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Anti-hypertensive medications may affect plasma renin activity and/or plasma aldosterone concentration, misleading the interpretation of the aldosterone-to-renin ratio when screening for primary aldosteronism. The Task Force of Taiwan PA recommends that, when necessary, using α-adrenergic receptor blocking agents, centrally acting α-adrenergic agonists, and/or non-dihydropyridine calcium channel blockers should be considered to control blood pressure before screening for PA. We recommend temporarily holding β-adrenergic receptor blocking agents, mineralocorticoid receptor antagonists, dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and all diuretics before screening for PA. Further large-scale randomized controlled studies are required to confirm the recommendations. [ABSTRACT FROM AUTHOR]

Mass spectrometry (MS) assays offer exceptional capabilities in high multiplexity, specificity, and throughput. As proteomics technologies continue advancements to identify new disease biomarkers, transition of these innovations from research settings to clinical applications becomes imperative. To meet the rigorous regulatory standards of clinical laboratories, development of a clinical protein MS assay necessitates adherence to stringent criteria. To illustrate the process, this project focused on using thyroglobulin (Tg) as a biomarker and an immuno-multiple reaction monitoring (iMRM) MS-based assay as a model for establishing a Clinical Laboratory Improvement Amendments (CLIA) compliant laboratory within the Centers of Genomic and Precision Medicine, National Taiwan University. The chosen example also illustrates the clinical utility of MS assays to complement conventional immunoassay-based methods, particularly in cases where the presence of autoantibodies in 10–30% of patients hinders accuracy. The laboratory design entails a comprehensive coordination in spatial layout, workflow organization, equipment selection, ventilation systems, plumbing, electrical infrastructure, documentation procedures, and communication protocols. Practical aspects of the transformation process, including preparing laboratory facilities, testing environments, instrument validation, assay development and validation, quality management, sample testing, and personnel competency, are discussed. Finally, concordant results in proficiency testing demonstrate the harmonization with the University of Washington Medical Center and the quality assurance of the CLIA-equivalent Tg-iMRM MS assay established in Taiwan. The realization of this model protein MS assay in Taiwan highlights the feasibility of international joint development and provides a detailed reference map to expedite the implementation of more MS-based protein assays in clinical laboratories for patient care. [ABSTRACT FROM AUTHOR]

Purpose: This study explores whether institutional investors can distinguish an undervalued share repurchase from a falsely signaled share repurchase. This study also aims to determine what information institutions use when investing in repurchase stocks. Design/methodology/approach: This study uses unique Taiwanese data and concentrates on foreign institutions because they are the most sophisticated investors in Taiwan. Findings: The results show that foreign institutional trading in open market repurchase (OMR) stocks will earn both positive concurrent and post-OMR excess returns. In addition, there is a significant positive relationship between pre-OMR insider trading and foreign institutional trading during the OMR period; that is, foreign institutions follow insiders to trade their OMR stocks. Practical implications: This study finds that foreign institutions use publicly available data on insider trading to choose OMR stocks and create excess returns. This encourages individual investors without private information, who can also earn a positive return if they diligently study available public information. Originality/value: This study contributes to the international investment literature by determining the price impacts associated with foreigner trading in the firm-level returns of the host country. In addition, this study finds that foreign institutions choose OMRs based on insider trading information, which fills the gap in existing studies on share repurchasing. Moreover, this study enriches the insider literature by showing how foreign institutions can benefit by using insider trading information. [ABSTRACT FROM AUTHOR]

Background/purpose: Surgery followed by radioiodine is a mainstay of treatment for thyroid cancers of follicular origins. However, about 5% of the thyroid cancers are non-operable and/or radioiodine-refractory diseases, which are either locally advanced or metastatic and result in a survival of less than 5 years. How to treat this population of thyroid cancer patients becomes a critical issue requiring further understanding of the tumor's genetic information.Methods: We used formalin-fixed paraffin-embedded specimens of 22 fatal thyroid cancers and their corresponding non-tumor parts, if available, to yield genomic DNA, and applied the Ion Torrent™ Personal Genome Machine (IT-PGM) System (Life Technologies), a next generation sequencing technology, to interrogate 740 mutational hotspots in 46 oncogenes. We further validated the results by conventional direct sequencing.Results: We confirmed 21 mutations of 11 oncogenes in the 22 fatal thyroid cancer samples. Among them, the MET p.N375S and MLH1 p.V384D mutations, each was detected in two cases, and has rarely been found to be involved in thyroid cancer pathogenesis before. We also identified homozygous PDGFRA p.V824V mutation in eight out of the 22 cases, while the non-tumor counterparts carried heterozygous PDGFRA p.V824V mutation. We noted that the Ion Torrent technique unfortunately showed high false positive rates for detecting EGFR mutations in thyroid cancers.Conclusion: The extensive genetic studies provide new insights to future targeted therapy in these patients. IT-PGM proved to be valuable for comprehensively searching genetic mutations in potentially fatal thyroid cancers. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade-based immunotherapy is a new modality of cancer treatment with a unique mechanism that has gained increased numbers of indication and is now used in several cancer types. However, immune-related adverse events (irAEs) emerge as a new entity of diseases involving one or multiple organ systems. irAEs could result in interruption of immunotherapy, morbidities or even death. Among various manifestations of irAEs, immune-mediated hypophysitis is rare but important, requiring prompt diagnosis and treatment to avoid life-threatening conditions. We report seven cases of immune-mediated hypophysitis in Taiwan. They suffered from various types of advanced cancer and received different regimens of immune checkpoint inhibitors. The time of onset after initiation of immunotherapy ranged from 5 to 36 weeks. All seven subjects were diagnosed of central adrenal insufficiency, while four of them had primary hypothyroidism. There was no typical finding of infiltrative hypophysitis on the pituitary MRI. There was no documented hormone recovery after diagnosis of hypophysitis, and the tumor responses to immunotherapy were variable in these seven patients. In conclusion, immune-mediated hypophysitis is often irreversible. Fortunately, it can be managed adequately with hormone replacements. Further investigations are warranted to unveil underlying mechanisms and ethnic differences to guide the solutions. [ABSTRACT FROM AUTHOR]

This article uses Buy-Sell Imbalance (BSI) as an indicator of investment behaviour to analyse the correlation between investor trading behaviours and returns of Initial Public Offerings (IPOs). After controlling for variables, such as market excess return, the size factor, and the book-to-market factor and momentum factor, this article finds that if IPOs are more popular to individual investors when issuing, the short-term returns are higher. In contrast, there is little sign that institutional investors exhibit such effect. In Taiwan's stock market where individual investors are the dominant players, the investment behaviours of individual investors exhibit certain influences on IPO share prices. This article also divides the IPO samples into two groups, one group favoured by investors and the other not at the time of issue. The result shows that IPOs favoured by individual investors have significantly lower long-term returns after 1 year of their listings, while IPOs favoured by institutional investors have different results. The two groups show no significant differences in average operational performances; therefore, this article suggests that the price correction of overly optimistic individual investors is the reason for the poorer long-term returns of IPOs favoured by individual investors. [ABSTRACT FROM PUBLISHER]

Background/purpose: Laboratory analytical turnaround time represents laboratory effectiveness. Our study aimed to evaluate laboratory analytical turnaround time to optimize workflow and shorten analytical turnaround time.Methods: We used the laboratory information system in a 2000-bed teaching hospital to compute and analyze the 90th percentile turnaround time of the Stat Laboratory from 2001 to 2003.Results: The overall 90th percentile turnaround time in the Stat Laboratory was 40-49 minutes and positively correlated with test volume. The daily test volume in the Stat Laboratory has grown significantly in the latter 2 half-years of the study as compared with the previous 2 half-years (p < 0.05 and p < 0.001, respectively). The daily longest turnaround time occurred in the early morning, and troponin-I testing contributed to the majority of incidences of prolongation of analytical turnaround time. We prioritized the performance of troponin-I testing, which resulted in a reduction of the analytical turnaround time by about 18 minutes (from 66 to 48 minutes) and no increment of overall turnaround time (42 to 44 minutes) despite continuously increasing test volume.Conclusion: These findings demonstrated that a dedicated means of process control was able to significantly improve laboratory efficiency. [ABSTRACT FROM AUTHOR]

Isovaleric acidemia (IVA), a rare autosomal recessive disorder in leucine metabolism caused by defected IVD gene, is characterized by episodes of acute metabolic crisis and psychomotor development retardation. This study aimed to determine the clinical, biochemical, and mutation spectrum of patients with IVA from mainland China. Eight patients (three boys and five girls) from eight unrelated families were collected, IVD gene mutations and phenotypes were examined. The patients were admitted because of vomiting, feeding difficulty, psychomotor retardation and "dirty sock" odor. Elevated blood isovaleryl (C5)-carnitine and urine isovalerylglycine were detected from all our patients. Fourteen mutations of the IVD gene were detected, eight of them are novel, c.145C>T (p.Q49Ter), c.359G>A (p.R120Q), c.424C>T (p.R142C), c.458T>C (p.L153P), c.466-1G>T, c.676_677insA (p.T226Nfs*13), c.1039G>A (p.A347T) and c.1076A>G (p.D359G). With this study, a total of 34 alleles were studied in the Chinese population. c.1208A>G (p.Y403C), the common mutation in Taiwan, accounts for 9/34 alleles (7 in previous reports and 2 in this study). We described eight novel mutations detected from eight unrelated Chinese patients and provided evidence to support that the p.Y403C is the hotspot mutation in this population. • Fifteen mutations of the IVD gene were identified from eight Chinese IVA patients. • Eight novel mutations were found. • The mutation p.Y403C is the hotspot mutation in the Han Chinese population. [ABSTRACT FROM AUTHOR]

Background: Human papilloma virus (HPV) has been implicated in the carcinogenesis and prognosis of certain head and neck cancers. Whether it also has a role in the pathogenesis of nasopharyngeal carcinoma (NPC) in Taiwan is unclear., Methods: Detection and genotyping of HPVs were performed in 43 primary NPCs (one WHO-I and 42 WHO-II/III) and 40 nasopharyngeal controls using PCR-based HPV genotyping arrays. Localisation of high-risk HPV and Epstein-Barr virus genomes was performed in another 46 primary NPCs (five WHO-I and 41 WHO-II/III) and seven paired metastatic WHO-II/III NPCs using in situ hybridisation., Results: In the HPV genotyping cohort, oncogenic HPVs were detected equally in WHO-II/III NPCs (31%, 13/42) and nasopharyngeal controls (35%, 14/40). Tumour high-risk HPV status did not correlate with the prognosis of patients with NPC. In the high-risk HPV in situ hybridisation cohort, 14 (88%) of the 16 oncogenic HPV-positive WHO-II/III NPCs showed a unique cytoplasmic/perinuclear staining pattern, which is distinct from the typical dot/punctate nuclear staining pattern indicating HPV genome integration. In addition, oncogenic HPVs were not always retained in NPC cells during the process of metastasis., Conclusions: This study does not support an association between oncogenic HPV and the carcinogenesis or prognosis of WHO-II/III NPCs in Taiwan.

Nasopharyngeal carcinoma (NPC) is an epithelial tumor uniquely prevalent in southern Chinese. HLA-A2 is associated with NPC. In a previous study, we showed that the genes associated with susceptibility to NPC are primarily located within the HLA-A locus in Taiwanese NPC patients. However, the pathogenic genes causing NPC susceptibility remain unknown. Here, 8 polymorphic microsatellite markers distributed over a 1 megabase region surrounding the HLA-A locus were subjected to genetic analysis for the NPC-susceptibility locus. Statistical studies of associated alleles detected on each microsatellite locus showed that the NPC- susceptibility genes are most likely located between the D6S510 and D6S211 markers within a 132 kb segment containing the HLA-A locus. These results undoubtedly would facilitate the further positional cloning of the NPC-susceptibility locus, which has been elusive for the past 30 years., ((c) 2005 Wiley-Liss, Inc.)

Approximately 30% of apparently Rh- Taiwanese people actually were RhD(el), a rare variant of the Rh system that might carry a grossly intact RHD gene. Several studies have indicated that the RhD(el) trait might be generated by multiple molecular mechanisms. In this study, a total of 294 Taiwanese serologically RhD- blood donors were tested for Rh phenotypes and RHD genotypes. Among them, total RHD deletion, partial RHD gene, and RhD(el) were found in 185 (62.9%), 15 (5.1%), and 94 (32.0%), respectively. The 1227A allele and exon 9 of the RHD gene were found in all 94 RhD(el) donors. The Ccee was the most prevalent phenotype in the RhD(el) group (78/94 [83%]), and the ccee phenotype was highly prevalent in the true D- group (87.6%). RHD 1227A can be used as an important and useful genetic marker for RhD(el). It can be detected easily by a simple, rapid, specific sequence primer-polymerase chain reaction method.

Oral cancer is the fourth leading cause of cancer deaths among men in Taiwan and is closely associated with areca quid chewing habits. Recent studies showed that mitochondrial DNA (mtDNA) mutations occur in various tumors, including oral cancers, and that the accumulation of mtDNA deletions could be an important contributor to carcinogenesis. Using laser microdissection, we have analyzed mtDNA deletions by pairwise comparisons in oral cancer, precancerous cells, and their adjacent submucosal stoma tissues in 12 patients with areca quid chewing history. Real-time quantitative polymerase chain reaction (RTQPCR) was performed to detect and quantify mtDNA with the 4,977-bp deletion in the histologically defined specified cell groups. Quantitative analysis of 60 samples by RTQPCR revealed that the average proportions of 4,977-bp deleted mtDNA over total mtDNA were 0.137%, 0.367%, and 0.001% in cancer, precancer cells, and lymphocytes of lymph node biopsies, respectively. Pairwise analysis of the proportion of mtDNA deletion in cancer, precancer, and their stroma tissues revealed a consistent trend among these patients. All of the patients (12/12) presented a higher proportion of mtDNA with 4,977-bp deletion in the lesions than in the lymphocytes, with average increases of 198-fold in cancer and 546-fold in precancer cells. A decrease in the proportion of deleted mtDNA was observed in 8 of 12 patients when the disease progressed from precancer to cancer lesions. Interestingly, 7 of 12 cancer tissues and 8 of 12 precancer lesions exhibited an average of 6.3-fold and 17.4-fold increases in the proportion of 4,977-bp deleted mtDNA in the stromal cells than in the lesion cells, respectively. The observation that the proportion of 4,977-bp deleted mtDNA in all oral lesions was higher than normal and consistently decreased during cancer progression from precancer to primary cancer suggests that accumulation and subsequent cytoplasmic segregation of the mutant mtDNA during cell division may play an important role in oral carcinogenesis. This study also demonstrates that laser microdissection combined with RTQPCR is an efficient and sensitive tool to gain insight into the role that mtDNA mutation may play in carcinogenesis.

NPC is an epithelial tumor that is highly prevalent among the southern Chinese. Numerous studies have indicated that specific HLA haplotypes and genes within the HLA complex are associated with NPC. As a first effort to localize the gene responsible for susceptibility, the HLA-A, -B, and -A2 subtypes were examined for their association to NPC. Consistent with previous reports, frequencies of HLA-A2 [OR = 2.50, pc = 0.020 (study population); OR = 3.73, pc = 0.0030 (> or =40 years old)] were significantly higher in patients with NPC than in healthy controls. Two-locus analysis indicated that A2(+)B46(+) individuals are at greater risk for NPC than A2(-)B46(-) individuals in both the population studied and the > or =40-year-old group. This, however, may be due to the close linkage of these 2 genes. Moreover, A2(+)B38(+) individuals were at higher risk than A2(-)B38(-) individuals in both the population studied and the > or =40-year-old group; A2 and B38 are not genetically linked. These findings suggest that B38 or B46 alone cannot confer a high risk of NPC but that, in conjunction with A2, B38 or B46 positivity greatly increases risk. None of 5 A2 subtypes identified from studied populations was significantly associated with NPC. Microsatellite marker D6S211, located 97 kb telomeric to HLA-A, was analyzed for its association with NPC. Allele 4 of D6S211 was significantly associated with NPC (OR = 3.97, pc = 0.0042). These results strongly support the hypothesis that genes associated with susceptibility to NPC in the HLA region are within the HLA-A locus., (Copyright 2002 Wiley-Liss, Inc.)

Betel quid (BQ) chewing has been a well-documented cause of oral epithelial lesions (OEL). Evolution from early hyperplastic lesions to the late or carcinomatous stage has been recognized. The pathobiological and molecular mechanism, however, remains to be elucidated. In this study, a total of 232 samples obtained from 153 cases of BQ-related OEL were retrospectively evaluated for the expression of p53 and bcl-2 in comparison with 26 cases of BQ-unrelated lesions (n = 29). The possible role of human papillomavirus (HPV) was also investigated. These BQ-related OELs included verrucous hyperplasia (VIH, n = 57, 24.6%), epithelial dysplasia (n = 23, 9.9%), verrucous carcinoma (VC, n = 5, 2.1%) and squamous cell carcinoma (SCC, n = 106, 45.7%). Fifty-four cases (35.3%) had multiple lesions. In comparison with the BQ-unrelated OELs, the characteristics of BQ-related OELs were a younger age, male predilection and multicentricity. In contrast to the tongue in BQ-unrelated OELs, the most common site for all types of BQ-related lesions was the buccal mucosa. Immunohistochemical studies of BQ-related lesions showed p53 staining in 30% of dysplasia and 38% of SCC, but a consistent absence in VH and VC. The cases with p53-positive SCC had a higher recurrence rate than p53-negative ones. Bcl-2 expression was negligible for all types of lesions. HPV-6/11 was detectable in 10% of dysplasia and 13% of SCC, but in neither VH nor VC. HPV-16/18, however, was consistently negative for all types of lesions. Our data suggest that p53, but not bcl-2, may play a role in tumor progression of BQ-related OELs, and that VH and VC are distinct and closely related histological lesions. The consistent absence of the malignant-type HPV in all BQ-related lesions suggests that HPV plays an insignificant role in the tumorigenesis of BQ-related oral cancers, although a cooperative role may exist between the benign-type HPV and BQ chewing., (Copyright 2002 S. Karger AG, Basel)