bluuebunny/crossref_metadata_2025 huggingface dataset:
Memory beyond the synapse
Authors: ROSE STEVEN P.R.
Published: June 2005

Based on studies of the molecular and cellular cascades that occur during memory consolidation for a one-trial passive-avoidance learning task in the young chick, I review the evidence that memory is encoded in permanent changes in synaptic connectivity in a specific brain region, the Hebb hypothesis. I conclude that despite the fact that such a cascade occurs, culminating in the synthesis of cell-adhesion molecules that are involved in synaptic remodelling, synaptic events are not in themselves sufficient to account for the phenomena of memory. Both whole brain (neuromodulator) and whole body (hormonal) processes are engaged. Memories are labile, disarticulated and stored in a distributed manner; how the mind/brain recreates coherent memories from this pattern is a mystery.
Spironolactone and its main metabolite canrenoic acid block hKv1.5, Kv4.3 and Kv7.1+minK channels
Authors: Gómez Ricardo , Núñez Lucía , Caballero Ricardo , Vaquero Miguel , Tamargo Juan , Delpón Eva
Published: June 2005

Both spironolactone (SP) and its main metabolite, canrenoic acid (CA), prolong cardiac action potential duration and decrease the Kv11.1 (HERG) current. We examined the effects of SP and CA on cardiac hKv1.5, Kv4.3 and Kv7.1+minK channels that generate the human IKur, Ito1 and IKs, which contribute to the control of human cardiac action potential duration.

hKv1.5 currents were recorded in stably transfected mouse fibroblasts and Kv4.3 and Kv7.1+minK in transiently transfected Chinese hamster ovary cells using the whole‐cell patch clamp.

SP (1 μM) and CA (1 nM) inhibited hKv1.5 currents by 23.2±3.2 and 18.9±2.7%, respectively, shifted the midpoint of the activation curve to more negative potentials and delayed the time course of tail deactivation.

SP (1 μM) and CA (1 nM) inhibited the total charge crossing the membrane through Kv4.3 channels at +50 mV by 27.1±6.4 and 27.4±5.7%, respectively, and accelerated the time course of current decay. CA, but not SP, shifted the inactivation curve to more hyperpolarised potentials (Vh−37.0±1.8 vs −40.8±1.6 mV, n=10, P<0.05).

SP (10 μM) and CA (1 nM) also inhibited Kv7.1+minK currents by 38.6±2.3 and 22.1±1.4%, respectively, without modifying the voltage dependence of channel activation. SP, but not CA, slowed the time course of tail current decay.

CA (1 nM) inhibited the IKur (29.2±5.5%) and the Ito1 (16.1±3.9%) recorded in mouse ventricular myocytes and the IK (21.8±6.9%) recorded in guinea‐pig ventricular myocytes.

A mathematical model of human atrial action potentials demonstrated that K+ blocking effects of CA resulted in a lengthening of action potential duration, both in normal and atrial fibrillation simulated conditions.

The results demonstrated that both SP and CA directly block hKv1.5, Kv4.3 and Kv7.1+minK channels, CA being more potent for these effects. Since peak free plasma concentrations of CA ranged between 3 and 16 nM, these results indicated that blockade of these human cardiac K+ channels can be observed after administration of therapeutic doses of SP.

Blockade of these cardiac K+ currents, together with the antagonism of the aldosterone proarrhythmic effects produced by SP, might be highly desirable for the treatment of supraventricular arrhythmias.

British Journal of Pharmacology (2005) 146, 146–161. doi:10.1038/sj.bjp.0706302
A new method on recycling coefficient measurement using impurity pellet injection in a large helical device
Authors: Nozato Hideaki , Morita Shigeru , Goto Motoshi ,   LHD Experimental Group
Published: June 2005

Recycling coefficients of carbon, aluminum, and titanium were evaluated using a new technique combining impurity pellet injection with high-spatial resolution bremsstrahlung measurement in hydrogen and helium plasmas on the large helical device. The recycling coefficient of impurities was investigated by measuring absolute intensities with the visible bremsstrahlung array. The time evolution of the bremsstrahlung signals was modeled by an impurity transport code adjusting the diffusion coefficient, convective velocity, and recycling coefficient. As a result, a finite value of the recycling coefficient was required in the case of carbon, whereas aluminum and titanium were explained as nonrecycled particles. It was also clarified that the recycling coefficient of carbon had a larger value in hydrogen plasmas (R=0.5–0.65) than in helium plasmas (R=0–0.2), suggesting the formation of hydrogen molecules.
The city and the bush—partnerships to reverse the population decline in Australia's Wheatbelt
Authors: Newman Peter
Published: June 2005

Major trends that are draining people from the Wheatbelt are globalisation of the economy (and its associated global urban culture) and coastalisation based on lifestyle preferences. A focus on Wheatbelt towns in partnership with the adjacent global city is needed to reverse the decline. It will require a new quality of life attraction similar to that drawing people to the coast, a stronger sense of place, and greater social diversity. It will also require tapping of new global city sustainability obligations through partnerships between the city and its bioregion on issues of biodiversity, new bioindustries, and new water regimes, and clear planning to contain sprawl in the city and coasts. Hope for rejuvenation can be provided through the example of inner city areas, which suffered similar problems of decline, and reversed them over a 30-year period.
Development of a sensory protocol for testing palatability of sheep meats
Authors: Thompson J. M. , Gee A. , Hopkins D. L. , Pethick D. W. , Baud S. R. , O'Halloran W. J.
Published: June 2005

A total of 108 grill and 108 roast samples were prepared from lamb (n = 10) and mutton (n = 8) carcasses for sensory testing using a consumer taste panel. Grill and roast samples were prepared from the left and right sides of the carcass, respectively, using longissimus, biceps femoris, gluteus medius, serratus ventralis and semimembranosus. Due to size constraints, muscle from both sides was used to form grill samples for the vastus lateralis, and roast samples from the triceps brachii. Grill and roast samples were sensory tested using 360 untrained consumers. Each consumer was given a total of 6 experimental samples and each sample was tested by 10 different consumers.
Sensory scores for tenderness, juiciness, like flavour and overall liking from both the grilled and roasted samples were highly correlated (P<0.05). For grilling, the different muscles were correlated for tenderness and overall liking scores (P<0.05), with the exception of the semimembranosus (P>0.05). In contrast, juiciness and like flavour scores were poorly correlated between grilled muscles. For the roasted samples, sensory scores were generally uncorrelated between muscles. The statistical significance of the age category and muscle effects was greater in grill samples, but stimulation effects were of similar significance using either cooking method. It was proposed that roasting reduced treatment effects that affected sensory via differences in connective tissue toughness, due to gelatinisation of connective tissue during cooking. For testing production and processing effects on palatability, grilling was more sensitive for detecting treatment effects, than roasting.
Comparative ecology of two co-occurring floodplain plants: the native Sporobolus mitchellii and the exotic Phyla canescens
Authors: Taylor Ben , Ganf George G.
Published: June 2005

In the northern Murray–Darling Basin (MDB), Australia, the displacement of native floodplain grasses by Phyla canescens (Lippia), an exotic herb, coincided with a reduced frequency of floodplain inundation owing to river regulation. Although river regulation and P. canescens occur in the southern MDB, P. canescens abundance has not increased significantly since 1988. This work reports on the current distribution of P. canescens and the native grass Sporobolus mitchellii on the lower River Murray. It demonstrates that there are significant differences in the edaphic characteristics of sites occupied by the two species and co-occurrence is rare. To explain this observation, two factors were investigated: the resilience of S. mitchellii to invasion by P. canescens and the response of both species to artificial spring floods. At initial densities of >25%, S. mitchellii exhibited strong resilience to invasion by P. canescens. The growth response of both species to spring floods was similar. However, P. canescens reproduced asexually when inundated and, on exposure, exhibited a root distribution that would enhance its capacity to survive future droughts. In contrast, S. mitchellii was more tolerant of low soil moisture than P. canescens. The re-introduction of spring floods could favour the expansion of P. canescens.
Extracellular phosphatase activity of freshwater phytoplankton exposed to different in situ phosphorus concentrations
Authors: Ŝtrojsová A. , Vrba J. , Nedoma J. , Ŝimek K.
Published: June 2005

Extracellular phosphatase production and biomass change were investigated in phytoplankton species transplanted from the phosphorus-limited dam area of a eutrophic reservoir and exposed to the phosphorus-sufficient inflow part and vice versa. Extracellular phosphatase activity was studied using the enzyme-labelled fluorescence (ELF) technique, allowing for direct microscopic detection of enzyme activity and, moreover, its quantification using image cytometry. Several phytoplankton species (e.g. Anabaena planctonica, Microcystis aeruginosa, Fragilaria crotonensis, Ankyra ancora and Planktosphaeria gelatinosa) regulated phosphatase activity according to external phosphorus concentration. On the contrary, picocyanobacteria and several green algae (Coelastrum microporum, Crucigeniella sp., Pediastrum tetras, and Staurastrum planctonicum) did not produce extracellular phosphatases at all. The species-specific extracellular phosphatase activity of F. crotonensis, A. ancora, and P. gelatinosa ranged between 0.02 and 3.5 fmol μm−2 h−1.
The pro-fusion domain of herpes simplex virus glycoprotein D (gD) interacts with the gD N terminus and is displaced by soluble forms of viral receptors
Authors: Fusco Daniela , Forghieri Cristina , Campadelli-Fiume Gabriella
Published: June 2005

Entry of herpes simplex virus into the cell requires the interaction of gD with one of its receptors, herpesvirus entry mediator or nectin 1, and the intervention of gB, gH, or gL, required to execute fusion of the virion envelope with cell membranes. The gD ectodomain is organized in two structurally and functionally differentiated regions. The N terminus (residues 1-260) carries the receptor binding sites, and the C terminus (residues 260-310) functions as the pro-fusion domain (PFD), which is required for viral infectivity and fusion but not for receptor binding. The objective of our studies is to elucidate how gD links receptor recognition to the triggering of fusion. Here, we show that PFD is made of subdomains 1 and 2 (amino acids 260-285 and 285-310). Each one partially contributed to herpes simplex virus infectivity. By means of glutathione
S
-transferase (GST) fusion proteins, we show that PFD bound soluble forms of gD, truncated at residue 260 (gD
260t
) or downstream. Both PFD subdomains bound gD
260t
, highlighting multiple contact sites between the N and C termini of gD. When gD
260t
was in complex with either receptor, it failed to bind GST-PFD. In turn, the receptors did not bind GST-PFD, irrespective of whether they were in complex with gD. Thus, gD
260t
interacted with the C terminus only if unbound to the receptor. We propose that (
i
) before receptor binding, gD adopts a “closed” conformation in which the N and C termini interact; and (
ii
) on encounter with a receptor, gD modifies its conformation and the N and C termini are released from reciprocal interactions (“opened” conformation) and enabled to trigger fusion.
Sympathetic and Hemodynamic Effects of Moderate and Deep Sedation with Propofol in Humans
Authors: Ebert Thomas J.
Published: June 2005

Background

The objective of this study was to determine the mechanisms involved in the hypotension associated with sedative doses of propofol in humans.

Methods

Ten healthy volunteers (aged 21-37 yr) participated on two occasions and in random order received placebo or propofol infusions. Standard monitoring and radial artery blood pressure were combined with measurement of forearm blood flow (plethysmography) and derivation of forearm vascular resistance, recording of peroneal nerve sympathetic activity, and blood sampling for norepinephrine concentrations. A computer-controlled infusion pump delivered placebo or two concentrations of propofol, adjusted to achieve moderate and deep sedation based on the Observer Assessment of Alertness/Sedation score (responsiveness component) of 4 and 3. Level of sedation was quantitated using bispectral analysis of the electroencephalogram. Baroreflexes were assessed with a hypotensive challenge via administration of sodium nitroprusside.

Results

Baseline neurocirculatory and respiratory parameters did not differ between sessions. Progressive infusions to achieve moderate and deep sedation resulted in average Bispectral Index values of 70 and 54, respectively. Propofol significantly reduced sympathetic nerve activity at both levels of sedation and decreased norepinephrine and forearm vascular resistance at deep sedation. These effects resulted in significant decreases in mean blood pressure of 9% and 18% at moderate and deep sedation, respectively. Propofol also reduced reflex increases in sympathetic nerve activity.

Conclusions

These data from healthy subjects indicate that sedation doses of propofol, which did not compromise respiratory function, had substantial inhibitory effects on sympathetic nerve activity and reflex responses to hypotension resulting in vasodilation and significant decreases in mean blood pressure.
Management of the Difficult Airway
Authors: Peterson Gene N. , Domino Karen B. , Caplan Robert A. , Posner Karen L. , Lee Lorri A. , Cheney Frederick W.
Published: June 2005

Background

The purpose of this study was to identify the patterns of liability associated with malpractice claims arising from management of the difficult airway.

Methods

Using the American Society of Anesthesiologists Closed Claims database, the authors examined 179 claims for difficult airway management between 1985 and 1999 where a supplemental data collection tool was used and focused on airway management, outcomes, and the role of the 1993 Difficult Airway Guidelines in litigation. Chi-square tests and multiple logistic regression analysis compared risk factors for death or brain damage (death/BD) from two time periods: 1985-1992 and 1993-1999.

Results

Difficult airway claims arose throughout the perioperative period: 67% upon induction, 15% during surgery, 12% at extubation, and 5% during recovery. Death/BD with induction of anesthesia decreased in 1993-1999 (35%) compared with 1985-1992 (62%; P < 0.05; odds ratio, 0.26; 95% confidence interval, 0.11-0.63; P = 0.003). In contrast, death/BD associated with other phases of anesthesia did not significantly change over the time periods. The odds of death/BD were increased by the development of an airway emergency (odds ratio, 14.98; 95% confidence interval, 6.37-35.27; P < 0.001). During airway emergencies, persistent intubation attempts were associated with death/BD (P < 0.05). Since 1993, the Airway Guidelines were used to defend care (8%) and criticize care (3%).

Conclusions

Death/BD in claims from difficult airway management associated with induction of anesthesia but not other phases of anesthesia decreased in 1993-1999 compared with 1985-1992. Development of additional management strategies for difficult airways encountered during maintenance, emergence, or recovery from anesthesia may improve patient safety.
Role of Endothelial Nitric Oxide Synthase as a Trigger and Mediator of Isoflurane-induced Delayed Preconditioning in Rabbit Myocardium
Authors: Chiari Pascal C. , Bienengraeber Martin W. , Weihrauch Dorothee , Krolikowski John G. , Kersten Judy R. , Warltier David C. , Pagel Paul S.
Published: June 2005

Background

Isoflurane produces delayed preconditioning in vivo. The authors tested the hypothesis that endothelial, inducible, or neuronal nitric oxide synthase (NOS) is a trigger or mediator of this protective effect.

Methods

In the absence or presence of exposure to isoflurane (1.0 minimum alveolar concentration) 24 h before experimentation, pentobarbital-anesthetized rabbits (n = 128) instrumented for hemodynamic measurement received 0.9% saline (control), the nonselective NOS inhibitor N-nitro-l-arginine methyl ester (10 mg/kg), one of two of the selective inducible NOS antagonists aminoguanidine (300 mg/kg) or 1400W (0.5 mg/kg), or the selective neuronal NOS inhibitor 7-nitroindazole (50 mg/kg) administered before exposure to isoflurane (trigger; day 1) or left anterior descending coronary artery occlusion (mediator; day 2). All rabbits underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Tissue samples for reverse-transcription polymerase chain reaction and immunohistochemistry were also obtained in the presence or absence of N-nitro-l-arginine methyl ester with or without isoflurane pretreatment.

Results

Isoflurane significantly (P < 0.05) reduced infarct size (23 +/- 5% [mean +/- SD] of the left ventricular area at risk; triphenyltetrazolium chloride staining) as compared with control (42 +/- 7%). N-nitro-l-arginine methyl ester administered before isoflurane or coronary occlusion abolished protection (49 +/- 7 and 43 +/- 10%, respectively). Aminoguanidine, 1400W, and 7-nitroindazole did not alter infarct size or affect isoflurane-induced delayed preconditioning. Isoflurane increased endothelial but not inducible NOS messenger RNA transcription and protein translation immediately and 24 h after administration of the volatile agent. Pretreatment with N-nitro-l-arginine methyl ester attenuated isoflurane-induced increases in endothelial NOS expression.

Conclusions

The results suggest that endothelial NOS but not inducible or neuronal NOS is a trigger and mediator of delayed preconditioning by isoflurane in vivo.
Neuroprotective Effect of Epidural Electrical Stimulation against Ischemic Spinal Cord Injury in Rats
Authors: Kakinohana Manabu , Harada Hideki , Mishima Yasunori , Kano Tatsuhiko , Sugahara Kazuhiro
Published: June 2005

Background

Electroconvulsion therapy is likely to serve as an effective preconditioning stimulus for inducing tolerance to ischemic brain injury. The current study examines whether electrical stimuli on the spinal cord is also capable of inducing tolerance to ischemic spinal cord injury by transient aortic occlusion.

Methods

Spinal cord ischemia was induced by occlusion of the descending thoracic aorta in combination with maintaining systemic hypotension (40 mmHg) during the procedure. Animals implanted with epidural electrodes were divided into four groups according to electrical stimulation and sham. Two groups consisted of rapid preconditioning (RE group, n = 8) and sham procedure (RC group, n = 8) 30 min before 9 min of spinal cord ischemia. In the two groups that underwent delayed preconditioning, rats were exposed to 9 min of aortic occlusion 24 h after either pretreatment with epidural electrical stimulation (DE group, n = 8) or sham (DC group, n = 8). In addition, rats were exposed to 6-11 min of spinal cord ischemia at 30 min or 24 h after epidural electrical stimulation or sham stimulation. The group P50 represents the duration of spinal cord ischemia associated with 50% probability of resultant paraplegia.

Results

Pretreatment with electrical stimulation in the DE group but not the RE group protected the spinal cord against ischemia, and this stimulation prolonged the P50 by approximately 15.0% in the DE group compared with the DC group.

Conclusions

Although the optimal setting for this electrical preconditioning should be determined in future studies, the results suggest that epidural electrical stimulation will be a useful approach to provide spinal protection against ischemia.
Differential Inhibition of Neuronal Na+–Ca2+Exchange versus Store-operated Ca2+Channels by Volatile Anesthetics in Pheochromocytoma (PC12) Cells
Authors: Ay Binnaz , Wallace Daniel , Mantilla Carlos B. , Prakash Yedotore S.
Published: June 2005

Background

Ca2+ influx is a key component of neuronal intracellular Ca2+ ([Ca2+]i) regulation. The authors hypothesized that volatile anesthetic inhibition of neuronal activity is mediated by inhibition of Ca2+ influx via two major mechanisms: plasma membrane Na+-Ca2+ exchange (NCX) and the novel mechanism of Ca2+ influx triggered by endoplasmic reticulum Ca2+ depletion (store-operated Ca2+ channels [SOCCs]).

Methods

Differentiated rat pheochromocytoma cells loaded with the Ca2+ indicator fura-2 were Na+-loaded with 0 Ca2+, 145 mm Na+ Tyrode's and 5 microm cyclopiazonic acid plus 10 microm ryanodine (functionally isolating plasma membrane). Influx-mode NCX was rapidly reactivated by 0 Na+ and 2.5 mm Ca2+. The protocol was repeated in the presence of volatile anesthetics (0.5-1.5 minimum alveolar concentration [MAC] halothane, isoflurane, or sevoflurane) or other drugs to characterize NCX. To examine SOCCs, endoplasmic reticulum Ca2+ was depleted by cyclopiazonic acid in 0 extracellular Ca2+, and Ca2+ influx was triggered by rapid reintroduction of extracellular Ca2+. The protocol was repeated in the presence of anesthetics or other drugs to characterize SOCCs.

Results

Influx via NCX was not inhibited by voltage-gated Ca2+ channel blockers but was sensitive to NCX inhibitors. Halothane and isoflurane (0.5-1.5 MAC) significantly inhibited NCX (P < 0.05; paired comparisons), whereas sevoflurane at less than 1.5 MAC did not inhibit NCX. SOCC-mediated Ca2+ influx was insensitive to a variety of Ca2+ channel blockers but was inhibited by Ni2+. Such influx was sensitive only to halothane at greater than 1 MAC but not isoflurane or sevoflurane.

Conclusions

These data indicate that volatile anesthetics, especially halothane and isoflurane, interfere with neuronal [Ca2+]i regulation by inhibiting NCX but not SOCC-mediated Ca2+ influx (except high concentrations of halothane).
Local Anesthetic Interaction with Human Ether-a-go-go –related Gene (HERG) Channels
Authors: Siebrands Cornelia C. , Schmitt Nicole , Friederich Patrick
Published: June 2005

Background

Human ether-a-go-go-related gene (HERG) potassium channels constitute a potential target involved in cardiotoxic side effects of amino-amide local anesthetics. The molecular interaction site of these low-affinity blockers with HERG channels is currently unknown. The aim of this study was to determine the effect of the mutations Y652A and F656A in the putative drug binding region of HERG on the inhibition by bupivacaine, ropivacaine, and mepivacaine.

Methods

The authors examined the inhibition of wild-type and mutant HERG channels, transiently expressed in Chinese hamster ovary cells by bupivacaine, ropivacaine, and mepivacaine. Whole cell patch clamp recordings were performed at room temperature.

Results

Inhibition of HERG wild-type and mutant channels by the different local anesthetics was concentration dependent, stereoselective, and reversible. The sensitivity decreased in the order bupivacaine > ropivacaine > mepivacaine for wild-type and mutant channels. The mutant channels were approximately 4-30 times less sensitive to the inhibitory action of the different local anesthetics than the wild-type channel. The concentration-response data were described by Hill functions (bupivacaine: wild-type IC50 = 22 +/- 2 microm, n = 38; Y652A IC50 = 95 +/- 5 microm, n = 31). The mutations resulted in a change of the stereoselectivity of HERG channel block by ropivacaine. The potency of the local anesthetics to inhibit wild-type and mutant channels correlated with the lipophilicity of the drug (r > 0.9).

Conclusions

These results indicate that local anesthetics specifically but not exclusively interact with the aromatic residues Y652 and F656 in S6 of HERG channels.
Alfentanil and Placebo Analgesia
Authors: Olofsen Erik , Romberg Raymonda , Bijl Hans , Mooren René , Engbers Frank , Kest Benjamin , Dahan Albert
Published: June 2005

Background

To assess whether patient sex contributes to the interindividual variability in alfentanil analgesic sensitivity, the authors compared male and female subjects for pain sensitivity after alfentanil using a pharmacokinetic-pharmacodynamic modeling approach.

Methods

Healthy volunteers received a 30-min alfentanil or placebo infusion on two occasions. Analgesia was measured during the subsequent 6 h by assaying tolerance to transcutaneous electrical stimulation (eight men and eight women) of increasing intensity or using visual analog scale scores during treatment with noxious thermal heat (five men and five women). Sedation was concomitantly measured. Population pharmacokinetic-pharmacodynamic models were applied to the analgesia and sedation data using NONMEM. For electrical pain, the placebo and alfentanil models were combined post hoc.

Results

Alfentanil and placebo analgesic responses did not differ between sexes. The placebo effect was successfully incorporated into the alfentanil pharmacokinetic-pharmacodynamic model and was responsible for 20% of the potency of alfentanil. However, the placebo effect did not contribute to the analgesic response variability. The pharmacokinetic-pharmacodynamic analysis of the electrical and heat pain data yielded similar values for the potency parameter, but the blood-effect site equilibration half-life was significantly longer for electrical pain (7-9 min) than for heat pain (0.2 min) or sedation (2 min).

Conclusions

In contrast to the ample literature demonstrating sex differences in morphine analgesia, neither sex nor subject expectation (i.e., placebo) contributes to the large between-subject response variability with alfentanil analgesia. The difference in alfentanil analgesia onset and offset between pain tests is discussed.
Topical 2% Amitriptyline and 1% Ketamine in Neuropathic Pain Syndromes
Authors: Lynch Mary E. , Clark Alexander J. , Sawynok Jana , Sullivan Michael J. L.
Published: June 2005

Background

A double-blind, randomized, placebo-controlled 3-week study evaluated the efficacy of topical 2% amitriptyline, 1% ketamine, and a combination of both in treating patients with neuropathic pain.

Methods

Ninety-two patients with diabetic neuropathy, postherpetic neuralgia, or postsurgical/posttraumatic neuropathic pain with allodynia, hyperalgesia, or pinprick hypesthesia were randomly assigned to receive one of four creams (placebo, 2% amitriptyline, 1% ketamine, or 2% amitriptyline-1% ketamine combined). The primary outcome measure was change in average daily pain intensity (baseline week vs. final week) using an 11-point numerical pain rating scale. Secondary outcomes included the McGill Pain Questionnaire, measures of allodynia and hyperalgesia, and patient satisfaction.

Results

A reduction in pain scores of 1.1-1.5 units was observed in all groups, and there was no difference between groups. Blood concentrations revealed no significant systemic absorption. Minimal side effects were encountered.

Conclusion

This randomized, placebo-controlled trial examining topical 2% amitriptyline, 1% ketamine, and a combination in the treatment of neuropathic pain revealed no difference between groups. Optimization of doses may be required, because another study has revealed that higher concentrations of these agents combined do produce significant analgesia.
Sex- and Age-related Differences in Morphine Requirements for Postoperative Pain Relief
Authors: Aubrun Frédéric , Salvi Nadège , Coriat Pierre , Riou Bruno
Published: June 2005

Background

Sex-related differences in the perception of pain and susceptibility to opioids remain a matter of debate. Intravenous morphine titration used to obtain pain relief in the immediate postoperative period is a unique clinical model for assessing the effect of sex on reported pain. Because of the wide variation in dose requirements for pain management, the authors conducted a prospective study in a large population and also assessed the effect of aging.

Methods

Intravenous morphine titration was administered as a bolus of 2 (body weight  60 kg) during the immediate postoperative period. The interval between each bolus was 5 min. The visual analog pain scale (VAS) threshold required to administer morphine was 30, and pain relief was defined as a VAS score of 30 or less. Data are expressed as mean +/- SD.

Results

Data from 4,317 patients were analyzed; 54% of the patients were male, and 46% were female. The mean morphine dose required to obtain pain relief was 11.9 +/- 6.8 mg or 0.173 +/- 0.103 mg/kg. Women had a higher initial VAS score (74 +/- 19 vs. 71 +/- 19; P < 0.001) and required a greater dose of morphine (0.183 +/- 0.111 vs. 0.165 +/- 0.095 mg/kg; P < 0.001). In contrast, no significant difference was noted in elderly (aged > 75 yr) patients (0.163 +/- 0.083 vs. 0.157 +/- 0.085 mg/kg).

Conclusion

Women experienced more severe postoperative pain and required a greater dose (+11%) of morphine than men in the immediate postoperative period. This sex-related difference disappeared in elderly patients.
The high‐temperature oxidation resistance of thin‐walled ingots of Ni3Al alloys with directional grain structure
Authors: Verin A.S. , Verin M.A.
Published: June 2005

Purpose

This paper describes the changing of high‐temperature oxidation resistance (HTOR) at the temperature 1,200°C which is dependant on characteristics of alloying and microstructure. The aim of the research was to show a broad problem of using the intermetallic Ni3Al in the production of propulsion aircraft engines because this material has a very high HTOR and low density.

Design/methodology/approach

For the estimation of a level of HTOR of Ni3Al (Ni‐12Al) and its alloying compositions, a method was used in which samples were heated in ambient atmosphere at 1,200°C for a period of 1,500 h. The samples were weighed every 100 h. The data was obtained for eight different compositions.

Findings

The process of researching indicated that a maximum HTOR has the composition Ni‐12Al without alloying which is obtaining by dosed directional solidification (DDS) method and having the largest structural stability at 1,200°C.

Practical implications

This material is broadly used in the production of valves, electrical heaters, etc. However, these details are obtained by equiaxial casting or powder metallurgy methods. The material obtained by DDS method has higher strength characteristics and may be implicated in many components of aircraft engines (elements of the firing chamber or a stationary blades, etc.).

Originality/value

This research presents a new type of microstructure which has a matrix Ni3Al on a base of disordered gamma phase (DDS Method). Currently, this structure has had little studies carried out on it. However, it could become an object for detailed research for process phase precipitation using a super high magnifications.
Neoclassicism, artificial intelligence, and the marginalization of ethics
Authors: Davis John B.
Published: June 2005

Purpose

The paper examines the dependence of the positivist and welfarist preference satisfaction paradigm of neoclassical economics upon an implicit functionalist philosophy of mind. Functionalism is the doctrine that mental states are strictly materialistic and understandable in cause‐effect terms. An important aspect of functionalism is the multiple realizability thesis, namely, that mental states can be realized in any type of hardware, whether human brain or computer.

Design/methodology/approach

The approach used involves investigating the fact‐value distinction after Robbins in terms of the positivist meta‐ethical view known as emotivism, and then explaining emotivism as inherently functionalist. Functionalist thinking itself is explained in terms of contemporary philosophy of mind.

Findings

An important finding is that the preference satisfaction paradigm can be shown to be as suitable to artificial intelligence systems as to human beings. A consequence of this is that normative concerns are increasingly difficult to address in connection with the neoclassical thinking about economic agents.

Research limitations/implications

The paper does not investigate more recent research programs in economics (such as behavioural economics) that depart from basic neoclassical assumptions.

Practical implications

A practical implication of the paper is that it shifts attention to previously un‐emphasized aspects of neoclassical thinking.

Originality/value

The paper's value to explain the relation of economics to ethics in neoclassical economics in connection with functionalist philosophy of mind.
An improved two‐tiered strategy to intrusion detection
Authors: Sodiya A.S. , Longe H.O.D.
Published: June 2005

Purpose

A work that combined strategies in designing anomaly‐based instruction detection system (IDS) was described in CSIDS. This new work seeks to improve on CSIDS.

Design/methodology/approach

The shortcomings of CSIDS were first identified and critically analysed. An improved approach for combining data mining and expert system is then presented and implemented.

Findings

The result of the evaluation of the new design produced a better result in terms of the detection efficiency and false alarm rate.

Research limitations/implications

It might be necessary to use data from diverse environments to test the design. However, it was effectively shown that an IDS that combines strategies has been designed.

Practical implications

This work discusses the technical issues of IDS and will motivate researchers in IDS. It has also shown how strategies could be combined for effective intrusion detection.

Originality/value

This paper resulted from the existing problems in IDS and presents practical information in intrusion detection. It is definitely a tool needed by researchers in IDS.
Chemical exposure and symptoms of hand dermatitis in construction painters
Authors: Kaukiainen Ari , Riala Riitta , Martikainen Rami , Estlander Tuula , Susitaival Päivikki , Aalto‐Korte Kristiina
Published: June 2005

Studies on the prevalence of hand dermatitis in construction painting are rare. Our aim was to study the painters' chemical exposure and the prevalence of self‐reported skin symptoms on hands and forearms. A cross‐sectional questionnaire survey was conducted on 1000 Finnish male construction painters and 1000 carpenters (response rates 60.6% and 60.4%, respectively). We used 2 definitions for symptom‐based hand dermatitis (liberal ≥ 2 symptoms and strict criteria ≥ 3) and logistic regression analysis, adjusted with age and atopy. Painters reported more symptoms of hand dermatitis than carpenters (12‐month prevalence 22.5% and 14.2%, P < 0.05; strict criteria 13.3% and 6.4%, P < 0.05). A dose–response relationship was found for reporting symptoms and exposure to several solvent‐based (SB) and water‐based (WB) products. When exposure was combined into 1 variable, daily use of SB epoxy/urethane paints (OR 5.3, 95% CI 2.2–12.9; strict criteria 6.8, 2.3–19.9) and WB putties/plasters (1.9, 1.2–3.0; strict criteria 2.0, 1.1–3.9) were associated with hand dermatitis, whereas using only WB paints was not a risk factor. In conclusion, painters reported significantly more symptoms of hand dermatitis than carpenters. Putties/plasters emerged as a risk factor for dermatitis in construction painting.
Preservatives in registered chemical products
Authors: Flyvholm Mari‐Ann
Published: June 2005

Preservatives are common causes of contact allergy and contact dermatitis. Exposure to cosmetics, personal care products, consumer products and occupationally used products often involve contact with the same range of preservatives. The aim of this study is to provide an overview on the occurrence of preservatives in registered chemical products. The studied preservatives included substances from standard patch test series and other preservatives relevant for registered chemical products. Data obtained from the Danish Product Register Database (PROBAS) in January 2005 were compared to similar data from January 2002. Paints/lacquers, cleaning agents and printing inks were the most frequently registered product categories, and the studied preservatives were registered in most of the product categories included in the study. For most product categories the total number of registered products was stable during the study period. Butylated hydroxytoluene, benzoic acid, isothiazolinones, Bronopol and formaldehyde showed an increase from 2002 to 2005. Most of these changes occurred in the product category paints/lacquers, for which a doubling mainly due to a change in registration practice was observed. The frequent registration of isothiazolinones (MCI/MI and benzisothiazolinone) in paints/lacquers may be a possible explanation for the relative high and stable frequency of positive patch test reactions to MCI/MI.
Patch test reactions to cosmetic allergens in 1995–1997 and 2000–2002 in Finland – a multicentre study
Authors: Hasan T. , Rantanen T. , Alanko K. , Harvima R. J. , Jolanki R. , Kalimo K. , Lahti A. , Lammintausta K. , Lauerma A. I. , Laukkanen A. , Luukkaala T. , Riekki R. , Turjanmaa K. , Varjonen E. , Vuorela A.‐M.
Published: June 2005

Contact sensitivity to cosmetics is common, but the sensitizing chemicals vary between countries and study periods. The present survey aimed at revealing the recent trends in patch test sensitivity with cosmetic chemicals in Finland. We report a retrospective multicentre survey of patch test reactions focusing on cosmetic‐related substances and comparing the test results in 1995–97 with those in 2000–02. The most striking increases in the frequency of the patch test sensitivity were found with balsam of Peru and propolis from 4.0% to 6.2% (P < 0.001) and from 0.5% to 1.4% (P < 0.001), respectively, whereas the most prominent decreases were found with methylchloro/methylisothiazolinone and chlorhexidine diglugonate from 2.4% to 1.3% (P < 0.001) and from 1.2% to 0.5% (P < 0.001), respectively. The level of patch test sensitivity to methyldibromo glutaronitrile increased, although not significantly, from 1.0% to 1.5%. An increasing tendency was also found with hair dye chemicals 4‐aminophenol and toluene‐2,5‐diamine or toluene‐2,5‐diamine sulfate from 1.3% to 3.8% and from 1.4% to 5.2%, respectively, while such a tendency was not found among permanent wave chemicals. The sensitivity level of fragrance mix remained the same (6% − 7%). We conclude that surveys revealing the state of sensitivity to cosmetic chemicals should be performed periodically in different countries.
The role of PFA‐100® testing in the investigation and management of haemostatic defects in children and adults
Authors: Harrison Paul
Published: June 2005

The PFA‐100® provides a simple global measure of high shear‐dependent platelet function, and as such is not diagnostic or specific to any disorder. Prolonged closure times must be interpreted in conjunction with a full blood count, von Willebrand factor (VWF) screen and other platelet tests. The PFA‐100® may also give false negative results with relatively common platelet defects. If clinical suspicion is high, further detailed platelet function testing and VWF screening are required to exclude abnormal platelet function, even if the PFA‐100® is normal. In more recent studies the PFA‐100® has been used for preoperative identification and management of surgical patients with haemostatic defects and for assessing the clinical effectiveness of platelet transfusion therapy. This review highlights the up to date, evidence‐based, advantages and disadvantages of the PFA‐100® test in the investigation and management of haemostatic disorders in both children and adults.
Can long‐term prophylaxis for severe haemophilia be stopped in adulthood? Results from Denmark and the Netherlands
Authors: van Dijk K. , Fischer K. , van der Bom J. G. , Scheibel E. , Ingerslev J. , van den Berg H. M.
Published: June 2005

Prophylaxis is the treatment of choice for children with severe haemophilia. As prophylaxis is especially important during the period of growth, the need for continued prophylaxis in adulthood should be considered. The aim of this study was to describe the incidence and outcome of stopping prophylaxis in patients with severe haemophilia who were offered prophylaxis during childhood. All patients with severe haemophilia (factor VIII/IX <0·01 IU/ml), born 1970–80, treated in two Danish and one Dutch treatment centre were studied. Data on discontinuation of prophylaxis, treatment, joint bleed frequency, clinical scores and radiological scores were collected. Eighty patients were studied. Median follow‐up was 19 years (range 7–29). A total of 35% of patients discontinued prophylaxis at a median age of 21·5 years [interquartile range (IQR) 18·4–24·4], experiencing only three joint bleeds per year (IQR 1·4–8·7). Median clinical scores were similar in patients who discontinued prophylaxis [4 points (IQR 0–6)] and those who continued [3 points (IQR 1–6)], as were median Pettersson scores at 13 (IQR 1–24) vs. 13 points (IQR 5–23) respectively. In conclusion one‐third of young adults with severe haemophilia on a prophylactic regimen discontinued prophylaxis in early adulthood, while maintaining a low joint bleed frequency and similar arthropathy after 4 years.
A novel human CD32 mAb blocks experimental immune haemolytic anaemia in FcγRIIA transgenic mice
Authors: van Royen‐Kerkhof Annet , Sanders Elisabeth A. M. , Walraven Vanessa , Voorhorst‐Ogink Marleen , Saeland Eirikur , Teeling Jessica L. , Gerritsen Arnout , van Dijk Marc A. , Kuis Wietse , Rijkers Ger T. , Vitale Laura , Keler Tibor , McKenzie Steven E. , Leusen Jeanette H. W. , van de Winkel Jan G. J.
Published: June 2005

A fully human IgG1 kappa antibody (MDE‐8) was generated, which recognised Fc‐gamma receptor IIa (FcγRIIa) molecules on CD32 transfectants, peripheral blood monocytes, polymorphonuclear cells and platelets. This antibody blocked FcγRIIa ligand‐binding via its F(ab′)2 fragment. Overnight incubation of monocytes with F(ab′)2 fragments of MDE‐8 leads to a c. 60% decrease in cell surface expression of FcγRIIa. MDE‐8 whole antibody induced a concomitant c. 30% decrease of FcγRI on THP‐1 cells and monocytes. In humans FcγRIIa plays an important role in the clearance of antibody‐coated red blood cells in vivo. As an equivalent of FcγRIIa does not exist in mice, the in vivo effect of MDE‐8 was studied in an FcγRIIa transgenic mouse model. In these mice, antibody‐induced anaemia could readily be blocked by MDE‐8. These data document a new human antibody that effectively blocks FcγRIIa, induces modulation of both FcγRIIa and FcγRI from phagocytic cells, and ameliorates antibody‐induced anaemia in vivo.
Autocrine/paracrine involvement of insulin‐like growth factor‐I and its receptor in chronic lymphocytic leukaemia
Authors: Schillaci Roxana , Galeano Adriana , Becu‐Villalobos Damasia , Spinelli Olga , Sapia Sandra , Bezares Raimundo F.
Published: June 2005

Chronic lymphocytic leukaemia (CLL) is characterized by the accumulation of long‐lived B lymphocytes blocked in G0/1 by impaired apoptosis. As insulin‐like growth factor‐I (IGF‐I) is known for its antiapoptotic effects in different cell types, we investigated whether IGF‐I and its receptor (IGF‐IR) participate in autocrine/paracrine loops affecting the survival of CLL cells. IGF‐IR protein and mRNA was present in CLL cells in 44% and 59% of patients respectively. IGF‐IR expression in CLL patients was positively correlated with the expression of the antiapoptotic protein Bcl‐2 and was involved in CLL cell survival in vitro. Serum IGF‐I was elevated in CLL patients, but growth hormone (GH) was normal. CLL cells expressed IGF‐I mRNA and secreted the growth factor in vitro. Therefore, local production of IGF‐I can account for the increased levels of serum IGF‐I, independently of GH, and may be related to autocrine/paracrine control of lymphocyte survival acting at IGF‐IR. This is the first demonstration of IGF‐IR expression in a subgroup of CLL patients and of its antiapoptotic effects in vitro, highlighting the importance of this growth factor receptor as a possible therapeutic target in CLL.
Downregulation of the major histocompatibility complex class I molecules by human herpesvirus type 8 and impaired natural killer cell activity in primary effusion lymphoma development
Authors: Sirianni Maria Caterina , Libi Fabio , Campagna Massimo , Rossi Davide , Capello Daniela , Sciaranghella Gaia , Carbone Antonino , Simonelli Cecilia , Monini Paolo , Gaidano Gianluca , Ensoli Barbara
Published: June 2005

Primary effusion lymphomas (PELs) are invariably infected by human herpesvirus type 8 (HHV8) and often co‐infected by Epstein–Barr virus (EBV). We found that expression of major histocompatibility complex class I (MHC‐I) surface molecules was significantly decreased in PEL cells when compared with HHV8 negative lymphomas, irrespective of EBV infection. MHC‐I downregulation rendered PEL cells sensitive to recognition and killing by natural killer (NK) cells. Intriguingly, analysis of MHC‐I non‐restricted cytotoxicity in two PEL patients indicated a reduced NK cell activity when compared with healthy individuals. These data suggest that PEL outgrowth may require an impaired NK cell function.
The Differential Effects of Biofeedback in the Treatment of Classical and Common Migraine
Authors: Gauthier Janel , Fradet Christiane , Roberge Claude
Published: June 2005

SYNOPSIS

The aim of the present study was to test the hypothesis that patients whose headaches are usuallypreceded by prodromes would derive more benefits from biofeedback than those who do not have anywarnings. Accordingly, 39 female patients were assigned to either of two conditions: classical migraine(n=17) or common migraine (n=22) depending on the characteristics of their headaches. The classicalmigraine condition included only patients whose headaches were usually or always associated with visualprodromes while the common migraine condition included patients whose headache were never or rarelyassociated with any kind of prodromes. All patients completed 5 weeks of daily self‐monitoring ofheadache activity and medication intake before and after treatment, and at 6‐month follow‐up. Resultsshowed that patients in the classical migraine condition improved significantly more than those in thecommon migraine group. Various explanations for the differential effects of biofeedback in the treatment ofclassical and common migraine are discussed and suggestions for further research are made.
The Pain Behavior Questionnaire (PBQ): A Global Report of Pain Behavior inChronic Headache
Authors: Appelbaum Kenneth A. , Radnitz Cynthia L. , Blanchard Edward B. , Prins Annabel
Published: June 2005

SYNOPSIS

The Pain Behavior Questionnaire (PBQ), adapted from an earlier version by Philips and Hunter,1 wasadministered to 165 chronic headache patients (migraine, tension, and mixed migraine and tension) duringa pre‐treatment assessment, and asked for a retrospective report of the frequency of engaging in variouspain‐related behaviors during periods of headache. An exploratory factor analysis identified four factors:avoidance (Factor 1), complaint (Factor 2), non‐verbal complaint (Factor 3), and medication consumption(Factor 4). Additionally, the relationship between behavioral factors and a prospective index of headacheactivity was calculated. In all cases, for the entire sample, and for each diagnostic group, the correlationswere negative, indicating some lack of congruence between a measure of pain and pain behaviors. Finally,the relationship between indices of psychopathology and pain behaviors was assessed utilizing the BeckDepression Inventory (BDI), and the Trait portion of the State‐Trait Anxiety Inventory (STAI). Scores on theBDI were significantly positively correlated with Factors 1, 3 and 4. Scores on the STAI were significantlypositively correlated with all four of the behavioral factors. These results indicate that the pain experiencemay be mediated by factors other than the subjective experience of pain itself.