Reviews: Effects of transdermal rivastigmine on ADAS-cog items in mild-to-moderate Alzheimer's disease

Alzheimer's disease (AD) patients treated with rivastigmine transdermal patch have shown statistically significant differences versus placebo on the AD Assessment scale-cognitive subscale (ADAS-cog). In this retrospective analysis of a double-blind, placebo- and active-controlled, 24-week clinical trial, the specific effects of rivastigmine patch on individual ADAS-cog items and cognitive domains (memory, language, and praxis) were explored. The mean baseline to week 24 changes were calculated for each ADAS-cog item and domain in this exploratory, hypothesis-generating analysis. Patients on 9.5 mg/24 h rivastigmine patch, 17.4 mg/24 h rivastigmine patch, and 3 to 12 mg/d rivastigmine capsules showed improvements over placebo on the memory and praxis ADAS-cog subscales. The rivastigmine patch groups also showed improvements on the language subscale. Significant differences versus placebo were seen on several individual item scores in the rivastigmine-treated groups. Rivastigmine patch was associated with improvements on the memory, praxis, and language domains of cognition in patients with mild-to-moderate AD.     

Systematic evaluation of the highest current threshold for regional anaesthesia in a porcine model

Background: The purpose of this study was to determine systematically the highest minimal stimulation current threshold for regional anaesthesia in pigs. Methods: In an established pig model for regional anaesthesia, needle placements applying electric nerve stimulation were performed. The primary outcome was the frequency of close needle to nerve placements as assessed by resin injectates and subsequent anatomical evaluation. Following a statistical model (continual reassessment method), the applied output currents were selected to limit the necessary number of punctures, while providing guidance towards the highest output current range. Results: Altogether 186 punctures were performed in 11 pigs. Within the range of 0.3–1.4 mA, no distant needle to nerve placement was found. In the range of 1.5–4.1 mA, 43 distant needle to nerve placements occurred. The range of 1.2–1.4 mA was the highest interval that resulted in a close needle to nerve placement rate of ≥95%. Conclusions: In the range of 0.3–1.4 mA, all resin deposition was found to be adjacent to nerve epineurium. The application of minimal current intensities up to 1.4 mA does not obviously lead to a reduction of epineural injectate contacts in pigs. These findings suggest that stimulation current thresholds up to 1.4 mA result in equivalent needle tip localisation in pigs.     

Projekt „Spotlight Erste Hilfe“

Background

To obtain a driving license in Austria it is obligatory to attend first aid training. However, according to the traffic patrol and emergency medical services only a minority of drivers is willing to provide first aid or the quality of first aid offered is poor.

Method

Theoretical and practical first aid knowledge and basic life support skills in addition to demographic data were evaluated in standardized face-to-face interviews and a simulated cardiac arrest scenario.

Results

Overall 597 drivers (43% male) with a median age of 35 years were surveyed. Of the participants 42.2% had attended first aid training more than 10 years ago and only 16.4% within the last year. Of the participants 32% had graduated from high school as the highest educational achievement. The Austrian emergency telephone codes were remembered correctly by 88%. All participants were willing to give information on why they would omit first aid and for 68% the primary cause was fear of providing first aid in an incorrect manner. A total of 182 persons (30.5%) agreed to demonstrate their resuscitation skills in a simulated cardiac arrest situation. The check of consciousness was performed correctly by 83%, the emergency call by 74%, clearing the airway by 30% and assessment of breathing by 46% of the participants. Chest compression and ventilation were delivered by 87% but only 19% carried this out in a correct manner. The longer the last first aid training dated back, the worse were the results (Spearman correlation coefficient r=?0.310; p=0.01).

Conclusion

In a random sample of Austrian car drivers the latest first aid training dated back more than 10 years in 42.2%. Practical skills in a simulated cardiac arrest scenario were sufficient only in a very low percentage of the drivers.     

Conscious Sedation and Anesthesia in the Cardiac Electrophysiology Laboratory

Conscious Sedation and Anesthesia. Adequate anesthesia is important for performing EP procedures such as catheter ablation and implantation of cardiac devices. A wide range of anesthesia options are available, and all can be safely administered in EP laboratory with proper monitoring, drug selection, airway management equipment, and trained personnel. In addition to knowing the patient's clinical status, a thorough understanding of the clinical pharmacology of each anesthetic agent is essential in order to select appropriate drug among a variety of available anesthetics, to monitor for adverse effects, and to ensure adequate sedation and anesthesia for a comfortable, safe, and successful procedure. After a general strategy of anesthesia is planned, an individual anesthetic agent or combination of agents can be selected based on their pharmacological properties while keeping in mind the desired sedation/anesthesia requirements. Since anesthetics are often used in combination, the synergistic interaction of several anesthetic agents (infiltrative, parenteral, and/or inhaled) needs to be considered. Further attention also needs to be paid to the interaction between anesthetics and other existing medications. Finally, all care providers should work collaboratively and communicate frequently to provide a safe and effective anesthesia. (J Cardiovasc Electrophysiol, Vol. 24, pp. 237‐245, February 2013)     

Efficacy of etanercept and complete decongestive physical therapy in bilateral lower-limb lymphoedema associated with rheumatoid arthritis: A case report

A 54-y-old patient with rheumatoid arthritis (RA) and bilateral lower-limb lymphoedema is presented. Complete decongestive physical therapy (CDP) is the cornerstone of the management programme in all patients suffering from lymphoedema associated with RA, but it is not clear which therapy is the most effective in decreasing the oedema. We report on a patient with bilateral lower-limb lymphoedema associated with RA who, after receiving etanercept and CDP, showed moderate improvement. There is little information on the benefit of etanercept therapy for the extra-articular manifestations of RA. Further research is necessary to confirm the beneficial effect of etanercept and CDP.     

Milnacipran attenuates hyperalgesia and potentiates antihyperalgesic effect of tramadol in rats with mononeuropathic pain

Milnacipran is a non-tricyclic antidepressant drug which selectively inhibits serotonin and noradrenaline re-uptake and is recommended in the treatment of various chronic pain syndromes. Many studies have shown that compounds known to block monoamine uptake potentiate the antinociceptive effects of opioids. This study investigates the effect of milnacipran alone or in combination with an opiodergic drug, i.e. tramadol, on hyperalgesia in a rat model of neuropathic pain. The contribution of serotonergic, noradrenergic and opioidergic systems in the potential antihyperalgesic effect of milnacipran has also been examined. Chronic constriction injury was induced in rats by loose ligation of the sciatic nerve and neuropathic pain was evaluated 14 days after surgery. Intraperitoneal acute injection of milnacipran 60 mg/kg produced an antihyperalgesic effect which was prevented by pretreating systemically with alpha-methyl-p-tyrosine, an inhibitor of noradrenaline synthesis; parachlorophenylalanine, an inhibitor of serotonin synthesis; and naloxone, an antagonist of opioidergic receptors. Co-administration of milnacipran 40 mg/kg with tramadol (20 and 40 mg/kg) potentiated the antihyperalgesic effect of tramadol. Milnacipran has an antihyperalgesic effect mediated by serotonergic, noradrenergic and opioidergic systems and the combined use of tramadol with milnacipran potentiates the effect of tramadol in the management of neuropathic pain.     

The impact of radiological anatomy in clearance of lower caliceal stones after shock wave lithotripsy

The goal of this study was to determine the factors affecting stone clearance after extracorporeal shock wave lithotripsy (ESWL) for lower caliceal stones. Lower pole stone clearance was investigated in 128 (80 males, 48 females) patients treated with ESWL during 1998–2003 in our clinic. Renal anatomy was determined on standard intravenous urogram. The lower infundibulopelvic angle (LIPA) was measured as the angle between the vertical pelvis axis and the vertical axis of lower infundibulum (Sampaio’s method). The mean age of the patients was 42.8 ± 12.4 (19–77) years. The mean stone diameter and burden were found to be 1.28 ± 0.58 (0.5–3.5) cm and 1.2 ± 1 (0–7) cm² respectively. The stone-free rate was 62.5% and ESWL was unsuccessful in 16 (12.5%) patients. Thirty-two (25%) patients had residual fragments ≤4 mm retained in lower calices after lithotripsy. The stone clearance was found to be unrelated to stone burden and diameter (P = 0.17 and P = 0.14, respectively). However, there was a significant difference between mean lower pole infundibulum length (P = 0.001), infundibulum width (P = 0.001) and LIPA (P = 0.0001) between stone-free patients and patients with residual fragments. Multivariate logistic regression analysis accepting stone-free as the favourable result also confirmed that LIPA, lower pole infundibulum length and width were factors that significantly affected the outcome. Lower pole anatomy has a significant influence on clearance of fragments after ESWL.     

Interaction of kinesin motors, microtubules, and MAPs

Kinesins are a family of microtubule-dependent motor proteins that carry cargoes such as vesicles, organelles, or protein complexes along microtubules. Here we summarize structural studies of the “conventional” motor protein kinesin-1 and its interactions with microtubules, as determined by X-ray crystallography and cryo-electron microscopy. In particular, we consider the docking between the kinesin motor domain and tubulin subunits and summarize the evidence that kinesin binds mainly to β tubulin with the switch-2 helix close to the intradimer interface between α and β tubulin.