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Biomedical subjects

C Chan

Publications and source records attributed to C Chan.

At least 145 records · Page 8Linked to original sources
PubMed1997

Changing indications for penetrating keratoplasty: a newly developed country's experience.

PURPOSE: To study the changing indications for penetrating keratoplasty in Singapore and compare local indications with developed countries with established corneal graft programs. METHODS: A descriptive study of all penetrating keratoplasty cases performed in the Singapore National Eye Center over a 5 year period, from 1 January 1991 to 31 December 1995 using records of the Singapore Eye Bank registry. RESULTS: A total of 327 penetrating keratoplasties were performed. Bullous keratopathy was the indication in more than a quarter of all cases (26.3%). Aphakic bullous keratopathy (11.6%) and pseudophakic bullous keratopathy (11.3%) accounted for the majority of the bullous keratopathy cases. The other leading indications were regrafts (11.9%), corneal dystrophies (10.4%), traumatic scarring (10.1%) and keratoconus (9.8%). A higher proportion of aphakic and pseudophakic bullous keratopathy as well as regrafts was noted in this series compared to a previous report on corneal transplantation in the 1980s. A rising indication rate of pseudophakic bullous keratopathy, in conjunction with a declining indication rate of herpetic keratitis was observed over the 5 year study period. CONCLUSIONS: The indications for penetrating keratoplasty in Singapore appear to follow the trend seen in developed Western countries over the past few decades.

Adolescent↗
PubMed1997

Determinants of peak bone mass in Chinese women aged 21-40 years. III. Physical activity and bone mineral density.

Previous studies on the relation between moderate physical activity and bone mass have observed conflicting results. Many of these studies have not dissociated the role of physical activity by age groups and in relation to the period of peak bone mass formation. Our cross-sectional analysis of the baseline data of a longitudinal study of 273 women aged 21-40 attempted to evaluate the role of moderate physical activity on bone mass around the period of peak bone mass attainment. The analyses were carried out separately for the two age groups--21-30 and 31-40--and had also taken into account the effects of age, dietary calcium intake, and lean body mass on bone mineral density (BMD). The total metabolic equivalent values (MET) of leisure time physical activity was based on the MET values for each activity and the reported time spent on each activity in the past year. The results indicated that among the younger group of women, high level of leisure time physical activity was associated with higher bone mass at both the spine and the hip. Additive effects of physical activity and dietary calcium intake on the spine and the hip BMD were observed. Together with age and lean body mass, physical activity and dietary calcium intake accounted for 19% of the variances of bone mineral at the spine and 9-11% at the hip. Among women aged 31-40, presumably after the peak bone mass formation, lean body mass as well as fat mass have independent strong association with BMD. Physical activity was not associated with bone mass in this age group.

Absorptiometry, Photon↗
PubMed1997

The effect of sampling error and measurement error and its correlation on the estimation of multi-locus fixed-bin VNTR RFLP genotype probabilities.

Bootstrapping was used to examine the effect of sampling error and measurement error and its correlation on fixed-bin genotype probabilities. Bootstrap confidence intervals (Cls) were made relative to the point estimate using the log of the inverse of the probabilities. From databases of 200-250 genotypes, sampling error alone yielded median relative 95% CIs of from one order of magnitude out of five for one locus to one out of ten for four loci. Measurement error of the test genotype fragments increased the latter to about one order of magnitude out of eight. Database measurement error and its correlation had only a slight effect on multi-locus probability uncertainty. Together, these uncertainties are several orders of magnitude greater than error due to population substructuring of a race by its major component ethnic groups.

Confidence Intervals↗
PubMed1997

Evaluating the FONE FIM: Part I. Construct validity.

Rasch analysis was used in this paper to evaluate the Motor component of the FONE FIM, the telephone version of the Functional Independence Measure (FIM). For this purpose, 132 patients discharged from an inpatient geriatric assessment and rehabilitation program were assessed by trained research assistants using the FONE FIM. The results at 5 weeks post-discharge were compared to the observation FIMs (OBS FIMs) done at home 6 weeks post-discharge. These patients had an average age of 79 years and presented with multiple, complex medical problems and significant functional decline. The FONE FIM and the OBS FIM were shown to share a strikingly similar item hierarchy, based on Rasch item difficulty measures. Only bladder management and climbing stairs were misfitting items as indicated by item fit statistics. The same 13-item set and 4-point scales were shown to be psychometrically optimal for both the FONE FIM and the OBS FIM based on the person separation index. Further research is required to address the issue of the optimal item set and scale levels from psychometric and clinical perspectives.

Activities of Daily Living↗
PubMed1997

Evaluating the FONE FIM: Part II. Concurrent validity & influencing factors.

The "motor" (activities of daily living) component of the FONE FIM, the telephone version of the Functional Independence Measure (FIM) was evaluated in a cohort of 132 patients who had been discharged to home from a geriatric inpatient assessment and rehabilitation program. In the current study, Rasch person ability measures were derived from telephone assessments 5 weeks after discharge and in-home assessments 1 week later. Concordance between the modes was shown to be satisfactory for the Rasch measures based on intraclass correlation coefficients. However, the telephone mode consistently generated lower estimates than did the observational mode. This was due to the fact that the telephone mode underestimated motor function for the majority of patients who were at higher levels of cognition and motor function, but overestimated for patients who were at lower levels of cognition and motor function. At the item level, concordance, as determined by Kappa statistics, was better when the FONE FIM responses came from the patient rather than proxy respondents, and when the assessments were done by more experienced rather than less experienced raters. Based on these findings, a mixed strategy, the telephone mode for patients capable of responding to the FONE FIM and in-home assessments for those who are incapable, is recommended.

Activities of Daily Living↗
PubMed1996

Analysis of the megakaryocyte glycoprotein IX promoter identifies positive and negative regulatory domains and functional GATA and Ets sites.

The glycoprotein (GP) Ib-V-IX multisubunit complex binds to von Willebrand factor and mediates the adhesion of platelets to the subendothelium of damaged blood vessels. Expression of the GPIX subunit is required for stability of the complex, and its absence in platelets is associated with the rare bleeding disorder Bernard-Soulier syndrome. Comparative analyses indicate that the four GPIb-V-IX subunits are members of the leucine-rich repeat family and suggest that GPIX resembles a possible primitive progenitor of this group. To characterize GPIX transcriptional regulation, a series of 5' deletion constructs was made linking the GPIX upstream flanking sequence to the luciferase marker gene, and promoter activity was measured in transiently transfected human erythroleukemia cells. This analysis identified two negative regulatory domains between -686 to -423 and -311 to -203 and two positive regulatory domains at -323 to -311 and -151 to -100 relative to the GPIX transcription start site. In addition, site-directed mutagenesis experiments and in vitro gel retardation assays identified Ets and GATA elements at -42 and -65, which positively regulate GPIX promoter activity and specifically bind nuclear factors derived from human erythroleukemia cells. DNase I protection experiments identified a protein-dependent "footprint" and hypersensitive site within the GPIX Ets sequence. These results provide a framework for comparison of the GPIX promoter with others of the GPIb-V-IX system, other megakaryocyte-specific genes, and other members of the leucine-rich repeat family.

Base Sequence↗
PubMed1996

Isolation and characterization of soluble electron transfer proteins from Chromatium purpuratum.

Several soluble electron transfer proteins were isolated and characterized from the marine purple-sulfur bacterium Chromatium purpuratum. The C. purpuratum flavocytochrome c is similar in molecular mass (68 kDa) and isoelectric point (6.5) to flavocytochromes isolated from other phototrophs. Redox titrations of the flavocytochrome c hemes show two components with midpoint potential values of +15 and -120 mV, behavior similar to that observed with the flavocytochrome isolated from the thermophilic Chromatium tepidum. Moreover, N-terminal amino acid sequence analysis of both the flavin and the cytochrome subunit indicates substantial homology to the primary structure of the flavocytochrome c of Chromatium vinosum. In contrast, the C. purpuratum high-potential iron-sulfur protein (HiPIP) differs from those isolated from other photosynthetic bacteria in its relatively high midpoint potential (+390 mV) and the possibility that it exists as a dimer in solution. Two low molecular mass c-type cytochromes were also characterized. One appears to be a high-potential (+310 mV) c8-type cytochrome. Amino acid sequencing suggests that the second cytochrome may be a homologue of the low-potential cytochrome c-551, previously described in two species of Ectothiorhodospirillaceae.

Amino Acid Sequence↗
PubMed1996

Effects of prolonged sequential balloon inflations on results of coronary angioplasty.

In percutaneous transluminal coronary angioplasty (PTCA), prolonged balloon inflations using perfusion balloon catheters have shown a higher procedural success rate and fewer in-hospital complications than short balloon inflations. However, perfusion balloons have well-recognized limits for routine use. This study assessed the effects of a prolonged cumulative occlusion time obtained with sequential balloon inflations using a routine balloon catheter, applicable to all lesions, and compared these results with those obtained with standard short balloon inflations. Three hundred ten lesions (in 289 patients) were randomized to either standard (3 to 5 inflations < or = 1 minute each; n = 161) or prolonged (3 to 5 inflations of 3 to 5 minutes each; n = 149) balloon inflations. Angiographic success (residual stenosis <50% and no dissection > or = D1) was assessed at the end of this "protocol" phase. Further dilatation was performed if required ("adjunctive" phase). Systematic repeat catheterization was scheduled 4 to 6 months later. Cumulative inflation time was 198 +/- 58 seconds in the "standard" group versus 782 +/- 303 seconds in the "prolonged" group. At the end of the protocol phase, the success rate was higher after prolonged than after standard dilatation (92% vs 80%; p <0.002), with less frequent dissections (14% vs 30%; p = 0.0009). At the end of the adjunctive phase, required for 12 patients in the prolonged group and 32 patients in the standard group (p = 0.003), results were comparable in the 2 groups and the restenosis rate was similar at 6 months. The prolonged cumulative occlusion time achieved with sequential balloon inflations using a routine balloon catheter improves the immediate results of PTCA. Repeat catheterization shows no effect of prolonged sequential inflations on the restenosis rate.

Aged↗
PubMed1996

Affinity maturation of a high-affinity human monoclonal antibody against the third hypervariable loop of human immunodeficiency virus: use of phage display to improve affinity and broaden strain reactivity.

The present study set out to investigate whether phage display could be used to improve the properties of a high-affinity human monoclonal antibody directed against the third hypervariable loop (V3 loop) of human immunodeficiency virus (HIV). The aim was to increase affinity through slowing the dissociation rate (off-rate constant of koff), whilst retaining the ability of this antibody to bind diverse V3 loop sequences. When reformatted as a scFv, the antibody fragment retained the properties of the parental IgG, including the ability to neutralise virus. Heavy and light chains were sequentially replaced with repertoires of variable domains from non-immunised human donors followed by selection on biotinylated synthetic peptide. All selected variants derived from the same germline as the parental antibody. Variants of the light chain provided little if any improvement, whereas two residue changes in VHCDR2 and one in VHFR3 resulted in a reduced koff from gp120 protein of the MN strain (MNgp120) and synthetic V3 loop peptides as measured by surface plasmon resonance using the BIAcore instrument (Pharmacia Biosensor). VHCDR3 was modified using synthetic oligonucleotides and several clones with reduced koff identified, a number of different substitutions occurring at a single residue position. The residues in the heavy chain identified as reducing koff were simultaneously randomised by site-directed mutagenesis, resulting in scFv variants with koff slowed up to sevenfold. Far from compromising recognition of variant loops, binding to these sequences was improved; the koff from synthetic peptides modelled on V3 loop variants being slowed to a degree similar to that observed with MNgp120. All four changes were located towards either extremes of CDRs 2 and 3, suggesting that the mechanism of improvement may be one of alternation of loop conformation. This work illustrates that phage display can be used to tailor the properties of a therapeutic monoclonal antibody in a predefined fashion.

Amino Acid Sequence↗
PubMed1996

The squalestatins: decarboxy and 4-deoxy analogues as potent squalene synthase inhibitors.

Squalestatins without either the hydroxy group at C-4 or the carboxylic acid at C-3 or C-4 were prepared and evaluated for their ability to inhibit rat liver microsomal squalene synthase (SQS) in vitro. These modifications were well tolerated for compounds with the 4,6-dimethyloctenoate ester at C-6 (S1 series). However in analogues without the C-6 ester (H1 series), removal of the C-4 hydroxy group gave compounds with reduced potency, whereas decarboxylation at C-3 resulted in a dramatic loss of SQS inhibitory activity. In comparison with S1 1, C-4 deoxyS1 3 and C-3 decarboxyS1 10 have shorter in vivo durations of action on the inhibition of hepatic cholesterol biosynthesis in rats. C-4 deoxyS1 3 retains good serum cholesterol-lowering ability in marmosets, while C-3 decarboxyS1 10 showed only a marginal effect even at high dose.

Animals↗
PubMed1996

Distal splenorenal shunt versus 10-mm low-diameter mesocaval shunt for variceal hemorrhage.

BACKGROUND: Portal hypertension surgery remains a good therapeutic choice for well selected patients with variceal bleeding. The distal splenorenal shunt (DSRS) has shown good long-term results and low-diameter shunts have emerged as an alternate choice. METHODS: A prospective, controlled and not randomized study was designed to compare the DSRS (23 patients) and the low-diameter 10 mm ring reinforced PTFE mesocaval shunt (LDMCS) (22 patients) in low-risk electively operated patients (Child-Pugh A-B). The operation was selected according to the anatomical status of the veins. RESULTS: Both groups were comparable. No differences were observed regarding rebleeding, operative mortality and survival. Significative differences were observed regarding encephalopathy and shunt thrombosis (higher in the LDMCS). Postoperative angiography showed better maintenance of portal blood flow in the DSRS group. CONCLUSIONS: Both operations are adequate alternatives for the elective treatment of portal hypertension in low-risk patients. However, the DSRS has more advantages than the LDMCS.

Adult↗
PubMed1996

Intracellular location of the Saccharomyces cerevisiae CDC6 gene product.

The CDC6 gene product from Saccharomyces cerevisiae is required for transition from late G1 to S phase of the cell cycle. We have investigated the subcellular localization of the CDC6 protein in yeast to explore where Cdc6p exerts its gene function (s). Using affinity-purified sera we localized Cdc6p to the cytoplasm and the nuclear matrix by both subcellular fractionation and indirect immunofluorescence microscopy. The nuclear localization was confirmed to be in the nuclear scaffold by the low-salt extraction method. The Cdc6p cannot be detected in the mitochondrial or plasma membrane fractions. Using indirect immunofluorescence, we found that a subpopulation of Cdc6p migrated into the nucleus after G1/S transition and diminished after M phase, suggesting its temporal role in nuclear DNA replication. The predicted Cdc6p polypeptide contains a conserved nuclear localization, 27PLKRKKL33, similar to that of the SV40 large T antigen and other nuclear proteins. To test whether this peptide segment plays a role in mediating nuclear transport, we have carried out site-directed mutagenesis to alter the conserved 29Lys to Thr and Arg. The wild-type nuclear localization signal of Cdc6p was found to mediate the LacZ reporter gene fused to CDC6 efficiently to the nucleus, but not the mutated versions of the nuclear localization motif. The results suggested that 29Lys is important in mediating nuclear localization, the 29Thr and 29Arg mutant versions of the CDC6 gene were also unable to complement the cdc6 temperature-sensitive mutant. However, when these mutants were expressed from a multicopy plasmid, the mutated genes could complement the mutation. Similar results were obtained in the cdc6-disrupted cells. Taken together, we suggest that (i) Cdc6p is predominantly located in the cytoplasm, (ii) the nuclear entry of Cdc6p is cell cycle dependent, and (iii) nuclear entry of Cdc6p is mediated by its nuclear localization signal. The presence of Cdc6p in both the nucleus and the cytoplasm suggests a model that Cdc6p exerts its gene function in DNA replication and mitotic restraint in the cell cycle.

Amino Acid Sequence↗
PubMed1996

Factors that enhance continued trauma center participation in trauma systems.

OBJECTIVES: To examine hospital, trauma system, and reimbursement factors that offset the financial burdens of trauma care delivery and to assess how proposed Medicaid and Medicare budget cuts may affect the ability of hospitals to alleviate financial pressures related to trauma care delivery. DESIGN AND SETTING: In-depth interviews and data collection for trauma centers in 12 metropolitan areas with populations of 1 million or more. PARTICIPANTS: Seventy trauma centers in these large urban communities that indicated a continuing commitment to providing trauma services for the foreseeable future. MAIN OUTCOME MEASURES: Hospital, trauma system, and reimbursement characteristics that distinguish hospitals that are better able to alleviate the financial burdens of indigent trauma care and a financial analysis that assesses payment adequacy for different payers and overall financial outcomes. DATA SOURCES: Data from a variety of sources were obtained to measure the factors that affect the operation and financing of trauma centers: published and unpublished hospital data from the American Hospital Association; trauma center level, length of operation, and the availability of alternative centers from a recently published study; Health Care Financing Administration data on Medicare and Medicaid program characteristics; automobile insurance requirements; and patient discharge data. Most data are reflective of 1992. RESULTS: Public hospitals, teaching hospitals, and institutions receiving supplemental indigent care payments appear to be best able to mitigate the financial burdens of uncompensated trauma care, especially those with moderate indigent care loads. A detailed financial analysis found that private hospitals with trauma centers were near break-even in 1992 for trauma care delivery and public hospitals experienced financial losses. Proposals to reduce Medicaid and Medicare would create substantial reductions in hospital payments for hospital-wide patient care and trauma patients specifically. CONCLUSION: Proposed Medicaid and Medicare payment cuts are likely to eliminate the delicate financial balance that many urban hospitals have achieved in providing trauma care. The erosion in funding from public programs may portend a new wave of trauma center closures as hospitals seek to deal with reduced reimbursement by eliminating unprofitable services.

Diagnosis-Related Groups↗
PubMed1996

Sporadic Leber hereditary optic neuropathy in Australia and New Zealand.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is one of the more common forms of hereditary optic neuropathy and one of the few mitochondrial neuropathies. Prior to the advent of molecular DNA testing, the diagnosis depended on the recognition of typical fundal changes, as well as a family history of maternal transmission. Sporadic cases were therefore diagnosed with a level of uncertainty. The aim of this study is to identify the proportion of patients with idiopathic bilateral optic neuropathy/atrophy who are suffering from LHON. METHODS: Requests were sent to all ophthalmologists and neurologist in Australia and New Zealand for blood or hair follicle samples of patients with diagnosis of bilateral optic neuropathy/atrophy of uncertain aetiology for DNA testing by restriction endonuclease analysis. RESULTS: One hundred and forty-four samples were received, of which 96 were sporadic cases of idiopathic optic atrophy. Eleven of these sporadic patients were found to harbour pathogenetic mitochondrial point mutations associated with LHON. CONCLUSIONS: Our results indicated that 11% of patients with bilateral optic neuropathy/atrophy of uncertain aetiology are suffering from LHON. Comparing this data with all the known familial cases of LHON, we report that at least 8% of all LHON cases in Australia are sporadic. We concluded that mtDNA testing for LHON in patients with idiopathic optic atrophy should be included in the initial laboratory work-up.

Australia↗
PubMed1996

Endoscopic management of cerebrospinal fluid fistulae and traumatic cephalocoele.

The excellent visualisation and atraumatic surgical techniques of endoscopic sinus surgery were applied to the management of 5 patients with cerebrospinal fluid (CSF) fistulae in the anterior skull base. The CSF fistula was iatrogenic in three patients, post-traumatic in one patient and primary in another patient. The role of endoscopes in the diagnosis and management of CSF rhinorrhoea is discussed. These five case reports illustrate the use of rigid transnasal endoscopy for diagnosis and management of CSF fistulae. The use of endoscopes allowed us to accurately localise and repair CSF fistulae. Our technique and results of endoscopic management of CSF fistulae are discussed. Using the endoscopic transnasal approach and minimally invasive techniques the fistulae were successfully repaired in all 5 patients.

Adult↗