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Biomedical subjects

I Ng

Publications and source records attributed to I Ng.

At least 37 records · Page 2Linked to original sources
PubMed2000

An anemic patient with phenotypical beta-thalassemic trait has elevated level of structurally normal beta-globin mRNA in reticulocytes.

Of the numerous beta-thalassemic mutations linked or unlinked to the beta-globin gene, all invariably cause a decrease in or an absence of structurally normal beta-globin mRNA when assayed. Here we report an anemic patient with an elevated alpha-/beta globin synthesis ratio of 2.0 in his reticulocytes. The patient's blood film showed marked red cell anisopoikilocytosis, microcytosis, and hypochromia, consistent with a typical beta-thalassemic trait phenotype. Acid-eluted erythrocytes contained numerous Heinz bodies. Molecular analysis of the patient's reticulocyte mRNA indicated that, compared to normal controls, there was a 3-fold elevation of beta-globin mRNA when assayed by RT-PCR and a 1.5-fold elevation of beta-globin mRNA when assayed by RNA slot blotting. The level of alpha-globin mRNA was normal when compared to that of normal adult controls. Extensive structural analysis of the beta-globin mRNA and gene by sequencing of RT-PCR and PCR products, respectively, did not detect any mutations. Tryptic mapping of purified beta-globin chains also did not show any abnormal tryptic fragments. These data indicated that a relative insufficiency of structurally normal beta-globin mRNA was not a cause of this beta-thalassemic phenotype. Therefore, the lesion that caused this particular thalassemic phenotype is not linked to the beta-globin allele.

Anemia↗
PubMed2000

Apoptosis occurs after cerebral contusions in humans.

OBJECTIVE: Animal model systems have shown that head trauma can induce cell death in regions of the brain away from the site of the impact via a process of apoptosis. We sought to determine whether there was evidence of cellular apoptosis in clinically collected materials from human head trauma patients, as well as to attempt to determine the pathway by which it may occur. METHODS: Thirty-one sequential specimens of brain tissue excised during emergency craniotomy for evacuation of cerebral contusions with mass effect were examined. Non-necrotic pericontusional tissues were detected in 11 samples. These were examined for the presence of apoptotic cells by the terminal deoxynucleotide transferase-mediated nick end labeling method as well as by immunohistochemistry to detect possible expression of the apoptosis-related genes p53, bcl-2, and bax. RESULTS: Bax expression was detected in all patients, whereas bcl-2 expression was noted in six patients. Terminal deoxynucleotide transferase-mediated nick end labeling-positive cells were noted in eight patients. One instance of p53-positive immunostaining was observed. Patients with bcl-2 expression had a better survival rate than patients in whom no bcl-2 expression was noted (P = 0.01). CONCLUSION: Although necrosis seemed to be the main finding in cerebral contusions, these results support the hypothesis that apoptosis does occur in patients after traumatic brain injury, and this may contribute to the secondary injury processes that are seen with head injury. Patients in whom anti-apoptotic bcl-2 is induced seem to have a better prognosis. This may have important clinical significance in the development of bcl-2 homologs or bax inhibitors to prevent apoptosis.

Adult↗
PubMed2000

Spinocerebellar ataxia in Singapore: predictive features of a positive DNA test?

Significant differences in frequency of the different spinocerebellar ataxia (SCA) subtypes have been described to occur in different populations. A 'blunderbuss' diagnostic DNA testing approach would entail unnecessary healthcare cost. In this study, we determine the prevalence of SCA subtypes and predictive features of a positive DNA test in consecutive clinically diagnosed SCA cases in Singapore. Twenty-one consecutive patients from 14 families were evaluated over a 3-year period. Thirteen patients (61.9%) from 6 families had a positive DNA test. Eleven of these (all ethnic Chinese) had SCA 3 (abnormal CAG size ranged from 61 to 71), and 2 ethnic Malays had SCA 2 (abnormal CAG size of 39). Clinical features which were highly predictive of a positive DNA SCA test in our population included presence of a positive family history, chorea and dystonia, muscle and tongue fasciculations, gaze-evoked nystagmus, and hypertonia. Our study draws attention to the observation that knowledge of relatively specific features of the most common SCA subtype in a local population can greatly enhance the practical accuracy of the choice of which SCA DNA test to order.

Adult↗
PubMed1999

Role of genomic rearrangements in producing new ribotypes of Salmonella typhi.

Salmonella typhi is the only species of Salmonella which grows exclusively in humans, in whom it causes enteric typhoid fever. Strains of S. typhi show very little variation in electrophoretic types, restriction fragment length polymorphisms, cell envelope proteins, and intervening sequences, but the same strains are very heterogeneous for ribotypes which are detected with the restriction endonuclease PstI. In addition, the genome of S. typhi has been proven to undergo genomic rearrangement due to homologous recombination between the seven copies of rrn genes. The relationship between ribotype heterogeneity and genomic rearrangement was investigated. Strains of S. typhi which belong to 23 different genome types were analyzed by ribotyping. A limited number of ribotypes were found within the same genome type group; e. g., most strains of genome type 3 belonged to only two different ribotypes, which result from recombination between rrnH and rrnG operons. Different genome type groups normally have different ribotypes. The size and identity of the PstI fragment containing each of the seven different rrn operons from S. typhi Ty2 were determined, and from these data, one can infer how genomic rearrangement forms new ribotypes. It is postulated that genomic rearrangement, rather than mutation, is largely responsible for producing the ribotype heterogeneity in S. typhi.

Bacterial Typing Techniques↗
PubMed1999

Decision analytic approach to severe head injury management.

Severe head injury management in the intensive care unit is extremely challenging due to the complex domain, the uncertain intervention efficacies, and the time-critical setting. We adopt a decision analytic approach to automate the management process. We document our experience in building a simplified influence diagram that involves about 3000 numerical parameters. We identify the inherent problems in structuring a model with unclear domain relationships, numerous interacting variables, and real-time multiple inputs. We analyze the effectiveness and limitations of the decision analytic approach and present a set of desiderata for effective knowledge acquisition in this setting. We also propose a semi-qualitative approach to parameter elicitation.

Craniocerebral Trauma↗
PubMed1999

Young Investigator's Award: induction of apoptosis following traumatic head injury in humans.

Apoptosis or programmed cell death plays an important role in many developmental and pathological processes of the central nervous system. In head injury, apoptosis has been recently implicated in many studies on animal brain samples the phenomenon of apoptotic gene expression (bax and bcl-2). Twenty specimens of contused brain tissue (temporal and frontal lobe) from 20 patients who underwent emergency craniotomy and removal of mass lesions were obtained from May to October 1997. The samples collected were immediately snap frozen in liquid nitrogen and stored at -80 degrees C. Immunohistochemical analysis was performed to detect the expression of bcl-2, bax and p53 using standard avidin-biotin complex second antibody conjugate methodology utilising commercially available primary and secondary antibodies. The average age of cohort was 46.24 +/- 22.17 years, the average Glasgow Coma Scale on admission was 9.19 +/- 4.72, and the average duration from injury to collection of the sample was 20.62 +/- 40.57 hours. There was documented hypoxia and hypotension seen in 5 of the 20 patients (25%). Significant levels of bax protein expression were noted in all samples, and p53 expression in 30% of samples. No bcl-2 expression was observed. Our study showed that for the first time the strong expression of the pro-apoptotic gene (bax) and low levels of the anti-apoptotic gene (bcl-2), thus implicating the mechanism of apoptosis in brain injury following trauma. The use of agents to inhibit apoptosis may be beneficial in head injury patients.

Apoptosis↗
PubMed1998

Outcome of patients with traumatic brain injury managed on a standardised head injury protocol.

A standardised protocol in the management of severe head injury in our hospital enables pre-determined critical care-paths and consistent treatment regimes to be instituted. In Singapore there has been no previously reported data on the outcome of severely head injured patients. Over a 6-month period, 48 consecutive patients who were enrolled in our severe head injury protocol were prospectively studied. In addition to demographic and outcome data, physiologic measurements obtained from a computerised patient information system (Carevue Hewlett-Packard 9000) were analysed to determine the mean cerebral perfusion pressure (CPP) and intracranial pressure (ICP) achieved throughout the protocol period. Median Glasgow Coma Score for all patients on admission to the protocol was 6 (range 4 to 8). The mean age was 34.46 +/- 15.03 years with a male to female ratio of 43:5. The average duration of treatment on the protocol was 110.73 hours. Initial ICP measured was 25.5 +/- 19.68 mmHg. Outcome was measured at 6 months post-injury using the Glasgow Outcome Score. Favourable outcome (GOS 4-5) was seen in 29 of 48 patients (60.4%) while 12 out of 48 (25%) had an unfavourable outcome. There was a mortality of 14.6% (7 of 48 patients). Patients who survived had a higher mean CPP (P = 0.00005), a lower initial ICP and a mean ICP (P = 0.007 and 0.0009). The use of a protocol with standardised treatment goals in the management of traumatic brain injury allows for the optimal use of limited resources and provides consistency in treatment. Good outcome is related to early aggressive resuscitation to prevent hypotension and hypoxia, prompt evacuation of surgical mass lesions and the maintenance of an adequate cerebral perfusion pressure. Our results are comparable with that reported in other established neurotrauma systems.

Accidents↗
PubMed1997

Loss of c-met protooncogene in primary and metastatic sites of breast cancer.

BACKGROUND: It has been proposed that clones of tumor cells acquire higher metastatic potential as a result of specific genetic alterations. This study was designed to determine the role of the c-met protooncogene in systemic spread by comparing the loss of the c-met protooncogene between primary and metastatic breast carcinomas. METHODS: Only patients who had not received chemotherapy or radiotherapy in the preceding 6 months were included in this study. Histologically proven malignant tissue was obtained from the primary tumor, involved nodes, and distant metastatic and recurrent tumors of patients with breast carcinomas. Allelic loss of the c-met protooncogene in tumor tissue was determined by Southern blotting using a polymerase chain reaction-generated 347-bp human met-H probe. Restriction digestion was performed using Taq I and Msp I, with the patient's lymphocyte DNA as controls. RESULTS: Of 52 patients, lymphocyte DNA from 36 patients was heterozygous for the c-met protooncogene (69% informative). Forty-six tumors from these 36 patients were analyzed. Four of 30 primary tumors (13%) showed allelic loss of c-met. Of the nine nodal metastases examined, three (33%) showed allelic loss of the c-met protooncogene. Of seven distant metastatic breast tumors or recurrent disease, two (29%) showed allelic loss (both in patients with skin metastasis in the chest wall). CONCLUSIONS: Allelic loss of the c-met protooncogene was detected in both primary (13%) and metastatic sites (31%) of breast cancer. Although a higher proportion of allelic loss of c-met was noted in nodal and distant/recurrent disease, the difference when compared with the primary tumor was not statistically significant. These findings indicate a limited role of the c-met protooncogene in breast cancer metastases.

Adult↗
PubMed1997

Closed head injuries in children following the use of a sarong cradle.

INTRODUCTION: Sarong cradles are unique to South-East Asian culture. Their use can lead to injuries from falls, over-enthusiastic rocking and defective equipment. We present 19 children who attended the Accident and Emergency (A&E) Department of a general hospital and who sustained injuries while in a sarong cradle. All had closed head injuries. METHODS AND MATERIALS: The data was collected over a 9-month period from September 1992 to May 1993. All patients with a documented history of fall following the use of a sarong cradle, were recruited into the study. The adults accompanying the patients were interviewed with a structured questionnaire. The information was recorded by the doctor in attendance. RESULTS: The ages of the 19 patients ranged from 13 days to 29 months. There were 17 Chinese, 1 Malay and 1 Indian. The types of closed head injuries included minor head injury with no external signs of injury, scalp lacerations, scalp haematomas and severe head injury with an extradural haematoma. The majority (14) were discharged from the A&E Department with head injury advice, 4 were admitted to the General Neurosurgical ward and one, to the Neurosurgical Intensive Care Unit. There were no fatalities in this group. The accidents happened while the children were either sleeping (14), playing (4) or feeding (1). CONCLUSIONS: While most head injuries sustained in this manner are usually mild, there is a potential that such injuries may lead to more serious injuries. Care givers who use the sarong cradle should be aware of the dangers and exercise due care during use.

Accidental Falls↗
PubMed1996

Clinical and histological features of gastric antral vascular ectasia: successful treatment with endoscopic laser therapy.

Gastric antral vascular ectasia is a rare but important cause of chronic gastrointestinal bleeding. We report five patients in whom endoscopic laser therapy successfully controlled repeated blood loss. The patients were elderly (age range: 61-84 years; mean age: 75 years) and three of them were female. Endoscopically, all patients presented with a characteristic antral appearance of either ecstatic vascular 'stripes' radiating out from the pylorus, or multiple cherry-red spots. In all patients, the gastric mucosal biopsy specimens showed dilatation of the capillaries with focal fibrin thrombi and fibromuscular hyperplasia. Marked improvement of both endoscopic and histological features was achieved with endoscopic laser treatment using Nd-YAG laser photocoagulation. Its importance lies in its recognition and successful treatment with endoscopic laser therapy, which offers an effective and relatively safe alternative to surgery, particularly in elderly patients.

Aged↗
PubMed1996

Relation of hormone and menopausal status to outcomes following excimer laser photorefractive keratectomy in women. Melbourne Excimer Laser Group.

PURPOSE: To examine the effect of hormone use, pregnancy and menopausal status on clinical outcomes following excimer laser surgery for myopia and myopic astigmatism. METHODS: Participants comprised all female patients of the Melbourne Excimer Laser Group (MELG). A standardised surgical protocol was followed by the 27 MELG members, using the VisX 20/20 excimer laser and included the prospective collection of the following information preoperatively and one, three, six and 12 months after the procedure: uncorrected and best corrected visual acuity with a LogMAR chart; best manifest refraction; and subjective assessment of corneal clarity. A survey that elicited information about oral contraceptive (OC) use, pregnancy history, surgical and natural menopause, and use of hormone replacement therapy (HRT) was mailed to all the women. RESULTS: A 77% response to the mailed survey was achieved. Two women were pregnant at the time of surgery, one became pregnant during the first month after surgery, and all three women were excluded from further analyses, although a review of two of the case histories revealed suboptimal clinical outcomes. Women taking OC were included in the control group after OC use was shown not to be associated with outcome. Women were grouped accordingly: control, n = 225, pre-menopausal on HRT, n = 7, post-menopausal not on HRT, n = 34; and post-menopausal on HRT, n = 21. The groups differed significantly with regard to age and preoperative spherical equivalent. After controlling for age and preoperative spherical equivalent, the mean number of uncorrected LogMAR letters read one year after surgery was significantly lower for the post-menopausal women on the HRT in comparison with the control group. Best corrected acuity and corneal clarity were not significantly different among the groups. DISCUSSION: These preliminary results suggest that the interaction of menopausal and HRT status could decrease the effectiveness of PRK and PARK, but require confirmation with a further study in a prospective manner using objective measures of corneal epithelial healing and serum hormone levels.

Adult↗
PubMed1995

Inborn errors of metabolism in Singapore.

Between 1992 and 1994 the Paediatric Metabolic Centre screened 403 patients for inherited metabolic disease. Seventeen patients were diagnosed, including 7 with organic acidurias, 5 with mucopolysaccharidoses, 2 with amino acid disorders, 2 with carbohydrate disorders and 1 with hyperlipidaemia. The ethnic distribution of disorders in Singapore is compared with incidences reported by others in this part of the world. It is likely that further studies will indicate which diagnostic or screening tests would best serve this community.

Adolescent↗
PubMed1995

Pericentric inversion 9--incidence and clinical significance.

Pericentric inversion of the chromosome 9, inv(9)(p11q13), is such a common occurrence that some cytogeneticists would consider them as normal variants. The incidence is said to be about 1% to 1.65% in the general population. Despite being categorised as a minor chromosomal rearrangement which does not correlate with abnormal phenotypes, many reports in the literature raised conflicting views regarding the association with subfertility and recurrent abortions, abnormal clinical conditions, as well as chromosomal abnormalities arising as a result of having this inversion. We studied the incidence and clinical significance of inv(9)(p11q13) patients retrospectively from 2448 antenatal cytogenetic analysis and 1058 peripheral blood karyotype collected over a 3-year period. Thirty cases of inv(9)(p11q13) from 29 families were found from the antenatal group, which gave an incidence of 1.2% and 6 cases from the peripheral blood karyotype analysis (incidence of 0.6%). The parental origin of the inv(9)(p11q13) in the antenatal group was of equal proportion and there was also no sex predilection for the fetuses carrying the inversion. The babies with the inversion were born with no phenotypic abnormalities. The 6 cases picked up from the peripheral blood karyotype analysis were 2 cases of paediatric patients with associated chromosomal abnormalities (one Trisomy 21 and the other del 13(q22q32)) and 4 adult patients with obstetric and fertility problems. The incidence of subfertility (36%) appeared to be high amongst the adult patients with inv(9)(p11q13). This may represent a true reflection of subfertility in inv(9)(p11q13) patients or a selective bias towards the older subfertile women who conceive at a later age and thus utilising the antenatal diagnostic setup.

Abortion, Habitual↗
PubMed1994

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↗