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Biomedical subjects

S T Lim

Publications and source records attributed to S T Lim.

At least 19 recordsLinked to original sources
PubMed2006

Association analysis of endothelial nitric oxide synthase gene polymorphism with primary hypertension in a Singapore population.

Vascular endothelial cells produce nitric oxide (NO), which contributes to the regulation of blood pressure and regional blood flow. Endothelial nitric oxide synthase (eNOS) gene polymorphisms are associated with coronary artery disease, but their linkage with primary hypertension is controversial. A total of 103 individuals with primary hypertension and 104 normotensive control subjects were studied in Singapore. The specific genotypes for G894T missense variant in exon 7, variable number tandem repeats (VNTR) in intron 4 (eNOS 4A/B/C) and T-786C in the promoter were isolated using allele-specific gene amplification and restriction fragment length polymorphism to examine the association of genotype and allelic frequency in both groups. Logistic regression analysis was also used to detect the association between genotypes and hypertension. Five genotypes of intron 4 VNTR (AA, AB, BB, AC and BC) were observed. Intron 4 B/B genotype was significantly associated with the hypertension group (P = 0.035), but disequilibrium of G894T and T-786C was absent between the two groups (P = 0.419 and P = 0.227), respectively. The overall distribution of allelic frequency differed significantly between the two groups, with four-repeat allele (4A) of intron 4 more frequent in the normotensive group than the hypertensive group (P = 0.019). Logistic regression analysis showed that intron 4 B/B genotype was significantly associated with systolic blood pressure of individuals with body mass index greater than 25 kg/m2 (P = 0.04). In conclusion, the eNOS 4 B/B genotype is a genetic susceptibility factor for primary hypertension in a Singapore population.

Blood Pressure↗
PubMed2005

Inter- and intralaboratory variation of in vitro diffusion cell measurements: an international multicenter study using quasi-standardized methods and materials.

In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. "Standardized" calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 microg cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 microg cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intralaboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required.

Clinical Laboratory Techniques↗
PubMed2005

Can patients with early-stage diffuse large B-cell lymphoma be treated without bone marrow biopsy?

BACKGROUND: Data on the incidence of bone marrow (BM) involvement in early-stage diffuse large B-cell lymphoma (DLBCL) are lacking. Although BM biopsy is a safe procedure, it is often poorly tolerated. This analysis aims to assess the incidence of BM involvement and to identify parameters predicting BM involvement in early-stage DLBCL. PATIENTS AND METHODS: One hundred and ninety-two patients with radiological stages 1 and 2 disease were analysed. The data collected were age, sex, presence of B symptoms, white blood cell (WBC) count, platelet count, haemoglobin (Hb), serum lactate dehydrogenase level, serum beta(2)-microglobulin level, presence of extranodal disease, and the presence of bulky disease (defined as >7 cm). RESULTS: Overall incidence of BM involvement was 3.6%. Hb < 10 g/dl (P=0.02), WBC count < 4 x 10(9)/l (P=0.007) and bulky disease (P=0.06) were found to be predictive of BM involvement. Among the 120 patients without any of these three factors, only one patient had BM involvement (0.83%; 95% confidence interval 0.02% to 4.6%). The absence of all three factors gave a negative predictive value of 99.2%. Overall 3-year survival for patients without all three risk factors was 80%. CONCLUSIONS: BM biopsy may be safely omitted in selected patients with early-stage DLBCL.

Bone Marrow Examination↗
PubMed2004

Posterior mediastinal paraganglioma with bilateral adrenal pheochromocytoma.

Paraganglioma and adrenal pheochromocytoma are tumors of common origin arising from chromaffin cells. However, it is extremely rare to find mediastinal paraganglioma simultaneously with bilateral adrenal pheochromocytoma. We report a 53-year-old man who was diagnosed with posterior mediastinal paraganglioma and bilateral adrenal pheochromocytoma and who underwent successful excision of the posterior mediastinal mass and bilateral total adrenalectomy.

Adrenal Gland Neoplasms↗
PubMed2003

CPT-11 and cisplatin in the treatment of advanced gastric cancer in Asians.

There is no standard chemotherapy for advanced gastric cancer. A combination of CPT-11 and cisplatin was evaluated for response and toxicity in Asians. 38 patients with histologically proven stage IV gastric/gastroesophageal junction adenocarcinoma were treated with CPT-11 50 mg/m2 and cisplatin 30 mg/m2 weekly for 3 weeks. Each cycle was repeated every 28 days. The median number of cycles was 1.66 (range 0.33-4.33). Dose delay was needed in 11 (29%) patients and dose reductions in 19 (50%) patients. The overall response rate was 42%. There was no complete response. Grade 3 and 4 hematological toxicity was 26%. Grade 3 or 4 diarrhea was not common. Median time to progression for all patients was 15 weeks. Median duration of survival of all patients was 42 weeks. Patients with better performance status and no prior chemotherapy did better. CPT-11 and cisplatin is a useful regimen with significant but manageable toxicity that can be administered without a central venous catheter.

Adenocarcinoma↗
PubMed2002

Turbulent drag reduction and degradation of DNA.

Turbulent drag reduction induced by lambda-DNA is studied. The double-stranded DNA is found to be a good drag reducer when compared with the other normal linear polymers. However, this drag reducing power disappears when the DNA denatures to form two single-strand molecules. Mechanical degradation of DNA is also different from that of the normal linear-chain polymers: DNA is always cut in half by the turbulence. Our results suggest that the mechanism for turbulent degradation of DNA is different from that of the normal flexible long-chain polymers.

Bacteriophage lambda↗
PubMed2002

Analysis of alkali-soluble glucan produced by Saccharomyces cerevisiae wild-type and mutants.

The alkali-soluble glucan of the yeast cell wall contains beta-(1,3)- and (1,6)-D-linkages and systemically enhances the immune system. To isolate Saccharomyces cerevisiae mutants producing glucan with a high degree of beta-(1,6)-D-glycosidic bonds, a wild-type strain was mutagenized with ultraviolet light. The mutants were then selected by treatment with 1.0 mg laminarinase, endo-beta-(1,3)-D-glucanase/ml. The alkali-soluble glucan was extracted by modified alkalysis followed by the Cetavlon method and concanavalin-A chromatography. The prepared alkali-soluble glucans from the wild-type and the mutants were compared with respect to yield and polymer structure using gas chromatography, 13C-NMR spectrometry, high performance liquid, and multi-angle laser light scattering and refractive index detectors. The results indicated that the S. cerevisiae mutants had ten-fold more alkali-soluble glucan than the wild-type. Structural analysis revealed that the alkali-soluble glucan from the mutants also had a higher degree of beta-(1,6)-D-linkage than that from the wild-type.

Alkalies↗
PubMed2002

In vivo evaluation of novel hyaluronan/chitosan microparticulate delivery systems for the nasal delivery of gentamicin in rabbits.

Biodegradable microparticles containing gentamicin were prepared using chitosan hydroglutamate (CH), hyaluronic acid (HA) and a combination of both polymers by a solvent evaporation method. These formulations were administered nasally via an insufflator. Gentamicin was also administered nasally into rabbits as a solution and powder (a physical mixture of gentamicin and lactose), intravenously (IV) and intramuscularly (IM). The resultant serum levels of gentamicin were determined by Fluorescence Polarisation Immunoassay (FPIA). The bioavailability of gentamicin was poor when administered as a nasal solution (1.1%) and dry powder (2.1%) when compared with IV. However, the microparticulate systems composed of CH and HA/CH considerably enhanced the bioavailability of gentamicin (31.4 and 42.9%, respectively,) with HA microparticles inducing a less significant enhancement (23.3%). Previous in vitro dissolution and frog palate studies indicated that these microparticulate formulations were all mucoadhesive and demonstrated prolonged drug release. Such findings were translated into an increase in the bioavailability of gentamicin when compared with a simple nasal solution in vivo. When HA and CH were combined in the HA/CH formulation, the polymers appeared to improve the absorption of incorporated gentamicin synergistically in comparison to the individual polymers, suggesting a promising nasal delivery system.

Adjuvants, Pharmaceutic↗
PubMed2002

Rheumatic heart diseases in pregnancy.

Acute rheumatic fever and rheumatic valvular disease remain prevalent in many parts of the world, and are probably the most common cause of heart disease in pregnancy. Mitral stenosis is the most frequently encountered rheumatic valvular lesion. A variety of pregnancy-associated cardiovascular changes often exacerbate the signs and symptoms of valvular lesions. Pregnancy should not be allowed to proceed, if possible, in patients with uncorrected severe valvular lesions or mechanical heart valves requiring anticoagulation, as maternal and fetal morbidity and mortality are high. For those with milder disease, pregnancy is best undertaken after the valvular lesion has been rectified or stabilised. Recent advances in the management of valvular disease include the use of beta-blockers for patients with mitral stenosis, vasodilators in those with aortic and mitral regurgitation, and percutaneous balloon valvuloplasty for mitral and aortic stenosis. Application of these therapies in the pregnant patient is as yet unclear, and management decision needs to be individualized, weighing the risk and benefit to ensure maternal survival and to promote fetal well-being.

Acute Disease↗
PubMed2001

In vivo and in vitro characterization of novel microparticulates based on hyaluronan and chitosan hydroglutamate.

This study examined the application of previously characterized microparticles composed of hyaluronan (HA) and chitosan hydroglutamate (CH) as well as novel microparticles consisting of both polymers (HA/CH) to improve the nasal delivery of a model drug. The rabbit bioavailabilities of gentamicin incorporated in HA, CH, and HA/CH microparticles were increased 23-, 31-, and 42-fold, respectively, compared with the control intranasal solution of gentamicin, indicating that all test microparticles were retained for longer periods on the nasal mucosa of the rabbits as supported by previous in vitro dissolution as well as frog palate mucoadhesion studies, thereby improving drug absorption. The higher bioavailabilities of CH-based formulations (CH and HA/CH) suggest the penetration-enhancing effects of CH may also be partially responsible for the improvement. A model was developed, based on a glass impinger device, to deliver dry powder formulations reproducibly onto the surface of cultured cell monolayers. In vitro permeability and fluorescence microscopy studies on the tight junctions of the 16HBE14o- cell lines further confirmed the ability of CH-based formulations to enhance penetration. Furthermore, the in vitro absorption profile from cell culture studies was consistent with those determined from in vivo studies. The complementary effect from the mucoadhesive nature of HA coupled with the penetration-enhancing effects of CH makes the novel HA/CH formulation a promising nasal delivery system.

Administration, Intranasal↗
PubMed2001

Dynamic localization and clustering of dendritic Kv2.1 voltage-dependent potassium channels in developing hippocampal neurons.

Dendritic excitability is modulated by the highly variable spatial and temporal expression pattern of voltage-dependent potassium channels. Somatodendritic Kv2.1 channels contribute a major component of delayed rectifier potassium current in cultured hippocampal neurons, where Kv2.1 is localized to large clusters on the soma and proximal dendrites. Here we found that dramatic differences exist in the clustering of endogenous Kv2.1 in cultured rat hippocampal GABAergic interneurons and glutamatergic pyramidal neurons. Studies on neurons developing in culture revealed that while a similar sequence of Kv2.1 localization and clustering occurred in both cell types, the process was temporally delayed in pyramidal cells. Localization and clustering of recombinant green fluorescent protein-tagged Kv2.1 occurred by the same sequence of events, and imaging of GFP-Kv2.1 clustering in living neurons revealed dynamic fusion events that underlie cluster formation. Overexpression of GFP-Kv2.1 accelerated the clustering program in pyramidal neurons such that the observed differences in Kv2.1 clustering in pyramidal neurons and interneurons were eliminated. Confocal imaging showed a preferential association of Kv2.1 with the basal membrane in cultured neurons, and electrophysiological recordings from neurons cultured on transistors revealed that Kv2.1 contributed the bulk of a previously described adherens junction delayed rectifier potassium conductance. Finally, Kv2.1 clusters were found spatially associated with ryanodine receptor intracellular Ca(2+) ([Ca(2+)](i)) release channels. These findings reveal a stepwise assembly of Kv2.1 potassium channels into membrane clusters during development, and an association of these clusters with Ca(2+) signaling apparatus. Together these data suggest that the restricted localization of Kv2.1 may play an important role in the previously observed contribution of this potassium channel in regulating dendritic [Ca(2+)](i) transients.

Animals↗
PubMed2001

Monthly variation in human semen quality in male partners of infertile women in the tropics.

The aim of the study was to determine whether there were significant 'seasonal' variations in the rhythm of sperm parameters (i.e. semen volume and sperm density) of men who reside in the tropics. A total of 7656 semen analysis results from the department of obstetrics and gynaecology of a tertiary general hospital was analysed. These samples were obtained as part of an initial screening for male partners of couples with problems trying to conceive who were attending a fertility clinic from 1991 to 1995. The subjects' mean semen volume and sperm density of 2.9 ml and 26.9x10(6)/ml respectively were within the World Health Organization reference values. There were no significant month-to-month variations in the adjusted (for age of subject, year of test and technologist who performed the analysis by analysis of co-variance, ANCOVA) mean semen volume and sperm density over the 5 year period. Variations in semen volume and density observed in the temperate climates are not seen in this study, which was conducted in subjects staying in the tropics. This observation may be related to relative constant temperature and hours of light exposure among men who reside in the tropics. As this study is, so far, published data from only one country, Singapore, it may not truly reflect the actual situation for individuals who are residing in the tropics.

Adult↗