Biomedical subjects

W K Chan

Publications and source records attributed to W K Chan.

At least 73 records · Page 4Linked to original sources

PubMed1998

Starting thrombolytic therapy for patients with acute myocardial infarction in Accident and Emergency Department: from implementation to evaluation.

OBJECTIVE: To evaluate the effectiveness of initiating thrombolysis for patients with acute myocardial infarction (AMI) in the Accident and Emergency Department. METHODS: From January 1993 to December 1995, all AMI patients who were admitted to the United Christian Hospital and given thrombolytic therapy were studied. The patients' demographic data, time and mode of presentation, site of myocardial infarction, treatment modality and timing, and complications related to AMI or treatment were recorded prospectively in our AMI database. The frequency of thrombolysis administered in Accident and Emergency Department and Coronary Care Unit, as well as the median door-to-needle time (time interval between hospital arrival to initiation of thrombolytic therapy) were compared. Cases of inappropriate thrombolysis and complication were also analyzed. RESULTS: Over these 3 years, 257 patients received thrombolysis in the United Christian Hospital. The percentage of patients receiving thrombolysis in Accident and Emergency Department increased from 3.2% in 1993 to 12.3% in 1994, and to 39.4% in 1995. The median time interval between arrival to hospital and thrombolysis (door-to-needle time) was 25 minutes, compared with 81 minutes in the Coronary Care Unit. The door-to-needle time also improved over these 3 years: from 95 minutes in 1993 to 75 minutes in 1995 in Coronary Care Unit group, and from 35 minutes in 1993 to 20 minutes in 1995 in the Accident and Emergency Department group. Over these 3 years, 2 cases of inappropriate thrombolysis were reported but these did not result in any mortality. Four complications from thrombolytic therapy were reported, and these were managed appropriately by the staff in Accident and Emergency Department and did not result in mortality. CONCLUSIONS: Starting thrombolytic therapy in Accident and Emergency Department is safe and effectively decreases the door-to-needle time.

Emergencies↗

PubMed1998

OphthWeb---cost-effective telemedicine for ophthalmology.

'OphthWeb' is an ophthalmic electronic medical record that can be accessed locally and globally via the Internet. OphthWeb can provide secure multimedia patient data to doctors, patients, and health care providers at any time and in any place. Patients have secured access to their own records in the convenience of their homes or during any emergency at any time or place around the world. OphthWeb provides interactive educational information and answers frequently asked questions by way of multimedia images on the Worldwide Web. A data transmission trial was conducted between the Xiamen Eye Centre in the Fujian province in southern China and Singapore. Clinical records, voice messages, and fundus and slit-lamp images were transmitted from Xiamen, and an off-line dialogue by e-mail and Internet-relay chat was conducted. The time delay from transmission to receipt was 30 minutes, which would be adequate to respond to most ophthalmic emergencies. This pilot project will promote computer literacy among doctors, and inter-institutional interaction in the health care profession. OphthWeb can provide telemedicine and electronic medical records at a low cost and great convenience.

Journal Article↗

PubMed1998

Emergency defibrillation performed by coronary nursing staff: A pilot report.

The time taken to initiate defibrillation is a key factor in determining survival after cardiac arrest; all first-responding medical or paramedical personnel are thus recommended to receive training in defibrillation skills. We have recently established a working programme that allows trained coronary care nurses to defibrillate in emergencies. Prospective data collected from 1 October 1996 to 31 January 1997 showed that a total of 11 witnessed episodes of ventricular fibrillation or pulseless ventricular tachycardia occurred in nine patients, and were defibrillated by nurses. All the defibrillations were started within 1 minute of cardiac arrest. In five patients, defibrillation was commenced before the arrival of the crash team of doctors; three of the five patients survived. There were no violations of the resuscitation protocol or complications relating to defibrillation. Through programmed training in advanced cardiac life-support, coronary care nurses are capable of providing safe and prompt defibrillation. The importance of training and re-certification is also stressed.

Journal Article↗

PubMed1998

Proliferation and cell death in oligodendrogliomas.

The rates of cell proliferation and of cell loss influence the growth rate of a tumour and reflect genetic changes. We studied proliferation and apoptosis in oligodendrogliomas and their relationship to progression of the tumours. Thirty-two cases of oligodendroglioma were retrieved spanning a 10-year period. The diagnosis and grade were reviewed and follow-up data obtained. Mitotic index (MI) and apoptotic index (AI) were determined from haematoxylin and eosin (H & E) stained sections. A labelling index (LI) of proliferating cells was obtained using the MIB1 antibody to the Ki-67 antigen. A further index of apoptosis was obtained using in situ end-labelling of DNA strand breaks (TUNEL index, TI). Fourteen cases were graded as II, 18 as III (1993 WHO). LI was significantly higher in grade III than in grade II tumours (P < 0.01) but the difference in apoptotic indices between grades was not significant. There was a significant (P = 0.036) positive correlation between the logarithms of TI and LI. Construction of survival curves demonstrated a significant difference in survival according to histological grade (P < 0.05). Stratification of cases by LI alone did not predict significantly different survival outcomes, and apoptotic indices did not demonstrate a relationship to survival. A positive relationship was demonstrated between proliferation and apoptosis in oligodendrogliomas. The levels of apoptosis observed indicate that this phenomenon may have an important influence on the overall rate of tumour growth.

Adolescent↗

PubMed1998

Undiagnosed acute myocardial infarction in the accident and emergency department: reasons and implications.

Because acute myocardial infarction causes significant morbidity and mortality, a correct diagnosis in the accident and emergency department is important so that early treatment including thrombolytic therapy can be given. The aim of this study was to evaluate the reasons for missed diagnosis of acute myocardial infarction in the accident and emergency department, and the implications. All patients admitted to our coronary care unit in 1995 with the confirmed diagnosis of acute myocardial infarction were analysed retrospectively. The demographic data, clinical profiles, diagnosis made at the accident and emergency department and feasibility of thrombolytic therapy were assessed. Analysis of the electrocardiography by the accident and emergency department doctor and the coronary care unit doctor were also compared. Forty-three out of 159 patients (27.0%) with acute myocardial infarction were missed in the accident and emergency department. The diagnoses made were mostly angina or chest pain. Absence of chest pain (25.6%) [vs. 10.2% in correct diagnosis group, p < 0.05] and lack of ST elevation in electrocardiograph (62.8%) [vs. 18.1% in correct diagnosis group, p < 0.0001] were the main predisposing factors for missed diagnosis. Because of missed diagnosis, only 25.6% (vs. 67.2% in correct diagnosis group, p < 0.01) of patients were admitted to the coronary care unit. About one-third (34.9%) of missed diagnosis patients (vs. 6.0% in correct diagnosis, p < 0.01) did not receive thrombolytic therapy because of delayed diagnosis. In the missed diagnosis group, 34.8% of them might be avoidable, if electrocardiogram interpretation was more accurate. More education and training of the involved medical personnel might improve the overall situation.

Adult↗

PubMed1997

Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway.

In an effort to better understand the mechanism of toxicity of 2,3,7, 8-tetrachlorodibenzo-p-dioxin, we employed an iterative search of human expressed sequence tags to identify novel basic-helix-loop-helix-PAS (bHLH-PAS) proteins that interact with either the Ah receptor (AHR) or the Ah receptor nuclear translocator (ARNT). We characterized five new "members of the PAS superfamily," or MOPs 1-5, that are similar in size and structural organization to the AHR and ARNT. MOPs 1-4 have N-terminal bHLH and PAS domains and C-terminal variable regions. MOP5 contained the characteristic PAS domain and a variable C terminus; it is possible that the cDNA contains a bHLH domain, but the entire open reading frame has yet to be completed. Coimmunoprecipitation studies, yeast two-hybrid analysis, and transient transfection experiments demonstrated that MOP1 and MOP2 dimerize with ARNT and that these complexes are transcriptionally active at defined DNA enhancer sequences in vivo. MOP3 was found to associate with the AHR in vitro but not in vivo. This observation, coupled with the fact that MOP3 formed tighter associations with the 90-kDa heat shock protein than the human AHR, suggests that MOP3 may be a conditionally active bHLH-PAS protein that requires activation by an unknown ligand. The expression profiles of the AHR, MOP1, and MOP2 mRNAs, coupled with the observation that they all share ARNT as a common dimeric partner, suggests that the cellular pathways mediated by MOP1 and MOP2 may influence or respond to the dioxin signaling pathway.

Amino Acid Sequence↗

PubMed1997

Harvesting a lamellar graft from a corneoscleral button: a new technique.

PURPOSE: To describe a new technique for harvesting a lamellar graft from a corneoscleral button in the absence of an artificial anterior chamber. METHODS: Two layers of sterile fine-weave fabric were wrapped tightly around a glass orbital implant. The corneoscleral button was sutured firmly at its scleral rim onto the fabric. The lamellar graft then was dissected in the regular fashion. RESULTS: The lamellar graft was successfully obtained. During the dissection, the donor cornea and its supporting fabric-covered glass ball were easily handled, and there was minimal risk of perforation of the posterior lamella of the donor cornea. CONCLUSION: This simple technique allows a lamellar graft to be easily obtained from a corneoscleral button without specialized and expensive equipment.

Cornea↗

PubMed1997

Phase II study of megestrol acetate in the treatment of hepatocellular carcinoma.

This is a report of a phase II study of megestrol acetate (160 mg/day, orally) in the treatment of hepatocellular carcinoma (HCC). Forty-six patients with advanced HCC were studied and tumour response, changes in appetite, bodyweight, a feeling of well-being, survival and toxicity were evaluated. Thirty-two patients were able to be evaluated for response; there were no complete responders or partial responders. Twelve patients (38%) had stable disease and seven of these patients had a minor response with a median size reduction in the tumour of 18%. Twenty patients (62%) had progressive disease. Five of 24 (21%) patients had a median reduction in alpha-fetoprotein levels of 59 ng/mL. The overall median survival was 4 months (range 1 week to 27 months). Twenty of 32 (62%) patients had an increased appetite and feeling of well-being. Fourteen of 22 (64%) patients had a median lean bodyweight gain of 5 kg (range 1-14 kg). Toxicities were minimal. Tests for glucocorticoid receptors were performed in 10 patients. Four of five patients who were positive for glucocorticoid receptors in the tumour had a stable disease and all five patients who were negative for glucocorticoid receptors had progressive disease. Megestrol acetate had no significant effect on the tumour in HCC patients. However, megestrol acetate is useful in the palliative management of HCC patients, with improvements in appetite, bodyweight and a feeling of well-being with minimal side effects. Some patients had stable disease, a minor reduction of tumour size and a prolonged survival after megestrol acetate treatment and this response may be related to the presence of glucocorticoid receptors in the HCC tumour.

Aged↗

PubMed1997

Central diabetes insipidus in a newborn with deletion of chromosome 7q.

We report an infant with midline craniofacial defects and holoprosencephaly due to chromosome 46, XY, del (7) (pter-->q34) who presented at 1 week of age with central diabetes insipidus. The importance of hypothalamic-pituitary endocrine investigation in patients with this syndrome, and more generally, in patients with midline craniofacial malformation or holoprosencephaly is emphasized. As infants with chromosome 7q deletion bear close phenotypic resemblance to infants of Trisomy 13, chromosomal confirmation and karyotype banding is mandatory to establish an accurate diagnosis and for genetic counselling of their parents.

Abnormalities, Multiple↗

PubMed1997

Mandibular odontogenic fibrosarcoma. Case report.

A rare case of mandibular odontogenic fibroma is presented which transformed to a stage 1A odontogenic fibrosarcoma with a local recurrence after surgical resection and unusually delayed pulmonary metastases eight years later. Prolonged follow-up of these patients after complete surgical resection, including regular chest X-rays, is recommended.

Adult↗

PubMed1997

Penetrating keratoplasty for keratoconus.

Keratoconus is a common corneal dystrophy in which penetrating keratoplasty is an effective form of treatment. A retrospective study on patients with keratoconus who underwent penetrating keratoplasty in the Singapore National Eye Centre between 1991 and 1995 was undertaken to describe and characterise the patient population and the success of this procedure. Thirty-two penetrating keratoplasties for keratoconus in 32 eyes of 29 patients were identified. Twenty eyes of 20 patients had a postoperative follow-up period of at least 12 months (range 12 to 44 months). These eyes were specifically examined for success rate and complications. Of the 32 eyes in the study, 18 (56%) belonged to Indians patients and 23 (72%) belonged to male patients. In those eyes with 12 months or more of postoperative follow-up, the visual acuity of 16 (80%) eyes improved postoperatively, with 14 (70%) eyes having a best corrected visual acuity of 6/12 or better. There were no graft failures. Nine eyes (45%) had complications postoperatively. Five eyes underwent refractive surgery for correction of astigmatism. Useful vision of 6/60 or better was achieved within 1 week postoperatively in 8 (40%) of the eyes. The authors conclude that penetrating keratoplasty is a successful procedure in keratoconic eyes not correctable by conservative therapy. The incidence of postoperative complications were however not uncommon. Although the majority of these complications were treated successfully, severe complications such as retinal detachment and glaucoma were the main causes of poor visual outcome after penetrating keratoplasty for keratoconus.

Adolescent↗

PubMed1997

Efficient gene transfer into zebrafish skeletal muscle by intramuscular injection of plasmid DNA.

The ability of zebrafish skeletal muscles to internalize and express plasmid DNA was demonstrated using pCMVCAT1, a chloramphenicol acetyltransferase (CAT) construct driven by the human cytomegalovirus immediate early (CMV-IE) promoter. We found that CAT activity was correlated to the amount of plasmid DNA injected, with maximal expression at 5 micrograms of pCMVCAT1. CAT activity was also shown to increase steadily over the first seven days after injection, with high levels of CAT expression persisting up to one year. Intramuscular injection of CAT constructs driven by other viral promoters also resulted in high levels of CAT activity. Histochemical localization using a CMV beta-galactosidase construct confirmed that only myofibers at the site of injection expressed beta-galactosidase enzyme. The persistence and strong expression of injected plasmid constructs suggest that zebrafish may be a simple and readily accessible system for direct muscle injection studies.

Animals↗

PubMed1997

Molecular characterization of the murine Hif-1 alpha locus.

Hypoxia inducible factor 1 alpha (HIF-1 alpha) is a basic helix-loop-helix-PAS (bHLH-PAS) transcription factor that mediates certain cellular responses to low oxygen tension, iron chelators, Co2+, Ni2+, Mg2+, and low intracellular glucose concentration. Upon exposure to the above conditions, HIF-1 alpha is upregulated and heterodimerizes with the Ah receptor nuclear translocator (ARNT, also known as HIF-1 beta), the heterodimeric complex binds TACGTG-containing genomic enhancer elements, and activates transcription of target genes. As a first step in developing genetic models to study the biology related to cellular hypoxia, we have cloned the murine HIF-1 alpha cDNA, determined the tissue-specific expression of its mRNA, functionally analyzed its protein product, and characterized its promoter and its genomic structure. A comparison between the murine and human HIF-1 alpha protein sequence reveals 95%, 99%, and 83% identity in the bHLH, PAS, and variable domains, respectively. RNAse protection assays demonstrate that in adult mice, the mHIF-1 alpha mRNA is expressed at high levels in kidney, heart, brain, thymus, and placenta, with moderate expression in liver, spleen, testis, and lung and much lower expression in skeletal muscle testis. Northern blot analysis indicates that the mRNA of the murine HIF-1 alpha is transcribed in two forms, a major 4-kb species and a minor 5-kb species; both are present in all tissues examined. The Hif-1 alpha promoter is GC rich, does not have a TATA element near its transcriptional start site, and does not respond to hypoxia or Co2+. The mHIF-1 alpha structural gene is composed of 15 exons. The splice junction sites within the bHLH and the PAS domains of HIF-1 alpha gene are highly conserved with respect to a number of previously characterized members of the bHLH-PAS superfamily. However, unlike other bHLH-PAS genes, where the variable domain is encoded by 2 exons, the variable region of the mHIF-1 alpha gene is encoded by 7 exons. Furthermore, most of these splice junction sites in the variable region are conserved with that of HIF-2 alpha, a recently cloned hypoxia-responsive bHLH-PAS protein (also known as MOP2, EPAS1, and HLF). These data suggest that HIF-1 alpha, along with HIF-2 alpha, represents a new subclass of the bHLH-PAS superfamily.

Amino Acid Sequence↗

PubMed1997

Photorefractive keratectomy for the treatment of compound myopic astigmatism using the ablatable mask.

Eight eyes of 8 patients with compound myopic astigmatism were treated with excimer laser photorefractive keratectomy (PRK) using a hand-held ablatable mask in conjunction with the Summit excimer laser. The attempted correction ranged from -1.25 to -400 dioptres (D) of astigmatism and 0 to -8.00 D of myopia. All eyes had attained at least 6 months of postoperative follow-up. Five of the 8 eyes achieved an unaided visual acuity of 6/12 or better. Postoperative refractions ranged from -0.50 to -3.50 D of refractive cylinder and from +0.50 to -3.75 D of spherical error. Decentration of the ablation zone was encountered in 3 eyes due to shifts in patients' fixation. Technical difficulty with the use of the hand-held ablatable mask limited the widespread application of this procedure and it has now been superseded by newer excimer laser systems which can correct astigmatism without having to employ a mask. Despite this, because of the theoretical ability of the mask to correct any form of refractive error, the concept of the mask shape transfer process will remain as a potential alternative in refractive surgery, especially for correction of hyperopia and hyperopic astigmatism.

Adult↗

PubMed1996

A novel series of [2-[methyl(2-phenethyl)amino]-2-oxoethyl] benzene-containing leukotriene B4 antagonists: initial structure-activity relationships.

This report describes the synthesis of a new class of LTB4 receptor antagonists containing [2-[methyl(2-phenethyl)amino]-2-oxoethyl]benzene as a key binding domain for interaction with high-affinity LTB4 receptors. In addition to this binding domain, two other structural features, an acid function and a lipophilic group, are also required by these compounds for high binding affinity. Our studies indicate that maximal binding affinity in this series is controlled by the spatial relationship of these groups relative to one another. The structure-activity relationships are discussed. The most potent compound in this chemical series, (E)-5-[2-[methyl(2-phenethyl)-amino]-2-oxoethyl]-2-(benzyloxy)cinn amic acid (32), has an IC50 of 2 nM in a guinea pig spleen cell membrane assay. In the whole-cell human neutrophils binding assay, (Z)-5-[2-[methyl-(2-phenethyl)amino]-2-oxoethyl]-2-(benzyloxy)cinn amic acid (30) was the most potent compound with an IC50 of 50 nM.

Animals↗

PubMed1996

Structure-activity relationships study of two series of leukotriene B4 antagonists: novel indolyl and naphthyl compounds substituted with a 2-[methyl(2-phenethyl)amino]-2-oxoethyl side chain.

N-Methyl-N-phenethylphenylacetamide has been reported to be a key binding domain to LTB4 receptors. Here we describe the synthesis and structure-activity relationship (SAR) studies of two new series of LTB4 receptor antagonists in which the phenyl ring of this receptor binding domain is replaced with indole and naphthalene, respectively. Results of these studies indicate that, in addition to the 2-[methyl(2-phenethyl)amino]-2-oxoethyl moiety, the presence of an acid group and a lipophilic side chain, as well as the spatial relationship of these three functions, is crucial for high binding affinity with LTB4 receptors. Our SAR studies also reveal that an arenecarboxylic acid, or an enoic acid in which the carboxyl group is conjugated with the central ring, is the preferred polar group. The lipophilic side chain of the naphthyl series was found to tolerate minor variations, ranging from a phenylmethoxy group to phenyl and alkyloxy groups. The most active compounds are 2-ethyl-3-[1-[2-[methyl(2-phenethyl) amino]-2-oxoethyl]-5-(phenylmethoxy)indol-3-yl]propenoic+ ++ acid (4g) of the indolyl series and 4-[2-[methyl(2-phenethyl)amino]-2-oxoethyl]-8-(phenylmethoxy )-2-naphthalenecarboxylic acid (2a) or the naphthyl series, with IC50 of 8 and 4.7 nM respectively, in the receptor binding assay using intact human neutrophils.

Acrylates↗

PubMed1996

Phase II study of flutamide in the treatment of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a male predominant disease and may be an androgen-dependent or androgen-responsive tumor. This Phase 11 study was designed to investigate the clinical activity and toxicity of flutamide in the treatment of patients with advanced HCC. METHODS: Thirty-two patients with measurable advanced HCC were studied. Flutamide, 750 mg per day, was administered orally for 8 weeks. Ten patients died before repeat tumor measurements could be performed. RESULTS: Twenty-two patients were evaluable for response and toxicities. There were no complete responses nor partial responses. Nine of 22 patients (41%) had stable disease and 13 patients (59%) had progressive disease. Serum alpha-fetoprotein was reduced in three patients. The median survival was 10 weeks (range, one to 35 weeks). Toxicities were minimal and tolerable. CONCLUSIONS: Flutamide is not effective in the treatment of advanced HCC. Clinically, HCC may not be an androgen-responsive tumor. Other new methods of treatment of HCC warrants future clinical investigations.

Adult↗

PubMed1996

A pharmacokinetic study with the high-dose anticancer agent menadione in rabbits.

The aim of this investigation was to assess the pharmacokinetic properties of high-dose menadione (VK3), as an anticancer agent, in plasma and red blood cells (RBCs) in rabbits. An extremely high dose of 75 mg menadiol sodium diphosphate (Synkayvite) was intravenously injected. HPLC analysis was applied to measure the major metabolite, menadione, VK3. The kinetic properties of VK3 in both plasma and red blood cells showed a short elimination half-life, high clearance, and large volume of distribution in plasma and RBCs. The mean elimination t1/2 values of menadione in plasma and in RBCs were 27.17 +/- 10.49 min and 35.22 +/- 11.82 min, respectively. The plasma clearance (CL/F) of VK3 was 0.822 +/- 0.254 L min-1. The systemic clearance in RBCs was 0.407 +/- 0.152 L min-1. The apparent volume of distribution (Vd/F) in plasma was 30.833 +/- 12.835 L and that in RBCs 20.488 +/- 9.401 L. The plasma AUC was 32.453 +/- 9.785 micrograms min mL-1 and that of RBCs 67.219 +/- 24.449 micrograms min mL-1. Menadiol was rapidly biotransformed to menadione in blood. The formation rate constant (kf) of menadione in plasma was 0.589 +/- 0.246 min-1, and that of RBCs 1.520 +/- 1.345 min-1. Through this study the estimated menadione dosage needed to maintain a plasma level of 1 microgram mL-1 for anticancer purposes was 19.7 mg kg-1 every hour.

Animals↗