PubMed Health⌕ Search

Biomedical subjects

T H Chan

Publications and source records attributed to T H Chan.

At least 19 recordsLinked to original sources
PubMed2006

Multiresolution wavelet analysis for efficient analysis, compression and remote display of long-term physiological signals.

Increased inter-equipment connectivity coupled with advances in Web technology allows ever escalating amounts of physiological data to be produced, far too much to be displayed adequately on a single computer screen. The consequence is that large quantities of insignificant data will be transmitted and reviewed. This carries an increased risk of overlooking vitally important transients. This paper describes a technique to provide an integrated solution based on a single algorithm for the efficient analysis, compression and remote display of long-term physiological signals with infrequent short duration, yet vital events, to effect a reduction in data transmission and display cluttering and to facilitate reliable data interpretation. The algorithm analyses data at the server end and flags significant events. It produces a compressed version of the signal at a lower resolution that can be satisfactorily viewed in a single screen width. This reduced set of data is initially transmitted together with a set of 'flags' indicating where significant events occur. Subsequent transmissions need only involve transmission of flagged data segments of interest at the required resolution. Efficient processing and code protection with decomposition alone is novel. The fixed transmission length method ensures clutter-less display, irrespective of the data length. The flagging of annotated events in arterial oxygen saturation, electroencephalogram and electrocardiogram illustrates the generic property of the algorithm. Data reduction of 87% to 99% and improved displays are demonstrated.

Algorithms↗
PubMed2006

Appropriateness of colonoscopy using the ASGE guidelines: experience in a large Asian hospital.

BACKGROUND: The is currently a heavy burden on endoscopy services worldwide and although guidelines for the appropriate use of esophagogastroduodenoscopy (EGD) have been well studied, there are few such studies with respect to colonoscopy and none for the Asia-Pacific region. This study aimed, firstly, to determine the 'appropriateness of colonoscopy' for procedures performed in the endoscopy unit of a large Asian hospital using the American Society of Gastrointestinal Endoscopy (ASGE) 2000 guidelines, and secondly, to determine predictive factors including 'appropriateness of colonoscopy' for positive findings and colorectal cancer (CRC). METHODS: A prospective cross-sectional study was carried out on consecutive colonoscopies performed in the University of Malaya Medical Center. The unit has an open-access endoscopy policy for doctors who work in the hospital. Referrals were from endoscopists (gastroenterologists and surgeon-endoscopists), primary care physicians and other specialists. The indication of a procedure referral was recorded and judged 'appropriate' or 'inappropriate' using the ASGE criteria. The colonoscopic findings were recorded and classified as positive (endoscopies showing any pathology that had direct therapeutic or prognostic consequences) or negative findings (endoscopies showing no pathology or minor pathologies). Predictive factors for positive findings and CRC were determined using multivariate analysis. RESULTS: Of 380 patients referred for colonoscopy, 220 (57.9%) were classified as appropriate according to the ASGE guidelines, and 49 (12.9%) as inappropriate. The remaining 111 patients (29.2%) presented with complaints and conditions that could not be categorized. The rate of appropriate referral was similar for all three categories of physician (endoscopists: 59.8%, primary care physicians: 48.1%, others: 51.1%). When referrals by endoscopists were substratified according to gastroenterologists and surgeon-endoscopists, the rate of appropriate referral among gastroenterologists (78.4%) was significantly higher than that of surgeon-endoscopists (56.1%) (P = 0.049), primary care physicians (P = 0.013) and 'others' (P = 0.009). The most common appropriate indications were unexplained Rectalbleeding (79 cases, 20.8%) followed by CRC surveillance (45 cases, 11.8%). The most common inappropriate indication was inappropriately timed colonic cancer surveillance (32 cases, 8.4%). Chronic constipation in 36 cases (9.5%) was the most common 'unlisted' indication. A positive colonoscopic finding was detected in 131 (34.5%) examinations and CRC was found in 36 patients (9.5%). Appropriateness of indication was not a predictive factor for positive findings or CRC and there was no difference in the proportion of cases with positive findings or CRC in the three 'appropriateness categories'. Multivariate analysis revealed that only Rectalbleeding and smoking were significant independent positive predictive factors for positive findings and CRC. CONCLUSION: The appropriateness of colonoscopy was not high among the different sources of referrals except for the subgroup of 'gastroenterologist'. Furthermore, the rates of positive findings and CRC among the cases with appropriate, inappropriate and unlisted indications did not differ. The ASGE guidelines will need to be modified for Asia to be of practical use.

Adult↗
PubMed2000

[Plague in the port of Mahajanga: 6 inhabitants out of 1000 carry the anti-F1 antibody in 1999].

The authors report the results of a randomized epidemiological survey aiming to assess the sero-prevalence of plague in the general population > or = 2-year-old in Mahajanga. In 656 sera tested (by ELISA), the prevalence of anti-F1 antibodies was found to be 6.1%@1000 inhabitants, close to the expected prevalence in the area, where plague reappeared in 1991 after 62 years of absence. The study also demonstrated that the shrew, Suncus murinus, is an important reservoir in the plague transmission in Mahajanga.

Adolescent↗
PubMed1999

Cytokinetics of a novel 1,2,3-triazene-containing heterocycle, 8-nitro-3-methyl-benzo-1,2,3,5-tetrazepin-4(3H)-one (NIME), in the human epithelial ovarian cancer cell line OVCAR-3.

The mechanism of action of the novel tetrazepinone 8-nitro-3-methyl-benzo-1,2,3,5-tetrazepin-4(3H)-one (NIME), structurally related to the antitumour drug temozolomide, was studied in the human ovarian tumour cell line OVCAR-3. NIME preferentially inhibited DNA synthesis over protein and RNA syntheses at 3 and 24 hr post-treatment. A Maxam-Gilbert sequencing assay showed that NIME induced barely detectable levels of guanine N7 alkylation in an isolated DNA strand, in contrast to temozolomide, a strong alkylating agent containing, like NIME, a cyclic 3-methyl-1,2,3-triazene moiety. Alkaline sucrose density-gradient sedimentation, at concentrations 2- to 10-fold lower than the ones used in the DNA sequencing assay, showed significant DNA damage in OVCAR-3 cells 24 hr after treatment with NIME. This was accompanied by a significant accumulation of cells in late S and G2M. Cell cycle arrest was transient and was reversed after 2-3 days following drug treatment. This was in agreement with bivariate bromodeoxyuridine/propidium iodide analysis, which showed that at 100 microM, a concentration at which the majority of the cells arrested in late S and G2M, a significant fraction of bromodeoxyuridine positive (S-phase) cells escaped the block. In an attempt to elucidate the mechanism underlying these effects, the degradation of NIME in cell culture medium was analyzed by GC-MS (gas chromatography coupled with mass spectrometry). The results showed that, in contrast to temozolomide, NIME did not convert to an open-chain alkyltriazene in cell culture medium, but to a major benzimidazole product, which exerted a minor effect on the cell cycle. This suggests that NIME, despite containing a 3-(alkyl)-1,2,3-triazene moiety, does not act by DNA alkylation but probably by generating a short-lived genotoxic species during its degradation to 6,5-benzofused derivatives.

Alkylation↗
PubMed1999

Tetrazepinones are equally cytotoxic to Mer+ and Mer- human tumor cell lines.

Human brain and colon tumor cell lines SF-188 (Mer+) and WiDR (Mer+), which express the DNA repair protein O6-methylguanine-DNA methyl transferase (MGMT), were 3- to 30-fold less sensitive to temozolomide, mitozolomide, and N, N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) than the MGMT-deficient tumor cells SF-126 (Mer-) and BE (Mer-). This differential sensitivity was not observed when these cells were exposed to the novel tetrazepinones PYRZ, NIME, QUINCL, and PYRCL, which contain, like temozolomide and mitozolomide, a ureido-triazene moiety. Flow cytometric studies revealed that temozolomide induced G2-M arrest in the Mer- cells, but exerted a minor effect on the cycle of the Mer+ cells. Similarly, mitozolomide (25-100 microM) induced a stronger S-phase arrest in the SF-126 cells than in the SF-188 cells. In the same dose range (25-100) BCNU induced a significant cell cycle accumulation in G22-M in the SF-126 cells but little in the SF-188 cell line. In contrast, the cell cycle effects of the tetrazepinones were independent of the cell phenotypes. When O6-benzylguanine (O6-BG) was used to deplete MGMT activity in the SF brain tumor cell lines, significant potentiation of temozolomide (67-fold), mitozolomide (7-fold), and BCNU (3-fold) was observed in the SF-188 cell line. By contrast, O6-BG did not potentiate PYRZ, PYRCL, QUINCL, and NIME. Moreover, an MGMT inhibitory assay showed that all the tetrazepinones were capable of inactivating MGMT in the SF-188 cell line, the strongest inhibitor being PYRCL. The results suggest that, unlike temozolomide, mitozolomide, and BCNU, the cytotoxicity of the tetrazepinones does not correlate with the alkylation of the O6 position of guanine and that the mechanism of MGMT inactivation by tetrazepinones may differ from that of hitherto known inhibitors.

Antineoplastic Agents, Alkylating↗
PubMed1998

Synthesis and structure-activity relationships of 2-pyrazinylcarboxamidobenzoates and beta-ionylideneacetamidobenzoates with retinoidal activity.

The structure-activity relationships of two series of novel retinoids (2-pyrazinylcarboxamidobenzoates and beta-ionylideneacetamidobenzoates) have been investigated by evaluating their ability to induce differentiation in both human promyelocytic leukemia (HL60) cells and mouse embryonal carcinoma (P19) cells. The most active compound (ED50 = 8.3 x 10(-9) M) of the 2-pyrazinylcarboxamidobenzoates is 4-[2-(5,6,7,8-tetrahydro-5,5,8, 8-tetramethylquinoxalyl)carboxamido]benzoic acid (9u), while the most active analogue of the beta-ionylideneacetamidobenzoates is 4-[3-methyl-5-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-(2E, 4E)-pentadienamido]benzoic acid (10a, ED50 = 3.2 x 10(-8) M). Our studies identify an absolute requirement for the carboxylic acid moiety on the aromatic ring to be para relative to the amide linkage for activity. Benzoate substitutions in the ortho position relative to the terminal carboxylate (9d,k,r) are well-tolerated; however, a methoxy substituent meta relative to the terminal carboxylate gives rise to only weakly active analogues (9x). Conformational studies (NMR, X-ray crystallography) of the 2-pyrazinylcarboxamidobenzoates indicate that the preferred conformation exhibits a trans-amide bond and an internal hydrogen bond between the quinoxaline N1 and HN amide which locks the torsional angle between C2 and CO in the s-trans conformation. N-Methylation (9y) results in loss of activity. Studies indicate that there is now a cis-amide bond present which redirects the carboxylate toward the pharmacophoric gem-dimethyl groups. The distance between the gem-dimethyl group and the terminal carboxylate appears to be too short to activate the retinoid receptor. N-Methylation in the beta-ionylideneacetamidobenzoate series (10c) also results in the formation of a cis-amide bond and loss of activity.

Animals↗
PubMed1998

Comparative studies between the effects of mitozolomide and two novel tetrazepinones PYRCL and QUINCL on NIH:OVCAR-3 cells.

UNLABELLED: Cytotoxicity, reduction of macromolecule synthesis and cell cycle perturbations by two novel 3-(2-chloroethyl)-tetrazepinones, PYRCL and QUINCL were compared with those produced by the structurally related 3-(2-chloroethyl)-tetrazinone, mitozolomide, in the OVCAR-3 cell line. METHODS: Macromolecule synthesis was determined by incorporation of 3H-thymidine, 3H-uridine and 3H-leucine into acid-precipitable fractions of OVCAR-3 cell extracts. Maxam-Gilbert sequencing was used to compare the DNA alkylating sites induced by the tetrazepinones, with those created by mitozolomide. Alkaline sucrose-density sedimentation was employed to detect genomic DNA damage. Also, the effects of the tetrazepinones on the cell cycle were determined by univariate flow cytometry. RESULTS: At 3 h post-treatment, mitozolomide appeared as a selective inhibitor of DNA synthesis, while both tetrazepinones inhibited the synthesis of all three macromolecules. At 24 h post-treatment, the inhibition of DNA synthesis was observed to increase in cells treated with mitozolomide, while it decreased in those previously exposed to the tetrazepinones. Also at 24 h post-treatment, mitozolomide induced accumulation of cells in S(late)/G2M at low concentrations and in S-middle at high concentrations. In contrast, at the same recovery time, cells treated with the tetrazepinones accumulated specifically in G2M, the strength of the block being dose-dependent. At an equimolar concentration, the tetrazepinones induced weaker guanine N-7 alkylation than mitozolomide. By 24 h after treatment, cells exposed to the tetrazepinones showed significantly greater DNA fragmentation than those previously treated with mitozolomide. CONCLUSION: In summary, based on (a) their effects on DNA, RNA, protein synthesis and on the cell cycle, (b) their alkylating power and (c) their interactions with DNA, the 3-(2-chloroethyl)tetrazepinones appeared to kill tumor cells by a novel mechanism which may significantly differ from that of their 3-(2-chloroethyl)-tetrazinone counterpart, mitozolomide.

Alkylation↗
PubMed1997

Design and mechanism of action of a novel cytotoxic 1,2,3-triazene-containing heterocycle, 3,5-dimethyl-pyrido-1,2,3,5-tetrazepin-4-one (PYRZ), in the human epithelial ovarian cancer cell line NIH:OVCAR-3 in vitro.

The mechanism of action of the novel heterocycle 3,5-dimethyl-pyrido-1,2,3,5-tetrazepin-4-one (PYRZ), structurally related to temozolomide, was studied in the human ovarian tumour cell line OVCAR-3. Our results showed that, despite its marked structural similarities to temozolomide, PYRZ presents properties that are atypical of 1,2,3-triazene-containing alkylating agents. In a Maxam-Gilbert DNA sequencing assay, PYRZ showed background levels of DNA alkylation, in contrast to temozolomide which strongly alkylated DNA preferentially at guanine residues. At high concentrations, PYRZ inhibited the synthesis of DNA, RNA and protein 3 h after treatment, in contrast to temozolomide which, in previous work, was found to preferentially inhibit DNA synthesis in OVCAR-3 cells. In cells exposed to PYRZ, alkaline sucrose density-gradient centrifugation showed a dose-dependent increase in DNA fragmentation only 12 and 24 h after treatment. PYRZ induced increasing accumulation of cells in late S and G2+M 6-24 h after treatment. This also contrasts with previous work that showed delayed cell cycle arrest induced by temozolomide in OVCAR-3 cells and in the murine leukaemia L1210 cells. Cell-killing kinetics by PYRZ showed a series of sigmoidal dose-response curves with 50-90% cell killing attained as early as 24 h after treatment in the 25-100 microM dose range. (IC50 clonogenic assay 18 microM). The results suggest that the mechanism of cell killing by PYRZ may be different from that of its parent drug temozolomide, and other alkyl-triazene-containing molecules of the same class.

Antineoplastic Agents↗
PubMed1997

Hospitalized patients with community-acquired pneumonia in Hong Kong: a randomized study comparing imipenem/cilastatin and ceftazidime.

The aetiology and outcome of hospitalized patients with moderate to severe community-acquired pneumonia (CAP) were evaluated in 60 adult patients (38 male 22 female, mean age 68.4 years). They were randomized for treatment with either ceftazidime or imipenem/cilastatin intravenously for 7 days. Bacteriological diagnoses were made in 25 cases (41.6%): Streptococcus pneumoniae (5), Haemophilus influenzae (5), Pseudomonas spp. in particular Pseudomonas aeruginosa (8), Staphylococcus aureus (4), Chlamydia spp. (2), Mycobacterium tuberculosis (2) and Moraxella catarrhalis (3); mixed organisms were found in 4 patients. Forty-two patients (70%) responded satisfactorily to the regimens with improvement in sputum purulence cough and dyspnoea scores; there was no difference in response between the two groups. Sixteen patients (26.6%) underwent bronchoscopy on day 4 because of inadequate response to the antibiotics regimens, and 9 of them (15%) required a modification of the initial treatment with addition of erythromycin in 5 patients vancomycin in 1 cloxacillin in 1 and antituberculous drugs in 2. Three out of the 60 patients (5%) died of pulmonary sepsis: the aetiological agents were M. tuberculosis in one, Pseudomonas spp./methicillin-resistant S. aureus in another, but were not identified in the third. We conclude that treatment with either ceftazidime or imipenem/cilastatin was efficacious for moderate to severe CAP in Hong Kong.

Adult↗
PubMed1997

Assisted reproduction technology in Queen Mary Hospital: ten years' experience.

PURPOSE: To review the experience of an assisted reproduction program. DATA SOURCES: Department of Obstetrics and Gynaecology, University of Hong Kong. STUDY SELECTION: Assisted reproduction in a tertiary referral centre. DATA EXTRACTION: Results of assisted reproduction from 1986-1996. RESULTS: In the past ten years, 1561 treatment cycles of in vitro fertilization and embryo transfer (IVF), 257 of gamete intrafallopian transfer (GIFT) and 217 of pronuclear stage tubal transfer (PROST) were initiated. The clinical pregnancy rates per cycle started were 10.8% for IVF, 16.3% for GIFT and 15.7% for PROST. As a result of improvement in ovarian stimulation and embryo culture, the success rate of the program increased in recent years. The pregnancy rate of IVF per embryo transfer was 20.2% in 1995. Embryo cryopreservation program was started in 1992. Since then, 664 cycles of replacement of frozen-thawed embryos were completed with a pregnancy rate of 14.6% per cycle. One hundred and forty-three cycles of assisted fertilization using various techniques, namely partial zona dissection, subzonal sperm injection and intracytoplasmic sperm injection, were performed. The success rate was the highest for the latter technique with a pregnancy rate of 14% per transfer cycle. A prospective randomized control trial on the use of coculture in assisted reproduction had also been done. Results indicated that coculture of embryos with human oviductal cells improved the implantation rate of the embryos. CONCLUSION: Various technique development have been made to improve the success rate of assisted reproduction as well as the quality of treatment of infertility.

Embryo Transfer↗
PubMed1996

Paecilomyces varioti peritonitis in patients on continuous ambulatory peritoneal dialysis.

Paecilomyces varioti infection is a rare cause of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD). We report two patients who developed P varioti peritonitis complicating CAPD. The clinical features and microbiological data of seven other previously reported cases are reviewed. Approximately half of the patients had received multiple antibiotics before the onset of the peritonitis because of either bacterial peritonitis or exit site infection. There was no particular pattern of peritoneal dialysate cell count, which was characteristic in this fungal peritonitis. Although all patients survived, morbidity was high. All patients required antifungal chemotherapy and removal of peritoneal catheter for eradication of the organism. Amphotericin B was effective in most cases. Patients of all previously reported cases did not go back to peritoneal dialysis after removal of peritoneal catheters. A combination of oral flucytosine and itraconazole was successful in treating our two patients. Although we managed to resume CAPD in our two patients with good functional outcome, abscesses and adhesions were major problems rendering most patients from other series failing to return to CAPD after recovery.

Adult↗
PubMed1996

Urinary tract infection caused by Mycobacterium terrae complex.

We describe a case of recurrent urinary tract infection caused by Mycobacterium terrae complex in a patient with obstructive nephropathy. The mycobacterium was resistant to most antituberculosis drugs and despite its apparent clearance in the urine, the patient finally died of urinary sepsis caused by multiple bacterial pathogens.

Aged↗
PubMed1996

Comparisons of Y-set disconnect system (Ultraset) versus conventional spike system in uremic patients on CAPD: outcome and cost analysis.

We conducted a single-blind, prospective randomized study on the use of the Y-set disconnect system (Ultraset) (U) versus the conventional (C) spike system to assess the peritonitis rate, exit-site infection (ESI), clinical outcome, the resulting hospitalization rate, and recurrent costs. Forty new end-stage renal failure patients admitted to the dialysis program were recruited into the study and 20 each were randomly allocated to the U and C systems. They were studied for a period of 12 months. The mean number of days required to train patients for the U and C systems were 8.6 and 9.8 days, respectively. The peritonitis rates for the U and C systems were one episode every 17 and 11.4 patient-months, respectively. The ESI rates for the U and C systems were one episode every 26.4 and 21.6 patient-months, respectively. Four catheters were removed due to fungal peritonitis (three with the C system and one with the U system). As related to peritonitis, patients on the C system required 57 hospital-days while those on the U system required 28 days per year. On cost analysis, the extra cost required for the U system can be offset by the other expenses incurred for events related to more infections on the C system. It is concluded that for the similar cumulative costs required for the patients on the two systems, the Y-set disconnect has a better morbidity profile than the conventional spike system.

Adult↗
PubMed1995

Effect of fluvastatin on lipoprotein profiles in treating renal transplant recipients with dyslipoproteinemia.

A single, blinded placebo-drug trial was conducted to study the efficacy and safety of fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in treating dyslipoproteinemia in 16 renal transplant recipients who had been on an immunosuppressive regimen that included cyclosporine (CsA). They were studied for 32 consecutive weeks, with 4 weeks of baseline treatment, 4 weeks of placebo, 12 weeks of treatment with fluvastatin 20 mg daily, and 12 weeks of fluvastatin 40 mg daily. Blood samples were obtained every 4 weeks for measurement of the lipoprotein profiles, which included total cholesterol (TC), triglyceride, low density lipoprotein (LDL)-, high density lipoprotein (HDL)-, HDL2-, HDL3- and very low density lipoprotein-cholesterol (C), apolipoprotein (Apo) A-1, Apo B, and lipoprotein(a). Fifteen patients completed the trial. After 12 weeks of treatment, fluvastatin 20 mg significantly reduced TC by 13.4% (from 6.7 +/- 0.5 [mean +/- SEM] to 5.8 +/- 0.2 mmol/L), LDL-C by 22% (from 4.1 +/- 0.3 to 3.2 +/- 0.2 mmol/L), and Apo B by 13.2% (from 159.6 +/- 8.8 to 138.6 +/- 9.2 mg/dl) (P < 0.005). The subsequent 12-week treatment of fluvastatin 40 mg significantly reduced TC by 16.4% to 5.6 +/- 0.3 mmol/L, LDL-C by 29.3% to 2.9 +/- 0.2 mmol/L, and Apo B by 18.2% to 130.6 +/- 5.5 mg/dl (P < 0.00005). There was no significant change in levels of other lipoproteins, including lipoprotein (a). There were no significant changes in the whole blood trough CsA concentrations, renal and liver function tests, and serum creatine phosphokinase level during treatment when compared with baseline and placebo. No patient complained of myalgia or failed to complete the study due to side effects of the drug. Fluvastatin appears to be safe and effective in treating dyslipoproteinemia in renal transplant recipients who are maintained on CsA.

Adult↗
PubMed1995

Molecular genetics of major histocompatibility complex class II genes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver with a possible genetic predisposition. We have studied the HLA-DQ and -DR regions of 57 unrelated HCC patients of southern Chinese origin using molecular DNA techniques and compared them with 104 normal controls. Seventy-six hepatitis B carriers (HBsAg) were also studied. Restriction fragment length polymorphism (RFLP) was used to genotype the MHC class II DR beta, DQ alpha and DQ beta loci of the subjects. Polymerase chain reaction (PCR) using sequence primer for DQ beta genes was also performed. No significant difference was found in the HLA-DQ and -DR loci between HCC patients and normal controls, HCC patients and HBsAg carriers, or HBsAg carriers and normal controls respectively. Forty-one HCC patients were HBsAg positive, and no difference was found in the HLA-DQ and -DR genotype between this group of patients compared with the group of normal controls or HBsAg carriers. Thirty-six HCC patients had elevated alpha-fetoprotein levels, and 15 HCC patients had normal levels. No difference in the HLA-DQ and -DR loci was detected between these two groups and the controls. The results suggest that HLA-DQ and -DR genotypes are not associated with hepatocellular carcinoma in southern Chinese.

Carcinoma, Hepatocellular↗