Evaluating a medical day center in Hong Kong. Evidence-based management practice.
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Day Care, Medical↗
Biomedical subjects
V Chan
Publications and source records attributed to V Chan.
Characterization of a new member of the TNF family expressed on antigen presenting cells.
The TNF family is involved in the regulation of the immune system, and its members have been implicated in a variety of biological events such as apoptosis, cell proliferation, differentiation and survival. Here we present a new member of the TNF family, tumor necrosis factor superfamily member 20 (TNFSF20) that we have identified from the expressed sequence tag (EST) database and characterized. The human protein is a 285 amino acid long type II transmembrane protein and is 19% homologous to TNF in its extra-cellular domain. TNFSF20 is expressed at the surface of antigen presenting cells such as cells of the macrophagemonocyte lineage and dendritic cells. After treatment with bacterial lipopolysaccharide (LPS), TNFSF20 expression is downregulated at the surface of the expresssing cells, suggesting that the membrane-bound protein gets cleaved, and that a soluble factor is released in the extra-cellular compartment. The soluble form of the recombinant TNFSF20 induces proliferation of resting peripheral blood monocytes (PBMC) and cell death of activated lymphocytes. TNFSF20 might therefore play a critical role in the regulation of cell-mediated immune responses.
Amino Acid Sequence↗
Genetic analysis of adenovirus E1A: induction of genetic instability and altered cell morphologic and growth characteristics are segregatable functions.
Single multifunctional oncoproteins contribute to genomic instability development, but relationships between one or more oncoprotein-associated activities and genetic changes accompanying tumor cell progression are uncertain. Using NIH 3T3 derivative EN/NIH 2-20 containing transcriptionally silent neomycin phosphotransferase gene (neo) integrants with undetectable spontaneous reactivations, we studied wild-type (WT) and mutant adenovirus E1A-induced neo reactivation by neo-allelic rearrangement. WT E1A expression, yielding differential splice transcripts 12S and 13S and resulting in altered cell morphologic and growth characteristics, produced neo reactivations in 9 of 21 subclones (median rate per cell, 35 x 10(-6); range, 0.33 x 10(-6) to 936 x 10(-6)). Only 3 of 17 cell lines expressing CTdl976, a '12S' functional equivalent inducing altered cell morphologic and growth characteristics while lacking the 13S trans activation domain, yielded neo reactivations (range, 0.33 x 10(-6) to 0.67 x 10(-6)). One of 21 subclones expressing NTdl646, an E1A mutant retaining the trans domain but lacking p300 binding activity and the ability to alter cell morphologic and growth characteristics, produced neo reactivations (8.7 x 10(-6)). Other E1A mutants, all lacking the ability to alter cell morphologic and growth characteristics while binding pRb but variously lacking the trans domain and binding for p107 and/or p300, displayed undetectable neo-reactivations. 98 EN/NIH 2-20 derivatives coexpressing complementary mutant E1As exhibited altered morphologic and growth features, but only 10 of these produced neo reactivations, and maximum rates (14 x 10(-6)) were substantially lower than those in comparably derived, morphologically altered E1AWT-expressing counterparts (497 x 10(-6)). These findings suggest that maximum rates of gene reactivations by genomic rearrangement require the collective activities of functional domains assembled in single multifunctional proteins (or complexes) while altered cell morphologic and growth characteristics may arise through comparable sets of functional domains distributed across more than one protein (or complex).
3T3 Cells↗
Diagnosis of spinal muscular atrophy from fetal normoblasts in maternal blood.
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DNA Primers↗
Hemosiderosis with diabetes mellitus in untransfused Hemoglobin H disease.
A 37-year-old untransfused, non-drinking man with Hemoglobin H-CS disease presented with insulin-dependent diabetes mellitus, markedly elevated serum ferritin level, and marked iron deposition in hepatocytes. He did not carry either of the two common mutations of the HLA-H gene for hereditary hemochromatosis, namely, Cys282Tyr and His68Asp, nor did he have the associated HLA marker (HLA-A3, B7 nor B-14) for the disease. Patient with HbH disease should be monitored for iron overload.
Adult↗
Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome.
A novel missense mutation (codon 351, GCT (Ala) --> CCT (Pro)) of the FIX gene was characterised in a young female with mild hemophilia B. She is heterozygous for the FIX mutation inherited from her carrier mother. Analysis of the methyl-sensitive Hpa II sites at the 5' end of the hypoxanthine phosphoribosyltransferase gene showed that skewed inactivation of the X chromosome carrying her normal FIX gene accounted for the hemophilia phenotype.
Adult↗
Pharmacokinetics of three doses of epidural ropivacaine during hysterectomy and comparison with bupivacaine.
PURPOSE: Ropivacaine is a new long-acting aminoamide local anaesthetic, structurally related to bupivacaine. The clinical efficacy of 125 mg, 187.5 mg and 250 mg ropivacaine have been reported and compared with 125 mg bupivacaine for epidural analgesia during hysterectomy. In the pharmacokinetic part of this study the objectives were to 1) determine the dose proportionality in the pharmacokinetics of epidural ropivacaine, and 2) compare the pharmacokinetics of 125 mg ropivacaine and 125 mg bupivacaine. METHODS: In a randomized, double-blind controlled study, patients received one of four treatment regimens with ropivacaine (125, 187.5 or 250 mg) or bupivacaine (125 mg) as a 25 ml epidural bolus administered over three minutes. Peripheral venous blood samples were collected over 24 hr for ropivacaine or bupivacaine quantification using gas chromatography with nitrogen sensitive detection. Pharmacokinetic variables were derived from plasma concentration-time curve data. RESULTS: Fifty two women entered the study. Demographic characteristics were similar among groups. Six patients were excluded due to inadequate sensory block or an insufficient number of plasma samples. The peak plasma concentration (Cmax) of ropivacaine and the total area under the plasma concentration-time curve (AUC) increased proportionally with the dose. Apparent plasma clearance (CL) and the terminal half-life (t1/2) were similar in the three ropivacaine groups. When compared with the 125 mg ropivacaine group, the bupivacaine group had a longer terminal half life (P < 0.05). CONCLUSIONS: Epidural ropivacaine displays dose-proportional pharmacokinetic behaviour for doses of 125 mg to 250 mg. Ropivacaine has a shorter terminal half-life than bupivacaine.
Adult↗
Advances in regional anaesthesia and pain management.
Advances in regional anaesthesia to date have made it one of the safest modalities for surgical anaesthesia and pain management. Continued refinement and development of new block techniques and approaches enhance the potential for block success, rapid postoperative recovery and patient safety. This will benefit both patient care and the health care economy.
Amides↗
Sequence effect of irinotecan (CPT-11) and topoisomerase II inhibitors in vivo.
UNLABELLED: The DNA topoisomerases I and II are the target of several clinically important antineoplastic agents which produce DNA cleavage by stabilization of the covalent DNA-protein bond with resultant cell death after DNA synthesis is attempted. Depletion of the target topoisomerase and reciprocal changes in the other occur with drug treatment. PURPOSE AND METHODS: To develop empiric treatment regimens of combinations and sequences of agents directed against topoisomerase I (irinotecan/CPT-11) and II (etoposide and doxorubicin), in vivo studies were performed in mice bearing the EMT-6 mammary tumor to assess efficacy, host tolerance and the resultant biochemical changes in topoisomerase mRNA and protein. RESULTS: At 24 h after therapy, depletion of the target topoisomerase mRNA and protein with reciprocal increases in the alternate topoisomerase mRNA and, to a lesser extent, protein were noted. No therapeutic antagonism was found with any combination or sequence of agents, and therapeutic antagonism was noted with concurrent irinotecan/etoposide and sequential doxorubicin/irinotecan. Depletion of target topoisomerases by combined therapy beyond a threshold necessary for therapeutic efficacy produced no additional benefit. CONCLUSIONS: Antineoplastic therapy with combinations of topoisomerase I and II agents is feasible and may produce therapeutic synergy. The appropriate sequence may depend on the particular agents used. The rationale for such therapy, that topoisomerases I and II may have reciprocal and compensatory interactions, is supported by the biochemical data.
Animals↗
Molecular defects in Hb H hydrops fetalis.
The molecular defect in two unique cases of Hb H hydrops fetalis has been characterized. Both cases are due to co-inheritance of a 'non-deletion' defect affecting the alpha2 gene: at codon 30 delta GAG, Glu) and codon 59 (G --> A, Gly --> Asp) respectively, and a zeta-alpha thalassaemia (thal) 1 or alpha thal 1 genotype. These two non-deletion defects, unlike previously described cases, resulted in severe anaemia of the fetuses and emphasize the importance of performing prenatal diagnosis for these families.
Gene Deletion↗
The addition of continuous intravenous infusion of ketorolac to a patient-controlled analgetic morphine regime reduced postoperative myocardial ischemia in patients undergoing elective total hip or knee arthroplasty.
This double-blind randomized trial assessed the effect of adding an intravenous continuous infusion of ketorolac to a patient-controlled analgesia (PCA) morphine regimen on analgesia, heart rate, arterial blood pressure, and postoperative myocardial ischemia. Patients having elective total hip or knee replacement were randomized to receive ketorolac 30 mg bolus, followed by an infusion of 5 mg/h for 24 h or placebo. All patients had access to PCA morphine (20 microg/kg bolus, with a lockout of 6 min). Patients were monitored for pain visual analog scale, blood pressure, heart rate, and ST segment depression via a continuous Holter monitor. ST depression of 1 mm 60 ms after the J point was considered significant if it lasted more than 1 min. There was no difference in demographics, risk factors, or cardiac medications between the groups. Ketorolac-treated patients had significantly better pain control at 2, 6, and 24 h. There was significant morphine sparing at all times after 3 h. There was no difference in the number of ischemic events between the groups. The ischemic episodes of the patients who received ketorolac occurred at slower heart rates (97 +/- 15 vs 114 +/- 16 bpm, P = 0.001) than those of patients in the placebo group. The duration of ST depression was shorter in ketorolac-treated patients (24 +/- 35 vs 76 +/- 95 min, P < 0.05). All ST depressions were clinically silent. Logistic regression of factors predicting ischemia included the use of calcium channel blockers and low pain score. These results suggest that analgesia with ketorolac reduces the duration of ischemic episodes in the first 24 h postoperatively.
Aged↗
Molecular detection of minimal residual disease for patients with leukaemia and lymphoma.
Although a complete clinical remission can often be achieved with chemotherapy for patients with leukaemia and lymphoma, relapses still occur. Residual tumour cells probably have survived therapy and account for subsequent disease relapse. The sensitivity of conventioned ways of detecting residual tumour cells, such as morphological studies, immunophenotyping, and cytogenetics, is only about 1% to 5% and may be inadequate. Polymerase chain reaction technology has provided a simple and highly sensitive means for the detection of minimal residual disease. The technology has been successfully applied to study biopsy samples obtained from patients with leukaemia and lymphpma. Its clinical usefulness, however, requires further evaluation by prospective clinical studies.
Journal Article↗
Detection of T-cell receptor delta gene rearrangement by clonal specific polymerase chain reaction.
A sensitive and specific technique to detect minimal residual disease for T-cell malignancies was explored. Southern analysis and polymerase chain reaction (PCR) were used to detect the rearranged V-D-J segment of T-cell receptor delta (TCR delta) gene from malignant cell specimens of patients with leukemia and lymphoma of T-cell lineage. The PCR product was sequenced and from the DNA sequences of the V-D-J region, a 3' antisense primer was designed and synthesized for clonal specific PCR (CS-PCR). Seven of the 22 T-ALL (32%) and 5 of 18 (28%) T-cell lymphoma showed clonal rearrangement by Southern analysis. Six of the 7 (86%) T-ALL and 4 of the 5 (80%) T-cell lymphoma which were Southern positive were also positive by TCR delta PCR. The PCR products of four cases of T-ALL showing clonal pattern by TCR delta PCR amplification were successfully sequenced and CS-PCR amplification performed. CS-PCR detected with confidence specific clonal rearrangement in a mixture containing 0.003% of malignant cells. Marrow specimens obtained at diagnosis and subsequent follow-ups from the 4 T-ALL patients were studied by Southern analysis, TCR delta PCR and CS-PCR. The first patient was in continuous morphological complete remission for more than 3 years and had persistently negative Southern, TCR delta PCR and CS-PCR results on follow-up. Initial follow-up marrow samples from the second patient had persistently positive CS-PCR results while they were still morphologically and TCR delta PCR negative and the patient had a frank leukemic relapse at 18 months. The other two patients had persistent disease by conventional morphological examination, Southern analysis, TCR delta PCR and CS-PCR studies were all positive as expected. CS-PCR is a highly specific and sensitive technique in detecting minimal residual disease for T-cell malignancies. Its potential applications warrant further clinical evaluation and correlation.
Base Sequence↗
The risk of alpha-thalassaemia in offspring of beta-thalassaemia carriers in Hong Kong.
Couples in whom one is heterozygous for alpha-thalassaemia-1 and the other is heterozygous for beta-thalassaemia are assumed not to be at risk of having offspring with homozygous alpha-thalassaemia-1 or homozygous beta-thalassaemia. We retrospectively reviewed the genetic outcome of 189 pregnancies of 178 couples in whom the partners were diagnosed to be discordant heterozygotes of alpha-thalassaemia and beta-thalassaemia on haematological tests. Zeta gene mapping was performed on 158 beta-thalassaemia carriers to diagnose the presence of co-existing alpha-thalassaemia-1. Eleven patients (7 per cent) were found to be compound alpha- and beta-thalassaemia heterozygotes. They accounted for 16 pregnancies, of which five were diagnosed to be affected by homozygous alpha-thalassaemia-1. Our results show that couples presumed to be discordant heterozygotes of alpha- and beta-thalassaemia on haematological testing are at risk of having offspring with homozygous alpha-thalassaemia-1 if the zeta gene mapping of the heterozygous beta-thalassaemia partner shows co-inheritance of alpha-thalassaemia-1. Prenatal diagnosis of homozygous alpha-thalassaemia-1 should be performed on these at-risk pregnancies.
Chromosome Mapping↗
Alpha and beta thalassemias in Hong Kong.
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Female↗
Essential thrombocythemia with BCR/ABL rearrangement.
Essential thrombocythemia (ET) was diagnosed clinically in three patients Karyotypic analysis and reverse transcription polymerase chain reaction for the bcr-abl chimeric transcript showed that two were Philadelphia chromosome (Ph) positive, bcr-abl positive, whereas the third was Ph negative, bcr-abl positive. The first patient received an allogeneic bone marrow transplantation but relapsed as localized blastic transformation, thus behaving similarly to chronic myeloid leukemia (CML). However, the other patients showed clinical courses more in keeping with ET. Essential thrombocythemia with BCR rearrangements may resemble CML but there are clinical differences. These may be due to genetic changes in addition to the BCR rearrangement.
Adult↗
Detection of T-cell receptor delta gene rearrangement in T-cell malignancies by clonal specific polymerase chain reaction and its application to detect minimal residual disease.
A clonal-specific polymerase chain reaction technique to detect T-cell receptor delta gene rearrangement in acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL) was evaluated. It was applied to detect minimal residual disease. A sensitive and specific technique to detect minimal residual disease for T-cell malignancies was explored. Southern analysis and polymerase chain reaction (PCR) were used to detect the rearranged V-D-J segment of T-cell receptor delta (TCR delta) gene from malignant cell specimens of patients with leukemia and lymphoma of T-cell lineage. The PCR product was sequenced and from the DNA sequences of the V-D-J region, a 3' anti-sense primer was designed and synthesized for clonal specific PCR (CS-PCR). T-cell receptor delta (TCR-delta) gene rearrangement was studied in 40 cases of acute leukaemia and lymphoma of T-cell lineage at diagnosis. Using Southern analysis, the positive rates were 28 and 32% for the 18 T-lymphoma and 22 T-ALL, respectively. A one stage Polymerase Chain Reaction (PCR) technique was used to detect the rearrangement in Southern positive cases and the PCR positive rates were 80 and 86%, respectively. The PCR technique had a sensitivity of 0.1%. Serial follow-up marrow specimens were available from 4 T-ALL patients following chemotherapy for monitoring of minimal residual disease. Their PCR products were DNA sequenced. A 3' primer was designed for each case for a clonal specific (CS) PCR. The technique had a sensitivity of 0.003%. It was applied to detect minimal residual disease in serial follow-up marrow samples. The first patient had persistent negative CS-PCR results and enjoyed continuous remission for more than 3 years. The second patient with negative one stage PCR but positive CS-PCR results had eventual relapse of leukaemia. The other two patients never achieved a morphological remission. These preliminary results appeared to support the usefulness of these PCR techniques in detecting minimal residual disease and predicting relapses for ALL. However, further clinical correlation in larger populations of patients is necessary.
Base Sequence↗
A double-blind comparison of ropivacaine 0.5%, 0.75%, 1.0% and bupivacaine 0.5%, injected epidurally, in patients undergoing abdominal hysterectomy.
PURPOSE: Ropivacaine is a new long-acting, injectable local anaesthetic currently undergoing clinical investigation world wide. It is structurally very similar to bupivacaine, but with less potential for central nervous system or cardiac toxicity. The purpose of this double-blind study was: to investigate the dose-response relationship of increasing doses of ropivacaine on the quality of anaesthesia and the duration of both motor and sensory blockade, and to compare these results with an established local anaesthetic, bupivacaine. METHODS: One hundred and twenty five patients were randomly assigned to one of four treatment groups and 116 completed the study. Epidural anaesthesia was established using 25 ml test solution, injected over three minutes following a satisfactory test dose. Sensory onset, spread and duration, using the pin prick method, and motor scores using a modified Bromage scoring system were compared. RESULTS: A dose/response relationship was observed with increasing doses of ropivacaine for all variables tested except analgesia and muscle relaxation (P < 0.01). There were differences in: (i) motor onset (Levels 1 and 2), when ropivacaine 1.0% was compared with ropivacaine 0.75% and 0.5% (P < 0.05); (ii) in sensory duration at all levels except T6 when ropivacaine was compared with ropivacaine 0.5% (P < 0.05); (iii) differences in sensory duration at T12 and S1 when ropivacaine 1.0% was compared with bupivacaine 0.5% (P < 0.05); (iv) differences in motor duration at all levels when ropivacaine 1.0% was compared with ropivacaine 0.5% (P < 0.05). No serious adverse events were reported in this study. CONCLUSION: Increasing doses of ropivacaine were associated with an increased clinical effect. The most consistent differences occurred when ropivacaine 1.0% was compared with 0.5% and the least consistent between ropivacaine 0.5%, 0.75% and bupivacaine 0.5%. The main difference between ropivacaine 1.0% and bupivacaine was in sensory duration. No serious adverse events were reported.
Adolescent↗