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Biomedical subjects

C F Wong

Publications and source records attributed to C F Wong.

At least 19 recordsLinked to original sources
PubMed2005

Bronchiolitis obliterans organising pneumonia (BOOP) in a lung cancer patient after lobectomy.

A 79 year-old patient with lung cancer underwent a standard thoracotomy and lobectomy. Postoperatively, he developed low-grade fever and dyspnoea. Chest X-rays showed progressive lung infiltrates, which was subsequently diagnosed to be Bronchiolitis Obliterans Organizing Pneumonia (BOOP) by transbronchial lung biopsy. He responded well to corticosteroid therapy. The case report is followed by a brief discussion on BOOP in association with lung cancer and thoracotomy.

Aged↗
PubMed2001

Atomistic Brownian dynamics simulation of peptide phosphorylation.

We report the implementation of an all-atom Brownian dynamics simulation model of peptides using the constraint algorithm LINCS. The algorithm has been added as a part of UHBD. It uses adaptive time steps to achieve a balance between computational speed and stability. The algorithm was applied to study the effect of phosphorylation on the conformational preference of the peptide Gly-Ser-Ser-Ser. We find that the middle serine residue experiences considerable conformational change from the C(7eq) to the alpha(R) structure upon phosphorylation. NMR (3)J coupling constants were also computed from the Brownian trajectories using the Karplus equation. The calculated (3)J results agree reasonably well with experimental data for phosphorylated peptide but less so for doubly charged phosphorylated one.

Algorithms↗
PubMed2001

Computational analysis of PKA-balanol interactions.

Protein kinases are important targets for designing therapeutic drugs. This paper illustrates a computational approach to extend the usefulness of a single protein-inhibitor structure in aiding the design of protein kinase inhibitors. Using the complex structure of the catalytic subunit of PKA (cPKA) and balanol as a guide, we have analyzed and compared the distribution of amino acid types near the protein-ligand interface for nearly 400 kinases. This analysis has identified a number of sites that are more variable in amino acid types among the kinases analyzed, and these are useful sites to consider in designing specific protein kinase inhibitors. On the other hand, we have found kinases whose protein-ligand interfaces are similar to that of the cPKA-balanol complex and balanol can be a useful lead compound for developing effective inhibitors for these kinases. Generally, this approach can help us discover new drug targets for an existing class of compounds that have already been well characterized pharmacologically. The relative significance of the charge/polarity of residues at the protein-ligand interface has been quantified by carrying out computational sensitivity analysis in which the charge/polarity of an atom or functional group was turned off/on, and the resulting effects on binding affinity have been examined. The binding affinity was estimated by using an implicit-solvent model in which the electrostatic contributions were obtained by solving the Poisson equation and the hydrophobic effects were accounted for by using surface-area dependent terms. The same sensitivity analysis approach was applied to the ligand balanol to develop a pharmacophoric model for searching new drug leads from small-molecule libraries. To help evaluate the binding affinity of designed inhibitors before they are made, we have developed a semiempirical approach to improve the predictive reliability of the implicit-solvent binding model.

Azepines↗
PubMed2001

The structure of Sky1p reveals a novel mechanism for constitutive activity.

Sky1p is the only member of the SR protein kinase (SRPK) family in Saccharomyces cerevisiae. SRPKs are constitutively active kinases that display remarkable substrate specificity and have been implicated in RNA processing. Here we present the three-dimensional structure of a fully active truncated Sky1p. Analysis of the structure and structure-based functional studies reveal that the C-terminal tail, an unusual Glu residue located in the P+1 loop, and a unique mechanism for the positioning of helix alpha C act together to render Sky1p constitutively active. We have modeled a substrate peptide bound to Sky1p. The modeled complex combined with mutagenesis studies illustrate the molecular basis for substrate recognition by this kinase and suggest a mechanism by which SRPKs catalyze a sequential phosphorylation reaction of the consecutive RS dipeptide repeats characteristic of mammalian SRPK substrates.

Amino Acid Sequence↗
PubMed2001

Chronic necrotizing pulmonary aspergillosis. A report of 9 cases with analysis of clinical picture, risk factors and treatment for outcome correlation.

Nine patients with chronic necrotizing pulmonary aspergillosis (CNPA) were analyzed retrospectively. Eight cases had been treated with itraconazole. Four patients had received intravenous amphotericin B (AMB), three sequentially with itraconazole and one as monotherapy. Three patients died after 1, 2 and 24 weeks of therapy. Six responded to therapy and survived 3 to 58 months after treatment. Only the total number of risk factors was found to be statistically significant in relation to a fatal outcome. The mean number of risk factors was 5.33 for fatal cases compared to 2.83 for treatment responders. The presence of five or more risk factors and two individual risk factors, hypoalbuminemia less than 27 g/L and history of dual pulmonary mycobacterioses, were 100% predictive of mortality in our patients. The overall clinical picture of fatal CNPA cases resembles closely that of acute invasive pulmonary aspergillosis in severely immunocompromised subjects.

Aged↗
PubMed2000

Possible mechanism for drug retardation from glyceryl monostearate matrix system.

Lipophilicity was evaluated as a possible mechanism for drug retardation from a glyceryl monostearate matrix system. Lipophilicity of the glyceryl monostearate matrix system was studied using contact angle measurement of water droplets on the surface of compressed disks, extrudate ascension of water, and movement of water through a powder mixture packed in a high-performance liquid chromatographic (HPLC) column. Increase in glyceryl monostearate content resulted in an increase in water droplet contact angle, decrease in the rate of water ascending the extrudate, and increase in the pressure values as a function of flow rate of water moving through the powder mixture. These could be due to the increase in lipophilicity of the matrix, rendering the matrix less wettable. As a result, the rate of water penetration into the matrix decreased, and the drug release could be sustained.

Chemistry, Pharmaceutical↗
PubMed2000

Application of similarity factor in development of controlled-release diltiazem tablet.

Controlled-release grade hydroxypropylmethylcellulose (HPMC) or xanthan gum (XG) and microcrystalline cellulose (MCC) were employed to prepare controlled-release diltiazem hydrochloride tablets. The similarity factor f2 was used for dissolution profile comparison using Herbesser 90 SR as a reference product. Drug release could be sustained in a predictable manner by modifying the content of HPMC or XG. Moreover, the drug release profiles of tablets prepared using these matrix materials were not affected by pH and agitation rate. The f2 values showed that only one batch of tablets (of diltiazem HCl, HPMC or XG, and MCC in proportions of 3.0:3.0:4.0) was considered similar to that of the reference product, with values above 50. The unbiased similarity factor f2* values were not much different from the f2 values, ascribing to a small dissolution variance of the test and reference products. The amount of HPMC or XG incorporated to produce tablets with the desired dissolution profile could be determined from the curves of f2 versus polymer content. Hence, the f2 values can be applied as screening and optimization tools during development of controlled-release preparations.

Antihypertensive Agents↗
PubMed1999

An in-vitro method for buccal adhesion studies: importance of instrument variables.

A method using a texture analyzer equipment and chicken pouch as the biological tissue was investigated for measuring the bioadhesive properties of polymers under simulated buccal conditions. The method was evaluated using two polymers, namely Carbopol 974P and Methocel K4M while the instrument variables studied included the contact force, contact time and speed of withdrawal of the probe from the tissue. The parameters measured were the work of adhesion and peak detachment force. Longer contact time and faster probe speed not only gave better reproducibility of results, but also better sensitivities for both parameters measured. On the other hand, a certain level of contact force was found essential for achieving good bioadhesion, above which there was no further contribution to the bioadhesion process. When the method was applied to determine the bioadhesiveness of several polymers, the values obtained for the work of adhesion and peak detachment force were quite consistent in the ranking of the polymers. The Carbopols were found to have the highest values, followed by gelatin, sodium carboxymethyl celluloses and hydroxypropylmethyl celluloses. On the other hand, Alginic acid, Eudragit RLPO and RSPO, and Chitosan appeared to have low bioadhesive values.

Adhesives↗
PubMed1999

Formulation and evaluation of controlled release Eudragit buccal patches.

Controlled release buccal patches were fabricated using Eudragit NE40D and studied. Various bioadhesive polymers, namely hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose and Carbopol of different grades, were incorporated into the patches, to modify their bioadhesive properties as well as the rate of drug release, using metoprolol tartrate as the model drug. The in-vitro drug release was determined using the USP 23 dissolution test apparatus 5 with slight modification, while the bioadhesive properties were evaluated using texture analyzer equipment with chicken pouch as the model tissue. The incorporation of hydrophilic polymers was found to affect the drug release as well as enhance the bioadhesiveness. Although high viscosity polymers can enhance the bioadhesiveness of the patches, they also tend to cause non-homogeneous distribution of the polymers and drug, resulting in non-predictable drug-release rates. Of the various bioadhesive polymers studied, Cekol 700 appeared to be most satisfactory in terms of modifying the drug release and enhancement of the bioadhesive properties.

Acrylic Resins↗
PubMed1999

Improved recovery of Mycobacterium tuberculosis from pleural aspirates: bedside inoculation, heparinized containers and liquid culture media.

The effects of bedside inoculation, heparinized containers and liquid culture media on the recovery of Mycobacterium tuberculosis from pleural aspirates were evaluated in this study. Of 155 patients, 63 were diagnosed to have pleural effusion tuberculous in origin. The overall recovery of M. tuberculosis was 57.1%. Bedside inoculation of the specimens produced a significantly higher yield than laboratory inoculation using non-heparinized specimens. When the pleural aspirates were transported in heparinized containers, the recovery rate was comparable to that from bedside inoculation, but lower when non-heparinized containers were used. No significant difference was found in recovery rate between the two liquid media, but the rate was significantly higher with the use of liquid media than conventional solid media. Thus, bedside inoculation of pleural aspirates, use of heparinized containers for transport for delayed inoculation in the laboratory and use of liquid culture media are recommended.

Anticoagulants↗
PubMed1999

Report of eight cases of pulmonary actinomycosis and their treatment with imipenem-cilastatin.

Studies on the efficacy of antimicrobial agents against actinomycosis in vivo have been limited apart from those involving penicillin. A prospective ministudy on the efficacy of imipenem-cilastatin in the treatment of pulmonary actinomycosis was performed based on preliminary encouraging in vitro and in vivo data. Eight patients were diagnosed as having pulmonary actinomycosis using fibreoptic bronchoscopy (7) and percutaneous transthoracic needle biopsy (1) in the authors' unit between 1994 and 1996. Each patient received a 4-week course of imipenem-cilastatin that comprised 2 weeks of intravenously administered drug (500 mg at 8-hourly intervals) and 2 weeks of intramuscularly administered drug (500 mg at 12-hourly intervals). Seven patients showed a very good clinical and radiographic response as well as bronchoscopically-documented treatment success. Treatment failed in one patient. Amongst the former group, one patient was lost to follow-up, another relapsed 3 months after treatment cessation and the rest remained relapse-free when followed-up for 18-44 months (mean 30.2 months). Furthermore, all patients showed good clinical tolerance and no abnormal treatment-related laboratory findings. The favourable outcome for most patients in this mini-study suggest that a 4-week parenteral course of imipenem-cilastatin is an efficacious treatment for pulmonary actinomycosis. This antimicrobial regimen might be a promising alternative to the time-honoured long-course treatment with intravenous and oral penicillin.

Actinomycosis↗
PubMed1999

Fibreoptic bronchoscopy in the diagnosis of lung cancer.

A total of 562 patients with lung cancer was evaluated by fibreoptic bronchoscopy (FOB) by three bronchoscopic diagnostic procedures: biopsy, bronchial brushing and bronchial washing. Endoscopically visible tumours (EV) were detected in 264, while 257 had endoscopically nonvisible tumours > or = 2 cm in diameter and FOB was done without fluoroscopy because of limited availability (ENV). Forty-one had small (< 2 cm), endoscopically nonvisible tumours with FOB performed under uniplanar fluoroscopy (ENV + F). The overall diagnostic yield rates of FOB were 98.1%, 61.5% and 58.5% for the EV, ENV and ENV + F cases, respectively. Reviewing the differential yield rates of the three diagnostic techniques and comparing them with the results of previous studies led to the following conclusions. (1) Combinations of biopsy with brushing and biopsy with washing can diagnose more than 95% of all fibreoptic bronchoscopy positive cases with endoscopically visible tumours. Performing either of these combinations may be more cost-effective than doing all three techniques routinely. (2) For cases with endoscopically nonvisible tumours, performance of all three diagnostic techniques is recommended, especially when fibreoptic bronchoscopy is performed without fluoroscopic guidance, as washing and brushing seem to compensate for a lower yield of the biopsy. (3) For tumours < 2 cm in diameter, knowledge on the diagnostic efficacy of fibreoptic bronchoscopy was limited owing to the small size of previous studies. The yield of 58.5% for fibreoptic bronchoscopy in these patients with performance of all three diagnostic procedures was comparatively high. It could be further increased to 75.6% if supplemented by percutaneous needle biopsy when fibreoptic bronchoscopy turned out to be nondiagnostic. If available, the use of transbronchial needle aspiration may also increase the overall diagnostic yield of fibreoptic bronchoscopy in these cases.

Biopsy↗
PubMed1999

Serum pharmacokinetics of antimycobacterial drugs in patients with multidrug-resistant tuberculosis during therapy.

Serum samples of 13 patients with multidrug-resistant tuberculosis were taken 0, 1, 2, 4, 8 h after administration of antimycobacterial drugs for assay of levels in order to gain further insight into their basic pharmacokinetics. The drugs assessed were amikacin, kanamycin, ofloxacin, levofloxacin, para-aminosalicylic acid, prothionamide, cycloserine, pyrazinamide and ethambutol. Techniques used for assay were reversephase high-performance liquid chromatography, gas liquid chromatography and fluorescent polarization immunoassay. The results from 12 patients were evaluated. These provided new pharmacokinetic data on high-dose levofloxacin, cycloserine and prothionamide given once daily, and could be useful in guiding the scheduling of drugs. The data obtained might also lead to insights into the development of therapeutic drug monitoring in multidrug-resistant tuberculosis.

Adult↗
PubMed1998

Simple high-performance liquid chromatographic method for the determination of ranitidine in human plasma.

A simple high-performance liquid chromatographic method was developed for the determination of ranitidine in human plasma. Prior to analysis, ranitidine and the internal standard (metoprolol) were extracted from alkalinized plasma samples using dichloromethane. The mobile phase was 0.05 M potassium dihydrogenphosphate-acetonitrile (88:12, v/v) adjusted to pH 6.5. Analysis was run at a flow-rate of 1.3 ml/min and at a detection wavelength of 229 nm. The method is sensitive with a detection limit of 1 ng/ml at a signal-to-noise ratio of 3:1, while the quantification limit was set at 15 ng/ml. The calibration curve was linear over a concentration range of 15-2000 ng/ml. Mean recovery value of the extraction procedure was about 90%, while the within-day and between-day coefficients of variation and percent error values of the assay method were all less than 15%.

Adult↗
PubMed1998

Simulating energy flow in biomolecules: application to tuna cytochrome c.

By constructing a continuity equation of energy flow, one can utilize results from a molecular dynamics simulation to calculate the energy flux or flow in different parts of a biomolecule. Such calculations can yield useful insights into the pathways of energy flow in biomolecules. The method was first tested on a small system of a cluster of 13 argon atoms and then applied to the study of the pathways of energy flow after a tuna ferrocytochrome c molecule was oxidized. Initially, energy propagated faster along the direction perpendicular to the heme plane. This was due to an efficient through-bond mechanism, because the heme iron in cytochrome c was covalently bonded to a cysteine and a histidine. For the oxidation of cytochrome c, electrostatic interactions also facilitated a long-range through-space mechanism of energy flow. As a result, polar or charged groups that were further away from the oxidation site could receive energy earlier than nonpolar groups closer to the site. Another bridging mechanism facilitating efficient long-range responses to cytochrome c oxidation involved the coupling of far-off atoms with atoms that were nearer to, and interacted directly with, the oxidation site. The different characteristics of these energy transfer mechanisms defied a simple correlation between the time that the excess energy of the oxidation site first dissipated to an atom and the distance of the atom from the oxidation site. For tuna cytochrome c, all of the atoms of the protein had sensed the effects of the oxidation within approximately 40 fs. For the length scale of energy transfer considered in this study, the speed of the energy propagation in the protein was on the order of 10(5) m/s.

Animals↗
PubMed1998

Rapid diagnosis of smear-negative pulmonary tuberculosis via fibreoptic bronchoscopy: utility of polymerase chain reaction in bronchial aspirates as an adjunct to transbronchial biopsies.

Fibreoptic bronchoscopy was performed on 190 patients with chest radiographic lesions and negative sputum smears for acid-fast bacilli. Aside from obtaining transbronchial biopsies for histological examination, bronchial aspirate specimens were also tested for Mycobacterium tuberculosis complex DNA by a conventional polymerase chain reaction (PCR) technique. Of 177 transbronchial biopsies performed, a diagnosis was found in 64 cases [43 cases of tuberculosis (TB), 17 cases of lung carcinoma and four cases of other infective/inflammatory diseases] giving a diagnostic yield of 36.2%. PCR was positive in 105 of 108 finally diagnosed cases of TB and 22 of 82 non-TB cases. The sensitivity, specificity, positive predictive value and negative predictive value of PCR when applied to bronchial aspirate specimens for diagnosing smear-negative pulmonary TB were 97.2%, 73.2%, 82.7% and 95.2% respectively. Therefore, detection of M. tuberculosis complex DNA in bronchial aspirates by PCR might have an adjunctive place to transbronchial biopsies in the rapid diagnosis of smear-negative pulmonary tuberculosis.

Adolescent↗