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Biomedical subjects

G C Chan

Publications and source records attributed to G C Chan.

At least 55 records · Page 3Linked to original sources
PubMed1998

End tidal carbon monoxide concentration in childhood haemolytic disorders.

OBJECTIVES: Endogenous carbon monoxide (CO) is produced mainly by heme catabolism. As CO is excreted solely by the lung, a simple technique for measuring the end tidal carbon monoxide (ETCO) level was assessed as a method for screening for haemolytic disease in children. METHODS: Two end expiratory breath samples were collected from normal children and from children with haemolytic disease using a one way valve connector between a mouth piece and an anaesthetic bag. The samples were analysed by gas chromatography for CO and carbon for dioxide (CO2). The CO2 value was used to normalise the CO value to an alveolar concentration. Carboxyhaemoglobin (HbCO) also was measured in the patient group for correlation analysis with ETCO. RESULTS: A total of 21 children with beta thalassaemia major, 15 children with other haemolytic diseases (hereditary spherocytosis n=8, haemoglobin H disease n=3 and thalassaemia intermedia n=4) and 23 normal children were studied. The mean ETCO concentrations in the three groups were 3.21 p.p.m., 7.41 p.p.m. and 0.69 p.p.m., respectively, which were significantly different from each other (P<0.0001). There was a significant correlation between ETCO and HbCO in the patient groups (r=0.85; P<0.0001). CONCLUSIONS: The end expiratory breath collection device is a simple and feasible sample collection method. The results confirm that ETCO can be used clinically to distinguish children with a variety of haemolytic disorders from normal subjects.

Adolescent↗
PubMed1997

Clinical presentation, hematologic features and treatment outcome of childhood acute lymphoblastic leukemia: a review of 73 cases in Hong Kong.

Seventy-three consecutive cases of childhood acute lymphoblastic leukemia (ALL) diagnosed and managed in Queen Mary Hospital over a 10-year period from 1985 to 1994 were retrospectively analysed for their presenting features and treatment outcome. The 48 boys and 25 girls ranged in age from 0.4 to 14.2 years (median: 4.3 years). Bone and joint pain was a relatively common presenting feature besides fever, hepatosplenomegaly and lymphadenopathy. Immunophenotyping of blast cells showed: 51 B-cell precursor ALL, one B-ALL, 10 T-ALL and three myeloid-antigen positive ALL. Eight cases were unclassified since immunophenotyping had not been performed. Out of the 73 patients, treatment outcome was analysed in 20 cases treated with UKALL-VIII regimen and 28 cases treated with either the UKALL-XI regimen or the Hong Kong Children Cancer Study Group (HKCCSG) protocol which was modelled upon UKALL-XI. Although complete remission rates were similar between the two groups, patients treated with the former regimen that was less intensified suffered more relapses than the latter (56 per cent versus 21 per cent, P = 0.04). There were, however, no significant differences both in event-free survival (38.2 +/- 11.2 per cent versus 71.3 +/- 9.3 per cent, P = 0.12) and overall survival (70.0 +/- 10.2 per cent versus 79.6 +/- 8.3 per cent, P = 0.41) between the two groups at 3 years by long-rank test. With the use of risk-directed therapy and improved supportive care, two-thirds of our patients are able to enjoy long-term event-free survival.

Adolescent↗
PubMed1997

Infection complicating percutaneous liver biopsy in liver transplant recipients.

There is controversy about the frequency of and risk factors for infectious complications of percutaneous liver biopsy in liver transplant recipients. The aim of this study was to identify the incidence and nature of complications associated with liver biopsy after orthotopic liver transplantation (OLT), with particular emphasis on infection. The medical records of all patients undergoing OLT between January 1990 and August 1994 were reviewed retrospectively to identify complications requiring hospitalization within one week of percutaneous liver biopsy. The nature and severity of complications were recorded and possible risk factors for infectious complications were examined. One hundred ninety-eight patients underwent 1,136 percutaneous liver biopsies. There were eleven complications (0.96%), including as follows: 7 infections, 3 bleeding episodes, and 1 vasovagal reaction. Infections after percutaneous liver biopsy included fever and bacteremia (n = 6), and fever without bacteremia (n = 1). All infections developed only in patients with underlying biliary tract abnormalities; the frequency of infection was higher (9.8%) in patients with choledochojejunostomy when compared with those with choledochocholedochostomy (1.4%). Bacteremia was more likely caused by skin flora in patients with choledochocholedochostomy (CDC) and by enteric bacteria in patients with choledochojejunostomy (CDJ). All infections were treated successfully with parenteral antibiotics. We conclude that biliary tract abnormalities are the primary risk factors for infection after percutaneous liver biopsy, although the risk is higher in patients with CDJ than with CDC. These data support the use of antibiotic prophylaxis before percutaneous liver biopsy in OLT recipients with biliary tract abnormalities.

Anastomosis, Roux-en-Y↗
PubMed1997

Cytogenetic abnormalities in pediatric myelodysplastic syndrome: a report of three cases.

Three consecutive cases of pediatric myelodysplastic syndrome (MDS) diagnosed over a three-year period in Queen Mary Hospital, Hong Kong, were described. Depending on the classification system used, they comprised two cases of chronic myelomonocytic leukemia (CMMoL) of which one can be reclassified as juvenile chronic myeloid leukemia (JCML) and one cases of refractory anemia with excess of blasts (RAEB) or an alternative diagnosis of atypical CML. Cytogenetic abnormalities were detected in all of them on examination of bone marrow cells. Of the two CMMoL, one had monosomy 21, whereas the other had hypodiploidy. The patient with RAEB had a complex karyotype of 46,X,del(X)(q24),t(1;7) (p22;q32),add(15)(q26)(8). The balanced translocation (1;7) seen in this patient was exceedingly rare and, to the best of our knowledge, was reported only twice in the literature. The karyotypic abnormalities that we saw in our patients were not well recognized in pediatric MDS. This report emphasizes the importance of cytogenetic study in children suspected of suffering from MDS, which remains a rare disorder of childhood, and a need to rationalize current classification schemes.

Child↗
PubMed1997

Myelodysplastic syndrome in children: differentiation from acute myeloid leukemia with a low blast count.

To evaluate diagnostic criteria, disease characteristics, and the clinical course of pediatric myelodysplastic syndrome (MDS), we reviewed 327 consecutive cases diagnosed with de novo acute myeloid leukemia (AML) or MDS at St Jude Children's Research Hospital between February 1980 and January 1993. Among 49 cases with <30% marrow blasts (consistent with FAB criteria and common diagnostic practice for MDS), eight had karyotypes associated with de novo AML (four with t(8;21)(q22;q22) and one each with inv(16)(p13q22), t(11;17)(q23;q21), t(9;11)(p22;q13), and i(1)(ql0)). We termed these cases AML with a low blast count (AML-LBC) and compared their clinical and morphologic features with those of the remaining 41 cases. AML-LBC cases had little or no hematopoietic dysplasia. MDS cases consisted of refractory anemia (RA, n=6), RA with ring sideroblasts (n=2), RA with excess blasts (RAEB, n=4), RAEB in transformation (n=14), and chronic myelomonocytic leukemia (n=15). Most had moderate/severe or multilineage hematopoietic dysplasia, with significantly higher dysplasia scores than AML-LBC cases (P=0.007). Only 30% of patients with MDS achieved complete remission (CR) after two cycles of AML-directed therapy, compared with 88% of patients with AML-LBC (P=0.0001); MDS patients tended to experience prolonged severe cytopenias with chemotherapy. The 4-year survival for MDS patients was 23% +/- 7% (s.e.), vs 50% +/- 18% (s.e.) for AML-LBC (P=0.048). AML-LBC patients frequently had chloromas; none were seen in MDS patients. We conclude that the 30% blast threshold is ineffective for separation of AML and MDS in pediatric patients, and that genetic data should be included in this decision process. AML-LBC, defined by <30% blasts in bone marrow and cyto- (or molecular) genetic abnormalities associated with de novo AML, and characterized by absent or mild marrow dysplasia, is biologically and clinically distinct from MDS and should be treated as de novo AML. Outcome in pediatric MDS remains poor, and new treatment strategies are needed for these patients.

Acute Disease↗
PubMed1997

The ageing worker.

In Singapore, the age for retirement has increased from 55 years to 60 years, and will eventually reach 67 years. At the same time, the proportion of workers aged above 45 years will continue to increase. The World Health Organisation has reported that in 1980, 32% of the working population were older than 45 years of age in countries of the Organisation for Economic Co-operation and Development (OECD). This proportion is expected to rise to 35.5% in the year 2000 and 41.3% in the year 2055. What are the implications of the emergence of an ageing workforce? This population represents a special group of individuals in the workforce that have special health, occupational and environmental needs. On the one hand, they have the problem of a reduction in physical work capacity, decreased adaptability, and a generally lower health status. On the other, ageing workers are more experienced and have greater expertise. They are also usually more motivated and may generally have a more positive attitude when compared with younger workers. Society, as well as health care professionals, needs to respond to this issue of an ageing workforce. The response should be three pronged. Firstly, prevention of the premature decline of physical capacities and adaptability of the worker could be addressed by health promotion and continuing job training. Secondly, some measures for adjusting work demands in accordance with functional capacities of the individual are needed. Thirdly, employers and fellow workers should be educated on the strengths of the ageing worker, and the capacity of such workers to continue contributing because of their experience, motivation and skills. If implemented, these measures would ensure a path towards productive ageing. The end results would be that ageing workers would have their functional capacity maintained, the concept of "age-adjusted workload" would be a reality, and ageing workers would not be discriminated against, but instead have their contributions to society maximised.

Aged↗
PubMed1996

Differential regulation of type I and type VIII Ca2+-stimulated adenylyl cyclases by Gi-coupled receptors in vivo.

Coupling of intracellular Ca2+ to cAMP increases may be important for some forms of synaptic plasticity. The type I adenylyl cyclase (I-AC) is a neural-specific, Ca2+-stimulated enzyme that couples intracellular Ca2+ to cAMP increases. Since optimal cAMP levels may be crucial for some types of synaptic plasticity, mechanisms for inhibition of Ca2+-stimulated adenylyl cyclases may also be important for neuroplasticity. Here we report that Ca2+ stimulation of I-AC is inhibited by activation of Gi-coupled somatostatin and dopamine D2L receptors. This inhibition is due primarily to Gialpha and not betagamma subunits since coexpression of betagamma-binding proteins with I-AC did not affect somatostatin inhibition. However, betagamma released from Gs did inhibit I-AC, indicating that the enzyme can be inhibited by betagamma in vivo. Interestingly, type VIII adenylyl cyclase (VIII-AC), another Ca2+-stimulated adenylyl cyclase, was not inhibited by Gi-coupled receptors. These data indicate that I-AC and VIII-AC are differentially regulated by Gi-coupled receptors and provide distinct mechanisms for interactions between the Ca2+ and cAMP signal transduction systems. We propose that I-AC may be particularly important for synaptic plasticity that depends upon rapid and transient cAMP increases, whereas VIII-AC may contribute to transcriptional-dependent synaptic plasticity that is dependent upon prolonged, Ca2+-stimulated cAMP increases.

Adenylate Cyclase Toxin↗
PubMed1996

Malignant peripheral neuroectodermal tumor in an infant with neurofibromatosis type 1.

A case of multifocal malignant peripheral neuroectodermal tumor (PNET) arising from a plexiform neurofibroma in a 4-month-old Chinese boy with neurofibromatosis type 1 (NF-1) is described. Cytogenetic culture demonstrated hypotriploid karyotype with an abnormal clone characterized by 59-60, XY, +2, +3, +6, +8, +8, +12, +i(13)(q10), +der(14)t(1;14)(q21;q32), +16, +19, +20, +mar[cp3] with no apparent abnormality of chromosome 17. The child was treated with combination chemotherapy comprising ifosphamide, vincristine and doxorubicin. Despite initial partial response the child finally died of tumor progression and pulmonary metastases 8 months after diagnosis. We believe this is the first reported case of PNET in a child with NF-1 and may support an association between these two disorders of neural crest origin.

Fatal Outcome↗
PubMed1995

Paradoxical response of a pineal immature teratoma to combination chemotherapy.

A case of primary intracranial germ cell tumour is reported in a 5-year-old Chinese boy who presented with symptoms and signs of increased intracranial pressure. Computed tomography (CT) scan of the brain revealed a multicystic tumour over the pineal region. Stereotactic biopsy yielded enteric epithelium and isolated cells with hyperchromatic nuclei and high nuclear-to-cytoplasmic ratio, suggesting the diagnosis of an immature teratoma. Grossly elevated serum and cerebrospinal fluid (CSF) levels of alpha-fetoprotein and mildly elevated levels of beta human chorionic gonadotrophin suggested the simultaneous presence of embryonal tissues. Combination chemotherapy with cisplatin, etoposide, and bleomycin resulted in a gradual but complete normalisation of the serum and CSF tumour markers. Paradoxically, the patient's consciousness deteriorated and repeat CT scan after 3 months of treatment showed that the tumour was actually increasing in size. Complete surgical removal was attempted and histologic sections of the specimen revealed only mature teratomatous tissues. The child is now well and remains disease-free with minimal left hemiparesis 12 months after completion of treatment. This case illustrates the importance of combined neoadjuvant chemotherapy and surgery in the management of intracranial non-germinomatous germ cell tumour harbouring both germ cell and teratomatous components, while monitoring of both biochemical and radiological parameters are necessary in assessing the clinical behaviour of mixed germ cell tumours.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis.

The t(12;21)(p13;q22) is identified by routine cytogenetics in less than 0.05% of pediatric acute lymphoblastic leukemia (ALL) patients. This translocation encodes a TEL/AML-1 chimeric product comprising the helix-loop-helix domain of TEL, a member of the ETS-like family of transcription factors, fused to AML-1, the DNA-binding subunit of the AML-1/CBF beta transcription factor complex. Both TEL and AML-1 are involved in several myeloid leukemia-associated translocations with AML-1/CBF beta being altered in 20-30% of de novo acute myeloid leukemia (AML) cases. We now demonstrate that a TEL/AML1 chimeric transcript encoded by a cryptic t(12;21) is observed in 22% of pediatric ALL, making it the most common genetic lesion in these patients. Moreover, TEL/AML1 expression defined a distinct subgroup of patients characterized by an age between 1 and 10 years, B lineage immunophenotype, non-hyperdiploid DNA content and an excellent prognosis. These data demonstrate that molecular diagnostic approaches are invaluable in identifying clinically distinct subgroups, and that the AML1/CBF beta transcription complex is the most frequent target of chromosomal rearrangements in human leukemia.

Base Sequence↗
PubMed1993

Disseminated mediastinal carcinoma with chromosomal translocation (15;19). A distinctive clinicopathologic syndrome.

BACKGROUND: A case of disseminated mediastinal carcinoma probably of thymic origin is reported in a 5-year-old boy with an anterior mediastinal mass associated with superior vena cava obstruction, tracheal deviation, right malignant pleural effusion, and evidence of bone metastasis. The diagnosis was based on findings of radiologic localization, light and electron microscopic study, and immunohistochemistry. The patient received combination chemotherapy but died of progressive disease. METHODS: Cytogenic study on the pleural fluid was attempted, and a literature search for similar chromosomal aberration was performed. RESULTS: Cytogenetic study of tumor cells from the pleural fluid revealed a clonal chromosomal abnormality of t(15;19)(q12;p13.1). Two patients with similar disease were reported in the English literature; their clinical courses, immunohistochemical findings, and t(15;19) were almost identical to those of the patient reported in this study. CONCLUSION: The authors suggest that this translocation may be specific to thymic carcinoma and may indicate a particularly aggressive form of the disease. Carcinomas are rare in children, so the chromosomal translocation may serve as a helpful marker for the diagnosis.

Adult↗
PubMed1991

Delayed secondary glucocorticoid response elements. Unusual nucleotide motifs specify glucocorticoid receptor binding to transcribed regions of alpha 2u-globulin DNA.

Glucocorticoids stimulate the transcription of rat alpha 2u-globulin (RUG) genes. Because this induction occurs after a time lag of several hours and is blocked by inhibitors of protein synthesis, it exemplifies a delayed secondary response to steroid hormones. In this report, we show that a region of RUG-transcribed DNA (approximately +1800 to +2174) contains multiple footprint sites for glucocorticoid receptor that are, apparently, organized into at least three independent binding clusters. The DNA sequences bound by the receptor and the location of binding sites were determined. A family of sequences related to half-sites of the consensus primary glucocorticoid response element (GRE) is discernible at each cluster of sites. Compared to the consensus GRE, which contains two pseudo-palindromic hexanucleotides arranged in a tail-to-tail fashion and separated by three bases, the arrangements of hexanucleotides within this segment of RUG DNA are unusual and heterogeneous. Methylation interference of a binding cluster containing three receptor footprints demonstrates that certain guanines of the GRE-like hexanucleotides are essential for efficient receptor binding. A synthetic 29-base pair (bp) RUG element, containing one receptor footprint from this cluster, selectively binds the receptor. Within this 29-bp element, six nucleotides separate two directly repeated copies of GRE-like hexanucleotides. RUG DNA fragments containing all or part of the three binding clusters, including the 29-bp element, confer a delayed secondary hormone responsiveness upon a linked heterologous promoter and reporter gene in stably transfected cell lines. We speculate that the unusual DNA sequence motifs of the receptor-binding sites are crucial for the generation of certain delayed secondary responses.

Alpha-Globulins↗
PubMed1990

Purified glucocorticoid receptors bind selectively in vitro to a cloned DNA fragment that mediates a delayed secondary response to glucocorticoids in vivo.

We have identified and characterized a 206-base-pair region downstream from rat alpha 2u-globulin promoter that specifically mediates a delayed secondary response to glucocorticoids. Unlike positive primary glucocorticoid response elements (GREs), this regulatory element, termed delayed sGRE, dictates an inductive process preceded by a time lag of several hours and blocked by the protein synthesis inhibitor cycloheximide. Reminiscent of GREs and negative GREs (nGREs), a delayed sGRE confers hormonal regulation upon a linked heterologous promoter from a downstream position with respect to transcription start site and, remarkably, also interacts selectively with purified glucocorticoid receptor. These results imply that receptor binding to a delayed sGRE in vivo may mediate certain secondary responses to glucocorticoid hormones.

Alpha-Globulins↗
PubMed1988

Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial.

To assess the efficacy and safety of Adriamycin (Adria Laboratories, Columbus, OH) in inoperable hepatocellular carcinoma (HCC), 60 patients were randomized to receive Adriamycin 60 to 75 mg/m2 at 3-week intervals and 46 patients to receive no antitumor therapy. The median survival rate of the Adriamycin group was 10.6 weeks; that of the group receiving no antitumor therapy was 7.5 weeks (P = 0.036). Adriamycin induced tumor regression of 25% to 50% in 5% of patients and of over 50% in only 3.3% of patients. It caused fatal complications (septicemia and cardiotoxicity) in 25% of patients. The severity of neutropenia leading to septicemia for a particular dose was unpredictable. Four of eight patients who developed cardiotoxicity received less than 500 mg/m2 of Adriamycin. We conclude that Adriamycin is not an ideal drug for the treatment of inoperable HCC.

Adult↗
PubMed1986

Factors associated with cannabis nonuse and cessation of use: between and within survey replications of findings.

Multivariate analyses (Multiple Classification Analyses) of data obtained from repeated surveys (1981 and 1983) of students (grades 7-13) supported the separate consideration of three aspects of cannabis use and nonuse: not trying cannabis; trying and quitting cannabis use; and trying and continuing cannabis use. Marked consistency was found in results obtained from between and within-survey replications. Many variables which exhibited bivariate relationships with cannabis use were not significant when considered multivariately. Few variables were related to both trying vs. continuing cannabis use. Variables which were expected to be related to cannabis use failed to show a significant relationship, most notably those measuring perceived threat of legal consequences, problems at home, problems outside the home, and threats to health. Methodological and substantive, especially educational/prevention, implications are highlighted.

Adolescent↗