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Biomedical subjects

L Wei

Publications and source records attributed to L Wei.

At least 19 recordsLinked to original sources
PubMed2007

Effectiveness of two statin prescribing strategies with respect to adherence and cardiovascular outcomes: observational study.

BACKGROUND: There is considerable evidence that statins can reduce cardiovascular events. Currently high-risk patients are treated to a target cholesterol concentration. An alternative prescribing strategy (the 'fire-and-forget' approach) would instead deploy low-dose statins more widely. It has been suggested that for the same cost this approach might prevent more cardiovascular events. We have compared the treat-to-target and fire-and-forget statin prescribing strategies with respect to adherence and cardiovascular outcomes. METHODS: We used a population-based record-linkage database containing several data sets linked by a unique patient identifier. We identified two cohorts of patients. Patients in the treat-to-target cohort were prescribed a statin, and subsequent measurement of their cholesterol was followed by upward titration of their statin dose if necessary. Patients in the fire-and-forget cohort were prescribed a statin, but no further cholesterol measurement was observed during the follow-up period. FINDINGS: Adherence to statin treatment in patients treated to target was significantly better than in patients treated on a fire-and-forget basis (adjusted odds ratio 2.51, 95%CI 2.26-2.78). We found a lower cardiovascular disease (CVD) event rate in patients treated to target than in fire-and-forget patients (hazard ratio of CVD or cardiovascular death 0.41 (0.35-0.48) even after adjustment was made for adherence and baseline CVD risk). INTERPRETATION: Our findings suggest that adherence to statins is worse in patients treated on a fire-and-forget basis than in patients treated to a target cholesterol concentration, and that this prescribing strategy is associated with worse cardiovascular outcomes.

Cardiovascular Diseases↗
PubMed2006

Long-term antibiotics for preventing recurrent urinary tract infection in children.

BACKGROUND: Acute urinary tract infection (UTI) is common in children. By the age of seven 8.4% of girls and 1.7% of boys will have suffered at least one episode. Symptoms include fever, lethargy, anorexia, and vomiting. UTI is caused by Escherichia coli in over 80% of cases and treatment consists of a course of antibiotics. Due to acute illness caused by UTI and the risk of pyelonephritis-induced permanent kidney damage, many children are given long-term antibiotics aimed at preventing recurrence. OBJECTIVES: To determine the efficacy and harms of long-term antibiotics to prevent recurrent UTI in children. SEARCH STRATEGY: We searched without language restriction MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, the Cochrane Renal Group's Specialised Register, reference lists of review articles and contacted content experts. Date of most recent search: January 2006 SELECTION CRITERIA: Randomised comparisons of antibiotics with other antibiotics, placebo or no treatment to prevent recurrent UTI. DATA COLLECTION AND ANALYSIS: Two authors independently assessed and extracted information. A random-effects model was used to estimate relative risk (RR) and risk difference (RD) for recurrent UTI with 95% confidence intervals (CI). MAIN RESULTS: Eight studies (618 children) were identified, five (406) comparing antibiotics with placebo/no treatment. The duration of antibiotic prophylaxis treatment varied from 10 weeks to 12 months. Compared to placebo/no treatment, antibiotics reduced the risk of repeat positive urine culture (RR 0.44, 95% CI 0.19 to 1.00; RD -30%, 95% CI -56% to -4%) No side effects were reported. One study reported that nitrofurantoin was more effective than trimethoprim in preventing recurrent UTI over a six month period (RR 0.48, 95% CI 0.25 to 0.92; RD -18%, 95% CI -34% to -3%). However, patients receiving nitrofurantoin were more likely to discontinue the antibiotic due to side effects (mainly gastrointestinal) (RR 3.17, 95% CI 1.36 to 7.37; RD 22%, 95% CI 8% to 36%). The other study found cefixime was more effective in preventing recurrent UTI than nitrofurantoin (RR 0.74, 95% CI 0.13 to 4.10; RD -3%, 95% CI -17% to -12%). However, 62% of patients receiving cefixime experienced an adverse reaction during the first six months of treatment (18/29) while only 26% (8/31) of patients receiving nitrofurantoin reported an adverse reaction. AUTHORS' CONCLUSIONS: Large, properly randomised, double blinded studies are needed to determine the efficacy of long-term antibiotics for the prevention of UTI in susceptible children.

Acute Disease↗
PubMed2006

Free radical-mediated neurotoxicity may be caused by inhibition of mitochondrial dehydrogenases in vitro and in vivo.

We previously demonstrated that copper facilitated the formation of reactive oxygen species, and inhibited pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase in vitro and in animal models of Wilson's disease in vivo. However, direct Cu(2+) toxicity has only been demonstrated for Wilson's disease. We now hypothesize that inhibition of these mitochondrial dehydrogenases might also contribute to many other injuries and disorders that are reactive oxygen species-mediated. We have modeled reactive oxygen species-mediated injuries using inducers of reactive oxygen species such as hydrogen peroxide, ethacrynic acid or menadione, or another redox active metal (Cd(2+)). Here we demonstrated that these toxic exposures were accompanied by an early marked reduction in both pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase activities, followed by a decrease in neuronal mitochondrial transmembrane potential and ATP, prior to murine cortical neuronal death. Thiamine (6 mM), and dihydrolipoic acid (50 microM), required cofactors for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase (thiamine as thiamine pyrophosphate), attenuated the reactive oxygen species-induced reductions in these enzyme activities, as well as subsequent loss of mitochondrial transmembrane potential and ATP, and neuronal death. We next tested the effect of thiamine supplementation on an in vivo model of reactive oxygen species-mediated injury, transient middle cerebral artery occlusion, and reperfusion in rats. Oral or i.p. thiamine administration reduced the middle cerebral artery occlusion-induced infarct. These data suggest that reactive oxygen species-induced neuronal death may be caused in part by reactive oxygen species-mediated inhibition of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase in vitro and in vivo, and that thiamine or dihydrolipoic acid may constitute potential therapeutic agents not just against Cu(2+) neurotoxicity, but may reduce neuronal degeneration in the broader range of diseases mediated by free radical stress.

Adenosine Triphosphate↗
PubMed2006

Age-related neural degeneration in nuclear-factor kappaB p50 knockout mice.

Nuclear factor-kappaB is a transcription factor that regulates a variety of genes involved not only with immune and inflammatory responses, but also in cell survival. Nuclear-factor kappaB in the CNS is an area of current research interest; however, its role in age-related neural degeneration is obscure. The present study examines developmental degeneration changes in wild type and nuclear factor-kappaB p50 subunit knockout mice (p50-/-) using various morphological methodologies. P50-/- mice appeared normal at birth. At 6 and 10 months old, the body weight of p50-/- mice was significantly less than that of wild type mice and they started to die from aging. Consistently, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling positive cells in the cortex were significantly more in p50-/- mice than that in wild type mice, and neuronal cells in the cortex, hippocampus and caudate nucleus-putamen decreased in p50-/- mice. Fewer myelinated axons of the optic nerve were found in p50-/- mice than in wild type mice at 6 months. In p50-/- mice, morphological examinations showed: 1) aging and degenerative changes in the cortex and hippocampus including increased lipofuscin granules in neural cytoplasm, 2) abnormal capillaries, 3) dark and watery alterations and organelle accumulations, 4) apoptotic glia cells, and 5) terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling and caspase-3 positive neurons. These results suggest that nuclear-factor kappaB may play an important role in neurovascular development, cell survival, and the aging process in the CNS. This new evidence linking nuclear-factor kappaB to myelination and aging may be of considerable importance for several areas of basic and clinical neuroscience.

Aging↗
PubMed2006

Hematopoietic stem cell mobilization after rat partial orthotopic liver transplantation.

BACKGROUND: On the basis of the recently recognized potential of hematopoietic stem cells (HSC) to give rise to hepatocytes, we investigated the possibility that HSC could be mobilized and home to the injured liver promoting tissue repair after 50% partial orthotopic liver transplantation (PLTx) in the rat. METHODS: Using sex-mismatched (female to male) syngeneic SD rats, we performed 50% PLTx or whole orthotopic liver transplantation (WLTx) versus 50% partial hepatectomy (PHx) and sham operation (O). Elements with stem cell markers were detected in peripheral blood (PB) and in the liver. Liver injury and regeneration were estimated. The sex-determining region for Y chromosome gene (SRY) was used to define cell origin by in situ hybridization in liver sections. RESULTS: Comparison of WLTx and PHx groups showed a lower survival rate (50%), in the PLTx group were (P<.05). Further, the liver injury was more serious and the levels of serum biochemical parameters were higher. Compared with PHx groups, on days 3 and 5 postoperatively, the mitosis index and the expression of PCNA were lower among the PLTx groups. Compared with WLTx and sham operation groups, beta2m-/Thy-1.1+, CD34+ cells in PB in PLTx groups and PHx were increased on day 1 postoperatively and decreased on the following days. Compared with PHx groups, beta2m-/Thy-1.1+, CD34+ cells were higher in PLTx. The CD34-, c-kit-, and Thy-1.1-positive cells detected in portal tract areas peaked during 3 to 5 days postoperatively in PLTx. Few SRY+ cells were detected in PLTx liver grafts. CONCLUSIONS: beta2m-/Thy-1.1+ and CD34+ stem cells mobilized after PLTx and PHx may be related to the reduced-size liver. Few HSC are involved in liver regeneration in PLTx.

Animals↗
PubMed2006

Differentiation of hematopoietic stem cells into hepatocytes in liver fibrosis in rats.

It has been reported that hematopoietic stem cells (HSC) can differentiate into hepatocytes in the normal liver and in some pathologic environments. The aim of this study was to investigate whether HSC can differentiate into hepatocytes in cases of established liver fibrosis. Rat liver fibrosis was induced by subcutaneous injection of tetrachloride (CCl4). Thy+ CD3- CD45RA- HSC in bone marrow cells, which had been enriched by fluorescence-activated cell sorting (FACS), were labeled with PKH26-GL, and autologously transplanted into CCl4-treated rats. The expressions of albumin (Alb), cytokeratin 8 (CK8), and alpha-smooth muscle actin (SMA) were determined by immunofluorescence methods. The PKH26-GL labeled Thy+ CD3- CD45RA- HSC expressed the hepatocyte-specific markers Alb and CK8, but did not express alpha-SMA in liver fibrosis. Thy+ CD3- CD45RA- HSC differentiated into hepatocytes, but not into hepatic stellate cells. In conclusion, autologous stem cell transplantation may be helpful to treat hepatic fibrosis.

Animals↗
PubMed2005

Impact on cardiovascular events of increasing high density lipoprotein cholesterol with and without lipid lowering drugs.

OBJECTIVE: To estimate the impact on cardiovascular events of changes in high density lipoprotein (HDL) adjusted for changes in total cholesterol. DESIGN: Cohort study based on a record linkage database. SETTING: Community study in Tayside, Scotland, UK. PATIENTS: 18,815 patients were identified for the study between 1989 and 2001. MAIN OUTCOME MEASURES: Cardiovascular events. RESULTS: 5510 patients taking lipid lowering treatment who had not been hospitalised previously for cardiovascular disease had 314 cardiovascular events recorded (9407 person years of follow up). Patients whose HDL rose by > 20% were less likely to have an event (23.5/1000 person years, 95% confidence interval (CI) 17.3 to 29.6) compared with patients whose HDL did not rise (42.6/1000 person years, 95% CI 35.5 to 49.7, adjusted relative risk 0.60, 95% CI 0.44 to 0.83). HDL change and cardiovascular outcome were not significantly associated among patients who had been hospitalised previously for cardiovascular disease or among patients who were not taking lipid lowering drugs. CONCLUSION: In this study a rise in HDL independently predicted reduced cardiovascular risk in patients taking lipid lowering treatment who had not been hospitalised previously for cardiovascular disease.

Cardiovascular Diseases↗
PubMed2005

Matrix metalloproteinase stromelysin-3 in development and pathogenesis.

The extracellular matrix (ECM) serves as a medium for cell-cell interactions and can directly signal cells through cell surface ECM receptors, such as integrins. In addition, many growth factors and signaling molecules are stored in the ECM. Thus, ECM remodeling and/or degradation plays a critical role in cell fate and behavior during many developmental and pathological processes. ECM remodeling/degradation is, to a large extent, mediated by matrix metalloproteinases (MMPs), a family of extracellular or membrane-bound, Zn2+-dependent proteases that are capable of digesting various proteinaceous components of the ECM. Of particular interest among them is the MMP11 or stromelysin-3, which was first isolated as a breast cancer associated protease. Here, we review some evidence for the involvement of this MMP in development and diseases with a special emphasis on amphibian metamorphosis, a postembryonic, thyroid hormone-dependent process that transforms essentially every organ/tissue of the animal.

Animals↗
PubMed2004

Presence of bacteriuria caused by trimethoprim resistant bacteria in patients prescribed antibiotics: multilevel model with practice and individual patient data.

OBJECTIVE: To look for evidence of a relation between antibiotic resistance and prescribing by general practitioners by analysis of prescribing at both practice and individual patient level. DESIGN: Repeated cross-sectional study in 1995 and 1996. SETTING: 28 general practices in the Ninewells Hospital laboratory catchment area, Tayside, Scotland. SUBJECTS REVIEWED: 8833 patients registered with the 28 practices who submitted urine samples for analysis. MAIN OUTCOME MEASURES: Resistance to trimethoprim in bacteria isolated from urine samples at practice and individual level simultaneously in a multilevel model. RESULTS: Practices showed considerable variation in both the prevalence of trimethoprim resistance (26-50% of bacteria isolated) and trimethoprim prescribing (67-357 prescriptions per 100 practice patients). Although variation in prescribing showed no association with resistance at the practice level after adjustment for other factors (P = 0.101), in the multilevel model resistance to trimethoprim was significantly associated with age, sex, and individual-level exposure to trimethoprim (P < 0.001) or to other antibiotics (P = 0.002). The association with trimethoprim resistance was strongest for people recently exposed to trimethoprim, and there was no association for people with trimethoprim exposure more than six months before the date of the urine sample. DISCUSSION: Analysis of practice level data obscured important associations between antibiotic prescribing and resistance. The results support efforts to reduce unnecessary prescribing of antibiotics in the community and show the added value of individual patient data for research on the outcomes of prescribing.

Adolescent↗
PubMed2004

Mapping OI-4, a gene conferring resistance to Oidium neolycopersici and originating from Lycopersicon peruvianum LA2172, requires multi-allelic, single-locus markers.

Lycopersicon peruvianum LA2172 is completely resistant to Oidium neolycopersici, the causal agent of tomato powdery mildew. Despite the large genetic distance between the cultivated tomato and L. peruvianum, fertile F1 hybrids of L. esculentum cv. Money maker x L.peruvianum LA2172 were produced, and a pseudo-F2 population was generated by mating F, half-sibs. The disease tests on the pseudo-F2 population and two BC,families showed that the resistance in LA2172 is governed by one dominant gene, designated as 01-4. In the pseudo-F2 population, distorted segregation was observed, and multi-allelic, single-locus markers were used to display different marker-allele configurations per locus. Para-meters for both distortion and linkage between genetic loci were determined by maximum likelihood estimation, and the necessity of using multi-allelic, single-locus markers was illustrated. Finally, a genetic linkage map of chromosome 6 around the 01-4 locus was constructed by using the pseudo-F2 population.

Ascomycota↗
PubMed2004

The survival and value of liver transplantation for liver carcinoma: a single-center experience.

UNLABELLED: Liver transplantation for liver carcinoma with cirrhosis is a treatment still in dispute. The objectives were to summarize the survival and cost of 50 liver transplant cases performed for liver carcinoma over nearly 3 years. METHODS: We performed 138 liver transplants from January 1999 to February 2002. There were 50 cases (36.2%) of liver carcinoma with HBV cirrhosis, which were divided into three stages based on the tumor pathology: Stage 1 cases showed a single mass (< or = 5 cm), 4 cases; Stage 2, a single mass > 5 cm or intrahepatic multiple masses without PV cancer embolus, 32 cases; and Stage 3: tumor invasion of the PV or perihepatic lymph nodes or organs, 14 cases. All patients received three to six courses of chemotherapy postoperatively. RESULTS: All four cases of stage 1 survived > 1 year; one of them is at 3 years with good liver function and tumor free. The mean half-year medical cost was $27.100 +/- 108 in stage 1. The half-year survival and medical costs were 62.5% and $31,500 +/- 260 in stage 2 and 15.0% and $35,500 +/- 134 in stage 3. CONCLUSION: Liver transplantation is an effective treatment for early-stage liver carcinoma, that achieves good medical and economic results, but should be limited to advanced liver cancer.

Analysis of Variance↗
PubMed2004

Effect of high-level natural radiation on chromosomes of residents in southern China.

To study the effect of low-dose (rate) radiation on human health, we analyzed chromosomes of peripheral lymphocytes of residents in a high background radiation area (HBRA) and compared the results with those obtained from residents in a control area (CA) in Guangdong Province, China. Unstable types of chromosome aberrations (dicentrics and rings) were studied in 22 members of eight families in HBRA and 17 members of five families in CA. Each family consists of three generations. On average 2,600 cells per subject were analyzed. 27 adults and six children in HBRA and 25 adults and eight children in CA were studied with respect to translocations. On average 4,741 cells per subject were examined. We found an increase of the frequency of dicentrics and rings in HBRA, where the natural radiation level is three to five times higher than in the control area. But the increase of translocations in HBRA was within the range of individual variation in the controls.

Adult↗
PubMed2004

From hemorheology to vascular mechanobiology: An overview.

Almost all of the cells of the human body are subjected to mechanical stresses. In endothelial cells, mechanical stresses can vary from some milli-Pascal (shear stress) to one ore more Pascal (hydrostatic pressure). Now it is know that mechanical stresses have a decisive part cellular physiology. However, if the main biological effects of mechanical stress are well related, the mechanisms allowed the relation between mechanical stress to physiological phenomenon remain nearly unknown (mechanotransduction phenomenon). In this work, through personal results and published works, the authors considers all the effects of mechanical stresses and the possible hypothesis.

Blood Vessels↗
PubMed2003

Magnesium deficiency: effect on bone mineral density in the mouse appendicular skeleton.

BACKGROUND: Dietary magnesium (Mg) deficiency in the mouse perturbs bone and mineral homeostasis. The objective of the present study was to evaluate bone mineral density of the femur in control and Mg-deficient mice. METHODS: BALB/c mice aged 28 days at study initiation were maintained on a normal or Mg deficient (0.0002% Mg) diet, and at time points 0, 2, 4 or 6 weeks bones were harvested for bone mineral density analysis. Peripheral quantitative computed tomography (pQCT) was used to assess the trabecular metaphyseal compartment and the cortical midshaft. RESULTS: Although mean total bone density of the femoral midshaft in Mg deficient mice did not differ significantly from controls throughout the study, the trabecular bone compartment showed significantly decreased mineral content after 4 (p < 0.001) and 6 weeks (p < 0.001) of Mg depletion. CONCLUSIONS: This study demonstrates the profound effect of Mg depletion on the trabecular compartment of bone, which, with its greater surface area and turnover, was more responsive to Mg depletion than cortical bone in the appendicular skeleton of the mouse.

Animals↗
PubMed2003

Effect of ibuprofen on cardioprotective effect of aspirin.

Treatment with ibuprofen might limit the cardioprotective effects of aspirin. We aimed to assess whether patients with known cardiovascular disease who take low-dose aspirin and ibuprofen have increased risk of cardiovascular mortality. We studied 7107 patients who were discharged after first admission for cardiovascular disease between April, 1989, and April, 1997, and who were prescribed low-dose aspirin (<325 mg/day) and survived for at least 1 month. Compared with those who used aspirin alone, patients taking aspirin plus ibuprofen had an increased risk of all-cause mortality (adjusted hazard ratio 1.93, 95% CI 1.30-2.87, p=0.0011) and cardiovascular mortality (1.73, 1.05-2.84, p=0.0305). Our finding lends support to the hypothesis that ibuprofen may interact with the cardioprotective effects of aspirin, at least in patients with established cardiovascular disease.

Adult↗
PubMed2003

Periocular injection of an adenoviral vector encoding pigment epithelium-derived factor inhibits choroidal neovascularization.

Gene transfer provides an exciting new approach for the treatment of retinal and choroidal diseases. Two areas of concern are the potential for vector-related toxicity and uncertainties associated with prolonged transgene expression. One way to address these concerns for transfer of genes encoding secreted proteins is to transduce cells on the outside of the eye, provided the gene product can gain access to the eye and have the desired effect. In this study, we investigated the feasibility of this approach. Periocular injection of an adenoviral vector encoding beta-galactosidase (AdLacZ.10) resulted in LacZ-stained cells throughout the orbit and around the eye. Compared to periocular injection of 5 x 10(9) particles of control vector, periocular injection of 5 x 10(9) or 1 x 10(9) particles of an adenoviral vector expressing pigment epithelium-derived factor (PEDF) regulated by a CMV promoter (AdPEDF.11) resulted in significantly elevated intraocular levels of PEDF and suppression of choroidal neovascularization. Periocularly injected recombinant PEDF was also found to diffuse through the sclera into the eye. Although similar experiments are needed in an animal with a human-sized eye, these data suggest that periocular gene transfer deserves consideration for the treatment of choroidal diseases.

Adenoviridae↗