Correlation between cognitive deficits and Abeta deposits in transgenic APP+PS1 mice.

Doubly transgenic mAPP+mPS1 mice (15-16 months) had impaired cognitive function in a spatial learning and memory task that combined features of a water maze and a radial arm maze. Nontransgenic mice learned a new platform location each day during 4 consecutive acquisition trials, and exhibited memory for this location in a retention trial administered 30 min later. In contrast, transgenic mice were, on average, unable to improve their performance in finding the hidden platform over trials. The cognitive performance of individual mice within the transgenic group were inversely related to the amount of Abeta deposited in the frontal cortex and hippocampus. These findings imply that mAPP+mPS1 transgenic mice develop deficits in cognitive ability as Abeta deposits increase. These data argue that radial arm water maze testing of doubly transgenic mice may be a useful behavioral endpoint in evaluating the functional consequences of potential AD therapies, especially those designed to reduce Abeta load.

Progressive, age-related behavioral impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1 transgenes.

This study provides a comprehensive behavioral characterization during aging of transgenic mice bearing both presenilin-1 (PS1) and amyloid precursor protein (APP(670,671)) mutations. Doubly transgenic mice and non-transgenic controls were evaluated at ages wherein beta-amyloid (Abeta) neuropathology in APP+PS1 mice is low (5-7 months) or very extensive (15-17 months). Progressive cognitive impairment was observed in transgenic mice for both water maze acquisition and radial arm water maze working memory. However, transgenicity did not affect Y-maze alternations, circular platform performance, standard water maze retention, or visible platform recognition at either age, nor did transgenicity affect anxiety levels in elevated plus-maze testing. In sensorimotor tasks, transgenic mice showed a progressive increase in open field activity, a progressive impairment in string agility, and an early-onset impairment in balance beam. None of these sensorimotor changes appeared to be contributory to any cognitive impairments observed, however. Non-transgenic mice showed no progressive behavioral change in any measure evaluated. Given the age-related cognitive impairments presently observed in APP+PS1 transgenic mice and their progressive Abeta deposition/neuroinflammation, Abeta neuropathology could be involved in these progressive cognitive impairments. As such, the APP+PS1 transgenic mouse offers unique opportunities to develop therapeutics to treat or prevent Alzheimer's Disease through modulation of Abeta deposition/neuroinflammation.

Preliminary evaluation of a prototype tube-valve-mask ventilator for emergency artificial ventilation.

STUDY OBJECTIVE: The objective was to design a prototype tube-valve-mask ventilator that would permit relatively inexperienced operators to provide adequate emergency artificial ventilation, namely, adequate ventilatory volumes and a high oxygen and low carbon dioxide delivery. DESIGN: The tube-valve-mask ventilator is powered by the exhaled air of the operator and uses a tube to act as an oxygen reservoir (1,300 mL) that is filled between breaths. Mouth-to-mouth breathing was the standard against which the tube-valve-mask ventilator and the other accepted methods of mouth-to-mask and bag-valve-mask were assessed. SETTING: Comparison studies were conducted during simulated two-person CPR using a training mannikin equipped to measure ventilation volume and delivered oxygen and carbon dioxide concentrations. TYPE OF PARTICIPANTS: Seventeen volunteer first-year nursing students were used as operators. INTERVENTIONS: The order in which the pairs of operators performed each of the techniques was randomized. MEASUREMENTS AND MAIN RESULTS: The ventilation volume and the percentage of oxygen and carbon dioxide delivered by each technique were as follows (mean +/- SD): Mouth-to mouth (760 +/- 290 mL, 17 +/- 1% O2, 3.4 +/- 0.4% CO2), mouth-to-mask (910 +/- 350 mL, 41 +/- 8% O2, 2.5 +/- 0.4% CO2), bag-valve-(soft) mask (550 +/- 230 mL, 94 +/- 3% O2, 0.03 +/- 0.02% CO2), bag-valve-(rigid) mask (560 +/- 300 mL, 96 +/- 3% O2, 0.03 +/- 0.02% CO2), and tube-valve-mask (860 +/- 290 mL, 91 +/- 7% O2, 0.2 +/- 0.2% CO2). CONCLUSION: In the hands of relatively inexperienced operators, mouth-to-mouth, mouth-to-mask, and tube-valve-mask techniques provide adequate ventilation volumes to a mannikin. This was not the case with the bag-valve-mask systems (800 mL; P = .05 by t test). Of the systems that provide adequate ventilation volume, the tube-valve-mask appears, superior in that higher oxygen and lower carbon dioxide concentrations can also be obtained (P = .05 by paired t test).

Understanding and selecting monitoring equipment in anaesthesia and intensive care.

Techniques for sensing, acquiring, processing and displaying physiological variables used to assist the process of monitoring in anaesthesia and intensive care have been reviewed. The role of instrumental monitoring in clinical practice and the comparative effectiveness of Man versus Machine has been outlined. Future developments in monitoring in clinical practice have been identified. It is important that physicians stay abreast of developments in the technology of measurement and monitoring instrumentation so that they not only assist in the development of standards but also have a complete understanding of the precision and real usefulness of any given item of equipment. To this end, guidelines have been tabulated which may permit those who have the responsibility for acquiring updating or using monitoring equipment, to more completely examine the features of any apparatus which is being considered for purchase.

Epidural morphine prophylaxis of postoperative pain: report of a double-blind multicentre study.

In a double-blind placebo-controlled trial, 154 subjects, having intraperitoneal surgery or Caesarean section, and 53 patients undergoing lower limb orthopaedic surgery, received epidural morphine, 5 mg in 10 ml 0.9 per cent NaCl, or placebo, 10 ml 0.9 per cent NaCl, intraoperatively to determine duration of action and efficacy in preventing postoperative pain. Epidural morphine gave significantly longer postoperative analgesia (greater than 11 h) than placebo (3-6 h) in both groups (p less than 0.05) and patients who received morphine required less postoperative analgesic. Obstetric subjects experienced longer pain relief (18.3 +/- 1.3 h) than patients undergoing non-obstetric intraperitoneal surgery (9.2 +/- 1.2 h) (p less than 0.001). Generally mild pruritus affected more than 40 per cent of those receiving morphine, but over 90 per cent of obstetric patients receiving morphine. Respiratory depression occurred in 2-7 per cent of subjects who received morphine; unpredictable in onset, it responded rapidly to naloxone. Epidural bupivacaine, if employed for the surgical procedure, appeared to prolong epidural morphine analgesia. We consider epidural morphine useful in preventing postoperative pain, but its use demands close observation of respiratory rate in a high density nursing area.

Ankylosis of the temporo-mandibular joint after temporal craniotomy: a cause of difficult intubation.

It is not generally appreciated that surgery in the region of the temporal fossa commonly produces, within a few weeks, a contracture of the temporalis muscle with "pseudo" ankylosis of the jaw. This usually, but not always, resolves within six months. The aetiological possibilities include, singly or in combination: Postincisional scar formation within the muscle. A Volkman's contracture due to devascularization of the muscle. Organization of haematoma. It is recommended that active and passive jaw exercises be started early after surgery in the temporal fossa and that such postcraniectomy patients be carefully assessed for jaw ankylosis prior to undertaking anaesthesia.

Some pharmacological properties of althesin (CT1341) in man.

Althesin in dose ranges of 40, 60 and 80 mul/Kg was administered to six healthy unpremedicated volunteers according to a balanced incomplete block design. Both subjective and objective changes resulting from the administration of the agent were studied and analyzed. In the dose ranges used, Althesin was found to have no deleterious effects on heart rate, respiratory rate or blood pressure and apnoea only occurred in one patient who had an end-expiratory CO2 level lower than normal, due to preanaesthetic hyperventilation. The onset of sleep is prolonged with Althesin at the injection rate of 1 ml/10 secs. The onset of anaesthesia is not influenced by the total dose, but the sleep time is directly proportional to the dose injected. Auditory evoked responses tended to lie on a curve which might indicate that with increasing dose the time to reappearance of these responses is not correspondingly prolonged. However, this last observation must be confirmed by studies on a larger scale.