We monitored, by the Holter method, 23 clinically stable maintenance hemodialysis patients for 5 +/- (SEM) 2 hours before hemodialysis, 5.0 +/- 0.5 hours during hemodialysis, and 13 +/- 3 hours after hemodialysis. Of 23 patients, 9 (39%) had unexpected frequent or complex ventricular arrhythmias recorded and after hemodialysis with a potassium dialysate bath concentration of 2.0 mEq/liter. Patients with ventricular arrhythmias were more likely to be using digoxin (8/9 vs. 1/4) and to have evidence of left ventricular hypertrophy (9/9 vs. 7/4 than were those patients without arrhythmias. Of these 9 patients with arrhythmias, 6 underwent repeat Holter monitoring during multiple dialysate protocols. Of the 6 patients, 4 had a significant reduction in the frequency of ventricular ectopy when a dialysate of 3.5 mEq/liter potassium was used (P < 0.05), but of these 6, 3 still had complex arrhythmias. The use, however, of a 3.5 mEq/liter potassium dialysate plus the administration of a 400-mg dose of quinidine sulfate orally 45 min prior to hemodialysis was successful in reducing ventricular ectopic frequency and complexity in all the patients studied. Conclusion. Maintenance hemodialysis patient using digoxin and with left ventricular hypertrophy have an unexpectdly high indicence of occult, potentoial serious, ventricular arrhythmias during and after hemodialysis, revealed by Holter monitoring. There is preliminary evidence that a low-potassium bath concentration may play a role in predisoposing patients to these arrhythmias. Further prospective studies with largaer number of patients will be needed, however, to evaluate the significance of these findings.
Recent technological innovations have facilitated widespread illegal downloading of recorded music. While this points towards a decreased willingness to pay for music, the increase in the popularity of live music suggests otherwise. This is especially so when taking into account the rising cost of concert tickets, likely the result of reduced recorded music revenues. In the present study, a consideration of the unique motivations of why music fans decide on whether or not to attend live concerts is of interest. Drawing from a sample of 249 participants (55.02% female) with a mean age of 26.49, an open-ended questionnaire was analysed thematically with four key themes defined: Experience, Engagement, Novelty and Practical. The results highlight that participants want to "be there", to be a part of something unique and special, sharing the experience with likeminded others. Other social dimensions such as the use of live music events as a means to demonstrate fan worship were also found. The unknown, novel aspects of live music were key motivators, such as hearing new material and watching support bands. Notably, price was not a contributing factor when choosing to attend a concert, suggesting that live music offers fans something special that they are more than willing to pay for.
Cyclosporin A is a cyclic peptide believed to exist as multiple conformers in aqueous solution. Two major conformations, distinguished by a single cis-trans isomerization and the presence of four either intramolecular or intermolecular hydrogen bonds, have been confirmed depending on whether CsA is characterized in organic solvents or bound in aqueous complex with cyclophilin. The relationship between CsA conformation and its ability to penetrate biological membranes is currently unknown. Using Caco-2 cell monolayers, we documented a remarkable increase (more than 2 orders of magnitude) in the membrane permeation of the peptide as temperature was increased from 5 to 37 degrees C. The solubility of CsA was 72 microM at 5 degrees C, but decreased by more than an order of magnitude at 37 degrees C. Moreover, CsA partitioned into non-hydrogen bond donating solvents linearly as a function of increasing temperature, suggestive of a significant conformational change. However, while NMR spectra of CsA confirmed the previously predicted presence of multiple conformers in aqueous solution, the equilibrium between the two major species was not affected by changes in temperature. These NMR data indicated that the observed temperature-dependent changes in the membrane permeability of CsA do not originate from changes in the peptide backbone conformation. Sedimentation equilibrium analysis revealed that CsA behaves in a highly nonideal manner over the temperature range tested. We interpret this behavior as a change in the hydration state with a smaller (or weaker) hydration shell surrounding the peptide at higher temperatures. Such a change would result in lower peptide desolvation energy, thereby promoting partitioning into cellular membranes. We contend that changes in membrane penetration result from alterations in the hydration state of CsA and are not related to the interconversion of the defined conformations.
Summary:Purpose: To determine whether repeat boluses of diazepam (DZP) lead to significant accumulation in the central nervous system and/or peripheral compartments, as repeat intravenous boluses of diazepam are commonly used in the treatment of status epilepticus (SE).Methods: In a rat model that permits simultaneous serum and cerebrospinal fluid (CSF) sampling, we characterized the pharmacokinetics of DZP and its metabolite, desmethyldiazepam, in CSF and blood using HPLC. DZP was administered by intraperitoneal injection as either a single dose (20 or 30 mg/ kg) or repeat doses (10 or 20 mgkg x 3, 1 h apart).Results: After a single intraperitoneal dose, DZP was rapidly absorbed with a time to maximum concentration of 10 min. The serum concentrations then declined biexponentially. DZP rapidly entered the CSF; the CSF to serum ratio reached equilibrium within 10 min, and was equivalent to the ratio of free to total serum concentration. Repeated DZP dosing resulted in a threefold decrease in volume of distribution and clearance (p < 0.001). This was reflected in the CSF concentration data; however, after the third dose, the ratio of CSF to serum concentration, also increased greatly, representing further persistence of DZP in the CSF compartment.Conclusions: Repeat dosing of DZP leads to substantial accumulation, and high, persistent serum and CSF concentrations, which may explain the toxic effects of repeat DZP dosing. Repeat dosing of DZP using a tapering protocol, however, may increase the effectiveness of DZP in treating SE by preventing relapses without substantially increasing toxicity.
Diazepam has been studied as an intravenous induction agent in intermittent and single doses. There is a delay of about 1 minute in onset of the soporific effect, and a great individual variation in response to the drug. Even with doses up to 0.8 mg/kg it was not possible to guarantee induction of anaesthesia. There was a remarkable absence of cardiovascular or other side effects, even from very large doses, and amnesia was also an outstanding feature. The eventual place of diazepam in anaesthesia will not be as a competitor with established induction agents. For many years barbiturates have had almost unchallenged supremacy in the field of intravenous anaesthesia, apart from some interest in a steroid (hydroxydione) and a phenoxyacetic amine (propanidid). More recently continental workers (Camplan and Espagno, 1964; Stovner and Endresen, 1966) have suggested that diazepam (Valium) might be useful in mis field. CH 3 /,O CI_J-N-=N CtH5 FIG. 1 Formula of diazepam (Valium).
With so many formats available for individuals to use to listen to music, the present research adopted a uses and gratifications approach to investigate why people prefer particular formats. Specifically, the present study considered six formats: physical, digital file, free-streaming, paid-for streaming, radio, and live music. A sample of 396 people (Mage = 34.53) completed an online survey, detailing the reasoning for their favorite format via a free-text response. Live music and digital files were the most popular formats. A thematic analysis of the uses and gratifications pertaining to each format highlighted how participants were attuned to the advantages (and disadvantages) of different formats, demonstrating an awareness of, and consideration relative to, rival formats. Findings suggest that choosing to listen to music across different formats may satisfy different needs and that people demonstrate an awareness of their preference relative to the other available options.
Addressing one of the principal lines of research on music piracy, the present study considers personality as predictive of favorable music piracy attitudes. Additionally, positive anti-piracy messages were explored as a potential deterrent. A total of 261 participants (45.60% male) with a mean age of 26.34 participated in an online questionnaire. Personality was measured using the 60-item version of the HEXACO PI-R (Lee & Ashton, 2004). The effects of positive verbal anti-piracy messages were measured using an existing research paradigm, with participants allocated to one of four conditions ("legal sales of music encourage future live performances", "legal sales of music allow fans greater access to exclusive content", "legal sales of music will incorporate charitable donations" and control) emphasizing different positive outcomes to legally purchasing recorded music. An original construct (AMP-12) measured attitudes towards music piracy. Personality was a significant predictor of piracy attitudes, with participants demonstrating propiracy attitudes scoring lower on honesty-humility and conscientiousness, and higher on openness. Condition did not affect attitudes towards music piracy. Further analysis on personality suggests that participants holding pro-piracy attitudes are less fair (using the HEXACO PI-R). Additional analyses show that both preference for digital music and being 24 or younger as predictive of pro-piracy attitudes. Building on related research, the study adds to the knowledge base on predictive factors and explores personality in some depth. Discussion centers on personality and more specifically the HEXACO PI-R factor of Fairness in defining useful areas for future research.
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