Primary calcified gastrinoma of the liver.
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Adult↗
Biomedical subjects
S L Tsai
Publications and source records attributed to S L Tsai.
Soluble Fas modulates interferon responsiveness.
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Apoptosis↗
A comparison of effectiveness and cost between two models of care for individuals with schizophrenia living in Taiwan.
Schizophrenia is a chronic disease that places tremendous costs and burden on patients, families, and communities. The purpose of this study was to compare the cost and effectiveness of a hospital-based home care model and a traditional community care model for schizophrenia in Taiwan using six principles of cost-effectiveness analysis. Based on the health care provider's analytic perspective, four effectiveness indicators and four service costs were identified and measured, and the ratio of average cost value to effectiveness score for each patient was calculated. According to that ratio, the hospital-based home care model was more cost-effective. The results suggest that the hospital-based outreach home care model is a cost-effective way to care for patients and their family in the community.
Adult↗
Apoptosis in viral hepatitis B and C.
Tumor necrosis factor (TNF) and TNF receptors (TNFR) are members of the growing TNF ligand and receptor families known to be involved in apoptosis, viral pathogenesis and immune regulation. The present report will focus on the role of apoptosis in the pathogenesis of viral hepatitis B and C. Although TNF was reported years ago to modulate viral infections, recent findings on the molecular pathways involved in TNFR signaling have allowed a better understanding of the molecular interactions between cellular and viral factors within the infected cell. The interactions of viral proteins with intracellular components downstream of the TNFR have highlighted at the molecular level that viruses can manipulate the cellular machinery to escape the immune surveillance and to favor spread infection. We will review here the mechanism of apoptosis and the role of viral proteins that regulate apoptosis in viral hepatitis B and C.
Apoptosis↗
Constitutive activation of nuclear factor kappaB in hepatocellular carcinoma.
BACKGROUND: Nuclear factor kappaB (NF-kappaB) is a transcription factor that plays important roles in cell proliferation and in immunity against viral infections. NF-kappaB is a dimer of Rel proteins that is sequestered in the cytoplasm as an inactive form through interaction with an inhibitory kappaB (IkappaB) protein. When IkappaB is degraded, the NF-kappaB dimer will enter the nucleus to activate the target genes. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection may activate NF-kappaB and, thus, may modulate cell apoptosis and may be associated with oncogenesis. The role of NF-kappaB in hepatocellular carcinoma (HCC) has not yet been explored. METHODS: Immunohistochemical staining to search for active nuclear RelA and nuclear IkappaBalpha proteins were done on formalin fixed liver tissues from 65 patients with HCC and from 9 normal control participants. Nuclear extracts of fresh-frozen tumor and nontumor liver tissues from 37 patients with HCC and from 7 normal controls were tested for NF-kappaB-DNA binding activity by electrophoretic mobility shift assay. The RelA and IkappaBalpha protein expressions were studied by Western blot analysis. RESULTS: Nuclear NF-kappaB stainings were significantly more abundant in HBV-infected or HCV-infected tumors as well as nontumor parts of HCC compared with normal controls. Nuclear NF-kappaB DNA binding activity and nuclear RelA protein expression were greater in tumor tissue compared with nontumor tissue, whereas cytosolic IkappaBalphs protein expression was generally greater in nontumor tissue compared with tumor tissue. CONCLUSIONS: Constitutive activation of NF-kappaB was found more frequently in tumor tissue compared with nontumor tissue. It is possible that NF-kappaB overexpression accompanied by dysregulation of IkappaBalpha may play a role in the hepatocarcinogenesis of HBV or HCV infection.
Adult↗
Activation of nuclear factor kappaB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis.
The hepatitis C virus (HCV) core protein is a multifunctional protein. It may bind to the death domain of tumor necrosis factor receptor 1 (TNFR1) and to the cytoplasmic tail of lymphotoxin-beta receptor, implying that it may be involved in the apoptosis and anti-apoptosis signaling pathways. In vitro studies have been inconclusive regarding its ability to inhibit or enhance TNF-alpha-induced apoptosis. To address this issue, electrophoretic mobility shift assay (EMSA) and immunohistochemical studies were used to show the activation of nuclear factor kappaB (NF-kappaB) in HCV-infected liver tissues and in HCV core-transfected cells. The activation of NF-kappaB was correlated with the apoptosis assays. The results showed that NF-kappaB activation could be shown in HCV-infected livers and HCV core-transfected cells. The data of EMSA correlated with those of immunohistochemical studies, which revealed a higher frequency of NF-kappaB nuclear staining in HCV-infected than in normal livers. NF-kappaB activation conferred resistance to TNF-alpha-induced apoptosis in HCV core-transfected cells. Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate sensitized them to TNF-alpha-induced apoptosis. These findings suggest that HCV infection may cause anti-apoptosis by activation of NF-kappaB and implicate a mechanism by which HCV may evade the host's immune surveillance leading to viral persistence and possibly to hepatocarcinogenesis.
Adult↗
Nurses' participation and utilization of research in the Republic of China.
A survey was done to improve understanding of nurses' participation in research activities and their utilization of research for practice in one developing country, the Republic of China. The sample for this 1996-1997 study was 382 staff nurses and nurse managers. Using two instruments designed for the project it was found that although research participation was low overall, 64% participated in some research activities with data collection and presentation at national conferences the most frequent activities. Nearly half the nurses had utilized research to change practice in the previous three years. The main barriers to utilization were lack of time and lack of staff. Role models, consultation and guidance to locate useful research were the main types of needed assistance. The findings provide direction for future training, education and managerial policy, especially for nurses in developing countries, which account for 84% of the world's population and 93% of the worldwide burden of disease.
Adult↗
Assessment of intragastric pH value changes after early nasogastric feeding.
Studies have suggested that early feeding after injury decreases morbidity and mortality. Few reports, however, have focused on the change in pH inside the stomach after early tube feeding. The aim of the present study was the assessment of 1) the change in intragastric pH after surgery, and 2) the effect of early nasogastric tube feeding on intragastric pH value. From April 1997 to February 1998, 80 patients who underwent colon resection for colorectal cancer by a single surgeon entered the study and were randomized into four groups. Twenty patients (group I) were kept on NPO for 1 wk, and 20 patients per group (groups II, III, and IV) were fed through a nasogastric tube from the second to the seventh postoperative day with low-residual (Osmolite HN), high-fat (Pulmocare), and glutamine-containing (AlitraQ) enteral formulas. Feeding started at 500 kcal/500 cc/d. If the patient tolerated the formula well, feeding increased to 1500 kcal/1500 cc(-1)/d(-1) the following day. Intragastric pH was measured preoperatively and then twice daily until the sixth postoperative day. The pH value of intragastric juice increased significantly once feeding started (3. 67 +/- 1.33 on the third postoperative day; 4.28 +/- 1.26 on the six postoperative day). The pH value seemed only mildly affected by the patient's tolerance for tube feeding (poorly tolerated group, pH 3. 52 +/- 1.75 versus 3.75 +/- 1.21 in the well-tolerated group on the third postoperative day; poorly tolerated group, pH 3.67 +/- 1.02 versus 4.45 +/- 1.27 in the well-tolerated group on the sixth postoperative day). The pH value of intragastric juice was higher in group II than in groups III and IV (4.51 +/- 1.57, 3.90 +/- 1.20, 4. 42 +/- 0.89 respectively, on the sixth postoperative day). This series suggests that early nasogastric feeding can significantly elevate the intragastric pH value in patients after resection of colorectal cancer. Nasogastric feeding may decrease the incidence of stress ulceration by elevating the pH value of intragastric juice.
Carbohydrates↗
Priority-setting for nursing research in the Republic of China.
The question of how public funds for research should be allocated has led to participatory priority-setting in prosperous democracies like Taiwan, Republic of China. Useful criteria for research priorities are scientific merit, social benefit and feasibility. Taking a health needs approach and using these criteria, nearly 200 nurses from service and education in a national forum participated in describing research priorities. Through the group method of idea-writing, for clinical nursing, of high priority were assessing quality, care of the elderly, and preventing infectious disease. For nursing education, research addressing advanced role preparation and bridging nursing education and practice were priorities. For nursing management, research of highest priority pertained to economic evaluation, personnel administration, and effectiveness. These suggestions from the deliberation of a committed group of nurses can help shape future national decisions about research funding and training.
Clinical Nursing Research↗
Prednisolone priming enhances Th1 response and efficacy of subsequent lamivudine therapy in patients with chronic hepatitis B.
Asian lamivudine trial has shown that hepatitis B e antigen (HBeAg) seroconversion rate during 1 year of lamivudine therapy was only 16% but was 64% in the subgroup of patients with a pretherapy serum alanine transaminase (ALT) level over 5 times the upper limit of normal (ULN). To test whether ALT rebound following corticosteroid priming enhances response to lamivudine therapy, a pilot study was conducted in 30 patients with ALT levels less than 5x ULN (43-169; N < 36 U/L). They received 30 mg of prednisolone daily for 3 weeks, 15 mg daily for 1 week, no treatment for 2 weeks, and then 150 mg of lamivudine daily for 9 months. Complete response (CR) was defined as ALT normalization with HBV-DNA seroclearance and HBeAg seroconversion. Peripheral blood mononuclear cell proliferation and cytokine secretion in response to recombinant HBV core antigen were serially assayed in 7 patients during priming and after withdrawal of prednisolone. Clinical rebound with an ALT over 5x ULN was observed in 20 patients (67%). Of these 20, 12 (60%) showed CR as compared with 1 (10%) of the 10 patients without significant ALT rebound (P <.002). The HBeAg seroconversion sustained in 70% of the patients 3 to 6 months after the end of lamivudine therapy. Immunological assays revealed that the responders showed Th1 dominant response and higher stimulation index to prednisolone priming. No serious side effect was encountered. These results suggest that corticosteroid priming induced immune/ALT rebound greatly enhances response to lamivudine therapy in chronic hepatitis B. Confirmation by randomized controlled trial is needed.
Adolescent↗
Impact of acute hepatitis B virus superinfection on chronic hepatitis C virus infection.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection is not uncommon, but the impact of acute HBV superinfection in patients with chronic HCV infection is still unknown. Two patients with well documented chronic HCV infection were hospitalized for acute hepatitis, which was serologically confirmed to be acute HBV superinfection. One patient who was seropositive for both HBV-DNA and HCV-RNA upon admission died of hepatic failure. The other became seronegative for HCV-RNA and recovered with alanine aminotransferase normalization, seroclearance of HBsAg, and antibodies to HCV. These findings confirm that acute superinfection in patients with chronic hepatitis may increase the risk for severe hepatitis, and suggest that HBV as the newcomer may suppress the pre-existing HCV. Together with the earlier observation that acute HCV superinfection suppresses pre-existing HBV, it seems that the timing or sequence of infection is a factor influencing the outcome of viral interactions.
Acute Disease↗
Identifying attitudinal barriers to family management of cancer pain in palliative care in Taiwan.
The purpose of this study was threefold: (1) to examine attitudes held by Taiwanese family caregivers of hospice inpatients with cancer that serve as barriers to cancer pain management; (2) to determine the relationship of attitudinal barriers to family caregiver hesitancy to report pain and to administer analgesics; and (3) to determine the relationship of attitudinal barriers to the adequacy of analgesics used by the patient. A total of 80 pairs of palliative care inpatients and their primary family caregivers participated in this study. Family caregivers completed the Barriers Questionnaire-Taiwan (BQT) form and a demographic questionnaire. The instruments completed by patients consisted of the Brief Pain Inventory-Chinese version and a demographic questionnaire. The data revealed that Taiwanese family caregivers of palliative care patients with advanced cancer had concerns about reporting pain and administering analgesics, particularly as they related to disease progression, side-effects and p.r.n. analgesics. Older and less-educated family caregivers scored significantly higher on the BQT than did their younger, more educated counterparts. Family caregivers' concerns measured by the BQT were related to family caregivers' reluctance to administer analgesics to their patients. Implications for a broader understanding of analgesics in the advancement of pain management in palliative care in Taiwan are discussed.
Adult↗
Ticlopidine-induced cholestatic hepatitis with anti-nuclear antibody in serum.
We describe a case of severe cholestatic hepatitis following administration of ticlopidine. A 57-year-old man without known liver disease developed jaundice approximately 3 weeks after initiation of ticlopidine for secondary prevention of stroke. Hyperbilirubinemia and abnormal liver function test values resolved 5 months after withdrawal of ticlopidine. The diagnosis of ticlopidine-induced cholestasis was made after thorough investigations had excluded other causes of jaundice. He was not retreated with ticlopidine. This case may serve to illustrate the possibility of ticlopidine hepatotoxicity, which has rarely been reported. Furthermore, to the best of our knowledge, ticlopidine-induced cholestatic hepatitis accompanied by autoantibody has not been previously reported. This case suggests that regular assessment of liver function should be performed in the initial 3 months of ticlopidine treatment due to the potential risk of adverse effects. In patients with abnormal biochemical test results, autoantibodies should be assessed.
Antibodies, Antinuclear↗
Acute exacerbation and hepatitis B virus clearance after emergence of YMDD motif mutation during lamivudine therapy.
Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication, but its long-term use may be associated with HBV tyrosine-methionine-aspartate-aspartate (YMDD) motif mutation. To examine the clinical features and course after emergence of YMDD mutants, 55 patients who received lamivudine therapy over 104 weeks at our unit were assayed for YMDD mutation(s). Thirty-two of them were found to have the YMDD mutation. They continued lamivudine therapy and were followed up weekly or biweekly if clinically indicated. Thirty (93.7%) of them showed elevation of alanine transaminase (ALT), and 13 (40.6%) experienced acute exacerbation at 4 to 94 weeks (median, 24 weeks) after emergence of the YMDD mutant. The incidence of exacerbation is much higher than 4.3% in patients without the YMDD mutation (P =.003). Compared with patients without exacerbation, patients with exacerbation had a significantly higher serum HBV-DNA level after emergence of the YMDD mutant (P <.005). Before exacerbation, serum HBV-DNA level was rising to its peak, followed by the peaking of ALT (247-2,010 U/L) 1 to 4 weeks later. Three patients developed hepatic decompensation, but then in association with hepatitis B e antigen (HBeAg) seroconversion, recovered. Of the 12 evaluable patients, 8 (75%) showed HBeAg seroconversion, and 3 showed mutant clearance within 1 to 5 months after exacerbation. In contrast, none of the patients without exacerbation showed HBeAg seroconversion (P <.001). These results indicate that acute exacerbations may occur after emergence of the YMDD mutation. The incidence, clinicopathological features, and subsequent course, and possibly the underlying immune mechanisms, are similar to those of wild-type HBV chronic infection. Because severe hepatitis may occur, patients should be followed carefully once the YMDD mutant emerges.
Adolescent↗
Prevalence and significance of thyroid autoantibodies in patients with chronic hepatitis C virus infection: a prospective controlled study.
OBJECTIVE: To clarify controversies on the prevalence and clinical significance of thyroid autoimmunity in hepatitis C virus (HCV) infection. DESIGN: A prospective controlled and follow-up study. PATIENTS AND MEASUREMENTS: Serum thyroid microsomal antibody (TMA) and thyroid stimulating hormone were assayed and compared in a consecutive, unselected series of 130 patients with chronic HCV infection, 130 sex/age (+/- 2 years)-matched patients with chronic hepatitis B virus (HBV) infection and 260 matched normal controls. RESULTS: The prevalence of thyroid autoantibodies in male patients with chronic HCV was < 2%. The prevalence of TMA (< 1:400) in female patients with chronic HCV infection was significantly higher than that of HBV controls (22.1 vs. 1.6%; P < 0.001), and higher but not significant compared with normal controls (13.5%). However, the trend of increasing prevalence with age in normal controls was not observed in HCV patients. TMA seropositive female HCV patients were not different from seronegative counterparts in age, duration of infection, HLA haplotype, associated autoantibodies and liver histology but had a significantly higher prevalence of genotype 1b/2b mixed infection (P < 0.01) and anti-GOR (P < 0.05). Of the 23 HCV patients seropositive for thyroid autoantibodies, seven had Hashimoto's thyroiditis, two had Graves' disease and three had received subtotal thyroidectomy. During follow-up, four of 15 female patients showed a 14-16-fold increase in TMA titre and one developed hyperthyroidism. Patients with thyroid autoantibodies did not show a propensity to develop thyroid dysfunction during interferon therapy. CONCLUSIONS: These results suggest a weak association between HCV and thyroid autoimmunity in females. As in the ordinary population with thyroid autoantibodies, they should be evaluated for thyroid status and be followed-up if thyroid autoimmunity is evident. However, seropositivity of thyroid autoantibodies is not a contraindication to interferon therapy.
Adult↗
Immunopathogenesis of viral hepatitis B and C.
Considerable evidence suggests that immune mechanisms are involved in the pathogenesis of both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Both class I-restricted CD8+ T cell and class II-restricted CD4+ T cell responses to viral antigens are important mechanisms that may be responsible for the hepatocyte damage in hepatitis B and C. CD4+ T cell proliferative responses to hepatitis B core antigen (HBcAg) in terms of stimulation index are correlated with hepatitis activity. These responses can be demonstrated in both adult and pediatric patients, and are more vigorous in patients with acute self-limited hepatitis B than in patients with chronic hepatitis B. Patients with hepatitis C also have a significant CD4+ T cell response to HCV antigens. These responses are also more vigorous in acute hepatitis C patients who recover than in patients who evolve to chronic hepatitis. In terms of major histocompatibility complexes (MHC) class I-restricted, CD8+ cytotoxic T lymphocyte (CTL) response, antigenic peptides derived from HBcAg, hepatitis B surface antigen (HBsAg), and polymerase have been demonstrated to be the targets for CTL recognition in hepatitis B patients. Multiple CTL epitopes within HBsAg, HBcAg and polymerase can be detected by sensitizing target cells with synthetic peptides. Likewise, multispecific, HCV-specific CTL responses can coexist with an extensive quasispecies of viral variants. The mechanisms of viral persistence in both hepatitis B and C remain to be clarified.
Hepatitis B↗
A synchrotron radiation beam-position monitor at the Taiwan Light Source.
A prototype photon-beam-position monitor has been designed, fabricated and tested at the Taiwan Light Source of the Synchrotron Radiation Research Center. Aluminium was chosen as the material of the blade electrodes due to its low atomic number and high thermal conductivity. The resolution of this photon-beam-position monitor was <+/-1 micro m. The sensitivity of the blade electrode has been measured in situ. Results of measurements for bending-magnet light and undulator light with different gaps are described.
Journal Article↗
Hepatitis C virus variants circumventing cytotoxic T lymphocyte activity as a mechanism of chronicity.
BACKGROUND & AIMS: High rate of chronicity after acute hepatitis C virus (HCV) infection cannot be explained in the presence of a multispecific cytotoxic T lymphocyte (CTL) response. The aim of this study was to investigate the effect of virus variants on CTL activity in patients in whom chronicity developed. METHODS: CTL clones specific to a decapeptide epitope derived from hypervariable region 1 were generated from 5 HLA-A2-positive patients with acute hepatitis C by in vitro stimulation with synthetic peptides. The sequential change of this CTL epitope and its influence on the CTL recognition were examined. RESULTS: Virus variants did not appear in 3 patients with recovery, whereas variants with altered peptide ligands capable of antagonizing CTL activity emerged rapidly in the remaining 2 patients in whom chronicity developed. Importantly, these HLA-A2-restricted, hypervariable region 1-specific CTL clones shared the use of T-cell receptor (TCR) genes AV6 and BV17. CONCLUSIONS: These data suggest that there is only a narrow T-cell repertoire responding to a single viral peptide/HLA ligand. The emergence of HCV variants with altered peptide ligands as TCR antagonists accompanied by a limited TCR repertoire may provide a mechanism for HCV chronicity.
Acute Disease↗