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Biomedical subjects

K H Lin

Publications and source records attributed to K H Lin.

At least 19 recordsLinked to original sources

Improved treatment results for childhood acute myeloid leukemia in Taiwan.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.

Adolescent↗

Post-poliomyelitis syndrome: case report and review of the literature.

INTRODUCTION: Postpoliomyelitis syndrome (PPS) refers to the new neuromuscular symptoms that occur in patients years after their acute poliomyelitis has stabilised. PPS cases seen now are probably related to the poliomyelitis epidemics of the 1940s and 1950s. CLINICAL PICTURE AND INVESTIGATION: A 57-year-old Chinese man with a history of poliomyelitis affecting both lower limbs presented with left upper limb weakness. Physical examination revealed atrophy of his left upper limb muscles. There were fasciculations in the biceps and brachioradialis muscles. Electromyography revealed ongoing denervation neurogenic units in the C5 to TI myotomes comparable with PPS. CONCLUSION: The aim of this paper is to review the present situation and to give a short summary of PPS, which can be difficult to diagnose because the symptoms of presentation are usually non-specific. We describe a case of PPS and review the current literature.

Electromyography↗

Field-induced structures in miscible ferrofluid suspensions with and without latex spheres.

We explore magnetic-field-induced ordering and microphase separation of aqueous ferrofluid and of aqueous mixtures of ferrofluid with nonmagnetic latex spheres. The ferrofluid is a surfactant stabilized aqueous suspension of magnetite (Fe3O4) particles with average diameter 20 nm (including the approximately 2.5-nm thick surfactant layer); the nonmagnetic latex spheres are charge stabilized polymethylmethacrylate (PMMA) particles with diameters of 42 nm, 108 nm, and 220 nm. In the presence of a uniform magnetic field, needlelike ferrofluid droplets formed that eventually grew to sample-traversing columns at fields of approximately 600 G; the two-dimensional structure of these columns was, however, glassy rather than hexagonal. In higher fields, approximately 1000 G, the columns stretched and coalesced into sheetlike striped liquids, but a true lamellar phase was not observed. The addition of nonmagnetic latex spheres to the ferrofluid suspension lowered substantially the critical field for the formation of columns, and induced lamellar (stripe) phases at relatively low applied fields. Image analysis was used to determine the spatial correlation functions, the average needle or column spacing, and the average lamellae spacing of these samples as a function of latex sphere size and concentration.

Journal Article↗

Aberrant caspase-activated DNase (CAD) transcripts in human hepatoma cells.

The gene of caspase-activated DNase (CAD), the key enzyme for nucleosome cleavage during apoptosis, is mapped at chromosome 1p36, a region usually associated with hemizygous deletions in human cancers, particularly in hepatoma (HCC). It is tempting to speculate that CAD plays a tumour-suppressive role in hepatocarcinogenesis. To address this, we examined the CAD transcripts in six human HCC cell lines, one liver tissue from a non-HCC subject, and peripheral blood leukocytes (PBL) from three healthy individuals. Alternatively spliced CAD transcripts with fusion of exon 1 to exon 7 were isolated in most of the examined samples including HCC cells and normal controls. However, relatively abundant alternatively spliced CAD transcripts with fusion of exon 2 to exon 6 or 7, in which the corresponding domain directing CAD interaction with ICAD was preserved, were found only in poorly differentiated Mahlavu and SK-Hep1 cells. Interestingly, an abnormal CAD transcript with its exon 3 replaced by a truncated transposable Alu repeat was isolated in Hep3B cells, indicative of the implication of an Alu-mediated genomic mutation. Moreover, mis-sense mutations in the CAD genes were identified in all six HCC cell lines. Upon UV-induced apoptosis, DNA fragmentation efficiency was found to be intact, partially reduced and remarkably reduced in Huh7 and J328, Hep3B and HepG2, and Mahlavu cells, respectively. That mutations and aberrantly spliced transcripts for the CAD gene are frequently present in human HCC cells, especially in poorly differentiated HCC cells, suggests a significant role of CAD in human hepatocarcinogenesis.

Alternative Splicing↗

Decommissioning of a 60Co unit and estimation of personal doses.

Chang-hua Christian Hospital needs to uninstall the 60Co unit. The mode of this 60Co teletherapy unit is SHIMADZU RTGS-10. The original lead head was taken as the source container of this 60Co unit. The source head was dismantled and put into the prepared wooden box, after the source was sealed. This study describes the planning and dismantling of the retirement and transport of the 60Co unit, and personal doses measured during the procedure. This work estimates the doses of radiation received by exposed workers during the dismantling of the machine. The workers received doses of approximately 53 microSv. This study shows that the original lead head can be used as the source container of this 60Co unit. The 60Co machine was smoothly dismantled and transported by conscientious and careful workers, using planned and controlled radiation protection, following the ALARA (as low as reasonably achievable) rule.

Body Burden↗

Micronized ethylcellulose used for designing a directly compressed time-controlled disintegration tablet.

Ethylcellulose (EC) of varying particle sizes has been used as an outer coating layer to design a novel dry-coated tablet with time-controlled drug release. This dry-coated tablet, containing a core tablet of sodium diclofenac and an outer coating layer of EC, was prepared by direct compression. The drug release from dry-coated tablet exhibited an initial lag period that was dependent on the particle size of the EC powder, followed by a stage of rapid drug release. The smaller the EC particle size used the longer the lag time obtained, suggesting the particle size of EC powder could modulate the timing of drug release from such a dry-coated tablet. The period of the lag time for sodium diclofenac released from dry-coated tablets was correlated with the penetration distance of the solvent into dry-coated tablet by an in vitro dye penetration study. The densest packing of EC powders appeared on the upper and lower surfaces of dry-coated tablet after compression, resulting in a tight structure yielding a slower penetration of the solvent. Whereas loose packing of EC powders occurred in the middle of the lateral surface of dry-coated tablet, this loosely packed surface readily allowed solvent penetration and that finally caused the splitting of tablet shell into two halves in the dissolution medium. The results suggest that these dry-coated tablets prepared with different particle sizes of EC powder as an outer coating layer might offer a desirable release profile for drug delivery at the predetermined times and/or sites.

Cellulose↗

Genetic analysis of recent Taiwanese isolates of a variant of coxsackievirus A24.

Epidemics of acute hemorrhagic conjunctivitis (AHC) caused by a variant of coxsackievirus A24 (CA24v) reappeared in Taiwan in 1990 and 1994, following the first two epidemics of 1985--86 and 1988--89. To analyze the genetic diversity of recent CA24v in Taiwan, 7 Taiwanese strains isolated during the 1990--94 period were studied together with one Japanese and two Thai strains isolated in 1993. A fragment of 674 nucleotides between the carboxy terminal 3A and the amino terminal 3D polymerase, including the entire 3C protease (3C(pro)), was amplified by a reverse transcription-polymerase chain reaction (RT-PCR) and the nucleotide sequences were determined. In the 549 nucleotides (183 amino acids) of the entire 3C(pro), we found nucleotide differences at 80 positions between 10 strains and the prototype strain, EH24/70, one of the earliest strains of CA24v. Most of the nucleotide changes were synonymous substitutions and only nine amino acid changes were found. The nucleotide sequence homologies among 71 strains worldwide were 88-100%. These 71 nucleotide sequences were then analyzed by Neighbor-joining method and phylogenetically separated into three distinct genotypes. Genotype I consisted of early strains isolated in 1970--71 from Singapore and Hong Kong. Genotype II included isolates from Singapore and Thailand obtained in 1975. Genotype III comprised strains from the eastern hemisphere isolated in 1985--94 from Japan, Taiwan, China, Hong Kong, Thailand, Singapore, Pakistan and Ghana. They were further divided chronologically into six clusters. The recent isolates from Taiwan obtained in 1985/1986, 1988/1989 and 1990--94 were classified into genotype III Clusters 1, 5, and 6 respectively. The evolutionary rate was re-estimated to be 3 x 10(- 3) 30 years after the emergence of the virus.

Amino Acid Sequence↗

Compression forces and amount of outer coating layer affecting the time-controlled disintegration of the compression-coated tablets prepared by direct compression with micronized ethylcellulose.

The influence of compression force to inner core tablet or to outer coating layer of the compression-coated tablet on the function of time-controlled disintegration was investigated. The inner core tablet was directly compacted by sodium diclofenac (model drug) and ethylcellulose (EC) with 4.6-microm particle size was used as an outer coating layer. The immersion time of the compression-coated tablet previously soaked in pH 1.2 solution to simulate the residence time of the tablet in the GI tract affecting the dissolution behavior of the compression-coated tablet was also investigated. The effect of the amount of the outer coating layer used on the drug release was examined. The results indicate that sodium diclofenac released from these compression-coated tablets exhibited a longer lag of a period about 16.3 h in both distilled water and pH 6.8 buffer solution, followed by a different drug release behavior. The lag time was independent of the pH of dissolution medium, and the immersion time in pH 1.2 solution. After that lag time, the outer shell of the compression-coated tablets broke into two halves to make a rapid drug release. However, the drug release behavior of the soaked tablet in pH 6.8 buffer solution was dependent on the immersion time. The compression force < 200 kg/cm(2) to the inner core tablet influenced the release behavior of drug less, but > 200 kg/cm(2) might delay the lag time. The lag time of the compression-coated tablets was linearly correlated with the compression force to the outer coating layer (r = 0.9896). We also found that the more the amount of outer coating layer added, the longer the lag time obtained. The study demonstrates that the time-controlled disintegration of the compression-coated tablet was effectively controlled by the compression force applied and the amount of outer coating layer added.

Cellulose↗

Philadelphia chromosome-positive acute lymphoblastic leukemia in Taiwan.

From January 1986 to December 1998, 26 (23%) of 114 acute lymphoblastic leukemia (ALL) patients older than 15 years were found to have Philadelphia (Ph) chromosome. They accounted for 28% (26 of 94) of the patients with B-lineage ALL. Compared with the other 88 ALL patients, the leukemic cells from all but one Ph-positive ALL patients were early pre-B cells with a higher rate of CD34 expression (92% vs 50%, P<0.05). At presentation, the Ph-positive adult ALL patients had higher circulating blasts (mean 21.4 vs 3.66x10(4)/microl, P<0.05) and lower initial platelet counts (mean 4.47 vs 7.34x10(4)/microl, P<0.01) and showed a trend toward higher frequency of initial central nerve system (CNS) involvement (25% vs 11%, P=0.098) than the others. Among patients with adequate chemotherapy, 16 (64%) of the 25 Ph-positive ALL patients achieved complete remission (CR), an incidence marginally lower than that of Ph-negative ALL (62 of 76, 82%, P=0.06) and significantly lower than that of Ph-negative B-lineage ALL (50 of 58, 86%, P=0.0037). However, all patients relapsed except for those who received allogeneic hemopoietic stem cell transplantation (allo-HSCT). The probabilities of 5-year continuous CR and 5-year survival for Ph-positive adult ALL patients were significantly inferior to those for Ph-negative adult ALL patients (0% vs 12%, P=0.0001, and 7% vs 19%, P=0.047, respectively), and those for Ph-negative B-lineage ALL (0% vs 14%, P<0.0001, and 7% vs 23%, P=0.002, respectively). Prognostic factors were analyzed among the Ph-positive ALL patients including the 26 adults mentioned above and an additional 11 children. No clinical or biological characteristics such as age, sex, initial circulating blast count, extramedullary involvement, or CD34 expression had an impact on the disease outcome. Allo-HSCT in first CR may improve the probability of 5-year continuous CR (100% vs. 0% for those without allo-HSCT, P=0.0091) although only three patients received it in this study. In conclusion, Ph-positive ALL patients tended to have a poor prognosis, regardless of whether other possible risk factors were present or not. Aggressive treatment, such as high-dose chemotherapy with allo-HSCT, should be considered for these patients to improve survival.

Adolescent↗

Molecular epidemiology of enterovirus 71 in Taiwan.

Taiwan suffered a severe and widespread outbreak of enterovirus infection in 1998. More than 400 children were hospitalized, with seventy-eight fatalities due to central nerve system (CNS) involvement and cardiopulmonary collapse. Enterovirus 71 (EV71) was incriminated as the causative agent for the fatal cases. To understand the viral molecular epidemiology in this outbreak, fragments of 207-bp length of the VP4 region in 23 Taiwanese EV 71 isolates were sequenced. Pair-wise comparison revealed a 17.5-24.4% difference between the isolates and the prototype BrCr. However, all the changes in the VP4 region of the isolated strains were synonymous substitutions. Phylogenetic analysis was performed on these 23 isolates and 21 others deposited in GenBank. In this study, forty-four EV71 isolates from the world were separated into three distinct genotypes: A, B and C. The EV71 prototype strain, BrCr/70, is the only strain of genotype A. Group B included strains from the United States, Japan and Taiwan. Most strains in genotype B were isolated prior to 1990. Group C consisted of strains from Japan and Taiwan. Most strains of genotype C were isolated after 1990, they were further divided into 3 clusters: i.e. C-1, C-2 and C-3. In Taiwan, two genotypes, B and C-3, were co-circulating during the outbreak in 1998, although a minor group of genotype B may have appeared in Taiwan before 1986. The majority of the isolates clustered in genotype C-3. Genotype C showed a higher evolutionary rate than genotype B (3.9 x 10(-3) vs. 1.4 x 10(-3)) in the VP4 region. There seems to be a worldwide trend with strains of genotype B appearing earlier than strains of genotype C which took over later in the dominance.

Base Sequence↗

The effects of aging on AV nodal recovery properties.

The purpose of this study was to assess the changes of AV nodal recovery properties with aging. Although in children and young adults it was found that there were age dependent changes in their AV nodal recovery properties, in the older population this information was not available. In 92 subjects (aged 16-92 years) without AV nodal disease or dual AV nodal pathway physiology, their AV nodal recovery curves were studied by delivering premature atrial extrastimuli coupled to basic atrial beats during cardiac electrophysiological study. Data were analyzed using linear regression and curve-fitting techniques. Patients were grouped by age, group I < 40 years (n = 33), group II 40-59 years (n = 26), and group III > 60 years (n = 33). The results showed that the AV nodal recovery curve did not change significantly in the aging process except that the AV nodal effective refractory period had a positive correlation with increasing age. The latter was significantly increased in group III when compared to group I or group II. For this parameter, when patients whose AV nodal refractory period was limited by the atrial refractory period were excluded, there was still a statistically significant increase in group III compared to group II (P < 0.05): group I (n = 27): 202+/-42 ms; group II (n = 17): 197+/-26 ms; and group III (n = 17): 224+/-46 ms. The results suggest that the AV nodal recovery curve remains unchanged once it reaches adulthood, with the exception that the nodal effective refractory period becomes slightly longer after age 60.

Adolescent↗

Hemorrhagic viral keratoconjunctivitis in Taiwan caused by adenovirus types 19 and 37: applicability of polymerase chain reaction-restriction fragment length polymorphism in detecting adenovirus genotypes.

PURPOSE: Acute keratoconjunctivitis with prominent subconjunctival hemorrhage (SCH) is usually perceived by a clinician as acute hemorrhagic conjunctivitis (AHC) associated with enteroviruses; however, SCH can also be an adenoviruses infection. A rapid and sensitive laboratory diagnosis is helpful for differential diagnosis. Therefore, the sensitivity and applicability of polymerase chain reaction (PCR) and reverse transcription (RT)-PCR diagnoses were evaluated for keratoconjunctivitis associated with viral infection. METHODS: Conjunctival swabs from patients with acute conjunctivitis were tested using a PCR-restriction fragment length polymorphism (PCR-RFLP) for adenovirus detection and RT-PCR for enterovirus detection. The results were compared with those using the culture isolation and neutralization test; also, the clinical findings of the patients were analyzed with special attention to SCH patterns. RESULTS: Neither coxsackievirus A type 24 variant (CA24v) nor enterovirus type 70 (EV70) was detected in 113 patients with acute conjunctivitis. The positive results of adenovirus (Ad) were 39.9% by the PCR method and 37.1% by culture isolation. For the patients with adenoviral conjunctivitis, 68.1% was owing to Ad37 and 19.2% was owing to Ad19. SCH was present in 51.5% of the positive cases, and 44.7% of the Ad-positive patients had secondary illnesses. CONCLUSIONS: SCH can be a predominant presentation of Ad19 and Ad37 keratoconjunctivitis and may herald a new stage in the evolution of adenoviruses. PCR and PCR-RFLP are rapid and reliable methods for Ad detection and typing; however, if the amplified genes and restriction enzymes are not properly selected, they may not be able to detect new genotypes of adenoviruses or the evolution of these viruses.

Adenovirus Infections, Human↗

Impaired interaction of mutant thyroid hormone receptors associated with human hepatocellular carcinoma with transcriptional coregulators.

Thyroid hormone (T(3)) exerts its many biological activities through interaction with specific nuclear receptors (TRs) that function as ligand-dependent transcription factors at genes that contain a thyroid hormone response element (TRE). Mutant TRs have been detected in human hepatocellular carcinoma cell lines and tissue, but their contribution to carcinogenesis has remained unclear. The interaction of four such mutant TRs (J7-TRalpha1, J7-TRbeta1, H-TRalpha1, and L-TRalpha1) with transcriptional coregulators has now been investigated. With the exception of J7-TRalpha1, which in the absence of T(3) exhibited transcriptional silencing activity with a TRE-reporter gene construct in transfected cells, the mutant TRs had little effect (compared with that of wild-type receptors) on transcriptional activity of the reporter gene in the absence or presence of T(3), of the transcriptional corepressors SMRT, NCoR or of the transcriptional coactivator SRC. Electrophoretic mobility-shift assays revealed that, in the presence of T(3), the J7-TRss1 mutant did not interact with SRC, whereas J7-TRalpha1 and H-TRalpha1 exhibited reduced abilities to associate with this coactivator and L-TRalpha1 showed an ability to interact with SRC similar to that of wild-type TRalpha1. The dominant negative activity of the mutant TRs in transfected cells appeared inversely related to the ability of the receptors to interact with SRC. Whereas J7-TRss1, H-TRalpha1, and L-TRalpha1 did not interact with SMRT, and NCoR. J7-TRalpha1 bind to corepressors but failed to dissociate from them in the presence of T(3). These aberrant interactions between the mutant TRs and transcriptional coregulators may contribute to the highly variable clinical characteristics of human hepatocellular carcinoma.

Animals↗

Screw-in atrial lead in a sick sinus syndrome patient with anomalous inferior vena cava.

Anomalous inferior vena cava without intracardiac anomaly is an unusual condition. Herein, we report a 48-year-old female with left-sided inferior vena cava and azygous continuation. accompanied by sick sinus syndrome. This anomaly resulted in difficulty in implanting a traditional hook-on atrial lead. Atrial lead dislodgment occurred repeatedly soon after implanting the pacemaker because of an anomalous zygous vein draining into the superior vena cava, making a giant connection with the right atrium, thus eliminating the space of the atrial appendage for lead lodgment. Finally, we attempted to utilize a screw-in atrial lead in this patient and she is currently doing well. We therefore suggest that a screw-in atrial lead should be taken into account for such patients in order to obtain a stable fixation.

Azygos Vein↗

Abnormal glucose tolerance in transfusion-dependent beta-thalassemic patients.

OBJECTIVE: To study the prevalence of and risk factors for abnormal glucose tolerance in transfusion-dependent beta-thalassemic patients. RESEARCH DESIGN AND METHODS: A total of 89 transfusion-dependent beta-thalassemic patients were interviewed. Diabetes was previously diagnosed in 14 of them. In the remaining 75 patients, 68 participated in an oral glucose tolerance test. Potential risk factors were identified using the independent t test, chi2 test, and Fisher's exact test. Logistic regression analysis was used to select the independent risk factors that best predicted abnormal glucose tolerance A two-tailed P value of <0.05 was considered to be statistically significant. RESULTS: The prevalence of impaired glucose tolerance was 8.5% (7 of 82) and that of diabetes was 19.5% (16 of 82). Presentation with diabetic ketoacidosis was 31.1% (5 of 16). The risk factors for abnormal glucose tolerance found in transfusion-dependent beta-thalassemic patients were serum ferritin concentration and hepatitis C infection. CONCLUSIONS: The interaction of iron overload and hepatitis C infection worsened the prognosis of thalassemic patients. Aggressive iron-chelation therapy as well as prevention and treatment of hepatitis C infection should be mandatory in managing glucose homeostasis in transfusion-dependent beta-thalassemic patients in Taiwan.

Adolescent↗

Emerging new frontiers in cardiac pacing: cardiac pacing in heart failure.

Indications for pacing have leapt beyond sinus node dysfunction and atrioventricular (AV) block. Pacing for the purpose of improving hemodynamics has become the prime subject of exploration. Several studies have reported hemodynamic and clinical improvement with bi-ventricular pacing and AV sequential pacing. Data is still pouring in from the various ongoing trials regarding the beneficial effects of these methods of pacing. This is especially true in a subset of patients with intractable heart failure. There are several indicators to identify these patients. Those who have intra-ventricular conduction defects and those who demonstrate hemodynamic improvement after temporary pacing are certainly the candidates who will benefit most from this new form of pacing. Prolonged PR interval or left bundle branch block with intractable heart failure also falls into this category. The rationale of pacing in heart failure is to correct the cardiac dysynchrony that occurs frequently in these patients. Cardiac dysynchrony can occur due to ineffective synchronization between atria and ventricles (AV dysynchrony) or due to lack of synchronization within the two ventricles (ventricular dysynchrony). This is overcome by AV sequential pacing or by multi chamber pacing using the coronary sinus as portal of entry of the electrode into the cardiac vein to pace the left ventricle. Pacing leads and generators have been designed to suit the new found methods of pacing. Clinical trials are in full swing to establish the efficacy of these methods.

Cardiac Pacing, Artificial↗