Examining factors associated with pre-admission to discharge of stroke patients.

Stroke is the second leading cause of death and a major cause of adult disability in Taiwan. This research established correlations between pre-admission and discharge data in stroke patients to promote education of the general public, prevention, treatment and high standards of chronic care. A total of 790 stroke patients at Chung Shan Medical University Hospital from 2007 to 2009 contained in the Taiwan Stroke Registry were included in this study. The patients were classified into two major categories: ischemic and hemorrhagic. Thirteen variables, including time series variables, were explored. Our results showed that age, education, hours from symptom onset to the emergency department (ED) arrival, and length of stay in hospital were significantly associated with stroke incidence. These findings show the present situation and medical quality of medical care for stroke patients in Taiwan. The factors association model may assist in developing a set of improvement plans for the coming year.

Quercetin-mediated cell cycle arrest and apoptosis involving activation of a caspase cascade through the mitochondrial pathway in human breast cancer MCF-7 cells.

Dietary polyphenols have been correlated with a reduced risk of developing cancer. Quercetin (a natural polyphenolic compound) induced apoptosis in many human cancer cell lines, including breast cancer MCF-7 cells. However, the involvement of possible signaling pathways and the roles of quercetin in apoptosis are still undefined. The purpose of this study was to investigate the effects of quercetin on the induction of the apoptotic pathway in human breast cancer MCF-7 cells. When MCF-7 cells were treated with quercetin for 24 and 48 h and at various doses (10-175 microM), cell viability decreased significantly in time- and dose-dependent manners. Exposure of MCF-7 cells to 10-175 microM quercetin resulted in an approximate 90.25% decrease in viable cells. To explicate the mechanism underlying the antiproliferative effect of quercetin, cell cycle distribution and apoptosis in MCF-7 cells was investigated after exposure to 150 microM quercetin for 6-48 h. Quercetin caused a remarkable increase in the number of S phase (14.56% to 61.35%) and sub-G1 phase cells (0.1% to 8.32%) in a dose- and time-dependent manner. Quercetin caused S phase arrest by decreasing the protein expression of CDK2, cyclins A and B while increasing the p53 and p57 proteins. Following incubation with quercetin for 48 h, MCF-7 cells showed apoptotic cell death by the decreased levels of Bcl-2 protein and DeltaPsi(m) and increased activations of caspase-6, -8 and -9. Moreover, quercetin increased the AIF protein released from mitochondria to nuclei and the GADD153 protein translocation from endoplasmic reticulum to the nuclei. These data suggested that quercetin may induce apoptosis by direct activation of the caspase cascade through the mitochondrial pathway in MCF-7 cells.

Prediction of KIT mutation in gastrointestinal stromal tumors by the immunoprofile of the tumor cells.

BACKGROUND/PURPOSE: Human KIT protooncogene is the cellular homolog of v-kit from the Hardy-Zuckerman 4 feline sarcoma virus, and encodes a 145-kDa type III tyrosine kinase growth factor receptor that is often mutated in gastrointestinal stromal tumors (GIST). Standardized mutation analysis is not available in many countries; therefore, we aimed to determine if the presence of KIT mutation in GIST can be predicted by the immunoprofile of the tumor cells. METHODS: One hundred and forty-nine GIST were subjected to mutation analysis for KIT and immunohistochemical analysis for the expression of CD117, CD34, alpha-smooth muscle actin (SMA), and S100 protein. Mutation and immunohistochemistry data were correlated. RESULTS: KIT mutation rates were higher in certain immunoprofile subsets of GIST than in GIST in general. Compared with the overall mutation rate of KIT (70%), all GIST with CD117+ and S100+ had > 80% probability of harboring mutated KIT, and the subset with additional CD34+ and SMA- had a mutation rate of 88%. The overall KIT mutation rate in CD117- GIST was 31%. However, the probability of KIT mutation in CD117- GIST with CD34+SMA+S100-, CD34-SMA-S100+, and CD34+SMA-S100+ was 100%, 100%, and 67%, respectively. Compared with the overall mutation rate (8.7%) of exon 9, GISTs with CD34+SMA+ had > or = 20% probability of harboring an exon 9 mutation, and all GISTs in the small intestine had a probability of 19%. CONCLUSION: When mutation analysis is not available, immunoprofiles based on CD117, CD34, SMA, and S100 can be used to predict the presence of KIT mutation, but it is less useful for the prediction of exon 9 mutation in GISTs.

Chronic kidney-disease screening service quality: questionnaire survey research evidence from Taichung City.

BACKGROUND: Chronic kidney disease (CKD) is a serious public health problem in Taiwan and the world. The most effective, affordable treatments involve early prevention/detection/intervention, requiring screening. Successfully implementing CKD programs requires good patient participation, affected by patient perceptions of screening service quality. Service quality improvements can help make such programs more successful. Thus, good tools for assessing service quality perceptions are important. AIM: to investigate using a modified SERVQUAL questionnaire in assessing patient expectations, perceptions, and loyalty towards kidney disease screening service quality. METHOD: 1595 kidney disease screening program patients in Taichung City were requested to complete and return a modified kidney disease screening SERVQUAL questionnaire. 1187 returned them. Incomplete ones (102) were culled and 1085 were chosen as effective for use. Paired t-tests, correlation tests, ANOVA, LSD test, and factor analysis identified the characteristics and factors of service quality. The paired t-test tested expectation score and perception score gaps. A structural equation modeling system examined satisfaction-based components' relationships. RESULTS: The effective response rate was 91.4%. Several methods verified validity. Cronbach's alpha on internal reliability was above 0.902. On patient satisfaction, expectation scores are high: 6.50 (0.82), but perception scores are significantly lower 6.14 (1.02). Older patients' perception scores are lower than younger patients'. Expectation and perception scores for patients with different types of jobs are significantly different. Patients higher on education have lower scores for expectation (r = -0.09) and perception (r = -0.26). Factor analysis identified three factors in the 22 item SERVQUAL form, which account for 80.8% of the total variance for the expectation scores and 86.9% of the total variance for the satisfaction scores. Expectation and perception score gaps in all 22 items are significant. The goodness-of-fit summary of the SEM results indicates that expectations and perceptions are positively correlated, perceptions and loyalty are positively correlated, but expectations and loyalty are not positively correlated. CONCLUSIONS: The results of this research suggest that the SERVQUAL instrument is a useful measurement tool in assessing and monitoring service quality in kidney disease screening services, enabling the staff to identify where service improvements are needed from the patients' perspectives.

Measuring patient's expectation and the perception of quality in LASIK services.

BACKGROUND: LASIK is the use of excimer lasers to treat therapeutic and refractive visual disorders, ranging from superficial scars to nearsightedness (myopia), and from astigmatism to farsightedness (hyperopia). The purposes of this study are to checking the applicability and psychometric properties of the SERVQUAL on Lasik surgery population. Second, use SEM methods to investigate the loyalty, perceptions and expectations relationship on LASIK surgery. METHODS: The method with which this study was conducted was questionnaire development. A total of 463 consecutive patients, attending LASIK surgery affiliated with Chung Shan Medical University Eye Center, enrolled in this study. All participants were asked to complete revised SERVQUAL questionnaires. Student t test, correlation test, and ANOVA and factor analyses were used to identify the characters and factors of service quality. Paired t test were used to test the gap between expectation and perception scores and structural equation modeling was used to examine relationships among satisfaction components. RESULTS: The effective response rate was 97.3%. Validity was verified by several methods and internal reliability Cronbach's alpha was > 0.958. The results from patient's scores were very high with an overall score of 6.41(0.66), expectations at 6.68(0.47), and perceptions at 6.51(0.57). The gap between expectations and perceptions was significant, however, (t = 6.08). Furthermore, there were significant differences in the expectation scores among the different jobs. Also, the results showed that the higher the education of the patient, the lower their perception score (r = -0.10). The factor loading results of factor analysis showed 5 factors of the 22 items of the SERVQUAL model. The 5 factors of perception explained 72.94% of the total variance there; and on expectations it explained 77.12% of the total variance of satisfaction scores.The goodness-of-fit summary, of structure equation modeling, showed trends in concept on expectations, perceptions, and loyalty. CONCLUSION: The results of this research appear to show that the SERVQUAL instrument is a useful measurement tool in assessing and monitoring service quality in LASIK service, and enabling staff to identify where improvements are needed, from the patients' perspective. There were service quality gaps in the reliability, assurance, and empathy. This study suggested that physicians should increase their discussions with patients; which has, of course, already been proven to be an effective way to increase patient's satisfaction with medical care, regardless of the procedure received.

Capsaicin-induced apoptosis in human breast cancer MCF-7 cells through caspase-independent pathway.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a significant pungent ingredient in a variety of red peppers of the genus Capsicum, is a type of vanilloid. It has been shown to exert biological activities (anticarcinogenic, antimutagenic and chemopreventive) in many cancer cell lines. It was found that capsaicin induces dose-dependent growth inhibition of MCF-7 cells, which does not express caspase-3. In this study, we investigated the molecular mechanism of capsaicin-induced apoptosis in MCF-7 cells. Treatment with capsaicin for 24 h resulted in dose-dependent apoptosis in these cells. After the addition of capsaicin, the levels of reactive oxygen species were reduced slightly in the earlier stage of treatment. Interestingly, an elevation of intracellular calcium ion concentration was detected in the MCF-7 cells. In time course and dosage studies, the mitochondrial membrane potential of MCF-7 cells decreased. However, the change was not significant. It is worth noting that the apoptosis-inducing factor translocated into the cytosol and nucleus from the mitochondria. Our results suggest that capsaicin induces cellular apoptosis through a caspase-independent pathway in MCF-7 cells, and that reactive oxygen species and intracellular calcium ion fluctuation has a minimal role in the process.

PIK3CA mutation occurs in nasopharyngeal carcinoma but does not significantly influence the disease-specific survival.

This study was aimed to test whether PIK3CA, BRAF and RAS are mutated in nasopharyngeal carcinomas (NPCs) and, if so, to further determine whether such mutations affect patients' survival. For this purpose, a total of 73 NPCs were subjected to mutational analyses for PIK3CA (exons 4, 7, 9, and 20), BRAF (codon 600), and RAS (codons 12, 13 and 61). Clinicopathological characteristics were correlated to the mutation data. Survival rates were compared with the log-rank test. The result showed that the mutation rate of PIK3CA in NPC (n = 73) was 9.6%, whereas both BRAF (n = 65) and RAS (n = 45) were wild type in every specimen with adequate DNA for analysis. PIK3CA mutation was slightly influenced by sex (P = 0.0418, Fisher's exact test), but had no significant relationship to other clinicopathological characteristics. Disease-specific survival was not significantly affected by PIK3CA mutations (P = 0.8825, log-rank test), albeit it was slightly better in younger patients (< or = 35 vs. >35 years of age) (P = 0.0477). These findings show that mutated PI3K may be involved in the NPC tumorigenesis but does not affect patient's prognosis, suggesting that PI3K is a potential target in NPC for targeted therapeutics using specific kinase inhibitors.

Plasma nuclear DNA and mitochondrial DNA as prognostic markers in corrosive injury patients.

STUDY OBJECTIVES: Ingestion of a corrosive substance produces an injury to the gastrointestinal tract and it is often difficult to evaluate the severity and prognosis of this injury. Increased concentrations of plasma nuclear DNA and mitochondrial DNA (mtDNA) have been found to be associated with the area of corrosion. This study examined the level of plasma DNA as it relates to the severity of corrosive injury. METHODS: Forty-eight consecutive patients were enrolled prospectively. The concentrations of plasma nuclear DNA and mtDNA were measured by real-time quantitative polymerase chain reaction assay at presentation to the emergency room and 12 h later. RESULT: The median age of the patients enrolled was 55 years (20 men and 28 women) with an overall mortality rate of 21%. Nineteen patients underwent operative intervention secondary to perforation. Findings included significantly elevated plasma nuclear DNA and mtDNA in the mortality group at presentation and 12 h after injury compared to the survival group. CONCLUSION: The concentrations of plasma nuclear DNA and mtDNA were elevated within 4 h after corrosive injury. The elevated concentrations of plasma nuclear DNA and mtDNA could be useful prognostic markers to correlate with the clinical outcome in corrosive patients.

A study on the personal traits and knowledge base of Taiwanese medical students following problem-based learning instructions.

INTRODUCTION: Problem-based learning (PBL), a pedagogic concept using a student-centred approach and problem-solving through small group discussions, has been adopted in varying degrees for years at all 11 medical institutes in Taiwan. Much evidence has shown that a number of factors can seriously affect student performance in PBL courses, such as the design of PBL scenarios, the tutors' character and students' attitudes and efforts. MATERIALS AND METHODS: The aim of this study was to examine how the personal characters or knowledge base of Taiwanese medical students influence their performance in a hybrid-PBL curriculum. A total of 309 (234 male, 75 female) high-school entry undergraduate medical students participated in this survey. Self-assessed personal traits were presented in a 44-item questionnaire with a Big Five factor structure. Knowledge base was assessed by students' score point average (SPA) based on their previous 4-year education in medical school. Peer-assessed performance of students in the PBL curriculum was carried out using a well-developed, reliable and validated evaluation form. RESULTS: Each student's peer-evaluated PBL performance can be divided into 5 principal components, which included control-lead, assist-coordinate, written organisation and compromise- comply (Eigen value >1). The consistency and reliability of the Big Five questionnaire on personal traits was analysed and discordant items were deleted (Cronbach's alpha = 0.72 to 0.86 after deletion). The relationship between the personal traits, knowledge base and PBL performance, as analysed by simple regression, showed that "extraversion" and "openness to experience" were positively related to the "assist-coordinate" characteristic in PBL performance, and "conscientiousness" was positively related to the "control-lead" characteristic in PBL performance. The SPA was positively related to the "assist-coordinate" or "control-lead" characteristic in PBL performance. The "agreeableness" was negatively correlated with the "control-lead" characteristic in PBL performance. After stepwise regression between the Big Five and each component of PBL performance, only the correlation between conscientiousness and control/lead, and between extraversion and assist/coordinate remained significant. CONCLUSION: Knowledge and personality characteristics appear to be associated with student performance in a hybrid-PBL curriculum. The implications of this study on the future development and application of this assessment tool in medical schools are presented.

Assessment of salivary function change in nasopharyngeal carcinoma treated by parotid-sparing radiotherapy.

PURPOSE: The purpose of this study was to evaluate function of major salivary glands, subjective xerostomia, and correlation between subjective and objective xerostomia scoring after precision-oriented radiotherapy for nasopharyngeal carcinoma. MATERIALS AND METHODS: From 2000 to 2002, 34 patients with histologically proven non-metastatic nasopharyngeal carcinoma received definitive therapy by parotid-sparing radiotherapy, which included intensity-modulated radiotherapy (33 patients>60 Gy), 3D-conformal radiotherapy, and brachytherapy boost. Salivary function was assessed by sialoscintigraphy pre-irradiation and post-irradiation at 1, 6, 12, and 18 months. The salivary stimulated secretion ratio (SSR) was used to evaluate function of submandibular and parotid glands. Subjective and objective xerostomia was monitored by the LENT/SOMA system. RESULTS: The median dose to parotid gland was 34.6 Gy (interquartile range, 32.9-36.5 Gy). The median dose to submandibular gland was 60.5 Gy (interquartile range, 58.1-61.5 Gy). Parotid-gland post-irradiation median SSR at 1 (0.01, P=0.000) and 6 (0.08, P=0.002) months showed significant reduction compared with pre-irradiation data (0.30). After 12 months, parotid-gland median SSR (12 months, 0.22, P = 0.734; 18 months, 0.16, P=0.885) lost significance compared with pre-irradiation data. Submandibular-gland post-irradiation median SSR at 1 (P=0.000), 6 (P=0.000), 12 (P=0.000), and 18 (P=0.000) months all showed significant reduction compared with pre-irradiation data. There were significant correlations between LENT/SOMA subjective and objective xerostomia scores at 6 months (r=0.657, P=0.000), 12 months (r=0.480, P=0.013), and 18 months (r=0.591, P=0.002). CONCLUSIONS: With parotid-sparing radiotherapy for nasopharyngeal carcinoma, gland function can recover significantly 12 months after radiotherapy. There were significant rank-order correlations between LENT/SOMA subjective and objective (analytic) grading scores at 6 to 18 months' follow-up.

Organ culture of the fetal mouse palate for screening the developmental toxicity of chemicals: a validation study.

Using in vitro organ culture of the fetal mouse palate in a chemically defined serumless medium, the toxicity of 24 chemical compounds was investigated. Explanted palates of day-12.5 mouse fetuses were exposed for 72 h in vitro to various concentrations of each chemical, and the fusion rate and growth parameters were compared between the experimental group and respective controls. The average rate of palate fusion was 84% in vehicle controls. For compounds that are teratogenic in experimental animals in vivo, the fusion rates of palatal shelves decreased as the concentration of the test chemicals increased, showing a dose-dependent relationship. Palate fusion was inhibited by 11 of the 15 in vivo teratogens, and the predictability of in vivo developmental toxicity in this culture system was 73%. Cyclophosphamide itself did not inhibit the growth and fusion of explanted palates, but supplementation of hepatic S-9 fraction and cofactors for a monooxygenase system converted it to a toxic substance, as was shown in other in vitro systems. The 50% inhibitory concentration (IC50) value calculated based on the fusion rate was also found to be a useful parameter for evaluating the developmental toxicity of drugs. The teratogenic risk in the human fetus could be assessed by comparing the minimal toxic concentrations of the test compound on cultured palates with the maximal plasma level in pregnant women under therapeutic conditions and with the plasma concentrations when its minimal teratogenic dose is given to pregnant mice. This organ culture system of the fetal palate should be useful for screening the developmental toxicity of drugs and other environmental agents, and its value should increase when it is used in combination with other battery test systems.

Palatal shelf movement during palatogenesis: a fate map of the fetal mouse palate cultured in vitro.

Day-13 fetal mouse palates (plug day=day 0) were labeled with carbon particles at various sites of palatal shelves and cultivated in a chemically defined medium for up to 48 h. During the culture period, the bilateral palatal shelves came in contact and fused with each other, which simulated in vivo palatogenesis. The carbon study revealed that at the midpalatal region, the medial edge of the palatal shelf elevated to the horizontal plane, elongated toward the midline, and made contact with the medial edge of the opposing shelf. On the other hand, near the anterior and posterior ends of the shelf, some new tissue was formed at the medial edge of the shelf by remodeling and this newly formed tissue took part in palatal fusion. The results of the present study indicate that during mouse palatogenesis, the anterior and posterior regions of the palatal shelf behave differently from the midpalatal region. It seems that in the fetal mouse palate, the midpalate closes mainly by means of rotation and medial elongation of the shelf, whereas the anterior and posterior parts of the palate close mainly by tissue remodeling of the medial edge and partly by medial elongation of the shelf.