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1.
Zhonghua Yu Fang Yi Xue Za Zhi ; 52(3): 277-281, 2018 Mar 06.
Article in Chinese | MEDLINE | ID: mdl-29973007

ABSTRACT

Objective: To explore drug resistance of different viral loads, and investigate the relationship between drug resistance and CD4(+)T cell counts in patients with HIV antiretroviral therapy (ART) in China from 2003 to 2015. Methods: Data were extracted from the Chinese National HIVDR Surveillance database from 2003 to 2015. For this study, the data collected were as follows: having received ART for ≥12 months; 18 years or older; demographic characteristics, information of ART, CD4(+)T cell counts, viral load (VL) and HIV drug resistance of a total of 8 362 patients were collected. Multi-variables non-conditional logistic regression model was used to study the relationship between viral load, HIV drug resistance and CD4(+)T cell counts. Results: Participants with age of (41.8±10.5) years were enrolled in this study. Among them, 59.9% (5 009 cases) were men. The percentage of CD4(+)T cell counts <200 cells/µl in the total population was 17.9% (1 496 cases), the highest was in VL ≥1 000 copies/ml with drug resistance, which was 43.0% (397/923) , followed by VL 50-999 copies/ml with drug resistance, which was 31.1% (69/222), and the lowest was in VL 50-999 copies/ml without drug resistance 13.2% (273/2 068). Compared to VL 50-999 copies/ml without drug resistance, VL<50 copies/ml, VL 50-999 with drug resistance, VL≥1 000 copies/ml without drug resistance, and VL ≥1 000 copies/ml with drug resistance, the OR (95%CI) of CD4 <200 cells/µl were 0.9 (0.7-1.0), 3.2 (2.3-4.4), 2.6 (2.1-3.2), and 4.9 (4.0-5.9), respectively. Among 222 patients with VL 50-999 and HIVDR, the most frequent antiretroviral drugs were EFV and NVP, both of which were NNRTI, and whose percentage both were 94.1% (209 cases). The most frequent mutations were M184V/I (NNRTI), and the percentage was 26.1% (58 cases). The second one was K103N (NNRTI), and the percentage was 22.5% (50 cases). The percentage of V32L/E (PI) and V82A (PI) were lower, they were 0.9% (2 cases) and 0.5% (1 case) respectively. Conclusion: Decreased CD4(+)T cell counts were associated with HIV drug resistance at low viraemia. In the case of low viral load, the most vulnerable were the NNRTI antiviral drugs such as EFV and NVP.


Subject(s)
Anti-HIV Agents/therapeutic use , Drug Resistance, Viral , HIV Infections/drug therapy , Adult , CD4 Lymphocyte Count/statistics & numerical data , China , Female , Humans , Male , Middle Aged , Viral Load/statistics & numerical data
2.
Hong Kong Med J ; 24(1): 18-24, 2018 02.
Article in English | MEDLINE | ID: mdl-29302019

ABSTRACT

INTRODUCTION: There are no recent data on nipple discharge and its association with malignancy in Hong Kong Chinese women. This study reported our 5-year experience in the management of patients with nipple discharge, and our experience of mammography, ultrasonography, ductography, and nipple discharge cytology in an attempt to determine their role in the management of nipple discharge. METHODS: Women who attended our Breast Clinic in a university-affiliated hospital in Hong Kong were identified by retrospective review of clinical data from January 2007 to December 2011. They were divided into benign and malignant subgroups. Background clinical variables and investigative results were compared between the two subgroups. We also reported the sensitivity, specificity, and positive and negative predictive values of the investigations that included mammography, ultrasonography, ductography, and cytology. RESULTS: We identified 71 and 31 patients in the benign and malignant subgroups, respectively. The median age at presentation for the benign subgroup was younger than that of the malignant subgroup (48 vs 59 years; P=0.003). A higher proportion of patients in the malignant subgroup than the benign subgroup presented with blood-stained nipple discharge (87.1% vs 47.9%; P=0.002). Mammography had a specificity of 98.4% and positive predictive value of 66.7%; ultrasonography had a specificity of 87.0% and negative predictive value of 75.0%. Cytology and ductography were sensitive but lacked specificity. Ductography had a negative predictive value of 100% but a low positive predictive value (14.0%). Clinical variables including age at presentation, duration of discharge, colour of discharge, presence of an associated breast mass, and abnormal sonographic findings were important in suggesting the underlying pathology of nipple discharge. Multiple logistic regression showed that blood-stained discharge and an associated breast mass were statistically significantly more common in the malignant subgroup. CONCLUSIONS: In patients with non-blood-stained nipple discharge, a negative clinical breast examination combined with negative imaging could reasonably infer a benign underlying pathology.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Nipple Discharge/cytology , Nipples/physiopathology , Adult , Aged , Aged, 80 and over , Cytological Techniques , Female , Hong Kong , Humans , Logistic Models , Mammography , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Ultrasonography , Young Adult
3.
Fa Yi Xue Za Zhi ; 33(2): 165-167, 2017 Apr.
Article in Chinese | MEDLINE | ID: mdl-29231024

ABSTRACT

OBJECTIVES: To detect diatom in the organs of drowners by enzyme combined with strong acid digestion method, and evaluate its application value. METHODS: A total of 40 cases which have been identified as drowning in local region were collected. Samples of the lung, liver, kidney, and the water of the scene were also gathered from each case. Strong acid digestion method, enzyme combined with strong acid digestion method, and enzymic digestion method were respectively performed to detect the diatom in the samples. The comparative analysis was made on digestion time, digestive power and detection rate of diatom, etc. RESULTS: Enzyme combined with strong acid digestion method was significantly better than enzymic digestion method on digestion time and digestive power; enzyme combined with strong acid digestion method were obviously superior to strong acid digestion method on the detection rate of diatom. CONCLUSIONS: Enzyme combined with strong acid digestion method combines the advantages of strong acid digestion method and enzymic digestion method. It has the characters of operation safety with little pollution to environment, which is worthy of further popularization and practice.


Subject(s)
Diatoms/isolation & purification , Drowning , Kidney/metabolism , Liver/metabolism , Lung/metabolism , Forensic Pathology/methods , Humans
4.
Hong Kong Med J ; 21(5): 426-34, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26139689

ABSTRACT

OBJECTIVE: To compare the safety, effectiveness, and outcomes of primary stenting and salvage stenting for malignant superior vena cava obstruction. DESIGN: Case series with internal comparison. SETTING: Regional hospital, Hong Kong. PATIENTS: A total of 56 patients with malignant superior vena cava obstruction underwent 59 stentings from 1 May 1999 to 31 January 2014. Patients' characteristics, procedural details, and outcomes were retrospectively reviewed. Of the 56 patients, 33 had primary stenting before conventional therapy and 23 had salvage stenting after failure of conventional therapy. Statistical analyses were made by Fisher's exact test and Mann-Whitney U test. RESULTS: Primary lung carcinoma was the most common cause of malignant superior vena cava obstruction (primary stenting, 22 patients; salvage stenting, 16 patients; P=0.768), followed by metastatic lymphadenopathy. Most patients had superior vena cava obstruction only (primary stenting, 16 patients; salvage stenting, 15 patients; P=0.633), followed by additional right brachiocephalic vein involvement. Wallstents (Boston Scientific, Natick [MA], US) were used in all patients. Technical success was achieved in all but two patients, one in each group (P=1.000). Only one stent placement was required in most patients (primary stenting, 28 patients; salvage stenting, 20 patients; P=0.726). Procedure time was comparable in both groups (mean time: primary stenting, 89 minutes; salvage stenting, 84 minutes; P=0.526). Symptomatic relief was achieved in most patients (primary stenting, 32 patients; salvage stenting, 23 patients; P=0.639). In-stent restenosis and bleeding were the commonest complications (primary stenting, 6 and 1 patients, respectively; salvage stenting, 2 and 2 patients, respectively). Nine patients required further treatment for symptom recurrence (primary stenting, 6 patients; salvage stenting, 3 patients; P=0.725). CONCLUSION: Endovascular stenting is safe and effective for relieving malignant superior vena cava obstruction. No statistically significant differences in number of stents, success rates, procedure times, symptom relief rates, complication rates, and re-procedure rates were found between primary stenting and salvage stenting.


Subject(s)
Carcinoma/complications , Neoplasms/complications , Neuroendocrine Tumors/complications , Salvage Therapy , Stents , Superior Vena Cava Syndrome/therapy , Aged , Aged, 80 and over , Endovascular Procedures/adverse effects , Female , Humans , Lymphoma/complications , Male , Middle Aged , Retrospective Studies , Stents/adverse effects , Superior Vena Cava Syndrome/etiology , Treatment Outcome
5.
Chem Commun (Camb) ; 51(52): 10447-50, 2015 Jul 04.
Article in English | MEDLINE | ID: mdl-26027701

ABSTRACT

Herein, we report the synthesis, structure, and electrochemistry of the first Na(+)-ion cathode with two distinct types of polyanions: Fe3P5SiO19. The Fe-based cathode has a reversible capacity of ca. 70 mA h g(-1); ca. 1.7 Na(+) ions per formula can be inserted/extracted at an average voltage of 2.5 V versus Na(+)/Na.

6.
Osteoporos Int ; 26(1): 187-97, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25112719

ABSTRACT

UNLABELLED: In this study, we found out a previously undefined function of icariin which restored the dynamic balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in patients with osteonecrosis of femoral head (ONFH) via ABCB1-promoter demethylation. These findings provided important information regarding potential implication of icariin targeting epigenetic changes for the treatment of steroid -associated ONFH. INTRODUCTION: Here, we investigated whether icariin can also exert a beneficial role in the reactivation of MSCs in the patients with steroid-associated ONFH via ABCB1-promoter demethylation. METHODS: Bone marrow was collected from the proximal femur in patients with steroid-associated ONFH (n = 20) and patients with new femoral neck fractures (n = 22), and then MSCs were isolated. We investigated cell viability, intracellular reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), P-glycoprotein (P-gp) activity, the transcript levels of ABCB1 and oxidative stress-related genes, methylation extent at CpG islands of ABCB1 promoter, and osteogenic and adipogenic differentiation ability of MSCs from the femoral neck fractures group and from the steroid-associated ONFH group treated with or without icariin. RESULTS: We observed that MSCs from the steroid-associated ONFH group showed reduced proliferation ability, elevated ROS level, depressed MMP, weakened osteogenesis, and enhanced adipogenesis while low P-gp activity, transcription level of ABCB1, and oxidative stress-related genes as well as aberrant CpG islands hypermethylation of ABCB1 were also noted in steroid-associated ONFH group. Treatment with icariin obviously induced de novo P-gp expression, decreased oxidative stress, and promoted osteogenesis. CONCLUSION: Icariin may be a potential drug targeting epigenetic changes for the treatment of steroid-associated ONFH.


Subject(s)
DNA Methylation/drug effects , Femur Head Necrosis/chemically induced , Flavonoids/pharmacology , Mesenchymal Stem Cells/drug effects , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Adipogenesis/drug effects , Adult , Aged , Cell Differentiation/drug effects , Cell Survival/drug effects , Cells, Cultured , Drug Evaluation, Preclinical/methods , Drugs, Chinese Herbal/pharmacology , Epigenesis, Genetic/drug effects , Female , Femur Head Necrosis/metabolism , Femur Head Necrosis/pathology , Glucocorticoids/adverse effects , Humans , Male , Membrane Potential, Mitochondrial/drug effects , Mesenchymal Stem Cells/metabolism , Middle Aged , Molecular Targeted Therapy/methods , Osteogenesis/drug effects , Promoter Regions, Genetic , Reactive Oxygen Species/metabolism
7.
Genet Mol Res ; 14(4): 19225-32, 2015 Dec 29.
Article in English | MEDLINE | ID: mdl-26782575

ABSTRACT

Osteoporosis is a common disease in the aging population and studies have shown that interleukin-6 (IL-6) is potentially implicated in its pathogenesis. This study was designed to assess the association between the IL-6 gene -634C/G polymorphism and osteoporosis. PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched for eligible studies published up to and including December 2014 in English or Chinese. Meta-analysis was conducted by the RevMan5.2 software. Weighted mean difference and 95% confidence interval (95%CI) were calculated by a fixed-effect or random-effect model. Bone mineral density (BMD) was regarded as the assessment index. As a result, a total of four articles with 3068 subjects were included. Differences in BMD between the CC and GG genotypes were 0.03 g/cm(2) (95%CI = 0.01 to 0.05) at total body, 0.01 g/cm(2) (95%CI = 0.00 to 0.03) at femoral neck, and 0.03 g/cm(2) (95%CI = 0.00 to 0.06) at the lumbar spine (P < 0.05). For the CG versus GG genotypes, the differences in BMD were 0.03 g/cm(2) (95%CI = 0.02 to 0.05) at total body and 0.02 g/cm(2) (95%CI = 0.00 to 0.03 at the femoral neck (P < 0.05). For the CC versus CG genotypes, the differences in BMD were not significant (P > 0.05). In conclusion, the GG genotype of the -634C/G polymorphism in IL-6 appears to play a role in reducing BMD, which affects normal bone metabolism and leads to osteoporosis.


Subject(s)
Bone Density/genetics , Interleukin-6/genetics , Osteoporosis/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Asian People , Female , Femur Neck/metabolism , Femur Neck/pathology , Gene Expression , Genotype , Humans , Interleukin-6/metabolism , Lumbar Vertebrae/metabolism , Lumbar Vertebrae/pathology , Male , Osteoporosis/diagnosis , Osteoporosis/ethnology , Osteoporosis/pathology
8.
Hum Exp Toxicol ; 31(11): 1170-8, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22736251

ABSTRACT

High doses of gadolinium-based contrast media are reported to induce deterioration of renal function. We assessed whether prophylactic 0.9% saline hydration inhibits high-dose gadodiamide-induced renal damage in rats. Twelve Sprague-Dawley rats were randomly divided into two groups, which are given gadodiamide (5 mmol/kg) with (hydration group) or without (control group) 0.9% saline hydration. The saline (4 mL/kg) was infused as a bolus into the peritoneum every 4 h, starting 12 h before and continuing for 12 h after the gadodiamide injection. Urine was collected to calculate creatinine clearance (Ccr) 24 h before and 48 h after the gadodiamide injection. The kidneys were harvested and stained for pathologic analysis. High-dose gadodiamide induced acute kidney injury as shown by decreased Ccr and renal histology with tubular cell injuries 48 h postinjection in both the groups. However, the extent of Ccr reduction was significantly (p = 0.02) less in the hydrated rats (-15% in the hydration group vs. -39% in the control group). Renal tubular cell injuries characterized by vacuolization, loss of brush borders, sloughing of tubular cells into the lumen, and flattening of the tubular epithelium were less frequently seen in the hydration group; only vacuolization (p = 0.01) and epithelial sloughing (p = 0.02) of the proximal tubules differed significantly between the two groups. We conclude that prophylactic 0.9% saline hydration significantly inhibited high-dose gadodiamide-induced nephropathy.


Subject(s)
Gadolinium DTPA/adverse effects , Kidney Diseases/prevention & control , Protective Agents/therapeutic use , Sodium Chloride/therapeutic use , Animals , Contrast Media/adverse effects , Creatinine/blood , Creatinine/urine , Fluid Therapy , Kidney Diseases/chemically induced , Kidney Diseases/metabolism , Kidney Diseases/pathology , Male , Rats , Rats, Sprague-Dawley
10.
J Hazard Mater ; 166(2-3): 1526-9, 2009 Jul 30.
Article in English | MEDLINE | ID: mdl-19168286

ABSTRACT

The effects of polyethyleneimine (PEI) impregnation on the Pb(2+) adsorption kinetics of palm shell-activated carbon and pH profile of bulk solution were investigated. Adsorption data were fitted to four established adsorption kinetics models, namely, pseudo-first-order, pseudo-second-order, Elovich equation and intraparticle diffusion. It was found that PEI impregnation at 16.68 and 29.82 wt% PEI/AC increased the Pb(2+) uptake rate while the opposite was observed for PEI impregnation at 4.76 and 8.41 wt% PEI/AC. The increased uptake rates were due to higher concentration of PEI molecules on the surface of clogged pores as well as varying pore volumes. The adsorption kinetics data fitted the pseudo-second-order model better than the pseudo-first-order model, implying chemisorption was the rate-controlling step. The bulk solution pH generally showed an increasing trend from the use of virgin to PEI-impregnated activated carbon.


Subject(s)
Charcoal/chemistry , Lead/isolation & purification , Polyethyleneimine/chemistry , Water Pollutants, Chemical/isolation & purification , Adsorption , Chelating Agents/chemistry , Cycadopsida/chemistry , Kinetics , Polymers/chemistry
11.
J Epidemiol Community Health ; 63(3): 209-14, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18812411

ABSTRACT

BACKGROUND: The Health Promoting School (HPS) approach provides a strong foundation to improve students' overall health, including psychological well-being, which has its roots in resilience. The present study evaluates the effectiveness of a resilience-enhancing programme, building on the concept of HPS among a Chinese population. METHODOLOGY: All mainstream schools in a socially disadvantaged region of Hong Kong were eligible, and stratified random sampling was used to recruit both HPS as intervention schools and non-HPS as control schools. The participants included teachers and parents of grade 3 and 5 primary and grade 1 secondary school students (aged 8, 10 and 12 respectively). Validated surveys were used to assess resilience scores in both groups of schools before and after a series of resilience-enhancing activities in HPS, and ANOVA was used to compare the score changes between the two groups. RESULTS: Five primary and four secondary HPS and four primary and four secondary non-HPS were recruited, involving 4918 parents and 602 teachers. Among primary and secondary parents, the HPS group did not report a higher score than the non-HPS group. Among secondary teachers, the HPS group showed significantly higher scores than the non-HPS group (p = 0.023 to < 0.001) CONCLUSION: The present study is the first to demonstrate the positive synergistic effect of a newly designed resilience-enhancing intervention programme, building on the concept of HPS in schools among secondary teachers in Hong Kong. It was suggested that future initiatives may involve parent networking and school-family collaboration in fostering an even more resilient school environment.


Subject(s)
Health Promotion/methods , Parents/psychology , Resilience, Psychological , Social Environment , Adult , Child , Faculty , Female , Hong Kong , Humans , Interpersonal Relations , Male , Poverty Areas , Program Evaluation , Schools , Students/psychology
13.
Australas Radiol ; 51(2): 190-5, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17419870

ABSTRACT

Emergency transcatheter embolization is a well-recognized measure to manage patients with life-threatening haemoperitoneum due to spontaneous ruptured hepatocellular carcinoma. Traditional embolization technique is to embolize the proper hepatic artery or the segmental hepatic artery by femoral approach using gelfoam pledgets. From 1997 to 2004, in 19 out of 96 embolizations, the embolization technique had to be modified because of tortuous conventional or aberrant hepatic vascular anatomy or parasitic supply to achieve successful embolization.


Subject(s)
Carcinoma, Hepatocellular/therapy , Embolization, Therapeutic/methods , Liver Neoplasms/therapy , Liver/blood supply , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/pathology , Emergencies , Female , Hepatic Artery/abnormalities , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Rupture, Spontaneous/therapy , Treatment Outcome
14.
Eur J Vasc Endovasc Surg ; 30(2): 133-6, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15886030

ABSTRACT

We report 13 successful emergency embolisations for 12 pseudoaneurysms performed in 10 patients. For five pseudoaneurysms the embolisation technique was modified according to number of supplying vessels, flow rate of pseudoaneurysms, vascular anatomy and whether there was clinical evidence of re-bleeding or not. Apart from traditional embolisation technique, modified embolisation techniques are also useful for endovascular therapy of pseudoaneurysms.


Subject(s)
Aneurysm, False/therapy , Aneurysm, Ruptured/therapy , Catheterization, Peripheral , Embolization, Therapeutic/methods , Viscera/blood supply , Adult , Aged , Aneurysm, False/diagnostic imaging , Aneurysm, Ruptured/diagnostic imaging , Emergency Service, Hospital , Female , Humans , Male , Middle Aged , Radiography , Treatment Outcome , Viscera/diagnostic imaging
15.
Australas Radiol ; 48(1): 14-6, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15027914

ABSTRACT

To audit the accuracy of magnetic resonance (MR) staging of nasopharyngeal carcinoma (NPC) in daily reporting, the MR images of 101 adult patients with newly diagnosed NPC reported between December 1996 and February 2002 were reviewed retrospectively. Based on the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) TNM staging criteria (1997), the tumour staging obtained from the MR reports and the MR films was compared by two experienced head and neck radiologists. The number of patients being upstaged, downstaged or unchanged was noted. In all stages, the NPC staging obtained from the MR reports revealed 18 (17.8%) understaged, eight (7.9%) overstaged and 75 (74.2%) the same stage when compared to the staging obtained from the MR films based on the AJCC/UICC criteria. The percentage of patients being understaged or overstaged, in decreasing order of frequency, were stages II, III, IV and I. Magnetic resonance of NPC should be reported by radiologists who are not only familiar with the pathology of this condition and its pattern of spread but who should also base their reports on the AICC/UICC staging criteria. The necessity to improve our MR staging accuracy is largely because it determines the type of therapy to be given and this has to be appropriate and adequate for a successful treatment.


Subject(s)
Carcinoma/diagnosis , Magnetic Resonance Imaging , Nasopharyngeal Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Carcinoma/pathology , Female , Humans , Male , Middle Aged , Nasopharyngeal Neoplasms/pathology , Neoplasm Staging
16.
Ann Acad Med Singap ; 31(1): 107-10, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11885484

ABSTRACT

INTRODUCTION: Renal artery pseudoaneurysms may arise as a complication of percutaneous nephrolithotomy (PCNL). Prompt recognition and treatment is essential to arrest haemorrhage which may be life threatening. CLINICAL PICTURE: A patient with chronic aortic dissection and malrotated right kidney underwent PCNL for right renal calculus. He developed delayed gross haematuria. TREATMENT: Angiography showed a pseudoaneurysm arising from one of two right renal arteries, which in turn arose from the false lumen of the aortic dissection. The supplying artery was successfully embolised. CONCLUSION: Renal artery pseudoaneurysms can be successfully treated with prompt angiography and embolisation, even in the presence of renal malrotation and aortic dissection.


Subject(s)
Aneurysm, False/diagnosis , Aneurysm, False/therapy , Aortic Dissection/diagnosis , Aortic Dissection/therapy , Embolization, Therapeutic/methods , Kidney Calculi/diagnosis , Kidney Calculi/therapy , Kidney/abnormalities , Renal Artery , Adult , Aortic Dissection/complications , Aneurysm, False/complications , Angiography , Chronic Disease , Follow-Up Studies , Humans , Kidney Calculi/complications , Laparoscopy/adverse effects , Laparoscopy/methods , Lithotripsy/methods , Male , Tomography, X-Ray Computed , Treatment Outcome , Ultrasonography, Doppler
17.
J Med Chem ; 44(23): 3759-63, 2001 Nov 08.
Article in English | MEDLINE | ID: mdl-11689062

ABSTRACT

A hypothetical pharmacophore of 5 alpha-reductase inhibitors was generated and served as a template in virtual screening. When the pharmacophore was used, eight isoflavone derivatives were characterized as novel potential nonsteroidal inhibitors of rat 5 alpha-reductase. This investigation has demonstrated a practical approach toward the development of lead compounds through a hypothetic pharmacophore via three-dimensional database searching.


Subject(s)
5-alpha Reductase Inhibitors , Enzyme Inhibitors/chemistry , Isoflavones/chemistry , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/chemistry , Animals , Binding Sites , Databases, Factual , Enzyme Inhibitors/pharmacology , In Vitro Techniques , Isoflavones/pharmacology , Microsomes, Liver/drug effects , Microsomes, Liver/enzymology , Models, Molecular , Rats , Structure-Activity Relationship
18.
Anticancer Drugs ; 12(3): 267-73, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11290874

ABSTRACT

Etoposide, an anti-neoplastic agent and a substrate of P-glycoprotein (P-gp), exhibits variable oral bioavailability. P-gp, the multidrug resistance gene (mdr1) product, has been considered as an absorption barrier against intestinal drug absorption. Terfenadine, an antihistamine, has been shown to be a P-gp inhibitor. The current study was designed to assess the effect of hydroxyzine, an antihistamine, on the transport of etoposide in the small intestine. Everted rat gut sacs were used to determine the absorption and exsorption of etoposide under different conditions, as rhodamine 123 was chosen to evaluate the role of P-gp in the drug interaction. The results showed that the transport of etoposide was significantly increased from the luminal site to the serosal site in the jejunum by 2- and 4-fold after 90 min in the presence of hydroxyzine and quinidine, respectively. A similar trend was observed in the ileal sacs. This in vitro exsorption study also demonstrated that hydroxyzine could reduce the efflux of etoposide to the luminal site in either jejunum or ileum. The effect of hydroxyzine on the pharmacokinetics of etoposide differed by the in vivo route of administration, thus assuming clinical importance for chemotherapeutic treatment.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Antineoplastic Agents, Phytogenic/pharmacokinetics , Etoposide/pharmacokinetics , Histamine H1 Antagonists/pharmacology , Hydroxyzine/pharmacology , Intestinal Absorption/drug effects , Intestine, Small/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Animals , Biological Availability , Chromatography, High Pressure Liquid , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Resistance, Multiple , In Vitro Techniques , Infusions, Intravenous , Jejunum/metabolism , Male , Microvilli/metabolism , Quinidine/pharmacology , Rats , Rats, Sprague-Dawley , Time Factors
19.
Neural Comput ; 11(4): 965-76, 1999 May 15.
Article in English | MEDLINE | ID: mdl-10226192

ABSTRACT

Pruning a neural network to a reasonable smaller size, and if possible to give a better generalization, has long been investigated. Conventionally the common technique of pruning is based on considering error sensitivity measure, and the nature of the problem being solved is usually stationary. In this article, we present an adaptive pruning algorithm for use in a nonstationary environment. The idea relies on the use of the extended Kalman filter (EKF) training method. Since EKF is a recursive Bayesian algorithm, we define a weight-importance measure in term of the sensitivity of a posteriori probability. Making use of this new measure and the adaptive nature of EKF, we devise an adaptive pruning algorithm called adaptive Bayesian pruning. Simulation results indicate that in a noisy nonstationary environment, the proposed pruning algorithm is able to remove network redundancy adaptively and yet preserve the same generalization ability.


Subject(s)
Bayes Theorem , Learning , Neural Networks, Computer , Brain Damage, Chronic , Filtration , Normal Distribution , Time Factors
20.
IEEE Trans Neural Netw ; 10(1): 64-71, 1999.
Article in English | MEDLINE | ID: mdl-18252504

ABSTRACT

Recently we have proposed a simple circuit of winner-take-all (WTA) neural network. Assuming no external input, we have derived an analytic equation for its network response time. In this paper, we further analyze the network response time for a class of winner-take-all circuits involving self-decay and show that the network response time of such a class of WTA is the same as that of the simple WTA model.

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