[Guidelines for the probabilistic treatment of community-acquired pneumonia: compared experience between internal medicine and emergency departments in the University Hospital of Besançon, France]. / Application des référentiels concernant la prise en charge probabiliste des pneumopathies communautaires non sévères: expérience comparée du service de médecine interne et du service des urgences adultes du CHU de Besançon.

INTRODUCTION: The objective of this study was to assess the application of local and national recommendations in the management of community-acquired pneumonia in an internal medicine department with an antibiotic referent physician and in an emergency department. PATIENTS AND METHODS: This was a retrospective single-center study including patients admitted with community-acquired pneumonia in the internal medicine department of the University Hospital of Besançon after an initial admission in the emergency department. RESULTS: One hundred patients (58 women and 42 men) were included. The mean age was 79 ± 11 years. The prescriptions done in the emergency department were in accordance with local recommendations or Société de pathologie infectieuse de langue française (SPILF) recommendations in 62% of cases. The prescriptions followed the recommendations in 94% of cases in internal medicine department (P<0.05). The lack of initial antibiotic treatment had no influence on morbidity and mortality. CONCLUSION: The guidelines for infectious diseases treatment were significantly more often applied in a department where a referent physician was designated for this.

Spontaneous field potentials influence the activity of neocortical neurons during paroxysmal activities in vivo.

Field-potential recordings with macroelectrodes, and extra- and intracellular potentials with micropipettes were used to determine the influence of spontaneous field potentials on the activity of neocortical neurons during seizures. In vivo experiments were carried out in cats under anesthesia. Strong negative field fluctuations of up to 20 mV were associated with electroencephalogram "spikes" during spontaneously occurring paroxysmal activities. During paroxysmal events, action potentials displayed an unexpected behavior: a more hyperpolarized firing threshold and smaller amplitude than during normal activity, as determined with intracellular recordings referenced to a distant ground. Considering the transmembrane potential (the difference between extra- and intracellular potential) qualified this observation: firing threshold determined from the transmembrane potential did not decrease, and smaller action-potential amplitude was associated with depolarized firing threshold. The hyperpolarization of intracellular firing threshold was thus related to the field potentials. Similar field-potential effects on neuronal activities were observed when the paroxysmal events included very fast oscillations or ripples (80-200 Hz) that represent rapid fluctuations of field potentials (up to 5 mV in <5 ms). Neuronal firing was phase-locked to those oscillations. These results demonstrate that: (a) strong spontaneous field potentials influence neuronal behavior, and thus play an active role during paroxysmal activities; and (b) transmembrane potentials have to be used to accurately describe the behavior of neurons in conditions in which field potentials fluctuate strongly. Since neuronal activity is presumably the main generator of field potentials, and in return these potentials may increase neuronal excitability, we propose that this constitutes a positive feedback loop that is involved in the development and spread of paroxysmal activities, and that a similar feedback loop is involved in the generation of neocortical ripples. We propose a mechanism for seizure initiation involving these phenomena.

The role of chloride-dependent inhibition and the activity of fast-spiking neurons during cortical spike-wave electrographic seizures.

The conventional view is that the cortical paroxysmal depolarizing shift is a giant excitatory postsynaptic potential enhanced by various intrinsic neuronal currents. Other results point out, however, that synaptic inhibition remains functional in many forms of paroxysmal activities and that intense activation of GABAergic interneurons may accentuate the excitation of target pyramidal cells. To determine the role played by cortical inhibitory neurons in paroxysmal discharges, we used single and dual intracellular recordings from electrophysiologically identified neocortical neurons during spontaneously occurring and electrically induced spike-wave electrographic seizures in vivo. Conventional fast-spiking neurons (presumably local inhibitory interneurons) fired at a very high frequency during paroxysmal depolarizing shifts, which corresponded to the electroencephalogram 'spike' components of spike-wave complexes. The firing of fast-spiking neurons preceded the discharges of neighboring regular-spiking neurons. During electrographic seizures, the reversal potential of the GABA (type A)-mediated potentials in regular-spiking neurons was shifted to positive values by 20-30 mV. Data also show that the prolonged hyperpolarizations during the electroencephalogram 'wave' components of spike-wave electrographic seizures do not contain Cl(-)-dependent inhibitory potentials. Moreover, Cl(-)-dependent mechanisms were reduced or absent during the fast runs that are associated with spike-wave complexes in some paroxysms. We conclude that the strong activity of cortical inhibitory neurons during paroxysmal depolarizing shifts induces Cl(-)-dependent depolarizing postsynaptic potentials in target pyramidal neurons, which facilitate the development of electrographic seizures.

Focal synchronization of ripples (80-200 Hz) in neocortex and their neuronal correlates.

Field potentials from different neocortical areas and intracellular recordings from areas 5 and 7 in acutely prepared cats under ketamine-xylazine anesthesia and during natural states of vigilance in chronic experiments, revealed the presence of fast oscillations (80-200 Hz), termed ripples. During anesthesia and slow-wave sleep, these oscillations were selectively related to the depth-negative (depolarizing) component of the field slow oscillation (0.5-1 Hz) and could be synchronized over ~10 mm. The dependence of ripples on neuronal depolarization was also shown by their increased amplitude in field potentials in parallel with progressively more depolarized values of the membrane potential of neurons. The origin of ripples was intracortical as they were also detected in small isolated slabs from the suprasylvian gyrus. Of all types of electrophysiologically identified neocortical neurons, fast-rhythmic-bursting and fast-spiking cells displayed the highest firing rates during ripples. Although linked with neuronal excitation, ripples also comprised an important inhibitory component. Indeed, when regular-spiking neurons were recorded with chloride-filled pipettes, their firing rates increased and their phase relation with ripples was modified. Thus besides excitatory connections, inhibitory processes probably play a major role in the generation of ripples. During natural states of vigilance, ripples were generally more prominent during the depolarizing component of the slow oscillation in slow-wave sleep than during the states of waking and rapid-eye movement (REM) sleep. The mechanisms of generation and synchronization, and the possible functions of neocortical ripples in plasticity processes are discussed.

Natural waking and sleep states: a view from inside neocortical neurons.

In this first intracellular study of neocortical activities during waking and sleep states, we hypothesized that synaptic activities during natural states of vigilance have a decisive impact on the observed electrophysiological properties of neurons that were previously studied under anesthesia or in brain slices. We investigated the incidence of different firing patterns in neocortical neurons of awake cats, the relation between membrane potential fluctuations and firing rates, and the input resistance during all states of vigilance. In awake animals, the neurons displaying fast-spiking firing patterns were more numerous, whereas the incidence of neurons with intrinsically bursting patterns was much lower than in our previous experiments conducted on the intact-cortex or isolated cortical slabs of anesthetized cats. Although cortical neurons displayed prolonged hyperpolarizing phases during slow-wave sleep, the firing rates during the depolarizing phases of the slow sleep oscillation was as high during these epochs as during waking and rapid-eye-movement sleep. Maximum firing rates, exceeding those of regular-spiking neurons, were reached by conventional fast-spiking neurons during both waking and sleep states, and by fast-rhythmic-bursting neurons during waking. The input resistance was more stable and it increased during quiet wakefulness, compared with sleep states. As waking is associated with high synaptic activity, we explain this result by a higher release of activating neuromodulators, which produce an increase in the input resistance of cortical neurons. In view of the high firing rates in the functionally disconnected state of slow-wave sleep, we suggest that neocortical neurons are engaged in processing internally generated signals.

Disfacilitation and active inhibition in the neocortex during the natural sleep-wake cycle: an intracellular study.

Earlier extracellular recordings during natural sleep have shown that, during slow-wave sleep (SWS), neocortical neurons display long-lasting periods of silence, whereas they are tonically active and discharge at higher rates during waking and sleep with rapid eye movements (REMs). We analyzed the nature of long-lasting periods of neuronal silence in SWS and the changes in firing rates related to ocular movements during REM sleep and waking using intracellular recordings from electrophysiologically identified neocortical neurons in nonanesthetized and nonparalyzed cats. We found that the silent periods during SWS are associated with neuronal hyperpolarizations, which are due to a mixture of K(+) currents and disfacilitation processes. Conventional fast-spiking neurons (presumably local inhibitory interneurons) increased their firing rates during REMs and eye movements in waking. During REMs, the firing rates of regular-spiking neurons from associative areas decreased and intracellular traces revealed numerous, short-lasting, low-amplitude inhibitory postsynaptic potentials (IPSPs), that were reversed after intracellular chloride infusion. In awake cats, regular-spiking neurons could either increase or decrease their firing rates during eye movements. The short-lasting IPSPs associated with eye movements were still present in waking; they preceded the spikes and affected their timing. We propose that there are two different forms of firing rate control: disfacilitation induces long-lasting periods of silence that occur spontaneously during SWS, whereas active inhibition, consisting of low-amplitude, short-lasting IPSPs, is prevalent during REMs and precisely controls the timing of action potentials in waking.

Origin of slow cortical oscillations in deafferented cortical slabs.

An in vivo preparation has been developed to study the mechanisms underlying spontaneous sleep oscillations. Dual and triple simultaneous intracellular recordings were made from neurons in small isolated cortical slabs (10 mm x 6 mm) in anesthetized cats. Spontaneously occurring slow sleep oscillations, present in the adjacent intact cortex, were absent in small slabs. However, the isolated slabs displayed brief active periods separated by long periods of silence, up to 60 s in duration. During these silent periods, 60% of neurons showed non-linear amplification of low-amplitude depolarizing activity. Nearly 40% of the cells, twice as many as in intact cortex, were classified as intrinsically bursting. In cortical network models based on Hodgkin-Huxley-like neurons, the summation of simulated spontaneous miniature excitatory postsynaptic potentials was sufficient to activate a persistent sodium current, initiating action potentials in single neurons that then spread through the network. Consistent with this model, enlarging the isolated cortical territory to an isolated gyrus (30 mm x 20 mm) increased the probability of initiating large-scale activity. In these larger territories, both the frequency and regularity of the slow oscillation approached that generated in intact cortex. The frequency of active periods in an analytical model of the cortical network accurately predicted the scaling observed in simulations and from recordings in cortical slabs of increasing size.

Impact of intrinsic properties and synaptic factors on the activity of neocortical networks in vivo.

To investigate the relative impact of intrinsic and synaptic factors in the maintenance of the membrane potential of cat neocortical neurons in various states of the network, we performed intracellular recordings in vivo. Experiments were done in the intact cortex and in isolated neocortical slabs of anesthetized animals, and in naturally sleeping and awake cats. There are at least four different electrophysiological cell classes in the neocortex. The responses of different neuronal classes to direct depolarization result in significantly different responses in postsynaptic cells. The activity patterns observed in the intact cortex of anesthetized cats depended mostly on the type of anesthesia. The intracellular activity in small neocortical slabs was composed of silent periods, lasting for tens of seconds, during which only small depolarizing potentials (SDPs, presumed miniature synaptic potentials) were present, and relatively short-lasting (a few hundred milliseconds) active periods. Our data suggest that minis might be amplified by intrinsically-bursting neurons and that the persistent Na+ current brings neurons to firing threshold, thus triggering active periods. The active periods in neurons were composed of the summation of synaptic events and intrinsic depolarizing currents. In chronically-implanted cats, slow-wave sleep was characterized by active (depolarizing) and silent (hyperpolarizing) periods. The silent periods were absent in awake cats. We propose that both intrinsic and synaptic factors are responsible for the transition from silent to active states found in naturally sleeping cats and that synaptic depression might be responsible for the termination of active states during sleep. In view of the unexpected high firing rates of neocortical neurons during the depolarizing epochs in slow-wave sleep, we suggest that cortical neurons are implicated in short-term plasticity processes during this state, in which the brain is disconnected from the outside world, and that memory traces acquired during wakefulness may be consolidated during sleep.

Leading role of thalamic over cortical neurons during postinhibitory rebound excitation.

The postinhibitory rebound excitation is an intrinsic property of thalamic and cortical neurons that is implicated in a variety of normal and abnormal operations of neuronal networks, such as slow or fast brain rhythms during different states of vigilance as well as seizures. We used dual simultaneous intracellular recordings of thalamocortical neurons from the ventrolateral nucleus and neurons from the motor cortex, together with thalamic and cortical field potentials, to investigate the temporal relations between thalamic and cortical events during the rebound excitation that follows prolonged periods of stimulus-induced inhibition. Invariably, the rebound spike-bursts in thalamocortical cells occurred before the rebound depolarization in cortical neurons and preceded the peak of the depth-negative, rebound field potential in cortical areas. Also, the inhibitory-rebound sequences were more pronounced and prolonged in cortical neurons when elicited by thalamic stimuli, compared with cortical stimuli. The role of thalamocortical loops in the rebound excitation of cortical neurons was shown further by the absence of rebound activity in isolated cortical slabs. However, whereas thalamocortical neurons remained hyperpolarized after rebound excitation, because of the prolonged spike-bursts in inhibitory thalamic reticular neurons, the rebound depolarization in cortical neurons was prolonged, suggesting the role of intracortical excitatory circuits in this sustained activity. The role of intrathalamic events in triggering rebound cortical activity should be taken into consideration when analyzing information processes at the cortical level; at each step, corticothalamic volleys can set into action thalamic inhibitory neurons, leading to rebound spike-bursts that are transferred back to the cortex, thus modifying cortical activities.

Spike-wave complexes and fast components of cortically generated seizures. IV. Paroxysmal fast runs in cortical and thalamic neurons.

In the preceding papers of this series, we have analyzed the cellular patterns and synchronization of neocortical seizures occurring spontaneously or induced by electrical stimulation or cortical infusion of bicuculline under a variety of experimental conditions, including natural states of vigilance in behaving animals and acute preparations under different anesthetics. The seizures consisted of two distinct components: spike-wave (SW) or polyspike-wave (PSW) at 2-3 Hz and fast runs at 10-15 Hz. Because the thalamus is an input source and target of cortical neurons, we investigated here the seizure behavior of thalamic reticular (RE) and thalamocortical (TC) neurons, two major cellular classes that have often been implicated in the generation of paroxysmal episodes. We performed single and dual simultaneous intracellular recordings, in conjunction with multisite field potential and extracellular unit recordings, from neocortical areas and RE and/or dorsal thalamic nuclei under ketamine-xylazine and barbiturate anesthesia. Both components of seizures were analyzed, but emphasis was placed on the fast runs because of their recent investigation at the cellular level. 1) The fast runs occurred at slightly different frequencies and, therefore, were asynchronous in various cortical neuronal pools. Consequently, dorsal thalamic nuclei, although receiving convergent inputs from different neocortical areas involved in seizure, did not express strongly synchronized fast runs. 2) Both RE and TC cells were hyperpolarized during seizure episodes with SW/PSW complexes and relatively depolarized during the fast runs. As known, hyperpolarization of thalamic neurons deinactivates a low-threshold conductance that generates high-frequency spike bursts. Accordingly, RE neurons discharged prolonged high-frequency spike bursts in close time relation with the spiky component of cortical SW/PSW complexes, whereas they fired single action potentials, spike doublets, or triplets during the fast runs. In TC cells, the cortical fast runs were reflected as excitatory postsynaptic potentials appearing after short latencies that were compatible with monosynaptic activation through corticothalamic pathways. 3) The above data suggested the cortical origin of these seizures. To further test this hypothesis, we performed experiments on completely isolated cortical slabs from suprasylvian areas 5 or 7 and demonstrated that electrical stimulation within the slab induces seizures with fast runs and SW/PSW complexes, virtually identical to those elicited in intact-brain animals. The conclusion of all papers in this series is that complex seizure patterns, resembling those described at the electroencephalogram level in different forms of clinical seizures with SW/PSW complexes and, particularly, in the Lennox-Gastaut syndrome of humans, are generated in neocortex. Thalamic neurons reflect cortical events as a function of membrane potential in RE/TC cells and degree of synchronization in cortical neuronal networks.

Role of thalamic and cortical neurons in augmenting responses and self-sustained activity: dual intracellular recordings in vivo.

Progressively increasing (augmenting) responses are elicited in thalamocortical systems by repetitive stimuli at approximately 10 Hz. Repeated pulse trains at this frequency lead to a form of short-term plasticity consisting of a persistent increase in depolarizing synaptic responses as well as a prolonged decrease in inhibitory responses. In this study, we have investigated the role of thalamocortical (TC) and neocortical neurons in the initiation of thalamically and cortically evoked augmenting responses. Dual intracellular recordings in anesthetized cats show that thalamically evoked augmenting responses of neocortical neurons stem from a secondary depolarization (mean onset latency of 11 msec) that develops in association with a diminution of the early EPSP. Two nonexclusive mechanisms may underlie the increased secondary depolarization during augmentation: the rebound spike bursts initiated in simultaneously recorded TC cells, which precede by approximately 3 msec the onset of augmenting responses in cortical neurons; and low-threshold responses, uncovered by hyperpolarization in cortical neurons, which may follow EPSPs triggered by TC volleys. Thalamic stimulation proved to be more efficient than cortical stimulation at producing augmenting responses. Stronger augmenting responses in neocortical neurons were found in deeply located (<0.8 mm, layers V-VI) regular-spiking and fast rhythmic-bursting neurons than in superficial neurons. Although cortical augmenting responses are preceded by rebound spike bursts in TC cells, the duration of the self-sustained postaugmenting oscillatory activity in cortical neurons exceeds that observed in TC neurons. These results emphasize the role of interconnected TC and cortical neurons in the production of augmenting responses leading to short-term plasticity processes.

Dynamic properties of corticothalamic neurons and local cortical interneurons generating fast rhythmic (30-40 Hz) spike bursts.

Fast spontaneous oscillations (mainly 30-40 Hz) characterize cortical and thalamic neuronal networks during behavioral states of increased vigilance and depend on cell depolarization under the influence of ascending activating systems. We investigated, by means of intracellular recording and staining in vivo, the properties of fast-oscillating cortical neurons from cat's motor and association areas, some projecting to the thalamus, others with locally arborizing axons. At a given level of depolarization, 28% of our neuronal sample discharged high-frequency spike bursts (300-600 Hz) that recurred rhythmically between 20 and 50 Hz. Such fast rhythmic bursting neurons have been found in both superficial and deep cortical layers. Slight changes in membrane potential as well as synaptic activity in thalamocortical networks dramatically altered the discharge patterns, from single spikes to rhythmic spike-bursts, and eventually to fast tonic firing without frequency adaptation. Thus our data challenge the conventional idea that sharply defined, invariant features and distinct locations in certain cortical layers characterize some neocortical cell-classes. We demonstrate that the distinctions between intrinsic electrophysiological properties of neocortical neurons are much more labile than conventionally thought. The present results, which indicate that corticothalamic neurons discharge fast rhythmic spike bursts mainly at 30-40 Hz, suggest that this activity results in integrated fast oscillations within corticothalamic networks.

Retention of nursing students with English as a second language.

The purposes of this study were to: (a) determine nursing students' perceptions of the learning activities which contribute the most to their knowledge and skills; (b) determine students' perceptions of their learning difficulties; (c) compare the perceptions of English as a second language (ESL) and non-ESL students; (d) determine nursing faculty perceptions of ESL students' learning difficulties; (e) compare the perceptions of ESL students and faculty; and (f) identify needs for educational and/or supportive programmes for faculty and students. Differences in perceptions of faculty and students regarding areas of difficulty and students' needs may influence the services provided to students and therefore contribute to their lack of success and attrition. A questionnaire was given to students in the first and second years of the University of British Columbia (UBC)/Vancouver Hospital (VH) Nursing Programme to collect data regarding their high school and post-secondary education, date of arrival in Canada, first language, and their perceptions of helpfulness and difficulty of learning activities. A similar questionnaire was given to faculty members working with these students to collect data about their perceptions of areas of difficulty and activities that contribute the most to the learning of ESL students. Data analysis consisted of t-tests for statistical comparison of the responses of ESL and non-ESL students, and ESL students and faculty. The results indicated statistically significant differences between the perceptions of faculty and ESL students, particularly in the areas of difficulty. The need for educational programmes for both faculty and students was identified.

Partnership in education: working toward the baccalaureate degree as entry to nursing practice in Canada.

In the early 1980s Canadian professional nursing associations officially adopted the goal of baccalaureate entry to practice by the year 2000. In the ensuing years, nursing educators have explored a variety of means to work toward achieving this goal. This paper describes a collaborative model of baccalaureate programme delivery developed between a university school and a hospital-based diploma school in Vancouver, British Columbia. The paper documents the history of the collaboration and the organization of human and physical resources for implementation. The issues and challenges encountered in the transition, the strategies used to facilitate the process, and the benefits gained by each partner are discussed.

Protein kinase C activity and expression in normal and adenomatous human pituitaries.

Protein kinase C (PKC) activity and expression were measured in 54 adenomas (prolactin (PRL)-, growth hormone (GH)- and non-secreting), 1 of them obtained from a patient treated with the dopamine agonist bromocriptine and 2 from patients treated with the somatostatin analog octreotide. They were also measured in normal human and rat pituitaries. Total PKC activity was measured by incorporation of 32P into histones, and PKC expression by dot blot immunoquantification using purified PKC as a standard. Both enzyme activity and expression were higher in adenomatous pituitaries than in normal human or rat pituitaries. PKC expression in GH-secreting and non-secreting tumors was significantly higher than that in PRL-secreting tumors. Furthermore, it was significantly higher invasive tumors than in non-invasive tumors. In the 3 adenomas which were obtained from patients treated with bromocriptine or octreotide and which were used for PKC-activity measurement, particulate- and soluble-PKC activities were significantly lower than those measured in non-treated adenomas.

[EGF binding site number of rat anterior pituitary is increased by chronic administration with dopaminergic agonist, CV 205-502]. / Le nombre de sites EGF de l'antéhypophyse du rat est augmenté par l'administration chronique de l'agoniste dopaminergique, le CV 205-502.

In order to assess whether a chronic treatment with a dopamine agonist, CV205-502, could modulate anterior pituitary epidermal growth factor (EGF) binding sites, female Wistar rats were treated or not (controls) with CV205-502 0.25 mg/kg/day sc for 8 days. This treatment significantly reduced rats' pituitary weight and plasma prolactin levels when compared to controls (weight: 10.4 +/- 0.1 vs 11.1 +/- 0.1 mg, p less than 0.01; prolactin: 1.2 +/- 0.2 vs 4.9 +/- 0.5 ng/ml, p less than 0.01). These decreases were associated with a significant stimulation of the number of pituitary EGF binding sites Bmax: 16.7 +/- 2.3 vs 11.3 +/- 1.9 fmoles/mg proteins, p less than 0.01) with no significant effect on their affinity (Kd: 0.94 +/- 0.17 vs 0.95 +/- 0.14 nM). Therefore, the modulation of pituitary EGF binding sites might be one of the mechanisms by which the dopamine agonist, CV205-502, exerts its pharmacological effects on hormonal secretions and/or cell multiplication in the pituitary.

Effects of novel bile salts on cholesterol metabolism in rats and guinea-pigs.

Novel bile salts (quaternary ammonium conjugates) inhibited cholic acid binding and transport in everted ileal sacs in vitro. The cationic piperazine conjugate of lithocholic acid (di-iodide salt, compound 8, BRL 39924A) appeared most active, inhibiting binding by 29% and transport by 59% in guinea-pig ileum (200 microM). BRL 39924A also inhibited taurocholate uptake into guinea-pig ileal sacs and cholate uptake into rat ileal sacs and was selected for further study in vivo. In hyperlipidaemic rats, BRL 39924A significantly raised cholesterol 7 alpha-hydroxylase activity and decreased hepatic accumulation of exogenous cholic acid. HDL cholesterol concentration in the serum increased and the level of VLDL plus LDL cholesterol decreased. In hyperlipidaemic guinea-pigs. BRL 39924A lowered serum total cholesterol and triglyceride levels. Although metabolic changes were less than those achieved with the bile acid sequestrant, cholestyramine, the doses of BRL 39924A used were much lower (100-500 mg/kg body wt). Selective inhibition of receptor mediated bile acid uptake may be associated with local side-effects but these novel bile salts are useful pharmacological tools to examine the effects of receptor blockade on lipoprotein metabolism.

The effect of molecular structure in a series of merocyanines on the in vitro cytotoxicity for adenocarcinoma cells.

Preliminary results have shown that merocyanines were cytotoxic for human adenocarcinoma cells in vitro. We report the synthesis of a series of new merocyanines and the structure-effect relationship as cytotoxic agents on human adenocarcinoma cells in vitro. Some of these new derivatives were found very cytotoxic for tumor cells in vitro, whereas their systemic toxicity in vivo was very low.