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Biomedical subjects

G C Chan

Publications and source records attributed to G C Chan.

At least 19 recordsLinked to original sources

Carotid intima-media thickness is increased and related to arterial stiffening in patients with beta-thalassaemia major.

An increased iron store has been linked to the risk of atherosclerosis. The carotid intima-media thickness (IMT), stiffness index, Young's elastic modulus (YEM), and augmentation index were determined in 20 patients with beta-thalassaemia major. Compared with controls, patients had greater IMT (P < 0.001), YEM (P = 0.005), and stiffness (P = 0.009) and augmentation (P = 0.03) indices. The odds ratio for increased IMT in patients was 39. Carotid IMT correlated with YEM (P = 0.036), stiffness index (P = 0.036) and augmentation index (P = 0.006). Multivariate analysis identified patient status (P < 0.001) as the only significant determinant of IMT. These findings suggest the possibility of premature atherosclerosis in beta-thalassaemia major patients.

Adult↗

Parental knowledge, attitudes and antibiotic use for acute upper respiratory tract infection in children attending a primary healthcare clinic in Malaysia.

INTRODUCTION: A study was carried out in a primary healthcare clinic in the Hulu Langat district of Malaysia to assess the parental knowledge, attitudes and antibiotic use for common childhood acute upper respiratory tract infection (URTI). METHODS: A cross-sectional study involving 421 parents, who were surveyed by using an interviewer-administered questionnaire, from April to June 2001. RESULTS: Approximately 59 percent of parents from this study believed that weather was the main cause of acute URTI of their children, 13 percent thought it was due to food, and only about 27 percent said it was caused by germs. Nearly 68 percent, 69 percent and 76 percent of them believed that antibiotics was helpful in treating the common cold, cough and fever, respectively. 29 percent of parents who thought that their child with acute URTI needed antibiotics were not prescribed with any. On the other hand, 17 percent believed that antibiotics were unnecessary when prescribed. 28 percent of parents had requested for antibiotics, and 93 percent received what they requested for their child with acute URTI. About 31 percent of parents who did not request any antibiotics claimed that private general practitioners habitually prescribed antibiotics. The antibiotic compliance was poor with only 74 percent completing the entire course, with 85 percent of them stopping once they improved symptomatically. 15 percent of parents gave "leftover" antibiotics, 24 percent gave "shared" antibiotics, and 5.5 percent bought antibiotics for their child with acute URTI without consulting a doctor. CONCLUSION: This study shows that parents often have inadequate knowledge and misconceptions on antibiotic use for acute URTI in children. Improved parental education may reduce unnecessary antibiotic prescription and antimicrobial resistance in the community.

Acute Disease↗

Type 2 diabetes mellitus with hypertension at primary healthcare level in Malaysia: are they managed according to guidelines?

INTRODUCTION: A study was conducted at primary healthcare level in the Melaka Tengah district of Malaysia to determine whether hypertension in patients with type 2 diabetes mellitus were managed according to guidelines. METHODS: A cross-sectional study involving 517 patients with diabetes mellitus from August to October 2003 was performed. RESULTS: All the subjects had type 2 diabetes mellitus. 350 (67.7 percent) patients had hypertension and about 25.7 percent of them were associated with microalbuminuria. The Malay ethnic group form the majority (54.6 percent), followed by Chinese (37.7 percent) and Indian (7.4 percent). Only 11 (3.1 percent) patients with type 2 diabetes mellitus and hypertension achieved the target blood pressure of less than 130/80 mmHg. For those who had not achieved the target goal, 39.5 percent of them were not on any antihypertensive drugs. 38.6 percent were on monotherapy and only 21.8 percent were on two or more antihypertensive drugs. Metoprolol was the most commonly used antihypertensive drug (22.4 percent), followed by Nifedipine (16.2 percent) and Prazosin (13.5 percent). Only 18.3 percent of patients with type 2 diabetes mellitus and hypertension were prescribed with angiotensin converting enzyme (ACE) inhibitors and 0.3 percent with angiotensin receptor blockers. For patients with type 2 diabetes mellitus, hypertension and microalbuminuria, only 14.1 percent of them were prescribed with ACE inhibitors. CONCLUSION: A significant proportion of patients with type 2 diabetes mellitus had associated hypertension but they were not managed optimally according to guidelines. More intensive management of hypertension among patients with diabetes is essential to reduce the morbidity and mortality at primary healthcare level.

Adult↗

Primary care doctors' perceptions towards evidence-based medicine in Melaka State: a questionnaire study.

A cross sectional study using a self-administered questionnaire to determine the perceptions of primary care doctors towards evidence-based medicine (EBM) was conclucted in Melaka state. About 78% of the primary care doctors were aware of EBM and agreed it could improve patient care. Only 6.7% of them had ever conducted a Medline literature search. They had a low level of awareness of review publications and databases relevant to EBM; only about 33% of them were aware of the Cochrane Database of Systemic Reviews. Over half of the respondents had at least some understanding of the technical terms used in EBM. Ninety percent of the respondents had Internet access and the majority of them used it at home. The main barriers to practicing EBM were lack of personal time and lack of Internet access in the primary care clinics.

Adult↗

Management of type 2 diabetes mellitus: is it in accordance with the guidelines?

A cross-sectional study was conducted among 517 patients with diabetes mellitus at all health centres in Melaka Tengah District to examine whether these patients and their associated cardiovascular risk factors were managed according to current guidelines. All patients had Type 2 diabetes mellitus with mean age of 57.9 +/- 10.5 years and the mean duration of diabetes was 7.2 +/- 6.0 years. The glycaemic control was poor with 53.6% of the patients having HbAlc above 8% (mean = 8.5%) and 24% of them had microalbuminuria. Among these patients with poor glycaemic control, about 47.6% of them were on monotherapy. Three hundred and fifty (67.7%) patients had hypertension but only 11 (3.1%) achieved target blood pressure of less than 130/80 mmHg. Only 18.3% of the diabetics with hypertension were prescribed angiotensin converting enzyme inhibitors and 0.3% with angiotensin receptor blockers. Nearly two-third of them had low-density lipoprotein cholesterol greater than 2.6 mmol/l (mean = 3.4 mmol/l) but only 6.8% were prescribed lipid-lowering agents. Aspirin was prescribed to 8.2% of diabetics aged above 40 years. Sixteen percent of the patients smoked, 53% did not do any exercise, and the mean BMI was 26.8 kg/mn. The management of diabetes mellitus and its associated cardiovascular risk factors was suboptimal on the basis of current clinical guidelines. A greater effort in educating doctors in the health centres about these management and adherence to the guidelines is important in reducing patients' risk of cardiovascular disease and its associated morbidity and mortality.

Adult↗

Human endothelin converting enzyme-2 (ECE2): characterization of mRNA species and chromosomal localization.

Generation of the functionally pleiotropic members of the endothelin vasoactive peptide family is critically catalyzed by unique type II metalloproteases, termed endothelin converting enzymes (ECE). Isolation of human ECE-2 (EC 3.4.24.71) cDNAs revealed deduced open reading frames of 787 and 765 amino acids with approximately 60% identity with human ECE-1. Characterization of mRNA variants revealed mRNA structural diversity at the 5'-terminus. Two mRNA species exist containing distinct first and second exons. Furthermore, in one of these species, an in-frame deletion of the intracytoplasmic domain removed 29 amino acids. Because of the previously reported human genetic diseases ascribed to germline mutations of member genes of the endothelin family, ECE2 was localized in human chromosomes with fluorescence in situ hybridization and radiation hybrid mapping to 3q28-q29 and SHGC-20171/D3S1571, respectively.

Adrenal Glands↗

Solid-cystic papillary tumor of the pancreas in children.

Solid-cystic papillary tumor (SCPT) of the pancreas is a rare neoplasm in children. The current study attempted to estimate the incidence and possible pathological origin of the tumor. Clinicopathologic features of the children under the age of 16 years with pancreatic tumors managed in a single institution between January 1993 and November 1999 were reviewed. Representative blocks of SCPT specimens were immunostained for neuron-specific enolase (NSE) chromogrannin, synaptophysin, insulin, glucagon, somatostatin, and gastrin. There were three SCPTs, two pancreatic endocrine tumors, and one acinar cell carcinoma during the study period. The estimated yearly incidence in the referral area of 2 million population is about 0.01 pediatric SCPT per year per 100,000 population. The children underwent surgical removal of the tumors. Postoperatively, they were followed up for 6 months to 4 years and were well. Immunostaining for NSE, chromogranin, synaptophysin, insulin, somatostatin, and gastrin was negative in all cases. SCPT may thus be the most common pancreatic tumor in the Asian pediatric population. The pathological origin of the tumor remains unclear and requires further investigations.

Adolescent↗

Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia.

t(1;22) is the principal translocation of acute megakaryoblastic leukemias. Here we show this chromosomal rearrangement to result in the fusion of two novel genes, RNA-binding motif protein-15 (RBM15), an RNA recognition motif-encoding gene with homology to Drosophila spen, and Megakaryoblastic Leukemia-1 (MKL1), a gene encoding an SAP (SAF-A/B, Acinus and PIAS) DNA-binding domain.

Chromosomes, Human, Pair 1↗

Successful mismatched sibling cord blood transplant in Hb Bart's disease.

A 20-month-old girl with Hb Bart's disease, who had survived neonatal complications, underwent HLA-DR antigen mismatched sibling cord blood transplantation successfully. Immune thrombocytopenia, which occurred around 2.5 months after transplant, responded to intravenous gamma-globulin. The fetal hemoglobin level rose to a peak of 52.3% on day +69 post transplant and declined gradually during the following year. Ten percent of hemoglobin Bart's was detected 2 months after transplant and this reflects the alpha-thalassemia trait of the donor.

Female↗

Characterization of additional genetic events in childhood acute lymphoblastic leukemia with TEL/AML1 gene fusion: a molecular cytogenetics study.

TEL/AML1 gene fusion that results from a cryptic t(12;21) is the most common genetic aberration in childhood B-lineage acute lymphoblastic leukemia (ALL). While the translocation may initiate the leukemic process, critical secondary genetic events are currently believed to be pivotal for leukemogenesis. We investigated 12 cases of childhood ALL with TEL/AML1 gene fusion by fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) and documented additional or secondary genetic changes in seven patients (58%). Three patients showed extra copies of chromosome 21 including a case in which the trisomy 21 (+21) clone was distinct from the one harboring TEL/AML1 gene fusion. Interestingly, one patient without +21 showed amplification of the AML1 gene on chromosome 21q, supporting the contention that AML1 amplification may be an important additional genetic event. Gene expression study by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) in two of these four patients showed an increase in AML1 transcripts that paralleled the increase in gene copy number. Deletion of the normal TEL allele was detected in two patients, with one of them showing loss of chromosome 12 together with duplication of the der(12)t(12;21). Finally, one patient showed duplication of the fusion signal. Our findings confirm that additional or secondary genetic changes including AML1 amplification are commonly encountered in childhood ALL with TEL/AML1 gene fusion, which are envisaged to play significant roles in disease progression.

Adolescent↗

DNA elements of the type 1 adenylyl cyclase gene locus enhance reporter gene expression in neurons and pinealocytes.

The Ca2+-stimulated type 1 adenylyl cyclase (AC1) contributes to several forms of synaptic plasticity and is the only known neurospecific adenylyl cyclase. Furthermore, the protein and mRNA levels of AC1 undergo a circadian oscillation in the pineal gland, and AC1 may play a pivotal role in regulating nocturnal melatonin synthesis. To better understand the expression of AC1, we isolated mouse genomic DNA clones of AC1. The transcription and translation start regions of mouse AC1 share extensive homologies with the bovine counterpart. The upstream proximal region has potential binding sites for transcription factors, including the steroid receptor family, the E-box factors, and Sp1. A 280-bp fragment that contains the transcription start site directed reporter gene expression in cultured cortical neurons and pinealocytes functioning as a basal neuro- and pineal-directed promoter. Interestingly, pinealocyte expression of the reporter gene was inhibited by increases in cAMP. This cAMP sensitivity may explain why AC1 mRNA in the pineal is low at night when cAMP is elevated and high during the day when cAMP signals drop. An adjacent 330-bp fragment interacted specifically with nuclear factor(s) that we designate binary E-box factor (BEF). Methylation interference and DNase I footprinting identified the BEF-binding site sequence as 5'-CCAAGGTCACGTGGC-3'. When linked to the basal tissue-directed promoter, this 15-bp sequence further enhanced reporter expression in neurons and pinealocytes. We propose that this 15-bp sequence may contribute to increased expression of AC1 in neurons and pinealocytes relative to other cells.

Adenylyl Cyclases↗

Ewing sarcoma of the small intestine.

This report describes a rare case of Ewing sarcoma (ES) of the small intestine. The patient was a 9-year-old girl with progressive abdominal distension. Computed tomography showed a large mass in the small bowel. Histopathologic examination of the resected tumor showed ES with typical histologic, immunohistochemical, and ultrastructural features. The tumor recurred in the pelvic cavity 18 months after the original surgery. Molecular study of the recurrent tumor confirmed a diagnostic EWS-FLI1 gene fusion. This patient illustrates the unique occurrence of ES in the small intestine.

Child↗