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Onset Time (onset + time)

Distribution by Scientific Domains

Medical Sciences	73%
Life Sciences	13%
Mathematics and Statistics	8%
Earth and Environmental Science	4%

Distribution within Medical Sciences

Anesthesia & Pain Management	54%
Neurology	8%
10 Other Subdomains	38%

Selected Abstracts

Time course of rocuronium-induced neuromuscular block after pre-treatment with magnesium sulphate: a randomised study

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2010
C. CZARNETZKI
Background: A previously published study suggested that pre-treatment with magnesium sulphate (MgSO4) had no impact on the speed of onset of rocuronium-induced neuromuscular block. We set out to verify this assumption. Methods: Eighty patients (18,60 years) were randomly allocated to MgSO4 60 mg/kg or placebo (saline). Study drugs were given intravenously for 15 min before induction of anaesthesia with propofol, sufentanil and rocuronium 0.6 mg/kg. Anaesthesia was maintained with a target-controlled propofol infusion. Neuromuscular transmission was measured using train-of-four (TOF)-Watch SX® acceleromyography. Results: Onset was analysed in 37 MgSO4 and 38 saline patients, and recovery in 35 MgSO4 and 37 saline patients. Onset time (to 95% depression of T1) was on average 77 [SD=18] s with MgSO4 and 120 [48] s with saline (P<0.001). The total recovery time (DurTOF0.9) was on average 73.2 [22] min with MgSO4 and 57.8 [14.2] min with saline (P<0.003). The clinical duration (Dur25%) was on average 44.7 [14] min with MgSO4 and 33.2 [8.1] min with saline (P<0.0002). The recovery index (Dur25,75%) was on average 14.0 [6] min with MgSO4 and 11.2 [5.2] min with saline (P<0.02). The recovery time (Dur25%TOF0.9) was on average 28.5 [11.7] min with MgSO4 and 24.7 [8.4] min with saline (P=0.28). Conclusion: Magnesium sulphate given 15 min before propofol anaesthesia reduces the onset time of rocuronium by about 35% and prolongs the total recovery time by about 25%. Trial Registration: Clinicaltrials.gov identifier: NCT00405977. [source]

Mandibular kinematics associated with simulated low-velocity rear-end impacts

JOURNAL OF ORAL REHABILITATION, Issue 8 2006
I. A. HERNÁNDEZ
summary, Rear-end-impact motor vehicle accidents may result in cervical and temporomandibular-related pain complaints. Head kimematics in simulated low-impact rear-end impacts have been investigated but mandibular kinematics have not been described. Thirty healthy adult subjects underwent three impacts (4·5 m s,2 expected, 10·0 m s,2 unexpected, and 10·0 m s,2 expected). Onset time and peak magnitude of angular head acceleration, angular mandibular acceleration and angular mandibular displacement were measured. Significant mandibular opening acceleration was not identified with rearward head rotation. The peak magnitude of mandibular closing angular acceleration approximately doubled with increased impact magnitude. No differences in peak angular mandibular acceleration regarding expectation were identified. Gender differences were detected in the fast unexpected impact. The peak time for the angular mandibular acceleration (mandibular closure) was approximately 84,120 ms later than peak rearward angular head acceleration for all impacts. Onset and peak times for angular mandibular acceleration (mandibular closure) were similar to the onset and peak times for forward head acceleration. There was also a positive correlation between the magnitude of the forward angular acceleration of the head and angular acceleration of the mandible for the slow (0·65, P = 0·015) and fast expected (0·844, P = 0·001) impacts. The average angular mandibular angular displacement (mandibular closure) was approximately 6°. The hyperextension hypothesis regarding mechanism of temporomandibular joint injury in low-impact rear-end collisions cannot be supported. [source]

Effects of SZ1677, a new non-depolarizing steroidal neuromuscular blocking drug, and rocuronium on two laryngeal muscles and the anterior tibial muscle in guinea pigs

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2006
A. Michalek-Sauberer
Background:, SZ1677 is a new neuromuscular blocking drug structurally related to rocuronium. We compared the effect of an ED90 of SZ1677 (25 ,g/kg) with that of rocuronium (100 ,g/kg) in guinea pig laryngeal and peripheral muscles. Methods:, Electromyography was used to quantify neuromusc-ular blockade at the posterior cricoarytenoid muscle, the thyroarytenoid muscle and the anterior tibial muscle after SZ1677 (n = 10) and rocuronium (n = 9). Results:, Maximum neuromuscular blockade was similar after SZ1677 and rocuronium (83 ± 11% vs. 89 ± 11%; thyroarytenoid muscle: 91 ± 8% vs. 97 ± 3%; anterior tibial muscle: 91 ± 15% vs. 96 ± 3%, respectively). Onset time of neuromuscular blockade at the laryngeal muscles was similar for the two neuromuscular blocking drugs; it was shorter at the thyroarytenoid muscle (67 ± 32 s vs. 42 ± 40 s) than at the posterior cricoarytenoid muscle (101 ± 26 s vs. 102 ± 108 s). Onset time at the anterior tibial muscle was longer after SZ1677 (114 ± 34 s) than after rocuronium (68 ± 46 s); P < 0.05. Neuromuscular recovery was faster after SZ1677 (interval 25%,75%: posterior cricoarytenoid muscle: 222 ± 66 s; thyroarytenoid muscle: 192 ± 92 s; tibial muscle 149 ± 55 s) than after rocuronium (450 ± 148 and 464 ± 183 s, 292 ± 86 s, respectively); P < 0.05. Conclusions:, In guinea pigs, SZ1677 offers a rapid onset of neuromuscular blockade at a laryngeal adductor muscle with a shorter duration than rocuronium. Regardless of the drug used, the course of neuromuscular blockade differs not only between peripheral muscles and the larynx but also between antagonistic laryngeal muscles. The differences seem to be species specific. [source]

Ultrasound vs nerve stimulation multiple injection technique for posterior popliteal sciatic nerve block

ANAESTHESIA, Issue 6 2009
G. Danelli
Summary In this prospective, randomised, observer-blinded study we evaluated whether ultrasound guidance can shorten the onset time of popliteal sciatic nerve block as compared to nerve stimulation with a multiple injection technique. Forty-four ASA I,III patients undergoing posterior popliteal sciatic nerve block with 20 ml of 0.75% ropivacaine were randomly allocated to nerve stimulation or ultrasound guided nerve block. A blinded observer recorded onset of sensory and motor blocks, success rates, the need for fentanyl intra-operatively, the requirement for general anaesthesia, procedure-related pain, patient satisfaction and side-effects. Onset times for sensory and motor blocks were comparable. The success rate was 100% for ultrasound guided vs 82% for nerve stimulation (p = 0.116). Ultrasound guidance reduced needle redirections (p = 0.01), were associated with less procedural pain (p = 0.002) and required less time to perform (p = 0.002). Ultrasound guidance reduced the time needed for block performance and procedural pain. [source]

Effects of labedipinedilol-A, third-generation dihydropyridine-type calcium blocker, on ouabain-induced arrhythmia

DRUG DEVELOPMENT RESEARCH, Issue 1 2008
Jhy-Chong Liang
Abstract Labedipinedilol-A, a novel dihydropyridine-type calcium antagonist with ,/,-adrenoceptor blocking properties, has been reported to produce a cardioprotective effect against ischemia reperfusion injury in rats. We investigated the protective effects of labedipinedilol-A on ouabain-induced tonotropy and arrhythmias in isolated whole atria, and using patch-clamp techniques to study the underlying mechanism of its antiarrhythmic activity on isolated cardiac myocytes. Labedipinedilol-A (10,µM) suppressed the tonotropic effect of ouabain significantly and prolonged the onset time of extra-systole (arrhythmia) induced by ouabain in isolate atria. In the voltage-clamp study, labedipinedilol-A (1,100,µM) reduced the peak amplitude of sodium inward current (INa) and L-type calcium current (ICa-L), and shifted the current-voltage (I-V) curve upward in a concentration-dependent manner. In contrast, the addition of labedipinedilol-A increased transient outward potassium current (Ito) and inward rectifier potassium current (IK1) significantly. Labedipinedilol-A (10,µM) also effectively depressed the isoproterenol-induced increase in the Ca2+ current. These results show that labedipinedilol-A blocks ICa-L and INa, and increases Ito and IK1. These findings indicate that labedipinedilol-A produces direct cardiac action, probably due to the inhibition of cardiac Na+ and Ca2+ channels. Our results suggest that labedipinedilol-A may reduce the membrane conduction through inhibition of ionic channels which decrease ouabain-induced arrhythmia. Drug Dev Res 69:26,33, 2008 © 2008 Wiley-Liss, Inc. [source]

Therapeutic Yield and Outcomes of a Community Teaching Hospital Code Stroke Protocol

ACADEMIC EMERGENCY MEDICINE, Issue 4 2004
Andrew W. Asimos MD
Objectives: To describe the experience of a community teaching hospital emergency department (ED) Code Stroke Protocol (CSP) for identifying acute ischemic stroke (AIS) patients and treating them with tissue plasminogen activator (tPA) and to compare outcome measures with those achieved in the National Institute of Neurological Disorders and Stroke (NINDS) trial. Methods: This study was a retrospective review from a hospital CSP registry. Results: Over a 56-month period, CSP activation occurred 255 times, with 24% (n= 60) of patients treated with intravenous (IV) tPA. The most common reasons for thrombolytic therapy exclusion were mild or rapidly improving symptoms in 37% (n= 64), intracerebral hemorrhage (ICH) in 23% (n= 39), and unconfirmed symptom onset time for 14% (n= 24) of patients. Within 36 hours of IV tPA treatment, 10% (NINDS = 6%) of patients (n= 6) sustained a symptomatic ICH (SICH). Three months after IV tPA treatment, 60% of patients had achieved an excellent neurologic outcome, based on a Barthel Index of ,95 (NINDS = 52%), while mortality measured 12% (NINDS = 17%). Among IV tPA-treated patients, those developing SICH were significantly older and had a significantly higher mean initial glucose value. Treatment protocol violations occurred in 32% of IV tPA-treated patients but were not significantly associated with SICH (Fisher's exact test). Conclusions: Over the study period, the CSP yielded approximately one IV tPA-treated patient for every four screened and, despite prevalent protocol violations, attained three-month functional outcomes equal to those achieved in the NINDS trial. For community teaching hospitals, ED-directed CSPs are a feasible and effective means to screen AIS patients for treatment with thrombolysis. [source]

The sublethal effects of tebufenozide on the precopulatory and copulatory activities of Choristoneura fumiferana and C. rosaceana

ENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 3 2004
Renée Dallaire
Abstract The sublethal effects of tebufenozide, an ecdysone agonist, on the reproductive biology of Choristoneura fumiferana (Clem) and of Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae), treated during the larval stage, were evaluated using two treatment methods: the force-feeding method and the diet method. The percentage of mortality and the developmental time of survivors increased linearly with the concentration of tebufenozide used. This ecdysone analogue proved to be more toxic to C. fumiferana than to C. rosaceana. In C. rosaceana, the weight of males and females decreased proportionally with the dose ingested, but females were affected to a greater extent. This difference might be due to a greater consumption of the treated diet, or to a differential vulnerability to tebufenozide. Tebufenozide did not modify the pre-copulatory activities associated with chemical communication in the females. However, the consumption of tebufenozide delayed ovarian maturation, causing a reduction in the fecundity of females. Treated males had smaller spermatophores and fewer eupyrene sperms in their bursa copulatrix and spermatheca, along with lower mating success. In C. fumiferana, tebufenozide delayed the females' onset time of calling the first night after emergence, but did not affect the mean time spent calling or the production of the main component of the sex pheromone. The males showed significantly greater difficulty in executing oriented flight in a wind tunnel, although their mating success was not affected. We concluded that tebufenozide interferes with various aspects of the reproductive biology of males and females of C. fumiferana and C. rosaceana, including some pre-copulatory behaviors associated with sex pheromone communication. [source]

Effect of recombinant factor VIIa variant (NN1731) on platelet function, clot structure and force onset time in whole blood from healthy volunteers and haemophilia patients

HAEMOPHILIA, Issue 5 2007
D. F. BROPHY
Summary., NN1731 is a novel variant of recombinant factor VIIa (rFVIIa) that binds to activated platelets, but has greater enzymatic activity than rFVIIa in generating FXa and thrombin. The effect of NN1731 on clot structure and platelet function was characterized ex vivo in whole blood from healthy volunteers and haemophilic patients. Blood samples from six healthy volunteers, nine haemophilia A patients with and without inhibitors and one acquired haemophilia A patient, were spiked with increasing concentrations (0.32, 0.64 and 1.28 ,g mL,1) of rFVIIa and NN1731. Platelet contractile force (PCF) or platelet function, clot elastic modulus (CEM) or clot structure, and force onset time (FOT) or the thrombin generation time (TGT) were determined using the Hemodyne Hemostasis Analysis System (HASÔ). Baseline PCF, CEM and FOT values in patients were abnormal compared to healthy volunteers' baseline values. Overall, haemophilia blood samples with or without inhibitors spiked with NN1731 had significantly greater PCF, CEM and shorter FOT values relative to samples spiked with corresponding doses of rFVIIa. The variability in response to treatment between patients was greater with rFVIIa compared to NN1731. At 1.28 ,g mL,1 (90 ,g kg,1), NN1731 normalized PCF, CEM and FOT in nine of 10 patients, while rFVIIa normalized these parameters in four of 10 patients. Increasing in vitro concentrations of NN1731 normalized platelet function, clot structure and thrombin generation consistently in haemophilia blood with or without inhibitors. NN1731 may be a promising haemostatic agent for patients with bleeding disorders. These results should be confirmed in an in vivo study. [source]

Is nerve stimulation needed during an ultrasound-guided lateral sagittal infraclavicular block?

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010
Y. GÜRKAN
Background: The objective of the study was to evaluate the influence of ultrasound (US) guidance alone vs. neurostimulation (NS) and US (NSUS) guidance techniques on block performance time and block success rate for the lateral sagittal infraclavicular block (LSIB). Methods: In a randomized and prospective manner, 110 adult patients scheduled for distal upper limb surgery were allocated to the US or the NSUS groups. In the US group, a local anesthetic (LA) was administered only with US guidance to produce a ,U'-shaped distribution around the axillary artery. In the NSUS group, LA was administered under US guidance only after electrolocation of one of the median, ulnar or radial nerve-type responses. A total of 30 ml of LA (10 ml of levobupivacaine 5 mg/ml and 20 ml of lidocaine 20 mg/ml) was administered in both groups. Sensory block was tested at 10 min intervals for 30 min. Successful block was defined as analgesia or anesthesia of all five nerves distal to the elbow. Results: Block success rate was 94.5% in both groups. Block performance time was significantly shorter in the US than the NSUS group (157 ± 50 vs. 230 ± 104 s) (P=0.000). Block onset time was similar in both groups (12.5 ± 4.8 in the US vs. 12.8 ± 5.4 min in the NSUS groups). There were two arterial punctures in the NSUS group. Conclusions: During LSIB performance US guidance alone produces block success rate identical to both US and NS guidance yet with a shorter block performance time. [source]

Intrathecal sufentanil decreases the median effective dose (ED50) of intrathecal hyperbaric ropivacaine for caesarean delivery

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2010
X. CHEN
Background: The addition of opioid to local anaesthetics has become a well-accepted practice of spinal anaesthesia for caesarean delivery. Successful caesarean delivery anaesthesia has been reported with the use of a low dose of intrathecal hyperbaric ropivacaine coadministered with sufentanil. This prospective, double-blinded study determined the median effective dose (ED50) of intrathecal hyperbaric ropivacaine with and without sufentanil for caesarean delivery, to quantify the sparing effect of sufentanil on the ED50 of intrathecal hyperbaric ropivacaine. Methods: Sixty-four parturients undergoing elective caesarean delivery with combined spinal,epidural anaesthesia were randomized into two groups: Group R (ropivacaine) and Group RS (ropivacaine plus sufentanil 5 ,g). The initial dose of ropivacaine was 13 mg in Group R and 10 mg in Group RS. The effective dose was defined as a T6 level attained within 10 min and no supplemental epidural anaesthetic required during surgery. Effective or ineffective responses determined, respectively, a 0.3 mg decrease or increase of the dose of ropivacaine for the next patient using an up,down sequential allocation. Results: The ED50 of intrathecal ropivacaine was 11.2 mg [confidence interval (CI) 95%: 11.0,11.6] in Group R vs. 8.1 mg (CI 95%: 7.8,8.3) in Group RS. Motor block was markedly more intense in Group R than in Group RS, and the incidence of shivering was lower in Group RS than in Group R. There were no differences in the onset time of sensory block or motor block, in the incidence of hypotension, nausea and vomiting. Conclusion: Intrathecal sufentanil 5 ,g produced a 28% reduction of ED50 of intrathecal hyperbaric ropivacaine for caesarean delivery. [source]

Time course of rocuronium-induced neuromuscular block after pre-treatment with magnesium sulphate: a randomised study

Calling behaviour of adult female Helicoverpa armigera (Hübner) (Lep., Noctuidae) of overwintering generation and effects of mating

JOURNAL OF APPLIED ENTOMOLOGY, Issue 2 2000
M. L. Hou
The calling behaviour of overwintering generation females of Helicoverpa armigera and the effects of mating were studied in the laboratory at 24 ± 1°C and under reversed light-dark cycle (16 h light : 8 h dark). Age had a significant influence on calling patterns. Based on calling age, mean number of calling bouts and total calling length of virgin females increased significantly, and mean onset time of calling advanced significantly from calling day 1 to subsequent calling days. Females of the overwintering generation exhibited more short bouts in calling, and some females that initiated calling on a previous day did not call on subsequent days. Mating had no effect on the overall patterns, but did affect calling behaviour. Mated females did not resume calling after mating during the same scotophase and, on the day following mating, mated females called less frequently and for a shorter duration, but thereafter increased to the same level of virgin females of the same calling age. Furthermore, as the moth aged, the percentage of mated females calling was lower than that of virgin females. [source]

Single vs. double stimulation during a lateral sagittal infraclavicular block

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2009
E. AKY
Background: The objective of this study was to evaluate the influence of single vs. dual control during an ultrasound-guided lateral sagittal infraclavicular block on the efficacy of sensory block and the time of block onset. Methods: In a prospective manner, 60 adult patients scheduled for distal upper limb surgery were randomly allocated to single (Group S) or double stimulation (Group D) groups. A local anesthetic (LA) mixture of 20 ml of levobupivacaine 5 mg/ml and 20 ml of lidocaine 20 mg/ml with 5 ,g/ml epinephrine (total 40 ml) was administered in both groups. In the Group S following a median, an ulnar or a radial nerve response, the entire LA was administered at a single site. In Group D 10 ml of LA was administered following the electrolocation of the musculocutaneous nerve and 30 ml LA was injected following median, ulnar or radial nerves. A successful block was defined as analgesia or anesthesia of all five nerves distal to the elbow. Sensory and motor blocks were tested at 5-min intervals for 30 min. Results: The block was successful in 27 patients in Group S and 28 patients in Group D. The time from starting the block until satisfactory anesthesia was significantly shorter in Group D than in Group S (19.3 vs. 23.2 min) (P<0.05). Total sensory scores were significantly higher in the double stimulation group at 20 and 30 min after the block performance (P<0.05). Conclusions: Although the block performance time was longer in the double stimulation group, block onset time and extent of anesthesia were more favorable in the double stimulation group. [source]

Comparison of intrathecal magnesium, fentanyl, or placebo combined with bupivacaine 0.5% for parturients undergoing elective cesarean delivery

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2009
H. UNLUGENC
Background: Intrathecal (i.t.) administration of magnesium has been reported to potentiate opioid antinociception in rats and humans. In this prospective, randomized, double-blind, study, we investigated the sensory, motor, and analgesic block characteristics of i.t. magnesium 50 mg compared with fentanyl 25 ,g and saline when added to 0.5% bupivacaine (10 mg). Methods: Ninety ASA I or II adult patients undergoing cesarean section were randomly allocated to receive 1.0 ml of 0.9% sodium chloride in group S, 50 mg of magnesium sulfate (1.0 ml) 5% in group M, or 25 ,g of fentanyl (1.0 ml) in group F following 10 mg of bupivacaine 0.5% i.t. We recorded the following: onset and duration of sensory and motor block, maximal sensory block height, the time to reach the maximal dermatomal level of sensory block, and the duration of spinal anesthesia. Results: Magnesium did not shorten the onset time of sensory and motor blockade or prolong the duration of spinal anesthesia. The duration of sensory (P<0.032) and motor (P<0.002) blockade was significantly shorter in M and S groups than in the F group. The time to reach the maximal dermatomal level of sensory block was significantly shorter in the F group than in the S and M groups (P<0.002). Conclusion: In patients undergoing cesarean section with spinal anesthesia, the addition of magnesium sulfate (50 mg) i.t. to 10 mg of spinal bupivacaine (0.5%) did not shorten the onset time of sensory and motor blockade or prolong the duration of spinal anesthesia, as seen with fentanyl. [source]

Glycine Receptors Contribute to Hypnosis Induced by Ethanol

ALCOHOLISM, Issue 6 2009
Jiang H. Ye
Background:, Glycine is a major inhibitory neurotransmitter in the adult central nervous system (CNS), and its receptors (GlyRs) are well known for their effects in the spinal cord and the lower brainstem. Accumulating evidence indicates that GlyRs are more widely distributed in the CNS, including many supraspinal regions. Previous in vitro studies have demonstrated that ethanol potentiates the function of these brain GlyRs, yet the behavioral role of the brain GlyRs has not been well explored. Methods:, Experiments were conducted in rats. The loss of righting reflex (LORR) was used as a marker of the hypnotic state. We compared the LORR induced by systematic administration of ethanol and of ketamine in the absence and presence of the selective glycine receptor antagonist strychnine. Ketamine is a general anesthetic that does not affect GlyRs. Results:, Systemically administered (by intraperitoneal injection) ethanol and ketamine dose-dependently induced LORR in rats. Furthermore, systemically administered (by subcutaneous injection) strychnine dose-dependently reduced the percentage of rats exhibiting LORR induced by ethanol, increased the onset time, and decreased the duration of LORR. Strychnine had no effect, however, on the LORR induced by ketamine. Conclusions:, Given that hypnosis is caused by neuronal depression in upper brain areas, we therefore conclude that brain GlyRs contribute at least in part to the hypnosis induced by ethanol. [source]

Alterations in Circadian Rhythm Phase Shifting Ability in Rats Following Ethanol Exposure During the Third Trimester Brain Growth Spurt

ALCOHOLISM, Issue 5 2006
Hiromi Sakata-Haga
Background: Disruptions in sleep and feeding rhythms are among the consequences of prenatal alcohol exposure. Previously, we reported that ethanol exposure during the second trimester equivalent in rats produces long-lasting impairments in circadian system functioning. In the present study, we examined the effects of ethanol exposure during the third trimester equivalent brain growth spurt on the development of the circadian clock system. Methods: Sprague,Dawley male rat pups were exposed to 6.0 g/kg/d ethanol via an artificial rearing procedure on postnatal days (PD) 4 through 9 (EtOH). An artificially reared gastrostomized control group and a normally reared suckle control group were also included. At 10 to 12 weeks of age, wheel-running behavior was measured continuously under a 12-hour/12-hour light/dark (LD) cycle. Thereafter, subjects were exposed to a 6-hour phase delay of the LD cycle, and the ability to adjust to the new LD cycle was evaluated. Results: Before the phase delay, onset time of activity and acrophases of activity in all 3 groups were not significantly different from one another. After the 6-hour LD cycle delay, EtOH subjects were slower to adapt to the new cycle compared with both control groups, as measured by both activity onset and acrophase. Throughout the experiment, activity levels of EtOH subjects tended to be higher compared to both controls. Conclusions: These data demonstrate that ethanol exposure during the third trimester disrupts the ability to synchronize circadian rhythm to light cues. Disruptions in circadian regulation may cause abnormal behavioral rhythmicity, such as disrupted sleep and feeding patterns, as seen in individuals prenatally exposed to ethanol. [source]

Attribution of tumour lethality and estimation of the time to onset of occult tumours in the absence of cause-of-death Information

JOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 2 2000
H. Ahn
A new statistical approach is developed for estimating the carcinogenic potential of drugs and other chemical substances used by humans. Improved statistical methods are developed for rodent tumorigenicity assays that have interval sacrifices but not cause-of-death data. For such experiments, this paper proposes a nonparametric maximum likelihood estimation method for estimating the distributions of the time to onset of and the time to death from the tumour. The log-likelihood function is optimized using a constrained direct search procedure. Using the maximum likelihood estimators, the number of fatal tumours in an experiment can be imputed. By applying the procedure proposed to a real data set, the effect of calorie restriction is investigated. In this study, we found that calorie restriction delays the tumour onset time significantly for pituitary tumours. The present method can result in substantial economic savings by relieving the need for a case-by-case assignment of the cause of death or context of observation by pathologists. The ultimate goal of the method proposed is to use the imputed number of fatal tumours to modify Peto's International Agency for Research on Cancer test for application to tumorigenicity assays that lack cause-of-death data. [source]

Initiating and potentiating role of platelets in tissue factor-induced thrombin generation in the presence of plasma: subject-dependent variation in thrombogram characteristics

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2004
K. Vanschoonbeek
Summary., The hemostatic activity of plasma is determined by platelet activation and coagulation, which processes are mutually stimulatory. We studied this interaction by measuring the cleavage of fluorescent thrombin substrate in platelet-rich plasma (PRP), using the calibrated thrombogram method. In freshly isolated human plasma, thrombin formation triggered by tissue factor was fully dependent on the presence of platelets. It was abolished by annexin A5, indicating dependence on phosphatidylserine (PS) exposure at activated platelets. Comparison of plasmas from various subjects showed considerable interindividual variation in total amount of thrombin generation, regardless of whether platelets or PS-containing phospholipids were present. Integrin ,IIb,3 antagonists and ADP receptor blockage, but not aspirin, decreased the rate of thrombin generation (thrombin peak level) and extended the time of onset. Platelet inhibition with cAMP-elevating agents decreased the thrombin-forming rate, but surprisingly shortened the onset time. Stimulation of platelets with agonists of Gi/q-coupled receptors and, to a larger extent, with collagen or Ca2+ -ionophore increased the rate of thrombin generation and shortened its onset. In PRP from donors with low and high generation, platelet inhibitors and activators were similarly effective. Taken together, these results indicate that, in tissue factor-triggered PRP, PS exposure on activated platelets regulates both onset and rate of thrombin generation. However, coagulant activity rather than platelet activation determines the total amount of thrombin formed, i.e. the endogenous thrombin potential. Thus, kinetics of thrombin generation in PRP are controlled by platelet inhibitors and agonists, but the process is restricted in amount by the subject-dependent variation in coagulation. [source]

Time , size tradeoffs: a phylogenetic comparative study of flowering time, plant height and seed mass in a north-temperate flora

OIKOS, Issue 3 2008
Kjell Bolmgren
Parents face a timing problem as to when they should begin devoting resources from their own growth and survival to mating and offspring development. Seed mass and number, as well as maternal survival via plant size, are dependent on time for development. The time available in the favorable season will also affect the size of the developing juveniles and their survival through the unfavorable season. Flowering time may thus represent the outcome of such a time partitioning problem. We analyzed correlations between flowering onset time, seed mass, and plant height in a north-temperate flora, using both cross-species comparisons and phylogenetic comparative methods. Among perennial herbs, flowering onset time was negatively correlated with seed mass (i.e. plants with larger seeds started flowering earlier) while flowering onset time was positively correlated with plant height. Neither of these correlations was found among woody plants. Among annual plants, flowering onset time was positively correlated with seed mass. Cross-species and phylogenetically informed analyses largely agreed, except that flowering onset time was also positively correlated with plant height among annuals in the cross-species analysis. The different signs of the correlations between flowering onset time and seed mass (compar. gee regression coefficient=,7.8) and flowering onset time and plant height (compar. gee regression coefficient=+30.5) for perennial herbs, indicate that the duration of the growth season may underlie a tradeoff between maternal size and offspring size in perennial herbs, and we discuss how the partitioning of the season between parents and offspring may explain the association between early flowering and larger seed mass among these plants. [source]

Addition of sodium bicarbonate to lidocaine decreases the duration of peripheral nerve block in rat. (Harvard Medical School, Boston, MA) Anesthesiology 2000;93:1045,1052.

PAIN PRACTICE, Issue 2 2001
Catherine J. Sinnott
This study evaluated the effect of adding sodium bicarbonate to lidocaine with and without epinephrine versus equivalent alkalinization by sodium hydroxide (NaOH) on onset, degree, and duration of peripheral nerve block. The study was broken up into two parts. Part I examined alkalinization by sodium bicarbonate versus NaOH to pH 7.8 on 0.5% lidocaine, with and without epinephrine prepared from crystalline salt. Part II examined 0.5% and 1.0% commercial lidocaine solutions, with and without epinephrine, either unalkalinized or alkalinized with sodium bicarbonate or NaOH. The study concluded that with 1% commercial lidocaine without epinephrine, sodium bicarbonate decreases the degree and duration of the block. However, in solutions with epinephrine, sodium bicarbonate hastens onset, without effecting degree or duration. Comment by Octavio Calvillo, M.D., Ph.D. There is evidence that adding sodium bicarbonate to lidocaine without epinephrine improves the quality of epidural block, whereas adding sodium bicarbonate to lidocaine with epinephrine does not. The addition of 8.4% sodium bicarbonate to 2% lidocaine without epinephrine was shown to decrease the onset time and enhance the depth of the epidural block. When bicarbonate was added to 2% lidocaine with epinephrine neither onset time nor depth of the epidural block was affected. Most investigators have used epidural block as their paradigm. The authors in this study used the sciatic nerve block of the rat. [source]

Are peripheral and neuraxial blocks with ultrasound guidance more effective and safe in children?

PEDIATRIC ANESTHESIA, Issue 2 2009
KASIA RUBIN MD
Summary Background and aims:, The efficacy and safety of ultrasound guided (USG) pediatric peripheral nerve and neuraxial blocks in children have not been evaluated. In this review, we have looked at the success rate, efficacy and complications with USG peripheral nerve blocks and compared with nerve stimulation or anatomical landmark based techniques in children. Methods:, All suitable studies in MEDLINE, EMBASE Drugs and Cochrane Evidence Based Medicine Reviews: Cochrane Database of Systemic Reviews databases were identified. In addition, citation review and hand search of recent pediatric anesthesia and surgical journals were done. All three authors read all selected articles independently and a consensus was achieved. All randomized controlled trials (RCTs) comparing USG peripheral and neuraxial blocks with other techniques in children were included. Results:, Ultrasound guidance has been demonstrated to improve block characteristics in children including shorter block performance time, higher success rates, shorter onset time, longer block duration, less volume of local anesthetic agents and visibility of neuraxial structures. Conclusion:, Clinical studies in children suggest that US guidance has some advantages over more traditional nerve stimulation,based techniques for regional block. However, the advantage of US guidance on safety over traditional has not been adequately demonstrated in children except ilio-inguinal blocks. [source]

ORIGINAL ARTICLE: Optimal timing for the administration of intranasal dexmedetomidine for premedication in children

ANAESTHESIA, Issue 9 2010
V. M. Yuen
Summary Previous studies have shown that 1 ,g.kg,1 intranasal dexmedetomidine produces significant sedation in children aged between 2 and 12 years. This investigation was designed to evaluate the onset time. One hundred children aged 1,12 years of ASA physical status 1,2 undergoing elective surgery were randomly allocated to five groups. Patients in groups A to D received intranasal dexmedetomidine 1 ,g.kg,1. Patients in Group E received intranasal placebo (0.9% saline). Children from groups A, B, C, D and E had intravenous cannulation attempted at 30, 45, 60, 75 and 45 min respectively after intranasal drug or placebo administration. Vital signs, behaviour and sedation status of the children were assessed regularly until induction of anaesthesia. More children from groups A to D achieved satisfactory sedation at the time of cannulation when compared to group E (p < 0.001). The proportion of children who achieved satisfactory sedation was not significantly different among groups A to D. Overall 62% of the children who received intranasal dexmedetomidine had satisfactory sedation at the time of cannulation. The median (95% CI) time for onset of sedation was 25 (25,30) min. The median (95% CI) duration of sedation was 85 (55,100) min. [source]

Ultrasonographic guided axillary plexus blocks with low volumes of local anaesthetics: a crossover volunteer study

ANAESTHESIA, Issue 3 2010
P. Marhofer
Summary Our study group recently evaluated an ED95 local anaesthetic volume of 0.11 ml.mm,2 cross-sectional nerve area for the ulnar nerve. This prospective, randomised, double-blind crossover study investigated whether this volume is sufficient for brachial plexus blocks at the axillary level. Ten volunteers received an ultrasonographic guided axillary brachial plexus block either with 0.11 (,low' volume) or 0.4 (,high' volume) ml.mm,2 cross-sectional nerve area with mepivacaine 1%. The mean (SD) volume was in the low volume group 4.0 (1.0) and 14.8 (3.8) ml in the high volume group. The success rate for the individual nerve blocks was 27 out of 30 in the low volume group (90%) and 30 out of 30 in the high volume group (100%), resulting in 8 out of 10 (80%) vs 10 out of 10 (100%) complete blocks in the low vs the high volume groups, respectively (NS). The mean (SD) sensory onset time was 25.0 (14.8) min in the low volume group and 15.8 (6.8) min in the high volume group (p < 0.01). The mean (SD) duration of sensory block was 125 (38) min in the low volume group and 152 (70) min in the high volume group (NS). This study confirms our previous published ED95 volume for mepivacaine 1% to block peripheral nerves. The volume of local anaesthetic has some influence on the sensory onset time. [source]

Speed of onset of ,corner pocket supraclavicular' and infraclavicular ultrasound guided brachial plexus block: a randomised observer-blinded comparison

ANAESTHESIA, Issue 7 2009
M. J. Fredrickson
Summary This prospective, randomised, observer blinded study compared the onset time of brachial plexus block using 2% lidocaine 25,30 ml with adrenaline 5 ,g.ml,1 into the ,corner pocket' inferolateral/lateral to the subclavian artery (supraclavicular, n = 30) or to a triple point injection around the axillary artery (infraclavicular, n = 30). Mean (SD) onset time for complete pinprick sensory blockade assessed by a blinded observer in all four distal nerves was similar in both groups: supraclavicular = 22 (9.4) min, infraclavicular = 21 (7.1) min, p = 0.59. Complete sensory blockade in all four nerve territories at 30 min was achieved in 57% in group supraclavicular and 70% in group infraclavicular (p = 0.28). Painless surgery without the requirement for block supplementation was higher in group infraclavicular (28/30, 93%) compared with group supraclavicular (19/30, 67%; p = 0.01). Of the 11 failures in group supraclavicular, nine were due to incomplete ulnar nerve territory anaesthesia. These results do not support the concept of rapid onset successful supraclavicular block via a simple ultrasound-guided local anaesthetic injection inferolateral to the subclavian artery. [source]

Ultrasound vs nerve stimulation multiple injection technique for posterior popliteal sciatic nerve block

The use of low dose plain solutions of local anaesthetic agents for spinal anaesthesia in the prone position: bupivacaine compared with levobupivacaine

ANAESTHESIA, Issue 1 2009
O. Cuvas
Summary In this study, we aimed to test the hypothesis that 1-ml plain solution of 0.5% bupivacaine or 0.5% levopubivacaine administered in a subarachnoid block can provide adequate anaesthesia and operating conditions for pilonidal cyst/sinus operations performed in the prone position. There were no significant differences between the two groups in terms of patient demographic data, duration of operation, patient-surgeon satisfaction, haemodynamic changes and side effects. There were no significant differences found in the onset time, highest block level achieved, two segment regression, time to S2 regression of sensory block and the number of anaesthetised dermatomes, between the two groups (p = 0.077, 0.057, 0.091, 0.084 and 0.057 respectively). The incidence of complete motor blockade was 16% and 8% in Group B at the start and at the end of the operation. There was no complete motor blockade in Group L (p = 0.110 and 0.490 respectively). We conclude that both regimens are effective and safe for use in subarachnoid anaesthesia for pilonidal cyst/sinus operations performed in the prone position. [source]

Significance of the injection timing of ephedrine to reduce the onset time of rocuronium

ANAESTHESIA, Issue 8 2008
D. W. Han
Summary We postulated that the onset time of rocuronium can be accelerated effectively if it is administered at the time when the effect of ephedrine on cardiac output has reached its maximum. Seventy-five male, anaesthetised, patients were randomly allocated to three groups. Ephedrine 70 ,g.kg,1 was administered at 4 min (Early) or 30 s (Late) before administering rocuronium. The control group received saline at 4 min and at 30 s before rocuronium. The onset time of rocuronium in the Early group was significantly shorter than in the Control group, but there was no difference in the onset time between the Late and Control groups. There were no significant differences in the intubating conditions of the three groups. Ephedrine 70 ,g.kg,1 can reduce the onset time of rocuronium effectively if rocuronium is administered at 4 min following the ephedrine injection, when the effect of ephedrine on cardiac output is expected to reach its maximum. [source]

Sodium imaging intensity increases with time after human ischemic stroke,

ANNALS OF NEUROLOGY, Issue 1 2009
Muhammad S. Hussain MD
Objective Establishing time of onset is important in acute stroke management. Current imaging modalities do not allow determination of stroke onset time. Although correlations between sodium magnetic resonance imaging signal intensity within ischemic lesions and time of onset have been shown in animal models, the relation to onset time has not been established in human stroke. Utilizing high-quality sodium images, we tested the hypothesis that sodium signal intensity increases with time from symptom onset in human ischemic stroke. Methods Twenty-one stroke patients (63 ± 15 years old) were scanned 4 to 104 hours after symptom onset. Follow-up images were obtained in 10 patients at 23 to 161 hours after onset, yielding a total of 32 time points. A standard stroke imaging protocol was acquired at 1.5 Tesla, followed by sodium magnetic resonance imaging at 4.7 Tesla. Relative sodium signal intensity within each lesion was measured with respect to the contralateral side. Results The sodium image quality was sufficient to visualize each acute lesion (lesion volume range, 1.7,217cm3). Relative sodium signal intensity increased nonlinearly over time after stroke onset. Sodium images acquired within 7 hours (n = 5) demonstrated a relative increase in lesion intensity of 10% or less, whereas the majority beyond 9 hours demonstrated increases of 23% or more, with an eventual leveling at 69 ± 18%. Interpretation Increases of sodium signal intensity within the ischemic lesion are related to time after stroke onset. Thus, noninvasive imaging of sodium may be a novel metabolic biomarker related to stroke progression. Ann Neurol 2009;66:55,62 [source]

Sequence of Electrocardiographic and Acoustic Cardiographic Changes and Angina during Coronary Occlusion and Reperfusion in Patients Undergoing Percutaneous Coronary Intervention

ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2009
A.N.P., Eunyoung Lee R.N., Ph.D.
Background: Previous studies have suggested that ventricular function may be impaired without or prior to electrocardiographic changes or angina during ischemia. Understanding of temporal sequence of electrical and functional ischemic events may improve the detection of myocardial ischemia. Methods: A prospective study was performed in 21 subjects undergoing percutaneous coronary intervention (PCI) who had both ST amplitude changes >2 standard deviations above baseline on 12-lead electrocardiography (ECG), and new or increased third or fourth heart sound (S3 or S4) intensity measured by computerized acoustic cardiography. The sequence of the onset and resolution of these signs of ischemia were examined following coronary balloon inflation and deflation. Results: Electrocardiographic ST amplitude and diastolic heart sound changes occurred contemporaneously, shortly after coronary occlusion (mean onset from balloon inflation; ST changes, 21 ± 17 seconds; S4, 25 ± 26 seconds; S3, 45 ± 43 seconds). In 40% of patients, a new or increased S3 or S4 developed earlier than ST changes. Anginal symptoms occurred in only 2 of the 21 subjects during ischemia with a mean onset time of 68 seconds. ST-segment changes resolved earliest (33 seconds after balloon deflation) while diastolic heart sounds (89 ± 146 seconds) and angina (586 ± 653 seconds) resolved later. Conclusion: A new or intensified S3 and/or S4 occurred contemporaneously with electrocardiographic changes during ischemia. These diastolic heart sounds persisted longer than ST changes following coronary reperfusion. Acoustic cardiographic assessment of diastolic heart sounds may aid in the early detection of myocardial ischemia, particularly in those patients with an uninterpretable ECG. [source]

Joint Modeling for Cognitive Trajectory and Risk of Dementia in the Presence of Death

BIOMETRICS, Issue 1 2010
Binbing Yu
Summary Dementia is characterized by accelerated cognitive decline before and after diagnosis as compared to normal aging. It has been known that cognitive impairment occurs long before the diagnosis of dementia. For individuals who develop dementia, it is important to determine the time when the rate of cognitive decline begins to accelerate and the subsequent gap time to dementia diagnosis. For normal aging individuals, it is also useful to understand the trajectory of cognitive function until their death. A Bayesian change-point model is proposed to fit the trajectory of cognitive function for individuals who develop dementia. In real life, people in older ages are subject to two competing risks, e.g., dementia and dementia-free death. Because the majority of people do not develop dementia, a mixture model is used for survival data with competing risks, which consists of dementia onset time after the change point of cognitive function decline for demented individuals and death time for nondemented individuals. The cognitive trajectories and the survival process are modeled jointly and the parameters are estimated using the Markov chain Monte Carlo method. Using data from the Honolulu Asia Aging Study, we show the trajectories of cognitive function and the effect of education, apolipoprotein E 4 genotype, and hypertension on cognitive decline and the risk of dementia. [source]