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A case-controlled study of the cerebral ultrasound appearances of neonates following placental abruption was undertaken. Twenty-nine index subjects (median gestation 29 weeks) were identified over a 2-year period with gestation- and sex-matched controls. Placental abruption was associated with a four-fold increased incidence of periventricular leukomalacia and extensive periventricular haemorrhage, without increased mortality. Ten infants (34%) developed cystic periventricular leukomalacia following placental abruption, compared with three (10%) in the control group. Intraventricular haemorrhage (excluding subependymal haemorrhage) and haemorrhage into the brain parenchyma occurred in 21 (72%) infants in the abruption group, compared with 14 (48%) in the control group (P < 0.05).

The influences of GaI3, InI, and TlI on the evaporation characteristics of CeI3 have been studied over the temperature range 900 K to 1400 K using x-ray induced fluorescence. The total vapor densities, summed over all atomic and molecular species, of Ce, I, In, and Tl were obtained. Measurements of Ce were limited to temperatures above 1033 K, the melting temperature of CeI3. This is the highest temperature range for which measurements of the vapor pressure of CeI3 have been made. The vapor pressure of the CeI3 monomer above the pure CeI3 salt for temperatures exceeding its melting point can be approximated by log10p/Pa=11.24(±0.03)−10,690(±40) (T/K)−1 where the numbers in parentheses are standard uncertainties. InI and TlI were shown to modestly enhance the presence of Ce in the vapor phase, up to a factor of 5. GaI3 produced no enhancement in this temperature range. Numerical simulations of the thermochemical equilibrium suggest the importance of both liquid-phase and vapor-phase complexes. Significant ...

Analysis of the upstream activation sequence (UAS) of the yeast phosphoglycerate kinase gene (PGK) has demonstrated that a number of sequence elements are involved in its activity and two of these sequences are bound by the multifunctional factors Rap1p and Abftp. In this report we show by in vivo footprinting that the regulatory factor encoded by GCR1 binds to two elements in the 3′ half of the PGK UAS. These elements contain the sequence CTTCC, which was previously suggested to be important for the activity of the PGK UAS and has been shown to be able to bind Gcrlp in vitro. Furthermore, we find that Gcr1p positively influences PGK transcription, although it is not responsible for the carbon source dependent regulation of PGK mRNA synthesis. In order to mediate its transcriptional influence we find that Gcrtp requires the Rap1p binding site, in addition to its own, but not the Abf1p site. As neither a Rapip nor a Gcr1p binding site alone is able to activate transcription, we propose that Gcr1p and Rapip interact in an interdependent fashion to activate PGK transcription.

Summary This is a case report of a 67 year old man who presented with a fluctuating level of consciousness and myoclonic jerks caused in part by hypercalcaemia. The diagnosis of cerebral neoplastic angioendotheleosis was only made later on brain biopsy and is the first report of the occurrence of hypercalcaemia in neoplastic angioendotheleosis.

Regional cerebral blood flow (CBF), oxygen extraction ratio (OER), oxygen utilization (CMRO2) and blood volume (CBV) were measured in a group of 34 healthy volunteers (age range 22–82 yrs) using the 15O steady-state inhalation method and positron emission tomography. Between subjects CBF correlated positively with CMRO2, although the interindividual variability of the measured values was large. OER was not dependent on CMRO2, but highly negatively correlated with CBF. CBV correlated positively with CBF. When considering the values of all the regions of interest within a single subject, a strict coupling between CMRO2 and CBF, and between CBF and CBV was found, while OER was constant and independent of CBF and CMRO2. In ‘pure’ grey and white matter regions CMRO2, CBF and CBV decreased with age approximately 0.50% per year. In other regions the decline was less evident, most likely due to partial volume effects. OER did not change or showed a slight increase with age (maximum in the grey matter region 0.35%/yr). The results suggest diminished neuronal firing or decreased dendritic synaptic density with age.

Studies performed on 18 patients with Parkinson's disease and 6 control subjects have shown that acute administration of L-DOPA in clinically effective doses gives rise to a diffuse increase in regional cerebral blood flow without accompanying stimulation of regional oxygen utilization. The data suggest that this rise in rCBF is caused by vasodilatation due to a direct action of the drug on the cerebral blood vessels. The effect of L-DOPA on rCBF did not correlate with the degree of clinical improvement seen in each patient after treatment. The therapeutic effect of L-DOPA in the brain was not reflected in any change of regional cerebral oxygen utilization as measured by our technique. We suggest that the pharmacological actions of L-DOPA in the brain take place on at least two different levels.

Eight patients with recent cerebral hemispheric infarction were studied with positron emission tomography and the oxygen-15 steady-state inhalation and [18F]deoxyglucose techniques to obtain values of regional cerebral blood flow, oxygen consumption, and glucose metabolism. The Sokoloff equation, used to calculate glucose metabolism, was simplified to exclude the exponential terms containing the rate constants. A value of the lumped constant quoted for normal brain (0.42) was used for infarcted regions and contralateral hemisphere. Mean regional cerebral blood flow, oxygen consumption, and glucose metabolism were all significantly depressed within the infarcts compared with the mirror regions in the contralateral cerebral hemisphere. The mean fractional extraction of oxygen was low, indicating an adequate supply of oxygen for residual oxidative metabolism. Regional oxygen consumption and glucose metabolism were significantly correlated within the infarcts, but with a relationship of 2 moles of oxygen per mole of glucose--one-third that in the contralateral hemisphere and in normal brain. Although these results suggest that the metabolizing tissue of a recent cerebral infarct utilizes aerobic glycolysis, caution about the validity of this pathophysiological observation is dictated by limitations in current positron emission tomographic tracer methodology.

Computers have been used by a few anaesthetists for teaching purposes for a number of years. Well constructed programs have the capacity to realistically present material which would not be available by other teaching methods. The advent of small portable computers has made this powerful teaching aid potentially available to a much larger group. It is likely that computer aided learning has a significant future in anaesthetic training and, in particular, for continuing medical education.

Values of regional cerebral oxygen extraction ratio and oxygen utilisation obtained with the oxygen-15 steady-state inhalation technique have been found to be overestimated due to the signal from intravascular oxygen-15. A previously described method to correct for this intravascular component has been applied to a series of studies on normal subjects, and on brain tumour and stroke patients. With this correction the regional cerebral oxygen extraction ratio in normals becomes comparable to the global values previously reported with arteriovenous sampling techniques. Within the lesions of brain tumour and stroke patients, the corrections have been found to be variable and often substantial. It is concluded that failure to apply this correction may result in major errors in the values for regional oxygen extraction ratio and oxygen utilisation. This is especially true when the regional blood flow and oxygen extraction ratio of a tissue is low and regional blood volume is high.

Abnormalities in the oxidative metabolism of glucose in human cerebral gliomas have been studied in seven patients using positron emission tomography. Measurements of regional cerebral blood flow and oxygen consumption were obtained using the oxygen-15 steady-state inhalation technique. Values of regional cerebral glucose consumption were obtained using fluorine 18–labeled 2-fluoro-2-deoxy-D-glucose and a simplification of the method of Sokoloff. Functional values were obtained for regions of tumor and brain tissue in the middle cerebral artery territory of the contralateral cortex. Values of regional glucose consumption were calculated for both regions using a value of the lumped constant quoted for normal brain tissue (0.42). Tumor regional cerebral blood flow was comparable to that in the contralateral cortex, whereas regional cerebral oxygen consumption was depressed. This depression resulted in low tumor values of the fractional oxygen extraction ratio (0.21 + 0.07), indicating that oxygen supply exceeded the metabolic demand. In contrast, tumor regional cerebral glucose consumption was not depressed and regional glucose extraction ratios were similar for tumor and brain tissue. The metabolic uncoupling between regional oxygen consumption and regional glucose consumption (CMRO2/CMRGlu = 0.24 ± 0.07 ml of oxygen per milligram of glucose) is indicative of increased aerobic glycolysis.

Regional cerebral blood flow, blood volume, fractional oxygen extraction and oxygen consumption were measured by positron emission tomography in six patients with sickle cell disease to see how oxygen delivery to the brain is maintained in the presence of both anemia and a low oxygen affinity hemoglobin. Both regional cerebral blood flow and blood volume were found to be markedly increased compared to values obtained from 14 normal subjects in the same age range. The mean fractional oxygen extraction was not significantly different in the two groups. Mean oxygen consumption in the two groups was also not significantly different but low values in individual patients with sickle cell disease and the presence of atrophy on the CT-scans of three of them were suggestive of some neuronal loss in patients without any history of nervous system involvement. In view of the known high values of cerebral blood flow and metabolism in childhood, it is suggested that when compounded by anemia and abnormal red cells, a hypercirculatory state may make patients in this age-group particularly prone to ischemic infarction.

Summary A pilot evaluation of a simulation program used during a tutorial for the teaching of uptake and distribution of the inhalational anaesthetic halothane shows a highly significant improvement in the students' answers after the tutorial using a ‘before and after’ questionnaire. The students showed an understanding of the program's display and model limitations. This encourages the further use of the program.

Regional cerebral blood flow, oxygen utilisation, fractional oxygen extraction, and cerebral blood volume were measured by positron emission tomography in thirty-two patients with internal-carotid-artery occlusion. In most cases, any reduction in cerebral blood flow in the territory distal to an occluded carotid artery was matched to diminished cerebral metabolic demands. Cerebral blood flow was inappropriately low in only six patients, in whom regional oxygen utilisation was maintained by a compensatory rise in oxygen extraction ratio. The frequent finding of high cerebral blood volume distal to occluded vessels was consistent with a state of focal vasodilatation in response to diminished cerebral perfusion pressure. Analysis of the relation between cerebral blood flow, blood volume, and oxygen extraction ratio suggested that the reduction in cerebral perfusion pressure, and hence circulatory reserve, could be most reliably predicted by the ratio of cerebral blood flow to blood volume. By identifying those patients with carotid occlusion who are most compromised on haemodynamic grounds, combined measurement of cerebral blood flow and blood volume should be valuable in selection of candidates for extracranial-intracranial bypass surgery.

In order to study the relationship between regional cerebral blood flow and metabolism, it is necessary to measure these entities of tissue function independently. The use of gamma-ray-emitting radioisotopes to trace physiological/biochemical pathways, and radiation detectors placed external to the body, enables regional tissue function to be measured without disturbing the subject’s physiological state. The paper presented by Dr. Ter-Pogossian in this symposium describes how shortlived positron-emitting radioisotopes of oxygen, nitrogen, carbon, and fluorine can be used as labels for in vivo tracer studies. He also demonstrates that by positron emission tomographic (PET) scanning, the transaxial tomographic distribution of these isotopes can be recorded throughout the body. Furthermore, by applying a correction for attenuation effects, it is possible to measure absolute levels of regional tissue concentrations of tracer. This is an important aspect of PET scanning, since it enables concentrations of tracer in blood, measured from samples, to be expressed in the same units as the tracer concentration in the tissues. Thus, appropriate tracer models formulated to define the fate of the labelled molecules can be solved to derive absolute values of the physiological entity being traced.

Summary A computer aided learning program for teaching the kinetics of uptake and distribution of the inhalational anaesthetic halothane is described. The program is based on a seven-compartment model which simulates the action of halothane on ventilation and on the cardiovascular system. The program is available to the student in four forms: one with no changes in circulation or respiration, one with the cardiovascular effects of halothane included, one with respiratory effects only, and one with both of these effects combined. The student can study the importance of the influence of halothane on respiration and blood circulation by comparing results from simulations on different models. The simulation is presented as graphs which are continuously displayed on an alphanumeric visual display terminal. Interaction with the program is possible at all times to change the simulation speed, the variables being graphed, the inspired halothane fraction, and the fresh gas flow.

There is continuing controversy about the management of patients presenting with a TIA or minor stroke who are found to have occlusive disease of the carotid or vertebral arteries. Even the widespread belief in the value of carotid endarterectomy for accessible stenotic lesions has yet to be supported by a satisfactory clinical trial. There is still more uncertainty about the role of extracranial-intracranial (EC-IC) bypass surgery, although this procedure is now being widely practised in a variety of clinical circumstances. A large proportion of patients considered for EC-IC bypass have complete occlusion of an internal carotid artery (ICA), often associated with continuing symptoms referable to the ipsilateral cerebral hemisphere. These delayed ischemic episodes beyond an occluded ICA may still be explained by embolic mechanisms in many cases (Barnett 1978; Countee et al. 1980; Finklestein et al. 1980). However, in a minority of patients the clinical features are highly suggestive of a hemodynamic rather than an embolic circulatory disturbance (Shanbrom and Levy 1957; Baron et al. 1981; Stark and Wodak 1983). Ischemic events of this type, resulting from a state of critically reduced cerebral perfusion pressure (CPP), provide one of the few convincing arguments in favor of EC-IC bypass surgery. Since the majority of patients’ symptoms cannot be conveniently classified as being either embolic or hemodynamic in origin, an indirect assessment of regional CPP, and hence residual circulatory reserve, would clearly be of value.

A model is developed to interpret changes in limb volume measured during venous occlusion plethysmography. The parameters of the model are chosen to represent, as closely as possible, physiological variables related to blood flow within the limb. These parameters are shown to be related to various parameters derived by other investigators for interpreting the same measurements. An experiment is reported in which these changes in volume are inferred from measurements of the electrical resistance of limbs. It is shown that the model can accurately represent such changes in volume. A further experiment is reported which demonstrates how changes in the model parameters are related to changes in the circulatory system within a laboratory model of a limb.

Electromyographic (EMG) measurements from the forehead and rectus abdominis areas were undertaken in a group of patients presenting for elective hysterectomy. The efficacy of EMG auditory feedback as a means of inducing relaxation so as to modify the dose of postoperative analgesia was examined and compared with the dose in subjects having EMG measurements without audiofeedback. Comparison was also made with a group of subjects who did not have EMG measurements. Subjects in those groups who were given relaxation instruction received less postoperative analgesia than subjects not receiving this treatment. A reduction in EMG activity was demonstrated with auditory feedback, but this did not relate directly to reduced analgesic administration after surgery.

A review of 324 cases reported to the Anaesthetic Mortality Assessment Committee over a five year period confirms a low incidence of cases associated primarily with anaesthesia. The committee has identified potential problem areas affecting anaesthesia which require continued vigilance on the part of the anaesthetist. These include the fluid balance of patients, the potential for hypothermia, altered patterns of drug action in the elderly and critically ill and the influence of other disease processes-notably those affecting the heart. As well there are the rare problems more directly associated with anaesthesia such as hypersensitivity reactions and malignant hyperpyrexia. Technical problems during anaesthesia such as misplacement of the endotracheal tube are not commonly associated with death, but because they are preventable, are of particular importance.

Mittels Positronen-Emissions-Tomographie (PET) konnen regionale Hirndurchblutung (CBF), Sauerstoffextraktionsrate (OER), regionaler Sauerstoff verbrauch (CMR02) und regionales Blutvolumen (CBV) nicht-invasiv in absoluten Werten gemessen werden (1,3).

A survey of New Zealand public hospitals undertaken at the end of 1974 shows that the country is training half the number of anaesthetists to maintain the public hospital-based anaesthetic services. There is a need to develop and expand training programmes for anaesthetists. New graduates can be assured that there are career prospects in the specialty.

Anaphylactoid or anaphylactic reactions to drugs used during general anaesthesia are potentially life threatening. It is important that they be differentiated from other types of cardio-respiratory collapse. At present a detailed history of the time sequence of events in relation to drug administration is of a greatest importance. Retrospective skin testing may then indicate which agent was involved, although false positives and false negatives may occur. Forty-nine patients who presented with a history of collapse during anaesthesia over a five year period were skin tested. Positive results were obtained in 22, ten gave inconclusive test results but a strongly suggestive history. The remainder were considered to have other causes for their clinical presentation. The incidence of severe reactions confirmed by history and by skin testing in this community is approximately 1:4000.

Previous studies using positron emission tomography (PET) have established that the normal coupling of cerebral blood flow (CBF) and oxygen metabolism (CMRO2) breaks down in acute stroke (Ackerman et al. 1981; Baron et al. 1981; Lenzi et al. 1981). Initially, there are areas of ischaemic but still surviving brain in which CMRO2 is preserved in relation to the marked fall of blood flow; the oxygen extraction ratio (OER) is high. Prolonged severe ischaemia leads to a subsequent fall of CMRO2 (and hence also of OER) even if there is no further reduction of blood flow. This sequence of events is considered to represent the transition from potentially reversible ischaemia to established and irreversible cerebral infarction. In order to examine the relationship of regional cerebral glucose metabolism (rCMRG1u) to these pathophysiological changes, we have carried out combined, consecutive measurements of CBF, CMRO2 and CMRGIu in patients with acute stroke.

This article describes a rapid method for the regional measurement of cerebral blood flow using a single breath of C15O2 and positron emission tomography. The technique is based on the bolus distribution principle and utilises a reference table for the calculation of flow. Seven subjects were studied using both this method and the C15O2 continuous inhalation steady-state technique. The single-breath method gave flow values 20% higher than those obtained using the steady-state method. A simulation study was performed in an attempt to define the reasons for the difference between the two techniques. Estimations were made of identified sources of error in the measurement of regional cerebral blood flow using the single-breath technique and compared with results from a similar study previously described for the steady-state technique. However, further comparative studies will be necessary to satisfactorily explain the difference between both techniques.

Constant flow perfusion of the pulmonary circulation was established in isolated cat lungs. These were ventilated with 5% carbon dioxide in oxygen in order to maintain a near-normal carbon dioxide tension and acid-base status in the perfusing blood. The alteration of pulmonary vascular resistance in response to a change in inspired carbon dioxide concentration from 5% to 10% was investigated before, during and after the administration of 1% halothane (in 16 perfusions) or 5% diethyl ether (in 8 perfusions). An increase of inspired carbon dioxide concentration caused a significant increase in pulmonary vascular resistance, but the magnitude of the increase was diminished during the administration of both anaesthetic agents. The response increased again after the anaesthetics were withdrawn. The administration of halothane during ventilation with 5% carbon dioxide caused a significant reduction of pulmonary vascular resistance whilst diethyl ether resulted in a significant increase in this measurement. It is suggested that inhalation anaesthetic agents may increase ventilation/perfusion mismatching by altering the normal vasoconstrictor response to increased alveolar PCO2

In the foregoing an overview of positron emission tomography has been presented. Its theoretical, technical, and methodological implications, as well as its clinical applications have been outlined. The emphasis has been on the quantitative aspects of the method and its usefulness is investigating normal and pathological functions of brain tissue. Although the potential of this new research technique is obvious, many theoretical and practical difficulties still need to be solved. Nevertheless it provides an opportunity to bridge the gap between basic experimental research and clinical medicine.

Pulmonary dysfunction may be caused by microaggregates passing through a standard blood filter (170 mu) during transsfusion. In this study a sheep was repeatedly tranfused with a single unit (about 450 ml) of her own blood to compare the effects of 27 mu and 170 mu pore filters on lung function. Lung function was assessed by comparing cardiac output, pulmonary shunt and alveolar-arterial oxygen tension gradient before, during and after transfusion. There were no significant changes in these parameters. So far as these results can be extrapolated from sheep to man, it is considered that the more expensive 27 mu pore filter is not justified in small volume transfusions.

The development of positron emission tomography (PET) represents an important advance in the study of cerebral tissue function in man. By virtue of the characteristic double photon signal from positron emitting isotopes and tomographic reconstruction using paired coincidence detectors, precise regional measurements can be made of cerebral isotope concentration throughout a tomographic slice of brain. PET is thus a noninvasive, in vivo equivalent of the autoradiographic technique applied to experimental animals. Furthermore, the development of a variety of tracer models has led to the measurement not only of regional cerebral blood flow and blood volume, but also of local metabolic activity and its relationship to the available blood supply. Labeling of drugs and neurotransmitter precursors is further expanding the range of applications for PET in the study of both normal and abnormal cerebral physiology.

The effect of an intravenous injection of ketamine 1.1 mg/kg on the cerebrospinal fluid (c.s.f.) pressure was studied in 20 patients during nitrous oxide-oxygen and relaxant anaesthesia. In 11 patients with normal c.s.f. pathways the pressure did not alter significantly, but in 6 of 9 patients with intracranial space-occupying lesions there was a substantial rise in cs.f. pressure. These results suggest that ketamine must be used with caution in patients with intracranial space-occupying lesions.