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Biomedical subjects

E H Wong

Publications and source records attributed to E H Wong.

At least 19 recordsLinked to original sources
PubMed2006

Predictors of serious bacterial infection in children aged 3 to 36 months with fever without source.

INTRODUCTION: Children commonly present with fever without source yet there is no reliable and consistent method of identifying those at risk of serious bacterial infection. In this study, we sought to identify predictors of serious bacterial infection in children aged between three to 36 months with fever without source. METHODS: Inpatient records of all children aged three to 36 months admitted from the Emergency Department of Singapore's main paediatric hospital between October 2001 to February 2002 with International Classification of Diseases (ninth revision) diagnosis codes 038 (septicaemia), 079 (viral fever), or 780 (pyrexia of unknown origin), were retrieved and reviewed. Patients identified as having fever without source were enrolled. RESULTS: Of 86 enrolled children, 17 (19.8 percent) had serious bacterial infection. Duration of fever and white blood cell count were found to be significant predictors. Children with white blood cell count equal to or greater than 16,000/cubic mm had 6.9 times (95 percent confidence interval [CI] is 1.7 to 28.4) increased risk of serious bacterial infection, while children with fever of duration exceeding three days before presentation had 3.8 times (95 percent CI is 1.1 to 13.1) increased risk of serious bacterial infection. A combination of white blood cell count less than 16,000/cubic mm and duration of fever three days or less had a negative predictive value of 1.0 (95 percent CI is 0.88 to 1.0) and a sensitivity of 1.0 (95 percent CI is 0.82 to 1.0). CONCLUSION: The two identified predictors offer an estimate of the risk of serious bacterial infection in children aged three to 36 months with fever without source.

Bacterial Infections↗
PubMed2005

Adjuvant sequential chemotherapy and radiotherapy in uterine papillary serous carcinoma.

PURPOSE: To evaluate the efficacy and toxicity of adjuvant combination of sequential chemotherapy followed by radiotherapy in uterine papillary serous carcinoma (UPSC). METHODS AND MATERIALS: From April 1994 to June 2003, 26 patients (median age 61.7 years, range 46.9-78.4) with UPSC were treated with a platinum-based chemoradiation protocol after definitive surgery. 9 patients were assigned as stage I (35%), 4 were stage II (15%), 11 were stage III (42%), and 2 were stage IV (8%) according to the FIGO staging for gynecological cancers. All patients underwent total hysterectomy, salpingo-oophorectomy, pelvic +/- perioartic lymph nodes dissection/sampling, omentectomy, and peritoneal washing. The adjuvant chemoradiation protocol consists of 4 cycles of platinum-based chemotherapy followed by pelvic irradiation and vaginal vault brachytherapy. In selected stage I patients with no or minimal myometrial invasion, only vault brachytherapy was given after adjuvant chemotherapy. RESULTS: After a median follow-up of 28 months (range 9-113 months), 14 (54%) patients were alive and free of disease. 12 out of these 14 patients were FIGO stage I/II. 9 patients (35%) had died (8 from distant metastases). The Kaplan-Meier 2-year and 5-year survival estimates were 69.5% and 57%, respectively. Only 4 (15%) patients had pelvic recurrence. None of the patients developed local vault recurrence. The treatment was well tolerated, only 1 patient developed congestive cardiac failure from the chemotherapy and 6 patients had grade 2 peripheral neuropathy on follow-up. CONCLUSION: In our series of UPSC patients treated with adjuvant chemotherapy followed by radiotherapy, local control can be achieved in a majority of patients. Distant failure remains the major cause of mortality. Further investigations into finding a more effective systemic therapy are required if improvement in outcome for this form of uterine cancer is to be achieved.

Aged↗
PubMed2005

Faecal prevalence of extended-spectrum Beta-lactamase (ESBL)-producing coliforms in a geriatric population and among haematology patients.

Antimicrobial resistance to the extended-spectrum cephalosporins is increasingly reported worldwide. In the local setting, nosocomial infections with multi-resistant Gram-negative bacilli are not uncommon and are a growing concern. However, there is limited data on the carriage rates of such organisms in the local setting. In May 2001, a prospective study was carried out to determine the enteric carriage rates of ceftazidime-resistant Gram negative bacilli (CAZ-R GNB) among residents of nursing homes and from in-patients of the geriatric and adult haematology wards of University Malaya Medical Centre. Ceftazidime-resistant Gram-negative bacilli (CAZ-R GNB) were detected in 25 samples (30%), out of which 6 were from nursing home residents, 5 from geriatric in-patients and 14 from the haematology unit. A total of 28 CAZ-R GNB were isolated and Escherichia coli (10) and Klebsiella pneumoniae (7) were the predominant organisms. Resistance to ceftazidime in E. coli and Klebsiella was mediated by extended-spectrum beta-lactamases (ESBLs). Although the majority of the CAZ-R GNB were from patients in the haematology ward, the six nursing home residents with CAZ-R GNB were enteric carriers of ESBL-producing coliforms. Prior exposure to antibiotics was associated with carriage of ESBL organisms and to a lesser extent, the presence of urinary catheters.

Aged↗
PubMed2003

Breath-hold fast recovery fast spin echo versus conventional non-breath-hold fast spin echo T2-weighted MR imaging of focal liver lesions.

INTRODUCTION: We compare the breath-hold fast recovery fast spin echo (BHFRFSE) T2-weighted and non-breath-hold fast spin echo (NBHFSE) T2-weighted sequences in image quality and lesion characterisation of focal liver lesions. MATERIALS AND METHODS: Fat-suppressed T2-weighted magnetic resonance (MR) images obtained with the 2 sequences (BHFRFSE and NBHFSE) in 79 patients with 113 liver lesions were analysed retrospectively. The image quality and nature of the lesions were evaluated by 2 experienced radiologists. RESULTS: Based on receiver operating characteristic curve analysis, lesion characterisation was comparable for both sequences. The image quality of BHFRFSE was significantly better than that of NBHFSE. The NBHFSE missed 4 malignant lesions while BHFRFSE missed 2 malignant lesions. CONCLUSION: BHFRFSE performs similarly to NBHFSE in image quality and liver lesion characterisation.

Adult↗
PubMed2001

Rational design and assembly of M(2)M'(3)L(6) supramolecular clusters with C(3h) symmetry by exploiting incommensurate symmetry numbers.

A rational approach to heterometallic cluster formation is described that uses incommensurate symmetry requirements at two different metals to control the stoichiometry of the assembly. Critical to this strategy is the proper design and synthesis of hybrid ligands with coordination sites selective toward each metal. The phosphino-catechol ligand 4-(diphenylphosphino)benzene-1,2-diol (H(2)L) possesses both hard catecholate and soft phosphine donor sites and serves such a role, using soft (C(2)-symmetric) and hard (C(3)-symmetric) metal centers. The ML(3) catecholate complexes (M = Fe(III), Ga(III), Ti(IV), Sn(IV)) have been prepared and characterized as C(3)-symmetry precursors for the stepwise assembly (aufbau) of heterometallic clusters. While the single-crystal X-ray structure of the Cs(2)[TiL(3)] salt shows a C(1) mer-configuration in the solid -state, room-temperature solution NMR data of this and related complexes are consistent with either exclusive formation of the C(3)-fac-isomer with all PPh(2) donor sites syn to each other or facile fac/mer isomerization. Coordination of these [ML(3)](2)(-) (M = Ti(IV), Sn(IV)) metallaligands via their soft P donor sites to C(2)-symmetric PdBr(2) units gives exclusively pentametallic [M(2)Pd(3)Br(6)L(6)](4)(-) (M = Ti, Sn) clusters. These clusters have been fully characterized by spectral and X-ray structural data as C(3h) mesocates with Cs(+) or protonated 1,4-diazabicyclo[2.2.2]octane (DABCO.H(+)) cations incorporated into deep molecular clefts. Exclusive formation of this type of supramolecular species is sensitive to the nature of the counterions. Alkali cations such as K(+), Rb(+), and Cs(+) give high-yield formation of the respective clusters while NEt(3)H(+) and NMe(4)(+) yield none of the desired products. Extension of the aufbau assembly to produce related [M(2)Pd(3)Cl(6)L(6)](4)(-), [M(2)Pd(3)I(6)L(6)](4)(-), and [M(2)Cr(3)(CO)(12)L(6)](4)(-) (M = Ti, Sn) clusters has also been realized. In addition to this aufbau approach, self-assembly of several of these [M(2)Pd(3)Br(6)L(6)](4)(-) clusters from all eleven components (two M(IV), three PdBr(2), six H(2)L) was also accomplished under appropriate reaction conditions.

Journal Article↗
PubMed2001

Is second-order spatial loss in amblyopia explained by the loss of first-order spatial input?

The purpose of the study was to determine whether amblyopes show detection loss for second-order spatial information, and if present, whether the loss is explained by the loss of first-order spatial input. We psychophysically determined detection thresholds for the amblyopic and non-amblyopic eyes of five adult amblyopes and the dominant eyes of three control observers. We found that four amblyopic eyes and two non-amblyopic eyes showed second-order loss relative to the control eyes. The second-order loss was greater than the first-order loss at the carrier spatial frequency (first-order input). The extra second-order loss indicates an early amplification of cortical neural loss that we speculate is due to deficient binocular input to second-order neurons.

Adult↗
PubMed2001

Common discriminative stimulus properties in rats of muscarinic antagonists, clozapine and the D3 preferring antagonist PNU-99194a: an analysis of possible mechanisms.

Dopamine D3 receptors have been implicated in the aetiology of schizophrenia and the actions of antipsychotic drugs. The initial studies reported here assessed the involvement of such receptors in the in vivo actions of the atypical antipsychotic clozapine and the putative D3-preferring antagonist PNU-99194A in drug discrimination assays. Rats trained to discriminate clozapine consistently generalized to PNU-99194A in two separate studies. However, four other putative D3-preferring antagonists (PD 152255, (+)-S14297, nafadotride and (+)-AJ 76) did not induce generalization to clozapine. In rats trained to discriminate PNU-99194A, which has been suggested to induce a stimulus mediated specifically by D3 antagonism, the D3-preferring antagonist (+)-UH 232 and clozapine both induced full generalization. However, the PNU-99194A-trained animals also generalized fully to the muscarinic antagonists scopolamine and trihexyphenidyl. A possible explanation for the symmetrical generalization observed between clozapine and PNU-99194A is that these drugs have common muscarinic antagonist actions, since muscarinic antagonists have been reported to substitute for clozapine in numerous prior studies. However, in vitro receptor binding studies with M1-M5 receptors indicated that (with the possible exception of the M4 receptor), no muscarinic receptor subtype had high affinity for both clozapine, PNU-99194A and scopolamine. In addition, other binding studies indicated that whereas clozapine and PNU-99194A had high affinity for the D3 receptor, scopolamine did not. It is therefore concluded that: (1) The generalization seen between clozapine, PNU-99194A and muscarinic antagonists may be mediated by common effects 'downstream' from either muscarinic or D3 receptors; (2) D3 antagonism does not play a critical role in the clozapine stimulus (since D3-preferring antagonists did not consistently induce generalization to clozapine); (3) although D3 antagonism plays a role in the PNU-91994A stimulus (since the D3-preferring antagonist (+)-UH 232 induced full generalization, in accord with results from prior studies with other D3-preferring antagonists, the PNU-99194A stimulus also has commonalities with that induced by muscarinic antagonists and clozapine. The in vivo differences observed between PNU-99194A and other D3-preferring antagonists should be borne in mind when this agent is used as a tool to study D3 receptor functioning in vivo. The similarities between the PNU-99194A and clozapine stimuli suggest tentatively that compounds with a profile like PNU-99194A may have antipsychotic actions similar to clozapine. Some preclinical data are suggestive of such effects of PNU-99194A.

Animals↗
PubMed2001

Deep cerebral infarcts extending to the subinsular region.

BACKGROUND AND PURPOSE: We sought to determine the clinical and radiological features and pathogenesis of deep cerebral infarcts extending to the subinsular region (DCIs). METHODS: - We defined DCIs as subcortical infarcts extending between the lateral ventricle and the subinsular region with a paraventricular extent >1.5 cm and a subinsular extent of at least one third of the anteroposterior extent of the insula. We identified patients by review of imaging records and noted the clinical information, risk factors, and investigations. We compared risk factors and clinical features between DCIs and "internal border zone" infarcts restricted to the paraventricular region. RESULTS: - Eight patients were studied. The typical clinical features of DCIs were hemiparesis, aphasia, dysarthria, and dysphagia. Aphasia was seen in 3 of 5 patients with left-sided infarcts. Six of 8 patients (75%) had hypoperfusion as a possible pathogenetic factor (carotid occlusion in 4, surgical clipping of MCA in 1, low ejection fraction in 1), and 3 patients (38%) had cardioembolism as a possible pathogenetic factor (atrial fibrillation in 2, low ejection fraction in 1). One patient (12%) had no cause for stroke. Clinical features were similar to those for paraventricular infarcts. Carotid occlusion was more frequent (P=0.04), and there was a trend toward a higher frequency of hypertension (P<0.1) and smoking with DCIs than with paraventricular infarcts. DCIs were located in a deep vascular border zone. CONCLUSIONS: - The clinical features and pathogenesis of DCIs overlap with those of internal border zone paraventricular infarcts. Hypoperfusion may give rise to DCIs since large-artery occlusion is their main risk factor. The larger size of DCIs compared with paraventricular infarcts may relate to a poorer collateral blood supply.

Aged↗
PubMed2001

Intrinsic motivation among regular, special, and alternative education high school students.

This study examined motivationally related variables among three types of high school students. In particular, students' perceptions of competence, control, parental autonomy support, teacher autonomy support, peer autonomy support, and academic coping were investigated. Two hundred fifty-one juniors and seniors (104 regular education, 93 alternative education, and 54 special education) from a large Southern California school district participated. Significant group differences were found on measures of perceived competence, academic coping, and parental autonomy support. Specifically, regular education students had a higher level of self-reported academic competence than did special education students. Further, regular education and special education students reported that their parents were more involved in their lives as compared with alternative education students. Finally, regular education students reported a higher level of academic anxiety than did special education and alternative education students; however, regular education students had the highest level of positive coping. The implications of these findings are discussed.

Achievement↗
PubMed2000

Testing the disinhibition hypothesis of epileptogenesis in vivo and during spontaneous seizures.

The "disinhibition" hypothesis contends that (1) seizures begin when granule cells in the dentate gyrus of the dorsal hippocampus are disinhibited and (2) disinhibition occurs because GABAergic interneurons are excessively inhibited by other GABAergic interneurons. We tested the disinhibition hypothesis using the experimental model that inspired it-naturally epileptic Mongolian gerbils. To determine whether there is an excess of GABAergic interneurons in the dentate gyrus of epileptic gerbils, as had been reported previously, GABA immunocytochemistry, in situ hybridization of GAD67 mRNA, and the optical fractionator method were used. There were no significant differences in the numbers of GABAergic interneurons. To determine whether granule cells in epileptic gerbils were disinhibited during the interictal period, IPSPs were recorded in vivo with hippocampal circuits intact in urethane-anesthetized gerbils. The reversal potentials and conductances of IPSPs in granule cells in epileptic versus control gerbils were similar. To determine whether the level of inhibitory control in the dentate gyrus transiently decreases before seizure onset, field potential responses to paired-pulse perforant path stimulation were obtained from the dorsal hippocampus while epileptic gerbils experienced spontaneous seizures. Evidence of reduced inhibition was found after, but not before, seizure onset, indicating that seizures are not triggered by disinhibition in this region. However, seizure-induced depression of inhibition may amplify and promote the spread of seizure activity to other brain regions. These findings do not support the disinhibition hypothesis and suggest that in this model of epilepsy seizures initiate by another mechanism or at a different site.

Animals↗
PubMed2000

Reboxetine: a pharmacologically potent, selective, and specific norepinephrine reuptake inhibitor.

BACKGROUND: Reboxetine is a potent antidepressant, with efficacy comparable to that of imipramine, desipramine, and fluoxetine, and has improved side-effect profile. The basis of its efficacy and improved tolerability is sought through studies of reboxetine in a number of pharmacological models of depression. METHODS: Pharmacological selectivity for uptake systems was defined by uptake and binding assays for the three monoamine uptake sites. Specificity was determined in 39 different receptor and 6 enzyme assays. In vivo selectivity was defined by measurement of neuronal firing rates in the locus coeruleus, dorsal raphe, and substantia nigra. Reserpine-induced blepharospasm and hypothermia, clonidine-induced hypothermia, defined reboxetine's in vivo pharmacology. Reboxetine's antidepressant potential was evaluated behaviorally by the tail-suspension test, forced swimming, and the DRL72 operant responding test. RESULTS: Reboxetine is a potent, selective, and specific norepinephrine reuptake inhibitor (selective NRI) as determined by both in vitro and in vivo measurements. Unlike desipramine or imipramine, reboxetine has weak affinity (Ki > 1,000 nmol/L)for muscarinic, histaminergic H1, adrenergic alpha1, and dopaminergic D2 receptors. In vivo action of reboxetine is entirely consistent with the pharmacological action of an antidepressant with preferential action at the norepinephrine reuptake site. Reboxetine showed an antidepressant profile in all tests of antidepressant activity used. Significant decreases in immobility were observed in the tail suspension test and behavioral despair test. Increased efficiency in responding was observed in the DRL72 test. CONCLUSIONS: Reboxetine is a potent, selective, and specific noradrenergic reuptake inhibitor. It has a superior pharmacological selectivity to existing tricyclic antidepressants and selective serotonin reuptake inhibitors when tested in a large number of in vitro and in vivo systems. Given the pharmacological profile, reboxetine is expected to be a selective and potent tool for psychopharmacological research. The use of reboxetine in the clinic will also help clarify the role norepinephrine plays in depression.

Adrenergic Uptake Inhibitors↗
PubMed2000

ATP-sensitive potassium channels in freshly dissociated adult rat striatal neurons: activation by metabolic inhibitors and the dopaminergic receptor agonist quinpirole.

The characteristics of adenosine 5'-triphosphate (ATP)-sensitive K+ channels in acutely isolated striatal neurons from adult rats were examined. Neurons had a resting membrane potential of -53.9+/-1.2 mV (n=66), with evoked or spontaneous action potentials firing at 10+/-0.7 Hz, and large inwards and outwards whole-cell currents. In cell-attached patches with a high [K+] in the pipette, a voltage-independent, ATP-insensitive 16.5+/-1.5 pS channel was observed in 375 out of 452 cells. Bath application of Na+-azide (0.5-2 mM) to 108 neurons revealed another 145.7+/-3.5 pS (LKATP) channel in 65 neurons; this channel was blocked by tolbutamide. The LKATP channel exhibited a high open probability (Po, 0.8+/-0.05) at 0 mV pipette potential. Varying the pipette [K+] shifted the reversal potential of LKATP, showing the channel's K+ selectivity. Cytoplasmic ATP (ATPi) reversibly inhibited LKATP, with an inhibitory constant (Ki) of 0.12 mM. LKATP was sensitive to intracellular Ca2+ but insensitive to iberiotoxin. In 25% of cell-attached patches, the presence of quinpirole in the pipette opened a third type of channel (90.6+/-1.7 pS, termed D2KATP). Sulpiride, a dopamine D2-receptor antagonist, inhibited D2KATP. ATPi reversibly inhibited D2KATP, with a Ki of 0.212 mM. The Na+-azide- or quinpirole-induced current caused a tolbutamide-sensitive membrane hyperpolarization and a marked reduction in action potential frequency. We propose that ATP-sensitive K+ channels play a metabolism-dependent role in striatal neurons.

Action Potentials↗
PubMed1999

Nicergoline stimulates protein kinase C mediated alpha-secretase processing of the amyloid precursor protein in cultured human neuroblastoma SH-SY5Y cells.

We investigated the ability of the antidementia agents, nicergoline, aniracetam and hydergine to stimulate PKC mediated alpha-secretase amyloid precursor protein (APP) processing in cultured human neuroblastoma SH-SY5Y cells. Western immunoblotting of cell conditioned media using the Mabs 22C11 and 6E10 revealed the presence of 2 bands with molecular mass of 90 and 120 kDa, corresponding to possible alternatively glycosylated forms of secreted APP (APPs). Short-term (30 min and 2 h) treatment of cells with nicergoline gave an increased intensity of both bands, compared to non-treated cells. Maximal nicergoline effects, of the order of 150-200% over basal APPs release, were seen at concentrations between 1 and 10 microM. Under the same condition, 1 microM PdBu, used as a positive control, gave 500-1000% increases of basal APPs release. In contrast, aniracetam and hydergine, did not show any effect on APPs secretion. 2 h treatment with nicergoline had no effect on cellular full-length APP levels, as determined by immunoblotting of cell extracts with 22C11 and CT15 antibodies. Immunoblotting with PKC isoform specific antibodies of soluble and membrane fractions prepared from 2 h treated cells, showed that nicergoline (50 microM) and PdBu (1 microM) both induced translocation of PKC alpha, gamma and epsilon, but not PKC beta. The involvement of PKC in mediating nicergoline stimulated APPs release was also studied using specific inhibitors. 1 microM calphostin C, a broad range PKC inhibitor, significantly reduced both PdBu (1 microM) and nicergoline (10 microM) induced APPs release. In contrast, Go6976 (1 microM), a selective PKC alpha and beta1 inhibitor, as well as the cAMP-dependent protein kinase inhibitor, H89 (1 microM) were without effect. These results indicate that nicergoline can modulate alpha-secretase APP processing by a PKC dependent mechanism that is likely to involve the gamma and epsilon isoforms of this enzyme.

Amyloid Precursor Protein Secretases↗
PubMed1998

Enhanced delayed matching performance in younger and older macaques administered the 5-HT4 receptor agonist, RS 17017.

Recent evidence indicates that the 5-HT4 subtype of serotonin receptor may modulate central cholinergic activity in regions of the mammalian CNS important to memory such as the frontal cortex, hippocampus and amygdala. These receptors could represent targets for drugs designed for the symptomatic therapy of Alzheimer's disease (AD) and other disorders of memory. In the present study, the binding activity of RS 17017 (previously described as a selective 5-HT4 agonist) was assessed across a number of neurotransmitter receptors and binding sites, pharmacokinetic data were obtained, and the compound was evaluated in macaques for mnemonic effects via a computer-assisted delayed matching-to-sample task (DMTS). Binding data confirmed the 5-HT4 selectivity of the compound, while pharmacokinetic results revealed low oral bioavailability, but a large volume of distribution of the compound. Significant and reproducible improvements in DMTS accuracy were observed after oral administration of the compound across a dose-effect series in both younger and older monkeys. The results suggest that RS 17017 offers a potential for memory enhancement in disorders involving cognitive decline, and are consistent with a role for central 5-HT4 receptors in memory. Improvements in DMTS performance in aged monkeys may have particular implications for neurodegenerative conditions such as AD, whereas positive results in the younger monkeys indicate that RS 17017 (or similar compounds) may have additional potential in the therapeutics of memory disorders not necessarily associated with advanced age.

Aging↗