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Biomedical subjects

R Chan

Publications and source records attributed to R Chan.

At least 19 recordsLinked to original sources
PubMed2006

Identification of penumbra and infarct in acute ischemic stroke using computed tomography perfusion-derived blood flow and blood volume measurements.

BACKGROUND AND PURPOSE: We investigated whether computed tomography (CT) perfusion-derived cerebral blood flow (CBF) and cerebral blood volume (CBV) could be used to differentiate between penumbra and infarcted gray matter in a limited, exploratory sample of acute stroke patients. METHODS: Thirty patients underwent a noncontrast CT (NCCT), CT angiography (CTA), and CT perfusion (CTP) scan within 7 hours of stroke onset, NCCT and CTA at 24 hours, and NCCT at 5 to 7 days. Twenty-five patients met the criteria for inclusion and were subsequently divided into 2 groups: those with recanalization at 24 hours (n=16) and those without (n=9). Penumbra was operationally defined as tissue with an admission CBF <25 mL x 100 g(-1) x min(-1) that was not infarcted on the 5- to 7-day NCCT. Logistic regression was applied to differentiate between infarct and penumbra data points. RESULTS: For recanalized patients, CBF was significantly lower (P<0.05) for infarct (13.3+/-3.75 mL x 100 g(-1) x min(-1)) than penumbra (25.0+/-3.82 mL x 100 g(-1) x min(-1)). CBV in the penumbra (2.15+/-0.43 mL x 100 g(-1)) was significantly higher than contralateral (1.78+/-0.30 mL x 100 g(-1)) and infarcted tissue (1.12+/-0.37 mL x 100 g(-1)). Logistic regression using an interaction term (CBFxCBV) resulted in sensitivity, specificity, and accuracy of 97.0%, 97.2%, and 97.1%, respectively. The interaction term resulted in a significantly better (P<0.05) fit than CBF or CBV alone, suggesting that the CBV threshold for infarction varies with CBF. For patients without recanalization, CBF and CBV for infarcted regions were 15.1+/-5.67 mL x 100 g(-1) x min(-1) and 1.17+/-0.41 mL x 100 g(-1), respectively. CONCLUSIONS: We have shown in a limited sample of patients that CBF and CBV obtained from CTP can be sensitive and specific for infarction and should be investigated further in a prospective trial to assess their utility for differentiating between infarct and penumbra.

Acute Disease↗
PubMed2006

Endostatin therapy reveals a U-shaped curve for antitumor activity.

Developing continuous systemic delivery of endostatin has been a goal of many laboratories. We have employed a method of gene therapy utilizing different viral constructs. Here, we report that a new serotype of adeno-associated viruses, which incorporates canine endostatin, provides dose-dependent transgene expression in the circulation after intramuscular injection in mice. Elevated levels of endostatin remained stable in the circulation for at least 4 months. In vitro assays determined that the protein expressed was biologically active. Antitumor activities of the above construct demonstrated a U-shape curve, where the maximum activity was observed within a certain critical concentration range. These data suggest that an optimum dose range may be required to achieve therapeutic efficacy in large animal models.

Amino Acid Sequence↗
PubMed2005

Preliminary studies of biochemical changes (ethoxycoumarin O-deethylase activities and vitellogenin induction) in two species of shrimp (Farfantepenaeus duorarum and Litopenaeus setiferus) from the Gulf of Mexico.

Several investigations have demonstrated that the increase in chemicals in the environment may have caused effects on aquatic life and wildlife. The impact from oil production activities on the benthic community structure and shrimp (Farfantepenaeus duorarum and Litopenaeus setiferus) biochemical markers were studied in the Gulf of Mexico, which is heavily contaminated by polycyclic aromatic hydrocarbons and heavy metals. Shrimp were collected from a control area and from an area close to oil production platforms during October and November 2002. There was no spatial difference in exposure and response probably because shrimp migrate, as results did not show significant differences in cytochrome P4501A (as measured by ethoxycoumarin O-deethylase (ECOD) metabolism) between the two sites. In October, shrimp ECOD activities were higher and statistically different from those measured in the samples taken in November. As for ECOD activities, with the concentration of vitellogenin as another biomarker, there were no differences between the shrimp collected from the control area and the shrimp collected on the oil production platforms. In this case the concentrations were higher in shrimp collected in November vs. shrimp collected in October. However, there are significant correlations between contaminants and responses (biomarkers), indicating an effect of pollution. One of the most important considerations brought up by this kind of study is that, although the majority of groups studying the effects of endocrine disruption have focused almost exclusively on human health or vertebrate wildlife-related issues, it is necessary to increase research focused on understanding the function of hormones in invertebrate species exposed in the field to different kinds of pollutants.

7-Alkoxycoumarin O-Dealkylase↗
PubMed2005

Use of polymerase chain reaction on pooled cervical swabs to detect Chlamydia trachomatis infections in female sex workers in Singapore.

INTRODUCTION: Infections caused by Chlamydia trachomatis (C. trachomatis) is one of the commonest sexually transmitted infections (STI). As there is currently no laboratory in Singapore that offers the chlamydia culture tests, alternative laboratory methods were developed and antigen detection methods such as enzyme immunoassays (EIA) proved to be even less sensitive than cell culture. This study was done to assess the accuracy and sensitivity of pooling five endocervical swabs collected for C. trachomatis testing by polymerase chain reaction (PCR) technology, as compared to the currently used EIA on individual swabs, in female sex workers who were seen at a STI clinic in Singapore. METHODS: A total of 1,182 endocervical swab specimens were analysed by EIA as well as in pools of five specimens using PCR. Any pool with a positive PCR result for C. trachomatis infections was subjected to repeat PCR testing of the five individual specimens in the pool. RESULTS: There were a total of 48 confirmed cases of C. trachomatis infection. EIA detected 19 positive samples for C. trachomatis, yielding a prevalence of 1.6 percent among the sex workers tested. Pooled PCR testing showed a higher prevalence rate of 4.1 percent, with 48 PCR positive samples. All cases that were EIA positive were also PCR positive. Individual runs on 200 random samples as well as on 220 individual samples from positive pooled results showed PCR inhibition rates ranging from 1.5 percent to 2.3 percent. However, the PCR inhibition rate was 0 percent with the use of pooling. Sensitivity of EIA was 39.6 percent, with 100 percent specificity. EIA tests had a false negative rate of 60.4 percent. PCR was found to be 100 percent sensitive and specific. CONCLUSION: C. trachomatis infections among female sex workers attending the clinic were found to be higher using PCR technology. Less sensitive methods such as EIA result in undertreatment of otherwise undetected cases. The pooling strategy using pool sizes of five specimens, with a disease prevalence of 4.1 percent is reliable and cost-effective, and has since been introduced in the current medical surveillance scheme for sex workers in the clinic.

Cervix Uteri↗
PubMed2005

Child behaviour and parenting stress in Hong Kong families.

OBJECTIVES: To examine parent perception of child behaviour problems and parenting stress in Hong Kong, and to assess the extent to which they are related to socio-demographic factors and the availability of social support. DESIGN: Cross-sectional survey by using a questionnaire. SETTING: Maternal and Child Health Centres, Hong Kong. PARTICIPANTS: Parents of children aged 4 years who were registered with Maternal and Child Health Centres and were living in Hong Kong between September 2002 and February 2003. MAIN OUTCOME MEASURES: Child behaviour problems and parenting stress. RESULTS: A total of 1009 questionnaires were returned giving a participation rate of 67.0%. About one tenth of parents were experiencing difficulties with their children's behaviour. Parenting stress and children's behaviour problems were associated with presence or absence of social support. Parenting stress was also associated with household income. CONCLUSIONS: The prevalence of child behaviour problems in Hong Kong is comparable with international figures. Intervention programmes should be targeted at parents who experience difficulties with their children's behaviour and parenting.

Chi-Square Distribution↗
PubMed2004

Similarities of omega gliadins from Triticum urartu to those encoded on chromosome 1A of hexaploid wheat and evidence for their post-translational processing.

The omega-gliadins encoded on chromosome 1 of the A genome were purified from Triticum aestivum L. (2n=6 x=42, AABBDD) cv. Butte86, nullisomic 1D-tetrasomic 1A of cv. Chinese Spring (CS N1DT1A), and the diploid T. urartu (2n=2 x=14, AA ). Reverse-phase high-performance liquid chromatography combined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis of gliadin extracts from CS nullisomic-tetrasomic (NT) lines confirmed the assignment to chromosome 1A. The purified omega-gliadins were characterized by mass spectrometry and N-terminal sequencing. The 1A-encoded omega-gliadins were smaller than 1B- or 1D-encoded omega-gliadins. The N-terminal amino acid sequences for 1A omega-gliadin mature peptides were nearly identical to those for the T. urartu omega-gliadins and were more similar to 1D omega-gliadin sequences than to sequences for T. monococum omega-gliadins, barley C-hordeins, or rye omega-secalins. They diverged greatly from the N-terminal sequences for the 1B omega-gliadins. The data suggest that T. urartu is the A-genome donor, and that post-translational cleavage by an asparaginyl endoprotease produces those omega-gliadins with N-terminal sequences beginning with KEL.

Amino Acid Sequence↗
PubMed2004

Quantitative analysis of membrane fouling by protein mixtures using MALDI-MS.

Binary aqueous solutions of bovine serum albumin (BSA) and beta-lactoglobulin (bLG) were subject to flux-stepping and constant flux ultrafiltration to identify the apparent critical flux and to study the mechanisms and factors affecting fouling when the membrane is permeable to one protein component. Membranes from these filtration experiments were analyzed using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) to locate and quantify levels of fouling below and above the apparent critical flux. Hydrophilic (PLTK) regenerated cellulose and hydrophobic (PBTK) polysulfone asymmetric membranes were used, both of 30 kDa nominal molecular weight cut-off. For the hydrophilic PLTK membrane, protein deposition was shown to depend on electrostatic forces, exhibiting little or no fouling when the proteins had the same charge sign as that of the membrane. This was found to apply for both dilute equal mass-per-unit-volume and equimolar binary mixtures. For the PBTK membrane, hydrophobic protein-membrane attractive forces were sufficiently strong to cause deposition of bLG even in the presence of repulsive electrostatic forces. For the PBTK membrane deposition exceeded monolayer coverage below and above apparent critical flux conditions but for the PLTK membrane this generally occurred when the apparent critical flux was exceeded. MALDI-MS was shown to be a facile direct analytical technique for individually quantifying adsorbed proteins on membrane surfaces at levels as low as 50 fmol/mm(2). The high levels of compound specificity inherent to mass spectrometry make this approach especially suited to the quantification of individual components in mixed deposits. In this study, MALDI-MS was found to be successful in identifying and quantifying the protein species responsible for fouling.

Complex Mixtures↗
PubMed2004

A case of probable codeine poisoning in a young infant after the use of a proprietary cough and cold medicine.

We report a case of probable poisoning with codeine phosphate in a 3-month-old infant, which was associated with excessive dosing and concomitant use of antihistamines. Investigation into the patient's drug history identified the recent use of a proprietary cough and cold medicine containing codeine phosphate and dexchlorpheniramine. The prescribing information, available from a popular prescribing handbook, listed only one dosage for children, without any adjustment for age or size, and did not bear any warning for its use in young children. A review of the handbook identified seven additional remedies that were similarly listed. Medical practitioners and pharmacists should be aware of this prescribing pitfall. Improvements are needed in the prescribing information pertaining to the use of cough and cold formulas containing opioid or opioid-like antitussives among young children, and clear warnings should be included in drug inserts and formularies.

Antitussive Agents↗
PubMed2003

Synthesis, pharmacology and pharmacokinetics of 3-(4-aryl-piperazin-1-ylalkyl)-uracils as uroselective alpha1A-antagonists.

Predominance in the urethra and prostate of the alpha(1A)-adrenoceptor subtype, which is believed to be the receptor mediating noradrenaline induced smooth muscle contraction in these tissues, led to the preparation of alpha(1A)-selective antagonists to be tested as uroselective compounds for the treatment of benign prostatic hyperplasia. Thus, a number of selective alpha(1A)-adrenoceptor antagonists were synthesized and assayed in vitro for potency and selectivity. Dog pharmacokinetic parameters of 12 (RO700004) and its metabolite 40 (RO1104253) were established. The relative selectivity of intravenously administered 12, 40 and standard prazosin to inhibit hypogastric nerve stimulation-induced increases in intraurethral prostatic pressure versus phenylephrine-induced increases in diastolic blood pressure in anesthetized dogs was 76, 71 and 0.6, respectively.

Administration, Oral↗
PubMed2003

Resolution of vulvitis circumscripta plasmacellularis with topical imiquimod: two case reports.

Vulvitis circumscripta plasmacellularis (VCP) is a rare but well-described entity. It is notorious for its recalcitrant nature to various modalities of treatment. Intralesional interferon-alpha showed some promise, with complete resolution, but is coupled with the side-effect of myelosuppression. Topical imiquimod is a novel immune response modifier with the ability to induce the production of interferon-alpha. In this paper, we report two cases of VCP whose lesions were resistant to antibiotics, topical and oral corticosteroids, but resolved after a treatment trial with imiquimod.

Adjuvants, Immunologic↗
PubMed2002

The role of angiostatin in the spontaneous bone and prostate cancers of pet dogs.

Angiostatin is a potent inhibitor of angiogenesis generated in cancer-bearing hosts by tumor-derived proteases. Because the naturally occurring bone and prostate cancers of pet dogs provide unique model systems to study factors that regulate cancer progression and tumor dormancy, we investigated the capacity of these tumors to generate angiostatin. We determined that angiostatin fragments are present in urine of dogs with bone cancer. The identity of these fragments was confirmed by comparison of the experimentally determined protein sequence to that of a clone of canine angiostatin. Importantly, these fragments were absent in urine collected from the same dogs after complete surgical removal of the primary tumor. We also demonstrate that canine prostate cancer cells are capable of processing plasminogen to angiostatin in vitro. These findings provide rationale for using spontaneous canine tumor models to isolate endogenous angiogenesis inhibitors and to investigate their therapeutic use against cancer.

Angiostatins↗
PubMed2002

Why is smoking a risk factor for sudden infant death syndrome?

Smoking is a major risk factor for both Sudden Infant Death Syndrome (SIDS) and respiratory tract infections. Such infections, both viral and bacterial, also increase the SIDS risk. This study investigated the effect of cigarette smoke at two stages of infection: 1) mucosal surface colonization; 2) induction and control of inflammatory responses. For colonization, RSV or influenza A infected cells bound several bacterial species in significantly higher numbers due to increased expression of host cell antigens. Buccal epithelial cells from smokers bound significantly more bacteria. For Staphylococcus aureus, this was associated with increased tar levels. Some SIDS deaths have been proposed to result from high levels of pro-inflammatory mediators elicited by infection and/or cigarette smoke during a developmental period when infants are less able to control inflammatory responses. Inflammatory reponses were compared between blood samples from smokers (n = 42) and non-smokers (n = 60) stimulated with TSST-1 or LPS. Non-smokers had significantly higher IL-6 (P = 0.011), IFN (P = 0.003) and IL-10 (P = 0.000) baseline levels. Non-smokers had higher IFN (P = 0.008) and IL-1 (P = 0.001, 0.007) responses to LPS and higher IL-10 responses to TSST-1 (P < 0.05) and LPS (P < 0.000). This study highlights that smoking increases the SIDS risk by greater susceptibility to viral and bacterial infections and enhanced bacterial binding after passive coating of mucosal surfaces with smoke components. In animal models, IL-10 reduced the lethal effect of staphylococcal toxins. In this study, smokers had lower IL-10 responses toTSST-1 and LPS. Dose response effects of cigarette smoke exposure needs to be established in relation to inflammatory response control and infantile infections.

Case-Control Studies↗
PubMed2002

A new top-loading venous bag provides vacuum-assisted venous drainage.

A new venous bag has been developed, prototyped, and tested. The new bag has its inlet, outlet purge, and infusion tubes extending upward from the top of the bag, and are threaded through, bonded to, and sealed within a flat rigid top plate. This design allows the bag to be hung from its top plate by its tubes. It also allows the bag to be: 1) dropped into or removed from its holder, as is done with existing hard-shell reservoirs so that its weight pulls it into the holder without the need for eyelets and hooks and 2) placed closer to the floor so that gravity drainage is facilitated. The V-Bag (VB) is easily sealed within an accompanying rigid housing. Once sealed, vacuum applied to the housing is transmitted across the flexible walls of the bag to the venous blood. Thus, vacuum-assisted venous drainage (VAVD) is obtained as it is with a hard-shell reservoir, but without any contact of air with the blood. Bench tests, using a circuit that simulated the venous side of the cardiopulmonary bypass (CPB) circuit, showed that applying suction to the housing increased venous flow, and the fractional increase in flow was not a function of the venous cannula, but of the level of vacuum applied. In the gravity drainage mode, the bubble counts at the outlet of the V-Bag compared to two other bags were lower at any pumping condition. When used in the VAVD mode, bubble counts were two orders of magnitude lower than when using kinetically assisted venous drainage (KAVD) with a centrifugal pump. Results obtained with the VB suggest its clinical usefulness.

Cardiopulmonary Bypass↗
PubMed2001

The anti-anginal drug fendiline increases intracellular Ca(2+) levels in MG63 human osteosarcoma cells.

The effect of fendiline, an anti-anginal drug, on cytosolic free Ca(2+) levels ([Ca(2+)](i)) in MG63 human osteosarcoma cells was explored by using fura-2 as a Ca(2+) indicator. Fendiline at concentrations between 1 and 200 microM increased [Ca(2+)](i) in a concentration-dependent manner and the signal saturated at 100 microM. The Ca(2+) signal was inhibited by 65+/-5% by Ca(2+) removal and by 38+/-5% by 10 microM nifedipine, but was unchanged by 10 microM La(3+) or verapamil. In Ca(2+)-free medium, pre-treatment with 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) to deplete the endoplasmic reticulum Ca(2+) store inhibited fendiline-induced intracellular Ca(2+) release. The Ca(2+) release induced by 50 microM fendiline appeared to be independent of IP(3) because the [Ca(2+)](i) increase was unaltered by inhibiting phospholipase C with 2 microM U73122. Collectively, the results suggest that in MG63 cells fendiline caused an increase in [Ca(2+)](i) by inducing Ca(2+) influx and Ca(2+) release in an IP(3)-independent manner.

Calcium↗