PubMed Health⌕ Search

Biomedical subjects

W-C Lee

Publications and source records attributed to W-C Lee.

12 recordsLinked to original sources
PubMed2006

Mycobacterium tuberculosis infection following renal transplantation in Taiwan.

BACKGROUND: Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. Post-transplant (post-Tx) TB is a problem in successful long-term outcome of renal transplantation recipients. It is a life-threatening opportunistic infection that is frequently encountered, but the diagnosis is often delayed. With the emergence of newer potent immunosuppressive regimens and an increased incidence of TB in the general population, post-Tx TB among transplant recipients can be anticipated. Our objective was to describe the pattern and risk factors of TB infection, and the prognosis in an endemic area. METHODS: This study was a retrospective review of the records of 756 renal transplant recipients in our hospital during the period from January 1983 to December 2003. The demographic data, transplant characteristics, clinical manifestations, diagnostic criteria, treatment protocol, and long-term outcome of this cohort of patients were analyzed. RESULTS: Thirty-one episodes developed into TB in 29 patients (3.8%) with a mean age of 45.5 (range: 24.2-66.2) years and a mean post-Tx period of 57.9 (range: 1.2-145.2) months. The forms of the diseases were pulmonary in 22/31 (71%), disseminated in 1/31 (3%), miliary in 1/31 (3%), and extrapulmonary in 7/31 (23%). All patients initially received 4-drug combination therapy, and then dosage was adjusted based on clinical condition. Because of drug interaction, a mean 2-fold increase in the dose of calcineurium inhibitor, but no change in steroid, was required. Twenty-two patients (71%) had an elevated creatinine (Cr) level, and 6 (19%) patients did not recover owing to tissue-proof acute rejection (3 cases) and chronic allograft nephropathy (3 cases), respectively, after treatment. The serum Cr level on diagnosis of TB was 1.9+/-0.7 mg/dL; it then deteriorated to 2.4+/-1.5 mg/dL (P=0.134). Hepatotoxicity developed in 11 patients (35.5%) during treatment. Twenty-five patients were successfully treated, 2 patients remain under treatment, and 4 (12.9%) died. Based on univariate analysis, we found the post-Tx TB risk factors were diabetes and more than 3 episodes of rejection, modalities for acute rejection (high-dose steroid and anti-lymphocyte globulin), and maintenance therapy with steroid. CONCLUSION: Post-Tx TB is a serious problem worldwide, and a high index of suspicion is warranted to ensure early diagnosis and prompt initiation of treatment for TB among renal transplant patients. The use of optimal immunosuppressive agents to minimize acute rejection seems reasonable to prevent TB infection in endemic areas like Taiwan. More than 9 months of treatment may be necessary to prevent recurrence.

Adult↗
PubMed2004

Design, synthesis, and analysis of a polyethelene glycol-modified (PEGylated) small molecule inhibitor of integrin {alpha}4{beta}1 with improved pharmaceutical properties.

Integrin alpha4beta1 plays an important role in inflammatory processes by regulating the migration of leukocytes into inflamed tissues. Previously, we identified BIO5192 [2(S)-{[1-(3,5-dichloro-benzenesulfonyl)-pyrrolidine-2(S)-carbonyl]-amino}-4-[4-methyl-2(S)-(methyl-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetyl}-amino)-pentanoylamino]-butyric acid], a highly selective and potent (K(D) of 9 pM) small molecule inhibitor of alpha4beta1. Although BIO5192 is efficacious in various animal models of inflammatory disease, high doses and daily treatment of the compound are needed to achieve a therapeutic effect because of its relatively short serum half-life. To address this issue, polyethylene glycol modification (PEGylation) was used as an approach to improve systemic exposure. BIO5192 was PEGylated by a targeted approach in which derivatizable amino groups were incorporated into the molecule. Two sites were identified that could be modified, and from these, five PEGylated compounds were synthesized and characterized. One compound, 2a-PEG (K(D) of 19 pM), was selected for in vivo studies. The pharmacokinetic and pharmacodynamic properties of 2a-PEG were dramatically improved relative to the unmodified compound. The PEGylated compound was efficacious in a rat model of experimental autoimmune encephalomyelitis at a 30-fold lower molar dose than the parent compound and required only a once-a-week dosing regimen compared with a daily treatment for BIO5192. Compound 2a-PEG was highly selective for alpha4beta1. These studies demonstrate the feasibility of PEGylation of alpha4beta1-targeted small molecules with retention of activity in vitro and in vivo. 2a-PEG, and related compounds, will be valuable reagents for assessing alpha4beta1 biology and may provide a new therapeutic approach to treatment of human inflammatory diseases.

Animals↗
PubMed2003

An assessment of the mechanistic differences between two integrin alpha 4 beta 1 inhibitors, the monoclonal antibody TA-2 and the small molecule BIO5192, in rat experimental autoimmune encephalomyelitis.

Integrin alpha 4 beta 1 plays an important role in inflammatory processes by regulating the migration of lymphocytes into inflamed tissues. Here we evaluated the biochemical, pharmacological, and pharmacodynamic properties and efficacy in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, of two types of alpha 4 beta 1 inhibitors, the anti-rat alpha 4 monoclonal antibody TA-2 and the small molecule inhibitor BIO5192 [2(S)-[[1-(3,5-dichloro-benzenesulfonyl)-pyrrolidine-2(S)-carbonyl]-amino]-4-[4-methyl-2(S)-(methyl-[2-[4-(3-o-tolyl-ureido)-phenyl]-acetyl]-amino)-pentanoylamino]-butyric acid]. TA-2 has been extensively studied in rats and provides a benchmark for assessing function. BIO5192 is a highly selective and potent (KD of <10 pM) inhibitor of alpha 4 beta 1. Dosing regimens were identified for both inhibitors, which provided full receptor occupancy during the duration of the study. Both inhibitors induced leukocytosis, an effect that was used as a pharmacodynamic marker of activity, and both were efficacious in the EAE model. Treatment with TA-2 caused a decrease in alpha 4 integrin expression on the cell surface, which resulted from internalization of alpha 4 integrin/TA-2 complexes. In contrast, BIO5192 did not modulate cell surface alpha 4 beta 1. Our results with BIO5192 indicate that alpha 4 beta 7 does not play a role in this model and that blockade of alpha 4 beta 1/ligand interactions without down-modulation is sufficient for efficacy in rat EAE. BIO5192 is highly selective and binds with high affinity to alpha 4 beta 1 from four of four species tested. These studies demonstrate that BIO5192, a novel, potent, and selective inhibitor of alpha 4 beta 1 integrin, will be a valuable reagent for assessing alpha 4 beta 1 biology and may provide a new therapeutic for treatment of human inflammatory diseases.

Animals↗
PubMed2003

Using affected sibling pairs to distinguish the direct effect of a susceptibility gene and the indirect effect of linkage disequilibrium.

A positive result for a transmission/disequilibrium test (TDT) can occur for two reasons: a) the allele itself is a cause of disease predisposition (direct effect); or b) the allele is in linkage disequilibrium with a disease-causing gene (indirect effect). A test was proposed based on affected sibling pairs (ASPs) to distinguish between the two. Simulation showed that the test has the correct type I error rate and favourable power (power >50% for 50 ASPs; >75% for 100 ASPs; >85% for 150 ASPs). Making this distinction is important for setting the direction for subsequent studies following a positive TDT result.

Alleles↗
PubMed2002

Estimation of prognosis after hepatectomy for hepatocellular carcinoma.

BACKGROUND: The preferred means of treatment for hepatocellular carcinoma is surgical resection. However, the tumour recurrence rate is high. Accurate estimation of the risk of tumour recurrence after hepatectomy may facilitate the administration of adjuvant therapy after hepatectomy to patients with a high likelihood of tumour recurrence. METHODS: The clinical and pathological profiles of 176 patients undergoing hepatectomy for hepatocellular carcinoma from March 1992 to August 1998 were reviewed. The Kaplan--Meier method and log rank test were used to analyse univariate prognostic factors. The Cox proportional hazard model was used for multivariate analysis. Disease-free and overall cumulative survival rates were estimated with respect to the number of prognostic factors. RESULTS: Independent factors associated with a lower disease-free survival included the presence of venous infiltration, presence of daughter tumours, absence of tumour encapsulation and tumour size exceeding 5 cm. Factors decreasing the overall survival rate included the presence of venous infiltration, absence of tumour encapsulation and surgical resection margin less than 1 cm. The 1-year disease-free survival rate decreased from 77.5(s.e. 5.6) to 14.0(8.5) per cent when the number of risk factors present increased from zero to three. The 5-year survival rate decreased from 60.2(11.7) per cent to zero when the number of risk factors increased from zero to three. CONCLUSION: The deterioration of disease-free or overall survival of patients with hepatocellular carcinoma after hepatectomy correlates with increasing number of risk factors. The number of risk factors can be employed to accurately estimate disease-free and overall survival.

Carcinoma, Hepatocellular↗
PubMed2002

Spontaneous tumour rupture and prognosis in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common disease in Taiwan. Ruptured HCC is an uncommon and potentially fatal complication of the condition. Information on the impact of ruptured HCC on hepatic resection is, however, limited. METHODS: The clinical features of 60 patients with ruptured HCC who underwent hepatic resection from 1986 to 1998 were reviewed. Clinical features and factors influencing the outcome of 475 patients with non-ruptured HCC were used for comparison. RESULTS: Of 535 surgically resected HCCs, 60 (11.2 per cent) were ruptured. Univariate analysis showed that sudden onset of abdominal pain, physical signs of haemodynamic unstability, reduced haemoglobin level and a raised aspartate aminotransferase level were more frequently found in patients with ruptured HCC than in those with non-ruptured tumours. Multivariate stepwise logistic regression analysis revealed sudden-onset abdominal pain to be the only independently significant factor in patients in the ruptured HCC group. The 1-, 3- and 5-year survival rates of patients with non-ruptured HCC were 72.1, 47.3 and 33.9 per cent, and those of patients with ruptured HCC were 54.2, 35.0 and 21.2 per cent respectively. Similar overall survival rates were found in patients with ruptured and non-ruptured HCC, although patients in the non-ruptured HCC group had a significantly better disease-free survival rate (P = 0.023). CONCLUSION: The presence of sudden-onset abdominal pain is the only independent indicator of ruptured HCC. Hepatic resection, when feasible, is the treatment of choice and can result in an overall survival rate comparable to that of patients with non-ruptured HCC.

Abdominal Pain↗
PubMed2002

Hepatic resection for hepatocellular carcinoma in Taiwan.

AIMS: We examined the clinical features and outcome of 80 patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection; 32 patients were under 30 years old (younger-HCC), and 48 patients were over 70 years (elderly-HCC). METHODS: Clinical features of 32 cases of younger-HCC (less than 30 years old) and 48 elderly-HCC (over 70 years old) were reviewed between 1986 and 1999. The clinical features, pathological findings and outcome of the younger and elderly HCC patients were summarized for comparison. RESULTS: Of 573 HCC patients who underwent hepatic resection, 32 were younger than 30 years old and 48 older than 70 years. Less hepatitis B infection, higher hepatitis C infection, more liver cirrhosis development, and a higher ICG 15min retention ratio than the younger group. The younger group tended to have a larger tumor size, more major hepatectomy, more operative blood loss during operation, more perioperative blood transfusion, and more recurrence when compared with the elderly-HCC group. The elderly-HCC group had a significantly better disease-free survival rate than the younger-HCC group. The younger-HCC group had a similar overall survival rate to the elderly-HCC group. CONCLUSIONS: These results seem to indicate a possible difference in the HCC carcinogenesis between younger and elderly patients. The overall survival of the younger HCC patients who undergone hepatic resection was as favorable as that of the elderly.

Adult↗
PubMedDate not supplied

Liver stellate cells suppress dendritic cells through IL-10.

Liver allografts can be spontaneously accepted across an MHC class I disparity, the mechanism of which is still not known. Since the liver has a large amount of immature dendritic cells, these elements may contribute to transplant acceptance. However, the reason why liver dendritic cells are immature status is unknown. In this study, bone marrow-derived dendritic cell progenitors were cocultured with liver stellate cells, which produce the immunosuppressive cytokines IL-10 and TGF-beta. The results revealed that dendritic cells cocultured with liver stellate cells express low levels of costimulatory molecules with decreased allostimulatory capacity. Addition of anti-IL-10 antibody to the culture media to neutralize IL-10 effects reversed the allostimulatory function of dendritic cells cocultured with stellate cells. In conclusion, liver dendritic cells are conditioned by stellate cells to maintain an immature status, which may contribute to the low immunity of liver. One of the mechanisms that stellate cells may influence dendritic cells is through IL-10.

Animals↗