bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of signalling efficacy by palmitoylation of the rat Y1 receptor
Authors: Holliday Nicholas D , Cox Helen M
Published: June 2003

We have investigated the properties of native and haemagglutinin (HA)‐tagged neuropeptide Y (NPY) Y1 receptors after mutation of the palmitoylation site Cys337 to Ser or Ala.

In Chinese hamster ovary cells expressing similar receptor levels, the C337A mutation abolished incorporation of [3H]palmitic acid into the HA‐Y1 receptor.

Cys337 substitution did not alter the affinities of Y1 receptor agonists or antagonists, but it eliminated the ability of guanosine‐5′‐O‐(3‐thio)triphosphate (GTPγS) to displace [125I]PYY‐specific binding (compared to approximately 50% inhibition in Y1 or HA‐Y1 clones).

Stimulation of GTPγ[35S] binding by native and HA‐Y1 receptors in standard incubation buffer (100 mM NaCl, 10 μM GDP) was prevented by Cys337 mutation. In this assay, the function of Y1(C337S) receptors could be partially rescued by reducing the Na+ concentration, and when overexpressed (Bmax: ∼10 pmol mg−1), both HA‐Y1 and HA‐Y1(C337A) receptors displayed similar responses to NPY and peptide YY (PYY).

In stably transfected adenocarcinoma cells expressing Y1 or Y1(C337S) receptors, PYY inhibited anion secretion stimulated by vasoactive intestinal peptide (VIP; measured as short‐circuit current, ISC) with similar potency (EC50: 26–53 nM). In contrast to the transient Y1 receptor‐mediated responses observed at maximal PYY concentrations, ISC reductions in both Y1(C337S) clones were sustained.

We conclude that nonpalmitoylation of the Y1 receptor reduces its coupling efficiency to G proteins, and may also indirectly influence desensitisation processes that depend on the formation of an active agonist‐receptor conformation.

British Journal of Pharmacology (2003) 139, 501–512. doi:10.1038/sj.bjp.0705276
Effect of sildenafil on cyclic nucleotide phosphodiesterase activity, vascular tone and calcium signaling in rat pulmonary artery
Authors: Pauvert O , Lugnier C , Keravis T , Marthan R , Rousseau E , Savineau J P
Published: June 2003

Sildenafil (viagra) is a potent PDE5 inhibitor and thus a relaxant drug in corpus carvernosum smooth muscle. In the present work, we evidenced the presence of PDE5 isozyme and investigated the effect of sildenafil on the specific cyclic nucleotide phosphodiesterase (PDE) activity, smooth muscle tone and calcium signaling in the rat main pulmonary artery (MPA).

The PDE activity was measured in cytosolic and microsomal fractions. Total cAMP and cGMP‐PDE activities were mainly present in the cytosolic fraction. Sildenafil (0.1 μM) reduced by 72% cGMP‐PDE activity, whereas zaprinast (10 μM), a relatively selective PDE5 inhibitor, reduced this activity by 63%. Sildenafil (0.1 μM) also inhibited significantly (22%) the cAMP‐PDE activity.

Western blot analysis revealed the expression of PDE5 mainly in the cytosolic fraction of MPA. Sildenafil concentration‐dependently inhibited (IC50=3.4 nM) the activity of MPA PDE5 partially purified by HPLC.

Sildenafil (0.1 nM–50 μM) concentration‐dependently relaxed MPA rings precontracted with phenylephrine (0.5 μM). The potency of sildenafil (IC50=11 nM) was similar to that of a nitric oxide donor, sodium nitroprusside, but higher than that of zaprinast (IC50=600 nM). The vasorelaxant effect of sildenafil was not altered by endothelium removal or in the presence of KT 5823 (1 μM) and H89 (1 μM), potent inhibitors of PKG and PKA, respectively.

In isolated MPA myocytes, which had been loaded with the calcium fluorophore indo‐1, sildenafil (10–100 nM) antagonized ATP‐ and endothelin‐1‐induced calcium oscillations but had no effect on the transient caffeine‐induced [Ca2+]i response.

This study demonstrates the presence of a functional and highly sildenafil‐sensitive PDE5 isozyme in rat MPA. Inhibition of this isozyme mainly accounts for the potent pulmonary vasodilator action of sildenafil, which involves alteration in the inositol triphosphate‐mediated calcium signaling pathway.

British Journal of Pharmacology (2003) 139, 513–522. doi:10.1038/sj.bjp.0705277
Tachykinins and tachykinin receptors in human uterus
Authors: Patak Eva , Luz Candenas M , Pennefather Jocelyn N , Ziccone Sebastian , Lilley Alison , Martín Julio D , Flores Carlos , Mantecón Antonio G , Story Margot E , Pinto Francisco M
Published: June 2003

Studies were undertaken to determine the nature of the receptors mediating contractile effects of tachykinins in the uteri of nonpregnant women, and to analyse the expression of preprotachykinins (PPT), tachykinin receptors and the cell‐surface peptidase, neprilysin (NEP), in the myometrium from pregnant and nonpregnant women.

The neurokinin B (NKB) precursor PPT‐B was expressed in higher levels in the myometrium from nonpregnant than from pregnant women. Faint expression of PPT‐A mRNA was detectable in the myometrium from nonpregnant but not pregnant women. PPT‐C, the gene encoding the novel tachykinin peptide hemokinin‐1 (HK‐1), was present in trace amounts in the uteri from both pregnant and nonpregnant women.

Tachykinin NK2 receptors were more strongly expressed in tissues from nonpregnant than from pregnant women. NK1 receptor mRNA was present in low levels in tissues from both pregnant and nonpregnant women. A low abundance transcript corresponding to the NK3 receptor was present only in tissues from nonpregnant women.

The mRNA expression of the tachykinin‐degrading enzyme NEP was lower in tissues from nonpregnant than from pregnant women.

Substance P (SP), neurokinin A (NKA) and NKB, in the presence of the peptidase inhibitors thiorphan, captopril and bestatin, produced contractions of myometrium from nonpregnant women. The order of potency was NKA≫SP≥NKB. The potency of NKA was unchanged in the absence of peptidase inhibitors.

The tachykinin NK2 receptor‐selective agonist [Lys5MeLeu9Nle10]NKA(4–l0) was approximately equipotent with NKA, but the tachykinin NK1 and NK3 receptor‐selective agonists [Sar9Met(O2)11]SP and [MePhe7]NKB were ineffective in the myometrium from nonpregnant women.

The uterotonic effects of [Lys5MeLeu9Nle10]NKA(4–10) were antagonized by the tachykinin NK2 receptor‐selective antagonist SR48968. Neither atropine, nor phentolamine nor tetrodotoxin affected responses to [Lys5MeLeu9Nle10]NKA(4–10).

These data are consistent with a role of tachykinins in the regulation of human uterine function, and reinforce the importance of NK2 receptors in the regulation of myometrial contraction.

British Journal of Pharmacology (2003) 139, 523–532. doi:10.1038/sj.bjp.0705279
Dihydropyridine Ca2+ channel antagonists and agonists block Kv4.2, Kv4.3 and Kv1.4 K+ channels expressed in HEK293 cells
Authors: Hatano Noriyuki , Ohya Susumu , Muraki Katsuhiko , Giles Wayne , Imaizumi Yuji
Published: June 2003

We have determined the molecular basis of nicardipine‐induced block of cardiac transient outward K+ currents (Ito). Inhibition of Ito was studied using cloned voltage‐dependent K+ channels (Kv) channels, rat Kv4.3L, Kv4.2, and Kv1.4, expressed in human embryonic kindey cell line 293 (HEK293) cells.

Application of the dihydropyridine Ca2+ channel antagonist, nicardipine, accelerated the inactivation rate and reduced the peak amplitude of Kv4.3L currents in a concentration‐dependent manner (IC50: 0.42 μM). The dihydropyridine (DHP) Ca2+ channel agonist, Bay K 8644, also blocked this K+ current (IC50: 1.74 μM).

Nicardipine (1 μM) slightly, but significantly, shifted the voltage dependence of activation and steady‐state inactivation to more negative potentials, and also slowed markedly the recovery from inactivation of Kv4.3L currents.

Coexpression of K+ channel‐interacting protein 2 (KChIP2) significantly slowed the inactivation of Kv4.3L currents as expected. However, the features of DHP‐induced block of K+ current were not substantially altered.

Nicardipine exhibited similar block of Kv1.4 and Kv4.2 channels stably expressed in HEK293 cells; IC50's were 0.80 and 0.62 μM, respectively.

Thus, at submicromolar concentrations, DHP Ca2+ antagonist and agonist inhibit Kv4.3L and have similar inhibiting effects on other components of cardiac Ito, Kv4.2 and Kv1.4.

British Journal of Pharmacology (2003) 139, 533–544. doi:10.1038/sj.bjp.0705281
Molecular cloning and characterization of avian bombesin‐like peptide receptors: new tools for investigating molecular basis for ligand selectivity
Authors: Iwabuchi Maiko , Ui‐Tei Kumiko , Yamada Kazuhiko , Matsuda Yoichi , Sakai Yasushi , Tanaka Kohichi , Ohki‐Hamazaki Hiroko
Published: June 2003

Bombesin (BN), originally isolated from amphibians, is structurally related to a family of BN‐like peptides found in mammals, which include gastrin‐releasing peptide (GRP) and neuromedin B (NMB). These peptides have important effects on secretion, smooth muscle contraction, metabolism and behavior. Here we report cloning and characterization of two subtypes of BN‐like peptide receptors in Aves.

The amino‐acid sequence of chick GRP‐R (chGRP‐R) is highly identical with mammalian and amphibian GRP‐R, and this receptor showed high affinity for GRP, BN and synthetic bombesin agonist, [D‐Phe6, β‐Ala11, Phe13, Nle14]bombesin(6–14) ([FAFNl]BN(6–14)). The chGRP‐R gene was localized to chicken chromosome 1q23distal‐q24proximal, where chick homologs of other human X‐linked genes have also been mapped.

ChBRS‐3.5, having sequence similarities to both mammalian bombesin‐like peptide receptor subtype‐3 and amphibian bombesin‐like peptide receptor subtype‐4, showed high affinity for [FAFNl]BN(6–14), moderate affinity for BN, but low affinity for both GRP and NMB.

Expression of both receptors was detected in brain, but only chGRP‐R was expressed in gastrointestinal (GI) tissues.

When expressed in Chinese hamster ovary K1 cells, these receptors mediate intracellular calcium mobilization upon agonist stimulation. These results suggest that a novel BN peptide may occur in Aves as an endogenous ligand for chBRS‐3.5.

The receptor sequences responsible for ligand selectivities were discussed and this knowledge about avian BN‐like peptide receptors will help us to understand the molecular basis for agonist sensitivities of BN‐like peptide receptors.

British Journal of Pharmacology (2003) 139, 555–566. doi:10.1038/sj.bjp.0705282
The antipsychotic drug chlorpromazine inhibits HERG potassium channels
Authors: Thomas Dierk , Wu Kezhong , Kathöfer Sven , Katus Hugo A , Schoels Wolfgang , Kiehn Johann , Karle Christoph A
Published: June 2003

Acquired long QT syndrome (aLQTS) is caused by prolongation of the cardiac action potential because of blockade of cardiac ion channels and delayed repolarization of the heart. Patients with aLQTS carry an increased risk for torsade de pointes arrhythmias and sudden cardiac death. Several antipsychotic drugs may cause aLQTS. Recently, cases of QTc prolongation and torsade de pointes associated with chlorpromazine treatment have been reported. Blockade of human ether‐a‐go‐go‐related gene (HERG) potassium channels, which plays a central role in arrhythmogenesis, has previously been reported to occur with chlorpromazine, but information on the mechanism of block is currently not available. We investigated the effects of chlorpromazine on cloned HERG potassium channels to determine the biophysical mechanism of block.

HERG channels were heterologously expressed in Xenopus laevis oocytes, and ion currents were measured using the two‐microelectrode voltage‐clamp technique.

Chlorpromazine blocked HERG potassium channels with an IC50 value of 21.6 μM and a Hill coefficient of 1.11.

Analysis of the voltage dependence of block revealed a reduction of inhibition at positive membrane potentials.

Inhibition of HERG channels by chlorpromazine displayed reverse frequency dependence, that is, the amount of block was lower at higher stimulation rates. No marked changes in electrophysiological parameters such as voltage dependence of activation or inactivation, or changes of the inactivation time constant were observed.

In conclusion, HERG channels were blocked in the closed and activated states, and unblocking occurred very slowly.

British Journal of Pharmacology (2003) 139, 567–574. doi:10.1038/sj.bjp.0705283
Homo‐ and heteroexchange of adenine nucleotides and nucleosides in rat hippocampal slices by the nucleoside transport system
Authors: Sperlágh Beáta , Szabó Gábor , Erdélyi Ferenc , Baranyi Mária , Sylvester Vizi E
Published: June 2003

Here, we investigated how nucleotides and nucleosides affect the release of tritiated purines and endogenous adenosine 5′‐triphosphate (ATP) from superfused rat hippocampal slices.

ATP elicited concentration‐dependent [3H]purine efflux from slices preloaded with [3H]adenosine. High‐performance liquid chromatography analysis of the effluent showed that the tritium label represented the whole set of adenine nucleotides and nucleosides, and ATP significantly increased the outflow of [3H]ATP.

Adenosine 5′‐diphosphate, adenosine, uridine, uridine 5′‐triphosphate, α,β‐methylene‐ATP and 3′‐O‐(4‐benzoylbenzoyl)‐ATP were also active in eliciting [3H]purine release. Adenosine (300 μM) also evoked endogenous ATP efflux from the hippocampal slices.

Reverse transcription‐coupled‐polymerase chain reaction analysis revealed that mRNAs encoding a variety of P2X and P2Y receptor proteins are expressed in the rat hippocampus. Nevertheless, neither P2 receptor (i.e. pyridoxal‐5‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid, 30 μM, suramin, 300 μM and reactive blue 2, 10 μM), nor adenosine receptor (8‐cyclopentyl‐1,3‐dipropylxanthine, 250 nM and dimethyl‐1‐propargylxanthine, 250 nM) antagonists modified the effect of ATP (300 μM) to evoke [3H]purine release.

The nucleoside transport inhibitors, dipyridamole (10 μM), nitrobenzylthioinosine (10 μM) and adenosine deaminase (2–10 U ml−1), but not the ecto‐adenylate kinase inhibitor diadenosine pentaphosphate (200 μM) significantly reduced ATP‐evoked [3H]purine efflux.

In summary, we found that ATP and other nucleotides and nucleosides promote the release of one another and themselves by the nucleoside transport system. This action could have relevance during physiological and pathological elevation of extracellular purine levels high enough to reverse the nucleoside transporter.

British Journal of Pharmacology (2003) 139, 623–633. doi:10.1038/sj.bjp.0705285
A ‘benign addition’? Research on ICT and pre‐school children
Authors: Plowman L. , Stephen C.
Published: June 2003

Abstract This paper reviews the international research evidence on the ways in which information and communication technologies (ICT) are used in both formal and informal pre‐school settings. The review addresses the debate over the value and desirability of young children using computers and computational toys; the relationship of these technologies to a media environment which encompasses television, video, books and magazines; the literacies involved in using these media; and interface design and interactivity.
Children's interactions with interactive toy technology
Authors: Luckin R. , Connolly D. , Plowman L. , Airey S.
Published: June 2003

Abstract Digital toys offer the opportunity to explore software scaffolding through tangible interfaces that are not bound to the desktop computer. This paper describes the empirical work completed by the CACHET (Computers and Children's Electronic Toys) project team investigating young children's use of interactive toy technology. The interactive toys in question are plush and cuddly cartoon characters with embedded sensors that can be squeezed to evoke spoken feedback from the toy. In addition to playing with the toy as it stands, the toy can be linked to a desktop PC with compatible software using a wireless radio connection. Once this connection is made the toy offers hints and tips to the children as they play with the accompanying software games. If the toy is absent, the same hints and tips are available through an on‐screen animated icon of the toy's cartoon character. The toys as they stand are not impressive as collaborative learning partners, as their help repertoire is inadequate and even inappropriate. However, the technology has potential: children can master the multiple interfaces of toy and screen and, when the task requires it and the help provided is appropriate, they will both seek and use it. In particular, the cuddly interface experience can offer an advantage and the potential for fun interfaces that might address both the affective and the effective dimensions of learners' interactions.
Virtual peers as partners in storytelling and literacy learning
Authors: Ryokai K. , Vaucelle C. , Cassell J.
Published: June 2003

Abstract Literacy learning — learning how to read and write — begins long before children enter school. One of the key skills to reading and writing is the ability to represent thoughts symbolically and share them in language with an audience who may not necessarily share the same temporal and spatial context. Children learn and practice these important language skills everyday, telling stories with the peers and adults around them. In particular, storytelling in the context of peer collaboration provides a key environment for children to learn language skills important for literacy. In light of this, an embodied conversational agent,Sam, who tells stories collaboratively with children was designed.Samlooks like a peer for pre‐school children, but tells stories in a developmentally advanced way, modelling narrative skills important for literacy. Results demonstrated that children who played with the virtual peer told stories that more closely resembled the virtual peer's linguistically advanced stories: using more quoted speech and temporal and spatial expressions. In addition, children listened toSam'sstories carefully, assisting her and suggesting improvements. The potential benefits of having technology play a social role in young children's literacy learning is discussed.
The effects of multiple mice on children's talk and interaction
Authors: Stanton D. , Neale H.R.
Published: June 2003

Abstract A classroom‐based evaluation study examined the process of children's collaboration when using one or two mice at a desktop computer. Pairs of children worked together to re‐create a poem in pictorial format. In‐depth qualitative examination of interaction using ‘collaboration networks’ highlighted differences in working styles between conditions. Children using two mice divided up their task, worked in parallel, and showed limited reciprocity and elaboration of ideas. Children sharing one mouse demonstrated varied behaviours ranging from highly collaboratively work to extreme domination by one partner. The implications of these results for the organisation of tasks are discussed.
Male mating success in relation to food availability in the common goby
Authors: Svensson O. , Forsgren E.
Published: June 2003

In a feeding experiment with the common goby Pomatoschistus microps, there was no female preference for well‐fed males, although these males had a higher mating success. This suggests that care should be taken about drawing conclusions regarding mate choice and mating success based on mate preference tests alone.
Reproductive biology of Vinciguerria nimbaria in the equatorial waters of the eastern Atlantic Ocean
Authors: Stequert B. , Menard F. , Marchal E.
Published: June 2003

Adult Vinciguerria nimbaria in an area of the Atlantic Ocean (0–5°N; 10–20°W), collected from November 1994 to February 1998, exhibited two different patterns in diel behaviour: ‘typical’ behaviour which consisted of large diel vertical migration and ‘atypical’, characterized by concentrations of schools that remained in the surface layers during the daytime. The total life span of V. nimbaria was estimated at 6–7 months. Females were mature when they reached 30·6 mm standard length (LS), which corresponded to an age of 85 days. Once the females were mature, spawning was continuous in the population as a whole, and V. nimbaria spawned continuously throughout the year. Spawning took place during two restricted times of the day: typical females spawned at dusk and atypical females spawned at dawn. Using the post‐ovulatory follicles method, spawning frequency was estimated at 2 days. Batch fecundity was estimated at 1236 oocytes or 1230 oocytes g−1 of total body mass, and egg size was 650 µm whatever the period of the year. The lifetime fecundity of V. nimbaria was estimated at 9000 eggs (109 000 eggs if mortality rate was not taken into account), and the maximum stock egg production of a theoretical cohort occurred at 37 mm LS. Young adults thus contributed the most to the reproductive output for the survival of the population.
Large‐scale genetic differentiation of Pagrus pagrus in the Atlantic
Authors: Ball A. O. , Sedberry G. R. , Wessel J. H. , Chapman R. W.
Published: June 2003

Red porgy Pagrus pagrus from the north‐eastern, north‐western and south‐western Atlantic were found to be genetically distinct as determined by mitochondrial DNA analysis. There were no shared composite restriction fragment haplotypes, and nucleotide sequence differences averaged 2% among these locations.
Variability in determination of point of needle insertion in peripheral nerve blocks: A comparison of experienced and inexperienced anaesthetists
Authors: Grant S. A. , Breslin D. S. , MacLeod D. B. , Demeyts D. , Martin G. , D'Ercole F. , Hardman D.
Published: June 2003

Accurate identification of surface landmarks is essential for the successful performance of peripheral nerve blocks. The variability between experienced and inexperienced practitioners in identifying anatomical landmarks has not been studied previously. Anaesthetists were asked to identify the point of needle insertion for posterior lumbar plexus and sciatic nerve blocks on a volunteer using a standard textbook description. The chosen point for needle insertion was described in terms of X and Y co‐ordinates, measured in millimetres, from a zero reference point marked on a volunteer's back. Fifteen experienced and 22 inexperienced anaesthetists took part in the study. The lumbar plexus block mean [range] values for the X, Y co‐ordinates were 80 [62–108], 66 [46–86] and 92 [49–150], 62 [0–131] in the experienced and inexperienced groups, respectively. The sciatic nerve block X, Y co‐ordinates were 77 [62–99], 70 [49–89] and 68 [29–116], 62 [26–93] in the experienced and inexperienced groups, respectively. The variance for the point of needle insertion was significantly greater in the inexperienced group (p < 0.01) for both the lumbar plexus and sciatic nerve blocks. We conclude that with increasing experience, there is decreased variability in determining the point of needle insertion using anatomical landmarks.
A comparison of intra‐operative or postoperative exposure to music – a controlled trial of the effects on postoperative pain
Authors: Nilsson U. , Rawal N. , Unosson M.
Published: June 2003

The effect of intra‐operative compared to postoperative music on postoperative pain was evaluated in a controlled trial. In all, 151 patients undergoing day case surgery for inguinal hernia repair or varicose vein surgery under general anaesthesia were randomly allocated to three groups: group 1 listened to music intra‐operatively, group 2 listened to music postoperatively and group 3, the control group, listened to ‘white noise’. The anaesthetic and postoperative analgesic techniques were standardised. Pain was assessed using a numeric rating scale (0–10) and patients requirements for postoperative morphine, paracetamol and ibuprofen was recorded. The effect of music on nausea, fatigue and anxiety was also investigated. The results showed that patients exposed to music intra‐operatively or postoperatively reported significantly lower pain intensity at 1 and 2 h postoperatively and patients in the postoperative music group required less morphine at 1 h compared to the control group. No differences were noted in the other variables. This study demonstrates that there is a short‐term pain‐reducing effect of music therapy however, the beneficial effects do not differ if the patient is exposed to music intra‐operatively or postoperatively.
The information requested by patients prior to giving consent to anaesthesia
Authors: Moores A. , Pace N. A.
Published: June 2003

Patients in a teaching hospital in Scotland were given the opportunity to ask for further information relating to their peri‐operative anaesthetic management. One investigator visited all of the patients pre‐operatively and asked a standard list of anaesthetic‐related questions. Our objectives were to determine what additional information patients would request before giving their consent to anaesthesia. The majority of patients (n=469, 67%) had no further questions at a point when so‐called consent could have been obtained. Of the questions asked, 209 (66%) were related to anaesthesia and 93 (30%) to the proposed surgery. Only two patients in the group studied requested a full explanation of their peri‐operative anaesthetic management. The question most commonly asked related to the duration of surgery, with less priority being given to questions relating to complications of anaesthesia.
A comparison of cyclizine, ondansetron and placebo as prophylaxis against postoperative nausea and vomiting in children*
Authors: O'Brien C. M. , Titley G. , Whitehurst P.
Published: June 2003

Summary Nausea and vomiting is a relevant and common problem with unfavourable sequelae in children undergoing some plastic surgery procedures. There is a lack of anti‐emetic trials performed in children, with only a few investigating the roles of the older anti‐emetic agents such as cyclizine compared with newer ones such as ondansetron. This randomised, controlled, double‐blind study examined the effectiveness of a single dose of ondansetron (0.1 mg.kg−1), cyclizine (20 mg) and placebo (normal saline) in the prevention of postoperative nausea and vomiting in 150 children (mean age 3.6 years) undergoing plastic genitourinary procedures. Rates of previous postoperative nausea and vomiting and motion sickness were comparable across the groups. Postoperative vomiting was significantly reduced with ondansetron prophylaxis (p = 0.006) but there was no detectable anti‐emetic effect with cyclizine. Furthermore, cyclizine caused pain on injection (p < 0.001).
Effect of milrinone on vecuronium‐induced neuromuscular block
Authors: Nakajima H. , Hattori H. , Aoki K. , Katayama T. , Saitoh Y. , Murakawa M.
Published: June 2003

We examined the effect of milrinone, a phosphodiesterase III inhibitor, on neuromuscular block induced by vecuronium. Thirty adult patients were randomly assigned to one of two equal groups: the milrinone group and the control group. Subjects in the milrinone group received an intravenous loading dose of milrinone 5 μg.kg−1.min−1 for 10 min, followed by an infusion at a rate of 0.5 μg.kg−1.min−1. Subjects in the control group received normal saline at a rate of 0.1 ml.kg−1.h−1. Thirty minutes after the beginning of the infusion of milrinone, anaesthesia was induced with intravenous thiopental 4 mg.kg−1 and fentanyl 2 μg.kg−1, and was maintained with isoflurane in oxygen and nitrous oxide. Neuromuscular blockade was monitored electromyographically at the adductor pollicis muscle. The times from the administration of vecuronium 0.1 mg.kg−1 to the onset of neuromuscular block and the return of the first, second, third, and fourth response of the train‐of‐four were compared between the two groups. Times to the recovery of the ratio of the first twitch to the control twitch to 25%, 50% and 75%, and times to the recovery of train‐of‐four ratio to 25%, 50% and 75% were also compared between the two groups. The onset of neuromuscular block in the milrinone group was significantly slower than in the control group. The times to the returns of the four twitches of the train‐of‐four, times to recovery of the ratio of the first twitch to the control twitch to 25% and 50%, and the times to the recovery of the train‐of‐four ratio to 25% and 50% were significantly shorter in the milrinone group than in the control group. We conclude that milrinone delays the onset of neuromuscular blockade but hastens its recovery in anaesthetised patients receiving vecuronium.
Evaluation of personal, environmental and biological exposure of paediatric anaesthetists to nitrous oxide and sevoflurane*
Authors: Raj N. , Henderson K. A. , Hall J. E. , Aguilera I. M. , Harmer M. , Hutchings A. , Williams B.
Published: June 2003

Summary Paediatric anaesthetists are at higher risk of exposure to waste anaesthetic gases, which often exceed set safety limits. Recommended personal diffusive sampling techniques for monitoring exposure to waste anaesthetic gases may not give a true profile of exposure and hence biological sampling may also be necessary. We evaluated the exposure of paediatric anaesthetists to nitrous oxide and sevoflurane as assessed by personal environmental and biological samples. The influence of venue and technique, and the strength of the relationship among the various sampling techniques were analysed. The study found that exposure to nitrous oxide during paediatric anaesthetic inductions is still a major problem, although exposure to sevoflurane was usually within the accepted limits. The type of breathing system used and the presence of scavenging seem to influence this exposure, though surprisingly, the induction technique or the methods of airway control do not. No significant relationship was found between the various biological indicators measured.
Influence of glucose control, lipoproteins, and haemostasis function on brachial endothelial reactivity and carotid intima‐media area, stiffness and diameter in Type 1 diabetes mellitus patients
Authors: Johansson J. , Reichard P. , Jensen‐Urstad K. , Rosfors Stefan , Jensen‐Urstad M.
Published: June 2003

BackgroundThe objectives of this study were to determine the influence of glucose control on lipoprotein and haemostasis variables in Type 1 diabetes mellitus patients and to evaluate the global impact of these metabolic risk factors on brachial artery reactivity and carotid artery atherosclerosis, stiffness and diameter.

DesignFollow up of Type 1 diabetes patients randomized to insulin‐intensive conventional treatment (ICT,n = 29) or insulin‐standard treatment (ST,n = 25) in the Stockholm Diabetes Intervention Study (SDIS) more than 14 years ago.

ResultsThe intensive conventional treatment patients had lower glycosylated haemoglobin (HbA1c) compared with the ST patients, i.e. 7·01 (SD 0·51) vs. 8·31 (0·97), while concentrations of the lipoprotein and haemostasis variables analyzed were virtually similar. The carotid artery intima‐media area was associated with high HbA1c, high serum (S)‐cholesterol levels, and low high‐density lipoprotein (HDL)‐cholesterol levels. Carotid artery stiffness was associated with high systolic blood pressure, high HbA1c, high fibrinogen, and high HDL‐cholesterol. Brachial artery endothelial reactivity was higher for women and those with low S‐cholesterol.

ConclusionIn patients with Type 1 diabetes, glucose control appeared to have no effect on either lipoproteins or haemostasis variable concentrations. Poor glucose control, and high levels of S‐cholesterol, systolic blood pressure and plasma fibrinogen were associated with development of atherosclerosis, thus emphasising the importance of global risk factor control in patients with Type 1 diabetes mellitus.
Exercise induces excessive normetanephrine responses in hypertensive diabetic patients
Authors: Raber W. , Raffesberg W. , Waldhäusl W. , Gasic S. , Roden M.
Published: June 2003

Background Exaggerated sympathoadrenal function has been accused of contributing to hypertension in type‐2 diabetes. Recently, plasma unconjugated (free) metanephrines were reported to be stable markers of catecholamine hypersecretion. Thus, we aimed to examine whether unconjugated metanephrines are reliable markers of stress response induced by standardized cycling exercise and to identify differences in such stress responses between hypertensive and/or diabetic patients.

Design Type‐2 diabetic patients with (DM/H; n= 8, 50 ± 7 years, HbA1c: 7·7 ± 0·6%) or without hypertension (DM/N; n = 6, 48 ± 10 years, 7·5 ± 1·8%) and nondiabetic hypertensive patients (H; n = 8, 56 ± 4 years) were studied during incremental cycling exercise (15 min) to 75% of individual VO2max and during recovery (60 min). Plasma catecholamines and unconjugated metanephrines were measured by high‐performance liquid chromatography with electrochemical detection. Hormone responses were quantified from the areas under the concentration‐time curves and compared with those of age‐, sex‐ and BMI‐matched healthy volunteers (CON, n= 22).

Results Blood pressure responses of DM/H and H, but not DM/N, were greater than those of CON (P < 0·01), whereas heart rates increased similarly in all groups. Unconjugated normetanephrine responses were only increased (P = 0·04) in DM/H (2156 vs. 1133 pg mL−1 min−1) but not in DM/N (1528 vs. 1300 pg mL−1 min−1) and H (1960 vs. 1425 pg mL−1 min−1) when compared with respective CON. Unconjugated metanephrines did not change from baseline, whereas catecholamine responses were comparable in all groups.

Conclusions The excessive response of plasma unconjugated normetanephrine to cycling may serve as a marker of exaggerated sympathoadrenal function in hypertensive type‐2 diabetic patients.
Heat‐shock protein 70 favours human liver recovery from ischaemia‐reperfusion
Authors: Boeri D. , Dondero F. , Storace D. , Maiello M. , Pasqualini M. , Pellicci R.
Published: June 2003

Background Pringle's manoeuvre controls excessive bleeding, but results in ischaemia‐reperfusion injury during liver surgery. Activation of the heat‐shock protein system of cell defense has been demonstrated after ischaemia‐reperfusion injury in animal tissues. The aim of the present study was to determine whether the ischaemia‐reperfusion accompanying hepatic surgery induces heat‐shock protein 70 (HSP70) in human liver and whether the induction of HSP70 is related to the recovery of liver function.

Methods Heat‐shock protein 70 and γ‐actin mRNAs were assayed in the liver biopsies of 10 subjects undergoing partial hepatectomy for localized lesions. Measurements were performed before the Pringle's manoeuvre and at the end of the surgery. Transaminases and fibrinogen were measured before and at 12, 24 and 36 h following hepatectomy.

Results After an average 40 ± 8‐min period of warm ischaemia, a significant increase of HSP70 mRNA (187 ± 67%, 2P < 0·05) was observed. The acute increase of HSP70 mRNA correlates with the decrease of transaminases (AST: rs −0·964, ALT: rs –0·891, P < 0·002) and the increase of fibrinogen (rs −0·7, P < 0·02) observed between 12 and 24 h following surgery.

Conclusions Heat‐shock protein 70 is induced by ischaemia‐reperfusion injury in human liver. Its induction seems to have beneficial effects, including a prompt reduction of transaminases and a rapid recovery of fibrinogen synthesis.
Low HDL cholesterol concentration is associated with increased intima‐media thickness independent of arterial stiffness in healthy subjects from families with low HDL cholesterol
Authors: Alagona C. , Soro A. , Westerbacka J. , Ylitalo K. , Salonen J.T. , Salonen R. , Yki‐Järvinen H. , Taskinen M.‐R.
Published: June 2003

Background Low high‐density lipoprotein cholesterol (HDL‐C) is associated with increased risk for developing coronary artery disease. Cardiovascular disease is characterized by increased intima‐media thickness (IMT) and arterial stiffness, but the effect of low HDL on these measurements has not been reported.

Materials and methods We studied 18 apparently healthy subjects from families with low HDL‐C and 18 control subjects, which were pair‐matched to maximize statistical power. Intima‐media thickness was assessed using ultrasound examination of the carotid arteries. Arterial stiffness was measured using applanation tonometry on the radial artery and pulse‐wave analysis to obtain central aortic pulse‐pressure waveform, from which the augmentation index, a measure of global large artery stiffness, was calculated.

Results Low HDL subjects (age 41 ± 3 years, BMI 26·6 ± 1·0 kg m−2) had significantly lower HDL‐C than the control subjects (age 41 ± 3 years, BMI 26·5 ± 1·0 kg m−2; 1·00 ± 0·05 vs. 1·49 ± 0·09 mmol L−1, low HDL vs. control subjects, P < 0·0001). Subjects with low HDL‐C had significantly thicker mean IMTs than the control subjects (0·77 ± 0·03 vs. 0·70 ± 0·02 mm, low HDL vs. control subjects, P < 0·01). The maximal (0·99 ± 0·04 vs. 0·89 ± 0·03 mm, P < 0·01), far wall (0·76 ± 0·04 vs. 0·69 ± 0·02 mm, P < 0·05) and carotid bulb (1·11 ± 0·06 vs. 0·97 ± 0·04 mm) IMTs were also significantly increased, whereas the mean common carotid and the internal artery IMT were not. The age‐related increase in mean IMT was more pronounced in the low HDL subjects than the control subjects (P < 0·01 for difference between elevations of age vs. IMT slopes). There were no differences in central pressure augmentation, the augmentation index, peripheral or central blood pressures between the groups.

Conclusions A low HDL‐C concentration is associated with thickening of carotid IMT independent of other risk factors in healthy affected members of low HDL families.
Enhancement of allergic skin wheal responses in patients with atopic eczema/dermatitis syndrome by playing video games or by a frequently ringing mobile phone
Authors: Kimata H.
Published: June 2003

Background Playing video games causes physical and psychological stress, including increased heart rate and blood pressure and aggression‐related feelings. Use of mobile phones is very popular in Japan, and frequent ringing is a common and intrusive part of Japanese life. Atopic eczema/dermatitis syndrome is often exacerbated by stress. Stress increases serum IgE levels, skews cytokine pattern towards Th2 type, enhances allergen‐induced skin wheal responses, and triggers mast cell degranulation via substance P, vasoactive intestinal peptide and nerve growth factor.

Materials and methods (1) In the video game study, normal subjects (n = 25), patients with allergic rhinitis (n = 25) or atopic eczema/dermatitis syndrome (n = 25) played a video game (STREET FIGHTER II) for 2 h. Before and after the study, allergen‐induced wheal responses, plasma levels of substance P, vasoactive intestinal peptide and nerve growth factor, and in vitro production of total IgE, antihouse dust mite IgE and cytokines were measured. (2) In the mobile phone study, normal subjects (n = 27), patients with allergic rhinitis (n = 27) or atopic eczema/dermatitis syndrome (n = 27) were exposed to 30 incidences of ringing mobile phones during 30 min. Before and after the study, allergen‐induced wheal responses, plasma levels of substance P, vasoactive intestinal peptide and nerve growth factor were measured.

Results Playing video games had no effect on the normal subjects or the patients with allergic rhinitis. In contrast, playing video games significantly enhanced allergen‐induced skin wheal responses and increased plasma levels of substance P, vasoactive intestinal peptide and nerve growth factors in the patients with atopic eczema/dermatitis syndrome. Moreover, playing video games enhanced in vitro production of total IgE and anti‐house dust mite IgE with concomitant increased production of IL‐4, IL‐10 and IL‐13 and decreased production of IFN‐γ and IL‐12 in the patients with atopic eczema/dermatitis syndrome. However, exposure to frequently ringing mobile phones significantly enhanced allergen‐induced skin wheal responses, plasma levels of substance P, vasoactive intestinal peptide and nerve growth factors in the patients with atopic eczema/dermatitis syndrome, but not in the normal subjects or the patients with allergic rhinitis.

Conclusion Playing video games enhanced allergic responses with a concomitant increased release of substance P, vasoactive intestinal peptide and nerve growth factor, and skewing of the cytokine pattern toward Th2 type in the patients with atopic eczema/dermatitis syndrome. In addition, exposure to frequently ringing mobile phones also enhanced allergic responses with a concomitant increased release of substance P, vasoactive intestinal peptide and nerve growth factor Collectively, high technology causes stress, which in turn may aggravate symptoms of atopic eczema/dermatitis syndrome.
International clinical placements for undergraduate students
Authors: Grant Elizabeth , Mckenna Lisa
Published: June 2003

• This paper reports the findings of a study that sought to gain insight into the experiences of third year nursing students who participated in a 4‐week clinical placement in an international setting.

• This study is different from many studies describing international placements for undergraduate nursing students as it concentrates on clinical experiences on placement.

• Students' reflective journals and face‐to‐face discussions were used to collect data, which were analysed by thematic content analysis.

• Categories were identified describing a focus on micro clinical‐based issues that expanded over time to a focus on broader issues reflecting the ‘nursing culture’ of the placement. Students described both positive and negative aspects of being placed in an international clinical setting, with the concept of ‘being different’ emerging.

• Whilst the findings cannot be generalized beyond the sample, the study highlights the importance of adequate preparation and support for students on international clinical placements, with emphasis on attention to clinical detail.
Demand for nursing competencies: an exploratory study in Taiwan's hospital system
Authors: Tzeng Huey‐Ming , Ketefian Shaké
Published: June 2003

• Along with increasing complexity of nursing services, hospital employers are demanding qualified and competent staff nurses for high quality clinical care. In Taiwan, disparities in the demand for competent nurses by employers and the supply produced by nursing educators still exist and require attention. A comprehensive understanding of the specific needs of Taiwan's medical care system for nursing services would help bridge the current gap between demand for and supply of competently trained nurses.

• This exploratory study investigated hospital employers' perceptions of the extent to which the nursing skills identified by Cleary et al. [Image: Journal of Nursing Scholarship (1998)20(4):39–42] were needed for staff nurses in Taiwan's medical care system. There were a total of 21 nursing competencies and classification on these items was also implemented.

• A cross‐sectional, quantitative, survey design was conducted. Subjects' participation was voluntary, an information leaflet and an informed consent form was included in the questionnaire. A total of 89 nursing employers (nursing directors, associate directors, supervisor, or head nurse) participated, resulting in a 42.6% response rate.

• Factor analysis grouped these skills into three factors: basic‐level patient care, intermediate‐level patient care and basic management, and advanced‐level patient care and supervision. This study confirmed that levels of nursing competencies needed differed by type of hospital accreditation. These levels also varied depending on types of services provided, employers' professional titles and tenure of currently employed nurses.

• The questionnaire developed for this study could be used as one of the tools to communicate demand and supply of nursing competencies between nurse educators and employers. These competencies could be used to develop a checklist for evaluating adequacy of nursing programmes in order to meet nurses' new roles and responsibilities and improve nursing care quality in the fast‐changing health care environment in Taiwan.
The experience of sexuality for individuals living with multiple sclerosis
Authors: Gagliardi Barbara A.
Published: June 2003

• Little is known of the experience of sexuality among people living with multiple sclerosis (MS).

• This Roy Adaptation Model‐based study focused on identifying the experiences of sexuality reported by individuals living with MS.

• A qualitative, naturalistic case study method was employed.

• Five women and three men diagnosed with MS were interviewed by telephone three times over a period of 1 year. The telephone interview guide consisted of a series of structured questions.

• Analysis of the telephone interview transcripts revealed three themes. The theme, ‘How I Feel About My Appearance’, reflected elements of the Roy model physiological, self‐concept, role function and interdependence modes. The theme, ‘I Have Feelings About My Sexuality’, reflected the self‐concept and interdependence modes, and the theme, ‘Sexuality For Me Has Both Negative and Positive Emotions’, reflected the self‐concept and interdependence modes.

• The small sample size precludes generalization of the results to all individuals living with MS.

• Nurses and other health care providers need to recognize that sexuality is an important issue for individuals with MS. Researchers should continue to examine experiences of sexuality in a larger sample of individuals with MS and also should begin to examine the effects of nursing interventions, such as support groups and individual counselling, on feelings about sexuality in individuals with MS.
‘It's like an explosion in your life…': lay perspectives on stress and myocardial infarction
Authors: Clark Alex M.
Published: June 2003

• Psychological difficulties are common after myocardial infarction (MI). These difficulties are most often represented to patients through cardiac rehabilitation services and the literature offered to patients after MI as being related to ‘stress’ and its management. However, no research has examined what MI patients understand by the term ‘stress’ or how congruent lay views of stress are with those evident in the professional literature.

• The aim of the study reported here was to examine post‐MI patients' views of stress, its functioning and relationship to their MI.

• As patients' views of stress were sought, qualitative interviews were used. A philosophical approach was taken (critical realism) that recognizes the legitimacy of both professional and lay perspectives. Data were generated in 44 semistructured interviews with 14 MI patients who were interviewed 48 hours, 1 week, 1 month and 3 months after hospital admission.

• While participants described their experiences after MI as being difficult, to convey this they used everyday terms such as fear, fright and worry. Rather than viewing stress as being a consequence of their MI, they perceived it to be a common cause of heart problems.

• Many considered stress as having a more influential role than other risk factors, such as smoking and diet. They expressed a wide variety of sophisticated and diverse views of stress and its functioning. Each of these views placed different weighting on the roles of social, personal and situational factors in contributing to the stressful reaction. Parallels were apparent between these lay accounts and theories of stress developed in the professional literature.
Medication calculation skills of nurses in Finland
Authors: Grandell‐Niemi Heidi , Hupli Maija , Leino‐Kilpi Helena , Puukka Pauli
Published: June 2003

• The aim of this study was to describe the medication calculation skills of nurses in Finland. We tried to ascertain how nurses evaluate their own medication calculation skills and how these self‐evaluations are associated with various background factors and the actual level they score in a calculation test.

• In the spring of 2000, nurses (n = 546) in one Finnish university hospital completed a questionnaire specially developed for this study. The instrument included structured questions, statements and a medication calculation test. The response rate was 56%. Data analysis was based on descriptive statistics.

• The nurses found the mathematics and dosage calculation easy and interesting but the pharmacology difficult. They evaluated their own mathematical and dosage calculation skills as sufficient, although it had certain shortcomings.

• The youngest nurses (20–29 years) evaluated their mathematical and dosage calculation skills as sufficient and they also succeeded in the calculation test. Basic (High School) education was associated with better calculation skills.

• The findings of this study support the need and importance of checking and maintaining one's medication calculation skills.