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Biomedical subjects

E Wong

Publications and source records attributed to E Wong.

At least 109 records · Page 6Linked to original sources

Mass spectrometric analysis of arachidonyl-containing phospholipids in human U937 cells.

The human histiocytic lymphoma U937 cell line contains a rich source of the 85 kDa cytosolic phospholipase A2 (cPLA2). DMSO-differentiated U937 cells were used as a model to investigate the free arachidonic acid release, the arachidonate distribution and the phospholipid source of arachidonate upon Ca2+ ionophore stimulation. A combination of several chromatographic and mass spectrometric techniques was employed in this study. The amount of free arachidonic acid (AA) released upon stimulation, the arachidonate content in total lipids and in each of the phospholipid classes were determined by gas chromatography/mass spectrometry (GC/MS). Glycerophosphoethanolamine (GPE) was found to be the major pool of arachidonate in differentiated human U937 cells (55%) and glycerophosphocholine (GPC) and glycerophosphoinositol (GPI) contributed 22 and 8%, respectively. Upon Ca2+ ionophore stimulation, GPE class lost the largest amount of arachidonate, followed by GPC class. GPI class, however, gained a substantial amount of arachidonate. Most of the arachidonate depleted from GPE and GPC was recovered as free AA, some of which was rapidly esterified into GPI species. GC/MS with electron capture negative chemical ionization provided excellent sensitivity for the measurement of arachidonic acid which was derivatized to its pentafluorobenzyl ester. Intact phospholipid molecular species including the arachidonyl-containing phospholipid species were identified using capillary high-performance liquid chromatography/continuous-flow liquid secondary ion mass spectrometry (CF-LSIMS). No specificity was found for releasing free AA among the arachidonyl-containing GPE and GPC species upon Ca2+ ionophore stimulation. CF-LSIMS provided a sensitive and effective means of detecting intact phospholipid species.

Arachidonic Acid↗

Control of lymphocyte development by the Ikaros gene family.

Lymphoid cell differentiation relies on precisely orchestrated gene activation and repression events. Gene targeting studies have demonstrated crucial roles for the transcription factors Ikaros and Aiolos in regulating multiple stages of B and T cell development. Recent experiments suggest that Ikaros and Aiolos set B cell antigen-receptor (BCR)- and TCR-mediated signaling thresholds and that the molecules exist within T cells in nuclear complexes that contain nucleosome remodeling and histone deacetylase activities.

Animals↗

Pharmacokinetics of bambuterol during oral administration to asthmatic children.

AIMS: To investigate dose proportionality, dosing frequency, and ethnic aspects of the pharmacokinetics of bambuterol in asthmatic children, and to discuss the relationship with previous observations in adults. METHODS: Forty-eight children in four different studies completed two double-blind bambuterol treatments each (daily doses of bambuterol hydrochloride): 12 preschool (5 mg x 2 vs 10 mg) and 12 school (10 mg vs 20 mg) Caucasians, 12 preschool (2.5 mg vs 5 mg), and 12 school (10 mg vs 20 mg) Orientals. Peak plasma concentrations and dosing interval area under curve (AUC) of bambuterol and the active metabolite terbutaline were assessed at steady state. Treatment differences were analysed statistically within each study. Differences between the studies and the relation to steady-state AUC in adults were described. RESULTS: Dose proportionality was seen for terbutaline but not for bambuterol. Twice-daily dosing (2 x AUC(0,12 h)) could not be shown to differ from once-daily dosing (AUC(0,24 h)) in the preschool Caucasians. Mean AUC of terbutaline was 128 and 242 nmol l-1 h in the preschool Caucasians (5 mg/12 h; 10 mg/24 h), 213 and 406 nmol l-1 h in the Caucasian school children (10 mg; 20 mg), 87.4 and 202 nmol l-1 h in the Oriental preschool children (2.5 mg; 5 mg), and 356 and 640 nmol l-1 h in the Oriental school children (10 mg; 20 mg). Oriental school children had higher plasma concentrations of bambuterol and terbutaline than Caucasian school children. The strict ethnic implication of the difference could not be elucidated, because demographic data were not perfectly matched. Terbutaline AUC was only moderately increased in the Caucasian school children compared with Caucasian adults. The increase was more pronounced in Oriental children and in some preschool Caucasians. The highest concentration of terbutaline, 58 nmol l-1, was seen in an Oriental school child after a 20 mg dose. CONCLUSIONS: Caucasian school children can be given bambuterol hydrochloride very much as Caucasian adults, 10 or 20 mg once daily, but Oriental preschool and school children plus preschool Caucasians should be given lower doses.

Administration, Oral↗

A controlled trial of traditional Chinese herbal medicine in Chinese patients with recalcitrant atopic dermatitis.

BACKGROUND: There have been published reports from the United Kingdom of good responses to the use of traditional Chinese herbal medicine (Zemaphyte, Phytopharm Plc, Cambridge, UK) in treating recalcitrant atopic dermatitis. We conducted a double-blind, placebo-controlled, cross-over study among Chinese patients with recalcitrant atopic dermatitis using this same herbal preparation. METHODS: Forty patients were recruited. They were given Zemaphyte and placebo in random order, each for 8 consecutive weeks with a 4-week wash-out period in between. Scores based on the severity and extent of four clinical parameters (erythema, surface damage, lichenification and scaling) were recorded at baseline and at 4-weekly intervals throughout the 20-week trial period. RESULTS: Thirty-seven patients completed the trial. There was a general trend of clinical improvement with time throughout the trial period in both patient groups, irrespective of whether they received Zemaphyte or placebo first. Zemaphyte, however, offered no statistically significant treatment effect over placebo for all four clinical parameters, except for lichenification at week 4. There were no significant carry-over effects. Blood tests for hematologic, renal and liver functions were all normal throughout the trial. CONCLUSIONS: Zemaphyte did not seem to benefit Chinese patients with recalcitrant atopic dermatitis in our study. Further research is required to evaluate its efficacy.

Adolescent↗

Long-term outcome and functional health status following intensive care in Hong Kong.

OBJECTIVES: To assess mortality and functional health status of patients at 1 yr following admission to a multidisciplinary intensive care unit (ICU) in Hong Kong. To determine which factors are associated with a poor long-term outcome. DESIGN: Prospective data collection and review. SETTING: A 14-bed multidisciplinary ICU in a 1,400-bed tertiary care university hospital. PATIENTS: Data from 2,268 consecutive patients admitted over a 2.5-yr period was analyzed, including follow-up at 1 yr in 853 adult survivors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The patients' clinical details and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were recorded on day 2 of admission and reviewed at time of discharge or death. The mean APACHE II score on admission was 18. Survival status at 1 yr was ascertained and the sickness impact profile (SIP) scored as a measure of functional health status for survivors. Sixty-five percent of patients survived to discharge from hospital and 44% of patients were known to survive to 1 yr; 6% of patients could not be traced at 1 yr. Functional health status was assessed in 85% of eligible adult patients. Survivors to 1 yr were younger than nonsurvivors and had lower APACHE II scores. The median SIP score was 5.1, (25th and 75th percentiles: 0 to 15), and 76% of patients had SIP scores < or = 15, i.e., normal health to moderate disability. Five percent of the patients were not working or had retired for health-related reasons. Stepwise logistic regression to identify factors associated with poor functional health status defined as a SIP score >15 at 1 yr found increasing age, cardiac/ respiratory arrest, intracranial hemorrhage, and trauma to be associated with poor outcomes. A correlation was found between APACHE II scores and SIP scores (Spearman's correlation coefficient = 0.13, p < .001). CONCLUSIONS: The SIP scores indicated that the majority of patients who survived to 1 yr after ICU admission enjoyed reasonable functional health status. A poor functional health status at 1 yr did not relate to the severity of the acute illness suffered, but appeared to relate to the prognosis of the underlying disease process.

APACHE↗

Transthoracic needle aspiration biopsy for the diagnosis of localised pulmonary lesions: a meta-analysis.

BACKGROUND: Persisting controversy surrounds the use of transthoracic needle aspiration biopsy (TNAB) stemming from its uncertain diagnostic accuracy. A systematic review and meta-analysis was therefore conducted to evaluate the accuracy of TNAB for the diagnosis of solitary or multiple localised pulmonary lesions. METHODS: Searches for English literature papers in Index Medicus (1963-1965) and Medline (1966-1996) were performed and the bibliographies of the retrieved articles were systematically reviewed. Articles evaluating the accuracy of TNAB in series of consecutive patients presenting with solitary or multiple pulmonary lesions were considered. Only papers in which >/=90% of patients were given a final diagnosis according to an appropriate reference standard were included in the meta-analysis. RESULTS: A total of 48 studies were included and five meta-analyses were conducted according to four diagnostic thresholds. From the pooled sensitivity and specificity corresponding to each diagnostic threshold, associated likelihood ratios (LRs) were derived for malignant disease as follows: (1) malignant versus all other categories, LR = 72; (2) malignant or suspicious versus all others, LR = 49; (3) suspicious versus all categories but malignant, LR = 15; (4) benign versus all others, LR = 0.07; and (5) specific benign diagnosis versus all others, LR = 0.005. Differences in methodological quality of the studies, needle types, or whether a cytopathologist participated in the procedure failed to explain the heterogeneity of the results found in almost every meta-analysis. Given a 50% probability of malignancy prior to the TNAB, post-test probabilities of malignancy upon receiving the results would be malignant, 99%; suspicious, 94%; non-specific benign, 7%; and benign with a specific diagnosis, 0.6%. CONCLUSIONS: Given the intermediate pre-test probabilities that would probably lead to performing TNAB, findings of "malignant" or of a specific diagnosis of a benign condition provide definitive results. Findings of "suspicious" markedly increase the probability of malignancy, and "benign" markedly decreases it but may not be considered definitive.

Biopsy, Needle↗

Epidural catheter placement in the rabbit--a novel approach.

BACKGROUND: Using a pediatric epidural set and through caudal approach, we studied a relatively non-invasive technique for epidural percutaneous cannulation in rabbit for chronic laboratory investigations. METHODS: Ten rabbits weighing over 3 kg were chosen and anesthetized with intravenous pentothal. A #19 pediatric Touhy needle and 23-gauge catheter were used for cannulation. Via the caudal approach, the epidural space could be located either by a "give" or with a technique of loss of resistance. Under fluoroscopy the catheter was tested with the injection of contrast medium for the confirmation of the proper position. The catheter was then tunneled under the skin and secured. The rabbits were kept in standard care for 4 weeks and then sacrificed by intraperitoneal pentothal overdose. A pathologist blinded to the study carefully examined the whole spine by laminectomy from cervical to coccyx and the findings were recorded. RESULTS: With the injection of contrast medium, the final position of the catheter was validated by fluoroscopy in all rabbits. Two rabbits sustained immediate complications from the contrast medium and/or technique, of which one died shortly after the contrast medium injection and the other had weakness of the hind legs for a week. At sacrifice, all the catheters were found in good position. Two had hematoma associated with signs of trauma. One developed subcutaneous abscess. One had stitch infection of skin. CONCLUSIONS: Percutaneous cannulation of epidural catheter is possible in the rabbit. Complications could be ameliorated by prudent approach in a skillful hand. It can be a reasonable model for the study of centrally administered medicines and their neurotoxicity.

Animals↗

Pansteatitis in a free-ranging red-tailed hawk (Buteo jamaicensis).

A free-ranging juvenile female red-tailed hawk (Buteo jamaicensis) that was unable to fly was admitted to a rehabilitation center and died 1 day later. Hematology and serum chemistry abnormalities included moderate regenerative anemia, elevated creatine kinase, and hyperphosphatemia. Necropsy revealed a generalized steatitis, and histology showed a necrotizing and granulomatous pansteatitis with intralesional pigment compatible with ceroid. There was also moderate diffuse myodegeneration, mild multifocal cardiomyopathy, and mild multifocal hepatic necrosis. These changes and lesions resemble those caused by vitamin E deficiency in mammals and fish-eating birds.

Adipose Tissue↗

2-Pyridinyl-3-(4-methylsulfonyl)phenylpyridines: selective and orally active cyclooxygenase-2 inhibitors.

A series of novel 2-pyridinyl-3-(4-methylsulfonyl)phenylpyridines has been synthesized and evaluated with respect to their ability to inhibit the isozymes of cyclooxygenase, COX-1, and COX-2. Optimum COX-2 activity is observed by introduction of a substituent at C5 of the central pyridine. 5- Chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine 33 was identified as the optimum compound in this series.

Administration, Oral↗

Cooperative folding of a protein mini domain: the peripheral subunit-binding domain of the pyruvate dehydrogenase multienzyme complex.

The peripheral subunit-binding domain from the dihydrolipoamide acetyltransferase (E2) component of the pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus is stably folded, despite its short sequence of only 43 amino acid residues. A 41 residue peptide derived from this domain, psbd41, undergoes a cooperative thermal unfolding transition with a tm of 54 degrees C. This three-helix protein is monomeric as judged by ultracentrifugation and concentration-dependent CD measurements. Peptides corresponding to the individual helices are largely unstructured both alone and in combination, indicating that the unusual stability of this protein does not arise solely from unusually stable alpha-helices. Chemical denaturation by guanidine hydrochloride is also cooperative with a delta GH2O of 3.1 kcal mol-1 at pH 8.0 and 25 degrees C. The chemical denaturation is broad with an m-value of 760 cal mol-1 M-1. psbd41 contains a buried aspartate residue at position 34 that may provide stability and specificity to the fold. A mutant peptide, psbd41Asn was synthesized in which the buried aspartate residue was mutated to asparagine. This peptide still folds cooperatively and it is monomeric, but is much less thermostable than the wild-type with a tm of only 31 degrees C. Chemical denaturations at 4 degrees C give an m-value of 740 cal mol-1 M-1, similar to the wild-type, but the stability delta GH2O is only 1.4 kcal mol-1. Both the wild-type and the mutant unfold at extremes of pH, but at 4 degrees C psbd41Asn is folded over a narrower pH range than the wild-type. Although the mutant unfolds cooperatively by thermal and by chemical denaturation, its NMR spectrum is significantly broader than that of the wild-type and it binds ANS. These results show that Asp34 is vital for the stability and specificity of this structure, the second smallest natural sequence known to fold in the absence of disulfide bonds or metal or ligand-binding sites.

Amino Acid Sequence↗

"Incomplete resection" in non-small cell lung cancer: need for a new definition. Canadian Lung Oncology Group.

BACKGROUND: This study was designed to determine the prognostic value of positive surgical resection margin or highest nodal station sampled at thoracotomy in patients with non-small cell lung cancer. METHODS: Two reviewers independently examined the surgical records and pathologic reports from a randomized trial comparing computed tomography versus mediastinoscopy for staging of lung cancer. They recorded pathologic findings at the surgical resection margin, the highest mediastinal nodal station sampled at thoracotomy, histologic type, tumor size, N status, and evidence of vascular or lymphatic invasion. These variables formed the independent variables in logistic regression models to predict recurrence. RESULTS: Except for 1 patient, follow-up at 3 years for 399 included patients was complete. Significant predictors of recurrence were tumor size (odds ratio [OR], 1.2 (per centimeter); 99% CI [confidence interval], 1.1 to 1.4), and N status (compared with N0, N1: OR, 1.6; CI, 0.8 to 3.1; N2: OR, 3.2; CI, 1.4 to 7.5). Other variables, including positive surgical resection margin, did not predict early recurrence or death. CONCLUSIONS: In patients with non-small cell lung cancer, surgical resection margin or highest nodal station sampled at thoracotomy that are involved by carcinoma do not predict recurrence. The current definition of incomplete resection has limited prognostic significance.

Aged↗

fMRI of monkey visual cortex.

While functional magnetic resonance imaging (fMRI) is now used widely for demonstrating neural activity-related signals associated with perceptual, motor, and cognitive processes in humans, to date this technique has not been developed for use with nonhuman primates. fMRI in monkeys offers a potentially valuable experimental approach for investigating brain function, which will complement and aid existing techniques such as electrophysiology and the behavioral analysis of the effects of brain lesions. There are, however, a number of significant technical challenges involved in using fMRI with monkeys. Here, we describe the procedures by which we have overcome these challenges to carry out successful fMRI experiments in an alert monkey, and we present the first evidence of activity-related fMRI signals from monkey cerebral cortex.

Animals↗

The effect of addition of calcipotriol ointment (50 micrograms/g) to acitretin therapy in psoriasis.

Our purpose was to find out whether the addition of calcipotriol ointment (50 micrograms/g) to systemic treatment with acitretin produces additional therapeutic effects and thereby an acitretin-sparing effect, and further to investigate the safety and tolerability of this combination. A multicentre, randomized, double-blind placebo-controlled study was designed. Patients were randomized to receive calcipotriol or placebo. All patients were treated with a starting dose of 20 mg acitretin per day and doses were adjusted at 2-weekly intervals with increments of 10 mg per day up to a maximum of 70 mg per day. The dose requirement for acitretin, clinical signs and adverse events were recorded. Seventy-six patients were randomized to treatment with calcipotriol 50 micrograms/g ointment twice daily and 59 patients to treatment with the vehicle only twice daily. Clearance or marked improvement was achieved by 67% of the patients in the calcipotriol group and by 41% of the patients in the placebo group (P = 0.006). Calcipotriol treatment proved to have a statistically significant additional effect to acitretin on the Psoriasis Area and Severity Index, redness, thickness and scaliness as compared with placebo. Clearance or marked improvement was achieved with a statistically significantly lower cumulative dose of acitretin by the patients in the calcipotriol group as compared with the placebo group. The number of patients reporting adverse events was pronounced and largely related to acitretin. No significant differences were observed between the two treatment groups with respect to adverse events. Laboratory assessments were essentially normal. The addition of calcipotriol ointment to acitretin treatment contributes to the efficacy, reduces the cumulative dose of acitretin to reach marked improvement or clearance, and is well-tolerated and safe.

Acitretin↗

Optimal preload adjustment of maximal ventricular power index varies with cardiac chamber size.

BACKGROUND: Maximal left ventricular power (PWRmax) can index contractile function and reserve; however, its marked preload dependence mandates load adjustment to yield a more cardiac-specific measurement. Prior studies have used varying methods, but supporting data have generally been lacking. We hypothesized that the optimal approach for preload adjustment varies with ventricular volume (particularly end-systolic volume) and is significantly different for dilated hearts with reduced left ventricular function compared with small to normal-sized hearts with normal systolic function. METHODS: Left ventricular pressure-volume relations were measured by the conductance catheter method in 36 patients, with preload altered by inferior vena cava obstruction. Patients with normal ventricles (n = 16), hypertrophy or mitral stenosis (n = 12), and dilated cardiomyopathy (n = 8) were divided into three groups based on resting end-diastolic volume: group 1, 66.3 +/- 12; group 2, 118.1 +/- 20; and group 3, 218.2 +/- 48 ml. PWRmax was the maximal product of simultaneous left ventricular pressure and rate of volume change. PWRmax end-diastolic volume (EDV) data were fit to a power function, PWRmax = alphaEDVbeta (where alpha is a scaling factor and beta is the power coefficient), and the preload sensitivity of beta and PWRmax/EDVbeta ratios (beta = 1, 2, or best fit) were compared. RESULTS: Beta varied directly with chamber size: 0 = 0.004 x (EDV + 0.56), r = 0.65, p < 0.0001. However, it was equally well approximated by 1.0 in groups 1 and 2 (ESV <75 ml, EF >40%), whereas beta = 2 was more appropriate in group 3. CONCLUSION: PWRmax/EDV provides adequate preload independence in all but dilated hearts with reduced LV function, whereas PWRmax/EDV2 is required in the latter. These data should help clinical application of a noninvasive PWRmax index for assessing chamber contractility and contractile reserve in human beings.

Adult↗

Physiological effects of resistant starches on fecal bulk, short chain fatty acids, blood lipids and glycemic index.

OBJECTIVE: To assess the effects on fecal bulking, fecal short chain fatty acid (SCFA) production, blood lipids and glycemic indices of two different forms of resistant starch (RS2 and RS3) from a high-amylose cornstarch. METHODS: Twenty-four healthy subjects (12 men; 12 women) consumed four supplements taken for 2 weeks in random order separated by 2-week washout periods. The supplements were a low-fiber (control) and supplements providing an additional 30 g dietary fiber as wheat bran (high-fiber control) or the equivalent amount of resistant starch analyzed gravimetrically as dietary fiber from RS2 or RS3. Four-day fecal collections and 12-hour breath gas collections were obtained at the end of each period. Fasting blood was taken at the beginning and end of each period. Glycemic indices of supplements were also assessed. RESULTS: The wheat bran supplement increased fecal bulk 96+/-14 g/day compared with the low-fiber control (p<0.001) with the mean for both resistant starches also being greater (22+/-8 g/day) than the low-fiber control (p=0.013). On the resistant starch phases, the mean fecal butyrate:SCFA ratio, which has been suggested to have positive implications for colonic health, was significantly above the low-fiber control by 31+/-14% (p=0.035). Resistant starches did not alter serum lipids, urea or breath H2 or CH4. No significant differences in glycemic index were seen between the RS and control supplements. CONCLUSION: The potential physiological benefits of the resistant starches studied appear to relate to colonic health in terms of effects on fecal bulk and SCFA metabolism.

Adult↗

Development of a questionnaire to measure quality of life in patients with irritable bowel syndrome.

OBJECTIVE: To develop a questionnaire for measuring health-related quality of life (HRQL) in patients with Irritable Bowel Syndrome (IBS). METHODS: We surveyed the existing literature, and interviewed patients and clinicians, to develop a list of 182 potential problems for IBS patients. One hundred patients with IBS completed a questionnaire in which they told us whether each of the 182 items was a problem for them, and if so the magnitude of their importance in their lives. RESULTS: Patients identified four major problem areas: bowel symptoms, fatigue, activity limitations, and emotional dysfunction. On the basis of these findings, we constructed a 26-item questionnaire which, in pre-testing, 16 patients found clear and easy to complete. CONCLUSION: We have developed a questionnaire that measures HRQL in IBS patients and is suitable for use as an outcome measure in clinical trials in IBS.

Activities of Daily Living↗

Effect of nimodipine on memory after cerebral infarction.

OBJECTIVES: Epidemiological studies indicate widespread memory impairment in patients with stroke in the early post-ictal stage. Nimodipine may have psychopharmacological properties and may improve memory. We conducted a single-blind randomized controlled trial to determine whether nimodipine given 7-14 days after cerebral infarction improved memory. MATERIAL AND METHODS: One hundred patients with acute cerebral infarction were consecutively enrolled between D7 to D14. After stratification, patients were randomized to receive oral nimodipine 90 mg daily for 12 weeks, or no drug. Independent assessors administered Mini-Mental State Examination (MMSE) and Fuld Object-Memory Evaluation (FOME) at baseline, 6 weeks, and 12 weeks. RESULTS: Patients receiving nimodipine showed greater improvement in FOME mean scores at 12 weeks (P=0.0334), and also in FOME score change across time (P=0.0283). Patients with severe disability who received nimodipine also showed greater MMSE score change across time (P=0.0495). CONCLUSION: Nimodipine given 7-14 days after cerebral infarction for 3 months results in memory improvement.

Aged↗