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Biomedical subjects

T Lee

Publications and source records attributed to T Lee.

At least 91 records · Page 5Linked to original sources
PubMed2000

Laparoscopic hepatic surgery guided by hookwire localization.

Due to recent improvements in radiographic technique, computed tomography (CT) occasionally delineates small hepatocellular carcinomas (HCCs) that are invisible with sonography. However, surgery has not been a viable option for these lesions because of the absence of tumor localization. We describe a new technique of preoperative tumor localization using a hookwire to guide laparoscopic surgery for such HCCs. A 68-year-old man with HCC had tumor recurrence after chemoembolization. Two recurrent lesions, 10 mm or less in diameter, located in segment III were demonstrated; not by sonography but by Lipiodol CT. We successfully placed a hookwire into the tumor through a 21-gauge needle under the guidance of CT. The hookwire instrument provided the only clue of tumor location at laparoscopy. The liver around the hookwire was thoroughly coagulated. The postoperative course was uneventful, and the tumor was completely ablated. Preoperative CT-guided hookwire placement is useful to localize and to laparoscopically treat small hepatic lesions.

Aged↗
PubMed2000

Structural studies of FIV and HIV-1 proteases complexed with an efficient inhibitor of FIV protease.

Three forms of feline immunodeficiency virus protease (FIV PR), the wild type (wt) and two single point mutants, V59I and Q99V, as well as human immunodeficiency virus type 1 protease (HIV-1 PR), were cocrystallized with the C2-symmetric inhibitor, TL-3. The mutants of FIV PR were designed to replace residues involved in enzyme-ligand interactions by the corresponding HIV-1 PR residues at the structurally equivalent position. TL-3 shows decreased (improved) inhibition constants with these FIV PR mutants relative to wt FIV PR. Despite similar modes of binding of the inhibitor to all PRs (from P3 to P3'), small differences are evident in the conformation of the Phe side chains of TL-3 at the P1 and P1' positions in the complexes with the mutated FIV PRs. The differences mimick the observed binding of TL-3 in HIV-1 PR and correlate with a significant improvement in the inhibition constants of TL-3 with the two mutant FIV PRs. Large differences between the HIV-1 and FIV PR complexes are evident in the binding modes of the carboxybenzyl groups of TL-3 at P4 and P4'. In HIV-1 PR:TL-3, these groups bind over the flap region, whereas in the FIV PR complexes, the rings are located along the major axis of the active site. A significant difference in the location of the flaps in this region of the HIV-1 and FIV PRs correlates with the observed conformational changes in the binding mode of the peptidomimetic inhibitor at the P4 and P4' positions. These findings provide a structural explanation of the observed Ki values for TL-3 with the different PRs and will further assist in the development of improved inhibitors.

Animals↗
PubMed2000

Efficacy and safety of preoperative lobar or segmental ablation via transarterial administration of ethiodol and ethanol mixture for treatment of hepatocellular carcinoma: clinical study.

Transarterial embolization (TAE) using various thrombotic substances for unresectable hepatocellular carcinoma (HCC) performed on many patients has resulted in a better survival rate. We evaluated the efficacy and clinical safety of using an Ethiodol-ethanol mixture as the embolizer for treatment of HCC and the possibility of a surgical approach for inoperable tumors after TAE. Twenty patients with HCC who underwent TAE and tumor resection were included in the study. Initially, eight had increased retention rate of indocyanine green dye via intravenous injection (0.5 mg/kg) at 15 minutes (ICGR15), and six had an insufficient residual volume that precluded them from undergoing tumor resection. TAE was performed by slowly infusing the mixture of Ethiodol and ethanol into the artery supplying the tumor until dual hepatic artery and portal vein embolization was achieved. Serum levels of alanine aminotransferase increased after embolization, but all biochemistry studies reverted to normal within 2 weeks. A decreased tumor size (n = 15), improved ICG (n = 8), and increased volume of the nonembolized lobe (n = 10) were noted. The operations performed were right lobectomy (n = 11), extended right lobectomy (n = 3), left lobectomy (n = 2), extended left lobectomy (n = 2), and wedge resection (n = 2), which included patients who did not want to undergo major hepatectomy. Complete tumor necrosis was found in seven cases. All patients survived with no associated complications. The 1-year survival rate was 95%. Transarterial Ethiodol and ethanol administration creating dual hepatic artery and portal vein embolization was a safe and efficacious method for treating HCC. It effectively decreases tumor size, causes compensatory hepatic hypertrophy, and improves the ICGR15, which allows a wider range of patients to undergo liver surgery and achieve better survival.

Adult↗
PubMed2000

Measurement of sirolimus in whole blood using high-performance liquid chromatography with ultraviolet detection.

BACKGROUND: Sirolimus, a potent immunosuppressive drug, exhibits intrapatient and interpatient variability of absorption and metabolism. Thus, therapeutic drug monitoring is important. OBJECTIVE: This paper describes a reverse-phase high-performance liquid chromatography (HPLC) method, using ultraviolet (UV) absorption for detection, for measuring sirolimus levels in human whole-blood samples. METHODS: The stability of sirolimus in whole blood was assessed under conditions likely to be encountered during transport of study samples to a central laboratory. The performance of the HPLC-UV assay in measuring sirolimus was compared with that of 3 established, validated HPLC assays with tandem mass-spectrometric (MS/MS) detection. Results of the HPLC-UV assay also were compared with results produced by a prototype microparticle enzyme immunoassay (MEIA). RESULTS: Inaccuracy for 3 in-house control samples was < or =4%, whereas within-assay repeatability (coefficient of variation [CV]) was < or =5% and between-assay reproducibility was < or =6.6%. Mean recovery of sirolimus from blood was 81.5%+/-4.3%. The lower limit of quantification was set at 6.5 ng/mL, and the repeatability CV at this concentration was 4.2% (n = 6). Sirolimus-containing whole-blood samples were stable for 3 freeze/thaw cycles when stored at -20 degrees C and for > or =2 days when stored at ambient temperature. The sample extract was shown to be stable for up to 54 hours at ambient temperature (approximately 22 degrees C) after extraction. Results of the HPLC-UV assay were consistent with those of the HPLC/ MS/MS assays but lower than those produced by MEIA. CONCLUSION: This HPLC-UV method is considered suitable for therapeutic drug monitoring of sirolimus.

Calibration↗
PubMed2000

An immunoassay for the measurement of sirolimus.

OBJECTIVE: This study assessed the performance characteristics of a new microparticle enzyme immunoassay (MEIA) for the determination of sirolimus in whole blood. BACKGROUND: In clinical investigatory studies, dose adjustments of the immunosuppressive drug sirolimus have been carried out using either high-performance liquid chromatography (HPLC) or, more recently, this investigational immunoassay kit based on the MEIA technique. METHODS: Calibration was made over the linear range 0 to 30 ng/mL. Inaccuracy and imprecision were assessed by means of 3 control samples supplied with the kit (5, 11, and 22 ng/mL) and dilution of an above-quantitation-limit sample (154 ng/mL). Specificity was determined by the addition of 2 sirolimus metabolites to sirolimus-free human whole blood or to I of the control samples supplied with the kit. In addition, whole-blood samples from patients receiving either cyclosporine or tacrolimus (N = 24) were analyzed for sirolimus. A comparison of the MEIA and a validated HPLC/MS/MS assay analyzed both pooled samples from patients receiving sirolimus and spiked samples (sirolimus 2-60 ng/mL). In a more extensive comparison of patient samples measured by the MEIA assay, a validated HPLC assay with UV detection (HPLC-UV) was used (HPLC-UV sirolimus 7-64 ng/mL). RESULTS: Inaccuracy (between-run) was < or =16.2% at all 4 concentrations (N = 5). Within-assay imprecision (repeatability) was <6% (N = 5), and between-assay imprecision (reproducibility) for the same samples was < 11% (N = 5). Recovery, assessed by means of 3 in-house control samples prepared in both fresh and previously frozen sirolimus-free human whole blood, ranged from 93.9% to 109.5%. The limit of detection, determined by dilution of the lowest nonzero calibrator (3 ng/mL), was set at 1 ng/mL, at which repeatability was 20.5% (N = 5). Five ng/mL of hydroxysirolimus cross-reacted with the assay by a mean of between 44% and 50% (N = 4); 5 ng/mL of 41-O-demethylsirolimus cross-reacted with the assay by a mean of between 86% and 127% (N = 4). Assay specificity was further challenged by ethylenediamine-tetraacetic acid (EDTA)-whole-blood samples from transplant patients not receiving sirolimus. These samples had tacrolimus and cyclosporine concentrations of 7.8 to 15.9 ng/mL and 38 to 485 microg/L, respectively. The median result was 0 ng/mL (third quartile, 0.7 ng/mL; maximum, 1.4 ng/mL); no value was above the lowest nonzero calibrator. The results of the comparison between the MEIA and the HPLC/MS/MS assay showed mean positive biases of 21% and 8% for the MEIA in measuring sirolimus in pooled patient samples and spiked samples, respectively. The results of the comparison of the MEIA and HPLC-UV median sirolimus concentrations were 18.2 and 20.1. Whole-blood samples anticoagulated with EDTA and containing sirolimus were stable for analysis by MEIA for 3 freeze-thaw cycles when stored at -20 degrees C and for 10 days when stored at 4 degrees C or at ambient temperature. A decline in sirolimus concentration occurred when samples were stored at 37 degrees C. CONCLUSION: The MEIA showed suitable precision across a clinically relevant concentration range. In terms of patient management, the practical significance of cross-reactivity with sirolimus metabolites remains to be assessed.

Antibody Specificity↗
PubMed2000

Cell-autonomous requirement of the USP/EcR-B ecdysone receptor for mushroom body neuronal remodeling in Drosophila.

Neuronal process remodeling occurs widely in the construction of both invertebrate and vertebrate nervous systems. During Drosophila metamorphosis, gamma neurons of the mushroom bodies (MBs), the center for olfactory learning in insects, undergo pruning of larval-specific dendrites and axons followed by outgrowth of adult-specific processes. To elucidate the underlying molecular mechanisms, we conducted a genetic mosaic screen and identified one ultraspiracle (usp) allele defective in larval process pruning. Consistent with the notion that USP forms a heterodimer with the ecdysone receptor (EcR), we found that the EcR-B1 isoform is specifically expressed in the MB gamma neurons, and is required for the pruning of larval processes. Surprisingly, most identified primary EcR/USP targets are dispensable for MB neuronal remodeling. Our study demonstrates cell-autonomous roles for EcR/USP in controlling neuronal remodeling, potentially through novel downstream targets.

Alleles↗
PubMed2000

Essential roles of Drosophila RhoA in the regulation of neuroblast proliferation and dendritic but not axonal morphogenesis.

The pleiotropic functions of small GTPase Rho present a challenge to its genetic analysis in multicellular organisms. We report here the use of the MARCM (mosaic analysis with a repressible cell marker) system to analyze the function of RhoA in the developing Drosophila brain. Clones of cells homozygous for null RhoA mutations were specifically labeled in the mushroom body (MB) neurons of mosaic brains. We found that RhoA is required for neuroblast (Nb) proliferation but not for neuronal survival. Surprisingly, RhoA is not required for MB neurons to establish normal axon projections. However, neurons lacking RhoA overextend their dendrites, and expression of activated RhoA causes a reduction of dendritic complexity. Thus, RhoA is an important regulator of dendritic morphogenesis, while distinct mechanisms are used for axonal morphogenesis.

Animal Structures↗
PubMed2000

Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models.

A historical perspective on the application of molecular dynamics (MD) to biological macromolecules is presented. Recent developments combining state-of-the-art force fields with continuum solvation calculations have allowed us to reach the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynamics trajectories. We illustrate such applications on nucleic acid duplexes, RNA hairpins, protein folding trajectories, and protein-ligand, protein-protein, and protein-nucleic acid interactions.

Base Sequence↗
PubMed2000

Image analysis of insulation mineral fibres.

We present two methods for measuring the diameter and length of man-made vitreous fibres based on the automated image analysis of scanning electron microscopy images. The fibres we want to measure are used in materials such as glass wool, which in turn are used for thermal and acoustic insulation. The measurement of the diameters and lengths of these fibres is used by the glass wool industry for quality control purposes. To obtain reliable quality estimators, the measurement of several hundred images is necessary. These measurements are usually obtained manually by operators. Manual measurements, although reliable when performed by skilled operators, are slow due to the need for the operators to rest often to retain their ability to spot faint fibres on noisy backgrounds. Moreover, the task of measuring thousands of fibres every day, even with the help of semi-automated image analysis systems, is dull and repetitive. The need for an automated procedure which could replace manual measurements is quite real. For each of the two methods that we propose to accomplish this task, we present the sample preparation, the microscope setting and the image analysis algorithms used for the segmentation of the fibres and for their measurement. We also show how a statistical analysis of the results can alleviate most measurement biases, and how we can estimate the true distribution of fibre lengths by diameter class by measuring only the lengths of the fibres visible in the field of view.

Journal Article↗
PubMed2000

Pharmacokinetics of mycophenolate mofetil in patients with end-stage renal failure.

BACKGROUND: Mycophenolate mofetil (MMF) acts as a prodrug for the immunosuppressive drug mycophenolic acid (MPA). It is rapidly converted to MPA following oral ingestion. MPA is metabolized to MPA glucuronide (MPAG), which is renally excreted. This study examines the pharmacokinetics of MPA and MPAG in patients with end-stage renal failure who were on hemodialysis (N = 10) or peritoneal dialysis (N = 10) treatment. METHODS: After an overnight fast, a single oral dose of 1 g MMF was given. Plasma concentrations of MPA and MPAG were measured from 0 (predose) to 36 hours after administration, using high-performance liquid chromatography (HPLC). The area under the concentration time curve (AUC) from 0 to 36 hours was calculated using the trapezoidal rule. RESULTS: Mean (+/- SD) AUC for MPA was 55.7 +/- 32.6 mg/L.h for hemodialysis patients and 44.7 +/- 14.7 mg/L.h for peritoneal dialysis patients, which is similar to expected values for subjects with normal renal function. The mean (+/- SD) maximum plasma concentration (Cmax) for MPA was lower than would be expected for subjects with normal renal function (16.01 +/- 10.61 mg/L for hemodialysis, 11.48 +/- 4.98 mg/L for peritoneal dialysis). MPAG clearance was prolonged with AUC approximately five times what would be expected in subjects with normal renal function (1565 +/- 596 mg/L.h for hemodialysis, 1386 +/- 410 mg/L.h for peritoneal dialysis). There was no significant difference for any of the pharmacokinetic parameters between subjects on hemodialysis and those on peritoneal dialysis. Plasma concentrations of MPA and MPAG did not fall significantly during hemodialysis. No MPA was detectable in hemodialysis or peritoneal dialysis fluid, but small amounts of MPAG were detected in hemodialysis fluid in 1 out of 10 subjects and in peritoneal dialysis fluid in 3 out of 10 subjects. CONCLUSIONS: The accumulation of MPAG may be responsible for the poor gastrointestinal tolerance of this drug in dialysis patients and probably limits the maximum dose of MMF that can be tolerated.

Adult↗
PubMed2000

Immune response to blood transfusion invery-low-birthweight infants.

BACKGROUND: Allogeneic blood transfusion is common in the treatment of neonatal anemia of prematurity or anemia due to multiple phlebotomies. The immune response of neonates to passenger leukocytes from allogeneic red cells was investigated. STUDY DESIGN AND METHODS: Fourteen infants (4 male, 10 female) prospectively were randomly assigned to receive either white cell-reduced (Group 1) or non-white-cell reduced (Group 2) irradiated blood. Blood samples were taken before and at various time intervals after transfusion (Days 1, 5-7,and 10-14). Cord blood from 11 healthy term infants was used for comparison. The following surface markers were used to assess immune modulation by flow cytometry: CD45RA/CD45RO, CD4/CD8, CD25/CD28, CD3/DR, CD14/B7, and CD3/CD56+CD16. Donor cell microchimerism was studied using semi-quantitative polymerase chain reaction Y-chromosome detection in female infants who received male donor blood. Donor and recipient HLA class II typing was performed with polymerase chain reaction with sequence specific primers. RESULTS: The lymphocyte counts in both groups were significantly increased after transfusion, and there was a significant increase in lymphocytes expressing CD45RA, CD3-/CD16+CD56, CD80, and CD3-/DR on Day 14. The premature infants' pretransfusion natural killer cell population (CD3-/CD16+CD56) was significantly lower than that of term infants, but it reached a similar level by Days 10-14. CD8 subpopulations were increased but not CD4+ cells. Two female infants (of 6) had circulating Y chromosomes 1 day after transfusion, and most of the infants effectively cleared the donor cells within 24 hours of transfusion. Two Group 2 infants who by chance received presumably HLA-haploidentical donor blood developed necrotizing enterocolitis. CONCLUSION: Blood transfusion alters immune cell antigen expression in premature neonates and may initially be immunostimulatory and later immunosuppressive.

Anemia, Neonatal↗
PubMed2000

Bacteriology and antimicrobial choice in hepatolithiasis.

BACKGROUND AND AIMS: Hepatolithiasis is prevalent in southeast Asia and presents a difficult management problem. Acute repeated episodes of cholangitis are frequently manifested in patients with hepatolithiasis. Without proper treatment, such infection can lead to liver abscess, secondary biliary cirrhosis, portal hypertension, and death from sepsis or hepatic failure. In addition to clearance of the stones and relief of bile stasis either by surgery or by interventional radiologic manipulation, effective antimicrobial therapy also plays a crucial role in the treatment of patients with hepatolithiasis. The aim of this study is to clarify the bacteriology in hepatolithiasis and to provide the information for an appropriate antimicrobial choice. METHODS: From July 1993 to June 1996, 150 patients with hepatolithiasis underwent surgical intervention. Bile specimens were routinely obtained by syringe aspiration from common bile duct. The syringe was immediately capped, and the bile was subsequently cultured for both aerobes and anaerobes. RESULTS: Bacteria were present in the bile of all patients. The bacteria most frequently found were gram-negative bacteria such as Klebsiella sp, Escherichia coli, and Pseudomonas sp, and the gram-positive Enterococcus sp. Bacteroides sp were the most frequently found anaerobes. CONCLUSIONS: This study demonstrated the close relationship between acute cholangitis in hepatolithiasis and enteric bacteria and also displayed the detailed antibiotic sensitivity results. Armed with this fruitful information, we believe the antibiotic treatment for acute cholangitis in hepatolithiasis should first aim at enteric bacteria and be adjusted later according to the results of bacteriologic cultures and clinical situation to achieve an effective microbial control.

Adult↗
PubMed2000

Neuropsychological functioning of adults with attention deficit hyperactivity disorder.

The neuropsychological functioning of adults with Attention Deficit Hyperactivity Disorder (ADHD) was compared to that of healthy controls and individuals with mild psychiatric disorders including attentional complaints. Thirty adults in each group were examined on the Conners' Continuous Performance Test (CPT) and measures of attention, executive function, psychomotor speed, and arithmetic skills. The ADHD group performed lower than healthy controls on most measures. However when compared to the psychiatric group, the performances of the ADHD group were not significantly lower on any of the measures. The predictive power of the tests was poor in discriminating ADHD from psychiatric disorder. Implications for the clinical diagnosis of ADHD are discussed.

Adolescent↗
PubMed2000

Analysis of patient profile in predicting home care resource utilization and outcomes.

OBJECTIVES: The study identifies patient profile variables that explain variation in resource utilization and outcomes for home healthcare. BACKGROUND: The healthcare reform and the demand for quality patient care have increased the need to identify key patient characteristics that can predict the use of resources and outcomes; however, home healthcare industry currently lacks adequate information collection to reflect these needs. This study explored both the resource use and care outcomes for nursing administrators in monitoring quality, resource distribution, and reimbursement policy decision making. METHOD: The conceptual framework is based on Donabedian's quality care elements (structure, process, and outcome) and Nursing Minimum Data Set. This is a retrospective descriptive study design in which 244 patient records and data were obtained from a home healthcare agency located in Washington, DC. A series of stepwise and discriminant analyses was conducted for data analysis. RESULTS: The findings indicated that the total number of nursing diagnoses and two specific nursing diagnoses (alteration in mobility and knowledge deficit in i.v. therapy) were strong predictors of overall resource use. Prognosis proved to be the strongest predictor of discharge outcomes. CONCLUSIONS/IMPLICATIONS: The results indicated that data related to nursing diagnoses and nursing interventions can provide valuable information in predicting resource use. Prognosis made by nursing judgment was also sensitive in predicting patient outcomes. These critical data elements should be included in describing home health patient characteristics and related resource utilization and care outcomes.

Adult↗
PubMed2000

Differences in health values among patients, family members, and providers for outcomes in schizophrenia.

OBJECTIVE: The objectives of this study were to determine whether there are important differences in how patients, family members, and health care providers (HCPs) value health outcomes in schizophrenia and to assess the degree to which such differences, if they exist, could adversely affect clinical and policy decision making. METHODS: Participants viewed videotaped depictions of simulated patients with mild and moderate symptoms of schizophrenia, with and without a common adverse drug effect (pseudoparkinsonism), and then provided standard gamble and visual analog scale ratings of desirability of these states. SUBJECTS: A convenience sample of unrelated patients (n = 148), family members of patients (n = 91), and HCPs (nurses, psychologists, doctors of pharmacy, and doctors of medicine; n = 99) was drawn from geographically and clinically diverse environments. RESULTS: Patients' and family members' utilities for health states averaged 0.1 to 0.15 units higher than those of HCPs (P <0.002 for differences between groups, ANOVA for multiple observations). The disutility of adverse drug effects was less for health professionals than patients and family members (P = 0.008). Health professionals tended to prefer states with mild symptoms with extrapyramidal side effects to states with moderate symptoms. Patients and family members found these states equally preferable (P <0.007 for differences between groups). CONCLUSIONS: There are systematic differences in values for health outcomes between patients and HCPs with regard to states with adverse effects of antipsychotic drugs. Family members of patients in general had values that were more similar to those of patients than were those of health professionals. The results emphasize the importance of participation by patients (or family member proxies) in clinical decision making and guideline development.

Adult↗