect of polyethylene glycol (PEG) on the isolation of Chlamydia trachomatis in H-1 HeLa cells.

One hundred and ninety-six urethral and endocervical swabs were processed for isolation of C. trachomatis, using H-1 HeLa cells on shell vials, in the presence and absence of 7% PEG in the chlamydial overlay medium. The results were divided into three evaluable groups based on the number of inclusions per coverslip in the shell vials without PEG. The number of inclusions were compared with that of PEG-treated cultures using the paired t-test. The ranges for the three evaluable groups were one to ten, 11-100 and 101-1000 inclusions per coverslip. All three groups showed a significant increase (2.8- to 3.8-fold) in the number of inclusion bodies in the PEG-treated cultures compared to the untreated cultures.

Chlamydia trachomatis↗

Confirmatory serological testing of blood donors positive on TPHA screening in Singapore.

Seventy-two blood donors who were tested positive by the Singapore Blood Transfusion Service (SBTS) for Treponema pallidum haemagglutination (TPHA) test, were evaluated at the Department of Sexually Transmitted Diseases Clinic (DSC) between November 1994 to December 1996. All underwent syphilis serological testing, including rapid plasma reagin test (RPR), TPHA test and fluorescent treponemal antibody-absorption (FTA-Abs) test. All except one (98.6%) were confirmed TPHA positive by the DSC. Of the 71 TPHA-confirmed-positive donors, 53 (74.6%) were subsequently tested positive for FTA-Abs and 18 (25.4%) were tested negative for FTA-Abs. Twenty-two (31%) of the 71 TPHA-positive blood donors had reactive RPR and 49 (69%) had non-reactive RPR. Of the 22 TPHA-positive donors who had reactive RPR, 19 (86%) had positive FTA-Abs (13 late latent syphilis, 4 serological scar, one late congenital syphilis, one secondary syphilis), and 3 (14%) had negative FTA-Abs (all late latent syphilis). Of the 49 TPHA-positive donors who had non-reactive RPR, 34 (69%) had positive FTA-Abs (24 late latent syphilis, 9 serological scar, one late congenital syphilis) and 15 (31%) had negative FTA-Abs (12 late latent syphilis, 2 serological scar, one false-positive TPHA). Only one TPHA-positive donor referred by the SBTS subsequently turned out to have negative syphilis serology at the DSC. Overall, 68 (95.8%) TPHA-positive donors who had a past history of sexual exposure were managed as treated or untreated syphilis, regardless of their RPR or FTA-Abs results. However, FTA-Abs was found to be useful in the management of 3 (4.2%) TPHA-positive blood donors in the absence of a history of sexual exposures.

Adult↗

Unemployment and psychological health among Hong Kong Chinese women.

The impact of unemployment on psychological health, indexed by the General Health Questionnaire, was studied in 86 unemployed and 79 employed Chinese women in Hong Kong. As with findings reported in the West, the present results showed that the unemployed participants were more disturbed than their steadily employed peers. In addition, the prevalence rate of disturbance (54%) observed in the present sample of unemployed women is comparatively higher than those of Western samples reported previously. Implications of these preliminary findings for research on psychological aspects of unemployment among Hong Kong Chinese were discussed.

Adult↗

Corticotropin-releasing factor-binding protein ligand inhibitor blunts excessive weight gain in genetically obese Zucker rats and rats during nicotine withdrawal.

Elevation of the neuropeptide corticotropin-releasing factor (CRF) in the brain is associated with a reduction of food intake and body weight gain in normal and obese animals. A protein that binds CRF and the related peptide, urocortin, with high affinity, CRF-binding protein (CRF-BP), may play a role in energy homeostasis by inactivating members of this peptide family in ingestive and metabolic regulatory brain regions. Intracerebroventricular administration in rats of the high-affinity CRF-BP ligand inhibitor, rat/human CRF (6-33), which dissociates CRF or urocortin from CRF-BP and increases endogenous brain levels of "free" CRF or urocortin significantly blunted exaggerated weight gain in Zucker obese subjects and in animals withdrawn from chronic nicotine. Chronic administration of CRF suppressed weight gain nonselectively by 60% in both Zucker obese and lean control rats, whereas CRF-BP ligand inhibitor treatment significantly reduced weight gain in obese subjects, without altering weight gain in lean control subjects. Nicotine abstinent subjects, but not nicotine-naive controls, experienced a 35% appetite suppression and a 25% weight gain reduction following acute and chronic administration, respectively, of CRF-BP ligand inhibitor. In marked contrast to the effects of a CRF-receptor agonist, the CRF-BP ligand inhibitor did not stimulate adrenocorticotropic hormone secretion or elevate heart rate and blood pressure. These results provide support for the hypothesis that the CRF-BP may function within the brain to limit selected actions of CRF and/or urocortin. Furthermore, CRF-BP may represent a novel and functionally selective target for the symptomatic treatment of excessive weight gain associated with obesity of multiple etiology.

Animals↗

Appetite-suppressing effects of urocortin, a CRF-related neuropeptide.

The neuropeptide corticotropin-releasing factor (CRF) is well known to act on the central nervous system in ways that mimic stress and result in decreases in exploration, increases in sympathetic activity, decreases in parasympathetic outflow, and decreases in appetitive behavior. Urocortin, a neuropeptide related to CRF, binds with high affinity to the CRF2 receptor, is more potent than CRF in suppressing appetite, but is less potent than CRF in producing anxiety-like effects and activation. Doses as low as 10 nanograms injected intracerebroventricularly were effective in decreasing food intake in food-deprived and free-feeding rats. These results suggest that urocortin may be an endogenous CRF-like factor in the brain responsible for the effects of stress on appetite.

Animals↗

Prediction of outcome after revascularization in patients with poor left ventricular function.

BACKGROUND: In patients with poor left ventricular function, the determinants of outcome after revascularization are unknown. METHODS: We studied prospectively 57 patients with stable coronary artery disease and poor left ventricular function (left ventricular ejection fraction, 0.28 +/- 0.04) who underwent coronary artery bypass grafting. Clinical variables were assessed as predictors of outcome in all patients, and preoperative stress thallium-201 scintigraphic data were analysed in 37 patients. RESULTS: The operative mortality was 1.7%. At 12 months after operation, 46 of the 49 survivors were angina-free and 35 had fewer heart failure symptoms, but postoperative left ventricular ejection fraction (0.30 +/- 0.09) did not change significantly. Eighteen survivors had left ventricular ejection fraction improved by 0.05 or more (0.30 +/- 0.03 preoperatively, 0.40 +/- 0.05 postoperatively; p = 0.0001). The adjusted odds ratio of large reversible thallium-201 defects in predicting such outcome was 15 (95% confidence interval, 1.6 to 140), whereas other clinical variables had no predictive value. The transplantation-free 5-year survival was 73%. CONCLUSIONS: In patients with poor left ventricular function, surgical revascularization can be performed safely, with good symptomatic relief and long-term survival. One-year survival and improvement in left ventricular function is better in patients with large reversible defects on preoperative stress thallium-201 scintigraphy.

Aged↗

Comparison of dobutamine echocardiography and positron emission tomography in patients with chronic ischemic left ventricular dysfunction.

OBJECTIVES: The aim of this study was to correlate dobutamine-induced contractile reserve as detected by echocardiography with findings on positron emission tomography in patients with chronic ischemic left ventricular dysfunction. BACKGROUND: Contractile reserve induced by low dose dobutamine infusion has been proposed as a marker of myocardial viability. METHODS: Sixty patients with stable coronary artery disease and left ventricular dysfunction (mean ejection fraction [+/- SD] 29 +/- 10%) underwent transthoracic echocardiography with dobutamine infusion (up to 10 micrograms/kg body weight per min) and positron emission tomography with nitrogen-13 ammonia and fluorine-18 (F-18) fluorodeoxyglucose as a perfusion and a metabolic tracer, respectively. Regional wall motion, perfusion and metabolism were analyzed semiquantitatively by using a 16-segment model. Segments with F-18 fluorodeoxyglucose uptake > 50% were considered viable on positron emission tomography. RESULTS: After dobutamine infusion, hemodynamic variables changed significantly, and myocardial ischemia was evident in 17 patients. All 60 patients had dysfunctional myocardium considered viable on positron emission tomography (8 +/- 4 segments/patient), whereas 52 patients had dysfunctional myocardium with contractile enhancement by dobutamine echocardiography (4 +/- 2 segments/patient, p = 0.01). The extent of dysfunctional myocardium with contractile reserve appeared to correlate less closely with the total extent of viable dysfunctional myocardium identified by positron emission tomography than with the number of such segments associated with a pattern of perfusion-metabolism mismatch. CONCLUSIONS: In patients with chronic ischemic left ventricular dysfunction, echocardiography can be used to identify enhancement in the contractile function of viable dysfunctional myocardium after infusion of low dose dobutamine. In this study, the presence and extent of such enhancement were relatively less than the values obtained from positron emission tomography.

Coronary Disease↗

A study of treponema pallidum haemagglutination positive blood donors in Singapore.

The Treponema Pallidum Haemagglutination (TPHA) test has been used for screening of syphilis among blood donors in Singapore since September 1992. Among the 79 500 donations that were screened between September 1992 and December 1993, 191 were tested positive (incidence rate of 0.24%). Seventy-two donors (37.7%) were evaluated at the Department of Sexually Transmitted Disease Control clinic. Seventy-nine percent of these donors had high risk sexual exposure and 33.3% had a history of sexually transmitted diseases. Eighty-three percent of the donors were diagnosed to have late latent syphilis, 9.7% were diagnosed to have a serological scar and the remaining had secondary syphilis, early latent syphilis and a false positive reaction. At least 65.3% of these donors would have been missed if the reagin test was used alone as the screening test. Thus, the TPHA test is a good marker for screening those who have high risk sexual behaviour and it is a more sensitive test than the reagin test for screening blood donors.

Adult↗

Molecular detection of human immunodeficiency virus-1 infection among commercial sex workers using the polymerase chain reaction in Singapore.

We studied the sensitivity of polymerase chain reaction (PCR) for detecting early human immunodeficiency virus-1 (HIV-1) in sex workers. Blood samples of sex workers who attended our Sexually Transmitted Diseases clinic were tested for HIV infection by testing for the presence of HIV antibody and HIV-1 proviral DNA using PCR (with the Amplicor HIV-1 amplification kit, Roche) at 00 (when they first register to work as sex workers), 01 and 03 months after starting work. The objective was to detect HIV-1 using PCR in sex workers during the "window" period when their HIV antibody tests were still negative. Sixty-nine blood samples were PCR-tested at 00 month of which 8 were simultaneously positive for HIV antibody and PCR tests. Seventy-seven blood samples were tested at 03 month. We found that PCR test using the Amplicor HIV-1 amplification kit (Roche) to be sensitive in detecting HIV infection in sex workers but the test appeared not sensitive enough to detect HIV-1 infection during the "window" period. We were unable to detect any sex workers with PCR detectable HIV-1 before they seroconverted to become HIV antibody positive. The reason for the failure was attributed to the low infection rate among sex workers and possible lack of sensitivity of the Amplicor PCR/HIV-1 amplification kit to detect early HIV-1 infection. We are currently studying other PCR procedures to improve the sensitivity of the PCR test for HIV-1.

DNA, Viral↗

A1 catecholamine cell group: fine structure and synaptic input from the nucleus of the solitary tract.

Preembedding immunoperoxidase staining methods were used to characterize tyrosine hydroxylase-immunoreactive (TH-ir) elements in the caudal ventrolateral medulla, and to determine the extent to which neurons of the A1 cell group are directly innervated by projections of the nucleus of the solitary tract (NTS). TH-ir neurons in the A1 region were medium-sized and multipolar. They possessed rounded nuclei with infrequent invaginations, well-developed Golgi apparati, high cytoplasmic densities of mitochondria, and a low to moderate tendency for rough endoplasmic reticulum (RER) to align in parallel stacks. A1 cell bodies were commonly juxtaposed to TH-positive and TH-negative neurons, myelinated profiles, glia and/or vascular elements, but close membrane appositions were only seen with glial elements. Synaptic input to A1 neurons was predominantly asymmetric, provided virtually exclusively by non-TH-ir terminals, and directed principally to dendritic shafts; A1 somata are relatively sparsely innervated. In a second experiment, silver-intensified immunogold localization of TH-ir was combined with immunoperoxidase labeling for anterogradely transported Phaseolus vulgaris-leucoagglutinin (PHA-L), following tracer injections in the caudal aspect of the medial division of the NTS. These experiments revealed a small proportion of PHA-L-labeled axon terminals that made asymmetric contacts with dendritic shafts of TH-ir neurons. These results suggest that the fine structure and synaptic input of A1 neurons are somewhat distinct from that of rostrally situated C1 catecholamine cells. In addition, while they document a direct NTS-A1 projection that may participate in the interoceptive control of vasopressin secretion, the bulk of ventrolaterally directed projections from the caudomedial NTS contact noncatecholaminergic elements in the A1 region, some of which may correspond to so-called depressor neurons implicated in the baroreflex control of sympathetic outflow and vasopressin secretion.

Animals↗

Hemodynamic regulation of tyrosine hydroxylase messenger RNA in medullary catecholamine neurons: a c-fos-guided hybridization histochemical study.

Medullary catecholamine cell groups are involved in multiple modes of cardiovascular regulation and display indices of functional activation, including widespread c-fos expression, in response to hypotensive hemorrhage. Assessments of the impact of such challenges on transmitter-related gene expression are complicated by the biochemical and connectional heterogeneity that characterize these cell groups. Quantitative hybridization histochemical methods were used to follow the effects of 15% hemorrhage on levels of messenger RNA encoding tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, in medullary aminergic neurons; concurrent staining for nuclear Fos-immunoreactivity permitted comparisons between cells that ostensibly were and were not targeted by the challenge. Increased levels of tyrosine hydroxylase messenger RNA were detected in Fos-immunoreactive neurons in all cell groups examined. Mean maximal increases ranged between 133 and 192% of control values, and were attained within 0.5-1 h post-hemorrhage in noradrenergic (A1 and A2) cell groups, and at 2 h in adrenergic ones (C1, C2, and C2d or dorsal strip). By 4 h after the challenge, tyrosine hydroxylase messenger RNA levels in Fos-immunoreactive neurons in all cell groups had returned to control values. By contrast, tyrosine hydroxylase messenger RNA in non-Fos-immunoreactive cells either did not change significantly over the course of the experiment (C2 and C2d), or showed a rapid and transient increase, whose magnitude tended to be less than that seen in Fos-immunoreactive cells. c-fos messenger RNA was prominently induced in catecholaminergic neurons in each of the medullary cell groups examined at 0.5 h after hemorrhage, suggesting that the early tyrosine hydroxylase messenger RNA response to hemorrhage in non-Fos-immunoreactive cells preceded the capacity of responsive neurons to manifest detectable Fos protein expression. These findings indicate that hemorrhage up-regulates tyrosine hydroxylase messenger RNA levels in medullary catecholaminergic cell groups which have access to adaptive neuroendocrine and/or autonomic control systems. The approach employed here should prove of general utility in assessing the impact of environmental events on messenger RNA expression in connectionally heterogeneous cell groups that share a common biochemical phenotype.

Adrenergic Fibers↗

Assessment of coronary artery disease by dobutamine stress echocardiography (DSE).

BACKGROUND: Dobutamine stress echocardiography (DSE) is a new non-invasive imaging modality which combines two-dimensional echocardiography with cardiovascular stress induced by dobutamine infusion. Its use in patients with suspected or documented coronary artery disease (CAD) is currently under extensive investigation. AIMS: To illustrate the clinical utility, safety and diagnostic value of DSE. METHODS: One hundred and thirty-seven consecutive patients referred for DSE were studied. Eighty-four patients also underwent coronary angiography. RESULTS: Eleven patients (8%) did not undergo DSE because of poor image quality. Of the remaining 126 patients, 110 (87%) achieved their target heart rate or reached a pre-determined end point during DSE. Eight patients (6%) developed non-cardiac side effects during DSE, none of which required premature termination of the procedure. Cardiac arrhythmias were documented in 15 patients (12%) but only one required intervention. In 84 patients who underwent coronary angiography, DSE showed a sensitivity and specificity of 88% and 83%, respectively, in detecting the presence of, and 75% and 75%, respectively, in localising significant CAD. In 35 patients who underwent DSE after uncomplicated myocardial infarction, the positive and negative predictive values for cardiac events following infarction in a six-month followup period were 74% and 62%, respectively. CONCLUSIONS: DSE is a well tolerated, safe and useful test in detecting and localising significant CAD. It can also provide useful post-infarctional prognostic information.

Adult↗