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Background and purposeEpilepsy is most common in lower-income settings where access to electroencephalography (EEG) is generally poor. A low-cost tablet-based EEG device may be valuable, but the quality and reproducibility of the EEG output are not established.MethodsTablet-based EEG was deployed in a heterogeneous epilepsy cohort in the Republic of Guinea (2018-2019), consisting of a tablet wirelessly connected to a 14-electrode cap. Participants underwent EEG twice (EEG1 and EEG2), separated by a variable time interval. Recordings were scored remotely by experts in clinical neurophysiology as to data quality and clinical utility.ResultsThere were 149 participants (41% female; median age 17.9years; 66.6% ≤21years of age; mean seizures per month 5.7±SD 15.5). The mean duration of EEG1 was 53±12.3min and that of EEG2 was 29.6±12.8min. The mean quality scores of EEG1 and EEG2 were 6.4 [range, 1 (low) to 10 (high); both medians 7.0]. A total of 44 (29.5%) participants had epileptiform discharges (EDs) at EEG1 and 25 (16.8%) had EDs at EEG2. EDs were focal/multifocal (rather than generalized) in 70.1% of EEG1 and 72.5% of EEG2 interpretations. A total of 39 (26.2%) were recommended for neuroimaging after EEG1 and 22 (14.8%) after EEG2. Of participants without EDs at EEG1 (n=53, 55.8%), seven (13.2%) had EDs at EEG2. Of participants with detectable EDs on EEG1 (n=23, 24.2%), 12 (52.1%) did not have EDs at EEG2.ConclusionsTablet-based EEG had a reproducible quality level on repeat testing and was useful for the detection of EDs. The incremental yield of a second EEG in this setting was ~13%. The need for neuroimaging access was evident.

WOS: 000442229500021, PubMed ID: 30101073, Background: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. Methods: We sent a cross sectional, survey monkey (R) questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. Results: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months. 53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, >= 26 weeks in 12% and < 17 weeks in 3%. Discussion: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development., Vitaflo, We thank Vitaflo for supporting the publication cost of this paper.

Introduction Abstract presentations at scientific meetings allow rapid dissemination of novel research and enables peer review before submission for publication. The percentage of abstracts that achieve full publication, however is variable ranging between 11–78% from other medical specialty meetings. This study evaluates the conversion rate of abstracts presented at the BSG annual meeting, and comperes the outcome from this national meeting with another internationally recognised gastrointestinal meeting (UEGW). Methods All abstracts presented at the BSG between 1994 and 2008 were reviewed in Nov 2012. UEGW meeting abstracts between 2009 and 2011 were reviewed in October 2014. Review dates for both the BSG and UEGW abstracts were at least 3 years post the last meeting evaluated, which is a previously reported upper limit timescale for subsequent full publication. PUBMED and EMBASE databases were reviewed using cross-referencing of first author, senior author and at least one key word from the abstract title. Abstracts and possible full publications were then examined in tandem to ensure they represented the same study. Abstracts that were withdrawn were excluded from the study. In addition to publication rates, data was collected on lag time to publication and journal impact factors. Statistical analyses were performed using contingency tables and chi squared statistics for categorical data using SPSS version 20.0. Results Over a 15 year period (1994–2008) the conversion rate of BSG abstracts to full publication was 33.4% (2273/6798, mean impact factor of published journal = 3.8). The mean lag time until publication was 23 months, with service development abstracts having the lowest conversion rate of 6.9% (8/116). Of the 6560 abstracts presented at UEGW meetings between 2009–2011, 31.0% (2033/6560) went on to full publication in indexed journals (mean impact factor = 3.93). The mean lag time between UEG abstract presentation and full publication was 16 months. The conversion rate of BSG abstracts is broadly comparable to UEGW, however it did achieve a statistically significant difference (33.4% vs.31.0% p = 0.003). Conclusion This study demonstrates that the BSG compares favourably to another internationally recognised gastroenterology meeting with regards to the outcomes of its abstracts. Findings from this work provides reassurances to researchers that submission to the BSG annual meeting is worthwhile, and that the peer-review process provided increases the likelihood of success in achieving subsequent full publication. Disclosure of Interest None Declared

The author addresses the diagnosis of seizure disorders by discussing clinical features of the different types of seizures, including generalized tonic-clonic, absence, myoclonic, partial complex seizures, and non-epileptic or “pseudoseizures.” She also discusses the use of appropriate laboratory tests, electroencephalography, computed tomography, magnetic resonance imaging, and positron emission tomographic scanning. The rationale of and approach to treatment of these conditions with some of the common anticonvulsant drugs (phenytoin, carbamazepine, valproic acid, phenobarbital, and primidone) is provided.

The safety of biotechnological products used for medicinal products is addressed by EU council directives. The general principles and the regulatory framework for the handling of new drug applications within this areas are described both with respect to benefit/risk evaluation, quality assessment, preclinical safety and efficacy testing.

The use of automated mapping/facilities management, geographic information systems (GIS), and computer aided design-drafting (CAD) technology within the water industry was surveyed by the AWWA Computer Assisted Design Committee. Of the 270 respondents, only 20 percent indicated that they had no involvement in computerization in these areas. In addition to standard applications such as engineering drafting and facilities mapping, utilities are using raster data for document imaging and interation of raster and vectorized data and developing interfaces between GIS and other systems such as supervisory control and data acquisition, customer billing, and hydraulic models

SUMMARYMultimodality evoked potentials testing including PVEPs, SEPsand BAEPs was done in 112 patients who were known or suspected to have multiple sclerosis. The incidence of abnormal evoked potential findings in each of these systems was considered in patients in the different diagnostic categories of M.S. Results were also evaluated with respect to the presence of abnormal clinical visual, somatosensory, or brainstem signs. The PVEP was found to be the most frequently abnormal even in patients without clinical involvement in the visual system (45% of patients with definite, probable, or possible M.S.), the SEP was less frequently abnormal in the absence of clinical signs (35% in patients with M.S.), and the BA EP showed the lowest frequency of abnormalities in patients without brainstem signs (14% in patients with M.S.). Combining the three types of evoked potentials significantly increased the percentage of M. S. patients having abnormal findings, compared to any of these tests alone, with 97% of “definite” M.S. patients, 86% of “probable” M.S. patients and 63% of “possible” M. S. patients having at least one of these EP tests abnormal.

1. Parallel recordings have been made of the cervical sympathetic and carotid body chemoreceptor activity in the anaesthetized cat. 2. The sympathetic activity remains remarkably constant while the chemoreceptor activity is varied by changes in the blood gas tensions of relatively short duration. 3. Changes in intrathoracic pressure by obstruction to the airway or thoracic compression were associated with changes in the activity of both nerves. 4. It is likely that, under normal conditions, the sympathetic nervous activity provides a stable vasomotor tone within the carotid body.

1. In the sinus nerve of mature foetal sheep (120-147 days gestational age) three types of nerve activity have been demonstrated: (a) baroreceptor afferent, in which the nerve activity was synchronous with the pulse pressure wave and which followed pressure changes in the carotid sinus including those caused by compressing the umbilical cord. The discharge of nine out of twelve baroreceptor afferents increased with sympathetic stimulation, (b) a subtype of (a) in which there was irregular activity from pressure receptors which most probably represented baroreceptors discharging at or about threshold, and (c) in the older foetuses (130-147 days), there was activity which was unaffected by changes in carotid sinus pressure, Pa, O2 or NaCN but which increased in discharge rate with compression of the umbilical cord or with stimulation of the cervical sympathetic; this activity then increased with injection of NaCN and was thus identified as chemoreceptor in origin. In addition, a pathway originating in the cervical sympathetic and which passed through the superior cervical ganglion was demonstrated by evoking a compound action potential on stimulation of the preganglionic cervical sympathetic nerve. 2. Recordings from pre- or post-ganglionic cervical sympathetic nerves showed that spontaneous activity was present and increased when the umbilical cord was compressed. 3. These results suggest that the carotid body chemoreceptors in the foetus are relatively insensitive to chemical changes and that, in their activation at birth, the sympathetic could be involved. Possible neural pathways and the mechanism of activation are discussed.

1. Afferent activity was measured in the vagus nerves in sixteen foetuses within 2-3 days of natural term and in two foetuses 130 and 135 days gestational age, exteriorized by hysterotomy from seventeen ewes given either a spinal anaesthetic (ten) or pentobarbitone sodium (seven).2. Activity from aortic chemoreceptors was observed which increased in rate with foetal hypoxia, NaCN or nicotine and temporary occlusion of the umbilical cord or veins. Activity was abolished or reduced with saline equilibrated with air.3. Activity from baroreceptors was observed which was synchronous with the arterial pulse and which followed changes in arterial pressure.4. Activity designated as arising from stretch receptors in the lungs or lower airways was observed which consisted of a regular discharge at 15-45 impulses sec(-1), which varied with intra-tracheal pressure, which increased with negative intrathoracic pressure generated by spontaneous respiratory movements, which, when the umbilical cord was occluded, at first increased in rate and then fell to zero at or about the occasion of the first breath. After breathing had been established, activity assumed the rhythmical pattern and showed evidence of slow adaptation of receptors seen in the adult. This activity was frequently modulated by the heart beat and after breathing had started it was reduced when carbon dioxide was raised.5. Respiratory movements with a frequency of 10-20/min occurred spontaneously in foetuses from ewes given a spinal anaesthetic and were associated with a modulation of the stretch receptor discharge. They could be induced by withdrawing fluid from the trachea and so lowering both intra-tracheal pressure and receptor discharge and were abolished by raising intra-tracheal pressure. These changes were abolished by sectioning the vagi just caudal to the nodose ganglion.6. These results indicate that there are excitatory and inhibitory pathways in the vagus nerves which are active in the foetus and which may well be concerned with the limitation of respiratory movements of the foetus and the onset of maintained respiration at birth.

1. The respiratory response to inhaled CO(2) was measured in twenty unanaesthetized new-born lambs aged 4 hr-10 days. Measurement of resting arterial pH, P(CO2) and plasma bicarbonate showed a non-respiratory acidosis immediately after birth which was corrected in the first 24-28 hr: thereafter, the acid-base pattern was of a compensated respiratory alkalosis.2. When CO(2) was added to the inspired gases and resting arterial oxygen tension (P(a), (O2)) was controlled, the average increase in minute ventilation (V) was 0.075 l.min(-1).kg(-1).mm Hg, P(a), (CO2) (-1) and duplicate responses in the same lamb differed by 6-22.5%.3. The slope of the V/P(a), (CO2) line (S) varied inversely with P(a), (O2). In one lamb, severe hypoxia (P(a), (O2) = 21 mm Hg) caused a marked depression of the slope.4. Neither the slope S nor the horizontal intercept B of the lines was related to the age of the lamb. B was not related to pH(a) and only slightly affected by acute hypoxia. B was related to arterial [HCO(3) (-)] and values for both were reduced with the acid-base disturbances seen in the first 10 days after birth. Evidence was given which suggested that the response of the new-born lamb to inhaled CO(2) was similar to that of man acclimatized to a P(a), (O2) of 70-75 mm Hg.5. In the lightly anaesthetized lamb, bilateral section of the sinus nerves caused a small reduction in the sensitivity to inhaled 5% CO(2) in air, an increase in the respiratory lag and a reduction in the rate at which V increased.6. It was concluded that, in the new-born lamb, the carotid chemo-receptors are involved in the response to inhaled CO(2) and that hypoxia potentiates this response.

1. Carotid body blood flow (c.b.f.) and carotid arterial-carotid body venous oxygen (A-V O(2)) difference were measured and carotid body oxygen consumption calculated in twenty-six cats anaesthetized with pentobarbitone sodium, paralysed with gallamine triethiodide and ventilated mechanically.2. With the sinus nerves intact and with blood gas tensions and carotid sinus pressure within physiological limits, section of either the pre- or post-ganglionic cervical sympathetic nerve on the same side caused an average rise in c.b.f. of 9.2 mul./min, in A-V O(2) difference of 0.09 ml./100 ml. and in carotid body oxygen consumption of 0.075 mul./min.3. When the pre- or post-ganglionic cervical sympathetic nerves were stimulated, c.b.f. and A-V O(2) difference fell. The fall in c.b.f. was enhanced at high P(a, CO2); the fall in A-V O(2) difference and in calculated oxygen consumption was enhanced at low mean arterial pressure (M.A.P.) or P(a, O2).4. Following sympathectomy, a reduction of M.A.P. at constant P(a, O2) and P(a, CO2) caused a fall in c.b.f. and a commensurate rise in A-V O(2) difference so that carotid body oxygen consumption remained approximately constant.5. When P(a, O2) was altered over the range 35 to > 400 mm Hg, or P(a, CO2) over the range 27-70 mm Hg at constant M.A.P., c.b.f. changed by amounts which were similar to those observed when the sympathetic nerves were intact and A-V O(2) difference changed in the opposite direction so that carotid body oxygen consumption similarly remained constant.6. Comparison of these results with those observed when the sympathetic nerves were intact indicates that the sympathetic nerves exert a vasoconstrictor effect upon carotid body blood vessels over a wide range of blood gas tensions and arterial pressure and that they also tend to diminish the rate of carotid body oxygen consumption. The mechanisms which may be involved in this regulation are discussed.

Blood gas tensions, pH and intravascular pressures have been measured at various sites in 22 foetal sheep of gestational age 110–147 days. Umbilical venous oxygen tension did not change significantly with age. The mean pulmonary artery pressure always exceeded that in the aorta and this pressure gradient did not change with age. By contrast the umbilical arterio-venous pressure gradient increased with age. When the ewe breathed room air, the oxygen difference between uterine artery and umbilical vein was 43–62 mm. Hg. When the ewe breathed 100 per cent 02 umbilical venous P02 rose by 4–15 mm. Hg and umbilical venous pH fell by 0·04–0·07 pH units. There were no consistent changes in foetal heart rate or blood pressures. When the ewe breathed 10 per cent O2 in N2, umbilical venous P02. fell by 7–14 mm. Hg, mean pressures in pulmonary artery and aorta and the pulmonary artery/aortic pressure gradient increased as did the size of the right to left shunt across the ductus arteriosus. Heart rate invariably increased. The oxygen saturation difference between ascending and descending aorta was maintained or increased. These results suggest (1) that factors other than a diffusion barrier to oxygen are responsible for the maternal/foetal oxygen gradient and (2) that, with maternal hypoxia, there is a redistribution of blood flow in the foetus so that as high a tissue P02 as possible is maintained in coronary and cerebral circulations.

1. Twenty-seven unanaesthetized new-born lambs, 6 hr-10 days old, responded to two levels of inspired oxygen, 125 and 110 mm Hg (alveolar CO(2) being controlled) with a sustained increase in minute ventilation (V), a small increase in heart rate and a less consistent rise in systemic blood pressure.2. An increase in V was observed when arterial oxygen tension (P(a), (O2)) had fallen by 6-15 mm Hg. There appeared to be no fixed threshold of P(a), (O2) at which ventilation started to increase.3. The increase in ventilation caused by these levels of hypoxia was significantly and directly related to the age of the lamb and to its control alveolar CO(2).4. More severe hypoxia caused a progressive increase in V until P(a), (O2) was about 25 mm Hg when respiration failed. This increase at P(a), (O2)25 mm Hg was markedly potentiated when alveolar P(CO2) (P(A), (CO2)) was increased and abolished after bilateral denervation of the carotid chemoreceptors.5. Significant (10%) left-to-right shunts were found in ten out of twelve lambs lightly anaesthetized with pentobarbitone sodium, breathing air. Hypoxia diminished the left-to-right pressure gradient largely by its pressor effect on the pulmonary circulation. When inspired O(2) tension (P(I), (O2)) was 70 mm Hg, all seven lambs studied showed a reversal of the pressure gradient and evidence of right-to-left shunts (11-42%) across the ductus arteriosus.6. The implications of these findings have been discussed with reference to previous studies of the new-born response to hypoxia and it is concluded that the peripheral chemoreceptors are fully active at birth and in the new-born period.

SUMMARY:Visual evoked responses (VER) to four geometric shapes (a square, circle, el and omega) were recorded from multiple scalp locations in twelve subjects. Significant differences were found between the occipital VERs to the square and el and between the VERs to the circle and omega. Consistent differences could not be demonstrated between the responses to the square and circle or to the el and omega.The differences between the responses were quantified by three different methods, including measurement of peak latencies and amplitudes, computation of a ratio index called λ, and the performance of discriminant functions derived by Stepwise Discriminant Analysis Program (SWDA) in classifying other single trial responses. The amplitudes (but not the latencies) of a negative peak at approximately 150 msec, and a positive one at 220 msec, latency were found to be different in the pairs of shapes described. SWDA was able to separate these same pairs and classify from 63 to 68% of new trials correctly. The latency points chosen to make up the discriminant functions correlated partly with the and components that were found to be significantly different in amplitude.It is suggested that the VER differences in the earlier part of the wave-form are related to the physical properties of the stimuli, including the contrast densities in the central 1.5° of the visual field and/'or the spatial frequencies contained in the stimuli. Differences demonstrated in later parts of the VERs may reflect differences in symbolic meaning of the stimuli.

1. Respiratory responses were measured in forty-seven cats, made decerebrate or anaesthetized with pentobarbitone or chloralose-urethane, to changes in the level of CO2 infused into the inferior vena cava via an external oxygenator circuit or to changes in the volume of venous return or to the inhalation of CO2. 2. No consistent difference was found between the respiratory response to the increase in the level of CO2 infused or CO2 inhaled provided that the volume of venous return during both sets of tests was held constant at normal levels. 3. If the volume of venous return was increased and the level of CO2 infused maintained at levels such that VCO2 did not increase, ventilation increased with a fall in Pa, CO2, a response lying approximately on the isometabolic curve. 4. If the volume of venous return and the level of CO2 infusion were raised together, a spectrum of intermediate respiratory responses was obtained which reproduced all those seen in earlier papers, in muscular exercise or other hypermetabolic states. 5. None of the steady-state respiratory responses was significantly affected by bilateral vagotomy or section of the sinus nerves, though sinus nerve section slowed the responses to infused or inhaled CO2 and they were then less precisely controlled. 6. Additional experiments indicated that where CO2 was infused or inhaled, the effective stimulus to respiration was an increase in mean Pa, CO2 in proportion to the CO2 added and that the respiratory response to CO2 was enhanced by reduced blood volume. How the changes in venous return were sensed and affected respiration, remains unclear. 7. These results may explain why previous workers have obtained exaggerated respiratory responses to the infusion of CO2 and why respiration increases rapidly at the start of exercise and is then maintained at high levels without discernible change in the chemical stimulus in arterial blood.

SUMMARY:Somatosensory evoked potentials (SEPs) were recorded following trigeminal nerve stimulation in 25 normal subjects. Mucosal stimulation of the lip resulted in a reduced stimulus artefact. The three initial peaks, N13, P19, and N30, measured respectively 12.8 ± 0.9 S−3, 19.3 ± 1.4 S−3 and 28.6 ± 1.7 S−3. Blink reflex studies were also performed in most of these subjects. In 41.4% of 29 patients with established or suspected multiple sclerosis, the trigeminal SEP was abnormal. Additional use of the blink reflex raised the overall incidence of trigeminal nerve dysfunction to 51.7%. None of the patients had clinical evidence of fifth nerve involvement either historically or on examination. Four of seven patients with progressive spinal MS and two patients whose only deficit was that of optic neuritis, had abnormal trigeminal SEPs. It is concluded that occult involvement of the pontine fifth nerve structures occurs frequently in MS despite the rarity of corresponding clinical findings. The trigeminal SEP is a useful additional neurophysiological method.

A structure has been found consistently in the wall of the internal carotid artery of the rat as it passes through the carotid canal. It consists of modified smooth muscle cells arranged longitudinally which exhibit abundant pinocytosis and are located close to endothelial cells, with which they make contact. These cells do not appear to be innervated. The closeness of this structure to the arterial lumen, into which it may actually protrude, suggests that it may be sensitive to vaso-active substances in arterial blood. If so, it is well place to affect cerebral blood flow.

1. A rapidly responding CO2 sensor and cuvette were placed in the carotid artery of anaesthetized cats and changes of PCO2 in post-pulmonary capillary blood were recorded when flow through the cuvette was suddenly stopped. 2. Under control conditions when the cats breathed spontaneously or were ventilated artificially, stop-flow caused Pa, CO2 to decay by 2--5 mmHg reaching a new equilibrium in 10--15 sec. The amount by which CO2 decayed was reduced by the inhalation of high O2. The decay was enhanced by hypoxia, the inhalation or infusion of CO2. It was reversed by the administration of acetazolamide: now with stop-flow, Pa, CO2 rose by 8--15 mmHg. 3. the mechanism of this decay is uncertain. We propose that it is due to the transfer of CO2 from plasma to red cells in post-capillary blood in response to the reduction of [H+]i as H+ binds to Hb following the oxylabile release of CO2 from Hb.

1. The blood supply to the medulla was determined by the injection of indian ink via the vertebral arteries. Virtually the whole medulla was supplied by penetrating vessels from the ventral surface. The highest density of small arterioles and venules was found close to the roots of XII and on the ventrolateral surface. 2. The pH of extracellular fluid (pHe.c.f.) was measured with pH microelectrodes of tip size 1-3 μm in cortex and medulla in seventeen cats, anaesthetized with pentobarbitone or a chloralose—urethane mixture. Parallel measurements were made of the pH of c.s.f. and plasma, the DC potential between plasma and brain and ventilation or phrenic nerve discharge. 3. In the majority of tests under steady conditions, the pH of e.c.f. was found to be lower than that of c.s.f. by between 0·03 and 0·08 units. No systematic pH gradients could be found to a depth of 5 mm beneath the surface of either medulla or cortex. 4. When plasma PCO2 was altered, pHe.c.f. changed with a latent period and speed of response related to the density of blood vessels. In vascular areas of the medulla and in the cortex, the latent period of 4 sec and the change of pHe.c.f. coincided with changes in ventilation. Changes in pHc.s.f. over the same areas were invariably slower. 5. CO2 buffering capacities were in the order plasma > e.c.f. > c.s.f. Typical values were respectively, -2·2, -2·1 and -1·6. 6. The pH of e.c.f. was unaffected by the intravenous injection of H+ and only slowly by the injection of HCO3-. Only up to a depth of 1 mm beneath the surface was pHe.c.f. affected by superfusion of mock c.s.f. in the range 6·8-8·0 units. This response had a latent period of 2-3 min and was complete in 15 min. 7. The pH of e.c.f. fell with hypoxia after a latent period of > 1 min and if all vasosensory nerves had been cut, pHe.c.f. was markedly affected by changes of blood pressure. 8. These results indicate that even under steady conditions, the pH of e.c.f. and c.s.f. is not identical, that pHe.c.f. is more obviously affected by changes in Pa, CO2 than pHc.s.f. and that putative H+ sensors which drive respiratory neurones are likely to be similarly affected.

Cerebral blood flow was measured using 133 xenon in forty-five baboons lightly anesthetized with pentobarbital. Blood flow varied between 62 and 82 ml/100g/min in gray matter and between 15 and 21 ml/100g/min in white matter. Hypercapnia and hypoxia caused a rise in blood flow and a fall in vascular resistance. Blood flow was independent of mean arterial blood pressure over the range 60 to 130 mm Hg. Section of the cervical sympathetic nerve enhanced the vascular response to CO 2 . Stimulation of the sympathetic nerve caused a reduction in blood flow in proportion to the initial blood flow. Similarly, after sympathectomy, blood flow was uniformly higher than control over the range of Pa o 2 tested (35 to 450 mm Hg). After sympathectomy, blood flow was little different from control at low blood pressure but was higher within the physiological range and blood flow then fell steadily as pressure was reduced. When the carotid, vagus, and aortic nerves were cut in the neck, the blood flow response to hypoxia and hypercapnia was reduced, and when the aortic or vagus nerves were stimulated centrally, blood flow increased independently of Pa CO 2 . Section of the seventh cranial nerve caused small and variable changes in blood flow, but if the vagus nerves had previously been sectioned, stimulation of the seventh cranial nerve caused an increase in blood flow in some of the tests. These results indicate that cerebral blood vessels are under reflex control. Possible receptors and pathways involved are discussed.

1. Carotid body blood flow (c.b.f.), the arterio-venous oxygen (A-V O(2)) difference and oxygen consumption were measured in forty-seven cats, anaesthetized with pentobarbitone, paralysed with gallamine and ventilated artificially. Carotid sinus and cervical sympathetic nerves were intact throughout.2. A system for perfusing the carotid body artificially with blood is described and evidence is given which shows that similar results were obtained whether the carotid body was naturally or artificially perfused.3. With arterial pressure, blood gas tensions and pH within physiological limits, c.b.f. varied between 33 and 68 mul./min, average 41.5; A-V O(2) difference between 0.21 and 0.46 ml./100 ml., average 0.34, and calculated oxygen consumption between 0.115 and 0.195 mul. O(2)/min, average 0.147.4. With constant mean arterial pressure, hypoxia (30-40 mm Hg P(a, O2)) or hypercapnia (> 50 mm Hg P(a, CO2)) resulted in a small increase of c.b.f., up to 14 mul./min above control; an average fall of A-V O(2) difference by 49% of control and an average fall of oxygen consumption by 36% of control.5. Carotid body blood flow fell linearly with mean arterial pressure over the range 100-170 mm Hg, the slope of the curve varying between 0.78 and 1.22 mul. min(-1). mm Hg(-1). M.A.P. A-V O(2) difference was unaffected so that oxygen consumption fell in proportion to c.b.f.6. It is concluded that the unique response of the carotid body to these stimuli is a fall in oxygen consumption and that this bears a closer relation to the known pattern of chemoreceptor discharge than do changes in total blood flow.

1. Respiratory responses to altered P(a, O2) at constant P(a, CO2) and altered P(a, CO2) at constant P(a, O2) were measured in fourteen unanaesthetized ducks 5-9 weeks old.2. All the ducks responded to the inhalation of a few breaths of 100% O(2) with a fall in V(E) of between 11 and 17% of control, and to the reduction in P(a, O2) from control levels (93-101 mm Hg) to 38-47 mm Hg with an average increase in V(E) of 190% of control which was potentiated by raising the level of CO(2).3. Ventilation approximately doubled when P(a, CO2) was raised to 55 mm Hg, the greatest sensitivity to changes in P(a, CO2) being over the range 40-45 mm Hg.4. Carotid body denervation was carried out in nine ducks and the respiratory responses were modified. The fall in V(E) with inhalation of 100% O(2) was abolished in all ducks and the rise in V(E) with hypoxia was abolished in six. The increase in V(E) as P(a, CO2) was altered in steps was unaffected but the rate at which V(E) increased in response to 4% CO(2) was markedly reduced.5. It is concluded that the chemoreceptor regulation of respiration in ducks is similar to that observed in non-diving animals.

1. The activity in carotid body chemoreceptor afferent fibres in the cat has been recorded and found to have a rhythm with the same period as respiration. 2. This rhythm is not an artifact; it is not due to arterial pressure changes with respiration nor to cyclical changes in pulmonary venous admixture. It is caused by changes in blood gas tensions during each respiratory cycle. 3. The amplitude of the rhythm is modified by transient and long-term changes in inspired oxygen or CO2 so that a rise or fall in O2 or CO2 tensions of arterial blood (Pa,O2, Pa,CO2) from the physiological range reduces it. The ratio of the rhythm amplitude to the mean rate of chemoreceptor discharge increases with Pa,O2 over the range 40-240 mm Hg. 4. The rhythm is modified by changes in respiratory frequency and volume. 5. The fluctuations of arterial oxygen tension which have the same period as respiration are shown to be conducted up the vertebral artery at least as far as the vertebro-occipital anastomosis. 6. It is proposed that the chemoreceptor rhythm reflects the moment to moment changes in blood gas tensions.

1. Methods are described for measuring tidal volume and frequency, end-tidal CO(2), blood pressure and heart rate, and arterial gas tensions in the unanaesthetized new-born lamb.2. The resting values of minute ventilation (V)/kg body wt. and arterial oxygen and carbon dioxide tension, (P(a, o2)) and (P(a, CO2)) were similar to those which have been reported in the new-born baby. There was a direct and significant relation between P(a, o2) and P(a, CO2) and the age of the lamb.3. Thirty-five unanaesthetized lambs aged 40 min to 10 days breathed 100% oxygen; minute ventilation fell by an average of 19% of control, end-tidal CO(2) increased and the ratio of change in tidal volume (DeltaV(T)) to change in pressure (DeltaP) (DeltaV(T)/DeltaP) remained constant. In a proportion of lambs, a small decrease in blood pressure and heart rate was observed. The effect of breathing 100% O(2) on lung compliance was variable.4. These changes in ventilation were virtually abolished after both sinus nerves had been cut.5. The results therefore suggest that a significant hypoxic drive to ventilation exists in the new-born lamb and that this drive is mediated by functioning and mature peripheral chemoreceptors.6. Preliminary evidence suggested that, on 100% O(2), the sensitivity of new-born lambs to inhaled CO(2) was reduced.

1. Tidal volume, carotid artery oxygen tension (Pa,O2) and blood pressure and chemoreceptor activity in the sinus nerve have been continuously measured and recorded in nine lambs anaesthetized with pentobarbitone sodium, and varying in age from some minutes after birth to 5 days after birth. 2. Inhalation of 100% oxygen caused, after a delay of 3-4 sec, a rise in Pa,O2, a fall in minute ventilation (V) and chemoreceptor activity. The respiratory response was abolished after section of both sinus nerves. 3. Inhalation of 10% oxygen in nitrogen caused a fall in carotid Pa,O2, a rise in respiration and in chemoreceptor activity. The respiratory response was abolished after both sinus nerves had been cut. 4. Minute ventilation, carotid Pa,O2 and chemoreceptor activity increased on breathing 5% CO2 in air. Section of both sinus nerves did not affect the maximum increase in ventilation but the lag of the respiratory response approximately doubled while respiration increased more slowly. 5. From these results, it was calculated that the chemoreceptors had a latency of 0·25-0·5 sec and the time constant of the rate of change of chemoreceptor activity was 10-15 sec. 6. The chemoreceptors responded to changes in Pa,O2 of ±5-10 mm Hg. 7. Comparison of these results with those reported in adult animals suggest that the peripheral chemoreceptors are fully mature at birth, that their response does not differ with the age of the lamb and that the carotid body chemoreceptors are concerned both in the mediation of the hypoxic drive to ventilation and in the respiratory response to inhaled CO2.

Cerebral blood flow was measured with xenon 133 in 21 fetal sheep and 14 newborn lambs under 48 hours old. When the ewe breathed air, the average gray matter blood flow in the fetuses was 70.6 ml/100 g/min, the average white matter blood flow 15.4 ml/100 g/min and average gray matter oxygen consumption 2.06 ml/100 g/min. The corresponding values in the newborn lambs were 87.2, 17.8, and 2.98 ml/100 g/min. A reduction of fetal Pao 2 by 7 to 11 mm Hg at a constant Paco 2 or an increase of Paco 2 at constant Pao 2 caused a rise in blood flow and arterial pressure and a fall in vascular resistance. Intravenous catecholamines caused variable changes in blood flow but no significant change in gray matter oxygen consumption. Occlusion of the umbilical cord caused an average increase in gray matter blood flow of 50% of control, in white matter blood flow of 30%, and in gray matter oxygen consumption of 90%. By the end of the first hour, these values had fallen and were then similar to those seen in the newborn lamb. These changes were not seen in fetuses in which both vagi had been cut nor in two fetuses with a failing circulation.

1. The anatomy of the carotid body and its afferent nerve supply was studied in the duck and a method of denervating the carotid body which ensures a satisfactory post-operative course is described. 2. The effect of denervating the carotid body upon the cardiac response to immersion of the head in water was studied in ten ducks which at the time of the test were unanaesthetized. 3. When the nerves were intact, immersion of the head caused a fall in heart rate after a latent period of between 1 and 9 sec to an average of 24% of the resting rate after 30 sec. Simultaneous measurement of arterial oxygen tension (Pa, O2) in the brachiocephalic artery showed a rapid initial fall during the initial 10 sec from control levels, 93-103 mm Hg, to between 42 and 47 mm Hg, followed by a gradual fall of 3-5 mm Hg for each subsequent 30 sec period of submergence. 4. Following carotid body denervation, the latent period before heart rate started to fall was no different from control but the average fall in heart rate was now to 90% of the resting rate and brachiocephalic Pa. O2 continued to fall steadily during submergence reaching levels of between 10 and 21 mm Hg by the end of the second minute. 5. Stimulation of the central end of branches of the IXth (glossopharyngeal) nerve supplying the glottis caused apnoea and bradycardia. 6. It is concluded that apnoea and bradycardia during submergence in the duck is initiated reflexly from receptors in the nares, pharynx and glottis but that the profound degree of bradycardia and mechanisms which maintain a relatively high Pa, O2 are regulated by peripheral chemoreceptor activity.

1. The responses of single afferent fibres of carotid body chemoreceptors to independent changes in arterial O2 and CO2 tensions and pH were studied in the cat in vivo. 2. The response curve obtained relating chemoreceptor activity to changes in arterial PO2 was similar to an hyperbola; the frequency of nerve impulses at first decreased rapidly as the Pa,O2 was raised and then more slowly. The arterial PO2 at which the slow decrease was reached varied among the different fibres; the mean level was 190 mm Hg ( S.D. ± 40 mm Hg). 3. Single chemoreceptor afferent fibres continued to discharge even when the arterial PO2 was more than 600 mm Hg. 4. The discharges of single chemoreceptor afferent fibres increased both with increasing Pa,CO2 at constant pH and Pa,O2, and with increasing arterial H+ at constant Pa,CO2 and Pa,O2. 5. It is concluded that single carotid body chemoreceptor afferent fibres of the cat can be activated in vivo by an increase in either arterial H+ or arterial PCO2 as well as by a decrease in arterial PO2.

1. Recordings have been made of the activity in carotid body chemoreceptor afferent fibres and in the cervical sympathetic of the cat during passive movement of the hind limbs. 2. The chemoreceptor activity increases immediately the limbs are moved and is maintained at a raised level with preservation of the chemoreceptor rhythm fluctuations throughout. In some cases, the increase persists for a time after the movements are stopped. 3. This early change does not occur if the cervical sympathetic on the same side as the carotid body from which recordings are made is cut, nor does it occur if the femoral and sciatic nerves are cut. 4. The carotid artery oxygen tension (Pa, O2) increases early; in the majority of experiments, there was no significant change in end-tidal PCO2 although the minute volume of ventilation (V) increased by about 20% of control with passive movement of the hind limbs. 5. Passive movement of the hind limbs also causes an immediate rise in cervical sympathetic activity which is sustained, and which is abolished if the femoral and sciatic nerves are cut. 6. Electrical stimulation of the cervical sympathetic causes an increase in chemoreceptor afferent discharge. 7. Bilateral cervical sympathectomy causes the respiratory lag to increase from approximately 1 sec to some 20 sec and, when passive movements cease, the fall in V is more sluggish than control. 8. These results are discussed in the light of the controversy regarding humoral and neurogenic causes for the increase in respiration in exercise.