Continuous monitoring of the bronchial epithelial lining fluid by microdialysis

<p>Abstract</p> <p>Background</p> <p>Contents of the epithelial lining fluid (ELF) of the bronchi are of central interest in lung diseases, acute lung injury and pharmacology. The most commonly used technique broncheoalveolar lavage is invasive and may cause lung injury. Microdialysis (MD) is a method for continuous sampling of extracellular molecules in the immediate surroundings of the catheter. Urea is used as an endogenous marker of dilution in samples collected from the ELF. The aim of this study was to evaluate bronchial MD as a continuous monitor of the ELF.</p> <p>Methods</p> <p>Microdialysis catheters were introduced into the right main stem bronchus and into the right subclavian artery of five anesthetized and normoventilated pigs. The flowrate was 2 μl/min and the sampling interval was 60 minutes. Lactate and fluorescein-isothiocyanate-dextran 4 kDa (FD-4) infusions were performed to obtain two levels of steady-state concentrations in blood. Accuracy was defined as [bronchial-MD] divided by [arterial-MD] in percent. Data presented as mean ± 95 percent confidence interval.</p> <p>Results</p> <p>The accuracy of bronchial MD was calculated with and without correction by the arteriobronchial urea gradient. The arteriobronchial lactate gradient was 1.2 ± 0.1 and FD-4 gradient was 4.0 ± 1.2. Accuracy of bronchial MD with a continuous lactate infusion was mean 25.5% (range 5.7–59.6%) with a coefficient of variation (CV) of 62.6%. With correction by the arteriobronchial urea gradient accuracy was mean 79.0% (57.3–108.1%) with a CV of 17.0%.</p> <p>Conclusion</p> <p>Urea as a marker of catheter functioning enhances bronchial MD and makes it useful for monitoring substantial changes in the composition of the ELF.</p

Pharmacist provision of primary health care: a modified Delphi validation of pharmacists' competencies

<p>Abstract</p> <p>Background</p> <p>Pharmacists have expanded their roles and responsibilities as a result of primary health care reform. There is currently no consensus on the core competencies for pharmacists working in these evolving practices. The aim of this study was to develop and validate competencies for pharmacists' effective performance in these roles, and in so doing, document the perceived contribution of pharmacists providing collaborative primary health care services.</p> <p>Methods</p> <p>Using a modified Delphi process including assessing perception of the frequency and criticality of performing tasks, we validated competencies important to primary health care pharmacists practising across Canada.</p> <p>Results</p> <p>Ten key informants contributed to competency drafting; thirty-three expert pharmacists replied to a second round survey. The final primary health care pharmacist competencies consisted of 34 elements and 153 sub-elements organized in seven CanMeds-based domains. Highest importance rankings were allocated to the domains of care provider and professional, followed by communicator and collaborator, with the lower importance rankings relatively equally distributed across the manager, advocate and scholar domains.</p> <p>Conclusions</p> <p>Expert pharmacists working in primary health care estimated their most important responsibilities to be related to direct patient care. Competencies that underlie and are required for successful fulfillment of these patient care responsibilities, such as those related to communication, collaboration and professionalism were also highly ranked. These ranked competencies can be used to help pharmacists understand their potential roles in these evolving practices, to help other health care professionals learn about pharmacists' contributions to primary health care, to establish standards and performance indicators, and to prioritize supports and education to maximize effectiveness in this role.</p

Milton, Leibniz, and the Measure of Motion

Milton’s description of the “high capital / Of Satan and his peers,” the aptly named Pan-daemonium, leads to a memorable account of its architect’s expulsion from heaven: Men called him Mulciber; and how he fell From heaven, they fabled, thrown by angry Jove Sheer o’er the Crystal Battlements; from morn To noon he fell, from noon to dewy eve, A summer’s day; and with the setting Sun Dropped from the zenith like a falling Star, On Lemnos the Aegaean Isle: thus they relate, Erring; for he with this rebellious rout Fell long before; nor aught availed him now To have built in heaven high towers; nor did he scape By all his engines, but was headlong sent With his industrious crew to build in hell. (I: 740-751) Here, as often in Milton’s epic, time provides the measure of motion – recall, for instance, the war in heaven, which concludes with the anarchic descent of the defeated angels: “Nine days they fell; confounded Chaos roared, / And felt tenfold confusion in their fall” (VI: 871-72). Elsewhere space provides the measure of both time and stasis, as in an earlier, parallel description of the aftermath of this defeat: “Nine times the space that measures day and night / To mortal men, he with his horrid crew / Lay vanquished (I: 50-52). In these examples, falling – a continuous change in location over a duration – is measured by time’s succession, whereas the duration of immobility is imagined as spatial extension,the “space” that the fallen “lay vanquished.” Such shifting articulations of time and spaceare not surprising, since at stake are precisely motion and stasis, both of which necessarily demand relating the spatial to the temporal

05205.q.FInal

Patients with resistance to thyroid hormone (RTH) exhibit elevated thyroid hormone levels and inappropriate thyrotropin (thyroid-stimulating hormone, or TSH) production. The molecular basis of this disorder resides in the dominant inhibition of endogenous thyroid hormone receptors (TRs) by a mutant receptor. To determine the relative contributions of pituitary versus hypothalamic resistance to the dysregulated production of thyroid hormone in these patients, we developed a transgenic mouse model with pituitary-specific expression of a mutant TR (∆337T). The equivalent mutation in humans is associated with severe generalized RTH. Transgenic mice developed profound pituitary resistance to thyroid hormone, as demonstrated by markedly elevated baseline and non-triodothyronine (T 3 )-suppressible serum TSH and pituitary TSH-β mRNA. Serum thyroxine (T 4 ) levels were only marginally elevated in transgenic mice and thyrotropin-releasing hormone (TRH) gene expression in the paraventricular hypothalamus was downregulated. After TRH administration, T 4 concentrations increased markedly in transgenic, but not in wild-type mice. Transgenic mice rendered hypothyroid exhibited a TSH response that was only 30% of the response observed in wild-type animals. These findings indicate that pituitary expression of this mutant TR impairs both T 3 -mediated suppression and T 3 -independent activation of TSH production in vivo. The discordance between basal TSH and T 4 levels and the reversal with TRH administration demonstrates that resistance at the level of both the thyrotroph and the hypothalamic TRH neurons are required to elevate thyroid hormone levels in patients with RTH

Deprescribing interventions in primary health care mapped to the Behaviour Change Wheel: A scoping review

Deprescribing interventions in primary health care mapped to the Behaviour Change Wheel: A scoping revie