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Biomedical subjects

C K Li

Publications and source records attributed to C K Li.

At least 91 records · Page 5Linked to original sources

Bacteroides fragilis enterotoxin induces the expression of IL-8 and transforming growth factor-beta (TGF-beta) by human colonic epithelial cells.

Bacteroides fragilis toxin (BFT) has been shown to be capable of inducing intestinal mucosal inflammation in animals. Such inflammation may be responsible for diarrhoea, which occurs in some, but not all human carriers of enterotoxigenic strains of B. fragilis (ETBF). We have studied responses to BFT by different human intestinal epithelial cell lines and subsequently investigated the expression of IL-8 and TGF-beta by T84 cells. The latter were selected because their responses to BFT, characterized by morphological changes and cell death by apoptosis, were similar to those we have recently observed in primary human colonocytes. We show that BFT dose-dependently increased the expression of transcripts and protein of the polymorphonuclear cell chemoattractant IL-8. BFT also dose-dependently induced the release of TGF-beta, which has been shown to enhance the repair of the injured intestinal epithelium. However, the secreted TGF-beta was almost exclusively in the biologically inactive form, as determined by Mv1Lu bioassay. Our studies therefore suggest that exposure of colonic epithelial cells in vivo to high concentrations of BFT can initiate an inflammatory response via secreted IL-8. BFT-induced release of latent TGF-beta may facilitate the subsequent repair of the injured epithelium, following its activation by proteases from neighbouring cells. Variation in cytokine responses by colonic epithelial cells in vivo could be an important determinant in the development of mucosal disease and symptoms in response to ETBF.

Bacteroides fragilis↗

Desferrioxamine-induced long bone changes in thalassaemic patients - radiographic features, prevalence and relations with growth.

AIM: To study the radiographic findings of desferrioxamine-induced bone dysplasia, its prevalence and relation to growth in thalassaemic patients. MATERIALS AND METHODS: A cross-sectional study was performed in 35 thalassaemic patients on a hypertransfusion scheme and chelation therapy at a dose not exceeding 50 mg/kg/day. Radiographs of the left hand taken for bone age assessment in consecutive patients over the past 12 months were evaluated for signs of desferrioxamine-induced bone dysplasia. The findings were correlated with data on growth, chelation and body iron content. RESULTS: Twelve of 35 patients had evidence of desferrioxamine-induced long bone dysplasia. There was no significant difference in the groups with and without radiographic evidence of bone dysplasia with respect to the height percentile at time of initiation of therapy, height percentile at time of radiography, skeletal age delay, age at starting chelation, chelation dose and duration, units of blood transfused, average chelation dose, and serum ferritin levels at time of radiography. Both groups showed a reduced percentile growth with a significantly greater reduction (P = 0.03) in the patients with dysplastic change. CONCLUSION: Desferrioxamine-induced bone dysplasia is associated with height reduction and can be seen in patients receiving desferrioxamine chelation therapy at doses of less than 50 mg/kg/day. Awareness of the diagnosis is of importance as reduction of the desferrioxamine dose may improve bone growth.

Adolescent↗

Outcomes and prognostic factors of Chinese children with acute lymphoblastic leukemia in Hong Kong: preliminary results.

BACKGROUND: The Chinese population is the biggest ethnic group in the world. However, there are few reports on the treatment outcome of childhood acute lymphoblastic leukaemia (ALL) among the Chinese population. PROCEDURE: Sixty-five children with ALL were treated with a modified protocol of the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia protocol X(MRC UKALL X) at the Prince of Wales Hospital, Hong Kong. Most patients were ethnic Chinese. They were divided into groups A and B, depending on whether their presenting leucocyte count being was less or greater than 50 x 10(9)/l, respectively. Group A patients of received induction, early intensification (week 5), cranial irradiation, and maintenance for 3 years. Group B patients received an additional late intensification (week 20). RESULTS: The median follow-up duration was 6.8 years(range: 3.4-10.1 years). The event-free and overall survival rates of all patients at 7 years were 66% (confidence interval [CI] 53-76) and 75% (CI 63-84), respectively. The event-free survival rates of groups A and B at 7 years were 67% (CI 52-79) and 60% (CI 32-80), respectively (P= 0.39). The overall survival rates of groups A and B at 7 years were 80% (CI 66-89) and 60% (CI 32-80), respectively (P = 0.07). With this treatment protocol, the factors which adversely affected the outcome were age (<2 years and >10 years) and T-cell subtype. Sex, white blood count at diagnosis, and FAB subtypes were not statistically significant prognostic factors. CONCLUSIONS: The treatment outcomes were comparable with those reported from the MRC UKALL X trials.

Adolescent↗

Classifying the location of osteosarcoma with reference to the epiphyseal plate helps determine the optimal skeletal resection in limb salvage procedures.

Between 1989 and 1996, 21 skeletally immature patients were treated for osteosarcoma of the extremity. Their average age was 12.6 years (range 9-16 years). We classified the location and extent of the lesion in bone on magnetic resonance imaging (MRI) with reference to the growth plate and joint margin into five subtypes. This classification served as a guide for the level of resection and the type of reconstruction required for a limb salvage procedure. All patients received neoadjuvant chemotherapy using a modified T10 protocol before the definitive operation. These patients were followed up for periods ranging from 11-86 months, with a mean of 35. 5 months. Patients were assessed for (1) local tumour recurrence, (2) metastatic disease, (3) allograft complications and (4) extremity function and joint stability. Excellent function was retained in 2, good in 13 and fair function in 6 patients. The MRI classification proved useful for the resection and provides an insight into the possible functional outcomes.

Adolescent↗

The distribution of excretory/secretory antigens during the muscle phase of Trichinella spiralis and T. pseudospiralis infections.

The in situ distribution of excretory/secretory (ES) antigens of the infective-stage larvae of Trichinella spiralis and T. pseudospiralis was compared at various periods of development by immunofluorescent laser confocal microscopy and the immunoperoxidase method. In the former infection, epitopes of the ES antigens were always confined exclusively within the nurse cell, i.e., in the cytoplasmic region, hypertrophic nuclei, stichocytes, and cuticular surface of worms. In the latter infection, as early as at day 15 postinfection, ES epitopes were located along the infected myofibers, in the adjacent muscles, hypertrophic nuclei, stichocytes, and cuticular surface of worms. By day 30 postinfection there was a marked increase in both the distribution and the intensity of ES antigens in infected as opposed to uninfected myofibers. A new method was also developed to reveal the number of hypertrophic nuclei, small cells, and larvae in intact nurse cells. As many as four worms could be accommodated within a single complex. The number of hypertrophic nuclei within each complex varied from 15 to 81.

Animals↗

Ocular complications of pediatric bone marrow transplantation.

OBJECTIVE: To investigate the ocular complications in pediatric bone marrow transplantation (BMT) patients. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 29 pediatric BMT patients were studied. TESTING: Comprehensive ophthalmic check-up, including best-corrected visual acuity, intraocular pressure (IOP), Schirmer's test, tear breakup time, and slit-lamp and fundus examinations, was performed. MAIN OUTCOME MEASURES: Tear film instability and its related complications, IOP, cataract, and fundus lesions were measured. RESULTS: The mean age of patients was 9.1 years (range, 1.5-15 years). The mean post-BMT duration was 20.2 months (range, 3-54 months). Fifteen patients (51.7%) had tear abnormalities. Subconjunctival fibrosis was detected in two patients (6.9%). Dry and scaly skin of the eyelids was seen in one patient (3.4%). Lens opacities were found in 2 (33.3%) of 6 irradiated patients and 2 (8.7%) of 23 nonirradiated patients. Two patients (6.9%) had fundus changes, one with unilateral epiretinal membrane and the other with bilateral multiple discrete chorioretinal hypopigmented lesions in the middle to peripheral part of the retina. The overall complication rates for the anterior and posterior segments were 75.8% and 6.9%, respectively. CONCLUSION: Ocular manifestations of BMT in children are not uncommon. The most common anterior segment problem is tear dysfunction. Posterior segment complications are less common but do exist. High rate of cataract formation is reported, and this probably is the most important long-term "amblyogenic" problem in these immature eyes. Awareness and management of these problems with routine eye examination and early intervention are recommended.

Adolescent↗

Granulocyte colony-stimulating factor-mobilized peripheral blood stem cells in beta-thalassemia patients: kinetics of mobilization and composition of apheresis product.

beta-Thalassemias are often associated with bone marrow expansion and immunomodulation in terms of lymphocyte subsets and cytokine levels in the peripheral blood. The mobilization of peripheral blood stem cells (PBSC) by cytokines in such a background has not been reported. If achieved, the apheresis product could be used as a stem cell back-up for beta-thalassemia patients prior to bone marrow transplant. PBSC collection may also become a means for providing stem and progenitor cells for gene manipulation and therapy of this disorder. The aim of the study was to assess the administration of G-CSF in mobilizing stem and progenitor cells in these patients and to compare the kinetics of CD34+ cells and lymphocyte subsets with those of healthy PBSC donors. Results showed that the CD34+ cells were effectively mobilized by G-CSF (10-16 micrograms/day per kg) in 20 thalassemia patients and 11 healthy donors. Although no significant difference was observed in levels of daily stem cell counts between the two groups of subjects, a 1 day delay in achieving peak levels of CD34+ cells was observed in the majority of thalassemia patients. The peak increase of CD34+ cells was 21.5 +/- 6.1-fold and 30.8 +/- 7.6-fold of the basal steady-state levels in thalassemia patients and healthy donors, respectively. Similar to the situation of healthy donors, G-CSF stimulated essentially the CD34+ cells and the myeloid lineage (granulocytes, monocytes) in thalassemia patients and had a slight effect on lymphocyte subsets (T-helper, T-suppressor, NK, and B cells) and activation (CD25, HLA-DR, and CD45RO). Compositions of the apheresis products, including CD34+CD38-, CD34+CD33+ and CD34+HLA-DR- cells, were similar in the two groups of subjects. Correlation studies showed that the level of CD34+ cells in the PB is a good indicator of that in the apheresis product (r = 0.88, p < 0.001). The study has demonstrated that under close monitoring of CD34+ cell levels in PB, the mobilization by G-CSF and collection of PBSC in beta-thalassemia patients are feasible.

Adolescent↗

Primary orbital Ewing's sarcoma: report of a case and review of the literature.

Primary orbital Ewing's sarcoma is a very rare condition. Since the first case was reported in 1950, only 7 other cases have been reported in the English literature. Herein we describe the ninth, the only bilateral and the youngest case of primary orbital Ewing's sarcoma occurring in a 2-year-old boy, who presented to us with bilateral painless proptosis. Tissue biopsy of the tumour was obtained through the nasal sinus. Immunohistological studies of the biopsy tissue confirmed the diagnosis of Ewing's sarcoma. No distant site of the tumour was found so this was considered a primary orbital tumour. Combined chemotherapy and radiotherapy without surgical resection achieved an encouraging result in that the patient has remained in remission for 30 months after completion of treatment. The successful use of combined chemotherapy and radiotherapy, without surgery, adds further support to evidence that surgical excision may be avoided in selected cases of primary orbital Ewing's sarcoma.

Antineoplastic Combined Chemotherapy Protocols↗

Busulphan level and early mortality in thalassaemia patients after BMT.

The aim of the study was to correlate busulphan (BU) levels of thalassaemia patients with outcome of allogeneic transplant. BU levels were measured by gas chromatography mass fragmentography. All patients received a standardised dose of BU 16 mg/kg, and cyclophosphamide 150 or 200 mg/kg. For area-under-the-curve analysis (AUC), blood samples were obtained at 0, 1, 2, 3, 4 and 6 h after the first and fifth dose for all patients, and additional levels were measured after ninth and/or 13th dose in most patients. Outcome parameters examined included veno-occlusive disease of liver (VOD), idiopathic interstitial pneumonitis, chimerism, and day 90 survival. Twenty consecutive thalassaemia patients who underwent haematopoietic stem cell transplantation were studied. The median age at transplant was 11.2 years (range 3-21 years). Mean BU AUC levels were correlated with age at transplant (r = 0.58, P = 0.007). Nine patients developed VOD and six had mixed chimerism, but these did not correlate with mean BU AUC level. Four patients died before day 50 from VOD and interstitial pneumonitis. Patients with BU AUC levels greater than the median (908 micromol x min/l) had significantly lower probability of survival at day 90 (60%), whereas patients with BU AUC level less than the median all survived beyond day 90. No patient had graft rejection. In conclusion, a high BU AUC level was associated with a higher treatment-related mortality in thalassaemia patients after transplant.

Adolescent↗

Ex vivo expansion of enriched CD34+ cells from neonatal blood in the presence of thrombopoietin, a comparison with cord blood and bone marrow.

Neonatal blood (NB) contains substantial numbers of stem and progenitor cells which decline rapidly after birth. Using a combination of cord blood (CB) and NB, we performed a successful, sibling transplant for a thalassaemia patient, leading to the proposal that NB could be used as an adjunct to CB for transplantation. This study was aimed at addressing the feasibility of expanding NB and thus minimizing the volume needed from a NB collection. In the presence of early acting cytokines interleukin-1beta (IL-1beta), IL-3, IL-6, stem cell factor (SCF), flt-3 ligand with and without thrombopoietin (Tpo), we compared the expansion capacity of CD34+ enriched cells from CB, NB and bone marrow (BM). Flow cytometry and colony-forming unit (CFU) analyses show that Tpo significantly increased the expansion of CD34+ cells from CB and NB to early and committed progenitors. No significant difference was observed between the expansion of CB and NB at 7, 14 or 21 days of culture in terms of CFU, CD34+ and CD61+ cell subsets. The expansion capacity of BM was significantly lower than that of NB or CB, possibly related to the low proportion of CD34+ CD38- cells observed at day 0. There was a relatively rapid expansion of NB which was evident at day 7 whilst the expansion of CB and BM remained low, suggesting a speedy maturation process in the postnatal infant. The expanded cells, being heterogeneous in their morphology and cell surface marker expression, were mostly of the myeloid lineage (CD45+, CD33+ and HLA-DR+). Our results showed that the expansion capacity of NB is comparable to that of CB and if transplanted, the expanded products of NB might contribute to the engraftment kinetics of the neutrophil and megakaryocyte lineage.

Antigens, CD34↗

Human neonatal blood: stem cell content, kinetics of CD34+ cell decline and ex vivo expansion capacity.

Haemopoietic stem cells are present in fetal blood but their levels decline rapidly in the peripheral circulation of the infant after birth. We previously reported a case of stem cell transplant in a beta-thalassaemia boy using a combination of the cord blood (CB) and neonatal blood (NB) of his sister. This transplant resulted in a successful engraftment. To investigate the possibility of using NB to supplement CB for related transplants, we further characterized stem and progenitor cells and lymphocyte subsets in 20 NB samples, comparing the findings with those in 20 CB samples. Our data showed that NB contained substantial levels of CD34+ cells, CD34+CD38- cells, colony-forming units-granulocyte macrophage (CFU-GM), colony forming units-erythroid (CFU-E), burst forming units-erythroid (BFU-E) and long-term culture initiating cells (LTCIC). NB was similar to CB in the levels of T lymphocytes, but the amounts of B lymphocytes and natural killer cells were higher in CB (P = 0.033, P= 0.001, respectively). The kinetics of CD34+ cells in NB was investigated in serial blood samples obtained from 10 full-term infants at 2, 4, 6, 8, 24 and 48h after birth. CD34+ cells decreased rapidly after birth, declining to only 30% of the 2h level at 48h (P<0012). The rate of decline was greatest in the first 4 h of life. NB from four infants was expanded by culturing the blood samples in the presence of thrombopoietin (Tpo), interleukin 1beta (IL1beta), IL-3, IL-6, flt-3 ligand and stem cell factor (SCF) for 7 d. This resulted in the increase of CD34+ cells, CFU-GM and CFU-MK by 271+/-179, 556+/-385 and 113+/-75 fold respectively. Three of the five samples expanded for 7 d contained LTCIC. These findings suggest that NB might be a supplementary or alternative source of stem cells to CB for transplant. The ethics and practicality of this approach deserve further exploration.

Antigens, CD34↗

A memory-based self-generated basis function neural network.

The paper presents a novel memory-based Self-Generated Basis Function Neural Network (SGBFN) that is composed of small CMACs. The SGBFN requires much smaller memory space than the conventional CMAC and has an excellent learning convergence property compared to multilayer neural networks. Each CMAC in the new structure takes a subset of problem inputs as its inputs. Several CMACs that have different subsets of inputs form a submodule and a group of submodules form a neural network. The output of a submodule is the product of its CMACs' outputs. Each submodule implements a self-generated basis function, which is developed during the learning. The output of the neural network is the sum of the outputs from the submodules. Using only a subset of inputs in each CMAC significantly reduces the required memory space in high-dimensional modeling. With the same size of memory, the new structure is able to achieve a much smaller learning error compared to the conventional CMAC.

Artificial Intelligence↗

Epidemiology of paediatric cancer in Hong Kong, 1982 to 1991. Hong Kong Cancer Registry.

OBJECTIVE: To review the data of paediatric cancer that had been collected by the Hong Kong Cancer Registry from 1982 through 1991. DESIGN: Cross-sectional retrospective study. SETTING: Hong Kong. PATIENTS: Children aged 15 years or younger. MAIN OUTCOME MEASURES: The types of cancer were classified into 12 diagnostic groups according to morphology (following the International Classification of Diseases for Oncology M-code). The incidences of the different types of cancer were obtained with reference to the Hong Kong population aged 15 years or younger. Data collected between 1989 and 1991 were checked by paediatric oncologists from the Hong Kong Paediatric Haematology and Oncology Study Group. RESULTS: A total of 1756 cases of paediatric cancer were registered during the 10-year period. The incidence of cancer was 144.3 new cases per million children. Leukaemia was the most common form of childhood cancer (40.0%), followed by brain tumour (16.3%), and lymphoma (10.8%). The relative frequencies of neuroblastoma (2.4%) and Wilms' tumour (3.5%) were lower than those reported from western countries. CONCLUSION: The incidences and types of paediatric cancer in Hong Kong are similar to those in western countries. Collaboration with paediatric oncology groups should provide more accurate information on the incidence and survival rates of children with cancer in Hong Kong.

Journal Article↗

The Xylum Clot Signature Analyzer: a dynamic flow system that simulates vascular injury.

The Xylum Clot Signature Analyzer (CSA) is an automated, user-friendly, benchtop analyzer that assesses platelet function and coagulation in non-anticoagulated whole blood under physiological flow and temperature conditions. From blood drawn in a single venipuncture, the CSA measures: a) the time for platelets to occlude holes "punched" in a blood conduit (platelet hemostasis time or PHT); b) collagen-induced thrombus formation (CITF) as blood flows in a channel containing a collagen fiber; and c) clotting time (CT). Micrographs show platelet-rich thrombi in the punched holes and on the collagen surface after a run. PHT and CITF increased at lower shear rate, suggesting that shear activation of platelets is involved in hole closure and in collagen-induced thrombus formation. In blood mixed with anti-von Willebrand's factor (vWF) antibodies, anti-GPIb antibodies, aurin tricarboxylic acid (ATA), or anti-GPIIb-IIIa, PHT and CITF were prolonged, further supporting the reflection of platelet function by those parameters. At low shear rate (<1000 sec(-1)), native blood and blood treated with anti-vWF did not have significantly different PHTs or CITFs. At high shear rate (>6000 sec(-1)), the PHT and CITF of the anti-vWF-treated sample were significantly greater than those of the untreated sample. This supports the inhibition of shear-induced activation of platelets by anti-vWF in the CSA. Heparin-treated blood showed significantly longer CT, indicating that coagulation of blood under flow is inhibited by heparin. The CSA thus assess multiple aspects of hemostasis under near-physiological conditions.

Biological Assay↗

Allogeneic peripheral blood stem cell transplant in children.

Allogeneic peripheral blood stem cell (PBSC) transplant has recently been introduced for the treatment of hematological malignancies. As the data were limited mainly to adult patients, this study aimed to assess the feasibility and safety of this procedure in pediatric patients and donors. Eleven children aged 2-16 years received allogeneic PBSC transplant for acute lymphoblastic leukemia (n = 4), acute myeloid leukemia (n = 1), myelodysplastic syndrome (n = 1), severe aplastic anemia (n = 3), and thalassemia (n = 2). Nine donors were human leukocyte antigen (HLA)-identical siblings and the other two were one antigen mismatched family members. Eight donors were younger than 18 years old (10 months to 17 years). Donors were primed with granulocyte colony-stimulating factor (G-CSF) at 10-16 micrograms/kg for 4-5 days. Aphereses were performed on 1 or 2 consecutive days, and the patients received a mean of 14.4 x 10(8)/kg nucleated cells, 6.9 x 10(6)/kg CD34 cells, and 6.9 x 10(8)/kg T cells. All patients achieved neutrophil counts of > 0.5 x 10(9)/l at a median of 16 days. Nine patients achieved platelet counts of > 20 x 10(9)/l at a median of 13 days. Grade II acute graft vs. host disease (GVHD) occurred in only one patient. Chronic GVHD was not observed in the seven patients with follow-up of more than 3 months. Eight patients remained in continuous complete remission after transplant ranged from 2 to 26 months. Allogeneic PBSC transplant appears safe in pediatric patients and donors, and it seems not to be associated with increase of acute GVHD or chronic GVHD.

Adolescent↗