A Biomechanical Double Sac (Pericardium-Pebax) for Specially Shaped Artificial Ventricles: A Computerized Study to Evaluate Its Mechanical and Volumetric Properties

Abstract: For original ovoid shaped artificial ventricles. a biomechanical double sac consisting of a biological sac (porcine pericardium) as the blood contact interface and a synthetic sac (Pebax 3533) as the mechanical support to assume systolic-diastolic dynamic constraints was conceived. The volumetric and mechanical properties were assessed with a three-dimensional modeling of Pebax sacs and computerized simulations of their systolic distortions for both right and left ventricular configurations. The stresses and strains of these sacs were represented as quantitative mappings for a maximum end-systolic state and were below the respective threshold values above which the Pebax material is jeopardized for permanent structure impairment. After fatigue tests applied on Pebax strips under the alleged working conditions of Pebax sacs, the material structure was unchanged and maintained its intrinsic mechanical properties. The theoretical maximum stroke volumes were 74.4 cm³ and 62.4 cm for the left and right ventricular configurations, respectively. With these mechanical and volumetric features, the biomechanical double sac concept was considered valid and could be provided for a consequent specific total artificial heart.     

Impact of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) on the speed of triage decision making for emergency department patients presenting with chest pain

Objective: Emergency department (ED) triage for acute cardiac ischemia in the primary teaching hospital in Geneva, Switzerland, is very accurate, but at the cost of very long ED stays. Thus, the authors sought: 1) to determine the impact of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), incorporated into a computerized electrocardiograph, on length of stay and speed of triage decision making for ED patients presenting with symptoms suggesting acute cardiac ischemia, and 2) to study the ACI-TIPI’s impact on physicians of different training levels. Design: A seven-month prospective clinical trial with alternating-month experimental and control periods. Setting: An urban major teaching hospital in Geneva, Switzerland. Participants: Patients over the age of 18 years presenting to the ED with chest pain or other symptoms suggesting acute cardiac ischemia (acute myocardial infarction or unstable angina pectoris). Emergency department physicians, classified as novice (those in their first ED rotations) and experienced (those in their second or later ED rotations). Patients staying overnight in the ED (n=111) were excluded from the analysis. Intervention: During the experimental months, the computerized electrocardiograph printed the ACI-TIPI probability of acute cardiac ischemia at the top of each subject’s electrocardiogram. During control months, the probability was not provided. Measurements and main results: Among the 418 study subjects, for patients with acute ischemia seen by novice clinicians, the use of the ACI-TIPI decreased ED time from presentation to triage decision and ED release by 0.7 hour (19%) (p=0.007). Subgroup analyses for patients with acute myocardial infarction, patients with unstable angina pectoris, and patients given thrombolytic therapy also showed analogous decreases in ED time consistent with this finding. Other key determinants of ED length of stay included: age, whether the coronary care unit was full, whether patients received thrombolytic therapy, and whether admission was during the night shift. The experimental and control groups did not differ in triage disposition appropriateness or mortality. Conclusions: For ED patients with acute cardiac ischemia evaluated by novice clinicians, the ACI-TIPI substantially speeded ED decision making and triage. The suggestion of an impact on different cardiac ischemia subgroups and mortality deserves further larger clinical trials.     

Immunodetection of Tau microtubule-associated protein in human sperm and testis

Dear Editor,
The cytosolic protein Tau is naturally present in human neurons, where it has a pivotal role in controlling microtubule stability. Hyperphosphorylation of Tau （observed during neurodegenerative diseases, such as Alzheimer＇s disease） impairs the protein＇s ability to bind microtubules. This results in microtubule disassembly and the formation of Tau aggregates, Tau protein is also widely expressed in peripheral tissues. In the male reproductive system, screening for Tau has focused solely on the rodent and bovine testis. In the present study, we used immunofluorescence and immunoenzymatic techniques （with a Tau-specific antibody） to investigate the presence of Tau protein in human ejaculated sperm and testicular tissue.     

Effects of a new slow release formulation of caffeine on EEG,psychomotor and cognitive functions in sleep-deprived subjects

Caffeine is a widely-consumed psychoactive substance whose stimulant effects on mood, attention and performance are largely recognised. The central nervous system pharmacodynamic profile of a single oral dose of a new slow release (SR) caffeine formulation (600 mg) was assessed in a randomised, double-blind, crossover, placebo-controlled study. Twelve young, health, male, sleep-deprived (for 36 h) subjects were studied using EEG and various measures of psychomotor and cognitive functions, including critical flicker fusion (CFF), choice reaction task (CRT), tracking, continuous performance task (CPT), Stroop test, body sway and subjective evaluation (Stanford Sleepiness Scale). Caffeine significantly ( < 0/05) antagonised the detrimental effects of sleep-deprivation on EEG (i.e. produced a significant decrease in delta and theta relative power and a significant increase in alpha and beta (12-40 Hz) relative power) and psychomotor performance (significant increase in speed of reaction on the CRT and Stroop tests, significant decrease in body sway, significant increase in accuracy of the CPT and significant reduction in subjective sedation) compared to placebo. The effect peaked 4 h after dosing and was maintained until the end of sleep deprivation (i.e. 24 h after dosing). In conclusion, the present results demonstrate that a single dose of caffeine SR possesses alerting effects which are able to reverse the deleterious effect of 36 h sleep deprivation for at least 24 h. Copyright 2000 John Wiley & Sons, Ltd.     

EEG,MAO-A inhibition,pharmacokinetics and safety of befloxatone in the elderly

Befloxatone is a new reversible and selective MAO-A inhibitor. The present study aimed to assess the pharmacodynamics (EEG profile and MAO-A inhibition using plasma levels of DHPG), pharmacokinetics and safety after a single dose of 10 mg of befloxatone compared to amitriptyline 50 mg in a randomized, double-blind, three-way crossover, placebo-controlled trial involving 12 elderly subjects. Befloxatone did not show any sedative profile on EEG as no significant changes occurred in slow delta and theta waves or in alpha waves. In contrast, befloxatone produced a non-significant decrease in delta relative power and a significant increase in the (12–40 Hz) beta waves compared to placebo and/or amitriptyline depending on the EEG lead. MAO-A inhibition by befloxatone was evidenced by a significant reduction in DHPG plasma levels (peak activity of −85 per cent and AUC_{0–24 h} of −46 per cent compared to placebo). The pharmacokinetics parameters obtained after a single 10-mg oral dose of befloxatone were: t_max, 2 h; C_max, 33·7 ng/ml; t_1/2β, 14·5 h; AUC_0–∞, 255 ng/ml for befloxatone and t_max, 2 h; C_max, 29·4 ng/ml; t_1/2β, 16 h; AUC_0–∞, 596 ng/ml for its main metabolite, O-demethyl befloxatone. These parameters are in the same range as those obtained in healthy young subjects. In conclusion, the present study demonstrated that a single oral dose of 10 mg of befloxatone is safe in the elderly, possesses potent MAO-A inhibition activity and the EEG profile of a non-sedative antidepressant and did not justify dose adjustment compared to young subjects. © 1997 John Wiley & Sons, Ltd.     

Mash1 promotes neuronal differentiation in the retina

Background: Mash1, a mammalian homologue of Drosophila achaete-scute proneural gene complex, plays an essential role in differentiation of subsets of peripheral neurones. Whereas Mash1 is expressed during retinal development, no apparent abnormalities were found during embryogenesis as well as at birth in Mash1-null retina, suggesting that early differentiating cells such as ganglion, amacrine and cone cells develop normally. Because Mash1-null mice die soon after birth, their postnatal development cannot be examined in vivo. Thus, it remains to be determined whether or not Mash1 functions in postnatal development of retina. Results: Here, Mash1 roles in postnatal development of retina was examined by using retinal explant that develops like in vivo retina. Without Mash1, differentiation of late appearing cells such as rod, horizontal, and bipolar cells was delayed and the final number of bipolar cells was significantly reduced. In contrast, vimentin-positive cells (probably Müller glial cells) were increased in Mash1-null retina. Conclusions: These results provide evidence that Mash1 promotes neuronal differentiation during retinal development and is essential for proper ratios of retinal cell types.     

EEG profile of litoxetine after single and repeated administration in healthy volunteers.

1. Litoxetine is a selective serotonin reuptake inhibitor with antidepressant activity in animal models and in depressed patients. 2. This double-blind, cross-over, placebo-controlled study was carried out in 12 healthy young male volunteers. The aim was to assess the EEG profile of litoxetine in parallel with its pharmacokinetics after a single dose or multiple administrations for 4 days (6 doses) of two dosages (10 mg and 25 mg). Spectral analysis of four EEG leads (F4-T4, F3-T3, T4-02 and T3-01) was done up to 12 h post-dose. 3. In single or multiple doses, litoxetine induced EEG changes characterised by a dose-related increase in fast beta energies, mainly beta 2, without any changes in slow waves (delta and theta). A slight reduction in alpha activity occurred only after repeated doses. 4. EEG changes occurred after a single oral administration and lasted at least 12 h with litoxetine blood concentrations ranging from 4 to 10 ng ml-1. With repeated administrations, the pharmacodynamic steady-state was achieved as the increase in beta 2 energies was the same before and 12 h post-dose. These effects occurred with litoxetine blood concentrations ranging from 3 to 7 ng ml-1 with the 10 mg dosage and from 8 to 18 ng ml-1 with the 25 mg dosage. The EEG profile did not change after 4 days of repeated administration, indicating that tolerance did not develop. 5. Cmax and AUC showed proportionality between the administered dosages of 10 and 25 mg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of the new beta-adrenoceptor blocking agent betaxolol (SL 75212) in man after repeated oral administration

(+/-)-1-(Isopropylamino)-3-[p-(2-cyclopropyl-methoxyethyl)-phenoxy]-2-propanol HCl (betaxolol, SL 75212) was given to groups of healthy volunteers, 10 mg daily for 7 days followed by 20 mg daily 7 days in one group, and increasing daily doses up to 60 mg/day for a total of 15 days in the other group. The pharmacokinetics were studied during dosing and in the washout period. The pharmacokinetic characteristics were unchanged after repeated doses, T/2 16-22 h, Vd 7.7-8.8 l/kg; clearance 0.28-0.33 l/h/kg.     

Slow-release caffeine: a new response to the effects of a limited sleep deprivation

STUDY OBJECTIVES: The aim of this study is to assess the interest of the intake of a new galenic form of caffeine called "slow-release" caffeine (SR caffeine) during a decrease of vigilance due to a limited sleep deprivation. DESIGN: The controlled method used compared three doses of SR caffeine (150, 300 and 600 mg) with a placebo. Tests were performed 2, 9 and 13 hours after each treatment. Wakefulness level was assessed subjectively through questionnaires and analog visual scales, and objectively with the Multiple Sleep Latency Test. Performance level was also assessed regularly with an attention test, a grammatical reasoning test, a spatial recognition test, a mathematical processing test, a visual tracking test, a memory search test, and a dual task. The motor activity was evaluated by wrist actimeter and safety of treatment was observed by regular clinical examination. SETTING: NA. PARTICIPANTS: Twenty-four young and healthy volunteers (12 men and 12 women) participated in a 32-hour sleep deprivation. INTERVENTIONS: NA. RESULTS: The results show a significant effect of slow-release caffeine vs. placebo, and on vigilance and performance when subjects became tired. The effects of SR caffeine lasted 13 hours after treatment. SR caffeine 300 and 600 mg are efficacious doses but the optimal dose (maximum effect without any side effects) for both men and women is after all 300 mg. Globally, there is no difference between placebo and caffeine during the recovery night period. CONCLUSIONS: SR caffeine (300 mg) seems to be an efficient and safety substance to maintain a good level of vigilance and performance during limited sleep deprivation.