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Biomedical subjects

M F Chan

Publications and source records attributed to M F Chan.

At least 19 recordsLinked to original sources
PubMed2003

Attitudes of Hong Kong Chinese to traditional Chinese medicine and Western medicine: survey and cluster analysis.

OBJECTIVES: To determine whether within a cohort of Hong Kong out-patients definable subtypes exist based on their attitudes to traditional Chinese medicine and Western medicine. DESIGN: Data were collected using a structured questionnaire. SETTING: The sample of 503 subjects was recruited at two local outpatient clinics in Hong Kong. MAIN OUTCOME MEASURES: The study employs demographic variables, illness status, the Chinese-Western Medical Belief Scale, trust of physicians and subjects' preferences on consultation fees, attitude of health care professional, efficacy of service and waiting time during consultation. RESULTS: A cluster analysis yielded three clusters based on their attitudes towards traditional Chinese and Western medicine. One cluster, 24% of the sample, is noted for being older, poorer, more likely to be female and to have chronic conditions; they are sceptical of western physicians. The second cluster (63% of the sample) is younger and have considerably more belief in Western than traditional Chinese medicine. The third group (14%) is intermediate in age and is noted for a marked faith in both forms of medicine. CONCLUSIONS: A clear profile of these attitudes of Hong Kong Chinese may benefit health care professionals in making appropriate patient-doctor relationships and planning patient care.

Adolescent↗
PubMed2002

A parameter optimization algorithm for intensity-modulated radiotherapy prostate treatment planning.

An iterative algorithm has been developed to analytically determine patient specific input parameters for intensity-modulated radiotherapy prostate treatment planning. The algorithm starts with a generic set of inverse planning parameters that include dose and volume constraints for the target and surrounding critical structures. The overlap region between the target volume and the rectum is used to determine the optimized target volume coverage goal. Sequential iterations are performed to vary the numerous parameters individually or in sets while other parameters remain fixed. A coarse grid search is first used to avoid convergence on a local maximum. Linear interpolation is then used to define a region for a fine grid search. Selected parameters are also tested for possible improvements in target coverage. In several representative test cases investigated the coverage of the planning target volume improved with the use of the algorithm while still meeting the clinical acceptability criteria for critical structures. The algorithm avoids time-consuming random trial and error variations that are often associated with difficult cases and also eliminates lengthy user learning curves. The methodology described in this paper can be applied to any treatment planning system that requires the user to select the input optimization parameters.

Algorithms↗
PubMed2001

Delivery of intensity-modulated radiation therapy with a conventional multileaf collimator: comparison of dynamic and segmental methods.

Intensity-modulated radiation therapy (IMRT) can be delivered with a conventional multileaf collimator (MLC), either in dynamic mode (DMLC) or in segmental mode (SMLC, also known as "step-and-shoot"). The advantage of DMLC is its ability to deliver the desired intensity profile produced by inverse planning with a high degree of fidelity. The SMLC method, on the other hand, resembles treatment with multiple static fields, and can be more easily verified. However, the use of SMLC requires that the desired profile be approximated by discrete levels of intensity, which may lead to degradation in the delivered dose distribution. Clearly, the results of SMLC delivery depend on the number of levels and the spatial resolution of the intensity distribution. In this work, we compare the DMLC method and the SMLC method employing different numbers of levels and different spatial resolutions. Three disease sites were studied: prostate, nasopharynx, and breast, with three cases for each. In general, a 5- to 10-level SMLC plan produced results comparable to that from a DMLC plan. The target coverage is improved by increasing the number of levels while critical organs are better protected with finer spatial resolutions. The beam-on-time (MUs) requirement for SMLC was approximately 20% less than DMLC, but the delivery time (in minutes) was about twice as long. Thus, the choice depends on many factors including machine capability, quality assurance, target coverage, critical organ protection, beam-on-time, delivery time, and other clinical considerations.

Breast Neoplasms↗
PubMed2001

The treatment of large extraskeletal chondrosarcoma of the leg: comparison of IMRT and conformal radiotherapy techniques.

Extraskeletal chondrosarcoma of the leg is a rare, malignant neoplasm with very few cases having been reported in the literature. In this study we investigate the possibility of using intensity modulated radiotherapy (IMRT) for this type of disease and demonstrate its advantages over conventional three-dimensional (3D) conformal treatment. A case was presented of a patient with extraskeletal chondrosarcoma of the lateral compartment of the leg in which the target volume was 50 cm in length and twisted around the surrounding bones. Both the 3D conformal plan and IMRT plan were designed using the Memorial Sloan-Kettering Cancer Center planning system. The IMRT plan produced a superior dose distribution to the patient as compared to the 3D conformal plan both in terms of dose conformity and homogeneity in the target volumes, and reduction of the maximum dose to the bone. The planning time of the IMRT plan was about 3-5 times shorter than that of the 3D conformal plan. It was demonstrated that the IMRT technique can be used not just for small tumors, but also for large and spiral-shaped tumors close to critical organs. The IMRT method requires less planning time, and provides better target coverage with more sparing of critical structures. When planning patients with multiple target volumes receiving different prescribed doses, the IMRT technique can more easily meet this requirement.

Adult↗
PubMed2001

The measurement of three dimensional dose distribution of a ruthenium-106 ophthalmological applicator using magnetic resonance imaging of BANG polymer gels.

The BANG (MGS Research Inc., Guilford, CT) polymer gel has been used as a dosimeter to determine the three-dimensional (3D) dose distribution of a ruthenium-106 (Ru-106) ophthalmologic applicator. An eye phantom made of the BANG gel was irradiated with the Ru-106 source for up to 1 h. The phantom and a set of calibration vials were scanned simultaneously in a GE 1.5 T MR imager using the Hahn spin-echo pulse sequence with a TR of 2000 ms and two TEs of 20 ms and 100 ms. The T(2) values were evaluated on a pixel-by-pixel basis using custom-built software on a DEC alpha workstation and converted to dose using calibration data. Depth doses and isodose lines of the Ru-106 eye-plaque were generated. It is concluded that the BANG gel dosimetry offers the potential for measuring the 3D dose distributions of an ophthalmologic applicator, with high spatial resolution and relatively good accuracy.

Brachytherapy↗
PubMed2001

Reduced rates of gene loss, gene silencing, and gene mutation in Dnmt1-deficient embryonic stem cells.

Tumor suppressor gene inactivation is a crucial event in oncogenesis. Gene inactivation mechanisms include events resulting in loss of heterozygosity (LOH), gene mutation, and transcriptional silencing. The contribution of each of these different pathways varies among tumor suppressor genes and by cancer type. The factors that influence the relative utilization of gene inactivation pathways are poorly understood. In this study, we describe a detailed quantitative analysis of the three major gene inactivation mechanisms for a model gene at two different genomic integration sites in mouse embryonic stem (ES) cells. In addition, we targeted the major DNA methyltransferase gene, Dnmt1, to investigate the relative contribution of DNA methylation to these various competing gene inactivation pathways. Our data show that gene loss is the predominant mode of inactivation of a herpes simplex virus thymidine kinase neomycin phosphotransferase reporter gene (HSV-TKNeo) at the two integration sites tested and that this event is significantly reduced in Dnmt1-deficient cells. Gene silencing by promoter methylation requires Dnmt1, suggesting that the expression of Dnmt3a and Dnmt3b alone in ES cells is insufficient to achieve effective gene silencing. We used a novel assay to show that missense mutation rates are also substantially reduced in Dnmt1-deficient cells. This is the first direct demonstration that DNA methylation affects point mutation rates in mammalian cells. Surprisingly, the fraction of CpG transition mutations was not reduced in Dnmt1-deficient cells. Finally, we show that methyl group-deficient growth conditions do not cause an increase in missense mutation rates in Dnmt1-proficient cells, as predicted by methyltransferase-mediated mutagenesis models. We conclude that Dnmt1 deficiency and the accompanying genomic DNA hypomethylation result in a reduction of three major pathways of gene inactivation in our model system.

DNA (Cytosine-5-)-Methyltransferase 1↗
PubMed2000

Replacement of the carboxylic acid group of prostaglandin f(2alpha) with a hydroxyl or methoxy substituent provides biologically unique compounds.

Replacement of the carboxylic acid group of PGF(2alpha) with the non-acidic substituents hydroxyl (-OH) or methoxy (-OCH(3)) resulted in an unexpected activity profile. Although PGF(2alpha) 1-OH and PGF(2alpha) 1-OCH(3) exhibited potent contractile effects similar to 17-phenyl PGF(2alpha) in the cat lung parenchymal preparation, they were approximately 1000 times less potent than 17-phenyl PGF(2alpha) in stimulating recombinant feline and human FP receptors. In human dermal fibroblasts and Swiss 3T3 cells PGF(2alpha) 1-OH and PGF(2alpha) 1-OCH(3) produced no Ca(2+) signal until a 1 microM concentration was exceeded. Pretreatment of Swiss 3T3 cells with either 1 microM PGF(2alpha) 1-OH or PGF(2alpha) 1-OCH(3) did not attenuate Ca(2+) signal responses produced by PGF(2alpha) or fluprostenol. In the rat uterus, PGF(2alpha) 1-OH was about two orders of magnitude less potent than 17-phenyl PGF(2alpha) whereas PGF(2alpha) 1-OCH(3) produced only a minimal effect. Radioligand binding studies on cat lung parenchymal plasma membrane preparations suggested that the cat lung parenchyma does not contain a homogeneous population of receptors that equally respond to PGF(2alpha)1-OH, PGF(2alpha)1-OCH(3), and classical FP receptor agonists. Studies on smooth muscle preparations and cells containing DP, EP(1), EP(2), EP(3), EP(4), IP, and TP receptors indicated that the activity of PGF(2alpha) 1-OH and PGF(2alpha) 1-OCH(3) could not be ascribed to interaction with these receptors. The potent effects of PGF(2alpha) 1-OH and PGF(2alpha) 1-OCH(3) on the cat lung parenchyma are difficult to describe in terms of interaction with the FP or any other known prostanoid receptor.

3T3 Cells↗
PubMed1999

Psychologic response of the edentulous patient after primary surgery for oral cancer: A cross-sectional study.

STATEMENT OF PROBLEM: Edentulous patients can have difficulty in tolerating dentures and this may lead to psychologic disturbance. The problem is potentially more severe for edentulous patients after primary surgery for oral cancer, where treatment can include composite resection and reconstruction, followed by adjuvant radiotherapy. PURPOSE: This study investigated the psychologic response and oral satisfaction of edentulous patients treated by surgery for oral squamous cell carcinoma, and to make a comparison to edentulous noncancer counterparts. METHODS AND MATERIAL: The cross-sectional study included patients who were alive and disease-free 2 to 3 years after primary surgery. Seventy patients underwent surgery at the Regional Maxillofacial Unit, Liverpool, in 1993 and 1994. Twenty-eight patients were disease-free; 26 completed questionnaires that included a general health questionnaire (GHQ), a body satisfaction scale, a self-esteem scale, an oral symptom checklist, and a denture satisfaction questionnaire. Comparison was made with 98 noncancer edentulous patients from the same unit. RESULTS: There were similarities in psychologic and oral satisfaction scores between the noncancer and cancer edentulous patients. Cancer patients reported lower self-esteem (P <.02). Cancer patients who were not rehabilitated with either conventional or implant-retained prostheses had significant psychologic morbidity as measured by the GHQ, self-esteem, and body satisfaction scales. Cancer patients with implant-retained overdentures reported greater satisfaction with their dentures compared with their counterparts who wore conventional dentures (P <.05). CONCLUSION: Edentulous cancer patients who do not achieve oral rehabilitation after surgery for oral cancer exhibited significant psychologic morbidity. Patients with implant-retained overdentures exhibited a tendency to adopt the same psychologic response with improved denture satisfaction as edentulous patients with conventional dentures, despite the former having more extensive disease that would otherwise make the provision of dentures much more difficult if implants were not used.

Aged↗
PubMed1999

Botulinum toxin injections for achalasia symptoms can approximate the short term efficacy of a single pneumatic dilation: a survival analysis approach.

OBJECTIVE: Botulinum toxin injection can induce a temporary symptomatic remission in some patients with achalasia, but the comparative utility of the approach is not fully known. This study used survival analysis methods to better understand the ability of single or repeated botulinum toxin injections to postpone the need for other treatments. METHODS: The response to botulinum toxin in 42 patients with idiopathic achalasia who had not received prior treatment was compared with the outcome in 26 consecutive patients who underwent initial treatment with pneumatic dilation. Survival analysis methods were employed using time to retreatment as the principal outcome measure. RESULTS: Retreatment (any type) was required in 50% of subjects at 265 days (0.73 yr) after the first botulinum toxin injection. In contrast, retreatment after initial pneumatic dilation was required in <40% of patients after 2 and 5 yr of follow-up. The curves became significantly separated (p < 0.05) within 1 yr after initial treatment. Of those treated solely with botulinum toxin injections, repeated as needed, only 46% required pneumatic dilation or surgery by 2 yr. Survival analysis curves for repeated injections and initial pneumatic dilation did not differ statistically at 1 or 2 yr (p = 0.5 and p = 0.4, respectively). Correlational analyses indicated that, of the clinical parameters tested, only the degree of dysphagia for liquids was useful in selecting the better responders to botulinum toxin injections, with lesser symptoms predicting longer time to retreatment. CONCLUSIONS: Botulinum toxin injections, repeated as needed, can approximate the benefits of a single pneumatic dilation for < or = 2 yr from the standpoint of usual factors that drive further management.

Botulinum Toxins, Type A↗
PubMed1998

The discovery and structure-activity relationships of nonpeptide, low molecular weight antagonists selective for the endothelin ET(B) receptor.

The systematic modification of the ETA selective N-(5-isoxazolyl)benzene-sulfonamide endothelin antagonists to give ETB selective antagonists is reported. The reversal in selectivity was brought about by substitution of the 4-position with aryl and substituted aryl groups. Of all the aromatic substituents studied, the para-tolyl group gave rise to the most active and selective ETB antagonist. Larger substituents caused a decrease in both ETB activity and selectivity. A similar trend was observed by substitution at the 5-position of the N-(5-isoxazolyl)-2-thiophenesulfonamide ETA receptor antagonists. The para-tolyl group was again found to be optimal for the ETB activity and selectivity. The structural features that were found to be favorable for binding to the ETB receptor, that is, the presence of a linear, conjugated pi-system of definite shape and size, have been successfully incorporated into the design of ETB selective polycyclic aromatic sulfonamides antagonists.

Animals↗
PubMed1998

The swing-lock removable partial denture in clinical practice.

The authors of this article consider that the swing-lock partial denture has a useful place in contemporary clinical dental practice and offers many advantages compared with conventional removable partial dentures in terms of retention and stability, especially in the extremely compromised dentitions. Here they describe the concept of the swing-lock removable partial denture, together with the indications, contraindications, technical and clinical considerations.

Dental Abutments↗
PubMed1997

Structure-activity relationships of N2-aryl-3-(isoxazolylsulfamoyl)-2-thiophenecarboxamides as selective endothelin receptor-A antagonists.

We report here that N2-aryl-3-(isoxazolylsulfamoyl)-2-thiophenecarboxamides are potent and selective small molecule ETA receptor antagonists. The aryl group was subjected to extensive structural modification. With monosubstitution, the para position was most useful in increasing potency, with methyl being preferred. With disubstitution, 2,4-disubstitution further enhanced activity with methyl or cyano groups being preferred at the 2-position. In this series, a benzo-[d][1,3]dioxole group is equivalent to a 4-methyl group in in vitro activity and afforded the compounds with both in vivo activity and moderate half-lives.

Animals↗
PubMed1997

Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist.

Previously we reported the discovery of amidothiophenesulfonamides as endothelin receptor-A antagonists with high potency and selectivity. Replacement of an amide group in this class of compounds with an acetyl group maintained the in vitro binding affinity and in vivo activity while providing a compound with oral bioavailability and longer duration of action. The optimal compound discovered during these studies, 15q (TBC11251), binds competitively to human ETA receptors with a Ki of 0.43 +/- 0.03 nM and an IC50 of 1.4 nM (IC50 for ETB = 9800 nM). This compound inhibits ET-1-induced stimulation of phosphoinositide turnover with a Ki of 0.686 nM and a pA2 of 8.0. The compound has a serum half-life in the rat and the dog of 6-7 h and 60-100% oral bioavailability. This compound is one of the most selective ETA antagonists reported and therefore is suitable for additional pharmacological and clinical investigation of the role of ETA receptors in diseases.

Administration, Oral↗
PubMed1997

Molecular mechanics studies on dipeptide models of diphenylalanine and its derivatives.

As a part of our studies on the structure and conformations of peptidomimetics, we present conformational energy calculations on model peptides with (a) diphenyl alanine and its tricyclic derivatives and (b) triphenyl alanine residues using molecular mechanics and conformational analysis methods. The energies are calculated as a function of the backbone torsions (phi and psi), and the results are presented in terms of isoenergy contours in the phi-psi space. The low-energy models adopt conformations characteristic of a variety of regular structures such as the alpha-helix, gamma-turn and polyproline-II-type three- and four-fold helices. The conformational preferences in the model peptides with diphenyl alanine and its tricyclic derivatives are sensitive to the side-chain torsion, with some similarities to the corresponding preferences of L-Ala dipeptide. The energy profile of the model peptide with triphenyl alanine is similar to that of the model peptide with Tle (tert-leucine) residue. The results of our studies have implications in the design of conformationally constrained peptidomimetics with structures in the beta- and alpha-helical regions.

Dipeptides↗
PubMed1996

Evidence for two tumor suppressor loci associated with proximal chromosome 9p to q and distal chromosome 9q in bladder cancer and the initial screening for GAS1 and PTC mutations.

The most common genetic alteration identified to date in bladder cancer is loss of heterozygosity (LOH) of chromosome 9, suggesting the presence of possible tumor suppressor genes on this chromosome. We attempted to map the location of these genes by analyzing 69 primary transitional cell carcinomas of the bladder with a panel of microsatellite markers for LOH on chromosome 9. Monosomy 9 (defined by LOH of all informative markers analyzed on 9p and 9q) was detected in 26 of 69 (38%) tumors, and 22 of 69 (32%) tumors showed subchromosomal deletions. Twelve tumors (17%) demonstrated partial LOH of chromosome 9 and indicated two distinct regions of LOH. Eight tumors showed distal allelic loss of 9q with a minimal region of common deletion flanked proximally by marker GSN on 9q33. Six tumors showed proximal allelic loss of 9p and 9q with a minimal area of common deletion flanked by markers D9S970 on 9p12 and D9S283 on 9q21. Two tumors showed loss of both the distal region of 9q and the proximal region of 9p and 9q, which were separated by a possible 6-44 cM of retained genetic material. The proximal minimal area of common deletion excluded 9q22.3-q31 to where two putative tumor suppressor genes, the nevoid basal cell carcinoma syndrome and multiple self-healing squamous epithelioma (ESS1) genes, have been mapped. The growth arrest-specific gene (GAS1), a candidate tumor suppressor gene, was included within the proximal minimal region. We evaluated the GAS1 gene for its potential role in bladder cancer using single-strand conformational polymorphism to screen for mutations in GAS1 in 10 bladder cancer cell lines and 14 primary bladder tumors. A polymorphism at codon 88 was noted in one primary bladder tumor, but no other abnormalities were found, suggesting that another potential tumor suppressor gene important to bladder cancer resides in these minimally deleted regions. Because the nevoid basal cell carcinoma syndrome gene has long been speculated to be a putative tumor suppressor gene in bladder cancer and this gene has recently been characterized as the human homologue of the Drosophila patched gene (PTC), 20 primary bladder tumors with chromosome 9q LOH were screened for mutations in PTC using single-strand conformational polymorphism and heteroduplex analysis. No alterations were found in any of the samples analyzed. Furthermore, 4 of 37 noninvasive papillary (Ta) tumors demonstrated loss of all 9q markers with retention of 9p, whereas no Ta tumor showed loss of 9p with retention of all 9q markers, suggesting that LOH of 9q is the earlier event in bladder tumorigenesis. In summary, our results indicate two tumor suppressor loci associated with proximal chromosome 9p to q and distal chromosome 9q that may be important in bladder cancer. GAS1 and PTC do not seem to be frequently mutated in bladder cancer.

Carcinoma, Transitional Cell↗
PubMed1996

Prosthetic rehabilitation of the atrophic maxilla using pre-implant surgery and endosseous implants.

Pre-implant surgery was carried out in 20 patients with advanced atrophy of the edentulous maxilla, using autogenous bone grafts. Endosseous implants were placed after the initial healing period and these were used to retain removable overdentures. Patients were observed for up to 5 years with 15 of the 105 implants placed being lost and two remaining as sleepers. The resulting implant success rate was 84%. Three patients had to return to conventional dentures while the remaining 17 expressed a high degree of satisfaction with their implant retained prostheses. Pre-implant surgery successfully extends the scope for implant therapy by providing sufficient bone for implant placement. The survival rate of implants in these cases appears promising up to 3 years, although further data is required to confirm the effectiveness of this treatment in the long term. Implant retained overdentures are able to successfully restore both oral function and facial form. The rehabilitation of the atrophic, edentulous maxilla remains difficult and complex, even when using pre-implant surgery and implant retained prostheses.

Adult↗
PubMed1996

In-vivo activity and enzymatic hydrolysis of novel prostaglandin F2 alpha prodrugs in ocular tissues.

Enzymatic hydrolysis and in-vivo ocular studies were performed on a novel series of prostaglandin F2 alpha (PGF2 alpha) pivaloyl ester prodrugs to assess their therapeutic potential. These novel PGF2 prodrugs were esterified at the 9-, 11-, and 15-OH positions. Their enzymatic hydrolysis rates were compared to PGF2 alpha 1-isopropyl ester in dog, monkey, and human ocular tissues. Intraocular pressure (IOP) studies were performed in monkeys and dogs, and ocular surface hyperemia was monitored in dogs. PGF2 alpha 9-monopivaloyl ester was not enzymatically hydrolysed in dog and human ocular tissues. PGF2 alpha 11- and 15-monopivaloyl esters and PGF2 alpha 11,15-dipivaloyl ester were converted to PGF2 alpha by all ocular tissues at a substantially slower rate than PGF2 alpha l-isopropyl ester. Despite their slow enzymatic hydrolysis rates, the ocular hypotensive activity of PGF2 alpha mono and dipivaloyl esters, where positions 11- and 15- were functionalized, closely approached the activity achieved with PGF2 alpha l-isopropyl ester. The degree of ocular surface hyperemia associated with PGF2 alpha 11-pivaloyl ester and PGF2 alpha 11,15-dipivaloyl ester was less than that associated with equivalent doses of PGF2 alpha l-isopropyl ester. It appears that rapid enzymatic hydrolysis rates are not necessary to obtain efficacious ocular hypotensive PGF2 alpha ester prodrugs. Slow enzymatic hydrolysis rates may assist in reducing the degree of ocular surface hyperemia. A further contributory factor in this regard could be the approximately ten-fold favorable difference in enzymatic hydrolysis rates between iris-ciliary body and conjunctival tissue for these novel pivaloyl esters of PGF2 alpha. These factors appear to translate into an improved therapeutic index for separating ocular hypotensive and ocular surface hyperemic effects.

Animals↗