Biomedical subjects

M F Chan

Publications and source records attributed to M F Chan.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1996

Synthesis and conformational analysis of cyclic pentapeptide endothelin antagonists.

Two endothelin antagonists cyclo(D-Leu-D-Val-Pro-D-Asp-Trp) (IPI-147), and cyclo (D-Trp-D-Asp-Ac3c-D-Val-Leu) (IPI-725) have been synthetized. Their solution conformations have been studied in aqueous solution by NMR spectroscopy and dynamics simulation. Activity studies show that IPI-725 is a strong ETA antagonist, while IPI-147 is a weak ETA antagonist. Comparison of the solution conformations of these two ETA antagonists suggests that the difference in their activities results from their structural differences. IPI-147 contains a type II beta-turn with a hydrogen bond between NH of D-Val and the C = O of D-Asp. IPI-725, on the other hand, contains two turns, a type II beta-turn with a hydrogen bond between NH of D-Asp and C = O of D-Val, as well as a gamma'-turn with a hydrogen bond formed between D-Val NH and D-Asp carbonyl group. Therefore IPI-147 appears to be more flexible than IPI-725. Although both beta-turns contain the same residues, their orders in the turn are reversed. The beta-turn in IPI-725 is formed with D-Val:Leu:D-Trp:D-Asp, while in IPI-147, the beta-turn is formed with D-Asp:Trp:D-Leu:D-Val. The activities and solution conformations of IPI-147 and IPI-725 were also compared with BQ-123 [cyclo(D-Trp-D-Asp-Pro-D-Val-Leu)], a well characterized, highly potent endothelin antagonist.

Endothelins↗

PubMed1996

Complications of upper gastrointestinal endoscopy.

Complications of upper gastrointestinal endoscopy are uncommon. Approximately one complication occurs with every 1000 procedures. The mortality rate is estimated to be between 0.5 and 3 per 10,000 cases. Cardiopulmonary events comprise 50% of all major complications, and most of these events result from the medications used for conscious sedation. Diagnosis, treatment, and prevention of common complications are discussed; rare complications are mentioned.

Endoscopy, Digestive System↗

PubMed1996

A retrospective study of the maintenance requirements associated with implant stabilised mandibular overdentures.

The maintenance requirements of a group of 58 patients, treated with the IMZ osseointegrated implant system and mandibular overdentures were investigated. Prostheses were retained by either bar and clip or separate stud attachments. The patients were followed up regularly for periods of between one and six years. The median number of maintenance procedures required per patient per year varied between 1-5. Detailed examination of the data revealed that a wide range of maintenance procedures was required, including replacement prostheses in 46% of cases. There were some differences related to the retentive elements used for the prostheses.

Adult↗

PubMed1995

Prosthetic management of the atrophic mandible using endosseous implants and overdentures: a six year review.

This paper presents the treatment results and experiences gained from a retrospective study of patients treated with the IMZ osseo-integrated implant system and mandibular overdentures. Patients experiencing problems wearing conventional dentures were assessed by the implant team and 65 cases were treated with 154 endosseous implants placed in the edentulous mandible. Two to four implants were placed in each case and in addition some patients have had augmentation of the mandible with hydroxyapatite. The definitive mandibular prostheses were supported by both implants and the residual ridges. A variety of retention systems were utilised, which included different types of bar and clip, stud attachments, and magnets. The patients have been followed up regularly and evaluated after periods of between one and six years. Six implants have failed over this time resulting in a success rate of over 96%. Most patients expressed a high degree of satisfaction with their new overdentures. There was, however, a considerable burden of maintenance care required for the patient group examined. The findings demonstrate that implant retained overdentures offer a highly effective means of oral rehabilitation for the atrophic mandible, restoring both oral function and facial form.

Adult↗

PubMed1995

Long-term follow-up of endoscopic retrograde cholangiopancreatography sphincterotomy for patients with acquired immune deficiency syndrome papillary stenosis.

PURPOSE: To evaluate the long-term effects on biliary-type pain and changes in biochemical parameters in patients with AIDS-associated papillary stenosis who underwent endoscopic retrograde cholangiopancreatography (ERCP) sphincterotomy. PATIENTS AND METHODS: Twenty-five consecutive patients were diagnosed by cholangiography with AIDS-associated papillary stenosis using standard criteria. Patients underwent ERCP sphincterotomy and were followed prospectively in the Gastrointestinal or Liver Clinics, San Francisco General Hospital, and by their primary physicians. Post-procedure data was prospectively collected by chart review or in-person or telephone interview, and analyzed using statistical software. RESULTS: All patients presented with severe right upper quadrant and/or mid-epigastric abdominal pain and had marked elevations of serum alkaline phosphatase. Following ERCP sphincterotomy, pain scores decreased significantly for at least 9 months of follow-up. Serum alkaline phosphatase levels, however, remained essentially unchanged. Overall quality of life was difficult to assess, as patients suffered from other AIDS-associated debilitating diseases. CONCLUSIONS: ERCP sphincterotomy, while not without risks, provided significant reduction in pain in patients with AIDS-associated papillary stenosis.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Conformational studies on model dipeptides of Gly, L-Ala and their C alpha-substituted analogs.

As a part of the development of conformational guidelines for the design of metabolically altered peptidomimetics, we present conformational energy calculations on model dipeptide compounds with glycine (Gly), L-alanine (Ala), alpha-aminoisobutyric acid (Aib), L-tert-butylglycine (Tle), L-phenylglycine (Phg), (alpha, alpha)-diphenylglycine (D phi g), L-2-aminobutyric acid (Abu), 2-amino-2-ethylbutyric acid (Deg), L-2-amino-2-vinylacetic acid (Ava) and (alpha, alpha)-divinylglycine (Dvg). The energy calculations have been made using molecular mechanics methods with a force field derived from MM2. The salient features are expressed in terms of conformational energy plots, drawn as a function of the backbone torsion angles phi(Ci'-1-Ni-Ci alpha i-Ci') and psi(Ni-Ci alpha -C'-N(i+1)). The low-energy structures of these compounds are qualitatively consistent with the X-ray crystal structure analyses of peptides and peptidomimetics. They are also in agreement with the results of the solution-phase studies carried out by NMR and IR techniques. The results obtained have important implications in the design of conformationally restricted peptidomimetics.

Alanine↗

PubMed1995

Verification of water equivalence of FeMRI gels using Monte Carlo simulation.

Dosimetric characteristics of the FeMRI gels for various energy photon and electron beams were investigated using the Integrated Tiger Series (ITS) Monte Carlo codes. The FeMRI gels have been reported as being tissue-substitutes which can be shaped to any desired contour for three-dimensional (3D) mapping of dose distribution using magnetic resonance (MR) scanning. This study indicated that the central axis depth dose, off-axis depth dose, transverse profile at the depth of 50% of maximum dose, and energy deposition for photons and electrons in the gels are close to those in water. From these comparisons, it is concluded that FeMRI gels are suitable substitutes for water for the purposes of dose measurements of both photons and electrons used in radiotherapy.

Electrons↗

PubMed1995

Confirmation of target localization and dosimetry for 3D conformal radiotherapy treatment planning by MR imaging of a ferrous sulfate gel head phantom.

A detailed methodology has been developed to verify the three-dimensional (3D) radiation dose mapping of conformal therapy radiation treatment planning by FeMRI dosimetry. A phantom that consisted of a human skull filled with a 1-mM solution of ferrous sulfate and 0.1-N sulfuric acid gelled with 7.5% (by weight) gelatin was employed. With a spherical target volume in the head phantom, five noncoplanar conformal beams were designed through the use of a 3D treatment planning system developed in-house. The phantom was irradiated with a 6-MV linear accelerator to a total dose of 25 Gy delivered to the periphery of the target volume. The phantom and a set of calibration vials were scanned simultaneously in a GE 1.5T MR imager with six different multiscan inversion-recovery pulse sequences. The values of T1 were evaluated on a pixel-by-pixel basis through the use of custom-built software on a UNIX workstation and were converted to dose using calibration data. Comparisons of dose distributions between those measured by FeMRI and those calculated by 3D treatment planning show good agreement.

Biophysical Phenomena↗

PubMed1994

Ameloblastoma of attached gingiva.

A case of a rare extra-osseous ameloblastoma is presented. It meets identical histological criteria as intra-osseous ameloblastoma, but its clinical presentation and behaviour are very different. It is non-invasive and may be locally excised without recurrence.

Ameloblastoma↗

PubMed1994

Identification of a new class of ETA selective endothelin antagonists by pharmacophore directed screening.

Novel endothelin antagonists were identified through a "pharmacophore directed screening" strategy. The sulfanilamide antibacterial agent sulfisoxazole was found to be a good endothelin receptor antagonist (IC50's of 0.60 microM and 22 microM for the ETA and ETB receptors, respectively). The structurally similar sulfamethoxazole was found to be a weaker antagonist (IC50 for ETA 16 microM and for ETB 230 microM). These compounds represent a new class of low molecular weight and ETA-selective non-peptide endothelin antagonists.

Cell Line↗

PubMed1994

Significance of thermal cycling in microleakage analysis of root restorations.

Root surface cavities prepared in extracted premolars were restored with a selection of restorative materials. Prior to eosin dye immersion, one group of teeth was kept at constant temperature whilst another group underwent thermal cycling. The teeth were sectioned transversely through the restorations and an assessment of the degree of microleakage was used to compare the sealing ability of the selected materials. Eosin dye was able to discriminate more effectively between the microleakage behaviour of the restorative materials when samples were kept at a constant temperature.

Chemical Phenomena↗