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author:("greater, Alan")
1.  Acute Respiratory Failure and Active Bleeding Are the Important Fatality Predictive Factors for Severe Dengue Viral Infection 
PLoS ONE  2014;9(12):e114499.
To determine the outcome of severe dengue viral infection (DVI) and the main dengue fatality risk factors.
Study design
The medical records of patients aged <15 years admitted to Songklanagarind Hospital in southern Thailand during 1989–2011 were reviewed. Patients who had dengue hemorrhagic fever (DHF) grades III–IV, organ failure (cardiovascular, respiratory, liver, renal or hematologic), impaired consciousness, or aspartate aminotransferase more than 1,000 units/L, were classified as having severe DVI. To determine the fatality risk factors of severe DVI, the classification trees were constructed based on manual recursive partitioning.
Of the 238 children with severe DVI, 30 (12.6%) died. Compared to the non-fatal DVI cases, the fatal cases had higher rates of DHF grade IV (96.7% vs 24.5%), repeated shock (93.3% vs 27.9%), acute respiratory failure (ARF) (100% vs 6.7%), acute liver failure (ALF) (96.6% vs 6.3%), acute kidney injury (AKI) (79.3% vs 4.5%), and active bleeding requiring blood transfusion (93.3% vs 5.4%), all p<0.01. The combined risk factors of ARF and active bleeding considered together predicted fatal outcome with sensitivity, specificity, and negative and positive predictive values of 0.93 (0.78–0.99), 0.97 (0.93–0.99), 0.99 (0.97–1.00), and 0.82 (0.65–0.93), respectively. The likelihood ratios for a fatal outcome in the patients who had and did not have this risk combination were 32.4 (14.6–71.7) and 0.07 (0.02–0.26), respectively.
Severe DVI patients who have ARF and active bleeding are at a high risk of death, while patients without these things together should survive.
PMCID: PMC4252142  PMID: 25460594
2.  Elevated Lead Contamination in Boat-caulkers’ Homes in Southern Thailand 
Surface-wipe lead loading was measured at various locations in the homes of 31 boat-caulkers and 31 location-matched controls to identify factors associated with household lead contamination. Data were obtained by observation checklist and questionnaire. Lead loading was significantly higher in caulkers’ than in control households. Median lead loadings (in µg/ft2) of various locations in caulkers’ homes were windowsill, 43.9; exterior entrance, 9.5; interior entrance, 21.1; living room floor, 9.8; and bedroom floors 15.6. Corresponding levels in control homes were all less than 0.2 µg/ft2. Regression modeling indicated that lead loading was higher in caulkers’ homes that were closer to a boatyard, in which the caulker had a longer duration of boatyard work, and in which there were no children aged under 6 years resident. Exterior and interior entrance and living room floors had lower lead loading than windowsills. However, bedroom floors had significantly higher lead loading, similar to windowsills.
PMCID: PMC4040288  PMID: 19650583
boat-caulkers; lead exposure; take-home lead; surface lead contamination; lead loading
3.  Comparison of intelligence, weight and height in children after general anesthesia with and without perioperative desaturation in non-cardiac surgery: a historical and concurrent follow-up study 
SpringerPlus  2014;3:164.
To determine whether perioperative desaturation (PD) in preschool children undergoing non-cardiac surgery is associated with subsequent impairment of intelligence or subsequent change in age-specific weight and height percentile.
A historical-concurrent follow-up study was conducted in children aged ≤ 60 months who underwent general anesthesia (GA) for non-cardiac surgery between January 2008 and December 2011 at Songklanagarind Hospital. Children who developed PD (PD group) and children who did not develop perioperative respiratory events (no-PRE group) were matched on sex, age, year of having index GA, type of surgery and choice of anesthesia. The children’s age-specific weight and height percentile and intelligence quotient (IQ) scores by Standford Binet-LM or Wechsler Intelligence Scale for Children, 3rd edition 12–60 months after GA were compared using Student’s t- test and Wilcoxon’s rank sum test. Multivariate linear regression models for standardized IQ and multivariate mixed effects linear regression models for the change of age-specific weight and height percentile from the time of index GA to the time of IQ test were performed to identify independent predictors. The coefficients and 95% confidence intervals (CI) were displayed and considered significant if the F test p-values were < 0.05.
Of 103 subjects in each group (PD vs no-PRE), there were no statistically significant differences in IQ (94.7 vs 98.3, p = 0.13), standardized IQ (−0.1 vs 0.1, p = 0.14) or age-specific weight percentile (38th vs 63th, p = 0.06). However, age-specific height percentile in the PD group at the time of IQ test was significantly lower (38th vs 50th, p = 0.02). In the multivariate analysis, PD was not a significant predictor for standardized IQ (coefficient: −0.06, 95% CI: −0.3, 0.19, p = 0.57), change in age-specific weight percentile (coefficient: 4.66, 95% CI: −2.63, 11.95, p = 0.21) or change in age-specific height percentile (coefficient: −1.65, 95% CI: −9.74, 6.44, p = 0.69) from the time of index GA to the time of IQ test after adjusting for family and anesthesia characteristics.
Our study could not demonstrate any serious effect of PD on subsequent intelligence or on the change in age-specific weight and height percentile of children after non-cardiac surgery.
Electronic supplementary material
The online version of this article (doi:10.1186/2193-1801-3-164) contains supplementary material, which is available to authorized users.
PMCID: PMC4320222
Perioperative desaturation; Weight; Height; Intelligence; Pediatric anesthesia; Non-cardiac surgery
4.  Risk over time and risk factors of intraoperative respiratory events: a historical cohort study of 14,153 children 
BMC Anesthesiology  2014;14:13.
The variation in the rate of intraoperative respiratory events (IRE) over time under anesthesia and the influence of anesthesia-related factors have not yet been described. The objectives of this study were to describe the risk over time and the risk factors for IRE in children at a tertiary care hospital in southern Thailand.
The surveillance anesthetic database and chart review of IRE of 14,153 children who received surgery at Songklanagarind Hospital during January 2005 to December 2011 were used to obtain demographic, surgical and anesthesia-related data. Incidence density of IRE per person-time was determined by a Poisson modelling. Risk of IRE over time was displayed using Kaplan Meier survival and Nelson-Aalen curves. Multivariate Cox regression was employed to identify independent predictors for IRE. Adjusted hazard ratios (HR) and their 95% confidence intervals (CI) were obtained from the final Cox model.
Overall, IRE occurred in 315 out of 14,153 children. The number (%) of desaturation, wheezing or bronchospasm, laryngospasm, reintubation and upper airway obstruction were 235 (54%), 101 (23%), 75 (17%), 21 (5%) and 4 (1%) out of 315 IRE, respectively. The incidence density per 100,000 person-minutes of IRE at the induction period (61.3) was higher than that in the maintenance (13.7) and emergence periods (16.5) (p < 0.001). The risk of desaturation, wheezing and laryngospasm was highest during the first 15, 20 and 30 minutes of anesthesia, respectively. After adjusting for age, history of respiratory disease and American Society of Anesthesiologist (ASA) classification, anesthesia-related risk factors for laryngospasm were assisted ventilation via facemask (HR: 18.1, 95% CI: 6.4-51.4) or laryngeal mask airway (HR: 12.5, 95% CI: 4.6-33.9) compared to controlled ventilation via endotracheal tube (p < 0.001), and desflurane (HR: 11.0, 95% CI: 5.1-23.9) compared to sevoflurane anesthesia (p < 0.001).
IRE risk was highest in the induction and early maintenance period. Assisted ventilation via facemask or LMA and desflurane anesthesia were anesthesia-related risk factors for laryngospasm. Therefore, anesthesiologists should pay more attention during the induction and early maintenance period especially when certain airway devices incorporated with assisted ventilation or desflurane are used.
PMCID: PMC4016417  PMID: 24597484
Risk over time; Intraoperative period; Respiratory events; Pediatric anesthesia; Tertiary care hospital
5.  Migrant workers’ occupation and healthcare-seeking preferences for TB-suspicious symptoms and other health problems: a survey among immigrant workers in Songkhla province, southern Thailand 
Much of the unskilled and semi-skilled workforce in Thailand comprises migrant workers from neighbouring countries. While, in principle, healthcare facilities in the host country are open to those migrants registered with the Ministry of Labour, their actual healthcare-seeking preferences and practices, as well as those of unregistered migrants, are not well documented. This study aimed to describe the patterns of healthcare-seeking behaviours of immigrant workers in Thailand, emphasizing healthcare practices for TB-suspicious symptoms, and to identify the role of occupation and other factors influencing these behaviours.
A survey was conducted among 614 immigrant factory workers (FW), rubber tappers (RT) and construction workers (CW), in which information was sought on socio-demography, history of illness and related healthcare-seeking behaviour. Mixed effects logistic regression modeling was employed in data analysis.
Among all three occupations, self-medication was the most common way of dealing with illnesses, including the development of TB-suspicious symptoms, for which inappropriate drugs were used. Only for GI symptoms and obstetric problems did migrant workers commonly seek healthcare at modern healthcare facilities. For GI illness, FW preferred to attend the in-factory clinic and RT a private facility over government facilities owing to the quicker service and greater convenience. For RT, who were generally wealthier, the higher cost of private treatment was not a deterrent. CW preferentially chose a government healthcare facility for their GI problems. For obstetric problems, including delivery, government facilities were utilized by RT and CW, but most FW returned to their home country. After adjusting for confounding, having legal status in the country was associated with overall greater use of government facilities and being female and being married with use of both types of modern healthcare facility. One-year estimated period prevalence of TB-suspicious symptoms was around 6% among FW but around 27% and 30% in RT and CW respectively. However, CW were the least likely to visit a modern healthcare facility for these symptoms.
Self medication is the predominant mode of healthcare seeking among these migrant workers. When accessing a modern healthcare facility the choice is influenced by occupation and its attendant lifestyle and socioeconomic conditions. Utilization of modern facilities could be improved by reducing the current barriers by more complete registration coverage and better provision of healthcare information, in which local vendors of the same ethnicity could play a useful role. Active surveillance for TB among migrant workers, especially CW, may lead to better TB control.
PMCID: PMC3478184  PMID: 23031509
6.  Use of traditional cooking fuels and the risk of young adult cataract in rural Bangladesh: a hospital-based case-control study 
BMC Ophthalmology  2011;11:16.
This study aimed to investigate the independent relationship between the use of various traditional biomass cooking fuels and the occurrence of cataract in young adults in rural Bangladesh.
A hospital-based age- and sex-matched case-control study incorporating two control groups was conducted. Cases were cataract patients aged 18 and 49 years diagnosed on the basis of any opacity of the crystalline lens or its capsule and visual acuity poorer than 6/18 on the Log Mar Visual Acuity Chart in either eye, or who had a pseudophakic lens as a result of cataract surgery within the previous 5 years. Non-eye-disease (NE) controls were selected from patients from ENT or Orthopaedics departments and non-cataract eye-disease (NC) controls from the Ophthalmology department. Data pertaining to history of exposure to various cooking fuels and to established risk factors for cataract were obtained by face-to-face interview and analyzed using conditional logistic regression.
Clean fuels were used by only 4% of subjects. A majority of males (64-80% depending on group) had never cooked, while the rest had used biomass cooking fuels, mainly wood/dry leaves, with only 6 having used rice straw and/or cow dung. All females of each group had used wood/dry leaves for cooking. Close to half had also used rice straw and/or cow dung. Among females, after controlling for family history of cataract and education and combining the two control groups, case status was shown to be significantly related to lifetime exposure to rice straw, fitted as a trend variable coded as never, ≤ median of all exposed, > median of all exposed (OR = 1.52, 95%CI 1.04-2.22), but not to lifetime exposure to wood/dry leaves. Case status among females showed an inverse association with ever use of cow dung as a cooking fuel (OR 0.43, 95%CI 0.22-0.81).
In this population, where cooking is almost exclusively done using biomass fuels, cases of young adult cataract among females were more likely to have had an increased lifetime exposure to cooking with rice straw fuel and not to have cooked using cow dung fuel. There is a possibility that these apparent associations could have been the result of uncontrolled founding, for instance by wealth. The nature of the associations, therefore, needs to be further investigated.
PMCID: PMC3148558  PMID: 21679452
Young adult cataract; risk factor; traditional cooking fuels; Bangladesh
8.  Effect of household and village characteristics on financial catastrophe and impoverishment due to health care spending in Western and Central Rural China: A multilevel analysis 
The study aimed to examine the effect of household and community characteristics on financial catastrophe and impoverishment due to health payment in Western and Central Rural China.
A household survey was conducted in 2008 in Hebei and Shaanxi provinces and the Inner Mongolia Autonomous Region using a multi-stage sampling technique. Independent variables included village characteristics, household income, chronic illness status, health care use and health spending. A composite contextual variable, named village deprivation, was derived from socio-economic status and availability of health care facilities in each village using factor analysis. Dependent variables were whether household health payment was more than 40% of household's capacity to pay (catastrophic health payment) and whether household per capita income was put under Chinese national poverty line (1067 Yuan income per year) after health spending (impoverishment). Mixed effects logistic regression was used to assess the effect of the independent variables on the two outcomes.
Households with low per capita income, having elderly, hospitalized or chronically ill members, and whose head was unemployed were more likely to incur financial catastrophe and impoverishment due to health expenditure. Both catastrophic and impoverishing health payments increased with increased village deprivation. However, the presence of a village health clinic had no effect on the two outcomes, nor did household enrollment in the New Rural Cooperative Medical Scheme (national health insurance).
Village deprivation independently increases the risk for financial hardship due to health payment after adjusting for known household-level factors. This suggests that policy makers need to view the individual, household and village as separate units for policy targeting.
PMCID: PMC3080794  PMID: 21466714
9.  Predictors for Abundance of Host Flea and Floor Flea in Households of Villages with Endemic Commensal Rodent Plague, Yunnan Province, China 
From 1990 to 2006, fifty-five natural villages experienced at least one plague epidemic in Lianghe County, Yunnan Province, China. This study is aimed to document flea abundance and identify predictors in households of villages with endemic commensal rodent plague in Lianghe County.
Trappings were used to collect fleas and interviews were conducted to gather demography, environmental factors, and other relevant information. Multivariate hurdle negative binomial model was applied to identify predictors for flea abundance.
A total of 344 fleas were collected on 101 small mammals (94 Rattus flavipectus and 7 Suncus murinus). R. flavipectus had higher flea prevalence and abundance than S. murinus, but the flea intensities did not differ significantly. A total of 315 floor fleas were captured in 104 households. Xenopsylla cheopis and Ctenocephalides felis felis were the predominant flea species on the host and the floor flea, respectively. The presence of small mammal faeces and R. flavipectus increased host flea prevalence odds 2.9- and 10-fold, respectively. Keeping a dog in the house increased floor flea prevalence odds 2-fold. Keeping cattle increased floor flea intensity by 153%. Villages with over 80% of houses raising chickens had increased prevalence odds and intensity of floor flea about 2.9- and 11.6-fold, respectively. The prevalence and intensity of floor flea in brick and wood houses were decreased by 60% and 90%, respectively. Flea prevalences of host and floor flea in the households that were adjacent to other houses were increased 7.4- and 2.2-fold, respectively. Houses with a paddy nearby decreased host flea intensity by 53%, while houses with an outside toilet increased host flea intensity by 125%.
Rodent control alone may not be sufficient to control plague risk in these areas. In order to have successful results, plague control programs should pay attention to ecological and hygiene factors that influence flea populations.
Author Summary
Yunnan province is located in southwest China. Plague is still a huge threat to the health of local people in Yunnan where plague epidemics had the most serious impacts than other provinces in China. The risk of plague outbreak is driven by rodent and flea populations. Our research team is conducting a study to identify predictors for abundance of host and floor fleas in households of villages with endemic commensal rodent plague in Yunnan province. The results of this study will contribute to control host and floor flea populations, and therefore to prevent and control plague outbreaks in these areas.
PMCID: PMC3066137  PMID: 21468306
10.  The influence of the rural health security schemes on health utilization and household impoverishment in rural China: data from a household survey of western and central China 
The New Rural Cooperative Medical Scheme (NRCMS, voluntary health insurance) and the Medical Financial Assistance (MFA, financial relief program) were established in 2003 for rural China. The aim of this study was to document their coverage, assess their effectiveness on access to in-patient care and protection against financial catastrophe and household impoverishment due to health spending, and identify the factors predicting impoverishment with and without these schemes.
A cross-sectional household survey was conducted in 2008 in Hebei and Shaanxi provinces and the Inner Mongolia Autonomous Region using a multi-stage sampling technique. Information on personal demographic characteristics, chronic illness status, health care use, household expenditure, and household health spending were collected by interview.
NRCMS covered 90.8% of the studied individuals and among the designated poor, 7.6% had their premiums paid by MFA. Of those referred for hospitalization in the year prior to the interview, 34.3% failed to comply, mostly (80.2%) owing to financial constraints. There was no significant difference in the unmet need for admission between the insured with NRCMS and the uninsured. Before reimbursement, the incidence of catastrophic health payment (household health spending more than 40% of household's capacity to pay) and medical impoverishment (household per capita income falling below the poverty line due to medical expense) was 14.3% and 8.2%, respectively. NRCMS prevented 9.9% of the households from financial catastrophe and 7.7% from impoverishment, whereas MFA kept just one household from impoverishment and had no effect on financial catastrophe. Household per capita expenditure and household chronic disease proportion (proportion of members of a household with chronic illness) were the most important determinants of the unmet need for admission, risk of being impoverished and the chance of not being saved from impoverishment.
The coverage of NRCMS among the rural population was high but not adequate to improve access to in-patient care and protect against financial catastrophe and household impoverishment due to health payment, especially for the poor and the chronically ill. Furthermore, MFA played almost no such role; therefore, the current schemes need to be improved.
PMCID: PMC2838900  PMID: 20178565
11.  Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load 
AIM: To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus (HBV) replication in different clinical stages of chronic HBV infection.
METHODS: A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages: immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. Serum HBV DNA load was assessed by quantitative real-time polymerase chain reaction.
RESULTS: CD8+ T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages (36.87 ± 7.58 vs 34.37 ± 9.07, 36.87 ± 7.58 vs 28.09 ± 5.64, P < 0.001). The peripheral blood in patients at the immune-tolerant and immune active stages contained more CD8+ T-cells than CD4+ T-cells (36.87 ± 7.58 vs 30.23 ± 6.35, 34.37 ± 9.07 vs 30.92 ± 7.40, P < 0.01), whereas the peripheral blood in patients at the immune-inactive carrier stage and in normal controls contained less CD8+ T-cells than CD4+ T-cells (28.09 ± 5.64 vs 36.85 ± 6.06, 24.02 ± 4.35 vs 38.94 ± 3.39, P < 0.01). ANOVA linear trend test showed that CD8+ T-cells were significantly increased in patients with a high viral load (39.41 ± 7.36, 33.83 ± 7.50, 31.81 ± 5.95 and 26.89 ± 5.71, P < 0.001), while CD4+ T-cells were significantly increased in patients with a low HBV DNA load (37.45 ± 6.14, 33.33 ± 5.61, 31.58 ± 6.99 and 27.56 ± 5.49, P < 0.001). Multiple regression analysis displayed that log copies of HBV DNA still maintained its highly significant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3+, CD4+ and CD8+ cells and CD4+/CD8+ ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation.
CONCLUSION: Differences in peripheral T-cell subpopulation profiles can be found in different clinical stages of chronic HBV infection. T-cell impairment is significantly associated with HBV load.
PMCID: PMC2712899  PMID: 19610139
Hepatitis B virus; Chronic hepatitis B virus infection; Clinical stages; Hepatitis B virus DNA; T lymphocyte subpopulation
12.  Predictors for presence and abundance of small mammals in households of villages endemic for commensal rodent plague in Yunnan Province, China 
BMC Ecology  2008;8:18.
Ninety-one rodent plague epidemics have occurred in Lianghe county, Yunnan Province, China, between 1990 and 2006. This study aimed to identify predictors for the presence and abundance of small mammals in households of villages endemic for rodent plague in Lianghe county.
Rattus flavipectus and Suncus murinus were the two species captured in 110 households. Keeping cats decreased the number of captures of R. flavipectus by one to two thirds and the chance of reported small mammal sightings in houses by 60 to 80%. Food availability was associated with fewer captures. Keeping food in sacks decreased the small mammal captures, especially of S. murinus 4- to 8-fold. Vegetables grown around house and maize grown in the village reduced the captures of S. murinus and R. flavipectus by 73 and 45%, respectively. An outside toilet and garbage piles near the house each reduced R. flavipectus captures by 39 and 37%, respectively, while raising dogs and the presence of communal latrines in the village increased R. flavipectus captures by 76 and 110% but were without detectable effect on small mammal sightings. Location adjacent to other houses increased captures 2-fold but reduced the chance of sightings to about half. In addition, raising ducks increased the chance of sighting small mammals 2.7-fold. Even after adjusting for these variables, households of the Dai had higher captures than those of the Han and other ethnic groups.
Both species captures were reduced by availability of species-specific foods in the environment, whereas other predictors for capture of the two species differed. Other than the beneficial effect of cats, there were also discrepancies between the effects on small mammal captures and those on sightings. These differences should be considered during the implementation and interpretation of small mammal surveys.
PMCID: PMC2630958  PMID: 19068139
13.  Impact of viral replication inhibition by entecavir on peripheral T lymphocyte subpopulations in chronic hepatitis B patients 
To investigate dynamic fluctuations of serum viral load and peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their correlation during entecavir therapy.
Fifty-five patients received entecavir 0.5 mg/d therapy. Serum HBV DNA load was measured by Real-Time-PCR, and the levels of peripheral T-lymphocyte subpopulations by flow cytometry biweekly, every four weeks and every eight weeks during weeks 1–12, 13–24 and 24–48, respectively. Multilevel modelling was used to analyse the relationship between these variables.
Of the 55 patients, all HBeAg positive and with detectable HBV DNA, the majority (81.8%) had serum levels of HBV DNA over 107 copies per milliliter. HBV viral load dropped sharply during the first two weeks. In 28 and 43 patients, the level became undetectable from week 24 and 48, respectively. Using pre-therapy level as the reference, a significant decrease in CD8+ T cells and increase in CD4+ T cells were found from week 12. Both parameters and CD4+/CD8+ ratio steadily improved throughout the 48 weeks. Multilevel analyses showed that the level of decrement of HBV DNA was associated with the increment of T-lymphocyte activities only in the later period (4–48 week). After 4 weeks of therapy, for each log10 scale decrement of HBV DNA, the percentage of CD4+ lymphocyte was increased by 0.49 and that of CD8+ decreased by 0.51.
T-lymphocyte subpopulations could be restored partially by entecavir treatment in patients with chronic hepatitis B concurrently with reduction of viremia.
PMCID: PMC2570678  PMID: 18803883
14.  Hepatitis B virus DNA is more powerful than HBeAg in predicting peripheral T-lymphocyte subpopulations in chronic HBV-infected individuals with normal liver function tests 
AIM: To investigate the peripheral T-lymphocyte subpopulation profile, and its correlations with hepatitis B virus (HBV) replication level in chronic HBV-infected (CHI) individuals with normal liver function tests (LFTs).
METHODS: Frequencies of T-lymphocyte subpopu-lations in peripheral blood were measured by flow cytometry in 216 CHI individuals. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time PCR. Information of age at HBV infection, and maternal HBV infection status was collected. ANOVA linear trend test and linear regression were used in statistical analysis.
RESULTS: CHI individuals had significantly decreased relative frequencies of CD3+, CD4+ subpopulations and CD4+/CD8+ ratio, and increased CD8+ subset percentage compared with uninfected individuals (all P < 0.001). There was a significant linear relationship between the load of HBV DNA and the parameters of T-lymphocyte subpopulations (ANOVA linear trend test P < 0.01). The parameters were also significantly worse among individuals whose mothers were known to be HBV carriers, and those having gained infection before the age of 8 years. In multiple regressions, after adjustment for age at HBV infection and status of maternal HBV infection, log copies of HBV DNA maintained its highly significant predictive coefficient on T-lymphocyte subpopulations, whereas the effect of HBeAg was not significant.
CONCLUSION: HBV DNA correlates with modification in the relative T-lymphocyte subpopulation frequencies. High viral load is more powerful than HBeAg in predicting the impaired balance of T-cell subsets.
PMCID: PMC2719233  PMID: 18595137
Hepatitis B virus; Chronic hepatitis B virus infection; Hepatitis B virus DNA; T-lymphocyte subpopulation; Immune function
15.  Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B 
AIM: To investigate peripheral T-lymphocyte subpopulation profile and its correlation with hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB).
METHODS: Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction (PCR). The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed.
RESULTS: CHB patients had significantly decreased CD3+ and CD4+ cells and CD4+/CD8+ ratio, and increased CD8+ cells compared with uninfected controls (55.44 ± 12.39 vs 71.07 ± 4.76, 30.92 ± 7.48 vs 38.94 ± 3.39, 1.01 ± 0.49 vs 1.67 ± 0.33, and 34.39 ± 9.22 vs 24.02 ± 4.35; P < 0.001, respectively). Univariate analysis showed a similar pattern of these parameters was significantly associated with high viral load, presence of serum hepatitis B e antigen (HBeAg) expression, liver disease severity, history of maternal HBV infection, and young age at HBV infection, all with P < 0.01. There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations (linear trend test P < 0.001). There was a negative correlation between the levels of CD3+ and CD4+ cells and CD4+/CD8+ ratio and serum level of viral load in CHB patients (r = -0.68, -0.65 and -0.75, all P < 0.0001), and a positive correlation between CD8+ cells and viral load (r = 0.70, P < 0.0001). There was a significant decreasing trend in CD3+ and CD4+ cells and CD4+/CD8+ ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection (linear trend test P < 0.01). In multiple regression (after adjustment for age at HBV infection, maternal HBV infection status and hepatocyte damage severity) log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphocyte subpopulations, and was the strongest predictor of variation in CD3+, CD4+, CD8+ cells and CD4+/CD8+ ratio. However, the effect of HBeAg was not significant.
CONCLUSION: T-lymphocyte failure was significantly associated with viral replication level. The substantial linear dose-response relationship and strong independent predictive effect of viral load on T-lymphocyte subpopulations suggests the possibility of a causal relationship between them, and indicates the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients.
PMCID: PMC2689417  PMID: 18286696
Hepatitis B virus; Chronic hepatitis B virus infection; Hepatitis B virus DNA; T lymphocyte subpopulation; Immune function
16.  Contextual socioeconomic determinants of cardiovascular risk factors in rural south-west China: a multilevel analysis 
BMC Public Health  2007;7:72.
We examined independent influences of contextual variables on cardiovascular risk factors in Shilin county, Yunnan province, South-west China.
Three villages were selected from each of the ten townships based on probability proportional to size. In each selected village, 200 individuals aged ≥ 45 years were chosen based on simple random sampling method. From 6006 individuals, information on demographic characteristics, smoking and drinking status was obtained by interview. Blood pressure, height, weight, and waist and hip girth were measured. Fasting blood sugar was measured in a 10-percent subsample. Contextual data were from official reports. Multi-level regression modelling with adjustment for individual and contextual variables was used.
Contextual variables associated with CVD risk factors included: remoteness of village with higher blood pressure and fasting blood sugar, high proportion of Yi minority with drinking, high literacy rate with a lower rate of smoking and a lower mean waist-hip ratio, and high average income with lower systolic blood pressure and body mass index (BMI) but higher FBS.
While contextual SES is associated with a few CVD risk factors, villages with high level of income are worse off in fasting blood sugar. Strategies of economic development should be reviewed to avoid adverse effects on health.
PMCID: PMC1871581  PMID: 17480237
17.  Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B: A randomized controlled study 
AIM: To observe the efficiency and safety of thymosin-α1 treatment in patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis.
METHODS: Sixty-two patients were randomly divided into groups A and B. The patients in group A received subcutaneous injection of 1.6 mg thymosin-α1, twice a week (T-α1 group) for six months, and the patients in group B received 5 MU interferon alpha (IFN-α) each day for fifteen days, then three times weekly (IFN-α group) for six months. The results between two groups treated with and the group untreated with IFN-α which was followed up for 12 mo (historical control group consisting of 30 patients) were compared, and three groups were comparable between each other (P > 0.05) at baseline (age, sex, clinical history, biochemical, and serological parameters).
RESULTS: At the end of treatment, complete response, which was defined as alanine aminotransferase (ALT) normalization and HBV DNA and HBeAg loss, occurred in 9 of 29 (31.0%) patients in the T-α1 group and in 15 of 33 (45.5%) patients in the IFN-α group (χ2 = 1.36, P > 0.05). After a follow-up period of six months, a complete response was observed in 14 of 29 (48.3%) patients in the T-α1 group and in 9 of 33 (27.3%) patients in the IFN-α group (χ2 = 2.93, P > 0.05). Compared with the results observed in the historical control (HC) group untreated with IFN-α which was followed up for 12 mo, the rate of complete response was significantly higher in IFN-α group at the end of therapy (1 of 30 vs 15 of 33, χ2 = 14.72, P < 0.001) and in the T-α1 group at the end of follow-up (1 of 30 vs 14 of 29, χ2 = 15.71, P < 0.001). In T-α1 and IFN-α treatment groups, the area under (the plasma concentration time) curve (AUC) of negative HBV DNA and HBeAg was 34%, 17%, 31% and 19% smaller than that in the HC group. By the end of the follow-up period, the proportions of ALT normalization and negative HBV DNA in the T-α1 group were significantly higher than those in the IFN-α and HC groups. The odds of ALT normalization and negative HBV DNA at the end of the follow-up was three-fold higher in the T-α1 group than in the IFN-α group. Unlike IFN-α, T-α1 was well tolerated by all patients, and no side effects appeared in T-α1 group.
CONCLUSION: The results suggest that a 6-mo course of T-α1 therapy is effective and safe in patients with chronic hepatitis B. T-α1 is able to reduce HBV replication in patients with chronic hepatitis B. Furthermore, T-α1 is better tolerated than IFN-α and can gradually induce more sustained ALT normalization and HBV DNA and HBeAg loss. However, a response rate of 48.3% is still less ideal. A more effective therapeutic approach warrants further study.
PMCID: PMC4125683  PMID: 17075991
Chronic hepatitis B; Efficacy; Interferon-alpha; Thymosin alpha-1
18.  WT1 gene expression as a prognostic marker in advanced serous epithelial ovarian carcinoma: an immunohistochemical study 
BMC Cancer  2006;6:90.
WT1 is a tumor suppressor gene responsible for Wilms' tumor. WT1 reactivity is limited to ovarian serous carcinomas. Recent studies have shown that WT1 plays an important role in the progression of disease and indicates a poorer prognosis of human malignancies such as acute myeloid leukemia and breast cancer. The aims of this study were to determine the survival and recurrence-free survival of women with advanced serous epithelial ovarian carcinoma in relation to WT1 gene expression.
The study accrued women over an 18-year period, from 1987–2004. During the study period, 163 patients were diagnosed with advanced serous epithelial ovarian carcinoma and had undergone complete post-operative chemotherapy, but the final study group comprised 99 patients. The records of these women were reviewed and the paraffin-embedded tissue of these women stained with WT1 immunostaining. Survival analysis was performed using Kaplan-Meier and Cox regression methods.
Fifty patients showed WT1 staining and forty-nine did not. Five-year survival of non-staining and staining groups were 39.4% and 10.7% (p < 0.00005); five-year recurrence-free survival of these groups were 29.8% and ≤ 7.5% (p < 0.00005), respectively. For survival the HR of WT1 staining, adjusted for residual tumor and chemotherapy response, was 1.98 (95% CI 1.28–3.79), and for recurrence-free survival the HR was 3.36 (95% CI 1.60–7.03). The HR for recurrence-free survival was not confounded by any other variables.
This study suggests that expression of WT1 gene may be indicative of an unfavorable prognosis in patients with advanced serous epithelial ovarian carcinoma.
PMCID: PMC1479357  PMID: 16606472

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