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L S Chan

Publications and source records attributed to L S Chan.

At least 19 recordsLinked to original sources
PubMed2006

A comparison of sirolimus vs. calcineurin inhibitor-based immunosuppressive therapies in liver transplantation.

BACKGROUND: Sirolimus is a potent immunosuppressive agent whose role in liver transplantation has not been well-described. AIM: To evaluate the efficacy and side-effects of sirolimus-based immunosuppression in liver transplant patients. METHODS: Retrospective analysis of 185 patients who underwent orthotopic liver transplantation. Patients were divided into three groups: group SA, sirolimus alone (n = 28); group SC, sirolimus with calcineurin inhibitors (n =56) and group CNI, calcineurin inhibitors without sirolimus (n = 101). RESULTS: One-year patient and graft survival rates were 86.5% and 82.1% in group SA, 94.6% and 92.9% in group SC, and 83.2% and 75.2% in group CNI (P = N.S.). The rates of acute cellular rejection at 12 months were comparable among the three groups. At the time of transplantation, serum creatinine levels were significantly higher in group SA, but mean creatinine among the three groups at 1 month was similar. More patients in group SA required dialysis before orthotopic liver transplantation (group SA, 25%; group SC, 9%; group CNI, 5%; P = 0.008), but at 1 year, post-orthotopic liver transplantation dialysis rates were similar. CONCLUSIONS: Sirolimus given alone or in conjunction with calcineurin inhibitors appears to be an effective primary immunosuppressant regimen for orthotopic liver transplantation patients. Further studies to evaluate the efficacy and side-effect profile of sirolimus in liver transplant patients are warranted.

Blood Cell Count↗
PubMed2006

Autoimmunity to type VII collagen in SKH1 mice is independent of regulatory T cells.

Epidermolysis bullosa acquisita is an autoimmune blistering disease characterized by circulating and skin basement membrane-bound IgG autoantibodies to type VII collagen, a major structural protein of the dermal-epidermal junction. Regulatory T cells (T(reg)) suppress self antigen-mediated autoimmune responses. To investigate the role of T(reg) in the the autoimmune response to type VII collagen in a mouse model, a monoclonal antibody against mouse CD25 was used to deplete T(reg). A recombinant mouse type VII collagen NC1 domain protein and mouse albumin were used as antigens. SKH1 mice were used as a testing host. Group 1 mice received NC1 immunization and were functionally depleted of T(reg); group 2 mice received NC1 immunization and rat isotype control; and group 3 mice received albumin immunization and were functionally depleted of T(reg). Results demonstrated that anti-NC1 IgG autoantibodies with high titres, as determined by enzyme-linked immunosorbent assay and Western blotting, developed in all mice immunized with NC1 (groups 1 and 2), but were undetected in group 3 mice. The predominant subclasses of anti-NC1 autoantibodies were IgG1, IgG2a and IgG2b; furthermore, these antibodies carried only the kappa light chain. IgG autoantibodies in the sera of NC1-immunized mice reacted with mouse skin basement membrane in vitro and deposited in skin basement membrane in vivo as detected by indirect and direct immunofluorescence microscopy, respectively. Our data suggest that the development of autoimmunity against type VII collagen in mice is independent of T(reg) function and the autoimmune response is mediated by both Th1 and Th2 cells. We speculate that the basement membrane deposition of IgG may eventually lead to blister development.

Animals↗
PubMed2006

The prognostic impact of the time interval to recurrence for the mortality in recurrent colorectal cancer.

OBJECTIVE: The risk of a cancer recurrence has been correlated with the stage of the primary tumour at the time of presentation. However, once a recurrence has developed, the primary tumour stage may not be the determining prognostic factor anymore. The objective of this study was (i) to evaluate the association between the recurrence interval and the outcome of the recurrence, and (ii) to determine whether that interval was affected by the use of adjuvant radiation and/or chemotherapy. METHOD: This retrospective study analysed 212 patients who developed recurrent colorectal cancer from 1987 to 1993. Primary parameters such as age, gender, primary tumour site and stage, and use of postoperative adjuvant treatment were correlated with the recurrence interval, the type and site of the recurrence (i.e. locoregional vs distant metastases), and the outcome. Uni- and multivariate analysis was used to compare the recurrence interval and survival between different subgroups as defined by risk factors. RESULTS: The mean time between the primary and the recurrent tumour was 25 months (range 1-252 months) with 82% of the recurrences developing within 3 years after surgery. The recurrence interval was inversely correlated with the initial tumour stage. Poor survival was associated with a short recurrence interval (less than 12 months) and a distant recurrence site. Even after adjusting for the initial tumour stage, the use of adjuvant treatment did not prolong the interval, i.e. delay the onset of recurrent cancer. CONCLUSION: The recurrence interval of colorectal cancer is a prognostic factor. However, the use of adjuvant therapy did not prolong that interval.

Adult↗
PubMed2006

Treatment of diarrhea-predominant irritable bowel syndrome with traditional Chinese herbal medicine: a randomized placebo-controlled trial.

BACKGROUND: As there is no effective treatment for irritable bowel syndrome (IBS), many patients turn to traditional Chinese medicine (TCM) for possible cure. We investigated the therapeutic efficacy of an ancient herbal Chinese formula in patients with diarrhea-predominant IBS. METHODS: This was a randomized double-blinded placebo-controlled trial. Chinese IBS patients with predominant diarrhea symptoms that fulfilled Rome II criteria were recruited. The diagnosis was verified by a TCM herbalist using TCM criteria. Eligible patients were randomized to receive a standard preparation of TCM extracts that contained 11 herbs or placebo with similar appearance and taste for 8 wk after a 2-wk run-in period. Patients were followed up for an additional 8 wk post-treatment. Primary outcome was patient's global symptom assessment. Other outcome measures included individual IBS symptom scores and health-related quality of life (short form 36). RESULTS: One hundred nineteen patients were randomized: 60 to receive TCM and 59 to receive placebo. There was no significant difference in the proportion of patients with global symptom improvement between the TCM and placebo groups at week 8 (35% vs 44.1%, p = 0.38) and at week 16 (31.7% vs 33.9%, p = 0.62). Moreover, there was no difference in individual symptom scores and the quality-of-life assessment between the two groups at all time points. BACKGROUND: The use of this herbal formulation for diarrhea-predominant IBS did not lead to global symptom improvement. Further controlled clinical studies may be necessary to characterize the role of TCM in the management of IBS.

Adolescent↗
PubMed2005

Correlation of disease evolution with progressive inflammatory cell activation and migration in the IL-4 transgenic mouse model of atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration in the skin. In order to assess the roles of inflammatory cells in this disease, we analysed the activation status and surface markers of various leucocytes in the IL-4 transgenic mouse model of atopic dermatitis, by flow cytometry, immuofluorescence microscopy, and T cell proliferation assays. The studies were performed with a nontransgenic mouse control and transgenic mice at three disease stages: before disease onset, early skin disease, and late skin disease, so that we can delineate the immunological sequence of events. As the skin disease evolves, the skin draining lymph node cells from IL-4-Tg mice show a spontaneous proliferation and a progressively enhanced proliferative response to stimulants including anti-CD3, Con A, PHA, and Staphylococcus enterotoxins A and B. As the disease evolves, the percent of lymphoid organ T cells expressing activation molecules (CD44 and CD69) and costimulatory molecules (ICOS and PD-1) are progressively increased; the percent and total number of T cells are reduced in an incremental manner in the secondary lymphoid organs while the number of T cells infiltrating the skin increases in an incremental fashion; the total number of dendritic antigen presenting cells, macrophages, and NK cells gradually increases in the lymphoid organs. Collectively, our results suggest that there is a continued and progressive migration of activated inflammatory cells from the secondary lymphoid organs into the skin where they participate in immune responses resulting in the pathology associated with inflammation.

Animals↗
PubMed2005

The disease progression in the keratin 14 IL-4-transgenic mouse model of atopic dermatitis parallels the up-regulation of B cell activation molecules, proliferation and surface and serum IgE.

We have previously characterized the keratin 14 interleukin-4-transgenic (IL-4-Tg) mouse model of atopic dermatitis as a chronic pruritic inflammatory skin disease typified by skin infiltration of inflammatory cells and early up-regulation of Th2 cytokines and late surge of Th1 cytokines. In the present study, we examined the involvement of B cells. Systematic examinations of the following immunological parameters on B cells were carried out in non-Tg control mice and in IL-4-Tg mice at before disease onset and early and late disease stages so that we could determine the immunological sequence of events leading to the disease development: surface expressions of IA/IE, activation and costimulatory molecules, proliferation under LPS or IgM stimulation, quantification of cell surface and serum IgE, IgG1, and IgG2a. Our results showed that as the disease progresses from before onset to early disease and to late disease, there is a parallel increase in surface markers of B cell activation (IA/IE, CD44, CD69, CD80 and CD86), in B cell proliferation, and in cell surface and serum IgE. Significant increases of Th2-driven serum IgG1 and IgE in early disease was followed by significant increase of Th1-driven IgG2a in late disease. Importantly the significant increases of activation molecule (IA/IE), proliferation (to LPS), and surface IgE on B cells of the IL-4-Tg mice precedes the up-regulation of serum IgE and disease onset. These data suggest that activated B cells may play a role in atopic dermatitis disease development by up-regulating serum IgE concentration, which serves as a marker of disease onset.

Animals↗
PubMed2004

Agreements among traditional Chinese medicine practitioners in the diagnosis and treatment of irritable bowel syndrome.

BACKGROUND: Traditional Chinese Medicine was frequently used by patients with irritable bowel syndrome. AIM: To evaluate the agreement on diagnoses and prescription of irritable bowel syndrome among Traditional Chinese Medicine practitioners. METHODS: Consecutive irritable bowel syndrome patients were interviewed independently by four Traditional Chinese Medicine practitioners. The study was divided into three phases: (i) blinded individual assessment, (ii) discussion to achieve consensus on diagnosis and treatment, (iii) individual assessment based on consensual diagnostic criteria. Patients with other causes of diarrhoea were recruited as controls in phase (iii). Percentage agreement and kappa-value in diagnosis, treatment principle and regime were determined. RESULTS: Thirty-nine irritable bowel syndrome patients were assessed in phase (i) whereas 65 irritable bowel syndrome patients and 17 non-irritable bowel syndrome controls were studied in phase (iii). The mean agreement rates in diagnosis, treatment principle and regimen were: 57, 58 and 52% for phase (i) and 80, 81 and 80% for phase (iii) (P = 0.002). Accordingly, there was significant improvement in the mean kappa-values in diagnosis (0.11-0.34, P = 0.015) and treatment principle (0.16-0.37, P = 0.002) but not in treatment regime. CONCLUSIONS: Variations in diagnosis and treatment principles do exist among Traditional Chinese Medicine practitioners. Concordant diagnosis can be reached by mutual understanding and converging opinion among Traditional Chinese Medicine practitioners.

Adult↗
PubMed2004

Early up-regulation of Th2 cytokines and late surge of Th1 cytokines in an atopic dermatitis model.

We investigated cytokine profiles in interleukin (IL)-4 transgenic (Tg) mice with a skin inflammatory disease resembling human atopic dermatitis. cDNA microarray revealed that the mRNAs encoding IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-13, tumour necrosis factor (TNF)-alpha, TNF-beta and interferon (IFN)-gamma were up-regulated in the skin of late lesion Tg mice and to a lesser degree in non-lesion Tg mice when compared to those of non-Tg mice. Real time reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated that the cDNA copy numbers of IL-1beta, IL-4, IL-6, IL-10, TNF-alpha and IFN-gamma from the skin of late, early and non-lesions increased significantly compared to non-Tg mice. IL-2 and IL-12p40 cDNA copy numbers were increased significantly in early, but not late, lesions. Interestingly, IL-1beta, IL-3, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-alpha, and IFN-gamma cDNAs were increased significantly the skin of before-onset and/or non-lesion mice. Flow cytometry analyses demonstrated an increased percentage of keratinocytes producing IL-4 as the disease progressed. The percentage of IL-2, IL-4, IL-10 and IFN-gamma-producing T cells and IL-12-producing antigen-presenting cells in skin-draining lymph nodes and inflammatory skin also increased, particularly in mice with late lesion. These results suggest that disease induction is primarily triggered by Th2 cytokines and that Th1, Th2 and non-Th proinflammatory cytokines are all involved in the disease process.

Animals↗
PubMed2002

Expression of eotaxin, an eosinophil-selective chemokine, parallels eosinophil accumulation in the vesiculobullous stage of incontinentia pigmenti.

Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis primarily affecting female children. The initial vesiculobullous stage of IP is characterized clinically by inflammatory papules, blisters, and pustules, and histopathologically by acanthosis, keratinocyte necrosis, epidermal spongiosis and massive epidermal eosinophil infiltration. The cause of this multisystem disease is attributed to the mutations of an X-linked regulatory gene, termed nuclear factor-kappaB essential modulator (NEMO). The exact mechanism of epidermal eosinophil accumulation has not yet been determined. We explored the possible role of an eosinophil-selective, nuclear factor-kappaB-activated chemokine, eotaxin, in the accumulation of eosinophils in the initial stage of the disease. Monoclonal antibody (6H9) specific for human eotaxin strongly labelled the suprabasal epidermis of IP skin, paralleling the upper epidermal accumulation of eosinophils, but did not label the epidermis of normal skin or lesional skin from patients with other inflammatory skin diseases not characterized by prominent eosinophil accumulation, namely dermatitis herpetiformis and selected cases of atopic dermatitis lacking significant numbers of eosinophils. In addition, endothelial cells in lesional skin of IP also exhibited strong expression of eotaxin, which correlated with perivascular and intravascular eosinophil infiltration. We also examined the in vitro effects on epidermally derived eotaxin of several cytokines that were nuclear factor-kappaB-activated and/or known to induce eotaxin expression. In normal human keratinocytes, proinflammatory cytokines either independently (IL-1alpha) or synergistically (tumour necrosis factor-alpha (TNF-alpha)/ interferon-gamma (IFN-gamma) and TNF-alpha/IL-4) up-regulated eotaxin expression. These studies suggest that release of cytokines during the initial inflammatory stage of IP induces epidermal expression of eotaxin, which may play a role in the epidermal accumulation of eosinophils.

Cells, Cultured↗
PubMed2001

Characterization of BALB/c mice B lymphocyte autoimmune responses to skin basement membrane component type XVII collagen, the target antigen of autoimmune skin disease bullous pemphigoid.

Bullous pemphigoid is an autoimmune blistering skin disease characterized by IgG autoantibodies targeting the skin basement membrane component type XVII collagen (BPAg2). To gain understanding of the disease's induction phase, we subcutaneously immunized adult BALB/c mice with peptides of human and/or the murine-equivalent BPAg2 pathogenic NC16A domain. Female mice were injected with peptides (human, murine, or combined human and murine), or PBS control emulsified in CFA, on a four-week interval. At the fourth and subsequent immunizations, all peptide-immunized mice were given murine peptides. Two weeks after the sixth immunization, ELISA detected IgG circulating autoantibodies against self peptides in 92% (47/51) of mice immunized with murine peptides; whereas none of the preimmune sera or the sera from PBS control-immunized mice reacted to the self peptides. In four mice their autoantibodies labeled mouse skin basement membrane. Breaking B-cell tolerance to BPAg2 sets the first step in dissecting the disease's induction phase.

Amino Acid Sequence↗
PubMed2001

A spontaneous canine model of mucous membrane (cicatricial) pemphigoid, an autoimmune blistering disease affecting mucosae and mucocutaneous junctions.

Mucous membrane pemphigoid (MMP) is a rare autoimmune blistering dermatosis of humans that was previously known as cicatricial pemphigoid. It is characterized by vesicles, ulcers and scarring that affect predominantly mucosae and mucocutaneous junctions. Circulating autoantibodies recognize epitopes on basement membrane proteins such as collagen XVII or laminin-5/6. Herein, we describe the clinico-pathological and immunological characteristics of 17 dogs afflicted with a dermatosis homologous to MMP of humans. Patients exhibited vesicles and erosions predominantly on mucous membranes or mucocutaneous junctions of the mouth, nose, eyes, genitalia or anus. Histopathology revealed subepithelial vesicles with variable dermal inflammation. Direct immunofluorescence demonstrated IgG or complement at the dermoepithelial junction. Indirect immunofluorescence using salt-split epithelia permitted the detection of circulating basement membrane-specific IgG autoantibodies in 15 cases. In 11 patients, autoantibodies recognized the NC16A segment of collagen XVII, as determined by salt-split indirect immunofluorescence, immunoblotting using canine keratinocytes and ELISA with synthetic canine peptides. In one dog, autoantiodies bound to the dermal side of salt-split epithelia and recognized epitopes within the 30 kDa carboxy-terminal segment of human collagen XVII. Canine MMP, like its human counterpart, exhibits distinctive clinical signs and histopathological lesions, yet circulating autoantibodies target different antigenic epitopes. This spontaneous canine model of MMP could prove useful for studies on the pathogenesis or therapy of this human disease.

Animals↗
PubMed2001

Magnetic properties and heavy-metal contents of contaminated seabed sediments of Penny's Bay, Hong Kong.

Magnetic properties and heavy-metal concentrations of vibrocore samples were found to be potential indicators of shipping contamination in seabed sediments in Hong Kong Harbour. Geochemical results of 74 vibrocores located off Penny's Bay on Lantau Island revealed an enrichment of heavy metals in the upper 1-2 m of the cores within the eastern part of the study site. Whole-core magnetic susceptibility measurements also showed a greater concentration of magnetic particles in the surficial layer of these cores. A significant correlation exists between the magnetic susceptibility and the concentrations of Pb, Zn and Cu, as well as the Tomlinson pollution load index (PLI). The proximity of these cores to a major navigation fairway and an anchorage site suggests probable contamination of the surficial seabed sediments by shipping-related wastes. A study of the magnetic properties of one of the cores, VT60, revealed a difference in the magnetic properties between the contaminated and the uncontaminated sediments. Samples from the contaminated zone exhibited relatively stronger magnetic remanence and susceptibility. The two groups of samples also formed distinct trends on the hysteresis ratios plot. A level of unusually high magnetic susceptibility within the contaminated zone was attributable to the presence of strongly magnetized granules, which were probably refuse from shipping-related activities. Geochemical and magnetic results were also conducted on samples of different size-fractions from this core. The < 63 microns fraction was found to contain a relatively higher magnetic susceptibility and greater heavy-metal content.

Environmental Monitoring↗
PubMed2001

"Insignificant" mechanism of injury: not to be taken lightly.

BACKGROUND: Trauma resources should be spent rationally. The mechanism of trauma is used extensively to triage patients to appropriate levels of care. We examine the hypothesis that patients with "insignificant" mechanism of trauma may have major injuries that require expert trauma care. STUDY DESIGN: Over 9 months at a high-volume Level I trauma center, a prospective study was done on patients who sustained ground-level falls (GLF), low-level falls (LLF) from less than 10 feet, or were found down (FD) with no external evidence of significant trauma, and required evaluation by the trauma team. Of 301 patients included, 110 (37%) had GLF, 95 (31%) LLF, and 96 (32%) FD. Our main outcomes measure was significant injuries, defined as visceral or intracranial injuries, long-bone, pelvic, facial, or spinal fractures. RESULTS: One hundred ten patients (37%) had significant injuries, 20 (7%) were admitted to the ICU, 14 (5%) required an operation, and 4 (1%) died. The most common injuries were intracranial and skeletal. Almost all patients were evaluated by CT (95%), but only one-quarter had abnormal findings on it. LLF, age more than 55 years, and the absence of severe intoxication (blood alcohol level of less than 200 mg/dL) were independent risk factors for significant injuries. A statistical prediction model showed that, when all risk factors are present, the probability of significant injuries is 73%; when all risk factors are absent, there is still a 16% chance for significant injuries. Patients with significant injuries had more operations, longer hospital stays, and higher hospitalization costs compared with patients without significant injuries. CONCLUSIONS: Low-energy trauma may produce significant injuries, predominantly intracranial and skeletal. Trauma care providers should be cautious about dismissing such patients based on the trivial mechanism of injury. Patients with LLF who are older than 55 years and not severely intoxicated have a high likelihood for significant injuries. Resources should be spent rationally for patients who do not have these characteristics, because the probability of significant injuries among them is low, but not zero.

Abdominal Injuries↗
PubMed2001

Nursery survival for infants of birth weight 500-1500 grams during 1982-1995.

OBJECTIVE: To evaluate nursery survival of very low birth weight infants (VLBW) over time, born in the same large inner-city hospital with a predominantly Hispanic population. METHODS: All liveborn VLBW infants weighing 500-1500 g at birth were included in four time periods of 2 years' duration during 1982 to 1995. Demographics were collected for the obstetric population. Clinical data were collected including maternal and infant perinatal factors. All infants were assigned a cause of death and infants dying with lethal anomalies were then excluded from further evaluations. RESULTS: Overall survival improved progressively (p = 0.0001) with dramatic improvement in survival of infants 500-750 g birth weight (BW) in period 4 (1994-1995). The number of lethal anomalies did not increase but accounted for a larger portion of deaths in period 4. Decreases in other causes of death over time reflected changes in perinatal care. Although the mothers were high-risk, none of the maternal factors evaluated showed any consistent effect on infant survival. Improved labor and delivery care was associated with improvement in Apgar scores, a decrease in intracranial hemorrhage/intraventricular hemorrhage as a cause of death and an improvement in survival between the first two periods. In spite of the increase in Cesarean sections for infants of 500-750 g BW and their improved survival in period 4, no clear advantage for Cesarean section could be demonstrated. The marked improvement seen in period 4 was associated with three changes in care: increased use of maternal steroids, administration of surfactant, and the use of newer ventilatory methods including high-frequency oscillatory ventilation. Although female gender has been reported to confer a protective influence for survival, this was not found in the final period. Black mothers comprised only about 2.5% of the total obstetric population but delivered approximately 10% of the VLBW infants. Despite the increased incidence of small for gestational age (SGA) among black infants, there were no differences in survival between blacks and Hispanics. Mean birth weight and gestational age in both survivors and nonsurvivors decreased significantly over the four time periods. In period 4, 50% survival occurred at a birth weight of 600-700 g and a gestational age of 23 weeks. CONCLUSION: Nursery survival improved throughout the period of the study from 1982 to 1995 but especially during period 4 (1994-1995). Improved survival was associated with changes in both maternal and infant care. In infants of BW 500-750 g, gestational age rather than birth weight was more closely associated with survival.

Black or African American↗
PubMed2001

Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis.

Atopic dermatitis, a common, chronic, inflammatory skin disease that occurs with increasing prevalence, is characterized by hyperactivated cytokines of helper T cell subset 2 and is frequently associated with staphylococcal infection. An experimental animal model of atopic dermatitis induced by transgenically introduced cytokine is not available. We generated a transgenic mouse line expressing epidermal interleukin-4, a critical cytokine of helper T cell subset 2. Here we show that transgenic mice spontaneously developed a pruritic inflammatory skin disease reproducing all key features of human atopic dermatitis, including xerosis, conjunctivitis, inflammatory skin lesions, Staphylococcus aureus infection, histopathology of chronic dermatitis with T cell, mast cell, macrophage-like mononuclear cell, and eosinophil infiltration, and elevation of total serum IgE and IgG1. The onset and early progression of skin disease coincided with increased total serum IgE and IgG1. The mouse disease occurred at a 43% annual incidence rate and primarily affected the poorly haired skin: ear (100%), neck (65%), eye (53%), face (29%), tail (12%), leg (12%), and torso (6%). As a group the affected transgenic mice manifested with a skin disorder that fulfilled the clinical diagnostic criteria established for atopic dermatitis in human patients. Pending further characterization to authenticate it as a model of atopic dermatitis, this experimental animal model of pruritic inflammatory skin disease may facilitate investigations for the roles of interleukin-4 in cutaneous inflammation and skin infection in human patients.

Animals↗