Consciousness and disturbances of consciousness

Summary The problem of consciousness is discussed briefly, including the contrary views of consciousness as a transcendental phenomenon and as an animistic fiction. Measurement of consciousness is possible only indirectly by means of quantitative assessment of accompanying behavioral deficits.Knowledge of the structural basis of consciousness is incomplete. The ascending reticular activating system (ARAS) is necessary for the maintenance of the state of consciousness. The monoamine and a great number of descending projections modulate the ARAS. The contents of consciousness depend also on telencephalic structures, primarily on the telencephalic cortex. Certain localized telencephalic lesions bring about disturbances of consciousness. The role of the corpus callosum in the problem of consciousness is discussed (one brain—two minds hypothesis).Then a classification of the various disturbances of consciousness is proposed. The term disturbances of vigilance is used for all disturbances of consciousness which are caused by a lesion in or a functional disorder of the ARAS or any of its modulating subsystems. The term disturbances of the contents of consciousness refers to disturbances of consciousness due to global or localized lesions or functional disorders of telencephalic structures. A list of characteristic features is given for each class of disturbance of consciousness.

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Zusammenfassung Das Problem Bewußtsein wird kurz skizziert. Dabei werden die gegensätzlichen Auffassungen über Bewußtsein als transzendentales Phänomen bzw. als animistische Fiktion erörtert. Die Messung von Bewußtsein ist indirekt nur über die Bestimmung des begleitenden Verhaltensdefizits möglich. Die Kenntnis über die strukturellen Grundlagen des Bewußtseins ist lückenhaft. Für die Aufrechterhaltung des Bewußtseinsgrades kommt dem aufsteigenden retikulären aktivierenden System (ARAS) eine notwendige — wenngleich nicht hinreichende — Bedeutung zu. Das ARAS wird durch monoaminerge und eine große Zahl vom Großhirn absteigender Projektionssysteme moduliert.Telenzephale Strukturen und vor allem der telenzephale Kortex scheinen für die Entfaltung von Bewußtseinsinhalten unentbehrlich. Auch umschriebene telenzephale Läsionen können partielle Störungen der Bewußtseinsinhalte verursachen. Die Bedeutung des Balkens für das Bewußtsein wird diskutiert (one brain—two minds-Hypothese).Im letzten Abschnitt wird eine Taxonomie der verschiedenartigen Bewußtseinsstörungen versucht. Unter dem Begriff Vigilanzstörungen werden alle Bewußtseinsstörungen zusammengefaßt, die durch Läsion oder Funktionsstörungen des aufsteigenden retikulären aktivierenden Systems (ARAS) — einschließlich seiner modulierenden Subsysteme — bedingt sind. Unter Störung der Bewußtseinsinhalte werden Bewußtseinsstörungen verstanden, die durch globale oder lokale Läsion bzw. Funktionsstörung telenzephaler Strukturen verursacht werden. Für beide Klassen von Bewußtseinsstörungen wird ein Merkmalskatalog beschrieben.

     

Laminar organization of the extraocular muscles of the rabbit.

Studies of bilateral hemispheric somatosensory evoked potentials (SEP) were carried out on 17 comatose patients following closed-head injury. Control evoked potentials were obtained from 74 normal volunteers. A prognosis of potential recovery or nonrecovery from coma was made in all 17 patients based on the SEP analyses. All subjects underwent bilateral median and peroneal nerve stimulation and responses were averaged from scalp electrodes placed over the somatotopic sensory cortex for the wrist and leg. The prognostic outcome of all 17 patients was accurately predicted following SEP analysis. Results show that 4 of 17 patients with prognoses of “positive recovery” had eight defined SEP peaks present within a time base analysis of 300 ms. Twelve patients with prognoses of “negative recovery” had five or less SEP peaks present within a time base of 500 ms. The majority of the “negative recovery” patients showed only SEP primary waveform components consisting of two peaks. The data suggest a potentially useful method using SEP analysis to prognosticate the possible recovery from clinical coma.     

How do normal subjects learn a simple adaptative task: How and why do paranoid schizophrenic patients fail?

Summary The authors studied the behavior of normal subjects and paranoid schizophrenic patients in a simple problem-solving situation. The schizophrenics were divided into two sample groups, one of individuals under treatment and the other of individuals not under treatment.The learning process involved in this problem-solving situation is very similar to an instrumental conditioning, and can be understood by means of the following assumptions: (1) the subjects use decision functions in reacting to the stimuli, although they may be not fully aware of this; (2) learning is the result of successive transformations of these decisions in the course of time; (3) the changes have specific probabilities and are related to (a) those responses which are made to the latest stimuli, and (b) a differential probability for decision functions which were effective, or only interrupted painful reinforcement, or were completely ineffective.In schizophrenics further factors of importance were (1) an inertia factor and (2) the rigidly continued use of unsuccessful or only partially successful decision criteria.The authors used a systems theory based on Galois field theory and a calculus of operators specifying three groups of subjects. A computer program based on these hypotheses was tested in a simulation experiment.The statistical evaluation of the results showed a congruence between the theoretical approach and the experimental data.This work was carried out with financial support from the Institute de Alta Cultura, Lisbon, between 1970 and 1974     

Denervation supersensitivity of the urethra to α-adrenergics in the chronic neurogenic bladder

Summary The response of the urethral pressure profile to the administration of various autonomic drugs was compared between a group of eight patients with chronic neurogenic bladder as evidenced by denervation supersensitivity to besacholine^R and a group of 10 control subjects. A supersensitive response to the administration of an -stimulant with a rise of maximum urethral pressure of 10 mmHg or more above the control urethral pressure was uniformly observed in the urethra of patients with chronically denervated bladders. Mechanisms of supersensitivity are postulated and the significance of -adrenergic innervation of the urethra are stressed. These results appear to add pharmacological evidence of -adrenergic predominance in the urethra which is now believed to be dually innervated.     

Hemispherectomy — 25 years later — findings and concepts

Summary In the first part the case of a then 27 year old female patient with right-sided infantile spastic hemiplegia after left-sided porencephaly is described, in whom hemispherectomy was performed 25 years ago. The postoperative state and the development are described as well as the social outcome and the present neurological status. A computer-tomogram shows the actual state of the brain.The second part is devoted to a scientific discussion of the supplementary motility after pyramidal lesions which is defined as the action of descending subcortico-spinal pathways starting probably in the mesencephalon, whereas an ipsilateral pathway is unlikely. Comparative neurological experiments serve to support such a concept as well as similar observations in traumatic cerebral lesions in man. In the light of the far more skilled motility in cerebral lesions of the young as well as the possibility of a shift of neuropsychological functions of the dominant to the contralateral hemisphere in children up to the age of 8–10 the possibility is discussed that plasticity — the concept of Albert Bethe — could form the mechanism of auxiliary function.Furthermore the surprising sensory performances in some of the patients with hemispherectomy are emphasized and the possibilities of anipsilateral substratum are discussed; however, this contrasts with the concepts formulated for the auxiliary motility after pyramidal lesions. Clarification of these problems will probably follow only after further experimental work.

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Zusammenfassung Im ersten Teil der Arbeit wird der Fall einer damals 27-jährigen Patientin beschrieben, die eine rechtsseitige infantile spastische Hemiplegie nach linksseitiger Porencephalie hatte. Bei ihr war 25 Jahre zuvor eine Hemisphärektomie durchgeführt worden. Der postoperative klinische Status und die Entwicklung der Syndrome wird beschrieben und über die soziale Situation berichtet. Schließlich wird der derzeitige neurologische Status genau wiedergegeben. Erstmalig zeigt ein Computer-Tomogramm den Zustand des Hirns nach diesem Zeitraum.Im zweiten Teil der Arbeit wird die Entstehung der Ersatz-Motilität diskutiert, die als eine Aktion deszendierender subkortiko-spinaler Bahnen definiert wird, die wahrscheinlich vom Mittelhirn ihren Ausgang nehmen, während die Tätigkeit ipsilateraler Systeme für unwahrscheinlich gehalten wird. Vergleichende Tierexperimente am Hirn unterstützen eine solche Auffassung, ebenso wie auch die Beobachtung bei umschriebenen Hirnverletzungen des Menschen.Dann wird die Möglichkeit von Ersatzfunktionen durch Plastizität diskutiert — ein Begriff von Albert Bethe. Dies erscheint im Lichte vieler Beobachtungen wichtig, da die Ersatz-Motilität bei Hirnläsionen junger Menschen sehr viel höhere Geschicklichkeit ermöglicht als bei Läsionen von Älteren; weiter ist zu beachten, daß neuropsychologische Funktionen bei einer Hirnläsion vor dem 8. bis 10. Lebensjahr von einer dominanten Hemisphäre noch auf die andere Seite verlegt und dort lokalisiert werden können. Schließlich wird bei diesen Patienten auf die erstaunlichen Fähigkeiten der sensiblen Systeme nach Hemisphärektomie hingewiesen und hier die Möglichkeit eines ipsilateralen anatomischen Apparates diskutiert. Jedoch können bei der Sensibilität so genaue funktionell-morphologische Vorstellungen noch nicht formuliert werden, wie sie sich z. Zt. schon für die Ersatz-Motilität nach Pyramidenbahnläsion ergeben. Erst genauere Experimente im Tierversuch können weitere Aufklärung bringen.

     

Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations

According to linear pharmacokinetics, the time course of plasma concentration of a drug, C_p,is expressed by a sum of exponential functions, C_p= _i=1 ⁿ a_i .This article describes a statistical technique to estimate the number of exponential terms, n,for the time course of drug by the application of Akaike's information criterion (AIC). Plasma concentrations of ethoxybenzamide, sulfisoxazole, bishydroxycoumarin, and diazepam measured following bolus intravenous injection were used as clinical examples for this method. Selection of models is compared between the AIC method and an Ftest method at significance levels of 5% and 1%.     

Heterotopic brain tissue in the submandibular region and lung

Summary Two cases of extracranial heterotopia of the brain are reported. Case 1, in an otherwise normal female baby, had a brain heterotopia in the submandibular region. Case 2, in a still-born female baby with anencephaly, had the heterotopia in the lung. The lesion in case 1 is believed to be an encephalocele that has been pinched off through a cleft in the bone or through a foramen of the skull; the pathogenesis is similar to that of the so-called nasal glioma. Concerning the pathogenesis of case 2, contrary to the generally supported embolism theory, observation of serial sections of the tumor in the lung favors the aspiration theory according to which amniotic brain tissue fragments, which are dislocated into the amnion because of nonclosure of the ventricle or following destruction of the fetal brain, are aspirated by fetal respiratory movements in the 4th to 6th month of intrauterine life.     

Noradrenaline transport by rat heart sympathetic nerves: A re-examination of the role of sodium ions

Summary The effect of sodium ion on ³H-(–)-noradrenaline (0.0875 to 0.5 M) transport by rat heart atrial hemi-appendages incubated in vitro has been studied, and the following observations made: a) When sodium was omitted (choline and lithium substitution) there was no evidence for active noradrenaline transport, and only a component that did not show saturation kinetics up to 1 M noradrenaline, remained. b) Omission of sodium or addition of 4×10^–5 M desipramine inhibited noradrenaline transport to exactly the same extent, and their effects were not additive. Alprenolol did not reduce this sodium-independent transport, but tropolone lowered it somewhat. c) No evidence for corticosterone-sensitive noradrenaline transport (uptake-2) was found in this preparation at the low amine concentrations used. d) In control medium, the kinetic parameters of transport were: K _m: 0.59 ± 0.063 M and V _max: 2.44 ± 0.43 (pmoles/mg protein/min). With 26 mM sodium and the rest substituted by choline, K _m:2.26 ± 0.70 M (P0.001) and V _max: 2.74 ± 0.43 (pmoles/mg protein/min) (not significant). Also with 26 mM sodium, but with sucrose substitution, K _m: 0.76 ± 0.13 M (N.S.) and V _max: 1.06 ± 0.13 (pmol/mg/min) (P<0.05). Such results indicate that sodium only modifies the affinity of the transport system for noradrenaline, without changing V _max, and that changes in the latter are only a consequence of a reduction of the ionic strength. e) When noradrenaline transport was studied at different concentrations of external sodium, at constant ionic strength and with precautions to minimize the noradrenaline-releasing effect of low sodium, it was found that the data could be best represented by two hyperbolas placed in series. This suggests that the noradrenaline carrier has two sites for sodium, that do not interact with each other. When the same experiments were repeated in the absence of chloride, it was found that the noradrenaline transport system had lost virtually all its affinity for sodium. f) The effect of prolonged tissue incubation in the absence of sodium was found to produce a relatively small inactivation of noradrenaline transport. Such phenomenon was enhanced by raising the calcium concentration to 2 mM.     

Further studies on the extraneuronal uptake and metabolism of isoprenaline in the perfused rat heart

Summary To simultaneously determine the kinetics of removal, O-methylation and accumulation of ³H-isoprenaline, isolated rat hearts were perfused for 4 min with various concentrations of ³H-isoprenaline. The apparent K _m for the O-methylation of ³H-isoprenaline (3.3±0.5 M) was more than one order of magnitude lower than the corresponding value for the accumulation of unchanged amine (71.3±7.1 M). The apparent K _m for removal was very similar to that for accumulation (63.2±5.9 M). At perfusion concentrations higher than 25 M, i.e. when O-methylation was saturated, removal virtually equalled accumulation. However, at low substrate concentrations removal of ³H-isoprenaline was overwhelmingly followed by O-methylation; this led to a marked difference between rates of removal and those of accumulation.When initial rates of uptake of ³H-isoprenaline were determined after 1.5 min of perfusion of the hearts by the method of Graefe et al. (1978), the uptake of ³H-isoprenaline consisted of two components: a nonsaturable and a saturable (after subtraction of the nonsaturable component from the total uptake).The kinetic constants of the saturable component of uptake were higher than those obtained after 4 min perfusion (see above) (K _m : 110±19 M; V _max: 80±4 nmoles·g^–1·min^–1).Corticosterone competitively inhibited the saturable component of uptake of ³H-isoprenaline (K _m : 1.2 M).During wash out of accumulated ³H-isoprenaline, O-methylation took place predominantly in one of the two extraneuronal compartments. The efflux of 3-O-methyl-³H-isoprenaline (³H-OMI), the O-methylated metabolite of ³H-isoprenaline, was characterized by a half time of about 1.2 min. O-methylation accelerated the loss of radioactivity from the tissue during wash out.The extraneuronal uptake of ³H-isoprenaline was characterized as a pump and leak system by means of steady-state kinetics of accumulation of ³H-isoprenaline. Half saturation of the steady-state accumulation was observed at a concentration of 104.5 ±18.5 M ³H-isoprenaline; the leak component was characterized by a rate constant of 0.0359 min^–1.This study was supported by the Deutsche Forschungsge-meinschaftA preliminary account was presented at the 6th International Congress of Pharmacology (Graefe et al., 1975)     

Study of a new oral beta-adrenergic drug,clenbuterol, in patients with chronic bronchitis

Summary In a double-blind, placebo-controlled, incomplete cross-over study the bronchodilator, cardiovascular, respiratory and metabolic effects of 3 different oral doses of clenbuterol were studied in 12 patients suffering from partly reversible airways obstruction due to chronic bronchitis. The ventilatory response to oral clenbuterol or placebo was assessed by measurement of specific airway resistance (sRaw) to detect changes in central airways, and of flow at 85% of vital capacity ( _{85% VC}) to detect change in peripheral airways. Clenbuterol 20, 30 and 40 µg produced a significant decrease in sRaw between 15 and 480 min after administration. Its effect on the large airways was not related to the dose. Clenbuterol 30 and 40 µg caused a significant increase in _{85% VC} between 60 and 480 min after administration. After 20 µg a significant improvement in _{85% VC} was found between 120 and 240 min. The over-all effect of 30 µg on the small airways was significantly more pronounced than that of 20 µg and was more sustained than that of 40 µg 120 min after administration. No significant changes in heart rate, ECG or blood pressure were noted. Decreases in PaO₂ and O₂-saturation after clenbuterol were not related to dose. Slight falls in PaO₂ and O₂-saturation were also observed after placebo. These observations are briefly discussed. There was negligible lipid mobilization after either the placebo or bronchodilator. A slight but insignificant rise in blood glucose was observed after both 30 and 40 µg of clenbuterol.