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Biomedical subjects

T Li

Publications and source records attributed to T Li.

At least 19 recordsLinked to original sources

Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment.

OBJECTIVE: To examine the impact of added abatacept treatment on health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX). METHODS: The impact of abatacept treatment on HRQoL was examined in a longitudinal, randomised double blind, placebo controlled clinical trial. Effects of treatment on HRQoL were examined using repeated measures analysis of covariance and comparing rates of change in HRQoL across treatment groups. The relationship between American College of Rheumatology (ACR) clinical markers and disease duration with changes in HRQoL indicators was also examined. Finally, a responder analysis was used to examine the percentage of patients who improved by 0.5 SD in 12 months or who reached the normative levels seen in the US general population. RESULTS: Statistically significant improvements in the abatacept group relative to controls were observed across a range of HRQoL measures, including physical function, fatigue, all eight domains of the SF-36, and the physical and mental component summaries (PCS and MCS). Improvements were seen as early as day 29 for fatigue and for five out of eight SF-36 domains. By day 169, all HRQoL measures were significantly better with abatacept than with placebo. HRQoL gains were associated with greater ACR clinical improvement, and the effects were consistent for patients with different disease duration. A significantly greater percentage of patients treated with abatacept reached normative levels of PCS, MCS, physical functioning, and fatigue compared with patients treated with MTX alone. CONCLUSION: Combined abatacept and MTX treatment produces significant improvements across a wide range of HRQoL domains in patients with RA.

Abatacept↗

Performance of tPSA and f/tPSA for prostate cancer in Chinese. A systematic review and meta-analysis.

Performing a systematic review and meta-analysis to evaluate the diagnostic performance of the total prostate-specific antigen (tPSA) tests for diagnosis of prostate cancer among Chinese. Literatures related to diagnosis of prostate cancer by tPSA and the ratio of free to total PSA (f/tPSA) being retrieved in five electronic databases. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) were pooled using random effects models. Summary receiver operating characteristic curves (SROC) used to summarize overall test performance. In total 10 studies meeting the inclusion criteria, 2256 patients were included. Among them 423 were patients of prostate cancer compared to 1833 were patients of benign prostate hyperplasia (BPH). The pooled sensitivity and specificity of tPSA>4.0 ng/ml, tPSA>10.0 ng/ml and f/tPSA<0.15 as threshold for the diagnosis of prostate cancer were heterogeneity. The areas under SROC (AUC) were 80, 85 and 87%, respectively (P<0.05). The pooled DOR were 8.44(95%CI: 4.45 approximately 16.00), 9.94(95%CI: 4.15 approximately 23.77) and 13.75(95%CI: 6.35 approximately 29.76), respectively (P<0.05). chi(2) test used for testing the heterogeneity. tPSA and f/tPSA made an important performance for diagnosis of prostate cancer in decade among Chinese. The use of f/tPSA<0.15 as threshold maintain a high prognostic accuracy for prostate cancer.

Asian People↗

Salmonellosis outbreak among factory workers--Huizhou, Guangdong Province, China, July 2004.

INTRODUCTION: During July 9--14, 2004, an outbreak of gastroenteritis occurred among workers at an electronics factory in Huizhou, Guangdong Province, China; 199 cases were reported. A case-control investigation was initiated to identify the agent and the mode of transmission. METHODS: Stool samples were collected from 142 workers and food handlers and cultured for enteric pathogens. A questionnaire concerning meals and foods eaten in the factory cafeteria during July 11--13 was administered to 92 ill workers and 100 controls. RESULTS: Of approximately 2,000 workers who worked during the outbreak, 197 (10%) had illness consistent with the case definition. Salmonella enteritidis was identified from 44 (31%) of 142 stool samples collected from ill workers. Ill workers were more likely than controls to have eaten breakfast in the factory cafeteria during July 11--13. Of eight foods served at breakfast in the factory cafeteria, three were associated with illness: cake, bread (on July 12 only), and congee (i.e., rice porridge). Stratification of bread and congee exposure by cake consumption indicated that only bread eaten on July 12 was associated with gastroenteritis. The cake was baked on July 11, and a mixture that included raw eggs was poured on top; the cake was then stored at room temperature and served for breakfast on 3 consecutive days (July 11--13). The bread was stored together with the cake on July 11 and 12. No leftover food was tested. DISCUSSION: The investigation indicated that an outbreak of S. enterica serotype Enteritidis resulted from consumption of an unusual food vehicle (i.e., cake) that had been contaminated from a more typical source (i.e., raw eggs). The bread was stored at room temperature together with cake on which a mixture made from raw eggs had been poured. The bread was probably contaminated by contact with the cake. CONCLUSION: Food handlers should be instructed that intact fresh eggs can harbor S. enteritidis, foods made from eggs must be cooked, and prepared food must be stored under refrigeration.

Case-Control Studies↗

Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation.

BACKGROUND: Warfarin is a mainstay of therapy for conditions associated with an increased risk of thromboembolic events. However, the use of this common agent is fraught with complications and little is known regarding inter-individual variation in warfarin response. OBJECTIVE: We tested for association between single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 and average weekly warfarin dose required to maintain patients at their desired anticoagulation target. METHODS: The sample consisted of 93 European-American patients from anticoagulation clinics at the University of North Carolina at Chapel Hill. Data on mean weekly warfarin dose were collected over a mean treatment period of 20.6 months. ANCOVA models were used and haplotype analysis was performed. RESULTS: Three of six VKORC1 SNPs were found to be very strongly associated with the average warfarin dose required to achieve the target international normalised ratio (INR; p<0.0001). The mean weekly dose by genotype ranged from approximately 27 to 47 mg. There was no evidence for an association between either of the two CYP2C9 polymorphisms studied, CYP2C9*2 and CYP2C9*3. CYP2C9*3 was significantly (p = 0.05) associated with average warfarin dosage after adjustment for VKORC1*1173. CONCLUSIONS: These results are of considerable clinical interest and confirm recently published results regarding the role of these two genes in modifying warfarin metabolism and maintenance dosage. The consistent findings regarding the role of VKORC1 and CYP2C9 in warfarin metabolism and maintenance dosage represent a clinically useful proof of principal for the use of pharmacogenomic information in medicine and may lead to improved understanding of warfarin's actions.

Adult↗

An approach of encoding for prediction of splice sites using SVM.

In splice sites prediction, the accuracy is lower than 90% though the sequences adjacent to the splice sites have a high conservation. In order to improve the prediction accuracy, much attention has been paid to the improvement of the performance of the algorithms used, and few used for solving the fundamental issues, namely, nucleotide encoding. In this paper, a predictor is constructed to predict the true and false splice sites for higher eukaryotes based on support vector machines (SVM). Four types of encoding, which were mono-nucleotide (MN) encoding, MN with frequency difference between the true sites and false sites (FDTF) encoding, Pair-wise nucleotides (PN) encoding and PN with FDTF encoding, were applied to generate the input for the SVM. The results showed that PN with FDTF encoding as input to SVM led to the most reliable recognition of splice sites and the accuracy for the prediction of true donor sites and false sites were 96.3%, 93.7%, respectively, and the accuracy for predicting of true acceptor sites and false sites were 94.0%, 93.2%, respectively.

Algorithms↗

Genetic variation in the hepatic lipase gene and the risk of coronary heart disease among US diabetic men: potential interaction with obesity.

AIMS/HYPOTHESIS: The -514 C to T polymorphism of the hepatic lipase gene (LIPC) has been associated with lowered LIPC activity and elevated HDL-cholesterol concentrations. Previous findings on the association of this polymorphism with the risk of CHD are inconsistent. Moreover, data on this association among diabetic patients are limited. We investigated the association of the LIPC polymorphism with CHD risk among US diabetic men and evaluated whether this association was modified by adiposity status. SUBJECTS AND METHODS: The case group consisted of 220 diabetic men who were recruited from the Health Professionals Follow-up Study (years 1986-2000) and were free of cardiovascular disease at baseline, but subsequently developed CHD. A total of 641 diabetic men from the same study but without cardiovascular disease constituted the control group. RESULTS: No overall association between the LIPC polymorphism and CHD risk was observed. However, we did observe a significant interaction between this polymorphism and BMI in association with CHD risk. Among obese men, after adjustment for age, duration of diabetes and major lifestyle factors, the CT or TT genotype was associated with an increased CHD risk compared with the CC genotype (odds ratio [OR] 2.52, 95% CI 1.08-5.90); the corresponding ORs (95% CI) were 0.99 (0.58, 1.69) for overweight men (25< or =BMI <30 kg/m(2)) and 0.37 (0.17, 0.79) for lean men (BMI <25 kg/m(2)) (p for interaction 0.001). Stratified analyses by waist circumference (tertiles) showed a similar pattern of interaction (adjusted p for interaction 0.023). CONCLUSION/INTERPRETATION: These data suggest that obesity may modify the association between the LIPC C(-514)T polymorphism and CHD risk among diabetic men.

Adult↗

Improved health-related quality of life for rheumatoid arthritis patients treated with abatacept who have inadequate response to anti-TNF therapy in a double-blind, placebo-controlled, multicentre randomized clinical trial.

OBJECTIVE: Rheumatoid arthritis (RA) patients who have inadequate response to anti-tumour necrosis factor (TNF) therapy currently have treatment options that are limited and less than optimal in their risk-to-benefit ratio. Abatacept provides a new generation of RA medications that has previously been demonstrated to have positive clinical outcomes with this population. The current study sought to demonstrate the efficacy of abatacept on quality of life (QoL) for RA patients with inadequate response to anti-TNF therapy. METHODS: Patients were entered into a double-blind, placebo-controlled, multicentre randomized clinical trial, with 258 patients randomized to abatacept + disease-modifying anti-rheumatic drugs (DMARDs) and 133 patients randomized to placebo + DMARDS. The QoL was measured with the Short Form Health Survey (SF-36), Health Assessment Questionnaire (HAQ) and fatigue visual analogue scale, and was analysed with basic (ANOVA, chi-square) and multigroup growth curve techniques to assess differential change over time. RESULTS: Treatment group QoL improved significantly more than placebo on the HAQ and fatigue indices, as well as seven of the eight SF-36 scales and SF-36 physical and mental summary scores. Improvement rate was faster for abatacept than for placebo on the QoL measures, and the improvements from abatacept related to normal levels of QoL on many domains. CONCLUSION: Clinically relevant benefits of abatacept over placebo are discussed regarding improving QoL. Importantly, the larger rate of change for abatacept over placebo provides clinicians with a medication that can lead to meaningful changes in a patient's life within a few weeks, even when the patient previously failed anti-TNF therapy.

Abatacept↗

Surgery for nonarteritic anterior ischemic optic neuropathy.

BACKGROUND: Nonarteritic ischemic optic neuropathy is characterized by sudden and painless loss of vision in the eye, accompanied by pallid swelling of the optic disc. No medical therapy has been proven effective in treating this condition. OBJECTIVES: The objective of this review is to assess the safety and efficacy of surgery compared with other treatment or usual care in people with nonarteritic ischemic optic neuropathy. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Group Trials Register, in The Cochrane Library, MEDLINE, EMBASE and the UK National Research Register (NRR). The last search was on 13 July 2005. SELECTION CRITERIA: We included randomized controlled trials. DATA COLLECTION AND ANALYSIS: We obtained full copies of all potentially relevant articles. One randomized trial was eligible for inclusion. One author extracted data which was verified by another author. No synthesis was required. MAIN RESULTS: The one included trial randomized 258 participants and was stopped early. At the time of the 24-month report the follow-up rate was 95.3% for six months and 67.4% for 24 months (174 participants, 89 careful follow up and 85 surgery). There was no evidence of a benefit of surgery on visual acuity. At six months 32.0% of the surgery group had improved visual acuity by three or more lines compared with 42.6% of the careful follow up group (unadjusted risk ratio (RR) 0.75, 95% confidence interval (CI) 0.54 to 1.04). At 24 months 29.4% of the surgery group had improved compared with 31.0% of the careful follow up group (unadjusted RR 0.95, 95% CI 0.60 to 1.49). Participants who underwent surgery had a greater risk of losing three or more lines of vision. At six months 18.9% in the surgery group had worsened compared with 14.8% in the careful follow up group (RR 1.28; 95% CI 0.73 to 2.24). At 24 months 20.0% in the surgery group had worsened compared with 21.8% in the careful follow up group (RR 0.92; 95% CI 0.51 to 1.64). AUTHORS' CONCLUSIONS: Results from the single trial indicate no evidence of a beneficial effect of optic nerve decompression surgery for nonarteritic ischemic optic neuropathy.

Humans↗

Induction of interleukin-6 release from monocytes by serine proteinases and its potential mechanisms.

Serine proteinases have been recognized playing an important role in inflammation via proteinase-activated receptors (PAR). However, little is known of the influence of serine proteinases and PAR on interleukin-6 (IL-6) secretion from highly purified monocytes. We challenged monocytes from human peripheral blood with serine proteinases and agonist peptides of PAR and measured the levels of IL-6, IL-1beta and IL-12 in culture supernatants by enzyme-linked immunosorbent assay. The results showed that thrombin, trypsin, tryptase and elastase stimulated approximately up to 2.9-, 2.0-, 1.8- and 2.1-fold increase in IL-6 release from monocytes following 16 h of incubation, respectively. Proteinase inhibitors inhibited the actions of proteinases on monocytes. Agonist peptides of PAR-1 (SFLLR-NH(3)) and PAR-4 (GYPGQV-NH(2)), but not PAR-3 (TFRGAP-NH(2)), also induced IL-6 release from monocytes. The proteinases and agonists of PAR failed to stimulate IL-1beta and IL-12 secretion. In conclusion, the induction of IL-6 secretion by serine proteinases may be through the activation of PAR.

Blood Cells↗

Karyotypic evolution of the family Sciuridae: inferences from the genome organizations of ground squirrels.

Cross-species chromosome painting has made a great contribution to our understanding of the evolution of karyotypes and genome organizations of mammals. Several recent papers of comparative painting between tree and flying squirrels have shed some light on the evolution of the family Sciuridae and the order Rodentia. In the present study we have extended the comparative painting to the Himalayan marmot (Marmotahimalayana) and the African ground squirrel (Xerus cf. erythropus), i.e. representative species from another important squirrel group--the ground squirrels--, and have established genome-wide comparative chromosome maps between human, eastern gray squirrel, and these two ground squirrels. The results show that 1) the squirrels so far studied all have conserved karyotypes that resemble the ancestral karyotype of the order Rodentia; 2) the African ground squirrels could have retained the ancestral karyotype of the family Sciuridae. Furthermore, we have mapped the evolutionary rearrangements onto a molecular-based consensus phylogenetic tree of the family Sciuridae.

Animals↗

Chromosomal mechanisms underlying the karyotype evolution of the oriental voles (Muridae, Eothenomys).

We have investigated the karyotype relationships of two oriental voles, i.e. the Yulong vole (Eothenomys proditor, 2n = 32) and the large oriental vole (Eothenomys miletus, 2n = 56) as well as the Clarke's vole (Microtus clarkei, 2n = 52), by a combined approach of cross-species chromosome painting and high-resolution G-banding comparison. Chromosome-specific painting probes were generated from flow-sorted chromosomes of E. proditor and hybridized onto metaphases of E. proditor, E. miletus and M. clarkei, leading to the establishment of genome-wide comparative chromosome maps. Our results demonstrate that Robertsonian translocations (centric fusions) have played a major role in the karyotype evolution of oriental voles with no obvious evidence for the involvement of tandem fusions as proposed previously and that the genome organizations of vole species are highly conserved. The comparative chromosome maps of these three vole species belonging to two phylogenetically distinct genera provide a framework for future studies on the karyotype evolution in voles.

Animals↗

Prevalence of subclinical infection and transmission of severe acute respiratory syndrome (SARS) in a residential care home for the elderly.

OBJECTIVE: To ascertain the prevalence of subclinical severe acute respiratory syndrome-coronavirus (SARS-CoV) infection and study the transmission of SARS-CoV in a local outbreak at a residential care home for the elderly. DESIGN: Cross-sectional study. SETTING: A residential care home for the elderly in Hong Kong with a local outbreak of SARS. PARTICIPANTS: Residents and staff in the residential care home who had contact with three patients with SARS (residents A and B, and staff C). MAIN OUTCOME MEASURES: Blood samples were tested for total antibodies to SARS-CoV by immunofluorescence antibody test. The transmission of SARS was elucidated based on information from standardised questionnaires, and records of investigation and surveillance by the Department of Health. RESULTS: Among the 90 eligible residents, three died, one moved out, and 19 refused to participate. Of the 32 eligible staff, six refused to participate. None of the remaining 93 participants tested positive for antibody to SARS-CoV. Based on the chronological order, resident A might have transmitted infection to resident B and staff C. Sitting close to the bathroom doorway while resident A took a shower was the only contact of resident B with resident A. The only opportunity for staff C to have contact with body fluids/excreta of resident A was in the handling of rubbish from the resident's room. CONCLUSION: Subclinical SARS-CoV infection was rare in a residential care home for the elderly with an outbreak of SARS. Nonetheless the close working and living conditions for staff and residents in such a home may facilitate transmission of SARS despite vigilant precautionary measures.

Adult↗

Motion correction for improved target localization with on-board cone-beam computed tomography.

On-board imager (OBI) based cone-beam computed tomography (CBCT) has become available in radiotherapy clinics to accurately identify the target in the treatment position. However, due to the relatively slow gantry rotation (typically about 60 s for a full 360 degrees scan) in acquiring the CBCT projection data, the patient's respiratory motion causes serious problems such as blurring, doubling, streaking and distortion in the reconstructed images, which heavily degrade the image quality and the target localization. In this work, we present a motion compensation method for slow-rotating CBCT scans by incorporating into image reconstruction a patient-specific motion model, which is derived from previously obtained four-dimensional (4D) treatment planning CT images of the same patient via deformable registration. The registration of the 4D CT phases results in transformations representing a temporal sequence of three-dimensional (3D) deformation fields, or in other words, a 4D model of organ motion. The algorithm was developed heuristically in two-dimensional (2D) parallel-beam geometry and extended to 3D cone-beam geometry. By simulations with digital phantoms capable of translational motion and other complex motion, we demonstrated that the algorithm can reduce the motion artefacts locally, and restore the tumour size and shape, which may thereby improve the accuracy of target localization and patient positioning when CBCT is used as the treatment guidance.

Algorithms↗

Comparison of the survival of human biopsied embryos after cryopreservation with four different methods using non-transferable embryos.

BACKGROUND: The standard embryo cryopreservation method is still less than optimal for biopsied embryos. The aim of this study was to compare the survival of biopsied embryos cryopreserved with four different methods using non-transferable embryos. METHODS: Abnormal embryos from one or three pronuclei and spare embryos of grade 3 and 4 were used for this study. Non-biopsied embryos were cryopreserved using the standard method as control. Biopsied embryos were cryopreserved using four methods as follows: standard method, modified freezing method, modified thawing method and vitrification. Blastomere survival and blastulation of frozen-thawed embryos were compared between the different methods. RESULTS: The proportion of embryos with > or = 50% blastomere survival and total blastomere survival rate of biopsied embryos were significantly higher with vitrification than the other three methods. Both the modified freezing and modified thawing methods had significantly higher embryo survival and total blastomere survival rates than standard methods. However, there was no significant difference in blastulation of surviving embryos in all the five groups. CONCLUSIONS: Non-transferable embryos derived from clinical IVF/ICSI are useful for evaluation of the optimal freezing procedures for biopsied embryos. Vitrification increases the survival rate of human biopsied embryos above standard and modified cryopreservation methods.

Biopsy↗

IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women.

Elevated levels of the inflammatory cytokine IL-6 are associated with the development of disability, frailty, and mortality in older adults. These outcomes are likely mediated through inflammatory activity that alters hormones, skeletal muscle, and the immune system. Polymorphic variants in the IL-6 gene influence IL-6 expression. We hypothesized that IL-6 alleles associate with increased serum of IL-6, decreased muscle strength, and frailty, and tested this in the Women's Health and Aging cohorts. We genotyped 463 participants age 70-79, and identified three common IL-6 haplotype blocks for the Caucasian (n=363) and African American (n=100) subsets. Using linear and logistic regression, and adjusting for age, BMI, race, and osteoarthritis, we identified no significant or clinically meaningful relationship between any single IL-6 single nucleotide polymorphism (SNP) or any IL-6 haplotype and serum IL-6 level, grip, knee, or hip strength, or frailty. Given that the promoter SNP (rs1800795) has been reported to influence IL-6 levels and health outcomes, we performed a similar association study in the In Chianti population (n=266) and confirmed lack of association. These results suggest that IL-6 gene variation may not be an important factor in the determination of elevated IL-6 levels and related phenotypes found in older women.

Aged↗

Transfection of CD40Ig into liver prevents acute rejection in rat liver transplantation.

OBJECTIVE: To investigate the effect of CD40Ig upon acute rejection of rat liver transplants. METHODS: Thirty-two orthotopic liver transplants were performed using Lewis to BN rats with "the two-cuff technique". The rats were randomly divided into three groups. Group A served as controls (n = 10); group B (n = 11) and group C (n = 11); Lipofectamine2000-pcDNA3.1 or Lipofectamine2000-pcDNA3.1. CD40Ig complex was injected into Lewis portal vein ex vivo before cold storage of the liver. On the fifth day after transplantation, three rats in each group were killed to study the pathological changes and TUNEL immune histochemistry performed to examine CD40Ig expression. Lymphocytes were obtained from the spleen. The mixed lymphocyte reaction (MLR) was performed to determine tolerance and sheep anti-human immunoglobulin G (IgG)-FITC-labeled T cells counted by flow cytometry. Postoperative survival times of rats in each group were recorded. The pathological changes of dead rats were observed. RESULTS: The mean survival times of group A and B were 11.00 +/- 4.28 and 12.75 +/- 5.57 days, respectively. There were serious acute rejections in allograft liver in groups A and B. Apoptosis index was 33.67 +/- 5.69 versus 39.00 +/- 5.29. Group C mean survival time was 41.25 +/- 13.70 days (P < .01). Immune histochemistry showed CD40Ig-positive elements in the allograft liver, which revealed light acute rejection and apoptosis index was 0.27 +/- 0.21 (P < .01). The part of the allografted liver in a dead rat showed light acute rejection while the others displayed chronic rejection. Recipients were specifically tolerant to donors in the MLR assay. The IgG-FITC-labeled T cells accounted for 11.57% of all T cells in group C. CONCLUSIONS: CD40Ig transfection inhibited T-cell costimulatory pathway, prevented acute rejection, and prolonged graft survival.

Animals↗