Introducing the Skills Development Centre of the Department of Surgery, University of Hong Kong.
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Education, Medical, Continuing↗
Biomedical subjects
J Chan
Publications and source records attributed to J Chan.
Paediatric liver transplantation: Queen Mary Hospital experience.
OBJECTIVE: To assess the results of paediatric liver transplantation in our institution. METHODS: From September 1993 to November 1996, 10 living-related liver transplants (LRLT) and 3 reduced-size liver transplants (RSLT) were performed on 12 children at our hospital. The medical records of the patients were reviewed. All patients suffered from end-stage liver disease resulting from biliary atresia with failed Kasai's operations. Their ages at initial transplantation ranged from 8 months to 11 years. Excluding the 2 older children aged 7.5 and 11 years, the remaining patients were aged 10.5 months on the average and weighed 6 to 9.5 kg (mean: 6.8 kg) at the time of initial transplantation. RESULTS: All living donors were discharged on postoperative day 4 to 8 and resumed their previous normal activities. All recipients were alive with normal liver function and growing after a follow-up period of 3-40 months (mean: 21 months). The patient survival rate was 100%. One patient with RSLT had hepatitis of undetermined aetiology and underwent retransplant with a graft from her mother. The graft survival rate was 92%. Postoperative complications included: postoperative bleeding (n = 3), hepatic vein stenosis (n = I), biliary-enteric anastomotic stenosis (n = 3), intestinal perforation (n = I) and portal vein thrombosis (n = I). They were all treated promptly. In all patients, the hepatic artery (diameter ranged from 1.5 to 2.5 mm) anastomosis was achieved by microvascular technique. There was no hepatic artery thrombosis in our patients. CONCLUSION: With technical refinements, early detection and prompt treatment of complications, and advances in immunotherapy, excellent results can be achieved in paediatric liver transplantation.
Biliary Atresia↗
Deep vein thrombosis and pulmonary embolism in the Chinese population.
Deep vein thrombosis and pulmonary embolism is a well-recognised major health problem in the West. There is a deep-rooted belief among clinicians that deep vein thrombosis is rare in Asians, particularly in the Chinese population. However, it appears that the incidence of venous thrombosis and pulmonary embolism is increasing in Chinese patients. Prophylaxis reduces the incidence of venous thrombosis by 66% and of pulmonary embolism by 50%--- prophylaxis should therefore be considered for Chinese patients who have a high risk of developing postoperative deep vein thrombosis. This report reviews the current literature on this subject.
Journal Article↗
Evidence-based medical practice: ethical considerations.
The practice of medicine according to ethical principles requires that decisions regarding treatment, preventive or interventional strategies, or quality of life of patients in relation to life-support treatment should be based on evidence as far as possible. Available evidence for Hong Kong is reviewed under the following categories: use of drugs, management strategies, service provision, and interventions to prevent disease and/or disability. These examples highlight the need for studies to obtain evidence in the local population, as findings from studies in other countries may not be applicable. Although evidence exists in many areas to guide practice, the biggest challenge is how to implement such practice to ensure equitable access to prevention and treatment, particularly in the presence of health care resource limitations.
Journal Article↗
The dopamine transporter: comparative ultrastructure of dopaminergic axons in limbic and motor compartments of the nucleus accumbens.
The dopamine transporter (DAT) regulates extracellular dopamine concentrations, transports neurotoxins, and acts as a substrate for cocaine reinforcement. These functions are known to differ in the limbic-associated shell and motor-associated core compartments of the nucleus accumbens (NAc). Previous studies have shown differential expression of DAT in the NAc shell and core but were limited in resolution to the regional level. Thus, it is not known whether there are differences in the amount, subcellular localization, or plasmalemmal targeting of DAT within individual dopaminergic axons in the two regions. We used high-resolution electron microscopic immunocytochemistry to investigate these possibilities. We show that in both the shell and core, DAT immunogold labeling is present in tyrosine hydroxylase-immunoreactive varicose axons that form symmetric synapses. Within these labeled axons, most DAT gold particles are located on extrasynaptic plasma membranes, but some are associated with intracellular membranes. Dopaminergic axons in the shell contain lower mean densities of both total DAT gold particles (per square micron) and plasmalemmal DAT gold particles (per micron) than those in the core. Within labeled axons in the NAc shell and core, however, there are no detectable differences in the subcellullar distribution of DAT or the percentage of total DAT gold particles that are located on plasma membranes. These studies are the first to examine and compare the subcellular localization of DAT in the NAc shell and core. As a result, they identify intrinsic, cell-specific differences in the expression of DAT within dopaminergic axons in these functionally distinct striatal compartments.
Animals↗
Immunogold localization of the dopamine transporter: an ultrastructural study of the rat ventral tegmental area.
The dopamine transporter (DAT) plays an important role in the plasmalemmal reuptake of dopamine and, thus, in the termination of normal dopaminergic neurotransmission. DAT is also a major binding site for cocaine and other stimulants, the psychoactive effects of which are associated primarily with the inhibition of dopamine reuptake within mesocorticolimbic dopaminergic neurons. We used electron microscopy with an anti-peptide antiserum directed against the N-terminal domain of DAT to determine the subcellular localization of this transporter in the rat ventral tegmental area (VTA), the region that contains the cell bodies and dendrites of these dopaminergic neurons. We show that in the VTA, almost 95% of the DAT immunogold-labeled profiles are neuronal perikarya and dendrites, and the remainder are unmyelinated axons. Within perikarya and large proximal dendrites, almost all of the DAT immunogold particles are associated with intracellular membranes, including saccules of Golgi and cytoplasmic tubulovesicles. In contrast, within medium- to small-diameter dendrites and unmyelinated axons, most of the DAT gold particles are located on plasma membranes. In dually labeled tissue, peroxidase reaction product for the catecholamine-synthesizing enzyme tyrosine hydroxylase is present in DAT-immunoreactive profiles. These findings suggest that intermediate and distal dendrites are both the primary sites of dopamine reuptake and the principal targets of cocaine and related psychostimulants within dopaminergic neurons in the VTA.
Animals↗
Immunogold localization of the dopamine transporter: an ultrastructural study of the rat ventral tegmental area.
The dopamine transporter (DAT) plays an important role in the plasmalemmal reuptake of dopamine and, thus, in the termination of normal dopaminergic neurotransmission. DAT is also a major binding site for cocaine and other stimulants, the psychoactive effects of which are associated primarily with the inhibition of dopamine reuptake within mesocorticolimbic dopaminergic neurons. We used electron microscopy with an anti-peptide antiserum directed against the N-terminal domain of DAT to determine the subcellular localization of this transporter in the rat ventral tegmental area (VTA), the region that contains the cell bodies and dendrites of these dopaminergic neurons. We show that in the VTA, almost 95% of the DAT immunogold-labeled profiles are neuronal perikarya and dendrites, and the remainder are unmyelinated axons. Within perikarya and large proximal dendrites, almost all of the DAT immunogold particles are associated with intracellular membranes, including saccules of Golgi and cytoplasmic tubulovesicles. In contrast, within medium- to small-diameter dendrites and unmyelinated axons, most of the DAT gold particles are located on plasma membranes. In dually labeled tissue, peroxidase reaction product for the catecholamine-synthesizing enzyme tyrosine hydroxylase is present in DAT-immunoreactive profiles. These findings suggest that intermediate and distal dendrites are both the primary sites of dopamine reuptake and the principal targets of cocaine and related psychostimulants within dopaminergic neurons in the VTA.
Animals↗
A 60-kDa plant microtubule-associated protein promotes the growth and stabilization of neurotubules in vitro.
The search for microtubule-associated proteins (MAPs) in plants is relatively recent. In particular, the "classical MAPs," which stimulate the polymerization and stabilization of microtubules, have only been examined in heterogeneous fractions. As a first step in dissecting the role of individual MAPs, we have chromatographically purified a single 60-kDa protein from a carrot MAP fraction and analyzed its effects on tubulin assembly. MAP60 promoted the formation of long, morphologically regular brain microtubules in vitro, an effect inhibited by preincubation of the MAP with affinity-purified antibodies against this protein. MAP60 also increased the stability of microtubules to dilution and significantly enhanced cold stability to the normally cold-sensitive neurotubules. These in vitro properties are consistent with a role for MAP60 in regulating the turnover/assembly of dynamic plant microtubules in vivo.
Animals↗
Electron microscopic evidence for coexistence of leucine5-enkephalin and gamma-aminobutyric acid in a subpopulation of axon terminals in the rat locus coeruleus region.
We recently described ultrastructural evidence for morphologically heterogeneous axon terminals containing the endogenous opioid peptide, methionine5-enkephalin (ENK), that formed synapses with neurons containing the catecholamine synthesizing enzyme, tyrosine hydroxylase, in the locus coeruleus (LC) of the rat brain. The morphological characteristics of these terminals suggested that ENK may be co-localized with either an excitatory or inhibitory amino acid. To further test this hypothesis, we combined immunogold-silver localization of gamma-aminobutyric acid (GABA) and immunoperoxidase labeling for ENK in single sections through the LC, in the present study, to determine whether ENK and GABA were contained within single axon terminals. Light microscopic analysis of ENK and GABA immunoreactivities in the LC indicated that both transmitters were enriched in the dorsal pons. Although electron microscopy revealed that ENK and GABA were located primarily in axon terminals, some dendrites also contained immunolabeling for GABA. The dense core vesicles were consistently the most immunoreactive in ENK containing axon terminals and were identified toward the periphery of the axon terminal distal to the synaptic specialization. Axon terminals containing either ENK or GABA immunoreactivities contained pleomorphic vesicles as well as large dense core vesicles, varied in size and formed heterogeneous types of synaptic specializations (i.e. asymmetric vs. symmetric). Approximately 38% (n = 76) of the axon terminals containing ENK immunoreactivity (n = 200) also contained GABA. Some axon terminals containing peroxidase labeling for ENK (22%; n = 44) converged on common targets with GABA-labeled axon terminals. Finally, a few ENK-labeled axon terminals (14%; n = 28) formed asymmetric (excitatory-type) synapses with dendrites containing gold-silver labeling for GABA. The results, therefore, indicate that the opioid peptide, ENK, and the inhibitory amino acid, GABA, may influence LC neurons by concerted actions via (1) release from a common axon terminal, and (2) via separate sets of afferents converging on similar portions of the plasmalemma of target neurons. Furthermore, these studies also suggest a cellular substrate for opioid inhibition of LC neurons via activation (i.e. asymmetric synapses) of inhibitory GABAergic neurons. Future studies are required to determine whether the receptive sites for ENK and GABA are located at similar sites on the plasma membranes of LC neurons pre- or postsynaptically and whether there is differential release of either transmitter from single terminals in the LC.
Animals↗
Vesicular monoamine transporter-2: immunogold localization in striatal axons and terminals.
The vesicular monoamine transporter-2 (VMAT2) mediates the reserpine-sensitive neuronal uptake of monoamines into vesicles and other intracellular organelles. Accordingly, this transporter is expressed at high levels in regions that contain a dense monoamine innervation, such as the rat dorsolateral striatum. We used ultrastructural immunocytochemistry in this region to show that immunogold labeling for VMAT2 is present in varicose axonal processes, many of which also contain the catecholamine-synthesizing enzyme tyrosine-hydroxylase. Within these mainly dopaminergic processes, VMAT2 was associated with small synaptic vesicles (SSVs) and more rarely with large dense-core vesicles or tubulovesicles. These findings suggest that SSVs are the major organelles involved in the storage and release of dopamine in the dorsolateral striatum.
Animals↗
Intraepidermal nerve fiber expression of calcitonin gene-related peptide, vasoactive intestinal peptide and substance P in psoriasis.
In order to evaluate more fully the role of neuropeptides in the pathogenesis of psoriasis, skin biopsies were obtained from 36 patients with psoriasis to identify substance P (SP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP). Lesional and nonlesional skin was examined from these biopsies and the results compared with those from biopsies taken from patients with a variety of other inflammatory dermatoses, including lichen planus, lichen simplex chronicus, spongiotic dermatitis, and seborrheic dermatitis. Also studied was a series of nine biopsies taken from patients with no known skin disorders. We found an increase in the number of SP-positive nerve fibers within the epidermis in biopsies from lesional skin of psoriasis patients (8.4 nerves per 3-mm biopsy) compared with nonlesional psoriatic skin (2.6 nerves per 3-mm biopsy) and normal skin (2.0 nerves per 3 mm biopsy). Other inflammatory disorders also demonstrated fewer SP-positive nerves than lesional psoriatic skin; lichen planus (0 nerves per 3 mm biopsy) and lichen simplex chronicus (1.3 nerves per 3 mm biopsy). The difference in SP-positive nerve expression between lesional psoriatic skin and the group comprising nonlesional skin, normal skin, lichen planus, and lichen simplex chronicus attained statistical significance (P < 0.013). SP-positive intraepidermal nerve fibers in lesional psoriatic specimens were fewer than in spongiotic dermatitis (17.4 nerves per 3 mm biopsy). There was no significant difference in numbers of VIP- or CGRP-immunopositive intraepidermal nerve fibers between psoriatic skin and the group comprising all other material tested. However, in five patients with psoriasis, there was a marked increase in the expression of intraepidermal CGRP (up to 10.7 nerves per 3-mm biopsy) and VIP (up to 8.3 nerves per 3-mm biopsy) which was not observed in control groups. These findings suggest that neuropeptides SP, CGRP, and VIP play a role in the pathogenesis of psoriasis.
Adult↗
Liver transplantation in children: the experience of Queen Mary Hospital, Hong Kong.
Seven living-related liver transplants (LRLT) and two reduced-size liver transplants (RSLT) were performed on eight children who suffered from end-stage liver disease, having previously undergone one to three abdominal operations. Their ages at initial transplantation ranged from 8 months to 11 years (mean 35 months, median 12 months). Excluding the two older children aged 7 and 11 years, respectively, the rest of the children weighed 6 to 9.5 kg (mean 7.3 kg) at the time of the initial transplantation. Seven left lateral segments (S2 + 3) and two left lobes (S2 + 3 + 4) were used; of these the smallest graft had a graft-to-recipient body weight ratio of 0.9%. The volunteer living donors were four mothers, two fathers and one sister who were selected after medical and psychiatric evaluations, and their suitability was confirmed by hematological, biochemical, and radiological criteria. During a follow-up period of 3 to 30 months, all eight children are alive and well with normal liver function, one of them having undergone a retransplant LRLT because of hepatitis of undetermined etiology following a RSLT 1.5 years earlier. All seven donors had an uneventful postoperative course and were discharged on day 4 to 7 postoperatively. They have all resumed normal day-to-day activities. There were no complications in the donor group. A variety of complications occurred in the recipients, all of which were overcome. Operating microscope was used to perform all the arterial anastomoses using microvascular techniques. This method has proven to be a major factor in preventing arterial thrombosis even with the smallest of arterial anastomosis where a 1.5-mm diameter recipient artery was anastomosed to a 2.5-mm diameter donor hepatic artery.
Activities of Daily Living↗
Methadone maintenance and drug-related crime.
Using data from an evaluation of methadone maintenance treatment, this study investigated factors associated with continued involvement in crime during treatment, and in particular whether there appeared to be differences in effectiveness of treatment between different methadone clinics. The methodology was an observational study, in which 304 patients attending three low-intervention, private methadone clinics in Sydney were interviewed on three occasions over a twelve month period. Outcome measures were self-reported criminal activity and police department records of convictions. By self-report, crime dropped promptly and substantially on entry to treatment, to a level of acquisitive crime about one-eighth that reported during the last addiction period. Analysis of official records indicated that rates of acquisitive convictions were significantly lower in the in-treatment period compared to prior to entry to treatment, corroborating the changes suggested by self-report. Persisting involvement in crime in treatment was predicted by two factors: the cost of persisting use of illicit drugs, particularly cannabis, and ASPD symptom count. Treatment factors also were independently predictive of continued involvement in crime. By both self-report and official records, and adjusting for subject factors, treatment at one clinic was associated with greater involvement in crime. This clinic operated in a chaotic and poorly organized way. It is concluded that crime during methadone treatment is substantially lower than during street addiction, although the extent of reduction depends on the quality of treatment being delivered.
Adult↗
Specific identification of Mycobacterium tuberculosis with the luciferase reporter mycobacteriophage: use of p-nitro-alpha-acetylamino-beta-hydroxy propiophenone.
We have previously described a luciferase reporter mycobacteriophage (LRP) assay that can detect Mycobacterium tuberculosis and characterize mycobacterial drug susceptibility patterns within 24 to 48 h in positive cultures. One drawback of this LRP protocol is the ability of the recombinant mycobacteriophage phAE40 to infect a variety of Mycobacterium species, thus limiting its specificity for the detection of M. tuberculosis. In this study, we have (i) explored the host range of phAE40, (ii) developed a modified LRP assay that exploits the selective inhibitory effect of the compound p-nitro-alpha-acetylamino-beta-hydroxy propiophenone (NAP) against members of the M. tuberculosis complex to differentiate between the tubercle bacillus and other mycobacterial species, and (iii) tested over 300 samples, including primary clinical isolates and drug-resistant strains of M. tuberculosis, demonstrating the ability of the NAP-modified LRP assay to identify M. tuberculosis complex organisms with high degrees of sensitivity and specificity.
Bacteriological Techniques↗
Conditionally replicating luciferase reporter phages: improved sensitivity for rapid detection and assessment of drug susceptibility of Mycobacterium tuberculosis.
TM4 is a lytic mycobacteriophage which infects mycobacteria of clinical importance. A luciferase reporter phage, phAE40, has been constructed from TM4 and was previously shown to be useful for the rapid detection and drug susceptibility testing of Mycobacterium tuberculosis. However, the lytic nature of the phage results in a loss of detectable light output and limits the sensitivity of detection. We describe several strategies aimed at improving the luciferase activity generated by TM4 luciferase phages, including (i) varying the position of the luciferase gene in the phage genome, (ii) isolating host-range mutants of the phage, and (iii) introducing temperature-sensitive mutations in the phage such that it will not replicate at the infecting temperature. Several new phages generated by these methods show increased intensity of luciferase production compared to the first-generation reporter phage phAE40, and one phage, phAE88, also demonstrates an enhanced duration of luciferase activity. This has allowed the detection of as few as 120 BCG cells and the determination of drug susceptibilities of M. tuberculosis in as little as 1 day.
Bacteriological Techniques↗
Cytokine gene expression profile of circulating CD4+ T cells in active pulmonary tuberculosis.
T lymphocytes, particularly CD4+ cells, are thought to play an important role in the immune defense against Mycobacterium tuberculosis through the release of their wide array of cytokines. In vitro studies suggest that Mycobacterium-specific T-cell clones are of the TH1 subtype. Using the technique of reverse transcription-polymerase chain reaction, we have investigated the capacity for cytokine gene expression profile in ex vivo circulating CD4+ T cells from 20 patients with active pulmonary tuberculosis compared with that of 30 normal healthy tuberculin-positive volunteers. Venous blood samples were collected from the former prior to the initiation of chemotherapy. A significant increase in interleukin (IL-2) expression (p < 0.001) and a significant decrease in IL-5 expression (p < 0.0001) were observed in patients with tuberculosis but no differences were seen in the expression of IL-4 and interferon gamma between the two study groups. Our data support a TH1-like immune response in active tuberculosis.
Adolescent↗
Prevalence of sleep-disordered breathing in diastolic heart failure.
OBJECTIVE: Sleep-disordered breathing (SDB) is common in congestive heart failure. While isolated diastolic heart failure (DHF) accounts for up to a third of all cases of congestive heart failure, the prevalence of SDB in DHF is unknown. We aim to determine the prevalence and characteristics of SDB in a group of patients with symptomatic DHF. METHODS: Twenty subjects with symptomatic DHF (New York Heart Association class II or III) and isolated diastolic dysfunction on echocardiography were assessed with lung function tests, modified sleep and health questionnaire, and overnight polysomnography. Significant SDB was defined as an apnea/hypopnea index (AHI) > 10. RESULTS: Thirteen female and seven male subjects (mean age, 65+/-6.0 years; mean body mass index (BMI), 28+/-3.2) were evaluated, of whom 17 (85%) had a diagnosis of hypertension. Overall sleep quality was poor, with fragmentation and frequent arousals associated with respiratory events. Fifty-five percent of the patients had significant SDB, mainly obstructive apneas. BMI and the prevalence of hypertension were similar in patients with and without SDB. The deceleration time, an index of diastolic dysfunction, was more prolonged in the group with SDB (236+/-40 ms vs 282+/-31 ms; p<0.05). As a group, a lower minimum percentage arterial oxygen saturation during sleep, but not the AHI was associated with more severe degree of diastolic dysfunction on echocardiogram, including a lower ratio between the early peak transmittal flow velocity and the late peak atrial systolic velocity (rho=0.57; p<0.05) and a prolonged isovolumic relaxation time (rho=-0.54; p<0.05). CONCLUSIONS: SDB is common in patients with DHF. Patients with DHF and SDB may be associated with worse diastolic dysfunction than those without SDB, although a causal relationship remains to be established.
Aged↗
Recent changes in the pattern of hand injuries in Hong Kong: a regional hospital survey.
Adult inpatients with injuries to the hand admitted to the Department of Orthopaedics and Traumatology of the Prince of Wales Hospital, Hong Kong, from June 1992 to May 1993 were surveyed (n=533). The causes of injury, mechanisms involved, and the nature of injuries were recorded. The injuries were further graded according to four different scales. It was found that 65% of the injuries were sustained at work, 15% in domestic environments, 7.6% during sports or recreational activities, and 6.5% in traffic accidents. Injuries caused by heavy machinery amounted to 26.7% and the electric saw was the second most common cause of injury accounting for 9.4% of injuries. Crush injuries occurred in 37.8%. The incidence of hand injury is estimated to be 600 per 100,000 population annually. The pattern of hand injuries bears some similarities and differences to published series. A comparison with data obtained in Hong Kong in the 1970s shows that major changes have occurred. We need continual surveillance of hand injury patterns.
Journal Article↗