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Chin-Fu Hsiao

Publications and source records attributed to Chin-Fu Hsiao.

33 records · Page 2Linked to original sources
PubMed2004

Physical inactivity is an important lifestyle determinant of insulin resistance in hypertensive patients.

The purpose of the study is to assess the relative impact of lifestyle factors including physical inactivity, cigarette smoking, and alcohol intake on insulin resistance in hypertensive patients. In total, 872 hypertensive patients, of Chinese and Japanese origin, from the Stanford Asia and Pacific Program for Hypertension and Insulin Resistance were included for the current analysis. Homeostasis model assessment for insulin resistance (HOMA-IR) and the insulin sensitivity index ISI0,120 were chosen as surrogate measures of insulin resistance. Standardized interview-administered questionnaires were used to obtain information on demographic and lifestyle characteristics. The sedentary hypertensive patients were more insulin resistant than the non-sedentary hypertensive. There were significant differences in Log (HOMA-IR) (0.06-unit increases, p < 0.01) and Log (ISI0,120) (0.05-unit decreases, p < 0.01) between sedentary and non-sedentary hypertensive patients after controlling demographic variables. There were no differences in insulin sensitivity in subjects with different smoking status. Neither smoking nor alcohol intake was persistently associated with insulin resistance in the analysis. Our results suggest that physical inactivity is an important lifestyle determinant of insulin resistance in hypertensive patients. The influences of smoking and alcohol intake on insulin resistance are less significant than physical inactivity in hypertensive subjects.

Adult↗
PubMed2004

A Bayesian noninferiority approach to evaluation of bridging studies.

A bridging study defined by The International Conference on Harmonization E5 is usually conducted in the new region only after the test product has been approved for commercial marketing in the original region due to its proven efficacy and safety. In this paper, we address the issue of analysis of clinical data generated by the bridging study conducted in the new region to evaluate the similarity for extrapolation of the foreign clinical data to the population of the new region. Information on efficacy, safety, dosage, and dose regimen of the original region cannot be concurrently obtained from the local bridging studies but are available in the trials conducted in the original region. A Bayesian noninferiority approach is therefore proposed to incorporate the data generated in the original region to evaluate bridging evidence by the local bridging studies and assess similarity between the new and original regions. Methods for sample size determination for the bridging study are also proposed.

Bayes Theorem↗
PubMed2003

Improved outcomes of HIV-1-infected adults with tuberculosis in the era of highly active antiretroviral therapy.

OBJECTIVES: To compare the survival and treatment responses to antiretroviral therapy between HIV-1-infected patients with active TB (TB patients) and without (non-TB patients) in the era of highly active antiretroviral therapy (HAART). DESIGN: 8-year prospective observational study at a university hospital. METHODS: A total of 125 (17.5%) TB patients (median CD4 cell count at TB diagnosis, 37 x 10(6) cells/l) and 591 non-TB patients (CD4 cell count at enrolment, 79 x 10(6) cells/l) were prospectively observed between June 1994 and October 2002. Virologic and immunologic responses were assessed in 230 antiretroviral-naive non-TB patients and 46 TB patients who concurrently initiated antituberculous therapy and HAART. The clinical outcome was evaluated by comparing incidence of new AIDS-associated opportunistic illnesses (OIs) and survival of all TB and non-TB patients. RESULTS Among antiretroviral-naive patients, CD4 cell count increase (71 versus 64 x 10(6) cells/l, P = 0.70) and proportions of patients achieving undetectable plasma viral load [20 of 46 versus 107 of 230, relative risk (RR), 0.93; 95% confidence interval (95% CI), 0.65-1.34; P = 0.71] at week 4 of HAART were similar between the 46 TB and 230 non-TB patients, as was the virologic failure during HAART (RR, 1.49; 95% CI, 0.92-2.41; P = 0.14). The risk for HIV progression to new OIs was also similar between the two groups (adjusted RR, 1.16; 95% CI, 0.764-1.77). The adjusted hazard ratio for death of TB patients compared with non-TB patients was 1.18 (95% CI, 0.65-2.32) before HAART era and 0.89 (95% CI, 0.57-1.69) in HAART era. CONCLUSIONS: Our data indicated that virologic, immunologic, and clinical responses to HAART and prognosis of HIV-1-infected TB patients who were concurrently treated with antituberculous therapy and HAART were similar to those of non-TB patients.

AIDS-Related Opportunistic Infections↗
PubMed2003

A group sequential approach to evaluation of bridging studies.

The International Conference on Harmonization (ICH) E5 guideline defines a bridging study as a supplementary study conducted in the new region to provide pharmacodynamic or clinical data on efficacy, safety, dosage, and dose regimen to allow extrapolation of the foreign clinical data to the population of the new region. Therefore, a bridging study is usually conducted in the new region only after the test product has been approved for commercial marketing in the original region due to its proven efficacy and safety. The issue of analysis of clinical data generated by the bridging study conducted in the new region to evaluate the similarity for extrapolation of the foreign clinical data to the population of the new region is the information on efficacy, safety, dosage, and dose regimen of the original region that cannot be concurrently obtained from the local bridging studies but is available in the trials conducted in the original region. A group sequential approach is therefore proposed to overcome the issue of internal validity. In particular, we use the region as a group sequence to enroll the patients from the original region first and then to enroll patients from the new region subsequently. Methods for sample size determination for the bridging study in the new region are also proposed.

Biopharmaceutics↗
PubMed2003

Correlation between bone mineral density and plasma lipids in Taiwan.

Many studies showed that depression is correlated with osteoporosis, while others showed that low cholesterol level is also related to depression. However, these relationships still remain controversial. Since the bone mineral density (BMD) is related to depression and depression is related to hypocholesterolemia, there might exist a correlation between BMD and plasma cholesterol levels. To prove this, we enrolled 5000 individuals, 2170 males, and 2830 females, who had health check-ups at a private clinic between 1998 and 1999. They were divided into three groups. Group 1 was composed of male subjects; Group 2, female subjects; and Group 3, females aged over 50 to exclude pre-menopausal females. Each subject had a routine physical examination, fasting blood drawing, BMD measured by dual energy x-ray absorptiometry (DEXA) over the wrist, and was given a questionnaire to answer. Between Groups 1 and 2, the females were significantly younger, had higher body mass index (BMI), total cholesterol (TC), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), and platelet, but lower BMD, fasting plasma glucose (FPG), triglycerides (TG), hemoglobin (Hgb), and white blood cell (WBC) count. As for Groups 1 and 3, all the aforementioned findings still remained the same except that the systolic blood pressure (SBP) was higher and diastolic blood pressure (DBP) was lower in Group 3. Our results showed that BMD is negatively related to age in males. In females, it is negatively correlated with age, FPG, PPG, SBP, DBP, TC, LDLC, TG, and Hgb, but positively related to BMI and platelet. However, for females in Group 3, BMD is only negatively related to age, FPG, SBP, and TG but positively related to BMI. Stepwise multiple regression analysis showed that the BMD is negatively related to age but positively related to BMI in both males and females. In Group 3, BMD is negatively related to age and FPG but positively related BMI. In conclusion, no correlation exists between BMD and cholesterol. This implies that the depression is not significantly related to cholesterol and/or BMD. This might be due to various confounding factors, which could affect their relationships. The negative correlation between BMD and FPG is only observed in females older than 50 years. Further studies are needed to clarify these relationships.

Blood Glucose↗
PubMed2003

Response to efavirenz plus two nucleoside reverse-transcriptase inhibitors in patients with advanced stage human immunodeficiency virus-1 infection in Taiwan.

From July 1, 1999 to April 30, 2002, 111 consecutive human immunodeficiency virus-infected, antiretroviral-naïve Taiwan patients initiated highly active antiretroviral therapy with efavirenz plus 2 nucleoside reverse-transcriptase inhibitors. Their median baseline CD4+ count was 50 x 10(6)/L (0-559 x 10(6)/L) and plasma viral load was 5.51 log10 copies/mL (3.09 to > 5.88 log10) as assessed by reverse-transcriptase polymerase chain reaction. Of the patients, 52.3% had a CD4+ count of < or = 50 x 10(6)/L, 74.8% had plasma viral load over 5 log10 copies/mL, and 58.5% had active AIDS-defining opportunistic illnesses. The median observation duration of antiretroviral therapy was 350 days (range, 28-991 days). At week 48 to 52 following the initiation of highly active antiretroviral therapy, 81. 8% (45/55) and 91.8% (45/49) of the patients achieved undetectable plasma viral load by intent-to-treat and ontreat analysis, respectively. At week 80 to 84, these percentage decreased to 69.7% (23/33) and 85.2% (23/27), respectively. Median CD4+ count increased from baseline to week 48 to 52 by 147 x 10(6)/L and to week 80 to 84 by 227 x 10(6)/L. The virologic and immunologic responses at each time period by intention-to-treat or on-treat analysis were similar between patients with baseline plasma viral load over or < or = 5 log10, CD4+ count over or < or = 50 x 10(6)/L, and with or without active AIDS-defining opportunistic illnesses. After initiation of highly active antiretroviral therapy for a median duration of 57 days (range, 2-638 days), 11 episodes of AIDS-defining and 11 non-AIDS opportunistic illnesses occurred. The results of this study suggest that efavirenz plus 2 nucleoside reverse-transcriptase inhibitors is a potent antiretroviral combination regardless of whether the patient has a high baseline plasma viral load, low CD4+ count, or AIDS-defining opportunistic illnesses.

Adult↗
PubMed2003

Fluconazole resistance rate of Candida species from different regions and hospital types in Taiwan.

From April 15 to June 15, 1999, 581 clinical Candida isolates from 19 hospitals in Taiwan were collected and susceptibilities to fluconazole of these isolates were determined by a broth microdilution method. A total of 42 (7.2%) isolates were resistant to fluconazole. Isolates from medical centers had a higher resistance rate to fluconazole than those from regional hospitals (10.7% vs 4.9%). Candida species isolated from different regions had different degrees of susceptibility to fluconazole. Approximately 2.5%, 6.5%, and 11.8% of Candida isolates from middle, north, and south regions, respectively, were resistant to fluconazole. The prevalence of the combination of Candida glabrata, Candida krusei, and Candida tropicalis infections were 44.5%, 49.8%, and 62.7% in middle, north, and south regions, respectively. There is an association between the rate of fluconazole resistance and the number of non-albicans Candida species collected from different regions and hospital types.

Academic Medical Centers↗
PubMed2002

Definition of three minimal deleted regions by comprehensive allelotyping and mutational screening of FHIT,p16(INK4A), and p19(ARF) genes in nasopharyngeal carcinoma.

BACKGROUND: Recurrent deletion on a chromosomal location in tumor cells can be detected by frequent allelic loss and generally is considered to be an indication of the existence of a tumor suppressor gene (TSG) in the region. In the current study, using fluorescent-labeled, high-density microsatellite markers for allelotyping, the authors pinpointed three minimal deleted regions (MDRs) and screened mutations of putative TSGs on chromosomes 3, 9, and 11 in nasopharyngeal carcinoma (NPC) cases occurring in Taiwan. METHODS: A total of 133 informative microsatellite markers were used on chromosomes 3, 9, and 11 with an average marker density of 4 centimorgans (cM) for the allelotyping of genomic DNAs isolated from NPC tissues and their corresponding lymphocytes in 48 patients. The correlation between allelic loss and the clinicopathologic parameters of NPC tissues was examined. In addition, putative TSGs including FHIT, p16(INK4a), and p19(ARF) were selected for mutation screening to investigate their potential participation in NPC tumorigenesis. RESULTS: Of 3787 informative allelotyping data, 25 frequent allelic losses (or loss of heterozygosity [LOH]) in 13 cytogenetic loci were identified based on a deletion frequency that was greater than the average of allelic loss on that particular chromosome. Several significant associations were determined after statistical analysis of the correlation between allelic loss and clinicopathologic parameters. The allelic losses by D9S318 and D11S1304 were associated with N2/N3 (P = 0.035 and P = 0.005, respectively), and those by D9S905 and D11S1304 were associated with grouped American Joint Committee on Cancer (AJCC) Stage III/IV samples (P = 0.022 and P = 0.017, respectively) of NPC tissues. In addition, three MDRs were revealed on 3p25.3-24.1 (< 19 cM), 3p23-21.31 (< 9 cM), and 11q22.1-23.2 (< 8 cM). To examine somatic mutations in previously reported TSGs located near these frequent LOH loci, three candidate genes, p16(INK4a), p19(ARF), and FHIT, were analyzed. Point mutations in the coding region of FHIT and in the intron 1 splicing acceptor site of both p16(INK4a) and p19(ARF) were detected in NPC cell lines. Sequence analysis of both p16(INK4a) and p19(ARF) transcripts revealed that the point mutation resulted in skipping of exon 2 and the generation of shorter transcripts. CONCLUSIONS: High-density allelotyping permitted the discovery of 3 MDRs on 3p25.3-24.1 (< 19 cM), 3p23-21.31 (< 9 cM), and 11q22.1-23.2 (< 8 cM) and a correlation was determined between allelic loss and clinicopathologic parameters of NPC tissues. More important, one somatic mutation in NPC cell lines on the intron 1/exon 2 splicing acceptor site of the INK4a/ARF locus was found to result in exon 2 skipping both p16(INK4a) and p19(ARF) transcripts, which presumably inactivates the functions of both the p16(INK4a) and p19(ARF) proteins.

Acid Anhydride Hydrolases↗
PubMed2002

Bayesian approach to evaluation of bridging studies.

We address the issue of analysis of clinical data generated by the bridging study conducted in the new region to evaluate the similarity for extrapolation of the foreign clinical data. A bridging study is usually conducted in the new region only after the test product is approved for commercial marketing in the original region due to its proven efficacy and safety. Sufficient information on efficacy, safety, dosage, and dose regimen has already generated in the original region. The empirical Bayesian approach is proposed to synthesize the data generated by the bridging study and foreign clinical data generated in the original region for assessment of similarity between the new and the original regions. A method for sample size determination for the bridging study is also suggested. It can be shown that the total sample size is inversely proportional to the strength of the evidence for the efficacy presented in the original region and the proportion of the patients assigned to receive the test product in the bridging study.

Algorithms↗
PubMed2002

Clustering and heritability of insulin resistance in Chinese and Japanese hypertensive families: a Stanford-Asian Pacific Program in Hypertension and Insulin Resistance sibling study.

The clustering between hypertension and other metabolic abnormalities related to insulin resistance syndrome (IRS) has been investigated in cross-sectional and prospective studies. Offspring studies have revealed that the clustering characteristics of IRS have familial components. However, it is not known whether the clustering also occurs in siblings (sibs) with different levels of blood pressure (BP). In addition, the genetic susceptibility accounting for the clustering in hypertensive families has not been determined. Siblings with Japanese or Chinese ancestry and having either similar BP levels (concordant sibs) or different BP levels (discordant sibs) were recruited. The delta method and variance component model were applied to analyze the differences in metabolic variables between hypertension (HTN) and low BP (LBP) sibs, and to compute the polygenic heritabilities for these metabolic variables and insulin sensitivity. After adjustment for age, gender and body mass index (BMI), HTN (n=393) sibs had higher levels of triglyceride (p < 0.0001), VLDL-cholesterol (p<0.0001), fasting insulin (p < 0.05), and homeostasis model assessment of insulin resistance (HOMAir) (p < 0.05) than LBP sibs (n = 389), but there were no differences in fasting glucose or high density lipoprotein (HDL)-cholesterol. The HTN sibs also had higher plasma glucose and insulin levels at 2 h after 75 g oral glucose loading (p<0.001 and p<0.01, respectively). The heritability estimates for fasting glucose, fasting insulin and HOMAir were 0.58, 0.43 and 0.46, respectively; for triglyceride, HDL-cholesterol, and BMI they were 0.60, 0.63 and 0.54, respectively. In hypertensive families, sibs with extreme levels of BP have significant differences in IRS-associated metabolic variables. The clustering characteristics and the significance of heritability estimation for these metabolic variables indicate that IRS is familial in nature and heritable in Chinese and Japanese hypertensive families.

Adult↗
PubMedDate not supplied

The insulin sensitivity, glucose sensitivity, and acute insulin response to glucose load in adolescent type 2 diabetes in Taiwanese.

BACKGROUND: Insulin sensitivity (SI), glucose sensitivity (SG), acute insulin response to glucose load (AIR), and obesity in adolescent type 2 diabetes patients (young diabetes, YDM) in Taiwan were studied. METHODS: Forty patients diagnosed at <22 years of age were enrolled and divided into non-obese (NOYDM, BMI < 27 kg/m(2)) and obese groups (OBYDM BMI > 27 kg/m(2)). Adult-onset type 2 diabetes patients (ADM) >40 years old (n = 41) and nondiabetic young adults (N) (n = 23) served as controls. Fasting plasma lipids, insulin, and glucose were measured. Homeostasis model assessment was calculated to estimate insulin sensitivity and beta-cell function. A frequent-sampled intravenous glucose tolerance test was performed to evaluate SI, SG, and AIR. RESULTS: SI and AIR were significantly lower in YDM and ADM than in N (0.92 +/- 0.13, 0.8 +/- 0.15 and 3.24 +/- 0.47 x 10(-4)/U/mL for SI; 40.3 +/- 20.3, 107.3 +/- 50.2, 1208 +/- 306.3 uU/min for AIR). SG of YDM and ADM were lower compared with N (0.014 +/- 0.00138, 0.0292 +/- 0.0058 vs 0.034 +/- 0.0086 min(-1) respectively). No difference was noted between YDM and ADM. SI and SG were not different in NOYDM and OBYDM. AIR was higher in OBYDM (83.6 +/- 34.3 vs -7.6 +/- 13.66 uU/min). CONCLUSIONS: YDM had defects in SI, SG, and AIR compared to N, which was similar to the pathophysiology of ADM. The results imply that YDM may be either a different subtype of diabetes or the same type of diabetes as ADM, with severe defects associated with earlier age of onset. OBYDM had higher AIR than NOYDM.

Adult↗
PubMedDate not supplied

Waist circumference predicts metabolic cardiovascular risk in postmenopausal Chinese women.

OBJECTIVE: The purpose of the study is to compare the differences in metabolic cardiovascular risk factors among postmenopausal Chinese women with or without abdominal obesity. DESIGN: The study is a cross-sectional, population-based, comparative cohort study. Each participant received anthropometric measurements and a 75-g oral glucose tolerance test after an overnight fast. The homeostasis model assessment for insulin resistance and the insulin sensitivity index, ISI, were used as measures of insulin resistance. A "metabolic cardiovascular risk score" was calculated from fasting insulin, glucose, lipids, and blood pressure. General linear models (GLM) were fit to examine the relation of waist circumference (WC) to insulin resistance and metabolic risk scores.(0,120). RESULTS: According to the International Obesity Task Force obesity criteria for Asians, 57 women had abdominal obesity (WC >/= 80 cm), and 58 had WCs less than 80 cm. The two groups were comparable in demographic variables and body mass index (BMI). The women with larger WCs were more insulin-resistant than their counterparts. The metabolic risk scores were significantly higher in women with abdominal obesity than in those without it. The results from the GLM showed that WC was an independent predictor of insulin resistance and metabolic risk scores after controlling for demographic variables (0.06- and 0.29-unit increases in homeostasis model assessment for insulin resistance and metabolic risk scores per 1 cm change in WC). Moreover, BMI neither correlated with metabolic risk scores nor affected the WC effects on insulin resistance and metabolic risk scores in the GLM. CONCLUSIONS: Postmenopausal Chinese women with abdominal obesity may carry higher metabolic cardiovascular risk than those without it. It is WC, not BMI, that predicts metabolic cardiovascular risk factors in these women.

Abdomen↗