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Biomedical subjects

Chin-Fu Hsiao

Publications and source records attributed to Chin-Fu Hsiao.

At least 19 recordsLinked to original sources

Clonality and prognostic implications of p53 and epidermal growth factor receptor somatic aberrations in multiple primary lung cancers.

PURPOSE: For treatment decision and prognostic applications, we evaluated p53/epidermal growth factor receptor (EGFR) somatic aberrations in multiple primary lung cancers to differentiate multifocal tumors from intrapulmonary metastasis. EXPERIMENTAL DESIGN: Fifty-eight multiple primary lung cancers of 1,037 patients in a 10-year period were identified to investigate somatic mutations and altered expression of p53 and EGFR for clonality assessment. Genomic DNA was extracted from microdissected cells of paraffin-embedded multiple primary lung cancer tissues. Overexpression and somatic mutations in exons of p53 (exons 5-8) and tyrosine kinase domain of EGFR (exons 18-22) were examined by immunohistochemical staining and DNA sequencing, respectively. RESULTS: High frequency of somatic mutations in p53 (33 of 58, 56.9%) and/or EGFR (44 of 58, 75.9%) resulted in high discrimination rate of tumor clonality (50 of 58, 86.2%) of multiple primary lung cancers. Twenty-two cases (37.9%) were assessed as having the same clonality and 28 cases (48.3%) were determined as having different clonality, which further supported the carcinogenic theory of field cancerization. Notably, the occurrence of lymph node metastasis was more commonly observed in tumors with the same clonality (P = 0.045) and was associated with poor patient 5-year survival rate (P = 0.001). However, no correlation was found between tumor clonality and patient survival (P = 0.630). The EGFR somatic aberrations in 58 multiple primary lung cancers, including vascular invasion associated with EGFR overexpression (P = 0.012) and mutation (P = 0.025), further suggested the potential benefits of target therapy of inoperable multiple primary lung cancers. CONCLUSIONS: Our results suggest that analysis of somatic alterations in p53 and EGFR can significantly improve the clonality assessment and impact management of multiple primary lung cancer patients.

DNA Mutational Analysis↗

Use of prior information for Bayesian evaluation of bridging studies.

The 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 based on 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 available in the trials conducted in the original region. Liu et al. (2002) have proposed a Bayesian approach to synthesize the data generated by the bridging study and foreign clinical data generated in the original region for assessment of similarity based on superior efficacy of the test product over a placebo control. However, the results of the bridging studies using their approach will be overwhelmingly dominated by the results of the original region due to an imbalance of sample sizes between the regions. Therefore, in this paper we propose a Bayesian approach with the use of a mixture prior for assessment of similarity between the new and original region based on the concept of positive treatment effect. Methods for sample size determination for the bridging study are also proposed. Numerical examples illustrate applications of the proposed procedures in different scenarios.

Algorithms↗

Genome-wide linkage analysis of lipids in nondiabetic Chinese and Japanese from the SAPPHIRe family study.

BACKGROUND: Lipid levels are recognized as major risk factors for coronary heart disease (CHD). Discovery of major loci underlying quantitative lipid traits could help to elucidate the genetics of CHD. METHODS: We performed a genome-wide search for quantitative trait loci linked to lipid phenotypes in 1538 Chinese subjects (509 families) and 625 Japanese subjects (204 families) not taking lipid-lowering medications from the Stanford-Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) study. The multipoint variance-components method was used to test for linkage between marker loci and each trait by maximum likelihood methods adjusted for effects of age, age(2), gender, body mass index (BMI), smoking, alcohol drinking, physical activity, and field center. RESULTS: The highest logarithm of odds (LOD) score detected was 3.22 for logarithmically transformed HDL-cholesterol on chromosome 12 at 113 cM in Chinese subjects. This score overlaps the positive findings for HDL reported in Mexican Americans (chromosome 12 at 96 cM). Although no strong evidence for linkage was found in Japanese subjects, some modest peaks (LOD score >==1.5) were found in several regions that have been reported in other published genome scans. For example, the Japanese SAPPHIRe peak for HDL (chromosome 1 at 167 cM; LOD = 1.54) was very close to the quantitative trait loci (QTL) for HDL reported in the scan of white American HyperGEN (chromosome 1 at 159.9 cM). CONCLUSIONS: Genome-wide scan for genes influencing lipid phenotypes was conducted and we found significant linkage of HDL to a locus on chromosome 12 in Chinese subjects and no linkage signal exceeding 1.68 was found in the Japanese subjects.

Adult↗

Higher seroprevalence of Entamoeba histolytica infection is associated with human immunodeficiency virus type 1 infection in Taiwan.

We assessed the seroprevalence of Entamoeba histolytica infection using indirect hemagglutination antibody (IHA) assay among 667 HIV-infected persons (group A), 1,311 asymptomatic HIV-uninfected persons seeking anonymous HIV testing (group B), 616 HIV-uninfected controls with gastrointestinal symptoms (diarrhea and/or liver abscess) seeking medical care (group C), and 2,500 healthy controls undergoing health check-up (group D). An IHA titer >or= 128 was detected in 7.1% of group A, 2.5% of group B, 1.8% of group C, and 0.1% of group D (P < 0.0001). The highest seroprevalence (11.2%) was noted among HIV-infected persons who were men having sex with men (MSM) 30-39 years of age. Compared with persons with gastrointestinal symptoms, the adjusted odds ratio for having high IHA titers among HIV-infected persons was 3.206 (95% confidence interval, 1.433, 7.176; P = 0.005). These findings show that HIV-infected persons, especially MSM 30-39 years of age, are at significantly higher risk of E. histolytica infection.

Adolescent↗

Improved survival of persons with human immunodeficiency virus type 1 infection in the era of highly active antiretroviral therapy in Taiwan.

We assessed the survival of 1,044 HIV-infected persons enrolled in three periods: period 1, 1994 to 1997 (before the introduction of highly active antiretroviral therapy [HAART]); period 2, 1997 to 2000 (early-HAART); and period 3, 2000 to 2004 (late-HAART). As of 30 June 2005, 259 (24.8%) persons had died after a median observation duration of 985 days (range, 2 - 4,025 days). The mortality rate declined from 33.75 per 100 person-years in the pre-HAART era to 6.51 per 100 person-years in the late-HAART era (P < 0.0001). The adjusted hazard ratios for death in persons with a baseline CD4 count of <200 cells/mul in periods 2 and 3 were 0.605 (P = 0.007) and 0.371 (P < 0.0001), respectively, when compared with persons enrolled in period 1; the adjusted hazard ratio for death was 0.611 for persons enrolled in period 3 when compared to period 2 (P = 0.01). Our study suggested that the survival of persons in the late stage of HIV infection in Taiwan continued to improve in the late HAART era.

Adolescent↗

Changes in the clinical spectrum of opportunistic illnesses in persons with HIV infection in Taiwan in the era of highly active antiretroviral therapy.

We compared changes in the relative frequencies of opportunistic illnesses (OIs) among 1,044 Taiwanese persons with HIV infection who were enrolled in three study periods from June 1994 to June 2004: before the introduction of highly active antiretroviral therapy (HAART); early HAART; and late HAART. Nearly two-thirds of those newly diagnosed with HIV infection had CD4 counts below 200/mm(3). Among a total of 1,182 OIs, candidiasis, Pneumocystis carinii pneumonia, and tuberculosis were the most common in all three study periods within 3 months after enrollment. Within 3 to 12 months after enrollment, the number of OIs declined significantly. Only 81 cases of OIs were diagnosed, the most common of which were cytomegalovirus disease, tuberculosis, candidiasis, and Mycobacterium avium complex infection. Except for the decreasing frequency of Kaposi's sarcoma, there was no significant change in the relative frequency of each individual OI within 3 months and within 3-12 months after enrollment across the three study periods. We concluded that despite the significant decrease in the number of AIDS-related OIs, the relative frequencies of common OIs did not change significantly after the introduction of HAART.

AIDS-Related Opportunistic Infections↗

Genomewide loss of heterozygosity and its clinical associations in non small cell lung cancer.

We extensively allelotyped a panel of 71 microdissected primary surgically resected non small cell lung cancer (NSCLC) tumors to identify chromosomal regions that are likely to contain tumor suppressor genes (TSGs) or associated with clinicopathologic and prognostic effects. Loss of heterozygosity (LOH) was detected by genotyping of 177 microsatellite markers and correlation of LOH with clinicopathologic parameters and prognosis was analyzed. Twenty markers showed an LOH frequency greater than 48%, and 8 of them (2p23.3, 2p24.3, 2q35, 6p22.2, 7p14.3, 7p22.2, 17q24.3 and 21q22.3) were novel in NSCLC. The high LOH regions were confirmed by further aligning continuous LOH regions from another set of 24 NSCLC tissues and defining 7 minimal deletion regions ranging from 1.29 to 12.26 cM. The aberrations of 8 markers showed a significant correlation with alteration of p16 and Rb proteins, suggesting the gene(s) located in the chromosomal loss that may interact with p16/Rb pathway. In addition, markers specifically associated with smoking, histology types and tumor stages were identified and the linked candidate TSGs were suggested. For example, marker D1S1612 closely linked with Mig-6 gene was associated with smoking patients, squamous cell carcinoma patients and late-stage patients. Furthermore, 3 markers, D2S2968, D6S2439 and D7S1818, were significantly associated with poor prognosis of NSCLC patients using both univariate and multivariate Cox's regression analyses (p = 0.035, 0.022 and 0.006, respectively). These markers can potentially be used for early lung cancer detection, outcome measurement and the positional cloning of new TSGs whose loss of function contributes to NSCLC tumorigenesis.

Aged↗

Etiology of community acquired pneumonia among adult patients requiring hospitalization in Taiwan.

BACKGROUND: There has not been a comprehensive multi-center study investigating the microbial profile of community acquired pneumonia (CAP) in Taiwan. METHODS: A prospective study of adult CAP patients requiring hospitalization between December 2001 and April 2002 was carried out in 13 hospitals in Taiwan. Etiology was determined based on laboratory data from blood and sputum cultures plus serology from paired serum and urine antigen detection tests. RESULTS: Etiology was assigned to 99 (58.9%) of the 168 patients having the most complete data for etiology determination, with mixed infection in 21 (12.5%) patients. More than half (51.8%) of the patients were>60 years and 63.7% of the patients were males. The most common etiologic agent was Streptococcus pneumoniae (40, 23.8%), the majority (60%, 24 cases) of which was detected by positive urine antigen test. Other common agents included Mycoplasma pneumoniae (24, 14.3%), Chlamydia pneumoniae (12, 7.1%), Influenza A virus (11, 6.5%), Klebsiella pneumoniae (8, 4.8%) and Haemophilus influenzae (8, 4.8%). The prevalence of S. pneumoniae and M. pneumoniae was highest in patients>60 years (25/87, 28.7%), and<44 years (12/59, 19%), respectively; while K. pneumoniae comprised a larger proportion (4/22, 18%) in the 45-59 years group. CONCLUSIONS: S. pneumoniae was the most common etiology agent in adult patients hospitalized due to CAP in Taiwan and the spectrum of other major pathogens was similar to studies conducted elsewhere in the world. Empiric treatment recommendations developed in other parts of the world may be appropriately adapted for local use after taking into account local resistance profiles. Our data also support the recommendation that urine antigen test be added as an adjunct to adult CAP etiology diagnosis protocol.

Adolescent↗

Invasive amebiasis as an emerging parasitic disease in patients with human immunodeficiency virus type 1 infection in Taiwan.

BACKGROUND: Whether risk of invasive amebiasis due to Entamoeba histolytica is higher among human immunodeficiency virus (HIV)-infected persons than uninfected persons remains unclear, although intestinal colonization by Entamoeba dispar is common among men who have sex with men. Our objective was to determine the prevalence of invasive amebiasis and intestinal colonization by E histolytica and E dispar in HIV-infected persons and uninfected controls. METHODS: We assessed the prevalence of invasive amebiasis by case review of 951 HIV-infected persons and by serologic studies of 634 of the 951 HIV-infected persons, 429 uninfected controls with gastrointestinal symptoms, and 178 uninfected healthy controls using indirect hemagglutination antibody assay. We assessed the rate of intestinal colonization by E histolytica and E dispar by fecal antigen and polymerase chain reaction tests in 332 asymptomatic HIV-infected persons and 144 of the 178 uninfected healthy controls. RESULTS: Forty-nine (5.2%) of 951 HIV-infected persons had 51 episodes of invasive amebiasis. A high indirect hemagglutination antibody titer was detected in 39 (6.2%) of 634 HIV-infected persons compared with 10 (2.3%) of 429 uninfected controls with gastrointestinal symptoms and 0 of 178 uninfected healthy controls (P<.001). Stool specimens from 40 (12.1%) of 332 HIV-infected persons and 2 (1.4%) of 144 uninfected healthy controls were positive for E histolytica or E dispar antigen (P<.001). Ten (25.0%) of the 40 antigen-positive stool specimens from HIV-infected persons contained E histolytica. CONCLUSION: Persons infected with HIV in Taiwan are at increased risk for invasive amebiasis and exhibit a relatively high frequency of elevated antibody titers and intestinal colonization with E histolytica.

AIDS-Related Opportunistic Infections↗

A two-stage design for bridging studies.

The 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 based on its proven efficacy and safety. One of the current issues for evaluation of bridging studies is a cross-study comparison. Therefore, bias occurs when the study is not internally valid. A two-stage approach is proposed to overcome the issue of internal validity and at the same time to meet the objective of minimizing unnecessary duplication of clinical data required by the ICH E5 guideline. Under the framework of the proposed two-stage design, the bridging study of the new region is a second-stage substudy of the whole trial, and the patients for the bridging substudy are enrolled only after the data obtained in the original region demonstrate a statistically significantly positive treatment effect. Methods for the determination of the sample size for each region and the critical values at each stage are also proposed.

Clinical Trials as Topic↗

Evaluation of experimental designs for two-color cDNA microarrays.

The major goal of two-color cDNA microarray experiments is to measure the relative gene expression level (i.e., relative amount of mRNA) of each gene between samples in studies of gene expression. More specifically, given an N-sample experiment, we need all N(N - 1)/2 relative expression levels of all sample pairs of each gene for identification of the differentially expressed genes and for clustering of gene expression patterns. However, the intensities observed from two-color cDNA microarray experiments do not simply represent the relative gene expression level. They are composed of signal (gene expression level), noise, and other factors. In discussions on the experimental design of two-color cDNA microarray experiments, little attention has been given to the fact that different combinations of test and control samples will produce microarray intensities data with varying intrinsic composition of factors. As a consequence, not all experimental designs for two-color cDNA microarray experiments are able to provide all possible relative gene expression levels. This phenomenon has never been addressed. To obtain all possible relative gene expression levels, a novel method for two-color cDNA microarray experimental design evaluation is necessary that will allow the making of an accurate choice. In this study, we propose a model-based approach to illustrate how the factor composition of microarray intensities changed with different experimental designs in two-color cDNA microarray experiments. By analyzing 12 experimental designs (including 5 general forms), we demonstrate that not all experimental designs are able to provide all possible relative gene expression levels due to the differences in factor composition. Our results indicate that whether an experimental design can provide all possible relative expression levels of all sample pairs for each gene should be the first criterion to be considered in an evaluation of experimental designs for two-color cDNA microarray experiments.

Animals↗

Colonization of human immunodeficiency virus-infected outpatients in Taiwan with Candida species.

To understand the Candida colonization of human immunodeficiency virus (HIV)-infected outpatients in Taiwan, we have conducted a prospective cohort study of Candida colonization and its risk factors at the National Taiwan University Hospital from 1999 to 2002. More than 50% of the patients were colonized with Candida species, and 12% developed symptomatic candidiasis. Patients colonized with fluconazole-resistant strains of Candida species had a higher prevalence of candidiasis than those colonized with susceptible strains. Our analysis found that antibiotic treatment and lower CD4(+) counts (<200 cells/mm(3)) increased the rate of oropharyngeal candidiasis in HIV-infected patients, while antiretroviral therapy protected patients from the development of candidiasis.

AIDS-Related Opportunistic Infections↗

Herpes zoster in HIV-1-infected patients in the era of highly active antiretroviral therapy: a prospective observational study.

Between June 1994 and May 2003, 93 of 716 (13.0%) HIV-infected patients with a median baseline cell differentiation CD4+ count of 61 x 10(6) cells/L (range, 1-1206 x 10(6) cells/L) developed 103 episodes of herpes zoster [HZ], with an incidence of 5.67 per 100 person-years (PY). The incidence of HZ in the pre-highly active antiretroviral therapy (HAART) era (17.21 per 100 PY) was significantly higher than that in the post-HAART era (5.05 per 100 PY) (P < 0.0001). In the first six months of enrollment, the incidence of HZ was significantly higher than that between six and 12 months both in the pre-HAART (27.65 per 100 PY versus 8.43 per 100 PY, P = 0.02) and post-HAART era (17.79 per 100 PY versus 3.39 per 100 PY, P < 0.0001). In multivariate analyses, only baseline CD4+ count remained a significant risk factor associated with HZ. HZ did not increase mortality rate either in the pre-HAART or post-HAART era, although the risk for HIV progression was significantly higher in patients with HZ (adjusted odds ratio [OR], 1.747, 95% confidence interval, 1.037-2.943). We conclude that the incidence of HZ was highest in the first six months of enrollment in patients at late stage of HIV infection, which did not increase with the introduction of HAART. Baseline CD4+ lymphocyte count was the most significant risk factor associated with development of HZ. HZ was associated with increased risk for HIV progression, but not mortality.

AIDS-Related Opportunistic Infections↗

An autosomal genome-wide scan for loci linked to pre-diabetic phenotypes in nondiabetic Chinese subjects from the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance Family Study.

Type 2 diabetes is a complex disease involving both genetic and environmental components. Abnormalities in insulin secretion and insulin action usually precede the development of type 2 diabetes and can serve as good quantitative measures for genetic mapping. We therefore undertook an autosomal genomic search to locate the quantitative trait locus (QTL) linked to these traits in 1,365 nondiabetic Chinese subjects from 411 nuclear families. Residuals of these log-transformed quantitative traits were analyzed in multipoint linkage analysis using a variance-components approach. The most significant QTL for fasting insulin, which coincides with the QTL for homeostasis model assessment of insulin resistance, was located at 37 cM on chromosome 20, with a maximum empirical logarithm of odds (LOD) score of 3.01 (empirical P = 0.00006) when adjusted for age, sex, BMI, antihypertensive medications, recruitment centers, and environmental factors. In the same region, a QTL for fasting glucose was identified at 51 cM, with an empirical LOD score of 2.03 (empirical P = 0.0012). There were other loci with maximum empirical LOD scores >or=1.29 located on chromosomes 1q, 2p, 5q, 7p, 9q, 10p, 14q, 18q, and 19q for different diabetes-related traits. These loci may harbor genes that regulate glucose homeostasis either independently or via interactions of the genes within these regions.

Asian People↗

Clinical experience of the 23-valent capsular polysaccharide pneumococcal vaccination in HIV-1-infected patients receiving highly active antiretroviral therapy: a prospective observational study.

To assess the impact of vaccination with 23-valent pneumococcal polysaccharide vaccine on the risks for development of pneumococcal disease, all-cause community-acquired pneumonia, HIV progression, and mortality and immunologic and virologic responses among HIV-1-infected patients treated with highly active antiretroviral therapy (HAART), we conducted a 2-year prospective observational cohort study at a university hospital in Taiwan. A total of 305 HIV-1-infected patients who received 23-valent pneumococcal vaccine (vaccinees) and 203 patients who did not (non-vaccinees) were prospectively observed between 1 June 2000 and 31 October 2002. Changes of CD4+ and plasma viral load (PVL) from baseline to week 4 of vaccination were assessed in 31 randomly selected vaccinees. The incidence of pneumococcal disease and bacteremia of vaccinees was 2.1 per 1000 patient-years (PY) (95% confidence interval (95% CI), 1.7-2.5 per 1000 PY) over the median observation of 641 days (range, 37-832 days) following vaccination while that of non-vaccinee was 21.8 per 1000 PY (95% CI, 20.1-23.7 per 1000 PY) and 7.3 per 1000 PY (95% CI, 7.0-7.6 per 1000 PY), respectively, over the observation of 500 days (range, 32-851 days), with an adjusted odds ratio (AOR) for developing pneumococcal disease of 0.085 (95% CI, 0.010-0.735) and for bacteremia of 0.22 (95% CI, 0.018-2.561). The median CD4+ count increased by 45 x 10(6) l(-1) (P = 0.01) and median PVL change was 0 log(10) copies/ml (range of decrease, -0.74 to 2.47 log(10) copies/ml) after 1 month of pneumococcal vaccination among the subgroup of 31 vaccinees receiving HAART. The median CD4+ count increase from baseline to the end of study was 149 x 10(6) l(-1) for vaccinees and 107 x 10(6) l(-1) for non-vaccinees (P = 0.21). The AOR of developing all-cause community-acquired pneumonia and new AIDS-defining opportunistic illnesses (OI) of vaccinees as compared to non-vaccinees was 1.876 (95% CI, 0.785-4.485) and 0.567 (95% CI, 0.217-1.484), respectively. Death rate of vaccinees and non-vaccinees was 17.7 per 1000 PY (95% CI, 16.5-18.9 per 1000 PY) and 80.5 per 1000 PY (95% CI, 77.1-83.9 per 1000 PY), respectively. Adjusted hazard ratio for death of vaccinees as compared with non-vaccinees was 0.733 (95% CI, 0.236-2.274). Our data suggested that vaccination with 23-valent pneumococcal polysaccharide vaccine and receipt of HAART were associated with reduced risks for pneumococcal disease among HIV-1-infected patients receiving HAART. Vaccination did not increase the risks of all-cause community-acquired pneumonia, HIV progression, and mortality. Vaccination did not increase PVL or decrease CD4+ among HIV-1-infected patients receiving HAART.

Adult↗

Clustering of minimal deleted regions reveals distinct genetic pathways of human hepatocellular carcinoma.

Systematic scan and statistical analysis of loss of heterozygosity (LOH) has been widely used to define chromosomal aberrations in various cancers for cloning of tumor suppressor genes and for development of prognostic markers. However, the establishment of novel strategies is needed, so that the nonrandom but heterogeneous chromosomal aberration data could provide significant insights into our understanding of molecular pathogenesis of cancers. After comprehensive allelotyping of recurrent allelic losses with 441 highly informative microsatellite markers and overlapping LOH regions on human hepatocellular carcinoma (HCC) chromosomes, 33 minimal deleted regions (MDRs) were revealed. Five and 15 of the 33 MDRs have physical intervals in less than 5 and 10 Mb, respectively, with the smallest MDR9p1 of 2.2 Mb located at 9p21.3-p21.2. Statistical and Kaplan-Meier survival analysis revealed a significant association between the loss of MDR15q1 (15q21.1-q22.2) and the HCC patient survival (adjusted P = 0.033). After cluster analysis of 33 MDRs that represented LOH profiles of each HCC tissue based on clinicopathological features and p53 mutations, two major genetic pathways, low-stage and advanced-stage HCC, were uncovered based on high concordance of MDR clusters. We propose that the definition of genome-wide MDRs on the cancer genome not only narrows down the location of existing tumor suppressor genes to facilitate positional candidate cloning and develop potential prognostic markers after statistical association of MDRs with clinicopathological features but also dissects genetic interactions and pathways of chromosomal aberrations in tumorigenesis.

Carcinoma, Hepatocellular↗

Impact of chronic hepatitis B virus (HBV) infection on outcomes of patients infected with HIV in an area where HBV infection is hyperendemic.

Between June 1994 and February 2003, a total of 111 human immunodeficiency virus (HIV)-infected patients with chronic hepatitis B virus (HBV) coinfection and 387 HIV-infected patients without HBV or hepatitis C virus coinfection were prospectively observed to assess the impact of HBV infection on outcomes of HIV-infected patients. After a median duration of observation of 25 months, coinfected patients were more likely to develop hepatitis (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [CI], 1.69-3.82) and hepatic decompensation (adjusted odds ratio [AOR], 9.94; 95% CI, 1.89-52.35). Although similar proportions of the 2 patient groups had an increase in the CD4 count by > or =100x10(6) cells/L (AOR, 0.78; 95% CI, 0.45-1.36) and development of new opportunistic illnesses (AOR, 0.94; 95% CI, 0.53-1.66), HBV-infected patients had an increased risk for virologic failure (AOR, 1.76; 95% CI, 1.03-2.99) and death (AHR, 1.71; 95% CI, 1.19-2.47) after highly active antiretroviral therapy was initiated.

Adolescent↗

The insulin sensitivity, glucose effectiveness and acute insulin response to glucose load of non-obese adolescent type 2 diabetes.

To determine the clinical characteristics in adolescent type 2 diabetes (young diabetes, YDM) in Taiwan, we enrolled 11 males who were diagnosed with YDM before 19 years of age into our study. Another 11 patients with adult type 2 diabetes (mature age diabetes, MADM) who were diagnosed after the age of 40 were enrolled as compare group. Subjects from both groups were being treated with oral hypoglycemic agents only at the time of enrollment, and none of the subjects had a history of diabetic ketoacidosis. Plasma lipid levels were measured from the fasting plasma sample. A homeostasis model assessment was used to estimate insulin sensitivity (HOMA-S) and beta-cell function (HOMA-B). Frequent-sampled intravenous glucose tolerance test was also performed to measure the insulin sensitivity (S(I)), glucose effectiveness (E(G)), and acute insulin response after glucose load (AIR). After adjusting for age and BMI, fasting plasma glucose, total cholesterol, HDL-cholesterol, triglycerides, and HOMA-B levels were similar between two groups. The fasting plasma insulin and HOMA-S were significantly higher in YDM. However, the S(I), E(G) and AIR in both groups were also not significantly different. In conclusion, the early onset of diabetes in YDM may be due to the early deterioration of the S(I), E(G) and AIR with similar severity compared with MADM. The role of E(G) might be more important than previously thought in these patients. Finally, the YDM might be a subtype of type 2 diabetes.

Adolescent↗