Lymphadenopathy after joint replacement for osteoclastoma.
Explore the source record for details and available documents.
Foreign-Body Reaction↗
Biomedical subjects
A J Stewart
Publications and source records attributed to A J Stewart.
Frovatriptan: a review of drug-drug interactions.
OBJECTIVE: To investigate the potential for interactions involving drugs likely to be coadministered with frovatriptan. BACKGROUND: Frovatriptan is a new 5-hydroxytryptamine (5-HT)(1B/1D) agonist. Preclinical data suggest that the pharmacokinetic and pharmacological profile of frovatriptan may differ from that of the currently available triptans. METHODS: The potential for interactions between frovatriptan and other drugs was investigated using in vitro methods, studies in healthy volunteers, and retrospective analysis of data from phase I trials. RESULTS: In vitro, frovatriptan was principally metabolized by cytochrome P-450 (CYP) 1A2 but was found not to be an inhibitor or inducer of this or other CYP isoenzymes. Frovatriptan was only a weak inhibitor of monoamine oxidase at very high concentrations in vitro and was not a substrate for this enzyme (unlike some other triptans). Coadministration with moclobemide, at doses known to inhibit monoamine oxidase-A, did not affect the pharmacokinetics of frovatriptan. Binding to plasma proteins was low (15%), and binding to erythrocytes was moderate (60%) and unlikely to be a source of interaction with other drugs. The pharmacokinetics of frovatriptan were not affected by moderate alcohol intake. There were slight increases in area under the curve and maximum concentration on concomitant administration with the combined oral contraceptives, propranolol, and fluvoxamine; and slight decreases in these parameters on concomitant administration with ergotamine and in tobacco smokers; these findings were considered to have no clinical significance in view of frovatriptan's large therapeutic index (well tolerated at doses ranging from 2.5 to 40 mg). These effects can be attributed primarily to modification of CYP1A2 activity but their impact is limited, probably due to frovatriptan also undergoing renal clearance and the likely role of blood cell binding in controlling the amount of unbound drug available for elimination. CONCLUSIONS: Because it has no inhibitory or inducing effect on CYP isoenzymes and is only slightly bound to plasma proteins, it is unlikely that frovatriptan will alter the pharmacokinetics of concomitantly administered drugs. Frovatriptan, therefore, appears to have a low risk of interaction with other drugs, and adjustments of dose are unlikely to be required when it is coadministered with other agents.
Acute Disease↗
Coeliac disease following high-dose chemotherapy.
This report describes an interesting case of severe diarrhoea following high-dose chemotherapy for non-Hodgkin's lymphoma. This caused significant morbidity and resolved on a gluten-free diet.
Antineoplastic Combined Chemotherapy Protocols↗
Intracardiac thrombus traversing a patent foramen ovale: impending paradoxical embolism demonstrated by transoesophageal echocardiography.
Paradoxical embolism is a rare but potentially catastrophic complication of deep venous thromboses and pulmonary embolism. We describe a patient in whom transoesophageal echocardiography demonstrated a large clot traversing the atrial septum which was successfully removed by surgery.
Echocardiography, Transesophageal↗
Dicationic bis(9-methylphenazine-1-carboxamides): relationships between biological activity and linker chain structure for a series of potent topoisomerase targeted anticancer drugs.
Bis(9-methylphenazine-1-carboxamides) joined by a variety of dicationic (CH(2))(n)()NR(CH(2))(m)NR(CH(2))(n) linkers of varying length (carboxamide N-N distances from 11.0 to 18.4 A) and rigidity were prepared by reaction of 9-methylphenazine-1-carboxylic acid imidazolide with the appropriate polyamines. The compounds were evaluated for growth inhibitory properties in P388 leukemia, Lewis lung carcinoma, and wild-type (JL(C)) and mutant (JL(A) and JL(D)) forms of human Jurkat leukemia with low levels of topoisomerase II (topo II). The compounds all had IC(50) ratios of <1 in the resistant Jurkat lines, consistent with topo II inhibition not being the primary mechanism of action. Analogues joined by an (CH(2))(2)NR(CH(2))(2)NR(CH(2))(2) linker were extremely potent cytotoxins, with selectivity toward the human cell lines, but absolute potencies declined sharply from R = H through R = Me to R = Pr and Bu. In contrast, (CH(2))(2)NR(CH(2))(3)NR(CH(2))(2) compounds showed reverse effects, with the R = Me analogue being more potent than the R = H one as well as being the most potent in the series [IC(50) in JL(C) cells 0.08 nM; superior to that for the clinical bis(naphthalimide) LU 79553]. Overall, the IC(50)s of analogues with linker chains (CH(2))(n)NH(CH(2))(m)NH(CH(2))(n) were inversely proportional to linker length. Constraining the rigidity of the linker chain by incorporating a piperazine ring did not decrease potency significantly. A representative compound bound tightly to DNA with high selectivity for GC sites, compatible with recent work suggesting that compounds of this type place their side chains in the major groove, making specific contacts with guanine bases. Representative compounds were susceptible to transport mediated resistance, being much less effective in cells that overexpressed P-glycoprotein. Overall the results suggest these compounds have a similar mode of action, mediated primarily by poisoning of topo I (possibly with some involvement of topo II). The bis(9-methylphenazine-1-carboxamides) show very high in vitro growth inhibitory potencies compared to their monomeric analogues. Two compounds showed in vivo activity in murine colon 38 syngeneic and HT29 human colon tumor xenograft models using intraperitoneal dosing.
Amides↗
In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576.
The overexpression of P-glycoprotein (P-gp) on the surface of tumor cells causes multidrug resistance (MDR). This protein acts as an energy-dependent drug efflux pump reducing the intracellular concentration of structurally unrelated drugs. Modulators of P-gp function can restore the sensitivity of MDR cells to such drugs. XR9576 is a novel anthranilic acid derivative developed as a potent and specific inhibitor of P-gp, and in this study we evaluate the in vitro and in vivo modulatory activity of this compound. The in vitro activity of XR9576 was evaluated using a panel of human (H69/LX4, 2780AD) and murine (EMT6 AR1.0, MC26) MDR cell lines. XR9576 potentiated the cytotoxicity of several drugs including doxorubicin, paclitaxel, etoposide, and vincristine; complete reversal of resistance was achieved in the presence of 25-80 nM XR9576. Direct comparative studies with other modulators indicated that XR9576 was one of the most potent modulators described to date. Accumulation and efflux studies with the P-gp substrates, [3H]daunorubicin and rhodamine 123, demonstrated that XR9576 inhibited P-gp-mediated drug efflux. The inhibition of P-gp function was reversible, but the effects persisted for >22 h after removal of the modulator from the incubation medium. This is in contrast to P-gp substrates such as cyclosporin A and verapamil, which lose their activity within 60 min, suggesting that XR9576 is not transported by P-gp. Also, XR9576 was a potent inhibitor of photoaffinity labeling of P-gp by [3H]azidopine implying a direct interaction with the protein. In mice bearing the intrinsically resistant MC26 colon tumors, coadministration of XR9576 potentiated the antitumor activity of doxorubicin without a significant increase in toxicity; maximum potentiation was observed at 2.5-4.0 mg/kg dosed either i.v. or p.o. In addition, coadministration of XR9576 (6-12 mg/kg p.o.) fully restored the antitumor activity of paclitaxel, etoposide, and vincristine against two highly resistant MDR human tumor xenografts (2780AD, H69/LX4) in nude mice. Importantly all of the efficacious combination schedules appeared to be well tolerated. Furthermore, i.v. coadministration of XR9576 did not alter the plasma pharmacokinetics of paclitaxel. These results demonstrate that XR9576 is an extremely potent, selective, and effective modulator with a long duration of action. It exhibits potent i.v. and p.o. activity without apparently enhancing the plasma pharmacokinetics of paclitaxel or the toxicity of coadministered drugs. Hence, XR9576 holds great promise for the treatment of P-gp-mediated MDR cancers.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
A simple stream monitoring technique based on measurements of semiconservative properties of water.
Correlative relationships exist among conductivity, alkalinity, and hardness in streams due to natural geological and climatological controls, but the relationships among these three water-quality factors can be altered strongly by inputs of ion-rich wastewaters. The degree of alteration can be monitored conveniently by use of a simple chemical perturbation index, computed by subtracting the sum of rank pairwise correlations among the conductivity, alkalinity, and hardness (for observations on each of these variables, measured through time) from 3.0. The chemical perturbation index can be used to document or characterize spatiotemporal changes in stream water quality. This study explains the development of the index's concept and provides examples of its application in an extensive stream monitoring program used to assess ecological conditions in streams on the Department of Energy's Oak Ridge Reservation in east Tennessee, USA. The chemical perturbation index technique may be particularly useful in community-based stream monitoring programs because to its simplicity and low cost.
Animals↗
Effects of development time, biomass and ferromanganese oxides on nickel sorption by stream periphyton.
Procedurally defined periphyton frequently includes substantial quantities of hydrous iron (Fe) and manganese (Mn) oxides. As these oxides are strong sorbers of heavy metals, their presence may complicate estimation of metal bioaccumulation by periphyton. We examined the relationship between nickel (Ni) sorption and the development time, biomass, and Fe and Mn oxide content of stream periphyton. Development time, the time during which periphyton accrued on submerged tile substrata, was used to provide variation in biomass, Fe and Mn levels. Stream periphyton from four development times was exposed to Ni for 2 h in the laboratory, and then ashed. Development time was significantly associated with ash-free dry mass (AFDM), Fe and Mn levels (ANOVA, P < or = 0.003). Ni extracted by a mild reductant (hydroxylamine hydrochloride) was significantly associated with development time, and with AFDM, Fe and Mn levels (linear models, P < or = 0.0002). A subsequent acid digestion yielded similar associations with the same variables (linear models, P < or = 0.0001). For both extractions, AFDM was significantly and positively correlated with Fe (r = 0.68 and 0.89) and with Mn (r = 0.77 and 0.93) (Spearman rank, P < or = 0.005). These data demonstrate the importance of periphyton development time in influencing both metal sorption and levels of biomass and ferromanganese oxides. The data also suggest that metal contaminant levels in periphyton should not be attributed automatically to biotic sorption. Periphyton metal-accumulation studies conducted where ferromanganese oxide concentrations are elevated should address the potential metal-sorbing roles of Fe and Mn oxides within the periphyton matrix.
Absorption↗
Integrating text and pictorial information: eye movements when looking at print advertisements.
Viewers looked at print advertisements as their eye movements were recorded. Half of them were told to pay special attention to car ads, and the other half were told to pay special attention to skin-care ads. Viewers tended to spend more time looking at the text than the picture part of the ad, though they did spend more time looking at the type of ad they were instructed to pay attention to. Fixation durations and saccade lengths were both longer on the picture part of the ad than the text, but more fixations were made on the text regions. Viewers did not alternate fixations between the text and picture part of the ad, but they tended to read the large print, then the smaller print, and then they looked at the picture (although some viewers did an initial cursory scan of the picture). Implications for (a) how viewers integrate pictorial and textual information and (b) applied research and advertisement development are discussed.
Adult↗
Characterizing concerns about post-cessation weight gain: results from a national survey of women smokers.
Differences among adult women smokers with differing levels of concern about post-cessation weight gain were investigated in a national random-digit-dialing survey. To avoid defining weight concerns in terms of possible etiologies or contributory factors, respondents were stratified using a single item querying concern about post-cessation weight gain; 39% described themselves as very concerned (VC), 28% as somewhat concerned (SC), and 33% as not concerned (NC). Significant between-groups differences were detected for measures of weight and body image, eating patterns and weight control practices, and nicotine dependence, but not for depression. Differences, primarily between VC and NC, were also detected for several weight-related smoking variables, including importance of weight as a factor in initiation, smoking as a weight control strategy, increased appetite and weight gain as withdrawal symptoms, willingness to gain weight upon quitting, self-efficacy about relapse in the face of weight gain, and readiness to quit smoking. Most differences persisted even after adjusting for body mass index and nicotine dependence. Although the importance of thinness was rated higher by weight-concerned women, the difference did not reach significance. Rather, what differentiated groups was the importance of overall body image, suggesting a larger pattern of preoccupation with body image that may not be captured by queries about weight concerns alone. We conclude that weight-concerned women smokers will be especially unlikely to seek treatment or attempt self-quitting; and that redirecting attention to other aspects of body image is likely to be more helpful than attempting to divert attention away from body image.
Adolescent↗
Antitumor activity of XR5944, a novel and potent topoisomerase poison.
Inhibitors of topoisomerases are widely used in the treatment of cancer, including inhibitors of topoisomerase I (camptothecin analogs such as irinotecan and topotecan) and topoisomerase II (etoposide and doxorubicin). The novel bis-phenazine, XR5944, is a joint inhibitor of topoisomerase I and II as shown by the stabilization of topoisomerase-dependent cleavable complexes. XR5944 demonstrated exceptional activity against human and murine tumor cells in vitro and in vivo. In a range of cell lines XR5944 (IC50 0.04-0.4 nM) was significantly more potent than TAS-103, originally proposed as a joint topoisomerase I and II inhibitor, as well as agents specific for topoisomerase I or II (topotecan, doxorubicin and etoposide). In addition, XR5944 was unaffected by atypical drug resistance and retained significant activity in cells overexpressing P-glycoprotein or multidrug resistance-associated protein. Antitumor efficacy of XR5944 was demonstrated in human carcinoma xenograft models (H69 small cell lung cancer and HT29 colon). In the HT29 model, which is relatively unresponsive to chemotherapy, XR5944 (15 mg/kg i.v., q4dx3) induced tumor regression in the majority of animals (six of eight), whereas TAS-103, dosed at its maximum tolerated dose (45 mg/kg i.v., q7dx3), only induced a delay in tumor growth compared with control animals. In the H69 model, low doses of XR5944 (5 mg/kg i.v., qdx5/week for 2 weeks or 10-15 mg/kg i.v., q4dx3), induced complete tumor regression in the majority of animals. In contrast, topotecan (20 mg/kg i.v., q4dx3) or etoposide (30 mg/kg i.v., q5dx5) only slowed the tumor growth rate. These studies show that XR5944 is a highly active novel anticancer agent that is well tolerated at efficacious doses.
Aminoquinolines↗
The effect of fathers or father figures on child behavioral problems in families referred to child protective services.
This study examines some possible effects of the presence and quality of parent-child interaction of fathers and father figures on the behavior of young children in a sample of families reported to child protective services. Whereas the presence or absence of a father or father figure seemed to make little difference in child behavioral problems at age 4, lower levels of aggression and depression were observed for children by age 6 if an adult male in some form of father-like relationship was present in the child's life. When controlling for mother's ethnicity, child's gender, the number of referrals to child protective services, and the presence of domestic violence, the direct effect of a father/father figure was no longer significant but remained in the multivariate models as a significant interaction term.
Adult↗
Effects of endophyte status of tall fescue tissues on the earthworm (Eisenia fetida).
A cryptic fungal endophyte, Neotyphodium coenophialum, infects most tall fescue (Festuca arundinacea) pastures in the United States. Cattle, sheep, and horses that consume the endophyte-infected grass can suffer fescue toxicosis caused by toxic alkaloids in the infected plants. The effects of the endophyte on mammalian herbivores have been well documented, but less is known regarding the quality of the grass (infected vs noninfected) as a food material for soil invertebrates. We conducted 21-d tests with earthworms (Eisenia fetida) to determine the nutritional quality of endophyte-infected and noninfected tall fescue leaf and root tissues. Earthworm survival, growth, and reproduction were measured in each treatment combination of tissue type and infection status. Earthworm survival was 100% in all treatments. Tall fescue tissue type (leaf vs root) and infection status (present or absent) both significantly affected E. fetida growth and reproduction. The earthworms grew and had moderate levels of reproduction in replicates containing tall fescue leaf tissue as the sole food source regardless of the endophyte-infection status, but earthworms lost weight and had less reproduction in replicates where tall fescue root tissue was the sole food source. An unexpected effect of infection status on earthworm growth in the tall fescue leaf-tissue treatments was also evident: mean growth of E. fetida with access to endophyte-infected leaf tissue as the sole food source was 3.6-fold greater than mean growth of E. fetida with access to noninfected leaf tissue as the sole food source. Knowledge regarding the relative effects of endophyte status of tall fescue on soil organisms may allow the development of more effective environmental management strategies at sites where tall fescue is being considered for use in phytoremediation or for vegetative cover. Investigators working with tall fescue should be alert to the possibility of endophyte-mediated effects of tall fescue on other organisms and, at a minimum, should provide information regarding the grass's infection status when reporting the results of studies that involve use of tall fescue.
Animals↗
Occurrence of flavonols in tomatoes and tomato-based products.
The flavonol contents of 20 varieties of tomato fruit were investigated in relation to variety, size, season, and country of origin. Ten commonly consumed tomato-based food products were also assessed. Free and conjugated flavonols were identified and quantified using reversed-phase HPLC. Ninety-eight percent of flavonols detected in tomatoes were found to occur in the skin. Tomatoes contained, primarily as conjugates, quercetin and kaempferol. The main quercetin conjugate was identified as rutin (quercetin 3-rhamnosylglucoside) by LC-MS. The total flavonol content of the different varieties of tomato that were analyzed varied from 1.3 to 22.2 microgram/g of fresh weight (fw). Smaller cherry tomato fruits originating from warm sunny climates, such as Spain and Israel, were found to contain the highest concentration of flavonols. Among the tomato-based products investigated, tomato juice and tomato purée were rich in flavonols, containing 14-16 microgram/mL and 70 microgram/g fw, respectively. In contrast to fresh tomatoes, most tomato-based products contained significant amounts of free flavonols.
Chromatography, High Pressure Liquid↗
Activation of syntactic information during language production.
In order to produce utterances, people must draw upon syntactic information. This paper considers how evidence from syntactic priming experiments casts light upon the nature of syntactic information activation during language production. We examine three issues: the way in which syntactic information is initially activated, the circumstances under which activation may persist or dissipate, and the effects of residual activation of syntactic information on subsequent language production. Evidence from dialog experiments suggests that the information that is initially activated is the same in both production and comprehension. Evidence about the persistence of activation following initial activation is more complex. We suggest that persistence may be related to the potential relevance of the information for subsequent syntactic processing. We show that current evidence is inconclusive about how long syntactic information remains activated.
Cognition↗
Thrombosis in a duplicated superficial femoral vein in a patient with haemophilia A.
Venous thrombosis is a very rare occurrence in patients with haemophilia A. We report the case of a haemophiliac in whom initially a calf haematoma was suspected, but neither this nor deep venous thrombosis (DVT) could be confirmed on ultrasound scanning. Subsequently, a high segment venous thrombosis was diagnosed by venography in a portion of a duplicated superficial femoral vein. Treatment with factor VIII (FVIII) and low molecular weight heparin led to a successful resolution. The only other case we have been able to find in the literature occurred during FVIII replacement therapy, which was not the situation with our patient.
Adult↗
Acquired haemophilia in recipients of depot thioxanthenes.
We present two cases in which the occurrence of acquired haemophilia is associated with the use of depot preparations of the thioxanthenes zuclopenthixol and flupenthixol. These drugs have not previously been implicated in the aetiology of acquired haemophilia.
Adult↗
Syntactic priming in spoken production: linguistic and temporal interference.
Current evidence about the persistence of syntactic priming effects (Bock, 1986) is equivocal: Using spoken picture description, Bock and Griffin (2000) found that it persisted over as many as 10 trials; using written sentence completion, Branigan, Pickering, and Cleland (1999) found that it dissipated if even a single sentence intervened between prime and target. This paper asks what causes it to be long lasting. On one account, the rapid decay evidenced by Branigan et al. occurs because the task emphasizes conceptual planning; on another account, it is due to the written nature of their task. If conceptual planning is the cause, this might relate to planning the prime sentence or planning an intervening sentence. Hence we conducted an experiment with spoken sentence completion, contrasting no delay, an intervening sentence, and a pure temporal delay. The results indicated that strong and similar priming occurred in all three cases, therefore lending support to the claim that spoken priming is long lasting.
Adult↗