bluuebunny/crossref_metadata_2025 huggingface dataset:
Release of BDNF and GABA in the dorsal horn of neuropathic rats
Authors: Lever Isobel , Cunningham Joanna , Grist John , Yip Ping K. , Malcangio Marzia
Published: September 2003

Damage to peripheral nerves is associated with changes in excitability and/or phenotype of primary afferent neurons as well as increased neuronal excitability (central sensitization) and reduced inhibitory tone in the dorsal horn. For instance, in dorsal root ganglia (DRG) brain derived neurotrophic factor (BDNF) is down‐regulated in small cells whilst de novo expressed in large diameter cells. In the dorsal horn, GABA content is decreased. In this study, in a dorsal horn, ‘with dorsal roots attached’ preparation obtained from spinal nerve lesioned Wistar rats, stimulation of ipsilateral dorsal roots at either A fibre or A + C fibre strength did not evoke release of BDNF. In separate experiments, activity‐induced release of GABA in the isolated dorsal horn of neuropathic rats was significantly reduced compared to release in sham operated rats. GABA release could be significantly restored following topical application of BDNF through the dorsal horn preparation. Finally, neuropathic rats developed thermal and mechanical hypersensitivity and thermal hyperalgesia was reduced by intrathecal injection of BDNF. We concluded that BDNF‐induced release of GABA could be a mechanism to explain the antinociceptive action of intrathecal BDNF in neuropathic animals. Furthermore, reduced availability of sensory neuron‐derived BDNF might contribute to the reduced GABAergic tone in the dorsal horn of neuropathic rats.
Dopamine efflux in nucleus accumbens shell and core in response to appetitive classical conditioning
Authors: Cheng J. J. , De Bruin J. P. C. , Feenstra M. G. P.
Published: September 2003

Dopamine transmission within the nucleus accumbens has been implicated in associative reinforcement learning. We investigated the effect of appetitive classical conditioning on dopamine efflux in the rat nucleus accumbens shell and core, as dopamine may be differentially activated by conditioned and unconditioned stimuli (CS, US) in these subregions. After implantation of microdialysis cannulae, rats were food restricted and trained for three consecutive days with three acquisition sessions per day. A 10‐s noise (CS) was immediately followed by the delivery of two reward pellets (US) for the conditioned group (paired presentation), whereas conditioned stimuli and unconditioned stimuli were presented at random for the control group (unpaired presentation). On the fourth day, all rats were given a further CS + US session and two CS‐alone sessions, and extracellular dopamine concentrations were measured (7.5 min/per sample). Behavioural measures (number of nose pokes, latency to nose poke after conditioned stimuli onset, locomotor activity) demonstrated that the paired groups showed a high level of conditioning. CS + US presentation increased dopamine equally in both shell and core of the paired and unpaired groups. CS alone presentation induced a conditioned dopamine release only in the paired groups. No significant difference was found between shell and core. Unlike previous conditioning paradigms involving either a more salient US (foot shock, addictive drug) or a more complex CS, the present paradigm, using normal reward pellets as US and a discrete auditory stimulus as CS, did not lead to differential responses in dopamine efflux in shell and core subregions of the nucleus accumbens.
Expression of NMDA receptor NR1, NR2A and NR2B subunit mRNAs during development of the human hippocampal formation
Authors: Law Amanda J. , Weickert Cynthia Shannon , Webster Maree J. , Herman Mary M. , Kleinman Joel E. , Harrison Paul J.
Published: September 2003

The N‐methyl‐d‐aspartate receptor plays a critical role in the formation and maintenance of synapses during brain development. In the rodent, changes in subunit expression and assembly of the heteromeric receptor complex accompany these maturational processes. However, little is known about N‐methyl‐d‐aspartate receptor subunit expression during human brain development. We used in situ hybridization to examine the distribution and relative abundance of NR1, NR2A and NR2B subunit messenger ribonucleic acids in the hippocampal formation and adjacent cortex of 34 human subjects at five stages of life (neonate, infant, adolescent, young adult and adult). At all ages, the three messenger ribonucleic acids were expressed in all subfields, predominantly by pyramidal neurons, granule cells and polymorphic hilar cells. However, their abundance varied across ontogeny. Levels of NR1 messenger ribonucleic acid in CA4, CA3 and CA2 subfields were significantly lower in the neonate than all other age groups. In the dentate gyrus, subiculum and parahippocampal gyrus, NR2B messenger ribonucleic acid levels were higher in the neonate than in older age groups. NR2A messenger ribonucleic acid levels remained constant, leading to an age‐related increase in NR2A/2B transcript ratio. We conclude that N‐methyl‐d‐aspartate receptor subunit messenger ribonucleic acids are differentially expressed during postnatal development of the human hippocampus, with a pattern similar but not identical to that seen in the rodent. Changes in subunit composition may thus contribute to maturational differences in human hippocampal N‐methyl‐d‐aspartate receptor function, and to their role in the pathophysiology of schizophrenia and other neurodevelopmental disorders.
Post‐natal development of type 1 cannabinoid receptor immunoreactivity in the rat hippocampus
Authors: Morozov Yury M. , F. Freund Tamás
Published: September 2003

Type 1 cannabinoid receptors, selectively located on axon terminals of GABAergic interneurons in the hippocampus, are known to be involved in endocannabinoid‐mediated retrograde synaptic signalling. The question arises whether type 1 cannabinoid receptors appear on these axons during early post‐natal life, when GABAergic transmission is still depolarizing, and whether there are any developmental changes in the cellular or subcellular expression pattern. Here we demonstrate, using single and double immunocytochemical methods at the light and electron microscopic levels, that type 1 cannabinoid receptors are expressed only on the membrane of axon terminals and pre‐terminal axons but not on the soma‐dendritic membrane at all examined timepoints between post‐natal days 0 and 20, similar to the adult distribution. All type 1 cannabinoid receptor‐positive boutons formed symmetric synapses. Granular labelling in the somata was already strong at post‐natal day 0 and corresponded to multivesicular bodies, lysosomes, Golgi apparatus and rough endoplasmic reticulum. The type 1 cannabinoid receptor‐positive axons were shown to originate largely from cholecystokinin‐immunoreactive basket and bistratified neurons throughout the hippocampus (90% of all type 1 cannabinoid receptor‐containing cells) and dentate gyrus (70% of all type 1 cannabinoid receptor‐containing cells). The remaining cells have not been identified but probably belong to the somatostatin‐ and/or neuropeptide Y‐containing subsets, as cholecystokinin‐negative, type 1 cannabinoid receptor‐positive axons have been observed in strata moleculare and lacunosum‐moleculare of the dentate gyrus and CA1–3, respectively, where these neurons are known to arborize. No cell types were found that expressed type 1 cannabinoid receptors transiently at some developmental stage. We conclude that the cellular and subcellular pattern of type 1 cannabinoid receptor expression during early post‐natal life is similar to the adult pattern and type 1 cannabinoid receptors are expressed on the cholecystokinin‐containing axons as soon as synapse formation begins. This suggests that retrograde synaptic signalling by endocannabinoids is required for the normal operation of GABAergic neurotransmission even before it becomes hyperpolarizing.
Spatial channels of visual processing in cortical blindness
Authors: Sahraie Arash , Trevethan Ceri T. , Weiskrantz Lawrence , Olson John , MacLeod Mary Joan , Murray Alison D. , Dijkhuizen Roelf S. , Counsell Carl , Coleman Richard
Published: September 2003

Blindsight is the ability of some cortically blind patients to discriminate visual events presented within their field defect. We have examined a fundamental aspect of visual processing, namely the detection of spatial structures presented within the field defect of 10 cortically blind patients. The method outlined is based on the detection of high‐contrast stimuli and is effective in flagging a ‘window of detection’ in the spatial frequency spectrum, should it exist. Here we report on the presence of a narrowly tuned psychophysical spatial channel optimally responding to frequencies less than 4 cycles/° in eight out of 10 patients tested. The two patients who did not show any evidence of blindsight appear to have intact midbrain structures, but have lesions that extend from the occipital cortex to the thalamus. In addition, we have recorded subjective reports of awareness of the visual events in each trial. Detection scores of eight blindsight patients were subsequently subdivided based on the subjective reports of awareness. It appears that the psychophysical spatial channel‐mediating responses in the absence of any awareness of the visual event have a narrower frequency response than those involved when the patients report some awareness of the visual event. The findings are discussed in relation to previous reports on the incidence of blindsight and performance on tasks involving spatial processing.
Amygdala and anterior cingulate cortex activation during affective startle modulation: a PET study of fear
Authors: Pissiota Anna , Frans Örjan , Michelgård Åsa , Appel Lieuwe , Långström Bengt , Flaten Magne Arve , Fredrikson Mats
Published: September 2003

The human startle response is modulated by emotional experiences, with startle potentiation associated with negative affect. We used positron emission tomography with15O‐water to study neural networks associated with startle modulation by phobic fear in a group of subjects with specific snake or spider phobia, but not both, during exposure to pictures of their feared and non‐feared objects, paired and unpaired with acoustic startle stimuli. Measurement of eye electromyographic activity confirmed startle potentiation during the phobic as compared with the non‐phobic condition. Employing a factorial design, we evaluated brain correlates of startle modulation as the interaction between startle and affect, using the double subtraction contrast (phobic startle vs. phobic alone) vs. (non‐phobic startle vs. non‐phobic alone). As a result of startle potentiation, a significant increase in regional cerebral blood flow was found in the left amygdaloid–hippocampal region, and medially in the affective division of the anterior cingulate cortex (ACC). These results provide evidence from functional brain imaging for a modulatory role of the amygdaloid complex on startle reactions in humans. They also point to the involvement of the affective ACC in the processing of startle stimuli during emotionally aversive experiences. The co‐activation of these areas may reflect increased attention to fear‐relevant stimuli. Thus, we suggest that the amygdaloid area and the ACC form part of a neural system dedicated to attention and orientation to danger, and that this network modulates startle during negative affect.
Cyclic AMP response element‐binding (CREB)‐like proteins in a molluscan brain: cellular localization and learning‐induced phosphorylation
Authors: Ribeiro Maria J. , Serfőző Zoltán , Papp Andrea , Kemenes Ildikó , O'Shea Michael , Yin Jerry C. P. , Benjamin Paul R. , Kemenes György
Published: September 2003

The phosphorylation and the binding to DNA of the nuclear transcription factor, cyclic adenosine 3′,5′‐monophosphate (cAMP) response element‐binding protein (CREB) are conserved key steps in the molecular cascade leading to the formation of long‐term memory (LTM). Here, we characterize, for the first time, a CREB1‐like protein in the central nervous system (CNS) of Lymnaea, a model system used widely for the study of the fundamental mechanisms of learning and memory. We demonstrate cAMP response element (CRE)‐binding activity in CNS protein extracts and show that one of the CRE‐binding proteins is recognized by a polyclonal antibody raised to mammalian (human) CREB1. The same antibody detects specific CREB1 immunoreactivity in CNS extracts and in the nuclei of most neurons in the brain. Moreover, phospho–CREB1‐specific immunoreactivity is increased significantly in protein extracts of the CNS by forskolin, an activator of adenylate cyclase. The forskolin‐induced increase in phospho–CREB1 immunoreactivity is localized to the nuclei of CNS neurons, some of which have an important role in the formation of LTM. Significantly, classical food–reward conditioning increases phospho–CREB1 immunoreactivity in Lymnaea CNS protein extracts. This increase in immunoreactivity is specific to the ganglia that contain the feeding circuitry, which undergoes cellular changes after classical conditioning. This work establishes the expression of a highly conserved functional CREB1‐like protein in the CNS of Lymnaea and opens the way for a detailed analysis of the role of CREB proteins in LTM formation in this model system.
Modulation of electroencephalographic responses to transcranial magnetic stimulation: evidence for changes in cortical excitability related to movement
Authors: Nikulin Vadim V. , Kičić Dubravko , Kähkönen Seppo , Ilmoniemi Risto J.
Published: September 2003

Transcranial magnetic stimulation (TMS) and multichannel electroencephalography (EEG) were used for the investigation of cortical excitability preceding voluntary movement in human subjects. The study showed the practical value of the combined TMS–EEG approach in differentiating between cortical and spinal‐cord mechanisms, which is difficult with conventional electromyographic measures alone. TMS induced a pronounced negativity (N100) lasting for 150–200 ms, with the amplitude maximum in the stimulated hemisphere. When TMS was applied just before the onset of the visually triggered movement, N100 was markedly attenuated, although motor evoked potentials (MEPs) became larger. We suggest that the N100 component represents an inhibitory response following TMS. This interpretation is in agreement with intracellular recordings in animals, paired‐pulse TMS studies and experiments showing increased premovement excitability on the basis of MEPs. N100 was not affected only by the subsequent movement, but also by the switching from rest to the motor‐task condition, which caused a slight attenuation of the N100 component; no changes, however, were found in the amplitude of MEPs, suggesting that modified excitability did not affect the output of the corticospinal pyramidal cells. By contrast to MEPs, N100 was modulated also by the presentation of the visual stimulus alone, i.e. when no movement was required. This attenuation suggests that even in a rest condition visual stimuli have an access to the sensorimotor regions of the cortex, most probably through ascending arousal brain systems.
Regulation of DARPP‐32 Thr75 phosphorylation by neurotensin in neostriatal neurons: involvement of glutamate signalling
Authors: Matsuyama Seiichiro , Fukui Ryuichi , Higashi Hideho , Nishi Akinori
Published: September 2003

Neurotensin is a neuropeptide involved in dopaminergic signalling. We have recently reported that neurotensin stimulates the phosphorylation of DARPP‐32 (dopamine‐ and cAMP‐regulated phosphoprotein of Mr 32 kDa) at Thr34 (PKA‐site) by activating dopamine D1‐type receptors in neostriatal neurons. DARPP‐32 is also phosphorylated by cyclin‐dependent kinase 5 on Thr75, and the phosphorylated form of DARPP‐32 at Thr75 inhibits protein kinase (PKA) activity. In this study, we examined the effect of neurotensin on DARPP‐32 Thr75 phosphorylation using mouse neostriatal slices. Neurotensin decreased the level of phospho‐Thr75 DARPP‐32 at 2 min of incubation, maximally to about 50% of control at a concentration of 1 µm. Pretreatment with a combined neurotensin receptor type 1 (NTR1)/type 2 (NTR2) antagonist, SR142948, reduced the basal level of phospho‐Thr75 DARPP‐32 and abolished the ability of neurotensin to decrease DARPP‐32 Thr75 phosphorylation. However, neither an NTR1 antagonist, SR48692, an NTR2 antagonist, levocabastine, nor the two combined affected the basal level and the neurotensin‐mediated decrease in DARPP‐32 Thr75 phosphorylation. The effect of neurotensin was abolished by tetrodotoxin (TTX) or MK801 plus CNQX, but not by SCH23390 or raclopride. These results indicate that neurotensin stimulates the release of glutamate by activating a hypothesized unidentified neurotensin receptor, resulting in the dephosphorylation of DARPP‐32 at Thr75 by activating NMDA and AMPA receptors expressed at medium spiny neurons. Thus, neurotensin, by removing the inhibition of PKA by phospho‐Thr75 DARPP‐32, potentiates its signalling via the dopamine/D1 receptor/PKA/phospho‐Thr34 DARPP‐32/PP‐1 cascade.
Occlusion of the right subclavian artery after insertion of a transoesophageal echocardiography probe in a neonate
Authors: Koinig Herbert , Schlemmer Michael , Keznickl Franz P.
Published: September 2003

We present a case of occlusion of the right arm's blood supply in a neonate with a lusorian artery, a rare anomaly of the right subclavian artery, after insertion of a transoesophageal echocardiography (TOE) probe and discuss the impact of a lusorian artery on intraoperative TOE monitoring.
Anaesthetic consequences for a child with complex multilevel airway obstruction – recommendations for avoiding life‐threatening sequelae
Authors: Dilworth Kelly , Thomas Jenny
Published: September 2003

A boy with a suspected lymphoid malignancy presented with gross head and neck lymphadenopathy, a middle mediastinal mass, and rapidly worsening airway obstruction. General anaesthesia was required for definitive histopathological diagnosis. The combination of nasopharyngeal obstruction, malignant infiltration of the tonsils and pharynx, laryngeal displacement, and potential tracheal compression put this patient at extreme risk for perioperative airway complications. Risk assessment, and the impact of anaesthesia on pharyngeal neuromechanical function and mediastinal masses are discussed. Caution with volatile anaesthetic agents is recommended in the patient with an inherently unstable pharynx and/or trachea, in whom airway patency relies on a spontaneously breathing technique and intact airway reflexes.
Use of erythropoietin for bloodless surgery in a Jehovah's witness infant
Authors: Pérez‐Ferrer A. , De Vicente J. , Gredilla E. , García‐Vega M. I. , Bourgeois P. , Goldman L. J.
Published: September 2003

Summary We present a case of surgery in a 2‐month‐old infant of the Jehovah's Witness (JW) faith weighing 2.8 kg scheduled for left upper lobectomy because of congenital lobar emphysema. He presented with physiological anaemia (haematocrit 33.8%) in accordance with his age. Because of the relative emergency of surgery, a short erythropoietin course was instituted. Recombinant human erythropoietin (rHuEPO) at a dosage of 180 U·kg−1·day−1 was administered for 10 days preoperatively and for 4 days postoperatively. Iron was administered orally and intravenously over the entire perioperative period. No side‐effects from either erythropoietin or intravenously administered iron were observed. To our knowledge, this is the first case published of a short perioperative rHuEPO course in an infant.
Anaesthesia for a child with Walker–Warburg syndrome
Authors: Sahajananda H. , Meneges Jeevan
Published: September 2003

Summary Walker–Warburg syndrome (WWS) is a rare lethal autosomal recessive disorder manifested by characteristic central nervous system and eye malformations. We have not come across reports of general anaesthesia in a child with WWS in the English literature. We report a case of general anaesthesia in a 12‐month‐old male child with WWS. The child also had bilateral cleft lip, cleft palate, urogenital malformation and hydronephrosis. Despite many potential anaesthesia concerns, anaesthesia was uneventful in this child.
Nonopioid additives to local anaesthetics for caudal blockade in children: a systematic review
Authors: Ansermino Mark , Basu Rahul , Vandebeek Christine , Montgomery Carolyne
Published: September 2003

Background:  Caudal epidural injection with local anaesthetics is a popular regional technique used in infants and children. A disadvantage of caudal blockade is the relatively short duration of postoperative analgesia. Opioids have traditionally been added to increase the duration of analgesia but have been associated with unacceptable side‐effects. A number of nonopioid additives have been suggested to increase the duration of analgesia.

Methods:  A systematic review was conducted to identify randomized control trials comparing the use of local anaesthetic to local anaesthetic with nonopioid additives for caudal blockade in children. The increase in duration of analgesia and side‐effects were compared.

Results:  The addition of clonidine to the local anaesthetic solution produces an increase in the duration of analgesia following caudal blockade in children (pooled weighted mean difference of 145 min with 95% confidence interval of 132–157 min). Side‐effects include sedation and the potential for neonatal respiratory depression. Ketamine and midazolam further increase the duration of analgesia, however, the potential for neurotoxicity remains a concern.

Conclusion:  The evidence examined shows an increased duration of analgesia with clonidine, ketamine and midazolam. However, we are not convinced that the routine use of these adjuvants in the setting of elective outpatient surgery shows improved patient outcome. It is unclear if the potential for neurotoxicity is outweighed by clinical benefits. Further testing, including large clinical trials, is required before recommending routine use of nonopioid additives for caudal blockade in children.
Lingual oedema associated with the prolonged use of an inappropriately large laryngeal mask airway (LMATM) in an infant
Authors: Stillman Philip C.
Published: September 2003

A case report is presented of a 12‐month‐old infant who developed lingual oedema after the prolonged use of an inappropriately large laryngeal mask airway (LMATM). A size 2½ LMA was used in a 10.6 kg infant during a 5 h operative procedure. Postoperatively, the patient developed significant tongue oedema, which gradually resolved with time and dexamethasone treatment. This rare complication demonstrates the potential danger of using an overly large LMA in an infant, especially for a significant period of time.
Analgesic efficacy and tolerability of ketoprofen lysine salt vs paracetamol in common paediatric surgery. A randomized, single‐blind, parallel, multicentre trial
Authors: Messeri Andrea , Busoni Paolo , Noccioli Bruno , Murolo Sandro , Ivani Giorgio , Grossetti Roberto , Gallini Carla , Maestri Luciano , Fedele Guido , Novellini Roberto
Published: September 2003

Background: In this study, we compared the analgesic efficacy of ketoprofen lysine salt (OKi® suppositories) vs paracetamol, in children undergoing minor surgery. We also studied the side‐effects of the treatment.

Methods: Eighty‐five children of both sexes, aged 6–14 years, were enrolled in a multicentre, randomized, single‐blind, parallel‐group study design. In all patients postsurgical pain was evaluated by visual analogue scale (VAS) and degree of distress (night‐time awakening, crying, behaviour and defence posture).

Results: Ketoprofen lysine was more effective than paracetamol in reducing postoperative pain (P = 0.008) with earlier onset and longer duration (8 h) of the antinociceptive effect. Evaluation of area under the curve, an aggregated measure of VAS, and of distress, confirm the time profile of pain reduction. No adverse effects related to the treatment were observed.

Conclusions: Ketoprofen lysine salt can be considered a potent therapeutic approach to control postsurgery pain in children, and an alternative to other established drug regimens.
Assessing behaviour in children emerging from anaesthesia: can we apply psychiatric diagnostic techniques?
Authors: Przybylo H.J. , Martini D.R. , Mazurek A.J. , Bracey E. , Johnsen L. , Coté C.J.
Published: September 2003

Background: No standardized instrument exists for the systematic analysis of emergence behaviour in children after anaesthesia. Our purpose was to evaluate children's behaviour prior to anaesthetic induction and immediately upon emergence to develop an assessment tool using psychiatric terminology and techniques.

Methods: This prospective study evaluated 25 children from 2 to 9 years of age for preanaesthetic psychosocial factors that might affect behaviour. Children's behaviour was observed from admission to the surgical unit through the induction of anaesthesia. All children received a standardized premedication and induction of anaesthesia. The maintenance anaesthetic was randomized to intravenous remifentanil or inhaled isoflurane. All children underwent repair of strabismus. We assessed the behaviour of children for 30 min upon emergence from anaesthesia for symptoms of pain, distress and delirium using an assessment tool we developed guided by the principles of psychiatry as described in Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV).

Results: Using our assessment tool, 44% of children demonstrated altered behaviour on emergence; 20% demonstrated complex symptoms with characteristics of delirium. Children anaesthetized with isoflurane had significantly higher postanaesthesia behaviour assessment scores than those anaesthetized with remifentanil (P = 0.04). Age was a significant variable; children <62 months were more prone to altered behaviour than those >62 months (P = 0.02). Scores did not correlate with preanaesthetic risk factors including preexisting psychological or social variables or observed preanaesthetic distress. There was no delay in hospital discharge in children assessed as having altered behaviour.

Conclusions: This exploratory study suggests that postanaesthetic behaviour abnormalities with characteristics of distress or delirium can be categorized using known DSM‐IV terminology; in our cohort this behaviour was dependent on age and anaesthetic technique.
Efficacy and safety of continuous intravenous infusion of remifentanil in preterm infants undergoing laser therapy in retinopathy of prematurity: clinical experience
Authors: Sammartino M. , Bocci M.G. , Ferro G. , Mercurio G. , Papacci P. , Conti G. , Lepore D. , Molle F.
Published: September 2003

Background: Preterm infants often require surgery. As experimental evidence suggests that premature infants may experience pain and this could even result in fatal complications, the anaesthesiologist must face problems related to lowbirth weight, high risk of hypothermia, concomitant pulmonary disease and metabolic and receptor immaturity. Recently remifentanil has been considered an optimal analgesic drug in a preterm infant undergoing mechanical ventilation and frequent surgical manoeuvres, but no clinical studies have been reported in the literature. The aim of our study was to evaluate the efficacy of a continuous intravenous infusion of remifentanil in premature infants undergoing laser therapy for retinopathy of prematurity (ROP).

Methods: Six premature infants with ROP were scheduled for laser therapy. The procedure was performed in the neonatal intensive care unit. Transcutaneous carbon dioxide, pulse oximetry, respiratory rate, ECG and noninvasive blood pressure were continuously monitored. Infusion of remifentanil started with a dose of 0.75–1 μg·kg−1·min−1, 1 h before surgery. A midazolam bolus dose (0.20 mg·kg−1) was administered and the remifentanil infusion was increased to 3–5 μg·kg−1·min−1 taking into account haemodynamic and respiratory changes or spontaneous movements.

Results: Increased dosage was necessary only for 10 min during the procedure. No changes in temperature and ventilatory settings were observed and after 2 h from the surgical procedure the preterm infants were back to their preoperative status.

Conclusions: A continuous infusion of remifentanil allowed optimal control of surgical stress and a return to preoperative status and ventilatory settings without side‐effects.
The intubation depth marker: the confusion of the black line
Authors: Goel Sunita , Lim Suan‐Ling
Published: September 2003

Background: Estimation of the correct depth of insertion of a tracheal tube (TT) in children is extremely important. Insertion of an excessive length may result in endobronchial intubation while an inadequate length of insertion may lead to accidental extubation.

Methods: We reviewed TTs commonly used in paediatric practice and also reviewed recommended guidelines for correct depth of insertion.

Results: Amongst the different brands of TTs used, there was a wide discrepancy in the placement of the intubation depth marker. This is important as the intubation depth marker is often used as a guideline for intubation.

Conclusions: For optimal placement we can rely on various formulae and manufacturers’ markings on the TTs. Clinical judgement, however, remains the cornerstone of optimal placement.
A French survey of paediatric airway management use in tonsillectomy and appendicectomy
Authors: Ecoffey Claude , Auroy Yves , Pequignot Françoise , Jougla Eric , Clergue François , Laxenaire Marie‐Claire , Lienhart André
Published: September 2003

Background: There are no epidemiological data describing tracheal intubation and laryngeal mask airway (LMATM) use in paediatric anaesthesia. This analysis focused on the factors leading to the indication for an airway management procedure, i.e. tracheal intubation and laryngeal mask airway vs face mask during general anaesthesia for tonsillectomy and appendicectomy.

Methods: The data were recorded in the French survey of Practical Anaesthesia performed in 1996. Two main types of surgical procedures were selected: tonsillectomy and appendicectomy because of the number of patients and the need to use an invasive airway management technique.

Results: During a 1‐year period, 627 anaesthetics for appendicectomy and 653 anaesthetics for tonsillectomy were recorded in the sample under consideration. Tracheal intubation or laryngeal mask airway was undertaken in 66% of tonsillectomies and 84% of appendicectomies. Univariate analysis showed that tracheal intubation/laryngeal mask were used significantly more often in older children, with long duration of anaesthesia, in nonambulatory procedures and in procedures performed at an academic centre. When these variables were included in a multivariate analysis, the duration of anaesthesia over 30 min was a factor linked to the use of tracheal intubation/laryngeal mask airway for the two types of surgery (P < 0.0001). For tonsillectomy, inpatients were 2.9 times more likely to be intubated (or have an laryngeal mask airway) than were outpatients. For appendicectomy, older children were 3.4 times more likely to be intubated (or have an laryngeal mask airway) than younger children.

Conclusions: This large French survey shows that the use of tracheal intubation/laryngeal mask airway in this country is primarily related to a predicted long duration of anaesthesia.
Paediatric intubation in Scottish emergency departments
Authors: Oglesby A.J. , Graham C.A. , Beard D. , McKeown D.W.
Published: September 2003

Background: Intubation of children in the emergency department setting is uncommon. This prospective observational study examines the practice of paediatric intubation in Scottish adult/paediatric urban emergency departments.

Methods: A prospective observational study of every intubation attempt was performed in seven urban Scottish emergency departments in 1999 and 2000. Children were defined as those patients who were less than 13 years of age on the day of presentation. Prehospital intubations were only included if they were performed by a mobile medical team doctor from one of the seven hospitals.

Results: A total of 1713 patients were identified, 44 of whom (2.6%) were children. The median age was 4 years (range 0–12 years), and 57% (25 of 44) of intubations were performed on patients with traumatic injuries. Emergency physicians attempted intubation in 27% (12 of 44) of cases, anaesthetists in 73% (32 of 44); 18% (eight of 44) of patients were intubated in nontraumatic cardiac arrest, 68% (30 of 44) underwent rapid sequence intubation (RSI), one (2%) had inhalational anaesthesia and 13 (30%) were intubated without drugs. Eighty per cent (35 of 44) of patients were intubated at the first attempt; eight patients required two attempts, and one required three attempts. Three children were intubated prehospital by mobile medical teams. Emergency physicians intubated more patients with ‘physiological compromise’ (100% vs 91%).

Conclusions: Paediatric intubation in the emergency department is uncommon. Collaboration and appropriate training for doctors in emergency medicine, anaesthesia and paediatrics is essential.
Anaesthetic implications of the child with Robinow syndrome
Authors: Sleesman Jay B. , Tobias Joseph D.
Published: September 2003

Robinow syndrome, originally described in 1969, consists of mesomelic brachymelia, short stature, genital hypoplasia and characteristic facies. Associated organ system involvement may include developmental delay, congenital heart disease, obstructive disorders of the urinary tract and renal cysts. As there is a potential for airway problems related to the facial features, such as midface hypoplasia and micrognathia, perioperative management of these patients is important. The authors present an 8‐year‐old boy, previously diagnosed with Robinow syndrome, who was admitted for an emergency surgical procedure. The perioperative implications of this disorder are reviewed.
Enhanced fungal resistance in transgenic cotton expressing an endochitinase gene from Trichoderma virens
Authors: Emani Chandrakanth , Garcia Juan Manuel , Lopata‐Finch Emily , Pozo Maria Jose , Uribe Pedro , Kim Dong‐Jin , Sunilkumar Ganesan , Cook Douglas R. , Kenerley Charles M. , Rathore Keerti S.
Published: September 2003

Mycoparasitic fungi are proving to be rich sources of antifungal genes that can be utilized to genetically engineer important crops for resistance against fungal pathogens. We have transformed cotton and tobacco plants with a cDNA clone encoding a 42 kDa endochitinase from the mycoparasitic fungus, Trichoderma virens. Plants from 82 independently transformed callus lines of cotton were regenerated and analysed for transgene expression. Several primary transformants were identified with endochitinase activities that were significantly higher than the control values. Transgene integration and expression was confirmed by Southern and Northern blot analyses, respectively. The transgenic endochitinase activities were examined in the leaves of transgenic tobacco as well as in the leaves, roots, hypocotyls and seeds of transgenic cotton. Transgenic plants with elevated endochitinase activities also showed the expected 42 kDa endochitinase band in fluorescence, gel‐based assays performed with the leaf extracts in both species. Homozygous T2 plants of the high endochitinase‐expressing cotton lines were tested for disease resistance against a soil‐borne pathogen, Rhizoctonia solani and a foliar pathogen, Alternaria alternata. Transgenic cotton plants showed significant resistance to both pathogens.
Flexible control of plant architecture and yield via switchable expression of Arabidopsis gai
Authors: Ait‐ali Tahar , Rands Carley , Harberd Nicholas P.
Published: September 2003

The growth of plants is repressed by DELLA proteins, nuclear regulators whose activities are opposed by the growth‐promoting phytohormone gibberellin (GA). Mutations affecting DELLA protein function were previously used by plant breeders to create the high‐yielding semidwarf wheat varieties of the green revolution. gai is an Arabidopsis mutant DELLA protein‐encoding orthologue of the wheat semidwarfing genes. Here we describe the development of a transgene that confers ethanol‐inducible gai expression. Transient induction of gai causes transient growth repression: growth prior to and after treatment is unaffected. Appropriate ethanol treatments result in dwarf plants that produce the same numbers of seeds as untreated controls. This new technology represents a substantial advance in the applicability of genes encoding mutant DELLA proteins to agricultural and horticultural improvement, enhancing the flexibity with which these genes can be used for the sustainable achievement of increased crop plant yields.
Identification of putative plant cold responsive regulatory elements by gene expression profiling and a pattern enumeration algorithm
Authors: Kreps Joel , Budworth Paul , Goff Steve , Wang Ronglin
Published: September 2003

A pattern enumeration algorithm named GBSSR has been developed to analyse co‐expressed gene groups identified through gene chip expression profiling to search for putative cis‐regulatory elements, an important step toward understanding transcriptional factors, quantitative trait loci and gene regulatory networks. Without making any statistical assumptions, this algorithm establishes the frequency distribution of all eligible 6–15 bp strings by extensive bootstrap sampling from an entire genome worth of promoters, enabling those over‐represented in a co‐expressed gene group to be identified. Using a well‐studied plant cold responsive gene system as a positive control, several known cold responsive elements were identified as top ranking candidates, along with some potentially novel ones. A typical analysis of 40 co‐expressed genes takes a relatively inexpensive Linux cluster with 32 × 1.4 GHz Intel CPUs about 7 days to process.
Engineering the root–soil interface via targeted expression of a synthetic phytase gene in trichoblasts
Authors: Zimmermann Philip , Zardi Gerardo , Lehmann Martin , Zeder Christophe , Amrhein Nikolaus , Frossard Emmanuel , Bucher Marcel
Published: September 2003

For biochemical modification of the root–soil interface, the engineered secretion of stable enzymes from trichoblasts (= root hair bearing rhizodermal cells) is proposed. As a reporter activity, we chose to express a synthetic gene encoding a secretory phytase (PHY) directed by a trichoblast‐specific promoter in root hair cells of the crop plant potato. Transgenic plants produced and secreted phytase in sufficient amounts to release phosphate from phytate in liquid medium. When grown in an unsterile substrate containing phytate, transgenic plants accumulated 40% more P in leaves than wild‐type plants. The improved P nutrition driven by trichoblast‐targeted expression and subsequent secretion of PHY illustrates the potential of using trichoblast‐targeted expression of suitable enzymes for future applications in plant nutrition, phytoremediation and molecular farming.
Reciprocal control of flowering time by OsSOC1 in transgenic Arabidopsis and by FLC in transgenic rice
Authors: Tadege Million , Sheldon Candice C. , Helliwell Chris A. , Upadhyaya Narayana M. , Dennis Elizabeth S. , Peacock W. James
Published: September 2003

In a screen for MADS box genes which activate and/or repress flowering in rice, we identified a gene encoding a MADS domain protein (OsSOC1) related to the Arabidopsis gene AtSOC1. AtSOC1 and OsSOC1 show a 97% amino acid similarity in their MADS domain. The rice gene contains a large first intron of 27.6 kb compared to the 1 kb intron in Arabidopsis. OsSOC1 is located on top of the short arm of chromosome 3, tightly linked to the heading date locus, Hd9. OsSOC1 is expressed in vegetative tissues, and expression is elevated at the time of floral initiation, 40–50 days after sowing, and remains uniformly high thereafter, similar to the expression pattern of AtSOC1. The constitutive expression of OsSOC1 in Arabidopsis results in early flowering, suggesting that the rice gene is a functional equivalent of AtSOC1. We were not able to identify FLC‐like sequences in the rice genome; however, we show that ectopic expression of the Arabidopsis FLC delays flowering in rice, and the up‐regulation of OsSOC1 at the onset of flowering initiation is delayed in the AtFLC transgenic lines. The reciprocal recognition and flowering time effects of genes introduced into either Arabidopsis or rice suggest that some components of the flowering pathways may be shared. This points to a potential application in the manipulation of flowering time in cereals using well characterized Arabidopsis genes.
Presence of potential allergy‐related linear epitopes in novel proteins from conventional crops and the implication for the safety assessment of these crops with respect to the current testing of genetically modified crops
Authors: Kleter Gijs A. , Peijnenburg Ad A. C. M.
Published: September 2003

Mitochondria of cytoplasmic male sterile crop plants contain novel, chimeric open reading frames. In addition, a number of crops carry endogenous double‐stranded ribonucleic acid (dsRNA). In this study, the novel proteins encoded by these genetic components were screened for the presence of potential binding sites (epitopes) of allergy‐associated IgE antibodies, as was previously done with transgenic proteins from genetically modified crops. The procedure entails the identification of stretches of at least six contiguous amino acids that are shared by novel proteins and known allergenic proteins. These stretches are further checked for potential linear IgE‐binding epitopes. Of the 16 novel protein sequences screened in this study, nine contained stretches of six or seven amino acids that were also present in allergenic proteins. Four cases of similarity are of special interest, given the predicted antigenicity of the identical stretch within the allergenic and novel protein, the IgE‐binding by a peptide containing an identical stretch reported in literature, or the multiple incidence of identical stretches of the same allergen within a novel protein. These selected stretches are present in novel proteins derived from oilseed rape and radish (ORF138), rice (dsRNA), and fava bean (dsRNA), and warrant further clinical testing. The frequency of positive outcomes and the sizes of the identical stretches were comparable to those previously found for transgenic proteins in genetically modified crops. It is discussed whether novel proteins from conventional crops should be subject to an assessment of potential allergenicity, a procedure which is currently mandatory for transgenic proteins from genetically modified crops.
What Kind of Habituation is Impaired in Migraine Patients?
Authors: Siniatchkin M , Kropp P , Gerber W-D
Published: September 2003

The acoustically evoked cortical potentials of 20 migraine patients were investigated using a combined conditioning-testing and oddball paradigm. The short and long-term habituation results of the P50 and P300 waves were compared with 16 healthy subjects. Migraineurs were characterized by a sensory gating deficit of the P50 wave (reduced short-term habituation) in the non-target condition and a reduced long-term habituation of the P300 wave in the target condition. The study describes disturbances of information processing on the automatic and cognitive levels in migraine patients and emphasizes the role of sensory gating and orienting response in migraine pathogenesis.
Placebo Response in Clinical Randomized Trials of Analgesics in Migraine
Authors: Bendtsen L , Mattsson P , Zwart J-A , Lipton RB
Published: September 2003

The objective was to assess the placebo response in randomized clinical trials of analgesics in the treatment of migraine attacks. We included placebo-controlled studies that used the criteria of the International Headache Society for the diagnosis of migraine and headache response as the primary efficacy parameter. In the 11 studies that qualified for inclusion, headache response occurred after placebo treatment in 7-50% of the migraineurs with an average placebo response rate of 30% (95% confidence interval (CI) 23-36). Two hours after treatment with placebo an average of 9% (95% CI 7-12, range 7-17%) of the patients were found to be pain free. In conclusion, the average headache response rate to placebo was 30% in randomized clinical trials of analgesics in migraine with a tremendous variation among studies. Placebo response rates vary with the choice of primary efficacy measure as well as patient characteristics and study design.
Ethical Aspects of Placebo in Migraine Research
Authors: Linde M , May A , Limmroth V , Dahlöf C ,   on behalf of the Headache Masters Programme
Published: September 2003

Randomized placebo-controlled clinical trials have been the ‘golden standard’ during the last decades in the development of new drug therapies. This scientifically valid approach has recently been questioned in the fifth revised version of the Declaration of Helsinki, which states that the use of placebo-controlled clinical trials is only acceptable when no proven treatment exists for the studied disease. The World Medical Association further claims that no national ethical, legal or regulatory requirements should be allowed to reduce or eliminate any of the statements in the declaration. In spite of this, the document is not generally accepted as the world ethical standard, as demonstrated by its lack of adoption by many professional associations. In the evaluation process for a drug to be approved in many countries today, clinical investigators at the hospitals and researchers at the pharmaceutical companies are obliged to use study protocols that would be rejected if the new declaration were to be fully adopted. Adherence to the clinical trial guidelines of the International Headache Society could also mean violation of the new Helsinki declaration of ethics. Some ethics committees have already adopted the new declaration, which has caused concern among clinical investigators, who find this document to be vastly out of the line with common practice. At the moment, the situation is unclear and debated with increasing polarity concerning the scientific and ethical issues regarding the use of placebo in clinical trials.
Placebo Adverse Events in Headache Trials: Headache as an Adverse Event of Placebo
Authors: Reuter U , Sanchez del Rio M , Carpay JA , Boes CJ , Silberstein SD ,   for the GSK Headache Masters Program
Published: September 2003

We analysed the adverse events of placebo in acute and preventive randomized, double-blind, placebo-controlled studies for migraine treatment. Fifty-seven trials (oral triptans, non-steroidal anti-inflammatory drugs, nasal ergot alkaloids and preventive agents) were included. From 10 to 30% of subjects reported adverse events after placebo. Most common were features associated with a migraine attack, such as nausea, phono- and photophobia. Other frequent complaints resembled those of the active drug (e.g. chest pressure in triptan trials). A third group of adverse events appeared to be coincidental (e.g. sleep disturbance). Adverse events following placebo are probably related to the drug under study and the symptomatology of migraine; some have no obvious explanation.