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Stability of methylecgonidine and ecgonidine in sheep plasma in vitro.

BACKGROUND: Crack smokers are exposed to a pyrolysis product, methylecgonidine (MEG), which can be used as an analytical marker for crack smoking. Ecgonidine (EC), a hydrolytic product of MEG, has been identified in urine of crack smokers. MEG undergoes conversion to EC, complicating analysis and perhaps explaining a lack of forensic blood specimens containing MEG. METHODS: We developed gas chromatography-mass spectrometry (GC-MS) assays for MEG and EC. Plasma was collected from sheep blood containing 0, 0.06, or 0.24 mol/L (0%, 0.25%, or 1%) NaF. MEG was added to these plasmas, and they were incubated at -80, 1, 21, or 37 degrees C to determine whether there were temporal, temperature, or storage effects on MEG stability over 48 h. RESULTS: Decreased temperature and increased NaF concentrations limited MEG degradation and EC formation. MEG stored in plasma at -80 degrees C was stable up to 1 month, even in the absence of NaF. CONCLUSIONS: MEG is stable in sheep plasma collected in commercially available, evacuated blood-collection tubes containing NaF and stored at -80 degrees C. In vitro formation of EC can be minimized with appropriate sample handling, and its in vivo formation may provide a better marker of crack smoking than its parent pyrolysis product.

Animals↗

[Pharmacokinetics of C14-olivomycin in the body of mice with lymphosarcoma (L10-1 strain)].

The pharmacokinetics of C14-olivomycin after its single intravenous administration to mice with lymphosarcome (LIO-I) was studied. It was shown that according to the specific radioactivity the organs may be placed in the following order: I hour after the antibiotic administration-the blood, liver, spleen, thymus, tumor, muscle; 3 hour after the administration-the liver, spleen, thymus, blood, tumor, muscle. Accumulation of olivomycin in the mouse organs was mainly in direct dependence on the dose of the antibiotic administered. Chromatography of the substances extraceted with ethylacetate from the urine collected at various periods after C14-olivomycin administration showed the presence of a new radioactive product (Rf 0.35-0.37) in addition to the unchanged antibiotic (Rf 0.53). Bioautographic analysis of the chromatograms showed that the product of C14-olivomycin conversion preserved its biological activity. The analysis of the substances extracted with ethylacetate from the liver, spleen and tumors 3 hours after the antibiotic administration reveiled (except of the liver) the presence of a spot with Rf corresponding to that of the initial drug.

Animals↗

Laparoscopic cholecystectomy: relationship of pathology and operative time.

OBJECTIVE: Controversy exists regarding the use and timing of laparoscopic cholecystectomy in the treatment of both acute and chronic cholecystitis. Acute advocates claim to avoid fibrosis and potential dissection injuries, whereas chronic proponents avoid poor visualization due to edema and possible conversion. This study of both acute and chronic cholecystitis cases examines the relationships between pathology, operative time, and outcome of laparoscopic cholecystectomy. METHODS: A retrospective review of medical records and pathology of acute (n = 9) and chronic (n = 62) laparoscopic cholecystectomy cases, performed by 2 surgeons from 1995 to 1999 was undertaken. Using multiple regression techniques, the relationship between operative time and age, sex, race, presenting symptoms, and degree of pathologic cholecystitis was evaluated. RESULTS: One case of acute gangrenous cholecystitis required conversion. None of the chronic cases required conversion. In single variable analysis, abnormal liver function tests, chronic inflammation, wall thickness, and number of stones were each predictive of longer operative time. However, in the multiple regression, abnormal liver function tests were the only clinical factor that remained a predictor of operative time (16 minutes longer, P = 0.05). Time from presentation to operation had no effect on operative time. Twelve patients had preoperative endoscopic retrograde cholangiopancreatography, and 4 had choledocholithiasis (acute n = 1, chronic n = 3). Two chronic patients required postoperative endoscopy for a cystic duct leak (n = 1) and choledocholithiasis (n = 1). The adjusted average operative time for acute and chronic cases was similar (93 versus 74 minutes, P > 0.05). CONCLUSION: Laparoscopic cholecystectomy can be done safely for both acute and chronic cholecystitis with similar operative times. Abnormal liver function tests are associated with longer operative time. Time lapse between presentation and operation has no effect on operative time or outcome.

Adult↗

Psychophysiological effects of stimulation with pictures of works of art in old age.

The present article reports on a controlled intervention study concerning the effects of non-directed use of pictures of works of art as a way of stimulating institutionalized elderly women. After the stimulation period differences in ratings between the groups indicated improved well-being in the intervention group. Such improvement was not seen in the C-group. The quantitative analyses of the results reveal a significant change of the parameters happiness, peacefulness, creativeness, social activities and systolic blood pressure. The qualitative analysis shows that the conversations about pictures of works of art in the intervention group give the person free rein to her own imagination and are merely characterized by happiness. In the control group the conversations are to a great extent characterized by downheartedness, despair and complaining.

Aged↗

Effect of light activation method on flexural properties of dental composites.

PURPOSE: To determine if irradiating composites in a laboratory tungsten-halogen light-curing unit produced equal flexural properties to stepwise hand-curing with a tungsten-halogen lamp. METHODS: Bars (n = 10) of nine commercial composites were formed by light-curing in square glass tubes (2 x 2 x 25 mm). Flexure strength (FS, MPa) and flexure modulus (FM, GPa) were tested in three-point bending after aging specimens in water at 37 degrees C for 1 day. Two methods were used to irradiate the composites: a) Triad II (Dentsply) using 40-second exposures from top and bottom; and b) Optilux 400 (Demetron; 600 mW/cm2) using 3 x 40 seconds overlapping exposures from the top only. Filler wt% was determined by thermal gravimetric analysis. The degree of conversion (DC) of each composite cured with the two techniques was evaluated by micro-FTIR. T-tests were performed for FS and FM to compare Triad II vs Optilux for each composite (alpha < 0.05). RESULTS: There was a trend for Optilux to produce greater FS (significant for A110, Herculite and P60) and FM (significant for all but Clearfil, Esthet-X and Z250), but differences averaged less than 10%. There was no difference in DC between the irradiation modes for any composite.

Acrylic Resins↗

Cellular interactions between n-6 and n-3 fatty acids: a mass analysis of fatty acid elongation/desaturation, distribution among complex lipids, and conversion to eicosanoids.

The biologic effect of eicosanoids depends in large measure upon the relative masses in tissues of eicosanoids derived from the n-6 fatty acids, dihomogammalinolenic acid and arachidonic acid, and the n-3 fatty acid, eicosapentaenoic acid. Generation of this tissue balance is related to the relative cellular masses of these precursor fatty acids, the competition between them for entry into and release from cellular phospholipids, and their competition for the enzymes that catalyze their conversion to eicosanoids. In order to better understand these processes, we studied the cellular interactions of n-6 and n-3 fatty acids using an essential fatty acid-deficient, PGE-producing, mouse fibrosarcoma cell line, EFD-1. Unlike studies using cells with endogenous pools of n-6 and n-3 fatty acids, the use of EFD-1 cells enabled us to examine the metabolic fate of each family of fatty acids both in the presence and in the absence of the second family of fatty acids. Thus, the specific effects of one fatty acid family on the other could be directly assessed. In addition, we were able to replete the cells with dihomogammalinolenic acid (DHLA), arachidonic acid (AA), and eicosapentaenoic acid (EPA) of known specific activities; thus the masses of cellular DHLA, AA, and EPA, and their metabolites, PGE1, PGE2, and PGE3, respectively, could be accurately quantitated. The major findings of this study were: 1) n-6 fatty acids markedly stimulated the elongation of EPA to 22:5 whereas n-3 fatty acids inhibited the delta 5 desaturation of DHLA to AA and the elongation of AA to 22:4; 2) n-6 fatty acids caused a specific redistribution of cellular EPA from phospholipid to triacylglycerol; 3) n-3 fatty acids reduced the mass of DHLA and AA only in phosphatidylinositol whereas n-6 fatty acids reduced the mass of EPA to a similar extent in all cellular phospholipids; and 4) n-3 fatty acids caused an identical (33%) reduction in the bradykinin-induced release of PGE1 and PGE2, whereas n-6 fatty acids stimulated PGE3 release 2.3-fold. Together, these highly quantitative metabolic data increase our understanding of the regulation of both the cellular levels of DHLA, AA, and EPA, and their availability for eicosanoid synthesis. In addition, these findings provide a context for the effective use of these fatty acids in dietary therapies directed at modulation of eicosanoid production.

8,11,14-Eicosatrienoic Acid↗

The medical appointment scheduler.

In order to enhance our understanding of how to best improve patient care, it was necessary to initially identify key questions that patients ask most frequently by recording actual calls made by home hemodialysis patients to a dialysis clinic over a three-month period. From an initial analysis of the recorded conversations, one of the most frequent reasons for patient calls was for scheduling concerns. Since the use of automated systems often enable a quicker response to patients' needs and alleviate time demands on the personnel that have to answer these calls, an automated scheduling system was designed and implemented to address this concern. The SCHEDULER is a mixed-initiative spoken dialogue system that allows a patient to schedule an appointment with a provider over the telephone. The system was implemented using SPEECHBUILDER, a utility developed by the Spoken Language System group at M.I.T. that helps automatically configure human language technology servers to create a new conversational system. We describe the system architecture, general considerations in the design, and a preliminary evaluation of the system.

Appointments and Schedules↗

Swainsonine treatment accelerates intracellular transport and secretion of glycoproteins in human hepatoma cells.

We are interested in determining whether carbohydrates are important regulatory determinants in the intracellular transport and secretion of glycoproteins. In the present study, we have used swainsonine, an indolizidine alkaloid, to modify the structure of N-glycosidically linked complex oligosaccharides. By inhibiting Golgi mannosidase II, swainsonine prevents the trimming of GlcNAc(Man)5(GlcNAc)2 to GlcNAc-(Man)3(GlcNAc)2, resulting in the formation of hybrid-type oligosaccharides. We find, from pulse-chase experiments using [35S]methionine and immunoprecipitation of individual proteins from culture media, that swainsonine treatment (1 microgram/ml) accelerated the secretion of glycoproteins (transferrin, ceruloplasmin, alpha 2-macroglobulin, and alpha 1-antitrypsin) by decreasing the lag period by 10-15 min relative to untreated cultures. The enhanced secretion was specific for glycoproteins since the secretion of albumin, a nonglycoprotein, was unaffected. When alpha 1-antitrypsin was immunoprecipitated from the cell lysates, sodium dodecyl sulfate-polyacrylamide gel electrophoresis fluorographic analysis demonstrated that the conversion of the high-mannose precursor to the hybrid form in swainsonine-treated cells occurred more rapidly (by about 10 min) than the conversion to the complex form in control cells. Since both the hybrid and complex forms of alpha 1-antitrypsin are terminally sialylated by sialyltransferase in the trans-Golgi, these results suggest that swainsonine-modified glycoproteins traverse the Golgi more rapidly than their normal counterparts. Therefore, accelerated transport within this organelle may account for the decreased lag period of glycoprotein secretion in the swainsonine-treated cultures.

Alkaloids↗

Psychiatrists choosing psychoanalytic training at mid-career.

At one institute 48 percent of physician candidates doing class-work are over 40. This percentage has increased over the past decade, perhaps reflecting new economic constraints and the increased proportion of women candidates. A review of the first training analysis, Freud's, and conversations with some present day candidates indicate that choosing training at mid-career can address specific adult developmental issues, including the "race against time," needs for increased structuring of family life and of creative work and shifts from physical to intellectual play and from being a mentee to mentorship.

Adult↗

[Clinical effects of Juzendaiho-to on immunologic and fatty metabolic states in postoperative patients with gastrointestinal cancer].

Juzen-daiho-to is one of the Chinese traditional medicines which is usually applied with patients suffering from anemia or chronic exhaustive disease. Twenty-three patients after gastrectomy and 16 patients after colectomy were studied for NK cell activity, blastogenesis by PHA, several T-lymphocyte subsets, serum triglyceride and serum lipo-protein before drug administration at one, three, six, nine months and one year after the start of drug administration respectively. A remarkable elevation in NK cell activity was noted 3 and 6 months after the drug administration. Statistical analysis shows a significant converse correlation between NK cell activity and lipo-protein value in the group given Juzendaiho-to.

Animals↗

Perceived variability and symbol use: a common language-cognition interface in children and chimpanzees (Pan troglodytes).

Analysis of two chimpanzees' conversations with their teacher during a tool-use training task demonstrated that chimps use lexigrams, a humanly devised visual symbol system, selectively to encode perceived variability; that is, they generally used their symbols to differentiate alternative possibilities or to represent change or novelty in a situation. In contrast, they tended to leave unsaid what was unchanging, repetitive, or the unique possibility in a situation. Perceived variability influenced not only which symbols were selected but also utterance length: A single dimension of variability in a situation leads to single-lexigram utterances; multiple dimensions are associated with multi-lexigram utterances. This pattern of results indicates that the absence of formal grammatical structure in chimp language does not imply that utterances beyond one word in length are either rote strings or imitations. The chimps' tendency to mention the variable while leaving the constant or redundant unsaid is, moreover, strong support for the position that their use of a humanly devised symbol system is more than a series of conditioned responses.

Animals↗

Identification of arachidonate epoxides/diols by capillary chromatography-mass spectrometry.

The identification of epoxide regioisomers of arachidonic acid (EETs) as methyl esters is difficult because they coelute during gas chromatography and possess similar mass spectra. In the present study, EETs and their hydrolysis products, dihydroxyeicosatrienoic acids (DHETs), were analyzed as pentafluorobenzyl ester derivatives and their properties were compared to other esters. The four EET regioisomers were not resolved by gas chromatography as pentafluorobenzyl, trimethylsilyl, t-butyldimethylsilyl, or methyl esters. However, after being hydrolyzed to DHETs, three of the four regioisomers were resolved as (bis)-t-butyldimethylsilyl ether, pentafluorobenzyl esters. The fourth regioisomer (5,6-DHET) was resolved after being converted to a delta-lactone. Thus, the EETs could be resolved by capillary gas chromatography once converted to DHETs. Pentafluorobenzyl esters of both EETs and DHETs (15-40 ng) provided diagnostic spectra when analyzed by electron ionization mass spectrometry. The mass spectral interpretations that indicated epoxide and diol positions were validated using synthesized EET/DHET [17,17,18,18-d4, 5,6,8,9,11,12,14,15 d8] standards. Lesser amounts of DHETs (5-150 fg) also indicated molecular weights when analyzed in the negative-ion chemical-ionization mode. In summary, EETs in nanogram quantities were identified as pentafluorobenzyl esters using electron ionization mass spectrometry. EETs in femtogram-to-picogram quantities were also identified after conversion to DHETs and analysis by gas chromatography-mass spectrometry in the negative ion-chemical ionization mode.

Arachidonic Acid↗

Efficacy of agents for pharmacologic conversion of atrial fibrillation and subsequent maintenance of sinus rhythm: a meta-analysis of clinical trials.

CONTEXT: Physicians have little evidentiary guidance for pharmacologic agent selection for atrial fibrillation (AF). OBJECTIVE: To assess antiarrhythmic agent efficacy for AF conversion and subsequent maintenance of sinus rhythm (MSR). DATA SOURCE: We searched the clinical trial database of the Cochrane Collaboration and MEDLINE encompassing literature from 1948 to May 1998. STUDY SELECTION: We selected 36 (28%) articles eligible as randomized trials of nonpostoperative AF conversion or MSR in adults. DATA EXTRACTION: Study quality; rates of conversion, MSR, and adverse events were extracted. DATA SYNTHESIS: Compared with control treatment (placebo, verapamil, diltiazem, or digoxin), the odds ratio (OR) for conversion was greatest for ibutilide/dofetilide (OR=29.1; 95% confidence interval [CI], 9.8-86.1) and flecainide (OR=24.7; 95% CI, 9.0-68.3). Less strong but conclusive evidence existed for propafenone (OR=4.6; 95% CI, 2.6-8.2). Quinidine (OR=2.9; 95% CI, 1.2-7.0) had moderate evidence of efficacy for conversion. Disopyramide (OR=7.0; 95% CI, 0.3-153.0) and amiodarone (OR=5.7; 95% CI, 1.0-33.4) had suggestive evidence of efficacy. Sotalol (OR=0.4; 95% CI, 0.0-3.0) had suggestive evidence of negative efficacy. For MSR, strong evidence of efficacy existed for quinidine (OR=4.1; 95% CI, 2.5-6.7), disopyramide (OR=3.4; CI, 1.6-7.1), flecainide (OR=3.1; 95% CI, 1.5-6.2), propafenone (OR=3.7; 95% CI, 2.4-5.7), and sotalol (OR=7.1; 95% CI, 3.8-13.4). The only amiodarone data, from comparison with disopyramide, provided moderate evidence of efficacy for MSR. No trial evaluated procainamide. Direct agent comparisons and adverse event data were limited. CONCLUSIONS: Although multiple antiarrhythmic agents had strong evidence of efficacy compared with control treatment for MSR, ibutilide/dofetilide and flecainide had particularly strong evidence of efficacy compared with control treatment for AF conversion. There is sparse and inconclusive evidence on direct agent comparisons and adverse event rates. Obtaining information regarding these relative efficacies should be a research priority.

Aged↗

Evolution of proteinuria after conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) in renal transplant patients: a multicenter study.

Conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) has become an option in patients with chronic allograft nephropathy or other conditions. However, in some cases an increase of proteinuria has been reported after such therapeutic intervention. The aim of this study was to characterize the clinical course of this so far unexplained proteinuria after conversion. We performed a retrospective analysis evaluating 94 renal transplant patients from various Spanish centers. Proteinuria (629 determinations) and clinical developments were analyzed between 6 months before and 6 months after conversion. Patients were divided into three groups according to mean proteinuria before conversion (group A: <300 mg/d; group B: 300 to 2000 mg/d; and group C: >2 g/d). The mean proteinuria level was 1.69 g/24 h (n = 312 determinations) before and 2.36 g/24 h after conversion (n = 317 determinations; P = .006), which corresponds to an overall increase of 25% (1.55 to 1.69 g/24 h considering only determinations of 1 month before and 1 month after conversion; P = NS). We could not detect any clear correlation between proteinuria and serum creatinine nor between changes of proteinuria and changes of serum creatinine. A variance analysis for repeated measures showed an increase in proteinuria compared to the preconversion values (P = .003), and when the three groups of preconversion proteinuria were evaluated separately it could be observed that this change in the evolution of proteinuria was almost completely dependent of an increase in the group C (preconversion proteinuria greater than 2 g/d; P = .03), whereas in the other two groups changes were almost irrelevant. Finally, the switch to SRL in renal transplant recipients is followed by an increase in the level of proteinuria predominantly dependent of an increase in patients with high levels of preconversion proteinuria, whereas it seems to be irrelevant in patients without or with light or moderate proteinuria. These results suggest that this might not be a direct effect of SRL.

Calcineurin Inhibitors↗

Sirolimus conversion after liver transplantation: improvement in measured glomerular filtration rate after 2 years.

METHODS: We reviewed our prospectively maintained database of 2005 liver transplantations. Therapy was either started de novo or converted from calcineurin inhibitors (CNIs) to sirolimus as the main immunosuppressive agent for nephrotoxicity or rejection. Glomerular filtration rate (GFR) was determined with iodine 125-labeled sodium isthalamate (Glofil-125), and serum creatinine concentration was obtained before and 3 months after transplantation, and yearly in both groups. Sirolimus levels were 10 to 15 ng/mL in patients at less than 3 months after transplantations and 5 to 10 ng/mL in the remaining patients. All patients received mycophenolate mofetil as maintenance therapy. RESULTS: Data for 29 patients in the de novo group and 35 in the conversion group were reviewed. Patients in the de novo group demonstrated an acute cellular rejection rate of 17.2%, 40% of which were steroid resistant. In this group, 48.2% discontinuation of sirolimus was necessary because of adverse effects. Patients in the conversion group demonstrated an acute cellular rejection rate of 2.8% and a 34.3% rate of sirolimus discontinuation. Seventeen (56.7%) patients at 1 year and 8 (44.4%) patients at 2 years demonstrated continued improvement in GFR. In the conversion group, case-control analysis did not demonstrate a significant difference in GFR and serum creatinine concentration (P > .05) at 1 and 2 years after conversion. At the time of review, no patients in the conversion group required hemodialysis. CONCLUSIONS: Conversion to sirolimus therapy is an effective strategy in improving renal function in patients with CNI-induced nephrotoxicity and can be done without increased rejection. Most of our patients (65.7%) tolerated sirolimus conversion. Of these, 56.7% and 44.4% demonstrated continued increase in GFR with the CNI-free regimen at 1 and 2 years, respectively. Long-term, large-population, prospective, randomized, controlled studies should further validate these results.

Creatinine↗