Use of complementary and alternative medicine in paediatric oncology patients in Singapore.
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Child↗
Biomedical subjects
C L Tan
Publications and source records attributed to C L Tan.
Paediatric extracranial germ cell tumours: a retrospective review.
INTRODUCTION: Germ cell tumours (GCTs) are rare, constituting 3% of all childhood malignancies. The aim of this study was to analyse the epidemiology and outcome of these patients. MATERIALS AND METHODS: A retrospective, cohort study was conducted on 38 paediatric patients presenting with extracranial GCTs, treated at the Singapore General Hospital, Tan Tock Seng Hospital and Kandang Kerbau Women's and Children's Hospital from 1 January 1989 to 30 June 1999. The median age at diagnosis was 1.7 years (0 to 13 years). RESULTS: There was no sex or racial preponderance. Eighteen patients (47.3%) had teratomas, 16 (42.1%) had yolk sac tumours, 1 (2.6%) had dysgerminoma and 3 (7.9%) had mixed GCTs. Thirty-four patients (89.5%) had Stage I disease, 1 (2.6%) had Stage II disease, 1 (2.6%) had Stage III disease and 2 (5.3%) had metastatic disease. Complete tumour resection was achieved in 36 of the 38 patients (95%). Cisplatin-based combination chemotherapy was given to 11 patients (28.9%). None of the patients received radiotherapy. Complications from chemotherapy included anaemia requiring packed red cell transfusion (n = 3), Port-a-cath sepsis requiring removal (n = 1), febrile neutropenia (n = 1) and nephropathy (n = 1). CONCLUSION: Using the Kaplan-Meier life tables, the overall and event-free survivals at 10 years for the patients with malignant GCTs were 96% and 88%, respectively, with a mean follow-up period of 5.1 years (0.7 to 10 years). The majority of the patients presented with early Stage I disease and this contributed to our high survival rate.
Adolescent↗
Electronic detection of single-base mismatches in DNA with ferrocene-modified probes.
Genotyping and gene-expression monitoring is critical to the study of the association between genetics and drug response (pharmacogenomics) and the association of sequence variation with heritable phenotypes. Recently, we developed an entirely electronic method for the detection of DNA hybridization events by the site-specific incorporation of ferrocenyl derivatives into DNA oligonucleotides. To perform rapid and accurate point mutation detection employing this methodology, two types of metal-containing signaling probes with varying redox potentials are required. In this report we describe a new ferrocene-containing phosphoramidite 9 that provides a range of detectable redox potentials. Using automated DNA/RNA synthesis techniques the two ferrocenyl complexes were inserted at various positions along oligonucleotide probes. Thermal stability analysis of these metal-containing DNA oligonucleotides indicates that incorporation of 9 resulted in no destabilization of the duplex. A mixture of oligonucleotides containing compounds 9 and I was analyzed by alternating current voltammetry (ACV) monitored at the 1st harmonic. The data demonstrate that the two ferrocenyl oligonucleotide derivatives can be distinguished electrochemically. A CMS-DNA array was prepared on an array of gold electrodes on a printed circuit board substrate with a self-assembled mixed monolayer, coupled to an electronic detection system. Experiments for the detection of a single-base match utilizing two signaling probes were carried out. The results demonstrate that rapid and accurate detection of a single-base mismatch can be achieved by using these dual-signaling probes on CMS-DNA chips.
Base Pair Mismatch↗
[Detection of brain vascular diseases with CT angiography].
OBJECTIVE: To identify the diagnostic effect of spiral CT in brain vascular diseases. METHODS: Sixty four patients underwent CT angiography, including 22 patients with subarachnoid hemorrhage (SAH), 6 patients with oculomotor nerve paralysis, 5 patients with brain substance hemorrhage, 6 patients with arteriovenous malformation (AVM), 4 patients with mass or aneurysm, 5 patients with brain infarction, 16 patients with epilepsy or headache and dizzy. 8 cases also underwent digital subtraction angiography (DSA), 4 cases were performed operation in 64 cases. RESULTS: Spiral computed tomography angiography (SCTA) was all succeeded in 64 cases. 26 aneurysms and 8 AVMs were found by SCTA; in 6 of 8 cases of AVMs, their supply arteries and drainage veins were clearly displayed; SCTAs of 5 cases with substance hemorrhage were normal; in 1 of 5 cases with cerebral hemisphere infarction, its internal carotid obstruction was demonstrated by SCTA; the results of 12 SCTAs were identical with the results of their DSA or operation. CONCLUSION: SCTA is a useful non-invasive inspection method for detecting brain vascular diseases such as aneurysms and AVMs.
Adolescent↗
2nd Chapter of Paediatricians Lecture: the future of paediatrics in Singapore.
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Education, Medical, Graduate↗
Transcription of the interferon gamma (IFN-gamma )-inducible chemokine Mig in IFN-gamma-deficient mice.
MuMig or Mig (murine monokine induced by interferon gamma) is a CXC chemokine whose induction is thought to be strictly dependent on interferon gamma (IFN-gamma). Here we have studied the expression of this chemokine gene in various organs of mice infected with vaccinia virus. We have employed animals deficient in either IFN-gamma (IFN-gamma(-/-)), or receptors for IFN-alpha/beta, IFN-gamma, or both IFN-alpha/beta and IFN-gamma (DR(-/-)) to dissect out the role of interferons in the induction of Mig during the host response to virus infection. Our data show that Mig mRNA and protein are expressed in organs of vaccinia virus-infected IFN-gamma(-/-) mice, albeit at lower levels compared with infected, wild-type animals. In the DR(-/-) mice and in IFN-gamma(-/-) mice treated with a neutralizing antibody to IFN-alpha/beta, Mig mRNA transcripts were completely absent. Our data indicate that, in vaccinia virus-infected IFN-gamma(-/-) mice, Mig mRNA expression is mediated through the interaction between IFN-gamma responsive element 1 (gammaRE-1) and IFN-alpha/beta-induced STAT-1 complex referred to as IFN-gamma response factor 2 (gammaRF-2). Further, our findings support the view that gammaRF-2 is the IFN-alpha/beta induced STAT-1 complex, IFN-alpha-activated factor. We have found that, in the absence of IFN-gamma, IFN-alpha/beta are able to induce Mig in response to a viral infection in vivo.
Animals↗
Squalamine analogues as potential anti-trypanosomal and anti-leishmanial compounds.
This paper concerns the synthesis of various simplified analogues of the novel anti-microbial agent, squalamine. The compounds were then investigated for activity against Trypanosoma brucei, the causative agent of African trypanosomiasis, Trypanosoma cruzi, the causative agent of Chagas disease and Leishmania donovani, the causative agent of visceral leishmaniasis. Several compounds showed in vitro activity, especially against T. brucei and L. donovani. However, one compound showed poor in vivo activity.
Animals↗
Ecthyma gangrenosum in a patient with hypogammaglobulinemia.
Ecthyma gangrenosum is a characteristic skin lesion that is caused by Pseudomonas aeruginosa (P. aeruginosa) in the majority of cases. Systemic P. aeruginosa usually complicates debilitating conditions like leukaemia, burns and cystic fibrosis. We report a patient with underlying hypogammaglobulinemia who developed ecthyma gangrenosum secondary to P. aeruginosa septicaemia, which was potentially life-threatening. Recognition of the characteristic skin lesions with prompt initiation of appropriate antibiotics and intravenous immunoglobulins were life-saving. A review of the English literature reports three other cases of ecthyma gangrenosum in patients with underlying hypogammaglobulinemia.
Agammaglobulinemia↗
The incidence of IDDM in Singapore children.
OBJECTIVE: To determine the incidence of insulin dependent diabetes mellitus (IDDM) in children 0-12 years of age in Singapore, which has a population of 2.9 million. METHODS: The primary source was a 2-year phone and mail survey of doctors in the government and government restructured hospitals and the private sector. The secondary source was the membership records of the Diabetes Society of Singapore. RESULTS: Using the capture-recapture method, ascertainment was assessed to be 92.2% complete. The age standardised incidence rate was 2.46 per 100,000 children 0-12 years old, for the period 1992-1994 (95% confidence interval: 2.16-2.75). The data seemed to indicate a rising incidence of IDDM in this population, being 1.4/100,000 in 1992, 2.4/100,000 in 1993 and 3.8/100,000 in 1994. The male: female ratio is 1:1.85. There was seasonal variation with fewer cases from July to October and more from November to May. Five percent of patients had a first degree relative with IDDM. Malays appeared to have a lower incidence (1.23/100,000) compared to the Chinese (2.25/100,000) and the Indians (5.78/100,000). CONCLUSIONS: The incidence of IDDM in Singapore children is similar to that reported for Hong Kong and Japan, but higher than that for Shanghai. The female preponderance is similar to that seen in other Asian population. The data suggests a rising incidence of IDDM in Singapore and differences in incidence between the Malays, Chinese and Indians, but further observations are needed.
Child↗
Phaeochromocytoma--a rare cause of hypertension in an 11-year-old girl.
Severe sustained hypertension occurs in only 0.1% of the paediatric population and only about 2% of these patients will have an underlying endocrine cause. Phaeochromocytoma as a catecholamine-secreting tumour causing severe hypertension is exceedingly rare in children. A high index of suspicion and an awareness of the clinical spectrum are therefore necessary to make the diagnosis. Phaeochromocytomas can have protean manifestations which may be mistaken for a variety of clinical conditions. We highlight the problems encountered in making the diagnosis in an 11-year-old Chinese girl who presented with sustained hypertension, heart failure and transient renal impairment with two normal 24-hour urinary vanillyl mandelic acid (VMA) results before a third produced the diagnosis. We emphasize that total reliance on a single biochemical urinary screening is not acceptable. The measurement of urinary catecholamines or their metabolites increases the sensitivity of diagnosis. We recommend that in situations where biochemical screening is doubtful, appropriate imaging should be undertaken to exclude the diagnosis.
Adrenal Gland Neoplasms↗
A recent case of congenital malaria in Singapore.
We report a case of congenital malaria in a 2-month-old baby girl, born in Singapore of a Singaporean mother, who presented with fever for one week, gross hepatosplenomegaly and anaemia (haemoglobin 5.6 g/dL) and thrombocytopenia. Peripheral blood films showed Plasmodium vivax. There was no local transmission at that time, but the mother had spent the first 6 months of her pregnancy in Pakistan, where she had been treated for prolonged fever at 4 months amenorrhoea with ibuprofen alone. The mother and 2 siblings were asymptomatic and repeatedly tested negative on blood films for malaria parasites, but the mother tested positive for antibodies to Plasmodium on the Fluorescent Antibody Test. The child was treated with oral chloroquine and made an uneventful recovery. We postulate that this is believed to be the first recent case of congenital malaria in Singapore since it was declared malaria free in 1982. The diagnosis should be considered in babies of mothers who have travelled to places where malaria is endemic, as maternal infection may be unrecognised, and the child may be asymptomatic at birth.
Antimalarials↗
Early prenatal diagnosis of beta-thalassaemia in Singapore.
beta-thalassaemia is one of the commonest autosomal recessive genetic diseases in the Singapore population. In the homozygous form, it results in a severe anaemia, requiring monthly transfusion for survival. Because of the less than satisfactory treatment available for the condition, prenatal diagnosis has always been an option for couples at-risk. The available method was globin chain analysis of foetal blood, obtained at 18 to 20 weeks of gestation. Affected pregnancies would then be diagnosed and require termination in the mid to late trimester. A relatively newer technique, chorionic villus sampling (CVS), allows foetal material to be obtained in the first trimester. However, analysis of the foetal tissue requires direct gene studies to be performed. The aim of this study was to evaluate the feasibility of this analysis in couples at-risk for beta-thalassaemia in Singapore. Sixteen couples who were at-risk for a child with beta-thalassaemia major were offered prenatal diagnosis. All of them opted for CVS as compared to foetal blood sampling. The mutations in the beta-globin gene in these couples at-risk were identified. Direct gene analysis was then performed on the foetal sample, using a variety of molecular techniques. These included reverse dot-blot hybridisation, allele-specific oligonucleotide hybridisation, restriction enzyme digests and direct analysis of amplified products. DNA profiling was done for each case to exclude definitively the possibility of maternal tissue contaminating the foetal sample. The results in all these cases were unequivocal. The procedure of CVS itself was uneventful in these 16 couples. Procedural-associated foetal loss was nil. Prenatal diagnosis in the first trimester allows early termination of an affected pregnancy with significantly less maternal morbidity and prenatal anxiety. It also results in greater patient acceptability of the procedure and plays a key role in the prevention of this devastating genetic disease.
Chorionic Villi Sampling↗
Rapid antenatal diagnosis of beta-thalassemia in Chinese caused by the common 4-bp deletion in codons 41/42 using high-resolution agarose gel electrophoresis and heteroduplex detection.
The 4-bp deletion in codons 41/42 (-TTCT) in the beta-globin gene is a common mutation that causes beta-thalassemia in Chinese. A simple method, which involved PCR amplification of the relevant region, was used for the antenatal diagnosis of a fetus at risk for this mutation. The fetal PCR product showed a single fragment of normal size on MetaPhor gel. The homozygous normal status was further confirmed by the generation of heteroduplexes only after addition of homozygous mutant DNA.
Base Sequence↗
Beta-thalassemia mutations in Singapore--a strategy for prenatal diagnosis.
The strategy for early prenatal diagnosis of beta-thalassemia in Singapore by direct detection of the mutant beta-globin gene requires the spectrum of mutations producing the disorder in this population to be characterized. We analyzed 134 beta-thalassemia alleles from Singapore by specific oligonucleotide hybridization after DNA amplification, using a nonradioactive enhanced chemiluminescence detection system. The mutations were identified in 90% of the alleles using five oligonucleotide probes for the following mutations: codons 41/42 (deletion-TCTT), IVS II nt 654 (C-->T), codon 17 (A-->T), IVS I nt 5 (G-->C), and -28 TATA box (A-->G). Together with the strategy of direct sequencing, a total of 97% of the mutations were identified. In the Chinese subpopulation, 97% of the mutations were detected by the oligonucleotide probes. Using just four oligonucleotide probes would identify 96% of the mutations, and 76% of the mutations were accounted for by codon 41/42 (-TCTT) and IVS II nt 654 (C-->T) mutations. Thus in this subpopulation early prenatal diagnosis would be possible in virtually all the affected families.
Alleles↗
Cytogenetic abnormalities in childhood acute lymphoblastic leukaemia.
A retrospective study of 50 children newly diagnosed with acute lymphoblastic leukaemia (ALL) from December 1988 to November 1993 was carried out, examining the disease conditions and cytogenetic abnormalities. Of the 50 children, 8 had no cytogenetic examination of the marrow at the time of diagnosis and 7 had a poor yield from the marrow. Fifty percent of the remaining children had a normal karyotype. The rest of the children had hyperdiploidy and structural chromosomal abnormalities (mainly translocation and deletions) in equal proportions. Overall mortality of the whole group was about 26% with 2 lost to follow-up. There were 2 patients who relapsed while on treatment of whom 1 died. Cytogenetic abnormalities were correlated with clinical variables known to have prognostic significance. The group with hyperdiploidy had a significantly lower mean total white count at presentation and none of them died. The group with translocation abnormalities had a lower mean platelet count at presentation. Almost all in the group with hyperdiploidy and a great majority of the other 2 groups with normal or structural cytogenetic abnormalities were of B cell lineage. The median survival times for the hyperdiploid, normal karyotype and translocation patients were 1800 days, 1450 days and 700 days respectively.
Burkitt Lymphoma↗
Use of intravenous midazolam for sedation in children undergoing ward procedures.
Midazolam is a water-soluble benzodiazepine with low toxicity. It has anxiolytic and sedative effects. This study assessed the efficacy and tolerance of this drug for sedation in various ward procedures. Pethidine was added to bone marrow aspirations for analgesia. 57 children with the mean age of 48 months and mean weight of 15.7 kilograms were studied. The dose of midazolam used to sedate adequately 86% of the children was 0.73mg/kg, the average onset of sedation was 4.3 minutes and mean duration was about 88 minutes. 47.5% were completely sedated, whereas 38.5% were only partially sedated. In 14%, sedation was not achieved at all. There was a statistically significant drop in blood pressure after sedation but this was not associated with any clinical effects. Hypoventilation was not detected in this study.
Child↗
Vesicoureteric reflux and renal scarring in children--a local perspective.
This study was undertaken to determine the extent of primary vesicoureteric reflux and renal scarring in patients investigated for urinary tract infection in the Singapore General Hospital between 1983 and 1988. The clinical profile of patients and possible clinical features associated with renal scarring were analysed. These findings serve as a useful guide in the investigation and management of VUR in our population. The incidence of vesicoureteric reflux among patients investigated for documented urinary tract infection was high at 32.9%. The mean age at presentation was 15.2 months. Almost all patients were less than five years-old. A male predominance was noted in affected infants. High grade refluxes of Grade IV or more (International Reflux Study Classification) were found in 45.7/patients and were associated with a higher incidence of recurrent urinary tract infection (p less than 0.05). Thirty-four 99mTc-dimercaptosuccinic acid scans were done and 46.4% of refluxing kidneys showed renal scars. The incidence of renal scarring was significantly higher in patients presenting at an early age (less than 2 years), in high grade reflux and in recurrent urinary tract infection (p less than 0.05; p less than 0.01 and p less than 0.001 respectively). Therefore all children with documented urinary tract infection who are less than five years old and especially male infants should be fully investigated for early detection and treatment of vesicoureteric reflux and renal scars. Kidneys with vesicoureteric reflux at risk of scarring appeared to be those with early presentation, high grade reflux and recurrent urinary tract infection whose management should therefore be vigorous.
Child, Preschool↗
Acute glomerulonephritis--changing patterns in Singapore children.
This study compared the pattern of acute glomerulonephritis (AGN), a disease known to be influenced by socioeconomic and environmental factors, in children 12 years and under, for the years 1971 and 1985. All children admitted to the four major paediatric departments with haematuria and at least two of the following (oedema, hypertension or oliguria) had an initial diagnosis of AGN. A sample population from one unit from 1980 to 1984 showed that over 70% of these children had evidence of a post-streptococcal aetiology. In 1971, 411 children were admitted with AGN, as compared with only 58 in 1985. The age-sex-race standardized rates for 1971 and 1985 were 0.632 and 0.023/1,000 children 12 years and under, respectively (P less than 0.001). The mean age of presentation was lower in 1971. Over this period, Singapore saw a threefold rise in the gross national product, accompanied by rapid urbanization. On analysis of the housing pattern, only 31% of the children lived in high-rise apartments in 1971, in contrast with 86% in 1985 (P less than 0.001). The majority of non-apartment dwellers had homes in rural districts. From an epidemiological perspective, factors which could have led to the highly significant decline in prevalence of AGN in Singapore children included improvement in the socioeconomic status and health care system, and urbanization of the country.
Acute Disease↗