Search PubMed⌕ Search

Biomedical subjects

A Balakrishnan

Publications and source records attributed to A Balakrishnan.

At least 19 recordsLinked to original sources
PubMed2006

Auditory neuropathy/auditory dys-synchrony detected by universal newborn hearing screening.

The implementation of neonatal hearing screening has enabled early detection and intervention in hearing loss. The use of otoacoustic emissions (OAE) and auditory brainstem response testing in universal screening has led to the recognition of this recently described disorder called auditory neuropathy/auditory dys-synchrony (AN/AD). This diagnosis indicates that the infant has significant hearing loss despite having normal outer hair cells in the cochlea. We reviewed the characteristics and natural history of nine infants detected to have AN/AD from universal newborn hearing screening in a national pediatric hospital. Fifty-two cases of hearing loss were detected from 14,807 consecutively screened cases. Of the 52 cases, 9 had electrophysiological test results consistent with AN/AD. They include both premature infants who had major neonatal complications and term infants with no perinatal complications. Six cases had bilateral and three cases had unilateral findings. We suggest that AN/AD can occur in low-risk infants and hence screening of high-risk cases alone is insufficient. Our findings are discussed with reference to the current literature.

Evoked Potentials, Auditory, Brain Stem↗
PubMed2006

Operative workload of a paediatric otolaryngology department over a five-year period.

INTRODUCTION: The KK Women's and Children's Hospital (KKWCH) is Singapore's only tertiary institution dedicated wholly to the provision of healthcare for women and children. Since its opening in 1997, the clinical caseloads and the complexity of medical conditions managed by the various departments has increased considerably. This review aims to analyse the operative caseloads in the Department of Otolaryngology over five years from 2000 to 2004. METHODS: This is a retrospective review of the KKWCH Department of Otolaryngology operative records from year 2000 to 2004. The data on the type of operation and their frequency were collated, and the data are presented in a descriptive format. RESULTS: There was an increase in the number of operations performed from 656 in year 2000 to 1,148 in 2004, an increase of 75 percent. The increase in the staffing and operating clinical hours (in 2003 and 2004) plus the significant demand for paediatric otolaryngology service probably contributed to this increase. Tonsillectomy, with or without adenoidectomy, continues to be the most common procedure being performed in children, with myringotomy and tympanostomy tube insertion being the second commonest. Together, the ten most common operative procedures constitute 78.2 percent of all paediatric otolaryngological operative workload in the department over a five-year period. CONCLUSION: The data provided a review of the current pattern of otolaryngological surgical disease in the Singapore paediatric population, which may require operative intervention. Understanding and monitoring of this trend is important, as it allows the proper allocation of appropriate resources for the prevention and treatment of common paediatric surgical otolaryngological conditions.

Humans↗
PubMed2005

In vitro glucose uptake activity of Aegles marmelos and Syzygium cumini by activation of Glut-4, PI3 kinase and PPARgamma in L6 myotubes.

The purpose of the present study is to investigate the effect of methanolic extracts of Aegles marmelos and Syzygium cumini on a battery of targets glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPARgamma) and phosphatidylinositol 3' kinase (PI3 kinase) involved in glucose transport. A. marmelos and S. cumini are anti-diabetic medicinal plants being used in Indian traditional medicine. Different solvent extracts extracted sequentially were analysed for glucose uptake activity at each step and methanol extracts were found to be significantly active at 100ng/ml dose comparable with insulin and rosiglitazone. Elevation of Glut-4, PPARgamma and PI3 kinase by A. marmelos and S. cumini in association with glucose transport supported the up-regulation of glucose uptake. The inhibitory effect of cycloheximide on A. marmelos- and S. cumini-mediated glucose uptake suggested that new protein synthesis is required for the elevated glucose transport. Current observation concludes that methanolic extracts of A. marmelos and S. cumini activate glucose transport in a PI3 kinase-dependent fashion.

Aegle↗
PubMed2005

Inhibition of MAP kinases by crude extract and pure compound isolated from Commiphora mukul leads to down regulation of TNF-alpha, IL-1beta and IL-2.

The anti-inflammatory effect of the medicinal plant, Commiphora mukul gum was studied in peripheral blood mononuclear cells (PBMC). Bioassay-guided fractionation using conventional solvent extraction procedures, subsequent column fractionation, followed by monitoring specific activity in PBMC led to the isolation of a lead compound. Both crude ethyl acetate extract and the lead compound, thus isolated, showed inhibitory effect on proliferative response of PBMC in mitogenic lymphocyte proliferation and MLR assays. Further studies on inflammatory mediators such as IFN-gamma, IL-12, TNF-alpha, IL-1beta and NO showed down regulation, whereas no inhibition was observed in the case of anti-inflammatory cytokine IL-10. Immunoblot analysis revealed the inhibitory effect of crude ethyl acetate extract on phosphorylation of all the three mitogen activated protein kinases (MAPK) such as ERK, JNK and p38 MAPK. In contrast treatment with pure compound showed no inhibitory effect on ERK. c-fos and c-jun mRNA levels were also reduced in PMA stimulated cells on treatment with crude extract and pure compound. This reduction in c-fos and c-jun levels, when taken together with inhibition of MAPK activation, provides a possible mechanism by which both crude ethyl acetate extract and purified compound isolated from C. mukul exert its action.

Acetates↗
PubMed2005

Sensitization to dust mites in children with allergic rhinitis in Singapore: does it matter if you scratch while you sneeze?

BACKGROUND: Previously published data established Blomia tropicalis, as the major source of allergic sensitization in asthmatic children in tropical Singapore. Objective To define the prevalence, clinical characteristics and risk factors of species-specific mite sensitization in paediatric allergic rhinitis (AR) patients in this unique environment. METHODS: We performed a prospective evaluation of newly diagnosed AR patients, from 1 May 2003 to 30 April 2004, from the otolaryngology and allergy outpatient clinics of the Kendang Kerbau Children's Hospital in Singapore. Patients included in the study showed evidence of sensitization to at least one respiratory allergen source and completed a detailed questionnaire. Relative risk of sensitization and associated risk factors were calculated using logistic regression analysis with the forward stepwise model. Multivariate regression analysis was performed to adjust for confounding interactions. Continuous values were compared using anova, SPSS 9.0 for Windows (SPSS Inc., 1999). RESULTS: One hundred and seventy-five patients were included, 119 (68%) males, 142 (81%) Chinese, age mean 7.9 years (range 2-16). Sixty-eight patients (39%) reported a concomitant diagnosis and/or clinical complaints of bronchial asthma and 84 (48%) of atopic dermatitis. Skin prick test results were positive for traditional house dust mites (Dermatophagoides pteronyssinus. and D. farinae mix) in 85% of patients and for B. tropicalis in 62%. Overall mite sensitization was 98%, household pets 10%, moulds 9% and food proteins 12%. By far the single most significant factor associated with Dermatophagoides sensitization in this group was the presence of allergic eczema (odds ratio (OR) 31.8%, 95% confidence interval (CI) 3.6-285, P=0.002). Allergic eczema was negatively associated with B. tropicalis sensitization (OR 0.26%, 95% CI 0.14-0.5). CONCLUSIONS: Children with AR and concomitant atopic dermatitis show a preferential sensitization to the Dermatophagoides mites. In our population, B. tropicalis sensitization is more prominent in children with pure respiratory allergy.

Adolescent↗
PubMed2003

Treatment of urinary tract infection with gentamicin once or three times daily.

AIM: To examine the safety and efficacy of once-daily (OD) gentamicin treatment compared with conventional 8-hourly dosing (TDS) for urinary tract infection (UTI). METHODS: This was a prospective, randomized, controlled trial of children 1 mo to 13 y of age with presumed UTI. Children were randomly assigned to OD gentamicin 5 mg kg(-1) d(-1) or TDS gentamicin 6 mg kg(-1) d(-1) divided 8 hourly. Microbiological efficacy, nephrotoxicity, ototoxicity and renal scarring were assessed at the end of treatment. RESULTS: 210 patients with presumed UTI were recruited, of whom 172 were analysable (OD 84, TDS 88). The median age was 7 mo, 50% were male and 74% (n = 127) of patients had pyelonephritis. The majority of infections were due to Escherichia coli (n = 153, 89%), of which 9 (5.2%) were bacteraemic. Comparing the two groups, there was no significant difference in age, gender, duration of fever before admission, pyuria, nitrite positivity or initial total white blood cell count. All patients had negative urine cultures after 2-3 d of treatment, demonstrating 100% microbiological efficacy. There was no difference between the two groups in terms of ototoxicity, nephrotoxicity, duration of gentamicin treatment or time to fever defervescence. CONCLUSION: OD gentamicin is as efficacious as TDS gentamicin in the treatment of UTI in children, with no difference in ototoxicity and nephrotoxicity.

Adolescent↗
PubMed2003

Nasopharyngeal carcinoma in young patients.

Nasopharyngeal carcinoma (NPC) is rare in under 20-year-olds. Early diagnosis greatly improves survival. A retrospective review of 12 young NPC patients (seven males, five females, mean age 16 years) was performed to identify differing patient and tumour characteristics from adult NPC. Seventy-five per cent presented with neck lumps and 25% with headache. None had a family history of NPC or epistaxis. One patient had early stage NPC, and 11 had late stage NPC. Three late stage patients who received chemoradiotherapy had better clinical outcomes than six late stage patients receiving only radiotherapy. There were six deaths, five bony recurrences and one postnasal space recurrence. The 11 late stage patients' five-year actuarial survival was only 29%. Headache is an important symptom for young NPC. Late stage presentation and distant recurrences are also more common, supporting an increased role of chemotherapy.

Adolescent↗
PubMed2002

Novel substituted methylenedioxy lignan suppresses proliferation of cancer cells by inhibiting telomerase and activation of c-myc and caspases leading to apoptosis.

Conventional solvent fractionation and bioactivity based target assays were used to identify a new anti-cancer molecule from Phyllanthus urinaria, a herbal medicinal plant used in South India. At each step of the purification process the different fractions that were isolated were tested for specific anti-proliferative activity by assays measuring the inhibition of [(3)H]thymidine incorporation, and trypan blue drug exclusion. The ethyl acetate fraction that contained the bioactivity was further purified and resolved by HPLC on a preparative column. The purity of each of the fractions and their bioactivity were checked. Fraction 3 demonstrated a single spot on TLC and showed maximum anti-proliferative activity. This fraction was further purified and the structure was defined as 7'-hydroxy-3',4',5,9,9'-pentamethoxy-3,4-methylene dioxy lignan using NMR and mass spectrometry analysis. The pure compound and the crude ethyl acetate fraction which showed anti-proliferative activities were examined for ability to target specific markers of apoptosis like bcl2, c-myc and caspases and for effects on telomerase. Four specific cancer cell lines HEp2, EL-1 monocytes, HeLa and MCP7 were used in this study. The results indicate that 7'-hydroxy-3',4',5,9,9'-pentamethoxy-3,4-methylene dioxy lignan was capable of inhibiting telomerase activity and also could inhibit bcl2 and activate caspase 3 and caspase 8 whose significance in the induction of apoptosis is well known. We believe that this compound could serve as a valuable chemotherapeutic drug after further evaluations.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Extrusion of actin-positive strands from Hep-2 and Int 407 cells caused by outer membrane preparations of enteropathogenic Escherichia coil and specific attachment of wild type bacteria to the strands.

Enteropathogenic Escherichia coli (EPEC) causes persistent infantile diarrhoea. This nontoxigenic E. coli exhibits a complicated pathogenic mechanism in which its outer membrane proteins and type III secretory proteins damage intestinal epithelium and cause diarrhoea. In accordance with this, our previous study using HEp-2 cells demonstrated cytopathic effects caused by cell-free outer membrane preparations of EPEC. In this study, we report the extrusion of actin-positive strands from HEp-2 and Int 407 cells when treated with outer membrane preparations. An interesting observation of this work, perhaps relevant to the characteristic localized three-dimensional colony formation of EPEC, is the attachment of a wild type EPEC strain to these actin-positive strands.

Actin Cytoskeleton↗
PubMed2000

An unusual neck lump.

Oropharyngeal penetration and migration of ingested bodies into the neck is extremely rare. This is a case report of a 2-year-old boy who presented with a submental lump 1 day after swallowing a fish bone. The clinical, radiological, and intraoperative findings of the case are discussed.

Child, Preschool↗
PubMed2000

Epithelial cells release proinflammatory cytokines and undergo c-Myc-induced apoptosis on exposure to filarial parasitic sheath protein-Bcl2 mediates rescue by activating c-H-Ras.

Circulating filarial proteins elicit strong immunologic reactions in humans leading to the chronic manifestations in human lymphatic filariasis such as lymphatic occlusion, fibrosis, edema, and in some cases, tropical pulmonary eosinophilia. Our earlier studies, in vitro, conclusively prove that filarial parasitic sheath proteins induce apoptosis in HEp2 cells, an epithelial cell line, by a pathway inhibitable by bcl2. The present findings provide evidence that c-myc activation triggers apoptosis in HEp2 cells and that it is also responsible for the burst of abortive proliferation at 6 d of treatment of HEp2 bcl2 cells that overexpress bcl2, with filarial parasitic sheath protein, demonstrating the interplay between the two genes c-myc and bcl2, wherein bcl2 acts by restoring the prosurvival signal to c-myc and keeping its apoptotic tendency in check. This study also indicates that bcl2 upregulates c-H-ras, engaging ras to bring about the suppression of apoptosis through protein tyrosine kinase elevation, thus promoting the survival of the HEp2 bcl2 cells. In addition to the activation of these "signal switches," we also observe that these cells release cytokines like IL-6 and IL-8 through the upregulation of c-fos, when exposed to filarial parasitic sheath protein, reflecting on the immunomodulatory capacity of the epithelium to elicit a host immune response by setting up a chemotactic gradient, attracting inflammatory cells to the site of infection.

Animals↗
PubMed1998

Apoptosis induced by filarial parasitic sheath protein in HEp 2 cell lines blocked by ectopic expression of bcl 2.

Chronic filarial patients exhibit an occult manifestation, Tropical Pulmonary Eosinophilia, (TPE), caused by an exaggerated immune response to shed and circulating filarial antigens, leading to extensive lung damage. We have attempted to examine the disease in vitro using the human epithelial cell line, HEp2. Filarial sheath proteins induce apoptosis in HEp2 cells characterized by chromatin condensation, internucleosomal DNA cleavage, positive staining for TUNEL assay and shows a sub-G1 peak on FACS analysis. In order to understand subcellular events and to analyse the protective role of bcl2, we engineered HEp2 to overexpress Bcl2 protein. HEp2 bcl2 cells do not undergo apoptosis on exposure to filarial sheath protein, indicating that filarial protein-induced apoptosis in epithelial cells proceeds via a pathway, inhibitable by overexpression of bcl 2.

Animals↗
PubMed1998

A modified technique of tubeless anaesthesia for microlaryngoscopy and bronchoscopy in young children with stridor.

Sixty children including neonates and infants, with stridor undergoing investigations under general anaesthesia, were studied retrospectively. General anaesthesia was induced using an inhalational technique with halothane and was maintained with propofol infusion without the use of tracheal intubation. The ages ranged from three days to two years and five months. In most of the cases after propofol infusion, there was a slight drop in blood pressure without change in heart rate. This modified technique was found to be satisfactory in most of the cases.

Anesthesia, Inhalation↗
PubMed1998

Case report of Usher's syndrome in two sisters--first reported case in Singapore.

A 28-year-old Chinese woman presented with poor night vision since childhood. Ocular examination showed pigmentary retinopathy and systemic examination revealed sensorineural hearing loss. Family history showed a similar condition in her youngest sister. Ocular and systemic examination of her sister showed similar findings. This is presented as the first case report of Usher's syndrome in Singapore. A general discussion of Usher's syndrome is also presented.

Adult↗
PubMed1997

Necrosis of lung epithelial cells by filarial parasitic protein via an early induction of c-H-ras and TNF alpha expression.

The direct interaction of filarial proteins with lung epithelial cells was examined to determine the possible mechanism of inducing cell death, an event that is observed in patients with tropical pulmonary eosinophilia. Exposure of lung epithelial cells to filarial parasitic proteins, Brugia malayi (BmA), Setaria digitata (Sd), and recombinant filarial protein (pGT 7) in vitro for more than 2 days, causes the appearance of DNA fragments both in the cytoplasm and culture supernatants, while no fragmentation was observed in the untreated controls. The release of DNA fragments both in the cytoplasm and the culture supernatants simultaneously, indicates that cell death is induced by a necrotic event rather than apoptosis. Fluorescent-labelled studies also indicate the fragmentation of DNA increasing in a time-dependent manner. Normal cellular function is controlled through several oncogenes. The modulation of specific proto-oncogenes like myc, ras and TNF alpha during exposure to filarial parasitic proteins reveal elevated levels of expression of ras and TNF alpha as early as 2 hours, implicating their involvement prior to DNA fragmentation leading to pathogenesis.

Animals↗