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Biomedical subjects

J Tsang

Publications and source records attributed to J Tsang.

At least 19 recordsLinked to original sources

Computer-assisted detection for CT colonography: external validation.

AIM: To externally validate a computer-assisted detection (CAD) system for computed tomography (CT) colonography, using data from a single centre uninvolved with the software development. MATERIALS AND METHODS: Twenty-five multi-detector CT colonography examinations of patients with validated polyps accumulated at a single centre were examined by two readers who used endoscopic and histopathological data to identify polyp coordinates. A CAD system that had been developed using data from elsewhere, and had not previously encountered the present data, was then applied to the data at sphericity filter settings of 0.75 and 0.50 and identified potential polyps. True-positive, false-negative, and false-positive counts were determined by comparison with the known polyp coordinates. RESULTS: Twenty-five patients had 57 polyps, median size 6mm (range 1-15mm). Per-patient sensitivity for the CAD system was 96% (24 of 25). The CAD system detected 44 (77%) polyps at sphericity setting 0.75 and 49 (86%) polyps at sphericity 0.50: the additional five polyps detected all measured 5mm or less. Sphericity of 0.75 resulted in a median of 10 (one to 34) easily dismissed false-positive prompts per patient and a median of 4 (zero to 15) that needed three-dimensional rendering before dismissal. This rose to 32 (16 to 99) and 11 (three to 35), respectively, at sphericity 0.5. CONCLUSIONS: A per-patient sensitivity of 96% was found for the CAD system (in patients with a median polyp diameter of 6mm) using external validation, a more stringent test than either internal cross-validation or temporal validation. Decreasing sphericity increases sensitivity for small polyps at the expense of decreased specificity.

Colonic Polyps↗

Adoptive cell therapy using in vitro generated human CD4+ CD25+ regulatory t cells with indirect allospecificity to promote donor-specific transplantation tolerance.

The holy grail in clinical transplantation is the establishment of long-term donor-specific transplantation tolerance with the minimum use of immunosuppressive agents. CD4+ CD25+ regulatory T cells (Tregs) play a crucial role in the prevention of autoimmunity, and appear to mediate transplantation tolerance. Harnessing Tregs for potential adoptive cell therapy to promote donor-specific transplantation tolerance is promising. Here we show that human CD4+ CD25+ Tregs with indirect allospecificity for an HLA-A2 (103-120) peptide can be generated from purified peripheral blood CD4+ CD25+ by priming with HLA-DR0101+ A2- autologous dendritic cells (DCs) pulsed with the A2 peptide in vitro. The antigen specificity for the A2 peptide was demonstrated in functional assays and flow cytometric analysis using a fluorescent tetramer composed of HLA-DR0101 and the A2 peptide. The CD4+ CD25+ Tregs with indirect allospecificity for the A2 peptide showed potent suppression of an indirect alloresponse by effector CD4+ CD25- T-helper cells. Importantly, the selected CD4+ CD25+ Tregs can be expanded substantially to meet a therapeutic end after T-cell receptor (TCR) stimulation by CD3/CD28 antibody-coated beads in the presence of high doses of interleukin-2 (IL-2). The expanded CD4+ CD25+ Tregs highly expressed Foxp3, and retained their suppressive properties and maintained expression of lymphoid homing receptor CD62L. Taken together, these data pave the way for clinical studies using in vitro generated and expanded human CD4+ CD25+ Tregs with indirect allospecificity as therapeutic reagents to promote donor-specific transplantation tolerance.

Adoptive Transfer↗

Psychological distress and negative appraisals in survivors of severe acute respiratory syndrome (SARS).

BACKGROUND: Severe acute respiratory syndrome (SARS) is a novel disease. The authors have limited knowledge of its impact on mental health. The present study aimed to examine the level and extent of psychological distress of SARS survivors following 1-month recovery, to explore patients' negative appraisals of the impact of SARS, and to evaluate the associations between psychological distress and negative appraisals. METHOD: The Beck Anxiety Inventory, the Beck Depression Inventory, and a newly developed measure, the SARS Impact Scale (SIS), were mailed to 453 Hong Kong Chinese SARS survivors discharged from hospital for 4 weeks or more. RESULTS: A total of 425 patients received the questionnaires and 180 (mean age 36.9 years; 120 women) gave valid replies. The response rate was 42.4 %. The participants also represented 13.6 % of all adult survivors in Hong Kong. About 35 % of respondents reported 'moderate to severe' or 'severe' ranges of anxiety and/or depressive symptoms. It was found that those working as healthcare workers or having family members killed by SARS were more prone to develop subsequent high levels of distress. Factor analyses extracted three meaningful factors of the SIS, namely 'survival threat', 'physical impact', and 'social impact'. Negative appraisals at the acute phase and 1-month recovery significantly accounted for substantial portions of variances for anxiety and depressive symptoms, after the effects of other psychosocial variables were controlled. CONCLUSIONS: Psychological distress of SARS survivors at 1-month recovery is real and significant. Negative appraisals may play a pivotal role in the development of psychological distress for SARS survivors, at least in the short term.

Adaptation, Psychological↗

Primary follicular lymphoma of the small intestine.

While nodal follicular lymphoma is prevalent in western countries, primary extranodal presentation is rare. We present the clinico-pathological and radiologic features of a patient with primary follicular lymphoma of the small intestine presenting with intestinal obstruction. This is followed by the discussion on the frequency and staging systems for primary gastrointestinal lymphomas, and the relevance of monoclonal anti-CD20 antibody therapy.

Aged↗

Role of the endothelin system in secondary pulmonary hypertension related to air embolism: lessons learned from testing four classes of endothelin blockers in a rat model.

A rat model of acute pulmonary air embolism (APAE) was developed. These animals had a higher right ventricular systolic pressure (RVSP) (+ 69% at 15-minute peak, and 21-34% at 30-180 minutes), as well as a reduced mean arterial blood pressure (10-20% at 60-180 minutes), heart rate (20-26% at 60-180 minutes) and PaO2 (9-11% at 30-180 minutes) compared with control rats. The role of the endothelin (ET) system, known to be involved in pulmonary hypertension of various etiologies, was investigated by evaluating the effect of the four classes of ET blockers: ET-converting enzyme inhibitor (ECEi) (CGS 35066), selective endothelin-A receptor antagonist (ETA-Ra) (Atrasentan, ABT-627), endothelin-B receptor antagonist (ETB-Ra) (A-192621) or mixed endothelin-A/endothelin-B receptor antagonist (ETA/B-Ra) (A-182086) in this animal model. All four were effective, to various degrees, at reducing the APAE-induced rise in RVSP. The relative efficacy of those compounds in reducing the acute elevation (15 minutes) of RVSP was ECEi >or= ETA/B-Ra >> ETA-Ra = ETB-Ra. The sustained elevation (30-180 minutes) of RVSP was totally abolished by ECEi and attenuated by other ET blockers with a relative efficacy of ETA-Ra > ETA/B-Ra >or= ETB-Ra. ET receptor antagonists did not affect right ventricular basal tone (control rats) whereas ECEi reduced it by up to 12% after 2 hours. The APAE reduction in mean arterial blood pressure was unaffected by ETARa, was completely normalized by ETB-Ra, but was further reduced by either ETA/B-Ra or ECEi. The basal mean arterial blood pressure in control rats was unaffected by ETA-Ra, was elevated by ETB-Ra, but was depressed by ETA/B-Ra and ECEi. All ET blockers maintained normal oxygen saturation in APAE. These results support a role for ETs in rat APAE, since ET blockers can attenuate the cardiopulmonary deterioration and blood gas exchange. However, modulation of the central hemodynamic profile is more complex and may limit the usefulness of some ET blockers.

Acute Disease↗

Coronary stenting in diabetic patients: Results from the ROSETTA registry.

OBJECTIVE: Diabetes mellitus is associated with high rates of restenosis and adverse outcomes after percutaneous transluminal coronary angioplasty (PTCA). It is unclear whether coronary stenting reduces adverse events in diabetic patients after PTCA. Our purpose was to determine whether coronary stenting improves clinical event rates in diabetic patients after PTCA. METHODS: The Routine Versus Selective Exercise Treadmill Testing After Angioplasty (ROSETTA) registry was a prospective multicenter observational study examining functional testing and adverse outcomes after successful PTCA. RESULTS: Among the 791 patients enrolled, 180 were diabetic. A total of 90 diabetics received stents while the remaining 90 patients did not. Baseline clinical characteristics were similar between the 2 groups of patients. However, patients with stents were more likely to have complex lesions, whereas those without stents were more likely to undergo atherectomy and have greater residual coronary stenosis. At 6-month follow-up, the composite end point defined as cardiac death, unstable angina, myocardial infarction, need for repeat PTCA, or coronary artery bypass graft surgery (CABG) occurred in 25.0% of stented and 22.2% of nonstented diabetic patients (P not significant [NS]). A multivariate logistic regression analysis showed that coronary stenting was not associated with a reduced incidence of the composite end point among diabetic patients (odds ratio 0.97, 95% CI 0.46-2.05, P NS). CONCLUSION: Coronary stenting does not improve clinical event rates in diabetic patients after PTCA.

Angioplasty, Balloon, Coronary↗

Survey of hospital doctors' attitudes and knowledge of oral conditions in older patients.

The study was designed to assess the views and knowledge of hospital doctors in general and geriatric medicine on oral health in older people. Eighty two doctors in general and geriatric medicine at two hospitals were shown 12 colour slides of oral mucosal conditions and asked to give a diagnosis for each slide and complete a questionnaire. Completed questionnaires with the answers to the coloured slides were returned completed by 70 doctors. The majority of doctors (84%) felt it was important to examine older patients' mouths, however only 19% (chi(2) p=0.0001) routinely do so. If asked to prescribe nystatin by the nursing staff, 30% said they would do so without examining the mouth itself. Only 9% of doctors knew that wearing dentures was a specific risk factor for oral candidiasis (chi(2) p=0.001). Altogether 56% of doctors did not feel confident in examining the oral cavity and most (77%) did not think they had had sufficient training in this examination. Only two doctors correctly diagnosed all of the slides. An early squamous carcinoma was misdiagnosed by 80% of the doctors (chi(2) p=0.0001). Hospital doctors do not routinely inspect older patients' mouths. Even if shown slides of typical oral mucosal lesions many hospital doctors are unable to diagnose them. Issues on training need to be addressed. From the patients' point of view a public health campaign is required to educate older people on the need for a regular dental review and be aware that doctors may not be able to diagnose serious oral conditions.

Aged↗

Primary right atrial synovial sarcoma manifesting as transient ischemic attacks.

Primary tumors of the heart are rare and most of them benign. The majority of benign cardiac tumors are myxomas while almost all malignant cardiac tumors are sarcomas. We present a case of primary right atrial synovial sarcoma, a form of sarcoma particularly rare in the heart. The tumor manifested clinically as transient ischemic attacks probably related to a patent foramen ovale allowing paradoxical tumor embolization.

Diagnosis, Differential↗

Biphasic release of immunoreactive endothelins following acute pulmonary thromboembolism in pigs.

The purpose of this investigation was to study the role of endothelins (ETs) in the pathogenesis of acute pulmonary thromboembolism (PTE). Eighteen piglets (20 +/- 3 kg) were anesthetized and ventilated with 100% oxygen, five of them then served as controls. Acute thromboembolic injury in the lung was induced by injecting 15-25 ml of preformed clots into the left lower lobar pulmonary artery during thoracotomy. Pulmonary arterial pressure (Ppa) increased by at least 2.5-fold from baseline. During the subsequent 8 h, seven blood samples were collected from the left atrium and assayed for immunoreactive ETs. The results showed that following PTE: (1) Ppa remained elevated but cardiac output remained constant throughout the experiments; (2) plasma level of immunoreactive ETs increased in the embolized group compared to controls and the profile of immunoreactive ET release suggested a biphasic response. We conclude that the release of these vasocontractile and bronchoconstrictive mediators after PTE may contribute to ventilation perfusion mismatching and account for the pulmonary hypertension and deterioration of gas exchange that are often seen clinically.

Acute Disease↗

Aneurysm after subclavian flap angioplasty repair of coarctation of the aorta.

We report a case of aortic aneurysm at the site of subclavian flap angioplasty repair for coarctation of the aorta. The dilatation involved the lateral wall of the proximal descending aorta that had been constructed by the flap. Five other similar cases have been reported in the literature. Diligent long-term follow-up is needed after surgical repair of coarctation of the aorta to detect late complications such as restenosis or aneurysm formation.

Adult↗

Patient-controlled analgesia in postoperative cardiac surgery.

The purpose of this study was to assess, in the early postoperative period of cardiac surgery, the efficacy of patient-controlled analgesia (PCA) versus nurse-administered intravenous morphine followed by oral acetaminophen with or without codeine. Patients undergoing coronary bypass and/or valvular surgery were recruited. All were under 75 years of age and were in stable angina with no ischaemic attacks within the last three months. Visual analog scores (VAS) were used for pain assessment. Pulmonary function tests were done preoperatively and measured every six hours after surgery until discharge from the intensive care unit. Patients allocated to the PCA group received morphine intravenously by a PCA Plus Micro Delivery Device for at least 48 hours. Patients entered into the nurse-administered intravenous morphine group received intravenous morphine followed by oral acetaminophen with or without codeine in 24 to 36 hours according to the clinical assessment of the critical care nurse. The data showed that the quality of pain control and pulmonary function were comparable in both groups. The equipotent morphine dosage requirements were also not statistically different. It was concluded that there was no significant advantage in using PCA routinely in the early postoperative period after cardiac surgery. Furthermore, repetition of PCA instructions was often required during the study period.

Acetaminophen↗

Electrostatics and the membrane association of Src: theory and experiment.

The binding of Src to phospholipid membranes requires both hydrophobic insertion of its myristate into the hydrocarbon interior of the membrane and nonspecific electrostatic interaction of its N-terminal cluster of basic residues with acidic phospholipids. We provide a theoretical description of the electrostatic partitioning of Src onto phospholipid membranes. Specifically, we use molecular models to represent a nonmyristoylated peptide corresponding to residues 2-19 of Src [nonmyr-Src(2-19); GSSKSKPKDPSQRRRSLE-NH2] and a phospholipid bilayer, calculate the electrostatic interaction by solving the nonlinear Poisson-Boltzmann equation, and predict the molar partition coefficient using statistical thermodynamics. The theoretical predictions agree with experimental data obtained by measuring the partitioning of nonmyr-Src(2-19) onto phospholipid vesicles: membrane binding increases as the mole percent of acidic lipid in the vesicles is increased, the ionic strength of the solution is decreased, or the net positive charge of the peptide is increased. The theoretical model also correctly predicts the measured partitioning of the myristoylated peptide, myr-Src(2-19); for example, adding 33% acidic lipid to electrically neutral vesicles increases the partitioning of myr-Src(2-19) 100-fold. Phosphorylating either serine 12 (by protein kinase C) or serine 17 (by cAMP-dependent protein kinase) decreases the partitioning of myr-Src(2-19) onto vesicles containing acidic lipid 10-fold. We investigated the effect of phosphorylation on the localization of Src to biological membranes by expressing fusion constructs of Src's N terminus with a soluble carrier protein in COS-1 cells; phosphorylation produces a small shift in the distribution of the Src chimeras from the plasma membrane to the cytosol.

Amino Acid Sequence↗

Attitudes toward life-sustaining treatment of older persons in Hong Kong.

OBJECTIVES: There have been few studies of the attitudes of older Asians toward life-sustaining therapy. This paper presents the knowledge of and attitudes toward cardiopulmonary resuscitation (CPR) and life support in a group of subjects in Hong Kong. DESIGN: Cross-sectional, descriptive study. PARTICIPANTS: Of the 543 subjects, 382 were old-age home residents and 161 were in-patients of geriatric wards. MEASUREMENTS: Sociodemographic data, functional ability (using the Barthel Index), self-perceived health scale, knowledge of life-sustaining procedures, and subjects' preferences for such treatments were studied. They were also asked to give the most important reason for wanting or declining CPR, and to indicate who they believe should be the decision-maker(s) regarding whether they should receive life-sustaining treatment. RESULTS: Approximately 80% of old-age home residents and 60% of hospitalized patients had no knowledge of life-sustaining therapy. The success rate of CPR was overestimated by older subjects, and most wished to be resuscitated. However, up to 20% changed their minds and declined CPR after they knew the true outcome of the procedure. Half of the subjects wanted life support. Univariate analysis found that advanced age and not having a spouse were associated significantly with CPR preference, whereas subjects' knowledge was associated with preference for life support. Multivariate analysis revealed that advanced age, not having a spouse, and female sex were independently associated with a tendency to decline CPR. A considerable proportion of older people wished to be involved in decision-making regarding life-sustaining treatment. CONCLUSION: Knowledge of life-sustaining procedures was poor among older people in Hong Kong compared with their counterparts in western countries. Although most older subjects wanted CPR, a number of them changed their minds after they knew the poor outcome. Therefore, older patients should be given more information about life-sustaining therapy and encouraged to take part in their treatment plans.

Activities of Daily Living↗

Specialization of the DNA-cleaving activity of a group I ribozyme through in vitro evolution.

In an earlier study, an in vitro evolution procedure was applied to a large population of variants of the Tetrahymena group I ribozyme to obtain individuals with a 10(5)-fold improved ability to cleave a target single-stranded DNA substrate under simulated physiological conditions. The evolved ribozymes also showed a twofold improvement, compared to the wild-type, in their ability to cleave a single-stranded RNA substrate. Here, we report continuation of the in vitro evolution process using a new selection strategy to achieve both enhanced DNA and diminished RNA-cleavage activity. Our strategy combines a positive selection for DNA cleavage with a negative selection against RNA binding. After 36 "generations" of in vitro evolution, the evolved population showed an approximately 100-fold increase in the ratio of DNA to RNA-cleavage activity. Site-directed mutagenesis experiments confirmed the selective advantage of two covarying mutations within the catalytic core of the ribozyme that are largely responsible for this modified behavior. The population of ribozymes has now undergone a total of 63 successive generations of evolution, resulting in an average of 28 mutations relative to the wild-type that are responsible for the altered phenotype.

Animals↗

Unusual trigonal-planar copper configuration revealed in the atomic structure of yeast copper-zinc superoxide dismutase.

The three-dimensional structure of yeast copper-zinc superoxide dismutase (CuZnSOD) has been determined in a new crystal form in space group R32 and refined against X-ray diffraction data using difference Fourier and restrained crystallographic refinement techniques. The unexpected result is that the copper ion has moved approximately 1 angstrom from its position in previously reported CuZnSOD models, the copper-imidazolate bridge is broken, and a roughly trigonal planar ligand geometry characteristic of Cu(I) rather than Cu(II) is revealed. Final R values for the two nearly identical room temperature structures are 18.6% for all 19 149 reflections in the 10.0-1.7 angstrom resolution range and 18. 2% for 17 682 reflections (F > 2 sigma) in the 10.0-1.73 angstrom resolution range. A third structure has been determined using X-ray data collected at -180 degrees C. The final R value for this structure is 19.0% (R(free) = 22.9%) for all 24 356 reflections in the 10.0-1.55 angstrom resolution range. Virtually no change in the positions of the ligands to the zinc center is observed in these models. The origin of the broken bridge and altered Cu-ligand geometry is discussed.

Crystallography, X-Ray↗