Systemic and splanchnic hemodynamics following hemorrhage and volume restitution with Haemaccel in portal hypertensive rats: The effect of propranolol

BACKGROUND AND AIMS: Recently, we found in a portal hypertensive rat model that hemorrhage and volume restitution with Haemaccel, a low viscosity plasma expander, induced an increase in cardiac output and portal venous inflow. The present study was conducted to evaluate whether pretreatment with propranolol will attenuate these hyperdynamic changes. METHODS: Portal hypertension was induced by portal vein constriction. Treatment was initiated 14--21 days later. Propranolol (30 mg/kg per day) or water were administered for 7 days via a gastric gavage. Under ketamine anesthesia, 18 h after the last given dose, blood was withdrawn at a constant rate of 0.3 mL/min for 15 min followed by a 15-min stabilization. Haemaccel was infused at the same rate and volume used for withdrawal. Hemodynamic measurements were performed after volume restitution in both groups by using radioactive microspheres. RESULTS: Eight rats were studied in each group. In the propranolol-treated animals, portal venous inflow was decreased (2.4 +/- 0.8 vs 3.8 +/- 0.7 mL/min per 100 g bodyweight; P < 0.01), while splanchnic arteriolar and porto-collateral resistance were increased (52.8 +/- 21.0 vs 32.8 +/- 13.0 and 6.0 +/- 1.4 vs 4.1 +/- 0.7 mmHg x min x 100 g bodyweight/mL; P < 0.05, respectively). Cardiac output, mean arterial pressure, heart rate, total peripheral resistance and portal pressure were not significantly different between the two groups. CONCLUSION: In this model, pretreatment with propranolol prevented the increase in portal venous inflow, which occurs following hemorrhage and volume restitution with Haemaccel. Although caution should be taken in extrapolating data from animal models to humans, our results suggest that volume replacement during a portal hypertensive-related bleeding episode may be safer in a patient treated with non-selective beta-adrenoreceptor antagonists.     

The role of executive function and attention in gait

Until recently, gait was generally viewed as a largely automated motor task, requiring minimal higher‐level cognitive input. Increasing evidence, however, links alterations in executive function and attention to gait disturbances. This review discusses the role of executive function and attention in healthy walking and gait disorders while summarizing the relevant, recent literature. We describe the variety of gait disorders that may be associated with different aspects of executive function, and discuss the changes occurring in executive function as a result of aging and disease as well the potential impact of these changes on gait. The attentional demands of gait are often tested using dual tasking methodologies. Relevant studies in healthy adults and patients are presented, as are the possible mechanisms responsible for the deterioration of gait during dual tasking. Lastly, we suggest how assessments of executive function and attention could be applied in the clinical setting as part of the process of identifying and understanding gait disorders and fall risk. © 2007 Movement Disorder Society     

The impact of educational intervention programs on pain management in a pediatric emergency department.

Management of pain and anxiety is an important part of patient care in the pediatric emergency department (ED). Even though it has improved significantly over the past few years, it is still suboptimal. The objective of this study was to evaluate the effect of informal and formal education on pain and anxiety management in the pediatric ED. Management of pain and anxiety was assessed by comparing the use of analgesics and sedatives during three phases: A) year 2000 (baseline), B) years 2001-2002 (informal teaching) and C) year 2004 (following a structured simulation-based training in pediatric sedation and analgesia). During period B there was a significant increase in the yearly use of eutectic mixture of local anesthetics (EMLA) (RR=2.63, CI 1.23-5.6), ibuprofen (RR=14.16, CI 8.73-22.98), midazolam (RR=1.68, CI 1.39-2.03) and nitrous oxide (N2O) in comparison with period A, with an additional increment of the first three medicines during period C. There was no change in the use of ketamine, morphine and meperidine during period B. Whereas, during period C, a significant increase in the use of ketamine and morphine was demonstrated (RR=24.56, CI 10.71-56.3 and RR=3.07, CI 2.12-4.44, respectively), while the use of meperidine (RR=0.68, CI 0.49-0.94) and N2O (RR=0.46, 95% CI 0.32-0.67) declined significantly. Educational interventions have a clear impact on pain and anxiety management demonstrated by the subsequent change in the use of sedatives and analgesics and should be provided to pediatric ED physicians. Informal teaching affected mainly the use of milder sedatives and analgesics, while formal structured training influenced the use of opioids and dissociative agents.     

Effective post-exposure protection against lethal orthopoxviruses infection by vaccinia immune globulin involves induction of adaptive immune response

The therapeutic potential of human vaccinia immunoglobulin (VIG) in orthopoxvirus infection was examined using two mouse models for human poxvirus, based on Ectromelia virus and Vaccinia Western Reserve (WR) respiratory infections. Despite the relatively fast clearance of human VIG from mice circulation, a single VIG injection protected immune-competent mice against both infections. Full protection against lethal Ectromelia virus infection was achieved by VIG injection up to one day post-exposure, and even injection of VIG two or three days post-infection conferred solid protection (60–80%). Nevertheless, VIG failed to protect VACV-WR challenged immune-deficient mice, even though repeated injections prolonged SCID mice survival. These results suggest the involvement of host immunity in protection. VIG provides the initial protective time-window allowing induction of the adaptive response required to achieve complete protection. Additionally, VIG can be administered in conjunction with active Vaccinia-Lister vaccination. Vaccine efficiency is not impaired, providing a non-prohibitive VIG dose is used. Thus, VIG can be used as a prophylactic measure against post-vaccinal complications but could also serve for post-exposure treatment against smallpox.     

Opposing effects of endothelin-1 on C-type natriuretic peptide actions in rat cardiomyocytes.

C-type natriuretic peptide (CNP) and Endothelin-1 are paracrine peptides with opposing vascular and mitogenic actions. In cardiac myocytes, CNP reduced contractility and induced accumulation of cyclic guanosine monophosphate (cGMP). Endothelin-1 caused an increase in contractile amplitude, abolished the negative inotropic effect of CNP, reduced the negative inotropic effect of a membrane permeable cGMP, and inhibited cGMP accumulation induced by CNP. We conclude that endothelin-1 abolishes the negative inotropic effect of CNP. This effect may be mediated by inhibition of the negative inotropic actions of cGMP as well as by reduction of cGMP levels.     

Reliability of the new freezing of gait questionnaire: Agreement between patients with Parkinson's disease and their carers

Freezing of gait (FOG) is difficult to measure due to its unpredictable occurrence. This study investigated: (1) whether the new freezing of gait questionnaire (NFOG-Q) is a reliable measure of freezing by comparing patients’ ratings with those of carers’ and (2) whether adding a video improved its reliability. Non-demented people with Parkinson's disease (PD) (N = 102) and their carers of similar age and cognitive status were recruited from movement disorders clinics in three countries. The NFOG-Q was administered to carers and patients independently before and after watching a video showing several examples of FOG. Patients had very high agreement between their pre- and post-video detection of FOG (Kappa = 0.91). However, this was less than in carers (Kappa = 0.79). The video had a significant influence (p = 0.01) on the rating of FOG severity (duration) but not on the estimation of its functional impact. Post-video freezing severity scores in the 69 freezers showed high agreement with carers’ scores (ICC = 0.78 [0.65;0.87]). We conclude that the NFOG-Q is a reliable tool to detect and evaluate the impact and severity of FOG. Adding a video does not add to the sensitivity and specificity of FOG detection but influences the estimation of FOG severity.