Utilization and monitoring of aminoglycosides in oncology patients at a Hong Kong government hospital.
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Aminoglycosides↗
Biomedical subjects
S Chang
Publications and source records attributed to S Chang.
Planetary environments and the origin of life.
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Evolution, Planetary↗
[Relationship between smoking and drinking and herniation of intervertebral disc].
To study whether there is relationship between smoking and drinking and herniation of intervertebral disc, we investigated 214 patients who had been proved with herniation of intervertebral disk during 1986-1996. The results were that in the younger (< or = 35 year old), no matter whether they drank or not, the number of smoker in the patients with herniation of intervertebral disc was more than that in the control group; no matter whether they smoked or not, the number of drinker in the patients with herniation of intervertebral disc was more than that in the control group.
Adolescent↗
[Dietary intake of some micronutrients in different provinces of China].
Based on the data collected in 1992 China National Nutrition Survey, which covered 100,201 persons of all ages in 29 provinces, the dietary intakes of some micronutrients were calculated. The intake of calcium, retinal equivalent and riboflavin were the most insufficient nutrients; zinc, selenium and thiamin were close to (80%-90%) of Chinese RDAs. The intakes of niacin, ascorbic acid and vitamin E were sufficient. The regions in the northeast, northwestern and the southeastern inland were more at risk of nutrition deficiency. Dietary intervention or food fortification with some micronutrients could be used for improving the situation.
Calcium↗
Analysis of a core domain in Drosophila DNA topoisomerase II. Targeting of an antitumor agent ICRF-159.
To investigate the biochemical properties of individual domains of eukaryotic topoisomerase (topo) II, two truncation mutants of Drosophila topo II were generated, ND406 and core domain. Both mutants lack the ATPase domain, corresponding to the N-terminal 406 amino acid residues in Drosophila protein. The core domain also lacks 240 amino acid residues of the hydrophilic C-terminal region. The mutant proteins have lost DNA strand passage activity while retaining the ability to cleave the DNA and the sequence preference in protein/DNA interaction. The cleavage experiments carried out in the presence of several topo II poisons suggest that the core domain is the key target for these drugs. We have used glass-fiber filter binding assay and CsCl density gradient ultracentrifugation to monitor the formation of a salt-stable, protein-clamp complex. Both truncation mutant proteins can form a clamp complex in the presence of an antitumor agent, ICRF-159, suggesting that the drug targets the core domain of the enzyme and promotes the intradimeric closure at the N-terminal interface of the core domain. Furthermore, the salt stability of the closed protein clamp induced by ICRF-159 depends on the presence and closure of the N-terminal ATPase domain.
Adenosine Triphosphatases↗
Structural requirements for outside-in and inside-out signaling by Drosophila neuroglian, a member of the L1 family of cell adhesion molecules.
Expression of the Drosophila cell adhesion molecule neuroglian in S2 cells leads to cell aggregation and the intracellular recruitment of ankyrin to cell contact sites. We localized the region of neuroglian that interacts with ankyrin and investigated the mechanism that limits this interaction to cell contact sites. Yeast two-hybrid analysis and expression of neuroglian deletion constructs in S2 cells identified a conserved 36-amino acid sequence that is required for ankyrin binding. Mutation of a conserved tyrosine residue within this region reduced ankyrin binding and extracellular adhesion. However, residual recruitment of ankyrin by this mutant neuroglian molecule was still limited to cell contacts, indicating that the lack of ankyrin binding at noncontact sites is not caused by tyrosine phosphorylation. A chimeric molecule, in which the extracellular domain of neuroglian was replaced with the corresponding domain from the adhesion molecule fasciclin II, also selectively recruited ankyrin to cell contacts. Thus, outside-in signaling by neuroglian in S2 cells depends on extracellular adhesion, but does not depend on any unique property of its extracellular domain. We propose that the recruitment of ankyrin to cell contact sites depends on a physical rearrangement of neuroglian in response to cell adhesion, and that ankyrin binding plays a reciprocal role in stabilizing the adhesive interaction.
Amino Acid Sequence↗
Immunogenicity of vector DNA vaccine constructs of pseudorabies virus immediate early gene (IE180) in mice and swine.
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Animals↗
Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992.
BACKGROUND: Little is known about the cause of inflammatory breast carcinoma (IBC), the most aggressive form of breast cancer. To the authors' knowledge, no studies have investigated whether IBC risk factors are different from those for breast carcinoma overall, and there has been only one report of IBC incidence and survival patterns. METHODS: The authors used data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute for the period 1975-1992 to calculate age-adjusted incidence and survival rates for 913 white and 121 African American women with IBC involving dermal invasion of lymphatic ducts and 166,375 white and 13,674 African American women with other types of breast carcinoma (non-IBC). RESULTS: Between 1975-1977 and 1990-1992, IBC incidence doubled, increasing among whites from 0.3 to 0.7 cases per 100,000 person-years and among African Americans from 0.6 to 1.1 cases. However, rates for African Americans varied due to the small numbers of IBC cases. The twofold increase in IBC incidence was higher than that observed for non-IBC during the same period (27% for African Americans and 25% for whites). IBC patients were significantly younger at diagnosis than non-IBC patients; and among both IBC and non-IBC patients, African Americans were younger than whites. Overall survival was significantly worse for IBC patients than for non-IBC patients and for African Americans than for whites. Among whites, 3-year survival improved more for IBC patients than for non-IBC patients between 1975-1979 and 1988-1992, increasing from 32% to 42% for IBC patients (P=0.0001) and from 80% to 85% for non-IBC patients (P=0.0001). CONCLUSIONS: The disparities observed in incidence trends and age at diagnosis, particularly according to race, highlight the need for further investigation of the differences between IBC and non-IBC incidence.
Adenocarcinoma↗
Identification of the basolateral targeting determinant of a peripheral membrane protein, MacMARCKS, in polarized cells.
BACKGROUND: Although the molecular determinants that specify the targeting of transmembrane proteins to the apical or basolateral membrane domains within polarized epithelial cells have been well characterized, very little is known about the targeting of peripheral membrane proteins within these cells. MacMARCKS is a member of the MARCKS family of protein kinase C (PKC) substrates. This myristoylated protein regulates actin structure at cell membranes and is essential for the morphogenic movement of neuroepithelial cells during the formation of the neural tube. RESULTS: MacMARCKS was specifically targeted to sites of cell-cell contact in the basolateral domain of polarized Madin-Darby canine kidney (MDCK) epithelial cells and was displaced from this location upon activation of PKC. We defined the basolateral targeting determinant of MacMARCKS to be the effector domain, a basic region spanning 24 amino acids and containing the PKC phosphorylation sites as well as binding sites for calmodulin and actin. This domain, in conjunction with a myristoyl moiety, was sufficient to target a non-membrane-associated protein--green fluorescent protein--specifically to the basolateral surface of polarized MDCK cells. CONCLUSIONS: This is the first description of a specific amino acid sequence that specifies targeting of a peripheral membrane protein to the basolateral membrane in polarized epithelial cells.
Animals↗
Identifying Lys359 as a critical residue for the ATP-dependent reactions of Drosophila DNA topoisomerase II.
Substituting Lys359 with either Gln or Glu in the highly conserved QTK-loop in the DNA gyrase B protein homologous domain of Drosophila topoisomerase II inactivates its catalytic activities. Although strand passage and DNA-dependent ATPase activities are affected in these mutant proteins, their DNA cleavage activity is comparable with the wild-type enzyme and can be stimulated to the same level by topoisomerase-targeting anticancer drugs. The sequence specificity in the DNA cleavage reaction remains unaltered for the mutant proteins. We have used both glass fiber filter binding assay and CsCl density gradient ultracentrifugation to monitor the formation of a salt-stable, protein-clamp complex. Both Gln and Glu mutant proteins can form a clamp complex in the presence of 5'-adenylyl-beta,gamma-imidodiphosphate, albeit with a lower efficiency than the wild-type enzyme. However, the mutant proteins can form a stable complex either in the presence of ATP or in the absence of any cofactors. These results are in an interesting contrast with the wild-type enzyme, which cannot form a stable complex under similar conditions. Our data suggest that Lys359 is critical for the catalytic activity of topoisomerase II and may have an important function in the ATP signaling process.
Adenosine Triphosphate↗
Transport and turnover of microtubules in frog neurons depend on the pattern of axonal growth.
The transport of axonal microtubules in growing neurites has been a controversial issue because of clear but conflicting results obtained with fluorescence-marking techniques. We have attempted to resolve the discordance via analysis of the relationship between apparent microtubule translocation and cell adhesion. Neuronal cultures were prepared from Xenopus embryos 1 d after injection of Cy3-conjugated tubulin into one of the blastomeres of two-cell-stage embryos. Anterograde translocation of axonal microtubules was observed in neurons cultured on a laminin-coated surface, in agreement with previously published data for Xenopus embryonic neurons. However, when neuronal cultures were prepared on a concanavalin A-treated surface, the axonal microtubules were stationary, as reported for all other neurons investigated previously. Neuronal cultures prepared on laminin- and concanavalin A-coated surfaces also demonstrated dramatic differences in the pattern of axonal growth, dynamics of axonal microtubules, and response to brefeldin A treatment. Our findings suggest that transport and dynamics of axonal microtubules may be directly affected by the mechanical tension produced by growth cone activity.
Animals↗
Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost +/- hyperthermia for glioblastoma multiforme.
PURPOSE: To determine if adjuvant interstitial hyperthermia (HT) significantly improves survival of patients with glioblastoma undergoing brachytherapy boost after conventional radiotherapy. METHODS AND MATERIALS: Adults with newly-diagnosed, focal, supratentorial glioblastoma < or = 5 cm in diameter were registered postoperatively on a Phase II/III randomized trial and treated with partial brain radiotherapy to 59.4 Gy with oral hydroxyurea. Those patients whose tumor was still implantable after teletherapy were randomized to brachytherapy boost (60 Gy at 0.40-0.60 Gy/h) +/- HT for 30 min immediately before and after brachytherapy. Time to progression (TTP) and survival from date of diagnosis were estimated using the Kaplan-Meier method. RESULTS: From 1990 to 1995, 112 eligible patients were entered in the trial. Patient ages ranged from 21-78 years (median, 54 years) and KPS ranged from 70-100 (median, 90). Most commonly due to tumor progression or patient refusal, 33 patients were never randomized. Of the patients, 39 were randomized to brachytherapy ("no heat") and 40 to brachytherapy + HT ("heat"). By intent to treat, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.04 and p = 0.04). For the 33 "no heat" patients and 35 "heat" patients who underwent brachytherapy boost, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.045 and p = 0.02, respectively; median survival 85 weeks vs. 76 weeks; 2-year survival 31% vs. 15%). A multivariate analysis for these 68 patients adjusting for age and KPS showed that improved survival was significantly associated with randomization to "heat" (p = 0.008; hazard ratio 0.51). There were no Grade 5 toxicities, 2 Grade 4 toxicities (1 on each arm), and 7 Grade 3 toxicities (1 on "no heat" and 6 on the "heat" arm). CONCLUSION: Adjuvant interstitial brain HT, given before and after brachytherapy boost, after conventional radiotherapy significantly improves survival of patients with focal glioblastoma, with acceptable toxicity.
Adult↗
Neovascular complications associated with rubeosis iridis and peripheral retinal detachment after retinal detachment surgery.
PURPOSE: To report clinical features and surgical management of neovascular complications associated with rubeosis iridis and peripheral retinal detachment after retinal detachment surgery in nondiabetic patients. METHODS: Seven consecutive eyes of seven nondiabetic patients who developed neovascular complications associated with rubeosis iridis and peripheral retinal detachment after scleral buckling and vitrectomy procedures were retrospectively reviewed. None of the eyes had clinical evidence of anterior segment ischemia or retinal vascular disease, but each eye developed rubeosis iridis and neovascular complications. RESULTS: Of the seven eyes with rubeosis iridis and peripheral retinal detachment, six developed recurrent or progressive vitreous hemorrhage, and three developed progressive neovascular glaucoma. Four eyes underwent a revision procedure to repair the peripheral retinal detachment, and anterior proliferative vitreoretinopathy was found in each of these cases. Rubeosis iridis regressed in all three eyes in which surgery resulted in complete reattachment of the retina. In one eye with persistent peripheral retinal detachment and in the three remaining eyes that did not undergo revision surgery, rubeosis iridis persisted and was associated with long-term neovascular complications. Final corrected visual acuity was 20/70 to 20/400 in three eyes with total retinal reattachment and no light perception to hand motions in four eyes with persistent peripheral retinal detachment and rubeosis iridis. CONCLUSION: Visually significant neovascular complications may occur in eyes that develop rubeosis iridis associated with peripheral retinal detachment after retinal detachment surgery in nondiabetic patients. Successful repair of the peripheral retinal detachment may induce regression of rubeosis iridis, reduce associated complications, and improve the long-term prognosis of these eyes.
Adult↗
Constitutive secretion of exogenous neurotransmitter by nonneuronal cells: implications for neuronal secretion.
Fibroblasts in cell culture were loaded with exogenous neurotransmitter acetylcholine (ACh). ACh secretion from loaded cells was detected by whole-cell patch clamp recordings from Xenopus myocytes manipulated into contact with ACh-loaded cells. Two different approaches were used for ACh loading. In the first approach, fibroblasts were incubated in the culture medium containing ACh. Recordings from myocytes revealed fast inward currents that resemble miniature endplate currents found at neuromuscular synapses. The currents observed in recordings from myocytes were due to exocytosis of ACh-containing vesicles. Although exogenous ACh penetrated through the plasma membrane of fibroblasts during incubation and was present in the cytoplasm at detectable levels, cytoplasmic ACh did not contribute to the quantal ACh secretion. In the second approach, exogenous ACh was loaded into the cytoplasm of fibroblasts by microinjection. Under these experimental conditions, fibroblasts also exhibited spontaneous quantal ACh secretion. Analysis of the exocytotic events in fibroblasts following two different protocols of ACh loading revealed that the vesicular compartments responsible for uptake of exogenous ACh are associated with the endocytic recycling pathway. Extrapolation of our results to neuronal cells suggest that in cholinergic neurons, in addition to genuine synaptic vesicles, ACh can be secreted by the vesicles participating in endosomal membrane recycling.
Acetylcholine↗
Evaluation of drug usage and expenditure in a hospital diabetes clinic.
BACKGROUND: Diabetes mellitus is a major public health problem and often coexists with hypertension and dyslipidaemia. A prescription-based survey was conducted to examine the use of antidiabetic, antihypertensive and lipid lowering drugs in a hospital diabetes clinic. The expenditure incurred was also evaluated. METHOD: Prescriptions issued from the diabetes clinic were collected for 4 consecutive weeks. Drugs were categorized into three main classes--antidiabetic, antihypertensive and lipid-lowering drugs. The unit cost of each drug and the total amount prescribed were used to estimate the total drug costs. RESULTS: During the 4-week study period, 534 prescriptions were collected, of which 520 contained antidiabetic drugs. Oral hypoglycaemic agents were prescribed in 379 patients (72.9%). Sulphonylurea was used as a single agent in 119 (22.9%) patients, in combination with metformin in 219 (42%) patients and with insulin in 17 patients (3.3%). Among patients treated with sulphonylureas (n=342), glibenclamide (47.7%) and gliclazide (30.7%) were the main drugs prescribed. Metformin monotherapy was prescribed in only 31 patients (6%). Insulin treatment was prescribed in 141 (27%) patients and in combination with oral drugs in 23 patients (4.5%). Of the 534 prescriptions, 225 (42%) contained antihypertensive drugs. Calcium channel blocking agents and angiotensin converting enzyme inhibitors were the most commonly prescribed drugs in both monotherapy (n=155) and combination therapy (n=70). The antidiabetic and antihypertensive drugs accounted for 45% and 39% of the total drug expenditure, respectively. Lipid-lowering drugs were prescribed in 8% of the diabetic patients. Simvastatin and gemfibrozil were the most common drugs prescribed and accounted for 12% of the total drug expenditure. CONCLUSION: The use of antidiabetic drugs represents a major burden on the health care system. The high proportions of patients requiring antihypertensive drugs and lipid lowering drugs further increase drug expenditure. Most of these treatments have been shown to improve clinical outcomes and quality of life, if used appropriately. The impacts of these long-term medications on health care financing require careful evaluation to assess their cost-effectiveness.
Adult↗
Drug utilization in a hospital general medical outpatient clinic with particular reference to antihypertensive and antidiabetic drugs.
OBJECTIVES: To examine the prescribing patterns, particularly antihypertensive and antidiabetic drugs, in a hospital outpatient clinic and to evaluate the expenditure incurred. METHODS: Prescriptions from a general medical outpatient clinic in a teaching hospital were collected for 4 weeks. Drug expenditures were calculated. RESULTS: A total of 622 prescriptions containing 1903 items were collected. Antihypertensive and antidiabetic drugs accounted for 25.9 and 9.1% usage, respectively. Calcium channel blocking agents, angiotensin converting enzyme inhibitors and beta-blocking agents were the most popular antihypertensive drugs used. Sulphonylureas were the most frequently prescribed antidiabetic agents. Amlodipine, doxazosin and sotalol accounted for 4.5% of all prescription items but 27.8% of the total drug expenditure. CONCLUSION: The use of antihypertensive and antidiabetic drugs accounted for most of the drug usage in this study. Use of newer and more expensive agents has further increased drug expenditure. Monitoring drug usage and their correlations with clinical outcomes are warranted.
Aged↗
Use of indapamide in hospital and community clinics and its effect on plasma potassium in Chinese patients.
OBJECTIVES: To investigate the usage pattern of indapamide and other antihypertensive drugs in patients attending a community-based government outpatient clinic (GOPC) or a hospital-based specialist clinic (SC). The plasma potassium concentrations of patients receiving indapamide and other diuretics were also examined. METHOD: Prescriptions from the SC and the GOPC were reviewed and collected during January 1998. Patients' plasma potassium concentrations and the date of initiation of each medication were retrieved from the hospital computer databases at SC. An age- and sex-matched control group of patients on non-diuretic antihypertensive drugs was identified. RESULTS: A total of 1648 and 773 prescriptions were collected from the SC during a 1-week period and GOPC during a 1-month period, respectively. Approximately half (45%) of the patients received antihypertensive treatment. Indapamide was five times more frequently prescribed in GOPC than SC (84.7 vs. 17.7%, P<0.001). Calcium channel blocking agents were the commonest antihypertensive drugs used in both clinics. The mean plasma potassium concentration of patients taking indapamide was lower than that of the control group (P = 0.037). Multiple linear regression analysis showed that consumption of indapamide (P =0.002) and duration of diuretic therapy (P = 0.023) were significantly related to changes in plasma potassium concentrations [multiple regression equation for potassium level = 4.09-0.145 (thiazide = 1)-0.377 (indapamide = 1) -0.00468 (duration of diuretic therapy in months)]. CONCLUSION: Indapamide was used extensively in the community clinic and less in the hospital-based outpatient clinic. Patients receiving indapamide had a significantly lower plasma potassium concentration as compared to other diuretics or antihypertensive groups and this was predicted by a multiple linear regression model. Monitoring plasma electrolytes before initiation of indapamide treatment and at regular intervals thereafter is essential for detecting the hypokalaemia that may occur in Chinese patients.
Aged↗
Analysis of epitope spreading over an eleven-year period in a patient with systemic lupus erythematosus.
During a period of more than eleven years serum samples of a patient with Systemic Lupus Erythematosus were collected and analyzed for anti-nuclear autoantibodies. High titer of anti-La/SS-B were detectable in all serum samples. The La/SS-B epitopes remained constant. Besides anti-La/SS-B antibodies all serum samples contained traces of anti-Ro/SS-A including anti-Ro52 and anti-Ro60 antibodies. During disease flares anti-Ro/SS A antibodies were upregulated and anti-dsDNA antibodies appeared, thus supporting the concept of an antigen driven intermolecular epitope spreading to Ro/SS-A and dsDNA.
Adult↗