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Biomedical subjects

C H Chen

Publications and source records attributed to C H Chen.

At least 109 records · Page 6Linked to original sources

Lamivudine is effective for the treatment of reactivation of hepatitis B virus and fulminant hepatic failure in renal transplant recipients.

Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. The aim of this study is to elucidate the effectiveness of lamivudine for the treatment of HBV reactivation with or without fulminant hepatic failure in renal transplant recipients. Forty-two renal transplant recipients (30 men, 12 women) were enrolled onto this study. Eight patients presented with HBV reactivation without fulminant hepatic failure and were administered lamivudine (group I), 5 patients presented with HBV and hepatic failure and were administered lamivudine (group II), 5 patients presented with HBV and hepatic failure but were not administered lamivudine (group III), and 24 patients were asymptomatic HBV carriers who were not administered lamivudine (group IV). Lamivudine was administered at a dose of 100 or 150 mg once daily. A greater prevalence of recent use of a combination of antilymphocyte immunoglobulin (ALG) and methylprednisolone (MP) occurred in patients with hepatic failure (groups II and III) than those without hepatic failure (30% versus 6.3%; P = 0.043). However, there was no significant difference in the incidence of MP use alone (20% versus 25%; P = 0.746). Mortality rates for groups I, II, and III were significantly different (12.5%, 40%, 100%; P = 0.008). One patient in group I died of sepsis without evidence of HBV DNA, even in the terminal event. In group II, 3 of 5 patients (60%) were rescued by lamivudine therapy. In group III, without lamivudine treatment, there was a 100% mortality rate despite intensive plasmapheresis. HBV DNA was not detectable after lamivudine treatment in 7 of 8 patients in group I and 3 of 5 patients in group II. Creatinine levels did not change significantly during lamivudine treatment. Hepatitis B surface antigen and hepatitis B e antigen seroconversion rates after lamivudine treatment were 7.7% and 37.5%, respectively. We conclude that ALG is a potent trigger of HBV-related fulminant hepatic failure in renal transplant recipients, whereas lamivudine is an effective and lifesaving treatment. Prompt use of lamivudine is recommended in renal transplant recipients with evidence of HBV reactivation to prevent catastrophic fulminant hepatic failure.

Adolescent↗

Lateral collateral ligament reconstruction using quadriceps tendon-patellar bone autograft with bioscrew fixation.

The lateral collateral ligament is the primary stabilizer against varus stress and is also an important contributor in maintaining posterolateral knee stability. Quadriceps tendon-patellar bone autograft has been used for anterior or posterior cruciate ligament reconstruction. We introduce a reconstructive procedure to restore the lateral collateral ligament using a quadriceps tendon-patellar bone autograft. The procedure is designed for unstable knees with concomitant cruciate ligament tear and posterolateral complex injury. This is a reasonable choice especially when allograft tissue is not available or in patients who are not suited for the use of bone-patellar tendon-bone autograft.

Arthroscopy↗

Assessment of cardiovascular dynamics by pressure-area relations in pediatric patients with congenital heart disease.

OBJECTIVES: It is particularly useful to separately quantify the ventricular contractility and loading conditions for a better understanding of the cardiovascular dynamics in congenital heart disease, where abnormalities in chamber and loading properties may coexist. Furthermore, ventricular contractility and loading conditions may alter independently or simultaneously with disease progression and therapeutic intervention. The objectives of the present study were (1) to test whether ventricular pressure-area analysis can provide such quantitation among patients with various forms of congenital heart disease, (2) to reveal basal cardiovascular interaction in congenital heart disease by means of pressure-area analysis, and (3) to test the feasibility of this method in a simplified and less invasive form to further enhance its clinical value. METHODS: We constructed pressure-area loops during caval occlusion by using transthoracic echocardiographic automated border detection combined with ventricular pressure recordings in 59 pediatric patients with congenital heart disease and in 7 normal control subjects. RESULTS: Area measurements obtained by automated border detection were highly reproducible, and area changes reflected volume changes. The pressure-area data provided load-independent measures of contractility, which were consistently increased by use of dobutamine (P <.05). End-systolic and arterial elastance individually quantified simultaneous changes in ventricular contractility and loading with milrinone infusion and predicted net cardiac performance. The pressure-area analysis better characterized the ventricular contractile states under a variety of loading conditions in congenital heart disease, whereas predominant load dependence of conventional indices confounded them. Furthermore, pressure-area relations were reasonably estimated from a single beat and from aortic pressure data during abdominal compression. CONCLUSIONS: Pressure-area analysis should provide a useful modality with which to assess cardiovascular dynamics in pediatric patients with congenital heart disease in more detail and should thus help improve the management of patients with this disease.

Adolescent↗

Aspirin differentially regulates endotoxin-induced IL-12 and TNF-alpha production in human dendritic cells.

OBJECTIVE: In the development of autoimmune diseases, dendritic cells (DC) play critical roles. Here, we examined the effect of aspirin on lipopolysaccharide (LPS)-induced DC activation. METHODS: The monocyte-derived DC were established. The cytokine production was measured by ELISA, reverse transcriptase/polymerase chain reaction, or intracellular staining analyzed by flow cytometry. The expression of cell surface molecules was determined by flow cytometry. RESULTS: Aspirin inhibited LPS-induced DC maturation and costimulatory molecules expression. Aspirin, at therapeutic concentrations, also decreased LPS-induced IL-12 and IL-10 production. In contrast, the LPS-induced TNF-alpha production was enhanced by aspirin. The differential effects of aspirin on IL-12 and TNF-alpha production may not be due to down-regulation of cyclooxygenase activities. CONCLUSION: The various effects of aspirin on LPS-stimulated DC may influence the understanding of the diverse immunomodulatory mechanisms of this anti-inflammatory drug.

Aspirin↗

Treatment of distal clavicle fracture using Kirschner wires and tension-band wires.

BACKGROUND: Nonunion frequently follows distal clavicle fracture. Traditional pinning methods using the through acromioclavicular articulation may result in osteoarthritic changes or ankylosis. This study introduces a direct pinning technique in which the acromioclavicular joint is spared. METHODS: Twelve patients with displaced distal clavicle fractures received open reduction and fixation with Kirschner wires (K-wires) and tension-band wires, from May 1996 to March 1997. The indication for surgery was type IIa fracture or fracture with displacement. Unrestricted passive and active range of motion was performed as soon as possible after the operation. Stretching and exertional exercises were permitted after radiographs showed an osseous union and after the implants were removed. RESULTS: Eleven patients achieved osseous union with painless full motion. Union time ranged from 3 to 6 months. One patient suffered from more comminuted fracture because of a fall 2 months after operation. This patient received a revision surgery with distal clavicle resection and coracoclavicle reconstruction. Symptomless ossification around the coracoclavicle ligament was noted on radiographs in one patient. The ossification did not progress after the 9-month follow-up. CONCLUSION: Edwards reported a rate of 45% delayed union and 30% nonunion in type II fractures. Several techniques had been described in the relevant literature. In our practice, fixation with Kirschner wires and tension-band wires has been successful in the treatment for displaced distal clavicle fracture.

Accidental Falls↗

Optimized protocols in terms of equalizing the true and accidental coincidences of each bed position in static multiple bed position carbon-11 PET studies and a target single bed position study.

Quantitative carbon-11 (11C) positron emission tomography (PET) is gaining more attention in oncological applications. In addition, it was discovered that accidental coincidences (randoms) can play an important role in studies such as partial volume effects correction without needing to use anatomical information. However, because of the short half-life of 11C, a homogeneous multiple bed position 11C image is hard to obtain. This study aimed to determine whether innovative pseudogating, optimized pseudogating and optimized double-up methods could match the true counts and randoms to each bed position and to a target single bed position study. A long cylindrical phantom filled with [11C]acetate was scanned by a dedicated PET scanner using six protocols: whole body, frame-duration-compensated whole body, double-up, optimized double-up, pseudogating, and optimized pseudogating. The differences between the protocols are in the initial activity, frame duration and frame number for each bed position. The parameters for pseudogating were determined according to the theory that true counts and randoms are proportional to the radioactivity and its square, respectively. The results show that the stated goals could only be achieved by pseudogating and optimized pseudogating. We conclude that pseudogating or optimized pseudogating must be applied for a critical quantitative study. However, optimized double-up and double-up methods are good alternatives for semi-quantitative and qualitative studies, respectively.

Algorithms↗

Debrisoquine 4-hydroxylase (CYP2D6) genetic polymorphisms and susceptibility to schizophrenia in Chinese patients from Taiwan.

Debrisoquine 4-hydroxylase (CYP2D6) is one of the cytochrome P450 enzyme families that metabolize many compounds. Polymorphic activities of debrisoquine 4-hydroxylase were suggested to be associated with some complex diseases, such as cancer and Parkinson's disease. Schizophrenia is also a complex disorder, and hence we are interested in understanding if the CYP2D6 gene is a susceptibility gene for schizophrenia in Chinese. We determined the genotype and allele frequencies of four molecular variants of CYP2D6 gene (i.e. 188C/T, 1934G/A, 2938C/T and 4268C/G) in 162 Chinese schizophrenic patients and 94 non-psychotic control subjects from Taiwan. No significant differences of allele or genotype frequencies of three polymorphisms (i.e. 188T/C, 2938C/T and 4268C/G) were detected between patients and control subjects. The 1934A allele, which accounts for the majority of poor metabolizers in Caucasians, was not detected in either patients or control subjects, indicating that the 1934A allele is very rare in Chinese. Our data suggest that the CYP2D6 gene may not be a susceptibility gene for schizophrenia in Chinese schizophrenic patients.

Alleles↗

Genetic polymorphisms of the promoter region of dopamine D2 receptor and dopamine transporter genes and alcoholism among four aboriginal groups and Han Chinese in Taiwan.

This study aims to examine the relationship between the functional polymorphism at the promoter region of the dopamine D2 receptor (DRD2) gene (i.e. -141C Ins/Del) and variable number of tandem repeat polymorphism at the 3' untranslated region of the dopamine transporter (DAT) gene (SLC6A3) with alcoholism in a case-control study. The cases (n = 203) were alcohol dependents with withdrawal symptoms, and the controls (n = 213) were sex- and ethnicity-matched individuals who were screened to exclude those with alcohol problems among four aboriginal groups (Atayal, Ami, Bunun, and Paiwan) and Han Chinese in Taiwan. To control for potential confounding factors, we excluded tobacco abusers from control subjects in part of the analysis and compared the distribution of the genetic polymorphisms in alcoholics with severe medical complications versus those with less severe medical complications. There were no differences in allele and genotype frequencies of these two distinct genetic markers between alcoholics and control subjects in these five different ethnic groups. There was no significant linkage disequilibrium between the -141C polymorphism and two other DRD2 polymorphisms (TaqI A and NcoI). The results remained unchanged when cases were limited to alcoholics with more severe medical complications or when tobacco abusers were excluded from control subjects. The results suggest that both the DRD2 promoter region and the DAT gene do not play a significant role in conferring vulnerability to alcoholism.

Adult↗

Trans-(DL-isoleucinato-N,O)[tris(2-aminoethyl)amine-kappa(4)N]cobalt(III)diperchlorate..

The racemic title compound, trans-[N,N-bis(2-aminoethyl)-1,2-ethanediamine-kappa(4)N](DL-isoleucinato-N,O)cobalt(III) diperchlorate, [Co(C(6)H(18)N(4))(C(6)H(12)NO(2))](ClO(4))(2), crystallizes in the enantiomorphous space group P2(1)2(1)2(1) with Z = 12 (Z' = 3). Each of the three cations in the asymmetric unit represents a different chirality of the isoleucine ligand; two of them are R (or D) and the third is the S (or L) enantiomer. The mixture crystallizes in a so-called unbalanced crystallization, in which the cations adopt a chiral array of composition RRS or SSR, depending on the crystal selected for data collection.

Journal Article↗

Overexpression of interferon gamma-inducible protein 10 in the liver of patients with type I autoimmune hepatitis identified by suppression subtractive hybridization.

OBJECTIVE: To clarify gene expression profiles in the liver may elucidate the pathogenesis of type I autoimmune hepatitis (AIH). Using suppression subtractive hybridization (SSH), we identified genes overexpressed in the liver of AIH. METHODS: A small liver biopsy sample from a patient with definite AIH was available to be analyzed in our system. By mixing cDNA synthesized from this sample as a 'tester' and cDNA from a normal liver as a 'driver,' we subtracted cDNA to enrich genes overexpressed in AIH. After polymerase chain reaction (PCR) amplification and subcloning, we identified subtracted genes by sequencing 50 randomly selected clones. RESULTS: Only one cDNA fragment, which is identical to interferon inducible protein 10 (IP-10), was overexpressed by > 10 times in the liver of AIH, as compared with control. We confirmed IP-10 overexpression in all eight patients with AIH by reverse transcription PCR. Immunohistochemical analysis demonstrated increased IP-10 expression in hepatocytes in the liver of AIH. Reverse transcription PCR analysis of 63 liver biopsy samples with various liver diseases revealed that IP-10 expression was significantly higher in AIH (p = 0.025) and chronic hepatitis C (p = 0.0043) than in other liver diseases. Interestingly, the amount of IP-10 mRNA expression was correlated with serum ALT values in AIH (p = 0.0006), but not in chronic hepatitis C (p = 0.43). CONCLUSION: These results indicate the IP-10 expression in the liver might be used as a preferential marker of AIH, and that IP-10 has some pathophysiological roles in the liver damage of AIH.

Alanine Transaminase↗

Role of human immunodeficiency virus (HIV) type 1 envelope in the anti-HIV activity of the betulinic acid derivative IC9564.

The betulinic acid derivative IC9564 is a potent anti-human immunodeficiency virus (anti-HIV) compound that can inhibit both HIV primary isolates and laboratory-adapted strains. However, this compound did not affect the replication of simian immunodeficiency virus and respiratory syncytial virus. Results from a syncytium formation assay indicated that IC9564 blocked HIV type 1 (HIV-1) envelope-mediated membrane fusion. Analysis of a chimeric virus derived from exchanging envelope regions between IC9564-sensitive and IC9564-resistant viruses indicated that regions within gp120 and the N-terminal 25 amino acids (fusion domain) of gp41 are key determinants for the drug sensitivity. By developing a drug-resistant mutant from the NL4-3 virus, two mutations were found within the gp120 region and one was found within the gp41 region. The mutations are G237R and R252K in gp120 and R533A in the fusion domain of gp41. The mutations were reintroduced into the NL4-3 envelope and analyzed for their role in IC9564 resistance. Both of the gp120 mutations contributed to the drug sensitivity. On the contrary, the gp41 mutation (R533A) did not appear to affect the IC9564 sensitivity. These results suggest that HIV-1 gp120 plays a key role in the anti-HIV-1 activity of IC9564.

Anti-HIV Agents↗

Induction and characterization of neutralizing antibodies against a human immunodeficiency virus type 1 primary isolate.

Chimpanzees infected with the primary isolate DH012 mount potent neutralizing antibodies. This DH012 neutralizing activity is highly strain specific. Immune sera from guinea pigs immunized with recombinant DH012 gp120 could also neutralize this primary isolate. The neutralizing activity in chimpanzee and guinea pig sera against wild-type DH012 appears to be independent of a linear epitope in the V3 region of gp120. Interestingly, the neutralization escape mutant derived from growing DH012 in the presence of the potent neutralizing chimpanzee serum is at least 50-fold more sensitive than wild-type DH012 to neutralization by guinea pig immune sera. The unusually potent neutralizing activity against the DH012 neutralization-resistant virus is due to the presence of anti-V3 antibodies in guinea pig sera. These results suggested that recombinant gp120 could induce neutralizing antibodies against primary isolate DH012. The V3 of wild-type DH012 is poorly immunogenic in infected chimpanzees and is not accessible to neutralizing V3 antibodies. It is likely that this cryptic V3 region became exposed when the virus escaped the neutralizing activity of the chimpanzee serum.

Animals↗

Sequences in the NS5A protein of hepatitis C virus and the serum alanine aminotransferase response to interferon therapy in Japanese patients.

BACKGROUND AND AIMS: Chronic hepatitis C is a slowly progressive disease and eventually causes hepatocellular carcinoma in many patients. Although interferon (IFN) therapy has been used for viral eradication, its success rate is only about 30%. In patients in whom it has failed (non-responders), there are several patterns of serum alanine aminotransferase (ALT) values, and detection of serum HCV-RNA during and after IFN therapy and improved long term prognosis were reported in patients whose serum ALT values were normalised by IFN therapy even if HCV viraemia persisted. The present study sought to clarify the virological characteristics contributing to these differences. METHODS: Complete or partial length dominant sequences of hepatitis C virus genotype 1b (HCV-1b) were determined by direct sequencing. Firstly, the complete sequences of HCV-1b genomes were determined in six non-responders; three showed normalisation of serum ALT values during IFN-alpha therapy and the other three did not. Subsequently, the amino acid residues that were different in the two groups were further analysed retrospectively in another 82 patients. RESULTS: Comparison of the sequences suggested an association between amino acids 2154-2172 of HCV-1b and serum ALT normalisation. A retrospective analysis of 82 patients revealed that the number of amino acid substitutions in this region was the only statistically significant variable associated with ALT normalisation (odds ratio 31.0; 95% confidence interval 5.0-286) in multivariate analyses. CONCLUSIONS: A HCV genomic region that correlates with the ALT response to IFN therapy appears to be present in virologically IFN ineffective patients.

Adult↗

Isolated talonavicular arthrodesis for talonavicular arthritis.

We have reviewed a single surgeon's experience with isolated talonavicular fusion in 16 patients with talonavicular arthritis. Fixation was either by staples or screws. Fifteen solid unions were achieved in the 16 patients who were followed (mean: 51 months). The average Ankle-Hindfoot Scale improved from 77.2 preoperatively to 92.9 postoperatively (p < 0.001). Subjectively, 15 patients were satisfied and one patient dissatisfied with the results. Further osteoarthritis in the adjacent joints was noted in five patients. We concluded that isolated talonavicular fusion is an effective method of treatment of talonavicular arthritis regarding pain relief and functional improvement. Though osteoarthritis was found in some adjacent joints postoperatively, the results were still satisfactory.

Adolescent↗

Targeting expression of the human vitamin D receptor to the keratinocytes of vitamin D receptor null mice prevents alopecia.

Vitamin D receptor (VDR) null mice develop hypocalcemia, hyperparathyroidism, rickets, osteomalacia and alopecia. Normalization of mineral ion homeostasis prevents all of these abnormalities except alopecia. Hair reconstitution assays, performed in athymic nude mice, demonstrate that the lack of VDR in keratinocytes leads to a defect in anagen initiation, similar to that observed in VDR null mice. Although these studies demonstrate that expression of the VDR in keratinocytes is necessary, they do not prove that it is sufficient for maintenance of the normal hair cycle. To address this hypothesis, we generated transgenic mice expressing the human VDR under the control of the keratin 14 (K14) promoter. Two highly expressing transgenic lines were mated with VDR null mice to obtain VDR null mice expressing the human VDR transgene (hVDR+/mVDR-). Expression of the transgene in the VDR null mice prevented alopecia. Furthermore, when subjected to anagen initiation, the hair follicle keratinocytes of the hVDR+/mVDR- mice demonstrated an enhanced proliferative response compared to those of control littermates. Restoration of VDR expression in the keratinocytes of VDR null mice, prevents the hair cycle defect that leads to the development of alopecia.

Alopecia↗