Algometry to measure pain threshold in the horse's back - An in vivo and in vitro study

Abstract Background The aim of this study was to provide information on algometric transmission of pressure through the dorsal thoracolumbar tissues of the equine back. Using a commercially available algometer, measurements were carried out with six different tips (hemispheric and cylindrical surfaces, contact areas 0.5 cm2, 1 cm2, and 2 cm2). In nine live horses the threshold of pressure that lead to any reaction was documented. In postmortem specimens of five euthanized horses the transmission of algometer pressure onto a pressure sensor placed underneath the dorsal thoracolumbar tissues at the level of the ribs or the transverse lumbar processes respectively was measured. Results Algometer tips with a contact area of 1 cm2 led to widely similar results irrespective of the surface shape; these measurements also had the lowest variance. Contact areas of 0.5 cm2 resulted in a lower pressure threshold, and those of 2 cm2 resulted in a higher pressure threshold. The hemispheric shape of the contact area resulted in a higher pressure threshold, than the cylindrical contact area. Compared to the thoracic region, a significantly higher pressure threshold was found in the lumbar region in the live horses. This result corresponds to the increased tissue thickness in the lumbar region compared to the thoracic region, also documented as less pressure transmission in the lumbar region on the in vitro specimens. Conclusions Algometry is an easily practicable and well tolerated method to quantify pain but it is important to consider the many factors influencing the results obtained

Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.

Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy. Incoming peptides are recognized according to the global stability of the final pMHC-I product and anneal in a native-like conformation to be edited by TAPBPR. Our results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. These results suggest a similar mechanism for the function of tapasin in the peptide-loading complex

N-acetylcysteine does not prevent contrast-induced nephropathy after cardiac catheterization in patients with diabetes mellitus and chronic kidney disease: a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) constitute to be a high-risk population for the development of contrast-induced nephropathy (CIN), in which the incidence of CIN is estimated to be as high as 50%. We performed this trial to assess the efficacy of <it>N</it>-acetylcysteine (NAC) in the prevention of this complication.</p> <p>Methods</p> <p>In a prospective, double-blind, placebo controlled, randomized clinical trial, we studied 90 patients undergoing elective diagnostic coronary angiography with DM and CKD (serum creatinine ≥ 1.5 mg/dL for men and ≥ 1.4 mg/dL for women). The patients were randomly assigned to receive either oral NAC (600 mg BID, starting 24 h before the procedure) or placebo, in adjunct to hydration. Serum creatinine was measured prior to and 48 h after coronary angiography. The primary end-point was the occurrence of CIN, defined as an increase in serum creatinine ≥ 0.5 mg/dL (44.2 μmol/L) or ≥ 25% above baseline at 48 h after exposure to contrast medium.</p> <p>Results</p> <p>Complete data on the outcomes were available on 87 patients, 45 of whom had received NAC. There were no significant differences between the NAC and placebo groups in baseline characteristics, amount of hydration, or type and volume of contrast used, except in gender (male/female, 20/25 and 34/11, respectively; P = 0.005) and the use of statins (62.2% and 37.8%, respectively; P = 0.034). CIN occurred in 5 out of 45 (11.1%) patients in the NAC group and 6 out of 42 (14.3%) patients in the placebo group (P = 0.656).</p> <p>Conclusion</p> <p>There was no detectable benefit for the prophylactic administration of oral NAC over an aggressive hydration protocol in patients with DM and CKD.</p> <p>Trial registration</p> <p>NCT00808795</p

Septic AKI in ICU patients. diagnosis, pathophysiology, and treatment type, dosing, and timing: a comprehensive review of recent and future developments

Evidence is accumulating showing that septic acute kidney injury (AKI) is different from non-septic AKI. Specifically, a large body of research points to apoptotic processes underlying septic AKI. Unravelling the complex and intertwined apoptotic and immuno-inflammatory pathways at the cellular level will undoubtedly create new and exciting perspectives for the future development (e.g., caspase inhibition) or refinement (specific vasopressor use) of therapeutic strategies. Shock complicating sepsis may cause more AKI but also will render treatment of this condition in an hemodynamically unstable patient more difficult. Expert opinion, along with the aggregated results of two recent large randomized trials, favors continuous renal replacement therapy (CRRT) as preferential treatment for septic AKI (hemodynamically unstable). It is suggested that this approach might decrease the need for subsequent chronic dialysis. Large-scale introduction of citrate as an anticoagulant most likely will change CRRT management in intensive care units (ICU), because it not only significantly increases filter lifespan but also better preserves filter porosity. A possible role of citrate in reducing mortality and morbidity, mainly in surgical ICU patients, remains to be proven. Also, citrate administration in the predilution mode appears to be safe and exempt of relevant side effects, yet still requires rigorous monitoring. Current consensus exists about using a CRRT dose of 25 ml/kg/h in non-septic AKI. However, because patients should not be undertreated, this implies that doses as high as 30 to 35 ml/kg/h must be prescribed to account for eventual treatment interruptions. Awaiting results from large, ongoing trials, 35 ml/kg/h should remain the standard dose in septic AKI, particularly when shock is present. To date, exact timing of CRRT is not well defined. A widely accepted composite definition of timing is needed before an appropriate study challenging this major issue can be launched

The challenge of admitting the very elderly to intensive care

The aging of the population has increased the demand for healthcare resources. The number of patients aged 80 years and older admitted to the intensive care unit (ICU) increased during the past decade, as has the intensity of care for such patients. Yet, many physicians remain reluctant to admit the oldest, arguing a "squandering" of societal resources, that ICU care could be deleterious, or that ICU care may not actually be what the patient or family wants in this instance. Other ICU physicians are strong advocates for admission of a selected elderly population. These discrepant opinions may partly be explained by the current lack of validated criteria to select accurately the patients (of any age) who will benefit most from ICU hospitalization. This review describes the epidemiology of the elderly aged 80 years and older admitted in the ICU, their long-term outcomes, and to discuss some of the solutions to cope with the burden of an aging population receiving acute care hospitalization