Biomedical subjects

S Y Loh

Publications and source records attributed to S Y Loh.

11 recordsLinked to original sources

PubMed2005

Tarsometatarsal joint injuries--review of clinical presentation and surgical treatment.

The tarsometatarsal (Lisfranc) joint suffers a spectrum of injuries ranging from solely ligamentous injury to fracture dislocation. The authors evaluated eighteen consecutive patients who underwent surgery for tarsometatarsal joint injuries, utilising 4.5 mm cancellous screws and 1.6 mm K-wires. The outcome of function and anatomical reduction were assessed by AOFAS (American Orthopedic Foot and Ankle Society) midfoot score and radiography. Patients with only ligamentous injury scored poorer partly due to delay in diagnosis and the nature of the injury. The technique used maintained anatomical reduction at the time of review.

Adult↗

PubMed2004

Reliability and validity of the Pressure Management Inventory in a Malaysian population.

There is a general lack of valid tools to measure work stress of Malaysian. This study examines the validity and reliability of the Pressure Management Inventory (PMI). Reliability was evaluated using test retest method, and its correlation coefficient was calculated using Pearson's r. Internal consistencies were examined using Cronbach's Alpha. For precision, the Intraclass coefficients (ICC) were calculated for all the scales. Face Validity and Content Validity were assessed using an open-ended questionnaire on 6 content experts (psychiatrists in HKL). The results show good internal consistencies (alpha < or = 0.7) for most subscales, with the best results in the 'Pressure Scale'. The weak scales are 'Individual-Differences' scale and 'Social Support' scale. The test-retest correlation coefficients were significant at the level of p<0.001 for all, except one scale. The ICC coefficients were high (>0.7) for most scales, particularly for Pressure, Health and Coping Scales. The PMI is a suitable, reliable and valid tool to measure stress of Malaysians. More in-depth study with a wider sampling needs to be carried out to add confidence of its usage on Malaysians.

Adolescent↗

PubMed2002

Profile of women presenting for abortions in Singapore at the National University Hospital.

The study was conducted to profile women seeking abortions at the National University Hospital, with particular interest in the trend of teenage pregnancies with the aim of identifying risk factors for late presentation for abortions. All patients who underwent an abortion at our center from January 1, 1996 to December 31, 2000 were recruited. Data were entered into a prepared questionnaire during the mandatory pre-abortion counseling sessions and completed at the 6-week post-abortion follow-up. This was then keyed into a database (SPSS Version 10), and the results were analyzed. Multivariate analysis was used in identifying risk factors associated with late presentation for abortions. Chi-square analysis of variables was used where relevant. A total of 1370 women presented for induced abortions during the period of study. The mean age of women was 29.6 years. Most women were either homemakers (35.3%) or semi-skilled workers (28.5%) with at least a secondary school education (58.3%). The majority were married (75.5%). There was a significant trend in the proportion of single women seeking abortions, from 18.3% in 1996 to 27.8% in 2000 (p < 0.05). At the same time, the proportion of women presenting for repeat abortions also increased from 13.8% in 1996 to 33.2% in 2000 (p < 0.05). Teenage abortions made up 117 (8.5%) of the study group, of which 95% were single women. Significant proportions (52.1%) were students at the time of abortion. In contrast to women above 20 years of age, pregnant teenagers were more likely not to have used any contraception (67.1% vs. 37.3%) and more likely to present late for abortion (18.8% vs. 10.4%). Teenage pregnancies are a major risk factor for late presentation for abortions. This emphasizes the need for availability and easy access to early abortion counseling, and the need for sex education with use of contraception starting in schools, to reduce abortions among teenagers.

Abortion, Induced↗

PubMed1999

Unknown identification using reference mass spectra. Quality evaluation of databases.

The high success of the "uncertified" mass spectrometry spectral collection started in 1956 demonstrated qualitatively that a partial reference mass spectrum, even one measured routinely, can be of real value. Correct matchings were still possible despite reference errors, which almost never led to close matches that were incorrect. This study shows quantitatively that the number of different compounds, not the number of peaks in a spectrum, is by far the most important determinant of database efficiency for identifying a "global" unknown. A statistical evaluation of matching performance shows that only 6, 12, and 18 peaks in a reference spectrum are 13%, 67%, and 96%, respectively, as valuable as hundreds of peaks. Also, a separately measured second spectrum of the same compound is 50% as valuable as the first. Database expansion that tripled the number of possible wrong answers only reduced the proportion of correct identifications by 5%. Corrections of a mass or abundance error in each of six reference spectra increase the database matching performance by as much as the addition of one spectrum of a new compound. A new "matching quality index" based statistically on these values indicates that the largest database is also by far the most effective for matching unknowns.

Animals↗

PubMed1998

Comparison of algorithms and databases for matching unknown mass spectra.

The most used algorithms for the identification of electron-ionization mass spectra are INCOS and probability based matching (PBM). For unknown spectra of high purity, approximately 75% of rank 1 answers are correct for both algorithms, matched against the National Institute of Standards and Technology 62,235 spectrum database. With matching criteria that retrieve 50% of the possible correct answers from the Wiley 228,998 spectrum database, 54% of the PBM and 42% of the INCOS answers are correct; for 85% purity unknowns, 48% and 27% are correct. For an unknown spectrum of two compounds, neither was reported in the first three INCOS answers; eight of the first ten PBM answers identify both components.

Algorithms↗

PubMed1993

Effect of buthionine sulfoximine on PtII and PtIV drug accumulation and the formation of glutathione conjugates in human ovarian-carcinoma cell lines.

Glutathione (GSH) has often been implicated in the mechanism of resistance to platinum anti-cancer drugs. It has been suggested that GSH may reduce the cytotoxicity of these drugs by forming inactive conjugates and by enhancing the repair of DNA-platinum crosslinks. In the present study we have examined the effect of D,L-buthionine-S,R-sulfoximine (BSO) pretreatment on the accumulation of platinum in a sensitive (CHI) and 2 relatively resistant (SKOV-3, HX/62) human ovarian-carcinoma cell lines following exposure to PtII- (cisplatin, carboplatin) and PtIV-drugs (tetraplatin). The metabolism of cisplatin and tetraplatin (particularly the extent of platinum-GSH conjugate formation) in the presence and absence of BSO pre-treatment was also examined in these cell lines. BSO pre-treatment reduced the accumulation of PtII but not that of PtIV drugs in the relatively resistant SKOV-3 and HX/62 cell lines. It had no effect on the accumulation of either class of drugs in the sensitive CHI cells. Metabolism studies with cisplatin showed that the SKOV-3 and HX/62 cells, which contained 2- to 3-fold higher levels of GSH, were able to inactivate a greater proportion of cellular cisplatin, by the formation of platinum-GSH conjugates, than the CHI cells. A significant inhibition in formation of these conjugates, by BSO-induced depletion of cellular GSH (over 80%), did not, however, increase cisplatin concentration in the resistant cells. In contrast, a small increase in cisplatin concentration was observed in the sensitive cells following BSO pre-treatment. Comparison of cisplatin and tetraplatin metabolism in the SKOV-3 cells indicated that a greater proportion of the latter drug was inactivated by formation of GSH conjugates. BSO-induced depletion of cellular GSH in this cell line significantly reduced the formation of such conjugates from both drugs. However, concomitant increases in intracellular levels of reactive species were observed only after tetraplatin exposure. Our data suggest that the greater potentiation of PtIV- compared with PtII-drug cytotoxicity in the relatively resistant cell lines following 24 hr BSO pre-treatment may be caused by a differential effect of BSO on the metabolism and cellular distribution of these drugs. A BSO-induced reduction in PtII- but not PtIV-drug accumulation in these cells may also partially contribute to the differential potentiation of cytotoxicity of these drugs.

Antimetabolites, Antineoplastic↗

PubMed1992

Comparison of cellular accumulation and cytotoxicity of cisplatin with that of tetraplatin and amminedibutyratodichloro(cyclohexylamine)platinum(IV) (JM221) in human ovarian carcinoma cell lines.

We have compared the cellular accumulation and cytotoxicity of three platinum compounds in a panel of five human ovarian carcinoma cell lines. The cell lines, which were established from both untreated and pretreated patients, showed a wide range in sensitivity to cisplatin and other platinum drugs. The panel consisted of two sensitive (41M, CH1), one in vivo acquired resistant (PXN/94) with moderate sensitivity, and two intrinsically resistant (SKOV-3, HX/62) cell lines. The cisplatin 2-h concentration of drug required to inhibit cell growth by 50% compared with vehicle treated control cells (IC50 values) for these cell lines were in the following order: CH1 < 41M < PXN/94 < SKOV-3 < HX/62. None of the cell lines showed saturation of platinum accumulation (per mg protein) at 2 h after exposure to cisplatin concentrations of up to 500 microM. The highest cellular platinum accumulation was observed in the sensitive 41M cell line which was established from an untreated patient. The lowest accumulation was found in the intrinsically resistant HX/62 cell line. The rate of platinum accumulation at an equimolar concentration of cisplatin was 41M > SKOV-3 > CH1 > PXN/94 > HX/62. The relationship between drug accumulation and cytotoxicity was evaluated by comparing 2-h IC50 values with platinum accumulation following exposure to both equimolar and equitoxic doses of the agent. The results suggest that reduced drug accumulation may play a partial role in the mechanism of intrinsic resistance to cisplatin in one cell line (SKOV-3) and a major role in another (HX/62), where reduced accumulation is attributable to reduced uptake rather than enhanced efflux. Decreased drug accumulation may also contribute significantly to the lower sensitivity of the PXN/94 cell line to cisplatin. Interestingly, both the PXN/94 and the sensitive CH1 cell lines, which were established from patients pretreated with platinum drugs, showed reduced drug accumulation relative to the 41M cell line. Cellular accumulation of tetraplatin and JM221 [(ammine)dibutyratodichloro(cyclohexylamine)platinum(IV)], a novel platinum(IV) dicarboxylate complex exhibiting enhanced cytotoxicity compared to cisplatin, was also examined. Comparison with platinum accumulation from cisplatin suggests that the increased cytotoxicity of tetraplatin and JM221 may be related to their increased accumulation. Significantly both agents are more lipophilic than cisplatin, which may account partially for their improved uptake in cisplatin resistant cells.

Antineoplastic Agents↗

PubMed1992

Mechanism-related circumvention of acquired cis-diamminedichloroplatinum(II) resistance using two pairs of human ovarian carcinoma cell lines by ammine/amine platinum(IV) dicarboxylates.

Acquired resistance to cisplatin has been generated in vitro in two human ovarian carcinoma cell lines: 41M, established from a previously untreated patient; and CH1, from a patient previously treated with cisplatin and cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (carboplatin). In neither cell line with acquired resistance did intracellular detoxification (via increased glutathione or metallothioneins) appear to be a major determinant of resistance. Resistance in 41McisR (resistance factor of 4.7) appeared to be due predominantly to a reduced platinum accumulation (levels were only 23.8% in 41McisR versus 41M). This was also reflected at the DNA level by a similar level of reduced DNA interstrand cross-links and total platinum-DNA adducts measured immediately after a 2-h exposure to cisplatin in 41McisR versus 41M. Conversely, for CH1cisR (resistance factor of 6.5), platinum accumulation, and initial numbers of DNA-interstrand cross-links and total DNA-platinum adducts were not significantly different from the parent CH1 line. This is suggestive of a resistance mechanism involving increased DNA repair or tolerance to platinum-DNA adducts operating in the CH1cisR/CH1 pair of lines. Cross-resistance to carboplatin and partial cross-resistance to the 1,2-diaminocyclohexane-containing agent, (trans-d,l)-1,2-diaminocyclohexane tetrachloroplatinum(IV) (tetraplatin), was observed in both pairs. However, two novel platinum(IV) ammine/amine dicarboxylates, ammine dibutyratodichloro(cyclohexylamine)platinum(IV) (JM221) and ammine dibenzoatodichloro(propylamine)platinum(IV) (JM244), completely circumvented resistance in 41McisR to produce some collateral sensitivity (resistance factors of 0.67 and 0.54, respectively) but showed cross-resistance in CH1cisR (resistance factors of 3.7 and 4.6). In contrast to the data for cisplatin, intracellular platinum levels were not significantly different between the 41M and 41McisR pair of cell lines after exposure to JM244. These results suggest that the ammine/amine platinum(IV) dicarboxylates, which show considerably greater in vitro cytotoxicity than cisplatin, are capable of circumventing acquired cisplatin resistance which is due to decreased intracellular accumulation but are not able to overcome resistance at the level of DNA platination and removal.

Antineoplastic Agents↗

PubMed1992

Establishment and characterization of an in vitro model of acquired resistance to cisplatin in a human testicular nonseminomatous germ cell line.

Clinically, human testicular nonseminomatous germ cell tumors exhibit remarkable sensitivity to platinum-based chemotherapy. To define better the mechanistic basis for this unusual sensitivity, the biochemical determinants of platinum-induced cytotoxicity have been investigated in a human testicular tumor cell line (GCT27) established from a previously untreated patient and in an in vitro derived 5.6-fold cisplatin-resistant stable variant (GCT27cisR). Compared to 12 ovarian and 5 cervical human tumor cell lines, the parent GCT27 line was among the most sensitive to the cytotoxic effects of both cisplatin (dosage producing 50% inhibition, 0.2 microM) and carboplatin (dosage producing 50% inhibition, 2.9 microM), thus reflecting clinical data. A 4-day exposure sulforhodamine B-staining assay was used to determine that GCT27cisR was cross-resistant to carboplatin and iproplatin and the classical bifunctional alkylating agents melphalan and chlorambucil. Partial cross-resistance was observed to tetraplatin, methotrexate, and mitomycin C. No cross-resistance was observed to Adriamycin, etoposide, vinblastine, bleomycin, 1-beta-D-arabinofuranosylcytosine, and 5-fluorouracil. Intracellular cisplatin accumulation across the dose range 2.5-100 microM (for 2 h) was 1.6 +/- 0.39-fold (mean +/- SD) greater for the parent line. There was no significant difference in glutathione levels between the two lines. The acquired resistance line was 1.9-fold more resistant than the parent line to the cytotoxic effects of cadmium chloride. There was no significant difference between the two lines, however, in the total amounts of platinum bound to DNA after cisplatin exposure (25, 50, or 100 microM for 2 h). The removal of total platinum adducts from DNA was significantly faster for GCT27cisR compared to the parent line (half-times of removal, 32 and 67 h, respectively). These data suggest that the abnormal sensitivity of the parent testicular tumor cell line to platinum-containing anticancer drugs may be due predominantly to an inherent defect in the ability of these cells to remove platinum from their DNA. This defect is apparently lost in the acquired resistance counterpart. Reduced intracellular accumulation and increased cytoplasmic concentrations of metallothionein may also contribute, in part, to the acquisition of cisplatin resistance in this model.

Antineoplastic Agents↗

PubMed1992

Reduced drug accumulation as a major mechanism of acquired resistance to cisplatin in a human ovarian carcinoma cell line: circumvention studies using novel platinum (II) and (IV) ammine/amine complexes.

Acquired resistance to cisplatin (cis-diamminedichloroplatinum (II)) has been generated in vitro in the 41M human ovarian carcinoma cell line, established from a previously untreated patient. Three cisplatin-resistant variants were selected at approximately 2, 4 and 6-fold resistance (in terms of 50% inhibitory concentrations), in order to study the underlying mechanisms of acquired cisplatin resistance. Compared to the parent line, platinum accumulation following exposure to equimolar concentrations of cisplatin was on average (across the entire concentration range) 2.9, 3.6 and 4.8-fold lower in the 41McisR2, 41McisR4 and 41McisR6 cell lines, respectively. Thus the difference in uptake corresponded closely with their resistance factor in the three resistant variants. Moreover, a significant reduction in platinum accumulation was observed as early as 5 min after exposure to cisplatin in the 41M vs 41McisR6 cell lines. Platinum accumulation was similar in all cell lines following exposure to equitoxic concentrations (2 h IC50) of cisplatin. Enhanced efflux of drug was not observed between the 41M and 41McisR6 cells. In addition, there was no difference in intracellular glutathione (GSH) levels. Our previous studies have shown no indication of metallothionein involvement and the decrease in cisplatin uptake in the 41McisR6 cells was reflected by a similar reduction in DNA interstrand cross-links (ISC) formation. These results suggest that the mechanism of acquired resistance to cisplatin in the 41McisR6 cell line may be predominantly due to reduced drug uptake. The 41McisR6 cells were not found to be cross-resistant to ouabain, a postulated specific inhibitor of sodium-potassium adenosine triphosphatase (Na+, K(+)-ATPase), suggesting that decreased cisplatin accumulation in these cells is probably not regulated by alterations in their Na+, K(+)-ATPase levels, and Na+ potential across the plasma membrane. Cellular accumulation of a novel class of platinum (IV) ammine/cyclohexylamine dicarboxylates, which exhibit enhanced cytotoxicity over cisplatin and completely circumvent resistance to cisplatin in the 41McisR line, was also examined. The data suggests that increased accumulation of these compounds, as a result of their enhanced lipophilicity, could account for the dramatic increase in their potency over cisplatin.

Carcinoma↗

PubMed1990

Hadamard transform measurement of tandem Fourier-transform mass spectra.

The simultaneous collection of multiple spectra using tandem (MS/MS) and multidimensional (MS/MS/MS) mass spectrometry from multiple precursors is demonstrated to yield correspondingly enhanced sensitivity. This approach utilizes Hadamard transform deconvolution and takes advantage of the multichannel dissociation capability of Fourier-transform mass spectrometry. By application of this to an 11-component mixture, the 11 spectra of the products of dissociating 11 different combinations of six of the component molecular ions are measured; Hadamard transformation yields individual spectra of the precursor ions exhibiting a signal-to-noise improvement of 1.8x over spectra measured separately, as predicted by theory. Precursor ion selection with high specificity and product formation with high abundance reproducibility are critical; spurious peaks resulting from imperfect reproducibility can be minimized by using simultaneous equation coefficients reflecting the degree of precursor dissociation. Extension of this technique to MSn spectra is demonstrated with simultaneous MS/MS/MS monitoring of three precursors and three daughters yielding nine spectra representing the nine possible dissociation pathways. For MSn spectra, coding the product relationships for each additional step (e.g., precursor----daughter, daughter----granddaughter) requires elimination of half of the remaining ions. No ions are lost for coding in an improved Hadamard approach in which the combined daughter spectrum of the selected half of the precursors is subtracted from that of the other half.

Fourier Analysis↗