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Biomedical subjects

T Chan

Publications and source records attributed to T Chan.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of the pro-inflammatory potential of monocytes from healthy adults and those with peripheral arterial disease using an in vitro culture model.

We adapted a monocyte:endothelial cell co-culture model to investigate the pro-inflammatory potential of monocytes from patients with peripheral arterial disease (PAD). Isolated monocytes were cultured with human umbilical vein endothelial cells (HUVEC) for 24h, after which the ability of the HUVEC to recruit flowing neutrophils was tested. Development of a usable protocol required comparisons of primary HUVEC with cells that had been passaged and/or frozen and thawed, evaluation of optimal culture media and comparison of monocytes from freshly drawn and stored blood. We found, for instance, that expansion of HUVEC was assisted by inclusion of hydrocortisone, but this agent was withdrawn before the test phase because it reduced responses of HUVEC. Using the optimal practical protocol, we found great variation in the ability of monocytes from different donors to cause neutrophil adhesion. Slightly more ( approximately 20%) monocytes from patients with PAD adhered to HUVEC than monocytes from healthy controls, and the monocytes from PAD patients induced approximately 70% greater subsequent adhesion of neutrophils. Thus, we developed a functional model of inflammatory potential usable in clinically-related studies and found that patients with PAD had circulating monocytes with greater than normal ability to activate endothelial cells.

Cells, Cultured↗
PubMed2006

HER-2/neu-gene engineered dendritic cell vaccine stimulates stronger HER-2/neu-specific immune responses compared to DNA vaccination.

HER-2/neu is a candidate for developing breast cancer-targeted immunotherapeutics. Although DNA-based and HER-2/neu transgene-modified dendritic cell (DC)-based vaccines are potent at eliciting HER-2/neu-specific antitumor immunity, there has been no side-by-side study comparing them directly. The present study utilizes an in vivo murine tumor model expressing HER-2/neu antigen to compare the efficacy between adenovirus (AdVneu)-transfected dendritic cells (DC(neu)) and plasmid DNA (pcDNAneu) vaccine. Our data showed that DC(neu) upregulated the expression of immunologically important molecules and inflammatory cytokines and partially converted regulatory T (Tr)-cell suppression through interleukin-6 (IL-6) secretion. Vaccination of DC(neu) induced stronger HER-2/neu-specific humoral and cellular immune responses than DNA vaccination, which downregulated HER-2/neu expression and lysed HER-2/neu-positive tumor cells in vitro, respectively. In two HER-2/neu-expressing tumor models, DC(neu) completely protected mice from tumor cell challenge compared to partial or no protection observed in DNA-immunized mice. In addition, DC(neu) significantly delayed breast cancer development in transgenic mice in comparison to DNA vaccine (P<0.05). Taken together, we have demonstrated that HER-2/neu-gene-modified DC vaccine is more potent than DNA vaccine in both protective and preventive animal tumor models. Therefore, DCs genetically engineered to express tumor antigens such as HER-2/neu represent a new direction in DC vaccine of breast cancer.

Adenoviridae↗
PubMed2005

Concentration and chemical characteristics of PM2.5 in Beijing, China: 2001-2002.

Weekly PM2.5 samples were simultaneously collected at a semi-residential (Tsinghua University) and a downtown (Chegongzhuang) site in Beijing from August 2001 through September 2002. The ambient mass concentration and chemical composition of PM2.5 were determined. Analyses including elemental composition, water-soluble ions, and organic and elemental carbon were performed. The annual average concentrations of PM2.5 were 96.5 microg m(-3) and 106.9 microg m(-3) at CGZ and HU site, respectively. More than 80% of the PM2.5 mass concentrations were explained by carbonaceous species, secondary particles, crustal matters and trace elements at the two sites. Carbonaceous species were the most abundant components, constituting about 45% and 48% of the total PM2.5 mass concentrations at CGZ and THU site, respectively. SO4(2-), NO3- and NH4+ were three major ions, accounting for 37%, 23% and 20%, respectively, of the total mass of inorganic water-soluble ions.

Air Pollutants↗
PubMed2005

Management of heart failure in primary care after implementation of the National Service Framework for Coronary Heart Disease: a cross-sectional study.

OBJECTIVES: To compare the management of heart failure with the standards set out in the National Service Framework for Coronary Heart Disease. STUDY DESIGN: A cross-sectional study in 26 general practices, with a combined list size of 256,188, that are members of the Kent, Surrey and Sussex Primary Care Research Network. METHODS: Information was extracted on the management of 2129 patients with heart failure, of whom 2097 were aged 45 years and over. RESULTS: The prevalence of heart failure was 8.3 per 1000. Prevalence rates increased with age, from 0.2 per 1000 in people aged under 35 years of age to 125 per 1000 in those aged 85 years and over. Coronary heart disease (present in 47%) was the most common comorbid condition in men with heart failure, whereas hypertension (present in 46%) was the most common condition in women. Recording of cardiovascular risk factors was generally higher in younger patients than in older patients, and in men than in women. Blood pressure (92% of men and 90% of women) and smoking status (84% of men and 77% of women) were generally the best-recorded cardiovascular risk factors. Blood electrolytes were recorded in about 83% of men and 75% of women. Only 17% of men and 11% of women with heart failure had a record of undergoing an echocardiogram. Use of angiotensin-converting enzyme (ACE) inhibitors or antagonists was 76% in men with heart failure and 68% in women; lowest rates were seen in older patients. Uptake of influenza immunization was generally high, at 85% in men and 84% in women. CONCLUSIONS: The use of ACE inhibitors in patients with heart failure was higher than in some previous studies. However, many patients have no documentation in their computerized medical records of having undergone key investigations, such as echocardiography.

Adult↗
PubMed2005

Quality and variability of osteoporosis data in general practice computer records: implications for disease registers.

OBJECTIVE: To determine the extent to which routinely collected general practitioner computer data could be used to create disease registers of patients with osteoporosis, and to report any improvement in data quality since previous studies. STUDY DESIGN: Audit using anonymized data extracted from general practice computer records from across England. METHODS: Morbidity Query Information and Export Syntax (MIQUEST) software was used to extract structured data from the 78 volunteer practices that participated in the study. The data were aggregated and analysed. RESULTS: There were 100-fold differences in the rates of recording of relevant data. Many patients receiving treatment had no diagnostic codes. Data about secondary causes of osteoporosis and fractures were more consistently recorded than data relating to falls. There were no data to indicate whether fractures were low impact. T-scores, the gold-standard measure of bone density, were very infrequently recorded. CONCLUSIONS: Sufficient data about secondary causes of osteoporosis exist, and these could be searched to identify patients at risk. Meanwhile, fracture recoding could be improved, including likely fragility fractures, and T-scores could be added to computer records. A systematic approach is needed to raise the computer records to a standard where they can be used as valid and reliable disease registers.

Accidental Falls↗
PubMed2005

[Experiences and results with the locked compression plate for 603 fractures of the distal radius].

Between January 1999 and December 2003 we have treated 603 patients with a fracture of the distal radius without concomitant injuries with the Synthes locked compression plate. The locked compression plate, the concept of the postoperative treatment, and our results are presented. In most cases we have used the palmar plate. We see an indication for the palmar plate in the A2 and A3, B2 and B3 and in all C fractures. It is also practicable for fractures with dorsal comminutions. Because of its permanent retention due to the subchondral fixation of the splints (internal fixation), this new plate makes early mobilization possible. The palmar approach with its good soft-tissue coverage not only reduces the risk of infections but also offers the possibility of not having to remove the plate. A cancellous bone graft is only seldom necessary.

Adolescent↗
PubMed2005

Consenting to blood: what do patients remember?

We sought to characterize the consent process for transfusion and determine its impact on patients' knowledge and level of comfort with receiving blood. We identified all adult patients who had received blood transfusion at a tertiary care centre over 3 months. Patients who were discharged each received a survey that assessed their (1) recall of the consent process, (2) recall of information conveyed, (3) assessment of the discussion's understandability and (4) perceived knowledge of as well as comfort level with transfusion as a result of the discussion. Overall, 80% of respondents recalled discussing and signing an informed consent. Information was mostly conveyed by attending physicians (35%) and consent obtained in the patient's hospital room (38%) or the preadmission clinic (19%). Although the majority recalled the consent process, many did not recall the discussion of specific transfusion risks or alternatives to donor blood (88%). Although the majority felt the discussion was at least somewhat understandable (77%), only 35% felt better informed and more comfortable with accepting blood. Despite implementation of written informed consent for transfusion, patients' recollection and understanding of risks and alternatives remain poor. This suggests the need for improving risk communication.

Adolescent↗
PubMed2004

Extending low-dose epidural analgesia for emergency Caesarean section using ropivacaine 0.75%.

We compared ropivacaine 0.75% and bupivacaine 0.5% for extending low-dose epidural analgesia for emergency Caesarean section, using a prospective double-blind randomised controlled trial design. The trial was halted after 45 patients were studied (23 ropivacaine; 22 bupivacaine) because bupivacaine was replaced by levobupivacaine in our unit. Time to reach T4 for loss of cold sensation was similar in both groups, although analgesic supplementation was required less often in the ropivacaine group than in the bupivacaine group (2/23 vs. 9/21; p = 0.01).

Adult↗
PubMed2003

Nissen fundoplication has a vagolytic effect on the lower esophageal sphincter.

BACKGROUND: Laparoscopic Nissen fundoplication is an increasingly utilized option for the treatment of gastroesophageal reflux disease (GERD). However, many questions remain as to the mechanism by which this operation prevents GERD in those without hiatal hernias or incompetent lower esophageal sphincters (LES). It is known that these patients experience reflux due to excess transient lower esophageal sphincter relaxations (TLESR), inappropriate and short-lived relaxation of the LES and crural diaphragm. The purpose of this study was to determine if Nissen fundoplication affects the neural pathways involved in the TLESR reflex. METHODS: Five dogs were anesthetized and intubated. Both vagal nerves and the right phrenic nerve were isolated. A continuous water perfusion manometric catheter was situated at the LES. The nerves were then electrically stimulated and the resultant pressure at the LES measured at baseline, and during and after an open Nissen fundoplication. RESULTS: The mean LES pressures before dissection, after esophago-gastric mobilization, and after fundoplication were 47 +/- 13 mmHg, 21 +/- 9 mmHg, and 14 +/- 4 mmHg, respectively. All differences were significant. There was no change noted in LES pressure with stimulation of either or both of the phrenic nerves without concomitant vagal stimulation. CONCLUSION: Nissen fundoplication may prevent GERD in those without a hiatal hernia or incompetent LES by disrupting the efferent vagal fibers to the LES. Such fibers mediate TLESR which are responsible for GERD in these patients.

Animals↗
PubMed2003

Can patients with osteoporosis, who should benefit from implementation of the national service framework for older people, be identified from general practice computer records? A pilot study that illustrates the variability of computerized medical records and problems with searching them.

Although UK general practice is highly computerized, comprehensive use of these computers is often limited to registration data and the issue of repeat prescriptions. The recording of diagnostic data is patchy. This study examines whether patients with, or at risk of, osteoporosis can be readily identified from general practice computer records. It reports the findings of a pilot study designed to show the variability of recording the diagnosis of osteoporosis and osteopenia, as well as how useful surrogate markers might be to identify these patients. The study also illustrates the difficulties that even skilled practitioners in a primary care research network experience in extracting clinical data from practice information systems. Computer searches were carried out across six practices in a general practice research network in the south-east of England. Two of these practices had previously undertaken research projects in osteoporosis and were consequently expected to have excellent data quality in osteoporosis. These two practices had a combined list size of 27,500 and the remaining practices had a combined practice population of 43,000 patients. The data were found to be variable with over 10-fold differences between practices in the recorded prevalence of osteoporosis diagnosis as well as its surrogate markers-such as fragility fractures, long-term steroid prescription, etc. There was no difference in data quality between the two practices that had conducted osteoporosis research and the rest of the group, other than in the areas of diagnostic recording and prescribing for osteoporosis and recording of fractures. Issues were raised by the practices that struggled to identify patients at risk of osteoporosis about the limitations of Read classification in this disease area. Practices need further assistance if the patients at risk are to be identified. Without urgent action, it will be difficult for practices to identify the patients who are likely to benefit from Standard 6-'Falls' of the National Service Framework for Older People. These findings also have broader implications as UK general practice moves towards the implementation of a quality-based contract.

Aged↗
PubMed2002

Recognition of incomplete patterns by bumble bees.

Bumble bees were trained to discriminate between two visual patterns, one of which was rewarding (S+) and one of which was unrewarding (S-). Subsequently, they were tested for discrimination between two non-rewarding patterns: the top halves of the training patterns, the bottom halves or the side halves. Three conditions were tested: (1) When the S+ was a star and the S- was a circle, all halves of the star were chosen above chance level, which may reflect an unlearned preference for radial patterns. (2) When the S+ and S- were reversed, the bottom half and the side half of the circle were chosen above chance level, but not the top half. (3) In the last condition, the S+ was again a circle, but the feeder tube was placed below the training pattern rather than above, and again the bottom halves were discriminated but neither the top nor the side halves were. In learning pattern discriminations, the ventral portion of the pattern is weighted more strongly than the dorsal portion, which enables recognition of incomplete patterns, and the weighting depends little on angle of approach.

Journal Article↗
PubMed2002

The cost effectiveness of dual phase 201Tl thyroid scan in detecting thyroid cancer for evaluating thyroid nodules with equivocal fine-needle aspiration results: the preliminary Taiwanese experience.

The purposes of this study were to assess the helpfulness of dual phase 201Tl thyroid scan for differentiating malignant from benign thyroid lesions in cases of thyroid nodules with equivocal fine-needle aspiration (FNA) biopsy results. In addition, for thyroid nodules with equivocal FNA biopsy results, we try to make a decision analysis model compared the FNA biopsy alone strategy (strategy A) with decision strategy for the assistance of dual phase 201Tl thyroid scan (strategy B) before diagnostic thyroidectomy as thyroid cancer evaluation strategies for hypothetical cohorts of estimated 17,280-29,160 Taiwanese patients/per year with equivocal FNA biopsy results. Based on the findings of surgical histopathology, dual phase 201Tl thyroid scan sensitivity, specificity, and accuracy were 100%, 90%, and 96%, respectively, in cases of 27 thyroid nodules with equivocal FNA biopsy results. In cost effectiveness analysis, the strategy B showed a cost saving of 16,340,480-27,574,560 US dollars in unnecessary diagnostic thyroidectomy cost. The total cost of strategy B showed a cost saving of 13,932,232-23,520,564 US dollars than that of strategy A. The preliminary data indicate that dual phase 201Tl thyroid scan can save the cost of unnecessary diagnostic thyroidectomy in Taiwanese patients with equivocal FNA biopsy results. In addition, we may provide a noninvasive diagnostic method--dual phase 201Tl thyroid scan, as the first priority for Taiwanese patients with equivocal FNA biopsy before diagnostic thyroidectomy under the coverage of the national health insurance system in Taiwan.

Adolescent↗
PubMed2001

Specific targeting, biodistribution, and lack of immunogenicity of chimeric anti-GD3 monoclonal antibody KM871 in patients with metastatic melanoma: results of a phase I trial.

PURPOSE: KM871 is a chimeric monoclonal antibody against the ganglioside antigen GD3, which is highly expressed on melanoma cells. We conducted an open-label, dose escalation phase I trial of KM871 in patients with metastatic melanoma. PATIENTS AND METHODS: Seventeen patients were entered onto one of five dose levels (1, 5, 10, 20, and 40 mg/m2). Patients received three infusions of KM871 at 2-week intervals, with the first infusion of KM871 trace-labeled with indium-111 (111In) to enable assessment of biodistribution in vivo. Biopsies of metastatic melanoma sites were performed on days 7 to 10. RESULTS: Fifteen of 17 patients completed a cycle of three infusions of KM871. No dose-limiting toxicity was observed during the trial; the maximum-tolerated dose was therefore not reached. Three patients (at the 1-, 5-, and 40-mg/m2 dose levels) developed pain and/or erythema at tumor sites consistent with an inflammatory response. No normal tissue uptake of 111In-KM871 was observed, and tumor uptake of 111In-KM871 was observed in all lesions greater than 1.5 cm (tumor biopsy 111KM871 uptake results: range, 0.001% to 0.026% injected dose/g). The ratio of maximum tumor to normal tissue was 15:1. Pharmacokinetic analysis revealed a 111In-KM871 terminal half-life of 7.68 +/- 2.94 days. One patient had a clinical partial response that lasted 11 months. There was no serologic evidence of human antichimeric antibody in any patient, including one patient who received 16 infusions over a 12-month period. CONCLUSION: This study is the first to demonstrate the biodistribution and specific targeting of an anti-GD3 antibody to metastatic melanoma in patients. The long half-life and lack of immunogenicity of KM871 makes this antibody an attractive potential therapy for patients with metastatic melanoma.

Adult↗
PubMed2001

A mild and general solid-phase method for the synthesis of chiral polyamines. Solution studies on the cleavage of borane-amine intermediates from the reduction of secondary amides.

A mild oxidative workup protocol using iodine in an acetic acid-acetate buffer solution is described for the cleavage of borane-amine adducts arising from the borane-promoted reduction of polyamides supported onto practical trityl-based resins. Chiral polyamines with diverse side-chain functionalities can be generated as free bases without premature release from the solid support and with essentially no racemization using this method. A series of model oligomeric secondary diamides 6 containing various alpha-amino acid residues (Val, Phe, Tyr, Ser, Cys, Met, Gln, Trp) provided triamine products 8 in high yields and good to excellent purity. On the other hand, a substrate containing a tertiary amide (15) formed a rather unusual triaminoborane intermediate that required more stringent workup conditions to liberate the polyamine product 20. The reduction of oligomeric tertiary amides such as 9 was found sluggish, but these compounds could nonetheless be obtained in high purity from in situ reductive amination of the corresponding secondary amines. Control studies, carried out in solution with model secondary amide 23, confirmed the efficiency of the buffered iodine solution and highlighted several advantages (no heating necessary, no need for strong bases or acids) over existing methods for the cleavage of borane-amine adducts. A possible mechanism involving all buffer components (iodine, acetic acid, and acetate ion) is proposed in which borane-amine adducts are transformed first to the monoiodoborane-amine and then to the corresponding acetoxyborane-amine adduct of much weaker coordination affinity. The latter would dissociate readily and get trapped by the acetic acid to provide the desired secondary amine. This reduction/oxidative workup protocol is useful as a general method for the facile solid-phase synthesis of polyamines for eventual release in solution and use in various applications. It is also potentially very useful toward the synthesis and screening of bead-supported libraries of free oligoamines assembled through split-pool methods.

Journal Article↗
PubMed2001

Cytochrome P450 2E1 metabolically activates propargyl alcohol: propiolaldehyde-induced hepatocyte cytotoxicity.

Pargyline, an antihypertensive agent and monoamine oxidase inhibitor, induces hepatic GSH depletion and hepatotoxicity in vivo in rats [E.G. De Master, H.W. Sumner, E. Kaplan, F. N. Shirota, H.T. Nagasawa, Toxicol. Appl. Pharmacol. 65 (1982) 390-401]. Propargyl alcohol (2-propyn-1-ol), because of its structural similarity to allyl alcohol, was thought to be activated by alcohol dehydrogenase. However, it is a poor substrate compared to allyl alcohol and it was therefore proposed that propargyl alcohol-induced liver injury involved metabolic activation by catalase/H(2)O(2) [E.G. De Master, T. Dahlseid, B. Redfern, Chem. Res. Toxicol. 7 (1994) 414-419]. In the following we showed that; (1) propargyl alcohol-induced cytotoxicity was markedly enhanced in CYP 2E1-induced hepatocytes and prevented by various CYP 2E1 inhibitors but was only slightly affected when alcohol dehydrogenase was inhibited with methylpyrazole/DMSO or when catalase was inactivated with azide or aminotriazole, (2) hepatocyte GSH depletion preceded cytotoxicity and was inhibited by cytochrome P450 inhibitors but not by catalase/alcohol dehydrogenase inhibitors. GSH conjugate formation during propargyl alcohol metabolism by microsomal mixed function oxidase in the presence of GSH was also prevented by anti-rat CYP 2E1 or CYP 2E1 inhibitors, (3) cytotoxicity was prevented when lipid peroxidation was inhibited with antioxidants, desferoxamine (ferric chelator) or dithiothreitol. Propargyl alcohol-induced cytotoxicity and reactive oxygen species formation were markedly increased in GSH-depleted hepatocytes. All of this evidence suggests that propargyl alcohol-induced cytotoxicity involves metabolic activation by CYP 2E1 to form propiolaldehyde that causes hepatocyte lysis as a result of GSH depletion and lipid peroxidation.

Aldehydes↗
PubMed2001

Magnetic resonance angiography at 0.3 T using MS-325.

Preliminary results on MS-325 versus ProHance enhanced magnetic resonance angiography (MRA) at low field strength in a rabbit model are reported. MS-325-enhanced images were acquired in vivo and compared with pre-contrast as well as conventional contrast-enhanced images. Visual image quality observations correlated with measurements of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). While published in vitro data show 7-fold greater relaxivity for MS-325 compared with conventional contrast agents, we observed an even greater effect here due, presumably, to better matching of the longer vascular lifetime with longer scan time in this study. In addition, overall vessel clarity improved significantly throughout all the phases of the experiment in MS-325-enhanced images when compared with conventional contrast-enhanced images.

Abdomen↗
PubMed2001

Healing of burn wounds in transgenic mice overexpressing transforming growth factor-beta 1 in the epidermis.

Transforming growth factor-beta (TGF-beta) isoforms are multifunctional cytokines that play an important role in wound healing. Transgenic mice overexpressing TGF-beta in the skin under control of epidermal-specific promoters have provided models to study the effects of increased TGF-beta on epidermal cell growth and cutaneous wound repair. To date, most of these studies used transgenic mice that overexpress active TGF-beta in the skin by modulating the latency-associated-peptide to prevent its association with active TGF-beta. The present study is the first to use transgenic mice that overexpress the natural form of latent TGF-beta 1 in the epidermis, driven by the keratin 14 gene promoter to investigate the effects of locally elevated TGF-beta 1 on the healing of partial-thickness burn wounds made on the back of the mice using a CO(2) laser. Using this model, we demonstrated activation of latent TGF-beta after wounding and determined the phenotypes of burn wound healing. We found that introduction of the latent TGF-beta1 gene into keratinocytes markedly increases the release and activation of TGF-beta after burn injury. Elevated local TGF-beta significantly inhibited wound re-epithelialization in heterozygous (42% closed versus 92% in controls, P < 0.05) and homozygous (25% versus 92%, P < 0.01) animals at day 12 after wounding. Interestingly, expression of type I collagen mRNA and hydroxyproline significantly increased in the wounds of transgenic mice, probably as a result of a paracrine effect of the transgene.

Animals↗