Levels of Speech Usage: A Self-Report Scale for Describing How People Use Speech

People use speech in a variety of ways to fulfill life roles and responsibilities. Documenting speech usage is critical in clinical work to plan relevant intervention goals for individual clients, and in clinical research to better describe participant characteristics. A few voice-use classification scales exist; however, they are limited in scope (e.g., focus almost exclusively on occupation) and in applicability beyond voice-disordered populations. The Levels of Speech Usage is a self-report categorical rating scale intended for use with adults across a wide range of communication disorders and life situations. This article presents data from the initial analysis of this scale in a sample of 200 people with spasmodic dysphonia (SD). Speech usage was significantly associated with age, education level, and work status (full time, part time, no paid work). Speech usage was not significantly associated with gender, SD duration, self-rating of voice, treatment status, presence of other medical conditions, Voice Handicap Index, or a measure of communicative participation. Further research is needed to explore the function of this scale in other populations.     

First documented rhythm and clinical outcome from in-hospital cardiac arrest among children and adults

Context  Cardiac arrests in adults are often due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), which are associated with better outcomes than asystole or pulseless electrical activity (PEA). Cardiac arrests in children are typically asystole or PEA. Objective  To test the hypothesis that children have relatively fewer in-hospital cardiac arrests associated with VF or pulseless VT compared with adults and, therefore, worse survival outcomes. Design, Setting, and Patients  A prospective observational study from a multicenter registry (National Registry of Cardiopulmonary Resuscitation) of cardiac arrests in 253 US and Canadian hospitals between January 1, 2000, and March 30, 2004. A total of 36 902 adults (18 years) and 880 children (<18 years) with pulseless cardiac arrests requiring chest compressions, defibrillation, or both were assessed. Cardiac arrests occurring in the delivery department, neonatal intensive care unit, and in the out-of-hospital setting were excluded. Main Outcome Measure  Survival to hospital discharge. Results  The rate of survival to hospital discharge following pulseless cardiac arrest was higher in children than adults (27% [236/880] vs 18% [6485/36 902]; adjusted odds ratio [OR], 2.29; 95% confidence interval [CI], 1.95-2.68). Of these survivors, 65% (154/236) of children and 73% (4737/6485) of adults had good neurological outcome. The prevalence of VF or pulseless VT as the first documented pulseless rhythm was 14% (120/880) in children and 23% (8361/36 902) in adults (OR, 0.54; 95% CI, 0.44-0.65; P<.001). The prevalence of asystole was 40% (350) in children and 35% (13 024) in adults (OR, 1.20; 95% CI, 1.10-1.40; P = .006), whereas the prevalence of PEA was 24% (213) in children and 32% (11 963) in adults (OR, 0.67; 95% CI, 0.57-0.78; P<.001). After adjustment for differences in preexisting conditions, interventions in place at time of arrest, witnessed and/or monitored status, time to defibrillation of VF or pulseless VT, intensive care unit location of arrest, and duration of cardiopulmonary resuscitation, only first documented pulseless arrest rhythm remained significantly associated with differential survival to discharge (24% [135/563] in children vs 11% [2719/24 987] in adults with asystole and PEA; adjusted OR, 2.73; 95% CI, 2.23-3.32). Conclusions  In this multicenter registry of in-hospital cardiac arrest, the first documented pulseless arrest rhythm was typically asystole or PEA in both children and adults. Because of better survival after asystole and PEA, children had better outcomes than adults despite fewer cardiac arrests due to VF or pulseless VT.      

Fact or fiction? A critique of the National Aboriginal and Torres Strait Islander Social Survey 2002

The ability of policy makers, practitioners and the broader public to respond appropriately in reducing the harms caused by alcohol misuse depends in large part on our understanding of the nature of the problem. In the case of consumption patterns and associated harms among indigenous minority peoples—in Australia and elsewhere—such an understanding is often difficult to achieve. There are a host of reasons for this including cultural differences between indigenous peoples and the broader populations within which they are located, cultural heterogeneity among indigenous peoples themselves, political and economic disadvantages which exacerbate misuse and its effects, methodological difficulties in the appropriate design of data collection instruments, sampling issues and the issues in the interpretation of data. All these difficulties mean that we need to subject any studies of substance misuse among indigenous peoples to a high level of scrutiny. This is particularly the case when such studies are conducted by organisations that are generally regarded as 'authoritative' sources of information. Chikritzhs & Brady have done this in the case of the National Aboriginal and Torres Strait Islander Social Survey 2002, conducted by the Australian Bureau of Statistics. In their review of this and other surveys, they demonstrate that to produce valid information about indigenous alcohol misuse, as well as having the skills to conduct broad population surveys, it is necessary to have an understanding of both methods of collecting data on alcohol consumption and Indigenous cultures themselves.

GuestEditor:DennisGray     

Absolute oral bioavailability of traxoprodil in cytochrome P450 2D6 extensive and poor metabolisers

BACKGROUND: Traxoprodil, a substituted 4-phenylpiperidine, is an N-methyl-D-aspartate (NMDA) receptor antagonist that is selective for receptors containing the NR2B subunit. In vivo and in vitro studies examining the disposition of traxoprodil have demonstrated that it is mainly metabolised by cytochrome P450 (CYP) 2D6, a major drug-metabolising enzyme that exhibits a genetic polymorphism. OBJECTIVE: To assess the single-dose absolute oral bioavailability of traxoprodil in healthy male volunteers phenotyped as either CYP2D6 extensive or poor metabolisers. METHODS: This was an open-label, three-way crossover study. Traxoprodil was administered as a single dose orally in solution of 50, 100 and 300mg and intravenously as a constant rate 2-hour infusion of 50 and 100mg. CYP2D6 phenotype was assigned following single-dose dextromethorphan administration. RESULTS: In poor metabolisers (n = 6), oral bioavailability was approximately 80% and was consistent with a liver extraction ratio of approximately 20% (plasma clearance of approximately 4 mL/min/kg) indicating near complete absorption. Following intravenous administration, the mean volume of distribution at steady state (V(ss)) was moderate (approximately 6.5 L/kg) and the mean elimination half-life (t((1/2))) was approximately 20 hours. Following oral administration the mean maximum plasma concentration (C(max)) and area under the plasma concentration-time curve from time zero to infinity (AUC(infinity)) increased approximately proportionally with dose. In extensive metabolisers (n = 11), oral bioavailability was dose-dependent and nonlinear. At the 100mg dose, the absolute oral bioavailability was approximately 39.5%. Overall, the oral bioavailability ranged from 22.8% to 62.1% and its estimation was confounded by large differences in plasma concentrations at oral doses without equivalent intravenous doses. Following intravenous administration, plasma clearance was high (approximately 27 mL/min/kg), the V(ss) was moderate (approximately 4 L/Kg) and the t((1/2)) was approximately 2-4 hours. Following oral administration the C(max) and AUC(infinity) increased more than proportionally with dose. Apparent oral clearance decreased with increasing oral dose. However, t((1/2)) was approximately the same at all doses (approximately 4 hours). CONCLUSION: The pharmacokinetics of traxoprodil were quite different in the two phenotypes. In extensive metabolisers, the oral bioavailability was nonlinear and dose-dependent, while in poor metabolisers, oral bioavailability appeared to be linear and dose-independent. Based on the pharmacokinetics in extensive and poor metabolisers, the nonlinear oral bioavailability in extensive metabolisers may be attributed to saturation of hepatic first-pass CYP2D6 metabolism. Thus, at a high oral dose, the impact of CYP2D6 metabolism on traxoprodil pharmacokinetics is minimal.     

Evaluation of basic amphipathic peptides for cellular delivery of antisense peptide nucleic acids

Cellular permeation peptides have been used successfully for the delivery of a variety of cargoes across cellular membranes, including large hydrophilic biomolecules such as proteins, oligonucleotides, or plasmid DNA. For the present work, a series of short amphipathic peptides was designed to elucidate the structural requirements for efficient and nontoxic delivery of peptide nucleic acids (PNAs). On the basis of an idealized alpha-helical structure, the helical parameters were modulated systematically to yield peptides within a certain range of hydrophobicity and amphipathicity. The corresponding PNA conjugates were synthesized and characterized in terms of secondary structure, enzymatic stability, and antisense activity. The study revealed correlations between the physicochemical and biophysical properties of the conjugates and their biological activity and led to the development of potent peptide vectors for the cellular delivery of antisense PNAs. Two representative compounds were radiolabeled and evaluated for their biodistribution in healthy mice.     

Tumor-induced thymic involution via inhibition of IL-7R alpha and its JAK-STAT signaling pathway: protection by black tea

Down-regulation of cell-mediated immune functions occurring at late stages of cancer may be related to the thymic involution since thymus is the major site of T cell maturation, proliferation, and differentiation. We found that in Ehrlich's ascites carcinoma (EAC)-bearing mice there was profound depletion of CD4+ and CD8+ cells in peripheral blood with severely damaged thymus on 21st day of tumor inoculation. However, treatment with black tea at an antitumor dose of 2.5% significantly reduced such depletion and protected the thymus considerably from tumor onslaught. A search for the underlying mechanism revealed EAC-induced IL-7Ralpha down-regulation, inhibition of JAK3 and STAT5 phosphorylation, and decrease in Bcl-2/Bax ratio in thymocytes that finally led to thymocyte apoptosis in one hand and T cell maturation block on the other. Interestingly, black tea treatment prevented IL-7Ralpha down-regulation and protected the signaling cascade through JAK-STAT thereby inhibiting tumor-induced thymic apoptosis and ensuring proper functioning of this organ in tumor-bearing host.