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Dynamic contrast-enhanced MR imaging (DCE-MRI) may act as a biomarker for successful cancer therapy. Simple, reproducible techniques may widen this application. This paper demonstrates a single slice imaging technique. The image acquisition is performed in less than 500 ms making it relatively insensitive to respiratory motion. Data from phantom studies and a reproducibility study in solid human tumours are presented. The reproducibility study showed a coefficient of variation (CoV) of 19.1% for K(trans) and 15.8% for the initial area under the contrast enhancement curve (IAUC). This was improved to 16 and 13.9% if tumours of diameter less than 3 cm were excluded. The individual repeatability (the range within which individual measurements are expected to fall) was 30.6% for K(trans) and 26.5% for IAUC for tumours greater than 3 cm diameter. This approach to DCE-MRI image acquisition can be performed with standard clinical scanners, and data analysis is straightforward. For treatment trials with 10 patients in a cohort, the CoV implies that the method would be sensitive to a treatment effect of greater than 18%. The individual repeatability is well inside the 40% change shown to be important in clinical studies using this DCE-MRI technique.

Simulator radiographs taken as a record of breast radiotherapy planning often show ill defined breast tissue margins because exposure parameters are set to optimize visualization of the chest wall rather than the bulk of the breast. This creates difficulties when using simulator images as reference images in verification by comparing with either portal film or images from an electronic portal imaging device. Our aim was to improve breast images taken at simulation without changing exposure parameters that have been optimized for visualization of the chest wall. This has been achieved via an external filter to be used when taking radiographs with the treatment simulator. The filter is made of stainless steel coated with tin and is shaped to maintain acceptable imaging of the chest wall by covering only the section of field anterior to the chest wall. Radiographs of breast simulations using the filter have been accepted as satisfactory by both clinicians and radiographers. The filter is now in routine clinical use for breast and chest wall treatment simulation.

Summary The use of the new competitive muscle relaxant, atracurium, is described in five myasthenic patients presenting for thymectomy. With an initial dose of 0.1 mg/kg, that is approximately one-fifth of that normally used, and incremental doses of 0.02–0.04 mg/kg, satisfactory clinical conditions were achieved. Neuromuscular function was monitored throughout using the train-of-four mechanical twitch response, and residual neuromuscular blockade was reversed satisfactorily at the end of the procedure with neo-stigmine 5.0 mg. A marked increase in the magnitude of the first twitch of the train-of-four to greater than control levels, accompanied by pronounced fade. was found on reversal. In reduced dosage and with careful neuromuscular monitoring, atracurium is safe to use in the myasthenic patient.

Hypocapnia was induced in dogs lightly anaesthetized with nitrous oxide and fentanyl. Measurements were made of estimated renal plasma flow (ERPF), glomerular filtration rate, vascular resistance and urine production. During the (short) duration of the experiments hypocapnia was found to be associated with ERPF twice that during normocapnia. Glomerular filtration rate and urine output were increased by hypocapnia in an approximately similar proportion, whilst renal vascular resistance halved. Though some of the experimental animals had a degree of metabolic acidosis this was thought not to have greatly influenced the results.

A comparison between the effects of increasing concentrations of enflurane and halothane on cardiovascular and renal function in the artificially ventilated dog showed that both agents produced myocardial depression which was directly related to the concentration administered. Depression was more marked, and occurred at a lower minimum alveolar concentration (MAC) value with enflurane. No significant difference was found between the effects of the two agents on renal blood flow, glomerular filtration rate, renal vascular resistance or urine production at anaesthetic concentrations of 1 MAC. However, there was evidence of sudden depression of renal function as concentrations of enflurane were raised above 1 MAC, but with halothane a similar deterioration did not appear until the concentration of the inhalational agent reached 2 MAC.

A hydroxypyruvate reductase has been induced in Pseudomonas acidovorans by growth on glyoxylate. The enzyme has been purified to homogeneity as assessed by the criteria of analytical ultracentrifugation and analytical disc gel electrophoresis. It has a molecular weight of approximately 85,000 and is composed of two identical subunits. The subunits are not interconnected by disulfide bonds although the enzyme has 4 mol of half-cystine per mol of enzyme. The enzyme catalyzes the reversible conversion of hydroxypyruvate to D(minus)-glycerate in the presence of NADH. Glyoxylate cannot replace hydroxypyruvate as a substrate and is a competitive inhibitor of hydroxypyruvate reduction. The activity of the enzyme toward hydroxypyruvate is anion-modulated; the activity of the enzyme toward D(minus)-glycerate is unaffected by anions but is increased by tris-(hydroxymethyl)aminomethane. The subunits of the induced hydroxypyruvate reductase can be renatured. After the enzyme is dissociated in solutions of 6.0 M guanidine hydrochloride containing 0.1 M 2-mercaptoethanol, optimum renaturation occurs when subunits are diluted into a renaturation solvent consisting of 0.04 M Trischloride, pH 7.4, containing 25% glycerol, 25 mM 2-mercaptoethanol, and 0.14 MM NADH. NAD is an inhibitor of renaturation and therefore cannot substitute for NADH. The optimal temperature of dilution and subsequent incubation is 15 degrees, and increases in protein concentration up to 1.2 mg/ml, the highest concentration tested, improve both the rate of renaturation and the yield of active material. The half-time of renaturation at a protein concentration of 1.2 mg/ml was 1 min. The kinetics of renaturation is second order, i.e., is compatible with a bimolecular reaction preducted by the association of two similar subunits. The physical and kinetic parameters of the renatured protein are the same as those of the native enzyme.

Summary The anaesthetic management of a patient suffering from carcinoid syndrome and myasthenia gravis is described including the successful treatment of a carcinoid attack with intravenous aprotonin. The differences between myasthenia gravis and the myasthenic (Eaton-Lambert) syndrome are considered and the rationale for the choice of vecuronium as the muscle relaxant is discussed.

The clinical neuromuscular effects of two doses of vecuronium (0.15 mg kg-1 and 0.2 mg kg-1) were investigated in 20 healthy patients and 20 patients with cirrhosis, and compared with previous work in which vecuronium 0.1 mg kg-1 was given under identical conditions of anaesthesia and monitoring. Ten healthy patients received vecuronium 0.15 mg kg-1 and 10 received 0.2 mg kg-1. Similarly, 10 patients with cirrhosis received vecuronium 0.15 mg kg-1 and 10 received 0.2 mg kg-1. Vecuronium 0.1 mg kg-1 has previously been shown to have a somewhat shorter duration of action in cirrhotic as opposed to healthy patients. In this study, vecuronium 0.15 mg kg-1 was found to have a similar duration of action in both groups, and vecuronium 0.2 mg kg-1 had a significantly longer action in the cirrhotic group. It is suggested that vecuronium should be used with caution in patients with hepatic dysfunction and that, in such patients, monitoring of neuromuscular function is desirable.

Atracurium is a new, non-depolarizing muscle relaxant which rapidly breaks down in vivo and appears to require neither renal nor hepatic function for its elimination. As the commonly used non-depolarizing muscle relaxants carry the risk of prolonged effect when used in anephric patients, atracurium appears to have special promise in this situation. A preliminary account of the successful use of the relaxant in 20 anephric patients is recorded and evidence presented that atracurium is, indeed, a suitable agent for use in patients with renal failure.

Vecuronium (initial dose 0.1 mg kg-1; incremental doses 0.04 mg kg-1) was given to 21 normal and 21 anephric patients. There were no gross differences between the two groups in the effect or in the duration of action of either initial or incremental doses, except in two anephric patients who were resistant to the agent. Reversal with neostigmine was satisfactory. In normal patients the initial dose of vecuronium was slower in onset of action than was atracurium 0.5 mg kg-1 (26 patients): the first two incremental doses of vecuronium were administered significantly earlier than the corresponding increments of atracurium (0.2 mg kg-1), but the duration of action of increments over-all was not greatly different. However, in anephric patients, except in the resistant patients, the behaviour of vecuronium was similar to that of atracurium (26 patients). A comparison with an initial dose of tubocurarine 0.5 mg kg-1 given to 20 anephric patients and tubocurarine 0.6 mg kg-1 given to 21 normal and 20 anephric patients showed tubocurarine to be longer acting and considerably less predictable. This was particularly so in the anephric group, in which its action sometimes persisted after neostigmine had been given.

An investigation is described into the performance of two types of circle system used without a carbon dioxide absorber in both the laboratory and in the operating theatre with controlled ventilation. The newer system was found to be more efficient than the old but in both types of system the tidal volume was found to be very important, a large tidal volume resulted in increased efficiency. The possibility of predicting arterial blood carbon dioxide using this system is briefly discussed, and rules are suggested for the use of the system.

Postoperative analgesia both by drugs and regional techniques is reviewed. In the United Kingdom in the last 25 years or more there has been little advance on either front. Some marginal improvement in regard to drugs might be brought about by better education of both doctors and nurses and better patient contact. Extradural analgesia and intercostal block do not offer a complete solution, though a judicious increase in the use certainly of the former might be beneficial. The problem awaits a radical new approach.

SUMMARY It is frequently held that patients with severe respiratory disability should not be subjected to anaesthesia involving the use of relaxant drugs and positive pressure ventilation since it may be found impossible to provide adequate pulmonary ventilation after the relaxant has been given, or it may prove difficult to re-start spontaneous ventilation if the blood carbon dioxide tension has been reduced during anaesthesia. This paper describes a simple investigation into this problem based on data obtained from 12 ‘respiratory cripples.’ All had a maximum breathing capacity of less than 40 litres/min., and eight showed pre-operative respiratory acidosis. Premedication was with promethazine and atropine. Anaesthesia was induced with a small dose of thiopentone; muscular relaxation was produced by a large dose of tubocurarine, endotracheal intubation effected without the use of topical analgesics, and anaesthesia maintained with a mixture of nitrous oxide and oxygen, without die use of depressant drugs or volatile agents. A deliberate attempt was made to produce passive pulmonary hyperventilation by manual pressure on the reservoir bag, and in every case it was found possible to reduce the blood carbon dioxide tension to below the level found pre-operatively and usually to below 40 mm Hg. In no case was it found difficult to ventilate the patient's lungs, and there was no evidence of progressive hyper-inflation. At the end of the operation, atropine and neostigmine were administered; it was found that after stimulation of the pharynx and trachea spontaneous respiration appeared with the endotracheal tube still in situ and the patient still unconscious when the blood carbon dioxide tension was still lower than it had been pre-operatively. After extubation, which was accompanied by some breath-holding and coughing, a regular pattern was soon re-established at a blood carbon dioxide tension strikingly similar to that which had been found before anaesthesia. It is suggested that these results would not have been obtained had depressant drugs or volatile anaesthetic agents been used, and that the application of topical analgesic solutions to the larynx may likewise cause difficulty in re-starting spontaneous respiration. The use of full muscular relaxation would also seem to be of importance in preventing progressive hyperinflation and difficulty in maintaining adequate ventilation. ZUSAMMENFASSUNG Vielfach wird die Ansicht vertreten, dass bei Patienten mit schweren respiratorischen Storungen die Anaesthesie ohne Relaxans und ohne positive Druckbeatmung durchgefuhrt werden solle; einmal konne es schwierig sein, eine ausreichende Ventilation der Lungen nach Verabreichung des Relaxans zu erzielen, zum anderen konne die Wiederkehr der Spontanatmung schwierig zu erreichen sein, wenn die Kohlensaurespannung wahrend der Narkose verringert wurde. Diese Arbeit beschreibt eine einfache Untersuchung dieser Frage an Hand der Ergebnisse an 12 “respiratorischen Kriippeln” (Atemgrenzwert unter 40 1/min, in 8 Fallen praeoperative respiratorische Acidose). Die Praemedikation bestand aus Promethazin und Atropin; Narkoseeinleitung mit einer kleinen Dosis Thiopental, Relaxation mit einer hohen Dosis Tubocurarin, Intubation ohne Lokalanaesthesie; weitere Narkosefuhrung mit N2O-O2 ohne Zusatz anderer Inhalationsanaesthetika oder depressiv wirksamer Medikamente. Es wurde passive, manuelle Hyperventilation angestrebt; stets gelang es, die Kohlensaurespannung des Blutes unter praeoperative Werte zu senken, meist sogar unter 40 mm Hg. Ventilationsschwierigkeiten oder Zeichen allmahlicher Uberblahung traten nicht auf. Zu Operationsende Gabe von Atropin und Neostigmin. Bei Stimulation von Pharynx und Trachea trat-am bewussdosen Patienten bei noch liegender Tube-wieder Spontanatmung auf, obwohl der Kohlensauredruck noch unter den praeoperativen Werten lag. Nach Extubation (meist unter Husten und Atemanhalten) kam es bald zu einer regelmassigen Spontanatmung bei Werten der Kohlensaurespannung, die fast genau den praeoperativen Befunden entsprachen. Die Autoren sind der Ansicht, dass bei Gebrauch von Analgetika und Inhalationsanaesthetika diese Ergebnisse nicht zu erzielen gewesen waren, Gleiches gilt hinsichtlich ordicher Betaubung des Larynx. Fur die Verhutung allmahlicher uberblahung und von Schwierigkeiten der Beatmung scheint die komplette Relaxierung von grosser Bedeutung.

An attempt is made to assess the importance of awareness and dreaming in patients subjected to light anaesthesia with muscle relaxants. Frank awareness is probably an uncommon event if the anaesthetic be given competently, but unpleasant dreams can, in some circumstances, be significant.

SUMMARY Changes from normocapnia to hypocapnia (and vice versa) were induced in dogs lightly anaesthetized with nitrous oxide and halothane and subjected to passive pulmonary ventilation. During hypocapnia estimated renal plasma flow and urine production were greater than in normocapnia, and renal vascular resistance was decreased greatly compared with normocapnia. There was little change in glomerular filtration rate.

The potentiation of alcuronium by halothane, enflurane and isoflurane was investigated using electromyography. In the first study, cumulative dose-response curves were constructed in four groups of 10 patients anaesthetized with one of the inhalation agents and nitrous oxide, or with fentanyl and droperidol (control). All three agents reduced the ED50 of alcuronium; the effect was marked with isoflurane (P less than 0.005) but less so with halothane (P less than 0.05) and enflurane (ns). In the second part of the investigation, designed primarily to test the duration of action of alcuronium with each agent, a single bolus dose of alcuronium 0.2 mg kg-1 was given to four similar groups (n = 5). The duration of action was significantly prolonged by enflurane (P less than 0.01) and isoflurane (P less than 0.05), but not by halothane. The possible reasons for this are discussed.

Summary The use of vecuronium in six patients with myasthenia gravis undergoing thymectomy is described; the train-of-four twitch technique was used to monitor neuromuscular function. The first two patients received an initial dose of 0.02 mg/kg and incremental doses of 4 μg/kg, which is in the order of one fifth of that normally used. Satisfactory depression of the first twitch of the train-of-four, however, was not obtained and, therefore, in the remaining four patients the doses were doubled. At this dose satisfactory depression of the first twitch was achieved. Neostigmine 5.0 mg produced adequate reversal of residual neuromuscular blockade and the train-of-four twitch response recovered to normal levels. With reduced dosage and with careful neuromuscular monitoring. vecuronium can be used safely in the myasthenic patient.

The drug, atracurium besylate is one of a new series of competitive muscle relaxants. Doses of 0.2, 0.4 and 0.6 mg/kg produced neuromuscular block in the anaesthetised dog with no cardiovascular effects. The neuromuscular block was readily reversible by neostigmine.

A survey of 100 consecutive patients suggests that, overall, ophthalmic surgery is not as painful postoperatively as general surgery. Cataracts are largely painless. Retinal detachments may sometimes give rise to postoperative pain like that in general surgery, but the numbers available are not yet sufficient for statistical analysis. Routine postoperative analgesia for encirclement procedures in retinal detachment patients should be considered for at least the first 18 hours after operation.

The effects of atracurium (initial dose 0.5 mg kg-1; incremental doses 0.2 mg kg-1) and vecuronium (initial dose 0.1 mg kg-1; incremental doses 0.04 mg kg-1) are described in patients with portal hypertension and some degree of liver dysfunction, and the findings compared with those from normal patients. With these doses there was no evidence of gross resistance to the two neuromuscular blockers in the patients with liver problems, although the duration of action of the initial dose was somewhat shorter, and the same may have been true of incremental doses. The method of elimination would suggest that atracurium may be the better drug in patients with severe liver dysfunction, but the use of small doses of vecuronium is not contraindicated in this type of patient.

A comparison between the effects of increasing concentrations of enflurane and halothane on cardiovascular and renal function in the artificially ventilated dog showed that both agents produced myocardial depression which was directly related to the concentration administered. Depression was more marked, and occurred at a lower minimum alveolar concentration (MAC) value with enflurane. No significant difference was found between the effects of the two agents on renal blood flow, glomerular filtration rate, renal vascular resistance or urine production at anaesthetic concentrations of 1 MAC. However, there was evidence of sudden depression of renal function as concentrations of enflurane were raised above 1 MAC, but with halothane a similar deterioration did not appear until the concentration of the inhalational agent reached 2 MAC.

An investigation is described into the performance of two types of circle system used without a carbon dioxide absorber in both the laboratory and in the operating theatre with controlled ventilation. The newer system was found to be more efficient than the old but in both types of system the tidal volume was found to be very important, a large tidal volume resulted in increased efficiency. The possibility of predicting arterial blood carbon dioxide using this system is briefly discussed, and rules are suggested for the use of the system.

One hundred general surgical patients were subjected to a form of personality assessment (Eysenck and Eysenck, 1964) the day before operation. Anaesthesia was standardized using light general anaesthesia, a muscle relaxant and controlled ventilation. The day after surgery patients filled in a standardized postoperative questionnaire about complaints concerning their visit to theatre. The patients were more “neurotic” (had higher N scores) than the general population; they also had a higher lie (L) score, and this tended to increase with age. The N score was greater in those awaiting upper abdominal operations than in those awaiting other procedures, and greater in females than in males. Pain was the most conspicuous postoperative complaint, despite the use of conventional analgesia. Preoperative anxiety was also prominent, as were complaints related to the passage or presence of a nasogastric tube. There was a positive correlation between N score and complaints of anxiety, and between N score and total number of complaints, but not between N score and complaints of pain.

SUMMARY Recent work has suggested that the term pK1′ in the Henderson-Hasselbalch equation may show wider variation than has been thought, and it seemed possible that the generally accepted values might not apply to women in labour. pK1′ was therefore determined experimentally in twenty volunteers in normal labour using arterialized venous blood. pH was measured by the glass electrode, Pco2 by the carbon dioxide electrode and Cco2 by the manometric apparatus of Van Slyke. The value so obtained was 6.106 at 38°C (with a standard deviation of 0.011). This was identical with the value obtained from ten non-pregnant controls and accords well with the value generally accepted as normal. This finding demonstrates the validity of the use of such nomograms as those of Siggaard-Andersen (1962a, 1963) and incidentally confirms the existence of a metabolic acidosis during labour.

An account is given of the 602 anaesthetic accidents reported to the Medical Defence Union of the United Kingdom over the eight-year period 1970-1977: these were reported from a total membership of 2,000 anaesthetists. It is known that reporting of minor accidents, for example damage to teeth, is very imcomplete, and that many deaths associated with surgery but due to disease processes rather than anaesthesia would not be reported either. It is thought, however, that the reporting by members of other accidents involving death and cerebral damage is likely to be complete, or nearly so. Cases of death and cerebral damage reported numbered 348 (60 per cent of the total) and the causes of these two major accidents were so closely similar that it was possible to deal with them together. This appears to be a suitable approach since cerebral damage can be as great, or greater, a catastrophe than death. In nearly half of this group of accidents there was discernibly faulty technique. Failure of postoperative care ( 10 per cent of the 348 cases) was another prominent and avoidable cause. Analysis of the faulty anaesthetic techniques which led to these major accidents showed that factors involved in tracheal intubation were preeminent, and that misuse of apparatus was also conspicuous. Over all error was deemed to be twice as common a cause of death and cerebral damage as was misadventure.

The effect of halothane on experimental ischaemic muscle pain has been studied in 18 human volunteers. The submaximum effort tourniquet test was used in this investigation because it has been shown by previous workers to be a sensitive experimental test of analgesia. Two concentrations of halothane (0.25 and 0.35%) were compared with nitrous oxide (30%) in a controlled experiment. It was found that halothane 0.35% is of the same order of effectiveness as an analgesic as is nitrous oxide 30%. Halothane 025% appeared to have no analgesic action, and the possibility of a slight antanalgesic action at this concentration could not be eliminated. The practical effects of this finding are reviewed, and it is suggested that this finding taken with the work of other investigators indicates that halothane should be considered as an analgesic drug, and that the application of the term antanalgesic to this agent is misleading.