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Biomedical subjects

C F Sun

Publications and source records attributed to C F Sun.

At least 19 recordsLinked to original sources

Molecular epidemiology of nalidixic acid-resistant campylobacter isolates from humans and poultry by pulsed-field gel electrophoresis and flagellin gene analysis.

To investigate the potential of poultry products as the source of human infections associated with quinolone-resistant campylobacters, 140 human and 75 poultry isolates of nalidixic acid-resistant campylobacters were collected between 1996 and 1998, and analysed by two molecular typing methods. By the analysis of restriction fragment length polymorphism of the flagellin gene, 33 distinct patterns were obtained, with 18 of which shared by both human (89%) and poultry (93%) isolates. By the pulsed-field gel electrophoresis of SmaI-restricted macrofragments, 105 different profiles were obtained, and 11 were found in both human (40%) and poultry (23%) isolates. When the two typing methods were combined, 112 unique genotypes were obtained, 11 of which were shared by both populations, including 53 (38%) human isolates and 14 (19%) poultry isolates. Although domestic poultry products are still important sources of the quinolone-resistant campylobacter infections in humans, there are other factors that might contribute to these increasing infections simultaneously. A more stringent policy in the use of antimicrobial agents in food animals can no longer be ignored.

Animals↗

Importance of hyperhomocysteinemia as a risk factor for venous thromboembolism in a Taiwanese population. A case-control study.

OBJECTIVE: To determine the current status of hyperhomocysteinemia, which is a known risk for venous thrombosis (DVT), in Taiwan. SUBJECTS: 101 unselected patients with a minimum of one episode of deep leg DVT, either initial inpatients or current compliant outpatients in a teaching hospital. METHODS: Various thrombophilic risks, gene polymorphism and clinical predisposition were evaluated. RESULTS AND CONCLUSIONS: Patients presented higher fast total plasma homocysteine (hcy) levels than age- and sex-matched controls did (14.1 vs. 9.94 microM). Based on the 95th percentile of control values, hyperhomocysteinemia had a four- to nine-fold risk for DVT, irrespective of clinical predisposition, as well as other thrombophilic risks surveyed. Polymorphism of a metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR), was not associated with DVT, although homozygous thermolabile mutation tended to have higher plasma hcy levels. Factor V Leiden was absent in analysis of 80 patients. In complete evaluation (hcy, antithrombin (AT), protein S (PS), protein C (PC), lupus anticoagulant (LA), anticardiolipin antibody) of a subset of 83 patients hyperhomocysteinemia was the most prevalent risk (33.7%), with PC or PS deficiencies following (22.9%). Thus, hyperhomocysteinemia is a prominent risk for DVT in Taiwan.

Adult↗

Development of two ELISA for estrogen and progesterone receptor with sufficient sensitivity for fine needle aspirate and core biopsy.

The quantitative determination of estrogen and progesterone receptors (PR and ER) in breast tumor cytosol has been routinely performed in clinical laboratories to aid in the selection between hormonal and chemotherapy and also to predict prognosis. However, the small amount of tissue available from the increasingly popular fine-needle aspiration and core biopsies from breast cancer patients requires more sensitive immunoassays for receptor quantification. We have developed two sensitive immuno-assays for ER and PR on microplate with the use of recently available anti-ER and anti-PR antibodies of higher affinity and a powerful signal magnification agent, namely Amdex. The calibrator was a pooled breast tumor cytosol used as calibrator and calibrated against Abbott kits. The protein concentration of the cytosol and the upper normal cutoffs for our assays were reduced to approximately 0.2 mg/mL and 3 fmol/0.2 mg/mL, respectively. Both assays have sensitivities close to 1 fmol/mL, which are sufficiently sensitive for the receptor quantification in fine-needle aspiration biopsies and cord biopsies of breast tumor.

Antibodies, Monoclonal↗

Characterization of serum and urinary chromogranin A by size exclusion chromatography: impact on calibrator selection and urinary assay.

Serum chromogranin A (CgA) is a useful marker for neuroendocrine tumors and is detectable in carcinomas at advanced stages. Elevated serum CgA is also an indicator of poor prognosis in prostate cancer and is useful for predicting the failure of hormonal therapy for prostate cancer patients. We found that CgA molecules with three different sizes could be detected in normal human serum. However, only the largest CgA molecule appears in patients with liver disease. Serum taken from cancer patients is composed predominantly of the middle-sized molecule, whereas the smallest CgA molecule was elevated in serum drawn from renal patients. Moreover, only the smallest CgA molecule was found in urine. We believe that the largest CgA molecule is metabolized by the liver, whereas the smallest CgA molecule is removed from the blood circulation via the kidney. Because the medium-sized CgA is the dominant molecule in both the cell medium of the tumor cell line SK-N-AS and sera from patients with malignant diseases, CgA from the cell medium was selected as the calibrator for the CgA ELISA assay. Our findings also suggest that it would not be possible to measure the urinary CgA to reflect the serum CgA concentration in order to detect pheochromocytoma among patients with hypertension.

Calibration↗

Secular trends in incidence and antimicrobial resistance among clinical isolates of Salmonella at a university hospital in Taiwan, 1983-1999.

The incidence and antimicrobial resistance among clinical isolates of salmonella at a university hospital in Taiwan between 1983 and 1999 are summarized in this report. A total of 7986 isolates were analysed. Serogroup B has been the most prevalent over the years, with an apparently continuous decline after 1995. Concordant decrease was also found among S. choleraesuis and S. typhi isolates in recent years. In contrast, the proportion of serogroup D strains increased significantly after 1996. S. typhi remained relatively susceptible to most of the antimicrobial agents examined. For non-typhoidal isolates, antimicrobial resistance to ampicillin (62%), chloramphenicol (67%), and sulfamethoxazole-trimethoprim (37%) was relatively higher than that reported elsewhere. Newer generation cephalosporins and fluoroquinolones remained effective over the years, although emerging resistance to these drugs has been noticed since 1992. A more prudent selection and use of antimicrobial agents, in both humans and animals, and a continuous surveillance of resistance are essential in the future.

Drug Resistance, Microbial↗

Real-time quantitative PCR analysis for alpha-thalassemia-1 of Southeast Asian type deletion in Taiwan.

Since homozygosity of the alpha-thalassemia-1 of Southeast Asian (SEA) type deletion results in hydrops fetalis, a novel protocol based on the real-time quantitating polymerase chain reaction (PCR) technique has been developed to quantify the intact and aberrant alpha-globin genes in adults. The ratio of the normal/SEA-bearing alpha-globin genes was expressed in cycle threshold (C(T)) values. Theoretically, a relative ratio of one to one was anticipated in individuals carrying the SEA type deletion. Twenty-five heterozygous and 20 normal cases were analyzed retrospectively with this protocol. Data showed that the CT values for the intact alpha-globin gene allele and the allele bearing the SEA type deletion in carriers were 28.74+/-1.49 and 26.46+/-2.05, respectively. Therefore, the ratio of normal/SEA type deletion-bearing alpha-globin genes in the carriers was 1.09+/-0.043. No ambiguous results were observed from other less common genotypes associated with alpha-thalassemia, such as the Philippine type deletion. Based on the results, we concluded that this protocol could provide a rapid method to mass screen carriers with alpha-thalassemia-1 of SEA type deletion in this region.

Alleles↗

Search for immunomodulatory effects of blood transfusion in gastric cancer patients: flow cytometry of Th1/Th2 cells in peripheral blood.

Allogeneic transfusion seems to drive the immune system toward a Th2 response and away from a Th1 response, providing a hypothetical mechanism for transfusion-induced immunomodulation. By means of an intracytoplasmic cytokine detection technique with flow cytometry, it is possible to measure Th1 and Th2 cells derived from peripheral blood mononuclear cells. This study evaluated the presence of transfusion-induced immunomodulation in 11 gastric cancer patients after gastrectomy with perioperative blood transfusion, compared to 11 gastric cancer patients who were treated by gastrectomy without transfusion. Lymphocytes subsets, including CD4 T cells, CD8 T cells, CD4/CD8 Ratio, CD2(+) T cells, CD3(+) T cells, and CD19(+) B cells, were measured in these patients, as well as variables that might suggest transfusion-induced immunomodulation, such as duration of antibiotic use, duration of hospital stay, and total hospital charges. This study also measured changes in the Th1/Th2 ratio. Th1 and Th2 lymphocytes were characterized by measuring intracellular expression of cytokines with flow cytometry. Cells were stimulated with phorbol myristate acetate and ionomycin in the presence of brefeldin-A. The results showed no significant differences in lymphocyte subsets, Th1/Th2 ratio, total hospital charges, or duration of antibiotic utilization between the groups of transfused and non-transfused gastric cancer patients after gastrectomy. The only significant difference was a longer hospital stay for transfused patients (mean 20.5 da) compared to non-transfused patients (mean 16.2 da). The anticipated finding of a Th2 response after blood transfusion was not observed. A larger group of patients may be needed to document such an effect, since many confounding variables affect the morbidity and outcome of surgery in these patients.

Aged↗

Outbreaks of nosocomial bloodstream infections associated with multiresistant Klebsiella pneumoniae in a pediatric intensive care unit.

BACKGROUND: Between June and October 1997, and during April 1998, a cluster of nosocomial bloodstream infections (BSIs) associated with Klebsiella pneumoniae was observed in 8 premature neonates from 1 pediatric intensive care unit (TPICU) in a 4000-bed medical center in northern Taiwan. An investigation was conducted to identify the possible reservoirs and mode of transmission. METHODS: Epidemiologic surveillance and infection control interventions were executed. The environment was checked by submitting several swab samples for microbiological studies. The antibiograms and results from 2 molecular typing methods (pulsed-field gel electrophoresis and infrequent-restriction site polymerase chain reaction) of all bacteremic and environmental isolates of K. pneumoniae were compared. RESULTS: Totally 39 K. pneumoniae isolates, including 9 from bacteremia, 26 from the environment, and 4 controls, were analyzed. One major pattern was found in 21 isolates, which included 8 bacteremic isolates with identical antibiograms, a single isolate from rectal swab screening, 2 of 8 isolates from hand cultures of medical staff, and 10 of 17 isolates from swabs of sinks in the TPICU. All 21 isolates illustrated identical antibiograms, while the other 18 isolates shared 4 antibiograms and 15 unique patterns. CONCLUSIONS: The nosocomial BSIs appeared to be an outbreak induced by 1 multiresistant K. pneumoniae strain. The sinks may have acted as reservoirs for this outbreak strain. During washing, splattered water droplets containing the bacterial particles may have contaminated the hands of medical personnel and were then further transmitted to patients.

Bacteremia↗

Non-radioactive Southern hybridization for early diagnosis of alpha-thalassemia with southeast Asian-type deletion in Taiwan.

Alpha-thalassemia has been estimated to account for over 60% of hydrops fetalis cases in Taiwan. The most common genotypic lesion found in alpha-thalassemia-1 cases in Taiwan is deletion of a large segment of the alpha-globin gene cluster, termed the Southeast Asian-type deletion (-SEA/; further referred to as SEA-type deletion). Seven chorionic villus samples (CVS) from pregnancies of couples both heterozygous for SEA-type deletion were studied. Non-radioactive Southern-blot hybridization using the dig-alkaline phosphatase detection system was developed to fulfill this purpose. The results were compared with corresponding polymerase chain reaction (PCR) data to elucidate the effectiveness of these two protocols in the diagnosis of the SEA-type deletion. The data showed that of the seven CVS, three demonstrated a distinctive band pattern, indicating their homozygous status of SEA-type deletion, whereas two showed heterozygous patterns, and the other two were free of the deletion. Homozygosity of the deletion was confirmed by Southern-blot hybridization performed on DNA samples extracted from the abortus tissue. However, two of the three cases with SEA-type deletion showed heterozygous PCR results. Maternal cell contamination could be responsible for the artifacts in the PCR results, but the influence due to the contamination is minimal in non-radioactive Southern-blot hybridization. We concluded that PCR is suitable for screening of carrier adults with SEA-type deletion, and non-radioactive Southern hybridization is ideal for early prenatal diagnosis of the SEA-type deletion.

Asia, Southeastern↗

Molecular investigation of two clusters of hospital-acquired bacteraemia caused by multi-resistant Klebsiella pneumoniae using pulsed-field gel electrophoresis and in frequent restriction site PCR. Infection Control Group.

Two molecular typing methods, DNA macrorestriction analysis with XbaI resolved by pulsed-field gel electrophoresis (PFGE) and infrequent restriction site PCR (IRS-PCR) assay with adapters designed for XbaI and HhaI restriction sites, were used to investigate two clusters of hospital-acquired bacteraemia associated with multi-resistant Klebsiella pneumoniae which occurred in a paediatric intensive care unit (PICU). A total of 56 K. pneumoniae isolates were analysed. These included 10 bacteraemic isolates from eight patients, 26 isolates obtained during an epidemiological survey, and 20 epidemiologically non-related isolates incorporated as controls. One major pattern was demonstrated in 22 of the 56 isolates analysed. These included nine of the 10 bacteraemic isolates, a single rectal isolate, two hand culture isolates and 10 sink isolates. All of these 22 isolates illustrated identical antibiograms, whilst the other 34 isolates shared six antibiograms and 31 unique patterns by either PFGE or IRS-PCR assay. The two clusters of bacteraemia appeared to be outbreaks induced by the same strain of K. pneumoniae which may have utilized sinks as reservoirs and been transmitted through the hands of medical personnel to patients. IRS-PCR demonstrates concordant results with PFGE analysis in studying the genetic relationships among K. pneumoniae isolates, and serves as an excellent epidemiological tool for this bacterium.

Bacteremia↗

Elevated serum chromogranin A is detectable in patients with carcinomas at advanced disease stages.

Chromogranin A (CgA), a marker of neuroendocrine cells and an indicator for neuroendocrine differentiation, is associated with a poor prognosis when detected in tumor tissue, based on immunohistochemical techniques. We sought to determine whether it is possible to detect elevated serum CgA in patients with commonly occurring carcinomas of non-neuroendocrine origin. CgA was measured in both random and serial serum specimens, using a serum CgA assay developed in our laboratory. Elevated levels of serum CgA were detected in patients with carcinoma of the prostate, breast, ovary, pancreas, and colon. Serum CgA levels in patients with all types of carcinoma appeared to parallel the changes of serum dominant tumor markers and were found in sera containing highly elevated tumor markers. Based on these preliminary findings, perhaps we should monitor CgA, in addition to the routinely used tumor markers, during the treatment of patients with carcinomas to determine if CgA is useful as a prognostic marker in carcinomas other than prostatic cancer.

Biomarkers, Tumor↗

DNA polymorphism of Mycobacterium abscessus analyzed by infrequent-restriction-site polymerase chain reaction.

BACKGROUND: Mycobacterium abscessus is an important pathogen that has been increasingly associated with many clinical and nosocomial infections. A reliable molecular typing scheme is essential for the epidemiological study of this rapidly growing mycobacterium. Pulsed-field gel electrophoresis (PFGE), considered to be the gold standard among molecular typing methods, has failed to provide satisfactory results in the molecular typing of this bacterium. A newly developed molecular typing method, infrequent-restriction-site polymerase chain reaction (IRS-PCR), was examined in this study to determine its suitability for fingerprinting M. abscessus isolates. METHODS: Eight clinical isolates of M. abscessus and two reference strains (M. abscessus ATCC 19977 and M. chelonae ATCC 35749) were studied by DNA macrorestriction analysis with XbaI resolved by PFGE, and IRS-PCR assay with adaptors designed for XbaI and HhaI restriction sites. RESULTS: By PFGE, different banding patterns were found in two clinical isolates of M. abscessus; the other isolates yielded only broken DNA and could not be assessed. By IRS-PCR, unique patterns were noted for the 10 isolates; the 10 appeared to be genetically different. CONCLUSION: IRS-PCR may be an efficient substitute for PFGE in analyzing the DNA polymorphism and epidemiology of M. abscessus.

Electrophoresis, Gel, Pulsed-Field↗

Novel mutations, including a novel G659A missense mutation, of the FUT1 gene are responsible for the para-Bombay phenotype.

Para-Bombay phenotype, with an estimated incidence of 1 in 8000 in Taiwanese residents based on serological analysis, is caused by aberrant alpha(1,2)-fucosyltransferase function and hence diminished H-antigen synthesis. In an individual with para-Bombay phenotype, DNA sequencing revealed two missense mutations previously reported C658T mutation and a novel G659A mutation. Haplotype analysis with restriction enzyme digestion showed that the two mutations are located on opposing alleles of the H (FUT1) gene and lead to compound heterozygosity. Since no other known genetic changes were evident, it appears that the new missense mutation, G659A, is deleterious to the alpha(1,2)-fucosyltransferase function encoded by the H (FUT1) gene.

ABO Blood-Group System↗

Genetic variation at nine STR loci in populations from the Philippines and Thailand living in Taiwan.

In order to apply a set of nine STR loci and the amelogenin locus in forensic testing, we have performed a population study on individuals from the Philippines and Thailand living in Taiwan (273 Philippine and 146 Thai individuals were typed by commercially available kits and an automated sequencer). A total of 73 alleles for all systems for both populations could be observed in these two populations. No new intermediate fragments were found. Allele frequencies showed no deviation from Hardy-Weinberg equilibrium. The mean exclusion power (MEP) ranged from 0.327 (TPOX) to 0.706 (FGA), the discriminating power (DP) ranged from 0.790 (TPOX) to 0.963 (FGA) for Philippinos, MEP ranged from 0.247 (TPOX) to 0.723 (FGA), DP ranged from 0.761 (TPOX) to 0.968 (FGA) for Thais, the combined MEP is > 0.9988 and the combined DP is > 0.9999999993 for both Philippinos and Thais.

Alleles↗

Different patterns of serum chromogranin A in patients with prostate cancer with and without undergoing hormonal therapy.

Elevated serum chromogranin A (CgA) levels have been detected in patients with prostate cancer who have developed resistance to hormonal therapy. We would like to reexamine these cases by using serial specimens to determine whether such elevated levels are also detectable in prostate cancer patients not undergoing hormonal therapy. Serum CgA was measured in both random and serial specimens from prostate cancer patients with and without undergoing hormonal therapy. We found that serum CgA levels became elevated much earlier than did the levels of serum PSA in approximately one-third of prostate cancer patients developing resistance to hormonal therapy. On the other hand, serum CgA levels became elevated at later, more advanced stages of the disease in patients not undergoing hormonal therapy. Elevated serum CgA levels were usually detected in specimens containing highly elevated PSA. The early rise of serum CgA levels provides an early signal allowing a change of therapy to be made before the disease progresses to a fatal stage. Drugs targeting neuroendocrine cells should be considered for prostate cancer patients with elevated serum CgA levels.

Antineoplastic Agents, Hormonal↗

Development of a microplate assay for serum chromogranin A (CgA): establishment of normal reference values and detection of elevated CgA in malignant diseases.

Chromogranin A (CgA), a marker for neuroendocrine cells, is associated with poor prognosis when detected by immunohistochemical technique in prostate tumors. We have developed an ELISA on microplates for serum CgA and established the normal reference range. We also attempted to find out whether elevated serum CgA levels could be found in patients with various malignant diseases. Because of non-Gaussian distribution, both medians and 97.5 percentiles of serum CgA levels for men and women of four different age groups were determined. For women, the median and 97.5 percentiles are 20.7 and 63.9 ng/mL for ages 20 to 50, and 32 and 93.8 for 50 to 80 years of age, respectively; for men, they are 27.9 and 78.4 ng/mL for ages 18 to 40 and 41.6 and 92 for 40 to 80 years old, respectively. Elevated serum concentrations of CgA were detectable in patients with prostate cancer not undergoing hormonal treatment, and in patients with various malignant diseases including nonendocrine carcinomas. Most elevated serum CgA levels were associated with sera containing highly elevated serum tumor markers. Drugs targeting neuroendocrine cells should be administered for cancer patients with elevated serum CgA levels.

Adult↗

Bone marrow failure and myelofibrosis in a case of PVP storage disease.

"PVP storage disease" is a disorder occurring in patients who have received high molecular weight polyvinylpyrrolidone (PVP), which cannot be excreted from the body. These large polymers deposit in the histiocytes and cause proliferation and infiltration of histiocytes in the reticuloendothelial system. There was usually no significant damage to these organs except that prolonged administration might cause bone destruction, skin lesions, arthritis, and polyneuropathy. We describe a patient who had received a large amount of PVP-containing solution for years. Severe bone marrow failure with extensive infiltration of bone marrow by foamy histiocytes occurred later. In addition, she suffered from multiple pathological fractures with spinal cord compression and arthritis of bilateral knee joints.

Adult↗

Prognostic factors in node-negative breast cancer patients: the experience in Taiwan.

BACKGROUND: Adjuvant chemotherapy has improved the length of disease-free survival and overall survival in node-negative breast cancer patients. It has been a common practice to select only the patients with higher rates of recurrence for adjuvant therapy. Therefore, it is essential to define the risk factors in node-negative breast cancer patients. MATERIALS AND METHODS: Two hundred fifty-five patients with axillary node-negative breast cancers without adjuvant chemotherapy or hormonal therapy at Chang Gung Memorial Hospital between 1981 and 1986 were included in this study. Tissue blocks for DNA flow cytometry study was available in the tumors of 145 patients. RESULTS: The median follow-up period was 121 months and the percentages of patients with 10 years of disease-free survival (DFS) and overall survival (OS) were 75.1% and 82.2%, respectively. The significant poor prognostic factors for 10 years of OS were a tumor size larger than 3 cm, negative estrogen and progesterone receptor status, and having a non-diploid tumor (p value = 0.0176, 0.048 and 0.016, respectively). The patients with frozen section, high mitotic rate, and Scarff-Blood-Richardson (SBR) grade II and III tumors had a worse prognosis than the others, but this trend did not reach statistical significance. The patients with positive estrogen receptor status had a 10-year disease-free rate (DFR) of 94%, and these with tumors less than 2 cm plus SBR grade I had a 10-year DFR of 92%. CONCLUSION: The node-negative breast cancer patients with a low risk of recurrence were those who had estrogen receptor positive, tumor less than 2 cm with SBR grade I, and intraductal carcinomas. Adjuvant chemotherapy would be no benefit for these patients.

Adult↗