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We tested the hypothesis that induction of neuronal NO synthase (nNOS) impairs vascular smooth muscle contractility after hypoxia. nNOS protein was increased in aorta, mesenteric arterioles, pulmonary arteries, brain, and diaphragm from rats exposed to 8% O2 for 48 hours and in human aortic SMCs after hypoxic incubation (1% O2). Ca2+-dependent NO synthase activity was increased in endothelium-denuded aortic segments from hypoxia-exposed rats. NG-nitro-L-arginine methyl ester enhanced the contractile responses of endothelium-denuded aortic rings and mesenteric arterioles from hypoxia-exposed but not normoxic rats (P < 0.05). The hypoxia-inducible mRNA transcript expressed by human cells was found to contain a novel 5′-untranslated region, consistent with activation of transcription in the genomic region contiguous with exon 2. Translational efficiency of this transcript is markedly increased compared with previously described human nNOS mRNAs. Transgenic mice possessing a lacZ reporter construct under control of these genomic sequences demonstrated expression of the construct after exposure to hypoxia (8% O2, 48 hours) in the aorta, mesenteric arterioles, renal papilla, and brain. These results reveal a novel human nNOS promoter that confers the ability to rapidly upregulate nNOS expression in response to hypoxia with a functionally significant effect on vascular smooth muscle contraction.

Expression of the neuronal nitric-oxide synthase (nNOS) mRNA is subject to complex cell-specific transcriptional regulation, which is mediated by alternative promoters. Unexpectedly, we identified a 89-nucleotide alternatively spliced exon located in the 5'-untranslated region between exon 1 variants and a common exon 2 that contains the translational initiation codon. Alternative splicing events that do not affect the open reading frame are distinctly uncommon in mammals; therefore, we assessed its functional relevance. Transient transfection of reporter RNAs performed in a variety of cell types revealed that this alternatively spliced exon acts as a potent translational repressor. Stably transfected cell lines confirmed that the alternatively spliced exon inhibited translation of the native nNOS open reading frame. Reverse transcription-PCR and RNase protection assays indicated that nNOS mRNAs containing this exon are common and expressed in both a promoter-specific and tissue-restricted fashion. Mutational analysis identified the functional cis-element within this novel exon, and a secondary structure prediction revealed that it forms a putative stem-loop. RNA electrophoretic mobility shift assay techniques revealed that a specific cytoplasmic RNA-binding complex interacts with this motif. Hence, a unique splicing event within a 5'-untranslated region is demonstrated to introduce a translational control element. This represents a newer model for the translational control of a mammalian mRNA.

We compared the potency and duration of action of rocuronium in Chinese and Caucasian patients during general anesthesia. Thirty-six women (18 Caucasian and 18 Chinese) and 36 children (18 Caucasian and 18 Chinese) were evaluated during the administration of propofol/fentanyl anesthesia. Patients in each age group were randomized into three subgroups to receive single doses of 0.06, 0. 12, or 0.18 mg/kg rocuronium (adults) or 0.12, 0.18, or 0.24 mg/kg rocuronium (children). Neuromuscular blockade was assessed by electromyography of the adductor pollicis after train-of-four (TOF) stimulation of the ulnar nerve. Dose response curves were constructed when maximum neuromuscular depression of the first twitch of the train (T(1)) was obtained. A second bolus dose of rocuronium was then administered to a total dose of 0.6 mg/kg. The times of spontaneous recovery to T(1) 10%, 25%, and 90% of control and to TOF 0.25, 0.50, and 0.70 were recorded. For both adults and children, recovery occurred later in Chinese than in Caucasian patients (P

UNLABELLED We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. IMPLICATIONS These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.

The purpose of this study was to compare the mivacurium infusion requirements and neuromuscular recovery in adults and children during propofol/opioid and sevoflurane anesthesia. Seventy-five adult and 75 pediatric patients were randomized to receive propofol/opioid 0.5 or 1.0 minimum alveolar anesthetic concentration (MAC) (age-related) sevoflurane anesthesia. Plasma cholinesterase (PChE) activity was measured. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation every 10 s and adductor pollicis electromyography. A bolus of 2 x the 95% effective dose of mivacurium (0.25 mg/kg) was followed by an infusion titrated to maintain 90%-95% blockade. Mivacurium doses were recorded every 5 min. At the end of surgery, the infusion was stopped, and recovery from mivacurium was monitored until TOFor =0.7. PChE concentrations were within the normal range (adults 4-12 KU/L, children 6-16 KU/L) and correlated with mivacurium dose. Mivacurium infusion rates were higher in children than in adults: at 30 min, the rates in children were 13.1 +/- 6.4, 8.1 +/- 4.7, and 5.2 +/- 2.9 microg x kg(-1) x min(-1) at 0, 0.5, and 1.0 MAC sevoflurane, respectively; the corresponding rates in adults were 5.9 +/- 3.1, 4.3 +/- 1.7, and 2.9 +/- 0.7 microg x kg(-1) x min(-1) (P0.01). Sevoflurane decreased mivacurium requirements, maximal decreases at 45 min in children and 10 min in adults, and delayed neuromuscular function recovery. Children recovered twice as quickly as adults, achieving TOFor =0.7 at 9.8 +/- 2.5, 11.4 +/- 2.8, and 19.6 +/- 6.3 min compared with 19.9 +/- 5.4, 26.4 +/- 8.3, and 32.9 +/- 9.8 min in adults (P0.0001). In conclusion, mivacurium requirements were correlated with PChE, were greater in children than in adults, and were reduced by sevoflurane. Neuromuscular recovery occurred more rapidly in children and was delayed by sevoflurane.The mivacurium infusion requirement to maintain constant 90%-95% neuromuscular block during anesthesia is correlated with plasma cholinesterase activity. It is increased in children and reduced by the inhaled anesthetic sevoflurane. Despite the larger dose administered to children, recovery from block occurred more rapidly in children than in adults and was delayed by sevoflurane.

Midazolam has GABAergic effects in children that may modify propofol-induced involuntary movements, yet delay recovery. In a double-blind, randomized study, 24 children (2-7 yr of age, ASA physical status I or II) undergoing short surgical procedures received midazolam 0.5 mg/kg (Group M) or placebo (Group P) per os 20-30 min before propofol anesthesia (5 mg/kg intravenously followed by an infusion). Blind observers scored sedation and anxiety levels (scale 1-4) before premedication, at separation from parents, and at induction of anesthesia. Induction and emergence were videotaped, and body movements were recorded. During recovery, times to eye opening and maximum Steward (SS = 6) and Vancouver Sedative Recovery (VSRS = 22) scores were noted. Parents were questioned about side effects that may have occurred during the following week. Both groups were similar in age, sex, weight, timing of premedication, propofol dose, and duration of surgery. The incidence of involuntary movements did not differ between groups but was higher at induction (79%) than on emergence (25%) (P < 0.05). Anxiety and sedation scores were similar in Group P and Group M, but recovery took longer after midazolam, with eye opening (mean +/- SD) 24 +/- 7 vs 43 +/- 18 min, maximum SS (median and range) 27 (13-37) vs 55 (24-138) min, and maximum VSRS 51 (30-100) vs 80 (50-130) min. Children returned to normal activity in 1 (0-5) day, and none exhibited neurological complications. We conclude that an oral premedicant dose of midazolam prolongs recovery from anesthesia in children without affecting dystonic movements after propofol.

Background The rapid recovery from mivacurium- induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit. Methods In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg x kg(-1) edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode. Results Children arrived in the postanesthesia care unit 8.2 +/- 3-4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/- 0.05 vs. 0.93 +/- 0.01, P0.7 in all children. Adults arrived in the postanesthesia care unit 12.9 +/- 5.3 min after reversal of neuromuscular block(P Conclusions This study demonstrated that, in adults, failure to reverse mivacurium neuromuscular block was associated with an increased incidence of residual block. Such weakness was not observed in children receiving similar anesthetic and neuromuscular blocking regimens.

Currently, most elective pediatric surgery is performed on an out-patient basis. The objective of this case-control study was to identify potential determinants of patient cancellation at a children's hospital. Cases were defined as patients that were canceled on the day of surgery, whereas controls were those patients who underwent surgery on the scheduled date. Demographic and clinical data were collected using chart review. Approximately 10% of all day surgery patients were canceled on the day scheduled for surgery, half for reasons deemed preventable. Of the preventable cancellations, stepwise logistic regression analysis showed that patients attending only the surgeon's office prior to day surgery, were more likely to be canceled because of inadequate preparation, compared to those patients attending both the surgeon's office and the hospital preoperative clinic (adjusted odds ratio = 3.18; 95% CI: 1.32, 7.63).

BACKGROUND--Sepiolite is an absorbent clay that is used as pet litter. It forms thin crystals, which are a transition between chain and layered silicates. Inhalation studies in animals have shown no evidence of pulmonary damage. This paper reports a cross sectional study of the total work force of the largest sepiolite production plant in the world. METHODS--Two hundred and eighteen workers (210 men and eight women) were studied. Height, age, and smoking history were recorded. Chest radiographs were read according to the International Labour Office (ILO) classification by two readers. Readings were used to construct a numerical score, which was then used in statistical analyses. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were divided by the square of the height. Casella size selective personal samplers were used in randomly selected operatives to collect dust eight years before the rest of the study was carried out. These samples were evaluated gravimetrically. Total dust samples were examined by optical and electron microscopes. Results were analysed by bivariate linear regression, chi 2 tests, and analysis of variance. RESULTS--When allowance was made for smoking habit workers exposed to dry dust showed a significantly greater decline in FEV1 with age than workers with little exposure to dry dust. A similar pattern applied to FVC. Radiographic score showed deterioration with age but no clear differences from other variables. High concentrations of dust were found in the bagging department and also in the classifier shed. CONCLUSIONS--The major finding was that lung function deteriorated more rapidly in those who had had more exposure to dust, but there was no evidence of any accompanying radiographic change.

formed, written consent for inclusion in randomized controlled clinical trials, the use of their medical re cords in case reports/series, or for quality assurance and medical audit studies. In 2001, a review of 1,189 publications in six lead ing anesthesia journals found documented ethics com mittee approval in 71%, and individual written consent in 66% of the articles. rates varied among the journals with the highest rates (94% and 87%) for prospective clinical trials, and the lowest (2% and 3%) for case reports/series. Observational studies, prospective and retrospective, ranked in between. 1 Shortly after these results were published, most countries introduced leg islation to protect the privacy of individuals and pre

We have studied the effect of prior administration of non-depolarizing neuromuscular blocking drugs on suxamethonium-induced increases in masseter muscle tension in 21 children aged 3-10 yr, anaesthetized with nitrous oxide and halothane using supramaximal stimulation of the ulnar nerve and the nerve to masseter. Resting tension and isometric force of contraction were measured in the adductor pollicis and masseter muscles. A sub-paralysing dose of tubocurarine 0.05 mg kg-1, a paralysing dose of atracurium 0.5 mg kg-1 or saline was given, followed 3 min later by suxamethonium 1 mg kg-1. Onset times of suxamethonium and atracurium block were shorter in the masseter than in the adductor pollicis muscle. When preceded by a sub-paralysing dose of tubocurarine, suxamethonium produced an increase in masseter tension (47 (SEM 15) g) similar to that produced by suxamethonium alone (59 (13) g). Prior administration of a paralysing dose of atracurium almost abolished this increase in tension (2.5 (2.5) g) (P less than 0.05 vs saline). The tension increase in adductor pollicis was 0, 3.2 (2.2) and 5.9 (1.1) g in the atracurium, tubocurarine and saline groups, respectively. Tubocurarine and atracurium prevented muscle fasciculations in all patients. It was concluded that increased muscle tone is a normal response to suxamethonium and is greater in the masseter than adductor pollicis. Sub-paralysing doses of non-depolarizing neuromuscular blockers have little effect, in contrast with paralysing doses. This suggests that the effect is mediated via postsynaptic receptors.

Purpose of review This review will examine research ethics in the context of globalization of clinical trials and recent rapid developments in bioscience. It will focus on international ethical guidelines and the functions of research ethics review boards in research governance. Consent issues in genetic research, which must comply with privacy laws by protecting confidentiality and privacy of personal health data, will be discussed. Recent findings There has been a rapid expansion of genomic and proteonomic research and biotechnology in the last decade. International ethical guidelines have been updated and the bioscience industry has developed ethics policies. At the same time, problems in academic anesthesia in the US and UK have been identified, leading to recommendations to train physician-scientists in anesthesia to stimulate research activity in the future. Anesthesiologists are joining interdisciplinary research teams and the concept of evidence-based translational research is emerging. Summary Anesthesiologists are moving towards participation in interdisciplinary research teams. They are well placed to speed the translation of research discovery into clinical practice and provide evidence-based perioperative care. This review provides the ethical framework that anesthesiologists will need to meet the challenges of this changing pattern of practice.

The destabilization of endothelial nitric-oxide synthase (eNOS) mRNA in hypoxic endothelial cells may be important in the etiology of vascular diseases, such as pulmonary hypertension. Recently, an overlapping antisense transcript to eNOS/NOS3 was implicated in the post-transcriptional regulation of eNOS. We demonstrate here that expression of sONE, also known as eNOS antisense (NOS3AS) or autophagy 9-like 2 (APG9L2), is robustly induced by hypoxia or functional deficiency of von Hippel-Lindau protein. sONE is also up-regulated in the aortas of hypoxic rats. In hypoxic endothelial cells, sONE expression negatively correlates with eNOS expression. Blocking the hypoxic induction of sONE by RNA interference attenuates the fall in both eNOS RNA and protein. We provide evidence that the induction of sONE primarily involves transcript stabilization rather than increased transcriptional activity and is von Hippel-Lindaubut not hypoxia-inducible factor 2alpha-dependent. We also demonstrate that sONE transcripts are enriched in the nucleus of normoxic cells and that hypoxia promotes an increase in the level of cytoplasmic and polyribosome-associated, sONE mRNA. The finding that eNOS expression can be regulated by an overlapping cis-antisense transcript in a stimulus-dependent fashion provides evidence that sense/antisense interactions may play a previously unappreciated role in vascular disease pathogenesis.

Biomedical journals communicate new information that changes health-care decisions. If authors ignore the fundamental values of honesty and trust, that information becomes flawed, and society or patients may be harmed.By describing two cases of unethical behaviour by authors, and using them as a focus to review acceptable ethics in publication, this article aims to educate readers who have not considered the ethical implications in writing manuscripts for biomedical journals.Two cases of unethical behaviour by authors occurred when the results of new drug trials were reported. They were discovered after publication in a biomedical journal, and in the review process after the submission of a manuscript for publication respectively. In the first case, duplicate publication was identified because the same control data were used, but not acknowledged, in three publications by the same investigators. In the second, ghost writing by a pharmaceutical company writer was suspected because of the atypical presentation of a senior author's work.The editor consulted with the authors of both reports. In the first case, the authors concurred about the duplication, and the editors of the three journals wrote editorials to record the duplicate publications. The second case of ghost writing was unconfirmed by the authors, but the submission was withdrawn, and the article was later published in another journal.These cases draw attention to recently recognized types of scientific misconduct that influence the perception of scientific work. Duplicate publication and ghost writing not only deceive the reader, but may also conceal flawed study design and conflict of interest.

Clonidine is used for analgesia and sedation in paediatric anaesthesia, but there are no data on its sedative properties and side effects in critically ill children. We studied 30 ventilated children aged 10 yr and under to determine an effective i.v. dosing range and to assess its cardiovascular effects. Twenty non-paralysed, ventilated children were given a background infusion of midazolam 50 micrograms kg-1 h-1 combined with a variable clonidine infusion (0.1-2 micrograms kg-1 h-1) to maintain optimal sedation. The effects of clonidine 1 microgram kg-1 h-1 on cardiac index were measured in 10 postoperative cardiac patients using a reverse Fick method. Dose-dependent sedation was achievable (713 out of 861 h) without cardiovascular side effects, but an infusion limit of clonidine 1 microgram kg-1 h-1 was inadequate in two patients. An increased dose limit of 2 micrograms kg-1 h-1 combined with midazolam 50 micrograms kg-1 h-1 achieved satisfactory sedation scores for 602 out of a total of 672 h studied with no failures. Clonidine in combination with midazolam at 1 microgram kg-1 h-1 was not associated with significant changes in heart rate arterial pressure or cardiac index.

Double-burst stimulation (DBS), a new technique to evaluate neuromuscular function, consists of two 50-Hz trains of 60-ms duration and 750 ms apart. DBS was compared with train-of-four (TOF) stimulation in 21 children aged 3-10 yr, during halothane anesthesia. On one arm the ulnar nerve was stimulated supramaximally with TOF stimulation every 12 s and the force of the evoked contraction of the adductor pollicis measured with an FTO3 force transducer and recorded on paper. Atracurium (0.4-0.5 mg.kg-1) was administered. During recovery from neuromuscular blockade, TOF stimulation was interrupted periodically and DBS substituted. The same stimulation patterns were applied to the ulnar nerve of the other arm simultaneously, and the clinical anesthesiologist was asked to estimate the degree of fade with both. There was good correlation between the measured TOF ratio (ratio of fourth to first response) and DBS ratio (ratio of second to first response). The TOF and DBS ratios above which fade could no longer be appreciated manually were (mean +/- SEM) 0.44 +/- 0.03 and 0.67 +/- 0.04 (P = 0.0002). Corresponding ranges were 0.3-0.8 for TOF and 0.4-0.9 for DBS, but DBS fade was always apparent if TOF fade could be detected. Therefore, in children, DBS is more sensitive than is TOF stimulation for the clinical assessment of recovery from neuromuscular blockade.

The purpose of this review is to re-evaluate our approach to the perioperative management of children with congenital syndromes, as a result of recent advances in the understanding of the role of genetic factors in the aetiology of specific syndrome complexes, and in accordance with current paediatric anaesthetic practice. Recent information elucidating the genetic basis of these syndromes will be examined and made relevant to paediatric anaesthetists in their emerging roles as perioperative physicians. Diagnostic testing and family counseling, as well as alterations in reactions to drugs will be considered. Finally, the current year of clinical practice at this hospital will be reviewed to determine the frequency that congenital syndromes are encountered, the most common clinical challenges they present, and to provide examples of the management of anaesthesia in selected cases. The review aims to facilitate the anaesthetist's preoperative assessment of a child with a congenital syndrome, suggest approaches to clinical anaesthetic management, and be a basis for further study of the influence of genetics in anaesthesia.

Residual neuromuscular blockade is a major risk factor for respiratory insufficiency. We examined the relationship between neuromuscular and respiratory function in 18 ASA I or II children aged 2-4 years. Lung function was measured by pneumotachography and transpulmonary pressure, neuromuscular transmission by first twitch response ratio (T1:T1) and train-of-four ratio (TOFR), before and at specific points in recovery from vecuronium paralysis. The tidal volume was directly related to maximal inspiratory pressure at occlusion (P I OCC), P

To determine whether detection of residual blockade is improved by using the accelerograph. A secondary objective was to compare acceleromyographic measurements with those obtained by electromyography.In a prospective, randomized, double-blind investigation, 22 anaesthetized children were studied during recovery from neuromuscular blockade following 0.1 mg.kg-1 vecuronium i.v.. Assessments of depth of block began 10 min after injection and were repeated at one minute intervals using electromyography (Datex, Relaxograph) in one hand, and acceleromyography (Biometer, Tofguard) in the other, to measure response of the adductor pollicis to train-of-four (TOF) stimulation of the ulnar nerve. Monitoring was stopped when no fade was visible and TOF ratioor = 0.7. The electromyographic (EMG) and acceleromyographic (AMG) data were compared with corresponding observations of the number of twitches and TOF fade in the visible responses of the thumb, made by the attending anaesthetist. The method of Bland and Altman was used to compare differences between AMG and EMG data.During recovery from neuromuscular blockade, fade was no longer visible clinically 38.6 +/- 10.4 min (mean +/- SD) after the administration of vecuronium. This corresponded to TOF ratios of 0.04 +/- 0.23 by AMG and 0.34 +/- 0.21 by EMG. Usually, two twitches were visible before AMG detected the first twitch. The time to TOF ratioor = 0.7 by AMG and EMG was similar at 49.1 +/- 10.5 and 50.9 +/- 9.0 min, respectively. The bias between AMG and EMG was one minute, with limits of agreement from -10 to nine min.AMG is superior to visual assessment in detecting residual neuromuscular block and provides similar estimates of recovering block as the more cumbersome EMG.

A B-cell non-Hodgkin's lymphoma (B-NHL) cell line (Karpas 1106) with an unusual three-way translocation involving 18q21.3 has been derived from a patient with mediastinal lymphoblastic B-NHL. Although conventional cytogenetics showed a derivative 18q-identical to that seen in cases with t(14;18)(q32.3;q21.3), no translocations of either chromosome 14 could be detected. Instead fluorescent in situ hybridization analysis using a chromosome-18 paint showed that the segment 18q21.3-18qter had become sandwiched on a derivative chromosome X between segments Xqter-c-Xq28 and 13q12-qter, with the centrometric site of 18q21.3 subband juxtaposed to the X sequences. Pulsed-field DNA blots failed to detect rearrangement of the BCL2 gene. Conventional DNA blots using a variety of restriction digests and both 5' and 3' BCL2 and FVT 1 probes also failed to detect rearrangement in Karpas 1106. A rearranged fragment seen only in HindIII digests with 5' BLC2 probes may represent a local microalteration, which is either a mutation or small deletion involving the HindIII site as seen in other cases of B-NHL. Neither BCL2 RNA nor BCL2 protein expression were detected. These and other data suggest that genes at 18q21.3, other than BCL2 and FVT1, may be targets for translocation in certain subgroups of B-NHL.

Recovery after doxacurium and pancuronium neuromuscular blockade and their acceleration by neostigmine have not been compared in children. Therefore, 60 paediatric surgical patients aged 2–10 yr (ASA 1–2) were studied. They were randomized to receive doxacurium 30 μg · kg−1 or pancuronium 70 μg · kg−1 iv during propofol, fentanyl, isoflurane and nitrous oxide anaesthesia. Electromyographic (EMG) responses of the adductor pollicis to train-of-four (TOF) stimulation of the ulnar nerve were recorded every ten seconds using a Datex NMT monitor. Six patients in each relaxant group received neostigmine (0, 5, 10, 20 or 40 μg · kg−1) with atropine by random allocation when first twitch height (TI) had recovered to 25% of control. Spontaneous recovery after ten minutes was similar following doxacurium (mean ± SEM values of 45.0 ± 3.9 vs 49.5 ± 10.0 % for TI and 25.2 ± 3.8 vs 14.8 ± 3.6% for TOF ratios). Dose-responses to neostigmine were calculated from the log dose vs logit of TI or TOF ratio after ten minutes. Neostigmine-assisted recovery was not different in the two groups, with ED70 and ED90 doses for TI of 14.3 ± 1.8 and 25.7 ± 2.7 μg·kg−1 for doxacurium and 12.5 ± 1.7 and 25.3 ± 2.3 μg· kg−1 for pancuronium. Time to recovery of TOF ratio to 70% after neostigmine 40 ng · kg−1 was 2.3 ± 1.0 and 4.2 ± 1.7 min (P = NS) following pancuronium and doxacurium, respectively. Adjusted recovery due to neostigmine alone (spontaneous recovery subtracted from the total) required two to three times higher doses of neostigmine. Thus, in children, the spontaneous recovery and reversal of neuromuscular blockade is similar with doxacurium and pancuronium. However, compared with previous adult studies, they recover twice as quickly from doxacurium neuromuscular blockade and neostigmine antagonism is achieved at 25–50% of the adult doses.

Propofol anaesthesia may reduce postoperative emesis. The purpose of this study was to compare the incidence of emesis after propofol anaesthesia with and without nitrous oxide, compared with thiopentone and halothane anaesthesia, in hospital and up to 24 hr postoperatively, in outpatient paediatric patients after strabismus surgery. Seventy-five ASA class I or II, unpremedicated patients, aged 2-12 yr were randomly assigned to one of three groups: Thiopentone, 6.0 mg.kg-1 i.v. induction followed by halothane and N2O/O2 for maintenance (T/H); propofol for induction, followed by propofol and oxygen for maintenance (P/O2); and propofol for i.v. induction, followed by propofol infusion and N2O/O2 for maintenance (P/N2O). All received vecuronium, controlled ventilation, and acetaminophen pr. Morphine was given as needed for postoperative analgesia. There were no differences in age, weight, number of eye muscles operated upon, duration of anaesthesia or surgery. The P/N2O group (255 +/- 80 micrograms.kg-1 x min-1) received less propofol than the P/O2 group (344 +/- 60 micrograms.kg-1 x min-1) (P < or = 0.0001) and had shorter extubation (P < 0.001) and recovery (P < 0.01) times. Emesis in the hospital, in both the P/N2O (4.0%) and P/O2 group (4.0%) was less than in the T/H group (32%) (P < 0.01). Antiemetics were required in four patients in the T/H group (16.0%). Overall emesis after surgery was not different among the groups: T/H (48%), P/O2 (28%) and P/N2O (42%). The use of propofol anaesthesia with and without N2O decreased only early emesis. This supports the concept of a short-acting, specific antiemetic effect of propofol.

BACKGROUND Increasing age appears to be associated with a slower onset of neuromuscular blockade, but such an effect has not been studied with the same doses of the same drugs across pediatric and adult age groups. METHODS The authors measured the evoked compound action potential of the adductor pollicis muscle in response to 0.1-Hz stimulation of the ulnar nerve, during fentanyl-thiopental-oxygen anesthesia, in 160 patients aged 1-3 yr, 3-10 yr, 20-40 yr, or 60-80 yr. Subparalyzing doses of vecuronium (0.03 mg/kg) or succinylcholine (0.3 mg/kg), or paralyzing doses of vecuronium (0.1 mg/kg) or succinylcholine (1.0 mg/kg), were administered to ten patients in each age group. RESULTS Onset time, defined as the time from injection to maximum depression of response with a subparalyzing dose or the time from injection to ablation of visible response with a paralyzing dose, varied with age in all groups (P < 0.001). For 0.3 mg/kg succinylcholine, it increased from 49 +/- 6 s in 1-3-yr-old patients, to 104 +/- 9 s in 60-80-yr-old patients (P < 0.00001). For 0.03 mg/kg vecuronium, onset time was 3.6-5.9 times longer than for succinylcholine, increasing from 219 +/- 15 s in 3-10-yr-old patients to 473 +/- 30 s in 60-80-yr-old patients (P < 0.00001 by linear regression). For paralyzing doses, succinylcholine 1.0 mg/kg had an onset time of 58 +/- 7 s and 95 +/- 7 s, in 1-3-yr-old and 60-80-yr-old patients, respectively (P < 0.001). For 0.1 mg/kg vecuronium, onset time varied between 125 +/- 19 s in 1-3-yr-old patients to 295 +/- 31 s in 60-80-yr-old patients (P < 0.00001), and was 2.1-3.3 times longer than 1 mg/kg succinylcholine. CONCLUSIONS Increasing age is associated with slower onset for both succinylcholine and vecuronium. When equipotent, subparalyzing doses of succinylcholine and vecuronium are compared, onset time is 4.5 times as long with vecuronium.

Difficulties with disinfection of endoscopes and reports of cross-contamination of bronchoscopy specimens have previously been described. A recent episode of mycobacterial cross-contamination of bronchoscopy specimens was identified in a tertiary care referral centre. Two of eight bronchoscope suction valves cultured positive for Mycobacterium tuberculosis and the cause of the outbreak was traced to a faulty wash/disinfect switch in an automatic washer. The situation was resolved following autoclaving of all suction valves and repair of the endoscope washer. This report highlights the problems with instrument design and supports previous recommendations to autoclave suction valves routinely after each use.

Parental presence at induction of anaesthesia is desirable if it makes the child happier and more cooperative. This study evaluated the emotional and behavioural responses of children to being accompanied by a parent at induction of anaesthesia in a paediatric day-care surgical centre. One hundred and thirty-four patients (aged 2–10 yr, ASA physical status I or II) were divided into two groups by day of surgery, to have a parent present at induction of anaesthesia (treatment group), or to be unaccompanied (control group). Before, and at one week after surgery, the child’s fears and behaviour were scored by the Hospital Fears Inventory (HFI) and Behavioural Questionnaire (BQ), and parental anxiety by the Parents’ Questionnaire (PQ) before and at one week after surgery. The Global Mood Scale (GMS) was used to assess the child’s behaviour and the Visual Analogue Scale (VAS) to assess the parent’s anxiety on arrival for surgery and at induction of anaesthesia. All patients and parents were disturbed by the experience, but to the same degree in the treatment and control groups. Subgroups of “ calm ” and “ anxious ” parents were identified by a median split of their preoperative VAS scores. Children in the“ calm-treatment,” “ calm-control ” and“ anxious-control ” subgroups were similarly upset at induction. Children in the“ anxious-treatment ” subgroup were the most disturbed at induction, and significantly more than those in the“ anxious-control” subgroup. Preoperative parental anxiety levels also correlated with the child’s fears and behaviour one week after surgery. Therefore, parental anxiety should be assessed preoperatively to allow“calm” parents to be present at induction if they wish, and“anxious” parents to be excluded and receive counselling and support.

Background Reversal of neuromuscular blockade induced with pancuronium, d-tubocurarine, or doxacurium is achieved using smaller doses of neostigmine in adults than in children. Also, pancuronium- and doxacurium-induced blockade is reversed with smaller doses of edrophonium in children than in adults. The purpose of this study was to compare the spontaneous and neostigmine- and edrophonium-assisted recovery of mivacurium-induced neuromuscular block in adults and children. Methods Fifty-four adults, aged 40.1 +/- 10.9 yr, and 54 children, aged 4.9 +/- 0.7 yr, physical status ASA 1-2, were studied during propofol/fentanyl/nitrous oxide anesthesia. A Datex relaxograph was used to monitor the electromyographic response of the adductor pollicis to train-of-four stimulation of the ulnar nerve every 10 s. After induction of anesthesia, 0.2 mg x kg(-1) intravenous mivacurium was administered followed by an infusion to maintain 90-95% T1 block. At the end of surgery, one of four doses of neostigmine (5, 10, 20, and 50 micrograms x kg(-1)) or edrophonium (100, 200, 400, and 1,000 micrograms x kg(-1)) or placebo was given, by random allocation, when T1 had recovered to 10%. Values of T1 and train-of-four were measured for 10 min. Results Spontaneous recovery proceeded more rapidly in children than in adults. At 10 min, T1 had recovered to 97 +/- 2% (SD) in children compared with 69 +/- 11% in adults and train-of-four to 84 +/- 5% versus 30 +/- 13% (P Conclusions Spontaneous recovery from mivacurium- induced neuromuscular block is more rapid in children than in adults. Ten minutes after attempted reversal, recovery is accelerated by edrophonium and usually by neostigmine in adults but not in children. Thus, when reversal is required, edrophonium may be preferred to neostigmine.

This case report describes the anesthetic management of a 13-mo-old boy with mitochondrial myopathy requiring general anesthetic for diagnostic biopsy

After anesthesia employing nondepolarizing muscle relaxants, 30%-40% of adult patients demonstrate residual paralysis with a train-of-four ratio less than 70%, but it is not known if the same is true for children. This study was designed to investigate neuromuscular transmission in 91 ASA physical status I or II day-care children (aged 0-10 yr) after halothane anesthesia in which pancuronium (n = 34), atracurium (n = 32), or vecuronium (n = 25) was administered. Peripheral nerve stimulation was used clinically to assess neuromuscular blockade during surgery. In the recovery room, the evoked response of the adductor pollicis muscle was measured by train-of-four stimulation of the ulnar nerve. This measurement was made (mean +/- SEM) at 18.0 +/- 1.5, 15.0 +/- 1.3, and 15.0 +/- 1.7 min after pharmacologic antagonism with 0.02 mg/kg atropine and 0.06 mg/kg neostigmine in the pancuronium, atracurium, and vecuronium groups, respectively. There were no differences in the ages of the patients in the three groups at 4.3 +/- 0.4, 4.0 +/- 0.4, and 5.0 +/- 0.5 yr, with 17 children less than 2 yr. Recovery from neuromuscular blockade in all three groups was almost complete. The train-of-four ratio (height of fourth twitch compared with the first) was similar in patients who had received pancuronium (96.7% +/- 0.9%), atracurium (95.5% +/- 0.9%), or vecuronium (96.3% +/- 1.3%). Therefore, postoperative muscle weakness or respiratory impairment is unlikely in pediatric day-care surgical patients more than 2 yr old when these anesthetic techniques are used.

Bronchial hyper-responsiveness is a particular feature of asthma, but also occurs in normal subjects after a viral upper respiratory tract infection or ozone inhalation. Such stimuli would be expected to result in the release of chemical mediators of inflammation. In this study, the effects of one of these, prostaglandin F2 alpha (PGF2 alpha), on the response of normal subjects to inhaled histamine has been investigated. Nine normal volunteers took 10 inhalations of increasing concentrations of PGF2 alpha at 15-minute intervals from a Wright's nebuliser under standard conditions until a change in sGaw could be detected. The next lowest serial dilution of PGF2 alpha was subsequently inhaled by each subject every 15 min for 90 min to ensure the absence of a cumulative effect. Inhalation dose-response curves to histamine diphosphate were constructed on two separate occasions using the same standardised technique. Doses were administered every 15 min and sGaw determined five minutes after each. On one occasion each dose of histamine was immediately preceded by the non-active test dose of PGF2 alpha and on the second by saline as placebo. The study was performed double-blind and in random order. After pretreatment with PGF2 alpha the histamine dose-response curve was significantly shifted to the left in a parallel fashion (p less than 0.001). There was a significant decrease in the doses of histamine required to cause a 20% fall in sGaw (p less than 0.0015) but no significant change in the slopes of the dose-response regression lines, indicating that bronchial muscle sensitivity rather than reactivity had been predominantly affected.

A case report of a patient with Von Gierke's (glycogen storage disease Cori type (1)1 disease who required femoral osteotomy is presented. Current techniques of management of this condition which are likely to improve the outcome of general anaesthesia and surgery are discussed.

The role of histamine H1 and H2 receptors in the lung is not clear. H1 receptor blockade results in bronchodilatation and inhibition of histamine induced bronchoconstriction. H2 receptor blockade in vitro prevents the normal negative feedback of histamine on further mediator release in antigen challenge. Bronchospasm in guinea pigs given antigen challenge is enhanced by previous administration of metiamide or burimamide but not of cimetidine. These findings suggest the possible deleterious effect of H2 receptor antagonists in asthmatic subjects. The effects of H2 receptor blockade with cimetidine on bronchial hyperreactivity to histamine were studied in 10 asthmatic volunteers by whole body plethysmography. Cimetidine 800 mg and placebo were administered orally on two separate days, eight hours and two hours before study. No significant difference in baseline levels of airways obstruction was seen with the two agents. Inhalational challenge with increasing concentrations of histamine revealed no significant difference in bronchial hyperreactivity to histamine between cimetidine and placebo treatment days. H2 receptor blockade with cimetidine does not appear to affect ventilatory function or bronchial hyperreactivity to histamine in asthmatic subjects. It has been suggested that cimetidine may have H1 as well as H2 receptor blocking properties which prevent this effect.

A simple instrument for measuring adductor pollicis tension in children has been devised. The thumb sensor utilizes a thin conical rubber seal obtained from a 5, 10 or 20 ml Becton Dickinson syringe. A syringe barrel of similar size, fixed at right angles to the sensor, forms a handle for the fist. The sensor is linked to a pressure transducer with non-compliant tubing. Pressure output of the saline-filled system was found to be linearly related to the force exerted on each size of the sensor. In 20 children, aged two to eight years, the device, fitted in turn with the 5, 10 and 20 ml syringe seal sensors, gave train-of-four (TOF) ratios which showed close correlation (coefficient r = 0.96, 0.93, 0.95) and agreement (regression slope b = 0.97, 0.95, 0.98) with those of a force transducer. Thus, inspection of the displayed TOF pressure pulses gives a rapid and reliable estimate of neuromuscular blockade.

The effect of age on the onset and duration of action of a d-tubocurarine (DTC) neuromuscular blockade with and without pancuronium priming in children was examined. Sixty ASA physical status I or II patients in three age ranges (0-1 yr, 1-3 yr and 3-10 yr) were anaesthetized with thiopentone, halothane and nitrous oxide. Each patient received either a single paralyzing dose of DTC 0.4 mg.kg-1, or DTC 0.36 mg.kg-1 preceded three minutes earlier by pancuronium 0.007 mg.kg-1. Evoked force of contraction of the adductor pollicis was measured using train-of-four stimulation applied every 12 sec. Time to 90 per cent first twitch depression after a single dose of DTC increased with increasing age (r = 0.65, p less than 0.01), and was 1.6 min (SEM +/- 0.3) in the 0-1 yr group, 1.9 +/- 0.3 min (1-3 yr), and 5.2 +/- 1.2 min (3-10 yr). Time to ten per cent spontaneous recovery after single dose DTC was shorter in older individuals (r = 0.40, p less than 0.05), being 36.4 +/- 5.1 min in infants 0-1 yr, 30.6 +/- 4.6 min (1-3 yr), and 24.0 +/- 2.7 min (3-10 yr). Priming with pancuronium accelerated the onset significantly in all age groups with 90 per cent T1 depression occurring at 0.7 +/- 0.1 min (0-1 yr), 0.9 +/- 0.1 min (1-3 yr), and 2.1 +/- 0.6 min (3-10 yr). However, priming delayed recovery, especially in infants.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether airway receptors are responsible for the rapid, shallow breathing pattern seen in hypercapnic chronic obstructive lung disease, 10 patients underwent upper airway anaesthesia with inhaled lignocaine in a placebo controlled study. There was a significant reduction in breathing frequency after lignocaine (p less than 0.001) that was due to an increase in expiratory time (p less than 0.001). The inspiratory time remained unchanged, but tidal volume increased significantly (p less than 0.02). It is concluded that, while airway receptors may have a role in determining the frequency of breathing in chronic obstructive lung disease, other factors are responsible for the reduced inspiratory time.

A case of severe intravascular haemolysis, due to an ‘auto-anti-B antibody’, and a case of transient haemolytic anaemia, due to an ‘auto-anti-A antibody’, following allogeneic organ transplantation, are reported. Both patients were receiving immunosuppressive therapy with cyclosporin A and were non-secretors of A, B and H substances.

Twenty patients with haematological malignancies who developed Clostridium difficile bowel infection or colonisation are described. All isolates of C difficile were toxigenic in vitro and faecal cytotoxin (toxin B) was detected in 20/26 episodes. Ten of 20 episodes with detectable faecal cytotoxin were associated with typical antibiotic associated diarrhoea. In the other 10 episodes (nine patients), there was a severe unusual illness which was associated with detection of C difficile. The unusual features of the illness were pronounced jaundice (total bilirubin greater than or equal to 44 mumol/l), abdominal pain and distension, and initial constipation followed either by diarrhoea or by large bowel stasis. Four of these patients died within seven days. Bacteraemia was often a presenting feature in neutropenic patients subsequently shown to have C difficile. This was not the case in non-neutropenic patients. Bacteraemia was commonly polymicrobial and in two cases C difficile was isolated from blood culture. The clinical implications of recognition of this atypical C difficile associated syndrome are discussed.

A survey was undertaken among adults aged 20-44 years in a South Wales town. Persons with a history of wheezing with breathlessness and in the absence of a cold were identified by postal questionnaires and seen at a clinic, together with a sample of subjects without these symptoms. The response rates for the first and second stages of the survey were 99.6% and 91.0% respectively, and 574 subjects were ultimately seen. Asthmatic patients (those receiving treatment within the previous year) had some airways obstruction at rest, which increased after exercise. They also had strong allergic tendencies, as shown by personal and family history, skin tests, and serum IgE levels. The ex-asthmatics (those not receiving treatment within the previous year) showed these tendencies to a lesser extent. A larger group gave a history of wheezing but stated that they had never had asthma; in their response to exercise and allergic traits they resembled the control group rather than the asthmatics, and appeared to have the features of chronic bronchitis. Asthma and chronic bronchitis would therefore seem to be distinct entities within the population studied.

Karyotypes of bone marrow cells from 24 patients with multiple myeloma (MM) and two patients with de novo plasma cell leukaemia (PCL) were analysed by Giemsa banding (G banding). Chromosome aberrations were found in 13 patients with MM and both patients with PCL. Hyperdiploid and hypodiploid lines were present in eight and five of the patients with MM, respectively. Marker chromosomes derived from structural rearrangements were present in all eight cases of MM with hyperdiploid lines, although markers of uncertain origin were rare in those patients with hypodiploid lines. Chromosome 1 participated most often, and chromosomes 5 and 9 often played a part in the structural rearrangements. Chromosomes 3, 5, 7, 9, 11, 15, 19, and 21 were subject to numerical aberrations. In the two patients with PCL one had a hypodiploid line with a 14q + marker derived from a t(11;14) and the other a hyperdiploid line. The breakpoints on the chromosomes participating in the structural rearrangements in myeloma showed a good correlation with known fragile sites and oncogene locations on the corresponding chromosomes.

Characteristics of sickle ceil disease History Epidemiology and genetics Association with malaria Inheritance Clinical features Modifiers of clinical severity Pathophysiology Haemoglobinopathy Oxygen affinity Blood viscosity Cell membrane damage Micrncirculatory changes Molecular biology of sickle eelI anaemia Diagnosis Clinical examination Peripheral blood film and CBC Haemoglobin e]ectrophoresis I~rnergeney use of sodium metabisulphate preparation Neonatal diagnosis Prenatal diagnosis Treatment Supportive Specific therapies Augmentation of haemoglobin F Bone marrow transplantation Transfusion therapy Organization of Sickle Cell Centres in North America Management of general anaesthesia Preoperative considerations Technique of anaesthesia Sielde ceil crisis intraoperatively Controversies in anaesthetic management Preoperative use of blood transfusions The obstetric patient Neonates and infants The patient for open heart surgery

Seventeen patients with hairy-cell leukaemia (HCL) and peripheral cytopenias were given human lymphoblastoid interferon (Wellferon), 3 megaunits daily or 6 megaunits on alternate days intramuscularly, for 4-24 weeks. Twelve of the patients had undergone splenectomy, three had no palpable spleen and had therefore not been offered surgery, and two patients with substantial splenomegaly were given interferon (IFN) as treatment of first choice. Toxic effects were minor except in one patient who experienced a severe form of somnolence syndrome. In all patients hairy cells (HCs) were cleared from the blood and platelet and Hb levels improved in 2-14 weeks. Neutrophils were improved in 14/17 of the patients. In the two patients with splenomegaly, the spleen became impalpable after 5-8 weeks therapy, and haematological improvement occurred at 12-14 weeks. HC infiltration of the marrow was reduced in all patients, but was complete (less than 5%) in only two, both of whom had impalpable spleens. Immunological surface-marker studies confirmed that light-chain-restricted B cells disappeared from the blood in parallel with the clearance of morphological HCs. There was no evidence of HC maturation and no increase in phenotypic NK cells. T cells were moderately reduced and the relatively greater reduction of Leu 2a+ suppressor cells resulted in increased Leu 3a+/2a+ helper/suppressor ratios in 11/17 of the patients. Early experience in the six patients who have stopped IFN suggests that, after an initial further increase in Hb and neutrophil levels, HCs gradually return with slow deterioration of haematological parameters. Interferon is now the treatment of choice for patients becoming cytopenic post-splenectomy or for patients without splenomegaly. IFN is effective first-line therapy in patients with splenomegaly, but further work is needed to establish whether the agent should replace splenectomy in such patients. Some form of maintenance or re-treatment therapy will probably be necessary.

Arterial oxygen saturation was measured by pulse oximetry in two groups of paediatric outpatients breathing room air during transport from the operating room to the postanaesthetic recovery room. In Group I (n = 60) readiness for transfer from OR to PARR was decided clinically. In Group II (n = 50) additional criteria of oxygen saturation (SaOe) greater than or equal to 98 per cent with end-tidal gas N2O less than or equal to 10 per cent and CO2 less than or equal to 45 mmHg were met. A higher incidence of desaturation (SaO2 less than or equal to 90 per cent) occurred in Group I (27 per cent) than in Group II (eight per cent) (P less than 0.05). More children under 2 yr desaturated in Group I (50 per cent) than Group II (17 per cent) (P greater than 0.05 less than 0.10). Twenty-two patients in each group had a recent history of upper respiratory tract infections. In these patients, desaturation was more marked in those in Group I (32 per cent) than in Group II (five per cent) (P less than 0.05). Within each group, the incidence of desaturation during transport was similar in patients with or without a recent URI.

To measure the potency of pancuronium at the diaphragm and adductor pollicis in infants and children, train-of-four stimulation was applied to the ulnar and phrenic nerves under N2O-halothane anesthesia. The force of contraction of the adductor pollicis was measured and compared with the diaphragmatic electromyogram (EMG). Cumulative dose response curves were determined for pancuronium in 18 patients divided equally into three age groups: 0-1 yr, 1-3 yr, and 3-10 yr. The potency of pancuronium at both muscles decreased with increasing age (P less than 0.05), while the adductor pollicis:diaphragm potency ratio remained constant. The mean doses (+/- SEM) required to depress adductor pollicis first twitch responses by 90% (ED90) were 42 +/- 3.3 micrograms/kg in the 0-1-yr group, 47 +/- 4.2 micrograms/kg in the 1-3-yr group, and 62 +/- 4.1 micrograms/kg in the 3-10-yr group. Corresponding figures for the diaphragm were 70 +/- 4.3 micrograms/kg, 81 +/- 5.1 micrograms/kg, and 101 +/- 4.4 micrograms/kg, respectively. The ED90 ratios (diaphragm ED90/adductor pollicis ED90) in the three age groups were 1.69 +/- .07, 1.75 +/- .14, and 1.64 +/- .09, respectively. These results are consistent with similar rates of maturation of the diaphragm and the adductor pollicis muscles in infancy and childhood. Thus, train-of-four monitoring of the adductor pollicis is likely to overestimate the degree of neuromuscular blockade of the diaphragm in pediatric patients.

The study was designed to compare the frequency and severity of postoperative vomiting in paediatric out-patients receiving controlled ventilation (IPPV) or breathing spontaneously (SV) during anaesthesia for strabismus repair. One hundred and twenty unpremedicated children (ages 2-12 years) were studied in a randomized fashion. After intravenous induction of anaesthesia and tracheal intubation, patients breathed halothane 1-1.5 per cent inspired and N2O 66 per cent in O2 spontaneously (n = 60), or received IPPV, halothane 0.5-1 per cent, N2O 66 per cent, and pancuronium 0.05 mg.kg-1, which was reversed with neostigmine and atropine (n = 60). The incidence of vomiting with SV was 50 per cent (95 per cent confidence limits: 34.5-65.5 per cent) compared with 40 per cent (24.5-55.5 per cent) with IPPV (p greater than 0.25). Patients in the SV group experiencing emesis had longer operations than those not vomiting (mean +/- SEM = 1.5 +/- 0.1 vs 1.2 +/- 0.1 hours, p less than 0.005). This was not the case with IPPV. There was no correlation between age, sex, duration of surgery, or number of extraocular muscles repaired, and frequency or severity of vomiting or time to discharge. No significant advantage was afforded by IPPV over SV in the present study.

A case report is presented of a patient receiving chronic phenytoin therapy who demonstrated resistance to pancuronium by increased hourly requirements. Stable neuromuscular blockade was achieved by atracurium infusion at normal rates. Possible explanations for the differences in response to the two non-depolarizing muscle relaxants are discussed.

Studies were performed to investigate whether hyperresponsiveness of the airways could be induced in normal subjects by inhalation of prostaglandin E2 (PGE2). During the initial bronchodilator phase of PGE2 action the bronchoconstrictor effect of inhaled histamine was significantly antagonised. When bronchoconstrictor challenges were started shortly after the end of the bronchodilator response to PGE2, however, significant enhancement of the effects of both inhaled histamine and methacholine occurred. It was predominantly sensitivity to these agents that was increased, with a parallel shift of the dose-response curves towards increased bronchoconstriction. Thus PGE2 may be protective in the acute phase of a bronchoconstrictor challenge, but in a chronic inflammatory condition its net effect may be a balance between this beneficial action and a non-specific potentiation of the activity of bronchoconstrictor agents.

Nineteen stable asthmatic patients were given killed influenza virus intramuscularly. In 9 patients who developed a fourfold or greater rise in haemagglutination antibodies, an increase in airway sensitivity to histamine was demonstrated 48 h later. There was no significant change in histamine sensitivity in those patients who failed to develop a fourfold rise in haemagglutination antibodies. The increased histamine sensitivity was not associated with a deterioration in asthma symptoms, peak expiratory flow, nor an increase in bronchodilator requirements.