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Biomedical subjects

T M Chan

Publications and source records attributed to T M Chan.

At least 73 records · Page 4Linked to original sources

Changes of cytokine profiles during peritonitis in patients on continuous ambulatory peritoneal dialysis.

Continuous ambulatory peritoneal dialysis (CAPD) has emerged as an important dialysis treatment modality worldwide. One of the major complications is bacterial peritonitis, which may result in subsequent technique failure because of loss of peritoneal clearance or peritoneal fibrosis. Bacterial peritonitis leads to the release of proinflammatory cytokines from resident and infiltrating cells in the peritoneal cavity. We studied 35 patients undergoing CAPD with acute bacterial peritonitis. All patients treated with antibiotics for 2 weeks after the clinical diagnosis of peritonitis had a good recovery. Peritoneal dialysate effluent (PDE) was collected on days 1, 3, 5, 10, 21, and 42 after the start of treatment. Cell populations were monitored by flow cytometry. PDE levels of interleukin-1beta (IL-1), IL-6, transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (FGF) were measured by enzyme-linked immunosorbent assay. Gene transcription of TGF-beta in macrophages from PDE was measured by quantitative polymerase chain reaction. Bacterial peritonitis was associated with a sharp increase in total cell and neutrophil counts (400-fold) in PDE up to 3 weeks after peritonitis despite clinical remission (P < 0.0001). There was an increased absolute number of macrophages during the first 3 weeks despite the reduced percentage of macrophages among total cells in PDE compared with noninfective PDE. There was a progressive increase in the percentage of mesothelial cells or dead cells in the total cell population in PDE over the entire 6-week period. PDE levels of IL-1, IL-6, TGF-beta, and FGF increased markedly on day 1 before their levels decreased gradually. PDE levels of these cytokines or growth factors were significantly greater than those in noninfective PDE (n = 76) throughout the study period (P < 0.01). Similarly, TGF-beta complementary DNA (cDNA) molecules per macrophage were significantly greater than those of macrophages in noninfective PDE throughout this period (P < 0.01). There was no significant correlation between PDE levels of TGF-beta and TGF-beta cDNA molecules per macrophage, suggesting that peritoneal macrophages are not the only source of TGF-beta in PDE. We conclude there is an active release of proinflammatory cytokines and sclerogenic growth factors through at least 6 weeks despite apparent clinical remission of peritonitis. The peritoneal cytokine networks after peritonitis may potentially affect the physiological properties of the peritoneal membrane.

Bacterial Infections↗

Post-transplantation lymphoproliferative disease of natural killer cell lineage: a clinicopathological and molecular analysis.

Post-transplantation lymphoproliferative disorders (PTLD) occur after solid organ and bone marrow transplantation. They are predominantly of B-cell and occasionally of T-cell lineage. We report a case of PTLD of natural killer (NK) cell lineage. A renal allograft recipient developed progressive pancytopenia 1 year after transplantation. Serial bone marrow biopsies showed an increasing infiltration by large granular lymphoid cells. A subsequent leukaemic phase also developed with systemic infiltration of other organs. Immunophenotyping showed that these cells were CD2+, CD3-, CD3epsilon+, CD56+, CD94+, CD158a- and CD158b-. In situ hybridization showed Epstein-Barr virus (EBV) infection of the neoplastic cells. Genotypical analysis showed the T-cell receptor gene in germline configuration and clonal EBV episomal integration. The overall features were consistent with NK cell lymphoma/leukaemia. The patient did not respond to cessation of immunosuppression or anti-EBV treatment. Combination chemotherapy was given, but the patient died ultimately of disseminated fungal infection. In conclusion, we have demonstrated that NK cell lymphoma is another rare type of PTLD that appears to be highly aggressive and therefore may require early chemotherapy to improve treatment outcome.

Adult↗

Comparison of the CMV brite turbo assay and the digene hybrid capture CMV DNA (Version 2.0) assay for quantitation of cytomegalovirus in renal transplant recipients.

We compared the CMV Brite Turbo Kit (BT) and the Digene Hybrid Capture CMV DNA (version 2.0) assay (HC2) in the quantitation of pp65 antigenemia and cytomegalovirus (CMV) DNA levels in immunosuppressed renal transplant recipients. Of 123 blood specimens collected from 24 renal transplant recipients, BT and HC2 assays detected 35 and 39 positive samples, respectively. The overall concordance rate between the two assays was 90%. Discordant results were observed at low levels of viremia, so that 8 samples were HC2 positive but BT negative and another 4 were BT positive but HC2 negative. There was good correlation (R(2) = 0.766; P<0.01) between the levels of CMV DNA and pp65 antigenemia in the 31 concordant positive samples. Correlation between results obtained with the two assays was confirmed by longitudinal studies for a patient who developed clinical CMV disease. HC2 may be more sensitive at low viremia levels and allow earlier detection of impending CMV disease. The BT assay offered the advantage of a rapid (2-h) turnaround time. We conclude that BT and HC2 assays have similar sensitivity and efficacy in the diagnosis and monitoring of CMV infection and disease in renal transplant recipients. While the HC2 assay would be appropriate for centers that handle a large number of samples, the BT test may be more suitable for small sample numbers or when results are needed urgently.

Antigens, Viral↗

Oral health status, oral microflora, and non-surgical periodontal treatment of renal transplant patients receiving cyclosporin A and FK506.

OBJECTIVES: To determine the oral health status, oral microflora and the effect of non-surgical periodontal treatment on gingival overgrowth of renal allograft recipients receiving either cyclosporin A (CsA) or FK506 (Tacrolimus) as an immunosuppressant. MATERIALS AND METHODS: A total of 47 patients receiving CsA (mean age 43.1 years) and 10 receiving FK506 (mean age 40.1 years) were included in the study. Stone casts were taken for measurement of gingival overgrowth. An oral rinse technique was used to investigate the prevalence of yeasts, and aerobic and facultatively anaerobic Gram-negative rods (AGNR). RESULTS: The CsA and FK506 patients exhibited a Gingival Overgrowth Index (GOI) of 45.2%, and 25.1%, respectively (p < 0.05). The CsA patients had a GOI of 15.2% after one year of non-surgical periodontal treatment. The difference between pre- and postoperative gingival overgrowth indices was significant (p < 0.0001). Candida albicans and Klebsiella pneumoniae were the most notable yeast and AGRN found. CONCLUSIONS: Renal transplant patients, being immunocompromised, constitute a high-risk group for gingival overgrowth. However, the FK506 regime appeared to ameliorate this effect, compared with CsA. Non-surgical periodontal treatment was effective in reducing established gingival overgrowth in both CsA and FK506 patients (p < 0.05). Adequate pre- and post-transplant oral health care is recommended, for these patients, irrespective of the drug regime.

Adult↗

Chemical modifications and structure activity studies of ziracin and related everninomicin antibiotics.

Chemical modifications of eveminomicin antibiotics, particularly ziracin (1), were carried out to study the SARs as well as the chemical properties of this class of compounds. Use of allyl ether group for protection and selective deprotection of phenolic groups provided access to a variety of novel analogs of the title compounds, some of which exhibited the same high in vitro potency as the parent compounds.

Aminoglycosides↗

Early detection of hepatocellular carcinoma in hepatitis-B-positive renal transplant recipients.

Hepatocellular carcinoma (HCC) is a leading cause of malignancy after renal transplantation in Asia, where hepatitis B virus infection is endemic. Early detection and resection are the key to successful treatment because the mortality rate for HCC is high. The value of alpha-fetoprotein monitoring in the early detection of HCC in renal transplant recipients has not been reported before. We describe 2 patients who had successful resection of HCC following early diagnosis by alpha-fetoprotein monitoring. The epidemiology of post-transplant HCC in various parts of the world and its pathogenesis are discussed.

Carcinoma, Hepatocellular↗

Phenolic aporphine-benzylisoquinoline alkaloids from Thalictrum faberi.

From the roots of Thalictrum faberi, six new phenolic aporphine-benzylisoquinoline alkaloids, 3-hydroxy-6'-desmethyl-9-O-methylthalifaboramine (1), 3-hydroxythalifaboramine (2), 6'-desmethylthalifaboramine (3); 3,5'-dihydroxythalifaboramine (4), 5'-hydroxythalifaboramine (5) and 3-hydroxy-6'-desmethylthalifaboramine (6) were isolated. Their structures were established through the use of one- and two-dimensional NMR techniques. All of the tested alkaloids showed potent cytotoxic and antimalarial activities.

Alkaloids↗

Acute renal failure after immersion in seawater polluted by diesel oil.

Acute renal failure after exposure to toxic doses of hydrocarbon has been uniformly associated with multiorgan failure. We report a case of isolated acute renal failure in a patient after immersion in seawater polluted by diesel oil. The sites of absorption were likely to be skin, gastrointestinal tract, and lung. Investigations showed renal impairment as the only consequence from the exposure. The patient recovered uneventfully and did not require dialysis. This case highlighted the unusual consequence of isolated renal involvement resulting from hydrocarbon toxicity.

Acute Kidney Injury↗

Conformational considerations in the design of dual antagonists of platelet-activating factor (PAF) and histamine.

Following the discovery of the first dual antagonist of platelet-activating factor (PAF) and histamine, 1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin- 11-ylidene)piperidine, Sch 37370, 1, a related series of structures, exemplified by (+/-)-1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b] pyridin-11-yl)piperazine, Sch 40338, 2, were prepared. Interestingly, the compounds exhibited a parallel structure antiallergy activity relationship, suggesting that the two series may adopt a common conformation at the PAF receptor. Conformational analysis led to a proposal for this bioactive conformation accessible to both series. The synthesis of novel conformationally constrained analogues that might mimic the proposed bioactive conformation of these compounds, and the evaluation of their in vitro antiallergy activity form the subject matter of this report.

Animals↗

Helical computed tomography angiography in the evaluation of Chinese living renal donors.

OBJECTIVE: To determine the suitability of helical computed tomography angiography (CTA), recently used in the anatomical evaluation of potential living renal donors (LRDs) in the Caucasian population, for Chinese LRDs. SUBJECTS AND METHODS: Eighteen consecutive potential LRD candidates underwent both CTA and conventional renal angiography (CRA). Results from each were interpreted while unaware of the results from the other. Renal function was monitored after each radiological procedure. RESULTS: Both procedures were able to identify all four accessory renal arteries present. One prehilar branch of < 1 mm in diameter was not recognized on CTA. Renal artery ostial stenosis in one subject with normal blood pressure was identified on CTA, but not on CRA. CTA better delineated the renal venous and parenchymal anatomy and cost 60% less than CRA. There was no change in renal function after either procedure. CONCLUSION: Despite there being few subjects. CTA has potential value as an alternative to CRA for the anatomical assessment of potential LRDs in Hong Kong. Advantages include a short examination time, non-invasiveness and lower cost. CTA may provide an opportunity to living-related and unrelated renal donor transplantation in this conservative Chinese culture.

Adult↗

Lymphocyte subsets in renal allograft recipients with chronic hepatitis C virus infection.

BACKGROUND: The pathogenetic mechanisms of chronic hepatitis C virus (HCV) infection in renal allograft recipients are not well established. This study aimed to examine the relationship between altered immune status and HCV-related liver disease, by determining the changes in peripheral blood lymphocyte and natural killer (NK) cell subsets in these subjects. METHODS: Peripheral blood lymphocyte, NK cell and activation markers were detected by flow cytometry in renal allograft recipients with (TpC+) or without (TpC-) HCV infection, and compared with age- and sex-matched patients with post-transfusional chronic HCV infection (TfC+) and healthy controls. RESULTS: CD19+ cells were reduced in renal allograft recipients compared with controls. TpC+ subjects had increased CD3+CD8+ cells compared with controls, and increased CD3+DR+ cells but reduced CD4+ CD38+ and CD3-CD16/56+ cells compared with controls as well as TfC+ patients. TfC+ patients and controls had similar numbers and proportions for the lymphocyte subsets and NK cells. Chronic liver disease in HCV-infected renal allograft recipients was associated with increased CD3+CD16/56+ cells but reduced CD4+CD38+ cells. Reduction of CD3-CD16/56+ cells was noted in TpC+ subjects without liver disease. Yet among post-transfusional (TfC+) subjects this was associated with chronic hepatitis. CONCLUSIONS: Peripheral blood suppressor/cytotoxic T lymphocytes are increased, whereas activated helper/inducer T lymphocytes and NK cells are reduced, in renal allograft recipients with HCV infection. Increased non-MHC-restricted cytotoxic T cells and reduced NK cells are associated with the presence or absence of liver disease respectively. These data suggest that immune mechanisms are important in the pathogenesis of chronic hepatitis C after renal transplantation.

Adult↗

Clinical features and treatment outcome of idiopathic membranous nephropathy in Chinese patients.

We retrospectively studied the clinical course and treatment outcome of idiopathic membranous nephropathy (IMN) amongst 38 Chinese patients (25 male, 13 female, age 51.6 +/- 14.6 years, follow-up duration 58.2 +/- 51.1 months) who presented over a 10-year review period. Eight never received any form of specific treatment (group I), seven received oral corticosteroid alone for 6-9 months (group II), 17 were given corticosteroid plus cyclophosphamide for 6-12 months (group III), and six were treated with methylprednisolone alternating with chlorambucil every other month for 6 months (group IV). No untoward effect from drugs sufficient to alter the dosage used was recorded. After 6 months of treatment, over 50% of patients went into remission: a significant reduction in proteinuria (p = 0.01, 0.01, 0.02) with a corresponding rise in serum albumin levels (p = 0.01, 0.01, 0.04) was observed in groups II, III, and IV, respectively, but not in group I. During follow-up, one patient in each of groups I, III, IV, and two of group II developed renal function deterioration, which correlated with an abnormal presenting serum creatinine. In six group I and eight group III patients who have been followed for at least 5 years, there was progressive reduction in proteinuria in group III (p < 0.05), but not in group I: serum creatinine has remained unchanged in both groups. IMN runs a benign course in Chinese patients in Hong Kong, with 2.6% of patients going into end-stage renal failure during the study period. Contrary to reports in Caucasians, there is similar treatment response to steroid alone or a combination of steroid and cytotoxic agents.

Aged↗

Osteopenia in young hypogonadal women with systemic lupus erythematosus receiving chronic steroid therapy: a randomized controlled trial comparing calcitriol and hormonal replacement therapy.

OBJECTIVE: To evaluate the efficacy of calcitriol and hormonal replacement therapy (HRT) in the treatment of steroid-induced osteoporosis in hypogonadal women. METHODS: We studied 28 young patients (aged 37 +/- 6 yr) with systemic lupus erythematosus (SLE) on chronic steroid therapy for 130 +/- 22 months and requiring more than 10 mg/day prednisone. They were amenorrhoeic for more than 2 yr with proven ovarian failure. All had osteopenia with a T score at L2-4 of less than -1. They were randomized to receive HRT (conjugated oestrogen 0.625 mg daily from day 1 to day 21 plus medroxyprogesterone acetate 5 mg daily days 10-21) or calcitriol 0.5 microg daily. All received calcium carbonate 1 g/day. RESULTS: There were no differences in the baseline demographic, bone mineral density (BMD) and biochemical data between the two groups. Lumbar spine BMD increased by 2.0 +/- 0.4% after 2 yr with HRT (P<0.05), but reduced by 1.74 +/- 0.4% (P<0.05) with calcitriol treatment. No change was seen at the distal one-third radius with HRT treatment but significant bone loss (2.3 +/- 1.4%, P<0.02) was observed with calcitriol therapy. BMD at the hip did not change in both groups. Comparing both treatment groups, significant differences in the BMD at the spine (P<0.03) and radius (P<0.05) were seen at the end of 2 yr. The changes in urinary n-telopeptide excretion but not serum osteocalcin at 6 months and 12 months were inversely correlated with the changes in lumbar spine BMD at 24 months. HRT did not cause an adverse effect on SLE disease activity. CONCLUSION: HRT but not calcitriol could prevent bone loss in young hypogonadal women on chronic steroid therapy.

Adult↗