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Biomedical subjects

C-H Chen

Publications and source records attributed to C-H Chen.

At least 19 recordsLinked to original sources

The validity of in vitro ultrasonographic grading of osteoarthritic femoral condylar cartilage--a comparison with histologic grading.

OBJECTIVE: To establish an ultrasonographic grading for semi-quantitative evaluation of the femoral condylar cartilage of knee osteoarthritis (OA), in vitro, and compare the ultrasonographic grading with the histologic grading. DESIGN: Thirty-four patients going to receive total knee arthroplasty because of OA of the knee were recruited. Specimens of the distal medial and lateral femoral condyles were taken during the operation. The anterior and middle areas of the articular cartilage in each specimen were graded by in vitro ultrasonography (US) examination and histologic evaluation. The correlation between the US and histologic findings was analyzed. RESULTS: Sixty-seven specimens were collected. Both US and histologic changes were graded from I to IV. The correlation between the grading of US and histology was good in both anterior and middle areas (Rho=0.78, 0.89, P<0.001). The correlation between US grading over anterior area and histology grading over middle area was moderate (Rho=0.70, P<0.001). CONCLUSIONS: The moderate correlation between in vitro US and histology might permit quantitative in vivo assessment of cartilage.

Cartilage, Articular↗

Exposure of monomolecular lithographic patterns to ambient: an X-ray photoemission spectromicroscopy study.

Patterned self-assembled monolayers (SAMs) of alkanethiolates (AT) on Au and Ag substrates were imaged and characterized by scanning photoelectron microscopy (SPEM). The patterns were prepared in situ by direct writing with the zone-plate-focused X-ray beam provided by the SPEM station. Whereas both AT/Au and AT/Ag behaved alike upon the irradiation, which resulted in similar contrasts in the fabricated patterns and similar microspot spectra from the irradiated areas, the intensity relationship between the patterned and nonpatterned areas changed by different pathways for the Au and Ag substrates after the exposure of the patterns to ambient. The SPEM data imply that weakly bound molecular fragments are desorbed from the irradiated areas upon air exposure in the case of Ag, whereas adsorption of airborne molecules from ambient occurs for the Au substrate. The origin of the observed differences is presumably related to the specific branching patterns of irradiation-induced modification of AT/Au and AT/Ag.

Journal Article↗

Long-term inhibition of hepatitis B virus in transgenic mice by double-stranded adeno-associated virus 8-delivered short hairpin RNA.

RNA interference (RNAi) was reported to block hepatitis B virus (HBV) gene expression and replication in vitro and in vivo. However, it remains a technical challenge for RNAi-based therapy to achieve long-term and complete inhibition effects in chronic HBV infection, which presumably requires more extensive and uniform transduction of the whole infected hepatocytes. To increase the in vivo transfection efficiency in liver, we used a double-stranded adeno-associated virus 8-pseudotyped vector (dsAAV2/8) to deliver shRNA. HBV transgenic mice were used as an animal model to evaluate the inhibition effects of the RNAi-based gene therapy. A single administration of dsAAV2/8 vector, carrying HBV-specific shRNA, effectively suppressed the steady level of HBV protein, mRNA and replicative DNA in liver of HBV transgenic mice, leading to up to 2-3 log(10) decrease in HBV load in the circulation. Significant HBV suppression sustained for at least 120 days after vector administration. The therapeutic effect of shRNA was target sequence dependent and did not involve activation of interferon. These results underscore the potential for developing RNAi-based therapy by dsAAV2/8 vector to treat HBV chronic infection, and possibly other persistent liver infections as well.

Animals↗

Programmed cell death induced by Japanese encephalitis virus YL vaccine strain or its recombinant envelope protein in varied cultured cells.

OBJECTIVE: The Japanese encephalitis virus YL vaccine strain (JEV-YL) was investigated as regards its organ tropism and the role of recombinant envelope glycoprotein in the induction of apoptosis was explored. METHODS: Threevaried cell lines (HepG2, Vero and C6) were infected with JEV-YL or transfected with eukaryotic expression plasmids (pcE, pcF1R2, pcF1R1 and pcF2R2) which contain different parts of the envelope gene and phenotypic properties were examined by flow cytometry and DNA fragmentation analysis. RESULTS: After JEV-YL infection, smaller plaque was produced on HepG2 cells than on Vero cells, whereas no cytopathic effect was observed on C6 cells; moreover, by apoptosis and DNA fragmentation assays, the hallmark cytopathic effects were detected in HepG2 and Vero cells but not in C6 cells. Furthermore, cells used in our study transfected with recombinant core plasmid, pcE, which include full-length E gene but the deleted forms (pcF1R2, pcF1R1 and pcF2R2) did not have similar results as JEV-YLs. CONCLUSIONS: The JEV-YL vaccine strain had changed cell tropism to liver cells different from other virulent strains which have neural tropism, and in this study we proved that the transient-expressed entire E protein of JEV-YL could induce apoptosis and the mutations of E protein may change the organ tropism of JEV-YL.

Animals↗

The application of mini-implants for orthodontic anchorage.

The aim of this study was to explore the use of mini-implants for skeletal anchorage, and to assess their stability and the causes of failure. Forty-five mini-implants were used in orthodontic treatment. The diameter of the implants was 2mm, and their lengths were 8, 10, 12 and 14mm. The drill procedure was directly through the cortical bone without any incision or flap operation. Two weeks later, a force of 100-200g was applied by an elastometric chain or NiTi coil spring. Risk factors for the failure of mini-implants were examined statistically using the Chi-square or Fisher exact test as applicable. The average placement time of a mini-implant was about 10-15min. Four mini-implants loosened after orthodontic force loading. The overall success rate was 91.1%. The location of the implant was the significant factor related to failure. In conclusion, the mini-implants are easy to insert for skeletal anchorage and could be successful in the control of tooth movement.

Adult↗

Isoflurane preconditioning-induced cardio-protection in patients undergoing coronary artery bypass grafting.

BACKGROUND AND OBJECTIVES: Ischaemic preconditioning is commonly regarded as one of the most powerful protective mechanisms against a subsequent lethal ischaemic injury during coronary artery bypass graft surgery but is not practiced routinely. Experimentally, isoflurane, a commonly used volatile anaesthetic agent, provides myocardial protection through a signal transduction cascade that is remarkably similar to the pathways identified in ischaemic preconditioning. The aim of our study was to investigate whether pre-ischaemic administration of isoflurane exerted protection against prolonged ischaemia with functional recovery and reduced necrosis among patients undergoing coronary artery bypass graft surgery. METHODS: Forty patients scheduled for elective coronary artery bypass graft operations were prospectively randomized into the control or isoflurane groups. In the isoflurane group, isoflurane 2.5 minimum alveolar concentration was administered for 15 min followed by a 5-min washout period before aortic cross-clamping. The control group received a time-matched period of isoflurane-free cardiopulmonary bypass. The conduction of anaesthesia and surgery were standardized in all patients. Haemodynamic data, troponin I release and inotropic support were measured and recorded perioperatively. RESULTS: There were no adverse effects related to isoflurane administration. In the isoflurane group, the mean cardiac index after cardiopulmonary bypass was significantly higher than the pre-bypass value (P < 0.05), whereas no difference was found in the control group. At 15 min after cardiopulmonary bypass and 6 h after surgery, the changes in cardiac index and stroke volume index were significantly higher in the isoflurane group than in the control group (P < 0.05). There was a consistently lower release of troponin I in the isoflurane group compared to the control group. Compared to the controls, the mean troponin I level was significantly reduced in the isoflurane group at 24 h after surgery (P = 0.042). CONCLUSIONS: The present results support the preconditioning effect of isoflurane in patients undergoing coronary artery bypass graft surgery as clinically feasible and providing optimal cardiac protection.

Aged↗

Survival benefit of transcatheter arterial chemoembolization in patients with hepatocellular carcinoma larger than 10 cm in diameter.

BACKGROUND: The safety and survival benefit of transcatheter arterial chemoembolization for patients with huge hepatocellular carcinoma is uncertain. AIM: To evaluate the role of embolization in unresectable hepatocellular carcinomas larger than 10 cm. METHODS: Twenty-six consecutive patients who had an unresectable hepatocellular carcinoma larger than 10 cm and refused aggressive treatment, were enrolled as the control group. Another 31 patients matching with the control cases and undergoing embolization for huge unresectable hepatocellular carcinoma served as the embolization group. Survival between the two groups was compared. RESULTS: Two patients (7%) died from embolization-related complications. Patients in embolization group had longer survival than those in control group (median survival: 9.13 vs. 2.1 months). The 1-, 3- and 5-year survival rates in embolization group were 42%, 13% and 7% respectively. The 1- and 3-year survival rates for patients in control group were 8% and 0% respectively. In multivariate analysis, embolization and prothrombin ratio < or =1.2 were two independent factors associated with a better survival. CONCLUSIONS: Embolization-related mortality is low for huge hepatocellular carcinoma, and the technique provides survival benefit in patients with unresectable hepatocellular carcinomas larger than 10 cm in diameter.

Adult↗

Soft-tissue metastasis of osteosarcoma to the submental vestibule.

A case of metastatic osteosarcoma in the submental vestibule of the oral cavity and the lung is described in an 18-year-old male with primary osteosarcoma occurring in the sacrum. Dissemination of osteosarcoma to other organs, especially early to the lung, is common, but its metastasis to the oral mucosa has been rarely reported. The patient presented 6 years after initial diagnosis, suggesting the need for careful long-term follow-up of patients with osteosarcoma. This case also illustrates that immunohistochemical staining of osteocalcin is useful to confirm the histological diagnosis of oral soft-tissue metastasis.

Adolescent↗

Fully automated large-scale assessment of visceral and subcutaneous abdominal adipose tissue by magnetic resonance imaging.

OBJECTIVE: To describe and evaluate a fully automated method for characterizing abdominal adipose tissue from magnetic resonance (MR) transverse body scans. METHODS: Four MR pulse sequences were applied: SE, FLAIR, STIR, and FRFSE. On 39 subjects, each abdomen was traversed by 15 contiguous transaxial images. The total abdominal adipose tissue (TAAT) was calculated from thresholds obtained by slice histogram analysis. The same thresholds were also used in the manual volume calculation of TAAT, subcutaneous abdominal adipose tissue (SAAT) and visceral abdominal adipose tissue (VAAT). Image segmentation methods, including edge detection, mathematical morphology, and knowledge-based curve fitting, were used to automatically separate SAAT from VAAT in various 'nonstandard' cases such as those with heterogeneous magnetic fields and movement artefacts. RESULTS: The percentage root mean squared errors of the method for SAAT and VAAT ranged from 1.0 to 2.7% for the four sequences. It took approximately 7 and 15 min to complete the 15-slice volume estimation of the three adipose tissue classes using automated and manual methods, respectively. CONCLUSION: The results demonstrate that the proposed method is robust and accurate. Although the separation of SAAT and VAAT is not always perfect, this method could be especially helpful in dealing with large amounts of data such as in epidemiological studies.

Abdominal Fat↗

Decision threshold adjustment in class prediction.

Standard classification algorithms are generally designed to maximize the number of correct predictions (concordance). The criterion of maximizing the concordance may not be appropriate in certain applications. In practice, some applications may emphasize high sensitivity (e.g., clinical diagnostic tests) and others may emphasize high specificity (e.g., epidemiology screening studies). This paper considers effects of the decision threshold on sensitivity, specificity, and concordance for four classification methods: logistic regression, classification tree, Fisher's linear discriminant analysis, and a weighted k-nearest neighbor. We investigated the use of decision threshold adjustment to improve performance of either sensitivity or specificity of a classifier under specific conditions. We conducted a Monte Carlo simulation showing that as the decision threshold increases, the sensitivity decreases and the specificity increases; but, the concordance values in an interval around the maximum concordance are similar. For specified sensitivity and specificity levels, an optimal decision threshold might be determined in an interval around the maximum concordance that meets the specified requirement. Three example data sets were analyzed for illustrations.

Algorithms↗

Genital porokeratosis: a series of 10 patients and review of the literature.

BACKGROUND: Porokeratosis (PK) is an uncommon disorder of epidermal keratinization with a unique clinical appearance, unknown aetiology, and an unpredictable outcome. Genital PK (defined as localized PK confined to the genital area in this study) is extremely rare and is not well documented. OBJECTIVES: To evaluate the clinical manifestations, histopathology, clinical course and treatment response for genital PK. METHODS: We reviewed the clinicohistological data from 10 patients with genital PK seen at Chang Gung Memorial Hospital from 1990 to 2005. RESULTS: Seven patients had lesions only in the genital area, and three patients had genital and adjacent areas involved. All patients were male and the mean age at initial diagnosis was 46.0 years (range 36-59). All but one patient presented with pruritic lesions. Three patients (30%) had diabetes mellitus. No malignant transformation was observed. Surgical excision was the most effective treatment if it could be performed. CONCLUSIONS: Genital PK appeared more frequently in the Asian population than in reports from western countries. Genital PK presented mostly as pruritic lesions in Taiwan, with a wide age distribution. Long-term follow-up might be needed.

Adult↗

Long-term effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis.

We assessed the efficacy of interferon (IFN) alpha-2b plus ribavirin therapy in patients with hepatitis C virus (HCV)-related cirrhosis, and elucidated the risk factors for the development of hepatocellular carcinoma (HCC) to determine whether these therapies might reduce the incidence of HCC. One hundred and thirty-two HCV-cirrhotic patients receiving IFN alpha-2b (3 or 5 MU thrice weekly) and oral ribavirin (1,000-1,200 mg/day) for 24 or 48 weeks were analysed. Cumulative incidence of HCC was estimated by the Kaplan-Meier method. The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log-rank test and by multivariate Cox's regression analysis. A total of 116 patients completed the treatment and 73 (55%) achieved a sustained virological response (SVR). Stepwise logistic regression analysis showed that nongenotype 1b (P < 0.001) and low viral load (P = 0.018) were independent variables of SVR. During a median follow-up period of 37 (12-63) months, HCC developed in 11 patients with non-SVR and five with SVR (P = 0.0178), whereas there was no difference between those with transient biochemical response and nonresponse (P = 0.5970). The Kaplan-Meier method also showed that old age (>or=60 years) (P = 0.0034) and genotype 1b (P = 0.0104) were associated with HCC occurrence. Using Cox's regression analysis, non-SVR (odds ratio = 3.521, P = 0.036), male (odds ratio = 6.269, P = 0.011) and old age (odds ratio = 3.076, P = 0.049) were independent significant risk factors contributing to HCC development. Our results suggest that achieving SVR by IFN alpha-2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV-related cirrhosis.

Adult↗

Site-specific mutation of the interferon sensitivity-determining region (ISDR) modulates hepatitis C virus replication.

The number of amino acid substitutions in the interferon sensitivity-determining region (ISDR) in the nonstructural 5A (NS5A) gene of hepatitis C virus (HCV) is closely associated with the interferon (IFN) response and viral load. Several HCV replicon-based studies have reported that ISDR sequences had an influence on viral replication in vitro. However, it is unclear as to how different ISDR sequences affect HCV replication. Various clinically observed ISDR sequences were introduced into HCV replicons and their contribution to viral replication was investigated using a colony formation assay and/or a transient replication assay. A mapping study of the ISDR was performed to identify the amino acid positions that critically affect replication. While no colonies were formed in the colony formation assay using HCV replicons with few mutations (0, 1 and 3) in the ISDR, numerous colonies (>200) appeared when using constructs with six mutations. Introduction of various distinct ISDR sequences with multiple mutations resulted in replication enhancement in transient assays. A mapping study identified several specific sites in the ISDR that critically affected replication, including codon 2209 which, in patients, was closely associated with a strong response to IFN. ISDR sequences associated with a clinical IFN response and viral load modulated the replication of HCV replicons, suggesting the importance of the ISDR sequence in HCV infection.

Amino Acid Sequence↗

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↗

Effects of a calcineurin inhibitor, tacrolimus, on glutamate-dependent potentiation in pelvic-urethral reflex in anesthetized rats.

Effects of tacrolimus, a protein phosphatase 2B inhibitor, on the reflex plasticity between the pelvic afferent nerve fibers and the urethra were examined in urethane-anesthetized rats. Repetitive stimulation (1 Hz) induced a potentiation (0.9+/-0.2 and 10.5+/-1.6 spikes in control and repetitive stimulation groups, respectively, P<0.01, N=10) in the activities of the pelvic-urethral reflex. Intrathecal tacrolimus (0.1 mM, 10 microl, bolus) blocked repetitive stimulation-induced potentiation in pelvic-urethral reflex activities (3.2+/-0.9 spikes in tacrolimus group versus 10.5+/-1.6 spikes in repetitive stimulation group, P<0.01, N=10). Glutamate (intrathecal, 0.1 mM, 10 microl, bolus) and N-methyl-D-aspartic acid (intrathecal, 0.1 mM, 10 microl, bolus) both reversed the blocking effects exerted by tacrolimus on repetitive stimulation-induced pelvic-urethral reflex potentiation (15.0+/-1.4 spikes in glutamate group and 11.4+/-1.4 spikes in N-methyl-D-aspartic acid group versus 3.2+/-0.9 spikes in tacrolimus-treated repetitive stimulation group, P<0.01, N=7). In addition, the reversal effect elicited by these two agonists of glutamate receptors showed no statistical difference (P=NS, N=7). All these results demonstrated that tacrolimus could block glutamatergic N-methyl-D-aspartic acid receptor-mediated potentiation in pelvic-urethral reflex activities. This finding may be pathologically relevant in patients who take tacrolimus as immunosuppressant therapy. Whether tacrolimus will induce urine incontinence in such patients or not needs further investigation.

Anesthesia↗

Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in ankylosing spondylitis: MMP-3 is a reproducibly sensitive and specific biomarker of disease activity.

OBJECTIVE: To submit serum levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) to statistical analyses to test their exact degrees of clinical usefulness as biomarkers for detecting high disease activity in ankylosing spondylitis (AS), comparing them with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). METHODS: Serum levels of MMP-1, -3, -9 and TIMP-1 and -2 were measured in 42 AS patients and 20 healthy controls. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) provided the gold standard for measuring disease activity. Patients with BASDAI > or =4 were regarded as having high disease activity. The results were compared with results for a separate cohort of 41 AS patients. RESULTS: Only MMP-3 levels were significantly higher in AS patients than in healthy controls (P<0.001). Within AS patients, MMP-3 levels were also higher in patients with high disease activity compared with those with low disease activity, and correlated significantly with BASDAI (r = 0.366, P = 0.017) and functional indices (r = 0.344, P = 0.026). The correlation with BASDAI was stable in a 1-yr follow-up (r = 0.464, P = 0.095) and reproducible with two different enzyme-linked immunosorbent assays. For detecting high disease activity, the sensitivity and specificity of MMP-3 level was 69.2 and 68.8% respectively. Most importantly, using receiver operating characteristic plots to analyse the two cohorts, MMP-3 was more accurate than ESR and CRP in detecting AS patients with high disease activity (P = 0.01 and P = 0.009, respectively). CONCLUSION: Using several analytical approaches that have never been reported previously, we showed that MMP-3 is a more useful biomarker than ESR and CRP to detect high disease activity in AS.

Adult↗