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Biomedical subjects

S K Ng

Publications and source records attributed to S K Ng.

At least 19 recordsLinked to original sources
PubMed2006

A mixture model with random-effects components for clustering correlated gene-expression profiles.

MOTIVATION: The clustering of gene profiles across some experimental conditions of interest contributes significantly to the elucidation of unknown gene function, the validation of gene discoveries and the interpretation of biological processes. However, this clustering problem is not straightforward as the profiles of the genes are not all independently distributed and the expression levels may have been obtained from an experimental design involving replicated arrays. Ignoring the dependence between the gene profiles and the structure of the replicated data can result in important sources of variability in the experiments being overlooked in the analysis, with the consequent possibility of misleading inferences being made. We propose a random-effects model that provides a unified approach to the clustering of genes with correlated expression levels measured in a wide variety of experimental situations. Our model is an extension of the normal mixture model to account for the correlations between the gene profiles and to enable covariate information to be incorporated into the clustering process. Hence the model is applicable to longitudinal studies with or without replication, for example, time-course experiments by using time as a covariate, and to cross-sectional experiments by using categorical covariates to represent the different experimental classes. RESULTS: We show that our random-effects model can be fitted by maximum likelihood via the EM algorithm for which the E(expectation)and M(maximization) steps can be implemented in closed form. Hence our model can be fitted deterministically without the need for time-consuming Monte Carlo approximations. The effectiveness of our model-based procedure for the clustering of correlated gene profiles is demonstrated on three real datasets, representing typical microarray experimental designs, covering time-course, repeated-measurement and cross-sectional data. In these examples, relevant clusters of the genes are obtained, which are supported by existing gene-function annotation. A synthetic dataset is considered too. AVAILABILITY: A Fortran program blue called EMMIX-WIRE (EM-based MIXture analysis WIth Random Effects) is available on request from the corresponding author.

Algorithms↗
PubMed2005

Autosomal dominant familial chronic mucocutaneous candidiasis associated with acne rosacea.

INTRODUCTION: Autosomal dominant chronic mucocutaneous candidiasis (CMC) without endocrinopathy (OMIM 114580) is a well-described entity. The associations recorded with this disorder to date are intercellular adhesion molecule-1 (ICAM-1) deficiency and hyper-immunoglobulin E syndrome. CLINICAL PICTURE: We report a new association in a family (mother and nonidentical twin sons) where acne rosacea is a prominent feature together with CMC. In addition, antibodies to thyroid microsomal and antiparietal cell were also isolated. The autoantibodies might be associated with a current "latent" endocrinopathy in particular autoimmune thyroiditis. TREATMENT: The patient was treated with intermittent pulses of itraconazole for the candidiasis and doxycycline initially before being substituted with isotretinoin 6 months later for the rosacea. OUTCOME: The patient's candidiasis responded well and has been in remission for 3 months while his rosacea continues to improve.

Adult↗
PubMed2004

Modelling the distribution of ischaemic stroke-specific survival time using an EM-based mixture approach with random effects adjustment.

A two-component survival mixture model is proposed to analyse a set of ischaemic stroke-specific mortality data. The survival experience of stroke patients after index stroke may be described by a subpopulation of patients in the acute condition and another subpopulation of patients in the chronic phase. To adjust for the inherent correlation of observations due to random hospital effects, a mixture model of two survival functions with random effects is formulated. Assuming a Weibull hazard in both components, an EM algorithm is developed for the estimation of fixed effect parameters and variance components. A simulation study is conducted to assess the performance of the two-component survival mixture model estimators. Simulation results confirm the applicability of the proposed model in a small sample setting.

Age Factors↗
PubMed2004

Discovery of binding motif pairs from protein complex structural data and protein interaction sequence data.

Unravelling the underlying mechanisms of protein interactions requires knowledge about the interactions' binding sites. In this paper, we use a novel concept, binding motif pairs, to describe binding sites. A binding motif pair consists of two motifs each derived from one side of the binding protein sequences. The discovery is a directed approach that uses a combination of two data sources: 3-D structures of protein complexes and sequences of interacting proteins. We first extract maximal contact segment pairs from the protein complexes' structural data. We then use these segment pairs as templates to sub-group the interacting protein sequence dataset, and conduct an iterative refinement to derive significant binding motif pairs. This combination approach is efficient in handling large datasets of protein interactions. From a dataset of 78,390 protein interactions, we have discovered 896 significant binding motif pairs. The discovered motif pairs include many novel motif pairs as well as motifs that agree well with experimentally validated patterns in the literature.

Amino Acid Motifs↗
PubMed2004

Does the presence of a tracheal bronchus affect the margin of safety of double-lumen tube placement?

During double-lumen tube (DLT) placement, the anesthesiologist must be mindful of the margin of safety. We determined how this margin is affected by the presence of a tracheal bronchus by elucidating the mathematical relationship between some relevant physical dimensions of the trachea, bronchi, and DLT. Our results suggest that a tracheal bronchus only rarely affects the intrinsic margin of safety of DLT placement. When the tracheal bronchus is located much higher than its most frequently seen location (within 2 cm from the carina), however, there is increased risk that it could be blocked by the tracheal cuff of a left-sided DLT.

Bronchi↗
PubMed2004

A case of nephrogenic fibrosing dermopathy.

INTRODUCTION: Nephrogenic fibrosing dermopathy is a recently recognised fibrosing disorder originally identified as a scleromyxoedema-like cutaneous disease in patients with renal disease. CLINICAL PICTURE: A 45-year-old lady with systemic lupus erythematosus presented with well-defined erythematous, non-tender, indurated plaques on both legs 4 months after haemodialysis for rapidly progressive glomerulonephritis and acute renal failure. Skin biopsy showed dermal fibrosis with increased proliferation of dermal fibroblasts and collagen bundles separated by clefts. There were increased dermal deposits of mucin and an increase in elastic fibres. TREATMENT AND OUTCOME: Haemodialysis was instituted for 2 weeks followed by monthly intravenous cyclophosphamide. Skin lesions remained unchanged 8 months later despite normalisation of renal function. CONCLUSION: Nephrogenic fibrosing dermopathy appears to be a definite new entity in patients with underlying renal insufficiency. Further multi-centre collaborative study is necessary to identify the prevalence, cause, treatment and prognosis of this disorder.

Acute Kidney Injury↗
PubMed2004

Cutaneous Mycobacterium haemophilum infections in immunocompromised patients in a dermatology clinic in Singapore.

INTRODUCTION: Mycobacterium haemophilum, a nontuberculous mycobacterium (NTM) that was first described in 1978, is a pathogen that can cause an array of symptoms in immunocompromised patients, predominantly cutaneous. CLINICAL PICTURE: We report our hospital's experience with the first 3 patients diagnosed with this infection from 1994 to 2002. All were women; one had systemic lupus erythematosus (SLE), one had mycosis fungoides and the last had Sjogren's syndrome with recurrent bacterial infections, although the specific nature of her immunocompromised state has not been defined. All were HIV negative. All 3 women presented with cutaneous lesions--the first with recurrent erythematous plaques on the limbs and back, the second with tender nodules and abscesses on the knees, and the third with papular eruptions on the cheek. TREATMENT/OUTCOME: All responded to a combination of antibiotics and are presently still undergoing treatment and follow-up. CONCLUSION: Infections caused by M. haemophilum occur mainly in immunocompromised patients. They can present with a variety of cutaneous manifestations, which require a high index of suspicion and coordination between the treating physician and the laboratory for diagnosis. Combination antibiotic treatment is recommended, and patients should be followed up after treatment to survey for possible relapse.

Adult↗
PubMed2003

An EM-based semi-parametric mixture model approach to the regression analysis of competing-risks data.

We consider a mixture model approach to the regression analysis of competing-risks data. Attention is focused on inference concerning the effects of factors on both the probability of occurrence and the hazard rate conditional on each of the failure types. These two quantities are specified in the mixture model using the logistic model and the proportional hazards model, respectively. We propose a semi-parametric mixture method to estimate the logistic and regression coefficients jointly, whereby the component-baseline hazard functions are completely unspecified. Estimation is based on maximum likelihood on the basis of the full likelihood, implemented via an expectation-conditional maximization (ECM) algorithm. Simulation studies are performed to compare the performance of the proposed semi-parametric method with a fully parametric mixture approach. The results show that when the component-baseline hazard is monotonic increasing, the semi-parametric and fully parametric mixture approaches are comparable for mildly and moderately censored samples. When the component-baseline hazard is not monotonic increasing, the semi-parametric method consistently provides less biased estimates than a fully parametric approach and is comparable in efficiency in the estimation of the parameters for all levels of censoring. The methods are illustrated using a real data set of prostate cancer patients treated with different dosages of the drug diethylstilbestrol.

Algorithms↗
PubMed2003

Treatment of toxic epidermal necrolysis in AIDS with intravenous immunoglobulins.

Individuals with AIDS are at higher risk of developing severe cutaneous adverse drug reactions. We report two AIDS patients with drug-induced toxic epidermal necrolysis (TEN). The suspected drugs were discontinued. Both patients were treated with intravenous human immunoglobulins at a dose of 1 g/kg body weight per day for two consecutive days and both experienced a good outcome. Intravenous immunoglobulin potentially lowers the morbidity and mortality of TEN and shortens the duration of the patient's hospitalization.

Acquired Immunodeficiency Syndrome↗
PubMed2003

A case of penicillamine-induced dermopathy.

INTRODUCTION: We describe an interesting patient with penicillamine-induced dermopathy. CLINICAL PICTURE: A 49-year-old woman presented with a 1-year history of recurrent haemorrhagic blisters, milia and purpura over both her elbows, while on long-term penicillamine therapy (1.5 g daily) for Wilson's disease. Histologically, dermal elastin fibres were markedly reduced in the affected areas, consistent with penicillamine-induced elastolysis. TREATMENT AND OUTCOME: The patient's lesions improved significantly after reduction of her penicillamine dose to 500 mg daily. CONCLUSIONS: The cutaneous side effects of long-term penicillamine therapy are important to recognise as they may be associated with significant morbidity and may be markers of more ominous underlying systemic elastic fibre damage.

Biopsy, Needle↗
PubMed2002

A case of neonatal stridor.

A case is reported of a retropharyngeal abscess in a neonate who presented with increasing stridor since birth. Group B streptococcus was cultured from the abscess contents and the maternal birth tract.

Anti-Bacterial Agents↗
PubMed2002

Allopurinol hypersensitivity syndrome and acute myocardial infarction--two case reports.

INTRODUCTION: Allopurinol hypersensitivity syndrome is an idiosyncratic drug reaction characterised by an acute and severe multiorgan disease. It usually begins 2 to 6 weeks after starting allopurinol. The most important and critical characteristics are the presence of visceral involvement and haematological abnormalities; hepatitis, interstitial nephritis and eosinophilia are most frequently seen. However, cardiac involvement has not been previously reported. CLINICAL PICTURE: Two previously well young Chinese men presented with fever, rash and hepatitis 3 weeks after taking allopurinol. The clinicopathological presentation was typical of allopurinol hypersensitivity syndrome. TREATMENT AND OUTCOME: Both men received systemic corticosteroid therapy and had full recovery. A few months later, they each had an acute myocardial infarction with a fatal outcome, despite minimal cardiac risk factors and no family history of coronary artery disease. CONCLUSION: The immunologic process in allopurinol hypersensitivity syndrome may have caused coronary vasculitis and subsequent myocardial infarct. Alternatively, the idiosyncratic reaction may have damaged myocardium, with the resultant myocarditis masquerading as coronary artery disease. Patients with allopurinol hypersensitivity syndrome should be followed up for cardiac involvement.

Adult↗
PubMed2001

The dental implications of chronic use of acidic medicines in medically compromised children.

OBJECTIVE: Liquid oral medicines form a significant proportion (11%) of the medicines used by the population as a whole, either prescribed or over the counter. The active agent, as well as some of the other ingredients, can pose a threat to oral health. METHOD: Eight liquid oral medicines and two effervescent preparations routinely prescribed for long-term use by paediatric renal patients were assessed for titratable acidity and pH values. RESULTS: All of the medicines tested were acidic and the majority were well below the critical pH of 5.5 at which enamel demineralisation takes place. The titratable acidity values, at a pH of 6.7, ranged between 0.01 and 1.54 for the liquid preparations but were 8.4 and 10.6 for the two effervescent tablets tested. CONCLUSION: Surplus acid in effervescent preparations while ensuring palatability of medicines and thus compliance, may produce unwanted dental side effects in children who are already medically compromised.

Acids↗